FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Bowles, HR
AF Bowles, Heather R.
TI Measurement of Active and Sedentary Behaviors: Closing the Gaps in
Self-Report Methods
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Editorial Material
C1 NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Bowles, HR (reprint author), NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
NR 5
TC 20
Z9 20
U1 0
U2 1
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD JAN
PY 2012
VL 9
SU 1
BP S1
EP S4
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 885FR
UT WOS:000299764400001
PM 22287442
ER
PT J
AU Hagstromer, M
Ainsworth, BE
Kwak, L
Bowles, HR
AF Hagstromer, Maria
Ainsworth, Barbara E.
Kwak, Lydia
Bowles, Heather R.
TI A Checklist for Evaluating the Methodological Quality of Validation
Studies on Self-Report Instruments for Physical Activity and Sedentary
Behavior
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE external validity; internal validity; reporting; questionnaire
ID GROUP RANDOMIZED-TRIALS; STATISTICAL-METHODS; ASSESSING AGREEMENT;
UPDATED GUIDELINES; VALIDITY; QUESTIONNAIRES; EPIDEMIOLOGY; STATEMENT;
DESIGN; ADULTS
AB Context: The quality of methodological papers assessing physical activity instruments depends upon the rigor of a study's design. Objectives: We present a checklist to assess key criteria for instrument validation studies. Process: A Medline/PubMed search was performed to identify guidelines for evaluating the methodological quality of instrument validation studies. Based upon the literature, a pilot version of a checklist was developed consisting of 21 items with 3 subscales: 1) quality of the reported data (9 items: assess whether the reported information is sufficient to make an unbiased assessment of the findings); 2) external validity of the results (3 items: assess the extent to which the findings are generalizable); 3) internal validity of the study (9 items: assess the rigor of the study design). The checklist was tested for interrater reliability and feasibility with 6 raters. Findings: Raters viewed the checklist as helpful for reviewing studies. They suggested minor wording changes for 8 items to clarify intent. One item was divided into 2 items for a total of 22 items. Discussion: Checklists may be useful to assess the quality of studies designed to validate physical activity instruments. Future research should test checklist internal consistency, test-retest reliability, and criterion validity.
C1 [Hagstromer, Maria] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
[Ainsworth, Barbara E.] Arizona State Univ, Coll Nursing & Hlth Innovat, Program Exercise & Wellness, Phoenix, AZ USA.
[Kwak, Lydia] Karolinska Inst, Dept Biosci, Huddinge, Sweden.
[Bowles, Heather R.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hagstromer, M (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
NR 31
TC 9
Z9 9
U1 1
U2 6
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD JAN
PY 2012
VL 9
SU 1
BP S29
EP S36
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 885FR
UT WOS:000299764400005
PM 22287445
ER
PT J
AU Troiano, RP
Gabriel, KKP
Welk, GJ
Owen, N
Sternfeld, B
AF Troiano, Richard P.
Gabriel, Kelley K. Pettee
Welk, Gregory J.
Owen, Neville
Sternfeld, Barbara
TI Reported Physical Activity and Sedentary Behavior: Why Do You Ask?
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE self-report; accelerometer; assessment method
ID PUBLIC-HEALTH; RELIABILITY; PREVENTION; VALIDITY; TIME; RISK; TOO
AB Context: Advances in device-based measures have led researchers to question the value of reported measures of physical activity or sedentary behavior. The premise of the Workshop on Measurement of Active and Sedentary Behaviors: Closing the Gaps in Self-Report Methods, held in July 2010, was that assessment of behavior by self-report is a valuable approach. Objective: To provide suggestions to optimize the value of reported physical activity and sedentary behavior, we 1) discuss the constructs that devices and reports of behavior can measure, 2) develop a framework to help guide decision-making about the best approach to physical activity and sedentary behavior assessment in a given situation, and 3) address the potential for combining reported behavior methods with device-based monitoring to enhance both approaches. Process: After participation in a workshop breakout session, coauthors summarized the ideas presented and reached consensus on the material presented here. Conclusions: To select appropriate physical activity assessment methods and correctly interpret the measures obtained, researchers should carefully consider the purpose for assessment, physical activity constructs of interest, characteristics of the population and measurement tool, and the theoretical link between the exposure and outcome of interest.
C1 [Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MA USA.
[Gabriel, Kelley K. Pettee] Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Austin, TX USA.
[Welk, Gregory J.] Iowa State Univ, Dept Hlth & Human Performance, Ames, IA USA.
[Owen, Neville] Univ Queensland, Dept Populat Hlth, Brisbane, Qld, Australia.
[Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA.
RP Troiano, RP (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MA USA.
RI Owen, Neville/K-5986-2012
NR 31
TC 35
Z9 35
U1 1
U2 8
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD JAN
PY 2012
VL 9
SU 1
BP S68
EP S75
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 885FR
UT WOS:000299764400009
PM 22287450
ER
PT J
AU Nelson, RF
AF Nelson, R. F.
TI Glycinergic neurons process images
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Editorial Material
ID AMACRINE CELLS; CONE PATHWAYS; CAT RETINA; FIELD
C1 NINDS, NIH, Basic Neurosci Program, Bethesda, MD 20892 USA.
RP Nelson, RF (reprint author), NINDS, NIH, Basic Neurosci Program, 5625 Fishers Lane,Room TS-09, Bethesda, MD 20892 USA.
EM nelsonr@ninds.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JAN
PY 2012
VL 590
IS 2
BP 239
EP 240
DI 10.1113/jphysiol.2011.224584
PG 2
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 876IS
UT WOS:000299101800002
PM 22247262
ER
PT J
AU Daye, PM
Blohm, G
Lefevre, P
AF Daye, Pierre M.
Blohm, Gunnar
Lefevre, Philippe
TI Target motion direction influence on tracking performance and head
tracking strategies in head-unrestrained conditions
SO JOURNAL OF VISION
LA English
DT Article
DE eye-head coordination; head-free; head-unrestrained; pursuit eye
movements
ID COMPLEX 2-DIMENSIONAL TRAJECTORIES; PREDICTIVE SMOOTH-PURSUIT; FELINE
NECK MUSCLES; FOREL FIELD-H; EYE; MOVEMENTS; COORDINATION; MOTONEURONS;
EXCITATION; ACTIVATION
AB We examined subjects' behavior when they tracked periodic oscillating targets moving along a randomly oriented ramp with the head free to move. This study focuses on the effect of target motion direction on pursuit performance and on head tracking strategies used by human subjects to coordinate eye and head movements. Our analyses revealed that the gaze tracking gain was modulated by both target oscillation frequency and target motion direction. We found that pursuit gain was modulated by the target motion direction: vertical pursuit being less accurate than horizontal pursuit. While gaze tracking was sensitive to target frequency and orientation, head behavior was less modulated by a change of target frequency than by a change of target motion direction. Additionally, subjects had two main strategies for moving their head: They oriented their head to favor rotations around either the head dorsoventral (target motion directions <20 deg) or mediolateral axis (target motion directions >70 deg). In between, the subjects did not choose a consistent rotation axis for identical target motion directions.
C1 [Daye, Pierre M.] NEI, Lab Sensimotor Res, NIH, Bethesda, MD 20892 USA.
[Daye, Pierre M.; Lefevre, Philippe] Catholic Univ Louvain, ICTEAM, B-1348 Louvain, Belgium.
[Daye, Pierre M.; Lefevre, Philippe] Catholic Univ Louvain, IoNS, B-1200 Brussels, Belgium.
[Blohm, Gunnar] Queens Univ, Ctr Neurosci Studies, Kingston, ON, Canada.
RP Daye, PM (reprint author), NEI, Lab Sensimotor Res, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA.
EM pierre.daye@gmail.com
FU Fonds National de la Recherche Scientifique, Action de Recherche
Concertee (Belgium); Belgian State, Science Policy Office; NSERC
(Canada); ORF (Canada); CFI (Canada); Botterell Foundation (Queen's
University, Kingston, ON, Canada); National Eye Institute, NIH, DHHS
FX Support for this work was provided by Fonds National de la Recherche
Scientifique, Action de Recherche Concertee (Belgium). This paper
presents research results of the Belgian Network Dynamical Systems,
Control and Optimization, funded by the Interuniversity Attraction Poles
Programmes, initiated by the Belgian State, Science Policy Office. This
work has been supported by NSERC (Canada), ORF (Canada), CFI (Canada)
and the Botterell Foundation (Queen's University, Kingston, ON, Canada).
One of the authors (PMD) was supported in part by the intramural
research program of the National Eye Institute, NIH, DHHS.
NR 22
TC 3
Z9 3
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 1534-7362
J9 J VISION
JI J. Vision
PY 2012
VL 12
IS 1
AR 23
DI 10.1167/12.1.23
PG 12
WC Ophthalmology
SC Ophthalmology
GA 884TN
UT WOS:000299731800023
ER
PT J
AU Ferrucci, L
de Cabo, R
Knuth, ND
Studenski, S
AF Ferrucci, Luigi
de Cabo, Rafa
Knuth, Nicolas D.
Studenski, Stephanie
TI Of Greek Heroes, Wiggling Worms, Mighty Mice, and Old Body Builders
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID MUSCLE STRENGTH; SKELETAL-MUSCLE; MASS; HEALTH; SARCOPENIA; WOMEN;
PREDICTORS; DISABILITY; MOBILITY; QUALITY
C1 [Ferrucci, Luigi] NIA, Clin Res Branch, Clin Unit, Harbor Hosp,NIH, Baltimore, MD 21225 USA.
[Studenski, Stephanie] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA.
RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Clin Unit, Harbor Hosp,NIH, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU Intramural NIH HHS; NIA NIH HHS [P30 AG024827]
NR 22
TC 10
Z9 11
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 JAN
PY 2012
VL 67
IS 1
BP 13
EP 16
DI 10.1093/gerona/glr046
PG 4
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 885PQ
UT WOS:000299791700002
PM 22113943
ER
PT J
AU Hicks, GE
Shardell, M
Alley, DE
Miller, RR
Bandinelli, S
Guralnik, J
Lauretani, F
Simonsick, EM
Ferrucci, L
AF Hicks, Gregory E.
Shardell, Michelle
Alley, Dawn E.
Miller, Ram R.
Bandinelli, Stefania
Guralnik, Jack
Lauretani, Fulvio
Simonsick, Eleanor M.
Ferrucci, Luigi
TI Absolute Strength and Loss of Strength as Predictors of Mobility Decline
in Older Adults: The InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Strength; Sarcopenia; Mobility decline
ID MUSCLE STRENGTH; PHYSICAL-DISABILITY; MUSCULAR STRENGTH; MEANINGFUL
CHANGE; SARCOPENIA; RELIABILITY; PERFORMANCE; WOMEN; MASS; MEN
AB Theoretical definitions of sarcopenia traditionally emphasize age-related loss of muscle strength; however, most analyses of the association between strength and mobility examine strength at a single time point. This study sought to identify sex-specific cutpoints for muscle strength and power (at one time point) and 3-year changes in strength and power that would maximize prediction of 3-year mobility decline.
Longitudinal analysis of 934 adults aged >= 65 years enrolled in the Invecchiare in Chianti study was conducted. Grip strength, knee extension strength, and lower extremity power were measured at baseline and 3 years postenrollment. Mobility function (gait speed and self-reported mobility disability) was measured at 3 and 6 years postenrollment. Classification and regression tree analysis was used to predict mobility decline from Years 3 to 6.
Men with knee extension strength < 19.2 kg and grip strength < 39.0 kg had clinically meaningful declines in gait speed of .24 m/s. Furthermore, men with power < 105 W were nearly nine times more likely to develop incident mobility disability (likelihood ratio = 8.68; 95% confidence interval = 3.91, 19.44). Among women, knee extension strength < 18.0 kg was associated with a minimal gait speed decline of 0.06 m/s, and women with leg power < 64 W were three times more likely to develop incident mobility disability (likelihood ratio = 3.01; 95% confidence interval = 1.79, 5.08). Three-year changes in strength and power did not predict mobility decline in either sex.
Findings suggest that strength and power measured at one time point are more predictive of mobility decline than 3-year changes and that low strength and power are particularly powerful risk factors in men.
C1 [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
[Hicks, Gregory E.; Shardell, Michelle; Alley, Dawn E.; Miller, Ram R.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Gerontol, Baltimore, MD 21201 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Rehabil Dept, Geriatr Unit, Parma, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Rehabil Dept, Lab Movement Anal, Parma, Italy.
[Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Simonsick, Eleanor M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
RP Hicks, GE (reprint author), Univ Delaware, Dept Phys Therapy, 313 McKinly Lab, Newark, DE 19716 USA.
EM ghicks@udel.edu
RI Lauretani, Fulvio/K-5115-2016
OI Lauretani, Fulvio/0000-0002-5287-9972
FU Italian Ministry of Health; U.S. National Institute on Aging [263 MD
916413, 263 MD 821336]; National Institutes of Health [K23 AG019161];
[R21HD057274]; [K12 HD043489]; [R01 AG029315]
FX The InCHIANTI study was supported by the Italian Ministry of Health and
in part by the U.S. National Institute on Aging (contracts 263 MD 916413
and 263 MD 821336). Dr. G. E. H. was supported by grant R21HD057274, Dr.
D. E. A. was supported by grant K12 HD043489, Dr. M. S. was supported by
grant R01 AG029315, and Dr. R. M. M. was supported by grant K23 AG019161
from the National Institutes of Health.
NR 34
TC 61
Z9 66
U1 3
U2 20
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 JAN
PY 2012
VL 67
IS 1
BP 66
EP 73
DI 10.1093/gerona/glr055
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 885PQ
UT WOS:000299791700008
PM 21546582
ER
PT J
AU Kalyani, RR
Metter, EJ
Ramachandran, R
Chia, CW
Saudek, CD
Ferrucci, L
AF Kalyani, Rita R.
Metter, E. Jeffrey
Ramachandran, Ramona
Chia, Chee W.
Saudek, Christopher D.
Ferrucci, Luigi
TI Glucose and Insulin Measurements From the Oral Glucose Tolerance Test
and Relationship to Muscle Mass
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Glucose; Insulin; Muscle; Older adults
ID SKELETAL-MUSCLE; BODY-COMPOSITION; OLDER-ADULTS; COMPUTED-TOMOGRAPHY;
PHYSICAL ACTIVITIES; STRENGTH; HEALTH; DISABILITY; WOMEN; COMORBIDITIES
AB Diabetes is associated with decreased muscle mass. The effect of higher levels of glucose and insulin on muscle mass has not been studied in individuals without diabetes. We sought to determine the relationship of insulin and glucose measurements from the oral glucose tolerance test (OGTT) with muscle mass in persons without diabetes.
We analyzed data from 587 participants in the Baltimore Longitudinal Study of Aging (mean age 67.3 years, range 26-95 years) without diabetes who underwent a 2-hour OGTT, including glucose and insulin measurements taken every 20 minutes and assessment of midthigh muscle cross-sectional area by computed tomography, taken as a proxy measure of muscle mass. Linear regression models and Bayesian model averaging were used to explore the independent cross-sectional association of various OGTT-derived measures and midthigh muscle cross-sectional area, independent of confounders.
Individually, fasting glucose, fasting insulin, OGTT glucose (40, 60, 80, 100, and 120 minutes), OGTT insulin (20, 60, 80, 100, and 120 minutes), homeostasis model assessment of insulin resistance, integrated glucose area, and integrated insulin area were inversely associated, and the Matsuda index was positively associated, with the midthigh muscle cross-sectional area (standardized to body weight) after adjustment for age, sex, race, height, physical activity, and peroneal motor nerve conduction velocity (all ps <.05). When considered together, the Matsuda index and fasting glucose were the strongest predictors of lower midthigh muscle cross-sectional area after covariate adjustment.
Higher fasting and OGTT values of both glucose and insulin are associated with lower muscle mass. Longitudinal studies are needed to verify whether individuals free of diabetes that have higher glucose and insulin during an OGTT are at risk for accelerated muscle mass decline with aging.
C1 [Kalyani, Rita R.; Saudek, Christopher D.] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA.
[Metter, E. Jeffrey; Ramachandran, Ramona; Chia, Chee W.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP Kalyani, RR (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA.
EM rrastogi@jhmi.edu
FU National Institute on Aging, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 30
TC 19
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JAN
PY 2012
VL 67
IS 1
BP 74
EP 81
DI 10.1093/gerona/glr022
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 885PQ
UT WOS:000299791700009
PM 21350243
ER
PT J
AU Miki, M
Ball, DW
Linnoila, RI
AF Miki, Makoto
Ball, Douglas W.
Linnoila, R. Ilona
TI Insights into the achaete-scute homolog-1 gene (hASH1) in normal and
neoplastic human lung
SO LUNG CANCER
LA English
DT Article
DE Achaete-scute homolog-1; Synaptophysin; Neuroendocrine; Lung
development; Lung carcinogenesis; Small cell lung cancer; Non-small cell
lung cancer; Human
ID HELIX TRANSCRIPTION FACTORS; NEUROENDOCRINE DIFFERENTIATION;
CELL-POPULATIONS; CANCER; EXPRESSION; CARCINOMAS; MASH1; CHEMOTHERAPY;
ENDOCRINE; FEATURES
AB Achaete-scute homolog-1 (ASH1) is pivotal for the development of pulmonary neuroendocrine (NE) cells. We examined human ASH1 (hASH1) expression across a comprehensive panel of human lung cancer cell lines, primary human lung tumors and normal fetal and post-natal lungs. While hASH1 was a cardinal feature of NE carcinomas, a subgroup of non-NE lung cancers also exhibited expression of this factor. Twenty lung cancer cell lines out of 33 were positive for hASH1 mRNA by reverse transcription PCR, including 6/6 small cell carcinomas (SCLC), 5/5 carcinoids, 6/7 non-SCLC with NE features, and 3/14 other non-SCLC. Among human primary tumors, 2/2 SCLC, 5/5 pulmonary carcinoids. and 10/41 non-SCLC (only 4 of which had NE features) were positive for hASH1 by immunohistochemistry and RNA-RNA in situ hybridization. In normal human fetal lung, the expression of hASH1 and the neural marker synaptophysin was highly concordant in neuroepithelial bodies and solitary NE cells, while the rest of the epithelium was negative. In childhood and adulthood, the markers became progressively discordant, with a majority of hASH1-immunoreactive foci (69%) being negative for synaptophysin in adults, potentially representing dormant NE cell progenitors. We conclude that hASH1 provides an early indication of NE program in human lung. Published by Elsevier Ireland Ltd.
C1 [Miki, Makoto; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ball, Douglas W.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21231 USA.
[Ball, Douglas W.] Johns Hopkins Med Inst, Ctr Oncol, Baltimore, MD 21231 USA.
RP Linnoila, RI (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr,Bg 37,Room 1056B, Bethesda, MD 20850 USA.
EM linnoila@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Drs. Michael Birrer and Eva Szabo for stimulating and critical
discussions of this work, and Sandy Jensen and Dr. Mae Jean Miller for
technical assistance. This work was funded by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 37
TC 19
Z9 21
U1 0
U2 0
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 JAN
PY 2012
VL 75
IS 1
BP 58
EP 65
DI 10.1016/j.lungcan.2011.05.019
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 881AB
UT WOS:000299450600008
PM 21684625
ER
PT J
AU Malley, JD
Kruppa, J
Dasgupta, A
Malley, KG
Ziegler, A
AF Malley, J. D.
Kruppa, J.
Dasgupta, A.
Malley, K. G.
Ziegler, A.
TI Probability Machines Consistent Probability Estimation Using
Nonparametric Learning Machines
SO METHODS OF INFORMATION IN MEDICINE
LA English
DT Article
DE Brier score; consistency; random forest; k nearest neighbor; logistic
regression; probability estimation
ID NEAREST-NEIGHBOR ESTIMATE; LOGISTIC-REGRESSION; STATISTICAL VIEW; RANDOM
FORESTS; CLASSIFICATION; CONVERGENCE; PREDICTION; NETWORK
AB Background: Most machine learning approaches only provide a classification for binary responses. However, probabilities are required for risk estimation using individual patient characteristics. It has been shown recently that every statistical learning machine known to be consistent for a nonparametric regression problem is a probability machine that is provably consistent for this estimation problem.
Objectives: The aim of this paper is to show how random forests and nearest neighbors can be used for consistent estimation of individual probabilities.
Methods: Two random forest algorithms and two nearest neighbor algorithms are described in detail for estimation of individual probabilities. We discuss the consistency of random forests, nearest neighbors and other learning machines in detail. We conduct a simulation study to illustrate the validity of the methods. We exemplify the algorithms by analyzing two well-known data sets on the diagnosis of appendicitis and the diagnosis of diabetes in Pima Indians.
Results: Simulations demonstrate the validity of the method. With the real data application, we show the accuracy and practicality of this approach. We provide sample code from R packages in which the probability estimation is already available. This means that all calculations can be performed using existing software.
Conclusions: Random forest algorithms as well as nearest neighbor approaches are valid machine learning methods for estimating individual probabilities for binary responses. Freely available implementations are available in R and may be used for applications.
C1 [Kruppa, J.; Ziegler, A.] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
[Malley, J. D.] NIH, Ctr Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Dasgupta, A.] NIAMSD, Clin Sci Sect, NIH, Bethesda, MD 20892 USA.
[Malley, K. G.] Malley Res Programming, Rockville, MD USA.
RP Ziegler, A (reprint author), Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck,Maria Goeppert Str 1, D-23562 Lubeck, Germany.
EM ziegler@imbs.uni-luebeck.de
OI Ziegler, Andreas/0000-0002-8386-5397
FU European Union (ENGAGE) [201413]; German Ministry of Research and
Education [01GS0831]; intramural funding of the University of Lubeck;
National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Center for Information Technology, National Institutes of Health, USA
FX The authors are extremely grateful to Joan Bailey-Wilson and Gerard Biau
for valuable discussions and to Sholom M. Weiss for making the
appendicitis data available. Funding: AZ and JK are supported by the
European Union (ENGAGE, 201413), the German Ministry of Research and
Education (01GS0831) and intramural funding of the University of Lubeck.
This work was partly supported by the Intramural Research Programs of
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (AD) and the Center for Information Technology (JDM), National
Institutes of Health, USA.
NR 36
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PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0026-1270
J9 METHOD INFORM MED
JI Methods Inf. Med.
PY 2012
VL 51
IS 1
BP 74
EP 81
DI 10.3414/ME00-01-0052
PG 8
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA 887DS
UT WOS:000299907700010
PM 21915433
ER
PT J
AU Marshall, RS
Festa, JR
Cheung, YK
Chen, R
Pavol, MA
Derdeyn, CP
Clarke, WR
Videen, TO
Grubb, RL
Adams, HP
Powers, WJ
Lazar, RM
AF Marshall, R. S.
Festa, J. R.
Cheung, Y. K.
Chen, R.
Pavol, M. A.
Derdeyn, C. P.
Clarke, W. R.
Videen, T. O.
Grubb, R. L.
Adams, H. P.
Powers, W. J.
Lazar, R. M.
TI Cerebral hemodynamics and cognitive impairment Baseline data from the
RECON trial
SO NEUROLOGY
LA English
DT Article
ID CAROTID-ARTERY OCCLUSION; POSITRON-EMISSION-TOMOGRAPHY; TRANSIENT
ISCHEMIC ATTACKS; IC BYPASS-SURGERY; CEREBROVASCULAR-DISEASE;
PERFORMANCE; STENOSIS; AGE; ENDARTERECTOMY; INFARCTION
AB Objective: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON).
Methods: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio > 1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or <= 1.13, stratifying by TIA vs stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests.
Results: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs -0.76, p = 0.040). Older age and right ICA side were also significant in this model.
Conclusion: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested. Neurology (R) 2012; 78:250-255
C1 [Marshall, R. S.; Festa, J. R.; Cheung, Y. K.; Chen, R.; Pavol, M. A.; Lazar, R. M.] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Derdeyn, C. P.; Videen, T. O.; Grubb, R. L.] Washington Univ, St Louis, MO USA.
[Clarke, W. R.; Adams, H. P.] Univ Iowa, Ames, IA USA.
[Cheung, Y. K.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Powers, W. J.] Univ N Carolina, Chapel Hill, NC USA.
RP Marshall, RS (reprint author), Columbia Univ, Med Ctr, New York, NY 10027 USA.
EM rsm2@columbia.edu
RI Chen, Robert/B-3899-2009;
OI Chen, Robert/0000-0002-8371-8629; Derdeyn, Colin/0000-0002-5932-2683
FU NINDS [NS048212, NS42167, 5U01NS041895]; Richard and Jenny Levine
Research Fund; NIH/NINDS; NIH (NINDS/NICHD/NHLBI); Terumo Heart, Inc.;
EvaHeart Medical USA, Inc.; NIH (NIAMS/NINDS/NIDDK); Michael J. Fox
Foundation; Barnes-Jewish Hospital Foundation; NIH (NINDS/NIAMS); NIH
(NHLBI/NINDS/NICHD)
FX Supported by NINDS NS048212 (R.S.M.), NS42167 (W.J.P.), and 5U01NS041895
(W.R.C.) and by The Richard and Jenny Levine Research Fund.; Dr.
Marshall has a patent pending re: a novel use of a drug for post-stroke
dystonia; receives publishing royalties for OnCall Neurology (Elsevier,
2003-present); has received speaker honoraria from Ferrer International;
and receives research support from the NIH/NINDS. Dr. Festa receives
research support from the NIH (NINDS/NICHD/NHLBI). Dr. Cheung serves on
the editorial board of Biometrics; receives publishing royalties for
Dose Finding by the Continual Reassessment Method (Chapman and Hall/CRC,
2011); serves as a consultant for Remedy and Estee Lauder; and receives
research from the NIH/NINDS. R. Chen receives research support from the
NIH/NINDS. Dr. Pavol receives research support from Terumo Heart, Inc.,
EvaHeart Medical USA, Inc., and the NIH/NINDS. Dr. Derdeyn serves on a
scientific advisory boards for W. L. Gore and Associates and the
NIH/NINDS; serves on the editorial boards of Stroke and the American
Journal of Neuroradiology; is listed on patents re: a system for
surgical repair of intracranial aneurysms and a method to stimulate
peripheral nerves; receives research support from the NIH/NINDS; and
holds stock options in nFocus, Inc. Dr. Clarke receives publishing
royalties for Statistical Methods for the Analysis of Biomedical Data,
2nd edition (Wiley-Interscience, 2002) and receives research support
from the NIH (NIAMS/NINDS/NIDDK). Dr. Videen receives research support
from the NIH/NINDS and the Michael J. Fox Foundation. Dr. Grubb serves
on the editorial board of the Journal of Neurosurgery and receives
research support from the NIH/NINDS and the Barnes-Jewish Hospital
Foundation. Dr. Adams serves on scientific advisory boards for
Medtronic, Inc. and Merck Serono; serves on the editorial boards of
Stroke, Journal of Stroke and Cerebrovascular Diseases, and
Cerebrovascular Diseases; receives publishing royalties for Handbook of
Cerebrovascular Diseases, 2nd edition (Informa Healthcare, 2004) and
Principles of Cerebrovascular Disease (McGraw-Hill Professional, 2006);
and receives research support from the NIH/NINDS. Dr. Powers serves on a
scientific advisory board for the NIH Morehouse School of Medicine;
serves on the editorial boards of Stroke and Journal of Cerebral Blood
Flow and Metabolism; and receives research support from the NIH
(NINDS/NIAMS). Dr. Lazar serves on the editorial board of Stroke and
receives research support from the NIH (NHLBI/NINDS/NICHD).
NR 36
TC 32
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U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JAN
PY 2012
VL 78
IS 4
BP 250
EP 255
DI 10.1212/WNL.0b013e31824365d3
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 885OB
UT WOS:000299787200008
PM 22238418
ER
PT J
AU Canuto, HC
Fishbein, KW
Huang, A
Doty, SB
Herbert, RA
Peckham, J
Pleshko, N
Spencer, RG
AF Canuto, H. C.
Fishbein, K. W.
Huang, A.
Doty, S. B.
Herbert, R. A.
Peckham, J.
Pleshko, N.
Spencer, R. G.
TI Characterization of skin abnormalities in a mouse model of osteogenesis
imperfecta using high resolution magnetic resonance imaging and Fourier
transform infrared imaging spectroscopy
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRI; Skin; Osteogenesis Imperfecta; FT-IR; Mouse Model
ID COLLAGEN MUTATION DATABASE; IN-VIVO; ARTICULAR-CARTILAGE;
CONNECTIVE-TISSUE; RELAXATION-TIMES; CHILD-ABUSE; MECHANICAL-PROPERTIES;
HYDRATED COLLAGEN; MR MICROSCOPY; GOAT KNEE
AB Evaluation of the skin phenotype in osteogenesis imperfecta (OI) typically involves biochemical measurements, such as histologic or biochemical assessment of the collagen produced from biopsy-derived dermal fibroblasts. As an alternative, the current study utilized non-invasive magnetic resonance imaging (MRI) microscopy and optical spectroscopy to define biophysical characteristics of skin in an animal model of OI. MRI of skin harvested from control, homozygous oim/oim and heterozygous oim/+ mice demonstrated several differences in anatomic and biophysical properties. Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to interpret observed MRI signal characteristics in terms of chemical composition. Differences between wild-type and OI mouse skin included the appearance of a collagen-depleted lower dermal layer containing prominent hair follicles in the oim/oim mice, accounting for 55% of skin thickness in these. The MRI magnetization transfer rate was lower by 50% in this layer as compared to the upper dermis, consistent with lower collagen content. The MRI transverse relaxation time, T2, was greater by 30% in the dermis of the oim/oim mice compared to controls, consistent with a more highly hydrated collagen network. Similarly, an FT-IRIS-defined measure of collagen integrity was 30% lower in the oim/oim mice. We conclude that characterization of phenotypic differences between the skin of OI and wild-type mice by MRI and FT-IRIS is feasible, and that these techniques provide powerful complementary approaches for the analysis of the skin phenotype in animal models of disease. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Canuto, H. C.; Fishbein, K. W.; Spencer, R. G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Huang, A.; Doty, S. B.; Pleshko, N.] Hosp Special Surg, New York, NY 10021 USA.
[Herbert, R. A.; Peckham, J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Pleshko, N.] Temple Univ, Dept Mech Engn, Philadelphia, PA 19122 USA.
RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, Intramural Res Program, GRC 4D-06 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
RI Huang, Alice/L-2256-2015;
OI Huang, Alice/0000-0002-5037-6829; Fishbein, Kenneth/0000-0002-6353-4603
FU NIH, National Institute on Aging; NIH [AR48337]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging and NIH grant AR48337 (NP).
NR 61
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U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD JAN
PY 2012
VL 25
IS 1
BP 169
EP 176
DI 10.1002/nbm.1732
PG 8
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 875ZF
UT WOS:000299074600019
PM 21845737
ER
PT J
AU Bulut, G
Hong, SH
Chen, K
Beauchamp, EM
Rahim, S
Kosturko, GW
Glasgow, E
Dakshanamurthy, S
Lee, HS
Daar, I
Toretsky, JA
Khanna, C
Uren, A
AF Bulut, G.
Hong, S-H
Chen, K.
Beauchamp, E. M.
Rahim, S.
Kosturko, G. W.
Glasgow, E.
Dakshanamurthy, S.
Lee, H-S
Daar, I.
Toretsky, J. A.
Khanna, C.
Ueren, A.
TI Small molecule inhibitors of ezrin inhibit the invasive phenotype of
osteosarcoma cells
SO ONCOGENE
LA English
DT Article
DE ezrin; osteosarcoma; metastasis; small molecule screening; drug
discovery
ID ERM PROTEINS; OSTEOGENIC-SARCOMA; PLASMA-MEMBRANE; BINDING-SITE; LINKER
EZRIN; METASTASIS; EXPRESSION; SURVIVAL; IDENTIFICATION; CHEMOTHERAPY
AB Ezrin is a multifunctional protein that connects the actin cytoskeleton to the extracellular matrix through transmembrane proteins. High ezrin expression is associated with lung metastasis and poor survival in cancer. We screened small molecule libraries for compounds that directly interact with ezrin protein using surface plasmon resonance to identify lead compounds. The secondary functional assays used for lead compound selection included ezrin phosphorylation as measured by immunoprecipitation and in vitro kinase assays, actin binding, chemotaxis, invasion into an endothelial cell monolayer, zebrafish and Xenopus embryonic development, mouse lung organ culture and an in vivo lung metastasis model. Two molecules, NSC305787 and NSC668394, that directly bind to ezrin with low micromolar affinity were selected based on inhibition of ezrin function in multiple assays. They inhibited ezrin phosphorylation, ezrin-actin interaction and ezrin-mediated motility of osteosarcoma (OS) cells in culture. NSC305787 mimicked the ezrin morpholino phenotype, and NSC668394 caused a unique developmental defect consistent with reduced cell motility in zebrafish. Following tail vein injection of OS cells into mice, both molecules inhibited lung metastasis of ezrinsensitive cells, but not ezrin-resistant cells. The small molecule inhibitors NSC305787 and NSC668394 demonstrate a novel targeted therapy that directly inhibits ezrin protein as an approach to prevent tumor metastasis. Oncogene (2012) 31, 269-281; doi:10.1038/onc.2011.245; published online 27 June 2011
C1 [Ueren, A.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, NRB, Washington, DC 20057 USA.
[Hong, S-H; Khanna, C.] NCI, Tumor & Metastasis Biol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lee, H-S; Daar, I.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
RP Uren, A (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, NRB, 3970 Reservoir Rd NW,Room E312, Washington, DC 20057 USA.
EM au26@georgetown.edu
RI BULUT, GULAY/J-3180-2012; Lee, Hyun-Shik/G-3555-2011;
OI Glasgow, Eric/0000-0001-7729-3954; Daar, Ira/0000-0003-2657-526X
FU Children's Cancer Foundation of Baltimore; US Department of Defense
[W81XWH-10-1-0137]; Brandon Carrington Lee Foundation; Go4theGoal;
Dani's Foundation; Alex's Lemonade Stand Foundation; Liddy Shriver
Sarcoma Initiative; Burroughs Wellcome Clinical Scientist Award in
Translational Research; NIH [R01CA133662, R01CA138212]; Cancer Center
[P30 CA051008]
FX Support for our work came from the Children's Cancer Foundation of
Baltimore (AU), US Department of Defense (W81XWH-10-1-0137, AU), Brandon
Carrington Lee Foundation (G.K., AU), Go4theGoal, Dani's Foundation,
Alex's Lemonade Stand Foundation, Liddy Shriver Sarcoma Initiative,
Burroughs Wellcome Clinical Scientist Award in Translational Research
(JT), and the NIH R01CA133662 (JT), R01CA138212 (JT) and Cancer Center
Support Grant P30 CA051008 for use of Biacore Molecular Interaction
Shared Resource. We would like to thank to Dr Anthony Bretscher (Cornell
University) for providing the WT Ezrin construct, Developmental
Therapeutics Program, NCI for providing the small molecule libraries.
NR 44
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U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2012
VL 31
IS 3
BP 269
EP 281
DI 10.1038/onc.2011.245
PG 13
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 882DQ
UT WOS:000299542100001
PM 21706056
ER
PT J
AU Lai, C
Roschewski, M
AF Lai, Catherine
Roschewski, Mark
TI Nodal Marginal Zone Lymphoma: Impersonalized Medicine THE
TRAVERSE-GLEHEN ET AL ARTICLE REVIEWED
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID B-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; RITUXIMAB; THERAPY; TRIAL
C1 [Lai, Catherine] NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA.
[Roschewski, Mark] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
RP Lai, C (reprint author), NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA.
NR 19
TC 1
Z9 1
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JAN
PY 2012
VL 26
IS 1
BP 104
EP +
PG 3
WC Oncology
SC Oncology
GA 883UB
UT WOS:000299659300013
PM 22393803
ER
PT J
AU Chewning, B
Bylund, CL
Shah, B
Arora, NK
Gueguen, JA
Makoul, G
AF Chewning, Betty
Bylund, Carma L.
Shah, Bupendra
Arora, Neeraj K.
Gueguen, Jennifer A.
Makoul, Gregory
TI Patient preferences for shared decisions: A systematic review
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Review
DE Shared decision making; Patient preferences; Patient decisions
ID CANCER-PATIENTS PREFERENCES; BREAST-CANCER; INFORMATION NEEDS;
HEALTH-CARE; PROSTATE-CANCER; MAKING PREFERENCES; PARTICIPATION
PREFERENCES; PHYSICIAN PERCEPTIONS; PROFESSIONAL CARERS;
COLORECTAL-CANCER
AB Objectives: Empirical literature on patient decision role preferences regarding treatment and screening was reviewed to summarize patients' role preferences across measures, time and patient population.
Methods: Five databases were searched from January 1980 to December 2007 (1980-2007 Ovid
MEDLINE, Cochrane Database of Systematic Reviews, PsychInfo, Web of Science and PubMed (2005-2007)). Eligible studies measured patient decision role preferences, described measures, presented findings as percentages or mean scores and were published in English from any country. Studies were compared by patient population, time of publication, and measure.
Results: 115 studies were eligible. The majority of patients preferred sharing decisions with physicians in 63% of the studies. A time trend appeared. The majority of respondents preferred sharing decision roles in 71% of the studies from 2000 and later, compared to 50% of studies before 2000. Measures themselves, in addition to patient population, influenced the preferred decision roles reported.
Conclusion: Findings appear to vary with the measure of preferred decision making used, time of the publication and characteristics of the population.
Practice implications: The role preference measure itself must be considered when interpreting patient responses to a measure or question about a patient's preference for decision roles. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Chewning, Betty] Univ Wisconsin, Sch Pharm, Sonderegger Res Ctr, Madison, WI 53705 USA.
[Bylund, Carma L.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY USA.
[Shah, Bupendra] Arnold & Marie Schwartz Coll Pharm, Div Pharmaceut Sci, Brooklyn, NY USA.
[Arora, Neeraj K.] NCI, Outcomes Res Branch, ARP, DCCPS, Bethesda, MD 20892 USA.
[Gueguen, Jennifer A.] Mem Sloan Kettering Canc Ctr, Integrat Med Serv, New York, NY USA.
[Makoul, Gregory] Univ Connecticut, Sch Med, St Francis Hosp & Med Ctr, Storrs, CT USA.
RP Chewning, B (reprint author), Univ Wisconsin, Sch Pharm, Sonderegger Res Ctr, 777 Highland Ave, Madison, WI 53705 USA.
EM bachewning@pharmacy.wisc.edu
FU NIA NIH HHS [R01 AG018362]
NR 140
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U1 11
U2 60
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 JAN
PY 2012
VL 86
IS 1
BP 9
EP 18
DI 10.1016/j.pec.2011.02.004
PG 10
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 882RW
UT WOS:000299582600003
PM 21474265
ER
PT J
AU Han, PKJ
Klein, WMP
Killam, B
Lehman, T
Massett, H
Freedman, AN
AF Han, Paul K. J.
Klein, William M. P.
Killam, Bill
Lehman, Tom
Massett, Holly
Freedman, Andrew N.
TI Representing randomness in the communication of individualized cancer
risk estimates: Effects on cancer risk perceptions, worry, and
subjective uncertainty about risk
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Risk communication; Uncertainty; Randomness; Cancer
ID BREAST-CANCER; DECISION-MAKING; PROBABILITY; MODELS; INDEX; WOMEN
AB Objective: To test the effect of novel representations of randomness on risk perceptions, worry, and subjective uncertainty about individualized colorectal cancer risk estimates.
Methods: A web-based factorial experiment was conducted, in which 225 adults aged 40 years and older were provided with hypothetical individualized colorectal cancer risk estimates, using 5 different textual and visual representations varying in expressed randomness. Outcome measures were perceived cancer risk, cancer worry, and subjective uncertainty about cancer risk: the moderating effect of dispositional optimism was also examined.
Results: Representational format was significantly associated with subjective uncertainty about cancer risk, but not with perceived cancer risk or worry. A format using software-based animation to express randomness dynamically led to the highest subjective uncertainty, although a static visual non-random format also increased uncertainty. Dispositional optimism moderated this effect: between-format differences in uncertainty were significant only for participants with low optimism.
Conclusion: Representing randomness in individualized estimates of cancer risk increases subjective uncertainty about risk. A novel dynamic visual format produces the greatest effect, which is moderated by individual differences in optimism.
Practice implications: Novel representations of randomness may be effective in improving people's understanding of the essential uncertainty pertaining to individualized cancer risk estimates. Published by Elsevier Ireland Ltd.
C1 [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04105 USA.
[Klein, William M. P.; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Killam, Bill] User Ctr Design, Ashburn, VA 20147 USA.
[Lehman, Tom] Acad Educ Dev, Ctr Social Mkt & Behav Change, Washington, DC USA.
[Massett, Holly] NCI, Off Market Res & Evaluat, Bethesda, MD 20892 USA.
RP Han, PKJ (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 39 Forest Ave, Portland, ME 04105 USA.
EM hanp@mmc.org
OI Han, Paul/0000-0003-0165-1940
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 17
Z9 17
U1 1
U2 8
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 JAN
PY 2012
VL 86
IS 1
BP 106
EP 113
DI 10.1016/j.pec.2011.01.033
PG 8
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 882RW
UT WOS:000299582600016
PM 21377311
ER
PT J
AU Schloesser, RJ
Martinowich, K
Manji, HK
AF Schloesser, Robert J.
Martinowich, Keri
Manji, Husseini K.
TI Mood-stabilizing drugs: mechanisms of action
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
DE bipolar disorder; mood-stabilizing drugs; neurotrophic factors; synaptic
plasticity; mania; lithium
ID BIPOLAR DISORDER PATIENTS; DEEP BRAIN-STIMULATION; GRAY-MATTER VOLUME;
TREATMENT-RESISTANT DEPRESSION; ANTIDEPRESSANT-INDUCED MANIA;
NEONATAL-RAT HIPPOCAMPUS; LITHIUM-TREATED PATIENTS; NMDA RECEPTOR
BLOCKADE; D-ASPARTATE ANTAGONIST; MAJOR DEPRESSION
AB Mood-stabilizing drugs are the most widely prescribed pharmacological treatments for bipolar disorder, a disease characterized by recurrent episodes of mania and depression. Despite extensive clinical utilization, significant questions concerning their mechanisms of action remain. In recent years, a diverse set of molecular and cellular targets of these drugs has been identified. Based on these findings, downstream effects on neural and synaptic plasticity within key circuits have been proposed. Here, we discuss recent data, identify current challenges impeding progress and define areas for future investigation. Further understanding of the primary targets and downstream levels of convergence of mood-stabilizing drugs will guide development of novel therapeutic strategies and help translate discoveries into more effective treatments with less burdensome adverse-effect profiles.
C1 [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ 08560 USA.
[Schloesser, Robert J.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Martinowich, Keri] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA.
RP Manji, HK (reprint author), Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ 08560 USA.
EM HManji@its.jnj.com
RI Martinowich, Keri/F-9841-2012;
OI Martinowich, Keri/0000-0002-5237-0789
FU National Institute of Mental Health
FX Support was provided by the National Institute of Mental Health
Intramural Research Program. The figures and illustrations were designed
and created by Anne K. Schlosser.
NR 133
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U1 4
U2 21
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD JAN
PY 2012
VL 35
IS 1
SI SI
BP 36
EP 46
DI 10.1016/j.tins.2011.11.009
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 884MU
UT WOS:000299713000005
PM 22217451
ER
PT J
AU Fontes, JD
Lyass, A
Massaro, JM
Rienstra, M
Dallmeier, D
Schnabel, RB
Wang, TJ
Vasan, RS
Lubitz, SA
Magnani, JW
Levy, D
Ellinor, PT
Fox, CS
Benjamin, EJ
AF Fontes, Joao D.
Lyass, Asya
Massaro, Joseph M.
Rienstra, Michiel
Dallmeier, Dhayana
Schnabel, Renate B.
Wang, Thomas J.
Vasan, Ramachandran S.
Lubitz, Steven A.
Magnani, Jared W.
Levy, Daniel
Ellinor, Patrick T.
Fox, Caroline S.
Benjamin, Emelia J.
TI Insulin Resistance and Atrial Fibrillation (from the Framingham Heart
Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID METABOLIC SYNDROME; DIABETES-MELLITUS; RISK; ATHEROSCLEROSIS;
ASSOCIATION; DISEASE; COHORT; MEN
AB Diabetes mellitus and obesity are increasing in prevalence and are associated with an elevated risk of atrial fibrillation (AF). Given the aging of the United States population, AF is projected to concomitantly increase in prevalence in the upcoming decades. Both diabetes and obesity are associated with insulin resistance. Whether insulin resistance is an intermediate step for the development of AF is uncertain. We hypothesized that insulin resistance is associated with an increased risk of incident AF. We examined the association of insulin resistance with incident AF using multivariate Cox proportional hazards regression analysis adjusting for the established AF risk factors (i.e., age, gender, systolic blood pressure, hypertension treatment, PR interval, significant heart murmur, heart failure, and body mass index). Of the 3,023 eligible participants (55% women; mean age 59 years) representing 4,583 person-examinations (Framingham Offspring fifth and seventh examination cycles), 279 participants developed AF (9.3%) within <= 10 years of follow-up. With multivariate modeling, insulin resistance was not significantly associated with incident AF (hazard ratio comparing top quartile to other 3 quartiles of homeostatic model assessment index 1.18, 95% confidence interval 0.84 to 1.65, p = 0.34). In a community-based cohort with <= 10 years of follow-up, no significant association was observed between insulin resistance and incident AF. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:87-90)
C1 [Fontes, Joao D.; Lyass, Asya; Massaro, Joseph M.; Rienstra, Michiel; Dallmeier, Dhayana; Schnabel, Renate B.; Wang, Thomas J.; Vasan, Ramachandran S.; Magnani, Jared W.; Levy, Daniel; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Fontes, Joao D.; Lyass, Asya; Massaro, Joseph M.; Rienstra, Michiel; Dallmeier, Dhayana; Schnabel, Renate B.; Wang, Thomas J.; Vasan, Ramachandran S.; Magnani, Jared W.; Levy, Daniel; Fox, Caroline S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Fontes, Joao D.; Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Lyass, Asya; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Rienstra, Michiel; Wang, Thomas J.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rienstra, Michiel] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands.
[Dallmeier, Dhayana] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, 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.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Benjamin, EJ (reprint author), NHLBI, Framingham, MA USA.
EM emelia@bu.edu
RI Schnabel, Renate/F-6527-2014;
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336;
Rienstra, Michiel/0000-0002-2581-070X
FU National Institutes of Health/National Heart, Lung, Blood Institute
(Bethesda, Maryland) [N01-HC-25195, 6R01-NS17950]; Boston University's
Framingham Heart Study (Framingham, Massachusetts [RO1AG028321,
1RC1HL101056, 1R01HL102214, 1R01HL092577, R01HL104156, R21DA027021,
K24HL105780]; National Institutes of Health (Bethesda, Maryland)
[1RO1HL71039]; Deutsche Forschungsgemeinschaft (German Research
Foundation) (Bonn, Germany) [SCHN 1149/1-1]; American Heart Association
[09FTF2190028]; Netherlands Organization for Scientific Research (Den
Haag, The Netherlands) [825.09.020]; Evans Center for Interdisciplinary
Biomedical Research ARC on Atrial Fibrillation Initiative at Boston
University (Boston, Massachusetts)
FX This study was supported by grants N01-HC-25195 and 6R01-NS17950 from
the National Institutes of Health/National Heart, Lung, Blood Institute
(Bethesda, Maryland) and Boston University's Framingham Heart Study
(Framingham, Massachusetts); grants RO1AG028321, 1RC1HL101056; and
1R01HL102214 (to E. J. Benjamin), 1R01HL092577 (to E. J. Benjamin and
P.T. Ellinor), R01HL104156, R21DA027021, and K24HL105780 (to P. T.
Ellinor), and 1RO1HL71039 (R. S. Vasan) from the National Institutes of
Health (Bethesda, Maryland); Deutsche Forschungsgemeinschaft (German
Research Foundation) (Bonn, Germany) Research Fellowship SCHN 1149/1-1
(to R. B. Schnabel); American Heart Association grant 09FTF2190028 (to
J.W. Magnani); and Rubicon grant 825.09.020 (to M. Rienstra) from The
Netherlands Organization for Scientific Research (Den Haag, The
Netherlands). This work was also partially supported by the Evans Center
for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation
Initiative at Boston University (Boston, Massachusetts) (available from:
http://www.bumc.bu.edu/evanscenteribr/thearcs/the-arcs/atrial-fibrillati
on-initiative-af-arc/).
NR 19
TC 14
Z9 14
U1 0
U2 2
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 JAN 1
PY 2012
VL 109
IS 1
BP 87
EP 90
DI 10.1016/j.amjcard.2011.08.008
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 873RJ
UT WOS:000298900400015
PM 21996140
ER
PT J
AU Ashida, S
Wilkinson, AV
Koehly, LM
AF Ashida, Sato
Wilkinson, Anna V.
Koehly, Laura M.
TI Social Influence and Motivation to Change Health Behaviors Among
Mexican-Origin Adults: Implications for Diet and Physical Activity
SO AMERICAN JOURNAL OF HEALTH PROMOTION
LA English
DT Article
DE Social Influence; Behavioral Motivation; Family Health History;
Mexican-American; Prevention Research
AB Purpose. To evaluate whether influence from social network members is associated with motivation to change dietary and physical activity behaviors.
Design. Baseline assessment followed by mailing of family health history based personalized messages (2 weeks) and follow-up assessment (3 months).
Setting. Families from an ongoing population-based cohort in Houston, Texas.
Subjects. 475 adults from 161 Mexican-origin families. Out of 347 households contacted, 162 (47%) participated.
Measures. Family health history, social networks, and motivation to change behaviors.
Analysis. Two-level logistic regression modeling.
Results. Having at least one network member who encourages one to eat more fruits and vegetables (p = .010) and to engage in regular physical activity (p = .046) was associated with motivation to change the relevant behavior. About 40% of the participants did not have encouragers for these behaviors.
Conclusions. Identification of new encouragers within networks and targeting natural encouragers (e.g., children, spouses) may increase the efficacy of interventions to motivate behavioral changes among Mexican-origin adults. (Am J Health Promot 2012;26131:176-179.)
C1 [Ashida, Sato] Univ Memphis, Div Social & Behav Sci, Sch Publ Hlth, Memphis, TN 38152 USA.
[Ashida, Sato; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Wilkinson, Anna V.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Ashida, S (reprint author), Univ Memphis, Div Social & Behav Sci, Sch Publ Hlth, Memphis, TN 38152 USA.
EM sashida@memphis.edu
FU Intramural NIH HHS [ZIA HG200335-05]; NCI NIH HHS [CA126988]; NHGRI NIH
HHS [Z01HG200335]
NR 10
TC 15
Z9 15
U1 1
U2 23
PU AMER JOURNAL HEALTH PROMOTION INC
PI TROY
PA PO BOX 1254, TROY, MI 48099-1254 USA
SN 0890-1171
J9 AM J HEALTH PROMOT
JI Am. J. Health Promot.
PD JAN-FEB
PY 2012
VL 26
IS 3
BP 176
EP 179
DI 10.4278/ajhp.100107-QUAN-2
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 880ZE
UT WOS:000299448300008
PM 22208416
ER
PT J
AU Nestadt, G
Wang, Y
Grados, MA
Riddle, MA
Greenberg, BD
Knowles, JA
Fyer, AJ
McCracken, JT
Rauch, SL
Murphy, DL
Rasmussen, SA
Cullen, B
Piacentini, J
Geller, D
Pauls, D
Bienvenu, OJ
Chen, Y
Liang, KY
Goes, FS
Maher, B
Pulver, AE
Shugart, YY
Valle, D
Samuels, JF
Chang, YC
AF Nestadt, G.
Wang, Y.
Grados, M. A.
Riddle, M. A.
Greenberg, B. D.
Knowles, J. A.
Fyer, A. J.
McCracken, J. T.
Rauch, S. L.
Murphy, D. L.
Rasmussen, S. A.
Cullen, B.
Piacentini, J.
Geller, D.
Pauls, D.
Bienvenu, O. J.
Chen, Y.
Liang, K. Y.
Goes, F. S.
Maher, B.
Pulver, A. E.
Shugart, Y. Y.
Valle, D.
Samuels, J. F.
Chang, Y. C.
TI Homeobox genes in obsessive-compulsive disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE OCD; PBX1; MEIS2; LMX1A; NANOG; genetic association
ID OCD COLLABORATIVE GENETICS; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTORS;
POLARIZING REGION; SELF-RENEWAL; MUTANT MICE; DNA-BINDING; PBX MARKS;
FAMILY; EXPRESSION
AB Background: Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis. Methods: In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4 kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families. Results: Three SNPs are most strongly associated with OCD: rs11854486 (P=0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR)=11.1 homozygous and 1.6 heterozygous) and rs4625687 [P=0.00007 (after adjustment=0.06); GRR=2.4] on 15q; and rs4387163 (P=0.0002 (after adjustment=0.08); GRR=1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150 kb between PBX1 and LMX1A. Conclusions: All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD. (C) 2011 Wiley Periodicals, Inc.
C1 [Nestadt, G.; Wang, Y.; Grados, M. A.; Riddle, M. A.; Cullen, B.; Bienvenu, O. J.; Goes, F. S.; Pulver, A. E.; Samuels, J. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Knowles, J. A.; Rasmussen, S. A.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA.
[Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, Manhattan, KS USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
[Rauch, S. L.; Geller, D.; Pauls, D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Rauch, S. L.; Geller, D.; Pauls, D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, S. L.; Geller, D.; Pauls, D.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA.
[Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Y.; Liang, K. Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Maher, B.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Shugart, Y. Y.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Shugart, Y. Y.] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
[Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Chang, Y. C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA.
EM gnestadt@jhmi.edu
RI Maher, Brion/F-9185-2010;
OI Samuels, Jack/0000-0002-6715-7905
FU National Institute of Health [R01-MH-50214, NIH/NCRR/OPD-GCRC RR00052]
FX Grant sponsor: National Institute of Health; Grant numbers:
R01-MH-50214, NIH/NCRR/OPD-GCRC RR00052.
NR 62
TC 10
Z9 10
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JAN
PY 2012
VL 159B
IS 1
BP 53
EP 60
DI 10.1002/ajmg.b.32001
PG 8
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 868QC
UT WOS:000298536800008
PM 22095678
ER
PT J
AU Judy, JT
Seifuddin, F
Mahon, PB
Huo, YQ
Goes, FS
Jancic, D
Schweizer, B
Mondimore, FM
MacKinnon, DF
DePaulo, JR
Gershon, ES
McMahon, FJ
Cutler, DJ
Zandi, PP
Potash, JB
Willour, VL
AF Judy, Jennifer T.
Seifuddin, Fayaz
Mahon, Pamela B.
Huo, Yuqing
Goes, Fernando S.
Jancic, Dubravka
Schweizer, Barbara
Mondimore, Francis M.
MacKinnon, Dean F.
DePaulo, J. Raymond, Jr.
Gershon, Elliot S.
McMahon, Francis J.
Cutler, David J.
Zandi, Peter P.
Potash, James B.
Willour, Virginia L.
TI Association study of serotonin pathway genes in attempted suicide
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE suicidal behavior; bipolar disorder; major depression
ID RANDOMIZED CONTROLLED-TRIALS; GENOME-WIDE ASSOCIATION; DIAGNOSTIC
INTERVIEW; REUPTAKE INHIBITORS; GENETICS; BEHAVIOR; DEPRESSION;
DISORDERS; LINKAGE; SAMPLE
AB Epidemiological studies, such as family, twin, and adoption studies, demonstrate the presence of a heritable component to both attempted and completed suicide. Some of this heritability is accounted for by the presence of comorbid psychiatric disorders, but the evidence also indicates that a portion of this heritability is specific to suicidality. The serotonergic system has been studied extensively in this phenotype, but findings have been inconsistent, possibly due to the presence of multiple susceptibility variants and/or genegene interactions. In this study, we genotyped 174 tag and coding single nucleotide polymorphisms (SNPs) from 17 genes within the serotonin pathway on 516 subjects with a major mood disorder and a history of a suicide attempt (cases) and 515 healthy controls, with the goal of capturing the common genetic variation across each of these candidate genes. We tested the 174 markers in single-SNP, haplotype, gene-based, and epistasis analyses. While these association analyses identified multiple marginally significant SNPs, haplotypes, genes, and interactions, none of them survived correction for multiple testing. Additional studies, including assessment in larger sample sets and deep resequencing to identify rare causal variants, may be required to fully understand the role that the serotonin pathway plays in suicidal behavior. (C) 2011 Wiley Periodicals, Inc.
C1 [Potash, James B.; Willour, Virginia L.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA.
[Judy, Jennifer T.; Seifuddin, Fayaz; Mahon, Pamela B.; Huo, Yuqing; Goes, Fernando S.; Jancic, Dubravka; Schweizer, Barbara; Mondimore, Francis M.; MacKinnon, Dean F.; DePaulo, J. Raymond, Jr.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Cutler, David J.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
RP Willour, VL (reprint author), Univ Iowa, Carver Coll Med, Dept Psychiat, 500 Newton Rd,Med Labs B002J, Iowa City, IA 52242 USA.
EM virginia-willour@uiowa.edu
OI McMahon, Francis/0000-0002-9469-305X
FU National Institute of Mental Health [MH079240]; American Foundation for
Suicide Prevention; Margaret Price Investigatorships
FX Grant sponsor: National Institute of Mental Health; Grant number:
MH079240; Grant sponsor: American Foundation for Suicide Prevention.;
This work was supported by grants from the National Institute of Mental
Health (MH079240 to V. L. W.) and the American Foundation for Suicide
Prevention (V.L.W.). Dr. Willour and Dr. Potash were also supported by
Margaret Price Investigatorships. Some DNA samples were prepared and
distributed by Rutgers University under a contract from the NIMH. We are
grateful to the many interviewers and diagnosticians who contributed to
this project, and to the families who devoted their time and effort to
the study. The Bipolar Disorder Phenome Group consists of Francis
McMahon, Jo Steele, Justin Pearl, Layla Kassem, Victor Lopez from the
Genetic Basis of Mood and Anxiety Disorders Unit, Mood and Anxiety
Program, National Institute of Mental Health, National Institutes of
Health, Bethesda, MD; James Potash, Dean MacKinnon, Erin Miller,
Jennifer Toolan from the Department of Psychiatry, Johns Hopkins School
of Medicine, Baltimore, MD; Peter Zandi from the Department of Mental
Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
Thomas Schulze from the Division of Genetic Epidemiology in Psychiatry,
Central Institute of Mental Health, Ruprecht-Karls-University of
Heidelberg, Mannheim, Germany; Evaristus Nwulia from the Department of
Psychiatry, Howard University Hospital, Washington, D.C.; Sylvia Simpson
from the Department of Psychiatry, University of Colorado at Denver,
Denver, CO. Acknowledgment for Bipolar Disorder Biomaterials and
Clinical Data: Data and biomaterials were collected in four projects
that participated in the National Institute of Mental Health (NIMH)
Bipolar Disorder Genetics Initiative. From 1991 to 1998, the Principal
Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, U01MH46282, John Nurnberger M.D., Ph.D., Marvin Miller
M.D., and Elizabeth Bowman M.D.; Washington University, St. Louis, MO,
U01 MH46280, Theodore Reich M.D., Allison Goate Ph.D., and John Rice
Ph.D.; Johns Hopkins University, Baltimore, MD U01 MH46274, J. Raymond
DePaulo Jr M.D., Sylvia Simpson M.D., MPH, and Colin Stine Ph.D.; NIMH
Intramural Research Program, Clinical Neurogenetics Branch, Bethesda,
MD, Elliot Gershon M.D., Diane Kazuba B.A., and Elizabeth Maxwell M.S.W.
Data and biomaterials were collected as part of 10 projects that
participated in the National Institute of Mental Health (NIMH) Bipolar
Disorder Genetics Initiative. From 1999 to 2003, the Principal
Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, R01 MH59545, John Nurnberger M.D., Ph.D., Marvin J.
Miller M.D., Elizabeth S. Bowman M.D., N. Leela Rau M.D., P. Ryan Moe
M.D., Nalini Samavedy M.D., Rif El-Mallakh M.D. (at University of
Louisville), Husseini Manji M.D. (at Wayne State University), Debra A.
Glitz M.D. (at Wayne State University), Eric T. Meyer M.S., Carrie
Smiley R.N., Tatiana Foroud Ph.D., Leah Flury M.S., Danielle M. Dick
Ph.D., Howard Edenberg Ph.D.; Washington University, St. Louis, MO, R01
MH059534, John Rice Ph.D., Theodore Reich M.D., Allison Goate Ph.D.,
Laura Bierut M. D.; Johns Hopkins University, Baltimore, MD, R01
MH59533, Melvin McInnis M.D., J. Raymond DePauloJr M.D., Dean F.
MacKinnon M.D., Francis M. Mondimore M.D., James B. Potash M.D., Peter
P. Zandi Ph.D., Dimitrios Avramopoulos, and Jennifer Payne; University
of Pennsylvania, PA, R01 MH59553, Wade Berrettini M.D., Ph.D.;
University of California at Irvine, CA, R01 MH60068, William Byerley
M.D., and Mark Vawter M.D.; University of Iowa, IA, R01 MH059548,
William Coryell M.D., and Raymond Crowe M.D.; ; University of Chicago,
IL, R01 MH59535,Elliot Gershon, M.D., Judith Badner Ph. D., Francis
McMahon M.D., Chunyu Liu Ph.D., Alan Sanders M.D., Maria Caserta, Steven
Dinwiddie M.D., Tu Nguyen, Donna Harakal; University of California at
San Diego, CA, R01 MH59567, John Kelsoe M.D., Rebecca McKinney B. A.;
Rush University, IL, R01 MH059556, William Scheftner M.D., Howard M.
Kravitz D.O., M.P.H., Diana Marta B.S., Annette Vaughn-Brown MSN, RN,
and Laurie Bederow MA; NIMH Intramural Research Program, Bethesda, MD,
1Z01MH002810-01, Francis J. McMahon M.D., Layla Kassem PsyD, Sevilla
Detera-Wadleigh Ph.D., Lisa Austin Ph.D, Dennis L. Murphy M.D.
Acknowledgment for Depression Sample Biomaterials and Clinical Data:
Data and biomaterials were collected in six projects that participated
in the National Institute of Mental Health (NIMH) Genetics of Recurrent
Early-Onset Depression (GenRED) Project. From 1999 to 2003, the
Principal Investigators and Co-Investigators were: New York State
Psychiatric Institute, New York, NY, R01 MH060912, Myrna M. Weissman Ph.
D. and James K. Knowles M.D., Ph. D.; University of Pittsburgh,
Pittsburgh, PA, R01 MH060866, George S. Zubenko M.D., Ph.D. and Wendy N.
Zubenko Ed. D., R.N., C.S.; Johns Hopkins University, Baltimore, R01
MH059552, J. Raymond DePaulo M.D., Melvin G. McInnis M.D., and Dean
MacKinnon M. D.; University of Pennsylvania, Philadelphia, PA, RO1
MH61686, Douglas F. Levinson M.D. (GenRED coordinator), Madeleine M.
Gladis Ph.D., Kathleen Murphy-Eberenz Ph.D., and Peter Holmans Ph.D.
(University of Wales College of Medicine); University of Iowa, Iowa
City, IA, R01 MH059542, Raymond R. Crowe M.D. and William H. Coryell
M.D.; Rush University Medical Center, Chicago, IL, R01 MH059541-05,
William A. Scheftner M.D., Rush-Presbyterian. Acknowledgment for Control
Sample Biomaterials and Clinical Data: Control subjects from the
National Institute of Mental Health Schizophrenia Genetics Initiative
(NIMH-GI), data and biomaterials are being collected by the "Molecular
Genetics of Schizophrenia II'' (MGS-2) Collaboration. The Investigators
and Co-Investigators are: ENH/Northwestern University, Evanston, IL,
MH059571, Pablo V. Gejman M. D. (Collaboration Coordinator; P. I.), Alan
R. Sanders M. D.; Emory University School of Medicine, Atlanta, GA,
MH59587, Farooq Amin M. D. (P. I.); Louisiana State University Health
Sciences Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN,
BC, MSN (P.I.); University of California-Irvine, Irvine, CA, MH60870,
William Byerley M.D. (P.I.); Washington University, St. Louis, MO, U01,
MH060879, C. Robert Cloninger M.D. (P.I.); University of Iowa, IA,
MH59566, Raymond Crowe M.D. (P.I.), Donald Black M.D.; University of
Colorado, Denver, CO, MH059565, Robert Freedman M.D. (P.I.); University
of Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson M.D.
(P.I.); University of Queensland, Queensland, Australia, MH059588, Bryan
Mowry M.D. (P.I.); Mt. Sinai School of Medicine, New York, NY, MH59586,
Jeremy Silverman Ph.D. (P.I.). In addition, cord blood samples were
collected by V L Nimgaonkar's Group at the University of Pittsburgh, as
part of a Multi-Institutional Collaborative Research Project with J.
Smoller M.D.D. Sc. and P. Sklar M.D., Ph.D. (Massachusetts General
Hospital, grant MH 63420).
NR 32
TC 6
Z9 6
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JAN
PY 2012
VL 159B
IS 1
BP 112
EP 119
DI 10.1002/ajmg.b.32008
PG 8
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 868QC
UT WOS:000298536800015
PM 22170779
ER
PT J
AU Goldman, SM
Kamel, F
Ross, GW
Jewell, SA
Bhudhikanok, GS
Umbach, D
Marras, C
Hauser, RA
Jankovic, J
Factor, SA
Bressman, S
Lyons, KE
Meng, C
Korell, M
Roucoux, DF
Hoppin, JA
Sandler, DP
Langston, JW
Tanner, CM
AF Goldman, Samuel M.
Kamel, Freya
Ross, G. Webster
Jewell, Sarah A.
Bhudhikanok, Grace S.
Umbach, David
Marras, Connie
Hauser, Robert A.
Jankovic, Joseph
Factor, Stewart A.
Bressman, Susan
Lyons, Kelly E.
Meng, Cheryl
Korell, Monica
Roucoux, Diana F.
Hoppin, Jane A.
Sandler, Dale P.
Langston, J. William
Tanner, Caroline M.
TI Head injury, alpha-synuclein Rep1, and Parkinson's disease
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID TRAUMATIC BRAIN-INJURY; ENVIRONMENTAL RISK-FACTORS; CELL-DEATH;
INFLAMMATORY RESPONSE; AMYLOID-BETA; RAT MODEL; EXPRESSION; POPULATION;
ACCUMULATION; PATHOGENESIS
AB Objective: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding a-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk. Methods: Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury. Results: Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95-2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9-1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5-19; SEARCH OR, 2.3; 95% CI, 0.6-9.2; pooled OR, 3.5; 95% CI 1.4-9.2, p-interaction 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p 0.03). Interpretation: While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/ or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential. ANN NEUROL 2012; 71: 40-48
C1 [Goldman, Samuel M.; Jewell, Sarah A.; Bhudhikanok, Grace S.; Meng, Cheryl; Korell, Monica; Roucoux, Diana F.; Langston, J. William; Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA 94085 USA.
[Kamel, Freya; Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Umbach, David] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Jewell, Sarah A.] German Ctr Neurodegenerat Dis, DZNE, Bonn, Germany.
[Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada.
[Hauser, Robert A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA.
[Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Bressman, Susan] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA.
[Lyons, Kelly E.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
RP Goldman, SM (reprint author), Parkinsons Inst, 675 Almanor Ave, Sunnyvale, CA 94085 USA.
EM sgoldman@thepi.org
RI Hauser, Robert/I-5372-2012; Goldman, Samuel/A-2225-2014;
OI Jewell, Sarah/0000-0002-9877-2599; Goldman, Samuel/0000-0002-3039-9927;
Sandler, Dale/0000-0002-6776-0018
FU NIH (National Institute of Environmental Health Sciences [NIEHS])
[Z01-ES044007, Z01-ES049030, R01-ES10803, U54 ES012077, NCI
Z01-CP010119]; Michael J. Fox Foundation
FX This research was supported in part by the Intramural Research Program
of the NIH (National Institute of Environmental Health Sciences [NIEHS]
Z01-ES044007, Z01-ES049030, R01-ES10803 (C. M. T.), U54 ES012077 (C. M.
T., J.W.L.); NCI Z01-CP010119); Michael J. Fox Foundation (C. M. T., J.
W. L.); Parkinson's Unity Walk; James and Sharron Clark. SEARCH was
supported by an unrestricted grant from a group of current and former
manufacturers of welding consumables awarded to The Parkinson's
Institute.
NR 68
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Z9 34
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD JAN
PY 2012
VL 71
IS 1
BP 40
EP 48
DI 10.1002/ana.22499
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 880MW
UT WOS:000299412200008
PM 22275250
ER
PT J
AU Bielekova, B
McFarland, H
AF Bielekova, Bibiana
McFarland, Henry
TI Comment on "Interleukin-2/Interleukin-2 Antibody Therapy Induces Target
Organ Natural Killer Cells That Inhibit Central Nervous System
Inflammation"
SO ANNALS OF NEUROLOGY
LA English
DT Letter
C1 [Bielekova, Bibiana; McFarland, Henry] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD JAN
PY 2012
VL 71
IS 1
BP 148
EP 149
DI 10.1002/ana.22547
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 880MW
UT WOS:000299412200022
PM 22275261
ER
PT J
AU Friesen, MC
Coble, JB
Lu, W
Shu, XO
Ji, BT
Xue, SZ
Portengen, L
Chow, WH
Gao, YT
Yang, G
Rothman, N
Vermeulen, R
AF Friesen, Melissa C.
Coble, Joseph B.
Lu, Wei
Shu, Xiao-Ou
Ji, Bu-Tian
Xue, Shouzheng
Portengen, Lutzen
Chow, Wong-Ho
Gao, Yu-Tang
Yang, Gong
Rothman, Nathaniel
Vermeulen, Roel
TI Combining a Job-Exposure Matrix with Exposure Measurements to Assess
Occupational Exposure to Benzene in a Population Cohort in Shanghai,
China
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE benzene; job-exposure matrix; mixed-effects models; retrospective
exposure assessment
ID LONG-TERM TRENDS; RUBBER MANUFACTURING-INDUSTRY; RETROSPECTIVE EXPOSURE;
COMPREHENSIVE EVALUATION; WOOD DUST; INHALABLE PARTICULATE; HISTORICAL
EXPOSURES; INHALATION EXPOSURE; US INDUSTRIES; RISK
AB Generic job-exposure matrices (JEMs) are often used in population-based epidemiologic studies to assess occupational risk factors when only the job and industry information of each subject is available. JEM ratings are often based on professional judgment, are usually ordinal or semi-quantitative, and often do not account for changes in exposure over time. We present an empirical Bayesian framework that combines ordinal subjective JEM ratings with benzene measurements. Our aim was to better discriminate between job, industry, and time differences in exposure levels compared to using a JEM alone.
We combined 63 221 short-term area air measurements of benzene exposure (1954-2000) collected during routine health and safety inspections in Shanghai, China, with independently developed JEM intensity ratings for each job and industry using a mixed-effects model. The fixed-effects terms included the JEM intensity ratings for job and industry (both ordinal, 0-3) and a time trend that we incorporated as a b-spline. The random-effects terms included job (n = 33) and industry nested within job (n = 399). We predicted the benzene concentration in two ways: (i) a calibrated JEM estimate was calculated using the fixed-effects model parameters for calendar year and JEM intensity ratings; (ii) a job-/industry-specific estimate was calculated using the fixed-effects model parameters and the best linear unbiased predictors from the random effects for job and industry using an empirical Bayes estimation procedure. Finally, we applied the predicted benzene exposures to a prospective population-based cohort of women in Shanghai, China (n = 74 942).
Exposure levels were 13 times higher in 1965 than in 2000 and declined at a rate that varied from 4 to 15% per year from 1965 to 1985, followed by a small peak in the mid-1990s. The job-/industry-specific estimates had greater differences between exposure levels than the calibrated JEM estimates (97.5th percentile/2.5th percentile exposure level, (BG)R(95B): 20.4 versus 3.0, respectively). The calibrated JEM and job-/industry-specific estimates were moderately correlated in any given year (Pearson correlation, r(p) = 0.58). We classified only those jobs and industries with a job or industry JEM exposure probability rating of 3 (> 50% of workers exposed) as exposed. As a result, 14.8% of the subjects and 8.7% of the employed person-years in the study population were classified as benzene exposed. The cumulative exposure metrics based on the calibrated JEM and job-/industry-specific estimates were highly correlated (r(p) = 0.88).
We provide a useful framework for combining quantitative exposure data with expert-based exposure ratings in population-based studies that maximized the information from both sources. Our framework calibrated the ratings to a concentration scale between ratings and across time and provided a mechanism to estimate exposure when a job/industry group reported by a subject was not represented in the exposure database. It also allowed the job/industry groups' exposure levels to deviate from the pooled average for their respective JEM intensity ratings.
C1 [Friesen, Melissa C.; Coble, Joseph B.; Ji, Bu-Tian; Xue, Shouzheng; Chow, Wong-Ho; Rothman, Nathaniel; Vermeulen, Roel] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control, Shanghai, Peoples R China.
[Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Div Epidemiol, Dept Med, Vanderbilt Epidemiol Ctr,Sch Med, Nashville, TN 37203 USA.
[Portengen, Lutzen; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, Utrecht, Netherlands.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Friesen, MC (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011; Friesen, Melissa/A-5362-2009
OI Vermeulen, Roel/0000-0003-4082-8163;
FU US National Institutes of Health [R37 CA70867]; National Institutes of
Health [N02 CP1101066]; Shanghai Women's Health Study; Shanghai CDC
FX US National Institutes of Health (R37 CA70867); Intramural Research
Program of the National Institutes of Health (contract N02 CP1101066).;
The authors thank the research staff of the Shanghai Women's Health
Study and the Shanghai CDC for their support and contributions to the
study.
NR 57
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Z9 23
U1 0
U2 13
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 JAN
PY 2012
VL 56
IS 1
BP 80
EP 91
DI 10.1093/annhyg/mer080
PG 12
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA 879RN
UT WOS:000299349800010
PM 21976309
ER
PT J
AU Yu, BB
AF Yu, Binbing
TI A minimum version of log-rank test for testing the existence of cancer
cure using relative survival data
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE Log-rank test; Relative survival; SEER Program; Test of noninferiority
ID EFFICIENCY ROBUST-TESTS; LOGRANK TEST; MODELS
AB Cancer survival is one of the most important measures to evaluate the effectiveness of treatment and early diagnosis. The ultimate goal of cancer research and patient care is the cure of cancer. As cancer treatments progress, cure becomes a reality for many cancers if patients are diagnosed early and get effective treatment. If a cure does exist for a certain type of cancer, it is useful to estimate the time of cure. For cancers that impose excess risk of mortality, it is informative to understand the difference in survival between cancer patients and the general cancer-free population. In population-based cancer survival studies, relative survival is the standard measure of excess mortality due to cancer. Cure is achieved when the survival of cancer patients is equivalent to that of the general population. This definition of cure is usually called the statistical cure, which is an important measure of burden due to cancer. In this paper, a minimum version of the log-rank test is proposed to test the equivalence of cancer patients' survival using the relative survival data. Performance of the proposed test is evaluated by simulation. Relative survival data from population-based cancer registries in SEER Program are used to examine patients' survival after diagnosis for various major cancer sites.
C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM yubi@mail.nih.gov
FU National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging. The author thank the Associate
Editor and two anonymous reviewers for their insightful comments and to
thank Ms. Caroline Phillips for her conscientious and careful editorial
help.
NR 20
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
EI 1521-4036
J9 BIOMETRICAL J
JI Biom. J.
PD JAN
PY 2012
VL 54
IS 1
SI SI
BP 45
EP 60
DI 10.1002/bimj.201100069
PG 16
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 872VY
UT WOS:000298839300003
PM 22213092
ER
PT J
AU Ankerst, DP
Koniarski, T
Liang, YY
Leach, RJ
Feng, ZD
Sanda, MG
Partin, AW
Chan, DW
Kagan, J
Sokoll, L
Wei, JT
Thompson, IM
AF Ankerst, Donna P.
Koniarski, Tim
Liang, Yuanyuan
Leach, Robin J.
Feng, Ziding
Sanda, Martin G.
Partin, Alan W.
Chan, Daniel W.
Kagan, Jacob
Sokoll, Lori
Wei, John T.
Thompson, Ian M.
TI Updating risk prediction tools: A case study in prostate cancer
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE Calibration; Discrimination; Net benefit; Prostate cancer prevention
trial; Risk prediction; Validation
ID DECISION CURVE ANALYSIS; OPERATING CHARACTERISTICS; PREVENTION TRIAL;
BREAST-CANCER; ROC CURVE; MODELS; MARKER; RECLASSIFICATION; STATISTICS;
CALCULATOR
AB Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external casecontrol study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network.
C1 [Ankerst, Donna P.] Tech Univ Muenchen, Dept Math, Unit M4, D-85748 Garching, Germany.
[Ankerst, Donna P.; Liang, Yuanyuan; Leach, Robin J.; Thompson, Ian M.] UTHSCSA, Dept Urol, San Antonio, TX 78229 USA.
[Ankerst, Donna P.; Liang, Yuanyuan] UTHSCSA, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Koniarski, Tim] Univ Regensburg, Int Real Estate Business Sch, D-93040 Regensburg, Germany.
[Feng, Ziding] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA.
[Sanda, Martin G.] Harvard Univ, Sch Med, Dept Urol, Boston, MA 02215 USA.
[Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Prostate Ctr, Boston, MA 02215 USA.
[Partin, Alan W.; Chan, Daniel W.; Sokoll, Lori] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Partin, Alan W.; Chan, Daniel W.; Sokoll, Lori] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA.
[Kagan, Jacob] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD USA.
[Wei, John T.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
RP Ankerst, DP (reprint author), Tech Univ Muenchen, Dept Math, Unit M4, Boltzmannstr 3, D-85748 Garching, Germany.
EM ankerst@ma.tum.de
RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei,
John/E-8967-2012
FU National Institutes of Health [CA086402, CA054174, CA86323,
UO1CA113913]; EDRN [CA115102]; National Cancer Institute Cancer Center
[CTRC: 5P30 CA0541474-18]
FX This research was supported by National Institutes of Health grants
CA086402, CA054174, CA86323, UO1CA113913, EDRN grant CA115102, and a
National Cancer Institute Cancer Center support grant to the UTHSCSA
CTRC: 5P30 CA0541474-18. The authors thank the SABOR and EDRN
participants.
NR 33
TC 17
Z9 17
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD JAN
PY 2012
VL 54
IS 1
SI SI
BP 127
EP 142
DI 10.1002/bimj.201100062
PG 16
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 872VY
UT WOS:000298839300008
PM 22095849
ER
PT J
AU Sakurai, A
Doci, C
Gutkind, JS
AF Sakurai, Atsuko
Doci, Colleen
Gutkind, J. Silvio
TI Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer
SO CELL RESEARCH
LA English
DT Review
DE semaphorin; signaling; angiogenesis; lymphangiogenesis; cancer
ID ENDOTHELIAL-GROWTH-FACTOR; LYMPH-NODE METASTASIS; NUCLEOTIDE EXCHANGE
FACTORS; TUMOR-INDUCED ANGIOGENESIS; GTPASE-ACTIVATING PROTEIN;
FACTOR-C; FACTOR RECEPTOR-3; BREAST-CANCER; SUPPRESSOR GENE; CELL
MOTILITY
AB Angiogenesis, the formation of new blood vessels from preexisting vasculature, is essential for many physiological processes, and aberrant angiogenesis contributes to some of the most prevalent human diseases, including cancer. Angiogenesis is controlled by delicate balance between pro- and anti-angiogenic signals. While pro- angiogenic signaling has been extensively investigated, how developmentally regulated, naturally occurring anti-angiogenic molecules prevent the excessive growth of vascular and lymphatic vessels is still poorly understood. In this review, we summarize the current knowledge on how semaphorins and their receptors, plexins and neuropilins, control normal and pathological angiogenesis, with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in vascular and lymphatic endothelial cells. This emerging body of information may afford the opportunity to develop novel anti-angiogenic therapeutic strategies.
C1 [Sakurai, Atsuko; Doci, Colleen; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
RI Gutkind, J. Silvio/A-1053-2009
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research.
NR 105
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Z9 56
U1 0
U2 9
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD JAN
PY 2012
VL 22
IS 1
BP 23
EP 32
DI 10.1038/cr.2011.198
PG 10
WC Cell Biology
SC Cell Biology
GA 879EQ
UT WOS:000299312900007
PM 22157652
ER
PT J
AU Ryan, PM
Bourdi, M
Korrapati, MC
Proctor, WR
Vasquez, RA
Yee, SB
Quinn, TD
Chakraborty, M
Pohl, LR
AF Ryan, Pauline M.
Bourdi, Mohammed
Korrapati, Midhun C.
Proctor, William R.
Vasquez, Ronald A.
Yee, Steven B.
Quinn, Timothy D.
Chakraborty, Mala
Pohl, Lance R.
TI Endogenous Interleukin-4 Regulates Glutathione Synthesis Following
Acetaminophen-Induced Liver Injury in Mice
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; INDUCED HEPATOTOXICITY; MOUSE-LIVER;
IMMUNE-RESPONSES; COVALENT BINDING; OXIDATIVE STRESS; GENE-EXPRESSION;
CRUCIAL ROLE; CD-1 MICE; T-CELLS
AB In a recent study, we reported that interleukin (IL)-4 had a protective role against acetaminophen (APAP)-induced liver injury (AILI), although the mechanism of protection was unclear. Here, we carried out more detailed investigations and have shown that one way IL-4 may control the severity of AILI is by regulating glutathione (GSH) synthesis. In the present studies, the protective role of IL-4 in AILI was established definitively by showing that C57BL/6J mice made deficient in IL-4 genetically (IL-4(-/-)) or by depletion with an antibody, were more susceptible to ALLI than mice not depleted of IL-4. The increased susceptibility of IL-4(-/-) mice was not due to elevated levels of hepatic APAP-protein adducts but was associated with a prolonged reduction in hepatic GSH that was attributed to decreased gene expression of gamma-glutamylcysteine ligase (gamma-GCL). Moreover, administration of recombinant IL-4 to IL-4(-/-) mice postacetaminophen treatment diminished the severity of liver injury and increased gamma-GCL and GSH levels. We also report that the prolonged reduction of GSH in APAP-treated IL-4(-/-) mice appeared to contribute toward increased liver injury by causing a sustained activation of c-Jun-N-terminal kinase (JNK) since levels of phosphorylated JNK remained significantly higher in the IL-4(-/-) mice up to 24 h after APAP treatment. Overall, these results show for the first time that IL-4 has a role in regulating the synthesis of GSH in the liver under conditions of cellular stress. This mechanism appears to be responsible at least in part for the protective role of IL-4 against AILI in mice and may have a similar role not only in AILI in humans but also in pathologies of the liver caused by other drugs and etiologies.
C1 [Ryan, Pauline M.; Bourdi, Mohammed; Korrapati, Midhun C.; Proctor, William R.; Vasquez, Ronald A.; Yee, Steven B.; Quinn, Timothy D.; Chakraborty, Mala; Pohl, Lance R.] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, Ctr Immunol,NIH, Bethesda, MD 20892 USA.
RP Pohl, LR (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, Ctr Immunol,NIH, 9000 Rockville Pike,Bldg 10,Room 8N110, Bethesda, MD 20892 USA.
EM pohll@nih.gov
FU National Institutes of Health; National Heart Lung and Blood Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and the National Heart Lung and Blood
Institute.
NR 62
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Z9 19
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD JAN
PY 2012
VL 25
IS 1
BP 83
EP 93
DI 10.1021/tx2003992
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 875KL
UT WOS:000299028700010
PM 22107450
ER
PT J
AU Bjarnason, T
Bendtsen, P
Arnarsson, AM
Borup, I
Iannotti, RJ
Lofstedt, P
Haapasalo, I
Niclasen, B
AF Bjarnason, Thoroddur
Bendtsen, Pernille
Arnarsson, Arsaell M.
Borup, Ina
Iannotti, Ronald J.
Lofstedt, Petra
Haapasalo, Ilona
Niclasen, Birgit
TI Life Satisfaction Among Children in Different Family Structures: A
Comparative Study of 36 Western Societies
SO CHILDREN & SOCIETY
LA English
DT Article
DE health and well-being; international childhoods; welfare
ID SCHOOL-AGED CHILDREN; NONRESIDENT FATHERS; EMOTIONAL DISTRESS; DIVORCE;
BEHAVIORS; ARRANGEMENTS; METAANALYSIS; DELINQUENCY; ADOLESCENTS;
ADJUSTMENT
AB This paper examines differences in life satisfaction among children in different family structures in 36 western, industrialised countries (n = 184 496). Children living with both biological parents reported higher levels of life satisfaction than children living with a single parent or parentstep-parent. Children in joint physical custody reported significantly higher levels of life satisfaction than their counterparts in other types of non-intact families. Controlling perceived family affluence, the difference between joint physical custody families and single mother or motherstepfather families became non-significant. Difficulties in communicating with parents were strongly associated with less life satisfaction but did not mediate the relation between family structure and life satisfaction. Children in the Nordic countries characterised by strong welfare systems reported significantly higher levels of life satisfaction in all living arrangements except in single father households. Differences in economic inequality between countries moderated the association between certain family structures, perceived family affluence and life satisfaction.
C1 [Bjarnason, Thoroddur] Univ Akureyri, Dept Social Sci, IS-600 Akureyri, Iceland.
[Bendtsen, Pernille] Univ Copenhagen, Copenhagen, Denmark.
[Borup, Ina] Nord Sch Publ Hlth, Gothenburg, Sweden.
[Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Lofstedt, Petra] Karolinska Inst, Stockholm, Sweden.
[Haapasalo, Ilona] Univ Jyvaskyla, Jyvaskyla, Finland.
[Niclasen, Birgit] Greenland Inst Hlth Res, Nuuk, Greenland.
RP Bjarnason, T (reprint author), Univ Akureyri, Dept Social Sci, IS-600 Akureyri, Iceland.
EM thorodd@unak.is
OI Bendtsen, Pernille/0000-0003-4031-738X
NR 40
TC 14
Z9 14
U1 6
U2 56
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-0605
J9 CHILD SOC
JI Child. Soc.
PD JAN
PY 2012
VL 26
IS 1
BP 51
EP 62
DI 10.1111/j.1099-0860.2010.00324.x
PG 12
WC Social Work
SC Social Work
GA 867UM
UT WOS:000298480300006
ER
PT J
AU Roger, VL
O'Donnell, CJ
AF Roger, Veronique L.
O'Donnell, Christopher J.
TI Population Health, Outcomes Research, and Prevention Example of the
American Heart Association 2020 Goals
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Editorial Material
DE prevention; delivery of health care; outcomes assessment
ID CLINICAL-PRACTICE GUIDELINES; NEW-YORK-CITY; CARDIOVASCULAR-DISEASE;
CARE; BEHAVIOR; ERA
C1 [Roger, Veronique L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Roger, Veronique L.] Mayo Clin, Div Cardiovasc Dis, Dept Internal Med, Rochester, MN 55905 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBI Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Dept Internal Med, Boston, MA 02114 USA.
RP Roger, VL (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA.
EM roger.veronique@mayo.edu
FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [R01 HL059205-13, R01
HL072435, R01 HL072435-08, R01 HL59205, R01 HL059205, R01 HL72435]
NR 25
TC 5
Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JAN
PY 2012
VL 5
IS 1
BP 6
EP 8
DI 10.1161/CIRCOUTCOMES.111.964734
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 880ML
UT WOS:000299411100002
PM 22253367
ER
PT J
AU Pavkov, ME
Knowler, WC
Lemley, KV
Mason, CC
Myers, BD
Nelson, RG
AF Pavkov, Meda E.
Knowler, William C.
Lemley, Kevin V.
Mason, Clinton C.
Myers, Bryan D.
Nelson, Robert G.
TI Early Renal Function Decline in Type 2 Diabetes
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; KIDNEY-FUNCTION;
PIMA-INDIANS; MICROALBUMINURIA; PROGRESSION; GFR; INDIVIDUALS;
NEPHROPATHY; CREATININE
AB Background and objectives Early decline in GFR may reflect progressive kidney disease in type 1 diabetes, but its predictive value in type 2 diabetes is uncertain.
Design, setting, participants, & measurements In this longitudinal study, GFR was measured serially over approximately 4.0 years in 195 Pima Indians with type 2 diabetes. Renal function decline (RFD) was defined during this initial period by an average GFR loss >= 3.3%/yr, as defined previously in type 1 diabetes. Subsequently, participants were followed for up to 17.8 years to ESRD onset, death, or December 31, 2010, whichever came first.
Results RFD prevalence during the initial period was 32% in 68 participants with normal baseline albuminuria (albumin/creatinine ratio [ACR] <30 mg/g), 42% in 88 with microalbuminuria (ACR 30 to <300 mg/g), and 74% in 39 with macroalbuminuria (ACR >= 300 mg/g; P<0.001). The cumulative incidence of ESRD 10 years after the initial period was 41% in those with RFD and 15% in those without (P<0.001); 41 of the 49 ESRD cases (83.7%) occurred in participants who had or developed macroalbuminuria during the initial period. When adjusted for age, sex, diabetes duration, and hemoglobin A1c, the ESRD hazard rate was 4.78 times (95% confidence interval, 2.39-9.58) as high in those with RFD as in those without; further adjustment for albuminuria attenuated this association (hazard ratio, 1.79; 95% confidence interval, 0.82-3.91).
Conclusions In type 2 diabetes, loss of GFR often occurs before the onset of macroalbuminuria, but a decline predictive of ESRD is strongly dependent on progression to macroalbuminuria. Clin J Am Soc Nephrol 7: 78-84, 2012. doi: 10.2215/CJN.07610711
C1 [Pavkov, Meda E.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA.
[Knowler, William C.; Mason, Clinton C.; Nelson, Robert G.] NIDDK, NIH, Phoenix, AZ USA.
[Lemley, Kevin V.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90033 USA.
[Myers, Bryan D.] Stanford Univ, Sch Med, Div Nephrol, Stanford, CA 94305 USA.
RP Pavkov, ME (reprint author), Ctr Dis Control & Prevent, 4770 Buford Hwy NE,MS-K10, Atlanta, GA 30341 USA.
EM mpavkov@cdc.gov
RI Nelson, Robert/B-1470-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 23
TC 27
Z9 29
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JAN
PY 2012
VL 7
IS 1
BP 78
EP 84
DI 10.2215/CJN.07610711
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 877RD
UT WOS:000299198700014
PM 22076874
ER
PT J
AU Semba, RD
Fink, JC
Sun, K
Cappola, AR
Dalal, M
Crasto, C
Ferrucci, L
Fried, LP
AF Semba, Richard D.
Fink, Jeffrey C.
Sun, Kai
Cappola, Anne R.
Dalal, Mansi
Crasto, Candace
Ferrucci, Luigi
Fried, Linda P.
TI Serum Fibroblast Growth Factor-23 and Risk of Incident Chronic Kidney
Disease in Older Community-Dwelling Women
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; FGF-23; FGF23; PROGRESSION; MORTALITY;
EQUATION
AB Background and objectives Elevated circulating fibroblast growth factor 23 (FGF23) predicts progression of CKD, but it is unknown whether circulating FGF23 independently predicts incident CKD. This study aimed to determine whether circulating FGF23 predicts incident CKD in community-dwelling women.
Design, setting, participants, & measurements This study examined the relationship of intact serum FGF23, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D), 25-hydroxyvitamin D (25[OH]D), parathyroid hormone, calcium, and phosphate with prevalent and incident CKD in 701 disabled women, >= 65 years of age, from the Women's Health and Aging Study I in Baltimore, Maryland, from 1993 to 1997. Incident CKD was defined as a low estimated GFR (eGFR) <60 ml/min per 1.73 m(2) only, low eGFR <60 ml/min per 1.73 m(2) and a >= 25% decline in eGFR from baseline, and an increase in serum creatinine (>= 0.4 mg/dl) at follow-up.
Results At baseline, 381 women (54.3%) had stage 3 CKD. Of 307 women without CKD at baseline, 63 (20.5%) developed stage 3 CKD over 24 months of follow-up. After excluding prevalent cases of CKD, FGF23 (per 1 SD increase) was associated with incident stage 3 CKD (hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.06, 2.16; P=0.02), low and declining eGFR (HR, 3.69; 95% CI, 1.68, 8.11; P=0.001), and increase in serum creatinine (HR, 5.35; 95%, CI, 1.27, 22.54; P=0.02) in respective multivariable Cox proportional hazards models adjusting for baseline eGFR, age, race, phosphate, 1,25-dihydroxyvitamin D(3), parathyroid hormone, and other potential confounders.
Conclusions Elevated FGF23 is an independent risk factor for incident CKD in older, disabled, community-dwelling women. Clin J Am Soc. Nephrol 7: 85-91, 2012. doi:10.2215/CJN.08070811
C1 [Semba, Richard D.; Sun, Kai; Dalal, Mansi; Crasto, Candace] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Fink, Jeffrey C.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA.
[Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
OI Fink, Jeffrey/0000-0002-5622-5052
FU National Institutes of Health [R01AG027012, R01AG029148, R37AG019905];
National Institute on Aging, National Institutes of Health
FX This study was supported by Grants R01AG027012, R01AG029148, and
R37AG019905 from the National Institutes of Health, as well as the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health.
NR 28
TC 19
Z9 19
U1 0
U2 11
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JAN
PY 2012
VL 7
IS 1
BP 85
EP 91
DI 10.2215/CJN.08070811
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 877RD
UT WOS:000299198700015
PM 22076875
ER
PT J
AU Shastri, S
Tangri, N
Tighiouart, H
Beck, GJ
Vlagopoulos, P
Ornt, D
Eknoyan, G
Kusek, JW
Herzog, C
Cheung, AK
Sarnak, MJ
AF Shastri, Shani
Tangri, Navdeep
Tighiouart, Hocine
Beck, Gerald J.
Vlagopoulos, Panagiotis
Ornt, Daniel
Eknoyan, Garabed
Kusek, John W.
Herzog, Charles
Cheung, Alfred K.
Sarnak, Mark J.
TI Predictors of Sudden Cardiac Death: A Competing Risk Approach in the
Hemodialysis Study
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID BODY-MASS INDEX; MAINTENANCE HEMODIALYSIS; DIALYSIS PATIENTS;
RENAL-DISEASE; VASCULAR CALCIFICATION; CARDIOVASCULAR-DISEASE;
COMORBIDITY ASSESSMENT; ALKALINE-PHOSPHATASE; SERUM CREATININE;
MORTALITY RISK
AB Background and objectives There are few data on risk factors for sudden cardiac death (SCD) in patients undergoing hemodialysis (HD). The study objective was to identify predictors associated with various causes of death in the Hemodialysis (HEMO) Study and to develop a prediction model for SCD using a competing risk approach.
Design, setting, participants, & measurements In this analysis of 1745 HEMO participants, all-cause mortality was classified as SCD, non-SCD, and noncardiac death. Predictors for each cause of death were evaluated using cause-specific Cox proportional hazards models, and a competing risk approach was used to calculate absolute risk predictions for SCD.
Results During a median follow-up of 2.5 years, 808 patients died. Rates of SCD, non-SCD, and noncardiac death were 22%, 17%, and 61%, respectively. Predictors of various causes of death differ somewhat in HD patients. Age, diabetes, peripheral vascular disease, ischemic heart disease, serum creatinine, and alkaline phosphatase were independent predictors of SCD. The 3-year C-statistic for SCD was 0.75 (95% confidence interval, 0.70-0.79), and calibration was good (chi(2)=1.1; P=0.89). At years 3 and 5 of follow-up, the standard Cox model overestimated the risk for SCD as compared with the competing risk approach on the relative scale by 25% and 46%, respectively, and on the absolute scale by 2% and 6%, respectively.
Conclusions Predictors of various causes of death differ in HD patients. The proposed prediction model for SCD accounts for competing causes of death. External validation of this model is required. Clin J Am Soc Nephrol 7: 123-130, 2012. doi: 10.2215/CJN.06320611
C1 [Shastri, Shani; Tangri, Navdeep; Vlagopoulos, Panagiotis; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA.
[Tighiouart, Hocine] Tufts Med Ctr, Biostat Res Ctr, Boston, MA 02111 USA.
[Beck, Gerald J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Ornt, Daniel] Case Western Reserve Sch Med, Cleveland, OH USA.
[Eknoyan, Garabed] Baylor Coll Med, Houston, TX 77030 USA.
[Kusek, John W.] NIH, Bethesda, MD 20892 USA.
[Herzog, Charles] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Cheung, Alfred K.] Univ Utah, Salt Lake City, UT USA.
[Cheung, Alfred K.] Vet Affairs Salt Lake City Healthcare Syst, Salt Lake City, UT USA.
RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA.
EM msarnak@tuftsmedicalcenter.org
OI Tangri, Navdeep/0000-0002-5075-6370
FU National Institutes of Health [T32 DK07777, K24 DK078204]; Johnson
Johnson; National Institutes of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health
FX The study was funded by National Institutes of Health Grants T32 DK07777
and K24 DK078204.; C.H. served as a consultant for Amgen, Abbott,
Affymax, and Fibrogen; has an equity interest in Cambridge Heart and
Boston Scientific; and has received research support from Johnson &
Johnson and the National Institutes of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health.
NR 41
TC 22
Z9 25
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JAN
PY 2012
VL 7
IS 1
BP 123
EP 130
DI 10.2215/CJN.06320611
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 877RD
UT WOS:000299198700020
PM 22076880
ER
PT J
AU Biancotto, A
Dagur, PK
Fuchs, JC
Langweiler, M
McCoy, JP
AF Biancotto, Angelique
Dagur, Pradeep K.
Fuchs, J. Chris
Langweiler, Marc
McCoy, J. Philip, Jr.
TI OMIP-004: In-depth characterization of human T regulatory cells
SO CYTOMETRY PART A
LA English
DT Editorial Material
DE human; T cells; Treg
ID EXPRESSION; DIFFERENTIATION; SUBSETS
C1 [Biancotto, Angelique; Dagur, Pradeep K.; Fuchs, J. Chris; Langweiler, Marc; McCoy, J. Philip, Jr.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
RP McCoy, JP (reprint author), 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA.
EM mccoyjp@mail.nih.gov
FU Intramural NIH HHS [ZIC HL005905-02]
NR 7
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD JAN
PY 2012
VL 81A
IS 1
BP 15
EP 16
DI 10.1002/cyto.a.21158
PG 2
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 862KH
UT WOS:000298089100007
PM 22052639
ER
PT J
AU Rajagopalan, S
Nepa, J
Venkatachalam, S
AF Rajagopalan, Sangeetha
Nepa, Justin
Venkatachalam, Sundaresan
TI Chromodomain helicase DNA-binding protein 2 affects the repair of X-ray
and UV-Induced DNA damage
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE chromatin remodeling; Chd2; DNA repair; UVC; X-ray
ID DOUBLE-STRAND BREAKS; NUCLEOTIDE EXCISION-REPAIR; HISTONE H2A;
SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; MAMMALIAN-CELLS; ATM;
INO80; PHOSPHORYLATION; TRANSCRIPTION
AB Eukaryotic cells have evolved a variety of parallel and redundant DNA damage response pathways that function in a coordinated fashion to prevent the fixation of DNA damage as mutations. Despite the wealth of knowledge on DNA damage signaling on downstream cellular events, the mechanisms of DNA damage recognition, DNA repair as well as DNA damage signaling in the context of chromatin is poorly understood. Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene. The Chd2 mutant mice are highly susceptible to spontaneous lymphoid tumor formation. In this study, we present evidence that the Chd2 mutant cells are defective in their ability to repair DNA damage induced by ionizing and ultraviolet radiation. Consistent with the role of Chd2 in regulating DNA damage responses, the Chd2 mutant cells are also sensitive to DNA damaging agents in clonogenic assays. In summary, our data suggest that the Chd2 protein is involved in regulating the DNA damage responses at the chromatin level. Environ. Mol. Mutagen. 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Rajagopalan, Sangeetha; Nepa, Justin; Venkatachalam, Sundaresan] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN USA.
RP Venkatachalam, S (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
EM sundar@utk.edu
FU NIH [5R03CA133761]; Leukemia Research Foundation; PMERF Foundation
FX Grant sponsor: NIH; Grant number: 5R03CA133761; Grant sponsors: Leukemia
Research Foundation and PMERF Foundation.
NR 39
TC 8
Z9 8
U1 2
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JAN
PY 2012
VL 53
IS 1
BP 44
EP 50
DI 10.1002/em.20674
PG 7
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 872ZK
UT WOS:000298849900005
PM 22223433
ER
PT J
AU Theodore, WH
Wiggs, EA
Martinez, AR
Dustin, IH
Khan, OI
Appel, S
Reeves-Tyer, P
Sato, S
AF Theodore, William H.
Wiggs, Edythe A.
Martinez, Ashley R.
Dustin, Irene H.
Khan, Omar I.
Appel, Shmuel
Reeves-Tyer, Pat
Sato, Susumu
TI Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy
SO EPILEPSIA
LA English
DT Article
DE Serotonin receptors; Temporal lobe epilepsy; Memory; Depression; PET
scanning
ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE TRYPTOPHAN DEPLETION; 5-HT1A
RECEPTOR; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; ALZHEIMERS-DISEASE;
TREATMENT RESPONSE; BINDING; PET; COGNITION
AB Purpose: Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (PET) studies have shown reduced mesial temporal 5HT1A-receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A-receptor binding measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study.
Methods: We studied 40 patients (24 male; mean age 34.5 +/- 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video- electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1).
Key Findings: Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 +/- 27.3 vs. 95.4 +/- 28.4; p < 0.001). We found a significant relation between both left hippocampal 18FCWAY V/f1 (r = 0.41; p < 0.02) and left hippocampal volume (r = 0.36; p < 0.03) and delayed auditory memory score. On multiple regression, there was a significant effect of the interaction of left hippocampal 18FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 +/- 7.0. There was a significant inverse relation between BDI and 18FCWAY V/f1 ipsilateral to the patient's epileptic focus (r = 0.38 p < 0.02). There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory.
Significance: Our study suggests that reduced left hippocampal 5HT1A- receptor binding may play a role in memory impairment in patients with TLE.
C1 [Theodore, William H.; Martinez, Ashley R.; Dustin, Irene H.; Khan, Omar I.; Reeves-Tyer, Pat] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Wiggs, Edythe A.] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Appel, Shmuel; Sato, Susumu] NINDS, EEG Lab, NIH, Bethesda, MD 20892 USA.
RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10 Room 7C-103, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
FU NINDS NIH Division of Intramural Research
FX Supported by NINDS NIH Division of Intramural Research. We thank Dr
Sungyoung Auh for statistical advice.
NR 42
TC 22
Z9 25
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JAN
PY 2012
VL 53
IS 1
BP 129
EP 133
DI 10.1111/j.1528-1167.2011.03309.x
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 872DZ
UT WOS:000298790100020
PM 22050514
ER
PT J
AU White, HS
Alex, AB
Pollock, A
Hen, N
Shekh-Ahmad, T
Wilcox, KS
McDonough, JH
Stables, JP
Kaufmann, D
Yagen, B
Bialer, M
AF White, H. Steve
Alex, Anitha B.
Pollock, Amanda
Hen, Naama
Shekh-Ahmad, Tawfeeq
Wilcox, Karen S.
McDonough, John H.
Stables, James P.
Kaufmann, Dan
Yagen, Boris
Bialer, Meir
TI A new derivative of valproic acid amide possesses a broad-spectrum
antiseizure profile and unique activity against status epilepticus and
organophosphate neuronal damage
SO EPILEPSIA
LA English
DT Article
DE New anticonvulsant drug; Status epilepticus; Pilocarpine-induced SE rat
model; Soman-induced SE rat model; Pharmacokinetic-pharmacodynamic
correlation
ID TEMPORAL-LOBE EPILEPSY; PILOCARPINE MODEL; INDUCED NEUROPATHOLOGY;
SEIZURES; DIAZEPAM; BRAIN; SOMAN; RATS; EPILEPTOGENESIS; LEVETIRACETAM
AB Purpose: sec-Butyl-propylacetamide (SPD) is a one-carbon homolog of valnoctamide (VCD), a central nervous system (CNS)active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The study reported herein evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death.
Methods: The anticonvulsant activity of SPD was evaluated in several rodent seizure and epilepsy models, including maximal electroshock (MES), 6-Hz psychomotor; subcutaneous (s. c.) metrazol-, s. c. picrotoxin, s. c. bicuculline, and audiogenic, corneal, and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post-SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i. p.) administration in the soman SE rat model.
Key Findings: SPD was highly effective and displayed a wide protective index (PI = median neurotoxic dose/median effective dose [TD50/ED50]) in the standardized seizure and epilepsy models employed. The wide PI values of SPD demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also displayed anticonvulsant activity in the rat pilocarpine model of SE. Thirty minutes after the induction of SE, the calculated rat ED50 for SPD against convulsive SE in this model was 84 mg/kg. SPD was not neuroprotective in the organotypic hippocampal slice preparation; however, it did display hippocampal neuroprotection in both SE models and cognitive sparing in the MWM, which was associated with its antiseizure effect against pilocarpineinduced SE. When administered 20 and 40 min after SE onset, SPD (100-174 mg/kg) produced long-lasting efficacy (e. g., 4-8 h) against soman-induced convulsive and electrographic SE in both rats and guinea pigs. SPD ED50 values in guinea pigs were 67 and 92 mg/kg when administered at SE onset or 40 min after SE onset, respectively. Assuming linear pharmacokinetics (PK), the PK-PD (pharmacodynamic) results (rats) suggests that effective SPD plasma levels ranged between 8 and 40 mg/L (20 min after the onset of soman-induced seizures) and 12-50 mg/ L (40 min after the onset of soman-induced seizures). The time to peak (tmax) pharmacodynamic effect (PD-tmax) occurred after the PK-tmax, suggesting that SPD undergoes slow distribution to extraplasmatic sites, which is likely responsible for antiseizure activity of SPD.
Significance: The results demonstrate that SPD is a broad-spectrum antiseizure compound that blocks SE induced by pilocarpine and soman and affords in vivo neuroprotection that is associated with cognitive sparing. Its activity against SE is superior to that of diazepam in terms of rapid onset, potency, and its effect on animal mortality and functional improvement.
C1 [Hen, Naama; Shekh-Ahmad, Tawfeeq; Kaufmann, Dan; Yagen, Boris; Bialer, Meir] Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, Fac Med, IL-91120 Jerusalem, Israel.
[White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Wilcox, Karen S.] Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Anticonvulsant Drug Dev Program, Salt Lake City, UT 84112 USA.
[McDonough, John H.] USA, Med Res Inst Chem Def, Pharmacol Branch, Div Res, Aberdeen Proving Ground, MD 21010 USA.
[Stables, James P.] NINDS, ASP, Off Translat Res, NIH, Bethesda, MD 20892 USA.
[Yagen, Boris; Bialer, Meir] Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel.
RP Bialer, M (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, Fac Med, IL-91120 Jerusalem, Israel.
EM bialer@md.huji.ac.il
FU NINDS, NIH [NO1-NS-4-2359]; NIH/NINDS [Y1-O6-9613-01]; USAMRICD
[A120-B.P2009-2]; Defense Threat Reduction Agency - Joint Science and
Technology Office, Medical ST Division
FX Studies conducted at the University of Utah were supported by NINDS, NIH
Contract No. NO1-NS-4-2359 (HSW, ABA, KSW, ALP). The studies conducted
at MRICD were supported by an Inter-Agency Agreement between NIH/NINDS
(Y1-O6-9613-01) and USAMRICD (A120-B.P2009-2) and the Defense Threat
Reduction Agency - Joint Science and Technology Office, Medical S&T
Division. The views expressed in this paper are those of the authors and
do not reflect the official policy of the Department of Army, Department
of Defense, or the U.S. Government.
NR 44
TC 35
Z9 35
U1 1
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JAN
PY 2012
VL 53
IS 1
BP 134
EP 146
DI 10.1111/j.1528-1167.2011.03338.x
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 872DZ
UT WOS:000298790100021
PM 22150444
ER
PT J
AU Gugger, OS
Hartmann, J
Birnbaumer, L
Kapfhammer, JP
AF Gugger, Olivia S.
Hartmann, Jana
Birnbaumer, Lutz
Kapfhammer, Josef P.
TI P/Q-type and T-type calcium channels, but not type 3 transient receptor
potential cation channels, are involved in inhibition of dendritic
growth after chronic metabotropic glutamate receptor type 1 and protein
kinase C activation in cerebellar Purkinje cells
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cerebellar organotypic slice cultures; dendritic development; dendritic
growth; mouse
ID ORGANOTYPIC SLICE CULTURES; CA2+ CHANNELS; PERIPHERAL NEURONS;
PHOSPHOLIPASE-C; TRPC3 CHANNELS; EXPRESSION; CURRENTS; MICE; ANTAGONIST;
MUTATION
AB The development of a neuronal dendritic tree is modulated both by signals from afferent fibers and by an intrinsic program. We have previously shown that chronic activation of either type 1 metabotropic glutamate receptors (mGluR1s) or protein kinase C (PKC) in organotypic cerebellar slice cultures of mice and rats severely inhibits the growth and development of the Purkinje cell dendritic tree. The signaling events linking receptor activation to the regulation of dendritic growth remain largely unknown. We have studied whether channels allowing the entry of Ca2+ into Purkinje cells, in particular the type 3 transient receptor potential cation channels (TRPC3s), P/Q-type Ca2+ channels, and T-type Ca2+ channels, might be involved in signaling after mGluR1 or PKC stimulation. We show that the inhibition of dendritic growth seen after mGluR1 or PKC stimulation is partially rescued by pharmacological blockade of P/Q-type and T-type Ca2+ channels, indicating that activation of these channels mediating Ca2+ influx contributes to the inhibition of dendritic growth. In contrast, the absence of Ca2+ -permeable TRPC3s in TRPC3-deficient mice or pharmacological blockade had no effect on mGluR1-mediated and PKC-mediated inhibition of Purkinje cell dendritic growth. Similarly, blockade of Ca2+ influx through glutamate receptor d2 or R-type Ca2+ channels or inhibition of release from intracellular stores did not influence mGluR1-mediated and PKC-mediated inhibition of Purkinje cell dendritic growth. These findings suggest that both T-type and P/Q-type Ca2+ channels, but not TRPC3 or other Ca2+-permeable channels, are involved in mGluR1 and PKC signaling leading to the inhibition of dendritic growth in cerebellar Purkinje cells.
C1 [Gugger, Olivia S.; Kapfhammer, Josef P.] Univ Basel, Inst Anat, Dept Biomed Basel, CH-4056 Basel, Switzerland.
[Hartmann, Jana] Tech Univ Munich, Inst Neurosci, Munich, Germany.
[Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Kapfhammer, JP (reprint author), Univ Basel, Inst Anat, Dept Biomed Basel, Pestalozzistr 20, CH-4056 Basel, Switzerland.
EM Josef.Kapfhammer@unibas.ch
RI Hartmann, Jana/C-1024-2008
FU University of Basel; Swiss National Science Foundation [31003A-116624]
FX We thank Markus Saxer for technical assistance. This work was supported
by the University of Basel and the Swiss National Science Foundation
(31003A-116624).
NR 45
TC 6
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JAN
PY 2012
VL 35
IS 1
BP 20
EP 33
DI 10.1111/j.1460-9568.2011.07942.x
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 871KR
UT WOS:000298737500003
PM 22188405
ER
PT J
AU Vivar, C
Traub, RD
Gutierrez, R
AF Vivar, Carmen
Traub, Roger D.
Gutierrez, Rafael
TI Mixed electrical-chemical transmission between hippocampal mossy fibers
and pyramidal cells
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE CA3; electrical communication; mixed transmission; mossy fibers; rat;
spikelets
ID LONG-TERM POTENTIATION; RAT DENTATE GYRUS; SYNAPTIC-TRANSMISSION;
GRANULE CELLS; IN-VITRO; SYNAPSES; NEURONS; INTERNEURONS; OSCILLATIONS;
NETWORK
AB Morphological and electrophysiological studies have shown that granule cell axons, the mossy fibers (MFs), establish gap junctions and therefore electrical communication among them. That granule cells express gap junctional proteins in their axons suggests the possibility that their terminals also express them. If this were to be the case, mixed electricalchemical communication could be supported, as MF terminals normally use glutamate for fast communication with their target cells. Here we present electrophysiological studies in the rat and modeling studies consistent with this hypothesis. We show that MF activation produced fast spikelets followed by excitatory postsynaptic potentials in pyramidal cells (PCs), which, unlike the spikelets, underwent frequency potentiation and were strongly depressed by activation of metabotropic glutamate receptors, as expected from transmission of MF origin. The spikelets, which persisted during blockade of chemical transmission, were potentiated by dopamine and suppressed by the gap junction blocker carbenoxolone. The various waveforms evoked by MF stimulation were replicated in a multi-compartment model of a PC by brief current-pulse injections into the proximal apical dendritic compartment, where MFs are known to contact PCs. Mixed electrical and glutamatergic communication between granule cells and some PCs in CA3 may ensure the activation of sets of PCs, bypassing the strong action of concurrent feed-forward inhibition that granule cells activate. Importantly, MF-to-PC electrical coupling may allow bidirectional, possibly graded, communication that can be faster than chemical synapses and subject to different forms of modulation.
C1 [Vivar, Carmen] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Physiol Biophys & Neurosci, Mexico City, DF, Mexico.
[Traub, Roger D.] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA.
[Gutierrez, Rafael] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Pharmacobiol, Mexico City 14330, DF, Mexico.
RP Gutierrez, R (reprint author), NIA, NIH, Biomed Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA.
EM rafagut@cinvestav.mx
OI Gutierrez, Rafael/0000-0002-6566-3900
FU Consejo Nacional de Ciencia y Tecnologia [45754,
I020/193/10FON.INST.-29-10]; NINDS/NIH [RO1NS44133]
FX We thank D. Schmitz and A. Draguhn for valuable comments during the
execution of this project. The postdoctoral fellowship to C. V. and this
study were supported by grants to R. G. (45754 and
I020/193/10FON.INST.-29-10 from Consejo Nacional de Ciencia y
Tecnologia). R. D. T. was supported by NINDS/NIH RO1NS44133. Part of
this investigation was conducted while R. G. was a member of the
Department of Physiology, Biophysics and Neurosciences.
NR 44
TC 19
Z9 19
U1 2
U2 11
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 JAN
PY 2012
VL 35
IS 1
BP 76
EP 82
DI 10.1111/j.1460-9568.2011.07930.x
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 871KR
UT WOS:000298737500008
PM 22151275
ER
PT J
AU Bang, SJ
Jensen, P
Dymecki, SM
Commons, KG
AF Bang, Sun Jung
Jensen, Patricia
Dymecki, Susan M.
Commons, Kathryn G.
TI Projections and interconnections of genetically defined serotonin
neurons in mice
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dorsal raphe; feedback inhibition; median raphe; rhombomere; serotonin;
serotonin1A receptor
ID DORSAL RAPHE NUCLEUS; AXON TERMINALS; SUPRACHIASMATIC NUCLEUS;
CEREBRAL-CORTEX; RAT; SYSTEM; ORGANIZATION; STIMULATION; INNERVATION;
ACTIVATION
AB Brain serotonin neurons are heterogeneous and can be distinguished by several anatomical and physiological characteristics. Toward resolving this heterogeneity into classes of functional relevance, subtypes of mature serotonin neurons were previously identified based on gene expression differences initiated during development in different rhombomeric (r) segments of the hindbrain. This redefinition of mature serotonin neuron subtypes based on the criteria of genetic lineage, along with the enabling genetic fate mapping tools, now allows various functional properties, such as axonal projections, to be allocated onto these identified subtypes. Furthermore, our approach uniquely enables interconnections between the different serotonin neuron subtypes to be determined; this is especially relevant because serotonin neuron activity is regulated by several feedback mechanisms. We used intersectional and subtractive genetic fate mapping tools to generate three independent lines of mice in which serotonin neurons arising in different rhombomeric segments, either r1, r2 or both r3 and r5, were uniquely distinguished from all other serotonin neurons by their expression of enhanced green fluorescent protein. Each of these subgroups of serotonergic neurons had a unique combination of forebrain projection targets. Typically more than one subgroup innervated an individual target area. Unique patterns of interconnections between the different groups of serotonin neurons were also observed and these pathways could subserve feedback regulatory circuits. Overall, the current findings suggest that activation of subsets of serotonin neurons could result in topographic serotonin release in the forebrain coupled with feedback inhibition of serotonin neurons with alternative projection targets.
C1 [Bang, Sun Jung; Commons, Kathryn G.] Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA.
[Bang, Sun Jung; Commons, Kathryn G.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
[Jensen, Patricia] NIEHS, Neurobiol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Dymecki, Susan M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Commons, KG (reprint author), Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM kathryn.commons@childrens.harvard.edu
FU NIH [P01-HD036379, R21-DA023643, R01-DA021801]; Charles H. Hood
Foundation (Boston, MA); William Randolph Hearst Fund; NIH, National
Institute of Environmental Health Sciences
FX This work was supported by grants from NIH P01-HD036379, R21-DA023643,
R01-DA021801, Charles H. Hood Foundation (Boston, MA), William Randolph
Hearst Fund and the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences.
NR 38
TC 51
Z9 51
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JAN
PY 2012
VL 35
IS 1
BP 85
EP 96
DI 10.1111/j.1460-9568.2011.07936.x
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 871KR
UT WOS:000298737500010
PM 22151329
ER
PT J
AU Harris, PJ
Speranza, G
Ullmann, CD
AF Harris, Pamela Jo
Speranza, Giovanna
Ullmann, Claudio Dansky
TI Targeting embryonic signaling pathways in cancer therapy
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Review
DE cancer; cancer stem cells; developmental pathways; embryonic signaling
pathways; Hedgehog; Notch; Wnt
ID SMALL-MOLECULE ANTAGONISTS; INHIBITS TUMOR-GROWTH; BASAL-CELL CARCINOMA;
ACUTE LYMPHOBLASTIC-LEUKEMIA; GAMMA-SECRETASE INHIBITORS; HUMAN
BREAST-CANCER; HEDGEHOG PATHWAY; LUNG-CANCER; STEM-CELLS; BETA-CATENIN
AB Introduction: The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed.
Areas covered: This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field.
Expert opinion: CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.
C1 [Ullmann, Claudio Dansky] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Harris, Pamela Jo] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Speranza, Giovanna] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Ullmann, CD (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, 6130 Execut Blvd,Execut Plaza N,Suite 7030, Bethesda, MD 20892 USA.
EM danskyullc@mail.nih.gov
NR 112
TC 19
Z9 19
U1 0
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8222
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD JAN
PY 2012
VL 16
IS 1
BP 131
EP 145
DI 10.1517/14728222.2011.645808
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 876FH
UT WOS:000299092400011
PM 22239436
ER
PT J
AU Gahl, WA
Markello, TC
Toro, C
Fajardo, KF
Sincan, M
Gill, F
Carlson-Donohoe, H
Gropman, A
Pierson, TM
Golas, G
Wolfe, L
Groden, C
Godfrey, R
Nehrebecky, M
Wahl, C
Landis, DMD
Yang, S
Madeo, A
Mullikin, JC
Boerkoel, CF
Tifft, CJ
Adams, D
AF Gahl, William A.
Markello, Thomas C.
Toro, Camilo
Fajardo, Karin Fuentes
Sincan, Murat
Gill, Fred
Carlson-Donohoe, Hannah
Gropman, Andrea
Pierson, Tyler Mark
Golas, Gretchen
Wolfe, Lynne
Groden, Catherine
Godfrey, Rena
Nehrebecky, Michele
Wahl, Colleen
Landis, Dennis M. D.
Yang, Sandra
Madeo, Anne
Mullikin, James C.
Boerkoel, Cornelius F.
Tifft, Cynthia J.
Adams, David
CA NISC Comparative Sequencing Progr
TI The National Institutes of Health Undiagnosed Diseases Program: insights
into rare diseases
SO GENETICS IN MEDICINE
LA English
DT Article
DE neurological disorders; rare disease; SNP arrays; undiagnosed disease;
whole exome sequencing
ID PARAPLEGIN MUTATIONS; GENE
AB Purpose: This report describes the National Institutes of Health Undiagnosed Diseases Program, details the Program's application of genomic technology to establish diagnoses, and details the Program's success rate during its first 2 years.
Methods: Each accepted study participant was extensively phenotyped. A subset of participants and selected family members (29 patients and 78 unaffected family members) was subjected to an integrated set of genomic analyses including high-density single-nucleotide polymorphism arrays and whole exome or genome analysis.
Results: Of 1,191 medical records reviewed, 326 patients were accepted and 160 were admitted directly to the National Institutes of Health Clinical Center on the Undiagnosed Diseases Program service. Of those, 47% were children, 55% were females, and 53% had neurologic disorders. Diagnoses were reached on 39 participants (24%) on clinical, biochemical, pathologic, or molecular grounds; 21 diagnoses involved rare or ultra-rare diseases. Three disorders were diagnosed based on single-nucleotide polymorphism array analysis and three others using whole exome sequencing and filtering of variants. Two new disorders were discovered. Analysis of the single-nucleotide polymorphism array study cohort revealed that large stretches of homozygosity were more common in affected participants relative to controls.
Conclusion: The National Institutes of Health Undiagnosed Diseases Program addresses an unmet need, i.e., the diagnosis of patients with complex, multisystem disorders. It may serve as a model for the clinical application of emerging genomic technologies and is providing insights into the characteristics of diseases that remain undiagnosed after extensive clinical workup.
C1 [Gahl, William A.; Toro, Camilo; Fajardo, Karin Fuentes; Pierson, Tyler Mark; Wolfe, Lynne; Groden, Catherine; Godfrey, Rena; Nehrebecky, Michele; Wahl, Colleen; Landis, Dennis M. D.; Yang, Sandra; Boerkoel, Cornelius F.; Tifft, Cynthia J.; Adams, David] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
[Gahl, William A.; Markello, Thomas C.; Gropman, Andrea; Golas, Gretchen; Groden, Catherine; Yang, Sandra; Tifft, Cynthia J.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Gahl, William A.; Sincan, Murat; Carlson-Donohoe, Hannah; Adams, David] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Gill, Fred] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Gropman, Andrea] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Pierson, Tyler Mark] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA.
[Madeo, Anne] NIH, Social & Behav Res Branch, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
[Mullikin, James C.] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Adams, D (reprint author), NIH, Undiagnosed Dis Program, Bldg 10, Bethesda, MD 20892 USA.
EM david.adams@nih.gov
RI Madeo, Anne/K-2880-2012
FU Intramural Division of the National Human Genome Research Institute;
National Institute of Neurological Disorders and Stroke; NIH Clinical
Center; NIH Office of the Director; Office of Rare Diseases Research;
National Human Genome Research Institute and the National Institute of
Neurological Disorders and Stroke
FX This work was supported by the Intramural Division of the National Human
Genome Research Institute and the National Institute of Neurological
Disorders and Stroke, the NIH Clinical Center, the NIH Office of the
Director, the Office of Rare Diseases Research (Dr Stephen Groft), the
NIH Clinical Center (Dr John Gallin), and the Intramural Research
Programs of the National Human Genome Research Institute and the
National Institute of Neurological Disorders and Stroke. The authors
thank the NIH UDP patients, their families, and their physicians for
making this enterprise a truly united effort; Roxanne Fischer and
Richard Hess for their excellent technical assistance and the entire UDP
staff for their dedicated service; and the NIH Intramural Sequencing
Center for performing the whole exome and whole genome sequencing and
analysis. The NHGRI Genomics Core provided superb SNP array results.
NR 31
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U1 1
U2 3
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 JAN
PY 2012
VL 14
IS 1
BP 51
EP 59
DI 10.1038/gim.0b013e318232a005
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 873NI
UT WOS:000298889600005
PM 22237431
ER
PT J
AU Hsu, AP
Dowdell, KC
Davis, J
Niemela, JE
Anderson, SM
Shaw, PA
Rao, VK
Puck, JM
AF Hsu, Amy P.
Dowdell, Kennichi C.
Davis, Joie
Niemela, Julie E.
Anderson, Stacie M.
Shaw, Pamela A.
Rao, V. Koneti
Puck, Jennifer M.
TI Autoimmune lymphoproliferative syndrome due to FAS mutations outside the
signal-transducing death domain: molecular mechanisms and clinical
penetrance
SO GENETICS IN MEDICINE
LA English
DT Article
DE autoimmune lymphoproliferative syndrome; FAS; genotype-phenotype
correlation; haploinsufficiency; penetrance
ID CELL-DEATH; MESSENGER-RNA; SYNDROME ALPS; CD95; APOPTOSIS; DOMINANT;
GENE; COMPLEX; SITE; TRANSPLANTATION
AB Purpose: Autoimmune lymphoproliferative syndrome is a disorder of lymphocyte apoptosis. Although FAS molecules bearing mutations in the signal-transducing intracellular death domain exhibit dominant-negative interference with FAS-mediated apoptosis, mechanisms for pathology of non-death domain FAS mutations causing autoimmune lymphoproliferative syndrome are poorly defined.
Methods: RNA stability, protein expression, ligand binding, and ability to transmit apoptosis signals by anti-FAS antibody or FAS ligand were determined for a cohort of 39 patients with non-death domain autoimmune lymphoproliferative syndrome. Correlations between mutation type and disease penetrance were established in mutation-positive family members.
Results: Frameshifts or transcriptional stop mutations before exon 7 resulted in messenger RNA haploinsufficiency, whereas an amino-terminal signal sequence mutation and certain intracellular truncations prevented cell surface localization of FAS. All resulted in decreased FAS localization, inability to bind FAS ligand, and reduced FAS ligand-induced apoptosis. Extracellular missense mutations and in-frame deletions expressed defective FAS protein, failed to bind FAS ligand, and exhibited dominant-negative interference with FAS-mediated apoptosis. Mutation-positive relatives with haploinsufficient or extracellular mutations had lower penetrance of autoimmune lymphoproliferative syndrome clinical phenotypes than did relatives with death domain mutations.
Conclusion: We have defined molecular mechanisms by which non-death domain FAS mutations result in reduced lymphocyte apoptosis, established a hierarchy of genotype-phenotype correlation among mutation-positive relatives of patients with autoimmune lymphoproliferative syndrome, and demonstrated that FAS haploinsufficiency can lead to autoimmune lymphoproliferative syndrome.
C1 [Hsu, Amy P.; Davis, Joie; Rao, V. Koneti] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Dowdell, Kennichi C.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Niemela, Julie E.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
[Anderson, Stacie M.] NHGRI, Bethesda, MD 20892 USA.
[Shaw, Pamela A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
RP Hsu, AP (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twins@niaid.nih.gov
OI Niemela, Julie/0000-0003-4197-3792
FU National Institutes of Health, National Human Genome Research Institute,
and National Institute of Allergy and Infectious Disease, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Human Genome Research Institute,
and National Institute of Allergy and Infectious Disease, Bethesda, MD
20892. The authors thank the patients and their families, Roxanne E.
Fischer for her valuable contributions related to sample processing, Tom
Fleisher and Janet Dale for phenotypic delineation, and Mike Lenardo and
the late Stephen Straus for their helpful discussions.
NR 36
TC 9
Z9 12
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2012
VL 14
IS 1
BP 81
EP 89
DI 10.1038/gim.0b013e3182310b7d
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 873NI
UT WOS:000298889600009
PM 22237435
ER
PT J
AU Bellcross, CA
Bedrosian, SR
Daniels, E
Duquette, D
Hampel, H
Jasperson, K
Joseph, DA
Kaye, C
Lubin, I
Meyer, LJ
Reyes, M
Scheuner, MT
Schully, SD
Senter, L
Stewart, SL
St Pierre, J
Westman, J
Wise, P
Yang, VW
Khoury, MJ
AF Bellcross, Cecelia A.
Bedrosian, Sara R.
Daniels, Elvan
Duquette, Debra
Hampel, Heather
Jasperson, Kory
Joseph, Djenaba A.
Kaye, Celia
Lubin, Ira
Meyer, Laurence J.
Reyes, Michele
Scheuner, Maren T.
Schully, Sheri D.
Senter, Leigha
Stewart, Sherri L.
St Pierre, Jeanette
Westman, Judith
Wise, Paul
Yang, Vincent W.
Khoury, Muin J.
TI Implementing screening for Lynch syndrome among patients with newly
diagnosed colorectal cancer: summary of a public health/clinical
collaborative meeting
SO GENETICS IN MEDICINE
LA English
DT Article
DE colorectal cancer; genetic screening; genetic testing; HNPCC; Lynch
syndrome
ID CUMULATIVE LIFETIME INCIDENCE; GENETIC TESTING STRATEGIES; MISMATCH
REPAIR PROTEINS; EGAPP WORKING GROUP; MICROSATELLITE INSTABILITY;
ENDOMETRIAL CANCER; REDUCING MORBIDITY; MUTATION CARRIERS; PROVEN
MUTATIONS; MLH1 PROMOTER
AB Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.
C1 [Bellcross, Cecelia A.; Bedrosian, Sara R.; Reyes, Michele; St Pierre, Jeanette; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Bellcross, Cecelia A.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Daniels, Elvan] Morehouse Sch Med, Natl Ctr Primary Care, Atlanta, GA 30310 USA.
[Duquette, Debra] Michigan Dept Community Hlth, Lansing, MI USA.
[Hampel, Heather; Senter, Leigha; Westman, Judith] Ohio State Univ, Dept Internal Med, Div Human Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Jasperson, Kory] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Joseph, Djenaba A.; Stewart, Sherri L.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
[Kaye, Celia] Univ Colorado, Off Educ Dev & Res, Sch Med, Aurora, CO USA.
[Lubin, Ira] Ctr Dis Control & Prevent, Lab Res & Evaluat Branch, Atlanta, GA USA.
[Meyer, Laurence J.] Salt Lake City Hlth Care Syst, Dept Vet Affairs, Salt Lake City, UT USA.
[Scheuner, Maren T.] Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Los Angeles, CA USA.
[Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Schully, Sheri D.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Wise, Paul] Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37240 USA.
[Yang, Vincent W.] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA USA.
RP Bellcross, CA (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
EM cbellcr@emory.edu
OI Wise, Paul/0000-0003-3798-7913
FU NCI NIH HHS [R01 CA084197]; NIDDK NIH HHS [R01 DK052230]
NR 62
TC 32
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2012
VL 14
IS 1
BP 152
EP 162
DI 10.1038/gim.0b013e31823375ea
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 873NI
UT WOS:000298889600019
PM 22237445
ER
PT J
AU Schully, SD
Benedicto, CB
Khoury, MJ
AF Schully, Sheri D.
Benedicto, Camilla B.
Khoury, Muin J.
TI How can we stimulate translational research in cancer genomics beyond
bench to bedside?
SO GENETICS IN MEDICINE
LA English
DT Letter
C1 [Schully, Sheri D.; Benedicto, Camilla B.; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Khoury, Muin J.] CDC, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
RP Schully, SD (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM schullys@mail.nih.gov
NR 6
TC 12
Z9 12
U1 0
U2 2
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 JAN
PY 2012
VL 14
IS 1
BP 169
EP 170
DI 10.1038/gim.2011.12
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 873NI
UT WOS:000298889600022
PM 22237448
ER
PT J
AU Fradkin, JE
AF Fradkin, Judith E.
TI Confronting The Urgent Challenge Of Diabetes: An Overview
SO HEALTH AFFAIRS
LA English
DT Article
ID LIFE-STYLE INTERVENTION; 10-YEAR FOLLOW-UP; CARDIOVASCULAR-DISEASE;
INSULIN-RESISTANCE; PREVENTION PROGRAM; MELLITUS; PREVALENCE; OBESITY;
YOUTH; HYPERGLYCEMIA
AB The rising tide of diabetes has an unacceptable human and societal toll. Rates of all major forms of diabetes are increasing at enormous individual and societal cost: 8.3 percent of the US population is afflicted today, and financial costs reached $174 billion for 2007. A major cause of blindness, renal failure, amputation, and cardiovascular disease, diabetes also increases the risk of cancer and dementia and more than doubles individual health care costs. Control of glucose, blood pressure, and lipids improves outcomes. Yet diabetes management is nonetheless suboptimal, particularly in disproportionately affected poor and minority populations. Safer, less burdensome, and more personalized approaches to therapy are needed. People at high risk for type 2 diabetes must be identified if society is to realize the benefits of therapies proven to delay or prevent the disease. We have many of the tools we need to address this challenge, and we must apply them now.
C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
RP Fradkin, JE (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
EM jf58s@nih.gov
NR 35
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U1 0
U2 4
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD JAN
PY 2012
VL 31
IS 1
BP 12
EP 19
DI 10.1377/hlthaff.2011.1150
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 879DD
UT WOS:000299309000003
PM 22232089
ER
PT J
AU Briassoulis, G
Quezado, M
Lee, CCR
Xekouki, P
Keil, M
Stratakis, CA
AF Briassoulis, George
Quezado, Martha
Lee, Chyi-Chia Richard
Xekouki, Paraskevi
Keil, Meg
Stratakis, Constantine A.
TI Myxoma of the ear lobe in a 23-month-old girl with Carney complex
SO JOURNAL OF CUTANEOUS PATHOLOGY
LA English
DT Article
DE Carney complex; ear tumors; pediatrics; PRKAR1A mutation; protein kinase
A
ID TUMORS
AB Myxomas of the ear are extremely uncommon, especially in young children. A 23-month-old girl born to a family with known Carney complex, a condition that predisposes to multiple myxomas, presented with a large, cauliflower-like mass located on the back of her right ear. Histopathologically, the lesion was composed of scattered spindle-shaped or stellate cells with abundant associated mucin and a very sparse inflammatory infiltrate containing lymphocytes and neutrophils. The patient was a carrier of a protein kinase A regulatory subunit 1A (PRKAR1A) mutation; PRKAR1A mutations cause Carney complex in most patients with this rare disorder. This is the earliest presentation of an ear lobe myxoma reported in the literature.
C1 [Briassoulis, George; Xekouki, Paraskevi; Keil, Meg; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Briassoulis, George] Univ Crete, Dept Pediat, Iraklion, Crete, Greece.
[Quezado, Martha; Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Keil, Meg; Stratakis, Constantine A.] NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); University of Crete, Heraklion, Crete, Greece
FX This study was supported by the Intramural Programs of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and, in part, by a sabbatical to Dr G. Briassoulis by the
University of Crete, Heraklion, Crete, Greece.
NR 10
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6987
J9 J CUTAN PATHOL
JI J. Cutan. Pathol.
PD JAN
PY 2012
VL 39
IS 1
BP 68
EP 71
DI 10.1111/j.1600-0560.2011.01786.x
PG 4
WC Dermatology; Pathology
SC Dermatology; Pathology
GA 869HF
UT WOS:000298588100015
PM 21880053
ER
PT J
AU Harazim, SM
Xi, W
Schmidt, CK
Sanchez, S
Schmidt, OG
AF Harazim, Stefan M.
Xi, Wang
Schmidt, Christine K.
Sanchez, Samuel
Schmidt, Oliver G.
TI Fabrication and applications of large arrays of multifunctional
rolled-up SiO/SiO2 microtubes
SO JOURNAL OF MATERIALS CHEMISTRY
LA English
DT Article
ID FLUIDIC RING-RESONATOR; CELLS; NANOTUBES; FILMS; NANOTECHNOLOGY;
SCAFFOLDS; ENGINES; TUBES
AB Biocompatible, multifunctional large arrays of transparent SiO/SiO2 microtubes are fabricated by rolled-up nanotech. The outer tubular diameter as a function of thicknesses of SiO and SiO2 has been systematically studied and the roll-up parameters have been optimized to deterministically achieve a yield of nearly 100%. A macroscopic continuum mechanical model is in good agreement with the experimental data. The relative ease in functionalization of the "glass'' microtubes with different biomaterials renders rolled-up nanotech an excellent option for various on- and off-chip applications, including optofluidic sensors, micro-engines and pre-patterned 3D scaffolds for cell culturing.
C1 [Harazim, Stefan M.; Xi, Wang; Sanchez, Samuel; Schmidt, Oliver G.] IFW Dresden, Inst Integrat Nanosci, D-01069 Dresden, Germany.
[Schmidt, Christine K.] NCI, NIH, Bethesda, MD 20892 USA.
[Schmidt, Oliver G.] Tech Univ Chemnitz, D-09107 Chemnitz, Germany.
RP Sanchez, S (reprint author), IFW Dresden, Inst Integrat Nanosci, Helmholtzstr 20, D-01069 Dresden, Germany.
EM s.sanchez@ifw-dresden.de
RI Sanchez, Samuel/B-6803-2015;
OI Sanchez, Samuel/0000-0002-5845-8941; Schmidt,
Christine/0000-0002-8363-7933
FU Volkswagen Foundation [I/84 072]; DFG Research Unit [1713]; U. S. Air
Force Office of Scientific Research (AFOSR) [FA9550-09-0550]; EMBO
FX This work was financially supported by the Volkswagen Foundation I/84
072, DFG Research Unit 1713 "Sensoric Micro- and Nanosystems and a
Multidisciplinary University Research Initiative (MURI) sponsored by the
U. S. Air Force Office of Scientific Research (AFOSR) (FA9550-09-0550)
and an EMBO long-term fellowship to CKS. Authors thank S. Kiravittaya
for supporting the calculation, B. Eichler for AFM scanning, R.
Engelhard and E. J. Smith for support in eBeam evaporation and
discussions and Dr Daniel Gerlich for supplying the HeLa Kyoto cell
line, stably expressing mEGFP-alpha-tubulin and H2B-mcherry. Dr Tom
Misteli is acknowledged for supporting the biological studies.
NR 54
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U2 36
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 0959-9428
J9 J MATER CHEM
JI J. Mater. Chem.
PY 2012
VL 22
IS 7
BP 2878
EP 2884
DI 10.1039/c1jm14800a
PG 7
WC Chemistry, Physical; Materials Science, Multidisciplinary
SC Chemistry; Materials Science
GA 881RI
UT WOS:000299504200012
ER
PT J
AU Kandiah, E
Watts, NR
Cheng, NG
Cardone, G
Stahl, SJ
Heller, T
Liang, TJ
Wingfield, PT
Steven, AC
AF Kandiah, Eaazhisai
Watts, Norman R.
Cheng, Naigian
Cardone, Giovanni
Stahl, Stephen J.
Heller, Theo
Liang, T. Jake
Wingfield, Paul T.
Steven, Alasdair C.
TI Cryo-EM study of Hepatitis B virus core antigen capsids decorated with
antibodies from a human patient
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Polyclonal antibodies; Antibody labeling; Molecular modeling;
Immunodominant epitopes; Conformational epitopes
ID CRYOELECTRON MICROSCOPY; MONOCLONAL-ANTIBODIES; ELECTRON-MICROGRAPHS;
ESCHERICHIA-COLI; PROTEINS; BINDING; FAB; EPITOPES; SURFACE;
COCRYSTALLIZATION
AB The capsid (core antigen, HBcAg) is one of three major antigens present in patients infected with Hepatitis B virus. The capsids are icosahedral particles, whose most prominent features are spikes that extend 25 angstrom out from the contiguous "floor". At the spike tip are two copies of the "immunodominant loop". Previously, the epitopes of seven murine monoclonal antibodies have been identified by cryo-EM analysis of Fab-labeled capsids. All but one are conformational and all but one map around the spike tip. The exception, which is also the tightest-binder, straddles an inter-molecular interface on the floor. Seeking to relate these observations to the immunological response of infected humans, we isolated anti-cAg antibodies from a patient, prepared Fabs, and analyzed their binding to capsids. A priori, one possibility was that many different Fabs would give an undifferentiated continuum of Fab-related density. In fact, the density observed was highly differentiated and could be reproduced by modeling with just five Fabs, three binding to the spike and two to the floor. These results show that epitopes on the floor, far (similar to 30 angstrom) from the immunodominant loop, are clinically relevant and that murine anti-cAg antibodies afford a good model for the human system. Published by Elsevier Inc.
C1 [Kandiah, Eaazhisai; Cheng, Naigian; Cardone, Giovanni; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Watts, Norman R.; Stahl, Stephen J.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA.
[Heller, Theo; Liang, T. Jake] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, 50 S Dr,Rm 1517, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU NIAMS; NIDDK
FX This research was supported by the Intramural Research Programs of NIAMS
and NIDDK.
NR 41
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U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD JAN
PY 2012
VL 177
IS 1
SI SI
BP 145
EP 151
DI 10.1016/j.jsb.2011.10.003
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 880ZK
UT WOS:000299448900019
PM 22056468
ER
PT J
AU Hartge, P
Speyer, JL
AF Hartge, Patricia
Speyer, James L.
TI Finding Ovarian Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID BREAST-CANCER; TUMOR SIZE; MORTALITY; PROSTATE; TRIAL; LUNG
C1 [Hartge, Patricia] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Speyer, James L.] NYU, Dept Med, Langone Med Ctr, Ctr Clin Canc,Canc Inst, New York, NY 10016 USA.
RP Hartge, P (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8090, Bethesda, MD 20892 USA.
EM hartgep@mail.nih.gov
FU Intramural NIH HHS
NR 10
TC 4
Z9 4
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN
PY 2012
VL 104
IS 2
BP 82
EP 83
DI 10.1093/jnci/djr518
PG 2
WC Oncology
SC Oncology
GA 879QF
UT WOS:000299346200001
PM 22247023
ER
PT J
AU Andriole, GL
Crawford, ED
Grubb, RL
Buys, SS
Chia, D
Church, TR
Fouad, MN
Isaacs, C
Kvale, PA
Reding, DJ
Weissfeld, JL
Yokochi, LA
O'Brien, B
Ragard, LR
Clapp, JD
Rathmell, JM
Riley, TL
Hsing, AW
Izmirlian, G
Pinsky, PF
Kramer, BS
Miller, AB
Gohagan, JK
Prorok, PC
AF Andriole, Gerald L.
Crawford, E. David
Grubb, Robert L., III
Buys, Saundra S.
Chia, David
Church, Timothy R.
Fouad, Mona N.
Isaacs, Claudine
Kvale, Paul A.
Reding, Douglas J.
Weissfeld, Joel L.
Yokochi, Lance A.
O'Brien, Barbara
Ragard, Lawrence R.
Clapp, Jonathan D.
Rathmell, Joshua M.
Riley, Thomas L.
Hsing, Ann W.
Izmirlian, Grant
Pinsky, Paul F.
Kramer, Barnett S.
Miller, Anthony B.
Gohagan, John K.
Prorok, Philip C.
CA PLCO Project Team
TI Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal,
and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of
Follow-up
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID COMORBIDITY
AB Background The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
Methods A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .68).
Conclusions After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
C1 [Izmirlian, Grant; Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Pinsky, Paul F.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Gohagan, John K.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[Andriole, Gerald L.; Grubb, Robert L., III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Crawford, E. David] Univ Colorado, Denver, CO 80202 USA.
[Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Chia, David] Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA.
[Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Fouad, Mona N.] Univ Alabama, Sch Med, Birmingham, AL USA.
[Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
[Kvale, Paul A.] Henry Ford Hlth Syst, Detroit, MI USA.
[Reding, Douglas J.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Weissfeld, Joel L.] Univ Pittsburgh, Med Ctr Canc Pavil, Pittsburgh, PA USA.
[Yokochi, Lance A.] Pacific Hlth Res Inst, Honolulu, HI USA.
[O'Brien, Barbara; Ragard, Lawrence R.] Westat Corp, Rockville, MD USA.
[Clapp, Jonathan D.; Rathmell, Joshua M.; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
[Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Prorok, PC (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Ste 3132, Bethesda, MD 20892 USA.
EM prorokp@mail.nih.gov
OI Church, Timothy R./0000-0003-3292-5035
FU National Cancer Institute and the National Institute of Diabetes and
Digestive and Kidney Diseases; GlaxoSmithKline; Human Genome Sciences,
Inc; National Cancer Institute at the National Institutes of Health
[N01-CN-25514, N01-CN-25522, N01-CN-25515, N01-CN-25512, N01-CN-25513,
N01-CN-25511, N01-CN-25524, N01-CN-25518, N01-CN-25516, N01-CN-75022,
N01-CN-25404, N01-CN-25476]
FX This work was supported by contracts from the National Cancer Institute
at the National Institutes of Health (N01-CN-25514 to E.D.C.;
N01-CN-25522 to C.I.; N01-CN-25515 to L.A.Y.; N01-CN-25512 to P.A.K.;
N01-CN-25513 to T.R.C.; N01-CN-25511 to J.L.W.; N01-CN-25524 to S.S.B.;
N01-CN-25518 to D.J.R.; N01-CN-25516 to G.L.A. and R.L.G.; N01-CN-75022
to M.N.F.; N01-CN-25404 to D.C.; and N01-CN-25476 to B.O'B and L.R.R.).;
G. L. Andriole serves as a Consultant/Advisor for Amgen, Augmenix,
Bayer, Cambridge Endo, Caris, France Foundation, GenProbe,
GlaxoSmithKline, Myriad Genetics, Steba Biotech, and Ortho Clinical
Diagnostics. He serves as Medical Director of Envisioneering Medical and
Viking Medical. He is the recipient of grant support from the National
Cancer Institute and the National Institute of Diabetes and Digestive
and Kidney Diseases. R. L. Grubb conducts research sponsored by
GlaxoSmithKline. J. D. Clapp has a financial interest in Human Genome
Sciences, Inc, which conducts research and development in the treatment
of hepatitis, lupus, and cancer. The Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial is a federally funded registered clinical
trial (ClinicalTrials.gov identifier NCT00002540). We thank the study
participants for their contributions in making this study possible. The
authors are solely responsible for the study design, data collection,
analysis and interpretation of the data, writing the article, and
decision to submit the article for publication.
NR 22
TC 425
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U1 5
U2 51
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN
PY 2012
VL 104
IS 2
BP 125
EP 132
DI 10.1093/jnci/djr500
PG 8
WC Oncology
SC Oncology
GA 879QF
UT WOS:000299346200008
PM 22228146
ER
PT J
AU Sitas, F
Egger, S
Urban, MI
Taylor, PR
Abnet, CC
Boffetta, P
O'Connell, DL
Whiteman, DC
Brennan, P
Malekzadeh, R
Pawlita, M
Dawsey, SM
Waterboer, T
AF Sitas, Freddy
Egger, Sam
Urban, Margaret I.
Taylor, Philip R.
Abnet, Christian C.
Boffetta, Paolo
O'Connell, Dianne L.
Whiteman, David C.
Brennan, Paul
Malekzadeh, Reza
Pawlita, Michael
Dawsey, Sanford M.
Waterboer, Tim
CA InterSCOPE Collaboration
TI InterSCOPE Study: Associations Between Esophageal Squamous Cell
Carcinoma and Human Papillomavirus Serological Markers
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HIGH-RISK AREA; GLUTATHIONE-S-TRANSFERASE; UPPER AERODIGESTIVE TRACT;
INVASIVE CERVICAL-CANCER; GASTRIC CANCERS; TYPE-16 INFECTION;
ALCOHOL-USE; VIRUS HPV; TOBACCO; CHINA
AB Background The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing background risks of esophageal cancer.
Methods We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided.
Results We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036).
Conclusions We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers.
C1 [Sitas, Freddy; Egger, Sam; O'Connell, Dianne L.] NSW Canc Council, Canc Epidemiol Res Unit, Sydney, NSW, Australia.
German Canc Res Ctr, Genome Modificat & Carcinogenesis Div, Infect & Canc Program, D-6900 Heidelberg, Germany.
[Taylor, Philip R.; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
Natl Hlth Lab Serv, NHLS MRC Canc Epidemiol Res Grp, Johannesburg, South Africa.
[Urban, Margaret I.] Univ Witwatersrand, Johannesburg, South Africa.
Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Whiteman, David C.] Queensland Inst Med Res, Populat Hlth Dept, Brisbane, Qld 4006, Australia.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran.
RP Sitas, F (reprint author), NSW Canc Council, Canc Epidemiol Res Unit, POB 572, Kings Cross, NSW 1340, Australia.
EM freddys@nswcc.org.au
RI Abnet, Christian/C-4111-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010;
Whiteman, David/P-2728-2014; Waterboer, Tim/G-1252-2010; Pawlita,
Labor/C-9720-2011; Curado, Maria Paula/M-6200-2013; Zaridze,
David/K-5605-2013; hayward, nicholas/C-1367-2015
OI Pawlita, Michael/0000-0002-4720-8306; Abnet,
Christian/0000-0002-3008-7843; Whiteman, David/0000-0003-2563-9559;
Curado, Maria Paula/0000-0001-8172-2483; mates,
dana/0000-0002-6219-9807; Malekzadeh, Reza/0000-0003-1043-3814; Sitas,
Freddy/0000-0001-9679-1481; hayward, nicholas/0000-0003-4760-1033
FU US National Cancer Institute; German Cancer Research Center; Cancer
Council New South Wales, Australia; Deutsche Krebshilfe; European
Commission [IC18-CT97-0222]
FX The InterSCOPE collaboration was partially funded by the intramural
research programs of the US National Cancer Institute; the German Cancer
Research Center; and Cancer Council New South Wales, Australia; and by
grants from the Deutsche Krebshilfe. Institutions who funded the field
work of the original studies were Brazilian Multicentric Case-Control
Study: European Commission (grant no IC18-CT97-0222); Central and
Eastern European Case-Control Study: World Cancer Research Fund,
European Commission (Contract No. IC15-CT98-0332); The Golestan
Case-Control Study: Digestive Disease Research Center, Tehran University
of Medical Sciences (Grant Number 82-603); The Australian Cancer Study:
National Health and Medical Research Council (Program Grant No. 199600)
(Australia); Johannesburg Cancer Case-Control Study: South African
National Health Laboratory Service and Medical Research Council;
University of the Witwatersrand; Cancer Research UK; Shanxi Case-Control
Study: the US National Cancer Institute (Contract NO2-SC-66211).
NR 62
TC 31
Z9 32
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN
PY 2012
VL 104
IS 2
BP 147
EP 158
DI 10.1093/jnci/djr499
PG 12
WC Oncology
SC Oncology
GA 879QF
UT WOS:000299346200010
PM 22228147
ER
PT J
AU Safaeian, M
Wacholder, S
Hildesheim, A
AF Safaeian, Mahboobeh
Wacholder, Sholom
Hildesheim, Allan
TI Re: Epidemiological Study of Anti-HPV16/18 Seropositivity and Subsequent
Risk of HPV16 and-18 Infections Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID HUMAN-PAPILLOMAVIRUS TYPE; COSTA-RICA; SEROPREVALENCE; WOMEN
C1 [Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, Rockville, MD 20852 USA.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, 6120 Execut Blvd,Ste 550, Rockville, MD 20852 USA.
EM safaeianm@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
NR 4
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN
PY 2012
VL 104
IS 2
BP 163
EP 164
DI 10.1093/jnci/djr519
PG 2
WC Oncology
SC Oncology
GA 879QF
UT WOS:000299346200013
ER
PT J
AU Magadan, JG
Bonifacino, JS
AF Magadan, Javier G.
Bonifacino, Juan S.
TI Transmembrane Domain Determinants of CD4 Downregulation by HIV-1 Vpu
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS TYPE-1 NEF; CHIMERIC ENVELOPE GLYCOPROTEINS; PROTEIN-U VPU;
ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; 3-DIMENSIONAL STRUCTURE;
MEMBRANE INTERFACES; RETRO-TRANSLOCATION; INDUCED DEGRADATION; SURFACE
EXPRESSION
AB The transmembrane domains (TMDs) of integral membrane proteins do not merely function as membrane anchors but play active roles in many important biological processes. The downregulation of the CD4 coreceptor by the Vpu protein of HIV-1 is a prime example of a process that is dependent on specific properties of TMDs. Here we report the identification of Trp22 in the Vpu TMD and Gly415 in the CD4 TMD as critical determinants of Vpu-induced targeting of CD4 to endoplasmic reticulum (ER)-associated degradation (ERAD). The two residues participate in different aspects of ERAD targeting. Vpu Trp22 is required to prevent assembly of Vpu into an inactive, oligomeric form and to promote CD4 polyubiquitination and subsequent recruitment of the VCP-UFD1L-NPL4 dislocase complex. In the presence of a Vpu Trp22 mutant, CD4 remains integrally associated with the ER membrane, suggesting that dislocation from the ER into the cytosol is impaired. CD4 Gly415, on the other hand, contributes to CD4-Vpu interactions. We also identify two residues, Val20 and Ser23, in the Vpu TMD that mediate retention of Vpu and, by extension, CD4 in the ER. These findings highlight the exploitation of several TMD-mediated mechanisms by HIV-1 Vpu in order to downregulate CD4 and thus promote viral pathogenesis.
C1 [Magadan, Javier G.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU NIH; NICHD; Pew Charitable Trusts
FX This work was supported by the NIH Intramural AIDS Targeted Antiviral
Program (IATAP) and the Intramural Program of the NICHD. J.G.M. is the
recipient of a fellowship from The Pew Charitable Trusts.
NR 87
TC 30
Z9 33
U1 4
U2 6
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 JAN
PY 2012
VL 86
IS 2
BP 757
EP 772
DI 10.1128/JVI.05933-11
PG 16
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600011
PM 22090097
ER
PT J
AU Thai, KTD
Henn, MR
Zody, MC
Tricou, V
Nguyet, NM
Charlebois, P
Lennon, NJ
Green, L
de Vries, PJ
Hien, TT
Farrar, J
van Doorn, HR
de Jong, MD
Birren, BW
Holmes, EC
Simmons, CP
AF Thai, Khoa T. D.
Henn, Matthew R.
Zody, Michael C.
Tricou, Vianney
Nguyen Minh Nguyet
Charlebois, Patrick
Lennon, Niall J.
Green, Lisa
de Vries, Peter J.
Tran Tinh Hien
Farrar, Jeremy
van Doorn, H. Rogier
de Jong, Menno D.
Birren, Bruce W.
Holmes, Edward C.
Simmons, Cameron P.
TI High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus
Serotype 1 Infection Identifies Mixed Infections
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EVOLUTIONARY GENETICS; MAXIMUM-LIKELIHOOD; FRENCH-POLYNESIA; TYPE-3
VIRUS; IN-VIVO; RNA; EMERGENCE; HOST; RECOMBINATION; TRANSMISSION
AB Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia.
C1 [Thai, Khoa T. D.; Tricou, Vianney; Nguyen Minh Nguyet; Tran Tinh Hien; Farrar, Jeremy; van Doorn, H. Rogier; Simmons, Cameron P.] Hosp Trop Dis, Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam.
[Farrar, Jeremy; van Doorn, H. Rogier; Simmons, Cameron P.] Univ Oxford, Nuffield Dept Clin Med, Ctr Clin Vaccinol & Trop Med, Ctr Trop Med, Oxford, England.
[Thai, Khoa T. D.; de Vries, Peter J.] Univ Amsterdam, Acad Med Ctr, Trop Med & AIDS, Div Infect Dis, NL-1105 AZ Amsterdam, Netherlands.
[Thai, Khoa T. D.; de Vries, Peter J.; de Jong, Menno D.] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Inflammat Res, NL-1105 AZ Amsterdam, Netherlands.
[de Jong, Menno D.] Univ Amsterdam, Acad Med Ctr, Div Clin Virol, NL-1105 AZ Amsterdam, Netherlands.
[Henn, Matthew R.; Zody, Michael C.; Charlebois, Patrick; Lennon, Niall J.; Green, Lisa; Birren, Bruce W.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Thai, KTD (reprint author), Hosp Trop Dis, Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam.
EM khoat@oucru.org
OI van Doorn, H Rogier/0000-0002-9807-1821; Simmons, Cameron
P./0000-0002-9039-7392; Tricou, Vianney/0000-0002-5465-8647; Farrar,
Jeremy/0000-0002-2700-623X; Holmes, Edward/0000-0001-9596-3552
FU Wellcome Trust; National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services
[HHSN272200900006C, HHSN272200900018C]; Netherlands Organization for
Scientific Research (NWO) [017.004.074]
FX This study was funded by the Wellcome Trust (C. P. S.) and in part with
U.S. Federal funds from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services, under contract no. HHSN272200900006C (B. W. B.) and
HHSN272200900018C (B. W. B.). Khoa T. D. Thai is supported by a "Mosaic"
fellowship from the Netherlands Organization for Scientific Research
(NWO) (grant 017.004.074).
NR 39
TC 37
Z9 37
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN
PY 2012
VL 86
IS 2
BP 835
EP 843
DI 10.1128/JVI.05985-11
PG 9
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600017
PM 22090119
ER
PT J
AU Allison, AB
Harbison, CE
Pagan, I
Stucker, KM
Kaelber, JT
Brown, JD
Ruder, MG
Keel, MK
Dubovi, EJ
Holmes, EC
Parrish, CR
AF Allison, Andrew B.
Harbison, Carole E.
Pagan, Israel
Stucker, Karla M.
Kaelber, Jason T.
Brown, Justin D.
Ruder, Mark G.
Keel, M. Kevin
Dubovi, Edward J.
Holmes, Edward C.
Parrish, Colin R.
TI Role of Multiple Hosts in the Cross-Species Transmission and Emergence
of a Pandemic Parvovirus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FELINE PANLEUKOPENIA VIRUS; MINK ENTERITIS VIRUS; CANINE PARVOVIRUS;
TRANSFERRIN RECEPTORS; CAPSID STRUCTURE; IN-VIVO; RANGE; EVOLUTION;
BINDING; CELLS
AB Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence.
C1 [Allison, Andrew B.; Harbison, Carole E.; Stucker, Karla M.; Kaelber, Jason T.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
[Allison, Andrew B.; Brown, Justin D.; Ruder, Mark G.; Keel, M. Kevin] Univ Georgia, Coll Vet Med, SE Cooperat Wildlife Dis Study, Athens, GA USA.
[Pagan, Israel; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Kaelber, Jason T.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Dubovi, Edward J.] Cornell Univ, Coll Vet Med, Dept Populat Med, Ithaca, NY 14853 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
EM crp3@cornell.edu
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Kaelber, Jason/0000-0001-9426-1030;
Allison, Andrew B./0000-0003-0971-1215; Holmes,
Edward/0000-0001-9596-3552
FU Southeastern Cooperative Wildlife Disease Study (SCWDS); Marie Curie
fellowship [PIOF-GA-2009-236470]; NIH [GM080533-05, AI028385, AI092571]
FX A.B.A., J.D.B., M. G. R., and M. K. K. were supported by funds obtained
through sponsorship by the fish and wildlife agencies of the member
states of the Southeastern Cooperative Wildlife Disease Study (SCWDS).
A. B. A. thanks Jeremiah Saliki at the University of Georgia for
graciously allowing the use of his laboratory space. I. P. was supported
by Marie Curie fellowship PIOF-GA-2009-236470. This work was also
supported by NIH grants GM080533-05 (to E. C. H. and C. R. P.),
AI028385, and AI092571 (to C.R.P.).
NR 35
TC 34
Z9 34
U1 1
U2 32
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 JAN
PY 2012
VL 86
IS 2
BP 865
EP 872
DI 10.1128/JVI.06187-11
PG 8
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600020
PM 22072763
ER
PT J
AU Frieman, M
Yount, B
Agnihothram, S
Page, C
Donaldson, E
Roberts, A
Vogel, L
Woodruff, B
Scorpio, D
Subbarao, K
Baric, RS
AF Frieman, Matthew
Yount, Boyd
Agnihothram, Sudhakar
Page, Carly
Donaldson, Eric
Roberts, Anjeanette
Vogel, Leatrice
Woodruff, Becky
Scorpio, Diana
Subbarao, Kanta
Baric, Ralph S.
TI Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus
Pathogenesis and Virulence in Young and Aged Mouse Models of Human
Disease
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PAPAIN-LIKE PROTEASE; ANGIOTENSIN-CONVERTING ENZYME-2; SARS-CORONAVIRUS;
VIRUS-INFECTION; HEPATITIS-VIRUS; SPIKE PROTEIN; I INTERFERON; FEVER
VIRUS; BALB/C MICE; RECEPTOR
AB SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.
C1 [Frieman, Matthew; Page, Carly] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Yount, Boyd; Agnihothram, Sudhakar; Donaldson, Eric; Woodruff, Becky; Baric, Ralph S.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Roberts, Anjeanette; Vogel, Leatrice; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Scorpio, Diana] Johns Hopkins Univ, Dept Mol & Comparat Pathol, Baltimore, MD USA.
RP Frieman, M (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM mfrieman@som.umaryland.edu
RI Scorpio, Diana/C-4839-2012
FU NIH [AI075297, F32 AI066542]; NIAID, NIH
FX This work was generously supported by NIH grant AI075297 to R. S. Baric,
and M. Frieman was supported by NIH training grant F32 AI066542. This
research was supported in part by the Intramural Research Program of the
NIAID, NIH.
NR 75
TC 23
Z9 25
U1 0
U2 5
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 JAN
PY 2012
VL 86
IS 2
BP 884
EP 897
DI 10.1128/JVI.05957-11
PG 14
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600022
PM 22072787
ER
PT J
AU Kong, R
Li, H
Bibollet-Ruche, F
Decker, JM
Zheng, NN
Gottlieb, GS
Kiviat, NB
Sow, PS
Georgiev, I
Hahn, BH
Kwong, PD
Robinson, JE
Shaw, GM
AF Kong, Rui
Li, Hui
Bibollet-Ruche, Frederic
Decker, Julie M.
Zheng, Natalie N.
Gottlieb, Geoffrey S.
Kiviat, Nancy B.
Sow, Papa Salif
Georgiev, Ivelin
Hahn, Beatrice H.
Kwong, Peter D.
Robinson, James E.
Shaw, George M.
TI Broad and Potent Neutralizing Antibody Responses Elicited in Natural
HIV-2 Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RHESUS MONOCLONAL-ANTIBODIES; BLOOD
MONONUCLEAR-CELLS; FUSION INHIBITOR T-20; HIV-2-INFECTED INDIVIDUALS;
MEDIATED NEUTRALIZATION; V3-SPECIFIC ANTIBODIES; ENVELOPE GLYCOPROTEINS;
WEST-AFRICA; VIRAL LOAD
AB Compared with human immunodeficiency virus type 1 (HIV-1), little is known about the susceptibility of HIV-2 to antibody neutralization. We characterized the potency and breadth of neutralizing antibody (NAb) responses in 64 subjects chronically infected with HIV-2 against three primary HIV-2 strains: HIV-2(7312A), HIV-2(ST), and HIV-2(UC1). Surprisingly, we observed in a single-cycle JC53bl-13/TZM-bl virus entry assay median reciprocal 50% inhibitory concentration (IC(50)) NAb titers of 1.7 x 10(5), 2.8 x 10(4), and 3.3 x 10(4), respectively. A subset of 5 patient plasma samples tested against a larger panel of 17 HIV-2 strains where the extracellular gp160 domain was substituted into the HIV-2(7312A) proviral backbone showed potent neutralization of all but 4 viruses. The specificity of antibody neutralization was confirmed using IgG purified from patient plasma, HIV-2 Envs cloned by single-genome amplification, viruses grown in human CD4(+) T cells and tested for neutralization sensitivity on human CD4(+) T target cells, and, as negative controls, env-minus viruses pseudotyped with HIV-1, vesicular stomatitis virus, or murine leukemia virus Env glycoproteins. Human monoclonal antibodies (MAbs) specific for HIV-2 V3 (6.10F), V4 (1.7A), CD4 binding site (CD4bs; 6.10B), CD4 induced (CD4i; 1.4H), and membrane-proximal external region (MPER; 4E10) epitopes potently neutralized the majority of 32 HIV-2 strains bearing Envs from 13 subjects. Patient antibodies competed with V3, V4, and CD4bs MAbs for binding to monomeric HIV-2 gp120 at titers that correlated significantly with NAb titers. HIV-2 MPER antibodies did not contribute to neutralization breadth or potency. These findings indicate that HIV-2 Env is highly immunogenic in natural infection, that high-titer broadly neutralizing antibodies are commonly elicited, and that unlike HIV-1, native HIV-2 Env trimers expose multiple broadly cross-reactive epitopes readily accessible to NAbs.
C1 [Li, Hui; Bibollet-Ruche, Frederic; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Sch Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kong, Rui; Decker, Julie M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Kong, Rui; Decker, Julie M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Zheng, Natalie N.; Gottlieb, Geoffrey S.; Kiviat, Nancy B.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Zheng, Natalie N.; Gottlieb, Geoffrey S.; Kiviat, Nancy B.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Sow, Papa Salif] Univ Cheikh Anta Diop Dakar, Ctr Hosp Univ Fann, Clin Malad Infect Ibrahima DIOP Mar, Dakar, Senegal.
[Georgiev, Ivelin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA.
RP Shaw, GM (reprint author), Univ Penn, Sch Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM shawg@upenn.edu
FU NIH [AI67854, AI88564, AI87383]
FX This work was supported by grants from the NIH (AI67854, AI88564, and
AI87383).
NR 66
TC 29
Z9 29
U1 0
U2 5
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 JAN
PY 2012
VL 86
IS 2
BP 947
EP 960
DI 10.1128/JVI.06155-11
PG 14
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600027
PM 22031948
ER
PT J
AU Veeranna, RP
Haque, M
Davis, DA
Yang, M
Yarchoan, R
AF Veeranna, Ravindra P.
Haque, Muzammel
Davis, David A.
Yang, Min
Yarchoan, Robert
TI Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear
Antigen Induction by Hypoxia and Hypoxia-Inducible Factors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LYMPHOMA CELL-LINE; EPSTEIN-BARR-VIRUS; PAS DOMAIN PROTEIN-1;
ENDOTHELIAL-CELLS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 DNA; LYTIC
REPLICATION; BINDING PROTEIN; GENE-EXPRESSION; TRANSCRIPTION
AB Hypoxia and hypoxia-inducible factors (HIFs) play an important role in the Kaposi's sarcoma-associated herpesvirus (KSHV) life cycle. In particular, hypoxia can activate lytic replication of KSHV and specific lytic genes, including the replication and transcription activator (RTA), while KSHV infection in turn can increase the levels and activity of HIFs. In the present study, we show that hypoxia increases the levels of mRNAs encoding KSHV latency-associated nuclear antigen (LANA) in primary effusion lymphoma (PEL) cell lines and also increases the levels of LANA protein. Luciferase reporter assays in Hep3B cells revealed a moderate activation of the LANA promoter region by hypoxia as well as by cotransfection with degradation-resistant HIF-1 alpha or HIF-2 alpha expression plasmids. Computer analysis of a 1.2-kb sequence upstream of the LANA translational start site identified six potential hypoxia-responsive elements (HRE). Sequential deletion studies revealed that much of this activity was mediated by one of these HREs (HRE 4R) oriented in the 3' to 5' direction and located between the constitutive (LTc) and RTA-inducible (LTi) mRNA start sites. Site-directed mutation of this HRE substantially reduced the response to both HIF-1 alpha and HIF-2 alpha in a luciferase reporter assay. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated binding of both HIF-1 alpha and HIF-2 alpha to this region. Also, HIF-1 alpha was found to associate with RTA, and HIFs enhanced the activation of LTi by RTA. These results provide evidence that hypoxia and HIFs upregulate both latent and lytic KSHV replication and play a central role in the life cycle of this virus.
C1 [Veeranna, Ravindra P.; Haque, Muzammel; Davis, David A.; Yang, Min; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM yarchoan@helix.nih.gov
OI Ravindra, P V/0000-0003-4228-1843
FU NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute.
NR 55
TC 11
Z9 11
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN
PY 2012
VL 86
IS 2
BP 1097
EP 1108
DI 10.1128/JVI.05167-11
PG 12
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600041
PM 22090111
ER
PT J
AU Klatt, NR
Canary, LA
Vanderford, TH
Vinton, CL
Engram, JC
Dunham, RM
Cronise, HE
Swerczek, JM
Lafont, BAP
Picker, LJ
Silvestri, G
Brenchley, JM
AF Klatt, Nichole R.
Canary, Lauren A.
Vanderford, Thomas H.
Vinton, Carol L.
Engram, Jessica C.
Dunham, Richard M.
Cronise, Heather E.
Swerczek, Joanna M.
Lafont, Bernard A. P.
Picker, Louis J.
Silvestri, Guido
Brenchley, Jason M.
TI Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail
Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PIG-TAILED MACAQUES; CD4(+) T-CELLS; ACUTE SIV INFECTION;
MACACA-NEMESTRINA; IMMUNE ACTIVATION; HIV-1 INFECTION; IN-VIVO; AFRICAN
INDIVIDUALS; TYPE-1 INFECTION; MOLECULAR CLONES
AB Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.
C1 [Klatt, Nichole R.; Canary, Lauren A.; Vinton, Carol L.; Lafont, Bernard A. P.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Klatt, Nichole R.; Canary, Lauren A.; Vinton, Carol L.; Lafont, Bernard A. P.; Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA.
[Vanderford, Thomas H.; Engram, Jessica C.; Dunham, Richard M.; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Cronise, Heather E.; Swerczek, Joanna M.] NIAID, Comparat Med Branch, NIH, Poolesville, MD USA.
[Picker, Louis J.] Oregon Hlth & Sci Univ, VGTI, Dept Mol Microbiol, Beaverton, OR USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM jbrenchl@niaid.nih.gov
RI Dunham, Richard/B-2012-2009; Lafont, Bernard/B-7236-2014
OI Dunham, Richard/0000-0003-4542-2330;
FU National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of Health; NIH [R01-AI90797, AI054292]; ONPRC [RR00163]
FX These studies were supported by the intramural program of the National
Institute of Allergy and Infectious Diseases, U.S. National Institutes
of Health, and in part by NIH grants R01-AI90797 to G. Silvestri and
AI054292 to L. Picker as well as ONPRC Core grant RR00163.
NR 61
TC 22
Z9 25
U1 1
U2 6
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 JAN
PY 2012
VL 86
IS 2
BP 1203
EP 1213
DI 10.1128/JVI.06033-11
PG 11
WC Virology
SC Virology
GA 870MW
UT WOS:000298674600050
PM 22090099
ER
PT J
AU Schiefelbein, EL
Mirchandani, GG
George, GC
Becker, EA
Castrucci, BC
Hoelscher, DM
AF Schiefelbein, Emily L.
Mirchandani, Gita G.
George, Goldy C.
Becker, Emilie A.
Castrucci, Brian C.
Hoelscher, Deanna M.
TI Association Between Depressed Mood and Perceived Weight in Middle and
High School Age Students: Texas 2004-2005
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Adolescent; Body weight; Weight perception; Overweight; Obesity;
Depression
ID BODY-MASS INDEX; MENTAL-HEALTH OUTCOMES; ADOLESCENT GIRLS; RISK-FACTORS;
CLINICAL-IMPLICATIONS; GENDER-DIFFERENCES; YOUNG ADOLESCENTS;
PHYSICAL-ACTIVITY; OVERWEIGHT STATUS; UNITED-STATES
AB Research exploring the relationship between weight perception and depressed mood among adolescents is limited in the United States. The purpose of this study is to examine the association of perceived versus actual body weight and depressed mood in a representative sample of 8th and 11th grade public school students in Texas. Using data from the 2004-2005 School Physical Activity and Nutrition (SPAN) study, logistic regression analyses were conducted to assess the association of weight perception with depressed mood. Healthy weight students who perceived themselves to be a healthy weight were the reference group for all analyses. A high prevalence of misperception of body weight was observed. Overweight and obese 8th grade girls and boys who perceived themselves to be overweight had increased odds of depressed mood [Girls: OR 1.70 (95% CI: 1.07-2.69), Boys: OR 2.05 (95% CI: 1.16-3.62)]. Healthy weight 8th grade girls who perceived themselves to be overweight had 2.5 times greater odds of depressed mood (OR 2.63, 95% CI: 1.54-4.50). Healthy weight boys who perceived themselves to be underweight had more than twice the odds (OR 2.18, 95% CI: 1.23-3.89) of depressed mood. No weight category was significantly associated with depressed mood in boys or girls in 11th grade. The present study suggests that weight misperceptions are associated with depressed mood in young adolescents. Education about healthy body size is necessary to correct the common weight misperceptions observed. The high prevalence rates of depressed mood suggest a greater need for research into understanding factors that may contribute to depressed mood in adolescents.
C1 [Schiefelbein, Emily L.] Ctr Dis Control & Prevent, CDC CSTE Appl Epidemiol Fellowship Program, Div Family & Community Hlth Serv, Council State & Terr Epidemiologists,Texas Dept S, Austin, TX 78714 USA.
[George, Goldy C.] NCI, Bethesda, MD 20892 USA.
[George, Goldy C.] Univ Texas Sch Publ Hlth, Michael & Susan Dell Ctr Adv Hlth Living, Houston, TX USA.
[Becker, Emilie A.] Texas Dept State Hlth Serv, Div Mental Hlth & Subst Abuse, Austin, TX USA.
[Castrucci, Brian C.] Georgia Dept Publ Hlth, Maternal & Child Hlth Program, Austin, TX USA.
[Hoelscher, Deanna M.] Univ Texas Sch Publ Hlth Austin, Michael & Susan Dell Ctr Adv Hlth Living, Austin, TX USA.
RP Schiefelbein, EL (reprint author), Ctr Dis Control & Prevent, CDC CSTE Appl Epidemiol Fellowship Program, Div Family & Community Hlth Serv, Council State & Terr Epidemiologists,Texas Dept S, MC 1922,POB 149347, Austin, TX 78714 USA.
EM Emily.schiefelbein@gmail.com; gita.mirchandani@dshs.state.tx.us;
goldyjg@yahoo.com; emilie.becker@dshs.state.tx.us;
brian.castrucci@gmail.com; deanna.m.hoelscher@uth.tmc.edu
FU NCHM CDC HHS [5U38HM000414]
NR 49
TC 5
Z9 5
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD JAN
PY 2012
VL 16
IS 1
BP 169
EP 176
DI 10.1007/s10995-010-0733-1
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 875AL
UT WOS:000299001100019
PM 21165762
ER
PT J
AU Pena, L
Franks, J
Chapman, KA
Gropman, A
Mew, NA
Chakrapani, A
Island, E
MacLeod, E
Matern, D
Smith, B
Stagni, K
Sutton, VR
Ueda, K
Urv, T
Venditti, C
Enns, GM
Summar, ML
AF Pena, Loren
Franks, Jill
Chapman, Kimberly A.
Gropman, Andrea
Mew, Nicholas Ah
Chakrapani, Anupam
Island, Eddie
MacLeod, Erin
Matern, Dietrich
Smith, Brittany
Stagni, Kathy
Sutton, V. Reid
Ueda, Keiko
Urv, Tiina
Venditti, Charles
Enns, Gregory M.
Summar, Marshall L.
TI Natural history of propionic acidemia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Propionic acidemia; Organic acidemia; Pancreatitis; Cardiomyopathy; Long
QT interval; Long-term complications
ID METHYLMALONIC ACIDURIA; ACUTE-PANCREATITIS; IDIOPATHIC HYPERGLYCINEMIA;
KETOTIC-HYPERGLYCINEMIA; METABOLISM; DISORDERS; CARDIOMYOPATHY;
CARBOXYLASE; DEFICIENCY; MANAGEMENT
AB Propionic acidemia is an organic acidemia that can lead to metabolic acidosis, coma and death, if not treated appropriately in the acute setting. Recent advancements in treatment have allowed patients with propionic acidemia to live beyond the neonatal period and acute presentation. The natural history of the disease is just beginning to be elucidated as individuals reach older ages. Recent studies have identified the genomic mutations in the genes PCCA and PCCB. However, as of yet no clear genotype-phenotype correlations are known. As patients age, the natural progression of propionic acidemia illuminates intellectual difficulties, increased risk for neurological complications, including stroke-like episodes, cardiac complications, and gastrointestinal difficulties, as well as a number of other complications. This article reviews the available literature for the natural history of propionic acidemia.
C1 [Pena, Loren] Univ Illinois, Dept Pediat, Div Genet, Coll Med Chicago, Chicago, IL 60612 USA.
[Franks, Jill; Smith, Brittany] Propion Acidemia Fdn, Highland Pk, IL USA.
[Chapman, Kimberly A.; Gropman, Andrea; Mew, Nicholas Ah; MacLeod, Erin; Summar, Marshall L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Chakrapani, Anupam] Birmingham Childrens Hosp, Birmingham, W Midlands, England.
[Island, Eddie] Georgetown Univ, Transplant Program, Washington, DC USA.
[Matern, Dietrich] Mayo Clin, Rochester, MN USA.
[Stagni, Kathy] Organ Acidemia Assoc, Pinole, CA USA.
[Sutton, V. Reid] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Sutton, V. Reid] Texas Childrens Hosp, Houston, TX 77030 USA.
[Ueda, Keiko] Tufts Med Ctr, Boston, MA USA.
[Urv, Tiina; Venditti, Charles] NIH, Bethesda, MD 20892 USA.
[Enns, Gregory M.] Stanford Univ, Palo Alto, CA 94304 USA.
RP Pena, L (reprint author), Univ Illinois, Dept Pediat, Div Genet, Coll Med Chicago, 840 S Wood St,12th Floor,MC 856, Chicago, IL 60612 USA.
EM lpena@uic.edu
NR 60
TC 27
Z9 27
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2012
VL 105
IS 1
BP 5
EP 9
DI 10.1016/j.ymgme.2011.09.022
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 879WO
UT WOS:000299363800003
PM 21986446
ER
PT J
AU Schreiber, J
Chapman, KA
Summar, ML
Mew, NA
Sutton, VR
MacLeod, E
Stagni, K
Ueda, K
Franks, J
Island, E
Matern, D
Pena, L
Smith, B
Urv, T
Venditti, C
Chakarapani, A
Gropman, AL
AF Schreiber, John
Chapman, Kimberly A.
Summar, Marshall L.
Mew, Nicholas Ah
Sutton, V. Reid
MacLeod, Erin
Stagni, Kathy
Ueda, Keiko
Franks, Jill
Island, Eddie
Matern, Dietrich
Pena, Loren
Smith, Brittany
Urv, Tiina
Venditti, Charles
Chakarapani, Anupam
Gropman, Andrea L.
TI Neurologic considerations in propionic acidemia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Propionic acidemia; Neurological; Seizure; Neuroimaging; Spectroscopy;
Inborn error of metabolism
ID IN-VITRO PHOSPHORYLATION; RAT CEREBRAL-CORTEX; BRAIN; ONSET;
NEUROPATHOLOGY; SPECTROSCOPY; METABOLISM; DISORDERS; ACIDS
AB Propionic acidemia (PA) is an organic acidemia which has a broad range of neurological complications, including developmental delay, intellectual disability, structural abnormalities, metabolic stroke-like episodes, seizures, optic neuropathy, and cranial nerve abnormalities. As the PA consensus conference hosted by Children's National Medical Center progressed from January 28 to 30, 2011, it became evident that neurological complications were common and a major component of morbidity, but the role of imaging and the basis for brain pathophysiology were unclear. This paper reviews the hypothesized pathophysiology, presentation and uses the best available evidence to suggest programs for treatment, imaging, and monitoring the neurological complications of PA,
C1 [Schreiber, John; Gropman, Andrea L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Chapman, Kimberly A.; Summar, Marshall L.; Mew, Nicholas Ah; MacLeod, Erin] Childrens Natl Med Ctr, Sect Genet & Metab, Washington, DC 20010 USA.
[Sutton, V. Reid] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Sutton, V. Reid] Texas Childrens Hosp, Houston, TX 77030 USA.
[Stagni, Kathy] Organ Acidemia Assoc, Pinole, CA USA.
[Ueda, Keiko] Tufts Med Ctr, Boston, MA USA.
[Franks, Jill; Smith, Brittany] Propion Acidemia Fdn, Highland, IL USA.
[Island, Eddie] Georgetown Univ, Transplant Program, Washington, DC USA.
[Matern, Dietrich] Mayo Clin, Rochester, MN USA.
[Pena, Loren] Univ Illinois, Coll Med Chicago, Chicago, IL USA.
[Urv, Tiina; Venditti, Charles] NIH, Bethesda, MD 20892 USA.
[Chakarapani, Anupam] Birmingham Childrens Hosp, Birmingham, W Midlands, England.
RP Gropman, AL (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM agropman@childrensnational.org
NR 40
TC 18
Z9 20
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2012
VL 105
IS 1
BP 10
EP 15
DI 10.1016/j.ymgme.2011.10.003
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 879WO
UT WOS:000299363800004
PM 22078457
ER
PT J
AU Chapman, KA
Gropman, A
MacLeod, E
Stagni, K
Summar, ML
Ueda, K
Mew, NA
Franks, J
Island, E
Matern, D
Pena, L
Smith, B
Sutton, VR
Urv, T
Venditti, C
Chakrapani, A
AF Chapman, Kimberly A.
Gropman, Andrea
MacLeod, Erin
Stagni, Kathy
Summar, Marshall L.
Ueda, Keiko
Mew, Nicholas Ah
Franks, Jill
Island, Eddie
Matern, Dietrich
Pena, Loren
Smith, Brittany
Sutton, V. Reid
Urv, Tiina
Venditti, Charles
Chakrapani, Anupam
TI Acute management of propionic acidemia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Propionic acidemia; Inborn error of metabolism; Organic acidemia;
Treatment; Acute management
ID EMERGENCY CARDIOVASCULAR CARE; RESTING ENERGY-EXPENDITURE;
SYRUP-URINE-DISEASE; METHYLMALONIC ACIDEMIA; L-CARNITINE; INBORN-ERRORS;
CARDIOPULMONARY-RESUSCITATION; PARENTERAL-NUTRITION; METABOLIC DISEASES;
SAUDI-ARABIA
AB Propionic acidemia or aciduria is an intoxication-type disorder of organic metabolism. Patients deteriorate in times of increased metabolic demand and subsequent catabolism. Metabolic decompensation can manifest with lethargy, vomiting, coma and death if not appropriately treated. On January 28-30,2011 in Washington, D.C., Children's National Medical Center hosted a group of clinicians, scientists and parental group representatives to design recommendations for acute management of individuals with propionic acidemia. Although many of the recommendations are geared toward the previously undiagnosed neonate, the recommendations for a severely metabolically decompensated individual are applicable to any known patient as well. Initial management is critical for prevention of morbidity and mortality. The following manuscript provides recommendations for initial treatment and evaluation, a discussion of issues concerning transport to a metabolic center (if patient presents to a non-metabolic center), acceleration of management and preparation for discharge.
C1 [Chapman, Kimberly A.; Gropman, Andrea; MacLeod, Erin; Summar, Marshall L.; Mew, Nicholas Ah] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Stagni, Kathy] Organ Acidemia Assoc, Pinole, CA USA.
[Ueda, Keiko] Tufts Med Ctr, Boston, MA USA.
[Franks, Jill; Smith, Brittany] Propion Acidemia Fdn, Highland Pk, IL USA.
[Island, Eddie] Georgetown Univ, Transplant Program, Washington, DC USA.
[Matern, Dietrich] Mayo Clin, Rochester, MN USA.
[Pena, Loren] Univ Illinois, Coll Med Chicago, Chicago, IL USA.
[Sutton, V. Reid] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Sutton, V. Reid] Texas Childrens Hosp, Houston, TX 77030 USA.
[Urv, Tiina; Venditti, Charles] NIH, Bethesda, MD 20892 USA.
[Chakrapani, Anupam] Birmingham Childrens Hosp, Birmingham, W Midlands, England.
RP Chapman, KA (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW,Suite 4800, Washington, DC 20010 USA.
EM kchapman@childrensnational.org
FU European Union [E-IMD 2010 12 01]
FX Special thanks to Dr. Brendan Lanpher for his critical review and
editing of this manuscript. This publication arises from the project
'E-IMD 2010 12 01' which has received funding from the European Union,
in the framework of the Health Programme.
NR 53
TC 25
Z9 29
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2012
VL 105
IS 1
BP 16
EP 25
DI 10.1016/j.ymgme.2011.09.026
PG 10
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 879WO
UT WOS:000299363800005
PM 22000903
ER
PT J
AU Sutton, VR
Chapman, KA
Gropman, AL
MacLeod, E
Stagni, K
Summar, ML
Ueda, K
Mew, NA
Franks, J
Island, E
Matern, D
Pena, L
Smith, B
Urv, T
Venditti, C
Chakarapani, A
AF Sutton, V. Reid
Chapman, Kimberly A.
Gropman, Andrea L.
MacLeod, Erin
Stagni, Kathy
Summar, Marshall L.
Ueda, Keiko
Mew, Nicholas Ah
Franks, Jill
Island, Eddie
Matern, Dietrich
Pena, Loren
Smith, Brittany
Urv, Tina
Venditti, Charles
Chakarapani, Anupam
TI Chronic management and health supervision of individuals with propionic
acidemia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Propionic acidemia; Organic acidemia; Propionic aciduria; Organic
aciduria; Chronic management; Health supervision
ID LIVER-TRANSPLANTATION; METHYLMALONIC ACIDEMIA; PARENTERAL-NUTRITION;
ACUTE-PANCREATITIS; ORGANIC ACIDURIAS; INBORN-ERRORS; L-CARNITINE;
DISORDERS; METABOLISM; CHILDREN
AB Propionic acidemia is a relatively rare inborn error of metabolism. Individuals with propionic acidemia often have life-threatening episodes of hyperammonemia and metabolic acidosis, as well as intellectual disability. There are many reports of additional problems, including poor growth, stroke-like episodes of the basal ganglia, seizures, cardiomyopathy, long QTc syndrome, immune defects, pancreatitis and optic neuropathy: however, there is little information about the incidence of these problems in this rare disease. Additionally, there are no clear guidelines for medical or surgical management of individuals with propionic acidemia. Through a comprehensive and systematic review of the current medical literature and survey of expert opinion, we have developed practice guidelines for the chronic management of individuals with propionic acidemia, including dietary therapy, use of medications, laboratory monitoring, chronic health supervision, use of gastrostomy tubes and liver transplantation.
C1 [Sutton, V. Reid] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Sutton, V. Reid] Texas Childrens Hosp, Houston, TX 77030 USA.
[Chapman, Kimberly A.; Gropman, Andrea L.; MacLeod, Erin; Summar, Marshall L.; Mew, Nicholas Ah] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Stagni, Kathy] Organ Acidemia Assoc, Pinole, CA USA.
[Ueda, Keiko] Tufts Med Ctr, Boston, MA USA.
[Franks, Jill; Smith, Brittany] Propion Acidemia Fdn, Highland, IL USA.
[Island, Eddie] Georgetown Univ, Transplant Program, Washington, DC USA.
[Matern, Dietrich] Mayo Clin, Rochester, MN USA.
[Pena, Loren] Univ Illinois, Coll Med Chicago, Chicago, IL USA.
[Urv, Tina; Venditti, Charles] NIH, Bethesda, MD 20892 USA.
[Chakarapani, Anupam] Birmingham Childrens Hosp, Birmingham, W Midlands, England.
RP Sutton, VR (reprint author), 6701 Fannin,Suite 1560-10, Houston, TX 77030 USA.
EM vrsutton@texaschildrens.org
NR 61
TC 29
Z9 29
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2012
VL 105
IS 1
BP 26
EP 33
DI 10.1016/j.ymgme.2011.08.034
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 879WO
UT WOS:000299363800006
PM 21963082
ER
PT J
AU Okugawa, S
Moayeri, M
Pomerantsev, AP
Sastalla, I
Crown, D
Gupta, PK
Leppla, SH
AF Okugawa, Shu
Moayeri, Mahtab
Pomerantsev, Andrei P.
Sastalla, Inka
Crown, Devorah
Gupta, Pradeep K.
Leppla, Stephen H.
TI Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is
required for efficient spore germination and full virulence of Bacillus
anthracis
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID GRAM-POSITIVE BACTERIA; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI;
STREPTOCOCCUS-PNEUMONIAE; PROTECTIVE ANTIGEN; LIPID MODIFICATION;
PROTEIN SECRETION; IN-VITRO; SUBTILIS; IDENTIFICATION
AB Bacterial lipoproteins play a crucial role in virulence in some Gram-positive bacteria. However, the role of lipoprotein biosynthesis in Bacillus anthracis is unknown. We created a B. anthracis mutant strain altered in lipoproteins by deleting the lgt gene encoding the enzyme prolipoprotein diacylglyceryl transferase, which attaches the lipid anchor to prolipoproteins. 14C-palmitate labelling confirmed that the mutant strain lacked lipoproteins, and hydrocarbon partitioning showed it to have decreased surface hydrophobicity. The anthrax toxin proteins were secreted from the mutant strain at nearly the same levels as from the wild-type strain. The TLR2-dependent TNF-a response of macrophages to heat-killed lgt mutant bacteria was reduced. Spores of the lgt mutant germinated inefficiently in vitro and in mouse skin. As a result, in a murine subcutaneous infection model, lgt mutant spores had markedly attenuated virulence. In contrast, vegetative cells of the lgt mutant were as virulent as those of the wild-type strain. Thus, lipoprotein biosynthesis in B. anthracis is required for full virulence in a murine infection model.
C1 [Okugawa, Shu; Moayeri, Mahtab; Pomerantsev, Andrei P.; Sastalla, Inka; Crown, Devorah; Gupta, Pradeep K.; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX We thank Alan Sher for kindly providing TLR2-deficient mice and Drs.
Akira and Merkel for MyD88 knockout mice. We also thank Mini Varughese
for editing the manuscript. This research was supported by the
Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases.
NR 60
TC 14
Z9 14
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JAN
PY 2012
VL 83
IS 1
BP 96
EP 109
DI 10.1111/j.1365-2958.2011.07915.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 869GL
UT WOS:000298585600010
PM 22103323
ER
PT J
AU Wu, PH
Hale, CM
Chen, WC
Lee, JSH
Tseng, Y
Wirtz, D
AF Wu, Pei-Hsun
Hale, Christopher M.
Chen, Wei-Chiang
Lee, Jerry S. H.
Tseng, Yiider
Wirtz, Denis
TI High-throughput ballistic injection nanorheology to measure cell
mechanics
SO NATURE PROTOCOLS
LA English
DT Article
ID PARTICLE-TRACKING MICRORHEOLOGY; DIFFUSING WAVE SPECTROSCOPY;
ACTIN-FILAMENT NETWORKS; ATOMIC-FORCE MICROSCOPY; LIVING CELLS;
INTRACELLULAR NANORHEOLOGY; ENDOTHELIAL-CELLS; MATRIX STIFFNESS;
MAMMALIAN-CELLS; COMPLEX FLUIDS
AB High-throughput ballistic injection nanorheology is a method for the quantitative study of cell mechanics. Cell mechanics are measured by ballistic injection of submicron particles into the cytoplasm of living cells and tracking the spontaneous displacement of the particles at high spatial resolution. The trajectories of the cytoplasm-embedded particles are transformed into mean-squared displacements, which are subsequently transformed into frequency-dependent viscoelastic moduli and time-dependent creep compliance of the cytoplasm. This method allows for the study of a wide range of cellular conditions, including cells inside a 3D matrix, cell subjected to shear flows and biochemical stimuli, and cells in a live animal. Ballistic injection lasts <1 min and is followed by overnight incubation. Multiple particle tracking for one cell lasts <1 min. Forty cells can be examined in <1 h.
C1 [Wu, Pei-Hsun; Hale, Christopher M.; Chen, Wei-Chiang; Tseng, Yiider; Wirtz, Denis] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA.
[Wu, Pei-Hsun; Hale, Christopher M.; Chen, Wei-Chiang; Lee, Jerry S. H.; Wirtz, Denis] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA.
[Lee, Jerry S. H.] NCI, Ctr Strateg Sci Initiat, Off Director, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Tseng, Yiider] Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA.
RP Tseng, Y (reprint author), Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA.
EM ytseng@che.ufl.edu; wirtz@jhu.edu
RI Lee, Jerry/A-3189-2008; Lee, Jerry/K-4553-2014; Hale,
Christopher/A-6633-2009
OI Lee, Jerry/0000-0003-1515-0952; Hale, Christopher/0000-0002-2360-7759
FU NIH [U54CA143868, R21CA137686, R01GM084204]
FX Normal human ovarian epithelial cells (OSE10) and ovarian cancer cells
(OVCAR3) were provided by I.-M. Shih (Department of Pathology, Johns
Hopkins University School of Medicine). This work was supported in part
by NIH grants U54CA143868 and R21CA137686, and R01GM084204. We thank
members of the Wirtz and Tseng labs for technical advice and reagents.
NR 73
TC 20
Z9 20
U1 2
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD JAN
PY 2012
VL 7
IS 1
BP 155
EP 170
DI 10.1038/nprot.2011.436
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 876LL
UT WOS:000299108900014
PM 22222790
ER
PT J
AU Pommier, Y
Marchand, C
AF Pommier, Yves
Marchand, Christophe
TI Interfacial inhibitors: targeting macromolecular complexes
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID DNA TOPOISOMERASE-II; BREAKAGE-REUNION REACTION; X-RAY STRUCTURES;
CRYSTAL-STRUCTURE; STRUCTURAL BASIS; ANTITUMOR DRUGS; INTEGRASE
INHIBITORS; ALLOSTERIC PROTEINS; HUMAN CALCINEURIN; COVALENT COMPLEX
AB Interfacial inhibitors belong to a broad class of natural products and synthetic drugs that are commonly used to treat cancers as well as bacterial and HIV infections. They bind selectively to interfaces as macromolecular machines assemble and are set in motion. The bound drugs transiently arrest the targeted molecular machines, which can initiate allosteric effects, or desynchronize macromolecular machines that normally function in concert. Here, we review five archetypical examples of interfacial inhibitors: the camptothecins, etoposide, the quinolone antibiotics, the vinca alkaloids and the novel anti-HIV inhibitor raltegravir. We discuss the common and diverging elements between interfacial and allosteric inhibitors and give a perspective for the rationale and methods used to discover novel interfacial inhibitors.
C1 [Pommier, Yves; Marchand, Christophe] NCI, Mol Pharmacol Lab, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research, the National Cancer Institute, US National
Institutes of Health
FX Our studies are supported by the Center for Cancer Research, the
Intramural Program of the National Cancer Institute, US National
Institutes of Health.
NR 83
TC 90
Z9 90
U1 5
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD JAN
PY 2012
VL 11
IS 1
BP 25
EP 36
DI 10.1038/nrd3404
PG 12
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 879IO
UT WOS:000299323100019
PM 22173432
ER
PT J
AU Gupta, S
Gellert, M
Yang, W
AF Gupta, Shikha
Gellert, Martin
Yang, Wei
TI Mechanism of mismatch recognition revealed by human MutS beta bound to
unpaired DNA loops
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID REPAIR PROTEIN MUTS; SACCHAROMYCES-CEREVISIAE; REPEAT INSTABILITY;
COLORECTAL-CANCER; YEAST MSH2-MSH6; ATPASE ACTIVITY; HMUTS-BETA;
IN-VIVO; MSH6; BINDING
AB DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutS alpha is well characterized. We report here crystal structures of human MutS beta in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutS alpha and bacterial MutS, which bind the base of a mismatched nucleotide, MutS beta binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutS beta. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.
C1 [Gupta, Shikha; Gellert, Martin; Yang, Wei] NIDDKD, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU National Institute of Diabetes and Digestive and Kidney Diseases, US
National Institutes of Health
FX We thank J. Jiang for collecting X-ray diffraction data of Loop4; A.
Howard for help with data processing; T. Kunkel for the term
'isomerization'; R. Kolodner, E. Alani and J. Surtees for vital
discussions; and D. Leahy for critical reading of the manuscript. The
research of all authors was funded by the intramural research program of
the National Institute of Diabetes and Digestive and Kidney Diseases, US
National Institutes of Health.
NR 53
TC 48
Z9 48
U1 1
U2 11
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 JAN
PY 2012
VL 19
IS 1
BP 72
EP U91
DI 10.1038/nsmb.2175
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 875PW
UT WOS:000299046000012
PM 22179786
ER
PT J
AU Leischow, SJ
Zeller, M
Backinger, CL
AF Leischow, Scott J.
Zeller, Mitch
Backinger, Cathy L.
TI Research Priorities and Infrastructure Needs of the Family Smoking
Prevention and Tobacco Control Act: Science to Inform FDA Policy
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Editorial Material
AB Introduction: A new law in the United States gives the Food and Drug Administration (FDA) wide latitude to regulate tobacco products for the first time. Given the need for science to serve as a foundation for FDA actions, it is critical that a scientific review of the literature relevant to the proposed legislation be undertaken by experts in the field of nicotine and tobacco research in order to develop research priorities.
Methods: This paper describes an initiative that was implemented to identify research opportunities under "The Family Smoking Prevention and Tobacco Control Act" and summarizes the conclusions and future directions derived from that initiative.
Results: Multiple research and surveillance needs were identified, such as characterization of biomarkers and increased analysis of risk perception. It was also recognized that science will play a critical role in policy determinations such as what constitutes "substantial equivalence" and that there will be considerable infrastructure needs (e. g., laboratories for product testing).
Conclusions: Science must drive FDA's decision making regarding tobacco regulation. This article provides a summary of research opportunities identified through literature reviews related to various provisions of the new law. However, the science required by the law requires a transdisciplinary approach because of its complexity, so one of the challenges facing the FDA will be to connect the silos of research in recognition that the "system" of tobacco regulation is greater than the sum of its parts.
C1 [Leischow, Scott J.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Zeller, Mitch] Pinney Associates, Bethesda, MD USA.
[Backinger, Cathy L.] NCI, Bethesda, MD 20892 USA.
RP Leischow, SJ (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA.
EM sleischow@azcc.arizona.edu
NR 7
TC 13
Z9 13
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JAN
PY 2012
VL 14
IS 1
BP 1
EP 6
DI 10.1093/ntr/ntr057
PG 6
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 877YS
UT WOS:000299219200001
PM 22184581
ER
PT J
AU Basel-Vanagaite, L
Sprecher, E
Gat, A
Merlob, P
Albin-Kaplanski, A
Konen, O
Solomon, BD
Muenke, M
Grzeschik, KH
Sirota, L
AF Basel-Vanagaite, Lina
Sprecher, Eli
Gat, Andrea
Merlob, Paul
Albin-Kaplanski, Adi
Konen, Osnat
Solomon, Benjamin D.
Muenke, Maximilian
Grzeschik, Karl H.
Sirota, Lea
TI New Syndrome of Congenital Circumferential Skin Folds Associated with
Multiple Congenital Anomalies
SO PEDIATRIC DERMATOLOGY
LA English
DT Article
ID MICHELIN-TIRE BABY; AUTOSOMAL DOMINANT TRAIT; SMOOTH-MUSCLE HAMARTOMA;
MCA/MR SYNDROME; CREASES; MUTATIONS; SPECTRUM; NEVUS; GENE
AB Congenital circumferential skin folds can be found in individuals with no additional defects, as well as in patients with multiple congenital anomalies and developmental abnormalities. Current data point to etiological heterogeneity of syndromic cases. We describe a 7-month-old girl with a novel combination of symmetrical congenital circumferential skin folds, dysmorphic features, and multiple congenital abnormalities. Examination of the patient revealed symmetrical congenital circumferential skin folds and dysmorphic features, as well as multiple congenital anomalies including nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy demonstrated subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. Extensive review of previously described cases of syndromic congenital circumferential skin folds did not reveal a similar combination of clinical and histopathological findings.
C1 [Basel-Vanagaite, Lina] Beilinson Med Ctr, Rabin Med Ctr, Schneider Childrens Med Ctr Israel, IL-49100 Petah Tiqwa, Israel.
[Basel-Vanagaite, Lina] Beilinson Med Ctr, Rabin Med Ctr, Raphael Recanati Genet Inst, IL-49100 Petah Tiqwa, Israel.
[Basel-Vanagaite, Lina; Sprecher, Eli; Gat, Andrea] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Sprecher, Eli] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Dermatol, IL-69978 Tel Aviv, Israel.
[Gat, Andrea] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Pathol, IL-69978 Tel Aviv, Israel.
[Sirota, Lea] Rabin Med Ctr, Dept Neonatol, Petah Tiqwa, Israel.
[Konen, Osnat] Schneider Childrens Med Ctr Israel, Dept Imaging, Petah Tiqwa, Israel.
[Albin-Kaplanski, Adi] Rabin Med Ctr, Raphael Recanati Genet Inst, Petah Tiqwa, Israel.
[Grzeschik, Karl H.] Univ Marburg, Dept Human Genet, Marburg, Germany.
[Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Basel-Vanagaite, L (reprint author), Beilinson Med Ctr, Rabin Med Ctr, Schneider Childrens Med Ctr Israel, IL-49100 Petah Tiqwa, Israel.
EM basel@post.tau.ac.il
FU Intramural NIH HHS [ZIA HG000209-12]
NR 32
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-8046
J9 PEDIATR DERMATOL
JI Pediatr. Dermatol.
PD JAN-FEB
PY 2012
VL 29
IS 1
BP 89
EP 95
DI 10.1111/j.1525-1470.2011.01403.x
PG 7
WC Dermatology; Pediatrics
SC Dermatology; Pediatrics
GA 877UX
UT WOS:000299209300016
PM 21995818
ER
PT J
AU Komarow, HD
Skinner, J
Young, M
Gaskins, D
Nelson, C
Gergen, PJ
Metcalfe, DD
AF Komarow, Hirsh D.
Skinner, Jeff
Young, Michael
Gaskins, Donna
Nelson, Celeste
Gergen, Peter J.
Metcalfe, Dean D.
TI A study of the use of impulse oscillometry in the evaluation of children
with asthma: Analysis of lung parameters, order effect, and utility
compared with spirometry
SO PEDIATRIC PULMONOLOGY
LA English
DT Article
DE pediatric asthma; lung function; bronchodilator response; spirometry;
impulse oscillometry
ID FORCED OSCILLATION TECHNIQUE; REFERENCE VALUES; BRONCHODILATOR RESPONSE;
RESPIRATORY RESISTANCE; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; IMPEDANCE;
HEALTHY; RISK
AB Background The ability to objectively measure lung function in children is critical in the assessment and treatment of asthma in this age group. We thus determined the effectiveness of impulse oscillometry (IOS) as a non-invasive technique to assess lung function in children and in comparison to spirometry for sensitivity and specificity, testing variability, and the order effect of sequential testing of IOS and spirometry.Methods: One hundred seventeen children sequentially evaluated in a pediatric clinic and under medical care for disease, were asked to perform IOS and spirometry. The utility of IOS and spirometry in differentiating children that had asthma versus those children who did not was then analyzed. Results: In the primary analysis (n = 117), bronchodilator response using IOS distinguished asthmatics from non- asthmatics, P = 0.0008 for R10. Receiver- operator characteristic curve (ROC) analysis of R10 bronchodilator response at the best cut- off (-8.6% change) correctly identified 77% of patients with asthma and excluded 76% of non- asthmatics. Amongst those children able to perform spirometry (asthmatics, n = 66; non- asthmatics, n = 16), FEV1 did not reveal a difference between these two groups, while area of reactance (AX) did distinguish these groups (P = 0.0092). Sequential testing of IOS and then spirometry (n = 47) showed a significant decrement in lung function as determined by IOS following performance of spirometry (P = 0.0309). Conclusion: In the diagnosis and management of children with lung disease, IOS is a non- invasive approach that easily and objectively measures lung impedance and should be considered as both an adjunct, and in some situations, an alternative to standard spirometry. Pediatr Pulmonol. 2012; 47: 18- 26. (C) 2011 Wiley Periodicals, Inc.
C1 [Komarow, Hirsh D.; Young, Michael; Gaskins, Donna; Nelson, Celeste; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff] NIAID, BCBB, NIH, Bethesda, MD 20892 USA.
[Gergen, Peter J.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
RP Komarow, HD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
OI Skinner, Jeff/0000-0001-5697-0442
FU Division of Intramural Research of NIAID, NIH
FX Division of Intramural Research of NIAID, NIH.
NR 30
TC 23
Z9 28
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 8755-6863
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD JAN
PY 2012
VL 47
IS 1
BP 18
EP 26
DI 10.1002/ppul.21507
PG 9
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA 869IE
UT WOS:000298590800003
PM 22170806
ER
PT J
AU Kinsinger, CR
Apffel, J
Baker, M
Bian, XP
Borchers, CH
Bradshaw, R
Brusniak, MY
Chan, DW
Deutsch, EW
Domon, B
Gorman, J
Grimm, R
Hancock, W
Hermjakob, H
Horn, D
Hunter, C
Kolar, P
Kraus, HJ
Langen, H
Linding, R
Moritz, RL
Omenn, GS
Orlando, R
Pandey, A
Ping, PP
Rahbar, A
Rivers, R
Seymour, SL
Simpson, RJ
Slotta, D
Smith, RD
Stein, SE
Tabb, DL
Tagle, D
Yates, JR
Rodriguez, H
AF Kinsinger, Christopher R.
Apffel, James
Baker, Mark
Bian, Xiaopeng
Borchers, Christoph H.
Bradshaw, Ralph
Brusniak, Mi-Youn
Chan, Daniel W.
Deutsch, Eric W.
Domon, Bruno
Gorman, Jeff
Grimm, Rudolf
Hancock, William
Hermjakob, Henning
Horn, David
Hunter, Christie
Kolar, Patrik
Kraus, Hans-Joachim
Langen, Hanno
Linding, Rune
Moritz, Robert L.
Omenn, Gilbert S.
Orlando, Ron
Pandey, Akhilesh
Ping, Peipei
Rahbar, Amir
Rivers, Robert
Seymour, Sean L.
Simpson, Richard J.
Slotta, Douglas
Smith, Richard D.
Stein, Stephen E.
Tabb, David L.
Tagle, Danilo
Yates, John R.
Rodriguez, Henry
TI Recommendations for mass spectrometry data quality metrics for open
access data (corollary to the Amsterdam principles)
SO PROTEOMICS
LA English
DT Article
DE Amsterdam principles; Bioinformatics; Data quality; Metrics; Open
access; Selected reaction monitoring; Standards
ID PROTEIN IDENTIFICATION DATA; SHOTGUN PROTEOMICS; PEPTIDE IDENTIFICATION;
CLINICAL PROTEOMICS; MINIMUM INFORMATION; STATISTICAL-MODEL; GUIDELINES;
RESOURCE; SPECTRA; REPRODUCIBILITY
AB Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the International Workshop on Proteomic Data Quality Metrics in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed upon two primary needs for the wide use of quality metrics: (i) an evolving list of comprehensive quality metrics and (ii) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in Proteomics, Proteomics Clinical Applications, Journal of Proteome Research, and Molecular and Cellular Proteomics, as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.
C1 [Kinsinger, Christopher R.; Rahbar, Amir; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA.
[Apffel, James] Agilent Res Labs, Santa Clara, CA USA.
[Baker, Mark] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia.
[Bian, Xiaopeng] NCI, Ctr Bioinformat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Borchers, Christoph H.] Univ Victoria, Genome BC Prote Ctr, Victoria, BC, Canada.
[Bradshaw, Ralph] Univ Calif San Francisco, Mass Spectrometry Facil, San Francisco, CA 94143 USA.
[Chan, Daniel W.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Domon, Bruno] CRP Sante, Luxembourg Clin Prote Ctr, Luxembourg, Luxembourg.
[Gorman, Jeff] Queensland Inst Med Res, Prot Discovery Ctr, Herston, Qld 4006, Australia.
[Grimm, Rudolf] Agilent Technol, Santa Clara, CA USA.
[Hancock, William] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Hermjakob, Henning] European Bioinformat Inst, Prote Serv, Cambridge, England.
[Horn, David] Thermo Fisher Sci, Prote Software Strateg Mkt, San Jose, CA USA.
[Hunter, Christie; Rivers, Robert] AB SCIEX, Foster City, AB, Canada.
[Kolar, Patrik] European Commiss, Directorate Gen Res, Brussels, Belgium.
[Kraus, Hans-Joachim] Wiley VCH, Weinheim, Germany.
[Langen, Hanno] Hoffmann La Roche Ag, Exploratory Biomarkers, CH-4002 Basel, Switzerland.
[Linding, Rune] Tech Univ Denmark DTU, Cellular Signal Integrat Grp C SIG, Ctr Biol Sequence Anal CBS, Dept Syst Biol, Lyngby, Denmark.
[Moritz, Robert L.] Inst Syst Biol, Cellular & Mol Logic Unit, Seattle, WA USA.
[Omenn, Gilbert S.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Orlando, Ron] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Seymour, Sean L.] NCI, Small Business Dev Ctr, NIH, Bethesda, MD 20892 USA.
[Simpson, Richard J.] La Trobe Univ, La Trobe Inst Mol Sci, Bundoora, Vic, Australia.
[Slotta, Douglas] NIH, Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Smith, Richard D.] Pacific NW Natl Lab, Richland, WA 99352 USA.
[Stein, Stephen E.] NIST, Chem Reference Data Grp, Gaithersburg, MD 20899 USA.
[Tabb, David L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Tagle, Danilo] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Yates, John R.] Scripps Res Inst, La Jolla, CA 92037 USA.
RP Kinsinger, CR (reprint author), NCI, Off Canc Clin Prote Res, NIH, 31 Ctr Dr,MSC 2580, Bethesda, MD 20892 USA.
EM kinsingc@mail.nih.gov
RI Pandey, Akhilesh/B-4127-2009; Smith, Richard/J-3664-2012; Bradshaw,
Ralph/K-1515-2013;
OI Hermjakob, Henning/0000-0001-8479-0262; Baker, Mark/0000-0001-5858-4035;
Pandey, Akhilesh/0000-0001-9943-6127; Smith,
Richard/0000-0002-2381-2349; Ping, Peipei/0000-0003-3583-3881; Omenn,
Gilbert S./0000-0002-8976-6074
NR 51
TC 18
Z9 18
U1 1
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD JAN
PY 2012
VL 12
IS 1
BP 11
EP 20
DI 10.1002/pmic.201100562
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 872WL
UT WOS:000298841000004
PM 22069307
ER
PT J
AU Bacigalupo, A
Chien, J
Barisione, G
Pavletic, S
AF Bacigalupo, Andrea
Chien, Jason
Barisione, Giovanni
Pavletic, Steven
TI Late Pulmonary Complications After Allogeneic Hematopoietic Stem Cell
Transplantation: Diagnosis, Monitoring, Prevention, and Treatment
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID VERSUS-HOST-DISEASE; BRONCHIOLITIS OBLITERANS SYNDROME; CONSENSUS
DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BONE-MARROW TRANSPLANTATION;
CHRONIC MYELOGENOUS LEUKEMIA; UNRELATED DONORS; RANDOMIZED-TRIAL;
CLINICAL-TRIALS; ANTITHYMOCYTE GLOBULIN
AB Bronchiolitis obliterans syndrome (BOS) is a life-threatening complication that occurs among recipients of allogeneic lung and hematopoietic stem cell transplantation (allo-HSCT). BOS usually occurs within the first 2 years but may develop as late as 5 years after allo-HSCT. Recent prevalence estimates suggest that BOS is likely underdiagnosed in the clinical setting and that 14% of all long-term survivors with chronic graft-versus-host disease (GVHD) may develop BOS. It is difficult to diagnose and once respiratory symptoms appear, most allo-HSCT recipients show severe airflow obstruction. This may be due, at least in part, to the low sensitivity of standard spirometry in detecting small airways obstruction and lack of formal recommendations for screening for this complication. The prognosis of BOS is poor with reported 5-year survival of about 15%. A key obstacle in advancing clinical research in BOS is the lack of diagnostic and therapeutic response standards, making interpretation of survival and treatment results between studies difficult. This situation has significantly improved due to the introduction of the National Institutes of Health (NIH) criteria, which provide investigators with common definitions for studying BOS and for assessing the effects of therapeutic interventions. Future advances in the therapy of BOS may need to include development of better early intervention strategies based on identification of reliable early biological markers of the disease. It would be also important to improve understanding of the biological heterogeneity of this devastating complication after allo-HSCT. Semin Hematol 49:15-24. (C) 2012 Published by Elsevier Inc.
C1 [Bacigalupo, Andrea] Azienda Osped Univ San Martino, Unita Operat Ematol 2, I-16132 Genoa, Italy.
[Chien, Jason] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Barisione, Giovanni] Azienda Osped Univ San Martino, Unita Operat Med Prevent & Lavoro, Lab Fisiopatol Resp, I-16132 Genoa, Italy.
[Pavletic, Steven] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Bacigalupo, A (reprint author), Azienda Osped Univ San Martino, Unita Operat Ematol 2, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
EM andrea.bacigalupo@hsanmartino.it
FU Associazione Italiana Ricerca contro il Cancro (A.I.R.C.), Milano;
Fondazione Ricerca Trapianto di Midollo Osseo (FA-RI.T.M.O.), Genova,
Italy
FX This work was supported by Associazione Italiana Ricerca contro il
Cancro (A.I.R.C.), Milano, and Fondazione Ricerca Trapianto di Midollo
Osseo (FA-RI.T.M.O.), Genova, Italy
NR 53
TC 21
Z9 21
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JAN
PY 2012
VL 49
IS 1
BP 15
EP 24
DI 10.1053/j.seminhematol.2011.10.005
PG 10
WC Hematology
SC Hematology
GA 880JE
UT WOS:000299402600004
PM 22221781
ER
PT J
AU Shanis, D
Merideth, M
Pulanic, TK
Savani, BN
Battiwalla, M
Stratton, P
AF Shanis, Dana
Merideth, Melissa
Pulanic, Tajana Klepac
Savani, Bipin N.
Battiwalla, Minoo
Stratton, Pamela
TI Female Long-Term Survivors After Allogeneic Hematopoietic Stem Cell
Transplantation: Evaluation and Management
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TOTAL-BODY
IRRADIATION; PREMATURE OVARIAN FAILURE; QUALITY-OF-LIFE; CONSENSUS
DEVELOPMENT PROJECT; HUMAN-PAPILLOMAVIRUS HPV; VIRUS-LIKE PARTICLES;
WORKING GROUP-REPORT; CHRONIC GRAFT
AB Female long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) incur a significant burden of late effects. Genital graft-versus-host disease (GVHD), human papillomavinis (HPV) reactivation, ovarian failure and infertility, sexual dysfunction, and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation, and implications of these common complications. Recommendations are provided for evaluation and management of these late effects and other obstetric and gynecologic issues that may arise in this patient population. Semin Hematol 49:83-93. Published by Elsevier Inc.
C1 [Stratton, Pamela] Eunice Kennedy Schriver NICHD, Head Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC,NIH, Bethesda, MD 20892 USA.
[Merideth, Melissa] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Merideth, Melissa] Intramural Off Rare Dis, NIH, Bethesda, MD USA.
[Pulanic, Tajana Klepac] Community Hlth Ctr E, Zagreb, Croatia.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Nashville, TN USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Stratton, P (reprint author), Eunice Kennedy Schriver NICHD, Head Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC,NIH, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM strattop@mail.nih.gov
FU NIH Clinical Center; NHLBI; NICHD; NHGRI; NIH; American College of
Obstetricians and Gynecologists
FX This work was supported in part by the Intramural Research Program of
the NIH Clinical Center, NHLBI, NICHD, and NHGRI; 2008 NIH Intramural
bench to bedside award to NICHD, NHLBI, and NCI: women's health category
and 2011-2012 American College of Obstetricians and
Gynecologists/Hologic Research Award on Cervical Cancer Prevention.
NR 82
TC 19
Z9 19
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 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JAN
PY 2012
VL 49
IS 1
BP 83
EP 93
DI 10.1053/j.seminhematol.2011.10.002
PG 11
WC Hematology
SC Hematology
GA 880JE
UT WOS:000299402600011
PM 22221788
ER
PT J
AU Than, NG
Romero, R
Kim, CJ
McGowen, MR
Papp, Z
Wildman, DE
AF Than, Nandor Gabor
Romero, Roberto
Kim, Chong Jai
McGowen, Michael R.
Papp, Zoltan
Wildman, Derek E.
TI Galectins: guardians of eutherian pregnancy at the maternal-fetal
interface
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID GALACTOSIDE-BINDING LECTINS; LEYDEN CRYSTAL PROTEIN;
NATURAL-KILLER-CELLS; REGULATORY T-CELLS; PHYLOGENETIC ANALYSIS;
PLACENTAL EXPRESSION; SEVERE PREECLAMPSIA; PROTEOMIC ANALYSIS; IMMUNE
TOLERANCE; ANIMAL LECTINS
AB Galectins are multifunctional regulators of fundamental cellular processes. They are also involved in innate and adaptive immune responses, and play a functional role in immune-endocrine crosstalk. Some galectins have attracted attention in the reproductive sciences because they are highly expressed at the maternal-fetal interface, their functional significance in eutherian pregnancies has been documented, and their dysregulated expression is observed in the 'great obstetrical syndromes'. The evolution of these galectins has been linked to the emergence of eutherian mammals. Based on published evidence, galectins expressed at the maternal-fetal interface may serve as important proteins involved in maternal-fetal interactions, and the study of these galectins may facilitate the prediction, prevention, diagnosis, and treatment of pregnancy complications.
C1 [Than, Nandor Gabor; Romero, Roberto; Kim, Chong Jai; Wildman, Derek E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Than, Nandor Gabor; Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary.
[McGowen, Michael R.; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
[Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Than, NG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
EM nthan@med.wayne.edu; prbchiefstaff@med.wayne.edu; dwildman@wayne.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; National Science Foundation [BCS-0827546];
European Union [037244]
FX We thank Prof Dr Peter Zavodszky and Dr Andras Szilagyi (Hungarian
Academy of Sciences) for constructing Figures 3c and 3d and for their
permission to re-use these images; Dr Adi Tarca and Gaurav Bhatti (Wayne
State University) for their assistance in computations; Pat Schoff
(Wayne State University) and Valerie Richardson for art work; and
Maureen McGerty and Sara Tipton (Wayne State University) for their
critical readings of the manuscript. This research was supported by the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; the National Science Foundation (BCS-0827546);
and the European Union FP6 Program (Pregenesys; 037244).
NR 84
TC 36
Z9 36
U1 1
U2 18
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD JAN
PY 2012
VL 23
IS 1
BP 23
EP 31
DI 10.1016/j.tem.2011.09.003
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 881AE
UT WOS:000299450900004
PM 22036528
ER
PT J
AU Muthana, SM
Campbell, CT
Gildersleeve, JC
AF Muthana, Saddam M.
Campbell, Christopher T.
Gildersleeve, Jeffrey C.
TI Modifications of Glycans: Biological Significance and Therapeutic
Opportunities
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
DE Carbohydrate; Glycan; Post-glycosylational modification; Sulfation;
Phosphorylation; Acylation; Methylation
ID CHONDROITIN SULFATE PROTEOGLYCANS; MUCOID PSEUDOMONAS-AERUGINOSA;
ACETYLATED SIALIC ACIDS; DE-ORTHO-ACETYLATION; WALL TEICHOIC-ACID;
N-LINKED GLYCANS; O-ACETYLATION; STAPHYLOCOCCUS-AUREUS; HEPARAN-SULFATE;
L-SELECTIN
AB Carbohydrates play a central role in a wide range of biological processes. As with nucleic acids and proteins, modifications of specific sites within the glycan chain can modulate a carbohydrate's overall biological function. For example, acylation, methylation, sulfation, epimerization, and phosphorylation can occur at various positions within a carbohydrate to modulate bioactivity. Therefore, there is significant interest in identifying discrete carbohydrate modifications and understanding,their biological effects. Additionally, enzymes that catalyze those modifications and proteins that bind modified glycans provide numerous targets for therapeutic intervention. This review will focus on modifications of glycans that occur after the oligomer/polymer has been assembled, generally referred to as post-glycosylational modifications.
C1 [Muthana, Saddam M.; Campbell, Christopher T.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
RI Gildersleeve, Jeffrey/N-3392-2014
FU National Institutes of Health, NCI; Pharmacology Research Associate
(PRAT) of the NIGMS
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, NCI. C.T.C. received fellowship support
from the Pharmacology Research Associate (PRAT) program of the NIGMS.
NR 144
TC 36
Z9 36
U1 5
U2 44
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 JAN
PY 2012
VL 7
IS 1
BP 31
EP 43
DI 10.1021/cb2004466
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 878FQ
UT WOS:000299241300005
PM 22195988
ER
PT J
AU Chandran, PL
Horkay, F
AF Chandran, Preethi L.
Horkay, Ferenc
TI Aggrecan, an unusual polyelectrolyte: Review of solution behavior and
physiological implications
SO ACTA BIOMATERIALIA
LA English
DT Review
DE Cartilage; Osmotic pressure; ECM; Light scattering; Viscoelasticity
ID ATOMIC-FORCE MICROSCOPY; CONNECTIVE-TISSUE POLYSACCHARIDES; CONFOCAL
FLUORESCENCE RECOVERY; SULFATE TRANSPORTER GENE; BOVINE NASAL CARTILAGE;
ARTICULAR-CARTILAGE; HYDRODYNAMIC PROPERTIES; VISCOELASTIC PROPERTIES;
PROTEOGLYCAN SOLUTIONS; IONIC-STRENGTH
AB Aggrecan is a high-molecular-weight, bottlebrush-shaped, negatively charged biopolymer that forms supermolecular complexes with hyaluronic acid. In the extracellular matrix of cartilage, aggrecan-hyaluronic acid complexes are interspersed in a collagen meshwork and provide the osmotic properties required to resist deswelling under compressive load. In this review we compile aggrecan solution behavior from different experimental techniques, and discuss them in the context of concentration regimes that were identified in osmotic pressure experiments. At low concentrations, aggrecan exhibits microgel-like behavior. With increasing concentration, the bottlebrushes self-assemble into large complexes. In the physiological concentration range (2 < c(aggrecan) < 8% w/w), the physical properties of the solution are dominated by repulsive electrostatic interactions between aggrecan complexes. We discuss the consequences of the bottlebrush architecture on the polyelectrolyte characteristics of the aggrecan molecule, and its implications for cartilage properties and function. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.
C1 [Chandran, Preethi L.; Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
[Chandran, Preethi L.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Chandran, PL (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bldg 13,13 South Dr, Bethesda, MD 20892 USA.
EM chandranlp@mail.nih.gov; horkay@helix.nih.gov
FU NICHD, NIH
FX This work was supported by the Intramural Research Program of the NICHD,
NIH. The authors are grateful to Dr. Peter Basser (NIH) and Dr. Jack
Douglas (NIST) for their thoughtful comments and suggestions.
NR 81
TC 22
Z9 22
U1 2
U2 33
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
J9 ACTA BIOMATER
JI Acta Biomater.
PD JAN
PY 2012
VL 8
IS 1
BP 3
EP 12
DI 10.1016/j.actbio.2011.08.011
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 871UP
UT WOS:000298763500001
PM 21884828
ER
PT J
AU Acosta, MT
Munashinge, J
Zhang, L
Guerron, DA
Vortmeyer, A
Theodore, WH
AF Acosta, M. T.
Munashinge, J.
Zhang, L.
Guerron, Daniel A.
Vortmeyer, Alexander
Theodore, W. H.
TI Isolated seizures in rats do not cause neuronal injury
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Article
DE seizures; neuroimaging; epilepsy
ID TEMPORAL-LOBE EPILEPSY; EXPERIMENTAL FEBRILE SEIZURES;
MAGNETIC-RESONANCE; STATUS-EPILEPTICUS; STRUCTURAL ALTERATIONS;
HIPPOCAMPAL DAMAGE; RECURRENT SEIZURES; ADULT RATS; MODEL; MRI
AB Background - Previous studies have shown that status epilepticus can lead to neuronal injury. However, the effect of a small number of isolated seizures is uncertain. Methods - We used structural MRI and neuropathology to study the effects of isolated seizures induced by kainic acid (KA), (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazole-4-yl)propanoic acid (ATPA), and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate in rats. A group of animals received normal saline. After seizure induction, animals were followed for 12 weeks. Results - ATPA and KA led to small but significant increases in ADC. There were no changes in T2 signal intensity or hippocampal volume. Blinded pathological examination showed no differences between animals receiving saline or glutamatergic agents. Conclusion - Our study suggests that isolated seizures cause minimal neuronal injury in rats.
C1 [Acosta, M. T.; Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Acosta, M. T.; Guerron, Daniel A.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Munashinge, J.; Zhang, L.; Guerron, Daniel A.] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Vortmeyer, Alexander] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
FU NIH NINDS Division of Intramural Research
FX This study was supported by the NIH NINDS Division of Intramural
Research.
NR 37
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-6314
J9 ACTA NEUROL SCAND
JI Acta Neurol. Scand.
PD JAN
PY 2012
VL 125
IS 1
BP 30
EP 37
DI 10.1111/j.1600-0404.2011.01521.x
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 867TN
UT WOS:000298477600008
PM 21615350
ER
PT J
AU Kovalchik, SA
AF Kovalchik, Stephanie A.
TI Mother's CD4(+) Count Moderates the Risk Associated with Higher Parity
for Late Postnatal HIV-Free Survival of Breastfed Children: An
Individual Patient Data Meta-Analysis of Randomized Controlled Trials
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Gravidity; Human Immunodeficiency Virus; Meta-analysis; Parity;
Prevention of maternal to child transmission of HIV; Risk factors
ID DAR-ES-SALAAM; ANTIRETROVIRAL THERAPY; POOLED ANALYSIS; INFANTS BORN;
TRANSMISSION; WOMEN; VIRUS; MILK; CHALLENGES; PREVENTION
AB Risk association studies of late postnatal outcomes for children breastfed by HIV-1 positive mothers have had inconsistent findings and have not explored interactions among risk factors. This study addresses these limitations through an individual patient data (IPD) meta-analysis of HIV-free survival outcomes of nine randomized controlled trials to prevent early mother-to-child transmission of HIV-1. The pooled sample consisted of 3,324 African children in resource-limited settings who survived to age 28 days and were at-risk of acquiring HIV through breast milk. Based on a proportional hazards mixed effects meta-analysis, the composite endpoint of HIV-1 infection and all-cause mortality was found to be significantly associated with maternal immune status (CD4(+) a parts per thousand yen350 cells/mm(3), HR 0.59 95% CI (0.39, 0.87)), infant preterm delivery (gestational age < 37 weeks, 1.40 (1.03, 1.89)), infant oral candidiasis infection (1.87, (1.53, 2.29)), and occurrence of breast abnormality before breastfeeding cessation (2.56 (1.90, 3.46)). A significant interaction between mother's parity (any previous pregnancy) and CD4(+) count a parts per thousand yen350 (HR 0.63 (0.40, 0.99), P-value = 0.045) suggested that higher CD4(+) count offsets the risk associated with higher parity. Further research is needed to elucidate the moderating effect of immune status on the risk associated with high parity and adverse late postnatal outcomes for infants breastfed by HIV-infected mothers in the absence of antiretroviral treatment.
C1 NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA.
RP Kovalchik, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Execut Blvd,EPS 8044, Rockville, MD 20852 USA.
EM kovalchiksa@mail.nih.gov
FU NIAID NIH HHS [N01-AI-35173, U01 AI069530, T32-AI007370]
NR 30
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD JAN
PY 2012
VL 16
IS 1
BP 79
EP 85
DI 10.1007/s10461-011-9989-8
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 875SI
UT WOS:000299054700011
PM 21739289
ER
PT J
AU Muniyappa, R
Sachdev, V
Sidenko, S
Ricks, M
Castillo, DC
Courville, AB
Sumner, AE
AF Muniyappa, Ranganath
Sachdev, Vandana
Sidenko, Stanislav
Ricks, Madia
Castillo, Darleen C.
Courville, Amber B.
Sumner, Anne E.
TI Postprandial endothelial function does not differ in women by race: an
insulin resistance paradox?
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE African Americans; endothelial function
ID AFRICAN-AMERICAN PATIENTS; FLOW-MEDIATED DILATION; HIGH-FAT MEAL;
VASCULAR REACTIVITY; RACIAL-DIFFERENCES; METABOLIC SYNDROME; OXIDATIVE
STRESS; BRACHIAL-ARTERY; ETHNIC-DIFFERENCES; DIABETES-MELLITUS
AB Muniyappa R, Sachdev V, Sidenko S, Ricks M, Castillo DC, Courville AB, Sumner AE. Postprandial endothelial function does not differ in women by race: an insulin resistance paradox? Am J Physiol Endocrinol Metab 302: E218-E225, 2012. First published November 1, 2011; doi: 10.1152/ajpendo.00434.2011.-Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 AfricanAmerican women, 18 white women) age-and body mass index (BMI)-matched (age: 37 +/- 11 yr; BMI: 30 +/- 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although AfricanAmerican women were less insulin-sensitive [insulin sensitivity index (mean +/- SD): 3.6 +/- 1.5 vs. 5.2 +/- 2.6, P = 0.02], both fasting triglyceride (TG: 56 +/- 37 vs. 97 +/- 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 +/- 190 vs. 492 +/- 255 mg.dl(-1).min(-1).10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group x time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.
C1 [Muniyappa, Ranganath] NIDDK, Diabet Endocrinol & Obes Branch, Intramural Program, Bethesda, MD 20892 USA.
[Sachdev, Vandana; Sidenko, Stanislav] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
RP Muniyappa, R (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, Intramural Program, 10 Ctr Dr,Bldg 10,Rm 4-1730,MSC 1302, Bethesda, MD 20892 USA.
EM muniyapr@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, and Blood Institute, National Institutes of Health
FX This work was supported by the Intramural Research Programs of National
Institute of Diabetes and Digestive and Kidney Diseases and National
Heart, Lung, and Blood Institute, National Institutes of Health.
NR 54
TC 6
Z9 6
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD JAN
PY 2012
VL 302
IS 2
BP E218
EP E225
DI 10.1152/ajpendo.00434.2011
PG 8
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 876MX
UT WOS:000299112700007
PM 22045315
ER
PT J
AU Motabar, O
Goldin, E
Leister, W
Liu, K
Southall, N
Huang, WW
Marugan, JJ
Sidransky, E
Zheng, W
AF Motabar, Omid
Goldin, Ehud
Leister, William
Liu, Ke
Southall, Noel
Huang, Wenwei
Marugan, Juan J.
Sidransky, Ellen
Zheng, Wei
TI A high throughput glucocerebrosidase assay using the natural substrate
glucosylceramide
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Glucocerebrosidase; Natural substrate; Gaucher disease; Enzyme
substrate; Inhibitor
ID LYSOSOMAL STORAGE DISORDERS; GAUCHER-DISEASE; BETA-GLUCOSIDASE; POMPE
DISEASE; THERAPY; LIVER; STRATEGIES; DIAGNOSIS; ACID
AB Glucocerebrosidase is a lysosomal enzyme that catalyzes the hydrolysis of glucosylceramide to form ceramide and glucose. A deficiency of lysosomal glucocerebrosidase due to genetic mutations results in Gaucher disease, in which glucosylceramide accumulates in the lysosomes of certain cell types. Although enzyme replacement therapy is currently available for the treatment of type 1 Gaucher disease, the neuronopathic forms of Gaucher disease are still not treatable. Small molecule drugs that can penetrate the blood-brain barrier, such as pharmacological chaperones and enzyme activators, are new therapeutic approaches for Gaucher disease. Enzyme assays for glucocerebrosidase are used to screen compound libraries to identify new lead compounds for drug development for the treatment of Gaucher disease. But the current assays use artificial substrates that are not physiologically relevant. We developed a glucocerebrosidase assay using the natural substrate glucosylceramide coupled to an Amplex-red enzyme reporting system. This assay is in a homogenous assay format and has been miniaturized in a 1,536-well plate format for high throughput screening. The assay sensitivity and robustness is similar to those seen with other glucocerebrosidase fluorescence assays. Therefore, this new glucocerebrosidase assay is an alternative approach for high throughput screening.
C1 [Motabar, Omid; Leister, William; Liu, Ke; Southall, Noel; Huang, Wenwei; Marugan, Juan J.; Zheng, Wei] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Motabar, Omid; Goldin, Ehud; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Zheng, W (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research;
National Human Genome Research Institute; National Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Programs of
the National Human Genome Research Institute and the National Institutes
of Health.
NR 24
TC 12
Z9 12
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JAN
PY 2012
VL 402
IS 2
BP 731
EP 739
DI 10.1007/s00216-011-5496-z
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 870BY
UT WOS:000298645300015
PM 22033823
ER
PT J
AU Orbach, Y
Lamb, ME
La Rooy, D
Pipe, ME
AF Orbach, Yael
Lamb, Michael E.
La Rooy, David
Pipe, Margaret-Ellen
TI A Case Study of Witness Consistency and Memory Recovery Across Multiple
Investigative Interviews
SO APPLIED COGNITIVE PSYCHOLOGY
LA English
DT Article
ID CHILDRENS EVENT REPORTS; EYEWITNESS MEMORY; SEXUAL-ABUSE; QUESTION TYPE;
ALLEGED VICTIMS; RECALL; HYPERMNESIA; PRESCHOOLERS; REMINISCENCE; DELAY
AB Access to audio recordings of five interviews (Interviews 26), and to the interviewer's contemporaneous notes during an initial unrecorded interview, made it possible to assess consistency across repeated attempts by a 9-year-old to describe her older sister's abduction from their shared bedroom. Information provided in each of the interviews was systematically analysed to determine whether each unit of information was new, consistent (repeated) or contradictory in relation to earlier reported information and whether any informative detail provided in the witness' initial interview was subsequently omitted. In addition, the witness' accounts were compared with details provided by the victim upon her rescue. This case analysis is particularly informative in light of widespread professional concerns about the effects of repeated interviewing on the quality and accuracy of children's accounts of experienced events. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Lamb, Michael E.] Univ Cambridge, Dept Social & Dev Psychol, Cambridge CB2 3RQ, England.
[Orbach, Yael] NICHHD, Bethesda, MD 20892 USA.
[La Rooy, David] Scottish Inst Policing Res, Dundee, Scotland.
[La Rooy, David] Univ Abertay Dundee, Dundee, Scotland.
[Pipe, Margaret-Ellen] CUNY Brooklyn Coll, New York, NY USA.
RP Lamb, ME (reprint author), Univ Cambridge, Dept Social & Dev Psychol, Free Sch Lane, Cambridge CB2 3RQ, England.
EM Mel37@cam.ac.uk
NR 77
TC 10
Z9 11
U1 3
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0888-4080
J9 APPL COGNITIVE PSYCH
JI Appl. Cogn. Psychol.
PD JAN-FEB
PY 2012
VL 26
IS 1
BP 118
EP 129
DI 10.1002/acp.1803
PG 12
WC Psychology, Experimental
SC Psychology
GA 877SU
UT WOS:000299203800012
ER
PT J
AU Bhaumik, P
Gustchina, A
Wlodawer, A
AF Bhaumik, Prasenjit
Gustchina, Alla
Wlodawer, Alexander
TI Structural studies of vacuolar plasmepsins
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Review
DE Aspartic protease; Malaria; Crystal structure; Plasmepsin; Inhibitors
ID HYDROXYMETHYLCARBONYL HMC ISOSTERE; PARASITE PLASMODIUM-FALCIPARUM;
ASPARTIC PROTEASE PLASMEPSIN; ACTIVE-SITE; CRYSTAL-STRUCTURES; FOOD
VACUOLE; POTENT INHIBITORS; ENZYMATIC CHARACTERIZATION; HISTOASPARTIC
PROTEASE; ANTIMALARIAL ACTIVITY
AB Plasmepsins (PMs) are pepsin-like aspartic proteases present in different species of parasite Plasmodium. Four Plasmodium spp. (P. vivax, P. ovale, P. malariae, and the most lethal P. falciparum) are mainly responsible for causing human malaria that affects millions worldwide. Due to the complexity and rate of parasite mutation coupled with regional variations, and the emergence of P. falciparum strains which are resistant to antimalarial agents such as chloroquine and sulfadoxine/pyrimethamine, there is constant pressure to find new and lasting chemotherapeutic drug therapies. Since many proteases represent therapeutic targets and PMs have been shown to play an important role in the survival of parasite, these enzymes have recently been identified as promising targets for the development of novel antimalarial drugs. The genome of P. falciparum encodes 10 PMs (PMI, PMII, PMIV-X and histo-aspartic protease (HAP)), 4 of which (PM!, PMII, PMIV and HAP) reside within the food vacuole, are directly involved in degradation of human hemoglobin, and share 50-79% amino acid sequence identity. This review focuses on structural studies of only these four enzymes, including their orthologs in other Plasmodium spp.. Almost all original crystallographic studies were performed with PMII, but more recent work on PMIV. PMI, and HAP resulted in a more complete picture of the structure-function relationship of vacuolar PMs. Many structures of inhibitor complexes of vacuolar plasmepsins, as well as their zymogens, have been reported in the last 15 years. Information gained by such studies will be helpful for the development of better inhibitors that could become a new class of potent antimalarial drugs. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome. Published by Elsevier B.V.
C1 [Bhaumik, Prasenjit; Gustchina, Alla; Wlodawer, Alexander] NCI, Prot Struct Sect, MCL, Frederick, MD 21702 USA.
RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, MCL, Bldg 536,Rm 5, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We are grateful to Professor Ben Dunn for constructive criticism of a
draft of this manuscript. This project was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 83
TC 14
Z9 14
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD JAN
PY 2012
VL 1824
IS 1
SI SI
BP 207
EP 223
DI 10.1016/j.bbapap.2011.04.008
PG 17
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 871CS
UT WOS:000298715900021
PM 21540129
ER
PT J
AU Kawamoto, EM
Gleichmann, M
Yshii, LM
Lima, LD
Mattson, MP
Scavone, C
AF Kawamoto, E. M.
Gleichmann, M.
Yshii, L. M.
de Sa Lima, L.
Mattson, M. P.
Scavone, C.
TI Effect of activation of canonical Wnt signaling by the Wnt-3a protein on
the susceptibility of PC12 cells to oxidative and apoptotic insults
SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
LA English
DT Article
DE Wnt-3a; PC12 cells; Beta-catenin; NF-kappa B
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; FACTOR-KAPPA-B; HIPPOCAMPAL-NEURONS;
CYTO-TOXICITY; BETA-CATENIN; PATHWAY; DISEASE; EXPRESSION; KINASE; GENES
AB Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid beta-peptide (A beta(25-35); 50 mu M). Cells (1 x 10(6) cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of beta-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer's and Huntington's diseases.
C1 [Kawamoto, E. M.; Yshii, L. M.; de Sa Lima, L.; Scavone, C.] Univ Sao Paulo, Dept Farmacol, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil.
[Kawamoto, E. M.; Gleichmann, M.; Mattson, M. P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Scavone, C (reprint author), Univ Sao Paulo, Dept Farmacol, Inst Ciencias Biomed, Ave Lineu Prestes 1524, BR-05508900 Sao Paulo, Brazil.
EM cristoforo.scavone@gmail.com
RI Mattson, Mark/F-6038-2012; Kawamoto, Elisa/E-3485-2012; YSHII,
Lidia/I-6039-2013;
OI Kawamoto, Elisa/0000-0001-8637-414X; YSHII, Lidia/0000-0002-1988-6855;
Scavone, Cristoforo/0000-0002-1206-0882
FU FAPESP [06/59722-1]; CNPq [0668-05-2]; CAPES; Sumitomo Bank; National
Institute on Aging of the NIH
FX We thank Maria Aparecida G.S. Fernandes for technical assistance.
Research supported by FAPESP (#06/59722-1 to C. Scavone), CNPq
(#0668-05-2), CAPES, Bunka Fund - Sumitomo Bank, and the National
Institute on Aging Intramural Research Program of the NIH. E.M. Kawamoto
and C. Scavone were recipients of fellowships from FAPESP and CNPq,
respectively.
NR 40
TC 10
Z9 10
U1 1
U2 14
PU ASSOC BRAS DIVULG CIENTIFICA
PI SAO PAULO
PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, 00, BRAZIL
SN 0100-879X
J9 BRAZ J MED BIOL RES
JI Brazilian J. Med. Biol. Res.
PD JAN
PY 2012
VL 45
IS 1
BP 58
EP 67
DI 10.1590/S0100-879X2011007500157
PG 10
WC Biology; Medicine, Research & Experimental
SC Life Sciences & Biomedicine - Other Topics; Research & Experimental
Medicine
GA 875RU
UT WOS:000299053200010
PM 22124704
ER
PT J
AU Marcus, L
Murphy, R
Fox, E
McCully, C
Cruz, R
Warren, KE
Meyer, T
McNiff, E
Balis, FM
Widemann, BC
AF Marcus, Leigh
Murphy, Robert
Fox, Elizabeth
McCully, Cynthia
Cruz, Raphael
Warren, Katherine E.
Meyer, Thorsten
McNiff, Edward
Balis, Frank M.
Widemann, Brigitte C.
TI The plasma and cerebrospinal fluid pharmacokinetics of the platinum
analog satraplatin after intravenous administration in non-human
primates
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Pharmocology; Non-human primate; Satraplatin; Pharmacokinetics
ID HIGH-GRADE ASTROCYTOMA; CELL LUNG-CANCER; PHASE-I; ACQUIRED-RESISTANCE;
RHESUS-MONKEY; CISPLATIN; CHILDREN; OXALIPLATIN; CARBOPLATIN;
CHEMOTHERAPY
AB Satraplatin is an orally bioavailable platinum analog with preclinical activity in cisplatin resistant models and clinical activity in adults with refractory cancers. The cerebrospinal fluid (CSF) penetration of cisplatin and carboplatin in non-human primates (NHP) is limited (3.7 and 2.6%, respectively). We evaluated the plasma and CSF pharmacokinetics (PK) of satraplatin after an intravenous (IV) dose in NHP.
Satraplatin (120 mg/m(2)) was administered as 1 h IV infusion in DMSO (5%) and normal saline to 5 NHP. Serial blood and CSF samples were obtained over 48 h. Plasma ultrafiltrate (UF) was immediately prepared by centrifugation. Platinum was quantified in plasma UF and CSF using a validated atomic absorption spectroscopy assay with lower limit of quantification (LLQ) of 0.025 mu M in UF and 0.006 mu M after concentration in CSF. Pharmacokinetic parameters were estimated using non-compartmental analyses. CSF penetration was calculated from the CSF AUC(0-48h) : plasma UF AUC(0-48h).
Satraplatin was well tolerated. Median (range) PK parameters in plasma UF were: maximum concentration (C (max)) 8.3 mu M (5.7-10.6), area under the curve (AUC(0-48h)) 29.2 mu M h (22.6-33.2), clearance 0.36 l/h/kg (0.31-0.37), and t (1/2) 18.8 h (13.4-25). Satraplatin was detected in the CSF of all NHP. Median (range) PK parameters in CSF were: C (max) 0.07 mu M (0.02-0.12), AUC(0-48h) 1.2 mu M h (0.49-2.43). The median (range) CSF penetration of satraplatin was 4.3% (2.2-7.4).
Satraplatin penetration into CSF is similar to that of carboplatin and cisplatin, despite its greater lipophilicity. The development of a phase I trial of satraplatin for refractory childhood solid tumors including brain tumors is in progress.
C1 [Marcus, Leigh; Murphy, Robert; McCully, Cynthia; Cruz, Raphael; Warren, Katherine E.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Meyer, Thorsten; McNiff, Edward] Agennix, Munich, Germany.
[Meyer, Thorsten; McNiff, Edward] Agennix, Princeton, NJ USA.
RP Marcus, L (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5742, Bethesda, MD 20892 USA.
EM marculei@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 38
TC 2
Z9 2
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD JAN
PY 2012
VL 69
IS 1
BP 247
EP 252
DI 10.1007/s00280-011-1659-z
PG 6
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 870EO
UT WOS:000298652100028
PM 21706317
ER
PT J
AU Camargo, MC
Goto, Y
Zabaleta, J
Morgan, DR
Correa, P
Rabkin, CS
AF Camargo, M. Constanza
Goto, Yasuyuki
Zabaleta, Jovanny
Morgan, Douglas R.
Correa, Pelayo
Rabkin, Charles S.
TI Sex Hormones, Hormonal Interventions, and Gastric Cancer Risk: A
Meta-Analysis
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
ID HELICOBACTER-PYLORI INFECTION; ADJUVANT TAMOXIFEN THERAPY;
POPULATION-BASED COHORT; POSITIVE BREAST-CANCER; INS-GAS MICE;
REPRODUCTIVE FACTORS; REPLACEMENT THERAPY; 2ND CANCERS; POSTMENOPAUSAL
WOMEN; ORAL-CONTRACEPTIVES
AB Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen-and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR 0.74, 95% CI: 0.63-0.86) and HRT (RR = 0.77; 95% CI: 0.64-0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39-2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms. Cancer Epidemiol Biomarkers Prev; 21(1); 20-38. (C) 2011 AACR.
C1 [Camargo, M. Constanza] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Goto, Yasuyuki] Nagoya Univ, Grad Sch Med, Dept Prevent Med, Nagoya, Aichi 4648601, Japan.
[Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA.
[Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, Stanley S Scott Canc Ctr, New Orleans, LA USA.
[Morgan, Douglas R.] Univ N Carolina, Sch Med, Dept Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Correa, Pelayo] Vanderbilt Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37212 USA.
RP Camargo, MC (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-6116, Rockville, MD 20852 USA.
EM camargomc@mail.nih.gov
RI Camargo, M. Constanza/R-9891-2016
FU U.S. National Cancer Institute, NIH
FX This study was funded by the Intramural Research Program of the U.S.
National Cancer Institute, NIH.
NR 105
TC 53
Z9 58
U1 0
U2 3
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 JAN
PY 2012
VL 21
IS 1
BP 20
EP 38
DI 10.1158/1055-9965.EPI-11-0834
PG 19
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500002
PM 22028402
ER
PT J
AU Veiga, LHS
Bhatti, P
Ronckers, CM
Sigurdson, AJ
Stovall, M
Smith, SA
Weathers, R
Leisenring, W
Mertens, AC
Hammond, S
Neglia, JP
Meadows, AT
Donaldson, SS
Sklar, CA
Friedman, DL
Robison, LL
Inskip, PD
AF Veiga, Lene H. S.
Bhatti, Parveen
Ronckers, Cecile M.
Sigurdson, Alice J.
Stovall, Marilyn
Smith, Susan A.
Weathers, Rita
Leisenring, Wendy
Mertens, Ann C.
Hammond, Sue
Neglia, Joseph P.
Meadows, Anna T.
Donaldson, Sarah S.
Sklar, Charles A.
Friedman, Debra L.
Robison, Leslie L.
Inskip, Peter D.
TI Chemotherapy and Thyroid Cancer Risk: a Report from the Childhood Cancer
Survivor Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID 2ND MALIGNANT NEOPLASMS; ALKYLATING-AGENTS; SOLID TUMORS; RADIATION;
RADIOTHERAPY; EXPERIENCE; LEUKEMIA; THERAPY; DISEASE; COHORT
AB Background: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.
Methods: The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.
Results: Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.
Conclusions: Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.
Impact: Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy. Cancer Epidemiol Biomarkers Prev; 21(1); 92-101. (C) 2011 AACR.
C1 [Veiga, Lene H. S.; Bhatti, Parveen; Ronckers, Cecile M.; Sigurdson, Alice J.; Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Inst Radiat Protect & Dosimetry, Rio De Janeiro, Brazil.
[Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA.
[Ronckers, Cecile M.] Dutch Childhood Oncol Grp, Late Effects Childhood Canc Registry LATER, The Hague, Netherlands.
[Stovall, Marilyn; Smith, Susan A.; Weathers, Rita] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Mertens, Ann C.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Hammond, Sue] Childrens Hosp, Dept Lab Med & Pathol, Columbus, OH 43205 USA.
[Hammond, Sue] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Neglia, Joseph P.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA.
[Meadows, Anna T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Donaldson, Sarah S.] Stanford Canc Ctr, Dept Radiat Oncol, Stanford, CA USA.
[Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Canc Control & Prevent Program, Nashville, TN USA.
[Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
RP Veiga, LHS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7051,MSC 7238, Bethesda, MD 20892 USA.
EM veigal@mail.nih.gov
FU Department of Health and Human Services [5U01-CA-55727]; Lance Armstrong
Foundation [147149]
FX This work was supported by the Department of Health and Human Services
(grant number 5U01-CA-55727) to L.L. Robison. Additional support was
provided by the American Lebanese-Syrian Associated Charities (ALSAC),
the Lance Armstrong Foundation (grant number 147149), and the Intramural
Research Program of the National Cancer Institute, NIH.
NR 27
TC 37
Z9 37
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 JAN
PY 2012
VL 21
IS 1
BP 92
EP 101
DI 10.1158/1055-9965.EPI-11-0576
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500010
PM 22028399
ER
PT J
AU Mavaddat, N
Barrowdale, D
Andrulis, IL
Domchek, SM
Eccles, D
Nevanlinna, H
Ramus, SJ
Spurdle, A
Robson, M
Sherman, M
Mulligan, AM
Couch, FJ
Engel, C
McGuffog, L
Healey, S
Sinilnikova, OM
Southey, MC
Terry, MB
Goldgar, D
O'Malley, F
John, EM
Janavicius, R
Tihomirova, L
Hansen, TVO
Nielsen, FC
Osorio, A
Stavropoulou, A
Benitez, J
Manoukian, S
Peissel, B
Barile, M
Volorio, S
Pasini, B
Dolcetti, R
Putignano, AL
Ottini, L
Radice, P
Hamann, U
Rashid, MU
Hogervorst, FB
Kriege, M
van der Luijt, RB
Peock, S
Frost, D
Evans, DG
Brewer, C
Walker, L
Rogers, MT
Side, LE
Houghton, C
Weaver, J
Godwin, AK
Schmutzler, RK
Wappenschmidt, B
Meindl, A
Kast, K
Arnold, N
Niederacher, D
Sutter, C
Deissler, H
Gadzicki, D
Preisler-Adams, S
Varon-Mateeva, R
Schonbuchner, I
Gevensleben, H
Stoppa-Lyonnet, D
Belotti, M
Barjhoux, L
Isaacs, C
Peshkin, BN
Caldes, T
de la Hoya, M
Canadas, C
Heikkinen, T
Heikkila, P
Aittomaki, K
Blanco, I
Lazaro, C
Brunet, J
Agnarsson, BA
Arason, A
Barkardottir, RB
Dumont, M
Simard, J
Montagna, M
Agata, S
D'Andrea, E
Yan, M
Fox, S
Rebbeck, TR
Rubinstein, W
Tung, N
Garber, JE
Wang, XS
Fredericksen, Z
Pankratz, VS
Lindor, NM
Szabo, C
Offit, K
Sakr, R
Gaudet, MM
Singer, CF
Tea, MK
Rappaport, C
Mai, PL
Greene, MH
Sokolenko, A
Imyanitov, E
Toland, AE
Senter, L
Sweet, K
Thomassen, M
Gerdes, AM
Kruse, T
Caligo, M
Aretini, P
Rantala, J
von Wachenfeld, A
Henriksson, K
Steele, L
Neuhausen, SL
Nussbaum, R
Beattie, M
Odunsi, K
Sucheston, L
Gayther, SA
Nathanson, K
Gross, J
Walsh, C
Karlan, B
Chenevix-Trench, G
Easton, DF
Antoniou, AC
AF Mavaddat, Nasim
Barrowdale, Daniel
Andrulis, Irene L.
Domchek, Susan M.
Eccles, Diana
Nevanlinna, Heli
Ramus, Susan J.
Spurdle, Amanda
Robson, Mark
Sherman, Mark
Mulligan, Anna Marie
Couch, Fergus J.
Engel, Christoph
McGuffog, Lesley
Healey, Sue
Sinilnikova, Olga M.
Southey, Melissa C.
Terry, Mary Beth
Goldgar, David
O'Malley, Frances
John, Esther M.
Janavicius, Ramunas
Tihomirova, Laima
Hansen, Thomas V. O.
Nielsen, Finn C.
Osorio, Ana
Stavropoulou, Alexandra
Benitez, Javier
Manoukian, Siranoush
Peissel, Bernard
Barile, Monica
Volorio, Sara
Pasini, Barbara
Dolcetti, Riccardo
Putignano, Anna Laura
Ottini, Laura
Radice, Paolo
Hamann, Ute
Rashid, Muhammad U.
Hogervorst, Frans B.
Kriege, Mieke
van der Luijt, Rob B.
Peock, Susan
Frost, Debra
Evans, D. Gareth
Brewer, Carole
Walker, Lisa
Rogers, Mark T.
Side, Lucy E.
Houghton, Catherine
Weaver, JoEllen
Godwin, Andrew K.
Schmutzler, Rita K.
Wappenschmidt, Barbara
Meindl, Alfons
Kast, Karin
Arnold, Norbert
Niederacher, Dieter
Sutter, Christian
Deissler, Helmut
Gadzicki, Doroteha
Preisler-Adams, Sabine
Varon-Mateeva, Raymonda
Schoenbuchner, Ines
Gevensleben, Heidrun
Stoppa-Lyonnet, Dominique
Belotti, Muriel
Barjhoux, Laure
Isaacs, Claudine
Peshkin, Beth N.
Caldes, Trinidad
de la Hoya, Miguel
Canadas, Carmen
Heikkinen, Tuomas
Heikkila, Paivi
Aittomaki, Kristiina
Blanco, Ignacio
Lazaro, Conxi
Brunet, Joan
Agnarsson, Bjarni A.
Arason, Adalgeir
Barkardottir, Rosa B.
Dumont, Martine
Simard, Jacques
Montagna, Marco
Agata, Simona
D'Andrea, Emma
Yan, Max
Fox, Stephen
Rebbeck, Timothy R.
Rubinstein, Wendy
Tung, Nadine
Garber, Judy E.
Wang, Xianshu
Fredericksen, Zachary
Pankratz, Vernon S.
Lindor, Noralane M.
Szabo, Csilla
Offit, Kenneth
Sakr, Rita
Gaudet, Mia M.
Singer, Christian F.
Tea, Muy-Kheng
Rappaport, Christine
Mai, Phuong L.
Greene, Mark H.
Sokolenko, Anna
Imyanitov, Evgeny
Toland, Amanda Ewart
Senter, Leigha
Sweet, Kevin
Thomassen, Mads
Gerdes, Anne-Marie
Kruse, Torben
Caligo, Maria
Aretini, Paolo
Rantala, Johanna
von Wachenfeld, Anna
Henriksson, Karin
Steele, Linda
Neuhausen, Susan L.
Nussbaum, Robert
Beattie, Mary
Odunsi, Kunle
Sucheston, Lara
Gayther, Simon A.
Nathanson, Kate
Gross, Jenny
Walsh, Christine
Karlan, Beth
Chenevix-Trench, Georgia
Easton, Douglas F.
Antoniou, Antonis C.
CA HEBON
EMBRACE
GEMO Study Collaborators
kConFab Investigators
SWE-BRCA Collaborators
Consortium Investigators Modifiers
TI Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation
Carriers: Results from the Consortium of Investigators of Modifiers of
BRCA1/2 (CIMBA)
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ESTROGEN-RECEPTOR STATUS; IMMUNOHISTOCHEMICAL MARKERS; GERMLINE
MUTATIONS; TUMOR SUBTYPES; FEATURES; RISK; PHENOTYPE; WOMEN; PREDICTION;
CARCINOMA
AB Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization.
Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers.
Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 x 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend 6.8 x 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 x 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 x 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 x 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%).
Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134-47. (C) 2011 AACR.
C1 [Mavaddat, Nasim; Barrowdale, Daniel; McGuffog, Lesley; Peock, Susan; Frost, Debra; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Andrulis, Irene L.; O'Malley, Frances] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada.
[Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA.
[Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA.
[Robson, Mark; Offit, Kenneth; Sakr, Rita] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY USA.
[Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Andrulis, Irene L.; O'Malley, Frances] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Rebbeck, Timothy R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Weaver, JoEllen] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, NHS Trust, Southampton SO9 5NH, Hants, England.
[Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Gross, Jenny; Walsh, Christine; Karlan, Beth] Cedars Sinai Med Ctr, Samuel Oschin Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Gross, Jenny; Walsh, Christine; Karlan, Beth] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Los Angeles, CA 90048 USA.
[Spurdle, Amanda; Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Sherman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA.
[Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Couch, Fergus J.; Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
[Sinilnikova, Olga M.] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France.
[Sinilnikova, Olga M.; Barjhoux, Laure] Univ Lyon 1, Canc Res Ctr Lyon, CNRS, INSERM,U1052,UMR5286, F-69622 Villeurbanne, France.
[GEMO Study Collaborators] Federat Natl Ctr Lutte Canc, Canc Genet Network Grp Genet & Canc, Lyon, France.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[Fox, Stephen; kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
[Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Dept Mol & Regenerat Med, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
[Gerdes, Anne-Marie] Univ Copenhagen, Rigshosp, Dept Clin Genet, DK-1168 Copenhagen, Denmark.
[Caldes, Trinidad; de la Hoya, Miguel; Canadas, Carmen] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Stavropoulou, Alexandra] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens, Greece.
[Manoukian, Siranoush; Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, San Giovanni Rotondo, Italy.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, San Giovanni Rotondo, Italy.
[Volorio, Sara; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy.
[Dolcetti, Riccardo] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, PN, Italy.
[Putignano, Anna Laura] Univ Florence, Dept Clin Physiopathol, I-50121 Florence, Italy.
[Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy.
[Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, Heidelberg, Germany.
[Rashid, Muhammad U.] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan.
[Hogervorst, Frans B.] Family Canc Clin, Amsterdam, Netherlands.
[HEBON] Netherlands Canc Inst, Amsterdam, Netherlands.
[Kriege, Mieke] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England.
[Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales.
[Side, Lucy E.] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London WC1N 3JH, England.
[Houghton, Catherine] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, Div Tumor Genet, D-8000 Munich, Germany.
[Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany.
[Arnold, Norbert] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dept Obstet & Gynaecol, Univ Hosp Dusseldorf, D-40225 Dusseldorf, Germany.
[Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Gadzicki, Doroteha] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany.
[Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany.
[Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Campus Virchov Klinikum, Berlin, Germany.
Univ Wurzburg, Dept Med Genet, Inst Human Genet, Ctr Familial Breast & Ovarian Canc, Wurzburg, Germany.
[Stoppa-Lyonnet, Dominique; Belotti, Muriel] Inst Curie, Serv Genet Oncol, F-75231 Paris, France.
[Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, Unite U830, F-75231 Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France.
[Isaacs, Claudine; Peshkin, Beth N.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
Germans Trias & Pujol Biopmed Res Inst IGTP, Inst Catala Oncol, Hereditary Canc Program, Badalona, Spain.
[Blanco, Ignacio; Lazaro, Conxi] Hosp Duran i Reynals, Inst Catala Oncol, Hereditary Canc Program, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain.
[Brunet, Joan] Hosp Josp Trueta, Inst Catala Oncol, Hereditary Canc Program, Girona Biomed Res Inst IdiBGi, Girona, Spain.
[Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.] Univ Iceland, Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada.
[Simard, Jacques] Univ Laval, Quebec City, PQ, Canada.
[Montagna, Marco; Agata, Simona] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy.
[D'Andrea, Emma] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy.
[Yan, Max] Prince Wales Hosp, Dept Anat Pathol, Randwick, NSW 2031, Australia.
[Rubinstein, Wendy] N Shore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Szabo, Csilla] Univ Delaware, Newark, DE USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine] Med Univ Vienna, Dept OB GYN, Vienna, Austria.
[Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria.
[Sokolenko, Anna; Imyanitov, Evgeny] St Petersburg Pediat Med Acad, Mol Oncol Lab, NN Petrov Inst Oncol, St Petersburg, Russia.
[Sokolenko, Anna; Imyanitov, Evgeny] St Petersburg Pediat Med Acad, Dept Med Genet, St Petersburg, Russia.
[Toland, Amanda Ewart] Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Senter, Leigha; Sweet, Kevin] Ohio State Univ, Med Ctr, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Thomassen, Mads; Kruse, Torben] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Caligo, Maria; Aretini, Paolo] Univ Pisa, Sect Genet Oncol, Dept Lab Med, Pisa, Italy.
[Caligo, Maria; Aretini, Paolo] Univ Hosp Pisa, Pisa, Italy.
[Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[von Wachenfeld, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[SWE-BRCA Collaborators] Karolinska Univ, Stockholm, Sweden.
[Henriksson, Karin] Univ Lund Hosp, Ctr Oncol, S-22185 Lund, Sweden.
[Steele, Linda; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
[Nussbaum, Robert] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA.
[Beattie, Mary] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Beattie, Mary] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
RP Antoniou, AC (reprint author), Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
EM antonis@srl.cam.ac.uk
RI Oosterwijk, Jan C./G-5770-2011; Lester, Jenny/B-5933-2012; Toland,
Amanda/E-4202-2011; Arnold, Norbert/E-3012-2010; Osorio,
Ana/I-4324-2014; GLADIEFF, Laurence/O-5129-2014; Dolcetti,
Riccardo/O-3832-2015; montagna, marco/E-2225-2012; D'Andrea,
Emma/B-4374-2013; Sweet, Kevin/E-4172-2011; Andrulis, Irene/E-7267-2013;
Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Spurdle,
Amanda/A-4978-2011; Ligtenberg, Marjolijn/N-9666-2013; Sokolenko,
Anna/G-3123-2013; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017;
OI Arnold, Norbert/0000-0003-4523-8808; Osorio, Ana/0000-0001-8124-3984;
GLADIEFF, Laurence/0000-0002-6980-9719; Dolcetti,
Riccardo/0000-0003-1625-9853; montagna, marco/0000-0002-4929-2150;
Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798;
Spurdle, Amanda/0000-0003-1337-7897; Barrowdale,
Daniel/0000-0003-1661-3939; PUTIGNANO, Anna Laura/0000-0001-9434-1612;
Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976;
Fox, Stephen/0000-0002-7648-8896; Ligtenberg,
Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562;
Peissel, Bernard/0000-0001-9233-3571; Janavicius,
Ramunas/0000-0002-3773-8485; Rappaport-Fuerhauser,
Christine/0000-0002-6820-0020; Robson, Mark/0000-0002-3109-1692; Eeles,
Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901;
Jacobs, Chris/0000-0002-9557-9080; Evans, Gareth/0000-0002-8482-5784
FU University of Kansas Cancer Center; Kansas Bioscience Authority Eminent
Scholar Program; Cancer Research UK [C12292/A11174, C1287/A10118,
C1287/A11990, C5047/A8385]; European Community [223175,
HEALTH-F2-2009-223175]; Medical Research Council; National Cancer
Institute, NIH, [RFA-CA-06-503]; Breast Cancer Family Registry and
Principal Investigators, including Cancer Care Ontario [U01 CA69467];
Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01
CA69631]; Huntsman Cancer Institute [U01 CA69446]; Cancer Prevention
Institute of California [U01 CA69417]; University of Melbourne [U01
CA69638]; Research Triangle Institute Informatics Support Center (RFP)
[N02PC45022-46]; Cancer Care Ontario; U.S. National Cancer Institute,
NIH under RFA [CA-06-503]; Research Council of Lithuania [LIG-19/2010];
LSC [05.0023.04., 10.0010.08]; NEYE Foundation; Fundacion Mutua
Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of
Science and Innovation [FIS PI08 1120]; Basque Foundation for Health
Innovation and Research (BIOEF) [BIO07/CA/006]; DKFZ; Dutch Cancer
Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024];
NIHR; Royal Marsden NHS Foundation Trust; Eileen Stein Jacoby Fund
[U01CA69631, 5U01CA113916]; Centre of Molecular Medicine Cologne (CMMC)
[109076]; Ligue National Contre le Cancer and The Association; National
Cancer Institute [NCI P30 CA51008-12]; Fisher Center for Familial Cancer
Research; Helsinki University Central Hospital; Academy of Finland
[132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Icelandic
Association "Walking for Breast Cancer Research"; Landspitali University
Hospital; Canadian Breast Cancer Research [019511]; Ministero della
Salute [RFPS 2006-5-341353, ACC2/R6.9]; Progetto Tumori Femminili;
National Breast Cancer Foundation; National Health and Medical Research
Council (NHMRC) [145684, 288704, 454508]; Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia;
Cancer Foundation of Western Australia; NIH [CA116167, CA128978,
CA74415]; Specialized Program of Research Excellence (SPORE) in Breast
Cancer [CA116201]; Komen Foundation for the Cure; Breast Cancer Research
Foundation; U.S. National Cancer Institute; Westat, Inc.
[NO2-CP-11019-50, N02-CP-65504]; Russian Federation for Basic Research
[10-04-92601, 11-04-00250, 11-04-00227]; Federal Agency for Science and
Innovations [02.740.11.0780]; Commission of the European Communities
[PITN-GA-2009-238132]; OSU Comprehensive Cancer Center; ITT (Tuscany
Institute for Tumors) [2010-2012]; NCI Bay Area Breast Cancer SPORE
[P50-CA058207]; Avon Foundation; UCSF Helen Diller Family Comprehensive
Cancer Center; CRUK; Cancer Genetics Network and Marjorie Cohen
Foundation; American Cancer Society [SIOP-06-258-01-CCE]
FX The author, A.K. Godwin, thanks the support from The University of
Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar
Program. A.K. Godwin is the Chancellors Distinguished Chair in
Biomedical Sciences-endowed Professor.; This work was supported by
Cancer Research UK grants C12292/A11174 and C1287/A10118. The research
leading to these results has received funding from the European
Community's Seventh Framework Programme under grant agreement no 223175
(HEALTH-F2-2009-223175). NM was funded by a scholarship from the Medical
Research Council. ACA is a CR-UK Senior Cancer Research Fellow. DFE is a
CR-UK Principal Research Fellow.; This work was supported by the
National Cancer Institute, NIH, under RFA-CA-06-503 and through
cooperative agreements with members of the Breast Cancer Family Registry
and Principal Investigators, including Cancer Care Ontario (U01
CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center
(U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer
Prevention Institute of California (U01 CA69417), University of
Melbourne (U01 CA69638), and Research Triangle Institute Informatics
Support Center (RFP No. N02PC45022-46).; This work was supported by
Cancer Care Ontario and the U.S. National Cancer Institute, NIH, under
RFA # CA-06-503 and through cooperative agreements with members of the
Breast Cancer Family Registry (BCFR) and principal investigators.;
Lithuania: This work is financially supported by the Research Council of
Lithuania grant LIG-19/2010 to R. Janavicius.; Latvia: L. Tihomirova was
financially supported by LSC grants 05.0023.04. and 10.0010.08.; The
authors thank NEYE Foundation for financial support; This study was
partially supported financially by the Fundacion Mutua Madrilena,
Asociacion Espanola Contra el Cancer and the Spanish Ministry of Science
and Innovation (FIS PI08 1120). This was funded, in part, by the Basque
Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006.;
The DKFZ study was supported by the DKFZ.; The HEBON study is supported
by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, and
NKI2007-3756 and the ZonMW grant 91109024.; EMBRACE is financially
supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D.
G. Evans and F. Lalloo are financially supported by an NIHR grant to the
Biomedical Research Centre, Manchester, UK. The investigators at The
Institute of Cancer Research and The Royal Marsden NHS Foundation Trust
are financially supported by an NIHR grant to the Biomedical Research
Centre at the Institute of Cancer Research and the Royal Marsden NHS
Foundation Trust. R. Eeles, E. Bancroft, and L. D'Mello are also
financially supported by a Cancer Research UK grant C5047/A8385.; A.K.
Godwinwas funded by U01CA69631, 5U01CA113916, and the Eileen Stein
Jacoby Fund.; GC-HBOC is financially supported by a grant of the German
Cancer Aid (grant 109076) the Centre of Molecular Medicine Cologne
(CMMC).; This study was supported by The Ligue National Contre le Cancer
and The Association "Le cancer du sein, parlons-en!" Award.; C. Isaacs
and B.N. Peshkin are supported by National Cancer Institute Grant (NCI
P30 CA51008-12) and by the Fisher Center for Familial Cancer Research.;
The HEBCS study has been financially supported by the Helsinki
University Central Hospital Research Fund, Academy of Finland (132473),
the Finnish Cancer Society, and the Sigrid Juselius Foundation.; The
ILUH group was supported by the Icelandic Association "Walking for
Breast Cancer Research" and by the Landspitali University Hospital
Research Fund.; This work was supported by the Canadian Institutes of
Health Research for the "CIHR Team in Familial Risks of Breast Cancer"
program and by the Canadian Breast Cancer Research Alliance-grant
#019511.; This study was supported by "Ministero della Salute" (grant
numbers RFPS 2006-5-341353, ACC2/R6.9 and "Progetto Tumori Femminili").;
kConFab is supported by grants from the National Breast Cancer
Foundation, the National Health and Medical Research Council (NHMRC) and
by the Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, and the Cancer Foundation of
Western Australia (funded by NHMRC grants 145684, 288704, and 454508).;
The MAYO study was supported by NIH grants CA116167, CA128978, a
Specialized Program of Research Excellence (SPORE) in Breast Cancer
(CA116201), and awards from the Komen Foundation for the Cure and the
Breast Cancer Research Foundation.; The research of Drs. P. L. Mai and
M. H. Greene was supported by the Intramural Research Program of the
U.S. National Cancer Institute and by support services contracts
NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc.; This work has been
supported by the Russian Federation for Basic Research (grants
10-04-92601, 11-04-00250, 11-04-00227), the Federal Agency for Science
and Innovations (contract 02.740.11.0780), and the Commission of the
European Communities (grant PITN-GA-2009-238132).; This work was
supported by the OSU Comprehensive Cancer Center. Caroline Craven and
Michelle O'Connor were responsible for patient accrual and data
management.; M. Caligo was supported by an ITT (Tuscany Institute for
Tumors) grant 2010-2012.; S. L. Neuhausen was partially supported by NIH
CA74415 and the Morris and Horowitz Families Endowed Professorship.; The
grant funding was obtained from the NIH, NCI Bay Area Breast Cancer
SPORE (P50-CA058207), and the Avon Foundation. Support was also provided
from the UCSF Helen Diller Family Comprehensive Cancer Center.; UKFOCR
was supported by a project grant from CRUK to Paul Pharoah.; The funding
was obtained from Breast Cancer Research Foundation (to K.L. Nathanson);
and Cancer Genetics Network and Marjorie Cohen Foundation (to S.M.
Domchek).; WCRI acknowledges support from the American Cancer Society,
SIOP-06-258-01-CCE.
NR 47
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U1 6
U2 43
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 JAN
PY 2012
VL 21
IS 1
BP 134
EP 147
DI 10.1158/1055-9965.EPI-11-0775
PG 14
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500014
PM 22144499
ER
PT J
AU Simard, EP
Shiels, MS
Bhatia, K
Engels, EA
AF Simard, Edgar P.
Shiels, Meredith S.
Bhatia, Kishor
Engels, Eric A.
TI Long-term Cancer Risk among People Diagnosed with AIDS during Childhood
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-DISEASES SOCIETY; HIV MEDICINE
ASSOCIATION; INSTITUTES-OF-HEALTH; UNITED-STATES; OPPORTUNISTIC
INFECTIONS; CHILDREN; HIV/AIDS; TRENDS; HUMAN-HERPESVIRUS-8
AB Background: Highly active antiretroviral therapy (HAART) results in partial immune restoration for people with AIDS, but its impact on cancer risk among children is unknown.
Methods: Data from the U. S. HIV/AIDS Cancer Match Study were used to evaluate cancer risk for people diagnosed with AIDS as children (diagnosed with AIDS at ages 0-14 years, during 1980-2007, followed for up to 10 years; N = 5,850). We calculated standardized incidence ratios (SIR) to compare cancer risk to the general population. Poisson regression evaluated changes in cancer incidence between the pre-HAART (1980-1995) and HAART eras (1996-2007).
Results: There were 106 cancers observed with significantly elevated risks for the two major AIDS-defining cancers: Kaposi sarcoma [KS; N = 20, SIR 1,694; 95% confidence interval (CI), 986-2,712 and SIR 1,146; 95% CI, 236-3,349] during the pre-HAART and HAART eras, respectively, and non-Hodgkin lymphoma (NHL; N = 64, SIR 338; 95% CI, 242-458 and SIR = 116; 95% CI, 74-175). Incidence of both cancers declined 87% and 60%, respectively, in the HAART era (P < 0.05). Of non-AIDS-defining cancers, leiomyosarcoma risk (N = 9) was elevated during both time periods (SIR 863; 95% CI, 235-2,211 and SIR 533; 95% CI, 173-1,243).
Conclusion: People diagnosed with AIDS during childhood remain at elevated risk for KS, NHL, and leiomyosarcoma in the HAART era. Incidence of KS and NHL declined relative to widespread HAART use, but there was no change in the incidence of other cancers.
Impact: People diagnosed with AIDS during childhood remain at elevated risk for certain cancers. Continued monitoring is warranted as this immunosuppressed population ages into adulthood where cancer risks generally increase. Cancer Epidemiol Biomarkers Prev; 21(1); 148-54. (C) 2011 AACR.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Simard, Edgar P.] Amer Canc Soc, Surveillance Res Program, Atlanta, GA 30329 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA.
EM engelse@mail.nih.gov
FU National Cancer Institute
FX This study was funded by the Intramural Research Program of the National
Cancer Institute.
NR 37
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2012
VL 21
IS 1
BP 148
EP 154
DI 10.1158/1055-9965.EPI-11-0823
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500015
PM 22068287
ER
PT J
AU Schlichting, JA
Soliman, AS
Schairer, C
Banerjee, M
Rozek, LS
Schottenfeld, D
Harford, JB
Merajver, SD
AF Schlichting, Jennifer A.
Soliman, Amr S.
Schairer, Catherine
Banerjee, Mousumi
Rozek, Laura S.
Schottenfeld, David
Harford, Joe B.
Merajver, Sofia D.
TI Association of Inflammatory and Noninflammatory Breast Cancer with
Socioeconomic Characteristics in the Surveillance, Epidemiology, and End
Results Database, 2000-2007
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HORMONE-RECEPTOR STATUS; DIFFERENT HISTOPATHOLOGIC TYPES; CENSUS-BASED
METHODOLOGY; AGE-SPECIFIC INCIDENCE; UNITED-STATES; CARCINOMA INCIDENCE;
RISK-FACTORS; MOLECULAR DETERMINANTS; INCIDENCE RATES; RESULTS PROGRAM
AB Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive form of primary breast cancer. Little is known about the risk factors for IBC, specifically the association with socioeconomic position (SEP).
Methods: The association between breast cancer type (IBC vs. non-IBC) with county-level SEP in the Surveillance, Epidemiology, and End Results database for cases diagnosed from 2000 to 2007 was examined. County-level SEP characteristics included metropolitan versus non-metropolitan residence, percentage below the poverty level, percentage less than high-school graduate, and an index combining the poverty and high-school variables. IBC and non-IBC age-adjusted incidence rates were calculated, stratified on SEP and race/ethnicity. The odds of IBC versus non-IBC given a particular SEP characteristic, adjusting for age and race/ethnicity, was examined through fitting of hierarchical logistic regression models (HLM).
Results: Incidence rates for IBC generally increased as SEP decreased, whereas the opposite was found for non-IBC. HLM results showed that low SEP is associated with higher odds of IBC: highest (>= 20%) versus lowest (<10%) persons below the poverty level [OR (95% confidence interval, CI) 1.25 (1.09-1.43)]; highest (>28.76%) versus lowest (<= 15.99%) persons less than high-school graduate [OR (95% CI) = 1.25 (1.10-1.42)]; and low SEP as measured by poverty-high school index versus high SEP [OR (95% CI) = 1.26 (1.11-1.44)].
Conclusion: Overall breast cancer has been found to be positively associated with SEP, whereas in this analysis, IBC was associated with decreasing SEP.
Impact: Studies focused on understanding the disparity in IBC incidence, as well as interventions to eliminate these differences are needed. Cancer Epidemiol Biomarkers Prev; 21(1); 155-65. (C) 2011 AACR.
C1 [Schlichting, Jennifer A.; Soliman, Amr S.; Schottenfeld, David; Merajver, Sofia D.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Rozek, Laura S.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Schottenfeld, David; Merajver, Sofia D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Merajver, Sofia D.] Univ Michigan, Ctr Global Hlth, Ann Arbor, MI 48109 USA.
[Schairer, Catherine] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
NCI, Office Int Affairs, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Schlichting, JA (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
EM jschlic@umich.edu
FU University of Michigan [CA R25 112383]; Avon Foundation; Breast Cancer
Research Foundation; Debbie Strange-Browne Inflammatory Breast Cancer
Foundation
FX This work was supported by a Rackham Merit Fellowship (J.A. Schlichting)
from the University of Michigan and the Cancer Epidemiology Education in
Special Populations Program of the University of Michigan (CA R25
112383). Additional funding was received from the Avon Foundation (A.S.
Soliman and S.D. Merajver), the Breast Cancer Research Foundation (S.D.
Merajver), and the Debbie Strange-Browne Inflammatory Breast Cancer
Foundation (S.D. Merajver).
NR 82
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Z9 8
U1 1
U2 3
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 JAN
PY 2012
VL 21
IS 1
BP 155
EP 165
DI 10.1158/1055-9965.EPI-11-0833
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500016
PM 22028401
ER
PT J
AU Southard, EB
Roff, A
Fortugno, T
Richie, JP
Kaag, M
Chinchilli, VM
Virtamo, J
Albanes, D
Weinstein, S
Wilson, RT
AF Southard, Emily B.
Roff, Alanna
Fortugno, Tracey
Richie, John P., Jr.
Kaag, Matthew
Chinchilli, Vernon M.
Virtamo, Jarmo
Albanes, Demetrius
Weinstein, Stephanie
Wilson, Robin Taylor
TI Lead, Calcium Uptake, and Related Genetic Variants in Association with
Renal Cell Carcinoma Risk in a Cohort of Male Finnish Smokers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID AMINOLEVULINIC-ACID DEHYDRATASE; VITAMIN-D-RECEPTOR; ACTIVE CA2+
REABSORPTION; BLOOD LEAD; 25-HYDROXYVITAMIN D; D SUPPLEMENTATION;
TARGETED THERAPY; UNITED-STATES; KIDNEY CANCER; NHANES-III
AB Background: Lead is classified as a probable human carcinogen. However, its role in renal cell cancer (RCC) has not been established. Calcium and vitamin D may off-set toxicity in vivo.
Methods: In this nested case-control study, whole blood lead, total serum calcium, and serum 25-hydroxyvitamin D levels were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Single-nucleotide polymorphisms (SNP) in five genes (CALB1, TRPV5, TRPV6, VDR, and ALAD) related to lead toxicity or calcium transport were genotyped. Logistic and linear regressions were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors.
Results: Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead [OR = 2.0; 95% confidence interval (CI), 1.0-3.9; quartile 4 (Q4) vs. Q1, P-trend = 0.022] and CALB1 rs1800645 (P-trend = 0.025, minor 'T' allele frequency = 0.34). Higher total serum calcium (P-trend <= 0.001) was associated with reduced RCC risk. Total serum calcium and 25-hydroxyvitamin D levels did not alter the association observed with lead. Time from enrollment to RCC diagnosis was positively associated with serum calcium (P-trend = 0.002) and 25-hydroxyvitamin D (P-trend = 0.054) among cases.
Conclusions: Higher blood lead concentrations, below the 10 mu g/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism.
Impact: Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated. Cancer Epidemiol Biomarkers Prev; 21(1); 191-201. (C) 2011 AACR.
C1 [Southard, Emily B.; Roff, Alanna; Fortugno, Tracey; Richie, John P., Jr.; Chinchilli, Vernon M.; Wilson, Robin Taylor] Penn State Univ, Dept Publ Hlth Sci, Div Urol, Coll Med, Hershey, PA USA.
[Kaag, Matthew] Penn State Univ, Dept Surg, Div Urol, Coll Med, Hershey, PA USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland.
[Albanes, Demetrius; Weinstein, Stephanie] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Wilson, RT (reprint author), Penn State Coll Med, Dept Publ Hlth Sci, Div Epidemiol, Penn State Canc Inst, 500 Univ Dr,Mail Code CH69, Hershey, PA 17033 USA.
EM rwilson@psu.edu
RI Albanes, Demetrius/B-9749-2015
FU American Institute for Cancer Research [200810]
FX The study was supported by American Institute for Cancer Research, grant
no. 200810 awarded to R.T. Wilson.
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2012
VL 21
IS 1
BP 191
EP 201
DI 10.1158/1055-9965.EPI-11-0670
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500020
PM 22086884
ER
PT J
AU Lindstrom, S
Schumacher, FR
Campa, D
Albanes, D
Andriole, G
Berndt, SI
Bueno-de-Mesquita, HB
Chanock, SJ
Diver, WR
Ganziano, JM
Gapstur, SM
Giovannucci, E
Haiman, CA
Henderson, B
Hunter, DJ
Johansson, M
Kolonel, LN
Le Marchand, L
Ma, J
Stampfer, M
Stevens, VL
Trichopoulos, D
Virtamo, J
Willett, WC
Yeager, M
Hsing, AW
Kraft, P
AF Lindstroem, Sara
Schumacher, Fredrick R.
Campa, Daniele
Albanes, Demetrius
Andriole, Gerald
Berndt, Sonja I.
Bueno-de-Mesquita, H. Bas
Chanock, Stephen J.
Diver, W. Ryan
Ganziano, J. Michael
Gapstur, Susan M.
Giovannucci, Edward
Haiman, Christopher A.
Henderson, Brian
Hunter, David J.
Johansson, Mattias
Kolonel, Laurence N.
Le Marchand, Loic
Ma, Jing
Stampfer, Meir
Stevens, Victoria L.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Willett, Walter C.
Yeager, Meredith
Hsing, Ann W.
Kraft, Peter
TI Replication of Five Prostate Cancer Loci Identified in an Asian
Population-Results from the NCI Breast and Prostate Cancer Cohort
Consortium (BPC3)
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GROWTH-FACTOR-I; GENOME-WIDE ASSOCIATION; BINDING PROTEIN-3; PREDICTORS;
GENES; RISK; MEN
AB Background: A recent genome-wide association study (GWAS) of prostate cancer in a Japanese population identified five novel regions not previously discovered in other ethnicities. In this study, we attempt to replicate these five loci in a series of nested prostate cancer case-control studies of European ancestry.
Methods: We genotyped five single-nucleotide polymorphism (SNP): rs13385191 (chromosome 2p24), rs12653946 (5p15), rs1983891 (6p21), rs339331 (6p22), and rs9600079 (13q22), in 7,956 prostate cancer cases and 8,148 controls from a series of nested case-control studies within the National cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We tested each SNP for association with prostate cancer risk and assessed whether associations differed with respect to disease severity and age of onset.
Results: Four SNPs (rs13385191, rs12653946, rs1983891, and rs339331) were significantly associated with prostate cancer risk (P values ranging from 0.01 to 1.1 x 10(-5)). Allele frequencies and ORs were overall lower in our population of European descent than in the discovery Asian population. SNP rs13385191 (C2orf43) was only associated with low-stage disease (P = 0.009, case-only test). No other SNP showed association with disease severity or age of onset. We did not replicate the 13q22 SNP, rs9600079 (P = 0.62).
Conclusions: Four SNPs associated with prostate cancer risk in an Asian population are also associated with prostate cancer risk in men of European descent.
Impact: This study illustrates the importance of evaluation of prostate cancer risk markers across ethnic groups. Cancer Epidemiol Biomarkers Prev; 21(1); 212-16. (C) 2011 AACR.
C1 [Lindstroem, Sara; Hunter, David J.; Stampfer, Meir; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ganziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA.
[Ganziano, J. Michael] Boston Vet Affairs Healthcare Syst, GRECC, Boston, MA USA.
[Ganziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Hunter, David J.; Ma, Jing; Stampfer, Meir; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Haiman, Christopher A.; Henderson, Brian] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Yeager, Meredith; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Lindstrom, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 655 Huntington Ave,Bldg 2,Room 249B, Boston, MA 02115 USA.
EM slindstr@hsph.harvard.edu
RI Albanes, Demetrius/B-9749-2015; Campa, Daniele/K-1617-2016
OI Campa, Daniele/0000-0003-3220-9944
FU U.S. NIH, National Cancer Institute [U01-CA98233-07, U01-CA98710-06,
U01-CA98216-06, U01-CA98758-07]; NIH/National Cancer Institute, Division
of Cancer Epidemiology and Genetics
FX This work was supported by the U.S. NIH, National Cancer Institute
(cooperative agreements U01-CA98233-07 to D.J. Hunter, U01-CA98710-06 to
S.M. Gapstur, U01-CA98216-06 to Elio Riboli and Rudolf Kaaks, and
U01-CA98758-07 to B. Henderson, and Intramural Research Program of
NIH/National Cancer Institute, Division of Cancer Epidemiology and
Genetics).
NR 16
TC 16
Z9 17
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2012
VL 21
IS 1
BP 212
EP 216
DI 10.1158/1055-9965.EPI-11-0870-T
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500022
PM 22056501
ER
PT J
AU Meng, SS
Song, FJ
Chen, HL
Gao, X
Amos, CI
Lee, JE
Wei, QY
Qureshi, AA
Han, JL
AF Meng, Shasha
Song, Fengju
Chen, Honglei
Gao, Xiang
Amos, Christopher I.
Lee, Jeffrey E.
Wei, Qingyi
Qureshi, Abrar A.
Han, Jiali
TI No Association between Parkinson Disease Alleles and the Risk of
Melanoma
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SKIN-CANCER
AB Background: Recent data showed that melanoma was more common among patients with Parkinson disease than individuals without Parkinson disease and vice versa. It has been hypothesized that these two diseases may share common genetic and environmental risk factors.
Methods: We evaluated the association between single-nucleotide polymorphisms (SNP) selected on the basis of recent genome-wide association studies (GWAS) on Parkinson disease risk and the risk of melanoma using 2,297 melanoma cases and 6,651 controls.
Results: The Parkinson disease SNPrs156429 in the chromosome 7p15 region was nominally associated with melanoma risk with P value of 0.04, which was not significant after the Bonferroni correction for multiple comparisons. No association was observed between the remaining 31 Parkinson disease SNPs and the risk of melanoma. The genetic score based on the number of Parkinson disease risk allele was not associated with melanoma risk [ OR for the highest genetic score quartile (30-35) vs. the lowest (15-20), 1.13, 95% confidence interval (CI), 0.47-2.70].
Conclusion: The Parkinson disease SNPs identified in published GWAS do not seem to play an important role in melanoma development.
Impact: The Parkinson disease susceptibility loci discovered by GWAS contribute little to the observed epidemiologic association between the Parkinson disease and melanoma. Cancer Epidemiol Biomarkers Prev; 21(1); 243-5. (C)2011 AACR.
C1 [Meng, Shasha; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gao, Xiang] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA.
[Gao, Xiang; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Song, Fengju; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Amos, Christopher I.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Lee, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
RP Han, JL (reprint author), Brigham & Womens Hosp, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM jiali.han@channing.harvard.edu
OI Chen, Honglei/0000-0003-3446-7779
FU NIH [CA87969, CA49449, CA055075, CA093459, CA122838]; National Institute
of Environmental Health Sciences [Z01-ES-101986]
FX This work was supported by NIH CA87969, CA49449, CA055075, CA093459, and
CA122838. This study was also in part supported by the intramural
research program of the NIH, the National Institute of Environmental
Health Sciences (Z01-ES-101986).
NR 8
TC 12
Z9 12
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 JAN
PY 2012
VL 21
IS 1
BP 243
EP 245
DI 10.1158/1055-9965.EPI-11-0905
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500026
PM 22086882
ER
PT J
AU Albanes, D
Weinstein, SJ
Mondul, AM
Virtamo, J
AF Albanes, Demetrius
Weinstein, Stephanie J.
Mondul, Alison M.
Virtamo, Jarmo
TI Circulating Vitamin D and Risk of Prostate Cancer-Response
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
C1 [Albanes, Demetrius; Weinstein, Stephanie J.; Mondul, Alison M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20982 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20982 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015
NR 1
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 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2012
VL 21
IS 1
BP 247
EP 247
DI 10.1158/1055-9965.EPI-11-1003
PG 1
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500028
ER
PT J
AU Hock, JM
Nealley, A
Morrison, D
Farah, C
Hosgood, HD
Zahm, S
AF Hock, Janet M.
Nealley, Amelia
Morrison, Deborah
Farah, Christopher
Hosgood, H. Dean
Zahm, Sheila
TI Unmet Challenges in Cancer Disparities-Letter
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
C1 [Hock, Janet M.; Nealley, Amelia; Morrison, Deborah; Farah, Christopher] Maine Inst Human Genet & Hlth, Bangor, ME USA.
[Hosgood, H. Dean; Zahm, Sheila] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hock, JM (reprint author), Maine Inst Human Genet & Hlth, Bangor, ME USA.
EM jhock@emh.org
RI Zahm, Shelia/B-5025-2015;
OI Hock, Janet/0000-0001-8873-2545
FU Intramural NIH HHS [Z99 CA999999]
NR 4
TC 3
Z9 3
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2012
VL 21
IS 1
BP 248
EP 249
DI 10.1158/1055-9965.EPI-11-1039
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 875RH
UT WOS:000299051500029
PM 22144498
ER
PT J
AU Sahasrabuddhe, VV
Parham, GP
Mwanahamuntu, MH
Vermund, SH
AF Sahasrabuddhe, Vikrant V.
Parham, Groesbeck P.
Mwanahamuntu, Mulindi H.
Vermund, Sten H.
TI Cervical Cancer Prevention in Low- and Middle-Income Countries:
Feasible, Affordable, Essential
SO CANCER PREVENTION RESEARCH
LA English
DT Review
ID HIV-INFECTED WOMEN; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-PAPILLOMAVIRUS;
ANTIRETROVIRAL THERAPY; RANDOMIZED-TRIAL; HPV DETECTION; ZAMBIA; INDIA;
TREAT; CRYOTHERAPY
AB The annual worldwide burden of the preventable disease cervical cancer is more than 530,000 new cases and 275,000 deaths, with the majority occurring in low-and middle-income countries (LMIC), where cervical cancer screening and early treatment are uncommon. Widely used in high-income countries, Pap smear (cytology based) screening is expensive and challenging for implementation in LMICs, where lower-cost, effective alternatives such as visual inspection with acetic acid (VIA) and rapid human papillomavirus (HPV)-based screening tests offer promise for scaling up prevention services. Integrating HPV screening with VIA in "screen-and-treat-or-refer" programs offers the dual benefits of HPV screening to maximize detection and using VIA to triage for advanced lesions/cancer, as well as a pelvic exam to address other gynecologic issues. A major issue in LMICs is coinfection with human immunodeficiency virus (HIV) and HPV, which further increases the risk for cervical cancer and marks a population with perhaps the greatest need of cervical cancer prevention. Public-private partnerships to enhance the availability of cervical cancer prevention services within HIV/AIDS care delivery platforms through initiatives such as Pink Ribbon Red Ribbon present an historic opportunity to expand cervical cancer screening in LMICs. Cancer Prev Res; 5(1); 11-17. (C)2011 AACR.
C1 [Sahasrabuddhe, Vikrant V.; Vermund, Sten H.] Vanderbilt Univ, Vanderbilt Inst Global Hlth, Sch Med, Nashville, TN 37203 USA.
[Sahasrabuddhe, Vikrant V.; Vermund, Sten H.] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN 37203 USA.
[Sahasrabuddhe, Vikrant V.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Parham, Groesbeck P.] Univ Alabama Birmingham, Sch Med, Ctr Infect Dis Res Zambia, Birmingham, AL USA.
[Parham, Groesbeck P.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA.
[Parham, Groesbeck P.; Mwanahamuntu, Mulindi H.] Univ Teaching Hosp, Lusaka, Zambia.
[Parham, Groesbeck P.; Mwanahamuntu, Mulindi H.] Univ Zambia, Sch Med, Lusaka, Zambia.
RP Vermund, SH (reprint author), Vanderbilt Univ, Vanderbilt Inst Global Hlth, Sch Med, 2525 W End Ave,Suite 750, Nashville, TN 37203 USA.
EM sten.vermund@vanderbilt.edu
OI Vermund, Sten/0000-0001-7289-8698
FU FIC NIH HHS [D43 TW001035]; Intramural NIH HHS [Z01 CP010124-13, Z99
CA999999]; NCI NIH HHS [R21 CA113465]
NR 65
TC 30
Z9 30
U1 2
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JAN
PY 2012
VL 5
IS 1
BP 11
EP 17
DI 10.1158/1940-6207.CAPR-11-0540
PG 7
WC Oncology
SC Oncology
GA 877RT
UT WOS:000299200500003
PM 22158053
ER
PT J
AU Lowy, DR
Schiller, JT
AF Lowy, Douglas R.
Schiller, John T.
TI Reducing HPV-Associated Cancer Globally
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID INVASIVE CERVICAL-CANCER; HUMAN-PAPILLOMAVIRUS; PARTICLE VACCINE;
UNITED-STATES; PREVENTION; INFECTION; WOMEN; L1; IMPACT; ADOLESCENTS
AB Human papillomavirus (HPV)-related cancers are a major worldwide public health concern. Virtually all cervical cancer is HPV related, with 70% caused by HPV16 and -18. Variable proportions of certain noncervical cancers (e. g., anal, vulvar, and oropharyngeal) are HPV related; more than 90% of the HPV-related ones are caused by HPV16, -18. The HPV-related cancers are dominated by cervical cancer in the developing world, where cervical cancer screening is limited. In this setting, widespread uptake of current HPV vaccines by adolescent girls could reduce this cancer's incidence and mortality by approximately two-thirds, with cost-effective screening programs of adult women having the potential to reduce mortality more rapidly. In the industrialized world, some noncervical HPV-related cancers, especially oropharyngeal, are rapidly increasing, and now rival the incidence of cervical cancer, whose rates continue to decline thanks to established cervical screening programs. Therefore, reducing HPV-associated noncervical cancers with HPV vaccination has greater importance in the industrialized world, especially because there are no approved screening programs for these cancers. Preventing the substantial number of noncervical HPV cancers in men will require either "herd" immunity through high-vaccination rates in females or male vaccination. Current HPV vaccination can complement cervical screening in protecting against cervical cancer and may permit the safe reduction of screening intensity in industrialized countries. Second-generation HPV vaccines (active against a broader array of cervical cancer-related HPV types) could prevent an even higher proportion of cervical precancer and cancer and might permit further reductions in screening intensity. Cancer Prev Res; 5(1); 18-23. (C)2012 AACR.
C1 [Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4263,Bldg 37,Rm 4106, Bethesda, MD 20892 USA.
EM lowyd@mail.nih.gov
FU NIH, National Cancer Institute, and Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, and Center for Cancer Research.
NR 35
TC 57
Z9 61
U1 0
U2 10
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 JAN
PY 2012
VL 5
IS 1
BP 18
EP 23
DI 10.1158/1940-6207.CAPR-11-0542
PG 6
WC Oncology
SC Oncology
GA 877RT
UT WOS:000299200500004
PM 22219162
ER
PT J
AU Yuan, HY
Upadhyay, G
Yin, YZ
Kopelovich, L
Glazer, RI
AF Yuan, Hongyan
Upadhyay, Geeta
Yin, Yuzhi
Kopelovich, Levy
Glazer, Robert I.
TI Stem Cell Antigen-1 Deficiency Enhances the Chemopreventive Effect of
Peroxisome Proliferator-Activated Receptor gamma Activation
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID MEDIATES RADIATION-RESISTANCE; DMBA-INDUCED MAMMARY; PPAR-GAMMA;
BREAST-CANCER; PROGENITOR CELLS; GENETIC DISRUPTION; TUMOR-SUPPRESSOR;
TRANSGENIC MICE; SCA-1; EXPRESSION
AB Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPAR gamma and PTEN, and a reduction of pSer84PPAR gamma, pERK1/2, and PPAR delta. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPAR gamma agonist GW7845 and insensitivity to PPAR delta agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPAR gamma expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPAR gamma. Cancer Prev Res; 5(1); 51-60. (C)2011 AACR.
C1 [Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Glazer, Robert I.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Glazer, Robert I.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Kopelovich, Levy] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Glazer, RI (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
EM glazerr@georgetown.edu
FU NIH [1NO1 CN43302-WA19, 1G20RR025828-01]; National Cancer Institute, NIH
[P30CA051008]
FX The work was supported by NIH grant 1NO1 CN43302-WA19 (R. I. Glazer).
This study was supported by Award P30CA051008 from the National Cancer
Institute, NIH, and by Grant 1G20RR025828-01 from the NIH for Rodent
Barrier Facility Equipment.
NR 66
TC 5
Z9 6
U1 0
U2 1
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 JAN
PY 2012
VL 5
IS 1
BP 51
EP 60
DI 10.1158/1940-6207.CAPR-11-0256
PG 10
WC Oncology
SC Oncology
GA 877RT
UT WOS:000299200500009
PM 21955520
ER
PT J
AU Kim, EH
Deng, CX
Sporn, MB
Royce, DB
Risingsong, R
Williams, CR
Liby, KT
AF Kim, Eun-Hee
Deng, Chuxia
Sporn, Michael B.
Royce, Darlene B.
Risingsong, Renee
Williams, Charlotte R.
Liby, Karen T.
TI CDDO-Methyl Ester Delays Breast Cancer Development in Brca1-Mutated Mice
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID FATTY-ACID SYNTHASE; NITRIC-OXIDE PRODUCTION; ESTROGEN-RECEPTOR;
IRREVERSIBLE INHIBITOR; MAMMARY TUMORIGENESIS; TYROSINE KINASE;
TUMOR-FORMATION; PREVENTION; CHEMOPREVENTION; BRCA1
AB The breast cancer-associated gene 1 (BRCA1) is the most frequently mutated tumor suppressor gene in familial breast cancers. Mutations in BRCA1 also predispose to other types of cancers, pointing to a fundamental role of this pathway in tumor suppression and emphasizing the need for effective chemoprevention in these high-risk patients. Because the methyl ester of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) is a potent chemopreventive agent, we tested its efficacy in a highly relevant mouse model of BRCA1-mutated breast cancer. Beginning at 12 weeks of age, Brca1(Co/Co); MMTV-Cre;p53(+/-) mice were fed powdered control diet or diet containing CDDO-Me (50 mg/kg diet). CDDO-Me significantly (P < 0.05) delayed tumor development in the Brca1-mutated mice by an average of 5.2 weeks. We also observed that levels of ErbB2, p-ErbB2, and cyclin D1 increased in a time-dependent manner in the mammary glands in Brca1-deficient mice, and CDDO-Me inhibited the constitutive phosphorylation of ErbB2 in tumor tissues from these mice. In BRCA1-deficient cell lines, the triterpenoids directly interacted with ErbB2, decreased constitutive phosphorylation of ErbB2, inhibited proliferation, and induced G(0)-G(1) arrest. These results suggest that CDDO-Me has the potential to prevent BRCA1-mutated breast cancer. Cancer Prev Res; 5(1); 89-97. (C)2011 AACR.
C1 [Liby, Karen T.] Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA.
[Kim, Eun-Hee; Sporn, Michael B.; Royce, Darlene B.; Risingsong, Renee; Williams, Charlotte R.] Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03755 USA.
[Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
RP Liby, KT (reprint author), Dartmouth Med Sch, Dept Med, Remsen 524,HB 7650, Hanover, NH 03755 USA.
EM Karen.T.Liby@Dartmouth.Edu
RI deng, chuxia/N-6713-2016
FU Breast Cancer Research Foundation; NIH [RO1 CA78814]; Reata
Pharmaceuticals, Inc.
FX These studies were supported by the Breast Cancer Research Foundation
and the NIH (RO1 CA78814).; M. B. Sporn has commercial research grant in
Reata Pharmaceuticals, Inc.; M. B. Sporn and K. Liby have patent
interest in synthetic triterpenoids. No potential conflicts of interest
were disclosed by other authors.
NR 43
TC 22
Z9 23
U1 1
U2 1
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 JAN
PY 2012
VL 5
IS 1
BP 89
EP 97
DI 10.1158/1940-6207.CAPR-11-0359
PG 9
WC Oncology
SC Oncology
GA 877RT
UT WOS:000299200500013
PM 21933912
ER
PT J
AU Do, JS
Foucras, G
Kamada, N
Schenk, AF
Shaw, M
Nunez, G
Paul, WE
Min, B
AF Do, Jeong-su
Foucras, Gilles
Kamada, Nobuhiko
Schenk, Austin F.
Shaw, Michael
Nunez, Gabriel
Paul, William E.
Min, Booki
TI Both exogenous commensal and endogenous self antigens stimulate T cell
proliferation under lymphopenic conditions
SO CELLULAR IMMUNOLOGY
LA English
DT Article
DE Homeostasis; T cell; Commensal antigen; FTY720; Self antigen;
Lymphopenia
ID HOMEOSTATIC PROLIFERATION; IN-VIVO; AUTOIMMUNITY; SEQUESTRATION;
EXPRESSION; INDUCTION; SURVIVAL
AB Within lymphopenic recipients, naive T cells undergo proliferation that is induced by homeostatic mechanisms. Earlier studies have demonstrated that commensal antigens play a key role in inducing the proliferation. However, a relative contribution of endogenous self antigens in this process has not been formally investigated. In this study, we utilized a pharmacologic inhibitor that blocks T cell egress from the lymphoid tissues, antibiotics, and germ-free animals to examine the role of commensal and self antigens. The results suggest that T cell proliferation under lymphopenic conditions is a heterogeneous process triggered by both exogenous commensal and endogenous self antigens. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Do, Jeong-su; Schenk, Austin F.; Min, Booki] Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, Cleveland, OH 44195 USA.
[Foucras, Gilles; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Kamada, Nobuhiko; Shaw, Michael; Nunez, Gabriel] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Kamada, Nobuhiko; Shaw, Michael; Nunez, Gabriel] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Min, B (reprint author), Cleveland Clin Fdn, Dept Immunol NB30, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM minb@ccf.org
RI Do, Jeong su/G-9483-2014;
OI Kamada, Nobuhiko/0000-0002-1980-4178
FU NIH [A1074932]; NIAID/NIH
FX This study was supported by NIH grant A1074932 (B.M.) and the intramural
research program of the NIAID/NIH.
NR 28
TC 5
Z9 5
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0008-8749
J9 CELL IMMUNOL
JI Cell. Immunol.
PY 2012
VL 272
IS 2
BP 117
EP 123
DI 10.1016/j.cellimm.2011.11.002
PG 7
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 879AP
UT WOS:000299302400003
PM 22169530
ER
PT J
AU Tsourkas, PK
Liu, WL
Das, SC
Pierce, SK
Raychaudhuri, S
AF Tsourkas, Philippos K.
Liu, Wanli
Das, Somkanya C.
Pierce, Susan K.
Raychaudhuri, Subhadip
TI Discrimination of membrane antigen affinity by B cells requires
dominance of kinetic proofreading over serial engagement
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Article
DE computational modeling; Monte Carlo; lymphocyte signaling; Lyn; Syk
ID RESPONSES IN-VIVO; SYNAPSE FORMATION; LYMPH-NODE; SUBCAPSULAR SINUS;
DENDRITIC CELLS; LIVING CELLS; MONTE-CARLO; T-CELLS; ACTIVATION;
ADHESION
AB B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity, a process known as affinity discrimination. We use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial engagement. We find that if B-cell receptors become signaling-capable immediately upon antigen binding, which results in decreasing serial engagement as affinity increases, then increasing affinity can lead to weaker signaling. Rather, antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable, a process similar to kinetic proofreading. This process overcomes the loss in serial engagement due to increasing antigen affinity, and replicates the monotonic increase in B-cell signaling with increasing affinity that has been observed in B-cell activation experiments. This finding matches well with the experimentally observed time (similar to 20 s) required for the B-cell receptor signaling domains to undergo antigen and lipid raft-mediated conformational changes that lead to Src-family kinase recruitment. We hypothesize that the physical basis for a threshold time of antigen binding might lie in the formation timescale of B-cell receptor dimers. The time required for dimer formation decreases with increasing antigen affinity, thereby resulting in shorter threshold antigen binding times as affinity increases. Such an affinity-dependent kinetic proofreading requirement results in affinity discrimination very similar to that observed in biological experiments. B-cell affinity discrimination is critical to the process of affinity maturation and the production of high-affinity antibodies, and thus our results have important implications in applications such as vaccine design. Cellular & Molecular Immunology (2012) 9, 62-74; doi: 10.1038/cmi.2011.29; published online 12 September 2011
C1 [Tsourkas, Philippos K.; Das, Somkanya C.; Raychaudhuri, Subhadip] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Liu, Wanli; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Raychaudhuri, S (reprint author), Univ Calif Davis, Dept Biomed Engn, 1 Shields Ave, Davis, CA 95616 USA.
EM raychaudhuri@ucdavis.edu
RI liu, wanli/H-5690-2011; Tsourkas, Philippos/G-4026-2014;
OI liu, wanli/0000-0003-2624-6802; Raychaudhuri,
Subhadip/0000-0002-9873-6475
FU NIH [AI074022]
FX The authors thank Dr Emanual Maverakis, Dr Aaron Dinner and Dr Stephen
Kaattari for proofreading the manuscript and offering valuable advice.
PT and SR are supported by NIH grant AI074022.
NR 44
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Z9 9
U1 2
U2 6
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JAN
PY 2012
VL 9
IS 1
SI SI
BP 62
EP 74
DI 10.1038/cmi.2011.29
PG 13
WC Immunology
SC Immunology
GA 877RX
UT WOS:000299201200012
PM 21909127
ER
PT J
AU O'Connor, CM
Whellan, DJ
Wojdyla, D
Leifer, E
Clare, RM
Ellis, SJ
Fine, LJ
Fleg, JL
Zannad, F
Keteyian, SJ
Kitzman, DW
Kraus, WE
Rendall, D
Pina, IL
Cooper, LS
Fiuzat, M
Lee, KL
AF O'Connor, Christopher M.
Whellan, David J.
Wojdyla, Daniel
Leifer, Eric
Clare, Robert M.
Ellis, Stephen J.
Fine, Lawrence J.
Fleg, Jerome L.
Zannad, Faiez
Keteyian, Steven J.
Kitzman, Dalane W.
Kraus, William E.
Rendall, David
Pina, Ileana L.
Cooper, Lawton S.
Fiuzat, Mona
Lee, Kerry L.
TI Factors Related to Morbidity and Mortality in Patients With Chronic
Heart Failure With Systolic Dysfunction The HF-ACTION Predictive Risk
Score Model
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; systolic heart failure; risk assessment; Cox proportional
hazards models; exercise
ID CITY CARDIOMYOPATHY QUESTIONNAIRE; INITIATE LIFESAVING TREATMENT;
LEFT-VENTRICULAR DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; WORSENING
RENAL-FUNCTION; CORONARY-ARTERY DISEASE; PEAK OXYGEN-CONSUMPTION;
CLINICAL CHARACTERISTICS; MYOCARDIAL-INFARCTION; HOSPITALIZED-PATIENTS
AB Background-We aimed to develop a multivariable statistical model for risk stratification in patients with chronic heart failure with systolic dysfunction, using patient data that are routinely collected and easily obtained at the time of initial presentation.
Methods and Results-In a cohort of 2331 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing) study (New York Heart Association class II-IV, left ventricular ejection fraction <= 0.35, randomized to exercise training and usual care versus usual care alone, median follow-up of 2.5 years), we performed risk modeling using Cox proportional hazards models and analyzed the relationship between baseline clinical factors and the primary composite end point of death or all-cause hospitalization and the secondary end point of all-cause death alone. Prognostic relationships for continuous variables were examined using restricted cubic spline functions, and key predictors were identified using a backward variable selection process and bootstrapping methods. For ease of use in clinical practice, point-based risk scores were developed from the risk models. Exercise duration on the baseline cardiopulmonary exercise test was the most important predictor of both the primary end point and all-cause death. Additional important predictors for the primary end point risk model (in descending strength) were Kansas City Cardiomyopathy Questionnaire symptom stability score, higher serum urea nitrogen, and male sex (all P<0.0001). Important additional predictors for the mortality risk model were higher serum urea nitrogen, male sex, and lower body mass index (all P<0.0001).
Conclusions-Risk models using simple, readily obtainable clinical characteristics can provide important prognostic information in ambulatory patients with chronic heart failure with systolic dysfunction.
C1 [O'Connor, Christopher M.; Wojdyla, Daniel; Clare, Robert M.; Ellis, Stephen J.; Rendall, David; Fiuzat, Mona; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA.
[Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Leifer, Eric; Fine, Lawrence J.; Fleg, Jerome L.; Cooper, Lawton S.] NHLBI, Bethesda, MD 20892 USA.
[Zannad, Faiez] Nancy Univ, Nancy, France.
[Keteyian, Steven J.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Kitzman, Dalane W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA.
[Kraus, William E.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA.
[Kraus, William E.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Pina, Ileana L.] Montefiore Med Ctr, New York, NY USA.
RP O'Connor, CM (reprint author), DUMC Box 3356, Durham, NC 27710 USA.
EM Oconn002@mc.duke.edu
OI Kraus, William E/0000-0003-1930-9684
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health, Bethesda, MD
FX The HF-ACTION trial was funded by the National Heart, Lung, and Blood
Institute of the National Institutes of Health, Bethesda, MD.
NR 36
TC 67
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JAN
PY 2012
VL 5
IS 1
BP 63
EP 71
DI 10.1161/CIRCHEARTFAILURE.111.963462
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 879IY
UT WOS:000299324100015
PM 22114101
ER
PT J
AU Zhang, MC
Tavora, F
Oliveira, JB
Li, L
Franco, M
Fowler, D
Zhao, ZQ
Burke, A
AF Zhang, Mingchang
Tavora, Fabio
Oliveira, Joao Bosco
Li, Ling
Franco, Marcello
Fowler, David
Zhao, Ziqin
Burke, Allen
TI PKP2 Mutations in Sudden Death From Arrhythmogenic Right Ventricular
Cardiomyopathy (ARVC) and Sudden Unexpected Death With Negative Autopsy
(SUDNA)
SO CIRCULATION JOURNAL
LA English
DT Article
DE Arrhythmia; Arrhythmogenic right ventricular cardiomyopathy; Desmosome;
Negative autopsy; Sudden death
ID CARDIAC DEATH; PLAKOPHILIN-2 MUTATIONS; MOLECULAR AUTOPSY;
EPITHELIAL-CELLS; DYSPLASIA/CARDIOMYOPATHY; EXPRESSION; DESMOSOMES;
PROTEIN; GENE; DESMOCOLLIN-2
AB Background: Plakophilin2 (PKP2) is a desmosome-related protein with numerous armadillo repeats and has been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC). Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy, and have been linked to ion channel mutations in a subset of cases, but so far not to PKP2.
Methods and Results: We sequenced all 14 exons of PKP2 in DNA extracted from postmortem heart tissues of 25 patients dying from ARVC and 25 from sudden unexpected death with negative autopsy (SUDNA). The primers were designed using the Primer Express 3.0 software. Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130XL Genetic Analyzer. Mutation damage prediction was made using Mutation Taster, Polyphen and SIFT software. In 6 of the 25 ARVC samples, 6 PKP2 mutations were identified, 4 of which were likely significant, and 3 of which were novel (p.N641del, p.L64PfsX22, p.G269R). In 6 of the 25 cases of SUDNA samples, 6 PKP2 mutations were identified, 3 of which were likely significant, and 4 of which were not previously described (p.P665S, p.Y217TfsX45, p.E540, p.S615T).
Conclusions: PKP2 mutations are not specific for ARVC and may result in SUDNA. The link between ARVC and desmosomal mutations may not be causal but related to an association between defective desmosomal proteins and arrhythmias. (Circ J 2012; 76: 189-194)
C1 [Zhang, Mingchang; Li, Ling; Fowler, David; Zhao, Ziqin; Burke, Allen] Fudan Univ, Shanghai Med Coll, Dept Forens Med, Shanghai 200433, Peoples R China.
[Zhang, Mingchang; Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Tavora, Fabio] Messejana Heart & Lung Hosp, Fortaleza, Ceara, Brazil.
[Li, Ling; Fowler, David] China Univ Polit Sci & Law, Div Forens Med, Key Lab Evidence Sci, Beijing, Peoples R China.
[Zhang, Mingchang; Li, Ling; Fowler, David; Burke, Allen] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Tavora, Fabio; Franco, Marcello] Escola Paulista Med, BR-04023 Sao Paulo, Brazil.
RP Burke, A (reprint author), UMMS, 21 S Greene St, Baltimore, MD 21201 USA.
EM aburke@umm.edu
OI Oliveira, Joao/0000-0001-9388-8173
NR 38
TC 19
Z9 19
U1 2
U2 5
PU JAPANESE CIRCULATION SOC
PI KYOTO
PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO,
606-8305, JAPAN
SN 1346-9843
J9 CIRC J
JI Circ. J.
PD JAN
PY 2012
VL 76
IS 1
BP 189
EP 194
DI 10.1253/circj.CJ-11-0747
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 871XN
UT WOS:000298771100032
PM 22019812
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI On Drug Development, Chance, and the Prepared Mind
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Bldg 10,Room 12N226,900 Rockville Pike, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2012
VL 18
IS 1
BP 22
EP 22
DI 10.1158/1078-0432.CCR-11-2908
PG 1
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900005
PM 22215902
ER
PT J
AU Bates, SE
Amiri-Kordestani, L
Giaccone, G
AF Bates, Susan E.
Amiri-Kordestani, Laleh
Giaccone, Giuseppe
TI Drug Development: Portals of Discovery
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID REFRACTORY PROSTATE-CANCER; GROWTH-FACTOR RECEPTOR; RENAL-CELL
CARCINOMA; METASTATIC COLORECTAL-CANCER; RECURRENT OVARIAN-CANCER; ACUTE
MYELOID-LEUKEMIA; PHASE-III TRIAL; BREAST-CANCER; SOLID TUMORS;
LUNG-CANCER
AB A British humorist said, "There is much to be said for failure. It is much more interesting than success." This CCR Focus section is aimed at identifying lessons to be learned from difficulties encountered in recent years during development of anticancer agents. Clearly, we have not found a silver bullet tyrosine kinase inhibitor against solid tumors comparable with imatinib in chronic myelogenous leukemia. Although vemurafenib for B-Raf-mutated melanoma and crizotinib for non-small cell lung cancers with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements were developed rapidly and offer hope for individualized targeted therapies, the development of agents targeting a number of other pathways has been slower and less successful. These agents include drugs for blocking the insulin-like growth factor I/insulin receptor pathways, mitotic kinase inhibitors, and Hsp90 antagonists. Several potentially useful, if not groundbreaking, agents have had setbacks in clinical development, including trastuzumab emtansine, gemtuzumab ozogamicin, and satraplatin. From experience, we have learned the following: (i) not every altered protein or pathway is a valid anticancer target; (ii) drugs must effectively engage the target; (iii) the biology of the systems we use must be very well understood; and (iv) clinical trials must be designed to assess whether the drug reached and impaired the target. It is also important that we improve the drug development enterprise to enhance enrollment, streamline clinical trials, reduce financial risk, and encourage the development of agents for niche indications. Such enormous challenges are offset by potentially tremendous gains in our understanding and treatment of cancer. Clin Cancer Res; 18(1); 23-32. (C) 2012 AACR.
C1 [Bates, Susan E.; Amiri-Kordestani, Laleh; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 12N226,900 Rockville Pike, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 71
TC 23
Z9 23
U1 0
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 JAN 1
PY 2012
VL 18
IS 1
BP 23
EP 32
DI 10.1158/1078-0432.CCR-11-1001
PG 10
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900006
PM 22215903
ER
PT J
AU Komlodi-Pasztor, E
Sackett, DL
Fojo, AT
AF Komlodi-Pasztor, Edina
Sackett, Dan L.
Fojo, Antonio Tito
TI Inhibitors Targeting Mitosis: Tales of How Great Drugs against a
Promising Target Were Brought Down by a Flawed Rationale
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID AURORA-B KINASE; TUMOR DOUBLING TIME; POLO-LIKE KINASE; ADVANCED SOLID
TUMORS; BREAST-CANCER GROWTH; RENAL-CELL CARCINOMA; LUNG-CANCER;
NATURAL-HISTORY; SELECTIVE INHIBITOR; IN-VIVO
AB Although they have been advocated with an understandable enthusiasm, mitosis-specific agents such as inhibitors of mitotic kinases and kinesin spindle protein have not been successful clinically. These drugs were developed as agents that would build on the success of microtubule-targeting agents while avoiding the neurotoxicity that encumbers drugs such as taxanes and vinca alkaloids. The rationale for using mitosis-specific agents was based on the thesis that the clinical efficacy of microtubule-targeting agents could be ascribed to the induction of mitotic arrest. However, the latter concept, which has long been accepted as dogma, is likely important only in cell culture and rapidly growing preclinical models, and irrelevant in patient tumors, where interference with intracellular trafficking on microtubules is likely the principal mechanism of action. Here we review the preclinical and clinical data for a diverse group of inhibitors that target mitosis and identify the reasons why these highly specific, myelosuppressive compounds have failed to deliver on their promise. Clin Cancer Res; 18(1); 51-63. (C) 2012 AACR.
C1 [Komlodi-Pasztor, Edina; Fojo, Antonio Tito] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Fojo, AT (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1906,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA.
EM tfojo@helix.nih.gov
NR 121
TC 81
Z9 82
U1 2
U2 10
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 JAN 1
PY 2012
VL 18
IS 1
BP 51
EP 63
DI 10.1158/1078-0432.CCR-11-0999
PG 13
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900009
PM 22215906
ER
PT J
AU Neckers, L
Workman, P
AF Neckers, Len
Workman, Paul
TI Hsp90 Molecular Chaperone Inhibitors: Are We There Yet?
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HEAT-SHOCK-PROTEIN; BREAST-CANCER CELLS; PHASE-II TRIAL;
MULTIPLE-MYELOMA; TANESPIMYCIN 17-AAG; ACQUIRED-RESISTANCE; SIGNALING
PATHWAYS; CRYSTAL-STRUCTURE; TARGETING HSP90; DOSE-ESCALATION
AB Heat shock protein (Hsp) 90 is an ATP-dependent molecular chaperone that is exploited by malignant cells to support activated oncoproteins, including many cancer-associated kinases and transcription factors, and it is essential for oncogenic transformation. Originally viewed with skepticism, Hsp90 inhibitors are now being actively pursued by the pharmaceutical industry, with 17 agents having entered clinical trials. Investigators established Hsp90's druggability using the natural products geldanamycin and radicicol, which mimic the unusual ATP structure adopted in the chaperone's N-terminal nucleotide-binding pocket and cause potent and selective blockade of ATP binding/hydrolysis, inhibit chaperone function, deplete oncogenic clients, and show antitumor activity. Preclinical data obtained with these natural products have heightened interest in Hsp90 as a drug target, and 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) has shown clinical activity (as defined by Response Evaluation Criteria in Solid Tumors) in HER2+ breast cancer. Many optimized synthetic, small-molecule Hsp90 inhibitors from diverse chemotypes are now in clinical trials. Here, we review the discovery and development of Hsp90 inhibitors and assess their potential. There has been significant learning from studies of the basic biology of Hsp90, as well as translational drug development involving this chaperone, enhanced by the use of Hsp90 inhibitors as chemical probes. Success will likely lie in treating cancers that are addicted to particular driver oncogene products (e.g., HER2, ALK, EGFR, and BRAF) that are sensitive Hsp90 clients, as well as malignancies (especially multiple myeloma) in which buffering of proteotoxic stress is critical for survival. We discuss approaches for enhancing the effectiveness of Hsp90 inhibitors and highlight new chaperone and stress-response pathway targets, including HSF1 and Hsp70. Clin Cancer Res; 18(1); 64-76. (C) 2012 AACR.
C1 [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Workman, Paul] Inst Canc Res, Haddow Labs, Div Canc Therapeut,Canc Res UK Canc Therapeut Uni, Signal Transduct & Mol Pharmacol Team, Sutton SM2 5NG, Surrey, England.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10-CRC,Room 1-5940, Bethesda, MD 20892 USA.
EM neckersl@mail.nih.gov; paul.workman@icr.ac.uk
FU National Cancer Institute; Cancer Research UK [C309/A8274]; National
Health Service (NIHR Biomedical Research Centre)
FX Intramural Research Program of the National Cancer Institute (L.
Neckers); Cancer Research UK (program grant C309/A8274 to P. Workman);
National Health Service (NIHR Biomedical Research Centre; P. Workman).
P. Workman is a Cancer Research UK Life Fellow.
NR 115
TC 355
Z9 366
U1 14
U2 76
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2012
VL 18
IS 1
BP 64
EP 76
DI 10.1158/1078-0432.CCR-11-1000
PG 13
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900010
PM 22215907
ER
PT J
AU Kemp, CD
Rao, M
Xi, SC
Inchauste, S
Mani, H
Fetsch, P
Filie, A
Zhang, M
Hong, JA
Walker, RL
Zhu, YLJ
Ripley, RT
Mathur, A
Liu, F
Yang, MC
Meltzer, PA
Marquez, VE
De Rienzo, A
Bueno, R
Schrump, DS
AF Kemp, Clinton D.
Rao, Mahadev
Xi, Sichuan
Inchauste, Suzanne
Mani, Haresh
Fetsch, Patricia
Filie, Armando
Zhang, Mary
Hong, Julie A.
Walker, Robert L.
Zhu, Yuelin J.
Ripley, R. Taylor
Mathur, Aarti
Liu, Fang
Yang, Maocheng
Meltzer, Paul A.
Marquez, Victor E.
De Rienzo, Assunta
Bueno, Raphael
Schrump, David S.
TI Polycomb Repressor Complex-2 Is a Novel Target for Mesothelioma Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MALIGNANT PLEURAL MESOTHELIOMA; GROUP PROTEIN EED; STEM-CELLS; HISTONE
METHYLATION; X-CHROMOSOME; CANCER-CELLS; EZH2; EXPRESSION; GENE;
CARCINOMA
AB Purpose: Polycomb group (PcG) proteins are critical epigenetic mediators of stem cell pluripotency, which have been implicated in the pathogenesis of human cancers. This study was undertaken to examine the frequency and clinical relevance of PcG protein expression in malignant pleural mesotheliomas (MPM).
Experimental Design: Microarray, quantitative reverse transcriptase PCR (qRT-PCR), immunoblot, and immunohistochemistry techniques were used to examine PcG protein expression in cultured MPM, mesothelioma specimens, and normal mesothelial cells. Lentiviral short hairpin RNA techniques were used to inhibit EZH2 and EED expression in MPM cells. Proliferation, migration, clonogenicity, and tumorigenicity of MPM cells either exhibiting knockdown of EZH2 or EED, or exposed to 3-deazaneplanocin A (DZNep), and respective controls were assessed by cell count, scratch and soft agar assays, and murine xenograft experiments. Microarray and qRT-PCR techniques were used to examine gene expression profiles mediated by knockdown of EZH2 or EED, or DZNep.
Results: EZH2 and EED, which encode components of polycomb repressor complex-2 (PRC-2), were overexpressed in MPM lines relative to normal mesothelial cells. EZH2 was overexpressed in approximately 85% of MPMs compared with normal pleura, correlating with diminished patient survival. Overexpression of EZH2 coincided with decreased levels of miR-101 and miR-26a. Knockdown of EZH2 or EED, or DZNep treatment, decreased global H3K27Me3 levels, and significantly inhibited proliferation, migration, clonogenicity, and tumorigenicity of MPM cells. Common as well as differential gene expression profiles were observed following knockdown of PRC-2 members or DZNep treatment.
Conclusions: Pharmacologic inhibition of PRC-2 expression/activity is a novel strategy for mesothelioma therapy. Clin Cancer Res; 18(1); 77-90. (C) 2011 AACR.
C1 [Kemp, Clinton D.; Rao, Mahadev; Xi, Sichuan; Inchauste, Suzanne; Zhang, Mary; Hong, Julie A.; Ripley, R. Taylor; Mathur, Aarti; Liu, Fang; Yang, Maocheng; Schrump, David S.] NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Mani, Haresh; Fetsch, Patricia; Filie, Armando] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Walker, Robert L.; Zhu, Yuelin J.; Meltzer, Paul A.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Marquez, Victor E.] NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA.
[De Rienzo, Assunta; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA.
RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Room 4-3942,MSC 1201, Bethesda, MD 20892 USA.
EM David_Schrump@nih.gov
NR 49
TC 38
Z9 41
U1 1
U2 8
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 JAN 1
PY 2012
VL 18
IS 1
BP 77
EP 90
DI 10.1158/1078-0432.CCR-11-0962
PG 14
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900011
PM 22028491
ER
PT J
AU Welsh, AW
Lannin, DR
Young, GS
Sherman, ME
Figueroa, JD
Henry, NL
Ryden, L
Kim, C
Love, RR
Schiff, R
Rimm, DL
AF Welsh, Allison W.
Lannin, Donald R.
Young, Gregory S.
Sherman, Mark E.
Figueroa, Jonine D.
Henry, N. Lynn
Ryden, Lisa
Kim, Chungyeul
Love, Richard R.
Schiff, Rachel
Rimm, David L.
TI Cytoplasmic Estrogen Receptor in Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; AUTOMATED QUANTITATIVE-ANALYSIS; RETRACTED
ARTICLE. SEE; PLASMA-MEMBRANE; MONOCLONAL-ANTIBODIES; ENDOCRINE
RESISTANCE; TAMOXIFEN RESISTANCE; ADJUVANT TAMOXIFEN; ALPHA; CELLS
AB Purpose: In addition to genomic signaling, it is accepted that estrogen receptor-alpha (ER alpha) has nonnuclear signaling functions, which correlate with tamoxifen resistance in preclinical models. However, evidence for cytoplasmic ER localization in human breast tumors is less established. We sought to determine the presence and implications of nonnuclear ER in clinical specimens.
Experimental Design: A panel of ER alpha-specific antibodies (SP1, MC20, F10, 60c, and 1D5) was validated by Western blot and quantitative immunofluorescent (QIF) analysis of cell lines and patient controls. Then eight retrospective cohorts collected on tissue microarrays were assessed for cytoplasmic ER. Four cohorts were from Yale (YTMA 49, 107, 130, and 128) and four others (NCI YTMA 99, South Swedish Breast Cancer Group SBII, NSABP B14, and a Vietnamese Cohort) from other sites around the world.
Results: Four of the antibodies specifically recognized ER by Western and QIF analysis, showed linear increases in amounts of ER in cell line series with progressively increasing ER, and the antibodies were reproducible on YTMA 49 with Pearson correlations (r(2) values) ranging from 0.87 to 0.94. One antibody with striking cytoplasmic staining (MC20) failed validation. We found evidence for specific cytoplasmic staining with the other four antibodies across eight cohorts. The average incidence was 1.5%, ranging from 0 to 3.2%.
Conclusions: Our data show ER alpha is present in the cytoplasm in a number of cases using multiple antibodies while reinforcing the importance of antibody validation. In nearly 3,200 cases, cytoplasmic ER is present at very low incidence, suggesting its measurement is unlikely to be of routine clinical value. Clin Cancer Res; 18(1); 118-26. (C) 2011 AACR.
C1 [Welsh, Allison W.; Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Lannin, Donald R.] Yale Univ, Sch Med, Dept Surg & Oncol, New Haven, CT 06520 USA.
[Young, Gregory S.] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Sherman, Mark E.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Henry, N. Lynn] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Ryden, Lisa] Lund Univ, Dept Surg, Lund, Sweden.
[Kim, Chungyeul] Natl Surg Adjuvant Breast & Bowel Project Fdn, Div Pathol, Pittsburgh, PA USA.
[Love, Richard R.] Int Breast Canc Fdn, Madison, WI USA.
[Schiff, Rachel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Schiff, Rachel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
RP Rimm, DL (reprint author), Yale Univ, Sch Med, Dept Pathol, BML 116,310 Cedar St, New Haven, CT 06520 USA.
EM david.rimm@yale.edu
OI kim, chungyeul/0000-0002-9636-5228
FU National Cancer Institute; NIH [R33 CA 106709]; US Army CDMRP; American
Society of Clinical Oncology
FX The study was supported by additional grants from the Intramural
Research Program of the National Cancer Institute to M.E. Sherman and
J.D. Figueroa, and an American Society of Clinical Oncology Young
Investigator award to N.L. Henry. The support for this research comes
from NIH R33 CA 106709 (to D.L. Rimm) and a US Army CDMRP pre-doctoral
fellowship (A.W. Welsh).
NR 49
TC 25
Z9 25
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2012
VL 18
IS 1
BP 118
EP 126
DI 10.1158/1078-0432.CCR-11-1236
PG 9
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900014
PM 21980134
ER
PT J
AU Singh, R
Zhang, YJ
Pastan, I
Kreitman, RJ
AF Singh, Rajat
Zhang, Yujian
Pastan, Ira
Kreitman, Robert J.
TI Synergistic Antitumor Activity of Anti-CD25 Recombinant Immunotoxin
LMB-2 with Chemotherapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HAIRY-CELL LEUKEMIA; ANTI-MESOTHELIN IMMUNOTOXIN; NUDE-MICE BEARING;
PHASE-I TRIAL; RFB4(DSFV)-PE38 BL22; PSEUDOMONAS EXOTOXIN; HUMAN
CARCINOMA; ANTI-B4-BLOCKED RICIN; MULTIDRUG-RESISTANT; CYTOTOXIC
ACTIVITY
AB Purpose: Although anti-CD25 recombinant immunotoxin LMB-2 is effective against CD25(+) hairy cell leukemia, activity against more aggressive diseases such as adult T-cell leukemia (ATL) is limited by rapid disease progression between treatment cycles. Our goal was to determine in vivo whether rapid growth of CD25(+) tumor is associated with high levels of tumor interstitial soluble CD25 (sCD25) and whether chemotherapy can reduce tumor sCD25 and synergize with LMB-2.
Experimental Design: Tumor xenografts expressing human CD25 were grown in mice, which were then treated with LMB-2 and chemotherapy either alone or in combination, and sCD25 level and antitumor activity were measured.
Results: CD25(+) human xenografts growing rapidly in nude mice had intratumoral sCD25 at levels that were between 21- and 2,200 (median 118)-fold higher than in serum, indicating that interstitial sCD25 interacts with LMB-2 in tumors. Intratumoral sCD25 levels were in the range 21 to 157 (median 54) ng/mL without treatment and 0.95 to 6.1 (median 2.6) ng/mL (P < 0.0001) 1 day after gemcitabine administration. CD25(+) xenografts that were too large to regress with LMB-2 alone were minimally responsive to gemcitabine alone but completely regressed with the combination. Ex vivo, different ratios of gemcitabine and LMB-2 were cytotoxic to the CD25(+) tumor cells in an additive, but not synergistic, manner.
Conclusions: Gemcitabine is synergistic with LMB-2 in vivo unrelated to improved cytotoxicity. Synergism, therefore, appears to be related to improved distribution of LMB-2 to CD25(+) tumors, and is preceded by decreased sCD25 within the tumor because of chemotherapy. To test the concept of combined treatment clinically, patients with relapsed/refractory ATL are being treated with fludarabine plus cyclophosphamide before LMB-2. Clin Cancer Res; 18(1); 152-60. (C) 2011 AACR.
C1 [Singh, Rajat; Zhang, Yujian; Pastan, Ira; Kreitman, Robert J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5124B,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kreitmar@mail.nih.gov
OI Singh, Rajat/0000-0002-9542-1929
FU National Cancer Institute, NIH
FX This work was supported by the intramural research program from National
Cancer Institute, NIH.
NR 49
TC 14
Z9 15
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 JAN 1
PY 2012
VL 18
IS 1
BP 152
EP 160
DI 10.1158/1078-0432.CCR-11-1839
PG 9
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900017
PM 22068660
ER
PT J
AU Qayum, N
Im, J
Stratford, MR
Bernhard, EJ
McKenna, WG
Muschel, RJ
AF Qayum, Naseer
Im, Jaehong
Stratford, Michael R.
Bernhard, Eric J.
McKenna, W. Gillies
Muschel, Ruth J.
TI Modulation of the Tumor Microvasculature by Phosphoinositide-3 Kinase
Inhibition Increases Doxorubicin Delivery In Vivo
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSELS; VASCULAR NORMALIZATION;
SIGNALING PATHWAY; NECK-CANCER; NUDE-MICE; ANGIOGENESIS; HYPOXIA;
MICROENVIRONMENT; ABNORMALITIES
AB Purpose: Because effective drug delivery is often limited by inadequate vasculature within the tumor, the ability to modulate the tumor microenvironment is one strategy that may achieve better drug distribution. We have previously shown that treatment of mice bearing tumors with phosphoinositide-3 kinase (PI3K) inhibitors alters vascular structure in a manner analogous to vascular normalization and results in increased perfusion of the tumor. On the basis of that result, we asked whether inhibition of PI3K would improve chemotherapy delivery.
Experimental Design: Mice with xenografts using the cell line SQ20B bearing a hypoxia marker or MMTV-neu transgenic mice with spontaneous breast tumors were treated with the class I PI3K inhibitor GDC-0941. The tumor vasculature was evaluated by Doppler ultrasound, and histology. The delivery of doxorubicin was assessed using whole animal fluorescence, distribution on histologic sections, high-performance liquid chromatography on tumor lysates, and tumor growth delay.
Results: Treatment with GDC-0941 led to approximately three-fold increases in perfusion, substantially reduced hypoxia and vascular normalization by histology. Significantly increased amounts of doxorubicin were delivered to the tumors correlating with synergistic tumor growth delay. The GDC-0941 itself had no effect on tumor growth.
Conclusion: Inhibition of PI3K led to vascular normalization and improved delivery of a chemotherapeutic agent. This study highlights the importance of the microvascular effects of some novel oncogenic signaling inhibitors and the need to take those changes into account in the design of clinical trials many of which use combinations of chemotherapeutic agents. Clin Cancer Res; 18(1); 161-9. (C) 2011 AACR.
C1 [Qayum, Naseer; Im, Jaehong; Stratford, Michael R.; McKenna, W. Gillies; Muschel, Ruth J.] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England.
[Bernhard, Eric J.] NCI, Radiotherapy Dev Branch, Radiat Res Program, Div Canc Treatment & Diag,NIH, Rockville, MD USA.
RP Muschel, RJ (reprint author), Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England.
EM ruth.muschel@rob.ox.ac.uk
FU Medical Research Council-Cancer Research UK; CRUK/EPSRC [NIH RO1
CA73820, NIH PO1 CA75138]; U.S. Department of Defense BCCOE; Cancer
Research UK; NIH [RO1 CA73820, PO1 CA75138]
FX The study was supported by Medical Research Council-Cancer Research UK
grant-in-aid. Oxford Cancer Imaging Centre was supported by CRUK/EPSRC
(N. Qayum, J. Im, M.R. Stratford, E. J. Bernhard, W.G. McKenna, and R.J.
Muschel), NIH RO1 CA73820 (E.J. Bernhard), and NIH PO1 CA75138 (W.G.
McKenna, E.J. Bernhard) and U.S. Department of Defense BCCOE grant (R.J.
Muschel). N. Qayum was supported by a Cancer Research UK studentship.
NR 39
TC 23
Z9 23
U1 0
U2 8
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 JAN 1
PY 2012
VL 18
IS 1
BP 161
EP 169
DI 10.1158/1078-0432.CCR-11-1413
PG 9
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900018
PM 22065081
ER
PT J
AU Wright, LN
Ryscavage, A
Merlino, G
Yuspa, SH
AF Wright, Lisa Nolan
Ryscavage, Andrew
Merlino, Glenn
Yuspa, Stuart H.
TI Modeling the Transcriptional Consequences of Epidermal Growth Factor
Receptor Ablation in Ras-Initiated Squamous Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE
INHIBITORS; GENE-EXPRESSION PATTERNS; CARCINOMA-CELLS; BREAST-CANCER;
IN-VIVO; ERLOTINIB; EGFR; KRAS
AB Purpose: Epidermal growth factor receptor (EGFR)-targeted therapy is in clinical use to treat squamous cell carcinoma of the head and neck and other cancers of lining epithelium. RAS mutations in these tumors are a negative prognostic factor for response, and skin inflammation is an adverse reaction to therapy. We investigated transcriptional and biochemical changes that could account for the confounding effects of RAS activation and inflammation in a squamous tissue.
Experimental Design: We carried out gene expression profiling on oncogenic Ras-transformed and wildtype mouse and human keratinocytes with EGFR ablated chronically by genetic deletion or acutely by drug treatment and followed leads provided by pathway analysis with biochemical studies.
Results: We identified a 25-gene signature specific to the Ras-EGFR ablation interaction and a distinct 19-gene EGFR ablation signature on normal keratinocytes. EGFR ablation in the context of wild-type Ras reduces ontologies favoring cell-cycle control and transcription, whereas oncogenic Ras enriches ontologies for ion channels and membrane transporters, particularly focused on calcium homeostasis. Ontologies between chronic EGFR ablation and acute pharmacologic ablation were unique, both with and without Ras activation. p38 alpha is activated in response to abrogation of EGFR signaling under conditions of Ras activation in both mouse and human keratinocytes and in RAS-transformed tumor orthografts of EGFR-ablated mouse keratinocytes. EGFR ablation in the absence of oncogenic Ras revealed Erk and interleukin-1 beta-related pathways.
Conclusion: These findings reveal unrecognized interactions between Ras and EGFR signaling in squamous tumor cells that could influence the therapeutic response to EGFR ablation therapy. Clin Cancer Res; 18(1); 170-83. (C) 2011 AACR.
C1 [Wright, Lisa Nolan; Ryscavage, Andrew; Merlino, Glenn; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4068, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute
FX This work was supported by the intramural program of the Center for
Cancer Research, National Cancer Institute.
NR 49
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U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2012
VL 18
IS 1
BP 170
EP 183
DI 10.1158/1078-0432.CCR-11-1349
PG 14
WC Oncology
SC Oncology
GA 871SV
UT WOS:000298758900019
PM 22068661
ER
PT J
AU Schnabel, RB
Baccarelli, A
Lin, HH
Ellinor, PT
Benjamin, EJ
AF Schnabel, Renate B.
Baccarelli, Andrea
Lin, Honghuang
Ellinor, Patrick T.
Benjamin, Emelia J.
TI Next Steps in Cardiovascular Disease Genomic Research-Sequencing,
Epigenetics, and Transcriptomics
SO CLINICAL CHEMISTRY
LA English
DT Review
ID CORONARY-ARTERY-DISEASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; COPY NUMBER
VARIANTS; DNA METHYLATION; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; WIDE
ASSOCIATION; HEART-FAILURE; CHROMATIN MODIFICATIONS; CARDIAC-HYPERTROPHY
AB BACKGROUND: Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last 5 years. In most cases, however, these groundbreaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions.
CONTENT: We reviewed the scientific literature published in English for novel methods and promising genomic targets that would permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in 3 key areas will be critical for the success of these projects. First, exome-centered and whole-genome next-generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research is increasingly acknowledging that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore, we expect that multiple epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Lever-aging existing large-scale consortia and clinical biobanks in combination with electronic health records holds promise for integrating epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data.
SUMMARY: Novel methods in sequencing, epigenetics, and transcriptomics, plus unprecedented large-scale cooperative efforts, promise to generate insights into the complexity of CVD. The rapid accumulation and integration of knowledge will shed light on a considerable proportion of the missing heritability for CVD. (C) 2011 American Association for Clinical Chemistry
C1 [Schnabel, Renate B.] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.
[Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Lab Environm Epigenet, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA.
[Lin, Honghuang; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Lin, Honghuang; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
RP Schnabel, RB (reprint author), Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.
EM schnabelr@gmx.de
RI Schnabel, Renate/F-6527-2014;
OI Lin, Honghuang/0000-0003-3043-3942; Baccarelli,
Andrea/0000-0002-3436-0640; Benjamin, Emelia/0000-0003-4076-2336
FU Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial
Fibrillation at Boston University"; Deutsche Forschungsgemeinschaft
(German Research Foundation) [SCHN 1149/3-1]; National Institute of
Environmental Health Sciences [P30ES000002, R21ES019773, R01ES015172];
NIH [1R01HL092577, 5R21DA027021, 5R01HL104156, 1K24HL105780,
1RC1HL101056, 1R01HL102214, 1R01AG028321]
FX Evans Center for Interdisciplinary Biomedical Research ARC on "Atrial
Fibrillation at Boston University"
(http://www.bumc.bu.edu/evanscenteribr/). R. Schnabel, Deutsche
Forschungsgemeinschaft (German Research Foundation) Emmy Noether Program
SCHN 1149/3-1; A. Baccarelli, National Institute of Environmental Health
Sciences grants P30ES000002, R21ES019773, and R01ES015172; P. Ellinor,
NIH grants 1R01HL092577, 5R21DA027021, 5R01HL104156, and 1K24HL105780;
E. Benjamin, NIH grants 1R01HL092577, 1RC1HL101056, 1R01HL102214, and
1R01AG028321.
NR 100
TC 28
Z9 29
U1 1
U2 18
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 JAN
PY 2012
VL 58
IS 1
BP 113
EP 126
DI 10.1373/clinchem.2011.170423
PG 14
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 875RQ
UT WOS:000299052700020
PM 22100807
ER
PT J
AU Kwong, PD
Mascola, JR
Nabel, GJ
AF Kwong, Peter D.
Mascola, John R.
Nabel, Gary J.
TI Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to
HIV-1
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; RECOMBINANT
GLYCOPROTEIN-120 VACCINE; GP120 ENVELOPE GLYCOPROTEIN; CROSS-CLADE
NEUTRALIZATION; CORECEPTOR BINDING-SITE; STRUCTURAL BASIS; POTENT
NEUTRALIZATION; INFECTED INDIVIDUALS; CRYSTAL-STRUCTURE
AB The development of a highly effective AIDS vaccine will likely depend on success in designing immunogens that elicit broadly neutralizing antibodies to naturally circulating strains of HIV-1. Although the antibodies induced after natural infection with HIV-1 are often directed to strain-specific or nonneutralizing determinants, it is now evident that 10%-25% of HIV-infected individuals generate neutralizing antibody responses of considerable breadth. In the past, only four broadly neutralizing monoclonal antibodies had been defined, but more than a dozen monoclonal antibodies of substantial breadth have more recently been isolated. An understanding of their recognition sites, the structural basis of their interaction with the HIV Env, and their development pathways provides new opportunities to design vaccine candidates that will elicit broadly protective antibodies against this virus.
C1 [Kwong, Peter D.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
NR 102
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U1 0
U2 7
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD JAN
PY 2012
VL 4
IS 1
AR a007278
DI 10.1101/cshperspect.a007278
PG 16
WC Cell Biology
SC Cell Biology
GA 877GO
UT WOS:000299165700005
ER
PT J
AU Shui, GH
Bendt, AK
Jappar, IA
Lim, HM
Laneelle, M
Herve, M
Via, LE
Chua, GH
Bratschi, MW
Rahim, SZZ
Michelle, ALT
Hwang, SH
Lee, JS
Eum, SY
Kwak, HK
Daffe, M
Dartois, V
Michel, G
Barry, CE
Wenk, MR
AF Shui, Guanghou
Bendt, Anne K.
Jappar, Ignasius A.
Lim, Hui Ming
Laneelle, Marie
Herve, Maxime
Via, Laura E.
Chua, Gek Huey
Bratschi, Martin W.
Rahim, Siti Zarina Zainul
Michelle, Ang Lay Teng
Hwang, Soo-Hee
Lee, Jong-Soek
Eum, Seok-Yong
Kwak, Hyun-Kyung
Daffe, Mamadou
Dartois, Veronique
Michel, Gerd
Barry, Clifton E., III
Wenk, Markus R.
TI Mycolic acids as diagnostic markers for tuberculosis case detection in
humans and drug efficacy in mice
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE diagnostic marker; lipidomics; mass spectrometry; Mycobacterium
tuberculosis; mycolic acids
ID REAL-TIME PCR; MYCOBACTERIUM-TUBERCULOSIS; LIPIDS; IDENTIFICATION;
CHEMOTHERAPY; VIRULENCE; SAMPLES
AB Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection because they are bacteria-derived, contain information about bacterial species, modulate hostpathogen interactions and are chemically inert. Here, we present a novel approach based on mass spectrometry. Quantification of specific precursor fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity. We next used this tool in a retrospective casecontrol study of patients with pulmonary TB with varying disease burdens from South Korea, Vietnam, Uganda and South Africa. MAs were extracted from small volume sputum (200 mu l) and analysed without the requirement for derivatization. Infected patients (70, 19 of whom were HIV+) could be separated from controls (40, 20 of whom were HIV+) with a sensitivity and specificity of 94 and 93%, respectively. Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment. Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection.
C1 [Shui, Guanghou; Bendt, Anne K.; Jappar, Ignasius A.; Lim, Hui Ming; Chua, Gek Huey; Bratschi, Martin W.; Wenk, Markus R.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore.
[Laneelle, Marie; Daffe, Mamadou] IPBS UMR, Dept Mecanismes Mol Infect Mycobacteriennes, Toulouse, France.
[Herve, Maxime; Dartois, Veronique] Novartis Inst Trop Dis, Singapore, Singapore.
[Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bratschi, Martin W.; Wenk, Markus R.] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Rahim, Siti Zarina Zainul; Michelle, Ang Lay Teng] Natl Univ Singapore, Dept Microbiol, Singapore 117595, Singapore.
[Hwang, Soo-Hee] Natl Masan TB Hosp, Masan, South Korea.
[Lee, Jong-Soek; Eum, Seok-Yong; Kwak, Hyun-Kyung] Int TB Res Ctr, Masan, South Korea.
[Dartois, Veronique; Wenk, Markus R.] Natl Univ Singapore, Dept Biol Sci, Singapore 117595, Singapore.
[Michel, Gerd] Fdn Innovat New Diagnost FIND, Geneva, Switzerland.
RP Shui, GH (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore.
EM guanghou_shui@nuhs.edu.sg; markus_wenk@nuhs.edu.sg
RI Barry, III, Clifton/H-3839-2012; Bratschi, Martin/A-4386-2013; Wenk,
Markus/D-1441-2014;
OI Bratschi, Martin/0000-0003-0825-1587; Via, Laura/0000-0001-6074-9521
FU National Research Foundation [2007-04]; Academic Research Fund
[R-183-000-160-112]; Biomedical Research Council of Singapore
[R-183-000-211-305]; National Medical Research Council
[R-183-000-224-213]; NIH, NIAID; European Community
[HEALTH-F4-2010-241587]
FX We thank Sindhu Ravindranand and Hui Chien Tay (NITD) for help with
animal experiments and Xueli Guan (NUS) for technical assistance with
figures. We are grateful to Kenneth Olivier (NIH) for providing NTM
specimens. Special thanks are also due to Eloise Valli and Catharina
Boehme (FIND) for their excellent help in managing the clinical samples
from the FIND repository. This work was supported by the National
Research Foundation (under CRP Award No. 2007-04), the Academic Research
Fund (R-183-000-160-112), the Biomedical Research Council of Singapore
(R-183-000-211-305), the National Medical Research Council
(R-183-000-224-213) and partly by the Intramural Research Program of the
NIH, NIAID. Work in the laboratory of MD was supported in part by a
grant (SysteMTb HEALTH-F4-2010-241587) from the European Community.
NR 23
TC 18
Z9 18
U1 2
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD JAN
PY 2012
VL 4
IS 1
BP 27
EP 37
DI 10.1002/emmm.201100185
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 870MB
UT WOS:000298672300004
PM 22147526
ER
PT J
AU Grallert, H
Dupuis, J
Bis, JC
Dehghan, A
Barbalic, M
Baumert, J
Lu, C
Smith, NL
Uitterlinden, AG
Roberts, R
Khuseyinova, N
Schnabel, RB
Rice, KM
Rivadeneira, F
Hoogeveen, RC
Fontes, JD
Meisinger, C
Keaney, JF
Lemaitre, R
Aulchenko, YS
Vasan, RS
Ellis, S
Hazen, SL
van Duijn, CM
Nelson, JJ
Marz, W
Schunkert, H
McPherson, RM
Stirnadel-Farrant, HA
Psaty, BM
Gieger, C
Siscovick, D
Hofman, A
Illig, T
Cushman, M
Yamamoto, JF
Rotter, JI
Larson, MG
Stewart, AFR
Boerwinkle, E
Witteman, JCM
Tracy, RP
Koenig, W
Benjamin, EJ
Ballantyne, CM
AF Grallert, Harald
Dupuis, Josee
Bis, Joshua C.
Dehghan, Abbas
Barbalic, Maja
Baumert, Jens
Lu, Chen
Smith, Nicholas L.
Uitterlinden, Andre G.
Roberts, Robert
Khuseyinova, Natalie
Schnabel, Renate B.
Rice, Kenneth M.
Rivadeneira, Fernando
Hoogeveen, Ron C.
Fontes, Joao Daniel
Meisinger, Christa
Keaney, John F., Jr.
Lemaitre, Rozenn
Aulchenko, Yurii S.
Vasan, Ramachandran S.
Ellis, Stephen
Hazen, Stanley L.
van Duijn, Cornelia M.
Nelson, Jeanenne J.
Maerz, Winfried
Schunkert, Heribert
McPherson, Ruth M.
Stirnadel-Farrant, Heide A.
Psaty, Bruce M.
Gieger, Christian
Siscovick, David
Hofman, Albert
Illig, Thomas
Cushman, Mary
Yamamoto, Jennifer F.
Rotter, Jerome I.
Larson, Martin G.
Stewart, Alexandre F. R.
Boerwinkle, Eric
Witteman, Jacqueline C. M.
Tracy, Russell P.
Koenig, Wolfgang
Benjamin, Emelia J.
Ballantyne, Christie M.
TI Eight genetic loci associated with variation in lipoprotein-associated
phospholipase A2 mass and activity and coronary heart disease:
meta-analysis of genome-wide association studies from five
community-based studies
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Genome-wide association; Inflammation; Lipoprotein-associated
phospholipase A2
ID ACTIVATING-FACTOR-ACETYLHYDROLASE; ARTERY-DISEASE; ATHEROSCLEROTIC
PLAQUE; CARDIOVASCULAR-DISEASE; A(2); RISK; CHOLESTEROL; VARIANTS;
RECEPTOR; EPIDEMIOLOGY
AB Aims Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.
Methods and results In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 x 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 x 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study.
Conclusion Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.
C1 [Grallert, Harald; Baumert, Jens; Meisinger, Christa; Gieger, Christian; Illig, Thomas] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Dupuis, Josee; Schnabel, Renate B.; Fontes, Joao Daniel; Vasan, Ramachandran S.; Yamamoto, Jennifer F.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Dupuis, Josee; Lu, Chen] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Bis, Joshua C.; Lemaitre, Rozenn] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.; Lemaitre, Rozenn; Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA.
[Dehghan, Abbas; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; van Duijn, Cornelia M.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Smith, Nicholas L.; Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Dept Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Roberts, Robert; McPherson, Ruth M.; Stewart, Alexandre F. R.] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Khuseyinova, Natalie; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89081 Ulm, Germany.
[Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Div Atherosclerosis & Vasc Med, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA.
[Fontes, Joao Daniel; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Cardiol, Boston, MA 02118 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA.
[Ellis, Stephen; Hazen, Stanley L.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Nelson, Jeanenne J.] GlaxoSmithKline Inc, Worldwide Epidemiol, Res Triangle Pk, NC USA.
[Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, Heidelberg, Germany.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Maerz, Winfried] Univ Heidelberg, Med Fac Mannheim, Inst Publ Hlth Social & Prevent Med, Heidelberg, Germany.
[Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Stirnadel-Farrant, Heide A.] GlaxoSmithKline Inc, Worldwide Epidemiol, Harlow, Essex, England.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Illig, Thomas] Univ Munich, Inst Med Data Management Biometr & Epidemiol, Chair Epidemiol, Munich, Germany.
[Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
[Dupuis, Josee; Schnabel, Renate B.; Fontes, Joao Daniel; Vasan, Ramachandran S.; Yamamoto, Jennifer F.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
RP Koenig, W (reprint author), German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
EM wolfgang.koenig@uniklinik-ulm.de; cmb@bcm.tmc.edu
RI Stewart, Alexandre/A-5677-2011; Rice, Kenneth/A-4150-2013; Grallert,
Harald/B-3424-2013; Aulchenko, Yurii/M-8270-2013; Meisinger,
Christine/B-5358-2014; Schnabel, Renate/F-6527-2014; Lu,
Chen/D-8514-2015; Rivadeneira, Fernando/O-5385-2015;
OI Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336;
Gieger, Christian/0000-0001-6986-9554; Meisinger,
Christa/0000-0002-9026-6544; Dehghan, Abbas/0000-0001-6403-016X; Rice,
Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575;
Rivadeneira, Fernando/0000-0001-9435-9441; Larson,
Martin/0000-0002-9631-1254; Stewart, Alexandre/0000-0003-2673-9164;
Ramachandran, Vasan/0000-0001-7357-5970
FU Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE)
Consortium; National Heart, Lung, and Blood Institute [N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, U01 HL080295, R01 HL087652]; National Human Genome
Research Institute [U01HG004402]; National Institutes of Health
[HSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research;
National Institute of Neurological Disorders and Stroke; Cedars-Sinai
Board of Governors' Chair in Medical Genetics; National Center for
Research Resources [M01RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; GlaxoSmithKline; National
Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Affymetrix, Inc., for genotyping services
[N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center; Deutsche Forschungsgemeinschaft (German Research Foundation)
[SCHN 1149/1-1]; Erasmus Medical Center; Erasmus University Rotterdam;
Netherlands Organization for Scientific Research; Netherlands
Organization for Health Research and Development (ZonMw); Research
Institute for Diseases in the Elderly; Netherlands Heart Foundation;
Ministry of Education, Culture and Science; Ministry of Health Welfare
and Sports; European Commission; Municipality of Rotterdam; Netherlands
Organization for Scientific Research (NWO) [175.010.2005.011,
911.03.012, 918-76-619]; Research Institute for Diseases in the Elderly
(RIDE2) [014-93-015]; Netherlands Genomics Initiative (NGI)/NWO
[050-060-810]; Helmholtz Zentrum Munchen; German Research Center for
Environmental Health, Neuherberg, Germany; German Federal Ministry of
Education and Research (BMBF); German National Genome Research Network
(NGFNPlus) [01GS0834]; University of Ulm; Munich Center of Health
Sciences (MC Health); diaDexus; NGFN; CADnet BMBF; [HL64753];
[HL076784]; [AG028321]
FX The authors thank the staff and participants of the individual studies
for their important contributions, and acknowledge the essential role of
the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE)
Consortium in the development and support of this manuscript. CHARGE
members include NHLBI's ARIC Study, Cardiovascular Health Study, and
Framingham Heart Study; NIA's Iceland Age, Gene/Environment
Susceptibility (AGES) Study; and the Netherland's Rotterdam Study.; The
Atherosclerosis Risk in Communities (ARIC) Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HSN268200625226C. Infrastructure was partly supported by grant number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. The Cardiovascular Health Study research
reported in this article was supported by contract numbers N01-HC-85079
through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222,
N01-HC-75150, and N01-HC-45133 and grant numbers U01 HL080295 and R01
HL087652 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. A full list of principal CHS investigators and
institutions can be found at http://www.chs-nhlbi.org/pi.htm. DNA
handling and genotyping was supported in part by the Cedars-Sinai Board
of Governors' Chair in Medical Genetics (J.L.R.), the National Center
for Research Resources grant M01RR00425 to the Cedars-Sinai General
Clinical Research Center Genotyping core, and the National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. Lp-PLA2
measurements were funded by a grant from GlaxoSmithKline. The Framingham
Heart Study was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract number N01-HC-25195) and
its contract with Affymetrix, Inc., for genotyping services (contract
number N02-HL-6-4278). A portion of this research utilized the Linux
Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson
Evans Endowment of the Department of Medicine at Boston University
School of Medicine and Boston Medical Center. The analyses reflect
intellectual input and resource development from the Framingham Heart
Study investigators participating in the SNP Health Association Resource
(SHARe) project; grants HL64753, HL076784, and AG028321 (E.J.B.); and
Deutsche Forschungsgemeinschaft (German Research Foundation) Research
Fellowship SCHN 1149/1-1 (R.B.S.). Lp-PLA2 activity measurements were
provided by GlaxoSmithKline and mass measurements by diaDexus at no cost
to the FHS. The Rotterdam Study is supported by the Erasmus Medical
Center and Erasmus University Rotterdam; the Netherlands Organization
for Scientific Research; the Netherlands Organization for Health
Research and Development (ZonMw); the Research Institute for Diseases in
the Elderly; The Netherlands Heart Foundation; the Ministry of
Education, Culture and Science; the Ministry of Health Welfare and
Sports; the European Commission; and the Municipality of Rotterdam.
Support for genotyping was provided by the Netherlands Organization for
Scientific Research (NWO) (175.010.2005.011, 911.03.012) and Research
Institute for Diseases in the Elderly (RIDE2) (014-93-015). This study
was supported by the Netherlands Genomics Initiative (NGI)/NWO project
number 050-060-810. Abbas Dehghan is supported by a grant from NWO
(Vici, 918-76-619). The MONICA/KORA Augsburg studies were financed by
the Helmholtz Zentrum Munchen, German Research Center for Environmental
Health, Neuherberg, Germany, and supported by grants from the German
Federal Ministry of Education and Research (BMBF).; Part of this work
was financed bythe German National Genome Research Network (NGFNPlus,
project number 01GS0834) and through additional funds from the
University of Ulm. Furthermore, the research was supported within the
Munich Center of Health Sciences (MC Health) as part of LMU innovative.;
Lp-PLA2 activity measurements were provided by GlaxoSmithKline and mass
measurements by diaDexus at no cost to the FHS. R.R. has been consultant
to Cumberland Pharmaceuticals and Celera. R.C.H. has received
research/grant support from diaDexus for Lp-PLA2 work in ARIC. J.J.N. is
an employee of GlaxoSmithKline. H. S. has received research grants from
the EU, project Cardiogenics; NGFN, project Atherogenomics; and CADnet
BMBF. H.A.S.-F. is an employee of GlaxoSmithKline. B.M.P. serves on a
data and safety monitoring board for a device clinical trial funded by
Zoll Lifecor. M. C. has been consultant for GlaxoSmithKline in relation
to Lp-PLA2 and had grant funding from them for same. R.P.T.'s laboratory
has received support from GlaxoSmithKline in the form of free assay kits
for Lp-PLA2 measurements. W.K. has received honoraria for lectures from
diaDexus and GlaxoSmithKline, and is a member of the Steering Committee
of the GlaxoSmithKline-sponsored STABILITY and SOLID trials. C.M.B. has
received research/grant support from GlaxoSmithKline and diaDexus, and
consulting honoraria from GlaxoSmithKline. All other authors have no
conflict of interest to declare.
NR 37
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U1 0
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD JAN
PY 2012
VL 33
IS 2
BP 238
EP 251
DI 10.1093/eurheartj/ehr372
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 879RU
UT WOS:000299350500020
PM 22003152
ER
PT J
AU Semba, RD
Ang, A
Talegawkar, S
Crasto, C
Dalal, M
Jardack, P
Traber, MG
Ferrucci, L
Arab, L
AF Semba, R. D.
Ang, A.
Talegawkar, S.
Crasto, C.
Dalal, M.
Jardack, P.
Traber, M. G.
Ferrucci, L.
Arab, L.
TI Dietary intake associated with serum versus urinary
carboxymethyl-lysine, a major advanced glycation end product, in adults:
the Energetics Study
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE advanced glycation end products; carboxymethyl-lysine; diet; 24-h
dietary recall; food
ID CARDIOVASCULAR-DISEASE MORTALITY; LIQUID-CHROMATOGRAPHY; MAILLARD
REACTION; HUMAN HEALTH; ENDPRODUCTS; WOMEN; FOOD; GLYCOTOXINS; SYSTEMS;
OBESE
AB Background/Objectives: Advanced glycation end products (AGEs) are implicated in the pathogenesis of atherosclerosis, diabetes and kidney disease. The objective was to describe dietary intake, the dominant source of exposure to AGEs, with carboxymethyl-lysine (CML), a major AGE, in serum and urine, respectively.
Subjects/Methods: Serum and urinary CML were measured in 261 adults, aged 21-69 years, and compared with diet as assessed by six separate 24-h dietary recalls.
Results: Median (25th, 75th percentile) serum and urinary CML concentrations were 686 (598, 803) mu g/l and 1023 (812, 1238) mu g/gm creatinine. There was no correlation between serum and urinary CML (r = -0.02, P = 0.78). Serum CML was positively correlated with intake of soy, fruit juice, cold breakfast cereal, non-fat milk, whole grains, fruit, non-starchy vegetables and legumes, and negatively correlated with intake of red meat. Intake of fast food was not significantly correlated with serum CML. Urinary CML was positively correlated with intake of starchy vegetables, whole grains, sweets, nuts/seeds and chicken, and negatively correlated with intake of fast foods. Intake of AGE-rich foods such as fried chicken, French fries, bacon/sausage and crispy snacks were not significantly correlated with serum or urinary CML, except for a significant negative correlation between fried chicken and serum CML.
Conclusions: These findings suggest that the high consumption of foods considered high in CML is not a major determinant of either serum or urinary CML. Further work is needed to understand the relationship of AGEs in blood and urine with the metabolism of dietary AGEs. European Journal of Clinical Nutrition (2012) 66, 3-9; doi:10.1038/ejcn.2011.139; published online 27 July 2011
C1 [Semba, R. D.; Crasto, C.; Dalal, M.] Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Baltimore, MD 21287 USA.
[Ang, A.; Jardack, P.; Arab, L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Ang, A.; Jardack, P.; Arab, L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Talegawkar, S.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD USA.
[Traber, M. G.] Oregon State Univ, Dept Nutr & Exercise Sci, Linus Pauling Inst, Corvallis, OR 97331 USA.
[Ferrucci, L.] NIA, Longitudinal Studies Branch, Div Clin Res, NIH, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
OI Traber, Maret/0000-0002-2892-4024
FU National Institutes of Health [R01 CA105048, R01 AG027012, R01 AG029148,
R01 HL094507, R37 AG019905]; National Institute on Aging, NIH
FX This study was supported by the National Institutes of Health Grants R01
CA105048, R01 AG027012, R01 AG029148, R01 HL094507 and R37 AG019905, and
the Intramural Research Program, National Institute on Aging, NIH.
NR 28
TC 20
Z9 20
U1 1
U2 18
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 JAN
PY 2012
VL 66
IS 1
BP 3
EP 9
DI 10.1038/ejcn.2011.139
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 876GE
UT WOS:000299094800002
PM 21792213
ER
PT J
AU Anderson, AL
Harris, TB
Tylavsky, FA
Perry, SE
Houston, DK
Lee, JS
Kanaya, AM
Sahyoun, NR
AF Anderson, A. L.
Harris, T. B.
Tylavsky, F. A.
Perry, S. E.
Houston, D. K.
Lee, J. S.
Kanaya, A. M.
Sahyoun, N. R.
CA Hlth ABC Study
TI Dietary patterns, insulin sensitivity and inflammation in older adults
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE diet; dietary patterns; insulin sensitivity; inflammation; older adults
ID LIFE-STYLE INTERVENTION; WAIST CIRCUMFERENCE; METABOLIC SYNDROME;
BODY-MASS; RESISTANCE; GENE; GLUCOSE; MARKERS; INDEX; WOMEN
AB Background/Objectives: Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and to examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation.
Subjects/Methods: The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire. In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis.
Results: Six clusters were identified, including a 'healthy foods' cluster, characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the 'healthy foods' cluster had significantly lower fasting insulin and homeostasis model assessment of insulin resistance values than the 'breakfast cereal' and 'high-fat dairy products' clusters, and lower fasting glucose than the 'high-fat dairy products' cluster (p <= 0.05). No differences were found in 2-h glucose. With respect to inflammation, the 'healthy foods' cluster had lower interleukin-6 than the 'sweets and desserts' and 'high-fat dairy products' clusters, and no differences were seen in C-reactive protein or tumor necrosis factor-a.
Conclusions: A dietary pattern high in low-fat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults. European Journal of Clinical Nutrition (2012) 66, 18-24; doi:10.1038/ejcn.2011.162; published online 14 September 2011
C1 [Anderson, A. L.; Sahyoun, N. R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Harris, T. B.] NIA, NIH, Bethesda, MD 20892 USA.
[Tylavsky, F. A.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Perry, S. E.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Houston, D. K.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
[Lee, J. S.] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA.
[Kanaya, A. M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Anderson, AL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA.
EM amylouiseanderson@yahoo.com
RI Sahyoun, Nadine/G-2608-2011
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA/NIH
FX The Health ABC Study was supported by the National Institute on Aging
(NIA) contracts N01-AG-6-2101, N01-AG-6-2103 and N01-AG-6-2106. This
research was supported in part by the Intramural Research Program of
NIA/NIH.
NR 21
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U1 1
U2 12
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 JAN
PY 2012
VL 66
IS 1
BP 18
EP 24
DI 10.1038/ejcn.2011.162
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 876GE
UT WOS:000299094800004
PM 21915138
ER
PT J
AU Satyanarayana, A
Klarmann, KD
Gavrilova, O
Keller, JR
AF Satyanarayana, Ande
Klarmann, Kimberly D.
Gavrilova, Oksana
Keller, Jonathan R.
TI Ablation of the transcriptional regulator Id1 enhances energy
expenditure, increases insulin sensitivity, and protects against age and
diet induced insulin resistance, and hepatosteatosis
SO FASEB JOURNAL
LA English
DT Article
DE PGC1a; UCP1; adipogenesis; brown adipose tissue; thermogenesis
ID WHITE ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; IN-VIVO; MELANOCORTIN
SYSTEM; HEPATIC STEATOSIS; INDUCED OBESITY; LEAN PHENOTYPE; DEFICIENT
MICE; KNOCKOUT MICE; BROWN FAT
AB Obesity is a major health concern that contributes to the development of diabetes, hyperlipidemia, coronary artery disease, and cancer. Id proteins are helix-loop-helix transcription factors that regulate the proliferation and differentiation of cells from multiple tissues, including adipocytes. We screened mouse tissues for the expression of Id1 and found that Id1 protein is highly expressed in brown adipose tissue (BAT) and white adipose tissue (WAT), suggesting a role for Id1 in adipogenesis and cell metabolism. Id1(-/-) mice are viable but show a significant reduction in fat mass (P<0.005) over the life of the animal that was not due to decreased number of adipocytes. Analysis of Id1(-/-) mice revealed higher energy expenditure, increased lipolysis, and fatty acid oxidation, resulting in reduced triglyceride accumulation in WAT compared to Id1(+/+) mice. Serum levels of triglycerides (193.9 +/- 32.2 vs. 86.5 +/- 33.8, P<0.0005), cholesterol (189.4 +/- 33.8 vs. 110.6 +/- 8.23, P<0.0005) and leptin (1263 +/- 835 vs. 222 +/- 260, P<0.005) were significantly lower in aged Id1(-/-) mice compared to Id1(+/+) mice. Id1-deficient mice have higher resting (P<0.005) and total (P<0.05) O-2 consumption and lower respiratory exchange ratio (P<0.005), confirming that Id1(-/-) mice use a higher proportion of lipid as an energy source for the increased energy expenditure. The expression of PGC1 alpha and UCP1 were 2- to 3-fold up-regulated in Id1(-/-) BAT, suggesting that loss of Id1 increases thermogenesis. As a consequence of higher energy expenditure and reduced fat mass, Id1(-/-) mice displayed enhanced insulin sensitivity. Id1 deficiency protected mice against age-and high-fat-diet-induced adiposity, insulin resistance, and hepatosteatosis. Our findings suggest that Id1 plays a critical role in the regulation of energy homeostasis and could be a potential target in the treatment of insulin resistance and fatty liver disease.-Satyanarayana, A., Klarmann, K. D., Gavrilova, 1 O., Keller, J. R. Ablation of the transcriptional regulator Id1 enhances energy expenditure, increases insulin sensitivity, and protects against age and diet-induced insulin resistance and hepatosteatosis. FASEB J. 26, 309-323 (2012). www.fasebj.org
C1 [Satyanarayana, Ande; Klarmann, Kimberly D.; Keller, Jonathan R.] NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res, Frederick, MD 21701 USA.
[Gavrilova, Oksana] Natl Inst Diabet Digest & Kidney Dis, Mouse Metab Core Lab, NIH, Bethesda, MD USA.
RP Keller, JR (reprint author), Inst Frederick, Basic Res Program, SAIC Frederick, Ctr Canc Res, Bldg 560-12-03,1050 Boyles St, Frederick, MD 21702 USA.
EM kellerjo@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX The authors thank Dr. Robert Benezra (Memorial Sloan-Kettering Cancer
Center, New York, NY, USA) for providing the Id1-knockout mice. The
authors thank Steven Stull and Juanita Mercado for animal care; Tatyana
Chanturiya and William Jou for technical help; and Roberta Smith and the
Pathology/Histotechnology Laboratory, NCI-Frederick, for tissue
sectioning and staining. This research was supported by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research. The authors declare no competing
financial interests.
NR 75
TC 17
Z9 17
U1 0
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD JAN
PY 2012
VL 26
IS 1
BP 309
EP 323
DI 10.1096/fj.11-190892
PG 15
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 877SF
UT WOS:000299202200031
PM 21990377
ER
PT J
AU Csoka, B
Selmeczy, Z
Koscso, B
Nemeth, ZH
Pacher, P
Murray, PJ
Kepka-Lenhart, D
Morris, SM
Gause, WC
Leibovich, SJ
Hasko, G
AF Csoka, Balazs
Selmeczy, Zsolt
Koscso, Balazs
Nemeth, Zoltan H.
Pacher, Pal
Murray, Peter J.
Kepka-Lenhart, Diane
Morris, Sidney M., Jr.
Gause, William C.
Leibovich, S. Joseph
Hasko, Gyoergy
TI Adenosine promotes alternative macrophage activation via A(2A) and A(2B)
receptors
SO FASEB JOURNAL
LA English
DT Article
DE cancer; helminth infection; inflammation; wound healing; obesity
ID HUMAN MAST-CELLS; C/EBP-BETA; IL-10 PRODUCTION; GENE-EXPRESSION;
IFN-GAMMA; TNF-ALPHA; ARGINASE; MECHANISM; INFLAMMATION; INFECTIONS
AB Adenosine has been implicated in suppressing the proinflammatory responses of classically activated macrophages induced by Th1 cytokines. Alternative macrophage activation is induced by the Th2 cytokines interleukin (IL)-4 and IL-13; however, the role of adenosine in governing alternative macrophage activation is unknown. We show here that adenosine treatment of IL-4- or IL-13-activated macrophages augments the expression of alternative macrophage markers arginase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and macrophage galactose-type C-type lectin-1. The stimulatory effect of adenosine required primarily A(2B) receptors because the nonselective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased both arginase activity (EC50 = 261.8 nM) and TIMP-1 production (EC50 = 80.67 nM), and both pharmacologic and genetic blockade of A(2B) receptors prevented the effect of NECA. A(2A) receptors also contributed to the adenosine augmentation of IL-4-induced TIMP-1 release, as both adenosine and NECA were less efficacious in augmenting TIMP-1 release by A(2A) receptor-deficient than control macrophages. Of the transcription factors known to drive alternative macrophage activation, CCAAT-enhancer-binding protein beta was required, while cAMP response element-binding protein and signal transducer and activator of transcription 6 were dispensable in mediating the effect of adenosine. We propose that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation.-Csoka, B., Selmeczy, Z., Koscso, B., Nemeth, Z. H., Pacher, P., Murray, P. J., Kepka-Lenhart, D., Morris S. M., Jr., Gause, W. C., Leibovich, S. J., Hasko, G. Adenosine promotes alternative macrophage activation via A(2A) and A(2B) receptors. FASEB J. 26, 376-386 (2012). www.fasebj.org
C1 [Csoka, Balazs; Selmeczy, Zsolt; Koscso, Balazs; Nemeth, Zoltan H.; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA.
[Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
[Leibovich, S. Joseph] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Cell Biol & Mol Med, Newark, NJ 07103 USA.
[Nemeth, Zoltan H.] Morristown Mem Hosp, Dept Surg, Morristown, NJ USA.
[Pacher, Pal] NIAAA, Bethesda, MD 90034 USA.
[Murray, Peter J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Murray, Peter J.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Kepka-Lenhart, Diane; Morris, Sidney M., Jr.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Hasko, Gyoergy] Univ Debrecen, Dept Med Chem, Med & Hlth Sci Ctr, Debrecen, Hungary.
RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA.
EM haskoge@umdnj.edu
RI Pacher, Pal/B-6378-2008; Morris, Sidney/I-3440-2015;
OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130
FU U.S. National Institutes of Health (NIH) [R01GM66189, R01GM57384]; NIH,
National Institute on Alcohol Abuse and Alcoholism; Hungarian Research
Fund [CK 78275]
FX This work was supported by U.S. National Institutes of Health (NIH)
grants R01GM66189 and R01GM57384, and the NIH Intramural Research
Program, National Institute on Alcohol Abuse and Alcoholism, as well as
the Hungarian Research Fund (CK 78275). The authors declare no competing
financial interests.
NR 57
TC 76
Z9 78
U1 1
U2 13
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD JAN
PY 2012
VL 26
IS 1
BP 376
EP 386
DI 10.1096/fj.11-190934
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 877SF
UT WOS:000299202200037
PM 21926236
ER
PT J
AU Shi, J
Ju, M
Abramowitz, J
Large, WA
Birnbaumer, L
Albert, AP
AF Shi, Jian
Ju, Min
Abramowitz, Joel
Large, William A.
Birnbaumer, Lutz
Albert, Anthony P.
TI TRPC1 proteins confer PKC and phosphoinositol activation on native
heteromeric TRPC1/C5 channels in vascular smooth muscle: comparative
study of wild-type and TRPC1(-/-) mice
SO FASEB JOURNAL
LA English
DT Article
DE Ca2+; signaling; hypertension; transgenic
ID OPERATED CA2+ CHANNELS; CA2+-PERMEABLE CATION CHANNEL; GLOMERULAR
MESANGIAL CELLS; CORONARY-ARTERY MYOCYTES; KINASE-C;
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; ANGIOTENSIN-II; CALCIUM-ENTRY;
DESENSITIZATION; DIACYLGLYCEROL
AB Ca2+-permeable cation channels consisting of canonical transient receptor potential 1 (TRPC1) proteins mediate Ca2+ influx pathways in vascular smooth muscle cells (VSMCs), which regulate physiological and pathological functions. We investigated properties conferred by TRPC1 proteins to native single TRPC channels in acutely isolated mesenteric artery VSMCs from wildtype (WT) and TRPC1-deficient (TRPC1(-/-)) mice using patch-clamp techniques. In WT VSMCs, the intracellular Ca2+ store-depleting agents cyclopiazonic acid (CPA) and 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) both evoked channel currents, which had unitary conductances of similar to 2 pS. In TRPC1(-/-) VSMCs, CPA-induced channel currents had 3 subconductance states of 14, 32, and 53 pS. Passive depletion of intracellular Ca2+ stores activated whole-cell cation currents in WT but not TRPC1(-/-) VSMCs. Differential blocking actions of anti-TRPC antibodies and coimmunoprecipitation studies revealed that CPA induced heteromeric TRPC1/C5 channels in WT VSMCs and TRPC5 channels in TRPC1(-/-) VSMCs. CPA-evoked TRPC1/C5 channel activity was prevented by the protein kinase C (PKC) inhibitor chelerythrine. In addition, the PKC activator phorbol 12,13-dibutyrate (PDBu), a PKC catalytic subunit, and phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidylinositol-3,4,5-trisphosphate (PIP3) activated TRPC1/C5 channel activity, which was prevented by chelerythrine. In contrast, CPA-evoked TRPC5 channel activity was potentiated by chelerythrine, and inhibited by PDBu, PIP2, and PIP3. TRPC5 channels in TRPC1(-/-) VSMCs were activated by increasing intracellular Ca2+ concentrations ([Ca2+](i)), whereas increasing [Ca2+](i) had no effect in WT VSMCs. We conclude that agents that deplete intracellular Ca2+ stores activate native heteromeric TRPC1/C5 channels in VSMCs, and that TRPC1 subunits are important in determining unitary conductance and conferring channel activation by PKC, PIP2, and PIP3.-Shi, J., Ju, M., Abramowitz, J., Large, W. A., Birnbaumer, L., Albert, A. P. TRPC1 proteins confer PKC and phosphoinositol activation on native heteromeric TRPC1/C5 channels in vascular smooth muscle: comparative study of wild-type and TRPC1(-/-) mice. FASEB J. 26, 409-419 (2012). www.fasebj.org
C1 [Shi, Jian; Ju, Min; Large, William A.; Albert, Anthony P.] Univ London, Div Biomed Sci, London SW17 0RE, England.
[Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC USA.
RP Albert, AP (reprint author), Univ London, Div Biomed Sci, London SW17 0RE, England.
EM aalbert@sgul.ac.uk
RI Abramowitz, Joel/A-2620-2015
FU British Heart Foundation
FX This work was supported by the British Heart Foundation.
NR 47
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Z9 28
U1 1
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD JAN
PY 2012
VL 26
IS 1
BP 409
EP 419
DI 10.1096/fj.11-185611
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 877SF
UT WOS:000299202200040
PM 21968068
ER
PT J
AU He, AB
Shen, XH
Ma, Q
Cao, JJ
von Gise, A
Zhou, PZ
Wang, G
Marquez, VE
Orkin, SH
Pu, WT
AF He, Aibin
Shen, Xiaohua
Ma, Qing
Cao, Jingjing
von Gise, Alexander
Zhou, Pingzhu
Wang, Gang
Marquez, Victor E.
Orkin, Stuart H.
Pu, William T.
TI PRC2 directly methylates GATA4 and represses its transcriptional
activity
SO GENES & DEVELOPMENT
LA English
DT Article
DE epigenetics; heart development; polycomb complex; transcriptional
regulation
ID HISTONE METHYLTRANSFERASE ACTIVITY; H3 LYSINE-27 METHYLATION;
STEM-CELLS; POLYCOMB; EZH2; DIFFERENTIATION; ACETYLATION; PROTEIN;
GENOME; HEART
AB Polycomb-repressive complex 2 (PRC2) promotes tissue-specific differentiation by depositing trimethylated histone H3 Lys 27 (H3K27me3) epigenetic marks to silence ectopic gene expression programs. Here, we show that EZH2, the catalytic subunit of PRC2, is required for cardiac morphogenesis. Both in vitro and in fetal hearts, EZH2 interacted with cardiac transcription factor GATA4 and directly methylated it at Lys 299. PRC2 methylation of GATA4 attenuated its transcriptional activity by reducing its interaction with and acetylation by p300. Our results reveal a new mechanism of PRC2-mediated transcriptional repression in which PRC2 methylates a transcription factor to inhibit its transcriptional activity.
C1 [He, Aibin; Ma, Qing; Cao, Jingjing; von Gise, Alexander; Zhou, Pingzhu; Wang, Gang; Pu, William T.] Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp Boston, Boston, MA 02115 USA.
[He, Aibin; Shen, Xiaohua; Ma, Qing; Cao, Jingjing; von Gise, Alexander; Zhou, Pingzhu; Wang, Gang; Orkin, Stuart H.; Pu, William T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Shen, Xiaohua; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp Boston, Boston, MA 02115 USA.
[Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Pu, WT (reprint author), Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp Boston, Boston, MA 02115 USA.
EM wpu@enders.tch.harvard.edu
RI Zhou, Pingzhu/J-2809-2014
FU National Institutes of Health (NIH) [U01HL098166, R01HL095712]; American
Heart Association; NIDDK; NIH, National Cancer Institute, and Center for
Cancer Research
FX This work was supported by funding from the National Institutes of
Health (NIH) (U01HL098166 and R01HL095712 to W.T.P.) and the American
Heart Association (post-doctoral fellowship to A. H.); by charitable
donations from Edward Marram, Karen Carpenter, and Gail Federici Smith;
and by a Center of Excellence Award in Molecular Hematology from the
NIDDK to S.H.O., an Investigator of the HHMI. This research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, and Center for Cancer Research. Mass
spectrometry analysis was performed by the Proteomics Center at
Children's Hospital Boston.
NR 34
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U1 4
U2 24
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 JAN 1
PY 2012
VL 26
IS 1
BP 37
EP 42
DI 10.1101/gad.173930.111
PG 6
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 877RI
UT WOS:000299199200006
PM 22215809
ER
PT J
AU Edwards, DRV
Baird, DD
Hasan, R
Savitz, DA
Hartmann, KE
AF Edwards, D. R. Velez
Baird, D. D.
Hasan, R.
Savitz, D. A.
Hartmann, K. E.
TI First-trimester bleeding characteristics associate with increased risk
of preterm birth: data from a prospective pregnancy cohort
SO HUMAN REPRODUCTION
LA English
DT Article
DE epidemiology; first-trimester; pregnancy; preterm birth; vaginal
bleeding
ID BACTERIAL VAGINOSIS; 1ST TRIMESTER; DELIVERY; WOMEN; METAANALYSIS;
POPULATION; BIAS
AB BACKGROUND: Prior evidence linking first-trimester bleeding with preterm birth (PTB, <37 weeks gestation) risk has been inconsistent and may be biased by subject selection and/or incomplete documentation of bleeding episodes for all participants. Prior studies have not carefully examined the role of bleeding characteristics in PTB risk. In the present study, we estimate the association between first-trimester bleeding and PTB in a non-clinical prospective cohort and test whether bleeding characteristics better predict risk.
METHODS: Women were enrolled in Right from the Start (2000-2009), a prospective pregnancy cohort. Data about bleeding and bleeding characteristics were examined with logistic regression to assess association with PTB.
RESULTS: Among 3978 pregnancies 344 were PTB and 3634 term. Bleeding was reported by 986 (26%) participants. After screening candidate confounders, only multiple gestations remained in the model. Bleeding associated with PTB [odds ratio (OR)(adjusted) = 1.40, 95% confidence interval (CI) 1.09-1.80]. Risk did not vary by race/ethnicity. Compared with non-bleeders, PTB risk was higher for bleeding with red color (OR(adjusted) = 1.92, 95% CI, 1.32-2.82), for heavy episodes (OR(adjusted) = 2.40, 95% CI 1.18-4.88) and long duration (OR(adjusted) = 1.67, 95% CI 1.17-2.38).
CONCLUSIONS: Bleeding associated with PTB was not confounded by common risk factors for bleeding or PTB. PTB risk was greatest for women with heavy bleeding episodes with long duration and red color and would suggest that combining women with different bleeding characteristics may affect the accuracy of risk assessment. These data suggest a candidate etiologic pathway for PTB and warrant further investigation of the biologic mechanisms.
C1 [Edwards, D. R. Velez; Hartmann, K. E.] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
[Edwards, D. R. Velez] Ctr Human Genet Res, Nashville, TN 37232 USA.
[Baird, D. D.] NIEHS, Epidemiol Branch, NIH, Durham, NC 27707 USA.
[Hasan, R.] Univ N Carolina Gillings, Dept Epidemiol, Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Savitz, D. A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Savitz, D. A.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
RP Edwards, DRV (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
EM digna.r.velez.edwards@vanderbilt.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Child and Human Development [R01HD043883,
R01HD049675]; American Water Association Research Foundation [2579];
Building Interdisciplinary Research Careers in Women's Health career
development program [K12HD4383]; National Institute of Environmental
Health Sciences, NIH
FX The authors acknowledge the field research was supported by grants from
the National Institute of Child and Human Development (R01HD043883 and
R01HD049675) and the American Water Association Research Foundation
(2579). Additional funds were provided by the Building Interdisciplinary
Research Careers in Women's Health career development program
(K12HD4383). This research was funded in part (DD Baird salary) by the
National Institute of Environmental Health Sciences, NIH.
NR 39
TC 5
Z9 5
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JAN
PY 2012
VL 27
IS 1
BP 54
EP 60
DI 10.1093/humrep/der354
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 877ZG
UT WOS:000299220600009
ER
PT J
AU Amarnath, S
Fowler, DH
AF Amarnath, Shoba
Fowler, Daniel H.
TI Harnessing autophagy for adoptive T-cell therapy
SO IMMUNOTHERAPY
LA English
DT Editorial Material
DE autophagy; immunology; rapamycin; Th1; Th2; transplantation; tumor
ID DONOR TH2 CELLS; MAMMALIAN TARGET; IN-VIVO; DISEASE; APOPTOSIS;
SURVIVAL; TH1/TC1; COMPLEX; PREVENT; MEMORY
C1 [Amarnath, Shoba; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Amarnath, S (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr, 3 E Labs,3-3224, Bethesda, MD 20892 USA.
EM samarnath@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 26
TC 5
Z9 5
U1 0
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD JAN
PY 2012
VL 4
IS 1
BP 1
EP 4
DI 10.2217/IMT.11.144
PG 4
WC Immunology
SC Immunology
GA 878EH
UT WOS:000299236700001
PM 22149992
ER
PT J
AU Goncalves, AN
Meschiari, CA
Stetler-Stevenson, WG
Nonato, MC
Alves, CP
Espreafico, EM
Gerlach, RF
AF Goncalves, Andrezza N.
Meschiari, Cesar A.
Stetler-Stevenson, William G.
Nonato, M. Cristina
Alves, Cleidson P.
Espreafico, Enilza M.
Gerlach, Raquel F.
TI Expression of soluble and functional full-length human matrix
metalloproteinase-2 in Escherichia coli
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Article
DE Matrix metalloproteinase-2; Gelatinase A; Bacteria; Protein expression;
Escherichia coli
ID GELATINASE-A; IV COLLAGENASE; TISSUE INHIBITOR; MMP-2; ACTIVATION;
BINDING; DOMAIN; PURIFICATION; FIBROBLASTS; DYSFUNCTION
AB Characterization of the matrix metalloproteinase-2 (MMP-2) substrates and understanding of its function remain difficult because up to date preparations containing minor amounts of other eukaryotic proteins that are co-purified with MMP-2 are still used. In this work, the expression of a soluble and functional full-length recombinant human MMP-2 (rhMMP-2) in the cytoplasm of Escherichia coli is reported, and the purification of this metalloproteinase is described. Culture of this bacterium at 18 degrees C culminated in maintenance of the soluble and functional rhMMP-2 in the soluble fraction of the E. coli lysate and its purification by affinity with gelatin-sepharose yielded approximately 0.12 mg/L of medium. Western Blotting and zymographic analysis revealed that the most abundant form was the 72-kDa MMP-2, but some gelatinolytic bands corresponding to proteins with lower molecular weight were also detected. The obtained rhMMP-2 was demonstrated to be functional in a gelatinolytic fluorimetric assay, suggesting that the purified rhMMP-2 was correctly folded. The method described here involves fewer steps, is less expensive, and is less prone to contamination with other proteinases and MMP inhibitors as compared to expression of rhMMP-2 in eukaryotic tissue culture. This protocol will facilitate the use of the full-length rhMMP-2 expressed in bacteria and will certainly help researchers to acquire new knowledge about the substrates and biological activities of this important proteinase. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Goncalves, Andrezza N.] Univ Sao Paulo, Dept Pharmaceut Sci, Fac Pharmaceut Sci Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
[Meschiari, Cesar A.] Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
[Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Nonato, M. Cristina] Univ Sao Paulo, Dept Chem & Phys, Fac Pharmaceut Sci Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
[Alves, Cleidson P.; Espreafico, Enilza M.] Univ Sao Paulo, Dept Mol & Cellular Biol, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
[Gerlach, Raquel F.] Univ Sao Paulo, Dept Morphol Stomatol & Physiol, Dent Sch Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
RP Gerlach, RF (reprint author), FORP USP, Fac Odontol Ribeirao Preto, Avenida Cafe S-N, BR-14040904 Ribeirao Preto, SP, Brazil.
EM rfgerlach@forp.usp.br
RI Nonato, Maria/C-5659-2012; Gerlach, Raquel/D-7883-2012;
Stetler-Stevenson, William/H-6956-2012; Espreafico, Enilza/O-3053-2016
OI Stetler-Stevenson, William/0000-0002-5500-5808;
FU State of Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do
Estado de Sao Paulo, FAPESP)
FX This study was funded by the State of Sao Paulo Research Foundation
(Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP). We thank
Dr. Jose Moacyr Marin for allocation of equipment and technical
discussions.
NR 32
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U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
J9 J BIOTECHNOL
JI J. Biotechnol.
PD JAN
PY 2012
VL 157
IS 1
BP 20
EP 24
DI 10.1016/j.jbiotec.2011.09.030
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 869YB
UT WOS:000298635200004
PM 22001844
ER
PT J
AU Valenzuela, MS
Hu, L
Lueders, J
Walker, R
Meltzer, PS
AF Valenzuela, Manuel S.
Hu, Lan
Lueders, John
Walker, Robert
Meltzer, Paul S.
TI Broader utilization of origins of DNA replication in cancer cell lines
along a 78?kb region of human chromosome 2q34
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE DNA replication origins; Nascent DNA; Real-time PCR; Human cell lines;
RPE gene
ID TRANSFORMED MAMMALIAN-CELLS; INITIATION POINTS; S PHASE; SITES;
IDENTIFICATION; SUBUNITS; STRESS; CHOICE
AB Human DNA replication depends on the activation of thousands of origins distributed within the genome. The actual distribution of origins is not known, nor whether this distribution is unique to a cell type, or if it changes with the proliferative state of the cell. In this study, we have employed a real-time PCR-based nascent strand DNA abundance assay, to determine the location of origins along a 78 kb region on Chr2q34. Preliminary studies using nascent DNA strands isolated from either HeLa and normal skin fibroblast cells showed that in both cell lines peaks of high origin activity mapped in similar locations. However, the overall origin profile in HeLa cells corresponded to broad origin activation zones, whereas in fibroblasts a more punctuated profile of origin activation was observed. To investigate the relevance of this differential origin profile, we compared the origin distribution profiles in breast cancer cell lines MDA-MB-231, BT-474, and MCF-7, to their normal counterpart MCF-10A. In addition, the CRL7250 cell line was also used as a normal control. Our results validated our earlier observation and showed that the origin profile in normal cell lines exhibited a punctuated pattern, in contrast to broader zone profiles observed in the cancer cell lines. A quantitative analysis of origin peaks revealed that the number of activated origins in cancer cells is statistically larger than that obtained in normal cells, suggesting that the flexibility of origin usage is significantly increased in cancer cells compared to their normal counterparts. J. Cell. Biochem. 113: 132140, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Valenzuela, Manuel S.; Hu, Lan] Meharry Med Coll, Sch Med, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
[Lueders, John; Walker, Robert; Meltzer, Paul S.] NCI, Genet Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Valenzuela, MS (reprint author), Meharry Med Coll, Sch Med, Dept Biochem & Canc Biol, 1005 DB Todd Jr,Blvd, Nashville, TN 37208 USA.
EM mvalenzuela@mmc.edu
FU National Institute for Human Genome Research; National Institutes of
Health (NIH) [CA138180]
FX We would like to thank S. Anderson, and M. Kirby, for assistance with
the flow cytometry studies, and to Nicole Green and Yidong Chen for help
with the figures. MSV wishes to thank the Health Disparities Visiting
Faculty Program at the National Institute for Human Genome Research for
support during the initial phase of this study. This research was funded
in part by the intramural program of the National Institutes of Health
(NIH), and by NIH grant CA138180 to MSV.
NR 24
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U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JAN
PY 2012
VL 113
IS 1
BP 132
EP 140
DI 10.1002/jcb.23336
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 869LB
UT WOS:000298598300015
PM 21898540
ER
PT J
AU O'Shea, TM
Allred, EN
Kuban, KCK
Hirtz, D
Specter, B
Durfee, S
Paneth, N
Leviton, A
AF O'Shea, T. Michael
Allred, Elizabeth N.
Kuban, Karl C. K.
Hirtz, Deborah
Specter, Barbara
Durfee, Sara
Paneth, Nigel
Leviton, Alan
CA ELGAN Study Investigators
TI Intraventricular Hemorrhage and Developmental Outcomes at 24 Months of
Age in Extremely Preterm Infants
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE cerebral palsy; vision impairment; developmental delay; disability;
prematurity; Bayley Scales of Infant Development; neurodevelopmental
outcome; intraventricular hemorrhage
ID LOW-BIRTH-WEIGHT; ULTRASOUND ABNORMALITIES; CEREBRAL-PALSY; CHILDREN;
DISORDERS; BRAIN; PREMATURITY; DISABILITY; COHORT
AB Whether intraventricular hemorrhage increases the risk of adverse developmental outcome among premature infants is controversial. Using brain ultrasound, we identified intraventricular hemorrhage and white matter abnormalities among 1064 infants born before 28 weeks' gestation. We identified adverse developmental outcomes at 24 months of age using a standardized neurologic examination and the Bayley Scales of Infant Development Mental and Motor Scales. In logistic regression models that adjusted for gestational age, sex, and public insurance, isolated intraventricular hemorrhage was associated with visual fixation difficulty but no other adverse outcome. Infants who had a white matter lesion unaccompanied by intraventricular hemorrhage were at increased risk of cerebral palsy, low Mental and Motor Scores, and visual and hearing impairments. Except when accompanied or followed by a white matter lesion, intraventricular hemorrhage is associated with no more than a modest increase (and possibly no increase) in the risk of adverse developmental outcome during infancy.
C1 [O'Shea, T. Michael; Specter, Barbara] Wake Forest Sch Med, Winston Salem, NC USA.
[Allred, Elizabeth N.; Durfee, Sara; Leviton, Alan] Harvard Univ, Sch Med, Boston, MA USA.
[Allred, Elizabeth N.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Allred, Elizabeth N.; Leviton, Alan] Childrens Hosp, Boston, MA 02115 USA.
[Kuban, Karl C. K.] Boston Med Ctr, Dept Pediat, Boston, MA USA.
[Hirtz, Deborah] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Paneth, Nigel] Michigan State Univ, E Lansing, MI 48824 USA.
RP O'Shea, TM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
EM moshea@wfubmc.edu
OI Kuban, Karl/0000-0001-5299-3567
FU National Institute of Neurological Diseases and Stroke
[5U01NS040069-05]; National Institute of Child Health and Human
Development [5P30HD018655-28]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This study was
supported by a cooperative agreement with the National Institute of
Neurological Diseases and Stroke (5U01NS040069-05) and a program project
grant from the National Institute of Child Health and Human Development
(5P30HD018655-28).
NR 29
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U1 2
U2 16
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD JAN
PY 2012
VL 27
IS 1
BP 22
EP 29
DI 10.1177/0883073811424462
PG 8
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 873LP
UT WOS:000298885100004
PM 22232137
ER
PT J
AU Nakamura, EF
Cui, LH
Lateef, T
Nelson, KB
Merikangas, KR
AF Nakamura, Erin F.
Cui, Lihong
Lateef, Tarannum
Nelson, Karin B.
Merikangas, Kathleen R.
TI Parent-Child Agreement in the Reporting of Headaches in a National
Sample of Adolescents
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE headache; migraine; concordance; National Comorbidity Survey-Adolescent
Supplement
ID SUPPLEMENT NCS-A; UNITED-STATES; YOUNG-ADULTS; MIGRAINE; COMORBIDITY;
IMPACT; PREVALENCE; HEALTH; SCHOOLCHILDREN; ASSOCIATION
AB The aim of this article is to assess the concordance between parent and adolescent headache ratings in a representative sample of 6483 US adolescents (aged 13-18 years). Headaches were assessed using modified criteria from the International Headache Society's International Classification of Headache Disorders, Second Edition. Caregiver report was based on a self-administered questionnaire. Overall concordance between caregivers and adolescents on the presence or absence of headaches was quite low (kappa = 0.39). Female caregivers were twice as likely as male caregivers to report headaches in their offspring. Positive endorsement of headaches in offspring by caregivers was associated with adolescent-reported chronic headaches, longer headache duration, and photophobia or phonophobia. These findings suggest that relying solely on parent report may result in an underestimate of the true prevalence of headaches in the general population. In addition, collecting information from both parents and adolescents could be critical to effective treatment and prevention of the severe consequences of migraine.
C1 [Nakamura, Erin F.; Cui, Lihong; Lateef, Tarannum; Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20814 USA.
[Lateef, Tarannum; Nelson, Karin B.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Nelson, Karin B.] NINDS, Intramural Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Nakamura, EF (reprint author), NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bldg 35,Room 1A112,35 Convent Dr,MSC 3720, Bethesda, MD 20814 USA.
EM nakamurae@mail.nih.gov
FU National Institute of Mental Health [Z01 MH002808-08, U01-MH60220];
National Comorbidity Survey-Adolescent Supplement
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: This work was supported by
the Intramural Research Program of the National Institute of Mental
Health (Z01 MH002808-08), the National Comorbidity Survey-Adolescent
Supplement, and the larger program of related National Combordity
Surveys by the National Institute of Mental Health (U01-MH60220).
NR 48
TC 11
Z9 11
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD JAN
PY 2012
VL 27
IS 1
BP 61
EP 67
DI 10.1177/0883073811413580
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 873LP
UT WOS:000298885100009
PM 21832254
ER
PT J
AU Betancourt, L
Rada, P
Paredes, D
Hernandez, L
AF Betancourt, Luis
Rada, Pedro
Paredes, Daniel
Hernandez, Luis
TI In vivo monitoring of cerebral agmatine by microdialysis and capillary
electrophoresis
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Capillary electrophoresis; Neurotransmission; Chemical messengers;
Bioamines; Probe recovery
ID CLONIDINE-DISPLACING SUBSTANCE; PERFORMANCE LIQUID-CHROMATOGRAPHY;
INDUCED FLUORESCENCE DETECTION; BIOGENIC-AMINES; IMIDAZOLINE RECEPTORS;
RAT-BRAIN; EXTRACELLULAR GLUTAMATE; DECARBOXYLATED ARGININE;
HIPPOCAMPAL-NEURONS; BIOLOGICAL SAMPLES
AB Agmatine is a putative neurotransmitter in the brain. Current analytical techniques do not allow the detection of agmatine in extracellular fluid, making it difficult to study its physiological role. However, a new method for in vivo monitoring agmatine in the brain was developed. Capillary zone electrophoresis and laser induced fluorescence detection (CZE-LIFD) was used to measure nanomolar concentrations of agmatine in submicroliter sample volumes. This analytical technique proved to detect 0.49 attomole of agmatine improving the sensitivity of previous analytical techniques. On the other hand, the hippocampus is a brain region well known for having a population of agmatine containing neurons. Therefore, intracerebral microdialysis was performed in the hippocampus and agmatine was extracted from the extracellular environment. Detectable amounts of agmatine were found in dialysates from probes located in the hippocampus but not from the probes located in the lateral ventricle. Furthermore, extracellular agmatine was calcium and impulse dependent and depolarization of hippocampal neurons increased extracellular agmatine concentration. The methods reported here are sensitive enough to study the physiological role of brain agmatine in freely moving animals. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Betancourt, Luis] Univ Los Andes, Fac Med, Dept Morphol Sci, Sch Med, Merida 5101, Venezuela.
[Betancourt, Luis; Rada, Pedro; Hernandez, Luis] Univ Los Andes, Dept Physiol, Sch Med, Merida 5101, Venezuela.
[Paredes, Daniel] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Betancourt, L (reprint author), Univ Los Andes, Fac Med, Dept Morphol Sci, Sch Med, Ave Don Tulio, Merida 5101, Venezuela.
EM betahitcher@gmail.com
RI Paredes , Daniel/L-6610-2013
FU CDCHT [M-1000-10-03-B, M-967-080-7-F]
FX This research was supported by Grants M-1000-10-03-B and M-967-080-7-F
from the CDCHT.
NR 64
TC 4
Z9 5
U1 9
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD JAN 1
PY 2012
VL 880
BP 58
EP 65
DI 10.1016/j.jchromb.2011.11.016
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 877QS
UT WOS:000299197600009
PM 22134038
ER
PT J
AU Peer, CJ
Spencer, SD
VanDenBerg, DAH
Pacanowski, MA
Horenstein, RB
Figg, WD
AF Peer, Cody J.
Spencer, Shawn D.
VanDenBerg, Dustin A. H.
Pacanowski, Michael A.
Horenstein, Richard B.
Figg, William D.
TI A sensitive and rapid ultra HPLC-MS/MS method for the simultaneous
detection of clopidogrel and its derivatized active thiol metabolite in
human plasma
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Clopidogrel; Active metabolite; Ultra HPLC-MS/MS
ID CARBOXYLIC-ACID METABOLITE; CHROMATOGRAPHY/TANDEM MASS-SPECTROMETRY;
LC-MS/MS; PHARMACOKINETICS; QUANTIFICATION; POLYMORPHISMS; VALIDATION;
PRASUGREL; MS
AB A sensitive, selective, and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (uHPLC-MS/MS) was developed for the simultaneous quantification of clopidogrel (Plavix (R)) and its derivatized active metabolite (CAMD) in human plasma. Derivatization of the active metabolite in blood with 2-bromo-3'-methoxy acetophenone (MPB) immediately after collection ensured metabolite stability during sample handling and storage. Following addition of ticlopidine as an internal standard and simple protein precipitation, the analytes were separated on a Waters Acquity UPLC (TM) sub-2 mu m-C(18) column via gradient elution before detection on a triple-quadrupole MS with multiple-reaction-monitoring via electrospray ionization. The method was validated across the clinically relevant concentration range of 0.01-50 ng/mL for parent clopidogrel and 0.1-150 ng/mL (r(2) =0.99) for CAMD, with a fast run time of 1.5 min to support pharmacokinetic studies using 75, 150, or 300 mg oral doses of clopidogrel. The analytical method measured concentrations of clopidogrel and CAMD with accuracy (%DEV) <+/- 12% and precision (%CV) of <+/- 6%. The method was successfully applied to measure the plasma concentrations of clopidogrel and CAMD in three subjects administered single oral doses of 75, 150, and 300 mg clopidogrel. It was further demonstrated that the derivatizing agent (MPB) does not affect clopidogrel levels, thus from one aliquot of blood drawn clinically, this method can simultaneously quantify both clopidogrel and CAMD with sensitivity in the picogram per mL range. Published by Elsevier B.V.
C1 [Peer, Cody J.; VanDenBerg, Dustin A. H.; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA.
[Spencer, Shawn D.] SAIC Frederick Inc, Appl & Dev Res, NCI, Frederick, MD USA.
[Pacanowski, Michael A.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
[Horenstein, Richard B.] Univ Maryland, Div Endocrinol Diabet & Nutr, Sch Med, Baltimore, MD 21201 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Off Clin Director, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wf13e@nih.gov
RI Figg Sr, William/M-2411-2016
FU National Institutes of Health [128475]; National Institute of General
Medicine Science [U01GM074518-05S1]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This study was funded by the Bench to Bedside Program of the National
Institutes of Health (128475) and the National Institute of General
Medicine Science (U01GM074518-05S1).; 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.
NR 24
TC 28
Z9 32
U1 2
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD JAN 1
PY 2012
VL 880
BP 132
EP 139
DI 10.1016/j.jchromb.2011.11.029
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 877QS
UT WOS:000299197600019
PM 22169056
ER
PT J
AU Moody, TW
Leyton, J
Jensen, RT
AF Moody, Terry W.
Leyton, Julius
Jensen, Robert T.
TI Pituitary Adenylate Cyclase-Activating Polypeptide Causes Increased
Tyrosine Phosphorylation of Focal Adhesion Kinase and Paxillin
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE PACAP; Signal transduction; Tyrosine phosphorylation; FAK; Paxillin;
Lung cancer
ID CELL LUNG-CANCER; VASOACTIVE-INTESTINAL-PEPTIDE;
GASTRIN-RELEASING-PEPTIDE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION;
SPLICE VARIANTS; MESSENGER-RNAS; PROTEIN-KINASE; GROWTH-FACTORS; STRESS
FIBERS
AB The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin were investigated using lung cancer cells. Addition of PACAP-27 or PACAP-38 but not vasoactive intestinal peptide to NCI-H838 or NCI-H1299 human lung cancer cells significantly increased the tyrosine phosphorylation of FAK or paxillin. The increase in FAK or paxillin tyrosine phosphorylation caused by addition of PACAP-27 to NCI-H838 cells was inhibited by PACAP(6-38), a PAC1-receptor (R) antagonist. The increase in FAK or paxillin tyrosine phosphorylation caused by 100 nM PACAP-27 was maximal 2 min after addition to NCI-H838 cells. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by cytochalasin D and genistein which inhibit actin polymerization and tyrosine kinase activity, respectively. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by U-73122 but not H89 which inhibit phospholipase C and protein kinase A, respectively. The results show that PAC1-R regulates FAK and paxillin tyrosine phosphorylation in lung cancer cells as a result of increased phosphatidylinositol turnover but not adenylyl cylase stimulation.
C1 [Moody, Terry W.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Leyton, Julius; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Ctr Canc Res, 31 Ctr Dr,Bldg 31,Rm 4A48, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
FU NCI; NIDDK of NIH
FX This research is supported in part by intramural funds of the NCI and
NIDDK of NIH.
NR 51
TC 3
Z9 3
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD JAN
PY 2012
VL 46
IS 1
BP 68
EP 74
DI 10.1007/s12031-011-9639-7
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 879MA
UT WOS:000299332200008
PM 21898124
ER
PT J
AU Holighaus, Y
Weihe, E
Eiden, LE
AF Holighaus, Yvonne
Weihe, Eberhard
Eiden, Lee E.
TI STC1 Induction by PACAP is Mediated Through cAMP and ERK1/2 but not PKA
in Cultured Cortical Neurons
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE PACAP; cAMP; PKA; ERK; STC1 gene induction; Signaling
ID CYCLASE-ACTIVATING POLYPEPTIDE; CEREBELLAR GRANULE NEURONS;
VASOACTIVE-INTESTINAL-PEPTIDE; PROTEIN-KINASE-A; INDEPENDENT SIGNALING
PATHWAY; FOCAL CEREBRAL-ISCHEMIA; IN-SITU HYBRIDIZATION;
ADENYLATE-CYCLASE; SPLICE VARIANTS; CYCLIC-AMP
AB The neuroprotective actions of PACAP (pituitary adenylate cyclase-activating polypeptide) in vitro and in vivo suggest that activation of its cognate G protein-coupled receptor PAC1 or downstream signaling molecules, and thus activation of PACAP target genes, could be of therapeutic benefit. Here, we show that cultured rat cortical neurons predominantly expressed the PAC1hop and null variants. PACAP receptor activation resulted in the elevation of the two second messengers cAMP and Ca2+ and expression of the putative neuroprotectant stanniocalcin 1 (STC1). PACAP signaling to the STC1 gene proceeded through the extracellular signal-regulated kinases 1 and 2 (ERK1/2), but not through the cAMP-dependent protein kinase (PKA), and was mimicked by the adenylate cyclase activator forskolin. PACAP- and forskolin-mediated activation of ERK1/2 occurred through cAMP, but not PKA. These results suggest that STC1 gene induction proceeds through cAMP and ERK1/2, independently of PKA, the canonical cAMP effector. In contrast, PACAP signaling to the BDNF gene proceeded through PKA, suggesting that two different neuroprotective cAMP pathways co-exist in differentiated cortical neurons. The selective activation of a potentially neuroprotective cAMP-dependent pathway different from the canonical cAMP pathway used in many physiological processes, such as memory storage, has implications for pharmacological activation of neuroprotection in vivo.
C1 [Holighaus, Yvonne; Eiden, Lee E.] Lab Cellular & Mol Regulat, Sect Mol Neurosci, Natl Inst Mental Hlth, Bethesda, MD 20892 USA.
[Weihe, Eberhard] Univ Marburg, Inst Anat & Cell Biol, Marburg, Germany.
RP Eiden, LE (reprint author), Lab Cellular & Mol Regulat, Sect Mol Neurosci, Natl Inst Mental Hlth, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU NIMH [Z01 MH002386-22]
FX We would like to thank Chang-Mei Hsu and Charisse Winston for the expert
technical assistance with the preparation of rat cortical cultures. This
work was supported by NIMH Intramural Research Program Project Z01
MH002386-22.
NR 101
TC 7
Z9 7
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
EI 1559-1166
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD JAN
PY 2012
VL 46
IS 1
BP 75
EP 87
DI 10.1007/s12031-011-9653-9
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 879MA
UT WOS:000299332200009
PM 21975601
ER
PT J
AU Choi, SH
Aid, S
Kim, HW
Jackson, SH
Bosetti, F
AF Choi, Sang-Ho
Aid, Saba
Kim, Hyung-Wook
Jackson, Sharon H.
Bosetti, Francesca
TI Inhibition of NADPH oxidase promotes alternative and anti-inflammatory
microglial activation during neuroinflammation
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE alternative activation; Alzheimer's disease; microglia; NADPH oxidase;
neuroinflammation
ID ALZHEIMERS-DISEASE; INFLAMMATORY RESPONSE; OXIDATIVE STRESS;
GENE-EXPRESSION; BRAIN; MICE; LIPOPOLYSACCHARIDE; HIPPOCAMPUS; INJURY;
MODEL
AB Like macrophages, microglia are functionally polarized into different phenotypic activation states, referred as classical and alternative. The balance of the two phenotypes may be critical to ensure proper brain homeostasis, and may be altered in brain pathological states, such as Alzheimers disease. We investigated the role of NADPH oxidase in microglial activation state using p47phox and gp91phox-deficient mice as well as apocynin, a NADPH oxidase inhibitor during neuroinflammation induced by an intracerebroventricular injection of LPS or A beta 142. We showed that NADPH oxidase plays a critical role in the modulation of microglial phenotype and subsequent inflammatory response. We demonstrated that inhibition of NADPH oxidase or gene deletion of its functional p47phox subunit switched microglial activation from a classical to an alternative state in response to an inflammatory challenge. Moreover, we showed a shift in redox state towards an oxidized milieu and that subpopulations of microglia retain their detrimental phenotype in Alzheimers disease brains. Microglia can change their activation phenotype depending on NADPH oxidase-dependent redox state of microenvironment. Inhibition of NADPH oxidase represents a promising neuroprotective approach to reduce oxidative stress and modulate microglial phenotype towards an alternative state.
C1 [Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Jackson, Sharon H.] NIAID, Monocyte Trafficking Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM sjackson@niaid.nih.gov; frances@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX We acknowledge the Harvard Brain Tissue Resource Center (McLean
Hospital, Belmont, MA) and Dr J.S. Rao (NIA, NIH) for providing human
tissue samples, and Dr S.H. Park (NINDS, NIH) for assistance with
confocal microscopy. This work was supported by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health.
NR 33
TC 76
Z9 79
U1 2
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JAN
PY 2012
VL 120
IS 2
BP 292
EP 301
DI 10.1111/j.1471-4159.2011.07572.x
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 869ME
UT WOS:000298601400011
PM 22050439
ER
PT J
AU Kong, H
Lee, Y
Kim, H
Hong, S
Kim, DD
Yoon, JH
Jung, Y
Kim, YM
AF Kong, Hyesik
Lee, Yonghyun
Kim, Hyunjeong
Hong, Sungchae
Kim, Dae-Duk
Yoon, Jeong-Hyun
Jung, Yunjin
Kim, Young Mi
TI Susceptibility of glucocorticoids to colonic metabolism and
pharmacologic intervention in the metabolism: implication for
therapeutic activity of colon-specific glucocorticoid 21-sulfate sodium
at the target site
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
DE colon-specific drug delivery; glucocorticoid; inflammatory bowel
disease; sulfated glucocorticoid
ID INFLAMMATORY BOWEL-DISEASE; POTENTIAL PRODRUGS; DRUG-DELIVERY; RAT
AB Objectives The systemic side effects of glucocorticoids have prevented their long-term use for treatment of inflammatory bowel disease. Colon-specific delivery of glucocorticoids has been adopted as a strategy to circumvent the toxicological trouble. Glucocorticoids delivered to the large intestine might undergo metabolisms by colonic microflora, which should affect therapeutic availability at the target site. It was investigated whether the susceptibility of glucocorticoids to the colonic metabolisms and pharmacologic intervention in the metabolism could modulate the therapeutic availability of colon-targeted glucocorticoids.
Methods Various glucocorticoids and their derivatives, glucocorticoid 21-sulfate sodium compounds, were incubated in the cecal contents in the presence or absence of reduction inhibitors and the change in the levels of the drugs was monitored.
Key findings The accumulation profiles of the corresponding glucocorticoids liberated from glucocorticoid 21-sulfate sodium compounds vary, depending on the metabolic susceptibility of glucocorticoids. Reduction inhibitors prevented the cecal metabolisms of glucocorticoids, which was most prominent for prednisolone (PD) and methylprednisolone (MP). Moreover, reduction inhibitors increased the accumulated amount of MP and PD released from PD- and MP-21-sulfate sodium in the cecal contents.
Conclusions Our data provide information useful for selection of a glucocorticoid and a pharmacologic strategy for the design of an efficient colon-specific glucocorticoid prodrug.
C1 [Lee, Yonghyun; Kim, Hyunjeong; Hong, Sungchae; Yoon, Jeong-Hyun; Jung, Yunjin; Kim, Young Mi] Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
[Kim, Dae-Duk] Seoul Natl Univ, Coll Pharm, Seoul, South Korea.
[Kim, Dae-Duk] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea.
[Kong, Hyesik] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Jung, Y (reprint author), Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
EM jungy@pusan.ac.kr; ymikim@pusan.ac.kr
RI Kim, Dae Duk/D-8864-2013
FU Korea Research Foundation (KRF); Korean government (MEST)
[KRF-2007-314-E00245, KRF-2008-314-E00315]
FX This work was supported by Korea Research Foundation (KRF) grants funded
by the Korean government (MEST) (KRF-2007-314-E00245 and
KRF-2008-314-E00315).
NR 19
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3573
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD JAN
PY 2012
VL 64
IS 1
BP 128
EP 138
DI 10.1111/j.2042-7158.2011.01386.x
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 861ID
UT WOS:000298011700015
PM 22150680
ER
PT J
AU Gelber, RP
Petrovitch, H
Masaki, KH
Abbott, RD
Ross, GW
Launer, LJ
White, LR
AF Gelber, Rebecca P.
Petrovitch, Helen
Masaki, Kamal H.
Abbott, Robert D.
Ross, George Webster
Launer, Lenore J.
White, Lon R.
TI Lifestyle and the Risk of Dementia in Japanese-American Men
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE dementia; lifestyle; risk
ID HONOLULU HEART PROGRAM; ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY; DIET;
DIAGNOSIS; ANCESTRY; CRITERIA; SMOKING; HAWAII
AB OBJECTIVES: To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia.
DESIGN: Case-control study nested in a prospective cohort.
SETTING: The Honolulu-Asia Aging Study, Oahu, Hawaii.
PARTICIPANTS: Three thousand four hundred sixty-eight Japanese-American men (mean age 52 in 1965-1968) examined for dementia 25 years later.
MEASUREMENTS: Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index (BMI) less than 25.0 kg/m(2), physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruits, vegetables, cereals, and ratio of monounsaturated to saturated fat). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for developing overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD), adjusting for potential confounders.
RESULTS: Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with greater risk of overall dementia (OR = 1.87, 95% CI = 1.26-2.77; BMI > 25.0 vs <22.6 kg/m(2)). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of the cohort) had the lowest OR for overall dementia (OR = 0.36, 95% CI = 0.15-0.84). There were no significant associations between the combined low-risk characteristics and the risk of AD alone.
CONCLUSION: Among Japanese-American men, having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life. J Am Geriatr Soc 60:118-123, 2012.
C1 [Gelber, Rebecca P.; Petrovitch, Helen; Masaki, Kamal H.; Abbott, Robert D.; Ross, George Webster; White, Lon R.] Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA.
[Gelber, Rebecca P.; Petrovitch, Helen; Ross, George Webster] Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI USA.
[Gelber, Rebecca P.] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA.
[Petrovitch, Helen; Masaki, Kamal H.; Ross, George Webster; White, Lon R.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA.
[Abbott, Robert D.] Univ Virginia, Sch Med, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Gelber, RP (reprint author), Kuakini Phys Tower,405 N Kuakini St,Ste 1111, Honolulu, HI 96817 USA.
EM rpgelber@gmail.com
FU National Institute on Aging [N01-AG-4-2149, 1-R01-AG17155-01A1];
National Heart, Lung, and Blood Institute [N01-HC-05102]; Office of
Research and Development, Medical Research Service, Department of
Veterans Affairs
FX Supported by Contract N01-AG-4-2149 and Grant 1-R01-AG17155-01A1 from
the National Institute on Aging; contract N01-HC-05102 from the National
Heart, Lung, and Blood Institute; and by the Office of Research and
Development, Medical Research Service, Department of Veterans Affairs.
The information contained in this article does not necessarily reflect
the position or the policy of the United States government, and no
official endorsement should be inferred.
NR 24
TC 18
Z9 18
U1 2
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2012
VL 60
IS 1
BP 118
EP 123
DI 10.1111/j.1532-5415.2011.03768.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 875PN
UT WOS:000299044100016
PM 22211390
ER
PT J
AU Grouls, S
Iglesias, DM
Wentzensen, N
Moeller, MJ
Bouchard, M
Kemler, R
Goodyer, P
Niggli, F
Grone, HJ
Kriz, W
Koesters, R
AF Grouls, Stephan
Iglesias, Diana Margarita
Wentzensen, Nicolas
Moeller, Marcus Johannes
Bouchard, Maxime
Kemler, Rolf
Goodyer, Paul
Niggli, Felix
Groene, Hermann-Josef
Kriz, Wilhelm
Koesters, Robert
TI Lineage Specification of Parietal Epithelial Cells Requires
beta-Catenin/Wnt Signaling
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID KIDNEY DEVELOPMENT; METANEPHRIC MESENCHYME; WNT; TRANSFORMATION;
EXPRESSION; GENE
AB beta-Catenin/Wnt signaling is essential during early inductive stages of kidney development, but its role during postinductive stages of nephron development and maturation is not well understood. In this study, we used Pax8Cre mice to target beta-catenin deficiency to renal epithelial cells at the late S-shaped body stage and the developing collecting ducts. The conditional beta-catenin knockout mice formed abnormal kidneys and had reduced renal function. The kidneys were hypoplastic with a thin cortex; a superficial layer of tubules was missing. A high proportion of glomeruli had small, underdeveloped capillary tufts. In these glomeruli, well differentiated podocytes replaced parietal epithelial cells in Bowman's capsule; capillaries toward the outer aspect of these podocytes mimicked the formation of glomerular capillaries. Tracing nephrogenesis in embryonic conditional beta-catenin knockout mice revealed that these "parietal podocytes" derived from precursor cells in the parietal layer of the S-shaped body by direct lineage switch. Taken together, these findings demonstrate that beta-catenin/Wnt signaling is important during the late stages of nephrogenesis and for the lineage specification of parietal epithelial cells.
C1 [Grouls, Stephan] Univ Heidelberg, Dept Nephrol, D-69120 Heidelberg, Baden Wurttembe, Germany.
[Grouls, Stephan] Univ Heidelberg, Inst Human Genet, D-69120 Heidelberg, Baden Wurttembe, Germany.
[Iglesias, Diana Margarita; Goodyer, Paul] McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Pediat,Hlth Ctr, Montreal, PQ H3H 1P3, Canada.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Moeller, Marcus Johannes] Rhein Westfael TH Aachen Univ, Univ Hosp, Dept Nephrol & Clin Immunol, Aachen, Germany.
[Bouchard, Maxime] McGill Univ, Dept Biochem, Goodman Canc Ctr, Montreal, PQ, Canada.
[Kemler, Rolf] Max Planck Inst Immunobiol, Dept Mol Embryol, Freiburg, Germany.
[Niggli, Felix] Univ Zurich, Childrens Hosp, Zurich, Switzerland.
[Groene, Hermann-Josef] Deutsch Krebsforschungszentrum, Div Cellular & Mol Pathol, D-6900 Heidelberg, Germany.
[Kriz, Wilhelm] Univ Heidelberg, Med Fac Mannheim, D-6800 Mannheim, Germany.
[Koesters, Robert] Univ Paris 06, Hosp Tenon, INSERM, Unit 702, Paris, France.
RP Grouls, S (reprint author), Univ Heidelberg, Dept Nephrol, Neuenheimer Feld 162, D-69120 Heidelberg, Baden Wurttembe, Germany.
EM stephan1.grouls@med.uni-heidelberg.de
RI Moeller, Marcus/L-1836-2015
FU Nikon Imaging Center at the University of Heidelberg
FX We thank Jeanette Weis, Hiltraud Hosser, Brunhilde Hahnel, Claudia
Schmidt, and Charlotte Holler for technical assistance and the Nikon
Imaging Center at the University of Heidelberg for their support. Ellen
Krautkramer contributed valuable critique.
NR 25
TC 29
Z9 30
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JAN
PY 2012
VL 23
IS 1
BP 63
EP 72
DI 10.1681/ASN.2010121257
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 877BK
UT WOS:000299151300012
PM 22021707
ER
PT J
AU Yu, BB
Zhou, C
AF Yu, Binbing
Zhou, Chuan
TI Assessing the accuracy of a multiphase diagnosis procedure for dementia
SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
LA English
DT Article
DE Dementia; Multiphase design; Receiver operating characteristic curve;
Screening; Verification bias
ID CHARACTERISTIC ROC CURVES; ALZHEIMERS-DISEASE; VERIFICATION BIAS; TESTS;
PREVALENCE; MARKERS; MODEL
AB . Multiphase (stage) designs that involve more than two phases are increasingly used by clinicians and psychologists for diagnosis and screening of dementia and many other diseases, e.g. colorectal or breast cancer. The multiphase design is an extension of the commonly used two-phase design, where an inexpensive initial screening test is followed by a gold standard. In a typical three-phase design, the screening test in phase 1 usually has high sensitivity but relatively low specificity. Phase 2 consists of a repeated application of the initial screening test and/or a more confirmatory test and then the gold standard test is used in phase 3. In such designs, both the verification process and the accuracy of each screening test may depend on patients characteristics. In addition, multiple-screening tests are correlated and composite decision rules may be used. However, no estimation methods exist for assessing the accuracy of a multiphase diagnosis procedure. To address these problems, we develop a method of estimating the diagnostic accuracy for each individual test and for the whole diagnostic procedure in a multiphase design in the presence of verification bias. Simulation studies are carried out to evaluate the performance of the method proposed and to compare different strategies of combining sequential tests. The method proposed is applied to data from a multiphase study of dementia.
C1 [Yu, Binbing] NIA, Bethesda, MD 20892 USA.
[Zhou, Chuan] Univ Washington, Seattle, WA 98195 USA.
[Zhou, Chuan] Childrens Hosp, Seattle, WA USA.
RP Yu, BB (reprint author), Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM yubi@mail.nih.gov
FU National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging. We thank Caroline Phillips for
editorial help.
NR 25
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0035-9254
EI 1467-9876
J9 J R STAT SOC C-APPL
JI J. R. Stat. Soc. Ser. C-Appl. Stat.
PY 2012
VL 61
BP 67
EP 81
DI 10.1111/j.1467-9876.2011.00771.x
PN 1
PG 15
WC Statistics & Probability
SC Mathematics
GA 877UH
UT WOS:000299207700004
ER
PT J
AU Dauer, LT
Thornton, RH
Miller, DL
Damilakis, J
Dixon, RG
Marx, V
Schueler, BA
Vano, E
Venkatesan, A
Bartal, G
Tsetis, D
Cardella, JF
AF Dauer, Lawrence T.
Thornton, Raymond H.
Miller, Donald L.
Damilakis, John
Dixon, Robert G.
Marx, Victoria
Schueler, Beth A.
Vano, Eliseo
Venkatesan, Aradhana
Bartal, Gabriel
Tsetis, Dimitrios
Cardella, John F.
CA Soc Interventional Radiology
Cardiovasc Interventional
TI Radiation Management for Interventions Using Fluoroscopic or Computed
Tomographic Guidance during Pregnancy: A Joint Guideline of the Society
of Interventional Radiology and the Cardiovascular and Interventional
Radiological Society of Europe with Endorsement by the Canadian
Interventional Radiology Association
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID EXPOSED IN-UTERO; CT PULMONARY ANGIOGRAPHY; SEVERE MENTAL-RETARDATION;
MONTE-CARLO SIMULATIONS; BOMB SURVIVORS; X-RAY; IONIZING-RADIATION;
CHILDHOOD-CANCER; MULTIDETECTOR CT; RADIOGRAPHIC EXAMINATIONS
C1 [Dauer, Lawrence T.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA.
[Thornton, Raymond H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, F Edward Hebert Sch Med, Bethesda, MD USA.
[Venkatesan, Aradhana] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Damilakis, John] Univ Crete, Dept Med Phys, Fac Med, Iraklion, Greece.
[Tsetis, Dimitrios] Univ Crete, Dept Radiol, Fac Med, Iraklion, Greece.
[Tsetis, Dimitrios] Univ Hosp Herakl, Dept Radiol, Iraklion, Greece.
[Dixon, Robert G.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
Los Angeles Cty, Dept Radiol, Los Angeles, CA USA.
Univ So Calif, Med Ctr, Los Angeles, CA USA.
[Schueler, Beth A.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Vano, Eliseo] Univ Complutense, Dept Radiol, E-28040 Madrid, Spain.
[Bartal, Gabriel] Meir Med Ctr, Dept Diagnost & Intervent Radiol, Kefar Sava, Israel.
[Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA.
RP Dauer, LT (reprint author), Care of Katsarelis D, SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA.
EM dauerl@mskcc.org
OI Dauer, Lawrence/0000-0002-5629-8462
NR 119
TC 21
Z9 22
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JAN
PY 2012
VL 23
IS 1
BP 19
EP 32
DI 10.1016/j.jvir.2011.09.007
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 877BL
UT WOS:000299151400004
PM 22112899
ER
PT J
AU Katki, HA
Wentzensen, N
AF Katki, Hormuzd A.
Wentzensen, Nicolas
TI How might HPV testing be integrated into cervical screening?
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID HUMAN-PAPILLOMAVIRUS; CANCER; CYTOLOGY; RISK
C1 [Katki, Hormuzd A.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM katkih@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015
FU Intramural NIH HHS [ZIA CP010217-01]
NR 11
TC 9
Z9 10
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JAN
PY 2012
VL 13
IS 1
BP 8
EP 10
DI 10.1016/S1470-2045(11)70334-5
PG 4
WC Oncology
SC Oncology
GA 875EZ
UT WOS:000299014500030
PM 22177578
ER
PT J
AU Schiffman, M
Wacholder, S
AF Schiffman, Mark
Wacholder, Sholom
TI Success of HPV vaccination is now a matter of coverage
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID HUMAN-PAPILLOMAVIRUS; EFFICACY; INFECTION; TRIAL
C1 [Schiffman, Mark; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM schiffmm@mail.nih.gov
FU Intramural NIH HHS
NR 10
TC 24
Z9 24
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JAN
PY 2012
VL 13
IS 1
BP 10
EP 12
DI 10.1016/S1470-2045(11)70324-2
PG 4
WC Oncology
SC Oncology
GA 875EZ
UT WOS:000299014500031
PM 22075169
ER
PT J
AU Garimella, SV
Rocca, A
Lipkowitz, S
AF Garimella, Sireesha V.
Rocca, Andrea
Lipkowitz, Stanley
TI WEE1 Inhibition Sensitizes Basal Breast Cancer Cells to TRAIL-Induced
Apoptosis
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; IN-VIVO; CHEMOTHERAPEUTIC DRUGS; IONIZING-RADIATION;
MEDIATED APOPTOSIS; ANTITUMOR EFFICACY; KINASE; LIGAND; THERAPY; DEATH
AB TRAIL is a member of the TNF super family and has been shown to induce apoptosis in many cancer cell lines but not in normal cells. Breast cancers can be divided into different subgroups on the basis of the expression of estrogen and progesterone receptors, HER-2 amplification, or the lack of these three markers (known as triple-negative or basal-type breast cancer). Our group and others have shown previously that triple-negative breast cancer cell lines are sensitive to TRAIL whereas others are relatively resistant. In an earlier study, we reported that inhibition of WEE1, a cell-cycle checkpoint regulator, causes increased cell death in breast cancer cell lines. In this study, we tested the effects of WEE1 inhibition on TRAIL-mediated apoptosis in breast cancer cell lines. Pretreatment with WEE1 inhibitor or knockdown of WEE1 increased the toxicity of TRAIL in the basal/triple-negative breast cancer cell lines compared with WEE1 inhibitor or TRAIL treatment alone. The enhanced cell death is attributed to increased surface expression of death receptors, increased caspase activation which could be blocked by the pan-caspase inhibitor, Z-VAD-FMK, thereby rescuing cells from caspase-mediated apoptosis. The cell death was initiated primarily by caspase-8 because knockdown of caspase-8 and not of any other initiator caspases (i.e., caspase-2, -9, or -10) rescued cells from WEE1 inhibitor-sensitized TRAIL-induced cell death. Taken together, the data suggest that the combination of WEE1 inhibitor and TRAIL could provide a novel combination for the treatment of basal/triple-negative breast cancer. Mol Cancer Res; 10(1); 75-85. (C) 2011 AACR.
C1 [Garimella, Sireesha V.; Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rocca, Andrea] Study & Treatment Canc IRST Ltd, Dept Med Oncol, Sci Inst Romagna, Meldola, FC, Italy.
RP Lipkowitz, S (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM lipkowis@mail.nih.gov
RI Rocca, Andrea/M-3930-2015
OI Rocca, Andrea/0000-0003-4613-8884
FU National Cancer Institute, Center for Cancer Research, NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, NIH.
NR 50
TC 11
Z9 12
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JAN
PY 2012
VL 10
IS 1
BP 75
EP 85
DI 10.1158/1541-7786.MCR-11-0500
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 879JJ
UT WOS:000299325200008
PM 22112940
ER
PT J
AU Vo, DT
Abdelmohsen, K
Martindale, JL
Qiao, M
Tominaga, K
Burton, TL
Gelfond, JAL
Brenner, AJ
Patel, V
Trageser, D
Scheffler, B
Gorospe, M
Penalva, LOF
AF Vo, Dat T.
Abdelmohsen, Kotb
Martindale, Jennifer L.
Qiao, Mei
Tominaga, Kumiko
Burton, Tarea L.
Gelfond, Jonathan A. L.
Brenner, Andrew J.
Patel, Vyomesh
Trageser, Daniel
Scheffler, Bjoern
Gorospe, Myriam
Penalva, Luiz O. F.
TI The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA
Translation and Stability in Glioblastoma Cells
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; POSTTRANSCRIPTIONAL GENE-REGULATION; NEURAL
STEM-CELLS; AU-RICH ELEMENTS; GLIOMA-CELLS; GENOMIC ANALYSES;
LUNG-CANCER; EXPRESSION; STABILIZATION; TARGET
AB Musashi1 (Msi1) is an evolutionarily conserved RNA-binding protein (RBP) that has profound implications in cellular processes such as stem cell maintenance, nervous system development, and tumorigenesis. Msi1 is highly expressed in many cancers, including glioblastoma, whereas in normal tissues, its expression is restricted to stem cells. Unfortunately, the factors that modulate Msi1 expression and trigger high levels in tumors are largely unknown. The Msi1 mRNA has a long 30 untranslated region (UTR) containing several AU- and U-rich sequences. This type of sequence motif is often targeted by HuR, another important RBP known to be highly expressed in tumor tissue such as glioblastoma and to regulate a variety of cancer-related genes. In this report, we show an interaction between HuR and the Msi1 3'-UTR, resulting in a positive regulation of Msi1 expression. We show that HuR increased MSI1 mRNA stability and promoted its translation. We also present evidence that expression of HuR and Msi1 correlate positively in clinical glioblastoma samples. Finally, we show that inhibition of cell proliferation, increased apoptosis, and changes in cell-cycle profile as a result of silencing HuR are partially rescued when Msi1 is ectopically expressed. In summary, our results suggest that HuR is an important regulator of Msi1 in glioblastoma and that this regulation has important biological consequences during gliomagenesis. Mol Cancer Res; 10(1); 143-55. (C) 2012 AACR.
C1 [Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Brenner, Andrew J.] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Med Oncol, Dept Med, San Antonio, TX 78229 USA.
[Brenner, Andrew J.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Abdelmohsen, Kotb; Martindale, Jennifer L.; Tominaga, Kumiko; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Patel, Vyomesh] Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Trageser, Daniel; Scheffler, Bjoern] Univ Bonn, Med Ctr, Inst Reconstruct Neurobiol, Bonn, Germany.
RP Penalva, LOF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Greehey Childrens Canc Res Inst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM penalva@uthscsa.edu
OI abdelmohsen, Kotb/0000-0001-6240-5810
FU National Institute on Aging, NIH; National Institute of Dental and
Craniofacial Research, NIH; Children's Brain Tumor Foundation;
Association for Research of Childhood Cancer; The Max and Minnie
Tomerlin Voelcker Fund; Cancer Therapy & Research Center P30 Cancer
Center from the National Cancer Institute [CA054174]
FX K. Abdelmohsen, J.L. Martindale, K. Tominaga, and M. Gorospe are
supported by the Intramural Research Program of the National Institute
on Aging, NIH. V. Patel is supported by the Intramural Research Program
at the National Institute of Dental and Craniofacial Research, NIH. D.T.
Vo, M. Qiao, T.L. Burton, and L.O.F. Penalva are supported by grants
from the Children's Brain Tumor Foundation, Association for Research of
Childhood Cancer, and The Max and Minnie Tomerlin Voelcker Fund. A. J.
Brenner is supported by the Cancer Therapy & Research Center P30 Cancer
Center Support Grant from the National Cancer Institute (CA054174).
NR 64
TC 24
Z9 24
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JAN
PY 2012
VL 10
IS 1
BP 143
EP 155
DI 10.1158/1541-7786.MCR-11-0208
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 879JJ
UT WOS:000299325200014
PM 22258704
ER
PT J
AU Kretschmannova, K
Kucka, M
Gonzalez-Iglesias, AE
Stojilkovic, SS
AF Kretschmannova, Karla
Kucka, Marek
Gonzalez-Iglesias, Arturo E.
Stojilkovic, Stanko S.
TI The Expression and Role of Hyperpolarization-Activated and Cyclic
Nucleotide-Gated Channels in Endocrine Anterior Pituitary Cells
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID BACKGROUND SODIUM CONDUCTANCE; HORMONE-RELEASING-HORMONE; NITRIC-OXIDE
SYNTHASE; CATION CHANNELS; CALCIUM INFLUX; HCN CHANNELS;
PROLACTIN-RELEASE; CA2+ OSCILLATIONS; GENE-EXPRESSION; ION CHANNELS
AB Pituitary cells fire action potentials independently of external stimuli, and such spontaneous electrical activity is modulated by a large variety of hypothalamic and intrapituitary agonists. Here, we focused on the potential role of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in electrical activity of cultured rat anterior pituitary cells. Quantitative RT-PCR analysis showed higher level of expression of mRNA transcripts for HCN2 and HCN3 subunits and lower expression of HCN1 and HCN4 subunits in these cells. Western immunoblot analysis of lysates from normal and GH(3) immortalized pituitary cells showed bands with appropriate molecular weights for HCN2, HCN3, and HCN4. Electrophysiological experiments showed the presence of a slowly developing hyperpolarization-activated inward current, which was blocked by Cs+ and ZD7288, in gonadotrophs, thyrotrophs, somatotrophs, and a fraction of lactotrophs, as well as in other unidentified pituitary cell types. Stimulation of adenylyl cyclase and addition of 8-Br-cAMP enhanced this current and depolarized the cell membrane, whereas 8-Br-cGMP did not alter the current and hyperpolarized the cell membrane. Both inhibition of basal adenylyl cyclase activity and stimulation of phospholipase C signaling pathway inhibited this current. Inhibition of HCN channels affected the frequency of firing but did not abolish spontaneous electrical activity. These experiments indicate that cAMP and cGMP have opposite effects on the excitability of endocrine pituitary cells, that basal cAMP production in cultured cells is sufficient to integrate the majority of HCN channels in electrical activity, and that depletion of phosphatidylinositol 4,5-bisphosphate caused by activation of phospholipase C silences them. (Molecular Endocrinology 26: 153-164, 2012)
C1 [Kretschmannova, Karla; Kucka, Marek; Gonzalez-Iglesias, Arturo E.; Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
FU NICHD, NIH
FX This work was supported by the Intramural Research Program of the NICHD,
NIH.
NR 58
TC 8
Z9 8
U1 0
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD JAN
PY 2012
VL 26
IS 1
BP 153
EP 164
DI 10.1210/me.2011-1207
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 877RO
UT WOS:000299199800014
PM 22135067
ER
PT J
AU Misteli, T
AF Misteli, Tom
TI Parallel genome universes
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
C1 NCI, US NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, US NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
NR 7
TC 4
Z9 4
U1 0
U2 2
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 JAN
PY 2012
VL 30
IS 1
BP 55
EP 56
DI 10.1038/nbt.2085
PG 2
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 876MC
UT WOS:000299110600018
PM 22231096
ER
PT J
AU Jiang, ML
Wang, JW
Fu, JR
Du, L
Jeong, H
West, T
Xiang, L
Peng, Q
Hou, ZP
Cai, H
Seredenina, T
Arbez, N
Zhu, SS
Sommers, K
Qian, J
Zhang, JY
Mori, S
Yang, XW
Tamashiro, KLK
Aja, S
Moran, TH
Luthi-Carter, R
Martin, B
Maudsley, S
Mattson, MP
Cichewicz, RH
Ross, CA
Holtzman, DM
Krainc, D
Duan, WZ
AF Jiang, Mali
Wang, Jiawei
Fu, Jinrong
Du, Lin
Jeong, Hyunkyung
West, Tim
Xiang, Lan
Peng, Qi
Hou, Zhipeng
Cai, Huan
Seredenina, Tamara
Arbez, Nicolas
Zhu, Shanshan
Sommers, Katherine
Qian, Jennifer
Zhang, Jiangyang
Mori, Susumu
Yang, X. William
Tamashiro, Kellie L. K.
Aja, Susan
Moran, Timothy H.
Luthi-Carter, Ruth
Martin, Bronwen
Maudsley, Stuart
Mattson, Mark P.
Cichewicz, Robert H.
Ross, Christopher A.
Holtzman, David M.
Krainc, Dimitri
Duan, Wenzhen
TI Neuroprotective role of Sirt1 in mammalian models of Huntington's
disease through activation of multiple Sirt1 targets
SO NATURE MEDICINE
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXO3A; TRANSGENIC MOUSE MODEL; NEUROTROPHIC
FACTOR; MUTANT HUNTINGTIN; IN-VITRO; NEURODEGENERATION; MICE;
PGC-1-ALPHA; METABOLISM; FORKHEAD
AB Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HIT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice)'. We now report that overexpression of sirtuin 1 (Sirt1), a mediator of the beneficial metabolic effects of calorie restriction, protects neurons against mutant HIT toxicity, whereas reduction of Sirt1 exacerbates mutant HIT toxicity. Overexpression of Sirt1 improves motor function, reduces brain atrophy and attenuates mutant-HTT-mediated metabolic abnormalities in Huntington's disease mice. Further mechanistic studies suggested that Sirt1 prevents the mutantHIT-induced decline in brain-derived neurotrophic factor (BDNF) concentrations and the signaling of its receptor, TrkB, and restores dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) concentrations in the striatum. Sirt1 deacetylase activity is required for Sirt1-mediated neuroprotection in Huntington's disease cell models. Notably, we show that mutant HIT interacts with Sirt1 and inhibits Sirti deacetylase activity, which results in hyperacetylation of Sirt1 substrates such as forkhead box O3A (Foxo3a), thereby inhibiting its pro-survival function. Overexpression of Sirt1 counteracts the mutant-HIT-induced deacetylase deficit, enhances the deacetylation of Foxo3a and facilitates cell survival. These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease.
C1 [Jiang, Mali; Wang, Jiawei; Fu, Jinrong; Xiang, Lan; Peng, Qi; Arbez, Nicolas; Zhu, Shanshan; Sommers, Katherine; Qian, Jennifer; Ross, Christopher A.; Duan, Wenzhen] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21205 USA.
[Wang, Jiawei] Capital Med Univ, Beijing Friendship Hosp, Beijing, Peoples R China.
[Du, Lin; Cichewicz, Robert H.] Univ Oklahoma, Dept Chem & Biochem, Nat Prod Discovery Grp, Norman, OK 73019 USA.
[Jeong, Hyunkyung; Krainc, Dimitri] Harvard Univ, Sch Med, Dept Neurol, MassGen Inst Neurodegenerat Dis,Massachusetts Gen, Boston, MA 02115 USA.
[West, Tim; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[West, Tim; Holtzman, David M.] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO USA.
[Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Cai, Huan; Martin, Bronwen] NIA, Metab Unit, Lab Clin Invest, US Natl Inst Hlth NIH, Baltimore, MD 21224 USA.
[Seredenina, Tamara; Luthi-Carter, Ruth] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland.
[Yang, X. William] Univ Calif Los Angeles, Brain Res Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
[Aja, Susan] Johns Hopkins Univ, Sch Med, Ctr Metab & Obes Res, Baltimore, MD USA.
[Maudsley, Stuart; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA.
[Ross, Christopher A.; Duan, Wenzhen] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD USA.
RP Duan, WZ (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21205 USA.
EM wduan2@jhmi.edu
RI Jiang, Mali/B-2631-2012; Du, Lin/G-7889-2011; Mattson, Mark/F-6038-2012;
Ross, Christopher/H-8395-2013; Cai, Huan/B-6578-2016;
OI Cai, Huan/0000-0001-7731-8891; Cichewicz, Robert/0000-0003-0744-4117
FU Hereditary Disease Foundation; CHDI Foundation [A-2120]; NIH [NS 16375,
NS35902, ROINS051303, EB003543, ES012665, NS065306]; NIA
FX We thank L. Tsai at Massachusetts Institute of Technology for providing
Sirt1 and H363Y retrovirus constructs, S. Imai at Washington University
for providing Sir2 complementary DNAs (cDNAs), M. Macdonald at Harvard
Medical School for providing STHdhQ7/Q7 and
STHdhQ111/Q111 cells, S. Li and X. Li at Emory University for
providing antibodies to EM48 and E. Waldron, C. Berlinicke, Y. Chen and
J. Jin at Johns Hopkins University School of Medicine for their
technical assistance. This work was supported by the Hereditary Disease
Foundation (W.D.), CHDI Foundation grant A-2120 (W.D.), NIH grant NS
16375 (C.A.R.), NIH grant NS35902 (D.M.H.), the NIA Intramural Research
Program (B.M., H.C., S. Maudesley and M.P.M.), NIH grant ROINS051303
(D.K.), NIH grant EB003543 and ES012665 (S. Mori) and NIH grant NS065306
(J.Z.).
NR 41
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U1 4
U2 31
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 JAN
PY 2012
VL 18
IS 1
BP 153
EP 158
DI 10.1038/nm.2558
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 875GO
UT WOS:000299018600042
ER
PT J
AU Resnick, SM
Scheltens, P
AF Resnick, Susan M.
Scheltens, Philip
TI MRI-based biomarkers of preclinical AD An Alzheimer signature
SO NEUROLOGY
LA English
DT Editorial Material
ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE;
COGNITIVE IMPAIRMENT; DISEASE; RECOMMENDATIONS
C1 [Resnick, Susan M.] NIA, Baltimore, MD 21224 USA.
[Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Alzheimer Ctr, Amsterdam, Netherlands.
RP Resnick, SM (reprint author), NIA, Baltimore, MD 21224 USA.
EM susan.resnick@nih.gov
FU Intramural NIH HHS [ZIA AG000191-15]
NR 7
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JAN
PY 2012
VL 78
IS 2
BP 80
EP 81
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 877EL
UT WOS:000299159700005
PM 22189450
ER
PT J
AU Heremans, E
Nieuwboer, A
Feys, P
Vercruysse, S
Vandenberghe, W
Sharma, N
Helsen, WF
AF Heremans, Elke
Nieuwboer, Alice
Feys, Peter
Vercruysse, Sarah
Vandenberghe, Wim
Sharma, Nikhil
Helsen, Werner F.
TI External Cueing Improves Motor Imagery Quality in Patients With
Parkinson Disease
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE mental practice; motor imagery; cueing; Parkinson disease;
rehabilitation
ID MENTAL MOVEMENT TIMES; HAND MOVEMENTS; MULTIPLE-SCLEROSIS; INTENTION
TREMOR; VISUAL FEEDBACK; BASAL GANGLIA; ARM MOVEMENTS; GRAPHIC TASKS;
STROKE; GAIT
AB Background. Patients with Parkinson disease (PD) are often profoundly slow in their performance of physical tasks, as well as in motor imagery (MI). This may limit the implementation and potential benefits of MI practice during rehabilitation. Objective. The authors investigated whether the quality of MI could be improved by external cueing. Methods. Fourteen patients with PD and 14 healthy controls physically executed and visually imagined a goal-directed aiming task and a box-and-block task, both in the presence and absence of visual and auditory cues. Mental chronometry and eye movement recording allowed objective evaluation of the temporal and spatial characteristics of MI when compared with physical execution. Visual analogue scales were used to assess imagery vividness. Results. The presence of visual cues significantly reduced the patients' bradykinesia during MI and increased their imagery vividness. Conclusions. Visual cueing optimizes MI quality for PD patients and is a potential tool to increase the efficacy of MI practice in PD rehabilitation.
C1 [Helsen, Werner F.] Katholieke Univ Leuven, Dept Biomed Kinesiol, Percept & Performance Lab, B-3001 Louvain, Belgium.
[Feys, Peter] PHL Univ Coll, Hasselt, Belgium.
[Feys, Peter] Univ Hasselt, Hasselt, Belgium.
[Vandenberghe, Wim] Univ Hosp Leuven, Louvain, Belgium.
[Sharma, Nikhil] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Helsen, WF (reprint author), Katholieke Univ Leuven, Dept Biomed Kinesiol, Percept & Performance Lab, Tervuursevest 101, B-3001 Louvain, Belgium.
EM werner.helsen@faber.kuleuven.be
RI Nieuwboer, Alice/F-5643-2013;
OI Nieuwboer, Alice/0000-0003-1193-6229; Sharma, Nikhil/0000-0001-8903-2938
FU Belgian Charcot Foundation
FX Elke Heremans is a research assistant and Wim Vandenberghe a senior
clinical investigator at the Research Foundation Flanders (FWO). The
authors also acknowledge the support of the Belgian Charcot Foundation
to obtain eye movement recording equipment.
NR 61
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U1 1
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD JAN
PY 2012
VL 26
IS 1
BP 27
EP 35
DI 10.1177/1545968311411055
PG 9
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 876BQ
UT WOS:000299082400004
PM 21778409
ER
PT J
AU Lai, JS
Nowinski, C
Victorson, D
Bode, R
Podrabsky, T
McKinney, N
Straube, D
Holmes, GL
McDonald, CM
Henricson, E
Abresch, RT
Moy, CS
Cella, D
AF Lai, Jin-Shei
Nowinski, Cindy
Victorson, David
Bode, Rita
Podrabsky, Tracy
McKinney, Natalie
Straube, Don
Holmes, Gregory L.
McDonald, Craig M.
Henricson, Erik
Abresch, R. Ted
Moy, Claudia S.
Cella, David
TI Quality-of-Life Measures in Children With Neurological Conditions:
Pediatric Neuro-QOL
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE health-related quality of life; children; neurological disorders; item
bank; item response theory
ID PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; OUTCOMES; VALIDATION; EPILEPSY;
STROKE; SCALE; REHABILITATION; INSTRUMENT; DISABILITY
AB Background. A comprehensive, reliable, and valid measurement system is needed to monitor changes in children with neurological conditions who experience lifelong functional limitations. Objective. This article describes the development and psychometric properties of the pediatric version of the Quality of Life in Neurological Disorders (Neuro-QOL) measurement system. Methods. The pediatric Neuro-QOL consists of generic and targeted measures. Literature review, focus groups, individual interviews, cognitive interviews of children and consensus meetings were used to identify and finalize relevant domains and item content. Testing was conducted on 1018 children aged 10 to 17 years drawn from the US general population for generic measures and 171 similarly aged children with muscular dystrophy or epilepsy for targeted measures. Dimensionality was evaluated using factor analytic methods. For unidimensional domains, item parameters were estimated using item response theory models. Measures with acceptable fit indices were calibrated as item banks; those without acceptable fit indices were treated as summary scales. Results. Ten measures were developed: 8 generic or targeted banks (anxiety, depression, anger, interaction with peers, fatigue, pain, applied cognition, and stigma) and 2 generic scales (upper and lower extremity function). The banks reliably (r > 0.90) measured 63.2% to 100% of the children tested. Conclusions. The pediatric Neuro-QOL is a comprehensive measurement system with acceptable psychometric properties that could be used in computerized adaptive testing. The next step is to validate these measures in various clinical populations.
C1 [Lai, Jin-Shei] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Straube, Don] Univ Illinois, Chicago, IL USA.
[Holmes, Gregory L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[McDonald, Craig M.; Henricson, Erik; Abresch, R. Ted] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
[Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Lai, JS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 710 N Lake Shore Dr,724, Chicago, IL 60611 USA.
EM js-lai@northwestern.edu
OI McDonald, Craig/0000-0002-8779-3220
FU National Institute of Neurological Disorders and Stroke
[HHSN265200423601C]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
project is supported by the National Institute of Neurological Disorders
and Stroke (HHSN265200423601C; Principal Investigator: David Cella).
NR 36
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U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD JAN
PY 2012
VL 26
IS 1
BP 36
EP 47
DI 10.1177/1545968311412054
PG 12
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 876BQ
UT WOS:000299082400001
PM 21788436
ER
PT J
AU Ndongwe, TP
Adedeji, AO
Michailidis, E
Ong, YT
Hachiya, A
Marchand, B
Ryan, EM
Rai, DK
Kirby, KA
Whatley, AS
Burke, DH
Johnson, M
Ding, SL
Zheng, YM
Liu, SL
Kodama, EI
Delviks-Frankenberry, KA
Pathak, VK
Mitsuya, H
Parniak, MA
Singh, K
Sarafianos, SG
AF Ndongwe, Tanyaradzwa P.
Adedeji, Adeyemi O.
Michailidis, Eleftherios
Ong, Yee Tsuey
Hachiya, Atsuko
Marchand, Bruno
Ryan, Emily M.
Rai, Devendra K.
Kirby, Karen A.
Whatley, Angela S.
Burke, Donald H.
Johnson, Marc
Ding, Shilei
Zheng, Yi-Min
Liu, Shan-Lu
Kodama, Ei-Ichi
Delviks-Frankenberry, Krista A.
Pathak, Vinay K.
Mitsuya, Hiroaki
Parniak, Michael A.
Singh, Kamalendra
Sarafianos, Stefan G.
TI Biochemical, inhibition and inhibitor resistance studies of xenotropic
murine leukemia virus-related virus reverse transcriptase
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CHRONIC-FATIGUE-SYNDROME; HUMAN RETROVIRUS XMRV; CRYSTAL-STRUCTURE;
DRUG-RESISTANCE; DNA-SYNTHESIS; PROSTATE-CANCER; IN-VITRO; INFECTIOUS
RETROVIRUS; POLYMERASE FIDELITY; ANGSTROM RESOLUTION
AB We report key mechanistic differences between the reverse transcriptases (RT) of human immunodeficiency virus type-1 (HIV-1) and of xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus that can infect human cells. Steady and pre-steady state kinetics demonstrated that XMRV RT is significantly less efficient in DNA synthesis and in unblocking chain-terminated primers. Surface plasmon resonance experiments showed that the gammaretroviral enzyme has a remarkably higher dissociation rate (k(off)) from DNA, which also results in lower processivity than HIV-1 RT. Transient kinetics of mismatch incorporation revealed that XMRV RT has higher fidelity than HIV-1 RT. We identified RNA aptamers that potently inhibit XMRV, but not HIV-1 RT. XMRV RT is highly susceptible to some nucleoside RT inhibitors, including Translocation Deficient RT inhibitors, but not to non-nucleoside RT inhibitors. We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1.
C1 [Ndongwe, Tanyaradzwa P.; Adedeji, Adeyemi O.; Michailidis, Eleftherios; Ong, Yee Tsuey; Hachiya, Atsuko; Marchand, Bruno; Ryan, Emily M.; Rai, Devendra K.; Kirby, Karen A.; Whatley, Angela S.; Burke, Donald H.; Johnson, Marc; Zheng, Yi-Min; Liu, Shan-Lu; Singh, Kamalendra; Sarafianos, Stefan G.] Univ Missouri, Christopher Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Sch Med, Columbia, MO 65211 USA.
[Burke, Donald H.; Sarafianos, Stefan G.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA.
[Ding, Shilei; Liu, Shan-Lu] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada.
[Kodama, Ei-Ichi] Tohoku Univ, Sch Med, Dept Internal Med, Div Emerging Infect Dis, Sendai, Miyagi 980, Japan.
[Delviks-Frankenberry, Krista A.; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Internal Med, Kumamoto 860, Japan.
[Mitsuya, Hiroaki] NIH, Expt Retrovirol Sect, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Parniak, Michael A.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA.
RP Sarafianos, SG (reprint author), Univ Missouri, Christopher Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Sch Med, Columbia, MO 65211 USA.
EM sarafianoss@missouri.edu
RI Kodama, Eiichi /C-4032-2009; Rai, Devendra/J-3857-2013;
Delviks-Frankenberry, Krista/M-4822-2013; Liu, Shan-Lu/L-5923-2016;
OI Kirby, Karen A./0000-0003-2468-4796; Kodama, Eiichi
/0000-0002-6622-2752; Rai, Devendra/0000-0001-9035-685X; Liu,
Shan-Lu/0000-0003-1620-3817; Sarafianos, Stefan G/0000-0002-5840-154X
FU NIH [AI076119, AI079801, AI094715, AI074389]; NIH, National Cancer
Institute, Center for Cancer Research; Ministry of Knowledge and
Economy, Republic of Korea; Canadian Institutes of Health Research
(CIHR); University of Missouri
FX NIH grants (AI076119, AI079801, and AI094715, to S. G. S.), (AI074389,
to D. H. B.), (AI079801 to M. A. P.); NIH Bench-to-Bedside Award and the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (to V. K. P); Ministry of Knowledge and
Economy, Bilateral International Collaborative R&D Program, Republic of
Korea; Canadian Institutes of Health Research (CIHR) and University of
Missouri (to S-L. L.); amfAR Mathilde Krim Fellowship and a CIHR
Fellowship (to B. M.). Funding for open access charge: NIH grants
(AI076119, AI094715, AI074389, AI079801).
NR 84
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U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS 1
BP 345
EP 359
DI 10.1093/nar/gkr694
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 871JG
UT WOS:000298733500038
PM 21908397
ER
PT J
AU Asagoshi, K
Lehmann, W
Braithwaite, EK
Santana-Santos, L
Prasad, R
Freedman, JH
Van Houten, B
Wilson, SH
AF Asagoshi, Kenjiro
Lehmann, Wade
Braithwaite, Elena K.
Santana-Santos, Lucas
Prasad, Rajendra
Freedman, Jonathan H.
Van Houten, Bennett
Wilson, Samuel H.
TI Single-nucleotide base excision repair DNA polymerase activity in C.
elegans in the absence of DNA polymerase beta
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID NEMATODE CAENORHABDITIS-ELEGANS; X-FAMILY; IDENTIFICATION; HOMOLOG;
GENES; SITE; PURIFICATION; GLYCOSYLASE; RESISTANCE; LONGEVITY
AB The base excision DNA repair (BER) pathway known to occur in Caenorhabditis elegans has not been well characterized. Even less is known about the DNA polymerase (pol) requirement for the gap-filling step during BER. We now report on characterization of in vitro uracil-DNA initiated BER in C. elegans. The results revealed single-nucleotide (SN) gap-filling DNA polymerase activity and complete BER. The gap-filling polymerase activity was not due to a DNA polymerase beta (pol beta) homolog, or to another X-family polymerase, since computer-based sequence analyses of the C. elegans genome failed to show a match for a pol beta-like gene or other X-family polymerases. Activity gel analysis confirmed the absence of pol beta in the C. elegans extract. BER gap-filling polymerase activity was partially inhibited by both dideoxy-nucleotide and aphidicolin. The results are consistent with a combination of both replicative polymerase(s) and lesion bypass/BER polymerase pol theta contributing to the BER gap-filling synthesis. Involvement of pol theta was confirmed in experiments with extract from pol theta null animals. The presence of the SN BER in C. elegans is supported by these results, despite the absence of a pol beta-like enzyme or other X-family polymerase.
C1 [Asagoshi, Kenjiro; Prasad, Rajendra; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Lehmann, Wade; Van Houten, Bennett] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Braithwaite, Elena K.; Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Santana-Santos, Lucas; Van Houten, Bennett] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15213 USA.
[Santana-Santos, Lucas; Van Houten, Bennett] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
OI Santana-Santos, Lucas/0000-0002-0872-5431
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES050158, Z01ES050159]; U.S. Government; NIH
National Center for Research Resources; [Z01-ES061060]; [Z01ES102045];
[R01-ES019566]
FX The Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences (grants Z01ES050158
and Z01ES050159 to S. H. W., partial); Z01-ES061060 and Z01ES102045 to
J.H.F., partial); (R01-ES019566 to B. V. H., partial). Funding for open
access charge: U.S. Government funds.; We thank Bonnie Mesmer for
editorial assistance, Julie A. Hall, Julie R. Rice, Kathryn L. Haas and
Windy A. Boyd for their assistance with nematode genotyping and
culturing and anonymous reviewers for suggestions. Nematodes strains
used in this work were provided by the Caenorhabditis Genetics Center,
which is funded by the NIH National Center for Research Resources.
NR 51
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U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS 2
BP 670
EP 681
DI 10.1093/nar/gkr727
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 876GP
UT WOS:000299095900024
PM 21917855
ER
PT J
AU Callahan, KE
Hickman, AB
Jones, CE
Ghirlando, R
Furano, AV
AF Callahan, Kathryn E.
Hickman, Alison B.
Jones, Charles E.
Ghirlando, Rodolfo
Furano, Anthony V.
TI Polymerization and nucleic acid-binding properties of human L1 ORF1
protein
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RIBONUCLEOPROTEIN PARTICLE FORMATION; PRIMED REVERSE TRANSCRIPTION;
LINE-1 RETROTRANSPOSITION; CHAPERONE ACTIVITY; MOUSE LINE-1;
RNA-BINDING; HUMAN GENOMES; IN-VITRO; EVOLUTION; ELEMENT
AB The L1 (LINE 1) retrotransposable element encodes two proteins, ORF1p and ORF2p. ORF2p is the L1 replicase, but the role of ORF1p is unknown. Mouse ORF1p, a coiled-coil-mediated trimer of similar to 42-kDa monomers, binds nucleic acids and has nucleic acid chaperone activity. We purified human L1 ORF1p expressed in insect cells and made two findings that significantly advance our knowledge of the protein. First, in the absence of nucleic acids, the protein polymerizes under the very conditions (0.05M NaCl) that are optimal for high (similar to 1 nM)-affinity nucleic acid binding. The non-coiled-coil C-terminal half mediates formation of the polymer, an active conformer that is instantly resolved to trimers, or multimers thereof, by nucleic acid. Second, the protein has a biphasic effect on mismatched double-stranded DNA, a proxy chaperone substrate. It protects the duplex from dissociation at 37 degrees C before eventually melting it when largely polymeric. Therefore, polymerization of ORF1p seemingly affects its interaction with nucleic acids. Additionally, polymerization of ORF1p at its translation site could explain the heretofore-inexplicable phenomenon of cis preference-the favored retrotransposition of the actively translated L1 transcript, which is essential for L1 survival.
C1 [Callahan, Kathryn E.; Jones, Charles E.; Furano, Anthony V.] NIDDK, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
[Callahan, Kathryn E.] Georgetown Univ, Dept Biochem & Mol & Cell Biol, Med Ctr, Washington, DC 20057 USA.
[Hickman, Alison B.; Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Furano, AV (reprint author), NIDDK, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
EM avf@helix.nih.gov
FU NIDDK/NIH
FX The Intramural Program of the National Institute of Diabetes, Digestive
and Kidney Diseases (NIDDK)/National Institutes of Health (NIH). Funding
for open access charge: NIDDK/NIH.
NR 50
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U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS 2
BP 813
EP 827
DI 10.1093/nar/gkr728
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 876GP
UT WOS:000299095900036
PM 21937507
ER
PT J
AU Barrett, T
Clark, K
Gevorgyan, R
Gorelenkov, V
Gribov, E
Karsch-Mizrachi, I
Kimelman, M
Pruitt, KD
Resenchuk, S
Tatusova, T
Yaschenko, E
Ostell, J
AF Barrett, Tanya
Clark, Karen
Gevorgyan, Robert
Gorelenkov, Vyacheslav
Gribov, Eugene
Karsch-Mizrachi, Ilene
Kimelman, Michael
Pruitt, Kim D.
Resenchuk, Sergei
Tatusova, Tatiana
Yaschenko, Eugene
Ostell, James
TI BioProject and BioSample databases at NCBI: facilitating capture and
organization of metadata
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENOMICS; SYSTEM
AB As the volume and complexity of data sets archived at NCBI grow rapidly, so does the need to gather and organize the associated metadata. Although metadata has been collected for some archival databases, previously, there was no centralized approach at NCBI for collecting this information and using it across databases. The BioProject database was recently established to facilitate organization and classification of project data submitted to NCBI, EBI and DDBJ databases. It captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. Concomitantly, the BioSample database is being developed to capture descriptive information about the biological samples investigated in projects. BioProject and BioSample records link to corresponding data stored in archival repositories. Submissions are supported by a web-based Submission Portal that guides users through a series of forms for input of rich metadata describing their projects and samples. Together, these databases offer improved ways for users to query, locate, integrate and interpret the masses of data held in NCBI's archival repositories. The BioProject and BioSample databases are available at http://www.ncbi.nlm.nih.gov/biosample, respectively.
C1 [Barrett, Tanya; Clark, Karen; Gevorgyan, Robert; Gorelenkov, Vyacheslav; Gribov, Eugene; Karsch-Mizrachi, Ilene; Kimelman, Michael; Pruitt, Kim D.; Resenchuk, Sergei; Tatusova, Tatiana; Yaschenko, Eugene; Ostell, James] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Karsch-Mizrachi, I (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA.
EM mizrachi@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for Open Access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 17
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U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D57
EP D63
DI 10.1093/nar/gkr1163
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300010
PM 22139929
ER
PT J
AU Benson, DA
Karsch-Mizrachi, I
Clark, K
Lipman, DJ
Ostell, J
Sayers, EW
AF Benson, Dennis A.
Karsch-Mizrachi, Ilene
Clark, Karen
Lipman, David J.
Ostell, James
Sayers, Eric W.
TI GenBank
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENERATION; DATABASE
AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 250 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI home page: www.ncbi.nlm.nih.gov.
C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Clark, Karen; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 11
TC 264
Z9 268
U1 1
U2 24
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D48
EP D53
DI 10.1093/nar/gkr1202
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300008
PM 22144687
ER
PT J
AU Federhen, S
AF Federhen, Scott
TI The NCBI Taxonomy database
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB The NCBI Taxonomy database (http://www.ncbi.nlm.nih.gov/taxonomy)is the standard nomenclature and classification repository for the International Nucleotide Sequence Database Collaboration (INSDC), comprising the GenBank, ENA (EMBL) and DDBJ databases. It includes organism names and taxonomic lineages for each of the sequences represented in the INSDC's nucleotide and protein sequence databases. The taxonomy database is manually curated by a small group of scientists at the NCBI who use the current taxonomic literature to maintain a phylogenetic taxonomy for the source organisms represented in the sequence databases. The taxonomy database is a central organizing hub for many of the resources at the NCBI, and provides a means for clustering elements within other domains of NCBI web site, for internal linking between domains of the Entrez system and for linking out to taxon-specific external resources on the web. Our primary purpose is to index the domain of sequences as conveniently as possible for our user community.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Federhen, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM federhen@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine; Intramural
Research Program
FX Intramural Research Program of the National Institutes of Health,
National Library of Medicine. Funding for open access charge: Intramural
Research Program.
NR 16
TC 156
Z9 158
U1 2
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D136
EP D143
DI 10.1093/nar/gkr1178
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300021
PM 22139910
ER
PT J
AU Galperin, MY
Fernandez-Suarez, XM
AF Galperin, Michael Y.
Fernandez-Suarez, Xose M.
TI The 2012 Nucleic Acids Research Database Issue and the online Molecular
Biology Database Collection
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB The 19th annual Database Issue of Nucleic Acids Research features descriptions of 92 new online databases covering various areas of molecular biology and 100 papers describing recent updates to the databases previously described in NAR and other journals. The highlights of this issue include, among others, a description of neXtProt, a knowledgebase on human proteins; a detailed explanation of the principles behind the NCBI Taxonomy Database; NCBI and EBI papers on the recently launched BioSample databases that store sample information for a variety of database resources; descriptions of the recent developments in the Gene Ontology and UniProt Gene Ontology Annotation projects; updates on Pfam, SMART and InterPro domain databases; update papers on KEGG and TAIR, two universally acclaimed databases that face an uncertain future; and a separate section with 10 wiki-based databases, introduced in an accompanying editorial. The NAR online Molecular Biology Database Collection, available at http://www.oxfordjournals.org/nar/database/a/, has been updated and now lists 1380 databases. Brief machine-readable descriptions of the databases featured in this issue, according to the BioDBcore standards, will be provided at the http://biosharing.org/biodbcore web site. The full content of the Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).
C1 [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat NCBI, Natl Lib Med, Bethesda, MD 20894 USA.
[Fernandez-Suarez, Xose M.] Wellcome Trust Genome Campus, EMBL European Bioinformat Inst, Cambridge CB10 1SD, England.
RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat NCBI, Natl Lib Med, Bethesda, MD 20894 USA.
EM galperin@ncbi.nlm.nih.gov; xose@ebi.ac.uk
RI Galperin, Michael/B-5859-2013
OI Galperin, Michael/0000-0002-2265-5572
FU US National Institutes of Health at the National Library of Medicine;
European Molecular Biology Laboratory; Oxford University Press
FX Intramural Research Program of the US National Institutes of Health at
the National Library of Medicine (to M.Y.G.); European Molecular Biology
Laboratory (to X. M. F. S.). Funding for open access charge: waived by
Oxford University Press.
NR 44
TC 45
Z9 45
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D1
EP D8
DI 10.1093/nar/gkr1196
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300001
PM 22144685
ER
PT J
AU Karsch-Mizrachi, I
Nakamura, Y
Cochrane, G
AF Karsch-Mizrachi, Ilene
Nakamura, Yasukazu
Cochrane, Guy
CA Int Nucleotide Sequence Database C
TI The International Nucleotide Sequence Database Collaboration
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB The members of the International Nucleotide Sequence Database Collaboration (INSDC; http://www.insdc.org) set out to capture, preserve and present globally comprehensive public domain nucleotide sequence information. The work of the long-standing collaboration includes the provision of data formats, annotation conventions and routine global data exchange. Among the many developments to INSDC resources in 2011 are the newly launched BioProject database and improved handling of assembly information. In this article, we outline INSDC services and update the reader on developments in 2011.
C1 [Karsch-Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Nakamura, Yasukazu] Res Org Informat & Syst, Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 4118510, Japan.
[Nakamura, Yasukazu] Res Org Informat & Syst, Natl Inst Genet, DNA Data Bank Japan, Mishima, Shizuoka 4118510, Japan.
[Cochrane, Guy] Wellcome Trust Genome Campus, EMBL European Bioinformat Inst, Cambridge CB10 1SD, England.
RP Karsch-Mizrachi, I (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA.
EM mizrachi@ncbi.nlm.nih.gov
RI Salzberg, Steven/F-6162-2011;
OI Salzberg, Steven/0000-0002-8859-7432; Cochrane, Guy/0000-0001-7954-7057;
Nakamura, Yasukazu/0000-0002-6782-5715; Danchin,
Antoine/0000-0002-6350-5001
FU National Institutes of Health; National Library of Medicine; European
Nucleotide Archive by the European Molecular Biology Laboratory;
Wellcome Trust; European Commission; Biotechnology and Biological
Sciences Research Council; Ministry of Education, Culture, Sports,
Science and Technology of Japan; National Institutes of Health, National
Library of Medicine
FX NCBI by the Intramural Research Program of the National Institutes of
Health; National Library of Medicine; European Nucleotide Archive by the
European Molecular Biology Laboratory, the Wellcome Trust, the FP7
Programme of the European Commission and the Biotechnology and
Biological Sciences Research Council; at DDBJ by the Ministry of
Education, Culture, Sports, Science and Technology of Japan. Funding for
open access charge: the Intramural Research Program of the National
Institutes of Health, National Library of Medicine.
NR 5
TC 44
Z9 45
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D33
EP D37
DI 10.1093/nar/gkr1006
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300005
PM 22080546
ER
PT J
AU Kodama, Y
Shumway, M
Leinonen, R
AF Kodama, Yuichi
Shumway, Martin
Leinonen, Rasko
CA Int Nucleotide Sequence Database C
TI The sequence read archive: explosive growth of sequencing data
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB New generation sequencing platforms are producing data with significantly higher throughput and lower cost. A portion of this capacity is devoted to individual and community scientific projects. As these projects reach publication, raw sequencing datasets are submitted into the primary next-generation sequence data archive, the Sequence Read Archive (SRA). Archiving experimental data is the key to the progress of reproducible science. The SRA was established as a public repository for next-generation sequence data as a part of the International Nucleotide Sequence Database Collaboration (INSDC). INSDC is composed of the National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EBI) and the DNA Data Bank of Japan (DDBJ). The SRA is accessible at www.ebi.ac.uk/ena from EBI and at trace.ddbj.nig.ac.jp from DDBJ. In this article, we present the content and structure of the SRA and report on updated metadata structures, submission file formats and supported sequencing platforms. We also briefly outline our various responses to the challenge of explosive data growth.
C1 [Kodama, Yuichi] Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan.
[Kodama, Yuichi] Res Org Informat & Syst, DNA Data Bank Japan, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
[Shumway, Martin] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Leinonen, Rasko] Wellcome Trust Genome Campus, European Bioinformat Inst, Cambridge CB10 1SD, England.
RP Kodama, Y (reprint author), Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan.
EM ykodama@genes.nig.ac.jp
OI Cochrane, Guy/0000-0001-7954-7057; Leinonen, Rasko/0000-0002-2639-7187
FU DNA Data Bank of Japan; Ministry of Education, Culture, Sports, Science
and Technology of Japan; European Molecular Biology Laboratory; European
Commission; Wellcome Trust; National Library of Medicine; NIH
FX DNA Data Bank of Japan, Ministry of Education, Culture, Sports, Science
and Technology of Japan; European Molecular Biology Laboratory, European
Commission and the Wellcome Trust; National Library of Medicine;
Intramural Research Program of the NIH. Funding for open access charge:
Ministry of Education, Culture, Sports, Science and Technology of Japan
(management expense grant).
NR 8
TC 171
Z9 175
U1 4
U2 23
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D54
EP D56
DI 10.1093/nar/gkr854
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300009
PM 22009675
ER
PT J
AU Li, MLJ
Wang, PW
Liu, XR
Lim, EL
Wang, ZY
Yeager, M
Wong, MP
Sham, PC
Chanock, SJ
Wang, JW
AF Li, Mulin Jun
Wang, Panwen
Liu, Xiaorong
Lim, Ee Lyn
Wang, Zhangyong
Yeager, Meredith
Wong, Maria P.
Sham, Pak Chung
Chanock, Stephen J.
Wang, Junwen
TI GWASdb: a database for human genetic variants identified by genome-wide
association studies
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID OPEN-ACCESS DATABASE; TRANSCRIPTION FACTOR; WEB DATABASE; SNP;
ANNOTATION; PHENOTYPE; SELECTION; DISEASE; PROFILES; GENOTYPE
AB Recent advances in genome-wide association studies (GWAS) have enabled us to identify thousands of genetic variants (GVs) that are associated with human diseases. As next-generation sequencing technologies become less expensive, more GVs will be discovered in the near future. Existing databases, such as NHGRI GWAS Catalog, collect GVs with only genome-wide level significance. However, many true disease susceptibility loci have relatively moderate P values and are not included in these databases. We have developed GWASdb that contains 20 times more data than the GWAS Catalog and includes less significant GVs (P < 1.0 x 10(-3)) manually curated from the literature. In addition, GWASdb provides comprehensive functional annotations for each GV, including genomic mapping information, regulatory effects (transcription factor binding sites, microRNA target sites and splicing sites), amino acid substitutions, evolution, gene expression and disease associations. Furthermore, GWASdb classifies these GVs according to diseases using Disease-Ontology Lite and Human Phenotype Ontology. It can conduct pathway enrichment and PPI network association analysis for these diseases. GWASdb provides an intuitive, multifunctional database for biologists and clinicians to explore GVs and their functional inferences. It is freely available at http://jjwanglab.org/gwasdb and will be updated frequently.
C1 [Li, Mulin Jun; Wang, Panwen; Liu, Xiaorong; Lim, Ee Lyn; Wang, Zhangyong; Wang, Junwen] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Lim, Ee Lyn] Univ Oxford, Trinity Coll, Oxford, England.
[Wang, Zhangyong] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA.
[Yeager, Meredith] SAIC Frederick Inc, Core Genotyping Facil, Frederick, MD USA.
[Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wong, Maria P.] Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
RP Wang, JW (reprint author), Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
EM junwen@uw.edu
RI Wang, Junwen/C-4432-2009; Wang, Junwen/D-3700-2011
OI Wang, Junwen/0000-0002-4432-4707
FU University of Hong Kong [201007176262]; Research Grants Council of Hong
Kong [781511M, 778609M, N_HKU752/10]; Food and Health Bureau of Hong
Kong [10091262]; National Cancer Institute (NCI), NIH, USA
FX The Small Project Fund (201007176262) of the University of Hong Kong;
Research Grants Council of Hong Kong (781511M, 778609M, N_HKU752/10);
Food and Health Bureau of Hong Kong (10091262); The intramural research
program of the National Cancer Institute (NCI), NIH, USA. Funding for
open access charge: Research Grants Council (781511M) of Hong Kong.
NR 43
TC 68
Z9 72
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D1047
EP D1054
DI 10.1093/nar/gkr1182
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300157
PM 22139925
ER
PT J
AU Madej, T
Addess, KJ
Fong, JH
Geer, LY
Geer, RC
Lanczycki, CJ
Liu, CL
Lu, SN
Marchler-Bauer, A
Panchenko, AR
Chen, J
Thiessen, PA
Wang, YL
Zhang, DC
Bryant, SH
AF Madej, Thomas
Addess, Kenneth J.
Fong, Jessica H.
Geer, Lewis Y.
Geer, Renata C.
Lanczycki, Christopher J.
Liu, Chunlei
Lu, Shennan
Marchler-Bauer, Aron
Panchenko, Anna R.
Chen, Jie
Thiessen, Paul A.
Wang, Yanli
Zhang, Dachuan
Bryant, Stephen H.
TI MMDB: 3D structures and macromolecular interactions
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN; DATABASE
AB Close to 60% of protein sequences tracked in comprehensive databases can be mapped to a known three-dimensional (3D) structure by standard sequence similarity searches. Potentially, a great deal can be learned about proteins or protein families of interest from considering 3D structure, and to this day 3D structure data may remain an underutilized resource. Here we present enhancements in the Molecular Modeling Database (MMDB) and its data presentation, specifically pertaining to biologically relevant complexes and molecular interactions. MMDB is tightly integrated with NCBI's Entrez search and retrieval system, and mirrors the contents of the Protein Data Bank. It links protein 3D structure data with sequence data, sequence classification resources and PubChem, a repository of small-molecule chemical structures and their biological activities, facilitating access to 3D structure data not only for structural biologists, but also for molecular biologists and chemists. MMDB provides a complete set of detailed and pre-computed structural alignments obtained with the VAST algorithm, and provides visualization tools for 3D structure and structure/sequence alignment via the molecular graphics viewer Cn3D. MMDB can be accessed at http://www.ncbi.nlm.nih.gov/structure.
C1 [Madej, Thomas; Addess, Kenneth J.; Fong, Jessica H.; Geer, Lewis Y.; Geer, Renata C.; Lanczycki, Christopher J.; Liu, Chunlei; Lu, Shennan; Marchler-Bauer, Aron; Panchenko, Anna R.; Chen, Jie; Thiessen, Paul A.; Wang, Yanli; Zhang, Dachuan; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Madej, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM madej@ncbi.nlm.nih.gov
RI Geer, Lewis/H-2714-2014;
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU National Library of Medicine at National Institutes of Health/DHHS
FX Funding to pay the open access charge: Intramural Research Program of
the National Library of Medicine at National Institutes of Health/DHHS.
Comments, suggestions and questions are welcome and should be directed
to: info@ncbi.nlm.nih.gov.
NR 9
TC 53
Z9 55
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D461
EP D464
DI 10.1093/nar/gkr1162
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300067
PM 22135289
ER
PT J
AU Pruitt, KD
Tatusova, T
Brown, GR
Maglott, DR
AF Pruitt, Kim D.
Tatusova, Tatiana
Brown, Garth R.
Maglott, Donna R.
TI NCBI Reference Sequences (RefSeq): current status, new features and
genome annotation policy
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RESOURCES; DATABASE
AB The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of genomic, transcript and protein sequence records. These records are selected and curated from public sequence archives and represent a significant reduction in redundancy compared to the volume of data archived by the International Nucleotide Sequence Database Collaboration. The database includes over 16 000 organisms, 2.4 x 10(6) genomic records, 13 x 10(6) proteins and 2 x 10(6) RNA records spanning prokaryotes, eukaryotes and viruses (RefSeq release 49, September 2011). The RefSeq database is maintained by a combined approach of automated analyses, collaboration and manual curation to generate an up-to-date representation of the sequence, its features, names and cross-links to related sources of information. We report here on recent growth, the status of curating the human RefSeq data set, more extensive feature annotation and current policy for eukaryotic genome annotation via the NCBI annotation pipeline. More information about the resource is available online (see http://www.ncbi.nlm.nih.gov/RefSeq/).
C1 [Pruitt, Kim D.; Tatusova, Tatiana; Brown, Garth R.; Maglott, Donna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM pruitt@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 14
TC 516
Z9 524
U1 1
U2 42
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D130
EP D135
DI 10.1093/nar/gkr1079
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300020
PM 22121212
ER
PT J
AU Sayers, EW
Barrett, T
Benson, DA
Bolton, E
Bryant, SH
Canese, K
Chetvernin, V
Church, DM
DiCuccio, M
Federhen, S
Feolo, M
Fingerman, IM
Geer, LY
Helmberg, W
Kapustin, Y
Krasnov, S
Landsman, D
Lipman, DJ
Lu, ZY
Madden, TL
Madej, T
Maglott, DR
Marchler-Bauer, A
Miller, V
Karsch-Mizrachi, I
Ostell, J
Panchenko, A
Phan, L
Pruitt, KD
Schuler, GD
Sequeira, E
Sherry, ST
Shumway, M
Sirotkin, K
Slotta, D
Souvorov, A
Starchenko, G
Tatusova, TA
Wagner, L
Wang, YL
Wilbur, WJ
Yaschenko, E
Ye, J
AF Sayers, Eric W.
Barrett, Tanya
Benson, Dennis A.
Bolton, Evan
Bryant, Stephen H.
Canese, Kathi
Chetvernin, Vyacheslav
Church, Deanna M.
DiCuccio, Michael
Federhen, Scott
Feolo, Michael
Fingerman, Ian M.
Geer, Lewis Y.
Helmberg, Wolfgang
Kapustin, Yuri
Krasnov, Sergey
Landsman, David
Lipman, David J.
Lu, Zhiyong
Madden, Thomas L.
Madej, Tom
Maglott, Donna R.
Marchler-Bauer, Aron
Miller, Vadim
Karsch-Mizrachi, Ilene
Ostell, James
Panchenko, Anna
Phan, Lon
Pruitt, Kim D.
Schuler, Gregory D.
Sequeira, Edwin
Sherry, Stephen T.
Shumway, Martin
Sirotkin, Karl
Slotta, Douglas
Souvorov, Alexandre
Starchenko, Grigory
Tatusova, Tatiana A.
Wagner, Lukas
Wang, Yanli
Wilbur, W. John
Yaschenko, Eugene
Ye, Jian
TI Database resources of the National Center for Biotechnology Information
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ONLINE MENDELIAN INHERITANCE; BIOLOGICAL PATHWAYS; PROTEIN SEQUENCES;
GENOMES; SEARCH; ENTREZ; NCBI; SYSTEM; GENES; KEGG
AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Website. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe, Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
C1 [Sayers, Eric W.; Barrett, Tanya; Benson, Dennis A.; Bolton, Evan; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Federhen, Scott; Feolo, Michael; Fingerman, Ian M.; Geer, Lewis Y.; Kapustin, Yuri; Krasnov, Sergey; Landsman, David; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madej, Tom; Maglott, Donna R.; Marchler-Bauer, Aron; Miller, Vadim; Karsch-Mizrachi, Ilene; Ostell, James; Panchenko, Anna; Phan, Lon; Pruitt, Kim D.; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Slotta, Douglas; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A.; Wagner, Lukas; Wang, Yanli; Wilbur, W. John; Yaschenko, Eugene; Ye, Jian] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Helmberg, Wolfgang] Med Univ Graz, Univ Clin Blood Grp Serol & Transfus Med, A-8036 Graz, Austria.
RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
RI Geer, Lewis/H-2714-2014;
OI Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman,
David/0000-0002-9819-6675
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 60
TC 304
Z9 311
U1 2
U2 50
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D13
EP D25
DI 10.1093/nar/gkr1184
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300003
PM 22140104
ER
PT J
AU Shoemaker, BA
Zhang, DC
Tyagi, M
Thangudu, RR
Fong, JH
Marchler-Bauer, A
Bryant, SH
Madej, T
Panchenko, AR
AF Shoemaker, Benjamin A.
Zhang, Dachuan
Tyagi, Manoj
Thangudu, Ratna R.
Fong, Jessica H.
Marchler-Bauer, Aron
Bryant, Stephen H.
Madej, Thomas
Panchenko, Anna R.
TI IBIS (Inferred Biomolecular Interaction Server) reports, predicts and
integrates multiple types of conserved interactions for proteins
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID LIGAND-BINDING-SITES; WEB SERVER; ANNOTATION; SEQUENCES; PARTNERS;
DATABASE
AB We have recently developed the Inferred Biomolecular Interaction Server (IBIS) and database, which reports, predicts and integrates different types of interaction partners and locations of binding sites in proteins based on the analysis of homologous structural complexes. Here, we highlight several new IBIS features and options. The server's webpage is now redesigned to allow users easier access to data for different interaction types. An entry page is added to give a quick summary of available results and to now accept protein sequence accessions. To elucidate the formation of protein complexes, not just binary interactions, IBIS currently presents an expandable interaction network. Previously, IBIS provided annotations for four different types of binding partners: proteins, small molecules, nucleic acids and peptides; in the current version a new protein-ion interaction type has been added. Several options provide easy downloads of IBIS data for all Protein Data Bank (PDB) protein chains and the results for each query. In this study, we show that about one-third of all RefSeq sequences can be annotated with IBIS interaction partners and binding sites. The IBIS server is available at http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.cgi and updated biweekly.
C1 [Shoemaker, Benjamin A.; Zhang, Dachuan; Tyagi, Manoj; Thangudu, Ratna R.; Fong, Jessica H.; Marchler-Bauer, Aron; Bryant, Stephen H.; Madej, Thomas; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA.
EM madej@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov
RI Tyagi, Manoj/K-8438-2014;
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU National Institutes of Health/Department of Health and Human Service
(DHHS); National Library of Medicine; National Institutes of Health
FX National Institutes of Health/Department of Health and Human Service
(DHHS) (Intramural Research program of the National Library of
Medicine). Funding for open access charge: National Institutes of Health
Intramural Program.
NR 25
TC 32
Z9 32
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D834
EP D840
DI 10.1093/nar/gkr997
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300125
PM 22102591
ER
PT J
AU Wang, YL
Xiao, JW
Suzek, TO
Zhang, J
Wang, JY
Zhou, ZG
Han, LY
Karapetyan, K
Dracheva, S
Shoemaker, BA
Bolton, E
Gindulyte, A
Bryant, SH
AF Wang, Yanli
Xiao, Jewen
Suzek, Tugba O.
Zhang, Jian
Wang, Jiyao
Zhou, Zhigang
Han, Lianyi
Karapetyan, Karen
Dracheva, Svetlana
Shoemaker, Benjamin A.
Bolton, Evan
Gindulyte, Asta
Bryant, Stephen H.
TI PubChem's BioAssay Database
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CHEMICAL BIOLOGY; CIRCADIAN CLOCK
AB PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological activity data of small molecules and RNAi reagents. The mission of PubChem is to deliver free and easy access to all deposited data, and to provide intuitive data analysis tools. The PubChem BioAssay database currently contains 500 000 descriptions of assay protocols, covering 5000 protein targets, 30 000 gene targets and providing over 130 million bioactivity outcomes. PubChem's bioassay data are integrated into the NCBI Entrez information retrieval system, thus making PubChem data searchable and accessible by Entrez queries. Also, as a repository, PubChem constantly optimizes and develops its deposition system answering many demands of both high- and low-volume depositors. The PubChem information platform allows users to search, review and download bioassay description and data. The PubChem platform also enables researchers to collect, compare and analyze biological test results through web-based and programmatic tools. In this work, we provide an update for the PubChem BioAssay resource, including information content growth, data model extension and new developments of data submission, retrieval, analysis and download tools.
C1 [Wang, Yanli; Xiao, Jewen; Suzek, Tugba O.; Zhang, Jian; Wang, Jiyao; Zhou, Zhigang; Han, Lianyi; Karapetyan, Karen; Dracheva, Svetlana; Shoemaker, Benjamin A.; Bolton, Evan; Gindulyte, Asta; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Suzek, Tugba/B-6943-2015;
OI Suzek, Tugba/0000-0002-3243-1759
FU NIH; US government
FX The NIH Intramural Research program. Funding for open access charge: US
government.
NR 13
TC 195
Z9 199
U1 2
U2 28
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2012
VL 40
IS D1
BP D400
EP D412
DI 10.1093/nar/gkr1132
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 869MD
UT WOS:000298601300059
PM 22140110
ER
PT J
AU Hostetler, JA
Onorato, DP
Bolker, BM
Johnson, WE
O'Brien, SJ
Jansen, D
Oli, MK
AF Hostetler, Jeffrey A.
Onorato, David P.
Bolker, Benjamin M.
Johnson, Warren E.
O'Brien, Stephen J.
Jansen, Deborah
Oli, Madan K.
TI Does genetic introgression improve female reproductive performance? A
test on the endangered Florida panther
SO OECOLOGIA
LA English
DT Article
DE Abundance; Cumulative logit regression; Demography; Model-averaging;
Season
ID ET-AL. 2006; INBREEDING DEPRESSION; CARNIVORE MANAGEMENT; COUGAR
DEMOGRAPHY; HUNTED POPULATION; DYNAMICS; METAPOPULATION; RESTORATION;
ADVANTAGE; CONCOLOR
AB Genetic introgression has been suggested as a management tool for mitigating detrimental effects of inbreeding depression, but the role of introgression in species conservation has been controversial, partly because population-level impacts of genetic introgressions are not well understood. Concerns about potential inbreeding depression in the endangered Florida panther (Puma concolor coryi) led to the release of eight female Texas pumas (P. c. stanleyana) into the Florida panther population in 1995. We used long-term reproductive data (1995-2008) collected from 61 female Florida panthers to estimate and model reproduction probability (probability of producing a litter) and litter size, and to investigate the influence of intentional genetic introgression on these parameters. Overall, 6-month probability of reproduction (+/- 1SE) was 0.232 +/- 0.021 and average litter size was 2.60 +/- 0.09. Although F(1) admixed females had a lower reproduction probability than females with other ancestries, this was most likely because kittens born to F(1) females survive better; consequently, these females are unavailable for breeding until kittens are independent. There was no evidence for the effect of ancestry on litter size or of heterozygosity on probability of reproduction or litter size. In contrast, earlier studies have shown that genetic introgression positively affected Florida panther survival. Our results, along with those of earlier studies, clearly suggest that genetic introgression can have differential effects on components of fitness and highlight the importance of examining multiple demographic parameters when evaluating the effects of management actions.
C1 [Hostetler, Jeffrey A.; Oli, Madan K.] Univ Florida, Dept Wildlife Ecol & Conservat, Gainesville, FL 32611 USA.
[Onorato, David P.] Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, Naples, FL 34114 USA.
[Bolker, Benjamin M.] McMaster Univ, Dept Math & Stat, Hamilton, ON L86 4K1, Canada.
[Bolker, Benjamin M.] McMaster Univ, Dept Biol, Hamilton, ON L86 4K1, Canada.
[Johnson, Warren E.; O'Brien, Stephen J.] Natl Canc Inst, Lab Genom Div, Frederick, MD 21702 USA.
[Jansen, Deborah] Big Cypress Natl Preserve, Ochopee, FL 34141 USA.
RP Hostetler, JA (reprint author), Natl Zool Pk, Migratory Bird Ctr, Smithsonian Conservat Biol Inst, Washington, DC 20013 USA.
EM hostetlerj@si.edu
RI Hostetler, Jeffrey/A-3345-2011; Johnson, Warren/D-4149-2016;
OI Hostetler, Jeffrey/0000-0003-3669-1758; Johnson,
Warren/0000-0002-5954-186X; Bolker, Benjamin/0000-0002-2127-0443
FU Florida Panther Research and Management Trust, National Park Service,
University of Florida, United States Fish and Wildlife Service
[401816G091]
FX We thank D. Land, M. Cunningham, Roy McBride, M. Lotz, D. Shindle, M.
Criffield, S. Schulze, D. Giardina, A. Johnson, L. Oberhofer, M.
Alvarado, H. Fitting, T. O'Meara, and Rocky, Rowdy, and C. McBride and
others for assistance with fieldwork. We also thank J. Nichols for
statistical advice, M. Roelke for genetic analyses, and J. Nichols, M.
Sunquist, and two anonymous reviewers for reviewing an earlier draft of
this manuscript. This work was funded through the Florida Panther
Research and Management Trust Fund, National Park Service, University of
Florida, and grant Agreement No: 401816G091 from the United States Fish
and Wildlife Service. The views and conclusions presented herein are
those of the authors and do not necessarily reflect the views and
conclusions of the federal government.
NR 58
TC 6
Z9 6
U1 2
U2 76
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0029-8549
J9 OECOLOGIA
JI Oecologia
PD JAN
PY 2012
VL 168
IS 1
BP 289
EP 300
DI 10.1007/s00442-011-2083-0
PG 12
WC Ecology
SC Environmental Sciences & Ecology
GA 875TN
UT WOS:000299058100027
PM 21805300
ER
PT J
AU Bruno, RD
Boulanger, CA
Smith, GH
AF Bruno, R. D.
Boulanger, C. A.
Smith, G. H.
TI Notch-induced mammary tumorigenesis does not involve the lobule-limited
epithelial progenitor
SO ONCOGENE
LA English
DT Article
DE lobular progenitor; PI-MEC; Int3; Notch4; mammary development
ID GLAND DEVELOPMENT; TUMOR VIRUS; PROGESTERONE-RECEPTOR; STEM-CELLS;
IN-VIVO; EXPRESSION; DIFFERENTIATION; RENEWAL; INT-3; GENE
AB The mouse mammary epithelial cell hierarchy contains both multipotent stem cell as well as lineage-limited duct and lobular progenitor cell functions. The latter-also termed parity-identified mammary epithelial cells (PI-MECs)-are marked by beta-galactosidase (beta Gal) expression following pregnancy and involution in whey acidic protein promoter (WAP)-Cre/Rosa26-flox-stop-flox-lacZ (WC/R26) mice, and are the targets of tumorigenic transformation in mouse mammary tumor virus-erbB2 transgenic mice. In this study, we demonstrate that an epithelial population distinct from PI-MECs is transformed during WAP-Int3 tumorigenesis. As expected, WAP-Int3/WC/R26 triple-transgenic mice failed to undergo secretory alveolar development, failed to lactate and developed mammary tumors. Following pregnancy and involution, beta Gal+ mammary epithelial cells were found in the normal mammary tissue, but the resulting mammary tumors were all beta Gal-. WAP-Int3/WC/R26 mammary glands contained ample estrogen receptor alpha (ER alpha)+ MECs, but only rare (<1%) progesterone receptor (PR)+ and RANKL+ cells. In addition, dissociated MECs from WAP-Int3/WC/R26 glands failed to regenerate a mammary tree upon transplantation into a cleared fat-pad of a nu/nu recipient mouse. However, when mixed with normal MECs, PI-MECs from WAP-Int3/WC/R26 mice contributed progeny to the resulting functional outgrowth. The WAP-Int3/WC/R26-derived PI-MECs displayed all of the properties of fully functional lobular progenitors including giving rise to ER alpha+, PR+, smooth muscle actin+ and RANKL+ epithelial progeny. These results demonstrate that WAP-Int3 has no oncogenic effect upon PI-MECs and that the expansion of functional lobular progenitors is required for secretory alveolar development and lactation. Furthermore, lobular progenitor function is ultimately controlled by signals within its microenvironment. Oncogene (2012) 31, 60-67; doi: 10.1038/onc.2011.215; published online 13 June 2011
C1 [Smith, G. H.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 1112B, Bethesda, MD 20892 USA.
EM smithg@mail.nih.gov
OI Bruno, Robert/0000-0003-3329-9478
FU NCI's Center for Cancer Research
FX The NCI's Center for Cancer Research Intramural Research Program funded
this work.
NR 23
TC 7
Z9 7
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2012
VL 31
IS 1
BP 60
EP 67
DI 10.1038/onc.2011.215
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 877JT
UT WOS:000299176200006
PM 21666720
ER
PT J
AU Lee, MH
Lahusen, T
Wang, RH
Xiao, C
Xu, X
Hwang, YS
He, WW
Shi, Y
Deng, CX
AF Lee, M-H
Lahusen, T.
Wang, R-H
Xiao, C.
Xu, X.
Hwang, Y-S
He, W-W
Shi, Y.
Deng, C-X
TI Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer
formation
SO ONCOGENE
LA English
DT Article
DE BRCA1; breast cancer; promoter; nude mice; YY1
ID SPORADIC BREAST-CANCER; TUMOR-SUPPRESSOR; ADENOVIRUS E1A;
TRANSCRIPTIONAL REPRESSION; GENE-EXPRESSION; FACTOR YY1; C-MYC;
PROMOTER; BINDING; YIN-YANG-1
AB Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer. Oncogene (2012) 31, 116-127; doi: 10.1038/onc.2011.217; published online 13 June 2011
C1 [Lee, M-H; Lahusen, T.; Wang, R-H; Xiao, C.; Xu, X.; Deng, C-X] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hwang, Y-S] NCI, Lab Cell & Dev Signaling, NIH, Frederick, MD 21701 USA.
[He, W-W] Origene Technol Inc, Rockville, MD USA.
[Shi, Y.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 9N105, Bethesda, MD 20892 USA.
EM chuxiad@bdg10.niddk.nih.gov
RI deng, chuxia/N-6713-2016
FU National Institute of Diabetes, Digestive and Kidney Diseases, National
Institutes of Health, USA
FX We thank members of Dr Deng laboratory for their critical discussion of
this work and technical assistance. This research was supported by the
Intramural Research Program of the National Institute of Diabetes,
Digestive and Kidney Diseases, National Institutes of Health, USA.
NR 54
TC 16
Z9 17
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2012
VL 31
IS 1
BP 116
EP 127
DI 10.1038/onc.2011.217
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 877JT
UT WOS:000299176200011
PM 21666725
ER
PT J
AU Pla, AF
Ong, HL
Cheng, KT
Brossa, A
Bussolati, B
Lockwich, T
Paria, B
Munaron, L
Ambudkar, IS
AF Pla, A. Fiorio
Ong, H. L.
Cheng, K. T.
Brossa, A.
Bussolati, B.
Lockwich, T.
Paria, B.
Munaron, L.
Ambudkar, I. S.
TI TRPV4 mediates tumor-derived endothelial cell migration via arachidonic
acid-activated actin remodeling
SO ONCOGENE
LA English
DT Article
DE Ca2+ signals; TRP channels; endothelial cells; cell migration; actin
remodeling; tumor angiogenesis
ID PROTEIN-KINASE; ION CHANNELS; CA2+ ENTRY; PLASMA-MEMBRANE; IN-VIVO;
ANGIOGENESIS; EXPRESSION; GROWTH; PROLIFERATION; TRANSLOCATION
AB Changes in intracellular calcium [Ca2+](i) levels control critical cytosolic and nuclear events that are involved in the initiation and progression of tumor angiogenesis in endothelial cells (ECs). Therefore, the mechanism(s) involved in agonist-induced Ca-i(2+) signaling is a potentially important molecular target for controlling angiogenesis and tumor growth. Several studies have shown that blood vessels in tumors differ from normal vessels in their morphology, blood flow and permeability. We had previously reported a key role for arachidonic acid (AA)-mediated Ca2+ entry in the initial stages of tumor angiogenesis in vitro. In this study we assessed the mechanism involved in AA-induced EC migration. We report that TRPV4, an AA-activated channel, is differentially expressed in EC derived from human breast carcinomas (BTEC) as compared with 'normal' EC (HMVEC). BTEC display a significant increase in TRPV4 expression, which was correlated with greater Ca2+ entry, induced by AA or 4 alpha PDD (a selective TRPV4 agonist) in the tumor-derived ECs. Wound-healing assays revealed a key role of TRPV4 in regulating cell migration of BTEC but not HMVEC. Knockdown of TRPV4 expression completely abolished AA-induced BTEC migration, suggesting that TRPV4 mediates the pro-angiogenic effects promoted by AA. Furthermore, pre-incubation of BTEC with AA induced actin remodeling and a subsequent increase in the surface expression of TRPV4. This was consistent with the increased plasma membrane localization of TRPV4 and higher AA-stimulated Ca2+ entry in the migrating cells. Together, the data presented herein demonstrate that: (1) TRPV4 is differentially expressed in tumor-derived versus 'normal' EC; (2) TRPV4 has a critical role in the migration of tumor-derived but not 'normal' EC migration; and (3) AA induces actin remodeling in BTEC, resulting in a corresponding increase of TRPV4 expression in the plasma membrane. We suggest that the latter is critical for migration of EC and thus in promoting angiogenesis and tumor growth. Oncogene (2012) 31, 200-212; doi:10.1038/onc.2011.231; published online 20 June 2011
C1 [Pla, A. Fiorio; Brossa, A.; Munaron, L.] Univ Turin, Dept Anim & Human Biol, I-10123 Turin, Italy.
[Pla, A. Fiorio; Munaron, L.] Ctr Complex Syst Mol Biol & Med SysBioM, Turin, Italy.
[Pla, A. Fiorio; Munaron, L.] Nanostruct Interfaces & Surfaces Ctr Excellence, Turin, Italy.
[Ong, H. L.; Cheng, K. T.; Lockwich, T.; Paria, B.; Ambudkar, I. S.] NIDCR, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Brossa, A.; Bussolati, B.] Univ Turin, Ctr Mol Biotechnol, Dept Internal Med, Turin, Italy.
RP Pla, AF (reprint author), Univ Turin, Dept Anim & Human Biol, V Accademia Albertina 13, I-10123 Turin, Italy.
EM alessandra.fiorio@unito.it
RI Fiorio Pla, Alessandra/B-6646-2012;
OI Fiorio Pla, Alessandra/0000-0003-4576-1594; Bussolati,
Benedetta/0000-0002-3663-5134
FU University of Torino; Regione Piemonte (Ricerca Scientifica Applicata
Sanita'); National Institute of Dental and Craniofacial Research
FX This work was supported by the University of Torino, Regione Piemonte
(Ricerca Scientifica Applicata Sanita') and the National Institute of
Dental and Craniofacial Research (Intramural Research). We thank Dr
Kenneth Yamada (NIDCR, NIH, Bethesda, MD, USA) for the
beta-actin-mCherry and Dr Michael X. Zhu (Department of Physiology and
Cell Biology, Ohio State University, OH, USA) for the TRPV4-GFP
construct.
NR 53
TC 27
Z9 27
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2012
VL 31
IS 2
BP 200
EP 212
DI 10.1038/onc.2011.231
PG 13
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 879CN
UT WOS:000299307400006
ER
PT J
AU Roescher, N
Lodde, BM
Vosters, JL
Tak, PP
Catalan, MA
Illei, GG
Chiorini, JA
AF Roescher, N.
Lodde, B. M.
Vosters, J. L.
Tak, P. P.
Catalan, M. A.
Illei, G. G.
Chiorini, J. A.
TI Temporal changes in salivary glands of non-obese diabetic mice as a
model for Sjogren's syndrome
SO ORAL DISEASES
LA English
DT Article
DE Sjogren's syndrome; salivary gland; autoimmune sialadenitis; non-obese
diabetic mouse; immunology
ID INTERCELLULAR-ADHESION MOLECULE-1; NOD MOUSE MODEL; LYMPHOCYTIC
INFILTRATION; LYMPHOID ORGANIZATION; RITUXIMAB TREATMENT;
AUTOIMMUNE-DISEASE; CIRCULATING LEVELS; EPITHELIAL-CELLS; DENDRITIC
CELLS; HIGH EXPRESSION
AB OBJECTIVE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy that shows similarities with Sjogren's syndrome. They provide an experimental model to study the pathoetiogenesis of this disease.
MATERIALS AND METHODS: Salivary gland (SG) function and salivary sodium content were measured in 8-, 12-, 16- and 20-week-old NOD and age-matched CB6 mice. In NOD mice, SG expression of phenotypic cell markers, B cell-stimulating and costimulatory molecules were evaluated. Cytokine levels were measured in serum and SG homogenates.
RESULTS: Microscopically evident SG inflammation in NOD mice was preceded by expression of intercellular adhesion molecule 1 on epithelial cells in the presence of macrophages and relatively high levels of cytokines. Next, an influx consisting of mainly T, B, natural killer, plasma and dendritic cells was seen. Most cytokines, except for interleukin (IL) 12/IL23p40 and B cell-activating factor, decreased or remained stable over time, while glandular function deteriorated from 16 weeks of age onward compared with CB6 mice.
CONCLUSION: Sjogren's syndrome-like disease in NOD mice occurs in multiple stages; immunological and physiological abnormalities can be detected before focal inflammation appears and salivary output declines. Extrapolating this knowledge to human subjects could help in understanding the pathogenesis and aid the identification of potential therapeutic targets.
C1 [Roescher, N.; Lodde, B. M.; Vosters, J. L.; Tak, P. P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1100 DE Amsterdam, Netherlands.
[Roescher, N.; Vosters, J. L.; Illei, G. G.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Catalan, M. A.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD USA.
RP Roescher, N (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, POB 22700, NL-1100 DE Amsterdam, Netherlands.
EM n.roescher@amc.uva.nl
OI Catalan, Marcelo/0000-0003-3544-2821
FU NIH; Dutch Arthritis Association; NIH Fellows Editorial Board for
editorial assistance
FX The authors declare no conflict of interest. This research was funded by
an Intramural NIH grant to JAC and a grant from the Dutch Arthritis
Association to JLV. We thank the NIH Fellows Editorial Board for
editorial assistance, Corine van der Horst for technical assistance with
the digital image analysis and Dr J. E. Melvin for assistance with the
sodium measurements.
NR 54
TC 13
Z9 13
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD JAN
PY 2012
VL 18
IS 1
BP 96
EP 106
DI 10.1111/j.1601-0825.2011.01852.x
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 869JD
UT WOS:000298593300011
PM 21914088
ER
PT J
AU Shankaran, S
Laptook, AR
McDonald, SA
Higgins, RD
Tyson, JE
Ehrenkranz, RA
Das, A
Sant'Anna, G
Goldberg, RN
Bara, R
Walsh, MC
AF Shankaran, Seetha
Laptook, Abbot R.
McDonald, Scott A.
Higgins, Rosemary D.
Tyson, Jon E.
Ehrenkranz, Richard A.
Das, Abhik
Sant'Anna, Guilherme
Goldberg, Ronald N.
Bara, Rebecca
Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst
TI Temperature profile and outcomes of neonates undergoing whole body
hypothermia for neonatal hypoxic-ischemic encephalopathy
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE encephalopathy; hypothermia; hypoxia-ischemia; newborn; temperature;
whole-body cooling
ID MODERATE HYPOTHERMIA; TRIAL
AB Background: Decreases below the target temperature were noted among neonates undergoing cooling in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy.
Objective: To examine the temperature profile and impact on outcome among >= 36 wk gestation neonates randomized at <= 6 hrs of age targeting an esophageal temperature of 33.5 degrees C for 72 hrs.
Design, Setting, Patients: Infants with intermittent temperatures recorded of <32.0 degrees C during induction and maintenance of cooling were compared to all other cooled infants, and the relationship with outcome at 18 months was evaluated.
Interventions: None.
Measurements and Main Results: There were no differences in the stage of encephalopathy, acidosis, or 10 min Apgar scores between infants with temperatures of <32.0 degrees C during induction (n = 33) or maintenance (n = 10) and all other infants who were cooled (n = 58); however, birth weight was lower and the need for blood pressure support higher among infants with temperatures of <32.0 degrees C compared to all other cooled infants. No increase in acute adverse events was noted among infants with temperatures of <32.0 degrees C, and hours spent at <32 degrees C was not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months.
Conclusions: Term infants with a lower birth weight are at risk for decreasing temperatures of <32.0 degrees C while undergoing body cooling using a servo-controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy. (Pediatr Crit Care Med 2012; 13:53-59)
C1 [Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[McDonald, Scott A.; Das, Abhik] RTI Int, Res Triangle Pk, NC USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Tyson, Jon E.] Univ Texas Houston, Houston, TX USA.
[Ehrenkranz, Richard A.] Yale Univ, New Haven, CT USA.
[Sant'Anna, Guilherme] McGill Univ, Montreal, PQ, Canada.
[Goldberg, Ronald N.] Duke Univ, Durham, NC USA.
[Walsh, Michele C.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Shankaran, S (reprint author), Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
EM sshankar@med.wayne.edu
FU Case Western University, Cleveland, OH [U10 HD21364]; University of
Texas at Houston, TX [U10 HD21373]; Wayne State University, Detroit, MI
[U10 HD21385]; University of Miami, FL [U10 HD21397]; Emory University,
Atlanta, GA [U10 HD27851]; University of Cincinnati, OH [U10 HD27853];
Indiana University, Bloomington, IN [U10 HD27856]; Yale University, New
Haven, CT [U10 HD27871]; Stanford University, Stanford, CA [U10
HD27880]; Brown University, Providence, RI [U10 HD27904]; University of
Alabama, Birmingham, AL [U10 HD34216]; RTI International, Research
Triangle Park, NC [U10 HD36790]; University of California-San Diego, CA
[U10 HD40461]; Duke University, Durham, NC [U10 HD40492]; Wake Forest
University, Winston-Salem, NC [U10 HD40498]
FX Supported, in part, by grants U10 HD21364 (Case Western University,
Cleveland, OH), U10 HD21373 (University of Texas at Houston, TX), U10
HD21385 (Wayne State University, Detroit, MI), U10 HD21397 (University
of Miami, FL), U10 HD27851 (Emory University, Atlanta, GA), U10 HD27853
(University of Cincinnati, OH), U10 HD27856 (Indiana University,
Bloomington, IN), U10 HD27871 (Yale University, New Haven, CT), U10
HD27880 (Stanford University, Stanford, CA), U10 HD27904 (Brown
University, Providence, RI), U10 HD34216 (University of Alabama,
Birmingham, AL), U10 HD36790 (RTI International, Research Triangle Park,
NC), U10 HD40461 (University of California-San Diego, CA), U10 HD40492
(Duke University, Durham, NC), and U10 HD40498 (Wake Forest University,
Winston-Salem, NC).
NR 14
TC 17
Z9 18
U1 0
U2 3
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 JAN
PY 2012
VL 13
IS 1
BP 53
EP 59
DI 10.1097/PCC.0b013e31821926bc
PG 7
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 875YT
UT WOS:000299073000021
PM 21499182
ER
PT J
AU Ballard, ED
Bosk, A
Snyder, D
Pao, M
Bridge, JA
Wharff, EA
Teach, SJ
Horowitz, L
AF Ballard, Elizabeth D.
Bosk, Abigail
Snyder, Deborah
Pao, Maryland
Bridge, Jeffrey A.
Wharff, Elizabeth A.
Teach, Stephen J.
Horowitz, Lisa
TI Patients' Opinions About Suicide Screening in a Pediatric Emergency
Department
SO PEDIATRIC EMERGENCY CARE
LA English
DT Article
DE suicide risk; screening; qualitative; patient opinion
ID PRIMARY-CARE; RISK; FEASIBILITY; ADOLESCENTS; CAREGIVERS; IDEATION
AB Objective: Understanding how children react to suicide screening in an emergency department (ED) can inform implementation strategies. This qualitative study describes pediatric patients' opinions regarding suicide screening in that setting.
Methods: As part of a multisite instrument validation study, patients 10 to 21 years presenting with both psychiatric and nonpsychiatric complaints to an urban, tertiary care pediatric ED were recruited for suicide screening. Interviews with subjects included the question, "do you think ER nurses should ask kids about suicide/thoughts about hurting them-selves...why/why not?'' Responses were transcribed verbatim and uploaded into NVivo8.0 qualitative software for coding and content analysis.
Results: Of the 156 patients who participated in the study, 106 (68%) presented to the ED with nonpsychiatric complaints and 50 (32%) presented with psychiatric complaints. The patients' mean (SD) age was 14.6 (2.8) years (range, 10-21 years), and 56% of the sample was female. All patients answered the question of interest, and 149 (96%) of 156 patients supported the idea that nurses should ask youth about suicide in the ED. The 5 most frequently endorsed themes were as follows: (1) identification of youth at risk (31/156, 20%), (2) a desire to feel known and understood by clinicians (31/156, 20%), (3) connection of youth with help and resources (28/156, 18%), (4) prevention of suicidal behavior (25/156, 16%), and (5) lack of other individuals to speak with about these issues (19/156, 12%).
Conclusions: Pediatric patients in the ED support suicide screening after being asked a number of suicide-related questions. Further work should evaluate the impact of suicide screening on referral practices and link screening efforts with evidence-based interventions.
C1 [Ballard, Elizabeth D.; Bosk, Abigail; Snyder, Deborah; Pao, Maryland; Horowitz, Lisa] NIMH, Off Clin Director, Bethesda, MD 20892 USA.
[Ballard, Elizabeth D.] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Bridge, Jeffrey A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43210 USA.
[Bridge, Jeffrey A.] Ohio State Univ, Columbus, OH 43210 USA.
[Wharff, Elizabeth A.] Childrens Hosp Boston, Dept Psychiat, Boston, MA USA.
[Wharff, Elizabeth A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
RP Horowitz, L (reprint author), NIH, Bldg 10-CRC,6-5340, Bethesda, MD 20892 USA.
EM horowitzl@mail.nih.gov
FU NIMH National Institutes of Health; National Institute of Mental Health
FX The research for this article was supported by the Intramural Research
Program of the NIMH National Institutes of Health and the National
Institute of Mental Health.
NR 24
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Z9 4
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0749-5161
J9 PEDIATR EMERG CARE
JI Pediatr. Emerg. Care
PD JAN
PY 2012
VL 28
IS 1
BP 34
EP 38
DI 10.1097/PEC.0b013e31823f2315
PG 5
WC Emergency Medicine; Pediatrics
SC Emergency Medicine; Pediatrics
GA 876JW
UT WOS:000299104800009
PM 22193697
ER
PT J
AU Siberry, GK
Warshaw, MG
Williams, PL
Spector, SA
Decker, MD
Jean-Philippe, P
Yogev, R
Heckman, BE
Manzella, A
Roa, J
Nachman, S
Lujan-Zilbermann, J
AF Siberry, George K.
Warshaw, Meredith G.
Williams, Paige L.
Spector, Stephen A.
Decker, Michael D.
Jean-Philippe, Patrick
Yogev, Ram
Heckman, Barbara E.
Manzella, Adam
Roa, Jhoanna
Nachman, Sharon
Lujan-Zilbermann, Jorge
CA IMPAACT P1065 Protocol Team
TI Safety and Immunogenicity of Quadrivalent Meningococcal Conjugate
Vaccine in 2-to 10-year-old Human Immunodeficiency Virus-infected
Children
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE pediatric HIV infection; meningococcal vaccine; conjugate vaccine
ID ACTIVE ANTIRETROVIRAL THERAPY; POLYSACCHARIDE VACCINE; ADOLESCENTS;
PREDICTORS; TRIAL
AB Background: Human immunodeficiency virus (HIV)-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine (MCV4), but MCV4 has not been studied in preadolescent HIV-infected children.
Methods: The P1065 trial enrolled 2- to 10-year-old HIV-infected children with CD4 >= 25% to receive MCV4 at entry and at week 24. Rates of response (>= 4-fold increase in rabbit serum bactericidal antibody) against each meningococcal serogroup (A, C, Y, W-135), geometric mean titers, and rates of seroprotection (rabbit serum bactericidal antibody titer >= 1: 128) were determined from sera obtained at entry and weeks 4, 24, 28, and 72. Adverse events were assessed for 6 weeks after each MCV4 dose.
Results: At entry, 47% of the 59 participants were male, 56% black, 31% Latino, median age was 6 years, 88% were receiving antiretroviral therapy, and 75% had viral load <400 copies/mL. There were no serious adverse events within 6 weeks after MCV4 doses; all vaccination reactions were mild. Response after a single MCV4 dose was high to serogroup A (92%) and W-135 (98%); responses improved after a second dose for serogroup C (43%-80%) (P = 0.0001) and Y (76%-84%) (P = 0.38). By week 72, seroprotection rates were 93%, 91%, 78%, and 46% for serogroups W-135, Y, A, and C, respectively.
Conclusions: Two doses of MCV4 were safe and immunogenic in 2-to 10-year-old HIV-infected children. The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within 1 year of last MCV4 dose.
C1 [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, Bethesda, MD USA.
[Warshaw, Meredith G.; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, Div Infect Dis, San Diego, CA 92103 USA.
[Spector, Stephen A.] Rady Childrens Hosp San Diego, La Jolla, CA USA.
[Decker, Michael D.] Sanofi Pasteur Inc, Swiftwater, PA USA.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn Adv Mil Med, Div Aids, Bethesda, MD 20892 USA.
[Yogev, Ram] Childrens Mem Hosp, Sect Pediat Adolescent & Maternal HIV Infect, Chicago, IL 60614 USA.
[Heckman, Barbara E.; Manzella, Adam] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Roa, Jhoanna] Social & Sci Syst Inc, Silver Spring, MD USA.
[Nachman, Sharon] SUNY Stony Brook, Dept Pediat, Div Infect Dis, Stony Brook, NY 11794 USA.
[Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD USA.
EM siberryg@mail.nih.gov
OI Frenkel, Lisa M/0000-0001-9566-8959; Decker, Michael/0000-0003-1008-7472
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; Statistical and Data Analysis Center at Harvard School of
Public Health, under the National Institute of Allergy and Infectious
Diseases [5 U01 AI41110]; IMPAACT Group [1 U01 AI068616]; National
Institute of Allergy and Infectious Diseases (NIAID); NICHD
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network; NICHD [N01-DK-9-001/HHSN267200800001C]; National Institute of
Allergies and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services [HHSN272200800014C]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) (AI068632).
This work was supported by the Statistical and Data Analysis Center at
Harvard School of Public Health, under the National Institute of Allergy
and Infectious Diseases cooperative agreement 5 U01 AI41110 with the
Pediatric AIDS Clinical Trials Group (PACTG) and 1 U01 AI068616 with the
IMPAACT Group. Support of the sites was provided by the National
Institute of Allergy and Infectious Diseases (NIAID) and the NICHD
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network funded by NICHD (contract number
N01-DK-9-001/HHSN267200800001C). This project has also been supported
with Federal funds from the National Institute of Allergies and
Infectious Diseases, National Institutes of Health, Department of Health
and Human Services, under Contract No. HHSN272200800014C. Sanofi Pasteur
Inc. provided study vaccine and performed meningococcal serum
bactericidal antibody activity assays.
NR 19
TC 13
Z9 14
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JAN
PY 2012
VL 31
IS 1
BP 47
EP 52
DI 10.1097/INF.0b013e318236c67b
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 875QV
UT WOS:000299050100015
PM 21987006
ER
PT J
AU Alonso, WJ
Laranjeira, BJ
Pereira, SAR
Florencio, CMGD
Moreno, EC
Miller, MA
Giglio, R
Schuck-Paim, C
Moura, FEA
AF Alonso, Wladimir J.
Laranjeira, Bruno J.
Pereira, Samuel A. R.
Florencio, Caroline M. G. D.
Moreno, Eduardo C.
Miller, Mark A.
Giglio, Ricardo
Schuck-Paim, Cynthia
Moura, Fernanda E. A.
TI Comparative Dynamics, Morbidity and Mortality Burden of Pediatric Viral
Respiratory Infections in an Equatorial City
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE influenza; RSV; pneumonia; tropics; ARI
ID PARAINFLUENZA VIRUS-INFECTIONS; NORTHEASTERN BRAZIL; SEASONAL TRENDS;
CHILDREN; INFLUENZA; TROPICS
AB Background: Although acute respiratory infections (ARIs) are the global leading cause of pediatric morbidity and mortality, the relative impact of viral pathogens on pediatric ARIs is still poorly understood, especially in equatorial settings. Long-term studies of multiple viruses concurrently circulating in these regions are still lacking. Here, we report the results of a systematic prospective surveillance of multiple respiratory viruses conducted every weekday for nearly a decade in an equatorial city in Brazil.
Methods: We analyzed the relative burden of influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus, and metapneumovirus, their seasonality, and their association with climatic and demographic factors, ARI diagnosis, and pediatric mortality.
Results and Conclusions: RSV was the primary driver of severe childhood respiratory infections, including pneumonia. RSV was also the virus most strongly associated with respiratory-associated deaths, with RSV circulation and pediatric mortality being in phase. Annual circulation of influenza peaked much earlier than annual mortality due to respiratory causes. The results also show that viral circulation can be strongly seasonal even in equatorial regions, which lack seasons with low temperatures: RSV and influenza were concentrated in the rainy season, whereas parainfluenza predominantly circulated in the dry season. The consistent epidemiologic patterns observed can be used for an effective adjustment of the timing of therapeutic and prophylactic interventions in this and potentially in other equatorial regions.
C1 [Moura, Fernanda E. A.] Univ Fed Ceara, Fac Med, Dept Pathol & Med, Virol Lab, BR-60430270 Fortaleza, Ceara, Brazil.
[Alonso, Wladimir J.; Miller, Mark A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Giglio, Ricardo; Schuck-Paim, Cynthia] Origem Sci, Florianopolis, SC, Brazil.
RP Moura, FEA (reprint author), Univ Fed Ceara, Fac Med, Dept Pathol & Med, Virol Lab, Rua Coronel Nunes de Melo 1315, BR-60430270 Fortaleza, Ceara, Brazil.
EM fernandaedna@terra.com.br
RI Moura, Fernanda/I-2739-2013
FU Fogarty International Center, National Institutes of Health; Fundacao
Cearense de Apoio ao Desenvolvimento Cientifico e Tecnologico (FUNCAP);
FUNCAP; Multinational Influenza Seasonal Mortality Study; Office of
Global Health Affairs' International Influenza Unit (Department of
Health and Human Services)
FX M.A.M., supported by the Fogarty International Center, National
Institutes of Health; F.E.A.M., supported by Fundacao Cearense de Apoio
ao Desenvolvimento Cientifico e Tecnologico (FUNCAP); B.J.L. received a
PhD grant from FUNCAP; S.A.R.P., C.M.G.D.F., and E.C.M. received grants
from FUNCAP; W.J.A., supported by the Multinational Influenza Seasonal
Mortality Study, a project led by the Fogarty International Center (NIH)
and funded by the Office of Global Health Affairs' International
Influenza Unit (Department of Health and Human Services). The authors
have no other funding or conflicts of interest to disclose.
NR 24
TC 24
Z9 26
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JAN
PY 2012
VL 31
IS 1
BP E9
EP E14
DI 10.1097/INF.0b013e31823883be
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 875QV
UT WOS:000299050100002
PM 22001966
ER
PT J
AU Joehanes, R
Johnson, AD
Barb, JJ
Raghavachari, N
Liu, PC
Woodhouse, KA
O'Donnell, CJ
Munson, PJ
Levy, D
AF Joehanes, Roby
Johnson, Andrew D.
Barb, Jennifer J.
Raghavachari, Nalini
Liu, Poching
Woodhouse, Kimberly A.
O'Donnell, Christopher J.
Munson, Peter J.
Levy, Daniel
TI Gene expression analysis of whole blood, peripheral blood mononuclear
cells, and lymphoblastoid cell lines from the Framingham Heart Study
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE microarray; system biology; biomarker discovery; fingerprinting genes;
data normalization; X-linked expression; cardiovascular disease
ID EPSTEIN-BARR-VIRUS; MOLECULAR-GENETICS; IMMUNE-RESPONSES; LUNG-CANCER;
PROFILES; DISEASE; ASSOCIATION; BIOMARKERS; RECEPTORS; PATHWAYS
AB Joehanes R, Johnson AD, Barb JJ, Raghavachari N, Liu P, Woodhouse KA, O'Donnell CJ, Munson PJ, Levy D. Gene expression analysis of whole blood, peripheral blood mononuclear cells, and lymphoblastoid cell lines from the Framingham Heart Study. Physiol Genomics 44: 59-75, 2012. First published November 1, 2011; doi: 10.1152/physiolgenomics.00130.2011.-Despite a growing number of reports of gene expression analysis from blood-derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of cardiovascular disease (CVD). As a pilot study of the Systems Approach to Biomarker Research (SABRe) in CVD Initiative, this investigation used Affymetrix Exon arrays to characterize gene expression of three blood-derived RNA sources: lymphoblastoid cell lines (LCL), whole blood using PAXgene tubes (PAX), and peripheral blood mononuclear cells (PBMC). Their performance was compared in relation to identifying transcript associations with sex and CVD risk factors, such as age, high-density lipoprotein, and smoking status, and the differential blood cell count. We also identified a set of exons that vary substantially between participants, but consistently in each RNA source. Such exons are thus stable phenotypes of the participant and may potentially become useful fingerprinting biomarkers. In agreement with previous studies, we found that each of the RNA sources is distinct. Unlike PAX and PBMC, LCL gene expression showed little association with the differential blood count. LCL, however, was able to detect two genes related to smoking status. PAX and PBMC identified Y-chromosome probe sets similarly and slightly better than LCL.
C1 [Joehanes, Roby; Johnson, Andrew D.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Joehanes, Roby; Johnson, Andrew D.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Barb, Jennifer J.; Munson, Peter J.] NHLBI, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Liu, Poching; Woodhouse, Kimberly A.] NHLBI, DNA Sequencing & Genom Core, Genet & Dev Ctr, NIH, Bethesda, MD 20892 USA.
RP Levy, D (reprint author), NHLBI, Ctr Populat Studies, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM levyd@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013
FU National Institutes of Health [NO1-HC-25195]; Division of Intramural
Research, NHLBI, Bethesda, MD
FX The National Heart, Lung, and Blood Institute's (NHLBI's) FHS is
supported by National Institutes of Health Grant NO1-HC-25195. The SABRe
CVD Initiative is funded by the Division of Intramural Research, NHLBI,
Bethesda, MD.
NR 80
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Z9 21
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD JAN
PY 2012
VL 44
IS 1
BP 59
EP 75
DI 10.1152/physiolgenomics.00130.2011
PG 17
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 879HK
UT WOS:000299320100006
PM 22045913
ER
PT J
AU Westbroek, W
Klar, A
Cullinane, AR
Ziegler, SG
Hurvitz, H
Ganem, A
Wilson, K
Dorward, H
Huizing, M
Tamimi, H
Vainshtein, I
Berkun, Y
Lavie, M
Gahl, WA
Anikster, Y
AF Westbroek, Wendy
Klar, Aharon
Cullinane, Andrew R.
Ziegler, Shira G.
Hurvitz, Haggit
Ganem, Ashraf
Wilson, Kirkland
Dorward, Heidi
Huizing, Marjan
Tamimi, Haled
Vainshtein, Igor
Berkun, Yackov
Lavie, Moran
Gahl, William A.
Anikster, Yair
TI Cellular and clinical report of new Griscelli syndrome type III cases
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE Griscelli syndrome type III; Melanophilin; melanocyte; melanosome;
Myosin-5a; RAB27A; tripartite complex
ID SMALL GTPASE RAB27B; MYOSIN-VA; MELANOSOME TRANSPORT; HUMAN MELANOCYTES;
LINKS RAB27A; MELANOPHILIN; MUTATIONS; PROTEINS; SLAC2-A/MELANOPHILIN;
DISEASE
AB The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes for subsequent transfer to keratinocytes. Mutations in any one member of this tripartite complex cause three forms of Griscelli syndrome (GS), each with distinct clinical features but with a similar cellular phenotype. To date, only one case of GS type III (GSIII), caused by mutations in the Melanophilin (MLPH) gene, has been reported. Here, we report seven new cases of GSIII in three distinct Arab pedigrees. All affected individuals carried a homozygous missense mutation (c.102C>T; p.R35W), located in the conserved Slp homology domain of MLPH, and had hypomelanosis of the skin and hair. We report the first cellular studies on GSIII melanocytes, which demonstrated that MLPH(R35W) causes perinuclear aggregation of melanosomes in melanocytes, typical for GS. Additionally, co-immunoprecipitation assays showed that MLPH(R35W) lost its interaction with RAB27A, indicating pathogenicity of the R35W mutation.
C1 [Westbroek, Wendy; Cullinane, Andrew R.; Ziegler, Shira G.; Wilson, Kirkland; Dorward, Heidi; Huizing, Marjan; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Klar, Aharon; Hurvitz, Haggit; Ganem, Ashraf; Tamimi, Haled; Vainshtein, Igor] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pediat, Bikur Cholim Gen Hosp, IL-91010 Jerusalem, Israel.
[Berkun, Yackov; Lavie, Moran; Anikster, Yair] Edmond & Lily Safra Childrens Hosp, Metab Dis Unit, Sheba Med Ctr, Tel Hashomer, Israel.
[Berkun, Yackov; Lavie, Moran; Anikster, Yair] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
RP Westbroek, W (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM wwestbro@mail.nih.gov
RI Berkun, Yackov/A-1694-2009
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, Maryland, USA
FX We kindly acknowledge the patients and their families who participated
in this study. This research was supported by the Intramural Research
Program of the National Human Genome Research Institute, National
Institutes of Health, Bethesda, Maryland, USA.
NR 27
TC 10
Z9 10
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JAN
PY 2012
VL 25
IS 1
BP 47
EP 56
DI 10.1111/j.1755-148X.2011.00901.x
PG 10
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 869ED
UT WOS:000298577600009
PM 21883982
ER
PT J
AU Liu, WH
Onda, M
Kim, C
Xiang, LM
Weldon, JE
Lee, B
Pastan, I
AF Liu, Wenhai
Onda, Masanori
Kim, Changhoon
Xiang, Laiman
Weldon, John E.
Lee, Byungkook
Pastan, Ira
TI A recombinant immunotoxin engineered for increased stability by adding a
disulfide bond has decreased immunogenicity
SO PROTEIN ENGINEERING DESIGN & SELECTION
LA English
DT Article
DE disulfide bond; immunotoxin; immunogenicity
ID COMPUTER-AIDED-DESIGN; B-CELL EPITOPES; PHASE-I TRIAL; PSEUDOMONAS
EXOTOXIN; RFB4(DSFV)-PE38 BL22; HEMATOLOGIC MALIGNANCIES; CONFORMATIONAL
STABILITY; CANCER; TOXICITY; LYMPHOMA
AB Recombinant immunotoxins (RITs) are anti-cancer agents that combine the Fv of an antibody against cancer cells with a protein toxin from bacteria or plants. Since RITs contain a non-human protein, immunogenicity can be an obstacle in their development. In this study, we have explored the hypothesis that increasing stability can reduce the immunogenicity of a RIT using HA22-LR, which is composed of an anti-CD22 Fv fused to domain III of Pseudomonas exotoxin A. We introduced a disulfide bond into domain III by identifying and mutating two structurally adjacent residues to cysteines at sites suggested by computer modeling. This RIT, HA22-LR-DB, displays a remarkable increase in thermal stability and an enhanced resistance to trypsin degradation. In addition, HA22-LR-DB retains cytotoxic and anti-tumor activity, while exhibiting significantly lower immunogenicity in mice. This study demonstrates that it is possible to design mutations in a protein molecule that will increase the stability of the protein and thereby reduce its immunogenicity.
C1 [Liu, Wenhai; Onda, Masanori; Kim, Changhoon; Xiang, Laiman; Weldon, John E.; Lee, Byungkook; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
RI Lee, Byungkook/E-4564-2011; liu, wenhai/N-3783-2015;
OI Lee, Byungkook/0000-0002-3339-4582; Weldon, John/0000-0002-6516-9064
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 32
TC 15
Z9 15
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1741-0126
J9 PROTEIN ENG DES SEL
JI Protein Eng. Des. Sel.
PD JAN
PY 2012
VL 25
IS 1
BP 1
EP 6
DI 10.1093/protein/gzr053
PG 6
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 879RD
UT WOS:000299348700001
PM 22101015
ER
PT J
AU Shigunov, P
Sotelo-Silveira, J
Kuligovski, C
de Aguiar, AM
Rebelatto, CK
Moutinho, JA
Brofman, PS
Krieger, MA
Goldenberg, S
Munroe, D
Correa, A
Dallagiovanna, B
AF Shigunov, Patricia
Sotelo-Silveira, Jose
Kuligovski, Crisciele
de Aguiar, Alessandra Melo
Rebelatto, Carmen K.
Moutinho, Jose A.
Brofman, Paulo S.
Krieger, Marco A.
Goldenberg, Samuel
Munroe, David
Correa, Alejandro
Dallagiovanna, Bruno
TI PUMILIO-2 Is Involved in the Positive Regulation of Cellular
Proliferation in Human Adipose-Derived Stem Cells
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID RNA-BINDING PROTEINS; CAENORHABDITIS-ELEGANS; DROSOPHILA-PUMILIO;
MESSENGER-RNAS; SELF-RENEWAL; BONE-MARROW; GERM-CELLS; DIFFERENTIATION;
FAMILY; PUF-8
AB Stem cells can either differentiate into more specialized cells or undergo self-renewal. Several lines of evidence from different organisms suggest that these processes depend on the post-transcriptional regulation of gene expression. The presence of the PUF [Pumilio/FBF (fem-3 binding factor)] domain defines a conserved family of RNA binding proteins involved in repressing gene expression. It has been suggested that a conserved function of PUF proteins is to repress differentiation and sustain the mitotic proliferation of stem cells. In humans, Pumilio-2 (PUM2) is expressed in embryonic stem cells and adult germ cells. Here we show that PUM2 is expressed in a subpopulation of adipose-derived stem cell (ASC) cultures, with a granular pattern of staining in the cytoplasm. Protein levels of PUM2 showed no changes during the differentiation of ASCs into adipocytes. Moreover, RNAi knockdown of pum2 did not alter the rate of adipogenic differentiation compared with wild-type control cells. A ribonomic approach was used to identify PUM2-associated mRNAs. Microarray analysis showed that PUM2-bound mRNAs are part of gene networks involved in cell proliferation and gene expression control. We studied pum2 expression in cell cultures with low or very high levels of proliferation and found that changes in pum2 production were dependent on the proliferation status of the cell. Transient knockdown of pum2 expression by RNAi impaired proliferation of ASCs in vitro. Our results suggest that PUM2 does not repress differentiation of ASCs but rather is involved in the positive control of ASCs division and proliferation.
C1 [Shigunov, Patricia; Kuligovski, Crisciele; de Aguiar, Alessandra Melo; Krieger, Marco A.; Goldenberg, Samuel; Correa, Alejandro; Dallagiovanna, Bruno] Fiocruz MS, Lab Biol Basica Celulas Tronco, Inst Carlos Chagas, BR-81350010 Curitiba, Parana, Brazil.
[Sotelo-Silveira, Jose; Munroe, David] NCI, Adv Technol Program, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Sotelo-Silveira, Jose] Inst Invest Biol Clemente Estable, Dept Genet, Montevideo 11600, Uruguay.
[Sotelo-Silveira, Jose] UdelaR, Sch Sci, Dept Cell & Mol Biol, Montevideo, Uruguay.
[Rebelatto, Carmen K.; Brofman, Paulo S.] Pontificia Univ Catolica Parana, Nucleo Cardiomioplastia Celular, Curitiba, Parana, Brazil.
[Moutinho, Jose A.] Inst Med & Cirurgia Parana, Curitiba, Parana, Brazil.
RP Dallagiovanna, B (reprint author), Fiocruz MS, Lab Biol Basica Celulas Tronco, Inst Carlos Chagas, Rua Algacyr Munhoz Mader 3775, BR-81350010 Curitiba, Parana, Brazil.
EM sotelojos@gmail.com; brunod@tecpar.br
RI GOLDENBERG, SAMUEL/B-4116-2009; Aguiar, Alessandra /B-4899-2010; P,
CM/B-1358-2013; Saude Publica, Inct/J-9544-2013
OI GOLDENBERG, SAMUEL/0000-0002-4892-163X; Aguiar, Alessandra
/0000-0002-6167-8478;
FU Ministerio da Saude; Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico-CNPq (CT-Saude/MS/SCTIE/DECIT/MCT/CNPq) [17/2008]; National
Cancer Institute, National Institutes of Health [HSN261200800001E];
CNPq; CAPES
FX We thank Marco Stimamiglio and Alexandra C. Senegaglia for scientific
advice and helpful discussions. This work was supported by grants from
Ministerio da Saude and Conselho Nacional de Desenvolvimento Cientifico
e Tecnologico-CNPq (CT-Saude/MS/SCTIE/DECIT/MCT/CNPq No. 17/2008). This
project has been funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
HSN261200800001E. The content of this article 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. M.A.K., S.G.,
and B.D. received fellowships from CNPq and P.S. from CAPES.
NR 36
TC 5
Z9 5
U1 0
U2 4
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 JAN
PY 2012
VL 21
IS 2
BP 217
EP 227
DI 10.1089/scd.2011.0143
PG 11
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 877GF
UT WOS:000299164600006
PM 21649561
ER
PT J
AU Ayres, DL
Darling, A
Zwickl, DJ
Beerli, P
Holder, MT
Lewis, PO
Huelsenbeck, JP
Ronquist, F
Swofford, DL
Cummings, MP
Rambaut, A
Suchard, MA
AF Ayres, Daniel L.
Darling, Aaron
Zwickl, Derrick J.
Beerli, Peter
Holder, Mark T.
Lewis, Paul O.
Huelsenbeck, John P.
Ronquist, Fredrik
Swofford, David L.
Cummings, Michael P.
Rambaut, Andrew
Suchard, Marc A.
TI BEAGLE: An Application Programming Interface and High-Performance
Computing Library for Statistical Phylogenetics
SO SYSTEMATIC BIOLOGY
LA English
DT Article
DE Bayesian phylogenetics; GPU; maximum likelihood; parallel computing
ID SEQUENCES
AB Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software.
C1 [Ayres, Daniel L.; Cummings, Michael P.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Darling, Aaron] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA.
[Zwickl, Derrick J.; Holder, Mark T.] Univ Kansas, Dept Ecol & Evolutionary Biol, Lawrence, KS 66045 USA.
[Beerli, Peter] Florida State Univ, Dept Comp Sci, Tallahassee, FL 32306 USA.
[Huelsenbeck, John P.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Lewis, Paul O.] Univ Connecticut, Dept Ecol & Evolutionary Biol, Storrs, CT 06269 USA.
[Ronquist, Fredrik] Swedish Museum Nat Hist, S-11418 Stockholm, Sweden.
[Swofford, David L.] Duke Univ, Inst Genome Sci & Policy, Ctr Evolutionary Genom, Durham, NC 27708 USA.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolut Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA.
RP Ayres, DL (reprint author), Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
EM ayres@umiacs.umd.edu; a.rambaut@ed.ac.uk; msuchard@ucla.edu
RI Huelsenbeck, John/C-6398-2013; Research, NRM-BIG/F-2603-2013; Beerli,
Peter/A-3638-2009; Ronquist, Fredrik/Q-2013-2015;
OI Beerli, Peter/0000-0003-0947-5451; Holder, Mark/0000-0001-5575-0536;
Rambaut, Andrew/0000-0003-4337-3707; Darling, Aaron/0000-0003-2397-7925
FU National Science Foundation [DBI-0755048, DEB-0732920, DEB-1036448,
DMS-0931642, EF-0331495, EF-0905606, EF-0949453]; National Institutes of
Health [R01-HG006139, R01-GM037841, R01-GM078985, R01-GM086887,
R01-NS063897]; Biotechnology and Biological Sciences Research Council
[BB/ H011285/1]; Wellcome Trust [WT092807MA]; Google Summer of Code
FX This work was supported by the National Science Foundation [grant
numbers DBI-0755048, DEB-0732920, DEB-1036448, DMS-0931642, EF-0331495,
EF-0905606, EF-0949453]; the National Institutes of Health [grant
numbers R01-HG006139, R01-GM037841, R01-GM078985, R01-GM086887,
R01-NS063897]; the Biotechnology and Biological Sciences Research
Council [grant number BB/ H011285/1]; the Wellcome Trust [grant number
WT092807MA]; and Google Summer of Code.
NR 7
TC 103
Z9 104
U1 4
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1063-5157
EI 1076-836X
J9 SYST BIOL
JI Syst. Biol.
PD JAN
PY 2012
VL 61
IS 1
BP 170
EP 173
DI 10.1093/sysbio/syr100
PG 4
WC Evolutionary Biology
SC Evolutionary Biology
GA 877PZ
UT WOS:000299195700013
PM 21963610
ER
PT J
AU Chen, XY
AF Chen, Xiaoyuan (Shawn)
TI One Year after a Successful Start of Theranostics
SO THERANOSTICS
LA English
DT Editorial Material
DE Theranostics; journal
AB As Theranostics begins its second year of publication, I would like to thank our authors, reviewers, and audience for their outstanding support in 2011. I look forward to working with you in 2012 to continue our mission to distinguish Theranostics as a leader of publishing cutting edge research in this important and emerging field.
C1 Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM Shawn.Chen@nih.gov
NR 0
TC 4
Z9 4
U1 1
U2 3
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2012
VL 2
IS 1
BP 1
EP 2
DI 10.7150/thno.2.1
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 876PZ
UT WOS:000299121200001
PM 22272216
ER
PT J
AU Ma, DY
Assumpcao, TCF
Li, Y
Andersen, JF
Ribeiro, JMC
Francischetti, IMB
AF Ma, Dongying
Assumpcao, Teresa C. F.
Li, Yuan
Andersen, John F.
Ribeiro, Jose M. C.
Francischetti, Ivo M. B.
TI Triplatin, a platelet aggregation inhibitor from the salivary gland of
the triatomine vector of Chagas disease, binds to TXA(2) but does not
interact with glycoprotein PVI
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Snake venoms; protein function / activity; platelet physiology
ID APOLIPOPROTEIN-D; THROMBUS FORMATION; RHODNIUS-PROLIXUS; COLLAGEN
RECEPTOR; HISTAMINE-BINDING; ARACHIDONIC-ACID; PROTEINS; ACTIVATION;
MECHANISM; CLONING
AB Salivary glands from haematophagous animals express a notable diversity of negative modulators of platelet function. Triplatin is an inhibitor of collagen-induced platelet aggregation which has been described as an antagonist of glycoprotein VI (GPVI). Because triplatin displays sequence homology to members of the lipocalin family of proteins, we investigated whether triplatin mechanism of action could be explained by interaction with pro-haemostatic prostaglandins. Our results demonstrate that triplatin inhibits platelet aggregation induced by low doses of collagen, thromboxane A2 (TXA(2)) mimetic (U46619), and arachidonic acid (AA). On the other hand, it does not inhibit platelet aggregation by convulxin, PMA, or low-dose ADP. Isothermal titration calorimetry (ITC) revealed that triplatin binds AA, cTXA(2), TXB2, U46619 or prostaglandin (PG)H-2 mimetic (U51605). Consistent with its ligand specificity, triplatin induces relaxation of rat aorta contracted with U46619. Triplatin also interacts with PGF(2 alpha) and PGJ(2), but not with leukotrienes, AA or biogenic amines. Surface plasmon resonance experiments failed to demonstrate interaction of triplatin with GPVI; it also did to inhibit platelet adhesion to fibrillar or soluble collagen. Because triplatin displays sequence similarity to apolipoprotein D (ApoD) - a lipocalin associated with high-density lipoprotein, ApoD was tested as a putative TXA(2)-binding molecule. ITC failed to demonstrate binding of ApoD to all prostanoids described above, or to AA. Furthermore, ApoD was devoid of inhibitory properties towards platelets activation by AA, collagen, or U46619. In conclusion, triplatin mechanism of action has been elucidated without ambiguity as a novel TXA(2)- and PGF(2 alpha)- binding protein. It conceivably blocks platelet aggregation and vasoconstriction, thus contributing to successful blood feeding at the vector-host interface.
C1 [Ma, Dongying; Assumpcao, Teresa C. F.; Li, Yuan; Andersen, John F.; Ribeiro, Jose M. C.; Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Francischetti, IMB (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Rm 2E28, Rockville, MD 20852 USA.
EM ifrancischetti@niaid.nih.goy
RI ma, dongying/D-8623-2012; Ribeiro, Jose/J-7011-2015
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank NIAID
intramural editor Brenda Rae Marshall for assistance. We thank Dr.
Jean-Luc Villeval (INSERM, France) for providing recombinant GPVI, Drs.
Glenn Nardone (NIAID) for mass spectrometry results and Mark Garfield
(NIAID) for identification of the N-terminus of triplatin. Because JA,
JR and IF are government employees and this is a government work, the
work is in the public domain in the United States. Notwithstanding any
other agreements, the NIH reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices. You can
establish rights outside of the U.S. subject to a government use
license.
NR 50
TC 8
Z9 9
U1 2
U2 13
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JAN
PY 2012
VL 107
IS 1
BP 111
EP 123
DI 10.1160/TH11-10-0685
PG 13
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 879UO
UT WOS:000299357900017
PM 22159626
ER
PT J
AU Nair, S
Muller, YL
Ortega, E
Kobes, S
Bogardus, C
Baier, LJ
AF Nair, Saraswathy
Muller, Yunhua Li
Ortega, Emilio
Kobes, Sayuko
Bogardus, Clifton
Baier, Leslie J.
TI Association Analyses of Variants in the DIO2 Gene with Early-Onset Type
2 Diabetes Mellitus in Pima Indians
SO THYROID
LA English
DT Article
ID DEIODINASE THR92ALA POLYMORPHISM; THYROID-HORMONE; INSULIN-RESISTANCE;
IODOTHYRONINE DEIODINASE; ENERGY-EXPENDITURE; HYPOTHYROIDISM;
METABOLISM; RECEPTOR; OBESITY; HYPERINSULINEMIA
AB Background: The type 2 deiodinase gene (DIO2) encodes a deiodinase that converts the thyroid prohormone, thyroxine, to the biologically active triiodothyronine. Thyroid hormones regulate energy balance and may also influence glucose metabolism. Therefore, we hypothesized that variations in DIO2 could contribute to obesity or type 2 diabetes mellitus (T2DM) in Pima Indians.
Methods: Sequencing of the DIO2 gene in DNA from 83 Pima Indians identified 12 single-nucleotide polymorphisms (SNPs). Several of these SNPs were in perfect genotypic concordance among the 83 samples that were sequenced, and all 12 could be divided into five linkage disequilibrium groups. One representative SNP from each group (Thr92Ala, rs225011, rs225015, rs6574549, and a rare 5' flanking SNP) was selected for further genotyping for association analyses. In this study, the five selected variants in DIO2, as described above, were genotyped in three groups of Pima Indians: (i) a case (n = 150)/control (n = 150) group for early-onset T2DM (onset age < 25 years); (ii) a case (n = 362)/control (n = 127) group for obesity; (iii) a large (n = 1,311, cases n = 810/controls n = 501) family-based group, of which 256 nondiabetic subjects had undergone detailed metabolic phenotyping.
Results: The Thr92Ala variant common in Pima Indians, rs225011, and rs225015 were modestly associated with early-onset T2DM (p = 0.01-0.04) in the case-control study, but were not associated with obesity in the obesity case-control study, nor associated with T2DM (at any age) or body-mass index (BMI; as a quantitative trait) in the family-based analysis. Thr92Ala, rs225011, rs225015, and rs6574549 were also nominally associated with hepatic glucose output (p = 0.02). rs6574549 was associated with fasting insulin (p = 0.02), insulin action (p = 0.04), and energy expenditure (p = 0.02). None of these nominal associations remained statistically significant after corrections for multiple testing.
Conclusions: We propose that variation in DIO2 may have a subtle role in altering metabolic processes that lead to early-onset T2DM, but this gene does not have a large impact on T2DM at older ages, nor does DIO2 influence BMI in the Pima Indian population.
C1 [Nair, Saraswathy] Univ Texas Brownsville, Dept Biol Sci, Brownsville, TX 78520 USA.
[Nair, Saraswathy; Muller, Yunhua Li; Ortega, Emilio; Kobes, Sayuko; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Ortega, Emilio] Hosp Clin Barcelona, ICMDM, Dept Endocrinol & Diabet, Barcelona, Spain.
[Ortega, Emilio] Univ Barcelona, Barcelona, Spain.
RP Nair, S (reprint author), Univ Texas Brownsville, Dept Biol Sci, LHSB 1-824,80 Ft Brown, Brownsville, TX 78520 USA.
EM saraswathy.nair@utb.edu
FU National Institute of Health, NIDDK
FX The authors gratefully acknowledge the volunteers and leaders of the
Gila River Indian Community, whose cooperation made these studies
possible. The authors also acknowledge Dr. Joy Bunt and the nurses of
the Clinical Research Center, and Dr. Arline Salbe and the Metabolic
Kitchen staff, for the care of the research volunteers. The authors
sincerely thank Dr. Robert Hanson for performing the power analyses, as
well as help in conducting the multiple testing corrections in this
study. This research was supported by the Intramural Research Program of
the National Institute of Health, NIDDK.
NR 42
TC 10
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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 JAN
PY 2012
VL 22
IS 1
BP 80
EP 87
DI 10.1089/thy.2010.0455
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 876NI
UT WOS:000299113900012
PM 22142372
ER
PT J
AU Suhasini, AN
Brosh, RM
AF Suhasini, Avvaru N.
Brosh, Robert M., Jr.
TI Fanconi anemia and Bloom's syndrome crosstalk through FANCJ-BLM helicase
interaction
SO TRENDS IN GENETICS
LA English
DT Review
ID SISTER-CHROMATID EXCHANGES; MAINTAIN GENOME STABILITY; REPLICATION
PROTEIN-A; STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; LINK REPAIR;
DNA-REPAIR; HUMAN-CELLS; SUMO MODIFICATION; RECQ HELICASES
AB Fanconi anemia (FA) and Bloom's syndrome (BS) are rare hereditary chromosomal instability disorders. FA displays bone marrow failure, acute myeloid leukemia, and head and neck cancers, whereas BS is characterized by growth retardation, immunodeficiency, and a wide spectrum of cancers. The BLM gene mutated in BS encodes a DNA helicase that functions in a protein complex to suppress sister-chromatid exchange. Of the 15 FA genetic complementation groups implicated in interstrand crosslink repair, FANCJ encodes a DNA helicase involved in recombinational repair and replication stress response. Based on evidence that BLM and FANCJ interact we suggest that crosstalk between BLM and FA pathways is more complex than previously thought. We propose testable models for how FANCJ and BLM coordinate to help cells deal with stalled replication forks or double-strand breaks (DSB). Understanding how BLM and FANCJ cooperate will help to elucidate an important pathway for maintaining genomic stability.
C1 [Suhasini, Avvaru N.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU NIH; National Institute on Aging; Fanconi Anemia Research Fund
FX This work was supported by the Intramural Research program of the NIH,
National Institute on Aging, and the Fanconi Anemia Research Fund
(R.M.B.).
NR 70
TC 26
Z9 26
U1 2
U2 9
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD JAN
PY 2012
VL 28
IS 1
BP 7
EP 13
DI 10.1016/j.tig.2011.09.003
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 879XV
UT WOS:000299367100002
PM 22024395
ER
PT J
AU Ward, JM
Elmore, SA
Foley, JF
AF Ward, J. M.
Elmore, S. A.
Foley, J. F.
TI Pathology Methods for the Evaluation of Embryonic and Perinatal
Developmental Defects and Lethality in Genetically Engineered Mice
SO VETERINARY PATHOLOGY
LA English
DT Article
DE mouse embryo; embryonic lethality; placenta; histology atlas; imaging;
phenotyping
ID MOUSE PLACENTA; VIRTUAL HISTOLOGY; STAINING METHODS; MURINE; MORPHOLOGY;
EXPRESSION; ATLAS; RAS; DEFICIENCY; ACTIVATION
AB The normal embryonic development of organs and other tissues in mice and all species is preprogrammed by genes. Inactivation of a gene involved in any stage of normal embryonic development can have severe consequences leading to embryonic or postnatal developmental defects and lethality. Pathology methods are reviewed for evaluating normal and abnormal placenta and embryo, especially after E12.5. These methods include pathology protocols for necropsy and histopathology in addition to references that will provide additional knowledge for embryo assessment including histology atlases and advanced embryo imaging techniques.
C1 [Ward, J. M.] Global VetPathol, Montgomery Village, MD 20886 USA.
[Elmore, S. A.; Foley, J. F.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Ward, JM (reprint author), Global VetPathol, Montgomery Village, MD 20886 USA.
EM globalvetpathology@gmail.com
FU National Institute of Environmental Health Sciences, National Institutes
of Health
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported, in part, by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health.
NR 52
TC 4
Z9 4
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD JAN
PY 2012
VL 49
IS 1
BP 71
EP 84
DI 10.1177/0300985811429811
PG 14
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 872ZW
UT WOS:000298851100008
PM 22146849
ER
PT J
AU He, YL
Korboukh, I
Jin, J
Huang, J
AF He, Yunlong
Korboukh, Ilia
Jin, Jian
Huang, Jing
TI Targeting protein lysine methylation and demethylation in cancers
SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA
LA English
DT Review
DE methylation; demethylation; methyltransferase; demethylase; cancer;
epigenetics
ID NF-KAPPA-B; G9A HISTONE METHYLTRANSFERASE; DOMAIN-CONTAINING PROTEINS;
BREAST-CANCER; TRANSCRIPTIONAL REPRESSION; SELECTIVE INHIBITORS;
CELL-PROLIFERATION; STRUCTURAL BASIS; PROSTATE-CANCER; SILENCED GENES
AB During the last decade, we saw an explosion of studies investigating the role of lysine methylation/demethylation of histones and non-histone proteins, such as p53, NF-kappaB, and E2F1. These 'Ying-Yang' post-translational modifications are important to fine-tuning the activity of these proteins. Lysine methylation and demethylation are catalyzed by protein lysine methyl-transferases (PKMTs) and protein lysine demethylases (PKDMs). PKMTs, PKDMs, and their substrates have been shown to play important roles in cancers. Although the underlying mechanisms of tumorigenesis are still largely unknown, growing evidence is starting to link aberrant regulation of methylation to tumorigenesis. This review focuses on summarizing the recent progress in understanding of the function of protein lysine methylation, and in the discovery of small molecule inhibitors for PKMTs and PKDMs. We also discuss the potential and the caveats of targeting protein lysine methylation for the treatment of cancer.
C1 [Korboukh, Ilia; Jin, Jian] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC 27599 USA.
[He, Yunlong; Huang, Jing] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Jin, J (reprint author), Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC 27599 USA.
EM jianjin@email.unc.edu; huangj3@mail.nih.gov
RI Huang, Jing/A-2566-2009; He, Yunlong/D-1278-2017
OI Huang, Jing/0000-0002-7163-5156;
FU Center for Cancer Research (CCR); National Cancer Institute; National
Institutes of Health, USA; University Cancer Research Fund (UCRF);
University of North Carolina at Chapel Hill
FX This work was supported by the grants from the Intramural Research
Program at the Center for Cancer Research (CCR), the National Cancer
Institute and the National Institutes of Health, USA for J.H., the
University Cancer Research Fund (UCRF) and the Carolina Partnership from
the University of North Carolina at Chapel Hill for J.J. and I.K.
NR 101
TC 27
Z9 29
U1 2
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1672-9145
J9 ACTA BIOCH BIOPH SIN
JI Acta Biochim. Biophys. Sin.
PD JAN
PY 2012
VL 44
IS 1
SI SI
BP 70
EP 79
DI 10.1093/abbs/gmr109
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 866NB
UT WOS:000298386700008
PM 22194015
ER
PT J
AU Brzezinski, K
Lazny, R
Sienkiewicz, M
Wojtulewski, S
Dauter, Z
AF Brzezinski, Krzysztof
Lazny, Ryszard
Sienkiewicz, Michal
Wojtulewski, Slawomir
Dauter, Zbigniew
TI (2R)-8-Benzyl-2-[(S)-hydroxy(phenyl)methyl]-8-azabicyclo[3.2.1]octan-3-o
ne
SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE
LA English
DT Article
ID ALDOL
AB The crystal of the title compound, C21H23NO2, was chosen from a conglomerate formed by a racemic mixture. An intramolecular hydrogen bond is formed between hydroxy group and heterocyclic N atom of the azabicyclo[ 3.2.1] octan-3-one system. The crystal structure is stabilized by C-H center dot center dot center dot O interactions between aliphatic C-H groups and the carbonyl O atom. For the title chiral crystal, the highly redundant and accurate diffraction data set collected with low energy copper radiation gave a Flack parameter of 0.12 (18) for anomalous scattering effects originating from O atoms.
C1 [Brzezinski, Krzysztof; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA.
[Lazny, Ryszard; Sienkiewicz, Michal; Wojtulewski, Slawomir] Univ Bialystok, Inst Chem, PL-15399 Bialystok, Poland.
RP Brzezinski, K (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Bldg 202, Argonne, IL 60439 USA.
EM kbrzezinski@anl.gov
FU University of Bialystok [BST-125]; Polish Ministry of Science and Higher
Education [N N204 546939]; NIH, National Cancer Institute, Center for
Cancer Research; National Cancer Institute, National Institutes of
Health [HHSN2612008000001E]
FX This work was supported in part by the University of Bialystok
(BST-125), the Polish Ministry of Science and Higher Education (grant
No. N N204 546939), the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research, and with Federal funds
from the National Cancer Institute, National Institutes of Health, under
contract HHSN2612008000001E.
NR 10
TC 6
Z9 6
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-5368
J9 ACTA CRYSTALLOGR E
JI Acta Crystallogr. Sect. E.-Struct Rep. Online
PD JAN
PY 2012
VL 68
DI 10.1107/S1600536811053190
PN 1
PG 11
WC Crystallography
SC Crystallography
GA 874NX
UT WOS:000298966400060
PM 22259435
ER
PT J
AU Montine, TJ
Phelps, CH
Beach, TG
Bigio, EH
Cairns, NJ
Dickson, DW
Duyckaerts, C
Frosch, MP
Masliah, E
Mirra, SS
Nelson, PT
Schneider, JA
Thal, DR
Trojanowski, JQ
Vinters, HV
Hyman, BT
AF Montine, Thomas J.
Phelps, Creighton H.
Beach, Thomas G.
Bigio, Eileen H.
Cairns, Nigel J.
Dickson, Dennis W.
Duyckaerts, Charles
Frosch, Matthew P.
Masliah, Eliezer
Mirra, Suzanne S.
Nelson, Peter T.
Schneider, Julie A.
Thal, Dietmar Rudolf
Trojanowski, John Q.
Vinters, Harry V.
Hyman, Bradley T.
TI National Institute on Aging-Alzheimer's Association guidelines for the
neuropathologic assessment of Alzheimer's disease: a practical approach
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
ID BRAINNET EUROPE CONSORTIUM; LEWY BODY DISEASE; FRONTOTEMPORAL LOBAR
DEGENERATION; VASCULAR COGNITIVE IMPAIRMENT; CEREBRAL AMYLOID
ANGIOPATHY; HIPPOCAMPAL SCLEROSIS; DIAGNOSTIC GUIDELINES; SYNAPSE LOSS;
NEUROFIBRILLARY PATHOLOGY; CONSENSUS RECOMMENDATIONS
AB We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an "ABC" score for AD neuropathologic change that incorporates histopathologic assessments of amyloid beta deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations.
C1 [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Phelps, Creighton H.] NIA, Bethesda, MD 20892 USA.
[Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA.
[Bigio, Eileen H.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Bigio, Eileen H.] Northwestern Univ, NW Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
[Cairns, Nigel J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Duyckaerts, Charles] Hop La Pitie Salpetriere, Serv Neuropathol Raymond Escourolle, Paris, France.
[Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA.
[Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA.
[Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA.
[Mirra, Suzanne S.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA.
[Nelson, Peter T.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
[Schneider, Julie A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Dept Pathol, Chicago, IL 60612 USA.
[Schneider, Julie A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Thal, Dietmar Rudolf] Univ Ulm, Neuropathol Lab, Inst Pathol, Ulm, Germany.
[Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
[Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA USA.
[Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Hyman, Bradley T.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Montine, TJ (reprint author), Univ Washington, Sch Med, Dept Pathol, Box 359791, Seattle, WA 98104 USA.
EM tmontine@uw.edu
OI Dickson, Dennis W/0000-0001-7189-7917
FU National Institute on Aging [AG05134, AG05136, AG03991, AG05681,
AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684,
AG15819, AG12435, AG05131, AG016976, AG16570, AG15866, AG18840];
Alzheimer's Association; Arizona Department of Health Services [211002];
Deutsche Forschungsgemeinschaft (DFG) [TH-624-4-1]; Alzheimer Forschung
Initiative (AFI) [10810]; Nancy and Buster Alvord Endowment; Charles and
Joanne Knight Alzheimer Research Initiative
FX Support was provided by the National Institute on Aging (AG05134,
AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124,
AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976,
AG16570, AG15866 and AG18840) as well as the Alzheimer's Association,
Arizona Department of Health Services (contract 211002, Arizona
Alzheimer's Consortium), Deutsche Forschungsgemeinschaft (DFG
TH-624-4-1) and Alzheimer Forschung Initiative (AFI #10810), the Nancy
and Buster Alvord Endowment, and the Charles and Joanne Knight Alzheimer
Research Initiative. We thank Dr. Joshua Sonnen for providing some
photomicrographs. The authors extend their deepest thanks to Dr. Heiko
Braak, Dr. Kelly Del Tredici, Dr. Nina Silverberg, Dr. Walter Kukull,
Dr. Kathleen Montine, Dr. Cerise Elliott, Dr. Bill Thies, Dr. Maria C.
Carrillo, and Ms. Sarah Monsell for their valuable input.
NR 64
TC 420
Z9 422
U1 6
U2 38
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD JAN
PY 2012
VL 123
IS 1
BP 1
EP 11
DI 10.1007/s00401-011-0910-3
PG 11
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 870BF
UT WOS:000298643400001
PM 22101365
ER
PT J
AU Gamaleddin, I
Wertheim, C
Zhu, AZX
Coen, KM
Vemuri, K
Makryannis, A
Goldberg, SR
Le Foll, B
AF Gamaleddin, Islam
Wertheim, Carrie
Zhu, Andy Z. X.
Coen, Kathleen M.
Vemuri, Kiran
Makryannis, Alex
Goldberg, Steven R.
Le Foll, Bernard
TI Cannabinoid receptor stimulation increases motivation for nicotine and
nicotine seeking
SO ADDICTION BIOLOGY
LA English
DT Article
DE Cannabinoid; discrimination; nicotine; relapse; self-administration; WIN
55; 212-2
ID CONDITIONED PLACE PREFERENCES; PROGRESSIVE RATIO SCHEDULE;
DISCRIMINATIVE-STIMULUS; ENDOCANNABINOID SYSTEM; ANANDAMIDE HYDROLYSIS;
CB1 RECEPTORS; MODULATION; ADDICTION; COCAINE; REINFORCEMENT
AB The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212-2, a CB1/2 agonist, on intravenous nicotine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212-2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212-2 on nicotine- and cue-induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212-2 on nicotine discrimination. WIN 55,212-2 decreased nicotine self-administration under the FR schedule. However, co-administration of WIN 55,212-2 with nicotine decreased responding for food, which suggests that this effect was non-selective. In contrast, WIN 55,212-2 increased both nicotine self-administration and responding for food under the PR schedule, produced dose-dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine-associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4 mg/kg nicotine, WIN 55,212-2 produced no nicotine-like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1-receptor-dependent mechanism. These findings indicate that cannabinoid CB1-receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine-seeking behaviour in abstinent subjects. Thus, modulating CB1-receptor signalling might have therapeutic value for treating nicotine dependence.
C1 [Gamaleddin, Islam; Zhu, Andy Z. X.; Coen, Kathleen M.; Le Foll, Bernard] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada.
[Wertheim, Carrie; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Pharmacol, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Toxicol, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Ctr Addict & Mental Hlth, Addict Program, Toronto, ON M5S 2S1, Canada.
[Vemuri, Kiran; Makryannis, Alex] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA.
RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada.
EM bernard_lefoll@camh.net
RI Le Foll, Bernard/K-2952-2014
OI Le Foll, Bernard/0000-0002-6406-4973
FU Egyptian Ministry of Higher Education-Ain Shams University; NIDA, NIH,
DHHS
FX This research was supported by the Egyptian Ministry of Higher
Education-Ain Shams University, the Intramural Research Program of NIDA,
NIH, DHHS.
NR 53
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U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JAN
PY 2012
VL 17
IS 1
BP 47
EP 61
DI 10.1111/j.1369-1600.2011.00314.x
PG 15
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 865HW
UT WOS:000298303000004
PM 21521420
ER
PT J
AU Kuzmin, A
Liljequist, S
Meis, J
Chefer, V
Shippenberg, T
Bakalkin, G
AF Kuzmin, Alexander
Liljequist, Sture
Meis, Jennifer
Chefer, Vladimir
Shippenberg, Toni
Bakalkin, Georgy
TI Repeated moderate-dose ethanol bouts impair cognitive function in Wistar
rats
SO ADDICTION BIOLOGY
LA English
DT Article
DE Animal model; behavioral flexibility; binge drinking; cognitive
impairment; ethanol; rat; spatial learning
ID ALCOHOL-CONSUMPTION; MEMORY DEFICITS; BINGE DRINKING; BARNES MAZE;
WITHDRAWAL; EXPOSURE; RECOVERY; RISK; NEUROTOXICITY; PERFORMANCE
AB The effects of repeated, intermittent administration of a moderate dose of ethanol (3.4 g/kg/day x 6 days, intragastrically via gavages) on cognitive function were examined in male Wistar rats. No significant differences in weight gain between the ethanol- and water-treated rats were found. Analysis of physical dependence revealed no signs of spontaneous withdrawal, whereas withdrawal signs exacerbated by Ro15-4513, an inverse benzodiazepine agonist, were apparent 5 hours but not 24 hours after the cessation of ethanol treatment. Spatial learning and memory, as assessed in the Barnes maze, were impaired 36 days following the treatment but recovered by the 11th14th days. Reversal learning, however, was impaired throughout the 2-week observation period. Thus, bouts of moderate-dose ethanol administration transiently impair spatial learning and memory, and promote cognitive inflexibility. The employed ethanol exposure paradigm may provide a model of human cognitive deficits associated with alcohol binge drinking.
C1 [Kuzmin, Alexander; Bakalkin, Georgy] Uppsala Univ, Div Biol Res Drug Dependence, Dept Pharmaceut Biosci, Uppsala, Sweden.
[Kuzmin, Alexander; Liljequist, Sture] Karolinska Inst, Dept Clin Neurosci, Sect Mol & Behav Neurosci, S-10401 Stockholm, Sweden.
[Meis, Jennifer; Chefer, Vladimir; Shippenberg, Toni] Natl Inst Drug Abuse, Integrat Neurosci Sect, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bakalkin, G (reprint author), Uppsala Univ, Div Biol Res Drug Dependence, Dept Pharmaceut Biosci, Uppsala, Sweden.
EM georgy.bakalkin@farmbio.uu.se
OI Bakalkin, Georgy/0000-0002-8074-9833
FU Swedish Council for Working Life and Social Research (FAS); AFA
Forsakring; Swedish Science Research Council; Alcohol Research Council
of the Swedish Retailing Monopoly; Uppsala University; Karolinska
Institutet
FX This work was supported by grants from the Swedish Council for Working
Life and Social Research (FAS), AFA Forsakring, Swedish Science Research
Council, Alcohol Research Council of the Swedish Retailing Monopoly, and
funds from Uppsala University and Karolinska Institutet.
NR 39
TC 10
Z9 10
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JAN
PY 2012
VL 17
IS 1
BP 132
EP 140
DI 10.1111/j.1369-1600.2010.00224.x
PG 9
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 865HW
UT WOS:000298303000011
PM 22026443
ER
PT J
AU Minkowski, CP
Epstein, D
Frost, JJ
Gorelick, DA
AF Minkowski, Carolynne P.
Epstein, David
Frost, J. James
Gorelick, David A.
TI Differential response to IV carfentanil in chronic cocaine users and
healthy controls
SO ADDICTION BIOLOGY
LA English
DT Article
DE Agonist; carfentanil; cocaine; mu-opioid receptor; PET scan; receptor
ID OPIOID RECEPTOR-BINDING; PREPROENKEPHALIN MESSENGER-RNA;
ADENYLYL-CYCLASE ACTIVITY; NUCLEUS-ACCUMBENS; RAT-BRAIN; OPIATE;
EXPRESSION; PET; SUFENTANIL; ALFENTANIL
AB Chronic cocaine exposure in both rodents and humans increases regional brain mu-opioid receptor (mOR) binding potential, suggesting that cocaine users might have an altered response to mOR agonists. We evaluated the response to IV carfentanil (a selective mOR agonist) in 23 cocaine users [mean (standard deviation) age 33.8 (4.0) years, 83% men] who underwent positron emission tomography (PET) scanning with [C-11]-carfentanil [44.7 (19.5) ng/kg] while housed on a closed research ward and 15 healthy non-drug-using controls [43.9 (14.2) years, 80% men] scanned [49.5 (12.6) ng/kg] as outpatients. Cocaine users had used for 8.7 (4.3) years and on 73 (22)% of days in the two weeks prior to PET scanning. Common adverse effects associated with mOR agonists (nausea, dizziness, headache, vomiting, itchiness) were assessed by self-report (five-point Likert scales) during and for 90 minutes after the scans. Cocaine users were significantly less likely than controls to report any symptom (30.4% versus 60%) and had fewer total symptoms [0.43 (0.73) versus 1.1 (1.0)] during scans, even after statistically controlling for age and carfentanil dose. These differences were also present after the scans and at repeat scans performed after about one week or 12 weeks of monitored cocaine abstinence. In a larger group of cocaine users and separate controls, there was no significant group difference in carfentanil half-life, suggesting that the observed difference was pharmacodynamically, rather than pharmacokinetically, based. These findings suggest that cocaine users are less responsive than healthy controls to mOR agonist adverse effects despite having increased regional brain mOR binding potential.
C1 [Minkowski, Carolynne P.; Epstein, David; Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Gorelick, DA (reprint author), 251 Bayview Blvd,200, Baltimore, MD 21224 USA.
EM dgorelic@intra.nida.nih.gov
FU NIH [DA-09479, DA-11774, DA-12274]; IRP, National Institutes of Health,
NIDA
FX Supported by the IRP, National Institutes of Health, NIDA and NIH grants
DA-09479, DA-11774 & DA-12274 (to Dr Frost). We thank Dr John Hilton for
assay of plasma carfentanil concentrations.
NR 31
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U1 2
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JAN
PY 2012
VL 17
IS 1
BP 149
EP 155
DI 10.1111/j.1369-1600.2010.00256.x
PG 7
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 865HW
UT WOS:000298303000013
PM 21054687
ER
PT J
AU Boettcher, E
Csako, G
Pucino, F
Wesley, R
Loomba, R
AF Boettcher, E.
Csako, G.
Pucino, F.
Wesley, R.
Loomba, R.
TI Meta-analysis: pioglitazone improves liver histology and fibrosis in
patients with non-alcoholic steatohepatitis
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID INSULIN-SENSITIZING AGENTS; PLACEBO-CONTROLLED TRIAL; CRYPTOGENIC
CIRRHOSIS; DIABETES-MELLITUS; NATURAL-HISTORY; VITAMIN-E; DISEASE;
ROSIGLITAZONE; TROGLITAZONE; RESISTANCE
AB Background Thiazolidinediones (TZDs) have been used in the treatment of non-alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically. Aim To conduct a meta-analysis of randomised, placebo-controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH. Methods Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters. Results Four good quality RPCTs derived from three continents were included. The meta-analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.333.36), 2.58 (95% CI, 1.683.97) and 3.39 (95% CI, 2.195.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.0314.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.022.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment. Conclusions Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo-controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis.
C1 [Boettcher, E.; Loomba, R.] Univ Calif San Diego, Div Gastroenterol, Dept Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Loomba, R.] Univ Calif San Diego, Div Epidemiol, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Csako, G.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pucino, F.] NIDDK, Ctr Clin, NIH, Bethesda, MD USA.
[Wesley, R.] NIH, Hosp Epidemiol Div, Ctr Clin, Bethesda, MD 20892 USA.
RP Loomba, R (reprint author), Univ Calif San Diego, Div Gastroenterol, Dept Med, Dept Family & Prevent Med, 9500 Gilman Dr,MC 0063, La Jolla, CA 92093 USA.
EM roloomba@ucsd.edu
FU AGA-Foundation; Daiichi Sankyo Inc; National Institutes of Health
[RO1AG28507, R37AG007181, RO1DK31801]; American Gastroenterological
Association (AGA) Foundation - Sucampo - ASP Designated Research; T.
Franklin Williams Scholarship Award; Atlantic Philanthropies, Inc; John
A. Hartford Foundation; Association of Specialty Professors; American
Gastroenterological Association; UCSD Digestive Diseases Research
Development Center, U.S. PHS [DK080506]
FX Declaration of personal interests: Rohit Loomba has served as a
consultant for Corgenix Inc and an advisory board member for Gilead Inc
and Daiichi Sankyo Inc, and has received research funding from the
AGA-Foundation, Daiichi Sankyo Inc and National Institutes of Health.
Declaration of funding interests: This work is supported in part by the
American Gastroenterological Association (AGA) Foundation - Sucampo -
ASP Designated Research Award in Geriatric Gastroenterology and by a T.
Franklin Williams Scholarship Award. Funding provided by: Atlantic
Philanthropies, Inc, the John A. Hartford Foundation, the Association of
Specialty Professors, and the American Gastroenterological Association
to Rohit Loomba, MD, MHSc. This research was funded in part with the
support of the UCSD Digestive Diseases Research Development Center, U.S.
PHS grant #DK080506. This work was supported in part by the National
Institute of Health grants RO1AG28507, R37AG007181, and RO1DK31801 to
Elizabeth Barrett-Connor, MD.
NR 34
TC 81
Z9 85
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JAN
PY 2012
VL 35
IS 1
BP 66
EP 75
DI 10.1111/j.1365-2036.2011.04912.x
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 860BX
UT WOS:000297922600007
PM 22050199
ER
PT J
AU Lamas, GA
Goertz, C
Boineau, R
Mark, DB
Rozema, T
Nahin, RL
Drisko, JA
Lee, KL
AF Lamas, Gervasio A.
Goertz, Christine
Boineau, Robin
Mark, Daniel B.
Rozema, Theodore
Nahin, Richard L.
Drisko, Jeanne A.
Lee, Kerry L.
TI Design of the Trial to Assess Chelation Therapy (TACT)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; INTERMITTENT
CLAUDICATION; ANTIOXIDANT VITAMINS; CLINICAL-TRIALS; DOUBLE-BLIND;
PREVENTION; EDTA; QUESTIONNAIRE; METAANALYSIS
AB TACT is an National Institutes of Health-sponsored, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial testing the benefits and risks of 40 infusions of a multicomponent disodium EDTA chelation solution compared with placebo and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow up 1,708 patients for an average of approximately 4 years. The primary end point is a composite of all-cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900-patient substudy will examine qualityof- life outcomes. The trial is designed to have N85% power to detect a 25% relative reduction in the primary end point for each treatment factor. Enrollment began in September 2003 and was completed in October 2010. (Am Heart J 2012; 163: 7-12.)
C1 [Lamas, Gervasio A.] Mt Sinai Med Ctr, Miami Beach, FL 33140 USA.
[Goertz, Christine] Palmer Ctr Chiropract Res, Davenport, IA USA.
[Boineau, Robin] NHLBI, Bethesda, MD 20892 USA.
[Mark, Daniel B.; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA.
[Rozema, Theodore] Biogenesis Med Ctr, Landrum, SC, Brazil.
[Nahin, Richard L.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Drisko, Jeanne A.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
RP Lamas, GA (reprint author), Mt Sinai Med Ctr, 4300 Alton Rd, Miami Beach, FL 33140 USA.
EM gervasio.lamas@msmc.com
OI Nahin, Richard/0000-0002-3682-4816; Mark, Daniel/0000-0001-6340-8087
FU Florida Heart Research Foundation
FX The authors wish to acknowledge the valuable contributions of the
following individuals: Ronald Hoffman, MD and Charles Hennekens, MD,
DrPh, for protocol design; the CCC project directors (Ana Mon, MPH;
Jacqueline Arciniega, MPH; Jaime Zimmerman, MPH; and Danielle Hollar,
PhD); the CCC trial managers (Esteban Escolar, MD; Faisal Shamshad, MD;
Pablo Guala, MD; Kayvan Amini, DO; Steven Hussein, MD; Alan Ackermann,
DO); the project managers at the DCC (Sandra Tourt-Uhlig, RN, MSN; Joyce
Good, RN, CCRC; Lindsay Lambe, BA, CNMT; Wanda Parker, RN, MSN; Nancy
Clapp-Channing, BSN, MPH; Diane Minshall-Liu, CCRP); the NHLBI team
members (Yves Rosenberg, MD; Mario Stylaniou, PhD; and Erin Iturriaga,
RN, BS) and DSMB members (Howard Hodis, MD-Chair; Stephen Buckley,
PharmD; Barry Davis, MD, PhD; Theodore Ganiats, MD; Robert Nash, MD; D.
GeorgeWyse, MD, PhD; and Gail Geller, ScD, MHS); the project directors
at Omnicomm Systems (Chris Droz, Brandon Diaz) and the central pharmacy
team (Eric M. Alvarez, PharmD; Juan Mora RPh; Marcia Perez); the NCCAM
Office of Communication and Outreach (Alyssa Cotler, MPH); the NHLBI
Office of Communications (Susan Dambrauskas, NHLBI press team leader);
and the Florida Heart Research Foundation for funding the pilot study.
NR 32
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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 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2012
VL 163
IS 1
BP 7
EP 12
DI 10.1016/j.ahj.2011.10.002
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 863HI
UT WOS:000298153000004
PM 22172430
ER
PT J
AU Flynn, KE
Lin, L
Moe, GW
Howlett, JG
Fine, LJ
Spertus, JA
McConnell, TR
Pina, IL
Weinfurt, KP
AF Flynn, Kathryn E.
Lin, Li
Moe, Gordon W.
Howlett, Jonathan G.
Fine, Lawrence J.
Spertus, John A.
McConnell, Timothy R.
Pina, Ileana L.
Weinfurt, Kevin P.
CA HF-ACTION Investigators
TI Relationships between changes in patient-reported health status and
functional capacity in outpatients with heart failure
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID QUALITY-OF-LIFE; CARDIAC RESYNCHRONIZATION; CONTROLLED-TRIAL; HF-ACTION;
OUTCOMES; QUESTIONNAIRE; MORBIDITY; MORTALITY
AB Background Heart failure trials use a variety of measures of functional capacity and quality of life. Lack of formal assessments of the relationships between changes in multiple aspects of patient-reported health status and measures of functional capacity over time limits the ability to compare results across studies.
Methods Using data from HF-ACTION (N = 2331), we used the Pearson correlation coefficients and predicted change scores from linear mixed-effects modeling to demonstrate the associations between changes in patient-reported health status measured with the EQ-5D visual analog scale and the Kansas City Cardiomyopathy Questionnaire (KCCQ) and changes in peak VO(2) and 6-minute walk distance at 3 and 12 months. We examined a 5-point change in KCCQ within individuals to provide a framework for interpreting changes in these measures.
Results After adjustment for baseline characteristics, correlations between changes in the visual analog scale and changes in peak VO2 and 6-minute walk distance ranged from 0.13 to 0.28, and correlations between changes in the KCCQ overall and subscale scores and changes in peak VO(2) and 6-minute walk distance ranged from 0.18 to 0.34. A 5-point change in KCCQ was associated with a 2.50-mL kg(-1) min(-1) change in peak VO(2) (95% CI 2.21-2.86) and a 112-m change in 6-minute walk distance (95% CI 96-134).
Conclusions Changes in patient-reported health status are not highly correlated with changes in functional capacity. Our findings generally support the current practice of considering a 5-point change in the KCCQ within individuals to be clinically meaningful. (Am Heart J 2012;163:88-94.e3.)
C1 [Flynn, Kathryn E.; Lin, Li; Weinfurt, Kevin P.] Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC 27715 USA.
[Flynn, Kathryn E.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27715 USA.
[Moe, Gordon W.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Howlett, Jonathan G.] Univ Calgary, Calgary, AB, Canada.
[Fine, Lawrence J.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA.
[Spertus, John A.] Univ Missouri, Kansas City, KS USA.
[McConnell, Timothy R.] Bloomsburg Univ, Dept Exercise Sci, Bloomsburg, PA USA.
[Pina, Ileana L.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA.
RP Flynn, KE (reprint author), Duke Univ, Duke Clin Res Inst, Sch Med, POB 17969, Durham, NC 27715 USA.
EM kathryn.flynn@duke.edu
RI Flynn, Kathryn/M-5346-2013
OI Flynn, Kathryn/0000-0002-4427-3583
FU National Heart, Lung, and Blood Institute [5U01HL063747, 5U01HL066461,
5U01HL068973, 5U01HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494,
5U01HL064257, 5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491,
5U01HL064264]; National Institute on Aging [R37AG018915, P60AG010484]
FX HF-ACTION was funded by grants 5U01HL063747, 5U01HL066461, 5U01HL068973,
5U01HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494, 5U01HL064257,
5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491, and 5U01HL064264
from the National Heart, Lung, and Blood Institute and grants
R37AG018915 and P60AG010484 from the National Institute on Aging.
NR 28
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U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2012
VL 163
IS 1
BP 88
EP U120
DI 10.1016/j.ahj.2011.09.027
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 863HI
UT WOS:000298153000015
PM 22172441
ER
PT J
AU Rienstra, M
Sun, JX
Lubitz, SA
Frankel, DS
Vasan, RS
Levy, D
Magnani, JW
Sullivan, LM
Meigs, JB
Ellinor, PT
Benjamin, EJ
AF Rienstra, Michiel
Sun, Jenny X.
Lubitz, Steven A.
Frankel, David S.
Vasan, Ramachandran S.
Levy, Daniel
Magnani, Jared W.
Sullivan, Lisa M.
Meigs, James B.
Ellinor, Patrick T.
Benjamin, Emelia J.
TI Plasma resistin, adiponectin, and risk of incident atrial fibrillation:
The Framingham Offspring Study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CONGESTIVE-HEART-FAILURE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION;
OBESITY; ONSET; PIOGLITAZONE; HYPERTENSION; INFLAMMATION; INDIVIDUALS;
POPULATION
AB Background We sought to investigate whether higher concentrations of resistin and lower concentrations of adiponectin relate to incident atrial fibrillation (AF) and whether this association is mediated by AF risk factors and inflammation. Resistin and adiponectin are adipokines that have been associated with multiple known risk factors for AF including diabetes, obesity, inflammation, and heart failure.
Methods We studied the relations between circulating concentrations of both adipokines and incident AF in participants of the Framingham Offspring Study.
Results Participants (n = 2,487) had a mean age of 61 +/- 10 years, and 54% were women. During a mean follow-up of 7.6 +/- 2.0 years, 206 (8.3%) individuals (96 women) developed incident AF. Plasma resistin concentration was significantly associated with incident AF (multivariable-adjusted hazard ratio [HR] 1.17 per SD [0.41 ng/mL] of natural logarithmically transformed resistin, 95% CI 1.02-1.34, P =.028). The resistin-AF association was attenuated after further adjustment for C-reactive protein (HR per SD increase resistin 1.14, 95% CI 0.99-1.31, P =.073). Adiponectin concentrations were not significantly associated with incident AF (multivariable-adjusted HR of 0.95 per SD [0.62 mu g/mL] of logarithmically transformed adiponectin, 95% CI 0.81-1.10, P =.478).
Conclusion In our community-based longitudinal study, higher mean concentrations of resistin were associated with incident AF, but the relation was attenuated by adjustment for C-reactive protein. We did not detect a statistically significant association between adiponectin and incident AF. Additional studies are needed to clarify the potential role of adipokines in AF and mechanisms linking adiposity to AF. (Am Heart J 2012; 163: 119-124. e1.)
C1 [Rienstra, Michiel; Vasan, Ramachandran S.; Levy, Daniel; Magnani, Jared W.; Meigs, James B.; Ellinor, Patrick T.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rienstra, Michiel; Vasan, Ramachandran S.; Levy, Daniel; Magnani, Jared W.; Meigs, James B.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Sun, Jenny X.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA.
[Frankel, David S.] Hosp Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Framingham, MA 01702 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Framingham, MA 01702 USA.
[Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Framingham, MA 01702 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med,Dept Med, Boston, MA USA.
RP Benjamin, EJ (reprint author), Boston Univ, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM emelia@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan,
Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336;
Rienstra, Michiel/0000-0002-2581-070X
FU National Heart, Lung, and Blood Institute; NHLBI/NIH [N01-HC-25195];
Boston University School of Medicine; Netherlands Organization for
Scientific Research [825.09.020]; National Institutes of Health
[1R01HL092577, 1RC1HL101056, 1R01HL102214, R01AG028321, 6R01-NS17950,
5R21DA027021, 5RO1HL104156, 1K24HL105780, R01-DK-080739]; American Heart
Association [09FTF2190028]; Evans Center for Interdisciplinary
Biomedical Research ARC on "Atrial Fibrillation" at Boston University
FX The Framingham Heart Study is supported by National Heart, Lung, and
Blood Institute; Framingham Heart Study (NHLBI/NIH contract
N01-HC-25195); and the Boston University School of Medicine. Dr Rienstra
is supported by a grant from the Netherlands Organization for Scientific
Research (Rubicon grant 825.09.020). This work was supported by grants
from the National Institutes of Health to Drs Benjamin and Ellinor
(1R01HL092577); Dr Benjamin (1RC1HL101056, 1R01HL102214, R01AG028321;
and support via 6R01-NS17950) and Dr Ellinor (5R21DA027021,
5RO1HL104156, 1K24HL105780); and Dr Vasan (R01-DK-080739). Dr Magnani is
supported by American Heart Association Award 09FTF2190028. This work
was partially supported by the Evans Center for Interdisciplinary
Biomedical Research ARC on "Atrial Fibrillation" at Boston University
(http://www.bumc.bu.edu/evanscenteribr/).
NR 37
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U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2012
VL 163
IS 1
BP 119
EP U151
DI 10.1016/j.ahj.2011.09.029
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 863HI
UT WOS:000298153000019
PM 22172445
ER
PT J
AU Daniel, CR
Cross, AJ
Graubard, BI
Park, Y
Ward, MH
Rothman, N
Hollenbeck, AR
Chow, WH
Sinha, R
AF Daniel, Carrie R.
Cross, Amanda J.
Graubard, Barry I.
Park, Yikyung
Ward, Mary H.
Rothman, Nathaniel
Hollenbeck, Albert R.
Chow, Wong-Ho
Sinha, Rashmi
TI Large prospective investigation of meat intake, related mutagens, and
risk of renal cell carcinoma
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION;
RETIRED-PERSONS DIET; KIDNEY CANCER; RED MEAT; HETEROCYCLIC AMINES;
NATIONAL-INSTITUTES; N-NITROSATION; CONSUMPTION; COOKING
AB Background: The evidence for meat intake and renal cell carcinoma (RCC) risk is inconsistent. Mutagens related to meat cooking and processing, and variation by RCC subtype may be important to consider.
Objective: In a large US cohort, we prospectively investigated intake of meat and meat-related compounds in relation to risk of RCC, as well as clear cell and papillary RCC histologic subtypes.
Design: Study participants (492,186) completed a detailed dietary assessment linked to a database of heme iron, heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAHs), nitrate, and nitrite concentrations in cooked and processed meats. Over 9 (mean) y of follow-up, we identified 1814 cases of RCC (498 clear cell and 115 papillary adenocarcinomas). HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression.
Results: Red meat intake [62.7 g (quintile 5) compared with 9.8 g (quintile 1) per 1000 kcal (median)] was associated with a tendency toward an increased risk of RCC [HR: 1.19; 95% CI: 1.01, 1.40; P-trend = 0.06] and a 2-fold increased risk of papillary RCC [P-trend = 0.002]. Intakes of benzo(a) pyrene (BaP), a marker of PAHs, and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), an HCA, were associated with a significant 20-30% elevated risk of RCC and a 2-fold increased risk of papillary RCC. No associations were observed for the clear cell subtype.
Conclusions: Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP. Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant. This study is registered at clinicaltrials.gov as NCT00340015. Am J Clin Nutr 2012;95:155-62.
C1 [Daniel, Carrie R.; Cross, Amanda J.; Graubard, Barry I.; Park, Yikyung; Ward, Mary H.; Rothman, Nathaniel; Chow, Wong-Ho; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Daniel, CR (reprint author), 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA.
EM carrie.dan-iel@nih.hhs.gov
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, NIH; Florida Department of Health (FDOH)
FX Supported by the Intramural Research Program of the National Cancer
Institute, NIH.; Cancer incidence data from the Atlanta metropolitan
area were collected by the Georgia Center for Cancer Statistics,
Department of Epidemiology, Rollins School of Public Health, Emory
University. Cancer incidence data from California were collected by the
California Department of Health Services, Cancer Surveillance Section.
Cancer incidence data from the Detroit metropolitan area were collected
by the Michigan Cancer Surveillance Program, Community Health
Administration, State of Michigan. The Florida cancer incidence data
used in this report were collected by the Florida Cancer Data System
(FCDC) under contract with the Florida Department of Health (FDOH).
Cancer incidence data from Louisiana were collected by the Louisiana
Tumor Registry, Louisiana State University Medical Center in New
Orleans. Cancer incidence data from New Jersey were collected by the New
Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey
State Department of Health and Senior Services. Cancer incidence data
from North Carolina were collected by the North Carolina Central Cancer
Registry. Cancer incidence data from Pennsylvania were supplied by the
Di vision of Health Statistics and Research, Pennsylvania Department of
Health, Harrisburg, PA. The Pennsylvania Department of Health
specifically disclaims responsibility for any analyses, interpretations
or conclusions. Cancer incidence data from Arizona were collected by the
Arizona Cancer Registry, Division of Public Health Services, Arizona
Department of Health Services. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services.
NR 43
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Z9 17
U1 0
U2 11
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 JAN
PY 2012
VL 95
IS 1
BP 155
EP 162
DI 10.3945/ajcn.111.019364
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 866SF
UT WOS:000298402100021
PM 22170360
ER
PT J
AU Beydoun, MA
Ding, EL
Beydoun, HA
Tanaka, T
Ferrucci, L
Zonderman, AB
AF Beydoun, May A.
Ding, Eric L.
Beydoun, Hind A.
Tanaka, Toshiko
Ferrucci, Luigi
Zonderman, Alan B.
TI Vitamin D receptor and megalin gene polymorphisms and their associations
with longitudinal cognitive change in US adults
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NERVE GROWTH-FACTOR; D-BINDING PROTEIN; ALZHEIMERS-DISEASE;
1,25-DIHYDROXYVITAMIN D-3; D DEFICIENCY; AMYLOID-BETA; MEDIATED
ENDOCYTOSIS; HIPPOCAMPAL-NEURONS; APOLIPOPROTEIN J; CELLULAR UPTAKE
AB Background: Vitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cognitive change remains unclear.
Objective: The associations of single nucleotide polymorphisms (SNPs) for VDR [rs11568820 (CdX-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI: G/A)], and Megalin (rs3755166: G/A; rs2075252: C/T; rs4668123:C/T) genes with longitudinal cognitive performance changes were examined.
Design: Data from 702 non-Hispanic white participants in the Baltimore Longitudinal Study of Aging were used. Longitudinal annual rates of cognitive change (LARCCs) between age 50 y and the individual mean follow-up age were predicted with linear mixed models by using all cognitive score time points (prediction I) or time points before dementia onset (prediction II). Latent class, haplotype, and ordinary least squares (OLS) regression analyses were conducted.
Results: Among key findings, in OLS models with SNP latent classes as predictors for LARCCs, Megalin(2) [rs3755166(-)/rs2075252(TT)/rs4668123(T-)] compared with Megalin(1) [rs3755166(-)/rs2075252 (CC)/rs4668123(-)] was associated with greater decline among men for verbal memory (prediction II). Significant sex differences were also found for SNP haplotype (SNPHAP). In women, VDR(1) [BsmI (G-)/ApaI(C-)/TaqI(A-); baT] was linked to a greater decline in category fluency (prediction I: beta = -0.031, P = 0.012). The Megalin1 SNPHAP (GCC) was related to greater decline among women for verbal memory, immediate recall [California Verbal Learning Test (CVLT), List A; prediction II: beta = -0.043, P = 0.006) but to slower decline among men for delayed recall (CVLT-DR: beta > 0, P < 0.0125; both predictions). In women, the Megalin2 SNPHAP (ACC) was associated with slower decline in category fluency (prediction II: beta = +0.026, P = 0.005). Another finding was that Megalin SNP rs3755166: G/A was associated with greater decline in global cognition in both sexes combined and in verbal memory in men.
Conclusion: Sex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults. Am J Clin Nutr 2012;95:163-78.
C1 [Beydoun, May A.] NIA, NIH Biomed Res Ctr, IRP, NIH, Baltimore, MD 21224 USA.
[Ding, Eric L.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
RP Beydoun, MA (reprint author), NIA, NIH Biomed Res Ctr, IRP, NIH, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Ding, Eric/0000-0002-5881-8097; Zonderman, Alan B/0000-0002-6523-4778
FU NIH, National Institute on Aging
FX Supported entirely by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 78
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U1 1
U2 4
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 JAN
PY 2012
VL 95
IS 1
BP 163
EP 178
DI 10.3945/ajcn.111.017137
PG 16
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 866SF
UT WOS:000298402100022
PM 22170372
ER
PT J
AU Edwards, TL
Edwards, DRV
Villegas, R
Cohen, SS
Buchowski, MS
Fowke, JH
Schlundt, D
Long, JR
Cai, QY
Zheng, W
Shu, XO
Hargreaves, MK
Jeffrey, S
Williams, SM
Signorello, LB
Blot, WJ
Matthews, CE
AF Edwards, Todd L.
Edwards, Digna R. Velez
Villegas, Raquel
Cohen, Sarah S.
Buchowski, Maciej S.
Fowke, Jay H.
Schlundt, David
Long, Ji Rong
Cai, Qiuyin
Zheng, Wei
Shu, Xiao-Ou
Hargreaves, Margaret K.
Jeffrey, Smith
Williams, Scott M.
Signorello, Lisa B.
Blot, William J.
Matthews, Charles E.
TI HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and Obesity in a Cohort of
Caucasians and African Americans: An Evaluation of Gene-Environment
Interactions and Candidate Genes
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE African continental ancestry group; body mass index; European
continental ancestry group; genetics; molecular epidemiology; obesity
ID ACTIVATED-RECEPTOR-GAMMA; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; FOOD
FREQUENCY QUESTIONNAIRE; SOUTHERN COMMUNITY COHORT; TYPE-2
DIABETES-MELLITUS; 5-HT1B RECEPTOR; GLY482SER POLYMORPHISM;
INSULIN-RESISTANCE; MAJOR DEPRESSION
AB The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height(m)(2)) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002-2009) for associations with BMI and gene x environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (beta = -0.04, 95% confidence interval: -0.06, -0.02; P = 5.76 x 10(-5)) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians.
C1 [Edwards, Todd L.; Villegas, Raquel; Buchowski, Maciej S.; Fowke, Jay H.; Long, Ji Rong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou; Jeffrey, Smith; Signorello, Lisa B.; Blot, William J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37203 USA.
[Edwards, Todd L.; Villegas, Raquel; Fowke, Jay H.; Long, Ji Rong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN 37203 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
[Cohen, Sarah S.; Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Buchowski, Maciej S.; Fowke, Jay H.; Schlundt, David; Long, Ji Rong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou; Hargreaves, Margaret K.; Jeffrey, Smith; Signorello, Lisa B.; Blot, William J.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
[Hargreaves, Margaret K.] Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA.
[Schlundt, David; Jeffrey, Smith] Vet Affairs Tennessee Valley Healthcare Syst, Med Res Serv, Nashville, TN USA.
[Williams, Scott M.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37203 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Edwards, TL (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA.
EM todd.l.edwards@vanderbilt.edu
RI Williams, Scott/B-9491-2012; Edwards, Todd/B-9750-2012; Velez Edwards,
Digna/C-1090-2012; Buchowski, Maciej/A-2683-2008; Smith,
Jeff/C-3484-2012; matthews, Charles/E-8073-2015
OI Buchowski, Maciej/0000-0002-0566-1743; matthews,
Charles/0000-0001-8037-3103
FU Susan G. Komen for the Cure Foundation [OP05-0927-DR1]; National Cancer
Institute [R01 CA092447]; Vanderbilt-Ingram Cancer Center [P30 CA68485];
Vanderbilt Clinical and Translational Research Scholar award
[5KL2RR024975-04]; Building Interdisciplinary Research Careers in
Women's Health career development program [K12HD4383]
FX This project was funded in part by grant OP05-0927-DR1 from the Susan G.
Komen for the Cure Foundation. The Southern Community Cohort Study is
funded by grant R01 CA092447 from the National Cancer Institute. Sample
preparation was conducted by the Survey and Biospecimen Shared Resource,
which is supported in part by the Vanderbilt-Ingram Cancer Center (grant
P30 CA68485). Dr. Todd L. Edwards also received support through
Vanderbilt Clinical and Translational Research Scholar award
5KL2RR024975-04. Additional funds were provided by the Building
Interdisciplinary Research Careers in Women's Health career development
program (grant K12HD4383) for Dr. Digna Velez Edwards' salary.
NR 67
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U1 1
U2 14
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 JAN 1
PY 2012
VL 175
IS 1
BP 11
EP 21
DI 10.1093/aje/kwr272
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 866MF
UT WOS:000298384300002
PM 22106445
ER
PT J
AU Dodd, KW
Midthune, D
Kipnis, V
AF Dodd, Kevin W.
Midthune, Douglas
Kipnis, Victor
TI RE: "APPLICATION OF A REPEAT-MEASURE BIOMARKER MEASUREMENT ERROR MODEL
TO 2 VALIDATION STUDIES: EXAMINATION OF THE EFFECT OF WITHIN-PERSON
VARIATION IN BIOMARKER MEASUREMENTS"
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID DOUBLY LABELED WATER; ENERGY-EXPENDITURE
C1 [Dodd, Kevin W.; Midthune, Douglas; Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Dodd, KW (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM doddk@mail.nih.gov
NR 10
TC 3
Z9 3
U1 0
U2 1
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 JAN 1
PY 2012
VL 175
IS 1
BP 84
EP 85
DI 10.1093/aje/kwr390
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 866MF
UT WOS:000298384300010
PM 22088499
ER
PT J
AU Kopp, JB
Winkler, CA
AF Kopp, Jeffrey B.
Winkler, Cheryl A.
TI Genetic Risk Prediction for CKD: A Journey of a Thousand Miles
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR RISK; SCORE; ASSOCIATION; CURVE;
MODEL
C1 [Kopp, Jeffrey B.; Winkler, Cheryl A.] NIH, Bethesda, MD 20892 USA.
RP Kopp, JB (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Intramural NIH HHS [Z01 DK043308-12]
NR 28
TC 0
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U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JAN
PY 2012
VL 59
IS 1
BP 4
EP 8
DI 10.1053/j.ajkd.2011.11.011
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 863HO
UT WOS:000298153600004
PM 22177444
ER
PT J
AU O'Seaghdha, CM
Yang, Q
Wu, HS
Hwang, SJ
Fox, CS
AF O'Seaghdha, Conall M.
Yang, Qiong
Wu, Hongsheng
Hwang, Shih-Jen
Fox, Caroline S.
TI Performance of a Genetic Risk Score for CKD Stage 3 in the General
Population
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; genetics; risk prediction
ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE;
GLOMERULAR-FILTRATION-RATE; DIABETIC-NEPHROPATHY; RENAL-INSUFFICIENCY;
UNITED-STATES; PREVALENCE; ADULTS; PREDICTION; FRAMINGHAM
AB Background: Recent genome-wide association studies have identified multiple genetic loci that increase the risk of chronic kidney disease (CKD) in the general population. We hypothesized that knowledge of these loci might permit improved CKD risk prediction beyond that provided by traditional phenotypic risk factors.
Study Design: Observational cohort study.
Setting & Participants: Participants who attended the 15th (1977-1979) and 24th (1995-1998) examination cycles of the original cohort or the 6th (1995-1998) and 8th cycles (2005-2008) of the offspring cohort of the Framingham Heart Study (n = 2,489).
Predictors: Single-nucleotide polymorphisms at 16 stage 3 CKD loci were genotyped and used to construct a genetic risk score. Standard clinical predictors of incident stage 3 CKD also were used.
Outcomes & Measurements: Incident stage 3 CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) at follow-up. Participants with baseline stage 3 CKD were excluded. Logistic regression was used to generate C statistics, which measured the power of the genetic risk score to discriminate risk of incident CKD stage 3 with and without traditional risk factors.
Results: There were 270 new stage 3 CKD cases during an average of 10.8 years of follow-up. Mean genetic risk score was 17.5 +/- 2.8 (SD) for those who developed stage 3 CKD and 17.3 +/- 2.6 for those who did not (P for genotype score difference = 0.2). The OR for stage 3 CKD was 1.06 (95% CI, 1.01-1.11; P = 0.03) per additional risk allele, adjusting for age and sex. In the age-and sex-adjusted model, the C statistic was 0.748 without the genotype score and 0.751 with the score (P difference = 0.3). The risk score was not statistically significant in a multivariable model adjusted for standard stage 3 CKD risk factors (P = 0.07).
Limitations: All participants were of European ancestry; the genotype score may not be valid in different ancestral groups.
Conclusions: A genetic score generated from 16 known CKD risk alleles did not predict new cases of stage 3 CKD in the community beyond knowledge of common clinical risk factors alone. Am J Kidney Dis. 59(1): 19-24. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Brigham & Womens Hosp, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Yang, Qiong; Wu, Hongsheng] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Wu, Hongsheng] Wentworth Inst Technol, Dept Comp Sci, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
RI Yang, Qiong/G-5438-2014
FU NHLBI's FHS [N01-HC-25195]
FX This research was conducted in part using data and resources from the
FHS of the National Heart, Lung, and Blood Institute (NHLBI) of the
National Institutes of Health and Boston University School of Medicine.
This work was partially supported by the NHLBI's FHS (Contract No.
N01-HC-25195). The sponsors had no role in the conduct or interpretation
of the study. The corresponding author had full access to all data in
the study and had final responsibility for the decision to submit for
publication.
NR 41
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U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JAN
PY 2012
VL 59
IS 1
BP 19
EP 24
DI 10.1053/j.ajkd.2011.08.030
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 863HO
UT WOS:000298153600008
PM 21995970
ER
PT J
AU Yin, F
Wilson, T
Della Fave, A
Larsen, M
Yoon, J
Nugusie, B
Freeland, H
Chow, RD
AF Yin, Fang
Wilson, Thomas
Della Fave, Albert
Larsen, Moira
Yoon, Jenni
Nugusie, Binyam
Freeland, Howard
Chow, Robert Dobbin
TI Inappropriate Use of D-Dimer Assay and Pulmonary CT Angiography in the
Evaluation of Suspected Acute Pulmonary Embolism
SO AMERICAN JOURNAL OF MEDICAL QUALITY
LA English
DT Article
DE D-dimer; CT angiography; pulmonary embolism; emergency department
ID SIMPLE CLINICAL-MODEL; COMPUTED-TOMOGRAPHY; PROBABILITY; MANAGEMENT;
THROMBOSIS; EXCLUSION; DIAGNOSIS; OUTCOMES
AB The authors question whether the d-dimer assay and pulmonary computed tomography angiography (CTA) are being used appropriately to evaluate suspected acute pulmonary embolism (PE) at their hospital. To answer this question, a retrospective review was performed on all emergency department (ED) patients who underwent d-dimer assay and/or CTA from August 15, 2008, to August 14, 2009. The authors' algorithm for diagnosing PE requires that patients with low or intermediate probability of acute PE undergo a d-dimer assay, followed by CTA if the d-dimer is positive. Patients with high probability of PE should have CTA performed without a d-dimer assay. This result suggests that d-dimer assay and CTA are used inappropriately to evaluate patients with suspected acute PE in our ED. The low threshold for initiating an evaluation for PE decreases the prevalence of PE in this population.
C1 [Yin, Fang; Wilson, Thomas; Della Fave, Albert; Larsen, Moira; Yoon, Jenni; Nugusie, Binyam; Freeland, Howard; Chow, Robert Dobbin] Good Samaritan Hosp Maryland, Baltimore, MD USA.
RP Yin, F (reprint author), NHLBI, Hematol Branch, Bldg 10,CRC Room 4E-5140,10 Ctr Dr,MSC 1475, Bethesda, MD 21892 USA.
EM fang.yin@nih.gov
NR 19
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Z9 10
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1062-8606
J9 AM J MED QUAL
JI Am. J. Med. Qual.
PD JAN-FEB
PY 2012
VL 27
IS 1
BP 74
EP 79
DI 10.1177/1062860611407907
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 870FX
UT WOS:000298655700010
PM 21666066
ER
PT J
AU Ananth, CV
Wilcox, AJ
Gyamfi-Bannerman, C
AF Ananth, Cande V.
Wilcox, Allen J.
Gyamfi-Bannerman, Cynthia
TI Obstetrical interventions among nulliparous women in the United States,
2005-07
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Ananth, Cande V.; Gyamfi-Bannerman, Cynthia] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY USA.
[Wilcox, Allen J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
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U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 646
BP S289
EP S289
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900644
ER
PT J
AU Bailit, JL
AF Bailit, Jennifer L.
TI Use of maternal and neonatal outcomes to measure quality of care: is
hospital performance consistent across outcomes?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Bailit, Jennifer L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
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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
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 30
BP S20
EP S21
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900031
ER
PT J
AU Berggren, E
AF Berggren, Erica
TI The NICHD-MFMU GDM study: differences in perinatal outcomes between
Hispanic women and Non-Hispanic White women with and without gestational
diabetes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Berggren, Erica] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA.
NR 0
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U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 556
BP S252
EP S253
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900554
ER
PT J
AU Bousleiman, S
AF Bousleiman, Sabine
TI Translating research into practice in obstetrics
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Bousleiman, Sabine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 635
BP S284
EP S285
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900633
ER
PT J
AU Bousleiman, S
AF Bousleiman, Sabine
TI Maternal risk factors and small for gestational age neonates
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Bousleiman, Sabine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 634
BP S284
EP S284
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900632
ER
PT J
AU Chiossi, G
AF Chiossi, Giuseppe
TI Timing of delivery and adverse outcomes in term singleton repeat
cesarean deliveries (CD)
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Chiossi, Giuseppe] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 38
BP S26
EP S26
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900039
ER
PT J
AU Cho, HJ
Kim, YM
Jeon, GH
Kim, JY
Kim, CJ
Romero, R
AF Cho, Hyun Jin
Kim, Yeon Mee
Jeon, Gyun-Ho
Kim, Ji Yeon
Kim, Chong Jai
Romero, Roberto
TI CD36 expression in trophoblasts: implications for preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Cho, Hyun Jin; Kim, Yeon Mee; Jeon, Gyun-Ho; Kim, Ji Yeon] Inje Univ, Haeundae Paik Hosp, Pusan, South Korea.
[Kim, Chong Jai; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 807
BP S355
EP S355
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889901073
ER
PT J
AU Fuchs, KM
D'Alton, M
AF Fuchs, Karin M.
D'Alton, Mary
TI Can sonographer education and image review standardize image acquisition
and caliper placement in 2D ultrasounds? Experience from the NICHD Fetal
Growth Study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Fuchs, Karin M.; D'Alton, Mary] NICHHD, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 23
BP S15
EP S16
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900024
ER
PT J
AU Gilbert, SA
AF Gilbert, Sharon A.
TI The MFMU Cesarean Registry: cost-effectiveness of a trial of labor
compared with an elective repeat cesarean delivery after a previous
cesarean in a minimally biased cohort
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Gilbert, Sharon A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 681
BP S303
EP S303
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900678
ER
PT J
AU Gilbert, SA
AF Gilbert, Sharon A.
TI The MFMU cesarean registry: propensity score analysis for bias reduction
in comparing elective repeat cesarean delivery with trial of labor after
a previous cesarean
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Gilbert, Sharon A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 29
BP S20
EP S20
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900030
ER
PT J
AU Grobman, W
AF Grobman, William
TI Randomized controlled trial of progesterone treatment for preterm birth
prevention in nulliparous women with cervical length less than 30 mm
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Maternal Fetal Units Network, Bethesda, MD USA.
NR 0
TC 10
Z9 10
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 838
BP S367
EP S367
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889901104
ER
PT J
AU Grobman, W
AF Grobman, William
TI Does risk adjustment for patient characteristics affect assessment of
hospital quality performance?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Maternal Fetal Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 641
BP S287
EP S287
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900639
ER
PT J
AU Grobman, W
AF Grobman, William
TI The development of risk-adjusted outcomes to be used as quality
indicators for obstetric care
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Maternal Fetal Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 6
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 640
BP S286
EP S287
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900638
ER
PT J
AU Grobman, W
AF Grobman, William
TI Is an individualized growth standard better than a population-based
standard at predicting cerebral palsy or death among SGA infants?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Maternal Fetal Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 536
BP S242
EP S242
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900534
ER
PT J
AU Grobman, W
AF Grobman, William
TI Can differences in obstetric outcomes be explained by differences in the
care provided?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Grobman, William] Natl Inst Hlth & Human Dev, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 6
BP S4
EP S4
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900007
ER
PT J
AU Horowitz, K
Incerti, M
Roberson, R
Abebe, D
Toso, L
Caballero, M
Spong, CY
AF Horowitz, Kari
Incerti, Maddalena
Roberson, Robin
Abebe, Daniel
Toso, Laura
Caballero, Madeline
Spong, Catherine Y.
TI Prenatal treatment prevents learning deficit in down syndrome model
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Horowitz, Kari] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Incerti, Maddalena] Univ Milano Bicocca, Monza, Italy.
[Roberson, Robin; Abebe, Daniel; Toso, Laura; Caballero, Madeline; Spong, Catherine Y.] UPDN DIR, NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 53
BP S35
EP S35
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900054
ER
PT J
AU Horton, A
AF Horton, Amanda
TI The effect of magnesium sulfate administration for neuroprotection on
latency in women with preterm premature rupture of membranes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Horton, Amanda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 456
BP S209
EP S209
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900455
ER
PT J
AU Jeon, GH
Cho, HJ
Kim, JY
Kim, CJ
Romero, R
Kim, YM
AF Jeon, Gyun-Ho
Cho, Hyun Jin
Kim, Ji Yeon
Kim, Chong Jai
Romero, Roberto
Kim, Yeon Mee
TI The expression of CD36 in preterm and term pregnancies
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Jeon, Gyun-Ho; Cho, Hyun Jin; Kim, Ji Yeon; Kim, Yeon Mee] Inje Univ, Haeundae Paik Hosp, Pusan, South Korea.
[Kim, Chong Jai; Romero, Roberto] NICHHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 117
BP S64
EP S65
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900118
ER
PT J
AU Johnson, M
AF Johnson, Mark
TI Risk factors for preterm delivery and uterine dehiscence following
prenatal surgery for myelomeningocele
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Johnson, Mark] NICHD, MOMSTrial Grp, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 427
BP S197
EP S198
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900426
ER
PT J
AU Laughon, SK
Hazrati, S
Bowers, K
Zhang, CL
Grewal, U
AF Laughon, S. Katherine
Hazrati, Sahel
Bowers, Katherine
Zhang, Cuilin
Grewal, Una
TI Increased neonatal respiratory Morbidity associated with gestational and
pregestational diabetes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Laughon, S. Katherine; Bowers, Katherine; Zhang, Cuilin; Grewal, Una] NICHD, NIH, Epidemiol Branch, Bethesda, MD USA.
[Hazrati, Sahel] George Mason Univ, Fairfax, VA 22030 USA.
RI Bowers, Katherine/N-5226-2015
NR 0
TC 7
Z9 7
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 75
BP S47
EP S47
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900076
ER
PT J
AU Lee, SM
Romero, R
Lee, YJ
Park, IS
Park, CW
Yoon, BH
AF Lee, Seung Mi
Romero, Roberto
Lee, You Jeong
Park, In Sook
Park, Chan-Wook
Yoon, Bo Hyun
TI Systemic inflammatory stimulation by microparticles derived from hypoxic
trophoblast in preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Lee, Seung Mi] Seoul Metropolitan Govt Seoul Natl Univ Boramae M, Seoul, South Korea.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
[Lee, You Jeong] Seoul Natl Univ Coll Med, Dept Pathol, Seoul, South Korea.
[Park, In Sook; Park, Chan-Wook] Seoul Natl Univ Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
RI Park, Chan-Wook/J-5498-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 798
BP S351
EP S351
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889901064
ER
PT J
AU Lee, SM
Romero, R
Park, JW
Kim, BJ
Park, CW
Park, JS
Jun, JK
Yoon, BH
AF Lee, Seung Mi
Romero, Roberto
Park, Jeong Woo
Kim, Byung Jae
Park, Chan-Wook
Park, Joong Shin
Jun, Jong Kwan
Yoon, Bo Hyun
TI Histologic chorioamnionitis is a risk factor for adverse neonatal
outcome in late preterm birth following preterm PROM
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Kim, Byung Jae] Seoul Metropolitan Govt Seoul Natl Univ Boramae M, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
[Park, Chan-Wook; Park, Joong Shin; Jun, Jong Kwan] Seoul Natl Univ Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Park, Jeong Woo] Seoul Natl Univ Coll Med, Deptartment Obstet & Gynecol, Seoul, South Korea.
RI Park, Chan-Wook/J-5498-2012; Jun, Jong Kwan/D-5776-2012
OI Jun, Jong Kwan/0000-0002-0242-1736
NR 0
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 524
BP S237
EP S237
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900522
ER
PT J
AU Lesko, J
Peaceman, A
AF Lesko, Jennifer
Peaceman, Alan
TI Pregnancy outcomes after bariatric surgery compared with body mass index
matched controls
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Lesko, Jennifer] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Peaceman, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth &Huma, Maternal Fetal Med Units, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 322
BP S152
EP S153
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900321
ER
PT J
AU Olson, G
AF Olson, Gayle
TI Fetal growth restriction is associated with decreased developmental
screening scores in childhood
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Olson, Gayle] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 409
BP S190
EP S191
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900408
ER
PT J
AU Olson, G
AF Olson, Gayle
TI The relationship of birth weight to body mass index and blood pressure
at ages 3-5 years
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Olson, Gayle] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 408
BP S190
EP S190
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900407
ER
PT J
AU Park, CW
Yoon, BH
Jun, JK
Park, JS
Kim, BJ
Romero, R
AF Park, Chan-Wook
Yoon, Bo Hyun
Jun, Jong Kwan
Park, Joong Shin
Kim, Byung Jae
Romero, Roberto
TI Approximately one-fifth of patients with preterm labor and intact
membranes and low amniotic fluid white blood cell counts have evidence
of intra-amniotic inflammation and are at risk for impending preterm
delivery when MMP-8 is used
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Park, Chan-Wook; Jun, Jong Kwan; Park, Joong Shin; Kim, Byung Jae] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
RI Park, Chan-Wook/J-5498-2012; Jun, Jong Kwan/D-5776-2012
OI Jun, Jong Kwan/0000-0002-0242-1736
NR 0
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 469
BP S214
EP S214
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900468
ER
PT J
AU Park, CW
Yoon, BH
Jun, JK
Park, JS
Kim, SM
Romero, R
AF Park, Chan-Wook
Yoon, Bo Hyun
Jun, Jong Kwan
Park, Joong Shin
Kim, Sun Min
Romero, Roberto
TI The intraamniotic and fetal inflammatory response is more intense in
preterm labor with intact membranes than in preterm PROM
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Park, Chan-Wook; Jun, Jong Kwan; Park, Joong Shin] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
RI Park, Chan-Wook/J-5498-2012; Jun, Jong Kwan/D-5776-2012
OI Jun, Jong Kwan/0000-0002-0242-1736
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 468
BP S214
EP S214
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900467
ER
PT J
AU Peaceman, A
AF Peaceman, Alan
TI Prediction of cerebral palsy (CP) or death among preterm infants who
survive the neonatal period
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Peaceman, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 451
BP S207
EP S207
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900450
ER
PT J
AU Pereira, L
Wilmarth, P
AF Pereira, Leonardo
Wilmarth, Phil
TI Prediction of preterm birth in twin gestations through analysis of
maternal plasma at 24-30 weeks gestation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Pereira, Leonardo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
[Wilmarth, Phil] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA.
NR 0
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 502
BP S227
EP S227
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900500
ER
PT J
AU Pinar, H
Dudley, D
AF Pinar, Hal
Dudley, Donald
CA SCRN Investigators
TI Gestational age effects on pathologic findings of stillbirth placentas:
evidence from a population-based study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Pinar, Hal] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA.
[Dudley, Donald] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet Gynecol, San Antonio, TX 78229 USA.
[SCRN Investigators] Eunice Kennedy Shriver NICHD, Pregnancy & Perinatol Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 107
BP S61
EP S62
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900108
ER
PT J
AU Pinar, H
Dudley, D
AF Pinar, Hal
Dudley, Donald
CA Stillbirth Collaborative Res Netwo
TI Histologic features of the placenta in stillbirth: results of a case
control study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Pinar, Hal] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA.
[Dudley, Donald] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet Gynecol, San Antonio, TX 78229 USA.
[Stillbirth Collaborative Res Netwo] Eunice Kennedy Shriver NICHD, Pregnancy & Perinatol Branch, Bethesda, MD USA.
RI Bukowski, Radek/B-6976-2013
NR 0
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 106
BP S61
EP S61
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900107
ER
PT J
AU Roberson, R
Kuddo, T
Caballero, M
Horowitz, K
Spong, CY
AF Roberson, Robin
Kuddo, Thea
Caballero, Madeline
Horowitz, Kari
Spong, Catherine Y.
TI Hippocampal and cerebellar BDNF levels in the Ts65Dn mouse model of Down
syndrome
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Roberson, Robin; Kuddo, Thea; Caballero, Madeline; Spong, Catherine Y.] NICHD, UPDN, DIR, NIH, Bethesda, MD USA.
[Horowitz, Kari] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 720
BP S320
EP S320
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900715
ER
PT J
AU Roberson, R
Kuddo, T
Horowitz, K
Caballero, M
Spong, CY
AF Roberson, Robin
Kuddo, Thea
Horowitz, Kari
Caballero, Madeline
Spong, Catherine Y.
TI Cytokine and chemokine alterations in down syndrome
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Roberson, Robin; Kuddo, Thea; Caballero, Madeline; Spong, Catherine Y.] UPDN, NICHD, NIH, DIR, Bethesda, MD USA.
[Horowitz, Kari] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 59
BP S37
EP S37
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900060
ER
PT J
AU Schuit, E
Stock, S
Rouse, D
Lim, AC
Rode, L
Norman, J
Nassar, A
Serra, V
Combs, CA
Rozenberg, P
Cetingoz, E
Briery, C
Thom, E
Caritis, S
Klein, K
Tabor, A
Awwad, J
Usta, I
Perales, A
Meseguer, J
Maurel, K
Garite, T
Cam, C
Karateke, A
Morrison, J
Magann, E
Groenwold, RHH
Moons, K
Kwee, A
Mol, BW
AF Schuit, E.
Stock, Sarah
Rouse, Dwight
Lim, A. C.
Rode, Line
Norman, Jane
Nassar, Anwar
Serra, Vicente
Combs, C. Andrew
Rozenberg, Patrick
Cetingoz, Elcin
Briery, Christian
Thom, Elizabeth
Caritis, Steve
Klein, Katharina
Tabor, Ann
Awwad, Johnny
Usta, Ihab
Perales, Alfredo
Meseguer, Juan
Maurel, Kimberly
Garite, Thomas
Cam, Cetin
Karateke, Ates
Morrison, John
Magann, Everett
Groenwold, Rolf H. H.
Moons, Karel
Kwee, Anneke
Mol, Ben Willem
TI Progestogen in twin pregnancies: an individual participant data
meta-analysis of randomized trials
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Schuit, E.; Groenwold, Rolf H. H.; Moons, Karel] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Rouse, Dwight] NICHD MFMU Network Twins Trial, Providence, RI USA.
[Norman, Jane] Univ Edinburgh, MRC Ctr Reprod Hlth, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
[Nassar, Anwar; Awwad, Johnny; Usta, Ihab] Lebanese Progestogen Trial, Lebanon, NH USA.
[Briery, Christian; Morrison, John; Magann, Everett] Mississippi Progestogen Trial, Mississippi State, MS USA.
[Thom, Elizabeth] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Caritis, Steve] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
RI Mol, Ben /I-4526-2012
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 472
BP S215
EP S216
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900471
ER
PT J
AU Sibai, B
Koch, M
Freire, S
Silva, JLPE
Rudge, MVC
Martins-Costa, S
Goco, N
Santos, CD
Cecatti, JG
Costa, R
Ramos, JG
Moss, N
Spinnato, J
AF Sibai, Baha
Koch, Matthew
Freire, Salvio
Pinto e Silva, Joao Luiz
Cunha Rudge, Marilza Vieira
Martins-Costa, Sergio
Goco, Norman
Santos, Cleide de Barros
Cecatti, Jose Guilherme
Costa, Roberto
Ramos, Jose Geraldo
Moss, Nancy
Spinnato, Joseph, II
TI Are adverse perinatal outcomes (APOs) in chronic hypertension (CHTN)
mostly related to superimposed preeclampsia (PE)?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Sibai, Baha] Univ Cincinnati, Cincinnati, OH USA.
[Koch, Matthew] RTI Int Stat & Epidemiol Div, Durham, NC USA.
[Freire, Salvio] Univ Fed Pernamucco, Recife, PE, Brazil.
[Cecatti, Jose Guilherme] Univ Estadual Campinas, Campinas, Brazil.
[Pinto e Silva, Joao Luiz; Cunha Rudge, Marilza Vieira; Costa, Roberto] Univ Estadual Paulista, Botucatu, SP, Brazil.
[Martins-Costa, Sergio] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.
[Goco, Norman] RTI Int Res Triangle Pk, Stat & Epidemiol Div, Durham, NC USA.
[Santos, Cleide de Barros] Univ Fed Pernambuco, Recife, PE, Brazil.
[Moss, Nancy] NICHD, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Spinnato, Joseph, II] Univ S Florida, Tampa, FL USA.
RI Rudge, Marilza /C-8338-2012
OI Rudge, Marilza /0000-0002-9227-832X
NR 0
TC 1
Z9 1
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 95
BP S57
EP S57
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900096
ER
PT J
AU Silver, B
AF Silver, Bob
TI First trimester free total and fetal DNA in the maternal circulation are
not associated with preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Silver, Bob] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 744
BP S330
EP S330
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889901010
ER
PT J
AU Sutton, A
AF Sutton, Amelia
TI The impact of delivery timing on cesarean delivery risk in women with
mild destational diabetes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Sutton, Amelia] Eunice Kennedy Shriver Natl Inst Child Hlth, Bethesda, MD USA.
[Sutton, Amelia] Human Dev Maternal Fetal Med Units Network, Bethesda, MD USA.
OI Sutton, Amelia/0000-0003-0493-0670
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 279
BP S135
EP S135
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900279
ER
PT J
AU Tita, A
AF Tita, Alan
TI Maternal and perinatal morbidity risks differ by type of
pregnancy-associated hypertension in nulliparas
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Tita, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 734
BP S325
EP S325
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900729
ER
PT J
AU Tita, A
AF Tita, Alan
TI Pregnancy associated hypertension: cumulative risk varies by subtype,
race and body mass index
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Tita, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 JAN
PY 2012
VL 206
IS 1
SU S
MA 735
BP S326
EP S326
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889901001
ER
PT J
AU Tita, A
AF Tita, Alan
TI Burden of adverse maternal and perinatal outcomes by preterm birth type
in nulliparas
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Tita, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 JAN
PY 2012
VL 206
IS 1
SU S
MA 452
BP S207
EP S208
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900451
ER
PT J
AU Wapner, R
AF Wapner, Ronald
TI A multicenter, prospective, masked comparison of chromosomal microarray
with standard karyotyping for routine and high risk prenatal diagnosis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting/Pregnancy Meeting of
Society-for-Maternal-Fetal-Medicine
CY FEB 06-11, 2012
CL Dallas, TX
SP Soc Maternal Fetal Med
C1 [Wapner, Ronald] NICHD, Prenatal Microarray Study Grp, Bethesda, MD USA.
NR 0
TC 16
Z9 17
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2012
VL 206
IS 1
SU S
MA 1
BP S2
EP S2
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 873NL
UT WOS:000298889900002
ER
PT J
AU Dorsey, SG
Lovering, RM
Renn, CL
Leitch, CC
Liu, XY
Tallon, LJ
Sadzewicz, LD
Pratap, A
Ott, S
Sengamalay, N
Jones, KM
Barrick, C
Fulgenzi, G
Becker, J
Voelker, K
Talmadge, R
Harvey, BK
Wyatt, RM
Vernon-Pitts, E
Zhang, C
Shokat, K
Fraser-Liggett, C
Balice-Gordon, RJ
Tessarollo, L
Ward, CW
AF Dorsey, Susan G.
Lovering, Richard M.
Renn, Cynthia L.
Leitch, Carmen C.
Liu, Xinyue
Tallon, Luke J.
Sadzewicz, Lisa DeShong
Pratap, Abhishek
Ott, Sandra
Sengamalay, Naomi
Jones, Kristie M.
Barrick, Colleen
Fulgenzi, Gianluca
Becker, Jodi
Voelker, Kevin
Talmadge, Robert
Harvey, Brandon K.
Wyatt, Ryan M.
Vernon-Pitts, Elizabeth
Zhang, Chao
Shokat, Kevan
Fraser-Liggett, Claire
Balice-Gordon, Rita J.
Tessarollo, Lino
Ward, Christopher W.
TI Genetic deletion of trkB.T1 increases neuromuscular function
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE neurotrophin; neuromuscular junction; calcium; knockout mouse
ID MOUSE SKELETAL-MUSCLE; CONTRACTION-INDUCED INJURY; FIBER-TYPE
PLASTICITY; NEUROTROPHIC FACTOR; SIGNALING PATHWAYS; IN-VIVO; ECCENTRIC
CONTRACTIONS; MUSCULAR-DYSTROPHY; TRK RECEPTORS; CA2+ SPARKS
AB Dorsey SG, Lovering RM, Renn CL, Leitch CC, Liu X, Tallon LJ, Sadzewicz LD, Pratap A, Ott S, Sengamalay N, Jones KM, Barrick C, Fulgenzi G, Becker J, Voelker K, Talmadge R, Harvey BK, Wyatt RM, Vernon-Pitts E, Zhang C, Shokat K, Fraser-Liggett C, Balice-Gordon RJ, Tessarollo L, Ward CW. Genetic deletion of trkB.T1 increases neuromuscular function. Am J Physiol Cell Physiol 302: C141-C153, 2012. First published August 24, 2011; doi:10.1152/ajpcell.00469.2010.-Neurotrophin-dependent activation of the tyrosine kinase receptor trkB. FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB (trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1(-/-) animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB. FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.
C1 [Dorsey, Susan G.; Renn, Cynthia L.; Leitch, Carmen C.; Ward, Christopher W.] Univ Maryland Baltimore, Sch Nursing, Baltimore, MD USA.
[Lovering, Richard M.] Univ Maryland Baltimore, Sch Med, Baltimore, MD USA.
[Voelker, Kevin] Virginia Tech, Dept Human Nutr Foods & Exercise, Blacksburg, VA USA.
[Talmadge, Robert] Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA.
[Harvey, Brandon K.] NIDA, NIH, Bethesda, MD 20892 USA.
[Wyatt, Ryan M.; Vernon-Pitts, Elizabeth; Balice-Gordon, Rita J.] Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA.
[Barrick, Colleen; Fulgenzi, Gianluca; Becker, Jodi; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Zhang, Chao; Shokat, Kevan] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Liu, Xinyue; Tallon, Luke J.; Sadzewicz, Lisa DeShong; Pratap, Abhishek; Ott, Sandra; Sengamalay, Naomi; Jones, Kristie M.; Fraser-Liggett, Claire] Univ Maryland Baltimore, Sch Med, Inst Genome Sci, Baltimore, MD USA.
RP Ward, CW (reprint author), Univ Maryland, Sch Nursing, 655 W Lombard St,Rm 752, Baltimore, MD 21201 USA.
EM sdorsey@son.umaryland.edu; ward@son.umaryland.edu
OI Fraser, Claire/0000-0003-1462-2428; Fulgenzi,
Gianluca/0000-0003-2646-7728
FU National Institutes of Health [AR002177, AR053318, RC2 NR011968,
NR009672, NR011968, NS047777, K01AR053235, 1R01AR059179, NS046490];
National Cancer Institute Center for Cancer Research; National Institute
of Drug Abuse
FX This work was supported by grants from the National Institutes of Health
to C. W. Ward (AR002177, AR053318, and RC2 NR011968), to S. G. Dorsey
(NR009672 and NR011968), to R. M. Wyatt (NS047777), to R. Lovering
(K01AR053235 and 1R01AR059179), and to R. Balice-Gordon (NS046490), and
by intramural support from the National Cancer Institute Center for
Cancer Research to C. Barrick and L. J. Tallon and intramural support
from the National Institute of Drug Abuse to B. K. Harvey.
NR 76
TC 8
Z9 8
U1 1
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2012
VL 302
IS 1
BP C141
EP C153
DI 10.1152/ajpcell.00469.2010
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 866IN
UT WOS:000298374100017
PM 21865582
ER
PT J
AU Pisitkun, T
Hoffert, JD
Saeed, F
Knepper, MA
AF Pisitkun, Trairak
Hoffert, Jason D.
Saeed, Fahad
Knepper, Mark A.
TI NHLBI-AbDesigner: an online tool for design of peptide-directed
antibodies
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE immunogenicity; posttranslational modification; specificity; epitope;
conservation
ID THICK ASCENDING LIMB; LONG-TERM REGULATION; RAT-KIDNEY; COLLECTING DUCT;
WATER CHANNEL; PLASMA-MEMBRANE; AQUAPORIN-2 PHOSPHORYLATION;
VASOPRESSIN; LOCALIZATION; EXPRESSION
AB Pisitkun T, Hoffert JD, Saeed F, Knepper MA. NHLBI-AbDesigner: an online tool for design of peptide-directed antibodies. Am J Physiol Cell Physiol 302: C154-C164, 2012. First published September 28, 2011; doi:10.1152/ajpcell.00325.2011.-Investigation of physiological mechanisms at a cellular level often requires production of high-quality antibodies, frequently using synthetic peptides as immunogens. Here we describe a new, web-based software tool called NHLBI-AbDesigner that allows the user to visualize the information needed to choose optimal peptide sequences for peptide-directed antibody production (http://helixweb.nih.gov/AbDesigner/). The choice of an immunizing peptide is generally based on a need to optimize immunogenicity, antibody specificity, multispecies conservation, and robustness in the face of posttranslational modifications (PTMs). AbDesigner displays information relevant to these criteria as follows: 1) "Immunogenicity Score," based on hydropathy and secondary structure prediction; 2) "Uniqueness Score," a predictor of specificity of an antibody against all proteins expressed in the same species; 3) "Conservation Score," a predictor of ability of the antibody to recognize orthologs in other animal species; and 4) "Protein Features" that show structural domains, variable regions, and annotated PTMs that may affect antibody performance. AbDesigner displays the information online in an interactive graphical user interface, which allows the user to recognize the trade-offs that exist for alternative synthetic peptide choices and to choose the one that is best for a proposed application. Several examples of the use of AbDesigner for the display of such trade-offs are presented, including production of a new antibody to Slc9a3. We also used the program in large-scale mode to create a database listing the 15-amino acid peptides with the highest Immunogenicity Scores for all known proteins in five animal species, one plant species (Arabidopsis thaliana), and Saccharomyces cerevisiae.
C1 [Pisitkun, Trairak; Hoffert, Jason D.; Saeed, Fahad; Knepper, Mark 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, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
RI Saeed, Fahad/D-1545-2013;
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Intramural Budget of the National Heart, Lung, and Blood Institute
[Z01-HL-001285]
FX This work was supported by the Intramural Budget of the National Heart,
Lung, and Blood Institute (Project Z01-HL-001285).
NR 37
TC 9
Z9 9
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2012
VL 302
IS 1
BP C154
EP C164
DI 10.1152/ajpcell.00325.2011
PG 11
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 866IN
UT WOS:000298374100018
PM 21956165
ER
PT J
AU Pla, AF
Avanzato, D
Munaron, L
Ambudkar, IS
AF Pla, Alessandra Fiorio
Avanzato, Daniele
Munaron, Luca
Ambudkar, Indu S.
TI Ion channels and transporters in cancer. 6. Vascularizing the tumor: TRP
channels as molecular targets
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE tumor vascularization; endothelial cells; calcium ions; transient
receptor potential channels
ID ENDOTHELIAL PROGENITOR CELLS; RECEPTOR POTENTIAL CHANNELS; OPERATED CA2+
ENTRY; ARACHIDONIC-ACID; PLASMA-MEMBRANE; CATION CHANNELS;
CALCIUM-ENTRY; IN-VIVO; ANGIOGENESIS; PERMEABILITY
AB Fiorio Pla A, Avanzato D, Munaron L, Ambudkar IS. Ion channels and transporters in cancer. 6. Vascularizing the tumor: TRP channels as molecular targets. Am J Physiol Cell Physiol 302: C9-C15, 2012. First published August 10, 2011; doi:10.1152/ajpcell.00280.2011.-Tumor vascularization is a critical process that determines tumor growth and metastasis. In the last decade new experimental evidence obtained from in vitro and in vivo studies have challenged the classical angiogenesis model forcing us to consider new scenarios for tumor neovascularization. In particular, the genetic stability of tumor-derived endothelial cells (TECs) has been recently questioned in several studies, which show that TECs, as well as pericytes, differ significantly from their normal counterparts at genetic and functional levels. In addition to such an epigenetic action of tumor microenvironment on endothelial cells (ECs) commitment, the distinct characteristics of TECs could be due to differences in their origin compared with preexisting differentiated ECs. Intracellular Ca(2+) signals are involved at different critical phases in the regulation of the complex process of angiogenesis and tumor progression. These signals are generated by a wide variety of intrinsic and extrinsic factors. Several key components of Ca(2+) signaling including Ca(2+) channels in the plasma membrane, endoplasmic reticulum, calcium pumps, and mitochondria contribute to the generation, amplitude, and frequency of these Ca(2+) change. In particular, several members of the transient receptor potential (TRP) family of calcium-permeable channels have profound effects on the function of ECs. Because of its multifaceted role in the control of cell function, proliferation, and motility, TRP channels have been suggested as a potential molecular target for control of tumor neovascularization. Since plasma membrane Ca(2+) channels are easily and directly accessible via the bloodstream, they are potential targets for a number of pharmacological and antibody-targeted therapeutic strategies, with specificity being the main limitation. In this review we discuss recent advances in understanding the role of Ca(2+) channels, with specific reference to TRP channels, in tumor vascularization process.
C1 [Pla, Alessandra Fiorio; Avanzato, Daniele; Munaron, Luca] Univ Turin, Dept Anim & Human Biol, I-10123 Turin, Italy.
[Pla, Alessandra Fiorio; Munaron, Luca] Univ Turin, Ctr Complex Syst Mol Biol & Med SysBioM, I-10123 Turin, Italy.
[Pla, Alessandra Fiorio; Munaron, Luca] Univ Turin, Nanostruct Interfaces & Surfaces Ctr Excelle, I-10123 Turin, Italy.
[Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Pla, AF (reprint author), Univ Turin, Dept Anim & Human Biol, V Accademia Albertina 13, I-10123 Turin, Italy.
EM alessandra.fiorio@unito.it
RI Fiorio Pla, Alessandra/B-6646-2012
OI Fiorio Pla, Alessandra/0000-0003-4576-1594
NR 73
TC 33
Z9 33
U1 1
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2012
VL 302
IS 1
BP C9
EP C15
DI 10.1152/ajpcell.00280.2011
PG 7
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 866IN
UT WOS:000298374100002
ER
PT J
AU Zhao, BY
Knepper, MA
Chou, CL
Pisitkun, T
AF Zhao, Boyang
Knepper, Mark A.
Chou, Chung-Lin
Pisitkun, Trairak
TI Large-scale phosphotyrosine proteomic profiling of rat renal collecting
duct epithelium reveals predominance of proteins involved in cell
polarity determination
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE mass spectrometry; kidney; adherens junction; tight junction;
cytoskeleton
ID TANDEM MASS-SPECTRA; TYROSINE PHOSPHORYLATION; PHOSPHOPROTEOMIC
ANALYSIS; TIGHT JUNCTIONS; QUANTITATIVE PHOSPHOPROTEOMICS; SIGNALING
PATHWAYS; FOCAL ADHESION; IN-VIVO; NETWORKS; SPECTROMETRY
AB Zhao B, Knepper MA, Chou CL, Pisitkun T. Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination. Am J Physiol Cell Physiol 302: C27-C45, 2012. First published September 21, 2011; doi:10.1152/ajpcell.00300.2011.-Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin-and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions ("adherens junction," "tight junction," and "focal adhesion") and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.
C1 [Zhao, Boyang; Knepper, Mark A.; Chou, Chung-Lin; Pisitkun, Trairak] 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, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Intramural Budget of the NHLBI [Z01-HL-001285]; National Institute of
Biomedical Imaging and Bioengineering
FX The authors thank Jennifer Huling from National Heart, Lung, and Blood
Institute (NHLBI) for help in setting up the Rat Inner Medullary
Collecting Duct Phosphotyrosine Database and Aleksandra Nita-Lazar from
National Institute of Allergy and Infectious Diseases for information on
the antiphosphotyrosine peptide immunoprecipitation protocol. This study
was supported by the Intramural Budget of the NHLBI (NHLBI Project
Z01-HL-001285). Mass spectrometry was done in the NHLBI Proteomics Core
Facility (Marjan Gucek, Director). Boyang Zhao was a student intern from
the University of Michigan in the National Institutes of Health
Biomedical Engineering Summer Internship Program, funded by the National
Institute of Biomedical Imaging and Bioengineering (present e-mail:
bozhao@mit.edu).
NR 70
TC 5
Z9 5
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2012
VL 302
IS 1
BP C27
EP C45
DI 10.1152/ajpcell.00300.2011
PG 19
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 866IN
UT WOS:000298374100007
PM 21940666
ER
PT J
AU Ernst, PB
Erickson, LD
Loo, WM
Scott, KG
Wiznerowicz, EB
Brown, CC
Torres-Velez, FJ
Alam, MS
Black, SG
McDuffie, M
Feldman, SH
Wallace, JL
McKnight, GW
Padol, IT
Hunt, RH
Tung, KS
AF Ernst, P. B.
Erickson, L. D.
Loo, W. M.
Scott, K. G.
Wiznerowicz, E. B.
Brown, C. C.
Torres-Velez, F. J.
Alam, M. S.
Black, S. G.
McDuffie, M.
Feldman, S. H.
Wallace, J. L.
McKnight, G. W.
Padol, I. T.
Hunt, R. H.
Tung, K. S.
TI Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the
ileitis-prone SAMP1/YitFcs mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE parietal cell; autoantibodies; autoimmune gastritis; model of Crohn's
disease
ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; HELICOBACTER-PYLORI;
CROHNS-DISEASE; MURINE MODEL; INTESTINAL INFLAMMATION; CYTOKINE
PRODUCTION; CUTTING EDGE; B-CELLS; MOUSE
AB Ernst PB, Erickson LD, Loo WM, Scott KG, Wiznerowicz EB, Brown CC, Torres-Velez FJ, Alam MS, Black SG, McDuffie M, Feldman SH, Wallace JL, McKnight GW, Padol IT, Hunt RH, Tung KS. Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice. Am J Physiol Gastrointest Liver Physiol 302: G105-G115, 2012. First published September 15, 2011; doi:10.1152/ajpgi.00194.2011.-SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD(4+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.
C1 [Ernst, P. B.; Erickson, L. D.; Loo, W. M.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
[Ernst, P. B.; Wiznerowicz, E. B.; Black, S. G.] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
[McDuffie, M.] Univ Virginia, Dept Pediat, Charlottesville, VA 22908 USA.
[Tung, K. S.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
[Feldman, S. H.] Univ Virginia, Ctr Comparat Med, Charlottesville, VA 22908 USA.
[Scott, K. G.] Univ Manitoba, Dept Biol, Winnipeg, MB, Canada.
[Wallace, J. L.; McKnight, G. W.; Padol, I. T.; Hunt, R. H.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Wallace, J. L.; McKnight, G. W.; Padol, I. T.; Hunt, R. H.] McMaster Univ, Farncombe Inst, Hamilton, ON, Canada.
[Brown, C. C.] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA.
[Torres-Velez, F. J.] NIAID, Infect Dis Pathogenesis Sect, Bethesda, MD 20892 USA.
[Alam, M. S.] US FDA, Immunobiol Branch, Ctr Food Safety & Nutr, Laurel, MD USA.
RP Ernst, PB (reprint author), Univ Calif San Diego, Dept Pathol, Div Comparat Pathol & Med, 9500 Gilman Dr,MC 0063, La Jolla, CA 92093 USA.
EM pernst@ucsd.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK-051677, DK-84063]; Canadian Association of Gastroenterology;
National Institute of Allergy and Infectious Diseases [AI-41236,
AI-51420, DK 57880]
FX This research was supported by National Institute of Diabetes and
Digestive and Kidney Diseases Grants DK-051677 and DK-84063 (to P. B.
Ernst), a Research Fellowship from the Canadian Association of
Gastroenterology (to K. G. Scott), National Institute of Allergy and
Infectious Diseases AI-41236 and AI-51420 (to K. S. Tung), and DK 57880
(M. McDuffie).
NR 45
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Z9 0
U1 0
U2 0
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 JAN
PY 2012
VL 302
IS 1
BP G105
EP G115
DI 10.1152/ajpgi.00194.2011
PG 11
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 869ZZ
UT WOS:000298640200011
PM 21921286
ER
PT J
AU Chantler, PD
Melenovsky, V
Schulman, SP
Gerstenblith, G
Becker, LC
Ferrucci, L
Fleg, JL
Lakatta, EG
Najjar, SS
AF Chantler, Paul D.
Melenovsky, Vojtech
Schulman, Steven P.
Gerstenblith, Gary
Becker, Lewis C.
Ferrucci, Luigi
Fleg, Jerome L.
Lakatta, Edward G.
Najjar, Samer S.
TI Use of the Frank-Starling mechanism during exercise is linked to
exercise-induced changes in arterial load
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE arterial elastance; cardiovascular performance
ID PRESERVED EJECTION FRACTION; BLOOD-PRESSURE RESPONSE; SYSTEMIC
VASCULAR-RESISTANCE; HEART-FAILURE; CARDIAC-OUTPUT;
CARDIOVASCULAR-RESPONSES; STROKE VOLUME; HEALTHY-MEN; WAVE-FORM; HUMANS
AB Chantler PD, Melenovsky V, Schulman SP, Gerstenblith G, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Use of the Frank-Starling mechanism during exercise is linked to exercise- induced changes in arterial load. Am J Physiol Heart Circ Physiol 302: H349-H358, 2012. First published October 14, 2011; doi: 10.1152/ajpheart.00147.2011.-Effective arterial elastance(E(A)) is a measure of the net arterial load imposed on the heart that integrates the effects of heart rate(HR), peripheral vascular resistance( PVR), and total arterial compliance(TAC) and is a modulator of cardiac performance. To what extent the change in E(A) during exercise impacts on cardiac performance and aerobic capacity is unknown. We examined E(A) and its relationship with cardiovascular performance in 352 healthy subjects. Subjects underwent rest and exercise gated scans to measure cardiac volumes and to derive E(A)[end-systolic pressure/stroke volume index(SV)], PVR[MAP/(SV*HR)], and TAC(SV/pulse pressure). E(A) varied with exercise intensity: the Delta E(A) between rest and peak exercise along with its determinants, differed among individuals and ranged from -44% to +149%, and was independent of age and sex. Individuals were separated into 3 groups based on their Delta E(A)I. Individuals with the largest increase in Delta E(A)(group 3;Delta E(A) >= 0.98 mmHg.m(2)/ml) had the smallest reduction in PVR, the greatest reduction in TAC and a similar increase in HR vs. group 1(Delta E(A) < 0.22 mmHg.m(2)/ml). Furthermore, group 3 had a reduction in end-diastolic volume, and a blunted increase in SV(80%), and cardiac output(27%), during exercise vs. group 1. Despite limitations in the Frank-Starling mechanism and cardiac function, peak aerobic capacity did not differ by group because arterial-venous oxygen difference was greater in group 3 vs. 1. Thus the change in arterial load during exercise has important effects on the Frank-Starling mechanism and cardiac performance but not on exercise capacity. These findings provide interesting insights into the dynamic cardiovascular alterations during exercise.
C1 [Chantler, Paul D.; Melenovsky, Vojtech; Ferrucci, Luigi; Fleg, Jerome L.; Lakatta, Edward G.; Najjar, Samer S.] NIA, Intramural Res Program, Baltimore, MD 21225 USA.
[Chantler, Paul D.] W Virginia Univ, Dept Exercise Physiol, Sch Med, Morgantown, WV 26506 USA.
[Melenovsky, Vojtech] Inst Clin & Expt Med, Dept Cardiol, Prague, Czech Republic.
[Schulman, Steven P.; Gerstenblith, Gary; Becker, Lewis C.] Johns Hopkins Univ Baltimore, Div Cardiol, Baltimore, MD USA.
RP Lakatta, EG (reprint author), NIA, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21225 USA.
EM lakattae@grc.nia.nih.gov
OI Melenovsky, Vojtech/0000-0001-8921-7078
FU NIH, National Institute on Aging; State Department of Health, Czech
Republic [NS 10497-3/2009]; [N01AG82109]
FX This work was supported by contract N01AG82109 (Gary Gerstenblith), and,
in part, by the Intramural Research Program of the NIH, National
Institute on Aging. VM is currently supported from the State Department
of Health, Czech Republic (grant NS 10497-3/2009).
NR 52
TC 8
Z9 8
U1 2
U2 16
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JAN
PY 2012
VL 302
IS 1
BP H349
EP H358
DI 10.1152/ajpheart.00147.2011
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 870BJ
UT WOS:000298643800035
PM 22003052
ER
PT J
AU Yao, XL
Dai, CL
Fredriksson, K
Lam, J
Gao, MX
Keeran, KJ
Nugent, GZ
Qu, X
Yu, ZX
Jeffries, N
Lin, JP
Kaler, M
Shamburek, R
Costello, R
Csako, G
Dahl, M
Nordestgaard, BG
Remaley, AT
Levine, SJ
AF Yao, Xianglan
Dai, Cuilian
Fredriksson, Karin
Lam, Jonathan
Gao, Meixia
Keeran, Karen J.
Nugent, Gayle Zywicke
Qu, Xuan
Yu, Zu-Xi
Jeffries, Neal
Lin, JingPing
Kaler, Maryann
Shamburek, Robert
Costello, Rene
Csako, Gyorgy
Dahl, Morten
Nordestgaard, Borge G.
Remaley, Alan T.
Levine, Stewart J.
TI Human apolipoprotein E genotypes differentially modify house dust
mite-induced airway disease in mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE asthma
ID OBSTRUCTIVE PULMONARY-DISEASE; E-DEFICIENT MICE; APOE GENOTYPE; ASTHMA;
ASSOCIATION; ATHEROSCLEROSIS; RISK; HYPERCHOLESTEROLEMIA; CELLS; GENE
AB Yao X, Dai C, Fredriksson K, Lam J, Gao M, Keeran KJ, Nugent GZ, Qu X, Yu Z-X, Jeffries N, Lin J, Kaler M, Shamburek R, Costello R, Csako G, Dahl M, Nordestgaard BG, Remaley AT, Levine SJ. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice. Am J Physiol Lung Cell Mol Physiol 302: L206-L215, 2012. First published November 4, 2011; doi:10.1152/ajplung.00110.2011.-Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (epsilon 2, epsilon 3, and epsilon 4) reflecting single amino acid substitutions at amino acids 112 and 158. The objective of this study was to assess whether the human apoE alleles modify airway responses to repeated nasal HDM challenges. Mice expressing the human apoE epsilon 2 (huApoE2), epsilon 3 (huApoE3), or epsilon 4 (huApoE4) alleles received nasal HDM challenges, and airway responses were compared with mice expressing the endogenous murine apoE gene (muApoE). huApoE3 mice displayed significant reductions in AHR, mucous cell metaplasia, and airway inflammation compared with muApoE mice. The attenuated severity of airway inflammation in huApoE3 mice was associated with reductions in lung mRNA levels of Th2 and Th17 cytokines, as well as chemokines (CCL7, CCL11, CCL24). huApoE4 mice had an intermediate phenotype, with attenuated AHR and IgE production, compared with muApoE mice, whereas airway inflammation and mucous cell metaplasia were not reduced. In contrast, HDM-induced airway responses were not modified in mice expressing the huApoE2 allele. We conclude that the polymorphic huApoE alleles differentially modulate HDM-induced airway disease, which can be stratified, in rank order of increasing disease severity, epsilon 3 < epsilon 4 < epsilon 2. These results raise the possibility that the polymorphic apoE alleles may modify disease severity in human asthma.
C1 [Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin; Lam, Jonathan; Gao, Meixia; Kaler, Maryann; Shamburek, Robert; Remaley, Alan T.; Levine, Stewart J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Keeran, Karen J.; Nugent, Gayle Zywicke] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA.
[Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA.
[Jeffries, Neal; Lin, JingPing] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Costello, Rene; Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Dahl, Morten; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
RP Levine, SJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Rm 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov
RI Dahl, Morten/F-4219-2014
OI Dahl, Morten/0000-0002-6686-312X
FU Division of Intramural Research; NHLBI; NIH; Department of Laboratory
Medicine, Clinical Center, NIH
FX This work was funded by the Division of Intramural Research, NHLBI, NIH
and the Department of Laboratory Medicine, Clinical Center, NIH.
NR 42
TC 9
Z9 9
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JAN
PY 2012
VL 302
IS 2
BP L206
EP L215
DI 10.1152/ajplung.00110.2011
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 875EP
UT WOS:000299013500003
PM 22058162
ER
PT J
AU Stringaris, A
Zavos, H
Leibenluft, E
Maughan, B
Eley, TC
AF Stringaris, Argyris
Zavos, Helena
Leibenluft, Ellen
Maughan, Barbara
Eley, Thalia C.
TI Adolescent Irritability: Phenotypic Associations and Genetic Links With
Depressed Mood
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID OPPOSITIONAL DEFIANT DISORDER; ANTISOCIAL-BEHAVIOR; ATTRIBUTIONAL STYLE;
MAJOR DEPRESSION; CONDUCT DISORDER; CHILDREN; PREDICTORS; YOUTH;
DIMENSIONS; CHILDHOOD
AB Objective: Irritability has been proposed to underlie the developmental link between oppositional problems and depression. Little is known, however, about the genetic and environmental influences on irritability and its overlap with depression. Drawing on the notion of "generalist genes" (genes of general effect that underlie phenotypic overlap between disorders), the authors test the hypothesis that the association between irritability and depression is accounted for by genetic factors.
Method: Data from the G1219 study, a U.K. twin/sibling sample (N=2,651), were used in a cross-sectional and longitudinal design. The irritable and headstrong/hurtful dimensions of oppositional behavior were derived using factor analysis. Regression was used to estimate the association between depression and delinquency. Multivariate genetic analyses were used to estimate the genetic overlaps between the two components of oppositionality (irritability and headstrong/hurtful behaviors) and depression and delinquency.
Results: Irritability showed a significantly stronger phenotypic relationship with depression than with delinquency, whereas headstrong/hurtful behaviors were more strongly related to delinquency than to depression. In multivariate genetic analyses, the genetic correlation between irritability and depression (r(A)=0.70, 95% CI=0.59-0.82) was significantly higher than that between irritability and delinquency (r(A)=0.57, 95% CI=0.45-0.69); conversely, the genetic correlation between headstrong/hurtful behaviors and delinquency (r(A)=0.80, 95% CI=0.72-0.86) was significantly higher than that between headstrong/hurtful behaviors and depression (r(A)=0.46, 95% CI=0.36-0.57). In longitudinal models, the phenotypic association between irritability at wave 2 and depression at wave 3 was accounted for by the genetic association between irritability and depression at wave 2.
Conclusions: These findings are consistent with the theory that genes with general effects underlie the relationship between irritability and depression.
C1 [Stringaris, Argyris] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England.
Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England.
NIMH, Sect Bipolar Spectrum Disorders, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
RP Stringaris, A (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England.
EM argyris.stringaris@kcl.ac.uk
RI Zavos, Helena/B-2153-2013
FU Wellcome Trust
FX Dr. Stringaris gratefully acknowledges the support of the Wellcome
Trust.
NR 34
TC 69
Z9 70
U1 1
U2 22
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 JAN
PY 2012
VL 169
IS 1
BP 47
EP 54
DI 10.1176/appi.ajp.2011.10101549
PG 8
WC Psychiatry
SC Psychiatry
GA 875UQ
UT WOS:000299061100011
PM 22193524
ER
PT J
AU Hall, EC
Pfeiffer, RM
Engels, EA
Segev, DL
AF Hall, Erin C.
Pfeiffer, Ruth M.
Engels, Eric A.
Segev, Dorry L.
TI Association of Induction Therapy with Cancer after Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American-Society-of-Transplant-Surgeons (ASTS) 12th Annual State of the
Art Winter Symposium/North-American-Transplant-Coordinators-Organization
(NATCO) Symposium for Advanced Transplant Professionals
CY JAN 12-15, 2012
CL Miami, FL
SP Amer Soc Transplant Surg (ASTS), N Amer Transplant Coordinators Org (NATCO)
C1 [Hall, Erin C.; Segev, Dorry L.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Hall, Erin C.; Pfeiffer, Ruth M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JAN
PY 2012
VL 12
SU 2
SI SI
BP 63
EP 63
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 867UW
UT WOS:000298481300033
ER
PT J
AU Hall, EC
Pfeiffer, RM
Segev, DL
Engels, EA
AF Hall, Erin C.
Pfeiffer, Ruth M.
Segev, Dorry L.
Engels, Eric A.
TI Cumulative Incidence of Cancer after Solid Organ Transplant
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American-Society-of-Transplant-Surgeons (ASTS) 12th Annual State of the
Art Winter Symposium/North-American-Transplant-Coordinators-Organization
(NATCO) Symposium for Advanced Transplant Professionals
CY JAN 12-15, 2012
CL Miami, FL
SP Amer Soc Transplant Surg (ASTS), N Amer Transplant Coordinators Org (NATCO)
C1 [Hall, Erin C.; Pfeiffer, Ruth M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hall, Erin C.; Segev, Dorry L.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JAN
PY 2012
VL 12
SU 2
SI SI
BP 92
EP 92
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 867UW
UT WOS:000298481300122
ER
PT J
AU Sander, LC
Bedner, M
Tims, MC
Yen, JH
Duewer, DL
Porter, B
Christopher, SJ
Day, RD
Long, SE
Molloy, JL
Murphy, KE
Lang, BE
Lieberman, R
Wood, LJ
Payne, MJ
Roman, MC
Betz, JM
NguyenPho, A
Sharpless, KE
Wise, SA
AF Sander, L. C.
Bedner, M.
Tims, M. C.
Yen, J. H.
Duewer, D. L.
Porter, B.
Christopher, S. J.
Day, R. D.
Long, S. E.
Molloy, J. L.
Murphy, K. E.
Lang, B. E.
Lieberman, R.
Wood, L. J.
Payne, M. J.
Roman, M. C.
Betz, J. M.
NguyenPho, A.
Sharpless, K. E.
Wise, S. A.
TI Development and certification of green tea-containing standard reference
materials
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Green tea; Camellia sinensis; Standard Reference Material; Catechins;
Xanthines; Toxic elements; Theanine
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MICELLAR ELECTROKINETIC
CHROMATOGRAPHY; COULOMETRIC ARRAY DETECTION; IONIZATION
MASS-SPECTROMETRY; MS-ELECTROSPRAY DETECTION; COMMERCIAL CANNED GREEN;
SOLID-PHASE EXTRACTION; GALLIC ACID; PURINE ALKALOIDS; INDIVIDUAL
CATECHINS
AB A suite of three green tea-containing Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST): SRM 3254 Camellia sinensis (Green Tea) Leaves, SRM 3255 Camellia sinensis (Green Tea) Extract, and SRM 3256 Green Tea-Containing Solid Oral Dosage Form. The materials are characterized for catechins, xanthine alkaloids, theanine, and toxic elements. As many as five methods were used in assigning certified and reference values to the constituents, with measurements carried out at NIST and at collaborating laboratories. The materials are intended for use in the development and validation of new analytical methods, and for use as control materials as a component in the support of claims of metrological traceability.
C1 [Sander, L. C.; Bedner, M.; Tims, M. C.; Duewer, D. L.; Porter, B.; Long, S. E.; Molloy, J. L.; Murphy, K. E.; Lieberman, R.; Wood, L. J.; Sharpless, K. E.; Wise, S. A.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
[Yen, J. H.] NIST, Stat Engn Div, Gaithersburg, MD 20899 USA.
[Christopher, S. J.; Day, R. D.] NIST, Div Analyt Chem, Charleston, SC 29412 USA.
[Lang, B. E.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Payne, M. J.] Hershey Co, Hershey, PA 17033 USA.
[Roman, M. C.] Tampa Bay Analyt Res Inc, Largo, FL 33777 USA.
[Betz, J. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[NguyenPho, A.] US FDA, Ctr Drug Evaluat & Res CDER, Silver Spring, MD 20993 USA.
RP Sander, LC (reprint author), NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
EM lane.sander@nist.gov
FU National Institutes of Health, Office of Dietary Supplements
FX Partial funding for this work was provided by the National Institutes of
Health, Office of Dietary Supplements. M. Schantz and E. McGaw (NIST)
are acknowledged for pesticide screening of the three SRMs.
NR 59
TC 15
Z9 15
U1 0
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JAN
PY 2012
VL 402
IS 1
BP 473
EP 487
DI 10.1007/s00216-011-5472-7
PG 15
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 871PE
UT WOS:000298749300051
PM 22127575
ER
PT J
AU Liu, G
Choi, KY
Bhirde, A
Swierczewska, M
Yin, J
Lee, SW
Park, JH
Hong, JI
Xie, J
Niu, G
Kiesewetter, DO
Lee, S
Chen, XY
AF Liu, Gang
Choi, Ki Young
Bhirde, Ashwinkumar
Swierczewska, Magdalena
Yin, Juan
Lee, Sang Wook
Park, Jae Hyung
Hong, Jong In
Xie, Jin
Niu, Gang
Kiesewetter, Dale O.
Lee, Seulki
Chen, Xiaoyuan
TI Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II)
dipicolylamine)-Functionalized, Self-Assembled Nanoconjugate
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE dipicolylamines; drug delivery; hyaluronic acid; nanoparticles; siRNA
ID THERAPEUTICS; HYALURONAN; RECEPTOR; PROBE
C1 [Liu, Gang; Choi, Ki Young; Bhirde, Ashwinkumar; Swierczewska, Magdalena; Niu, Gang; Kiesewetter, Dale O.; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
[Liu, Gang] N Sichuan Med Coll, Sichuan Key Lab Med Imaging, Chengtu, Peoples R China.
[Yin, Juan] NCI, NIH, Bethesda, MD 20892 USA.
[Lee, Sang Wook; Hong, Jong In] Seoul Natl Univ, Dept Chem, Seoul 151, South Korea.
[Park, Jae Hyung] Sungkyunkwan Univ, Dept Polymer Sci & Engn, Seoul, South Korea.
[Xie, Jin] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Xie, Jin] Univ Georgia, Bioimaging Res Ctr, Athens, GA 30602 USA.
RP Lee, S (reprint author), Natl Inst Biomed Imaging & Bioengn NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
EM seulki.lee@nih.gov; shawn.chen@nih.gov
RI byun, jaehyun/G-5584-2014; CHOI, KI YOUNG/Q-7177-2016
FU NIBIB, NIH; NIH [K99/R00]; National Natural Science Foundation of China
(NSFC) [81101101, 2011JQ0032, 81028009]; MEST (Korea) [2009-0080734]
FX This work was supported by the Intramural Research Program of the NIBIB,
NIH and partially supported by an NIH Pathway to Independence (K99/R00)
Award, the National Natural Science Foundation of China (NSFC, grant
nos. 81101101 and 2011JQ0032), the International Cooperative Program of
the NSFC (grant no. 81028009), and NRF grant 2009-0080734 from the MEST
(Korea).
NR 25
TC 38
Z9 39
U1 1
U2 51
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1433-7851
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PY 2012
VL 51
IS 2
BP 445
EP 449
DI 10.1002/anie.201105565
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 872ER
UT WOS:000298792100018
PM 22110006
ER
PT J
AU Liu, Z
Zhang, WP
Xing, Q
Ren, XF
Liu, ML
Tang, C
AF Liu, Zhu
Zhang, Wei-Ping
Xing, Qiong
Ren, Xuefeng
Liu, Maili
Tang, Chun
TI Noncovalent Dimerization of Ubiquitin
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE dimerization; NMR spectroscopy; paramagnetic relaxation enhancement;
protein-protein interactions; ubiquitin
ID PARAMAGNETIC RELAXATION ENHANCEMENT; PROTEIN-PROTEIN ASSOCIATION;
TRANSIENT ENCOUNTER COMPLEXES; STRUCTURAL BASIS; POLYUBIQUITIN CHAINS;
BINDING DOMAINS; NMR; TETRAUBIQUITIN; RECOGNITION; MACROMOLECULES
C1 [Liu, Zhu; Xing, Qiong; Liu, Maili; Tang, Chun] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Hubei, Peoples R China.
[Zhang, Wei-Ping] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310003, Zhejiang, Peoples R China.
[Ren, Xuefeng] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Tang, C (reprint author), Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Hubei, Peoples R China.
EM tanglab@wipm.ac.cn
RI Liu, Maili/A-8543-2011
FU Ministry of Science and Technology of China [2009CB918600]; Chinese
Academy of Sciences [KJCX2-EW-W05]; National Natural Sciences Foundation
of China [21073230]
FX Funding from the Ministry of Science and Technology of China
(2009CB918600 to M. L.), the Chinese Academy of Sciences (KJCX2-EW-W05
to C. T.), and the National Natural Sciences Foundation of China
(21073230 to C. T.) is acknowledged. We thank Christian Griesinger and
G. Marius Clore for advice, and Yong Duan for careful reading of the
manuscript.
NR 37
TC 27
Z9 30
U1 1
U2 38
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1433-7851
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PY 2012
VL 51
IS 2
BP 469
EP 472
DI 10.1002/anie.201106190
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 872ER
UT WOS:000298792100023
PM 22109817
ER
PT J
AU Royak-Schaler, R
Pelser, C
Langenberg, P
Hayes, J
Gardner, L
Nesbitt, K
Citron, W
Drogula, CL
Dwyer, D
AF Royak-Schaler, Renee
Pelser, Colleen
Langenberg, Patricia
Hayes, Jennifer
Gardner, Lisa
Nesbitt, Kim
Citron, Wendla
Drogula, Cynthia L.
Dwyer, Diane
TI Characteristics Associated with the Initiation of Radiation Therapy
after Breast-Conserving Surgery among African American and White Women
Diagnosed with Early-Stage Breast Cancer in Maryland, 2000-2006
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Breast Cancer; Breast-Conserving Surgery; Health Disparities; Radiation
Therapy
ID CARCINOMA IN-SITU; SURGICAL ADJUVANT BREAST; QUALITY-OF-LIFE;
CONSERVATION THERAPY; RACIAL DISPARITIES; UNITED-STATES; PATIENT
COMPLIANCE; PLUS TAMOXIFEN; SOCIAL-CLASS; HEALTH-CARE
AB PURPOSE: Socioeconomic status appears to be an important independent barrier to breast cancer care, irrespective of insurance inequalities. Receiving radiation therapy (RT) reduces local recurrence and mortality in patients receiving breast-conserving surgery (BCS). We investigated racial and socioeconomic determinants of RT initiation after BCS in Maryland.
METHODS: Maryland Cancer Registry breast cancer data for the diagnosis years 2000 through 2006 were analyzed for characteristics associated with receipt of RT after BCS. We used generalized regression models to estimate RT initiation among low-income patients, adjusting for racial, demographic, and clinical covariates.
RESULTS: Low-income women were more likely to be African American; older; uninsured or to use Medicare, Medicaid, or Maryland breast cancer insurance; and have tumors that were estrogen receptor and progesterone-receptor negative. Among low-income women, those at risk of not initiating RT after BCS were more likely to be African American, be older than 80 years of age, and have tumors > 2 cm.
CONCLUSIONS: Socioeconomic disparities were identified in the initiation of RT after BCS in Maryland from 2000 to 2006. In addition, racial disparities in RT after BCS were apparent for women diagnosed from 2000 to 2003. Additional research is needed to investigate uptake of prescribed treatments after BCS and develop strategies for reducing barriers to obtaining treatments among patients at risk for incomplete cancer care. Ann Epidemiol 2012;22:28-36. Published by Elsevier Inc.
C1 [Pelser, Colleen] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Royak-Schaler, Renee; Pelser, Colleen; Langenberg, Patricia; Gardner, Lisa; Nesbitt, Kim] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hayes, Jennifer; Dwyer, Diane] Maryland Dept Hlth & Mental Hyg, Ctr Canc Surveillance & Control, Baltimore, MD USA.
[Citron, Wendla] Univ Maryland, Sch Med, Div Radiat Oncol, Baltimore, MD 21201 USA.
[Drogula, Cynthia L.] Univ Maryland, Div Surg Oncol, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Pelser, C (reprint author), NCI, Canc Prevent Fellowship Program, 6120 Execut Blvd,Room 150E,MSC 7150, Bethesda, MD 20892 USA.
EM colleen.pelser@nih.gov
OI Gardner, Lisa/0000-0003-3340-2818
FU American Cancer Society [RSGT-08-147-01-CPPB]; State of Maryland;
Maryland Cigarette Restitution Fund; Centers for Disease Control and
Prevention (CDC)
FX This study was supported by grant # RSGT-08-147-01-CPPB from the
American Cancer Society. Cancer incidence data were provided by the
Maryland Cancer Registry, Center for Cancer Surveillance and Control,
Department of Health and Mental Hygiene, 201 W. Preston Street, Room
400, Baltimore, MD 21201, http://www.fha.state.md.us/cancer/registry/,
410-767-4055. The State of Maryland, the Maryland Cigarette Restitution
Fund, and the National Program of Cancer Registries (NPCR) of the
Centers for Disease Control and Prevention (CDC) provide the funds that
support the availability of the cancer registry data.
NR 62
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JAN
PY 2012
VL 22
IS 1
BP 28
EP 36
DI 10.1016/j.annepidem.2011.10.001
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 864EZ
UT WOS:000298221100004
PM 22037379
ER
PT J
AU Sung, H
Mendell, NR
AF Sung, Heejong
Mendell, Nancy R.
TI Necessary and Sufficient Conditions for Equality of Sibling and
Parent-Offspring Risk of a Disease Endophenotype in Case Families
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Linkage; sib pair; endophenotype; recurrence risk; additivity
ID LINKAGE ANALYSIS; POWER; PAIRS
AB A large number of linkage and association studies of complex diseases focus on analysis of a more common or more easily measured disease endophenotype. The motivation for this approach is that there is a pleiotropic locus common to both the disease and the endophenotype and that this locus is a major genetic determinant of the endophenotype. In this paper, we determine the conditions under which the risk of the endophenotype in siblings of affected probands with disease equals the risk of the endophenotype in the offspring (parents) of affected parents (offspring) with disease. In doing so we prove that this equality holds if and only if the penetrance of either the endophenotype or the disease (but not necessarily both) is additive.
C1 [Sung, Heejong] Natl Human Genet Res Inst, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Mendell, Nancy R.] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
RP Sung, H (reprint author), Natl Human Genet Res Inst, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
EM sunghe@mail.nih.gov
FU Division of Intramural Research; National Human Genome Research
Institute; National Institutes of Health; National Institute of Mental
Health [R01 44292, 071523]
FX Funding for this project was supported in part by the Division of
Intramural Research, National Human Genome Research Institute, National
Institutes of Health and also part by Division of Extramural Research by
National Institute of Mental Health R01 44292, National Institute of
Mental Health R01 071523. The authors truly appreciate Dr. Steven
Matthysse's suggestions and valuable comments.
NR 8
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JAN
PY 2012
VL 76
BP 86
EP 91
DI 10.1111/j.1469-1809.2011.00685.x
PN 1
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 864QJ
UT WOS:000298254600010
PM 22091704
ER
PT J
AU Kollmannsberger, C
Hirte, H
Siu, LL
Mazurka, J
Chi, K
Elit, L
Walsh, W
Sederias, J
Doyle, A
Eisenhauer, EA
Oza, AM
AF Kollmannsberger, C.
Hirte, H.
Siu, L. L.
Mazurka, J.
Chi, K.
Elit, L.
Walsh, W.
Sederias, J.
Doyle, A.
Eisenhauer, E. A.
Oza, A. M.
TI Temsirolimus in combination with carboplatin and paclitaxel in patients
with advanced solid tumors: a NCIC-CTG, phase I, open-label
dose-escalation study (IND 179)
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE carboplatin; combination; paclitaxel; phase I; temsirolimus
ID GYNECOLOGIC-ONCOLOGY-GROUP; RENAL-CELL CARCINOMA; MAMMALIAN TARGET; MTOR
INHIBITOR; OVARIAN-CARCINOMA; INTERFERON-ALPHA; LUNG-CANCER; III TRIAL;
CCI-779; CHEMOTHERAPY
AB Background: The purpose of the study was to assess the safety, tolerability, recommended phase II dose (RPTD), and preliminary antitumor activity of the combination of carboplatin-paclitaxel (Taxol)-temsirolimus.
Materials and methods: Patients with solid malignancies suitable for carboplatin-paclitaxel (CP) chemotherapy and two or less prior lines of chemotherapy received 15, 20, or 25 mg of temsirolimus per week with CP given every 21 days. Thirty-eight eligible patients were entered into six dose levels with the first two levels administering temsirolimus on days 8 and 15 and the subsequent four dose levels switching to days 1 and 8 temsirolimus administration.
Results: Days 8 and 15 administration of temsirolimus was not feasible due to myelosuppression on day 15. CP on day 1 with temsirolimus on days 1 and 8 was well tolerated. Dose-limiting toxicity (DLT) was grade 4 thrombocytopenia (n = 2) and grade 3 fatigue (n = 1). Relative dose intensities for carboplatin, paclitaxel, and temsirolimus at the RPTD were 92%, 82%, and 56%, respectively. Non-DLT treatment-related adverse events occurring in >20% of patients included fatigue, mucositis, alopecia, neuropathy, nausea, neutropenia, thrombocytopenia, and infection. Grade 3/4 non-hematological toxicity was rare. Partial responses (PRs) and disease stabilization were seen in 46% and 49% of patients, respectively. Nine of 11 (82%) endometrial cancer patients had objective PRs.
Conclusion: Carboplatin-paclitaxel-temsirolimus is well tolerated and the RPTD is carboplatin area under the curve 5 mg/ml/min, paclitaxel 175 mg/m(2), both given on day 1 with temsirolimus 25 mg on days 1 and 8.
C1 [Siu, L. L.; Oza, A. M.] Univ Toronto, Univ Hlth Network, Drug Dev Program, Princess Margaret Hosp, Toronto, ON, Canada.
[Kollmannsberger, C.; Chi, K.] Vancouver Canc Ctr, BC Canc Agcy, Div Med Oncol, Vancouver, BC, Canada.
[Hirte, H.] Juravinski Canc Ctr, Div Med Oncol, Hamilton, ON, Canada.
[Walsh, W.; Sederias, J.; Eisenhauer, E. A.] Queens Univ, Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada.
[Mazurka, J.; Elit, L.] Juravinski Canc Ctr, Div Gynecol Oncol, Hamilton, ON, Canada.
[Doyle, A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Oza, AM (reprint author), Princess Margaret Hosp, Univ Hlth Network, Bras Family Drug Dev Program, 610 Univ Ave,Suite 5-700, Toronto, ON M5G 2M9, Canada.
EM amit.oza@uhn.on.ca
FU Canadian Cancer Society
FX This study was funded by the Canadian Cancer Society through its core
grant support to the NCIC-CTG.
NR 27
TC 17
Z9 17
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JAN
PY 2012
VL 23
IS 1
BP 238
EP 244
DI 10.1093/annonc/mdr063
PG 7
WC Oncology
SC Oncology
GA 866MO
UT WOS:000298385300035
PM 21447615
ER
PT J
AU Linkous, AG
Yazlovitskaya, EM
AF Linkous, Amanda G.
Yazlovitskaya, Eugenia M.
TI Novel Therapeutic Approaches for Targeting Tumor Angiogenesis
SO ANTICANCER RESEARCH
LA English
DT Review
DE VEGF; cPLA2; lysophospholipids; angiogenesis; cancer; review
ID RENAL-CELL CARCINOMA; LYSOPHOSPHATIDIC ACID PRODUCTION; BEVACIZUMAB PLUS
IRINOTECAN; HIGH-GRADE GLIOMAS; ANTIANGIOGENIC THERAPY; OVARIAN-CANCER;
CYTOSOLIC PHOSPHOLIPASE-A2; LYSOPHOSPHOLIPASE-D; RECURRENT GLIOBLASTOMA;
AUTOTAXIN INHIBITORS
AB Current attempts to disrupt the complex process of tumor blood vessel formation are predominantly focused on targeting the vascular endothelial growth factor (VEGF)-VEGFR signaling pathway. Although clinically proven to inhibit VEGF and its receptors, these pharmacologic agents are selective, but not specific. Consequently, many of the approved inhibitors also impair other molecular targets leading to increased toxicity. Current efforts to unravel the complexity of tumor angiogenesis have identified several new candidates for antivascular therapy. In this review article, we identify well-established and novel angiogenic molecules and discuss benefits of the therapeutic approaches based on targeting of such factors.
C1 [Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA.
[Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Linkous, Amanda G.] NIH, Neurooncol Branch, Bethesda, MD 20892 USA.
RP Yazlovitskaya, EM (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, C3210 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA.
EM eugenia.yazlovitskaya@vanderbilt.edu
NR 76
TC 17
Z9 22
U1 0
U2 12
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 JAN
PY 2012
VL 32
IS 1
BP 1
EP 12
PG 12
WC Oncology
SC Oncology
GA 872BH
UT WOS:000298780900001
PM 22213282
ER
PT J
AU Johnson, BC
Metifiot, M
Pommier, Y
Hughes, SH
AF Johnson, Barry C.
Metifiot, Mathieu
Pommier, Yves
Hughes, Stephen H.
TI Molecular Dynamics Approaches Estimate the Binding Energy of HIV-1
Integrase Inhibitors and Correlate with In Vitro Activity
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRAND TRANSFER INHIBITORS;
CARBOXYL-TERMINAL DOMAINS; CATALYTIC DOMAIN; DNA-BINDING; ZINC-BINDING;
VIRAL-DNA; CRYSTAL-STRUCTURE; CROSS-RESISTANCE; RALTEGRAVIR
AB The design of novel integrase (IN) inhibitors has been aided by recent crystal structures revealing the binding mode of these compounds with a full-length prototype foamy virus (PFV) IN and synthetic viral DNA ends. Earlier docking studies relied on incomplete structures and did not include the contribution of the viral DNA to inhibitor binding. Using the structure of PFV IN as the starting point, we generated a model of the corresponding HIV-1 complex and developed a molecular dynamics (MD)-based approach that correlates with the in vitro activities of novel compounds. Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data. Three additional compounds were docked into the IN-DNA complex model and subjected to MD simulations. All three gave interaction potentials within 1 standard deviation of values estimated from the training set, and the most active compound was identified. Additional MD analysis of the raltegravir- and dolutegravir-bound complexes gave internal and interaction energy values that closely match the experimental binding energy of a compound related to raltegravir that has similar activity. These approaches can be used to gain a deeper understanding of the interactions of the inhibitors with the HIV-1 intasome and to identify promising scaffolds for novel integrase inhibitors, in particular, compounds that retain activity against a range of drug-resistant mutants, making it possible to streamline synthesis and testing.
C1 [Johnson, Barry C.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Metifiot, Mathieu; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
EM hughesst@mail.nih.gov
FU NIH, Center for Cancer Research, National Cancer Institute; NIH
FX Our studies were supported by the NIH Intramural Program, Center for
Cancer Research, National Cancer Institute, and by NIH grants from the
AIDS Intramural Targeted Program (IATAP).
NR 56
TC 28
Z9 28
U1 2
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2012
VL 56
IS 1
BP 411
EP 419
DI 10.1128/AAC.05292-11
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 866TB
UT WOS:000298404900049
PM 22037850
ER
PT J
AU Kjellsson, MC
Via, LE
Goh, A
Weiner, D
Low, KM
Kern, S
Pillai, G
Barry, CE
Dartois, V
AF Kjellsson, Maria C.
Via, Laura E.
Goh, Anne
Weiner, Danielle
Low, Kang Min
Kern, Steven
Pillai, Goonaseelan
Barry, Clifton E., III
Dartois, Veronique
TI Pharmacokinetic Evaluation of the Penetration of Antituberculosis Agents
in Rabbit Pulmonary Lesions
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID EPITHELIAL LINING FLUID; MYCOBACTERIUM-TUBERCULOSIS;
CEREBROSPINAL-FLUID; INTRAPULMONARY CONCENTRATIONS; NONREPLICATING
PERSISTENCE; CLINICAL PHARMACOKINETICS; FIBEROPTIC BRONCHOSCOPY; TISSUE
CONCENTRATIONS; MOXIFLOXACIN; MODEL
AB Standard antituberculosis (anti-TB) therapy requires the use of multiple drugs for a minimum of 6 months, with variable outcomes that are influenced by a number of microbiological, pathological, and clinical factors. This is despite the availability of antibiotics that have good activity against Mycobacterium tuberculosis in vitro and favorable pharmacokinetic profiles in plasma. However, little is known about the distribution of widely used antituberculous agents in the pulmonary lesions where the pathogen resides. The rabbit model of TB infection was used to explore the hypothesis that standard drugs have various abilities to penetrate lung tissue and lesions and that adequate drug levels are not consistently reached at the site of infection. Using noncompartmental and population pharmacokinetic approaches, we modeled the rate and extent of distribution of isoniazid, rifampin, pyrazinamide, and moxifloxacin in rabbit lung and lesions. Moxifloxacin reproducibly showed favorable partitioning into lung and granulomas, while the exposure of isoniazid, rifampin, and pyrazinamide in lesions was markedly lower than in plasma. The extent of penetration in lung and lesions followed different trends for each drug. All four agents distributed rapidly from plasma to tissue with equilibration half-lives of less than 1 min to an hour. The models adequately described the plasma concentrations and reasonably captured actual lesion concentrations. Though further refinement is needed to accurately predict the behavior of these drugs in human subjects, our results enable the integration of lesion-specific pharmacokinetic-pharmacodynamic (PK-PD) indices in clinical trial simulations and in in vitro PK-PD studies with M. tuberculosis.
C1 [Goh, Anne; Low, Kang Min; Dartois, Veronique] Novartis Inst Trop Dis, Pharmacol Unit, Singapore, Singapore.
[Kjellsson, Maria C.; Kern, Steven; Pillai, Goonaseelan] Novartis Pharma AG, Modeling & Simulat, Basel, Switzerland.
[Kjellsson, Maria C.] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden.
[Via, Laura E.; Weiner, Danielle; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Dartois, V (reprint author), Novartis Inst Trop Dis, Pharmacol Unit, Singapore, Singapore.
EM veronique.dartois@novartis.com
RI Barry, III, Clifton/H-3839-2012;
OI Kjellsson, Maria/0000-0003-3531-9452; Via, Laura/0000-0001-6074-9521
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; Bill & Melinda Gates (BMGF) Foundation Drug; BMGF
and Wellcome Trust [42808, 37882]
FX This project received funding from the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases, from the Bill & Melinda Gates (BMGF) Foundation
Drug Accelerator program, and the BMGF and Wellcome Trust Grand
Challenges in Global Health initiative (grant numbers 42808 to Joanne
Flynn, University of Pittsburgh, and 37882 to Douglas Young, Imperial
College, London, United Kingdom).
NR 61
TC 67
Z9 67
U1 2
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2012
VL 56
IS 1
BP 446
EP 457
DI 10.1128/AAC.05208-11
PG 12
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 866TB
UT WOS:000298404900053
PM 21986820
ER
PT J
AU Bevilacqua, L
Carli, V
Sarchiapone, M
George, DK
Goldman, D
Roy, A
Enoch, MA
AF Bevilacqua, Laura
Carli, Vladimir
Sarchiapone, Marco
George, Danielle K.
Goldman, David
Roy, Alec
Enoch, Mary-Anne
TI Interaction Between FKBP5 and Childhood Trauma and Risk of Aggressive
Behavior
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID BORDERLINE PERSONALITY-DISORDER; URINARY FREE CORTISOL; EARLY-LIFE
STRESS; DSM-IV; SUICIDAL-BEHAVIOR; BIPOLAR DISORDER; HEALTHY CONTROLS;
SEXUAL-ABUSE; VASOPRESSIN; POLYMORPHISMS
AB Context: Childhood trauma may predispose individuals to aggressive behavior, and both childhood trauma and aggressive behavior are associated with hypothalamic-pituitary-adrenal axis dysregulation.
Objective: To determine whether there would be an interaction between genetic variation in FKBP5 and childhood trauma in predicting aggressive behavior.
Design: Cross-sectional study. Four FKBP5 single-nucleotide polymorphisms used in previous studies (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. Three diplotypes were derived from 2 major putatively functional haplotypes regulating protein expression that were previously associated with glucocorticoid receptor sensitivity.
Setting: Penitentiary District of Abruzzo-Molise in central Italy.
Participants: A population of 583 male Italian prisoners recruited between 2005 and 2008.
Main Outcome Measures: A comprehensive analysis of aggression and impulsivity was undertaken using the Brown-Goodwin Lifetime History of Aggression (BGHA) questionnaire, the Buss-Durkee Hostility Inventory (BDHI), and the Barratt Impulsiveness Scale (BIS). A history of childhood trauma was investigated with the Childhood Trauma Questionnaire. The interaction between the FKBP5 diplotypes and childhood trauma on measures of aggression was analyzed. Analyses were replicated with a second behavioral measure of aggression: violent behavior in jail. Individual single-nucleotide polymorphism analysis was performed.
Results: Childhood trauma had a significant effect on BGHA and BDHI scores but not on BIS scores. We observed a significant influence of the FKBP5 high-expression diplotype on both a lifetime history of aggressive behavior (BGHA) (P=.012) and violent behavior in jail (P=.025) but only in individuals exposed to childhood trauma, in particular to physical abuse. No main effect of the FKBP5 diplotypes was observed.
Conclusion: These data suggest that childhood trauma and variants in the FKBP5 gene may interact to increase the risk of overt aggressive behavior.
C1 [Bevilacqua, Laura; George, Danielle K.; Goldman, David; Enoch, Mary-Anne] NIAAA, LNG, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Carli, Vladimir; Sarchiapone, Marco] Univ Molise, Dept Hlth Sci, Campobasso, Italy.
[Carli, Vladimir] Karolinska Inst, Stockholm, Sweden.
[Roy, Alec] Vet Affairs Med Ctr, Psychiat Serv, E Orange, NJ USA.
RP Bevilacqua, L (reprint author), NIAAA, LNG, Neurogenet Lab, NIH, 5625 Fishers Ln,Room 3S-32, Rockville, MD 20852 USA.
EM laurabevilacqua27@gmail.com
RI Carli, Vladimir/G-4728-2012; Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Sarchiapone,
Marco/0000-0001-9583-3117
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health; National Institute of Drug Abuse, National Institutes of
Health [R01 DA 10336-02]; Pfizer; Lundbeck
FX This research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, and in part by grant R01 DA 10336-02 (Dr Roy) from the
National Institute of Drug Abuse, National Institutes of Health. Dr
Sarchiapone has received financial support from Pfizer and Lundbeck.
NR 62
TC 45
Z9 46
U1 2
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
EI 1538-3636
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JAN
PY 2012
VL 69
IS 1
BP 62
EP 70
PG 9
WC Psychiatry
SC Psychiatry
GA 870NH
UT WOS:000298675700008
PM 22213790
ER
PT J
AU Yeh, S
Fahle, G
Forooghian, F
Faia, LJ
Weichel, ED
Stout, JT
Flaxel, CJ
Lauer, AK
Sen, HN
Nussenblatt, RB
AF Yeh, Steven
Fahle, Gary
Forooghian, Farzin
Faia, Lisa J.
Weichel, Eric D.
Stout, J. Timothy
Flaxel, Christina J.
Lauer, Andreas K.
Sen, H. Nida
Nussenblatt, Robert B.
TI Polymerase Chain Reaction-Based Ganciclovir Resistance Testing of Ocular
Fluids for Cytomegalovirus Retinitis
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Editorial Material
C1 [Sen, H. Nida; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Yeh, Steven] Emory Univ, Sch Med, Retina Serv, Emory Eye Ctr, Atlanta, GA USA.
[Fahle, Gary] Dept Lab Med, Bethesda, MD USA.
[Forooghian, Farzin] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
[Faia, Lisa J.] William Beaumont Hosp, Associated Retinal Consultants, Royal Oak, MI 48072 USA.
[Weichel, Eric D.] Retina Grp Washington, Washington, DC USA.
[Stout, J. Timothy; Flaxel, Christina J.; Lauer, Andreas K.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
RP Nussenblatt, RB (reprint author), NEI, NIH, Bldg 10,10N-112, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU NEI NIH HHS [P30 EY010572]
NR 8
TC 6
Z9 6
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JAN
PY 2012
VL 130
IS 1
BP 113
EP 115
PG 3
WC Ophthalmology
SC Ophthalmology
GA 874LE
UT WOS:000298957900015
PM 22232481
ER
PT J
AU Qu, AJ
Shah, YM
Manna, SK
Gonzalez, FJ
AF Qu, Aijuan
Shah, Yatrik M.
Manna, Soumen K.
Gonzalez, Frank J.
TI Disruption of Endothelial Peroxisome Proliferator-Activated Receptor
gamma Accelerates Diet-Induced Atherogenesis in LDL Receptor-Null Mice
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE atherosclerosis; endothelial function; hypertension; lipids;
lipoproteins
ID LOW-DENSITY-LIPOPROTEIN; BONE-MARROW-TRANSPLANTATION;
SMOOTH-MUSCLE-CELLS; PPAR-GAMMA; DEFICIENT MICE; CHOLESTEROL EFFLUX;
SIGNALING PATHWAY; BLOOD-VESSELS; ATHEROSCLEROSIS; EXPRESSION
AB Objective-Peroxisome proliferator-activated receptor gamma (PPAR gamma) is widely expressed in vessel walls, and it's activation by agonists showed beneficial effects in cardiovascular diseases. However, the role of endothelial cell (EC) PPAR gamma in atherogenesis is not fully understood.
Methods and Results-To assess the contribution of endothelial-specific PPAR gamma in atherosclerosis, EC-specific PPAR gamma disruption and LDL receptor (LDLR) double-knockout (PPAR gamma(Delta EC)/LDLR(-/-)) mice were developed. When challenged with a high-cholesterol diet for 4 weeks, PPAR gamma(Delta EC)/LDLR(-/-) mice exhibited severe atherosclerotic lesions compared to either their littermate controls or macrophage-specific PPAR gamma disruption and LDLR double knockout (PPAR gamma(Delta M Phi)/LDLR(-/-)) mice. Metabolic analysis showed severe dyslipidemia and significant increase in systolic blood pressure in the PPAR gamma(Delta EC)/LDLR(-/-) mice. Histological analysis and real-time quantitative PCR suggested an exacerbated inflammation in PPAR gamma(Delta EC)/LDLR(-/-) mice, as revealed by the increases of proinflammatory gene expression and macrophage infiltration in vivo and in vitro. Furthermore, in vivo endothelial permeability was also increased by endothelial PPAR gamma disruption. Bone-marrow transplantation studies, which reconstituted hematopoietic PPAR gamma, demonstrated that the accelerated atherogenesis was due to endothelial PPAR gamma deficiency.
Conclusion-Endothelial PPAR gamma plays an important protective role in atherogenesis. (Arterioscler Thromb Vasc Biol. 2012;32:65-73.)
C1 [Qu, Aijuan; Shah, Yatrik M.; Manna, Soumen K.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
[Shah, Yatrik M.] Univ Michigan, Sch Med, Div Gastroenterol, Dept Mol & Integrat Physiol & Internal Med, Ann Arbor, MI USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20814 USA.
EM gonzalef@mail.nih.gov
FU National Cancer Institute; National Institutes of Health [CA148828]
FX This work was supported by the National Cancer Institute Intramural
Research Program and National Institutes of Health Grant CA148828 (to
Y.M.S.).
NR 41
TC 17
Z9 17
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JAN
PY 2012
VL 32
IS 1
BP 65
EP U178
DI 10.1161/ATVBAHA.111.239137
PG 14
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 865CP
UT WOS:000298288700011
PM 22015658
ER
PT J
AU Conroy, MB
Kwoh, CK
Krishnan, E
Nevitt, MC
Boudreau, R
Carbone, LD
Chen, HP
Harris, TB
Newman, AB
Goodpaster, BH
AF Conroy, Molly B.
Kwoh, C. Kent
Krishnan, Eswar
Nevitt, Michael C.
Boudreau, Robert
Carbone, Laura D.
Chen, Hepei
Harris, Tamara B.
Newman, Anne B.
Goodpaster, Bret H.
CA Hlth ABC Study
TI Muscle strength, mass, and quality in older men and women with knee
osteoarthritis
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID QUADRICEPS STRENGTH; COMPUTED-TOMOGRAPHY; SKELETAL-MUSCLE; HEALTH;
ATTENUATION; EXERCISE
AB Objective To examine the relationship between knee osteoarthritis (OA) and muscle parameters in a biracial cohort of older adults.
Methods. Participants in the Health, Aging and Body Composition Study (n = 858) were included in this cross-sectional analysis. Computed tomography was used to measure muscle area, and quadriceps strength was measured isokinetically. Muscle quality (specific torque) was defined as strength per unit of muscle area for both the entire thigh and quadriceps. Knee OA was assessed based on radiographic features and knee pain. We compared muscle parameters between those with and without radiographic knee OA (+RKOA group and -RKOA group, respectively) and among 4 groups defined by +RKOA and -RKOA with and without pain.
Results. The mean +/- SD age was 73.5 +/- 2.9 years and the mean +/- SD body mass index (BMI) was 27.9 +/- 4.8 kg/m(2). Fifty-eight percent of participants were women and 44% were African American. Compared to the +RKOA participants, -RKOA participants had a higher BMI (30.2 versus 26.8 kg/m(2)), larger thigh muscles (117.9 versus 108.9 cm(2)), and a greater amount of intermuscular fat (12.5 versus 9.9 cm(2); all P < 0.0001). In adjusted models, the +RKOA participants had significantly lower specific torque (P < 0.001), indicating poorer muscle quality, than +RKOA participants, but there was no difference between groups in quadriceps specific torque. The +RKOA without pain (P < 0.05) and the +RKOA with pain (P < 0.001) participants had lower specific torque compared to the -RKOA without pain group. There were no significant differences in quadriceps specific torque among groups.
Conclusion. Muscle quality was significantly poorer in participants with RKOA regardless of pain status. Future studies should address how lifestyle interventions might affect muscle quality and progression of knee OA.
C1 [Conroy, Molly B.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA.
[Krishnan, Eswar] Stanford Univ, Palo Alto, CA 94304 USA.
[Nevitt, Michael C.] Prevent Sci Grp, San Francisco, CA USA.
[Carbone, Laura D.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Carbone, Laura D.] Dept Vet Affairs Med Ctr, Memphis, TN USA.
[Chen, Hepei] Covance Labs, Chantilly, VA USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RP Conroy, MB (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM conroymb@upmc.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
[R01-NR012459]; NIH, National Institute on Aging; NIH [K23-HL-085405]
FX Supported by the National Institute on Aging (contracts N01-AG-6-2101,
N01-AG-6-2103, and N01-AG-6-2106, and grant R01-AG028050) and the
National Institute of Nursing Research (grant R01-NR012459) and
partially supported by the Intramural Research program of the NIH,
National Institute on Aging. Dr. Conroy's work was supported by a career
development award from the NIH (K23-HL-085405).
NR 21
TC 27
Z9 28
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JAN
PY 2012
VL 64
IS 1
BP 15
EP 21
DI 10.1002/acr.20588
PG 7
WC Rheumatology
SC Rheumatology
GA 868QB
UT WOS:000298536700004
PM 22213722
ER
PT J
AU Cheng, S
Wang, N
Larson, MG
Palmisano, JN
Mitchell, GF
Benjamin, EJ
Vasan, RS
Levy, D
McCabe, EL
Vita, JA
Wang, TJ
Shaw, SY
Cohen, KS
Hamburg, NM
AF Cheng, Susan
Wang, Na
Larson, Martin G.
Palmisano, Joseph N.
Mitchell, Gary F.
Benjamin, Emelia J.
Vasan, Ramachandran S.
Levy, Daniel
McCabe, Elizabeth L.
Vita, Joseph A.
Wang, Thomas J.
Shaw, Stanley Y.
Cohen, Kenneth S.
Hamburg, Naomi M.
TI Circulating angiogenic cell populations, vascular function, and arterial
stiffness
SO ATHEROSCLEROSIS
LA English
DT Article
DE Angiogenesis; Vascular function; Risk factors; Endothelium; Epidemiology
ID ENDOTHELIAL PROGENITOR CELLS; CORONARY-HEART-DISEASE;
COLONY-FORMING-UNITS; BONE-MARROW; CARDIOVASCULAR RISK;
MONONUCLEAR-CELLS; AORTIC STIFFNESS; ADVANCING AGE; DYSFUNCTION; NUMBER
AB Objective: Several bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness.
Methods: We studied 1948 Framingham Heart Study participants (mean age, 66 +/- 9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing.
Results: In unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (beta = -0.052 +/- 0.011, P < 0.001 and beta = -0.030 +/- 0.011, P = 0.008, respectively) and with higher carotid-brachial pulse wave velocity (beta = 0.144 +/- 0.043, P = 0.001 and beta = 0.112 +/- 0.043, P = 0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (beta = -0.229 +/- 0.094, P = 0.015). However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness.
Conclusions: In our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Hamburg, Naomi M.] Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Cheng, Susan; Larson, Martin G.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Levy, Daniel; Wang, Thomas J.; Hamburg, Naomi M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
[Wang, Na; Palmisano, Joseph N.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Wang, Na; Palmisano, Joseph N.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[McCabe, Elizabeth L.; Wang, Thomas J.; Shaw, Stanley Y.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Cohen, Kenneth S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA.
RP Hamburg, NM (reprint author), Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, 88 E Newton St C818, Boston, MA 02118 USA.
EM naomi.hamburg@bmc.org
OI Benjamin, Emelia/0000-0003-4076-2336; Hamburg,
Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Larson,
Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970
FU NIH/NHLBI [N01-HC25195]; NIH [1R01HL60040, 1R01HL70100, R01AG028321,
HL083197, HL083781, HL102299]; Ellison Foundation; Itamar Medical
FX The Framingham Heart Study is funded by NIH/NHLBI contract N01-HC25195.
The project was supported NIH grants 1R01HL60040 (EJB), 1R01HL70100
(EJB), R01AG028321 (EJB), and HL083197 (TJW). Dr. Hamburg is supported
by NIH grants HL083781 and HL102299. Dr. Cheng is supported by a grant
from the Ellison Foundation. The work was supported by an unrestricted
research grant to Dr. Benjamin from Itamar Medical. The grant was used
to conduct statistical analyses following guidelines established by the
National Heart, Lung, and Blood Institute:
http://www.nhlbi.nih.gov/funding/policies/thirdparty.htm.
NR 36
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JAN
PY 2012
VL 220
IS 1
BP 145
EP 150
DI 10.1016/j.atherosclerosis.2011.10.015
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866IU
UT WOS:000298374800024
PM 22093724
ER
PT J
AU Martinowich, K
Schloesser, RJ
Lu, Y
Jimenez, DV
Paredes, D
Greene, JS
Greig, NH
Manji, HK
Lu, B
AF Martinowich, Keri
Schloesser, Robert J.
Lu, Yuan
Jimenez, Dennisse V.
Paredes, Daniel
Greene, Joshua S.
Greig, Nigel H.
Manji, Husseini K.
Lu, Bai
TI Roles of p75(NTR), Long-Term Depression, and Cholinergic Transmission in
Anxiety and Acute Stress Coping
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Anxiety; basal forebrain; hippocampus; long-term depression;
neurotrophin; p75(NTR)
ID P75 NEUROTROPHIN RECEPTOR; BLACK-WHITE BOX; TYROSINE PHOSPHORYLATION;
HIPPOCAMPAL NEUROGENESIS; SYNAPTIC PLASTICITY; FOS EXPRESSION; SPATIAL
MEMORY; KNOCKOUT MICE; ANIMAL-MODEL; LTD
AB Background: Stress is causally associated with anxiety. Although the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons have been implicated in stress response. p75(NTR) is a panneurotrophin receptor expressed almost exclusively in basal forebrain cholinergic neurons in adult brain. This study investigated whether and how p75(NTR), via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors.
Methods: We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis, and neuronal activity mapping to assess the role of p75(NTR) in mood and stress-related behaviors and its underlying cellular and molecular mechanisms.
Results: We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice but not in mice lacking p75(NTR). The p75(NTR) mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75(NTR) perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75(NTR) deletion.
Conclusions: Our results suggest that loss of p75(NTR) leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety.
C1 [Martinowich, Keri; Schloesser, Robert J.; Jimenez, Dennisse V.; Manji, Husseini K.] Natl Inst Neurol Disorders & Stroke, Mood & Anxiety Disorders Program, NIMH, Bethesda, MD USA.
[Martinowich, Keri; Lu, Yuan; Greene, Joshua S.; Lu, Bai] Natl Inst Neurol Disorders & Stroke, Genes Cognit & Psychosis Program, NIMH, Bethesda, MD USA.
[Paredes, Daniel] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, Bethesda, MD USA.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Baltimore, MD 21224 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Lu, B (reprint author), Glaxo SmithKline, R&D China, Biol, Bldg 3,898 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China.
EM bai.b.lu@gsk.com
RI Paredes , Daniel/L-6610-2013; Martinowich, Keri/F-9841-2012;
OI Martinowich, Keri/0000-0002-5237-0789
FU National Institute of Mental Health; National Alliance for Research on
Schizophrenia and Depression
FX This work was supported by the National Institute of Mental Health
Intramural Program. KM and RJS are supported by National Alliance for
Research on Schizophrenia and Depression Young Investigator Awards.
NR 46
TC 18
Z9 18
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 1
PY 2012
VL 71
IS 1
BP 75
EP 83
DI 10.1016/j.biopsych.2011.08.014
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 863BI
UT WOS:000298137400014
PM 21978521
ER
PT J
AU Shi, GB
Shaw, G
Liang, YH
Subburaman, P
Li, Y
Wu, Y
Yan, HG
Ji, XH
AF Shi, Genbin
Shaw, Gary
Liang, Yu-He
Subburaman, Priadarsini
Li, Yue
Wu, Yan
Yan, Honggao
Ji, Xinhua
TI Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin
pyrophosphokinase: New design with improved properties
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Antibacterial; Bisubstrate; Folate; HPPK; Pterin
ID ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; ARGININE RESIDUE-82;
CRYSTAL-STRUCTURE; TERNARY COMPLEX; NMR; CRYSTALLOGRAPHY; BIOSYNTHESIS;
SOFTWARE; BINDING
AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. The enzyme is essential for microorganisms, is absent from humans, and is not the target for any existing antibiotics. Therefore, HPPK is an attractive target for developing novel antimicrobial agents. Previously, we characterized the reaction trajectory of HPPK-catalyzed pyrophosphoryl transfer and synthesized a series of bisubstrate analog inhibitors of the enzyme by linking 6-hydroxymethylpterin to adenosine through 2, 3, or 4 phosphate groups. Here, we report a new generation of bisubstrate analog inhibitors. To improve protein binding and linker properties of such inhibitors, we have replaced the pterin moiety with 7,7-dimethyl-7,8-dihydropterin and the phosphate bridge with a piperidine linked thioether. We have synthesized the new inhibitors, measured their K-d and IC50 values, determined their crystal structures in complex with HPPK, and established their structure-activity relationship. 6-Carboxylic acid ethyl ester-7,7-dimethyl-7,8-dihydropterin, a novel intermediate that we developed recently for easy derivatization at position 6 of 7,7-dimethyl-7,8-dihydropterin, offers a much high yield for the synthesis of bisubstrate analogs than that of previously established procedure. Published by Elsevier Ltd.
C1 [Shi, Genbin; Shaw, Gary; Liang, Yu-He; Subburaman, Priadarsini; Ji, Xinhua] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Li, Yue; Wu, Yan; Yan, Honggao] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA.
RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM jix@mail.nih.gov
RI Ji, Xinhua/C-9664-2012; LIANG, YUHE/B-6704-2012
OI Ji, Xinhua/0000-0001-6942-1514;
FU NIH [GM51901]; NIAID NIH/FDA [Y3-RC-8007-01]; NIH, National Cancer
Institute, Center for Cancer Research
FX This research was supported by NIH Grant GM51901 (H.Y.), NIAID Trans
NIH/FDA Intramural Biodefense Program Y3-RC-8007-01 (X.J.), and the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. Mass spectrometry experiments were conducted
on an Agilent 1100 series LC/Mass Selective Detector maintained by the
Biophysics Resource in the Structural Biophysics Laboratory, an Agilent
1200 LC/MSD-SL system in the Chemical Biology Laboratory, and a
Thermoquest Surveyor Finnigan LCQ deca maintained by the Comparative
Carcinogenesis Laboratory of National Cancer Institute at Frederick.
X-ray diffraction data were collected at the Southeast Regional
Collaborative Access Team (SER-CAT) 22-ID and 22-BM beamlines at the
Advanced Photon Source (APS), Argonne National Laboratory (ANL).
NR 51
TC 7
Z9 7
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JAN 1
PY 2012
VL 20
IS 1
BP 47
EP 57
DI 10.1016/j.bmc.2011.11.032
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 869XO
UT WOS:000298633300005
PM 22169600
ER
PT J
AU Kim, YS
Kil, MJ
Kang, SU
Ryu, H
Kim, MS
Cho, Y
Bhondwe, RS
Thorat, SA
Sun, W
Liu, KL
Lee, JH
Choi, S
Pearce, LV
Pavlyukovets, VA
Morgan, MA
Tran, R
Lazar, J
Blumberg, PM
Lee, J
AF Kim, Yong Soo
Kil, Min-Jung
Kang, Sang-Uk
Ryu, HyungChul
Kim, Myeong Seop
Cho, Yongsung
Bhondwe, Rahul S.
Thorat, Shivaji A.
Sun, Wei
Liu, Keliang
Lee, Jin Hee
Choi, Sun
Pearce, Larry V.
Pavlyukovets, Vladimir A.
Morgan, Matthew A.
Tran, Richard
Lazar, Jozsef
Blumberg, Peter M.
Lee, Jeewoo
TI N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1
antagonists: Structure-activity relationships in the A-region
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE TRPV1 antagonists; Analgesic; Molecular modeling; Capsaicin;
Resiniferatoxin
ID VANILLOID RECEPTOR; CAPSAICIN RECEPTORS; AGONISTS; CHANNEL; ANALOGS;
POTENT
AB Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Kim, Yong Soo; Kil, Min-Jung; Kang, Sang-Uk; Ryu, HyungChul; Kim, Myeong Seop; Cho, Yongsung; Bhondwe, Rahul S.; Thorat, Shivaji A.; Lee, Jeewoo] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
[Sun, Wei; Liu, Keliang] Shenyang Pharmaceut Univ, Shenyang 110016, Liaoning, Peoples R China.
[Lee, Jin Hee; Choi, Sun] Ewha Womans Univ, Div Life & Pharmaceut Sci, Coll Pharm, Seoul 120750, South Korea.
[Lee, Jin Hee; Choi, Sun] Ewha Womans Univ, Natl Core Res Ctr Cell Signaling & Drug Discovery, Seoul 120750, South Korea.
[Pearce, Larry V.; Pavlyukovets, Vladimir A.; Morgan, Matthew A.; Tran, Richard; Lazar, Jozsef; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU Digital-biotech; National Research Foundation of Korea (NRF)
[R11-2007-107-02001-0]; National Core Research Center (NCRC) of MEST
[2011-0006244]; NRF through Center for Cell Signaling & Drug Discovery
Research at Ewha Womans University; National Institutes of Health,
Center for Cancer Research, National Cancer Institute [Z1A BC 005270]
FX This research was supported by Research Funding from Digital-biotech,
Grants R11-2007-107-02001-0 from the National Research Foundation of
Korea (NRF), the National Core Research Center (NCRC) program (No.
2011-0006244) of MEST and NRF through the Center for Cell Signaling &
Drug Discovery Research at Ewha Womans University, and the intramural
program of the National Institutes of Health, Center for Cancer
Research, National Cancer Institute (project Z1A BC 005270).
NR 20
TC 11
Z9 11
U1 0
U2 5
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 JAN 1
PY 2012
VL 20
IS 1
BP 215
EP 224
DI 10.1016/j.bmc.2011.11.008
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 869XO
UT WOS:000298633300022
PM 22169633
ER
PT J
AU Sundaram, R
McLain, AC
Louis, GMB
AF Sundaram, Rajeshwari
McLain, Alexander C.
Louis, Germaine M. Buck
TI A survival analysis approach to modeling human fecundity
SO BIOSTATISTICS
LA English
DT Article
DE Censoring; Conception; Discrete survival; Fecundity; Random effects;
Time-varying covariates
ID MENSTRUAL-CYCLE; PREGNANCY; CONCEPTION; TIME; FECUNDABILITY;
PROBABILITIES; FREQUENCY; VIABILITY
AB Understanding conception probabilities is important not only for helping couples to achieve pregnancy but also in identifying acute or chronic reproductive toxicants that affect the highly timed and interrelated processes underlying hormonal profiles, ovulation, libido, and conception during menstrual cycles. Currently, 2 statistical approaches are available for estimating conception probabilities depending upon the research question and extent of data collection during the menstrual cycle: a survival approach when interested in modeling time-to-pregnancy (TTP) in relation to women or couples' purported exposure(s), or a hierarchical Bayesian approach when one is interested in modeling day-specific conception probabilities during the estimated fertile window. We propose a biologically valid discrete survival model that unifies the above 2 approaches while relaxing some assumptions that may not be consistent with human reproduction or behavior. This approach combines both the survival and the hierarchical models allowing investigators to obtain the distribution of TTP and day-specific probabilities during the fertile window in a single model. Our model allows for the consideration of covariate effects at both the cycle and the daily level while accounting for daily variation in conception. We conduct extensive simulations and utilize the New York State Angler Prospective Pregnancy Cohort Study to illustrate our approach. We also provide the code to implement the model in R software in the supplemental section of the supplementary material available at Biostatistics online.
C1 [Sundaram, Rajeshwari; McLain, Alexander C.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
RP Sundaram, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM sundaramr2@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX Intramural Research Program of the National Institutes of Health; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 26
TC 10
Z9 10
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2012
VL 13
IS 1
BP 4
EP 17
DI 10.1093/biostatistics/kxr015
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 863TZ
UT WOS:000298192300002
PM 21697247
ER
PT J
AU Zhang, B
Chen, Z
Albert, PS
AF Zhang, Bo
Chen, Zhen
Albert, Paul S.
TI Latent class models for joint analysis of disease prevalence and
high-dimensional semicontinuous biomarker data
SO BIOSTATISTICS
LA English
DT Article
DE Categorical data; Chemical exposure biomarkers; Latent variables; Monte
Carlo EM algorithm; Random effects
ID EM ALGORITHM; MAXIMUM-LIKELIHOOD; LONGITUDINAL DATA; ENDOMETRIOSIS;
REGRESSION; MIXTURES
AB High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exposure data, including a large number of biomarkers, numerous zero values, and complex mean-variance relationship in the biomarkers levels. A Monte Carlo EM (MCEM) algorithm is proposed for parameter estimation. Both the MCEM algorithm and model selection procedures are shown to work well in simulations and applications. In applying the proposed approach to an epidemiological study that examined the relationship between environmental polychlorinated biphenyl (PCB) exposure and the risk of endometriosis, we identified a highly significant overall effect of PCB concentrations on the risk of endometriosis.
C1 [Zhang, Bo; Chen, Zhen; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
RP Zhang, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
EM bo.zhang@nih.gov
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Institute of
Environmental Health Sciences [1R01ES09044-01]
FX Intramural Research Program of the National Institutes of Health; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Environmental Health Sciences (Grant
1R01ES09044-01).
NR 18
TC 2
Z9 2
U1 7
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2012
VL 13
IS 1
BP 74
EP 88
DI 10.1093/biostatistics/kxr024
PG 15
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 863TZ
UT WOS:000298192300007
PM 21908867
ER
PT J
AU Moore, HM
AF Moore, H. M.
TI The NCI Biospecimen Research Network
SO BIOTECHNIC & HISTOCHEMISTRY
LA English
DT Article
DE best practices; biobank; biospecimen; cancer; human; quality; research
ID QUALITY; CANCER; TISSUE
AB High quality cancer research using human biospecimens must be based on biospecimens that have been obtained according to rigorous ethical and procedural standards. Methods for biospecimen collection, stabilization, processing and storage for research, however, are highly variable and the biospecimens available for research often are of unknown quality. The National Cancer Institute Biospecimen Research Network program was initiated in 2006 to conduct, sponsor, report and collaborate on research to better understand the effects of different biospecimen collection methods on downstream molecular analysis. An online Biospecimen Research Database and an annual symposium, Advancing Cancer Research through Biospecimen Science, have been developed and many research projects are underway to develop a knowledge base from which to develop evidence-based biospecimen standard operating procedures and methods for assessing biospecimen quality. These efforts will enable better cancer research and development efforts.
C1 [Moore, H. M.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA.
RP Moore, HM (reprint author), NCI, Off Biorepositories & Biospecimen Res, 11400 Rockville Pike,Suite 700, Bethesda, MD 20852 USA.
EM moorehe@mail.nih.gov
NR 14
TC 8
Z9 8
U1 0
U2 3
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1052-0295
J9 BIOTECH HISTOCHEM
JI Biotech. Histochem.
PD JAN
PY 2012
VL 87
IS 1
BP 18
EP 23
DI 10.3109/10520295.2011.591833
PG 6
WC Biotechnology & Applied Microbiology; Cell Biology
SC Biotechnology & Applied Microbiology; Cell Biology
GA 874UA
UT WOS:000298982400005
PM 21745162
ER
PT J
AU Malicdan, MCV
Nishino, I
AF Malicdan, May Christine V.
Nishino, Ichizo
TI Autophagy in Lysosomal Myopathies
SO BRAIN PATHOLOGY
LA English
DT Article
DE autophagy; Danon disease; LAMP-2; lysosome; myopathy; Pompe disease
ID CHAPERONE-MEDIATED AUTOPHAGY; GLYCOGEN-STORAGE-DISEASE; ACID
ALPHA-GLUCOSIDASE; POMPE-DISEASE; DANON-DISEASE; VACUOLAR MYOPATHY;
OXIDATIVE STRESS; SKELETAL-MUSCLE; DISTAL MYOPATHY; LATE-ONSET
AB Lysosomal myopathies are hereditary myopathies characterized morphologically by the presence of autophagic vacuoles. In mammals, autophagy plays an important role for the turnover of cellular components, particularly in response to starvation or glucagons. In normal muscle, autolysosomes or autophagosomes are typically inconspicuous. In distinct neuromuscular disorders, however, lysosomes become structurally abnormal and functionally impaired, leading to the accumulation of autophagic vacuoles in myofibers. In some instances, the accumulation of autophagic vacuoles can be a prominent feature, implicating autophagy as a contributor to disease pathomechanism and/or progression. At present, there are two disorders in the muscle that are associated with a primary defect in lysosomal proteins, namely Pompe disease and Danon disease. This review will give a brief discussion on these disorders, highlighting the role of autophagy in disease progression.
C1 [Malicdan, May Christine V.; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo 1870031, Japan.
[Malicdan, May Christine V.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Nishino, I (reprint author), 4-1-1 Ogawahigashi Cho, Kodaira, Tokyo 1878502, Japan.
EM nishino@ncnp.go.jp
RI Malicdan, May Christine/F-2806-2013;
OI Nishino, Ichizo/0000-0001-9452-112X
NR 52
TC 33
Z9 34
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1015-6305
J9 BRAIN PATHOL
JI Brain Pathol.
PD JAN
PY 2012
VL 22
IS 1
BP 82
EP 88
DI 10.1111/j.1750-3639.2011.00543.x
PG 7
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 860CL
UT WOS:000297924900010
PM 22150923
ER
PT J
AU Falk, RT
Gentzschein, E
Stanczyk, FZ
Garcia-Closas, M
Figueroa, JD
Ioffe, OB
Lissowska, J
Brinton, LA
Sherman, ME
AF Falk, Roni T.
Gentzschein, Elisabet
Stanczyk, Frank Z.
Garcia-Closas, Montserrat
Figueroa, Jonine D.
Ioffe, Olga B.
Lissowska, Jolanta
Brinton, Louise A.
Sherman, Mark E.
TI Sex steroid hormone levels in breast adipose tissue and serum in
postmenopausal women
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Sex steroid hormone; Breast adipose; Breast cancer; Intratissue; Hormone
receptor
ID CANCER RISK; AROMATASE EXPRESSION; RECEPTOR STATUS; MAMMARY-GLAND;
ESTROGEN; DEHYDROEPIANDROSTERONE; INFLAMMATION; ANDROGENS; SULFATASE
AB Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. We used a previously validated method to measure levels of estrone, estradiol, androstenedione, and testosterone in adipose tissue removed as part of breast excisions performed for cancer in 100 postmenopausal women (69 ER/PR +/+ and 31 ER/PR -/-) participating in a breast cancer case-control study. We also measured the same steroid hormones, as well as estrone sulfate, and sex hormone-binding globulin (SHBG) in serum from these patients and 100 controls matched on ages at blood collection and on menopause. Overall, concentrations of serum hormones did not vary significantly between controls and cases. However, women with ER-/PR- breast cancers had lower circulating levels of all measured sex steroid hormones and higher SHBG levels than women with ER+/PR+ breast cancers and controls. Similarly, hormone concentrations in breast adipose tissue were higher among women with ER+/PR+ compared to ER-/PR- breast cancer, although differences were only significant for testosterone. These data demonstrate that high sex steroid concentrations in both serum and adipose tissues are more strongly related to ER+/PR+ than ER-/PR- breast cancers. Measurement of sex hormones in serum and in the microenvironment may help in understanding the hormonal etiology of breast cancer, suggest methods for prevention, and have value in gauging treatment response and prognosis.
C1 [Falk, Roni T.; Garcia-Closas, Montserrat; Figueroa, Jonine D.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA.
[Gentzschein, Elisabet; Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Ioffe, Olga B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
RP Falk, RT (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA.
EM falkr@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799
FU Intramural NIH HHS [ZIA CP010126-18]
NR 39
TC 17
Z9 17
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JAN
PY 2012
VL 131
IS 1
BP 287
EP 294
DI 10.1007/s10549-011-1734-5
PG 8
WC Oncology
SC Oncology
GA 861GB
UT WOS:000298006300029
PM 21870130
ER
PT J
AU Tewari, P
Ryan, AW
Hayden, PJ
Catherwood, M
Drain, S
Staines, A
Grant, T
Nieters, A
Becker, N
de Sanjose, S
Foretova, L
Maynardie, M
Cocco, P
Boffetta, P
Brennan, P
Chanock, S
Lawler, M
Browne, PV
AF Tewari, Prerna
Ryan, Anthony W.
Hayden, Patrick J.
Catherwood, Mark
Drain, Stephen
Staines, Anthony
Grant, Tim
Nieters, Alexandra
Becker, Nikolaus
de Sanjose, Silvia
Foretova, Lenka
Maynardie, Mark
Cocco, Pierluigi
Boffetta, Paolo
Brennan, Paul
Chanock, Stephen
Lawler, Mark
Browne, Paul V.
TI Genetic variation at the 8q24 locus confers risk to multiple myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE multiple myeloma; germline variation; susceptibility; single nucleotide
polymorphisms; aetiology
ID GENOME-WIDE ASSOCIATION; CANCER
C1 [Tewari, Prerna; Lawler, Mark; Browne, Paul V.] Trinity Coll Dublin, Durkan Leukaemia Labs, Dept Haematol, Dublin, Ireland.
[Ryan, Anthony W.] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland.
[Hayden, Patrick J.; Browne, Paul V.] St James Hosp, Dept Haematol, Dublin 8, Ireland.
[Catherwood, Mark; Drain, Stephen] Belfast City Hosp, Dept Haematol, Belfast BT9 7AD, Antrim, North Ireland.
[Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland.
[Grant, Tim] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland.
[Nieters, Alexandra; Becker, Nikolaus] German Canc Res Ctr, D-6900 Heidelberg, Germany.
[de Sanjose, Silvia] Catalan Inst Oncol, Barcelona, Spain.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Maynardie, Mark] Registre Hemopathies Malignes Cote dOr, Dijon, France.
[Cocco, Pierluigi] Univ Cagliari, Inst Occupat Med, Cagliari, Italy.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Chanock, Stephen] Natl Canc Inst Gaithersburg, Core Genotyping Facil, Adv Technol Corp, Gaithersburg, MA USA.
RP Tewari, P (reprint author), Trinity Coll Dublin, Durkan Leukaemia Labs, Dept Haematol, Dublin, Ireland.
EM tewarip@tcd.ie
RI Ryan, Anthony/A-1336-2010; de Sanjose Llongueras, Silvia/H-6339-2014;
OI Ryan, Anthony/0000-0001-5005-3344; Staines, Anthony/0000-0001-9161-1357;
Browne, Paul/0000-0001-5310-1487
NR 9
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JAN
PY 2012
VL 156
IS 1
BP 133
EP 137
DI 10.1111/j.1365-2141.2011.08798.x
PG 6
WC Hematology
SC Hematology
GA 861YX
UT WOS:000298058100015
PM 21770920
ER
PT J
AU Chen, SH
Wu, HM
Ossola, B
Schendzielorz, N
Wilson, BC
Chu, CH
Chen, SL
Wang, Q
Zhang, D
Qian, L
Li, X
Hong, JS
Lu, RB
AF Chen, S. H.
Wu, H. M.
Ossola, B.
Schendzielorz, N.
Wilson, B. C.
Chu, C. H.
Chen, S. L.
Wang, Q.
Zhang, D.
Qian, L.
Li, X.
Hong, J. S.
Lu, R. B.
TI Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor,
protects dopaminergic neurons from neurotoxin-induced damage
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE SAHA; neuroprotection; neurodegenerative disease; HDAC; neurotrophic
factors; Parkinson's disease
ID NEUROTROPHIC FACTOR GDNF; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE;
NERVOUS-SYSTEM; IN-VITRO; MICROGLIA; NEURODEGENERATION; BRAIN; CELLS;
DEGENERATION
AB BACKGROUND AND PURPOSE
Prevention or disease-modifying therapies are critical for the treatment of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. However, no such intervention is currently available. Growing evidence has demonstrated that administration of histone deacetylase (HDAC) inhibitors ameliorates a wide range of neurologic and psychiatric disorders in experimental models. Suberoylanilide hydroxamic acid (SAHA) was the first HDAC inhibitor approved by the Food and Drug Administration for the sole use of cancer therapy. The purpose of this study was to explore the potential new indications of SAHA for therapy of neurodegenerative diseases in in vitro Parkinson's disease models.
EXPERIMENTAL APPROACH
Mesencephalic neuron glia cultures and reconstituted cultures were used to investigate neurotrophic and neuroprotective effects of SAHA. We measured toxicity in dopaminergic neurons, using dopamine uptake assay and morphological analysis and expression of neurotrophic substances by enzyme-linked immunosorbent assay and real-time RT PCR.
KEY RESULTS
In mesencephalic neuron glia cultures, SAHA displayed dose- and time-dependent prolongation of the survival and protection against neurotoxin-induced neuronal death of dopaminergic neurons. Mechanistic studies revealed that the neuroprotective effects of SAHA were mediated in part by promoting release of neurotrophic factors from astroglia through inhibition of histone deacetylation.
CONCLUSION AND IMPLICATIONS
The novel neurotrophic and neuroprotective effects of SAHA demonstrated in this study suggest that further study of this HDAC inhibitor could provide a new therapeutic approach to the treatment of neurodegenerative diseases.
C1 [Hong, J. S.] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Chen, S. H.; Wu, H. M.; Chu, C. H.; Chen, S. L.; Lu, R. B.] Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70428, Taiwan.
[Chen, S. H.; Wu, H. M.; Chu, C. H.; Chen, S. L.; Lu, R. B.] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan.
[Li, X.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Wu, H. M.] Changhua Christian Hosp, Dept Neurol, Changhua, Taiwan.
[Wu, H. M.] China Med Univ, Grad Inst Acupuncture Sci, Taichung, Taiwan.
[Lu, R. B.] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70428, Taiwan.
RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM hong3@niehs.nih.gov; rblu@mail.ncku.edu.tw
FU National Cheng Kung University; Promoting Academic Excellence &
Developing World Class Research Centers, Taiwan; NIH/NIEHS
FX We thank Dr Ronald Cannon and Esteban Oyarzabal for critical reading of
the manuscript, This project was supported by a grant from the National
Cheng Kung University, Project of Promoting Academic Excellence &
Developing World Class Research Centers, Taiwan. This research was also
supported in part by the Intramural Research Program of the NIH/NIEHS.
NR 47
TC 26
Z9 26
U1 3
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD JAN
PY 2012
VL 165
IS 2
BP 494
EP 505
DI 10.1111/j.1476-5381.2011.01575.x
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 867UV
UT WOS:000298481200016
PM 21726209
ER
PT J
AU Leach, CR
Klabunde, CN
Alfano, CM
Smith, JL
Rowland, JH
AF Leach, Corinne R.
Klabunde, Carrie N.
Alfano, Catherine M.
Smith, Judith Lee
Rowland, Julia H.
TI Physician over-recommendation of mammography for terminally ill women
SO CANCER
LA English
DT Article
DE breast cancer; mammography; primary care; practice guidelines; screening
ID PRIMARY-CARE-PHYSICIANS; CANCER SCREENING RECOMMENDATIONS;
UNITED-STATES; OLDER WOMEN; SOCIETY GUIDELINES; LUNG-CANCER; BREAST;
PATIENT; SURVIVAL; ISSUES
AB BACKGROUND: There has been recent, sometimes intense, debate about when to begin screening and how often to screen women for breast cancer with mammography. However, there should be no controversy regarding screening women who are unlikely to benefit from the procedure, such as those with a serious, life-limiting illness who would not live long enough to benefit from the potential detection and treatment of breast cancer. Identifying characteristics of physicians who recommend mammography for terminally ill women can help guide efforts to minimize patient risks and make better use of health care resources. METHODS: The authors used data from a nationally representative survey of primary care physicians (PCPs) (N = 1196; response rate, 67.5%) conducted in 2006 and 2007 to examine PCPs' breast cancer screening recommendations for hypothetical patients ages 50 years, 65 years, and 80 years who were healthy, had a moderate comorbidity, or had a terminal comorbidity. RESULTS: Many PCPs (47.7%) reported that they would recommend mammography to a woman aged 50 years, 65 years, or 80 years with terminal lung cancer, indicating over-recommendation. Physician characteristics associated with over-recommending mammography included obstetrician/gynecologist (odds ratio [OR], 1.69) or internal medicine (OR, 0.45) specialty, being a woman (OR, 1.40), being a racial/ethnic minority (OR, 1.72), and working in a smaller practice (OR, 1.41). CONCLUSIONS: The current results indicated that physician over-recommendation of screening mammography among terminally ill women is common. Certain physician and practice characteristics, including specialty, were associated with over-recommending mammography. The authors concluded that an informed and shared mammography decisionmaking process for terminally ill women may eliminate unnecessary patient risks and health care expenditures. Cancer 2012; 118: 27-37. (C) 2011 American Cancer Society.
C1 [Leach, Corinne R.] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30303 USA.
[Leach, Corinne R.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Klabunde, Carrie N.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Smith, Judith Lee] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Leach, CR (reprint author), Amer Canc Soc, Behav Res Ctr, 250 Williams St, Atlanta, GA 30303 USA.
EM corinne.leach@cancer.org
FU National Cancer Institute [N02-PC-51,308]; Centers for Disease Control
and Prevention [Y3-PC-6017-01]; Agency for Healthcare Research and
Quality [Y3-PC-5019-01, Y3-PC-5019-02]
FX Funding support for this study was provided by the National Cancer
Institute (contract N02-PC-51,308), the Centers for Disease Control and
Prevention (interagency agreement Y3-PC-6017-01), and the Agency for
Healthcare Research and Quality (interagency agreements Y3-PC-5019-01
and Y3-PC-5019-02).
NR 41
TC 10
Z9 10
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 1
PY 2012
VL 118
IS 1
BP 27
EP 37
DI 10.1002/cncr.26233
PG 11
WC Oncology
SC Oncology
GA 868TW
UT WOS:000298549700006
PM 21681736
ER
PT J
AU Moore, LE
Pfeiffer, RM
Zhang, Z
Lu, KH
Fung, ET
Bast, RC
AF Moore, Lee E.
Pfeiffer, Ruth M.
Zhang, Zhen
Lu, Karen H.
Fung, Eric T.
Bast, Robert C., Jr.
TI Proteomic biomarkers in combination with CA 125 for detection of
epithelial ovarian cancer using prediagnostic serum samples from the
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
SO CANCER
LA English
DT Article
DE ovarian cancer; biomarkers; Prostate; Lung; Colorectal; Ovarian Cancer
Screening Trial; CA 125; early detection
AB BACKGROUND: When epithelial ovarian cancer is detected at an early stage (I-II), the 5-year survival rate is between 70% and 90%; whereas, when it is detected in late stages (III-IV), the 5-year survival rate slips to <30%. In a previous report, the authors observed that proteomic biomarkers and cancer antigen 125 (CA 125) exhibited a sensitivity of 84% at a specificity of 98% for identifying sera from patients who had stage I disease at the time of surgery, significantly improving the sensitivity of CA 125 alone. The challenge, however, is to detect ovarian cancer before clinical diagnosis. The current study was part of a large effort to compare different multimarker biomarker panels for the early detection of ovarian cancer. Several biomarkers were evaluated alone and in combination with CA 125 in prediagnostically collected sera from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. METHODS: Proximal prediagnostic sera from 118 women with ovarian cancer (cases) and from 951 age-matched women (controls) (8 controls per case, including 4 randomly selected from the general population, 2 with CA 125 levels >= 35 U/mL, and 2 with a positive family history of breast/ovarian cancer) were analyzed using the CA 125 immunoassay and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry to measure 7 proteins (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, b-2 microglobulin, connective tissue activating protein III), and interalpha-trypsin inhibitor heavy-chain 4). Data were analyzed by 2 statistical strategies that combined the 7 markers and CA 125 into 1 predictive score for disease classification. RESULTS: CA 125 levels were elevated (>= 35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected < 12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone. CONCLUSIONS: In contrast to earlier findings from analyzes of postdiagnostically collected sera, the addition of 7 biomarkers to CA 125 did not improve sensitivity for preclinical diagnosis beyond CA 125 alone. Cancer 2012; 118: 91-100. (C) 2011 American Cancer Society.
C1 [Moore, Lee E.; Pfeiffer, Ruth M.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Zhang, Zhen] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Fung, Eric T.] Vermillion Inc, Fremont, CA USA.
[Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
RP Moore, LE (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
EM moorele@mail.nih.gov
RI Bast, Robert/E-6585-2011
OI Bast, Robert/0000-0003-4621-8462
FU University of Texas MD Anderson SPORE in Ovarian Cancer from the
National Cancer Institute [P50 CA83639]; Golfers Against Cancer; Tracey
Jo Wilson Foundation; Mossy Foundation; National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by funds from The University of Texas MD
Anderson SPORE in Ovarian Cancer from the National Cancer Institute
(grant P50 CA83639); by philanthropic support from Golfers Against
Cancer, the Tracey Jo Wilson Foundation, and the Mossy Foundation; and
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
NR 20
TC 36
Z9 38
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JAN 1
PY 2012
VL 118
IS 1
BP 91
EP 100
DI 10.1002/cncr.26241
PG 10
WC Oncology
SC Oncology
GA 868TW
UT WOS:000298549700013
PM 21717433
ER
PT J
AU Jin, GX
Fu, CH
Zhao, H
Cui, KM
Chang, J
Wong, STC
AF Jin, Guangxu
Fu, Changhe
Zhao, Hong
Cui, Kemi
Chang, Jenny
Wong, Stephen T. C.
TI A Novel Method of Transcriptional Response Analysis to Facilitate Drug
Repositioning for Cancer Therapy
SO CANCER RESEARCH
LA English
DT Article
ID INTERACTION DATABASE; NETWORK MOTIFS; TARGETED THERAPIES; CONNECTIVITY
MAP; KNOWLEDGEBASE; SIMILARITY; SIGNATURES; DISCOVERY; GENES; TOOL
AB Little research has been done to address the huge opportunities that may exist to reposition existing approved or generic drugs for alternate uses in cancer therapy. In addition, there has been little work on strategies to reposition experimental cancer agents for testing in alternate settings that could shorten their clinical development time. Progress in each area has lagged, in part, because of the lack of systematic methods to define drug off-target effects (OTE) that might affect important cancer cell signaling pathways. In this study, we addressed this critical gap by developing an OTE-based method to repurpose drugs for cancer therapeutics, based on transcriptional responses made in cells before and after drug treatment. Specifically, we defined a new network component called cancer-signaling bridges (CSB) and integrated it with a Bayesian factor regression model (BFRM) to form a new hybrid method termed CSB-BFRM. Proof-of-concept studies were conducted in breast and prostate cancer cells and in promyelocytic leukemia cells. In each system, CSB-BFRM analysis could accurately predict clinical responses to more than 90% of drugs approved by the U. S. Food and Drug Administration and more than 75% of experimental clinical drugs that were tested. Mechanistic investigation of OTEs for several high-ranking drug-dose pairs suggested repositioning opportunities for cancer therapy, based on the ability to enforce retinoblastoma-dependent repression of important E2F-dependent cell-cycle genes. Together, our findings establish new methods to identify opportunities for drug repositioning or to elucidate the mechanisms of action of repositioned drugs. Cancer Res; 72( 1); 33-44. (C) 2011 AACR.
C1 [Jin, Guangxu; Fu, Changhe; Zhao, Hong; Cui, Kemi; Chang, Jenny; Wong, Stephen T. C.] Cornell Univ, Dept Syst Med & Bioengn, Methodist Hosp, Res Inst,Weill Med Coll, Houston, TX 77030 USA.
[Jin, Guangxu; Zhao, Hong; Cui, Kemi; Chang, Jenny; Wong, Stephen T. C.] Cornell Univ, NCI Ctr Modeling Canc Dev, Methodist Hosp, Res Inst,Weill Med Coll, Houston, TX 77030 USA.
[Chang, Jenny; Wong, Stephen T. C.] Methodist Hosp, Methodist Canc Ctr, Houston, TX 77030 USA.
RP Wong, STC (reprint author), Cornell Univ, Dept Syst Med & Bioengn, Methodist Hosp, Res Inst,Weill Med Coll, 6670 Bertner St,MC R6-414, Houston, TX 77030 USA.
EM stwong@tmhs.org
RI Jin, Guangxu/B-4627-2012
OI Jin, Guangxu/0000-0002-6616-6981
FU NIH [U54CA149196]
FX This work was supported by NIH grant U54CA149196 and John S. Dunn
Research Foundation to S. T. C. Wong.
NR 32
TC 29
Z9 29
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2012
VL 72
IS 1
BP 33
EP 44
DI 10.1158/0008-5472.CAN-11-2333
PG 12
WC Oncology
SC Oncology
GA 871RO
UT WOS:000298755600005
PM 22108825
ER
PT J
AU Fitzgerald, DP
Subramanian, P
Deshpande, M
Graves, C
Gordon, I
Qian, YZ
Snitkovsky, Y
Liewehr, DJ
Steinberg, SM
Paltan-Ortiz, JD
Herman, MM
Camphausen, K
Palmieri, D
Becerra, SP
Steeg, PS
AF Fitzgerald, Daniel P.
Subramanian, Preeti
Deshpande, Monika
Graves, Christian
Gordon, Ira
Qian, Yongzhen
Snitkovsky, Yeva
Liewehr, David J.
Steinberg, Seth M.
Paltan-Ortiz, Jose D.
Herman, Mary M.
Camphausen, Kevin
Palmieri, Diane
Becerra, S. Patricia
Steeg, Patricia S.
TI Opposing Effects of Pigment Epithelium-Derived Factor on Breast Cancer
Cell versus Neuronal Survival: Implication for Brain Metastasis and
Metastasis-Induced Brain Damage
SO CANCER RESEARCH
LA English
DT Article
ID FLUORO-JADE-B; TUMOR-GROWTH; IDENTIFICATION; ANGIOGENESIS; PEDF;
INHIBITOR; PHOTORECEPTORS; COLONIZATION; DEGENERATION; EXPRESSION
AB Brain metastases are a significant cause of morbidity and mortality for patients with cancer, yet preventative and therapeutic options remain an unmet need. The cytokine pigment epithelium-derived factor ( PEDF) is downregulated in resected human brain metastases of breast cancer compared with primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here, we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression, as supported by in vitro analyses as well as direct intracranial implantation. Notably, the suppressive effects of PEDF were not only rapid but independent of the effects of this factor on angiogenesis. Paralleling its cytotoxic effects on breast cancer cells, PEDF also exerted a prosurvival effect on neurons that shielded the brain from tumor-induced damage, as indicated by a relative 3.5-fold reduction in the number of dying neurons adjacent to tumors expressing PEDF. Our findings establish PEDF as both a metastatic suppressor and a neuroprotectant in the brain, highlighting its role as a double agent in limiting brain metastasis and its local consequences. Cancer Res; 72( 1); 144-53. (C) 2012 AACR.
C1 [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Subramanian, Preeti; Deshpande, Monika; Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
[Graves, Christian; Gordon, Ira; Camphausen, Kevin] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Snitkovsky, Yeva; Paltan-Ortiz, Jose D.; Herman, Mary M.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Qian, Yongzhen] NCI, Lab Anim Sci Program, Applicat Int Corp, Frederick, MD 21701 USA.
RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bldg 37,Room 1122, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Palmieri, Diane/B-4258-2015
FU National Cancer Institute; National Eye Institute; U.S. Department of
Defense Breast Cancer Research [W81 XWH-062-0033]; GlaxoSmithKline;
Millenium Pharmaceuticals
FX This work was supported by the intramural research programs of the
National Cancer Institute and the National Eye Institute and by the U.S.
Department of Defense Breast Cancer Research Program, grant number: W81
XWH-062-0033. Dr. Patricia Steeg's laboratory lab receives research
support from GlaxoSmithKline and Millenium Pharmaceuticals.
NR 49
TC 25
Z9 26
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2012
VL 72
IS 1
BP 144
EP 153
DI 10.1158/0008-5472.CAN-11-1904
PG 10
WC Oncology
SC Oncology
GA 871RO
UT WOS:000298755600015
PM 22215693
ER
PT J
AU Wang, CX
Liu, ZH
Woo, CW
Li, ZJ
Wang, LF
Wei, JS
Marquez, VE
Bates, SE
Jin, QH
Khan, J
Ge, K
Thiele, CJ
AF Wang, Chunxi
Liu, Zhihui
Woo, Chan-Wook
Li, Zhijie
Wang, Lifeng
Wei, Jun S.
Marquez, Victor E.
Bates, Susan E.
Jin, Qihuang
Khan, Javed
Ge, Kai
Thiele, Carol J.
TI EZH2 Mediates Epigenetic Silencing of Neuroblastoma Suppressor Genes
CASZ1, CLU, RUNX3, and NGFR
SO CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; GROUP PROTEIN EZH2; TUMOR-SUPPRESSOR;
METHYLTRANSFERASE EZH2; PROSTATE-CANCER; STEM-CELLS; CHROMOSOME 1P;
EXPRESSION; DIFFERENTIATION; REPRESSION
AB Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with an undifferentiated status and generally poor prognosis, but the basis for these characteristics remains unknown. In this study, we show that upregulation of the Polycomb protein histone methyltransferase EZH2, which limits differentiation in many tissues, is critical to maintain the undifferentiated state and poor prognostic status of NB by epigenetic repression of multiple tumor suppressor genes. We identified this role for EZH2 by examining the regulation of CASZ1, a recently identified NB tumor suppressor gene whose ectopic restoration inhibits NB cell growth and induces differentiation. Reducing EZH2 expression by RNA interference-mediated knockdown or pharmacologic inhibiton with 3-deazaneplanocin A increased CASZ1 expression, inhibited NB cell growth, and induced neurite extension. Similarly, EZH2(-/-) mouse embryonic fibroblasts (MEF) displayed 3-fold higher levels of CASZ1 mRNA compared with EZH2(+/+) MEFs. In cells with increased expression of CASZ1, treatment with histone deacetylase (HDAC) inhibitor decreased expression of EZH2 and the Polycomb Repressor complex component SUZ12. Under steady-state conditions, H3K27me3 and PRC2 components bound to the CASZ1 gene were enriched, but this enrichment was decreased after HDAC inhibitor treatment. We determined that the tumor suppressors CLU, NGFR, and RUNX3 were also directly repressed by EZH2 like CASZ1 in NB cells. Together, our findings establish that aberrant upregulation of EZH2 in NB cells silences several tumor suppressors, which contribute to the genesis and maintenance of the undifferentiated phenotype of NB tumors. Cancer Res; 72(1); 315-24. (C) 2011 AACR.
C1 [Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,CRC, Bethesda, MD 20892 USA.
[Wang, Lifeng; Wei, Jun S.; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bates, Susan E.] NCI, Mol Therapeut Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jin, Qihuang; Ge, Kai] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD USA.
[Marquez, Victor E.] NCI, Chem Biol Lab, NIH, Frederick, MD 21701 USA.
RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,CRC, 1-3940,10 Ctr Dr,MSC 1105, Bethesda, MD 20892 USA.
EM thielec@mail.nih.gov
RI Wang, Lifeng/I-4888-2012; Khan, Javed/P-9157-2014;
OI Wang, Lifeng/0000-0003-4752-6547; Khan, Javed/0000-0002-5858-0488; Ge,
Kai/0000-0002-7442-5138
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported and funded by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 50
TC 58
Z9 60
U1 0
U2 9
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 JAN 1
PY 2012
VL 72
IS 1
BP 315
EP 324
DI 10.1158/0008-5472.CAN-11-0961
PG 10
WC Oncology
SC Oncology
GA 871RO
UT WOS:000298755600031
PM 22068036
ER
PT J
AU Sarkar, K
Rey, S
Zhang, XJ
Sebastian, R
Marti, GP
Fox-Talbot, K
Cardona, AV
Du, JK
Tan, YS
Liu, LX
Lay, F
Gonzalez, FJ
Harmon, JW
Semenza, GL
AF Sarkar, Kakali
Rey, Sergio
Zhang, Xianjie
Sebastian, Raul
Marti, Guy P.
Fox-Talbot, Karen
Cardona, Amanda V.
Du, Junkai
Tan, Yee Sun
Liu, Lixin
Lay, Frank
Gonzalez, Frank J.
Harmon, John W.
Semenza, Gregg L.
TI Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and
homing of bone marrow-derived angiogenic cells
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Hypoxia; Wound healing; Conditional knockout; Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1; PROGENITOR CELLS;
LIMB ISCHEMIA; DIABETIC MICE; TRANSCRIPTIONAL REGULATION; TUMOR
ANGIOGENESIS; GENE-THERAPY; IN-VIVO; EXPRESSION
AB Aims Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of HIF-1 alpha and HIF-1 beta subunits. HIF-1 is known to promote tissue vascularization by activating the transcription of genes encoding angiogenic factors, which bind to receptors on endothelial cells (ECs) and bone marrow-derived angiogenic cells (BMDACs). In this study, we analysed whether HIF-1 activity in the responding ECs and BMDACs is also required for cutaneous vascularization during burn wound healing.
Methods and results We generated mice with floxed alleles at the Hif1a or Arnt locus encoding HIF-1 alpha and HIF-1 beta, respectively. Expression of Cre recombinase was driven by the Tie2 gene promoter, which is expressed in ECs and bone marrow cells. Tie2Cre(+) and Tie2Cre(-) mice were subjected to burn wounds of reproducible diameter and depth. Deficiency of HIF-1 alpha or HIF-1 beta in Tie2-lineage cells resulted in delayed wound closure, reduced vascularization, decreased cutaneous blood flow, impaired BMDAC mobilization, and decreased BMDAC homing to burn wounds.
Conclusion HIF-1 activity in Tie2-lineage cells is required for the mobilization and homing of BMDACs to cutaneous burn wounds and for the vascularization of burn wound tissue.
C1 [Zhang, Xianjie; Sebastian, Raul; Marti, Guy P.; Du, Junkai; Liu, Lixin; Lay, Frank; Harmon, John W.] Johns Hopkins Univ, Sch Med, Hendrix Burn Lab, Baltimore, MD 21205 USA.
[Rey, Sergio; Cardona, Amanda V.; Tan, Yee Sun; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Sarkar, Kakali; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Sarkar, Kakali; Rey, Sergio; Cardona, Amanda V.; Tan, Yee Sun; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA.
[Zhang, Xianjie] Capital Med Univ, Beijing Tiantan Hosp, Sect Surg Sci, Beijing, Peoples R China.
[Fox-Talbot, Karen] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Zhang, Xianjie; Sebastian, Raul; Marti, Guy P.; Du, Junkai; Liu, Lixin; Lay, Frank; Harmon, John W.] Johns Hopkins Univ, Sch Med, Sect Surg Sci, Baltimore, MD 21205 USA.
RP Harmon, JW (reprint author), Johns Hopkins Univ, Sch Med, Sect Surg Sci, Baltimore, MD 21205 USA.
EM jharmon2@jhmi.edu; gsemenza@jhmi.edu
RI Rey, Sergio/B-6370-2009;
OI marti, guy/0000-0003-1147-4001; Rey, Sergio/0000-0001-8954-7712
FU National Institute of General Medical Sciences [P20-GM078494]; Johns
Hopkins Institute for Cell Engineering; Johns Hopkins University
FX This work was supported by grant P20-GM078494 from the National
Institute of General Medical Sciences, the Johns Hopkins Institute for
Cell Engineering, and the Hendrix Burn Fund of Johns Hopkins University.
G.L.S. is the C. Michael Armstrong Professor at the Johns Hopkins
University School of Medicine.
NR 52
TC 16
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U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JAN
PY 2012
VL 93
IS 1
BP 162
EP 169
DI 10.1093/cvr/cvr282
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 866LF
UT WOS:000298381600021
PM 22028336
ER
PT J
AU Ball, WS
Byars, AW
Schapiro, M
Bommer, W
Carr, A
German, A
Dunn, S
Rivkin, MJ
Waber, D
Mulkern, R
Vajapeyam, S
Chiverton, A
Davis, P
Koo, J
Marmor, J
Mrakotsky, C
Robertson, R
McAnulty, G
Brandt, ME
Fletcher, JM
Kramer, LA
Yang, G
McCormack, C
Hebert, KM
Volero, H
Botteron, K
McKinstry, RC
Warren, W
Nishino, T
Almli, CR
Todd, R
Constantino, J
McCracken, JT
Levitt, J
Alger, J
O'Neill, J
Toga, A
Asarnow, R
Fadale, D
Heinichen, L
Ireland, C
Wang, DJ
Moss, E
Zimmerman, RA
Bintliff, B
Bradford, R
Newman, J
Evans, AC
Arnaoutelis, R
Pike, GB
Collins, DL
Leonard, G
Paus, T
Zijdenbos, A
Das, S
Fonov, V
Fu, L
Harlap, J
Leppert, I
Milovan, D
Vins, D
Zeffiro, T
Van Meter, J
Lange, N
Froimowitz, MP
Botteron, K
Almli, CR
Rainey, C
Henderson, S
Nishino, T
Warren, W
Edwards, JL
Dubois, D
Smith, K
Singer, T
Wilber, AA
Pierpaoli, C
Basser, PJ
Chang, LC
Walker, L
Rumsey, J
Baskir, L
Stanford, L
Sirocco, K
Gwinn-Hardy, K
Spinella, G
McCracken, JT
Alger, JR
Levitt, J
AF Ball, William S.
Byars, Anna Weber
Schapiro, Mark
Bommer, Wendy
Carr, April
German, April
Dunn, Scott
Rivkin, Michael J.
Waber, Deborah
Mulkern, Robert
Vajapeyam, Sridhar
Chiverton, Abigail
Davis, Peter
Koo, Julie
Marmor, Jacki
Mrakotsky, Christine
Robertson, Richard
McAnulty, Gloria
Brandt, Michael E.
Fletcher, Jack M.
Kramer, Larry A.
Yang, Grace
McCormack, Cara
Hebert, Kathleen M.
Volero, Hilda
Botteron, Kelly
McKinstry, Robert C.
Warren, William
Nishino, Tomoyuki
Almli, C. Robert
Todd, Richard
Constantino, John
McCracken, James T.
Levitt, Jennifer
Alger, Jeffrey
O'Neill, Joseph
Toga, Arthur
Asarnow, Robert
Fadale, David
Heinichen, Laura
Ireland, Cedric
Wang, Dah-Jyuu
Moss, Edward
Zimmerman, Robert A.
Bintliff, Brooke
Bradford, Ruth
Newman, Janice
Evans, Alan C.
Arnaoutelis, Rozalia
Pike, G. Bruce
Collins, D. Louis
Leonard, Gabriel
Paus, Tomas
Zijdenbos, Alex
Das, Samir
Fonov, Vladimir
Fu, Luke
Harlap, Jonathan
Leppert, Ilana
Milovan, Denise
Vins, Dario
Zeffiro, Thomas
Van Meter, John
Lange, Nicholas
Froimowitz, Michael P.
Botteron, Kelly
Almli, C. Robert
Rainey, Cheryl
Henderson, Stan
Nishino, Tomoyuki
Warren, William
Edwards, Jennifer L.
Dubois, Diane
Smith, Karla
Singer, Tish
Wilber, Aaron A.
Pierpaoli, Carlo
Basser, Peter J.
Chang, Lin-Ching
Walker, Lindsay
Rumsey, Judith
Baskir, Lauren
Stanford, Laurence
Sirocco, Karen
Gwinn-Hardy, Katrina
Spinella, Giovanna
McCracken, James T.
Alger, Jeffry R.
Levitt, Jennifer
CA Brain Dev Cooperative Grp
TI Total and Regional Brain Volumes in a Population-Based Normative Sample
from 4 to 18 Years: The NIH MRI Study of Normal Brain Development
SO CEREBRAL CORTEX
LA English
DT Article
DE adolescents; brain volumes; children; healthy; MRI
ID BODY-MASS INDEX; CEREBRAL ASYMMETRY; UNITED-STATES; MATTER VOLUME;
PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; TEMPORALE ASYMMETRY;
HEALTHY-INDIVIDUALS; SEXUAL-DIMORPHISM; HUMAN OBESITY
AB Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.
C1 [Lange, Nicholas] McLean Hosp, Neurostat Lab, Belmont, MA 02478 USA.
[Ball, William S.; Byars, Anna Weber; Schapiro, Mark; Bommer, Wendy; Carr, April; German, April; Dunn, Scott; Brain Dev Cooperative Grp] Childrens Hosp Med Ctr Cincinnati, Cincinnati, OH USA.
[Rivkin, Michael J.; Waber, Deborah; Mulkern, Robert; Vajapeyam, Sridhar; Chiverton, Abigail; Davis, Peter; Koo, Julie; Marmor, Jacki; Mrakotsky, Christine; Robertson, Richard; McAnulty, Gloria] Childrens Hosp Boston, Boston, MA USA.
[Brandt, Michael E.; Fletcher, Jack M.; Kramer, Larry A.; Yang, Grace; McCormack, Cara; Hebert, Kathleen M.; Volero, Hilda] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77225 USA.
[Botteron, Kelly; Almli, C. Robert; Rainey, Cheryl; Henderson, Stan; Nishino, Tomoyuki; Warren, William; Edwards, Jennifer L.; Dubois, Diane; Smith, Karla; Singer, Tish; Wilber, Aaron A.] Washington Univ, Clin Coordinating Ctr, St Louis, MO 63130 USA.
[O'Neill, Joseph; McCracken, James T.; Alger, Jeffry R.; Levitt, Jennifer] Univ Calif Los Angeles, Spect Proc Ctr, Los Angeles, CA 90024 USA.
[Wang, Dah-Jyuu; Moss, Edward; Zimmerman, Robert A.; Bintliff, Brooke; Bradford, Ruth; Newman, Janice] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Evans, Alan C.; Arnaoutelis, Rozalia; Pike, G. Bruce; Collins, D. Louis; Leonard, Gabriel; Paus, Tomas; Zijdenbos, Alex; Das, Samir; Fonov, Vladimir; Fu, Luke; Harlap, Jonathan; Leppert, Ilana; Milovan, Denise; Vins, Dario] McGill Univ, Data Coordinating Ctr, Montreal, PQ H3A 2T5, Canada.
[Zeffiro, Thomas; Van Meter, John] Georgetown Univ, Washington, DC 20057 USA.
[Lange, Nicholas] Harvard Univ, McLean Hosp, Cambridge, MA 02138 USA.
[Pierpaoli, Carlo; Basser, Peter J.; Chang, Lin-Ching; Walker, Lindsay] NIH, Diffus Tensor Proc Ctr, Bethesda, MD 20892 USA.
RP Ball, WS (reprint author), McLean Hosp, Neurostat Lab, 115 Mill St, Belmont, MA 02478 USA.
EM nlange@hms.harvard.edu
RI Basser, Peter/H-5477-2011; Pike, Bruce/K-5562-2014;
OI Pike, Bruce/0000-0001-8924-683X; Freund, Lisa/0000-0003-2095-4023;
Gwinn, Katrina/0000-0002-8277-651X
FU National Institute of Child Health and Human Development; National
Institute on Drug Abuse; National Institute of Mental Health; National
Institute of Neurological Disorders and Stroke [N01-HD02-3343,
N01-MH9-0002, N01-NS-9-2314, -2315, -2316, -2317, -2319, -2320, NS34783]
FX This project was supported with Federal funds from the National
Institute of Child Health and Human Development, the National Institute
on Drug Abuse, the National Institute of Mental Health, and the National
Institute of Neurological Disorders and Stroke (Contract #s
N01-HD02-3343; N01-MH9-0002; N01-NS-9-2314, -2315, -2316, -2317, -2319,
and -2320; and NS34783).
NR 63
TC 101
Z9 102
U1 3
U2 26
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD JAN
PY 2012
VL 22
IS 1
BP 1
EP 12
DI 10.1093/cercor/bhr018
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 863TI
UT WOS:000298190500001
ER
PT J
AU Palmore, TN
Henderson, DK
AF Palmore, Tara N.
Henderson, David K.
TI Big Brother is Washing. Video Surveillance for Hand Hygiene Adherence,
Through the Lenses of Efficacy and Privacy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID NOSOCOMIAL INFECTIONS; CARE; PROGRAM; DEVICE
C1 [Palmore, Tara N.; Henderson, David K.] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA.
[Palmore, Tara N.; Henderson, David K.] NIH, Hosp Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Henderson, DK (reprint author), NIH, Off Deputy Director Clin Care, Ctr Clin, Bldg 10,Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 12
TC 4
Z9 5
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JAN 1
PY 2012
VL 54
IS 1
BP 8
EP 9
DI 10.1093/cid/cir781
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 866LX
UT WOS:000298383500004
PM 22109949
ER
PT J
AU Bennett, J
AF Bennett, John
TI Companion Drugs for Amphotericin B in Cryptococcal Meningitis:
Flucytosine, Fluconazole, or ... Nothing?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Bennett, J (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 10 Ctr Dr,Bldg 10,Rm 11C304, Bethesda, MD 20892 USA.
EM jbennett@niaid.nih.gov
FU Intramural NIH HHS
NR 7
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JAN 1
PY 2012
VL 54
IS 1
BP 129
EP 130
DI 10.1093/cid/cir758
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 866LX
UT WOS:000298383500025
PM 22052886
ER
PT J
AU Martin, S
Calabrese, SK
Wolters, PL
Walker, KA
Warren, K
Hazra, R
AF Martin, Staci
Calabrese, Sarah K.
Wolters, Pamela L.
Walker, Katherine A.
Warren, Katherine
Hazra, Rohan
TI Family Functioning and Coping Styles in Families of Children With Cancer
and HIV Disease
SO CLINICAL PEDIATRICS
LA English
DT Article
DE family functioning; coping; social support; cancer; HIV disease
ID PSYCHOLOGICAL ADJUSTMENT; ASSESSMENT DEVICE; CHILDHOOD-CANCER; SOCIAL
SUPPORT; HIV/AIDS; STIGMA; STRESS; ADOLESCENTS; STRATEGIES; ILLNESS
AB Disease-specific characteristics of pediatric illnesses may influence the functioning of families and the coping responses they enact. This study compared family functioning and coping styles within and between 2 different medical groups: families of children with cancer (n = 44) and HIV disease (n = 65). Most caregivers reported healthy family functioning, and no between-group differences in functioning emerged. However, with regard to coping, more reliance on social support was indicated among the cancer group. Also, the HIV group largely sought support from family, whereas both family and nonfamily support were sought among the cancer group. Better functioning was related to reframing, an active coping style, within the cancer group and passive coping within the HIV group. Thus, coping strategies and their implications for family functioning vary by condition. Researchers should avoid combining various illness groups indiscriminately. Likewise, clinicians should be sensitive to disease-specific factors when helping families learn to cope with illness-related stressors.
C1 [Martin, Staci] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Calabrese, Sarah K.] George Washington Univ, Washington, DC USA.
[Walker, Katherine A.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Martin, S (reprint author), NCI, Pediat Oncol Branch, 9030 Old Georgetown Rd, Bethesda, MD 20892 USA.
EM martins@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Medical Illness Counseling Center [HHSN261200477004C];
SAIC-Frederick, Inc. [HHSN261200800001E]; National Institute of Mental
Health [F31-MH085584]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, as well as Federal Contracts HHSN261200477004C with the
Medical Illness Counseling Center and HHSN261200800001E with
SAIC-Frederick, Inc. Sarah K. Calabrese was supported by Grant Number
F31-MH085584 from the National Institute of Mental Health.
NR 32
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U1 2
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD JAN
PY 2012
VL 51
IS 1
BP 58
EP 64
DI 10.1177/0009922811417300
PG 7
WC Pediatrics
SC Pediatrics
GA 870GC
UT WOS:000298656200008
PM 21868594
ER
PT J
AU Carson, SS
Vu, M
Danis, M
Camhi, SL
Scheunemann, LP
Cox, CE
Hanson, LC
Nelson, JE
AF Carson, Shannon S.
Vu, Maihan
Danis, Marion
Camhi, Sharon L.
Scheunemann, Leslie P.
Cox, Christopher E.
Hanson, Laura C.
Nelson, Judith E.
TI Development and validation of a printed information brochure for
families of chronically critically ill patients
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE communication; critically ill; information sharing; mechanical
ventilation; tracheostomies; validation studies
ID INTENSIVE-CARE-UNIT; PROLONGED MECHANICAL VENTILATION; CHRONIC CRITICAL
ILLNESS; DECISION-MAKING; HEALTH; COMMUNICATION; DEPRESSION; RELATIVES;
ANXIETY; MEMBERS
AB Objective: Families and other surrogate decisionmakers for chronically critically ill patients often lack information about patient prognosis or options for care. This study describes an approach to develop and validate a printed information brochure about chronic critical illness aimed at improving comprehension of the disease process and outcomes for patients' families and other surrogate decisionmakers.
Design: Investigators reviewed existing literature to identify key domains of informational needs. Content of these domains was incorporated in a draft brochure that included graphics and a glossary of terms. Clinical sensibility, balance, and emotional sensitivity of the draft brochure were tested in a series of evaluations by cohorts of experienced clinicians (n = 49) and clinical content experts (n = 8) with revisions after each review.
Subjects: Cognitive testing of the brochure was performed through interviews of ten representative family members of chronically critically ill patients with quantitative and qualitative analysis of responses.
Measurements and Main Results: Clinical sensibility and balance were rated in the two most favorable categories on a five-point scale by more than two thirds of clinicians and content experts. After review, family members described the brochure as clear and readable and recommended that the brochure be delivered to family members by clinicians followed by a discussion of its contents. They indicated that the glossary was useful and recommended supplementation by additional lists of local resources. After reading the brochure, their prognostic estimates became more consistent with actual outcomes.
Conclusions: We have developed and validated a printed information brochure that may improve family comprehension of chronic critical illness and its outcomes. The structured process that is described can serve as a template for the development of other information aids for use with seriously ill populations. (Crit Care Med 2012; 40:73-78)
C1 [Carson, Shannon S.; Scheunemann, Leslie P.; Hanson, Laura C.] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA.
[Vu, Maihan] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA.
[Danis, Marion] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Camhi, Sharon L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Camhi, Sharon L.] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA.
[Cox, Christopher E.] Duke Univ, Dept Med, Durham, NC USA.
[Nelson, Judith E.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Carson, SS (reprint author), Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA.
EM scarson@med.unc.edu
FU Department of Bioethics, National Institutes of Health Clinical Center
FX This work was funded by the Department of Bioethics, National Institutes
of Health Clinical Center. The views expressed here are those of the
authors and do not necessarily reflect the policies of the US Department
of Health and Human Services or the National Institutes of Health.
NR 23
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U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 73
EP 78
DI 10.1097/CCM.0b013e31822d7901
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800011
PM 21926610
ER
PT J
AU Berra, L
Coppadoro, A
Bittner, EA
Kolobow, T
Laquerriere, P
Pohlmann, JR
Bramati, S
Moss, J
Pesenti, A
AF Berra, Lorenzo
Coppadoro, Andrea
Bittner, Edward A.
Kolobow, Theodor
Laquerriere, Patrice
Pohlmann, Joshua R.
Bramati, Simone
Moss, Joel
Pesenti, Antonio
TI A clinical assessment of the Mucus Shaver: A device to keep the
endotracheal tube free from secretions
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE bacterial biofilm; endotracheal tube; endotracheal tube occlusion;
endotracheal tube suctioning; mechanical ventilation; Mucus Shaver;
secretion removal; ventilator-associated pneumonia
ID VENTILATOR-ASSOCIATED PNEUMONIA; PSEUDOMONAS-AERUGINOSA BIOFILMS;
MECHANICAL VENTILATION; BACTERIAL-COLONIZATION; TRACHEAL TUBE;
INTUBATION; PREVENTION; RESISTANCE; INFECTION; DIAMETER
AB Objective: We evaluated a new device designed to clean the endotracheal tube in mechanically ventilated patients, the Mucus Shaver.
Design: Prospective, randomized trial.
Setting: University hospital intensive care unit.
Patients: We enrolled 24 patients expected to remain ventilated for >72 hrs.
Interventions: The Mucus Shaver is a concentric inflatable catheter for the removal of mucus and secretions from the interior surface of the endotracheal tube. The Mucus Shaver is advanced to the distal endotracheal tube tip, inflated, and subsequently withdrawn over a period of 3-5 secs. Patients were prospectively randomized within 2 hrs of intubation to receive standard endotracheal tube suctioning treatment or standard suctioning plus Mucus Shaver use until extubation.
Measurements and Main Results: During the study period, demographic data, recent medical history, adverse events, and staff evaluation of the Mucus Shaver were recorded. At extubation, each endotracheal tube was removed, cultured, and analyzed by scanning electron microscopy. Twelve patients were assigned to the study group and 12 were assigned to the control group. No adverse events related to the use of the Mucus Shaver were observed. At extubation, only one endotracheal tube from the Mucus Shaver group was colonized, whereas in the control group ten endotracheal tubes were colonized (8% vs. 83%; p < .001). Scanning electron microscopy showed little secretions on the endotracheal tubes from the study group, whereas thick bacterial deposits were present on all the endotracheal tubes from the control group (p < .001 by Fisher exact test, using a maximum biofilm thickness of 30 mu m as cut-off). The nursing staff was satisfied by the overall safety, feasibility, and efficacy of the Mucus Shaver.
Conclusions: The Mucus Shaver is a safe, feasible, and efficient device for endotracheal tube cleaning in the clinical setting. The Mucus Shaver is helpful in preventing endotracheal tube colonization by potentially harmful microorganisms. (Crit Care Med 2012; 40:119-124)
C1 [Berra, Lorenzo; Coppadoro, Andrea; Bittner, Edward A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA.
[Coppadoro, Andrea; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Milan, Italy.
[Kolobow, Theodor] NHLBI, Sect Pulm & Cardiac Assist Devices, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA.
[Laquerriere, Patrice] Univ Reims, INSERM, Electron Microscopy Lab, Reims, France.
[Pohlmann, Joshua R.] Univ Michigan, Dept Gen Surg, Ann Arbor, MI 48109 USA.
[Bramati, Simone] San Gerardo Hosp, Microbiol & Virol Dept, Monza, Italy.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Pesenti, Antonio] San Gerardo Hosp, Dept Perioperat Med & Intens Care, Monza, Italy.
RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA.
EM lberra@partners.org
RI Pesenti, Antonio/H-7483-2012; Laquerriere, Patrice/P-1025-2016
OI Laquerriere, Patrice/0000-0001-7637-9094
FU National Heart, Lung, and Blood Institute, Division of International
Research, National Institutes of Health, Department of Health and Human
Services, Bethesda, Maryland; Department of Perioperative Medicine and
Intensive Care, San Gerardo Hospital, Monza, Italy; National Institutes
of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland
FX Supported, in part, by the National Heart, Lung, and Blood Institute,
Division of International Research, National Institutes of Health,
Department of Health and Human Services, Bethesda, Maryland, and by the
Department of Perioperative Medicine and Intensive Care, San Gerardo
Hospital, Monza, Italy. Dr. Moss and Dr. Kolobow were supported by the
Intramural Research Program, National Institutes of Health, National
Heart, Lung, and Blood Institute, Bethesda, Maryland.
NR 30
TC 37
Z9 38
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 119
EP 124
DI 10.1097/CCM.0b013e31822e9fe3
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800017
PM 21926595
ER
PT J
AU Hicks, CW
Sweeney, DA
Danner, RL
Eichacker, PQ
Suffredini, AF
Feng, J
Sun, JF
Behrend, EN
Solomon, SB
Natanson, C
AF Hicks, Caitlin W.
Sweeney, Daniel A.
Danner, Robert L.
Eichacker, Peter Q.
Suffredini, Anthony F.
Feng, Jing
Sun, Junfeng
Behrend, Ellen N.
Solomon, Steven B.
Natanson, Charles
TI Efficacy of selective mineralocorticoid and glucocorticoid agonists in
canine septic shock
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE animal; corticosteroids; infection; models; sepsis
ID HYPERRENINEMIC HYPOALDOSTERONISM; SEVERE SEPSIS; CRITICALLY-ILL;
UNITED-STATES; ALDOSTERONE; CORTICOSTEROIDS; HYDROCORTISONE;
METAANALYSIS; MECHANISMS; RECEPTOR
AB Objective: Corticosteroid regimens that stimulate both mineralocorticoid and glucocorticoid pathways consistently reverse vasopressor-dependent hypotension in septic shock but have variable effects on survival. The objective of this study was to determine whether exogenous mineralocorticoid and glucocorticoid treatments have distinct effects and whether the timing of administration alters their effects in septic shock.
Design, Setting, Subjects, and Interventions: Desoxycorticosterone, a selective mineralocorticoid agonist; dexamethasone, a selective glucocorticoid agonist; and placebo were administered either several days before (prophylactic) or immediately after (therapeutic) infectious challenge and continued for 96 hrs in 74 canines with staphylococcal pneumonia.
Measurements and Main Results: Effects of desoxycorticosterone and dexamethasone were different and opposite depending on timing of administration for survival (p = .05); fluid requirements (p = .05); central venous pressures (p <= .007); indicators of hemoconcentration (i.e., sodium [p = .0004], albumin [p = .05], and platelet counts [p = .02]); interleukin-6 levels (p = .04); and cardiac dysfunction (p = .05). Prophylactic desoxycorticosterone treatment significantly improved survival, shock, and all the other outcomes stated, but therapeutic desoxycorticosterone did not. Conversely, prophylactic dexamethasone was much less effective for improving these outcomes compared with therapeutic dexamethasone with the exception of shock reversal. Prophylactic dexamethasone given before sepsis induction also significantly reduced serum aldosterone and cortisol levels and increased body temperature and lactate levels compared with therapeutic dexamethasone (p <= .05), consistent with adrenal suppression.
Conclusions: In septic shock, mineralocorticoids are only beneficial if given prophylactically, whereas glucocorticoids are most beneficial when given close to the onset of infection. Prophylactic mineralocorticoids should be further investigated in patients at high risk to develop sepsis, whereas glucocorticoids should only be administered therapeutically to prevent adrenal suppression and worse outcomes. (Crit Care Med 2012; 40:199-207)
C1 [Hicks, Caitlin W.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Hicks, Caitlin W.] Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, Bethesda, MD USA.
[Hicks, Caitlin W.; Danner, Robert L.; Eichacker, Peter Q.; Suffredini, Anthony F.; Feng, Jing; Sun, Junfeng; Solomon, Steven B.; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sweeney, Daniel A.] Washington Hosp, Med Intensivist Program, Fremont, CA USA.
[Behrend, Ellen N.] Auburn Univ, Coll Vet Med, Dept Clin Sci, Auburn, AL 36849 USA.
RP Hicks, CW (reprint author), Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
EM hicksc@ccf.org
RI Hicks, Caitlin/E-8849-2012;
OI Hicks, Caitlin/0000-0001-7638-1936
FU National Institutes of Health; Howard Hughes Medical Institute
FX This study was funded, in part, by the National Institutes of Health and
the Howard Hughes Medical Institute. All work pertaining to this
manuscript was performed at the National Institutes of Health (NIH). The
study was supported by NIH intramural funds but the opinions expressed
herein do not necessarily represent the opinions of the US Government.
NR 41
TC 12
Z9 13
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 199
EP 207
DI 10.1097/CCM.0b013e31822efa14
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800029
PM 21926575
ER
PT J
AU Gormley, NJ
Bronstein, AC
Rasimas, JJ
Pao, M
Wratney, AT
Sun, JF
Austin, HA
Suffredini, AF
AF Gormley, Nicole J.
Bronstein, Alvin C.
Rasimas, Joseph J.
Pao, Maryland
Wratney, Angela T.
Sun, Junfeng
Austin, Howard A.
Suffredini, Anthony F.
TI The rising incidence of intentional ingestion of ethanol-containing hand
sanitizers
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE alcohol poisoning; ethanol hand sanitizer; hand sanitizer ingestion;
NPDS
ID HOSPITALIZED PATIENT; ALCOHOL; INTOXICATION; ISOPROPANOL; HYGIENE
AB Objective: To describe a case of intentional ingestion of hand sanitizer in our hospital and to review published cases and those reported to the American Association of Poison Control Centers' National Poison Data System.
Design: A case report, a literature review of published cases, and a query of the National Poison Data System.
Setting: Medical intensive care unit.
Patient: Seventeen-yr-old male 37-kg with an intentional ingestion of a hand sanitizer product into his gastrostomy tube.
Interventions: Intubation, ventilation, and hemodialysis.
Measurements and Main Results: Incidence and outcome of reported cases of unintentional and intentional ethanol containing-hand sanitizer ingestion in the United States from 2005 through 2009. A literature search found 14 detailed case reports of intentional alcohol-based hand sanitizer ingestions with one death. From 2005 to 2009, the National Poison Data System received reports of 68,712 exposures to 96 ethanol-based hand sanitizers. The number of new cases increased by an average of 1,894 (95% confidence interval [CI] 1266-2521) cases per year (p = .002). In 2005, the rate of exposures, per year, per million U. S. residents was 33.7 (95% CI 28.4-39.1); from 2005 to 2009, this rate increased on average by 5.87 per year (95% CI 3.70-8.04; p = .003). In 2005, the rate of intentional exposures, per year, per million U. S. residents, was 0.68 (95% CI 0.17-1.20); from 2005 to 2009, this rate increased on average by 0.32 per year (95% CI 0.11-0.53; p = .02).
Conclusions: The number of new cases per year of intentional hand sanitizer ingestion significantly increased during this 5-yr period. Although the majority of cases of hand sanitizer ingestion have a favorable outcome, 288 moderate and 12 major medical outcomes were reported in this National Poison Data System cohort. Increased awareness of the risks associated with intentional ingestion is warranted, particularly among healthcare providers caring for persons with a history of substance abuse, risk-taking behavior, or suicidal ideation. (Crit Care Med 2012; 40: 290-294)
C1 [Gormley, Nicole J.; Sun, Junfeng; Suffredini, Anthony F.] NCI, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Bronstein, Alvin C.] Univ Colorado, Sch Med, Rocky Mt Poison Ctr, Denver, CO USA.
[Rasimas, Joseph J.; Pao, Maryland] NIMH, Bethesda, MD 20892 USA.
[Wratney, Angela T.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Austin, Howard A.] NIDDK, Bethesda, MD USA.
RP Gormley, NJ (reprint author), NCI, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
EM asuffredini@cc.nih.gov
FU Clinical Center, National Institutes of Health (NIH); National Institute
of Mental Health; National Institute of Diabetes and Digestive and
Kidney Diseases, at the NIH, Bethesda, MD; American Association of
Poison Control Centers' National Poison Data System, Rocky Mountain
Poison Center, Denver, CO
FX This study was supported by the Intramural Research Programs of the
Clinical Center, National Institutes of Health (NIH), the National
Institute of Mental Health, and the National Institute of Diabetes and
Digestive and Kidney Diseases, at the NIH, Bethesda, MD, and the
American Association of Poison Control Centers' National Poison Data
System, Rocky Mountain Poison Center, Denver, CO. These organizations
provided material support for design and conduct of the study;
collection, management, analysis of the data; and preparation of the
manuscript.
NR 23
TC 8
Z9 8
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 290
EP 294
DI 10.1097/CCM.0b013e31822f09c0
PG 5
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800043
PM 21926580
ER
PT J
AU Han, SH
Sevransky, J
AF Han, Seung-Hye
Sevransky, Jonathan
TI Another "negative" acute lung injury trial
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE acute lung injury; acute respiratory distress syndrome; clinical trials;
sepsis
ID TIDAL VOLUME VENTILATION; STRATEGIES; ABSENCE
C1 [Han, Seung-Hye] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Sevransky, Jonathan] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA.
RP Han, SH (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
NR 10
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 315
EP 316
DI 10.1097/CCM.0b013e318232d307
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800056
PM 22179356
ER
PT J
AU Carlson, DE
AF Carlson, Drew E.
TI Are you having a good day: A passing nicety or a fundamental question in
the intensive care unit?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE circadian; clock genes; critical illness; diurnal; sepsis; trauma
ID CIRCADIAN-RHYTHM; GENE-EXPRESSION; CLOCK; SEPSIS; SLEEP; TIME
C1 NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Carlson, DE (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 15
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 344
EP 345
DI 10.1097/CCM.0b013e318232d2e0
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800075
PM 22179375
ER
PT J
AU Danis, M
AF Danis, Marion
TI Thorny questions on the way to disclosing rationing
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE disclosure; intensive care; public opinion; rationing; resource
allocation; triage
ID INTENSIVE-CARE; BEDSIDE; TRIAGE; MORTALITY; ADMISSION
C1 Natl Inst Hlth Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
RP Danis, M (reprint author), Natl Inst Hlth Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
NR 13
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2012
VL 40
IS 1
BP 347
EP 348
DI 10.1097/CCM.0b013e31823291ea
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 866KO
UT WOS:000298379800077
PM 22179377
ER
PT J
AU Ramanathan, HN
Ye, YH
AF Ramanathan, Harish N.
Ye, Yihong
TI Cellular strategies for making monoubiquitin signals
SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Ubiquitin; monoubiquitination; ubiquitin conjugating enzymes/E2;
histone; coupled monoubiquitination; ubiquitin-like proteins; ubiquitin
chain; endocytosis
ID UBIQUITIN-CONJUGATING ENZYME; HISTONE H2B MONOUBIQUITINATION;
ATP-DEPENDENT PROTEOLYSIS; CRYSTAL-STRUCTURE; CHAIN FORMATION;
DNA-REPAIR; SACCHAROMYCES-CEREVISIAE; MOLECULAR-MECHANISMS;
POLYUBIQUITIN CHAINS; FUNCTIONAL DIVERSITY
AB Post-translational modification of proteins with ubiquitin regulates a variety of eukaryotic cellular processes. Ubiquitin can be conjugated to substrates either as a single moiety (monoubiquitination) or as isopeptide bond-linked chains (polyubiquitination), creating an array of ubiquitin signals. It has been established that monoubiquitination can serve important functions in many biological processes such as the regulation of gene transcription, protein trafficking, and DNA repair. Surprisingly, little is known about the mechanisms by which monoubiquitin signals are produced in the cell. Here, we discuss the potential cellular strategies for generating monoubiquitinated proteins using a few, relatively well characterized examples of monoubiquitinated proteins. These strategies include coupling ubiquitination to low affinity ubiquitin binding, using monoubiquitination-dedicated E2 conjugating enzymes, and restricting ubiquitin chain elongation. Some of these principles may be applicable to protein modifications involving ubiquitin like proteins (UBLs), which often occur in monomeric form.
C1 [Ramanathan, Harish N.; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
RI RAMANATHAN, HARISH/B-1274-2013
OI RAMANATHAN, HARISH/0000-0001-6073-2981
FU NIH; National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK)
FX The authors declare no competing financial interests. The authors'
research is supported by the NIH intramural AIDS Targeted Antiviral
Program (IATAP) and by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 94
TC 22
Z9 22
U1 1
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-9238
J9 CRIT REV BIOCHEM MOL
JI Crit. Rev. Biochem. Mol. Biol.
PD JAN
PY 2012
VL 47
IS 1
BP 17
EP 28
DI 10.3109/10409238.2011.620943
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 863TA
UT WOS:000298189700002
PM 21981143
ER
PT J
AU Wang, PY
Zhuang, J
Hwang, PM
AF Wang, Ping-yuan
Zhuang, Jie
Hwang, Paul M.
TI p53: exercise capacity and metabolism
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE aerobic exercise; cancer; metabolism; mitochondria; p53
ID TUMOR-SUPPRESSOR P53; ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE;
AXIS IN-VIVO; MITOCHONDRIAL RESPIRATION; PHYSICAL-ACTIVITY; DNA-DAMAGE;
P53-INDUCIBLE REGULATOR; ANTIOXIDANT FUNCTION; ENDURANCE EXERCISE
AB Purpose of review
There is an inverse relationship between cancer incidence and cardiorespiratory fitness in large population studies. Mechanistic insights into these observations may strengthen the rationale for encouraging exercise fitness in the clinics for cancer prevention and may promote the development of new preventive strategies.
Recent findings
Studying the multifaceted activities of p53, a critical tumor suppressor gene, has revealed various cellular pathways necessary for adapting to environmental stresses. Genetic connections are being made between p53 and an increasing number of metabolic activities such as oxidative phosphorylation, glycolysis and fatty acid oxidation. In-vivo mouse models show that p53 plays an important role in determining both basal aerobic exercise capacity and its improvement by training.
Summary
The genetic pathways by which p53 regulates metabolism and exercise may help explain significant epidemiologic observations connecting cardiorespiratory fitness and cancer. Further understanding of these molecular pathways through human translational studies may promote the development of new cancer preventive strategies.
C1 [Wang, Ping-yuan; Zhuang, Jie; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Rm 5-5330, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
FU National Heart, Lung and Blood Institute (NHLBI)
FX This work was supported by the intramural program of National Heart,
Lung and Blood Institute (NHLBI).
NR 82
TC 16
Z9 16
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD JAN
PY 2012
VL 24
IS 1
BP 76
EP 82
DI 10.1097/CCO.0b013e32834de1d8
PG 7
WC Oncology
SC Oncology
GA 863GO
UT WOS:000298151000013
PM 22123233
ER
PT J
AU Merikangas, KR
Lamers, F
AF Merikangas, Kathleen R.
Lamers, Femke
TI The 'true' prevalence of bipolar II disorder
SO CURRENT OPINION IN PSYCHIATRY
LA English
DT Review
DE bipolar II disorder; epidemiology; hypomania
ID COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSIVE DISORDER; SUBTHRESHOLD
BIPOLARITY; MENTAL-DISORDERS; SPECTRUM; EPISODES; METAANALYSIS;
HYPOMANIA; ADULTS; MANIA
AB Purpose of review
Many studies - including meta-analyses - do not distinguish between bipolar I and II disorder. The aim of this study is to review the recent literature on the prevalence, correlates, consequences, and treatment patterns of bipolar II disorder.
Recent findings
In the past 2 years, several important studies have been conducted in the bipolar II field. The World Mental Health Survey initiative provides us with prevalence rate across 11 countries, while several meta-analyses on suicide and neurocognition directly compared bipolar I with bipolar II, informing us on the severe consequences of bipolar II disorder. Results from studies showed that the lifetime prevalence rate of bipolar II disorder in adults across 11 countries was 0.4%. Rates of bipolar II disorder in prospective studies of adolescents are substantially greater, with lifetime rates approaching 3-4%.
Summary
Evidence from these studies regarding comparable clinical consequences, patterns of comorbidity, suicide attempts, family history, and treatment patterns to bipolar I disorder document the validity of the bipolar II subtype.
C1 [Merikangas, Kathleen R.; Lamers, Femke] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Intramural Res Program, NIH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM Kathleen.Merikangas@nih.gov
RI Lamers, Femke/G-5161-2012
FU National Institute of Mental Health [1Z011Z01MH002870]; Netherlands
Organization for Scientific Research (NWO)
FX This study was funded by an intramural grant (1Z011Z01MH002870) from the
National Institute of Mental Health. F.L. is supported by a Rubicon
fellowship from the Netherlands Organization for Scientific Research
(NWO). The views and opinions expressed in this report are those of the
authors and should not be construed to represent the views of any of the
sponsoring organizations, agencies, or US Government.
NR 31
TC 20
Z9 23
U1 2
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7367
J9 CURR OPIN PSYCHIATR
JI Curr. Opin. Psychiatr.
PD JAN
PY 2012
VL 25
IS 1
BP 19
EP 23
DI 10.1097/YCO.0b013e32834de3de
PG 5
WC Psychiatry
SC Psychiatry
GA 863CS
UT WOS:000298141000004
PM 22156934
ER
PT J
AU Rebustini, IT
Hayashi, T
Reynolds, AD
Dillard, ML
Carpenter, EM
Hoffman, MP
AF Rebustini, Ivan T.
Hayashi, Toru
Reynolds, Andrew D.
Dillard, Melvin L.
Carpenter, Ellen M.
Hoffman, Matthew P.
TI miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr
during submandibular gland branching morphogenesis
SO DEVELOPMENT
LA English
DT Article
DE miR-200c; Vldlr; Salivary gland; Mouse
ID DENSITY LIPOPROTEIN RECEPTOR; EMBRYONIC STEM-CELLS; TO-MESENCHYMAL
TRANSITION; BREAST-CANCER CELLS; MICRORNA EXPRESSION; DOWN-REGULATION;
E-CADHERIN; PROSTATE-CANCER; GENE-EXPRESSION; SALIVARY-GLAND
AB The regulation of epithelial proliferation during organ morphogenesis is crucial for normal development, as dysregulation is associated with tumor formation. Non-coding microRNAs (miRNAs), such as miR-200c, are post-transcriptional regulators of genes involved in cancer. However, the role of miR-200c during normal development is unknown. We screened miRNAs expressed in the mouse developing submandibular gland (SMG) and found that miR-200c accumulates in the epithelial end buds. Using both loss- and gain-of-function, we demonstrated that miR-200c reduces epithelial proliferation during SMG morphogenesis. To identify the mechanism, we predicted miR-200c target genes and confirmed their expression during SMG development. We discovered that miR-200c targets the very low density lipoprotein receptor (Vldlr) and its ligand reelin, which unexpectedly regulate FGFR-dependent epithelial proliferation. Thus, we demonstrate that miR-200c influences FGFR-mediated epithelial proliferation during branching morphogenesis via a Vldlr-dependent mechanism. miR-200c and Vldlr may be novel targets for controlling epithelial morphogenesis during glandular repair or regeneration.
C1 [Rebustini, Ivan T.; Hayashi, Toru; Reynolds, Andrew D.; Dillard, Melvin L.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Carpenter, Ellen M.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM mhoffman@mail.nih.gov
FU National Institute of Dental and Craniofacial Research at the National
Institutes of Health
FX The study was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research at the National
Institutes of Health. Deposited in PMC for release after 12 months.
NR 124
TC 25
Z9 28
U1 1
U2 8
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JAN 1
PY 2012
VL 139
IS 1
BP 191
EP 202
DI 10.1242/dev.070151
PG 12
WC Developmental Biology
SC Developmental Biology
GA 864OJ
UT WOS:000298249200018
PM 22115756
ER
PT J
AU Brody, T
Yavatkar, AS
Kuzin, A
Kundu, M
Tyson, LJ
Ross, J
Lin, TY
Lee, CH
Awasaki, T
Lee, T
Odenwald, WF
AF Brody, Thomas
Yavatkar, Amarendra S.
Kuzin, Alexander
Kundu, Mukta
Tyson, Leonard J.
Ross, Jermaine
Lin, Tzu-Yang
Lee, Chi-Hon
Awasaki, Takeshi
Lee, Tzumin
Odenwald, Ward F.
TI Use of a Drosophila genome-wide conserved sequence database to identify
functionally related cis-regulatory enhancers
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE cis-regulatory enhancers; conserved sequence clusters (CSCs); Drosophila
melanogaster
ID SPLIT COMPLEX GENES; TRANSCRIPTION FACTOR; DNA-BINDING; DEVELOPMENTAL
ENHANCERS; NERVOUS-SYSTEM; POU-DOMAIN; ELEMENT; CNS; IDENTIFICATION;
SUPPRESSOR
AB Background: Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs. Results: We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization. Conclusions: cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process. Developmental Dynamics 241:169189, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Brody, Thomas; Kuzin, Alexander; Kundu, Mukta; Ross, Jermaine; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
[Yavatkar, Amarendra S.; Tyson, Leonard J.] NIH, Div Intramural Res, Informat Technol Program, Bethesda, MD 20892 USA.
[Lin, Tzu-Yang; Lee, Chi-Hon] NICHD, Sect Neuronal Connect, NIH, Bethesda, MD USA.
[Awasaki, Takeshi; Lee, Tzumin] HHMI, Ashburn, VA USA.
RP Brody, T (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM brodyt@ninds.nih.gov; ward@codon.nih.gov
RI Lee, Chi-Hon/G-9190-2012; Lin, Tzu-Yang/D-8300-2013
FU NIH, NINDS
FX Grant sponsor: Intramural Research Program of the NIH, NINDS.
NR 64
TC 7
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD JAN
PY 2012
VL 241
IS 1
SI SI
BP 169
EP 189
DI 10.1002/dvdy.22728
PG 21
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 862MW
UT WOS:000298097100015
PM 22174086
ER
PT J
AU Vijayakumar, A
Wu, YJ
Sun, H
Li, XS
Jeddy, Z
Liu, CY
Schwartz, GJ
Yakar, S
LeRoith, D
AF Vijayakumar, Archana
Wu, YingJie
Sun, Hui
Li, Xiaosong
Jeddy, Zuha
Liu, Chengyu
Schwartz, Gary J.
Yakar, Shoshana
LeRoith, Derek
TI Targeted Loss of GHR Signaling in Mouse Skeletal Muscle Protects Against
High-Fat Diet Induced Metabolic Deterioration
SO DIABETES
LA English
DT Article
ID GROWTH-HORMONE; ADIPOSE-TISSUE; IN-VIVO; BODY-COMPOSITION; INSULIN;
MICE; GLUCOSE; EXPRESSION; TRANSCRIPTION; ACTIVATION
AB Growth hormone (GH) exerts diverse tissue-specific metabolic effects that are not revealed by global alteration of GH action. To study the direct metabolic effects of GH in the muscle, we specifically inactivated the growth hormone receptor (ghr) gene in postnatal mouse skeletal muscle using the Cre/loxP system (mGHRKO model). The metabolic state of the mGHRKO mice was characterized under lean and obese states. High-fat diet feeding in the niGHRKO mice was associated with reduced adiposity, improved insulin sensitivity, lower systemic inflammation, decreased muscle and hepatic triglyceride content, and greater energy expenditure compared with control mice. The obese mGHRKO mice also had an increased respiratory exchange ratio, suggesting increased carbohydrate utilization. GH-regulated suppressor of cytokine signaling-2 (socs2) expression was decreased in obese mGHRKO mice. Interestingly, muscles of both lean and obese mGHRKO mice demonstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a possible mechanism whereby GHR signaling in muscle could affect liver and adipose tissue function. Thus, our study implicates skeletal muscle GHR signaling in mediating insulin resistance in obesity and, more importantly, reveals a novel role of muscle GHR signaling in facilitating cross-talk between muscle and other metabolic tissues. Diabetes 61:94-103, 2012
C1 [Vijayakumar, Archana; Wu, YingJie; Sun, Hui; Jeddy, Zuha; Yakar, Shoshana; LeRoith, Derek] Mt Sinai Sch Med, Dept Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Li, Xiaosong; Schwartz, Gary J.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Li, Xiaosong; Schwartz, Gary J.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA.
[Liu, Chengyu] NHLBI, Transgen Core Facil, NIH, Bethesda, MD USA.
RP LeRoith, D (reprint author), Mt Sinai Sch Med, Dept Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
EM sy1007@nyu.edu; derek.leroith@mssm.edu
FU National Institutes of Health NIH [DK-20541]
FX X.L. and G.J.S. are supported by the NIH DK-20541 grant from the
National Institutes of Health.
NR 46
TC 34
Z9 35
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JAN
PY 2012
VL 61
IS 1
BP 94
EP 103
DI 10.2337/db11-0814
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 871XZ
UT WOS:000298772300013
PM 22187377
ER
PT J
AU Thearle, MS
Muller, YL
Hanson, RL
Mullins, M
AbdusSamad, M
Tran, J
Knowler, WC
Bogardus, C
Krakoff, J
Baier, LJ
AF Thearle, Marie S.
Muller, Yunhua L.
Hanson, Robert L.
Mullins, Meghan
AbdusSamad, Maryam
Tran, John
Knowler, William C.
Bogardus, Clifton
Krakoff, Jonathan
Baier, Leslie J.
TI Greater Impact of Melanocortin-4 Receptor Deficiency on Rates of Growth
and Risk of Type 2 Diabetes During Childhood Compared With Adulthood in
Pima Indians
SO DIABETES
LA English
DT Article
ID GENE-MUTATIONS; OBESE CHILDREN; MORBID-OBESITY; PREVALENCE; ASSOCIATION;
POPULATION; VARIANTS; MELLITUS; SPECTRUM; COHORT
AB Features of melanocortin-4 receptor (MC4R) deficiency have been observed to be more pronounced in childhood. Longitudinal data from a population-based study were used to separate the phenotypic effects of MC4R deficiency during childhood and adulthood. The MC4R exon was sequenced in 6,760 individuals of predominantly Pima Indian heritage, and discovered mutations were functionally assessed in vitro. Effects on BMI, height, and slope of BMI change were assessed during childhood (ages 5-20 years) and adulthood (ages 20-45 years). Six mutations affecting MC4R function, including three that may be private to Pima Indians, were found in 159 individuals (2.4%). The slope of BMI increase was greater in individuals carrying an MC4R mutation compared with noncarriers during childhood but not during adulthood. The final adult height obtained was higher in individuals with MC4R deficiency. There was an increased risk for developing type 2 diabetes in individuals with a defective MC4R during childhood and adulthood, but this was only independent of BMI in childhood. The greater rates of body mass accumulation and risk of type 2 diabetes before the age of 20 years in individuals with MC4R deficiency indicate that the effects of these mutations are more apparent during the active growth of childhood. Diabetes 61:250-257, 2012
C1 [Thearle, Marie S.; Muller, Yunhua L.; Hanson, Robert L.; Mullins, Meghan; AbdusSamad, Maryam; Tran, John; Knowler, William C.; Bogardus, Clifton; Krakoff, Jonathan; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
RP Thearle, MS (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
EM thearlem@mail.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 36
TC 14
Z9 14
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JAN
PY 2012
VL 61
IS 1
BP 250
EP 257
DI 10.2337/db11-0708
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 871XZ
UT WOS:000298772300029
PM 22106157
ER
PT J
AU Turkbey, B
Bernardo, M
Merino, MJ
Wood, BJ
Pinto, PA
Choyke, PL
AF Tuerkbey, Baris
Bernardo, Marcelino
Merino, Maria J.
Wood, Bradford J.
Pinto, Peter A.
Choyke, Peter L.
TI MRI of localized prostate cancer: coming of age in the PSA era
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
DE prostate cancer; magnetic resonance imaging; prostate specific antigen
ID APPARENT DIFFUSION-COEFFICIENT; RADICAL RETROPUBIC PROSTATECTOMY; BEAM
RADIATION-THERAPY; CONTRAST-ENHANCED MRI; ACTIVE SURVEILLANCE;
ENDORECTAL MR; TRANSITION ZONE; 3 T; RECURRENCE; BIOPSY
AB Prostate cancer is the most common cancer among American men. It varies widely in aggressiveness, ranging from completely indolent to highly aggressive. Currently, predicting the natural history of a particular tumor and deciding on the appropriate treatment, which might include active surveillance, surgery, radiation or hormonal therapies, are based on the condition and age of the patient as well as the presumed stage of the disease. Imaging plays an important role in staging localized prostate cancer. Magnetic resonance imaging (MRI) best depicts the zonal anatomy, with a superior soft tissue resolution providing better results for tumor localization, monitoring, and local staging. Previously, the major function of prostate MRI has been in staging, and this role remains important. In this article, we introduce the reader to the expanding roles that MRI plays in the management of localized prostate cancer.
C1 [Tuerkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM bturkbey@yahoo.com
NR 66
TC 20
Z9 22
U1 0
U2 6
PU TURKISH SOC RADIOLOGY
PI ANKARA
PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY
SN 1305-3825
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD JAN-FEB
PY 2012
VL 18
IS 1
BP 34
EP 45
DI 10.4261/1305-3825.DIR.4478-11.1
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 872RZ
UT WOS:000298828300005
PM 21922459
ER
PT J
AU Turkbey, B
Aras, O
Karabulut, N
Turgut, AT
Akpinar, E
Alibek, S
Pang, YX
Erturk, SM
El Khouli, RH
Bluemke, DA
Choyke, PL
AF Turkbey, Baris
Aras, Omer
Karabulut, Nevzat
Turgut, Ahmet Tuncay
Akpinar, Erhan
Alibek, Sedat
Pang, Yuxi
Erturk, Sukru Mehmet
El Khouli, Riham H.
Bluemke, David A.
Choyke, Peter L.
TI Diffusion-weighted MRI for detecting and monitoring cancer: a review of
current applications in body imaging
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
DE cancer; diffusion weighted magnetic resonance imaging; body applications
ID UTERINE CERVICAL-CANCER; POSITRON-EMISSION-TOMOGRAPHY; URINARY-BLADDER
CARCINOMA; MALIGNANT HEPATIC-LESIONS; ADVANCED BREAST-CANCER;
CONTRAST-ENHANCED MRI; CELL LUNG-CANCER; PROSTATE-CANCER; LYMPH-NODES;
NEOADJUVANT CHEMOTHERAPY
AB Diffusion-weighted magnetic resonance imaging (MRI), Which involves the acquisition of a magnetic resonance signal related to the Brownian motion of water protons in tissue, has become a useful technique for assessing tumors. In this article, we review the basic concepts, imaging strategies, and body applications of diffusion-weighted MRI in detecting and monitoring cancer.
C1 [Turkbey, Baris; Aras, Omer; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Karabulut, Nevzat] Pamukkale Univ, Sch Med, Dept Radiol, Denizli, Turkey.
[Turgut, Ahmet Tuncay] Ankara Training & Educ Hosp, Dept Radiol, Ankara, Turkey.
[Akpinar, Erhan] Hacettepe Univ, Fac Med, Dept Radiol, TR-06100 Ankara, Turkey.
[Alibek, Sedat] Univ Erlangen Nurnberg, Inst Radiol, Erlangen, Germany.
[Pang, Yuxi] Philips Healthcare, Cleveland, OH USA.
[Erturk, Sukru Mehmet] Istanbul Sisli Etfal Training & Res Hosp, Dept Radiol, Istanbul, Turkey.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM bturkbey@yahoo.com
RI KARABULUT, Nevzat/A-8010-2014;
OI KARABULUT, Nevzat/0000-0002-0822-0281; Bluemke,
David/0000-0002-8323-8086
NR 141
TC 28
Z9 31
U1 1
U2 25
PU TURKISH SOC RADIOLOGY
PI ANKARA
PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY
SN 1305-3825
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD JAN-FEB
PY 2012
VL 18
IS 1
BP 46
EP 59
DI 10.4261/1305-3825.DIR.4708-11.2
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 872RZ
UT WOS:000298828300006
PM 21928189
ER
PT J
AU Lam, TTY
Ip, HS
Ghedin, E
Wentworth, DE
Halpin, RA
Stockwell, TB
Spiro, DJ
Dusek, RJ
Bortner, JB
Hoskins, J
Bales, BD
Yparraguirre, DR
Holmes, EC
AF Lam, Tommy Tsan-Yuk
Ip, Hon S.
Ghedin, Elodie
Wentworth, David E.
Halpin, Rebecca A.
Stockwell, Timothy B.
Spiro, David J.
Dusek, Robert J.
Bortner, James B.
Hoskins, Jenny
Bales, Bradley D.
Yparraguirre, Dan R.
Holmes, Edward C.
TI Migratory flyway and geographical distance are barriers to the gene flow
of influenza virus among North American birds
SO ECOLOGY LETTERS
LA English
DT Article
DE Avian influenza; ecological barriers; evolution; flyways; gene flow;
phylogeography; spatial distance
ID PATHOGENIC AVIAN INFLUENZA; WILD BIRDS; A VIRUSES; H5N1; EVOLUTION;
PHYLOGENIES; WATERFOWL; PATTERNS; PARAMYXOVIRUSES; TRANSMISSION
AB Despite the importance of migratory birds in the ecology and evolution of avian influenza virus (AIV), there is a lack of information on the patterns of AIV spread at the intra-continental scale. We applied a variety of statistical phylogeographic techniques to a plethora of viral genome sequence data to determine the strength, pattern and determinants of gene flow in AIV sampled from wild birds in North America. These analyses revealed a clear isolation-by-distance of AIV among sampling localities. In addition, we show that phylogeographic models incorporating information on the avian flyway of sampling proved a better fit to the observed sequence data than those specifying homogeneous or random rates of gene flow among localities. In sum, these data strongly suggest that the intra-continental spread of AIV by migratory birds is subject to major ecological barriers, including spatial distance and avian flyway.
C1 [Lam, Tommy Tsan-Yuk; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Ip, Hon S.; Dusek, Robert J.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI 53711 USA.
[Ghedin, Elodie] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA.
[Ghedin, Elodie; Halpin, Rebecca A.; Stockwell, Timothy B.; Spiro, David J.] J Craig Venter Inst, Rockville, MD 20850 USA.
[Wentworth, David E.] NYSDOH, Wadsworth Ctr, Albany, NY 12201 USA.
[Bortner, James B.; Hoskins, Jenny] US Fish & Wildlife Serv, Portland, OR 97232 USA.
[Dusek, Robert J.; Bales, Bradley D.] Oregon Dept Fish & Wildlife, Salem, OR 97303 USA.
[Yparraguirre, Dan R.] Calif Dept Fish & Game, Sacramento, CA 95814 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
RI Lam, Tommy Tsan-Yuk/D-4837-2012;
OI Wentworth, David/0000-0002-5190-980X; Dusek, Robert/0000-0001-6177-7479;
Holmes, Edward/0000-0001-9596-3552
FU National Institutes of Health [R01 GM080533]; US Department of the
Interior; US Fish and Wildlife Service; US Geological Survey, Biological
Resources Discipline; National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services [HHSN272200900007C]
FX This research was funded in part by grant R01 GM080533 from the National
Institutes of Health, by the US Department of the Interior and US Fish
and Wildlife Service's Avian Health Program, and by the US Geological
Survey, Biological Resources Discipline. We thank the US Fish and
Wildlife Service, as well as State and Tribal agencies. It was also in
part funded with federal funds from the National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Department of
Health and Human Services under contract numbers HHSN272200900007C. The
samples from the PF were collected under the 'Surveillance for Early
detection of Highly Pathogenic Avian Influenza H5N1 in Wild Migratory
Birds: a Strategy for the Pacific Flyway' Pacific Flyway Council, 2006.
We thank the field personnel who sampled birds throughout the flyway,
and gratefully acknowledge the contributions of many biologists who have
sequenced the influenza genomes published in GenBank. We also thank
members of the Diagnostic Virology Laboratory at the National Wildlife
Health Center, especially Katy Griffin, Jessica Montez, Samantha Scott
and Kim Kooiman. Additional bioinformatic and computational resources
were provided by the Computer Centre at The University of Hong Kong
(HKU) and TWGrid in Taiwan. We also thank W. K. Kwan and Frankie Cheung
(HKU) for technical support. Any use of trade, product, or firm names is
for descriptive purposes only and does not imply endorsement by the US
government.
NR 46
TC 43
Z9 44
U1 2
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1461-023X
J9 ECOL LETT
JI Ecol. Lett.
PD JAN
PY 2012
VL 15
IS 1
BP 24
EP 33
DI 10.1111/j.1461-0248.2011.01703.x
PG 10
WC Ecology
SC Environmental Sciences & Ecology
GA 856KC
UT WOS:000297637800004
PM 22008513
ER
PT J
AU Chowell, G
Viboud, C
Simonsen, L
Miller, MA
Acuna-Soto, R
Diaz, JMO
Martinez-Martin, AF
AF Chowell, Gerardo
Viboud, Cecile
Simonsen, Lone
Miller, Mark A.
Acuna-Soto, Rodolfo
Ospina Diaz, Juan M.
Fernando Martinez-Martin, Abel
TI The 1918-19 Influenza Pandemic in Boyaca, Colombia
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID SPANISH INFLUENZA; REPRODUCTION NUMBER; MORTALITY IMPACT; H1N1
INFLUENZA; TRANSMISSIBILITY; WAVE; CIRCULATION; EPIDEMICS; PATTERNS;
CITY
AB To quantify age-specific excess-mortality rates and transmissibility patterns for the 1918-20 influenza pandemic in Boyaca, Colombia, we reviewed archival mortality records. We identified a severe pandemic wave during October 1918-January1919 associated with 40 excess deaths per 10,000 population. The age profile for excess deaths was W shaped; highest mortality rates were among infants (<5 y of age), followed by elderly persons (>= 60 y) and young adults (25-29 y). Mean reproduction number was estimated at 1.4-1.7, assuming 3- or 4-day generation intervals. Boyaca, unlike cities in Europe, the United States, or Mexico, experienced neither a herald pandemic wave of deaths early in 1918 nor a recrudescent wave in 1920. In agreement with reports from Mexico, our study found no death-sparing effect for elderly persons in Colombia. We found regional disparities in prior immunity and timing of introduction of the 1918 pandemic virus across populations.
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85282 USA.
[Chowell, Gerardo] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Washington, DC USA.
[Acuna-Soto, Rodolfo] Univ Nacl Autonoma Mexico, Delegacion Coyoacan, Mexico.
[Ospina Diaz, Juan M.; Fernando Martinez-Martin, Abel] Univ Pedag & Tecnol Colombia, Boyaca, Colombia.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Box 872402, Tempe, AZ 85282 USA.
EM gchowell@asu.edu
RI Chowell, Gerardo/F-5038-2012;
OI Chowell, Gerardo/0000-0003-2194-2251; Martinez Martin, Abel
Fernando/0000-0002-4621-6072; Simonsen, Lone/0000-0003-1535-8526
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center; Office of Global Affairs, International
Influenza Unit, in the Office of the Secretary of the Department of
Health and Human Services
FX This research was conducted in the context of the Multinational
Influenza Seasonal Mortality Study, which is an ongoing international
collaborative effort for understanding influenza epidemiological and
evolutionary patterns, and which is led by the Fogarty International
Center, National Institutes of Health (www.origem.info/misms/index.php).
Funding for this project comes in part (to L.S.) from the Research and
Policy for Infectious Disease Dynamics program of the Science and
Technology Directorate, Department of Homeland Security and Fogarty
International Center, and from the Office of Global Affairs,
International Influenza Unit, in the Office of the Secretary of the
Department of Health and Human Services.
NR 40
TC 10
Z9 10
U1 2
U2 7
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JAN
PY 2012
VL 18
IS 1
BP 48
EP 56
DI 10.3201/eid1801.101969
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 874QK
UT WOS:000298973000007
PM 22257780
ER
PT J
AU Liu, Y
Poon, V
Sanchez-Watts, G
Watts, AG
Takemori, H
Aguilera, G
AF Liu, Ying
Poon, Victoria
Sanchez-Watts, Graciela
Watts, Alan G.
Takemori, Hiroshi
Aguilera, Greti
TI Salt-Inducible Kinase Is Involved in the Regulation of
Corticotropin-Releasing Hormone Transcription in Hypothalamic Neurons in
Rats
SO ENDOCRINOLOGY
LA English
DT Article
ID MEDIATED GENE-EXPRESSION; BINDING PROTEIN-ACTIVITY; PARAVENTRICULAR
NUCLEUS; CEREBROSPINAL-FLUID; RESPONSIVE ELEMENT; CREB ACTIVITY; SIK;
CORTICOSTERONE; STAUROSPORINE; ACTIVATION
AB Activation of CRH transcription requires phosphorylation of cAMP response element-binding protein (CREB) and translocation of the CREB coactivator, transducer of regulated CREB activity (TORC) from cytoplasm to nucleus. In basal conditions, transcription is low because TORC remains in the cytoplasm, inactivated by phosphorylation through Ser/Thr protein kinases of the AMP-dependent protein kinases (AMPK) family, including salt-inducible kinase (SIK). To determine which kinase is responsible for TORC phosphorylation in CRH neurons, we measured SIK1 and SIK2 mRNA in the hypothalamic paraventricular nucleus of rats by in situ hybridization. In basal conditions, low mRNA levels of the two kinases were found in the dorsomedial paraventricular nucleus, consistent with location in CRH neurons. One hour of restraint stress increased SIK1 mRNA levels, whereas SIK2 mRNA showed only minor increases. In 4B hypothalamic neurons, or primary cultures, SIK1 mRNA (but not SIK2 mRNA) was inducible by the cAMP stimulator, forskolin. Overexpression of either SIK1 or SIK2 in 4B cells reduced nuclear TORC2 levels (Western blot) and inhibited forskolin-stimulated CRH transcription (luciferase assay). Conversely, the nonselective SIK inhibitor, staurosporine, increased nuclear TORC2 content and stimulated CRH transcription in 4Bcells and primary neuronal cultures (heteronuclear RNA). Unexpectedly, in 4B cells specific short hairpin RNA knockdown of endogenous SIK2 but not SIK1 induced nuclear translocation of TORC2 and CRH transcription, suggesting that SIK2 mediates TORC inactivation in basal conditions, whereas induction of SIK1 limits transcriptional activation. The study provides evidence that SIK represses CRH transcription by inactivating TORC, providing a potential mechanism for rapid on/off control of CRH transcription. (Endocrinology 153: 223-233, 2012)
C1 [Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
[Sanchez-Watts, Graciela; Watts, Alan G.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Takemori, Hiroshi] Natl Inst Biomed Innovat, Lab Cell Signaling & Metab Dis, Osaka 5670085, Japan.
RP Aguilera, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,Program Dev Endocrinol & Genet, Bldg 10,CRC,Room 1E-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
FU National Institutes of Health/Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Institute of
Neurological Disorders and Stroke [NS029728]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health/Eunice Kennedy Shriver National Institute
of Child Health and Human Development (to G. A.), and the National
Institute of Neurological Disorders and Stroke Grant NS029728 (to
A.G.W.).
NR 36
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U1 1
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JAN
PY 2012
VL 153
IS 1
BP 223
EP 233
DI 10.1210/en.2011-1404
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 869XC
UT WOS:000298631500021
PM 22109884
ER
PT J
AU VanderWeele, TJ
Mumford, SL
Schisterman, EF
AF VanderWeele, Tyler J.
Mumford, Sunni L.
Schisterman, Enrique F.
TI Conditioning on Intermediates in Perinatal Epidemiology
SO EPIDEMIOLOGY
LA English
DT Article
ID BIRTH-WEIGHT PARADOX; INFANT-MORTALITY; PRINCIPAL STRATIFICATION;
SENSITIVITY-ANALYSIS; PLACENTAL ABRUPTION; MEDIATION ANALYSIS;
CEREBRAL-PALSY; PRETERM BIRTH; UNITED-STATES; BIAS
AB It is common practice in perinatal epidemiology to calculate gestational-age-specific or birth-weight-specific associations between an exposure and a perinatal outcome. Gestational age or birth weight, for example, might lie on a pathway from the exposure to the outcome. This practice of conditioning on a potential intermediate has come under critique for various reasons. First, if one is interested in assessing the overall effect of an exposure on an outcome, it is not necessary to stratify, and indeed, it is important not to stratify, on an intermediate. Second, if one does condition on an intermediate, to try to obtain what might conceived of as a "direct effect" of the exposure on the outcome, then various biases and paradoxical results can arise. It is now well documented theoretically and empirically that, when there is an unmeasured common cause of the intermediate and the outcome, associations adjusted for the intermediate are subject to bias. In this paper, we propose 3 approaches to facilitate valid inference when effects conditional on an intermediate are in view. These 3 approaches correspond to (i) conditioning on the predicted risk of the intermediate, (ii) conditioning on the intermediate itself in conjunction with sensitivity analysis, and (iii) conditioning on the subgroup of individuals for whom the intermediate would occur irrespective of the exposure received. The second and third approaches both require sensitivity analysis, and they result in a range of estimates. Each of the 3 approaches can be used to resolve the "birth-weight paradox" that exposures such as maternal smoking seem to have a protective effect among low-birth-weight infants. The various methodologic approaches described in this paper are applicable to a number of similar settings in perinatal epidemiology.
C1 [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA.
RP VanderWeele, TJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM tvanderw@hsph.harvard.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU National Institutes of Health [HD060696]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health
FX Supported by National Institutes of Health grant HD060696 (to T.J.V.)
and Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health (to S. L. M. and E. F. S.). The authors reported no other
financial interests related to this research.
NR 42
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U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JAN
PY 2012
VL 23
IS 1
BP 1
EP 9
DI 10.1097/EDE.0b013e31823aca5d
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 863IU
UT WOS:000298156800001
PM 22157298
ER
PT J
AU VanderWeele, TJ
Mumford, SL
Schisterman, EF
AF VanderWeele, Tyler J.
Mumford, Sunni L.
Schisterman, Enrique F.
TI Choosing Effect Measures "If I Only Had a ... "
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID BIRTH-WEIGHT PARADOX
C1 [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA.
RP VanderWeele, TJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM tvanderw@hsph.harvard.edu
NR 7
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JAN
PY 2012
VL 23
IS 1
BP 13
EP 14
DI 10.1097/EDE.0b013e31823b6990
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 863IU
UT WOS:000298156800003
ER
PT J
AU Alonso, WJ
Acuna-Soto, R
Giglio, R
Nuckols, J
Leyk, S
Schuck-Paim, C
Viboud, C
Miller, MA
McCormick, BJJ
AF Alonso, W. J.
Acuna-Soto, R.
Giglio, R.
Nuckols, J.
Leyk, S.
Schuck-Paim, C.
Viboud, C.
Miller, M. A.
McCormick, B. J. J.
TI Spatio-temporal patterns of diarrhoeal mortality in Mexico
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Climate; diarrhoea; Mexico; mortality; seasonality
ID ROTAVIRUS ACTIVITY; UNITED-STATES; ENTERIC DISEASES; TEMPORAL TRENDS;
RISK-FACTORS; CHILDREN; BACTERIAL; VIETNAM; IMPACT; BRAZIL
AB Diarrhoeal mortality rates in Mexican children dramatically declined during the 1980s and 1990s, concomitant with a temporal shift in peak deaths from summer to autumn-winter. The spatial dynamics of these patterns have not previously been studied. We first describe the seasonal features of paediatric diarrhoeal mortality in Mexico as a whole, then across individual states. While no geographical gradients in the magnitude of diarrhoeal mortality rates have been detected in recent years, we identified a distinct spatial pattern in the timing of peak mortality rate. In the 1980s the summer peak mortality was earliest around Mexico's capital and later in states to the southeast and northwest. Our results suggest that the direction and timing of those annual waves are related to the mean monthly precipitation and mean daily temperature. This pattern has disintegrated in recent years as the summer peak has diminished.
C1 [Alonso, W. J.; Nuckols, J.; Leyk, S.; Viboud, C.; Miller, M. A.; McCormick, B. J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Acuna-Soto, R.] Univ Nacl Autonoma Mexico, Sch Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico.
[Giglio, R.] Univ Fed Santa Catarina, Dept Econ, BR-88040900 Florianopolis, SC, Brazil.
[Leyk, S.] Univ Colorado, Dept Geog, Boulder, CO 80309 USA.
RP McCormick, BJJ (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM ben.mccormick@nih.gov
FU Bill and Melinda Gates Foundation; Fogarty International Center of the
National Institutes of Health as part of the Mal-ED network
FX We thank Dr Jaime Sepulveda and Dr Rafael Solano for kindly providing
the mortality data and Dr Laura J. Ninger and Christine Jessup or their
useful comments on the manuscript. This study was funded by the Bill and
Melinda Gates Foundation and the Fogarty International Center of the
National Institutes of Health as part of the Mal-ED network.
NR 33
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Z9 7
U1 0
U2 11
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JAN
PY 2012
VL 140
IS 1
BP 91
EP 99
DI 10.1017/S0950268811000562
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 868TC
UT WOS:000298547400012
PM 21489339
ER
PT J
AU Kim, I
Kim, YJ
Metais, JY
Dunbar, CE
Larochelle, A
AF Kim, Inho
Kim, Yoo-Jin
Metais, Jean-Yves
Dunbar, Cynthia E.
Larochelle, Andre
TI Transient silencing of PTEN in human CD34(+) cells enhances their
proliferative potential and ability to engraft immunodeficient mice
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; MARROW REPOPULATING CELLS; GENE-TRANSFER;
SELF-RENEWAL; CYCLE ENTRY; TRANSDUCTION; VECTORS
AB The ability to expand hematopoietic stem and progenitor cells (HSPCs) in vitro will enhance the success of a wide range of transplant-related therapies. PTEN (phosphatase and tensin homologue deleted on chromosome 10) has been implicated as a regulator of murine HSPC self-renewal, but little is understood about the role of PTEN in human HSPC regulation. We tested the impact of transient small interfering RNA (siRNA) induced inhibition of PTEN expression in human CD34(+) cells on their cell cycle profile, their susceptibility to retroviral transduction, and their ability to self-renew and repopulate nonobese diabetic/severe combined immunodeficiency disease with interleukin-2 receptor gamma-chain deficiency mice. Reduced PTEN messenger RNA and protein levels were confirmed in PTEN siRNA-treated CD34(+) cells compared with control siRNA-treated CD34(+) cells. Transient silencing of PTEN in CD34(+) cells promoted their entry into cell cycle, and increased their expansion in vitro compared with control siRNA-treated CD34(+) cells. When these cells were transduced with retroviral vectors, transduction efficiencies in the bulk CD34(+) cells transfected with PTEN siRNA were significantly higher compared with CD34(+) cells transfected with a control siRNA. Transient PTEN suppression in CD34(+) cells also increased their proliferation and engraftment potential in nonobese diabetic/severe combined immunodeficiency disease with interleukin-2 receptor gamma-chain deficiency mice, and maintained their multilineage differentiation capacity in vivo. No mice developed myeloproliferative disorders or leukemias. Similar to findings with murine HSPC, PTEN may also promote quiescence of human HSPC. With optimization of technologies for transfer of siRNA in primary CD34(+) cells, this approach may facilitate investigations into the mechanisms underlying HSPC self-renewal, and could find clinical applications in gene therapy protocols. Published by Elsevier Inc. on behalf of the ISEH - Society for Hematology and Stem Cells.
C1 [Dunbar, Cynthia E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Room 4E-5132,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
RI Kim, In Ho/J-5428-2012
FU National Heart, Lunch, and Blood Institute of the National Institutes of
Health
FX We thank Dr. David Stroncek and the Department of Transfusion Medicine
staff for the apheresis and CD34+ cell selection from healthy
donors. The gammaretrovirus vectors used in this study, MND.MFG.YFP c10
were a gift from Dr. Hans-Peter Kiem. We are also grateful to Keyvan
Keyvanfar from the Hematology Branch flow facility for his assistance
with flow sorting and analysis. This work was supported by the
intramural research programs of the National Heart, Lunch, and Blood
Institute (C.E.D.) of the National Institutes of Health.
NR 18
TC 11
Z9 11
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD JAN
PY 2012
VL 40
IS 1
BP 84
EP 91
DI 10.1016/j.exphem.2011.10.001
PG 8
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 865VG
UT WOS:000298338400008
PM 22019626
ER
PT J
AU Goldstein, AL
Hannappel, E
Sosne, G
Kleinman, HK
AF Goldstein, Allan L.
Hannappel, Ewald
Sosne, Gabriel
Kleinman, Hynda K.
TI Thymosin beta(4): a multi-functional regenerative peptide. Basic
properties and clinical applications
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE apoptosis; inflammation; migration; regeneration; scar formation; stem
cells; thymosin beta(4); tissue repair
ID CORNEAL EPITHELIAL-CELLS; DEOXYNUCLEOTIDYL TRANSFERASE-ACTIVITY;
ASPARTYL-LYSYL-PROLINE; IN-VITRO; INFLAMMATORY MEDIATORS;
MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS; SYNTHETIC PEPTIDE;
GENE-EXPRESSION; CARDIAC REPAIR
AB Introduction: Thymosin beta(4), a low molecular weight, naturally-occurring peptide plays a vital role in the repair and regeneration of injured cells and tissues. After injury, thymosin beta(4), is released by platelets, macrophages and many other cell types to protect cells and tissues from further damage and reduce apoptosis, inflammation and microbial growth. Thymosin beta(4) binds to actin and promotes cell migration, including the mobilization, migration, and differentiation of stem/progenitor cells, which form new blood vessels and regenerate the tissue. Thymosin beta(4) also decreases the number of myofibroblasts in wounds, resulting in decreased scar formation and fibrosis
Areas covered: This article will cover the many thymosin beta(4) activities that directly affect the repair and regeneration cascade with emphasis on its therapeutic uses and potential. Our approach has been to evaluate the basic biology of the molecule as well as its potential for clinical applications in the skin, eye, heart and brain.
Expert opinion: The considerable advances in our understanding of the functional biology and mechanisms of action of thymosin beta(4) have provided the scientific foundation for ongoing and projected clinical trials in the treatment of dermal wounds, corneal injuries and in the regeneration and repair of heart and CNS tissue following ischemic insults and trauma.
C1 [Goldstein, Allan L.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Hannappel, Ewald] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany.
[Sosne, Gabriel] Wayne State Univ, Sch Med, Dept Ophthalmol & Anat Cell Biol, Detroit, MI USA.
[Kleinman, Hynda K.] NIDCR, NIH, Bethesda, MD 20892 USA.
RP Goldstein, AL (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, 2300 I St NW, Washington, DC 20037 USA.
EM bcmalg@gwumc.edu
FU RegeneRx Biopharmaceuticals, Inc.
FX AL Goldstein is founder and Chairman of the Board and Chief Scientific
Advisor of RegeneRx Biopharmaceuticals, Inc. and owns shares of stock in
the company. HK Kleinman is a paid consultant for RegeneRx
Biopharmaceuticals, Inc. and is a member of their Scientific Advisory
Board and does not own any stock. G Sosne and E Hannappel are non-paid
members of the Scientific Advisory Board of RegeneRx Biopharmaceuticals,
Inc. and does not own any stock.
NR 97
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Z9 52
U1 1
U2 22
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD JAN
PY 2012
VL 12
IS 1
BP 37
EP 51
DI 10.1517/14712598.2012.634793
PG 15
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 863TK
UT WOS:000298190700004
PM 22074294
ER
PT J
AU Lazarus, LH
Okada, Y
AF Lazarus, Lawrence H.
Okada, Yoshio
TI Engineering endomorphin drugs: state of the art
SO EXPERT OPINION ON THERAPEUTIC PATENTS
LA English
DT Review
DE agonists; antagonists; endomorphins; opioid receptors; peptide
synthesis; rational drug design
ID MU-OPIOID RECEPTOR; RANDOMIZED CONTROLLED-TRIALS; BLOOD-BRAIN-BARRIER;
SPINAL-CORD; IN-VITRO; MORPHINE-TOLERANCE; ENDOGENOUS LIGANDS;
SUBSTANCE-P; ANTINOCICEPTIVE ACTIVITY; PEPTIDES ENDOMORPHIN-1
AB Introduction: Although endomorphins-1 (EM-1; H-Tyr-Pro-Phe-Trp-NH2) and -2 (EM-2; H-Tyr-Pro-Phe-Phe-NH2) are primarily considered agonists for the mu-opioid receptor (MOR), systematic alterations to specific residues provided antagonists and ligands with mixed mu/delta-opioid properties, suitable for application to health-related topics. While the application of endomorphins as anti-nociceptive agents and numerous biological endpoints were experimentally delineated in laboratory animals and in vitro, clinical use is currently absent. However, structural alterations provide enhanced stability; formation of MOR antagonists or mixed and dual mu/delta-acting ligands could find considerable therapeutic potential.
Areas covered: This review attempts to succinctly provide insight on the development and bioactivity of endomorphin analogues during the past decade. Rational design approaches will focus on the engineering of endomorphin agonists, antagonists and mixed ligands for their application as a multi-target ligand.
Expert opinion: Aside from alleviating pain, EM analogues open new horizons in the treatment of medical syndromes involving neural reward mechanisms and extraneural regulation effects on homeostasis. Highly selective MOR antagonists may be promising to reduce inflammation, attenuate addiction to drugs and excess consumption of high-caloric food, ameliorate alcoholism, affect the immune system and combat opioid bowel dysfunction.
C1 [Lazarus, Lawrence H.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Okada, Yoshio] Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan.
RP Lazarus, LH (reprint author), NIEHS, Lab Toxicol & Pharmacol, 111 S TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM lazarus@niehs.nih.gov
FU NIH; NIEHS
FX The authors appreciate the consistent and professional support of
Stephanie Holmgren, MLA, Library Information Services Branch, NIEHS, our
numerous former colleagues the world over, Dr. Hiroaki Taguichi, Suzuka
University of Medical Science, Mie, Japan, for preparing the scheme on
the synthesis of 1,5-enediaol EM-2 analogues, and in part to the
Intramural Research Program of the NIH and NIEHS.
NR 149
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U1 2
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3776
J9 EXPERT OPIN THER PAT
JI Expert Opin. Ther. Patents
PD JAN
PY 2012
VL 22
IS 1
BP 1
EP 14
DI 10.1517/13543776.2012.646261
PG 14
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 873DD
UT WOS:000298860200001
PM 22214283
ER
PT J
AU Monaco, MCG
Major, EO
AF Monaco, Maria Chiara G.
Major, Eugene O.
TI The link between VLA-4 and JC virus reactivation
SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY
LA English
DT Review
DE adhesion molecules; CNS; JCV; multiple sclerosis; natalizumab;
progressive multifocal leukoencephalopathy; reactivation; treatment;
VLA-4
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RECONSTITUTION INFLAMMATORY
SYNDROME; PEDIATRIC MULTIPLE-SCLEROSIS; B-CELL DEPLETION; HEMATOPOIETIC
PROGENITOR CELLS; NATALIZUMAB-TREATED PATIENTS; CENTRAL-NERVOUS-SYSTEM;
HIV-NEGATIVE PATIENTS; BLOOD-BRAIN-BARRIER; ADVERSE DRUG EVENTS
AB Natalizumab represents an effective biological therapy to treat relapsing-remitting forms of multiple sclerosis and Crohn's disease by blocking the migration of inflammatory cells to the brain and gut. Natalizumab, however, is associated with a risk of progressive multifocal leukoencephalopathy (PML) caused by the reactivation of JC virus. The emergence of PML in this setting has moved PML from being a rare disease mostly seen in HIV-infected individuals to become an important cause of complications in patients receiving immunomodulatory treatments. The incidence of PML associated with natalizumab treatment is approximately 1.5:750, but this increases to approximately 1: 100 in patients after 24-36 doses based on available estimates of individuals who have a prior history of immunosuppressive treatment and are antibody positive to JC virus. Natalizumab treatment has raised questions about the pathogenesis of PML but also has provided the opportunity to investigate sites of virus latency and mechanisms of trafficking to the brain.
C1 [Monaco, Maria Chiara G.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
EM majorg@ninds.nih.gov
NR 104
TC 8
Z9 8
U1 0
U2 1
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1744-666X
J9 EXPERT REV CLIN IMMU
JI Expert Rev. Clin. Immunol.
PD JAN
PY 2012
VL 8
IS 1
BP 63
EP 72
DI 10.1586/ECI.11.85
PG 10
WC Immunology
SC Immunology
GA 874NO
UT WOS:000298965500016
PM 22149341
ER
PT J
AU Gurumurthy, M
Mukherjee, T
Dowd, CS
Singh, R
Niyomrattanakit, P
Tay, JA
Nayyar, A
Lee, YS
Cherian, J
Boshoff, HI
Dick, T
Barry, CE
Manjunatha, UH
AF Gurumurthy, Meera
Mukherjee, Tathagata
Dowd, Cynthia S.
Singh, Ramandeep
Niyomrattanakit, Pornwaratt
Tay, Jo Ann
Nayyar, Amit
Lee, Yong Sok
Cherian, Joseph
Boshoff, Helena I.
Dick, Thomas
Barry, Clifton E., III
Manjunatha, Ujjini H.
TI Substrate specificity of the deazaflavin-dependent nitroreductase from
Mycobacterium tuberculosis responsible for the bioreductive activation
of bicyclic nitroimidazoles
SO FEBS JOURNAL
LA English
DT Article
DE F420; mycobacterium; nitroimidazole; PA-824; tuberculosis
ID COENZYME F-420; ANTITUBERCULAR ACTIVITY; BOVIS BCG; PA-824; DRUG;
METRONIDAZOLE; ANALOGS; IDENTIFICATION; BIOSYNTHESIS; NO
AB The bicyclic 4-nitroimidazoles PA-824 and OPC-67683 represent a promising novel class of therapeutics for tuberculosis and are currently in phase II clinical development. Both compounds are pro-drugs that are reductively activated by a deazaflavin (F(420)) dependent nitroreductase (Ddn). Herein we describe the biochemical properties of Ddn including the optimal enzymatic turnover conditions and substrate specificity. The preference of the enzyme for the (S) isomer of PA-824 over the (R) isomer is directed by the presence of a long hydrophobic tail. Nitroimidazo-oxazoles bearing only short alkyl substituents at the C-7 position of the oxazole were reduced by Ddn without any stereochemical preference. However, with bulkier substitutions on the tail of the oxazole, Ddn displayed stereospecificity. Ddn mediated metabolism of PA-824 results in the release of reactive nitrogen species. We have employed a direct chemiluminescence based nitric oxide (NO) detection assay to measure the kinetics of NO production by Ddn. Binding affinity of PA-824 to Ddn was monitored through intrinsic fluorescence quenching of the protein facilitating a turnover-independent assessment of affinity. Our results indicate that (R)-PA-824, despite not being turned over by Ddn, binds to the enzyme with the same affinity as the active (S) isomer. This result, in combination with docking studies in the active site, suggests that the (R) isomer probably has a different binding mode than the (S) with the C-3 of the imidazole ring orienting in a non-productive position with respect to the incoming hydride from F(420). The results presented provide insight into the biochemical mechanism of reduction and elucidate structural features important for understanding substrate binding.
C1 [Gurumurthy, Meera; Niyomrattanakit, Pornwaratt; Tay, Jo Ann; Cherian, Joseph; Dick, Thomas; Manjunatha, Ujjini H.] Novartis Inst Trop Dis, Singapore 138670, Singapore.
[Mukherjee, Tathagata; Dowd, Cynthia S.; Singh, Ramandeep; Nayyar, Amit; Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
[Lee, Yong Sok] Ctr Informat Technol, NIH, Ctr Mol Modeling, Bethesda, MD USA.
RP Manjunatha, UH (reprint author), Novartis Inst Trop Dis, 10 Biopolis Rd, Singapore 138670, Singapore.
EM cbarry@niaid.nih.gov; manjunatha.ujjini@novartis.com
RI Barry, III, Clifton/H-3839-2012; Cherian, Joseph/Q-2522-2016
FU Bill and Melinda Gates Foundation; Wellcome Trust [11]; NITD; NIAID;
Center for Information Technology
FX This work was funded, in part, by a grant from the Bill and Melinda
Gates Foundation and the Wellcome Trust through the Grand Challenges in
Global Health Program 11 to NITD through Imperial College London; by
NITD and also in part by the intramural research program of NIAID (to
CEB) and through the Center for Information Technology (to YSL). We
thank Lacy Daniels for F420-2. The quantum chemical study
utilized PC/LINUX clusters at the Center for Molecular Modeling of the
NIH (http://cit.nih.gov).
NR 41
TC 25
Z9 26
U1 0
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JAN
PY 2012
VL 279
IS 1
BP 113
EP 125
DI 10.1111/j.1742-4658.2011.08404.x
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 862AY
UT WOS:000298063400012
PM 22023140
ER
PT J
AU Patacsil, D
Osayi, S
Tran, AT
Saenz, F
Yimer, L
Shajahan, AN
Gokhale, PC
Verma, M
Clarke, R
Chauhan, SC
Kumar, D
AF Patacsil, Dorrelyn
Osayi, Sylvester
Anh Thu Tran
Saenz, Francisco
Yimer, Lydia
Shajahan, Ayesha N.
Gokhale, Prafulla C.
Verma, Mukesh
Clarke, Robert
Chauhan, Subhash C.
Kumar, Deepak
TI Vitamin E succinate inhibits survivin and induces apoptosis in
pancreatic cancer cells
SO GENES AND NUTRITION
LA English
DT Article
DE Vitamin E; Vitamin E succinate; Survivin; Pancreatic cancer; Apoptosis
ID ALPHA-TOCOPHERYL SUCCINATE; MDA-MB-435 CELLS; TUMOR-GROWTH; EXPRESSION;
INDUCTION; PROTEINS; MOLECULE; ANALOGS; BCL-2
AB Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Identifying novel chemotherapeutic and chemopreventive approaches is critical in the prevention and treatment of cancers such as pancreatic cancer. Vitamin E succinate (VES) is a redox-silent analog of the fat-soluble vitamin alpha-tocopherol. In the present study, we explored the antiproliferative action of VES and its effects on inhibitor of apoptosis proteins in pancreatic cancer cells. We show that VES inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. Further, we demonstrate that VES downregulates the expression of survivin and X-linked inhibitor of apoptosis proteins. The apoptosis induced by VES was augmented by siRNA-mediated inhibition of survivin in PANC-1 cells. In summary, our results suggest that VES targets survivin signaling and induces apoptosis in pancreatic cancer cells.
C1 [Patacsil, Dorrelyn; Osayi, Sylvester; Anh Thu Tran; Saenz, Francisco; Yimer, Lydia; Kumar, Deepak] Univ Dist Columbia, Canc Res Lab, Dept Biol & Environm Sci, Washington, DC 20008 USA.
[Shajahan, Ayesha N.; Gokhale, Prafulla C.; Clarke, Robert; Kumar, Deepak] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Chauhan, Subhash C.] Sanford Res Univ S Dakota, Canc Biol Res Ctr, Sioux Falls, SD 57105 USA.
RP Kumar, D (reprint author), Univ Dist Columbia, Canc Res Lab, Dept Biol & Environm Sci, Bldg 44,Room 312,4200 Connecticut Ave NW, Washington, DC 20008 USA.
EM dkumar@udc.edu
RI Clarke, Robert/A-6485-2008;
OI Clarke, Robert/0000-0002-9278-0854; Osayi, Sylvester/0000-0001-8863-6975
FU NCI UDC-LCCC [U56]; USDA/UDC Agricultural Experiment Station; MBRS
SCORE/SC1; NSF-HBCU-UP
FX The studies were conducted using the Tissue Culture and Flow Cytometry
and Cell Sorting Shared Resources of the Lombardi Comprehensive Cancer
Center. We thank Karen Creswell for providing excellent technical
assistance. Pilot funding from NCI UDC-LCCC U56 (DK, RC), USDA/UDC
Agricultural Experiment Station (DK), MBRS SCORE/SC1 (DK), NSF-HBCU-UP
fellowship (SO, AT, LY).
NR 22
TC 8
Z9 9
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1555-8932
J9 GENES NUTR
JI Genes Nutr.
PD JAN
PY 2012
VL 7
IS 1
SI SI
BP 83
EP 89
DI 10.1007/s12263-011-0242-x
PG 7
WC Genetics & Heredity; Nutrition & Dietetics
SC Genetics & Heredity; Nutrition & Dietetics
GA 872KQ
UT WOS:000298808700010
PM 21842182
ER
PT J
AU Fagundes, CP
Bennett, JM
Alfano, CM
Glaser, R
Povoski, SP
Lipari, AM
Agnese, DM
Yee, LD
Carson, WE
Farrar, WB
Malarkey, WB
Chen, M
Kiecolt-Glaser, JK
AF Fagundes, Christopher P.
Bennett, Jeanette M.
Alfano, Catherine M.
Glaser, Ronald
Povoski, Stephen P.
Lipari, Adele M.
Agnese, Doreen M.
Yee, Lisa D.
Carson, William E., III
Farrar, William B.
Malarkey, William B.
Chen, Min
Kiecolt-Glaser, Janice K.
TI Social Support and Socioeconomic Status Interact to Predict Epstein-Barr
Virus Latency in Women Awaiting Diagnosis or Newly Diagnosed With Breast
Cancer
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE socioeconomic status; cellular immunity; cancer survivorship;
psychoneuroimmunology; psycho-oncology
ID INSOMNIA SEVERITY INDEX; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; HEALTH;
VALIDATION; DEPRESSION; STRESS; FAMILY; CYTOMEGALOVIRUS; MORTALITY
AB Objective: Both higher socioeconomic status (SES) and supportive personal relationships confer health benefits, including better immune function. This study assessed the joint impact of SES and social support on the expression of a latent herpesvirus, Epstein-Barr virus (EBV), in a group of highly stressed women. Methods: Two-hundred and twenty four women either awaiting further evaluation following an abnormal mammogram or newly diagnosed with breast cancer completed questionnaires and provided blood samples to assess EBV viral capsid antigen (VCA) IgG antibody titers. Results: More highly educated women with more support from friends had lower EBV VCA antibody titers, reflecting a stronger cellular immune response to the latent virus; however, among less educated women, friend support was not associated with EBV antibody titers. As revealed in an ancillary analysis, more highly educated women with more friend support had lower systolic blood pressure (SBP); however, friend support was not associated with SBP among less educated women. Neither depression nor perceived stress mediated these associations. Neither cancer status nor cancer stage among those diagnosed with cancer was significantly related to these outcomes. Conclusion: Lower SES women may not reap the same immunological benefits from friend support when experiencing a stressful life event as their higher SES counterparts.
C1 [Fagundes, Christopher P.] Ohio State Univ, Coll Med, Inst Behav Med Res, Columbus, OH 43210 USA.
[Bennett, Jeanette M.] Ohio State Univ, Coll Dent, Columbus, OH 43210 USA.
[Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA.
RP Fagundes, CP (reprint author), Ohio State Univ, Coll Med, Inst Behav Med Res, 460 Med Ctr Dr, Columbus, OH 43210 USA.
EM christopher.fagundes@osumc.edu
RI Kiecolt-Glaser, Janice/A-3236-2009; Agnese, Doreen/I-1351-2012; Povoski,
Stephen/E-3887-2011; Carson, William/E-2846-2011; Glaser,
Ronald/E-3124-2011;
OI Kiecolt-Glaser, Janice/0000-0003-4900-9578; Bennett, Jeanette
M./0000-0002-8487-9774
FU NIH [CA131029, CA126857, DE014320, UL1RR025755, CA016058]; American
Cancer Society [PF-11-007-01-CPPB]
FX Work on this project was supported by NIH grants CA131029, CA126857,
DE014320, UL1RR025755, and CA016058, and a Postdoctoral Fellowship Grant
from the American Cancer Society awarded to the first author
PF-11-007-01-CPPB. We appreciate the helpful assistance of Arenda Nolan,
Mary Lower, and Cathie Atkinson.
NR 58
TC 14
Z9 14
U1 2
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD JAN
PY 2012
VL 31
IS 1
BP 11
EP 19
DI 10.1037/a0025599
PG 9
WC Psychology, Clinical; Psychology
SC Psychology
GA 878MM
UT WOS:000299261200003
PM 22004465
ER
PT J
AU Dillard, AJ
Ferrer, RA
Ubel, PA
Fagerlin, A
AF Dillard, Amanda J.
Ferrer, Rebecca A.
Ubel, Peter A.
Fagerlin, Angela
TI Risk Perception Measures' Associations With Behavior Intentions, Affect,
and Cognition Following Colon Cancer Screening Messages
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE feelings-of-risk; comparative risk perceptions; absolute risk
perceptions; behavioral intentions; cancer screening
ID BREAST-CANCER; COLORECTAL-CANCER; WOMENS PERCEPTIONS; ATTITUDE-CHANGE;
COMMUNICATION; ABSOLUTE; SUSCEPTIBILITY; PARTICIPATION; INFORMATION;
MAMMOGRAPHY
AB Objective: Risk perception is important for motivating health behavior (e. g., Janz & Becker, 1984), but different measures of the construct may change how important that relationship appears. In two studies, we examined associations between four measures of risk perception, health behavior intentions and possible behavioral determinants. Methods: Participants in these studies, who were due for colorectal cancer screening, read an online message about the importance of screening to reduce the chance of cancer. We examined bivariate and multivariate associations between risk perception measures, including absolute, comparative, and feelings-of-risk, and behavioral intentions to screen, general worry, and knowledge and attitudes related to screening. Results: Results across the two studies were consistent, with all risk perception measures being correlated with intentions and attitudes. Multivariate analyses revealed that feelings-of-risk was most predictive of all variables, with the exception of general worry, for which comparative measures were the most predictive. Conclusions: Researchers interested in risk perception should assess feelings-of-risk along with more traditional measures. Those interested in influencing health behavior specifically should attempt to increase feelings of vulnerability rather than numerical risk.
C1 [Dillard, Amanda J.] Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA.
[Ferrer, Rebecca A.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 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.
[Fagerlin, Angela] Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA.
[Fagerlin, Angela] VA Hlth Care Syst, Ann Arbor, MI USA.
RP Dillard, AJ (reprint author), Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA.
EM dillaram@gvsu.edu
FU Foundation for Informed Medical Decision Making
FX These studies were funded by a George Bennett Postdoctoral grant from
the Foundation for Informed Medical Decision Making. We thank Bill Klein
for comments on a draft of the manuscript.
NR 46
TC 38
Z9 38
U1 8
U2 35
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
EI 1930-7810
J9 HEALTH PSYCHOL
JI Health Psychol.
PD JAN
PY 2012
VL 31
IS 1
BP 106
EP 113
DI 10.1037/a0024787
PG 8
WC Psychology, Clinical; Psychology
SC Psychology
GA 878MM
UT WOS:000299261200015
PM 21806302
ER
PT J
AU Edlich, B
Ahlenstiel, G
Azpiroz, AZ
Stoltzfus, J
Noureddin, M
Serti, E
Feld, JJ
Liang, TJ
Rotman, Y
Rehermann, B
AF Edlich, Birgit
Ahlenstiel, Golo
Azpiroz, Aintzane Zabaleta
Stoltzfus, Jonathan
Noureddin, Mazen
Serti, Elisavet
Feld, Jordan J.
Liang, T. Jake
Rotman, Yaron
Rehermann, Barbara
TI Early changes in interferon signaling define natural killer cell
response and refractoriness to interferon-based therapy of hepatitis C
patients
SO HEPATOLOGY
LA English
DT Article
ID VIROLOGICAL RESPONSE; VIRUS; RIBAVIRIN; PEGINTERFERON; EXPRESSION;
INFECTION; GAMMA; STAT1; HCV
AB Natural killer (NK) cells exhibit a polarized phenotype with increased cytotoxicity and decreased interferon gamma (IFN-?) production in chronic hepatitis C virus (HCV) infection. Here, we asked whether this is caused by type I interferon (IFN)-induced expression and phosphorylation levels of signal transducer and activator of transcription (STAT) molecules in NK cells and whether it affects the response and refractoriness of NK cells to IFN-a-based therapy of HCV. STAT1 levels in NK cells were significantly higher in patients with chronic HCV infection than in uninfected controls. STAT1 levels and induction of phosphorylated STAT1 (pSTAT1) increased further during IFN-a-based therapy with preferential STAT1 over STAT4 phosphorylation. Induction of pSTAT1 correlated with increased NK cytotoxicity (tumor necrosis factorapoptosis-inducing ligand [TRAIL] expression and degranulation) and decreased IFN-? production. NK cells from patients with a greater than 2 log10 first-phase HCV RNA decline to IFN-a-based therapy (>99% IFN effectiveness) displayed strong pSTAT1 induction in vivo and were refractory to further stimulation in vitro. In contrast, NK cells from patients with a less than 2 log10 first-phase HCV RNA decline exhibited lower pSTAT1 induction in vivo (P = 0.024), but retained greater IFN-a responsiveness in vitro (P = 0.024). NK cells of all patients became refractory to in vivo and in vitro stimulation by IFN-a during the second-phase virological response. Conclusion: These data show that IFN-a-induced modulation of STAT1/4 phosphorylation underlies the polarization of NK cells toward increased cytotoxicity and decreased IFN-? production in HCV infection, and that NK cell responsiveness and refractoriness correlate to the antiviral effectiveness of IFN-a-based therapy. (Hepatology 2012;55:39-48)
C1 [Edlich, Birgit; Ahlenstiel, Golo; Azpiroz, Aintzane Zabaleta; Stoltzfus, Jonathan; Noureddin, Mazen; Serti, Elisavet; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM Rehermann@nih.gov
RI Zabaleta, Aintzane/K-8936-2014;
OI Rotman, Yaron/0000-0002-7549-8216; Ahlenstiel, Golo/0000-0003-0026-1457
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health intramural
research program.
NR 23
TC 56
Z9 58
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2012
VL 55
IS 1
BP 39
EP 48
DI 10.1002/hep.24628
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 867WS
UT WOS:000298486100007
PM 21898483
ER
PT J
AU Lau, JYF
Guyer, AE
Tone, EB
Jenness, J
Parrish, JM
Pine, DS
Nelson, EE
AF Lau, Jennifer Y. F.
Guyer, Amanda E.
Tone, Erin B.
Jenness, Jessica
Parrish, Jessica M.
Pine, Daniel S.
Nelson, Eric E.
TI Neural responses to peer rejection in anxious adolescents: Contributions
from the amygdala-hippocampal complex
SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT
LA English
DT Article; Proceedings Paper
CT 2nd Herzliyah Symposium on Developmental Psychopathology
CY JUN 07-10, 2010
CL Sch Psychol, Herzliya, ISRAEL
HO Sch Psychol
DE adolescence; amygdala; anxiety; peer rejection
ID GENERALIZED ANXIETY DISORDER; SOCIAL ANXIETY; PREFRONTAL CORTEX;
EMOTIONAL INFORMATION; ANTERIOR CINGULATE; ATTENTIONAL BIAS; CHILDREN;
DEPRESSION; COMMON; WORLD
AB Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender- and IQ-matched, psychiatrically healthy adolescents received "not interested" and "interested" feedback from unknown peers during a chat room task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high-desirability ratings. Further highlighting the salience of such feedback, all adolescents, independently of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety.
C1 [Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Guyer, Amanda E.] Univ Calif, Davis, CA USA.
[Tone, Erin B.] Georgia State Univ, Atlanta, GA 30303 USA.
[Jenness, Jessica] Univ Denver, Denver, CO 80208 USA.
[Parrish, Jessica M.] Catholic Univ, Washington, DC USA.
[Pine, Daniel S.; Nelson, Eric E.] NIH, Bethesda, MD USA.
RP Lau, JYF (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
EM jennifer.lau@psy.ox.ac.uk
OI Nelson, Eric/0000-0002-3376-2453
NR 44
TC 19
Z9 19
U1 5
U2 23
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0165-0254
J9 INT J BEHAV DEV
JI Int. J. Behav. Dev.
PD JAN
PY 2012
VL 36
IS 1
BP 36
EP 44
DI 10.1177/0165025411406854
PG 9
WC Psychology, Developmental
SC Psychology
GA 863SP
UT WOS:000298188500006
ER
PT J
AU Patel, K
Dixit, VD
Lee, JH
Kim, JW
Schaffer, EM
Nguyen, D
Taub, DD
AF Patel, Kalpesh
Dixit, Vishwa Deep
Lee, Jun Ho
Kim, Jie Wan
Schaffer, Eric M.
Nguyen, Dzung
Taub, Dennis D.
TI The GHS-R Blocker D-[Lys3] GHRP-6 Serves as CCR5 Chemokine Receptor
Antagonist
SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
LA English
DT Article
DE MIP-1 alpha; MIP-1 beta; RANTES; CCR5; HIV-1; Ghrelin; GHRP-6; GHS-R1a;
Inflammation; Cancer
ID HIV ENTRY INHIBITORS; SMALL-MOLECULE; GHRELIN; GROWTH; PROGRESS
AB [D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. This antagonist is one of the most common antagonists utilized in vivo to block GHS-R function and activity. Here, we found that DLS also has the ability to modestly block chemokine function and ligand binding to the chemokine receptor CCR5. The DLS effects on RANTES binding and Erk signaling as well as calcium mobilization appears to be much stronger than its effects on MIP-1 alpha and MIP-1 beta. CCR5 have been shown to act as major co-receptor for HIV-1 entry into the CD4 positive host cells. To this end, we also found that DLS blocks M-tropic HIV-1 propagation in activated human PBMCs. These data demonstrate that DLS may not be a highly selective GHS-R1a inhibitor and may also effects on other G-protein coupled receptor (GPCR) family members. Moreover, DLS may have some potential clinical applications in blocking HIV infectivity and CCR5-mediated migration and function in various inflammatory disease states.
C1 [Patel, Kalpesh; Dixit, Vishwa Deep; Lee, Jun Ho; Kim, Jie Wan; Schaffer, Eric M.; Nguyen, Dzung; Taub, Dennis D.] NIA, Lab Mol Biol & Immunol, Intramural Program, NIH, Baltimore, MD 21224 USA.
RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Lab Mol Biol & Immunol, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Taubd@grc.nia.nih.gov
RI Patel, Kalpesh/G-6685-2012
OI Patel, Kalpesh/0000-0002-2952-6773
FU National Institute on Aging, National Institutes of Health
FX We would like to thank Mr. Gary Collins for his assistance in the
completion of this work. This work was supported by the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health.
NR 16
TC 11
Z9 11
U1 0
U2 2
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1449-1907
J9 INT J MED SCI
JI Int. J. Med. Sci.
PY 2012
VL 9
IS 1
BP 51
EP 58
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 861IR
UT WOS:000298013100009
PM 22211090
ER
PT J
AU Simone, CB
Kramer, K
O'Meara, WP
Bekelman, JE
Belard, A
McDonough, J
O'Connell, J
AF Simone, Charles B., II
Kramer, Kevin
O'Meara, William P.
Bekelman, Justin E.
Belard, Arnaud
McDonough, James
O'Connell, John
TI PREDICTED RATES OF SECONDARY MALIGNANCIES FROM PROTON VERSUS PHOTON
RADIATION THERAPY FOR STAGE I SEMINOMA
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Seminoma; Secondary malignancies; Proton therapy; Dosimetry; Para-aortic
ID TESTICULAR-CANCER; RANDOMIZED-TRIAL; 2ND CANCERS; ADJUVANT TREATMENT;
TESTIS CANCER; RADIOTHERAPY; RISK; SURVEILLANCE; MORTALITY; SURVIVORS
AB Purpose: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities.
Methods and Material: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors.
Results: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06).
Conclusions: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity. (C) 2012 Elsevier Inc.
C1 [Simone, Charles B., II] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Simone, Charles B., II; Bekelman, Justin E.; McDonough, James] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Kramer, Kevin; Belard, Arnaud] Henry M Jackson Fdn Advancement Mil Med, Rockville, MD USA.
[O'Meara, William P.] Natl Naval Med Ctr, Div Radiat Oncol, Bethesda, MD USA.
[O'Connell, John] Walter Reed Army Med Ctr, Radiat Oncol Serv, Washington, DC 20307 USA.
RP Simone, CB (reprint author), NCI, NIH, Radiat Oncol Branch, Bldg 10 CRC,Room B2-3500,10 Ctr Dr, Bethesda, MD 20892 USA.
EM csimone@alumni.upenn.edu
FU U.S. Army Medical Research and Materiel Command
[DAMD17-W81XWH-04-2-0022]
FX This work was supported by U.S. Army Medical Research and Materiel
Command under Contract Agreement No. DAMD17-W81XWH-04-2-0022. Views
expressed in the manuscript are those of the authors and do not reflect
official policies of the U.S. Government or Department of Army, Navy, or
Defense.
NR 33
TC 17
Z9 17
U1 0
U2 6
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 JAN
PY 2012
VL 82
IS 1
BP 242
EP 249
DI 10.1016/j.ijrobp.2010.11.021
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 868LZ
UT WOS:000298526100036
PM 21236595
ER
PT J
AU Viswanathan, AN
Creutzberg, CL
Craighead, P
McCormack, M
Toita, T
Narayan, K
Reed, N
Long, H
Kim, HJ
Marth, C
Lindegaard, JC
Cerrotta, A
Small, W
Trimble, E
AF Viswanathan, Akila N.
Creutzberg, Carien L.
Craighead, Peter
McCormack, Mary
Toita, Takafumi
Narayan, Kailash
Reed, Nicholas
Long, Harry
Kim, Hak-Jae
Marth, Christian
Lindegaard, Jacob C.
Cerrotta, Annmarie
Small, William, Jr.
Trimble, Edward
TI INTERNATIONAL BRACHYTHERAPY PRACTICE PATTERNS: A SURVEY OF THE
GYNECOLOGIC CANCER INTERGROUP (GCIG)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Brachytherapy; Cervical cancer; Radiation dose
ID HIGH-DOSE-RATE; CERVICAL-CANCER; INTRACAVITARY BRACHYTHERAPY;
FRACTIONATION SCHEDULE; RADIOTHERAPY; RECOMMENDATIONS; CARCINOMA; TRIAL
AB Purpose: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm).
Methods and Materials: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey.
Results: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4:96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05;p = 0.02 for Asia vs. other regions). The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002).
Conclusion: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials. (C) 2012 Elsevier Inc.
C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Creutzberg, Carien L.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands.
[Craighead, Peter] Tom Baker Canc Clin, Calgary, AB, Canada.
[McCormack, Mary] Univ Coll London Hosp, Dept Oncol, London, England.
[Toita, Takafumi] Univ Ryukyus, Grad Sch Med Sci, Dept Radiol, Okinawa, Japan.
[Narayan, Kailash] Univ Melbourne, Peter MacCallum Canc Ctr, Div Radiat Oncol, Melbourne, Vic, Australia.
[Narayan, Kailash] Univ Melbourne, Dept Obstet & Gynecol, Melbourne, Vic, Australia.
[Reed, Nicholas] Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland.
[Long, Harry] Mayo Clin, Coll Med, Dept Oncol, Div Med Oncol, Rochester, MN USA.
[Kim, Hak-Jae] Seoul Natl Univ Hosp, Dept Oncol, Seoul 110744, South Korea.
[Marth, Christian] Med Univ Innsbruck, Innsbruck, Austria.
[Lindegaard, Jacob C.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
[Cerrotta, Annmarie] Fdn IRCCS Ist Nazl Tumori, Dept Radiat Therapy, Milan, Italy.
[Small, William, Jr.] Robert H Lurie Comprehens Canc NW Univ, Chicago, IL USA.
[Trimble, Edward] NCI, Bethesda, MD 20892 USA.
RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA.
EM aviswanathan@lroc.harvard.edu
RI Cerrotta, Annamaria/D-8063-2017;
OI Cerrotta, Annamaria/0000-0001-7926-3716; Viswanathan,
Akila/0000-0002-2003-0392
FU NCI NIH HHS [K07 CA117979]
NR 20
TC 59
Z9 60
U1 2
U2 9
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 JAN
PY 2012
VL 82
IS 1
BP 250
EP 255
DI 10.1016/j.ijrobp.2010.10.030
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 868LZ
UT WOS:000298526100037
PM 21183288
ER
PT J
AU Shomaker, LB
Tanofsky-Kraff, M
Zocca, JM
Field, SE
Drinkard, B
Yanovski, JA
AF Shomaker, Lauren B.
Tanofsky-Kraff, Marian
Zocca, Jaclyn M.
Field, Sara E.
Drinkard, Bart
Yanovski, Jack A.
TI Depressive Symptoms and Cardiorespiratory Fitness in Obese Adolescents
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
ID PHYSICAL-ACTIVITY; CHILDREN; CHILDHOOD; METAANALYSIS; EXERCISE; YOUNG;
PREVALENCE; OVERWEIGHT; AMERICAN; VALIDITY
AB Purpose: Depressive symptoms in adolescents have been associated with reduced physical activity. However, existing studies have relied on questionnaire measures of physical activity, which may not necessarily reflect actual energy expenditures. We sought to evaluate the relationship between depressive symptoms and objectively measured cardiorespiratory fitness among severely obese adolescents.
Methods: One hundred thirty-four obese (body mass index [kg/m(2)]: >= 95th percentile) adolescent girls and boys (ages: 12-17 years) reported their depressive symptoms on the Children's Depression Inventory. Adolescents also participated in a maximal cycle ergometry exercise test to measure cardiorespiratory fitness. Body composition was assessed with dual-energy X-ray absorptiometry scanning.
Results: Among the 103 adolescents who reached maximal exertion, those with elevated depressive symptoms (16%) displayed poorer cardiorespiratory fitness than those without elevated depressive symptoms (maximal oxygen uptake: 1,873.2 +/- 63.6 vs. 2,012.9 +/- 28.6 mL/min, p < .05). Symptoms of anhedonia also were related to lower fitness levels (p < .05). These effects were observed after accounting for age, sex, race, and lean mass.
Conclusions: Among obese adolescents, elevated depressive symptoms are associated with poorer objectively measured cardiorespiratory fitness. Future experimental tests should investigate whether cardiorespiratory fitness acts as a mediator of adolescent depressive symptoms' effect on obesity or obesity-related health comorbidities. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Field, Sara E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Drinkard, Bart] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD [1F32HD056762, 1ZIAHD000641]; NIMHD; OBSSR
FX The present study was supported by National Research Service Award
1F32HD056762 from the NICHD (to L.S.), and Intramural Research Program
grant 1ZIAHD000641 from the NICHD with supplemental funding from NIMHD
and OBSSR (to J.Y.).
NR 40
TC 12
Z9 14
U1 0
U2 12
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 JAN
PY 2012
VL 50
IS 1
BP 87
EP 92
DI 10.1016/j.jadohealth.2011.05.015
PG 6
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 866HH
UT WOS:000298370700013
PM 22188839
ER
PT J
AU Rao, JS
Kellom, M
Reese, EA
Rapoport, SI
Kim, HW
AF Rao, Jagadeesh Sridhara
Kellom, Matthew
Reese, Edmund Arthur
Rapoport, Stanley Isaac
Kim, Hyung-Wook
TI Dysregulated glutamate and dopamine transporters in postmortem frontal
cortex from bipolar and schizophrenic patients
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar disorder; Glutamate transporter; Dopamine reuptake transporter;
Schizophrenia; Serotonin transporter
ID DORSOLATERAL PREFRONTAL CORTEX; ARACHIDONIC-ACID; NMDA RECEPTOR;
SEROTONIN TRANSPORTER; NEURODEGENERATIVE DISEASES; TRANSCRIPTION FACTOR;
UNANESTHETIZED RATS; AFFECTIVE-DISORDER; ELDERLY-PATIENTS;
GENE-EXPRESSION
AB Background: Dysregulated glutamate, serotonin and dopamine neurotransmission has been reported in bipolar disorder (BD) and schizophrenia (SZ), but the underlying mechanisms of dysregulation are not clear. We hypothesized that they involve alterations in excitatory amino acid transporters (EAATs), the serotonin reuptake transporter (SERT), and the dopamine reuptake transporter (DAT).
Methods: To test this hypothesis, we determined protein and mRNA levels of EMT subtypes 1-4, of the SERT and of the DAT in postmortem frontal cortex from BD (n = 10) and SZ (n = 10) patients and from healthy control (n = 10) subjects.
Results: Compared to control levels, protein and mRNA levels of EAAT1 were increased significantly in cortex from both BD and SZ patients. EAAT2 protein and mRNA levels were decreased significantly in BD but not in SZ cortices. EAAT3 and EAAT 4 protein and mRNA levels were significantly higher in SZ but not in BD compared with control. DAT protein and mRNA levels were decreased significantly in both BD and SZ cortices. There was no significant change in SERT expression in either BD or SZ.
Conclusions: The altered EAATs and DAT expression could result in altered glutamatergic and hyperdopaminergic function in BD and SZ. Differently altered EAATs involved in glutamatergic transmission could be therapeutic targets for treating BD and SZ. Published by Elsevier B.V.
C1 [Rao, Jagadeesh Sridhara; Kellom, Matthew; Reese, Edmund Arthur; Rapoport, Stanley Isaac; Kim, Hyung-Wook] NIA, BPMS, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, BPMS, NIH, 9000 Rockville Pike,Bldg 9,Rm 1S-126, Bethesda, MD 20892 USA.
EM jrao@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health, Bethesda [MD
20892]; PHS [R24MH068855]
FX This research was entirely supported by the Intramural Research Programs
of the National Institute on Aging, National Institutes of Health,
Bethesda, MD 20892.; We thank the Harvard Brain Bank, Boston, MA for
providing the postmortem brain samples under PHS grant number
R24MH068855.
NR 71
TC 58
Z9 59
U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JAN
PY 2012
VL 136
IS 1-2
BP 63
EP 71
DI 10.1016/j.jad.2011.08.017
PG 9
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 867JW
UT WOS:000298451700008
PM 21925739
ER
PT J
AU Whitehead, GS
Wilson, RH
Nakano, K
Burch, LH
Nakano, H
Cook, DN
AF Whitehead, Gregory S.
Wilson, Rhonda H.
Nakano, Keiko
Burch, Lauranell H.
Nakano, Hideki
Cook, Donald N.
TI IL-35 production by inducible costimulator (ICOS)-positive regulatory T
cells reverses established IL-17-dependent allergic airways disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; airway hyperresponsiveness; airway hyperresponsiveness; IL-17;
T(H)17; T(H)2; IL-35; inducible costimulator; ovalbumin
ID TH17 CELLS; T(H)17 CELLS; ASTHMA; INFLAMMATION; IL-17;
HYPERRESPONSIVENESS; INTERLEUKIN-17; RESPONSES; MICE; CD4
AB Background: Recent evidence suggests that IL-17 contributes to airway hyperresponsiveness (AHR); however, the mechanisms that suppress the production of this cytokine remain poorly defined.
Objective: We sought to identify the regulatory cells and molecules that suppress IL-17-dependent allergic airways disease.
Methods: Mice were sensitized by means of airway instillations of ovalbumin together with low levels of LPS. Leukocyte recruitment to the lung and AHR were assessed after daily challenges with aerosolized ovalbumin. Flow cytometry, quantitative PCR, and gene-targeted mice were used to identify naturally arising subsets of regulatory T (Treg) cells and their cytokines required for the suppression of established allergic airway disease.
Results: Allergic sensitization through the airway primed both effector and regulatory responses. Effector responses were initially dominant and led to airway inflammation and IL-17-dependent AHR. However, after multiple daily allergen challenges, IL-17 production and AHR decreased, even though pulmonary levels of T(H)17 cells remained