FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Shockley, KR
AF Shockley, Keith R.
TI A Three-Stage Algorithm to Make Toxicologically Relevant Activity Calls
from Quantitative High Throughput Screening Data
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE activity calls; concentration-response; Hill equation; quantitative high
throughput screening; Tox21
ID TOXICITY
AB BACKGROUND: The ability of a substance to induce a toxicological response is better understood by analyzing the response profile over a broad range of concentrations than at a single concentration. In vitro quantitative high throughput screening (qHTS) assays are multiple-concentration experiments with an important role in the National Toxicology Program's (NTP) efforts to advance toxicology from a predominantly observational science at the level of disease-specific models to a more predictive science based on broad inclusion of biological observations.
OBJECTIVE: We developed a systematic approach to classify substances from large-scale concentration response data into statistically supported, toxicologically relevant activity categories.
METHODS: The first stage of the approach finds active substances with robust concentration response profiles within the tested concentration range. The second stage finds substances with activity at the lowest tested concentration not captured in the first stage. The third and final stage separates statistically significant (but not robustly statistically significant) profiles from responses that lack statistically compelling support (i.e., "inactives"). The performance of the proposed algorithm was evaluated with simulated qHTS data sets.
RESULTS: The proposed approach performed well for 14-point-concentration response curves with typical levels of residual error (sigma <= 25%) or when maximal response (vertical bar RMAX vertical bar) was > 25% of the positive control response. The approach also worked well in most cases for smaller sample sizes when vertical bar RMAX vertical bar >= 50%, even with as few as four data points.
CONCLUSIONS: The three-stage classification algorithm performed better than one-stage classification approaches based on overall F-tests, t-tests, or linear regression.
C1 NIEHS, Biostat Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Shockley, KR (reprint author), NIEHS, Biostat Branch, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shockleykr@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health, NIEHS
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, NIEHS.
NR 22
TC 6
Z9 6
U1 0
U2 9
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2012
VL 120
IS 8
BP 1107
EP 1115
DI 10.1289/ehp.1104688
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 985JN
UT WOS:000307260500021
PM 22575717
ER
PT J
AU Shukla, SJ
Huang, RL
Simmons, SO
Tice, RR
Witt, KL
VanLeer, D
Ramabhadran, R
Austin, CP
Xia, MH
AF Shukla, Sunita J.
Huang, Ruili
Simmons, Steven O.
Tice, Raymond R.
Witt, Kristine L.
VanLeer, Danielle
Ramabhadran, Ram
Austin, Christopher P.
Xia, Menghang
TI Profiling Environmental Chemicals for Activity in the Antioxidant
Response Element Signaling Pathway Using a High Throughput Screening
Approach
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE ARE; Nrf2; oxidative stress; qHTS; toxicity; Tox21
ID DNA-DAMAGE; IN-VITRO; BIOLOGICAL EVALUATION; TRANSCRIPTION FACTORS;
MEDIATED EXPRESSION; OXIDATIVE STRESS; GENE; NRF2; ACTIVATION; INDUCTION
AB BACKGROUND: Oxidative stress has been implicated in the pathogenesis of a variety of diseases ranging from cancer to neurodegeneration, highlighting the need to identify chemicals that can induce this effect. The antioxidant response element (ARE) signaling pathway plays an important role in the amelioration of oxidative stress. Thus, assays that detect the up-regulation of this pathway could be useful for identifying chemicals that induce oxidative stress.
OBJECTIVES: We used cell-based reporter methods and informatics tools to efficiently screen a large collection of environmental chemicals and identify compounds that induce oxidative stress.
METHODS: We utilized two cell-based ARE assay reporters, beta-lactamase and luciferase, to screen a U.S. National Toxicology Program 1,408-compound library (NTP 1408, which contains 1,340 unique compounds) for their ability to induce oxidative stress in HepG2 cells using quantitative high throughput screening (qHTS).
RESULTS: Roughly 3% (34 of 1,340) of the unique compounds demonstrated activity across both cell-based assays. Based on biological activity and structure activity relationship profiles, we selected 50 compounds for retesting in the two ARE assays and in an additional follow-up assay that employed a mutated ARE linked to beta-lactamase. Using this strategy, we identified 30 compounds that demonstrated activity in the ARE-bla and ARE-Inc assays and were able to determine structural features conferring compound activity across assays.
CONCLUSIONS: Our results support the robustness of using two different cell-based approaches for identifying compounds that induce ARE signaling. Together, these methods are useful for prioritizing chemicals for further in-depth mechanism-based toxicity testing.
C1 [Shukla, Sunita J.; Huang, Ruili; VanLeer, Danielle; Austin, Christopher P.; Xia, Menghang] NIH, NIH Chem Genom Ctr, US Dept HHS, Rockville, MD USA.
[Simmons, Steven O.; Ramabhadran, Ram] US EPA, Res Triangle Pk, NC 27711 USA.
[Tice, Raymond R.; Witt, Kristine L.] NIEHS, Div Natl Toxicol Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Xia, MH (reprint author), NIH, NIH Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov
OI Simmons, Steven/0000-0001-9079-1069
FU National Institute of Environmental Health Sciences, National Institutes
of Health; U.S. Environmental Protection Agency (EPA)
FX This work was supported by the Intramural Research Programs of the
National Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, as well as the U.S.
Environmental Protection Agency (EPA).
NR 46
TC 12
Z9 12
U1 4
U2 25
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2012
VL 120
IS 8
BP 1150
EP 1156
DI 10.1289/ehp.1104709
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 985JN
UT WOS:000307260500027
PM 22551509
ER
PT J
AU Birnbaum, LS
AF Birnbaum, Linda S.
TI NIEHS's New Strategic Plan
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Birnbaum, Linda S.] NIEHS, Chem Disposit Group, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, Chem Disposit Group, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov
NR 1
TC 6
Z9 6
U1 0
U2 1
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2012
VL 120
IS 8
BP A298
EP A298
DI 10.1289/ehp.1205642
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 985JN
UT WOS:000307260500001
PM 22853936
ER
PT J
AU Vermeulen, R
Attfield, M
Stewart, PA
Coble, JB
Blair, A
Lubin, JH
Silverman, DT
AF Vermeulen, Roel
Attfield, Michael
Stewart, Patricia A.
Coble, Joseph B.
Blair, Aaron
Lubin, Jay H.
Silverman, Debra T.
TI A Retrospective Assessment of Occupational Exposure to Elemental Carbon
in the U.S. Trucking Industry
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
ID NONMETAL MINING FACILITIES; DIESEL EXHAUST; MINERS
C1 [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Attfield, Michael] NIOSH, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA.
[Stewart, Patricia A.; Coble, Joseph B.; Blair, Aaron; Lubin, Jay H.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
EM silvermd@mail.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 10
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2012
VL 120
IS 8
BP A302
EP A302
DI 10.1289/ehp.1104253
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 985JN
UT WOS:000307260500003
ER
PT J
AU Kuzin, A
Kundu, M
Ross, J
Koizumi, K
Brody, T
Odenwald, WF
AF Kuzin, Alexander
Kundu, Mukta
Ross, Jermaine
Koizumi, Keita
Brody, Thomas
Odenwald, Ward F.
TI The cis-regulatory dynamics of the Drosophila CNS determinant castor are
controlled by multiple sub-pattern enhancers
SO GENE EXPRESSION PATTERNS
LA English
DT Article
DE Drosophila CNS development; cis-Regulatory DNA; Sub-pattern enhancers;
DNA sequence conservation; Castor gene regulation
ID DEVELOPING NERVOUS-SYSTEM; EXPRESSION; BRAIN; SPECIFICATION; GENE;
IDENTIFICATION; DATABASE; NEURONS; DNA; CONSERVATION
AB In the developing CNS, unique functional identities among neurons and glia are, in part, established as a result of successive transitions in gene expression programs within neural precursor cells. One of the temporal-identity windows within Drosophila CNS neural precursor cells or neuroblasts (NBs) is marked by the expression of a zinc-finger transcription factor (TF) gene, castor (ass). Our analysis of cis-regulatory DNA within a cas loss-of-function rescue fragment has identified seven enhancers that independently activate reporter transgene expression in specific sub-patterns of the wild-type embryonic cas gene expression domain. Most of these enhancers also regulate different aspects of cas expression within the larval and adult CNS. Phylogenetic footprinting reveals that each enhancer is made up of clusters of highly conserved DNA sequence blocks that are flanked by less-conserved inter-cluster spacer sequences. Comparative analysis of the conserved DNA also reveals that cos enhancers share different combinations of sequence elements and many of these shared elements contain core DNA-binding recognition motifs for characterized temporal-identity TFs. Intra-species alignments show that two of the sub-pattern enhancers originated from an inverted duplication and that this repeat is unique to the cas locus in all sequenced Drosophila species. Finally we show that three of the enhancers differentially require cas function for their wild-type regulatory behavior. Cas limits the expression of one enhancer while two others require cas function for full expression. These studies represent a starting point for the further analysis of cas gene expression and the TFs that regulate it. Published by Elsevier B.V.
C1 [Kuzin, Alexander; Kundu, Mukta; Ross, Jermaine; Koizumi, Keita; Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
RP Kuzin, A (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kuzina@ninds.nih.gov; brodyt@ninds.nih.gov; odenwaldw@ninds.nih.gov
FU Intramural Research Program of the NIH, NINDS
FX The authors would like to thank Takeshi Awasaki for his comments,
Antonios Ekatomatis for technical assistance and Judith Brody for
editorial expertise. This research was supported by the Intramural
Research Program of the NIH, NINDS.
NR 40
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-133X
J9 GENE EXPR PATTERNS
JI Gene Expr. Patterns
PD AUG-SEP
PY 2012
VL 12
IS 7-8
BP 261
EP 272
DI 10.1016/j.gep.2012.05.004
PG 12
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 014JP
UT WOS:000309372200006
PM 22691242
ER
PT J
AU Jobe, JB
Adams, AK
Henderson, JA
Karanja, N
Lee, ET
Walters, KL
AF Jobe, Jared B.
Adams, Alexandra K.
Henderson, Jeffrey A.
Karanja, Njeri
Lee, Elisa T.
Walters, Karina L.
TI Community-Responsive Interventions to Reduce Cardiovascular Risk in
American Indians
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Review
DE Behavioral risk for cardiovascular disease; Diabetes; Lifestyle changes
ID ALASKA-NATIVE POPULATIONS; THRIFTY GENOTYPE; UNITED-STATES; EPIDEMIC;
PROGRAM; DISEASE
AB American Indian and Alaska Native (AI/AN) populations bear a heavy burden of cardiovascular disease (CVD), and they have the highest rates of risk factors for CVD, such as cigarette smoking, obesity, and diabetes, of any U.S. population group. Yet, few randomized controlled trials have been launched to test potential preventive interventions in Indian Country. Five randomized controlled trials were initiated recently in AI/AN communities to test the effectiveness of interventions targeting adults and/or children to promote healthy behaviors that are known to impact biological CVD risk factors. This article provides a context for and an overview of these five trials. The high burden of CVD among AI/AN populations will worsen unless behaviors and lifestyles affecting CVD risk can be modified. These five trials, if successful, represent a starting point in addressing these significant health disparities.
C1 [Jobe, Jared B.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Adams, Alexandra K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA.
[Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA.
[Karanja, Njeri] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA.
[Walters, Karina L.] Univ Washington, Indigenous Wellness Res Inst, Seattle, WA 98195 USA.
[Walters, Karina L.] Univ Washington, Sch Social Work, Seattle, WA 98195 USA.
RP Jobe, JB (reprint author), NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
EM jobej@mail.nih.gov
FU NHLBI NIH HHS [U01 HL087422]
NR 26
TC 3
Z9 3
U1 2
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 153
EP 159
DI 10.1007/s10935-012-0277-9
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100001
PM 22983753
ER
PT J
AU Karanja, N
Aickin, M
Lutz, T
Mist, S
Jobe, J
Maupome, G
Ritenbaugh, C
AF Karanja, Njeri
Aickin, Mikel
Lutz, Tam
Mist, Scott
Jobe, Jared B.
Maupome, Gerardo
Ritenbaugh, Cheryl
TI A Community-Based Intervention to Prevent Obesity Beginning at Birth
Among American Indian Children: Study Design and Rationale for the PTOTS
Study
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE Primary obesity prevention; Infants; Toddlers; American Indians
ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; HEALTH PROMOTION;
PRESCHOOL-CHILDREN; ADOLESCENT OBESITY; CHILDHOOD OBESITY; SOCIAL
ECOLOGY; FEEDING STYLE; RISK-FACTORS; AGED 6
AB Eating and physical activity behaviors associated with adult obesity have early antecedents, yet few studies have focused on obesity prevention interventions targeting very young children. Efforts to prevent obesity beginning at birth seem particularly important in populations at risk for early-onset obesity. National estimates indicate that American Indian (AI) children have higher rates of overweight and obesity than children of other races/ethnicities. The Prevention of Toddler Obesity and Teeth Health Study (PTOTS) is a community-partnered randomized controlled trial designed to prevent obesity beginning at birth in AI children. PTOTS was developed to test the effectiveness of a multi-component intervention designed to: promote breastfeeding, reduce sugar-sweetened beverage consumption, appropriately time the introduction of healthy solid foods, and counsel parents to reduce sedentary lifestyles in their children. A birth cohort of 577 children from five AI tribes is randomized by tribe to either the intervention (three tribes) or the comparison condition (two tribes). The strengths and weaknesses of PTOTS include a focus on a critical growth phase, placement in the community, and intervention at many levels, using a variety of approaches.
C1 [Karanja, Njeri] Kaiser Permanente NW Hawaii SE, Ctr Hlth Res, Portland, OR 97227 USA.
[Aickin, Mikel; Ritenbaugh, Cheryl] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA.
[Lutz, Tam; Mist, Scott] NW Portland Area Indian Hlth Board, Portland, OR USA.
[Jobe, Jared B.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Maupome, Gerardo] Indiana Univ, Sch Dent, Dept Prevent & Community Dent, Regenstrief Inst Inc, Indianapolis, IN USA.
[Jobe, Jared B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Karanja, N (reprint author), Kaiser Permanente NW Hawaii SE, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA.
EM Njeri.Karanja@kpchr.org
OI Mist, Scott/0000-0001-7992-5345; Maupome, Gerardo/0000-0002-3590-0864
FU NHLBI NIH HHS [U01 HL081624, HL081624]
NR 83
TC 6
Z9 6
U1 3
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 161
EP 174
DI 10.1007/s10935-012-0278-8
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100002
PM 23001689
ER
PT J
AU Adams, A
LaRowe, T
Cronin, K
Prince, R
Wubben, D
Parker, T
Jobe, J
AF Adams, Alexandra K.
LaRowe, Tara L.
Cronin, Kate A.
Prince, Ronald J.
Wubben, Deborah P.
Parker, Tassy
Jobe, Jared B.
TI The Healthy Children, Strong Families Intervention: Design and Community
Participation
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE Obesity; American Indian; Nutrition; Physical activity; Intervention
ID PHYSICAL-ACTIVITY; REPRESENTATIVE SAMPLE; CHILDHOOD OBESITY; DISEASE
RISK; WEIGHT; PREVENTION; PARENTS; PROGRAM; RECALL; YOUTH
AB Healthy Children, Strong Families (HCSF) is a 2-year, community-driven, family-based randomized controlled trial of a healthy lifestyles intervention conducted in partnership with four Wisconsin American Indian tribes. HCSF is composed of 1 year of targeted home visits to deliver nutritional and physical activity curricula. During Year 1, trained community mentors work with 2-5-year-old American Indian children and their primary caregivers to promote goal-based behavior change. During Year 2, intervention families receive monthly newsletters and attend monthly group meetings to participate in activities designed to reinforce and sustain changes made in Year 1. Control families receive only curricula materials during Year 1 and monthly newsletters during Year 2. Each of the two arms of the study comprises 60 families. Primary outcomes are decreased child body mass index (BMI) z-score and decreased primary caregiver BMI. Secondary outcomes include: increased fruit/vegetable consumption, decreased TV viewing, increased physical activity, decreased soda/sweetened drink consumption, improved primary caregiver biochemical indices, and increased primary caregiver self-efficacy to adopt healthy behaviors. Using community-based participatory research and our history of university-tribal partnerships, the community and academic researchers jointly designed this randomized trial. This article describes the study design and data collection strategies, including outcome measures, with emphasis on the communities' input in all aspects of the research.
C1 [Adams, Alexandra K.; LaRowe, Tara L.; Cronin, Kate A.; Prince, Ronald J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI 53715 USA.
[Wubben, Deborah P.] Physicians Plus Insurance Corp, Madison, WI USA.
[Parker, Tassy] Univ New Mexico, Sch Med, Dept Family & Community Med, Albuquerque, NM 87131 USA.
[Jobe, Jared B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Adams, AK (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, 1100 Delaplaine Ct, Madison, WI 53715 USA.
EM alex.adams@fammed.wisc.edu; jobej@mail.nih.gov
FU NHLBI NIH HHS [U-01 HL087381, U01 HL087381]
NR 39
TC 13
Z9 13
U1 3
U2 31
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 175
EP 185
DI 10.1007/s10935-012-0275-y
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100003
PM 22956296
ER
PT J
AU Lee, E
Jobe, J
Yeh, JL
Ali, T
Rhoades, E
Knehans, A
Willis, D
Johnson, M
Zhang, Y
Poolaw, B
Rogers, B
AF Lee, Elisa T.
Jobe, Jared B.
Yeh, Jeunliang
Ali, Tauqeer
Rhoades, Everett R.
Knehans, Allen W.
Willis, Diane J.
Johnson, Melanie R.
Zhang, Ying
Poolaw, Bryce
Rogers, Billy
TI A Cardiovascular Risk Reduction Program for American Indians with
Metabolic Syndrome: The Balance Study
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE CVD prevention; American Indians; Holistic intervention
ID DIETARY MODIFICATION TRIAL; LIFE-STYLE INTERVENTION; PREVENTION PROGRAM;
PHYSICAL-ACTIVITY; CLINICAL-TRIAL; BLOOD-PRESSURE; MISSING DATA;
DISEASE; COMMUNITY; PATTERN
AB The Balance Study is a randomized controlled trial designed to reduce cardiovascular disease (CVD) risk in 200 American Indian (AI) participants with metabolic syndrome who reside in southwestern Oklahoma. Major risk factors targeted include weight, diet, and physical activity. Participants are assigned randomly to one of two groups, a guided or a self-managed group. The guided group attends intervention meetings that comprise education and experience with the following components: diet, exercise, AI culture, and attention to emotional wellbeing. The self-managed group receives printed CVD prevention materials that are generally available. The duration of the intervention is 24 months. Several outcome variables will be compared between the two groups to assess the effectiveness of the intervention program.
C1 [Lee, Elisa T.; Yeh, Jeunliang; Ali, Tauqeer; Rhoades, Everett R.; Willis, Diane J.; Johnson, Melanie R.; Zhang, Ying] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73126 USA.
[Jobe, Jared B.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Knehans, Allen W.] Univ Oklahoma, Hlth Sci Ctr, Dept Nutrit Sci, Coll Allied Hlth, Oklahoma City, OK USA.
[Poolaw, Bryce] Lawton Indian Hosp, Lawton, OK USA.
[Rogers, Billy] Native Workshops, Norman, OK USA.
RP Lee, ET (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73126 USA.
EM elisa-lee@ouhsc.edu
FU NHLBI NIH HHS [U01HL087354, U01 HL087354]
NR 35
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 187
EP 196
DI 10.1007/s10935-012-0273-0
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100004
PM 22941041
ER
PT J
AU Walters, K
LaMarr, J
Levy, R
Pearson, C
Maresca, T
Mohammed, S
Simoni, J
Evans-Campbell, T
Fredriksen-Goldsen, K
Fryberg, S
Jobe, J
AF Walters, Karina L.
LaMarr, June
Levy, Rona L.
Pearson, Cynthia
Maresca, Teresa
Mohammed, Selina A.
Simoni, Jane M.
Evans-Campbell, Teresa
Fredriksen-Goldsen, Karen
Fryberg, Sheryl
Jobe, Jared B.
CA Helidxw Intervention Team
TI Project heli?dx(w)/Healthy Hearts Across Generations: Development and
Evaluation Design of a Tribally Based Cardiovascular Disease Prevention
Intervention for American Indian Families
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE American Indians; Alaska Natives; Cardiovascular; Heart disease;
Intervention; Motivational interviewing
ID PHYSICAL-ACTIVITY; ALASKA NATIVES; MENTAL-HEALTH; OBESITY; RELIABILITY;
COMMUNITY; PARENT; QUESTIONNAIRE; ADOLESCENTS; STRATEGIES
AB American Indian and Alaska Native (AIAN) populations are disproportionately at risk for cardiovascular disease (CVD), diabetes, and obesity, compared with the general US population. This article describes the heli?dx(w)/Healthy Hearts Across Generations project, an AIAN-run, tribally based randomized controlled trial (January 2010-June 2012) designed to evaluate a culturally appropriate CVD risk prevention program for AI parents residing in the Pacific Northwest of the United States. At-risk AIAN adults (n = 135) were randomly assigned to either a CVD prevention intervention arm or a comparison arm focusing on increasing family cohesiveness, communication, and connectedness. Both year-long conditions included 1 month of motivational interviewing counseling followed by personal coach contacts and family life-skills classes. Blood chemistry, blood pressure, body mass index, food intake, and physical activity were measured at baseline and at 4- and 12-month follow-up times.
C1 [Walters, Karina L.; Pearson, Cynthia; Evans-Campbell, Teresa] Univ Washington, Sch Social Work, Indigenous Wellness Res Inst, Seattle, WA 98105 USA.
[LaMarr, June; Fryberg, Sheryl] Tulalip Tribes, Tulalip, WA USA.
[Levy, Rona L.; Fredriksen-Goldsen, Karen] Univ Washington, Sch Social Work, Seattle, WA 98195 USA.
[Maresca, Teresa] Univ Washington, Dept Family Med, Seattle, WA 98195 USA.
[Mohammed, Selina A.] Univ Washington, Bothell Nursing Program, Bothell, WA 98195 USA.
[Simoni, Jane M.] Univ Washington, Dept Psychol, Seattle, WA USA.
[Jobe, Jared B.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Walters, KL (reprint author), Univ Washington, Sch Social Work, Indigenous Wellness Res Inst, 4101 15th Ave NE, Seattle, WA 98105 USA.
EM kw5@uw.edu
FU NHLBI NIH HHS [U01 HL087322, U01-HL 087322]; NICHD NIH HHS [R24
HD042828]; NIDA NIH HHS [K24 DA031613]; NIMH NIH HHS [R25 MH084565];
NIMHD NIH HHS [P60 MD006909]
NR 46
TC 3
Z9 3
U1 3
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 197
EP 207
DI 10.1007/s10935-012-0274-z
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100005
PM 22965622
ER
PT J
AU Henderson, JA
Chubak, J
O'Connell, J
Ramos, MC
Jensen, J
Jobe, JB
AF Henderson, Jeffrey A.
Chubak, Jessica
O'Connell, Joan
Ramos, Maria C.
Jensen, Julie
Jobe, Jared B.
CA LOWPK Project Team
TI Design of a Randomized Controlled Trial of a Web-Based Intervention to
Reduce Cardiovascular Disease Risk Factors Among Remote
Reservation-Dwelling American Indian Adults with Type 2 Diabetes
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE American Indians; Cardiovascular disease; Risk reduction; Intervention;
Web-based
ID IMPAIRED GLUCOSE-TOLERANCE; GLYCEMIC CONTROL; HEALTH; POPULATIONS; CARE;
HEMOGLOBIN; CHALLENGES; MANAGEMENT; PROGRAM
AB We describe a randomized controlled trial, the Lakota Oyate Wicozani Pi Kte (LOWPK) trial, which was designed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease (CVD) among a group of remote reservation-dwelling adult American Indian men and women with type 2 diabetes who are at high risk for CVD. Enrollment on a rolling basis of 180 planned participants began during 2009; an average 18-month follow-up was completed by June 2011. The primary outcome variable is change in glycosylated hemoglobin level after an average 18-month follow-up period. Secondary outcome variables include changes in low-density lipoprotein cholesterol, systolic blood pressure, body mass index, and smoking status, as well as an evaluation of intervention cost-effectiveness. If effective, the LOWPK trial may serve as a guide for future chronic disease intervention trials in remote, technologically challenged settings.
C1 [Henderson, Jeffrey A.; Ramos, Maria C.; Jensen, Julie] Black Hills Ctr Amer Indian Hlth, Rapid City, SD 57701 USA.
[Chubak, Jessica] Grp Hlth Res Inst, Seattle, WA USA.
[O'Connell, Joan] Univ Colorado Denver, Dept Community & Behav Hlth, Colorado Sch Publ Hlth, Aurora, CO USA.
[Jobe, Jared B.] NHLBI, Div Cardiovasc Surg, Bethesda, MD 20892 USA.
RP Henderson, JA (reprint author), Black Hills Ctr Amer Indian Hlth, 701 St Joseph St,Suite 204, Rapid City, SD 57701 USA.
EM jhenderson@bhcaih.org; jobej@mail.nih.gov
FU NHLBI NIH HHS [UO1 HL087422, U01 HL087422]
NR 38
TC 4
Z9 4
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
J9 J PRIM PREV
JI J. Prim. Prev.
PD AUG
PY 2012
VL 33
IS 4
SI SI
BP 209
EP 222
DI 10.1007/s10935-012-0276-x
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014EO
UT WOS:000309358100006
PM 23001642
ER
PT J
AU Chikkaveeraiah, BV
Bhirde, AA
Morgan, NY
Eden, HS
Chen, XY
AF Chikkaveeraiah, Bhaskara V.
Bhirde, Ashwinkumar A.
Morgan, Nicole Y.
Eden, Henry S.
Chen, Xiaoyuan
TI Electrochemical Immunosensors for Detection of Cancer Protein Biomarkers
SO ACS NANO
LA English
DT Review
DE biomarkers; electrochemistry immunoassay; amplification; microfluidics;
nanomaterials; multiplexing
ID PROSTATE-SPECIFIC ANTIGEN; C-REACTIVE PROTEIN; CARBON NANOTUBE FOREST;
ELECTROGENERATED CHEMILUMINESCENCE; ELECTROCHEMILUMINESCENCE
IMMUNOASSAY; BIOELECTROCATALYTIC PROCESSES; HORSERADISH-PEROXIDASE;
MICROFLUIDIC DEVICES; NANOPARTICLE PROBES; PHASE IMMUNOASSAYS
AB Bioanalytical methods have experienced unprecedented growth in recent years, driven in large part by the need for faster, more sensitive, more portable ("point of care") systems to detect protein biomarkers for clinical diagnosis. Electrochemical detection strategies, used in conjunction with immunosensors, offer advantages because they are fast, simple, and low cost. Recent developments in electrochemical immunosensors have significantly improved the sensitivity needed to detect low concentrations of biomarkers present in early stages of cancer. Moreover, the coupling of electrochemical devices with nanomaterials, such as gold nanoparticles, carbon nanotubes, magnetic particles, and quantum dots, offers multiplexing capability for simultaneous measurements of multiple cancer biomarkers. This review will discuss recent advances in the development of electrochemical immunosensors for the next generation of cancer diagnostics, with an emphasis on opportunities for further improvement in cancer diagnostics and treatment monitoring. Details will be given for strategies to increase sensitivity through multilabel amplification, coupled with high densities of capture molecules on sensor surfaces. Such sensors are capable of detecting a wide range of protein quantities, from nanogram to femtogram (depending on the protein biomarkers of interest), in a single sample.
C1 [Chikkaveeraiah, Bhaskara V.; Bhirde, Ashwinkumar A.; Chen, Xiaoyuan] NIBIB, LOMIN, Bethesda, MD 20892 USA.
[Chikkaveeraiah, Bhaskara V.; Morgan, Nicole Y.] NIBIB, Microfabricat & Microfluid Unit, Bethesda, MD 20892 USA.
[Eden, Henry S.] NIBIB, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, LOMIN, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health (NIH); International Cooperative Program of the National Science
Foundation of China (NSFC) [81028009]; Chinese Academy of Sciences
Professorship for Senior International Scientists [2011T2J06]
FX This work was supported by the Intramural Research Program (IRP) of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH), the International Cooperative
Program of the National Science Foundation of China (NSFC) (81028009),
and the Chinese Academy of Sciences Professorship for Senior
International Scientists (2011T2J06)
NR 104
TC 203
Z9 206
U1 63
U2 531
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD AUG
PY 2012
VL 6
IS 8
BP 6546
EP 6561
DI 10.1021/nn3023969
PG 16
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 995DU
UT WOS:000307988900006
PM 22835068
ER
PT J
AU Vilbig, RL
Sarkar, A
Zischkau, J
Knepper, MA
Pisitkun, T
AF Vilbig, Ryan L.
Sarkar, Abhijit
Zischkau, Joseph
Knepper, Mark A.
Pisitkun, Trairak
TI An online tool for calculation of free-energy balance for the renal
inner medulla
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE kidney; mathematical model; urine concentrating mechanism
ID COUNTERCURRENT MULTIPLICATION; COUNTERFLOW SYSTEM; UREA TRANSPORT;
KIDNEY; RAT; VASOPRESSIN; WATER; FLOW
AB Vilbig RL, Sarkar A, Zischkau J, Knepper MA, Pisitkun T. An online tool for calculation of free-energy balance for the renal inner medulla. Am J Physiol Renal Physiol 303: F366-F372, 2012. First published May 30, 2012; doi:10.1152/ajprenal.00147.2012.-Concentrating models of the renal inner medulla can be classified according to external free-energy balance into passive models (positive values) and models that require an external energy source (negative values). Here we introduce an online computational tool that implements the equations of Stephenson and colleagues (Stephenson JL, Tewarson RP, Mejia R. Proc Natl Acad Sci USA 71: 1618-1622, 1974) to calculate external free-energy balance at steady state for the inner medulla (http://helixweb.nih.gov/ESBL/FreeEnergy). Here "external free-energy balance" means the sum of free-energy flows in all streams entering and leaving the inner medulla. The program first assures steady-state mass balance for all components and then tallies net external free-energy balance for the selected flow conditions. Its use is illustrated by calculating external free-energy balance for an example of the passive concentrating model taken from the original paper by Kokko and Rector (Kokko JP, Rector FC Jr. Kidney Int 2: 214-223, 1972).
C1 [Vilbig, Ryan L.; Sarkar, Abhijit; Knepper, Mark A.; Pisitkun, Trairak] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
[Vilbig, Ryan L.; Sarkar, Abhijit; Zischkau, Joseph] Catholic Univ Amer, Dept Phys, Washington, DC 20064 USA.
[Vilbig, Ryan L.; Sarkar, Abhijit; Zischkau, Joseph] Catholic Univ Amer, Vitreous State Lab, Washington, DC 20064 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 National Heart, Lung, and Blood Institute [Z01-HL-001285]; Vitreous
State Lab; Catholic University of America
FX This work was supported by the Intramural Budget of the National Heart,
Lung, and Blood Institute (Project Z01-HL-001285). Funding from Vitreous
State Lab and The Catholic University of America is gratefully
acknowledged.
NR 20
TC 3
Z9 3
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD AUG
PY 2012
VL 303
IS 3
BP F366
EP F372
DI 10.1152/ajprenal.00147.2012
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 984ZA
UT WOS:000307231300006
PM 22647629
ER
PT J
AU Giniger, E
AF Giniger, Edward
TI Notch signaling and neural connectivity
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Review
ID LONG-TERM-MEMORY; CELL FATE; DENDRITIC DEVELOPMENT; SYNAPTIC PLASTICITY;
NEURITE OUTGROWTH; DROSOPHILA BRAIN; DENTATE GYRUS; NEURONS; ACTIVATION;
ABL
AB The cell surface receptor Notch contributes to the development of nearly every tissue in most metazoans by controlling the fates and differentiation of cells. Recent results have now established that Notch also regulates the connectivity of the nervous system, and does so at a variety of levels, including specification of neuronal identity, division, survival and migration, as well as axon guidance, morphogenesis of dendritic arbors and weighting of synapse strength. To these ends, Notch engages at least two signal transduction pathways, one that controls nuclear gene expression and another that directly targets the cytoskeleton. Coordinating the many functions of Notch to produce neural structure is thus a pivotal aspect of building and maintaining the nervous system.
C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Giniger, E (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bldg 35,Rm 1C-1002,35 Convent Dr, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU NINDS, NIH [Z01-NS003013]
FX I thank the members of my lab for many useful discussion and helpful
comments on the manuscript. For critical reading of the manuscript, I
also thank Lavinia Alberi, Nick Gaiano, Matt Kelley, Tadmiri Venkatesh
and Weimin Zhong. This work was supported by the Basic Neuroscience
Program in the Intramural Research Program of the NINDS, NIH
(Z01-NS003013). The funding agency did not influence the content or the
submission of this manuscript.
NR 54
TC 15
Z9 15
U1 0
U2 15
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2012
VL 22
IS 4
BP 339
EP 346
DI 10.1016/j.gde.2012.04.003
PG 8
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 007OW
UT WOS:000308899000006
PM 22608692
ER
PT J
AU Young, MF
Fallon, JR
AF Young, Marian F.
Fallon, Justin R.
TI Biglycan: a promising new therapeutic for neuromuscular and
musculoskeletal diseases
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Editorial Material
ID EXTRACELLULAR-MATRIX; EXPRESSION; BINDS; MICE
C1 [Young, Marian F.] NIH, Bethesda, MD 20892 USA.
[Fallon, Justin R.] Brown Univ, Providence, RI 02912 USA.
RP Young, MF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS; NIAMS NIH HHS [R21 AR055878]; NICHD NIH HHS [R01
HD023924]; NINDS NIH HHS [U01 NS064295]
NR 11
TC 8
Z9 8
U1 0
U2 2
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2012
VL 22
IS 4
BP 398
EP 400
DI 10.1016/j.gde.2012.07.008
PG 3
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 007OW
UT WOS:000308899000014
PM 22841370
ER
PT J
AU Spencer, SP
Belkaid, Y
AF Spencer, Sean P.
Belkaid, Yasmine
TI Dietary and commensal derived nutrients: shaping mucosal and systemic
immunity
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID REGULATORY T-CELLS; VITAMIN-A-DEFICIENCY; RETINOIC-ACID; DENDRITIC
CELLS; GUT MICROBIOTA; SMALL-INTESTINE; TGF-BETA; B-CELLS; RECEPTOR;
RESPONSES
AB The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both dietary and commensal derived signals to guide appropriate function. Recent advances highlight the role of dietary derived nutrients and commensal derived metabolites in shaping gastrointestinal immunity. In particular, vitamin A has been shown to have dominant and pleiotropic effects in the intestine. In addition, dietary derived AHR ligands and commensal derived metabolites are now emerging as important players in mucosa! immunity. Thus nutrition, commensal microflora and the mucosal immune system are all intimately connected.
C1 [Spencer, Sean P.; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Spencer, Sean P.] Univ Penn, Immunol Grad Grp, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Institutes
of Health [5F30DK094708-02]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health and by grant 5F30DK094708-02 from the National Institutes of
Health to SPS. We also thank John R. Grainger, Tim Hand and Nicolas
Bouladoux for their critical reading of the review and graphical
assistance.
NR 55
TC 20
Z9 22
U1 0
U2 17
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2012
VL 24
IS 4
BP 379
EP 384
DI 10.1016/j.coi.2012.07.006
PG 6
WC Immunology
SC Immunology
GA 007OT
UT WOS:000308898700003
PM 22857854
ER
PT J
AU Akbar, AN
Hodes, RJ
AF Akbar, Arne N.
Hodes, Richard J.
TI Immune senescence
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Editorial Material
C1 [Akbar, Arne N.] UCL, Div Infect & Immun, London WC1E 6JF, England.
[Hodes, Richard J.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Akbar, AN (reprint author), UCL, Div Infect & Immun, 5 Univ St, London WC1E 6JF, England.
EM a.akbar@ucl.ac.uk; hodesr@31.nia.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2012
VL 24
IS 4
BP 467
EP 469
DI 10.1016/j.coi.2012.07.002
PG 3
WC Immunology
SC Immunology
GA 007OT
UT WOS:000308898700016
PM 22832007
ER
PT J
AU Weng, NP
AF Weng, Nan-ping
TI Telomeres and immune competency
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID CD8(+) T-LYMPHOCYTES; STEM-CELLS; DYSKERATOSIS-CONGENITA; LENGTH; LIFE;
MECHANISMS; SENESCENCE; DISEASES; HISTORY; BIOLOGY
AB Telomeres are essential for the integrity of chromosomes and for cellular replication. Attrition of telomeres occurs during DNA replication owing to the inability of conventional DNA polymerase to replicate chromosomal termini and the insufficient compensation for telomere loss by telomerase, an enzyme that synthesizes telomeric DNA. A number of genetic defects have been described in humans and in animal models that cause accelerated telomere attrition, in turn leading to severe phenotypes of hematopoietic and other proliferating cells. Telomere length, most frequently measured as an average value in heterogeneous peripheral blood leukocyte populations in humans, has been associated with a wide range of health conditions and diseases of immune and non-immune cells. Here, I review recent studies of telomere length dynamics with particular relevance to immune function.
C1 NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM Wengn@mail.nih.gov
FU National Institute on Aging; National Cancer Institute, National
Institutes of Health (NIH)
FX I thank Richard Hodes for comments and suggestions for this review. This
research was supported by the Intramural Research Programs of the
National Institute on Aging and National Cancer Institute, National
Institutes of Health (NIH).
NR 49
TC 20
Z9 20
U1 0
U2 15
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2012
VL 24
IS 4
BP 470
EP 475
DI 10.1016/j.coi.2012.05.001
PG 6
WC Immunology
SC Immunology
GA 007OT
UT WOS:000308898700017
PM 22626625
ER
PT J
AU Di, L
Artursson, P
Avdeef, A
Ecker, GF
Faller, B
Fischer, H
Houston, JB
Kansy, M
Kerns, EH
Kramer, SD
Lennernas, H
Sugano, K
AF Di, Li
Artursson, Per
Avdeef, Alex
Ecker, Gerhard F.
Faller, Bernard
Fischer, Holger
Houston, J. Brian
Kansy, Manfred
Kerns, Edward H.
Kraemer, Stefanie D.
Lennernas, Hans
Sugano, Kiyohiko
TI Evidence-based approach to assess passive diffusion and carrier-mediated
drug transport
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID MEMBRANE PERMEATION ASSAY; CENTRAL-NERVOUS-SYSTEM; PEPT1 KNOCKOUT MICE;
NEUTRAL AMINO-ACID; LIPID-BILAYERS; P-GLYCOPROTEIN; ARTIFICIAL
MEMBRANES; HYDROPHILIC PORES; TRANSIENT PORES; CACO-2 CELLS
AB Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty speculations are addressed to provide reliable guidance on choosing appropriate tools for drug design and optimization.
C1 [Di, Li] Pfizer Inc, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA.
[Artursson, Per; Lennernas, Hans] Uppsala Univ, Dept Pharm, Biomed Ctr, S-75263 Uppsala, Sweden.
[Avdeef, Alex] in ADME Res, Cambridge, MA 02141 USA.
[Ecker, Gerhard F.] Univ Vienna, Dept Med Chem, A-1090 Vienna, Austria.
[Faller, Bernard] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
[Fischer, Holger; Kansy, Manfred] F Hoffmann La Roche Ltd, Nonclin Safety, CH-4070 Basel, Switzerland.
[Houston, J. Brian] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England.
[Kerns, Edward H.] NIH, Ctr Translat Sci, Rockville, MD 20850 USA.
[Kraemer, Stefanie D.] Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland.
[Sugano, Kiyohiko] Pfizer Inc, Sandwich Labs, Res Formulat, Sandwich CT13 9NJ, Kent, England.
RP Di, L (reprint author), Pfizer Inc, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA.
EM li.di@pfizer.com
OI Ecker, Gerhard/0000-0003-4209-6883; Kramer, Stefanie
D./0000-0002-0426-4340
NR 56
TC 41
Z9 42
U1 8
U2 40
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD AUG
PY 2012
VL 17
IS 15-16
BP 905
EP 912
DI 10.1016/j.drudis.2012.03.015
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 995XO
UT WOS:000308048800014
PM 22507594
ER
PT J
AU Kassis, JA
AF Kassis, Judith A.
TI Transvection in 2012: Site-Specific Transgenes Reveal a Plethora of
Trans-Regulatory Effects
SO GENETICS
LA English
DT Editorial Material
ID REGULATORY DNA; DROSOPHILA; GENE; CHROMOSOME; TRANSCRIPTION; INTEGRASE;
ENHANCERS; PHI-C31; REGION
C1 [Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Kassis, JA (reprint author), NICHD, NIH, 6 Ctr Dr,MSC 2785, Bethesda, MD 20892 USA.
EM jkassis@mail.nih.gov
OI Kassis, Judith/0000-0001-9268-3213
FU Intramural NIH HHS
NR 17
TC 5
Z9 5
U1 0
U2 6
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD AUG
PY 2012
VL 191
IS 4
BP 1037
EP 1039
DI 10.1534/genetics.112.142893
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 009BN
UT WOS:000309000500003
PM 22879406
ER
PT J
AU Sramkova, M
Masedunskas, A
Weigert, R
AF Sramkova, Monika
Masedunskas, Andrius
Weigert, Roberto
TI Plasmid DNA is internalized from the apical plasma membrane of the
salivary gland epithelium in live animals
SO HISTOCHEMISTRY AND CELL BIOLOGY
LA English
DT Article
DE Intravital microscopy; Plasmid DNA; Endocytosis; Salivary glands; Gene
therapy; Non-viral gene delivery
ID COXSACKIE-ADENOVIRUS RECEPTOR; RAT SUBMANDIBULAR-GLAND; MEDIATED
GENE-TRANSFER; IN-VIVO; INTRACELLULAR TRAFFICKING; TRANSGENE EXPRESSION;
INTRAVITAL MICROSCOPY; REGULATED EXOCYTOSIS; AIRWAY EPITHELIA;
PAROTID-GLANDS
AB Non-viral-mediated gene delivery represents an alternative way to express the gene of interest without inducing immune responses or other adverse effects. Understanding the mechanisms by which plasmid DNAs are delivered to the proper target in vivo is a fundamental issue that needs to be addressed in order to design more effective strategies for gene therapy. As a model system, we have used the submandibular salivary glands in live rats and we have recently shown that reporter transgenes can be expressed in different cell populations of the glandular epithelium, depending on the modality of administration of plasmid DNA. Here, by using a combination of immunofluorescence and intravital microscopy, we have explored the relationship between the pattern of transgenes expression and the internalization of plasmid DNA. We found that plasmid DNA is internalized: (1) by all the cells in the salivary gland epithelium, when administered alone, (2) by large ducts, when mixed with empty adenoviral particles, and (3) by acinar cells upon stimulation of compensatory endocytosis. Moreover, we showed that plasmid DNA utilizes different routes of internalization, and evades both the lysosomal degradative pathway and the retrograde pathway towards the Golgi apparatus. This study clearly shows that in vivo approaches have the potential to address fundamental questions on the cellular mechanisms regulating gene delivery.
C1 [Sramkova, Monika; Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 303, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU Intramural Research Program of the NIH, National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research. We would
like to thank Drs. Amornphimoltham and Porat-Shliom for critical reading
of the manuscript.
NR 61
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0948-6143
J9 HISTOCHEM CELL BIOL
JI Histochem. Cell Biol.
PD AUG
PY 2012
VL 138
IS 2
BP 201
EP 213
DI 10.1007/s00418-012-0959-7
PG 13
WC Cell Biology; Microscopy
SC Cell Biology; Microscopy
GA 985EQ
UT WOS:000307246600003
PM 22544351
ER
PT J
AU Huang, WC
Wright, AF
Roman, AJ
Cideciyan, AV
Manson, FD
Gewaily, DY
Schwartz, SB
Sadigh, S
Limberis, MP
Bell, P
Wilson, JM
Swaroop, A
Jacobson, SG
AF Huang, Wei Chieh
Wright, Alan F.
Roman, Alejandro J.
Cideciyan, Artur V.
Manson, Forbes D.
Gewaily, Dina Y.
Schwartz, Sharon B.
Sadigh, Sam
Limberis, Maria P.
Bell, Peter
Wilson, James M.
Swaroop, Anand
Jacobson, Samuel G.
TI RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine
Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CONE-ROD DYSTROPHY; LEBER CONGENITAL AMAUROSIS; OPTICAL COHERENCE
TOMOGRAPHY; RETINITIS-PIGMENTOSA; GENE-THERAPY; IN-VIVO; RPE65
MUTATIONS; DISEASE PROGRESSION; MOUSE MODEL; EXON ORF15
AB PURPOSE. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model.
METHODS. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5-72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset.
RESULTS. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration.
CONCLUSIONS. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. (Invest Ophthalmol Vis Sci. 2012;53:5594-5608) DOI: 10.1167/iovs.12-10070
C1 [Huang, Wei Chieh; Roman, Alejandro J.; Cideciyan, Artur V.; Gewaily, Dina Y.; Schwartz, Sharon B.; Sadigh, Sam; Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Wright, Alan F.; Manson, Forbes D.] Univ Edinburgh, MRC IGMM, MRC, Human Genet Unit, Edinburgh EH8 9YL, Midlothian, Scotland.
[Limberis, Maria P.; Bell, Peter; Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA 19104 USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, SG (reprint author), Univ Penn, Scheie Eye Inst, Dept Ophthalmol, 51 N 39th St, Philadelphia, PA 19104 USA.
EM Alan.Wright@igmm.ed.ac.uk; jacobsos@mail.med.upenn.edu
RI Huang, Wei Chieh/A-1626-2013; Manson, Forbes/G-2222-2015; Wilson,
James/F-9220-2011;
OI Huang, Wei Chieh/0000-0002-7072-996X; Manson,
Forbes/0000-0002-8342-660X; Wilson, James/0000-0002-9630-3131; Swaroop,
Anand/0000-0002-1975-1141
FU Chatlos Foundation; Macula Vision Research Foundation; Hope for Vision;
NEI/NIH [EY017549, RC3 EY020792]; NEI
FX Supported by grants from The Chatlos Foundation, Macula Vision Research
Foundation, Hope for Vision, NEI/NIH (EY017549), NEI/NIH (RC3 EY020792),
and the NEI intramural research program. AVC is a RPB Senior Scientific
Investigator.
NR 59
TC 21
Z9 21
U1 1
U2 11
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2012
VL 53
IS 9
BP 5594
EP 5608
DI 10.1167/iovs.12-10070
PG 15
WC Ophthalmology
SC Ophthalmology
GA 004QE
UT WOS:000308695400064
PM 22807293
ER
PT J
AU Hadden, H
Soldin, SJ
Massaro, D
AF Hadden, Helene
Soldin, Steven J.
Massaro, Donald
TI Circadian disruption alters mouse lung clock gene expression and lung
mechanics
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE clock; corticosterone; impedance; jet lag; body weight
ID CHRONIC JET-LAG; PULMONARY INFLAMMATION; FORCED-OSCILLATIONS; METABOLIC
SYNDROME; SEXUAL-DIMORPHISM; CYSTIC-FIBROSIS; SHIFT WORK; MICE; RHYTHMS;
CHILDREN
AB Hadden H, Soldin SJ, Massaro D. Circadian disruption alters mouse lung clock gene expression and lung mechanics. J Appl Physiol 113: 385-392, 2012. First published June 7, 2012; doi: 10.1152/japplphysiol.00244.2012.-Most aspects of human physiology and behavior exhibit 24-h rhythms driven by a master circadian clock in the brain, which synchronizes peripheral clocks. Lung function and ventilation are subject to circadian regulation and exhibit circadian oscillations. Sleep disruption, which causes circadian disruption, is common in those with chronic lung disease, and in the general population; however, little is known about the effect on the lung of circadian disruption. We tested the hypothesis circadian disruption alters expression of clock genes in the lung and that this is associated with altered lung mechanics. Female and male mice were maintained on a 12: 12-h light/dark cycle (control) or exposed for 4 wk to a shifting light regimen mimicking chronic jet lag (CJL). Airway resistance (Rn), tissue damping (G), and tissue elastance (H) did not differ between control and CJL females. Rn at positive end-expiratory pressure (PEEP) of 2 and 3 cmH(2)O was lower in CJL males compared with controls. G, H, and G/H did not differ between CJL and control males. Among CJL females, expression of clock genes, Bmal1 and Rev-erb alpha, was decreased; expression of their repressors, Per2 and Cry 2, was increased. Among CJL males, expression of Clock was decreased; Per 2 and Rev-erb alpha expression was increased. We conclude circadian disruption alters lung mechanics and clock gene expression and does so in a sexually dimorphic manner.
C1 [Hadden, Helene; Massaro, Donald] Georgetown Univ, Sch Med, Lung Regenerat Lab, Dept Med, Washington, DC 20057 USA.
[Soldin, Steven J.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Massaro, D (reprint author), Georgetown Univ, Sch Med, Lung Regenerat Lab, Dept Med, 3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM massarod@georgetown.edu
FU National Heart, Lung, and Blood Institute Grant [HL-020366-33]
FX This study was supported by National Heart, Lung, and Blood Institute
Grant HL-020366-33.
NR 58
TC 10
Z9 10
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD AUG
PY 2012
VL 113
IS 3
BP 385
EP 392
DI 10.1152/japplphysiol.00244.2012
PG 8
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 984XG
UT WOS:000307226000005
PM 22678966
ER
PT J
AU Abhyankar, S
Demner-Fushman, D
McDonald, CJ
AF Abhyankar, Swapna
Demner-Fushman, Dina
McDonald, Clement J.
TI Standardizing clinical laboratory data for secondary use
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Vocabulary standards; Laboratory tests; LOINC; MIMIC-II; Secondary use;
Mapping guidelines
ID RECORDS; RISK
AB Clinical databases provide a rich source of data for answering clinical research questions. However, the variables recorded in clinical data systems are often identified by local, idiosyncratic, and sometimes redundant and/or ambiguous names (or codes) rather than unique, well-organized codes from standard code systems. This reality discourages research use of such databases, because researchers must invest considerable time in cleaning up the data before they can ask their first research question. Researchers at MIT developed MIMIC-II, a nearly complete collection of clinical data about intensive care patients. Because its data are drawn from existing clinical systems, it has many of the problems described above. In collaboration with the MIT researchers, we have begun a process of cleaning up the data and mapping the variable names and codes to LOINC codes. Our first step, which we describe here, was to map all of the laboratory test observations to LOINC codes. We were able to map 87% of the unique laboratory tests that cover 94% of the total number of laboratory tests results. Of the 13% of tests that we could not map, nearly 60% were due to test names whose real meaning could not be discerned and 29% represented tests that were not yet included in the LOINC table. These results suggest that LOINC codes cover most of laboratory tests used in critical care. We have delivered this work to the MIMIC-II researchers, who have included it in their standard MIMIC-II database release so that researchers who use this database in the future will not have to do this work. Published by Elsevier Inc.
C1 [Abhyankar, Swapna; Demner-Fushman, Dina; McDonald, Clement J.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Abhyankar, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,Bldg 38A-7N707, Bethesda, MD 20894 USA.
EM swapna.abhyankar@nih.gov; dina.demner@nih.gov; clement.mcdonald@nih.gov
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Library of Medicine, National Institutes of Health.
NR 22
TC 10
Z9 10
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2012
VL 45
IS 4
SI SI
BP 642
EP 650
DI 10.1016/j.jbi.2012.04.012
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 998RN
UT WOS:000308258200005
PM 22561944
ER
PT J
AU Lin, MC
Vreeman, DJ
McDonald, CJ
Huff, SM
AF Lin, M. C.
Vreeman, D. J.
McDonald, Clement J.
Huff, S. M.
TI Auditing consistency and usefulness of LOINC use among three large
institutions - Using version spaces for grouping LOINC codes
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Controlled vocabulary; LOINC; Evaluation research; Clinical laboratory
information systems; LOINC usage; Consistency; Usefulness; Semantic
interoperability; LOINC usage; Data exchange standards
ID OBSERVATION IDENTIFIER NAMES; DATA SETS; TERMINOLOGY; SYSTEMS; FRAMEWORK
AB Objectives: We wanted to develop a method for evaluating the consistency and usefulness of LOINC code use across different institutions, and to evaluate the degree of interoperability that can be attained when using LOINC codes for laboratory data exchange. Our specific goals were to: (1) Determine if any contradictory knowledge exists in LOINC. (2) Determine how many LOINC codes were used in a truly interoperable fashion between systems. (3) Provide suggestions for improving the semantic interoperability of LOINC.
Methods: We collected Extensional Definitions (EDs) of LOINC usage from three institutions. The version space approach was used to divide LOINC codes into small sets, which made auditing of LOINC use across the institutions feasible. We then compared pairings of LOINC codes from the three institutions for consistency and usefulness.
Results: The number of LOINC codes evaluated were 1917, 1267 and 1693 as obtained from ARUP, Intermountain and Regenstrief respectively. There were 2022, 2030, and 2301 version spaces among ARUP and Intermountain, Intermountain and Regenstrief and ARUP and Regenstrief respectively. Using the EDs as the gold standard, there were 104, 109 and 112 pairs containing contradictory knowledge and there were 1165, 765 and 1121 semantically interoperable pairs. The interoperable pairs were classified into three levels: (1) Level I - No loss of meaning, complete information was exchanged by identical codes. (2) Level II - No loss of meaning, but processing of data was needed to make the data completely comparable. (3) Level III - Some loss of meaning. For example, tests with a specific 'method' could be rolled-up with tests that were 'methodless'.
Conclusions: There are variations in the way LOINC is used for data exchange that result in some data not being truly interoperable across different enterprises. To improve its semantic interoperability, we need to detect and correct any contradictory knowledge within LOINC and add computable relationships that can be used for making reliable inferences about the data. The LOINC committee should also provide detailed guidance on best practices for mapping from local codes to LOINC codes and for using LOINC codes in data exchange. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Lin, M. C.; Huff, S. M.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
[Vreeman, D. J.] Regenstrief Inst Inc, Indianapolis, IN USA.
[Vreeman, D. J.] Indiana Univ Sch Med, Indianapolis, IN USA.
[Huff, S. M.] Intermt Healthcare, Salt Lake City, UT USA.
[McDonald, Clement J.] Natl Lib Med, Lister Hill Ctr, Washington, DC USA.
RP Huff, SM (reprint author), S Off Bldg,5171 S Cottonwood St, Murrary, UT 84107 USA.
EM stan.huff@imail.org
FU Intramural NIH HHS [Z99 LM999999]
NR 28
TC 7
Z9 7
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 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2012
VL 45
IS 4
SI SI
BP 658
EP 666
DI 10.1016/j.jbi.2012.01.008
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 998RN
UT WOS:000308258200007
PM 22306382
ER
PT J
AU Vreeman, DJ
Chiaravalloti, MT
Hook, J
McDonald, CJ
AF Vreeman, Daniel J.
Chiaravalloti, Maria Teresa
Hook, John
McDonald, Clement J.
TI Enabling international adoption of LOINC through translation
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE LOINC; Vocabulary, controlled; Multilingualism; Translating; Clinical
laboratory information systems/standards; Medical records systems;
Computerized/standards
ID OBSERVATION IDENTIFIER NAMES; CODES LOINC; INSTITUTIONS; SYSTEMS
AB Interoperable health information exchange depends on adoption of terminology standards, but international use of such standards can be challenging because of language differences between local concept names and the standard terminology. To address this important barrier, we describe the evolution of an efficient process for constructing translations of LOINC terms names, the foreign language functions in RELMA, and the current state of translations in LOINC. We also present the development of the Italian translation to illustrate how translation is enabling adoption in international contexts. We built a tool that finds the unique list of LOINC Parts that make up a given set of LOINC terms. This list enables translation of smaller pieces like the core component "hepatitis c virus" separately from all the suffixes that could appear with it, such "Ab.IgG", "DNA", and "RNA". We built another tool that generates a translation of a full LOINC name from all of these atomic pieces. As of version 2.36 (June 2011), LOINC terms have been translated into nine languages from 15 linguistic variants other than its native English. The five largest linguistic variants have all used the Part-based translation mechanism. However, even with efficient tools and processes, translation of standard terminology is a complex undertaking. Two of the prominent linguistic challenges that translators have faced include: the approach to handling acronyms and abbreviations, and the differences in linguistic syntax (e.g. word order) between languages. LOINC's open and customizable approach has enabled many different groups to create translations that met their needs and matched their resources. Distributing the standard and its many language translations at no cost worldwide accelerates LOINC adoption globally, and is an important enabler of interoperable health information exchange. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Vreeman, Daniel J.; Hook, John] Regenstrief Inst Inc, Indianapolis, IN 46202 USA.
[Vreeman, Daniel J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Chiaravalloti, Maria Teresa] Univ Calabria, Dipartimento Linguist, Lab Documentaz, I-87036 Arcavacata Di Rende, CS, Italy.
[McDonald, Clement J.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Vreeman, DJ (reprint author), Regenstrief Inst Inc, 410 W 10th St,Suite 2000, Indianapolis, IN 46202 USA.
EM dvreeman@regenstrief.org
OI CHIARAVALLOTI, MARIATERESA/0000-0003-4695-2026
FU Consiglio Nazionale delle Ricerche (CNR), Information and Communication
Technology Department, Italy; National Library of Medicine
[HHSN2762008000006C]
FX The authors thank Mark Fisher for technical assistance; Lone Carey,
Beverly Knight, and Lin Zhang for providing feedback on the LOINC
translation process, Giuseppe Alfredo Cavarretta for his support of the
Italian LOINC effort, and all of the other individuals who have
contributed to a LOINC translation. This work was performed at the
Regenstrief Institute, Indianapolis, IN, USA and Laboratorio di
Documentazione, Dipartimento di Linguistica dell'Universita della
Calabria, Italy, in partnership with Azienda Ospedaliero-Universitaria
Molinette, Torino, Italy. It was supported by Consiglio Nazionale delle
Ricerche (CNR), Information and Communication Technology Department,
Italy and by contract HHSN2762008000006C from the National Library of
Medicine.
NR 24
TC 12
Z9 12
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2012
VL 45
IS 4
SI SI
BP 667
EP 673
DI 10.1016/j.jbi.2012.01.005
PG 7
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 998RN
UT WOS:000308258200008
PM 22285984
ER
PT J
AU Reich, C
Ryan, PB
Stang, PE
Rocca, M
AF Reich, Christian
Ryan, Patrick B.
Stang, Paul E.
Rocca, Mitra
TI Evaluation of alternative standardized terminologies for medical
conditions within a network of observational healthcare databases
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Terminology standards; Coding scheme; Vocabulary; Taxonomy; Mapping;
ICD-9-CM
ID COMMON DATA MODEL; SAFETY SURVEILLANCE; INFORMATICS ASSOCIATION;
LANGUAGE SYSTEM; FRAMEWORK
AB Large electronic databases of health care information, such as administrative claims and electronic health records, are available and are being used in a number of public health settings, including drug safety surveillance. However, because of a lack of standardization, clinical terminologies may differ across databases. With the aid of existing resources and expert coders, we have developed mapping tables to convert ICD-9-CM diagnosis codes used in some existing databases to SNOMED-CT and MedDRA. In addition, previously developed definitions for specific health outcomes of interest were mapped to the same standardized vocabularies. We evaluated how vocabulary mapping affected (1) the retention of clinical data from two test databases, (2) the semantic space of outcome definitions, (3) the prevalence of each outcome in the test databases, and (4) the reliability of analytic methods designed to detect drug-outcome associations in the test databases. Although vocabulary mapping affected the semantic space of some outcome definitions, as well as the prevalence of some outcomes in the test databases, it had only minor effects on the analysis of drug-outcome associations. Furthermore, both SNOMED-CT and MedDRA were viable for use as standardized vocabularies in systems designed to perform active medical product surveillance using disparate sources of observational data. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Reich, Christian; Ryan, Patrick B.; Stang, Paul E.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD 20814 USA.
[Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
[Rocca, Mitra] US FDA, Off Translat Sci, CDER, Silver Spring, MD 20933 USA.
RP Reich, C (reprint author), Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, 9650 Rockville Pike, Bethesda, MD 20814 USA.
EM reich@omop.org; ryan@omop.org; PStang@its.jnj.com;
mitra.rocca@fda.hhs.gov
FU Foundation for the National Institutes of Health
FX The Observational Medical Outcomes Partnership is funded by the
Foundation for the National Institutes of Health through generous
contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer
Healthcare Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly &
Company, GlaxoSmithlaine, Johnson & Johnson, Lundbeck, Inc., Merck &
Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc,
Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi,
Schering-Plough Corporation, and Takeda. Assistance with writing and
manuscript preparation was provided by Ken Scholz, PhD, with financial
support from the Foundation for the National Institutes of Health.
NR 24
TC 16
Z9 16
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 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2012
VL 45
IS 4
SI SI
BP 689
EP 696
DI 10.1016/j.jbi.2012.05.002
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 998RN
UT WOS:000308258200011
PM 22683994
ER
PT J
AU Del Fiol, G
Huser, V
Strasberg, HR
Maviglia, SM
Curtis, C
Cimino, JJ
AF Del Fiol, Guilherme
Huser, Vojtech
Strasberg, Howard R.
Maviglia, Saverio M.
Curtis, Clayton
Cimino, James J.
TI Implementations of the HL7 Context-Aware Knowledge Retrieval
("Infobutton") Standard: Challenges, strengths, limitations, and uptake
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Information need; Health information technology; Standard; Clinical
decision support; Electronic health record system; Knowledge resource
ID INFORMATION NEEDS; PHYSICIANS
AB To support clinical decision-making, computerized information retrieval tools known as "infobuttons" deliver contextually-relevant knowledge resources into clinical information systems. The Health Level Seven International (HL7) Context-Aware Knowledge Retrieval (Infobutton) Standard specifies a standard mechanism to enable infobuttons on a large scale. Objective: To examine the experience of organizations in the course of implementing the HL7 Infobutton Standard.
Method: Cross-sectional online survey and in-depth phone interviews.
Results: A total of 17 organizations participated in the study. Analysis of the in-depth interviews revealed 20 recurrent themes. Implementers underscored the benefits, simplicity, and flexibility of the HL7 Infobutton Standard. Yet, participants voiced the need for easier access to standard specifications and improved guidance to beginners. Implementers predicted that the Infobutton Standard will be widely or at least fairly well adopted in the next 5 years, but uptake will depend largely on adoption among electronic health record (EHR) vendors. To accelerate EHR adoption of the Infobutton Standard, implementers recommended HL7-compliant infobutton capabilities to be included in the United States Meaningful Use Certification Criteria for EHR systems. Limitations: Opinions and predictions should be interpreted with caution, since all the participant organizations have successfully implemented the standard and over half of the organizations were actively engaged in the development of the standard.
Conclusion: Overall, implementers reported a very positive experience with the HL7 Infobutton Standard. Despite indications of increasing uptake, measures should be taken to stimulate adoption of the Infobutton Standard among EHR vendors. Widespread adoption of the Infobutton Standard has the potential to bring contextually relevant clinical decision support content into the healthcare provider workflow. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Del Fiol, Guilherme] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA.
[Huser, Vojtech; Cimino, James J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Strasberg, Howard R.] Wolters Kluwer Hlth, San Diego, CA USA.
[Maviglia, Saverio M.] Partners Healthcare, Wellesley, MA USA.
[Curtis, Clayton] Dept Vet Affairs, Boston, MA USA.
RP Del Fiol, G (reprint author), Univ Utah, Dept Biomed Informat, HSEB 5700,26 South 2000 East, Salt Lake City, UT 84112 USA.
EM guilherme.delfiol@utah.edu
OI Cimino, James/0000-0003-4101-1622; Del Fiol,
Guilherme/0000-0001-9954-6799
FU Agency for Healthcare Research and Quality [K01HS018352]; NIH Clinical
Center; National Library of Medicine
FX The authors would like to acknowledge all the individuals who helped
develop the HL7 Context-Aware Knowledge Retrieval Standard. We would
also like to recognize the individuals who participated in the study
interviews and the organizations that they represented. This project was
supported in part by Grant Number K01HS018352 from the Agency for
Healthcare Research and Quality. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the Agency for Healthcare Research and Quality. This
research was also supported in part by the Intramural Research Program
of the NIH Clinical Center and the National Library of Medicine.
NR 30
TC 23
Z9 23
U1 4
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD AUG
PY 2012
VL 45
IS 4
SI SI
BP 726
EP 735
DI 10.1016/j.jbi.2011.12.006
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 998RN
UT WOS:000308258200016
PM 22226933
ER
PT J
AU Peel, N
Dougherty, M
Goeres, J
Liu, Y
O'Connell, KF
AF Peel, Nina
Dougherty, Michael
Goeres, Jacqueline
Liu, Yan
O'Connell, Kevin F.
TI The C. elegans F-box proteins LIN-23 and SEL-10 antagonize centrosome
duplication by regulating ZYG-1 levels
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE F-box; ZYG-1; Centrosome
ID PLK4-RELATED KINASE ZYG-1; CAENORHABDITIS-ELEGANS; CENTRIOLE
DUPLICATION; UBIQUITIN LIGASE; CYCLIN-E; CHROMOSOMAL INSTABILITY;
MEDIATED DEGRADATION; CELL-DIVISION; IN-VIVO; PHOSPHORYLATION
AB The correct segregation of DNA during cell division requires formation of a bipolar spindle, organized at each pole by a centrosome. The regulation of centrosome duplication such that each mitotic cell has exactly two centrosomes is therefore of central importance to cell division. Deregulation of centrosome duplication causes the appearance of supernumerary centrosomes, which are a hallmark of many cancer cells and can contribute to tumorigenesis. Overexpression of the kinase Plk4, which is required for centrosome duplication, causes the formation of extra centrosomes, and aberrant Plk4 expression levels are associated with cancer. Data from Drosophila and human cells show that Plk4 levels are regulated by the SCF ubiquitin ligase and proteasomal degradation. Recognition of Plk4 by the SCF complex is mediated by the F-box protein Slimb/beta TrCP. We show that levels of the C. elegans Plk4 homolog ZYG-1 are elevated by impairing proteasome or SCF function, indicating that ZYG-1 is regulated by a conserved mechanism. In C. elegans, similar to Drosophila and humans, we find that the Slimb/bTrCP homolog LIN-23 regulates ZYG-1 levels. In addition, we show that a second F-box protein, SEL-10, also contributes to ZYG-1 regulation. Co-depletion of LIN-23 and SEL-10 suggests these proteins function cooperatively. Because SEL-10 is the homolog of human FBW7, which is frequently mutated in cancer, our findings have implications for understanding tumorigenesis.
C1 [Peel, Nina] Coll New Jersey, Dept Biol, Ewing, NJ 08628 USA.
[Dougherty, Michael; Goeres, Jacqueline; Liu, Yan; O'Connell, Kevin F.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Peel, N (reprint author), Coll New Jersey, Dept Biol, Ewing, NJ 08628 USA.
EM peeln@tcnj.edu; kevino@intra.niddk.nih.gov
OI Peel, Nina/0000-0002-4277-4106
FU National Institutes of Health; National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of Diabetes and
Digestive and Kidney Diseases. Deposited in PMC for release after 12
months.
NR 53
TC 12
Z9 19
U1 0
U2 0
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD AUG 1
PY 2012
VL 125
IS 15
BP 3535
EP 3544
DI 10.1242/jcs.097105
PG 10
WC Cell Biology
SC Cell Biology
GA 010PE
UT WOS:000309105800006
PM 22623721
ER
PT J
AU Brown, RJ
Rother, KI
AF Brown, Rebecca J.
Rother, Kristina I.
TI Non-Nutritive Sweeteners and their Role in the Gastrointestinal Tract
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Review
ID STIMULATES INSULIN-SECRETION; PANCREATIC BETA-CELLS; TASTE RECEPTORS;
ARTIFICIAL SWEETENERS; METABOLIC SYNDROME; BODY-WEIGHT;
GLUCOSE-ABSORPTION; SUGAR ABSORPTION; ENERGY-BALANCE; DIETARY-INTAKE
AB Context: Non-nutritive sweeteners can bind to sweet-taste receptors present not only in the oral cavity, but also on enteroendocrine and pancreatic islet cells. Thus, these sweeteners may have biological activity by eliciting or inhibiting hormone secretion. Because consumption of non-nutritive sweeteners is common in the United States, understanding the physiological effects of these substances is of interest and importance.
Evidence Acquisition: A PubMed (1960-2012) search was performed to identify articles examining the effects of non-nutritive sweeteners on gastrointestinal physiology and hormone secretion.
Evidence Synthesis: The majority of in vitro studies showed that non-nutritive sweeteners can elicit secretion of gut hormones such as glucagon-like peptide 1 and glucose-dependent insulinotropic peptide in enteroendocrine or islet cells. In rodents, non-nutritive sweeteners increased the rate of intestinal glucose absorption, but did not alter gut hormone secretion in the absence of glucose. Most studies in humans have not detected effects of non-nutritive sweeteners on gut hormones or glucose absorption. Of eight human studies, one showed increased glucose-stimulated glucagon-like peptide 1 secretion after diet soda consumption, and one showed decreased glucagon secretion after stevia ingestion.
Conclusions: In humans, few studies have examined the hormonal effects of non-nutritive sweeteners, and inconsistent results have been reported, with the majority not recapitulating in vitro data. Further research is needed to determine whether non-nutritive sweeteners have physiologically significant biological activity in humans. (J Clin Endocrinol Metab 97: 2597-2605, 2012)
C1 [Brown, Rebecca J.; Rother, Kristina I.] NIDDKD, Bethesda, MD 20892 USA.
RP Brown, RJ (reprint author), Bldg 10,Room 7C-432A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM brownrebecca@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 60
TC 30
Z9 30
U1 3
U2 86
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2012
VL 97
IS 8
BP 2597
EP 2605
DI 10.1210/jc.2012-1475
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 987ZI
UT WOS:000307457400037
PM 22679063
ER
PT J
AU Balasubramaniam, S
Ron, E
Gridley, G
Schneider, AB
Brenner, AV
AF Balasubramaniam, Sanjeeve
Ron, Elaine
Gridley, Gloria
Schneider, Arthur B.
Brenner, Alina V.
TI Association between Benign Thyroid and Endocrine Disorders and
Subsequent Risk of Thyroid Cancer among 4.5 Million U.S. Male Veterans
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID UNITED-STATES POPULATION; SERUM TSH; INCREASING INCIDENCE; IODINE
DEFICIENCY; NATIONAL-HEALTH; POOLED ANALYSIS; AUTOIMMUNITY; OUTCOMES;
NODULE; RACE
AB Context: Risk factors for thyroid cancer (TC) in males are poorly understood.
Objectives, Setting, and Participants: Our aim was to evaluate the relationship between history of benign thyroid and endocrine disorders and risk of TC among 4.5 million male veterans admitted to U. S. Veterans Affairs hospitals between July 1, 1969, and September 30, 1996.
Design: We conducted a retrospective cohort study based on hospital discharge records with 1053 cases of TC.
Main Outcome Measures: We estimated relative risks (RR) and computed 95% confidence intervals (CI) for TC using time-dependent Poisson regression models. To evaluate potential ascertainment bias and/or delayed diagnosis of TC, we also analyzed RR by time between diagnosis of benign disorder and TC (<5 or >= 5 yr).
Results: RR for TC were significantly elevated with many disorders and were often higher less than 5 yr compared with 5 yr or more before TC diagnosis. RR (95% CI) less than 5 yr/at least 5 yr were 67.9 (42.4-108.8)/28.9 (9.2-90.2) for thyroid adenoma, 77.8 (64.5-93.1)/25.9 (17.9-38.0) for nontoxic nodular goiter, 23.9 (13.8-41.3)/12.9 (4.8-34.4) for thyroiditis, 8.8 (6.9-11.3)/6.0 (3.8-9.6) for hypothyroidism, 6.4 (4.4-9.4)/2.0 (0.8-4.8) for thyrotoxicosis, and 1.2 (1.0-1.4)/1.1 (0.9-1.5) for diabetes. For some disorders, RR also significantly varied by attained age and race with younger patients and Blacks having higher RR than older patients and Whites.
Conclusions: We found strong associations for a history of thyroid adenoma, nodular goiter, thyroiditis, or hypothyroidism with TC in males allowing for increased surveillance/delayed diagnosis and evidence that some of these associations are modified by age and race. (J Clin Endocrinol Metab 97: 2661-2669, 2012)
C1 [Balasubramaniam, Sanjeeve] NCI, Canc Prevent Fellowship Program, NIH, DHHS, Bethesda, MD 20902 USA.
[Balasubramaniam, Sanjeeve] NCI, Med Oncol Branch, NIH, DHHS, Bethesda, MD 20902 USA.
[Ron, Elaine; Gridley, Gloria; Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Schneider, Arthur B.] Univ Illinois, Coll Med, Sect Endocrinol Diabet & Metab, Chicago, IL 60612 USA.
RP Balasubramaniam, S (reprint author), Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM balas@nih.gov
OI Balasubramaniam, Sanjeeve/0000-0002-0643-2117
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services.
NR 40
TC 9
Z9 9
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2012
VL 97
IS 8
BP 2661
EP 2669
DI 10.1210/jc.2011-2996
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 987ZI
UT WOS:000307457400049
PM 22569239
ER
PT J
AU de Jonge, L
Zhao, XC
Mattingly, MS
Zuber, SM
Piaggi, P
Csako, G
Cizza, G
AF de Jonge, Lilian
Zhao, Xiongce
Mattingly, Megan S.
Zuber, Samuel M.
Piaggi, Paolo
Csako, Gyorgy
Cizza, Giovanni
CA NIDDK Sleep Extension Study Grp
TI Poor Sleep Quality and Sleep Apnea Are Associated with Higher Resting
Energy Expenditure in Obese Individuals with Short Sleep Duration
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID AIRWAY PRESSURE THERAPY; INDIRECT CALORIMETRY; CONTROLLED-TRIAL;
WEIGHT-GAIN; FOOD-INTAKE; MEN; INSOMNIA; DEPRIVATION; STRESS; ADULTS
AB Context: Epidemiological studies reported an inverse or U-shaped relationship between sleep duration and weight. The relationship between sleep and resting energy expenditure (REE) has not been well characterized.
Objective: The aim of the study was to determine the relationship between sleep, REE, and stress hormones.
Design and Setting: We conducted a cross-sectional evaluation of a prospective cohort study at a tertiary referral research clinical center.
Subjects: Subjects included 126 obese individuals (30 males, 96 females; age, 40.5 +/- 6.9 yr; body mass index, 38.6 +/- 6.5 kg/m(2); sleep duration, 360 +/- 50 min/night; and sleep efficiency, 79.5 +/- 7.5%).
Main Outcome Measure(s): REE and respiratory quotient (RQ) were assessed by indirect calorimetry. Sleep duration and sleep efficiency were assessed by actigraphy. Sleep quality was estimated by questionnaires, and sleep apnea was evaluated by respiratory disturbance index (RDI). Morning plasma ACTH, serum cortisol, and 24-h urinary free cortisol and catecholamines were also measured.
Results: RDI was positively correlated with REE adjusted by fat-free mass (r = 0.307; P = 0.003) and RQ (r = 0.377; P < 0.001). Sleep efficiency was inversely correlated with RQ (r = -0.200; P = 0.033). The relationship of RDI score and REE was stronger in men than women (P = 0.03). In women, serum cortisol was positively correlated (r = 0.407; P < 0.001), and Epworth sleepiness score tended to be inversely (r = -0.190; P = 0.086) correlated with adjusted REE. The RQ was positively related to RDI in women, whereas subjective sleep time was related to RQ in men. In a multiple regression model, RDI, serum cortisol, and urinary norepinephrine were directly related to REE, whereas serum cortisol also directly related to adjusted REE.
Conclusion: Poor sleep quality was associated with increased REE, a higher RQ indicating a shift from fat toward carbohydrate oxidation, and activation of the stress system. (J Clin Endocrinol Metab 97: 2881-2889, 2012)
C1 [de Jonge, Lilian; Zhao, Xiongce; Mattingly, Megan S.; Zuber, Samuel M.; Cizza, Giovanni] NIDDKD, Sect Neuroendocrinol Obes, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Piaggi, Paolo] Univ Hosp Pisa, Dept Endocrinol & Kidney, I-56126 Pisa, Italy.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), Clin Res Ctr, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA.
EM cizzag@intra.niddk.nih.gov
OI de Jonge, Lilian/0000-0001-5900-0695; Piaggi, Paolo/0000-0003-2774-9161
FU Intramural Programs of the National Institute of Diabetes, Digestive,
and Kidney Diseases (NIDDK); Clinical Center, National Institutes of
Health (NIH); NIDDK [06-DK-0036]
FX This study was supported by the Intramural Programs of the National
Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK), and the
Clinical Center, National Institutes of Health (NIH). This study was
conducted under the NIDDK protocol 06-DK-0036 and is listed in
www.ClinicalTrials.gov (identifier: NCT00261898). Statistical expertise
and a central sample-handling and assays facility are provided by the
NIDDK Intramural Obesity Initiative of the NIH Clinical Center.
NR 48
TC 10
Z9 10
U1 0
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2012
VL 97
IS 8
BP 2881
EP 2889
DI 10.1210/jc.2011-2858
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 987ZI
UT WOS:000307457400074
PM 22689694
ER
PT J
AU Charmandari, E
Sertedaki, A
Kino, T
Merakou, C
Hoffman, DA
Hatch, MM
Hurt, DE
Lin, L
Xekouki, P
Stratakis, CA
Chrousos, GP
AF Charmandari, Evangelia
Sertedaki, Amalia
Kino, Tomoshige
Merakou, Christina
Hoffman, Dax A.
Hatch, Michael M.
Hurt, Darrell E.
Lin, Lin
Xekouki, Paraskevi
Stratakis, Constantine A.
Chrousos, George P.
TI A Novel Point Mutation in the KCNJ5 Gene Causing Primary
Hyperaldosteronism and Early-Onset Autosomal Dominant Hypertension
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM; FAMILIAL HYPERALDOSTERONISM; K+
CHANNEL; GLOMERULOSA CELLS; ANGIOTENSIN-II; HEREDITARY HYPERTENSION;
POTASSIUM CHANNELS; SIGNALING PATHWAYS; PROTEIN-STRUCTURE;
ADRENAL-CORTEX
AB Context: Aldosterone production in the adrenal zona glomerulosa is mainly regulated by angiotensin II, [K+], and ACTH. Genetic deletion of subunits of K+-selective leak (KCNK) channels TWIK-related acid sensitive K+-1 and/or TWIK-related acid sensitive K+-3 in mice results in primary hyperaldosteronism, whereas mutations in the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene are implicated in primary hyperaldosteronism and, in certain cases, in autonomous glomerulosa cell proliferation in humans.
Objective: The objective of the study was to investigate the role of KCNK3, KCNK5, KCNK9, and KCNJ5 genes in a family with primary hyperaldosteronism and early-onset hypertension.
Patients and Methods: Two patients, a mother and a daughter, presented with severe primary hyperaldosteronism, bilateral massive adrenal hyperplasia, and early-onset hypertension refractory to medical treatment. Genomic DNA was isolated and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials.
Results: Sequencing of the KCNJ5 gene revealed a single, heterozygous guanine to thymine (G -> T) substitution at nucleotide position 470 (n.G470T), resulting in isoleucine (I) to serine (S) substitution at amino acid 157 (p.I157S). This mutation results in loss of ion selectivity, cell membrane depolarization, increased Ca2+ entry in adrenal glomerulosa cells, and increased aldosterone synthesis. Sequencing of the KCNK3, KCNK5, and KCNK9 genes revealed no mutations in our patients.
Conclusions: These findings explain the pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive aldosterone production. (J Clin Endocrinol Metab 97: E1532-E1539, 2012)
C1 [Charmandari, Evangelia; Sertedaki, Amalia; Merakou, Christina; Chrousos, George P.] Univ Athens, Sch Med, Div Endocrinol Metab & Diabet, Aghia Sophia Childrens Hosp,Dept Pediat 1, GR-11527 Athens, Greece.
[Charmandari, Evangelia; Sertedaki, Amalia; Chrousos, George P.] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece.
[Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Bethesda, MD 20892 USA.
[Hoffman, Dax A.; Hatch, Michael M.; Lin, Lin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
[Xekouki, Paraskevi; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Charmandari, E (reprint author), Univ Athens, Sch Med, Div Endocrinol Metab & Diabet, Aghia Sophia Childrens Hosp,Dept Pediat 1, Thivon & Papadiamantopoulou St, GR-11527 Athens, Greece.
EM evangelia.charmandari@googlemail.com
RI Charmandari, Evangelia/B-6701-2011; Hoffman, Dax/E-5155-2011; Hurt,
Darrell/B-5076-2013
OI Hoffman, Dax/0000-0001-6999-2157; Hurt, Darrell/0000-0002-9829-8567
FU University of Athens Medical School (Athens, Greece); Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institute of Allergy and Infectious Diseases (National
Institutes of Health, Bethesda, MD)
FX This work was supported in part by the University of Athens Medical
School (Athens, Greece), the intramural program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, and
the National Institute of Allergy and Infectious Diseases (National
Institutes of Health, Bethesda, MD).
NR 40
TC 50
Z9 53
U1 0
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2012
VL 97
IS 8
BP E1532
EP E1539
DI 10.1210/jc.2012-1334
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 987ZI
UT WOS:000307457400023
PM 22628607
ER
PT J
AU Kino, T
Pavlatou, MG
Moraitis, AG
Nemery, RL
Raygada, M
Stratakis, CA
AF Kino, Tomoshige
Pavlatou, Maria G.
Moraitis, Andreas G.
Nemery, Robin L.
Raygada, Margarita
Stratakis, Constantine A.
TI ZNF764 Haploinsufficiency May Explain Partial Glucocorticoid, Androgen,
and Thyroid Hormone Resistance Associated with 16p11.2 Microdeletion
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NUCLEAR RECEPTORS; TIF1 ALPHA; GENE; INDIVIDUALS; DELETIONS; DOMAINS;
FAMILY; AUTISM; BETA
AB Context: Nuclear hormone receptors exert their transcriptional effects through shared cofactor molecules; thus, defects in such intermediate proteins may be associated with multiple hormone resistance. Microdeletion of small chromosomal segments results in hereditary or sporadic diseases by affecting expression of residing genes.
Objectives: We describe a 7-yr-old boy with partial resistance to glucocorticoids, thyroid hormones, and possibly androgens. He was diagnosed as being in the autism spectrum disorder and had developmental delay and several facial morphological manifestations. We explored genes responsible for multiple hormone resistance of this case.
Results: We found in this patient an approximately 1.1-Mb heterozygous 16p11.2 microdeletion, which included an approximately 500-kb unique deletion along with the common, previously reported approximately 600-kb 16p11.2 microdeletion. The small interfering RNA-based screening revealed that knockdown of ZNF764, which is located in the deleted segment unique to our case, significantly reduced glucocorticoid-, androgen-, and thyroid hormone-induced transcriptional activity of their responsive genes in HeLa cells, whereas its overexpression enhanced their transcriptional activity. The activities of the estrogen and progesterone receptors, cAMP response element-binding protein, and p53 were not affected in these cells. ZNF764 (zinc finger protein 764) expression was reduced in the patient's peripheral blood mononuclear cells, whereas exogenously supplemented ZNF764 recovered responsiveness to glucocorticoids in the patient's Epstein-Barr virus-transformed lymphocytes. The effect of ZNF764 on the glucocorticoid receptor transcriptional activity was mediated through cooperation with a general nuclear hormone receptor coactivator, transcriptional intermediary factor 1.
Conclusions: ZNF764 haploinsufficiency caused by microdeletion may be responsible for the partial multiple hormone resistance observed in our patient. ZNF764 appears to be involved in glucocorticoid, androgen, and thyroid hormone action. (J Clin Endocrinol Metab 97: E1557-E1566, 2012)
C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Clin Res Ctr,NIH, Bethesda, MD 20892 USA.
[Moraitis, Andreas G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Reprod Endocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Moraitis, Andreas G.; Raygada, Margarita; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Nemery, Robin L.] Joe DiMaggio Childrens Hosp, Dept Pediat Endocrinol, Hollywood, FL 33021 USA.
RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Clin Res Ctr,NIH, Bldg 10,Room 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM kinot@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This study was funded by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 29
TC 6
Z9 6
U1 0
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2012
VL 97
IS 8
BP E1557
EP E1566
DI 10.1210/jc.2011-3493
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 987ZI
UT WOS:000307457400026
PM 22577170
ER
PT J
AU Subar, AF
Kirkpatrick, SI
Mittl, B
Zimmerman, TP
Thompson, FE
Bingley, C
Willis, G
Islam, NG
Baranowski, T
McNutt, S
Potischman, N
AF Subar, Amy F.
Kirkpatrick, Sharon I.
Mittl, Beth
Zimmerman, Thea Palmer
Thompson, Frances E.
Bingley, Christopher
Willis, Gordon
Islam, Noemi G.
Baranowski, Tom
McNutt, Suzanne
Potischman, Nancy
TI The Automated Self-Administered 24-Hour Dietary Recall (ASA24): A
Resource for Researchers, Clinicians, and Educators from the National
Cancer Institute
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE 24-hour dietary recall; Dietary assessment
ID BIOMARKER; ACCURACY
C1 [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA.
[Mittl, Beth; Bingley, Christopher] WESTAT Corp, Rockville, MD 20850 USA.
[Zimmerman, Thea Palmer] WESTAT Corp, Cleveland, OH USA.
[Islam, Noemi G.; Baranowski, Tom] USDA ARS, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX USA.
[McNutt, Suzanne] WESTAT Corp, Salt Lake City, UT USA.
RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA.
EM subara@mail.nih.gov
OI Kirkpatrick, Sharon/0000-0001-9896-5975; Baranowski,
Tom/0000-0002-0653-2222
FU National Institutes of Health Institutes and Offices [ASA24]; National
Cancer Institute; National Heart, Lung, and Blood Institute; National
Institute for Child Health and Human Development; National Institute for
Diabetes and Digestive and Kidney Diseases; Office of Dietary
Supplements
FX National Institutes of Health Institutes and Offices providing contract
funding for ASA24: National Cancer Institute, National Heart, Lung, and
Blood Institute, National Institute for Child Health and Human
Development, National Institute for Diabetes and Digestive and Kidney
Diseases, and Office of Dietary Supplements.
NR 12
TC 91
Z9 91
U1 1
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD AUG
PY 2012
VL 112
IS 8
BP 1134
EP 1137
DI 10.1016/j.jand.2012.04.016
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 986CJ
UT WOS:000307318100004
PM 22704899
ER
PT J
AU Miller, DL
O'Grady, NP
AF Miller, Donald L.
O'Grady, Naomi P.
TI Guidelines for the Prevention of Intravascular Catheter-related
Infections: Recommendations Relevant to Interventional Radiology for
Venous Catheter Placement and Maintenance
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID BLOOD-STREAM INFECTIONS; RANDOMIZED CONTROLLED-TRIAL;
INTENSIVE-CARE-UNIT; COAGULASE-NEGATIVE STAPHYLOCOCCI; PULMONARY-ARTERY
CATHETERS; DOUBLE-BLIND TRIAL; TUNNELED INFUSION CATHETERS; LUMEN
SUBCLAVIAN CATHETERS; ANTIBIOTIC-LOCK TECHNIQUE; CRITICALLY-ILL PATIENTS
C1 [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[O'Grady, Naomi P.] NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Miller, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 66,Room 4553,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM donald.miller@fda.hhs.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 130
TC 22
Z9 34
U1 3
U2 22
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 AUG
PY 2012
VL 23
IS 8
BP 997
EP 1006
DI 10.1016/j.jvir.2012.04.023
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 980AI
UT WOS:000306865600003
PM 22840801
ER
PT J
AU Druz, A
Betenbaugh, M
Shiloach, J
AF Druz, Aliaksandr
Betenbaugh, Michael
Shiloach, Joseph
TI Glucose depletion activates mmu-miR-466h-5p expression through oxidative
stress and inhibition of histone deacetylation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DEPRIVATION-INDUCED CYTOTOXICITY; HUMAN LUNG CANCERS; HUMAN TUMOR-CELLS;
NF-KAPPA-B; GENE-EXPRESSION; CIRCULATING MICRORNAS; DOWN-REGULATION;
ACETYLATION; APOPTOSIS; DISEASE
AB MicroRNAs (miRNAs) are involved in the regulation of multiple cellular processes. Changes of miRNA expression have been linked to the development of various diseases including cancer, but the molecular events leading to these changes at different physiological conditions are not well characterized. Here we examined the intracellular events responsible for the miR-466h-5p activation in mouse cells exposed to glucose deprivation. MiR-466h-5p is a member of the miR-297-669 cluster located in intron 10 of Sfmbt2 gene on mouse chromosome 2 and has a pro-apoptotic role. We showed that the time-dependant activation of miR-466h-5p, miR-669c and the Sfmbt2 gene followed the inhibition of histone deacetylation caused by glucose deprivation-induced oxidative stress. This oxidative stress causes the accumulation of reactive oxygen species (ROS) and depletion of reduced glutathione (GSH) that together inhibited histone deacetylases (HDACs) activity, reduced protein levels of HDAC2 and increased acetylation in miR-466h-5p promoter region, which led to the activation of this miRNA. Based on this study and previous work, we suggest a possible role of miR-466h-5p (and miR 297-669 cluster) in the cells during toxic metabolites accumulation. Improved characterization of the molecular events that lead to the activation of miR-466h-5p may provide a better understanding of the relation between cellular environment and miRNA activation.
C1 [Druz, Aliaksandr; Shiloach, Joseph] NIDDKD, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Druz, Aliaksandr; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
RP Shiloach, J (reprint author), NIDDKD, Biotechnol Core Lab, NIH, Bldg 14A, Bethesda, MD 20892 USA.
EM yossi@nih.gov
RI Betenbaugh, Michael J./A-3252-2010
OI Betenbaugh, Michael J./0000-0002-6336-4659
FU Intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health
FX Funding for open access charge: Intramural program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.
NR 47
TC 27
Z9 29
U1 0
U2 6
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 AUG
PY 2012
VL 40
IS 15
BP 7291
EP 7302
DI 10.1093/nar/gks452
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600030
PM 22638581
ER
PT J
AU Wang, J
Cao, HC
You, CJ
Yuan, BF
Bahde, R
Gupta, S
Nishigori, C
Niedernhofer, LJ
Brooks, PJ
Wang, YS
AF Wang, Jin
Cao, Huachuan
You, Changjun
Yuan, Bifeng
Bahde, Ralf
Gupta, Sanjeev
Nishigori, Chikako
Niedernhofer, Laura J.
Brooks, Philip J.
Wang, Yinsheng
TI Endogenous formation and repair of oxidatively induced G[8-5 m]T
intrastrand cross-link lesion
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; DNA-BASE DAMAGE; RNA-POLYMERASE-II;
XERODERMA-PIGMENTOSUM; GUANINE-THYMINE; UVRABC NUCLEASE;
WILSONS-DISEASE; INDEPENDENT GENERATION; HEREDITARY HEPATITIS;
MAMMALIAN-CELLS
AB Exposure to reactive oxygen species (ROS) can give rise to the formation of various DNA damage products. Among them, d(G[8-5m]T) can be induced in isolated DNA treated with Fenton reagents and in cultured human cells exposed to gamma-rays, d(G[8-5m]T) can be recognized and incised by purified Escherichia coli UvrABC nuclease. However, it remains unexplored whether d(G[8-5 m]T) accumulates in mammalian tissues and whether it is a substrate for nucleotide excision repair (NER) in vivo. Here, we found that d(G[8-5 m]T) could be detected in DNA isolated from tissues of healthy humans and animals, and elevated endogenous ROS generation enhanced the accumulation of this lesion in tissues of a rat model of Wilson's disease. Additionally, XPA-deficient human brain and mouse liver as well as various types of tissues of ERCC1-deficient mice contained higher levels of d(G[8-5 m]T) but not ROS-induced single-nucleobase lesions than the corresponding normal controls. Together, our studies established that d(G[8-5 m]T) can be induced endogenously in mammalian tissues and constitutes a substrate for NER in vivo.
C1 [Wang, Jin; Cao, Huachuan; You, Changjun; Yuan, Bifeng; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
[Bahde, Ralf; Gupta, Sanjeev] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Ctr Diabet,Inst Clin & Translat Res,Dept Med, Canc Ctr,Ruth L & David S Gottesman Inst Stem Cel, Bronx, NY 10461 USA.
[Bahde, Ralf; Gupta, Sanjeev] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Ctr Diabet,Inst Clin & Translat Res,Dept Pathol, Canc Ctr,Ruth L & David S Gottesman Inst Stem Cel, Bronx, NY 10461 USA.
[Nishigori, Chikako] Kobe Univ, Grad Sch Med, Div Dermatol, Kobe, Hyogo 6500017, Japan.
[Niedernhofer, Laura J.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
[Brooks, Philip J.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
RP Wang, YS (reprint author), Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
EM yinsheng.wang@ucr.edu
RI Yuan, Bi-Feng/K-5803-2013
OI Yuan, Bi-Feng/0000-0001-5223-4659
FU National Institutes of Health [R01 CA101864, R01 ES016114, R01 DK071111,
R01 DK088561, P30 DK41296]; NIH [R01 CA101864]; [P30CA047904]
FX National Institutes of Health [R01 CA101864 to Y.W.; R01 ES016114 to
L.J.N.; R01 DK071111, R01 DK088561 and P30 DK41296 to S. G.]. This
project used the UPCI Transgenic Animal Facility and was supported in
part by award [P30CA047904]. Funding for open access charge: NIH [R01
CA101864].
NR 60
TC 24
Z9 24
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 AUG
PY 2012
VL 40
IS 15
BP 7368
EP 7374
DI 10.1093/nar/gks357
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600036
PM 22581771
ER
PT J
AU Chorley, BN
Campbell, MR
Wang, XT
Karaca, M
Sambandan, D
Bangura, F
Xue, P
Pi, JB
Kleeberger, SR
Bell, DA
AF Chorley, Brian N.
Campbell, Michelle R.
Wang, Xuting
Karaca, Mehmet
Sambandan, Deepa
Bangura, Fatu
Xue, Peng
Pi, Jingbo
Kleeberger, Steven R.
Bell, Douglas A.
TI Identification of novel NRF2-regulated genes by ChIP-Seq: influence on
retinoid X receptor alpha
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; DIET-INDUCED
OBESITY; CELL LUNG-CANCER; OXIDATIVE STRESS; OLIGONUCLEOTIDE MICROARRAY;
CONSENSUS SEQUENCE; C57BL/6J MICE; SUBUNIT GENE; PPAR-GAMMA
AB Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to deoxyribonucleic acid-regulatory sequences near stress-responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin immunoprecipitation (ChIP)-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two-thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRA has implications for response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells' SFN treatment affected Rxra expression early in adipogenesis, and knockdown of Nrf2-delayed Rxra expression, both leading to impaired adipogenesis.
C1 [Chorley, Brian N.; Campbell, Michelle R.; Wang, Xuting; Karaca, Mehmet; Sambandan, Deepa; Bangura, Fatu; Bell, Douglas A.] NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Xue, Peng; Pi, Jingbo] NIEHS, Hamner Inst, NIH, Res Triangle Pk, NC 27709 USA.
[Kleeberger, Steven R.] NIEHS, Environm Genet Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Bell, DA (reprint author), NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bell1@niehs.nih.gov
RI xue, peng/K-4159-2015;
OI Wang, Xuting/0000-0001-6781-8008
FU The Intramural Research Program of the National Institute of
Environmental Health Sciences; National Institutes of Health
[ZO1-ES-100475-M-0001, ES065079-15, ES016005]; Laboratory of Molecular
Genetics National Institute of Environmental Health Sciences
FX The Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health
[ZO1-ES-100475-M-0001 and ES065079-15 to D. A. B. and ES016005 to J.P.].
Funding for open access charge: Laboratory of Molecular Genetics
National Institute of Environmental Health Sciences.
NR 112
TC 123
Z9 126
U1 9
U2 38
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 AUG
PY 2012
VL 40
IS 15
BP 7416
EP 7429
DI 10.1093/nar/gks409
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600041
PM 22581777
ER
PT J
AU Gosavi, RA
Moon, AF
Kunkel, TA
Pedersen, LC
Bebenek, K
AF Gosavi, Rajendrakumar A.
Moon, Andrea F.
Kunkel, Thomas A.
Pedersen, Lars C.
Bebenek, Katarzyna
TI The catalytic cycle for ribonucleotide incorporation by human DNA Pol
lambda
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID POLYMERASE-BETA; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURES; MU;
DISCRIMINATION; INSERTION; EXCISION; RESIDUE
AB Although most DNA polymerases discriminate against ribonucleotide triphosphaets (rNTPs) during DNA synthesis, recent studies have shown that large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome. Here, we investigate how a DNA polymerase can stably incorporate an rNTP. The X-ray crystal structure of a variant of human DNA polymerase lambda reveals that the rNTP occupies the nucleotide binding pocket without distortion of the active site, despite an unfavorable interaction between the 2'-O and Tyr505 backbone carbonyl. This indicates an energetically unstable binding state for the rNTP, stabilized by additional protein-nucleotide interactions. Supporting this idea is the 200-fold lower catalytic efficiency for rNTP relative to deoxyribonucleotide triphosphate (dNTP) incorporation, reflecting a higher apparent Km value for the rNTP. Furthermore, distortion observed in the structure of the post-catalytic product complex suggests that once the bond between the alpha-and beta-phosphates of the rNTP is broken, the unfavorable binding state of the ribonucleotide cannot be maintained. Finally, structural and biochemical evaluation of dNTP insertion onto an ribonucleotide monophosphate (rNMP)terminated primer indicates that a primer-terminal rNMP does not impede extension. The results are relevant to how ribonucleotides are incorporated into DNA in vivo, during replication and during repair, perhaps especially in non-proliferating cells when rNTP: dNTP ratios are high.
C1 [Gosavi, Rajendrakumar A.; Moon, Andrea F.; Kunkel, Thomas A.; Pedersen, Lars C.; Bebenek, Katarzyna] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kunkel, Thomas A.; Bebenek, Katarzyna] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Bebenek, K (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bebenek@niehs.nih.gov
FU The Division of Intramural Research of the National Institutes of
Health, National Institute of Environmental Health Sciences [Z01
ES065070, Z01 ES102645]; US Department of Energy, Office of Science,
Office of Basic Energy Sciences [W-31-109-Eng-38]; Division of
Intramural Research of the National Institutes of Health, National
Institute of Environmental Health Sciences Project [Z01 ES065070]
FX The Division of Intramural Research of the National Institutes of
Health, National Institute of Environmental Health Sciences [Project Z01
ES065070 to T. A. K. and Project Z01 ES102645 to L. C. P. in parts]. Use
of the Advanced Photon Source was supported by the US Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
contract no. W-31-109-Eng-38. Funding for open access charge: Division
of Intramural Research of the National Institutes of Health, National
Institute of Environmental Health Sciences Project [Z01 ES065070 to
T.A.K.].
NR 27
TC 18
Z9 18
U1 0
U2 6
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 AUG
PY 2012
VL 40
IS 15
BP 7518
EP 7527
DI 10.1093/nar/gks413
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600049
PM 22584622
ER
PT J
AU Mazza, D
Abernathy, A
Golob, N
Morisaki, T
McNally, JG
AF Mazza, Davide
Abernathy, Alice
Golob, Nicole
Morisaki, Tatsuya
McNally, James G.
TI A benchmark for chromatin binding measurements in live cells
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-II; FLUORESCENCE CORRELATION SPECTROSCOPY; IN-VIVO
BINDING; LIVING CELLS; DNA-BINDING; GLUCOCORTICOID-RECEPTOR; DIFFUSION
KINETICS; FACTOR DYNAMICS; RAPID EXCHANGE; TRANSCRIPTION
AB Live-cell measurement of protein binding to chromatin allows probing cellular biochemistry in physiological conditions, which are difficult to mimic in vitro. However, different studies have yielded widely discrepant predictions, and so it remains uncertain how to make the measurements accurately. To establish a benchmark we measured binding of the transcription factor p53 to chromatin by three approaches: fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS) and single-molecule tracking (SMT). Using new procedures to analyze the SMT data and to guide the FRAP and FCS analysis, we show how all three approaches yield similar estimates for both the fraction of p53 molecules bound to chromatin (only about 20%) and the residence time of these bound molecules (similar to 1.8 s). We also apply these procedures to mutants in p53 chromatin binding. Our results support the model that p53 locates specific sites by first binding at sequence-independent sites.
C1 [Mazza, Davide; Abernathy, Alice; Golob, Nicole; Morisaki, Tatsuya; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Mazza, Davide] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
[Mazza, Davide] Osped San Raffaele, Ist Sci, Ctr Imaging Sperimentale, I-20132 Milan, Italy.
RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM mcnallyj@mail.nih.gov
RI Mazza, Davide/R-5340-2016
OI Mazza, Davide/0000-0003-2776-4142
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; Marie Curie international incoming fellowship
[27432]; NIH intramural program
FX Intramural program of the National Institutes of Health (NIH), National
Cancer Institute, Center for Cancer Research; Marie Curie international
incoming fellowship [27432 to D. M., in part]. Funding for open access
charge: NIH intramural program.
NR 54
TC 63
Z9 64
U1 2
U2 17
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 AUG
PY 2012
VL 40
IS 15
AR e119
DI 10.1093/nar/gks701
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600007
PM 22844090
ER
PT J
AU Untergasser, A
Cutcutache, I
Koressaar, T
Ye, J
Faircloth, BC
Remm, M
Rozen, SG
AF Untergasser, Andreas
Cutcutache, Ioana
Koressaar, Triinu
Ye, Jian
Faircloth, Brant C.
Remm, Maido
Rozen, Steven G.
TI Primer3-new capabilities and interfaces
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID NEAREST-NEIGHBOR THERMODYNAMICS; HIGH-THROUGHPUT PIPELINE; CONSERVED PCR
PRIMERS; DOT-T MISMATCHES; DNA-SEQUENCES; QUANTITATIVE PCR; FLEXIBLE
TOOL; DESIGN; GENOME; SOFTWARE
AB Polymerase chain reaction (PCR) is a basic molecular biology technique with a multiplicity of uses, including deoxyribonucleic acid cloning and sequencing, functional analysis of genes, diagnosis of diseases, genotyping and discovery of genetic variants. Reliable primer design is crucial for successful PCR, and for over a decade, the open-source Primer3 software has been widely used for primer design, often in high-throughput genomics applications. It has also been incorporated into numerous publicly available software packages and web services. During this period, we have greatly expanded Primer3's functionality. In this article, we describe Primer3's current capabilities, emphasizing recent improvements. The most notable enhancements incorporate more accurate thermodynamic models in the primer design process, both to improve melting temperature prediction and to reduce the likelihood that primers will form hairpins or dimers. Additional enhancements include more precise control of primer placement-a change motivated partly by opportunities to use whole-genome sequences to improve primer specificity. We also added features to increase ease of use, including the ability to save and re-use parameter settings and the ability to require that individual primers not be used in more than one primer pair. We have made the core code more modular and provided cleaner programming interfaces to further ease integration with other software. These improvements position Primer3 for continued use with genome-scale data in the decade ahead.
C1 [Cutcutache, Ioana; Rozen, Steven G.] Duke NUS Grad Med Sch, Ctr Computat Biol, Singapore 169857, Singapore.
[Untergasser, Andreas] Heidelberg Univ, DKFZ ZMBH Alliance, Zentrum Mol Biol, D-69120 Heidelberg, Germany.
[Koressaar, Triinu; Remm, Maido] Univ Tartu, Inst Mol & Cell Biol, Dept Bioinformat, EE-51010 Tartu, Estonia.
[Ye, Jian] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Faircloth, Brant C.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
RP Rozen, SG (reprint author), Duke NUS Grad Med Sch, Ctr Computat Biol, Singapore 169857, Singapore.
EM steve.rozen@duke-nus.edu.sg
OI Remm, Maido/0000-0003-3966-8422; Rozen, Steven G./0000-0002-4288-0056;
Faircloth, Brant/0000-0002-1943-0217
FU Singapore Ministry of Health; Singapore Agency for Science, Technology,
and Research; E.U. European Regional Development Fund through the
Estonian Centre of Excellence in Genomics; Estonian Ministry of
Education and Research [SF0180026s09]; National Science Foundation of
the U.S.A. [DEB-1136626]; NIH, National Library of Medicine
FX The Singapore Ministry of Health (to S. G. R.); the Singapore Agency for
Science, Technology, and Research (to S. G. R.); the E.U. European
Regional Development Fund through the Estonian Centre of Excellence in
Genomics (to M. R. and T. K.); the Estonian Ministry of Education and
Research [SF0180026s09 to M. R. and T. K]; National Science Foundation
of the U.S.A. [DEB-1136626 to B. C. F.]; Intramural Research Program of
the NIH, National Library of Medicine (to J.Y.). Funding for open access
charge: The Singapore Ministry of Health (to S. G. R.); the Singapore
Agency for Science, Technology, and Research (to S.G.R.).
NR 49
TC 1267
Z9 1283
U1 39
U2 218
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 AUG
PY 2012
VL 40
IS 15
AR e115
DI 10.1093/nar/gks596
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LN
UT WOS:000308958600003
PM 22730293
ER
PT J
AU Kaphingst, KA
Goodman, M
Pandya, C
Garg, P
Stafford, J
Lachance, C
AF Kaphingst, Kimberly A.
Goodman, Melody
Pandya, Chintan
Garg, Priyanka
Stafford, Jewel
Lachance, Christina
TI Factors affecting frequency of communication about family health history
with family members and doctors in a medically underserved population
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Provider-patient communication; Family history; Health information
seeking
ID COMMON CHRONIC DISEASES; NEWEST VITAL SIGN; INFORMATION-SEEKING;
PRIMARY-CARE; COLORECTAL-CANCER; PREVENTIVE BEHAVIORS; BREAST-CANCER;
RISK; GENETICS; GENDER
AB Objective: Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information.
Methods: 1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors.
Results: Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p = .012) and heart disease (p < .001), seek health information frequently in newspapers (p < .001) and in general (p < .001), and be female (p < .001). Patients who talked frequently with doctors about FHH were more likely to report a family history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p < .001) and in general (p < .001), be female (p < .001), and not have experienced racial discrimination in healthcare (p < .001).
Conclusion: Patients with a family history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions.
Practice implications: Interventions are needed to encourage providers to update patients' family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Kaphingst, Kimberly A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Pandya, Chintan; Garg, Priyanka] SUNY Stony Brook, Grad Program Publ Hlth, Stony Brook, NY 11794 USA.
[Lachance, Christina] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Kaphingst, KA (reprint author), Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, Campus Box 8100,660 S Euclid Ave, St Louis, MO 63110 USA.
EM kaphingstk@wudosis.wustl.edu
RI Goodman, Melody/F-6768-2011
OI Goodman, Melody/0000-0001-8932-624X
FU National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
We would like to thank the Suffolk County Department of Health Services,
the Health Center Administrators, the data collectors, and the patients
who agreed to participate in this study.
NR 60
TC 16
Z9 16
U1 0
U2 7
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 AUG
PY 2012
VL 88
IS 2
BP 291
EP 297
DI 10.1016/j.pec.2011.11.013
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 994EW
UT WOS:000307914700020
PM 22197261
ER
PT J
AU Avery, CL
Sethupathy, P
Buyske, S
He, QC
Lin, DY
Arking, DE
Carty, CL
Duggan, D
Fesinmeyer, MD
Hindorff, LA
Jeff, JM
Klein, L
Patton, KK
Peters, U
Shohet, RV
Sotoodehnia, N
Young, AM
Kooperberg, C
Haiman, CA
Mohlke, KL
Whitsel, EA
North, KE
AF Avery, Christy L.
Sethupathy, Praveen
Buyske, Steven
He, Qianchuan
Lin, Dan-Yu
Arking, Dan E.
Carty, Cara L.
Duggan, David
Fesinmeyer, Megan D.
Hindorff, Lucia A.
Jeff, Janina M.
Klein, Liviu
Patton, Kristen K.
Peters, Ulrike
Shohet, Ralph V.
Sotoodehnia, Nona
Young, Alicia M.
Kooperberg, Charles
Haiman, Christopher A.
Mohlke, Karen L.
Whitsel, Eric A.
North, Kari E.
TI Fine-Mapping and Initial Characterization of QT Interval Loci in African
Americans
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; CARDIAC REPOLARIZATION;
GENETIC-VARIATION; TIME-RELATIONS; HEART-RATE; DURATION; POPULATION;
HERITABILITY; PROLONGATION
AB The QT interval (QT) is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE) studies: the Atherosclerosis Risk in Communities study and Women's Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P <= 1.20x10(-4)): ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P <= 1.37x10(-5)): one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD) patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT across multiple populations, that novel signals exist in African Americans, and that the SNPs identified as strong candidates for functional evaluation implicate gene regulatory dysfunction in QT prolongation.
C1 [Avery, Christy L.; Whitsel, Eric A.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
[Sethupathy, Praveen; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sethupathy, Praveen; Mohlke, Karen L.; North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Buyske, Steven] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[He, Qianchuan; Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Carty, Cara L.; Fesinmeyer, Megan D.; Peters, Ulrike; Young, Alicia M.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA.
[Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Jeff, Janina M.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Klein, Liviu] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Patton, Kristen K.; Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Shohet, Ralph V.] Univ Hawaii, Ctr Cardiovasc Res, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Pasadena, CA USA.
[Haiman, Christopher A.] Univ So Calif, Norris Comprehens Canc Ctr, Pasadena, CA USA.
[Whitsel, Eric A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
EM christy_avery@unc.edu
RI Carty, Cara/B-8683-2013;
OI Buyske, Steven/0000-0001-8539-5416; Patton, Kristen
K./0000-0002-9034-6966
FU National Human Genome Research Institute (NHGRI) [U01HG004803,
U01HG004798, U01HG004802, U01HG004790, U01HG004801]; NHGRI PAGE program
[U01HG004803, U01HG004802, U01HG004790, U01HG004798-01]; NHGRI ARRA;
Johns Hopkins University from NHLBI [N01-HV-48195]; Centers for Disease
Control and Prevention; National Cancer Institute [R37CA54281, R01 CA63,
P01CA33619, U01CA136792, U01CA98758]; 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, N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01HL080295, R01 HL087652]; NIH; U.S. Department of Health and Human
Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institutes of
Health, National Heart, Lung and Blood Institute [N01-HC-95095,
N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134,
N01-HC-05187, N01-HC-45205]; National Center for Research Resources
[M01-RR00425]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; NHLBI [U01 HL65520, U01 HL41642, U01 HL41652, U01
HL41654, U01 HL65521]; National Institutes of Mental Health; NHLBI/NIH
[R00HL098458]; NIDDK/NIH [1K99DK091318-01]; [HL088456]
FX The Population Architecture Using Genomics and Epidemiology (PAGE)
program is funded by the National Human Genome Research Institute
(NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (), U01HG004802
(MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center), and
their respective NHGRI ARRA supplements. The contents of this paper are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Institutes of Health (NIH).
The complete list of PAGE members can be found at
http://www.pagestudy.org. The data and materials included in this report
result from a collaboration between the following studies: The
"Epidemiologic Architecture for Genes Linked to Environment'' (EAGLE) is
funded through the NHGRI PAGE program (U01HG004798-01 and its NHGRI ARRA
supplement). Genotyping services for select NHANES III SNPs presented
here were also provided by the Johns Hopkins University under federal
contract number (N01-HV-48195) from NHLBI. The study participants derive
from the National Health and Nutrition Examination Surveys (NHANES), and
these studies are supported by the Centers for Disease Control and
Prevention. The findings and conclusions in this report are those of the
authors and do not necessarily represent the views of the Centers for
Disease Control and Prevention. The Multiethnic Cohort study (MEC)
characterization of epidemiological architecture is funded through the
NHGRI PAGE program (U01HG004802 and its NHGRI ARRA supplement). The MEC
study is funded through the National Cancer Institute (R37CA54281, R01
CA63, P01CA33619, U01CA136792, and U01CA98758). Funding support for the
"Epidemiology of putative genetic variants: The Women's Health
Initiative'' study is provided through the NHGRI PAGE program
(U01HG004790 and its NHGRI ARRA supplement). The WHI program is funded
by the National Heart, Lung, and Blood Institute; NIH; and U.S.
Department of Health and Human Services through contracts N01WH22110,
24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. The authors thank the WHI investigators
and staff for their dedication and the study participants for making the
program possible. A full listing of WHI investigators can be found at:
http://www.whiscience.org/publications/WHI_investigators_shortlist. pdf.
Funding support for the Genetic Epidemiology of Causal Variants Across
the Life Course (CALiCo) program was provided through the NHGRI PAGE
program (U01HG004803 and its NHGRI ARRA supplement). The following
studies contributed to this manuscript and are funded by the following
agencies: 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, and N01-HC-55022. The Coronary
Artery Risk Development in Young Adults (CARDIA) study is supported by
the following National Institutes of Health, National Heart, Lung and
Blood Institute contracts: N01-HC-95095; N01-HC-48047; N01-HC-48048;
N01-HC-48049; N01-HC-48050; N01-HC-45134; N01-HC-05187; and
N01-HC-45205. The Cardiovascular Health Study (CHS) is supported by
contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01 HC-55222, N01-HC-75150, N01-HC-45133, and grants U01HL080295 and R01
HL087652 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke.; CHS GWAS DNA handling and genotyping was
supported in part by National Center for Research Resources grant
M01-RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center. The Strong Heart Study (SHS) is supported
by NHLBI grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and
U01 HL65521. The opinions expressed in this paper are those of the
author(s) and do not necessarily reflect the views of the Indian Health
Service. Assistance with phenotype harmonization, SNP selection and
annotation, data cleaning, data management, integration and
dissemination, and general study coordination was provided by the PAGE
Coordinating Center (U01HG004801-01 and its NHGRI ARRA supplement). The
National Institutes of Mental Health also contributes to the support for
the Coordinating Center. The PAGE consortium thanks the staff and
participants of all PAGE studies for their important contributions. CLA
was partially supported by NHLBI/NIH grant R00HL098458. PS was funded in
part by NIDDK/NIH K99 grant 1K99DK091318-01. NS acknowledges support
from HL088456. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 9
Z9 9
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2012
VL 8
IS 8
AR e1002870
DI 10.1371/journal.pgen.1002870
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 002JX
UT WOS:000308529300028
PM 22912591
ER
PT J
AU Parker, SCJ
Gartner, J
Cardenas-Navia, I
Wei, XM
Abaan, HO
Ajay, SS
Hansen, NF
Song, LY
Bhanot, UK
Killian, JK
Gindin, Y
Walker, RL
Meltzer, PS
Mullikin, JC
Furey, TS
Crawford, GE
Rosenberg, SA
Samuels, Y
Margulies, EH
AF Parker, Stephen C. J.
Gartner, Jared
Cardenas-Navia, Isabel
Wei, Xiaomu
Abaan, Hatice Ozel
Ajay, Subramanian S.
Hansen, Nancy F.
Song, Lingyun
Bhanot, Umesh K.
Killian, J. Keith
Gindin, Yevgeniy
Walker, Robert L.
Meltzer, Paul S.
Mullikin, James C.
Furey, Terrence S.
Crawford, Gregory E.
Rosenberg, Steven A.
Samuels, Yardena
Margulies, Elliott H.
TI Mutational Signatures of De-Differentiation in Functional Non-Coding
Regions of Melanoma Genomes
SO PLOS GENETICS
LA English
DT Article
ID CHRONIC-PANCREATITIS; PROSTATE-CANCER; SEQUENCE; CHROMATIN; ELEMENTS;
TRANSCRIPTION; METASTASIS; ACTIVATION; CONSTRAINT; ENHANCERS
AB Much emphasis has been placed on the identification, functional characterization, and therapeutic potential of somatic variants in tumor genomes. However, the majority of somatic variants lie outside coding regions and their role in cancer progression remains to be determined. In order to establish a system to test the functional importance of non-coding somatic variants in cancer, we created a low-passage cell culture of a metastatic melanoma tumor sample. As a foundation for interpreting functional assays, we performed whole-genome sequencing and analysis of this cell culture, the metastatic tumor from which it was derived, and the patient-matched normal genomes. When comparing somatic mutations identified in the cell culture and tissue genomes, we observe concordance at the majority of single nucleotide variants, whereas copy number changes are more variable. To understand the functional impact of non-coding somatic variation, we leveraged functional data generated by the ENCODE Project Consortium. We analyzed regulatory regions derived from multiple different cell types and found that melanocyte-specific regions are among the most depleted for somatic mutation accumulation. Significant depletion in other cell types suggests the metastatic melanoma cells de-differentiated to a more basal regulatory state. Experimental identification of genome-wide regulatory sites in two different melanoma samples supports this observation. Together, these results show that mutation accumulation in metastatic melanoma is nonrandom across the genome and that a de-differentiated regulatory architecture is common among different samples. Our findings enable identification of the underlying genetic components of melanoma and define the differences between a tissue-derived tumor sample and the cell culture created from it. Such information helps establish a broader mechanistic understanding of the linkage between non-coding genomic variations and the cellular evolution of cancer.
C1 [Parker, Stephen C. J.; Gartner, Jared; Cardenas-Navia, Isabel; Wei, Xiaomu; Abaan, Hatice Ozel; Ajay, Subramanian S.; Hansen, Nancy F.; Mullikin, James C.; Samuels, Yardena; Margulies, Elliott H.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Song, Lingyun; Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA.
[Bhanot, Umesh K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Killian, J. Keith; Gindin, Yevgeniy; Walker, Robert L.; Meltzer, Paul S.; Rosenberg, Steven A.] NCI, NIH, Bethesda, MD 20892 USA.
[Gindin, Yevgeniy] Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.
[Furey, Terrence S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biol, Dept Genet, Chapel Hill, NC 27599 USA.
[Furey, Terrence S.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
RP Parker, SCJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov; emargulies@illumina.com
OI Bhanot, Umeshkumar/0000-0001-6656-1239; Furey, Terry/0000-0001-5546-9672
FU National Human Genome Research Institute (NHGRI), National Institutes of
Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Human Genome Research Institute (NHGRI), National Institutes of
Health (NIH). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 52
TC 5
Z9 5
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2012
VL 8
IS 8
AR e1002871
DI 10.1371/journal.pgen.1002871
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 002JX
UT WOS:000308529300029
PM 22912592
ER
PT J
AU Szabo, R
Sales, KU
Kosa, P
Shylo, NA
Godiksen, S
Hansen, KK
Friis, S
Gutkind, JS
Vogel, LK
Hummler, E
Camerer, E
Bugge, TH
AF Szabo, Roman
Sales, Katiuchia Uzzun
Kosa, Peter
Shylo, Natalia A.
Godiksen, Sine
Hansen, Karina K.
Friis, Stine
Gutkind, J. Silvio
Vogel, Lotte K.
Hummler, Edith
Camerer, Eric
Bugge, Thomas H.
TI Reduced Prostasin (CAP1/PRSS8) Activity Eliminates HAI-1 and HAI-2
Deficiency-Associated Developmental Defects by Preventing Matriptase
Activation
SO PLOS GENETICS
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; SERINE-PROTEASE MATRIPTASE; NEURAL-TUBE
CLOSURE; EPIDERMAL BARRIER FUNCTION; FUNCTIONAL-CHARACTERIZATION;
PLACENTAL DEVELOPMENT; INHIBITOR-1B HAI-1B; PROTEOLYTIC CASCADE;
IRON-DEFICIENCY; XENOPUS-OOCYTES
AB Loss of either hepatocyte growth factor activator inhibitor (HAI)-1 or -2 is associated with embryonic lethality in mice, which can be rescued by the simultaneous inactivation of the membrane-anchored serine protease, matriptase, thereby demonstrating that a matriptase-dependent proteolytic pathway is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this pathway by generating mice with combined deficiency in either HAI-1 or HAI-2, along with genes encoding developmentally co-expressed candidate matriptase targets, and screening for the rescue of embryonic development. Hypomorphic mutations in Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8), restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos. Inactivation of genes encoding c-Met, protease-activated receptor-2 (PAR-2), or the epithelial sodium channel (ENaC) alpha subunit all failed to rescue embryonic lethality, suggesting that deregulated matriptase-prostasin activity causes developmental failure independent of aberrant c-Met and PAR-2 signaling or impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1 and matriptase double-deficient embryos suggests that the protease may not be critical for focal proteolytic activation of PAR-2 during neural tube closure. Paradoxically, although matriptase auto-activates and is a well-established upstream epidermal activator of prostasin, biochemical analysis of matriptase-and prostasin-deficient placental tissues revealed a requirement of prostasin for conversion of the matriptase zymogen to active matriptase, whereas prostasin zymogen activation was matriptase-independent.
C1 [Szabo, Roman; Sales, Katiuchia Uzzun; Kosa, Peter; Shylo, Natalia A.; Godiksen, Sine; Hansen, Karina K.; Friis, Stine; Gutkind, J. Silvio; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Godiksen, Sine; Vogel, Lotte K.] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen, Denmark.
[Godiksen, Sine] Univ Copenhagen, Fac Sci, Dept Biol, Copenhagen, Denmark.
[Hummler, Edith] Univ Lausanne, Dept Pharmacol & Toxicol, Lausanne, Switzerland.
[Camerer, Eric] Paris Cardiovasc Res Ctr, INSERM, U970, Paris, France.
[Camerer, Eric] Univ Paris 05, Paris, France.
RP Szabo, R (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU NIDCR Intramural Research Program; Augustinus Foundation; Kobmand
Kristian Kjaer og Hustrus Foundation; Kjaer-Foundation; Dagmar Marshalls
Foundation; Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens
Foundation; Grosserer Valdemar Foersom og Hustru Thyra Foersoms
Foundation; Fabrikant Einar Willumsens Mindelegat; Harboe Foundation;
Lundbeck Foundation; Swiss National Science Foundation
[31003A-127147/1]; INSERM Avenir; Marie Curie Actions; French National
Research Agency; Ile-de-France Region
FX The study was supported by the NIDCR Intramural Research Program (THB),
the Augustinus Foundation, Kobmand Kristian Kjaer og Hustrus Foundation,
the Kjaer-Foundation, Dagmar Marshalls Foundation, Snedkermester Sophus
Jacobsen og Hustru Astrid Jacobsens Foundation, Grosserer Valdemar
Foersom og Hustru Thyra Foersoms Foundation, Fabrikant Einar Willumsens
Mindelegat, the Harboe Foundation (SG and LKV), the Lundbeck Foundation
(KKH, SG, and LKV), the Swiss National Science Foundation
31003A-127147/1 (EH), the INSERM Avenir, Marie Curie Actions, the French
National Research Agency, and the Ile-de-France Region (EC). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 69
TC 30
Z9 30
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2012
VL 8
IS 8
AR e1002937
DI 10.1371/journal.pgen.1002937
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 002JX
UT WOS:000308529300076
PM 22952456
ER
PT J
AU Voight, BF
Kang, HM
Ding, J
Palmer, CD
Sidore, C
Chines, PS
Burtt, NP
Fuchsberger, C
Li, YM
Erdmann, J
Frayling, TM
Heid, IM
Jackson, AU
Johnson, T
Kilpelainen, TO
Lindgren, CM
Morris, AP
Prokopenko, I
Randall, JC
Saxena, R
Soranzo, N
Speliotes, EK
Teslovich, TM
Wheeler, E
Maguire, J
Parkin, M
Potter, S
Rayner, NW
Robertson, N
Stirrups, K
Winckler, W
Sanna, S
Mulas, A
Nagaraja, R
Cucca, F
Barroso, I
Deloukas, P
Loos, RJF
Kathiresan, S
Munroe, PB
Newton-Cheh, C
Pfeufer, A
Samani, NJ
Schunkert, H
Hirschhorn, JN
Altshuler, D
McCarthy, MI
Abecasis, GR
Boehnke, M
AF Voight, Benjamin F.
Kang, Hyun Min
Ding, Jun
Palmer, Cameron D.
Sidore, Carlo
Chines, Peter S.
Burtt, Noel P.
Fuchsberger, Christian
Li, Yanming
Erdmann, Jeanette
Frayling, Timothy M.
Heid, Iris M.
Jackson, Anne U.
Johnson, Toby
Kilpelaeinen, Tuomas O.
Lindgren, Cecilia M.
Morris, Andrew P.
Prokopenko, Inga
Randall, Joshua C.
Saxena, Richa
Soranzo, Nicole
Speliotes, Elizabeth K.
Teslovich, Tanya M.
Wheeler, Eleanor
Maguire, Jared
Parkin, Melissa
Potter, Simon
Rayner, N. William
Robertson, Neil
Stirrups, Kathleen
Winckler, Wendy
Sanna, Serena
Mulas, Antonella
Nagaraja, Ramaiah
Cucca, Francesco
Barroso, Ines
Deloukas, Panos
Loos, Ruth J. F.
Kathiresan, Sekar
Munroe, Patricia B.
Newton-Cheh, Christopher
Pfeufer, Arne
Samani, Nilesh J.
Schunkert, Heribert
Hirschhorn, Joel N.
Altshuler, David
McCarthy, Mark I.
Abecasis, Goncalo R.
Boehnke, Michael
TI The Metabochip, a Custom Genotyping Array for Genetic Studies of
Metabolic, Cardiovascular, and Anthropometric Traits
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; QT INTERVAL DURATION;
COMMON VARIANTS; SUSCEPTIBILITY LOCI; HAPLOTYPE MAP; IDENTIFIES 13;
HUMAN HEIGHT; RISK; METAANALYSIS
AB Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.
C1 [Speliotes, Elizabeth K.; Maguire, Jared; Parkin, Melissa; Winckler, Wendy; Kathiresan, Sekar; Newton-Cheh, Christopher; Hirschhorn, Joel N.; Altshuler, David] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Speliotes, Elizabeth K.; Maguire, Jared; Parkin, Melissa; Winckler, Wendy; Kathiresan, Sekar; Newton-Cheh, Christopher; Hirschhorn, Joel N.; Altshuler, David] MIT, Cambridge, MA 02139 USA.
[Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Kang, Hyun Min; Sidore, Carlo; Fuchsberger, Christian; Li, Yanming; Jackson, Anne U.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Ding, Jun; Nagaraja, Ramaiah] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Sidore, Carlo; Sanna, Serena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
[Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Chines, Peter S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Nord Ctr Cardiovasc Res, D-23538 Lubeck, Germany.
[Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Heid, Iris M.] Univ Hosp Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Heid, Iris M.] Inst Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, Barts & London Sch Med, London, England.
[Kilpelaeinen, Tuomas O.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Lindgren, Cecilia M.; Morris, Andrew P.; Prokopenko, Inga; Randall, Joshua C.; Rayner, N. William; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Prokopenko, Inga; Rayner, N. William; Robertson, Neil; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Saxena, Richa; Kathiresan, Sekar; Newton-Cheh, Christopher; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Soranzo, Nicole; Wheeler, Eleanor; Potter, Simon; Rayner, N. William; Stirrups, Kathleen; Barroso, Ines; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge, England.
[Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Addenbrookes Hosp, Inst Metab Sci, Cambridge, England.
[Kathiresan, Sekar; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar; Newton-Cheh, Christopher; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Pfeufer, Arne] Deutsch Forsch Zentrum Gesundheit & Umwelt, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Pfeufer, Arne] EURAC Ctr Biomed, Bolzano, Italy.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Coronary Artery Di, Leicester, Leics, England.
[Hirschhorn, Joel N.; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA.
[Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
RP Voight, BF (reprint author), Broad Inst Harvard, Cambridge, MA 02142 USA.
EM altshuler@molbio.mgh.harvard.edu; mark.mccarthy@drl.ox.ac.uk;
goncalo@umich.edu; boehnke@umich.edu
RI Erdmann, Jeanette/P-7513-2014; Deloukas, Panos/B-2922-2013; Pfeufer,
Arne/B-6634-2013; Ding, Jun/G-3918-2011; Abecasis, Goncalo/B-7840-2010;
Altshuler, David/A-4476-2009; Prokopenko, Inga/H-3241-2014;
OI Erdmann, Jeanette/0000-0002-4486-6231; Soranzo,
Nicole/0000-0003-1095-3852; Wheeler, Eleanor/0000-0002-8616-6444;
Deloukas, Panos/0000-0001-9251-070X; Altshuler,
David/0000-0002-7250-4107; Prokopenko, Inga/0000-0003-1624-7457; Mulas,
Antonella/0000-0002-6856-1483; Sidore, Carlo/0000-0001-7504-7477; sanna,
serena/0000-0002-3768-1749; Fuchsberger, Christian/0000-0002-5918-8947;
Johnson, Toby/0000-0002-5998-3270; Abecasis, Goncalo/0000-0003-1509-1825
FU National Institutes of Health [HG000376, HG005214, HG005581, DK062370,
NO1-AG-1-2109]; Wellcome Trust [098051]; British Heart Foundation;
Leicester NIHR Biomedical Research Unit in Cardiovascular Disease
FX Support from the National Institutes of Health (HG000376, HG005214,
HG005581, DK062370, NO1-AG-1-2109), the Wellcome Trust (098051), the
British Heart Foundation, and the Leicester NIHR Biomedical Research
Unit in Cardiovascular Disease is gratefully acknowledged. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
TC 214
Z9 216
U1 0
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2012
VL 8
IS 8
AR e1002793
DI 10.1371/journal.pgen.1002793
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 002JX
UT WOS:000308529300001
PM 22876189
ER
PT J
AU Reese, EA
Cheon, Y
Ramadan, E
Kim, HW
Chang, L
Rao, JS
Rapoport, SI
Taha, AY
AF Reese, Edmund A.
Cheon, Yewon
Ramadan, Epolia
Kim, Hyung-Wook
Chang, Lisa
Rao, Jagadeesh S.
Rapoport, Stanley I.
Taha, Ameer Y.
TI Gabapentin's minimal action on markers of rat brain arachidonic acid
metabolism agrees with its inefficacy against bipolar disorder
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Gabapentin; Arachidonic acid; Bipolar disorder; Mood stabilizer; Drug
screening
ID PROSTAGLANDIN E-2 CONCENTRATION; LITHIUM MAINTENANCE TREATMENT;
CONTROLLED 18-MONTH TRIAL; DOCOSAHEXAENOIC ACID; ACUTE MANIA;
UNANESTHETIZED RAT; PHOSPHOLIPASE A(2); TREATMENT DECREASES; MICROWAVE
FIXATION; CHRONIC VALPROATE
AB In rats, FDA-approved mood stabilizers used for treating bipolar disorder (BD) selectively downregulate brain markers of the arachidonic acid (AA) cascade, which are upregulated in postmortem BD brain. Phase III clinical trials show that the anticonvulsant gabapentin (GBP) is ineffective in treating BD. We hypothesized that GBP would not alter the rat brain AA cascade. Chronic GBP (10 mg/kg body weight, injected i.p. for 30 days) compared to saline vehicle did not significantly alter brain expression or activity of AA-selective cytosolic phospholipase A(2) (cPLA(2)) IVA or secretory (s)PLA(2) IIA, activity of cyclooxygenase-2, or prostaglandin E-2 or thromboxane B-2 concentrations. Plasma esterified and unesterified AA concentration was unaffected. These results, taken with evidence of an upregulated AA cascade in the BD brain and that approved mood stabilizers downregulate the rat brain AA cascade, support the hypothesis that effective anti-BD drugs act by targeting the brain AA cascade whereas ineffective drugs (such as GBP) do not target this pathway, and suggest that the rat model might be used for screening new anti-BD drugs. Published by Elsevier Ltd.
C1 [Reese, Edmund A.; Cheon, Yewon; Ramadan, Epolia; Kim, Hyung-Wook; Chang, Lisa; Rao, Jagadeesh S.; Rapoport, Stanley I.; Taha, Ameer Y.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Taha, AY (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA.
EM ameer.taha@nih.gov
FU National Institute on Aging, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 53
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD AUG-SEP
PY 2012
VL 87
IS 2-3
BP 71
EP 77
DI 10.1016/j.plefa.2012.06.003
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 004LZ
UT WOS:000308684500004
PM 22841517
ER
PT J
AU Young, KD
Erickson, K
Drevets, WC
AF Young, Kymberly D.
Erickson, Kristine
Drevets, Wayne C.
TI MATCH BETWEEN CUE AND MEMORY VALENCE DURING AUTOBIOGRAPHICAL MEMORY
RECALL IN DEPRESSION
SO PSYCHOLOGICAL REPORTS
LA English
DT Article
ID FACIAL EXPRESSIONS; MAJOR DEPRESSION; SPECIFICITY; DISORDER; RESPONSES;
WOMEN; MOOD; BIAS
AB Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories. The current study goal was to assess whether emotionally valenced cue words led to memories of similar emotional valence and whether this pattern differed between 12 unmedicated MUD and 14 healthy control participants. Both groups recalled autobiographical memories in response to positive, negative, and neutral cue words. Positive and neutral cues prompted recall of positive memories less often in the MDD group than in the controls. MDD participants recalled fewer specific and more categorical memories than controls; however, the proportion of specific memories didn't differ across memory valences. The MDD group had fewer specific memories in response to positive and neutral cues than the controls. These results suggest that the MDD participants may process positive stimuli differently than healthy controls and that their recall of specific autobiographical memories is impaired, regardless of the affective valence of those memories.
C1 [Young, Kymberly D.; Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
[Young, Kymberly D.; Erickson, Kristine; Drevets, Wayne C.] NIMH, NIH, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA.
RP Young, KD (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA.
EM kyoung@laureateinstitute.org
OI Young, Kymberly/0000-0001-5133-2142
FU Intramural NIH HHS; NIMH NIH HHS [Z01-MH002792]
NR 33
TC 7
Z9 7
U1 2
U2 16
PU AMMONS SCIENTIFIC, LTD
PI MISSOULA
PA PO BOX 9229, MISSOULA, MT 59807-9229 USA
SN 0033-2941
J9 PSYCHOL REP
JI Psychol. Rep.
PD AUG
PY 2012
VL 111
IS 1
BP 129
EP 148
DI 10.2466/09.02.15.PRO.111.4.129-148
PG 20
WC Psychology, Multidisciplinary
SC Psychology
GA 010IP
UT WOS:000309088400013
PM 23045855
ER
PT J
AU Balsam, J
Bruck, HA
Kostov, Y
Rasooly, A
AF Balsam, Joshua
Bruck, Hugh Alan
Kostov, Yordan
Rasooly, Avraham
TI Image stacking approach to increase sensitivity of fluorescence
detection using a low cost complementary metal-oxide-semiconductor
(CMOS) webcam
SO SENSORS AND ACTUATORS B-CHEMICAL
LA English
DT Article
DE Webcam; Image stacking; CMOS; CCD; LED; Fluorescence; Fluorometer;
Global health
ID STAPHYLOCOCCAL-ENTEROTOXIN-B; LENSLESS DIGITAL HOLOGRAPHY; ARRAY
BIOSENSOR; CARBON NANOTUBES; SENSOR ARRAY; MOBILE PHONE; SYSTEM; CHIP;
IMMUNOASSAY; MICROSCOPY
AB Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector.
1. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.
2. We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image.
While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images. and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 mu M to 1000 mu M. in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is similar to 1000 mu M, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 mu M, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings. Published by Elsevier B.V.
C1 [Balsam, Joshua; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA.
[Balsam, Joshua; Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA.
[Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA.
[Rasooly, Avraham] NCI, Bethesda, MD 20892 USA.
RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA.
EM rasoolya@mail.nih.gov
FU National Cancer Institute, Cancer Diagnosis Program; FDA's Center for
Devices and Radiological Health, Office of Science and Engineering,
Division of Biology
FX Funded by the National Cancer Institute, Cancer Diagnosis Program and
the FDA's Center for Devices and Radiological Health, Office of Science
and Engineering, Division of Biology.
NR 44
TC 13
Z9 13
U1 3
U2 34
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0925-4005
J9 SENSOR ACTUAT B-CHEM
JI Sens. Actuator B-Chem.
PD AUG-SEP
PY 2012
VL 171
BP 141
EP 147
DI 10.1016/j.snb.2012.02.003
PG 7
WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation
SC Chemistry; Electrochemistry; Instruments & Instrumentation
GA 002XQ
UT WOS:000308572700013
PM 23990697
ER
PT J
AU Kleiner, DE
Berman, D
AF Kleiner, David E.
Berman, David
TI Pathologic Changes in Ipilimumab-Related Hepatitis in Patients with
Metastatic Melanoma
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Ipilimumab; Drug-induced hepatitis; CTLA-4; Immunosuppressive therapy;
Metastatic melanoma
ID T-LYMPHOCYTE ANTIGEN-4; INDUCED LIVER-INJURY; AUTOIMMUNE HEPATITIS;
MEDICAL PROGRESS; PHASE-II; REGRESSION; EFFICACY; ANTIBODY
C1 [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Berman, David] Bristol Myers Squibb Co, Res & Dev Global Clin Res, Princeton, NJ 08543 USA.
RP Kleiner, DE (reprint author), NCI, Pathol Lab, Bldg 10,Room 2B50,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kleinerd@mail.nih.gov; david.berman@bms.com
OI Kleiner, David/0000-0003-3442-4453
FU Bristol-Myers Squibb Co.; US National Institutes of Health (National
Cancer Institute)
FX Editorial and writing assistance was provided by StemScientific, funded
by Bristol-Myers Squibb Co. This research was supported in part by the
Intramural Research Program of the US National Institutes of Health
(National Cancer Institute).
NR 22
TC 17
Z9 17
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD AUG
PY 2012
VL 57
IS 8
BP 2233
EP 2240
DI 10.1007/s10620-012-2140-5
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 980YM
UT WOS:000306930100036
PM 22434096
ER
PT J
AU Wise, A
Parham, F
Axelrad, DA
Guyton, KZ
Portier, C
Zeise, L
Zoeller, RT
Woodruff, TJ
AF Wise, Amber
Parham, Fred
Axelrad, Daniel A.
Guyton, Kathryn Z.
Portier, Christopher
Zeise, Lauren
Zoeller, R. Thomas
Woodruff, Tracey J.
TI Upstream adverse effects in risk assessment: A model of polychlorinated
biphenyls, thyroid hormone disruption and neurological outcomes in
humans
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Environmental chemical exposure; Neurodevelopmental outcomes;
Polychlorinated biphenyls; Quantitative risk assessment; Thyroid hormone
ID MICROSOMAL-ENZYME INDUCERS; IN-UTERO EXPOSURE; CONGENITAL
HYPOTHYROIDISM; PCB EXPOSURE; STIMULATING HORMONE; PREGNANT-WOMEN;
SCHOOL-AGE; NEUROPSYCHOLOGICAL DEVELOPMENT; ORGANOCHLORINE PESTICIDES;
MATERNAL HYPOTHYROXINEMIA
AB Background: Increasing data on early biological changes from chemical exposures requires new interpretation tools to support decision-making.
Objectives: To test the possibility of applying a quantitative approach using human data linking chemical exposures and upstream biological perturbations to overt downstream outcomes.
Methods: Using polychlorinated biphenyl (PCB) exposures and maternal thyroid hormone (TH) perturbations as a case study, we model three relationships: (1) prenatal PCB exposures and TH changes, using free T-4 (FT4); (2) prenatal TH and childhood neurodevelopmental outcomes; and (3) prenatal PCB exposures and childhood neurodevelopmental outcomes (IQ). We surveyed the epidemiological literature; extracted relevant quantitative data; and developed models for each relationship, applying meta-analysis where appropriate.
Results: For relationship 1, a meta-analysis of 3 studies gives a coefficient of -0.27 pg/mL FL4 per In(sum of PCBs) (95% confidence interval [CI] -0.82 to 0.27). For relationship 2, regression coefficients from three studies of maternal FT4 levels and cognitive scores ranged between 0.99 IQ points/(pg/mL FT4) (95% Cl -0.31 to 2.2) and 7.6 points/(pg/mL FT4) (95% Cl 1.2 to 16.3). For relationship 3, a meta-analysis of five studies produces a coefficient of -1.98 IQ points (95% Cl -4.46 to 0.50) per unit increase in In(sum of PCBs). Combining relationships 1 and 2 yields an estimate of -2.0 to 0.27 points of IQ per unit increase in ln(sum of PCBs).
Conclusions: Combining analysis of chemical exposures and early biological perturbations (PCBs and FL4) with analysis of early biological perturbations and downstream overt effects (FT4 and IQ) yields estimates within the range of studies of exposures and overt effects (PCBs and IQ). This is an example approach using upstream biological perturbations for effect prediction. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Wise, Amber; Woodruff, Tracey J.] Univ Calif San Francisco, Program Reprod Hlth & Environm, Dept Obstet Gynecol & Reprod Sci, Oakland, CA 94612 USA.
[Parham, Fred; Portier, Christopher] NIEHS, Res Triangle Pk, NC 27709 USA.
[Axelrad, Daniel A.] US EPA, Off Policy, Washington, DC 20460 USA.
[Guyton, Kathryn Z.] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[Zeise, Lauren] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Woodruff, TJ (reprint author), Univ Calif San Francisco, Program Reprod Hlth & Environm, Dept Obstet Gynecol & Reprod Sci, 330 Broadway St,Suite 1100, Oakland, CA 94612 USA.
EM woodrufft@obgyn.ucsf.edu
RI Portier, Christopher/A-3160-2010
OI Portier, Christopher/0000-0002-0954-0279
FU USEPA [EP08h001138]; NIH, National Institute of Environmental Health
Sciences
FX This research was supported under USEPA contract #EP08h001138 and [in
part] by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences.
NR 85
TC 10
Z9 10
U1 4
U2 27
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD AUG
PY 2012
VL 117
BP 90
EP 99
DI 10.1016/j.envres.2012.05.013
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 994EE
UT WOS:000307912900012
PM 22770859
ER
PT J
AU O'Connor, GM
Al Basatena, NKS
Olavarria, V
MacNamara, A
Vine, A
Ying, Q
Hisada, M
Galvao-Castro, B
Asquith, B
McVicar, DW
AF O'Connor, Geraldine M.
Al Basatena, Nafisa-Katrin Seich
Olavarria, Viviana
MacNamara, Aidan
Vine, Alison
Ying, Qi
Hisada, Michie
Galvao-Castro, Bernardo
Asquith, Becca
McVicar, Daniel W.
TI In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1
retroviral infection
SO HUMAN IMMUNOLOGY
LA English
DT Article
ID VIRUS TYPE-I; NK CELLS; PROVIRAL LOAD; GENERAL-POPULATION; ANDEAN MUMMY;
RECEPTOR; TYPE-1; PROGRESSION; MYELOPATHY; DISEASES
AB While most carriers of human T-cell leukemia virus type 1 (HTLV-1) remain asymptomatic throughout their lifetime, infection is associated with the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact parameters that determine these outcomes are unknown but are believed to include host genetic factors that control the immune response to infection. Host response to fellow retroviridae member HIV is influenced by the expression of members of the Killer Immunoglobulin Receptor (KIR) family including KIR3DS1. In this study we examined the association of KIR3DS1 with the outcome of HTLV-1 infection in three geographically distinct cohorts (Jamaican, Japanese and Brazilian). Despite increased prevalence of KIR3DS1 in the HAM/TSP patients of the Jamaican cohort, we found no evidence for a role of KIR3DS1 in influencing control of proviral load or disease outcome. This suggests that unlike HIV, KIR3DS1-mediated regulation of HTLV-1 infection does not occur, or is ineffective. American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [O'Connor, Geraldine M.; Ying, Qi] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA.
[Al Basatena, Nafisa-Katrin Seich; MacNamara, Aidan; Vine, Alison; Asquith, Becca] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London W2 1PG, England.
[Olavarria, Viviana] Escola Bahiana Med & Saude Publ, Ctr HTLV, Salvador, BA, Brazil.
[Hisada, Michie] Takeda Global Res & Dev Ctr Inc, Deerfield, IL 60015 USA.
[Galvao-Castro, Bernardo] Fundacao Oswaldo Cruz, LASP, CPqGM, Salvador, BA, Brazil.
RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Bldg 560,Rm 31-50, Frederick, MD 21702 USA.
EM oconnorg@mail.nih.gov; nafisa-katrin.seich-al-basatena08@imperial.ac.uk;
vini_olavarria@hotmail.com; aidan.macnamara@gmail.com;
alison.levoguer@bindingsite.co.uk; qiy@mail.nih.gov;
michie.hisada@tgrd.com; bgalvao@bahia.fiocruz.br;
b.asquith@imperial.ac.uk; mcvicard@mail.nih.gov
RI McVicar, Daniel/G-1970-2015;
OI Asquith, Becca/0000-0002-5911-3160; MacNamara, Aidan/0000-0001-5958-2429
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; Wellcome Trust; Brazilian
National Research Council (CNPq); Medical Research Council
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project has been funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. This research was supported in part by funding from
the Wellcome Trust and Medical Research Council. This research was
supported in part by the Brazilian National Research Council (CNPq).
NR 33
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD AUG
PY 2012
VL 73
IS 8
BP 783
EP 787
DI 10.1016/j.humimm.2012.05.006
PG 5
WC Immunology
SC Immunology
GA 991IB
UT WOS:000307693600002
PM 22609443
ER
PT J
AU Maruyama, Y
Ebihara, T
Nishiyama, H
Konyuba, Y
Senda, M
Numaga-Tomita, T
Senda, T
Suga, M
Sato, C
AF Maruyama, Yuusuke
Ebihara, Tatsuhiko
Nishiyama, Hidetoshi
Konyuba, Yuji
Senda, Miki
Numaga-Tomita, Takuro
Senda, Toshiya
Suga, Mitsuo
Sato, Chikara
TI Direct Observation of Protein Microcrystals in Crystallization Buffer by
Atmospheric Scanning Electron Microscopy
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE X-ray crystallography; protein crystal; nano-crystal; crystallization
screening; environmental cell; TAF-I beta; micro-focus X-ray beams;
X-ray free-electron laser; ASEM; ClairScope
ID ATOMIC-FORCE MICROSCOPY; CRYSTAL-GROWTH; CHANNEL; TISSUES; CELLS
AB X-ray crystallography requires high quality crystals above a given size. This requirement not only limits the proteins to be analyzed, but also reduces the speed of the structure determination. Indeed, the tertiary structures of many physiologically important proteins remain elusive because of the so-called "crystallization bottleneck". Once microcrystals have been obtained, crystallization conditions can be optimized to produce bigger and better crystals. However, the identification of microcrystals can be difficult due to the resolution limit of optical microscopy. Electron microscopy has sometimes been utilized instead, with the disadvantage that the microcrystals usually must be observed in vacuum, which precludes the usage for crystal screening. The atmospheric scanning electron microscope (ASEM) allows samples to be observed in solution. Here, we report the use of this instrument in combination with a special thin-membrane dish with a crystallization well. It was possible to observe protein crystals of lysozyme, lipase B and a histone chaperone TAF-I beta in crystallization buffers, without the use of staining procedures. The smallest crystals observed with ASEM were a few mu m in width, and ASEM can be used with non-transparent solutions. Furthermore, the growth of salt crystals could be monitored in the ASEM, and the difference in contrast between salt and protein crystals made it easy to distinguish between these two types of microcrystals. These results indicate that the ASEM could be an important new tool for the screening of protein microcrystals.
C1 [Maruyama, Yuusuke; Ebihara, Tatsuhiko; Sato, Chikara] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki 3058566, Japan.
[Nishiyama, Hidetoshi; Konyuba, Yuji; Suga, Mitsuo] JEOL Ltd, Adv Technol Div, Akishima, Tokyo 1968558, Japan.
[Senda, Miki] Japan Biol Informat Consortium JBIC, Struct Guided Drug Dev Project, JBIC Res Inst, Koto Ku, Tokyo 1350064, Japan.
[Numaga-Tomita, Takuro] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Senda, Toshiya] Natl Inst Adv Ind Sci & Technol, Biomedicinal Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan.
RP Sato, C (reprint author), Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Higashi 1-1-1, Tsukuba, Ibaraki 3058566, Japan.
EM yuusuke-maruyama@aist.go.jp; t.ebihara@aist.go.jp; hinishiy@jeol.co.jp;
ykonyuub@jeol.co.jp; miki-senda@aist.go.jp; tomitat2@niehs.nih.gov;
toshiya-senda@aist.go.jp; msuga@jeol.co.jp; ti-sato@aist.go.jp
RI Sato, Chikara/M-7183-2016
FU Japan Science and Technology Agency (JST); Ministry of Education,
Culture, Sports, Science, and Technology (MEXT); AIST
FX We thank Toshihiko Ogura (AIST) for valuable discussions in the
development of the ClairScope, Y. Watanabe (Yamagata Research Institute
of Technology), and M. Koizumi and K. Ogawa (JEOL Technics Ltd.) for
discussions, S. Manaka for technical support, and S. A. Muller and A.
Kohtz for writing assistance. This work was supported by a Grant-in-Aid
for Scientific Research on Innovative Areas, Structural Basis of
Cell-signaling Complexes Mediating Signal Perception, Transduction and
Responses (to C. S.), by grants from the Strategic Japanese-Swiss
Cooperative Program of the Japan Science and Technology Agency (JST) (to
C. S.), by the Ministry of Education, Culture, Sports, Science, and
Technology (MEXT) grant, and by AIST.
NR 27
TC 10
Z9 11
U1 3
U2 23
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1661-6596
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD AUG
PY 2012
VL 13
IS 8
BP 10553
EP 10567
DI 10.3390/ijms130810553
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA 998MK
UT WOS:000308243400076
PM 22949879
ER
PT J
AU Ramadan, E
Basselin, M
Rao, JS
Chang, LS
Chen, M
Ma, KZ
Rapoport, SI
AF Ramadan, Epolia
Basselin, Mireille
Rao, Jagadeesh S.
Chang, Lisa
Chen, Mei
Ma, Kaizong
Rapoport, Stanley I.
TI Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling
in rat brain: implications for its efficacy in bipolar disorder
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Arachidonic acid; cyclooxygenase; mood stabilizer; NMDA receptor;
phospholipase A(2)
ID GLUTATHIONE-S-TRANSFERASE; DNA-BINDING ACTIVITY; D-ASPARTATE-RECEPTOR;
CYTOSOLIC PHOSPHOLIPASE A(2); CHANNEL-MEDIATED RELEASE; COX-2
MESSENGER-RNA; NF-KAPPA-B; FRONTAL-CORTEX; DOCOSAHEXAENOIC ACID;
UNANESTHETIZED RAT
AB An up-regulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-D-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A(2) (cPLA(2)) to release AA from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signalling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanaesthetized rats that had been treated p.o. daily for 42 d with vehicle or a therapeutically relevant dose of LTG (10 mg/kg. d). Regional brain AA incorporation coefficients k* and rates J(in), and AA signals, were measured using quantitative autoradiography after intravenous [1-C-14] AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and J(in) in widespread regions of the brain, as well as prostaglandin (PG)E-2 and thromboxane B-2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE(2) concentration, and DNA-binding activity of the COX-2 transcription factor, NF-kappa B. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signalling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signalling are up-regulated in the post-mortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade.
C1 [Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh S.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Ramadan, E (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM ramadanir@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX The research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. We
appreciate the editorial assistance of the NIH Fellows Editorial Board
and thank Dr Edmund Reese and Dr Ameer Taha for reading the paper.
NR 90
TC 8
Z9 8
U1 2
U2 7
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD AUG
PY 2012
VL 15
IS 7
BP 931
EP 943
DI 10.1017/S1461145711001003
PG 13
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 984KB
UT WOS:000307187400007
PM 21733229
ER
PT J
AU Wierda, RJ
Kuipers, HF
van Eggermond, MCJA
Benard, A
van Leeuwen, JC
Carluccio, S
Geutskens, SB
Jukema, JW
Marquez, VE
Quax, PHA
van den Elsen, PJ
AF Wierda, Rutger J.
Kuipers, Hedwich F.
van Eggermond, Marja C. J. A.
Benard, Anne
van Leeuwen, Jan C.
Carluccio, Silvia
Geutskens, Sacha B.
Jukema, J. Wouter
Marquez, Victor E.
Quax, Paul H. A.
van den Elsen, Peter J.
TI Epigenetic control of CCR5 transcript levels in immune cells and
modulation by small molecules inhibitors
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE chromatin remodelling; histone modifications; DNA methylation; bivalent
chromatin; poised chromatin; CCR5; T cells; monocytes
ID CLASS-II EXPRESSION; RECEPTOR 5 CCR5; DNA METHYLATION; HISTONE
MODIFICATIONS; MULTIPLE-SCLEROSIS; T-CELLS; IMMUNOLOGICAL SYNAPSE;
DEVELOPMENTAL GENES; CHROMATIN DOMAINS; CANCER-CELLS
AB Previously, we have shown that CCR5 transcription is regulated by CREB-1. However, the ubiquitous pattern of CREB-1 expression suggests the involvement of an additional level of transcriptional control in the cell typespecific expression of CCR5. In this study, we show that epigenetic changes (i.e. DNA methylation and histone modifications) within the context of the CCR5 P1 promoter region correlate with transcript levels of CCR5 in healthy and in malignant CD4+ T lymphocytes as well as in CD14+ monocytes. In normal naive T cells and CD14+ monocytes the CCR5 P1 promoter resembles a bivalent chromatin state, with both repressive and permissive histone methylation and acetylation marks. The CCR5-expressing CD14+ monocytes however show much higher levels of acetylated histone H3 (AcH3) compared to the nonCCR5-expressing naive T cells. Combined with a highly methylated promoter in CD14+ monocytes, this indicates a dominant role for AcH3 in CCR5 transcription. We also show that pharmacological interference in the epigenetic repressive mechanisms that account for the lack of CCR5 transcription in T leukaemic cell lines results in an increase in CREB-1 association with CCR5 P1 chromatin. Furthermore, RNA polymerase II was also recruited into CCR5 P1 chromatin resulting in CCR5 re-expression. Together, these data indicate that epigenetic modifications of DNA, and of histones, contribute to the control of CCR5 transcription in immune effector cells.
C1 [Wierda, Rutger J.; Kuipers, Hedwich F.; van Eggermond, Marja C. J. A.; Benard, Anne; van Leeuwen, Jan C.; Carluccio, Silvia; Geutskens, Sacha B.; van den Elsen, Peter J.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands.
[Kuipers, Hedwich F.; van den Elsen, Peter J.] Vrije Univ Amsterdam, Dept Pathol, Med Ctr, Amsterdam, Netherlands.
[Geutskens, Sacha B.; Quax, Paul H. A.] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2333 ZA Leiden, Netherlands.
[Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2333 ZA Leiden, Netherlands.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Quax, Paul H. A.] Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands.
RP van den Elsen, PJ (reprint author), Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Bldg 1,E3-Q,Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
EM pjvdelsen@lumc.nl
OI Van den Elsen, Peter/0000-0002-5196-0082; Quax, Paul/0000-0002-6853-5760
FU Netherlands Ministry of Economic Affairs; Netherlands Ministry of
Education, Culture and Science; Dutch MS Research Foundation [MS 00-407,
MS 04-543]; Macropa Foundation; Department of Immunohematology and Blood
Transfusion; European Union; NIH, National Cancer Institute, Center for
Cancer Research
FX The authors gratefully acknowledge the financial support of the
Translation of Excellence in Regenerative Medicine (TeRM) Smart Mix
Program of the Netherlands Ministry of Economic Affairs and the
Netherlands Ministry of Education, Culture and Science. This research
was further supported by the Dutch MS Research Foundation (MS 00-407 and
MS 04-543), the Macropa Foundation, the Department of Immunohematology
and Blood Transfusion, The European Union Erasmus Program (to S. C.) and
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (to V. E. M.). We thank Prof. Dr. Jeremy Boss
for the gift of the CREB-1 antibody, Prof. M. Mack for the gift of the
MC-5 antibody and Prof. Dr. W. E. Fibbe for his support.
NR 61
TC 12
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD AUG
PY 2012
VL 16
IS 8
BP 1866
EP 1877
DI 10.1111/j.1582-4934.2011.01482.x
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 980QX
UT WOS:000306909200023
PM 22050776
ER
PT J
AU Harries, LW
Fellows, AD
Pilling, LC
Hernandez, D
Singleton, A
Bandinelli, S
Guralnik, J
Powell, J
Ferrucci, L
Melzer, D
AF Harries, Lorna W.
Fellows, Alexander D.
Pilling, Luke C.
Hernandez, Dena
Singleton, Andrew
Bandinelli, Stefania
Guralnik, Jack
Powell, Jonathan
Ferrucci, Luigi
Melzer, David
TI Advancing age is associated with gene expression changes resembling mTOR
inhibition: Evidence from two human populations
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE Aging; Aging mechanisms; mTOR; Human population
ID CALORIC RESTRICTION; DISEASE; HEALTH; TRANSLATION; DISCOVERY; RAPAMYCIN;
INSULIN; KINASE; BLOOD; MICE
AB Interventions which inhibit TOR activity (including rapamycin and caloric restriction) lead to downstream gene expression changes and increased lifespan in laboratory models. However, the role of mTOR signaling in human aging is unclear.
We tested the expression of mTOR-related transcripts in two independent study cohorts; the InCHIANTI population study of aging and the San Antonio Family Heart Study (SAFHS). Expression of 27/56 (InCHIANTI) and 19/44 (SAFHS) genes were associated with age after correction for multiple testing. 8 genes were robustly associated with age in both cohorts. Genes involved in insulin signaling (PTEN, PI3K, PDK1), ribosomal biogenesis (S6K), lipid metabolism (SREBF1), cellular apoptosis (SGK1), angiogenesis (VEGFB), insulin production and sensitivity (FOXO), cellular stress response (HIF1A) and cytoskeletal remodeling (PKC) were inversely correlated with age, whereas genes relating to inhibition of ribosomal components (4EBP1) and inflammatory mediators (STAT3) were positively associated with age in one or both datasets.
We conclude that the expression of mTOR-related transcripts is associated with advancing age in humans. Changes seen are broadly similar to mTOR inhibition interventions associated with increased lifespan in animals. Work is needed to establish whether these changes are predictive of human longevity and whether further mTOR inhibition would be beneficial in older people. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Harries, Lorna W.; Fellows, Alexander D.] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England.
[Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Guralnik, Jack] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Pilling, Luke/E-4917-2013; Harries, Lorna/D-2241-2014; Singleton,
Andrew/C-3010-2009;
OI Pilling, Luke/0000-0002-3332-8454; Melzer, David/0000-0002-0170-3838
FU Intramural Research Program; National Institute on Aging; U.S. National
Institutes of Health; US National Institute on Aging Intramural Research
Program
FX This study was supported in part by the Intramural Research Program,
National Institute on Aging, and the U.S. National Institutes of Health.
We thank the many people who contributed to the InCHIANTI study,
including all of the anonymous participants. The US National Institute
on Aging Intramural Research Program contributed the array data and
supported this analysis. We also acknowledge the San Antonio Family
Heart Study for the use of their data.
NR 35
TC 26
Z9 28
U1 1
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD AUG
PY 2012
VL 133
IS 8
BP 556
EP 562
DI 10.1016/j.mad.2012.07.003
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 007RH
UT WOS:000308905300005
PM 22813852
ER
PT J
AU Mangerich, A
Veith, S
Popp, O
Fahrer, J
Martello, R
Bohr, VA
Burkle, A
AF Mangerich, Aswin
Veith, Sebastian
Popp, Oliver
Fahrer, Joerg
Martello, Rita
Bohr, Vilhelm A.
Buerkle, Alexander
TI Quantitative analysis of WRN exonuclease activity by isotope dilution
mass spectrometry
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE Werner syndrome; WRN; Exonuclease; Mass spectrometry; Aging; PARP1
ID WERNER-SYNDROME PROTEIN; FUNCTIONAL INTERACTION; DEPENDENT DEGRADATION;
HELICASE ACTIVITY; DNA; LESIONS; COMPLEX; KINASE; ENDS; KU
AB Werner syndrome is a disorder characterized by a premature aging phenotype. The disease is caused by mutations in the WRN gene which encodes a DNA helicase/exonuclease which is involved in multiple aspects of DNA metabolism. Current methods mostly rely on radiometric techniques to assess WRN exonuclease activity. Here we present an alternative, quantitative approach based on non-radioactive isotope dilution mass spectrometry (LC-MS/MS). A oligoduplex substrate mimicking the telomeric sequence was used for method development. Released nucleotides, which correlate with the degree of oligoduplex degradation, were dephosphorylated, purified, and quantified by LC-MS/MS. Heavy-isotope-labeled internal standards were used to account for technical variability. The method was validated in terms of reproducibility, time-course and concentration-dependency of the reaction. As shown in this study, the LC-MS/MS method can assess exonuclease activity of WRN mutants, WRN's substrate and strand specificity, and modulatory effects of WRN interaction partners and posttranslational modifications. Moreover, it can be used to analyze the selectivity and processivity of WRN exonuclease and allows the screening of small molecules for WRN exonuclease inhibitors. Importantly, this approach can easily be adapted to study nucleases other than WRN. This is of general interest, because exonucleases are key players in DNA metabolism and aging mechanisms. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Mangerich, Aswin; Veith, Sebastian; Popp, Oliver; Fahrer, Joerg; Martello, Rita; Buerkle, Alexander] Univ Konstanz, Dept Biol, Mol Toxicol Grp, D-78457 Constance, Germany.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Mangerich, A (reprint author), Univ Konstanz, Dept Biol, Mol Toxicol Grp, D-78457 Constance, Germany.
EM aswin.mangerich@uni-konstanz.de; alexander.buerkle@uni-konstanz.de
FU Deutsche Forschungsgemeinschaft (Research Training Group [RTG] [1331];
Deutsche Forschungsgemeinschaft (Konstanz Research School Chemical
Biology, KoRS-CB); University of Konstanz (Ausschuss fur
Forschungsfragen); RTG [1331]; KoRS-CB; intramural Program of the
National Institute on Aging, National Institutes of Health
FX This work was supported by the Deutsche Forschungsgemeinschaft (Research
Training Group [RTG] 1331 and Konstanz Research School Chemical Biology,
KoRS-CB) and the University of Konstanz (Ausschuss fur
Forschungsfragen). SV is supported by a fellowship of the RTG 1331. OP
and RM were supported by fellowships of the KoRS-CB. The work was
partially supported by the intramural Program of the National Institute
on Aging, National Institutes of Health. We would like to thank Peter C.
Dedon, Erin G. Prestwich, and Koli Taghizadeh from the MIT Center for
Environmental Health Sciences for sharing their expertise in
quantitative mass spectrometry.
NR 24
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD AUG
PY 2012
VL 133
IS 8
BP 575
EP 579
DI 10.1016/j.mad.2012.06.005
PG 5
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 007RH
UT WOS:000308905300007
PM 22766507
ER
PT J
AU Neumann, S
Pope, A
Geras-Raaka, E
Raaka, BM
Bahn, RS
Gershengorn, MC
AF Neumann, Susanne
Pope, Arthur
Geras-Raaka, Elizabeth
Raaka, Bruce M.
Bahn, Rebecca S.
Gershengorn, Marvin C.
TI A Drug-Like Antagonist Inhibits Thyrotropin Receptor-Mediated
Stimulation of cAMP Production in Graves' Orbital Fibroblasts
SO THYROID
LA English
DT Article
ID DISEASE; OPHTHALMOPATHY; ADIPOGENESIS; EXPRESSION; AGONISTS
AB Background: Fibroblasts (FIBs) within the retro-orbital space of patients with Graves' disease (GOFs) express thyrotropin receptors (TSHRs) and are thought to be an orbital target of TSHR-stimulating autoantibodies in Graves' ophthalmopathy (GO). Recently, we developed a low molecular weight, drug-like TSHR antagonist (NCGC00229600) that inhibited TSHR activation in a model cell system overexpressing TSHRs and in normal human thyrocytes expressing endogenous TSHRs. Herein, we test the hypothesis that NCGC00229600 will inhibit activation of TSHRs endogenously expressed in GOFs.
Methods: Three strains of GOFs, previously obtained from patients with GO, were studied as undifferentiated FIBs and after differentiation into adipocytes (ADIPs), and another seven strains were studied only as FIBs. ADIP differentiation was monitored by morphology and measurement of adiponectin mRNA. FIBs and ADIPs were treated with the TSH- or TSHR-stimulating antibody M22 in the absence or presence of NCGC00229600 and TSHR activation was monitored by cAMP production.
Results: FIBs contained few if any lipid vesicles and undetectable levels of adiponectin mRNA, whereas ADIPs exhibited abundant lipid vesicles and levels of adiponectin mRNA more than 250,000 times greater than FIBs; TSHR mRNA levels were 10-fold higher in ADIPs than FIBs. FIBs exhibited higher absolute levels of basal and forskolin-stimulated cAMP production than ADIPs. Consistent with previous findings, TSH stimulated cAMP production in the majority of ADIP strains and less consistently in FIBs. Most importantly, NCGC00229600 reduced both TSH- and M22-stimulated cAMP production in GOFs.
Conclusions: These data confirm previous findings that TSHR activation may cause increased cAMP production in GOFs and show that NCGC00229600 can inhibit TSHR activation in GOFs. These findings suggest that drug-like TSHR antagonists may have a role in treatment of GO.
C1 [Neumann, Susanne; Pope, Arthur; Geras-Raaka, Elizabeth; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Bahn, Rebecca S.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN USA.
RP Gershengorn, MC (reprint author), NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU Intramural Research Program of the NIH [1 Z01 DK011006]; [DK77814]
FX This research was supported by the Intramural Research Program of the
NIH (1 Z01 DK011006) and by DK77814 (to RSB). We thank Bernice Samuels
for her excellent technical assistance.
NR 19
TC 21
Z9 25
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 AUG
PY 2012
VL 22
IS 8
BP 839
EP 843
DI 10.1089/thy.2011.0520
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 984KK
UT WOS:000307188300013
PM 22784331
ER
PT J
AU Sue, M
Akama, T
Kawashima, A
Nakamura, H
Hara, T
Tanigawa, K
Wu, H
Yoshihara, A
Ishido, Y
Hiroi, N
Yoshino, G
Kohn, LD
Ishii, N
Suzuki, K
AF Sue, Mariko
Akama, Takeshi
Kawashima, Akira
Nakamura, Hannah
Hara, Takeshi
Tanigawa, Kazunari
Wu, Huhehasi
Yoshihara, Aya
Ishido, Yuko
Hiroi, Naoki
Yoshino, Gen
Kohn, Leonard D.
Ishii, Norihisa
Suzuki, Koichi
TI Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and
Iodide Uptake in Rat Thyroid Cells in the Absence of TSH
SO THYROID
LA English
DT Article
ID PENDRED-SYNDROME GENE; NA+/I-SYMPORTER; ANTITHYROID DRUGS; FRTL-5 CELLS;
GRAVES-DISEASE; TRANSCRIPTION FACTORS; PROTEIN-LEVELS; APICAL PORTER;
FOLLOW-UP; THYROGLOBULIN
AB Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function.
Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies.
Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH.
Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.
C1 [Suzuki, Koichi] Natl Inst Infect Dis, Leprosy Res Ctr, Dept Mycobacteriol, Lab Mol Diagnost, Tokyo 1890002, Japan.
[Sue, Mariko; Nakamura, Hannah; Yoshihara, Aya; Hiroi, Naoki; Yoshino, Gen] Toho Univ, Sch Med, Div Diabet Metab & Endocrinol, Dept Internal Med Omori, Tokyo, Japan.
[Nakamura, Hannah; Kohn, Leonard D.; Suzuki, Koichi] NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD USA.
[Kohn, Leonard D.] Ohio Univ, Coll Osteopath Med, Edison Biotechnol Inst, Dept Biomed Sci, Athens, OH 45701 USA.
RP Suzuki, K (reprint author), Natl Inst Infect Dis, Leprosy Res Ctr, Dept Mycobacteriol, Lab Mol Diagnost, 4-2-1 Aoba Cho, Tokyo 1890002, Japan.
EM koichis@nih.go.jp
FU Japan Society for the Promotion of Science [15390296, 23801300]
FX This work was supported in part by a Grant-in-Aid for Scientific
Research from the Japan Society for the Promotion of Science (#15390296
and #23801300 to K.S.). The authors wish to thank Dr. I.E. Royaux and A.
Mori for their technical assistance and discussions.
NR 52
TC 2
Z9 2
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD AUG
PY 2012
VL 22
IS 8
BP 844
EP 852
DI 10.1089/thy.2011.0290
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 984KK
UT WOS:000307188300014
PM 22853729
ER
PT J
AU Lehmann, S
Guadagni, F
Moore, H
Ashton, G
Barnes, M
Benson, E
Clements, J
Koppandi, I
Coppola, D
Demiroglu, SY
DeSouza, Y
De Wilde, A
Duker, J
Eliason, J
Glazer, B
Harding, K
Jeon, JP
Kessler, J
Kokkat, T
Nanni, U
Shea, K
Skubitz, A
Somiari, S
Tybring, G
Gunter, E
Betsou, F
AF Lehmann, Sabine
Guadagni, Fiorella
Moore, Helen
Ashton, Garry
Barnes, Michael
Benson, Erica
Clements, Judith
Koppandi, Iren
Coppola, Domenico
Demiroglu, Sara Yasemin
DeSouza, Yvonne
De Wilde, Annemieke
Duker, Jacko
Eliason, James
Glazer, Barbara
Harding, Keith
Jeon, Jae Pil
Kessler, Joseph
Kokkat, Theresa
Nanni, Umberto
Shea, Kathi
Skubitz, Amy
Somiari, Stella
Tybring, Gunnel
Gunter, Elaine
Betsou, Fotini
CA Int Soc Biol Environm Repositories
TI Standard Preanalytical Coding for Biospecimens: Review and
Implementation of the Sample PREanalytical Code (SPREC)
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Article
AB The first version of the Standard PREanalytical Code (SPREC) was developed in 2009 by the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group to facilitate documentation and communication of the most important preanalytical quality parameters of different types of biospecimens used for research. This same Working Group has now updated the SPREC to version 2.0, presented here, so that it contains more options to allow for recent technological developments. Existing elements have been fine tuned. An interface to the Biospecimen Reporting for Improved Study Quality (BRISQ) has been defined, and informatics solutions for SPREC implementation have been developed. A glossary with SPREC-related definitions has also been added.
C1 [Lehmann, Sabine; Betsou, Fotini] Integrated Biobank Luxembourg, L-1210 Luxembourg, Luxembourg.
[Guadagni, Fiorella] IRCCS San Raffaele Pisana, Interinst Multidisciplinary Biobank BioBIM, Rome, Italy.
[Moore, Helen] NCI, OBBR, Bethesda, MD 20892 USA.
[Ashton, Garry] Paterson Inst Canc Res, Manchester Canc Res Ctr Biobank, Manchester M20 9BX, Lancs, England.
[Barnes, Michael] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Benson, Erica; Harding, Keith] Damar Res Scientists, Damar, Fife, Scotland.
[Clements, Judith] Queensland Univ Technol, Australian Prostate Inst Hlth & Biomed Innovat, Kelvin Grove, Australia.
[Koppandi, Iren] Cellular Technol Ltd, Shaker Hts, OH USA.
[Coppola, Domenico] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Demiroglu, Sara Yasemin] Univ Med Ctr Gottingen, Dept Med Informat, Gottingen, Germany.
[DeSouza, Yvonne] Univ Calif San Francisco, UCSF AIDS Specimen Bank, San Francisco, CA 94143 USA.
[De Wilde, Annemieke] UZA, Edegem, Belgium.
[Duker, Jacko] Univ Groningen, UMCG Lifelines, Cohort Study, Groningen, Netherlands.
[Eliason, James] Great Lakes Stem Cell Innovat Ctr, Detroit, MI USA.
[Glazer, Barbara] Quintiles Labs, Marietta, GA USA.
[Jeon, Jae Pil] Korea Natl Inst Hlth, Natl Biobank Korea, Chungbuk, South Korea.
[Kessler, Joseph] PPD Vaccines & Biol Lab, Wayne, PA USA.
[Kokkat, Theresa] Univ Penn, Dept Pathol & Lab Med, CHTN, Philadelphia, PA 19104 USA.
[Nanni, Umberto] Univ Roma La Sapienza, Dipartimento Ingn Informat Automat & Gest, Rome, Italy.
[Shea, Kathi] SeraCare Life Sci, Gaithersburg, MD USA.
[Skubitz, Amy] Univ Minnesota, BioNet, Tissue Procurement Facil, Dept Lab Med & Pathol, Minneapolis, MN USA.
[Somiari, Stella] Windber Res Inst, Windber, PA USA.
[Tybring, Gunnel] Karolinska Inst Biobank, Stockholm, Sweden.
[Gunter, Elaine] Specimen Solut LLC, Tucker, GA USA.
RP Betsou, F (reprint author), Integrated Biobank Luxembourg, 6 Rue Nicolas Ernest Barble, L-1210 Luxembourg, Luxembourg.
EM fay.betsou@ibbl.org
RI Guadagni, Fiorella/J-4432-2013; Nanni, Umberto/F-4967-2012;
OI Guadagni, Fiorella/0000-0003-3652-0457; Nanni,
Umberto/0000-0002-2196-6037; Nussbeck, Sara/0000-0003-1223-6494;
Clements, Judith/0000-0001-6026-1964
FU NIAID NIH HHS [P30 AI027763]
NR 7
TC 29
Z9 29
U1 1
U2 12
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1947-5535
EI 1947-5543
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD AUG
PY 2012
VL 10
IS 4
BP 366
EP 374
DI 10.1089/bio.2012.0012
PG 9
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA 999IW
UT WOS:000308304100008
PM 24849886
ER
PT J
AU Catalfamo, M
Le Saout, C
Lane, HC
AF Catalfamo, Marta
Le Saout, Cecile
Lane, H. Clifford
TI The role of cytokines in the pathogenesis and treatment of HIV infection
SO CYTOKINE & GROWTH FACTOR REVIEWS
LA English
DT Review
DE CD4 and CD8 T cell immune activation; T cell homeostasis; IL-7; Type-I
IFN
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL
THERAPY; TYPE-1 INFECTION; SIV INFECTION; GASTROINTESTINAL-TRACT; IMMUNE
ACTIVATION; I INTERFERON; VIRAL LOAD; B-CELLS
AB HIV immune activation plays an important role in the immunopathogenesis of the disease. The mechanisms driving this immune activation are partially defined and likely are the result of multiple factors. The introduction of combination antiretroviral therapy (cART) has improved the life expectancy of HIV infected individuals, however there is evidence that in the setting of "undetectable" HIV-RNA plasma levels, there is some level of persistent immune activation in these patients. A better understanding of the immune activation pathways should be of value in developing complementary therapies to restore the immune systems of patients with HIV infection. This review discusses the cytokine mediated pathways of immune activation of the CD4 and CD8 T cell pools during HIV infection. Published by Elsevier Ltd.
C1 [Catalfamo, Marta; Le Saout, Cecile; Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Catalfamo, M (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11B07, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 106
TC 23
Z9 23
U1 1
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6101
J9 CYTOKINE GROWTH F R
JI Cytokine Growth Factor Rev.
PD AUG-OCT
PY 2012
VL 23
IS 4-5
SI SI
BP 207
EP 214
DI 10.1016/j.cytogfr.2012.05.007
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 006UJ
UT WOS:000308844300008
PM 22738931
ER
PT J
AU Bround, MJ
Wambolt, R
Asghari, P
Luciani, DS
Taghizadeh, F
Kulpa, J
Boheler, KR
Moore, EDW
Allard, MF
Johnson, JD
AF Bround, M. J.
Wambolt, R.
Asghari, P.
Luciani, D. S.
Taghizadeh, F.
Kulpa, J.
Boheler, K. R.
Moore, E. D. W.
Allard, M. F.
Johnson, J. D.
TI Acute cardiac ryanodine receptor loss-of-function leads to bradycardia,
arrhythmia, heart failure and transcriptional metabolic reprogramming
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 25-29, 2012
CL Munchen, GERMANY
SP European Soc Cardiol (ESC)
C1 [Bround, M. J.; Wambolt, R.; Asghari, P.; Luciani, D. S.; Taghizadeh, F.; Kulpa, J.; Moore, E. D. W.; Allard, M. F.; Johnson, J. D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Boheler, K. R.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2012
VL 33
SU 1
BP 880
EP 880
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 995MO
UT WOS:000308012406324
ER
PT J
AU Gjesdal, O
Yoneyama, K
Mewton, N
Gomes, AS
Hundley, G
Prince, M
Shea, SJ
Liu, K
Bluemke, DA
Lima, JAC
AF Gjesdal, O.
Yoneyama, K.
Mewton, N.
Gomes, A. S.
Hundley, G.
Prince, M.
Shea, S. J.
Liu, K.
Bluemke, D. A.
Lima, J. A. C.
TI Normalized mitral annulus displacement predicts heart failure and
cardiovascular events
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 25-29, 2012
CL Munchen, GERMANY
SP European Soc Cardiol (ESC)
C1 [Gjesdal, O.; Yoneyama, K.; Mewton, N.] Johns Hopkins Univ, Baltimore, MD USA.
[Gomes, A. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hundley, G.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Prince, M.; Shea, S. J.] Columbia Univ, Med Ctr, New York, NY USA.
[Liu, K.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Bluemke, D. A.; Lima, J. A. C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2012
VL 33
SU 1
BP 1019
EP 1019
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 995MO
UT WOS:000308012407286
ER
PT J
AU Mukherjee, S
Dawe, AL
Creamer, R
AF Mukherjee, Suman
Dawe, Angus L.
Creamer, Rebecca
TI Potential role for saccharopine reductase in swainsonine metabolism in
endophytic fungus, Undifilum oxytropis
SO FUNGAL BIOLOGY
LA English
DT Article
DE Gene disruption; Saccharopine reductase; Swainsonine; Undifilum
oxytropis
ID PIPECOLIC ACID; INDOLIZIDINE ALKALOIDS; RHIZOCTONIA-LEGUMINICOLA;
LOCOWEED; BIOSYNTHESIS; IMMUNOMODULATOR; ACCUMULATION; ASTRAGALUS;
SLAFRAMINE; PRECURSORS
AB Locoweed plants in the southwestern United States often harbour a slow-growing endophytic fungus, Undifilum oxytropis (Phylum: Ascomycota; Order: Pleosporales), which produces a toxic alkaloid, swainsonine. Consumption of U. oxytropis by grazing animals induces a neurological disorder called locoism for which the toxic alkaloid swainsonine has been reported to be the causal agent. Little is known about the biosynthetic pathway of swainsonine in endophytic fungi, but previous studies on non-endophytic ascomycetous fungi indicate that pipecolic acid and saccharopine are key intermediates. We have used degenerate primers, Rapid amplification of cDNA ends (RACE)-PCR and inverse PCR to identify the gene sequence of U. oxytropis saccharopine reductase. To investigate the role of this gene product in swainsonine metabolism, we have developed a gene deletion system for this slow-growing endophyte based on our recently established transformation protocol. A strain of U. oxytropis lacking saccharopine reductase had decreased levels of saccharopine and lysine along with increased accumulation of pipecolic acid and swainsonine. Thus, saccharopine reductase influences the accumulation of swainsonine and its precursor, pipecolic acid, in U. oxytropis. (C) 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
C1 [Mukherjee, Suman; Dawe, Angus L.; Creamer, Rebecca] New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA.
[Creamer, Rebecca] New Mexico State Univ, Dept Entomol Plant Pathol & Weed Sci, Las Cruces, NM 88003 USA.
[Dawe, Angus L.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA.
RP Mukherjee, S (reprint author), NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA.
EM suman.mukherjee@nih.gov; dawe@nmsu.edu; creamer@nmsu.edu
FU USDA [59-5428-1-327]; New Mexico State University Agricultural
Experiment Station
FX We thank Deana Baucom, Dr Richard Richins, Dr Soum Sanogo, Dr Swati
Mukherjee, and Dr Omar Holguin at New Mexico State University for
technical assistance and constructive discussion. Funding for this
project was provided by USDA Special grant 59-5428-1-327 and the New
Mexico State University Agricultural Experiment Station.
NR 27
TC 3
Z9 6
U1 0
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-6146
EI 1878-6162
J9 FUNGAL BIOL-UK
JI Fungal Biol.
PD AUG
PY 2012
VL 116
IS 8
BP 902
EP 909
DI 10.1016/j.funbio.2012.05.007
PG 8
WC Mycology
SC Mycology
GA 005EA
UT WOS:000308732100006
PM 22862918
ER
PT J
AU Xu, WP
Neckers, L
AF Xu, Wanping
Neckers, Len
TI The double edge of the HSP90-CDC37 chaperone machinery: opposing
determinants of kinase stability and activity
SO FUTURE ONCOLOGY
LA English
DT Editorial Material
DE CDC37; CHIP; HSP/HSC70; HSP90; LKB1
ID PEUTZ-JEGHERS-SYNDROME; TUMOR-SUPPRESSOR LKB1; SPLICE VARIANT;
ACTIVATION; COMPLEX; PATHWAY
AB Evaluation of: Gaude H, Aznar N, Delay A et al. Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1. Oncogene 31(12), 1582-1591 (2012). The molecular chaperone HSP90, in concert with the co-chaperone CDC37, facilitates the maturation and modulates the activity of a variety of protein kinases. In this article, Gaude and colleagues described the dual activities of the HSP90-CDC37 chaperone machinery in maintaining the stability while inhibiting the activity of LKB1 kinase. LKB1 in complex with HSP90-CDC37 has a longer half-life but is incapable of autophosphorylation, and its kinase activity is increased upon HSP90 inhibition. Dissociation of HSP90 from LKB1 results in its interaction with HSP/HSC70. HSP/HSC70 recruits the ubiquitin ligase CHIP, which ubiquitinates LKB1, leading to its proteasome-mediated degradation. These data emphasize the versatile roles of molecular chaperones associated with LKB1 and warrant future studies to characterize the clinical relevance of these observations.
C1 [Xu, Wanping; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM neckersl@mail.nih.gov
FU Intramural NIH HHS [ZIA SC010074-14, Z01 SC010074-12, ZIA SC010074-15,
Z01 SC010074-13, ZIA BC011032-02, ZIA BC011032-03, Z99 CA999999]; NCI
NIH HHS [Z01 BC011032-01]
NR 15
TC 1
Z9 1
U1 0
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
J9 FUTURE ONCOL
JI Future Oncol.
PD AUG
PY 2012
VL 8
IS 8
BP 939
EP 942
DI 10.2217/FON.12.80
PG 4
WC Oncology
SC Oncology
GA 993MF
UT WOS:000307863100010
PM 22894668
ER
PT J
AU Djamshidian, A
O'Sullivan, SS
Sanotsky, Y
Sharman, S
Matviyenko, Y
Foltynie, T
Michalczuk, R
Aviles-Olmos, I
Fedoryshyn, L
Doherty, KM
Filts, Y
Selikhova, M
Bowden-Jones, H
Joyce, E
Lees, AJ
Averbeck, BB
AF Djamshidian, Atbin
O'Sullivan, Sean S.
Sanotsky, Yanosh
Sharman, Stephen
Matviyenko, Yuriy
Foltynie, Thomas
Michalczuk, Rosanna
Aviles-Olmos, Iciar
Fedoryshyn, Ludmyla
Doherty, Karen M.
Filts, Yuriy
Selikhova, Marianna
Bowden-Jones, Henrietta
Joyce, Eileen
Lees, Andrew J.
Averbeck, Bruno B.
TI Decision making, impulsivity, and addictions: Do Parkinson's disease
patients jump to conclusions?
SO MOVEMENT DISORDERS
LA English
DT Article
DE impulsive compulsive behavior; Parkinson's disease; reflection
impulsivity; pathological gambling; substance abuse; beads task
ID DOPAMINE AGONISTS; CONTROL DISORDERS; COMPULSIVE SPECTRUM; NEURAL
MECHANISMS; RISK-FACTORS; REWARD; CORTEX; PERSONALITY; BEHAVIORS; MEMORY
AB Links between impulsive-compulsive behaviors (ICBs) in treated Parkinson's disease (PD), behavioral addictions, and substance abuse have been postulated, but no direct comparisons have been carried out so far. We directly compared patients with PD with and without ICBs with illicit drug abusers, pathological gamblers, and age-matched healthy controls using the beads task, a test of reflection impulsivity, and a working memory task. We found that all patients with PD made more impulsive and irrational choices than the control group. PD patients who had an ICB showed similar behavior to illicit substance abusers, whereas patients without ICBs more closely resembled pathological gamblers. In contrast, we found no difference in working memory performance within the PD groups. However, PD patients without ICBs remembered distractors significantly less than all other patients during working memory tests. We were able to correctly classify 96% of the PD patients with respect to whether or not they had an ICB by analyzing three trials of the 80/20 loss condition of the beads task with a negative prediction value of 92.3%, and we propose that this task may prove to be a powerful screening tool to detect an ICB in PD. Our results also suggest that intact cortical processing and less distractibility in PD patients without ICBs may protect them from developing behavioral addictions. (c) 2012 Movement Disorder Society
C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen M.; Selikhova, Marianna; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen M.; Selikhova, Marianna; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England.
[Sanotsky, Yanosh; Fedoryshyn, Ludmyla] Lviv Reg Clin Hosp, Dept Neurol, Lvov, Ukraine.
[Foltynie, Thomas; Aviles-Olmos, Iciar; Averbeck, Bruno B.] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, London, England.
[Filts, Yuriy] Lviv Reg Clin Psychiat Hosp, Lvov, Ukraine.
[Matviyenko, Yuriy] Lviv Natl Med Univ, Dept Neurol, Lvov, Ukraine.
[Sharman, Stephen; Michalczuk, Rosanna; Joyce, Eileen] UCL, Dept Neuropsychiat, Inst Neurol, London, England.
[Bowden-Jones, Henrietta] CNWL Natl Problem Gambling Clin, London, England.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
RI O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009;
OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian,
Atbin/0000-0001-7174-6000; Sharman, Steve/0000-0001-9816-7981
FU Intramural Research Program of the National Institutes of Health,
National Institute of Mental Health [NIH0014247562]
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, NIH0014247562, National Institute
of Mental Health.
NR 58
TC 31
Z9 31
U1 4
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG
PY 2012
VL 27
IS 9
BP 1137
EP 1145
DI 10.1002/mds.25105
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 986ZY
UT WOS:000307387400014
PM 22821557
ER
PT J
AU Rosen, CJ
Abrams, SA
Aloia, JF
Brannon, PM
Clinton, SK
Durazo-Arvizu, RA
Gallagher, JC
Gallo, RL
Jones, G
Kovacs, CS
Manson, JE
Mayne, ST
Ross, AC
Shapses, SA
Taylor, CL
AF Rosen, Clifford J.
Abrams, Steven A.
Aloia, John F.
Brannon, Patsy M.
Clinton, Steven K.
Durazo-Arvizu, Ramon A.
Gallagher, J. Christopher
Gallo, Richard L.
Jones, Glenville
Kovacs, Christopher S.
Manson, JoAnn E.
Mayne, Susan T.
Ross, A. Catharine
Shapses, Sue A.
Taylor, Christine L.
TI IOM Committee Members Respond to Endocrine Society Vitamin D Guideline
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB The recent publication of the Endocrine Society clinical practice guideline, "Evaluation, Treatment, and Prevention of Vitamin D Deficiency,[has generated considerable controversy. Although there are some agreements in this new guideline with the Institute of Medicine (IOM) Committee's 2011 "Report on Dietary Reference Intakes for Calcium and Vitamin D,[there are substantial differences between these 2 guidelines. These disagreements on several important issues generate confusion for clinicians, researchers, and the public. In this commentary, members of the IOM committee address a number of conclusions in the Endocrine Society guideline that are not supported by adequate evidence and are in need of reconsideration.
Disagreements of the Committee with The Endocrine Society guideline relate to whether targeted serum 25OHD levels are different for the general and at-risk populations, on how vitamin D deficiency should be defined, and on who constitutes a population at risk versus the general population.
Targeted serum 25OHD levels: The guideline does not provide adequate evidence for the assertion that serum levels of 25OHD at 30 ng/mL or higher would be beneficial for at-risk populations (patients with specific underlying conditions such as osteoporosis, kidney or liver dysfunction, malabsorption syndromes, obesity, and pregnancy) compared with the general population. The guideline conclusion with respect to serum 25OHD levels and calcium absorption was based in large part on a single small study published in 2003 evaluating 34 subjects who did not undergo formal calcium absorption tests. The guideline did not include more appropriate data from trials evaluating more than 1000 subjects who underwent formal calcium absorption tests. The overall data from these larger studies contradict the 2003 study and show that calcium absorption reaches near maximum between serum 25OHD levels of 8 to 20 ng/mL.
Definition of vitamin D deficiency: The guideline mistakenly concludes that vitamin D is beneficial for a large segment of our population only when serum levels are at 30 ng/mL 25OHD and more and that individuals with serum 25OHD levels less than 20 ng/mL are deficient in vitamin D. The assertion that vitamin D deficiency is present for serum levels of 25OHD in the general population that are less than 20 ng/mL is inconsistent with data showing that a serum level of 16 ng/mL is adequate in 50% of the general population. In addressing the question of insufficient levels of vitamin D, the guideline includes a selected subgroup of available data with no explanation for inclusion of these studies and the exclusion of others.
Who constitutes a population at risk versus the general population? The intent of the guideline was to target those with disease and high-risk populations not covered by the IOM report, but in doing so, it inappropriately includes some conditions that are considered to be part of the general population.
The IOM committee believes that a systematic evidence-based approach assessing the evidence for both benefits and risks of supplementation for individuals with underlying health conditions is needed. The current Endocrine Society guideline does not reflect an evidence-based approach and needs to be reexamined.
C1 [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA.
Baylor Coll Med, Houston, TX 77030 USA.
SUNY Stony Brook, Mineola, NY USA.
Winthrop Univ Hosp, Mineola, NY 11501 USA.
Cornell Univ, Ithaca, NY USA.
Ohio State Univ, Columbus, OH 43210 USA.
Loyola Univ Chicago, Maywood, IL USA.
Creighton Univ, Med Ctr, Omaha, NE USA.
Univ Calif San Diego, San Diego, CA 92103 USA.
Queens Univ, Kingston, ON, Canada.
Mem Univ Newfoundland, St John, NF, Canada.
Harvard Univ, Sch Med, Boston, MA USA.
Yale Univ, Sch Publ Hlth, New Haven, CT USA.
Penn State Univ, University Pk, PA 16802 USA.
Rutgers State Univ, New Brunswick, NJ 08903 USA.
NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Rosen, CJ (reprint author), Maine Med Ctr, Res Inst, Scarborough, ME USA.
OI Kovacs, Christopher/0000-0002-5219-9993
NR 0
TC 0
Z9 0
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD AUG
PY 2012
VL 67
IS 8
BP 479
EP 480
DI 10.1097/01.ogx.0000418531.13405.69
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 005LG
UT WOS:000308751300014
ER
PT J
AU Miller, SA
Coelho, SG
Miller, SW
Yamaguchi, Y
Hearing, VJ
Beer, JZ
AF Miller, Sharon A.
Coelho, Sergio G.
Miller, Scott W.
Yamaguchi, Yuji
Hearing, Vincent J.
Beer, Janusz Z.
TI Evidence for a new paradigm for ultraviolet exposure: a universal
schedule that is skin phototype independent
SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE
LA English
DT Article
DE exposure schedule; indoor tanning; skin phototype; ultraviolet
ID DNA-DAMAGE; PIGMENTATION; RADIATION; ERYTHEMA; KINETICS; SPECTRUM;
INTERVAL
AB Background: The Food and Drug Administration has published guidelines for manufacturer-recommended exposure schedules for ultraviolet (UV) tanning, intended to limit acute and delayed damage from UV exposure. These guidelines recommend that exposure schedules be adjusted for skin phototype. However, it has been shown that the dose necessary to produce tanning is similar for phototypes 2-4.
Methods: We observed tanning in phototypes 2 and 3 from repeated UV exposures over a 5-week period. Pigmentation was evaluated visually, instrumentally, and through Fontana-Masson staining of biopsies.
Results: The resultant pigmentation was equal or greater in phototype 3 compared with phototype 2 - both visually and instrumentally - measured on day 31 of the exposure protocol. The amount of melanin measured in biopsies taken 24 h postexposure was also greater in phototype 3 compared with phototype 2.
Conclusion: Published data on tanning in phototypes 4 and 5 support our findings that higher phototypes can develop pigmentation more efficiently than lower phototypes. Therefore, a universal exposure schedule (based on sensitivity of phototype 2) can be used for all phototypes that are expected to engage in indoor tanning. This approach will result in a reduction of the UV burden for skin phototypes 3 and above.
C1 [Miller, Sharon A.; Miller, Scott W.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Coelho, Sergio G.; Yamaguchi, Yuji; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 1114, Silver Spring, MD 20993 USA.
EM sharona.miller@fda.hhs.gov
FU US FDA Office of Women's Health; National Cancer Institute, National
Institute of Health
FX This research was supported by the US FDA Office of Women's Health and
in part by the Intramural Research Program of the National Cancer
Institute, National Institute of Health. The authors wish to express
their sincere appreciation to Dr Katalin S. Korossey for her
dermatological support and numerous valuable suggestions and to Judith
Kniskern, RN, for her excellent handling of the human subjects and
records.
NR 29
TC 2
Z9 2
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0905-4383
J9 PHOTODERMATOL PHOTO
JI Photodermatol. Photoimmunol. Photomed.
PD AUG
PY 2012
VL 28
IS 4
BP 187
EP 195
DI 10.1111/j.1600-0781.2012.00666.x
PG 9
WC Dermatology
SC Dermatology
GA 004ZT
UT WOS:000308720800003
PM 23017171
ER
PT J
AU Salari, R
Wojtowicz, D
Zheng, J
Levens, D
Pilpel, Y
Przytycka, TM
AF Salari, Raheleh
Wojtowicz, Damian
Zheng, Jie
Levens, David
Pilpel, Yitzhak
Przytycka, Teresa M.
TI Teasing Apart Translational and Transcriptional Components of Stochastic
Variations in Eukaryotic Gene Expression
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; SINGLE-CELL; SACCHAROMYCES-CEREVISIAE;
QUANTITATIVE-ANALYSIS; REGULATORY NETWORKS; SECONDARY STRUCTURE;
BIOLOGICAL-SYSTEMS; PROTEIN EXPRESSION; CODON SELECTION; NOISE
AB The intrinsic stochasticity of gene expression leads to cell-to-cell variations, noise, in protein abundance. Several processes, including transcription, translation, and degradation of mRNA and proteins, can contribute to these variations. Recent single cell analyses of gene expression in yeast have uncovered a general trend where expression noise scales with protein abundance. This trend is consistent with a stochastic model of gene expression where mRNA copy number follows the random birth and death process. However, some deviations from this basic trend have also been observed, prompting questions about the contribution of gene-specific features to such deviations. For example, recent studies have pointed to the TATA box as a sequence feature that can influence expression noise by facilitating expression bursts. Transcription-originated noise can be potentially further amplified in translation. Therefore, we asked the question of to what extent sequence features known or postulated to accompany translation efficiency can also be associated with increase in noise strength and, on average, how such increase compares to the amplification associated with the TATA box. Untangling different components of expression noise is highly nontrivial, as they may be gene or gene-module specific. In particular, focusing on codon usage as one of the sequence features associated with efficient translation, we found that ribosomal genes display a different relationship between expression noise and codon usage as compared to other genes. Within nonribosomal genes we found that sequence high codon usage is correlated with increased noise relative to the average noise of proteins with the same abundance. Interestingly, by projecting the data on a theoretical model of gene expression, we found that the amplification of noise strength associated with codon usage is comparable to that of the TATA box, suggesting that the effect of translation on noise in eukaryotic gene expression might be more prominent than previously appreciated.
C1 [Salari, Raheleh; Wojtowicz, Damian; Przytycka, Teresa M.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Wojtowicz, Damian] Univ Warsaw, Inst Informat, Warsaw, Poland.
[Zheng, Jie] Nanyang Technol Univ, Bioinformat Res Ctr BIRC, Sch Comp Engn, Singapore, Singapore.
[Levens, David] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Pilpel, Yitzhak] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
RP Salari, R (reprint author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
EM przytyck@ncbi.nlm.nih.gov
RI Zheng, Jie/C-1356-2011; Levens, David/C-9216-2009
OI Zheng, Jie/0000-0001-6774-9786; Levens, David/0000-0002-7616-922X
FU Intramural Program of National Institutes of Health NLM; NCI; CCR;
Polish Ministry of Science and Higher Education [NN301065236]; European
Research Council; Ben May Foundation; Nanyang Technological University,
Singapore [M4080108.020]
FX The research was supported in part by the Intramural Program of National
Institutes of Health NLM (RS, JZ, DW, TMP) and NCI, CCR (DL), as well as
in part by a grant from the Polish Ministry of Science and Higher
Education (NN301065236) to DW. YP is supported by an "Ideas" grant of
the European Research Council and the Ben May Foundation. JZ was also
supported in part by start-up grant (M4080108.020) at Nanyang
Technological University, Singapore. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 59
TC 11
Z9 11
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD AUG
PY 2012
VL 8
IS 8
AR e1002644
DI 10.1371/journal.pcbi.1002644
PG 7
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 002SA
UT WOS:000308553500030
PM 22956896
ER
PT J
AU Campbell, TB
Smeaton, LM
Kumarasamy, N
Flanigan, T
Klingman, KL
Firnhaber, C
Grinsztejn, B
Hosseinipour, MC
Kumwenda, J
Lalloo, U
Riviere, C
Sanchez, J
Melo, M
Supparatpinyo, K
Tripathy, S
Martinez, AI
Nair, A
Walawander, A
Moran, L
Chen, Y
Snowden, W
Rooney, JF
Uy, J
Schooley, RT
De Gruttola, V
Hakim, JG
AF Campbell, Thomas B.
Smeaton, Laura M.
Kumarasamy, N.
Flanigan, Timothy
Klingman, Karin L.
Firnhaber, Cynthia
Grinsztejn, Beatriz
Hosseinipour, Mina C.
Kumwenda, Johnstone
Lalloo, Umesh
Riviere, Cynthia
Sanchez, Jorge
Melo, Marineide
Supparatpinyo, Khuanchai
Tripathy, Srikanth
Martinez, Ana I.
Nair, Apsara
Walawander, Ann
Moran, Laura
Chen, Yun
Snowden, Wendy
Rooney, James F.
Uy, Jonathan
Schooley, Robert T.
De Gruttola, Victor
Hakim, James Gita
CA PEARLS Study Team ACTG
TI Efficacy and Safety of Three Antiretroviral Regimens for Initial
Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational
Settings
SO PLOS MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS DISEASE; RETROVIRAL-NAIVE PATIENTS; LOW-DOSE
RITONAVIR; ADVERSE EVENTS; BACTERIAL-INFECTION; EFAVIRENZ; THERAPY;
EMTRICITABINE; DIDANOSINE; LAMIVUDINE
AB Background: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.
Methods and Findings: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was <= 1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).
Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.
C1 [Campbell, Thomas B.] Univ Colorado, Sch Med, Dept Med, Div Infect Dis, Aurora, CO 80045 USA.
[Smeaton, Laura M.; Chen, Yun; De Gruttola, Victor] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Kumarasamy, N.] YRG Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India.
[Flanigan, Timothy] Brown Med Sch, Providence, RI USA.
[Klingman, Karin L.; Martinez, Ana I.] NIH, Bethesda, MD 20892 USA.
[Firnhaber, Cynthia] Univ Witwatersrand, Dept Med, Fac Hlth Sci, Clin HIV Res Unit, ZA-2001 Johannesburg, South Africa.
[Grinsztejn, Beatriz] Fiocruz MS, Evandro Chagas Clin Res Inst, BR-21045900 Rio De Janeiro, Brazil.
[Hosseinipour, Mina C.] Kamuzu Cent Hosp, Lilongwe, Malawi.
[Kumwenda, Johnstone] Coll Med, Dept Med, Blantyre, Malawi.
[Lalloo, Umesh] Nelson R Mandela Sch Med, Durban, South Africa.
[Riviere, Cynthia] Inst Nacl Lab & Rech, Port Au Prince, Haiti.
[Sanchez, Jorge] Asociac Civil Impacta Salud & Educ, Lima, Peru.
[Melo, Marineide] Hosp Nossa Senhora da Conceicao GHC, Serv Infectol, Porto Alegre, RS, Brazil.
[Supparatpinyo, Khuanchai] Chiang Mai Univ, Dept Med, Chiang Mai 50000, Thailand.
[Supparatpinyo, Khuanchai] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Tripathy, Srikanth] Natl AIDS Res Inst, Pune, Maharashtra, India.
[Nair, Apsara; Walawander, Ann] Frontier Sci & Technol Res Fdn Inc, Amherst, MA USA.
[Moran, Laura] Social & Sci Syst Inc, Silver Spring, MD USA.
[Snowden, Wendy] GlaxoSmithKline, Res Triangle Pk, NC USA.
[Rooney, James F.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Uy, Jonathan] Bristol Myers Squibb Co, Plainsboro, NJ USA.
[Schooley, Robert T.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Hakim, James Gita] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe.
RP Campbell, TB (reprint author), Univ Colorado, Sch Med, Dept Med, Div Infect Dis, Aurora, CO 80045 USA.
EM thomas.campbell@ucdenver.edu
OI Berendes, Sima/0000-0001-7000-868X
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health [AI68636, AI68634, A1069432, AI069476, AI069518,
AI069426, AI069436, AIO69463, AI069399, AI069401, AI069421, AI069417,
AI069438, AI046376, AI069513, AI38858, AI69450, AI069474, AI069471,
AI27661, AI069495, AI069484, AI47370, A1069472, AI069428, A1069424,
AI069423, AI050410, AI-069439, AI54999, RR024975, A1069467, AI045008,
AI069470, AI069532, AI032782, AI069511, AI069424, AI69419, RR024996,
RR00865, RR024160, RR024156, RR025747, RR00424, RR025780]; Boehringer
Ingelheim; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline
FX The study was funded by the National Institute of Allergy and Infectious
Diseases and the following National Institutes of Health: grants
AI68636, AI68634, A1069432, AI069476, AI069518, AI069426, AI069518,
AI069436, AIO69463, AI069399, AI069401, AI069421, AI069417, AI069438,
AI069438, AI046376, AI069417, AI069513, AI38858, AI069417, AI69450,
AI069474, AI069471, AI27661, AI069495, AI069484, AI47370, A1069472,
AI069428, A1069424, AI069423, AI050410, AI-069439; AI54999, RR024975,
A1069467, AI045008, AI069470, AI069471, AI069532, AI032782, AI069511,
AI069424, AI069471, AI69419, RR024996, RR00865, RR024160, RR024156,
RR025747, RR00424 and RR025780. Employees of the NIAID participated as
study team members and authors of this manuscript. The NIAID provided
recommendations on the study design and approved the final study design,
but had no role in data collection and analysis, decision to publish, or
preparation of the manuscript. The pharmaceutical sponsors (Boehringer
Ingelheim, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline)
provided study drug and Gilead Sciences provided funding to purchase
study drug that was not otherwise available. Bristol Myers Squibb
provided atazanavir, didanosine-EC and efavirenz (with consent of
Merck); Gilead Sciences, Inc. provided emtricitabine, tenofovir-DF,
emtricitabine/tenofovir-DF; GlaxoSmithKline provided lamivudine,
zidovudine and lamivudine/zidovudine; and Boehringer Ingelheim
Pharmaceuticals, Inc. provided nevirapine. Representatives of the
pharmaceutical company sponsors participated as study team members and
authors of this manuscript, but did not participate in data collection,
data analyses or interpretation. Bristol Myers Squibb, Gilead Sciences
Inc., GlaxoSmithKline and Boehringer Ingelheim Pharmaceuticals, Inc. had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 32
TC 63
Z9 63
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD AUG
PY 2012
VL 9
IS 8
AR e1001290
DI 10.1371/journal.pmed.1001290
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA 001XU
UT WOS:000308494600011
PM 22936892
ER
PT J
AU Brady, OJ
Gething, PW
Bhatt, S
Messina, JP
Brownstein, JS
Hoen, AG
Moyes, CL
Farlow, AW
Scott, TW
Hay, SI
AF Brady, Oliver J.
Gething, Peter W.
Bhatt, Samir
Messina, Jane P.
Brownstein, John S.
Hoen, Anne G.
Moyes, Catherine L.
Farlow, Andrew W.
Scott, Thomas W.
Hay, Simon I.
TI Refining the Global Spatial Limits of Dengue Virus Transmission by
Evidence-Based Consensus
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DOMINANT ANOPHELES VECTORS; DISTRIBUTION MAPS; BIONOMIC PRECIS; HUMAN
MALARIA; CHIKUNGUNYA VIRUS; NORTH QUEENSLAND; LATIN-AMERICA;
YELLOW-FEVER; MIDDLE-EAST; DISEASE
AB Background: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status.
Methods/Principal Findings: A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence.
Conclusion: The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.
C1 [Brady, Oliver J.; Gething, Peter W.; Bhatt, Samir; Messina, Jane P.; Moyes, Catherine L.; Farlow, Andrew W.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Brady, Oliver J.] Oxitec Ltd, Abingdon, Oxon, England.
[Brownstein, John S.] Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA.
[Brownstein, John S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Hoen, Anne G.] Dartmouth Coll, Dept Community & Family Med, Hanover, NH 03755 USA.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Scott, Thomas W.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Brady, OJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England.
EM oliver.brady@zoo.ox.ac.uk; simon.i.hay@gmail.com
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Gething, Peter/0000-0001-6759-5449;
Brady, Oliver/0000-0002-3235-2129; Moyes, Catherine/0000-0002-8028-4079
FU BBSRC; University of Oxford; Oxitec Ltd, Abingdon, U.K.; Wellcome Trust
[079091]; Biomedical Resources Grant from the Wellcome Trust [091835];
National Library of Medicine [R01 LM010812, G08 LM009776]; International
Research Consortium on Dengue Risk Assessment Management and
Surveillance (IDAMS, European Commission 7th Framework Programme)
[21803]; RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health
FX OJB is funded by a BBSRC Industrial CASE studentship award held by the
University of Oxford and Oxitec Ltd, Abingdon, U.K. SIH is funded by a
Senior Research Fellowship from the Wellcome Trust (#079091), which also
supports PWG. CLM is funded by a Biomedical Resources Grant from the
Wellcome Trust (#091835). JSB is funded by National Library of Medicine
grants R01 LM010812 and G08 LM009776. JM, AF, and SIH received funding
from and with OJB, PWG, and SB acknowledge the contribution of the
International Research Consortium on Dengue Risk Assessment Management
and Surveillance (IDAMS, European Commission 7th Framework Programme
(#21803) (http://www.idams.eu). SIH and TWS also acknowledge support
from the RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health (http://www.fic.nih.gov). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 66
TC 202
Z9 210
U1 4
U2 65
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2012
VL 6
IS 8
AR e1760
DI 10.1371/journal.pntd.0001760
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 001YS
UT WOS:000308497100009
PM 22880140
ER
PT J
AU Vazquez-Prokopec, GM
Spillmann, C
Zaidenberg, M
Gurtler, RE
Kitron, U
AF Vazquez-Prokopec, Gonzalo M.
Spillmann, Cynthia
Zaidenberg, Mario
Guertler, Ricardo E.
Kitron, Uriel
TI Spatial Heterogeneity and Risk Maps of Community Infestation by Triatoma
infestans in Rural Northwestern Argentina
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CHAGAS-DISEASE VECTOR; TRYPANOSOMA-CRUZI INFECTION; GRAN-CHACO;
INSECTICIDE RESISTANCE; PERIDOMESTIC POPULATIONS; PYRETHROID
INSECTICIDES; HEMIPTERA REDUVIIDAE; CONTROL STRATEGIES; COMPARATIVE
TRIAL; LA-RIOJA
AB Background: Fifty years of residual insecticide spraying to control Triatoma infestans in the Gran Chaco region of northern Argentina, Paraguay and Bolivia shows that vertically coordinated interventions aiming at full coverage have limited effects and are unsustainable. We quantified the spatial distribution of T. infestans domestic infestation at the district level, identified environmental factors associated with high infestation and then explored the usefulness of risk maps for the spatial stratification of interventions.
Methods and Findings: We performed spatial analyses of house infestation data collected by the National Chagas Service in Moreno Department, northern Argentina (1999-2002). Clusters of high domestic infestation occurred in the southwestern extreme of the district. A multi-model selection approach showed that domestic infestation clustered in areas of low elevation, with few farmlands, high density of rural houses, high mean maximum land surface temperature, large NDVI, and high percentage of degraded and deforested lands. The best model classified 98.4% of the communities in the training dataset (sensitivity, 93.3%; specificity, 95.4%). The risk map evidenced that the high-risk area only encompassed 16% of the district. By building a network-based transportation model we assessed the operational costs of spatially contiguous and spatially targeted interventions. Targeting clusters of high infestation would have reached similar to 80% of all communities slated for full-coverage insecticide spraying, reducing in half the total time and economic cost incurred by a spatially contiguous strategy.
Conclusions and Significance: In disperse rural areas where control programs can accomplish limited coverage, consideration of infestation hot spots can contribute to the design and execution of cost-effective interventions against Chagas disease vectors. If field validated, targeted vertical control in high risk areas and horizontal control in medium to low risk areas may provide both a logistically and economically feasible alternative to blanket vertical insecticide spraying when resources are limited.
C1 [Vazquez-Prokopec, Gonzalo M.; Guertler, Ricardo E.] Univ Buenos Aires, Lab Ecoepidemiol, Buenos Aires, DF, Argentina.
[Vazquez-Prokopec, Gonzalo M.; Kitron, Uriel] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA.
[Vazquez-Prokopec, Gonzalo M.; Kitron, Uriel] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Spillmann, Cynthia; Zaidenberg, Mario] Minist Salud Nac, Coordinac Nacl Control Vectores, Cordoba, Argentina.
RP Vazquez-Prokopec, GM (reprint author), Univ Buenos Aires, Lab Ecoepidemiol, Buenos Aires, DF, Argentina.
EM gmvazqu@emory.edu
FU National Institutes of Health/National Science Foundation (NIH/NSF) [R01
TW05836]; Fogarty International Center; National Institute of
Environmental Health Sciences (NIEHS); Agencia Nacional de Promocion
Cientifica y Tecnica (Argentina); University of Buenos Aires; I.D.R.C.
Ecohealth Program; UNICEF/UNDP/World Bank/WHO Special Programme for
Research and Training in Tropical Diseases (TDR)
FX This study was supported by awards from the National Institutes of
Health/National Science Foundation (NIH/NSF) Ecology of Infectious
Disease program award R01 TW05836 funded by the Fogarty International
Center and the National Institute of Environmental Health Sciences
(NIEHS) to UK and REG, Agencia Nacional de Promocion Cientifica y
Tecnica (Argentina) and University of Buenos Aires to REG. REG
acknowledges with thanks the support of I.D.R.C. Ecohealth Program, and
UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training
in Tropical Diseases (TDR). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 6
Z9 7
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2012
VL 6
IS 8
AR e1788
DI 10.1371/journal.pntd.0001788
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 001YS
UT WOS:000308497100024
PM 22905276
ER
PT J
AU Anderson, CM
Burns, DM
Dodd, KW
Feuer, EJ
AF Anderson, Christy M.
Burns, David M.
Dodd, Kevin W.
Feuer, Eric J.
TI Birth-Cohort-Specific Estimates of Smoking Behaviors for the US
Population
SO RISK ANALYSIS
LA English
DT Article
DE Age; birth cohort; calendar year; smoking behaviors; smoking prevalence;
US population
ID CIGARETTE-SMOKING; CESSATION; AGE
AB We present methods for estimating five-year birth-cohort-specific trends in smoking behavior for individuals born between 1910 and 1984. We combine cross-sectional survey data on smoking behavior from the National Health Interview Surveys (NHIS) conducted between 1965 and 2001 into a single data set. The cumulative incidence of smoking by year of age and calendar year is constructed for each birth cohort from this data set and the effect of differential mortality on ever smoking prevalence is adjusted by modeling the ever smoking prevalence of each cohort for each survey year and back extrapolating that effect to age 30. Cumulative incidence is then scaled to match the ever smoking prevalence at age 30. Survival analyses generate the cumulative cessation among ever smokers across year of age and calendar year and are used to estimate current smoking prevalence. Data from Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health is used to divide those initiating smoking into quintiles of number of cigarettes smoked per day (CPD) and the mean CPD for each quintile in each calendar year is estimated from the NHIS data. For five-year birth cohorts of white, african-american, Hispanic and all race/ethnicity groupings of males and females born between 1910 and 1984, estimates are provided for prevalence of current and ever smoking, incidence of cessation, incidence of initiation, and the distribution of smoking duration and CPD for each calendar year and each single year of age through the year 1999. We believe that we are the first to provide birth-cohort-specific estimates of smoking behaviors for the U.S. population that include distributions of duration of smoking and number of cigarettes per day. These additional elements substantively enhance the utility of these estimates for estimating lung cancer risks.
C1 [Anderson, Christy M.; Burns, David M.] UCSD Sch Med Family & Prevent Med, Del Mar, CA USA.
[Dodd, Kevin W.] NCI, Canc Prevent Div, Biometry Res Grp, Rockville, MD USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Burns, DM (reprint author), 1120 Solana Dr, Del Mar, CA 92014 USA.
EM dburns@ucsd.edu
FU NIAAA NIH HHS [R43 AA019900]
NR 13
TC 27
Z9 27
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0272-4332
J9 RISK ANAL
JI Risk Anal.
PD AUG
PY 2012
VL 32
SU 1
SI SI
BP S14
EP S24
DI 10.1111/j.1539-6924.2011.01703.x
PG 11
WC Public, Environmental & Occupational Health; Mathematics,
Interdisciplinary Applications; Social Sciences, Mathematical Methods
SC Public, Environmental & Occupational Health; Mathematics; Mathematical
Methods In Social Sciences
GA 986KA
UT WOS:000307339300003
PM 22882884
ER
PT J
AU Bloch, M
Backinger, CL
Compton, WM
Conway, K
AF Bloch, Michele
Backinger, Cathy L.
Compton, Wilson M.
Conway, Kevin
TI Standing on the Threshold of Change
SO RISK ANALYSIS
LA English
DT Article
DE Lung cancer; modeling; smoking; tobacco
ID TOBACCO; SMOKING; CANCER
AB Tobacco use remains the nation's leading cause of preventable premature mortality. Lung cancer, one of the many cancers caused by tobacco use, is both the leading cause of cancer death in the United States and the leading cause of male cancer death globally. This special issue of Risk Analysis features the work of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET), which finds that changes in Americans' smoking behaviors that began in the mid 1950s averted nearly 800,000 U.S. lung cancer deaths in the period 1975-2000 alone. However, this figure represents only about 30% of the lung cancer deaths that could potentially have been averted during this period. Despite dramatic declines in smoking prevalence since the mid 1960s, tobacco use is still far too common; today about one in five American adults smokes cigarettes. The tobacco industry's role in promoting tobacco use is now well documented and, as noted by the President's Cancer Panel, "can no more be ignored in seeking solutions to the tobacco problem than mosquitoes can be ignored in seeking to eradicate malaria." Recent developments, including the passage of legislation granting the Food and Drug Administration broad authority to regulate tobacco products, and the entry into force of the Framework Convention on Tobacco Control, an evidence-based treaty developed by the World Health Organization, hold great promise to more swiftly end the epidemic of lung cancer and other tobacco-caused diseases that exacts such a heavy toll in human suffering in the United States and around the world.
C1 [Bloch, Michele; Backinger, Cathy L.] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA.
[Compton, Wilson M.; Conway, Kevin] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
RP Bloch, M (reprint author), NCI, Tobacco Control Res Branch, 6130 Execut Blvd,Rm 4038,MSC 7337, Bethesda, MD 20892 USA.
EM blochm@mail.nih.gov
OI Conway, Kevin/0000-0002-7638-339X
NR 38
TC 1
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0272-4332
J9 RISK ANAL
JI Risk Anal.
PD AUG
PY 2012
VL 32
SU 1
SI SI
BP S1
EP S5
DI 10.1111/j.1539-6924.2011.01643.x
PG 5
WC Public, Environmental & Occupational Health; Mathematics,
Interdisciplinary Applications; Social Sciences, Mathematical Methods
SC Public, Environmental & Occupational Health; Mathematics; Mathematical
Methods In Social Sciences
GA 986KA
UT WOS:000307339300001
PM 22882881
ER
PT J
AU Feuer, EJ
Levy, DT
McCarthy, WJ
AF Feuer, Eric J.
Levy, David T.
McCarthy, William J.
TI The Impact of the Reduction in Tobacco Smoking on US Lung Cancer
Mortality, 1975-2000: An Introduction to the Problem
SO RISK ANALYSIS
LA English
DT Article
DE Population modeling; smoking
ID POLICY SIMULATION-MODEL; MALE BRITISH DOCTORS; CPS-I DATA;
PUBLIC-POLICIES; UNITED-STATES; MULTISTAGE CARCINOGENESIS; CIGARETTE
CONSUMPTION; REDUCING SMOKING; STATISTICS; WOMEN
AB To better understand the contribution of cigarette smoking, and its changing role in lung cancer, this article provides an introduction to a special issue of Risk Analysis, which considers the relationship between smoking and lung cancer death rates during the period 1975-2000 for U.S. men and women aged 30-84 years. Six models are employed, which are part of a consortium of lung cancer modelers funded by National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET). Starting with birth-cohort-specific smoking histories derived from National Health Interview Surveys, three scenarios are modeled: Actual Tobacco Control (observed trends in smoking), Complete Tobacco Control (a counterfactual lower bound on smoking rates that could have been achieved had all smoking ceased after the first Surgeon General's report in 1964), and No Tobacco Control (a counterfactual upper bound on smoking rates if smoking patterns that prevailed before the first studies in the 1950s began to inform the public about the hazards of smoking). Using these three scenarios and the lung cancer models, the number and percentage of lung cancer deaths averted from 1975-2000, among all deaths that could have been averted if tobacco control efforts been immediate and perfect, can be estimated. The variability of the results across multiple models provides a measure of the robustness of the results to model assumptions and structure. The results provide not only a portrait of the achieved impact of tobacco control on lung cancer mortality, but also the bounds of what still needs to be achieved.
C1 [Feuer, Eric J.] NCI, Stat Methodol & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Levy, David T.] Pacific Inst Res & Evaluat, Calverton, MD USA.
[McCarthy, William J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA.
[McCarthy, William J.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
RP Feuer, EJ (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM rf41u@nih.gov
FU National Cancer Institute's Cancer Intervention and Surveillance
Modeling Network (CISNET) lung cancer group [U01CA097450, U01CA097432,
U01CA097415, U01CA097431, U01CA097416, U01CA152956]
FX This work was supported by the National Cancer Institute's Cancer
Intervention and Surveillance Modeling Network (CISNET) lung cancer
group, under grant numbers U01CA097450, U01CA097432, U01CA097415,
U01CA097431, U01CA097416, and U01CA152956.
NR 66
TC 4
Z9 4
U1 3
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0272-4332
EI 1539-6924
J9 RISK ANAL
JI Risk Anal.
PD AUG
PY 2012
VL 32
SU 1
SI SI
BP S6
EP S13
DI 10.1111/j.1539-6924.2011.01745.x
PG 8
WC Public, Environmental & Occupational Health; Mathematics,
Interdisciplinary Applications; Social Sciences, Mathematical Methods
SC Public, Environmental & Occupational Health; Mathematics; Mathematical
Methods In Social Sciences
GA 986KA
UT WOS:000307339300002
PM 22882893
ER
PT J
AU Rosenberg, MA
Feuer, EJ
Yu, BB
Sun, JF
Henley, SJ
Shanks, TG
Anderson, CM
McMahon, PM
Thun, MJ
Burns, DM
AF Rosenberg, Marjorie A.
Feuer, Eric J.
Yu, Binbing
Sun, Jiafeng
Henley, S. Jane
Shanks, Thomas G.
Anderson, Christy M.
McMahon, Pamela M.
Thun, Michael J.
Burns, David M.
TI Cohort Life Tables by Smoking Status, Removing Lung Cancer as a Cause of
Death
SO RISK ANALYSIS
LA English
DT Article
DE Competing risks; life tables; lung cancer and smoking
ID MORTALITY; DISEASE
AB The purpose of this study was to develop life tables by smoking status removing lung cancer as a cause of death. These life tables are inputs to studies that compare the effectiveness of lung cancer treatments or interventions, and provide a way to quantify time until death from causes other than lung cancer. The study combined actuarial and statistical smoothing methods, as well as data from multiple sources, to develop separate life tables by smoking status, birth cohort, by single year of age, and by sex. For current smokers, separate life tables by smoking quintiles were developed based on the average number of cigarettes smoked per day by birth cohort. The end product is the creation of six non-lung-cancer life tables for males and six tables for females: five current smoker quintiles and one for never smokers. Tables for former smokers are linear combinations of the appropriate table based on the current smoker quintile before quitting smoking and the never smoker probabilities, plus added covariates for the smoking quit age and time since quitting.
C1 [Rosenberg, Marjorie A.; Sun, Jiafeng] Univ Wisconsin, Madison, WI 53706 USA.
[Feuer, Eric J.] NCI, Bethesda, MD 20892 USA.
[Yu, Binbing] NIA, Baltimore, MD 21224 USA.
[Henley, S. Jane; Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Shanks, Thomas G.; Anderson, Christy M.; Burns, David M.] Univ Calif San Diego, San Diego, CA 92103 USA.
[McMahon, Pamela M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Rosenberg, MA (reprint author), Univ Wisconsin, 975 Univ Ave, Madison, WI 53706 USA.
EM mrosenberg@bus.wisc.edu
FU NCI [263-MQ-319824, 263-MQ-416726-1]; Clinical and Translational Science
Award (CTSA) program of the National Center for Research Resources,
National Institutes of Health [1UL1RR025011]; Intramural Research
Program of the National Institute on Aging
FX Partially supported by NCI contract numbers 263-MQ-319824 and
263-MQ-416726-1, by Grant 1UL1RR025011 from the Clinical and
Translational Science Award (CTSA) program of the National Center for
Research Resources, National Institutes of Health, and by the Intramural
Research Program of the National Institute on Aging. We acknowledge
Jerry Vaughn of the University of California San Diego for his
contribution on this article.
NR 15
TC 20
Z9 20
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0272-4332
J9 RISK ANAL
JI Risk Anal.
PD AUG
PY 2012
VL 32
SU 1
SI SI
BP S25
EP S38
DI 10.1111/j.1539-6924.2011.01662.x
PG 14
WC Public, Environmental & Occupational Health; Mathematics,
Interdisciplinary Applications; Social Sciences, Mathematical Methods
SC Public, Environmental & Occupational Health; Mathematics; Mathematical
Methods In Social Sciences
GA 986KA
UT WOS:000307339300004
PM 22882890
ER
PT J
AU Haak, LL
Ferriss, W
Wright, K
Pollard, ME
Barden, K
Probus, MA
Tartakovsky, M
Hackett, CJ
AF Haak, Laurel L.
Ferriss, Will
Wright, Kevin
Pollard, Michael E.
Barden, Kirk
Probus, Matt A.
Tartakovsky, Michael
Hackett, Charles J.
TI The electronic Scientific Portfolio Assistant: Integrating scientific
knowledge databases to support program impact assessment
SO SCIENCE AND PUBLIC POLICY
LA English
DT Article
DE funding program evaluation; research portfolio; automated system;
research impact
ID CITATION COUNTS; CHALLENGES; SCIENCE
AB The US National Institutes of Health (NIH) supports basic and applied biomedical research by funding grants and contracts. To measure the outcomes and impact of their programs, NIH staff conduct program evaluations and undertake targeted investigations of research portfolios. Recently, the NIH launched the electronic scientific portfolio assistant (eSPA), a web-based analytics system based on linked scientific databases that provides quantitative information for program officers and planning and evaluation officials managing research portfolios. This system has improved the ability to create and collaboratively refine research portfolios, has reduced the time needed to collect and link outcomes data such as publications and patents, and is providing information used to support research management decisions. After describing the eSPA system, we provide examples of three eSPA evaluation projects that illustrate the impact of this system on NIH evaluation objectives.
C1 [Haak, Laurel L.; Pollard, Michael E.; Barden, Kirk; Probus, Matt A.] Thomson Reuters, Discovery Log, Rockville, MD 20850 USA.
[Ferriss, Will; Wright, Kevin; Tartakovsky, Michael; Hackett, Charles J.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Haak, LL (reprint author), Thomson Reuters, Discovery Log, 1455 Res Blvd,2nd Floor, Rockville, MD 20850 USA.
EM laurelhaak@gmail.com
RI Haak, Laurel/C-4986-2008;
OI Haak, Laurel/0000-0001-5109-3700; Hackett, Charles/0000-0003-4586-9669
NR 30
TC 3
Z9 3
U1 4
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0302-3427
J9 SCI PUBL POLICY
JI Sci. Public Policy
PD AUG
PY 2012
VL 39
IS 4
BP 464
EP 475
DI 10.1093/scipol/scs030
PG 12
WC Management; Planning & Development; Public Administration
SC Business & Economics; Public Administration
GA 996AV
UT WOS:000308057300006
ER
PT J
AU de Silva, U
Zhou, ZL
Brown, BA
AF de Silva, Udesh
Zhou, Zhaoli
Brown, Bernard A., II
TI Structure of Aeropyrum pernix fibrillarin in complex with natively bound
S-adenosyl-l-methionine at 1.7 A resolution
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
DE fibrillarin; S-adenosyl-l-methionine; methyltransferases; Aeropyrum
pernix
ID RNA; METHYLTRANSFERASE; MODEL
AB Fibrillarin is the key methyltransferase associated with the C/D class of small nuclear ribonucleoproteins (snRNPs) and participates in the preliminary step of pre-ribosomal rRNA processing. This molecule is found in the fibrillar regions of the eukaryotic nucleolus and is involved in methylation of the 2'-O atom of ribose in rRNA. Human fibrillarin contains an N-terminal GAR domain, a central RNA-binding domain comprising an RNP-2-like superfamily consensus sequence and a catalytic C-terminal helical domain. Here, Aeropyrum pernix fibrillarin is described, which is homologous to the C-terminal domain of human fibrillarin. The protein was crystallized with an S-adenosyl-l-methionine (SAM) ligand bound in the active site. The molecular structure of this complex was solved using X-ray crystallography at a resolution of 1.7 angstrom using molecular replacement with fibrillarin structural homologs. The structure shows the atomic details of SAM and its active-site interactions; there are a number of conserved residues that interact directly with the cofactor. Notably, the adenine ring of SAM is stabilized by pp interactions with the conserved residue Phe110 and by electrostatic interactions with the Asp134, Ala135 and Gln157 residues. The pp interaction appears to play a critical role in stabilizing the association of SAM with fibrillarin. Furthermore, comparison of A. pernix fibrillarin with homologous structures revealed different orientations of Phe110 and changes in a-helix 6 of fibrillarin and suggests key differences in its interactions with the adenine ring of SAM in the active site and with the C/D RNA. These differences may play a key role in orienting the SAM ligand for catalysis as well as in the assembly of other ribonucleoproteins and in the interactions with C/D RNA.
C1 [Brown, Bernard A., II] Womble Carlyle Sandridge & Rice LLP, Winston Salem, NC 27101 USA.
[de Silva, Udesh] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Zhaoli] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
RP Brown, BA (reprint author), Womble Carlyle Sandridge & Rice LLP, 1 W 4th St, Winston Salem, NC 27101 USA.
EM bebrown@wcsr.com
FU National Institutes of Health [GM069699]
FX We would like to thank Dr David R. Davies of National Institutes of
Health for proofreading the manuscript and NIH/NIDDK/LMB for their
generous support with computer resources. This research was supported in
part by National Institutes of Health Grant GM069699 to BAB. This
research was initiated in the Department of Chemistry, Wake Forest
University (ZZ and BAB) and the Department of Biochemistry, Wake Forest
University School of Medicine (UdS).
NR 25
TC 2
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD AUG
PY 2012
VL 68
BP 854
EP 859
DI 10.1107/S1744309112026528
PN 8
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 984UL
UT WOS:000307217700002
PM 22869109
ER
PT J
AU Ma, JC
Tang, WK
Esser, L
Pastan, I
Xia, D
AF Ma, Jichun
Tang, Wai Kwan
Esser, Lothar
Pastan, Ira
Xia, Di
TI Characterization of crystals of an antibody-recognition fragment of the
cancer differentiation antigen mesothelin in complex with the
therapeutic antibody MORAb-009
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
DE mesothelin; MORAb-009; monoclonal antibodies
ID MOLECULAR-REPLACEMENT; OVARIAN; EXPRESSION
AB The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 764) were crystallized. The crystals of the Fab diffracted X-rays to 1.75 angstrom resolution and had the symmetry of space group P41212, with unit-cell parameters a = b = 140.6, c=282.0 angstrom. The crystals of the mesothelinFab complex diffracted to 2.6 angstrom resolution and belonged to the hexagonal space group P64, with unit-cell parameters a = b = 146.2, c = 80.9 angstrom. Structural analyses of these molecules are in progress.
C1 [Ma, Jichun; Tang, Wai Kwan; Esser, Lothar; Xia, Di] NIH, Lab Cell Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pastan, Ira] NIH, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Xia, D (reprint author), NIH, Lab Cell Biol, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM dixia@helix.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; CRADA;
Morphotek Inc.
FX The authors wish to thank the staff of the SER-CAT beamline at APS, ANL
for their assistance in data collection. This research was supported by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research and by a CRADA with Morphotek Inc. We also
thank George Leiman for his editorial assistance during the preparation
of this manuscript.
NR 21
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD AUG
PY 2012
VL 68
BP 950
EP 953
DI 10.1107/S1744309112028229
PN 8
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 984UL
UT WOS:000307217700023
PM 22869130
ER
PT J
AU McGuire, LI
Peden, AH
Orru, CD
Wilham, JM
Appleford, NE
Mallinson, G
Andrews, M
Head, MW
Caughey, B
Will, RG
Knight, RSG
Green, AJE
AF McGuire, Lynne I.
Peden, Alexander H.
Orru, Christina D.
Wilham, Jason M.
Appleford, Nigel E.
Mallinson, Gary
Andrews, Mary
Head, Mark W.
Caughey, Byron
Will, Robert G.
Knight, Richard S. G.
Green, Alison J. E.
TI Real time quaking-induced conversion analysis of cerebrospinal fluid in
sporadic Creutzfeldt-Jakob disease
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID PRION DETECTION; CLASSIFICATION; DIAGNOSIS; PROTEIN; 14-3-3-PROTEIN;
UTILITY; PRP
AB Objective: Current cerebrospinal fluid (CSF) tests for sporadic CreutzfeldtJakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3, which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real time quaking-induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD. Methods: An exploratory study was undertaken that analyzed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples, 56 were from sCJD patients (30 female, 26 male; aged 3184 years; mean age, 62.3 +/- 13.5 years), and 52 were from control patients (26 female, 26 male; aged 4384 years; mean age, 67.8 +/- 10.4 years). A confirmatory group of 118 patients was subsequently examined that consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male; aged 3982 years; mean age, 67.5 +/- 9.0 years) and 51 control cases (26 female, 25 male; aged 3687 years; mean age, 63.5 +/- 11.6 years). Results: The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study, which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100%, respectively. Interpretation: This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests. ANN NEUROL 2012;72:278285.
C1 [McGuire, Lynne I.; Peden, Alexander H.; Andrews, Mary; Head, Mark W.; Will, Robert G.; Knight, Richard S. G.; Green, Alison J. E.] Univ Edinburgh, Natl Creutzfeldt Jakob Dis Res & Surveillance Uni, Edinburgh EH4 2XU, Midlothian, Scotland.
[Orru, Christina D.; Wilham, Jason M.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Appleford, Nigel E.; Mallinson, Gary] Bristol Inst Transfus Sci, Natl Hlth Serv Blood & Transplant, Bristol, Avon, England.
RP Green, AJE (reprint author), Univ Edinburgh, Western Gen Hosp, Natl CJD Res & Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
EM Alison.Green@ed.ac.uk
OI Head, Mark/0000-0003-2034-8613
FU Alliance BioSecure [ERI REF:017476]; University of Edinburgh Development
Trust; Scottish Government's Chief Scientists Office, Government of
Scotland [CZB/4/688]; Department of Health; Scottish Home Office
Department of Health [121/5061]; Intramural Research Program of the NIH
National Institute of Allergy and Infectious Diseases; Department of
Health (England); Medical Research Council [G1000681]
FX This study has been funded by Alliance BioSecure (ERI REF:017476), a
Small Projects Grant from the University of Edinburgh Development Trust,
and the Scottish Government's Chief Scientists Office, Government of
Scotland (CZB/4/688) (L. I. M., A. H. P.). The National CJD Research and
Surveillance Unit is funded by the Department of Health and the Scottish
Home Office Department of Health (121/5061) (M. A., M. W. H., R. G. W.,
R. S. G. K., A.J.E.G.). This work was supported in part by the
Intramural Research Program of the NIH National Institute of Allergy and
Infectious Diseases (C.D.O., J.M.W., B. C.) and by the Department of
Health (England; N.E.A., G. M.). The Edinburgh Brain Bank is supported
by the Medical Research Council (G1000681).
NR 20
TC 89
Z9 90
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2012
VL 72
IS 2
BP 278
EP 285
DI 10.1002/ana.23589
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 994QK
UT WOS:000307946000017
PM 22926858
ER
PT J
AU Kwon, EM
Holt, SK
Fu, R
Kolb, S
Williams, G
Stanford, JL
Ostrander, EA
AF Kwon, Erika M.
Holt, Sarah K.
Fu, Rong
Kolb, Suzanne
Williams, Gabrielle
Stanford, Janet L.
Ostrander, Elaine A.
TI Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Androgen pathway; JAK2; HSD17B3; Prostate cancer; Polymorphisms; Genetic
susceptibility
ID SINGLE-NUCLEOTIDE POLYMORPHISM; GENOME-WIDE ASSOCIATION;
AFRICAN-AMERICAN MEN; VARIANTS; SUSCEPTIBILITY; POPULATION; NKX3.1;
TESTOSTERONE; PROPORTIONS; ACTIVATION
AB Background: Prostate cancer (PC) is the most frequently diagnosed solid tumor in U.S. men. Genome-wide association studies (GWAS) have identified over 40 risk-associated single nucleotide polymorphisms (SNPs), including variants in androgen pathway genes (e.g., KLK3 and AR). Androgens are important in PC and genes involved in this pathway are therefore candidates for conferring susceptibility to PC. Methods: In this hypothesis-testing study, we evaluated PC risk in association with SNPs in 22 candidate genes involved in androgen metabolism or interactions with the androgen receptor (AR). A total of 187 SNPs were genotyped in 1458 cases and 1351 age-matched controls from a population-based study. PC risk was estimated using adjusted unconditional logistic regression and multinomial regression models. Results: Single SNP analyses showed evidence (p < 0.05) for associations with 14 SNPs in 9 genes: NKX3.1, HSD17B3, AKR1C3, SULT2A1, CYP17A1, KLK3, JAK2, NCOA4 and STAT3. The most significant result was observed for rs2253502 in HSD17B3 (odds ratio, OR = 0.57, 95% CI: 0.39-0.84). In addition, five SNPs in four genes (CYP17A1, HSD17B4, NCOA4, and SULT2A1) were associated with more aggressive disease (p < 0.01). Conclusions: Our results replicate previously reported associations for SNPs in CYP17A1, HSD17B3, ARK1C3, NKX3.1, NCOA4 and KLK3. In addition, novel associations were observed for SNPs in JAK2, HSD17B4, and SULT2A1. These results will require replication in larger studies. Published by Elsevier Ltd.
C1 [Kwon, Erika M.; Williams, Gabrielle; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD 21205 USA.
[Holt, Sarah K.; Fu, Rong; Kolb, Suzanne; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98103 USA.
[Stanford, Janet L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,Bldg 50,Room 5351, Bethesda, MD 20892 USA.
EM kwone@mail.nih.gov; skholt@fhcrc.org; rfu@fhcrc.org; skolb@fhcrc.org;
gabego@hotmail.com; jstanfor@fhcrc.org; eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU National Cancer Institute [RO1-CA056678, R01-CA092579]; Fred Hutchinson
Cancer Research Center
FX We would like to thank all participants of this study for their time and
effort. This work was supported by the Intramural Program of the
National Human Genome Research Institute, by grants RO1-CA056678 and
R01-CA092579 from the National Cancer Institute with additional support
from the Fred Hutchinson Cancer Research Center.
NR 50
TC 14
Z9 16
U1 3
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2012
VL 36
IS 4
BP 347
EP 353
DI 10.1016/j.canep.2012.04.002
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 984UD
UT WOS:000307216700014
PM 22542949
ER
PT J
AU Slusky, DA
Metayer, C
Aldrich, MC
Ward, MH
Lea, CS
Selvin, S
Buffler, PA
AF Slusky, Danna A.
Metayer, Catherine
Aldrich, Melinda C.
Ward, Mary H.
Lea, C. Suzanne
Selvin, Steve
Buffler, Patricia A.
TI Reliability of maternal-reports regarding the use of household
pesticides: Experience from a case-control study of childhood leukemia
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Reliability; Case-control study; Leukemia; Recall bias
ID OCCUPATIONAL EXPOSURES; CHEMICAL-EXPOSURE; RISK; WORKERS; CANCER;
GENOTOXICITY; CHILDREN; GERMANY; PARENTS
AB Introduction: Self-reported household pesticide use has been associated with higher risk of childhood leukemia in a number of case-control studies. The aim of this study is to assess the reliability of self-reported household use of pesticides and potential differences in reliability by case-control status, and by socio-demographic characteristics. Methods: Analyses are based on a subset of the Northern California Childhood Leukemia Study population. Eligible households included those with children less than 8 years old who lived in the same residence since diagnosis (reference date for controls). The reliability was based on two repeated in-person interviews. Kappa, percent positive and negative agreements were used to assess reliability of responses to ever/never use of six pesticides categories. Results: Kappa statistics ranged from 0.31 to 0.61 (fair to substantial agreement), with 9 out of the 12 tests indicating moderate agreement. The percent positive agreement ranged from 46 to 80% and the percent negative agreement from 54 to 95%. Reliability for all pesticide types as assessed by the three reliability measures did not differ significantly for cases and controls as confirmed by bootstrap analysis. For most pesticide types, Kappa and percent positive agreement were higher for non-Hispanics than Hispanics and for households with higher income vs. lower income. Conclusions: Reproducibility of maternal-reported pesticide use was moderate to high and was similar among cases and controls suggesting that differential recall is not likely to be a major source of bias. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Slusky, Danna A.] Univ Calif Berkeley, Div Epidemiol, Sch Publ Hlth, Berkeley, CA 94704 USA.
[Aldrich, Melinda C.] Vanderbilt Univ, Med Ctr, Dept Thorac Surg, Nashville, TN USA.
[Aldrich, Melinda C.] Vanderbilt Univ, Med Ctr, Div Epidemiol, Nashville, TN USA.
[Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Lea, C. Suzanne] E Carolina Univ, Dept Publ Hlth, Brody Sch Med, Greenville, NC USA.
RP Slusky, DA (reprint author), Univ Calif Berkeley, Div Epidemiol, Sch Publ Hlth, 1995 Univ Ave,Ste 460, Berkeley, CA 94704 USA.
EM dannaaharon@gmail.com
RI Aldrich, Melinda/C-7783-2013
FU National Institute of Environmental Health Sciences [PS42 ES04705, R01
ES09137]; National Cancer Institute
FX This work was supported by the National Institute of Environmental
Health Sciences (PS42 ES04705 and R01 ES09137). This work was also
partly supported by the intramural research program of the National
Cancer Institute.
NR 28
TC 5
Z9 5
U1 2
U2 19
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2012
VL 36
IS 4
BP 375
EP 380
DI 10.1016/j.canep.2011.12.009
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 984UD
UT WOS:000307216700018
PM 22277328
ER
PT J
AU Laiyemo, AO
Doubeni, C
Pinsky, PF
Doria-Rose, VP
Sanderson, AK
Bresalier, R
Weissfeld, J
Schoen, RE
Marcus, PM
Prorok, PC
Berg, CD
AF Laiyemo, Adeyinka O.
Doubeni, Chyke
Pinsky, Paul F.
Doria-Rose, V. Paul
Sanderson, Andrew K., II
Bresalier, Robert
Weissfeld, Joel
Schoen, Robert E.
Marcus, Pamela M.
Prorok, Philip C.
Berg, Christine D.
TI Factors associated with inadequate colorectal cancer screening with
flexible sigmoidoscopy
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Flexible sigmoidoscopy; Colorectal cancer; Inadequate screening; Colon
polyp
ID BASE-LINE FINDINGS; RANDOMIZED-TRIAL; PROSTATE; LUNG; COLONOSCOPY
AB Background and study aim: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Methods: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was <50 cm or visual inspection was limited to <90% of the mucosal surface but without detection of a polyp or mass). Results: Of 7084 (11%) participants with inadequate FSG at baseline, 6496 (91.7%) had <50 cm depth of insertion (75.3% due to patient discomfort) and 500 (7.1%) participants had adequate depth of insertion but suboptimal bowel preparation. Compared to 55-59 year age group, advancing age in 5-year increments (odds ratios (OR) from 1.08 to 1.51) and female sex (OR = 2.40; 95% confidence interval (CI): 2.27-2.54) were associated with inadequate FSG. Obesity (BMI >30 kg/m(2)) was associated with reduced odds (OR = 0.67; 95% CI: 0.62-0.72). Inadequate FSG screening at baseline was associated with inadequate FSG at repeat screening (OR = 6.24; 95% CI: 5.78-6.75). Conclusions: Sedation should be considered for patients with inadequate FSG or an alternative colorectal cancer screening method should be recommended. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Laiyemo, Adeyinka O.; Sanderson, Andrew K., II] Howard Univ, Coll Med, Div Gastroenterol, Dept Med, Washington, DC 20060 USA.
[Laiyemo, Adeyinka O.; Marcus, Pamela M.; Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Doubeni, Chyke] Univ Massachusetts, Dept Family Med, Worcester, MA 01655 USA.
[Pinsky, Paul F.; Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Doria-Rose, V. Paul] NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Bresalier, Robert] MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Weissfeld, Joel; Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA.
RP Laiyemo, AO (reprint author), Howard Univ, Coll Med, Div Gastroenterol, Dept Med, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM adeyinka.laiyemo@howard.edu; Chyke.Doubeni@umassmed.edu;
pinskyp@mail.nih.gov; doriarop@mail.nih.gov;
andrew.sanderson@howard.edu; rbresali@mdanderson.org; jwepid@pitt.edu;
rschoen@pitt.edu; marcusp@mail.nih.gov; prorokp@mail.nih.gov;
bergc@mail.nih.gov
RI Berg , Christine/K-1047-2014
FU Division of Cancer Prevention, National Cancer Institute, National
Institutes of Health; National Cancer Institute's new faculty
recruitment supplement to the Comprehensive Minority Institution/Cancer
Center Partnership between Howard University Cancer Center; Sidney
Kimmel Comprehensive Cancer Center of Johns Hopkins University
[5U54CA091431-09 S1]; National Cancer Institute [5K01CA127118-03]
FX The study was funded by the Division of Cancer Prevention, National
Cancer Institute, National Institutes of Health. The funding agency had
a role in the design and reporting of the study and in the decision to
submit the manuscript for publication and approved the final version of
the manuscript.; Dr Laiyemo is supported by the National Cancer
Institute's new faculty recruitment supplement to the Comprehensive
Minority Institution/Cancer Center Partnership between Howard University
Cancer Center and Sidney Kimmel Comprehensive Cancer Center of Johns
Hopkins University (5U54CA091431-09 S1). Dr. Doubeni is supported by a
mentored career development award (5K01CA127118-03) from the National
Cancer Institute
NR 17
TC 2
Z9 2
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2012
VL 36
IS 4
BP 395
EP 399
DI 10.1016/j.canep.2012.10.013
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 984UD
UT WOS:000307216700022
PM 22112544
ER
PT J
AU London, WT
McGlynn, KA
AF London, W. Thomas
McGlynn, Katherine A.
TI Can Propranalol Prevent Hepatocellular Carcinoma?
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID BETA-BLOCKERS; RISK-FACTORS; HEPATITIS-C; CANCER; CIRRHOSIS;
EPIDEMIOLOGY; ENTECAVIR; THERAPY
AB beta-Adrenergic signaling is involved in many processes that may contribute to cancer progression. In this issue of the journal (beginning on page 1007), Nkontchou and colleagues report their retrospective observational finding that the beta-blocker propranolol was associated with a highly statistically significant reduction in the incidence of hepatocellular carcinoma in patients with advanced cirrhosis and related esophageal varices. This surprising finding requires confirmation, but the result is biologically plausible. Epidemiologic studies have linked beta-blockers with reduced rates of metastasis of other cancers and reduced cancer mortality. Laboratory studies suggest biologic mechanisms for anticancer effects of beta-blockers. Cancer Prev Res; 5(8); 989-91. (C) 2012 AACR.
C1 [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP London, WT (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM thomas.london@fccc.edu
FU Intramural NIH HHS [ZIA CP010158-11]
NR 23
TC 5
Z9 5
U1 0
U2 3
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 AUG
PY 2012
VL 5
IS 8
BP 989
EP 991
DI 10.1158/1940-6207.CAPR-12-0247
PG 3
WC Oncology
SC Oncology
GA 998FS
UT WOS:000308223500001
PM 22869451
ER
PT J
AU Liu, Q
Yi, L
Sadiq-Ali, S
Koontz, SM
Wood, A
Zhu, N
Jackson, SH
AF Liu, Q.
Yi, L.
Sadiq-Ali, S.
Koontz, S. M.
Wood, A.
Zhu, N.
Jackson, S. H.
TI PP2A-dependent control of transcriptionally active FOXO3a in CD8(+)
central memory lymphocyte survival requires p47(phox)
SO CELL DEATH & DISEASE
LA English
DT Article
DE forkhead box O3a; protein phosphatase 2A; p47phox; memory T cell
ID CHRONIC GRANULOMATOUS-DISEASE; PROTEIN PHOSPHATASE 2A; T-CELLS;
LISTERIA-MONOCYTOGENES; IMMUNE-RESPONSES; NADPH OXIDASE; BIM;
PHOSPHORYLATION; INHIBITION; APOPTOSIS
AB Forkhead box O3a (FOXO3a) transcription factor is regulated by complex post-translational modifications that allow for transcriptional control of various apoptosis factors including pro-apoptotic Bim. Although it has been shown that kinases phosphorylate FOXO3a in memory T cells, the role of protein phosphatases in the control of memory T lymphocyte FOXO3a function is less clear. Here, we report that FOXO3a is dephosphorylated (activated) by a protein phosphatase 2A (PP2A)-dependent mechanism in CD8(+) memory lymphocytes (Tm) during Listeria monocytogenes (Lm) infection, which allows for enhanced Bim transcription in nicotinamide adenine dinucleotide phosphate-oxidase p47(phox)-deficient (p47(phox-/-)) Tm. Consequently, CD8(+) Tm from Lm-infected p47(phox-/-) mice express significantly higher levels of each pro-apoptotic Bim protein isoform. Furthermore, there was a profound reduction in the accumulation of CD8(+) T central memory (Tcm) cells in infected p47(phox-/-) spleens, and 65% p47(phox-/-) mouse moribundity following secondary Lm reinfection compared with 25% in wild-type mice. Notably, blocking PP2A activity attenuated FOXO3 activation and Bim transcription in p47(phox-/-) CD8(+) memory lymphocytes. Our findings indicate a critical role for p47(phox) in a dynamic interplay between PP2A and FOXO3a that regulates pro-apoptotic Bim transcription in CD8(+) memory lymphocytes during infection. Cell Death and Disease (2012) 3, e375; doi: 10.1038/cddis.2012.118; published online 23 August 2012
C1 [Liu, Q.; Yi, L.; Sadiq-Ali, S.; Koontz, S. M.; Wood, A.; Zhu, N.; Jackson, S. H.] NIAID, Mol Trafficking Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA.
RP Jackson, SH (reprint author), NIAID, Mol Trafficking Unit, Lab Host Def, NIH, CRC Bldg,5 W Labs,Room 5-3942,10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA.
EM sjackson@niaid.nih.gov
FU Division of Intramural Research of the National Institutes of
Health/National Institute of Allergy and Infectious Diseases; National
Institutes of Health/National Institute on Minority Health and Health
Disparities
FX We thank Kevin Gardner for helpful discussions and critique of this
manuscript. We also thank Thomas Leto, Jonathan Yewdell, and Jason
Brenchley for careful review and critique of this manuscript. This
research was supported by the Division of Intramural Research of the
National Institutes of Health/National Institute of Allergy and
Infectious Diseases. This was also partially supported by the National
Institutes of Health/National Institute on Minority Health and Health
Disparities.
NR 41
TC 4
Z9 4
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD AUG
PY 2012
VL 3
AR e375
DI 10.1038/cddis.2012.118
PG 10
WC Cell Biology
SC Cell Biology
GA 002SC
UT WOS:000308553800016
PM 22914323
ER
PT J
AU Taraska, JW
AF Taraska, Justin W.
TI Mapping membrane protein structure with fluorescence
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID SINGLE-MOLECULE FRET; SHAKER K+ CHANNEL; NEUROTRANSMITTER TRANSPORTER
HOMOLOG; NUCLEOTIDE-GATED CHANNELS; ION CHANNELS;
CONFORMATIONAL-CHANGES; POTASSIUM CHANNEL; VOLTAGE SENSOR; CI-VSP;
GLUTAMATE TRANSPORTERS
AB Membrane proteins regulate many cellular processes including signaling cascades, ion transport, membrane fusion, and cell-to-cell communications. Understanding the architecture and conformational fluctuations of these proteins is critical to understanding their regulation and functions. Fluorescence methods including intensity mapping, fluorescence resonance energy transfer (FRET), and photo-induced electron transfer, allow for targeted measurements of domains within membrane proteins. These methods can reveal how a protein is structured and how it transitions between different conformational states. Here, I will review recent work done using fluorescence to map the structures of membrane proteins, focusing on how each of these methods can be applied to understanding the dynamic nature of individual membrane proteins and protein complexes.
C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Taraska, JW (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM justin.taraska@nih.gov
RI Taraska, Justin/H-8876-2016
OI Taraska, Justin/0000-0001-5355-9535
FU intramural research program at the National Heart Lung and Blood
Institute, National Institutes of Health
FX J.W. Taraska is supported by the intramural research program at the
National Heart Lung and Blood Institute, National Institutes of Health.
NR 61
TC 14
Z9 14
U1 2
U2 29
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD AUG
PY 2012
VL 22
IS 4
BP 507
EP 513
DI 10.1016/j.sbi.2012.02.004
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 002FG
UT WOS:000308516800016
PM 22445227
ER
PT J
AU Fang, F
Wirdefeldt, K
Jacks, A
Kamel, F
Ye, WM
Chen, HL
AF Fang, Fang
Wirdefeldt, Karin
Jacks, Andreas
Kamel, Freya
Ye, Weimin
Chen, Honglei
TI CNS infections, sepsis and risk of Parkinson's disease
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Parkinson's disease; central nervous system infections; sepsis;
registers
ID NEURODEGENERATIVE DISEASES; NEUROINFLAMMATION; INFLUENZA
AB Background Neuroinflammation may play an important role in the aetiology of Parkinson's disease ( PD); however, little is known about infections in relation to future PD risk.
Methods We conducted a register-based nested case-control study in Sweden to examine infections of the central nervous system (CNS) and sepsis in relation to PD with 18 648 patients and 93 240 matched controls. We defined the index date as the date of first recorded PD diagnosis in the Swedish Patient Register.
Results Overall, PD patients were more likely to have a previous hospitalization for CNS infections [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] or sepsis (OR = 1.6, 95% CI: 1.4-1.7) than controls, largely due to hospitalizations in the year before PD identification (CNS infections: OR = 3.0, 95% CI: 1.6-5.7; sepsis: OR = 3.5, 95% CI: 3.0-4.0). However, we found that subjects with multiple CNS infections at least 5 years before the index date had higher PD occurrence than those without CNS infections (OR = 3.3, 95% CI: 1.4-8.2), whereas the corresponding OR for sepsis was 1.4 (95% CI: 0.8-2.4). After the index date, PD patients were more likely to be hospitalized for CNS infections [hazard ratio (HR) =1.8, 95% CI: 1.2-2.7] or sepsis (HR = 2.2, 95% CI: 2.1-2.4) than controls.
Conclusions This study provides preliminary evidence for an association between CNS infections, but not sepsis, and a higher future risk of PD. It also shows that PD patients were more prone to CNS infections and sepsis than controls.
C1 [Kamel, Freya; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Jacks, Andreas] Natl Inst Hlth & Welf, Dept Infect Dis Surveillance & Control, Epidemiol Surveillance & Response Unit, Helsinki, Finland.
[Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Fang, Fang; Wirdefeldt, Karin; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615; Chen,
Honglei/0000-0003-3446-7779
FU Swedish Research Council (SIMSAM) [80748301]; National Institutes of
Health; National Institute of Environmental Health Sciences
[Z01-ES-101986]; Swedish Society for Medical Research; Swedish Medical
Society; Parkinson Foundation in Sweden; Hjarnfonden (postdoctoral
fellowship)
FX The Swedish Research Council (SIMSAM Grant No. 80748301); intramural
research program of the National Institutes of Health, the National
Institute of Environmental Health Sciences (Z01-ES-101986 and unmet need
grant); the Swedish Society for Medical Research; the Swedish Medical
Society and the Parkinson Foundation in Sweden; Hjarnfonden
(postdoctoral fellowship to F.F.).
NR 30
TC 6
Z9 7
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD AUG
PY 2012
VL 41
IS 4
BP 1042
EP 1049
DI 10.1093/ije/dys052
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 998IV
UT WOS:000308232200022
PM 22523201
ER
PT J
AU Kitahara, CM
Wang, SS
Melin, BS
Wang, ZM
Braganza, M
Inskip, PD
Albanes, D
Andersson, U
Freeman, LEB
Buring, JE
Carreon, T
Feychting, M
Gapstur, SM
Gaziano, JM
Giles, GG
Hallmans, G
Hankinson, SE
Henriksson, R
Hsing, AW
Johansen, C
Linet, MS
McKean-Cowdin, R
Michaud, DS
Peters, U
Purdue, MP
Rothman, N
Ruder, AM
Sesso, HD
Severi, G
Shu, XO
Stevens, VL
Visvanathan, K
Waters, MA
White, E
Wolk, A
Zeleniuch-Jacquotte, A
Zheng, W
Hoover, R
Fraumeni, JF
Chatterjee, N
Yeager, M
Chanock, SJ
Hartge, P
Rajaraman, P
AF Kitahara, Cari M.
Wang, Sophia S.
Melin, Beatrice S.
Wang, Zhaoming
Braganza, Melissa
Inskip, Peter D.
Albanes, Demetrius
Andersson, Ulrika
Freeman, Laura E. Beane
Buring, Julie E.
Carreon, Tania
Feychting, Maria
Gapstur, Susan M.
Gaziano, J. Michael
Giles, Graham G.
Hallmans, Goran
Hankinson, Susan E.
Henriksson, Roger
Hsing, Ann W.
Johansen, Christoffer
Linet, Martha S.
McKean-Cowdin, Roberta
Michaud, Dominique S.
Peters, Ulrike
Purdue, Mark P.
Rothman, Nathaniel
Ruder, Avima M.
Sesso, Howard D.
Severi, Gianluca
Shu, Xiao-Ou
Stevens, Victoria L.
Visvanathan, Kala
Waters, Martha A.
White, Emily
Wolk, Alicja
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Hoover, Robert
Fraumeni, Joseph F., Jr.
Chatterjee, Nilanjan
Yeager, Meredith
Chanock, Stephen J.
Hartge, Patricia
Rajaraman, Preetha
TI Association between adult height, genetic susceptibility and risk of
glioma
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Height; brain cancer; glioma; cancer; epidemiology
ID BASE-LINE CHARACTERISTICS; BODY-MASS INDEX; GENOME-WIDE ASSOCIATION;
CANCER-RISK; PROSPECTIVE COHORT; WOMENS HEALTH; LEG LENGTH; GROWTH;
MORTALITY; DESIGN
AB Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub- types, and investigated effect modification by genetic susceptibility to the disease.
Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants.
Results Among men, we found a positive association between height and glioma risk (epsilon 190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (epsilon 175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk.
Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.
C1 [Kitahara, Cari M.; Wang, Zhaoming; Braganza, Melissa; Inskip, Peter D.; Albanes, Demetrius; Freeman, Laura E. Beane; Hsing, Ann W.; Linet, Martha S.; Purdue, Mark P.; Rothman, Nathaniel; Hoover, Robert; Fraumeni, Joseph F., Jr.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Melin, Beatrice S.; Andersson, Ulrika; Henriksson, Roger] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Wang, Zhaoming; Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Gaithersburg, MD USA.
[Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Carreon, Tania; Ruder, Avima M.; Waters, Martha A.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
[Feychting, Maria; Wolk, Alicja] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden.
[Hankinson, Susan E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Henriksson, Roger] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Johansen, Christoffer] Danish Canc Soc, Unit Survivorship, Copenhagen, Denmark.
[McKean-Cowdin, Roberta] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Michaud, Dominique S.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA.
RP Kitahara, CM (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7053,6120 Execut Blvd, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI Ruder, Avima/I-4155-2012; Michaud, Dominique/I-5231-2014; Albanes,
Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; Beane Freeman,
Laura/C-4468-2015; Kitahara, Cari/R-8267-2016;
OI Ruder, Avima/0000-0003-0419-6664; Purdue, Mark/0000-0003-1177-3108;
Beane Freeman, Laura/0000-0003-1294-4124; Giles,
Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU NCI, National Institutes of Health; American Cancer Society; Centers for
Disease Control and Prevention's National Program of Cancer Registries
and cancer registries; National Cancer Institute's Surveillance
Epidemiology and End Results Program; National Cancer Institute [R01
CA098661, P30 CA016087]; National Institute of Environmental Health
Sciences [ES000260]; National Institutes of Health [CA 97193, CA 34944,
CA 40360, HL 26490, HL 34595]; State of Maryland; Maryland Cigarette
Restitution Fund; National Program of Cancer Registries of the Centers
for Disease Control and Prevention; Division of Cancer Epidemiology and
Genetics; Division of Cancer Prevention, NCI, National Institutes of
Health (NIH); Department of Health and Human Services (DHHS); VicHealth;
Australian National Health and Medical Research Council [209057, 251533,
396414]; NCI [K05CA154337]; NIH Office of Dietary Supplements (ODS)
FX This work was supported in part by the Intramural Research Program of
the NCI, National Institutes of Health.; For CPS-II Nutrition Cohort:
The Cancer Prevention Studies are supported by the American Cancer
Society. Efforts of the ACS the study management group to maintain and
follow the cohort are acknowledged. ACS investigators also acknowledge
the contributions from central cancer registries supported through the
Centers for Disease Control and Prevention's National Program of Cancer
Registries and cancer registries supported by the National Cancer
Institute's Surveillance Epidemiology and End Results Program.; For
NYUWHS: The NYUWHS is supported by National Cancer Institute grants R01
CA098661 and P30 CA016087 and by Center grant ES000260 from the National
Institute of Environmental Health Sciences.; For PHS: The PHS is
supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595
from the National Institutes of Health.; For CLUE: 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, USA;
www.fha.state.md.us/cancer/registry/, 410-767-4055. The authors
acknowledge the State of Maryland, the Maryland Cigarette Restitution
Fund and the National Program of Cancer Registries of the Centers for
Disease Control and Prevention for the funds that support the collection
and availability of the cancer registry data. The findings and
conclusions of this report are those of the authors and do not
necessarily represent the views of the Maryland Cancer Registry.; For
PLCO: This research was supported by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics and by contracts from
the Division of Cancer Prevention, NCI, National Institutes of Health
(NIH) and Department of Health and Human Services (DHHS). The authors
thank Drs Christine Berg and Philip Prorok, Division of Cancer
Prevention, NCI, the Screening Center investigators and staff of the
PLCO cancer screening trial, Mr Tom Riley and staff, Information
Management Services, Inc., Ms Barbara O'Brien and staff, Westat, Inc.,
Mr Tim Sheehy and staff, DNA Extraction and Staging Laboratory,
SAIC-Frederick, Inc. and Ms Jackie King and staff, BioReliance, Inc.;
For MCCS: Infrastructure support for the MCCS recruitment and follow-up
is provided by the Cancer Council Victoria, and cohort recruitment was
partly funded by VicHealth. This work using the MCCS was supported by
the Australian National Health and Medical Research Council (grant
numbers 209057, 251533 and 396414).; For VITAL: Grant K05CA154337 is
funded by the NCI and the NIH Office of Dietary Supplements (ODS).
NR 47
TC 7
Z9 7
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD AUG
PY 2012
VL 41
IS 4
BP 1075
EP 1085
DI 10.1093/ije/dys114
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 998IV
UT WOS:000308232200026
PM 22933650
ER
PT J
AU Elmariah, S
Delaney, JAC
Bluemke, DA
Budoff, MJ
O'Brien, KD
Fuster, V
Kronmal, RA
Halperin, JL
AF Elmariah, Sammy
Delaney, Joseph A. C.
Bluemke, David A.
Budoff, Matthew J.
O'Brien, Kevin D.
Fuster, Valentin
Kronmal, Richard A.
Halperin, Jonathan L.
TI Associations of LV Hypertrophy With Prevalent and Incident Valve
Calcification Multi-Ethnic Study of Atherosclerosis
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE aortic valve; calcification; left ventricular mass; mitral valve annulus
ID MITRAL ANNULAR CALCIFICATION; LEFT-VENTRICULAR HYPERTROPHY;
COMPUTED-TOMOGRAPHY; DISEASE; SCLEROSIS; CALCIUM; RISK; MESA;
HYPERTENSION; MORBIDITY
AB OBJECTIVES The aim of this study was to evaluate the relationship between percentage of predicted left ventricular mass (%PredLVM) and valve calcification in the MESA (Multi-Ethnic Study of Atherosclerosis) study.
BACKGROUND Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood.
METHODS The MESA study is a longitudinal cohort study of men and women 45 to 84 years of age without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling.
RESULTS Prevalent AVC was observed in 630, and MAC was observed in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, sex, body mass index (BMI), ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (odds ratio [OR]: 1.18/SD increase in %PredLVM [95% confidence interval (CI): 1.08 to 1.30]; p = 0.0004) and MAC (OR: 1.18 [95% CI: 1.06 to 1.32]; p = 0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95% CI: 0.15 to 0.38]; p < 0.0001) and MAC (risk difference = 0.20 [95% CI: 0.03 to 0.37]; p = 0.02). During follow-up (mean 2.4 +/- 0.9 years), 153 subjects (4%) developed AVC, and 198 (5%) developed MAC. The %PredLVM was associated with incident AVC (OR: 1.24 [95% CI: 1.04 to 1.47]; p = 0.02) and MAC (OR: 1.18 [95% CI: 1.01 to 1.40]; p = 0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification.
CONCLUSIONS Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders. (J Am Coll Cardiol Img 2012; 5: 781-8) (C) 2012 by the American College of Cardiology Foundation
C1 [Elmariah, Sammy] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA.
[Elmariah, Sammy; Fuster, Valentin; Halperin, Jonathan L.] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.
[Delaney, Joseph A. C.] Univ Florida, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
[Budoff, Matthew J.] Harbor UCLA, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA USA.
[O'Brien, Kevin D.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Fuster, Valentin] CNIC, Madrid, Spain.
[Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Elmariah, S (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, 55 Fruit St,GRB 800, Boston, MA 02114 USA.
EM selmariah@partners.org
RI Fuster, Valentin/H-4319-2015;
OI Fuster, Valentin/0000-0002-9043-9986; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute at the National Institutes of
Health [R01 HL071739, T32 HL007824, N01-HC-95159, N01-HC-95165,
N01-HC-95169]; GlaxoSmithKline Research and Education Foundation for
Cardiovascular Disease International Competitive Grants Award Program
for Young Investigators; BG Medicine; Astellas Pharma; Bayer AG
Healthcare; Bristol-Myers Squibb/Sanofi Partnership;
Boehringer-Ingelheim; Daiichi Sankyo; Johnson Johnson; Sanofi-Aventis;
Biotronik
FX This work was supported by the National Heart, Lung, and Blood Institute
at the National Institutes of Health (Grants R01 HL071739 [to Dr.
Budoff] and T32 HL007824 [to Dr. Elmariah] and by contracts N01-HC-95159
through N01-HC-95165 and N01-HC-95169) and the GlaxoSmithKline Research
and Education Foundation for Cardiovascular Disease International
Competitive Grants Award Program for Young Investigators (to Dr.
Elmariah). Dr. Budoff has a modest consulting agreement with the General
Electric Company. Dr. O'Brien receives speaker honoraria from
AstraZeneca and Merck. Dr. Fuster chairs the HRP study, which is funded
by BG Medicine. Dr. Halperin receives consulting fees from Astellas
Pharma, Bayer AG Healthcare, the Bristol-Myers Squibb/Sanofi
Partnership, Boehringer-Ingelheim, Daiichi Sankyo, Johnson & Johnson,
and Sanofi-Aventis; honoraria from Genzyme and Portola Pharmaceuticals;
and is co-chairman of the IMPACT trial, which is sponsored by Biotronik.
All other authors have reported that they have no relationships relevant
to the contents of this paper to disclose. H. William Strauss, MD,
served as Guest Editor for this paper.
NR 27
TC 7
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD AUG
PY 2012
VL 5
IS 8
BP 781
EP 788
DI 10.1016/j.jcmg.2011.12.025
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 003DN
UT WOS:000308588500003
PM 22897991
ER
PT J
AU Armstrong, AC
Gidding, S
Gjesdal, O
Wu, C
Bluemke, DA
Lima, JAC
AF Armstrong, Anderson C.
Gidding, Samuel
Gjesdal, Ola
Wu, Colin
Bluemke, David A.
Lima, Joao A. C.
TI LV Mass Assessed by Echocardiography and CMR, Cardiovascular Outcomes,
and Medical Practice
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac magnetic resonance; cardiovascular events; echocardiography;
LVH; LVM
ID LEFT-VENTRICULAR MASS; CARDIAC MAGNETIC-RESONANCE; TIME 3-DIMENSIONAL
ECHOCARDIOGRAPHY; POPULATION-ATTRIBUTABLE RISK; CORONARY-ARTERY-DISEASE;
SOCIETY-OF-CARDIOLOGY; LEFT ATRIAL SIZE; BODY-SIZE; COMPUTED-TOMOGRAPHY;
SYSTOLIC FUNCTION
AB The authors investigated 3 important areas related to the clinical use of left ventricular mass (LVM): accuracy of assessments by echocardiography and cardiac magnetic resonance (CMR), the ability to predict cardiovascular outcomes, and the comparative value of different indexing methods. The recommended formula for echocardiographic estimation of LVM uses linear measurements and is based on the assumption of the left ventricle (LV) as a prolate ellipsoid of revolution. CMR permits a modeling of the LV free of cardiac geometric assumptions or acoustic window dependency, showing better accuracy and reproducibility. However, echocardiography has lower cost, easier availability, and better tolerability. From the MEDLINE database, 26 longitudinal echocardiographic studies and 5 CMR studies investigating LVM or LV hypertrophy as predictors of death or major cardiovascular outcomes were identified. LVM and LV hypertrophy were reliable cardiovascular risk predictors using both modalities. However, no study directly compared the methods for the ability to predict events, agreement in hypertrophy classification, or performance in cardiovascular risk reclassification. Indexing LVM to body surface area was the earliest normalization process used, but it seems to underestimate the prevalence of hypertrophy in obese and overweight subjects. Dividing LVM by height to the allometric power of 1.7 or 2.7 is the most promising normalization method in terms of practicality and usefulness from a clinical and scientific standpoint for scaling myocardial mass to body size. The measurement of LVM, calculation of LVM index, and classification for LV hypertrophy should be standardized by scientific societies across measurement techniques and adopted by clinicians in risk stratification and therapeutic decision making. (J Am Coll Cardiol Img 2012; 5: 837-48) (C) 2012 by the American College of Cardiology Foundation
C1 [Armstrong, Anderson C.; Gjesdal, Ola; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21287 USA.
[Armstrong, Anderson C.] Univ Fed Vale Sao Francisco, Sch Med, Petrolina, Brazil.
[Gidding, Samuel] Alfred I duPont Hosp Children, Nemours Cardiac Ctr, Wilmington, DE USA.
[Wu, Colin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Div Cardiol, 600 N Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Armstrong, Anderson/G-8407-2012;
OI Armstrong, Anderson/0000-0003-3161-8922; Gjesdal,
Ola/0000-0003-1913-6445; Bluemke, David/0000-0002-8323-8086
FU Universidade Federal do Vale do Sao Francisco (UNIVASF)
FX Dr. Armstrong was funded by Universidade Federal do Vale do Sao
Francisco (UNIVASF). All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
NR 87
TC 72
Z9 75
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD AUG
PY 2012
VL 5
IS 8
BP 837
EP 848
DI 10.1016/j.jcmg.2012.06.003
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 003DN
UT WOS:000308588500010
PM 22897998
ER
PT J
AU Levy, G
Hill, MJ
Beall, S
Zarek, SM
Segars, JH
Catherino, WH
AF Levy, Gary
Hill, Micah J.
Beall, Stephanie
Zarek, Shvetha M.
Segars, James H.
Catherino, William H.
TI Leiomyoma: genetics, assisted reproduction, pregnancy and therapeutic
advances
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Review
DE Assisted reproductive technologies; Leiomyoma genetics; Leiomyoma
ID UTERINE-ARTERY EMBOLIZATION; ESTROGEN-RECEPTOR-ALPHA; IN-VITRO
FERTILIZATION; RANDOMIZED CONTROLLED-TRIAL; ADVERSE OBSTETRIC OUTCOMES;
PLACEBO-CONTROLLED TRIAL; LOW-DOSE MIFEPRISTONE; LAPAROSCOPIC
MYOMECTOMY; ABDOMINAL MYOMECTOMY; EXTRACELLULAR-MATRIX
AB Uterine leiomyomas are common, benign, reproductive tract tumors affecting a majority of reproductive aged women. They are associated with gynecologic morbidity and detrimentally affect reproductive potential. The etiology of leiomyomas is poorly understood and their diagnosis prior to treatment with Assisted Reproductive Technologies (ART) represents a management dilemma. The purpose of this paper is to review known genetic and molecular contributions to the etiologies of leiomyomas, describe their impact on ART outcomes and reproductive potential, and review alternative therapies and future directions in management.
A critical review of the literature pertaining to genetic component of uterine leiomyomas, their impact on ART and pregnancy and leiomyoma therapeutics was performed.
Uterine leiomyomas are characterized by complex molecular mechanisms. Their location and size determines their potential detriment to ART and reproductive function and novel therapeutic modalities are being developed.
The high prevalence of uterine leiomyomas and their potential detrimental influence on ART and reproductive function warrants continued well-designed studies to ascertain their etiology, optimal treatment and novel less morbid therapies.
C1 [Levy, Gary; Hill, Micah J.; Beall, Stephanie; Zarek, Shvetha M.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Levy, Gary; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
RP Levy, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
EM gary.levy@nih.gov
NR 128
TC 23
Z9 27
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD AUG
PY 2012
VL 29
IS 8
BP 703
EP 712
DI 10.1007/s10815-012-9784-0
PG 10
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA 997RX
UT WOS:000308184900002
PM 22584729
ER
PT J
AU Carter, TC
Kay, DM
Browne, ML
Liu, AY
Romitti, PA
Kuehn, D
Conley, MR
Caggana, M
Druschel, CM
Brody, LC
Mills, JL
AF Carter, Tonia C.
Kay, Denise M.
Browne, Marilyn L.
Liu, Aiyi
Romitti, Paul A.
Kuehn, Devon
Conley, Mary R.
Caggana, Michele
Druschel, Charlotte M.
Brody, Lawrence C.
Mills, James L.
TI Hirschsprung's disease and variants in genes that regulate enteric
neural crest cell proliferation, migration and differentiation
SO JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE congenital abnormalities; enteric nervous system; Hirschsprung disease;
RET
ID RET PROTOONCOGENE; TYROSINE KINASE; MUTATIONS; COMMON; ASSOCIATION;
EXPRESSION; TRANSCRIPTION; NEUROBLASTS; POPULATION; HAPLOTYPES
AB Hirschsprung's disease (HSCR) results from failed colonization of the embryonic gut by enteric neural crest cells (ENCCs); colonization requires RET proto-oncogene (RET) signaling. We sequenced RET to identify coding and splice-site variants in a population-based case group and we tested for associations between HSCR and common variants in RET and candidate genes (ASCL1, homeobox B5 (HOXB5), L1 cell adhesion molecule (L1CAM), paired-like homeobox 2b (PHOX2B), PROK1 and PROKR1) chosen because they are involved in ENCC proliferation, migration and differentiation in animal models. We conducted a nested case-control study of 304 HSCR cases and 1215 controls. Among 38 (12.5%) cases with 34 RET coding and splice-site variants, 18 variants were previously unreported. We confirmed associations with common variants in HOXB5 and PHOX2B but the associations with variants in ASCL1, L1CAM and PROK1 were not significant after multiple comparisons adjustment. RET variants were strongly associated with HSCR (P-values between 10(-3) and 10(-31)) but this differed by race/ethnicity: associations were absent in African-Americans. Our population-based study not only identified novel RET variants in HSCR cases, it showed that common RET variants may not contribute to HSCR in all race/ethnic groups. The findings for HOXB5 and PHOX2B provide supportive evidence that genes regulating ENCC proliferation, migration and differentiation could be risk factors for HSCR. Journal of Human Genetics (2012) 57, 485-493; doi: 10.1038/jhg.2012.54; published online 31 May 2012
C1 [Carter, Tonia C.; Liu, Aiyi; Kuehn, Devon; Conley, Mary R.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Kay, Denise M.; Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY USA.
[Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA.
[Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA.
[Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Mills, JL (reprint author), NICHD, DESPR, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
OI Kay, Denise/0000-0002-9928-2698; Liu, Aiyi/0000-0002-6618-5082
FU National Heart, Lung and Blood Institute GO Exome Sequencing Project;
Lung GO Sequencing Project [HL-102923]; WHI Sequencing Project
[HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO
Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010];
Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[HHSN267200703431C, N01-DK-7-3431]
FX We are grateful to April J Atkins, Robert J Sicko, Emily C McGrath and
Salvatore Duva for laboratory and technical assistance, and to Sandra D
Richardson for data management support. We thank the National Heart,
Lung and Blood Institute GO Exome Sequencing Project and its ongoing
studies that produced and provided exome variant calls for comparison:
the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project
(HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO
Sequencing Project (HL-102926) and the Heart GO Sequencing Project
(HL-103010). 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 (contract no.
HHSN267200703431C; NICHD no. N01-DK-7-3431).
NR 45
TC 8
Z9 12
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1434-5161
J9 J HUM GENET
JI J. Hum. Genet.
PD AUG
PY 2012
VL 57
IS 8
BP 485
EP 493
DI 10.1038/jhg.2012.54
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 996EG
UT WOS:000308066700004
PM 22648184
ER
PT J
AU Koola, MM
McMahon, RP
Wehring, HJ
Liu, F
Mackowick, KM
Warren, KR
Feldman, S
Shim, JC
Love, RC
Kelly, DL
AF Koola, Maju Mathew
McMahon, Robert P.
Wehring, Heidi J.
Liu, Fang
Mackowick, Kristen M.
Warren, Kimberly R.
Feldman, Stephanie
Shim, Joo-Cheol
Love, Raymond C.
Kelly, Deanna L.
TI Alcohol and cannabis use and mortality in people with schizophrenia and
related psychotic disorders
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Psychotic disorders; Substance use; Cannabis; Alcohol; Mortality
ID CARDIOVASCULAR-DISEASE MORTALITY; SUBSTANCE USE DISORDERS; 5-YEAR
FOLLOW-UP; MENTAL-DISORDERS; DRUG-ABUSE; ENDOCANNABINOID SYSTEM;
MULTIPLE-SCLEROSIS; MEDICAL MARIJUANA; DRINKING PATTERN; PREVALENCE
AB The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use. We examined the rate of substance use and the risk of substance use on mortality risk over a 4-10 year period in 762 people with psychotic disorders. Deceased patients were identified from the Social Security Death Index and the Maryland Division of Vital Records. Substance use was defined as regular and heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime substance use, with co-morbid cannabis and alcohol use occurring most commonly. Out of 762 subjects, 62 died during follow up. In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model. Alcohol use was not predictive of mortality. We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments. Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Koola, Maju Mathew; McMahon, Robert P.; Wehring, Heidi J.; Liu, Fang; Warren, Kimberly R.; Feldman, Stephanie; Love, Raymond C.; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat,Treatment Res Program, Baltimore, MD 21228 USA.
[Mackowick, Kristen M.] Natl Inst Drug Abuse, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Shim, Joo-Cheol] Inje Univ, Busan Paik Hosp, Clin Trial Ctr, Pusan, South Korea.
[Shim, Joo-Cheol] Inje Univ, Busan Paik Hosp, Dept Psychiat, Pusan, South Korea.
[Love, Raymond C.] Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA.
RP Koola, MM (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat,Treatment Res Program, 55 Wade Ave,Tawes Bldg, Baltimore, MD 21228 USA.
RI McMahon, Robert/C-5462-2009
FU National Institute of Mental Health [R03 MH076985-01]; NIMH
[MH067533-07]; Bristol-Myers Squibb; Janssen Pharmaceutica
FX The National Institute of Mental Health (R03 MH076985-01; Kelly, PI)
supported this study. The first author's manuscript preparation was
supported by the NIMH funded T32 grant (MH067533-07; Carpenter, PI).;
Dr. Kelly has received grant support from Bristol-Myers Squibb and
Janssen Pharmaceutica. All other authors declare that they have no
conflicts of interest.
NR 64
TC 11
Z9 11
U1 3
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD AUG
PY 2012
VL 46
IS 8
BP 987
EP 993
DI 10.1016/j.jpsychires.2012.04.019
PG 7
WC Psychiatry
SC Psychiatry
GA 980AF
UT WOS:000306865300003
PM 22595870
ER
PT J
AU Gundry, RL
Riordon, DR
Tarasova, Y
Chuppa, S
Bhattacharya, S
Juhasz, O
Wiedemeier, O
Milanovich, S
Noto, FK
Tchernyshyov, I
Raginski, K
Bausch-Fluck, D
Tae, HJ
Marshall, S
Duncan, SA
Wollscheid, B
Wersto, RP
Rao, S
Van Eyk, JE
Boheler, KR
AF Gundry, Rebekah L.
Riordon, Daniel R.
Tarasova, Yelena
Chuppa, Sandra
Bhattacharya, Subarna
Juhasz, Ondrej
Wiedemeier, Olena
Milanovich, Samuel
Noto, Fallon K.
Tchernyshyov, Irina
Raginski, Kimberly
Bausch-Fluck, Damaris
Tae, Hyun-Jin
Marshall, Shannon
Duncan, Stephen A.
Wollscheid, Bernd
Wersto, Robert P.
Rao, Sridhar
Van Eyk, Jennifer E.
Boheler, Kenneth R.
TI A Cell Surfaceome Map for Immunophenotyping and Sorting Pluripotent Stem
Cells
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID PLASMA-MEMBRANE PROTEOMICS; EMBRYONAL CARCINOMA-CELLS; HEMATOPOIETIC
STEM; ADHESION MOLECULE; STATISTICAL-MODEL; MASS-SPECTROMETRY; CD133
PROTEIN; MOUSE; DIFFERENTIATION; IDENTIFICATION
AB Induction of a pluripotent state in somatic cells through nuclear reprogramming has ushered in a new era of regenerative medicine. Heterogeneity and varied differentiation potentials among induced pluripotent stem cell (iPSC) lines are, however, complicating factors that limit their usefulness for disease modeling, drug discovery, and patient therapies. Thus, there is an urgent need to develop nonmutagenic rapid throughput methods capable of distinguishing among putative iPSC lines of variable quality. To address this issue, we have applied a highly specific chemoproteomic targeting strategy for de novo discovery of cell surface N-glycoproteins to increase the knowledge-base of surface exposed proteins and accessible epitopes of pluripotent stem cells. We report the identification of 500 cell surface proteins on four embryonic stem cell and iPSCs lines and demonstrate the biological significance of this resource on mouse fibroblasts containing an oct4-GFP expression cassette that is active in reprogrammed cells. These results together with immunophenotyping, cell sorting, and functional analyses demonstrate that these newly identified surface marker panels are useful for isolating iPSCs from heterogeneous reprogrammed cultures and for isolating functionally distinct stem cell subpopulations. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.018135, 303-316, 2012.
C1 [Gundry, Rebekah L.; Chuppa, Sandra; Bhattacharya, Subarna; Wiedemeier, Olena] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
[Gundry, Rebekah L.; Chuppa, Sandra; Bhattacharya, Subarna; Wiedemeier, Olena] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, Milwaukee, WI 53226 USA.
[Noto, Fallon K.; Duncan, Stephen A.; Rao, Sridhar] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
[Milanovich, Samuel; Rao, Sridhar] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Gundry, Rebekah L.; Riordon, Daniel R.; Tarasova, Yelena; Juhasz, Ondrej; Raginski, Kimberly; Tae, Hyun-Jin; Marshall, Shannon; Wersto, Robert P.; Boheler, Kenneth R.] NIA, NIH, Baltimore, MD 21224 USA.
[Gundry, Rebekah L.; Tarasova, Yelena; Tchernyshyov, Irina; Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21224 USA.
[Milanovich, Samuel; Rao, Sridhar] Blood Res Inst, Milwaukee, WI 53226 USA.
[Bausch-Fluck, Damaris; Wollscheid, Bernd] Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland.
[Bausch-Fluck, Damaris; Wollscheid, Bernd] Univ Zurich UZH, NCCR, Neuro Ctr Prote, CH-8093 Zurich, Switzerland.
[Bausch-Fluck, Damaris; Wollscheid, Bernd] Swiss Fed Inst Technol, CH-8093 Zurich, Switzerland.
[Boheler, Kenneth R.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Hong Kong, Hong Kong, Peoples R China.
RP Gundry, RL (reprint author), Med Coll Wisconsin, Dept Biochem, Basic Sci Bldg 373,8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM rgundry@mcw.edu; bohelerk@grc.nia.nih.gov
RI Wollscheid, Bernd/E-8909-2010;
OI Wollscheid, Bernd/0000-0002-3923-1610; Duncan,
Stephen/0000-0002-2507-7827
FU National Institutes of Health (NIH) [K99-L094708-01/4R00HL094708-03]; BD
Biosciences Research Grant Award; Innovation Center at the Medical
College of Wisconsin; NIH/NIA; NIH Induced Pluripotent Stem Cell
Center/Center for Regenerative Medicine Research Study Award; Research
Grants Council of Hong Kong [T13-706]; NIH [5R01HL085434-02,
5K08HL87951, 1F31AA019874-01, HL089471, DK55743, HL107434]; AHA; Blood
Center Research Foundation; National Center of Competence in Research
Neural Plasticity and Repair
FX This work was supported by National Institutes of Health (NIH) grant
K99-L094708-01/4R00HL094708-03, BD Biosciences Research Grant Award, the
Innovation Center at the Medical College of Wisconsin (RLG); the
Intramural Research Program of the NIH/NIA, NIH Induced Pluripotent Stem
Cell Center/Center for Regenerative Medicine Research Study Award and
Research Grants Council of Hong Kong (Theme-based Research Scheme
T13-706) (KRB); NIH 5R01HL085434-02, AHA grant in aid (JEV); NIH
5K08HL87951, Blood Center Research Foundation (SR); NIH 1F31AA019874-01
(FN); NIH HL089471, NIH DK55743, NIH HL107434 (SAD); and National Center
of Competence in Research Neural Plasticity and Repair (BW). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 66
TC 24
Z9 24
U1 3
U2 35
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD AUG
PY 2012
VL 11
IS 8
BP 303
EP 316
DI 10.1074/mcp.M112.018135
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 995PW
UT WOS:000308024200007
PM 22493178
ER
PT J
AU Bermudez, J
Rodriguez, M
Hasegawa, M
Gonzalez-Mujica, F
Duque, S
Ito, Y
AF Bermudez, Jairo
Rodriguez, Maria
Hasegawa, Masahisa
Gonzalez-Mujica, Freddy
Duque, Sandra
Ito, Yoichiro
TI (6R,9S)-6 ''-(4 ''-Hydroxybenzoyl)-Roseoside, a New Megastigmane
Derivative from Ouratea polyantha and its Effect on Hepatic
Glucose-6-phosphatase
SO NATURAL PRODUCT COMMUNICATIONS
LA English
DT Article
DE Agathisflavone; Countercurrent chromatography; Glucose-6-phosphatase;
Megastigmanes; Ouratea polyantha; Terpenes; (6R,9S)-6 '-(4
''-Hydroxybenzoyl)-roseoside
ID MICROSOMAL GLUCOSE-6-PHOSPHATASE; SYSTEM; BIFLAVONOIDS; SEMISERRATA
AB A new megastigmane derivative, (6R,98)-6'-(4 ''-hydroxybenzoyl)-roseoside (1) and two known compounds, the biflavoneagathisflavone (2) and 4-hydroxybenzoic acid (3) were isolated and purified from leaves and stems of Ouratea polyantha Engl. Agathisflavone was isolated in a single high-speed countercurrent chromatography run, while the megastigmane was purified in two steps, by using a combination of high-speed countercurrent chromatography and analytical column chromatography. All structures were elucidated on the basis of spectral evidence and comparison with literature data. Compound 1 was characterized by (4)20, UV-Vis, IR, MS, H-1 NMR, C-13 NMR, HMQC, HMBC, COSY and NOESY. Compounds 1 and 2 showed an inhibitory effect of 63.6 and 13.7% on the G-6-Pase intact microsomes, respectively.
C1 [Bermudez, Jairo; Rodriguez, Maria; Hasegawa, Masahisa] Cent Univ Venezuela, Fac Ciencias, Escuela Quim, Lab Prod Nat, Caracas, Venezuela.
[Bermudez, Jairo; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Gonzalez-Mujica, Freddy; Duque, Sandra] Cent Univ Venezuela, Fac Med, Inst Med Expt, Secc Bioquim Med, Caracas, Venezuela.
RP Rodriguez, M (reprint author), Cent Univ Venezuela, Fac Ciencias, Escuela Quim, Lab Prod Nat, Apartado Postal 47102, Caracas, Venezuela.
EM mariac.rodriguez@ciens.ucv.ve
FU Consejo de Desarrollo Cientifico y Humanistico de la Universidad Central
de Venezuela [PG.03.7345.2008, PI-09-7645-09/1]
FX This work was supported by Grant PG.03.7345.2008 and PI-09-7645-09/1
from the Consejo de Desarrollo Cientifico y Humanistico de la
Universidad Central de Venezuela.
NR 24
TC 3
Z9 3
U1 0
U2 5
PU NATURAL PRODUCTS INC
PI WESTERVILLE
PA 7963 ANDERSON PARK LN, WESTERVILLE, OH 43081 USA
SN 1934-578X
EI 1555-9475
J9 NAT PROD COMMUN
JI Nat. Prod. Commun.
PD AUG
PY 2012
VL 7
IS 8
BP 973
EP 976
PG 4
WC Chemistry, Medicinal; Food Science & Technology
SC Pharmacology & Pharmacy; Food Science & Technology
GA 996CF
UT WOS:000308060900002
PM 22978207
ER
PT J
AU Zou, WP
Restifo, NP
AF Zou, Weiping
Restifo, Nicholas P.
TI Nine lives for T(H)9s?
SO NATURE MEDICINE
LA English
DT Editorial Material
ID TH17 CELLS; T-CELLS; TUMOR; DIFFERENTIATION; IMMUNOTHERAPY; RELEVANCE;
CANCER; BETA
AB There is currently much interest in dissecting the mechanisms of tumor immunity. A new study shows that a subset of CD4(+) T cells that produce the cytokine interleukin-9 (IL-9) mediate inhibition of melanoma growth in mice and that analogous IL-9-producing T cells are present in human skin (pages 1248-1253). Could such cells be manipulated to develop new therapeutic strategies for melanoma?
C1 [Zou, Weiping] Univ Michigan, Dept Surg, Grad Program Immunol, Ann Arbor, MI 48109 USA.
[Zou, Weiping] Univ Michigan, Dept Surg, Grad Program Tumor Biol, Ann Arbor, MI 48109 USA.
[Zou, Weiping] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA.
RP Zou, WP (reprint author), Univ Michigan, Dept Surg, Grad Program Immunol, Ann Arbor, MI 48109 USA.
EM wzou@med.umich.edu; restifo@nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
NR 16
TC 1
Z9 1
U1 1
U2 9
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 AUG
PY 2012
VL 18
IS 8
BP 1177
EP 1178
DI 10.1038/nm.2868
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 988DU
UT WOS:000307469300015
PM 22869182
ER
PT J
AU Gembarska, A
Luciani, F
Fedele, C
Russell, EA
Dewaele, M
Villar, S
Zwolinska, A
Haupt, S
de Lange, J
Yip, D
Goydos, J
Haigh, JJ
Haupt, Y
Larue, L
Jochemsen, A
Shi, HB
Moriceau, G
Lo, RS
Ghanem, G
Shackleton, M
Bernal, F
Marine, JC
AF Gembarska, Agnieszka
Luciani, Flavie
Fedele, Clare
Russell, Elisabeth A.
Dewaele, Michael
Villar, Stephanie
Zwolinska, Aleksandra
Haupt, Sue
de Lange, Job
Yip, Dana
Goydos, James
Haigh, Jody J.
Haupt, Ygal
Larue, Lionel
Jochemsen, Aart
Shi, Hubing
Moriceau, Gatien
Lo, Roger S.
Ghanem, Ghanem
Shackleton, Mark
Bernal, Federico
Marine, Jean-Christophe
TI MDM4 is a key therapeutic target in cutaneous melanoma
SO NATURE MEDICINE
LA English
DT Article
ID TUMOR-SUPPRESSOR ACTIVITY; IN-VIVO; MALIGNANT-MELANOMA; P53 PATHWAY;
N-RAS; METASTATIC MELANOMA; BREAST-CANCER; STAPLED P53; CELL-DEATH; BRAF
AB The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in TP53 (encoding tumor protein 53) is a common step in human cancer. However, in melanoma-a highly chemotherapy-resistant disease-TP53 mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppression. Here we show that Mdm4 p53 binding protein homolog (MDM4), a negative regulator of p53, is upregulated in a substantial proportion (similar to 65%) of stage I-IV human melanomas and that melanocyte-specific Mdm4 overexpression enhanced tumorigenesis in a mouse model of melanoma induced by the oncogene Nras. MDM4 promotes the survival of human metastatic melanoma by antagonizing p53 proapoptotic function. Notably, inhibition of the MDM4-p53 interaction restored p53 function in melanoma cells, resulting in increased sensitivity to cytotoxic chemotherapy and to inhibitors of the BRAF (V600E) oncogene. Our results identify MDM4 as a key determinant of impaired p53 function in human melanoma and designate MDM4 as a promising target for antimelanoma combination therapy.
C1 [Gembarska, Agnieszka; Luciani, Flavie; Dewaele, Michael; Zwolinska, Aleksandra; Marine, Jean-Christophe] VIB, Lab Mol Canc Biol, Ctr Biol Dis, Louvain, Belgium.
[Gembarska, Agnieszka; Luciani, Flavie; Dewaele, Michael; Zwolinska, Aleksandra; Marine, Jean-Christophe] Katholieke Univ KU Leuven, Ctr Human Genet, Louvain, Belgium.
[Fedele, Clare; Shackleton, Mark] Peter MacCallum Canc Ctr, Melanoma Res Lab, Melbourne, Australia.
[Fedele, Clare; Shackleton, Mark] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Russell, Elisabeth A.; Bernal, Federico] NCI, Metab Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Villar, Stephanie] Int Agcy Res Canc IARC CIRC, Lyon, France.
[Haupt, Sue; Haupt, Ygal; Shackleton, Mark] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
[Haupt, Sue; Haupt, Ygal] Peter MacCallum Canc Ctr, Div Res, Melbourne, Australia.
[Jochemsen, Aart] Univ Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands.
[Yip, Dana; Goydos, James] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
[Haigh, Jody J.] VIB, Dept Mol Biomed Res, Vasc Cell Biol Unit, Ghent, Belgium.
[Haigh, Jody J.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium.
[Haupt, Ygal] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
[Larue, Lionel] CNRS, INSERM, U1021, Inst Curie,UMR3347, F-91405 Orsay, France.
[Shi, Hubing; Moriceau, Gatien; Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Dept Med,Div Dermatol, Los Angeles, CA 90095 USA.
[Shi, Hubing; Moriceau, Gatien; Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Ghanem, Ghanem] Inst Jules Bordet, B-1000 Brussels, Belgium.
RP Marine, JC (reprint author), VIB, Lab Mol Canc Biol, Ctr Biol Dis, Louvain, Belgium.
EM jeanchristophe.marine@cme.vib-kuleuven.be
RI Larue, Lionel/F-7355-2013; Shi, Hubing/B-8445-2014; Marine, Jean
Christophe/J-2237-2015; Marine, Jean-Christophe/K-3292-2016; Larue,
Lionel/I-6532-2016;
OI Marine, Jean-Christophe/0000-0003-2433-9837; Shi,
Hubing/0000-0002-2926-3440; de Lange, Job/0000-0002-9002-8829
FU 'Het Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO)' scholarship;
Clare Oliver Memorial Fellowship from the Victorian Cancer Agency;
Pfizer Australia; Victorian Endowment for Science, Knowledge and
Innovation (VESKI); Australian National Health and Medical Research
Council [509197, 1026990, 628426]; Stand Up to Cancer; Joint Center for
Translational Medicine; Eli and Edythe Broad Center of Regenerative
Medicine and Stem Cell Research; Seaver Institute; US National
Institutes of Health; National Cancer Institute; Association for
International Cancer Research (AICR); Melbourne Melanoma Project;
Victorian Cancer Agency; Belgian Foundation against Cancer
FX We thank O.Van Goethem for excellent technical assistance. We thank P.
Agostinis, P. Wolter and M. Skipper for helpful discussions and comments
on the manuscript. We thank M. Cario-Andre and A. Taied for materials
from human nevi. A. Zwolinska is a recipient of a 'Het Fonds
Wetenschappelijk Onderzoek-Vlaanderen (FWO)' scholarship. C. Fedele was
supported by a Clare Oliver Memorial Fellowship from the Victorian
Cancer Agency. M. Shackleton was supported by fellowships from Pfizer
Australia and the Victorian Endowment for Science, Knowledge and
Innovation (VESKI). Y. and S. Haupt were supported by the Australian
National Health and Medical Research Council (nos. 509197, 1026990 and
628426) and VESKI. R.S. Lo was supported by Stand Up to Cancer, the
Joint Center for Translational Medicine, the Eli and Edythe Broad Center
of Regenerative Medicine and Stem Cell Research, and the Seaver
Institute. This work was supported by the Intramural Research Program of
the US National Institutes of Health and the National Cancer Institute,
the Association for International Cancer Research (AICR), the Melbourne
Melanoma Project, the Victorian Cancer Agency and the 'Belgian
Foundation against Cancer'.
NR 53
TC 111
Z9 113
U1 3
U2 44
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 AUG
PY 2012
VL 18
IS 8
BP 1239
EP +
DI 10.1038/nm.2863
PG 24
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 988DU
UT WOS:000307469300030
PM 22820643
ER
PT J
AU Purwar, R
Schlapbach, C
Xiao, S
Kang, HS
Elyaman, W
Jiang, XD
Jetten, AM
Khoury, SJ
Fuhlbrigge, RC
Kuchroo, VK
Clark, RA
Kupper, TS
AF Purwar, Rahul
Schlapbach, Christoph
Xiao, Sheng
Kang, Hong Soon
Elyaman, Wassim
Jiang, Xiaodong
Jetten, Anton M.
Khoury, Samia J.
Fuhlbrigge, Robert C.
Kuchroo, Vijay K.
Clark, Rachael A.
Kupper, Thomas S.
TI Robust tumor immunity to melanoma mediated by interleukin-9-producing T
cells
SO NATURE MEDICINE
LA English
DT Article
ID LARGE ESTABLISHED MELANOMA; IN-VIVO; IFN-GAMMA; ANTITUMOR RESPONSES;
IL-9 PRODUCTION; T(H)17 CELLS; ROR-GAMMA; TGF-BETA; DIFFERENTIATION;
GROWTH
AB Interleukin-9 (IL-9) is a T cell cytokine that acts through a gamma C-family receptor on target cells and is associated with inflammation and allergy. We determined that T cells from mice deficient in the T helper type 17 (T(H)17) pathway genes encoding retinoid-related orphan receptor gamma (ROR-gamma) and IL-23 receptor (IL-23R) produced abundant IL-9, and we found substantial growth inhibition of B16F10 melanoma in these mice. IL-9-blocking antibodies reversed this tumor growth inhibition and enhanced tumor growth in wild-type (WT) mice. Il9r(-/-) mice showed accelerated tumor growth, and administration of recombinant IL-9 (rIL-9) to tumor-bearing WT and Rag1(-/-) mice inhibited melanoma as well as lung carcinoma growth. Adoptive transfer of tumor-antigen-specific T(H)9 cells into both WT and Rag1(-/-) mice suppressed melanoma growth; this effect was abrogated by treatment with neutralizing antibodies to IL-9. Exogenous rIL-9 inhibited tumor growth in Rag1(-/-) mice but not in mast-cell-deficient mice, suggesting that the targets of IL-9 in this setting include mast cells but not T or B cells. In addition, we found higher numbers of T(H)9 cells in normal human skin and blood compared to metastatic lesions of subjects with progressive stage IV melanoma. These results suggest a role for IL-9 in tumor immunity and offer insight into potential therapeutic strategies.
C1 [Purwar, Rahul; Schlapbach, Christoph; Jiang, Xiaodong; Fuhlbrigge, Robert C.; Clark, Rachael A.; Kupper, Thomas S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Xiao, Sheng; Elyaman, Wassim; Khoury, Samia J.; Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Kang, Hong Soon; Jetten, Anton M.] NIEHS, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Kupper, TS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
EM tkupper@partners.org
RI Schlapbach, Christoph/D-5832-2013;
OI Schlapbach, Christoph/0000-0003-0258-1243; Jetten,
Anton/0000-0003-0954-4445; khoury, samia/0000-0003-3198-6063
FU US National Institutes of Health [R01 AI-041707, R01 AI-097128, P50
CA-093683, R01-AR-056720, R03-MH-095529, Z01-ES-101586]; Skin Cancer
Foundation; Swiss National Science Foundation; Foundation Rene Touraine;
Damon Runyon Clinical Investigator Award
FX This research was supported by grants from US National Institutes of
Health to T.S.K. (R01 AI-041707, R01 AI-097128 and P50 CA-093683),
R.A.C. (R01-AR-056720 and R03-MH-095529) and A.M.J. (Z01-ES-101586).
R.P. received a Research Grant Award from The Skin Cancer Foundation.
The authors thank K. Gerrish (US National Institutes of Health) with his
help with the microarray analysis. J.-C. Renauld39 (Ludwig
Institute, Belgium) provided Il9r-/- mice and the
corresponding control mice (Il9r+/-). Neutralizing antibodies
to IL-9 (MM9C1) were a kind gift from J.v. Snick (Ludwig Institute,
Belgium). Salary support for C.S. was provided by the Swiss National
Science Foundation and the Foundation Rene Touraine and for R.A.C. from
a Damon Runyon Clinical Investigator Award.
NR 39
TC 93
Z9 97
U1 5
U2 24
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 AUG
PY 2012
VL 18
IS 8
BP 1248
EP +
DI 10.1038/nm.2856
PG 15
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 988DU
UT WOS:000307469300031
PM 22772464
ER
PT J
AU Zhu, Q
Talton, J
Zhang, GF
Cunningham, T
Wang, ZJ
Waters, RC
Kirk, J
Eppler, B
Klinman, DM
Sui, YJ
Gagnon, S
Belyakov, IM
Mumper, RJ
Berzofsky, JA
AF Zhu, Qing
Talton, James
Zhang, Guofeng
Cunningham, Tshaka
Wang, Zijian
Waters, Robert C.
Kirk, James
Eppler, Baerbel
Klinman, Dennis M.
Sui, Yongjun
Gagnon, Susan
Belyakov, Igor M.
Mumper, Russell J.
Berzofsky, Jay A.
TI Large intestine-targeted, nanoparticle-releasing oral vaccine to control
genitorectal viral infection
SO NATURE MEDICINE
LA English
DT Article
ID IN-VIVO EVALUATION; T-CELL RESPONSES; DRUG-DELIVERY; PROTECTS MICE;
RECTAL MUCOSA; MACAQUES; IMMUNIZATION; HIV; COMPARTMENTALIZATION;
TECHNOLOGIES
AB Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.
C1 [Zhu, Qing; Cunningham, Tshaka; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Zhu, Qing] AF Gen Hosp, Dept Oncol, Beijing, Peoples R China.
[Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, US Natl Inst Hlth, Bethesda, MD USA.
[Wang, Zijian] Jingmeng Res Ctr, Beijing, Peoples R China.
[Klinman, Dennis M.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Belyakov, Igor M.] Univ Michigan, Sch Med, Michigan Nanotechnol Inst Med & Biol Sci, Ann Arbor, MI USA.
[Belyakov, Igor M.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Mumper, Russell J.] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC USA.
RP Zhu, Q (reprint author), NCI, Vaccine Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM qing20892@gmail.com; berzofsj@mail.nih.gov
FU Intramural Research Program of NIH; National Cancer Institute; Center
for Cancer Research; Intramural AIDS Targeted Antiviral Program;
National Natural Science Foundation of China [31170872]; Collaborative
Research and Development Agreement with Nanotherapeutics Inc
FX We thank B. Moss and P. Earl (US National Institutes of Health (NIH))
for generously providing vPE16, G. Cohen (University of Pennsylvania)
for vaccinia antibodies, the NIH Tetramer Facility for tetramer P18-I10
and BEI Resources for vaccinia recombinant proteins. We also thank J.
Hooper, D. Johnson, M. Dobrovolskaia, B. Zolnik, J. Gao and X. Liu for
professional comments and help, and J. FitzGerald for electron
microscopy. We appreciate Z. Xia, D. Pendleton, D. Li and L. Smith for
their technical and secretarial assistance. This research was supported
by the Intramural Research Program of NIH, the National Cancer
Institute, the Center for Cancer Research and the Intramural AIDS
Targeted Antiviral Program, a grant from the National Natural Science
Foundation of China (31170872), and a Collaborative Research and
Development Agreement with Nanotherapeutics Inc.
NR 32
TC 59
Z9 60
U1 7
U2 77
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 AUG
PY 2012
VL 18
IS 8
BP 1291
EP +
DI 10.1038/nm.2866
PG 22
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 988DU
UT WOS:000307469300037
PM 22797811
ER
PT J
AU Ahsan, A
Ramanand, SG
Whitehead, C
Hiniker, SM
Rehemtulla, A
Pratt, WB
Jolly, S
Gouveia, C
Truong, K
Van Waes, C
Ray, D
Lawrence, TS
Nyati, MK
AF Ahsan, Aarif
Ramanand, Susmita G.
Whitehead, Christopher
Hiniker, Susan M.
Rehemtulla, Alnawaz
Pratt, William B.
Jolly, Shruti
Gouveia, Christopher
Kristy Truong
Van Waes, Carter
Ray, Dipankar
Lawrence, Theodore S.
Nyati, Mukesh K.
TI Wild-type EGFR Is Stabilized by Direct Interaction with HSP90 in Cancer
Cells and Tumors
SO NEOPLASIA
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; MOLECULAR CHAPERONE HSP90; HEAT-SHOCK-PROTEIN;
NECK-CANCER; IN-VITRO; INHIBITOR; RADIOSENSITIZATION; GELDANAMYCIN;
EXPRESSION; CETUXIMAB
AB The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90) is known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type (WT) WT-EGFR is unclear. In this report, we demonstrate that fully mature, membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the HSP90 inhibitors geldanamycin (GA) and AT13387 cause a decrease in WT-EGFR in cultured head and neck cancer cells. This decrease results from a significantly reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft specimens after treatment with AT13387 under conditions that inhibited tumor growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR is a client protein of HSP90 and that their interaction is critical for maintaining both the stability of the receptor as well as the growth of EGFR-dependent cancers. Furthermore, these findings support the search for specific agents that disrupt HSP90's ability to act as an EGFR chaperone.
C1 [Ahsan, Aarif; Ramanand, Susmita G.; Hiniker, Susan M.; Rehemtulla, Alnawaz; Jolly, Shruti; Ray, Dipankar; Lawrence, Theodore S.; Nyati, Mukesh K.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
[Whitehead, Christopher] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Pratt, William B.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Gouveia, Christopher; Kristy Truong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
RP Nyati, MK (reprint author), Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
EM nyati@umich.edu
OI Hiniker, Susan/0000-0003-4723-2151
FU Michigan Institute for Clinical and Health Research [R01CA131290, P50
CADE97248]; University of Michigan Cancer Center [5 P30 CA46592]; James
Stuart and Barbara Padnos Research Funds for Cancer Research; NIDCD
intramural program [ZIA-DC-000073]; Alfred Taubman Scholarship
FX This work was supported by R01CA131290, P50 CADE97248, Michigan
Institute for Clinical and Health Research, University of Michigan
Cancer Center support grant 5 P30 CA46592, and the James Stuart and
Barbara Padnos Research Funds for Cancer Research (M.K. Nyati), NIDCD
intramural program project ZIA-DC-000073 (C. Van Waes), and an Alfred
Taubman Scholarship (T.S. Lawrence).
NR 37
TC 34
Z9 34
U1 0
U2 3
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD AUG
PY 2012
VL 14
IS 8
BP 670
EP +
DI 10.1593/neo.12986
PG 9
WC Oncology
SC Oncology
GA 001WJ
UT WOS:000308490500001
PM 22952420
ER
PT J
AU Woldemichael, GM
Turbyville, TJ
Vasselli, JR
Linehan, WM
McMahon, JB
AF Woldemichael, Girma M.
Turbyville, Thomas J.
Vasselli, James R.
Linehan, W. Marston
McMahon, James B.
TI Lack of a Functional VHL Gene Product Sensitizes Renal Cell Carcinoma
Cells to the Apoptotic Effects of the Protein Synthesis Inhibitor
Verrucarin A
SO NEOPLASIA
LA English
DT Article
ID STRESS GRANULES; CYTOPLASMIC LOCALIZATION; TRANSLATION; INDUCTION;
NUCLEAR; CANCER
AB Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells afforded resistance to VA's apoptotic effects. This resistance is mediated in part by the formation of stress granules that entrap signaling molecules that initiate the apoptotic signaling cascade. The VHL gene product was found to be a component of stress granules that develop as result of VA treatment. These findings reveal an important role for the VHL gene product in cytotoxic stress response and have important implications for the rational development of VA-related compounds in chemotherapeutic targeting of CCRCC.
C1 [Woldemichael, Girma M.] SAIC Frederick Inc, Basic Sci Program, Mol Targets Lab, Frederick Natl Lab, Frederick, MD 21702 USA.
[Turbyville, Thomas J.] SAIC Frederick Inc, Opt Microscopy & Anal Lab, Frederick Natl Lab, Frederick, MD 21702 USA.
[Vasselli, James R.; Linehan, W. Marston] NCI, Urol Oncol Branch, Clin Res Ctr, Bethesda, MD 20892 USA.
[McMahon, James B.] Ctr Canc Res, Frederick Natl Lab, Mol Targets Lab, Frederick, MD USA.
RP Woldemichael, GM (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Mol Targets Lab, 1050 Boyles St,Bldg 538,Room 131, Frederick, MD 21702 USA.
EM woldemichaelg@mail.nih.gov
FU Frederick National Laboratory for Cancer Research; National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of the
National Institutes of Health; Frederick National Lab, Center for Cancer
Research
FX This project has been funded in part with federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government. This research was also supported in part by the Intramural
Research Program of the National Institutes of Health, Frederick
National Lab, Center for Cancer Research.
NR 17
TC 6
Z9 6
U1 0
U2 2
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD AUG
PY 2012
VL 14
IS 8
BP 771
EP +
DI 10.1593/neo.12852
PG 9
WC Oncology
SC Oncology
GA 001WJ
UT WOS:000308490500010
PM 22952429
ER
PT J
AU Selakovic, Z
Opsenica, D
Eaton, B
Retterer, C
Bavari, S
Burnett, JC
Solaja, BA
Panchal, RG
AF Selakovic, Zivota
Opsenica, Dejan
Eaton, Brett
Retterer, Cary
Bavari, Sina
Burnett, James C.
Solaja, Bogdan A.
Panchal, Rekha G.
TI A Limited Structural Modification Results in a Significantly More
Efficacious Diazachrysene-Based Filovirus Inhibitor
SO VIRUSES-BASEL
LA English
DT Article
DE filovirus; Ebola virus; Marburg virus; antiviral; diazachrysene;
inhibitory efficacy; toxicity; small molecule
ID EBOLA-VIRUS INFECTION; MORPHOLINO OLIGOMERS; PROTECTION; PRIMATES
AB Ebola (EBOV) and Marburg (MARV) filoviruses are highly infectious pathogens causing deadly hemorrhagic fever in humans and non-human primates. Promising vaccine candidates providing immunity against filoviruses have been reported. However, the sporadic nature and swift progression of filovirus disease underlines the need for the development of small molecule therapeutics providing immediate antiviral effects. Herein we describe a brief structural exploration of two previously reported diazachrysene (DAAC)-based EBOV inhibitors. Specifically, three analogs were prepared to examine how slight substituent modifications would affect inhibitory efficacy and inhibitor-mediated toxicity during not only EBOV, but also MARV cellular infection. Of the three analogs, one was highly efficacious, providing IC50 values of 0.696 mu M +/- 0.13 mu M and 2.76 mu M +/- 0.21 mu M against EBOV and MARV infection, respectively, with little or no associated cellular toxicity. Overall, the structure-activity and structure-toxicity results from this study provide a framework for the future development of DAAC-based filovirus inhibitors that will be both active and non-toxic in vivo.
C1 [Burnett, James C.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Selakovic, Zivota; Solaja, Bogdan A.] Univ Belgrade, Belgrade 11158, Serbia.
[Opsenica, Dejan] Univ Belgrade, Inst Chem Technol & Met, Belgrade 11000, Serbia.
[Eaton, Brett; Retterer, Cary; Bavari, Sina; Panchal, Rekha G.] USA, Med Res Inst, Inst Infect Dis, Frederick, MD 21702 USA.
RP Burnett, JC (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, POB B, Frederick, MD 21702 USA.
EM zivota.selakovic@gmail.com; dopsen@chem.bg.ac.rs;
brett.eaton@amedd.army.mil; cary.retterer@amedd.army.mil;
sina.bavari@us.army.mil; burnettjames@mail.nih.gov;
bsolaja@chem.bg.ac.rs; rekha.panchal@us.army.mil
OI Solaja, Bogdan/0000-0002-9975-2725
FU Joint Science and Technology Office [TMTI_00048_RD_T]; Ministry of
Science and Technological Development of Serbia [172008]; Frederick
National Laboratory for Cancer Research, National Institutes of Health
(US) [HHSN261200800001E]
FX This research was sponsored by the Joint Science and Technology Office
(project designation: TMTI_00048_RD_T) and the Ministry of Science and
Technological Development of Serbia (grant No. 172008). Furthermore, for
J.C.B., in compliance with SAIC-Frederick, Inc. contractual
requirements: this project has been funded in whole or in part with
federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health (US), under Contract No.
HHSN261200800001E.
NR 14
TC 5
Z9 7
U1 0
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD AUG
PY 2012
VL 4
IS 8
BP 1279
EP 1288
DI 10.3390/v4081279
PG 10
WC Virology
SC Virology
GA 998BU
UT WOS:000308213000007
PM 23012625
ER
PT J
AU Bao, YM
Chetvernin, V
Tatusova, T
AF Bao, Yiming
Chetvernin, Vyacheslav
Tatusova, Tatiana
TI PAirwise Sequence Comparison (PASC) and Its Application in the
Classification of Filoviruses
SO VIRUSES-BASEL
LA English
DT Article
DE Filoviridae; filovirus; ICTV; International Committee on Taxonomy of
Viruses; National Center for Biotechnology Information; NCBI; PAirwise
Sequence Comparison; PASC; virus classification; virus taxonomy
ID TAXONOMY; VIRUSES; SEARCH
AB PAirwise Sequence Comparison (PASC) is a tool that uses genome sequence similarity to help with virus classification. The PASC tool at NCBI uses two methods: local alignment based on BLAST and global alignment based on Needleman-Wunsch algorithm. It works for complete genomes of viruses of several families/groups, and for the family of Filoviridae, it currently includes 52 complete genomes available in GenBank. It has been shown that BLAST-based alignment approach works better for filoviruses, and therefore is recommended for establishing taxon demarcation criteria. When more genome sequences with high divergence become available, these demarcations will most likely become more precise. The tool can compare new genome sequences of filoviruses with the ones already in the database, and propose their taxonomic classification.
C1 [Bao, Yiming; Chetvernin, Vyacheslav; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP Bao, YM (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
EM bao@ncbi.nlm.nih.gov; chetvern@ncbi.nlm.nih.gov;
tatiana@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine
FX We thank Michael Baxter and Stacy Ciufo for comments on the manuscript.
This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 12
TC 16
Z9 16
U1 1
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD AUG
PY 2012
VL 4
IS 8
BP 1318
EP 1327
DI 10.3390/v4081318
PG 10
WC Virology
SC Virology
GA 998BU
UT WOS:000308213000010
PM 23012628
ER
PT J
AU An, SS
Wang, WCH
Koziol-White, CJ
Ahn, K
Lee, DY
Kurten, RC
Panettieri, RA
Liggett, SB
AF An, Steven S.
Wang, Wayne C. H.
Koziol-White, Cynthia J.
Ahn, Kwangmi
Lee, Danielle Y.
Kurten, Richard C.
Panettieri, Reynold A., Jr.
Liggett, Stephen B.
TI TAS2R activation promotes airway smooth muscle relaxation despite
beta(2)-adrenergic receptor tachyphylaxis
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE asthma; airway smooth muscle; beta(2)-adrenergic receptor
desensitization; chloroquine; bitter taste receptor
ID BITTER TASTE RECEPTORS; BETA-ADRENERGIC-RECEPTORS; DIFFERENT MECHANISMS;
PHOSPHOLIPASE-C; MILD ASTHMA; DESENSITIZATION; AGONIST; PROTEIN;
PHOSPHORYLATION; SALMETEROL
AB An SS, Wang WC, Koziol-White CJ, Ahn K, Lee DY, Kurten RC, Panettieri RA Jr, Liggett SB. TAS2R activation promotes airway smooth muscle relaxation despite beta(2)-adrenergic receptor tachyphylaxis. Am J Physiol Lung Cell Mol Physiol 303: L304-L311, 2012. First published June 8, 2012; doi:10.1152/ajplung.00126.2012.-Recently, bitter taste receptors (TAS2Rs) were found in the lung and act to relax airway smooth muscle (ASM) via intracellular Ca2+ concentration signaling generated from restricted phospholipase C activation. As potential therapy, TAS2R agonists could be add-on treatment when patients fail to achieve adequate bronchodilation with chronic beta-agonists. The beta(2)-adrenergic receptor (beta(2)AR) of ASM undergoes extensive functional desensitization. It remains unknown whether this desensitization affects TAS2R function, by cross talk at the receptors or distal common components in the relaxation machinery. We studied intracellular signaling and cell mechanics using isolated human ASM, mouse tracheal responses, and human bronchial responses to characterize TAS2R relaxation in the context of beta(2)AR desensitization. In isolated human ASM, magnetic twisting cytometry revealed >90% loss of isoproterenol-promoted decrease in cell stiffness after 18-h exposure to albuterol. Under these same conditions of beta(2)AR desensitization, the TAS2R agonist chloroquine relaxation response was unaffected. TAS2R-mediated stimulation of intracellular Ca2+ concentration in human ASM was unaltered by albuterol pretreatment, in contrast to cAMP signaling, which was desensitized by >90%. In mouse trachea, beta(2)AR desensitization by beta-agonist amounted to 92 +/- 6.0% (P < 0.001), while, under these same conditions, TAS2R desensitization was not significant (11 +/- 3.5%). In human lung slices, chronic beta-agonist exposure culminated in 64 +/- 5.7% (P < 0.001) desensitization of beta(2)AR-mediated dilation of carbachol-constricted airways that was reversed by chloroquine. We conclude that there is no evidence for physiologically relevant cross-desensitization of TAS2R-mediated ASM relaxation from chronic beta-agonist treatment. These findings portend a favorable therapeutic profile for TAS2R agonists for the treatment of bronchospasm in asthma or chronic obstructive lung disease.
C1 [An, Steven S.; Lee, Danielle Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Program Resp Biol & Lung Dis, Baltimore, MD 21205 USA.
[Wang, Wayne C. H.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Koziol-White, Cynthia J.; Panettieri, Reynold A., Jr.] Univ Penn, Med Ctr, Div Pulm Allergy & Crit Care, Airways Biol Initiat, Philadelphia, PA 19104 USA.
[Ahn, Kwangmi] NIH, Bethesda, MD 20892 USA.
[Kurten, Richard C.] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA.
[Liggett, Stephen B.] Univ S Florida, Personalized Med Inst, Morsani Coll Med, Tampa, FL USA.
RP An, SS (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Program Resp Biol & Lung Dis, 615 N Wolfe St,Rm E-7616, Baltimore, MD 21205 USA.
EM san@jhsph.edu
FU National Heart, Lung, and Blood Institute [HL107361, HL104119, HL097796,
HL045967, HL071609]; American Asthma Foundation [Sandler: 108183];
National Institute of Environmental Health Sciences [ES013508]; Division
of Research Resources [UL1RR029884]
FX This work was supported by National Heart, Lung, and Blood Institute
Grants HL107361 (to S. S. An), HL104119 (to W. C. H. Wang), HL097796 (to
R. A. Panettieri, Jr.), and HL045967 and HL071609 (to S. B. Liggett). S.
S. An was also supported by American Asthma Foundation (Sandler: 108183)
grant, and R. A. Panettieri, Jr. by National Institute of Environmental
Health Sciences Grant ES013508,. R. C. Kurten was supported by Division
of Research Resources UL1RR029884. Human tissue used for this research
project was provided by the National Disease Research Interchange
through the generous gift of donor families.
NR 46
TC 30
Z9 32
U1 0
U2 11
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 AUG
PY 2012
VL 303
IS 4
BP L304
EP L311
DI 10.1152/ajplung.00126.2012
PG 8
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 995KJ
UT WOS:000308006600004
PM 22683571
ER
PT J
AU Hoffman, JM
Brown, ED
Chan, L
Dikmen, S
Temkin, N
Bell, KR
AF Hoffman, Jeanne M.
Brown, Elena Donoso
Chan, Leighton
Dikmen, Sureyya
Temkin, Nancy
Bell, Kathleen R.
TI Change in Inpatient Rehabilitation Admissions for Individuals With
Traumatic Brain Injury After Implementation of the Medicare Inpatient
Rehabilitation Facility Prospective Payment System
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Brain injuries; Medicare; Rehabilitation
ID LENGTH-OF-STAY; HOSPITALS; OUTCOMES; CARE; PERFORMANCE; SEVERITY;
IMPACT; TIME
AB Hoffman JM, Donoso Brown E, Chan L, Dikmen S, Temkin N, Bell KR. Change in inpatient rehabilitation admissions for individuals with traumatic brain injury after implementation of the Medicare inpatient rehabilitation facility prospective payment system. Arch Phys Med Rehabil 2012;93: 1305-12.
Objective: To evaluate the impact of Medicare's inpatient rehabilitation facility (IRF) prospective payment system (PPS) on use of inpatient rehabilitation for individuals with traumatic brain injury (TBI).
Design: Retrospective cohort study of patients with TBI.
Setting: One hundred twenty-three level I and II trauma centers across the U.S. who contributed data to the National Trauma Data Bank. Participants: Patients (N = 135,842) with TBI and an Abbreviated Injury Score of the head of 2 or greater admitted to trauma centers between 1995 and 2004.
Interventions: None.
Main Outcome Measure: Discharge location: IRF, skilled nursing facility, home, and other hospitals.
Results: Compared with inpatient rehabilitation admissions before IRF PPS came into effect, demographic characteristics of admired patients changed. Those admitted to acute care trauma centers after PPS was enacted (January 2002) were older and nonwhite. No differences were found in rates of injury between men and women. Over time, there was a significant drop in the percent of patients being discharged to inpatient rehabilitation, which varied by region, but was found across all insurance types. In a logistic regression, after controlling for patient characteristics (age, sex, race), injury characteristics (cause, severity), insurance type, and facility, the of being discharged to an IRF after a TBI decreased 16% after Medicare's IRF PPS system was enacted.
Conclusions: The enactment of the Medicare PPS appears to be associated with a reduction in the chance that patients receive inpatient rehabilitation treatment after a TBI. The impact of these changes on the cost, quality of care, and patient outcome is unknown and should be addressed in future studies.
C1 [Hoffman, Jeanne M.; Brown, Elena Donoso; Dikmen, Sureyya; Temkin, Nancy; Bell, Kathleen R.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Dikmen, Sureyya; Temkin, Nancy] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
[Dikmen, Sureyya] Univ Washington, Dept Psychiat & Behav Med, Seattle, WA 98195 USA.
[Temkin, Nancy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Hoffman, JM (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA.
EM jeanneh@u.washington.edu
OI Donoso Brown, Elena/0000-0002-0166-8198
FU Department of Education, National Institute on Disability and
Rehabilitation Research Traumatic Brain Injury Model System Funding
[H133A070032]
FX Supported by the Department of Education, National Institute on
Disability and Rehabilitation Research Traumatic Brain Injury Model
System Funding (grant no. H133A070032): and resources from the
intramural program of the National Institutes of Health.
NR 24
TC 4
Z9 4
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2012
VL 93
IS 8
BP 1305
EP 1312
DI 10.1016/j.apmr.2012.04.030
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 983XJ
UT WOS:000307151700002
PM 22840827
ER
PT J
AU Ottenbacher, KJ
Jette, AM
Fuhrer, MJ
Granger, CV
AF Ottenbacher, Kenneth J.
Jette, Alan M.
Fuhrer, Marcus J.
Granger, Carl V.
TI Looking Back and Thinking Forward: 20 Years of Disability and
Rehabilitation Research
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Comment; Rehabilitation; Review
AB The National Center for Medical Rehabilitation Research recently celebrated its 20th Anniversary. The celebration included a symposium highlighting advances in rehabilitation science over the past 2 decades. The anniversary also reminds us of the challenges that remain in order to strengthen the foundation of disability and rehabilitation research. These challenges have been described in 3 reports published by the Institute of Medicine (IOM) in 1991, 1997, and 2007. Three areas of concern appear across the IOM reports. These include (1) the lack of a comprehensive disability monitoring program, (2) the need for better integration and coordination of federally supported disability research, and (3) funding levels that are inconsistent with the current and projected impacts of disability on individuals, families, and communities. In this commentary we examine the lack of progress in addressing the recommendations contained in the IOM reports. We conclude that renewed efforts by consumers, clinicians, educators, researchers, administrators, and policy makers are needed to achieve the promise of rehabilitation and disability science identified 20 years ago.
C1 [Ottenbacher, Kenneth J.] Univ Texas Med Branch, Div Rehabil Sci, Sch Hlth Profess, Galveston, TX 77555 USA.
[Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA.
[Jette, Alan M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Fuhrer, Marcus J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Granger, Carl V.] SUNY Buffalo, Uniform Data Syst Med Rehabil, Buffalo, NY 14260 USA.
[Granger, Carl V.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA.
RP Ottenbacher, KJ (reprint author), Univ Texas Med Branch, Div Rehabil Sci, Sch Hlth Profess, 301 Univ Blvd, Galveston, TX 77555 USA.
EM kottenba@utmb.edu
OI Jette, Alan/0000-0002-2117-9973
NR 8
TC 1
Z9 1
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2012
VL 93
IS 8
BP 1392
EP 1394
DI 10.1016/j.apmr.2012.02.028
PG 3
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 983XJ
UT WOS:000307151700015
PM 22425964
ER
PT J
AU Sheehan, FT
Babushkina, A
Alter, KE
AF Sheehan, Frances T.
Babushkina, Anna
Alter, Katharine E.
TI Kinematic Determinants of Anterior Knee Pain in Cerebral Palsy: A
Case-Control Study
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Kinematics; Magnetic resonance imaging; Patellofemoral joint;
Rehabilitation; Tibiofemoral joint
ID FUNCTION CLASSIFICATION-SYSTEM; FEMORAL EXTENSION OSTEOTOMY; PATELLAR
TENDON ADVANCEMENT; PERSISTENT CROUCH GAIT; IN-VIVO; PATELLOFEMORAL
PAIN; TIBIOFEMORAL KINEMATICS; CHILDREN; ADULTS; DISTAL
AB Objective: To quantify the role patellofemoral and tibiofemoral kinematics may play in development of anterior knee pain (AKP) in individuals with cerebral palsy (CP).
Design: Case-control.
Setting: Clinical research center.
Participants: Knees from individuals with diagnosed CP (n=20) and control knees (n=40) were evaluated. Controls were matched for sex and age based on the group average. Matching by height and weight was a secondary priority. Subjects in the control cohort were asymptomatic with no history of lower leg abnormalities, surgery, or major injury. Only individuals who were physically capable of sustaining slow, cyclic knee flexion-extension for 2.5 minutes and had no contraindications to magnetic resonance imaging were enrolled. Both groups were samples of convenience.
Interventions: Not applicable.
Main Outcome Measures: Three-dimensional patellofemoral and tibiofemoral joint kinematics, acquired during active leg extension, under volitional control.
Results: Participants with CP and AKP (n=8) demonstrated significantly greater patellofemoral extension, valgus rotation, and superior and posterior displacement relative to controls and to the subgroup of participants with CP and no AKP (n=12). Patellofemoral extension discriminated AKP in individuals with CP with 100% accuracy.
Conclusions: In quantifying the 3-dimensional, in vivo knee joint kinematics during a volitional extension task, kinematic markers that discriminate AKP in individuals with CP were identified. This provides an ability to predict which individuals with CP are most likely to develop AKP and could enable aggressive conservative treatment, aimed at reducing patella alta and excessive patellofemoral extension, to be prescribed before considering surgical options. The current findings will likely lead to improved clinical diagnostics and interventions for individuals with CP, with the ultimate goal of helping maintain, if not improve, functional mobility throughout the lifespan.
C1 [Sheehan, Frances T.; Alter, Katharine E.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Babushkina, Anna] Georgetown Univ Hosp, Dept Orthopaed Surg, Washington, DC 20007 USA.
[Alter, Katharine E.] Johns Hopkins Hlth Syst Corp, Mt Washington Pediat Hosp, Baltimore, MD USA.
[Alter, Katharine E.] Univ Maryland, Med Syst Corp, Baltimore, MD 21201 USA.
RP Sheehan, FT (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bldg 10,CRC RM 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA.
EM sheehan@cc.nih.gov
RI sheehan, frances/B-6962-2009
FU Intramural Research Program of the National Institutes of Health (NIH);
Clinical Center at the NIH; Diagnostic Radiology Department at the
National Institutes of Health
FX Supported by the Intramural Research Program of the National Institutes
of Health (NIH), and the Clinical Center at the NIH.; We thank Sara
Sadeghi, Abrahm Behnam, MSE, Cris Zampieri-Gallagher, PhD, Bonnie
Damaska, and the Diagnostic Radiology Department at the National
Institutes of Health for their support and research time.
NR 54
TC 5
Z9 6
U1 4
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2012
VL 93
IS 8
BP 1431
EP 1440
DI 10.1016/j.apmr.2012.03.022
PG 10
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 983XJ
UT WOS:000307151700021
PM 22465585
ER
PT J
AU Mannelli, M
Lenders, JWM
Pacak, K
Parenti, G
Eisenhofer, G
AF Mannelli, Massimo
Lenders, Jacques W. M.
Pacak, Karel
Parenti, Gabriele
Eisenhofer, Graeme
TI Subclinical phaeochromocytoma
SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE phaeochromocytoma; paraganglioma; subclinical; catecholamines;
incidentalomas; malignant; susceptibility genes
ID ENDOCRINE NEOPLASIA TYPE-2; HIPPEL-LINDAU-SYNDROME; TUMOR-SUPPRESSOR
GENE; SUCCINATE-DEHYDROGENASE; ADRENAL MASSES; NONFUNCTIONING
PHEOCHROMOCYTOMA; UNSUSPECTED PHEOCHROMOCYTOMA; SECRETING
PHEOCHROMOCYTOMA; PLASMA METHOXYTYRAMINE; SYMPATHETIC ACTIVITY
AB Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy studies indicate that relatively large numbers of these tumours remain undiagnosed during life. This may reflect non-specific signs and symptoms and low medical alertness in evaluating the clinical picture or it may reflect a silent clinical presentation - the subclinical phaeochromocytoma. The associated clinical picture depends on the capacity of the tumours to release catecholamines and sometimes biologically active peptides. Hypertension is the hallmark of catecholamine release, but the amount, type and pattern of catecholamine secretion is extremely variable. Some tumours have low or intermittent secretory activity, some produce mainly or solely dopamine, while others very rarely do not synthesize or release any catecholamines (non-secretory or non-functional tumours). Such tumours may present with mild or even absent signs and symptoms of catecholamine excess. Low secretory activity may reflect small tumour size or differences in secretory phenotypes associated with the biochemical and genetic background of the tumours. Tumours due to succinate dehydrogenase subunit 8 mutations are often subclinical, poorly differentiated, contain low amounts of catecholamines, and are usually malignant at diagnosis. Adrenoceptor desensitization can result in a subclinical presentation, even when catecholamine levels are high. Subclinical phaeochromocytomas are often discovered as incidentalomas during radiological procedures or during routine screening for phaeochromocytoma in carriers of mutations in one of the ten currently identified tumour susceptibility genes. Undiagnosed phaeochromocytomas, whether or not subclinical and even if biologically benign, may cause extremely deleterious consequences or even death, following abrupt release of catecholamines. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, I-50139 Florence, Italy.
[Mannelli, Massimo] Ist Toscano Tumori, Florence, Italy.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands.
[Pacak, Karel] NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Parenti, Gabriele] Univ Careggi, Azienda Osped, I-50134 Florence, Italy.
[Eisenhofer, Graeme] Univ Dresden, Dept Med, D-01307 Dresden, Germany.
[Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
RP Mannelli, M (reprint author), Univ Florence, Dept Clin Pathophysiol, Viale Pieraccini 6, I-50139 Florence, Italy.
EM m.mannelli@dfc.unifi.it; j.lenders@aig.umcn.nl; karel@mail.nih.gov;
gabrieleparenti@libero.it; Graeme.Eisenhofer@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015;
OI Mannelli, Massimo/0000-0002-8001-9857
FU Intramural NIH HHS [Z01 HD008735-07]
NR 66
TC 26
Z9 28
U1 0
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-690X
J9 BEST PRACT RES CL EN
JI Best Pract. Res. Clin. Endoc. Metab.
PD AUG
PY 2012
VL 26
IS 4
BP 507
EP 515
DI 10.1016/j.beem.2011.10.008
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 994FY
UT WOS:000307917500011
PM 22863392
ER
PT J
AU Lamers, F
Burstein, M
He, JP
Avenevoli, S
Angst, J
Merikangas, KR
AF Lamers, Femke
Burstein, Marcy
He, Jian-ping
Avenevoli, Shelli
Angst, Jules
Merikangas, Kathleen R.
TI Structure of major depressive disorder in adolescents and adults in the
US general population
SO BRITISH JOURNAL OF PSYCHIATRY
LA English
DT Article
ID NATIONAL COMORBIDITY SURVEY; LATENT CLASS ANALYSIS; SUPPLEMENT NCS-A;
WORLD-HEALTH-ORGANIZATION; ATYPICAL DEPRESSION; YOUNG-ADULTS; CLINICAL
CHARACTERISTICS; MENTAL-DISORDERS; PRIMARY-CARE; SYMPTOMS
AB Background
Although techniques such as latent class analysis have been used to derive empirically based subtypes of depression in adult samples, there is limited information on subtypes of depression in youth.
Aims
To identify empirically based subtypes of depression in a nationally representative sample of US adolescents, and to test the comparability of subtypes of depression in adolescents with those derived from a nationally representative sample of adults.
Method
Respondents included 912 adolescents and 805 adults with a 12-month major depressive disorder, selected from the National Comorbidity Survey Adolescent Supplement and the National Comorbidity Survey Replication samples respectively. Latent class analysis was used to identify subtypes of depression across samples. Sociodemographic and clinical correlates of derived subtypes were also examined to establish their validity.
Results
Three subtypes of depression were identified among adolescents, whereas four subtypes were identified among adults. Two of these subtypes displayed similar diagnostic profiles across adolescent and adult samples (P = 0.43); these subtypes were labelled 'severe typical' (adults 45%, adolescents 35%) and 'atypical' (adults 16%, adolescents 26%). The latter subtype was characterised by increased appetite and weight gain.
Conclusions
The structure of depression observed in adolescents is highly similar to the structure observed in adults. Longitudinal research is necessary to evaluate the stability of these subtypes of depression across development.
C1 [Merikangas, Kathleen R.] NIMH, NIH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Lamers, Femke; Burstein, Marcy; He, Jian-ping] NIMH, Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
[Angst, Jules] Univ Zurich, Hosp Psychiat, Zurich, Switzerland.
RP Merikangas, KR (reprint author), NIMH, NIH, Genet Epidemiol Res Branch, Intramural Res Program, 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 [Z01 MH002808-08, U01-MH60220];
Netherlands Organisation for Scientific Research (NWO)
FX The study was supported by the Intramural Research Program of the
National Institute of Mental Health (Z01 MH002808-08). The National
Comorbidity Survey (NCS) Adolescent Supplement and the larger programme
of related NCS surveys are supported by the National Institute of Mental
Health (U01-MH60220). The views and opinions expressed in this article
are those of the authors and should not be construed to represent the
views of any of the sponsoring organisations, agencies or the US
government. F.L. is supported by a Rubicon Fellowship from The
Netherlands Organisation for Scientific Research (NWO).
NR 56
TC 26
Z9 26
U1 1
U2 17
PU ROYAL COLLEGE OF PSYCHIATRISTS
PI LONDON
PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG,
ENGLAND
SN 0007-1250
J9 BRIT J PSYCHIAT
JI Br. J. Psychiatry
PD AUG
PY 2012
VL 201
IS 2
BP 143
EP 150
DI 10.1192/bjp.bp.111.098079
PG 8
WC Psychiatry
SC Psychiatry
GA 987NI
UT WOS:000307423800014
PM 22700082
ER
PT J
AU Chong, CE
Lim, KP
Gan, CP
Marsh, CA
Zain, RB
Abraham, MT
Prime, SS
Teo, SH
Gutkind, JS
Patel, V
Cheong, SC
AF Chong, Chan Eng
Lim, Kue Peng
Gan, Chai Phei
Marsh, Christina A.
Zain, Rosnah Binti
Abraham, Mannil Thomas
Prime, Stephen S.
Teo, Soo-Hwang
Gutkind, J. Silvio
Patel, Vyomesh
Cheong, Sok Ching
TI Over-expression of MAGED4B increases cell migration and growth in oral
squamous cell carcinoma and is associated with poor disease outcome
SO CANCER LETTERS
LA English
DT Article
DE MAGED4B; Melanoma antigens; Oral Squamous Cell Carcinoma (OSCC);
Migration
ID MELANOMA-ASSOCIATED ANTIGENS; GENE FAMILY; NECK-CANCER; LUNG-CANCER; RHO
GTPASES; T-CELLS; APOPTOSIS; INVASION; IDENTIFICATION; HEAD
AB MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo. and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Chong, Chan Eng; Lim, Kue Peng; Gan, Chai Phei; Teo, Soo-Hwang; Cheong, Sok Ching] Sime Darby Med Ctr, Outpatient Ctr, Canc Res Initiat Fdn CARIF, Oral Canc Res Team, Subang Jaya 47500, Selangor, Malaysia.
[Marsh, Christina A.; Gutkind, J. Silvio; Patel, Vyomesh] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Zain, Rosnah Binti] Univ Malaya, Oral Canc Res & Coordinating Ctr, Kuala Lumpur 50603, Malaysia.
[Zain, Rosnah Binti] Univ Malaya, Fac Dent, Dept Oral Pathol Oral Med & Periodontol, Kuala Lumpur 50603, Malaysia.
[Abraham, Mannil Thomas] Hosp Tengku Ampuan Rahimah, Dept Oral & Maxillofacial Surg, Klang, Malaysia.
[Prime, Stephen S.] Bristol Dent Hosp & Sch, Div Oral Med Pathol & Microbiol, Dept Oral & Dent Sci, Bristol BS1 2LY, Avon, England.
[Cheong, Sok Ching] Univ Malaya, Fac Dent, Dept Oral & Maxillofacial Surg, Kuala Lumpur 50603, Malaysia.
RP Cheong, SC (reprint author), Sime Darby Med Ctr, Outpatient Ctr, Canc Res Initiat Fdn CARIF, Oral Canc Res Team, 2nd Floor, Subang Jaya 47500, Selangor, Malaysia.
EM sokching.cheong@carif.com.my
RI Zain, Rosnah/B-8054-2010; Management Center, Dental
Research/C-2478-2013; Teo, Soo-hwang/H-2353-2014
FU Ministry of Science, Technology and Innovation (MOST)) of Malaysia [RMK8
06-00-00-0000]; University of Malaya [UM.C/625/1/HIR/010]; Cancer
Research Initiatives Foundation; UICC/ICRETT Fellowships
FX This study was funded by the Ministry of Science, Technology and
Innovation (MOST)) of Malaysia (RMK8 06-00-00-0000), University of
Malaya (UM.C/625/1/HIR/010) and other sponsors of the Cancer Research
Initiatives Foundation. Collaborative work between our laboratory and
Professor Stephen Prime and Dr. J.S. Gutkind were supported by
UICC/ICRETT Fellowships to S.C. Cheong and C.P. Gan. We thank Professor
Y. Nakamura and Dr. H. Zembutsu for help with bioinformatics analysis of
MAGED4B expression in various tissue types. We thank our collaborating
partners in the Oral Cancer Research and Co-ordinating Centre,
University Malaya (OCRCC) and also, the Ministry Of Health, Malaysia.
CARIF is a non-profit research organization. We are committed to an
understanding of cancer prevention, diagnosis and treatment through a
fundamental research programme.
NR 50
TC 11
Z9 11
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD AUG 1
PY 2012
VL 321
IS 1
BP 18
EP 26
DI 10.1016/j.canlet.2012.03.025
PG 9
WC Oncology
SC Oncology
GA 991ER
UT WOS:000307684800003
PM 22459352
ER
PT J
AU Jenkins, LMM
Durell, SR
Mazur, SJ
Appella, E
AF Jenkins, Lisa M. Miller
Durell, Stewart R.
Mazur, Sharlyn J.
Appella, Ettore
TI p53 N-terminal phosphorylation: a defining layer of complex regulation
SO CARCINOGENESIS
LA English
DT Review
ID CREB-BINDING-PROTEIN; SUPPRESSOR TRANSACTIVATION DOMAIN; TUMOR
SUPPRESSION; ACTIVATION DOMAINS; TRANSCRIPTIONAL ACTIVATION;
P53-DEPENDENT APOPTOSIS; FUNCTIONAL INTERACTIONS; TERNARY COMPLEX; P300
DOMAINS; DNA-DAMAGE
AB The p53 tumor suppressor is a critical component of the cellular response to stress. As it can inhibit cell growth, p53 is mutated or functionally inactivated in most tumors. A multitude of protein-protein interactions with transcriptional cofactors are central to p53-dependent responses. In its activated state, p53 is extensively modified in both the N- and C-terminal regions of the protein. These modifications, especially phosphorylation of serine and threonine residues in the N-terminal transactivation domain, affect p53 stability and activity by modulating the affinity of protein-protein interactions. Here, we review recent findings from in vitro and in vivo studies on the role of p53 N-terminal phosphorylation. These modifications can either positively or negatively affect p53 and add a second layer of complex regulation to the divergent interactions of the p53 transactivation domain.
C1 [Jenkins, Lisa M. Miller; Durell, Stewart R.; Mazur, Sharlyn J.; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2140, Bethesda, MD 20892 USA.
EM appellae@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, USA
FX All authors are supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, USA.
NR 88
TC 35
Z9 38
U1 3
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2012
VL 33
IS 8
BP 1441
EP 1449
DI 10.1093/carcin/bgs145
PG 9
WC Oncology
SC Oncology
GA 992MO
UT WOS:000307781000002
PM 22505655
ER
PT J
AU Vermeulen, R
Zhang, LP
Spierenburg, A
Tang, XJ
Bonventre, JV
Reiss, B
Shen, M
Smith, MT
Qiu, CY
Ge, YC
Ji, ZY
Xiong, J
He, J
Hao, ZY
Liu, SW
Xie, YX
Yue, F
Guo, WH
Purdue, M
Freeman, LEB
Sabbisetti, V
Li, LY
Huang, HL
Rothman, N
Lan, Q
AF Vermeulen, Roel
Zhang, Luoping
Spierenburg, Annejet
Tang, Xiaojian
Bonventre, Joseph V.
Reiss, Boris
Shen, Min
Smith, Martyn T.
Qiu, Chuangyi
Ge, Yichen
Ji, Zhiying
Xiong, Jun
He, Jian
Hao, Zhenyue
Liu, Songwang
Xie, Yuxuan
Yue, Fei
Guo, Weihong
Purdue, Mark
Freeman, Laura E. Beane
Sabbisetti, Venkata
Li, Laiyu
Huang, Hanlin
Rothman, Nathaniel
Lan, Qing
TI Elevated urinary levels of kidney injury molecule-1 among Chinese
factory workers exposed to trichloroethylene
SO CARCINOGENESIS
LA English
DT Article
ID BETA-D-GLUCOSAMINIDASE; BETA-2-MICROGLOBULIN; BIOMARKERS; EXCRETION;
PROTEIN; KIM-1
AB Epidemiological studies suggest that trichloroethylene (TCE) exposure may be associated with renal cancer. The biological mechanisms involved are not exactly known although nephrotoxicity is believed to play a role. Studies on TCE nephrotoxicity among humans, however, have been largely inconsistent. We studied kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable unexposed controls were included in the present analyses. Personal TCE exposure measurements were taken over a 2-week period before urine collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration permissible exposure limit (100 ppm 8 h TWA), with a mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione S transferase (GST) alpha were elevated among the exposed subjects as compared with the unexposed controls with a strong exposure-response association between individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first report to use a set of sensitive nephrotoxicity markers to study the possible effects of TCE on the kidneys. The findings suggest that at relatively low occupational exposure levels a toxic effect on the kidneys can be observed. This finding supports the biological plausibility of linking TCE exposure and renal cancer.
C1 [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, NL-3584 CK Utrecht, Netherlands.
[Zhang, Luoping; Smith, Martyn T.; Ji, Zhiying; Guo, Weihong] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Tang, Xiaojian; Qiu, Chuangyi; Ge, Yichen; Xie, Yuxuan; Yue, Fei; Li, Laiyu; Huang, Hanlin] Guangdong Poison Control Ctr, Guangzhou, Guangdong, Peoples R China.
[Bonventre, Joseph V.; Sabbisetti, Venkata] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal,Dept Med, Boston, MA 02115 USA.
[Shen, Min; Purdue, Mark; Freeman, Laura E. Beane; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China.
[He, Jian] Zhongshan Ctr Dis Control & Prevent, Zhongshan, Guangdong, Peoples R China.
[Hao, Zhenyue] Inst Breast Canc Res, Toronto, ON, Canada.
[Hao, Zhenyue] Univ Hlth Network, Toronto, ON, Canada.
[Liu, Songwang] Qiaotou Hosp, Dongguan, Guangdong, Peoples R China.
RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands.
EM R.C.H.Vermeulen@uu.nl
RI Vermeulen, Roel/F-8037-2011; Beane Freeman, Laura/C-4468-2015
OI Vermeulen, Roel/0000-0003-4082-8163; Beane Freeman,
Laura/0000-0003-1294-4124
FU National Institutes of Health, National Cancer Institute; National
Institute of Environmental Health Sciences [P42ES04705, P30ES01896];
Northern California Center for Occupational and Environmental Health;
Department of Science and Technology of Guangdong Province, China
[2007A050100004]; Department of Science and Technology of Guangdong
Province, P.R. China [2007A050100004]; US NIH [DK072381]
FX This work was supported by intramural funds from the National Institutes
of Health, National Cancer Institute, and grants from the National
Institute of Environmental Health Sciences (P42ES04705 and P30ES01896),
the Northern California Center for Occupational and Environmental
Health, and the Department of Science and Technology of Guangdong
Province, China (2007A050100004), and a grant from the Department of
Science and Technology of Guangdong Province, P.R. China (2007A050100004
to XT). JVB was supported by US NIH grant DK072381.
NR 22
TC 18
Z9 19
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2012
VL 33
IS 8
BP 1538
EP 1541
DI 10.1093/carcin/bgs191
PG 4
WC Oncology
SC Oncology
GA 992MO
UT WOS:000307781000013
PM 22665366
ER
PT J
AU Sill, MW
Rubinstein, L
Litwin, S
Yothers, G
AF Sill, Michael W.
Rubinstein, Larry
Litwin, Samuel
Yothers, Greg
TI A method for utilizing co-primary efficacy outcome measures to screen
regimens for activity in two-stage Phase II clinical trials
SO CLINICAL TRIALS
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; MULTIPLE OUTCOMES; END-POINTS; DESIGNS;
CANCER; BEVACIZUMAB; PERSISTENT; RECURRENT
AB Background Most Phase II clinical trials utilize a single primary end point to determine the promise of a regimen for future study. However, many disorders manifest themselves in complex ways. For example, migraine headaches can cause pain, auras, photophobia, and emesis. Investigators may believe that a drug is effective at reducing migraine pain and the severity of emesis during an attack. Nevertheless, they could still be interested in proceeding with the development of the drug if it is effective against only one of these symptoms. Such a study would be a candidate for a clinical trial with co-primary end points.
Purpose The purpose of the article is to provide a method for designing a single arm, two-stage clinical trial with dichotomous co-primary end points of efficacy that has the ability to detect activity on either response measure with high probability when the drug is active on one or both measures, while at the same time rejecting the drug with high probability when there is little activity on both dimensions. The design enables early closure for futility and is flexible with regard to attained accrual.
Methods The design is proposed in the context of cancer clinical trials with tumor response and progression-free survival (PFS) status after a certain period. Both end points are assumed to be distributed as binomial random variables, and uninteresting probabilities of success are determined from historical controls. Given the necessity of accrual flexibility, exhaustive searching algorithms to find optimum designs do not seem feasible at this time. Instead, critical values are determined for realized sample sizes using specific procedures. Then accrual windows are found to achieve a design's desired level of significance, probability of early termination (PET), and power.
Results The design is illustrated with a clinical trial that examined bevacizumab in patients with recurrent endometrial cancer. This study was negative by tumor response but positive by 6-month PFS. The procedure was compared to modified procedures in the literature, indicating that the method is competitive.
Limitations Although the procedure allows investigators to construct designs with desired levels of significance and power, the PET under the null hypothesis is smaller than for single end point studies.
Conclusions The impact of adding an additional end point on the sample size is often minimal, but the study gains sensitivity to activity on another dimension of treatment response. The operating characteristics are fairly robust to the level of association between the two end points. Software is available online. Clinical Trials 2012; 9: 385--395. http://ctj.sagepub.com
C1 [Sill, Michael W.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
[Sill, Michael W.] SUNY Buffalo, Buffalo, NY 14260 USA.
[Rubinstein, Larry] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Litwin, Samuel] Fox Chase Canc Ctr, Biostat Facil, Philadelphia, PA 19111 USA.
[Yothers, Greg] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Yothers, Greg] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA.
RP Sill, MW (reprint author), Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Elm & Carlton St, Buffalo, NY 14263 USA.
EM msill@gogstats.org
OI Yothers, Greg/0000-0002-7965-7333
FU National Cancer Institute [CA37517]; NIH [P30 CA 06927]; NCI FCCC-UPenn
ovarian cancer SPORE [P50 CA083638]
FX The research by Michael W Sill was supported in part by the National
Cancer Institute grant to the Gynecologic Oncology Group Statistical and
Data Center (CA37517). The research by Samuel Litwin was supported in
part by NIH grant P30 CA 06927, NCI FCCC-UPenn ovarian cancer SPORE P50
CA083638, and an appropriation from the Commonwealth of Pennsylvania.
NR 22
TC 11
Z9 11
U1 1
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD AUG
PY 2012
VL 9
IS 4
BP 385
EP 395
DI 10.1177/1740774512450101
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 995BV
UT WOS:000307982600002
PM 22811448
ER
PT J
AU Kontzias, A
Kotlyar, A
Laurence, A
Changelian, P
O'Shea, JJ
AF Kontzias, Apostolos
Kotlyar, Alexander
Laurence, Arian
Changelian, Paul
O'Shea, John J.
TI Jakinibs: a new class of kinase inhibitors in cancer and autoimmune
disease
SO CURRENT OPINION IN PHARMACOLOGY
LA English
DT Article
ID ACTIVE RHEUMATOID-ARTHRITIS; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC
MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC
MYELOID-LEUKEMIA; PROTEIN-TYROSINE KINASE; JAK INHIBITOR; TOFACITINIB
CP-690,550; INADEQUATE RESPONSE; MYELOPROLIFERATIVE NEOPLASMS
AB Cytokines are critical for normal cell growth and immunoregulation but also contribute to growth of malignant cells and drive immune-mediated disease. A large subset of immunoregulatory cytokines uses the type I and type II cytokine receptors and pharmacological targeting of these cytokines/cytokines receptors has proven to be efficacious in treating immune and inflammatory diseases. These receptors rely on Janus family of kinases (Jaks) for signal transduction. Recently the first Jak inhibitor (jakinib) has been approved by the FDA and a second has been recommended for approval. Many other Jakinibs are likely to follow and in this brief review, we will discuss the state-of-the art of this new class of pharmacological agents.
C1 [Kotlyar, Alexander; Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Kontzias, Apostolos] NIAMSD, Pediat Rheumatol Branch, NIH, Bethesda, MD 20892 USA.
[Changelian, Paul] Infin Pharmaceut, Cambridge, MA USA.
RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM osheajo@mail.nih.gov
RI Laurence, Arian/A-8770-2009
OI Laurence, Arian/0000-0003-0942-8292
FU Intramural NIH HHS [ZIA AR041106-17]
NR 65
TC 54
Z9 54
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4892
J9 CURR OPIN PHARMACOL
JI Curr. Opin. Pharmacol.
PD AUG
PY 2012
VL 12
IS 4
BP 464
EP 470
DI 10.1016/j.coph.2012.06.008
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 999BS
UT WOS:000308284700014
PM 22819198
ER
PT J
AU Yaro, AS
Traore, AI
Huestis, DL
Adamou, A
Timbine, S
Kassogue, Y
Diallo, M
Dao, A
Traore, SF
Lehmann, T
AF Yaro, Alpha S.
Traore, Adama I.
Huestis, Diana L.
Adamou, Abdoulaye
Timbine, Seydou
Kassogue, Yaya
Diallo, Moussa
Dao, Adama
Traore, Sekou F.
Lehmann, Tovi
TI Dry season reproductive depression of Anopheles gambiae in the Sahel
SO JOURNAL OF INSECT PHYSIOLOGY
LA English
DT Article
DE Aestivation; Diapause; Dormancy; Malaria; Seasonality; Reproduction
ID EFFECTIVE POPULATION-SIZE; MALARIA VECTOR CONTROL; WEST-AFRICA;
MOLECULAR-FORMS; DIPTERA-CULICIDAE; CULEX-PIPIENS; DESICCATION
RESISTANCE; INCIPIENT SPECIATION; LARVAL DEVELOPMENT; CHROMOSOMAL FORMS
AB The African malaria mosquito, Anopheles gambiae, is widespread south of the Sahara including in dry savannahs and semi-arid environments where no surface water exists for several months a year. Adults of the M form of An. gambiae persist through the long dry season, when no surface waters are available, by increasing their maximal survival from 4 weeks to 7 months. Dry season diapause (aestivation) presumably underlies this extended survival. Diapause in adult insects is intrinsically linked to depressed reproduction. To determine if reproduction of the Sahelian M form is depressed during the dry season, we assessed seasonal changes in oviposition, egg batch size, and egg development, as well as insemination rate and blood feeding in wild caught mosquitoes. Results from xeric Sahelian and riparian populations were compared. Oviposition response in the Sahelian M form dropped from 70% during the wet season to 20% during the dry season while the mean egg batch size among those that laid eggs fell from 173 to 101. Correspondingly, the fraction of females that exhibited gonotrophic dissociation increased over the dry season from 5% to 45%, while a similar fraction of the population retained developed eggs despite having access to water. This depression in reproduction the Sahelian M form was not caused by a reduced insemination rate. Seasonal variation in these reproductive parameters of the riparian M form population was less extreme and the duration of reproductive depression was shorter. Blood feeding responses did not change with the season in either population. Depressed reproduction during the dry season in the Sahelian M form of An. gambiae provides additional evidence for aestivation and illuminates the physiological processes involved. The differences between the Sahelian and riparian population suggest an adaptive cline in aestivation phenotypes between populations only 130 km apart. Published by Elsevier Ltd.
C1 [Huestis, Diana L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Yaro, Alpha S.; Traore, Adama I.; Adamou, Abdoulaye; Timbine, Seydou; Kassogue, Yaya; Diallo, Moussa; Dao, Adama; Traore, Sekou F.] MRTC, Fac Med Pharm & Odonto Stomatol, Bamako, Mali.
RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2W-09-C, Rockville, MD 20852 USA.
EM yaro@mrtcbko.org; TraoreA@MRTCBKO.org; huestisdl@niaid.nih.gov;
Adamou@MRTCBKO.org; timbines@mrtcbko.org; ykassogue@MRTCBKO.org;
moussad@mrtcbko.org; adama@MRTCBKO.org; cheick@mrtcbko.org;
tlehmann@niaid.nih.gov
OI Huestis, Diana/0000-0001-6649-4785
FU NIAID, NIH
FX We are grateful to the residents of M'Piabougou, N'Gabakoro Droit, and
Thierola who accommodated our studies and went out of the way in their
hospitality. We thank Drs. Martin Donnelly, Dia Elnaiem, Peter
Billingsley, and Robert Gwadz for valuable suggestions on earlier
versions of this manuscript. This study was supported by the Intramural
Research Program in NIAID, NIH.
NR 84
TC 19
Z9 19
U1 3
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-1910
J9 J INSECT PHYSIOL
JI J. Insect Physiol.
PD AUG
PY 2012
VL 58
IS 8
BP 1050
EP 1059
DI 10.1016/j.jinsphys.2012.04.002
PG 10
WC Entomology; Physiology; Zoology
SC Entomology; Physiology; Zoology
GA 983YM
UT WOS:000307154600003
PM 22609421
ER
PT J
AU Yabroff, KR
Warren, JL
AF Yabroff, K. Robin
Warren, Joan L.
TI High-Cost Imaging in Elderly Patients with Stage IV Cancer: Challenges
for Research, Policy, and Practice
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID MEDICAL EXPENDITURES; LAST YEAR; LIFE; PERFORMANCE; CARE
C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA.
EM yabroffr@mail.nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
NR 22
TC 4
Z9 4
U1 0
U2 2
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 AUG
PY 2012
VL 104
IS 15
BP 1113
EP 1114
DI 10.1093/jnci/djs316
PG 2
WC Oncology
SC Oncology
GA 992VW
UT WOS:000307809300001
PM 22851272
ER
PT J
AU Zhang, W
Shu, XO
Li, HL
Yang, G
Cai, H
Ji, BT
Gao, J
Gao, YT
Zheng, W
Xiang, YB
AF Zhang, Wei
Shu, Xiao-Ou
Li, Honglan
Yang, Gong
Cai, Hui
Ji, Bu-Tian
Gao, Jing
Gao, Yu-Tang
Zheng, Wei
Xiang, Yong-Bing
TI Vitamin Intake and Liver Cancer Risk: A Report From Two Cohort Studies
in China
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SHANGHAI WOMENS HEALTH; HEPATOCELLULAR-CARCINOMA; DIETARY ANTIOXIDANTS;
GAMMA-TOCOPHEROL; MENS HEALTH; HEPATOCARCINOGENESIS; REPRODUCIBILITY;
PREVENTION; VALIDITY; IMMUNITY
AB Background Epidemiologic studies on the relationship between vitamin intake and liver cancer risk are sparse and inconsistent.
Methods We evaluated vitamin intake from diet and supplements and risk of liver cancer in 132 837 women and men from China who were recruited into the Shanghai Women's Health Study from 1997 to 2000 or the Shanghai Men's Health Study from 2002 to 2006. In-person interviews, using a validated food-frequency questionnaire, were conducted to collect data on dietary habits. Follow-up consisted of in-person surveys and record linkage. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models with adjustment for potential confounders to compare liver cancer risk among participants with high vs low vitamin intake. All statistical tests were two-sided.
Results After excluding the first 2 years of follow-up, 267 participants (including 118 women and 149 men) developed liver cancer during an average of 10.9 (Shanghai Women's Health Study) or 5.5 (Shanghai Men's Health Study) years of follow-up. Dietary vitamin E intake was inversely associated with liver cancer risk (P-trend = .01), as was vitamin E supplement use (hazard ratio = 0.52, 95% confidence interval = 0.30 to 0.90). This association was consistent among participants with and without self-reported liver disease or a family history of liver cancer. Vitamin C and multivitamin use was associated with increased risk among participants with self-reported liver disease or family history of liver cancer, whereas intake of vitamin C and other vitamins from dietary sources was unrelated to liver cancer risk.
Conclusions Vitamin E intake, either from diet or supplements, may reduce the risk of liver cancer.
C1 [Shu, Xiao-Ou; Yang, Gong; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37203 USA.
[Zhang, Wei; Li, Honglan; Gao, Jing; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogene & Relat, Shanghai 200032, Peoples R China.
[Zhang, Wei; Li, Honglan; Gao, Jing; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,Dept Epidemiol, Shanghai 200032, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, 2525 W End Ave,Ste 600 IMPH, Nashville, TN 37203 USA.
EM xiao-ou.shu@vanderbilt.edu; ybxiang@shsci.org
FU US National Institutes of Health [R37 CA070867, R01 CA082729]; State Key
Project Specialized for Infectious Diseases of China [2008ZX10002-015,
2012ZX10002008-002]; Fogarty International Center [D43 TW008313]
FX This study was supported by grants from the US National Institutes of
Health (grant numbers R37 CA070867 to W. Zheng and R01 CA082729 to X-OS)
and the funding of the State Key Project Specialized for Infectious
Diseases of China (2008ZX10002-015 and 2012ZX10002008-002 to Y-BX). W.
Zhang was supported by a training grant from the Fogarty International
Center (D43 TW008313 to X-OS).
NR 28
TC 21
Z9 25
U1 0
U2 12
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 AUG
PY 2012
VL 104
IS 15
BP 1173
EP 1181
DI 10.1093/jnci/djs277
PG 9
WC Oncology
SC Oncology
GA 992VW
UT WOS:000307809300010
PM 22811438
ER
PT J
AU Gierach, GL
Ichikawa, L
Kerlikowske, K
Brinton, LA
Farhat, GN
Vacek, PM
Weaver, DL
Schairer, C
Taplin, SH
Sherman, ME
AF Gierach, Gretchen L.
Ichikawa, Laura
Kerlikowske, Karla
Brinton, Louise A.
Farhat, Ghada N.
Vacek, Pamela M.
Weaver, Donald L.
Schairer, Catherine
Taplin, Stephen H.
Sherman, Mark E.
TI Relationship Between Mammographic Density and Breast Cancer Death in the
Breast Cancer Surveillance Consortium
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PARENCHYMAL PATTERNS; TUMOR CHARACTERISTICS; POSTMENOPAUSAL WOMEN;
SUBSEQUENT RISK; ASSOCIATION; FEATURES; MENOPAUSE; ACCURACY; SURVIVAL;
MARKERS
AB Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors.
We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 19962005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided.
A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0cm (HR = 1.55, 95% CI = 1.14 to 2.09).
High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed.
C1 [Gierach, Gretchen L.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD USA.
[Schairer, Catherine] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Taplin, Stephen H.] NCI, Proc Care Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA.
[Ichikawa, Laura] Grp Hlth Res Inst, Seattle, WA USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Farhat, Ghada N.] Univ Balamand, Beirut, Lebanon.
[Vacek, Pamela M.] Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT USA.
[Weaver, Donald L.] Vermont Canc Ctr, Burlington, VT USA.
[Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
RP Gierach, GL (reprint author), 6120 Execut Blvd,Ste 550,Rm 5016, Rockville, MD 20852 USA.
EM gierachg@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522
FU National Institutes of Health, National Cancer Institute (NCI); NCI
[U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976,
U01CA63731, U01CA70040, HHSN261201100031C]
FX This work was supported (in part) by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute (NCI), and
the NCI-funded Breast Cancer Surveillance Consortium (U01CA63740 to KK,
U01CA86076 to DM, U01CA86082 to TO, U01CA63736 to GC, U01CA70013 to BG,
U01CA69976 to RR, U01CA63731 to DB, U01CA70040 to BY, and
HHSN261201100031C to DM).
NR 32
TC 54
Z9 54
U1 1
U2 6
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 AUG
PY 2012
VL 104
IS 16
BP 1218
EP 1227
DI 10.1093/jnci/djs327
PG 10
WC Oncology
SC Oncology
GA 998JO
UT WOS:000308234100006
PM 22911616
ER
PT J
AU Watt, TC
Inskip, PD
Stratton, K
Smith, SA
Kry, SF
Sigurdson, AJ
Stovall, M
Leisenring, W
Robison, LL
Mertens, AC
AF Watt, Tanya C.
Inskip, Peter D.
Stratton, Kayla
Smith, Susan A.
Kry, Stephen F.
Sigurdson, Alice J.
Stovall, Marilyn
Leisenring, Wendy
Robison, Leslie L.
Mertens, Ann C.
TI Radiation-Related Risk of Basal Cell Carcinoma: A Report From the
Childhood Cancer Survivor Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID NONMELANOMA SKIN-CANCER; ATOMIC-BOMB SURVIVORS; LEUKEMIA RISK; TRENDS;
TUMOR; MODEL; HEAD; NECK; CARE
AB Basal cell carcinoma (BCC) is the most common malignancy in the United States. Ionizing radiation is an established risk factor in certain populations, including cancer survivors. We quantified the association between ionizing radiation dose and the risk of BCC in childhood cancer survivors.
Participants in the Childhood Cancer Survivor Study who reported a BCC (case subjects, n = 199) were matched on age and length of follow-up to three study participants who had not developed a BCC (control subjects, n = 597). The radiation-absorbed dose (in Gy) to the BCC location was calculated based on individual radiotherapy records using a custom-designed dosimetry program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and treatment factors, therapeutic radiation dose, and surrogate markers of sun sensitivity (skin and hair color) and the risk of BCC. A linear doseresponse model was fitted to evaluate the excess odds ratio per Gy of radiation dose.
Among case subjects, 83% developed BCC between the ages of 20 and 39 years. Radiation therapy, either alone or in combination with chemotherapy, was associated with an increased risk of BCC compared with no chemotherapy or radiation. The odds ratio for subjects who received 35 Gy or more to the skin site vs no radiation therapy was 39.8 (95% CI = 8.6 to 185). Results were consistent with a linear doseresponse relationship, with an excess odds ratio per Gy of 1.09 (95% CI = 0.49 to 2.64). No other treatment variables were statistically significantly associated with an increased risk of BCC.
Radiation doses to the skin of more than 1 Gy are associated with an increased risk of BCC.
C1 [Mertens, Ann C.] Emory Univ, Dept Pediat, Aflac Canc Ctr & Blood Disorders Serv, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
[Watt, Tanya C.] UT SW Med, Dept Pediat Oncol, Dallas, TX USA.
[Inskip, Peter D.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Stratton, Kayla; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Dept Canc Prevent, Seattle, WA 98104 USA.
[Stratton, Kayla; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Dept Clin Stat, Seattle, WA 98104 USA.
[Smith, Susan A.; Kry, Stephen F.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
RP Mertens, AC (reprint author), Emory Univ, Dept Pediat, Aflac Canc Ctr & Blood Disorders Serv, Childrens Healthcare Atlanta, 2015 Uppergate Dr, Atlanta, GA 30322 USA.
EM amerten@emory.edu
OI Kry, Stephen/0000-0001-6899-197X
FU Lance Armstrong Foundation; National Cancer Institute [CA 55727,
5U2415]; National Cancer Institute/National Institutes of Health [N02
CP-2010-00-15]; Division of Cancer Epidemiology and Genetics, National
Cancer Institute, National Institutes of Health
FX This work was supported by Lance Armstrong Foundation (to ACM), the
National Cancer Institute grant (CA 55727 to LLR) and the National
Cancer Institute subgrant (5U2415 to MS), the National Cancer
Institute/National Institutes of Health contract (N02 CP-2010-00-15 to
MS), and the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health.
NR 31
TC 20
Z9 21
U1 2
U2 13
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 AUG
PY 2012
VL 104
IS 16
BP 1240
EP 1250
DI 10.1093/jnci/djs298
PG 11
WC Oncology
SC Oncology
GA 998JO
UT WOS:000308234100008
PM 22835387
ER
PT J
AU Singh, DK
Ghosh, AK
Croteau, DL
Bohr, VA
AF Singh, Dharmendra Kumar
Ghosh, Avik K.
Croteau, Deborah L.
Bohr, Vilhelm A.
TI RecQ helicases in DNA double strand break repair and telomere
maintenance
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Review
DE RecQ helicases; DNA double strand break repair; Werner syndrome; Bloom
syndrome; Rothmund Thomson syndrome; Telomere maintenance
ID ROTHMUND-THOMSON-SYNDROME; WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME
HELICASE; TOPOISOMERASE-III-ALPHA; SYNDROME GENE-PRODUCT;
SISTER-CHROMATID EXCHANGES; DAMAGED REPLICATION FORKS; S-PHASE
CHECKPOINT; HOMOLOGOUS RECOMBINATION; MAMMALIAN TELOMERES
AB Organisms are constantly exposed to various environmental insults which could adversely affect the stability of their genome. To protect their genomes against the harmful effect of these environmental insults, organisms have evolved highly diverse and efficient repair mechanisms. Defective DNA repair processes can lead to various kinds of chromosomal and developmental abnormalities. RecQ helicases are a family of evolutionarily conserved, DNA unwinding proteins which are actively engaged in various DNA metabolic processes, telomere maintenance and genome stability. Bacteria and lower eukaryotes, like yeast, have only one RecQ homolog, whereas higher eukaryotes including humans possess multiple RecQ helicases. These multiple RecQ helicases have redundant and/or non-redundant functions depending on the types of DNA damage and DNA repair pathways. Humans have five different RecQ helicases and defects in three of them cause autosomal recessive diseases leading to various kinds of cancer predisposition and/or aging phenotypes. Emerging evidence also suggests that the RecQ helicases have important roles in telomere maintenance. This review mainly focuses on recent knowledge about the roles of RecQ helicases in DNA double strand break repair and telomere maintenance which are important in preserving genome integrity. Published by Elsevier B.V.
C1 [Singh, Dharmendra Kumar; Ghosh, Avik K.; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU National Institute on Aging, NIH
FX We would like to thank Drs. Venkateswarlu Popuri and Haritha
Vallabhaneni for critical reading of the manuscript. This work was in
part supported by funds from the Intramural Program of the National
Institute on Aging, NIH.
NR 129
TC 29
Z9 29
U1 0
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD AUG 1
PY 2012
VL 736
IS 1-2
SI SI
BP 15
EP 24
DI 10.1016/j.mrfmmm.2011.06.002
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 999BK
UT WOS:000308283900004
PM 21689668
ER
PT J
AU Trzeciak, AR
Mohanty, JG
Jacob, KD
Barnes, J
Ejiogu, N
Lohani, A
Zonderman, AB
Rifkind, JM
Evans, MK
AF Trzeciak, Andrzej R.
Mohanty, Joy G.
Jacob, Kimberly D.
Barnes, Janice
Ejiogu, Ngozi
Lohani, Althaf
Zonderman, Alan B.
Rifkind, Joseph M.
Evans, Michele K.
TI Oxidative damage to DNA and single strand break repair capacity:
Relationship to other measures of oxidative stress in a population
cohort
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE Oxidative stress; Aging; DNA oxidative lesions; DNA repair; Comet assay;
Red blood cell glutathione (RBC GSH); Fluorescent heme degradation
products; High-sensitivity C-reactive protein (hs-CRP)
ID RED-BLOOD-CELLS; COMET ASSAY; HUMAN-LYMPHOCYTES; HYDROGEN-PEROXIDE; HEME
DEGRADATION; IONIZING-RADIATION; METABOLIC SYNDROME; BASE DAMAGE; AGE;
RACE
AB It is well accepted that oxidative DNA repair capacity, oxidative damage to DNA and oxidative stress play central roles in aging and disease development. However, the correlation between oxidative damage to DNA, markers of oxidant stress and DNA repair capacity is unclear. In addition, there is no universally accepted panel of markers to assess oxidative stress in humans. Our interest is oxidative damage to DNA and its correlation with DNA repair capacity and other markers of oxidative stress. We present preliminary data from a small comet study that attempts to correlate single strand break (SSB) level with single strand break repair capacity (SSB-RC) and markers of oxidant stress and inflammation. In this limited study of four very small age-matched 24-individual groups of male and female whites and African-Americans aged 30-64 years, we found that females have higher single strand break (SSB) levels than males (p = 0.013). There was a significant negative correlation between SSB-RC and SSB level (p = 0.041). There was a positive correlation between SSBs in African American males with both heme degradation products (p=0.008) and high-sensitivity C-reactive protein (hs-CRP) (p = 0.022). We found a significant interaction between hs-CRP and sex in their effect on residual DNA damage (p =0.002). Red blood cell reduced glutathione concentration was positively correlated with the levels of oxidized bases detected by endonuclease III (p= 0.047), heme degradation products (p = 0.015) and hs-CRP (p= 0.020). However, plasma carbonyl levels showed no significant correlation with other markers. The data from the literature and from our very limited study suggest a complex relationship between measures of oxidative stress and frequently used clinical parameters believed to reflect inflammation or oxidative stress. Published by Elsevier B.V.
C1 [Trzeciak, Andrzej R.; Jacob, Kimberly D.; Barnes, Janice; Lohani, Althaf; Evans, Michele K.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Mohanty, Joy G.; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
[Zonderman, Alan B.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Ejiogu, Ngozi; Evans, Michele K.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Evans, MK (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM evansmi@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU NIH, National Institute on Aging; National Institute on Minority Healthy
and Health Disparities
FX Endonuclease III was a generous gift from Dr. Andrew R. Collins
(University of Oslo, Oslo, Norway). We thank Drs. Nicole Noren Hooten,
Kotb Abdelmohsen, and Larry J. Brant for valuable discussions. We also
thank nurses Catherine Sackett, Mary Sam-Nwoha, and Patricia
Julien-Williams who work in the HANDLS study for their careful
assessment of the participants and the acquisition of clinical samples.
This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging and the National Institute on Minority
Healthy and Health Disparities.
NR 49
TC 15
Z9 15
U1 1
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD AUG 1
PY 2012
VL 736
IS 1-2
SI SI
BP 93
EP 103
DI 10.1016/j.mrfmmm.2012.01.002
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 999BK
UT WOS:000308283900013
PM 22273780
ER
PT J
AU Saribasak, H
Gearhart, PJ
AF Saribasak, Huseyin
Gearhart, Patricia J.
TI Does DNA repair occur during somatic hypermutation?
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE Activation-induced deaminase; Base excision repair; Mismatch repair; DNA
polymerases
ID CLASS-SWITCH RECOMBINATION; INDUCED CYTIDINE DEAMINASE; IMMUNOGLOBULIN
GENE HYPERMUTATION; BASE EXCISION-REPAIR; ACTIVATION-INDUCED DEAMINASE;
SINGLE-STRANDED-DNA; POLYMERASE-ETA; ANTIBODY DIVERSIFICATION; VARIABLE
GENES; MICE DEFICIENT
AB Activation-induced deaminase (AID) initiates a flood of DNA damage in the immunoglobulin loci, leading to abasic sites, single-strand breaks and mismatches. It is compelling that some proteins in the canonical base excision and mismatch repair pathways have been hijacked to increase mutagenesis during somatic hypermutation. Thus, the AID-induced mutagenic pathways involve a mix of DNA repair proteins and low fidelity DNA polymerases to create antibody diversity. In this review, we analyze the roles of base excision repair, mismatch repair, and mutagenesis during somatic hypermutation of rearranged variable genes. The emerging view is that faithful base excision repair occurs simultaneously with mutagenesis, whereas faithful mismatch repair is mostly absent. Published by Elsevier Ltd.
C1 [Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 6C220, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
RI Saribasak, Huseyin/C-9331-2012
OI Saribasak, Huseyin/0000-0003-0055-062X
FU Intramural Research Program of the NIH, National Institute on Aging
FX We thank Robert Maul, Kimberly Zanotti, and Nagarama Kothapalli for
valuable comments. This work was supported entirely by the Intramural
Research Program of the NIH, National Institute on Aging.
NR 99
TC 20
Z9 21
U1 1
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD AUG
PY 2012
VL 24
IS 4
BP 287
EP 292
DI 10.1016/j.smim.2012.05.002
PG 6
WC Immunology
SC Immunology
GA 995YW
UT WOS:000308052200007
PM 22728014
ER
PT J
AU Farci, P
Niro, GA
AF Farci, Patrizia
Niro, Grazia Anna
TI Clinical Features of Hepatitis D
SO SEMINARS IN LIVER DISEASE
LA English
DT Review
DE hepatitis D virus; acute hepatitis D; chronic hepatitis D; cirrhosis;
hepatocellular carcinoma; clinical features; liver pathology; viral
interaction
ID B SURFACE-ANTIGEN; DELTA VIRUS-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS;
LIVER FIBROSIS PROGRESSION; C-VIRUS; HEPATOCELLULAR-CARCINOMA;
FULMINANT-HEPATITIS; TRIPLE INFECTION; VIROLOGICAL PROFILES; COINFECTED
PATIENTS
AB Hepatitis D is caused by infection with hepatitis D virus (HDV), a defective RNA virus that requires the obligatory helper function of hepatitis B virus (HBV) for its in vivo transmission. Thus, HDV is acquired only by coinfection with HBV or by superinfection of an HBV carrier. The clinical outcome of hepatitis D differs according to the modality of infection. Whereas coinfection evolves to chronicity in only 2% of the cases, superinfection results in chronic infection in over 90% of the cases. HDV is a highly pathogenic virus that causes acute, often fulminant hepatitis, as well as a rapidly progressive form of chronic viral hepatitis, leading to cirrhosis in 70 to 80% of the cases. The clinical picture of HDV disease is evolving as a consequence of a significant change in the epidemiology of HDV infection, which has led to a significant decline in incidence in Western countries, mainly as a result of universal HBV vaccination programs. However, in the face of a declining prevalence in areas of old endemicity like Europe, immigration poses a threat of HDV resurgence. The interaction of HDV with other hepatitis viruses or human immunodeficiency virus is complex and may lead to different patterns in terms of virologic expression and immunologic responses. Multiple viral infections are associated with rapid progression of liver fibrosis and eventually with the development of hepatocellular carcinoma. Hepatitis D is not a vanishing disease, and continuous efforts should be made to improve its prevention and treatment.
C1 [Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Niro, Grazia Anna] IRCCS, Casa Sollievo Sofferenza Hosp, Div Gastroenterol, Foggia, Italy.
RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 50 South Dr,MSC 8009,Bldg 50,Room 6529, Bethesda, MD 20892 USA.
EM pfarci@niaid.nih.gov
RI Niro, Grazia/Q-9087-2016;
OI Niro, Grazia/0000-0002-6169-9586; Bossa, Fabrizio/0000-0002-4518-9949
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD
FX Patrizia Farci is supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD.
NR 81
TC 22
Z9 23
U1 0
U2 7
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
EI 1098-8971
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD AUG
PY 2012
VL 32
IS 3
BP 228
EP 236
DI 10.1055/s-0032-1323628
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 996CQ
UT WOS:000308062100006
PM 22932971
ER
PT J
AU Migliaccio, A
Castoria, G
de Falco, A
Bilancio, A
Giovannelli, P
Di Donato, M
Marino, I
Yamaguchi, H
Appella, E
Auricchio, F
AF Migliaccio, Antimo
Castoria, Gabriella
de Falco, Antonietta
Bilancio, Antonio
Giovannelli, Pia
Di Donato, Marzia
Marino, Irene
Yamaguchi, Hiroshi
Appella, Ettore
Auricchio, Ferdinando
TI Polyproline and Tat transduction peptides in the study of the rapid
actions of steroid receptors
SO STEROIDS
LA English
DT Article; Proceedings Paper
CT 7th International Meeting on Rapid Responses to Steroid Hormones (RRSH)
CY SEP 14-17, 2011
CL Crete, GREECE
DE Androgen receptor; Estrogen receptor; Rapid action; Nuclear export;
Peptides
ID ESTRADIOL-RECEPTOR; ESTROGEN-RECEPTOR; PROTEIN INTERACTIONS; ANDROGEN
RECEPTOR; NUCLEAR EXPORT; CANCER CELLS; SH3 DOMAIN; SRC; GROWTH; BREAST
AB Cellular responses to signals require the action of a myriad of protein networks, which are regulated by protein/protein associations [1]. Rapid actions of steroid hormones are also subject to this regulation. They induce direct association of steroid receptors with different proteins (e.g., growth factor receptors, signaling effectors, scaffold proteins, transcription factors). These multi-molecular complexes drive signaling activation and finally trigger basic hormonal effects. Receptor/protein associations are attracting increased interest concerning their role in hormone action as well as their potential use as therapeutic targets in hormonal diseases. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Migliaccio, Antimo; Castoria, Gabriella; de Falco, Antonietta; Bilancio, Antonio; Giovannelli, Pia; Di Donato, Marzia; Marino, Irene; Auricchio, Ferdinando] Univ Naples 2, Dept Gen Pathol, I-80138 Naples, Italy.
[Yamaguchi, Hiroshi; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Auricchio, F (reprint author), Univ Naples 2, Dept Gen Pathol, Via L De Crecchio 7, I-80138 Naples, Italy.
EM ferdinando.auricchio@unina2.it
OI BILANCIO, Antonio/0000-0002-5118-3359; Di Donato,
Marzia/0000-0001-7207-826X; Castoria, Gabriella/0000-0002-0576-4494;
Migliaccio, Antimo/0000-0002-4197-2055
FU Associazione Italiana per la Ricerca sul Cancro
NR 24
TC 4
Z9 4
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-128X
J9 STEROIDS
JI Steroids
PD AUG
PY 2012
VL 77
IS 10
SI SI
BP 974
EP 978
DI 10.1016/j.steroids.2012.01.014
PG 5
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 990FS
UT WOS:000307617000014
PM 22306578
ER
PT J
AU Gopal, DM
Kalogeropoulos, AP
Georgiopoulou, VV
Smith, AL
Bauer, DC
Newman, AB
Kim, L
Bibbins-Domingo, K
Tindle, H
Harris, TB
Tang, WWH
Kritchevsky, SB
Butler, J
AF Gopal, Deepa M.
Kalogeropoulos, Andreas P.
Georgiopoulou, Vasiliki V.
Smith, Andrew L.
Bauer, Douglas C.
Newman, Anne B.
Kim, Lauren
Bibbins-Domingo, Kirsten
Tindle, Hillary
Harris, Tamara B.
Tang, Wilson W. H.
Kritchevsky, Stephen B.
Butler, Javed
TI Cigarette smoking exposure and heart failure risk in older adults: The
Health, Aging, and Body Composition Study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; INCIDENT HYPERTENSION; COMPETING RISK;
MORTALITY; SMOKERS; WOMEN; DYSFUNCTION; CESSATION; MARKERS; EVENTS
AB Background Although there is evidence linking smoking and heart failure (HF), the association between lifetime smoking exposure and HF in older adults and the strength of this association among current and past smokers is not well known.
Methods We examined the association between smoking status, pack-years of exposure, and incident HF risk in 2,125 participants of the Health, Aging, and Body Composition Study (age 73.6 +/- 2.9 years, 69.7% women, 54.2% whites) using proportional hazard models.
Results At inception, 54.8% of participants were nonsmokers, 34.8% were past smokers, and 10.4% were current smokers. During follow-up (median 9.4 years), HF incidence was 11.4 per 1,000 person-years in nonsmokers, 15.2 in past smokers (hazard ratio [HR] vs nonsmokers 1.33, 95% CI 1.01-1.76, P = .045), and 21.9 in current smokers (HR 1.93, 95% CI 1.30-2.84, P = .001). After adjusting for HF risk factors, incident coronary events, and competing risk for death, a dose-effect association between pack-years of exposure and HF risk was observed (HR 1.09, 95% CI 1.05-1.14, P < .001 per 10 pack-years). Heart failure risk was not modulated by pack-years of exposure in current smokers. In past smokers, HR for HF was 1.05 (95% CI 0.64-1.72) for 1 to 11 pack-years, 1.23 (95% CI 0.82-1.83) for 12 to 35 pack-years, and 1.64 (95% CI 1.11-2.42) for > 35 pack-years of exposure in fully adjusted models (P < .001 for trend) compared with nonsmokers.
Conclusions In older adults, both current and past cigarette smoking increase HF risk. In current smokers, this risk is high irrespective of pack-years of exposure, whereas in past smokers, there was a dose-effect association. (Am Heart J 2012; 164: 236-42.)
C1 [Gopal, Deepa M.] Boston Univ, Boston, MA 02215 USA.
[Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Smith, Andrew L.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
[Bauer, Douglas C.; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.; Tindle, Hillary] Univ Pittsburgh, Pittsburgh, PA USA.
[Kim, Lauren; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Tang, Wilson W. H.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
RP Butler, J (reprint author), Emory Cardiovasc Clin Res Inst, 1462 Clifton Rd NE,Suite 504, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Newman, Anne/C-6408-2013; Kalogeropoulos, Andreas/A-9494-2009;
OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos,
Andreas/0000-0002-1284-429X; Gopal, Deepa/0000-0003-3534-9360;
Kritchevsky, Stephen/0000-0003-3336-6781
FU NCI NIH HHS [R01 CA141596]; NIA NIH HHS [N01 AG062106, R01 AG028050];
NIAMS NIH HHS [K24 AR051895]; NINR NIH HHS [R01 NR012459]
NR 35
TC 18
Z9 18
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2012
VL 164
IS 2
BP 236
EP 242
DI 10.1016/j.ahj.2012.05.013
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 991AR
UT WOS:000307673700017
PM 22877810
ER
PT J
AU Choi, EY
Yan, RT
Fernandes, VRS
Opdahl, A
Gomes, AS
Almeida, ALC
Wu, CO
Liu, K
Carr, JJ
McClelland, RL
Bluemke, DA
Lima, JAC
AF Choi, Eui-Young
Yan, Raymond T.
Fernandes, Veronica R. S.
Opdahl, Anders
Gomes, Antoinette S.
Almeida, Andre L. C.
Wu, Colin O.
Liu, Kiang
Carr, Jeffrey J.
McClelland, Robyn L.
Bluemke, David A.
Lima, Joao A. C.
TI High-sensitivity C-reactive protein as an independent predictor of
progressive myocardial functional deterioration: The multiethnic study
of atherosclerosis
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID HEART-FAILURE; RISK; DYSFUNCTION; ARTERIAL; MRI; AGE
AB Background Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure.
Methods Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc.
Results During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, Delta Ecc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052-0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049-0.147, P < .001, model 3).
Conclusion Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease. (Am Heart J 2012; 164: 251-8.)
C1 [Choi, Eui-Young; Yan, Raymond T.; Opdahl, Anders; Almeida, Andre L. C.; Lima, Joao A. C.] Johns Hopkins Univ, Baltimore, MD USA.
[Choi, Eui-Young] Yonsei Univ, Coll Med, Seoul, South Korea.
[Fernandes, Veronica R. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Wu, Colin O.] NHLBI, Bethesda, MD 20892 USA.
[Liu, Kiang] Northwestern Univ, Sch Med, Chicago, IL USA.
[Carr, Jeffrey J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[McClelland, Robyn L.] Univ Washington, Seattle, WA 98195 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Opdahl, Anders/E-2958-2010; Opdahl, Anders/I-7580-2015; Carr,
John/A-1938-2012;
OI Opdahl, Anders/0000-0002-0599-592X; Opdahl, Anders/0000-0002-0599-592X;
Carr, John/0000-0002-4398-8237; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [RO1-HL66075-01]; MESA
[NO1-HC-95162, NO1-HC-95168, NO1-HC-95169]
FX This study was supported by the National Heart, Lung, and Blood
Institute Grant (RO1-HL66075-01) and the MESA study contracts
(NO1-HC-95162, NO1-HC-95168, and NO1-HC-95169).
NR 20
TC 16
Z9 16
U1 0
U2 4
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 AUG
PY 2012
VL 164
IS 2
BP 251
EP 258
DI 10.1016/j.ahj.2012.05.010
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 991AR
UT WOS:000307673700019
PM 22877812
ER
PT J
AU Anderson, AH
Yang, W
Hsu, CY
Joffe, MM
Leonard, MB
Xie, DW
Chen, J
Greene, T
Jaar, BG
Kao, P
Kusek, JW
Landis, JR
Lash, JP
Townsend, RR
Weir, MR
Feldman, HI
AF Anderson, Amanda Hyre
Yang, Wei
Hsu, Chi-yuan
Joffe, Marshall M.
Leonard, Mary B.
Xie, Dawei
Chen, Jing
Greene, Tom
Jaar, Bernard G.
Kao, Patricia
Kusek, John W.
Landis, J. Richard
Lash, James P.
Townsend, Raymond R.
Weir, Matthew R.
Feldman, Harold I.
CA CRIC Study Investigators
TI Estimating GFR Among Participants in the Chronic Renal Insufficiency
Cohort (CRIC) Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Glomerular filtration rate (GFR); kidney function; GFR estimation
ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; SINGLE SUBCUTANEOUS
INJECTION; BASE-LINE CHARACTERISTICS; CREATININE MEASUREMENTS;
KIDNEY-DISEASE; AFRICAN-AMERICAN; BODY-COMPOSITION; PREDICTION;
CLEARANCE
AB Background: Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies.
Study Design: Cross-sectional study of 1,433 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (ie, the GFR subcohort) to derive an internal GFR estimating equation using a split-sample approach.
Setting & Participants: Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black.
Index Test: CRIC GFR estimating equation.
Reference Test or Outcome: Urinary I-125-iothalamate clearance testing (measured GFR [mGFR]).
Other Measurements: Laboratory measures, including serum creatinine and cystatin C, and anthropometrics.
Results: In the validation data set, the model that included serum creatinine level, serum cystatin Clevel, age, sex, and race was the most parsimonious and similarly predictive of mGFR compared with a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, root mean square errors for the separate models were 0.207 versus 0.202, respectively. Performance of the CRIC GFR estimating equation was most accurate for the subgroups of younger participants, men, nonblacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m(2), those with higher 24-hour urine creatinine excretion, those with lower high-sensitivity C-reactive protein levels, and those with higher mGFRs.
Limitations: Urinary clearance of I-125-iothalamate is an imperfect measure of true GFR; cystatin C level is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors.
Conclusions: The CRIC GFR estimating equation predicts mGFR accurately in the CRIC cohort using serum creatinine and cystatin C levels, age, sex, and race. Its performance was best in younger and healthier participants. Am J Kidney Dis. 60(2): 250-261. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Anderson, Amanda Hyre; Yang, Wei; Joffe, Marshall M.; Leonard, Mary B.; Xie, Dawei; Landis, J. Richard; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Hsu, Chi-yuan] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Leonard, Mary B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Chen, Jing] Tulane Univ, Sch Med, Sect Nephrol & Hypertens, New Orleans, LA 70112 USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
[Jaar, Bernard G.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Jaar, Bernard G.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Jaar, Bernard G.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Kao, Patricia] Case Western Reserve Univ, Dept Nephrol & Hypertens, Cleveland, OH 44106 USA.
[Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Lash, James P.] Univ Illinois, Coll Med, Nephrol Sect, Chicago, IL USA.
[Townsend, Raymond R.; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Weir, Matthew R.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
RP Anderson, AH (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 929 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM andersah@mail.med.upenn.edu
RI Yang, Wei/A-9223-2009;
OI Yang, Wei/0000-0001-8984-4389; Landis, J Richard/0000-0001-8099-0988
FU NIDDK [5U01DK060990, 5U01DK060984, 5U01DK061022, 5U01DK061021,
5U01DK061028, 5U01DK060980, 5U01DK060963, 5U01DK060902]; National
Institutes of Health; University of Pennsylvania [UL1 RR-024134,
K01DK092353, L30 DK084815, K24DK002651]; Johns Hopkins University [UL1
RR-025005]; University of Maryland General Clinical Research Center
(GCRC) [M01 RR-16500]; Case Western Reserve University Clinical and
Translational Science [UL1 RR-024989]; University of Michigan [GCRC M01
RR-000042, CTSA UL1 RR-024986]; University of Illinois at Chicago
Clinical Research Center [UL1 RR-029879, M01 RR-013987-06];
Tulane/LSU/Charity Hospital [GCRC M01 RR-05096]; Kaiser NIH/NCRR
UCSF-CTSI [UL1 RR-024131]; Clinical Translational Science Awards (CTSA)
FX In addition to funding under a cooperative agreement from NIDDK
(5U01DK060990, 5U01DK060984, 5U01DK061022, 5U01DK061021, 5U01DK061028,
5U01DK060980, 5U01DK060963, and 5U01DK060902), this work was supported
in part by the following institutional Clinical Translational Science
Awards (CTSA) and other National Institutes of Health grants: University
of Pennsylvania UL1 RR-024134, K01DK092353, L30 DK084815 and
K24DK002651; Johns Hopkins University UL1 RR-025005; University of
Maryland General Clinical Research Center (GCRC) M01 RR-16500; Case
Western Reserve University Clinical and Translational Science
Collaborative (University Hospitals of Cleveland, Cleveland Clinic
Foundation, and Metro-Health) UL1 RR-024989; University of Michigan GCRC
M01 RR-000042 and CTSA UL1 RR-024986; University of Illinois at Chicago
Clinical Research Center UL1 RR-029879 and M01 RR-013987-06;
Tulane/LSU/Charity Hospital GCRC M01 RR-05096; and Kaiser NIH/NCRR
UCSF-CTSI UL1 RR-024131.
NR 39
TC 59
Z9 59
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD AUG
PY 2012
VL 60
IS 2
BP 250
EP 261
DI 10.1053/j.ajkd.2012.04.012
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 974ZW
UT WOS:000306477200013
PM 22658574
ER
PT J
AU Lu, XP
Zhao, XL
Feng, JY
Liou, AP
Anthony, S
Pechhold, S
Sun, YX
Lu, HY
Wank, S
AF Lu, Xinping
Zhao, Xilin
Feng, Jianying
Liou, Alice P.
Anthony, Shari
Pechhold, Susanne
Sun, Yuxiang
Lu, Huiyan
Wank, Stephen
TI Postprandial inhibition of gastric ghrelin secretion by long-chain fatty
acid through GPR120 in isolated gastric ghrelin cells and mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE appetite; metabolism; hormone; regulation
ID LIPOPROTEIN-LIPASE; GROWTH-HORMONE; RAT STOMACH; ACYLATED PEPTIDE;
IN-VITRO; HUMANS; SOMATOSTATIN; EXPRESSION; RECEPTORS; INSULIN
AB Lu X, Zhao X, Feng J, Liou AP, Anthony S, Pechhold S, Sun Y, Lu H, Wank S. Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice. Am J Physiol Gastrointest Liver Physiol 303: G367-G376, 2012. First published June 7, 2012; doi: 10.1152/ajpgi.00541.2011.-Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-gamma. Quantitative RTPCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-gamma in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion.
C1 [Lu, Xinping; Zhao, Xilin; Feng, Jianying; Liou, Alice P.; Anthony, Shari; Wank, Stephen] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Pechhold, Susanne] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA.
[Sun, Yuxiang] Baylor Coll Med, Childrens Nutr Res Ctr, Huffington Ctr Aging, Dept Pediat, Houston, TX 77030 USA.
[Sun, Yuxiang] Baylor Coll Med, Childrens Nutr Res Ctr, Huffington Ctr Aging, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Lu, Huiyan] NIDDKD, Transgen Fac, NIH, Bethesda, MD USA.
RP Wank, S (reprint author), NIDDK, DDB, NIH, 10-9C-101, Bethesda, MD 20892 USA.
EM stevew@mail.nih.gov
NR 45
TC 38
Z9 38
U1 1
U2 4
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 AUG
PY 2012
VL 303
IS 3
BP G367
EP G376
DI 10.1152/ajpgi.00541.2011
PG 10
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 984XU
UT WOS:000307227700010
PM 22678998
ER
PT J
AU Lee, RX
Li, QQ
Reed, E
AF Lee, Rebecca X.
Li, Qingdi Quentin
Reed, Eddie
TI beta-Elemene Effectively Suppresses the Growth and Survival of Both
Platinum-sensitive and -resistant Ovarian Tumor Cells
SO ANTICANCER RESEARCH
LA English
DT Article
DE beta-Elemene; cisplatin resistance; cell cycle arrest; apoptosis;
ovarian cancer; Chinese medicine; A2780; A2780/CP cells; p53;
p21(WAF/CIP1)
ID CANCER-CHEMOTHERAPY; CYCLE ARREST; APOPTOSIS; DEATH; MITOCHONDRIAL;
CHECKPOINTS; CISPLATIN; CHEMOSENSITIVITY; COMBINATION; INHIBITORS
AB The development of cisplatin drug resistance remains a chief concern in ovarian cancer chemotherapy. beta-Elemene is a natural plant product with broad-spectrum antitumor activity towards many types of carcinomas. This study aimed to define the biological and therapeutic significance of beta-elemene in chemoresistant ovarian cancer. In the present study. beta-elemene significantly inhibited cell growth and proliferation of both the cisplatin-sensitive human ovarian cancer cell line A2780 and its cisplatin-resistant counterpart A2780/CP. beta-Elemene also suppressed the growth of several other chemosensitive and chemoresistant ovarian cancer cell lines, including ES-2 MCAS, OVCAR-3, and SKOV-3, with the half maximal inhibitory concentration (IC50) values ranging from 54 to 78 mu g/ml. In contrast, the IC50 values of beta-elemene for the human ovarian epithelial cell lines IOSE-386 and IOSE-397 were 110 and 114 mu g/ml, respectively, which are almost two-fold those for the ovarian cancer cell lines. Cell cycle analysis demonstrated that beta-elemene induced a persistent block of cell cycle progression at the G(2)/M phase in A2780 and A2780/CP cells. This was mediated by alterations in cyclin and cyclin-dependent kinase expression, including the down-regulation of CDC2, cyclin A, and cyclin B1, and the up-regulation of p21(WAF1/CIP1) and p53 proteins. Moreover, beta-elemene triggered apoptosis and irreversible cell death in both sensitive and resistant ovarian cancer cells via the activation of caspase-3, -8 and 9; the loss of mitochondrial membrane potential (Delta psi m); the release of cytochrome c into the cytosol; and changes in the expression of BCL-2 family proteins. All of these molecular changes were associated with beta-elemene-induced growth inhibition and cell death of ovarian cancer cells. Our results demonstrate that beta-elemene has antitumor activity against both platinum-sensitive and resistant ovarian cancer cells, and thus has the potential for development as a chemotherapeutic agent for cisplatin-resistant ovarian cancer.
C1 [Li, Qingdi Quentin] NIH, Bethesda, MD 20892 USA.
[Lee, Rebecca X.; Li, Qingdi Quentin; Reed, Eddie] W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
RP Li, QQ (reprint author), NIH, Bldg 10,Room 11N234, Bethesda, MD 20892 USA.
EM liquenti@mail.nih.gov
FU National Institutes of Health [P20RR16440-010003, P20RR16440-020003,
P20RR16440-030003, P20RR16440-040003]; West Virginia University School
of Medicine
FX This study was supported by grants from the National Institutes of
Health (Nos. P20RR16440-010003, P20RR16440-020003, P20RR16440-030003,
P20RR16440-040003 to QQL,) and West Virginia University School of
Medicine (to QQL).
NR 45
TC 16
Z9 20
U1 0
U2 2
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD AUG
PY 2012
VL 32
IS 8
BP 3103
EP 3113
PG 11
WC Oncology
SC Oncology
GA 980KS
UT WOS:000306892700012
PM 22843880
ER
PT J
AU Elbaum, DJ
Cowen, EW
AF Elbaum, David J.
Cowen, Edward W.
TI Voriconazole-Associated Phototoxic Effects and Lentigo Formation in an
African American Man
SO ARCHIVES OF DERMATOLOGY
LA English
DT Letter
C1 [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20814 USA.
EM cowene@mail.nih.gov
NR 5
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 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD AUG
PY 2012
VL 148
IS 8
BP 965
EP 966
PG 3
WC Dermatology
SC Dermatology
GA 991YP
UT WOS:000307740500027
PM 22911208
ER
PT J
AU Shumway, S
Farmer, C
Thurm, A
Joseph, L
Black, D
Golden, C
AF Shumway, Stacy
Farmer, Cristan
Thurm, Audrey
Joseph, Lisa
Black, David
Golden, Christine
TI The ADOS Calibrated Severity Score: Relationship to Phenotypic Variables
and Stability over Time
SO AUTISM RESEARCH
LA English
DT Article
DE autism diagnostic observation schedule (ADOS); autism spectrum
disorders; severity; diagnosis
ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; VALIDITY;
CHILDREN; AGE
AB Measurement of the severity of autism at a single time point, and over time, is a widespread challenge for researchers. Recently, Gotham, Pickles, and Lord published a severity metric (calibrated severity scores; CSS) that takes into account age and language level and is based on raw total scores of the Autism Diagnostic Observation Schedule (ADOS), a standardized measure commonly used in autism diagnosis. The present study examined psychometric characteristics of the CSS compared to raw scores in an independent sample of 368 children aged 2 to 12 years with autism, pervasive developmental disorder-not otherwise specified (PDD-NOS), non-spectrum delay, or typical development. Reflecting the intended calibration, the CSS were more uniformly distributed within clinical diagnostic category and across ADOS modules than were raw scores. Cross-sectional analyses examining raw and severity scores and their relationships to participant characteristics revealed that verbal developmental level was a significant predictor of raw score but accounted for significantly less variance in the CSS. Longitudinal analyses indicated overall stability of the CSS over 12 to 24 months in children with autism. Findings from this study support the use of the CSS as a more valid indicator of autism severity than the ADOS raw total score, and extend the literature by examining the stability over 12 to 24 months of the CSS in children with ASD. Autism Res 2012, 5: 267276. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
C1 [Shumway, Stacy; Farmer, Cristan; Thurm, Audrey; Joseph, Lisa; Black, David; Golden, Christine] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
RP Farmer, C (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1C250, Bethesda, MD 20892 USA.
EM farmerca@mail.nih.gov
OI Manwaring, Stacy/0000-0002-0835-9398
FU National Institute of Mental Health (NIMH)
FX This research was supported by the Intramural Program of the National
Institute of Mental Health (NIMH). The views expressed in this paper do
not necessarily represent the views of the NIMH, NIH, HHS, or the United
Stated Government. The authors extend their gratitude for the children
and their families who volunteered their time and efforts during the
research.
NR 28
TC 21
Z9 21
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-3792
J9 AUTISM RES
JI Autism Res.
PD AUG
PY 2012
VL 5
IS 4
BP 267
EP 276
DI 10.1002/aur.1238
PG 10
WC Behavioral Sciences; Psychology, Developmental
SC Behavioral Sciences; Psychology
GA 991WF
UT WOS:000307733300005
PM 22628087
ER
PT J
AU VanderWalde, A
Ye, W
Frankel, P
Asuncion, D
Leong, L
Luu, T
Morgan, R
Twardowski, P
Koczywas, M
Pezner, R
Paz, IB
Margolin, K
Wong, J
Doroshow, JH
Forman, S
Shibata, S
Somlo, G
AF VanderWalde, A.
Ye, W.
Frankel, P.
Asuncion, D.
Leong, L.
Luu, T.
Morgan, R.
Twardowski, P.
Koczywas, M.
Pezner, R.
Paz, I. B.
Margolin, K.
Wong, J.
Doroshow, J. H.
Forman, S.
Shibata, S.
Somlo, G.
TI Long-Term Survival after High-Dose Chemotherapy Followed by Peripheral
Stem Cell Rescue for High-Risk, Locally Advanced/Inflammatory, and
Metastatic Breast Cancer
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE High-dose chemotherapy; Autologous peripheral blood transplantation;
Adjuvant therapy; High-risk breast cancer
ID CONVENTIONAL ADJUVANT CHEMOTHERAPY; PHASE-III TRIAL; RANDOMIZED-TRIAL;
LYMPH-NODES; PROGNOSTIC INDICATORS; MARROW SUPPORT; TRANSPLANTATION;
THERAPY; WOMEN; CONSOLIDATION
AB Patients with high-risk locally advanced/inflammatory and oligometastatic (<= 3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% Cl, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials. Biol Blood Marrow Transplant 18: 1273-1280 (2012) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [VanderWalde, A.; Leong, L.; Luu, T.; Morgan, R.; Twardowski, P.; Koczywas, M.; Shibata, S.; Somlo, G.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA.
[Ye, W.; Frankel, P.] City Hope Comprehens Canc Ctr, Dept Informat Sci, Duarte, CA USA.
[Pezner, R.; Wong, J.] City Hope Comprehens Canc Ctr, Dept Radiat Oncol, Duarte, CA USA.
[Paz, I. B.] City Hope Comprehens Canc Ctr, Dept Gen Oncol Surg, Duarte, CA USA.
[Asuncion, D.] Kaiser Permanente, Med Oncol & Hematol, Irvine, CA USA.
[Margolin, K.] Seattle Canc Care Alliance, Seattle, WA USA.
[Doroshow, J. H.] Natl Canc Ctr, Div Canc Treatment, Bethesda, MD USA.
RP Somlo, G (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM gsomlo@coh.org
FU Amgen; Bristol-Myers Squibb; National Institutes of Health [M01 RR00043,
CA 33572]
FX This work was supported by grants from Amgen and Bristol-Myers Squibb,
and by grants from the National Institutes of Health (M01 RR00043 and CA
33572). George Somlo received research support for this project from
Amgen and Bristol-Myers Squibb. A. VanderWalde had no relationships to
disclose throughout the research and preparation of the manuscript, but
has since become employed by Amgen. All other authors report no
conflicts of interest.
NR 48
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD AUG
PY 2012
VL 18
IS 8
BP 1273
EP 1280
DI 10.1016/j.bbmt.2012.01.021
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 982KB
UT WOS:000307040800017
PM 22306735
ER
PT J
AU Battiwalla, M
Ellis, K
Li, PG
Pavletic, SZ
Akpek, G
Hematti, P
Klumpp, TR
Maziarz, RT
Savani, BN
Aljurf, MD
Cairo, MS
Drobyski, WR
George, B
Hahn, T
Khera, N
Litzow, MR
Loren, AW
Saber, W
Arora, M
Urbano-Ispizua, A
Cutler, C
Flowers, MED
Spellman, SR
AF Battiwalla, Minoo
Ellis, Kristin
Li, Peigang
Pavletic, Steven Z.
Akpek, Gorgun
Hematti, Peiman
Klumpp, Thomas R.
Maziarz, Richard T.
Savani, Bipin N.
Aljurf, Mahmoud D.
Cairo, Mitchell S.
Drobyski, William R.
George, Biju
Hahn, Theresa
Khera, Nandita
Litzow, Mark R.
Loren, Alison W.
Saber, Wael
Arora, Mukta
Urbano-Ispizua, Alvaro
Cutler, Corey
Flowers, Mary E. D.
Spellman, Stephen R.
TI HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or
Survival in HLA-Matched Sibling Transplantation for Hematologic
Malignancies
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE DR15; Hematopoietic stem cell transplantation (HSCT); GVHD; Survival;
graft-versus-lymphoma
ID APLASTIC-ANEMIA PATIENTS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; STEM-CELL
TRANSPLANTATION; REDUCED RELAPSE RATE; IMMUNOSUPPRESSIVE THERAPY;
MYELODYSPLASTIC SYNDROME; INCREASED FREQUENCY; POPULATION; HLA-DR15; DR2
AB The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from MLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning. T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRBI*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS. Biol Blood Marrow Transplant 18: 1302-1308 (2012) Published by Elsevier Inc on behalf of American Society for Blood and Mal-row Transplantation
C1 [Battiwalla, Minoo] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA.
[Ellis, Kristin; Li, Peigang; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA.
[Akpek, Gorgun] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Hematti, Peiman] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Klumpp, Thomas R.] Temple Bone Marrow Transplant Program, Philadelphia, PA USA.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia.
[Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA.
[George, Biju] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India.
[Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Khera, Nandita; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Loren, Alison W.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
[Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
RP Battiwalla, M (reprint author), NHLBI, NIH, Hematol Branch, 10-CRC,Rm 5-3581,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM minoo.battiwalla@nih.gov
FU National Institute of Health (NIH) intramural research programs of the
NHLBI; NCI; Public Health Service from the National Cancer Institute
(NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI)
[5U01HL069294]; National Institute of Allergy and Infectious Diseases
(NIAID); Health Resources and Services Administration (HRSA/DHHS)
[HHSH234200637015C]; Office of Naval Research [N00014-10-1-0204,
N00014-1-1-0339]; Altos, Inc.; Amgen, Inc.; Angioblast; Ariad; Be the
Match Foundation; Blue Cross and Blue Shield Association; Buchanan
Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH;
Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma
Society; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.;
Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor
Program; OptumHealth Care Solutions, Inc.; Otsuka America
Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals;
Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; Wellpoint,
Inc.
FX This work was supported by the National Institute of Health (NIH)
intramural research programs of the NHLBI and NCI. CIBMTR is supported
by Public Health Service Grant/Cooperative Agreement U24-CA76518 from
the National Cancer Institute (NCI), the National Heart, Lung and Blood
Institute (NHLBI) and the National Institute of Allergy and Infectious
Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI
and NCI; a contract HHSH234200637015C with Health Resources and Services
Administration (HRSA/DHHS); two grants N00014-10-1-0204 and
N00014-1-1-0339 from the Office of Naval Research; and grants from
Altos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical
College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and
Blue Shield Association; Buchanan Family Foundation; CaridianBCT;
Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research
Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva
Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation;
GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The
Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman
USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program;
OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.;
Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish
Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc.
NR 25
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD AUG
PY 2012
VL 18
IS 8
BP 1302
EP 1308
DI 10.1016/j.bbmt.2012.02.011
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 982KB
UT WOS:000307040800021
PM 22414493
ER
PT J
AU Song, LX
Mishel, M
Bensen, JT
Chen, RC
Knafl, GJ
Blackard, B
Farnan, L
Fontham, E
Su, LJ
Brennan, CS
Mohler, JL
Godley, PA
AF Song, Lixin
Mishel, Merle
Bensen, Jeannette T.
Chen, Ronald C.
Knafl, George J.
Blackard, Bonny
Farnan, Laura
Fontham, Elizabeth
Su, L. Joseph
Brennan, Christine S.
Mohler, James L.
Godley, Paul A.
TI How does health literacy affect quality of life among men with newly
diagnosed clinically localized prostate cancer?
SO CANCER
LA English
DT Article
DE health literacy; quality of life; education; race; localized prostate
cancer; PCaP
ID RACIAL-DIFFERENCES; OUTCOMES; STAGE; POPULATION; CARCINOMA; SURVIVORS;
RACE
AB BACKGROUND: Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health-related quality of life (HRQOL) and health literacy among men with prostate cancer. METHODS: Data analysis included 1581 men with newly diagnosed clinically localized prostate cancer from a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). Participants completed assessment of health literacy using Rapid Estimate of Adult Literacy in Medicine (REALM) and HRQOL using the Short Form-12 General Health Survey (SF12). Bivariate and multivariate regression was used to determine the potential association between REALM and HRQOL, while controlling for sociodemographic and illness-related variables. RESULTS: Higher health literacy level was significantly associated with better mental well-being (SF12-Mental Component Summary [MCS]; P < .001) and physical well-being (SF12-Physical Component Summary [PCS]; P < .001) in bivariate analyses. After controlling for sociodemographic (age, marital status, race, income, and education) and illness-related factors (types of cancer treatment, tumor aggressiveness, and comorbidities), health literacy remained significantly associated with SF12-MCS scores (P < .05) but not with SF12-PCS scores. CONCLUSIONS: Among patients with newly diagnosed localized prostate cancer, those with low health literacy levels were more vulnerable to mental distress than those with higher health literacy levels, but physical well-being was no different. These findings suggest that health literacy may be important in patients managing prostate cancer and the effects of treatment, and provide the hypothesis that supportive interventions targeting patients with lower health literacy may improve their HRQOL. Cancer 2012. (C) 2011 American Cancer Society.
C1 [Song, Lixin; Mishel, Merle; Knafl, George J.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA.
[Song, Lixin; Bensen, Jeannette T.; Chen, Ronald C.; Blackard, Bonny; Farnan, Laura; Mohler, James L.; Godley, Paul A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Bensen, Jeannette T.; Godley, Paul A.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Chen, Ronald C.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
[Chen, Ronald C.; Godley, Paul A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA.
[Fontham, Elizabeth; Brennan, Christine S.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA.
[Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
[Godley, Paul A.] Univ N Carolina, Sch Med, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
RP Song, LX (reprint author), Univ N Carolina, Sch Nursing, Carrington Hall, Chapel Hill, NC 27599 USA.
EM lsong@unc.edu
FU Department of Defense [DAMD 17-03-2-0052]
FX The North Carolina-Louisiana Prostate Cancer Project (PCaP) is carried
out as a collaborative study supported by Department of Defense contract
DAMD 17-03-2-0052.
NR 38
TC 14
Z9 15
U1 3
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 1
PY 2012
VL 118
IS 15
BP 3842
EP 3851
DI 10.1002/cncr.26713
PG 10
WC Oncology
SC Oncology
GA 977NU
UT WOS:000306671300023
PM 22180041
ER
PT J
AU Demark-Wahnefried, W
Platz, EA
Ligibel, JA
Blair, CK
Courneya, KS
Meyerhardt, JA
Ganz, PA
Rock, CL
Schmitz, KH
Wadden, T
Philip, EJ
Wolfe, B
Gapstur, SM
Ballard-Barbash, R
McTiernan, A
Minasian, L
Nebeling, L
Goodwin, PJ
AF Demark-Wahnefried, Wendy
Platz, Elizabeth A.
Ligibel, Jennifer A.
Blair, Cindy K.
Courneya, Kerry S.
Meyerhardt, Jeffrey A.
Ganz, Patricia A.
Rock, Cheryl L.
Schmitz, Kathryn H.
Wadden, Thomas
Philip, Errol J.
Wolfe, Bruce
Gapstur, Susan M.
Ballard-Barbash, Rachel
McTiernan, Anne
Minasian, Lori
Nebeling, Linda
Goodwin, Pamela J.
TI The Role of Obesity in Cancer Survival and Recurrence
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
ID BODY-MASS INDEX; STAGE BREAST-CANCER; III COLON-CANCER; GROWTH-FACTOR-I;
RANDOMIZED CONTROLLED-TRIAL; TREATMENT-RELATED TOXICITY; LIFE-STYLE
INTERVENTION; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; PROSTATE-CANCER
AB Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, "The Role of Obesity in Cancer Survival and Recurrence"; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidermal Biomarkers Prev; 21(8); 1244-59. (c) 2012 AACR.
C1 [Demark-Wahnefried, Wendy; Blair, Cindy K.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Courneya, Kerry S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Rock, Cheryl L.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Schmitz, Kathryn H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Wadden, Thomas] Univ Penn, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA.
[Philip, Errol J.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA.
[Wolfe, Bruce] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA.
[Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Bethesda, MD 20892 USA.
[Nebeling, Linda] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada.
RP Demark-Wahnefried, W (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd,Room 346, Birmingham, AL 35294 USA.
EM demark@uab.edu
RI Goodwin, Pamela/K-1477-2013
FU Nutrisystem; [CA13148]; [CA148791]; [CA047888]
FX T. Wadden is a recipient of commercial research grant from Nutrisystem
and is also a consultant and an advisory board member of Novo Nordisk
and Orexigen. E.J. Philip is a consultant and an advisory board member
of Kantar Health. A. McTiernan has ownership interest (including
patents) in Merck and is a consultant and an advisory board member of
Metagenics.; The work was supported by the following grants: CA13148 (W.
Demark-Wahnefried), CA148791 (C.L. Rock, W. Demark-Wahnefried), and
CA047888 (C.K. Blair)
NR 144
TC 79
Z9 81
U1 3
U2 25
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 AUG
PY 2012
VL 21
IS 8
BP 1244
EP 1259
DI 10.1158/1055-9965.EPI-12-0485
PG 16
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 987RC
UT WOS:000307433800003
PM 22695735
ER
PT J
AU Shebl, FM
Cabo-Ramos, DE
Graubard, BI
McGlynn, KA
Altekruse, SF
AF Shebl, Fatma M.
Cabo-Ramos, David E.
Graubard, Barry I.
McGlynn, Katherine A.
Altekruse, Sean F.
TI Socioeconomic Status and Hepatocellular Carcinoma in the United States
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CHRONIC LIVER-DISEASE; CANCER INCIDENCE; VIRUS-INFECTION; MORTALITY;
RISK; EPIDEMIOLOGY; DISPARITIES; POPULATION; PREVALENCE; CALIFORNIA
AB Background: Hepatocellular carcinoma (HCC) has a poor prognosis and, unlike most cancers, HCC incidence and mortality rates are increasing in the United States. While risk is known to vary among different racial and ethnic groups, less is known about the variability of risk within these groups by neighborhood socioeconomic status (SES).
Methods: HCC cases diagnosed in the Surveillance, Epidemiology and End Results (SEER) 11 cancer registries between 1996 and 2007, and the population of the SEER 11 catchment areas was studied. Analyses were conducted to compare census tract area family poverty, educational attainment, and unemployment by race and ethnicity. A multiple linear regression model, weighted by the number of cases and the number of individuals in each census tract, with adjustment for registry, was used to calculate mean differences in area-level attributes between HCC cases and the population.
Results: HCC cases in most racial/ethnic groups had lower mean neighborhood-level measures of SES than their referent population. An exception was seen among Hispanics. Comparing white cases with cases of other racial groups and to Hispanics, white cases lived in neighborhoods with less family poverty, fewer high-school dropouts, and lower unemployment. Compared with white cases, Asian and Pacific Islander and Hispanic cases lived in neighborhoods with a higher percentage of foreign-born population.
Conclusions: Low neighborhood-level SES and immigrant status may be associated with greater risk of HCC within specific racial and ethnic groups.
Impact: These findings could help to focus control resources for HCC toward the most affected communities. Cancer Epidemiol Biomarkers Prev; 21(8); 1330-5. (c) 2012 AACR.
C1 [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Shebl, Fatma M.; Cabo-Ramos, David E.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Room 5003, Rockville, MD 20852 USA.
EM altekrusesf@mail.nih.gov
FU National Cancer Institute; DCCPS; SRP Contracts; SEER Registries
[HHSN261200900022C]; Information Management Services (Biomedical
Computing Support); Intramural Research Program NIH, National Cancer
Institute
FX This study was supported by National Cancer Institute, DCCPS, SRP
Contracts with SEER Registries, Contract HHSN261200900022C with
Information Management Services (Biomedical Computing Support), and the
Intramural Research Program NIH, National Cancer Institute.
NR 44
TC 18
Z9 18
U1 2
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2012
VL 21
IS 8
BP 1330
EP 1335
DI 10.1158/1055-9965.EPI-12-0124
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 987RC
UT WOS:000307433800011
PM 22669949
ER
PT J
AU Ding, YC
McGuffog, L
Healey, S
Friedman, E
Laitman, Y
Shani-Paluch-Shimon
Kaufman, B
Liljegren, A
Lindblom, A
Olsson, H
Kristoffersson, U
Stenmark-Askmalm, M
Melin, B
Domchek, SM
Nathanson, KL
Rebbeck, TR
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Gronwald, J
Huzarski, T
Cybulski, C
Byrski, T
Osorio, A
Cajal, TR
Stavropoulou, AV
Benitez, J
Hamann, U
Rookus, M
Aalfs, CM
de Lange, JL
Meijers-Heijboer, HEJ
Oosterwijk, JC
van Asperen, CJ
Garcia, EBG
Hoogerbrugge, N
Jager, A
van der Luijt, RB
Easton, DF
Peock, S
Frost, D
Ellis, SD
Platte, R
Fineberg, E
Evans, DG
Lalloo, F
Izatt, L
Eeles, R
Adlard, J
Davidson, R
Eccles, D
Cole, T
Cook, J
Brewer, C
Tischkowitz, M
Godwin, AK
Pathak, H
Stoppa-Lyonnet, D
Sinilnikova, OM
Mazoyer, S
Barjhoux, L
Leone, M
Gauthier-Villars, M
Caux-Moncoutier, V
de Pauw, A
Hardouin, A
Berthet, P
Dreyfus, H
Ferrer, SF
Collonge-Rame, MA
Sokolowska, J
Buys, S
Daly, M
Miron, A
Terry, MB
Chung, W
John, EM
Southey, M
Goldgar, D
Singer, CF
Tea, MKM
Gschwantler-Kaulich, D
Fink-Retter, A
Hansen, TVO
Ejlertsen, B
Johannsson, OT
Offit, K
Sarrel, K
Gaudet, MM
Vijai, J
Robson, M
Piedmonte, MR
Andrews, L
Cohn, D
DeMars, LR
DiSilvestro, P
Rodriguez, G
Toland, AE
Montagna, M
Agata, S
Imyanitov, E
Isaacs, C
Janavicius, R
Lazaro, C
Blanco, I
Ramus, SJ
Sucheston, L
Karlan, BY
Gross, J
Ganz, PA
Beattie, MS
Schmutzler, RK
Wappenschmidt, B
Meindl, A
Arnold, N
Niederacher, D
Preisler-Adams, S
Gadzicki, D
Varon-Mateeva, R
Deissler, H
Gehrig, A
Sutter, C
Kast, K
Nevanlinna, H
Aittomaki, K
Simard, J
Spurdle, AB
Beesley, J
Chen, XQ
Tomlinson, GE
Weitzel, J
Garber, JE
Olopade, OI
Rubinstein, WS
Tung, N
Blum, JL
Narod, SA
Brummel, S
Gillen, DL
Lindor, N
Fredericksen, Z
Pankratz, VS
Couch, FJ
Radice, P
Peterlongo, P
Greene, MH
Loud, JT
Mai, PL
Andrulis, IL
Glendon, G
Ozcelik, H
Gerdes, AM
Thomassen, M
Jensen, UB
Skytte, AB
Caligo, MA
Lee, A
Chenevix-Trench, G
Antoniou, AC
Neuhausen, SL
AF Ding, Yuan C.
McGuffog, Lesley
Healey, Sue
Friedman, Eitan
Laitman, Yael
Shani-Paluch-Shimon
Kaufman, Bella
Liljegren, Annelie
Lindblom, Annika
Olsson, Hakan
Kristoffersson, Ulf
Stenmark-Askmalm, Marie
Melin, Beatrice
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy R.
Jakubowska, Anna
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Gronwald, Jacek
Huzarski, Tomasz
Cybulski, Cezary
Byrski, Tomasz
Osorio, Ana
Ramony Cajal, Teresa
Stavropoulou, Alexandra V.
Benitez, Javier
Hamann, Ute
Rookus, Matti
Aalfs, Cora M.
de Lange, Judith L.
Meijers-Heijboer, Hanne E. J.
Oosterwijk, Jan C.
van Asperen, Christi J.
Garcia, Encarna B. Gomez
Hoogerbrugge, Nicoline
Jager, Agnes
van der Luijt, Rob B.
Easton, Douglas F.
Peock, Susan
Frost, Debra
Ellis, Steve D.
Platte, Radka
Fineberg, Elena
Evans, D. Gareth
Lalloo, Fiona
Izatt, Louise
Eeles, Ros
Adlard, Julian
Davidson, Rosemarie
Eccles, Diana
Cole, Trevor
Cook, Jackie
Brewer, Carole
Tischkowitz, Marc
Godwin, Andrew K.
Pathak, Harsh
Stoppa-Lyonnet, Dominique
Sinilnikova, Olga M.
Mazoyer, Sylvie
Barjhoux, Laure
Leone, Melanie
Gauthier-Villars, Marion
Caux-Moncoutier, Virginie
de Pauw, Antoine
Hardouin, Agnes
Berthet, Pascaline
Dreyfus, Helene
Ferrer, Sandra Fert
Collonge-Rame, Marie-Agnes
Sokolowska, Johanna
Buys, Saundra
Daly, Mary
Miron, Alex
Terry, Mary Beth
Chung, Wendy
John, Esther M.
Southey, Melissa
Goldgar, David
Singer, Christian F.
Tea, Muy-Kheng Maria
Gschwantler-Kaulich, Daphne
Fink-Retter, Anneliese
Hansen, Thomas V. O.
Ejlertsen, Bent
Johannsson, Oskar T.
Offit, Kenneth
Sarrel, Kara
Gaudet, Mia M.
Vijai, Joseph
Robson, Mark
Piedmonte, Marion R.
Andrews, Lesley
Cohn, David
DeMars, Leslie R.
DiSilvestro, Paul
Rodriguez, Gustavo
Toland, Amanda Ewart
Montagna, Marco
Agata, Simona
Imyanitov, Evgeny
Isaacs, Claudine
Janavicius, Ramunas
Lazaro, Conxi
Blanco, Ignacio
Ramus, Susan J.
Sucheston, Lara
Karlan, Beth Y.
Gross, Jenny
Ganz, Patricia A.
Beattie, Mary S.
Schmutzler, Rita K.
Wappenschmidt, Barbara
Meindl, Alfons
Arnold, Norbert
Niederacher, Dieter
Preisler-Adams, Sabine
Gadzicki, Dorotehea
Varon-Mateeva, Raymonda
Deissler, Helmut
Gehrig, Andrea
Sutter, Christian
Kast, Karin
Nevanlinna, Heli
Aittomaki, Kristiina
Simard, Jacques
Spurdle, Amanda B.
Beesley, Jonathan
Chen, Xiaoqing
Tomlinson, Gail E.
Weitzel, Jeffrey
Garber, Judy E.
Olopade, Olufunmilayo I.
Rubinstein, Wendy S.
Tung, Nadine
Blum, Joanne L.
Narod, Steven A.
Brummel, Sean
Gillen, Daniel L.
Lindor, Noralane
Fredericksen, Zachary
Pankratz, Vernon S.
Couch, Fergus J.
Radice, Paolo
Peterlongo, Paolo
Greene, Mark H.
Loud, Jennifer T.
Mai, Phuong L.
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Gerdes, Anne-Marie
Thomassen, Mads
Jensen, Uffe Birk
Skytte, Anne-Bine
Caligo, Maria A.
Lee, Andrew
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Neuhausen, Susan L.
CA SWE-BRCA
HEBON
EMBRACE
GEMO Study Collaborators
KConFab Investigators
OCGN
Consortium Investigators Modifiers
TI A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast
and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation
Carriers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID AMINO-ACID POLYMORPHISM; GROWTH-FACTOR-I; GENETIC-VARIATION; INSULIN;
RECEPTOR; EXPRESSION; IGF; NEOPLASIA; PROTEINS; FAMILY
AB Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.
Methods: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.
Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P-difference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).
Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.
Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(8); 1362-70. (C)2012 AACR.
C1 [McGuffog, Lesley; Lee, Andrew; Antoniou, Antonis C.] Univ Cambridge Worts Causeway, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Tischkowitz, Marc] Univ Cambridge, Dept Med Genet, Cambridge, England.
[Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Royal Brisbane Hosp, Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4029, Australia.
[Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Chaim Sheba Med Ctr, Oncogenet Unit, IL-52621 Tel Hashomer, Israel.
[Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel.
[Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon; Kaufman, Bella] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Liljegren, Annelie] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Lindblom, Annika] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[Olsson, Hakan] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden.
[Kristoffersson, Ulf] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden.
[Stenmark-Askmalm, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, Linkoping, Sweden.
[Melin, Beatrice] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain.
[Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain.
[Osorio, Ana; Benitez, Javier] Spanish Network Rare Dis CIBERER, Barcelona, Spain.
[Ramony Cajal, Teresa] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Spain.
[Lazaro, Conxi] Inst Catala Oncol, Lab Recerca Translac, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain.
[Blanco, Ignacio] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain.
[Stavropoulou, Alexandra V.] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece.
[Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany.
[Rookus, Matti; de Lange, Judith L.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England.
[Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England.
[Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England.
[Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England.
[Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland.
[Eccles, Diana] Univ Hosp Southampton NHS Fdn Trust, Wessex Clin Genet Serv, Southampton, Hants, England.
[Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England.
[Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England.
[Godwin, Andrew K.; Pathak, Harsh] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Stoppa-Lyonnet, Dominique; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine] Inst Curie, Dept Tumour Biol, Paris, France.
[Stoppa-Lyonnet, Dominique] Inst Curie, Unite INSERM U830, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France.
[Dreyfus, Helene] CHU Grenoble, Dept Genet, F-38043 Grenoble, France.
[Dreyfus, Helene] Univ Grenoble, Inst Albert Bonniot, Grenoble, France.
[Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure] Univ Lyon 1, CNRS, UMR5286, Ctr Rech Cancerol Lyon,INSERM,U1052, F-69365 Lyon, France.
[Sinilnikova, Olga M.; Leone, Melanie] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France.
[Collonge-Rame, Marie-Agnes] CHU Besancon, Serv Genet Biol Histol Biol Dev & Reprod, F-25030 Besancon, France.
[Sokolowska, Johanna] Nancy Univ, Ctr Hosp Reg & Univ, Med Genet Lab, Vandoeuvre Les Nancy, France.
[Hardouin, Agnes; Berthet, Pascaline] Ctr Francois Baclesse, F-14021 Caen, France.
[Buys, Saundra] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
[Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[Miron, Alex] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Brummel, Sean] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Terry, Mary Beth; Chung, Wendy] Columbia Univ, Dept Epidemiol, New York, NY USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[John, Esther M.] Stanford Canc Inst, Palo Alto, CA USA.
[Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[Singer, Christian F.; Tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese] Med Univ Vienna, Dept OB GYN, Vienna, Austria.
[Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
[Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark.
[Johannsson, Oskar T.] Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland.
[Johannsson, Oskar T.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Offit, Kenneth; Sarrel, Kara; Vijai, Joseph] Clin Canc Genet Lab, Buffalo, NY USA.
[Robson, Mark] Mem Sloan Kettering Canc Ctr, Buffalo, NY USA.
[Piedmonte, Marion R.] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA.
[Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Ding, Yuan C.; Weitzel, Jeffrey; Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France.
[Andrews, Lesley] Australia New Zealand Gynaecol Oncol Grp, Camperdown, NSW, Australia.
[Cohn, David] Ohio State Univ, Columbus Canc Council, Columbus, OH 43210 USA.
[Toland, Amanda Ewart] Ohio State Univ, Dept Internal Med, OSU Comprehens Canc Ctr, Div Human Canc Genet, Columbus, OH 43210 USA.
[Toland, Amanda Ewart] Ohio State Univ, OSU Comprehens Canc Ctr, Dept Mol Virol Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA.
[DeMars, Leslie R.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[DiSilvestro, Paul] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Rodriguez, Gustavo] NorthShore Univ Hlth Syst, Evanston, IL USA.
[Montagna, Marco; Agata, Simona] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy.
[Imyanitov, Evgeny] NN Petrov Oncol Res Inst, St Petersburg, Russia.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Janavicius, Ramunas] Vilnius Univ Hosp, Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania.
[Ramus, Susan J.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Karlan, Beth Y.; Gross, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CIO, Cologne, Germany.
[Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, D-40225 Dusseldorf, Germany.
[Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany.
[Gadzicki, Dorotehea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany.
[Varon-Mateeva, Raymonda] Charite, Campus Virchov Klinikum, Inst Human Genet, Berlin, Germany.
[Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Dept Med Genet, Ctr Familial Breast & Ovarian Canc, D-8700 Wurzburg, Germany.
[Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, Heidelberg, Germany.
[Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany.
[Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Nevanlinna, Heli] Univ Helsinki, Dept Clin Genet, Helsinki, Finland.
Univ Helsinki, Cent Hosp, Helsinki, Finland.
[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.
[KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia.
[Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Div Pediat Hematol Oncol, San Antonio, TX 78229 USA.
[Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Olopade, Olufunmilayo I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA.
[Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA.
[Narod, Steven A.] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada.
[OCGN] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Gillen, Daniel L.] Univ Calif Irvine, Dept Stat, Irvine, CA USA.
[Gillen, Daniel L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Lindor, Noralane] Mayo Clin, Dept Med Genet, Rochester, MN USA.
[Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Expt Oncol & Mol Med, Unit Genet Susceptibil Canc, Milan, Italy.
[Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Jensen, Uffe Birk] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark.
[Skytte, Anne-Bine] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy.
[Caligo, Maria A.] Univ Hosp Pisa, Pisa, Italy.
[Oosterwijk, Jan C.] Univ Groningen, Univ Med Ctr, Dept Genet, Groningen, Netherlands.
[van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, Dept Clin Genet, Maastricht, Netherlands.
[Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, GROW, Maastricht, Netherlands.
[Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Hereditary Canc Clin, NL-6525 ED Nijmegen, Netherlands.
[Jager, Agnes] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[van der Luijt, Rob B.; HEBON] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
RP Neuhausen, SL (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM sneuhausen@coh.org
RI Arnold, Norbert/E-3012-2010; Gronwald, Jacek/A-4576-2017; montagna,
marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Toland,
Amanda/E-4202-2011; Joseph, Vijai/J-9158-2013; Hoogerbrugge,
Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco,
Ignacio/D-2565-2013; Oosterwijk, Jan C./G-5770-2011; Osorio,
Ana/I-4324-2014; Jakubowska, Anna/O-8050-2014; Spurdle,
Amanda/A-4978-2011;
OI Arnold, Norbert/0000-0003-4523-8808; Gronwald,
Jacek/0000-0002-3643-2871; Janavicius, Ramunas/0000-0002-3773-8485;
montagna, marco/0000-0002-4929-2150; Joseph, Vijai/0000-0002-7933-151X;
Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984;
Robson, Mark/0000-0002-3109-1692; Eeles, Rosalind/0000-0002-3698-6241;
Nathanson, Katherine/0000-0002-6740-0901; Ramus,
Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897;
Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784
FU NIH [R01CA74415, P30CA033752]; Israel cancer association; Mutua
Madrilena Foundation; Red de Investigacion en Cancer [RD06/0020/1160];
Spanish Ministry of Science and Innovation [FIS P1081120,
SAF2010-20493]; Cancer Research UK [C1287/A10118, C1287/A11990,
C5047/A8385]; NIHR; NEYE Foundation; Clinical Genetics Branch, DCEG
National Cancer Institute (NCI); Community Oncology and Prevention
Trials Program-COPTRG National Cancer Institute (NCI); Russian
Foundation for Basic Research [10-04-92110, 10-04-92601, 11-04-00227];
Federal Agency for Science and Innovations [02.740.11.0780]; Royal
Society [JP090615]; Research Council of Lithuania [LIG-19/2010];
Institut Catala d'Oncologia (ICO); Asociacion Espanola Contra el Cancer,
Spanish Health Research Fund; Carlos III Health Institute; Catalan
Health Institute; Autonomous Government of Catalonia [ISCIIIRETIC
RD06/0020/1051, PI10/01422, PI10/31488, 2009SGR290]; American Cancer
Society [120950-SIOP-06-258-06-COUN]; German Cancer Aid [DKH 109076];
Helsinki University Central Hospital; Academy of Finland [132473];
Finnish Cancer Society; Sigrid Juselius Foundation; Canadian Institutes
of Health Research; Canadian Breast Cancer Research Alliance [019511];
NCI, under RFA [CA-06-503]; Cancer Care Ontario [U01 CA69467]; Cancer
Prevention Institute of California [U01 CA69417]; Columbia University
[U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer
Institute [U01 CA69446]; University of Melbourne [U01 CA69638]; National
Health and Medical Research Council of Australia; New South Wales Cancer
Council; Victorian Health Promotion Foundation (Australia); Victorian
Breast Cancer Research Consortium; NITA [P01 CA16094, R01 CA22435];
National Institutes of Health [P30 CA13696, P30 ES009089, UL1 RR025764,
R01278978]; National Center for Research Resources; National Center for
Advancing Translational Sciences; NCI [P30 CA042014]; NHMRC [145684,
288704, 454508]; US NCI at the NIH [NO2-CP-11019-50, N02-CP-65504];
Westat, Inc.; Breast cancer Research Foundation; Komen Foundation for
the Cure; Dutch Cancer Society [NKI1998-1854, NKI2004-3088,
NKI2007-3756]; ZonMW [91109024]; OSU Comprehensive Cancer Center;
[R01-CA083855]; [R01-CA102776]; [R01CA140323]; [U01CA69631];
[5U01CA113916]
FX Beckman Research Institute of the City of Hope (BRICOH) study was
supported by NIH R01CA74415 (S.L. Neuhausen) and P30CA033752. S.L.
Neuhausen is the Morris and Horowitz Families Endowed Professor. Sheba
Medical Center Study (SMC) was in part sponsored by a grant from the
Israel cancer association to E. Friedman on behalf of the Israeli
consortium of inherited breast cancer. University of Pennsylvania
(UPENN) study was supported by R01-CA083855 and R01-CA102776 (T. R.
Rebbeck). Spanish National Cancer Center (CNIO) study has been partially
funded by Mutua Madrilena Foundation, "Red de Investigacion en Cancer
RD06/0020/1160", and Spanish Ministry of Science and Innovation (FIS
P1081120 and SAF2010-20493). Epidemiologic study of BRCA1 and BRCA2
mutation carriers (EMBRACE) is supported by Cancer Research UK Grants
C1287/A10118 and C1287/A11990. D.G. Evans and F. Lalloo are supported by
an NIHR grant to the Biomedical Research Centre (Manchester, UK). The
Investigators at The Institute of Cancer Research and The Royal Marsden
NMS Foundation Trust are supported by an NIHR grant to the Biomedical
Research Centre at The Institute of Cancer Research and The Royal
Marsden NHS Foundation Trust. R. Eeles and E. B. Gomez Garcia are
supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer
Center (FCCC) study was supported by R01CA140323, U01CA69631, and
5U01CA113916 (to A.K. Godwin). Copenhagen Breast Cancer Study (CBCS) was
supported by the NEYE Foundation. Gynecologic Oncology Group (COG) was
supported through funding provided by both intramural (Clinical Genetics
Branch, DCEG) and extramural (Community Oncology and Prevention Trials
Program-COPTRG) National Cancer Institute (NCI) programs, and was based
in GOG's Cancer Prevention and Control Committee. N.N. Petrov Institute
of Oncology (NNPIO) study is supported by the Russian Foundation for
Basic Research (grants 10-04-92110, 10-04-92601, and 11-04-00227), the
Federal Agency for Science and Innovations (contract 02.740.11.0780),
and through a Royal Society International Joint Grant (JP090615). The
Baltic Familial Breast and Ovarian Cancer Consortium (BFBOCC, Latvia and
Lithuania) study is supported by the Research Council of Lithuania grant
LIG-19/2010 to R.J. Institut Catala d'Oncologia (ICO); Asociacion
Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III
Health Institute; Catalan Health Institute, and Autonomous Government of
Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051,
PI10/01422, PI10/31488, and 2009SGR290. UK and Gilds Radner Familial
Ovarian Cancer Registries (UKGRFOCR) study was supported by a project
grant from CRUK (to P. Peterlongo). Women's Cancer Program at the Samuel
Oschin Comprehensive Cancer Institute (WCP) is supported by American
Cancer Society (120950-SIOP-06-258-06-COUN). The German Consortium of
Hereditary Breast and Ovarian Cancer (GC-HBOC) was supported by a grant
of the German Cancer Aid (DKH 109076). Helsinki Breast Cancer Study
(HEBCS) was supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland (132473), the Finnish Cancer Society,
and the Sigrid Juselius Foundation. Interdisciplinary Health Research
International Team Breast Cancer Susceptibility (INHERIT BRCAs) 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.; The Breast Cancer Family
Registry (BCFR) was supported by the NCI, under RFA # CA-06-503, and
through cooperative agreements with members of the BCFR and principal
investigators, including Cancer Care Ontario (U01 CA69467), Cancer
Prevention Institute of California (U01 CA69417), Columbia University
(U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer
Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The
Australian BCFR was also supported by the National Health and Medical
Research Council of Australia, the New South Wales Cancer Council, the
Victorian Health Promotion Foundation (Australia), and the Victorian
Breast Cancer Research Consortium. M.C. Southey is an NHMRC Senior
Research Fellow and a Victorian Breast Cancer Research Consortium Group
Leader. J.L. Hopper is an Australia Fellow of the NHMRC and a Victorian
Breast Cancer Research Consortium Group Leader. Carriers at FCCC were
also identified with support from the NITA grants P01 CA16094 and R01
CA22435. The New York BCFR was also supported by National Institutes of
Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also
supported by the National Center for Research Resources and the National
Center for Advancing Translational Sciences, NIH Grant UL1 RR025764, and
by Award Number P30 CA042014 from the NCI. Kathleen Cuningham Consortium
for Research into Familial Breast Cancer (KCONFAB) is funded by NHMRC
grants 145684, 288704, and 454508. A.B. Spurdle is supported by an NHMRC
Senior Research Fellowship, and G-CT by an NHMRC Senior Principal
Research Fellowship. National Cancer Institute (NCI): P.L. Mai, J.T.
Loud, and M.H. Greene were funded by the Intramural Research Program of
the US NCI at the NIH with infrastructure support from contracts
NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. Mayo Clinic Study
(MAYO) was supported by NIH R01278978 and grants from the Breast cancer
Research Foundation and the Komen Foundation for the Cure. The
Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
study is supported by the Dutch Cancer Society grants NKI1998-1854,
NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. OSU CCG: This
work was funded by the OSU Comprehensive Cancer Center.
NR 31
TC 9
Z9 9
U1 2
U2 14
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 AUG
PY 2012
VL 21
IS 8
BP 1362
EP 1370
DI 10.1158/1055-9965.EPI-12-0229
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 987RC
UT WOS:000307433800016
PM 22729394
ER
PT J
AU Nichols, HB
Sprague, BL
Buist, DSM
Erwin, DO
Leach, CR
Patrick, H
AF Nichols, Hazel B.
Sprague, Brian L.
Buist, Diana S. M.
Erwin, Deborah O.
Leach, Corinne R.
Patrick, Heather
TI Careers in Cancer Prevention: What You May Not See from Inside Your
Academic Department-A Report from the American Society of Preventive
Oncology's Junior Members Interest Group
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
C1 [Nichols, Hazel B.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Sprague, Brian L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA.
[Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA.
[Erwin, Deborah O.] Roswell Pk Canc Inst, Off Canc Hlth Dispar Res, Buffalo, NY 14263 USA.
[Leach, Corinne R.] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA.
[Patrick, Heather] NCI, Behav Res Program, Rockville, MD USA.
RP Nichols, HB (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM nicholshb@niehs.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 2
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 AUG
PY 2012
VL 21
IS 8
BP 1393
EP 1395
DI 10.1158/1055-9965.EPI-12-0664
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 987RC
UT WOS:000307433800024
PM 22695736
ER
PT J
AU Ball, ER
Matsuda, MM
Dye, L
Hoffmann, V
Zerfas, PM
Szarek, E
Rich, A
Chitnis, AB
Stratakis, CA
AF Ball, Evan R.
Matsuda, Miho M.
Dye, Louis
Hoffmann, Victoria
Zerfas, Patricia M.
Szarek, Eva
Rich, Adam
Chitnis, Ajay B.
Stratakis, Constantine A.
TI Ultra-structural identification of interstitial cells of Cajal in the
zebrafish Danio rerio
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE Interstitial cell of Cajal (ICC); C-kit; Gastrointestinal motility;
Ultrastructure; Zebrafish; Danio rerio (Teleostei)
ID GASTROINTESTINAL STROMAL TUMORS; RECEPTOR TYROSINE KINASE; MURINE
SMALL-INTESTINE; SMOOTH-MUSCLE; KIT-LIGAND; C-KIT; TRACT; ICC;
ULTRASTRUCTURE; MORPHOGENESIS
AB The interstitial cells of Cajal (ICCs) are important mediators of gastrointestinal (GI) motility because of their role as pacemakers in the GI tract. In addition to their function, ICCs are also structurally distinct cells most easily identified by their ultra-structural features and expression of the tyrosine kinase receptor c-KIT. ICCs have been described in mammals, rodents, birds, reptiles, and amphibians, but there are no reports at the ultra-structural level of ICCs within the GI tract of an organism from the teleost lineage. We describe the presence of cells in the muscularis of the zebrafish intestine; these cells have similar features to ICCs in other vertebrates. The ICC-like cells are associated with the muscularis, are more electron-dense than surrounding smooth muscle cells, possess long cytoplasmic processes and mitochondria, and are situated opposing enteric nervous structures. In addition, immunofluorescent and immunoelectron-microscopic studies with antibodies targeting the zebrafish ortholog of a putative ICC marker, c-KIT (kita), showed c-kit immunoreactivity in zebrafish ICCs. Taken together, these data represent the first ultra-structural characterization of cells in the muscularis of the zebrafish Danio rerio and suggest that ICC differentiation in vertebrate evolution dates back to the teleost lineage.
C1 [Ball, Evan R.; Szarek, Eva; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bethesda, MD 20892 USA.
[Matsuda, Miho M.] NICHD, Mol Genet Lab, Sect Neural Dev Dynam, NIH, Bethesda, MD 20892 USA.
[Dye, Louis] NICHHD NICHD, Bethesda, MD 20892 USA.
[Hoffmann, Victoria; Zerfas, Patricia M.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA.
[Rich, Adam] SUNY Coll Brockport, Dept Biol Sci, Brockport, NY 14420 USA.
[Chitnis, Ajay B.] NICHD, Program Differentiat, Sect Neural Dev Dynam, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU National Institutes of Health [NIH DK071588-02]; NICHD, NIH
FX Portions of this work were generously funded by the National Institutes
of Health including NIH DK071588-02; the remaining of this work was
funded by the Intramural Program of NICHD, NIH.
NR 30
TC 7
Z9 8
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD AUG
PY 2012
VL 349
IS 2
BP 483
EP 491
DI 10.1007/s00441-012-1434-4
PG 9
WC Cell Biology
SC Cell Biology
GA 987FC
UT WOS:000307401200007
PM 22628160
ER
PT J
AU Seitz, AE
Olivier, KN
Adjemian, J
Holland, SM
Prevots, DR
AF Seitz, Amy E.
Olivier, Kenneth N.
Adjemian, Jennifer
Holland, Steven M.
Prevots, D. Rebecca
TI Trends in Bronchiectasis Among Medicare Beneficiaries in the United
States, 2000 to 2007
SO CHEST
LA English
DT Article
ID BEAM COMPUTED-TOMOGRAPHY; IDIOPATHIC BRONCHIECTASIS; ORPHAN DISEASE;
ACCURACY
AB Background: Bronchiectasis is a potentially serious condition characterized by permanent and abnormal widening of the airways, the prevalence of which is not well described. We sought to describe the trends, associated conditions, and risk factors for bronchiectasis among adults aged >= 65 years.
Methods: A 5% sample of the Medicare outpatient claims database was analyzed for bronchicctasis trends among beneficiaries aged >= 65 years from 2000 to 2007. Bronchiectasis was identified using International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis codes for acquired bronchiectasis. Period prevalence was used to describe sex- and race/ethnicity-specific rates, and annual prevalence was used to describe trends and age-specific rates. We estimated trends using Poisson regression and odds of bronchiectasis using multivariate logistic regression.
Results: From 2000 to 2007, 22,296 people had at least one claim for bronchiectasis. The 8-year period prevalence of bronchiectasis was 1,106 cases per 100,000 people. Bronchiectasis increased by 8.7% per year. We identified an interaction between the number of thoracic CT scans and race/ethnicity; period prevalence varied by a greater degree by number of thoracic CT scans among Asians compared with whites or blacks. Among people with one CT scan, Asians had a 2.5- and 3.9-fold higher period prevalence compared with whites and blacks.
Conclusions: Bronchiectasis prevalence increased significantly from 2000 to 2007 in the Medicare outpatient setting and varied by age, sex, and race/ethnicity. This increase could be due to a true increase in the condition or an increased recognition of previously undiagnosed cases. CHEST 2012; 142(2):432-439
C1 [Seitz, Amy E.; Olivier, Kenneth N.; Adjemian, Jennifer; Prevots, D. Rebecca] NIAID, NIH, Epidemiol Unit, Bethesda, MD 20892 USA.
[Seitz, Amy E.; Olivier, Kenneth N.; Adjemian, Jennifer; Holland, Steven M.; Prevots, D. Rebecca] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Seitz, AE (reprint author), NIAID, NIH, Epidemiol Unit, 8 W Dr,MSC 2665, Bethesda, MD 20892 USA.
EM seitza@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 30
TC 67
Z9 73
U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD AUG
PY 2012
VL 142
IS 2
BP 432
EP 439
DI 10.1378/chest.11-2209
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 987LJ
UT WOS:000307418200026
PM 22302301
ER
PT J
AU Levine, PH
Portera, CC
Hoffman, HJ
Yang, SX
Takikita, M
Duong, QN
Hewitt, SM
Swain, SM
AF Levine, Paul H.
Portera, Chia C.
Hoffman, Heather J.
Yang, Sherry X.
Takikita, Mikiko
Duong, Quyen N.
Hewitt, Stephen M.
Swain, Sandra M.
TI Evaluation of Lymphangiogenic Factors, Vascular Endothelial Growth
Factor D and E-Cadherin in Distinguishing Inflammatory From Locally
Advanced Breast Cancer
SO CLINICAL BREAST CANCER
LA English
DT Article
DE Biomarkers; E-cadherin; Intralymphatic tumor emboli; Lymphovascular
density; VEGF-D
ID MICROVESSEL-DENSITY; TYROSINE KINASE; TUMOR-CELLS; EXPRESSION;
CARCINOMA; EPIDEMIOLOGY; ANGIOGENESIS; PROGNOSIS; SURVEILLANCE; C-ERBB-2
AB Inflammatory breast cancer (IBC) appears to have clinical manifestations and a biological behavior different from those of locally advanced breast cancer (LABC), which may be important in studies on pathogenesis and treatment. The laboratory characteristics of IBC identified in this study indicate that the current case definition of IBC is too restrictive.
Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer that on presentation resembles locally advanced breast cancer (LABC). This study identified molecular features of IBC and LABC to investigate pathogenesis. Materials and Methods: This study involved 100 IBC cases identified in a national IBC registry and 107 non-IBC LABC cases from the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (CBCTR). Vascular endothelial growth factor D (VEGF-D) and E-cadherin levels and lymphatic vessel density (LVD) measured by podoplanin staining were examined by immunohistochemistry on paraffin-embedded tumor specimens. Intralymphatic tumor emboli (ILTE) were assessed in IBC and non-IBC tumors. IBC cases diagnosed by clinicians but not meeting the case definitions of the American Joint Committee on Cancer (AJCC) or the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI)(designated atypical IBC) were compared with AJCC- and/or SEER-defined cases (designated classic IBC). Results: E-cadherin levels were significantly higher in classic IBC cases compared with non-IBC cases (P = .031), whereas compared with classic IBC, patients with non-IBC LABC had significantly higher LVD (P = .0017) and VEGF-D levels (P < .0001). ILTE was marginally greater in classic IBC than in non-IBC (P = .046). The profile of laboratory values in atypical IBC cases more closely resembled those fitting classic IBC than LABC. Conclusion: E-cadherin levels, LVD, VEGF-D expression, and to a lesser extent, ILTE differed between classic IBC and non-IBC LABC. The similarity of laboratory results between atypical IBC and classic IBC vs. LABC suggests the need for broadening both the AJCC and SEER case definitions for this disease.
C1 [Levine, Paul H.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC 20037 USA.
[Portera, Chia C.; Swain, Sandra M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Takikita, Mikiko; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA.
[Swain, Sandra M.] Medstar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA.
RP Levine, PH (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC 20037 USA.
EM phlevine@gwu.edu
OI Hewitt, Stephen/0000-0001-8283-1788; Swain, Sandra/0000-0002-1320-3830
FU Department of Defense; Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research; [BC009014]
FX This work was supported in part by Grant No. BC009014 with the
Department of Defense and the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 38
TC 4
Z9 4
U1 0
U2 3
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD AUG
PY 2012
VL 12
IS 4
BP 232
EP 239
DI 10.1016/j.clbc.2012.04.005
PG 8
WC Oncology
SC Oncology
GA 988XP
UT WOS:000307525100002
PM 22694825
ER
PT J
AU Simon, RM
AF Simon, Richard M.
TI How to Develop Treatments for Biologically Heterogeneous "Diseases"
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID ADAPTIVE SIGNATURE DESIGN; CLINICAL-TRIAL DESIGN
AB The standard paradigm for the design of phase III clinical trials is not suitable for evaluation of molecularly targeted treatments in biologically heterogeneous groups of patients. Here, we comment on alternative clinical trial designs and propose a prospective discovery/evaluation framework for using tumor genomics in the design of phase III trials. Clin Cancer Res; 18(15); 4001-3. (C)2012 AACR.
C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Simon, RM (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsimon@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 11
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2012
VL 18
IS 15
BP 4001
EP 4003
DI 10.1158/1078-0432.CCR-12-1586
PG 3
WC Oncology
SC Oncology
GA 988PS
UT WOS:000307503600001
PM 22679178
ER
PT J
AU Herman, SEM
Johnson, AJ
AF Herman, Sarah E. M.
Johnson, Amy J.
TI Molecular Pathways: Targeting Phosphoinositide 3-Kinase p110-Delta in
Chronic Lymphocytic Leukemia
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID B-CELL ANTIGEN; PHOSPHATIDYLINOSITOL 3-KINASE; PI3K ISOFORMS;
ACTIVATION; INHIBITOR; SURVIVAL; CAL-101; DELTA; DIFFERENTIATION;
INSIGHTS
AB The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110 delta isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells). In addition, the clinical advances from targeting p110 delta are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110 delta in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics. Clin Cancer Res; 18(15); 4013-8. (C)2012 AACR.
C1 [Johnson, Amy J.] Ohio State Univ, Coll Pharm, Div Hematol, Dept Internal Med, Columbus, OH 43210 USA.
[Herman, Sarah E. M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Amy J.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
RP Johnson, AJ (reprint author), Ohio State Univ, Coll Pharm, Div Hematol, Dept Internal Med, OSU CCC Bldg,Room 445C,410 W 12th Ave, Columbus, OH 43210 USA.
EM amy.johnson@osumc.edu
FU Leukemia and Lymphoma Society; National Cancer Institute [P50 CA140158,
PO1 CA95426, PO1 CA81534, 1K12 CA133250]; Harry Mangurian Foundation; D.
Warren Brown Foundation
FX This work was supported by The Leukemia and Lymphoma Society and the
National Cancer Institute (P50 CA140158, PO1 CA95426, PO1 CA81534, 1K12
CA133250). Mr. and Mrs. Michael Thomas, The Harry Mangurian Foundation,
and The D. Warren Brown Foundation also supported this work.
NR 40
TC 29
Z9 30
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 AUG 1
PY 2012
VL 18
IS 15
BP 4013
EP 4018
DI 10.1158/1078-0432.CCR-11-1402
PG 6
WC Oncology
SC Oncology
GA 988PS
UT WOS:000307503600003
PM 22711705
ER
PT J
AU Wentzensen, N
Schwartz, L
Zuna, RE
Smith, K
Mathews, C
Gold, MA
Allen, RA
Zhang, R
Dunn, ST
Walker, JL
Schiffman, M
AF Wentzensen, Nicolas
Schwartz, Lauren
Zuna, Rosemary E.
Smith, Katie
Mathews, Cara
Gold, Michael A.
Allen, R. Andy
Zhang, Roy
Dunn, S. Terence
Walker, Joan L.
Schiffman, Mark
TI Performance of p16/Ki-67 Immunostaining to Detect Cervical Cancer
Precursors in a Colposcopy Referral Population
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; NEOPLASIA; CYTOLOGY; WOMEN; RISK;
BIOMARKERS; COHORT; PREVENTION
AB Purpose: Cytology-based screening has limited sensitivity to detect prevalent cervical precancers. Human papilloma virus (HPV) DNA testing is highly sensitive and provides a high, long-term reassurance of low risk of cervical cancer. However, the specificity of HPV DNA testing is limited, requiring additional, more disease-specific markers for efficient screening approaches.
Experimental Design: Liquid-based cytology samples were collected from 625 women referred to colposcopy. A slide was stained using the CINtec plus cytology assay. Pap cytology and HPV genotyping were conducted from the same vial. Clinical performance characteristics were calculated for all women, stratified by age, and for women referred with a low-grade squamous intraepithelial lesion (LSIL) Pap.
Results: p16/Ki-67 positivity increased with histologic severity, from 26.8% in normal histology, 46.5% in CIN1, 82.8% in CIN2 to 92.8% in CIN3. Among women with CIN3, p16/Ki-67 positivity increased from 77.8% for women younger than 30 years without HPV16 to 100% for women 30 years and older with HPV16. The sensitivity and specificity to detect CIN3+ were 93.2% and 46.1%, respectively, and increased to 97.2% and 60.0% among women 30 years and older. In women with high-risk (HR)-HPV-positive atypical squamous cells of undetermined significance (ASC-US) and LSIL, sensitivity and specificity for detection of CIN3 were 90.6% and 48.6%, respectively.
Conclusions: p16/Ki-67 testing could reduce referral to colposcopy by almost half while detecting the most severe cases of CIN3. The high sensitivity of p16/Ki-67 with significantly improved specificity compared with HPV testing makes p16/Ki-67 a viable option for LSIL triage. Further studies are required to evaluate p16/Ki-67 as triage marker in HPV-based screening strategies. Clin Cancer Res; 18(15); 4154-62. (C)2012 AACR.
C1 [Wentzensen, Nicolas; Schwartz, Lauren; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Zuna, Rosemary E.; Smith, Katie; Mathews, Cara; Allen, R. Andy; Zhang, Roy; Dunn, S. Terence; Walker, Joan L.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Gold, Michael A.] Vanderbilt Univ, Nashville, TN USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA.
EM wentzenn@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute; Qiagen
CareHPV; Roche
FX M. Schiffman has Other Commercial Research Support from Qiagen CareHPV
and Roche free specimen testing. No potential conflicts of interest were
disclosed by the other authors.; The study was supported by the
Intramural Research Program of the National Cancer Institute.
NR 21
TC 72
Z9 79
U1 2
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 AUG 1
PY 2012
VL 18
IS 15
BP 4154
EP 4162
DI 10.1158/1078-0432.CCR-12-0270
PG 9
WC Oncology
SC Oncology
GA 988PS
UT WOS:000307503600017
PM 22675168
ER
PT J
AU Kirk, MA
Fiumefreddo, A
Reynard, P
Hakkinen, P
AF Kirk, Mark A.
Fiumefreddo, Andrea
Reynard, Patti
Hakkinen, Pertti
TI Enhancing first responder preparedness for hazardous chemical incidents:
Training that combines high fidelity medical simulation with clinical
decision-support tools
SO CLINICAL TOXICOLOGY
LA English
DT Meeting Abstract
DE Public health; Cyanide; Organophosphate
C1 [Kirk, Mark A.; Fiumefreddo, Andrea; Reynard, Patti] Univ Virginia, Med Simulat Ctr, Charlottesville, VA USA.
[Hakkinen, Pertti] Natl Lib Med, Off Clin Toxicol, Specialized Informat Serv, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1556-3650
J9 CLIN TOXICOL
JI Clin. Toxicol.
PD AUG
PY 2012
VL 50
IS 7
MA 115
BP 625
EP 625
PG 1
WC Toxicology
SC Toxicology
GA 985WB
UT WOS:000307300100123
ER
PT J
AU Virtanen, JO
Jacobson, S
AF Virtanen, Jussi Oskari
Jacobson, Steve
TI Viruses and Multiple Sclerosis
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Multiple sclerosis; human herpesvirus 6; Epstein-Barr virus
ID EPSTEIN-BARR-VIRUS; HUMAN-HERPESVIRUS 6; VARICELLA-ZOSTER-VIRUS; MYELIN
BASIC-PROTEIN; POLYMERASE-CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS;
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHRONIC-FATIGUE-SYNDROME;
SERUM HHV-6 DNA; CEREBROSPINAL-FLUID
AB Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents.
C1 [Virtanen, Jussi Oskari; Jacobson, Steve] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5C-103,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
RI Virtanen, Jussi Oskari/D-3253-2013
FU Intramural NIH HHS [Z01 NS002817-19, Z01 NS003040-01, Z01 NS002817-18]
NR 177
TC 31
Z9 32
U1 4
U2 16
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD AUG
PY 2012
VL 11
IS 5
BP 528
EP 544
PG 17
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 975NY
UT WOS:000306519200006
PM 22583435
ER
PT J
AU Wu, DK
Kelley, MW
AF Wu, Doris K.
Kelley, Matthew W.
TI Molecular Mechanisms of Inner Ear Development
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID HAIR CELL-DEVELOPMENT; SEMICIRCULAR CANAL FORMATION; OTIC PLACODE
INDUCTION; NEURAL-TUBE DEFECTS; VESTIBULAR SENSORY EPITHELIA; DEVELOPING
MAMMALIAN COCHLEA; RETINOIC-ACID; PLANAR POLARITY; HEARING-LOSS;
REGULATES DEVELOPMENT
AB The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms.
C1 [Wu, Doris K.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
EM wud@nidcd.nih.gov
NR 142
TC 31
Z9 31
U1 1
U2 15
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 AUG
PY 2012
VL 4
IS 8
AR a008409
DI 10.1101/cshperspect.a008409
PG 19
WC Cell Biology
SC Cell Biology
GA 995RR
UT WOS:000308030500009
PM 22855724
ER
PT J
AU Crea, F
Paolicchi, E
Marquez, VE
Danesi, R
AF Crea, Francesco
Paolicchi, Elisa
Marquez, Victor E.
Danesi, Romano
TI Polycomb genes and cancer: Time for clinical application?
SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
LA English
DT Review
DE Polycomb; Cancer stem cell; EZH2; BMI1; DZNeP
ID METASTATIC PROSTATE-CANCER; AGGRESSIVE BREAST-CANCER; TUMOR-CELL
PROLIFERATION; STEM-CELLS; INCREASED EXPRESSION; DNA METHYLATION; GROUP
PROTEINS; PHARMACOLOGICAL DISRUPTION; PANCREATIC-CANCER;
MYELOID-LEUKEMIA
AB Polycomb group genes (PcGs) are epigenetic effectors, essential for stem cell self-renewal and pluripotency. Two main Polycomb repressive complexes (PRC1, PRC2) mediate gene silencing through histone post-translational modifications.
PcGs have been the focus of investigation in cancer research. Many cancer types show an over-expression of PcGs, predicting poor prognosis, metastasis and chemoresistance. Genetic polymorphisms of EZH2 (a PRC2 component) are significantly associated to lung cancer risk. Recently, 3-Deazaneplanocin A (DZNeP) was identified as an efficient inhibitor of PRC2 activity. DZNeP impairs cancer stem cell self-renewal and tumorigenicity.
Despite the well-established role of PcGs in cancer stem cell biology, few studies dissected the clinical significance of these genes. In this paper, we explore PcGs as predictive and prognostic factors in oncology, with particular emphasis on what they can add to current biomarkers. We also propose a model for the rational development of DZNeP-based anticancer regimens and suggest the therapeutic applications of this drug. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Crea, Francesco; Paolicchi, Elisa; Danesi, Romano] Univ Pisa, Div Pharmacol, Dept Internal Med, I-56100 Pisa, Italy.
[Marquez, Victor E.] NCI, Chem Biol Lab, Frederick, MD 21701 USA.
RP Crea, F (reprint author), Univ Pisa, Div Pharmacol, Dept Internal Med, Via Roma 55, I-56100 Pisa, Italy.
EM fr.crea@gmail.com; eli.paolicchi@gmail.com
RI Crea, Francesco /I-8383-2015;
OI Crea, Francesco/0000-0002-4903-2973; Paolicchi,
Elisa/0000-0001-6101-7576
FU Associazione Italiana per la Ricerca sul Cancro
NR 94
TC 41
Z9 44
U1 2
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1040-8428
J9 CRIT REV ONCOL HEMAT
JI Crit. Rev. Oncol./Hematol.
PD AUG
PY 2012
VL 83
IS 2
BP 184
EP 193
DI 10.1016/j.critrevonc.2011.10.007
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA 988ZK
UT WOS:000307529800003
PM 22112692
ER
PT J
AU Putnick, DL
Bornstein, MH
Lansford, JE
Chang, L
Deater-Deckard, K
Di Giunta, L
Gurdal, S
Dodge, KA
Malone, PS
Oburu, PO
Pastorelli, C
Skinner, AT
Sorbring, E
Tapanya, S
Tirado, LMU
Zelli, A
Alampay, LP
Al-Hassan, SM
Bacchini, D
Bombi, AS
AF Putnick, Diane L.
Bornstein, Marc H.
Lansford, Jennifer E.
Chang, Lei
Deater-Deckard, Kirby
Di Giunta, Laura
Gurdal, Sevtap
Dodge, Kenneth A.
Malone, Patrick S.
Oburu, Paul O.
Pastorelli, Concetta
Skinner, Ann T.
Sorbring, Emma
Tapanya, Sombat
Uribe Tirado, Liliana Maria
Zelli, Arnaldo
Pena Alampay, Liane
Al-Hassan, Suha M.
Bacchini, Dario
Bombi, Anna Silvia
TI Agreement in Mother and Father Acceptance-Rejection, Warmth, and
Hostility/Rejection/Neglect of Children Across Nine Countries
SO CROSS-CULTURAL RESEARCH
LA English
DT Article
DE parenting; acceptance; rejection; culture
ID REMEMBERED PARENTAL ACCEPTANCE; INTIMATE PARTNER ACCEPTANCE;
PSYCHOLOGICAL ADJUSTMENT; MATERNAL ACCEPTANCE; REARING BEHAVIOR;
YOUNG-CHILDREN; UNITED-STATES; ATTRIBUTIONS; ATTITUDES; AMERICAN
AB The authors assessed whether mothers' and fathers' self-reports of acceptance-rejection, warmth, and hostility/rejection/neglect (HRN) of their preadolescent children differ cross-nationally and relative to the gender of the parent and child in 10 communities in 9 countries, including China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States (N = 998 families). Mothers and fathers in all countries reported a high degree of acceptance and warmth, and a low degree of HRN, but countries also varied. Mothers reported greater acceptance of children than fathers in China, Italy, Sweden, and the United States, and these effects were accounted for by greater self-reported warmth in mothers than in fathers in China, Italy, the Philippines, Sweden, and Thailand and less HRN in mothers than in fathers in Sweden. Fathers reported greater warmth than mothers in Kenya. Mother and father acceptance-rejection were moderately correlated. Relative levels of mother and father acceptance and rejection appear to be country specific.
C1 [Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA.
[Lansford, Jennifer E.] Duke Univ, Social Sci Res Inst, Durham, NC USA.
[Chang, Lei] Chinese Univ Hong Kong, Dept Educ Psychol, Hong Kong, Hong Kong, Peoples R China.
[Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
[Di Giunta, Laura] Univ Roma La Sapienza, Interuniv Ctr Res Genesis & Dev Prosocial & Antis, Rome, Italy.
[Gurdal, Sevtap; Sorbring, Emma] Univ West, Trollhattan, Sweden.
[Malone, Patrick S.] Univ S Carolina, Columbia, SC 29208 USA.
[Oburu, Paul O.] Maseno Univ, Maseno, Kenya.
[Tapanya, Sombat] Chiang Mai Univ, Dept Psychiat, Fac Med, Chiang Mai 50000, Thailand.
[Uribe Tirado, Liliana Maria] Univ San Buenaventura, Fac Psychol, Medellin, Colombia.
[Zelli, Arnaldo] Univ Rome Foro Italico, Rome, Italy.
[Pena Alampay, Liane] Ateneo Manila Univ, Quezon City, Philippines.
[Al-Hassan, Suha M.] Hashemite Univ, Queen Rania Fac Childhood, Zarqa, Jordan.
[Bacchini, Dario] Univ Naples 2, Dept Psychol, Naples, Italy.
[Lansford, Jennifer E.; Dodge, Kenneth A.; Skinner, Ann T.] Duke Univ, Ctr Child & Family Policy, Durham, NC USA.
[Pastorelli, Concetta] Univ Roma La Sapienza, Dept Psychol, Rome, Italy.
[Bombi, Anna Silvia] Univ Roma La Sapienza, Fac Med & Psychol, Rome, Italy.
RP Putnick, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM putnickd@mail.nih.gov
RI Eclevia, Marian/I-6486-2013; ZELLI, ARNALDO/N-2333-2015;
OI ZELLI, ARNALDO/0000-0003-4020-8159; Bacchini, Dario/0000-0001-6140-9377;
Putnick, Diane/0000-0002-6323-749X
FU FIC NIH HHS [R03 TW008141, R03 TW008141-01]; NICHD NIH HHS [R01
HD054805, R01 HD054805-01A1]; NIDA NIH HHS [K05 DA015226-01, K01
DA024116, K01 DA024116-01A1, K05 DA015226]
NR 93
TC 15
Z9 15
U1 2
U2 31
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1069-3971
J9 CROSS-CULT RES
JI Cross-Cult. Res.
PD AUG
PY 2012
VL 46
IS 3
BP 191
EP 223
DI 10.1177/1069397112440931
PG 33
WC Social Sciences, Interdisciplinary
SC Social Sciences - Other Topics
GA 987WJ
UT WOS:000307448300001
PM 23024576
ER
PT J
AU Illuzzi, JL
Wilson, DM
AF Illuzzi, J. L.
Wilson, D. M., III
TI Base Excision Repair: Contribution to Tumorigenesis and Target in
Anticancer Treatment Paradigms
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE AP or abasic endonuclease; DNA polymerase; flap endonuclease;
carcinogenesis; repair inhibitor
ID DNA-POLYMERASE-BETA; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE;
DEOXYRIBONUCLEIC ACID POLYMERASE; ENHANCES CELLULAR-SENSITIVITY; HUMAN
APURINIC ENDONUCLEASE; SITE-DIRECTED MUTAGENESIS; SMALL-MOLECULE
INHIBITOR; ANDROGEN RECEPTOR GENE; TERMINAL 8-KDA DOMAIN; FEN1 MUTANT
MICE
AB Cancer treatments often lose their effectiveness due to the development of multiple drug resistance. Thus, identification of key proteins involved in the tumorigenic process and the survival mechanism(s), coupled with the design of novel therapeutic compounds (such as small molecule inhibitors), are essential steps towards the establishment of improved anticancer treatment strategies. DNA repair pathways and their proteins have been exposed as potential targets for combinatorial anticancer therapies that involve DNA-interactive cytotoxins, such as alkylating agents, because of their central role in providing resistance against DNA damage. In addition, an understanding of the tumor-specific genetics and associated DNA repair capacity has allowed research scientists and clinicians to begin to devise more targeted treatment strategies based on the concept of synthetic lethality. In this review, the repair mechanisms, as well as the links to cancer progression and treatment, of three key proteins that function in the base excision repair pathway, i.e. APE1, POL beta, and FEN1, are discussed.
C1 [Illuzzi, J. L.; Wilson, D. M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging. We thank Drs. Peter Sykora and
Leslie Hoh for their constructive comments on the review.
NR 202
TC 16
Z9 17
U1 2
U2 21
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD AUG
PY 2012
VL 19
IS 23
BP 3922
EP 3936
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 993HQ
UT WOS:000307848800008
PM 22788768
ER
PT J
AU Loh, YP
Koshimizu, H
Cawley, NX
Tota, B
AF Loh, Y. P.
Koshimizu, H.
Cawley, N. X.
Tota, B.
TI Serpinins: Role in Granule Biogenesis, Inhibition of Cell Death and
Cardiac Function
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Chromogranin A; serpinin; pGlu-serpinin; granule biogenesis;
neuroprotection; myocardial contractility
ID CHROMOGRANIN-A; NATRIURETIC PEPTIDES; MYOCARDIAL PRODUCTION; RAT-HEART;
MECHANISM; PHOSPHORYLATION; HYPERTENSION; PROHORMONE; PATHWAY; OXIDE
AB Serpinins are a family of peptides derived from proteolytic cleavage of the penultimate and the last pair of basic residues at the C-terminus of Chromogranin A. Three forms of naturally occurring serpinin have been found in AtT-20 pituitary cells and rat heart. They are serpinin, pyrogutaminated (pGlu) - serpinin and a C-terminally extended form, serpinin-RRG. In addition pGlu-serpinin has been found in brain, primarily in neurites and nerve terminals and shown to have protective effects against oxidative stress on neurons and pituitary cells. Serpinin has also been demonstrated to regulate granule biogenesis in endocrine cells by up-regulating the protease inhibitor, protease nexin-1 transcription via a cAMP-PKA-sp1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation. More recently, pGlu-serpinin has been demonstrated to enhance both myocardial contractility (inotropy) and relaxation (lusitropy). In the Langendorff perfused rat heart, pGlu-serpinin showed a concentration-dependent positive inotropic effect exerted through a cAMP-PKA dependent pathway. In conclusion, the serpinin peptides have profound effects at many levels that affect the endocrine and nervous systems and cardiac function.
C1 [Loh, Y. P.; Koshimizu, H.; Cawley, N. X.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Neurobiol, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Tota, B.] Univ Calabria, Dept Cell Biol, I-87030 Arcavacata Di Rende, CS, Italy.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Neurobiol, Program Dev Neurosci, NIH, Bldg 49,Room 5A22, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institutes of
Health, Bethesda, MD, USA; University of Calabria (Cosenza), Italy
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD, USA (YPL, HK,
NXC). B. T. was supported by a grant from the University of Calabria
(Cosenza), Italy.
NR 39
TC 4
Z9 5
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD AUG
PY 2012
VL 19
IS 24
BP 4086
EP 4092
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 993HW
UT WOS:000307849500007
PM 22834799
ER
PT J
AU Anderson-Dockter, H
Clark, T
Iwamoto, S
Lu, M
Fiore, D
Falanga, JK
Falanga, V
AF Anderson-Dockter, Heidi
Clark, Todd
Iwamoto, Satori
Lu, Ming
Fiore, David
Falanga, Jane K.
Falanga, Vincent
TI Diagnostic Utility of Cytokeratin 17 Immunostaining in Morpheaform Basal
Cell Carcinoma and for Facilitating the Detection of Tumor Cells at the
Surgical Margins
SO DERMATOLOGIC SURGERY
LA English
DT Article
ID HAIR-FOLLICLE; KERATIN EXPRESSION; INTERMEDIATE-FILAMENTS; DESMOPLASTIC
TRICHOEPITHELIOMA; PACHYONYCHIA-CONGENITA; DIFFERENTIATION; SKIN;
TRICHOBLASTOMA; POLYPEPTIDES; MUTATIONS
AB Background The morpheaform subtype of basal cell carcinoma (BCC) often presents a diagnostic histological challenge, and its true margin may be difficult to determine with accuracy. This tumor may also be difficult to distinguish from other adnexal neoplasms having a benign clinical course. Previous work has shown that cytokeratin 17 (CK17 or K17) expression is high in BCC. Objective To confirm the expression of K17 across the subtypes of superficial, nodular and morpheaform BCC variants and to compare K17 expression in each of these subtypes of BCC with that in two other adnexal neoplasms. Methods Tissue specimens from each tumor category were randomly collected, immunolabeled, and scored for K17 expression according to intensity and extent of immunostaining. Results Our results indicate that K17 is a useful marker in the identification and outlining of BCC. Moreover, in morpheaform BCC, K17 immunostaining clearly detected individual tumor cells well away from the dermal tumor strands that otherwise seemed nonmalignant according to hematoxylin and eosin staining alone. In addition, the expression of K17 in morpheaform BCC is capable (100% of specimens; p < .001) of distinguishing this tumor from desmoplastic trichoepithelioma. Conclusion We propose that K17 immunostaining could improve the diagnostic and surgical management of these tumors.
C1 [Anderson-Dockter, Heidi; Clark, Todd; Iwamoto, Satori; Lu, Ming; Fiore, David; Falanga, Jane K.; Falanga, Vincent] Roger Williams Med Ctr, Dept Dermatol & Skin Canc, Providence, RI 02908 USA.
[Iwamoto, Satori; Lu, Ming; Fiore, David; Falanga, Jane K.; Falanga, Vincent] NIH, Ctr Biomed Res Excellence, Roger Williams Med Ctr, Providence, RI USA.
[Iwamoto, Satori; Falanga, Vincent] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA.
[Falanga, Vincent] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Falanga, Vincent] Boston Univ, Sch Med, Dept Acad & Clin Affairs, Boston, MA 02118 USA.
RP Falanga, V (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, 50 Maude St, Providence, RI 02908 USA.
EM vfalanga@bu.edu
FU National Institutes of Health (NIH): National Institute of Arthritis and
Musculoskeletal and Skin Diseases [R01 AR060342]; National Institutes of
Health (NIH): National Center for Research Resources/National Institute
of General Medical Sciences [P20RR018757, P20 GM103414]; National
Institutes of Health (NIH): NIH Centers of Biomedical Research
Excellence Administrative and Imaging Cores
FX This work was supported by National Institutes of Health (NIH) grants
(V. Falanga, Principle Investigator): National Institute of Arthritis
and Musculoskeletal and Skin Diseases R01 AR060342; National Center for
Research Resources/National Institute of General Medical Sciences
P20RR018757 and P20 GM103414; NIH Centers of Biomedical Research
Excellence Administrative and Imaging Cores.
NR 35
TC 5
Z9 5
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1076-0512
J9 DERMATOL SURG
JI Dermatol. Surg.
PD AUG
PY 2012
VL 38
IS 8
BP 1357
EP 1366
DI 10.1111/j.1524-4725.2012.02417.x
PG 10
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 983KX
UT WOS:000307119300015
PM 22691048
ER
PT J
AU Williams, JS
Clausen, AR
McElhinny, SAN
Watts, BE
Johansson, E
Kunkel, TA
AF Williams, Jessica S.
Clausen, Anders R.
McElhinny, Stephanie A. Nick
Watts, Brian E.
Johansson, Erik
Kunkel, Thomas A.
TI Proofreading of ribonucleotides inserted into DNA by yeast DNA
polymerase epsilon
SO DNA REPAIR
LA English
DT Article
DE DNA replication; DNA polymerase epsilon; Ribonucleotides; Exonuclease;
Proofreading
ID SACCHAROMYCES-CEREVISIAE; ACTIVE-SITE; AMINO-ACID; REPLICATION;
FIDELITY; DEOXYRIBONUCLEOTIDE; DISCRIMINATION; EXONUCLEASE; INSTABILITY;
ERRORS
AB We have investigated the ability of the 3' exonuclease activity of Saccharomyces cerevisiae DNA polymerase epsilon (Pol epsilon) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol epsilon proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201 Delta strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2-4-fold in pol2-4 rnh2 Delta strains that are also defective in Pol e proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an 'incorrect' sugar is less efficient than is proofreading of an incorrect base, Pol epsilon does proofread newly inserted rNMPs to enhance genome stability. Published by Elsevier B.V.
C1 [Williams, Jessica S.; Clausen, Anders R.; McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Williams, Jessica S.; Clausen, Anders R.; McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Johansson, Erik] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
RI Clausen, Anders R./I-7229-2012
FU Division of Intramural Research of the National Institutes of Health
(NIH) [Z01 ES065070]; National Institute of Environmental Health
Sciences (NIEHS); Swedish Research Council; Swedish Cancer Society;
Smartafonden; Basic Science-oriented Biotechnology, Medical Faculty of
Umea University
FX This work was supported by Project Z01 ES065070 to T.A.K. from the
Division of Intramural Research of the National Institutes of Health
(NIH), National Institute of Environmental Health Sciences (NIEHS), and
by the Swedish Research Council, the Swedish Cancer Society,
Smartafonden and the fund for Basic Science-oriented Biotechnology,
Medical Faculty of Umea University to E.J.
NR 34
TC 27
Z9 27
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 1
PY 2012
VL 11
IS 8
BP 649
EP 656
DI 10.1016/j.dnarep.2012.05.004
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 988ZN
UT WOS:000307530100002
PM 22682724
ER
PT J
AU Drake, JW
von Borstel, RW
Hennig, UGG
AF Drake, John W. (Jan)
von Borstel, Reid W.
Hennig, Ursula G. G.
TI In Memoriam R. C. (Jack) von Borstel (January 24, 1925-April 19, 2012)
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Editorial Material
ID ALPHA-PARTICLE BOMBARDMENT; SACCHAROMYCES-CEREVISIAE; HABROBRACON EGG;
YEAST
C1 [Drake, John W. (Jan)] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[von Borstel, Reid W.] Wellstat Therapeut Corp, Gaithersburg, MD USA.
[Hennig, Ursula G. G.] Univ Alberta, Dept Biol Sci, Fac Sci, Edmonton, AB, Canada.
RP Drake, JW (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 12
TC 0
Z9 0
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD AUG
PY 2012
VL 53
IS 7
BP 493
EP 494
DI 10.1002/em.21714
PG 2
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 986RQ
UT WOS:000307362500001
ER
PT J
AU de Mello, RAF
Nacif, MS
dos Santos, AASMD
Cury, RC
Rochitte, CE
Marchiori, E
AF Fernades de Mello, Ricardo Andrade
Nacif, Marcelo Souto
dos Santos, Alair Augusto Sarmet M. D.
Cury, Ricardo Caldeira
Rochitte, Carlos Eduardo
Marchiori, Edson
TI Diagnostic performance of combined cardiac MRI for detection of coronary
artery disease
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Magnetic resonance imaging; Coronary angiography; Coronary artery
disease
ID MAGNETIC-RESONANCE PERFUSION; LATE GADOLINIUM ENHANCEMENT; FRACTIONAL
FLOW RESERVE; EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL STRESS PERFUSION;
X-RAY ANGIOGRAPHY; 1ST-PASS PERFUSION; NONINVASIVE DETECTION;
RANDOMIZED-TRIAL; PROGNOSTIC VALUE
AB Objective: To evaluate the diagnostic performance of stress perfusion cardiac MR (CMR) for detecting significant CAD (>= 70% narrowing) in comparison with invasive coronary angiography (ICA) as a reference standard.
Methods: Examinations of 54 patients who underwent both stress perfusion CMR and ICA for investigation of CAD between 2007 and 2009 were evaluated. The CMR protocol included dipyridamole stress and rest perfusion, stress and rest cine MRI for assessment of ventricular function and delayed gadolinium enhancement for assessment of myocardial viability and detection of infarction. CMR interpretation was performed by 2 observers blinded to the results of ICA and the clinical history.
Results: From a total of 54 patients, 37 (68.5%) showed significant CAD in 71 coronary territories. A perfusion defect was detected in 35 patients and in 69 coronary territories. Individual stress perfusion CMR evaluation showed the highest accuracy (83%) of the CMR techniques. The combined analysis using all sequences increased the overall accuracy of CMR to 87%.
Conclusion: Combination of perfusion and cine-MR during stress/rest, associated to delayed enhancement in the same protocol improves CMRI diagnostic accuracy and sensitivity for patients with significant coronary stenosis, and may therefore be helpful for risk stratification and defining treatment strategies. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Fernades de Mello, Ricardo Andrade; Nacif, Marcelo Souto; dos Santos, Alair Augusto Sarmet M. D.] HCN, Niteroi, RJ, Brazil.
[Fernades de Mello, Ricardo Andrade; Nacif, Marcelo Souto; Marchiori, Edson] Univ Fed Rio de Janeiro, Dept Radiol, Rio de Janeiro, Brazil.
[Fernades de Mello, Ricardo Andrade] UFES, Vitroria, ES, Brazil.
[Nacif, Marcelo Souto] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Nacif, Marcelo Souto; dos Santos, Alair Augusto Sarmet M. D.; Marchiori, Edson] Univ Fed Fluminense, Dept Radiol, Niteroi, RJ, Brazil.
[Cury, Ricardo Caldeira] Baptist Cardiac & Vasc Inst, Miami, FL USA.
[Rochitte, Carlos Eduardo] HCFMUSP, Dept Cardiovasc MRI & CT InCor, Sao Paulo, SP, Brazil.
RP Nacif, MS (reprint author), 4853 Cordell Ave,Apt 419, Bethesda, MD 20814 USA.
EM ricardoafmello@gmail.com; msnacif@gmail.com; alairsarmet@globo.com;
RCury@baptisthealth.net; rochitte@incor.usp.br; edmarchiori@gmail.com
RI Marchiori, Edson/C-1205-2013
NR 53
TC 3
Z9 4
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0720-048X
J9 EUR J RADIOL
JI Eur. J. Radiol.
PD AUG
PY 2012
VL 81
IS 8
BP 1782
EP 1789
DI 10.1016/j.ejrad.2011.05.019
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 983NO
UT WOS:000307126200036
PM 21664778
ER
PT J
AU Zhou, HY
Chang, S
Rao, M
AF Zhou, Hongyan
Chang, Stephen
Rao, Mahendra
TI Human cord blood applications in cell therapy: looking back and look
ahead
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE clinical application; cord blood; GMP; regenerative medicine;
reprogramming; transplantation
ID PLURIPOTENT STEM-CELLS; BONE-MARROW; IPS CELLS; TRANSPLANTATION;
GENERATION; LEUKEMIA; BANKING; PATIENT; DIFFERENTIATION; FIBROBLASTS
AB Introduction: Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed.
Areas covered: UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed.
Expert opinion: Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.
C1 [Rao, Mahendra] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA.
[Zhou, Hongyan; Chang, Stephen] New York Stem Cell Fdn, New York, NY USA.
RP Rao, M (reprint author), NIH, Natl Ctr Regenerat Med, Bldg 10, Bethesda, MD 20892 USA.
EM raomah@mail.nih.gov
RI zhou, hongyan/B-3689-2011
OI zhou, hongyan/0000-0001-5919-7715
FU New York Stem Cell Foundation; NIH
FX Dr. H Zhou and Dr. S Chang have received support from New York Stem Cell
Foundation. Dr. M Rao and NIH CRM are supported as a common fund
initiative of the NIH. None of the other authors have competing
interests to declare. The authors would like to thank Dr. Caroline
Marshall from the New York Stem Cell Foundation for editorial
assistance.
NR 50
TC 6
Z9 6
U1 1
U2 8
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 AUG
PY 2012
VL 12
IS 8
BP 1059
EP 1066
DI 10.1517/14712598.2012.691161
PG 8
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 984QF
UT WOS:000307205400008
PM 22681655
ER
PT J
AU Ranguelova, K
Ganini, D
Bonini, MG
London, RE
Mason, RP
AF Ranguelova, Kalina
Ganini, Douglas
Bonini, Marcelo G.
London, Robert E.
Mason, Ronald P.
TI Kinetics of the oxidation of reduced Cu,Zn-superoxide dismutase by
peroxymonocarbonate
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Peroxymonocarbonate; Superoxide dismutase; Carbonate anion radical
ID ZINC SUPEROXIDE-DISMUTASE; CARBONATE-RADICAL-ANION;
AMYOTROPHIC-LATERAL-SCLEROSIS; ENHANCED PEROXIDASE-ACTIVITY;
HYDROGEN-PEROXIDE; NITROGEN-DIOXIDE; COPPER,ZINC-SUPEROXIDE DISMUTASE;
ALPHA-SYNUCLEIN; HUMAN COPPER; ACTIVE-SITE
AB Kinetic evidence is reported for the role of the peroxymonocarbonate, HOOCO2-, as an oxidant for reduced Cu,Zn-superoxide dismutase-Cu(I) (SOD1) during the peroxidase activity of the enzyme. The formation of this reactive oxygen species results from the equilibrium between hydrogen peroxide and bicarbonate. Recently, peroxymonocarbonate has been proposed to be a key substrate for reduced SOD1 and has been shown to oxidize SOD1-Cu(I) to SOD1-Cu(II) much faster than H2O2. We have reinvestigated the kinetics of the reaction between SOD1-Cu(I) and HOOCO2- by using conventional stopped-flow spectrophotometry and obtained a second-order rate constant of k = 1600 +/- 100 M-1 s(-1) for SOD1-Cu(I) oxidation by HOOCO2-. Our results demonstrate that peroxymonocarbonate oxidizes SOD1-Cu(I) to SOD1-Cu(II) and is in turn reduced to the carbonate anion radical. It is proposed that the dissociation of His61 from the active site Cu(I) in SOD-Cu(l) contributes to this chemistry by facilitating the binding of larger anions, such as peroxymonocarbonate. Published by Elsevier Inc.
C1 [Ranguelova, Kalina; Ganini, Douglas; Mason, Ronald P.] NIEHS, Lab Pharmacol & Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Med, Cardiol Sect, Chicago, IL USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Pharmacol, Chicago, IL USA.
[London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Toxicol, NIH, MD F0-02,POBox 12233, Res Triangle Pk, NC 27709 USA.
EM mason4@niehs.nih.gov
FU NIH, NIEHS
FX We acknowledge Mrs. Mary J. Mason and Dr. Ann Motten for their help in
the preparation of the manuscript. The authors also thank Dr. Richard S.
Magliozzo from Brooklyn College for the use of his stopped-flow
spectrophotometer. This work has been supported by the Intramural
Research Program of the NIH, NIEHS.
NR 48
TC 10
Z9 10
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 1
PY 2012
VL 53
IS 3
BP 589
EP 594
DI 10.1016/j.freeradbiomed.2012.04.029
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 986DP
UT WOS:000307321500020
PM 22569304
ER
PT J
AU Meissner, EG
Suffredini, AF
Kottilil, S
AF Meissner, Eric G.
Suffredini, Anthony F.
Kottilil, Shyamasundaran
TI Opportunities in proteomics to understand hepatitis C and HIV
coinfection
SO FUTURE VIROLOGY
LA English
DT Review
DE coinfection; fibrosis; hepatitis C; HIV; proteomics; treatment
prediction
ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION ANTIRETROVIRAL THERAPY;
LIVER-ENZYME ELEVATION; MASS-SPECTROMETRY; INFECTED PATIENTS;
QUANTITATIVE PROTEOMICS; FIBROSIS PROGRESSION; INCREASING BURDEN;
NATURAL-HISTORY; PLUS RIBAVIRIN
AB Antiretroviral therapy has significantly reduced morbidity and mortality associated with HIV infection. However, coinfection with HCV results in a more complicated disease course for both infections. HIV infection dramatically impacts the natural history of chronic liver disease due to HCV. Coinfected patients not on antiretroviral therapy for HIV develop liver fibrosis and cirrhosis at a faster rate, clear acute infection less commonly and respond to IFN-alpha-based therapy for chronic infection less often than HCV-monoinfected patients. The interaction between these two viruses, the immune system and the fibrotic machinery of the liver remains incompletely understood. In this review, we discuss recent advances in proteomics as applied to HCV and HIV and highlight issues in coinfection that are amenable to further discovery through proteomic approaches. We focus on clinical predictors of liver fibrosis and treatment outcome as these have the greatest potential clinical applicability.
C1 [Meissner, Eric G.; Kottilil, Shyamasundaran] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Suffredini, Anthony F.] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Meissner, EG (reprint author), NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
EM eric.meissner@nih.gov
FU NIH (National Institute of Allergy and Infectious Diseases); NIH (NIH
Clinical Center)
FX This project has been funded in whole or in part with federal funds from
the Intramural Research Program of the NIH (National Institute of
Allergy and Infectious Diseases and the NIH Clinical Center). The
authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 64
TC 0
Z9 0
U1 0
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0794
J9 FUTURE VIROL
JI Future Virol.
PD AUG
PY 2012
VL 7
IS 8
BP 759
EP 765
DI 10.2217/FVL.12.67
PG 7
WC Virology
SC Virology
GA 986DR
UT WOS:000307321700008
PM 23105947
ER
PT J
AU Hogart, A
Lichtenberg, J
Ajay, SS
Anderson, S
Margulies, EH
Bodine, DM
AF Hogart, Amber
Lichtenberg, Jens
Ajay, Subramanian S.
Anderson, Stacie
Margulies, Elliott H.
Bodine, David M.
CA NIH Intramural Sequencing Ctr
TI Genome-wide DNA methylation profiles in hematopoietic stem and
progenitor cells reveal overrepresentation of ETS transcription factor
binding sites
SO GENOME RESEARCH
LA English
DT Article
ID SELF-RENEWAL; ENDOGLIN EXPRESSION; DIFFERENTIATION; PROMOTER;
5-HYDROXYMETHYLCYTOSINE; METHYLTRANSFERASE; ENDOTHELIUM; COMMITMENT;
QUIESCENCE; METHYLOME
AB DNA methylation is an essential epigenetic mark that is required for normal development. Knockout of the DNA methyltransferase enzymes in the mouse hematopoietic compartment reveals that methylation is critical for hematopoietic differentiation. To better understand the role of DNA methylation in hematopoiesis, we characterized genome-wide DNA methylation in primary mouse hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), and erythroblasts (ERYs). Methyl binding domain protein 2 (MBD) enrichment of DNA followed by massively parallel sequencing (MBD-seq) was used to map genome-wide DNA methylation. Globally, DNA methylation was most abundant in HSCs, with a 40% reduction in CMPs, and a 67% reduction in ERYs. Only 3% of peaks arise during differentiation, demonstrating a genome-wide decline in DNA methylation during erythroid development. Analysis of genomic features revealed that 98% of promoter CpG islands are hypomethylated, while 20%-25% of non-promoter CpG islands are methylated. Proximal promoter sequences of expressed genes are hypomethylated in all cell types, while gene body methylation positively correlates with gene expression in HSCs and CMPs. Elevated genome-wide DNA methylation in HSCs and the positive association between methylation and gene expression demonstrates that DNA methylation is a mark of cellular plasticity in HSCs. Using de novo motif discovery, we identified overrepresented transcription factor consensus binding motifs in methylated sequences. Motifs for several ETS transcription factors, including GABPA and ELF1, are overrepresented in methylated regions. Our genome-wide survey demonstrates that DNA methylation is markedly altered during myeloid differentiation and identifies critical regions of the genome and transcription factor programs that contribute to hematopoiesis.
C1 [Hogart, Amber; Lichtenberg, Jens; Anderson, Stacie; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Ajay, Subramanian S.; Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Anderson, Stacie] NHGRI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
[NIH Intramural Sequencing Ctr] NHGRI, NIH Intramural Sequencing Ctr, NIH, Rockville, MD 20852 USA.
RP Bodine, DM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM tedyaz@mail.nih.gov
FU NHGRI; National Institute of General Medical Sciences Pharmacology
Research Associate Training Program
FX This work was funded from NHGRI intramural funds. A.H. is funded by the
National Institute of General Medical Sciences Pharmacology Research
Associate Training Program. We thank Dr. Ross Hardison for critical
evaluation of this manuscript. We also thank the NHGRI Embryonic Stem
Cell and Transgenic Mouse Core Facility for animal resources.
NR 48
TC 49
Z9 51
U1 0
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD AUG
PY 2012
VL 22
IS 8
BP 1407
EP 1418
DI 10.1101/gr.132878.111
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 983BD
UT WOS:000307090300003
PM 22684279
ER
PT J
AU Krumm, N
Sudmant, PH
Ko, A
O'Roak, BJ
Malig, M
Coe, BP
Quinlan, AR
Nickerson, DA
Eichler, EE
AF Krumm, Niklas
Sudmant, Peter H.
Ko, Arthur
O'Roak, Brian J.
Malig, Maika
Coe, Bradley P.
Quinlan, Aaron R.
Nickerson, Deborah A.
Eichler, Evan E.
CA NHLBI Exome Sequencing Project
TI Copy number variation detection and genotyping from exome sequence data
SO GENOME RESEARCH
LA English
DT Article
ID STRUCTURAL VARIATION; HUMAN GENOME; VARIANTS; AUTISM
AB While exome sequencing is readily amenable to single-nucleotide variant discovery, the sparse and nonuniform nature of the exome capture reaction has hindered exome-based detection and characterization of genic copy number variation. We developed a novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy number polymorphic (CNP) loci with high sensitivity and specificity from exome sequencing data. We estimate the precision of our algorithm using 122 trios (366 exomes) and show that this method can be used to reliably predict (94% overall precision) both de novo and inherited rare CNVs involving three or more consecutive exons. We demonstrate that exome-based genotyping of CNPs strongly correlates with whole-genome data (median r(2) = 0.91), especially for loci with fewer than eight copies, and can estimate the absolute copy number of multi-allelic genes with high accuracy (78% call level). The resulting user-friendly computational pipeline, CoNIFER (copy number inference from exome reads), can reliably be used to discover disruptive genic CNVs missed by standard approaches and should have broad application in human genetic studies of disease.
C1 [Krumm, Niklas; Sudmant, Peter H.; Ko, Arthur; O'Roak, Brian J.; Malig, Maika; Coe, Bradley P.; Nickerson, Deborah A.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
[NHLBI Exome Sequencing Project] NHLBI, NHLBI Exome Sequencing Project, NIH, Bethesda, MD 20892 USA.
[Quinlan, Aaron R.] Univ Virginia, Ctr Publ Hlth Gen, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
RI Coe, Bradley/A-2878-2009;
OI Sudmant, Peter/0000-0002-9573-8248; Quinlan, Aaron/0000-0003-1756-0859;
O'Roak, Brian/0000-0002-4141-0095
FU NIH [HD065285, HHSN273200800010C, HL102926]; Simons Foundation Autism
Research Initiative
FX We thank S. Ng, S. McGee, and T. Brown for helpful comments in the
preparation of this manuscript; M. State and the Simons Simplex
Collection Genetics Consortium for providing Illumina genotyping data;
K. Patterson for exome coverage statistics; and A. Schachtel for
suggesting the CoNIFER name. This work was supported by NIH grants
HD065285 (E.E.E.), HHSN273200800010C (D.A.N.), and HL102926 (D.A.N.) and
the Simons Foundation Autism Research Initiative (E.E.E.). E.E.E. is an
investigator of the Howard Hughes Medical Institute.
NR 22
TC 164
Z9 166
U1 0
U2 22
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD AUG
PY 2012
VL 22
IS 8
BP 1525
EP 1532
DI 10.1101/gr.138115.112
PG 8
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 983BD
UT WOS:000307090300014
PM 22585873
ER
PT J
AU Amodio, E
Cusi, MG
Valenti, RM
Valentini, M
Mammina, C
Gori-Savellini, G
Vitale, F
Romano, N
Goedert, JJ
Calamusa, G
AF Amodio, Emanuele
Cusi, Maria Grazia
Valenti, Rosalia Maria
Valentini, Melissa
Mammina, Caterina
Gori-Savellini, Gianni
Vitale, Francesco
Romano, Nino
Goedert, James J.
Calamusa, Giuseppe
TI Immunoglobulin M seropositivity for Toscana virus in a random population
sample in Sicily
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Toscana virus; IgM seropositivity; Sicily
ID PHLEBOTOMUS-PERNICIOSUS; BLOOD-DONORS; PHLEBOVIRUS; PREVALENCE;
SEROPREVALENCE; EXPOSURE; VECTOR; FRANCE; FLIES; AREA
AB Objectives: High Toscana virus (TOSV) antibody seropositivity rates have been documented in the last decade, especially in the Mediterranean area. It is unclear if these rates are associated with a recent or past exposure to the virus. This is of importance, as primary infection can cause neurologic complications, especially in adults. The aim of the present study was to assess the current active TOSV circulation in western Sicily.
Methods: A cross-sectional seroprevalence study was conducted on 271 individuals aged 4-92 years, sampled from the general population of a small city. Each participant completed a self-administered questionnaire and provided serum, which was analyzed for the presence of specific anti-TOSV IgM and IgG.
Results: Anti-TOSV IgM was detected in eight (3.0%) participants, of whom only three had anti-TOSV IgG. The prevalence of anti-TOSV IgM was highest in subjects aged 25-34 and 35-44 years (7.1% and 4.8%, respectively). All subjects positive for anti-TOSV IgM were resident in the suburban area.
Conclusions: The detection of IgM documented the circulation of TOSV, a Phlebovirus, in a random population sample of Sicilian adults. The highest risk of TOSV seroconversion in subjects living in the suburbs appears to suggest a high density of TOSV vectors in peri-urban areas. (C) 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
C1 [Amodio, Emanuele; Valenti, Rosalia Maria; Mammina, Caterina; Vitale, Francesco; Romano, Nino; Calamusa, Giuseppe] Univ Palermo, Dept Sci Hlth Promot G DAlessandro, I-90127 Palermo, Italy.
[Cusi, Maria Grazia; Valentini, Melissa; Gori-Savellini, Gianni] Univ Siena, Microbiol Sect, Dept Mol Biol, I-53100 Siena, Italy.
[Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Amodio, E (reprint author), Univ Palermo, Dept Sci Hlth Promot G DAlessandro, Via Vespro 133, I-90127 Palermo, Italy.
EM emanuele.amodio@unipa.it
RI Mammina, Caterina/M-9339-2013;
OI Gori Savellini, Gianni/0000-0003-2287-9258; Mammina,
Caterina/0000-0003-2881-8018
FU Fondazione Carlo Denegri Onlus
FX The authors are grateful to the Fondazione Carlo Denegri Onlus for
partially funding this study. Thanks are also due to the local Municipal
Administration of Calatafimi-Segesta (Trapani), Filippo Cangemi, Maria
Adelaide D'Anna, Salvatore Gerbino, Vincenzo Malerba, Claudio Minore,
Patrizia Parisi, Giovanni Vaiana, Leonardo Vanella, and Felicia Coraci
for their helpful contribution to the study, and especially to the study
participants.
NR 24
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD AUG
PY 2012
VL 16
IS 8
BP E633
EP E635
DI 10.1016/j.ijid.2012.04.012
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 983MT
UT WOS:000307124100010
PM 22726418
ER
PT J
AU Campos, CR
Schroter, C
Wang, XQ
Miller, DS
AF Campos, Christopher R.
Schroeter, Christian
Wang, Xueqian
Miller, David S.
TI ABC transporter function and regulation at the blood-spinal cord barrier
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE capillaries; confocal imaging; Dioxin; membrane transport;
P-glycoprotein
ID XENOBIOTIC EFFLUX TRANSPORTERS; AMYOTROPHIC-LATERAL-SCLEROSIS; MEDIATED
UP-REGULATION; BRAIN-BARRIER; P-GLYCOPROTEIN; ENDOTHELIAL-CELLS;
DISORDERS; RATS; CAR; CNS
AB We present here an initial characterization of ATP binding cassette (ABC) transporter function and regulation at the blood-spinal cord barrier. We isolated capillaries from rat spinal cords and studied transport function using a confocal microscopy-based assay and protein expression using western blots. These capillaries exhibited transport function and protein expression of P-glycoprotein (Abcb1), multidrug resistance protein 2 (Mrp2, Abcc2), and breast cancer-related protein (Bcrp, Abcg2). Exposing isolated capillaries to dioxin (activates aryl hydrocarbon receptor) increased transport mediated by all three transporters. Brain and spinal cord capillaries from dioxin-dosed rats exhibited increased P-glycoprotein-mediated transport and increased protein expression for all three ABC transporters. These findings indicate similar ABC transporter expression, function, and regulation at the blood-spinal cord and blood-brain barriers. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1559-1566; doi: 10.1038/jcbfm.2012.47; published online 4 April 2012
C1 [Campos, Christopher R.; Schroeter, Christian; Wang, Xueqian; Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Schroeter, Christian] Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany.
RP Miller, DS (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM miller@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health.
NR 21
TC 14
Z9 14
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
IS 8
BP 1559
EP 1566
DI 10.1038/jcbfm.2012.47
PG 8
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983DT
UT WOS:000307099400012
PM 22472606
ER
PT J
AU Bower, S
Suomi, SJ
Paukner, A
AF Bower, Seth
Suomi, Stephen J.
Paukner, Annika
TI Evidence for Kinship Information Contained in the Rhesus Macaque (Macaca
mulatta) Face
SO JOURNAL OF COMPARATIVE PSYCHOLOGY
LA English
DT Article
DE kin recognition; facial similarity; rhesus macaque; principal component
analysis
ID VISUAL KIN RECOGNITION; SOCIAL RELATIONSHIPS; PAPIO-CYNOCEPHALUS;
MONKEYS; DISCRIMINATION; RELATEDNESS; FAMILIARITY; PREFERENCES;
CHIMPANZEES; NEMESTRINA
AB The ability to recognize kin is an important social skill for primates. Humans are adept at using facial similarity to recognize likely kin, and there is evidence that nonhuman primates are also able to use facial similarity to make judgments about kinship. However, if and how nonhuman primate faces actually contain kinship information remains unclear. To test whether there is objectively measurable facial similarity in related nonhuman primates, we compared facial measurements from related (paternal half-sisters) and unrelated adult female rhesus macaques (Macaca mulatta). Facial measurements were first summarized into 5 factors using a principal component analysis. Differences in these factors between the faces of related macaques were compared with differences between the faces of random unrelated macaques and of age-matched unrelated macaques. The difference in facial measurements between related macaques was significantly smaller than the difference in facial measurements of either group of unrelated macaques, constituting an objective measure of facial similarity in macaque kin. These results indicate that kinship information is contained in the rhesus macaque face and suggest that nonhuman primates may rely in part on facial similarity to distinguish kin.
C1 [Bower, Seth; Suomi, Stephen J.; Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20873 USA.
RP Bower, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Anim Ctr, POB 529, Poolesville, MD 20873 USA.
EM bowersb2@mail.nih.gov
FU Division for Intramural Research, NICHD
FX This research was supported by the Division for Intramural Research,
NICHD. We thank Consuel Ionica and Craig Abbott for help in data
collection and analysis.
NR 27
TC 6
Z9 6
U1 2
U2 19
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7036
J9 J COMP PSYCHOL
JI J. Comp. Psychol.
PD AUG
PY 2012
VL 126
IS 3
BP 318
EP 323
DI 10.1037/a0025081
PG 6
WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology
SC Behavioral Sciences; Psychology; Zoology
GA 991DJ
UT WOS:000307681400012
PM 21842981
ER
PT J
AU Simmons, HE
Dunham, JP
Stack, JC
Dickins, BJA
Pagan, I
Holmes, EC
Stephenson, AG
AF Simmons, H. E.
Dunham, J. P.
Stack, J. C.
Dickins, B. J. A.
Pagan, I.
Holmes, E. C.
Stephenson, A. G.
TI Deep sequencing reveals persistence of intra- and inter-host genetic
diversity in natural and greenhouse populations of zucchini yellow
mosaic virus
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID APHID TRANSMISSIBILITY; INCLUSION-BODIES; COAT PROTEIN; DWARF VIRUS;
POTYVIRUS; EVOLUTION; BOTTLENECKS; DYNAMICS; WHEAT; SELECTION
AB The genetic diversity present in populations of RNA viruses is likely to be strongly modulated by aspects of their life history, including mode of transmission. However, how transmission mode shapes patterns of intra- and inter-host genetic diversity, particularly when acting in combination with de novo mutation, population bottlenecks and the selection of advantageous mutations, is poorly understood. To address these issues, this study performed ultradeep sequencing of zucchini yellow mosaic virus in a wild gourd, Cucurbita pepo ssp. texana, under two infection conditions: aphid vectored and mechanically inoculated, achieving a mean coverage of approximately 10 000x. It was shown that mutations persisted during inter-host transmission events in both the aphid vectored and mechanically inoculated populations, suggesting that the vector-imposed transmission bottleneck is not as extreme as previously supposed. Similarly, mutations were found to persist within individual hosts, arguing against strong systemic bottlenecks. Strikingly, mutations were seen to go to fixation in the aphid-vectored plants, suggestive of a major fitness advantage, but remained at low frequency in the mechanically inoculated plants. Overall, this study highlights the utility of ultradeep sequencing in providing high-resolution data capable of revealing the nature of virus evolution, particularly as the full spectrum of genetic diversity within a population may not be uncovered without sequence coverage of at least 2500-fold.
C1 [Simmons, H. E.; Stack, J. C.; Pagan, I.; Holmes, E. C.; Stephenson, A. G.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Simmons, H. E.] Iowa State Univ, Seed Sci Ctr, Ames, IA 50011 USA.
[Dunham, J. P.] Univ So Calif, Los Angeles, CA 90033 USA.
[Dickins, B. J. A.] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA.
[Dickins, B. J. A.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Pagan, I.] Univ Politecn Madrid, Ctr Biotecnol & Genom Plantas UPM INIA, Pozuelo De Alarcon 28223, Madrid, Spain.
[Holmes, E. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Simmons, HE (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM hsimmons@iastate.edu
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Dickins,
Benjamin/0000-0002-0866-6232; Holmes, Edward/0000-0001-9596-3552
FU National Science Foundation [1010881]; USDA National Institute of Food
and Agriculture [2009-33120-20093]
FX This work was supported by the National Science Foundation Doctorial
Dissertation Grant Program grant no. 1010881, and the Biotechnology Risk
Assessment Program grant no. 2009-33120-20093 from the USDA National
Institute of Food and Agriculture. We thank Tony Omeis for assistance
and use of the Biology Greenhouse, and R. Oberheim and his staff for use
of the Horticulture Farm at the Penn State Agriculture Experiment
Station at Rock Springs, PA, USA.
NR 50
TC 10
Z9 10
U1 0
U2 14
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD AUG
PY 2012
VL 93
BP 1831
EP 1840
DI 10.1099/vir.0.042622-0
PN 8
PG 10
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 992AD
UT WOS:000307746100024
PM 22592263
ER
PT J
AU Gao, B
Wang, H
Lafdil, F
Feng, DC
AF Gao, Bin
Wang, Hua
Lafdil, Fouad
Feng, Dechun
TI STAT proteins - Key regulators of anti-viral responses, inflammation,
and tumorigenesis in the liver
SO JOURNAL OF HEPATOLOGY
LA English
DT Review
DE HCV; Interferon; Liver injury; Liver regeneration; Liver tumor
ID HEPATITIS-C VIRUS; CELL-MEDIATED HEPATITIS; NATURAL-KILLER-CELLS; HUMAN
HEPATOCELLULAR-CARCINOMA; INTERFERON-LAMBDA 1; IL-12 GENE-THERAPY;
SIGNAL TRANSDUCER; TRANSCRIPTION 3; ISCHEMIA/REPERFUSION INJURY;
PARTIAL-HEPATECTOMY
AB Since its discovery in the early 1990s, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway has been found to play key roles in regulating many key cellular processes such as survival, proliferation, and differentiation. There are seven known mammalian STAT family members: STAT1, 2, 3, 4, 5a, 5b, and 6. In the liver, activation of these STAT proteins is critical for anti-viral defense against hepatitis viral infection and for controlling injury, repair, inflammation, and tumorigenesis. The identification of functions for these STAT proteins has increased our understanding of liver disease pathophysiology and treatments, while also suggesting new therapeutic modalities for managing liver disease. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Gao, Bin; Wang, Hua; Feng, Dechun] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Lafdil, Fouad] INSERM, Lab Liver Pathophysiol, U955, F-94000 Creteil, France.
[Lafdil, Fouad] Univ Paris Est, Fac Med, UMR S955, F-94000 Creteil, France.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
FU NIH Institutes of Health; NIAAA, NIH
FX The underlying research reported in this study was funded by the NIH
Institutes of Health.; The work described here from Dr. Bin Gao's
laboratory was supported by the intramural program of the NIAAA, NIH.
NR 137
TC 45
Z9 51
U1 1
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD AUG
PY 2012
VL 57
IS 2
BP 430
EP 441
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 991EW
UT WOS:000307685300029
PM 22504331
ER
PT J
AU Pearce, EJ
Caspar, P
Grzych, JM
Lewis, FA
Sher, A
AF Pearce, Edward J.
Caspar, Patricia
Grzych, Jean-Marie
Lewis, Fred A.
Sher, Alan
TI Downregulation of Th1 Cytokine Production Accompanies Induction of Th2
Responses by a Parasitic Helminth, Schistosoma mansoni
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL CLONE; PROTECTIVE IMMUNITY; MONOCLONAL-ANTIBODIES;
GRANULOMA-FORMATION; MICE; INFECTIONS; RESISTANCE; MOUSE; EGGS;
INTERLEUKIN-5
AB In the mouse, infection with Schistosoma mansoni results in an egg-producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence of egg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL-5) production by T cells from infected mice and interferon gamma (IFN-gamma) synthesis by cells from vaccinated animals (7), suggested differential CD4(+) subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-gamma and IL-2 (secreted by Th1 cells) as compared with IL-4 and IL-5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Th1 lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Th1 reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Th1 responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Th1 function accompanied by a coincident expression of Th2 responses. Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Th1 function. This previously unrecognized downregulation of Th1 cytokine production may be an important immunological consequence of helminth infection related to host adaptation.
C1 [Pearce, Edward J.; Caspar, Patricia; Grzych, Jean-Marie; Sher, Alan] NIAID, Parasit Dis Lab, Immunol & Cell Biol Sect, Bethesda, MD 20892 USA.
[Lewis, Fred A.] Biomed Res Inst, Rockville, MD 20852 USA.
RP Pearce, EJ (reprint author), NIAID, Parasit Dis Lab, Immunol & Cell Biol Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU National Institutes of Health [A1-16006]
FX F. A. Lewis is supported by National Institutes of Health grant
A1-16006.
NR 38
TC 3
Z9 3
U1 1
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1104
EP 1111
PG 8
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100004
PM 22815380
ER
PT J
AU Lesourne, R
Zvezdova, E
Song, KD
El-Khoury, D
Uehara, S
Barr, VA
Samelson, LE
Love, PE
AF Lesourne, Renaud
Zvezdova, Ekaterina
Song, Ki-Duk
El-Khoury, Dalal
Uehara, Shoji
Barr, Valarie A.
Samelson, Lawrence E.
Love, Paul E.
TI Interchangeability of Themis1 and Themis2 in Thymocyte Development
Reveals Two Related Proteins with Conserved Molecular Function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CELL ANTIGEN RECEPTOR; T-CELLS; PHOSPHOLIPASE C-GAMMA-1; NEGATIVE
REGULATION; POSITIVE SELECTION; ACTIVATION; GRB2; VAV; LAT; EXPRESSION
AB Themis1, a recently identified T cell protein, has a critical function in the generation of mature CD4(+)CD8(-) and CD4(-)CD8(+) (CD4 and CD8 single-positive [SP]) thymocytes and T cells. Although Themis1 has been shown to bind to the adaptor proteins LAT and Grb2, previous studies have yielded conflicting results regarding whether thymocytes from Themis1(-/-) mice exhibit TCR-mediated signaling defects. In this study, we demonstrate that, in the absence of Themis1, TCR-mediated signaling is selectively impaired in CD4 SP and CD8 SP thymocytes but is not affected in CD4(+)CD8(+) double-positive thymocytes despite high expression of Themis1 in double-positive thymocytes. Like Themis1, Themis2, a related member of the Themis family, which is expressed in B cells and macrophages, contains two conserved cysteine-based domains, a proline-rich region, and a nuclear localization signal. To determine whether Themis1 and Themis2 can perform similar functions in vivo, we analyzed T cell development and TCR-mediated signaling in Themis1(-/-) mice reconstituted with either Themis1 or Themis2 transgenes. Notably, Themis1 and Themis2 exhibited the same potential to restore T cell development and TCR-mediated signaling in Themis1(-/-) mice. Both proteins were tyrosine phosphorylated and were recruited within Grb2 signaling complexes to LAT following TCR engagement. These results suggest that conserved molecular features of the Themis1 and Themis2 proteins are important for their biological activity and predict that Themis1 and Themis2 may perform similar functions in T and B cells, respectively. The Journal of Immunology, 2012, 189: 1154-1161.
C1 [Lesourne, Renaud; Zvezdova, Ekaterina; Song, Ki-Duk; El-Khoury, Dalal; Uehara, Shoji; Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Barr, Valarie A.; Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Love, PE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, 9000 Rockville Pike,Bldg 6B,Room 2B210,MSC 2780, Bethesda, MD 20892 USA.
EM lovep@mail.nih.gov
RI Lesourne, Renaud/M-1855-2014; Zvezdova, Ekaterina/N-7860-2015
FU National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Cancer Institute
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, and the National Cancer
Institute.
NR 39
TC 14
Z9 14
U1 0
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1154
EP 1161
DI 10.4049/jimmunol.1200123
PG 8
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100011
PM 22732588
ER
PT J
AU Shi, GP
Lovaas, JD
Tan, CY
Vistica, BP
Wawrousek, EF
Aziz, MK
Rigden, RC
Caspi, RR
Gery, I
AF Shi, Guangpu
Lovaas, Jenna D.
Tan, Cuiyan
Vistica, Barbara P.
Wawrousek, Eric F.
Aziz, Mehak K.
Rigden, Rachael C.
Caspi, Rachel R.
Gery, Igal
TI Cell-Cell Interaction with APC, not IL-23, Is Required for Naive CD4
Cells To Acquire Pathogenicity during Th17 Lineage Commitment
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IL-17-PRODUCING T-CELLS; NEO-SELF ANTIGEN; AUTOIMMUNE ENCEPHALOMYELITIS;
CYTOKINE PRODUCTION; TGF-BETA; INFLAMMATION; RECEPTOR; DISTINCT; IL-17;
MECHANISMS
AB Subpopulations of pathogenic or nonpathogenic Th17 cells were reported to develop when presensitized CD4 cells were activated with their target Ag during polarization by either IL-23 or IL-6 and TGF-beta, respectively. In this study, we generated two Th17 subpopulations by using a system in which naive CD4 cells from TCR transgenic mice specific to hen egg lysozyme (HEL) are polarized with IL-6/TGF-beta and, concurrently, are activated either with HEL presented by APCs, or with anti-CD3/CD28 Abs. Only the former cells were pathogenic, inducing inflammation in eyes expressing HEL. Naive CD4 cells activated by the anti-CD3/CD28 Abs acquired pathogenicity, however, when cocultured with HEL/APC. Importantly, the naive CD4 cells did not acquire pathogenicity when cocultured with APCs stimulated with LPS or when separated from the HEL-presenting cells by a semipermeable membrane. Unlike with presensitized Th17, soluble IL-23 does not participate in pathogenicity acquisition by naive CD4 cells; no pathogenicity was induced by adding IL-23 to cultures activated with anti-CD3/CD28 Abs. Furthermore, Abs against IL-23 or IL-23R did not inhibit acquisition of pathogenicity in cultures of naive CD4 cells activated by HEL/APC. Our data thus show that, unlike presensitized CD4 cells, naive CD4 cells polarized toward Th17 phenotype acquire pathogenicity only by direct interaction with APCs presenting the Ag, with no apparent involvement of soluble IL-23. We suggest that the Th17 lymphocytes derived from naive CD4 cells participate in pathogenic and other immune processes, along with the IL-23-dependent Th17 cells. The Journal of Immunology, 2012, 189: 1220-1227.
C1 [Shi, Guangpu; Lovaas, Jenna D.; Tan, Cuiyan; Vistica, Barbara P.; Aziz, Mehak K.; Rigden, Rachael C.; Caspi, Rachel R.; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wawrousek, Eric F.] NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N208, Bethesda, MD 20892 USA.
EM geryi@nei.nih.gov
OI Caspi, Rachel/0000-0002-7140-7671
FU National Eye Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Eye Institute, National Institutes of Health.
NR 34
TC 9
Z9 10
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1220
EP 1227
DI 10.4049/jimmunol.1103033
PG 8
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100018
PM 22745380
ER
PT J
AU Punwani, D
Simon, K
Choi, Y
Dutra, A
Gonzalez-Espinosa, D
Pak, E
Naradikian, M
Song, CH
Zhang, J
Bodine, DM
Puck, JM
AF Punwani, Divya
Simon, Karen
Choi, Youngnim
Dutra, Amalia
Gonzalez-Espinosa, Diana
Pak, Evgenia
Naradikian, Martin
Song, Chang-Hwa
Zhang, Jenny
Bodine, David M.
Puck, Jennifer M.
TI Transcription Factor Zinc Finger and BTB Domain 1 Is Essential for
Lymphocyte Development
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL DEVELOPMENT; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; KINASE
CATALYTIC SUBUNIT; HEMATOPOIETIC STEM-CELL; B-CELL; LINEAGE COMMITMENT;
NONSENSE MUTATION; MOUSE; PROTEIN; GENE
AB Absent T lymphocytes were unexpectedly found in homozygotes of a transgenic mouse from an unrelated project. T cell development did not progress beyond double-negative stage 1 thymocytes, resulting in a hypocellular, vestigial thymus. B cells were present, but NK cell number and B cell isotype switching were reduced. Transplantation of wild-type hematopoietic cells corrected the defect, which was traced to a deletion involving five contiguous genes at the transgene insertion site on chromosome 12C3. Complementation using bacterial artificial chromosome transgenesis implicated zinc finger BTB-POZ domain protein 1 (Zbtb1) in the immunodeficiency, confirming its role in T cell development and suggesting involvement in B and NK cell differentiation. Targeted disruption of Zbtb1 recapitulated the T-B+NK- SCID phenotype of the original transgenic animal. Knockouts for Zbtb1 had expanded populations of bone marrow hematopoietic stem cells and also multipotent and early lymphoid lineages, suggesting a differentiation bottleneck for common lymphoid progenitors. Expression of mRNA encoding Zbtb1, a predicted transcription repressor, was greatest in hematopoietic stem cells, thymocytes, and pre-B cells, highlighting its essential role in lymphoid development. The Journal of Immunology, 2012, 189: 1253-1264.
C1 [Punwani, Divya; Gonzalez-Espinosa, Diana; Naradikian, Martin; Song, Chang-Hwa; Zhang, Jenny; Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Simon, Karen; Dutra, Amalia; Pak, Evgenia; Bodine, David M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Choi, Youngnim] Seoul Natl Univ, Sch Dent, Dept Oromaxillofacial Infect & Immun, Seoul 110744, South Korea.
[Naradikian, Martin] Univ Penn, Philadelphia, PA 19104 USA.
[Song, Chang-Hwa] Chungnam Natl Univ, Coll Med, Dept Microbiol, Taejon 301747, South Korea.
RP Puck, JM (reprint author), Univ Calif San Francisco, Dept Pediat, Box 0519,513 Parnassus Ave,HSE 301A, San Francisco, CA 94143 USA.
EM puckj@peds.ucsf.edu
OI Naradikian, Martin/0000-0003-1926-0382
FU National Institutes of Health [R01 AI078248]; Division of Intramural
Research, National Human Genome Research Institute, National Institutes
of Health
FX This work was supported in part by National Institutes of Health Grant
R01 AI078248 (to J.M.P.) and by the Division of Intramural Research,
National Human Genome Research Institute, National Institutes of Health.
NR 59
TC 7
Z9 9
U1 1
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1253
EP 1264
DI 10.4049/jimmunol.1200623
PG 12
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100022
PM 22753936
ER
PT J
AU Mage, MG
Dolan, MA
Wang, R
Boyd, LF
Revilleza, MJ
Robinson, H
Natarajan, K
Myers, NB
Hansen, TH
Margulies, DH
AF Mage, Michael G.
Dolan, Michael A.
Wang, Rui
Boyd, Lisa F.
Revilleza, Maria Jamela
Robinson, Howard
Natarajan, Kannan
Myers, Nancy B.
Hansen, Ted H.
Margulies, David H.
TI The Peptide-Receptive Transition State of MHC Class I Molecules: Insight
from Structure and Molecular Dynamics
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; HLA-DM; ENDOPLASMIC-RETICULUM;
ANTIGENIC PEPTIDES; CELL-SURFACE; CONFORMATIONAL FLEXIBILITY;
MONOCLONAL-ANTIBODIES; TAPASIN DEPENDENCE; QUALITY-CONTROL;
HYDROGEN-BOND
AB MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed "open" position in the PR transition state to a "closed" position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation. The Journal of Immunology, 2012, 189: 1391-1399.
C1 [Mage, Michael G.; Wang, Rui; Boyd, Lisa F.; Revilleza, Maria Jamela; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael A.] NIAID, Computat Biol Sect, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
[Robinson, Howard] Brookhaven Natl Labs, Natl Synchrotron Light Source, Upton, NY 11973 USA.
[Myers, Nancy B.; Hansen, Ted H.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N311, Bethesda, MD 20892 USA.
EM mmage@mail.nih.gov; dhm@nih.gov
RI Margulies, David/H-7089-2013;
OI Margulies, David/0000-0001-8530-7375
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health [AI019687]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, as well as by
National Institutes of Health Grant AI019687 (to T H.H.).
NR 89
TC 20
Z9 20
U1 0
U2 14
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1391
EP 1399
DI 10.4049/jimmunol.1200831
PG 9
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100036
PM 22753930
ER
PT J
AU Yan, CG
Wu, M
Cao, J
Tang, HF
Zhu, M
Johnson, PF
Gao, HW
AF Yan, Chunguang
Wu, Min
Cao, Jay
Tang, Huifang
Zhu, Mei
Johnson, Peter F.
Gao, Hongwei
TI Critical Role for CCAAT/Enhancer-Binding Protein beta in Immune
Complex-Induced Acute Lung Injury
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TRANSCRIPTION FACTORS;
C/EBP-BETA; GENE-EXPRESSION; MESSENGER-RNA; MACROPHAGES; IGG;
ACTIVATION; DELTA
AB C/EBPs, particularly C/EBP beta and C/EBP delta, are known to participate in the regulation of many genes associated with inflammation. However, very little is known regarding the activation and functions of C/EBPb and C/EBPd in acute lung inflammation and injury. In this study, we show that both C/EBP beta and C/EBP delta activation are triggered in lungs and in alveolar macrophages following intrapulmonary deposition of IgG immune complexes. We further show that mice carrying a targeted deletion of the C/EBP beta gene displayed significant attenuation of the permeability index (lung vascular leak of albumin), lung neutrophil accumulation (myeloperoxidase activity), total number of WBCs, and neutrophils in bronchoalveolar lavage fluids compared with wildtype mice. Moreover, the mutant mice expressed considerably less TNF-alpha, IL-6, and CXC/CC chemokine and soluble ICAM-1 proteins in bronchoalveolar lavage fluids, and corresponding mRNAs in the IgG immune complex-injured lung, compared with wild-type mice. These phenotypes were associated with a significant reduction in morphological lung injury. In contrast, C/EBPd deficiency had no effect on IgG immune complex-induced lung injury. IgG immune complex-stimulated C/EBP beta-deficient alveolar macrophages released significantly less TNF-a, IL-6, MIP-2, keratinocyte cell-derived chemokine, and MIP-1 alpha compared with wild-type cells. Similar decreases in IgG immune complex-induced inflammatory mediator production were observed following small interfering RNA ablation of C/EBP beta in a murine alveolar macrophage cell line. These findings implicate C/EBPb as a critical regulator of IgG immune complex-induced inflammatory responses and injury in the lung. The Journal of Immunology, 2012, 189: 1480-1490.
C1 [Yan, Chunguang; Tang, Huifang; Gao, Hongwei] Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA.
[Yan, Chunguang; Wu, Min] Univ N Dakota, Dept Biochem & Mol Biol, Grand Forks, ND 58202 USA.
[Cao, Jay] ARS, USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Zhu, Mei] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Johnson, Peter F.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Gao, HW (reprint author), Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Brigham & Womens Hosp,Med Sch, 20 Shattuck St, Boston, MA 02115 USA.
EM hgao@zeus.bwh.harvard.edu
FU National Institutes of Health Grants [5R01HL092905-04, 3R01HL092905-
02S1]; National Institutes of Health [ES014690]; Flight Attendant
Medical Research Institute [103007]; National Institutes of Health;
National Cancer Institute; Center for Cancer Research; U.S. Department
of Agriculture Agricultural Research Service Current Research
Information System Program [5450-51000-046-00D]
FX This work was supported by National Institutes of Health Grants
5R01HL092905-04 and 3R01HL092905- 02S1 (to H. G.), National Institutes
of Health Grant ES014690, Flight Attendant Medical Research Institute
Grant 103007 (to M. W.), the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research (to P.F.J.), and the U.S. Department of Agriculture
Agricultural Research Service Current Research Information System
Program Grant 5450-51000-046-00D (to J.C.).
NR 43
TC 15
Z9 15
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2012
VL 189
IS 3
BP 1480
EP 1490
DI 10.4049/jimmunol.1200877
PG 11
WC Immunology
SC Immunology
GA 976QJ
UT WOS:000306599100045
PM 22732594
ER
PT J
AU Capurso, G
Festa, S
Valente, R
Piciucchi, M
Panzuto, F
Jensen, RT
Delle Fave, G
AF Capurso, Gabriele
Festa, Stefano
Valente, Roberto
Piciucchi, Matteo
Panzuto, Francesco
Jensen, Robert T.
Delle Fave, Gianfranco
TI Molecular pathology and genetics of pancreatic endocrine tumours
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Review
ID GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; COMPARATIVE GENOMIC
HYBRIDIZATION; EPIDERMAL-GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE;
HETEROZYGOSITY FREQUENTLY OCCURS; ISLET CELL TUMORS; SUPPRESSOR GENE;
MTOR PATHWAY; CHROMOSOMAL ALTERATIONS; THERAPEUTIC TARGETS
AB Pancreatic neuroendocrine tumours (PETs) are the second most frequent pancreatic neoplasms. Their poor chemosensitivity, high rate of metastatic disease and relatively long survival make PETs an ideal field to be explored for novel therapies based on specific molecular changes. PETs are generally sporadic but can also arise within hereditary syndromes, such as multiple endocrine neoplasia type 1, von Hippel-Lindau, neurofibromatosis type 1 and tuberous sclerosis complex, which represent a model for sporadic cases too. Among allelic imbalances, main genomic changes involve gain of 17q, 7q and 20q and loss of 11q, 6q and 11p, which identify regions of putative candidate oncogenes or tumour suppressor genes (TSGs), respectively, sometime with potential prognostic significance. Overexpression of Src-like kinases and cyclin D1 (CCND1) oncogene has been described. As for TSGs, P53 (TP53), DPC4/SMAD4 and RB (RB1) are not implicated in PET tumorigenesis, while for p16INK4a (CDKN2A), TIMP3, RASSF1A and hMLH1, more data are available, suggesting a role for methylation as a silencing mechanism. In the last decade, gene expression profile studies, analysis of microRNAs and, more recently, large-scale mutational analysis have highlighted commonly altered molecular pathways in the pathology of PETs. The roles of the mammalian target of rapamycin pathway, and its connection with Src kinases, and the activity of a number of tyrosine kinase receptors seem to be pivotal, as confirmed by the results of recent clinical trials with targeted agents. Mutations of DAXX and ATRX are common and related to altered telomeres but not to prognosis.
C1 [Capurso, Gabriele; Festa, Stefano; Valente, Roberto; Piciucchi, Matteo; Panzuto, Francesco; Delle Fave, Gianfranco] Univ Roma La Sapienza, S Andrea Hosp, Fac Med & Psychol, Digest & Liver Dis Unit, I-00189 Rome, Italy.
[Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Delle Fave, G (reprint author), Univ Roma La Sapienza, S Andrea Hosp, Fac Med & Psychol, Digest & Liver Dis Unit, Via Grottarossa 1035, I-00189 Rome, Italy.
EM gianfranco.dellefave@uniroma1.it
OI Panzuto, Francesco/0000-0003-2789-4289
FU ITANET (Italian Association for Neuroendocrine Tumours)
FX This review is funded by ITANET (Italian Association for Neuroendocrine
Tumours).
NR 102
TC 27
Z9 29
U1 0
U2 8
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD AUG
PY 2012
VL 49
IS 1
BP R37
EP R50
DI 10.1530/JME-12-0069
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 990KJ
UT WOS:000307629400005
PM 22586144
ER
PT J
AU Diyabalanage, T
Ratnayake, R
Bokesch, HR
Ransom, TT
Henrich, CJ
Beutler, JA
McMahon, JB
Gustafson, KR
AF Diyabalanage, Thushara
Ratnayake, Ranjala
Bokesch, Heidi R.
Ransom, Tanya T.
Henrich, Curtis J.
Beutler, John A.
McMahon, James B.
Gustafson, Kirk R.
TI Flabelliferins A and B, Sesterterpenoids from the South Pacific Sponge
Carteriospongia flabellifera
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID MARINE SPONGE; INDONESIAN SPONGE; INHIBITORS; FOLIASCENS
AB Two new sesterterpenoids named flabelliferins A (1) and B (2) were isolated from the lipophilic extract of the sponge Cateriospongia flabellifera, collected in the South Pacific near Vanuatu. The structure and absolute configuration of these two compounds were assigned by a combination of one- and two-dimensional NMR spectroscopy and by Mosher's ester analysis. Flabelliferin A (1) has a rare 25-homocheilanthane carbon skeleton, while flabelliferin B (2) is a 24-nor-25-homoscalarane sesterterpenoid.
C1 [Diyabalanage, Thushara; Ratnayake, Ranjala; Bokesch, Heidi R.; Ransom, Tanya T.; Henrich, Curtis J.; Beutler, John A.; McMahon, James B.; Gustafson, Kirk R.] Frederick Natl Lab Canc Res, Mol Targets Lab Ctr Canc Res, Frederick, MD 21702 USA.
[Bokesch, Heidi R.; Henrich, Curtis J.] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA.
RP Gustafson, KR (reprint author), Frederick Natl Lab Canc Res, Mol Targets Lab Ctr Canc Res, Frederick, MD 21702 USA.
EM gustafki@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU NIH, Frederick National Laboratory for Cancer Research, Center for
Cancer Research; Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]
FX We gratefully acknowledge D. Newman (NCI) and T. McCloud
(SAIC-Frederick) for the sponge extracts and M. Dyba and S. Tarasov
(Biophysics Resource, Structural Biophysics Laboratory, CCR) for
assistance in acquiring high-resolution mass spectra. This research was
supported in part by the Intramural Research Program of NIH, Frederick
National Laboratory for Cancer Research, Center for Cancer Research.
This project has been funded in whole or in part with Federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health, under contract HHSN261200800001E. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 20
TC 6
Z9 7
U1 2
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD AUG
PY 2012
VL 75
IS 8
BP 1490
EP 1494
DI 10.1021/np3003518
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 992TT
UT WOS:000307803300011
PM 22834941
ER
PT J
AU Goffart, L
Hafed, ZM
Krauzlis, RJ
AF Goffart, Laurent
Hafed, Ziad M.
Krauzlis, Richard J.
TI Visual Fixation as Equilibrium: Evidence from Superior Colliculus
Inactivation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SACCADIC EYE-MOVEMENTS; STEM OMNIPAUSE NEURONS; CAUDAL FASTIGIAL
NUCLEUS; REVERSIBLE INACTIVATION; RHESUS-MONKEY; GAZE SHIFTS; TARGET
SELECTION; SMOOTH-PURSUIT; DISCHARGE CHARACTERISTICS; MUSCIMOL
INACTIVATION
AB During visual fixation, the image of an object is maintained within the fovea. Previous studies have shown that such maintenance involves the deep superior colliculus (dSC). However, the mechanisms by which the dSC supports visual fixation remain controversial. According to one view, activity in the rostral dSC maintains gaze direction by preventing neurons in the caudal dSC from issuing saccade commands. An alternative hypothesis proposes that gaze direction is achieved through equilibrium of target position signals originating from the two dSCs. Here, we show in monkeys that artificially reducing activity in the rostral half of one dSC results in a biased estimate of target position during fixation, consistent with the second hypothesis, rather than an inability to maintain gaze fixation as predicted by the first hypothesis. After injection of muscimol at rostral sites in the dSC, fixation became more stable since microsaccade rate was reduced rather than increased. Moreover, the scatter of eye positions was offset relative to preinactivation baselines. The magnitude and the direction of the offsets depended on both the target size and the injected site in the collicular map. Other oculomotor parameters, such as the accuracy of saccades to peripheral targets and the amplitude and velocity of fixational saccades, were largely unaffected. These results suggest that the rostral half of the dSC supports visual fixation through a distributed representation of behaviorally relevant target position signals. The inactivation-induced fixation offset establishes the foveal visual stimulation that is required to restore the balance of activity between the two dSCs.
C1 [Goffart, Laurent] Aix Marseille Univ, Ctr Natl Rech Sci, UMR 7289, Inst Neurosci Timone, F-13385 Marseille 5, France.
[Hafed, Ziad M.] Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
[Krauzlis, Richard J.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
[Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Goffart, L (reprint author), Aix Marseille Univ, Ctr Natl Rech Sci, UMR 7289, Inst Neurosci Timone, Campus Sante,27 Blvd Jean Moulin, F-13385 Marseille 5, France.
EM laurent.goffart@univ-amu.fr
FU Centre National de la Recherche Scientifique, Agence Nationale de la
Recherche Grant RETINAE; Centre National de la Recherche Scientifique,
Agence Nationale de la Recherche Grant VISAFIX; Werner Reichardt Centre
for Integrative Neuroscience; Natural Sciences and Engineering Research
Council of Canada; Sloan-Swartz Center for Theoretical Neurobiology, NIH
[EY12212]; National Eye Institute Intramural Research Program at the NIH
FX This work was supported by the Centre National de la Recherche
Scientifique, Agence Nationale de la Recherche Grants RETINAE and
VISAFIX (L.G.), the Werner Reichardt Centre for Integrative
Neuroscience, the Natural Sciences and Engineering Research Council of
Canada, the Sloan-Swartz Center for Theoretical Neurobiology, NIH Grants
EY12212 (Z.M.H.) and EY12212 (R.J.K.), and the National Eye Institute
Intramural Research Program at the NIH (R.J.K.). We are grateful for the
help of Natalie Dill in the experiments and Laurent Madelain in the data
analysis.
NR 72
TC 30
Z9 30
U1 0
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 1
PY 2012
VL 32
IS 31
BP 10627
EP 10636
DI 10.1523/JNEUROSCI.0696-12.2012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 983NL
UT WOS:000307125900020
PM 22855812
ER
PT J
AU Liang, J
Wang, DM
Renaud, G
Wolfsberg, TG
Wilson, AF
Burgess, SM
AF Liang, Jin
Wang, Dongmei
Renaud, Gabriel
Wolfsberg, Tyra G.
Wilson, Alexander F.
Burgess, Shawn M.
TI The stat3/socs3a Pathway Is a Key Regulator of Hair Cell Regeneration in
Zebrafish stat3/socs3a Pathway: Regulator of Hair Cell Regeneration
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LATERAL-LINE SYSTEM; INNER-EAR; LIVER-REGENERATION; DANIO-RERIO; SERINE
PHOSPHORYLATION; SIGNAL TRANSDUCER; COCHLEAR CHANGES; ACOUSTIC TRAUMA;
LASER-ABLATION; HEARING-LOSS
AB All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993; Baird et al., 1996), but mammals possess only a very limited capacity for regeneration after birth (Roberson and Rubel, 1994). As a result, mammals experience permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique digital gene expression, which leverages the power of next-generation sequencing ('t Hoen et al., 2008). We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological inhibition of stat3 signaling accelerated hair cell regeneration without overproducing cells. Taking other published datasets into account (Sano et al., 1999; Schebesta et al., 2006; Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009), we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.
C1 [Liang, Jin; Renaud, Gabriel; Wolfsberg, Tyra G.; Burgess, Shawn M.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Liang, Jin; Renaud, Gabriel; Wolfsberg, Tyra G.; Burgess, Shawn M.] NHGRI, Inherited Dis Res Branch, Bethesda, MD 20892 USA.
[Liang, Jin] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA.
[Wang, Dongmei] Chinese Acad Sci, Qingdao Inst BioEnergy & BioProcess Technol, Qingdao 266101, Shandong, Peoples R China.
RP Burgess, SM (reprint author), NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
RI zheng, yonghong/H-3700-2012;
OI Burgess, Shawn/0000-0003-1147-0596
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health
(S.M.B.). We thank A. Popper for use of the sound exposure equipment and
helpful discussions, and D. Bodine and W. Pavan for critical reading of
the manuscript.
NR 76
TC 33
Z9 36
U1 0
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 1
PY 2012
VL 32
IS 31
BP 10662
EP 10673
DI 10.1523/JNEUROSCI.5785-10.2012
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 983NL
UT WOS:000307125900023
PM 22855815
ER
PT J
AU Groninger, H
Schisler, RE
AF Groninger, Hunter
Schisler, Randall E.
TI Topical Capsaicin for Neuropathic Pain #255
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Editorial Material
ID PATCH
C1 [Groninger, Hunter] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Groninger, H (reprint author), NIH, Ctr Clin, Bldg 10,Room 2-1733, Bethesda, MD 20892 USA.
EM hunter.groninger@nih.gov
NR 4
TC 6
Z9 7
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD AUG
PY 2012
VL 15
IS 8
BP 946
EP 947
DI 10.1089/jpm.2012.9571
PG 2
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 983CV
UT WOS:000307095200017
PM 22849599
ER
PT J
AU Buchowski, MS
Matthews, CE
Cohen, SS
Signorello, LB
Fowke, JH
Hargreaves, MK
Schlundt, DG
Blot, WJ
AF Buchowski, Maciej S.
Matthews, Charles E.
Cohen, Sarah S.
Signorello, Lisa B.
Fowke, Jay H.
Hargreaves, Margaret K.
Schlundt, David G.
Blot, William J.
TI Evaluation of a Questionnaire to Assess Sedentary and Active Behaviors
in the Southern Community Cohort Study
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE physical activity questionnaire; low income; reliability;
reproducibility
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; RT3 TRIAXIAL ACCELEROMETER; TELEVISION
VIEWING TIME; TEST-RETEST RELIABILITY; ENERGY-EXPENDITURE; HEALTH
DISPARITIES; AFRICAN-AMERICANS; MEASUREMENT ERROR; ACTIVITY RECALL;
WOMENS HEALTH
AB Background: Low physical activity (PA) is linked to cancer and other diseases prevalent in racial/ethnic minorities and low-income populations. This study evaluated the PA questionnaire (PAQ) used in the Southern Cohort Community Study, a prospective investigation of health disparities between African-American and white adults. Methods: The PAQ was administered upon entry into the cohort (PAQ1) and after 12-15 months (PAQ2) in 118 participants (40-60 year-old, 48% male, 74% African-American). Test-retest reliability (PAQ1 versus PAQ2) was assessed using Spearman correlations and the Wilcoxon signed rank test. Criterion validity of the PAQ was assessed via comparison with a PA monitor and a last-month PA survey (LMPAS), administered up to 4 times in the study period. Results: The PAQ test-retest reliability ranged from 0.25-0.54 for sedentary behaviors and 0.22-0.47 for active behaviors. The criterion validity for the PAQ compared with PA monitor ranged from 0.21-0.24 for sedentary behaviors and from 0.17-0.31 for active behaviors. There was general consistency in the magnitude of correlations between the PAQ and PA-monitor between African-Americans and whites. Conclusions: The SCCS-PAQ has fair to moderate test-retest reliability and demonstrated some evidence of criterion validity for ranking participants by their level of sedentary and active behaviors.
C1 [Buchowski, Maciej S.; Signorello, Lisa B.; Fowke, Jay H.; Blot, William J.] Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN 37235 USA.
[Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
[Cohen, Sarah S.; Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Cohen, Sarah S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Signorello, Lisa B.; Fowke, Jay H.; Blot, William J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Hargreaves, Margaret K.] Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA.
[Schlundt, David G.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
RP Buchowski, MS (reprint author), Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN 37235 USA.
RI Buchowski, Maciej/A-2683-2008; matthews, Charles/E-8073-2015
OI Buchowski, Maciej/0000-0002-0566-1743; matthews,
Charles/0000-0001-8037-3103
FU NCATS NIH HHS [KL2 TR000446]; NCI NIH HHS [R01 CA092447]; NCRR NIH HHS
[KL2 RR024977, TL1 RR024978, UL1 RR024975]; NIDDK NIH HHS [DK20593, P30
DK020593, P30 DK058404, P60 DK020593, R01 DK069465, R01 DK69465]
NR 45
TC 5
Z9 5
U1 2
U2 9
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 AUG
PY 2012
VL 9
IS 6
BP 765
EP 775
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 992AS
UT WOS:000307747800002
PM 21952413
ER
PT J
AU Ramulu, PY
Chan, ES
Loyd, TL
Ferrucci, L
Friedman, DS
AF Ramulu, Pradeep Y.
Chan, Emilie S.
Loyd, Tara L.
Ferrucci, Luigi
Friedman, David S.
TI Comparison of Home and Away-From-Home Physical Activity Using
Accelerometers and Cellular Network-Based Tracking Devices
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE outdoors; measurement; built environment; geographic information systems
ID GLOBAL POSITIONING SYSTEM; OLDER-ADULTS; MORTALITY; LOCATION; RISK;
TIME; LIFE; BEHAVIORS
AB Background: Measuring physical at home and away from home is essential for assessing health and well-being, and could help design interventions to increase physical activity. Here, we describe how physical activity at home and away from home can be quantified by combining information from cellular network-based tracking devices and accelerometers. Methods: Thirty-five working adults wore a cellular network-based tracking device and an accelerometer for 6 consecutive days and logged their travel away from home. Performance of the tracking device was determined using the travel log for reference. Tracking device and accelerometer data were merged to compare physical activity at home and away from home. Results: The tracking device detected 98.6% of all away-from-home excursions, accurately measured time away from home and demonstrated few prolonged signal drop-out periods. Most physical activity took place away from home on weekdays, but not on weekends. Subjects were more physically active per unit of time while away from home, particularly on weekends. Conclusions: Cellular network-based tracking devices represent an alternative to global positioning systems for tracking location, and provide information easily integrated with accelerometers to determine where physical activity takes place. Promoting greater time spent away from home may increase physical activity.
C1 [Ramulu, Pradeep Y.; Chan, Emilie S.; Loyd, Tara L.; Friedman, David S.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA.
RP Ramulu, PY (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
FU NEI NIH HHS [K12 EY015025, K23 EY018595]
NR 35
TC 6
Z9 6
U1 1
U2 4
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 AUG
PY 2012
VL 9
IS 6
BP 809
EP 817
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 992AS
UT WOS:000307747800007
PM 21952052
ER
PT J
AU Courneya, KS
Karvinen, KH
McNeely, ML
Campbell, KL
Brar, S
Woolcott, CG
McTiernan, A
Ballard-Barbash, R
Friedenreich, CM
AF Courneya, Kerry S.
Karvinen, Krishna H.
McNeely, Margaret L.
Campbell, Kristin L.
Brar, Sony
Woolcott, Christy G.
McTiernan, Anne
Ballard-Barbash, Rachel
Friedenreich, Christine M.
TI Predictors of Adherence to Supervised and Unsupervised Exercise in the
Alberta Physical Activity and Breast Cancer Prevention Trial
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE exercise determinants; motivation; randomized controlled trial; theory
of planned behavior
ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; OLDER-ADULTS;
CHEMOTHERAPY; MAINTENANCE; BEHAVIOR
AB Background: Few studies have examined the predictors of adherence separately for supervised and unsupervised exercise or in postmenopausal women over an extended time period. Here, we report the predictors of exercise adherence in the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial. Methods: The ALPHA trial randomized 160 postmenopausal women in Calgary and Edmonton, Canada to an exercise intervention that consisted of an average of 200 min/wk of supervised (123 minutes) and unsupervised (77 minutes) exercise over a 1-year period. Baseline data were collected on demographic, health-related fitness, quality of life, and motivational variables from the theory of planned behavior. Results: Participants completed an average of 95% of their supervised exercise and 79% of their unsupervised exercise. In multivariate analyses, 8.1% (P = .001) of the variance was explained for supervised exercise by being from Edmonton (beta = 0.22; P = .004) and older (beta = 0.15; P =.050). For unsupervised exercise, 21.1% (P < .001) of the variance was explained by being from Calgary (beta = -0.39; P < .001), having a family history of breast cancer (beta = 0.21; P = .003), and having higher vitality (beta = 0.19; P = .011). Conclusions: Predictors of adherence may differ for supervised and unsupervised exercise, moreover, predicting adherence to supervised exercise may be particularly difficult in well-controlled efficacy trials.
C1 [Courneya, Kerry S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada.
[Karvinen, Krishna H.] E Carolina Univ, Dept Exercise Sci, Durham, NC USA.
[McNeely, Margaret L.] Univ Alberta, Dept Rehabil Med, Edmonton, AB, Canada.
[Campbell, Kristin L.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V5Z 1M9, Canada.
[Brar, Sony; Friedenreich, Christine M.] Alberta Hlth Serv, Dept Populat Hlth, Calgary, AB, Canada.
[Woolcott, Christy G.] Dalhousie Univ, Dept Epidemiol, Halifax, NS, Canada.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Prevent Ctr, Seattle, WA 98104 USA.
[Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MA USA.
RP Courneya, KS (reprint author), Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada.
FU Canadian Institutes of Health Research
NR 16
TC 12
Z9 14
U1 2
U2 25
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 AUG
PY 2012
VL 9
IS 6
BP 857
EP 866
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 992AS
UT WOS:000307747800012
PM 21953311
ER
PT J
AU Tang, WK
Xia, D
AF Tang, Wai Kwan
Xia, Di
TI Structural and functional deviations in disease-associated p97 mutants
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Review
DE p97; VCP; IBMPFD; AAA protein; Structure and function
ID INCLUSION-BODY MYOPATHY; VALOSIN-CONTAINING-PROTEIN;
RETICULUM-ASSOCIATED DEGRADATION; AAA ATPASE P97/VCP;
UBIQUITIN-SELECTIVE CHAPERONE; FRONTOTEMPORAL DEMENTIA;
ENDOPLASMIC-RETICULUM; PAGET-DISEASE; CONFORMATIONAL-CHANGES;
MEMBRANE-FUSION
AB Missense mutations that occur at the interface between two functional domains in the AAA protein p97 lead to suboptimal performance in its enzymatic activity and impaired intracellular functions, causing human disorders such as inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). Much progress has been made in characterizing these mutants at cellular, sub-cellular and molecular levels, gaining a substantial understanding of the involvement of p97 in various cellular pathways. At the tissue level, patient biopsies revealed co-localization of p97 with pathologic proteineous inclusions and rimmed vacuoles, which can be reproduced in various cellular and animal models of IBMPFD. At the subcellular level, alterations in p97's ability to bind various adaptor proteins have been demonstrated for some but not all binding partners. Biochemical and biophysical characterizations of pathogenic p97 revealed altered nucleotide binding properties in the D1-domains compared to the wild type. Structural studies showed that mutant p97 are capable of undergoing a uniform transition in the N-domain from a Down- to an Up-conformation in the presence of ATPyS, while in the wild-type p97, this conformational change can only be demonstrated in solutions but not in crystals. These structural and biochemical analyses of IBMPFD mutants shed new light into the mechanism of p97 function. Published by Elsevier Inc.
C1 [Tang, Wai Kwan; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2122C, Bethesda, MD 20892 USA.
EM dixia@helix.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. We thank
George Leiman for editorial assistance during the preparation of this
manuscript.
NR 87
TC 10
Z9 10
U1 0
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD AUG
PY 2012
VL 179
IS 2
SI SI
BP 83
EP 92
DI 10.1016/j.jsb.2012.04.024
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 987JT
UT WOS:000307413900003
PM 22579784
ER
PT J
AU Hodin, R
Angelos, P
Carty, S
Chen, H
Clark, O
Doherty, G
Duh, QY
Evans, DB
Heller, K
Inabnet, W
Kebebew, E
Pasieka, J
Perrier, N
Sturgeon, C
AF Hodin, Richard
Angelos, Peter
Carty, Sally
Chen, Herb
Clark, Orlo
Doherty, Gerard
Duh, Quan-Yang
Evans, Douglas B.
Heller, Keith
Inabnet, William
Kebebew, Electron
Pasieka, Janice
Perrier, Nancy
Sturgeon, Cord
TI No Need to Abandon Unilateral Parathyroid Surgery
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Letter
C1 [Hodin, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Angelos, Peter] Univ Chicago, Chicago, IL 60637 USA.
[Carty, Sally] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Chen, Herb] Univ Wisconsin, Madison, WI 53706 USA.
[Clark, Orlo; Duh, Quan-Yang] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Doherty, Gerard] Boston Univ, Boston, MA 02215 USA.
[Evans, Douglas B.] Med Coll Wisconsin, Milwaukee, WI USA.
[Heller, Keith] NYU, Langone Med Ctr, New York, NY 10003 USA.
[Inabnet, William] Mt Sinai Sch Med, New York, NY USA.
[Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
[Pasieka, Janice] Univ Calgary, Calgary, AB T2N 1N4, Canada.
[Sturgeon, Cord] Northwestern Univ, Evanston, IL 60208 USA.
[Perrier, Nancy] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
RP Hodin, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
OI Doherty, Gerard/0000-0002-1685-9552; Heller, Keith/0000-0003-2836-3359
NR 2
TC 12
Z9 12
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD AUG
PY 2012
VL 215
IS 2
BP 297
EP 297
DI 10.1016/j.jamcollsurg.2012.04.024
PG 1
WC Surgery
SC Surgery
GA 988PL
UT WOS:000307502900020
PM 22818100
ER
PT J
AU Feng, X
Scheinberg, P
Samsel, L
Rios, O
Chen, J
McCoy, JP
Ghanima, W
Bussel, JB
Young, NS
AF Feng, X.
Scheinberg, P.
Samsel, L.
Rios, O.
Chen, J.
McCoy, J. P., Jr.
Ghanima, W.
Bussel, J. B.
Young, N. S.
TI Decreased plasma cytokines are associated with low platelet counts in
aplastic anemia and immune thrombocytopenic purpura
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE aplastic anemia; cytokine; immune thrombocytopenic purpura
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EPIDERMAL-GROWTH-FACTOR; CD40 LIGAND;
T-CELLS; BONE-MARROW; THROMBOPOIETIN; EXPRESSION; CHEMOKINES; CD154
AB . Background: We previously found plasma levels of CD40 ligand (CD40L), chemokine (C-X-C motif) ligand 5 (CXCL5), chemokine (C-C motif) ligand 5 (CCL5) and epidermal growth factor (EGF) to be low in aplastic anemia (AA) patients and to be correlated with platelet count. Objectives: To study the association of CD40L, CXCL5, CCL5 and EGF with platelets. Methods: We measured cytokines in the plasma of immune thrombocytopenic purpura (ITP) and AA patients using the Luminex assay and confirmed the results in a mouse model and in vitro experiments. Results: Both ITP and AA showed similarly low levels of CD40L, CXCL5, CCL5 and EGF, compared with healthy controls. In ITP, levels of these proteins were significantly greater in patients with higher platelet counts than in those with lower platelet counts. In a murine thrombocytopenia model, levels of CD40L, CXCL5, CCL5 and EGF decreased with platelet count after immune-mediated destruction, while the cytokine levels increased when the platelet count recovered. In vitro, concentrations of these cytokines in the supernatants of platelet suspensions were proportional to platelet numbers, and levels in sera prepared by simple blood coagulation were equivalent to those in platelet-rich plasma-converted sera. mRNA expression for CXCL5, CCL5 and EGF was higher in platelets than in megakaryocytes, peripheral blood mononuclear cells, granulocytes and non-megakaryocytic bone marrow cells. Conclusions: Plasma CD40L, CXCL5, CCL5 and EGF are mainly platelet-derived, suggesting a role of platelets in immune responses and inflammation. Measurement of CD40L, CXCL5, CCL5 and EGF in human blood allowed testable inferences concerning physiology and pathophysiology in quantitative platelet disorders.
C1 [Feng, X.; Scheinberg, P.; Rios, O.; Chen, J.; Young, N. S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Samsel, L.; McCoy, J. P., Jr.] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
[Ghanima, W.] Ostfold Hosp Trust Fredrikstad, Dept Med, Fredrikstad, Norway.
[Bussel, J. B.] Cornell Univ, Weill Cornell Med Coll, Div Pediat Hematol Oncol, Platelet Disorders Ctr, New York, NY 10021 USA.
RP Feng, X (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Rm 3E-5216,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fengx2@nhlbi.nih.gov
RI Scheinberg, Phillip/H-5251-2012;
OI Scheinberg, Phillip/0000-0002-9047-4538
FU NIH; JBB; CCBF
FX This work was supported by the Intramural Research Program of the NIH,
JBB grants and CCBF.
NR 28
TC 14
Z9 15
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD AUG
PY 2012
VL 10
IS 8
BP 1616
EP 1623
DI 10.1111/j.1538-7836.2012.04757.x
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 989HW
UT WOS:000307551900021
PM 22537155
ER
PT J
AU Diaz-Ruiz, O
Zhang, YJ
Shan, LF
Malik, N
Hoffman, AF
Ladenheim, B
Cadet, JL
Lupica, CR
Tagliaferro, A
Brusco, A
Backman, CM
AF Diaz-Ruiz, Oscar
Zhang, YaJun
Shan, Lufei
Malik, Nasir
Hoffman, Alexander F.
Ladenheim, Bruce
Cadet, Jean Lud
Lupica, Carl R.
Tagliaferro, Adriana
Brusco, Alicia
Baeckman, Cristina M.
TI Attenuated response to methamphetamine sensitization and deficits in
motor learning and memory after selective deletion of beta-catenin in
dopamine neurons
SO LEARNING & MEMORY
LA English
DT Article
ID UNBIASED STEREOLOGICAL ESTIMATION; SYNAPTIC PLASTICITY; MOUSE MODEL;
CADHERIN; SKILL; CONSOLIDATION; MALFORMATION; HIPPOCAMPUS; STRENGTH;
RELEASE
AB In the present study, we analyzed mice with a targeted deletion of beta-catenin in DA neurons (DA-beta cat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-beta cat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine-induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-beta cat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-beta cat KO mice. This study demonstrates that ablation of beta-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that beta-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories.
C1 [Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Baeckman, Cristina M.] NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Hoffman, Alexander F.; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Ladenheim, Bruce; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Tagliaferro, Adriana; Brusco, Alicia] UBA CONICET, Inst Biol Celular & Neurociencias, RA-1120 Buenos Aires, DF, Argentina.
RP Backman, CM (reprint author), NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM cbackman@mail.nih.gov
RI Hoffman, Alexander/H-3035-2012; backman, cristina/C-1276-2013
OI Hoffman, Alexander/0000-0002-2676-0628;
FU U.S. Department of Health and Human Services; National Institutes of
Health; National Institute on Drug Abuse Intramural Research Program
FX This work was supported by the U.S. Department of Health and Human
Services, the National Institutes of Health, and the National Institute
on Drug Abuse Intramural Research Program. We thank Dr. Barry J. Hoffer
for helpful comments on the manuscript.
NR 42
TC 4
Z9 4
U1 0
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1072-0502
J9 LEARN MEMORY
JI Learn. Mem.
PD AUG
PY 2012
VL 19
IS 8
BP 341
EP 350
DI 10.1101/lm.026716.112
PG 10
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 991LV
UT WOS:000307703600006
PM 22822182
ER
PT J
AU Royo, C
Navarro, A
Clot, G
Salaverria, I
Gine, E
Jares, P
Colomer, D
Wiestner, A
Wilson, WH
Vegliante, MC
Fernandez, V
Hartmann, EM
Trim, N
Erber, WN
Swerdlow, SH
Klapper, W
Dyer, MJS
Vargas-Pabon, M
Ott, G
Rosenwald, A
Siebert, R
Lopez-Guillermo, A
Campo, E
Bea, S
AF Royo, C.
Navarro, A.
Clot, G.
Salaverria, I.
Gine, E.
Jares, P.
Colomer, D.
Wiestner, A.
Wilson, W. H.
Vegliante, M. C.
Fernandez, V.
Hartmann, E. M.
Trim, N.
Erber, W. N.
Swerdlow, S. H.
Klapper, W.
Dyer, M. J. S.
Vargas-Pabon, M.
Ott, G.
Rosenwald, A.
Siebert, R.
Lopez-Guillermo, A.
Campo, E.
Bea, S.
TI Non-nodal type of mantle cell lymphoma is a specific biological and
clinical subgroup of the disease
SO LEUKEMIA
LA English
DT Letter
ID GENE-EXPRESSION; GOOD PROGNOSIS; INVOLVEMENT; SUBSET
C1 [Royo, C.; Navarro, A.; Clot, G.; Salaverria, I.; Jares, P.; Colomer, D.; Vegliante, M. C.; Fernandez, V.; Campo, E.; Bea, S.] Univ Barcelona, Dept Pathol, Hematopathol Unit, Hosp Clin,IDIBAPS, Barcelona, Spain.
[Salaverria, I.; Siebert, R.] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Gine, E.; Lopez-Guillermo, A.] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
[Wiestner, A.; Wilson, W. H.] NIH, Hematol Branch, Bethesda, MD 20892 USA.
[Hartmann, E. M.; Rosenwald, A.] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany.
[Trim, N.] Addenbrookes Hosp, Cambridge, England.
[Erber, W. N.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Swerdlow, S. H.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Klapper, W.] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Pathol, Kiel, Germany.
[Dyer, M. J. S.] Univ Leicester, MRC Toxicol Unit, Leicester, Leics, England.
[Vargas-Pabon, M.] Hosp Jarrio, Asturias, Spain.
[Ott, G.] Robert Bosch Krankenhaus, Dept Pathol, Stuttgart, Germany.
[Ott, G.] Dr Margarete Fischer Inst Clin Pharmacol, Stuttgart, Germany.
RP Royo, C (reprint author), Univ Barcelona, Dept Pathol, Hematopathol Unit, Hosp Clin,IDIBAPS, Barcelona, Spain.
EM sbea@clinic.ub.es
RI Siebert, Reiner/A-8049-2010; Erber, Wendy/A-1955-2012; Navarro,
Alba/H-2611-2015; Royo, Cristina/H-3193-2015; SALAVERRIA,
ITZIAR/L-2246-2015; Klapper, Wolfram/S-6314-2016; Bea,
Silvia/K-7699-2014; Dyer, Martin/F-2691-2014
OI Campo, elias/0000-0001-9850-9793; Navarro, Alba/0000-0002-4041-0974;
Royo, Cristina/0000-0002-1214-4656; SALAVERRIA,
ITZIAR/0000-0002-2427-9822; Bea, Silvia/0000-0001-7192-2385; COLOMER,
DOLORS/0000-0001-7486-8484; Dyer, Martin/0000-0002-5033-2236
FU Intramural NIH HHS [ZIA HL005076-08]; NCATS NIH HHS [UL1 TR000005]; NCRR
NIH HHS [UL1 RR024153]
NR 15
TC 37
Z9 38
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD AUG
PY 2012
VL 26
IS 8
BP 1895
EP 1898
DI 10.1038/leu.2012.72
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 990RW
UT WOS:000307650000022
PM 22425896
ER
PT J
AU Fitzgerald, PJ
AF Fitzgerald, Paul J.
TI Whose side are you on: Does serotonin preferentially activate the right
hemisphere and norepinephrine the left?
SO MEDICAL HYPOTHESES
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; CEREBRAL GLUCOSE-METABOLISM;
AUDITORY-EVOKED POTENTIALS; HUMAN-BRAIN; INTERHEMISPHERIC ASYMMETRY;
H-3-IMIPRAMINE BINDING; REGIONAL-DISTRIBUTION; THERAPEUTIC RESPONSE;
TRYPTOPHAN DEPLETION; PSYCHIATRIC-ILLNESS
AB Serotonin (5-HT) and norepinephrine (NE) innervate both the left and right hemispheres of the brain, but whether they affect lateralization of function is unknown. This paper concisely examines evidence that these two neurotransmitters differentially affect the two hemispheres, and puts forth the novel hypothesis 5-HT preferentially activates the right hemisphere (RH) and NE the left hemisphere (LH). The principal lines of evidence comprise studies of: (1) 5-HT and NE level measurement, (2) receptor binding, (3) functional brain imaging, (4) dichotic listening, and (5) electroencephalography and evoked potentials. In assessing these 5 lines, emphasis is placed on studies of pharmaceutical drugs that affect the 5-HT and NE systems. While all of the data do not support the hypothesis, they are generally consistent with it, or a variant of the hypothesis that there is a bias toward 5-HT preferentially activating a majority of brain areas or functions in the RH, and NE a majority of LH areas or functions. If this hypothesis, or a variant of it, is correct, it may be relevant to understanding the physiological basis of neuropsychiatric disorders that could involve dysfunction in brain monoaminergic systems, as well as understanding potential lateralization of the effects of drugs that act on these systems. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Fitzgerald, Paul J.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
RP Fitzgerald, PJ (reprint author), NIAAA, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM pfitz@mbi.mb.jhu.edu
NR 54
TC 7
Z9 7
U1 0
U2 9
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD AUG
PY 2012
VL 79
IS 2
BP 250
EP 254
DI 10.1016/j.mehy.2012.05.001
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 978UG
UT WOS:000306770700032
PM 22647616
ER
PT J
AU Lu, RB
Chen, SL
Lee, SY
Chang, YH
Chen, SH
Chu, CH
Tzeng, NS
Lee, IH
Chen, PS
Yeh, TL
Huang, SY
Yang, YK
Hong, JS
AF Lu, Ru-Band
Chen, Shiou-Lan
Lee, Sheng-Yu
Chang, Yun-Hsuan
Chen, Shih-Heng
Chu, Chun-Hsieh
Tzeng, Nian-Sheng
Lee, I. Hui
Chen, Po See
Yeh, Tzung Lieh
Huang, San-Yuan
Yang, Yen Kuang
Hong, Jau-Shyong
TI Neuroprotective and neurogenesis agent for treating bipolar II disorder:
Add-on memantine to mood stabilizer works
SO MEDICAL HYPOTHESES
LA English
DT Letter
ID NEUROTROPHIC FACTOR LEVELS; MESSENGER-RNA EXPRESSION;
DOPAMINERGIC-NEURONS; CHOLINERGIC NEURONS; CLINICAL SPECTRUM; PLACE
PREFERENCE; NMDA-GLUTAMATE; BRAIN; BDNF; DEPRESSION
AB Bipolar disorder, characterized by a dysregulation of mood, impulsivity, risky behavior and interpersonal problems, is a recurrent and often becomes chronic psychiatric illness. However, bipolar subtypes are not often recognized in psychiatric settings, especially bipolar II subtype, until Akiskal and Angst made clear definition to bipolar I (BP-I) and bipolar II (BP-II) disorder in 1999. More and more studies, not only on family inheritance, diagnosis, but also on disease process have been reported that BP-I and BP-II are two different disorders with distinct pathological mechanisms. In general, patients with BP-II express less symptoms and have shorter hypomania stages than BP-I. According to a longitudinal research, patients with BP-II have poor recovery than do BP-I patients.
Memantine used to be recognized as a noncompetitive N-methyl-D-aspartate receptor antagonist. However, it was found to have neuroprotective and neurogenesis effect in several neurodegenerative diseases in the past years. We found that memantine could inhibit brain inflammatory response through its action on neuroglial cells and provide neurotrophic effect. The above evidences of benefit on autoimmune system with memantine would support that memantine as add-on therapy to valproate might be more effective than valproate alone on improvement of the neuron degeneration in bipolar disorders. Review articles indicate that not only the mood stabilizers provide with good neuroprotection, but the memantine also have conspicuous anti-autoimmune and neurogenesis effect. Therefore, we propose that drugs with neuroprotective effect and neurotrophic effect may treat neurodegenerative diseases including BP-II. The combination treatment of mood stabilizers memantine may not only augment and improve the remedy for bipolar disorders, but also repair the damaged neurons and neurogenesis through activation of astroglial cell and release of neurotrophic factors. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Dept Psychiat, Inst Behav Med, Tainan 70428, Taiwan.
[Lu, Ru-Band; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsieh; Yeh, Tzung Lieh; Yang, Yen Kuang] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan.
[Lu, Ru-Band; Chang, Yun-Hsuan] Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Div Clin Psychol, Tainan 70428, Taiwan.
[Huang, San-Yuan] Triservice Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan.
[Tzeng, Nian-Sheng; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med & Hosp, Dept Psychiat, Inst Behav Med, 138 Sheng Li Rd, Tainan 70428, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Intramural NIH HHS [ZIA ES090082-15]
NR 62
TC 3
Z9 4
U1 0
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD AUG
PY 2012
VL 79
IS 2
BP 280
EP 283
DI 10.1016/j.mehy.2012.04.042
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 978UG
UT WOS:000306770700042
PM 22677298
ER
PT J
AU Feldman, D
Roniger, M
Bar-Sinai, A
Braitbard, O
Natan, C
Love, DC
Hanover, JA
Hochman, J
AF Feldman, Dafna
Roniger, Maayan
Bar-Sinai, Allan
Braitbard, Ori
Natan, Carmit
Love, Dona C.
Hanover, John A.
Hochman, Jacob
TI The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein
Tumor Modulator
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID RIBOSOMAL-PROTEIN L5; HUMAN BREAST-CANCER; T-CELL LYMPHOMAS; NUCLEOLAR
LOCALIZATION; NUCLEAR EXPORT; NUCLEOPHOSMIN; MMTV; GENE; INHIBITION;
CARCINOMA
AB Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator. Mol Cancer Res; 10(8); 1077-86. (C) 2012 AACR.
C1 [Feldman, Dafna; Roniger, Maayan; Bar-Sinai, Allan; Braitbard, Ori; Natan, Carmit; Hochman, Jacob] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Dev Biol, IL-91904 Jerusalem, Israel.
[Love, Dona C.; Hanover, John A.] NIDDK, LCBB, NIH, Bethesda, MD USA.
RP Hochman, J (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Dev Biol, Edmond Safra Campus, IL-91904 Jerusalem, Israel.
EM hochman@vms.huji.ac.il
FU Israel Science Foundation [ISF 1308-04]
FX This work was supported in part by the Israel Science Foundation: ISF
1308-04 (to J. Hochman).
NR 50
TC 5
Z9 6
U1 2
U2 10
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 AUG
PY 2012
VL 10
IS 8
BP 1077
EP 1086
DI 10.1158/1541-7786.MCR-11-0581
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 995QX
UT WOS:000308028200008
PM 22740636
ER
PT J
AU Avan, A
Crea, F
Paolicchi, E
Funel, N
Galvani, E
Marquez, VE
Honeywell, RJ
Danesi, R
Peters, GJ
Giovannetti, E
AF Avan, Amir
Crea, Francesco
Paolicchi, Elisa
Funel, Niccola
Galvani, Elena
Marquez, Victor E.
Honeywell, Richard J.
Danesi, Romano
Peters, Godefridus J.
Giovannetti, Elisa
TI Molecular Mechanisms Involved in the Synergistic Interaction of the EZH2
Inhibitor 3-Deazaneplanocin A with Gemcitabine in Pancreatic Cancer
Cells
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID GROUP PROTEIN EZH2; ZESTE HOMOLOG 2; PROSTATE-CANCER; LUNG-CANCER;
PHARMACOLOGICAL DISRUPTION; DUCTAL ADENOCARCINOMA; DNA METHYLATION;
CARCINOMA-CELLS; TUMOR-GROWTH; STEM-CELLS
AB Pancreatic ductal adenocarcinoma (PDAC) is characterized by overexpression of enhancer of Zeste homolog-2 (EZH2), which plays a pivotal role in cancer stem cell (CSC) self-renewal through methylation of histone H3 lysine-27 (H3K27me3). Against this background, EZH2 was identified as an attractive target, and we investigated the interaction of the EZH2 inhibitor DZNeP with gemcitabine. EZH2 expression was detected by quantitative PCR in 15 PDAC cells, including seven primary cell cultures, showing that expression values correlated with their originator tumors (Spearman R-2 = 0.89, P = 0.01). EZH2 expression in cancer cells was significantly higher than in normal ductal pancreatic cells and fibroblasts. The 3-deazaneplanocin A (DZNeP; 5 mu mol/L, 72-hour exposure) modulated EZH2 and H3K27me3 protein expression and synergistically enhanced the antiproliferative activity of gemcitabine, with combination index values of 0.2 (PANC-1), 0.3 (MIA-PaCa-2), and 0.7 (LPC006). The drug combination reduced the percentages of cells in G2-M phase (e.g., from 27% to 19% in PANC-1, P < 0.05) and significantly increased apoptosis compared with gemcitabine alone. Moreover, DZNeP enhanced the mRNA and protein expression of the nucleoside transporters hENT1/hCNT1, possibly because of the significant reduction of deoxynucleotide content (e.g., 25% reduction of deoxycytidine nucleotides in PANC-1), as detected by liquid chromatography/tandem mass spectrometry. DZNeP decreased cell migration, which was additionally reduced by DZNeP/gemcitabine combination (-20% in LPC006, after 8-hour exposure, P < 0.05) and associated with increased E-cadherin mRNA and protein expression. Furthermore, DZNeP and DZNeP/gemcitabine combination significantly reduced the volume of PDAC spheroids growing in CSC-selective medium and decreased the proportion of CD133+ cells. All these molecular mechanisms underlying the synergism of DZNeP/gemcitabine combination support further studies on this novel therapeutic approach for treatment of PDACs. Mol Cancer Ther; 11(8); 1735-46. (C) 2012 AACR.
C1 [Giovannetti, Elisa] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands.
[Crea, Francesco; Paolicchi, Elisa; Danesi, Romano] Univ Pisa, Dept Internal Med, Pisa, Italy.
[Funel, Niccola] Univ Pisa, Dept Surg, Pisa, Italy.
[Marquez, Victor E.] NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
RP Giovannetti, E (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, CCA Room 1-52,Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM e.giovannetti@vumc.nl
RI Crea, Francesco /I-8383-2015; Galvani, Elena/L-3133-2016;
OI Crea, Francesco/0000-0002-4903-2973; Giovannetti,
Elisa/0000-0002-7565-7504; Paolicchi, Elisa/0000-0001-6101-7576
FU Netherlands-Organization for Scientific Research [91611046]; AIRC-Marie
Curie (International Fellowship); Iran's National-Elites-Foundation;
CCA-VICI foundation [2012-5-07]; NIH, NCI, Center for Cancer Research
FX This work was supported by grants from the Netherlands-Organization for
Scientific Research (Veni grant #91611046 to E. Giovannetti), AIRC-Marie
Curie (International Fellowship to E. Giovannetti), Iran's
National-Elites-Foundation (A. Avan), and CCA-VICI foundation (grant
#2012-5-07 to A. Avan, G.J. Peters, and E. Giovannetti); and by the
Intramural Research Program of the NIH, NCI, Center for Cancer Research
(to V.E. Marquez).
NR 49
TC 32
Z9 32
U1 1
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD AUG
PY 2012
VL 11
IS 8
BP 1735
EP 1746
DI 10.1158/1535-7163.MCT-12-0037
PG 12
WC Oncology
SC Oncology
GA 995PG
UT WOS:000308022100013
PM 22622284
ER
PT J
AU Malkesman, O
Austin, DR
Tragon, T
Henter, ID
Reed, JC
Pellecchia, M
Chen, G
Manji, HK
AF Malkesman, O.
Austin, D. R.
Tragon, T.
Henter, I. D.
Reed, J. C.
Pellecchia, M.
Chen, G.
Manji, H. K.
TI Targeting the BH3-interacting domain death agonist to develop
mechanistically unique antidepressants
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE AIF; behavior; Bcl-2; Bid; depression; stress
ID NEURONAL CELL-DEATH; APOPTOSIS-INDUCING FACTOR; FOCAL CEREBRAL-ISCHEMIA;
TAIL SUSPENSION TEST; FORCED SWIM TEST; ANIMAL-MODELS; BCL-2 FAMILY;
LEARNED HELPLESSNESS; MOOD DISORDERS; DEPRESSION
AB The BH3-interacting domain death agonist (Bid) is a pro-apoptotic member of the B-cell lymphoma-2 (Bcl-2) protein family. Previous studies have shown that stress reduces levels of Bcl-2 in brain regions implicated in the pathophysiology of mood disorders, whereas antidepressants and mood stabilizers increase Bcl-2 levels. The Bcl-2 protein family has an essential role in cellular resilience as well as synaptic and neuronal plasticity and may influence mood and affective behaviors. This study inhibited Bid in mice using two pharmacological antagonists (BI-11A7 and BI-2A7); the selective serotonin reuptake inhibitor citalopram was used as a positive control. These agents were studied in several well-known rodent models of depression-the forced swim test (FST), the tail suspension test (TST), and the learned helplessness (LH) paradigm-as well as in the female urine sniffing test (FUST), a measure of sex-related reward-seeking behavior. Citalopram and BI-11A7 both significantly reduced immobility time in the FST and TST and attenuated escape latencies in mice that underwent the LH paradigm. In the FUST, both agents significantly improved duration of female urine sniffing in mice that had developed helplessness. LH induction increased the activation of apoptosis-inducing factor (AIF), a caspase-independent cell death constituent activated by Bid, and mitochondrial AIF expression was attenuated by chronic BI-11A7 infusion. Taken together, the results suggest that functional perturbation of apoptotic proteins such as Bid and, alternatively, enhancement of Bcl-2 function, is a putative strategy for developing novel therapeutics for mood disorders. Molecular Psychiatry (2012) 17, 770-780; doi:10.1038/mp.2011.77; published online 5 July 2011
C1 [Chen, G.; Manji, H. K.] Johnson & Johnson Pharmaceut Res & Dev, LLC, Titusville, NJ 08560 USA.
[Malkesman, O.; Austin, D. R.; Tragon, T.; Chen, G.; Manji, H. K.] NIMH, Mol Pathophysiol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Malkesman, O.; Austin, D. R.; Tragon, T.; Henter, I. D.; Chen, G.; Manji, H. K.] NIMH, Mood & Anxiety Disorders Res Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Reed, J. C.; Pellecchia, M.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
RP Manji, HK (reprint author), Johnson & Johnson Pharmaceut Res & Dev, LLC, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 USA.
EM Hmanji@its.jnj.com
RI Chen, Guang/A-2570-2017
FU Intramural Research Program of the National Institute of Mental Health
(NIMH); NIH [R01 HL082574]
FX We would like to acknowledge the support of the Intramural Research
Program of the National Institute of Mental Health (NIMH: OM, TT, DRA,
IDH, GC and HKM) and NIH Grant (R01 HL082574) to JCR. Adithya Simha
provided invaluable technical assistance.
NR 72
TC 11
Z9 11
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2012
VL 17
IS 8
BP 770
EP 780
DI 10.1038/mp.2011.77
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 978QP
UT WOS:000306760600002
PM 21727899
ER
PT J
AU Badner, JA
Koller, D
Foroud, T
Edenberg, H
Nurnberger, JI
Zandi, PP
Willour, VL
McMahon, FJ
Potash, JB
Hamshere, M
Grozeva, D
Green, E
Kirov, G
Jones, I
Jones, L
Craddock, N
Morris, D
Segurado, R
Gill, M
Sadovnick, D
Remick, R
Keck, P
Kelsoe, J
Ayub, M
MacLean, A
Blackwood, D
Liu, CY
Gershon, ES
McMahon, W
Lyon, GJ
Robinson, R
Ross, J
Byerley, W
AF Badner, J. A.
Koller, D.
Foroud, T.
Edenberg, H.
Nurnberger, J. I., Jr.
Zandi, P. P.
Willour, V. L.
McMahon, F. J.
Potash, J. B.
Hamshere, M.
Grozeva, D.
Green, E.
Kirov, G.
Jones, I.
Jones, L.
Craddock, N.
Morris, D.
Segurado, R.
Gill, M.
Sadovnick, D.
Remick, R.
Keck, P.
Kelsoe, J.
Ayub, M.
MacLean, A.
Blackwood, D.
Liu, C-Y
Gershon, E. S.
McMahon, W.
Lyon, G. J.
Robinson, R.
Ross, J.
Byerley, W.
TI Genome-wide linkage analysis of 972 bipolar pedigrees using
single-nucleotide polymorphisms
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE bipolar disorder; genome-wide linkage analysis; single-nucleotide
polymorphisms
ID DISORDER SUSCEPTIBILITY LOCUS; ORDERED SUBSET ANALYSIS; COMPLEX TRAITS;
ASSOCIATION; SCAN; INDIVIDUALS; FAMILIES; GENES; CHROMOSOME-22;
POPULATION
AB Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the similar to 1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing. Molecular Psychiatry (2012) 17, 818-826; doi:10.1038/mp.2011.89; published online 19 July 2011
C1 [Ross, J.; Byerley, W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Badner, J. A.; Liu, C-Y; Gershon, E. S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Koller, D.; Foroud, T.; Edenberg, H.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Edenberg, H.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA.
[Nurnberger, J. I., Jr.] Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA.
[Zandi, P. P.; Willour, V. L.; Potash, J. B.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Zandi, P. P.; Willour, V. L.; Potash, J. B.] Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Zandi, P. P.] Johns Hopkins Univ, Sch Med, Dept Mental Hlth, Baltimore, MD USA.
[McMahon, F. J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Hamshere, M.; Grozeva, D.; Green, E.; Kirov, G.; Jones, L.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Cardiff, Wales.
[Morris, D.; Segurado, R.; Gill, M.] Trinity Coll Dublin, Dublin, Ireland.
[Jones, L.] Univ Birmingham, Birmingham, W Midlands, England.
[Sadovnick, D.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada.
[Remick, R.] St Pauls Hosp, Dept Psychiat, Vancouver, BC V6Z 1Y6, Canada.
[Keck, P.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA.
[Kelsoe, J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Ayub, M.] Univ Durham, Sch Med & Hlth, Durham, England.
[MacLean, A.; Blackwood, D.] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland.
[McMahon, W.; Lyon, G. J.; Robinson, R.] Univ Utah, Med Ctr, Dept Psychiat, Salt Lake City, UT USA.
[Byerley, W.] Vet Affairs Med Ctr, San Francisco Dept, San Francisco, CA 94121 USA.
RP Byerley, W (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM jbadner@yoda.bsd.uchicago.edu; william.byerley@ucsf.edu
RI Liu, Chunyu/G-7561-2012; Lyon, Gholson/D-2765-2014; Segurado,
Ricardo/K-6116-2014;
OI Edenberg, Howard/0000-0003-0344-9690; Liu, Chunyu/0000-0002-5986-4415;
Lyon, Gholson/0000-0002-5869-0716; Segurado,
Ricardo/0000-0002-3547-6733; McMahon, Francis/0000-0002-9469-305X;
Morris, Derek/0000-0002-3413-570X; Nurnberger, John/0000-0002-7674-1767;
Gill, Michael/0000-0003-0206-5337
FU National Institutes of Health (NIH/NIMH) [R01-MH077314]; Wellcome Trust
[045267/Z/WRE/MB/JAT]
FX This work was supported by National Institutes of Health (NIH/NIMH)
research Grant R01-MH077314 (JAB, WB). Wellcome Trust
045267/Z/WRE/MB/JAT (MG, RS).
NR 47
TC 13
Z9 13
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2012
VL 17
IS 8
BP 818
EP 826
DI 10.1038/mp.2011.89
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 978QP
UT WOS:000306760600006
PM 21769101
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, D.
Volkow, N. D.
TI Resting functional connectivity of language networks: characterization
and reproducibility
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE connectivity; fMRI; gender; laterality; modularity; speech
ID HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; SEX-DIFFERENCES; COMPREHENSION;
ASYMMETRIES; VARIANTS; BEHAVIOR; NUCLEUS; ANATOMY; GENDER
AB The neural basis of language comprehension and production has been associated with superior temporal (Wernicke's) and inferior frontal (Broca's) cortical areas, respectively. However, recent resting-state functional connectivity (RSFC) and lesion studies have implicated a more extended network in language processing. Using a large RSFC data set from 970 healthy subjects and seed regions in Broca's and Wernicke's, we recapitulate this extended network that includes not only adjoining prefrontal, temporal and parietal regions but also bilateral caudate and left putamen/globus pallidus and subthalamic nucleus. We also show that the language network has predominance of short-range functional connectivity (except posterior Wernicke's area that exhibited predominant long-range connectivity), which is consistent with reliance on local processing. Predominantly, long-range connectivity was left lateralized (except anterior Wernicke's area that exhibited rightward lateralization). The language network also exhibited anti-correlated activity with auditory (only for Wernicke's area) and visual cortices that suggests integrated sequential activity with regions involved with listening or reading words. Assessment of the intra-subject's reproducibility of this network and its characterization in individuals with language dysfunction is required to determine its potential as a biomarker for language disorders. Molecular Psychiatry (2012) 17, 841-854; doi:10.1038/mp.2011.177; published online 3 January 2012
C1 [Tomasi, D.; Volkow, N. D.] Brookhaven Natl Lab, Dept Med, Lab Neuroimaging LNI NIAAA, NIAAA, Upton, NY 11973 USA.
[Volkow, N. D.] NIDA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Dept Med, Lab Neuroimaging LNI NIAAA, NIAAA, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX We are very grateful to Olaf Sporns for assistance during computation of
the modularity of the language network with the Brain Connectivity
Toolbox. This study was accomplished with support from the National
Institutes of Alcohol Abuse and Alcoholism (2RO1AA09481).
NR 66
TC 62
Z9 64
U1 7
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2012
VL 17
IS 8
BP 841
EP 854
DI 10.1038/mp.2011.177
PG 14
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 978QP
UT WOS:000306760600008
PM 22212597
ER
PT J
AU Kim, YS
Kang, HS
Takeda, Y
Hom, L
Song, HY
Jensen, J
Jetten, AM
AF Kim, Yong-Sik
Kang, Hong Soon
Takeda, Yukimasa
Hom, Lisa
Song, Ho-Yeon
Jensen, Jan
Jetten, Anton M.
TI Glis3 regulates neurogenin 3 expression in pancreatic beta-cells and
interacts with its activator, Hnf6
SO MOLECULES AND CELLS
LA English
DT Article
DE Glis3; Glis3 binding site; Hnf6; Ngn3
ID HEPATOCYTE NUCLEAR FACTOR-6; ZINC-FINGER PROTEIN; NEONATAL
DIABETES-MELLITUS; TRANSCRIPTION FACTOR; REPRESSOR FUNCTIONS;
TRANSACTIVATION; DIFFERENTIATION; HOMEODOMAIN; PROGENITORS; NETWORK
AB The Kruppel-like zinc finger transcription factor, Glis3, has been associated with neonatal diabetes in humans and mice, and implicated in the regulation of pancreatic beta-cell generation. However, its precise function in the development of pancreatic beta-cells has not yet been elucidated. In this study, we provide evidence that Glis3 regulates Neurogenin 3 (Ngn3) through its distal promoter region. Previous studies showed that the distal region and proximal region of Ngn3 promoter contains various transcription binding sites, including binding sites for pancreatic and duodenal homeobox 1 (Pdx1), Hnf1 beta and Hnf6. Interestingly, putative Glis3 binding sites (Glis3BS) were found in the distal region of Ngn3 promoter close to the Hnf6 binding sites. This suggested that along with Hnf6, Glis3 may also be involved in the regulation of Ngn3 expression. This hypothesis is supported by data showing that Glis3 can bind to the Ngn3 promoter directly and activate Ngn3 transcriptional activity. Additionally, Glis3 can interact directly with Hnf6 in vitro and in vivo. The amino-terminus in Glis3 and the homeodomain of Hnf6 are critical for this interaction. These data suggest that crosstalk between Glis3 and Hnf6 may play an important role in the regulation of Ngn3 during pancreatic endocrine progenitor cell specification and development.
C1 [Kim, Yong-Sik; Song, Ho-Yeon] Soonchunhyang Univ, Coll Med, Dept Microbiol, Cheonan 314864, South Korea.
[Kim, Yong-Sik; Kang, Hong Soon; Takeda, Yukimasa; Jetten, Anton M.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
[Kim, Yong-Sik; Hom, Lisa; Jensen, Jan] Cleveland Clin, Diabet Program, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, Cleveland, OH 44195 USA.
RP Kim, YS (reprint author), Soonchunhyang Univ, Coll Med, Dept Microbiol, Cheonan 314864, South Korea.
EM yongsikkim@sch.ac.kr; jensen@ccf.org; jetten@niehs.nih.gov
OI Jensen, Jan/0000-0003-0657-4032; Jetten, Anton/0000-0003-0954-4445
FU NIEHS, NIH [Z01-ES-100485]
FX Authors specially thank Dr. M. German (UCSF) and Dr. F. Lemaigre
(Universite Catholique de Louvain) for the human Ngn3 promoter and Hnf6
constructs, respectively. Authors also thank to Dr. M. Schmerr
(Cleveland Clinic), Kristin Lichti-Kaiser, and Gary Zeruth (NIEHS) for
their critical review and comments. This research was supported by the
Intramural Research Program of the NIEHS, NIH (Z01-ES-100485).
NR 32
TC 10
Z9 11
U1 0
U2 7
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
J9 MOL CELLS
JI Mol. Cells
PD AUG
PY 2012
VL 34
IS 2
BP 193
EP 200
DI 10.1007/s10059-012-0109-z
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 992HY
UT WOS:000307767400012
PM 22820919
ER
PT J
AU Tasca, G
Odgerel, Z
Monforte, M
Aurino, S
Clarke, NF
Waddell, LB
Udd, B
Ricci, E
Goldfarb, LG
AF Tasca, Giorgio
Odgerel, Zagaa
Monforte, Mauro
Aurino, Stefania
Clarke, Nigel F.
Waddell, Leigh B.
Udd, Bjarne
Ricci, Enzo
Goldfarb, Lev G.
TI NOVEL FLNC MUTATION IN A PATIENT WITH MYOFIBRILLAR MYOPATHY IN
COMBINATION WITH LATE-ONSET CEREBELLAR ATAXIA
SO MUSCLE & NERVE
LA English
DT Article
ID FILAMIN-C; DISTAL MYOPATHY; CAP DISEASE; GENE; DELETION; PROTEIN; DOMAIN
AB Introduction: Mutations in the gene that encodes filamin C, FLNC, represent a rare cause of a distinctive type of myofibrillar myopathy (MFM). Methods: We investigated an Italian patient by means of muscle biopsy, muscle and brain imaging and molecular analysis of MFM genes. Results: The patient harbored a novel 7256C>T, p.Thr2419Met mutation in exon 44 of FLNC. Clinical, pathological and muscle MRI findings were similar to the previously described filaminopathy cases. This patient had, in addition, cerebellar ataxia with atrophy of cerebellum and vermis evident on brain MRI scan. Extensive screening failed to establish a cause of cerebellar atrophy. Conclusions: We report an Italian filaminopathy patient, with a novel mutation in a highly conserved region. This case raises the possibility that the disease spectrum caused by FLNC may include cerebellar dysfunction. Muscle Nerve 46: 275-282, 2012
C1 [Odgerel, Zagaa; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Monforte, Mauro; Ricci, Enzo] Catholic Univ, Sch Med, Inst Neurol, Rome, Italy.
[Aurino, Stefania] Univ Naples 2, Dipartimento Patol Gen, Naples, Italy.
[Clarke, Nigel F.; Waddell, Leigh B.] Univ Sydney, Discipline Pediat & Child Hlth, Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2006, Australia.
[Udd, Bjarne] Univ Tampere, Tampere Univ Hosp, Dept Neurol, Neuromuscular Res Ctr, Tampere 33520, Finland.
EM tasca.giorgio@virgilio.it
OI Monforte, Mauro/0000-0002-4327-6969; RICCI, Enzo/0000-0003-3092-3597;
Tasca, Giorgio/0000-0003-0849-9144
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Institute of Neurological Disorders and Stroke, National
Institutes of Health. We want to thank the patient and his family for
participation to the study and Manuela Papacci for technical assistance.
We thank Dr Nigel Laing, University of Western Australia, for analysis
of exons 30-40 of MYH7.
NR 28
TC 8
Z9 8
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD AUG
PY 2012
VL 46
IS 2
BP 275
EP 282
DI 10.1002/mus.23349
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 975AH
UT WOS:000306478400018
PM 22806379
ER
PT J
AU Gopalakrishnan, J
Chim, YCF
Ha, A
Basiri, ML
Lerit, DA
Rusan, NM
Avidor-Reiss, T
AF Gopalakrishnan, Jayachandran
Chim, Yiu-Cheung Frederick
Ha, Andrew
Basiri, Marcus L.
Lerit, Dorothy A.
Rusan, Nasser M.
Avidor-Reiss, Tomer
TI Tubulin nucleotide status controls Sas-4-dependent pericentriolar
material recruitment
SO NATURE CELL BIOLOGY
LA English
DT Article
ID CELL-CYCLE; MICROTUBULE NUCLEATION; DROSOPHILA NEUROBLASTS; CENTRIOLE
DUPLICATION; CENTROSOME SIZE; C-ELEGANS; PROTEIN; SAS-4; CPAP;
POLYMERIZATION
AB Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity(1). Centrosomes consist of a centriole pair surrounded by protein network known as pericentriolar material(1) (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes(2-4). Here, we report a role for tubulin in regulating PCM recruitment through the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins(5,6). A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These results suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, the regulation of PCM recruitment by tubulin depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules(7). On the basis of its guanine-bound state, tubulin can act as a molecular switch in PCM recruitment.
C1 [Gopalakrishnan, Jayachandran; Chim, Yiu-Cheung Frederick; Ha, Andrew; Basiri, Marcus L.; Avidor-Reiss, Tomer] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Lerit, Dorothy A.; Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Avidor-Reiss, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM tomer_avidor-reiss@hms.harvard.edu
RI Rusan, Nasser/P-3511-2016
FU National Institute of General Medical Sciences [R01GM098394]
FX We would like to thank J. Iwasa for scientific illustrations; T.
Mitchision A. Johnson, I. Cheeseman and J. Malicki for scientific
discussions; T. Kaufman, J. Raff, B. Raynaud-Messina and T. K. Tang
(Institute of Biomedical Sciences, Taipei, Taiwan) for reagents; R. Reed
laboratory (Harvard Medical School, USA), F. Eric, A. Hari, R. Rodriguez
for technical help with biophysical experiments; E. Koundakjian for
scientific editing and discussions; and electron microscopy facility
staff at HMS for help with electron microscopy analyses. This work was
supported by a grant (R01GM098394) from the National Institute of
General Medical Sciences.
NR 40
TC 24
Z9 24
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD AUG
PY 2012
VL 14
IS 8
BP 865
EP U197
DI 10.1038/ncb2527
PG 17
WC Cell Biology
SC Cell Biology
GA 983JP
UT WOS:000307115900016
PM 22729084
ER
PT J
AU Lee, I
Yoon, KY
Kang, CM
Lin, X
Chen, XY
Kim, JY
Kim, SM
Ryu, EK
Choe, YS
AF Lee, Iljung
Yoon, Kwang Yup
Kang, Choong Mo
Lin, Xin
Chen, Xiaoyuan
Kim, Jung Young
Kim, Sung-Min
Ryu, Eun Kyoung
Choe, Yearn Seong
TI Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3
tumor-bearing mice using Cu-64-DOTA-VEGF(121) and microPET
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE KR-31831; Cu-64-DOTA-VEGF(121); MicroPET; VEGFR2; Angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; FACTOR VEGF;
OVARIAN-CARCINOMA; IN-VIVO; RECEPTOR; EXPRESSION; KDR; PET; METABOLISM
AB KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with Cu-64-DOTA-VEGF(121). KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups. After injections occurred daily for 28 days, all groups of mice underwent post-treatment microPET imaging after injection with Cu-64-DOTA-VEGF(121). The post-treatment images showed high tumor uptake in the control group and reduced tumor uptake in both the blocking and treatment groups. ROI analysis of the tumor images revealed 6.25%+/-1.18% ID/g at 1 h, 6.55%+/-0.69% ID/g at 2 h, and 4.68%+/-0.63% ID/g at 16 h ill the control group; 3.87%+/-0.45% ID/g at 1 h, 4.50%+/-0.44% ID/g at 2 h, and 3.63%+/-0.25% ID/g at 16 h in the blocking group; and 4.03%+/-0.74% ID/g at 1 h, 4.37%+/-0.67% ID/g at 2 h, and 3.83%+/-0.90% ID/g at 16 h in the treatment group. Biodistribution obtained after the post-treatment microPET imaging also demonstrated high tumor uptake (3.74%+/-0.27% ID/g) in the control group and reduced uptakes in both the blocking group (2.69%+/-0.73% ID/g, P<.05) and the treatment group (3.11%+/-0.25% ID/g, P<.05), which correlated well with microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2 and CD31 expressions in tumor tissues of the control and blocking groups than in tumor tissues of the treatment group. These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Lee, Iljung; Yoon, Kwang Yup; Kang, Choong Mo; Choe, Yearn Seong] Sungkyunkwan Univ, Dept Nucl Med, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea.
[Lin, Xin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Kim, Jung Young] Korea Inst Radiol & Med Sci, Mol Imaging Res Ctr, Seoul 139706, South Korea.
[Kim, Sung-Min; Ryu, Eun Kyoung] Korea Basic Sci Inst, Div Magnet Resonance Res, Chungbuk 363883, South Korea.
RP Choe, YS (reprint author), Sungkyunkwan Univ, Dept Nucl Med, Samsung Med Ctr, Sch Med, 50 Ilwon Dong, Seoul 135710, South Korea.
EM ysnm.choe@samsung.com
FU National Research Foundation of Korea (NRF); Korea government (MEST)
[2011-0027525]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (No. 2011-0027525). We
thank Drs. Kyu Yang Yi and Sung-Eun Yoo at the Korea Research Institute
of Chemical Technology (KRICT) for the generous gift of KR-31831 and
Molecular Imaging Research Center of the KIRAMS for the supply of
64Cu. We also thank Mr. Hunnyun Kim for assistance with
microPET imaging.
NR 26
TC 4
Z9 4
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD AUG
PY 2012
VL 39
IS 6
BP 840
EP 846
DI 10.1016/j.nucmedbio.2012.01.007
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 982KD
UT WOS:000307041000013
PM 22406249
ER
PT J
AU Salpea, P
Russanova, VR
Hirai, TH
Sourlingas, TG
Sekeri-Pataryas, KE
Romero, R
Epstein, J
Howard, BH
AF Salpea, Paraskevi
Russanova, Valya R.
Hirai, Tazuko H.
Sourlingas, Thomae G.
Sekeri-Pataryas, Kalliope E.
Romero, Roberto
Epstein, Jonathan
Howard, Bruce H.
TI Postnatal development- and age-related changes in DNA-methylation
patterns in the human genome
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID INTERINDIVIDUAL EPIGENETIC VARIATION; PERIPHERAL-BLOOD MONOCYTES;
STEM-CELLS; DENDRITIC CELLS; GENE FAMILIES; CYTOSINE METHYLATION;
PROMOTER DNA; CPG ISLANDS; CANCER; DIFFERENTIATION
AB Alterations in DNA methylation have been reported to occur during development and aging; however, much remains to be learned regarding post-natal and age-associated epigenome dynamics, and few if any investigations have compared human methylome patterns on a whole genome basis in cells from newborns and adults. The aim of this study was to reveal genomic regions with distinct structure and sequence characteristics that render them subject to dynamic post-natal developmental remodeling or age-related dysregulation of epigenome structure. DNA samples derived from peripheral blood monocytes and in vitro differentiated dendritic cells were analyzed by methylated DNA Immunoprecipitation (MeDIP) or, for selected loci, bisulfite modification, followed by next generation sequencing. Regions of interest that emerged from the analysis included tandem or interspersed-tandem gene sequence repeats (PCDHG, FAM90A, HRNR, ECEL1P2), and genes with strong homology to other family members elsewhere in the genome (FZD1, FZD7 and FGF17). Our results raise the possibility that selected gene sequences with highly homologous copies may serve to facilitate, perhaps even provide a clock-like function for, developmental and age-related epigenome remodeling. If so, this would represent a fundamental feature of genome architecture in higher eukaryotic organisms.
C1 [Salpea, Paraskevi; Russanova, Valya R.; Hirai, Tazuko H.; Howard, Bruce H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Sourlingas, Thomae G.; Sekeri-Pataryas, Kalliope E.] Natl Ctr Sci Res Demokritos, Inst Biol, Aghia Paraskevi 15310, Attikis, Greece.
[Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
[Epstein, Jonathan] NICHHD, Mol Genom Lab, NIH, Bethesda, MD 20892 USA.
RP Howard, BH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM howard@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health
(National Institute of Child Health and Human Development)
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health (National Institute of Child Health and
Human Development).
NR 95
TC 19
Z9 20
U1 3
U2 12
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 AUG
PY 2012
VL 40
IS 14
BP 6477
EP 6494
DI 10.1093/nar/gks312
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 988QD
UT WOS:000307504700017
PM 22495928
ER
PT J
AU Singh, DK
Popuri, V
Kulikowicz, T
Shevelev, I
Ghosh, AK
Ramamoorthy, M
Rossi, ML
Janscak, P
Croteau, DL
Bohr, VA
AF Singh, Dharmendra Kumar
Popuri, Venkateswarlu
Kulikowicz, Tomasz
Shevelev, Igor
Ghosh, Avik K.
Ramamoorthy, Mahesh
Rossi, Marie L.
Janscak, Pavel
Croteau, Deborah L.
Bohr, Vilhelm A.
TI The human RecQ helicases BLM and RECQL4 cooperate to preserve genome
stability
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ROTHMUND-THOMSON-SYNDROME; SYNDROME GENE-PRODUCT; SISTER-CHROMATID
EXCHANGES; BLOOMS-SYNDROME HELICASE; DNA-REPLICATION; HOLLIDAY
JUNCTIONS; HUMAN RECQ5-BETA; SYNDROME PROTEIN; POLYMERASE-II; G4 DNA
AB Bacteria and yeast possess one RecQ helicase homolog whereas humans contain five RecQ helicases, all of which are important in preserving genome stability. Three of these, BLM, WRN and RECQL4, are mutated in human diseases manifesting in premature aging and cancer. We are interested in determining to which extent these RecQ helicases function cooperatively. Here, we report a novel physical and functional interaction between BLM and RECQL4. Both BLM and RECQL4 interact in vivo and in vitro. We have mapped the BLM interacting site to the N-terminus of RECQL4, comprising amino acids 361-478, and the region of BLM encompassing amino acids 1-902 interacts with RECQL4. RECQL4 specifically stimulates BLM helicase activity on DNA fork substrates in vitro. The in vivo interaction between RECQL4 and BLM is enhanced during the S-phase of the cell cycle, and after treatment with ionizing radiation. The retention of RECQL4 at DNA double-strand breaks is shortened in BLM-deficient cells. Further, depletion of RECQL4 in BLM-deficient cells leads to reduced proliferative capacity and an increased frequency of sister chromatid exchanges. Together, our results suggest that BLM and RECQL4 have coordinated activities that promote genome stability.
C1 [Singh, Dharmendra Kumar; Popuri, Venkateswarlu; Kulikowicz, Tomasz; Ghosh, Avik K.; Ramamoorthy, Mahesh; Rossi, Marie L.; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Shevelev, Igor; Janscak, Pavel] Acad Sci Czech Republic, Inst Mol Genet, Prague 14300, Czech Republic.
[Janscak, Pavel] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
RI Janscak, Pavel/G-6189-2014;
OI Ramamoorthy, Mahesh/0000-0002-2359-5647
FU National Institutes of Health Intramural Program of the National
Institute on Aging [Z01-AG000726-17]; Czech Science Foundation
[GAP305/10/0281]; National Institutes of Health
FX National Institutes of Health Intramural Program of the National
Institute on Aging [Z01-AG000726-17]; Czech Science Foundation
[GAP305/10/0281]. Funding for open access charge: National Institutes of
Health.
NR 49
TC 16
Z9 16
U1 0
U2 6
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 AUG
PY 2012
VL 40
IS 14
BP 6632
EP 6648
DI 10.1093/nar/gks349
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 988QD
UT WOS:000307504700029
PM 22544709
ER
PT J
AU Schoenbaum, M
Denchev, P
Vitiello, B
Kaltman, JR
AF Schoenbaum, Michael
Denchev, Peter
Vitiello, Benedetto
Kaltman, Jonathan R.
TI Economic Evaluation of Strategies to Reduce Sudden Cardiac Death in
Young Athletes
SO PEDIATRICS
LA English
DT Article
DE cost-effectiveness; ECG screening; sudden death
ID LONG-QT-SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; COST-EFFECTIVENESS;
OF-CARDIOLOGY; UNITED-STATES; RISK; PREVENTION; CHILDREN;
DEFIBRILLATORS; EPIDEMIOLOGY
AB OBJECTIVE: There is controversy about appropriate methods to reduce sudden cardiac death (SCD) in young athletes, but there is limited evidence on costs or consequences of alternative strategies. The objective of this study was to evaluate the cost-effectiveness of adding electrocardiogram (ECG) screening to the currently standard practice of preparticipation history and physical examination (H&P) to reduce SCD.
METHODS: Decision analysis modeling by using a societal perspective, with annual Markov cycles from age 14 until death. Three screening strategies were evaluated: (1) H&P, with cardiology referral if abnormal (current standard practice); (2) H&P, plus ECG after negative H&P, and cardiology referral if either is abnormal; and (3) ECG only, with cardiology referral if abnormal. Children identified with SCD-associated cardiac abnormalities were restricted from sports and received cardiac treatment. Main outcome measures were costs of screening and treatment, quality-adjusted life years (QALYs), and premature deaths averted.
RESULTS: Relative to strategy 1, incremental cost-effectiveness is $68 800/QALY for strategy 2 and $37 700/QALY for strategy 3. Monte Carlo simulation revealed the chance of incremental cost-effectiveness compared with strategy 1 was 30% for strategy 2 and 66% for strategy 3 (assumed willingness to pay <=$50 000/QALY). Compared with strategy 1, strategy 2 averted 131 additional SCDs at $900 000 per case, and strategy 3 averted 127 SCDs at $600 000 per case.
CONCLUSIONS: Under a societal willingness to pay threshold of $50 000/QALY, adding ECGs to current preparticipation evaluations for athletes is not cost-effective, with costs driven largely by false-positive findings. Pediatrics 2012;130:e380-e389
C1 [Schoenbaum, Michael] NIMH, Off Director, Bethesda, MD 20892 USA.
[Kaltman, Jonathan R.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Schoenbaum, M (reprint author), NIMH, Off Director, 6001 Execut Blvd,Room 8225,MSC 9669, Bethesda, MD 20892 USA.
EM schoenbaumm@mail.nih.gov
NR 47
TC 26
Z9 26
U1 1
U2 10
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2012
VL 130
IS 2
BP E380
EP E389
DI 10.1542/peds.2011-3241
PG 10
WC Pediatrics
SC Pediatrics
GA 983MI
UT WOS:000307123000018
PM 22753553
ER
PT J
AU Gupta, A
Schulze, TG
Nagarajan, V
Akula, N
Corona, W
Jiang, XY
Hunter, N
McMahon, FJ
Detera-Wadleigh, SD
AF Gupta, A.
Schulze, T. G.
Nagarajan, V.
Akula, N.
Corona, W.
Jiang, X-Y
Hunter, N.
McMahon, F. J.
Detera-Wadleigh, S. D.
TI Interaction networks of lithium and valproate molecular targets reveal a
striking enrichment of apoptosis functional clusters and neurotrophin
signaling
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE expression; pathways; MiMI; DAVID; GLay
ID HISTONE DEACETYLASE INHIBITORS; NERVE GROWTH-FACTOR; INCREASES BCL-2
EXPRESSION; GLYCOGEN-SYNTHASE KINASE-3; MICROARRAY GENE-EXPRESSION;
FAMILY-BASED ASSOCIATION; BRAIN MESSENGER-RNA; BIPOLAR DISORDER; SODIUM
VALPROATE; MOOD STABILIZER
AB The overall neurobiological mechanisms by which lithium and valproate stabilize mood in bipolar disorder patients have yet to be fully defined. The therapeutic efficacy and dissimilar chemical structures of these medications suggest that they perturb both shared and disparate cellular processes. To investigate key pathways and functional clusters involved in the global action of lithium and valproate, we generated interaction networks formed by well-supported drug targets. Striking functional similarities emerged. Intersecting nodes in lithium and valproate networks highlighted a strong enrichment of apoptosis clusters and neurotrophin signaling. Other enriched pathways included MAPK, ErbB, insulin, VEGF, Wnt and long-term potentiation indicating a widespread effect of both drugs on diverse signaling systems. MAPK1/3 and AKT1/2 were the most preponderant nodes across pathways suggesting a central role in mediating pathway interactions. The convergence of biological responses unveils a functional signature for lithium and valproate that could be key modulators of their therapeutic efficacy. The Pharmacogenomics Journal (2012) 12, 328-341; doi:10.1038/tpj.2011.9; published online 8 March 2011
C1 [Gupta, A.; Akula, N.; Corona, W.; Jiang, X-Y; Hunter, N.; McMahon, F. J.; Detera-Wadleigh, S. D.] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA.
[Schulze, T. G.] Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany.
[Nagarajan, V.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Detera-Wadleigh, SD (reprint author), NIMH, Human Genet Branch, NIH, 35-1A205,35 Convent Dr, Bethesda, MD 20892 USA.
EM deteras@mail.nih.gov
RI Schulze, Thomas/H-2157-2013;
OI McMahon, Francis/0000-0002-9469-305X
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health.
NR 101
TC 15
Z9 15
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD AUG
PY 2012
VL 12
IS 4
BP 328
EP 341
DI 10.1038/tpj.2011.9
PG 14
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 981CN
UT WOS:000306944300007
PM 21383773
ER
PT J
AU Grossman, JH
McNeil, SE
AF Grossman, Jennifer H.
McNeil, Scoff E.
TI NANOTECHNOLOGY IN CANCER MEDICINE
SO PHYSICS TODAY
LA English
DT Article
ID PEGYLATED-LIPOSOMAL DOXORUBICIN; PHASE-III TRIAL; CARBON NANOTUBES;
BREAST-CANCER; NANOMEDICINE; PACLITAXEL; TOXICOLOGY; TRANSPORT; MICE
C1 [Grossman, Jennifer H.] Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Frederick, MD USA.
[Grossman, Jennifer H.] American Univ, Washington, DC 20016 USA.
RP Grossman, JH (reprint author), Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Frederick, MD USA.
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, National Institutes of Health
FX We thank Pavan Adiseshaiah for helpful discussions about cancer biology
This project has been funded with federal funds from the National Cancer
Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
government.
NR 18
TC 36
Z9 37
U1 3
U2 49
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0031-9228
EI 1945-0699
J9 PHYS TODAY
JI Phys. Today
PD AUG
PY 2012
VL 65
IS 8
BP 38
EP 42
PG 5
WC Physics, Multidisciplinary
SC Physics
GA 990EU
UT WOS:000307614600021
ER
PT J
AU Lodovichi, C
Belluscio, L
AF Lodovichi, Claudia
Belluscio, Leonardo
TI Odorant Receptors in the Formation of the Olfactory Bulb Circuitry
SO PHYSIOLOGY
LA English
DT Review
ID RETINAL GANGLION-CELLS; SENSORY NEURONS; AXON GUIDANCE; GROWTH-CONE;
ELECTRICAL-ACTIVITY; EXPRESSION PATTERNS; ZONAL SEGREGATION; LOCAL
TRANSLATION; GENE-EXPRESSION; NEURAL ACTIVITY
AB In mammals, smell is mediated by odorant receptors expressed by sensory neurons in the nose. These specialized receptors are found both on olfactory sensory neurons' cilia and axon terminals. Although the primary function of ciliary odorant receptors is to detect odorants, their axonal role remains unclear but is thought to involve axon guidance. This review discusses findings that show axonal odorant receptors are indeed functional and capable of modulating neural connectivity.
C1 [Lodovichi, Claudia] Venetian Inst Mol Med, Padua, Italy.
[Lodovichi, Claudia] CNR, Inst Neurosci, Padua, Italy.
[Belluscio, Leonardo] NINDS, Dev Neural Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Lodovichi, C (reprint author), Venetian Inst Mol Med, Padua, Italy.
EM belluscl@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health; Venetian Institute of Molecular Medicine and
Institute of Neuroscience
FX This work was supported by the National Institute of Neurological
Disorders and Stroke, Intramural Research Program at the National
Institutes of Health, and the Venetian Institute of Molecular Medicine
and Institute of Neuroscience.
NR 116
TC 11
Z9 11
U1 0
U2 11
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
J9 PHYSIOLOGY
JI Physiology
PD AUG
PY 2012
VL 27
IS 4
BP 200
EP 212
DI 10.1152/physiol.00015.2012
PG 13
WC Physiology
SC Physiology
GA 991AP
UT WOS:000307673500004
PM 22875451
ER
PT J
AU Henson, MA
Larsen, RS
Lawson, SN
Perez-Otano, I
Nakanishi, N
Lipton, SA
Philpot, BD
AF Henson, Maile A.
Larsen, Rylan S.
Lawson, Shelikha N.
Perez-Otano, Isabel
Nakanishi, Nobuki
Lipton, Stuart A.
Philpot, Benjamin D.
TI Genetic Deletion of NR3A Accelerates Glutamatergic Synapse Maturation
SO PLOS ONE
LA English
DT Article
ID NMDA RECEPTOR SUBUNITS; LONG-TERM POTENTIATION; D-ASPARTATE-RECEPTORS;
DEVELOPING RAT-BRAIN; POSTNATAL-DEVELOPMENT; DIFFERENTIAL EXPRESSION;
REGIONAL EXPRESSION; AMPA RECEPTORS; NR3A-CONTAINING NMDARS; HIPPOCAMPAL
SYNAPSES
AB Glutamatergic synapse maturation is critically dependent upon activation of NMDA-type glutamate receptors (NMDARs); however, the contributions of NR3A subunit-containing NMDARs to this process have only begun to be considered. Here we characterized the expression of NR3A in the developing mouse forebrain and examined the consequences of NR3A deletion on excitatory synapse maturation. We found that NR3A is expressed in many subcellular compartments, and during early development, NR3A subunits are particularly concentrated in the postsynaptic density (PSD). NR3A levels dramatically decline with age and are no longer enriched at PSDs in juveniles and adults. Genetic deletion of NR3A accelerates glutamatergic synaptic transmission, as measured by AMPAR-mediated postsynaptic currents recorded in hippocampal CA1. Consistent with the functional observations, we observed that the deletion of NR3A accelerated the expression of the glutamate receptor subunits NR1, NR2A, and GluR1 in the PSD in postnatal day (P) 8 mice. These data support the idea that glutamate receptors concentrate at synapses earlier in NR3A-knockout (NR3A-KO) mice. The precocious maturation of both AMPAR function and glutamate receptor expression are transient in NR3A-KO mice, as AMPAR currents and glutamate receptor protein levels are similar in NR3A-KO and wildtype mice by P16, an age when endogenous NR3A levels are normally declining. Taken together, our data support a model whereby NR3A negatively regulates the developmental stabilization of glutamate receptors involved in excitatory neurotransmission, synaptogenesis, and spine growth.
C1 [Henson, Maile A.; Philpot, Benjamin D.] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC USA.
[Larsen, Rylan S.; Lawson, Shelikha N.; Philpot, Benjamin D.] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC USA.
[Philpot, Benjamin D.] Univ N Carolina, Neurosci Ctr, Chapel Hill, NC USA.
[Philpot, Benjamin D.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA.
[Perez-Otano, Isabel] CIMA, Dept Neurociencias, Pamplona, Spain.
[Perez-Otano, Isabel] Univ Navarra, E-31080 Pamplona, Spain.
[Nakanishi, Nobuki; Lipton, Stuart A.] Del E Webb Ctr Neurosci Aging & Stem Cell Res, Sanford Burnham Med Res Inst, La Jolla, CA USA.
RP Henson, MA (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
EM maile.henson@nih.gov
OI Larsen, Rylan/0000-0002-7136-1175
FU NARSAD; Marie Curie International Reintegration Program; UTE project
CIMA; MEC [SAF2006-10025]; National Eye Institute [R01 EY018323, R01
EY05477]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development [P01 HD29687]; UNC Charles Lee Raper Dissertation
Fellowship; Society for Neuroscience/NINDS Neuroscience Scholars Program
FX This work was supported by grants from NARSAD (BDP, IPO;
bbrfoundation.org), Marie Curie International Reintegration Program
(http://cordis.europa.eu), UTE project CIMA and MEC (IPO;
SAF2006-10025), National Eye Institute (BDP, R01 EY018323; SAL, R01
EY05477), Eunice Kennedy Shriver National Institute of Child Health and
Human Development (SAL, P01 HD29687), UNC Charles Lee Raper Dissertation
Fellowship (MAH), and the Society for Neuroscience/NINDS Neuroscience
Scholars Program (MAH; http://www.sfn.org/index.aspx?pagename =
NeuroscienceScholars_Main). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 16
Z9 16
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 1
PY 2012
VL 7
IS 8
AR e42327
DI 10.1371/journal.pone.0042327
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 984SU
UT WOS:000307212800081
PM 22870318
ER
PT J
AU Schuck-Paim, C
Viboud, C
Simonsen, L
Miller, MA
Moura, FEA
Fernandes, RM
Carvalho, ML
Alonso, WJ
AF Schuck-Paim, Cynthia
Viboud, Cecile
Simonsen, Lone
Miller, Mark A.
Moura, Fernanda E. A.
Fernandes, Roberto M.
Carvalho, Marcia L.
Alonso, Wladimir J.
TI Were Equatorial Regions Less Affected by the 2009 Influenza Pandemic?
The Brazilian Experience
SO PLOS ONE
LA English
DT Article
ID UNITED-STATES; A H1N1; SEASONAL INFLUENZA; MORTALITY; DEATHS; BURDEN;
WINTER; VIRUS
AB Although it is in the Tropics where nearly half of the world population lives and infectious disease burden is highest, little is known about the impact of influenza pandemics in this area. We investigated the mortality impact of the 2009 influenza pandemic relative to mortality rates from various outcomes in pre-pandemic years throughout a wide range of latitudes encompassing the entire tropical, and part of the subtropical, zone of the Southern Hemisphere (+5 degrees N to -35 degrees S) by focusing on a country with relatively uniform health care, disease surveillance, immunization and mitigation policies: Brazil. To this end, we analyzed laboratory-confirmed deaths and vital statistics mortality beyond pre-pandemic levels for each Brazilian state. Pneumonia, influenza and respiratory mortality were significantly higher during the pandemic, affecting predominantly adults aged 25 to 65 years. Overall, there were 2,273 and 2,787 additional P&I- and respiratory deaths during the pandemic, corresponding to a 5.2% and 2.7% increase, respectively, over average pre-pandemic annual mortality. However, there was a marked spatial structure in mortality that was independent of socio-demographic indicators and inversely related with income: mortality was progressively lower towards equatorial regions, where low or no difference from pre-pandemic mortality levels was identified. Additionally, the onset of pandemic-associated mortality was progressively delayed in equatorial states. Unexpectedly, there was no additional mortality from circulatory causes. Comparing disease burden reliably across regions is critical in those areas marked by competing health priorities and limited resources. Our results suggest, however, that tropical regions of the Southern Hemisphere may have been disproportionally less affected by the pandemic, and that climate may have played a key role in this regard. These findings have a direct bearing on global estimates of pandemic burden and the assessment of the role of immunological, socioeconomic and environmental drivers of the transmissibility and severity of this pandemic.
C1 [Schuck-Paim, Cynthia; Alonso, Wladimir J.] Origem Sci, Sao Paulo, Brazil.
[Viboud, Cecile; Miller, Mark A.; Alonso, Wladimir J.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Sch Publ Hlth, Washington, DC USA.
[Simonsen, Lone] George Washington Univ, Hlth Serv, Washington, DC USA.
[Moura, Fernanda E. A.] Univ Fed Ceara, Virol Lab, Dept Pathol & Med, Fortaleza, Ceara, Brazil.
[Carvalho, Marcia L.] Brazilian Minist Hlth, Hlth Surveillance Secretariat, Brasilia, DF, Brazil.
RP Schuck-Paim, C (reprint author), Origem Sci, Sao Paulo, Brazil.
EM alonsow@mail.nih.gov
RI Moura, Fernanda/I-2739-2013;
OI Simonsen, Lone/0000-0003-1535-8526
FU research program of the Fogarty International Center (National
Institutes of Health); International Influenza Unit, Office of Global
Affairs, United States Department of Health and Human Services; Research
and Policy for Infectious Disease Dynamics program; Fogarty
International Center (National Institutes of Health); Department of
Homeland Security Science and Technology Directorate (United States of
America); Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e
Tecnologico (Brazil)
FX This work was supported by the research program of the Fogarty
International Center (National Institutes of Health) and the
International Influenza Unit, Office of Global Affairs, United States
Department of Health and Human Services. Funding support for Lone
Simonsen came from the Research and Policy for Infectious Disease
Dynamics program, jointly supported by the Fogarty International Center
(National Institutes of Health) and the Department of Homeland Security
Science and Technology Directorate (United States of America). FEAM was
supported by Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e
Tecnologico (Brazil). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 33
TC 14
Z9 14
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 1
PY 2012
VL 7
IS 8
AR e41918
DI 10.1371/journal.pone.0041918
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 984SU
UT WOS:000307212800043
PM 22870262
ER
PT J
AU Abrams, MT
Myers, CS
Feldman, SM
Boddie-Willis, C
Park, J
McMahon, RP
Kelly, DL
AF Abrams, Michael T.
Myers, Carol S.
Feldman, Stephanie M.
Boddie-Willis, Cynthia
Park, Junyong
McMahon, Robert P.
Kelly, Deanna L.
TI Cervical Cancer Screening and Acute Care Visits Among Medicaid Enrollees
With Mental and Substance Use Disorders
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID HEALTH-CARE; ILLNESS; WOMEN; SERVICES; PREVALENCE; MORTALITY; QUALITY;
ABUSE; NEEDS; RISK
AB Objective: This study compared rates of cervical cancer screening and acute care (primary or gynecological) visits among women with and without a diagnosis of psychosis, substance use disorder, bipolar disorder or mania, or depression. Methods: Using data about women (N=105,681) enrolled in Maryland's Medicaid program in fiscal year 2005, the authors constructed logistic models with cancer screening and acute care visits as dependent variables and serious mental illness flags as independent variables. Covariates were age, race, geography, Medicaid eligibility category, and sexually transmitted diseases. The logistic model of cervical cancer screening outcomes was repeated with acute care visits as a covariate. Results: Women with psychosis (N=4,747), bipolar disorder or mania (N=3,319), or depression (N=5,014) were significantly (p<.05) more likely than women in a control group without such disorders (N=85,375) to receive cancer screening (adjusted odds ratio (AOR) range=1.46-1.78) and to have associated acute care visits (AOR range=1.45-2.15). Compared with those in the control group, women with a substance use disorder, with (N=1,104) or without (N=6,122) psychosis, demonstrated reduced odds of cancer screening (AOR=.80) but similar odds of acute care visits (AOR=1.04). Acute care visits were strongly correlated with cancer screens. Genital cancer prevalence did not significantly differ among diagnostic groups. Conclusions: In Maryland Medicaid, the odds of cancer screening and related acute care visits were greater for women with major mental disorders compared with women in the control group. For women with substance use disorders, however, screening was reduced and acute care visits were similar compared with women in the control group. Providers should encourage and support their patients with substance use disorders to increase use of preventive care services by primary care physicians and gynecologists. (Psychiatric Services 63:815 822, 2012; doi: 10.1176/appi.ps.201100301)
C1 [Abrams, Michael T.; Boddie-Willis, Cynthia] Univ Maryland Baltimore Cty, Hilltop Inst, Baltimore, MD 21250 USA.
[Myers, Carol S.] NIDA, Baltimore, MD USA.
[Feldman, Stephanie M.; McMahon, Robert P.; Kelly, Deanna L.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Park, Junyong] Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21250 USA.
RP Abrams, MT (reprint author), Univ Maryland Baltimore Cty, Hilltop Inst, 1000 Hilltop Circle,Sondheim Bldg,3rd Floor, Baltimore, MD 21250 USA.
EM mabrams@hilltop.umbc.edu
RI McMahon, Robert/C-5462-2009
FU National Institute on Drug Abuse (NIDA); NIDA Residential Research
Support Services [HHSN 271200599091CADB]; Maryland's Department of
Health and Mental Hygiene; Bristol-Myers Squibb; Janssen Pharmaceutical
FX This study was supported by the Intramural Research Program, National
Institute on Drug Abuse (NIDA), and NIDA Residential Research Support
Services Contract HHSN 271200599091CADB. The authors thank Nancy Svehla,
R.N., C.P.H.Q., for her early work on their clinical definitions.; Mr.
Abrams and Dr. Boddie-Willis receive substantial financial support from
Maryland's Department of Health and Mental Hygiene. Dr. McMahon has
served as a consultant for Amgen, Inc. Dr. Kelly receives grant support
from Bristol-Myers Squibb and Janssen Pharmaceutical. The other authors
report no competing interests.
NR 46
TC 10
Z9 10
U1 2
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD AUG
PY 2012
VL 63
IS 8
BP 815
EP 822
DI 10.1176/appi.ps.201100301
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 984PX
UT WOS:000307204600014
PM 22660581
ER
PT J
AU Clarke, K
Tchabanenko, K
Pawlosky, R
Carter, E
King, MT
Musa-Veloso, K
Ho, M
Roberts, A
Robertson, J
VanItallie, TB
Veech, RL
AF Clarke, Kieran
Tchabanenko, Kirill
Pawlosky, Robert
Carter, Emma
King, M. Todd
Musa-Veloso, Kathy
Ho, Manki
Roberts, Ashley
Robertson, Jeremy
VanItallie, Theodore B.
Veech, Richard L.
TI Kinetics, safety and tolerability of (R)-3-hydroxybutyl
(R)-3-hydroxybutyrate in healthy adult subjects
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE (R)-3-hydroxybutyl (R)-3-hydroxybutyrate; Ketone; beta-Hydroxybutyrate;
Acetoacetate; Kinetics; Safety; Tolerability
ID KETONE-BODY KINETICS; BETA-HYDROXYBUTYRATE; DIABETIC-KETOACIDOSIS;
ACETOACETATE; BODIES; METABOLISM; RAT; STARVATION; INSULIN; BRAIN
AB Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of beta-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2 h, reaching 3.30 mM and 1.19 mM for beta-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1 h for beta-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Clarke, Kieran; Carter, Emma] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Tchabanenko, Kirill; Robertson, Jeremy] Univ Oxford, Dept Chem, Oxford, England.
[Pawlosky, Robert; King, M. Todd; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA.
[Musa-Veloso, Kathy; Ho, Manki; Roberts, Ashley] Intertek Cantox, Mississauga, ON, Canada.
[VanItallie, Theodore B.] Columbia Univ, Dept Med, St Lukes Roosevelt Hosp Ctr, Coll Phys & Surg, New York, NY USA.
RP Clarke, K (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Sherrington Bldg,Parks Rd, Oxford OX1 3PT, England.
EM kieran.clarke@dpag.ox.ac.uk
FU DARPA; TdeltaS Limited; Defense Advanced Research Projects Agency
(DARPA) of the United States
FX The intellectual property covering the uses of ketone bodies and ketone
esters are owned by BTG Ltd., the University of Oxford and the National
Institutes of Health. Should royalties ever accrue from these patents,
Dr. Richard L. Veech, Professor Kieran Clarke, and Mr. Todd King, as
inventors, will receive a share of the royalties under the terms
prescribed by each institution. Professor Kieran Clarke is a
non-executive director of TdeltaS Ltd., a company spun out of the
University of Oxford to develop products based on the science of ketone
bodies in human nutrition. Drs Kathy Musa-Veloso, Manki Ho, and Ashley
Roberts received financial support from DARPA and TdeltaS Limited for
consulting services and manuscript preparation.; The authors thank the
Defense Advanced Research Projects Agency (DARPA) of the United States
for funding this work.
NR 30
TC 35
Z9 35
U1 6
U2 19
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD AUG
PY 2012
VL 63
IS 3
BP 401
EP 408
DI 10.1016/j.yrtph.2012.04.008
PG 8
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 980IC
UT WOS:000306885800006
PM 22561291
ER
PT J
AU Harries, LW
Bradley-Smith, RM
Llewellyn, DJ
Pilling, LC
Fellows, A
Henley, W
Hernandez, D
Guralnik, JM
Bandinelli, S
Singleton, A
Ferrucci, L
Melzer, D
AF Harries, Lorna W.
Bradley-Smith, Rachel M.
Llewellyn, David J.
Pilling, Luke C.
Fellows, Alexander
Henley, William
Hernandez, Dena
Guralnik, Jack M.
Bandinelli, Stefania
Singleton, Andrew
Ferrucci, Luigi
Melzer, David
TI Leukocyte CCR2 Expression Is Associated with Mini-Mental State
Examination Score in Older Adults
SO REJUVENATION RESEARCH
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; MONOCYTE CHEMOATTRACTANT PROTEIN-1;
ALZHEIMERS-DISEASE; REDUCES ATHEROSCLEROSIS; GENE-EXPRESSION; DEFICIENT
MICE; DECLINE; INFLAMMATION; PLASMA; PROGRESSION
AB Introduction: Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample.
Methods: We measured in vivo transcript levels by microarray analysis in 691 subjects (mean age 72.6 years) in the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area). We assessed expression associations with MMSE performance at RNA collection and prior 9-year change in MMSE score in linear regression models.
Results: In genome-wide analysis, raised CCR2 expression was cross-sectionally the most strongly associated transcript with lower MMSE score (beta = -0.16, p = 5.1 x 10(-6), false discovery rate (FDR; q =0.077). Amongst inflammatory transcripts, only CCR2 expression was associated with both MMSE score and accelerated decline in score over the preceding 9 years (beta = -0.16, p = 5.1 x 10(-6), q = 0.003; and beta = 0.13, p = 5.5 x 10(-5), q = -0.03, respectively). CCR2 expression was also positively associated with apolipoprotein E (ApoE) e4 Alzheimer disease risk haplotype.
Conclusions: We show for the first time that CCR2 expression is associated with lower MMSE scores in an older human population. Laboratory models of Ccr2-mediated beta-amyloid removal and regulation of neurogenesis affecting cognitive function may be applicable in humans. CCR2-mediated pathways may provide a possible focus for intervention to potentiate protective reactions to Alzheimer pathology in older people, including for people with an adverse ApoE haplotype.
C1 [Harries, Lorna W.; Bradley-Smith, Rachel M.; Llewellyn, David J.; Fellows, Alexander] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Pilling, Luke C.; Melzer, David] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Henley, William] Univ Plymouth, Ctr Hlth & Environm Stat, Plymouth PL4 8AA, Devon, England.
[Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Ferrucci, Luigi] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD USA.
RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Pilling, Luke/E-4917-2013; Harries, Lorna/D-2241-2014; Singleton,
Andrew/C-3010-2009;
OI Pilling, Luke/0000-0002-3332-8454; Melzer, David/0000-0002-0170-3838
FU National Institute on Aging; U.S. National Institutes of Health;
National Institute of Health Research (NIHR)
FX This study was supported in part by the Intramural Research Program,
National Institute on Aging, and the U.S. National Institutes of Health.
We thank the many people who contributed to the InCHIANTI study,
including all of the anonymous participants. The U.S. National Institute
on Aging intramural research program contributed the array data and
supported this analysis. William Henley completed this work while
seconded to PenCLARHC, which is funded by the National Institute of
Health Research (NIHR). The views expressed in this publication are
those of the author(s) and not necessarily those of the National Health
Service (NHS), the NIHR, or the Department of Health.
NR 38
TC 10
Z9 10
U1 1
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
EI 1557-8577
J9 REJUV RES
JI Rejuv. Res.
PD AUG
PY 2012
VL 15
IS 4
BP 395
EP 404
DI 10.1089/rej.2011.1302
PG 10
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 990IH
UT WOS:000307623700007
PM 22607625
ER
PT J
AU Swindell, WR
Cummings, SR
Sanders, JL
Caserotti, P
Rosano, C
Satterfield, S
Strotmeyer, ES
Harris, TB
Simonsick, EM
Cawthon, PM
AF Swindell, William R.
Cummings, Steven R.
Sanders, Jason L.
Caserotti, Paolo
Rosano, Caterina
Satterfield, Suzanne
Strotmeyer, Elsa S.
Harris, Tamara B.
Simonsick, Eleanor M.
Cawthon, Peggy M.
TI Data Mining Identifies Digit Symbol Substitution Test Score and Serum
Cystatin C as Dominant Predictors of Mortality in Older Men and Women
SO REJUVENATION RESEARCH
LA English
DT Article
ID BODY-COMPOSITION; CARDIOVASCULAR HEALTH; 5-YEAR MORTALITY;
DECISION-MAKING; ELDERLY PERSONS; RISK-FACTORS; ADULTS; DISABILITY;
ASSOCIATION; PERFORMANCE
AB Background: Characterization of long-term health trajectory in older individuals is important for proactive health management. However, the relative prognostic value of information contained in clinical profiles of nonfrail older adults is often unclear.
Methods: We screened 825 phenotypic and genetic measures evaluated during the Health, Aging, and Body Composition Study (Health ABC) baseline visit (3,067 men and women aged 70-79). Variables that best predicted mortality over 13 years of follow-up were identified using 10-fold cross-validation.
Results: Mortality was most strongly associated with low Digit Symbol Substitution Test (DSST) score (DSST <25; 21.9% of cohort; hazard ratio [HR] = 1.87 +/- 0.06) and elevated serum cystatin C (>= 1.30 mg/mL; 12.1% of cohort; HR = 2.25 +/- 0.07). These variables predicted mortality better than 823 other measures, including baseline age and a 45-variable health deficit index. Given elevated cystatin C (>= 1.30 mg/mL), mortality risk was further increased by high serum creatinine, high abdominal visceral fat density, and smoking history (2.52 <= HR <= 3.73). Given a low DSST score (<25) combined with low-to-moderate cystatin C (< 1.30 mg/mL), mortality risk was highest among those with elevated plasma resistin and smoking history (1.90 <= HR <= 2.02).
Conclusions: DSST score and serum cystatin C warrant priority consideration for the evaluation of mortality risk in older individuals. Both variables, taken individually, predict mortality better than chronological age or a health deficit index in well-functioning older adults (ages 70-79). DSST score and serum cystatin C can thus provide evidence-based tools for geriatric assessment.
C1 [Swindell, William R.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Cummings, Steven R.; Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Sanders, Jason L.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Sanders, Jason L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Caserotti, Paolo] Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Caserotti, Paolo; Harris, Tamara B.; Simonsick, Eleanor M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Swindell, WR (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,Room 0464, Boston, MA 02115 USA.
EM wswindell@genetics.med.harvard.edu
RI Strotmeyer, Elsa/F-3015-2014;
OI Rosano, Caterina/0000-0002-0909-1506; Strotmeyer,
Elsa/0000-0002-4093-6036; Rosano, Caterina/0000-0002-4271-6010
FU National Institute of Aging, National Institutes of Health, Bethesda, MD
[N01-AG-6-2101, N01-AG-6- 2103, N01-AG-6-2106]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Aging, National Institutes of Health,
Bethesda, MD (contracts N01-AG-6- 2101, N01-AG-6- 2103, and
N01-AG-6-2106). We thank two anonymous reviewers for providing
constructive comments and suggestions on this manuscript.
NR 28
TC 2
Z9 2
U1 0
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
J9 REJUV RES
JI Rejuv. Res.
PD AUG
PY 2012
VL 15
IS 4
BP 405
EP 413
DI 10.1089/rej.2011.1297
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 990IH
UT WOS:000307623700008
PM 22607624
ER
PT J
AU Melnick, RL
Burns, KM
Ward, JM
Huff, J
AF Melnick, Ronald L.
Burns, Kathleen M.
Ward, Jerrold M.
Huff, James
TI Chemically Exacerbated Chronic Progressive Nephropathy Not Associated
with Renal Tubular Tumor Induction in Rats: An Evaluation Based on 60
Carcinogenicity Studies by the National Toxicology Program
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE nephropathy severity; renal tubule tumors; kidney; rats; carcinogenicity
studies; aging nephropathy; chronic progressive nephropathy
ID MALE F344 RATS; HUMAN RISK-ASSESSMENT; ALPHA-2U-GLOBULIN NEPHROPATHY;
CELL-PROLIFERATION; ORGANIC-SOLVENTS; CHRONIC TOXICITY; BODY-WEIGHT;
KIDNEY; FIBROSIS; SURVIVAL
AB Chronic progressive nephropathy (CPN) is a common age-related degenerative regenerative disease of the kidney that occurs in both sexes of most strains of rats. Recently, claims have been made that enhanced CPN is a mode of action for chemically induced kidney tumors in male rats and that renal tubular tumors (RTTs) induced by chemicals that concomitantly exacerbate CPN are not relevant for human cancer risk assessments. Although CPN is an observable histopathological lesion that may be modified by diet, the etiology of this disease and the mechanisms for its exacerbation by chemicals are unknown, and it fails to meet fundamental principles for defining carcinogenic modes of action and human relevance. Our comprehensive evaluation of possible relationships between exacerbated CPN and induction of RTTs in 58 carcinogenicity studies, conducted by the National Toxicology Program, in male and 11 studies in female F344 rats using 60 chemicals revealed widespread inconsistency in the claimed association. Because the proposed hypothesis lacks evidence of biological plausibility, and due to inconsistent relationships between exacerbated CPN and kidney tumor incidence in carcinogenicity studies in rats, dismissing the human relevance of kidney tumors induced by chemicals that also exacerbate CPN in rats would be wrong.
C1 [Melnick, Ronald L.] Ron Melnick Consulting LLC, Chapel Hill, NC 27514 USA.
[Burns, Kathleen M.] Sciencecorps LLC, Lexington, MA 02420 USA.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD 20886 USA.
[Huff, James] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Melnick, RL (reprint author), 111 Roundtree Rd, Chapel Hill, NC 27514 USA.
EM ron.melnick@gmail.com
NR 43
TC 4
Z9 4
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2012
VL 128
IS 2
BP 346
EP 356
DI 10.1093/toxsci/kfs156
PG 11
WC Toxicology
SC Toxicology
GA 991JY
UT WOS:000307698500005
PM 22539614
ER
PT J
AU Hall, J
Haas, KL
Freedman, JH
AF Hall, Julie
Haas, Kathryn L.
Freedman, Jonathan H.
TI Role of MTL-1, MTL-2, and CDR-1 in Mediating Cadmium Sensitivity in
Caenorhabditis elegans
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE Caenorhabditis elegans; metallothionein; cadmium; phytochelatin
ID METALLOTHIONEIN-II GENES; MOLECULAR CHARACTERIZATION; TOXICITY;
NEMATODE; GLUTATHIONE; CELLS; RESISTANCE; PHYTOCHELATINS;
IDENTIFICATION; EXPRESSION
AB Cadmium is an environmental toxicant whose exposure is associated with multiple human pathologies. To prevent cadmium-induced toxicity, organisms produce a variety of detoxification molecules. In response to cadmium, the nematode Caenorhabditis elegans increases the steady-state levels of several hundred genes, including two metallothioneins, mtl-1 and mtl-2, and the cadmium-specific response gene, cdr-1. Despite the presumed importance in metal detoxification of mtl-1 and mtl-2, knockdown of their expression does not increase cadmium hypersensitivity, which suggests that these genes are not required for resistance to metal toxicity in C. elegans. To determine whether cdr-1 is critical in metal detoxification and compensates for the loss of mtl-1 and/or mtl-2, C. elegans strains were generated in which one, two, and all three genes were deleted, and the effects of cadmium on brood size, embryonic lethality, the Bag phenotype, and growth were determined. Growth at low cadmium concentrations was the only endpoint in which the triple mutant displayed more sensitivity than the single and double mutants. A lack of hypersensitivity in these strains suggests that other factors may be involved in the response to cadmium. Caenorhabditis elegans produces phytochelatins (PCs) that are critical in the defense against cadmium toxicity. PC levels in wild type, cdr-1 single, mtl-1, mtl-2 double, and triple mutants were measured. PC levels were constitutively higher in the mtl-1, mtl-2 double, and triple mutants compared with wild type. Following cadmium exposure, PC levels increased. The lack of cadmium hypersensitivity when these genes are deleted may be attributed to the compensatory effects of increases in PCs.
C1 [Haas, Kathryn L.; Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Hall, Julie; Freedman, Jonathan H.] NIEHS, Biomol Screening Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, Mail Drop E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
FU National Institutes of Health National Center for Research Resources;
National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES102045, Z01ES102046]
FX Nematode strains used in this work were provided by the Caenorhabditis
Genetics Center, which is funded by the National Institutes of Health
National Center for Research Resources. This research was supported (in
part) by the Intramural Research Program of the National Institutes of
Health, National Institute of Environmental Health Sciences (Z01ES102045
and Z01ES102046).
NR 34
TC 10
Z9 13
U1 3
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2012
VL 128
IS 2
BP 418
EP 426
DI 10.1093/toxsci/kfs166
PG 9
WC Toxicology
SC Toxicology
GA 991JY
UT WOS:000307698500011
PM 22552775
ER
PT J
AU Wang, JB
Lu, JY
Mook, RA
Zhang, M
Zhao, SL
Barak, LS
Freedman, JH
Lyerly, HK
Chen, W
AF Wang, Jiangbo
Lu, Jiuyi
Mook, Robert A., Jr.
Zhang, Min
Zhao, Shengli
Barak, Larry S.
Freedman, Jonathan H.
Lyerly, H. Kim
Chen, Wei
TI The Insecticide Synergist Piperonyl Butoxide Inhibits Hedgehog
Signaling: Assessing Chemical Risks
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE piperonyl butoxide; Smoothened antagonist; Hedgehog signal transduction
pathway; high throughput screening; chemical risk assessment
ID SONIC HEDGEHOG; IN-VITRO; MICE; TOXICITY; PATHWAY; GROWTH; BRAIN; RATS;
HEPATOCARCINOGENESIS; BETA-ARRESTIN-2
AB The spread of chemicals, including insecticides, into the environment often raises public health concerns, as exemplified by a recent epidemiologic study associating in utero piperonyl butoxide (PBO) exposure with delayed mental development. The insecticide synergist PBO is listed among the top 10 chemicals detected in indoor dust; a systematic assessment of risks from PBO exposure, as for many toxicants unfortunately, may be underdeveloped when important biological targets that can cause toxicity are unknown. Hedgehog/Smoothened signaling is critical in neurological development. This study was designed to use novel high-throughput in vitro drug screening technology to identify modulators of Hedgehog signaling in environmental chemicals to assist the assessment of their potential risks. A directed library of 1408 environmental toxicants was screened for Hedgehog/Smoothened antagonist activity using a high-content assay that evaluated the interaction between Smoothened and beta arrestin2 green fluorescent protein. PBO was identified as a Hedgehog/Smoothened antagonist capable of inhibiting Hedgehog signaling. We found that PBO bound Smoothened and blocked Smoothened overexpression induced Gli-luciferase reporter activity but had no effect on Gli-1 downstream transcriptional factor induced Gli activity. PBO inhibited Sonic Hedgehog ligand induced Gli signaling and mouse cerebellar granular precursor cell proliferation. Moreover, PBO disrupted zebrafish development. Our findings demonstrate the value of high-throughput target-based screening strategies that can successfully evaluate large numbers of environmental toxicants and identify key targets and unknown biological activity that is helpful in properly assessing potential risks.
C1 [Wang, Jiangbo; Lu, Jiuyi; Mook, Robert A., Jr.; Zhang, Min; Zhao, Shengli; Chen, Wei] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Barak, Larry S.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Lyerly, H. Kim] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
RP Chen, W (reprint author), Duke Univ, Med Ctr, Dept Med, Room 1073C,Genome Sci Res Bldg 1,595 LaSalle St, Durham, NC 27710 USA.
EM w.chen@duke.edu
RI Lyerly, Herbert/B-6528-2014
OI Lyerly, Herbert/0000-0002-0063-4770
FU National Institutes of Health [5R01CA113656-03]; Fred and Alice
Stanback; National Institute of Environmental Health Sciences, National
Institutes of Health [Z01ES102045]
FX National Institutes of Health (5R01CA113656-03 to W.C.); Fred and Alice
Stanback (H.K.L.); the Intramural Research Program of the National
Institute of Environmental Health Sciences, National Institutes of
Health (Z01ES102045 to J.H.F).
NR 38
TC 5
Z9 6
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2012
VL 128
IS 2
BP 517
EP 523
DI 10.1093/toxsci/kfs165
PG 7
WC Toxicology
SC Toxicology
GA 991JY
UT WOS:000307698500020
PM 22552772
ER
PT J
AU Vanpouille, C
Arakelyan, A
Margolis, L
AF Vanpouille, Christophe
Arakelyan, Anush
Margolis, Leonid
TI Microbicides: still a long road to success
SO TRENDS IN MICROBIOLOGY
LA English
DT Review
DE microbicide; HIV-1; tenofovir; pre-exposure prophylaxis
ID TENOFOVIR DISOPROXIL FUMARATE; IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED
CONTROLLED-TRIAL; VAGINAL SHIV TRANSMISSION; MUCOSAL HIV TRANSMISSION;
FEMALE GENITAL-TRACT; IN-VITRO; PREEXPOSURE PROPHYLAXIS; EX-VIVO; SEXUAL
TRANSMISSION
AB The development of efficient microbicides, the topically applied compounds that protect uninfected individuals from acquiring HIV-1, is a promising strategy to contain HIV-1 epidemics. Such microbicides should of course possess anti-HIV-1 activity, but they should also act against other genital pathogens, which facilitate HIV-1 transmission. The new trend in microbicide strategy is to use drugs currently used in HIV-1 therapy. The success of this strategy is mixed so far and is impaired by our limited knowledge of the basic mechanisms of HIV-1 transmission as well as by the inadequacy of the systems in which microbicides are tested in preclinical studies.
C1 [Vanpouille, Christophe; Arakelyan, Anush; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM margolis@helix.nih.gov
FU National Institute of Child Health and Human Development (NICHD)
Intramural Program
FX This work was supported by the National Institute of Child Health and
Human Development (NICHD) Intramural Program. We are grateful to Dr
Robin Shattock for critical remarks and helpful comments and to Jeremy
Swan, Melissa Sisk, and Yumiko Shepherd for their generous assistance in
preparation of the figures.
NR 85
TC 16
Z9 18
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0966-842X
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD AUG
PY 2012
VL 20
IS 8
BP 369
EP 375
DI 10.1016/j.tim.2012.05.005
PG 7
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 992TN
UT WOS:000307802700004
PM 22705107
ER
PT J
AU Jenkins, RA
AF Jenkins, Richard A.
TI Recruiting Substance-Using Men Who Have Sex With Men into HIV Prevention
Research: Current Status and Future Directions
SO AIDS AND BEHAVIOR
LA English
DT Review
DE MSM; Recruitment; Methodology; Sampling
ID RISK BEHAVIORS; BLACK-MEN; INFECTION; POPULATIONS; ONLINE; ISSUES;
ADULTS
AB Research investigators have identified increasing challenges to the recruitment of men who have sex with men (MSM) for observational and intervention HIV/AIDS studies. To address these issues, program staff from the National Institute on Drug Abuse convened a meeting on April 28th to 29th, 2009 to discuss issues in MSM recruitment. The panel indicated that there was decreased community identification with HIV research, although altruistic, community-oriented motives continued to be important. Substance use adds to recruitment challenges, particularly recruitment of MSM who use stigmatized substances. Relatively new recruitment methods such as respondent driven sampling, venue-data-time sampling, and internet sampling have helped advance knowledge about the recruitment process; however, they have not mitigated the challenges to MSM recruitment. Recruitment of youth and members of racial/ethnic minority populations present additional considerations. This report summarizes the meeting's proceedings, key points of discussion, and areas for further research consideration.
C1 Natl Inst Drug Abuse, Prevent Res Branch, Bethesda, MD 20892 USA.
RP Jenkins, RA (reprint author), Natl Inst Drug Abuse, Prevent Res Branch, 6001 Execut Blvd,Rm 5185,MSC 9589, Bethesda, MD 20892 USA.
EM jenkinsri@mail.nih.gov
NR 34
TC 13
Z9 13
U1 0
U2 5
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 AUG
PY 2012
VL 16
IS 6
BP 1411
EP 1419
DI 10.1007/s10461-011-0037-5
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 977WI
UT WOS:000306695100005
PM 22016329
ER
PT J
AU Kreitchmann, R
Harris, DR
Kakehasi, F
Haberer, JE
Cahn, P
Losso, M
Teles, E
Pilotto, JH
Hofer, CB
Read, JS
AF Kreitchmann, Regis
Harris, D. Robert
Kakehasi, Fabiana
Haberer, Jessica E.
Cahn, Pedro
Losso, Marcelo
Teles, Elizabete
Pilotto, Jose H.
Hofer, Cristina B.
Read, Jennifer S.
CA NISDI LILAC Study Team
TI Antiretroviral Adherence During Pregnancy and Postpartum in Latin
America
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SELF-REPORTED ADHERENCE; WOMENS
INTERAGENCY HIV; MEDICATION ADHERENCE; THERAPY ADHERENCE; INFECTED
WOMEN; DRUG-USE; ASSOCIATION; HAART; NONADHERENCE
AB Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p < 0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR] = 2.9, 95% confidence interval [CI]: 1.46-6.14; p = 0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR = 1.06, 95% CI: 1.00-1.12, p = 0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR = 3.04, 95% CI: 1.34-6.90; p = 0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.
C1 [Kreitchmann, Regis] Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil.
[Harris, D. Robert] WESTAT Corp, Rockville, MD 20850 USA.
[Kakehasi, Fabiana] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cahn, Pedro] Hosp Gen Agudos Juan A Fernandez, Buenos Aires, DF, Argentina.
[Losso, Marcelo] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, DF, Argentina.
[Teles, Elizabete] Hosp Femina Grp Hosp Conceicao, Porto Alegre, RS, Brazil.
[Pilotto, Jose H.] Hosp Geral Nova Iguacu HIV Family Care Clin, Rio De Janeiro, Brazil.
[Pilotto, Jose H.] Lab AIDS & Imunol Mol IOC Fiocruz, Rio De Janeiro, Brazil.
[Hofer, Cristina B.] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil.
[Hofer, Cristina B.] Univ Fed Rio de Janeiro, Dept Prevent Med, Rio De Janeiro, Brazil.
[Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
RP Kreitchmann, R (reprint author), STD AIDS Municipal Ctr, Hlth Secretary, Manoel Lobato 151, Porto Alegre, RS, Brazil.
EM regis.kr@terra.com.br
RI Mussi-Pinhata, Marisa/G-6568-2012; Inca, Inct/K-2204-2013
FU NICHD NIH HHS [N01-HD-3-3345, N01-HD-8-0001]; PHS HHS
[HHSN267200800001C]
NR 34
TC 20
Z9 20
U1 1
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD AUG
PY 2012
VL 26
IS 8
BP 486
EP 495
DI 10.1089/apc.2012.0013
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 983KS
UT WOS:000307118800007
PM 22663185
ER
PT J
AU Fertig, JB
Ryan, ML
Falk, DE
Litten, RZ
Mattson, ME
Ransom, J
Rickman, WJ
Scott, C
Ciraulo, D
Green, AI
Tiouririne, NA
Johnson, B
Pettinati, H
Strain, EC
Devine, E
Brunette, MF
Kampman, K
Tompkins, DA
Stout, R
AF Fertig, Joanne B.
Ryan, Megan L.
Falk, Daniel E.
Litten, Raye Z.
Mattson, Margaret E.
Ransom, Janet
Rickman, William J.
Scott, Charles
Ciraulo, Domenic
Green, Alan I.
Tiouririne, Nassima A.
Johnson, Bankole
Pettinati, Helen
Strain, Eric C.
Devine, Eric
Brunette, Mary F.
Kampman, Kyle
Tompkins, David A.
Stout, Robert
CA NCIG Study Grp
TI A Double-Blind, Placebo-Controlled Trial Assessing the Efficacy of
Levetiracetam Extended-Release in Very Heavy Drinking Alcohol-Dependent
Patients
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Dependence; Levetiracetam; Keppra (R); Medications Development;
Alcohol Use Disorder
ID ANTIEPILEPTIC DRUG LEVETIRACETAM; USE DISORDERS; ANTICONVULSANT DRUG;
WITHDRAWAL SYNDROME; OPEN-LABEL; TOPIRAMATE; CONSUMPTION; GABAPENTIN;
PROFILE
AB Background Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers. Methods In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16. Results No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001). Conclusions This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.
C1 [Fertig, Joanne B.; Ryan, Megan L.; Falk, Daniel E.; Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA.
[Mattson, Margaret E.] Subst Abuse & Mental Hlth Serv Adm SAMHSA, Ctr Behav Hlth Stat & Qual, Rockville, MD USA.
[Ransom, Janet; Rickman, William J.; Scott, Charles] FastTrack Drugs & Biol, N Potomac, MD USA.
[Ciraulo, Domenic; Devine, Eric] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Green, Alan I.] Dartmouth Med Sch DHMC, Dept Psychiat, Lebanon, NH USA.
[Tiouririne, Nassima A.] Univ Virginia, Ctr Addict Res & Educ, Richmond, VA USA.
[Johnson, Bankole] Univ Virginia, Dept Psychiat Med, Ctr Addict Res & Educ, Charlottesville, VA USA.
[Pettinati, Helen; Kampman, Kyle] Univ Penn, Treatment Res Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Strain, Eric C.; Tompkins, David A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Brunette, Mary F.] Dartmouth Med Sch, Dept Psychiat, Psychopharmacol Res Grp, Concord, NH USA.
[Stout, Robert] Decis Sci Inst PIRE, Pawtucket, RI USA.
RP Fertig, JB (reprint author), Natl Inst Alcohol & Alcoholism, NIH, 5635 Fishers Lane,Room 2041, Rockville, MD 20852 USA.
EM jfertig@mail.nih.gov
OI Ciraulo, Domenic/0000-0001-7706-8765
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, Department of Health and Human Services
FX This research was supported by the National Institute on Alcohol Abuse
and Alcoholism, National Institutes of Health, Department of Health and
Human Services. Fast Track Drugs and Biologics was the Data Coordinating
Center.
NR 39
TC 26
Z9 26
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG
PY 2012
VL 36
IS 8
BP 1421
EP 1430
DI 10.1111/j.1530-0277.2011.01716.x
PG 10
WC Substance Abuse
SC Substance Abuse
GA 981WN
UT WOS:000307003400015
PM 22324516
ER
PT J
AU Tobias, DK
Zhang, CL
Chavarro, J
Bowers, K
Rich-Edwards, J
Rosner, B
Mozaffarian, D
Hu, FB
AF Tobias, Deirdre K.
Zhang, Cuilin
Chavarro, Jorge
Bowers, Katherine
Rich-Edwards, Janet
Rosner, Bernard
Mozaffarian, Dariush
Hu, Frank B.
TI Prepregnancy adherence to dietary patterns and lower risk of gestational
diabetes mellitus
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; MEDITERRANEAN
DIET; RANDOMIZED-TRIAL; YOUNGER WOMEN; GLYCEMIC LOAD; METAANALYSIS;
VALIDITY; QUALITY; VALIDATION
AB Background: Previous studies observed inverse associations of adherence to the alternate Mediterranean (aMED), Dietary Approaches to Stop Hypertension (DASH), and alternate Healthy Eating Index (aHEI) dietary patterns with risk of type 2 diabetes; however, their associations with gestational diabetes mellitus (GDM) risk are unknown.
Objective: This study aimed to assess usual prepregnancy adherence to well-known dietary patterns and GDM risk.
Design: Our study included 21,376 singleton live births reported from 15,254 participants of the Nurses' Health Study II cohort between 1991 and 2001. Pregnancies were free of prepregnancy chronic disease or previous GDM. Prepregnancy dietary pattern adherence scores were computed based on participants' usual intake of the patterns' components, assessed with a validated food-frequency questionnaire. Multivariable logistic regressions with generalized estimating equations were used to estimate the RRs and 95% CIs.
Results: Incident first-time GDM was reported in 872 pregnancies. All 3 scores were inversely associated with GDM risk after adjustment for several covariables. In a comparison of the multivariable risk of GDM in participants in the fourth and first quartiles of dietary pattern adherence scores, aMED was associated with a 24% lower risk (RR: 0.76; 95% CI: 0.60, 0.95; P-trend = 0.004), DASH with a 34% lower risk (RR: 0.66; 95% CI: 0.53, 0.82; P-trend = 0.0005), and aHEI with a 46% lower risk (RR: 0.54; 95% CI: 0.43, 0.68; P-trend < 0.0001).
Conclusion: Prepregnancy adherence to healthful dietary patterns is significantly associated with a lower risk of GDM. Am J Clin Nutr 2012;96:289-95.
C1 [Tobias, Deirdre K.; Chavarro, Jorge; Mozaffarian, Dariush; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Tobias, Deirdre K.; Chavarro, Jorge; Rich-Edwards, Janet; Mozaffarian, Dariush; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Zhang, Cuilin; Bowers, Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Chavarro, Jorge; Rich-Edwards, Janet; Rosner, Bernard; Mozaffarian, Dariush] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Rich-Edwards, Janet] Brigham & Womens Hosp, Dept Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Tobias, DK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM dbanel@hsph.harvard.edu; zhangcu@mail.nih.gov
RI Bowers, Katherine/N-5226-2015
FU Intramural Research Program of the Eunice Kennedy Slither National
Institute of Child Health and Human Development, NIH; [DK58845];
[CA50385]; [P30 DK46200-18]
FX Supported by grants DK58845, CA50385, and P30 DK46200-18. CZ and KB were
supported by the Intramural Research Program of the Eunice Kennedy
Slither National Institute of Child Health and Human Development, NIH.
NR 42
TC 38
Z9 40
U1 1
U2 17
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2012
VL 96
IS 2
BP 289
EP 295
DI 10.3945/ajcn.111.028266
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 978TW
UT WOS:000306769700011
PM 22760563
ER
PT J
AU Sinha, R
Cross, AJ
Daniel, CR
Graubard, BI
Wu, JW
Hollenbeck, AR
Gunter, MJ
Park, Y
Freedman, ND
AF Sinha, Rashmi
Cross, Amanda J.
Daniel, Carrie R.
Graubard, Barry I.
Wu, Jennifer W.
Hollenbeck, Albert R.
Gunter, Marc J.
Park, Yikyung
Freedman, Neal D.
TI Caffeinated and decaffeinated coffee and tea intakes and risk of
colorectal cancer in a large prospective study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; PROSPECTIVE COHORT;
CHLOROGENIC ACID; NATIONAL-INSTITUTES; PARKINSONS-DISEASE; COMPONENTS
KAHWEOL; RECTAL-CANCER; FOLLOW-UP; CONSUMPTION
AB Background: Coffee and tea are widely consumed globally and are rich sources of potential chemopreventive compounds. Epidemiologic data for coffee and tea intakes in relation to colorectal cancer remain unclear. Despite differences in gut physiology, few studies have conducted investigations by anatomic subsites.
Objective: We evaluated coffee and tea intakes (caffeinated and decaffeinated) in relation to colon (proximal and distal) and rectal cancers.
Design: The NIH-AARP Diet and Health Study included 489,706 men and women who completed a baseline (1995-1996) self-administered questionnaire of demographics, diet, and lifestyle. Over a median of 10.5 y of follow-up, we identified 2863 proximal colon, 1993 distal colon, and 1874 rectal cancers. Multivariable HRs and 95% CIs were estimated by using Cox regression.
Results: Approximately 16% of participants drank >= 4 cups coffee/d. Compared with nondrinkers, drinkers of 4-5 cups coffee/d (HR: 0.85; 95% CI: 0.75, 0.96) and >= 6 cups coffee/d (HR: 0.74; 95% CI: 0.61, 0.89; P-trend < 0.001) had a lower risk of colon cancer, particularly of proximal tumors (HR for >= 6 cups/d: 0.62; 95% CI: 0.49, 0.81; P-trend < 0.0001). Results were similar to those overall for drinkers of predominantly caffeinated coffee. Although individual HRs were not significant, there was a significant P-trend for both colon and rectal cancers for people who drank predominantly decaffeinated coffee. No associations were observed for tea.
Conclusions: In this large US cohort, coffee was inversely associated with colon cancer, particularly proximal tumors. Additional investigations of coffee intake and its components in the prevention of colorectal cancer by subsites are warranted. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015. Am J Clin Nutr 2012;96:374-81.
C1 [Sinha, Rashmi; Cross, Amanda J.; Daniel, Carrie R.; Wu, Jennifer W.; Park, Yikyung; Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
RP Sinha, R (reprint author), 6120 Execut Blvd, Rockville, MD 20852 USA.
EM sinhar@nih.gov
RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098;
Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the National Cancer Institute, NIH
FX Supported by the Intramural Research Program of the National Cancer
Institute, NIH.
NR 59
TC 38
Z9 38
U1 3
U2 32
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2012
VL 96
IS 2
BP 374
EP 381
DI 10.3945/ajcn.111.031328
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 978TW
UT WOS:000306769700020
PM 22695871
ER
PT J
AU Otto, MCD
Mozaffarian, D
Kromhout, D
Bertoni, AG
Sibley, CT
Jacobs, DR
Nettleton, JA
AF Otto, Marcia C. de Oliveira
Mozaffarian, Dariush
Kromhout, Doan
Bertoni, Alain G.
Sibley, Christopher T.
Jacobs, David R., Jr.
Nettleton, Jennifer A.
TI Dietary intake of saturated fat by food source and incident
cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; RISK-FACTORS; WOMENS HEALTH;
CHOLESTEROL; CONSUMPTION; MESA; HYPERTENSION; METAANALYSIS; PATTERNS
AB Background: Although dietary recommendations have focused on restricting saturated fat (SF) consumption to reduce cardiovascular disease (CVD) risk, evidence from prospective studies has not supported a strong link between total SF intake and CVD events. An understanding of whether food sources of SF influence these relations may provide new insights.
Objective: We investigated the association of SF consumption from different food sources and the incidence of CVD events in a multi-ethnic population.
Design: Participants who were 45-84 y old at baseline (n = 5209) were followed from 2000 to 2010. Diet was assessed by using a 120-item food-frequency questionnaire. CVD incidence (316 cases) was assessed during follow-up visits.
Results: After adjustment for demographics, lifestyle, and dietary confounders, a higher intake of dairy SF was associated with lower CVD risk [HR (95% CI) for +5 g/d and +5% of energy from dairy SF: 0.79 (0.68, 0.92) and 0.62 (0.47, 0.82), respectively]. In contrast, a higher intake of meat SF was associated with greater CVD risk [HR (95% CI) for +5 g/d and a +5% of energy from meat SF: 1.26 (1.02, 1.54) and 1.48 (0.98, 2.23), respectively]. The substitution of 2% of energy from meat SF with energy from dairy SF was associated with a 25% lower CVD risk [HR (95% CI): 0.75 (0.63, 0.91)]. No associations were observed between plant or butter SF and CVD risk, but ranges of intakes were narrow.
Conclusion: Associations of SF with health may depend on food-specific fatty acids or other nutrient constituents in foods that contain SF, in addition to SF. Am J Clin Nutr 2012;96:397-404.
C1 [Otto, Marcia C. de Oliveira; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Otto, Marcia C. de Oliveira; Nettleton, Jennifer A.] Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[Kromhout, Doan] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
[Bertoni, Alain G.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway.
RP Otto, MCD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg,Room 913, Boston, MA 02115 USA.
EM motto@hsph.harvard.edu
RI Sibley, Christopher/C-9900-2013; Kromhout, Daan/A-8566-2014
FU University of Texas Health Innovation for Cancer Prevention Research
Postdoctoral Fellowship, The University of Texas School of Public Health
- Cancer Prevention and Research Institute of Texas [RP101503]; NIH,
National Institute of Diabetes and Digestive and Kidney Diseases [K01,
5K0IDK082729-04]; National Heart, Lung, and Blood Institute
[N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166]
FX Supported by a University of Texas Health Innovation for Cancer
Prevention Research Postdoctoral Fellowship, The University of Texas
School of Public Health - Cancer Prevention and Research Institute of
Texas (grant RP101503; to MCOO); a K01 from the NIH, National Institute
of Diabetes and Digestive and Kidney Diseases (5K0IDK082729-04; to JAN);
and the National Heart, Lung, and Blood Institute (contracts
N01-HC-95159 through N01-HC-95166).
NR 41
TC 48
Z9 48
U1 13
U2 80
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2012
VL 96
IS 2
BP 397
EP 404
DI 10.3945/ajcn.112.037770
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 978TW
UT WOS:000306769700023
ER
PT J
AU Dorjgochoo, T
Gao, YT
Chow, WH
Shu, XO
Yang, G
Cai, QY
Rothman, N
Cai, H
Li, HL
Deng, XY
Franke, A
Roberts, LJ
Milne, G
Zheng, W
Dai, Q
AF Dorjgochoo, Tsogzolmaa
Gao, Yu-Tang
Chow, Wong-Ho
Shu, Xiao-ou
Yang, Gong
Cai, Qiuyin
Rothman, Nathaniel
Cai, Hui
Li, Honglan
Deng, Xinying
Franke, Adrian
Roberts, L. Jackson
Milne, Ginger
Zheng, Wei
Dai, Qi
TI Major metabolite of F-2-isoprostane in urine may be a more sensitive
biomarker of oxidative stress than isoprostane itself
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID SHANGHAI WOMENS HEALTH; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-E;
LIPID-PEROXIDATION; BREAST-CANCER; IN-VIVO; MOLECULAR-MECHANISMS;
BIOACTIVE PRODUCTS; HUMANS; RISK
AB Background: There is limited literature on the contributors to isoprostane metabolite 2,3-dinor-5,6-dihydro-15-F-2t-isoprostane (15-F-2t-IsoP-M) compared with F-2-isoprostanes (F-2-IsoPs) as an oxidative stress biomarker.
Objective: The objective of this study was to investigate whether plasma concentrations of antioxidants, urinary excretion rates of polyphenols, and antioxidants in food and dietary supplements are attributable to both urinary F-2-IsoP and 15-F-2t-IsoP-M concentrations.
Design: Dietary intake information and blood and urine samples were obtained from 845 healthy middle-aged and elderly female participants of the Shanghai Women's Health Study. Urinary isoprostanes (F-2-IsoPs and 15-F-2t-IsoP-M) were measured and adjusted for creatinine concentrations.
Results: Urinary 15-F-2t-IsoP-M and F-2-IsoP concentrations were lower in subjects who used a multivitamin. Lower F-2-IsoP concentrations were observed in ginseng users, whereas lower concentrations of 15-F-2t-IsoP-M were shown in subjects who used a vitamin E supplement. Plasma concentrations of several antioxidants (ie, beta-carotenes, both trans and cis beta-carotenes, lycopene other than trans, 5-cis and 7-cis isomers, cis anhydrolutein, and cis beta-cryptoxanthin) were inversely associated with 15-F-2t-IsoP-M but not with F-2-IsoPs, whereas beta-, gamma-, and delta-tocopherols were positively associated with 15-F-2t-IsoP-M but not with F-2-IsoPs. Urinary polyphenol quercetin was positively associated with both F-2-IsoPs and 15-F-2t-IsoP-M.
Conclusion: The results suggest that the F-2-IsoP major metabolite 15-F-2t-IsoP-M may be a more sensitive marker of endogenous oxidative stress status than are F-2-IsoPs in the assessment of effects of antioxidants on age-related diseases. Am J Clin Nutr 2012;96:405-14.
C1 [Dorjgochoo, Tsogzolmaa; Shu, Xiao-ou; Yang, Gong; Cai, Qiuyin; Cai, Hui; Deng, Xinying; Zheng, Wei; Dai, Qi] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA.
[Milne, Ginger] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Nashville, TN 37212 USA.
[Roberts, L. Jackson] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA.
[Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gao, Yu-Tang; Li, Honglan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Franke, Adrian] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
RP Dai, Q (reprint author), Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr, 2525 W End Ave,6th Floor,Suite 600, Nashville, TN 37203 USA.
EM qi.dai@vanderbilt.edu
RI Milne, Ginger/D-7648-2014
OI Milne, Ginger/0000-0003-3890-151X
FU NIH [R01CA106591, R01CA70867, N02 CP1101066]
FX Supported by the NIH (R01CA106591; to QD). In addition, the parent study
was supported by the NIH (R01CA70867; to WZ) and the NIH intramural
program (N02 CP1101066; to X-oS).
NR 45
TC 16
Z9 16
U1 2
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2012
VL 96
IS 2
BP 405
EP 414
DI 10.3945/ajcn.112.034918
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 978TW
UT WOS:000306769700024
PM 22760572
ER
PT J
AU Perna, FM
Oh, A
Chriqui, JF
Masse, LC
Atienza, AA
Nebeling, L
Agurs-Collins, T
Moser, RP
Dodd, KW
AF Perna, Frank M.
Oh, April
Chriqui, Jamie F.
Masse, Louise C.
Atienza, Audie A.
Nebeling, Linda
Agurs-Collins, Tanya
Moser, Richard P.
Dodd, Kevin W.
TI The Association of State Law to Physical Education Time Allocation in US
Public Schools
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CHILDHOOD; HEALTH; POLICY; INTERVENTIONS; TRACKING; IMPLEMENTATION;
OVERWEIGHT; ADULTHOOD; SYSTEM
AB Objectives. We examined whether public schools in states with specific and stringent physical education (PE) laws, as assessed by the Physical Education Related State Policy Classification System (PERSPCS), available on the Classification of Laws Associated with School Students (C.L.A.S.S.) Web site, reported more weekly PE time in the most recent School Health Policies and Programs Survey (SHPPS).
Methods. Schools (n = 410) were grouped by their state's PERSPCS time requirement scores (none, nonspecific requirement, or specific requirement). Average weekly school-level PE was calculated using the SHPPS-reported PE minutes. Weighted analyses determined if PE minutes/week differed by PERSPCS group.
Results. Schools in states with specific requirement laws averaged over 27 and 60 more PE minutes/week at the elementary and middle school levels, respectively, compared with schools within states with nonspecific laws and over 40 and 60 more PE minutes per week, respectively, compared with elementary and middle schools in states with no laws. High school results were nonsignificant.
Conclusions. Public health guidelines recommend at least 60 minutes of daily physical activity for children, and PE may further this goal. Strong codified law with specific time requirements for PE may be an important tool contributing toward adequate PE time and daily physical activity recommendations. (Am J Public Health. 2012;102:1594-1599. doi:10.2105/AJPH.2011.300587)
C1 [Perna, Frank M.; Atienza, Audie A.; Nebeling, Linda; Agurs-Collins, Tanya] NCI, Hlth Behav Res Branch, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA.
[Oh, April] NCI, Hlth Behav Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Chriqui, Jamie F.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA.
[Masse, Louise C.] Univ British Columbia, Dept Pediat, Vancouver, BC V6T 1W5, Canada.
[Masse, Louise C.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Moser, Richard P.] NCI, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Dodd, Kevin W.] NCI, Div Canc Prevent Biometry, Res Grp, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Perna, FM (reprint author), NCI, Hlth Behav Res Branch, Div Canc Control & Populat Sci, Behav Res Program, 6130 Execut Blvd,EPN 4074, Bethesda, MD 20892 USA.
EM pernafm@mail.nih.gov
FU National Cancer Institute [HHSN261201000350P, HHSP23320095645WC]
FX This work was partially supported by the National Cancer Institute by a
contract to the University of Illinois at Chicago Institute for Health
Research and Policy (HHSN261201000350P) and to the MayaTech Corporation
(HHSP23320095645WC)
NR 32
TC 14
Z9 14
U1 0
U2 6
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD AUG
PY 2012
VL 102
IS 8
BP 1594
EP 1599
DI 10.2105/AJPH.2011.300587
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 981AO
UT WOS:000306937900023
PM 22594746
ER
PT J
AU Center, DM
Schwartz, DA
Solway, J
Gail, D
Laposky, AD
Lin, QS
Gan, WN
AF Center, David M.
Schwartz, David A.
Solway, Julian
Gail, Dorothy
Laposky, Aaron D.
Lin, Qing S.
Gan, Weiniu
TI Genomic Medicine and Lung Diseases
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE molecular phenotypes; molecular networks; drug repurposing; epigenetics;
data sharing
ID IDIOPATHIC PULMONARY-FIBROSIS; TRANSLATIONAL MEDICINE; IDENTIFICATION;
INFLAMMATION; DISORDERS; KNOWLEDGE; ASTHMA; GENES
AB The recent explosion of genomic data and technology points to opportunities to redefine lung diseases at the molecular level; to apply integrated genomic approaches to elucidate mechanisms of lung pathophysiology; and to improve early detection, diagnosis, and treatment of lung diseases. Research is needed to translate genomic discoveries into clinical applications, such as detecting preclinical disease, predicting patient outcomes, guiding treatment choices, and most of all identifying potential therapeutic targets for lung diseases. The Division of Lung Diseases in the National Heart, Lung, and Blood Institute convened a workshop, "Genomic Medicine and Lung Diseases," to discuss the potential for integrated genomics and systems approaches to advance 21st century pulmonary medicine and to evaluate the most promising opportunities for this next phase of genomics research to yield clinical benefit. Workshop sessions included (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new technology and opportunity; (3) integrative genomics; (4) molecular anatomy of the lung; (5) novel data and information platforms; and (6) recommendations for exceptional research opportunities in lung genomics research.
C1 [Gail, Dorothy; Laposky, Aaron D.; Lin, Qing S.; Gan, Weiniu] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
[Center, David M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Schwartz, David A.] Univ Colorado Hosp, Dept Med, Aurora, CO USA.
[Solway, Julian] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
RP Gan, WN (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM ganw2@nhlbi.nih.gov
FU Division of Lung Diseases, National Heart, Lung, and Blood Institute,
National Institutes of Health
FX Supported by the Division of Lung Diseases, National Heart, Lung, and
Blood Institute, National Institutes of Health.
NR 26
TC 6
Z9 6
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 1
PY 2012
VL 186
IS 3
BP 280
EP 285
DI 10.1164/rccm.201203-0569WS
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 982JL
UT WOS:000307039200014
PM 22652029
ER
PT J
AU Nichols, LM
Masdeu, JC
Mattay, VS
Kohn, P
Emery, M
Sambataro, F
Kolachana, B
Elvevag, B
Kippenhan, S
Weinberger, DR
Berman, KF
AF Nichols, Lisa M.
Masdeu, Joseph C.
Mattay, Venkata S.
Kohn, Philip
Emery, Matthew
Sambataro, Fabio
Kolachana, Bhaskar
Elvevag, Brita
Kippenhan, Shane
Weinberger, Daniel R.
Berman, Karen F.
TI Interactive Effect of Apolipoprotein E Genotype and Age on Hippocampal
Activation During Memory Processing in Healthy Adults
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; TRAUMATIC BRAIN-INJURY; CEREBRAL-BLOOD-FLOW;
ALZHEIMERS-DISEASE; APOE GENOTYPE; GENETIC RISK; OLDER-ADULTS; NEURAL
ACTIVITY; E POLYMORPHISM; FMRI EVIDENCE
AB Context: Although the apolipoprotein E(APOE) epsilon 4 allele is a major genetic risk factor for late-onset Alzheimer disease, its effect on hippocampal function during episodic memory is controversial because studies have yielded mixed results. The age of the studied cohorts may contribute to this apparent inconsistency: activation for epsilon 4 carriers tends to be increased in studies of older adults but decreased in some studies of younger adults. Consistent with differential age effects, research in transgenic mice suggests that the epsilon 4 allele may particularly affect the aging process.
Objective: To define the interactions of age and this allelic variation on brain activation during episodic memory across adult life in healthy individuals.
Design: Functional magnetic resonance imaging (fMRI) using an episodic memory paradigm to test for differences in neuroactivation across APOE genotypes and age groups.
Setting: A federal research institute.
Participants: Healthy white volunteers (APOE epsilon 3 homozygotes and epsilon 2 and epsilon 4 heterozygotes) completed the fMRI task (133 volunteers aged 19-77 years).
Main Outcome Measure: Memory-related regional blood oxygenation level-dependent (BOLD) activation.
Results: Genotype affected the pattern of change in hippocampal BOLD activation across the adult lifespan: older age was associated with decreased activation in epsilon 2 carriers and, to a lesser extent, in epsilon 3 homozygotes, but this pattern was not observed in epsilon 4 carriers. Among young participants, epsilon 4 carriers had less hippocampal activation compared with epsilon 3 homozygotes despite similar task performance.
Conclusions: The findings support the hypothesis that aging and APOE allele status have interacting effects on the neural substrate of episodic memory and lend clarification to disparities in the literature. The stepwise decrease in activation with age found among genotype groups resembles the order of susceptibility to Alzheimer disease, suggesting a compensatory neurobiological mechanism in older asymptomatic epsilon 4 carriers.
C1 [Nichols, Lisa M.; Masdeu, Joseph C.; Mattay, Venkata S.; Kohn, Philip; Emery, Matthew; Sambataro, Fabio; Kolachana, Bhaskar; Elvevag, Brita; Kippenhan, Shane; Weinberger, Daniel R.; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA.
[Nichols, Lisa M.; Masdeu, Joseph C.; Kohn, Philip; Kippenhan, Shane; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA.
RP Berman, KF (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, 10 Ctr Dr,3C209, Bethesda, MD 20892 USA.
EM bermank@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010
OI Sambataro, Fabio/0000-0003-2102-416X
FU National Institute of Mental Health
FX This study was funded by the Intramural Research Program of the National
Institute of Mental Health.
NR 73
TC 18
Z9 19
U1 3
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD AUG
PY 2012
VL 69
IS 8
BP 804
EP 813
DI 10.1001/archgenpsychiatry.2011.1893
PG 10
WC Psychiatry
SC Psychiatry
GA 984JD
UT WOS:000307185000006
PM 22868934
ER
PT J
AU Hartz, SM
Short, SE
Saccone, NL
Culverhouse, R
Chen, LS
Schwantes-An, TH
Coon, H
Han, YH
Stephens, SH
Sun, JZ
Chen, XN
Ducci, F
Dueker, N
Franceschini, N
Frank, J
Geller, F
Guobjartsson, D
Hansel, NN
Jiang, CH
Keskitalo-Vuokko, K
Liu, Z
Lyytikainen, LP
Michel, M
Rawal, R
Hum, S
Rosenberger, A
Scheet, P
Shaffer, JR
Teumer, A
Thompson, JR
Vink, JM
Vogelzangs, N
Wenzlaff, AS
Wheeler, W
Xiao, XJ
Yang, BZ
Aggen, SH
Balmforth, AJ
Baumeister, SE
Beaty, T
Bennett, S
Bergen, AW
Boyd, HA
Broms, U
Campbell, H
Chatterjee, N
Chen, JC
Cheng, YC
Cichon, S
Couper, D
Cucca, F
Dick, DM
Foroud, T
Furberg, H
Giegling, I
Gu, FY
Hall, AS
Hallfors, J
Han, SZ
Hartmann, AM
Hayward, C
Heikkila, K
Hewitt, JK
Hottenga, JJ
Jensen, MK
Jousilahti, P
Kaakinen, M
Kittner, SJ
Konte, B
Korhonen, T
Landi, MT
Laatikainen, T
Leppert, M
Levy, SM
Mathias, RA
McNeil, DW
Medland, SE
Montgomery, GW
Muley, T
Murray, T
Nauck, M
North, K
Pergadia, M
Polasek, O
Ramos, EM
Ripatti, S
Risch, A
Ruczinski, I
Rudan, I
Salomaa, V
Schlessinger, D
Styrkarsdottir, U
Terracciano, A
Uda, M
Willemsen, G
Wu, XF
Abecasis, G
Barnes, K
Bickeboller, H
Boerwinkle, E
Boomsma, DI
Caporaso, N
Duan, JB
Edenberg, HJ
Francks, C
Gejman, PV
Gelernter, J
Grabe, HJ
Hops, H
Jarvelin, MR
Viikari, J
Kahonen, M
Kendler, KS
Lehtimaki, T
Levinson, DF
Marazita, ML
Marchini, J
Melbye, M
Mitchell, BD
Murray, JC
Nothen, MM
Penninx, BW
Raitakari, O
Rietschel, M
Rujescu, D
Samani, NJ
Sanders, AR
Schwartz, AG
Shete, S
Shi, JX
Spitz, M
Stefansson, K
Swan, GE
Thorgeirsson, T
Volzke, H
Wei, QY
Wichmann, HE
Amos, CI
Breslau, N
Cannon, DS
Ehringer, M
Grucza, R
Hatsukami, D
Heath, A
Johnson, EO
Kaprio, J
Madden, P
Martin, NG
Stevens, VL
Stitzel, JA
Weiss, RB
Kraft, P
Bierut, LJ
AF Hartz, Sarah M.
Short, Susan E.
Saccone, Nancy L.
Culverhouse, Robert
Chen, LiShiun
Schwantes-An, Tae-Hwi
Coon, Hilary
Han, Younghun
Stephens, Sarah H.
Sun, Juzhong
Chen, Xiangning
Ducci, Francesca
Dueker, Nicole
Franceschini, Nora
Frank, Josef
Geller, Frank
Guobjartsson, Daniel
Hansel, Nadia N.
Jiang, Chenhui
Keskitalo-Vuokko, Kaisu
Liu, Zhen
Lyytikainen, Leo-Pekka
Michel, Martha
Rawal, Rajesh
Hum, Sc
Rosenberger, Albert
Scheet, Paul
Shaffer, John R.
Teumer, Alexander
Thompson, John R.
Vink, Jacqueline M.
Vogelzangs, Nicole
Wenzlaff, Angela S.
Wheeler, William
Xiao, Xiangjun
Yang, Bao-Zhu
Aggen, Steven H.
Balmforth, Anthony J.
Baumeister, Sebastian E.
Beaty, Terri
Bennett, Siiri
Bergen, Andrew W.
Boyd, Heather A.
Broms, Ulla
Campbell, Harry
Chatterjee, Nilanjan
Chen, Jingchun
Cheng, Yu-Ching
Cichon, Sven
Couper, David
Cucca, Francesco
Dick, Danielle M.
Foroud, Tatiana
Furberg, Helena
Giegling, Ina
Gu, Fangyi
Hall, Alistair S.
Hallfors, Jenni
Han, Shizhong
Hartmann, Annette M.
Hayward, Caroline
Heikkila, Kauko
Hewitt, John K.
Hottenga, Jouke Jan
Jensen, Majken K.
Jousilahti, Pekka
Kaakinen, Marika
Kittner, Steven J.
Konte, Bettina
Korhonen, Tellervo
Landi, Maria-Teresa
Laatikainen, Tiina
Leppert, Mark
Levy, Steven M.
Mathias, Rasika A.
McNeil, Daniel W.
Medland, Sarah E.
Montgomery, Grant W.
Muley, Thomas
Murray, Tanda
Nauck, Matthias
North, Kari
Pergadia, Michele
Polasek, Ozren
Ramos, Erin M.
Ripatti, Samuli
Risch, Angela
Ruczinski, Ingo
Rudan, Igor
Salomaa, Veikko
Schlessinger, David
Styrkarsdottir, Unnur
Terracciano, Antonio
Uda, Manuela
Willemsen, Gonneke
Wu, Xifeng
Abecasis, Goncalo
Barnes, Kathleen
Bickeboeller, Heike
Boerwinkle, Eric
Boomsma, Dorret I.
Caporaso, Neil
Duan, Jubao
Edenberg, Howard J.
Francks, Clyde
Gejman, Pablo V.
Gelernter, Joel
Grabe, Hans Joergen
Hops, Hyman
Jarvelin, Marjo-Riitta
Viikari, Jorma
Kahonen, Mika
Kendler, Kenneth S.
Lehtimaki, Terho
Levinson, Douglas F.
Marazita, Mary L.
Marchini, Jonathan
Melbye, Mads
Mitchell, Braxton D.
Murray, Jeffrey C.
Nothen, Markus M.
Penninx, Brenda W.
Raitakari, Olli
Rietschel, Marcella
Rujescu, Dan
Samani, Nilesh J.
Sanders, Alan R.
Schwartz, Ann G.
Shete, Sanjay
Shi, Jianxin
Spitz, Margaret
Stefansson, Kari
Swan, Gary E.
Thorgeirsson, Thorgeir
Volzke, Henry
Wei, Qingyi
Wichmann, H. -Erich
Amos, Christopher I.
Breslau, Naomi
Cannon, Dale S.
Ehringer, Marissa
Grucza, Richard
Hatsukami, Dorothy
Heath, Andrew
Johnson, Eric O.
Kaprio, Jaakko
Madden, Pamela
Martin, Nicholas G.
Stevens, Victoria L.
Stitzel, Jerry A.
Weiss, Robert B.
Kraft, Peter
Bierut, Laura J.
TI Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset
Smokers
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Review
ID NICOTINIC RECEPTOR GENES; GENOME-WIDE ASSOCIATION; LUNG-CANCER;
SUSCEPTIBILITY LOCUS; HEAVY SMOKING; ADULT RATS; DEPENDENCE; ADOLESCENT;
INITIATION; RISK
AB Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.
Data Sources: Primary data.
Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.
DataExtraction: Uniform statistical analysis scripts were runlocally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD <= 10) with age-at-onset information, re-ducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset <= 16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with ther s16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.
Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01).
Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
C1 [Hartz, Sarah M.; Saccone, Nancy L.; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Pergadia, Michele; Grucza, Richard; Heath, Andrew; Madden, Pamela; Bierut, Laura J.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Short, Susan E.] Brown Univ, Providence, RI 02912 USA.
[Coon, Hilary; Leppert, Mark; Cannon, Dale S.; Weiss, Robert B.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Han, Younghun; Scheet, Paul; Xiao, Xiangjun; Wu, Xifeng; Shete, Sanjay; Spitz, Margaret; Wei, Qingyi; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Stephens, Sarah H.; Hewitt, John K.; Ehringer, Marissa; Stitzel, Jerry A.] Univ Colorado, Boulder, CO 80309 USA.
[Sun, Juzhong; Stevens, Victoria L.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Chen, Xiangning; Aggen, Steven H.; Chen, Jingchun; Dick, Danielle M.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Ducci, Francesca] St Georges Univ, Inst Psychiat Kings Coll, London, England.
[Ducci, Francesca] St Georges Univ, Dept Psychiat, London, England.
[Ducci, Francesca] Univ Pisa, Pisa, Italy.
[Dueker, Nicole; Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Franceschini, Nora; Couper, David; North, Kari] Univ N Carolina, Chapel Hill, NC USA.
[Geller, Frank; Rietschel, Marcella] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Geller, Frank; Boyd, Heather A.; Melbye, Mads] Statens Serum Inst, DK-2300 Copenhagen, Denmark.
[Guobjartsson, Daniel; Styrkarsdottir, Unnur; Stefansson, Kari; Thorgeirsson, Thorgeir] DeCODE Genet, Reykjavik, Iceland.
[Hansel, Nadia N.; Beaty, Terri; Mathias, Rasika A.; Murray, Tanda; Ruczinski, Ingo; Barnes, Kathleen] Johns Hopkins Univ, Baltimore, MD USA.
[Jiang, Chenhui; Yang, Bao-Zhu; Han, Shizhong; Gelernter, Joel] Yale Univ, Sch Med, New Haven, CT USA.
[Keskitalo-Vuokko, Kaisu; Broms, Ulla; Hallfors, Jenni; Heikkila, Kauko; Korhonen, Tellervo; Kaprio, Jaakko] Univ Helsinki, Hjelt Inst, Helsinki, Finland.
[Lyytikainen, Leo-Pekka; Kahonen, Mika; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Rosenberger, Albert; Bickeboeller, Heike] Univ Gottingen, Univ Med Ctr, Gottingen, Germany.
[Liu, Zhen; Marchini, Jonathan] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Michel, Martha; Bergen, Andrew W.; Swan, Gary E.] SRI Int, Menlo Pk, CA 94025 USA.
[Rawal, Rajesh; Wichmann, H. -Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Neuherberg, Germany.
[Shaffer, John R.; Marazita, Mary L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Teumer, Alexander; Baumeister, Sebastian E.; Nauck, Matthias; Grabe, Hans Joergen; Volzke, Henry] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
[Thompson, John R.; Samani, Nilesh J.] Univ Leicester, Leicester, Leics, England.
[Vink, Jacqueline M.; Hottenga, Jouke Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Vogelzangs, Nicole; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Wenzlaff, Angela S.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Wheeler, William] Information Management Serv Inc, Rockville, MD USA.
[Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, Leeds, W Yorkshire, England.
[Bennett, Siiri] Univ Washington, Seattle, WA 98195 USA.
[Campbell, Harry; Rudan, Igor] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Cichon, Sven] Forschungszentrum Julich, D-52425 Julich, Germany.
[Cichon, Sven; Nothen, Markus M.] Univ Bonn, Life & Brain Ctr, Bonn, Germany.
[Cichon, Sven; Nothen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Rome, Italy.
[Dick, Danielle M.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA.
[Foroud, Tatiana; Edenberg, Howard J.] Indiana Univ Sch Med, Indianapolis, IN USA.
[Furberg, Helena] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Giegling, Ina; Hartmann, Annette M.; Konte, Bettina; Rujescu, Dan] Univ Munich, Munich, Germany.
[Hayward, Caroline] Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Jensen, Majken K.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Broms, Ulla; Jousilahti, Pekka; Laatikainen, Tiina; Salomaa, Veikko; Kaprio, Jaakko] Natl Inst Hlth & Welf, Helsinki, Finland.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kittner, Steven J.] Baltimore Vet Adm Med Ctr, Baltimore, MD USA.
[Kittner, Steven J.] Univ Maryland, Baltimore, MD 21201 USA.
[Chatterjee, Nilanjan; Gu, Fangyi; Landi, Maria-Teresa; Caporaso, Neil; Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
[Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Schlessinger, David; Terracciano, Antonio] NIA, NIH, Bethesda, MD 20892 USA.
[Levy, Steven M.; Murray, Jeffrey C.] Univ Iowa, Iowa City, IA USA.
[McNeil, Daniel W.] W Virginia Univ, Morgantown, WV 26506 USA.
[Medland, Sarah E.; Montgomery, Grant W.; Martin, Nicholas G.] Queensland Inst Med Res, Herston, Qld 4006, Australia.
[Muley, Thomas] Univ Klinikum Heidelberg, Thoraxklin, Heidelberg, Germany.
[Polasek, Ozren] Univ Split, Sch Med, Split, Croatia.
[Ripatti, Samuli] Univ Helsinki, FIN-00014 Helsinki, Finland.
[Risch, Angela] DKFZ German Canc Res Ctr, Heidelberg, Germany.
[Uda, Manuela] Translat Lung Res Ctr Heidelberg, Heidelberg, Germany.
[Uda, Manuela] CNR, Rome, Italy.
[Abecasis, Goncalo] Univ Michigan, Ann Arbor, MI 48109 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ HealthSyst Res Inst, Evanston, IL USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Univ Chicago, Evanston, IL USA.
[Francks, Clyde] Max Planck Inst Psycholinguist, Nijmegen, Netherlands.
[Hops, Hyman] Oregon Res Inst, Eugene, OR 97403 USA.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, Sch Publ Hlth,MRC HPA Ctr Environm & Hlth, London SW7 2AZ, England.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland.
[Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, Inst Epidemiol 1, German Res Ctr Environm Hlth,Inst Med Informat Bi, D-80539 Munich, Germany.
[Breslau, Naomi] Michigan State Univ, E Lansing, MI 48824 USA.
[Hatsukami, Dorothy] Univ Minnesota, Minneapolis, MN USA.
[Johnson, Eric O.] RTI INt, Durham, NC USA.
[Hallfors, Jenni; Kaprio, Jaakko] Inst Mol Med Finland, Helsinki, Finland.
RP Bierut, LJ (reprint author), Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8134, St Louis, MO 63110 USA.
EM laura@wustl.edu
RI Lyytikainen, Leo-Pekka/C-8544-2016; Hayward, Caroline/M-8818-2016;
Risch, Angela/H-2669-2013; Gu, Fangyi/I-5957-2014; Rudan,
Igor/I-1467-2012; Breslau , Naomi/I-3196-2012; Ripatti,
Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Francks, Clyde/E-1384-2012; xiao,
xiangjun/B-1722-2013; Medland, Sarah/C-7630-2013; Abecasis,
Goncalo/B-7840-2010; terracciano, antonio/B-1884-2008; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014
OI Nothen, Markus/0000-0002-8770-2464; Hartz, Sarah/0000-0002-5429-3799;
Edenberg, Howard/0000-0003-0344-9690; Mitchell,
Braxton/0000-0003-4920-4744; Kaprio, Jaakko/0000-0002-3716-2455;
Thorgeirsson, Thorgeir/0000-0002-5149-7040; Martin,
Nicholas/0000-0003-4069-8020; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Hayward, Caroline/0000-0002-9405-9550;
Risch, Angela/0000-0002-8026-5505; Grucza, Richard/0000-0002-8191-6875;
Kaakinen, Marika/0000-0002-9228-0462; Abecasis,
Goncalo/0000-0003-1509-1825; Bergen, Andrew/0000-0002-1237-7644;
Korhonen, Tellervo/0000-0003-2838-3085; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Rudan, Igor/0000-0001-6993-6884;
Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Medland,
Sarah/0000-0003-1382-380X; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X
FU National Institutes of Health [R01HL089651-01, U01-DE018903,
N01-AG-1-2109, K01DA24758, N01-PC35145, N01-PC35146, N01-HR-46002, K07
CA118412, K02 AA018755, U10 AA008401, K01DA19498, K02DA021237, P01
CA089392, R01 MH59571, R01 MH61675, R01CA060691, U01 MH79469, U01
MH79470, R01 AA017535]; National Institutes of Health, National
Institute on Aging; University of California [7PT2000-2004]; Academy of
Finland [104781, 120315]; Center of Excellence in Complex Disease
Genetics; University Hospital Oulu; European Commission
[LSHM-CT-2004-005166, HEALTH-F4-2007-201413]; Academy of Finland Center
of Excellence in Complex Disease Genetics [129494]; Finnish Foundation
for Cardiovascular Diseases; Alfried Krupp von Bohlen und
Halbach-Stiftung; German Federal Ministry of Education and Research
[01ZZ9603, 01ZZ0103, 01ZZ0403]; NGNF-2; NGFNplus; IG MooDS [01GS08144,
01GS08147]; Dutch Scientific Organization(ZON-MW) [10-000-1002]; Center
for Molecular and Systems Biology; Genetic Association Information
Network of the Foundation for the US National Institutes of Health;
German Research Foundation (DFG) [GR 1912/5-1]; University of Helsinki
Biomedical Graduate School; Medical Research Fund of Tampere University
Hospital; National Institute for Health Research Academic Clinical
Fellowship at the Division of Mental Health, St George's, University of
London; NARSAD Young Investigator Award; Wellcome Trust; Paul Michael
Donovan Charitable Foundation; Andrew W. Mellon Foundation; Mary Beryl
Patch Turnbull Scholar Program; nih [R01 AA11330, R01 DA12690, R01
DA12849, R01DA026911, R01DA25888, R01NS45012, R21DA027070, T32 MH014677,
U01 HG004436, U01HG004438, U01 NS069208, U01HG004446, UL1RR024992]; N I
H [NIHDA12854, DA019951, R21DA033827, HHSN268200782096C, U01 HG004738,
U01DA02830, R01 MH67257, R01 MH59588, R01 MH59565, R01 MH59587, R01
MH60870, R01 MH59566, R01 MH59586, R01 MH60879, R01 MH81800, U01
MH46276, MH46289, MH46318, U54 RR020278, R01 DA017932, R01 DA03706]
FX This study was supported by grants R01HL089651-01, U01-DE018903,
N01-AG-1-2109, K01DA24758, N01-PC35145, N01-PC35146, N01-HR-46002, K07
CA118412, K02 AA018755, U10 AA008401, K01DA19498, K02DA021237, P01
CA089392, R01 MH59571, R01 MH61675, R01CA060691, R01CA060691, U01
MH79469, U01 MH79470, R01 AA017535, R01 AA11330, R01 DA12690, R01
DA12849, R01DA026911, R01DA25888, R01NS45012, R21DA027070, T32 MH014677,
U01 HG004436, U01HG004438, U01 NS069208, U01HG004446, UL1RR024992,
NIHDA12854, DA019951, R21DA033827, HHSN268200782096C, U01 HG004738,
U01DA02830, R01 MH67257, R01 MH59588, R01 MH59565, R01 MH59587, R01
MH60870, R01 MH59566, R01 MH59586, R01 MH60879, R01 MH81800, U01
MH46276, MH46289, MH46318, U54 RR020278, R01 DA017932, and R01 DA03706
from the National Institutes of Health; the Intramural Research Program
of the National Institutes of Health, National Institute on Aging; grant
7PT2000-2004 from the University of California Tobacco-Related Disease
Research Program; Academy of Finland (project grants 104781 and 120315
and the Center of Excellence in Complex Disease Genetics); University
Hospital Oulu; the European Commission; the European Commission's Sixth
Framework Program, Integrated Project GENADDICT (LSHM-CT-2004-005166),
and the Seventh Framework Program, Integrated Project ENGAGE
(HEALTH-F4-2007-201413); Academy of Finland Center of Excellence in
Complex Disease Genetics, Global Research Awards for Nicotine
Dependence; SALVE program grant 129494; The Finnish Foundation for
Cardiovascular Diseases; Alfried Krupp von Bohlen und Halbach-Stiftung;
German Federal Ministry of Education and Research grants 01ZZ9603,
01ZZ0103, 01ZZ0403, NGNF-2, NGFNplus, IG MooDS: 01GS08144, and
01GS08147; Geestkracht programme of the Dutch Scientific
Organization(ZON-MW grant 10-000-1002); matching funds from
participating institutes; Center for Molecular and Systems Biology; the
Genetic Association Information Network of the Foundation for the US
National Institutes of Health, German Research Foundation (DFG: GR
1912/5-1); University of Helsinki Biomedical Graduate School; Medical
Research Fund of Tampere University Hospital; National Institute for
Health Research Academic Clinical Fellowship at the Division of Mental
Health, St George's, University of London; NARSAD Young Investigator
Award; Wellcome Trust; The Paul Michael Donovan Charitable Foundation;
The Andrew W. Mellon Foundation; and The Mary Beryl Patch Turnbull
Scholar Program.
NR 40
TC 36
Z9 36
U1 5
U2 26
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD AUG
PY 2012
VL 69
IS 8
BP 854
EP 861
DI 10.1001/archgenpsychiatry.2012.124
PG 8
WC Psychiatry
SC Psychiatry
GA 984JD
UT WOS:000307185000011
PM 22868939
ER
PT J
AU Tobe, R
Yoo, MH
Fradejas, N
Carlson, BA
Calvo, S
Gladyshev, VN
Hatfield, DL
AF Tobe, Ryuta
Yoo, Min-Hyuk
Fradejas, Noelia
Carlson, Bradley A.
Calvo, Soledad
Gladyshev, Vadim N.
Hatfield, Dolph L.
TI Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer
cells via a thioredoxin-independent mechanism
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE cancer; glutathione; selenium cytotoxicity; selenoprotein; thioredoxin;
thioredoxin reductase 1
ID OXIDATIVE STRESS; HUMAN-DISEASE; SELENOPROTEINS; GLUTATHIONE;
PREVENTION; RESISTANT; APOPTOSIS; SYSTEM; TARGET; CYTOTOXICITY
AB Selenium is an essential trace element in mammals, but is toxic at high levels. It is best known for its cancer prevention activity, but cancer cells are more sensitive to selenite toxicity than normal cells. Since selenite treatment leads to oxidative stress, and the Trx (thioredoxin) system is a major antioxidative system, we examined the interplay between TR1 (Trx reductase 1) and Trx I deficiencies and selenite toxicity in DT cells, a malignant mouse cell line, and the corresponding parental NIH 3T3 cells. TR1-deficient cells were far more sensitive to selenite toxicity than Trx1-deficient or control cells. In contrast, this effect was not seen in cells treated with hydrogen peroxide, suggesting that the increased sensitivity of TR1 deficiency to selenite was not due to oxidative stress caused by this compound. Further analyses revealed that only TR1-deficient cells manifested strongly enhanced production and secretion of glutathione, which was associated with increased sensitivity of the cells to selenite. The results suggest a new role for TR1 in cancer that is independent of Trx reduction and compensated for by the glutathione system. The results also suggest that the enhanced selenite toxicity of cancer cells and simultaneous inhibition of TR1 can provide a new avenue for cancer therapy.
C1 [Tobe, Ryuta; Yoo, Min-Hyuk; Fradejas, Noelia; Carlson, Bradley A.; Hatfield, Dolph L.] NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA.
[Fradejas, Noelia; Calvo, Soledad] Univ Castilla La Mancha, Sch Med, Res Inst Neurol Incapac, Albacete 02006, Spain.
[Fradejas, Noelia; Calvo, Soledad] Univ Castilla La Mancha, Sch Med, Dept Med Sci, Albacete 02006, Spain.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.
RP Hatfield, DL (reprint author), NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM hatfield@mail.nih.gov
RI Gladyshev, Vadim/A-9894-2013
FU National Institutes of Health NCI Intramural Research Program; Center
for Cancer Research; National Institutes of Health [GM065204, CA080946];
Spanish Ministry of Sciences [BFU2006-14267]
FX This work was supported by the National Institutes of Health NCI
Intramural Research Program and the Center for Cancer Research (to
D.L.H.), by the National Institutes of Health [grant numbers GM065204
and CA080946 (to V.N.G.)], and by the Spanish Ministry of Sciences
[grant number BFU2006-14267 (to S.C.)].
NR 54
TC 10
Z9 11
U1 0
U2 7
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD AUG 1
PY 2012
VL 445
BP 423
EP 430
DI 10.1042/BJ20120618
PN 3
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982IN
UT WOS:000307036600014
PM 22594686
ER
PT J
AU Brinas, RP
Sundgren, A
Sahoo, P
Morey, S
Rittenhouse-Olson, K
Wilding, GE
Deng, W
Barchi, JJ
AF Brinas, Raymond P.
Sundgren, Andreas
Sahoo, Padmini
Morey, Susan
Rittenhouse-Olson, Kate
Wilding, Greg E.
Deng, Wei
Barchi, Joseph J., Jr.
TI Design and Synthesis of Multifunctional Gold Nanoparticles Bearing
Tumor-Associated Glycopeptide Antigens as Potential Cancer Vaccines
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID THOMSEN-FRIEDENREICH DISACCHARIDE; HUMORAL IMMUNE-RESPONSE; TANDEM
REPEAT SEQUENCE; EPITHELIAL MUCIN MUC4; T-CELL EPITOPE; CARBOHYDRATE
ANTIGEN; ANTIBODY-RESPONSES; PROSTATE-CANCER; IMMUNOLOGICAL EVALUATION;
ANTICANCER VACCINES
AB The development of vaccines against specific types of cancers will offer new modalities for therapeutic intervention. Here, we describe the synthesis of a novel vaccine construction prepared from spherical gold nanoparticles of 3-5 nm core diameters. The particles were coated with both the tumor associated glycopeptides antigens containing the cell surface mucin MUC4 with Thomsen Friedenreich (TF) antigen attached at different sites and a 28-residue peptide from the complement derived protein C3d to act as a B-cell activating "molecular adjuvant", The synthesis entailed solid phase glycopeptide synthesis, design of appropriate linkers, and attachment chemistry of the various molecules to the particles. Attachment to the gold surface was mediated by a novel thiol-containing 33 atom linker which was further modified to be included as a third "spacer" component in the synthesis of several three component vaccine platforms Groups of mice were vaccinated either with one of the nanoplatform constructs or with control particles without antigen coating. Evaluation of sera from the immunized animals in enzyme immunoassays (EIA) against each glycopeptide antigen showed a small but statistically significant immune response with production of both IgM and IgG isotypes. Vaccines with one carbohydrate antigen (B, C, and E) gave more robust responses than the one with two contiguous disaccharides (D), and vaccine E with a TF antigen attached to threonine at the 10th position of the peptide was selected for IgG over IgM suggesting isotype switching. The data suggested that this platform may be a viable delivery system for tumor-associated glycopeptide antigens.
C1 [Brinas, Raymond P.; Sundgren, Andreas; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Sahoo, Padmini; Morey, Susan; Rittenhouse-Olson, Kate] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA.
[Wilding, Greg E.; Deng, Wei] SUNY Buffalo, Dept Biostat, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA.
RP Barchi, JJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM Andreas.Sundgren@legemiddelverket.no; barchi@helix.nih.gov
RI Barchi Jr., Joseph/N-3784-2014;
OI Rittenhouse-Olson, Kate/0000-0001-8905-861X
FU Center for Cancer Research, National Cancer Institute
FX The authors wish to acknowledge Sergey Tarasov and Marzena Dyba of the
Biophysics Resource, Structural Biophysics Laboratory, Frederick
National Laboratories for Cancer Research for help in obtaining DLS
data, and Kunio Nagashima of the Electron Microscopy Laboratory,
Advanced Technology Program, Frederick National Laboratories for Cancer
Research for TEM images. The intramural Research Program of the Center
for Cancer Research, National Cancer Institute is acknowledged for
financial support.
NR 65
TC 47
Z9 48
U1 3
U2 58
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2012
VL 23
IS 8
BP 1513
EP 1523
DI 10.1021/bc200606s
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 988JU
UT WOS:000307487300003
PM 22812418
ER
PT J
AU Alexander, VM
Sano, K
Yu, ZQ
Nakajima, T
Choyke, PL
Ptaszek, M
Kobayashi, H
AF Alexander, Vinita M.
Sano, Kohei
Yu, Zhanqian
Nakajima, Takahito
Choyke, Peter L.
Ptaszek, Marcin
Kobayashi, Hisataka
TI Galactosyl Human Serum Albumin-NMP1 Conjugate: A Near Infrared
(NIR)-Activatable Fluorescence Imaging Agent to Detect Peritoneal
Ovarian Cancer Metastases
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID PROBES; GREEN
AB Patient survival depends on the completeness of resection of peritoneal ovarian cancer metastases (POCM), and therefore, it is important to develop methods to enhance detection. Previous probe designs based on activatable galactosyl human serum albumin (hGSA)-fluorophore pairs, which target lectin receptors expressed on POCM, have used only visible range dyes conjugated to hGSA. However, imaging probes emitting fluorescence in the NIR range are advantageous because NIR photons have deeper in vivo tissue penetration and result in lower background autofluorescence than those emitting in the visible range. A NIR-activatable hGSA fluorophore was synthesized using a bacteriochlorin-based dye, NMP1. NMP1 has two unique absorption peaks, one in the green range and the other in the NIR range, but emits at a NIR peak of 780 rim. NMP1, thus, has two different Stokes shifts that have the potential to allow imaging of POCM both at the peritoneal surface and just below it hGSA was conjugated with 2 NMP1 molecules to create a self quenching complex (hGSA-NMP1). The activation ratio of hGSA-NMP1 was measured by the. fluorescence intensity before and after exposure to 10% SDS. The activation ratio of hGSA-NMP1 was similar to 100 fold in vitro. Flow cytometry, fluorescence microscopy, and in vivo spectral fluorescence imaging were carried out to compare hGSA-NMP1 with hGSA-IR800 and hGSA-ICG (two always on control agents with similar emission to NMP1) in terms of comparative fluorescence signal and the ability to detect POCM in mice models. The sensitivity and specificity of hGSA-NMP1 for POCM implant detection were determined by colocalizing NMP1 emission spectra with red fluorescent protein (RFP) expressed constitutively in SHIN3 tumor implants at different depths below the peritoneal surface. In vitro, SHIN3 cells were easily detectable after 3 h of incubation with hGSA-NMP1. In vivo submillimeter POCM foci were clearly detectable with spectral fluorescence imaging using hGSA-NMP1. Among 555 peritoneal lesions, hGSA-NMP, using NIR and green excitation light, respectively, detect 75% of all lesions and 91% of lesions similar to 0.8 mm or greater in diameter. Few false positives were encountered. Nodules located at a depth below the small bowel surface were only depicted with hGSA-NMP1. We conclude that hGSA-NMP I is useful in imaging peritoneal ovarian cancer metastases, located both superficially and deep in the abdominal cavity.
C1 [Alexander, Vinita M.; Sano, Kohei; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yu, Zhanqian; Ptaszek, Marcin] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; University of
Maryland Baltimore County
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. M.P. thanks University of Maryland Baltimore County for
financial support (start-up funds and SRAIS award).
NR 24
TC 40
Z9 41
U1 6
U2 55
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2012
VL 23
IS 8
BP 1671
EP 1679
DI 10.1021/bc3002419
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 988JU
UT WOS:000307487300017
PM 22799539
ER
PT J
AU Yin, ZJ
Nguyen, HG
Chowdhury, S
Bentley, P
Bruckman, MA
Miermont, A
Gildersleeve, JC
Wang, Q
Huang, XF
AF Yin, Zhaojun
Huong Giang Nguyen
Chowdhury, Sudipa
Bentley, Philip
Bruckman, Michael A.
Miermont, Adeline
Gildersleeve, Jeffrey C.
Wang, Qian
Huang, Xuefei
TI Tobacco Mosaic Virus as a New Carrier for Tumor Associated Carbohydrate
Antigens
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID KEYHOLE LIMPET HEMOCYANIN; TN ANTIGEN; B-CELL; ANTICANCER VACCINES;
SURFACE MODIFICATION; ANTIBODY-RESPONSES; BREAST-CARCINOMA; CANCER;
EPITOPE; EXPRESSION
AB Tumor-associated carbohydrate antigens (TACAs) are being actively studied as targets for antitumor vaccine development. One serious challenge was the low immuno-genecity of these antigens. Herein, we report the results of using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without, resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities toward Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.
C1 [Huong Giang Nguyen; Bruckman, Michael A.; Wang, Qian] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA.
[Yin, Zhaojun; Bentley, Philip; Miermont, Adeline; Huang, Xuefei] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.
[Chowdhury, Sudipa; Gildersleeve, Jeffrey C.] NCI, Chem Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Wang, Q (reprint author), Univ S Carolina, Dept Chem & Biochem, 631 Sumter St, Columbia, SC 29208 USA.
EM wang263@mailbox.sc.edu; xuefei@chemistry.msu.edu
RI Wang, Qian/J-2144-2012; Yin, Zhaojun/F-7376-2013; Gildersleeve,
Jeffrey/N-3392-2014; Huang, Xuefei/G-3371-2014;
OI Yin, Zhaojun/0000-0003-4396-0215; Huang, Xuefei/0000-0002-6468-5526;
Wang, Qian/0000-0002-2149-384X
FU National Cancer Institute [R01CA149451-01A1]; NSF [CHE-0748690]; Alfred
P. Sloan Scholarship; Camille Dreyfus Teacher Scholar Award; NIH, NCI
FX The authors are indebted to Professor J. Culver (University of Maryland)
for providing the mutant virus TMV1cys. We would like to thank the
National Cancer Institute for generous financial support of our work
(XH, R01CA149451-01A1), partial financial support from NSF (QW,
CHE-0748690), the Alfred P. Sloan Scholarship (QW), and the Camille
Dreyfus Teacher Scholar Award (QW). This work was supported in part by
the intramural research program of the NIH, NCI.
NR 58
TC 35
Z9 37
U1 5
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2012
VL 23
IS 8
BP 1694
EP 1703
DI 10.1021/bc300244a
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 988JU
UT WOS:000307487300020
PM 22812480
ER
PT J
AU Sarsour, EH
Kalen, AL
Xiao, Z
Veenstra, TD
Chaudhuri, L
Venkataraman, S
Reigan, P
Buettner, GR
Goswami, PC
AF Sarsour, Ehab H.
Kalen, Amanda L.
Xiao, Zhen
Veenstra, Timothy D.
Chaudhuri, Leena
Venkataraman, Sujatha
Reigan, Philip
Buettner, Garry R.
Goswami, Prabhat C.
TI Manganese Superoxide Dismutase Regulates a Metabolic Switch during the
Mammalian Cell Cycle
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN FIBROBLASTS; OXIDATIVE STRESS; EPITHELIAL-CELLS; CANCER CELLS; S
PHASE; GROWTH; OVEREXPRESSION; GLYCOLYSIS; MNSOD; ACCUMULATION
AB Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment. This study investigates the hypothesis that manganese superoxide dismutase (MnSOD) regulates cellular redox flux and glucose consumption during the cell cycle. A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts, which was absent in MnSOD homozygous knockout fibroblasts. Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells, which was associated with an increase in glucose and oxygen consumption, and a decrease in MnSOD activity. Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine (68, 89, 122, and 202) and arginine (197 and 216) residues. MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD. Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site. Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide, a negatively charged substrate. These results support the hypothesis that MnSOD regulates a "metabolic switch" during progression from quiescent through the proliferative cycle. We propose MnSOD as a new molecular player contributing to the Warburg effect. Cancer Res; 72(15); 3807-16. (C) 2012 AACR.
C1 [Sarsour, Ehab H.; Kalen, Amanda L.; Buettner, Garry R.; Goswami, Prabhat C.] Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Div, Iowa City, IA 52242 USA.
[Xiao, Zhen; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Frederick, MD 21701 USA.
[Chaudhuri, Leena] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ USA.
[Venkataraman, Sujatha] Univ Colorado, Dept Pediat, Denver, CO 80202 USA.
[Reigan, Philip] Univ Colorado, Sch Pharm, Denver, CO USA.
RP Goswami, PC (reprint author), Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Div, Iowa City, IA 52242 USA.
EM prabhat-goswami@uiowa.edu
OI Buettner, Garry/0000-0002-5594-1903
FU NIH [CA111365]; NIEHS [P42 ES 013661]; NCI [HHSN261200800001E]
FX This work is supported by NIH CA111365 and NIEHS P42 ES 013661. The mass
spectrometry efforts of this project have been funded in whole or in
part with NCI Contract HHSN261200800001E.
NR 41
TC 25
Z9 27
U1 0
U2 13
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 AUG 1
PY 2012
VL 72
IS 15
BP 3807
EP 3816
DI 10.1158/0008-5472.CAN-11-1063
PG 10
WC Oncology
SC Oncology
GA 986PC
UT WOS:000307354100012
PM 22710435
ER
PT J
AU Stevens, WD
Kahn, I
Wig, GS
Schacter, DL
AF Stevens, W. Dale
Kahn, Itamar
Wig, Gagan S.
Schacter, Daniel L.
TI Hemispheric Asymmetry of Visual Scene Processing in the Human Brain:
Evidence from Repetition Priming and Intrinsic Activity
SO CEREBRAL CORTEX
LA English
DT Article
DE conceptual; laterality; parahippocampal place area; repetition
suppression; resting-state functional connectivity
ID STATE FUNCTIONAL CONNECTIVITY; EVENT-RELATED FMRI; HUMAN PARAHIPPOCAMPAL
CORTEX; LATERAL OCCIPITAL COMPLEX; RIGHT CEREBRAL HEMISPHERE; DEFAULT
MODE NETWORK; RESTING HUMAN BRAIN; EXPLICIT MEMORY; STRUCTURAL
CONNECTIVITY; ATTENTIONAL MODULATION
AB Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.
C1 [Stevens, W. Dale; Wig, Gagan S.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Stevens, W. Dale; Kahn, Itamar; Wig, Gagan S.; Schacter, Daniel L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Kahn, Itamar] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Wig, Gagan S.] Washington Univ, Dept Neurol, Sch Med, St Louis, MO 63104 USA.
RP Stevens, WD (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-101, Bethesda, MD 20892 USA.
EM william.stevens@nih.gov
OI Schacter, Daniel/0000-0002-2460-6061
FU National Institutes of Health [MH060941]
FX National Institutes of Health grant (MH060941 to D.L.S.).
NR 120
TC 19
Z9 19
U1 10
U2 30
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 AUG
PY 2012
VL 22
IS 8
BP 1935
EP 1949
DI 10.1093/cercor/bhr273
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 988JI
UT WOS:000307486100020
PM 21968568
ER
PT J
AU Chun, JH
Pike, VW
AF Chun, Joong-Hyun
Pike, Victor W.
TI Single-Step Radiosynthesis of "18F-Labeled Click Synthons" from
Azide-Functionalized Diaryliodonium Salts
SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
DE Click chemistry; Hypervalent compounds; Imaging agents; Isotopic
labeling; Radiochemistry
ID POSITRON-EMISSION-TOMOGRAPHY; CHEMISTRY; F-18; PET; RADIOFLUORINATION;
DERIVATIVES; RADIOLABELS; TOSYLATES; ROUTE; ION
AB Positron emission tomography (PET) is an increasingly important biomedical imaging technique that relies on the development of radiotracers labeled with positron emitters to achieve biochemical specificity. Fluorine-18 (t1/2 = 109.7 min) is an attractive positron-emitting radiolabel for organic radiotracers, primarily because of its longer half-life and greater availability relative to those of the main alternative, carbon-11 (t1/2 = 20.4 min). Rapid, simple methods are sought for labeling prospective PET radiotracers with fluorine-18 from cyclotron-produced aqueous [18F]fluoride ion, which must often be converted first into a suitably reactive labeling synthon for use in a subsequent labeling reaction. The use of 18F-labeled synthons in click chemistry is attracting increasing attention for labeling PET radiotracers. Herein we describe rapid, single-step radiosynthesis of azido- or azidomethyl-bearing [18F]fluoroarenes from the reactions of diaryliodonium salts with no-carrier-added [18F]fluoride ion within a microfluidic apparatus to provide previously poorly accessible 18F-labeled click synthons in radiochemical yields of 15?% for 4-[18F]fluorophenyl azide and about 40?% for each of the [18F](azidomethyl)fluorobenzenes. The radiosynthesis of the latter synthons was possible under wet conditions, so obviating the need to dry the cyclotron-produced [18F]fluoride ion and greatly enhancing the practicality of the method.
C1 [Chun, Joong-Hyun; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3 C346A, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIMH)
FX We thank the Intramural Research Program of the National Institutes of
Health (NIMH) for the support of this research and are grateful to the
NIH Clinical PET department (Chief, Dr. P. Herscovitch) for production
of fluorine-18.
NR 37
TC 20
Z9 20
U1 2
U2 33
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1434-193X
J9 EUR J ORG CHEM
JI Eur. J. Org. Chem.
PD AUG
PY 2012
IS 24
BP 4541
EP 4547
DI 10.1002/ejoc.201200695
PG 7
WC Chemistry, Organic
SC Chemistry
GA 988NK
UT WOS:000307497600012
ER
PT J
AU Wellons, MF
Fujimoto, VY
Baker, VL
Barrington, DS
Broomfield, D
Catherino, WH
Richard-Davis, G
Ryan, M
Thornton, K
Armstrong, AY
AF Wellons, Melissa F.
Fujimoto, Victor Y.
Baker, Valerie L.
Barrington, Debbie S.
Broomfield, Diana
Catherino, William H.
Richard-Davis, Gloria
Ryan, Mary
Thornton, Kim
Armstrong, Alicia Y.
TI Race matters: a systematic review of racial/ethnic disparity in Society
for Assisted Reproductive Technology reported outcomes
SO FERTILITY AND STERILITY
LA English
DT Review
DE Race; ethnicity; disparity; IVF; SART
ID WHITE WOMEN; PREGNANCY; ETHNICITY; ACCESS
AB Objective: To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications.
Design: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS.
Setting: Not applicable.
Patient(s): Not applicable.
Intervention(s): In vitro fertilization cycles reported to SART.
Main Outcome Measure(s): Any outcomes reported in SART CORS.
Result(s): Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data.
Conclusion(s): Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles. (Fertil Steril (R) 2012;98:406-9. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Wellons, Melissa F.] Univ Alabama Birmingham, Div Reprod Endocrinol & Infertil, Birmingham, AL 35249 USA.
[Fujimoto, Victor Y.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
[Baker, Valerie L.] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA.
[Barrington, Debbie S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Barrington, Debbie S.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA.
[Broomfield, Diana] Maryland IVF, Columbia, MD USA.
[Broomfield, Diana] Howard Univ, Coll Med, Dept Obstet & Gynecol, Washington, DC USA.
[Catherino, William H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Richard-Davis, Gloria] Meharry Med Coll, Dept Obstet & Gynecol, Nashville, TN 37208 USA.
[Ryan, Mary] NIH Lib, Bethesda, MD USA.
[Thornton, Kim] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02215 USA.
[Thornton, Kim] Boston IVF, Waltham, MA USA.
[Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Wellons, MF (reprint author), Univ Alabama Birmingham, Div Reprod Endocrinol & Infertil, 10390 Women & Infants Ctr,1700 6th Ave S, Birmingham, AL 35249 USA.
EM wello002@uab.edu
FU EMD Serono; Ferring Pharmaceuticals; National Institutes of
Health/National Heart, Lung, and Blood Institute [K23-HL-87114];
National Institutes of Health
FX W.H.C. receives relevant grant support from EMD Serono and Ferring
Pharmaceuticals. M. F. W. has nothing to disclose. V.Y.F. has nothing to
disclose. V. L. B. has nothing to disclose. D. S. B. has nothing to
disclose. D. B. has nothing to disclose. G.R.-D. has nothing to
disclose. M. R. has nothing to disclose. K. T. has nothing to disclose.
A.Y.A. has nothing to disclose.; M.F.W. is supported by a grant
(K23-HL-87114) from the National Institutes of Health/National Heart,
Lung, and Blood Institute. M. F. W. and V.Y.F. received National
Institutes of Health-sponsored travel funds for a meeting regarding this
work.
NR 18
TC 26
Z9 26
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD AUG
PY 2012
VL 98
IS 2
BP 406
EP 409
DI 10.1016/j.fertnstert.2012.05.012
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 981NP
UT WOS:000306975400026
PM 22698638
ER
PT J
AU Lynch, CD
Sundaram, R
Louis, GMB
Lum, KJ
Pyper, C
AF Lynch, Courtney D.
Sundaram, Rajeshwari
Louis, Germaine M. Buck
Lum, Kirsten J.
Pyper, Cecilia
TI Are increased levels of self-reported psychosocial stress, anxiety, and
depression associated with fecundity?
SO FERTILITY AND STERILITY
LA English
DT Article
DE Fertility; stress; anxiety; depression; social support
ID CONCEPTION PROBABILITIES; PERCEIVED STRESS; MENSTRUAL-CYCLE; INFERTILE
WOMEN; PREGNANCY RATES; SOCIAL SUPPORT; FERTILITY; DISTRESS; ADOPTION;
METAANALYSIS
AB Objective: To assess the association between self-reported measures of stress, anxiety, depression, and related constructs and fecundity.
Design: Prospective cohort study of women trying to conceive.
Setting: United Kingdom.
Patient(s): Three hundred thirty-nine women aged 18-40 years who were attempting to conceive.
Intervention(s): Completed daily diaries for up to six cycles or until pregnancy was detected. For each cycle, stress biomarkers were measured and psychosocial questionnaires were completed.
Main Outcome Measures(s): Fecundability odds ratios (FORs) and 95% confidence intervals were calculated using discrete time survival methods, and the day-specific probabilities of pregnancy were calculated using Bayesian statistical techniques.
Result(s): Among the 339 women, 207 (61%) became pregnant during the study, 69 (20%) did not become pregnant, and 63 (19%) withdrew. After controlling for maternal age, parity, months trying to conceive before enrollment, smoking, caffeine use, and frequency of intercourse, we found no association between most psychosocial measures and FORs or the day-specific probabilities of pregnancy save for an increased FOR for women reporting higher versus lower levels of social support.
Conclusion(s): Self-reported psychosocial stress, anxiety, and depression were not associated with fecundity. Any adverse effect of stress or psychological disturbance on fecundity does not appear to be detectable via the questionnaires administered. (Fertil Steril (R) 2012;98:453-8. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Lynch, Courtney D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Sundaram, Rajeshwari; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Lum, Kirsten J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Pyper, Cecilia] Univ Oxford, Natl Perinatal Epidemiol Unit, Oxford OX1 2JD, England.
RP Lynch, CD (reprint author), Ohio State Univ, Coll Med, Dept Obstet & Gynecol, 395 W 12th Ave,Room 580, Columbus, OH 43210 USA.
EM Courtney.Lynch@osumc.edu
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; UK National Health Service Executive Primary Care Career
Scientist and Service Research and Development Awards; DLM Charitable
Trust
FX Supported in part by the intramural program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(partial support of data collection, analysis of biomarker data, and
statistical analysis); the UK National Health Service Executive Primary
Care Career Scientist and Service Research and Development Awards (to C.
P.); the DLM Charitable Trust (Oxford Conception Study staff salaries);
and SPD Development Company Limited (formerly Unipath, which provided
fertility monitors, pregnancy tests, and related technical assistance
for devices).
NR 35
TC 16
Z9 16
U1 3
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD AUG
PY 2012
VL 98
IS 2
BP 453
EP 458
DI 10.1016/j.fertnstert.2012.05.018
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 981NP
UT WOS:000306975400034
PM 22698634
ER
PT J
AU Langan, RC
Holzman, K
Coblentz, M
AF Langan, R. C.
Holzman, K.
Coblentz, M.
TI Strangulated hernia through a defect in the broad ligament: a sheep in
wolf's clothing
SO HERNIA
LA English
DT Article
DE Internal hernia; Small bowel obstruction; Broad ligament; De novo bowel
obstruction
AB Small bowel obstruction due to an internal hernia is an uncommon finding and, when caused by a defect in the broad ligament, it is exceptionally rare. This condition should be considered when evaluating all female patients presenting with de novo small bowel obstruction. We report an unusual case of intestinal obstruction from an internal hernia through the left broad ligament in a middle-aged patient with no prior surgical history and discuss the relevant literature and treatment. Although an oncologic diagnosis should be entertained, a small bowel obstruction arising in the pelvis may involve the broad ligament in parous patients. An internal hernia through the broad ligament should be considered in the differential diagnoses of female patients presenting with intestinal obstruction.
C1 [Langan, R. C.] NCI, NIH, Bethesda, MD 20892 USA.
[Langan, R. C.; Holzman, K.; Coblentz, M.] St Barnabas Hosp, Dept Surg, Livingston, NJ 07039 USA.
RP Langan, RC (reprint author), NCI, NIH, 10 Ctr Dr,CRC 3-3940, Bethesda, MD 20892 USA.
EM Russell.Langan@gmail.com
NR 4
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1265-4906
J9 HERNIA
JI Hernia
PD AUG
PY 2012
VL 16
IS 4
BP 481
EP 483
DI 10.1007/s10029-010-0761-1
PG 3
WC Surgery
SC Surgery
GA 986IL
UT WOS:000307335200019
PM 21153560
ER
PT J
AU Chastin, SFM
Gardiner, P
Matthews, C
Stamatakis, E
Grant, M
Deforche, B
Owen, N
AF Chastin, S. F. M.
Gardiner, P.
Matthews, C.
Stamatakis, E.
Grant, M.
Deforche, B.
Owen, N.
TI SEDENTARY BEHAVIOUR: OPPORTUNITIES FOR ACTION SYMPOSIUM
SO JOURNAL OF AGING AND PHYSICAL ACTIVITY
LA English
DT Meeting Abstract
DE Sedentary Behaviour; Intervention; Behaviour Change
C1 [Chastin, S. F. M.; Grant, M.] Glasgow Caledonian Univ, Glasgow G4 0BA, Lanark, Scotland.
[Gardiner, P.; Owen, N.] Univ Queensland, Brisbane, Qld 4072, Australia.
[Matthews, C.] NCI, Bethesda, MD 20892 USA.
[Stamatakis, E.] UCL, London WC1E 6BT, England.
[Deforche, B.] Vrije Univ Brussel, Brussels, Belgium.
[Deforche, B.] Univ Ghent, Ghent, Belgium.
RI Gardiner, Paul/F-2751-2010; Owen, Neville/K-5986-2012
OI Gardiner, Paul/0000-0002-8072-2673;
NR 0
TC 0
Z9 0
U1 1
U2 4
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1063-8652
J9 J AGING PHYS ACTIV
JI J. Aging Phys. Act.
PD AUG
PY 2012
VL 20
SU S
BP S300
EP S300
PG 1
WC Geriatrics & Gerontology; Gerontology; Sport Sciences
SC Geriatrics & Gerontology; Sport Sciences
GA 987QZ
UT WOS:000307433500519
ER
PT J
AU Gudlaugsson, J
Gudnason, V
Aspelund, T
Siggeirsdottir, K
Johannsson, E
Arngrimsson, SA
Harris, TB
Jonsson, PV
Olafsdottir, AS
AF Gudlaugsson, Janus
Gudnason, Vilmundur
Aspelund, Thor
Siggeirsdottir, Kristin
Johannsson, Erlingur
Arngrimsson, Sigurbjorn A.
Harris, Tamara B.
Jonsson, Palmi, V
Olafsdottir, Anna S.
TI EFFECTS OF A 6-MONTH MULTIMODAL TRAINING INTERVENTION ON RETENTION OF
FUNCTIONAL FITNESS IN OLDER ADULTS: A RANDOMIZED-CONTROLLED CROSS-OVER
DESIGN
SO JOURNAL OF AGING AND PHYSICAL ACTIVITY
LA English
DT Meeting Abstract
DE Fitness; Disability; Physical Performance; Exercise
C1 [Gudlaugsson, Janus; Johannsson, Erlingur; Arngrimsson, Sigurbjorn A.; Olafsdottir, Anna S.] Univ Iceland, IS-101 Reykjavik, Iceland.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RI Olafsdottir, Anna/A-8804-2013; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Olafsdottir, Anna/0000-0002-7258-1727; Aspelund,
Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 6
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1063-8652
J9 J AGING PHYS ACTIV
JI J. Aging Phys. Act.
PD AUG
PY 2012
VL 20
SU S
BP S89
EP S89
PG 1
WC Geriatrics & Gerontology; Gerontology; Sport Sciences
SC Geriatrics & Gerontology; Sport Sciences
GA 987QZ
UT WOS:000307433500150
ER
PT J
AU Matthews, CE
AF Matthews, Charles E.
TI Sedentary behavior and health: A view from the National Institutes of
Health-American Association of Retired Persons diet and health study
SO JOURNAL OF AGING AND PHYSICAL ACTIVITY
LA English
DT Meeting Abstract
C1 [Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1063-8652
J9 J AGING PHYS ACTIV
JI J. Aging Phys. Act.
PD AUG
PY 2012
VL 20
SU S
BP S300
EP S301
PG 2
WC Geriatrics & Gerontology; Gerontology; Sport Sciences
SC Geriatrics & Gerontology; Sport Sciences
GA 987QZ
UT WOS:000307433500520
ER
PT J
AU Kostka, JE
Green, SJ
Rishishwar, L
Prakash, O
Katz, LS
Marino-Ramirez, L
Jordan, IK
Munk, C
Ivanova, N
Mikhailova, N
Watson, DB
Brown, SD
Palumbo, AV
Brooks, SC
AF Kostka, Joel E.
Green, Stefan J.
Rishishwar, Lavanya
Prakash, Om
Katz, Lee S.
Marino-Ramirez, Leonardo
King Jordan, I.
Munk, Christine
Ivanova, Natalia
Mikhailova, Natalia
Watson, David B.
Brown, Steven D.
Palumbo, Anthony V.
Brooks, Scott C.
TI Genome Sequences for Six Rhodanobacter Strains, Isolated from Soils and
the Terrestrial Subsurface, with Variable Denitrification Capabilities
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID SP NOV.; GAMMAPROTEOBACTERIUM; GINSENG
AB We report the first genome sequences for six strains of Rhodanobacter species isolated from a variety of soil and subsurface environments. Three of these strains are capable of complete denitrification and three others are not. However, all six strains contain most of the genes required for the respiration of nitrate to gaseous nitrogen. The nondenitrifying members of the genus lack only the gene for nitrate reduction, the first step in the full denitrification pathway. The data suggest that the environmental role of bacteria from the genus Rhodanobacter should be reevaluated.
C1 [Kostka, Joel E.; Rishishwar, Lavanya; King Jordan, I.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
[Green, Stefan J.] Univ Illinois, Res Resource Ctr, DNA Serv Facil, Chicago, IL USA.
[Prakash, Om] Natl Ctr Cell Sci, Pune, Maharashtra, India.
[Marino-Ramirez, Leonardo] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Katz, Lee S.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Kostka, Joel E.; Marino-Ramirez, Leonardo; King Jordan, I.] PanAmer Bioinformat Inst, Santa Marta, Magdalena, Colombia.
[Munk, Christine; Ivanova, Natalia; Mikhailova, Natalia] US DOE, Joint Genome Inst, Walnut Creek, CA USA.
[Watson, David B.; Brooks, Scott C.] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA.
[Brown, Steven D.; Palumbo, Anthony V.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN USA.
RP Kostka, JE (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
EM joel.kostka@biology.gatech.edu
RI Palumbo, Anthony/A-4764-2011; Marino-Ramirez, Leonardo/I-5759-2013;
Brooks, Scott/B-9439-2012; Brown, Steven/A-6792-2011;
OI Palumbo, Anthony/0000-0002-1102-3975; Rishishwar,
Lavanya/0000-0002-2055-9392; Marino-Ramirez,
Leonardo/0000-0002-5716-8512; Brooks, Scott/0000-0002-8437-9788; Brown,
Steven/0000-0002-9281-3898; Green, Stefan/0000-0003-2781-359X
FU Office of Science (BER), U.S. Department of Energy [DE-FG02-07ER64373,
-97ER62469, -97ER64398]; Oak Ridge Integrated Field-Research Challenge;
U.S. Department of Energy [DE-AC05-00OR22725]; Intramural Research
Program of the NIH, NLM, NCBI; Office of Science of the U.S. Department
of Energy [DE-AC02-05CH11231]
FX This research was supported by the Office of Science (BER), U.S.
Department of Energy, grant numbers DE-FG02-07ER64373, -97ER62469, and
-97ER64398 and by the Oak Ridge Integrated Field-Research Challenge,
operated by the Environmental Sciences Division, Oak Ridge National
Laboratory (ORNL).; ORNL is managed by UT-Battelle, LLC, for the U.S.
Department of Energy contract no. DE-AC05-00OR22725.; This research was
supported in part by the Intramural Research Program of the NIH, NLM,
NCBI.; The complete genome of Rhodanobacter denitrificans strain 2APBS1
was sequenced by the U.S. Department of Energy Joint Genome Institute,
supported by the Office of Science of the U.S. Department of Energy
under contract no. DE-AC02-05CH11231.
NR 17
TC 15
Z9 15
U1 2
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD AUG
PY 2012
VL 194
IS 16
BP 4461
EP 4462
DI 10.1128/JB.00871-12
PG 2
WC Microbiology
SC Microbiology
GA 984NQ
UT WOS:000307198100048
PM 22843592
ER
PT J
AU Mentz, RJ
Schulte, PJ
Kitzman, DW
Fiuzat, M
Kraus, WE
Pina, IL
Keteyian, SJ
Fleg, JL
Ellis, SJ
Whellan, DJ
O'Connor, CM
AF Mentz, R. J.
Schulte, P. J.
Kitzman, D. W.
Fiuzat, M.
Kraus, W. E.
Pina, I. L.
Keteyian, S. J.
Fleg, J. L.
Ellis, S. J.
Whellan, D. J.
O'Connor, C. M.
TI Beta-Blocker Selectivity in Heart Failure (HF) Patients With Chronic
Obstructive Pulmonary Disease (COPD): Insights from HF-A Controlled
Trial Investigating Outcomes of Exercise Training (HF-ACTION)
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Meeting Abstract
CT 16th Annual Scientific Meeting of the Heart-Failure-Society-of-America
CY SEP 09-12, 2012
CL Seattle, WA
SP Heart Failure Soc Amer
C1 [Mentz, R. J.; Schulte, P. J.; Fiuzat, M.; Kraus, W. E.; Ellis, S. J.; O'Connor, C. M.] Duke Univ, DCRI, Durham, NC USA.
[Kitzman, D. W.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Pina, I. L.] Montefiore Med Ctr, New York, NY USA.
[Keteyian, S. J.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Fleg, J. L.] NHLBI, Bethesda, MD 20892 USA.
[Whellan, D. J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD AUG
PY 2012
VL 18
IS 8
SU 1
MA 203
BP S63
EP S63
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 991CS
UT WOS:000307679700204
ER
PT J
AU Cai, LS
Liow, JS
Morse, C
Innis, R
Pike, V
AF Cai, Lisheng
Liow, Jeih-San
Morse, Cheryl
Innis, Robert
Pike, Victor
TI Development of candidate F-18-labeled PET imaging agents for
beta-amyloid plaque in Alzheimer's disease
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Cai, Lisheng; Liow, Jeih-San; Morse, Cheryl; Innis, Robert; Pike, Victor] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S121
EP S122
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000124
ER
PT J
AU Fazl, A
Simonyan, K
Herscovitch, P
AF Fazl, Arash
Simonyan, Kristina
Herscovitch, Peter
TI GABAergic correlates of speech production
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Simonyan, Kristina] Mt Sinai Sch Med, Dept Otolaryngol, New York, NY USA.
[Herscovitch, Peter] NIH, PET Dept, Bethesda, MD 20892 USA.
[Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S49
EP S50
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000044
ER
PT J
AU Harsha, A
Zhou, Y
Sojkova, J
Goh, J
Rahmim, A
Wong, DF
Resnick, SM
Prince, JL
AF Harsha, Amith
Zhou, Yun
Sojkova, Jitka
Goh, Joshua
Rahmim, Arman
Wong, Dean F.
Resnick, Susan M.
Prince, Jerry L.
TI Development and validation of an integrative software for automatic MRI
and [C-11]PiB dynamic PET image processing and parametric Imaging
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Harsha, Amith] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Div Neuroradiol, Baltimore, MD USA.
[Sojkova, Jitka; Goh, Joshua; Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
[Rahmim, Arman; Wong, Dean F.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Div Nucl Med, Sect High Resolut Brain PET Imaging, Baltimore, MD USA.
[Prince, Jerry L.] Johns Hopkins Univ, Dept Elect Engn, Image Anal & Commun Lab, Baltimore, MD USA.
RI Prince, Jerry/A-3281-2010
OI Prince, Jerry/0000-0002-6553-0876
NR 5
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S173
EP S174
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000182
ER
PT J
AU Hirvonen, J
Zanotti-Fregonara, P
Umhau, JC
George, DT
Rallis-Frutos, D
Lyoo, CH
Li, CT
Hines, CS
Sun, H
Terry, GE
Morse, C
Zoghbi, SS
Pike, VW
Innis, RB
Heilig, M
AF Hirvonen, Jussi
Zanotti-Fregonara, Paolo
Umhau, John C.
George, David T.
Rallis-Frutos, Denise
Lyoo, Chul Hyoung
Li, Cheng-Ta
Hines, Christina S.
Sun, Hui
Terry, Garth E.
Morse, Cheryl
Zoghbi, Sami S.
Pike, Victor W.
Innis, Robert B.
Heilig, Markus
TI Reduced cannabinoid CB1 receptor binding in alcohol dependence measured
with positron emission tomography
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Hirvonen, Jussi; Zanotti-Fregonara, Paolo; Rallis-Frutos, Denise; Lyoo, Chul Hyoung; Li, Cheng-Ta; Hines, Christina S.; Terry, Garth E.; Morse, Cheryl; Zoghbi, Sami S.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Umhau, John C.; George, David T.; Sun, Hui; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S25
EP S26
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000017
ER
PT J
AU Kreisl, T
Kreisl, W
Herscovitch, P
Innis, R
AF Kreisl, Teri
Kreisl, William
Herscovitch, Peter
Innis, Robert
TI [C-11]N-Desmethyl-Loperamide as a marker of Pgp function in patients
with gliomas
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Kreisl, Teri] NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
[Kreisl, William; Innis, Robert] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Herscovitch, Peter] Natl Inst Hlth Clin Ctr, PET Dept, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S106
EP S106
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000107
ER
PT J
AU Kreisl, W
Jenko, K
Hines, C
Lyoo, CH
Morse, C
Zoghbi, S
Kleinman, J
Pike, V
McMahon, F
Innis, R
AF Kreisl, William
Jenko, Kimberly
Hines, Christina
Lyoo, Chul Hyoung
Morse, Cheryl
Zoghbi, Sami
Kleinman, Joel
Pike, Victor
McMahon, Francis
Innis, Robert
TI Correcting for the Ala147Thr polymorphism in the gene for 18 kDa
translocator protein improves quantification of this inflammatory
biomarker with [C-11]PBR28
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Kreisl, William; Jenko, Kimberly; Hines, Christina; Lyoo, Chul Hyoung; Morse, Cheryl; Zoghbi, Sami; Pike, Victor; Innis, Robert] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kleinman, Joel] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[McMahon, Francis] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S21
EP S21
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000011
ER
PT J
AU Lohith, T
Zoghbi, S
Morse, C
Goebl, N
Tauscher, J
Pike, V
Innis, R
Fujita, M
AF Lohith, Talakad
Zoghbi, Sami
Morse, Cheryl
Goebl, Nancy
Tauscher, Johannes
Pike, Victor
Innis, Robert
Fujita, Masahiro
TI Reproducibility measurements of [C-11]NOP-1A, a new PET radioligand to
image nociceptin/orphanin FQ peptide (NOP) receptors in healthy subjects
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
ID BRAIN
C1 [Lohith, Talakad; Zoghbi, Sami; Morse, Cheryl; Pike, Victor; Innis, Robert; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Goebl, Nancy; Tauscher, Johannes] Eli Lilly & Co, Indianapolis, IN 46285 USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S134
EP S134
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000138
ER
PT J
AU Lu, SY
Zhang, Y
Kalin, JH
Gai, LS
Kosikowzki, AP
Pike, VW
AF Lu, Shuiyu
Zhang, Yi
Kalin, Jay H.
Gai, Lisheng
Kosikowzki, Alan P.
Pike, Victor W.
TI Labeling of Tubastatin A with Carbon-11 in the hydroxamic acid carbonyl
position for PET imaging of histone deacetylase 6 in brain
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
ID CHEMISTRY; INHIBITOR
C1 [Lu, Shuiyu; Zhang, Yi; Gai, Lisheng; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kalin, Jay H.; Kosikowzki, Alan P.] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA.
NR 5
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S115
EP S116
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000118
ER
PT J
AU Mohy-Ud-Din, H
Karakatsanis, NA
Price, JC
Zhou, Y
Resnick, SM
Endres, CJ
Klunk, WE
Mathis, CA
Wong, DF
Rahmim, A
AF Mohy-Ud-Din, Hassan
Karakatsanis, Nicolas A.
Price, Julie C.
Zhou, Yun
Resnick, Susan M.
Endres, Christopher J.
Klunk, William E.
Mathis, Chester A.
Wong, Dean F.
Rahmim, Arman
TI Investigation of noise-induced correlations in dual-biomarker parametric
imaging from dynamic [C-11]PiB PET
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Mohy-Ud-Din, Hassan; Karakatsanis, Nicolas A.; Zhou, Yun; Endres, Christopher J.; Wong, Dean F.; Rahmim, Arman] Johns Hopkins Univ, Baltimore, MD USA.
[Price, Julie C.; Klunk, William E.; Mathis, Chester A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S186
EP S187
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000196
ER
PT J
AU Rizzo, G
Veronese, M
Turkheimer, FE
Zanotti-Fregonara, P
Fujita, M
Zoghbi, SS
Innis, RB
Schmidt, KC
Smith, CB
Bertoldo, A
AF Rizzo, Gaia
Veronese, Mattia
Turkheimer, Federico E.
Zanotti-Fregonara, Paolo
Fujita, Masahiro
Zoghbi, Sami S.
Innis, Robert B.
Schmidt, Kathleen C.
Smith, Carolyn B.
Bertoldo, Alessandra
TI Evaluation of PET quantification sensitivity to the arterial input
function modeling
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Rizzo, Gaia; Veronese, Mattia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy.
[Turkheimer, Federico E.] Univ London Imperial Coll Sci Technol & Med, Div Expt Med, London, England.
[Zanotti-Fregonara, Paolo; Fujita, Masahiro; Zoghbi, Sami S.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Schmidt, Kathleen C.; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA.
RI Veronese, Mattia/A-6012-2013; Rizzo, Gaia/A-8697-2013
OI Veronese, Mattia/0000-0003-3562-0683; Rizzo, Gaia/0000-0001-7272-8576
NR 4
TC 1
Z9 1
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S148
EP S149
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000155
ER
PT J
AU Rizzo, G
Veronese, M
Zanotti-Fregonara, P
Fujita, M
Innis, RB
Bertoldo, A
AF Rizzo, Gala
Veronese, Mattia
Zanotti-Fregonara, Paolo
Fujita, Masahiro
Innis, Robert B.
Bertoldo, Alessandra
TI Voxel-wise quantification of [C-11](R)-rolipram PET data in human brain
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Rizzo, Gala; Veronese, Mattia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy.
[Zanotti-Fregonara, Paolo; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
RI Rizzo, Gaia/A-8697-2013; Veronese, Mattia/A-6012-2013
OI Rizzo, Gaia/0000-0001-7272-8576; Veronese, Mattia/0000-0003-3562-0683
NR 5
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S152
EP S153
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000158
ER
PT J
AU Rousset, O
Bazin, PL
Carass, A
Endres, C
Harsha, A
Pham, D
Resnick, S
Wong, DF
AF Rousset, Olivier
Bazin, Pierre-Louis
Carass, Aaron
Endres, Christopher
Harsha, Amith
Dzung Pham
Resnick, Susan
Wong, Dean F.
TI In vivo amyloid deposition in the aging brain: methodological
considerations for partial volume correction
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
ID PET
C1 [Rousset, Olivier; Wong, Dean F.] Johns Hopkins Univ, Div Nucl Med, Dept Radiol & Radiol Sci, Sect High Resolut Brain PET Imaging, Baltimore, MD USA.
[Bazin, Pierre-Louis] Max Planck Inst Human & Cognit Brain Sci, Leipzig, Germany.
[Carass, Aaron] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD USA.
[Endres, Christopher; Harsha, Amith] Johns Hopkins Univ, Div Neuroradiol, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Dzung Pham] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Resnick, Susan] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RI Rousset, Olivier/J-6053-2012
OI Rousset, Olivier/0000-0003-4414-149X
NR 7
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S187
EP S188
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000197
ER
PT J
AU Shrestha, S
Liow, JS
Gladding, R
Pike, V
Noble, P
Winslow, J
Nelson, E
Suomi, S
Pine, D
Innis, R
AF Shrestha, Saurav
Liow, Jeih-San
Gladding, Robert
Pike, Victor
Noble, Pam
Winslow, James
Nelson, Eric
Suomi, Steve
Pine, Daniel
Innis, Robert
TI PET imaging of serotonin transporter in monkeys: effects of maternal
separation, and long-term fluoxetine treatment during adolescence
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Shrestha, Saurav; Liow, Jeih-San; Gladding, Robert; Pike, Victor; Noble, Pam; Winslow, James; Nelson, Eric; Suomi, Steve; Pine, Daniel; Innis, Robert] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S32
EP S32
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000024
ER
PT J
AU Tsujikawa, T
Zoghbi, S
Hong, J
Donohue, S
Halldin, C
Pike, V
Innis, R
Fujita, M
AF Tsujikawa, Tetsuya
Zoghbi, Sami
Hong, Jinsoo
Donohue, Sean
Halldin, Christer
Pike, Victor
Innis, Robert
Fujita, Masahiro
TI Quantification of human brain cannabinoid CB1 receptors using a novel
PET radioligand, [C-11]SD5024
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Tsujikawa, Tetsuya; Zoghbi, Sami; Hong, Jinsoo; Donohue, Sean; Pike, Victor; Innis, Robert; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S133
EP S134
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000137
ER
PT J
AU Veronese, M
Schmidt, K
Smith, C
Rizzo, G
Turkheimer, F
Bertoldo, A
AF Veronese, Mattia
Schmidt, Kathleen
Smith, Carolyn
Rizzo, Gaia
Turkheimer, Federico
Bertoldo, Alessandra
TI Spectral analysis iterative filter for voxel-wise quantification of PET
tracers with irreversible uptake
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy.
[Schmidt, Kathleen; Smith, Carolyn] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA.
[Turkheimer, Federico] Univ London Imperial Coll Sci Technol & Med, Div Expt Med, London, England.
RI Rizzo, Gaia/A-8697-2013
OI Rizzo, Gaia/0000-0001-7272-8576
NR 4
TC 1
Z9 1
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S147
EP S147
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000153
ER
PT J
AU Zanotti-Fregonara, P
Hines, C
Zoghbi, S
Liow, JS
Zhang, Y
Pike, V
Drevets, W
Zarate, C
Fujita, M
Innis, R
AF Zanotti-Fregonara, Paolo
Hines, Christina
Zoghbi, Sami
Liow, Jeih-San
Zhang, Yi
Pike, Victor
Drevets, Wayne
Zarate, Carlos
Fujita, Masahiro
Innis, Robert
TI Validation of population-based and image-derived input functions in the
tracer kinetic modeling of [C-11](R)-rolipram in healthy volunteers and
depressed subjects
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Zanotti-Fregonara, Paolo; Hines, Christina; Zoghbi, Sami; Liow, Jeih-San; Zhang, Yi; Pike, Victor; Zarate, Carlos; Fujita, Masahiro; Innis, Robert] NIMH, Bethesda, MD 20892 USA.
[Drevets, Wayne] Univ Oklahoma, Sch Community Med, Tulsa, OK USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S137
EP S138
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000142
ER
PT J
AU Zhou, Y
Resnick, S
Sojkova, J
Price, J
Mathis, C
Klunk, W
Lopresti, B
Smith, G
Wong, DF
AF Zhou, Yun
Resnick, Susan
Sojkova, Jitka
Price, Julie
Mathis, Chester
Klunk, William
Lopresti, Brian
Smith, Gwenn
Wong, Dean F.
TI Evaluation of noninvasive estimation of distribution volume and
distribution volume ratio method for unbiased quantification of
multi-center [C-11]PiB human dynamic PET studies
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 9th International Symposium on Functional Neuroreceptor Mapping of the
Living Brain (NRM)
CY AUG 09-11, 2012
CL Baltimore, MD
C1 [Zhou, Yun; Smith, Gwenn; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Resnick, Susan; Sojkova, Jitka] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Price, Julie; Mathis, Chester; Klunk, William; Lopresti, Brian] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
RI Lopresti, Brian/O-2465-2016
OI Lopresti, Brian/0000-0002-0595-0203
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD AUG
PY 2012
VL 32
SU 1
BP S188
EP S189
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 983SC
UT WOS:000307138000198
ER
PT J
AU Calvo, A
Goodwin, PY
Berrian, A
Houston, AM
Meklir, S
Rajapakse, N
AF Calvo, Ahmed
Goodwin, Paula Y.
Berrian, Amber
Houston, Avril Melissa
Meklir, Samantha
Rajapakse, Nishadi
TI HRSA and NIH Guest Editors' Preface
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Editorial Material
C1 [Rajapakse, Nishadi] NIH, Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD AUG
PY 2012
VL 23
IS 3
SU S
BP 3
EP 3
PG 1
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 987JR
UT WOS:000307413700003
PM 22864482
ER
PT J
AU Haggstrom, DA
Taplin, SH
Monahan, P
Clauser, S
AF Haggstrom, David A.
Taplin, Stephen H.
Monahan, Patrick
Clauser, Steven
TI Chronic Care Model Implementation for Cancer Screening and Follow-up in
Community Health Centers
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Organizational change; organizational improvement; health services;
cancer screening
ID QUALITY IMPROVEMENT COLLABORATIVES; CHRONIC ILLNESS CARE; DISPARITIES
COLLABORATIVES; TEAM EFFECTIVENESS; DIABETES CARE; UNITED-STATES;
SERVICES; PHYSICIANS; PROGRAM; IMPACT
AB Background. The Health Disparities Cancer Collaborative (HDCC) implemented six components of the Chronic Care Model (CCM) to increase cancer screening and follow-up among underserved populations from 2003-05. Methods. Organizational surveys were administered among 19 community health centers participating in the HDCC and 22 matched control centers. Health care providers, directors, financial officers, information systems personnel, and general staff completed surveys to measure CCM implementation (primary outcome) and cancer care process improvement (secondary outcome) at the organizational level. Results. The HDCC community health centers were more likely to report CCM implementation than control centers. The HDCC and control centers were equally likely to report cancer care process improvement, but CCM implementation was significantly associated with process improvement in adjusted models. Conclusions. Implementation of CCM, not solely HDCC participation, was associated with cancer care process improvement. Organizational and individual change is challenging among the large, healthy populations eligible for cancer screening.
C1 [Haggstrom, David A.; Monahan, Patrick] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Taplin, Stephen H.] NCI, Proc Care Res Branch, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA.
[Clauser, Steven] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
RP Haggstrom, DA (reprint author), Richard L Roudebush VA Med Ctr, 1481 W 10th St 11H, Indianapolis, IN 46202 USA.
EM dahaggst@iupui.edu
NR 37
TC 5
Z9 5
U1 1
U2 13
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD AUG
PY 2012
VL 23
IS 3
SU S
BP 49
EP 66
PG 18
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 987JR
UT WOS:000307413700008
PM 22864487
ER
PT J
AU Fernandes, R
Braun, KL
Spinner, JR
Sturdevant, C
Ancheta, SJ
Yoshimura, SR
Compton, M
Wang, JH
Lee, CJ
AF Fernandes, Ritabelle
Braun, Kathryn L.
Spinner, Jovonni R.
Sturdevant, Cynthia
Ancheta, Sharonne J.
Yoshimura, Sheryl R.
Compton, Merlita
Wang, Jo-Hsi
Lee, Carolyn J.
TI Healthy Heart, Healthy Family: A NHLBI/HRSA Collaborative Employing
Community Health Workers to Improve Heart Health
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Asian Americans; cardiovascular disease; cardiovascular risk factors;
community health workers; cultural competency; Filipino Americans;
health education
ID RISK
AB Kokua Kalihi Valley, a federally qualified health center in Hawaii, collaborated with the National Heart, Lung, and Blood Institute to test the efficacy of community health workers (CHWs) to deliver the Healthy Heart, Healthy Family curriculum to low-income Filipinos with cardiovascular disease (CVD) risk factors. At 12 months, significant improvements were seen in health behaviors, knowledge, and self-efficacy in managing chronic diseases. We also observed decreases in total cholesterol from 186.25 mg/dl to 170.88 mg/dl (p=.001), low-density lipoprotein from 114.43 mg/dl to 103.04 mg/dl (p=.013), and fasting blood glucose from 117.95 mg/dl to 109.07 mg/dl (p=.034). Although these changes were statistically significant, they are small and not clinically meaningful in reducing CVD risk. The high-density lipoprotein was 3.3 mg/dl lower (worse) at 12 months (p=.003), mean values for blood pressure, BMI, and waist circumference increased. Community health workers can be trained to deliver evidence-based curricula that improve health behaviors and increase self-efficacy in managing chronic diseases.
C1 [Fernandes, Ritabelle; Sturdevant, Cynthia; Ancheta, Sharonne J.; Yoshimura, Sheryl R.; Compton, Merlita; Wang, Jo-Hsi; Lee, Carolyn J.] Kokua Kalihi Valley Comprehens Family Serv, Honolulu, HI USA.
[Braun, Kathryn L.] Univ Hawaii, John A Burns Sch Med, Off Publ Hlth Studies, Honolulu, HI 96822 USA.
[Spinner, Jovonni R.] NHLBI, Div Applicat Res Discoveries, NIH, Bethesda, MD 20892 USA.
RP Fernandes, R (reprint author), 2239 N Sch St, Honolulu, HI 96819 USA.
EM rfernandes@kkv.net
FU NIMHD NIH HHS [U54 MD007584]; PHS HHS [H80CS00776-06-03]
NR 18
TC 1
Z9 1
U1 2
U2 6
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD AUG
PY 2012
VL 23
IS 3
BP 988
EP 999
PG 12
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 987OB
UT WOS:000307425800010
PM 24212152
ER
PT J
AU Lopez-Class, M
Luta, G
Noone, AM
Canar, J
Selksy, C
Huerta, E
Mandelblatt, J
AF Lopez-Class, Maria
Luta, Gheorghe
Noone, Anne-Michelle
Canar, Janet
Selksy, Claire
Huerta, Elmer
Mandelblatt, Jeanne
TI Patient and Provider Factors Associated with Colorectal Cancer Screening
in Safety Net Clinics Serving Low-income, Urban Immigrant Latinos
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Latinos; colorectal cancer; screening; immigrants; obesity
ID UNITED-STATES; BARRIERS; OBESITY; COLON; CARE; FACILITATORS; AMERICANS;
WHITE; WOMEN; RISK
AB Background. Latinos have lower colorectal cancer screening rates than Whites. Methods. We reviewed a random sample of charts between July 2009 and February 2010 of safety-net clinic of 840 immigrants (50 years and older) from Central and South America receiving care. Logistic regression evaluated associations of ever vs. never screening, patient and physician factors. Results. Ever screening rates were 24.5%, and only 17% of charts noted a physician screening recommendation. However, the odds of screening were 9.89 times higher (95% CI: 6.25-15.64, p<.001) among patients with a physician recommendation vs. those without, considering covariates. The odds of screening were 0.61 times lower (95% CI: 0.40-0.92, p=.02) in patients with a body mass index >= 30 vs. <30. Conclusions. While rates were low, determinants of screening were similar in this Latino subgroup to those reported in other Latino and non-Latino populations. Low rates of documented physician screening recommendations may indicate a potential missed opportunity for cancer control in safety-net clinics.
C1 [Lopez-Class, Maria] NICHD, NIH, Bethesda, MD 20814 USA.
[Huerta, Elmer; Mandelblatt, Jeanne] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Canar, Janet; Selksy, Claire] Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20057 USA.
[Noone, Anne-Michelle] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA.
RP Lopez-Class, M (reprint author), NICHD, NIH, Bethesda, MD 20814 USA.
EM lopezclassm@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]; NCI NIH HHS [P30CA51008, U01
CA114593, U01 CA86114, U01 CA086114, K05 CA096940, K05 CA96940, P30
CA051008]
NR 36
TC 3
Z9 3
U1 1
U2 6
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD AUG
PY 2012
VL 23
IS 3
BP 1011
EP 1019
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 987OB
UT WOS:000307425800012
PM 24212154
ER
PT J
AU Kurdziel, KA
Shih, JH
Apolo, AB
Lindenberg, L
Mena, E
McKinney, YY
Adler, SS
Turkbey, B
Dahut, W
Gulley, JL
Madan, RA
Landgren, O
Choyke, PL
AF Kurdziel, Karen A.
Shih, Joanna H.
Apolo, Andrea B.
Lindenberg, Liza
Mena, Esther
McKinney, Yolanda Y.
Adler, Stephen S.
Turkbey, Baris
Dahut, William
Gulley, James L.
Madan, Ravi A.
Landgren, Ola
Choyke, Peter L.
TI The Kinetics and Reproducibility of F-18-Sodium Fluoride for Oncology
Using Current PET Camera Technology
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE bone scanning; oncology; PET/CT; prostate cancer; multiple myeloma
ID F-18 FLUORIDE; LUNG-CANCER; F-18-FLUORIDE PET/CT; BONE METASTASES;
SPECT; PROSTATE; BREAST; SCANS; ION
AB We evaluated the kinetics of F-18-sodium fluoride (NaF) and reassessed the recommended dose, optimal uptake period, and reproducibility using a current-generation PET/CT scanner. Methods: In this prospective study, 73 patients (31 patients with multiple myeloma or myeloma precursor disease and 42 with prostate cancer) were injected with a mean administered dose of 141 MBq of F-18-NaF. Sixty patients underwent 3 sequential sessions of 3-dimensional PET/CT of the torso beginning approximately 15 min after F-18-NaF injection, followed by whole-body 3-dimensional PET/CT at 2 h. The remaining 13 prostate cancer patients were imaged only at 2 and 3 h after injection. Twenty-one prostate cancer patients underwent repeated baseline studies (mean interval, 5.9 d) to evaluate reproducibility. Results: The measured effective dose was 0.017 mSv/MBq, with the urinary bladder, osteogenic cells, and red marrow receiving the highest doses at 0.080, 0.077, and 0.028 mGy/MBq, respectively. Visual analysis showed that uptake in both normal and abnormal bone increased with time; however, the rate of increase decreased with time. A semiautomated workflow provided objective uptake parameters, including the mean standardized uptake value of all pixels within bone with SUVs greater than 10 and the average of the mean SUV of all malignant lesions identified by the algorithm. The values of these parameters for the images beginning at approximately 15 min and approximately 35 min were significantly different (0.3% change per minute). Differences between the later imaging time points were not significant (P < 0.01). Repeated baseline studies showed high intraclass correlations (>0.9) and relatively low critical percentage change (the value above which a change can be considered real) for these parameters. The tumor-to-normal bone ratio, based on the maximum SUV of identified malignant lesions, decreased with time; however, this difference was small, estimated at approximately 0.16%/min in the first hour. Conclusion: F-18-NaF PET/CT images obtained with modest radiation exposures can result in highly reproducible imaging parameters. Although the tumor-to-normal bone ratio decreases slightly with time, the high temporal dependence during uptake periods less than 30 min may limit accurate quantitation. An uptake period of 60 +/- 30 min has limited temporal dependence while maintaining a high tumor-to-normal bone ratio.
C1 [Kurdziel, Karen A.; Lindenberg, Liza; Mena, Esther; McKinney, Yolanda Y.; Adler, Stephen S.; Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Apolo, Andrea B.; Dahut, William; Gulley, James L.; Madan, Ravi A.; Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kurdziel, KA (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, 10 Ctr Dr,Room B3B403, Bethesda, MD 20892 USA.
EM karen.kurdziel@nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Center for Cancer Research/National Cancer Institute/National Institutes
of Health
FX We thank our imaging technologists Gideon Kwarteng and Phil Eclarinal,
without whom no data would have been obtained. We also thank the
reviewers of this manuscript, whose advice and recommendations improved
the quality of this article. This work was funded by the Center for
Cancer Research/National Cancer Institute/National Institutes of Health.
No other potential conflict of interest relevant to this article was
reported.
NR 23
TC 20
Z9 21
U1 1
U2 3
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD AUG
PY 2012
VL 53
IS 8
BP 1175
EP 1184
DI 10.2967/jnumed.111.100883
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 984OT
UT WOS:000307201300017
PM 22728263
ER
PT J
AU Shahzad-ul-Hussan, S
Ghirlando, R
Dogo-Isonagie, CI
Igarashi, Y
Balzarini, J
Bewley, CA
AF Shahzad-ul-Hussan, Syed
Ghirlando, Rodolfo
Dogo-Isonagie, Cajetan I.
Igarashi, Yasuhiro
Balzarini, Jan
Bewley, Carole A.
TI Characterization and Carbohydrate Specificity of Pradimicin S
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MANNOSE-BINDING; ANTIBIOTICS; BMY-28864;
ANALOG; SITE
AB The pradimicin family of antibiotics is attracting attention due to its anti-infective properties and as a model for understanding the requirements for carbohydrate recognition by small molecules. Members of the pradimicin family are unique among natural products in their ability to bind sugars in a Ca2+-dependent manner, but the oligomerization to insoluble aggregates that occurs upon Ca2+ binding has prevented detailed characterization of their carbohydrate specificity and biologically relevant form. Here we take advantage of the water solubility of pradimicin S (PRM-S), a sulfated glucose-containing analogue of pradimicin A (PRM-A), to show by NMR spectroscopy and analytical ultracentrifugation that at biologically relevant concentrations, PRM-S binds Ca2+ to form a tetrameric species that selectively binds and engulfs the trisaccharide Man alpha 1-3(Man alpha 1-6)Man over mannose or mannobiose. In functional HIV-1 entry assays, IC50 values of 2-4 mu M for PRM-S corrrelate with the concentrations at which oligomerization occurs as well as the affinities with which PRM-S binds the HIV surface envelope glycoprotein gp120. Together these data reveal the biologically active form of PRM-S, provide an explanation for previous speculations that PRM-A may contain a second mannose binding site, and expand our understanding of the characteristics that can engender a small molecule with the ability to function as a carbohydrate receptor.
C1 [Shahzad-ul-Hussan, Syed; Dogo-Isonagie, Cajetan I.; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Igarashi, Yasuhiro] Toyama Prefectural Univ, Biotechnol Res Ctr, Imizu, Toyama 9390398, Japan.
[Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium.
[Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
FU National Institutes of Health (NIDDK); KU Leuven [PF-10/18]; Office of
the Director, NIH
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health (NIDDK), and KU Leuven, PF-10/18
(J.B.). C.D.-I. is a recipient of an Intramural AIDS Research Fellow
award, Office of the Director, NIH.
NR 18
TC 8
Z9 8
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 1
PY 2012
VL 134
IS 30
BP 12346
EP 12349
DI 10.1021/ja303860m
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 981CH
UT WOS:000306942600007
PM 22788706
ER
PT J
AU Sugaya, L
Hasin, DS
Olfson, M
Lin, KH
Grant, BF
Blanco, C
AF Sugaya, Luisa
Hasin, Deborah S.
Olfson, Mark
Lin, Keng-Han
Grant, Bridget F.
Blanco, Carlos
TI Child physical abuse and adult mental health: A national study
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; PEDIATRIC
PRIMARY-CARE; ALCOHOL-USE-DISORDER; IV AUDADIS-IV; HOUSEHOLD
DYSFUNCTION; CORPORAL PUNISHMENT; BEHAVIOR PROBLEMS; TRANSPORTER GENE;
MULTIPLE FORMS
AB This study characterizes adults who report being physically abused during childhood, and examines associations of reported type and frequency of abuse with adult mental health. Data were derived from the 20002001 and 20042005 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the U.S. population. Weighted means, frequencies, and odds ratios of sociodemographic correlates and prevalence of psychiatric disorders were computed. Logistic regression models were used to examine the strength of associations between child physical abuse and adult psychiatric disorders adjusted for sociodemographic characteristics, other childhood adversities, and comorbid psychiatric disorders. Child physical abuse was reported by 8% of the sample and was frequently accompanied by other childhood adversities. Child physical abuse was associated with significantly increased adjusted odds ratios (AORs) of a broad range of DSM-IV psychiatric disorders (AOR = 1.162.28), especially attention-deficit hyperactivity disorder, posttraumatic stress disorder, and bipolar disorder. A dose-response relationship was observed between frequency of abuse and several adult psychiatric disorder groups; higher frequencies of assault were significantly associated with increasing adjusted odds. The long-lasting deleterious effects of child physical abuse underscore the urgency of developing public health policies aimed at early recognition and prevention.
C1 [Sugaya, Luisa; Hasin, Deborah S.; Olfson, Mark; Lin, Keng-Han; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hasin, Deborah S.; Olfson, Mark; Blanco, Carlos] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA.
RP Blanco, C (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA.
EM cb255@columbia.edu
RI Blanco, Carlos/I-4906-2013
OI Blanco, Carlos/0000-0001-6187-3057
FU Intramural NIH HHS; NIAAA NIH HHS [K02 AA000161, K05AA00161, U01
AA018111, U01AA018111]; NIDA NIH HHS [DA019606, DA020783, DA023200, K02
DA023200, R01 DA019606, R01 DA020783]; NIMH NIH HHS [MH082773, MH076051,
R01 MH076051, R01 MH082773]; NIMHD NIH HHS [P60 MD000206]
NR 47
TC 62
Z9 62
U1 3
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2012
VL 25
IS 4
BP 384
EP 392
DI 10.1002/jts.21719
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 983HI
UT WOS:000307110000004
PM 22806701
ER
PT J
AU Ballyns, JJ
Turo, D
Otto, P
Shah, JP
Hammond, J
Gebreab, T
Gerber, LH
Sikdar, S
AF Ballyns, Jeffrey J.
Turo, Diego
Otto, Paul
Shah, Jay P.
Hammond, Jennifer
Gebreab, Tadesse
Gerber, Lynn H.
Sikdar, Siddhartha
TI Office-Based Elastographic Technique for Quantifying Mechanical
Properties of Skeletal Muscle
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE biomechanics; myofascial trigger points; shear wave elastography;
ultrasound
ID MYOFASCIAL TRIGGER POINTS; MAGNETIC-RESONANCE ELASTOGRAPHY; IN-VIVO;
SOFT-TISSUE; BIOLOGICAL TISSUES; TAUT BANDS; PAIN; ELASTICITY;
QUANTIFICATION; SONOELASTOGRAPHY
AB Objectives-Our objectives were to develop a new, efficient, and easy-to-administer approach to ultrasound elastography and assess its ability to provide quantitative characterization of viscoelastic properties of skeletal muscle in an outpatient clinical environment. We sought to show its validity and clinical utility in assessing myofascial trigger points, which are associated with myofascial pain syndrome.
Methods-Ultrasound imaging was performed while the muscle was externally vibrated at frequencies in the range of 60 to 200 Hz using a handheld vibrator. The spatial gradient of the vibration phase yielded the shear wave speed, which is related to the viscoelastic properties of tissue. The method was validated using a calibrated experimental phantom, the biceps brachii muscle in healthy volunteers (n = 6), and the upper trapezius muscle in symptomatic patients with axial neck pain (n = 13) and asymptomatic (pain-free) control participants (11 = 9).
Results-Using the experimental phantom, our method was able to quantitatively measure the shear moduli with error rates of less than 20%. The mean shear modulus +/- SD in the normal biceps brachii measured 12.5 +/- 3.4 kPa, within the range of published values using more sophisticated methods. Shear wave speeds in active myofascial trigger points and the surrounding muscle tissue were significantly higher than those in normal tissue at high frequency excitations (>100 Hz; P < .05).
Conclusions-Off-the-shelf office-based equipment can be used to quantitatively characterize skeletal muscle viscoelastic properties with estimates comparable to those using more sophisticated methods. Our preliminary results using this method indicate that patients with spontaneous neck pain and symptomatic myofascial trigger points have increased tissue heterogeneity at the trigger point site and the surrounding muscle tissue.
C1 [Ballyns, Jeffrey J.; Otto, Paul; Sikdar, Siddhartha] George Mason Univ, Dept Elect & Comp Engn, Fairfax, VA 22030 USA.
[Turo, Diego; Sikdar, Siddhartha] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA.
[Gerber, Lynn H.] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA.
[Shah, Jay P.; Hammond, Jennifer; Gebreab, Tadesse] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Sikdar, S (reprint author), George Mason Univ, Dept Elect & Comp Engn, 4400 Univ Dr,MS 1G5, Fairfax, VA 22030 USA.
EM ssikdar@gmu.edu
FU National Institutes of Health (NIH); Clinical Center and Office of the
Director, NIH from National Institute of Arthritis and Musculoskeletal
and Skin Diseases, NIH [1R01-AR057348]; National Science Foundation
[0953652]
FX We thank Juliana Heimur for editing this manuscript. This research was
supported in part by the Intramural Research Program, National
Institutes of Health (NIH), the Clinical Center and Office of the
Director, NIH, grant 1R01-AR057348 from the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, NIH, and grant 0953652
from the National Science Foundation.
NR 37
TC 12
Z9 12
U1 0
U2 6
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
EI 1550-9613
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD AUG
PY 2012
VL 31
IS 8
BP 1209
EP 1219
PG 11
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 981QS
UT WOS:000306985100009
PM 22837285
ER
PT J
AU Schwartz, GJ
Schneider, MF
Maier, PS
Moxey-Mims, M
Dharnidharka, VR
Warady, BA
Furth, SL
Munoz, A
AF Schwartz, George J.
Schneider, Michael F.
Maier, Paula S.
Moxey-Mims, Marva
Dharnidharka, Vikas R.
Warady, Bradley A.
Furth, Susan L.
Munoz, Alvaro
TI Improved equations estimating GFR in children with chronic kidney
disease using an immunonephelometric determination of cystatin C
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE children; chronic kidney disease; clinical nephrology; glomerular
filtration rate; pediatric nephrology
ID GLOMERULAR-FILTRATION-RATE; PLASMA IOHEXOL DISAPPEARANCE; SERUM
CYSTATIN; NONINVASIVE ESTIMATION; PREDICTION EQUATIONS;
GENERAL-POPULATION; INULIN-CLEARANCE; CREATININE; MARKER; INFANTS
AB The Chronic Kidney Disease in Children study is a cohort of about 600 children with chronic kidney disease (CKD) in the United States and Canada. The independent variable for our observations was a measurement of glomerular filtration rate (GFR) by iohexol disappearance (iGFR) at the first two visits 1 year apart and during alternate years thereafter. In a previous report, we had developed GFR estimating equations utilizing serum creatinine, blood urea nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric method; however, the correlation coefficient of cystatin C and GFR (-0.69) was less robust than expected. Therefore, 495 samples were re-assayed using immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well correlated with iGFR as was height/serum creatinine (both 0.88). We developed a new GFR estimating equation using a random 2/3 of 965 person-visits and applied it to the remaining 1/3 as a validation data set. In the validation data set, the correlation of the estimated GFR with iGFR was 0.92 with high precision and no bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively. This equation works well in children with CKD in a range of GFR from 15 to 75 ml/min per 1.73m(2). Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR.
Kidney International ( 2012) 82, 445- 453; doi:10.1038/ki.2012.169; published online 23 May 2012
C1 [Schwartz, George J.] Univ Rochester, Med Ctr, Sch Med, Rochester, NY 14642 USA.
[Schneider, Michael F.; Munoz, Alvaro] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD USA.
[Dharnidharka, Vikas R.] Univ Florida, Coll Med, Gainesville, FL USA.
[Dharnidharka, Vikas R.] Shands Childrens Hosp, Gainesville, FL USA.
[Warady, Bradley A.] Childrens Mercy Hosp, Kansas City, MO 64108 USA.
[Furth, Susan L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Schwartz, GJ (reprint author), Univ Rochester, Med Ctr, Sch Med, Box 777,601 Elmwood Ave, Rochester, NY 14642 USA.
EM george_schwartz@urmc.rochester.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Neurological Disorders and Stroke; National
Institute of Child Health and Human Development; National Heart, Lung,
and Blood Institute [U01 DK82194, U01-DK-66143, U01-DK-66174,
U01-DK-66116]
FX Data in this manuscript were collected by the Chronic Kidney Disease in
Children prospective cohort study (CKiD) with clinical coordinating
centers (Principal Investigators) at Children's Mercy Hospital and the
University of Missouri - Kansas City (BAW) and The Children's Hospital
of Philadelphia (SLF), data coordinating center at the Johns Hopkins
Bloomberg School of Public Health (AM), and the Central Biochemistry
Laboratory at the University of Rochester (GJS). The CKiD study is
funded by the National Institute of Diabetes and Digestive and Kidney
Diseases, with additional funding from the National Institute of
Neurological Disorders and Stroke, the National Institute of Child
Health and Human Development, and the National Heart, Lung, and Blood
Institute (U01 DK82194, U01-DK-66143, U01-DK-66174, and U01-DK-66116).
The CKiD website is located at http://www.statepi.jhsph.edu/ckid. We are
grateful to Nicholas Miravalle for his care and attention given to the
immunonephelometric cystatin C assay and to Tai Kwong and Brian Erway
for their excellent performance and maintenance of the iohexol assay. We
are also grateful to Mary Lou Gantzer of Siemens for her support in
developing the immunonephelometric cystatin C assay at the Central
Biochemistry Laboratory, and to GE Healthcare (Rich Vitti) for providing
the Omnipaque 300 for the iohexol GFR studies.
NR 49
TC 89
Z9 92
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD AUG
PY 2012
VL 82
IS 4
BP 445
EP 453
DI 10.1038/ki.2012.169
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 982XF
UT WOS:000307078000012
PM 22622496
ER
PT J
AU Herz, J
Zinselmeyer, BH
McGavern, DB
AF Herz, Jasmin
Zinselmeyer, Bernd H.
McGavern, Dorian B.
TI Two-Photon Imaging of Microbial Immunity in Living Tissues
SO MICROSCOPY AND MICROANALYSIS
LA English
DT Article; Proceedings Paper
CT 7th Omaha Imaging Symposium
CY APR 08, 2011
CL Creighton Univ, Omaha, NE
HO Creighton Univ
DE two-photon microscopy; virus; immunity; infection
ID CD8(+) T-CELLS; SUBCAPSULAR SINUS MACROPHAGES; HOST-PATHOGEN
INTERACTIONS; GREEN-FLUORESCENT PROTEIN; BEARING DENDRITIC CELLS;
CENTRAL-NERVOUS-SYSTEM; IN-VIVO; LYMPH-NODES; MYCOBACTERIAL GRANULOMAS;
2ND-HARMONIC GENERATION
AB The immune system is highly evolved and can respond to infection throughout the body. Pathogen-specific immune cells are usually generated in secondary lymphoid tissues (e.g., spleen, lymph nodes) and then migrate to sites of infection where their functionality is shaped by the local milieu. Because immune cells are so heavily influenced by the infected tissue in which they reside, it is important that their interactions and dynamics be studied in vivo. Two-photon microscopy is a powerful approach to study host-immune interactions in living tissues, and recent technical advances in the field have enabled researchers to capture movies of immune cells and infectious agents operating in real time. These studies have shed light on pathogen entry and spread through intact tissues as well as the mechanisms by which innate and adaptive immune cells participate in thwarting infections. This review focuses on how two-photon microscopy can be used to study tissue-specific immune responses in vivo, and how this approach has advanced our understanding of host-immune interactions following infection.
C1 [Herz, Jasmin; Zinselmeyer, Bernd H.; McGavern, Dorian B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP McGavern, DB (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
FU Intramural NIH HHS [ZIA NS003112-04, ZIA NS003111-04]
NR 77
TC 9
Z9 9
U1 0
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1431-9276
J9 MICROSC MICROANAL
JI Microsc. microanal.
PD AUG
PY 2012
VL 18
IS 4
BP 730
EP 741
DI 10.1017/S1431927612000281
PG 12
WC Materials Science, Multidisciplinary; Microscopy
SC Materials Science; Microscopy
GA 984EF
UT WOS:000307171900013
PM 22846498
ER
PT J
AU Hong, H
Zhang, Y
Severin, GW
Yang, YN
Engle, JW
Niu, G
Nickles, RJ
Chen, XY
Leigh, BR
Barnhart, TE
Cai, WB
AF Hong, Hao
Zhang, Yin
Severin, Gregory W.
Yang, Yunan
Engle, Jonathan W.
Niu, Gang
Nickles, Robert J.
Chen, Xiaoyuan
Leigh, Bryan R.
Barnhart, Todd E.
Cai, Weibo
TI Multimodality Imaging of Breast Cancer Experimental Lung Metastasis with
Bioluminescence and a Monoclonal Antibody Dual-Labeled with Zr-89 and
IRDye 800CW
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE breast cancer; lung metastasis; positron emission tomography (PET);
near-infrared fluorescence (NIRF); tumor angiogenesis; CD105 (endoglin);
Zr-89
ID POSITRON-EMISSION-TOMOGRAPHY; P-ISOTHIOCYANATOBENZYL-DESFERRIOXAMINE;
IN-VIVO; TUMOR VASCULATURE; SOLID TUMORS; BIFUNCTIONAL CHELATE; ENDOGLIN
CD105; IMMUNO-PET; THERAPY; EXPRESSION
AB Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and Zr-89 to yield Zr-89-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of Zr-89-Df-TRC105-800CW was 8.7 +/- 1.4, 10.9 +/- 0.5, and 9.7 +/- 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with Zr-89-Df-cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD 105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal.
C1 [Hong, Hao; Yang, Yunan; Cai, Weibo] Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA.
[Zhang, Yin; Severin, Gregory W.; Engle, Jonathan W.; Nickles, Robert J.; Cai, Weibo] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA.
[Niu, Gang; Chen, Xiaoyuan; Barnhart, Todd E.] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Leigh, Bryan R.] TRACON Pharmaceut Inc, San Diego, CA 92122 USA.
[Cai, Weibo] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA.
RP Cai, WB (reprint author), Univ Wisconsin, Dept Radiol, Room 7137,1111 Highland Ave, Madison, WI 53705 USA.
EM wcai@uwhealth.org
RI Hong, Hao/K-6035-2012; Cai, Weibo/B-9174-2008; Yang, Yunan/I-3451-2014;
Severin, Gregory/C-2230-2015; Zhang, Yin/E-6547-2015;
OI Cai, Weibo/0000-0003-4641-0833; Severin, Gregory/0000-0003-1189-7311;
Engle, Jonathan W/0000-0002-3399-7228; Barnhart,
Todd/0000-0002-9981-2150
FU University of Wisconsin Carbone Cancer Center; Department of Defense
[W81XWH-11-1-0644, W81XWH-11-1-0648]; NCRR [1UL1RR025011]; NIH [5 T32
CA009206-32]
FX This work is supported, in part, by the University of Wisconsin Carbone
Cancer Center, the Department of Defense (W81XWH-11-1-0644 and
W81XWH-11-1-0648), NCRR 1UL1RR025011, and the NIH through the UW
Radiological Sciences Training Program 5 T32 CA009206-32. We thank Dr.
Jamey P. Weichert and Mohammed Farhoud for their help with the imaging
studies.
NR 53
TC 37
Z9 37
U1 2
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD AUG
PY 2012
VL 9
IS 8
BP 2339
EP 2349
DI 10.1021/mp300277f
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 983ZU
UT WOS:000307158000022
PM 22784250
ER
PT J
AU Park, H
Bourla, AB
Kastner, DL
Colbert, RA
Siegel, RM
AF Park, Heiyoung
Bourla, Ariel Bulua
Kastner, Daniel L.
Colbert, Robert A.
Siegel, Richard M.
TI Lighting the fires within: the cell biology of autoinflammatory diseases
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID FAMILIAL MEDITERRANEAN FEVER; UNFOLDED PROTEIN RESPONSE;
ENDOPLASMIC-RETICULUM STRESS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; CHRONIC
GRANULOMATOUS-DISEASE; JUVENILE IDIOPATHIC ARTHRITIS; NALP3
INFLAMMASOME; NLRP3 INFLAMMASOME; PERIODIC SYNDROME; TNF RECEPTOR
AB Autoinflammatory diseases are characterized by seemingly unprovoked pathological activation of the innate immune system in the absence of autoantibodies or autoreactive T cells. Discovery of the causative mutations underlying several monogenic autoinflammatory diseases has identified key regulators of innate immune responses. Recent studies have highlighted the role of misfolding, oligomerization and abnormal trafficking of pathogenic mutant proteins in triggering autoinflammation, and suggest that more common rheumatic diseases may have an autoinflammatory component. This coincides with recent discoveries of new links between endoplasmic reticulum stress and inflammatory signalling pathways, which support the emerging view that autoinflammatory diseases may be due to pathological dysregulation of stress-sensing pathways that normally function in host defence.
C1 [Park, Heiyoung; Bourla, Ariel Bulua; Siegel, Richard M.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA.
[Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Colbert, Robert A.] NIAMS, Pediat Translat Res Branch, NIH, Bethesda, MD USA.
RP Siegel, RM (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA.
EM rsiegel@nih.gov
FU Intramural Research Program of the US National Institutes of Health
FX We would like to thank M. Pelletier, I. Aksentijevich and R.
Goldbach-Mansky for critical reading and helpful comments on the
manuscript. This work was supported by the Intramural Research Program
of the US National Institutes of Health.
NR 104
TC 59
Z9 59
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD AUG
PY 2012
VL 12
IS 8
BP 570
EP 580
DI 10.1038/nri3261
PG 11
WC Immunology
SC Immunology
GA 978RI
UT WOS:000306762500011
PM 22828911
ER
PT J
AU Hoy, WE
Hughson, MD
Winkler, CA
Douglas-Denton, RN
Mott, SA
Bertram, JF
Kopp, JB
AF Hoy, W. E.
Hughson, M. D.
Winkler, C. A.
Douglas-Denton, R. N.
Mott, S. A.
Bertram, J. F.
Kopp, J. B.
TI THE APOL1 GENOTYPE IN AFRICAN AMERICANS IS ASSOCIATED WITH GLOMERULAR,
RENAL AND CARDIAC HYPERTROPHY, AS WELL AS HYPERTENSION AND
CARDIOVASCULAR DISEASE
SO NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Hoy, W. E.; Mott, S. A.] Univ Queensland, Sch Med, Ctr Chron Dis, Brisbane, Qld, Australia.
[Hughson, M. D.] Univ Mississippi, Med Ctr, Jackson, MS USA.
[Winkler, C. A.] NCI, Bethesda, MD 20892 USA.
[Kopp, J. B.] NIDDK, NIH, Bethesda, MD USA.
[Douglas-Denton, R. N.; Bertram, J. F.] Monash Univ, Dept Anat & Dev Biol, Melbourne, Vic 3004, Australia.
RI Hoy, Wendy/A-7325-2010; Bertram, John/I-2588-2014; mott,
susan/F-6262-2010
OI Hoy, Wendy/0000-0002-8405-1539; Bertram, John/0000-0001-5863-6464; mott,
susan/0000-0003-0117-4718
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1320-5358
J9 NEPHROLOGY
JI Nephrology
PD AUG
PY 2012
VL 17
SU 2
SI SI
MA 073
BP 46
EP 46
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 989EZ
UT WOS:000307544400074
ER
PT J
AU Soulakova, JN
Hartman, AM
Liu, BM
Willis, GB
Augustine, S
AF Soulakova, Julia N.
Hartman, Anne M.
Liu, Benmei
Willis, Gordon B.
Augustine, Steve
TI Reliability of Adult Self-Reported Smoking History: Data from the
Tobacco Use Supplement to the Current Population Survey 2002-2003 Cohort
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; AGE-OF-ONSET; SOCIAL
DESIRABILITY; CIGARETTE-SMOKING; VALIDITY; SMOKERS; BIAS
AB Introduction: This study examined the reliability of self-reported smoking history measures. The key measures of interest were time since completely quitting smoking among former smokers; age at which fairly regular smoking was initiated among former and current smokers; the number of cigarettes smoked per day and the number of years of daily smoking among former smokers; and never smoking. Another goal was to examine sociodemographic factors and interview method as potential predictors of the odds of strict agreement in responses.
Methods: Data from the 2002-2003 Tobacco Use Supplement to the Current Population Survey were examined. Descriptive analysis was performed to detect discrepant data patterns, and intraclass and Pearson correlations and kappa coefficients were used to assess reporting consistency over the 12-month interval. Multiple logistic regression models with replicate weights were built and fitted to identify factors influencing the logit of agreement for each measure of interest.
Results: All measures revealed at least moderate levels of overall agreement. However, upon closer examination, a few measures also showed some considerable differences in absolute value. The highest percentage of these differences was observed for former smokers' reports of the number of years smoking every day.
Conclusions: Overall, the data suggest that self-reported smoking history characteristics are reliable. The logit of agreement over a 12-month period is shown to depend on a few sociodemographic characteristics as well as their interactions with each other and with interview method.
C1 [Soulakova, Julia N.; Augustine, Steve] Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA.
[Hartman, Anne M.] NCI, Risk Factors Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Liu, Benmei] NCI, Stat Methodol & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Willis, Gordon B.] NCI, Off Associate Director, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Soulakova, JN (reprint author), Univ Nebraska, Dept Stat, 340 Hardin Hall N, Lincoln, NE 68583 USA.
EM jsoulakova2@unl.edu
RI Reis, Aline/G-9573-2012
FU NCI at the National Institutes of Health [HHSN261200900395P]
FX This work was supported by the NCI at the National Institutes of Health
(sponsor award number HHSN261200900395P) awarded to JNS.
NR 30
TC 11
Z9 11
U1 0
U2 2
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 AUG
PY 2012
VL 14
IS 8
BP 952
EP 960
DI 10.1093/ntr/ntr313
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 987PX
UT WOS:000307430700009
PM 22318688
ER
PT J
AU Kosa, P
Szabo, R
Molinolo, AA
Bugge, TH
AF Kosa, P.
Szabo, R.
Molinolo, A. A.
Bugge, T. H.
TI Suppression of Tumorigenicity-14, encoding matriptase, is a critical
suppressor of colitis and colitis-associated colon carcinogenesis
SO ONCOGENE
LA English
DT Article
DE inflammatory bowel disease; intestinal barrier; colon carcinogenesis
ID INFLAMMATORY-BOWEL-DISEASE; SERINE-PROTEASE MATRIPTASE; HEPATOCYTE
GROWTH-FACTOR; COLORECTAL-CANCER; ULCERATIVE-COLITIS; MOUSE MODEL;
MATRIX METALLOPROTEINASES; PLASMINOGEN ACTIVATION; INTESTINAL
HOMEOSTASIS; BARRIER FUNCTION
AB Colitis-associated colorectal cancers are an etiologically distinct subgroup of colon cancers that occur in individuals suffering from inflammatory bowel disease and arise as a consequence of persistent exposure of hyperproliferative epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in the intestinal epithelial barrier has been proposed to be one of several factors that contribute to the inappropriate immune response to the commensal microbiota that underlies inflammatory bowel disease. Matriptase is a membrane-anchored serine protease encoded by Suppression of Tumorigenicity-14 (ST14) that strengthens the intestinal epithelial barrier by promoting tight junction formation. Here, we show that intestinal epithelial-specific ablation of St14 in mice causes formation of colon adenocarcinoma with very early onset and high penetrance. Neoplastic progression is preceded by a chronic inflammation of the colon that resembles human inflammatory bowel disease and is promoted by the commensal microbiota. This study demonstrates that inflammation-associated colon carcinogenesis can be initiated and promoted solely by an intrinsic intestinal permeability barrier perturbation, establishes St14 as a critical tumor-suppressor gene in the mouse gastrointestinal tract and adds matriptase to the expanding list of pericellular proteases with tumor-suppressive functions. Oncogene (2012) 31, 3679-3695; doi:10.1038/onc.2011.545; published online 5 December 2011
C1 [Bugge, T. H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, Natl Inst Hlth, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU NIDCR Intramural Research Program
FX We thank Drs Jerrold M Ward, Robert D Cardiff and Stephen M Hewitt for
pathology advice, Drs Vyomesh Patel and Kantima Leelahavanichkul for
help with the array analysis, Dr Myrna Mandel for helicobacter testing,
as well as Drs Silvio Gutkind and Mary Jo Danton for critically
reviewing this manuscript. Histology was performed by Histoserv Inc.
(Germantown, MD, USA). This study was supported by the NIDCR Intramural
Research Program (THB).
NR 75
TC 15
Z9 16
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD AUG
PY 2012
VL 31
IS 32
BP 3679
EP 3695
DI 10.1038/onc.2011.545
PG 17
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 990TF
UT WOS:000307653800003
PM 22139080
ER
PT J
AU Udoetuk, JD
Dai, Y
Ying, GS
Daniel, E
Gangaputra, S
Rosenbaum, JT
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Kempen, JH
AF Udoetuk, Joshua D.
Dai, Yang
Ying, Gui-Shuang
Daniel, Ebenezer
Gangaputra, Sapna
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Kempen, John H.
CA Systemic Immunosuppressive Therapy
TI Risk of Corticosteroid-Induced Hyperglycemia Requiring Medical Therapy
among Patients with Inflammatory Eye Diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID INDUCED DIABETES-MELLITUS; PREVALENCE; GLUCOCORTICOIDS; MANAGEMENT;
UVEITIS
AB Objective: To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases.
Design: Retrospective cohort study.
Participants: Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications.
Methods: Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors.
Main Outcome Measures: Initiation of hypoglycemic medications.
Results: Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68-11.5). The RR tended to be higher in association with higher initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08-9.64; for initial prednisone dose >= 40 mg/d: RR, 5.51; 95% CI, 2.01-15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007).
Conclusions: These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:1569-1574 (C) 2012 by the American Academy of Ophthalmology.
C1 [Kempen, John H.] Univ Penn, Sch Med, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Udoetuk, Joshua D.; Dai, Yang; Ying, Gui-Shuang; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Ying, Gui-Shuang; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Udoetuk, Joshua D.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
[Daniel, Ebenezer; Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Gangaputra, Sapna; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
RP Kempen, JH (reprint author), Univ Penn, Sch Med, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316
FU National Eye Institute [EY014943]; Research to Prevent Blindness; Paul
and Evanina Mackall Foundation; R.P.B. James S. Adams Special Scholar
Award; R.P.B. Harrington Special Scholar Award; Department of Veterans'
Affairs
FX Supported primarily by National Eye Institute Grant EY014943 (J.H.K.).
Additional support was provided by Research to Prevent Blindness and the
Paul and Evanina Mackall Foundation. J.H.K. was an R.P.B. James S. Adams
Special Scholar Award recipient, J.E.T. was an R.P.B. Harrington Special
Scholar Award recipient, and D.A.J. and J.T.R. were Research to Prevent
Blindness Senior Scientific Investigator Award recipients during the
course of the study. G. A. L.-C. was previously supported by and R.B.N.
continues to be supported by intramural funds of the National Eye
Institute. E. B. S. receives support from the Department of Veterans'
Affairs. None of the sponsors had any role in the design and conduct of
the report; collection, management, analysis, and interpretation of the
data; or in the preparation, review, and approval of this manuscript.
NR 13
TC 5
Z9 5
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2012
VL 119
IS 8
BP 1569
EP 1574
DI 10.1016/j.ophtha.2012.01.043
PG 6
WC Ophthalmology
SC Ophthalmology
GA 982YA
UT WOS:000307080100012
PM 22484116
ER
PT J
AU Sood, BG
Shankaran, S
Schelonka, RL
Saha, S
Benjamin, DK
Sanchez, PJ
Adams-Chapman, I
Stoll, BJ
Thorsen, P
Skogstrand, K
Ehrenkranz, RA
Hougaard, DM
Goldberg, RN
Tyson, JE
Das, A
Higgins, RD
Carlo, WA
AF Sood, Beena G.
Shankaran, Seetha
Schelonka, Robert L.
Saha, Shampa
Benjamin, Danny K., Jr.
Sanchez, Pablo J.
Adams-Chapman, Ira
Stoll, Barbara J.
Thorsen, Poul
Skogstrand, Kristin
Ehrenkranz, Richard A.
Hougaard, David M.
Goldberg, Ronald N.
Tyson, Jon E.
Das, Abhik
Higgins, Rosemary D.
Carlo, Waldemar A.
CA Eunice Kennedy Shriver Natl Inst
TI Cytokine profiles of preterm neonates with fungal and bacterial sepsis
SO PEDIATRIC RESEARCH
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; BIRTH-WEIGHT INFANTS;
LATE-ONSET SEPSIS; EARLY-DIAGNOSIS; INFLAMMATORY MARKERS; IL-17
RECEPTOR; HOST-DEFENSE; FACTOR-ALPHA; TH17 CELLS
AB BACKGROUND: Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS).
METHODS: In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined-FS (>= 1 episode of FS), BS (>= 1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3 +/- 1, 7 +/- 2, 14 +/- 3, and 21 +/- 3 and sepsis group was explored.
RESULTS: Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-gamma (IFN-gamma), interleukin (IL)-10, IL-18, transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) (P < 0.05).
CONCLUSION: Significant differences in profiles for IFN-gamma, IL-10, IL-18, TGF-beta,and TNF-alpha in FS, BS,or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.
C1 [Sood, Beena G.; Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Schelonka, Robert L.; Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Saha, Shampa; Hougaard, David M.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Benjamin, Danny K., Jr.; Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Adams-Chapman, Ira; Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Thorsen, Poul] Lillebaelt Hosp, Dept Obstet & Gynecol, Kolding, Denmark.
[Skogstrand, Kristin] Statens Serum Inst, Dept Clin Biochem & Immunol, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Sood, BG (reprint author), Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
EM bsood@med.wayne.edu
OI Skogstrand, Kristin/0000-0002-0026-3711
FU National Institutes of Health (General Clinical Research Center) [M01
RR30, M01 RR32, M01 RR39, M01 RR70, M01 RR80, M01 RR633, M01 RR750, M01
RR997, M01 RR6022, M01 RR7122, M01 RR8084, M01 RR16587]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
[U10 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10
HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10
HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD40461, U10
HD40492, U10 HD40498, U10 HD40689]; U.S. Centers for Disease Control and
Prevention [Y1-HD-5000-01]; Thrasher Research Fund; NICHD [HD44799]
FX The National Institutes of Health (General Clinical Research Center
grants M01 RR30, M01 RR32, M01 RR39, M01 RR70, M01 RR80, M01 RR633, M01
RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, and M01 RR16587),
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) (grants U10 HD36790, U10 HD21364, U10 HD21373, U10
HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10
HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10
HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40689), and the
U.S. Centers for Disease Control and Prevention (Interagency Agreement
Y1-HD-5000-01) provided grant support for the Neonatal Research
Network's Cytokines Study. In addition, D.K.B. received support from the
Thrasher Research Fund and NICHD (Grant HD44799). The funding agencies
provided overall oversight for study conduct, but all data analyses and
interpretation were independent of the funding agencies. Information
regarding investigator/agency participation can be found in the
Supplementary Data online.
NR 45
TC 9
Z9 11
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
EI 1530-0447
J9 PEDIATR RES
JI Pediatr. Res.
PD AUG
PY 2012
VL 72
IS 2
BP 212
EP 220
DI 10.1038/pr.2012.56
PG 9
WC Pediatrics
SC Pediatrics
GA 979YY
UT WOS:000306862000014
PM 22562288
ER
PT J
AU Elkind, MM
Sutton, H
AF Elkind, M. M.
Sutton, Harriet
TI Radiation Response of Mammalian Cells Grown in Culture I. Repair of
X-Ray Damage in Surviving Chinese Hamster Cells
SO RADIATION RESEARCH
LA English
DT Article
ID LONG-TERM CULTIVATION; TISSUE CULTURE; INVITRO; STRAIN; PROTEIN; YEAST
C1 [Elkind, M. M.; Sutton, Harriet] NCI, NIH, Bethesda, MD 20892 USA.
RP Elkind, MM (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 25
TC 0
Z9 0
U1 1
U2 5
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD AUG
PY 2012
VL 178
IS 2
BP AV8
EP AV26
DI 10.1667/RRAV02.1
PG 19
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 981PZ
UT WOS:000306983000003
PM 22870981
ER
PT J
AU Preston, DL
Shimizu, Y
Pierce, DA
Suyama, A
Mabuchi, K
AF Preston, Dale L.
Shimizu, Yukiko
Pierce, Donald A.
Suyama, Akihiko
Mabuchi, Kiyohiko
TI Studies of Mortality of Atomic Bomb Survivors. Report 13: Solid Cancer
and Noncancer Disease Mortality: 1950-1997
SO RADIATION RESEARCH
LA English
DT Article
ID NUCLEAR INDUSTRY WORKERS; B SURFACE-ANTIGEN; BREAST-CANCER;
IONIZING-RADIATION; MYOCARDIAL-INFARCTION; TUBERCULOSIS PATIENTS;
FLUOROSCOPY COHORT; GENERAL MUTAGENS; HODGKINS-DISEASE; POOLED ANALYSIS
AB Preston, D. L., Shimizu, Y., Pierce, D. A., Suyama, A. and Mabuchi, K. Studies of Mortality of Atomic Bomb Survivors. Report 13: Solid Cancer and Noncancer Disease Mortality: 1950-1997. Radiat. Res. 160, 381-407 (2003).
This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings. (C) 2003 by Radiation Research Society
C1 [Preston, Dale L.] Radiat Effects Res Fdn, Dept Stat, Minami Ku, Hiroshima 7320815, Japan.
[Shimizu, Yukiko; Mabuchi, Kiyohiko] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 7320815, Japan.
[Suyama, Akihiko] Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan.
[Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Preston, DL (reprint author), Radiat Effects Res Fdn, Dept Stat, Minami Ku, 5-2 Hijiyama Koen, Hiroshima 7320815, Japan.
EM preston@ref.or.jp
FU Japanese Ministry of Health, Labour and Welfare; U.S. Department of
Energy through the National Academy of Sciences
FX The authors would like to thank H. Moriwaki, M. Hayashi, M. Konda and S.
Funamoto for help with data preparation, E. Grant for development of
data access tools that greatly facilitated this work, and the members of
the RERF Master File section for their diligent efforts to provide
accurate and timely data on mortality in the LSS and other RERF cohorts.
This publication is based on research performed at the Radiation Effects
Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a
private nonprofit foundation funded equally by the Japanese Ministry of
Health, Labour and Welfare and the U.S. Department of Energy through the
National Academy of Sciences.
NR 87
TC 16
Z9 16
U1 1
U2 7
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD AUG
PY 2012
VL 178
IS 2
BP AV146
EP AV172
DI 10.1667/RRAV12.1
PG 27
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 981PZ
UT WOS:000306983000013
PM 22870966
ER
PT J
AU Ron, E
Lubin, JH
Shore, RE
Mabuchi, K
Modan, B
Pottern, LM
Schneider, AB
Tucker, MA
Boice, JD
AF Ron, Elaine
Lubin, Jay H.
Shore, Roy E.
Mabuchi, Kiyohiko
Modan, Baruch
Pottern, Linda M.
Schneider, Arthur B.
Tucker, Margaret A.
Boice, John D., Jr.
TI Thyroid Cancer after Exposure to External Radiation: A Pooled Analysis
of Seven Studies
SO RADIATION RESEARCH
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; CHILDHOOD IRRADIATION; RETROSPECTIVE COHORT; NECK
IRRADIATION; SKIN HEMANGIOMA; TINEA CAPITIS; THYMUS GLAND; INDUCED HEAD;
FOLLOW-UP; NEOPLASMS
AB Ron, E., Lubin, J. H., Shore, R. E., Mabuchi, K., Modan, B., Pottern, L. M., Schneider, A. B., Tucker, M. A. and Boice, J. D., Jr. Thyroid Cancer after Exposure to External Radiation: A Pooled Analysis of Seven Studies. Radial. Res. 178, 43-60 (2012).
The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (>10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 104 PY Gy (EAR/104 PY Gy) was 4.4(95% CI=1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P=0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to >1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk at about 0.10 Gy. (C) 1995 by Radiation Research Society
C1 [Ron, Elaine; Lubin, Jay H.; Pottern, Linda M.; Tucker, Margaret A.; Boice, John D., Jr.] NCI, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA.
[Shore, Roy E.] NYU Med Ctr, Dept Environm Med, New York, NY 10010 USA.
[Mabuchi, Kiyohiko] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 732, Japan.
[Mabuchi, Kiyohiko] Radiat Effects Res Fdn, Dept Epidemiol Pathol, Hiroshima 732, Japan.
[Modan, Baruch] Chaim Sheba Med Ctr, Dept Clin Epidemiol, IL-52621 Tel Hashomer, Israel.
[Schneider, Arthur B.] Univ Illinois, Michael Reese Hosp, Dept Endocrinol & Metab, Chicago, IL 60616 USA.
RP Ron, E (reprint author), NCI, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
FU Japanese Ministry of Health and Welfare; United States Department of
Energy through the National Academy of Sciences
FX We would like to thank the Late Effects Study Group and the
International Radiation Study of Cervical Cancer Patients Group for
providing their data. We also wish to thank Tom Heide, Ed Hock and Dave
Hacker for their help in managing the data. The atomic bomb survivor
data were provided by the Radiation Effects Research Foundation, a
private nonprofit foundation funded equally by the Japanese Ministry of
Health and Welfare and the United States Department of Energy through
the National Academy of Sciences.
NR 55
TC 14
Z9 17
U1 5
U2 17
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD AUG
PY 2012
VL 178
IS 2
BP AV43
EP AV60
DI 10.1667/RRAV05.1
PG 18
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 981PZ
UT WOS:000306983000006
PM 22870979
ER
PT J
AU Ji, JF
Wang, XW
AF Ji, Junfang
Wang, Xin Wei
TI Clinical Implications of Cancer Stem Cell Biology in Hepatocellular
Carcinoma
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID TUMOR-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; HUMAN LIVER-CANCER;
HEPATIC PROGENITOR CELLS; SIDE POPULATION CELLS; STEM/PROGENITOR CELLS;
GENE-EXPRESSION; MOLECULAR PATHOGENESIS; ABCG2 EXPRESSION;
POOR-PROGNOSIS
C1 [Ji, Junfang; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Ji, JF (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Center for Cancer Research; National Cancer Institute [Z01 BC 010876]
FX The authors thank Karen Yarrick for bibliographic assistance. We regret
that we could not cite many important original papers because of space
limitations. This work was supported by the Intramural Research Program
of the Center for Cancer Research, the National Cancer Institute (Z01 BC
010876).
NR 88
TC 78
Z9 87
U1 1
U2 30
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2012
VL 39
IS 4
BP 461
EP 472
DI 10.1053/j.seminoncol.2012.05.011
PG 12
WC Oncology
SC Oncology
GA 987PO
UT WOS:000307429800010
PM 22846863
ER
PT J
AU So, R
Sasai, H
Matsuo, T
Tsujimoto, T
Eto, M
Saotome, K
Tanaka, K
AF So, Rina
Sasai, Hiroyuki
Matsuo, Tomoaki
Tsujimoto, Takehiko
Eto, Miki
Saotome, Kousaku
Tanaka, Kiyoji
TI Visceral Adipose Tissue Volume Estimated at Imaging Sites 5-6 cm Above
L4-L5 Is Optimal for Predicting Cardiovascular Risk Factors in Obese
Japanese Men
SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
DE cardiovascular disease; exercise; measurement site; multiple-slice
image; visceral adipose tissue
ID SINGLE-SLICE AREAS; METABOLIC SYNDROME; INSULIN-RESISTANCE;
INTRAABDOMINAL FAT; ABDOMINAL FAT; DISEASE; WOMEN; ASSOCIATION; EXERCISE
AB The association between visceral adipose tissue (VAT) with cardiovascular disease (CVD) has been clearly demonstrated. Although typical VAT area at 4th and 5th lumbar vertebrae (L4-L5) is used to approximate VAT volume, growing evidence has suggested that this measurement site may not be ideal. However, these findings for Asian people remain unclear. Thus, we searched for the better VAT measurement sites associated with CVD risk factors in obese, Japanese men. Eighty-two obese men were included in a cross-sectional study. Among these participants, 37 men completed the 12-week intervention (90 min and 3 d/week) were used for addressing longitudinal association between the VAT measurement sites and CVD risk factors. Consecutive MRI images (from 3 cm below L4-L5 to 20 cm above L4-L5) were used to explore the relationship between each VAT area and CVD risk factors (total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and blood pressure). The images located only 5-9 cm above L4-L5 had significant correlations with HDL cholesterol and triglycerides, but L4-L5 site did not in the cross-sectional analysis. In response to exercise, the image located 5 cm above L4-L5 showed the highest correlations with changes in total cholesterol (r = 0.46) and glucose (r = 0.36). Also, the image located 6 cm above L4-L5 showed highest correlations with changes in triglycerides (r = 0.37) and insulin (r = 0.37). Thus, the range of VAT images located 5-6 cm above L4-L5 may be optimal for identifying CVD risk factors compared to a typical site of L4-L5.
C1 [So, Rina; Matsuo, Tomoaki; Tsujimoto, Takehiko] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan.
[So, Rina] Japan Soc Promot Sci, Tokyo, Japan.
[Sasai, Hiroyuki] NIH, Bethesda, MD 20892 USA.
[Eto, Miki; Tanaka, Kiyoji] Univ Tsukuba, Fac Hlth & Sport Sci, Tsukuba, Ibaraki, Japan.
[Saotome, Kousaku] Univ Tsukuba, Ctr Cybern Res, Tsukuba, Ibaraki, Japan.
RP So, R (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan.
EM rina@stat.taiiku.tsukuba.ac.jp
OI Sasai, Hiroyuki/0000-0001-8120-6163
FU Funding Program for World-Leading Innovative R&D on Science and
Technology (First Program); Japan Society for the Promotion of Science
(JSPS) [23650429]
FX This study was supported by the Funding Program for World-Leading
Innovative R&D on Science and Technology (First Program) and the Japan
Society for the Promotion of Science (JSPS) #23650429.
NR 35
TC 5
Z9 6
U1 0
U2 1
PU TOHOKU UNIV MEDICAL PRESS
PI SENDAI
PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN
SN 0040-8727
EI 1349-3329
J9 TOHOKU J EXP MED
JI Tohoku J. Exp. Med.
PD AUG
PY 2012
VL 227
IS 4
BP 297
EP 305
DI 10.1620/tjem.227.297
PG 9
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 988XD
UT WOS:000307523900008
PM 22850595
ER
PT J
AU Dai, CL
Yao, XL
Keeran, KJ
Zywicke, GJ
Qu, X
Yu, ZX
Dagur, PK
McCoy, JP
Remaley, AT
Levine, SJ
AF Dai, Cuilian
Yao, Xianglan
Keeran, Karen J.
Zywicke, Gayle J.
Qu, Xuan
Yu, Zu-Xi
Dagur, Pradeep K.
McCoy, J. Philip
Remaley, Alan T.
Levine, Stewart J.
TI Apolipoprotein A-I Attenuates Ovalbumin-Induced Neutrophilic Airway
Inflammation via a Granulocyte Colony-Stimulating Factor-Dependent
Mechanism
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE airway inflammation; ovalbumin; neutrophil; apolipoprotein A-I; G-CSF
ID CELL-ADHESION MOLECULE-1; ACUTE LUNG INJURY; UP-REGULATION;
ENDOTHELIAL-CELLS; MIMETIC PEPTIDE; MESSENGER-RNA; ASTHMA; MICE;
LIPOPOLYSACCHARIDE; DISEASE
AB Apolipoprotein A-I (apoA-I) is a key component of high-density lipoproteins that mediates reverse cholesterol transport from cells and reduces vascular inflammation. We investigated whether endogenous apoA-I modulates ovalbumin (OVA)-induced airway inflammation in mice. We found that apoA-I expression was significantly reduced in the lungs of OVA-challenged, compared with saline-challenged, wild-type (WT) mice. Next, to investigate the role of endogenous apoA-I in the pathogenesis of OVA-induced airway inflammation, WT and apoA-I-/- mice were sensitized by intraperitoneal injections of OVA and aluminum hydroxide, followed by multiple nasal OVA challenges for 4 weeks. OVA-challenged apoA-I-/- mice exhibited a phenotype of increased airway neutrophils compared with WT mice, which could be rescued by an administration of a 5A apoA-I mimetic peptide. Multiple pathways promoted neutrophilic inflammation in OVA-challenged apoA-I-/- mice, including the up-regulated expression of (1) proinflammatory cytokines (IL-17A and TNF-alpha), (2) CXC chemokines (CXCL5), (3) vascular adhesion molecules (i.e., vascular cell adhesion molecule-1), and (4) granulocyte colony-stimulating factors (G-CSF). Because concentrations of G-CSF in bronchoalveolar lavage fluid (BALF) were markedly increased in OVA-challenged apoA-I-/- mice, we hypothesized that enhanced G-CSF expression may represent the predominant pathway mediating increased neutrophilic inflammation. This was confirmed by the intranasal administration of a neutralizing anti-G-CSF antibody, which significantly reduced BALF neutrophilia by 72% in OVA-challenged apoA-I-/- mice, compared with mice that received a control antibody. We conclude that endogenous apoA-I negatively regulates OVA-induced neutrophilic airway inflammation, primarily via a G-CSF-dependent mechanism. Furthermore, these findings suggest that apoA-I may play an important role in modulating the severity of neutrophilic airway inflammation in asthma.
C1 [Dai, Cuilian; Yao, Xianglan; Remaley, Alan T.; Levine, Stewart J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Keeran, Karen J.; Zywicke, Gayle J.] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA.
[Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA.
[Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health; National Institutes of Health
grant [1ZIAHL006053-02]
FX This work was supported by the Division of Intramural Research, National
Heart, Lung, and Blood Institute, National Institutes of Health, and by
National Institutes of Health grant 1ZIAHL006053-02 (S.J.L.).
NR 51
TC 20
Z9 20
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD AUG
PY 2012
VL 47
IS 2
BP 186
EP 195
DI 10.1165/rcmb.2011-0322OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 986SQ
UT WOS:000307365300007
PM 22427535
ER
PT J
AU Yazdanyar, A
Wasko, MC
Kraemer, KL
Ward, MM
AF Yazdanyar, Ali
Wasko, Mary Chester
Kraemer, Kevin L.
Ward, Michael M.
TI Perioperative all-cause mortality and cardiovascular events in patients
with rheumatoid arthritis: Comparison with unaffected controls and
persons with diabetes mellitus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID C-REACTIVE PROTEIN; RISK-FACTORS; CARDIAC RISK; NONCARDIAC SURGERY;
CORONARY-DISEASE; MEDICAL-RECORD; PREDICTION; COHORT; ATHEROSCLEROSIS;
INFLAMMATION
AB Objective Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) burden similar to that of diabetes mellitus (DM). This risk may warrant preoperative CV assessment as is performed for patients with DM. We aimed to determine whether the risks of perioperative death and CV events among patients with RA differed from those among unaffected controls and patients with DM. Methods We used 19982002 data from the Nationwide Inpatient Sample (NIS) database of the Healthcare Cost Utilization Project (HCUP) to identify hospitalizations of patients undergoing elective noncardiac surgery. Using established guidelines, surgical procedures were categorized as either low risk, intermediate risk, or high risk of having CV events. Logistic models provided the adjusted odds of study end points in patients with RA, DM, or both relative to patients with neither condition. Results Among 7,756,570 patients undergoing a low-risk, intermediate-risk, or high-risk noncardiac procedure, 2.34%, 0.51%, and 2.12%, respectively, had a composite CV event, and death occurred in 1.47%, 0.50%, and 2.59%, respectively. Among those undergoing an intermediate-risk procedure, death was less likely in RA patients than in DM patients (0.30% versus 0.65%; P < 0.001), but the difference in mortality rates among those undergoing low-risk versus high-risk procedures was not significant. Patients with RA were less likely to have a CV event than were patients with DM for procedures of low risk (3.38% versus 5.30%; P < 0.001) and intermediate risk (0.34% versus 1.07%; P < 0.001). In adjusted models, RA was not independently associated with an increased risk of perioperative death or a CV event. Conclusion RA was not associated with adverse perioperative CV risk or mortality risk, which suggests that current perioperative clinical care does not need to be changed in this regard.
C1 [Yazdanyar, Ali] Reading Hosp Med Ctr, Sect Hosp Med, Dept Med, W Reading, PA 19612 USA.
[Wasko, Mary Chester] W Penn Allegheny Hlth Syst, Pittsburgh, PA USA.
[Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Yazdanyar, A (reprint author), Reading Hosp Med Ctr, Sect Hosp Med, Dept Med, 6th Ave & Spruce St, W Reading, PA 19612 USA.
EM a.yazzzd@gmail.com
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, NIH; Centocor
FX Supported in part by the Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH.; Dr.
Wasko has received consulting fees from Centocor (less than $10,000).
NR 34
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2012
VL 64
IS 8
BP 2429
EP 2437
DI 10.1002/art.34428
PG 9
WC Rheumatology
SC Rheumatology
GA 980PX
UT WOS:000306906500003
PM 22354534
ER
PT J
AU Goker-Alpan, O
Masdeu, JC
Kohn, PD
Ianni, A
Lopez, G
Groden, C
Chapman, MC
Cropp, B
Eisenberg, DP
Maniwang, ED
Davis, J
Wiggs, E
Sidransky, E
Berman, KF
AF Goker-Alpan, Ozlem
Masdeu, Joseph C.
Kohn, Philip D.
Ianni, Angela
Lopez, Grisel
Groden, Catherine
Chapman, Molly C.
Cropp, Brett
Eisenberg, Daniel P.
Maniwang, Emerson D.
Davis, Joie
Wiggs, Edythe
Sidransky, Ellen
Berman, Karen F.
TI The neurobiology of glucocerebrosidase-associated parkinsonism: a
positron emission tomography study of dopamine synthesis and regional
cerebral blood flow
SO BRAIN
LA English
DT Article
DE brain imaging; genetic risk; positron emission tomography (PET);
Parkinson disease; lysosomal storage disorders
ID GAUCHER-DISEASE; F-18-DOPA PET; MUTATIONS; DYSFUNCTION; PROGRESSION;
DEMENTIA; CARRIERS; RISK; GENE; LEWY
AB Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls. Patients with GBA mutations generally have an earlier onset of Parkinson disease and more cognitive impairment than those without GBA mutations. We investigated whether GBA mutations alter the neurobiology of Parkinson disease, studying brain dopamine synthesis and resting regional cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine synthesis with F-18-fluorodopa positron emission tomography, and resting regional cerebral blood flow with (H2O)-O-15 positron emission tomography in the wakeful, resting state in four study groups: (i) patients with Parkinson disease and Gaucher disease (n = 7, average age = 56.6 +/- 9.2 years); (ii) patients with Parkinson disease without GBA mutations (n = 11, 62.1 +/- 7.1 years); (iii) patients with Gaucher disease without parkinsonism, but with a family history of Parkinson disease (n = 14, 52.6 +/- 12.4 years); and (iv) healthy GBA-mutation carriers with a family history of Parkinson disease (n = 7, 50.1 +/- 18 years). We compared each study group with a matched control group. Data were analysed with region of interest and voxel-based methods. Disease duration and Parkinson disease functional and staging scores were similar in the two groups with parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction in the caudate (20 and 18% loss). However, the group with both Parkinson and Gaucher diseases showed decreased resting regional cerebral blood flow in the lateral parieto-occipital association cortex and precuneus bilaterally. Furthermore, two subjects with Gaucher disease without parkinsonian manifestations showed diminished striatal dopamine. In conclusion, the pattern of dopamine loss in patients with both Parkinson and Gaucher disease was similar to sporadic Parkinson disease, indicating comparable damage in midbrain neurons. However, (H2O)-O-15 positron emission tomography studies indicated that these subjects have decreased resting activity in a pattern characteristic of diffuse Lewy body disease. These findings provide insight into the pathophysiology of GBA-associated parkinsonism.
C1 [Goker-Alpan, Ozlem; Lopez, Grisel; Groden, Catherine; Maniwang, Emerson D.; Davis, Joie; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Masdeu, Joseph C.; Kohn, Philip D.; Ianni, Angela; Chapman, Molly C.; Cropp, Brett; Eisenberg, Daniel P.; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Wiggs, Edythe] NINDS, Off Clin Director, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), 35 Convent Dr,Room 1A213, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
RI Eisenberg, Daniel/C-7432-2014; Eisenberg, Daniel/S-4342-2016
FU National Institute of Mental Health; National Human Genome Research
Institute, National Institutes of Health
FX Funding was provided by the Intramural Research Programs of the National
Institute of Mental Health and National Human Genome Research Institute,
National Institutes of Health.
NR 39
TC 33
Z9 33
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD AUG
PY 2012
VL 135
BP 2440
EP 2448
DI 10.1093/brain/aws174
PN 8
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 984DQ
UT WOS:000307170300023
PM 22843412
ER
PT J
AU Schlichting, JA
Soliman, AS
Schairer, C
Schottenfeld, D
Merajver, SD
AF Schlichting, Jennifer A.
Soliman, Amr S.
Schairer, Catherine
Schottenfeld, David
Merajver, Sofia D.
TI Inflammatory and non-inflammatory breast cancer survival by
socioeconomic position in the Surveillance, Epidemiology, and End
Results database, 1990-2008
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Inflammatory breast cancer; Socioeconomic position; Epidemiology; Breast
cancer-specific survival
ID CONSERVATION SURGERY; CARCINOMA INCIDENCE; AFRICAN-AMERICAN; RESULTS
PROGRAM; UNITED-STATES; BLACK-WOMEN; DISPARITIES; DIAGNOSIS; STAGE; RACE
AB Although it has been previously reported that patients with inflammatory breast cancer (IBC) experience worse survival than patients with other breast cancer (BC) types, the socioeconomic and ethnic factors leading to this survival difference are not fully understood. The association between county-level percent of persons below the poverty level and BC-specific (BCS) survival for cases diagnosed from 1990 to 2008 in the Surveillance, Epidemiology, and End Results (SEER) database linked to census derived county attributes was examined. A sub-analysis of cases from 2000 to 2008 also examined BCS survival by an index combining percent below poverty and less than high school graduates as well as metropolitan versus non-metropolitan county of residence. The Kaplan-Meier estimator was used to construct survival curves by stage, inflammatory status, and county-level socioeconomic position (SEP). Stage and inflammatory status stratified proportional hazards models, adjusted for age, race/ethnicity, tumor and treatment characteristics were used to determine the hazard of BCS death by county-level SEP. Kaplan-Meier survival curves indicated IBC has worse survival than stage matched non-IBC, (stage III IBC median survival = 4.75 years vs. non-IBC = 13.4 years, p < 0.0001). Residing in a lower SEP, non-metro county significantly worsens BCS survival for non-IBC in multivariate proportional hazards models. African American cases appear to have worse survival than non-Hispanic Whites regardless of inflammatory status, stage, county-level SEP, tumor, or treatment characteristics. This is the first study to examine IBC survival by SEP in a nation-wide population-based tumor registry. As this analysis found generally poorer survival for IBC, regardless of SEP or race/ethnicity, it is important that interventions that help educate women on IBC symptoms target women in various SEP and race/ethnicity groups.
C1 [Schlichting, Jennifer A.; Soliman, Amr S.; Schottenfeld, David; Merajver, Sofia D.] Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Schairer, Catherine] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Schottenfeld, David; Merajver, Sofia D.] Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA.
[Merajver, Sofia D.] Univ Michigan, Ctr Global Hlth, Ann Arbor, MI 48104 USA.
RP Schlichting, JA (reprint author), Univ Michigan, Dept Epidemiol, Sch Publ Hlth, 109 Observ St, 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 The authors thank Dr. William Anderson at the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, for providing
expertise on IBC and the SEER database, as well as the merged
race-ethnicity and stage SEER*stat variables used in this analysis. This
work was supported by a Rackham Merit Fellowship (JAS) 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 (AS and SDM),
the Breast Cancer Research Foundation (SDM), and the Debbie
Strange-Browne Inflammatory Breast Cancer Foundation (SDM).
NR 72
TC 7
Z9 8
U1 0
U2 7
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 AUG
PY 2012
VL 134
IS 3
BP 1257
EP 1268
DI 10.1007/s10549-012-2133-2
PG 12
WC Oncology
SC Oncology
GA 985NL
UT WOS:000307273300034
PM 22733221
ER
PT J
AU Dallal, CM
Brinton, LA
Matthews, CE
Lissowska, J
Peplonska, B
Hartman, TJ
Gierach, GL
AF Dallal, Cher M.
Brinton, Louise A.
Matthews, Charles E.
Lissowska, Jolanta
Peplonska, Beata
Hartman, Terryl J.
Gierach, Gretchen L.
TI Accelerometer-based measures of active and sedentary behavior in
relation to breast cancer risk
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Physical activity; Sedentary behavior; Objective measures
ID PHYSICAL-ACTIVITY LEVELS; US ADULTS; EPIDEMIOLOGIC EVIDENCE; BIOLOGIC
MECHANISMS; NHANES 2003-2006; TIME SPENT; PREVENTION; ASSOCIATIONS;
BIOMARKERS; HEALTH
AB Epidemiologic studies suggest that physical activity reduces breast cancer risk by 20-40 %. However, prior studies have relied on measures of self-report. In a population-based case-control study, we evaluated accelerometer measures of active and sedentary behavior in relation to breast cancer among 996 incident cases and 1,164 controls, residents of Warsaw, Poland (2000-2003), who were asked to wear an accelerometer for 7 days. Accelerometer values were averaged across valid wear days and summarized as overall activity (counts [ct]/min/day); in minutes spent in sedentary behavior (0-99 ct/min); and light (100-759 ct/min) and moderate-to-vigorous (760+ ct/min) activity. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression. Comparing women in the highest quartile (Q4) of activity to those in the lowest (Q1), time spent in moderate-to-vigorous activity was inversely associated with breast cancer odds after adjustment for known risk factors, sedentary behavior and wear time (ORQ4vsQ1 0.39, 95 % CI 0.27-0.56; P-trend < .0001). Sedentary time was positively associated with breast cancer, independent of moderate-to-vigorous activity (ORQ4vsQ1 1.81, 95 % CI 1.26-2.60; P-trend = 0.001). Light activity was not associated with breast cancer in multivariable models including both moderate-to-vigorous activity and sedentary behavior. Our findings support an inverse association between accelerometer-based measures of moderate-to-vigorous physical activity and breast cancer while also suggesting potential increases in risk with sedentary time.
C1 [Dallal, Cher M.; Brinton, Louise A.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Dallal, Cher M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, PL-02781 Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland.
[Peplonska, Beata] Nofer Inst Occupat Med, Dept Environm Epidemiol, PL-91348 Lodz, Poland.
[Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
RP Dallal, CM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550,Rm 5010, Bethesda, MD 20892 USA.
EM cher.dallal@nih.gov
RI Peplonska, Beata/F-6004-2010; matthews, Charles/E-8073-2015; Brinton,
Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016;
OI matthews, Charles/0000-0001-8037-3103; Brinton,
Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522;
Lissowska, Jolanta/0000-0003-2695-5799
FU National Cancer Institute, Department of Health and Human Services, USA
FX We thank Michael Stagner and Pei Chao for their work on study and data
management (IMS, Silver Spring, MD); physicians, pathologists, nurses,
and interviewers from participating centers in Poland for their efforts
in the field. We also thank the participants of the Polish Study for
their contributions to this study, Dr. Bill Anderson for his statistical
consultation, Dr. Mark Sherman for his independent evaluation of
histopathological information, and Drs. Montserrat Garcia-Closas and
Mark Sherman for contributions to study design. Polish Breast Cancer
Study was supported by the Intramural Research Program of the National
Cancer Institute, Department of Health and Human Services, USA.
Participating centers in Poland: Cancer Center and M. Sklodowska-Curie
Institute of Oncology in Warsaw Departments of Epidemiology
(Coordinating center: Dr Jolanta Lissowska, Mrs Alicja
Bardin-Mikolajczak, and Dr Witold Zatonski), Breast Cancer Treatment and
Reconstruction (Drs Edward Towpik and Jerzy Giermek), Departments of
Surgical Oncology (Dr Pawel Kukawski), and Pathology (Drs Grzegorz
Rymkiewicz, Marcin Ligaj, Joanna Baran'ska, Agnieszka Turowicz, and
Wlodzimierz Olszewski). Polish Oncological Foundation in Warsaw
Pathology (Drs Dorota Mazepa-Sikora, Wlodzimierz Olszewski). Nofer
Institute of Occupational Medicine in Lodz' (Drs Neonila
Szeszenia-Dabrowska, Beata Peplonska). Medical University in Lodz'
Oncology Clinic (Drs Arkadiusz Jeziorski, Janusz Piekarski), and
Pathology Department (Drs Radzislaw Kordek, Grazyna Pasz-Walczak, Robert
Kubiak, Dorota Kupnicka, Boguslaw Olborski). Community Copernicus
Hospital in Lodz' Department of Surgical Oncology (Drs Zbigniew Morawiec
and Mariusz Pawlak). Polish Mother's Health Memorial Hospital in Lodz'
Departments of Surgical Oncology and Breast Diseases (Drs Marcin Faflik,
Magdalena Baklinska, Marek Zadrozny, Boguslaw Westfal) and Clinical
Pathomorphology (Drs Stanislaw Lukaszek, Andrzej Kulig).
NR 26
TC 13
Z9 14
U1 1
U2 7
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 AUG
PY 2012
VL 134
IS 3
BP 1279
EP 1290
DI 10.1007/s10549-012-2129-y
PG 12
WC Oncology
SC Oncology
GA 985NL
UT WOS:000307273300036
PM 22752209
ER
PT J
AU Sheldon, LK
Leonard, K
Gross, A
Hartnett, E
Poage, E
Squires, J
Ullemeyer, V
Schueller, M
Stary, S
Miller, MA
AF Sheldon, Lisa Kennedy
Leonard, Kathleen
Gross, Anne
Hartnett, Erin
Poage, Ellen
Squires, Jennifer
Ullemeyer, Vicki
Schueller, Mary
Stary, Susan
Miller, Mary Alice
TI Oncology Nursing in Cuba: Report of the Delegation
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Editorial Material
AB In December 2011, the first delegation of oncology nurses from the United States visited Havana, Cuba. The delegation included oncology nurses, educators, and leaders from across America and provided opportunities to learn about the healthcare system, cancer, and oncology nursing in Cuba. Delegation members attended lectures, toured facilities, and enjoyed Cuban culture. This exchange highlighted the similarities in cancer care and oncology nursing between countries and opened doors for future collaborations.
C1 [Sheldon, Lisa Kennedy] Univ Massachusetts, Boston, MA 02125 USA.
[Leonard, Kathleen; Hartnett, Erin] NYU, Langone Med Ctr, New York, NY USA.
[Gross, Anne] Dana Farber Canc Inst, Boston, MA USA.
[Poage, Ellen] Rehabil Associates Naples, Ft Myers, FL USA.
[Squires, Jennifer] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Ullemeyer, Vicki] Novartis Pharmaceut, Ft Myers, FL USA.
[Schueller, Mary] St Nicholas Hosp, Sheboygan, WI USA.
[Stary, Susan] Univ Texas MD Anderson Phys Network, Houston, TX USA.
[Miller, Mary Alice] Permanente Med Grp Inc, San Rafael, CA USA.
RP Sheldon, LK (reprint author), Univ Massachusetts, Harbor Campus, Boston, MA 02125 USA.
EM lisa.kennedysheldon@umb.edu
OI Sheldon, Lisa Kennedy/0000-0002-5958-8529
NR 15
TC 1
Z9 1
U1 0
U2 1
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD AUG
PY 2012
VL 16
IS 4
BP 421
EP 424
DI 10.1188/12.CJON.421-424
PG 4
WC Oncology; Nursing
SC Oncology; Nursing
GA 981AL
UT WOS:000306937500017
PM 22842695
ER
PT J
AU Cawley, NX
AF Cawley, Niamh X.
TI Sugar Making Sugar: Gluconeogenesis Triggered by Fructose via a
Hypothalamic-Adrenal-Corticosterone Circuit
SO ENDOCRINOLOGY
LA English
DT Editorial Material
ID ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE; MALONYL-COA; FOOD-INTAKE;
GLUCOSE; RESPONSES; GLUCOCORTICOIDS; HYPOGLYCEMIA; BEVERAGES; INCREASE
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Cawley, NX (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, 49 Convent Dr,Room 5A22, Bethesda, MD 20892 USA.
EM cawleyn@mail.nih.gov
FU Intramural NIH HHS
NR 23
TC 2
Z9 2
U1 0
U2 3
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 AUG
PY 2012
VL 153
IS 8
BP 3561
EP 3563
DI 10.1210/en.2012-1562
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 977JD
UT WOS:000306652400003
PM 22822224
ER
PT J
AU Lannan, EA
Galliher-Beckley, AJ
Scoltock, AB
Cidlowski, JA
AF Lannan, Erica A.
Galliher-Beckley, Amy J.
Scoltock, Alyson B.
Cidlowski, John A.
TI Proinflammatory Actions of Glucocorticoids: Glucocorticoids and TNF
alpha Coregulate Gene Expression In Vitro and In Vivo
SO ENDOCRINOLOGY
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; PARKINSONS-DISEASE;
ALPHA-1-ANTICHYMOTRYPSIN POLYMORPHISM; ALPHA(1)-ANTICHYMOTRYPSIN
EXPRESSION; TRANSCRIPTION FACTORS; OSTEOSARCOMA CELLS; RECEPTOR;
MECHANISMS; INDUCE; SUSCEPTIBILITY
AB Synthetic glucocorticoids are widely used for treatment of many inflammatory diseases. However, long-term glucocorticoid treatment can cause a variety of negative side effects. A genome-wide microarray analysis was performed in human lung A549 cells to identify genes regulated by both the antiinflammatory steroid dexamethasone (Dex) and the proinflammatory cytokine TNF alpha. Unexpectedly, we discovered that numerous genes were coregulated by treatment with both Dex and TNF alpha. We evaluated the mechanism of coregulation of one of these genes, serpinA3 (alpha-1 antichymotrypsin), a secreted, acute phase protein strongly associated with numerous inflammatory diseases. Up-regulation of serpinA3 requires the presence of both the glucocorticoid receptor and TNF alpha soluble receptor 1. Treatment with Dex or TNF alpha resulted in a 10- to 25-fold increase of serpinA3 mRNA, whereas coadministration of Dex and TNF alpha led to a synergistic increase in serpinA3 mRNA. The naturally occurring glucocorticoid, cortisol, also resulted in a synergistic increase inserpinA3 mRNA levels in A549 cells. Furthermore, in vivo treatment of C57BL/6 mice with Dex and TNF alpha resulted in coregulation of serpinA3 mRNA levels in both lung and liver tissues. Finally, chromatin immunoprecipitation analyses suggest that glucocorticoid receptor binding to the serpinA3 transcriptional start site can be enhanced by the combination of Dex plus TNF alpha treatment of A549 cells. These studies demonstrate that glucocorticoids and proinflammatory compounds can coregulate genes associated with human disease. This discovery may underlie the basis of some of the adverse effects associated with long-term glucocorticoid therapy. (Endocrinology 153: 3701-3712, 2012)
C1 [Lannan, Erica A.; Galliher-Beckley, Amy J.; Scoltock, Alyson B.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU National Institutes of Health
FX This work was supported by National Institutes of Health intramural
funding.
NR 38
TC 34
Z9 34
U1 0
U2 6
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 AUG
PY 2012
VL 153
IS 8
BP 3701
EP 3712
DI 10.1210/en.2012-1020
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 977JD
UT WOS:000306652400018
PM 22673229
ER
PT J
AU Burns, KA
Rodriguez, KF
Hewitt, SC
Janardhan, KS
Young, SL
Korach, KS
AF Burns, Katherine A.
Rodriguez, Karina F.
Hewitt, Sylvia C.
Janardhan, Kyathanahalli S.
Young, Steven L.
Korach, Kenneth S.
TI Role of Estrogen Receptor Signaling Required for Endometriosis-Like
Lesion Establishment in a Mouse Model
SO ENDOCRINOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MATRIX-METALLOPROTEINASE EXPRESSION;
PERITONEAL-FLUID MACROPHAGES; ER-ALPHA; OVARIAN-STEROIDS;
GENE-EXPRESSION; MMP EXPRESSION; STROMAL CELLS; MURINE MODEL; B-ISOFORM
AB Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ER alpha and ER beta, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ER alpha-knockout (alpha ERKO), and beta ERKO mice were donors or recipients to investigate the roles of ER alpha, ER beta, and estradiol-mediated signaling on endometriosis-like disease. Mice were treated with vehicle or estradiol, and resulting location, number, and size of endometriosis-like lesions were assessed. In comparison with WT lesions in WT hosts, alpha ERKO lesions in WT hosts were smaller and fewer in number. The effect of ER status and estradiol treatment on nuclear receptor status, proliferation, organization, and inflammation within lesions were examined. alpha ERKO lesions in WT hosts did not form distal to the incision site, respond to estradiol, or proliferate but did have increased inflammation. WT lesions in alpha ERKO hosts did respond to estradiol, proliferate, and show decreased inflammation with treatment, but surprisingly, progesterone receptor expression and localization remained unchanged. Only minor differences were observed between WT lesions in beta ERKO hosts and beta ERKO lesions in WT hosts, demonstrating the estradiol-mediated signaling responses are predominately through ER alpha. In sum, these results suggest ER in both endometriosis-like lesions and their environment influence lesion characteristics, and understanding these interactions may play a critical role in elucidating this enigmatic disease. (Endocrinology 153: 3960-3971, 2012)
C1 [Burns, Katherine A.; Rodriguez, Karina F.; Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli S.] NIEHS, Comparat & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli S.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA.
[Young, Steven L.] Univ N Carolina, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA.
RP Korach, KS (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27790 USA.
EM Korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health [Z01ES70065]
FX This work was supported by National Institutes of Health Grant
Z01ES70065.
NR 65
TC 31
Z9 31
U1 0
U2 4
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 AUG
PY 2012
VL 153
IS 8
BP 3960
EP 3971
DI 10.1210/en.2012-1294
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 977JD
UT WOS:000306652400042
PM 22700766
ER
PT J
AU Bharti, N
Broutin, H
Grais, RF
Ferrari, MJ
Djibo, A
Tatem, AJ
Grenfell, BT
AF Bharti, N.
Broutin, H.
Grais, R. F.
Ferrari, M. J.
Djibo, A.
Tatem, A. J.
Grenfell, B. T.
TI Spatial dynamics of meningococcal meningitis in Niger: observed patterns
in comparison with measles
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Epidemiology; measles (rubeola); meningitis - bacterial; spatial
modelling; vaccine-preventable diseases
ID SUB-SAHARAN AFRICA; NEISSERIA-MENINGITIDIS; COMMUNITY SIZE;
BURKINA-FASO; SAUDI-ARABIA; DISEASE; EPIDEMICS; CARRIAGE; INFLUENZA;
TRANSMISSION
AB Throughout the African meningitis belt, meningococcal meningitis outbreaks occur only during the dry season. Measles in Niger exhibits similar seasonality, where increased population density during the dry season probably escalates measles transmission. Because meningococcal meningitis and measles are both directly transmitted, we propose that host aggregation also impacts the transmission of meningococcal meningitis. Although climate affects broad meningococcal meningitis seasonality, we focus on the less examined role of human density at a finer spatial scale. By analysing spatial patterns of suspected cases of meningococcal meningitis, we show fewer absences of suspected cases in districts along primary roads, similar to measles fadeouts in the same Nigerien metapopulation. We further show that, following periods during no suspected cases, districts with high reappearance rates of meningococcal meningitis also have high measles reintroduction rates. Despite many biological and epidemiological differences, similar seasonal and spatial patterns emerge from the dynamics of both diseases. This analysis enhances our understanding of spatial patterns and disease transmission and suggests hotspots for infection and potential target areas for meningococcal meningitis surveillance and intervention.
C1 [Bharti, N.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Bharti, N.; Grenfell, B. T.] Princeton Univ, Ctr Hlth & Wellbeing, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Broutin, H.] UM2, UM1, IRD 224, UMR CNRS 5290,MIVEGEC, Montpellier, France.
[Grais, R. F.] Epictr, Paris, France.
[Ferrari, M. J.] Penn State Univ, Dept Biol, Dept Stat, University Pk, PA 16802 USA.
[Ferrari, M. J.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Djibo, A.] Minist Hlth, Niamey, Niger.
[Tatem, A. J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, A. J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
[Broutin, H.; Tatem, A. J.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bharti, N (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
EM nbharti@princeton.edu
FU RAPIDD programme of the Science and Technology Directorate, Department
of Homeland Security; Fogarty International Center, National Institutes
of Health; Intramural Research Group at Fogarty International Center,
National Institutes of Health; Bill and Melinda Gates Foundation [49446]
FX This study was supported by the Bill and Melinda Gates Foundation.
M.J.F., A.J.T., and B.T.G. were also supported by the RAPIDD programme
of the Science and Technology Directorate, Department of Homeland
Security. B.T.G. was also supported by the Fogarty International Center,
National Institutes of Health. H.B. was supported by the Intramural
Research Group at Fogarty International Center, National Institutes of
Health. A.J.T. was also supported by a grant from the Bill and Melinda
Gates Foundation (no. 49446). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 5
Z9 5
U1 0
U2 25
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 AUG
PY 2012
VL 140
IS 8
BP 1356
EP 1365
DI 10.1017/S0950268811002032
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 980ZW
UT WOS:000306936000002
PM 22009033
ER
PT J
AU Emery, AC
Eiden, LE
AF Emery, Andrew C.
Eiden, Lee E.
TI Signaling through the neuropeptide GPCR PAC(1) induces neuritogenesis
via a single linear cAMP- and ERK-dependent pathway using a novel cAMP
sensor
SO FASEB JOURNAL
LA English
DT Article
DE adenylate cyclase; neurite; Neuroscreen-1; PC12; signal transduction
ID CYCLASE-ACTIVATING POLYPEPTIDE; PROTEIN-KINASE-A; NERVE GROWTH-FACTOR;
VASOACTIVE-INTESTINAL-PEPTIDE; PC12 CELLS; NEURITE OUTGROWTH; NEURONAL
DIFFERENTIATION; RAP1 ACTIVATION; GENE-EXPRESSION; CYCLIC-AMP
AB Both cAMP and ERK are necessary for neuroendocrine cell neuritogenesis, and pituitary adenylate cyclase-activating polypeptide (PACAP) activates each. It is important to know whether cAMP and ERK are arranged in a novel, linear pathway or in two parallel pathways using known signaling mechanisms. Native cellular responses [cAMP elevation, ERK phosphorylation, cAMP responsive element binding (CREB) phosphorylation, and neuritogenesis] and promoter-reporter gene activation after treatment with forskolin, cAMP analogs, and PACAP were measured in Neuroscreen-1 (NS-1) cells, a PC12 variant enabling simultaneous morphological, molecular biological, and biochemical analysis. Forskolin (25 mu M) and cAMP analogs (8-bromo-cAMP, dibutyryl-cAMP, and 8-chlorophenylthio-cAMP) stimulated ERK phosphorylation and neuritogenesis in NS-1 cells. Both ERK phosphorylation and neuritogenesis were MEK dependent (blocked by 10 mu M U0126) and PKA independent (insensitive to 30 mu M H-89 or 100 nM myristoylated protein kinase A inhibitor). CREB phosphorylation induced by PACAP was blocked by H-89. The exchange protein activated by cAMP (Epac)-selective 8-(4-chlorophenylthio)-2'-O-Me-cAMP (100-500 mu M) activated Rap1 without affecting the other cAMP-dependent processes. Thus, PACAP-38 potently stimulated two distinct and independent cAMP pathways leading to CREB or ERK activation in NS-1 cells. Drug concentrations for appropriate effect were derived from control data for all compounds. In summary, a novel PKA- and Epac-independent signaling pathway: PACAP -> adenylate cyclase -> cAMP -> ERK -> neuritogenesis has been identified.-Emery, A. C., Eiden, L. E. Signaling through the neuropeptide GPCR PAC(1) induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor. FASEB J. 26, 3199-3211 (2012). www.fasebj.org
C1 [Emery, Andrew C.; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, 49 Convent Dr,Bldg 49,Rm 5A-38, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU NIMH Intramural Research Project [1-Z01-MH002386]
FX The authors thank Dr. Tomris Mustafa [U.S. National Institute of Mental
Health (NIMH)] and Dr. Tamas Balla (Eunice Kennedy Shriver National
Institute of Child Health and Human Development) for their helpful
suggestions and feedback about this manuscript. All work performed was
supported by NIMH Intramural Research Project 1-Z01-MH002386. The
authors declare no conflicts of interest.
NR 56
TC 24
Z9 25
U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD AUG
PY 2012
VL 26
IS 8
BP 3199
EP 3211
DI 10.1096/fj.11-203042
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 984BI
UT WOS:000307162800011
PM 22532442
ER
PT J
AU Boutin, A
Allen, MD
Neumann, S
Gershengorn, MC
AF Boutin, Alisa
Allen, Michael D.
Neumann, Susanne
Gershengorn, Marvin C.
TI Persistent signaling by thyrotropin-releasing hormone receptors
correlates with G-protein and receptor levels
SO FASEB JOURNAL
LA English
DT Article
DE TRH receptor; inositolmonophosphate
ID COUPLED RECEPTORS; TRH RECEPTOR; FLUORESCENT PROTEIN; INVERSE AGONISTS;
ACTIVATION; SUBTYPES; CELLS; INTERNALIZATION; CONFORMATIONS; EXPRESSION
AB G-protein-coupled receptors with dissociable agonists for thyrotropin, parathyroid hormone, and sphingosine-1-phosphate were found to signal persistently hours after agonist withdrawal. Here we show that mouse thyrotropin-releasing hormone (TRH) receptors, subtypes 2 and 1(TRH-R2 and TRH-R1), can signal persistently in HEK-EM293 cells under appropriate conditions, but TRH-R2 exhibits higher persistent signaling activity. Both receptors couple primarily to G alpha(q/11). To gain insight into the mechanism of persistent signaling, we compared proximal steps of inositolmonophosphate (IP1) signaling by TRH-Rs. Persistent signaling was not caused by slower dissociation of TRH from TRH-R2 (t(1/2) = 77 +/- 8.1 min) compared with TRH-R1 (t(1/2) = 82 +/- 12 min) and was independent of internalization, as inhibition of internalization did not affect persistent signaling (115% of control), but required continuously activated receptors, as an inverse agonist decreased persistent signaling by 60%. G alpha(q/11) knockdown decreased persistent signaling by TRH-R2 by 82%, and overexpression of G alpha(q/11) induced persistent signaling in cells expressing TRH-R1. Lastly, persistent signaling was induced in cells expressing high levels of TRH-R1. We suggest that persistent signaling by TRHRs is exhibited when sufficient levels of agonist/receptor/G-protein complexes are established and maintained and that TRH-R2 forms and maintains these complexes more efficiently than TRH-R1.-Boutin, A., Allen, M. D., Neumann, S., Gershengorn, M. C. Persistent signaling by thyrotropin-releasing hormone receptors correlates with G-protein and receptor levels. FASEB J. 26, 3473-3482 (2012). www.fasebj.org
C1 [Boutin, Alisa; Allen, Michael D.; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, LERB, NIH, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, LERB, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
NR 34
TC 6
Z9 6
U1 1
U2 3
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 AUG
PY 2012
VL 26
IS 8
BP 3473
EP 3482
DI 10.1096/fj.12-207860
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 984BI
UT WOS:000307162800034
PM 22593547
ER
PT J
AU Naggie, S
Osinusi, A
Katsounas, A
Lempicki, R
Herrmann, E
Thompson, AJ
Clark, PJ
Patel, K
Muir, AJ
McHutchison, JG
Schlaak, JF
Trippler, M
Shivakumar, B
Masur, H
Polis, MA
Kottilil, S
AF Naggie, Susanna
Osinusi, Anu
Katsounas, Antonios
Lempicki, Richard
Herrmann, Eva
Thompson, Alexander J.
Clark, Paul J.
Patel, Keyur
Muir, Andrew J.
McHutchison, John G.
Schlaak, Joerg F.
Trippler, Martin
Shivakumar, Bhavana
Masur, Henry
Polis, Michael A.
Kottilil, Shyam
TI Dysregulation of innate immunity in hepatitis C virus genotype 1
IL28B-unfavorable genotype patients: Impaired viral kinetics and
therapeutic response
SO HEPATOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENETIC-VARIATION; PEGYLATED INTERFERON;
COINFECTED PATIENTS; INTERLEUKIN 28B; IL28B; EXPRESSION; RIBAVIRIN; HCV;
ASSOCIATION
AB Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. Conclusion: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression. (HEPATOLOGY 2012)
C1 [Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Naggie, Susanna; Thompson, Alexander J.; Clark, Paul J.; Patel, Keyur; Muir, Andrew J.] Duke Clin Res Inst, Durham, NC USA.
[Osinusi, Anu; Katsounas, Antonios; Lempicki, Richard] SAIC Frederick Inc, Frederick, MD USA.
[Herrmann, Eva] Goethe Univ Frankfurt, IBMM, Frankfurt, Germany.
[McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Schlaak, Joerg F.; Trippler, Martin] Univ Hosp Essen, Essen, Germany.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012; Clark, Paul/A-1480-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Clark, Paul/0000-0002-1821-4969;
Polis, Michael/0000-0002-9151-2268; Schlaak, Joerg/0000-0002-9499-1014
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Cancer Institute, National Institutes of
Health [HSN261200800001E]
FX Supported in whole or in part by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National Cancer
Institute, National Institutes of Health, under contract no.
HSN261200800001E.
NR 28
TC 48
Z9 48
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2012
VL 56
IS 2
BP 444
EP 454
DI 10.1002/hep.25647
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 979GF
UT WOS:000306804500007
PM 22331604
ER
PT J
AU Chan, JK
Roth, J
Oppenheim, JJ
Tracey, KJ
Vogl, T
Feldmann, M
Horwood, N
Nanchahal, J
AF Chan, James K.
Roth, Johannes
Oppenheim, Joost J.
Tracey, Kevin J.
Vogl, Thomas
Feldmann, Marc
Horwood, Nicole
Nanchahal, Jagdeep
TI Alarmins: awaiting a clinical response
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MOBILITY GROUP BOX-1; GLYCATION END-PRODUCTS; JUVENILE IDIOPATHIC
ARTHRITIS; MYELOID-RELATED PROTEINS; NF-KAPPA-B; EPITOPE-SPECIFIC
IMMUNOTHERAPY; PROINFLAMMATORY S100 PROTEINS; ISCHEMIA-REPERFUSION
INJURY; CALCIUM-BINDING PROTEINS; MESENCHYMAL STEM-CELLS
AB Alarmins are endogenous molecules that are constitutively available and released upon tissue damage and activate the immune system. Current evidence indicates that uncontrolled and excessive release of alarmins contributes to the dysregulated processes seen in many inflammatory and autoimmune conditions, as well as tumorigenesis and cancer spread. Conversely, alarmins have also been found to play a major role in the orchestration of tissue homeostasis, including repair and remodeling in the heart, skin, and nervous system. Here, we provide an update and overview on alarmins, highlighting the areas that may benefit from this clinical translation.
C1 [Chan, James K.; Feldmann, Marc; Horwood, Nicole; Nanchahal, Jagdeep] Univ Oxford, Kennedy Inst Rheumatol, London W6 8LH, England.
[Roth, Johannes; Vogl, Thomas] Univ Munster, Inst Immunol, Munster, Germany.
[Oppenheim, Joost J.] NCI, Frederick, MD 21701 USA.
[Tracey, Kevin J.] Feinstein Inst Med Res, New York, NY USA.
RP Chan, JK (reprint author), Univ Oxford, Kennedy Inst Rheumatol, 65 Aspenlea Rd, London W6 8LH, England.
EM james.chan@kennedy.ox.ac.uk
OI Nanchahal, Jagdeep/0000-0002-9579-9411; Tracey, Kevin
J/0000-0003-1884-6314
FU Wellcome Trust [096035]; Royal College of Surgeons of England; AO
Foundation [F-09-23N]; Novo Nordisk; Merck; Wyeth; GSK
FX James Chan was supported by the Wellcome Trust [096035] and the Royal
College of Surgeons of England. Project no. F-09-23N was supported by
the AO Foundation.; Marc Feldmann is a shareholder in Merck, Johnson &
Johnson, Maimonidex, Xenexus, and BioAtrix. He is a consultant for
Halozyme TetraLogic Pharmaceuticals and GlaxoSmithKline (GSK) and
receives research support from Novo Nordisk, Merck, Wyeth, and GSK.
NR 149
TC 130
Z9 133
U1 3
U2 15
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2012
VL 122
IS 8
BP 2711
EP 2719
DI 10.1172/JCI62423
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 983OM
UT WOS:000307128600003
PM 22850880
ER
PT J
AU Arias, IM
AF Arias, Irwin M.
TI Liver function from Y to Z
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID BINDING-PROTEIN; RAT-LIVER; FATTY-ACIDS; LIGANDIN; BILIRUBIN; TISSUES;
CYTOSOL; ANIONS
AB In the 1960s, my lab was interested in understanding how bilirubin and other organic anions are transferred from the plasma through the liver cell and into the bile. We performed gel filtration of liver supernatants and identified two protein fractions, designated Y and Z, which bound organic anions including bilirubin, and thus we proposed that they were involved in hepatic uptake of organic anions from plasma. Subsequently, the Y and Z proteins responsible for this binding activity were purified, cloned, and sequenced. Y was identified as a member of the glutathione S-transferase (GST) protein family and Z found to be a member of the fatty acid-binding protein (FABP) family. These proteins have since been shown to have additional surprising roles, but understanding of their full role in physiology and disease has not yet been achieved.
C1 [Arias, Irwin M.] NIH, Bethesda, MD 20892 USA.
RP Arias, IM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, SIPT, 18T Ctr Dr,Room 101,MSC 5430, Bethesda, MD 20892 USA.
EM ariasi@mail.nih.gov
NR 13
TC 4
Z9 6
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2012
VL 122
IS 8
BP 2763
EP 2764
DI 10.1172/JCI64587
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 983OM
UT WOS:000307128600010
PM 23024981
ER
PT J
AU Boonnak, K
Subbarao, K
AF Boonnak, Kobporn
Subbarao, Kanta
TI Memory CD4(+) T cells: beyond "helper" functions
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID INFLUENZA-A VIRUS; LETHAL INFLUENZA; B-CELLS; IMMUNITY; MECHANISMS;
RESPONSES; PERFORIN; PROTECTION; CHALLENGE; INFECTION
AB In influenza virus infection, antibodies, memory CD8(+) T cells, and CD4(+) T cells have all been shown to mediate immune protection, but how they operate and interact with one another to mediate efficient immune responses against virus infection is not well understood. In this issue of the JCI, McKinstry et al. have identified unique functions of memory CD4(+) T cells beyond providing "help" for B cell and CD8(+) T cell responses during influenza virus infection.
C1 [Subbarao, Kanta] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-I,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM KSUBBARAO@niaid.nih.gov
FU Intramural NIH HHS
NR 25
TC 6
Z9 6
U1 0
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2012
VL 122
IS 8
BP 2768
EP 2770
DI 10.1172/JCI65208
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 983OM
UT WOS:000307128600012
PM 22820285
ER
PT J
AU Rachel, RA
May-Simera, HL
Veleri, S
Gotoh, N
Choi, BY
Murga-Zamalloa, C
McIntyre, JC
Marek, J
Lopez, I
Hackett, AN
Zhang, J
Brooks, M
den Hollander, AI
Beales, PL
Li, TS
Jacobson, SG
Sood, R
Martens, JR
Liu, P
Friedman, TB
Khanna, H
Koenekoop, RK
Kelley, MW
Swaroop, A
AF Rachel, Rivka A.
May-Simera, Helen L.
Veleri, Shobi
Gotoh, Norimoto
Choi, Byung Yoon
Murga-Zamalloa, Carlos
McIntyre, Jeremy C.
Marek, Jonah
Lopez, Irma
Hackett, Alice N.
Zhang, Jun
Brooks, Matthew
den Hollander, Anneke I.
Beales, Philip L.
Li, Tiansen
Jacobson, Samuel G.
Sood, Raman
Martens, Jeffrey R.
Liu, Paul
Friedman, Thomas B.
Khanna, Hemant
Koenekoop, Robert K.
Kelley, Matthew W.
Swaroop, Anand
TI Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory
defects and restores ciliogenesis (vol 122, pg 1233, 2012)
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Correction
C1 [Rachel, Rivka A.; Veleri, Shobi; Gotoh, Norimoto; Hackett, Alice N.; Brooks, Matthew; Li, Tiansen; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD USA.
[Choi, Byung Yoon; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Bethesda, MD USA.
[Murga-Zamalloa, Carlos; Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[McIntyre, Jeremy C.; Martens, Jeffrey R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Marek, Jonah; Lopez, Irma; Koenekoop, Robert K.] McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ, Canada.
[Zhang, Jun] NEI, Histopathol Core Facil, NIH, Bethesda, MD 20892 USA.
[den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6525 ED Nijmegen, Netherlands.
[den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Beales, Philip L.] UCL Inst Child Hlth, Mol Med Unit, London, England.
[Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Sood, Raman; Liu, Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Rachel, RA (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RI Liu, Paul/A-7976-2012; Hollander, Anneke/N-4911-2014
OI Liu, Paul/0000-0002-6779-025X;
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2012
VL 122
IS 8
BP 3025
EP 3025
DI 10.1172/JCI65432
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 983OM
UT WOS:000307128600039
ER
PT J
AU Freidlin, RZ
Kakareka, JW
Pohida, TJ
Komlosh, ME
Basser, PJ
AF Freidlin, R. Z.
Kakareka, J. W.
Pohida, T. J.
Komlosh, M. E.
Basser, P. J.
TI A spin echo sequence with a single-sided bipolar diffusion gradient
pulse to obtain snapshot diffusion weighted images in moving media
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Motion artifacts; DWI; DTI; Heart; Spinal cord; Diffusion; MRI
ID MAGNETIC-RESONANCE; IN-VIVO; SELF-DIFFUSION; CARDIAC FIBER; HUMAN BRAIN;
DTI DATA; TENSOR; MR; NMR; MOTION
AB In vivo MRI data can be corrupted by motion. Motion artifacts are particularly troublesome in Diffusion Weighted MRI (DWI), since the MR signal attenuation due to Brownian motion can be much less than the signal loss due to dephasing from other types of complex tissue motion, which can significantly degrade the estimation of self-diffusion coefficients, diffusion tensors, etc. This paper describes a snapshot DWI sequence, which utilizes a novel single-sided bipolar diffusion sensitizing gradient pulse within a spin echo sequence. The proposed method shortens the diffusion time by applying a single refocused bipolar diffusion gradient on one side of a refocusing RF pulse, instead of a set of diffusion sensitizing gradients, separated by a refocusing RF pulse, while reducing the impact of magnetic field inhomogeneity by using a spin echo sequence. A novel MRI phantom that can exhibit a range of complex motions was designed to demonstrate the robustness of the proposed DWI sequence. Published by Elsevier Inc.
C1 [Freidlin, R. Z.; Kakareka, J. W.; Pohida, T. J.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Komlosh, M. E.; Basser, P. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA.
RP Freidlin, RZ (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM raisa@helix.nih.gov
RI Basser, Peter/H-5477-2011;
OI Kakareka, John/0000-0003-0072-0035
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Center for Information Technology, National Institutes of
Health, Bethesda, Maryland
FX R.Z.F thanks Kenneth Kempner and Dr. Benes Trus for their support and
encouragement. The authors thank Drs. Alexandru Avram, Martin Lizak, and
belle Sarlls for helpful discussions and Liz Salak for editing this
paper. We would also like to thank the those who were involved in
providing this research with the pig spinal cord tissue: Mr. R.R.
Clevenger, Mr. T.J. Hunt, Ms. G.J. Zywicke, Mr. A.D. Zetts, Mrs. K.
Keeran, Mr. S.M. Kozlov, and Mr. K.R. Jeffries, from LAMS, NHLBI. This
research was sponsored by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the Center for Information Technology, National Institutes of
Health, Bethesda, Maryland.
NR 43
TC 3
Z9 3
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD AUG
PY 2012
VL 221
BP 24
EP 31
DI 10.1016/j.jmr.2012.04.010
PG 8
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 987JZ
UT WOS:000307414500005
PM 22743539
ER
PT J
AU Potapov, A
Thurber, KR
Yau, WM
Tycko, R
AF Potapov, Alexey
Thurber, Kent R.
Yau, Wai-Ming
Tycko, Robert
TI Dynamic nuclear polarization-enhanced H-1-C-13 double resonance NMR in
static samples below 20 K
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Dynamic nuclear polarization; Double resonance probe; Polarizing agent;
Transverse relaxation
ID SPECTRAL-DIFFUSION DECAY; MAGNETIC-RESONANCE; MEMBRANE-PROTEINS;
2-DIMENSIONAL NMR; AMYLOID FIBRILS; HIGH-RESOLUTION; SPIN ECHOES; DNP
NMR; SPECTROSCOPY; RELAXATION
AB We demonstrate the feasibility of one-dimensional and two-dimensional H-1-C-13 double resonance NMR experiments with dynamic nuclear polarization (DNP) at 9.4T and temperatures below 20 K, including both H-1-C-13 cross-polarization and H-1 decoupling, and discuss the effects of polarizing agent type, polarizing agent concentration, temperature, and solvent deuteration. We describe a two-channel low-temperature DNP/NMR probe, capable of carrying the radio-frequency power load required for H-1-C-13 cross-polarization and high-power proton decoupling. Experiments at 8 K and 16 K reveal a significant T-2 relaxation of C-13, induced by electron spin flips. Carr-Purcell experiments and numerical simulations of Carr-Purcell dephasing curves allow us to determine the effective correlation time of electron flips under our experimental conditions. The dependence of the DNP signal enhancement on electron spin concentration shows a maximum near 80 mM. Although no significant difference in the absolute DNP enhancements for triradical (DOTOPA-TEMPO) and biradical (TOTAPOL) dopants was found, the triradical produced greater DNP build-up rates, which are advantageous for DNP experiments. Additionally the feasibility of structural measurements on C-13-labeled biomolecules was demonstrated with a two-dimensional C-13-C-13 exchange spectrum of selectively C-13-labeled beta-amyloid fibrils. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Potapov, Alexey; Thurber, Kent R.; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Potapov, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM potapovai@niddk.nih.gov
OI Potapov, Alexey/0000-0002-9518-4679
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health; Human Frontier Science Program
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health. AP was supported by a postdoctoral
research fellowship from the Human Frontier Science Program.
NR 63
TC 21
Z9 21
U1 3
U2 31
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD AUG
PY 2012
VL 221
BP 32
EP 40
DI 10.1016/j.jmr.2012.05.008
PG 9
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 987JZ
UT WOS:000307414500006
PM 22743540
ER
PT J
AU Wang, Y
Schwieters, CD
Tjandra, N
AF Wang, Yu
Schwieters, Charles D.
Tjandra, Nico
TI Parameterization of solvent-protein interaction and its use on NMR
protein structure determination
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Protein structure; Structure refinement; Solvent accessibility; Solvent
PRE
ID RESIDUAL DIPOLAR COUPLINGS; ROTATIONAL DIFFUSION; STRUCTURE REFINEMENT;
RELAXATION ENHANCEMENTS; PSEUDOCONTACT SHIFTS; GLOBULAR-PROTEINS;
MOLECULAR SHAPE; COMPLEXES; HYDRATION; WATER
AB NMR structure determination is frequently hindered by an insufficient amount of distance information for determining the correct fold of the protein in its early stages. In response we introduce a simple and general structure-based metric that can be used to incorporate NMR-based restraints on protein surface accessibility. This metric is inversely proportional to the sum of the inverse square distances to neighboring heavy atoms. We demonstrate the use of this restraint using a dataset from the water to protein magnetization transfer experiment on the protein Bax and the solvent paramagnetic relaxation enhancement experiment on the protein ubiquitin and Qua1 homodimer. The calculated solvent accessibility values using the new empirical function are well correlated with the experimental data. By incorporating an associated energy term into Xplor-NIH, we show that structure calculation with a limited number of additional experimental restraints, improves both the precision and accuracy of the resulting structures. This new empirical energy term will have general applicability to other types of solvent accessibility data. Published by Elsevier Inc.
C1 [Wang, Yu; Tjandra, Nico] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA.
[Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
RI wang, yu/A-3473-2011
FU NIH Intramural Research Programs of CIT; NHLBI
FX We are grateful to Motoshi Suzuki for the help on experimental setup and
Yi He for fermentation preparation of isotopically labeled Bax. We thank
Tobias Madl and Michael Sattler for providing us with the solvent PRE
data. This work was supported by the NIH Intramural Research Programs of
CIT (C.D.S) and NHLBI (N.T.).
NR 50
TC 14
Z9 14
U1 2
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD AUG
PY 2012
VL 221
BP 76
EP 84
DI 10.1016/j.jmr.2012.05.020
PG 9
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 987JZ
UT WOS:000307414500011
PM 22750253
ER
PT J
AU Qian, CQ
Masad, IS
Rosenberg, JT
Elumalai, M
Brey, WW
Grant, SC
Gor'kov, PL
AF Qian, Chunqi
Masad, Ihssan S.
Rosenberg, Jens T.
Elumalai, Malathy
Brey, William W.
Grant, Samuel C.
Gor'kov, Peter L.
TI A volume birdcage coil with an adjustable sliding tuner ring for
neuroimaging in high field vertical magnets: Ex and in vivo applications
at 21.1 T
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE High magnetic field; MRI; RF coil design; Birdcage coil; Vertical bore
MRI; Sliding-ring; 900 MHz; 21.1 Tesla; B-1 homogeneity; MRI of rats; In
vivo MRI
ID CAGE RESONATOR; MRI; NMR; SPECTROSCOPY; MICROSCOPY; FREQUENCY; SAMPLES;
DESIGN; BRAIN; TESLA
AB A tunable 900 MHz transmit/receive volume coil was constructed for H-1 MR imaging of biological samples in a 21.1 T vertical bore magnet. To accommodate a diverse range of specimen and RF loads at such a high frequency, a sliding-ring adaptation of a low-pass birdcage was implemented through simultaneous alteration of distributed capacitance. To make efficient use of the constrained space inside the vertical bore, a modular probe design was implemented with a bottom-adjustable tuning and matching apparatus. The sliding ring coil displays good homogeneity and sufficient tuning range for different samples of various dimensions representing large span of RF loads. High resolution in vivo and ex vivo images of large rats (up to 350 g), mice and human postmortem tissues were obtained to demonstrate coil functionality and to provide examples of potential applications at 21.1 T. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Qian, Chunqi] NINDS, NIH, Bethesda, MD 20892 USA.
[Qian, Chunqi; Masad, Ihssan S.; Rosenberg, Jens T.; Elumalai, Malathy; Brey, William W.; Grant, Samuel C.; Gor'kov, Peter L.] Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
[Masad, Ihssan S.; Rosenberg, Jens T.; Grant, Samuel C.] Florida State Univ, Tallahassee, FL 32310 USA.
[Masad, Ihssan S.] King Faisal Univ, Coll Engn, Dept Biomed Engn, Al Hasa 31982, Saudi Arabia.
RP Qian, CQ (reprint author), NINDS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM qianc2@ninds.nih.gov; pgorkov@magnet.fsu.edu
RI Qian, Chunqi/A-7481-2012; Masad, Ihssan/A-8498-2013; Grant,
Samuel/D-8744-2013
OI Grant, Samuel/0000-0001-7738-168X
FU National High Magnetic Field Laboratory [DMR-0654118]; National Science
Foundation; State of Florida; NHMFL; Bruker Biospin Corp.; National
Institutes of Health, NINDS
FX This work was supported by the National High Magnetic Field Laboratory
through Cooperative Agreement (DMR-0654118) with the National Science
Foundation and the State of Florida as well as the NHMFL User
Collaboration Grants Program (to SCG). The authors would like to thank
Richard Desilets for careful machining of all probe parts, Barbara Beck
and Dr. Victor Schepkin for helpful comments and suggestions, as well as
Drs. Dennis Dickson, Zbigniew Wszoleck and Karunya Kanimalla of the Mayo
Clinic for tissue specimens. C.Q. is grateful for financial support from
Bruker Biospin Corp. and the National Institutes of Health, NINDS.
NR 37
TC 9
Z9 9
U1 1
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD AUG
PY 2012
VL 221
BP 110
EP 116
DI 10.1016/j.jmr.2012.05.016
PG 7
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 987JZ
UT WOS:000307414500015
PM 22750638
ER
PT J
AU Nayak, L
Iwamoto, FM
Rudnick, JD
Norden, AD
Lee, EQ
Drappatz, J
Omuro, A
Kaley, TJ
AF Nayak, Lakshmi
Iwamoto, Fabio M.
Rudnick, Jeremy D.
Norden, Andrew D.
Lee, Eudocia Quant
Drappatz, Jan
Omuro, Antonio
Kaley, Thomas J.
TI Atypical and anaplastic meningiomas treated with bevacizumab
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Meningioma; Atypical; Anaplastic; Bevacizumab; Vascular endothelial
growth factor (VEGF)
ID RECURRENT MENINGIOMA; PHASE-II
AB Atypical and anaplastic (WHO Grades II and III) meningiomas are aggressive tumors, and patients often progress despite surgery and radiation. There is no known effective chemotherapeutic option for these patients. Meningiomas have a high expression of vascular endothelial growth factor receptor (VEGFR). We sought to retrospectively study the activity of bevacizumab, which is an anti-angiogenic agent targeting the VEGF pathway in these tumors. This is a retrospective review of WHO Grade II and III meningiomas treated at four institutions, selecting only those patients who received bevacizumab. We analyzed radiographic response according to standard RANO criteria, progression-free survival (PFS) and overall survival from the initiation of bevacizumab therapy using Kaplan-Meier statistics. We identified 15 patients across four institutions who carried a diagnosis of atypical or anaplastic meningioma and were treated with bevacizumab. Best radiographic response was stable disease. MR perfusion studies showed decreased tumor blood volume in one patient. Three patients developed non-fatal intratumoral hemorrhage. Median PFS was 26 weeks (95 % CI, 10-29 weeks). Six month PFS rate was 43.8 % (95 % CI, 15.7-69.1 %). Bevacizumab was well-tolerated in our patients, and may be considered in patients who have exhausted radiation and surgical options. Prospective studies are required to define the safety and efficacy of bevacizumab in atypical and anaplastic meningiomas.
C1 [Nayak, Lakshmi; Omuro, Antonio; Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
[Iwamoto, Fabio M.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Rudnick, Jeremy D.] Cedars Sinai Med Ctr, Dept Neurol & Neurosurg, Los Angeles, CA 90048 USA.
[Norden, Andrew D.; Lee, Eudocia Quant; Drappatz, Jan] Univ Pittsburgh, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
RP Kaley, TJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA.
EM Kaleyt@mskcc.org
OI Kaley, Thomas/0000-0002-2540-8518; Omuro, Antonio/0000-0003-4299-3664
FU NCI NIH HHS [P30 CA008748]
NR 10
TC 51
Z9 51
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD AUG
PY 2012
VL 109
IS 1
BP 187
EP 193
DI 10.1007/s11060-012-0886-4
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 981FU
UT WOS:000306953100023
PM 22544653
ER
PT J
AU Floris, G
Borghero, G
Cannas, A
Di Stefano, F
Costantino, E
Murru, MR
Brunetti, M
Restagno, G
Traynor, BJ
Marrosu, MG
Chio, A
Marrosu, F
AF Floris, Gianluca
Borghero, Giuseppe
Cannas, Antonino
Di Stefano, Francesca
Costantino, Emanuela
Murru, Maria R.
Brunetti, Maura
Restagno, Gabriella
Traynor, Bryan J.
Marrosu, Maria G.
Chio, Adriano
Marrosu, Francesco
TI Frontotemporal dementia with psychosis, parkinsonism, visuo-spatial
dysfunction, upper motor neuron involvement associated to expansion of
C9ORF72: a peculiar phenotype?
SO JOURNAL OF NEUROLOGY
LA English
DT Letter
ID LEWY BODIES; LOCUS
C1 [Floris, Gianluca; Borghero, Giuseppe; Cannas, Antonino; Di Stefano, Francesca; Costantino, Emanuela; Marrosu, Maria G.] Univ Cagliari, Dept Neurol, Azienda Univ Osped Cagliari, I-10126 Cagliari, Italy.
[Murru, Maria R.; Marrosu, Maria G.] Univ Cagliari, Multiple Sclerosis Ctr Lab, I-10126 Cagliari, Italy.
[Brunetti, Maura; Restagno, Gabriella] Azienda Sanit Osped Osped Infantile Regina Marghe, Mol Genet Lab, Turin, Italy.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Traynor, Bryan J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Chio, Adriano] Univ Turin, Dept Neurosci, ALS Ctr, San Giovanni Univ Hosp, Turin, Italy.
[Chio, Adriano] Univ Turin, Neurosci Inst Torino NIT, Turin, Italy.
RP Floris, G (reprint author), Univ Cagliari, Dept Neurol, Azienda Univ Osped Cagliari, Sst 554, I-10126 Cagliari, Italy.
EM lgr.floris@tiscali.it
RI Traynor, Bryan/G-5690-2010;
OI Chio, Adriano/0000-0001-9579-5341; Marrosu, Maria
Giovanna/0000-0003-2334-2081; Di Stefano, Francesca/0000-0001-5921-2778
FU Intramural NIH HHS [ZIA AG000933-06, ZIA AG000934-05]
NR 10
TC 29
Z9 29
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD AUG
PY 2012
VL 259
IS 8
BP 1749
EP 1751
DI 10.1007/s00415-012-6444-3
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 985LH
UT WOS:000307267300034
PM 22323211
ER
PT J
AU Martin, S
Wolters, P
Baldwin, A
Gillespie, A
Dombi, E
Walker, K
Widemann, B
AF Martin, Staci
Wolters, Pamela
Baldwin, Andrea
Gillespie, Andrea
Dombi, Eva
Walker, Katherine
Widemann, Brigitte
TI Social-emotional Functioning of Children and Adolescents With
Neurofibromatosis Type 1 and Plexiform Neurofibromas: Relationships With
Cognitive, Disease, and Environmental Variables
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE chronic illness; psychosocial functioning; social skills and development
ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; ECOLOGICAL MODEL; EVENTS;
PERFORMANCE; MANAGEMENT; DISORDERS; IMPACT; ADHD; NF1
AB Objective This descriptive cross-sectional study aimed to determine how cognitive, disease, and environmental variables relate to social-emotional functioning in youth with NF1 and plexiform neurofibromas. Methods Psychological assessments were administered to 53 children (mean age 12.4 years); parents and teachers completed the Behavior Assessment System for Children-Second Edition (BASC-2). Disease severity was quantified by nurse-practitioner ratings and tumor burden, and parents completed a life events checklist to indicate environmental stressors. Results Notable proportions of children scored in the at-risk/clinically significant ranges on several parent and teacher BASC-2 subscales including Somatization, Attention Problems, Depression, and Withdrawal. Combinations of cognitive, disease, and environmental variables predicted scores on parent BASC-2 Internalizing Problems, Behavior Symptoms Index, and Adaptive Skills composites. Conclusions Cognitive, disease, and environmental variables relate to social-emotional outcomes in children with NF1. These youth may benefit from interventions targeting social skills, cognitive functioning, and adaptive ways of coping with NF1-related pain.
C1 [Martin, Staci; Wolters, Pamela; Baldwin, Andrea; Gillespie, Andrea; Dombi, Eva; Widemann, Brigitte] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Walker, Katherine] NCI Frederick, Clin Res Directorate, CMRP, SAIC Frederick Inc, Frederick, MD USA.
RP Martin, S (reprint author), NCI, Pediat Oncol Branch, 9030 Old Georgetown Rd,107, Bethesda, MD 20892 USA.
EM martins@mail.nih.gov
FU Intramural NIH HHS; PHS HHS [HHSN262200477004C]
NR 51
TC 11
Z9 11
U1 3
U2 25
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
EI 1465-735X
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD AUG
PY 2012
VL 37
IS 7
BP 713
EP 724
DI 10.1093/jpepsy/jsr124
PG 12
WC Psychology, Developmental
SC Psychology
GA 981KC
UT WOS:000306965500002
PM 22353803
ER
PT J
AU Garrett, AS
Reiss, AL
Howe, ME
Kelley, RG
Singh, MK
Adleman, NE
Karchemskiy, A
Chang, KD
AF Garrett, Amy S.
Reiss, Allan L.
Howe, Meghan E.
Kelley, Ryan G.
Singh, Manpreet K.
Adleman, Nancy E.
Karchemskiy, Asya
Chang, Kiki D.
TI Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions
in Pediatric Bipolar Disorder
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE bipolar; fMRI; pediatric; amygdala
ID VOXEL-BASED METAANALYSIS; NEURAL ACTIVATION; EMOTIONAL STIMULI;
RATING-SCALE; CHILDREN; FMRI; MANIA; FACES; DEPRESSION; MEDICATION
AB Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses. Method: A total of 20 euthymic adolescents with familial BD (14 male) and 21 healthy control subjects (13 male) underwent fMRI scanning during presentation of happy, sad, and neutral facial expressions. Whole-brain voxelwise analyses were conducted in SPM5, using a three-way analysis of variance (ANOVA) with factors group (BD and healthy control [HC]), facial expression (happy, sad, and neutral versus scrambled), and phase (early and late, corresponding to the first and second half of each block of faces). Results: There were no significant group differences in task performance, age, gender, or IQ. Significant activation from the main effect of group included greater DLPFC activation in the HC group, and greater amygdala/hippocampal activation in the BD group. The interaction of Group X Phase identified clusters in the superior temporal sulcus/insula and visual cortex, where activation increased from the early to late phase of the block for the BD but not the HC group. Conclusions: These findings are consistent with previous studies that suggest deficient prefrontal cortex regulation of heightened amygdala response to emotional stimuli in pediatric BD. Increasing activation over time in superior temporal and visual cortices suggests difficulty processing or disengaging attention from emotional faces in BD. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(8): 821-831.
C1 [Garrett, Amy S.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA.
[Garrett, Amy S.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Chang, Kiki D.] Stanford Univ, Pediat Bipolar Disorders Program, Stanford, CA 94305 USA.
[Adleman, Nancy E.] NIMH, Bethesda, MD 20892 USA.
RP Garrett, AS (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Ctr Interdisciplinary Brain Sci Res, 401 Quarry Rd, Stanford, CA 94305 USA.
EM agarrett@stanford.edu
FU Brain and Behavior Research Foundation; Klingenstein Third Generation
Foundation; National Institutes of Health (NIH) [MH64460-01, MH01142,
MH19908, MH050047, HD31715]; GlaxoSmithKline
FX This work was supported in port by a Brain and Behavior Research
Foundation Young Investigators Award, a Klingenstein Third Generation
Foundation Fellowships (A.G., K.C.), and National Institutes of Health
(NIH) grants MH64460-01 (K.C.) and MH01142, MH19908, MH050047, and
HD31715 (A.R.).; Dr. Reiss has served on a consultant for Novartis. Dr.
Chang has served on the advisory board for Eli Lilly and Co., has served
as a consultant for Bristol-Myers Squibb and Merck and Co., and has
received research support from GlaxoSmithKline. Drs. Garrett, Singh, and
Adleman, Ms. Howe, Mr. Kelley, and Ms. Karchemskiy report no biomedical
financial interests or potential conflicts of interest.
NR 67
TC 20
Z9 21
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD AUG
PY 2012
VL 51
IS 8
BP 821
EP 831
DI 10.1016/j.jaac.2012.06.005
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 983OJ
UT WOS:000307128300010
PM 22840553
ER
PT J
AU Barry, J
Breen, N
Barrett, M
AF Barry, Janis
Breen, Nancy
Barrett, Michael
TI Significance of Increasing Poverty Levels for Determining Late-Stage
Breast Cancer Diagnosis in 1990 and 2000
SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
LA English
DT Article
DE Breast cancer; Poverty; Physician location; Access to care
ID UNITED-STATES; SOCIOECONOMIC-STATUS; CERVICAL-CANCER; HEALTH;
MAMMOGRAPHY; WOMEN; DISPARITIES; PHYSICIANS; CARE; NEIGHBORHOODS
AB We examine the association between late-stage breast cancer diagnosis and residential poverty in Detroit, Atlanta, and San Francisco in 1990 and 2000. We tested whether residence in census tracts with increasing levels of poverty were associated with increased odds of a late-stage diagnosis in 1990 and 2000 and found that it was. To test this, we linked breast cancer cases from the Surveillance, Epidemiology, and End Results cancer registries with poverty data from the census. Tracts were grouped into low, moderate, and high poverty based on the percentage of households reporting income below the poverty level. While late-stage breast cancer rates and the number of women living in high and moderate-poverty areas declined absolutely between 1990 and 2000, estimates from our combined three-city model showed that odds of a late-stage diagnosis remained stubbornly elevated in increasingly poor areas in both years. Non-Hispanic black women faced higher odds of a late-stage diagnosis relative to non-Hispanic white women in both years. In separate regressions for each city, the odds ratios affirm that combining data across cities may be misleading. In 1990 and 2000, only women living in moderately poor neighborhoods of San Francisco faced elevated odds, while in Detroit women in both moderate- and high-poverty areas faced increased likelihood of late-stage diagnosis. In Atlanta, none of the poverty measures were significant in 1990 or 2000. In our test of physician supply on stage, an increase in the number of neighborhood primary care doctor's offices was associated with decreased odds of a late-stage diagnosis only for Detroit residents and for non-Hispanic whites in the three-city model.
C1 [Barry, Janis] Fordham Univ, New York, NY 10023 USA.
[Breen, Nancy] NCI, Appl Res Program, Rockville, MD USA.
[Barrett, Michael] Informat Management Serv Inc, Silver Spring, MD USA.
RP Barry, J (reprint author), Fordham Univ, New York, NY 10023 USA.
EM barryfigurero@fordham.edu
NR 46
TC 5
Z9 5
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1099-3460
J9 J URBAN HEALTH
JI J. Urban Health
PD AUG
PY 2012
VL 89
IS 4
BP 614
EP 627
DI 10.1007/s11524-011-9660-8
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 986IM
UT WOS:000307335300003
PM 22322332
ER
PT J
AU Gautam, R
Nishimura, Y
Lee, WR
Donau, O
Buckler-White, A
Shingai, M
Sadjadpour, R
Schmidt, SD
LaBranche, CC
Keele, BF
Montefiori, D
Mascola, JR
Martin, MA
AF Gautam, Rajeev
Nishimura, Yoshiaki
Lee, Wendy R.
Donau, Olivia
Buckler-White, Alicia
Shingai, Masashi
Sadjadpour, Reza
Schmidt, Stephen D.
LaBranche, Celia C.
Keele, Brandon F.
Montefiori, David
Mascola, John R.
Martin, Malcolm A.
TI Pathogenicity and Mucosal Transmissibility of the R5-Tropic Simian/Human
Immunodeficiency Virus SHIVAD8 in Rhesus Macaques: Implications for Use
in Vaccine Studies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES;
CORECEPTOR SWITCH; ENVELOPE GENE; INFECTED MACAQUES; IN-VIVO; AIDS;
HIV-1; MONKEYS
AB There is an urgent need to develop new pathogenic R5 simian/human immunodeficiency viruses (SHIVs) for the evaluation of candidate anti-HIV vaccines in nonhuman primates. Here, we characterize swarm SHIVAD8 stocks, prepared from three infected rhesus macaques with documented immunodeficiency at the time of euthanasia, for their capacity to establish durable infections in macaques following inoculation by the intravenous (i.v.) or intrarectal (i.r.) route. All three viral stocks (SHIVAD8-CE8J SHIVAD8-CK15) and SHIVAD8-CL98) exhibited robust replication in vivo and caused marked depletion of CD4(+) T cells affecting both memory and naive CD4+ T lymphocyte subsets following administration by either route. Eleven of 22 macaques inoculated with the new SHIVAD8 stocks were euthanized with clinical symptoms of immunodeficiency and evidence of opportunistic infections (Pneumocystis, Candida, and Mycobacterium). A single but unique founder virus, also present in the SHIVAD8-CE8J cm swarm stock, was transmitted to two animals following a single i.r. inoculation of approximately 3 50% animal infectious doses, which is close to the threshold required to establish infection in all exposed animals. Because the three new SHIVAD8 viruses are mucosally transmissible, exhibited tier 2 sensitivity to anti-HIV-1 neutralizing antibodies, deplete CD4(+) T lymphocytes in vivo, and induce AIDS in macaques, they are eminently suitable as challenge viruses in vaccine experiments.
C1 [Gautam, Rajeev; Nishimura, Yoshiaki; Lee, Wendy R.; Donau, Olivia; Buckler-White, Alicia; Shingai, Masashi; Sadjadpour, Reza; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Schmidt, Stephen D.; Mascola, John R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Keele, Brandon F.] NIH, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA.
[LaBranche, Celia C.; Montefiori, David] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM malm@nih.gov
RI Schmidt, Stephen/B-5398-2012
FU National Institute of Allergy and Infectious Disease, National
Institutes of Health; National Cancer Institute [HHSN266200400088C];
Aine McKnight through the Bill and Melinda Gates Foundation's
Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody Vaccine
Immune Monitoring Consortium [38619]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Disease, National
Institutes of Health. The work was also supported in part with federal
funds from the National Cancer Institute under contract
HHSN266200400088C. Plasma samples for determining the neutralization
phenotype of virus stocks were provided by Aine McKnight through the
Bill and Melinda Gates Foundation's Collaboration for AIDS Vaccine
Discovery/Comprehensive Antibody Vaccine Immune Monitoring Consortium
(grant number 38619).
NR 53
TC 22
Z9 22
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2012
VL 86
IS 16
BP 8516
EP 8526
DI 10.1128/JVI.00544-12
PG 11
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300018
PM 22647691
ER
PT J
AU O'Donnell, CD
Wright, A
Vogel, LN
Wei, CJ
Nabel, GJ
Subbarao, K
AF O'Donnell, Christopher D.
Wright, Amber
Vogel, Leatrice N.
Wei, Chih-Jen
Nabel, Gary J.
Subbarao, Kanta
TI Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic
Distances on Challenge with 2009 Pandemic H1N1 Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SWINE-ORIGIN 2009; ANTIBODY-RESPONSES; IMMUNOGLOBULIN-A;
CROSS-PROTECTION; UNITED-STATES; AGE-GROUPS; INFECTION; MICE; VACCINE;
IMMUNITY
AB Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
C1 [O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice N.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wei, Chih-Jen; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 64
TC 21
Z9 21
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2012
VL 86
IS 16
BP 8625
EP 8633
DI 10.1128/JVI.00147-12
PG 9
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300028
PM 22674976
ER
PT J
AU Smalls-Mantey, A
Doria-Rose, N
Klein, R
Patamawenu, A
Migueles, SA
Ko, SY
Hallahan, CW
Wong, H
Liu, B
You, LJ
Scheid, J
Kappes, JC
Ochsenbauer, C
Nabel, GJ
Mascola, JR
Connors, M
AF Smalls-Mantey, Adjoa
Doria-Rose, Nicole
Klein, Rachel
Patamawenu, Andy
Migueles, Stephen A.
Ko, Sung-Youl
Hallahan, Claire W.
Wong, Hing
Liu, Bai
You, Lijing
Scheid, Johannes
Kappes, John C.
Ochsenbauer, Christina
Nabel, Gary J.
Mascola, John R.
Connors, Mark
TI Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected
CD4(+) T Cells Is Directly Associated with the Magnitude of Surface IgG
Binding
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; FC-GAMMA
RECEPTORS; MEDIATED CYTOTOXICITY; MOLECULAR CLONES; RHESUS MACAQUES;
NEUTRALIZING ANTIBODY; TYPE-1 NEUTRALIZATION; DISEASE PROGRESSION;
PROTECTIVE EFFICACY
AB Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera of 20 HIV-1-positive (HIV-1(+)) patients for ADCC. Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4(+) T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4(+) T cell elimination (ICE) by flow cytometry. We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4(+) T cells. No correlation between ADCC and viral load, CD4(+) T cell count, or neutralization of HIV-1(SF162) or other primary viral isolates was detected. Sera pooled from clade B HIV-1(+) individuals exhibited breadth in killing targets infected with HIV-1 from clades A/E, B, and C. Taken together, these data suggest that the total amount of IgG bound to an HIV-1-infected cell is an important determinant of ADCC and that polyvalent antigen-specific Abs are required for a robust ADCC response. In addition, Abs elicited by a vaccine formulated with immunogens from a single clade may generate a protective ADCC response in vivo against a variety of HIV-1 species. Increased understanding of the parameters that dictate ADCC against HIV-1-infected cells will inform efforts to stimulate ADCC activity and improve its potency in vaccinees.
C1 [Smalls-Mantey, Adjoa; Doria-Rose, Nicole; Klein, Rachel; Patamawenu, Andy; Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Ko, Sung-Youl; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hallahan, Claire W.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Wong, Hing; Liu, Bai; You, Lijing] Altor BioSci, Miramar, FL USA.
[Scheid, Johannes] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA.
[Kappes, John C.; Ochsenbauer, Christina] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Kappes, John C.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases.
NR 54
TC 47
Z9 47
U1 3
U2 7
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 AUG
PY 2012
VL 86
IS 16
BP 8672
EP 8680
DI 10.1128/JVI.00287-12
PG 9
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300033
PM 22674985
ER
PT J
AU Wu, F
Ourmanov, I
Kuwata, T
Goeken, R
Brown, CR
Buckler-White, A
Iyengar, R
Plishka, R
Aoki, ST
Hirsch, VM
AF Wu, Fan
Ourmanov, Ilnour
Kuwata, Takeo
Goeken, Robert
Brown, Charles R.
Buckler-White, Alicia
Iyengar, Ranjini
Plishka, Ronald
Aoki, Scott T.
Hirsch, Vanessa M.
TI Sequential Evolution and Escape from Neutralization of Simian
Immunodeficiency Virus SIVsmE660 Clones in Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1/SIV CHIMERIC VIRUS; LONG-TERM NONPROGRESSORS; ANTIBODY-RESPONSES;
HUMORAL IMMUNITY; TYPE-1 INFECTION; HIV-INFECTION; IN-VIVO; ENVELOPE
GLYCOPROTEIN; DISEASE PROGRESSION; MONOCLONAL-ANTIBODY
AB Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) of many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance for evaluating the role of NAb in vaccine protection. In contrast, SIVsmE660 is an uncloned virus that appears to be more sensitive to neutralizing antibody. To evaluate the role of NAb in this model, we generated full-length neutralization-sensitive molecular clones of SIVsmE660 and evaluated two of these by intravenous inoculation of rhesus macaques. All animals became infected and maintained persistent viremia that was accompanied by a decline in memory CD4(+) T cells in blood and bronchoalveolar lavage fluid. High titers of autologous NAb developed by 4 weeks postinoculation but were not associated with control of viremia, and neutralization escape variants were detected concurrently with the generation of NAb. Neutralization escape was associated with substitutions and insertion/deletion polymorphisms in the V1 and V4 domains of envelope. Analysis of representative variants revealed that escape variants also induced NAbs within a few weeks of their appearance in plasma, in a pattern that is reminiscent of the escape of human immunodeficiency virus type I (HIV-1) isolates in humans. Although early variants maintained a neutralization-sensitive phenotype, viruses obtained later in infection were significantly less sensitive to neutralization than the parental viruses. These results indicate that NAbs exert selective pressure that drives the evolution of the Sly envelope and that this model will be useful for evaluating the role of NAb in vaccine-mediated protection.
C1 [Wu, Fan; Ourmanov, Ilnour; Goeken, Robert; Brown, Charles R.; Buckler-White, Alicia; Iyengar, Ranjini; Plishka, Ronald; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Kuwata, Takeo] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan.
[Aoki, Scott T.] Univ Wisconsin Madison, Dept Biochem, Madison, WI USA.
RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
RI Kuwata, Takeo/F-5809-2013; Kumamoto University, CAIDS/G-8446-2013
FU NIAID, NIH
FX This work was supported by the intramural research program of NIAID,
NIH.
NR 69
TC 14
Z9 14
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2012
VL 86
IS 16
BP 8835
EP 8847
DI 10.1128/JVI.00923-12
PG 13
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300048
PM 22696650
ER
PT J
AU Nelson, MI
Vincent, AL
Kitikoon, P
Holmes, EC
Gramer, MR
AF Nelson, Martha I.
Vincent, Amy L.
Kitikoon, Pravina
Holmes, Edward C.
Gramer, Marie R.
TI Evolution of Novel Reassortant A/H3N2 Influenza Viruses in North
American Swine and Humans, 2009-2011
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PANDEMIC H1N1 2009; A H3N2 VIRUS; UNITED-STATES; 2 CHILDREN; PIGS;
ORIGIN; TRANSMISSION; PERSPECTIVE; ARGENTINA; INFECTION
AB Novel H3N2 influenza viruses (H3N2v) containing seven genome segments from swine lineage triple-reassortant H3N2 viruses and a 2009 pandemic H1N1 (H1N1 pdm09) matrix protein segment (pM) were isolated from 12 humans in the United States between August and December 2011. To understand the evolution of these novel H3N2 viruses in swine and humans, we undertook a phylogenetic analysis of 674 M sequences and 388 HA and NA sequences from influenza viruses isolated from North American swine during 2009-2011, as well as HA, NA, and M sequences from eight H3N2v viruses isolated from humans. We identified 34 swine influenza viruses (termed rH3N2p) with the same combination of H3, N2, and pM segments as the H3N2v viruses isolated from humans. Notably, these rH3N2p viruses were generated in swine via reassortment events between H3N2 viruses and the pM segment approximately 4 to 10 times since 2009. The pM segment has also reassorted with multiple distinct lineages of HI virus, especially H1 delta viruses. Importantly, the N2 segment of all H3N2v viruses isolated from humans is derived from a genetically distinct N2 lineage that has circulated in swine since being acquired by reassortment with seasonal human H3N2 viruses in 2001-2002, rather than from the N2 that is associated with the 1998 H3N2 swine lineage. The identification of this N2 variant may have implications for influenza vaccine design and the potential pandemic threat of H3N2v to human age groups with differing levels of prior exposure and immunity.
C1 [Nelson, Martha I.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Vincent, Amy L.; Kitikoon, Pravina] USDA ARS, Virus & Prion Dis Res Unit, Natl Anim Dis Ctr, Ames, IA USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Gramer, Marie R.] Univ Minnesota, Vet Diagnost Lab, St Paul, MN 55108 USA.
RP Nelson, MI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM nelsonma@mail.nih.gov
OI Holmes, Edward/0000-0001-9596-3552
FU Office of Global Affairs at the Department of Health and Human Services
(DHHS)
FX This research was conducted within the context of the Multinational
Influenza Seasonal Mortality Study (MISMS), an on-going international
collaborative effort to understand influenza epidemiology and evolution,
led by the Fogarty International Center, NIH, with funding from the
Office of Global Affairs at the Department of Health and Human Services
(DHHS).
NR 39
TC 68
Z9 68
U1 2
U2 14
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 AUG
PY 2012
VL 86
IS 16
BP 8872
EP 8878
DI 10.1128/JVI.00259-12
PG 7
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300051
PM 22696653
ER
PT J
AU Akahata, W
Nabel, GJ
AF Akahata, Wataru
Nabel, Gary J.
TI A Specific Domain of the Chikungunya Virus E2 Protein Regulates Particle
Formation in Human Cells: Implications for Alphavirus Vaccine Design
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SEMLIKI-FOREST-VIRUS; SITE-DIRECTED MUTATIONS; CHOLESTEROL DEPENDENCE;
ENVELOPE; FUSION; EXIT; E1; ORGANIZATION; ASSOCIATION; ENTRY
AB Virus-like particles (VLPs) can be generated from Chikungunya virus (CHIKV), but different strains yield variable quantities of particles. Here, we define the genetic basis for these differences and show that amino acid 234 in E2 substantially affects VLP production. This site is located within the acid-sensitive region (ASR) known to initiate a major conformational change in E1/E2. Selected other mutations in the ASR, or changes in pH, also increased VLP yield. These results demonstrate that the ASR of E2 plays an important role in regulating particle generation.
C1 [Akahata, Wataru; 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
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, U.S. National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, U.S. National Institutes of Health.
NR 22
TC 17
Z9 17
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2012
VL 86
IS 16
BP 8879
EP 8883
DI 10.1128/JVI.00370-12
PG 5
WC Virology
SC Virology
GA 984NS
UT WOS:000307198300052
PM 22647698
ER
PT J
AU Wang, XX
Mitra, N
Cruz, P
Deng, LW
Varki, N
Angata, T
Green, ED
Mullikin, J
Hayakawa, T
Varki, A
AF Wang, Xiaoxia
Mitra, Nivedita
Cruz, Pedro
Deng, Liwen
Varki, Nissi
Angata, Takashi
Green, Eric D.
Mullikin, Jim
Hayakawa, Toshiyuki
Varki, Ajit
CA NISC Comparative Sequencing Progra
TI Evolution of Siglec-11 and Siglec-16 Genes in Hominins
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE pseudogene; gene conversion; human evolution; human brain; microglia
ID ALZHEIMERS-DISEASE; IMMUNE-SYSTEM; SIALIC ACIDS; IN-VIVO; MICROGLIA;
BRAIN; CELLS; MACROPHAGES; PROTEIN; MECHANISMS
AB We previously reported a human-specific gene conversion of SIGLEC11 by an adjacent paralogous pseudogene (SIGLEC16P), generating a uniquely human form of the Siglec-11 protein, which is expressed in the human brain. Here, we show that Siglec-11 is expressed exclusively in microglia in all human brains studied-a finding of potential relevance to brain evolution, as microglia modulate neuronal survival, and Siglec-11 recruits SHP-1, a tyrosine phosphatase that modulates microglial biology. Following the recent finding of a functional SIGLEC16 allele in human populations, further analysis of the human SIGLEC11 and SIGLEC16/P sequences revealed an unusual series of gene conversion events between two loci. Two tandem and likely simultaneous gene conversions occurred from SIGLEC16P to SIGLEC11 with a potentially deleterious intervening short segment happening to be excluded. One of the conversion events also changed the 5' untranslated sequence, altering predicted transcription factor binding sites. Both of the gene conversions have been dated to similar to 1-1.2 Ma, after the emergence of the genus Homo, but prior to the emergence of the common ancestor of Denisovans and modern humans about 800,000 years ago, thus suggesting involvement in later stages of hominin brain evolution. In keeping with this, recombinant soluble Siglec-11 binds ligands in the human brain. We also address a second-round more recent gene conversion from SIGLEC11 to SIGLEC16, with the latter showing an allele frequency of similar to 0.1-0.3 in a worldwide population study. Initial pseudogenization of SIGLEC16 was estimated to occur at least 3 Ma, which thus preceded the gene conversion of SIGLEC11 by SIGLEC16P. As gene conversion usually disrupts the converted gene, the fact that ORFs of hSIGLEC11 and hSIGLEC16 have been maintained after an unusual series of very complex gene conversion events suggests that these events may have been subject to hominin-specific selection forces.
C1 [Hayakawa, Toshiyuki] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan.
[Wang, Xiaoxia; Mitra, Nivedita; Varki, Ajit] Univ Calif San Diego, Glycobiol Res & Training Ctr, San Diego, CA 92103 USA.
[Wang, Xiaoxia; Mitra, Nivedita; Varki, Ajit] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Wang, Xiaoxia; Mitra, Nivedita; Varki, Ajit] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA.
[Cruz, Pedro; Green, Eric D.; Mullikin, Jim; NISC Comparative Sequencing Progra] NHGRI, NIH, Bethesda, MD 20892 USA.
[Deng, Liwen; Varki, Nissi] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Angata, Takashi] RIKEN Adv Sci Inst, Syst Glycobiol Res Grp, Wako, Saitama, Japan.
RP Hayakawa, T (reprint author), Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan.
EM thayakawa@pri.kyoto-u.ac.jp; a1varki@ucsd.edu
FU National Institutes of Health [P01HL107150, R01GM32373]; Japan Society
for the Promotion of Science; Ministry of Education, Culture, Sports,
Science and Technology [23570271]; G. Harold and Leila Y. Mathers
Charitable Foundation
FX This research was supported by National Institutes of Health grants
P01HL107150 and R01GM32373 to A.V., a Japan Society for the Promotion of
Science Postdoctoral Fellowship for Research Abroad and the Ministry of
Education, Culture, Sports, Science and Technology grant 23570271 to
T.H., and by the G. Harold and Leila Y. Mathers Charitable Foundation.
All anonymized human frozen and paraffin samples for
immunohistochemistry assays were provided by the National Cancer
Institute's Cooperative Human Tissue Network.
NR 58
TC 15
Z9 15
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD AUG
PY 2012
VL 29
IS 8
BP 2073
EP 2086
DI 10.1093/molbev/mss077
PG 14
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 984EA
UT WOS:000307171300017
PM 22383531
ER
PT J
AU Tao, CL
Xia, CL
Chen, XB
Zhou, ZH
Bi, GQ
AF Tao, Changlu
Xia, Chenglong
Chen, Xiaobing
Zhou, Z. Hong
Bi, Guoqiang
TI Ultrastructural analysis of neuronal synapses using state-of-the-art
nano-imaging techniques
SO NEUROSCIENCE BULLETIN
LA English
DT Review
DE synaptic architecture; nano-imaging; super-resolution imaging; STED
microscopy; STORM; PALM; cryoET
ID TRANSMISSION ELECTRON-MICROSCOPY; CELL-ADHESION MOLECULES; CRYOELECTRON
TOMOGRAPHY; POSTSYNAPTIC DENSITY; FLUORESCENCE MICROSCOPY;
LIGHT-MICROSCOPY; 3-DIMENSIONAL STRUCTURE; BIOLOGICAL SPECIMENS;
DIFFRACTION BARRIER; STIMULATED-EMISSION
AB Neuronal synapses are functional nodes in neural circuits. Their organization and activity define an individual's level of intelligence, emotional state and mental health. Changes in the structure and efficacy of synapses are the biological basis of learning and memory. However, investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution. Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution. Here, we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses, emphasizing super-resolution light microscopy and 3-dimensional electron tomography.
C1 [Tao, Changlu; Xia, Chenglong; Zhou, Z. Hong; Bi, Guoqiang] Univ Sci & Technol China, Ctr Integrat Imaging, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China.
[Tao, Changlu; Xia, Chenglong; Zhou, Z. Hong; Bi, Guoqiang] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China.
[Chen, Xiaobing] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
RP Bi, GQ (reprint author), Univ Sci & Technol China, Ctr Integrat Imaging, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China.
EM gqbi@ustc.edu.cn
RI Bi, Guoqiang/E-5075-2013
OI Bi, Guoqiang/0000-0001-8735-3818
FU National Natural Science Foundation of China [30725017, 30928003]; MOST
[2009CB941300]
FX We thank Peijun Zhang for technical advice on cryoET, Yuntao Liu for
help with figure drawing, and Cheng Xu, Nico Wagner, Xiaowei Zhuang and
Pakming Lau for helpful discussions. This review was partly supported by
grants from the National Natural Science Foundation of China (30725017
and 30928003) and MOST (2009CB941300).
NR 85
TC 1
Z9 4
U1 2
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1673-7067
J9 NEUROSCI BULL
JI Neurosci. Bull.
PD AUG
PY 2012
VL 28
IS 4
SI SI
BP 321
EP 332
DI 10.1007/s12264-012-1249-z
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 986NV
UT WOS:000307349900001
PM 22833032
ER
PT J
AU Nagarkatti-Gude, N
Wang, YJ
Ali, MJ
Honavar, SG
Jager, MJ
Chan, CC
AF Nagarkatti-Gude, Nisha
Wang, Yujuan
Ali, Mohammad Javed
Honavar, Santosh G.
Jager, Martine J.
Chan, Chi-Chao
TI Genetics of Primary Intraocular Tumors
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE Choroidal malignant melanoma; primary intraocular lymphoma; primary
vitreoretinal lymphoma; retinoblastoma; uveal melanoma
ID NON-HODGKIN-LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; B-CELL LYMPHOMA; PRIMARY
VITREORETINAL LYMPHOMA; FAMILIAL UVEAL MELANOMA; OF-THE-LITERATURE; HLA
CLASS-I; RETINOBLASTOMA GENE; GERMLINE MUTATIONS; MALT LYMPHOMA
AB Primary intraocular neoplasms are tumors that originate within the eye. The most common malignant primary intraocular tumor in adults is uveal melanoma and the second is primary intraocular lymphoma or vitreoretinal (intraocular) lymphoma. The most common malignant intraocular tumor in children is retinoblastoma. Genetics plays a vital role in the diagnosis and detection of ocular tumors. In uveal melanoma, monosomy 3 is the most common genetic alteration and somatic mutations of BAP1, a tumor suppressor gene, have been reported in nearly 50% of primary uveal melanomas. The retinoblastoma gene RB1 is the prototype tumor suppressor gene-mutations in RB1 alleles lead to inactivated RB protein and the development of retinoblastoma. Immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement is observed in B-cell or T-cell primary vitreoretinal lymphoma, respectively. Other factors related to the genetics of these three common malignancies in the eye are discussed and reviewed.
C1 [Wang, Yujuan; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Nagarkatti-Gude, Nisha; Jager, Martine J.] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands.
[Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Ali, Mohammad Javed; Honavar, Santosh G.] LV Prasad Eye Inst, Ocular Oncol Serv, Hyderabad, Andhra Pradesh, India.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI wang, yujuan/C-8428-2016
FU Intramural NIH HHS [ZIA EY000222-26]
NR 135
TC 8
Z9 8
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD AUG
PY 2012
VL 20
IS 4
BP 244
EP 254
DI 10.3109/09273948.2012.702843
PG 11
WC Ophthalmology
SC Ophthalmology
GA 979VX
UT WOS:000306851300002
PM 22834783
ER
PT J
AU Larson, TA
Hu, MJ
Janik, JE
Nussenblatt, RB
Morris, JC
Sen, HN
AF Larson, Theresa A.
Hu, Mengjun
Janik, John E.
Nussenblatt, Robert B.
Morris, John C.
Sen, H. Nida
TI Interleukin-2 Receptor Targeted Therapy of Ocular Disease of
HTLV-1-associated Adult T-cell Leukemia
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Letter
DE Adult T-cell leukemia/lymphoma; daclizumab; denileukin diftitox; human
T-cell lymphotropic virus type-1; scleritis
ID DACLIZUMAB
AB Purpose: To report two cases of patients with ocular manifestations of human T-cell lymphotropic virus type-1 (HTLV-1) associated adult T-cell leukemia/lymphoma (ATL) who were successfully treated with interleukin-2 receptor targeted therapies.
Method: Case series.
Results: Two patients with HTLV-1-associated ATL developed symptomatic scleritis. In the first case, conjunctival biopsy showed leukemic infiltration that was confirmed by T-cell receptor polymerase chain reaction (PCR) demonstrating a clonal rearrangement. As treatment for ATL, both cases received interleukin-2 receptor targeted therapy. In one patient, daclizumab, a monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor, was used. The second patient was treated with denileukin diftitox, an immunotoxin fusion protein that targets the IL-2 receptor. Improvement in scleritis was noted in both patients.
Conclusion: Scleritis in patients with underlying HTLV-1-associated ATL is responsive to IL-2 receptor targeted therapies.
C1 [Larson, Theresa A.; Hu, Mengjun; Nussenblatt, Robert B.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Janik, John E.; Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
NR 6
TC 3
Z9 4
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD AUG
PY 2012
VL 20
IS 4
BP 312
EP 314
DI 10.3109/09273948.2012.689071
PG 3
WC Ophthalmology
SC Ophthalmology
GA 979VX
UT WOS:000306851300014
PM 22642512
ER
PT J
AU Gerwick, WH
Hamel, E
White, JD
Gerwick, L
Sherman, DH
Smith, JL
AF Gerwick, W. H.
Hamel, E.
White, J. D.
Gerwick, L.
Sherman, D. H.
Smith, J. L.
TI Integrating disciplines in the natural products sciences: The story of
Curacin A
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Gerwick, W. H.; Gerwick, L.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92037 USA.
[Gerwick, W. H.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92037 USA.
[Hamel, E.] NCI, Screening Technol Branch, Frederick Natl Lab Canc Res, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[White, J. D.] Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA.
[Sherman, D. H.; Smith, J. L.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Sherman, D. H.; Smith, J. L.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 1
U2 10
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1034
EP 1034
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800021
ER
PT J
AU Sorkin, BC
Brown, PN
Hopp, DC
Betz, JM
AF Sorkin, B. C.
Brown, P. N.
Hopp, D. C.
Betz, J. M.
TI Accuracy, precision and reliability in natural product analysis:
mechanisms of NIH support for methods development and validation
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Sorkin, B. C.; Betz, J. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Brown, P. N.] British Columbia Inst Technol, Nat Hlth & Food Prod Res Grp, Ctr Appl Res & Innovat, Burnaby, BC, Canada.
[Hopp, D. C.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1055
EP 1055
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800092
ER
PT J
AU Takebe, Y
Saucedo, CJ
Lund, G
Uenishi, R
Hase, S
Tsuchiura, T
Knetman, N
Ramessar, K
Tyrrell, DLJ
Shirakura, M
Wakita, T
McMahon, JB
O'Keefe, BR
AF Takebe, Y.
Saucedo, C. J.
Lund, G.
Uenishi, R.
Hase, S.
Tsuchiura, T.
Knetman, N.
Ramessar, K.
Tyrrell, D. L. J.
Shirakura, M.
Wakita, T.
McMahon, J. B.
O'Keefe, B. R.
TI Antiviral lectins from red and blue-green algae show potent in vitro and
in vivo activity against Hepatitis C virus
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Takebe, Y.; Uenishi, R.; Hase, S.; Tsuchiura, T.] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 1628640, Japan.
[Saucedo, C. J.] SAIC Frederick, Mol Targets Lab, Frederick, MD 21702 USA.
[Lund, G.; Knetman, N.; Tyrrell, D. L. J.] KMT Hepatech, Edmonton, AB T6G 2E1, Canada.
[Ramessar, K.; McMahon, J. B.; O'Keefe, B. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1060
EP 1060
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800116
ER
PT J
AU Chan, STS
Wilson, JA
Henrich, CJ
Reilly, KM
Gustafson, KR
McMahon, JB
McKee, TC
AF Chan, S. T. S.
Wilson, J. A.
Henrich, C. J.
Reilly, K. M.
Gustafson, K. R.
McMahon, J. B.
McKee, T. C.
TI Isolation and identification of natural products as possible inhibitors
of NF1/TP53-Null astrocytoma cell proliferation
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Chan, S. T. S.; Wilson, J. A.; Gustafson, K. R.; McMahon, J. B.; McKee, T. C.] Frederick Natl Lab Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
[Henrich, C. J.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Reilly, K. M.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1150
EP 1150
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800525
ER
PT J
AU McKEe, TC
Rabe, D
Bokesch, HR
Grkovic, T
Whitson, EL
Diyabalanage, T
Van Wyk, AWW
Marcum, SR
Gardella, RS
Gustafson, KR
Linehan, WM
McMahon, JB
Bottaro, DP
AF McKee, T. C.
Rabe, D.
Bokesch, H. R.
Grkovic, T.
Whitson, E. L.
Diyabalanage, T.
Van Wyk, A. W. W.
Marcum, S. R.
Gardella, R. S.
Gustafson, K. R.
Linehan, W. M.
McMahon, J. B.
Bottaro, D. P.
TI Inhibition of hypoxia inducible Factor-2 transcription: Isolation of
active modulators from marine sponges
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 Ctr Canc Res, Mol Targets Lab, Mol Discovery Program, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
[Rabe, D.; Linehan, W. M.; McMahon, J. B.; Bottaro, D. P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bokesch, H. R.; Gardella, R. S.] SAIC Frederick Inc, Frederick, MD 21702 USA.
RI Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1150
EP 1150
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800526
ER
PT J
AU Li, XC
Baby, KS
Jacob, M
Rao, RR
Agarwal, AK
Newman, DJ
Clark, AM
AF Li, X. C.
Baby, K. S.
Jacob, M.
Rao, R. R.
Agarwal, A. K.
Newman, D. J.
Clark, A. M.
TI Antifungal compounds from four marine sponges
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Li, X. C.; Baby, K. S.; Jacob, M.; Rao, R. R.; Agarwal, A. K.; Clark, A. M.] Univ Mississippi, Inst Pharmaceut Sci, Natl Ctr Nat Prod Res, University, MS 38677 USA.
[Li, X. C.; Clark, A. M.] Univ Mississippi, Dept Pharmacognosy, Sch Pharm, University, MS 38677 USA.
[Newman, D. J.] Natl Canc Inst Frederick, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 1
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1152
EP 1152
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800535
ER
PT J
AU Ruiz, AC
Wilson, JA
Henrich, CJ
Reilly, KM
McMahon, JB
Gustafson, KR
AF Ruiz, Castro A.
Wilson, J. A.
Henrich, C. J.
Reilly, K. M.
McMahon, J. B.
Gustafson, K. R.
TI Antiastrocytoma natural products that target tumor cells with defects in
the tumor suppressor neurofibromin
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Ruiz, Castro A.; Wilson, J. A.; Henrich, C. J.; McMahon, J. B.; Gustafson, K. R.] Frederick Natl Lab Canc Res, Mol Targets Lab, Ft Detrick, MD 21702 USA.
[Henrich, C. J.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Reilly, K. M.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1152
EP 1152
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800534
ER
PT J
AU Zuck, KM
Shipley, S
Giddings, LA
DeLloyd, T
He, M
Newman, DJ
AF Zuck, K. M.
Shipley, S.
Giddings, L. A.
DeLloyd, T.
He, M.
Newman, D. J.
TI Potent spliceostatin analogs isolated from Pseudomonas by mixed
fermentation and modifications of culture conditions
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Zuck, K. M.; Shipley, S.; DeLloyd, T.] SAIC Frederick Inc, Nat Prod Support Grp, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Giddings, L. A.; He, M.; Newman, D. J.] Frederick Natl Lab Canc Res, Nat Prod Branch, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1155
EP 1155
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042800548
ER
PT J
AU Devkota, KP
Covell, D
Ransom, T
McMahon, JB
Beutler, JA
AF Devkota, K. P.
Covell, D.
Ransom, T.
McMahon, J. B.
Beutler, J. A.
TI Growth inhibition of human colon carcinoma cells by diterpenes and
tetralones of Zygogynum calothyrsum
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Devkota, K. P.; Ransom, T.; McMahon, J. B.; Beutler, J. A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Covell, D.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1198
EP 1199
PG 2
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042801181
ER
PT J
AU Polepally, PR
Setola, V
Vardy, E
Roth, BL
Mosier, PD
Zjawiony, JK
AF Polepally, P. R.
Setola, V
Vardy, E.
Roth, B. L.
Mosier, P. D.
Zjawiony, J. K.
TI New salvinorin A - Derived ligands to opioid receptors
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT International Congress on Natural Products Research on Global Change,
Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA,
PSE and SIF
CY JUL 28-AUG 01, 2012
CL New York, NY
SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP)
C1 [Polepally, P. R.; Zjawiony, J. K.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA.
[Polepally, P. R.; Zjawiony, J. K.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA.
[Setola, V; Vardy, E.; Roth, B. L.] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
[Setola, V; Vardy, E.; Roth, B. L.] Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Mosier, P. D.] Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Dept Med Chem, Richmond, VA 23298 USA.
RI Roth, Bryan/F-3928-2010
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2012
VL 78
IS 11
BP 1198
EP 1198
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 982KT
UT WOS:000307042801177
ER
PT J
AU Reddy, UM
Zhang, J
Sun, LP
Chen, Z
Raju, TNK
Laughon, SK
AF Reddy, Uma M.
Zhang, Jun
Sun, Liping
Chen, Zhen
Raju, Tonse N. K.
Laughon, S. Katherine
TI Neonatal mortality by attempted route of delivery in early preterm birth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE early preterm birth; precursors; route of delivery
ID WEIGHT INFANTS BORN; CESAREAN-SECTION; UNITED-STATES; BREECH DELIVERY;
MODE; SURVIVAL
AB OBJECTIVE: We sought to study neonatal outcomes in early preterm births by delivery route.
STUDY DESIGN: Delivery precursors were analyzed in 4352 singleton deliveries, 24 0/7 to 31 6/7 weeks' gestation. In a subset (n = 2906) eligible for a trial of labor, neonatal mortality in attempted vaginal delivery (VD) was compared to planned cesarean delivery stratified by presentation.
RESULTS: Delivery precursors were classified as maternal or fetal conditions (45.7%), preterm premature rupture of membranes (37.7%), and preterm labor (16.6%). For vertex presentation, 79% attempted VD and 84% were successful. There was no difference in neonatal mortality. For breech presentation, at 24 0/7 to 27 6/7 weeks' gestation, 31.7% attempted VD and 27.6% were successful; neonatal mortality was increased (25.2% vs 13.2%, P = .003). At 28 0/7 to 31 6/7 weeks' gestation, 30.5% attempted VD and 17.2% were successful; neonatal mortality was increased (6.0% vs 1.5%, P = .016).
CONCLUSION: Attempted VD for vertex presentation has a high success rate with no difference in neonatal mortality unlike breech presentation.
C1 [Reddy, Uma M.; Zhang, Jun; Sun, Liping; Chen, Zhen; Raju, Tonse N. K.; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Minist Educ, Shanghai, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China.
RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
OI Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX The data included in this article were obtained from the Consortium on
Safe Labor, which was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, through contract no.
HHSN267200603425C.
NR 24
TC 6
Z9 6
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 AUG
PY 2012
VL 207
IS 2
AR 117.e1
DI 10.1016/j.ajog.2012.06.023
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 979WE
UT WOS:000306852200018
PM 22840720
ER
PT J
AU Song, SH
Kim, A
Dale, R
Dean, A
AF Song, Sang-Hyun
Kim, AeRi
Dale, Ryan
Dean, Ann
TI Ldb1 regulates carbonic anhydrase 1 during erythroid differentiation
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE Ldb1; Car1; Car2; Erythroid differentiation
ID MURINE ERYTHROLEUKEMIA-CELLS; GENE-EXPRESSION; POSITIVE ROLE; BINDING;
TRANSCRIPTION; GATA-1; ERYTHROPOIESIS; REQUIREMENT; ACTIVATION;
COMPLEXES
AB Carbonic anhydrase 1 (Car1). an early specific marker of the erythroid differentiation, has been used to distinguish fetal and adult erythroid cells since its production closely follows the gamma- to beta-globin transition, but the molecular mechanism underlying transcriptional regulation of Car1 is unclear. Here, we show that Car1 mRNA decreases significantly when erythroid differentiation is induced in MEL cells. The Ldb1 protein complex including GATA1/SCL/LMO2 binds to the Car1 promoter in uninduced cells and reduced enrichment of the complex during differentiation correlates with loss of Car1 expression. Knockdown of Ldb1 results in a reduction of Ser2 phosphorylated RNA Pol II and Cdk9 at the Car1 promoter region, suggesting that Ldb1 is required for recruitment of Pol II as well as the transcription regulator P-TEFb to enhance elongation of Car1 transcripts. Taken together, these data show that Ldb1 forms a regulatory complex to maintain Car1 expression in erythroid cells. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Song, Sang-Hyun] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea.
[Kim, AeRi] Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, Pusan 609735, South Korea.
[Dale, Ryan; Dean, Ann] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Song, SH (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Room 317,103 Daehak Ro, Seoul 110799, South Korea.
EM song1030@snu.ac.kr
OI Dale, Ryan/0000-0003-2664-3744
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health; Basic Science
Research Program, National Research Foundation of Korea (NRF); Ministry
of Education, Science and Technology [2011-0021123]
FX We thank Dean lab members for helpful discussions. This work was
supported by the Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (A.D.) and the Basic Science Research Program, National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology (2011-0021123) (S.-H.S.).
NR 28
TC 3
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD AUG
PY 2012
VL 1819
IS 8
BP 885
EP 891
DI 10.1016/j.bbagrm.2012.05.001
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 979KG
UT WOS:000306818300006
PM 22609543
ER
PT J
AU Pineda, DM
Rittenhouse, DW
Valley, CC
Cozzitorto, JA
Burkhart, RA
Leiby, B
Winter, JM
Weber, MC
Londin, ER
Rigoutsos, I
Yeo, CJ
Gorospe, M
Witkiewicz, AK
Sachs, JN
Brody, JR
AF Pineda, Danielle M.
Rittenhouse, David W.
Valley, Christopher C.
Cozzitorto, Joseph A.
Burkhart, Richard A.
Leiby, Benjamin
Winter, Jordan M.
Weber, Matthew C.
Londin, Eric R.
Rigoutsos, Isidore
Yeo, Charles J.
Gorospe, Myriam
Witkiewicz, Agnieska K.
Sachs, Jonathan N.
Brody, Jonathan R.
TI HuR's post-transcriptional regulation of death receptor 5 in pancreatic
cancer cells
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE post-transcriptional regulation; DR5; TRAIL; TRAILR2; pancreatic cancer;
pancreatic ductal adenocarcinoma; TRAIL-resistance; apoptosis
ID BINDING PROTEIN HUR; MESSENGER-RNA; APOPTOSIS; GEMCITABINE; LIGAND;
STABILIZATION; TRAIL; TRANSLATION; REGION
AB Apoptosis is one of the core signaling pathways disrupted in pancreatic ductal adenocarcinoma (PDA). Death receptor 5 (DR5) is a member of the tumor necrosis factor (TNF)-receptor superfamily that is expressed in cancer cells. Binding of TNF-related apoptosis-inducing ligand (TRAIL) to DR5 is a potent trigger of the extrinsic apoptotic pathway, and numerous clinical trials are based on DR5-targeted therapies for cancer, including PDA. Human antigen R (HuR), an RNA-binding protein, regulates a select number of transcripts under stress conditions. Here we report that HuR translocates from the nucleus to the cytoplasm of PDA cells upon treatment with a DR5 agonist. High doses of DR5 agonist induce cleavage of both HuR and caspase 8. HuR binds to DR5 mRNA at the 5'-untranslated region (UTR) in PDA cells in response to different cancer-associated stressors and subsequently represses DR5 protein expression; silencing HuR augments DR5 protein production by enabling its translation and thus enhances apoptosis. In PDA specimens (n = 53), negative HuR cytoplasmic expression correlated with elevated DR5 expression (odds ratio 16.1, p < 0.0001). Together, these data demonstrate a feedback mechanism elicited by HuR-mediated repression of the key apoptotic membrane protein DR5.
C1 [Pineda, Danielle M.; Rittenhouse, David W.; Cozzitorto, Joseph A.; Burkhart, Richard A.; Leiby, Benjamin; Winter, Jordan M.; Yeo, Charles J.; Witkiewicz, Agnieska K.; Brody, Jonathan R.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Div Surg Res,Jefferson Pancreas Biliary & Related, Philadelphia, PA 19107 USA.
[Valley, Christopher C.; Sachs, Jonathan N.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN USA.
[Londin, Eric R.; Rigoutsos, Isidore] Thomas Jefferson Univ, Jefferson Med Coll, Computat Med Ctr, Philadelphia, PA 19107 USA.
[Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Weber, Matthew C.; Witkiewicz, Agnieska K.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
RP Brody, JR (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Div Surg Res,Jefferson Pancreas Biliary & Related, Philadelphia, PA 19107 USA.
EM jonathan.brody@jefferson.edu
OI Rigoutsos, Isidore/0000-0003-1529-8631
FU W.W. Smith Charitable Trust; American Cancer Society; ACS-RSG; ACS-IRG
[08-060-01]; Pancreatic Cancer Action Network-AACR; Fund A Cure;
NIA-IRP; NIH
FX J.R.B. and A.K.W. are supported by a W.W. Smith Charitable Trust grant,
a Research Scholar Grant (American Cancer Society, ACS-RSG and ACS-IRG
08-060-01 grants), a Pancreatic Cancer Action Network-AACR grant and
support from "Fund A Cure." M.G. was supported by the NIA-IRP, NIH.
NR 32
TC 19
Z9 19
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD AUG
PY 2012
VL 13
IS 10
BP 946
EP 955
DI 10.4161/cbt.20952
PG 10
WC Oncology
SC Oncology
GA 983KL
UT WOS:000307118100013
PM 22785201
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI A half-century after the molecular clock: new dimensions of molecular
evolution
SO EMBO REPORTS
LA English
DT Editorial Material
ID EVOLVABILITY; MUTATION; PRIONS
AB The EMBO workshop on 'Evolution in the Time of Genomics' took place in May 2012 in the magnificent sixteenth century Palazzo Franchetti near Ponte dell'Accademia in Venice. The meeting focused on phenomena that are not part of the traditional narrative of molecular evolution and which might signal a paradigm shift in the field.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA.
EM koonin@ncbi.nlm.nih.gov
NR 19
TC 1
Z9 1
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD AUG
PY 2012
VL 13
IS 8
BP 664
EP 666
DI 10.1038/embor.2012.103
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 983IP
UT WOS:000307113300003
PM 22791022
ER
PT J
AU Ghosh, AK
Cheng, X
Bai, RL
Hamel, E
AF Ghosh, Arun K.
Cheng, Xu
Bai, Ruoli
Hamel, Ernest
TI Total Synthesis of Potent Antitumor Macrolide (-)-Zampanolide: An
Oxidative Intramolecular Cyclization-Based Strategy
SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
DE Natural products; Total synthesis; C-H activation; Metathesis;
Stereoselective catalysis
ID ENANTIOSELECTIVE TOTAL-SYNTHESIS; MICROTUBULE-STABILIZING AGENT;
CYTOTOXIC MACROLIDE; PRINS CYCLIZATION; (-)-DACTYLOLIDE;
(+)-DACTYLOLIDE; SPONGE; (+)-ZAMPANOLIDE; ZAMPANOLIDE; ACTIVATION
AB A detailed account of the enantioselective total synthesis of ()-zampanolide, a macrolide marine natural product with high anticancer activity, is described. For the synthesis of the 4-methylenetetrahydropyran unit of ()-zampanolide, we initially relied upon an oxidative CH activation of an alkenyl ether and intramolecular cyclization to provide the substituted tetrahydropyran ring. However, this strategy was unsuccessful. Subsequently, we found that a cinnamyl ether is critical for the successful oxidative intramolecular cyclization reaction. The synthesis also features a cross-metathesis reaction for the construction of a trisubstituted olefin, a ring-closing metathesis to form a highly functionalized macrolactone, and a chiral phosphoric acid promoted formation of an N-acyl aminal to furnish ()-zampanolide stereoselectively and in good yield. The synthetic ()-zampanolide had effects on cultured cells and on tubulin assembly consistent with the properties reported for the natural product.
C1 [Ghosh, Arun K.; Cheng, Xu] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Cheng, Xu] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
FU National Institutes of Health; Purdue University
FX Financial support for this work was provided in part by the National
Institutes of Health and Purdue University. The MCF-7, OVCAR-8, and
NCI/ADR-RES human cancer cell lines were generously provided by the
National Cancer Institute drug screening group. Paclitaxel was
generously provided by the Drug Chemistry and Synthesis Branch of the
National Cancer Institute.
NR 40
TC 14
Z9 14
U1 2
U2 46
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1434-193X
J9 EUR J ORG CHEM
JI Eur. J. Org. Chem.
PD AUG
PY 2012
IS 22
BP 4130
EP 4139
DI 10.1002/ejoc.201200286
PG 10
WC Chemistry, Organic
SC Chemistry
GA 981HR
UT WOS:000306958100006
PM 23606808
ER
PT J
AU Inaba, T
Nagamachi, A
Wolff, L
Kolller, R
Honda, H
Matsui, H
AF Inaba, Toshiya
Nagamachi, Akiko
Wolff, Linda
Kolller, Richard
Honda, Hiroaki
Matsui, Hirotaka
TI HAPLOINSUFFICIENCY OF SAMD9LTHAT ENCODES AN ENDOSOME FUSION FACILITATOR
DEVELOPS MYELOID MALIGNANCIES IN MICE MIMICKING HUMAN DISEASES WITH
MONOSOMY 7
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT ISEH 41st Annual Scientific Meeting of the
Society-for-Hematology-and-Stem-Cells
CY AUG 23-26, 2012
CL Amsterdam, NETHERLANDS
SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol
C1 [Inaba, Toshiya; Nagamachi, Akiko; Honda, Hiroaki; Matsui, Hirotaka] Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan.
[Wolff, Linda; Kolller, Richard] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2012
VL 40
IS 8
SU 1
BP S134
EP S134
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 986CY
UT WOS:000307319600208
ER
PT J
AU Thalheimer, F
De Giacomo, P
Korwarsch, A
Theis, F
Hennighausen, L
Schroeder, T
Riegeri, M
AF Thalheimer, Frederic
De Giacomo, Pangrazio
Korwarsch, Andreas
Theis, Fabian
Hennighausen, Lothar
Schroeder, Timm
Riegeri, Michael
TI HEMATOPOIETIC STEM CELL SELF-RENEWAL AND DIFFERENTIATION CONTROL BY
GADD45 GAMMA
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT ISEH 41st Annual Scientific Meeting of the
Society-for-Hematology-and-Stem-Cells
CY AUG 23-26, 2012
CL Amsterdam, NETHERLANDS
SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol
C1 [Thalheimer, Frederic; De Giacomo, Pangrazio; Riegeri, Michael] Inst Biomed Res, Frankfurt, Hesse, Germany.
[Korwarsch, Andreas; Theis, Fabian] Helmholtz Zentrum Munchen, Inst Bioinformat, Neuherberg, Bavaria, Germany.
[Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA.
[Schroeder, Timm] Helmholtz Zentrum Munchen, Inst Stem Cell Res, Neuherberg, Bavaria, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2012
VL 40
IS 8
SU 1
BP S117
EP S117
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 986CY
UT WOS:000307319600183
ER
PT J
AU Hoang, T
Tremblay, M
Tremblay, C
Gerby, B
Herblot, S
Aplan, P
Hebert, J
Perreault, C
AF Trang Hoang
Tremblay, Mathieu
Tremblay, Cedric
Gerby, Bastien
Herblot, Sabine
Aplan, Peter
Hebert, Josee
Perreault, Claude
TI THE SCL, LMO1 AND NOTCH1 ONCOGENES ARE SUFFICIENT TO TRANSFORM THYMOCYTE
PROGENITORS INTO LEUKEMIC STEM CELLS
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT ISEH 41st Annual Scientific Meeting of the
Society-for-Hematology-and-Stem-Cells
CY AUG 23-26, 2012
CL Amsterdam, NETHERLANDS
SP Soc Hematol Stem Cells, Novartis Oncol, Johnson & Johnshon, Jansen Pharmaceut Co, Celgene, Beckman Coulter, Sanquin Blood Supply, MPN Stichting, CellGenix, Life Technol, Miltenyi Biotec, Primorigen Biosci, Inc, STEMCELL Technol
C1 [Trang Hoang; Tremblay, Mathieu; Tremblay, Cedric; Gerby, Bastien; Herblot, Sabine; Hebert, Josee; Perreault, Claude] Univ Montreal, Inst Res Immunol & Canc IRIC, Montreal, PQ, Canada.
[Aplan, Peter] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2012
VL 40
IS 8
SU 1
BP S22
EP S22
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 986CY
UT WOS:000307319600038
ER
PT J
AU Hartog, CS
Skupin, H
Natanson, C
Sun, JF
Reinhart, K
AF Hartog, Christiane S.
Skupin, Helga
Natanson, Charles
Sun, Junfeng
Reinhart, Konrad
TI Systematic analysis of hydroxyethyl starch (HES) reviews: proliferation
of low-quality reviews overwhelms the results of well-performed
meta-analyses
SO INTENSIVE CARE MEDICINE
LA English
DT Review
DE Hydroxyethyl starch; Meta-analysis; pCOI
ID PLASMA-VOLUME EXPANDERS; CRITICALLY-ILL PATIENTS; EVIDENCE-BASED
MEDICINE; SEVERE SEPSIS; 130/0.4 6-PERCENT; RESUSCITATION; THERAPY;
CARE; MANAGEMENT; ALBUMIN
AB Hydroxyethyl starch (HES) is a synthetic colloid used widely for resuscitation despite the availability of safer, less costly fluids. Numerous HES reviews have been published that may have influenced clinicians' practice. We have therefore examined the relationship between the methodological quality of published HES reviews, authors' potential conflicts of interest (pCOI) and the recommendations made.
Systematic analysis of reviews on HES use.
Between 1975 and 2010, 165 reviews were published containing recommendations for or against HES use. From the 1990s onwards, favorable reviews increased from two to eight per year and HES's share of the artificial colloid market tripled from 20 to 60 %. Only 7 % (12/165) of these reviews of HES use contained meta-analyses; these 7 % had higher Overview Quality Assessment Questionnaire (OQAQ) scores [median (range) 6.5 (3-7)] than reviews without meta-analysis [2 (1-4); p < 0.001]. The rates of recommending against HES use are 83 % (10/12) in meta-analyses and 20 % (31/153) in reviews without meta-analysis (p < 0.0001). Fourteen authors published the majority (70/124) of positive reviews, and ten of these 14 had or have since developed a pCOI with various manufacturers of HES.
Low-quality HES reviews reached different conclusions than high-quality meta-analyses from independent entities, such as Cochrane Reviews. The majority of these low-quality positive HES reviews were written by a small group of authors, most of whom had or have since established ties to industry. The proliferation of positive HES reviews has been associated with increased utilization of an expensive therapy despite the lack of evidence for meaningful clinical benefit and increased risks. Clinicians need to be more informed that marketing efforts are potentially influencing scientific literature.
C1 [Hartog, Christiane S.; Skupin, Helga; Reinhart, Konrad] Univ Jena, Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, D-07747 Jena, Germany.
[Natanson, Charles; Sun, Junfeng] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Reinhart, K (reprint author), Univ Jena, Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, Erlanger Allee 101, D-07747 Jena, Germany.
EM konrad.reinhart@med.uni-jena.de
FU Intramural Research Program of the U.S. National Institutes of Health;
official U.S. government
FX The authors thank B. Kabisch, PhD, M. Muecke, and D. Schwarzkopf for
their support in data analysis and J. Maltagliati for editing
assistance. No compensation was received for these contributions. Funds
for this project were provided by the Intramural Research Program of the
U.S. National Institutes of Health. C. Natanson and J. Sun are U.S.
government employees, and both did the work on this paper as part of
their official U.S. government- funded research duties. However, the
opinions expressed do not necessarily represent those of the U.S.
National Institutes of Health.
NR 92
TC 24
Z9 25
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD AUG
PY 2012
VL 38
IS 8
BP 1258
EP 1271
DI 10.1007/s00134-012-2614-0
PG 14
WC Critical Care Medicine
SC General & Internal Medicine
GA 976GY
UT WOS:000306570100004
PM 22790311
ER
PT J
AU Giedd, JN
AF Giedd, Jay N.
TI The Digital Revolution and Adolescent Brain Evolution
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Editorial Material
DE Digital technology; Neurodevelopment; Adolescent; Computer; Internet;
Social networking sites
ID NEURITE OUTGROWTH; VIDEO GAMES; INHIBITOR; MEMORY; IDENTIFICATION;
GLYCOPROTEIN; DISTRACTION; DRIVER; PLEA
AB Remarkable advances in technologies that enable the distribution and use of information encoded as digital sequences of 1s or 0s have dramatically changed our way of life. Adolescents, old enough to master the technologies and young enough to welcome their novelty, are at the forefront of this "digital revolution." Underlying the adolescent's eager embracement of these sweeping changes is a neurobiology forged by the fires of evolution to be extremely adept at adaptation. The consequences of the brain's adaptation to the demands and opportunities of the digital age have enormous implications for adolescent health professionals. (C) 2012 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 NIMH, Brain Imaging Sect, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Giedd, JN (reprint author), NIMH, Brain Imaging Sect, Child Psychiat Branch, Bethesda, MD 20892 USA.
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
FU Intramural NIH HHS [Z99 MH999999]
NR 39
TC 35
Z9 36
U1 3
U2 34
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 AUG
PY 2012
VL 51
IS 2
BP 101
EP 105
DI 10.1016/j.jadohealth.2012.06.002
PG 5
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 977LS
UT WOS:000306663300001
PM 22824439
ER
PT J
AU Jemal, A
Ma, JM
Rosenberg, PS
Siegel, R
Anderson, WF
AF Jemal, Ahmedin
Ma, Jiemin
Rosenberg, Philip S.
Siegel, Rebecca
Anderson, William F.
TI Increasing Lung Cancer Death Rates Among Young Women in Southern and
Midwestern States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CURRENT POPULATION SURVEY; TOBACCO CONTROL PROGRAM; UNITED-STATES;
CIGARETTE-SMOKING; ADULT SMOKERS; TRENDS; MORTALITY; CESSATION; COHORT;
PATTERNS
AB Purpose
Previous studies reported that declines in age-specific lung cancer death rates among women in the United States abruptly slowed in women younger than age 50 years (ie, women born after the 1950s). However, in view of substantial geographic differences in antitobacco measures and sociodemographic factors that affect smoking prevalence, it is unknown whether this change in the trend was similar across all states.
Methods
We examined female age-specific lung cancer death rates (1973 through 2007) by year of death and birth in each state by using age-period-cohort models. Cohort relative risks adjusted for age and period effects were used to compare the lung cancer death rate for a given birth cohort to a referent birth cohort (ie, the 1933 cohort herein).
Results
Age-specific lung cancer death rates declined continuously in white women in California, but the rates declined less quickly or even increased in the remaining states among women younger than age 50 years and women born after the 1950s, especially in several southern and midwestern states. For example, in some southern states (eg, Alabama), lung cancer death rates among women born in the 1960s were approximately double those of women born in the 1930s.
Conclusion
The unfavorable lung cancer trend in white women born after circa 1950 in southern and midwestern states underscores the need for additional interventions to promote smoking cessation in these high-risk populations, which could lead to more favorable future mortality trends for lung cancer and other smoking-related diseases.
C1 [Jemal, Ahmedin; Ma, Jiemin; Siegel, Rebecca] Amer Canc Soc, Surveillance Res Program, Atlanta, GA 30303 USA.
[Rosenberg, Philip S.; Anderson, William F.] NCI, Rockville, MD USA.
RP Jemal, A (reprint author), Amer Canc Soc, Surveillance Res Program, 250 Williams St, Atlanta, GA 30303 USA.
EM ahmedin.jemal@cancer.org
FU Intramural Research Department of the American Cancer Society;
Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX Supported by the Intramural Research Department of the American Cancer
Society and by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute.
NR 43
TC 23
Z9 23
U1 1
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 1
PY 2012
VL 30
IS 22
BP 2739
EP 2744
DI 10.1200/JCO.2012.42.6098
PG 6
WC Oncology
SC Oncology
GA 981FK
UT WOS:000306952100011
PM 22734032
ER
PT J
AU Ksendzovsky, A
Walbridge, S
Saunders, RC
Asthagiri, AR
Heiss, JD
Lonser, RR
AF Ksendzovsky, Alexander
Walbridge, Stuart
Saunders, Richard C.
Asthagiri, Ashok R.
Heiss, John D.
Lonser, Russell R.
TI Convection-enhanced delivery Response
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
ID VIRUS-SIZED PARTICLES; PRIMATE BRAIN
C1 [Ksendzovsky, Alexander; Walbridge, Stuart; Asthagiri, Ashok R.; Heiss, John D.; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bethesda, MD USA.
[Saunders, Richard C.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Ksendzovsky, A (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bethesda, MD USA.
NR 12
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD AUG
PY 2012
VL 117
IS 2
BP 195
EP 196
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 978ST
UT WOS:000306766800002
ER
PT J
AU Ksendzovsky, A
Walbridge, S
Saunders, RC
Asthagiri, AR
Heiss, JD
Lonser, RR
AF Ksendzovsky, Alexander
Walbridge, Stuart
Saunders, Richard C.
Asthagiri, Ashok R.
Heiss, John D.
Lonser, Russell R.
TI Convection-enhanced delivery of M13 bacteriophage to the brain
Laboratory investigation
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE bacteriophage; brain; convection-enhanced delivery; white matter; gray
matter; oncology; Macaca mulatta
ID VIRUS-SIZED PARTICLES; PRIMATE BRAIN; LIPOSOMES; VECTOR; ENDOCYTOSIS;
NEURONS; TRACER
AB Object. Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to beta-amyloid and alpha-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage.
Methods. Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution.
Results. Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 +/- 0.2 in gray matter and 1.9 +/- 0.3 in white matter. The mean values are expressed +/- SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 +/- 0.2 in gray matter and 2.1 +/- 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was -2.2% +/- 9.9% in thalamic gray matter and 9.1% +/- 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 +/- 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity.
Conclusions. The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white matter spread after infusion cessation enhances distribution of this large nanoparticle. Real-time MRI studies of coinfused Gd-DTPA (1 mM) can be used for accurate tracking of distribution during infusion of M13 bacteriophage. (http://thejns.org/doi/abs/10.3171/2012.4.JNS111528)
C1 [Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Saunders, Richard C.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the NIH
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the NIH. This
research was performed under a Materials Transfer Agreement with
NeuroPhage Pharmaceuticals, Inc., Cambridge, Massachusetts. Dr. Lonser
holds a patent with the NIH. The authors report no conflict of interest
concerning the materials or methods used in this study or the findings
specified in this paper.
NR 27
TC 15
Z9 15
U1 0
U2 4
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD AUG
PY 2012
VL 117
IS 2
BP 197
EP 203
DI 10.3171/2012.4.JNS111528
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 978ST
UT WOS:000306766800003
PM 22606981
ER
PT J
AU Engmann, C
Garces, A
Jehan, I
Ditekemena, J
Phiri, M
Mazariegos, M
Chomba, E
Pasha, O
Tshefu, A
McClure, EM
Thorsten, V
Chakraborty, H
Goldenberg, RL
Bose, C
Carlo, WA
Wright, LL
AF Engmann, C.
Garces, A.
Jehan, I.
Ditekemena, J.
Phiri, M.
Mazariegos, M.
Chomba, E.
Pasha, O.
Tshefu, A.
McClure, E. M.
Thorsten, V.
Chakraborty, H.
Goldenberg, R. L.
Bose, C.
Carlo, W. A.
Wright, L. L.
TI Causes of community stillbirths and early neonatal deaths in low-income
countries using verbal autopsy: an International, Multicenter Study
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE early neonatal death; stillbirth; perinatal death; cause of death;
verbal autopsy
ID MORTALITY; BURDEN; CHALLENGES; TANZANIA; DISEASE; RATES; INDIA; GHANA
AB Objective: Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries.
Study Design: This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD).
Result: There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%).
Conclusion: Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life. Journal of Perinatology (2012) 32, 585-592; doi: 10.1038/jp.2011.154; published online 10 November 2011
C1 [Engmann, C.; Bose, C.] Univ N Carolina, Sch Med, Dept Pediat & Maternal Child Hlth, Div Neonatal Perinatal Med, Chapel Hill, NC 27599 USA.
[Engmann, C.; Bose, C.] Univ N Carolina, Sch Publ Hlth, Dept Pediat & Maternal Child Hlth, Div Neonatal Perinatal Med, Chapel Hill, NC 27599 USA.
[Garces, A.] IMSALUD San Carlos Univ, Guatemala City, Guatemala.
[Jehan, I.; Pasha, O.] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Ditekemena, J.; Tshefu, A.] Kinshasa Sch Publ Hlth, Fac Med, Kinshasa, Zaire.
[Phiri, M.; Chomba, E.] Univ Teaching Hosp, Dept Pediat & Child Hlth, Lusaka, Zambia.
[Mazariegos, M.] INCAP, Guatemala City, Guatemala.
[McClure, E. M.; Thorsten, V.; Chakraborty, H.] Res Triangle Inst, Durham, NC USA.
[Goldenberg, R. L.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Carlo, W. A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Wright, L. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Engmann, C (reprint author), Univ N Carolina, Sch Med, Dept Pediat & Maternal Child Hlth, Div Neonatal Perinatal Med,UNC Hosp, CB 7596,4th Floor, Chapel Hill, NC 27599 USA.
EM cengmann@med.unc.edu
FU National Institutes of Child Health and Human Development [U01 HD043475,
U01 HD040636, U01 HD043464, U01 HD040607, U01 HD040657, U01
HD043475-03S1]
FX Funding was provided by grants from the National Institutes of Child
Health and Human Development (U01 HD043475, U01 HD040636, U01 HD043464,
U01 HD040607, U01 HD040657 and U01 HD043475-03S1).
NR 36
TC 10
Z9 10
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD AUG
PY 2012
VL 32
IS 8
BP 585
EP 592
DI 10.1038/jp.2011.154
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 982BB
UT WOS:000307015600005
PM 22076413
ER
PT J
AU Molnar, T
Barabas, P
Birnbaumer, L
Punzo, C
Kefalov, V
Krizaj, D
AF Molnar, Tuende
Barabas, Peter
Birnbaumer, Lutz
Punzo, Claudio
Kefalov, Vladimir
Krizaj, David
TI Store-operated channels regulate intracellular calcium in mammalian rods
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID PLASMA-MEMBRANE; TRPC CHANNELS; CA2+ ENTRY; PHOTORECEPTOR DEGENERATION;
VERTEBRATE PHOTORECEPTORS; SYNAPTIC-TRANSMISSION; RETINAL DEGENERATION;
SKELETAL-MUSCLE; GENE-EXPRESSION; TRANSGENIC MICE
AB Exposure to daylight closes cyclic nucleotide-gated (CNG) and voltage-operated Ca2+-permeable channels in mammalian rods. The consequent lowering of the cytosolic calcium concentration ([Ca2+]i), if protracted, can contribute to light-induced damage and apoptosis in these cells. We here report that mouse rods are protected against prolonged lowering of [Ca2+]i by store-operated Ca2+ entry (SOCE). Ca2+ stores were depleted in Ca2+-free saline supplemented with the endoplasmic reticulum (ER) sequestration blocker cyclopiazonic acid. Store depletion elicited [Ca2+]i signals that exceeded baseline [Ca2+]i by 5.9 +/- 0.7-fold and were antagonized by an inhibitory cocktail containing 2-APB, SKF 96365 and Gd3+. Cation influx through SOCE channels was sufficient to elicit a secondary activation of L-type voltage-operated Ca2+ entry. We also found that TRPC1, the type 1 canonical mammalian homologue of the Drosophila photoreceptor TRP channel, is predominantly expressed within the outer nuclear layer of the retina. Rod loss in Pde6brd1 (rd1), Chx10/Kip(1-/-rd1) and Elovl4TG2 dystrophic models was associated with 70% reduction in Trpc1 mRNA content whereas Trpc1 mRNA levels in rodless cone-full Nrl-/- retinas were decreased by 50%. Genetic ablation of TRPC1 channels, however, had no effect on SOCE, the sensitivity of the rod phototransduction cascade or synaptic transmission at rod and cone synapses. Thus, we localized two new mechanisms, SOCE and TRPC1, to mammalian rods and characterized the contribution of SOCE to Ca2+ homeostasis. By preventing the cytosolic [Ca2+]i from dropping too low under sustained saturating light conditions, these signalling pathways may protect Ca2+-dependent mechanisms within the ER and the cytosol without affecting normal rod function.
C1 [Krizaj, David] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
[Molnar, Tuende; Barabas, Peter; Krizaj, David] Univ Utah, Sch Med, Moran Eye Inst, Salt Lake City, UT 84132 USA.
[Krizaj, David] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84132 USA.
[Birnbaumer, Lutz] NIEHS, NIH, Durham, NC 27709 USA.
[Punzo, Claudio] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA 01605 USA.
[Kefalov, Vladimir] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
RP Krizaj, D (reprint author), Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA.
EM david.krizaj@hsc.utah.edu
OI Krizaj, David/0000-0003-4468-3029
FU National Institutes of Health [RO1 EY13870, P30 EY014800, RO1EY19312,
RO1EY2112601, P30 EY02687]; NIH [Z01-ES101684]; International Retina
Research Foundation; Knights Templar Eye Foundation; Foundation Fighting
Blindness; Department of Defense; University of Utah; Research to
Prevent Blindness
FX The work was supported by the National Institutes of Health (RO1
EY13870; P30 EY014800 to D. K.; RO1EY19312, RO1EY2112601 and P30 EY02687
to V. K.), the Intramural Research Program of the NIH (Z01-ES101684 to
L. B.), The International Retina Research Foundation (P. B.), Knights
Templar Eye Foundation (T. M.), Foundation Fighting Blindness (D. K.),
the Department of Defense (D. K.) University of Utah (D. K.) and by an
unrestricted grant from Research to Prevent Blindness to the Moran Eye
Center at the University of Utah. We thank Mr Wei Xing for technical
support, Mr Christopher Wood for help with viability assays, Dr William
Hauswirth (University of Florida) for the AAV5-mOPS construct and Drs
Edward Levine and Kang Zhang (University of Utah), and Anand Swaroop
(NEI) for generous gifts of Chx10/ Kip1-/-, Nrl: GFP, Nrl-/and Elovl4TG2
mice.
NR 80
TC 18
Z9 18
U1 1
U2 8
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 AUG
PY 2012
VL 590
IS 15
BP 3465
EP 3481
DI 10.1113/jphysiol.2012.234641
PG 17
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 980LD
UT WOS:000306893800014
PM 22674725
ER
PT J
AU Wang, J
Lannotti, RJ
Luk, JW
AF Wang, Jing
Lannotti, Ronald J.
Luk, Jeremy W.
TI Patterns of adolescent bullying behaviors: Physical, verbal, exclusion,
rumor, and cyber
SO JOURNAL OF SCHOOL PSYCHOLOGY
LA English
DT Article
DE Bullying; Cyber bullying; Demographic differences; Externalizing
problems; Latent class analysis
ID PSYCHOSOCIAL ADJUSTMENT; INDIRECT AGGRESSION; VICTIMIZATION; PREVALENCE;
GENDER; YOUTH; QUESTIONNAIRE; ASSOCIATION; INVOLVEMENT; CONSISTENCY
AB Patterns of engagement in cyber bullying and four types of traditional bullying were examined using latent class analysis (LCA). Demographic differences and externalizing problems were evaluated across latent class membership. Data were obtained from the 2005-2006 Health Behavior in School-aged Survey and the analytic sample included 7,508 U.S. adolescents in grades 6 through 10. LCA models were tested on physical bullying, verbal bullying, social exclusion, spreading rumors, and cyber bullying behaviors. Three latent classes were identified for each gender: All-Types Bullies (10.5% for boys and 4.0% for girls), Verbal/Social Bullies (29.3% for boys and 29.4% for girls), and a Non-Involved class (60.2% for boys and 66.6% for girls). Boys were more likely to be All-Types Bullies than girls. The prevalence rates of All-Types and Verbal/Social Bullies peaked during grades 6 to 8 and grades 7 and 8, respectively. Pairwise comparisons across the three latent classes on externalizing problems were conducted. Overall, the All-Types Bullies were at highest risk of using substances and carrying weapons, the Non-Involved were at lowest risk, and the Verbal/Social Bullies were in the middle. Results also suggest that most cyber bullies belong to a group of highly aggressive adolescents who conduct all types of bullying. This finding does not only improve our understanding of the relation between cyber bullying and traditional bullying, but it also suggests that prevention and intervention efforts could target cyber bullies as a high-risk group for elevated externalizing problems. (c) 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.
C1 [Wang, Jing] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Glotech Inc, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Wang, Jing; Lannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Luk, Jeremy W.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
RP Wang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Glotech Inc, Div Epidemiol Stat & Prevent Res, 6100 Bldg Room 7B13 MSC 7510, Bethesda, MD 20892 USA.
EM wangji2@mail.nillgov
FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [N01-HD-5-3401]
NR 51
TC 46
Z9 47
U1 7
U2 72
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-4405
J9 J SCHOOL PSYCHOL
JI J. Sch. Psychol.
PD AUG
PY 2012
VL 50
IS 4
BP 521
EP 534
DI 10.1016/j.jsp.2012.03.004
PG 14
WC Psychology, Educational
SC Psychology
GA 976YG
UT WOS:000306622700006
PM 22710019
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
[Gipson, Chester] AC, USDA, APHIS, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD AUG
PY 2012
VL 41
IS 8
BP 220
EP 220
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 982GN
UT WOS:000307031100015
PM 22821042
ER
PT J
AU Barrett, JA
AF Barrett, John A.
TI T-Cell Therapy for Viral Infections Following Transplantation: Why Stop
at Three Viruses?
SO MOLECULAR THERAPY
LA English
DT Editorial Material
ID ADOPTIVE TRANSFER; CORD BLOOD; RECIPIENTS; EBV; ADENOVIRUS;
CYTOMEGALOVIRUS; LYMPHOCYTES; IMMUNITY; DISEASES
C1 NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Barrett, JA (reprint author), NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM barrettj@nhlbi.nih.gov
NR 17
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD AUG
PY 2012
VL 20
IS 8
BP 1487
EP 1488
DI 10.1038/mt.2012.138
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 983EX
UT WOS:000307102500003
PM 22850720
ER
PT J
AU Lindhurst, MJ
Parker, VER
Payne, F
Sapp, JC
Rudge, S
Harris, J
Witkowski, AM
Zhang, QF
Groeneveld, MP
Scott, CE
Daly, A
Huson, SM
Tosi, LL
Cunningham, ML
Darling, TN
Geer, J
Gucev, Z
Sutton, VR
Tziotzios, C
Dixon, AK
Helliwell, T
O'Rahilly, S
Savage, DB
Wakelam, MJO
Barroso, I
Biesecker, LG
Semple, RK
AF Lindhurst, Marjorie J.
Parker, Victoria E. R.
Payne, Felicity
Sapp, Julie C.
Rudge, Simon
Harris, Julie
Witkowski, Alison M.
Zhang, Qifeng
Groeneveld, Matthijs P.
Scott, Carol E.
Daly, Allan
Huson, Susan M.
Tosi, Laura L.
Cunningham, Michael L.
Darling, Thomas N.
Geer, Joseph
Gucev, Zoran
Sutton, V. Reid
Tziotzios, Christos
Dixon, Adrian K.
Helliwell, Timothy
O'Rahilly, Stephen
Savage, David B.
Wakelam, Michael J. O.
Barroso, Ines
Biesecker, Leslie G.
Semple, Robert K.
TI Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic
activating mutations in PIK3CA
SO NATURE GENETICS
LA English
DT Article
ID PROTEUS-SYNDROME; DIAGNOSTIC-CRITERIA; AKT1; PI3K; CANCERS; H1047R;
DOMAIN; TUMORS; CELLS; MICE
AB The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110 alpha catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in ten additional individuals with overlapping syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases. Affected dermal fibroblasts showed enhanced basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3,4,5-trisphosphate(PIP3) generation and concomitant activation of downstream signaling relative to their unaffected counterparts. Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target.
C1 [Lindhurst, Marjorie J.; Sapp, Julie C.; Witkowski, Alison M.; Biesecker, Leslie G.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Parker, Victoria E. R.; Harris, Julie; Groeneveld, Matthijs P.; O'Rahilly, Stephen; Savage, David B.; Barroso, Ines; Semple, Robert K.] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Cambridge, England.
[Payne, Felicity; Scott, Carol E.; Daly, Allan; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England.
[Rudge, Simon; Zhang, Qifeng; Wakelam, Michael J. O.] Babraham Inst, Cambridge, England.
[Huson, Susan M.] Manchester Acad Hlth Sci Ctr, Genet Unit, Manchester, Lancs, England.
[Tosi, Laura L.] Childrens Natl Med Ctr, Div Orthopaed, Washington, DC 20010 USA.
[Cunningham, Michael L.] Univ Washington, Sch Med, Div Craniofacial Med, Seattle, WA USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD USA.
[Geer, Joseph] Greenwood Genet Ctr, Greenwood, SC 29646 USA.
[Gucev, Zoran] Skopje Med Fac, Dept Endocrinol & Genet, Skopje, Macedonia.
[Sutton, V. Reid] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Tziotzios, Christos] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Dixon, Adrian K.] Univ Cambridge, Sch Clin Med, Cambridge, England.
[Helliwell, Timothy] Univ Liverpool, Liverpool Canc Res UK Ctr, Liverpool L69 3BX, Merseyside, England.
[O'Rahilly, Stephen; Savage, David B.; Semple, Robert K.] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England.
RP Biesecker, LG (reprint author), NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM ib1@sanger.ac.uk; leslieb@helix.nih.gov; rks16@cam.ac.uk
OI Helliwell, Timothy/0000-0003-2112-4128; Semple,
Robert/0000-0001-6539-3069; Darling, Thomas/0000-0002-5161-1974; Payne,
Felicity/0000-0003-4228-581X
FU Proteus Syndrome Foundations of the United States and United Kingdom;
Wellcome Trust [097721/Z/11/Z, 80952/Z/06/Z, 078986/Z/06/Z,
098051/Z/05/Z, 091551/Z/10/Z]; UK Medical Research Council Centre for
Obesity and Related Disorders; UK National Institute for Health Research
(NIHR) Cambridge Biomedical Research Centre; Intramural Research Program
of the National Human Genome Research Institute; Biotechnology and
Biological Sciences Research Council (BBSRC); Manchester NIHR Biomedical
Research Centre
FX The authors thank L. Ivey, J.J. Johnston, V. Tasic, M. Walters and E.
Choolun for support and advice. The authors are especially grateful to
the subjects who participated in this research study and to the Proteus
Syndrome Foundations of the United States and United Kingdom, who have
supported and encouraged these individuals and our research efforts.
V.E.R.P., S.O., D.B.S., I.B. and R.K.S. were supported by the Wellcome
Trust (grants 097721/Z/11/Z, 80952/Z/06/Z, 078986/Z/06/Z, 098051/Z/05/Z
and 091551/Z/10/Z), the UK Medical Research Council Centre for Obesity
and Related Disorders and the UK National Institute for Health Research
(NIHR) Cambridge Biomedical Research Centre. L.G.B., M.J.L., J.C.S. and
A.M.W. were supported by the Intramural Research Program of the National
Human Genome Research Institute. S.R., Q.Z. and M.J.O.W. were supported
by the Biotechnology and Biological Sciences Research Council (BBSRC).
We are grateful for access to exome sequence data from the CoLaus
cohort, which was sequenced as part of a partnership between the
Wellcome Trust Sanger Institute, the CoLaus principal investigators and
the Quantitative Sciences department of GlaxoSmithKline. S.M.H. is
supported by the Manchester NIHR Biomedical Research Centre.
NR 34
TC 93
Z9 94
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2012
VL 44
IS 8
BP 928
EP +
DI 10.1038/ng.2332
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 979WV
UT WOS:000306854700020
PM 22729222
ER
PT J
AU Fawzi, NL
Ying, JF
Torchia, DA
Clore, GM
AF Fawzi, Nicolas L.
Ying, Jinfa
Torchia, Dennis A.
Clore, G. Marius
TI Probing exchange kinetics and atomic resolution dynamics in
high-molecular-weight complexes using dark-state exchange saturation
transfer NMR spectroscopy
SO NATURE PROTOCOLS
LA English
DT Article
ID RELAXATION
AB We present the protocol for the measurement and analysis of dark-state exchange saturation transfer (DEST), a novel solution NMR method for characterizing, at atomic resolution, the interaction between an NMR-'visible' free species and an NMR-'invisible' species transiently bound to a very high-molecular-weight (>1 MDa) macromolecular entity. The reduced rate of reorientational motion in the bound state that precludes characterization by traditional NMR methods permits the observation of DEST. N-15-DEST profiles are measured on a sample comprising the dark state in exchange with an NMR-visible species; in addition, the difference (Delta R-2) in N-15 transverse relaxation rates between this sample and a control sample comprising only the NMR-visible species is also obtained. The N-15-DEST and Delta R-2 data for all residues are then fitted simultaneously to the McConnell equations for various exchange models describing the residue-specific dynamics in the bound state(s) and the interconversion rate constants. Although the length of the experiments depends strongly on sample conditions, approximately 1 week of NMR spectrometer time was sufficient for full characterization of samples of amyloid-beta (A beta) at concentrations of similar to 100 mu M.
C1 [Fawzi, Nicolas L.; Ying, Jinfa; Clore, G. Marius] NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA.
[Torchia, Dennis A.] US Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Fawzi, Nicolas/E-2555-2013; Clore, G. Marius/A-3511-2008
OI Fawzi, Nicolas/0000-0001-5483-0577; Clore, G. Marius/0000-0003-3809-1027
FU NIDDK/NIH
FX We thank D. Libich for helpful comments. This work was supported by the
intramural program of NIDDK/NIH and the AIDS Targeted Antiviral Program
of the NIH Director (to G.M.C.).
NR 12
TC 21
Z9 21
U1 7
U2 53
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 AUG
PY 2012
VL 7
IS 8
BP 1523
EP 1533
DI 10.1038/nprot.2012.077
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 979UK
UT WOS:000306845200008
PM 22814391
ER
PT J
AU Cleeland, CS
Allen, JD
Roberts, SA
Brell, JM
Giralt, SA
Khakoo, AY
Kirch, RA
Kwitkowski, VE
Liao, ZX
Skillings, J
AF Cleeland, Charles S.
Allen, Jeff D.
Roberts, Samantha A.
Brell, Joanna M.
Giralt, Sergio A.
Khakoo, Aarif Y.
Kirch, Rebecca A.
Kwitkowski, Virginia E.
Liao, Zhongxing
Skillings, Jamey
TI Reducing the toxicity of cancer therapy: recognizing needs, taking
action
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID CLINICAL-PRACTICE GUIDELINES; AMERICAN SOCIETY; RADIATION-THERAPY;
PROSTATE-CANCER; ADVERSE EVENTS; TARGETED THERAPIES; SAFETY ASSESSMENT;
MYELOID-LEUKEMIA; BREAST-CANCER; LUNG-CANCER
AB Our understanding of the biology of cancer and the application of this knowledge to cancer treatment has greatly outpaced what we know of the biology underlying the symptoms and toxic effects that therapies produce. These adverse effects of therapy cause substantial discomfort and distress to patients and their families, limit treatment tolerability and can persist indefinitely in post-treatment survivorship. Despite these concerns, little research effort is targeted at documenting the nature of these effects. Similarly, limited efforts are being made in the drug-development arena to identify or develop treatments that might prevent or reduce toxicities. A panel of clinicians and researchers as well as representatives from advocacy groups, federal agencies and the pharmaceutical industry was convened to identify gaps in cancer treatment toxicity research and to provide direction for future action. With an emphasis on coordinating multidisciplinary efforts, this panel has presented a strategy to increase funding for the field and develop a coherent research agenda. Cleeland, C. S. et al. Nat. Rev. Clin. Oncol. 9, 471-478 (2012); published online 3 July 2012; doi:10.1038/nrclinonc.2012.99
C1 [Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Liao, Zhongxing] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Allen, Jeff D.; Roberts, Samantha A.] Friends Canc Res, Arlington, VA 22202 USA.
[Brell, Joanna M.] NCI, Community Oncol & Prevent Trials Res Grp, Rockville, MD 20892 USA.
[Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Serv, New York, NY 10065 USA.
[Khakoo, Aarif Y.] Amgen Inc, Metab Disorders, Res, San Francisco, CA 94080 USA.
[Kirch, Rebecca A.] Amer Canc Soc Inc, Qual Life & Survivorship, Washington, DC 20004 USA.
[Kwitkowski, Virginia E.] US FDA, Off Hematol Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Skillings, Jamey] Pfizer Inc, Pfizer Med Affairs, New York, NY 10017 USA.
RP Cleeland, CS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA.
EM ccleeland@mdanderson.org
FU C. Stratton Hill Colloquium on Pain and Its Relief
FX The authors thank Tim Ahles (American Association for Cancer Research
Survivorship Task Force, New York, NY, USA), Ann O'Mara (National Cancer
Institute [NCI], Bethesda, MD, USA), Jamie H. Von Roenn (ASCO, Chicago,
IL, USA), Elaine B. Yu (Genentech, San Francisco, CA, USA) and Nora
Janjan (National Center for Policy Analysis, Dallas, TX, USA) for their
insightful comments during the drafting of this article. We also
acknowledge Jeanie F. Woodruff for editorial assistance, and M.
Catherine Rodgers for administrative assistance (both at The University
of Texas MD Anderson Cancer Center, Houston, TX, USA). The authors wish
to acknowledge the overall contribution of those who participated in and
contributed to the March 2011 colloquium entitled Developing Strategies
for Reducing Cancer Treatment-Related Toxicities and Symptoms in
Houston, TX, USA: Lyndah K. Dreiling (Amgen, Thousand Oaks, CA, USA),
Marilee Duffield (Alere Health, Marietta, GA, USA), Robert F. Gagel (The
University of Texas MD Anderson Cancer Center, Houston, TX, USA), Mark
Gorman (National Coalition for Cancer Survivorship, Silver Spring, MD,
USA), Amy Guo (Novartis, East Hanover, NJ, USA), Carol A. Hahn (American
Society for Therapeutic Radiation Oncology, Durham, NC, USA), Joan S.
McClure (National Comprehensive Cancer Network, Fort Washington, PA,
USA), Andrew Miller (Lance Armstrong Foundation, Austin, TX, USA),
Scarlott K. Mueller (Oncology Nursing Society Foundation, Pittsburgh,
PA, USA), Robert Z. Orlowski (The University of Texas MD Anderson Cancer
Center, Houston, TX, USA), Lorna Patrick (NCI, Rockville, MD, USA),
Ellen B. Smith (Texas Oncology, Austin, TX, USA), Mark Stephens
(National Patient Advocate Foundation, Washington, DC, USA), Steve G.
Waguespack (The University of Texas MD Anderson Cancer Center, Houston,
TX, USA), Robert A. Warriner III (patient advocate and Diversified
Clinical Services, Spring, TX, USA) and Armin D. Weinberg (Baylor
College of Medicine, Houston, TX, USA). Funding support for the meeting
was provided by the C. Stratton Hill Colloquium on Pain and Its Relief.
The opinions expressed in this article are those of the panellists and
do not constitute a policy position of the NIH, National Cancer
Institute, US Department of Health and Human Services or the US
government.
NR 81
TC 31
Z9 32
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD AUG
PY 2012
VL 9
IS 8
BP 471
EP 478
DI 10.1038/nrclinonc.2012.99
PG 8
WC Oncology
SC Oncology
GA 979WH
UT WOS:000306852700007
PM 22751283
ER
PT J
AU Zhan, B
Santiago, H
Keegan, B
Gillespie, P
Xue, J
Bethony, J
de Oliveira, LM
Jiang, D
Diemert, D
Xiao, SH
Jones, K
Feng, X
Hotez, PJ
Bottazzi, ME
AF Zhan, B.
Santiago, H.
Keegan, B.
Gillespie, P.
Xue, J.
Bethony, J.
de Oliveira, L. M.
Jiang, D.
Diemert, D.
Xiao, S. -H.
Jones, K.
Feng, X.
Hotez, P. J.
Bottazzi, M. E.
TI Fusion of Na-ASP-2 with human immunoglobulin Fc gamma abrogates
histamine release from basophils sensitized with anti-Na-ASP-2 IgE
SO PARASITE IMMUNOLOGY
LA English
DT Article
DE allergy; Fc?RIIb; FceRI; hookworm; IgE; Na-ASP-2; Necator americanus;
vaccine
ID ANCYLOSTOMA-SECRETED PROTEIN; HAMSTERS MESOCRICETUS-AURATUS; MAST-CELL
ACTIVATION; NECATOR-AMERICANUS; HOOKWORM INFECTION; NEGATIVE REGULATION;
BIOCHEMICAL-CHARACTERIZATION; HELMINTH INFECTIONS; IMMUNE-RESPONSES;
PHOSPHATASE SHIP
AB Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N.similar to americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fc?/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fc?1 that targets the negative signalling receptor Fc?RIIb expressed on pro-allergic cells. The chimeric recombinant Fc?/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fc?/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fc?/Na-ASP-2 formulated with Alhydrogel (R) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N.similar to americanus L3 challenge as native Na-ASP-2.
C1 [Zhan, B.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat & Trop Med, Sabin Vaccine Inst, Houston, TX 77030 USA.
[Zhan, B.; Keegan, B.; Gillespie, P.; Jones, K.; Hotez, P. J.; Bottazzi, M. E.] Baylor Coll Med, Dept Pediat, Sect Pediat Trop Med, Houston, TX 77030 USA.
[Zhan, B.; Keegan, B.; Gillespie, P.; Jones, K.; Hotez, P. J.; Bottazzi, M. E.] Baylor Coll Med, Dept Mol Virol & Microbiol, Sect Pediat Trop Med, Houston, TX 77030 USA.
[Zhan, B.; Keegan, B.; Gillespie, P.; Jones, K.; Hotez, P. J.; Bottazzi, M. E.] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA.
[Zhan, B.; Keegan, B.; Gillespie, P.; Jones, K.; Hotez, P. J.; Bottazzi, M. E.] Texas Childrens Hosp, Ctr Vaccine Dev, Houston, TX 77030 USA.
[Santiago, H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Xue, J.; Xiao, S. -H.] Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, Shanghai, Peoples R China.
[Bethony, J.; de Oliveira, L. M.; Jiang, D.; Diemert, D.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA.
[Feng, X.] Jilin Med Coll, Dept Parasitol, Changchun, Jilin, Peoples R China.
RP Zhan, B (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat & Trop Med, Sabin Vaccine Inst, 1102 Bates St,Ste 550, Houston, TX 77030 USA.
EM bzhan@bcm.edu
RI Vacinas, Inct/J-9431-2013;
OI Hotez, Peter/0000-0001-8770-1042
FU Sabin Vaccine Institute's Human Hookworm Vaccine Initiative; Bill &
Melinda Gates Foundation
FX This study was supported by the Sabin Vaccine Institute's Human Hookworm
Vaccine Initiative, which is funded by the Bill & Melinda Gates
Foundation. We thank Dr. Ke Zhang from UCLA for his technical advice and
support.
NR 39
TC 10
Z9 10
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0141-9838
J9 PARASITE IMMUNOL
JI Parasite Immunol.
PD AUG-SEP
PY 2012
VL 34
IS 8-9
BP 404
EP 411
DI 10.1111/j.1365-3024.2012.01371.x
PG 8
WC Immunology; Parasitology
SC Immunology; Parasitology
GA 983FT
UT WOS:000307105500002
PM 22651670
ER
PT J
AU Perry, JSA
Han, S
Xu, QG
Herman, ML
Kennedy, LB
Csako, G
Bielekova, B
AF Perry, Justin S. A.
Han, Sungpil
Xu, Quangang
Herman, Matthew L.
Kennedy, Lucy B.
Csako, Gyorgy
Bielekova, Bibiana
TI Inhibition of LTi Cell Development by CD25 Blockade Is Associated with
Decreased Intrathecal Inflammation in Multiple Sclerosis
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID TISSUE-INDUCER CELLS; NATURAL-KILLER-CELLS; INNATE LYMPHOID-CELLS;
CENTRAL-NERVOUS-SYSTEM; B-CELL; T-CELL; MENINGEAL INFLAMMATION;
RECEPTOR-ALPHA; IL-2 RECEPTOR; NK CELLS
AB Genetic polymorphisms in the interleukin-2 receptor alpha (IL-2R alpha) chain (CD25) locus are associated with several human autoimmune diseases, including multiple sclerosis (MS). Blockade of CD25 by the humanized monoclonal antibody daclizumab decreases MS-associated inflammation but has surprisingly limited direct inhibitory effects on activated T cells. The present study describes unexpected effects of daclizumab therapy on innate lymphoid cells (ILCs). The number of circulating retinoic acid receptor-related orphan receptor gamma t-positive ILCs, which include lymphoid tissue inducer (LTi) cells, was found to be elevated in untreated MS patients compared to healthy subjects. Daclizumab therapy not only decreased numbers of ILCs but also modified their phenotype away from LTi cells and toward a natural killer (NK) cell lineage. Mechanistic studies indicated that daclizumab inhibited differentiation of LTi cells from CD34(+) hematopoietic progenitor cells or c-kit(+) ILCs indirectly, steering their differentiation toward immunoregulatory CD56(bright) NK cells through enhanced intermediate-affinity IL-2 signaling. Because adult LTi cells may retain lymphoid tissue-inducing capacity or stimulate adaptive immune responses, we indirectly measured intrathecal inflammation in daclizumab-treated MS patients by quantifying the cerebrospinal fluid chemokine (C-X-C motif) ligand 13 and immunoglobulin G index. Both of these inflammatory biomarkers were inhibited by daclizumab treatment. Our study indicates that ILCs are involved in the regulation of adaptive immune responses, and their role in human autoimmunity should be investigated further, including their potential as therapeutic targets.
C1 [Perry, Justin S. A.; Han, Sungpil; Xu, Quangang; Herman, Matthew L.; Kennedy, Lucy B.; Bielekova, Bibiana] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Han, Sungpil] Pusan Natl Univ, Sch Med, Yangsan 626870, South Korea.
[Xu, Quangang] Chinese Peoples Liberat Army Gen Hosp, Dept Neurol, Beijing 100853, Peoples R China.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
OI Han, Sungpil/0000-0002-4674-7682
FU Intramural Research Program of the NINDS; NIH Clinical Center
FX We thank A. Kashani for apheresis processing, the Neuroimmunology Branch
(NIB) nursing staff and clinicians for care of patients and coordination
of apheresis and blood collection, and J. Martin for technical
assistance. Above all, we are grateful to all patients participating in
NIB protocols whose samples contributed to this study. Funding: This
research was supported by the Intramural Research Program of the NINDS
and NIH Clinical Center. Author contributions: B.B. developed the
concept of the study and supervised the project. J.S.A.P., S.H., and
B.B. designed the experiments. J.S.A.P., S.H., Q.X., M.L.H., L.B.K.,
G.C., and B.B. performed the experiments and analyzed the data.
J.S.A.P., S.H., and B.B. wrote the paper. Competing interests: B.B. is a
coinventor on NIH patents related to daclizumab therapy and, as such,
has received royalty payments based on license to U.S. patents 7,575,742
and 7,258,859 (and patent applications claiming priority to these
patents) and other National Stage patents and patent applications
claiming priority to PCT/US2002/038290 or PCT/US2003/020428. The other
authors declare that they have no competing interests.
NR 48
TC 30
Z9 30
U1 0
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 1
PY 2012
VL 4
IS 145
AR 145ra106
DI 10.1126/scitranslmed.3004140
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 984AJ
UT WOS:000307159500005
PM 22855463
ER
PT J
AU Huang, JF
Chen, SF
Lu, XF
Zhao, Q
Rao, DC
Jaquish, CE
Hixson, JE
Chen, JC
Wang, LY
Cao, J
Li, JX
Li, HF
He, J
Liu, DP
Gu, DF
AF Huang, Jianfeng
Chen, Shufeng
Lu, Xiangfeng
Zhao, Qi
Rao, Dabeeru C.
Jaquish, Cashell E.
Hixson, James E.
Chen, Jichun
Wang, Laiyuan
Cao, Jie
Li, Jianxin
Li, Hongfan
He, Jiang
Liu, De-Pei
Gu, Dongfeng
TI Polymorphisms of ACE2 are Associated with Blood Pressure Response to
Cold Pressor Test: The GenSalt Study
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE angiotensin converting enzyme 2; apelin; apelin receptor; blood
pressure; cold pressor test; hypertension
ID ANGIOTENSIN-CONVERTING ENZYME; CHINESE POPULATION; GENETIC INFLUENCES;
IN-VIVO; APELIN; HYPERTENSION; RECEPTOR; SYSTEM; APJ; CARBOXYPEPTIDASE
AB BACKGROUND
Increased blood pressure (BP) reactivity to cold pressor test (CPT) is a risk factor for hypertension. Genetic factors may influence the variation of BP response to CPT among individuals. We explored the association of genetic variants in the apelin system genes (APLN, APLNR and ACE2) and BP response to CPT in a Chinese population.
METHODS
A total of 1,998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed a CPT. The percentage changes of BP right after the end of ice-water immersion were used as the measurement of BP responses to CPT. Twenty-two single nucleotide polymorphisms (SNPs) were selected and genotyped, including both tag and potential functional SNPs of the APLN, APLNR, and ACE2 genes. A mixed-effect linear model was used to assess the association between SNPs and BP responses to CPT.
RESULTS
In women, three SNPs (rs1514283, rs4646176, and rs879922) of the ACE2 gene were significantly associated with the diastolic BP (DBP) response to CPT in the general and recessive genetic models after adjustment for multiple testing (all false discovery rate q < 0.05). There were no significant associations of polymorphisms in APLN and APLNR genes with BP responses to CPT.
CONCLUSIONS
Our study identified genetic variants in the ACE2 gene that were significantly associated with DBP responses to cold stress in the Chinese female population. Future studies are warranted to confirm these findings.
C1 [Huang, Jianfeng; Chen, Shufeng; Lu, Xiangfeng; Chen, Jichun; Wang, Laiyuan; Cao, Jie; Li, Jianxin; Li, Hongfan; Gu, Dongfeng] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Natl Ctr Cardiovasc Dis, Dept Evidence Based Med,Fuwai Hosp, Beijing 100730, Peoples R China.
[Huang, Jianfeng; Chen, Shufeng; Lu, Xiangfeng; Chen, Jichun; Wang, Laiyuan; Cao, Jie; Li, Jianxin; Li, Hongfan; Gu, Dongfeng] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Natl Ctr Cardiovasc Dis, Div Populat Genet,Fuwai Hosp, Beijing 100730, Peoples R China.
[Huang, Jianfeng; Chen, Shufeng; Lu, Xiangfeng; Chen, Jichun; Wang, Laiyuan; Cao, Jie; Li, Jianxin; Li, Hongfan; Liu, De-Pei; Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Zhao, Qi; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jaquish, Cashell E.] NHLBI, Div Cardiovasc Dis Sci, Bethesda, MD 20892 USA.
[Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Liu, De-Pei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China.
[Gu, Dongfeng] Chinese Natl Human Genome Ctr, Beijing, Peoples R China.
RP Huang, JF (reprint author), Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Natl Ctr Cardiovasc Dis, Dept Evidence Based Med,Fuwai Hosp, Beijing 100730, Peoples R China.
EM jianfhuang@sina.com
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by research grants (U01HL072507, R01HL087263, and R01HL090682)
from the National Heart, Lung, and Blood Institute, National Institutes
of Health, Bethesda, Maryland.
NR 33
TC 5
Z9 5
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD AUG
PY 2012
VL 25
IS 8
BP 937
EP 942
DI 10.1038/ajh.2012.61
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 977AI
UT WOS:000306628100016
PM 22647782
ER
PT J
AU Madeo, AC
O'Brien, KE
Bernhardt, BA
Biesecker, BB
AF Madeo, Anne C.
O'Brien, Kathleen E.
Bernhardt, Barbara A.
Biesecker, Barbara B.
TI Factors associated with perceived uncertainty among parents of children
with undiagnosed medical conditions
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE uncertainty; rare diseases; perceived control; parents; undiagnosed
ID PERSONAL CONTROL; HEALTH-CARE; DISPOSITIONAL OPTIMISM; DIAGNOSIS;
MOTHERS; CANCER; DISABILITIES; LIFE
AB Uncertainty is a pervasive characteristic of illness. Yet little is known about the individual or situational factors that contribute to perceptions of uncertainty. The present study aims to examine the factors that contribute to perceived uncertainty among parents of a child with an undiagnosed condition. Two hundred sixty-six parents of a child, or children, affected by an undiagnosed medical condition for at least 2 years completed an electronically administered mixed-methods survey assessing theoretical predictors of perceived uncertainty. Multivariate linear regression analyses were used to identify the relationship of key variables to perceived uncertainty. Parents' perceived control and optimism were negatively associated with uncertainty (B?=?-4.044, P?=?0.001, B?=?-0.477, P?=?0.05). Subjective disease severity was positively associated with perceived uncertainty (B?=?1.797, P?=?0.05). Our findings suggest that parents who experience greater uncertainty feel less control over their child's medical condition, which may lead to less effective coping and poorer adaptation. Parents who are less optimistic or who perceive their child's disease as more severe may benefit most from interventions that target situations where parents perceive the least control, thereby enhancing coping and ultimately, adaptation. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Madeo, Anne C.; O'Brien, Kathleen E.; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Bernhardt, Barbara A.] Univ Penn, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
RP Madeo, AC (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Room B1B36, Bethesda, MD 20892 USA.
EM acmadeo@gmail.com
RI Madeo, Anne/K-2880-2012
FU Intramural Research Program, National Human Genome Research Institute,
National Institutes of Health
FX Grant sponsor: Intramural Research Program, National Human Genome
Research Institute, National Institutes of Health.
NR 38
TC 14
Z9 15
U1 1
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2012
VL 158A
IS 8
BP 1877
EP 1884
DI 10.1002/ajmg.a.35425
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 977IT
UT WOS:000306651400011
PM 22711240
ER
PT J
AU Hong, NJL
Pandalai, PK
Hornick, JL
Shekar, PS
Harmon, DC
Chen, YL
Butrynski, JE
Baldini, EH
Raut, CP
AF Hong, Nicole J. Look
Pandalai, Prakash K.
Hornick, Jason L.
Shekar, Prem S.
Harmon, David C.
Chen, Yen-Lin
Butrynski, James E.
Baldini, Elizabeth H.
Raut, Chandrajit P.
TI Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution
Experience
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 92nd Annual Meeting of the New-England-Surgical-Society
CY SEP 23-25, 2011
CL Bretton Woods, NH
SP New England Surg Soc
ID HEART-TRANSPLANTATION; SURGICAL-TREATMENT; TERM SURVIVAL; TUMORS;
SARCOMAS; PACLITAXEL; DOCETAXEL; DISEASE
AB To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).
This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival.
Data from 18 patients (78 % male) were reviewed. Sixteen patients (89 %) had AS originating in the right atrium. At diagnosis, eight patients (44 %) had localized/locally advanced disease and ten patients (56 %) had metastatic disease. Initial treatment strategies included resection (44 %), chemotherapy (39 %), and radiotherapy (11 %). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12 months. Median overall survival (OS) was 13 months for the entire cohort; median OS was 19.5 months for those presenting with localized/locally advanced AS and 6 months for those with metastatic disease at presentation (p = 0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5 months, p = 0.01).
Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.
C1 [Hong, Nicole J. Look; Raut, Chandrajit P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Surg Oncol,Brigham & Womens Hosp,Ctr Sarcoma, Boston, MA 02115 USA.
[Pandalai, Prakash K.] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA.
[Hornick, Jason L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Brigham & Womens Hosp,Ctr Sarcoma & B, Boston, MA 02115 USA.
[Shekar, Prem S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA.
[Harmon, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02115 USA.
[Chen, Yen-Lin] Harvard Univ, Sch Med, Div Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Butrynski, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol,Brigham & Womens Hosp,Ctr Sarcoma &, Boston, MA 02115 USA.
[Baldini, Elizabeth H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Radiat Oncol,Brigham & Womens Hosp,Ctr Sarcom, Boston, MA 02115 USA.
RP Hong, NJL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Surg Oncol,Brigham & Womens Hosp,Ctr Sarcoma, 44 Binney St, Boston, MA 02115 USA.
EM n.lookhong@utoronto.ca
NR 38
TC 11
Z9 12
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD AUG
PY 2012
VL 19
IS 8
BP 2707
EP 2715
DI 10.1245/s10434-012-2334-2
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA 979BD
UT WOS:000306789000040
ER
PT J
AU Sancho, V
Nuche-Berenguer, B
Jensen, RT
AF Sancho, Veronica
Nuche-Berenguer, Bernardo
Jensen, R. T.
TI The Src kinase Yes is activated in pancreatic acinar cells by
gastrointestinal hormones/neurotransmitters, but not pancreatic growth
factors, which stimulate its association with numerous other signaling
molecules
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Src; Yes activation; Pancreatic acinus; CCK; Signaling; Pancreatic
growth factor
ID FOCAL ADHESION KINASE; FAMILY TYROSINE KINASES; APICAL PLASMA-MEMBRANE;
PKC-DELTA; PHOSPHOLIPASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR
OCCUPATION; IN-VIVO; CHOLECYSTOKININ; PROTEIN
AB For growth factors, cytokines. G-protein-coupled receptors and numerous other stimuli, the Src Family of kinases (SFK) play a central signaling role. SFKs also play an important role in pancreatic acinar cell function including metabolism, secretion, endocytosis, growth and cytoskeletal integrity, although the specific SFKs involved are not fully known. In the present study we used specific antibodies for the SFK, Yes, to determine its presence, activation by pancreatic secretagogues or growth factors, and interaction with cellular signaling cascades mediated by CCK in which Yes participates in to cause acinar cell responses. Yes was identified in acini and secretagogues known to activate phospholipase C (PLC) [CCK, carbachol, bombesin] as well as post-receptor stimulants activating PKC [TPA] or mobilizing cellular calcium [thapsigargin/calcium ionophore (A23187)] each activated Yes. Secretin, which activates adenylate cyclase did not stimulate Yes, nor did pancreatic growth factors. CCK activation of Yes required both high- and low-affinity CCK1-receptor states. TPA-/CCK-stimulated Yes activation was completely inhibited by thapsigargin and the PKC inhibitor, GF109203X. CCK/TPA stimulated the association of Yes with focal adhesion kinases (Pyk2, FAK) and its autophosphorylated forms (pY397FAK, pY402Pyk2). Moreover, CCK/TPA stimulated Yes interacted with a number of other signaling proteins, including Shc, PKD, p130(Cas), PI3K and PTEN. This study demonstrates that in rat pancreatic acini, the SFK member Yes is expressed and activated by CCK and other gastrointestinal hormones/neurotransmitters. Because its activation results in the direct activation of many cellular signaling cascades that have been shown to mediate CCK's effect in acinar cell function our results suggest that it is one of the important pancreatic SFKs mediating these effects. Published by Elsevier B.V.
C1 [Sancho, Veronica; Nuche-Berenguer, Bernardo; Jensen, R. T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Jensen, RT (reprint author), NIH NIDDK DDB, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
FU NIDDK, NIH
FX This work is partially supported by the Intramural Research Program of
the NIDDK, NIH.
NR 61
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD AUG
PY 2012
VL 1823
IS 8
BP 1285
EP 1294
DI 10.1016/j.bbamcr.2012.05.015
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 976YY
UT WOS:000306624500007
PM 22617836
ER
PT J
AU Miyake, K
Bekisz, J
Zhao, T
Clark, CR
Zoon, KC
AF Miyake, Kotaro
Bekisz, Joseph
Zhao, Tongmao
Clark, Christopher R.
Zoon, Kathryn C.
TI Apoptosis-inducing factor (AIF) is targeted in IFN-alpha 2a-induced
Bid-mediated apoptosis through Bak activation in ovarian cancer cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE IFN-alpha; Apoptosis; Mitochondria; AIF; Bid; Bak
ID ALPHA-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; BCL-2 FAMILY-MEMBERS;
INTERFERON-ALPHA; IFN-ALPHA; MITOCHONDRIAL CONTROL; PANCREATIC-CANCER;
SIGNALING PATHWAY; DEATH; INHIBITION
AB Previously we have shown that interferon (IFN)-alpha induced apoptosis is predominantly mediated by the upregulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) via the caspase-8 pathway. It was also shown that recruitment of mitochondria in IFN-alpha induced apoptosis involves the cleavage of BH3 interacting domain death agonist (Bid) to truncated Bid (tBid). In the present study, we demonstrate that tBid induced by IFN-alpha 2a activates mitochondrial Bak to trigger the loss of mitochondrial membrane integrity, consequently causing release of apoptosis-inducing factor (AIF) in ovarian cancer cells, OVCAR3. AIF translocates from the mitochondria to the nucleus and induces nuclear fragmentation and cell death. Both a small molecule Bid inhibitor (BI-6C9) or Bid-RNA interference (RNAi) preserved mitochondrial membrane potential, prevented nuclear translocation of AIF, and abrogated IFN-alpha 2a-induced cell death. Cell death induced by tBid was inhibited by AIF-RNAi, indicating that caspase-independent AIF signaling is the main pathway through which Bid mediates cell death. This was further supported by experiments showing that BI-6C9 did not prevent the release of cytochrome c from mitochondria to cytosol, while the release of AIF was prevented. In conclusion, IFN-alpha 2a-induced apoptosis is mediated via the mitochondria-associated pathway involving the cleavage of Bid followed by AIF release that involves Bak activation and translocation of AIF from the mitochondria to the nucleus in OVCAR3 cells. Published by Elsevier B.V.
C1 [Miyake, Kotaro; Bekisz, Joseph; Zhao, Tongmao; Clark, Christopher R.; Zoon, Kathryn C.] NIAID, Div Intramural Res, NIH, Cytokine Biol Sect, Bethesda, MD 20892 USA.
RP Zoon, KC (reprint author), NIAID, Div Intramural Res, NIH, Cytokine Biol Sect, Bldg 33 Rm 2N09G-2,33 N Dr, Bethesda, MD 20892 USA.
EM kzoon@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We are grateful to members of Dr. Owen Schwartz's laboratory,
particularly S. Ganesan and S. Becker for their help with the confocal
microscopy. We also thank the other members of the Kathryn C. Zoon's
laboratory, particularly Dr. Takaya Tsuno for many helpful discussions
and suggestions. This work was supported by the Intramural Research
Program of the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.
NR 40
TC 12
Z9 14
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD AUG
PY 2012
VL 1823
IS 8
BP 1378
EP 1388
DI 10.1016/j.bbamcr.2012.05.031
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 976YY
UT WOS:000306624500015
PM 22683989
ER
PT J
AU van Iersel, MP
Villeger, AC
Czauderna, T
Boyd, SE
Bergmann, FT
Luna, A
Demir, E
Sorokin, A
Dogrusoz, U
Matsuoka, Y
Funahashi, A
Aladjem, MI
Mi, HY
Moodie, SL
Kitano, H
Le Novere, N
Schreiber, F
AF van Iersel, Martijn P.
Villeger, Alice C.
Czauderna, Tobias
Boyd, Sarah E.
Bergmann, Frank T.
Luna, Augustin
Demir, Emek
Sorokin, Anatoly
Dogrusoz, Ugur
Matsuoka, Yukiko
Funahashi, Akira
Aladjem, Mirit I.
Mi, Huaiyu
Moodie, Stuart L.
Kitano, Hiroaki
Le Novere, Nicolas
Schreiber, Falk
TI Software support for SBGN maps: SBGN-ML and LibSBGN
SO BIOINFORMATICS
LA English
DT Article
ID LAYOUT EXTENSION; SYSTEMS BIOLOGY; SBML; NETWORKS; REPRESENTATION;
VISUALIZATION; PATHWAYS; EXCHANGE; DIAGRAMS; LIBRARY
AB Motivation: LibSBGN is a software library for reading, writing and manipulating Systems Biology Graphical Notation (SBGN) maps stored using the recently developed SBGN-ML file format. The library (available in C++ and Java) makes it easy for developers to add SBGN support to their tools, whereas the file format facilitates the exchange of maps between compatible software applications. The library also supports validation of maps, which simplifies the task of ensuring compliance with the detailed SBGN specifications. With this effort we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner.
C1 [van Iersel, Martijn P.; Moodie, Stuart L.; Le Novere, Nicolas] EMBL European Bioinformat Inst, Hinxton, England.
[van Iersel, Martijn P.] NCSB, Amsterdam, Netherlands.
[van Iersel, Martijn P.] Univ Maastricht, Dept Bioinformat BiGCaT, Maastricht, Netherlands.
[Villeger, Alice C.] Univ Manchester, Fac Engn & Phys Sci, Sch Comp Sci, Manchester, Lancs, England.
[Czauderna, Tobias; Schreiber, Falk] Leibniz Inst Plant Genet & Crop Plant Res IPK, Gatersleben, Germany.
[Boyd, Sarah E.] Monash Univ, Fac Sci, Sch Math Sci, Melbourne, Vic 3004, Australia.
[Bergmann, Frank T.] CALTECH, Pasadena, CA 91125 USA.
[Luna, Augustin] NCI, Bethesda, MD 20892 USA.
[Luna, Augustin] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Demir, Emek] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Sorokin, Anatoly] Inst Cell Biophys RAS, Pushchino, Russia.
[Dogrusoz, Ugur] Bilkent Univ, Dept Comp Engn, Ankara, Turkey.
[Matsuoka, Yukiko; Kitano, Hiroaki] Syst Biol Inst, Tokyo, Japan.
[Funahashi, Akira] Keio Univ, Dept Biosci & Informat, Yokohama, Kanagawa 223, Japan.
[Aladjem, Mirit I.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Mi, Huaiyu; Kitano, Hiroaki] Okinawa Inst Sci & Technol, Okinawa, Japan.
[Schreiber, Falk] Univ Halle Wittenberg, Fac Nat Sci 2, Inst Comp Sci, Halle, Germany.
RP van Iersel, MP (reprint author), EMBL European Bioinformat Inst, Hinxton, England.
EM sbgn-libsbgn@lists.sourceforge.net
RI Boyd, Sarah/I-9047-2012; Funahashi, Akira/C-4923-2014; Sorokin,
Anatoly/A-9090-2008; Aladjem, Mirit/G-2169-2010; van Iersel,
Martijn/E-9105-2010;
OI Sorokin, Anatoly/0000-0002-0047-0606; Aladjem,
Mirit/0000-0002-1875-3110; Funahashi, Akira/0000-0003-0605-239X; van
Iersel, Martijn/0000-0002-5877-4338; Le Novere,
Nicolas/0000-0002-6309-7327; Boyd, Sarah/0000-0002-7264-8602; Bergmann,
Frank/0000-0001-5553-4702
FU Biotechnology and Biological Sciences Research Council (BBSRC);
Netherlands Consortium for Systems Biology (NCSB); Netherlands Genomics
Initiative/Netherlands Organisation for Scientific Research; EU; NIH;
National Cancer Institute; Center for Cancer Research; German Ministry
of Education and Research (BMBF)
FX This work was in part supported by the Biotechnology and Biological
Sciences Research Council (BBSRC); the Netherlands Consortium for
Systems Biology (NCSB), which is part of the Netherlands Genomics
Initiative/Netherlands Organisation for Scientific Research; BioPreDyn
which is a grant within the Seventh Framework Programme of the EU, the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; and the German Ministry of Education and
Research (BMBF).
NR 16
TC 25
Z9 25
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 1
PY 2012
VL 28
IS 15
BP 2016
EP 2021
DI 10.1093/bioinformatics/bts270
PG 6
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 977TA
UT WOS:000306686400010
PM 22581176
ER
PT J
AU Saligan, LN
Kim, HS
AF Saligan, L. N.
Kim, H. S.
TI A systematic review of the association between immunogenomic markers and
cancer-related fatigue
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Review
ID QUALITY-OF-LIFE; NECROSIS-FACTOR-ALPHA; HUMAN BREAST-CANCER; CYTOKINE
LEVELS; INFLAMMATORY BIOMARKERS; TUMOR MICROENVIRONMENT; INTERLEUKIN-1
FAMILY; PERSISTENT FATIGUE; GENE POLYMORPHISMS; SLEEP DISTURBANCE
AB Fatigue, which is one of the most commonly reported symptoms in cancer, can negatively impact the functional status and the health-related quality of life of individuals. This paper systematically reviews 34 studies to determine patterns of associations between immunogenomic markers and levels of cancer-related fatigue (CRF). Findings from the longitudinal studies revealed that elevated fatigue symptoms especially of women with early stages of breast cancer were associated with high levels of neutrophil/monocyte, IL-1ra, and IL-6 during radiation therapy; high levels of CD4+. IL-1 beta, and IL-6 with stressing stimuli; high levels of IL-1 beta during chemotherapy; low NK cell levels after chemotherapy; and presence of homozygous IL-6 and TNF alleles. In the cross-sectional studies, associations between levels of fatigue and immune/inflammatory markers were not consistently found, especially when covariates such as BM!, ethnicity, menopausal status, and educational level were controlled in the statistical analyses. However, a number of genomic markers were observed to be elevated mostly in fatigued breast cancer survivors in the cross-sectional studies. Gaps in knowledge and recommendations for future research are discussed. Published by Elsevier Inc.
C1 [Saligan, L. N.; Kim, H. S.] NINR, NIH, Bethesda, MD 20892 USA.
RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 10,Room 2-1339, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
FU Intramural NIH HHS [Z99 NR999999, ZIA NR000020-01]
NR 63
TC 53
Z9 53
U1 1
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2012
VL 26
IS 6
BP 830
EP 848
DI 10.1016/j.bbi.2012.05.004
PG 19
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 978VE
UT WOS:000306773100002
PM 22595751
ER
PT J
AU Doroshow, JH
AF Doroshow, James H.
TI Dexrazoxane for the Prevention of Cardiac Toxicity and Treatment of
Extravasation Injury from the Anthracycline Antibiotics
SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY
LA English
DT Review
DE Dexrazoxane; anthracycline; doxorubicin; oxidative stress; iron;
chelator; cardiac toxicity; extravasation injury
ID ADVANCED BREAST-CANCER; DOXORUBICIN-INDUCED CARDIOMYOPATHY;
CARDIOPROTECTIVE AGENT ICRF-187; ACUTE LYMPHOBLASTIC-LEUKEMIA;
CONGESTIVE-HEART-FAILURE; FREE-RADICAL FORMATION; NITRIC-OXIDE SYNTHASE;
INDUCED CARDIOTOXICITY; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE
AB The cumulative cardiac toxicity of the anthracycline antibiotics and their propensity to produce severe tissue injury following extravasation from a peripheral vein during intravenous administration remain significant problems in clinical oncologic practice. Understanding of the free radical metabolism of these drugs and their interactions with iron proteins led to the development of dexrazoxane, an analogue of EDTA with intrinsic antineoplastic activity as well as strong iron binding properties, as both a prospective cardioprotective therapy for patients receiving anthracyclines and as an effective treatment for anthracycline extravasations. In this review, the molecular mechanisms by which the anthracyclines generate reactive oxygen species and interact with intracellular iron are examined to understand the cardioprotective mechanism of action of dexrazoxane and its ability to protect the subcutaneous tissues from anthracycline-induced tissue necrosis.
C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research
of the National Cancer Institute, National Institutes of Health
FX This work was supported by federal funds from the Division of Cancer
Treatment and Diagnosis, and the Center for Cancer Research of the
National Cancer Institute, National Institutes of Health. The content of
this publication does not necessarily reflect the views or the policies
of the US Department of Health and Human Services nor does the mention
of trade names, commercial products, or organizations imply endorsement
by the US government.
NR 111
TC 6
Z9 6
U1 0
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2010
J9 CURR PHARM BIOTECHNO
JI Curr. Pharm. Biotechnol.
PD AUG
PY 2012
VL 13
IS 10
BP 1949
EP 1956
PG 8
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 979QP
UT WOS:000306835200012
PM 22352729
ER
PT J
AU White, SF
Williams, WC
Brislin, SJ
Sinclair, S
Blair, KS
Fowler, KA
Pine, DS
Pope, K
Blair, RJ
AF White, Stuart F.
Williams, W. Craig
Brislin, Sarah J.
Sinclair, Stephen
Blair, Karina S.
Fowler, Katherine A.
Pine, Daniel S.
Pope, Kayla
Blair, R. James
TI Reduced activity within the dorsal endogenous orienting of attention
network to fearful expressions in youth with disruptive behavior
disorders and psychopathic traits
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; COMMON
STEREOTACTIC SPACE; FACIAL EXPRESSIONS; CONDUCT PROBLEMS;
VISUAL-ATTENTION; GAZE DIRECTION; EYE GAZE; DEVELOPMENTAL ORIGINS;
EMOTIONAL EXPRESSION
AB Using behavioral and blood oxygen level dependent (BOLD) response indices through functional magnetic resonance imaging (fMRI), the current study investigated whether youths with disruptive behavior disorders (conduct disorder and oppositional defiant disorder) plus psychopathic traits (DBD + PT) show aberrant sensitivity to eye gaze information generally and/or whether they show particular insensitivity to eye gaze information in the context of fearful expressions. The participants were 36 children and adolescents (ages 10-17 years); 17 had DBD + PT and 19 were healthy comparison subjects. Participants performed a spatial attention paradigm where spatial attention was cued by eye gaze in faces displaying fearful, angry, or neutral affect. Eye gaze sensitivity was indexed both behaviorally and as BOLD response. There were no group differences in behavioral response: both groups showed significantly faster responses if the target was in the congruent spatial direction indicated by eye gaze. Neither group showed a Congruence x Emotion interaction; neither group showed an advantage from the displayer's emotional expression behaviorally. However, the BOLD response revealed a significant Group x Congruence x Emotion interaction. The comparison youth showed increased activity within the dorsal endogenous orienting network (superior parietal lobule and inferior parietal sulcus) for fearful congruent relative to incongruent trials relative to the youth with DBD + PT. The results are discussed with reference to current models of DBD + PT and possible treatment innovations.
C1 [Blair, R. James] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA.
RP Blair, RJ (reprint author), NIMH, Unit Affect Cognit Neurosci, 9000 Rockville Pike,Bldg 15K,Room 206, Bethesda, MD 20892 USA.
EM blairj@intra.nimh.nih.gov
FU Intramural NIH HHS [Z01 MH002860-04]
NR 68
TC 15
Z9 15
U1 3
U2 16
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD AUG
PY 2012
VL 24
IS 3
SI SI
BP 1105
EP 1116
DI 10.1017/S0954579412000569
PG 12
WC Psychology, Developmental
SC Psychology
GA 977QS
UT WOS:000306680100026
PM 22781874
ER
PT J
AU Metukuri, MR
Zhang, PL
Basantani, MK
Chin, C
Stamateris, RE
Alonso, LC
Takane, KK
Gramignoli, R
Strom, SC
O'Doherty, RM
Stewart, AF
Vasavada, RC
Garcia-Ocana, A
Scott, DK
AF Metukuri, Mallikarjuna R.
Zhang, Pili
Basantani, Mahesh K.
Chin, Connie
Stamateris, Rachel E.
Alonso, Laura C.
Takane, Karen K.
Gramignoli, Roberto
Strom, Stephen C.
O'Doherty, Robert M.
Stewart, Andrew F.
Vasavada, Rupangi C.
Garcia-Ocana, Adolfo
Scott, Donald K.
TI ChREBP Mediates Glucose-Stimulated Pancreatic beta-Cell Proliferation
SO DIABETES
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; CENTER-DOT-MLX; GENE-EXPRESSION; IN-VIVO;
TRANSCRIPTION; PROTEIN; REPLICATION; INDUCTION; MICE; ACTIVATION
AB Glucose stimulates rodent and human beta-cell replication, but the intracellular signaling mechanisms are poorly understood. Carbohydrate response element-binding protein (ChREBP) is a lipogenic glucose-sensing transcription factor with unknown functions in pancreatic beta-cells. We tested the hypothesis that ChREBP is required for glucose-stimulated beta-cell proliferation. The relative expression of ChREBP was determined in liver and beta-cells using quantitative RT-PCR (qRT-PCR), immunoblotting, and immunohistochemistry. Loss- and gain-of-function studies were performed using small interfering RNA and genetic deletion of ChREBP and adenoviral overexpression of ChREBP in rodent and human beta-cells. Proliferation was measured by 5-bromo-2'-deoxyuridine incorporation, [H-3]thymidine incorporation, and fluorescence-activated cell sorter analysis. hi addition, the expression of cell cycle regulatory genes was measured by qRT-PCR and immunoblotting. ChREBP expression was comparable with liver in mouse pancreata and in rat and human islets. Depletion of ChREBP decreased glucose-stimulated proliferation in beta-cells isolated from ChREBP(-/-) mice, in INS-1-derived 832/13 cells, and in primary rat and human beta-cells. Furthermore, depletion of ChREBP decreased the glucose-stimulated expression of cell cycle accelerators. Overexpression of ChREBP amplified glucose-stimulated proliferation in rat and human beta-cells, with concomitant increases in cyclin gene expression. In conclusion, ChREBP mediates glucose-stimulated proliferation in pancreatic beta-cells. Diabetes 61:2004-2015, 2012
C1 [Metukuri, Mallikarjuna R.; Zhang, Pili; Basantani, Mahesh K.; Chin, Connie; Stamateris, Rachel E.; Alonso, Laura C.; Takane, Karen K.; O'Doherty, Robert M.; Stewart, Andrew F.; Vasavada, Rupangi C.; Garcia-Ocana, Adolfo; Scott, Donald K.] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA.
[Metukuri, Mallikarjuna R.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
[Gramignoli, Roberto; Strom, Stephen C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
RP Scott, DK (reprint author), Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA.
EM dks23@pitt.edu
RI Basantani, Mahesh/G-9341-2013;
OI Strom, Stephen/0000-0002-2889-3387
FU National Institutes of Health (NIH) [R56DK065149]; American Diabetes
Association [ADA 7-11-BS-128]; Juvenile Diabetes Research Foundation
(JDRF) [17-2011-598]; NIH [DK077096, DK078060, DKR0155023, DK U-01
89538]; JDRF [34-2008-630, 1-2008-39]
FX This work was supported by the following grants: National Institutes of
Health (NIH) R56DK065149; American Diabetes Association ADA 7-11-BS-128;
Juvenile Diabetes Research Foundation (JDRF) 17-2011-598 (D.K.S.); NIH
DK077096 (A.G.-O.) and NIH DK078060 (R.C.V.); and JDRF 34-2008-630, JDRF
1-2008-39, NIH DKR0155023, and NIH DK U-01 89538 (A.F.S.).
NR 50
TC 42
Z9 43
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 AUG
PY 2012
VL 61
IS 8
BP 2004
EP 2015
DI 10.2337/db11-0802
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 980KC
UT WOS:000306891100016
PM 22586588
ER
PT J
AU Rovner, AJ
Nansel, TR
Mehta, SN
Higgins, LA
Haynie, DL
Laffel, LM
AF Rovner, Alisha J.
Nansel, Tonja R.
Mehta, Sanjeev N.
Higgins, Laurie A.
Haynie, Denise L.
Laffel, Lori M.
TI Development and Validation of the Type 1 Diabetes Nutrition Knowledge
Survey
SO DIABETES CARE
LA English
DT Article
ID GLYCEMIC CONTROL; COMPLICATIONS TRIAL; CHILDREN; YOUTH; CARBOHYDRATE;
ADOLESCENTS; BEHAVIORS; MELLITUS; THERAPY; OBESITY
AB OBJECTIVE-The purpose of this study was to develop a survey of general and diabetes-specific nutrition knowledge for youth with type 1 diabetes and their parents and to assess the survey's psychometric properties.
RESEARCH DESIGN AND METHODS-A multidisciplinary pediatric team developed the Nutrition Knowledge Survey (NKS) and administered it to youth with type I diabetes (n = 282,49% females, 13.3 +/- 2.9 years) and their parents (82% mothers). The NKS content domains included healthful eating, carbohydrate counting, blood glucose response to foods, and nutrition label reading. Higher NKS scores reflect greater nutrition knowledge (score range is 0-100%). In youths, glycemic control was assessed by A1C, and dietary quality was determined by the Healthy Eating Index-2005 (HEI-2005) derived from 3-day diet records. Validity was based on associations of NKS scores with A1C and dietary quality. Reliability was assessed using the Kuder-Richardson Formula 20 (KR-20) and correlations of domain scores to total score.
RESULTS-Mean NKS scores (23 items) were 56.9 +/- 16.4% for youth and 73.4 +/- 12.5% for parents. The KR-20 was 0.70 for youth and 0.59 for parents, representing acceptable internal consistency of the measure. In multivariate analysis, controlling for youth age, family income, parent education, diabetes duration, and insulin regimen, parent NKS scores were associated with corresponding youth A1C (beta = -0.13, P = 0.03). Both parent (beta = 0.20, P = 0.002) and youth (beta = 0.25, P < 0.001) NKS scores were positively associated with youth HEI-2005 scores.
CONCLUSIONS-The NKS appears to be a useful measure of general and diabetes-specific nutrition knowledge for youth with type 1 diabetes and their parents.
C1 [Rovner, Alisha J.; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.
[Mehta, Sanjeev N.; Higgins, Laurie A.; Laffel, Lori M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02115 USA.
RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.
EM nanselt@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HH-SN-267200703434C]
FX This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (Contract HH-SN-267200703434C).
NR 20
TC 4
Z9 4
U1 0
U2 17
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2012
VL 35
IS 8
BP 1643
EP 1647
DI 10.2337/dc11-2371
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 980KD
UT WOS:000306891200004
PM 22665217
ER
PT J
AU Volpato, S
Bianchi, L
Lauretani, F
Lauretani, F
Bandinelli, S
Guralnik, JM
Zuliani, G
Ferrucci, L
AF Volpato, Stefano
Bianchi, Lara
Lauretani, Fulvio
Lauretani, Fabrizio
Bandinelli, Stefania
Guralnik, Jack M.
Zuliani, Giovanni
Ferrucci, Luigi
TI Role of Muscle Mass and Muscle Quality in the Association Between
Diabetes and Gait Speed
SO DIABETES CARE
LA English
DT Article
ID PHYSICAL PERFORMANCE BATTERY; PERIPHERAL ARTERIAL-DISEASE;
LOWER-EXTREMITY DISABILITY; BODY-COMPOSITION; OLDER-ADULTS; SUBSEQUENT
DISABILITY; GLUCOSE-TOLERANCE; SKELETAL-MUSCLE; WOMENS HEALTH; INCHIANTI
AB OBJECTIVE-Older people with type 2 diabetes are at high risk of mobility disability. We investigated the association of diabetes with lower-limb muscle mass and muscle quality to verify whether diabetes-related muscle impairments mediate the association between diabetes and low walking speed.
RESEARCH DESIGN AND METHODS-We performed a cross-sectional analysis of 835 participants (65 years old and older) enrolled in the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) population-based study. Total, muscular, and fat cross-sectional areas of the calf and relative muscle density were measured using peripheral quantitative computerized tomography. Indicators of muscle performance included knee-extension torque, ankle plantar flexion and dorsiflexion strength, lower-extremity muscle power, and ankle muscle quality (ratio of ankle strength to the muscle area [kilograms per centimeters squared]). Gait performance was assessed by 4- and 400-m walking speed. Diabetes was ascertained by standard American Diabetes Association criteria.
RESULTS-Prevalence of diabetes was 11.4%. After adjustment for age and sex, participants with diabetes had lower muscle density, knee and ankle strength, and muscle power and worse muscle quality (all P < 0.05). Diabetic participants were also slower on both 4-m (beta: -0.115 +/- 0.024 oils, P < 0.001) and 400-m (beta: 0.053 +/- 0.023 m/s, P < 0.05) walking tests. In multivariable linear regression models, lower-limb muscle characteristics accounted for 24.3 and 15.1% of walking speed difference comparing diabetic and nondiabetic subjects in the 4- and 400-m walks, respectively.
CONCLUSIONS-In older persons, diabetes is associated with reduced muscle strength and worse muscle quality. These impairments are important contributors of walking limitations related to diabetes.
C1 [Volpato, Stefano; Bianchi, Lara; Zuliani, Giovanni] Univ Ferrara, Sect Internal Med & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Dept Geriatr Rehabil, Parma, Italy.
[Lauretani, Fabrizio] Tuscany Reg Hlth Agcy, Florence, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Volpato, S (reprint author), Univ Ferrara, Sect Internal Med & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
EM vlt@unife.it
RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016
OI VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani,
Fulvio/0000-0002-5287-9972
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336]
FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted
project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the U.S. National Institute on Aging (263 MD 9164 and 263 MD
821336).
NR 33
TC 53
Z9 54
U1 5
U2 14
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2012
VL 35
IS 8
BP 1672
EP 1679
DI 10.2337/dc11-2202
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 980KD
UT WOS:000306891200009
PM 22596176
ER
PT J
AU Djousse, L
Khawaja, O
Bartz, TM
Biggs, ML
Ix, JH
Zieman, SJ
Kizer, JR
Tracy, RP
Siscovick, DS
Mukamal, KJ
AF Djousse, Luc
Khawaja, Owais
Bartz, Traci M.
Biggs, Mary L.
Ix, Joachim H.
Zieman, Susan J.
Kizer, Jorge R.
Tracy, Russell P.
Siscovick, David S.
Mukamal, Kenneth J.
TI Plasma Fatty Add-Binding Protein 4, Nonesterified Fatty Acids, and
Incident Diabetes in Older Adults
SO DIABETES CARE
LA English
DT Article
ID DE-NOVO LIPOGENESIS; METABOLIC SYNDROME; ADIPOSE-TISSUE; CARDIOVASCULAR
HEALTH; INSULIN; OBESITY; HUMANS; RISK; ATHEROSCLEROSIS; BIOMARKER
AB OBJECTIVE-To examine the relation of fatty acid binding protein (FABP)4 and nonesterified fatty acids (NEFAs) to diabetes in older adults.
RESEARCH DESIGN AND METHODS-We ascertained incident diabetes among 3,740 Cardiovascular Health Study participants (1992-2007) based on the use of hypoglycemic medications, fasting glucose >= 126 mg/dL, or nonfasting glucose >= 200 mg/cIL. FABP4 and NEFA were measured on specimens collected between 1992 and 1993.
RESULTS-Mean age of the 3,740 subjects studied was 74.8 years. For each SD increase in log FABP4, hazard ratios (HRs) for diabetes were 1.35 (95% CI 1.10-1.65) for women and 1.45 (1.13-1.85) for men controlling for age, race, education, physical activity, cystatin C, alcohol intake, smoking, self-reported health status, and estrogen use for women (P for sex-FABP4 interaction 0.10). BMI modified the FABP4-diabetes relation (P = 0.009 overall; 0.02 for women and 0.135 for men), in that statistically significant higher risk of diabetes was mainly seen in men with BMI <25 kg/m(2) (HR per SD: 1.78 [95% CI 1.13-2.81]). There was a modest and nonsignificant association of NEFA with diabetes (P-trend = 0.21). However, when restricted to the first 5 years of follow-up, multivariable-adjusted HRs for diabetes were 1.0 (ref.), 1.68(95% CI 1.12-2.53), and 1.63 (1.07-2.50) across consecutive tertiles of NEFA (P-trend = 0.03).
CONCLUSIONS-Plasma FABP4 was positively associated with incident diabetes in older adults, and such association was statistically significant in lean men only. A significant positive association between plasma NEFA and incident diabetes was observed during the first 5 years of follow-up.
C1 [Djousse, Luc; Khawaja, Owais] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Djousse, Luc; Khawaja, Owais] Harvard Univ, Sch Med, Boston, MA USA.
[Djousse, Luc; Khawaja, Owais] Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Djousse, Luc; Khawaja, Owais] Boston Vet Affairs Healthcare Syst, Clin Ctr & Massachusetts Vet Epidemiol & Res Info, Boston, MA USA.
[Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Bartz, Traci M.; Biggs, Mary L.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA.
[Zieman, Susan J.] NIA, NIH, Bethesda, MD 20892 USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT USA.
[Siscovick, David S.] Univ Washington, Dept Med & Epidemiol, Cardiovascular Hlth Res Unit, Seattle, WA USA.
[Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
RP Djousse, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA.
EM ldjousse@rics.bwh.harvard.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute [R01HL094555, N01-HC-85239,
N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083,
N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL080295, R01-HL075366];
National Institute on Aging [AG-023629., R01-AG15928, R01-AG20098,
R01-HL085710-01, R01-AG027058]; National Institute of Neurological
Disorders and Stroke; University of Pittsburgh Claude D. Pepper Older
Americans Independence Center [P30-AG-024827]
FX The research reported in this article was supported by the National
Heart, Lung, and Blood Institute (R01HL094555 to L.D., J.H.I., S.J.Z.,
and J.R.K.). Additional support was provided by the National Institute
on Aging (AG-023629). The CHS was supported by contracts N01-HC-85239,
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 U01-HL080295 from
the National Heart, Lung, and Blood Institute, with additional
contribution from the National Institute of Neurological Disorders and
Stroke. Additional support was provided by grants R01-AG15928,
R01-AG20098, R01-HL085710-01, and R01-AG027058 from the National
Institute on Aging; R01-HL075366 from the National Heart, Lung, and
Blood Institute; and the University of Pittsburgh Claude D. Pepper Older
Americans Independence Center (P30-AG-024827).
NR 40
TC 5
Z9 5
U1 1
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2012
VL 35
IS 8
BP 1701
EP 1707
DI 10.2337/dc11-1690
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 980KD
UT WOS:000306891200014
PM 22584136
ER
PT J
AU Sullivan, MD
O'Connor, P
Feeney, P
Hire, D
Simmons, DL
Raisch, DW
Fine, LJ
Narayan, KMV
Ali, MK
Katon, WJ
AF Sullivan, Mark D.
O'Connor, Patrick
Feeney, Patricia
Hire, Don
Simmons, Debra L.
Raisch, Dennis W.
Fine, Lawrence J.
Narayan, K. M. Venkat
Ali, Mohammad K.
Katon, Wayne J.
TI Depression Predicts All-Cause Mortality Epidemiological evaluation from
the ACCORD HRQL substudy
SO DIABETES CARE
LA English
DT Article
ID QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION; COMORBID DEPRESSION;
METAANALYSIS; ASSOCIATION; ADULTS; RISK; CARE; PREVALENCE; SYMPTOMS
AB OBJECTIVE-Depression affects up to 20-25% of adults with type 2 diabetes and may increase all-cause mortality, but few well-designed studies have examined the effects of depression on the full range of cardiovascular disease outcomes in type 2 diabetes.
RESEARCH DESIGN AND METHODS-A total of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Health-Related Quality of Life substudy completed the Patient Health Questionnaire (PHQ)-9 measure of depression symptoms at baseline and 12, 36, and 48 months. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% CI) for the time-varying impact of depression on protocol-defined clinical outcomes with and without adjustment for demographic, trial-related, clinical, and behavioral variables.
RESULTS-In fully adjusted models, depression was not significantly related to the ACCORD primary composite outcome (cardiovascular death, nonfatal heart attack, or stroke) (HR 1.53 [95% CI 0.85-2.73]) or to the ACCORD microvascular composite outcome (0.93 [0.53-1.62]), but all-cause mortality was significantly increased both in those with PHQ-assessed probable major depression (2.24 [1.24-4.06]) and PHQ score of >= 10 (1.84 [1.17-2.89]). The effect of depression on all-cause mortality was not related to previous cardiovascular events or to assignment to intensive or standard glycemia control. Probable major depression (by PHQ-9) had a borderline impact on the ACCORD macrovascular end point (1.42 [0.99-2.04]).
CONCLUSIONS-Depression increases the risk of all-cause mortality and may increase the risk of macrovascular events among adults with type 2 diabetes at high risk for cardiovascular events.
C1 [Sullivan, Mark D.; Katon, Wayne J.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[O'Connor, Patrick] HealthPartners, Minneapolis, MN USA.
[Feeney, Patricia; Hire, Don] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Simmons, Debra L.] Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA.
[Simmons, Debra L.] John L McClellan Mem Vet Adm Med Ctr, Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[Raisch, Dennis W.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA.
[Raisch, Dennis W.] Clin Res Pharm Coordinating Ctr, Vet Affairs Cooperat Studies Program, Albuquerque, NM USA.
[Fine, Lawrence J.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Narayan, K. M. Venkat; Ali, Mohammad K.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA.
RP Sullivan, MD (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
EM sullimar@uw.edu
RI Narayan, K.M. Venkat /J-9819-2012
OI Narayan, K.M. Venkat /0000-0001-8621-5405
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of Health; National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases; National Institutes of Health, National Institute on
Aging; National Institutes of Health, National Eye Institute; Centers
for Disease Control and Prevention; General Clinical Research Centers
FX This study was supported by grants N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, and IAA-Y1-HC-1010 from the National Heart, Lung, and
Blood Institute; by other components of the National Institutes of
Health, including the National Institute of Diabetes and Digestive and
Kidney Diseases, the National Institute on Aging, and the National Eye
Institute; by the Centers for Disease Control and Prevention; and by
General Clinical Research Centers.
NR 26
TC 51
Z9 51
U1 1
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2012
VL 35
IS 8
BP 1708
EP 1715
DI 10.2337/dc11-1791
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 980KD
UT WOS:000306891200015
PM 22619083
ER
PT J
AU Chao, DM
He, XZ
Yang, YL
Bazzy-Asaad, A
Lazarus, LH
Balboni, G
Kim, DH
Xia, Y
AF Chao, Dongman
He, Xiaozhou
Yang, Yilin
Bazzy-Asaad, Alia
Lazarus, Lawrence H.
Balboni, Gianfranco
Kim, Dong H.
Xia, Ying
TI DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels
via PKC mechanisms in the cortex
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Delta-opioid receptor; Ionic homeostasis; Na+ influx; Na+ channel;
Neuroprotection; Hypoxia/ischemia
ID PROTEIN-KINASE-C; OXYGEN-GLUCOSE DEPRIVATION; OPIOID RECEPTOR
ACTIVATION; TRANSIENT FOCAL ISCHEMIA; RAT CEREBRAL-CORTEX; NULL MUTANT
MOUSE; SODIUM-CHANNELS; IN-VITRO; BRAIN EDEMA; NEURONAL EXCITABILITY
AB Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na+ influx through TTX-sensitive voltage-gated Na+ channels may be a main mechanism for hypoxia-induced disruption of K+ homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na+ channels. In the present study we examined the role of DOR in the regulation of Na+ influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na+ influx induced by a Na+ channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na+ activity in mouse cortical slices with Na+ selective electrodes and found that (1) anoxia-induced Na+ influx occurred mainly through TTX-sensitive Na+ channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na+ influx; (3) veratridine, a Na+ channel opener, enhanced the anoxia-induced Na+ influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na+ influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKC beta II peptide inhibitor, and PKC theta pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na+ influx through Na+ channels via PKC (especially PKC beta II and PKC theta isoforms) dependent mechanisms in the cortex. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Xia, Ying] Univ Texas Med Sch Houston, Vivian L Smith Dept Neurosurg, Houston, TX 77030 USA.
[Chao, Dongman; He, Xiaozhou; Yang, Yilin] Soochow Univ, Med Coll 3, Changzhou 213003, Jiangsu, Peoples R China.
[Chao, Dongman; Bazzy-Asaad, Alia; Xia, Ying] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
[Balboni, Gianfranco] Univ Cagliari, I-09124 Cagliari, Italy.
RP Xia, Y (reprint author), Univ Texas Med Sch Houston, Vivian L Smith Dept Neurosurg, 6431 Fannin St,MSE R421, Houston, TX 77030 USA.
EM Ying.Xia@uth.tmc.edu
FU National Institutes of Health [HD-034852, AT-004422]; Vivian L Smith
Neurological Foundation; Division of Intramural Research of NIEHS; CSB
[CS20092015]; CHB [ZD200903]; NSFC [31071046]
FX This work was supported by grants from the National Institutes of Health
(HD-034852 and AT-004422) and the Vivian L Smith Neurological
Foundation. LHL was supported by the Division of Intramural Research of
NIEHS and NIH. XH and YY were supported by CSB (CS20092015), CHB
(ZD200903) and NSFC (31071046).
NR 69
TC 15
Z9 16
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD AUG
PY 2012
VL 236
IS 2
BP 228
EP 239
DI 10.1016/j.expneurol.2012.05.006
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 976YI
UT WOS:000306622900004
PM 22609332
ER
PT J
AU Ng, TB
Cheung, RCF
Ye, XJ
Fang, EF
Chan, YS
Pan, WL
Dan, XL
Yin, CM
Lam, SK
Lin, P
Ngai, PHK
Xia, LX
Liu, F
Ye, XY
Wang, HX
Wong, JH
AF Ng, Tzi Bun
Cheung, Randy Chi Fai
Ye, Xiu Juan
Fang, Evandro Fei
Chan, Yau Sang
Pan, Wen Liang
Dan, Xiu Li
Yin, Cui Ming
Lam, Sze Kwan
Lin, Peng
Ngai, Patrick Hung Kui
Xia, Li Xin
Liu, Fang
Ye, Xiu Yun
Wang, He Xiang
Wong, Jack Ho
TI Pharmacotherapy approaches to antifungal prophylaxis
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE amphotericin; antifungal prophylaxis; azoles; cost-effectiveness; drug
therapy; echinocandins
ID INVASIVE FUNGAL-INFECTIONS; STEM-CELL TRANSPLANTATION; ACUTE
MYELOID-LEUKEMIA; OF-THE-LITERATURE; POSACONAZOLE PROPHYLAXIS;
FLUCONAZOLE PROPHYLAXIS; CANDIDA-ALBICANS; HEMATOLOGICAL MALIGNANCIES;
LUNG TRANSPLANTATION; AMPHOTERICIN-B
AB Introduction: Invasive fungal infection (IFI) is a serious problem due to difficulties in early diagnosis and high mortality. Different approaches are adopted for the treatment and management of IFI, including prophylactic, empiric, preemptive and directed strategies.
Areas covered: This paper reviews the type of pharmacotherapy used for antifungal prophylaxis in infants with extremely low birth weights, pediatric patients with cardiac disease, preterm neonates, pediatric oncology patients, adult cancer patients with neutropenia, adult patients with hematologic malignancy, hematopoietic stem-cell transplantation recipients, organ transplant recipients, HIV-infected patients, immunosuppressed patients treated with moderate or high doses of corticosteroids, and patients with invasive fusariosis, candidemia, invasive candidiasis, systemic mycoses and immunocompromised patients.
Expert opinion: Azole drugs are the drugs most often used in cost-effective antifungal prophylaxis of patients with conditions such as immunodeficiency and cancer, which render them highly susceptible to IFI. Fluconazole is the most outstanding example. However, there are many azoles with different pharmacological characteristics that the physician can choose from. Echinocandins have favorable characteristics that make them useful for treating Candida infections. Antibodies, or their engineered derivatives directed against cell-wall polysaccharides and glycopeptides, and some protein epitopes of Candida albicans, appear to be a promising novel approach for prophylaxis against Candida infection and deserve further in-depth investigations.
C1 [Ng, Tzi Bun; Cheung, Randy Chi Fai; Chan, Yau Sang; Pan, Wen Liang; Dan, Xiu Li; Yin, Cui Ming; Wong, Jack Ho] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Ye, Xiu Juan] Fujian Agr & Forestry Univ, Minist Educ, Key Lab Biopesticide & Chem Biol, Fuzhou 350002, Fujian, Peoples R China.
[Ng, Tzi Bun; Wong, Jack Ho] Agr & Forestry Univ, Inst Plant Virol, Fujian Prov Key Lab Plant Virol, Fuzhou, Fujian, Peoples R China.
[Ye, Xiu Juan] Fujian Agr & Forestry Univ, Inst Plant Virol, Key Lab Plant Virol Fujian Prov, Fuzhou 350002, Fujian, Peoples R China.
[Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA.
[Wang, He Xiang] China Agr Univ, Dept Microbiol, State Key Lab Agrobiotechnol, Beijing 100094, Peoples R China.
[Ye, Xiu Yun] Fuzhou Univ, Coll Biol Sci & Technol, Fuzhou 350002, Peoples R China.
[Ye, Xiu Yun] Fuzhou Univ, Natl Engn Lab High Efficiency Enzyme Express, Fuzhou 350002, Peoples R China.
[Lam, Sze Kwan] Univ Hong Kong, Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Liu, Fang] Nankai Univ, Coll Life Sci, Dept Microbiol, Tianjin 300071, Peoples R China.
[Xia, Li Xin] Shenzhen Univ, Sch Med, Dept Basic Med Sci, Shenzhen, Guangdong, Peoples R China.
[Ngai, Patrick Hung Kui] Chinese Univ Hong Kong, Fac Sci, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.
[Lin, Peng] Novartis, Shanghai, Peoples R China.
RP Ng, TB (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
EM b021770@mailserv.cuhk.edu.hk; xiujuanye2004@gmail.com;
jack1993@yahoo.com
FU Food and Health Bureau, the Government of Hong Kong Special
Administrative Region [10090812]
FX The authors declare no conflict of interest. The award of a research
grant (Research Funds for the Control of Infectious Diseases, project
reference no. 10090812) by Food and Health Bureau, the Government of
Hong Kong Special Administrative Region, is gratefully acknowledged.
NR 73
TC 3
Z9 4
U1 1
U2 19
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD AUG
PY 2012
VL 13
IS 12
BP 1695
EP 1705
DI 10.1517/14656566.2012.698263
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 975PZ
UT WOS:000306524600004
PM 22716311
ER
PT J
AU Fan, JG
Dong, LJ
Mishra, S
Chen, YW
FitzGerald, P
Wistow, G
AF Fan, Jianguo
Dong, Lijin
Mishra, Sanghamitra
Chen, Yingwei
FitzGerald, Paul
Wistow, Graeme
TI A role for gamma S-crystallin in the organization of actin and fiber
cell maturation in the mouse lens
SO FEBS JOURNAL
LA English
DT Article
DE actin cytoskeleton; crystallins; knock-out mouse; organelles
ID SEQUENCE TAG ANALYSIS; HEAT-SHOCK PROTEINS; EYE LENS; ALPHA-CRYSTALLIN;
MACULAR DEGENERATION; VERTEBRATE LENS; NONLENS MEMBER; BOVINE LENS;
CATARACT; DIFFERENTIATION
AB ?S-crystallin (?S) is a highly conserved component of the eye lens. To gain insights into the functional role(s) of this protein, the mouse gene (Crygs) was deleted. Although mutations in ?S can cause severe cataracts, loss of function of ?S in knockout (KO) mice produced no obvious lens opacity, but was associated with focusing defects. Electron microscopy showed no major differences in lens cell organization, suggesting that the optical defects are primarily cytoplasmic in origin. KO lenses were also grossly normal by light microscopy but showed evidence of incomplete clearance of cellular organelles in maturing fiber cells. Phalloidin labeling showed an unusual distribution of F-actin in a band of mature fiber cells in KO lenses, suggesting a defect in the organization or processing of the actin cytoskeleton. Indeed, in wild-type lenses, ?S and F-actin colocalize along the fiber cell plasma membrane. Relative levels of F-actin and G-actin in wild-type and KO lenses were estimated from fluorescent staining profiles and from isolation of actin fractions from whole lenses. Both methods showed a two-fold reduction in the F-actin/G-actin ratio in KO lenses, whereas no difference in tubulin organization was detected. In vitro experiments showed that recombinant mouse ?S can directly stabilize F-actin. This suggests that ?S may have a functional role related to actin, perhaps in shepherding filaments to maintain the optical properties of the lens cytoplasm and normal fiber cell maturation.
C1 [Fan, Jianguo; Dong, Lijin; Mishra, Sanghamitra; Chen, Yingwei; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
[FitzGerald, Paul] Univ Calif Davis, Sch Med, Dept Cell Biol & Human Anat, Davis, CA 95616 USA.
RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct Genom, NIH, Bg 6,Rm 106, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
FU Intramural Program of the National Eye Institute; NEI Core Grant [P30
EY12576, EY08747]
FX This work was supported by the Intramural Program of the National Eye
Institute and by NEI Core Grant P30 EY12576, UC Davis, and EY08747 to P.
FitzGerald.
NR 64
TC 7
Z9 7
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD AUG
PY 2012
VL 279
IS 16
BP 2892
EP 2904
DI 10.1111/j.1742-4658.2012.08669.x
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 978JB
UT WOS:000306735500008
PM 22715935
ER
PT J
AU Levy, G
Hill, MJ
Ramirez, CI
Correa, L
Ryan, ME
DeCherney, AH
Levens, ED
Whitcomb, BW
AF Levy, Gary
Hill, Micah J.
Ramirez, Christina I.
Correa, Luiz
Ryan, Mary E.
DeCherney, Alan H.
Levens, Eric D.
Whitcomb, Brian W.
TI The use of follicle flushing during oocyte retrieval in assisted
reproductive technologies: a systematic review and meta-analysis
SO HUMAN REPRODUCTION
LA English
DT Review
DE follicle flushing; oocyte retrieval; in-vitro fertilization; assisted
reproductive technologies
ID FERTILIZATION PROGRAM; INVITRO FERTILIZATION; CONTROLLED-TRIALS;
RANDOMIZED-TRIAL; ASPIRATION; RECOVERY; STIMULATION; QUALITY; NEEDLES;
IVF
AB Does follicular flushing during assisted reproductive technologies (ART) improve the number of oocytes retrieved?
Follicular flushing during ART does not result in a greater number of oocytes in normal responders.
Despite limited evidence supporting the use of follicular flushing, it continues to be a common procedure in many ART clinics. Prior studies have provided conflicting results regarding the routine use of flushing during oocyte retrieval.
Systematic review and meta-analysis of 518 patients who participated in 6 randomized trials over 20 years.
Literature searches were conducted to retrieve randomized controlled trials on follicle or ovarian flushing in ART. Databases searched included PubMed, EMBASE, Web of Science and the Cochrane Database of Clinical Trials (CENTRAL). Six trials that included 518 subjects matched the inclusion criteria. Studies included were limited to trials that were published, randomized trials comparing oocyte retrieval with a single-lumen pick-up needle versus follicle flushing after direct aspiration with a multi-channel oocyte pick-up needle in ART patients.
In each of the trials, measures of the oocyte yield (oocytes retrieved divided by follicles aspirated), total oocytes retrieved, fertilization or pregnancy were not different when comparing direct aspiration with follicle flushing. Four trials reported a higher operative time with follicle flushing. Results of the meta-analysis indicated no significant differences in the oocytes retrieved [weighted mean difference: 0.07, 95 confidence interval (CI): 0.13 to 0.29] or the oocyte yield (odds ratio: 1.06, 95 CI: 0.951.18) between the non-flushing and flushing groups.
All trials featured an open label design and the majority of patients in this meta-analysis were normal responders. The applications of these results to poor responders, patients undergoing natural cycle ART or minimal stimulation ART should be made with caution.
Follicle flushing does not improve ART outcomes in normal-responding patients and should not be performed. This meta-analysis should solidify this recommendation as it includes the largest trial published on the subject and is consistent with a recently published Cochrane review.
This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD. The authors have no competing interests to declare.
N/A.
C1 [Whitcomb, Brian W.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA.
[Levy, Gary; Hill, Micah J.; Ramirez, Christina I.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Correa, Luiz] Tripler Army Med Ctr, Honolulu, HI 96859 USA.
[Ryan, Mary E.] Natl Inst Hlth Lib, Bethesda, MD USA.
[Levens, Eric D.] Shady Grove Fertil Ctr, Bethesda, MD USA.
RP Whitcomb, BW (reprint author), Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, 408 Arnold House,715 N Pleasant St, Amherst, MA 01003 USA.
EM bwhitcomb@schoolph.umass.edu
FU NICHD, NIH, Bethesda, MD
FX This work was supported, in part, by the Program in Reproductive and
Adult Endocrinology, NICHD, NIH, Bethesda, MD.
NR 24
TC 10
Z9 10
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD AUG
PY 2012
VL 27
IS 8
BP 2373
EP 2379
DI 10.1093/humrep/des174
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 977HZ
UT WOS:000306648600015
PM 22647450
ER
PT J
AU Kroeger, DR
Rudulier, CD
Peters, NC
Bretscher, PA
AF Kroeger, David R.
Rudulier, Christopher D.
Peters, Nathan C.
Bretscher, Peter A.
TI Direct demonstration of CD4 T cell cooperation in the primary in vivo
generation of CD4 effector T cells
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE OX40; OX40L; T helper cells; T-T cooperation; vaccination
ID OX40 LIGAND; B-CELLS; COSTIMULATORY MOLECULE; ANTIGEN; IMMUNITY;
ACTIVATION; EXPRESSION; LYMPHOCYTES; INDUCTION; RECEPTOR
AB Many observations bear upon the cellular and molecular requirements for CD4 T cell activation. The interaction of CD4 T cells with dendritic cells (DC), central to the induction of most immune responses, is the most studied. However, leukocytes other than DC can dramatically affect the induction and differentiation of CD4 T cells into effector cells. We recently provided indirect evidence that in vivo CD4 T cooperation facilitates the activation of CD4 T cells. Here, we demonstrate that the activation of CD4 T cells, specific for the hen egg lysozyme (HEL)(105-120) peptide, is optimally achieved when BALB/c mice are immunized with additional MHC class II-binding HEL peptides in incomplete Freund's adjuvant. This cooperation cannot be mimicked by the coadministration of LPS or of an agonistic antibody to CD40, at the time of immunization. In contrast, OX40-OX40L interactions are necessary for CD4 T cell cooperation in that an OX40 agonistic antibody can replace, and an OX40L-blocking antibody can abrogate, CD4 T cell cooperation in situations where such cooperation would otherwise enhance the activation of CD4 T cells.
C1 [Kroeger, David R.; Rudulier, Christopher D.; Bretscher, Peter A.] Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada.
[Peters, Nathan C.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bretscher, PA (reprint author), Univ Saskatchewan, Dept Microbiol & Immunol, A305-107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada.
EM peter.bretscher@usask.ca
FU Natural Sciences and Engineering Research Council of Canada
[327335-2008]
FX Natural Sciences and Engineering Research Council of Canada
(327335-2008).
NR 36
TC 4
Z9 4
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD AUG
PY 2012
VL 24
IS 8
BP 519
EP 527
DI 10.1093/intimm/dxs055
PG 9
WC Immunology
SC Immunology
GA 981LE
UT WOS:000306968900005
PM 22527289
ER
PT J
AU Kung, LHW
Rajpar, MH
Preziosi, R
Briggs, MD
Boot-Handford, RP
AF Kung, L. H. W.
Rajpar, M. H.
Preziosi, R.
Briggs, M. D.
Boot-Handford, R. P.
TI Investigating the role of endoplasmic reticulum stress in
chondrodysplasias
SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
LA English
DT Meeting Abstract
CT Autumn Meeting of the British-Society-for-Matrix-Biology (BSMB)
CY SEP 08-09, 2011
CL Univ Newcastle, Newcastle, ENGLAND
SP British Soc Matrix Biol (BSMB)
HO Univ Newcastle
C1 [Kung, L. H. W.; Briggs, M. D.; Boot-Handford, R. P.] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England.
[Rajpar, M. H.; Preziosi, R.] NICHD, NIH, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA.
[Rajpar, M. H.; Preziosi, R.] Univ Manchester, Evolut Res Grp, Fac Life Sci, Manchester M13 9PT, Lancs, England.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0959-9673
J9 INT J EXP PATHOL
JI Int. J. Exp. Pathol.
PD AUG
PY 2012
VL 93
IS 4
BP A17
EP A18
PG 2
WC Pathology
SC Pathology
GA 975MX
UT WOS:000306516500026
ER
PT J
AU Santesso, N
Schunemann, H
Blumenthal, P
De Vuyst, H
Gage, J
Garcia, F
Jeronimo, J
Lu, R
Luciani, S
Quek, SC
Awad, T
Broutet, N
AF Santesso, Nancy
Schuenemann, Holger
Blumenthal, Paul
De Vuyst, Hugo
Gage, Julia
Garcia, Francisco
Jeronimo, Jose
Lu, Ricky
Luciani, Silvana
Quek, Swee C.
Awad, Tahany
Broutet, Nathalie
CA World Health Org Steering Comm
TI World Health Organization Guidelines: Use of cryotherapy for cervical
intraepithelial neoplasia
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Editorial Material
DE Cervical cancer; Cervical intraepithelial neoplasia; Cryotherapy;
Guidelines; Loop electrosurgical excision procedure; Recommendations
AB Background: In 2008, cervical cancer was responsible for 275 000 deaths, of which approximately 88% occurred in low-and middle-income countries. In 2009, the World Health Organization (WHO) committed to updating recommendations for use of cryotherapy for cervical intraepithelial neoplasia (CIN). Methods and results: We followed the WHO Handbook for Guidelines Development to develop present guidelines. An expert panel was established, which included clinicians, researchers, program directors, and methodologists. An independent group conducted systematic reviews and produced evidence summaries following the GRADE approach. GRADE evidence profiles were created for 16 key questions about the effects of cryotherapy in the presence of histologically confirmed CIN compared with no treatment and with loop electrosurgical excision procedure, as well as the use of different cryotherapy techniques. We identified a small number of randomized controlled trials or independently controlled observational studies. Surrogate outcomes were reported when evidence about outcomes critical to decision making were not available. The panel made 14 recommendations and documented factors that determined the strength and direction of the recommendations in decision tables. Conclusion: The present document summarizes new evidence-based WHO recommendations about the use of cryotherapy in women with histologically confirmed CIN for low-, middle-, and high-income countries. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Schuenemann, Holger] McMaster Univ, Dept Clin Epidemiol & Biostat, Hlth Sci Ctr, Hamilton, ON L8S 4K1, Canada.
[Blumenthal, Paul] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[De Vuyst, Hugo] IARC, Lyon, France.
[Gage, Julia] NCI, Washington, DC USA.
[Garcia, Francisco] Amer Canc Soc, Tucson, AZ USA.
[Jeronimo, Jose] PATH, Seattle, WA USA.
[Lu, Ricky] Jhpiego, Baltimore, MD USA.
[Luciani, Silvana] WHO Reg Off Amer, Washington, DC USA.
[Quek, Swee C.] KK Womens & Childrens Hosp, Singapore, Singapore.
[Broutet, Nathalie] World Hlth Org, Geneva, Switzerland.
RP Schunemann, H (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, Hlth Sci Ctr, Room 2C16,1280 Main St W, Hamilton, ON L8S 4K1, Canada.
EM schuneh@mcmaster.ca
NR 7
TC 17
Z9 18
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD AUG
PY 2012
VL 118
IS 2
BP 97
EP 102
DI 10.1016/j.ijgo.2012.01.029
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 977BB
UT WOS:000306630200003
PM 22727415
ER
PT J
AU Wang, Z
Chen, F
Ward, M
Bhattacharyya, T
AF Wang, Zhong
Chen, Foster
Ward, Michael
Bhattacharyya, Timothy
TI Compliance with Surgical Care Improvement Project Measures and
Hospital-Associated Infections Following Hip Arthroplasty
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID MOLECULAR-WEIGHT HEPARIN; KNEE ARTHROPLASTY; VENOUS THROMBOEMBOLISM;
UNITED-STATES; SITE INFECTION; PROPHYLAXIS; PREVENTION; OUTCOMES;
SURGERY; RISK
AB Background: Hospital compliance with the Surgical Care Improvement Project (SCIP) measures has increased recently for patients undergoing hip arthroplasty. However, reductions in postoperative infections were less than expected, and concern remains about complications associated with prophylaxis against venous thromboembolism (VTE). We sought to examine the association between hospital adherence to SCIP measures and postoperative infections.
Methods: We conducted an observational study of 17,714 patients who underwent hip replacement in 2008 at 128 New York state hospitals. These hospitals were divided into less compliant and highly compliant groups, on the basis of their levels of compliance compared with the median value of compliance with SCIP measures. From the New York State Department of Health annual report, we collected the confirmed postoperative infections at the facility level. From the Healthcare Cost and Utilization Project state inpatient database, we identified incidences of postoperative infections at the patient level, using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes.
Results: During 2008, mean hospital compliance increased from 93.5% to 96.0% for the infection prevention measure and from 91.4% to 97.5% for the VTE prevention measure. Higher adherence to infection prevention measures was not associated with a significant reduction in infection (p >= 0.09 for all). Hospitals that were at least 97% compliant with the SCIP VTE-2 measure (patients receiving VTE prophylaxis around the time of surgery) reported significantly higher infection rates compared with less compliant hospitals (1.60% versus 0.93%; p < 0.001). Similarly, patients from highly compliant hospitals (for the VTE-2 measure) were at significant risk of postoperative infection (adjusted odds ratio, 1.50; 95% confidence interval, 1.07 to 2.12; p = 0.02).
Conclusions: Targeting complete compliance with SCIP infection prevention measures was not associated with additional reductions in infection outcomes following hip replacement. Furthermore, significant risk of postoperative infections may result from increased perioperative use of VTE prophylactics.
C1 [Wang, Zhong; Chen, Foster; Ward, Michael; Bhattacharyya, Timothy] NIAMSD, Clin Trials & Outcomes Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Wang, Z (reprint author), CTOB IRP NIAMS NIH, Bldg 10 CRC,Room 4-1350,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
EM john.wang@nih.gov
NR 27
TC 15
Z9 17
U1 2
U2 4
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD AUG 1
PY 2012
VL 94A
IS 15
BP 1359
EP 1366
DI 10.2106/JBJS.K.00911
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 981AZ
UT WOS:000306939000003
PM 22740029
ER
PT J
AU Newth, CJL
Meert, KL
Clark, AE
Moler, FW
Zuppa, AF
Berg, RA
Pollack, MM
Sward, KA
Berger, JT
Wessel, DL
Harrison, RE
Reardon, J
Carcillo, JA
Shanley, TP
Holubkov, R
Dean, JM
Doctor, A
Nicholson, CE
AF Newth, Christopher J. L.
Meert, Kathleen L.
Clark, Amy E.
Moler, Frank W.
Zuppa, Athena F.
Berg, Robert A.
Pollack, Murray M.
Sward, Katherine A.
Berger, John T.
Wessel, David L.
Harrison, Rick E.
Reardon, Jean
Carcillo, Joseph A.
Shanley, Thomas P.
Holubkov, Richard
Dean, J. Michael
Doctor, Allan
Nicholson, Carol E.
CA Eunice Kennedy Shriver Natl Inst
TI Fatal and Near-Fatal Asthma in Children: The Critical Care Perspective
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID DRIVEN ALBUTEROL NEBULIZATION; RANDOMIZED CONTROLLED-TRIAL;
PLACEBO-CONTROLLED TRIAL; MECHANICAL VENTILATION; INTRAVENOUS
SALBUTAMOL; PEDIATRIC ASTHMA; INTENSIVE-CARE; EARLY MANAGEMENT; DISTINCT
ENTITY; DEATHS
AB Objective To characterize the clinical course, therapies, and outcomes of children with fatal and near-fatal asthma admitted to pediatric intensive care units (PICUs).
Study design This was a retrospective chart abstraction across the 8 tertiary care PICUs of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Inclusion criteria were children (aged 1-18 years) admitted between 2005 and 2009 (inclusive) for asthma who received ventilation (near-fatal) or died (fatal). Data collected included medications, ventilator strategies, concomitant therapies, demographic information, and risk variables.
Results Of the 261 eligible children, 33 (13%) had no previous history of asthma, 218 (84%) survived with no known complications, and 32 (12%) had complications. Eleven (4%) died, 10 of whom had experienced cardiac arrest before admission. Patients intubated outside the PICU had a shorter duration of ventilation (median, 25 hours vs 84 hours; P < .001). African-Americans were disproportionately represented among the intubated children and had a shorter duration of intubation. Barotrauma occurred in 15 children (6%) before admission. Pharmacologic therapy was highly variable, with similar outcomes.
Conclusion Of the children ventilated in the CPCCRN PICUs, 96% survived to hospital discharge. Most of the children who died experienced cardiac arrest before admission. Intubation outside the PICU was correlated with shorter duration of ventilation. Complications of barotrauma and neuromyopathy were uncommon. Practice patterns varied widely among the CPCCRN sites. (J Pediatr 2012;161:214-21).
C1 [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, Los Angeles, CA 90027 USA.
[Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Clark, Amy E.; Holubkov, Richard; Dean, J. Michael] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Moler, Frank W.; Shanley, Thomas P.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Zuppa, Athena F.; Berg, Robert A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Pollack, Murray M.] Phoenix Childrens Hosp, Dept Pediat, Phoenix, AZ USA.
[Sward, Katherine A.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Sward, Katherine A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
[Berger, John T.; Wessel, David L.; Reardon, Jean] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Harrison, Rick E.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Carcillo, Joseph A.] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA.
[Doctor, Allan] Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63130 USA.
[Nicholson, Carol E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Bethesda, MD USA.
RP Newth, CJL (reprint author), Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, 4650 Sunset Blvd, Los Angeles, CA 90027 USA.
EM cnewth@chla.usc.edu
OI Doctor, Allan/0000-0002-6096-6400
FU Eunice Kennedy Shriver National Institute for Child Health and Human
Development [U10-HD050012, U10-HD050096, U10-HD063108, U10-HD049983,
U10-HD049981, U10-HD063114, U10-HD063106]; Obstetric and Pediatric
Pharmacology Branch; Best Pharmaceuticals for Children Act
FX Supported by the Eunice Kennedy Shriver National Institute for Child
Health and Human Development (cooperative agreements U10-HD050012,
U10-HD050096, U10-HD063108, U10-HD049983, U10-HD049981, U10-HD063114,
and U10-HD063106), the Obstetric and Pediatric Pharmacology Branch, and
the Best Pharmaceuticals for Children Act. The authors declare no
conflicts of interest.
NR 44
TC 16
Z9 17
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD AUG
PY 2012
VL 161
IS 2
BP 214
EP +
DI 10.1016/j.jpeds.2012.02.041
PG 11
WC Pediatrics
SC Pediatrics
GA 977VV
UT WOS:000306693800012
PM 22494876
ER
PT J
AU Vohr, BR
Stephens, BE
Higgins, RD
Bann, CM
Hintz, SR
Das, A
Newman, JE
Peralta-Carcelen, M
Yolton, K
Dusick, AM
Evans, PW
Goldstein, RF
Ehrenkranz, RA
Pappas, A
Adams-Chapman, I
Wilson-Costello, DE
Bauer, CR
Bodnar, A
Heyne, RJ
Vaucher, YE
Dillard, RG
Acarregui, MJ
McGowan, EC
Myers, GJ
Fuller, J
AF Vohr, Betty R.
Stephens, Bonnie E.
Higgins, Rosemary D.
Bann, Carla M.
Hintz, Susan R.
Das, Abhik
Newman, Jamie E.
Peralta-Carcelen, Myriam
Yolton, Kimberly
Dusick, Anna M.
Evans, Patricia W.
Goldstein, Ricki F.
Ehrenkranz, Richard A.
Pappas, Athina
Adams-Chapman, Ira
Wilson-Costello, Deanne E.
Bauer, Charles R.
Bodnar, Anna
Heyne, Roy J.
Vaucher, Yvonne E.
Dillard, Robert G.
Acarregui, Michael J.
McGowan, Elisabeth C.
Myers, Gary J.
Fuller, Janell
CA Eunice Kennedy Shriver Natl Inst
TI Are Outcomes of Extremely Preterm Infants Improving? Impact of Bayley
Assessment on Outcomes
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LOW-BIRTH-WEIGHT; NEONATAL INTENSIVE-CARE; NEURODEVELOPMENTAL OUTCOMES;
CEREBRAL-PALSY; CHILDREN BORN; SCHOOL-AGE; PREVALENCE; HEMORRHAGE
AB Objectives To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development's Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2).
Study design Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates.
Results Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score < 70 and < 85, cognitive or language score < 70; cognitive or motor score < 70, and cognitive, language, or motor score < 70 (P < .001).
Conclusion Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution. (J Pediatr 2012;161:222-8).
C1 [Vohr, Betty R.; Stephens, Bonnie E.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02905 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Bann, Carla M.; Newman, Jamie E.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Peralta-Carcelen, Myriam] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Yolton, Kimberly] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Dusick, Anna M.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Evans, Patricia W.] Univ Texas Houston, Med Sch Houston, Dept Pediat, Houston, TX USA.
[Goldstein, Ricki F.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Pappas, Athina] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Adams-Chapman, Ira] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Adams-Chapman, Ira] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Wilson-Costello, Deanne E.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Bauer, Charles R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Bodnar, Anna] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Heyne, Roy J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Vaucher, Yvonne E.] Univ Calif San Diego, Div Neonatol, La Jolla, CA 92093 USA.
[Dillard, Robert G.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Acarregui, Michael J.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[McGowan, Elisabeth C.] Floating Hosp Children, Dept Pediat, Div Newborn Med, Tufts Med Ctr, Boston, MA USA.
[Myers, Gary J.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Fuller, Janell] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Vohr, BR (reprint author), Brown Univ, Women & Infants Hosp, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM bvohr@wihri.org
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX Supported by grants from the National Institutes of Health and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. Data collected at participating sites of the National
Institute of Child Health and Human Development's Neonatal Research
Network were transmitted to RTI International, the data coordinating
center for the network, which stored, managed, and analyzed the data for
this study. The authors declare no conflicts of interest.
NR 27
TC 65
Z9 68
U1 2
U2 19
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD AUG
PY 2012
VL 161
IS 2
BP 222
EP +
DI 10.1016/j.jpeds.2012.01.057
PG 10
WC Pediatrics
SC Pediatrics
GA 977VV
UT WOS:000306693800013
PM 22421261
ER
PT J
AU Greenberg, RG
Benjamin, DK
Gantz, MG
Cotten, CM
Stoll, BJ
Walsh, MC
Sanchez, PJ
Shankaran, S
Das, A
Higgins, RD
Miller, NA
Auten, KJ
Walsh, TJ
Laptook, AR
Carlo, WA
Kennedy, KA
Finer, NN
Duara, S
Schibler, K
Ehrenkranz, RA
Van Meurs, KP
Frantz, ID
Phelps, DL
Poindexter, BB
Bell, EF
O'Shea, TM
Watterberg, KL
Goldberg, RN
Smith, PB
AF Greenberg, Rachel G.
Benjamin, Daniel K., Jr.
Gantz, Marie G.
Cotten, C. Michael
Stoll, Barbara J.
Walsh, Michele C.
Sanchez, Pablo J.
Shankaran, Seetha
Das, Abhik
Higgins, Rosemary D.
Miller, Nancy A.
Auten, Kathy J.
Walsh, Thomas J.
Laptook, Abbot R.
Carlo, Waldemar A.
Kennedy, Kathleen A.
Finer, Neil N.
Duara, Shahnaz
Schibler, Kurt
Ehrenkranz, Richard A.
Van Meurs, Krisa P.
Frantz, Ivan D., III
Phelps, Dale L.
Poindexter, Brenda B.
Bell, Edward F.
O'Shea, T. Michael
Watterberg, Kristi L.
Goldberg, Ronald N.
Smith, P. Brian
CA Eunice Kennedy Shriver Natl Inst
TI Empiric Antifungal Therapy and Outcomes in Extremely Low Birth Weight
Infants with Invasive Candidiasis
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID INTENSIVE-CARE-UNIT; LATE-ONSET SEPSIS; NEONATAL CANDIDIASIS; FUNGAL
COLONIZATION; CANCER-PATIENTS; BLOOD CULTURES; RISK-FACTORS; INFECTION;
GUIDELINES; MORTALITY
AB Objective To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants.
Study design This was a cohort study of infants with a birth weight <= 1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
Results A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes.
Conclusion Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted. (J Pediatr 2012;161:264-9).
C1 [Greenberg, Rachel G.; Benjamin, Daniel K., Jr.; Cotten, C. Michael; Auten, Kathy J.; Goldberg, Ronald N.; Smith, P. Brian] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Gantz, Marie G.] Res Triangle Inst Int, Stat Res Unit, Res Triangle Pk, NC USA.
[Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Sanchez, Pablo J.; Miller, Nancy A.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Das, Abhik] Res Triangle Inst Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Kennedy, Kathleen A.] Univ Texas Houston, Dept Pediat, Med Sch Houston, Houston, TX USA.
[Finer, Neil N.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Schibler, Kurt] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Frantz, Ivan D., III] Tufts Med Ctr, Dept Pediat, Boston, MA USA.
[Phelps, Dale L.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[O'Shea, T. Michael] Wake Forest Univ, Dept Pediat, Winston Salem, NC 27109 USA.
[Watterberg, Kristi L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Greenberg, RG (reprint author), Duke Univ, Dept Pediat, Durham, NC 27706 USA.
RI Smith, Phillip/I-5565-2014;
OI Greenberg, Rachel/0000-0003-4156-8543
FU FDA HHS [R01 FD003519]; NCATS NIH HHS [UL1 TR000041, UL1 TR000454];
NICHD NIH HHS [K23 HD044799-02, HHSN267200700051C, K23 HD044799, K23
HD060040, K23 HD060040-04, K24 HD058735, L40 HD069892, L40 HD069892-04,
R01 HD057956, U10 HD021373, U10 HD027856, U10 HD040461, U10 HD045962,
U10 HD053089]
NR 36
TC 16
Z9 20
U1 1
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD AUG
PY 2012
VL 161
IS 2
BP 264
EP +
DI 10.1016/j.jpeds.2012.01.053
PG 8
WC Pediatrics
SC Pediatrics
GA 977VV
UT WOS:000306693800020
PM 22424952
ER
PT J
AU Lateef, TM
Cui, LH
Nelson, KB
Nakamura, EF
Merikangas, KR
AF Lateef, Tarannum M.
Cui, Lihong
Nelson, Karin B.
Nakamura, Erin F.
Merikangas, Kathleen R.
TI Physical Comorbidity of Migraine and Other Headaches in US Adolescents
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID SUPPLEMENT NCS-A; EPILEPSY; PREVALENCE; ASSOCIATION; DIFFICULTIES;
DISORDERS; CHILDREN; SEIZURES; DESIGN; BURDEN
AB Objective To examine the pattern and extent to which other physical conditions are comorbid with migraine and other headaches in youth in a representative sample of the US population.
Study design The National Comorbidity Survey-Adolescent Supplement is a face-to-face survey of adolescents aged 13-18 years in the continental US. Sufficient information to assess the International Headache Society's criteria for migraine with and without aura over the past 12 months was available in the diagnostic module. A caretaker/parental self-administered report was used to assess a broad range of other physical conditions. The sample for these analyses was 6843 adolescents with systematic caretaker/parent reports.
Results Adolescents with any headaches reported higher rates of other neurologic conditions, including epilepsy (OR, 2.02; 95% CI, 1.04-3.94), persistent nightmares (OR, 2.28; 95% CI, 1.34-3.87), and motion sickness (OR, 1.6; 95% CI, 1.07-2.4), as well as abdominal complaints (OR, 2.36; 95% CI, 1.59-3.51). Asthma (OR, 2.22; 95% CI, 1.26-3.92) and seasonal allergies (OR, 1.66; 95% CI, 1.12-2.48) were more common in adolescents with migraines than in adolescents with nonspecific headaches.
Conclusion Adolescent migraine is associated with inflammatory conditions such as asthma and seasonal allergies, as well as with epilepsy, persistent nightmares, and motion sickness. Our findings suggest that comorbid medical conditions should be evaluated comprehensively in determining treatment options in youth with headache. Such comorbidity also could be an important source of the clinical and etiologic heterogeneity in migraine. (J Pediatr 2012;161:308-13).
C1 [Lateef, Tarannum M.] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, Washington, DC 20010 USA.
[Lateef, Tarannum M.; Nelson, Karin B.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Lateef, Tarannum M.; Cui, Lihong; Nakamura, Erin F.; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Nelson, Karin B.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Nelson, Karin B.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA.
RP Lateef, TM (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, Washington, DC 20010 USA.
EM TLateef@cnmc.org
FU National Institute of Mental Health [Z01 MH002808-08, U01-MH60220];
National Comorbidity Survey Adolescent Supplement (NCS-A)
FX Supported by the Intramural Research Program of the National Institute
of Mental Health (grant Z01 MH002808-08), the National Comorbidity
Survey Adolescent Supplement (NCS-A), and the National Institute of
Mental Health (grant U01-MH60220).
NR 48
TC 11
Z9 11
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD AUG
PY 2012
VL 161
IS 2
BP 308
EP +
DI 10.1016/j.jpeds.2012.01.040
PG 7
WC Pediatrics
SC Pediatrics
GA 977VV
UT WOS:000306693800030
PM 22381023
ER
PT J
AU Weinfurt, K
Flynn, K
Lim, L
Bruner, D
Dombeck, C
Cyranowski, J
Jeffery, D
Keefe, F
Luecht, R
Porter, L
Reese, J
Reeve, B
Smith, A
Willse, J
AF Weinfurt, K.
Flynn, K.
Lim, L.
Bruner, D.
Dombeck, C.
Cyranowski, J.
Jeffery, D.
Keefe, F.
Luecht, R.
Porter, L.
Reese, J.
Reeve, B.
Smith, A.
Willse, J.
TI DEVELOPMENT AND VALIDATION OF THE PROMIS SEXUAL FUNCTION MEASURE
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Meeting Abstract
C1 [Weinfurt, K.; Flynn, K.; Lim, L.; Dombeck, C.; Keefe, F.; Porter, L.] Duke Univ, Durham, NC 27706 USA.
[Bruner, D.] Emory Univ, Atlanta, GA 30322 USA.
[Cyranowski, J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Luecht, R.; Willse, J.] Univ N Carolina, Greensboro, NC 27412 USA.
[Reeve, B.] Univ N Carolina, Chapel Hill, NC USA.
[Smith, A.] NCI, Bethesda, MD 20892 USA.
RI Flynn, Kathryn/M-5346-2013
OI Flynn, Kathryn/0000-0002-4427-3583
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
J9 J SEX MED
JI J. Sex. Med.
PD AUG
PY 2012
VL 9
SU 4
SI SI
MA 071
BP 208
EP 208
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 982NZ
UT WOS:000307053600070
ER
PT J
AU Weinfurt, K
Flynn, K
Moore, A
Lim, L
Bruner, D
Reese, J
Smith, A
Reeve, B
AF Weinfurt, K.
Flynn, K.
Moore, A.
Lim, L.
Bruner, D.
Reese, J.
Smith, A.
Reeve, B.
TI REASONS FOR SEXUAL INACTIVITY: RESULTS FROM A NATIONAL SURVEY
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Meeting Abstract
C1 [Weinfurt, K.; Flynn, K.; Moore, A.; Lim, L.] Duke Univ, Durham, NC 27706 USA.
[Bruner, D.] Emory Univ, Atlanta, GA 30322 USA.
[Smith, A.] NCI, Bethesda, MD 20892 USA.
[Reeve, B.] Univ N Carolina, Chapel Hill, NC USA.
RI Flynn, Kathryn/M-5346-2013
OI Flynn, Kathryn/0000-0002-4427-3583
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
J9 J SEX MED
JI J. Sex. Med.
PD AUG
PY 2012
VL 9
SU 4
SI SI
MA 072
BP 209
EP 209
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 982NZ
UT WOS:000307053600071
ER
PT J
AU Flynn, K
Reese, J
Bruner, D
Dombeck, C
Keefe, F
Czajkowski, S
Reeve, B
Shelby, R
Weinfurt, K
AF Flynn, K.
Reese, J.
Bruner, D.
Dombeck, C.
Keefe, F.
Czajkowski, S.
Reeve, B.
Shelby, R.
Weinfurt, K.
TI PATIENTS' UNDERSTANDING OF INTEREST, DESIRE, AND AROUSAL
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Meeting Abstract
C1 [Flynn, K.; Dombeck, C.; Keefe, F.; Shelby, R.; Weinfurt, K.] Duke Univ, Durham, NC 27706 USA.
[Reese, J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Bruner, D.] Emory Univ, Atlanta, GA 30322 USA.
[Czajkowski, S.] NHLBI, Bethesda, MD USA.
[Reeve, B.] Univ N Carolina, Chapel Hill, NC USA.
RI Flynn, Kathryn/M-5346-2013
OI Flynn, Kathryn/0000-0002-4427-3583
NR 0
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
J9 J SEX MED
JI J. Sex. Med.
PD AUG
PY 2012
VL 9
SU 4
SI SI
MA 120
BP 225
EP 225
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 982NZ
UT WOS:000307053600117
ER
PT J
AU Colan, SD
Shirali, G
Margossian, R
Gallagher, D
Altmann, K
Canter, C
Chen, S
Golding, F
Radojewski, E
Camitta, M
Carboni, M
Rychik, J
Stylianou, M
Tani, LY
Tierney, ESS
Wang, YL
Sleeper, LA
AF Colan, Steven D.
Shirali, Girish
Margossian, Renee
Gallagher, Dianne
Altmann, Karen
Canter, Charles
Chen, Shan
Golding, Fraser
Radojewski, Elizabeth
Camitta, Michael
Carboni, Michael
Rychik, Jack
Stylianou, Mario
Tani, Lloyd Y.
Tierney, Elif Seda Selamet
Wang, Yanli
Sleeper, Lynn A.
CA Pediat Heart Network Investigators
TI The Ventricular Volume Variability Study of the Pediatric Heart Network:
Study Design and Impact of Beat Averaging and Variable Type on the
Reproducibility of Echocardiographic Measurements in Children with
Chronic Dilated Cardiomyopathy
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Cardiomyopathy; Ventricular function; Pediatrics; Echocardiography;
Reproducibility
ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; SURROGATE END-POINTS; FAILURE; TRIALS;
RESPIRATION; ALGORITHM; INFANTS; AREA
AB Background: Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.
Methods: Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 x difference/mean).
Results: Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error.
Conclusions: This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible. (J Am Soc Echocardiogr 2012;25:842-54.)
C1 [Colan, Steven D.] Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA.
[Colan, Steven D.; Margossian, Renee; Tierney, Elif Seda Selamet] Harvard Univ, Sch Med, Boston, MA USA.
[Colan, Steven D.; Gallagher, Dianne; Chen, Shan; Wang, Yanli; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA.
[Shirali, Girish] Med Univ S Carolina, Charleston, SC 29425 USA.
[Altmann, Karen] Columbia Univ, Med Ctr, New York, NY USA.
[Camitta, Michael; Carboni, Michael] Duke Univ, Med Ctr, Durham, NC USA.
[Canter, Charles] St Louis Childrens Hosp, St Louis, MO 63178 USA.
[Golding, Fraser; Radojewski, Elizabeth] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Rychik, Jack] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA.
[Tani, Lloyd Y.] Univ Utah, Salt Lake City, UT USA.
RP Colan, SD (reprint author), Childrens Hosp Boston, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM colan@alum.mit.edu
OI Carboni, Michael/0000-0002-9875-7276
FU National Heart, Lung, and Blood Institute [U01, HL068269, HL068270,
HL068279, HL068281, HL068285, HL068292, HL068290, HL068288]
FX From the Children's Hospital Boston and Harvard Medical School, Boston,
Massachusetts (S.D.C., R.M., E.S.S.T.); New England Research Institutes,
Watertown, Massachusetts (S.D.C., D.G., S.C., Y.W., L.A.S.); the Medical
University of South Carolina, Charleston, South Carolina (G.S.);
Columbia University Medical Center, New York, New York (K.A.); Duke
University Medical Center, Durham, North Carolina (M.Camitta,
M.Carboni); St. Louis Children's Hospital, St. Louis, Missouri (C.C.);
The Hospital for Sick Children, Toronto, Ontario, Canada (F.G., E.R.);
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
(J.R.); the National Heart, Lung, and Blood Institute, Bethesda,
Maryland (M.S.); and the University of Utah, Salt Lake City, Utah
(L.Y.T.). Drs. Colan and Shirali are joint first authors of this work.
This study was supported by U01 grants from the National Heart, Lung,
and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285,
HL068292, HL068290, and HL068288). The contents of this publication are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Heart, Lung, and Blood
Institute. This study's ClinicalTrials.gov identifier is NCT00123071.
NR 23
TC 33
Z9 33
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD AUG
PY 2012
VL 25
IS 8
BP 842
EP +
DI 10.1016/j.echo.2012.05.004
PG 19
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 977KJ
UT WOS:000306657900008
PM 22677278
ER
PT J
AU Flatz, L
Cheng, C
Wang, LS
Foulds, KE
Ko, SY
Kong, WP
Roychoudhuri, R
Shi, W
Bao, S
Todd, JP
Asmal, M
Shen, L
Donaldson, M
Schmidt, SD
Gall, JGD
Pinschewer, DD
Letvin, NL
Rao, S
Mascola, JR
Roederer, M
Nabel, GJ
AF Flatz, Lukas
Cheng, Cheng
Wang, Lingshu
Foulds, Kathryn E.
Ko, Sung-Youl
Kong, Wing-Pui
Roychoudhuri, Rahul
Shi, Wei
Bao, Saran
Todd, John-Paul
Asmal, Mohammed
Shen, Ling
Donaldson, Mitzi
Schmidt, Stephen D.
Gall, Jason G. D.
Pinschewer, Daniel D.
Letvin, Norman L.
Rao, Srinivas
Mascola, John R.
Roederer, Mario
Nabel, Gary J.
TI Gene-Based Vaccination with a Mismatched Envelope Protects against
Simian Immunodeficiency Virus Infection in Nonhuman Primates
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; T-CELL RESPONSES; NEUTRALIZING
ANTIBODIES; RHESUS-MONKEYS; ADENOVIRAL VECTOR; DENDRITIC CELLS; EFFICACY
TRIAL; HIV-1 VACCINE; IMMUNOGENICITY; IMMUNITY
AB The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanisms of preventive AIDS vaccines remains a priority, and nonhuman primate (NHP) models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mismatched SIV envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239, prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with efficacies of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent Sly infection in NHPs and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials.
C1 [Flatz, Lukas; Cheng, Cheng; Wang, Lingshu; Foulds, Kathryn E.; Ko, Sung-Youl; Kong, Wing-Pui; Roychoudhuri, Rahul; Shi, Wei; Bao, Saran; Todd, John-Paul; Donaldson, Mitzi; Schmidt, Stephen D.; Letvin, Norman L.; Rao, Srinivas; Mascola, John R.; Roederer, Mario; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Asmal, Mohammed; Shen, Ling; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02115 USA.
[Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD USA.
[Pinschewer, Daniel D.] Univ Geneva, WHO Collaborating Ctr Vaccinol & Neonatal Immunol, Dept Pathol & Immunol, Geneva, Switzerland.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
RI Schmidt, Stephen/B-5398-2012; Roychoudhuri, Rahul/A-7442-2010
OI Roychoudhuri, Rahul/0000-0002-5392-1853
FU Intramural Research Program of the Vaccine Research Center; NIAID;
National Institutes of Health; Mayenfisch Foundation
FX This research was supported in part by the Intramural Research Program
of the Vaccine Research Center, NIAID, National Institutes of Health.
L.F. was supported by the Mayenfisch Foundation.
NR 46
TC 22
Z9 23
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 AUG
PY 2012
VL 86
IS 15
BP 7760
EP 7770
DI 10.1128/JVI.00599-12
PG 11
WC Virology
SC Virology
GA 976VE
UT WOS:000306614400004
PM 22593152
ER
PT J
AU Gomez-Blanco, J
Luque, D
Gonzalez, JM
Carrascosa, JL
Alfonso, C
Trus, B
Havens, WM
Ghabrial, SA
Caston, JR
AF Gomez-Blanco, Josue
Luque, Daniel
Gonzalez, Jose M.
Carrascosa, Jose L.
Alfonso, Carlos
Trus, Benes
Havens, Wendy M.
Ghabrial, Said A.
Caston, Jose R.
TI Cryphonectria nitschkei Virus 1 Structure Shows that the Capsid Protein
of Chrysoviruses Is a Duplicated Helix-Rich Fold Conserved in Fungal
Double-Stranded RNA Viruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PENICILLIUM-CHRYSOGENUM-VIRUS; MOLECULAR SWITCH; REVEALS
AB Cryoelectron microscopy reconstruction of Cryphonectria nitschkei virus 1, a double-stranded RNA (dsRNA) virus, shows that the capsid protein (60 copies/particle) is formed by a repeated helical core, indicative of gene duplication. This unusual organization is common to chrysoviruses. The arrangement of many of these putative alpha-helices is conserved in the totivirus L-A capsid protein, suggesting a shared motif. Our results indicate that a 120-,subunit T=1 capsid is a conserved architecture that optimizes dsRNA replication and organization.
C1 [Gomez-Blanco, Josue; Luque, Daniel; Gonzalez, Jose M.; Carrascosa, Jose L.; Caston, Jose R.] CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Madrid, Spain.
[Gomez-Blanco, Josue] Ctr Estudios Avanzados Cuba CEAC CITMA, Havana, Cuba.
[Alfonso, Carlos] CSIC, Ctr Invest Biol, Madrid, Spain.
[Trus, Benes] NIH, Imaging Sci Lab, CIT, Bethesda, MD 20892 USA.
[Havens, Wendy M.; Ghabrial, Said A.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA.
RP Caston, JR (reprint author), CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Campus Cantoblanco, Madrid, Spain.
EM jrcaston@cnb.csic.es
RI Caston, Jose/L-5896-2014; Alfonso, Carlos/K-1316-2014; Luque,
Daniel/I-6467-2015;
OI Caston, Jose/0000-0003-2350-9048; Alfonso, Carlos/0000-0001-7165-4800;
Luque, Daniel/0000-0002-0151-6020; Gonzalez, Jose M/0000-0001-5569-0705
FU Spanish Ministry of Science and Innovation [BFU2011-25902,
BFU2011-29038]; NIH Intramural Research Program; Center for Information
Technology; Kentucky Science & Engineering Foundation
FX This work was supported by grants from the Spanish Ministry of Science
and Innovation (BFU2011-25902 to J.R.C. and BFU2011-29038 to J.L.C.),
the NIH Intramural Research Program with support from the Center for
Information Technology (to B.T.), and the Kentucky Science & Engineering
Foundation (to S.A.G.).
NR 17
TC 9
Z9 9
U1 0
U2 7
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 AUG
PY 2012
VL 86
IS 15
BP 8314
EP 8318
DI 10.1128/JVI.00802-12
PG 5
WC Virology
SC Virology
GA 976VE
UT WOS:000306614400054
PM 22593169
ER
PT J
AU Doria-Rose, NA
Georgiev, I
O'Dell, S
Chuang, GY
Staupe, RP
McLellan, JS
Gorman, J
Pancera, M
Bonsignori, M
Haynes, BF
Burton, DR
Koff, WC
Kwong, PD
Mascola, JR
AF Doria-Rose, Nicole A.
Georgiev, Ivelin
O'Dell, Sijy
Chuang, Gwo-Yu
Staupe, Ryan P.
McLellan, Jason S.
Gorman, Jason
Pancera, Marie
Bonsignori, Mattia
Haynes, Barton F.
Burton, Dennis R.
Koff, Wayne C.
Kwong, Peter D.
Mascola, John R.
TI A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant
of Resistance to V1/V2 Neutralizing Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; ENV CLONES; PG16; PG9; BROAD; INFECTIONS;
COVERAGE; REVEAL; TARGET
AB Antibody PG9 is a prototypical member of a class of V1/V2-directed antibodies that effectively neutralizes diverse strains of HIV-1. We analyzed strain-specific resistance to PG9 using sequence and structural information. For multiply resistant strains, mutations in a short segment of V1/V2 resulted in gain of sensitivity to PG9 and related V1/V2 neutralizing antibodies, suggesting both a common mechanism of HIV-1 resistance to and a common mode of recognition by this class of antibodies.
C1 [Doria-Rose, Nicole A.; Georgiev, Ivelin; O'Dell, Sijy; Chuang, Gwo-Yu; Staupe, Ryan P.; McLellan, Jason S.; Gorman, Jason; Pancera, Marie; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC USA.
[Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA.
[Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pkwong@mail.nih.gov; jmascola@mail.nih.gov
FU Intramural Research Program of the Vaccine Research Center, NIAID, NIH;
Center for HIV/AIDS Vaccine Immunology (CHAVI) grant from the Division
of AIDS, NIAID, NIH [AI067854]; NIAID, NIH [AI 033292]; International
AIDS Vaccine Initiative
FX Support for this work was provided by the Intramural Research Program of
the Vaccine Research Center, NIAID, NIH, by the Center for HIV/AIDS
Vaccine Immunology (CHAVI) grant AI067854 from the Division of AIDS,
NIAID, NIH, by grant AI 033292 from NIAID, NIH, and by the International
AIDS Vaccine Initiative.
NR 17
TC 40
Z9 40
U1 0
U2 7
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 AUG
PY 2012
VL 86
IS 15
BP 8319
EP 8323
DI 10.1128/JVI.00696-12
PG 5
WC Virology
SC Virology
GA 976VE
UT WOS:000306614400055
PM 22623764
ER
PT J
AU Csiszar, A
Sosnowska, D
Wang, MY
Lakatta, EG
Sonntag, WE
Ungvari, Z
AF Csiszar, Anna
Sosnowska, Danuta
Wang, Mingyi
Lakatta, Edward G.
Sonntag, William E.
Ungvari, Zoltan
TI Age-Associated Proinflammatory Secretory Phenotype in Vascular Smooth
Muscle Cells From the Non-human Primate Macaca mulatta: Reversal by
Resveratrol Treatment
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Vascular aging; Inflammation; Oxidative stress; Cytokine-3,5,4
'-trihydroxy-trans-stilbene
ID NF-KAPPA-B; ARTERIAL ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; LEWIS
DWARF RATS; OXIDATIVE STRESS; LIFE-SPAN; TRANSCRIPTION FACTOR; CALORIC
RESTRICTION; DNA-DAMAGE; TNF-ALPHA
AB There is increasing evidence that age-associated chronic low-grade inflammation promotes the development of both large-vessel disease (myocardial infarction, stroke, peripheral arterial disease) and small-vessel pathologies (including vascular cognitive impairment) in older persons. However, the source of age-related chronic vascular inflammation remains unclear. To test the hypothesis that cell-autonomous mechanisms contribute to the proinflammatory changes in vascular phenotype that accompanies advancing age, we analyzed the cytokine secretion profile of primary vascular smooth muscle cells (VSMCs) derived from young (similar to 13 years old) and aged (similar to 21 years old) Macaca mulatto. Aged VSMCs cultured in the absence of systemic factors exhibited significantly increased secretion of interleukin-1 beta, MCP-1, and tumor necrosis factor alpha compared with young control cells. Secretion of interleukin-6 also tended to increase in aged VSMCs. This age-associated proinflammatory shift in the cellular secretory phenotype was associated with an increased mitochondrial O-2(-) production and nuclear factor kappa-light-chain-enhancer of activated B cells activation. Treatment of aged VSMCs with a physiologically relevant concentration of resveratrol (1 mu M) exerted significant anti-inflammatory effects, reversing aging-induced alterations in the cellular cytokine secretion profile and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells. Resveratrol also attenuated mitochondrial O-2(-) production and upregulated the transcriptional activity of Nrf2 in aged VSMCs. Thus, in non-human primates, cell-autonomous activation of nuclear factor kappa-light-chain-enhancer of activated B cells and expression of an inflammatory secretome likely contribute to vascular inflammation in aging. Resveratrol treatment prevents the proinflammatory properties of the aged VSMC secretome, an effect that likely contributes to the demonstrated vasoprotective action of resveratrol in animal models of aging.
C1 [Csiszar, Anna; Sosnowska, Danuta; Sonntag, William E.; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Wang, Mingyi; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Ungvari, Z (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM anna-csiszar@ouhsc.edu; zoltan-ungvari@ouhsc.edu
FU American Diabetes Association; American Federation for Aging Research;
Oklahoma Center for the Advancement of Science and Technology;
University of Oklahoma College of Medicine Alumni Association; American
Heart Association; National Institutes of Health [AG031085, AT006526,
AG038747, NS056218, P01 AG11370]; Ellison Medical Foundation; Donald W.
Reynolds Foundation
FX American Diabetes Association to Z.U.; American Federation for Aging
Research to A.C.; Oklahoma Center for the Advancement of Science and
Technology to A.C. and Z.U.; University of Oklahoma College of Medicine
Alumni Association to A.C.; American Heart Association to A.C.; National
Institutes of Health (AG031085 to A.C.: AT006526 to Z.U.; AG038747,
NS056218, and P01 AG11370 to W.E.S.); The Ellison Medical Foundation to
W.E.S.; Intramural Research Program of National Institutes of Health to
E.L. and M.W.; The authors would like to express their gratitude for the
support of the Donald W. Reynolds Foundation, which funds aging research
at the University of Oklahoma Health Sciences Center under its Aging and
Quality of Life Program.
NR 84
TC 47
Z9 50
U1 2
U2 16
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 AUG
PY 2012
VL 67
IS 8
BP 811
EP 820
DI 10.1093/gerona/glr228
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 977CE
UT WOS:000306633200001
PM 22219513
ER
PT J
AU Valcarcel-Ares, MN
Gautam, T
Warrington, JP
Bailey-Downs, L
Sosnowska, D
de Cabo, R
Losonczy, G
Sonntag, WE
Ungvari, Z
Csiszar, A
AF Noa Valcarcel-Ares, M.
Gautam, Tripti
Warrington, Junie P.
Bailey-Downs, Lora
Sosnowska, Danuta
de Cabo, Rafael
Losonczy, Gyorgy
Sonntag, William E.
Ungvari, Zoltan
Csiszar, Anna
TI Disruption of Nrf2 Signaling Impairs Angiogenic Capacity of Endothelial
Cells: Implications for Microvascular Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Vascular aging; Microcirculation; Capillary density; Angiogenesis; Heart
ID OXIDATIVE STRESS RESISTANCE; GROWTH-FACTOR EXPRESSION; NADPH OXIDASE
ACTIVITY; LIFE-SPAN; GENE-EXPRESSION; CARDIOVASCULAR-DISEASE; OXIDIZED
PHOSPHOLIPIDS; ANTIOXIDANT GENES; ANGINA-PECTORIS; DOUBLE-BLIND
AB The redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2) plays a key role in preserving a healthy endothelial phenotype and maintaining the functional integrity of the vasculature. Previous studies demonstrated that aging is associated with Nrf2 dysfunction in endothelial cells, which alters redox signaling and likely promotes the development of large vessel disease. Much less is known about the consequences of Nrf2 dysfunction at the level of the microcirculation. To test the hypothesis that Nrf2 regulates angiogenic capacity of endothelial cells, we determined whether disruption of Nrf2 signaling (by siRNA knockdown of Nrf2 and overexpression of Keap1, the cytosolic repressor of Nrf2) impairs angiogenic processes in cultured human coronary arterial endothelial cells stimulated with vascular endothelial growth factor and insulin-like growth factor-1. In the absence of functional Nrf2, coronary arterial endothelial cells exhibited impaired proliferation and adhesion to vitronectin and collagen. Disruption of Nrf2 signaling also reduced cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology) and impaired the ability of coronary arterial endothelial cells to form capillary-like structures. Collectively, we find that Nrf2 is essential for normal endothelial angiogenic processes, suggesting that Nrf2 dysfunction may be a potential mechanism underlying impaired angiogenesis and microvascular rarefaction in aging.
C1 [Noa Valcarcel-Ares, M.; Gautam, Tripti; Warrington, Junie P.; Bailey-Downs, Lora; Sosnowska, Danuta; Sonntag, William E.; Ungvari, Zoltan; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Oklahoma City, OK 73104 USA.
[Noa Valcarcel-Ares, M.] CHU, Biol Inst Invest Biomed A Coruna INIBIC, Aging & Inflammat Res Lab, La Coruna, Spain.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Losonczy, Gyorgy] Semmelweis Univ, Dept Pulmonol, H-1085 Budapest, Hungary.
RP Csiszar, A (reprint author), Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM zoltan-ungvari@ouhsc.edu; anna-csiszar@ouhsc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Warrington,
Junie/0000-0001-5626-8872; , rafael/0000-0003-2830-5693
FU American Diabetes Association; American Federation for Aging Research;
Oklahoma Center for the Advancement of Science and Technology;
University of Oklahoma College of Medicine Alumni Association; American
Heart Association; National Institutes of Health [AG031085, AT006526,
AG038747, NS056218, P01 AG11370]; Donald W. Reynolds Foundation
FX This work was supported by grants from the American Diabetes Association
(to Z.U.), American Federation for Aging Research (to A.C.), the
Oklahoma Center for the Advancement of Science and Technology (to A.C.
and Z.U.), the University of Oklahoma College of Medicine Alumni
Association (to A.C.), the American Heart Association (A.C.), the
National Institutes of Health (AG031085 to A.C., AT006526 to Z.U.,
AG038747, NS056218, and P01 AG11370 to W.E.S.), and the Intramural
Research Program of National Institutes of Health (to R.D.C.).; The
authors would like to express their gratitude for the support of the
Donald W. Reynolds Foundation, which funds aging research at the
University of Oklahoma Health Sciences Center under its Aging and
Quality of Life Program.
NR 83
TC 44
Z9 45
U1 2
U2 11
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 AUG
PY 2012
VL 67
IS 8
BP 821
EP 829
DI 10.1093/gerona/glr229
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 977CE
UT WOS:000306633200002
PM 22219515
ER
PT J
AU Taylor, CL
Albanese, E
Stewart, R
AF Taylor, Clare L.
Albanese, Emiliano
Stewart, Robert
TI The Association of Dementia With Upper Arm and Waist Circumference in
Seven Low- and Middle-Income Countries: The 10/66 Cross-Sectional
Surveys
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Dementia; Waist circumference; Arm circumference
ID BODY-MASS INDEX; ALZHEIMERS-DISEASE; INCIDENT DEMENTIA; OLDER-ADULTS;
WEIGHT-LOSS; LATE-LIFE; ADIPOSITY; POPULATION; SARCOPENIA; COMMUNITY
AB Background. Weight loss in dementia contributes to morbidity and mortality but the distribution of anthropometric change and its consistency between populations are less clear. Our aim was to investigate and compare the associations of dementia with waist and upper arm circumference in elders from seven low- and middle-income nations.
Methods. Cross-sectional surveys were conducted of 15,022 residents aged 65 years and older in Cuba, Mexico, Venezuela, Peru, Dominican Republic, China, and India. Dementia was assessed using a cross-culturally validated algorithm, and anthropometric measurements were taken. Associations with dementia and dementia severity (clinical dementia rating scale) were investigated in linear regression models, with fixed-effects meta-analyses used to investigate between-country heterogeneity.
Results. Dementia and increased dementia severity were both associated with smaller arm and waist circumferences with little evidence of confounding by sociodemographic and health status. Associations between dementia/clinical dementia rating and arm circumference were homogeneous between countries (Higgins I-2 0% and 7%, respectively), whereas those with waist circumference were more heterogeneous (Higgins I-2 67% and 62%, respectively).
Conclusions. Although cross-sectional, our findings are consistent with prospective observations of weight loss in dementia and suggest loss of both muscle and fat the former being consistent across different settings and the latter being more context dependent.
C1 [Taylor, Clare L.] Kings Coll London, Inst Psychiat, Epidemiol Sect, Dept Hlth Serv & Populat Res, London SE5 8AF, England.
[Albanese, Emiliano] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Taylor, CL (reprint author), Kings Coll London, Inst Psychiat, Epidemiol Sect, Dept Hlth Serv & Populat Res, Box 60,Crespigny Pk, London SE5 8AF, England.
EM clare.l.taylor@kcl.ac.uk
OI Stewart, Robert/0000-0002-4435-6397
FU Wellcome Trust [GR066133]
NR 37
TC 7
Z9 7
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD AUG
PY 2012
VL 67
IS 8
BP 897
EP 904
DI 10.1093/gerona/glr244
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 977CE
UT WOS:000306633200010
PM 22389465
ER
PT J
AU Fairhurst, RM
Bess, CD
Krause, MA
AF Fairhurst, Rick M.
Bess, Cameron D.
Krause, Michael A.
TI Abnormal PfEMP1/knob display on Plasmodium falciparum-infected
erythrocytes containing hemoglobin variants: fresh insights into malaria
pathogenesis and protection
SO MICROBES AND INFECTION
LA English
DT Article
DE Malaria; Plasmodium falciparum; PfEMP1; Cytoadherence; Hemoglobinopathy;
Pathogenesis
ID SICKLE-CELL TRAIT; CEREBRAL MALARIA; ENDOTHELIAL ACTIVATION; ANTIGENIC
VARIATION; ACQUIRED-IMMUNITY; FETAL-HEMOGLOBIN; BETA-THALASSEMIA;
RED-CELLS; VAR GENES; MECHANISM
AB Hemoglobin (Hb) variants are associated with reduced risk of life-threatening Plasmodium falciparum malaria syndromes, including cerebral malaria and severe malarial anemia. Despite decades of research, the mechanisms by which common Hb variants - sickle HbS, HbC, alpha-thalassemia, fetal HbF - protect African children against severe and fatal malaria have not been fully elucidated. In vitro experimental and epidemiological data have long suggested that Hb variants do not confer malaria protection by restricting the growth of parasites in red blood cells (RBCs). Recently, four Hb variants were found to impair cytoadherence, the binding of P falciparum-infected RBCs (PfRBCs) to microvascular endothelial cells (MVECs), a centrally important event in both parasite survival and malaria pathogenesis in humans. Impaired cytoadherence is associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), the parasite's major cytoadherence ligand and virulence factor, on the surface of host RBCs. We propose a model in which Hb variants allow parasites to display relatively low levels of PfEMP1, sufficient for sequestering PfRBCs in microvessels and avoiding their clearance from the bloodstream by the spleen. By preventing the display of high levels of PfEMP1, Hb variants may weaken the binding of PfRBCs to MVECs, compromising their ability to activate endothelium and initiate the downstream microvascular events that drive the pathogenesis of malaria. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Fairhurst, Rick M.; Bess, Cameron D.; Krause, Michael A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA.
EM rfairhurst@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 69
TC 29
Z9 29
U1 0
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD AUG
PY 2012
VL 14
IS 10
SI SI
BP 851
EP 862
DI 10.1016/j.micinf.2012.05.006
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 978SK
UT WOS:000306765900009
PM 22634344
ER
PT J
AU Gramza, A
Kebebew, E
AF Gramza, Ann
Kebebew, Electron
TI CANCER Thyroid cancer bone metastases and high morbidity rates
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Editorial Material
ID CARCINOMA; PREDICTORS
AB Skeletal-related events (SREs) are important measures of morbidity and mortality in patients with solid tumour bone metastases. The high rate of SREs in patients with differentiated thyroid cancer bone metastases reported by Farooki et al. indicates that routine use of antiresorptive therapy in these patients could result in reduced SREs.
C1 [Gramza, Ann; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM electron.kebebew@nih.gov
NR 9
TC 2
Z9 2
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD AUG
PY 2012
VL 8
IS 8
BP 454
EP 455
DI 10.1038/nrendo.2012.112
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 977HJ
UT WOS:000306647000004
PM 22751346
ER
PT J
AU Foster-Schubert, KE
Alfano, CM
Duggan, CR
Xiao, LR
Campbell, KL
Kong, A
Bain, CE
Wang, CY
Blackburn, GL
McTiernan, A
AF Foster-Schubert, Karen E.
Alfano, Catherine M.
Duggan, Catherine R.
Xiao, Liren
Campbell, Kristin L.
Kong, Angela
Bain, Carolyn E.
Wang, Ching-Yun
Blackburn, George L.
McTiernan, Anne
TI Effect of Diet and Exercise, Alone or Combined, on Weight and Body
Composition in Overweight-to-Obese Postmenopausal Women
SO OBESITY
LA English
DT Article
ID LIFE-STYLE INTERVENTION; DIABETES-PREVENTION-PROGRAM; RANDOMIZED
CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; LONG-TERM;
PHYSICAL-ACTIVITIES; FAT; ADULTS; MASS; SUCCESS
AB Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet toward whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of >= 10%, and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week. Participants were predominantly non-Hispanic whites (85%) with a mean age of 58.0 +/- 5.0 years, a mean BMI of 30.9 +/- 4.0 kg/m(2) and an average of 47.8 +/- 4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants' intervention assignment. Three hundred and ninety nine women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was -8.5% for the D group (P < 0.0001 vs. C), -2.4% for the E group (P = 0.03 vs. C), and -10.8% for the D+E group (P < 0.0001 vs. C), whereas the C group experienced a nonsignificant -0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle-change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.
C1 [Foster-Schubert, Karen E.; Duggan, Catherine R.; Xiao, Liren; Kong, Angela; Bain, Carolyn E.; Wang, Ching-Yun; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Foster-Schubert, Karen E.; Wang, Ching-Yun; McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Campbell, Kristin L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Blackburn, George L.] Harvard Univ, Sch Med, Boston, MA USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015; Biguzzi, Felipe/E-4724-2015
OI Duggan, Catherine/0000-0001-7369-4021;
FU National Cancer Institute (NCI) NIH [R01 CA102504, U54-CA116847]; NIH
[5KL2RR025015-03]; NCI [R25 CA94880]
FX This study was funded by National Cancer Institute (NCI) NIH grants R01
CA102504 and U54-CA116847. K. E. F. received support from NIH
5KL2RR025015-03, A. K. was supported by NCI R25 CA94880. The authors
thank the study participants for their time and dedication to the study.
NR 45
TC 72
Z9 73
U1 2
U2 38
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2012
VL 20
IS 8
BP 1628
EP 1638
DI 10.1038/oby.2011.76
PG 11
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 980UY
UT WOS:000306920900012
PM 21494229
ER
PT J
AU Subak, LL
Pinto, AM
Wing, RR
Nakagawa, S
Kusek, JW
Herman, WH
Kuppermann, M
AF Subak, Leslee L.
Pinto, Angela Marinilli
Wing, Rena R.
Nakagawa, Sanae
Kusek, John W.
Herman, William H.
Kuppermann, Miriam
CA Program Reduce Incontinence Diet
TI Decrease in Urinary Incontinence Management Costs in Women Enrolled in a
Clinical Trial of Weight Loss to Treat Urinary Incontinence
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
AB OBJECTIVE: To estimate the effect of a decrease in urinary incontinence (UI) frequency on UI management costs among women enrolled in a clinical trial of a weight loss intervention and to identify factors that predict change in cost.
METHODS: This is a secondary cohort analysis of 338 obese and overweight women with 10 or more weekly episodes of UI enrolled in an 18-month randomized clinical trial of a weight loss intervention compared with a structured education program to treat UI. Quantities of resources used for incontinence management, including pads, additional laundry, and dry cleaning, were reported by participants. Direct costs for UI management ("cost") were calculated by multiplying resources used by national resource costs (in 2006 U. S. dollars). Randomized groups were combined to examine the effects of change in incontinence frequency on cost. Possible predictors of change in cost were examined using generalized estimating equations controlling for factors associated with change in cost in univariable analyses.
RESULTS: Mean age +/- standard deviation was 53 +/- 10 years and baseline weight was 97 +/- 17 kg. Mean weekly UI frequency was 24 +/- 18 at baseline and decreased by 37% at 6 months and 60% at 18 months' follow-up (both P<.001). At baseline, adjusted mean cost was $7.76 +/- $14 per week, with costs increasing significantly with greater incontinence frequency. Mean cost decreased by 54% at 6 months and 81% at 18 months (both P<.001). In multivariable analyses, cost independently decreased by 23% for each decrease of seven UI episodes per week and 21% for each 5 kg of weight lost (P<.001 for both).
CONCLUSION: In obese and overweight women enrolled in a clinical trial of weight loss for UI, incontinence management cost decreased by 81% at 18 months ($ 327 per woman per year) and was strongly and independently associated with decreasing incontinence frequency. (Obstet Gynecol 2012; 120: 277-83) DOI:10.1097/AOG.0b013e31825dd268
C1 [Subak, Leslee L.] UCSF, Mt Zion Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94115 USA.
Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
CUNY, Baruch Coll, Dept Psychol, New York, NY 10021 USA.
Miriam Hosp, Providence, RI 02906 USA.
NIDDKD, Bethesda, MD 20892 USA.
Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
RP Subak, LL (reprint author), UCSF, Mt Zion Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA.
EM subakl@obgyn.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK067860, U01 DK067861, U01 DK067862]; [5RO1 DK070196]
FX Supported by grant number 5RO1 DK070196. The Program to Reduce
Incontinence by Diet and Exercise (PRIDE) was supported by grant numbers
U01DK067860, U01 DK067861, and U01 DK067862 from the National Institute
of Diabetes and Digestive and Kidney Diseases. Funding for PRIDE was
also provided by the Office of Research on Women's Health, National
Institutes of Health.
NR 22
TC 6
Z9 6
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2012
VL 120
IS 2
BP 277
EP 283
DI 10.1097/AOG.0b013e31825dd268
PN 1
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 978BF
UT WOS:000306713100012
PM 22825085
ER
PT J
AU Serafine, KM
Briscione, MA
Rice, KC
Riley, AL
AF Serafine, Katherine M.
Briscione, Maria A.
Rice, Kenner C.
Riley, Anthony L.
TI Dopamine mediates cocaine-induced conditioned taste aversions as
demonstrated with cross-drug preexposure to GBR 12909
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Cocaine; GBR 12909; Conditioned taste aversions; US preexposure;
Dopamine
ID STIMULUS PROPERTIES; PLACE PREFERENCE; AMPHETAMINE; MORPHINE; ETHANOL;
RATS; NOREPINEPHRINE; INVOLVEMENT; FLUVOXAMINE; MECHANISMS
AB Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. It has been suggested that its inhibitory effects at one of the monoamine transporters may be mediating this suppression. Using the cross-drug preexposure preparation, the present series of studies examined a possible role of dopamine (DA) in this effect. Male Sprague-Dawley rats were exposed to cocaine (18 mg/kg; Experiment 1) or the selective DA transporter (DAT) inhibitor GBR 12909 (50 mg/kg; Experiment 2) prior to the pairing of a novel saccharin solution with injections of GBR 12909 (32 mg/kg), cocaine (18 mg/kg) or vehicle in a conditioned taste aversion (CTA) procedure. Preexposure to cocaine attenuated aversions induced by itself but not aversions induced by GBR 12909 (Experiment 1). Conversely, preexposure to GBR 12909 attenuated aversions induced by itself and cocaine (Experiment 2). This asymmetry suggests that cocaine and GBR 12909 induce CTAs via similar, but non-identical,. mechanisms. These data are discussed in the context of previous work demonstrating roles for dopamine, norepinephrine and serotonin in cocaine-induced CTAs. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Serafine, Katherine M.; Briscione, Maria A.; Riley, Anthony L.] American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
[Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD 20852 USA.
[Rice, Kenner C.] NIAAA, Bethesda, MD 20852 USA.
RP Serafine, KM (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, 4400 Mass Ave NW, Washington, DC 20016 USA.
EM kserafine@gmail.com
OI Serafine, Katherine/0000-0002-5099-8505
FU Mellon Foundation; Intramural Research Programs of the National
Institute on Drug Abuse; National Institute on Alcohol Abuse and
Alcoholism
FX This work was supported in part by a grant from the Mellon Foundation to
Anthony L. Riley. A portion of this work was supported by the Intramural
Research Programs of the National Institute on Drug Abuse and the
National Institute on Alcohol Abuse and Alcoholism (K.C.R.). Requests
for reprints should be sent to Katherine M. Serafine, Psychopharmacology
laboratory, Department of Psychology, American University, Washington,
DC 20016 (or kserafine@gmail.com).
NR 46
TC 4
Z9 4
U1 4
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD AUG
PY 2012
VL 102
IS 2
BP 269
EP 274
DI 10.1016/j.pbb.2012.04.012
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 978WH
UT WOS:000306776000013
PM 22579912
ER
PT J
AU Zhou, DW
Chung, S
Miller, M
Le Grice, S
Wlodawer, A
AF Zhou, Dongwen
Chung, Suhman
Miller, Maria
Le Grice, Stuart
Wlodawer, Alexander
TI Crystal structures of the reverse transcriptase-associated ribonuclease
H domain of xenotropic murine leukemia-virus related virus
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Zhou, Dongwen; Miller, Maria; Wlodawer, Alexander] NCI, MCL PSS, Frederick, MD 21701 USA.
[Chung, Suhman; Le Grice, Stuart] NCI, Retroviral Replicat Lab, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 106
EP 107
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800139
ER
PT J
AU Waybright, T
Xiao, Z
Xu, X
Faupel-Badger, J
AF Waybright, Timothy
Xiao, Zhen
Xu, Xia
Faupel-Badger, Jessica
TI Quantitation of Prolactin using Multiple Reaction Monitoring (MRM) Mass
Spectrometry
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Waybright, Timothy; Xiao, Zhen; Xu, Xia] SAIC, Lab Prote & Analyt Technol, Frederick, MD USA.
[Faupel-Badger, Jessica] NCI, Canc Prevent Fellowship Program, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 111
EP 112
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800151
ER
PT J
AU Liang, YH
Lavoie, M
Abou Elela, S
Ji, XH
AF Liang, Yu-He
Lavoie, Mathieu
Abou Elela, Sherif
Ji, Xinhu
TI Structural Basis for Sequence Specificity and Product Length of Yeast
Ribonuclease III
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Liang, Yu-He; Ji, Xinhu] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Lavoie, Mathieu; Abou Elela, Sherif] Univ Sherbrooke, Dept Microbiol, Sch Med, Sherbrooke, PQ J1K 2R1, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 117
EP 117
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800164
ER
PT J
AU Kurussi, SR
Waugh, D
AF Kurussi, Sreejith Raran
Waugh, David
TI Mechanistic View of Solubility Enhancement by E. coli MBP: Role as a
Unique "Holdase" Rather than a "Foldase"
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Kurussi, Sreejith Raran; Waugh, David] Frederick Natl Lab Canc Res, MCL, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 191
EP 191
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800344
ER
PT J
AU Gahl, R
Tekle, E
Tjandra, N
AF Gahl, Robert
Tekle, Ephrem
Tjandra, Nico
TI Detection of Conformational Changes in the Apoptotic Protein Bax Upon
Insertion into the Mitochondrial Membrane
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Gahl, Robert; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Tekle, Ephrem] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 193
EP 193
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800348
ER
PT J
AU Lountos, G
Tropea, J
Waugh, D
AF Lountos, George
Tropea, Joseph
Waugh, David
TI Structure of the cytoplasmic domain of Yersinia pestis YscD, an
essential component of the type III secretion system
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Lountos, George] Frederick Natl Lab Canc Res, SAIC Frederick, Basic Sci Program, Frederick, MD 21702 USA.
[Lountos, George; Tropea, Joseph; Waugh, David] Frederick Natl Lab Canc Res, Macromol Crystallog Lab, Frederick, MD USA.
RI Lountos, George/B-3983-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 194
EP 194
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800352
ER
PT J
AU McGlinchey, R
Jiang, ZP
Lee, J
AF McGlinchey, Ryan
Jiang, Zhiping
Lee, Jennifer
TI Unraveling the Role of C-terminal Glutamates During Fibril Formation of
a Functional Amyloid
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [McGlinchey, Ryan; Jiang, Zhiping; Lee, Jennifer] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 199
EP 200
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800365
ER
PT J
AU Yap, T
Velayati, A
Sidransky, E
Lee, J
AF Yap, Thai
Velayati, Arash
Sidransky, Ellen
Lee, Jennifer
TI Mapping alpha-synuclein-glucocerebrosidase interaction on the membrane
interface
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Yap, Thai; Lee, Jennifer] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Velayati, Arash; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 205
EP 205
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800379
ER
PT J
AU Zhang, YH
Li, ZG
Sacks, D
Ames, J
AF Zhang, Yonghong
Li, Zhigang
Sacks, David
Ames, James
TI Structural Basis for Ca2+-induced Activation and Dimerization of
Estrogen Receptor Alpha by Calmodulin
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Zhang, Yonghong; Ames, James] Univ Calif Davis, Davis, CA 95616 USA.
[Li, Zhigang; Sacks, David] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 205
EP 205
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800380
ER
PT J
AU Gruschus, J
Yap, TL
Velayati, A
Sidransky, E
Lee, J
AF Gruschus, James
Thai Leong Yap
Velayati, Arash
Sidransky, Ellen
Lee, Jennifer
TI Mapping the alpha-Synuclein-Glucocerebrosidase-Saposin C Interface using
Saturation Transfer NMR Spectroscopy
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [Gruschus, James; Thai Leong Yap; Lee, Jennifer] NHLBI, NIH, Bethesda, MD 20892 USA.
[Velayati, Arash; Sidransky, Ellen] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 207
EP 207
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800384
ER
PT J
AU de Silva, U
Chattopadhyay, M
Tabor, H
Davies, D
AF de Silva, Udesh
Chattopadhyay, Manas
Tabor, Herbert
Davies, David
TI Ornithine decarboxylase and antizyme interaction interface shows
critical residues that are important for ornithine decarboxylase
inhibition of activity and binding
SO PROTEIN SCIENCE
LA English
DT Meeting Abstract
CT 26th Annual Symposium of the Protein-Society
CY AUG 05-08, 2012
CL San Diego, CA
SP Prot Soc, Genentech, BioSilta, Aviv Biomed, Inc, Jasco, Purtein, Wyatt Technol Corp, Emerald Biosyst
C1 [de Silva, Udesh; Davies, David] NIDDK, LMB, NIH, Bethesda, MD USA.
[Chattopadhyay, Manas; Tabor, Herbert] NIDDK, LBG, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2012
VL 21
SU 1
SI SI
BP 227
EP 227
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982CR
UT WOS:000307019800432
ER
PT J
AU Kim, HW
Cheon, Y
Modi, HR
Rapoport, SI
Rao, JS
AF Kim, Hyung-Wook
Cheon, Yewon
Modi, Hiren R.
Rapoport, Stanley I.
Rao, Jagadeesh S.
TI Effects of chronic clozapine administration on markers of arachidonic
acid cascade and synaptic integrity in rat brain
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Atypical; Antipsychotic; Arachidonic acid; BDNF; Bipolar disorder;
Drebrin; Cyclooxygenase; Rat; Clozapine; Brain; Docosahexaenoic;
Schizophrenia; Mood stabilizer; iPLA(2); PGE(2)
ID GROUP-SPECIFIC ASSAYS; PHOSPHOLIPASE A(2); DOCOSAHEXAENOIC ACID;
FRONTAL-CORTEX; UNANESTHETIZED RATS; CHRONIC LITHIUM; RECEPTOR
OCCUPANCY; WEIGHT-GAIN; SCHIZOPHRENIC-PATIENTS; INSULIN-SECRETION
AB The mode of action of clozapine, an atypical antipsychotic approved for treating schizophrenia (SZ) and used for bipolar disorder (BD) mania, remains unclear. We tested for overlap with the actions of the mood stabilizers, lithium, carbamazepine and valproate, which downregulate arachidonic acid (AA) cascade markers in rat brain and upregulate BDNF. AA cascade markers are upregulated in BD and SZ postmortem BD brain in association with neuroinflammation and synaptic loss, while BDNF is decreased.
Rats were injected intraperitoneally with a therapeutically relevant dose of clozapine (10 mg/kg/day) or with saline for 30 days, and AA cascade and synaptic markers and BDNF were measured in the brain.
Compared with saline-injected rats, chronic clozapine increased brain activity, mRNA and protein levels of docosahexaenoic acid (DHA)-selective calcium-independent phospholipase A(2) type VIA (iPLA(2)), mRNA and protein levels of BDNF and of the postsynaptic marker, drebrin, while decreasing cyclooxygenase (COX) activity and concentration of prostaglandin E-2 (PGE(2)), a proinflammatory AA metabolite. Activity and expression of AA-selective calcium-dependent cytosolic cPLA(2) type IVA and of secretory sPLA(2) Type II were unchanged.
These results show overlap with effects of mood stabilizers with regard to downregulation of COX activity and PGE(2) and to increased BDNF and suggest a common action against the reported neuropathology of BD and SZ. The increased iPLA(2) expression following clozapine suggests increased production of anti-inflammatory DHA metabolites, and, with increased BDNF and drebrin, clear neuroprotective action.
C1 [Kim, Hyung-Wook; Cheon, Yewon; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Kim, HW (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, Box 357234,1705 Pacific St, Seattle, WA 98195 USA.
EM peterkhw@gmail.com
FU National Institute on Aging, NIH
FX This research was supported entirely by the Intramural Research Program
of the National Institute on Aging, NIH. The authors thank the NIH
Fellows' Editorial Board for editorial assistance.
NR 74
TC 10
Z9 10
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2012
VL 222
IS 4
BP 663
EP 674
DI 10.1007/s00213-012-2671-7
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 979NQ
UT WOS:000306827100009
PM 22414961
ER
PT J
AU McCollough, CH
Chen, GH
Kalender, W
Leng, S
Samei, E
Taguchi, K
Wang, G
Yu, LF
Pettigrew, RI
AF McCollough, Cynthia H.
Chen, Guang Hong
Kalender, Willi
Leng, Shuai
Samei, Ehsan
Taguchi, Katsuyuki
Wang, Ge
Yu, Lifeng
Pettigrew, Roderic I.
TI Achieving Routine Submillisievert CT Scanning: Report from the Summit on
Management of Radiation Dose in CT
SO RADIOLOGY
LA English
DT Article
ID RAY COMPUTED-TOMOGRAPHY; LOW-TUBE-VOLTAGE; CONE-BEAM CT; MULTISLICE
HELICAL CT; NOISE-POWER SPECTRUM; VOLUME-OF-INTEREST; IMAGE-QUALITY;
RECONSTRUCTION ALGORITHM; BREAST TOMOSYNTHESIS; CURRENT MODULATION
AB This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation. (C) RSNA, 2012
C1 [McCollough, Cynthia H.; Leng, Shuai; Yu, Lifeng] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA.
[Chen, Guang Hong] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
[Kalender, Willi] Univ Erlangen Nurnberg, Dept Med Phys, D-91054 Erlangen, Germany.
[Samei, Ehsan] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Taguchi, Katsuyuki] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
[Wang, Ge] Virginia Tech Wake Forest Univ, Sch Biomed Engn & Sci, Blacksburg, VA USA.
[Pettigrew, Roderic I.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP McCollough, CH (reprint author), Mayo Clin, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA.
EM mccollough.cynthia@mayo.edu
FU National Institutes of Health [EB002667, EB004287, EB007288]
FX This research was supported by the National Institutes of Health (grants
EB002667, EB004287, and EB007288).
NR 99
TC 134
Z9 138
U1 5
U2 24
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD AUG
PY 2012
VL 264
IS 2
BP 567
EP 580
DI 10.1148/radiol.12112265
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 977KX
UT WOS:000306660000030
PM 22692035
ER
PT J
AU Kojima, G
Bell, C
Abbott, RD
Launer, L
Chen, RD
Motonaga, H
Ross, GW
Curb, JD
Masaki, K
AF Kojima, Gotaro
Bell, Christina
Abbott, Robert D.
Launer, Lenore
Chen, Randi
Motonaga, Heather
Ross, G. Webster
Curb, J. David
Masaki, Kamal
TI Low Dietary Vitamin D Predicts 34-Year Incident Stroke The Honolulu
Heart Program
SO STROKE
LA English
DT Article
DE dietary vitamin D intake; incident stroke; Japanese-American men;
longitudinal cohort study
ID MIDDLE-AGED MEN; 25-HYDROXYVITAMIN D; JAPANESE ANCESTRY;
CARDIOVASCULAR-DISEASE; D INSUFFICIENCY; NORTH-AMERICA; D DEFICIENCY;
HAWAII; RISK; CALCIUM
AB Background and Purpose-Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease, especially stroke. We examined the relationship between dietary vitamin D intake and 34-year incident stroke.
Methods-The Honolulu Heart Program is a prospective population-based cohort study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the baseline examination in 1965 to 1968. Dietary vitamin D intake was calculated using the Nutritionist IV Version 3 software from a 24-hour dietary recall. Subjects with prevalent stroke were excluded, leaving 7385 men followed through 1999 for incident stroke. Subjects were divided into quartiles of dietary vitamin D for analyses.
Results-During 34 years of follow-up, 960 subjects developed stroke. Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared with the highest (all stroke: 6.38 versus 5.14 per 1000 person-years follow-up, P = 0.030; thromboembolic stroke: 4.36 versus 3.30, P = 0.033). Using Cox regression, adjusting for age, total kilocalories, body mass index, hypertension, diabetes mellitus, pack-years smoking, physical activity index, serum cholesterol, and alcohol intake, those in the lowest quartile had a significantly increased risk of incident stroke (all stroke hazard ratio, 1.22; 95% CI, 1.01-1.47; P = 0.038; thromboembolic stroke hazard ratio, 1.27; 95% CI, 1.01-1.59; P = 0.044) with the highest as the reference. We found no significant associations between dietary vitamin D and hemorrhagic stroke.
Conclusions-Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men. Additional research is needed on vitamin D supplementation to prevent stroke. (Stroke. 2012; 43: 2163-2167.)
C1 [Kojima, Gotaro; Bell, Christina; Abbott, Robert D.; Ross, G. Webster; Curb, J. David; Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn Ctr Excellence Geriatr, Honolulu, HI 96817 USA.
[Bell, Christina; Chen, Randi; Curb, J. David; Masaki, Kamal] Kuakini Med Ctr, Honolulu, HI USA.
[Abbott, Robert D.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
[Launer, Lenore] NIA, Bethesda, MD 20892 USA.
[Motonaga, Heather] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
RP Kojima, G (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn Ctr Excellence Geriatr, 347 N Kuakini St HPM 9, Honolulu, HI 96817 USA.
EM gotarokojima@yahoo.co.jp
FU National Heart, Lung, and Blood Institute [N01-HC-05102]; National
Institute on Aging [N01-AG-4-2149, U01-AG019349]; Office for Research
and Development, Department of Veterans Affairs
FX This study was supported by contract N01-HC-05102 from the National
Heart, Lung, and Blood Institute, contract N01-AG-4-2149, grant
U01-AG019349, and the Intramural Research Program from the National
Institute on Aging, and Office for Research and Development, Department
of Veterans Affairs.
NR 29
TC 21
Z9 23
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD AUG
PY 2012
VL 43
IS 8
BP 2163
EP 2167
DI 10.1161/STROKEAHA.112.651752
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 977UC
UT WOS:000306689300035
PM 22627988
ER
PT J
AU Zimerman, M
Heise, KF
Hoppe, J
Cohen, LG
Gerloff, C
Hummel, FC
AF Zimerman, Maximo
Heise, Kirstin F.
Hoppe, Julia
Cohen, Leonardo G.
Gerloff, Christian
Hummel, Friedhelm C.
TI Modulation of Training by Single-Session Transcranial Direct Current
Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition
of the Paretic Hand
SO STROKE
LA English
DT Article
DE motor learning; rehabilitation; stroke recovery; tDCS
ID NONINVASIVE CORTICAL STIMULATION; MAGNETIC STIMULATION;
BRAIN-STIMULATION; STROKE PATIENTS; DC STIMULATION; RECOVERY;
PLASTICITY; CONSOLIDATION; EXCITABILITY; MEMORY
AB Background and Purpose-Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand.
Method-Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation.
Results-tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P = 0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R-2 = 0.63).
Conclusions-These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke. (Stroke. 2012; 43: 2185-2191.)
C1 [Zimerman, Maximo; Heise, Kirstin F.; Hoppe, Julia; Gerloff, Christian; Hummel, Friedhelm C.] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat BINS Lab, D-20246 Hamburg, Germany.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
RP Hummel, FC (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat BINS Lab, D-20246 Hamburg, Germany.
EM f.hummel@uke.de
OI Heise, Kirstin-Friederike/0000-0003-3666-8531
FU German Academic Exchange Service [A/07/95990]; Alexander von Humboldt
Foundation; Forschungsforderungsfonds Medizin of the University of
Hamburg [NWF-04/07, NWF-11/09]; Kompetenznetz Schlaganfall; German
Research Foundation [SFB 936-C4]
FX This research was supported by a grant from the German Academic Exchange
Service to M.Z. (A/07/95990), the Alexander von Humboldt Foundation
(Feodor-Lynen) to F. C. H., the Forschungsforderungsfonds Medizin of the
University of Hamburg to F. C. H. (NWF-04/07) and to M.Z. (NWF-11/09),
the Kompetenznetz Schlaganfall to C. G., and the German Research
Foundation (SFB 936-C4) to F.C.H.
NR 48
TC 74
Z9 82
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD AUG
PY 2012
VL 43
IS 8
BP 2185
EP U289
DI 10.1161/STROKEAHA.111.645382
PG 12
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 977UC
UT WOS:000306689300039
PM 22618381
ER
PT J
AU Chou, SP
Chun, S
Smith, S
Ruan, J
Li, TK
Grant, BF
AF Chou, S. Patricia
Chun, Sungsoo
Smith, Sharon
Ruan, June
Li, Ting-Kai
Grant, Bridget F.
TI Episodic heavy drinking, problem drinking and injuries - Results of the
WHO/NIAAA collaborative emergency room study in South Korea
SO ALCOHOL
LA English
DT Article
DE Emergency room (ER) study; Episodic heavy drinking; Problem drinking;
Alcohol-related and intentional injury
ID ACUTE ALCOHOL-USE; NONFATAL INJURY; TRAUMA PATIENTS; CASE-CROSSOVER;
CONSUMPTION; PATTERNS; RISK; PREVALENCE; CARE
AB Alcohol is the 5th leading risk factor to the global disease burden and disability and about half of the global alcohol burden was attributable to injuries. Despite a large body of evidence documenting the associations between alcohol and injuries, data from Asian countries including South Korea are sparse. The aim of this study was to investigate the associations between episodic heavy past-year drinking, problem drinking symptomatic of alcohol dependence and alcohol-related and intentional injuries. Data from 1989 injured patients recruited for the WHO/NIAAA Collaborative Study on Alcohol and Injury in South Korea were analyzed with respect to the prevalence rates and associations between injuries and frequency of past-year episodic heavy drinking and problem drinking. In estimating the odds ratios (ORs) and the associated 95% confidence intervals between alcohol intake and injuries multivariable logistic models were employed to adjust for sociodemographic characteristics and selected drinking variables. All analyses were conducted using the SAS 9.2 software. Findings of this study were consistent with prior studies that the risk of alcohol-related or intentional injury was positively associated with the frequency of episodic heavy drinking. The magnitudes of the associations were larger with frequent consumption of 5+ drinks (OR = 4.0 approximately) than with frequent consumption of 12+ drinks (OR = 3.1). Strong associations were also noted between RAPS4-assessed alcohol dependence and alcohol-related and intentional injuries. Further, the prevalence of intentional injury and its association with alcohol increased sharply once the acute alcohol intake exceeded 90 ml. Our results were consistent with prior studies that episodic heavy consumption, acute intoxication and problem drinking are pervasive among emergency room patients. Results of our study also lent support for administering a single-item screener querying consumption of 5+ drinks at a sitting in the past 12 months as a triage tool in Korea. Published by Elsevier Inc.
C1 [Chou, S. Patricia; Smith, Sharon; Ruan, June; Grant, Bridget F.] NIAAA, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Chun, Sungsoo] Sahmyook Univ, Korean Inst Alcohol Problems, Seoul, South Korea.
[Li, Ting-Kai] Duke Univ, Sch Med, Durham, NC USA.
RP Chou, SP (reprint author), NIAAA, LEB, NIH, Div Intramural Clin & Biol Res, 5635 Fishers Lane,3073, Bethesda, MD 20892 USA.
EM pchou@mail.nih.gov
FU U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA); Korean
Ministry of Health Welfare; National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism
FX The WHO/NIAAA Collaborative Emergency Room Study in South Korea is
funded by the U.S. National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and the Korean Ministry of Health & Welfare. This research was
also supported in part by the Intramural Program of the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism.
NR 30
TC 5
Z9 5
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
J9 ALCOHOL
JI Alcohol
PD AUG
PY 2012
VL 46
IS 5
BP 407
EP 413
DI 10.1016/j.alcohol.2012.03.002
PG 7
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 975UP
UT WOS:000306537300001
PM 22579122
ER
PT J
AU Castle, PE
Gravitt, PE
Wentzensen, N
Schiffman, M
AF Castle, Philip E.
Gravitt, Patti E.
Wentzensen, Nicolas
Schiffman, Mark
TI A Descriptive Analysis of Prevalent vs Incident Cervical Intraepithelial
Neoplasia Grade 3 Following Minor Cytologic Abnormalities
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Pap; Cytology; Human papillomavirus (HPV); Cervical intraepithelial
neoplasia (CIN)
ID ATYPICAL SQUAMOUS-CELLS; HUMAN-PAPILLOMAVIRUS DNA; UNDETERMINED
SIGNIFICANCE; RANDOMIZED-TRIAL; LESION TRIAGE; CANCER; PAPANICOLAOU;
MANAGEMENT; WOMEN; COLPOSCOPY
AB Cervical intraepithelial neoplasia grade 3 (CIN 3) is the best proxy in research and screening for invasive cancer risk. Yet the timing of CIN 3 development is uncertain because of measurement errors integral to its diagnosis. We were interested in estimating the proportions of prevalent vs incident CIN 3 within 2 years Winding a minor cytologic abnormality. We estimate that only 17(2.8%) of 613 CIN 3 cases diagnosed during the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS) were incident CIN 3 following an incident human papillomavirus (HPV) infection that persisted until the CIN 3 diagnosis was made. Using prevalent high-grade cytology as a marker of prevalent CIN 3, we estimated that another approximately 23% of CIN 3 cases were incident CIN 3 following a prevalently detected HPV infection that persisted until the CIN 3 diagnosis was made. We concluded that most CIN 3 cases diagnosed within the 2-year time frame were prevalent cases, and most incident CIN 3 cases followed a prevalently detected HPV infection.
C1 [Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC 20005 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Wentzensen, Nicolas; Schiffman, Mark] NCI, Divi Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Castle, PE (reprint author), Amer Soc Clin Pathol Inst, 1225 New York Ave NW,Suite 250, Washington, DC 20005 USA.
FU ARUP Institute of Clinical and Experimental Pathology, Salt Lake City;
Research Program of the National Institutes of Health and National
Cancer Institute; National Cancer Institute, National Institutes of
Health Department of Health and Human Services [CN-55153, CN-55154,
CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55105]
FX This study was supported by funding from the ARUP Institute of Clinical
and Experimental Pathology, Salt Lake City, and in part by the
Intramural Research Program of the National Institutes of Health and
National Cancer Institute.; National Cancer Institute, National
Institutes of Health Department of Health and Human Services contracts
CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159 and
CN-55105 provided support for ALTS. Some of the equipment and supplies
used in these studies were donated or provided at reduced cost by Digene
Corporation, Gaithersburg, MD; Cytyc Corporation, Marlborough, MA;
National Testing Laboratories, Fenton, MO; Den Vu, Tucson, AZ; TriPath
Imaging, Inc, Burlington, NC; and Roche Molecular Systems Inc, Alameda,
CA. We thank the ALTS Group Investigators for their help in planning and
conducting the trial.
NR 24
TC 5
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD AUG
PY 2012
VL 138
IS 2
BP 241
EP 246
DI 10.1309/AJCPNTK6G2PXWHOO
PG 6
WC Pathology
SC Pathology
GA 975UC
UT WOS:000306536000011
PM 22904136
ER
PT J
AU Bi, XF
Zheng, TZ
Lan, Q
Xu, ZJ
Chen, YT
Zhu, GJ
Foss, F
Kim, C
Dai, M
Zhao, P
Holford, T
Leaderer, B
Boyle, P
Deng, Q
Chanock, SJ
Rothman, N
Zhang, YW
AF Bi, Xiaofeng
Zheng, Tongzhang
Lan, Qing
Xu, Zhijian
Chen, Yingtai
Zhu, Gongjian
Foss, Francine
Kim, Christopher
Dai, Min
Zhao, Ping
Holford, Theodore
Leaderer, Brian
Boyle, Peter
Deng, Qian
Chanock, Stephen J.
Rothman, Nathaniel
Zhang, Yawei
TI Genetic polymorphisms in IL10RA and TNF modify the association between
blood transfusion and risk of non-Hodgkin lymphoma
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; B-CELL LYMPHOMA; NF-KAPPA-B; INTERLEUKIN-10
RECEPTOR; CYTOKINE POLYMORPHISMS; CANCER; PATHWAY; IL-10; ALPHA;
SUSCEPTIBILITY
AB We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes may modify the association between blood transfusion and risk of non-Hodgkin lymphoma (NHL). Compared with women without blood transfusion, women with a history of transfusion had an increased risk of NHL if they carried IL10RA (rs9610) GG genotype [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.13.2] or TNF (rs1800629) AG/AA genotypes (OR = 1.6, 95% CI: 0.92.7). We also found women with a history of transfusion had a decreased risk of NHL if they carried IL10RA (rs9610) AG/AA genotypes (OR = 0.6, 95% CI: 0.40.9) or TNF (rs1800629) GG genotype (OR = 0.7, 95% CI: 0.51.0). A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. Statistically significant interactions with blood transfusion were observed for IL10RA (rs9610) (Pforinteraction = 0.003) and TNF (rs1800629) (Pforinteraction = 0.012) for NHL overall and IL10RA (rs9610) (Pforinteraction = 0.001) and TNF (rs1800629) (Pforinteraction = 0.019) for B-cell lymphoma. The results suggest that genetic polymorphisms in TNF and IL10RA genes may modify the association between blood transfusion and NHL risk. Am. J. Hematol. 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Bi, Xiaofeng; Zheng, Tongzhang; Kim, Christopher; Holford, Theodore; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Bi, Xiaofeng; Xu, Zhijian; Chen, Yingtai; Dai, Min; Zhao, Ping] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Lan, Qing; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Zhu, Gongjian] Gansu Prov Acad Med Sci, Gansu Prov Tumor Hosp, Lanzhou, Peoples R China.
[Foss, Francine] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Boyle, Peter] Int Prevent Res Inst, Lyon, France.
[Deng, Qian] Sichuan Univ, Sch Publ Hlth, Chengdu 610064, Peoples R China.
[Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
RI Boyle, Peter/A-4380-2014
OI Boyle, Peter/0000-0001-6251-0610
FU NIH [CA62006, 1D43TW008323-01, 1D43TW007864-01, HD70324-01,
CA165923-01]; National Institutes of Health (NIH), National Cancer
Institute
FX Contract grant sponsor: NIH; Contract grant numbers: CA62006,
1D43TW008323-01, 1D43TW007864-01, HD70324-01, CA165923-01; Contract
grant sponsor: Intramural Research Program of the National Institutes of
Health (NIH), National Cancer Institute.
NR 41
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2012
VL 87
IS 8
BP 766
EP 769
DI 10.1002/ajh.23244
PG 4
WC Hematology
SC Hematology
GA 975BW
UT WOS:000306482700004
PM 22649007
ER
PT J
AU Mitrovic, Z
Perry, AM
Suzumiya, J
Armitage, JO
Au, WY
Coiffier, B
Holte, H
Jaffe, ES
Monserrat, E
Rajan, SK
Savage, KJ
Tobinai, K
Vose, JM
Weisenburger, DD
AF Mitrovic, Zdravko
Perry, Anamarija M.
Suzumiya, Junji
Armitage, James O.
Au, Wing Y.
Coiffier, Bertrand
Holte, Harald
Jaffe, Elaine S.
Monserrat, Emili
Rajan, Sandeep K.
Savage, Kerry J.
Tobinai, Kensei
Vose, Julie M.
Weisenburger, Dennis D.
TI The prognostic significance of lymphopenia in peripheral T-cell and
natural killer/T-cell lymphomas: A study of 826 cases from the
International Peripheral T-cell Lymphoma Project
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID ADVANCED HODGKINS-DISEASE; LEUKEMIA-LYMPHOMA; COUNT; SURVIVAL; SCORE;
LEUKEMIA/LYMPHOMA; TRANSPLANTATION; CHEMOTHERAPY; LYMPHOCYTES; FEATURES
AB Lymphopenia is a marker of inferior survival in patients with various malignancies. However, the prognostic significance of lymphopenia in peripheral T-cell lymphoma (PTCL) is unclear. We analyzed the prognostic significance of lymphopenia in 826 patients with different types of PTCL and natural killer/T-cell lymphoma (NKTCL) from the International Peripheral T-cell Lymphoma Project. Lymphopenia was defined as an absolute lymphocyte count of less than 1,000 cells per microliter. The overall frequency of lymphopenia was 35.3%, ranging from 21.1% in ALK+ anaplastic large cell lymphoma (ALCL) to 47.5% in angioimmunoblastic T-cell lymphoma (AITL). Lymphopenia was independently associated with an inferior overall survival (OS) in patients with the lymphoma type of adult T-cell leukemia/lymphoma (ATLL), with a 2-year OS of 15% versus 40% for those without lymphopenia (P < 0.001). Lymphopenia was also an adverse predictor of survival in PTCL, not otherwise specified, but was associated with other unfavorable prognostic factors. A trend toward inferior survival for lymphopenic patients was also observed in AITL, ALK- ALCL and extranasal NKTCL lymphoma, whereas no difference in survival was found in nasal NKTCL, ALK+ ALCL, or enteropathy-associated T-cell lymphoma. In this study, lymphopenia was identified as a new adverse prognostic factor in the lymphoma type of ATLL. Am. J. Hematol. 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Mitrovic, Zdravko; Perry, Anamarija M.; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Mitrovic, Zdravko] Univ Zaragoza, Sch Med, Zagreb, Croatia.
[Suzumiya, Junji] Fukuoka Univ, Chikushi Hosp, Dept Internal Med, Fukuoka 81401, Japan.
[Armitage, James O.; Rajan, Sandeep K.; Vose, Julie M.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA.
[Au, Wing Y.] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Coiffier, Bertrand] Ctr Hosp Lyon Sud, Dept Hematol, Lyon, France.
[Holte, Harald] Univ Hosp Oslo, Dept Oncol, Oslo, Norway.
[Jaffe, Elaine S.] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Monserrat, Emili] Univ Barcelona Hosp, Inst Hematol & Oncol, Barcelona, Spain.
[Savage, Kerry J.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Tobinai, Kensei] Natl Canc Ctr, Hematol & Stem Cell Transplantat Div, Tokyo, Japan.
RP Weisenburger, DD (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM dweisenb@unmc.edu
OI Jaffe, Elaine/0000-0003-4632-0301
NR 35
TC 14
Z9 16
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2012
VL 87
IS 8
BP 790
EP 794
DI 10.1002/ajh.23205
PG 5
WC Hematology
SC Hematology
GA 975BW
UT WOS:000306482700008
PM 22488678
ER
PT J
AU McGrath, LM
Mustanski, B
Metzger, A
Pine, DS
Kistner-Griffin, E
Cook, E
Wakschlag, LS
AF McGrath, L. M.
Mustanski, B.
Metzger, A.
Pine, D. S.
Kistner-Griffin, E.
Cook, E.
Wakschlag, L. S.
TI A latent modeling approach to genotype-phenotype relationships: maternal
problem behavior clusters, prenatal smoking, and MAOA genotype
SO ARCHIVES OF WOMENS MENTAL HEALTH
LA English
DT Article
DE Female problem behavior; Antisocial behavior; Prenatal smoking;
Monoamine oxidase A (MAOA); Gene x environment interaction
ID X-CHROMOSOME INACTIVATION; OXIDASE-A GENE; MONOAMINE-OXIDASE;
ANTISOCIAL-BEHAVIOR; CONDUCT DISORDER; FUNCTIONAL POLYMORPHISM;
EXTERNALIZING SPECTRUM; SCREENING-TEST; LUNG-FUNCTION; SEXUAL-ABUSE
AB This study illustrates the application of a latent modeling approach to genotype-phenotype relationships and gene x environment interactions, using a novel, multidimensional model of adult female problem behavior, including maternal prenatal smoking. The gene of interest is the monoamine oxidase A (MAOA) gene which has been well studied in relation to antisocial behavior. Participants were adult women (N = 192) who were sampled from a prospective pregnancy cohort of non-Hispanic, white individuals recruited from a neighborhood health clinic. Structural equation modeling was used to model a female problem behavior phenotype, which included conduct problems, substance use, impulsive-sensation seeking, interpersonal aggression, and prenatal smoking. All of the female problem behavior dimensions clustered together strongly, with the exception of prenatal smoking. A main effect of MAOA genotype and a MAOA x physical maltreatment interaction were detected with the Conduct Problems factor. Our phenotypic model showed that prenatal smoking is not simply a marker of other maternal problem behaviors. The risk variant in the MAOA main effect and interaction analyses was the high activity MAOA genotype, which is discrepant from consensus findings in male samples. This result contributes to an emerging literature on sex-specific interaction effects for MAOA.
C1 [McGrath, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, Boston, MA 02114 USA.
[McGrath, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Mustanski, B.; Wakschlag, L. S.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Metzger, A.] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA.
[Pine, D. S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Kistner-Griffin, E.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Cook, E.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
RP McGrath, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, Simches Res Bldg,6th Floor,185 Cambridge St, Boston, MA 02114 USA.
EM mcgrath@pngu.mgh.harvard.edu
FU NIDA NIH HHS [R01 DA015223, R01 DA023653]
NR 80
TC 13
Z9 13
U1 1
U2 8
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 1434-1816
J9 ARCH WOMEN MENT HLTH
JI Arch. Womens Ment. Health
PD AUG
PY 2012
VL 15
IS 4
BP 269
EP 282
DI 10.1007/s00737-012-0286-y
PG 14
WC Psychiatry
SC Psychiatry
GA 975CI
UT WOS:000306484000004
PM 22610759
ER
PT J
AU Klausmeyer, P
McCloud, TG
Scudiero, DA
Currens, MJ
Cardellina, JH
Shoemaker, RH
AF Klausmeyer, Paul
McCloud, Thomas G.
Scudiero, Dominic A.
Currens, Michael J.
Cardellina, John H., II
Shoemaker, Robert H.
TI Discovery and preliminary SAR of bisbenzylisoquinoline alkaloids as
inducers of C/EBP alpha
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Bisbenzylisoquinoline alkaloids; C/EBP alpha; Gyrocarpus jacquinii;
Structure-activity relationships
ID BINDING PROTEIN-ALPHA; TRANSCRIPTION FACTOR; INHIBITORS
AB A high throughput in vitro screen has been developed to identify substances that induce expression of C/EBP alpha in tumor cells. An extract of the fruit of Gyrocarpus jacquinii showed induction of C/EBP alpha activity that was attributed to the bisbenzylisoquinoline (BBIQ) alkaloid pheanthine (13) by dereplication analysis. The research project was broadened to assess the effect of other natural BBIQ structural types occurring outside the genus Gyrocarpus. Several of the 28 compounds assayed showed enhancement of C/EBP alpha induction in U937 cells. The results of this study should encourage future efforts toward obtaining and screening a larger set of both natural and synthetic analogs of this interesting group of alkaloids. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Klausmeyer, Paul; McCloud, Thomas G.] SAIC Frederick Inc, Nat Prod Support Grp, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Scudiero, Dominic A.] SAIC Frederick Inc, Vitro Cell Line Screening Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Currens, Michael J.; Cardellina, John H., II; Shoemaker, Robert H.] Frederick Natl Lab Canc Res, Div Canc Treatment & Diag, Dev Therapeut Program, Screening Technol Branch, Frederick, MD 21702 USA.
RP Klausmeyer, P (reprint author), SAIC Frederick Inc, Nat Prod Support Grp, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM klausmeyerp@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. N01-CO-12400. This research was supported in part by the
Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. We gratefully acknowledge G.M. Cragg and D.D. Soejarto
for the contract collection, S. Clopper for performing the C/EBP alpha
biological screen, J. Britt for robotics support, J.A. Laudeman, T.E.
Silvers and M. Selby for bioassay data processing.
NR 12
TC 2
Z9 2
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 1
PY 2012
VL 20
IS 15
BP 4646
EP 4652
DI 10.1016/j.bmc.2012.06.017
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 975AX
UT WOS:000306480200005
PM 22766217
ER
PT J
AU Tsigginou, A
Bimpaki, E
Nesterova, M
Horvath, A
Boikos, S
Lyssikatos, C
Papageorgiou, C
Dimitrakakis, C
Rodolakis, A
Stratakis, CA
Antsaklis, A
AF Tsigginou, A.
Bimpaki, E.
Nesterova, M.
Horvath, A.
Boikos, S.
Lyssikatos, C.
Papageorgiou, C.
Dimitrakakis, C.
Rodolakis, A.
Stratakis, C. A.
Antsaklis, A.
TI PRKAR1A gene analysis and protein kinase A activity in endometrial
tumors
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
ID CARNEY-COMPLEX; MUTATIONS; EXPRESSION; SUBUNIT; CANCER; ACTIVATION;
ENDOCRINE; ALPHA
AB PRKAR1A codes for the type 1a regulatory subunit (RI alpha) of the cAMP-dependent protein kinase A (PKA), an enzyme with an important role in cell cycle regulation and proliferation. PKA dysregulation has been found in various tumors, and PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias. In this study, we investigated PKA activity and the PRKAR1A gene in normal and tumor endometrium. Specimens were collected from 31 patients with endometrial cancer. We used as controls 41 samples of endometrium that were collected from surrounding normal tissues or from women undergoing gynecological operations for other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and studied PKA subunit expression; we also determined PKA activity and cAMP binding. PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels, both RI alpha and those of regulatory subunit type 2b (RII beta), were lower in tumor samples; cAMP binding was also lower in tumors compared with normal endometrium (P < 0.01). Free PKA activity was higher in tumor samples compared with that of control tissue (P < 0.01). There are significant PKA enzymatic abnormalities in tumors of the endometrium compared with surrounding normal tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting PKA function ought to be explored. Endocrine-Related Cancer (2012) 19 457-462
C1 [Bimpaki, E.; Nesterova, M.; Horvath, A.; Boikos, S.; Lyssikatos, C.; Stratakis, C. A.] NICHD, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bethesda, MD 20892 USA.
[Dimitrakakis, C.] NICHD, Dev Endocrinol Branch, NIH, CRC, Bethesda, MD 20892 USA.
[Tsigginou, A.; Papageorgiou, C.; Dimitrakakis, C.; Rodolakis, A.; Antsaklis, A.] Univ Athens, Sch Med, Alexandra Hosp, Dept Obstet & Gynecol 1, Athens 11528, Greece.
RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); National Institutes of Health (NIH)
[Z01-HD-000642-04]
FX This work was supported, in part, by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) and intramural
National Institutes of Health (NIH) project Z01-HD-000642-04 to Dr C A
Stratakis.
NR 17
TC 1
Z9 2
U1 0
U2 1
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD AUG
PY 2012
VL 19
IS 4
BP 457
EP 462
DI 10.1530/ERC-11-0328
PG 6
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 975IJ
UT WOS:000306504600005
PM 22461635
ER
PT J
AU Flores, R
Shi, JX
Gail, MH
Ravel, J
Goedert, JJ
AF Flores, Roberto
Shi, Jianxin
Gail, Mitchell H.
Ravel, Jacques
Goedert, James J.
TI Assessment of the human faecal microbiota: I. Measurement and
reproducibility of selected enzymatic activities
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Stool; reproducibility; ss-glucosidase activity; ss-glucuronidase
activity
ID HUMAN FECES; BACTERIA; ENZYMES; POLYSACCHARIDE; CARBOHYDRATE; COLON;
MICE
AB Eur J Clin Invest 2012 Abstract Background The intestinal microbial community has major effects on human health, but optimal research methods are unsettled. To facilitate epidemiologic and clinical research, we sought to optimize conditions and to assess reproducibility of selected core functions of the distal gut microbiota, beta-glucuronidase and beta-glucosidase bioactivities. Methods and results A colorimetric kinetic method was optimized and used to quantify activities of beta-glucuronidase and beta-glucosidase in human faeces. Enzyme detection was optimal with neutral pH, snap freezing in liquid nitrogen and rapid thawing to 37 degrees C before protein extraction. Enzymatic stability was assessed by delayed freezing for 248 h to mimic field settings. Activities decayed approximately 20% within 2 h and 40% within 4 h at room temperature. To formally assess reproducibility, 51 volunteers (25 men; mean age 39) used two devices to self-collect and rapidly chill four replicates of a stool. Devices were compared for mean enzymatic activities and intraclass correlation coefficients (ICC) in paired replicates of the self-collected specimens. Reproducibility was excellent with both devices for beta-glucuronidase (ICC 0.92). The larger collection device had significantly higher reproducibility for beta-glucosidase (ICC 0.92 vs. 0.76, P < 0.0001) and higher mean activities for both enzymes (P < 0.0001). Conclusions Optimal measurement of these core activities of the microbiota required a sufficient quantity of rapidly chilled or frozen specimens collected in phosphate buffered saline at pH7.0. Application of these methods to clinical and epidemiologic research could provide insights on how the intestinal microbiota affects human health.
C1 [Flores, Roberto] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Flores, Roberto] Univ Maryland, Sch Med, Canc Prevent Fellowship Program, Natl Canc Inst, Baltimore, MD 21201 USA.
[Shi, Jianxin; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
RP Flores, R (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7067, Rockville, MD 20892 USA.
EM floresr2@mail.nih.gov
OI Ravel, Jacques/0000-0002-0851-2233
FU National Cancer Institute, National Institutes of Health [Z01-CP010214]
FX This project (Z01-CP010214) was funded by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health.
NR 21
TC 9
Z9 11
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD AUG
PY 2012
VL 42
IS 8
BP 848
EP 854
DI 10.1111/j.1365-2362.2012.02660.x
PG 7
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 975FF
UT WOS:000306492200006
PM 22409163
ER
PT J
AU Flores, R
Shi, JX
Gail, MH
Gajer, P
Ravel, J
Goedert, JJ
AF Flores, Roberto
Shi, Jianxin
Gail, Mitchell H.
Gajer, Pawel
Ravel, Jacques
Goedert, James J.
TI Assessment of the human faecal microbiota: II. Reproducibility and
associations of 16S rRNA pyrosequences
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Alpha diversity; bacterial phylogenetics; beta diversity; body mass
index; medications; microbiome
ID DNA-EXTRACTION METHODS; DISTAL GUT MICROBIOTA; BACTERIAL; RECOVERY;
PROJECT; SAMPLES; TOOLS; TWINS
AB Eur J Clin Invest 2012; Abstract Background: We conducted a pilot study of reproducibility and associations of microbial diversity and composition in faecal microbial DNA. Methods and results: Participants (25 men and 26 women, aged 1765 years) provided questionnaire data and multiple samples of one stool collected with two Polymedco and two Sarstedt devices preloaded with RNAlater. 16S rRNA genes in each faecal DNA aliquot were amplified, sequenced (Roche/454 Life Sciences) and assigned to taxa. Devices were compared for ease of use and reproducibility [intraclass correlation coefficient (ICC)] between duplicate aliquots on diversity and taxonomic assignment. Associations were tested by linear regression. Both collection devices were easy to use. Both alpha diversity (Shannon index) and beta diversity (UniFrac) were higher between than within duplicates (P = 10-8) and did not differ significantly by device (P = 0.62). Reproducibility was good (ICC=0.77) for alpha diversity and taxonomic assignment to the most abundant phyla, Firmicutes and Bacteroidetes (71.5% and 25.0% of sequences, respectively), but reproducibility was low (ICC=0.48) for less abundant taxa. Alpha diversity was lower with nonantibiotic prescription medication (P = 0.02), with younger age (P = 0.03) and marginally with higher body mass index (P = 0.08). Conclusions: With sampling from various parts of a stool, both devices provided good reproducibility on overall microbial diversity and classification for the major phyla, but not for minor phyla. Implementation of these methods should provide insights into how broad microbial parameters, but not necessarily rare microbes, affect risk of various conditions.
C1 [Flores, Roberto; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Flores, Roberto] NCI, Canc Prevent Fellowship Program, Baltimore, MD USA.
[Shi, Jianxin; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Gajer, Pawel; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
RP Goedert, JJ (reprint author), 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
OI Ravel, Jacques/0000-0002-0851-2233
FU National Cancer Institute, National Institutes of Health [Z01-CP010214]
FX This project (Z01-CP010214) was funded by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health.
NR 36
TC 22
Z9 23
U1 2
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD AUG
PY 2012
VL 42
IS 8
BP 855
EP 863
DI 10.1111/j.1365-2362.2012.02659.x
PG 9
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 975FF
UT WOS:000306492200007
PM 22385292
ER
PT J
AU Wang, MY
Zhang, J
Telljohann, R
Jiang, LQ
Wu, J
Monticone, RE
Kapoor, K
Talan, M
Lakatta, EG
AF Wang, Mingyi
Zhang, Jing
Telljohann, Richard
Jiang, Liqun
Wu, James
Monticone, Robert E.
Kapoor, Kapil
Talan, Mark
Lakatta, Edward G.
TI Chronic Matrix Metalloproteinase Inhibition Retards Age-Associated
Arterial Proinflammation and Increase in Blood Pressure
SO HYPERTENSION
LA English
DT Article
DE aging; arterial remodeling; matrix metalloproteinase inhibitor;
endothelin 1; transforming growth factor-beta 1; ets-1; monocyte
chemoattractant protein 1; blood pressure
ID SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; RECEPTOR BLOCKADE; HEART-FAILURE;
RECOMBINANT ADENOVIRUSES; VASCULAR INFLAMMATION; EXTRACELLULAR-MATRIX;
AEROBIC EXERCISE; LIFE-SPAN; DYSFUNCTION
AB Age-associated arterial remodeling involves arterial wall collagen deposition and elastin fragmentation, as well as an increase in arterial pressure. This arterial remodeling is linked to proinflammatory signaling, including transforming growth factor-beta 1, monocyte chemoattractant protein 1, and proendothelin 1, activated by extracellular matrix metalloproteinases (MMPs) and orchestrated, in part, by the transcriptional factor ets-1. We tested the hypothesis that inhibition of MMP activation can decelerate the age-associated arterial proinflammation and its attendant increase in arterial pressure. Indeed, chronic administration of a broad-spectrum MMP inhibitor, PD166739, via a daily gavage, to 16-month-old rats for 8 months markedly blunted the expected age-associated increases in arterial pressure. This was accompanied by the following: (1) inhibition of the age-associated increases in aortic gelatinase and interstitial collagenase activity in situ; (2) preservation of the elastic fiber network integrity; (3) a reduction of collagen deposition; (4) a reduction of monocyte chemoattractant protein 1 and transforming growth factor-beta 1 activation; (5) a diminution in the activity of the profibrogenic signaling molecule SMAD-2/3 phosphorylation; (6) inhibition of proendothelin 1 activation; and (7) downregulation of expression of ets-1. Acute exposure of cultured vascular smooth muscle cells in vitro to proendothelin 1 increased both the transcription and translation of ets-1, and these effects were markedly reduced by MMP inhibition. Furthermore, infection of vascular smooth muscle cells with an adenovirus harboring a full-length ets-1 cDNA increased activities of both transforming growth factor-beta 1 and monocyte chemoattractant protein 1. Collectively, our results indicate that MMP inhibition retards age-associated arterial proinflammatory signaling, and this is accompanied by preservation of intact elastin fibers, a reduction in collagen, and blunting of an age-associated increase in blood pressure. (Hypertension. 2012;60:459-466.) circle Online Data Supplement
C1 [Wang, Mingyi; Zhang, Jing; Telljohann, Richard; Jiang, Liqun; Wu, James; Monticone, Robert E.; Kapoor, Kapil; Talan, Mark; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wang, MY (reprint author), NIA, Lab Cardiovasc Sci, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21030 USA.
EM mingyiw@grc.nia.nih.gov
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 61
TC 30
Z9 32
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD AUG
PY 2012
VL 60
IS 2
BP 459
EP +
DI 10.1161/HYPERTENSIONAHA.112.191270
PG 19
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 975ZS
UT WOS:000306550900039
PM 22689745
ER
PT J
AU Briggs, JP
Killen, J
AF Briggs, Josephine P.
Killen, Jack
TI Complementary Health Practices
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Briggs, Josephine P.; Killen, Jack] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
RP Briggs, JP (reprint author), Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
EM briggsj@mail.nih.gov
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
NR 5
TC 0
Z9 0
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 1
PY 2012
VL 308
IS 5
BP 452
EP 453
DI 10.1001/jama.2012.8161
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 981DQ
UT WOS:000306947400014
PM 22851103
ER
PT J
AU Ferrer, RA
Klein, WMP
Zajac, LE
Land, SR
Ling, BS
AF Ferrer, Rebecca A.
Klein, William M. P.
Zajac, Laura E.
Land, Stephanie R.
Ling, Bruce S.
TI An affective booster moderates the effect of gain- and loss-framed
messages on behavioral intentions for colorectal cancer screening
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Message framing; Anticipated emotion; Anticipatory emotion; Colorectal
cancer screening
ID RISK PERCEPTIONS; HEALTH BEHAVIOR; ANTICIPATED REGRET; DECISION-MAKING;
INFLUENZA VACCINATION; FEAR APPEALS; BREAST; WORRY; MAMMOGRAPHY;
PREVENTION
AB Previous research has demonstrated that loss-framed messages are more effective than gain-framed messages in motivating detection behaviors such as screening. The present study examined whether affective context moderates the degree to which message frame is associated with behavioral intentions to engage in colorectal cancer screening. In particular, we buttressed a framing manipulation with an "affective booster" to increase anticipated and anticipatory emotions associated with the framed messages. Consistent with previous research, we found that loss-framed messages are more effective in increasing intentions to screen. However, we found that among individuals who received gain-framed messages (but not loss-framed messages), the affective booster increased message persuasiveness. This effect on intentions was partially mediated by self-efficacy for engaging in screening. This study indicates that in the presence of emotional boosters, loss-framed messages may lose their advantage over gain-framed messages in motivating detection behaviors, and that self-efficacy may partially explain these effects.
C1 [Ferrer, Rebecca A.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Klein, William M. P.; Zajac, Laura E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Land, Stephanie R.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Ling, Bruce S.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4083, Rockville, MD 20852 USA.
EM ferrerra@mail.nih.gov
NR 63
TC 8
Z9 8
U1 4
U2 27
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
J9 J BEHAV MED
JI J. Behav. Med.
PD AUG
PY 2012
VL 35
IS 4
BP 452
EP 461
DI 10.1007/s10865-011-9371-3
PG 10
WC Psychology, Clinical
SC Psychology
GA 974KS
UT WOS:000306434500009
PM 21850516
ER
PT J
AU Yadav, MC
de Oliveira, RC
Foster, BL
Fong, HS
Cory, E
Narisawa, S
Sah, RL
Somerman, M
Whyte, MP
Millan, JL
AF Yadav, Manisha C.
de Oliveira, Rodrigo Cardoso
Foster, Brian L.
Fong, Hanson
Cory, Esther
Narisawa, Sonoko
Sah, Robert L.
Somerman, Martha
Whyte, Michael P.
Millan, Jose Luis
TI Enzyme replacement prevents enamel defects in hypophosphatasia mice
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE METABOLIC BONE DISEASE; TEETH AND DENTAL APPLICATIONS; TREATMENTS
ID NONSPECIFIC ALKALINE-PHOSPHATASE; IN-VITRO; INFANTILE HYPOPHOSPHATASIA;
MURINE HYPOPHOSPHATASIA; PERIODONTAL-LIGAMENT; CEMENTUM FORMATION;
AMELOBLASTIN GENE; TISSUE; MATRIX; TEETH
AB Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity, leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl-/-, aka Akp2-/-) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl-/- mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl-/- mice, histological, mu CT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP at 8.2?mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. (C) 2012 American Society for Bone and Mineral Research.
C1 [Yadav, Manisha C.; de Oliveira, Rodrigo Cardoso; Narisawa, Sonoko; Millan, Jose Luis] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA.
[de Oliveira, Rodrigo Cardoso] Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Bauru, SP, Brazil.
[Foster, Brian L.; Somerman, Martha] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
[Fong, Hanson] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Cory, Esther; Sah, Robert L.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Whyte, Michael P.] Shriners Hosp Children, St Louis, MO USA.
[Whyte, Michael P.] Washington Univ, St Louis, MO USA.
RP Millan, JL (reprint author), Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM millan@sanfordburnham.org
RI Oliveira, Rodrigo/E-2551-2012; Foster, Brian/H-8375-2015
OI Oliveira, Rodrigo/0000-0003-3070-5960; Foster, Brian/0000-0003-3444-0576
FU National Institutes of Health, USA [DE12889, AR47908, AR53102]; CAPES
[4176-09-0]
FX This work was funded by grants DE12889, AR47908, and AR53102 from the
National Institutes of Health, USA. RCO was a recipient of a fellowship
from CAPES (4176-09-0).
NR 68
TC 31
Z9 31
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD AUG
PY 2012
VL 27
IS 8
BP 1722
EP 1734
DI 10.1002/jbmr.1619
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 974XQ
UT WOS:000306471300011
PM 22461224
ER
PT J
AU Gafni, RI
Brahim, JS
Andreopoulou, P
Bhattacharyya, N
Kelly, MH
Brillante, BA
Reynolds, JC
Zhou, H
Dempster, DW
Collins, MT
AF Gafni, Rachel I.
Brahim, Jaime S.
Andreopoulou, Panagiota
Bhattacharyya, Nisan
Kelly, Marilyn H.
Brillante, Beth A.
Reynolds, James C.
Zhou, Hua
Dempster, David W.
Collins, Michael T.
TI Daily parathyroid hormone 1-34 replacement therapy for
hypoparathyroidism induces marked changes in bone turnover and structure
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE PTH; HYPOPARATHYROIDISM; HISTOMORPHOMETRY
ID MINERAL DENSITY; POSTMENOPAUSAL WOMEN; OSTEOPOROTIC WOMEN; GROWING
CHILDREN; CORTICAL BONE; ILIAC CREST; HISTOMORPHOMETRY; PTH(1-84);
CALCIUM; TRIAL
AB Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic and leads to osteoporosis; yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated 5 hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected two to three times daily for 18 months, with doses individualized to maintain serum calcium at 1.9 to 2.25?mmol/L. Biochemical markers and bone mineral density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged; however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased; however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone. Published 2012 American Society for Bone and Mineral Research. This article is a US Government work and, as such, is in the public domain in the United States of America.
C1 [Gafni, Rachel I.; Bhattacharyya, Nisan; Kelly, Marilyn H.; Brillante, Beth A.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Brahim, Jaime S.] Univ Maryland, Med Ctr, Div Oral Maxillofacial Surg, Baltimore, MD 21201 USA.
[Andreopoulou, Panagiota] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Endocrinol, Bronx, NY 10467 USA.
[Reynolds, James C.] NIH, Div Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
[Zhou, Hua; Dempster, David W.] Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA.
RP Gafni, RI (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 228,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA.
EM gafnir@mail.nih.gov
FU Division of Intramural Research at the National Institute of Dental and
Craniofacial Research, IRP, National Institutes of Health, DHHS
FX This research was supported by the Division of Intramural Research at
the National Institute of Dental and Craniofacial Research, IRP,
National Institutes of Health, DHHS.
NR 31
TC 21
Z9 25
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD AUG
PY 2012
VL 27
IS 8
BP 1811
EP 1820
DI 10.1002/jbmr.1627
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 974XQ
UT WOS:000306471300019
PM 22492501
ER
PT J
AU Ibrahim, L
DiazGranados, N
Jolkovsky, L
Brutsche, N
Luckenbaugh, DA
Herring, WJ
Potter, WZ
Zarate, CA
AF Ibrahim, Lobna
DiazGranados, Nancy
Jolkovsky, Libby
Brutsche, Nancy
Luckenbaugh, David A.
Herring, W. Joseph
Potter, William Z.
Zarate, Carlos A., Jr.
TI A Randomized, Placebo-Controlled, Crossover Pilot Trial of the Oral
Selective NR2B Antagonist MK-0657 in Patients With Treatment-Resistant
Major Depressive Disorder
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE depression; glutamate; NMDA; NR2B; treatment
ID D-ASPARTATE ANTAGONIST; RATING-SCALE; NMDA RECEPTOR; STATES; KETAMINE
AB Converging lines of evidence suggest that the glutamatergic system may play an increasingly important role in the development of novel therapeutics for major depressive disorder (MDD), particularly agents associated with rapid antidepressant effects. Diverse glutamatergic modulators targeting N-methyl-D-aspartate receptors have shown efficacy in MDD, but their associated psychotomimetic effects presently preclude their use in larger samples. This small, randomized, double-blind, placebo-controlled, crossover pilot study evaluated the potential antidepressant efficacy and tolerability of an oral formulation of the selective N-methyl-D-aspartate NR2B antagonist MK-0657 in patients with treatment-resistant MDD (TRD). The TRD subjects underwent a 1-week drug-free period and were subsequently randomized to receive either MK-0657 monotherapy (4-8 mg/d) or placebo for 12 days. Because of recruitment challenges and the discontinuation of the compound's development by the manufacturer, only 5 of the planned 21 patients completed both periods of the crossover administration of MK-0657 and placebo. Significant antidepressant effects were observed as early as day 5 in patients receiving MK-0657 compared with those receiving placebo, as assessed by the Hamilton Depression Rating Scale and Beck Depression Inventory; however, no improvement was noted when symptoms were assessed with the Montgomery-Asberg Depression Rating Scale, the primary efficacy measure. No serious or dissociative adverse effects were observed in patients receiving this oral formulation of MK-0657. Despite the small sample size, this pilot study suggests that an oral formulation of the NR2B antagonist MK-0657 may have antidepressant properties in TRD patients. Further studies with larger sample sizes are necessary to confirm these preliminary findings.
C1 [Zarate, Carlos A., Jr.] NIMH, CRC, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[DiazGranados, Nancy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Herring, W. Joseph] Merck Res Labs, Clin Neurosci, N Wales, PA USA.
[Potter, William Z.] Merck Res Labs, Translat Neurosci, N Wales, PA USA.
RP Zarate, CA (reprint author), NIMH, CRC, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program,NIH, 10 Ctr Dr,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health; Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
Department of Health & Human Services (IRP-NIMH-NIH-DHHS); US government
FX The authors acknowledge the support of the Intramural Research Program
of the National Institute of Mental Health, National Institutes of
Health, and Department of Health & Human Services (IRP-NIMH-NIH-DHHS).
The authors thank the 7SE research unit and research staff for their
support, Ioline Henter for her outstanding editorial assistance in the
preparation of this manuscript, and Kerry Budd for her assistance in
materials transfer to help support the project.; Dr Zarate is listed as
a co-inventor on a patent for the use of ketamine in major depression.
Dr Zarate has assigned his patent rights on ketamine and its metabolites
to the US government but will share a percentage of any royalties that
may be received by the government. Dr Herring is an employee of Merck
Sharp and Dohme Corp. and holds stock and stock options in the company.
This work was initiated when Dr Potter was an employee of Merck Sharp
and Dohme Corp; he has since retired but continues to hold stock in the
company.
NR 35
TC 66
Z9 68
U1 5
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD AUG
PY 2012
VL 32
IS 4
BP 551
EP 557
DI 10.1097/JCP.0b013e31825d70d6
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 970GE
UT WOS:000306115300017
PM 22722512
ER
PT J
AU Grolla, A
Mehedi, M
Lindsay, R
Bosio, C
Duse, A
Feldmann, H
AF Grolla, Allen
Mehedi, Masfique
Lindsay, Robbin
Bosio, Catharine
Duse, Adriano
Feldmann, Heinz
TI Enhanced detection of Rift Valley fever virus using molecular assays on
whole blood samples
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Article
DE Rift Valley fever virus; Macrophage; qRT PCR; Diagnostics; Whole blood
ID EGYPT 1977-78; PCR; OUTBREAK; CULTURES; KENYA
AB Background: Rift Valley fever (RVF) is an emerging arthropod-borne zoonoses of global agricultural and public health importance. In December 2006, an RVF outbreak was recognized in Kenya which led to the deployment of international response laboratory teams to the area.
Objectives: A field laboratory was operated in Malindi, Kenya to provide safe sample handling and molecular testing for RVF virus (RVFV) as well as selected other pathogens for differential diagnosis.
Study design: Safe sample handling was carried out using a negative pressure flexible film isolator (glovebox) and commercial reagents to inactivate clinical specimens and purify nucleic acid. Whole blood was routinely used for diagnostic testing although paired plasma samples were also tested in select cases. Subsequently, human macrophages were tested in vitro for their susceptibility to RVFV.
Results: The field laboratory received samples from 33 individuals and a definite laboratory diagnosis was provided in 16 of these cases. Using molecular diagnostic techniques, RVFV was more consistently detected in whole blood than in plasma samples most likely due to association of RVFV with blood cells. Subsequent in vitro studies identified macrophages as a target cell for RVFV replication.
Conclusions: RVFV appears to replicate in blood cells such as macrophages. Thus, the sensitivity of molecular diagnostic testing is improved if whole blood is used as the clinical specimen rather than plasma or serum. Published by Elsevier B.V.
C1 [Mehedi, Masfique; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Grolla, Allen; Lindsay, Robbin; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Mehedi, Masfique; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Bosio, Catharine] NIAID, Intracellular Parasites Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Duse, Adriano] Univ Witwatersrand, Dept Clin Microbiol & Infect Dis, Johannesburg, South Africa.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
EM feldmannh@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015; Mehedi, masfique/J-6618-2014
OI Mehedi, masfique/0000-0003-1728-3126
FU World Health organization; National Microbiology Laboratory of the
Public Health Agency of Canada; Intramural Research Program of the
National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Ministry of Health, Nairobi, Kenya; World Health
Organization, Kenya Country Office, Nairobi, Kenya; World Health
Organization Geneva, Switzerland; Malindi District Hospital, Malindi,
Kenya; Kenya Medical Research Institute, Nairobi, Kenya; Center for
Disease Control and Prevention, Nairobi, Kenya; Center for Disease
Control and Prevention, Atlanta, USA; Center for Disease Control and
Prevention, Fort Collins, USA; Institute of Tropical and Infectious
Diseases; University of Nairobi, Nairobi, Kenya; National Institute of
Communicable Diseases, Sandringham, South Africa
FX The field component of this work was funded by the World Health
organization and the National Microbiology Laboratory of the Public
Health Agency of Canada while the studies on in vitro infection of human
macrophages was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.; The Mobile Laboratory Unit was supported by the
National Microbiology Laboratory of the Public Health Agency of Canada.
The outbreak response mission was supported by the World Health
Organization. The authors would like to thank the following
agencies/institutions for their support and assistance: Ministry of
Health, Nairobi, Kenya; World Health Organization, Kenya Country Office,
Nairobi, Kenya, and Geneva, Switzerland; Malindi District Hospital,
Malindi, Kenya; Kenya Medical Research Institute, Nairobi, Kenya;
Centers for Disease Control and Prevention, Nairobi, Kenya, Atlanta,
USA, Fort Collins, USA; Institute of Tropical and Infectious Diseases,
University of Nairobi, Nairobi, Kenya; National Institute of
Communicable Diseases, Sandringham, South Africa. The authors are
grateful to local hospital and public health staff for their help and
support. We highly appreciate the collaboration by the patients and
their family members as well as the communities. We also would like to
thank Anita Mora (Division of Intramural Research, NIAID, NIH) for
assistance with the graphical work.
NR 22
TC 6
Z9 6
U1 3
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
J9 J CLIN VIROL
JI J. Clin. Virol.
PD AUG
PY 2012
VL 54
IS 4
BP 313
EP 317
DI 10.1016/j.jcv.2012.04.022
PG 5
WC Virology
SC Virology
GA 973QK
UT WOS:000306374700005
PM 22632901
ER
PT J
AU Yoon, IK
Rothman, AL
Tannitisupawong, D
Srikiatkhachorn, A
Jarman, RG
Aldstadt, J
Nisalak, A
Mammen, MP
Thammapalo, S
Green, S
Libraty, DH
Gibbons, RV
Getis, A
Endy, T
Jones, JW
Koenraadt, CJM
Morrison, AC
Fansiri, T
Pimgate, C
Scott, TW
AF Yoon, In-Kyu
Rothman, Alan L.
Tannitisupawong, Darunee
Srikiatkhachorn, Anon
Jarman, Richard G.
Aldstadt, Jared
Nisalak, Ananda
Mammen, Mammen P., Jr.
Thammapalo, Suwich
Green, Sharone
Libraty, Daniel H.
Gibbons, Robert V.
Getis, Arthur
Endy, Timothy
Jones, James W.
Koenraadt, Constantianus J. M.
Morrison, Amy C.
Fansiri, Thanyalak
Pimgate, Chusak
Scott, Thomas W.
TI Underrecognized Mildly Symptomatic Viremic Dengue Virus Infections in
Rural Thai Schools and Villages
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID KAMPHAENG PHET; AEDES-AEGYPTI; TRANSMISSION; CHILDREN; EPIDEMIOLOGY;
BLOOD; SURVEILLANCE; INAPPARENT; INDONESIA; PATTERNS
AB Background. The understanding of dengue virus (DENV) transmission dynamics and the clinical spectrum of infection are critical to informing surveillance and control measures. Geographic cluster studies can elucidate these features in greater detail than cohort studies alone.
Methods. A 4-year longitudinal cohort and geographic cluster study was undertaken in rural Thailand. Cohort children underwent pre-/postseason serology and active school absence-based surveillance to detect inapparent and symptomatic dengue. Cluster investigations were triggered by cohort dengue and non-dengue febrile illnesses (positive and negative clusters, respectively).
Results. The annual cohort incidence of symptomatic dengue ranged from 1.3% to 4.4%. DENV-4 predominated in the first 2 years, DENV-1 in the second 2 years. The inapparent-to-symptomatic infection ratio ranged from 1.1:1 to 2.9:1. Positive clusters had a 16.0% infection rate, negative clusters 1.1%. Of 119 infections in positive clusters, 59.7% were febrile, 20.2% were afebrile with other symptoms, and 20.2% were asymptomatic. Of 16 febrile children detected during cluster investigations who continued to attend school, 9 had detectable viremia.
Conclusions. Dengue transmission risk was high near viremic children in both high- and low-incidence years. Inapparent infections in the cohort overestimated the rate of asymptomatic infections. Ambulatory children with mild febrile viremic infections could represent an important component of dengue transmission.
C1 [Yoon, In-Kyu; Tannitisupawong, Darunee; Jarman, Richard G.; Nisalak, Ananda; Mammen, Mammen P., Jr.; Gibbons, Robert V.; Pimgate, Chusak] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
[Rothman, Alan L.] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA.
[Srikiatkhachorn, Anon; Green, Sharone; Libraty, Daniel H.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
[Aldstadt, Jared] SUNY Buffalo, Dept Geog, Buffalo, NY 14260 USA.
[Thammapalo, Suwich] Thailand Minist Publ Hlth, Dept Dis Control, Bur Vector Borne Dis, Nonthaburi, Thailand.
[Getis, Arthur] San Diego State Univ, Dept Geog, San Diego, CA 92182 USA.
[Endy, Timothy] SUNY Syracuse, Dept Infect Dis, Syracuse, NY USA.
[Jones, James W.; Fansiri, Thanyalak] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand.
[Koenraadt, Constantianus J. M.] Wageningen Univ, Entomol Lab, Wageningen, Netherlands.
[Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Scott, Thomas W.] Fogarty Int Ctr, NIH, Bethesda, MD USA.
RP Yoon, IK (reprint author), USAMC AFRIMS, APO, AP 96546 USA.
EM yooni@afrims.org
RI Aldstadt, Jared/A-8508-2009
OI Aldstadt, Jared/0000-0001-9162-7439
FU US National Institutes of Health [P01 AI34533, R01 GM083224]; US
Military Infectious Diseases Research Program [S0016-04-AF]; Bill &
Melinda Gates Foundation Global Health Program [OPP52250]
FX This work was supported by the US National Institutes of Health (grant
numbers P01 AI34533 and R01 GM083224); the US Military Infectious
Diseases Research Program (grant number S0016-04-AF); and the Bill &
Melinda Gates Foundation Global Health Program (grant number OPP52250).
NR 30
TC 44
Z9 44
U1 1
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2012
VL 206
IS 3
BP 389
EP 398
DI 10.1093/infdis/jis357
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 973OI
UT WOS:000306369100012
PM 22615312
ER
PT J
AU Flynn, PM
Nachman, S
Muresan, P
Fenton, T
Spector, SA
Cunningham, CK
Pass, R
Yogev, R
Burchett, S
Heckman, B
Bloom, A
Utech, LJ
Anthony, P
Petzold, E
Levy, W
Siberry, GK
Ebiasah, R
Miller, J
Handelsman, E
Weinberg, A
AF Flynn, Patricia M.
Nachman, Sharon
Muresan, Petronella
Fenton, Terence
Spector, Stephen A.
Cunningham, Coleen K.
Pass, Robert
Yogev, Ram
Burchett, Sandra
Heckman, Barbara
Bloom, Anthony
Utech, L. Jill
Anthony, Patricia
Petzold, Elizabeth
Levy, Wende
Siberry, George K.
Ebiasah, Ruth
Miller, Judi
Handelsman, Edward
Weinberg, Adriana
CA IMPAACT P1088 Team
TI Safety and Immunogenicity of 2009 Pandemic H1N1 Influenza Vaccination in
Perinatally HIV-1-Infected Children, Adolescents, and Young Adults
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; EVENT REPORTING
SYSTEM; ANTIBODY-RESPONSES; ANTIRETROVIRAL THERAPY; A/H1N1 VACCINE;
UNITED-STATES; SPLIT VIRION; DOUBLE-BLIND; OPEN-LABEL
AB Background. The safety and immunogenicity of high-dose pandemic H1N1 (pH1N1) vaccination in perinatally human immunodeficiency virus type 1 (HIV-1)-infected children, adolescents, and young adults are unknown.
Methods. Two 30-mu g doses of 2009 Novartis pH1N1 monovalent vaccine (Fluvirin) were administered 21-28 days apart to perinatally HIV-1-infected children, adolescents, and young adults. Antibodies were measured by hemagglutination inhibition (HAI) assay at baseline, 21-28 days after first vaccination, 7-13 days after the second vaccination, and 7 months after the first vaccination.
Results. Among the 155 participants, 54 were aged 4-8 years, 51 were aged 9-17 years, and 50 were aged 18-24 years. After 2 doses of Fluvirin, seroresponse (>= 4-fold rise in HAI titers) was demonstrated in 79.6%, 84.8%, and 83% of participants in the aforementioned age groups, respectively, and seroprotection (HAI titers >= 40) was shown in 79.6%, 82.6%, and 85.1%, respectively. Of those lacking seroresponse (n = 43) or seroprotection (n = 37) after the first vaccination, 46.5% and 40.5% achieved seroresponse or seroprotection, respectively, after the second vaccination. Among participants who lacked seroprotection at entry, a "complete response" (both seroresponse and seroprotection) after first vaccination was associated with higher baseline log(10) HAI titer and non-Hispanic ethnicity. No serious vaccine-related events occurred.
Conclusion. Two doses of double-strength pH1N1 vaccine are safe and immunogenic and may provide improved protection against influenza in perinatally HIV-1-infected children and youth.
C1 [Flynn, Patricia M.; Utech, L. Jill] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Nachman, Sharon] SUNY Stony Brook, Hlth Sci Ctr, Stony Brook, NY USA.
[Muresan, Petronella; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Spector, Stephen A.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA USA.
[Cunningham, Coleen K.] Duke Univ, Med Ctr, Durham, NC USA.
[Pass, Robert] Univ Alabama Birmingham, Birmingham, AL USA.
[Yogev, Ram] Northwestern Univ, Sch Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Yogev, Ram] Northwestern Univ, Sch Med, Childrens Mem Hosp, Chicago, IL 60611 USA.
[Burchett, Sandra] Childrens Hosp Boston, Boston, MA USA.
[Heckman, Barbara; Bloom, Anthony] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA.
[Anthony, Patricia] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Petzold, Elizabeth; Levy, Wende] Social & Sci Syst, Silver Spring, MD USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Ebiasah, Ruth; Miller, Judi; Handelsman, Edward] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Weinberg, Adriana] Univ Colorado Denver, Aurora, CO USA.
RP Flynn, PM (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 262 Danny Thomas Pl,Mailstop 600, Memphis, TN 38105 USA.
EM pat.flynn@st.jude.org
FU HIV Program NICHD CRS (CTSI) [U54 RR025771]; 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 [AI068632]; Statistical and
Data Analysis Center at the Harvard School of Public Health under the
National Institute of Allergy and Infectious Diseases (Pediatric AIDS
Clinical Trials Group and IMPAACT group) [5 U01 AI41110, 1 U01
AI068616]; NICHD [N01-DK-9-001/HHSN267200800001C]
FX We thank the participating sites and site personnel: 60422: St
Jude/Memphis IMPAACT Clinical Trials Unit [CTU] (Nehali Patel, MD;
Sandra Boyd, RN, MSN, PNP; Tom Wride, MS; Aditya Gaur, MD); 60402: The
Children's Hospital of Philadelphia International Maternal Pediatric
Adolescent AIDS CTU (Steven D. Douglas, MD; Richard M. Rutstein, MD;
Carol A. Vincent, CRNP, MSN; Margaret R. Duckett, RN, BSN); 60318: UCSD
IMPAACT CTU (Rolando Viani, MD, MTP; Lisa Stangl, NP; Jeanne Manning,
RN; Kimberly Norris, RN); 60336: Baylor College of Medicine CTU (Norma
Cooper, MA, RN, BSN, ACRN; Mary Paul, MD, Kathleen Pitts, CPNP; Terry
Raburn, RN); 60444: Bronx-Lebanon Hospital Family Center CTU (Seema
Chittalae, MD; Mavis Dummitt, RN; Stefan Hagmann, MD; Murli Purswani,
MD); 5031 San Juan City Hospital PR NICHD Clinical Research Site [CRS]
(Midnela Acevedo-Flores, MD; Wanda I. Marrero, BSN, RN; Lizbeth
Fabregas, BS, MS; Mario Paulino, MD); 5041: Children's Hospital of
Michigan NICHD CRS (Chokechai Rongkavilit, MD; Ellen Moore, MD; Ulyssa
Hancock, MSN, RN, PNP; Ayanna Walters, RN); 60325: Duke University
Medical Center HIV/AIDS CTU (Joan Wilson, John Swetnam, Margaret
Donnelly, Mary Jo Hassett); 60341: Columbia Collaborative-HIV/AIDS CTU;
2802 New Jersey Medical School CRS; 60466: UCLA-Los Angeles/Brazil AIDS
Consortium CTU; 60349: University of Miami Pediatric Perinatal HIV/AIDS
CTU (Gwendolyn B. Scott, MD; Charles D. Mitchell, MD; Patricia Bryant,
RN, BSN; Claudia Florez, MD); 5013: Jacobi Medical Center Bronx NICHD
CRS (Joanna Dobroszycki, MD; Marlene Burey, RN, MSHS, CPN; Raphaelle
Auguste, RN, BSN; Karen Kassen, RN); 5017: Seattle Children's Hospital
CRS (Ann J. Melvin, MD, MPH; Joycelyn Thomas, RN; Corry Venema-Weiss,
ARNP; Lisa M Frenkel, MD); 5040: SUNY Stony Brook NICHD CRS (Denise
Ferraro, FNP; Michele Kelly, NP; Erin Infanzon); 60323: WNE Maternal
Pediatric Adolescent AIDS CTU; 60339: Children's Memorial
Hospital-Chicago; 60446: University of Puerto Rico CTU (Carmen D.
Zorrilla, MD; Irma Febo, MD; Vivian Tamayo-Agrait, MD; Ruth
Santos-Otero, RN); 5015: Children's National Medical Center Washington
DC NICHD CRS (Steven Zeichner, MD, PhD; Deidre Thompson, RN; Chrisa
Thomas, BA); 5018: University of South Florida-Tampa NICHD CRS (Jorge
Lujan-Zilberman, MD; Patricia Emmanuel, MD; Denise Casey, RN; Tammy
Myers); 5009: Children's Hospital of Boston NICHD CRS (Charlotte Mao,
MD, MPH; Catherine Kneut, RN, CPNP; Nancy Karthas, RN, CPN); 5012: New
York University NY NICHD CRS (Sandra Deygoo, MS; Siham Akleh, RN; Aditya
Kaul, MD; William Borkowsky, MD; CTSI grant: 1UL1RR029893); 5003:
Metropolitan Hospital NICHD CRS; 5011: Boston Medical Center Pediatrics.
HIV Program NICHD CRS (Ellen R. Cooper, MD; Debra McLaud, RN, Diana
Clarke, Pharm D, CTSI grant: U54 RR025771).; Overall support for the
IMPAACT group 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 (AI068632). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. This
work was supported by the Statistical and Data Analysis Center at the
Harvard School of Public Health, under the National Institute of Allergy
and Infectious Diseases (cooperative agreement number 5 U01 AI41110 with
the Pediatric AIDS Clinical Trials Group and number 1 U01 AI068616 with
the IMPAACT group). Support of the sites was provided by the NIAID and
the NICHD International and Domestic Pediatric and Maternal HIV Clinical
Trials Network funded by NICHD (contract number
N01-DK-9-001/HHSN267200800001C).
NR 50
TC 11
Z9 11
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2012
VL 206
IS 3
BP 421
EP 430
DI 10.1093/infdis/jis360
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 973OI
UT WOS:000306369100016
PM 22615311
ER
PT J
AU Kim, SM
Romero, R
Lee, J
Lee, SM
Park, CW
Park, JS
Yoon, BH
AF Kim, Sun Min
Romero, Roberto
Lee, JoonHo
Lee, Seung Mi
Park, Chan-Wook
Park, Joong Shin
Yoon, Bo Hyun
TI The frequency and clinical significance of intra-amniotic inflammation
in women with preterm uterine contractility but without cervical change:
do the diagnostic criteria for preterm labor need to be changed?
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Funisitis; histologic chorioamnionitis; microorganisms; MMP-8;
prematurity; preterm birth; preterm delivery; preterm parturition
ID AMNIOTIC-FLUID INTERLEUKIN-6; NECROSIS-FACTOR-ALPHA; BLOOD-CELL COUNT;
POLYMERASE-CHAIN-REACTION; C-REACTIVE PROTEIN; MIDTRIMESTER GENETIC
AMNIOCENTESIS; PREMATURE RUPTURE; MICROBIAL INVASION; INTACT MEMBRANES;
INTRAUTERINE INFECTION
AB Objective: The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. Methods: Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). Results: (1) Intra-amniotic inflammation was present in 12.1% (16/132); (2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and (3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < 0.05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. Conclusion: Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes.
C1 [Kim, Sun Min; Lee, JoonHo; Lee, Seung Mi; Park, Chan-Wook; Park, Joong Shin; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, 28 Yeongeon Dong, Seoul 110744, South Korea.
EM yoonbh@snu.ac.kr
RI Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012;
OI Park, Joong Shin/0000-0002-5246-0477
FU National Research Foundation of Korea (NRF); Korea government (MEST)
[2011-0000195]; Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS
FX This study was supported (by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (No. 2011-0000195) and
in part) by the Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS.
NR 187
TC 15
Z9 15
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD AUG
PY 2012
VL 25
IS 8
BP 1212
EP 1221
DI 10.3109/14767058.2011.629256
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 974MM
UT WOS:000306439600003
PM 21999173
ER
PT J
AU Fejzo, MS
Ching, CY
Schoenberg, FP
Macgibbon, K
Romero, R
Goodwin, TM
Mullin, PM
AF Fejzo, Marlena S.
Ching, ChunYu
Schoenberg, Frederic P.
Macgibbon, Kimber
Romero, Roberto
Goodwin, T. Murphy
Mullin, Patrick M.
TI Change in paternity and recurrence of hyperemesis gravidarum
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE genetic; nausea; paternal; pregnancy
ID EARLY-PREGNANCY; WERNICKES ENCEPHALOPATHY; THYROTROPIN RECEPTOR; LARGE
COHORT; NAUSEA; OUTCOMES; RISK; EPIDEMIOLOGY; POPULATION; SYMPTOMS
AB Objective: To determine whether change in paternity changes recurrence risk of hyperemesis gravidarum (HG). Study design: Survey data on recurrence of HG was compared between cases who had a paternity change between pregnancies and cases who did not. Results: The percentage of HG pregnancies in women with the same partner for all pregnancies was not significantly different from the percentage of HG pregnancies in women who changed partners for at least one pregnancy (78% vs 71%, p > 0.05). Participants who did and did not change partners between their first and second pregnancies, were asked to rate their first and second pregnancy in regards to symptoms of HG. Neither the ratings nor the change in rating between pregnancies was significantly different between the two groups. Conclusion: Women reported HG in over 70% of their pregnancies regardless of a paternity change. Paternal genes expressed through the fetus do not have a significant effect on incidence or recurrence of HG. This study supports a strong maternal genetic factor involved in HG. However, because the recurrence risk is not 100%, other factors play a role. Identification of the predisposing gene(s) and other factors will determine the cause of this poorly understood complication of pregnancy.
C1 [Fejzo, Marlena S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Fejzo, Marlena S.; Goodwin, T. Murphy; Mullin, Patrick M.] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90033 USA.
[Ching, ChunYu; Schoenberg, Frederic P.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA.
[Macgibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
RP Fejzo, MS (reprint author), Univ Calif Los Angeles, Dept Med, 5535 MRL BLDG,675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported (in part) by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 40
TC 2
Z9 2
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD AUG
PY 2012
VL 25
IS 8
BP 1241
EP 1245
DI 10.3109/14767058.2011.632039
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 974MM
UT WOS:000306439600007
PM 22010839
ER
PT J
AU Wang, A
Holston, AM
Yu, KF
Zhang, J
Toporsian, M
Karumanchi, SA
Levine, RJ
AF Wang, Alice
Holston, Alexander M.
Yu, Kai F.
Zhang, Jun
Toporsian, Mourad
Karumanchi, S. Ananth
Levine, Richard J.
TI Circulating anti-angiogenic factors during hypertensive pregnancy and
increased risk of respiratory distress syndrome in preterm neonates
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Anti-angiogenic; soluble fms-like tyrosine kinase 1; sVEGF R1; sFlt1;
placental growth factor; PlGF; soluble endoglin; sEng; respiratory
distress syndrome; RDS; neonate; preterm; preeclampsia; gestational
hypertension
ID ENDOTHELIAL GROWTH-FACTOR; GESTATIONAL HYPERTENSION; SOLUBLE ENDOGLIN;
UNITED-STATES; PREECLAMPSIA; OUTCOMES; BIRTH; LUNG; INHIBITION;
DIAGNOSIS
AB Objective: To test the hypothesis that high circulating concentrations of maternal anti-angiogenic factors are associated with increased risk of respiratory distress syndrome (RDS). Study Design: This is a nested case-control study of nulliparous women who delivered less than 37 weeks of gestation within the Calcium for Preeclampsia Prevention (CPEP) trial. The study included 116 women with preeclampsia or gestational hypertension and 323 normotensive controls. Soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in maternal serum were measured at 21-32 weeks of gestation. Results: Preterm infants born to hypertensive mothers were more likely to develop RDS (22.5% vs. 20.9%, p = 0.03). After adjustment for gestational age at delivery, the odds ratio for the relationship between hypertension in pregnancy and RDS was 2.18 (95% CI 1.08-4.39). In hypertensive pregnancies women whose infants developed RDS had significantly higher circulating mean sFlt1 levels during midpregnancy (21-32 weeks of gestation) even after adjustment for gestational age at delivery (21,516 pg/mL vs. 7,000 pg/mL, p = 0.01). Conclusions: Preterm preeclampsia and gestational hypertension, characterized by high circulating levels of sFlt1, are associated with a twofold increased risk of RDS in infants delivered before 37 weeks. Among women with these hypertensive pregnancies circulating sFlt1 concentrations during midpregnancy were substantially higher in women whose infants developed RDS.
C1 [Wang, Alice; Toporsian, Mourad; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Toporsian, Mourad] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA.
[Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Alice] Boston Univ, Boston Med Ctr, Dept Pediat, Boston, MA 02215 USA.
[Holston, Alexander M.] USN, Dept Pediat, Med Ctr Portsmouth, Portsmouth, Hants, England.
[Yu, Kai F.] Tsinghua Univ, Dept Math Sci, Beijing 100084, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China.
[Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
EM sananth@bidmc.harvard.edu
OI Wang, Alice/0000-0002-5153-0365; Toporsian, Mourad/0000-0002-8430-2094
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, US Department of Health and
Human Services; Howard Hughes Medical Institute; Flight Attendant
Medical Research Institute
FX This study was supported by the intramural research program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, US Department of Health and
Human Services to R.J.L; and by the Howard Hughes Medical Institute to
S. A. K. Dr. Wang receives funding from the Flight Attendant Medical
Research Institute.
NR 33
TC 13
Z9 13
U1 0
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD AUG
PY 2012
VL 25
IS 8
BP 1447
EP 1452
DI 10.3109/14767058.2011.640368
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 974MM
UT WOS:000306439600051
PM 22097923
ER
PT J
AU Sherer, EA
Sale, ME
Pollock, BG
Belani, CP
Egorin, MJ
Ivy, PS
Lieberman, JA
Manuck, SB
Marder, SR
Muldoon, MF
Scher, HI
Solit, DB
Bies, RR
AF Sherer, Eric A.
Sale, Mark E.
Pollock, Bruce G.
Belani, Chandra P.
Egorin, Merrill J.
Ivy, Percy S.
Lieberman, Jeffrey A.
Manuck, Stephen B.
Marder, Stephen R.
Muldoon, Matthew F.
Scher, Howard I.
Solit, David B.
Bies, Robert R.
TI Application of a single-objective, hybrid genetic algorithm approach to
pharmacokinetic model building
SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
LA English
DT Article
DE Pharmacokinetics; Model building; Genetic algorithms
ID CATIE; SCHIZOPHRENIA; EXPOSURE; SMOKING; IMPACT; RACE
AB A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q (1) = 4.9 % and q (3) = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data.
C1 [Sherer, Eric A.; Sale, Mark E.; Bies, Robert R.] Indiana Univ Sch Med, Div Clin Pharmacol, Dept Med, Indianapolis, IN 46204 USA.
[Sherer, Eric A.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA.
[Sale, Mark E.] Next Level Solut, Raleigh, NC USA.
[Pollock, Bruce G.; Bies, Robert R.] Univ Toronto, Ctr Addit & Mental Hlth, Toronto, ON, Canada.
[Pollock, Bruce G.] Univ Toronto, Baycrest Hosp, Rotman Res Inst, Toronto, ON, Canada.
[Pollock, Bruce G.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA.
[Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Ivy, Percy S.] NCI, Bethesda, MD 20892 USA.
[Lieberman, Jeffrey A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Behav Physiol Lab, Pittsburgh, PA 15260 USA.
[Marder, Stephen R.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Muldoon, Matthew F.] Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA.
[Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10021 USA.
[Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
RP Bies, RR (reprint author), Indiana Univ Sch Med, Div Clin Pharmacol, Dept Med, Indianapolis, IN 46204 USA.
EM rrbies@iupui.edu
OI Belani, Chandra/0000-0001-5049-5329
FU Eli Lilly and Company through the Indiana Clinical and Translational
Sciences Institute; National Institute of Health, National Center for
Research Resources, Clinical and Translational Sciences Award [RR05761];
National Institutes of Mental Health [P01-HL-40962, K24-MH-065416,
M01-RR-000056, MH65376, MH30915, MH064173, MH076420, MH052247,
N01MH090001]
FX This project was supported by Eli Lilly and Company through the Indiana
Clinical and Translational Sciences Institute funded, in part by grant
RR05761 from the National Institute of Health, National Center for
Research Resources, Clinical and Translational Sciences Award. The
authors would also like to acknowledge financial support from National
Institutes of Mental Health grants P01-HL-40962 (citalopram),
K24-MH-065416 (citalopram, olanzapine, perphenazine, risperidone),
M01-RR-000056 (citalopram), MH65376 (escitalopram), MH30915
(escitalopram), MH064173 (olanzapine, perphenazine, risperidone, and
ziprasidone), MH076420 (olanzapine), MH052247 (perphenazine and
risperidone), N01MH090001 (perphenazine, risperidone, and ziprasidone).
The authors are grateful to Ellen Frank, Ramesh K. Ramanathan, the
investigators of the CATIE studies, and the CATIE Executive Committee of
Drs. Lieberman, Stroup, Tariot, and Schneider.
NR 24
TC 5
Z9 6
U1 1
U2 22
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1567-567X
J9 J PHARMACOKINET PHAR
JI J. Pharmacokinet. Pharmacodyn.
PD AUG
PY 2012
VL 39
IS 4
BP 393
EP 414
DI 10.1007/s10928-012-9258-0
PG 22
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 976HJ
UT WOS:000306571300007
PM 22767341
ER
PT J
AU Ghatol, A
Ruhl, AP
Danoff, SK
AF Ghatol, Abhijeet
Ruhl, A. Parker
Danoff, Sonye K.
TI Exacerbations in Idiopathic Pulmonary Fibrosis Triggered by Pulmonary
and Nonpulmonary Surgery: A Case Series and Comprehensive Review of the
Literature
SO LUNG
LA English
DT Review
DE Acute exacerbation; Idiopathic pulmonary fibrosis; Surgery; Circulating
fibrocytes
ID SURGICAL LUNG-BIOPSY; USUAL INTERSTITIAL PNEUMONIA; CIRCULATING
FIBROCYTES; CANCER; MORTALITY; RESECTION; DISEASE; RISK
AB Acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are well recognized in the progression of this uniformly fatal disease. Surgical lung biopsy and lung resection may initiate these acute events leading to a rapid deterioration and permanent decline in lung function. Our aim is to discuss the role of pulmonary and nonpulmonary surgery as a precipitating factor and to review the literature on the nature, course, and outcomes of acute exacerbations in the context of surgical interventions.
This study consisted of a retrospective case series of patients at the Johns Hopkins Hospital who experienced acute exacerbation following a surgical procedure. Patients included in the case series suffered from aggravation of dyspnea within 1 month after surgical intervention, with new infiltrates on imaging. There was no other more likely cause after diagnostic evaluation. A comprehensive review of the current literature pertaining to AEs of IPF in the context of a surgical intervention was performed.
In a series of four patients from Johns Hopkins Hospital with AE in IPF, two of three patients who underwent video-assisted thoracoscopic surgery (VATS) lung biopsy had a fatal outcome. The fourth patient survived an AE after a total knee replacement but had a fatal outcome after a subsequent coronary artery bypass graft surgery. We found no report in the literature of AE in an IPF patient who underwent nonpulmonary surgery.
Acute exacerbations of IPF can occur postoperatively after both pulmonary and nonpulmonary surgery and are associated with a high mortality rate. As a next step, a prospective multicenter clinical study of patients with IPF undergoing both pulmonary and nonpulmonary surgeries would allow the identification of perioperative risk factors in the development of AE of IPF.
C1 [Ruhl, A. Parker; Danoff, Sonye K.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
[Ghatol, Abhijeet] Cedars Sinai Med Ctr, Dept Pulm & Crit Care Med, Los Angeles, CA 90048 USA.
[Ruhl, A. Parker] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Danoff, SK (reprint author), Johns Hopkins Univ, Div Pulm & Crit Care Med, 1830 E Monument St,5th Floor, Baltimore, MD 21205 USA.
EM sdanoff@jhmi.edu
NR 26
TC 20
Z9 20
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0341-2040
J9 LUNG
JI Lung
PD AUG
PY 2012
VL 190
IS 4
BP 373
EP 380
DI 10.1007/s00408-012-9389-5
PG 8
WC Respiratory System
SC Respiratory System
GA 974LT
UT WOS:000306437600003
PM 22543997
ER
PT J
AU Maudsley, S
AF Maudsley, Stuart
TI G Protein-Coupled Receptor Biased Agonism: Development Towards Future
Selective Therapeutics
SO MINI-REVIEWS IN MEDICINAL CHEMISTRY
LA English
DT Editorial Material
C1 NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
NR 5
TC 3
Z9 3
U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-5575
J9 MINI-REV MED CHEM
JI Mini-Rev. Med. Chem.
PD AUG
PY 2012
VL 12
IS 9
BP 803
EP 803
PG 1
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 975OR
UT WOS:000306521100001
PM 22757722
ER
PT J
AU Maudsley, S
Patel, SA
Park, SS
Luttrell, LM
Martin, B
AF Maudsley, S.
Patel, S. A.
Park, S. -S.
Luttrell, L. M.
Martin, B.
TI Functional Signaling Biases in G Protein-Coupled Receptors: Game Theory
and Receptor Dynamics
SO MINI-REVIEWS IN MEDICINAL CHEMISTRY
LA English
DT Review
DE G protein-coupled receptor; biased agonist; signaling; drug design;
aging; allostasis
ID DYSTROPHIN-ASSOCIATED PROTEIN; EXCHANGER REGULATORY FACTOR;
BETA-ADRENERGIC-RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; HEART-FAILURE;
AGONIST TRAFFICKING; ANTAGONISTS PROMOTE; PARATHYROID-HORMONE;
ACTIVATION; ARRESTIN
AB Pharmacotherapeutic targeting of G protein-coupled receptors (GPCRs) is perhaps the most important field of drug design, as agents designed to control these receptors constitute more than half of the pharmacopeia. Initially GPCRs were considered to be unitary entities, possessing all of their potential functionality in their characteristic heptahelical core. Early models of the functional activity of GPCRs considered them to possess just a simple 'on' or 'off' status. Recent research however has allowed us to realize that GPCR functionality is dependent upon many other proteins outside of the heptahelical core, on the site of GPCR expression in a tissue or a microdomain in a cell, and, most importantly, on the formation of differential 'active' states preferentially coupled to specific signal transduction structures. The recognition of such signaling diversity has facilitated the ability to appreciate and identify ligands for GPCRs that demonstrate a bias towards one signaling form of a receptor to another. However while potentially increasing our ability for selective signal targeting, our approach to understanding the physiological ramifications of systemic signaling manipulation is underdeveloped. This explosion in the complexity of GPCR signaling is now becoming familiar territory to receptor biologists, yet the application of this knowledge to drug design is relatively limited. This review will attempt to outline potential pitfalls and unseen benefits of using signaling bias in therapeutic design as well as highlighting new applications such as Game Theory for uncovering new therapeutic applications for biased agonists.
C1 [Maudsley, S.] NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Patel, S. A.] Univ Maryland Baltimore Cty, Cognit Robot & Learning Lab, Dept Comp Sci & Elect Engn, Baltimore, MD 21228 USA.
[Luttrell, L. M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA.
[Martin, B.] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
FU National Institutes of Health [DK55524]; Research Service of the
Charleston Veterans Affairs Medical Centers
FX This work was supported in-part by the Intramural Research Program of
the National Institutes of Health. LML is supported by National
Institutes of Health Grants DK55524 and the Research Service of the
Charleston Veterans Affairs Medical Centers.
NR 77
TC 18
Z9 18
U1 2
U2 12
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-5575
J9 MINI-REV MED CHEM
JI Mini-Rev. Med. Chem.
PD AUG
PY 2012
VL 12
IS 9
BP 831
EP 840
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 975OR
UT WOS:000306521100005
PM 22681251
ER
PT J
AU Nagao, K
Kobayashi, T
Moro, K
Ohyama, M
Adachi, T
Kitashima, DY
Ueha, S
Horiuchi, K
Tanizaki, H
Kabashima, K
Kubo, A
Cho, YH
Clausen, BE
Matsushima, K
Suematsu, M
Furtado, GC
Lira, SA
Farber, JM
Udey, MC
Amagai, M
AF Nagao, Keisuke
Kobayashi, Tetsuro
Moro, Kazuyo
Ohyama, Manabu
Adachi, Takeya
Kitashima, Daniela Y.
Ueha, Satoshi
Horiuchi, Keisuke
Tanizaki, Hideaki
Kabashima, Kenji
Kubo, Akiharu
Cho, Young-hun
Clausen, Bjorn E.
Matsushima, Kouji
Suematsu, Makoto
Furtado, Glaucia C.
Lira, Sergio A.
Farber, Joshua M.
Udey, Mark C.
Amagai, Masayuki
TI Stress-induced production of chemokines by hair follicles regulates the
trafficking of dendritic cells in skin
SO NATURE IMMUNOLOGY
LA English
DT Article
ID EPIDERMAL LANGERHANS CELLS; STEADY-STATE CONDITIONS; LYMPHOID ORGANS;
STEM-CELLS; CONTACT HYPERSENSITIVITY; IMMUNE PRIVILEGE; NULL MICE;
T-CELLS; IN-VIVO; BULGE
AB Langerhans cells (LCs) are epidermal dendritic cells with incompletely understood origins that associate with hair follicles for unknown reasons. Here we show that in response to external stress, mouse hair follicles recruited Gr-1(hi) monocyte-derived precursors of LCs whose epidermal entry was dependent on the chemokine receptors CCR2 and CCR6, whereas the chemokine receptor CCR8 inhibited the recruitment of LCs. Distinct hair-follicle regions had differences in their expression of ligands for CCR2 and CCR6. The isthmus expressed the chemokine CCL2; the infundibulum expressed the chemokine CCL20; and keratinocytes in the bulge produced the chemokine CCL8, which is the ligand for CCR8. Thus, distinct hair-follicle keratinocyte subpopulations promoted or inhibited repopulation with LCs via differences in chemokine production, a feature also noted in humans. Pre-LCs failed to enter hairless skin in mice or humans, which establishes hair follicles as portals for LCs.
C1 [Nagao, Keisuke; Kobayashi, Tetsuro; Ohyama, Manabu; Adachi, Takeya; Kitashima, Daniela Y.; Kubo, Akiharu; Amagai, Masayuki] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan.
[Moro, Kazuyo] RIKEN Res Ctr Allergy & Immunol, Lab Immune Cell Syst, Yokohama, Kanagawa, Japan.
[Ueha, Satoshi; Matsushima, Kouji] Univ Tokyo, Dept Prevent Med, Tokyo, Japan.
[Horiuchi, Keisuke] Keio Univ, Sch Med, Dept Orthoped, Tokyo, Japan.
[Horiuchi, Keisuke; Kubo, Akiharu] Keio Univ, Sch Med, Ctr Integrated Med Res, Tokyo, Japan.
[Tanizaki, Hideaki; Kabashima, Kenji] Kyoto Univ, Fac Med, Dept Dermatol, Kyoto 606, Japan.
[Cho, Young-hun; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Clausen, Bjorn E.] Erasmus Univ, Dept Immunol, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Suematsu, Makoto] Keio Univ, Sch Med, Dept Biochem, Tokyo, Japan.
[Suematsu, Makoto] Japan Sci & Technol Agcy, Exploratory Res Adv Technol, Suematsu Gas Biol Project, Tokyo, Japan.
[Furtado, Glaucia C.; Lira, Sergio A.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA.
[Farber, Joshua M.] NIAID, Lab Mol Immunol, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Nagao, K (reprint author), Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan.
EM nagaok@med.keio.ac.jp
RI CLAUSEN, Bjorn/A-8229-2010; Nagao, Keisuke/J-5116-2013; Amagai,
Masayuki/K-5325-2013; Kabashima, Kenji/G-2521-2014; Ohyama,
Manabu/J-5524-2014; Kubo, Akiharu/I-2711-2014; Horiuchi,
Keisuke/L-2277-2013; Moro, Kazuyo/A-5987-2016; Suematsu,
Makoto/I-8135-2013
OI CLAUSEN, Bjorn/0000-0002-2484-7842; Nagao, Keisuke/0000-0002-7005-3138;
Amagai, Masayuki/0000-0003-3314-7052; Kabashima,
Kenji/0000-0002-0773-0554; Ohyama, Manabu/0000-0002-2662-5717; Kubo,
Akiharu/0000-0003-0902-3586; Horiuchi, Keisuke/0000-0001-7063-9609;
Suematsu, Makoto/0000-0002-7165-6336
FU Japan Society for the Promotion of Science; Kanae Foundation for the
Promotion of Medical Science; Japaneses Dermatological Association;
Netherlands Organization for Scientific Research; Intramural Research
Program of the Center for Cancer Research of the National Cancer
Institute
FX We thank K. Eguchi and H. Ito for assistance, and M. Kajimura for
assistance with multiphoton microscopy. Supported by the Japan Society
for the Promotion of Science (K.N. and M.A.), The Kanae Foundation for
the Promotion of Medical Science, and Japaneses Dermatological
Association (K.N.), The Netherlands Organization for Scientific Research
(B.E.C.) and the Intramural Research Program of the Center for Cancer
Research of the National Cancer Institute (M.C.U.).
NR 48
TC 91
Z9 92
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2012
VL 13
IS 8
BP 744
EP +
DI 10.1038/ni.2353
PG 11
WC Immunology
SC Immunology
GA 976GT
UT WOS:000306569600010
PM 22729248
ER
PT J
AU Torre, P
Zeldow, B
Hoffman, HJ
Buchanan, A
Siberry, GK
Rice, M
Sirois, PA
Williams, PL
AF Torre, Peter, III
Zeldow, Bret
Hoffman, Howard J.
Buchanan, Ashley
Siberry, George K.
Rice, Mabel
Sirois, Patricia A.
Williams, Paige L.
CA Pediat HIV AIDS Cohort Study
TI Hearing Loss in Perinatally HIV-infected and HIV-exposed but Uninfected
Children and Adolescents
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE perinatal HIV exposure; perinatal HIV infection; hearing loss;
antiretroviral therapy
ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; HARD-OF-HEARING; OTITIS-MEDIA;
ANTIRETROVIRAL THERAPY; PREVALENCE; AGE; LANGUAGE; MUTATION; MOTHERS;
DEAF
AB Background: Little is known about hearing loss in children with HIV infection (HIV+). We examined the prevalence of hearing loss in perinatally HIV+ and HIV-exposed but uninfected (HEU) children, compared these with the percentage with hearing loss in the general population and evaluated possible risk factors for hearing loss in HIV+ and HEU children.
Methods: Audiometric examinations were completed in children who met any prespecified criteria for possible hearing loss. The hearing examination consisted of a tympanogram in each ear and pure-tone air-conduction threshold testing from 500 through 4000 Hz. Hearing loss was defined as the pure-tone average over these frequencies >= 20 dB hearing level. The associations of demographic variables, parent/caregiver, HIV disease and HIV treatment with hearing loss were evaluated with univariate and multi-variable logistic regression models.
Results: Hearing testing was completed in 231 children (145 HIV+ and 86 HEU). Hearing loss occurred in 20.0% of HIV+ children and 10.5% of HEU children. After adjusting for caregiver education level, HIV infection was associated with increased odds of hearing loss (adjusted odds ratio = 2.13, 95% confidence interval: 0.95-4.76, P = 0.07). Among HIV+ children, those with a Centers for Disease Control and Prevention class C diagnosis had over twice the odds of hearing loss (adjusted odds ratio = 2.47, 95% confidence interval: 1.04-5.87, P = 0.04). The prevalence of hearing loss was higher in both HIV+ and HEU children compared with National Health and Nutrition Examination Survey III children.
Conclusions: Hearing loss was more common in both HIV+ and HEU children than in children from a US population sample. More advanced HIV illness increased the risk of hearing loss in HIV+ children.
C1 [Torre, Peter, III] San Diego State Univ, Sch Speech Language & Hearing Sci, San Diego, CA 92182 USA.
[Zeldow, Bret; Buchanan, Ashley; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, Bethesda, MD USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Rice, Mabel] Univ Kansas, Dept Speech Language Hearing Sci & Disorders, Lawrence, KS 66045 USA.
[Sirois, Patricia A.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
RP Torre, P (reprint author), San Diego State Univ, Sch Speech Language & Hearing Sci, 5500 Campanile Dr,SLHS 244, San Diego, CA 92182 USA.
EM ptorre@mail.sdsu.edu
RI Sanders, Matthew/C-1941-2013;
OI Sanders, Matthew/0000-0003-3479-6337; Rice, Mabel/0000-0002-8150-5523
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute on Drug Abuse; National Institute of
Allergy and Infectious Diseases; National Institute of Mental Health;
National Institute of Neurological Disorders and Stroke; National
Institute on Deafness and Other Communication Disorders; National Heart
Lung and Blood Institute; National Institute on Alcohol Abuse and
Alcoholism; Harvard University School of Public Health [HD052102];
Tulane University School of Medicine [HD052104]
FX The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development with
co-funding from the National Institute on Drug Abuse, the National
Institute of Allergy and Infectious Diseases, the National Institute of
Mental Health, the National Institute of Neurological Disorders and
Stroke, the National Institute on Deafness and Other Communication
Disorders, the National Heart Lung and Blood Institute and the National
Institute on Alcohol Abuse and Alcoholism through cooperative agreements
with the Harvard University School of Public Health (HD052102)
(Principal Investigator: George Seage; Project Director: Julie Alperen)
and the Tulane University School of Medicine (HD052104) (Principal
Investigator: Russell Van Dyke; Co-Principal Investigator: Kenneth Rich;
Project Director: Patrick Davis). Data management services were provided
by Frontier Science and Technology Research Foundation (PI: Suzanne
Siminski), and regulatory services and logistical support were provided
by Westat, Inc (PI: Julie Davidson). The conclusions and opinions
expressed in this article are those of the authors and do not
necessarily reflect those of the National Institutes of Health or U. S.
Department of Health and Human Services. The authors have no other
conflicts of interest or funding to disclose.
NR 30
TC 14
Z9 14
U1 1
U2 4
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 AUG
PY 2012
VL 31
IS 8
BP 835
EP 841
DI 10.1097/INF.0b013e31825b9524
PG 7
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 976HR
UT WOS:000306572500015
PM 22549437
ER
PT J
AU Schmidt, DS
Bieging, KT
Gomez-de-Leon, P
Villasenor-Sierra, A
Inostroza, J
Robbins, JB
Schneerson, R
Carlone, GM
Romero-Steiner, S
AF Schmidt, Daniel S.
Bieging, Kathryn T.
Gomez-de-Leon, Patricia
Villasenor-Sierra, Alberto
Inostroza, Jaime
Robbins, John B.
Schneerson, Rachel
Carlone, George M.
Romero-Steiner, Sandra
TI MEASUREMENT OF HAEMOPHILUS INFLUENZAE TYPE A CAPSULAR POLYSACCHARIDE
ANTIBODIES IN CORD BLOOD SERA
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE Haemophilus influenzae type a; enzyme-linked immunosorbent assay;
anticapsular antibodies
ID CONJUGATE VACCINE; DISEASE; EPIDEMIOLOGY; CHILDREN; UTAH
AB We measured anti-Haemophilus influenzae type a capsular polysaccharide serum immunoglobulin G antibodies in cord blood sera from Mexican (n = 68) and Chilean mothers (n = 72) by enzyme-linked immunosorbent assay. Measurable antibodies were found in 79.3% of samples. Immunoglobulin G antibodies correlated with serum bactericidal activity (r = 0.66). This enzyme-linked immunosorbent assay can be used for the evaluation of adaptive immune responses to Haemophilus influenzae type a and serosurveillance studies in populations at risk.
C1 [Romero-Steiner, Sandra] Ctr Dis Control & Prevent, Div Bacterial Dis, Immunol Labs, MVPDB DBD NCIRD CCID, Atlanta, GA 30333 USA.
[Gomez-de-Leon, Patricia] Univ Nacl Autonoma Mexico, Dept Salud Publ, Fac Med, Mexico City 04510, DF, Mexico.
[Villasenor-Sierra, Alberto] IMSS, CIBO, Guadalajara, Jal, Mexico.
[Inostroza, Jaime] Univ La Frontera, Fac Med, Dept Basic Sci, Dr Hernan A Henriquez Hosp,Immunol Lab, Temuco, Chile.
[Robbins, John B.; Schneerson, Rachel] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Romero-Steiner, S (reprint author), Ctr Dis Control & Prevent, Div Bacterial Dis, Immunol Labs, MVPDB DBD NCIRD CCID, Bldg 18,Room B-105,MS A-36,1600 Clifton Rd, Atlanta, GA 30333 USA.
EM Ssteiner@cdc.gov
OI Romero-Steiner, Sandra/0000-0003-4128-7768
FU Intramural NIH HHS [Z99 HD999999]
NR 11
TC 3
Z9 4
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 AUG
PY 2012
VL 31
IS 8
BP 876
EP 878
DI 10.1097/INF.0b013e31825ab166
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 976HR
UT WOS:000306572500026
PM 22549435
ER
PT J
AU Marczak, ED
Marzec, J
Zeldin, DC
Kleeberger, SR
Brown, NJ
Pretorius, M
Lee, CR
AF Marczak, Ewa D.
Marzec, Jacqui
Zeldin, Darryl C.
Kleeberger, Steven R.
Brown, Nancy J.
Pretorius, Mias
Lee, Craig R.
TI Polymorphisms in the transcription factor NRF2 and forearm vasodilator
responses in humans
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE bradykinin; NFE2L2; NRF2; polymorphism; sodium nitroprusside; vascular
function
ID ENDOTHELIAL-CELLS; OXIDATIVE STRESS; VASCULAR-DISEASE; GENE-EXPRESSION;
NITRIC-OXIDE; IN-VIVO; DYSFUNCTION; PATHWAY; RISK; ASSOCIATION
AB Objective Oxidative stress is integral to the development of endothelial dysfunction and cardiovascular disease. As NRF2 is a key transcription factor in antioxidant defense, we aimed to determine whether polymorphisms within the promoter region of the gene encoding NRF2 (NFE2L2) would significantly modify vasodilator responses in humans.
Methods Associations between the - 653A/G (rs35652124), - 651G/A (rs6706649), and - 617C/A (rs6721961) polymorphisms within the NFE2L2 promoter and vascular function were evaluated in healthy African-American (n=64) and white (n=184) individuals. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography at baseline and in response to incremental doses of bradykinin or sodium nitroprusside. Forearm vascular resistance (FVR) was calculated as the mean arterial pressure/FBF.
Results In African Americans, - 653G variant allele carriers had significantly lower FBF and higher FVR under basal conditions as well as in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). In whites, although no significant associations were observed with the -653A/G genotype, - 617A variant allele carriers had significantly higher FVR at baseline and in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P < 0.05 for each comparison). The -651G/A polymorphism was not associated with vasodilator responses in either racial group.
Conclusion Polymorphisms within the NFE2L2 promoter were associated with impaired forearm vasodilator responses in an endothelial-independent manner, suggesting an important role of NRF2 in the regulation of vascular function in humans. Pharmacogenetics and Genomics 22: 620-628 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Lee, Craig R.] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Marczak, Ewa D.; Marzec, Jacqui; Zeldin, Darryl C.; Kleeberger, Steven R.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Brown, Nancy J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN USA.
[Brown, Nancy J.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Nashville, TN 37232 USA.
[Pretorius, Mias] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA.
RP Lee, CR (reprint author), Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, CB 7569,Kerr Hall, Chapel Hill, NC 27599 USA.
EM craig_lee@unc.edu
OI Lee, Craig/0000-0003-3595-5301
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES025034, Z01 ES100513, DK38226,
HL65195, HL060906, HL085740]; American Heart Association
FX This study was supported by funds from the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences to Dr
Zeldin (Z01 ES025034) and Dr Kleeberger (Z01 ES100513), grants DK38226,
HL65195, and HL060906 to Dr Brown, grant HL085740 to Dr Pretorius, and a
Beginning Grant-in-Aid from the American Heart Association to Dr Lee.
Its contents are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH.
NR 27
TC 18
Z9 20
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1744-6872
J9 PHARMACOGENET GENOM
JI Pharmacogenet. Genomics
PD AUG
PY 2012
VL 22
IS 8
BP 620
EP 628
DI 10.1097/FPC.0b013e32835516e5
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA 975CD
UT WOS:000306483500006
PM 22668754
ER
PT J
AU Park, Y
Lee-Kim, J
Killen, M
Park, K
Kim, J
AF Park, Yoonjung
Lee-Kim, Jennie
Killen, Melanie
Park, Kyoungja
Kim, Jihyun
TI Korean Children's Evaluation of Parental Restrictions Regarding
Gender-stereotypic Peer Activities
SO SOCIAL DEVELOPMENT
LA English
DT Article
DE gender stereotypes; peer relationships; fairness; culture
ID SCHOOL CONTEXTS; AUTHORITY; ADOLESCENTS; EXCLUSION; CONCEPTIONS; FAMILY;
PERCEPTIONS; INCLUSION; CHILDHOOD; JUDGMENTS
AB Korean children's evaluations of parental restrictions of children's activities based on gender stereotypic expectations were investigated. Third and sixth grade Korean (N = 128) children evaluated scenarios in which a boy or girl desired to play ballet or soccer. Participants used stereotypes to support children's desires to play gender-consistent activities and adhered to parental authority for choice of gender-consistent social activities. Yet, they also rejected parental decisions to treat sons and daughters differently based on the view that it would be unfair. Stereotypic expectations decreased with age and were used more by boys than by girls when evaluating exclusion. The results are discussed in terms of exclusion, development, and culture.
C1 [Park, Yoonjung] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Lee-Kim, Jennie; Killen, Melanie] Univ Maryland, College Pk, MD 20742 USA.
[Park, Kyoungja] Yonsei Univ, Seoul 120749, South Korea.
[Kim, Jihyun] Hanyang Cyber Univ, Ansan, South Korea.
RP Park, Y (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM parkyoon@mail.nih.gov
NR 52
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-205X
J9 SOC DEV
JI Soc. Dev.
PD AUG
PY 2012
VL 21
IS 3
BP 577
EP 591
DI 10.1111/j.1467-9507.2011.00643.x
PG 15
WC Psychology, Developmental
SC Psychology
GA 975KS
UT WOS:000306510800009
ER
PT J
AU Forman, J
Taruscio, D
Llera, VA
Barrera, LA
Cote, TR
Edfjall, C
Gavhed, D
Haffner, ME
Nishimura, Y
Posada, M
Tambuyzer, E
Groft, SC
Henter, JI
AF Forman, John
Taruscio, Domenica
Llera, Virginia A.
Barrera, Luis A.
Cote, Timothy R.
Edfjaell, Catarina
Gavhed, Desiree
Haffner, Marlene E.
Nishimura, Yukiko
Posada, Manuel
Tambuyzer, Erik
Groft, Stephen C.
Henter, Jan-Inge
CA Int Conference Rare Dis Orphan
TI The need for worldwide policy and action plans for rare diseases
SO ACTA PAEDIATRICA
LA English
DT Article
DE Rare diseases; Orphan drugs; Public health
ID LESSONS
AB There are more than 6000 rare diseases (defined as affecting <5/10 000 individuals in Europe, <200 000 people in the United States). The rarity can create problems including: difficulties in obtaining timely, accurate diagnoses; lack of experienced healthcare providers; useful, reliable and timely information may be hard to find; research activities are less common; developing new medicines may not be economically feasible; treatments are sometimes very expensive; and in developing countries, the problems are compounded by other resource limitations. Emphasis is required to support appropriate research and development leading to better prevention, diagnosis and treatments of rare diseases. Notably, clinical trials using already existing drugs may result in new, affordable, treatment strategies. Moreover, rare diseases may teach us about common disorders. Conclusions: Countries are encouraged to implement specific research and development activities within their individual capabilities, so that patients worldwide have equal access to necessary interventions to maximize the potential of every individual.
C1 [Forman, John] New Zealand Org Rare Disorders, Wellington Mail Ctr, Wellington 5045, New Zealand.
[Taruscio, Domenica] Ist Super Sanita, Natl Ctr Rare Dis, I-00161 Rome, Italy.
[Llera, Virginia A.] Fdn GEISER, Mendoza, Argentina.
[Barrera, Luis A.] Javeriana Univ, Inst Inborn Errors Metab, Bogota, Colombia.
[Cote, Timothy R.] Natl Org Rare Disorders, Washington, DC USA.
[Edfjaell, Catarina] Shire AG, Shire Human Genet Therapies, Eysins, Switzerland.
[Gavhed, Desiree; Henter, Jan-Inge] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.
[Haffner, Marlene E.] Haffner Associates, Rockville, MD USA.
[Nishimura, Yukiko] Univ Tokyo, Tokyo, Japan.
[Posada, Manuel] Inst Salud Carlos III, Res Inst Rare Dis, Madrid, Spain.
[Tambuyzer, Erik] ABConsult, Louvain, Belgium.
[Groft, Stephen C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA.
RP Forman, J (reprint author), New Zealand Org Rare Disorders, Wellington Mail Ctr, POB 38-538, Wellington 5045, New Zealand.
EM exec.director@nzord.org.nz; jan-inge.henter@ki.se
RI TARUSCIO, DOMENICA/A-6646-2015;
OI TARUSCIO, DOMENICA/0000-0001-5403-233X; Gavhed,
Desiree/0000-0003-3849-9268; Posada, Manuel/0000-0002-8372-4180
NR 7
TC 21
Z9 21
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0803-5253
J9 ACTA PAEDIATR
JI Acta Paediatr.
PD AUG
PY 2012
VL 101
IS 8
BP 805
EP 807
DI 10.1111/j.1651-2227.2012.02705.x
PG 3
WC Pediatrics
SC Pediatrics
GA 973ZA
UT WOS:000306398200021
PM 22519914
ER
PT J
AU Gwon, AR
Park, JS
Arumugam, TV
Kwon, YK
Chan, SL
Kim, SH
Baik, SH
Yang, S
Yun, YK
Choi, Y
Kim, S
Tang, SC
Hyun, DH
Cheng, AW
Dann, CE
Bernier, M
Lee, J
Markesbery, WR
Mattson, MP
Jo, DG
AF Gwon, A-Ryeong
Park, Jong-Sung
Arumugam, Thiruma V.
Kwon, Yong-Kook
Chan, Sic L.
Kim, Seol-Hee
Baik, Sang-Ha
Yang, Sunghee
Yun, Young-Kwang
Choi, Yuri
Kim, Saerom
Tang, Sung-Chun
Hyun, Dong-Hoon
Cheng, Aiwu
Dann, Charles E., III
Bernier, Michel
Lee, Jaewon
Markesbery, William R.
Mattson, Mark P.
Jo, Dong-Gyu
TI Oxidative lipid modification of nicastrin enhances amyloidogenic
?-secretase activity in Alzheimer's disease
SO AGING CELL
LA English
DT Article
DE Alzheimer's disease; amyloid; lipid peroxidation; nicastrin; oxidative
stress; -secretase
ID MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE; A-BETA; ISCHEMIC-STROKE;
NEURONAL DEATH; MOUSE MODEL; STRESS; PEROXIDATION; BRAIN; METABOLISM
AB The cause of elevated level of amyloid beta-peptide (A beta 42) in common late-onset sporadic [Alzheimers disease (AD)] has not been established. Here, we show that the membrane lipid peroxidation product 4-hydroxynonenal (HNE) is associated with amyloid and neurodegenerative pathologies in AD and that it enhances ?-secretase activity and A beta 42 production in neurons. The ?-secretase substrate receptor, nicastrin, was found to be modified by HNE in cultured neurons and in brain specimens from patients with AD, in which HNEnicastrin levels were found to be correlated with increased ?-secretase activity and A beta plaque burden. Furthermore, HNE modification of nicastrin enhanced its binding to the ?-secretase substrate, amyloid precursor protein (APP) C99. In addition, the stimulation of ?-secretase activity and A beta 42 production by HNE were blocked by an HNE-scavenging histidine analog in a 3xTgAD mouse model of AD. These findings suggest a specific molecular mechanism by which oxidative stress increases A beta 42 production in AD and identify HNE as a novel therapeutic target upstream of the ?-secretase cleavage of APP.
C1 [Arumugam, Thiruma V.; Chan, Sic L.; Tang, Sung-Chun; Hyun, Dong-Hoon; Cheng, Aiwu; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia.
[Kwon, Yong-Kook] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
[Chan, Sic L.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA.
[Tang, Sung-Chun] Natl Taiwan Univ Hosp, Dept Neurol, Yun Lin Branch, Taipei, Taiwan.
[Hyun, Dong-Hoon] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul, South Korea.
[Dann, Charles E., III] Indiana Univ, Dept Chem, Bloomington, IN USA.
[Bernier, Michel] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Lee, Jaewon] Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea.
[Markesbery, William R.] Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Gwon, A-Ryeong; Park, Jong-Sung; Kim, Seol-Hee; Baik, Sang-Ha; Yang, Sunghee; Yun, Young-Kwang; Choi, Yuri; Kim, Saerom; Jo, Dong-Gyu] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Arumugam, Thiruma/B-4898-2011; Lee, Jaewon/N-9064-2013
FU Intramural Research Program of the National Institute on Aging; National
Research Foundation of Korea (NRF); Ministry of Education, Science and
Technology [2010-0000593]; Korea Healthcare technology R&D Project,
Ministry for Health, Welfare & Family Affairs, Republic of Korea
[A092042]
FX We thank G. Yu for his valuable comments during the preparation of the
manuscript. This research was supported by the Intramural Research
Program of the National Institute on Aging, and by the National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology (2010-0000593), and Korea Healthcare technology R&D
Project, Ministry for Health, Welfare & Family Affairs, Republic of
Korea (A092042).
NR 46
TC 21
Z9 21
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2012
VL 11
IS 4
BP 559
EP 568
DI 10.1111/j.1474-9726.2012.00817.x
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 973ZY
UT WOS:000306400600001
PM 22404891
ER
PT J
AU Wilkinson, JE
Burmeister, L
Brooks, SV
Chan, CC
Friedline, S
Harrison, DE
Hejtmancik, JF
Nadon, N
Strong, R
Wood, LK
Woodward, MA
Miller, RA
AF Wilkinson, John E.
Burmeister, Lisa
Brooks, Susan V.
Chan, Chi-Chao
Friedline, Sabrina
Harrison, David E.
Hejtmancik, James F.
Nadon, Nancy
Strong, Randy
Wood, Lauren K.
Woodward, Maria A.
Miller, Richard A.
TI Rapamycin slows aging in mice
SO AGING CELL
LA English
DT Article
DE interventions; longevity pathology; TOR
ID AMES DWARF MICE; GENETICALLY HETEROGENEOUS MICE; LIFE-SPAN EXTENSION;
SIGNALING PATHWAY; CELL-CYCLE; TOR; TARGET; CANCER; AGE; RESTRICTION
AB Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action.
C1 [Wilkinson, John E.; Burmeister, Lisa; Friedline, Sabrina; Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Burmeister, Lisa; Friedline, Sabrina; Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Wilkinson, John E.] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
[Brooks, Susan V.; Wood, Lauren K.] Univ Michigan, Dept Mol & Integrat Physiol & Biomed Engn, Ann Arbor, MI 48109 USA.
[Chan, Chi-Chao] NEI, Histol Core, NIH, Bethesda, MD 20892 USA.
[Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Hejtmancik, James F.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Nadon, Nancy] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
[Woodward, Maria A.] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA.
[Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
RP Miller, RA (reprint author), Univ Michigan, Dept Pathol, BSRB Room 3001,Box 2200,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM millerr@umich.edu
OI Zaseck, Lauren/0000-0002-8604-0032
FU [AG022303]; [AG007996]; [AG013283]
FX This work was supported by grants AG022303, AG007996, and AG013283. We
thank Vivian Diaz, Lynn Winkleman, and Mike Astle for expert technical
assistance.
NR 35
TC 208
Z9 213
U1 2
U2 39
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2012
VL 11
IS 4
BP 675
EP 682
DI 10.1111/j.1474-9726.2012.00832.x
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 973ZY
UT WOS:000306400600014
PM 22587563
ER
PT J
AU Fao, P
Fao, P
Ky-Zerbo, O
Gouem, C
Somda, P
Hien, H
Ouedraogo, PE
Kania, D
Sanou, A
Kossiwavi, IA
Sanogo, B
Ouedraogo, M
Siribie, I
Valea, D
Ouedraogo, S
Some, R
Rouet, F
Rollins, N
McFetridge, L
Naidu, K
Luchters, S
Reyners, M
Irungu, E
Katingima, C
Mwaura, M
Ouattara, G
Mandaliya, K
Wambua, S
Thiongo, M
Nduati, R
Kose, J
Njagi, E
Mwaura, P
Newell, ML
Mepham, S
Viljoen, J
Bland, R
Mthethwa, L
Bazin, B
Rekacewicz, C
Taylor, A
Flowers, N
Thigpen, M
Fowler, MG
Jamieson, D
Mofenson, LM
Read, JS
Bork, K
Cames, C
Cournil, A
Claeys, P
Temmerman, M
Luchters, S
Van de Perre, P
Becquart, P
Foulongne, V
Segondy, M
de Vincenzi, I
Gaillard, P
Farley, T
Habib, N
Landoulsi, S
AF Fao, Paulin
Fao, Paulin
Ky-Zerbo, Odette
Gouem, Clarisse
Somda, Paulin
Hien, Herve
Ouedraogo, Patrice Elysee
Kania, Dramane
Sanou, Armande
Kossiwavi, Ida Ayassou
Sanogo, Bintou
Ouedraogo, Moussa
Siribie, Issa
Valea, Diane
Ouedraogo, Sayouba
Some, Roseline
Rouet, Francois
Rollins, Nigel
McFetridge, Lynne
Naidu, Kevi
Luchters, Stanley
Reyners, Marcel
Irungu, Eunice
Katingima, Christine
Mwaura, Mary
Ouattara, Gina
Mandaliya, Kishor
Wambua, Sammy
Thiongo, Mary
Nduati, Ruth
Kose, Judith
Njagi, Ephantus
Mwaura, Peter
Newell, Marie-Louise
Mepham, Stephen
Viljoen, Johannes
Bland, Ruth
Mthethwa, Londiwe
Bazin, Brigitte
Rekacewicz, Claire
Taylor, Allan
Flowers, Nicole
Thigpen, Michael
Fowler, Mary Glenn
Jamieson, Denise
Mofenson, Lynne M.
Read, Jennifer S.
Bork, Kirsten
Cames, Cecile
Cournil, Amandine
Claeys, Patricia
Temmerman, Marleen
Luchters, Stanley
Van de Perre, Philippe
Becquart, Pierre
Foulongne, Vincent
Segondy, Michel
de Vincenzi, Isabelle
Gaillard, Philippe
Farley, Tim
Habib, Ndema
Landoulsi, Sihem
CA Kesho Bora Study Grp
TI Maternal HIV-1 Disease Progression 18-24 Months Postdelivery According
to Antiretroviral Prophylaxis Regimen (Triple-Antiretroviral Prophylaxis
During Pregnancy and Breastfeeding vs Zidovudine/Single-Dose Nevirapine
Prophylaxis): The Kesho Bora Randomized Controlled Trial
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID INFECTED ADULTS; TRANSMISSION; INTERRUPTION; THERAPY; WOMEN
AB Background. Antiretroviral (ARV) prophylaxis effectively reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV). However, it is unclear whether stopping ARVs after breastfeeding cessation affects maternal HIV disease progression. We assessed 18-24-month postpartum disease progression risk among women in a randomized trial assessing efficacy and safety of prophylactic maternal ARVs.
Methods. From 2005 to 2008, HIV-infected pregnant women with CD4(+) counts of 200-500/mm(3) were randomized to receive either triple ARV (zidovudine, lamivudine, and lopinavir/ritonavir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose nevirapine without postpartum prophylaxis). Maternal disease progression was defined as the combined endpoint of death, World Health Organization clinical stage 4 disease, or CD4(+) counts of <200/mm(3).
Results. Among 824 randomized women, 789 had at least 1 study visit after cessation of ARV prophylaxis. Following delivery, progression risk up to 24 months postpartum in the triple ARV arm was significantly lower than in the AZT/sdNVP arm (15.7% vs 28.3%; P = .001), but the risks of progression after cessation of ARV prophylaxis (rather than after delivery) were not different (15.0% vs 13.8% 18 months after ARV cessation). Among women with CD4(+) counts of 200-349/mm(3) at enrollment, 24.0% (95% confidence interval [CI], 15.7-35.5) progressed with triple ARV, and 23.0% (95% CI, 17.8-29.5) progressed with AZT/sdNVP, whereas few women in either arm (<5%) with initial CD4(+) counts of >= 350/mm(3) progressed.
Conclusions. Interrupting prolonged triple ARV prophylaxis had no effect on HIV progression following cessation (compared with AZT/sdNVP). However, women on triple ARV prophylaxis had lower progression risk during the time on triple ARV. Given the high rate of progression among women with CD4(+) cells of <350/mm(3), ARVs should not be discontinued in this group.
C1 [Fao, Paulin; Fao, Paulin; Ky-Zerbo, Odette; Gouem, Clarisse; Somda, Paulin; Hien, Herve; Ouedraogo, Patrice Elysee; Kania, Dramane; Sanou, Armande; Kossiwavi, Ida Ayassou; Sanogo, Bintou; Ouedraogo, Moussa; Siribie, Issa; Valea, Diane; Ouedraogo, Sayouba; Some, Roseline; Rouet, Francois; Kesho Bora Study Grp] Ctr Muraz, Bobo Dioulasso, Burkina Faso.
[Rollins, Nigel; McFetridge, Lynne; Naidu, Kevi] Univ KwaZulu Natal, Durban, South Africa.
[Luchters, Stanley; Reyners, Marcel; Irungu, Eunice; Katingima, Christine; Mwaura, Mary; Ouattara, Gina; Mandaliya, Kishor; Wambua, Sammy; Thiongo, Mary] Int Ctr Reprod Hlth, Mombasa, Kenya.
[Nduati, Ruth; Kose, Judith; Njagi, Ephantus; Mwaura, Peter] Network AIDS Researchers E & So Africa, Nairobi, Kenya.
[Newell, Marie-Louise; Mepham, Stephen; Viljoen, Johannes; Bland, Ruth; Mthethwa, Londiwe] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Somkhele, South Africa.
[Taylor, Allan; Flowers, Nicole; Thigpen, Michael; Fowler, Mary Glenn; Jamieson, Denise] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Mofenson, Lynne M.; Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Bork, Kirsten; Cames, Cecile; Cournil, Amandine] IRD, Montpellier, France.
[Claeys, Patricia; Temmerman, Marleen; Luchters, Stanley] Univ Ghent, ICRH, B-9000 Ghent, Belgium.
[Van de Perre, Philippe; Becquart, Pierre; Foulongne, Vincent; Segondy, Michel] Univ Montpellier I, EA Transmiss Pathogenese & Prevent Infect VIH 420, CHU Montpellier, Lab Bacteriol Virol, Montpellier, France.
[de Vincenzi, Isabelle; Gaillard, Philippe; Farley, Tim; Habib, Ndema; Landoulsi, Sihem] WHO, CH-1211 Geneva, Switzerland.
RP Fao, P (reprint author), Ctr Muraz, Bobo Dioulasso, Burkina Faso.
RI Van de Perre, Philippe/B-9692-2008
OI Van de Perre, Philippe/0000-0002-3912-0427
FU Agence Nationale de Recherche sur le Sida et les hepatites virales;
Department for International Development; European and Developing
Countries Clinical Trials Partnership; Thrasher Research Fund; Belgian
Directorate General for International Cooperation; US Centers for
Disease Control and Prevention; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; UNDP/UNFPA/World
Bank/WHO Special Programme of Research, Development and Research
Training in Human Reproduction
FX Financial support was provided by Agence Nationale de Recherche sur le
Sida et les hepatites virales; Department for International Development;
European and Developing Countries Clinical Trials Partnership; Thrasher
Research Fund; Belgian Directorate General for International
Cooperation; US Centers for Disease Control and Prevention; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; and UNDP/UNFPA/World Bank/WHO Special Programme of
Research, Development and Research Training in Human Reproduction.
NR 19
TC 14
Z9 14
U1 0
U2 11
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 AUG 1
PY 2012
VL 55
IS 3
BP 449
EP 460
DI 10.1093/cid/cis461
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 973MN
UT WOS:000306364300023
ER
PT J
AU Mulligan, K
Harris, DR
Emmanuel, P
Fielding, RA
Worrell, C
Kapogiannis, BG
Monte, D
Sleasman, J
Wilson, CM
Aldrovandi, GM
AF Mulligan, Kathleen
Harris, D. Robert
Emmanuel, Patricia
Fielding, Roger A.
Worrell, Carol
Kapogiannis, Bill G.
Monte, Dina
Sleasman, John
Wilson, Craig M.
Aldrovandi, Grace M.
CA ATN 021 Protocol Team
TI Low Bone Mass in Behaviorally HIV-Infected Young Men on Antiretroviral
Therapy: Adolescent Trials Network Study 021B
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID MINERAL DENSITY; ABACAVIR-LAMIVUDINE; OFFICIAL POSITIONS; HIGH
PREVALENCE; NAIVE PATIENTS; TENOFOVIR DF; CHILDREN; FRACTURE;
EMTRICITABINE; COMBINATION
AB Background. Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV-infected young men and seronegative controls.
Methods. HIV-positive men (N = 199) and HIV-negative controls (N = 53), ages 14-25 years, were studied at 15 Adolescent Trials Network for HIV/AIDS Interventions sites. HIV-positive participants were recruited on the basis of ART status: ART-naive (N = 105) or on a regimen containing a nonnucleoside reverse transcriptase inhibitor (NNRTI; N = 52) or protease inhibitor (PI; N = 42). Bone mineral density (BMD) and content (BMC) and body composition were measured by dual-energy X-ray absorptiometry (DXA).
Results were compared across groups by linear modeling. Bone results were adjusted for race, body mass index (BMI), and type of DXA (Hologic/Lunar). Results. The HIV-positive and HIV-negative groups had comparable median age (21 years) and racial/ethnic distribution. Median times since HIV diagnosis were 1.3, 1.9, and 2.2 years in the ART-naive, NNRTI, and PI groups, respectively (P = .01). Total and regional fat were significantly lower in the ART-naive group compared with seronegative controls. Mean BMD and Z scores were generally lower among HIV-positive participants on ART, particularly in the PI group. Average Z scores for the spine were below zero in all 4 groups, including controls.
Conclusions. Young men on ART with a relatively recent diagnosis of HIV infection have lower bone mass than controls. Longitudinal studies are required to determine the impact of impaired accrual or actual loss of bone during adolescence on subsequent fracture risk.
C1 [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, Div Endocrinol, San Francisco, CA 94110 USA.
[Harris, D. Robert; Monte, Dina] Westat Corp, Rockville, MD USA.
[Emmanuel, Patricia] Univ S Florida, Tampa, FL USA.
[Fielding, Roger A.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Worrell, Carol; Kapogiannis, Bill G.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
[Sleasman, John] Univ S Florida, St Petersburg, FL USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Aldrovandi, Grace M.] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA 90089 USA.
RP Mulligan, K (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Endocrinol, Bldg 30,Room 3501K,1001 Potrero Ave, San Francisco, CA 94110 USA.
EM kathleen.mulligan@ucsf.edu
FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from
the National Institutes of Health through the Eunice Kennedy Shriver
National Institute of Child Health and Human Development [NIH U01 HD
040533, U01 HD 040474]; Department of Health and Human ServicesGeneral
Clinical Research Center (GCRC) Program of the National Center for
Research Resources, NIH, Department of Health and Human Services;
Louisiana Board of Regents RC/EEP [RC/EEP-06]
FX This work was supported by The Adolescent Medicine Trials Network for
HIV/AIDS Interventions (ATN) from the National Institutes of Health [NIH
U01 HD 040533 and U01 HD 040474] through the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (B. G. K., R.
Hazra, C. W.), with supplemental funding from the National Institutes on
Drug Abuse (N. B.) and Mental Health (P. Brouwers, S. Allison).
Additional support for this study was provided at 4 of the participating
sites by grants from the General Clinical Research Center (GCRC) Program
of the National Center for Research Resources, NIH, Department of Health
and Human Services as follows: Children's National Medical Center
(M01RR020359), University of Maryland School of Medicine (M01 RR165001),
University of Pennsylvania/Children's Hospital of Philadelphia
(NCRRUL1-RR-024134), and University of California at San Francisco (UL1
RR024131). The Tulane University Health Sciences Center utilized its
Clinical and Translational Research Center (CTRC) for the study; the
center was supported in whole or in part by funds provided through the
Louisiana Board of Regents RC/EEP (RC/EEP-06).
NR 40
TC 19
Z9 19
U1 0
U2 1
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 AUG 1
PY 2012
VL 55
IS 3
BP 461
EP 468
DI 10.1093/cid/cis455
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 973MN
UT WOS:000306364300024
PM 22573848
ER
PT J
AU Gourgari, E
Saloustros, E
Stratakis, CA
AF Gourgari, Evgenia
Saloustros, Emmanouil
Stratakis, Constantine A.
TI Large-cell calcifying Sertoli cell tumors of the testes in pediatrics
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE Carney complex; gynecomastia; Peutz-Jeghers syndrome; Sertoli tumor;
testicular tumor
ID PEUTZ-JEGHERS-SYNDROME; CORD-STROMAL TUMORS; CARNEY COMPLEX; PREPUBERTAL
GYNECOMASTIA; ENDOCRINE OVERACTIVITY; AROMATASE INHIBITOR; GENE;
FEATURES; BOY; RECOMMENDATIONS
AB Purpose of review
The aim of this review is to describe the clinical, biochemical, radiographic, histological, and functional characteristics of large-cell calcifying Sertoli cell tumors of the testes (LCCSCTs). We describe the two main syndromes associated with these tumors: Peutz-Jeghers syndrome (PJS) caused mainly by mutations in the STK11 (aka LKB1) gene, which encodes a serine-threonine kinase, and Carney complex (CNC), which is most often caused by PRKAR1A mutations, the gene encoding regulatory subunit type 1 of protein kinase A.
Recent findings
Relatively few patients have been reported in the literature with LCCSCTs. In children they often present as prepubertal and/or peripubertal gynecomastia. Although these tumors are very rare, they occur with higher frequency among patients with PJS and CNC. Orchiectomy was often performed in the past; however, these tumors are overwhelmingly benign and, unless there are significant hormonal changes or pain and/or mass effects, there is no need for surgery. Tumors that lead to hyperestrogenemia may be treated efficiently with aromatase inhibitors; any change in appearance should prompt evaluation for malignancy.
Summary
The detection of LCCSCTs may point to an underlying genetic multiple neoplasia syndrome such as PJS or CNC. Surgery is rarely indicated and aromatase inhibitors constitute an effective treatment for those cases that are associated with gynecomastia and/or advanced skeletal age.
C1 [Gourgari, Evgenia; Saloustros, Emmanouil; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Stratakis, CA (reprint author), 31 Ctr Dr,Room 2A46,MSC 2425, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
OI Saloustros, Emmanouil /0000-0002-0485-0120
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD)
FX This study was supported by the Intramural Program of the Eunice Kennedy
Shriver National Institute of Child Health & Human Development (NICHD).
NR 41
TC 9
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8703
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD AUG
PY 2012
VL 24
IS 4
BP 518
EP 522
DI 10.1097/MOP.0b013e328355a279
PG 5
WC Pediatrics
SC Pediatrics
GA 973PM
UT WOS:000306372200014
PM 22732638
ER
PT J
AU Huppke, P
Brendel, C
Korenke, GC
Marquardt, I
Donsante, A
Yi, L
Hicks, JD
Steinbach, PJ
Wilson, C
Elpeleg, O
Moller, LB
Christodoulou, J
Kaler, SG
Gartner, J
AF Huppke, Peter
Brendel, Cornelia
Korenke, Georg Christoph
Marquardt, Iris
Donsante, Anthony
Yi, Ling
Hicks, Julia D.
Steinbach, Peter J.
Wilson, Callum
Elpeleg, Orly
Moller, Lisbeth Birk
Christodoulou, John
Kaler, Stephen G.
Gaertner, Jutta
TI Molecular and Biochemical Characterization of a Unique Mutation in CCS,
the Human Copper Chaperone to Superoxide Dismutase
SO HUMAN MUTATION
LA English
DT Article
DE CCS; SOD1; copper; chaperone
ID MENKES DISEASE; DEFICIENT MICE; MESSENGER-RNA; MOTOR-NEURONS; PROTEIN;
XIAP; METABOLISM; DISORDER; LACKING; WILSON
AB Copper (Cu) is a trace metal that readily gains and donates electrons, a property that renders it desirable as an enzyme cofactor but dangerous as a source of free radicals. To regulate cellular Cu metabolism, an elaborate system of chaperones and transporters has evolved, although no human Cu chaperone mutations have been described to date. We describe a child from a consanguineous family who inherited homozygous mutations in the SLC33A1, encoding an acetyl CoA transporter, and in CCS, encoding the Cu chaperone for superoxide dismutase. The CCS mutation, p.Arg163Trp, predicts substitution of a highly conserved arginine residue at position 163, with tryptophan in domain II of CCS, which interacts directly with superoxide dismutase 1 (SOD1). Biochemical analyses of the patient's fibroblasts, mammalian cell transfections, immunoprecipitation assays, and Lys71 (CCS homolog) yeast complementation support the pathogenicity of the mutation. Expression of CCS was reduced and binding of CCS to SOD1 impaired. As a result, this mutation causes reduced SOD1 activity and may impair other mechanisms important for normal Cu homeostasis. CCS-Arg163Trp represents the primary example of a human mutation in a gene coding for a Cu chaperone. Hum Mutat 33:1207-1215. (c) 2012 Wiley Periodicals, Inc.
C1 [Huppke, Peter; Brendel, Cornelia; Gaertner, Jutta] Univ Gottingen, Dept Pediat & Pediat Neurol, Fac Med, D-37075 Gottingen, Germany.
[Korenke, Georg Christoph; Marquardt, Iris] Childrens Hosp, Dept Pediat Neurol, Oldenburg, Germany.
[Donsante, Anthony; Yi, Ling; Hicks, Julia D.; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD USA.
[Steinbach, Peter J.] NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Wilson, Callum] Starship Childrens Hosp, Natl Metab Serv, Auckland, New Zealand.
[Elpeleg, Orly] Hebrew Univ Jerusalem, Monique & Jacques Roboh Dept Genet Res, Med Ctr, Jerusalem, Israel.
[Elpeleg, Orly] Hebrew Univ Jerusalem, Med Ctr, Dept Genet & Metab Dis, Jerusalem, Israel.
[Moller, Lisbeth Birk] Kennedy Ctr, Ctr Appl Human Mol Genet, Glostrup, Denmark.
[Christodoulou, John] Childrens Hosp Westmead, Western Sydney Genet Program, Westmead, NSW, Australia.
[Christodoulou, John] Univ Sydney, Disciplines Pediat & Child Hlth, Sydney, NSW 2006, Australia.
[Christodoulou, John] Univ Sydney, Disciplines Genet Med, Sydney, NSW 2006, Australia.
RP Huppke, P (reprint author), Univ Gottingen, Dept Pediat & Pediat Neurol, Fac Med, Robert Koch Str 40, D-37075 Gottingen, Germany.
EM phuppke@med.uni-goettingen.de
RI Christodoulou, John/E-5866-2015;
OI Christodoulou, John/0000-0002-8431-0641
FU Intramural Research Program of the US National Institutes of Health
[HD008768-08]; German Research Foundation [GA 354/9-1]
FX Intramural Research Program of the US National Institutes of Health
(Project #HD008768-08) and the German Research Foundation (GA 354/9-1).
NR 40
TC 8
Z9 10
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD AUG
PY 2012
VL 33
IS 8
BP 1207
EP 1215
DI 10.1002/humu.22099
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 973QV
UT WOS:000306375800012
PM 22508683
ER
PT J
AU Li, F
Patterson, AD
Krausz, KW
Tanaka, N
Gonzalez, FJ
AF Li, Fei
Patterson, Andrew D.
Krausz, Kristopher W.
Tanaka, Naoki
Gonzalez, Frank J.
TI Metabolomics reveals an essential role for peroxisome
proliferator-activated receptor alpha in bile acid homeostasis
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE PPAR alpha; bile acid metabolism; phospholipid metabolism; cholesterol
and corticosterone metabolism
ID CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE; ORGANIC CATION TRANSPORTER;
FARNESOID-X-RECEPTOR; PPAR-ALPHA; MASS-SPECTROMETRY; RAT-LIVER; INDUCED
CHOLESTASIS; TUBULAR SECRETION; DOWN-REGULATION; HEPATITIS-B
AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear receptor that regulates fatty acid transport and metabolism. Previous studies revealed that PPAR alpha can affect bile acid metabolism; however, the mechanism by which PPAR alpha regulates bile acid homeostasis is not understood. In this study, an ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics approach was used to profile metabolites in urine, serum, and bile of wild-type and Ppara-null mice following cholic acid (CA) dietary challenge. Metabolomic analysis showed that the levels of several serum bile acids, such as CA (25-fold) and taurocholic acid (16-fold), were significantly increased in CA-treated Ppara-null mice compared with CA-treated wild-type mice. Phospholipid homeostasis, as revealed by decreased serum lysophosphatidylcholine (LPC) 16:0 (1.6-fold) and LPC 18:0 (1.6-fold), and corticosterone metabolism noted by increased urinary excretion of 11 beta-hydroxy-3,20-dioxopregn-4-en-21-oic acid (20-fold) and 11 beta,20 alpha-dihydroxy-3-oxo-pregn-4-en-21-oic acid (3.6-fold), were disrupted in CA-treated Ppara-null mice. The hepatic levels of mRNA encoding transporters Abcb11, Abcb4, Abca1, Abcg5, and Abcg8 were diminished in Ppara-null mice, leading to the accumulation of bile acids in the liver during the CA challenge.(jlr) These observations revealed that PPAR alpha is an essential regulator of bile acid biosynthesis, transport, and secretion.-Li, F., A. D. Patterson, K. W. Krausz, N. Tanaka, and F. J. Gonzalez. Metabolomics reveals an essential role for peroxisome proliferator-activated receptor alpha in bile acid homeostasis. J. Lipid Res. 2012. 53: 1625-1635.
C1 [Li, Fei; Patterson, Andrew D.; Krausz, Kristopher W.; Tanaka, Naoki; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012; Li, Fei/F-6849-2013
OI Patterson, Andrew/0000-0003-2073-0070;
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health.
NR 50
TC 21
Z9 23
U1 0
U2 17
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD AUG
PY 2012
VL 53
IS 8
BP 1625
EP 1635
DI 10.1194/jlr.M027433
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 973MT
UT WOS:000306364900021
PM 22665165
ER
PT J
AU Wadiwala, MF
Kamal, AK
AF Wadiwala, Muhammad Faisal
Kamal, Ayeesha Kamran
TI Extending the window for thrombolysis in acute stroke
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Vasc Fellowship Program, Fogarty Int Ctr, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv, Fogarty Int Ctr, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 1
TC 0
Z9 0
U1 1
U2 1
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD AUG
PY 2012
VL 62
IS 8
BP 858
EP 859
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 969IT
UT WOS:000306049600030
PM 23862270
ER
PT J
AU Atta, MG
Estrella, MM
Kuperman, M
Foy, MC
Fine, DM
Racusen, LC
Lucas, GM
Nelson, GW
Warner, AC
Winkler, CA
Kopp, JB
AF Atta, Mohamed G.
Estrella, Michelle M.
Kuperman, Michael
Foy, Matthew C.
Fine, Derek M.
Racusen, Lorraine C.
Lucas, Gregory M.
Nelson, George W.
Warner, Andrew C.
Winkler, Cheryl A.
Kopp, Jeffrey B.
TI HIV-associated nephropathy patients with and without apolipoprotein L1
gene variants have similar clinical and pathological characteristics
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE APOL1; end-stage kidney disease; HIV-associated nephropathy
ID STAGE RENAL-DISEASE; LIPID-BINDING PROTEIN; AUTOPHAGIC CELL-DEATH;
KIDNEY-DISEASE; INFECTED INDIVIDUALS; APOL1 VARIANTS; RISK;
SUSCEPTIBILITY; PROGRESSION
AB Recently, an association was found between nondiabetic kidney disease in African Americans and two independent sequence variants in the APOL1 gene, encoding apolipoprotein L1. In this study we determined the frequency of APOL1 risk variants in patients with biopsy-proven HIV-associated nephropathy (HIVAN) and distinctive pathological characteristics potentially driven by those risk variants. Among 76 patients with HIVAN, 60 were successfully genotyped for APOL1 G1 and G2 polymorphisms. In this cohort, 37 had two risk alleles, 18 were heterozygous, and 5 had neither risk variant. There were no differences in the pathological findings of HIVAN and the number of APOL1 risk alleles. Further, the progression to end-stage kidney disease or death did not differ by the number of risk alleles. Median renal survival was 9.3 months in patients with zero or one risk allele compared to 11.7 months in patients with two APOL1 risk alleles. Thus, our study suggests that although the majority of African-American patients with HIVAN have two APOL1 risk alleles other as yet unknown factors in the host, including genetic risk variants and environmental or viral factors, may influence the development of this disorder in those with zero or one APOL1 risk allele. Kidney International (2012) 82, 338-343; doi:10.1038/ki.2012.111; published online 11 April 2012
C1 [Atta, Mohamed G.; Estrella, Michelle M.; Foy, Matthew C.; Fine, Derek M.; Lucas, Gregory M.] Johns Hopkins Med Ctr, Dept Med, Baltimore, MD USA.
[Kuperman, Michael; Racusen, Lorraine C.] Johns Hopkins Med Ctr, Dept Pathol, Baltimore, MD USA.
[Warner, Andrew C.] NCI, Pathol Histotechnol Lab, Lab Anim Sci Program, Frederick, MD 21701 USA.
[Winkler, Cheryl A.] SAIC Frederick Inc, Basic Sci Program Ctr Canc Res, NCI, Frederick, MD USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
RP Atta, MG (reprint author), Johns Hopkins, Med, 1830 E Monument St,Suite 416, Baltimore, MD 21205 USA.
EM matta1@jhmi.edu
RI Lucas, Gregory/B-9225-2009;
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIDDK; NCI; National Cancer Institute, National Institutes of Health
[HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer
Research; NIH-NIDDK [P01DK056492, 1K23DK081317]; NIH [R01 DA026770];
National Cancer Institute; National Institute for Diabetes and Digestive
and Kidney Disease, NIH
FX This work was supported in part by the NIDDK and NCI Intramural Research
programs. This project has been funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under contract HHSN26120080001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
Research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. We thank
Paul Kimmel for critical review of the manuscript. MGA is supported by
the NIH-NIDDK grant P01DK056492, MME is supported by the NIH-NIDDK grant
1K23DK081317, and GML is supported by NIH grant R01 DA026770; this work
was supported by the Intramural Research Programs of the National Cancer
Institute and the National Institute for Diabetes and Digestive and
Kidney Disease, NIH.
NR 20
TC 20
Z9 21
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD AUG
PY 2012
VL 82
IS 3
BP 338
EP 343
DI 10.1038/ki.2012.111
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 973OV
UT WOS:000306370500013
PM 22495294
ER
PT J
AU Hu, HH
Bornert, P
Hernando, D
Kellman, P
Ma, JF
Reeder, S
Sirlin, C
AF Hu, Houchun Harry
Boernert, Peter
Hernando, Diego
Kellman, Peter
Ma, Jingfei
Reeder, Scott
Sirlin, Claude
TI ISMRM workshop on fat-water separation: Insights, applications and
progress in MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE water-fat imaging; fat-water separation; Dixon; chemical-shift; fat
quantification
ID STATE FREE PRECESSION; BROWN ADIPOSE-TISSUE; LOCALIZED PROTON
SPECTROSCOPY; FIELD MAP ESTIMATION; H-1-MAGNETIC RESONANCE SPECTROSCOPY;
INITIAL CLINICAL-EXPERIENCE; 3-POINT DIXON TECHNIQUE;
SICKLE-CELL-DISEASE; MAGNETIC-RESONANCE; STEADY-STATE
AB Approximately 130 attendees convened on February 1922, 2012 for the first ISMRM-sponsored workshop on waterfat imaging. The motivation to host this meeting was driven by the increasing number of research publications on this topic over the past decade. The scientific program included an historical perspective and a discussion of the clinical relevance of waterfat MRI, a technical description of multiecho pulse sequences, a review of data acquisition and reconstruction algorithms, a summary of the confounding factors that influence quantitative fat measurements and the importance of MRI-based biomarkers, a description of applications in the heart, liver, pancreas, abdomen, spine, pelvis, and muscles, an overview of the implications of fat in diabetes and obesity, a discussion on MR spectroscopy, a review of childhood obesity, the efficacy of lifestyle interventional studies, and the role of brown adipose tissue, and an outlook on federal funding opportunities from the National Institutes of Health. Magn Reson Med, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Hu, Houchun Harry] Univ So Calif, Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA.
[Hu, Houchun Harry] Univ So Calif, Childrens Hosp Los Angeles, Dept Elect Engn, Los Angeles, CA 90027 USA.
[Boernert, Peter] Philips Res Labs, Hamburg, Germany.
[Hernando, Diego; Reeder, Scott] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Ma, Jingfei] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA.
[Sirlin, Claude] Univ Calif San Diego, Dept Radiol, Liver Imaging Grp, San Diego, CA 92103 USA.
RP Hu, HH (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Dept Radiol, Mail Stop 81,4650 Sunset Blvd, Los Angeles, CA 90027 USA.
EM houchunh@usc.edu
RI Giunta, Gaetano/G-4333-2012;
OI Giunta, Gaetano/0000-0002-1514-2576; Sirlin, Claude/0000-0002-6639-9072;
Reeder, Scott/0000-0003-4728-8171
FU GE Healthcare; Philips Healthcare; Toshiba America Medical Systems
FX Grant sponsors: GE Healthcare, Philips Healthcare, Toshiba America
Medical Systems.
NR 159
TC 43
Z9 44
U1 0
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD AUG
PY 2012
VL 68
IS 2
BP 378
EP 388
DI 10.1002/mrm.24369
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 972YZ
UT WOS:000306318900009
PM 22693111
ER
PT J
AU Brimberg, L
Benhar, I
Mascaro-Blanco, A
Alvarez, K
Lotan, D
Winter, C
Klein, J
Moses, AE
Somnier, FE
Leckman, JF
Swedo, SE
Cunningham, MW
Joel, D
AF Brimberg, Lior
Benhar, Itai
Mascaro-Blanco, Adita
Alvarez, Kathy
Lotan, Dafna
Winter, Christine
Klein, Julia
Moses, Allon E.
Somnier, Finn E.
Leckman, James F.
Swedo, Susan E.
Cunningham, Madeleine W.
Joel, Daphna
TI Behavioral, Pharmacological, and Immunological Abnormalities after
Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related
Neuropsychiatric Disorders
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE streptococcus group A (GAS); Sydenham chorea (SC); PANDAS; dopamine;
animal model; autoimmunity
ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA; TOURETTES-SYNDROME;
GROOMING BEHAVIOR; RHEUMATIC-FEVER; NERVOUS-SYSTEM; ANIMAL-MODEL;
M-PROTEINS; ANTIBODIES; PANDAS
AB Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. Neuropsychopharmacology (2012) 37, 2076-2087; doi:10.1038/npp.2012.56; published online 25 April 2012
C1 [Cunningham, Madeleine W.] Univ Oklahoma, Hlth Sci Ctr, Biomed Res Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
[Brimberg, Lior; Lotan, Dafna; Joel, Daphna] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Benhar, Itai] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel.
[Winter, Christine] Tech Univ Dresden, Dept Psychiat, D-01062 Dresden, Germany.
[Winter, Christine; Klein, Julia] Charite, Dept Psychiat, D-13353 Berlin, Germany.
[Moses, Allon E.] Hadassah Univ Hosp, Dept Clin Microbiol & Infect Dis, IL-91120 Jerusalem, Israel.
[Somnier, Finn E.] Statens Serum Inst, Dept Clin Biochem & Immunol, DK-2300 Copenhagen, Denmark.
[Leckman, James F.] Yale Univ, Sch Med, Dept Pediat, Yale Child Study Ctr, New Haven, CT 06510 USA.
[Leckman, James F.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
RP Cunningham, MW (reprint author), Univ Oklahoma, Hlth Sci Ctr, Biomed Res Ctr, Dept Microbiol & Immunol, 975 NE 10th St, Oklahoma City, OK 73104 USA.
EM madeleine-cunningham@ouhsc.edu
FU Israel Science Foundation Grant [341/07]; ADAMS Super Center for Brain
Studies at Tel Aviv University; NIH MERIT AWARD [NIH-R37HL35280,
NIH-R01HL56267]; Oklahoma Center for the Advancement of Science and
Technology (OCAST); PANDAS Research Fund at the NIMH Bench to Bedside
grant; Grifols; NIH [NIH-R01MH061940, NIH-P01MH049351, NIH-K05MH076273];
[NIH-5R25MH077823]
FX We thank Professor D Michaelson (Department of Neurobiology, Tel-Aviv
University, Israel) for helpful discussions and immunohistochemical
assistance, Dr Christine Kirvan (California State University at
Sacramento, Ca) for hepful discussions, and Reinhard Sohr (at the
University Medicine Charite, Berlin, Germany) for the biochemistry
analysis. We express gratitude to all of the parents who donated funds
to our project. This work was funded in part by the Israel Science
Foundation Grant 341/07 to DJ and ADAMS Super Center for Brain Studies
at Tel Aviv University to DJ; in part by NIH-R37HL35280 (NIH MERIT
AWARD) and NIH-R01HL56267 to MWC; in part by the Oklahoma Center for the
Advancement of Science and Technology (OCAST) to MWC; in part by the
PANDAS Research Fund at the NIMH Bench to Bedside grant to JFL, MWC,and
SES; and in part by NIH-5R25MH077823 and Grifols (formerly Talecris
Biotherapeutics) to JFL. The human specimens from Yale University were
collected as part of the NIH-Funded grants to JFL (NIH-R01MH061940,
NIH-P01MH049351, and NIH-K05MH076273.
NR 61
TC 54
Z9 54
U1 1
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD AUG
PY 2012
VL 37
IS 9
BP 2076
EP 2087
DI 10.1038/npp.2012.56
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 975FY
UT WOS:000306494600010
PM 22534626
ER
PT J
AU Kraus, SR
Lemack, G
Chai, T
Sirls, L
Lloyd, K
Norton, P
Mueller, E
Menefee, S
Shepherd, J
Kusek, J
Litman, H
AF Kraus, S. R.
Lemack, G.
Chai, T.
Sirls, L.
Lloyd, K.
Norton, P.
Mueller, E.
Menefee, S.
Shepherd, J.
Kusek, J.
Litman, H.
TI COMPARISON OF URODYNAMIC CHANGES BETWEEN AUTOLOGOUS FASCIA PUBOVAGINAL
SLING AND SYNTHETIC MIDURETHRAL SLING
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the International-Continence-Society (ICS)
CY OCT 15-19, 2012
CL Beijing, PEOPLES R CHINA
SP Int Continence Soc
ID BURCH COLPOSUSPENSION
C1 [Kraus, S. R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
[Lemack, G.] Univ Texas SW, Dallas, TX USA.
[Chai, T.] Univ Maryland, Baltimore, MD 21201 USA.
[Sirls, L.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Lloyd, K.] Univ Alabama Birmingham, Birmingham, AL USA.
[Norton, P.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Mueller, E.] Loyola Med Ctr, Maywood, IL USA.
[Menefee, S.] Univ Calif San Diego, Med Ctr, Kaiser Permanente, San Diego, CA 92103 USA.
[Shepherd, J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kusek, J.] NIDDK, Bethesda, MD USA.
[Litman, H.] New England Res Inst, Watertown, MA 02172 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PD AUG
PY 2012
VL 31
IS 6
MA 252
BP 1053
EP 1054
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 972XM
UT WOS:000306314700253
ER
PT J
AU Morehead-Gee, AJ
Pfalzer, L
Levy, E
McGarvey, C
Springer, B
Soballe, P
Gerber, L
Stout, NL
AF Morehead-Gee, Alicia J.
Pfalzer, Lucinda
Levy, Ellen
McGarvey, Charles
Springer, Barbara
Soballe, Peter
Gerber, Lynn
Stout, Nicole L.
TI Racial disparities in physical and functional domains in women with
breast cancer
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Breast cancer; Health status; Health-related quality of life; Race;
Physical impairment; Health disparities
ID QUALITY-OF-LIFE; AXILLARY WEB SYNDROME; PREOPERATIVE ASSESSMENT ENABLES;
SF-36 HEALTH SURVEY; SOCIOECONOMIC-STATUS; AFRICAN-AMERICAN; ARM
LYMPHEDEMA; WHITE WOMEN; ETHNIC DISPARITIES; EARLY-DIAGNOSIS
AB African-American women are more likely than white women to have functional impairments after breast cancer (BC) surgery; however, no differences were found in self-reported health status surveys at 12+ months postsurgery.
This analysis compared white and African-American BC survivors' (BCS) health status, health-related quality of life, and the occurrence of physical impairments after BC treatment.
One hundred sixty-six women (130 white, 28 African-American, 8 other) were assessed for impairments preoperatively and at 1, 3, 6, 9, and 12+ months postsurgery. Health status was assessed at 12+ months using the Short Form Health Survey (SF36v2 (TM)). Analysis of variance estimated differences between groups for health status and impairment occurrence.
No differences were found between groups for BC type, stage, grade, or tumor size; surgery type; or number of lymph nodes sampled. African-American BCS had more estrogen/progesterone receptor-negative tumors (p < 0.001; p = 0.036) and received radiation more frequently (p = 0.03). More African-American BCS were employed (p = 0.022) and reported higher rates of social activities (p = 0.011) but less recreational activities (p = 0.020) than white BCS. African-American BCS had higher rates of cording (p = 0.013) and lymphedema (p = 0.011) postoperatively. No differences were found in self-reported health status.
In a military healthcare system, where access to care is ubiquitous, there were no significant differences in many BC characteristics commonly attributed to race. African-American women had more ER/PR-negative tumors; however, no other BC characteristics differed between racial groups. African-American women exhibited more physical impairments, although their BC treatment only differed regarding radiation therapy. This suggests that African-American BCS may be at higher risk for physical impairments and should be monitored prospectively for early identification and treatment.
C1 [Stout, Nicole L.] Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD 20889 USA.
[Morehead-Gee, Alicia J.; Levy, Ellen] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pfalzer, Lucinda] Univ Michigan, Phys Therapy Dept, Flint, MI 48503 USA.
[McGarvey, Charles] CLM Consulting, Rockville, MD USA.
[Springer, Barbara] USA, Off Surg Gen, Rehabil & Reintegrat Div, Falls Church, VA USA.
[Soballe, Peter] USN Hosp, San Diego, CA 92134 USA.
[Gerber, Lynn] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA.
RP Stout, NL (reprint author), Natl Naval Med Ctr, Breast Care Ctr, 8901 Wisconsin Ave,Bldg 19,3rd Floor, Bethesda, MD 20889 USA.
EM Nicole.stout@med.navy.mil
FU National Naval Medical Center (National Naval Medical Center [NNMC])
[NNMC 2001-052]; National Institutes of Health (NIH), Clinical Center,
Rehabilitation Medicine Department, Physical Therapy Section [NIH
02-CC-0044]
FX This study was supported by the National Naval Medical Center (National
Naval Medical Center [NNMC] Protocol NNMC 2001-052) and by the National
Institutes of Health (NIH), Clinical Center, Rehabilitation Medicine
Department, Physical Therapy Section (Protocol NIH 02-CC-0044).
NR 48
TC 7
Z9 7
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD AUG
PY 2012
VL 20
IS 8
BP 1839
EP 1847
DI 10.1007/s00520-011-1285-7
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 970LG
UT WOS:000306129600030
PM 21979903
ER
PT J
AU Morris, BA
Chambers, SK
Campbell, M
Dwyer, M
Dunn, J
AF Morris, B. A.
Chambers, S. K.
Campbell, M.
Dwyer, M.
Dunn, J.
TI Motorcycles and breast cancer: The influence of peer support and
challenge on distress and posttraumatic growth
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Cancer; Distress; Posttraumatic growth; Social comparison; Social
identity
ID QUALITY-OF-LIFE; GROUP COHESION; SURVIVORS; EXERCISE; WOMEN; STRESS;
EXPERIENCES; INVENTORY; PROGRAMS; IDENTITY
AB Peer support programs based on exercise or challenge activities may have potential to improve well-being for women diagnosed with breast cancer. The current study investigated the role of social comparison and social identity based on group membership on posttraumatic growth (PTG) and distress.
Fifty-one women diagnosed with breast cancer who participated in a 1,000 mi group motorcycle ride completed pre- and post-ride surveys. Participants had a mean age of 49.82 years (SD = 7.04) and their average time since diagnosis was 6.39 years (SD = 3.89).
Cancer-related distress significantly decreased after the ride. PTG did not significantly differ after the ride, which may have been a result of a ceiling effect on this measure. Hierarchical regression analyses showed that pre-ride PTG (p < 0.01) and upward social comparison during the ride (p < 0.05) were related to post-ride PTG. Pre-ride distress was the only variable to remain significantly related to post-ride distress (p < 0.01).
The results of the current study highlight the potential for challenge-based activities to provide a positive peer support environment for women diagnosed with breast cancer. Identifying factors that promote personal growth and reduce cancer-related distress allow us to create a model for the delivery of these challenge-based peer support activities.
C1 [Morris, B. A.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Chambers, S. K.; Dunn, J.] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia.
[Chambers, S. K.; Dunn, J.] Griffith Univ, Griffith Hlth Inst, Gold Coast, Australia.
[Campbell, M.; Dwyer, M.] Amazon Heart, Brisbane, Qld, Australia.
[Dunn, J.] Univ Queensland, Sch Social Sci, St Lucia, Qld, Australia.
RP Morris, BA (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bldg 31,Room B1B36,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA.
EM morrisba@mail.nih.gov
RI Chambers, Suzanne/H-5957-2012; Dunn, Jeff/H-6002-2012
FU Cancer Council Queensland
FX This project was funded by the Cancer Council Queensland. We thank all
the Amazon Heart women who generously agreed to take part in this
project.
NR 40
TC 3
Z9 4
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD AUG
PY 2012
VL 20
IS 8
BP 1849
EP 1858
DI 10.1007/s00520-011-1287-5
PG 10
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 970LG
UT WOS:000306129600031
PM 21983863
ER
PT J
AU Yang, Q
He, X
Yang, L
Zhou, ZY
Cullinane, AR
Wei, AH
Zhang, Z
Hao, ZH
Zhang, AL
He, M
Feng, YQ
Gao, X
Gahl, WA
Huizing, M
Li, W
AF Yang, Qing
He, Xin
Yang, Lin
Zhou, Zhiyong
Cullinane, Andrew R.
Wei, Aihua
Zhang, Zhe
Hao, Zhenhua
Zhang, Aili
He, Min
Feng, Yaqin
Gao, Xiang
Gahl, William A.
Huizing, Marjan
Li, Wei
TI The BLOS1-Interacting Protein KXD1 is Involved in the Biogenesis of
Lysosome-Related Organelles
SO TRAFFIC
LA English
DT Article
DE BLOC-1; BLOS1; Hermansky-Pudlak syndrome; KXD1; lysosome-related
organelles
ID HERMANSKY-PUDLAK-SYNDROME; STORAGE POOL DEFICIENCY; COMPLEX-1 BLOC-1;
MOUSE MODEL; DYSBINDIN; GENE; TRAFFICKING; ENCODES; SNAPIN; PIGMENTATION
AB Biogenesis of lysosome-related organelles (LROs) complex-1 (BLOC-1) is an eight-subunit complex involved in lysosomal trafficking. Interacting proteins of these subunits expand the understanding of its biological functions. With the implementation of the naive Bayesian analysis, we found that a human uncharacterized 20 kDa coiled-coil KxDL protein, KXD1, is a BLOS1-interacting protein. In vitro binding assays confirmed the interaction between BLOS1 and KXD1. The mouse KXD1 homolog was widely expressed and absent in Kxd1 knockout (KO) mice. BLOS1 was apparently reduced in Kxd1-KO mice. Mild defects in the melanosomes of the retinal pigment epithelia and in the platelet dense granules of the Kxd1-KO mouse were observed, mimicking a mouse model of mild HermanskyPudlak syndrome that affects the biogenesis of LROs.
C1 [Yang, Qing; He, Xin; Yang, Lin; Zhou, Zhiyong; Zhang, Zhe; Hao, Zhenhua; Zhang, Aili; He, Min; Feng, Yaqin; Li, Wei] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China.
[Yang, Qing; Zhang, Zhe; Hao, Zhenhua; Zhang, Aili] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China.
[Cullinane, Andrew R.; Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Wei, Aihua] Capital Med Univ, Beijing Tongren Hosp, Dept Dermatol, Beijing 100730, Peoples R China.
[Gao, Xiang] Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing 210061, Jiangsu, Peoples R China.
RP Li, W (reprint author), Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China.
EM xhe@genetics.ac.cn; wli@genetics.ac.cn
FU National Natural Science Foundation of China [31071252, 81101182,
30730049]; Ministry of Agriculture of PRC [2009ZX08009-158B]; Chinese
Academy of Sciences [KSCX2-EW-R-05]; National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA
FX This work was partially supported by grants from National Natural
Science Foundation of China (31071252; 81101182; 30730049), Ministry of
Agriculture of PRC (2009ZX08009-158B), Chinese Academy of Sciences
(KSCX2-EW-R-05) and the Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA. We thank Dr Xinquan Wang at Tsinghua University for
support in the co-fractionation assay, Drs Shosuke Ito and Kazumasa
Wakamatsu for providing the protocol and reagents of melanin analysis
and we are thankful to Dr Michael Marks at University of Pennsylvania
for his critical comments to our manuscript.
NR 42
TC 17
Z9 20
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD AUG
PY 2012
VL 13
IS 8
BP 1160
EP 1169
DI 10.1111/j.1600-0854.2012.01375.x
PG 10
WC Cell Biology
SC Cell Biology
GA 973MR
UT WOS:000306364700012
PM 22554196
ER
PT J
AU Goldstein, RB
Dawson, DA
Smith, SM
Grant, BF
AF Goldstein, R. B.
Dawson, D. A.
Smith, S. M.
Grant, B. F.
TI Antisocial behavioral syndromes and 3-year quality-of-life outcomes in
United States adults
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE antisocial personality disorder; quality of life; epidemiology;
longitudinal course
ID NATIONAL EPIDEMIOLOGIC SURVEY; BORDERLINE PERSONALITY-DISORDER; DRUG-USE
DISORDERS; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; CONDUCT DISORDER;
SEX-DIFFERENCES; FOLLOW-UP; SOCIAL COMPETENCE; 10-YEAR COURSE
AB Goldstein RB, Dawson DA, Smith SM, Grant BF. Antisocial behavioral syndromes and 3-year quality-of-life outcomes in United States adults. Objective: To examine 3-year quality-of-life (QOL) outcomes among United States adults with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) antisocial personality disorder (ASPD), syndromal adult antisocial behavior without conduct disorder (CD) before age 15 [adulthood antisocial behavioral syndrome (AABS), not a DSM-IV diagnosis], or no antisocial behavioral syndrome at baseline. Method: Face-to-face interviews (n = 34 653). Psychiatric disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV Version. Health-related QOL was assessed using the Short-Form 12-Item Health Survey, version 2 (SF-12v2). Other outcomes included past-year Perceived Stress Scale-4 (PSS-4) scores, employment, receipt of Supplemental Security Income (SSI), welfare, and food stamps, and participation in social relationships. Results: Antisocial personality disorder and AABS predicted poorer employment, financial dependency, social relationship, and physical health outcomes. Relationships of antisociality to SSI and food stamp receipt and physical health scales were modified by baseline age. Both antisocial syndromes predicted higher PSS-4, AABS predicted lower SF-12v2 Vitality, and ASPD predicted lower SF-12v2 Social Functioning scores in women. Conclusion: Similar prediction of QOL by ASPD and AABS suggests limited utility of requiring CD before age 15 to diagnose ASPD. Findings underscore the need to improve prevention and treatment of antisocial syndromes.
C1 [Goldstein, R. B.; Dawson, D. A.; Smith, S. M.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3071,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM goldster@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institutes of Health, NIAAA
FX The National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC) is funded by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) with supplemental support from the National Institute
on Drug Abuse. This research was supported in part by the Intramural
Program of the National Institutes of Health, NIAAA. Dr. Rise B.
Goldstein had full access to all of the data in this study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis.
NR 87
TC 6
Z9 6
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0001-690X
EI 1600-0447
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD AUG
PY 2012
VL 126
IS 2
BP 137
EP 150
DI 10.1111/j.1600-0447.2012.01848.x
PG 14
WC Psychiatry
SC Psychiatry
GA 970IO
UT WOS:000306121800007
PM 22375904
ER
PT J
AU Vyas, NS
Lee, Y
Ahn, K
Ternouth, A
Stahl, DR
Al-Chalabi, A
Powell, JF
Puri, BK
AF Vyas, Nora S.
Lee, Yohan
Ahn, Kwangmi
Ternouth, Andrew
Stahl, Daniel R.
Al-Chalabi, Ammar
Powell, John F.
Puri, Basant K.
TI Association of a Serotonin Receptor 2A Gene Polymorphism with Visual
Sustained Attention in Early-Onset Schizophrenia Patients and their
Non-Psychotic Siblings
SO AGING AND DISEASE
LA English
DT Article
DE adolescence; attention; biological relatives; gene polymorphism; T102C;
HTR2A; Schizophrenia
AB The serotonin receptor 2A gene polymorphism is associated with attentional processes in schizophrenia. However, the specificity of the underlying cognitive constructs affected within this domain requires further elucidation. We carried out the first investigation of whether the TC/CC genotype of the 5-HT2A T102C polymorphism confers impairments in early-onset schizophrenia (EOS; onset of psychotic symptoms before age 18) but not in healthy siblings, the putative mechanism being that serotonergic inhibitory modulation of prefrontal dopamine is impaired in the presence of the C allele which in turn is a genetic risk marker for schizophrenia. Fifty-three EOS outpatients and 46 of their non-psychotic siblings (no current Axis I diagnoses) were genotyped for 5-HT2A T102C polymorphism. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptomatology severity. Diagnostic classification was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Structured Clinical Interview. The Degraded-Stimulus Continuous Performance Test (DS-CPT) was used to measure sustained focused attention. As predicted, EOS probands produced fewer correct responses (hit rate) and demonstrated poorer perceptual sensitivity compared with the healthy siblings. The C allele at codon 102 was associated with fewer correct responses compared with the TT genotype. There was no significant relationship between the polymorphism and clinical parameters, as measured using the PANSS. Our findings suggest that the C allele may be related to sustained attentional impairments in EOS.
C1 [Vyas, Nora S.; Lee, Yohan; Ahn, Kwangmi] NIMH, Child Psychiat Branch, NIH, Bethesda, MD USA.
[Vyas, Nora S.; Ternouth, Andrew] Kings Coll London, MRC, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Vyas, Nora S.; Ternouth, Andrew] Kings Coll London, Dept Psychosis Studies, Inst Psychiat, London WC2R 2LS, England.
[Stahl, Daniel R.] Kings Coll London, Dept Biostat & Comp, Inst Psychiat, London WC2R 2LS, England.
[Al-Chalabi, Ammar; Powell, John F.] Kings Coll London, Dept Clin Neurosci, Inst Psychiat, MRC,Ctr Neurodegenerat Res, London WC2R 2LS, England.
[Puri, Basant K.] Univ London Imperial Coll Sci Technol & Med, Dept Imaging, Hammersmith Hosp, London SW7 2AZ, England.
[Puri, Basant K.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England.
RP Vyas, NS (reprint author), NIMH, Child Psychiat Branch, NIH, Bethesda, MD USA.
EM nora.vyas@nih.gov
RI Stahl, Daniel/B-9713-2011
OI Stahl, Daniel/0000-0001-7987-6619
FU departmental fund at King's College London, Institute of Psychiatry,
London, UK; Fulbright Distinguished Scholar Award by the US-UK Fulbright
Commission; Motor Neurone Disease of Great Britain; Motor Neurone
Disease of Northern Ireland; ALS Association; NIHR specialist Biomedical
Research Centre for Mental Health at the South London; Maudsley NHS
Foundation Trust; Institute of Psychiatry, King's College London;
European Community [259867]
FX We would like to thank all families who contributed to the VIPS study.
This work was supported by a departmental fund at King's College London,
Institute of Psychiatry, London, UK. We are very grateful to Professors
Sophia Frangou and David A Collier for their research supervision, and
useful comments on earlier drafts of this manuscript. We thank Dr Armin
Raznahan (Child Psychiatry Branch, National Institutes of Health) for
his useful comments on our manuscript. We would also like to thank Dr
Lisa Burke for conducting the clinical interviews in this study.; NSV is
supported by the Fulbright Distinguished Scholar Award by the US-UK
Fulbright Commission. AAC thanks the Motor Neurone Disease of Great
Britain and Northern Ireland and the ALS Association for support. We
thank the NIHR specialist Biomedical Research Centre for Mental Health
at the South London and Maudsley NHS Foundation Trust (SLaM) and the
Institute of Psychiatry, King's College London. The research leading to
results (ALS) has received funding from the European Community's Health
Seventh Framework Programme (FP7/2007-2013) under grant agreement no.
259867.
NR 65
TC 9
Z9 11
U1 6
U2 8
PU INT SOC AGING & DISEASE
PI FORT WORTH
PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA
SN 2152-5250
J9 AGING DIS
JI Aging Dis.
PD AUG
PY 2012
VL 3
IS 4
BP 291
EP 300
PG 10
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA V32KY
UT WOS:000208951300001
PM 23185710
ER
PT J
AU Wester, CW
Eden, SK
Shepherd, BE
Bussmann, H
Novitsky, V
Samuels, DC
Hendrickson, SL
Winkler, CA
O'Brien, SJ
Essex, M
D'Aquila, RT
deGruttola, V
Marlink, RG
AF Wester, C. William
Eden, Svetlana K.
Shepherd, Bryan E.
Bussmann, Hermann
Novitsky, Vladimir
Samuels, David C.
Hendrickson, Sher L.
Winkler, Cheryl A.
O'Brien, Stephen J.
Essex, Max
D'Aquila, Richard T.
deGruttola, Victor
Marlink, Richard G.
TI Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among
Combination Antiretroviral Therapy-Treated Adults in Botswana: Results
from a Clinical Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HIV-INFECTED PATIENTS; MITOCHONDRIAL TOXICITY; MANAGEMENT; NEVIRAPINE;
LAMIVUDINE; STAVUDINE; WOMEN
AB Nucleoside analogue reverse transcriptase inhibitors are an integral component of combination antiretroviral treatment regimens. However, their ability to inhibit polymerase-c has been associated with several mitochondrial toxicities, including potentially life-threatening lactic acidosis. A total of 650 antiretroviral-naive adults (69% female) initiated combination antiretroviral therapy (cART) and were intensively screened for toxicities including lactic acidosis as part of a 3-year clinical trial in Botswana. Patients were categorized as no lactic acidosis symptoms, minor symptoms but lactate <4.4 mmol/liter, and symptoms with lactate >= 4.4 mmol/liter [moderate to severe symptomatic hyperlactatemia (SH) or lactic acidosis (LA)]. Of 650 participants 111 (17.1%) developed symptoms and/or laboratory results suggestive of lactic acidosis and had a serum lactate drawn; 97 (87.4%) of these were female. There were 20 events, 13 having SH and 7 with LA; all 20 (100%) were female (p < 0.001). Cox proportional hazard analysis limited to the 451 females revealed that having a higher baseline BMI was predictive for the development of SH/LA [aHR = 1.17 per one-unit increase (1.08-1.25), p < 0.0001]. Ordered logistic regression performed among all 650 patients revealed that having a lower baseline hemoglobin [aOR = 1.28 per one-unit decrease (1.1-1.49), p = 0.002] and being randomized to d4T/3TC-based cART [aOR = 1.76 relative to ZDV/3TC (1.03-3.01), p = 0.04] were predictive of the symptoms and/or the development of SH/LA. cART-treated women in sub-Saharan Africa, especially those having higher body mass indices, should receive additional monitoring for SH/LA. Women presently receiving d4T/3TC-based cART in such settings also warrant more intensive monitoring.
C1 [Wester, C. William] Vanderbilt Univ, Sch Med, Div Infect Dis, Med Ctr N,VIGH,Dept Med, Nashville, TN 37232 USA.
[Wester, C. William; Bussmann, Hermann; Novitsky, Vladimir; Essex, Max; deGruttola, Victor; Marlink, Richard G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bussmann, Hermann; Novitsky, Vladimir; Essex, Max; Marlink, Richard G.] Botswana Harvard Univ, AIDS Initiat Partnership HIV Res & Educ BHP, Sch Publ Hlth, Gaborone, Botswana.
[Samuels, David C.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Hendrickson, Sher L.; Winkler, Cheryl A.; O'Brien, Stephen J.] SAIC Frederick Inc, Natl Canc Inst, Lab Genom Divers, Frederick, MD USA.
RP Wester, CW (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Med Ctr N,VIGH,Dept Med, 1161 21st Ave S,A-2200, Nashville, TN 37232 USA.
EM william.wester@vanderbilt.edu
RI Samuels, David/C-1365-2012; Samuels, David/A-5393-2008
OI Samuels, David/0000-0003-3529-7791
FU National Institute of Allergy and Infectious Diseases [K23AI073141];
grant evaluating Risk Factors for the Development of Lactic Acidosis and
Pancreatitis in Botswana; Harvard Center for AIDS Research (CFAR);
Vanderbilt-Meharry CFAR [P30AI54999]; [P30AI 060354]
FX The project described was also supported by the following research
grants from the National Institute of Allergy and Infectious Diseases:
K23AI073141 (PI: C. William Wester, M. D., M. P. H.) grant evaluating
Risk Factors for the Development of Lactic Acidosis and Pancreatitis in
Botswana and P30AI 060354 (PI: C. WilliamWester, M. D., M. P. H.),
Harvard Center for AIDS Research (CFAR) grant evaluating the Risk
Factors for the Development of Nevirapine-Associated Toxicity in
Southern Africa. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institute of Allergy and Infectious Diseases or the National Institutes
of Health. In addition, we also formally acknowledge the
Vanderbilt-Meharry CFAR grant (Grant P30AI54999) that supported the work
of Vanderbilt University School of Medicine senior statistician Bryan E.
Shepherd.
NR 24
TC 8
Z9 8
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD AUG
PY 2012
VL 28
IS 8
BP 759
EP 765
DI 10.1089/aid.2011.0303
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 977SA
UT WOS:000306683600004
PM 22540188
ER
PT J
AU Shebl, FM
Yu, K
Landgren, O
Goedert, JJ
Rabkin, CS
AF Shebl, Fatma M.
Yu, Kai
Landgren, Ola
Goedert, James J.
Rabkin, Charles S.
TI Increased Levels of Circulating Cytokines with HIV-Related
Immunosuppression
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY;
HOMOSEXUAL-MEN; VIRAL LOAD; INFECTION; INDIVIDUALS; LYMPHOCYTES;
INDUCTION; RESPONSES; VIREMIA
AB Cytokines may contribute to the severity of CD4 cell depletion with human immunodeficiency virus (HIV) infection, but quantitative relationships are not well defined. Serum and plasma from 181 HIV-infected individuals were tested with Millipore 30-plex Luminex cytokine assays. Within-individual correlations among cytokines were summarized by two-dimensional hierarchical cluster analysis. Associations with age, sex, race, CD4 count, and HIV viral load were determined with linear regression models. Tests for statistical significance were corrected for multiple comparisons, using a false discovery rate of 0.1. African-Americans had significantly higher levels than whites of six cytokines (IL-2, IL-5, IL-7, IL-15, fractalkine, and IFN-gamma), and lower levels of MCP-1. Females had higher fractalkine levels than males. Age was not associated with levels of any cytokine. Six cytokines, including the T-helper (Th) type 1 cytokine IL-15, the Th2 cytokines IL-1ra and IL-10, the chemokines fractalkine and MCP-1, and the growth factor G-CSF were each inversely associated with CD4 count; no cytokine was directly associated with CD4 count. Fractalkine was directly associated with HIV viral load, adjusted for CD4 count. Cytokines clustered by primary function (e. g., Th1, Th2, proinflammatory, chemokines, or growth factors) whereas individuals clustered according to cytokine levels (generally high, intermediate, or low) had significantly different CD4 counts [medians (interquartile range) of 60 (17-162), 131 (62-321), and 155 (44-467), respectively; p < 0.0001]. CD4 deficiency is associated with generalized increases in cytokines of various functions. Racial differences in cytokine response to HIV infection could contribute to disparities in disease progression.
C1 [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20852 USA.
[Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH,US Dept HHS, Rockville, MD 20852 USA.
RP Shebl, FM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 6120 Execut Blvd,EPS 7074, Rockville, MD 20852 USA.
EM fshebl@gmail.com
FU National Cancer Institute
FX We would like to thank Dr. Eric Engels for his helpful suggestions on a
previous version of this manuscript. This study was funded by the
Intramural Research Program of the National Cancer Institute.
NR 32
TC 11
Z9 11
U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD AUG
PY 2012
VL 28
IS 8
BP 809
EP 815
DI 10.1089/aid.2011.0144
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 977SA
UT WOS:000306683600012
PM 21962239
ER
PT J
AU Laeyendecker, O
Brookmeyer, R
Oliver, AE
Mullis, CE
Eaton, KP
Mueller, AC
Jacobson, LP
Margolick, JB
Brown, J
Rinaldo, CR
Quinn, TC
Eshleman, SH
AF Laeyendecker, Oliver
Brookmeyer, Ron
Oliver, Amy E.
Mullis, Caroline E.
Eaton, Kevin P.
Mueller, Amy C.
Jacobson, Lisa P.
Margolick, Joseph B.
Brown, Joelle
Rinaldo, Charles R.
Quinn, Thomas C.
Eshleman, Susan H.
CA MACS
TI Factors Associated with Incorrect Identification of Recent HIV Infection
Using the BED Capture Immunoassay
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENZYME-IMMUNOASSAY; IGG; ASSAY;
IMMUNOGLOBULIN; SEROCONVERSION; PERFORMANCE; CHALLENGES; AFRICA; COUNTS
AB The BED capture enzyme immunoassay (BED-CEIA) was developed for estimating HIV incidence from cross-sectional data. This assay misclassifies some individuals with nonrecent HIV infection as recently infected, leading to overestimation of HIV incidence. We analyzed factors associated with misclassification by the BED-CEIA. We analyzed samples from 383 men who were diagnosed with HIV infection less than 1 year after a negative HIV test (Multicenter AIDS Cohort Study). Samples were collected 2-8 years after HIV seroconversion, which was defined as the midpoint between the last negative and first positive HIV test. Samples were analyzed using the BED-CEIA with a cutoff of OD-n <= 0.8 for recent infection. Logistic regression was used to identify factors associated with misclassification. Ninety-one (15.1%) of 603 samples were misclassified. In multivariate models, misclassification was independently associated with highly active antiretroviral treatment (HAART) for >2 years, HIV RNA <400 copies/ml, and CD4 cell count <50 or <200 cells/mm(3); adjusted odds ratios (OR) and 95% confidence intervals (CI) were 4.72 (1.35-16.5), 3.96 (1.53-10.3), 6.85 (2.71-17.4), and 11.5 (3.64-36.0), respectively. Among 220 men with paired samples, misclassification 2-4 years after seroconversion was significantly associated with misclassification 6-8 years after seroconversion [adjusted OR: 25.8 (95% CI: 8.17-81.5), p < 0.001] after adjusting for race, CD4 cell count, HIV viral load, and HAART use. Low HIV viral load, low CD4 cell count, and >2 years of HAART were significantly associated with misclassification using the BED-CEIA. Some men were persistently misclassified as recently infected up to 8 years after HIV seroconversion.
C1 [Laeyendecker, Oliver] NIAID, LIR, NIH, Baltimore, MD 21205 USA.
[Laeyendecker, Oliver; Oliver, Amy E.; Mullis, Caroline E.; Eaton, Kevin P.; Mueller, Amy C.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Brookmeyer, Ron] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Jacobson, Lisa P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Brown, Joelle] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Rinaldo, Charles R.] Univ Pittsburgh, Sch Med, Dept Pathol, Med Ctr, Pittsburgh, PA USA.
[Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Laeyendecker, O (reprint author), NIAID, LIR, NIH, 855 N Wolfe St,Room 538A, Baltimore, MD 21205 USA.
EM olaeyen1@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU IV Prevention Trials Network (HPTN); National Institute of Allergy and
Infectious Diseases (NIAID), National Institute on Drug Abuse, National
Institute of Mental Health; Office of AIDS Research, of the NIH, DHHS
[U01-AI46745, U01-AI48054, U01-AI068613, UM1-AI068613]; International
Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network
[U01-AI068632]; Multicenter AIDS Cohort Study (MACS); NIAID; National
Cancer Institute; National Heart, Lung and Blood Institute [UO1-AI35042,
UL1-RR025005, UO1-AI35043, UO1-AI35039, UO1-AI35040, UO1-AI35041];
Division of Intramural Research, NIAID, NIH; [1R01-AI095068]
FX The authors thank Stacey Meyerer for her assistance with sample analysis
and the MACS study team and MACS participants for providing the samples
and data used in this study. This work was supported by (1) the HIV
Prevention Trials Network (HPTN) sponsored by the National Institute of
Allergy and Infectious Diseases (NIAID), National Institute on Drug
Abuse, National Institute of Mental Health, and Office of AIDS Research,
of the NIH, DHHS (U01-AI46745, U01-AI48054, U01-AI068613, and
UM1-AI068613), (2) 1R01-AI095068, (3) the International Maternal
Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network
(U01-AI068632), (4) the Multicenter AIDS Cohort Study (MACS) sponsored
by the NIAID, with additional supplemental funding from the National
Cancer Institute and the National Heart, Lung and Blood Institute
(UO1-AI35042, UL1-RR025005, UO1-AI35043, UO1-AI35039, UO1-AI35040, and
UO1-AI35041), and (5) the Division of Intramural Research, NIAID, NIH.
The findings and conclusions in this article are those of the authors
and do not necessarily represent the views of the National Institutes of
Health. Use of trade names is for identification purposes only and does
not constitute endorsement by the National Institutes of Health and
Prevention or the Department of Health and Human Services.
NR 29
TC 24
Z9 24
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD AUG
PY 2012
VL 28
IS 8
BP 816
EP 822
DI 10.1089/aid.2011.0258
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 977SA
UT WOS:000306683600013
PM 22014036
ER
PT J
AU Nguyen, HT
Quandt, SA
Grzywacz, JG
Chen, HY
Galvan, L
Kitner-Triolo, MH
Arcury, TA
AF Nguyen, Ha T.
Quandt, Sara A.
Grzywacz, Joseph G.
Chen, Haiying
Galvan, Leonardo
Kitner-Triolo, Melissa H.
Arcury, Thomas A.
TI Stress and cognitive function in Latino Farmworkers
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE stress; cognitive function; occupational health; farmworkers
ID MENTAL-HEALTH; LIFE-SPAN; MEMORY; BRAIN; COMMUNITY; MIGRANT; PESTICIDES;
HORMONES; FARMERS; AGE
AB Background Job stress has been associated with cognitive function, but the relationship is often overlooked when considering occupational health and safety issues of farmworkers. This study examined the relationship between stress and change in stress with change in cognitive function in a representative sample of 123 Latino farmworkers. Methods A prospective study design was used in which stress and cognitive function data were collected at baseline and at 3-month follow-up. Linear regression models were used for analyses. Potential confounders included baseline gender, age, education, number of years worked in U.S. agriculture, ever smoking status, self-rated health, and depressive symptoms. Results Baseline stress was significantly correlated with baseline cognitive function (r?=?-0.27; P?5 ng ml-1) were observed on day 1. Plasma concentrations of (2S,6S;2R,6R)-HK and (2S,6R;2R,6S)-HK were below the limit of quantification. The average (S) : (R) plasma concentrations for Ket and DHNK were <1.0 while no significant enantioselectivity was observed for norKet. There were large inter-patient variations in terminal half-lives and relative metabolite concentrations; at 230 min (R,S)-DHNK was the major metabolite in four out of nine patients, (R,S)-norKet in three out of nine patients and (2S,6S;2R,6R)-HNK in two out of nine patients. The final PK model included three compartments for (R,S)-Ket, two compartments for (R,S)-norKet and single compartments for DHNK and HNK. All PK profiles were well described, and parameters for (R,S)-Ket and (R,S)-norKet were in agreement with prior estimates.
CONCLUSION
This represents the first PK analysis of (2S,6S;2R,6R)-HNK and (R,S)-DHNK. The results demonstrate that while norKet is the initial metabolite, it is not the main metabolite suggesting that future Ket studies should include the analysis of the major metabolites.
C1 [Venkata, Swarajya Lakshmi Vattem; Moaddel, Ruin; Wainer, Irving W.] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Zhao, Xiaochen; Mager, Donald E.] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA.
[Luckenbaugh, Dave A.; Brutsche, Nancy E.; Ibrahim, Lobna; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
RP Wainer, IW (reprint author), NIA, Clin Invest Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wainerir@grc.nia.nih.gov
FU National Institute of Aging/NIH; National Institute of Mental
Health/NIH; NIH [GM57980]
FX This work was supported by the Intramural Research Program of the
National Institute of Aging/NIH (IWW) and National Institute of Mental
Health/NIH (CAZ) and NIH Grant GM57980 (DEM).
NR 29
TC 30
Z9 31
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD AUG
PY 2012
VL 74
IS 2
BP 304
EP 314
DI 10.1111/j.1365-2125.2012.04198.x
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 971QY
UT WOS:000306220100009
PM 22295895
ER
PT J
AU Sail, D
Kovac, P
AF Sail, Deepak
Kovac, Pavol
TI Benzoylated ethyl 1-thioglycosides: direct preparation from
per-O-benzoylated sugars
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE beta-Selective 1-O-benzoylation; Thioglycosylation; Thioglycosidation
ID METHYL BETA-GLYCOSIDES; OLIGOSACCHARIDE SYNTHESIS; DONORS;
THIOGLYCOSIDES; TRIFLUOROMETHANESULFONATE; SULFONATE; CERAMIDE
AB D-Glucose, lactose, maltose, and melibiose were benzoylated with Bz(2)O-Et3N reagent to give fully benzoylated beta products. Under the same conditions, D-mannose produced a mixture where the beta-benzoate predominated. Treatment of the foregoing compounds with EtSH at slightly elevated temperature (50-60 degrees C) in the presence of BF3 center dot Et2O as a promoter gave the corresponding ethyl 1-thio glycosides in high yields. The a-products predominated in all cases in the anomeric mixtures formed. Individual products of all reactions were isolated by chromatography, they were obtained in analytically pure state, and were fully characterized by H-1 and C-13 NMR data and physical constants. Published by Elsevier Ltd.
C1 [Sail, Deepak; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
EM kpn@helix.nih.gov
RI Kovac, Pavol/B-8813-2008
OI Kovac, Pavol/0000-0001-5044-3449
FU NIH, NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK.
NR 34
TC 5
Z9 5
U1 1
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD AUG 1
PY 2012
VL 357
BP 47
EP 52
DI 10.1016/j.carres.2012.05.012
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 972JP
UT WOS:000306273700006
PM 22739243
ER
PT J
AU Tonry, JH
McNichol, BA
Ramarao, N
Chertow, DS
Kim, KS
Stibitz, S
Schneewind, O
Kashanchi, F
Bailey, CL
Popov, S
Chung, MC
AF Tonry, Jessica H.
McNichol, Beth A.
Ramarao, Nalini
Chertow, Daniel S.
Kim, Kwang Sik
Stibitz, Scott
Schneewind, Olaf
Kashanchi, Fatah
Bailey, Charles L.
Popov, Serguei
Chung, Myung-Chul
TI Bacillus anthracis protease InhA regulates BslA-mediated adhesion in
human endothelial cells
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID MURINE MACROPHAGES; S-LAYER; SPORES; CAPSULE; GENE; THURINGIENSIS;
VIRULENCE; PLASMID; CEREUS; ESCAPE
AB To achieve widespread dissemination in the host, Bacillus anthracis cells regulate their attachment to host endothelium during infection. Previous studies identified BslA (Bacillus anthracisS-layer Protein A), a virulence factor of B. anthracis, as necessary and sufficient for adhesion of vegetative cells to human endothelial cells. While some factors have been identified, bacteria-specific contributions to BslA mediated adhesion remain unclear. Using the attenuated vaccine Sterne 7702 strain of B. anthracis, we tested the hypothesis that InhA (immune inhibitor A), a B. anthracis protease, regulates BslA levels affecting the bacteria's ability to bind to endothelium. To test this, a combination of inhA mutant and complementation analysis in adhesion and invasion assays, Western blot and InhA inhibitor assays were employed. Results show InhA downregulates BslA activity reducing B. anthracis adhesion and invasion in human brain endothelial cells. BslA protein levels in ?inhA bacteria were significantly higher than wild-type and complemented strains showing InhA levels and BslA expression are inversely related. BslA was sensitive to purified InhA degradation in a concentration- and time-dependent manner. Taken together these data support the role of InhA regulation of BslA-mediated vegetative cell adhesion and invasion.
C1 [Tonry, Jessica H.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei; Chung, Myung-Chul] George Mason Univ, Dept Biosci, Manassas, VA 20110 USA.
[Tonry, Jessica H.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei; Chung, Myung-Chul] George Mason Univ, Biomed Res Lab, Manassas, VA 20110 USA.
[McNichol, Beth A.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Ramarao, Nalini] INRA Micalis UMR Microbienne & Environm 1319, F-78285 La Miniere, Guyancourt, France.
[Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kim, Kwang Sik] Johns Hopkins Univ, Div Pediat Infect Dis, Sch Med, Baltimore, MD 21287 USA.
[Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
RP Chung, MC (reprint author), George Mason Univ, Dept Biosci, 10650 Pyramid Pl, Manassas, VA 20110 USA.
EM mchung3@gmu.edu
FU U.S. Department of Energy [DE-FC52-FC04NA25455]
FX We thank members of our laboratory for critical comments and discussion.
We thank David Derby, a George Mason University aspiring scientist
summer internship student (ASSIP) for skilled technical assistance. This
work was supported by the U.S. Department of Energy Grant
DE-FC52-FC04NA25455.
NR 30
TC 9
Z9 10
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD AUG
PY 2012
VL 14
IS 8
BP 1219
EP 1230
DI 10.1111/j.1462-5822.2012.01791.x
PG 12
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 974BO
UT WOS:000306405000007
PM 22452315
ER
PT J
AU Lim, H
Kane, L
Schwartz, JB
Hesdorffer, CS
Deeks, SG
Greig, N
Ferrucci, L
Goetzl, EJ
AF Lim, H.
Kane, L.
Schwartz, J. B.
Hesdorffer, C. S.
Deeks, S. G.
Greig, N.
Ferrucci, L.
Goetzl, E. J.
TI Lenalidomide enhancement of human T cell functions in human
immunodeficiency virus (HIV)-infected and HIV-negative CD4 T
lymphocytopenic patients
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE AIDS; chemotaxis; cytokines; immunopharmacology; T lymphocytes
ID AGE-RELATED COMORBIDITIES; FUNCTION IN-VITRO; HOMOSEXUAL MEN; INFECTION;
MORTALITY; INFLAMMATION; ATHEROSCLEROSIS; PROGRESSION; POPULATION;
CHEMOKINE
AB Suppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n = 6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n = 6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000 nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-?, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 101000 nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle-aged men and reconstituted in vitro at a low CD4 : CD8 ratio typical of HIV infection had depressed chemotaxis to S1P, but not CCL21, and generation of IL-2, but not IFN-?. Significant enhancement of chemotaxis to S1P and CCL21was induced by 1001000 nM lenalidomide only for normal T cells at a low CD4 : CD8 ratio. T cells from HIV-negative middle-aged CD4 T lymphocytopenic patients (n = 3), with a CD4 : CD8 ratio as low as that of HIV-infected patients, had similarly diminished chemotaxis to S1P and CCL21, and depressed generation of IL-2, but not IFN-?. Lenalidomide at 301000 nM significantly enhanced chemotaxis to S1P and IL-2 generation for T cells from HIV-negative CD4 T lymphocytopenic patients as from HIV-infected patients, with less effect on CCL21-elicited chemotaxis and none for IFN-? generation. Defects in functions of T cells from middle-aged HIV-infected men are partially attributable to CD4 T lymphocytopenia and are corrected by lenalidomide.
C1 [Lim, H.; Kane, L.; Schwartz, J. B.; Deeks, S. G.; Goetzl, E. J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Lim, H.; Kane, L.; Schwartz, J. B.; Deeks, S. G.; Goetzl, E. J.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA.
[Kane, L.; Schwartz, J. B.; Goetzl, E. J.] Univ Calif San Francisco, Jewish Home San Francisco, Geriatr Res Ctr, San Francisco, CA 94143 USA.
[Schwartz, J. B.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Hesdorffer, C. S.; Greig, N.; Ferrucci, L.; Goetzl, E. J.] NIA, Baltimore, MD 21224 USA.
RP Goetzl, EJ (reprint author), UCSF JHSF, Geriatr Res Ctr, 302 Silver Ave, San Francisco, CA 94112 USA.
EM edward.goetzl@ucsf.edu
FU Jewish Home of San Francisco; National Institute on Aging
FX This research was supported by endowment funds of the Jewish Home of San
Francisco and the intramural research programme of the National
Institute on Aging. The authors are grateful to Judith H. Goetzl for
preparation of the figures and tables and for editorial suggestions.
NR 32
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD AUG
PY 2012
VL 169
IS 2
BP 182
EP 189
DI 10.1111/j.1365-2249.2012.04603.x
PG 8
WC Immunology
SC Immunology
GA 970JL
UT WOS:000306124100013
PM 22774993
ER
PT J
AU Rothenbuhler, A
Horvath, A
Libe, R
Faucz, FR
Fratticci, A
Sanson, MLR
Vezzosi, D
Azevedo, M
Levy, I
Almeida, MQ
Lodish, M
Nesterova, M
Bertherat, J
Stratakis, CA
AF Rothenbuhler, Anya
Horvath, Anelia
Libe, Rossella
Faucz, Fabio R.
Fratticci, Amato
Sanson, Marie L. Raffin
Vezzosi, Delphine
Azevedo, Monalisa
Levy, Isaak
Almeida, Madson Q.
Lodish, Maya
Nesterova, Maria
Bertherat, Jerome
Stratakis, Constantine A.
TI Identification of novel genetic variants in phosphodiesterase 8B ( PDE8B
), a cAMP-specific phosphodiesterase highly expressed in the adrenal
cortex, in a cohort of patients with adrenal tumours
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID REGULATORY SUBUNIT; CARNEY COMPLEX; MUTATIONS; HYPERPLASIA; PDE11A; 11A;
ADENOMAS
AB Background Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions. Objective To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours. Design and subjects This is a casecontrol study followed by functional analyses. Two hundred and sixteen unrelated patients with different types of adrenocortical tumours and 192 healthy control individuals participated in the study. Methods Bidirectional Sanger sequencing, in vitro cell line transfection and in silico modelling are used in this study. Results Nine different PDE8B sequence changes, six novel and three previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico. Conclusion PDE8B is another PDE gene in which variations may contribute to predisposition of adrenocortical tumours.
C1 [Rothenbuhler, Anya; Horvath, Anelia; Faucz, Fabio R.; Azevedo, Monalisa; Almeida, Madson Q.; Lodish, Maya; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Rothenbuhler, Anya; Horvath, Anelia; Faucz, Fabio R.; Azevedo, Monalisa; Levy, Isaak; Almeida, Madson Q.; Lodish, Maya; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Genet & Pediat Endocrinol Training Program, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Libe, Rossella; Fratticci, Amato; Sanson, Marie L. Raffin; Vezzosi, Delphine; Bertherat, Jerome] CNRS, INSERM, U1016, Metab & Canc Inst,Dept Endocrinol,UMR 8104, F-75700 Paris, France.
[Libe, Rossella; Fratticci, Amato; Sanson, Marie L. Raffin; Vezzosi, Delphine; Bertherat, Jerome] Univ Paris Descartes Paris, Paris, France.
[Libe, Rossella; Bertherat, Jerome] Hop Cochin, AP HP, Dept Endocrinol, Ctr Rare Adrenal Dis, Paris, France.
[Libe, Rossella; Bertherat, Jerome] INCa Comete Network Adrenal Canc, Paris, France.
[Sanson, Marie L. Raffin] Hop Ambroise Pare, AP HP, Boulogne, France.
RP Stratakis, CA (reprint author), NICHD, Endocrinol Sect, PDEGEN, NIH,CRC, Bldg 10,Room I-1330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Agence Nationale pour la Recherche [ANR06-MRAR-007, ANR08-GENOPAT-002];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development intramural National Institutes of Health [Z01-HD-000642-04]
FX This work was supported by grants from the Agence Nationale pour la
Recherche (ANR06-MRAR-007 and ANR08-GENOPAT-002) and supported, in part,
by the Eunice Kennedy Shriver National Institute of Child Health and
Human Development intramural National Institutes of Health Project
Z01-HD-000642-04 (to C.A.S.)
NR 16
TC 29
Z9 29
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD AUG
PY 2012
VL 77
IS 2
BP 195
EP 199
DI 10.1111/j.1365-2265.2012.04366.x
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 971SF
UT WOS:000306223400005
PM 22335482
ER
PT J
AU Bekker, LG
Beyrer, C
Quinn, TC
AF Bekker, Linda-Gail
Beyrer, Chris
Quinn, Thomas C.
TI Behavioral and Biomedical Combination Strategies for HIV Prevention
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; SUB-SAHARAN AFRICA; ACTIVE
ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED
CONTROLLED-TRIAL; FEMALE SEX WORKERS; HOMOSEXUAL BISEXUAL MEN;
HERPES-SIMPLEX-VIRUS; MALE CIRCUMCISION; HETEROSEXUAL TRANSMISSION
AB Around 2.5 million people become infected with HIV each year. This extraordinary toll on human life and public health worldwide will only be reversed with effective prevention. What's more, in the next few years, it is likely at least, that no single prevention strategy will be sufficient to contain the spread of the disease. There is a need for combination prevention as there is for combination treatment, including biomedical, behavioral, and structural interventions. Expanded HIV prevention must be grounded in a systematic analysis of the epidemic's dynamics in local contexts. Although 85% of HIV is transmitted sexually, effective combinations of prevention have been shown for people who inject drugs. Combination prevention should be based on scientifically derived evidence, with input and engagement from local communities that fosters the successful integration of care and treatment.
C1 [Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Beyrer, Chris] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Sect Int HIV STD Res, NIH, Bethesda, MD 20892 USA.
RP Bekker, LG (reprint author), Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
EM Linda-gail.bekker@hiv-research.org.za
NR 146
TC 0
Z9 0
U1 1
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD AUG
PY 2012
VL 4
IS 8
AR a007435
DI 10.1101/cshperspect.a007435
PG 23
WC Cell Biology
SC Cell Biology
GA 995RR
UT WOS:000308030500004
ER
PT J
AU Bekker, LG
Beyrer, C
Quinn, TC
AF Bekker, Linda-Gail
Beyrer, Chris
Quinn, Thomas C.
TI Behavioral and Biomedical Combination Strategies for HIV Prevention
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; SUB-SAHARAN AFRICA; ACTIVE
ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED
CONTROLLED-TRIAL; FEMALE SEX WORKERS; HOMOSEXUAL BISEXUAL MEN;
HERPES-SIMPLEX-VIRUS; MALE CIRCUMCISION; HETEROSEXUAL TRANSMISSION
AB Around 2.5 million people become infected with HIV each year. This extraordinary toll on human life and public health worldwide will only be reversed with effective prevention. What's more, in the next few years, it is likely at least, that no single prevention strategy will be sufficient to contain the spread of the disease. There is a need for combination prevention as there is for combination treatment, including biomedical, behavioral, and structural interventions. Expanded HIV prevention must be grounded in a systematic analysis of the epidemic's dynamics in local contexts. Although 85% of HIV is transmitted sexually, effective combinations of prevention have been shown for people who inject drugs. Combination prevention should be based on scientifically derived evidence, with input and engagement from local communities that fosters the successful integration of care and treatment.
C1 [Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Beyrer, Chris] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Sect Int HIV STD Res, NIH, Bethesda, MD 20892 USA.
RP Bekker, LG (reprint author), Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
EM Linda-gail.bekker@hiv-research.org.za
NR 146
TC 7
Z9 8
U1 2
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD AUG
PY 2012
VL 2
IS 8
AR a007435
DI 10.1101/cshperspect.a007435
PG 23
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 080YH
UT WOS:000314279800005
ER
PT J
AU Barrett, L
Walmsley, S
AF Barrett, Lisa
Walmsley, Sharon
TI CMV Retinopathy in the Antiretroviral Therapy Era: Prevention,
Diagnosis, and Management
SO CURRENT INFECTIOUS DISEASE REPORTS
LA English
DT Article
DE HIV; CMV; Retinitis; Antiretroviral therapy; Management; Diagnosis
AB Before the advent of antiretroviral therapy (ART), CMV retinitis was a common, debilitating opportunistic infection in the HIV-infected population. ART has had such a favorable impact on the prevention and management of CMV retinitis that it can be considered in some ways to be CMV therapy. Currently available CMV directed antiviral therapies are quite successful at limiting vision loss, but in resource limited settings there is still significant morbidity associated with the disease. This review summarizes the pathology, diagnosis, clinical course and treatment of retinitis in the pre-ART era to provide context for the contemporary clinical scenario, and highlights current management strategies. Important questions concerning host correlates of susceptibility and ideal therapy in the context of drug resistance are also briefly reviewed.
C1 [Barrett, Lisa] NIH, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Walmsley, Sharon] Univ Toronto, Div Infect Dis, Univ Hlth Network, Toronto, ON, Canada.
RP Walmsley, S (reprint author), Univ Toronto, Div Infect Dis, Univ Hlth Network, 13EN Rm 214,200 Elizabeth St, Toronto, ON, Canada.
EM Sharon.Walmsley@uhn.ca
NR 68
TC 6
Z9 6
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3847
EI 1534-3146
J9 CURR INFECT DIS REP
JI Curr. Infect. Dis. Rep.
PD AUG
PY 2012
VL 14
IS 4
BP 435
EP 444
DI 10.1007/s11908-012-0269-1
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA V32XF
UT WOS:000208983200011
PM 22688820
ER
PT J
AU Mejia, R
Nutman, TB
AF Mejia, Rojelio
Nutman, Thomas B.
TI Screening, prevention, and treatment for hyperinfection syndrome and
disseminated infections caused by Strongyloides stercoralis
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE anthelmintic therapy; immunocompromised; infection; screening;
Strongyloides
ID INTESTINAL PARASITES; IVERMECTIN; TRANSPLANTATION; EOSINOPHILIA;
PREVALENCE; DIAGNOSIS; PATIENT; VIRUS; THERAPY; DISEASE
AB Purpose of review
This review discusses the latest approaches to the diagnosis and treatment of patients with strongyloidiasis, with an emphasis on infection in the immunocompromised host and the risk for disseminated strongyloidiasis.
Recent findings
The differences in acute, chronic, accelerated autoinfection, and disseminated disease in Strongyloides stercoralis infection are explored with particular emphasis on early diagnosis, treatment, and prevention. The goals of treatment are investigated for the different infection states. Predisposing risks for dissemination are delineated, and the roles played for newer diagnostics in the identification of at-risk individuals are detailed.
Summary
The use of newer diagnostic tests and broader screening of immunocompromised patients from Strongyloides-endemic areas is of paramount importance, particularly if prevention of life-threatening dissemination is the goal.
C1 [Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Nutman, TB (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Funding was received from the National Institutes of Health. This work
was supported by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 52
TC 67
Z9 70
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7375
EI 1473-6527
J9 CURR OPIN INFECT DIS
JI Curr. Opin. Infect. Dis.
PD AUG
PY 2012
VL 25
IS 4
BP 458
EP 463
DI 10.1097/QCO.0b013e3283551dbd
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 970LS
UT WOS:000306131100013
PM 22691685
ER
PT J
AU Masdeu, JC
AF Masdeu, Joseph C.
TI Imaging brain networks and brain diseases
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Editorial Material
ID MRI
C1 NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bldg 10,Room 3C111,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM masdeu@nih.gov
FU Intramural NIH HHS
NR 5
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2012
VL 25
IS 4
BP 373
EP 374
DI 10.1097/WCO.0b013e328355a300
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 970KB
UT WOS:000306125900001
PM 22710360
ER
PT J
AU Masdeu, JC
Kreisl, WC
Berman, KF
AF Masdeu, Joseph C.
Kreisl, William C.
Berman, Karen F.
TI The neurobiology of Alzheimer disease defined by neuroimaging
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Review
DE Alzheimer disease; amyloid beta; magnetic resonance imaging; mild
cognitive impairment; positron emission tomography
ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; BETA-AMYLOID
DEPOSITION; COMPOUND-B; FUNCTIONAL CONNECTIVITY; LEWY BODIES;
ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE;
CORTICAL THICKNESS
AB Purpose of review
In 2011, a new set of new guidelines for the research diagnosis of three stages of Alzheimer disease was promulgated by the US National Institute of Aging and the Alzheimer Association. For the first time, they include the diagnosis of presymptomatic Alzheimer disease, recognizing that the disease process begins years before cognitive impairment develops. Awareness of this fact has largely been driven by neuroimaging, and particularly by imaging amyloid beta (abeta) deposition in the brain, a procedure approved by the US Food and Drug Administration for clinical use in April 2012.
Recent findings
In Alzheimer disease, abeta deposition antecedes, probably by decades, the onset of cognitive impairment. In brain regions with greatest abeta deposition, synaptic dysfunction can be imaged beginning at preclinical stages. In regions that are not identical with the ones with greatest abeta deposition but heavily connected with them, regional atrophy and loss of white-matter anisotropy can be detected later in the course of the disease, near the time when mild cognitive impairment supervenes. Together with neuropsychological testing, imaging can improve the prediction of worsening to Alzheimer disease among patients with mild cognitive impairment.
Summary
These findings have huge implications for research on therapeutic approaches to Alzheimer disease. For instance, while so far only patients with the clinical diagnosis have been treated with immunotherapy targeting abeta removal, a consensus is building that to be effective, this therapy should be given in the preclinical stages of the disease, which are assessed most advantageously by means of neuroimaging.
C1 [Masdeu, Joseph C.; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Kreisl, William C.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bldg 10,Room 3C111,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM masdeu@nih.gov
FU National Institutes of Health; American Academy of Neurology Foundation;
Biomarker's Consortium
FX This work was supported by the Intramural Research Program of the
National Institutes of Health.; Dr Masdeu receives an honorarium as
editor-in-chief of the Journal of Neuroimaging. Dr Kreisl received
funding from the American Academy of Neurology Foundation through a
clinical research training fellowship grant, and from the Biomarker's
Consortium, a partnership of the Foundation for NIH and industry. Dr
Berman does not report any conflict of interest.
NR 133
TC 20
Z9 20
U1 3
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2012
VL 25
IS 4
BP 410
EP 420
DI 10.1097/WCO.0b013e3283557b36
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 970KB
UT WOS:000306125900006
PM 22766722
ER
PT J
AU Czarnecki, K
Hallett, M
AF Czarnecki, Kathrin
Hallett, Mark
TI Functional (psychogenic) movement disorders
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Review
DE conversion; hysteria; neurophysiology; psychogenic movement disorders
ID COGNITIVE-BEHAVIORAL THERAPY; MOTOR CONVERSION DISORDER; PERIPHERAL
TRAUMA; FIXED DYSTONIA; TEMPORAL DISCRIMINATION; NONEPILEPTIC SEIZURES;
MENTAL ROTATION; BODY PARTS; TREMOR; PLASTICITY
AB Purpose of review
This review provides an overview of recent developments in diagnosis, pathophysiology, neuroimaging and management of functional (psychogenic) movement disorders (FMD).
Recent findings
There has been increasing interest to study the underlying pathophysiology of FMD, which has resulted in a broadened disease model, taking neurobiologic and psychosocial factors equally into account. In this context, the term 'psychogenic' has been replaced by 'functional' movement disorders by many authors in the field to express the changing focus toward a multifactorial disease model. The need for establishing a positive diagnosis of FMD as opposed to providing a diagnosis of exclusion is increasingly recognized and reflected by the introduction of 'laboratory-supported' diagnostic criteria of FMD. Important advances have been made through behavioral, electrophysiological and neuroimaging studies, although the fundamental cause of FMD remains poorly understood. Of particular interest have been several reports on abnormal sensorimotor features and cortical inhibition in both organic and functional dystonia, highlighting possible shared traits of both conditions. In terms of treatment, recent studies have reported benefit from both psychiatric and physical therapy-based interventions.
Summary
Increasing efforts have been made toward better understanding of FMD, and the disease model has been broadened to include neurobiologic and psychosocial factors. Laboratory-based diagnostic criteria have been established for many FMD to support the clinical diagnosis. To determine the most effective management strategies for FMD, a closer collaboration between neurologists and psychiatrists and intensified research efforts with prospective treatment trials are needed.
C1 [Czarnecki, Kathrin; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS002667-23]
NR 58
TC 11
Z9 11
U1 3
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2012
VL 25
IS 4
BP 507
EP 512
DI 10.1097/WCO.0b013e3283551bc1
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 970KB
UT WOS:000306125900017
PM 22610460
ER
PT J
AU Sung, HY
Kim, SW
Kang, WK
Kim, SY
Jung, CK
Cho, YK
Park, JM
Lee, IS
Choi, MG
Chung, IS
AF Sung, Hye Young
Kim, Sang Woo
Kang, Won Kyung
Kim, Su Young
Jung, Chan-Kwon
Cho, Yu Kyung
Park, Jae Myung
Lee, In Seok
Choi, Myung-Gyu
Chung, In-Sik
TI Long-term prognosis of an endoscopically treated rectal neuroendocrine
tumor: 10-year experience in a single institution
SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Article
DE colorectal neuroendocrine tumor; endoscopic resection; long-term
prognosis
ID EARLY GASTRIC-CANCER; CARCINOID-TUMORS; SUBMUCOSAL DISSECTION; MUCOSAL
RESECTION; LIGATION DEVICE; EMR
AB Background and aim The endoscopic techniques for treating a small rectal neuroendocrine tumor (NET) are performed in most large centers; however, the endoscopic management of this condition is not well established. This study was designed to determine the long-term prognosis of endoscopically resected NET.
Methods We prospectively studied patients with endoscopically treated rectal NET in Seoul St Mary's hospital, between January 2000 and June 2010. The long-term outcomes were analyzed in association with the pathological complete resection and resection procedures.
Results Seventy-seven patients (48 men and 29 women; mean age, 52.3 years; range, 23-77 years) were included. The average NET size was 7.0 +/- 2.8mm (range, 3-16 mm). There was no procedure-related complication. En-bloc removal was achieved for all lesions, and the rate of histological complete resection was 75.3% (58/77). Histological complete resection rates were 71.4% (10/14) by conventional endoscopic mucosal resection (EMR), 74.1% (43/58) by a two-channel EMR, and 100.0% (5/5) by endoscopic submucosal dissection (ESD). Among six patients with incomplete histological resection, two underwent additional EMR, two underwent transanal endoscopic microsurgery, and two underwent low anterior section with lymph node dissection. The remaining 13 patients with 'possible' remnant NET underwent regular endoscopic surveillance without additional resection. In the latter group, only one patient had local recurrence, detected on regular colonoscopic surveillance, after 56 months and was treated with additional EMR. All of the patients are alive and 98.7% (76/77) of the patients are free from disease during the follow-up periods.
Conclusion Endoscopic resection is a safe and effective modality and may potentially be used for the treatment of NETs smaller than 15mm in diameter, those confined to the submucosal layer, and those without metastasis. Local treatment was believed to be curative in cases with complete histological resection. In addition, this treatment may have an excellent prognosis in patients with 'possible' remnant NET. Eur J Gastroenterol Hepatol 24:978-983 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Kang, Won Kyung] Catholic Univ, Dept Surg, Coll Med, Seoul, South Korea.
[Kim, Su Young] Catholic Univ, Dept Pathol, Coll Med, Seoul, South Korea.
[Jung, Chan-Kwon] Catholic Univ, Dept Hosp Pathol, Coll Med, Seoul, South Korea.
[Sung, Hye Young] NCI, Mol Pharmacol Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Sung, Hye Young; Kim, Sang Woo; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Choi, Myung-Gyu; Chung, In-Sik] Catholic Univ, Dept Internal Med, Div Gastroenterol, Coll Med, Seoul, South Korea.
RP Kim, SW (reprint author), Seoul St Marys Hosp, Dept Internal Med, Div Gastroenterol, 505 Banpo Dong, Seoul 137701, South Korea.
EM viper@catholic.ac.kr
RI Choi, Myung-Gyu/D-6079-2014;
OI Choi, Myung-Gyu/0000-0003-4083-5187; Lee, In Seok/0000-0002-1127-1522
FU Catholic Medical Center Research Foundation
FX This work was supported by the Catholic Medical Center Research
Foundation; founded in 2008.
NR 30
TC 16
Z9 17
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0954-691X
J9 EUR J GASTROEN HEPAT
JI Eur. J. Gastroenterol. Hepatol.
PD AUG
PY 2012
VL 24
IS 8
BP 978
EP 983
DI 10.1097/MEG.0b013e3283551e0b
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 972PM
UT WOS:000306289300017
PM 22647741
ER
PT J
AU Thorgeirsson, SS
AF Thorgeirsson, S. S.
TI The central role of the c-Met pathway in rebuilding the liver
SO GUT
LA English
DT Editorial Material
ID HEPATOCYTE GROWTH-FACTOR; TRANSPLANTATION
C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
NR 10
TC 3
Z9 3
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD AUG
PY 2012
VL 61
IS 8
BP 1105
EP 1106
DI 10.1136/gutjnl-2012-302234
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 971CJ
UT WOS:000306180700001
PM 22387525
ER
PT J
AU Cruz, RA
Wilkinson, AV
Bondy, ML
Koehly, LM
AF Cruz, Rick A.
Wilkinson, Anna V.
Bondy, Melissa L.
Koehly, Laura M.
TI Psychometric Evaluation of the Demographic Index of Cultural Exposure
(DICE) in Two Mexican-Origin Community Samples
SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES
LA English
DT Article
DE Mexican American; acculturation; index; immigrant; health
ID ACCULTURATION SCALE; MENTAL-HEALTH; US HISPANICS; FIT INDEXES;
ADOLESCENTS; AMERICANS; ADULTS; BEHAVIORS; NATIVITY; VALUES
AB Reliability and validity evidence is provided for the Demographic Index of Cultural Exposure (DICE), consisting of six demographic proxy indicators of acculturation, within two community samples of Mexican-origin adults (N= 497 for each sample). Factor analytic procedures were used to examine the common variance shared between the six demographic indicators hypothesized to correlate with acculturation. The index was cross-validated across two samples by comparing fit indices. Finally, index criterion validity was assessed using correlations between index scores and five common behavioral/psychological domains of Latino cultural identity: language use (Spanish and English), cultural practices, folk health beliefs, and fatalism. Results indicated that the six demographic indicators loaded onto one latent factor and that this model had good fit across both samples. In addition, DICE scores correlated with four of the five behavioral/psychological measures. Future use of the DICE as an efficient way to approximate cultural exposure is discussed.
C1 [Koehly, Laura M.] NHGRI, Bethesda, MD 20892 USA.
[Cruz, Rick A.] Univ Washington, Seattle, WA 98195 USA.
[Wilkinson, Anna V.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA.
[Bondy, Melissa L.] Baylor Coll Med, Houston, TX 77030 USA.
RP Koehly, LM (reprint author), NHGRI, 31Center Dr,Bldg 31,Room B1B37D, Bethesda, MD 20892 USA.
EM koehlyl@mail.nih.gov
NR 42
TC 2
Z9 2
U1 3
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0739-9863
J9 HISPANIC J BEHAV SCI
JI Hisp. J. Behav. Sci.
PD AUG
PY 2012
VL 34
IS 3
BP 404
EP 420
DI 10.1177/0739986312449426
PG 17
WC Psychology, Multidisciplinary
SC Psychology
GA 971BJ
UT WOS:000306176500002
ER
PT J
AU de Groot, NG
Otting, N
Robinson, J
Blancher, A
Lafont, BAP
Marsh, SGE
O'Connor, DH
Shiina, T
Walter, L
Watkins, DI
Bontrop, RE
AF de Groot, Natasja G.
Otting, Nel
Robinson, James
Blancher, Antoine
Lafont, Bernard A. P.
Marsh, Steven G. E.
O'Connor, David H.
Shiina, Takashi
Walter, Lutz
Watkins, David I.
Bontrop, Ronald E.
TI Nomenclature report on the major histocompatibility complex genes and
alleles of Great Ape, Old and New World monkey species
SO IMMUNOGENETICS
LA English
DT Article
DE MHC; NHP; Database; Nomenclature; IPD
ID MHC CLASS-I; INFECTED RHESUS-MONKEYS; CYNOMOLGUS MACAQUES;
SAGUINUS-OEDIPUS; HLA SYSTEM; T-CELLS; G LOCUS; PRIMATE; DIVERSITY;
EVOLUTION
AB The major histocompatibility complex (MHC) plays a central role in the adaptive immune response. The MHC region is characterised by a high gene density, and most of these genes display considerable polymorphism. Next to humans, non-human primates (NHP) are well studied for their MHC. The present nomenclature report provides the scientific community with the latest nomenclature guidelines/rules and current implemented nomenclature revisions for Great Ape, Old and New World monkey species. All the currently published MHC data for the different Great Ape, Old and New World monkey species are archived at the Immuno Polymorphism Database (IPD)-MHC NHP database. The curators of the IPD-MHC NHP database are, in addition, responsible for providing official designations for newly detected polymorphisms.
C1 [de Groot, Natasja G.; Otting, Nel; Bontrop, Ronald E.] Biomed Primate Res Ctr, Dept Comparat Genet & Refinement, NL-2288 GJ Rijswijk, Netherlands.
[Robinson, James; Marsh, Steven G. E.] Royal Free Hosp, Anthony Nolan Res Inst, London NW3 2QG, England.
[Blancher, Antoine] Univ Toulouse 3, Mol Immunoregulat Lab, Fac Med Purpan, F-31062 Toulouse 3, France.
[Lafont, Bernard A. P.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Marsh, Steven G. E.] UCL, UCL Canc Inst, London NW3 2QG, England.
[O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53711 USA.
[Shiina, Takashi] Tokai Univ, Sch Med, Dept Mol Life Sci, Div Basic Med Sci & Mol Med, Kanagawa 2591100, Japan.
[Walter, Lutz] Leibniz Inst Primate Res, Primate Genet Lab, German Primate Ctr, D-37077 Gottingen, Germany.
[Watkins, David I.] Univ Miami, Sch Med, Dept Pathol, Miami, FL 33136 USA.
[Bontrop, Ronald E.] Univ Utrecht, NL-3584 CH Utrecht, Netherlands.
RP de Groot, NG (reprint author), Biomed Primate Res Ctr, Dept Comparat Genet & Refinement, Lange Kleiweg 161, NL-2288 GJ Rijswijk, Netherlands.
EM groot@bprc.nl
RI Robinson, James/A-2056-2011; Bontrop, Ronald/J-3628-2012; Lafont,
Bernard/B-7236-2014;
OI Robinson, James/0000-0002-2187-5944; Bontrop,
Ronald/0000-0003-0874-6467; o'connor, david/0000-0003-2139-470X; Walter,
Lutz/0000-0001-9408-3131
FU NIH/NIAID [HHSN266200400088C, 5R24RR016038-05, HHSN272201100013C];
intramural research program of NIAID-NIH
FX The authors would like to thank D. Devine for editing the manuscript and
H. van Westbroek for preparing the figures. This study was supported in
part by NIH/NIAID contract numbers HHSN266200400088C, 5R24RR016038-05,
and HHSN272201100013C. Bernard A.P. Lafont is supported by the
intramural research program of NIAID-NIH.
NR 63
TC 41
Z9 42
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
J9 IMMUNOGENETICS
JI Immunogenetics
PD AUG
PY 2012
VL 64
IS 8
BP 615
EP 631
DI 10.1007/s00251-012-0617-1
PG 17
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 973EX
UT WOS:000306341300005
PM 22526602
ER
PT J
AU Stang, A
Trabert, B
Wentzensen, N
Cook, MB
Rusner, C
Oosterhuis, JW
McGlynn, KA
AF Stang, A.
Trabert, B.
Wentzensen, N.
Cook, M. B.
Rusner, C.
Oosterhuis, J. W.
McGlynn, K. A.
TI Gonadal and extragonadal germ cell tumours in the United States,
1973-2007
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE extragonadal germ cell tumours; germ cell tumours; incidence; ovarian
neoplasms; testicular neoplasms; time trends
ID GENETIC-ANALYSIS; DIAGNOSIS; TERATOMAS; MIDLINE; TESTIS; 12P
AB Germ cell tumours (GCTs) most often arise in the gonads, but some develop extragonadally. The aim of this study was to examine gender- and race-specific trends in incidence and survival of gonadal (GGCTs) and extragonadal GCTs (EGCTs) in the US from 1973 to 2007. We also examined the topographical distribution of EGCTs by race and gender. We estimated age-specific and age-standardized incidence rates and 5-year relative survival rates (RSR) of GCTs using the Surveillance, Epidemiology and End Results (SEER) Program (SEER nine registries). GCTs and their topographical sites were identified using ICD-O morphology and topography codes. Of 21 170 GCTs among males, 5.7% were extragonadal (Whites 5.5%; Blacks 16.3%). Of 2093 GCTs among females, 39.3% were extragonadal (Whites, 36.9%; Blacks 51.0%). The incidence of GGCT was much higher among White (56.3/1 000 000) than Black males (10.0/1 000 000), while there was no difference in incidence between White and Black females (3.2/1 000 000). The rates of EGCT among men and women of both races were similar (range:1.93.4/1 000 000). The most frequent extragonadal sites were mediastinum among males and placenta among females. The 5-year RSR of testicular GCT was higher among Whites (97%) than Blacks (90%), as was the 5-year RSR of ovarian GCT (Whites, 92%; Blacks 85%). In general, the 5-year RSRs of EGCTs were lower than the 5-year RSRs of GGCTs. The different incidence trends of GGCTs and EGCTs and distinct age-specific incidence patterns by anatomical site of EGCTs suggest that GGCTs and EGCTs may have different aetiologies.
C1 [Stang, A.; Rusner, C.] Univ Halle Wittenberg, Inst Clin Epidemiol, Fac Med, D-06097 Halle, Saale, Germany.
[Trabert, B.; Wentzensen, N.; Cook, M. B.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Oosterhuis, J. W.] Erasmus MC, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands.
RP Stang, A (reprint author), Univ Halle Wittenberg, Inst Clin Epidemiol, Fac Med, Magdeburger Str 8, D-06097 Halle, Saale, Germany.
EM andreas.stang@medizin.uni-halle.de
RI Cook, Michael/A-5641-2009; Trabert, Britton/F-8051-2015
OI Cook, Michael/0000-0002-0533-7302;
FU Deutsche Forschungsgemeinschaft (DFG) [STA 621/6-1, RU 1659/1-1]; NCI
Intramural Research Program, NIH, DHHS
FX Dr Stang was a recipient of a grant from the Deutsche
Forschungsgemeinschaft (DFG), grant number STA 621/6-1. Dr Rusner was a
recipient of a grant from the Deutsche Forschungsgemeinschaft (DFG),
grant number RU 1659/1-1. Drs Trabert, Cook, Wentzensen and McGlynn are
supported by the NCI Intramural Research Program, NIH, DHHS. All authors
had substantial contributions to research design, data analysis,
interpretation of data, drafting and revising the paper.
NR 28
TC 25
Z9 26
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-6263
J9 INT J ANDROL
JI Int. J. Androl.
PD AUG
PY 2012
VL 35
IS 4
BP 616
EP 625
DI 10.1111/j.1365-2605.2011.01245.x
PG 10
WC Andrology
SC Endocrinology & Metabolism
GA 972VL
UT WOS:000306309100016
PM 22320869
ER
PT J
AU Schnall, R
Cimino, JJ
Bakken, S
AF Schnall, Rebecca
Cimino, James J.
Bakken, Suzanne
TI Development of a prototype continuity of care record with
context-specific links to meet the information needs of case managers
for persons living with HIV
SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
LA English
DT Article
DE Information needs; Context-specific links; Continuity of Care Record;
Usability evaluation
ID PHYSICIANS; INFORETRIEVER; RESOURCES; RETRIEVAL; SETTINGS; COMPUTER
AB Objectives: (1) To develop a prototype Continuity of Care Record (CCR) with context-specific links to electronic HIV information resources; and (2) to assess case managers' perceptions regarding the usability of the prototype.
Methods: We integrated context-specific links to HIV case management information resources into a prototype CCR using the Infobutton Manager and Librarian Infobutton Tailoring Environment (LITE). Case managers (N = 9) completed a think-aloud protocol and the Computer System Usability Questionnaire (CSUQ) to evaluate the usability of the prototype. Verbalizations from the think-aloud protocol were summarized using thematic analysis. CSUQ data were analyzed with descriptive statistics.
Results: Although participants expressed positive comments regarding the usability of the prototype, the think-aloud protocol also identified the need for improvement in resource labels and for additional resources. On a scale ranging from 1 (strongly agree) to 7 (strongly disagree), the average CSUQ overall satisfaction was 2.25 indicating that users (n = 9) were generally satisfied with the system. Mean CSUQ factor scores were: System Usefulness (M = 2.13), Information Quality (M = 2.46), and Interface Quality (M = 2.26).
Conclusion: Our novel application of the Infobutton Manager and LITE in the context of case management for persons living with HIV in community-based settings resulted in a prototype CCR with infobuttons that met the majority of case managers' information needs and received relatively positive usability ratings. Findings from this study inform future integration of context-specific links into CCRs and electronic health records and support their use for meeting end-users information needs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Schnall, Rebecca; Bakken, Suzanne] Columbia Univ, Sch Nursing, New York, NY 10032 USA.
[Cimino, James J.] NIH, Ctr Clin, Lab Informat Dev, Bethesda, MD 20892 USA.
[Bakken, Suzanne] Columbia Univ, Coll Phys & Surg, Dept Biomed Informat, New York, NY USA.
RP Schnall, R (reprint author), Columbia Univ, Sch Nursing, 617 W 168th St, New York, NY 10032 USA.
EM rb897@columbia.edu
OI Cimino, James/0000-0003-4101-1622; Schnall, Rebecca/0000-0003-2184-4045
FU National Institute of Nursing Research [P30NR010677]; Health Resources
and Services Administration Grant [D11HP07346]
FX The authors thank Peter Gordon, MD and Eli Camhi, MSSW, Principal
Investigators of the parent project (New York-Presbyterian
Hospital/Select Health CCD Demonstration Project, H97HA08483), Martha
Rodriguez for her assistance in subject recruitment, and the case
managers who participated in the study. The study was supported by the
National Institute of Nursing Research (P30NR010677) and the Health
Resources and Services Administration Grant (D11HP07346).
NR 34
TC 8
Z9 8
U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1386-5056
J9 INT J MED INFORM
JI Int. J. Med. Inform.
PD AUG
PY 2012
VL 81
IS 8
BP 549
EP 555
DI 10.1016/j.ijmedinf.2012.05.002
PG 7
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA 970FV
UT WOS:000306114400005
PM 22632821
ER
PT J
AU Zimonjic, DB
Popescu, NC
AF Zimonjic, Drazen B.
Popescu, Nicholas C.
TI Role of DLC1 tumor suppressor gene and MYC oncogene in pathogenesis of
human hepatocellular carcinoma: Potential prospects for combined
targeted therapeutics
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE DLC1; tumor suppressor; MYC; oncogene; liver cancer; targeted therapy
ID GTPASE-ACTIVATING PROTEIN; GROWTH-FACTOR-ALPHA; TRANSGENIC MOUSE MODEL;
BREAST-CANCER CELLS; FRIZZLED-RELATED PROTEIN-1; LIVER-CANCER; C-MYC;
FRAGILE SITES; CHROMOSOME 8P; RHO-GTPASES
AB Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, and its incidence is increasing worldwide in an alarming manner. The development of curative therapy for advanced and metastatic HCC is a high clinical priority. The HCC genome is complex and heterogeneous; therefore, the identification of recurrent genomic and related gene alterations is critical for developing clinical applications for diagnosis, prognosis and targeted therapy of the disease. This article focuses on recent research progress and our contribution in identifying and deciphering the role of defined genetic alterations in the pathogenesis of HCC. A significant number of genes that promote or suppress HCC cell growth have been identified at the sites of genomic reorganization. Notwithstanding the accumulation of multiple genetic alterations, highly recurrent changes on a single chromosome can alter the expression of oncogenes and tumor suppressor genes (TSGs) whose deregulation may be sufficient to drive the progression of normal hepatocytes to malignancy. A distinct and highly recurrent pattern of genomic imbalances in HCC includes the loss of DNA copy number (associated with loss of heterozygosity) of TSG-containing chromosome 8p and gain of DNA copy number or regional amplification of protooncogenes on chromosome 8q. Even though 8p is relatively small, it carries an unusually large number of TSGs, while, on the other side, several oncogenes are dispersed along 8q. Compelling evidence demonstrates that DLC1, a potent TSG on 8p, and MYC oncogene on 8q play a critical role in the pathogenesis of human HCC. Direct evidence for their role in the genesis of HCC has been obtained in a mosaic mouse model. Knockdown of DLC1 helps MYC in the induction of hepatoblast transformation in vitro, and in the development of HCC in vivo. Therapeutic interventions, which would simultaneously target signaling pathways governing both DLC1 and MYC functions in hepatocarcinogenesis, could result in progress in the treatment of liver cancer.
C1 [Zimonjic, Drazen B.; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA.
EM popescun@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, NIH
FX This study was supported by the Intramural Research Program of the
National Cancer Institute, NIH.
NR 171
TC 23
Z9 26
U1 0
U2 10
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD AUG
PY 2012
VL 41
IS 2
BP 393
EP 406
DI 10.3892/ijo.2012.1474
PG 14
WC Oncology
SC Oncology
GA 970TE
UT WOS:000306154400001
PM 22580498
ER
PT J
AU Longbottom, ME
Roberts, JN
Tom, M
Hughes, SE
Howard, VJ
Sheffet, AJ
Meschia, JF
Brott, TG
AF Longbottom, Mary E.
Roberts, Jamie N.
Tom, MeeLee
Hughes, Susan E.
Howard, Virginia J.
Sheffet, Alice J.
Meschia, James F.
Brott, Thomas G.
CA CREST Investigators
TI Interventions to increase enrollment in a large multicenter phase 3
trial of carotid stenting vs. endarterectomy
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE carotid endarterectomy; carotid stenosis; carotid stenting; clinical
trial; prevention; stroke
ID CLINICAL-TRIALS; REVASCULARIZATION ENDARTERECTOMY; ARTERY STENOSIS;
STROKE; PREVENTION; CREST
AB Background Randomized clinical trials often encounter slow enrollment. Failing to meet sample size requirements has scientific, financial, and ethical implications. Aims We report interventions used to accelerate recruitment in a large multicenter clinical trial that was not meeting prespecified enrollment commitments. Methods The Carotid Revascularization Endarterectomy vs. Stenting Trial began randomization in December 2000. To accelerate enrollment, multiple recruitment tactics were initiated, which included expanding the number of sites, hiring a recruitment director (May 2003), broadening eligibility criteria (April 2005), branding with a study logo, Web site, and recruitment materials, increasing site visits by study leadership, sending e-mails to the site teams after every enrollment, distributing electronic newsletters, and implementing investigator and coordinator conferences. Results From December 2000 through May 2003, 14 sites became active (54 patients randomized), from June 2003 through April 2005, 44 sites were added (404 patients randomized), and from May 2005 through July 2008, 54 sites were added (2044 patients randomized). During these time intervals, the number of patients enrolled per site per year was 1.5, 3.6, and 5.6. For the single years 2004 to 2008, the mean monthly randomization rates per year were 19.7, 38.1, 56.4, 53.0, and 54.7 (annualized), respectively. Enrollment was highest after recruitment tactics were implemented: 677 patients in 2006, 636 in 2007, and 657 in 2008 (annualized). The prespecified sample size of 2502 patients, 47% asymptomatic, was accomplished on July 2008. Conclusions Aggressive recruitment tactics and investment in a full-time recruitment director who can lead implementation may be effective in accelerating recruitment in multicenter trials.
C1 [Longbottom, Mary E.; Meschia, James F.; Brott, Thomas G.] Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA.
[Roberts, Jamie N.] NINDS, Off Clin Res, NIH, Neurosci Ctr, Bethesda, MD 20892 USA.
[Tom, MeeLee; Hughes, Susan E.; Sheffet, Alice J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Howard, Virginia J.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
RP Brott, TG (reprint author), Mayo Clin Jacksonville, Dept Neurol, Griffin Bldg,3rd Floor,4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM brott.thomas@mayo.edu
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health [R01 NS 038384]; Abbott Vascular Solutions, Inc.
FX This work was supported by the National Institute of Neurological
Disorders and Stroke and the National Institutes of Health (R01 NS
038384); supplemental funding from Abbott Vascular Solutions, Inc.
(formerly Guidant).
NR 18
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
J9 INT J STROKE
JI Int. J. Stroke
PD AUG
PY 2012
VL 7
IS 6
BP 447
EP 453
DI 10.1111/j.1747-4949.2012.00833.x
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 974AM
UT WOS:000306402100006
PM 22631861
ER
PT J
AU Hua, L
Wang, JTL
Ji, X
Malhotra, A
Khaladkar, M
Shapiro, BA
Zhang, KZ
AF Hua, Lei
Wang, Jason T. L.
Ji, Xiang
Malhotra, Ankur
Khaladkar, Mugdha
Shapiro, Bruce A.
Zhang, Kaizhong
TI A METHOD FOR DISCOVERING COMMON PATTERNS FROM TWO RNA SECONDARY
STRUCTURES AND ITS APPLICATION TO STRUCTURAL REPEAT DETECTION
SO JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY
LA English
DT Article
DE RNA secondary structure; pattern discovery; repeat finding
ID MYOTONIC-DYSTROPHY; TANDEM REPEATS; EDIT DISTANCE; TREES; ALIGNMENTS;
ALGORITHMS; SERVER
AB We propose an ab initio method, named DiscoverR, for finding common patterns from two RNA secondary structures. The method works by representing RNA secondary structures as ordered labeled trees and performs tree pattern discovery using an efficient dynamic programming algorithm. DiscoverR is able to identify and extract the largest common substructures from two RNA molecules having different sizes without prior knowledge of the locations and topologies of these substructures. We also extend DiscoverR to find repeated regions in an RNA secondary structure, and apply this extended method to detect structural repeats in the 3'-untranslated region of a protein kinase gene. We describe the biological significance of a repeated hairpin found by our method, demonstrating the usefulness of the method. DiscoverR is implemented in Java; a jar file including the source code of the program is available for download at http://bioinformatics.njit.edu/DiscoverR.
C1 [Hua, Lei; Wang, Jason T. L.; Ji, Xiang] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
[Wang, Jason T. L.] New Jersey Inst Technol, Bioinformat Program, Newark, NJ 07102 USA.
[Malhotra, Ankur] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Khaladkar, Mugdha] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
[Zhang, Kaizhong] Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada.
RP Hua, L (reprint author), New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
EM lh56@njit.edu; wangj@njit.edu; xj25@njit.edu; anmalhotra@ucsd.edu;
mugdhak@pcbi.upenn.edu; shapirbr@mail.nih.gov; kzhang@csd.uwo.ca
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank the anonymous reviewers for their thoughtful comments and
constructive suggestions. This research was supported, in part, by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 25
TC 2
Z9 2
U1 0
U2 7
PU IMPERIAL COLLEGE PRESS
PI LONDON
PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND
SN 0219-7200
J9 J BIOINF COMPUT BIOL
JI J. Bioinform. Comput. Biol.
PD AUG
PY 2012
VL 10
IS 4
AR 1250001
DI 10.1142/S0219720012500011
PG 15
WC Biochemical Research Methods; Computer Science, Interdisciplinary
Applications; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Computer Science; Mathematical &
Computational Biology
GA 973CH
UT WOS:000306329900003
PM 22809414
ER
PT J
AU Mueller, SC
Hardin, MG
Mogg, K
Benson, V
Bradley, BP
Reinholdt-Dunne, ML
Liversedge, SP
Pine, DS
Ernst, M
AF Mueller, Sven C.
Hardin, Michael G.
Mogg, Karin
Benson, Valerie
Bradley, Brendan P.
Reinholdt-Dunne, Marie Louise
Liversedge, Simon P.
Pine, Daniel S.
Ernst, Monique
TI The influence of emotional stimuli on attention orienting and inhibitory
control in pediatric anxiety
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Anxiety; development; children; emotion; orienting; inhibition; bias;
saccade
ID EYE-MOVEMENT; ANTISACCADE TASK; FACIAL EXPRESSIONS; DISORDERS; THREAT;
PERFORMANCE; BIAS; ADOLESCENCE; PREVALENCE; MECHANISMS
AB Background: Anxiety disorders are highly prevalent in children and adolescents, and are associated with aberrant emotion-related attention orienting and inhibitory control. While recent studies conducted with high-trait anxious adults have employed novel emotion-modified antisaccade tasks to examine the influence of emotional information on orienting and inhibition, similar studies have yet to be conducted in youths. Methods: Participants were 22 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed an emotion-modified antisaccade task that was similar to those used in studies of high-trait anxious adults. This task probed the influence of abruptly appearing neutral, happy, angry, or fear stimuli on orienting (prosaccade) or inhibitory (antisaccade) responses. Results: Anxious compared to healthy children showed facilitated orienting toward angry stimuli. With respect to inhibitory processes, threat-related information improved antisaccade accuracy in healthy but not anxious youth. These findings were not linked to individual levels of reported anxiety or specific anxiety disorders. Conclusions: Findings suggest that anxious relative to healthy children manifest enhanced orienting toward threat-related stimuli. In addition, the current findings suggest that threat may modulate inhibitory control during adolescent development.
C1 [Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
[Mueller, Sven C.] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
[Mogg, Karin; Benson, Valerie; Bradley, Brendan P.; Liversedge, Simon P.] Univ Southampton, Sch Psychol, Southampton, Hants, England.
[Reinholdt-Dunne, Marie Louise] Univ Copenhagen, Dept Psychol, Copenhagen, Denmark.
RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, 15K North Dr, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008;
OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271
FU Intramural Research Program of the National Institute of Mental Health
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 39
TC 11
Z9 11
U1 5
U2 40
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD AUG
PY 2012
VL 53
IS 8
BP 856
EP 863
DI 10.1111/j.1469-7610.2012.02541.x
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 972VW
UT WOS:000306310200007
PM 22409260
ER
PT J
AU Khan, S
Reese, TS
Rajpoot, N
Shabbir, A
AF Khan, Shahid
Reese, Thomas S.
Rajpoot, Nasir
Shabbir, Ayisha
TI Spatiotemporal maps of CaMKII in dendritic spines
SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE Smoldyn; Actin cytoskeleton; Photoactivation; Multi-color confocal
microscopy; Wavelet transform; Cultured hippocampal neurons
ID PROTEIN-KINASE-II; LONG-TERM POTENTIATION; F-ACTIN; HIPPOCAMPAL-NEURONS;
MICROSCOPY; DYNAMICS; TRANSLOCATION; ORGANIZATION; ASSOCIATION;
PLASTICITY
AB The calcium calmodulin dependent kinase (CaMKII) is important for long-term potentiation at dendritic spines. Photo-activatable GFP (PaGFP) - CaMKII fusions were used to map CaMKII movements between and within spines in dissociated hippocampal neurons. Photo-activated PaGFP (GFP*) generated in the shaft spread uniformly, but was retained for about 1 s in spines. The differential localization of GFP*-CaMKII isoforms was visualized with hundred nanometer precision frame to frame using de-noising algorithms. GFP*-CaMKII alpha localized to the tips of mushroom spines. The spatiotemporal profiles of native and kinase defective GFP*-CaMKII beta, differed markedly from GFP*-CaMKII alpha and mutant GFP*-CaMKII beta lacking the association domain. CaMKII beta bound to cortical actin in the dendrite and the stable actin network in spine bodies. Glutamate produced a transiently localized GFP*-CaMKII alpha fraction and a soluble GFP*-CaMKII beta fraction in spine bodies. Single molecule simulations of the interplay between diffusion and biochemistry of GFP* species were guided by the spatiotemporal maps and set limits on binding parameters. They highlighted the role of spine morphology in modulating bound CaMKII lifetimes. The long residence times of GFP*-CaMKII beta relative to GFP*-CaMKII alpha followed as consequence of more binding sites on the actin cytoskeleton than the post-synaptic density. These factors combined to retain CaMKII for tens of seconds, sufficient to outlast the calcium transients triggered by glutamate, without invoking complex biochemistry.
C1 [Khan, Shahid; Rajpoot, Nasir; Shabbir, Ayisha] LUMS Sch Sci & Engn, Sect U, DHA, Lahore, Pakistan.
[Khan, Shahid; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Khan, Shahid] Mol Biol Consortium, Chicago, IL 60612 USA.
[Rajpoot, Nasir] Univ Warwick, Computat Biol & Bioimaging Grp, Dept Comp Sci, Coventry CV4 7AL, W Midlands, England.
RP Khan, S (reprint author), LUMS Sch Sci & Engn, Sect U, DHA, Lahore, Pakistan.
EM shahidkh@lums.edu.pk
OI Rajpoot, Nasir/0000-0002-4706-1308
FU LUMS School of Science Engineering
FX We thank Dr Steven Andrews for advice and discussion regarding Smoldyn
and Dr Ayse Dosemici for comments on the manuscript. Ayisha Shabbir was
supported by start-up funds from the LUMS School of Science &
Engineering (to S.K).
NR 46
TC 12
Z9 12
U1 1
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5313
EI 1573-6873
J9 J COMPUT NEUROSCI
JI J. Comput. Neurosci.
PD AUG
PY 2012
VL 33
IS 1
BP 123
EP 139
DI 10.1007/s10827-011-0377-1
PG 17
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA 972PI
UT WOS:000306288900007
PM 22218920
ER
PT J
AU Dallmeier, D
Larson, MG
Wang, N
Fontes, JD
Benjamin, EJ
Fox, CS
AF Dallmeier, Dhayana
Larson, Martin G.
Wang, Na
Fontes, Joao D.
Benjamin, Emelia J.
Fox, Caroline S.
TI Addition of Inflammatory Biomarkers Did Not Improve Diabetes Prediction
in the Community: The Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE biomarkers; C-reactive protein; diabetes; inflammation; prediction
ID C-REACTIVE PROTEIN; INSULIN-RESISTANCE; LIFE-STYLE; ELEVATED LEVELS;
RISK; MELLITUS; ATHEROSCLEROSIS; PREVENTION; AUGSBURG; MARKERS
AB Background-Prior studies have reported conflicting findings with regard to the association of biomarkers in the prediction of incident type 2 diabetes. We evaluated 12 biomarkers as possible diabetes predictors in the Framingham Heart Study.
Methods and Results-Biomarkers representing inflammation (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), endothelial dysfunction (intercellular adhesion molecule-1), vascular damage (CD40-ligand, P-selectin, and lipoprotein-associated phospholipase A2 mass and activity), and oxidative stress (urinary isoprostanes) were measured in participants without diabetes attending the Offspring seventh (n=2499) or multiethnic Omni second (n=189) examination (1998-2001). Biomarkers were log(e) transformed and standardized. Multivariable logistic regression tested each biomarker in association with incident diabetes at a follow-up examination (the Offspring eighth and Omni third examination; mean 6.6 years later), with adjustment for age, sex, cohort, body mass index, fasting glucose, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides, and smoking. C statistics were evaluated with and without inflammatory markers. In 2638 participants (56% women, mean age 59 years), 162 (6.1%) developed type 2 diabetes. All biomarkers, excluding osteoprotegerin, were associated with the outcome with adjustment for age, sex, and cohort; however, none remained significant after multivariable adjustment (all P>0.05). The c statistic from the model including only clinical covariates (0.89) did not statistically significantly improve after addition of biomarkers (all P>0.10).
Conclusions-Biomarkers representing different inflammatory pathways are associated with incident diabetes but do not remain statistically significant after adjustment for established clinical covariates. Inflammatory biomarkers might not be an effective resource to predict type 2 diabetes in community-based samples.
C1 [Dallmeier, Dhayana; Larson, Martin G.; Fontes, Joao D.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Dallmeier, Dhayana] Boston Univ, Sch Med, Div Gen Internal Med, Boston, MA 02215 USA.
[Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM emelia@bu.edu
OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institutes of Health, National Center for
Research Resources, General Clinical Research Centers Program
[M01-RR-01066]; [RO1-HL076784]; [RO1-HL064753]; [R01-AG028321]
FX This study was funded by the National Heart, Lung, and Blood Institute's
Framingham Heart Study N01-HC-25195, and by RO1-HL076784, RO1-HL064753,
and R01-AG028321 (Dr Benjamin), the National Institutes of Health,
National Center for Research Resources, General Clinical Research
Centers Program (Grant Number M01-RR-01066). Lp-PLA2 activity
measurements were provided by GlaxoSmithKline and mass measurements by
diaDexus at no cost to the Framingham Heart Study.
NR 27
TC 15
Z9 15
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD AUG
PY 2012
VL 1
IS 4
AR UNSP e000869
DI 10.1161/JAHA.112.000869
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 243RO
UT WOS:000326334800006
PM 23130155
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI And What About Exercise? Fitness and Risk of Death in "Low-Risk" Adults
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Editorial Material
DE editorials; exercise; risk, low; Framingham Risk Score; cardiovascular
diseases
ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK; PHYSICAL-ACTIVITY;
BLOOD-PRESSURE
C1 [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD USA.
RP Lauer, MS (reprint author), 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
NR 18
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD AUG
PY 2012
VL 1
IS 4
AR UNSP e003228
DI 10.1161/JAHA.112.003228
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 243RO
UT WOS:000326334800015
PM 23130175
ER
PT J
AU Richter, HE
Brubaker, L
Stoddard, AM
Xu, Y
Zyczynski, HM
Norton, P
Sirls, LT
Kraus, SR
Chai, TC
Zimmern, P
Gormley, EA
Kusek, JW
Albo, ME
AF Richter, Holly E.
Brubaker, Linda
Stoddard, Anne M.
Xu, Yan
Zyczynski, Halina M.
Norton, Peggy
Sirls, Larry T.
Kraus, Stephen R.
Chai, Toby C.
Zimmern, Philippe
Gormley, E. Ann
Kusek, John W.
Albo, Michael E.
CA Urinary Incontinence Treatment Net
TI Patient Related Factors Associated with Long-Term Urinary Continence
After Burch Colposuspension and Pubovaginal Fascial Sling Surgeries
SO JOURNAL OF UROLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the American-Urological-Association (AUA)
CY MAY 14-19, 2011
CL Washington, DC
SP Amer Urol Assoc (AUA)
DE urinary incontinence, stress; urinary incontinence, urge; treatment
outcome; surgical procedures, operative
ID STRESS-INCONTINENCE SURGERY; MIXED INCONTINENCE; FOLLOW-UP;
SATISFACTION; ADULTS; IMPACT; TRIAL; WOMEN
AB Purpose: We examined preoperative and postoperative patient related factors associated with continence status up to 7 years after surgery for stress urinary incontinence.
Materials and Methods: Women randomized to Burch colposuspension or fascial sling surgery and assessed for the primary outcome of urinary continence 2 years after surgery were eligible to enroll in a prospective observational study. Survival analysis was used to investigate baseline and postoperative factors in the subsequent risk of stress urinary incontinence, defined as self-report of stress urinary incontinence symptoms, incontinence episodes on a 3-day diary or surgical re-treatment.
Results: Of the women who participated in the randomized trial 74% (482 of 655) were enrolled in the followup study. Urinary continence rates decreased during a period of 2 to 7 years postoperatively from 42% to 13% in the Burch group and from 52% to 27% in the sling group, respectively. Among the baseline factors included in the first multivariable model age (p = 0.03), prior stress urinary incontinence surgery (p = 0.02), menopausal status (0.005), urge index (0.006), assigned surgery (p = 0.01) and recruiting site (p = 0.02) were independently associated with increased risk of incontinence. In the final multivariable model including baseline and postoperative factors, Burch surgery (p = 0.01), baseline variables of prior urinary incontinence surgery (p = 0.04), menopausal status (p = 0.03) and postoperative urge index (p = 0.001) were each significantly associated with a greater risk of recurrent urinary incontinence.
Conclusions: Preoperative and postoperative urgency incontinence symptoms, Burch urethropexy, prior stress urinary incontinence surgery and menopausal status were negatively associated with long-term continence rates. More effective treatment of urgency urinary incontinence in patients who undergo stress urinary incontinence surgery may improve long-term overall continence status.
C1 [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35249 USA.
[Brubaker, Linda] Loyola Univ, Chicago, IL 60611 USA.
[Stoddard, Anne M.; Xu, Yan] New England Res Inst, Watertown, MA 02172 USA.
[Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
[Norton, Peggy] Univ Utah, Salt Lake City, UT USA.
[Sirls, Larry T.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Kraus, Stephen R.] Univ Texas San Antonio, San Antonio, TX USA.
[Zimmern, Philippe] Univ Texas Dallas, Dallas, TX 75230 USA.
[Chai, Toby C.] Univ Maryland, Baltimore, MD 21201 USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Albo, Michael E.] Univ Calif San Diego, La Jolla, CA 92093 USA.
RP Richter, HE (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, 619 19th St S,176 F,Suite 10382, Birmingham, AL 35249 USA.
EM hrichter@uabmc.edu
FU NIDDK NIH HHS [U01 DK060380, U01 DK058229, U01 DK060395, U01 DK60393,
U01 DK060401, U01 DK58231, U01 DK58234, U01 DK60379, U01 DK58225, U01
DK060393, U01 DK60397, U01 DK060379, U01 DK60380, U01 DK060397, U01
DK058234, U01 DK058231, U01 DK058225, U01 DK60401, U01 DK60395, U01
DK58229]
NR 17
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2012
VL 188
IS 2
BP 485
EP 489
DI 10.1016/j.juro.2012.04.010
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 972IM
UT WOS:000306270600046
PM 22704099
ER
PT J
AU Kim, KB
Prieto, V
Joseph, RW
Diwan, AH
Gallick, GE
Papadopoulos, NE
Bedikian, AY
Camacho, LH
Hwu, P
Ng, CS
Wei, W
Johnson, MM
Wittemer, SM
Vardeleon, A
Reckeweg, A
Colevas, AD
AF Kim, Kevin B.
Prieto, Victor
Joseph, Richard W.
Diwan, Abdul H.
Gallick, Gary E.
Papadopoulos, Nicholas E.
Bedikian, Agop Y.
Camacho, Luis H.
Hwu, Patrick
Ng, Chaan S.
Wei, Wei
Johnson, Marcella M.
Wittemer, Sabine M.
Vardeleon, Anna
Reckeweg, Aaron
Colevas, A. Dimitrios
TI A randomized phase II study of cilengitide (EMD 121974) in patients with
metastatic melanoma
SO MELANOMA RESEARCH
LA English
DT Article
DE cilengitide; melanoma; phase II; alpha(v)beta(3) integrin
ID V BETA 3; ALPHA(V)BETA(3) INTEGRIN; CLINICAL-SIGNIFICANCE;
MALIGNANT-MELANOMA; SOLID TUMORS; EXPRESSION; FIBRONECTIN; ANGIOGENESIS;
MATRIX; CELLS
AB Cilengitide (EMD 121974) is a selective inhibitor of integrins alpha(v)beta(3) and alpha(v)beta(5). The alpha(v)beta(3) promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no alpha(v)beta(3) expression at baseline. Overall, alpha(v)beta(3) expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline alpha(v)beta(3) expression. Melanoma Res 22:294-301 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430, Houston, TX 77030 USA.
[Prieto, Victor; Diwan, Abdul H.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Gallick, Gary E.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
[Ng, Chaan S.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA.
[Wei, Wei; Johnson, Marcella M.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Colevas, A. Dimitrios] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Wittemer, Sabine M.] Merck KGaA, Darmstadt, Germany.
RP Kim, KB (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM kkim@mdanderson.org
OI Joseph, Richard/0000-0001-6102-4661
FU National Cancer Institute [N01 CM-17003, N02 CO-12400]; Cancer Center
[CA16672]
FX This work was supported by National Cancer Institute grants N01 CM-17003
and N02 CO-12400 and Cancer Center Support Grant CA16672.
NR 27
TC 22
Z9 24
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0960-8931
J9 MELANOMA RES
JI Melanoma Res.
PD AUG
PY 2012
VL 22
IS 4
BP 294
EP 301
DI 10.1097/CMR.0b013e32835312e4
PG 8
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA 972LJ
UT WOS:000306278300002
PM 22668797
ER
PT J
AU Canelas, MM
Bermejo, JL
Landi, MT
Requena, C
Guillen, C
Kumar, R
Nagore, E
AF Canelas, Maria M.
Bermejo, Justo Lorenzo
Landi, Maria Teresa
Requena, Celia
Guillen, Carlos
Kumar, Rajiv
Nagore, Eduardo
TI Characterization of nonacral melanoma patients without typical risk
factors
SO MELANOMA RESEARCH
LA English
DT Article
DE melanoma; nevus; phenotype; route; sun exposure
ID CUTANEOUS MALIGNANT-MELANOMA; ACRAL LENTIGINOUS MELANOMA; SUN EXPOSURE;
MELANOCYTIC NEVI; METAANALYSIS; ACTIVATION; VARIANTS; PATHWAYS; NUMBER;
SITE
AB A divergent pathway model to cutaneous melanoma is commonly accepted: sun sensitivity/chronic sun exposure and melanocytic instability. Although this dual model explains the development of most melanomas, clinical experience suggests other possible routes. The aim of this study was to explore the characteristics of patients who do not fit with these two pathways. We selected 818 patients with nonacral cutaneous melanoma and defined three groups: nevus-prone individuals, sun-sensitive individuals, and non-nevus-prone and non-sun-sensitive individuals. This group included patients without identifiable melanoma risk factors and comprised 52 patients (5.5% of the overall nonacral melanoma population). These patients were more frequently women, were more likely to present melanoma at a very young age (13.5% before 25 years), to have less frequent personal history of melanoma and remnants of pre-existing nevi, and to present tumors on the trunk and legs. We have identified a group of patients with fewer risk factors for melanoma that needs further studies to increase our understanding of melanoma development. Melanoma Res 22:316-319 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Canelas, Maria M.; Requena, Celia; Guillen, Carlos; Nagore, Eduardo] Inst Valenciano Oncol, Dept Dermatol, E-46009 Valencia, Spain.
[Nagore, Eduardo] Univ Catolica Valencia, Dept Dermatol, Valencia, Spain.
[Bermejo, Justo Lorenzo] Univ Heidelberg Hosp, Inst Med Biometry & Informat, Heidelberg, Germany.
[Bermejo, Justo Lorenzo; Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany.
[Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Nagore, E (reprint author), Inst Valenciano Oncol, Dept Dermatol, C Prof Beltran Baguena 8, E-46009 Valencia, Spain.
EM eduyame@meditex.es
OI Kumar, Rajiv/0000-0002-6093-0395
NR 28
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0960-8931
J9 MELANOMA RES
JI Melanoma Res.
PD AUG
PY 2012
VL 22
IS 4
BP 316
EP 319
DI 10.1097/CMR.0b013e3283541460
PG 4
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA 972LJ
UT WOS:000306278300005
PM 22516967
ER
PT J
AU Cartwright, MS
Hobson-Webb, LD
Boon, AJ
Alter, KE
Hunt, CH
Flores, VH
Werner, RA
Shook, SJ
Thomas, TD
Primack, SJ
Walker, FO
AF Cartwright, Michael S.
Hobson-Webb, Lisa D.
Boon, Andrea J.
Alter, Katharine E.
Hunt, Christopher H.
Flores, Victor H.
Werner, Robert A.
Shook, Steven J.
Thomas, T. Darrell
Primack, Scott J.
Walker, Francis O.
TI EVIDENCE-BASED GUIDELINE: NEUROMUSCULAR ULTRASOUND FOR THE DIAGNOSIS OF
CARPAL TUNNEL SYNDROME
SO MUSCLE & NERVE
LA English
DT Article
DE carpal tunnel syndrome; median nerve; mononeuropathy; nerve conduction
studies; ultrasound
ID CROSS-SECTIONAL AREA; HIGH-RESOLUTION ULTRASONOGRAPHY; BIFID MEDIAN
NERVE; TRAUMATIC NEUROMA; MOTOR BRANCH; GRAY-SCALE; SONOGRAPHY;
CONDUCTION; NEUROPATHY; GANGLION
AB Introduction: The purpose of this study was to develop an evidence-based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). Methods: Two questions were asked: (1) What is the accuracy of median nerve cross-sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). Results: Neuromuscular ultrasound measurement of median nerve cross-sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B). Muscle Nerve 46: 287-293, 2012
C1 [Cartwright, Michael S.; Walker, Francis O.] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA.
[Hobson-Webb, Lisa D.] Duke Univ, Dept Med, Div Neurol, Durham, NC USA.
[Boon, Andrea J.] Mayo Clin, Dept Phys Med & Rehabil, Rochester, MN USA.
[Boon, Andrea J.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Alter, Katharine E.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA.
[Hunt, Christopher H.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Flores, Victor H.] Phys Med Associates, Arlington, TX USA.
[Werner, Robert A.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Shook, Steven J.] Cleveland Clin, Neuromuscular Ctr, Cleveland, OH 44106 USA.
[Thomas, T. Darrell] Knoxville Neurol Specialists, Knoxville, TN USA.
[Primack, Scott J.] Colorado Rehabil & Occupat Med, Aurora, CO USA.
RP Cartwright, MS (reprint author), Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA.
OI Hunt, Christopher/0000-0003-0301-0493
FU NIH/NINDS; Elsevier
FX M.S.C. receives funding from the NIH/NINDS for neuromuscular ultrasound
research and royalties from Elsevier for sales of the textbook
Neuromuscular Ultrasound. F.O.W. receives royalties from Elsevier for
sales of the Neuromuscular Ultrasound.
NR 73
TC 55
Z9 57
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
EI 1097-4598
J9 MUSCLE NERVE
JI Muscle Nerve
PD AUG
PY 2012
VL 46
IS 2
BP 287
EP 293
DI 10.1002/mus.23389
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 975AH
UT WOS:000306478400020
ER
PT J
AU Karlsson, RM
Adermark, L
Molander, A
Perreau-Lenz, S
Singley, E
Solomon, M
Holmes, A
Tanaka, K
Lovinger, DM
Spanagel, R
Heilig, M
AF Karlsson, Rose-Marie
Adermark, Louise
Molander, Anna
Perreau-Lenz, Stephanie
Singley, Erick
Solomon, Matthew
Holmes, Andrew
Tanaka, Kohichi
Lovinger, David M.
Spanagel, Rainer
Heilig, Markus
TI Reduced alcohol intake and reward associated with impaired
endocannabinoid signaling in mice with a deletion of the glutamate
transporter GLAST
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Glutamate transporter; Alcohol; Reward; Endocannabinoid
ID CONDITIONED PLACE PREFERENCE; LONG-TERM DEPRESSION; NUCLEUS-ACCUMBENS;
ETHANOL PREFERENCE; PREFRONTAL CORTEX; LOCOMOTOR STIMULATION; RECEPTOR
ANTAGONIST; AMPHETAMINE REWARD; STRIATAL SYNAPSES; KNOCKOUT MICE
AB A hyperglutamatergic state has been hypothesized to drive escalation of alcohol intake. This hypothesis predicts that an impairment of glutamate clearance through inactivation of the astrocytic glutamate transporter, GLAST (EAAT1), will result in escalation of alcohol consumption. Here, we used mice with a deletion of GLAST to test this prediction. WT and GLAST KO mice were tested for alcohol consumption using two-bottle free-choice drinking. Alcohol reward was evaluated using conditioned place preference (CPP). Sensitivity to depressant alcohol effects was tested using the accelerating rotarod, alcohol-induced hypothermia, and loss of righting reflex. Extracellular glutamate was measured using microdialysis, and striatal slice electrophysiology was carried out to examine plasticity of the cortico-striatal pathway as a model system in which adaptations to the constitutive GLAST deletion can be studied. Contrary to our hypothesis, GLAST KO mice showed markedly decreased alcohol consumption, and lacked CPP for alcohol, despite a higher locomotor response to this drug. Alcohol-induced ataxia, hypothermia, and sedation were unaffected. In striatal slices from GLAST KO mice, long-term depression (LTD) induced by high frequency stimulation, or by post-synaptic depolarization combined with the I.-type calcium channel activator FPL 64176 was absent. In contrast, normal synaptic depression was observed after application of the cannabinoid 1 (CB1) receptor agonist WIN55,212-2. Constitutive deletion of GLAST unexpectedly results in markedly reduced alcohol consumption and preference, associated with markedly reduced alcohol reward. Endocannabinoid signaling appears to be down-regulated upstream of the CBI receptor as a result of the GLAST deletion, and is a candidate mechanism behind the reduction of alcohol reward observed. Published by Elsevier Ltd.
C1 [Karlsson, Rose-Marie; Singley, Erick; Solomon, Matthew; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Adermark, Louise; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Molander, Anna; Perreau-Lenz, Stephanie; Spanagel, Rainer] Univ Mannheim, Cent Inst Mental Hlth, Dept Psychopharmacol, Mannheim, Germany.
[Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Rockville, MD 20852 USA.
[Tanaka, Kohichi] Tokyo Med & Dent Univ, Lab Mol Neurosci, Sch Biomed Sci, Bunkyo Ku, Tokyo, Japan.
[Tanaka, Kohichi] Tokyo Med & Dent Univ, Med Res Inst, Bunkyo Ku, Tokyo, Japan.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
RI Adermark, Louise/D-2297-2014; Perreau-Lenz, Stephanie/D-2309-2014;
OI Adermark, Louise/0000-0002-7165-9908; Perreau-Lenz,
Stephanie/0000-0001-9529-6403; Heilig, Markus/0000-0003-2706-2482
FU National Institute on Alcohol Abuse and Alcoholism Intramural Research
Program; German Bundesministerium fur Bildung und Forschung (NGFN Plus)
[FKZ: 01GS08152]; The Novartis Foundation (Japan) for the promotion of
Science; Takeda Science Foundation; The Tokyo Biochemical Research
Foundation; Research Foundation for Opto-Science and Technology;
Ministry of Education, Culture, Sports, Science, and Technology of Japan
[20022013, 18053006]; Svenska Stiftelsen for Medicinsk Forskning;
Svenska Lakarsallskapet
FX We thank Jessica Mensch for assistance with the breeding at NIAAA and Dr
Yi-Chyan Chen for technical assistance. Authors MH, DML and AH are
supported by the National Institute on Alcohol Abuse and Alcoholism
Intramural Research Program; RS by the German Bundesministerium fur
Bildung und Forschung (NGFN Plus; FKZ: 01GS08152). KT is supported by
The Novartis Foundation (Japan) for the promotion of Science, Takeda
Science Foundation, The Tokyo Biochemical Research Foundation, Research
Foundation for Opto-Science and Technology and by Grants-in-Aids for
Scientific Research on Priority Area (20022013 and 18053006) provided by
the Ministry of Education, Culture, Sports, Science, and Technology of
Japan. AM is supported by Svenska Stiftelsen for Medicinsk Forskning and
Svenska Lakarsallskapet.
NR 56
TC 13
Z9 13
U1 1
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD AUG
PY 2012
VL 63
IS 2
BP 181
EP 189
DI 10.1016/j.neuropharm.2012.01.027
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 972AV
UT WOS:000306249800003
PM 22342743
ER
PT J
AU Kohut, SJ
Decicco-Skinner, KL
Johari, S
Hurwitz, ZE
Baumann, MH
Riley, AL
AF Kohut, Stephen J.
Decicco-Skinner, Kathleen L.
Johari, Shirin
Hurwitz, Zachary E.
Baumann, Michael H.
Riley, Anthony L.
TI Differential modulation of cocaine's discriminative cue by repeated and
variable stress exposure: Relation to monoamine transporter levels
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Cocaine; Drug discrimination; Stress; Monoamine transporters; Western
blotting
ID CHRONIC UNPREDICTABLE STRESS; CHRONIC MILD STRESS; BRAIN REWARD
PATHWAYS; NUCLEUS-ACCUMBENS; RAT-BRAIN; DELTA-FOSB; INDUCED
REINSTATEMENT; DOPAMINE TRANSPORTER; STIMULUS PROPERTIES; RECEPTOR
AGONISTS
AB Discriminative stimulus functions of drugs of abuse play an important role in the acquisition, maintenance and reinstatement of drug-taking behavior. The present study tested whether two different schedules of stressor presentation, i.e., repeated and variable, for 10 days, can modify the discriminative stimulus effects of cocaine in male rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline. Dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporter levels in mesocorticolimbic areas were also measured using western blotting after stress exposure to determine if the relative ratio of these proteins may explain differences in behavior. Rats exposed to both repeated and variable stress displayed shifts in the cocaine dose response curve but with different patterns of responding. In handled controls, ED50 values for cocaine-like responding were stable after 10 days of handling compared to baseline. Repeated stress produced a transient left-ward shift in cocaine-like responding, indicating increased sensitivity to the cocaine cue. ED50 values after variable stress did not differ from baseline, although maximal cocaine-like responding was lower at the two highest doses of cocaine tested at which variably stressed rats exhibited more saline-like responding. Alterations in DAT and NET were found in the Repeated Stress group and DAT and SERT in the Variable Stress group in select brain regions which may be responsible for differences in behavior. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Kohut, Stephen J.; Hurwitz, Zachary E.; Riley, Anthony L.] American Univ, Dept Psychol, Washington, DC 20016 USA.
[Decicco-Skinner, Kathleen L.; Johari, Shirin; Riley, Anthony L.] American Univ, Dept Biol, Washington, DC 20016 USA.
[Baumann, Michael H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Kohut, SJ (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA.
EM steve.kohut@gmail.com
FU Mellon Foundation; NIH
FX This work was supported by a grant from the Mellon Foundation to Anthony
L. Riley, Ph.D. and Kathleen Decicco-Skinner, Ph.D. and NIH Intramural
funds to Michael H. Baumann, Ph.D.
NR 70
TC 6
Z9 6
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD AUG
PY 2012
VL 63
IS 2
BP 330
EP 337
DI 10.1016/j.neuropharm.2012.03.012
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 972AV
UT WOS:000306249800019
PM 22516586
ER
PT J
AU Chew, EY
AF Chew, Emily Y.
TI How Prevalent is Macular Telangiectasia Type 2?
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Editorial Material
C1 NEI, NIH, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0928-6586
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD AUG
PY 2012
VL 19
IS 4
BP 183
EP 184
DI 10.3109/09286586.2012.654844
PG 2
WC Ophthalmology
SC Ophthalmology
GA 971GH
UT WOS:000306191300001
PM 22364719
ER
PT J
AU Schoenebeck, JJ
Hutchinson, SA
Byers, A
Beale, HC
Carrington, B
Faden, DL
Rimbault, M
Decker, B
Kidd, JM
Sood, R
Boyko, AR
Fondon, JW
Wayne, RK
Bustamante, CD
Ciruna, B
Ostrander, EA
AF Schoenebeck, Jeffrey J.
Hutchinson, Sarah A.
Byers, Alexandra
Beale, Holly C.
Carrington, Blake
Faden, Daniel L.
Rimbault, Maud
Decker, Brennan
Kidd, Jeffrey M.
Sood, Raman
Boyko, Adam R.
Fondon, John W., III
Wayne, Robert K.
Bustamante, Carlos D.
Ciruna, Brian
Ostrander, Elaine A.
TI Variation of BMP3 Contributes to Dog Breed Skull Diversity
SO PLOS GENETICS
LA English
DT Article
ID PROTEIN-KINASE-II; CHROMOSOME ASSIGNMENT; GENETIC-ANALYSIS; SELECTIVE
SWEEP; ZEBRAFISH; DIFFERENTIATION; ASSOCIATION; EXPRESSION; SEQUENCE;
DENSITY
AB Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
C1 [Schoenebeck, Jeffrey J.; Byers, Alexandra; Beale, Holly C.; Faden, Daniel L.; Rimbault, Maud; Decker, Brennan; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Hutchinson, Sarah A.; Ciruna, Brian] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada.
[Kidd, Jeffrey M.; Bustamante, Carlos D.] Stanford Sch Med, Dept Genet, Stanford, CA USA.
[Boyko, Adam R.] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA.
[Fondon, John W., III] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
[Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Ciruna, Brian] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
RP Schoenebeck, JJ (reprint author), NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Kidd, Jeffrey/0000-0002-9631-1465; Decker, Brennan/0000-0003-4516-7421;
Ostrander, Elaine/0000-0001-6075-9738
FU NIGMS PRAT; HHMI; Natural Sciences and Engineering Research Council of
Canada; National Human Genome Research Institute; NSF [1021397, 0733033,
0948510]
FX JJS was funded by an NIGMS PRAT postdoctoral fellowship. DLF and BD were
supported by HHMI. This work was supported by funding from the Natural
Sciences and Engineering Research Council of Canada (BC) and the
Intramural Program of the National Human Genome Research Institute (EAO,
JJS, AB, HCB, and MR). The authors gratefully acknowledge grants NSF
(DEB) 1021397 and 0733033 (RKW), and NSF (DEB) 0948510 (ARB, CDB). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 48
TC 41
Z9 42
U1 6
U2 82
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2012
VL 8
IS 8
AR e1002849
DI 10.1371/journal.pgen.1002849
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 002JX
UT WOS:000308529300012
PM 22876193
ER
PT J
AU Mackowick, KM
Heishman, SJ
Wehring, HJ
Liu, F
McMahon, RP
Kelly, DL
AF Mackowick, Kristen M.
Heishman, Stephen J.
Wehring, Heidi J.
Liu, Fang
McMahon, Robert P.
Kelly, Deanna L.
TI Illicit drug use in heavy smokers with and without schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Smoking; Cigarettes; Tobacco; Drug use; Alcohol;
Marijuana
ID SEVERE MENTAL-ILLNESS; SUBSTANCE-ABUSE; NICOTINE DEPENDENCE;
CIGARETTE-SMOKING; UNITED-STATES; TOBACCO USE; ANTIPSYCHOTIC
MEDICATIONS; PSYCHIATRIC-DISORDERS; NARCOTICS ADDICTS; FAGERSTROM TEST
AB Objective: The prevalence of cigarette smoking among people with schizophrenia is greater than that of the general population. Because smoking and use of other drugs covary, we examined illicit drug use in current smokers not trying to quit or reduce their tobacco use. We recruited outpatient participants who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (schizophrenia, n=70) and a control group who had no Axis I psychiatric disorders (control, n=97). During a 2-3-hour session, participants completed demographic and research questionnaires, including the Drug Use Survey (DUS).
Results: Participants with schizophrenia were older than controls (p<0.001) and smoked more cigarettes per day (p=0.01), but did not differ in degree of nicotine dependence. Ever using a drug was similar between the groups, except that significantly more participants with schizophrenia reported ever using hallucinogens (p<0.001) and inhalants (p=0.001). For alcohol, cocaine, and marijuana, fewer participants with schizophrenia were current users, but more participants with schizophrenia were past users (ps<0.0001). Heavy smokers from the general population continued to use illicit drugs throughout their lives, while schizophrenia participants had the highest period of illicit drug use in their 20s.
Conclusions: These data suggest that illicit drug use tends to be high in heavy cigarette smokers, regardless of a schizophrenia diagnosis. However, while illicit drug use is high across the lifespan of heavy smokers in the general population, heavy smokers with schizophrenia use illicit drugs mostly in the first decade of their illness. Published by Elsevier B.V.
C1 [Mackowick, Kristen M.; Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Wehring, Heidi J.; Liu, Fang; McMahon, Robert P.; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
RP Mackowick, KM (reprint author), NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, 200,251 Bayview Blvd,01A840, Baltimore, MD 21224 USA.
EM Kristen.mackowick@nih.gov; Heishman@nih.gov;
hwehring@mprc.umaryland.edu; fliu@mprc.umaryland.edu;
rmcmahon@mprc.umaryland.edu; dkelly@mprc.umaryland.edu
RI McMahon, Robert/C-5462-2009
FU NIH, National Institute on Drug Abuse (NIDA); NIDA Residential Research
Support Services [HHSN271200599091CADB, NO-1DA-5-9909]; NIDA; Janssen
Pharmaceutica; Bristol Myers Squibb
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Drug Abuse (NIDA), and NIDA Residential
Research Support Services Contract HHSN271200599091CADB, NO-1DA-5-9909
(PI: Deanna L. Kelly). Both NIDA funds and personnel supported the
design, study methods, and analysis of this study.; Deanna L. Kelly has
received grant support from Janssen Pharmaceutica and Bristol Myers
Squibb.
NR 75
TC 3
Z9 3
U1 7
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD AUG
PY 2012
VL 139
IS 1-3
BP 194
EP 200
DI 10.1016/j.schres.2012.04.012
PG 7
WC Psychiatry
SC Psychiatry
GA 970JO
UT WOS:000306124400031
PM 22591779
ER
PT J
AU Lim, HK
Yang, M
Lam, W
Xu, F
Chen, J
Xu, YD
Shetty, HU
Yang, K
Silva, J
Evans, DC
AF Lim, Heng-Keang
Yang, Min
Lam, Wing
Xu, Fran
Chen, Jie
Xu, Yaodong
Shetty, H. Umesha
Yang, Ke
Silva, Jose
Evans, David C.
TI Free radical metabolism of raloxifene in human liver microsomes
SO XENOBIOTICA
LA English
DT Article
DE Homodimer; phenoxy radical; CYP3A4; myeloperoxidase; horseradish
peroxidase; Orbitrap; H/D exchange
ID ESTROGEN-RECEPTOR MODULATORS; TIME-DEPENDENT INACTIVATION; IN-VITRO;
MULTIFUNCTIONAL MEDICINES; P450 3A4; IDENTIFICATION; BIOACTIVATION;
SITE; PHARMACOKINETICS; GLUCURONIDATION
AB 1. Raloxifene was metabolized predominantly by CYP3A4 in human liver microsomes to a pair of carbon-carbon (RD1-2) and ether (RD3-4) linked homodimers in an nicotinamide adenine dinucleotide phosphate-dependent manner. The major homodimer formed by human liver microsomes (RD3) was different from the major homodimer formed by peroxidases (RD1).
2. RD1, 3 and 4 were identified by both mass spectrometry (MS) and nuclear magnetic resonance (NMR) as symmetrical carbon-carbon (both carbon 7 from benzo[b]thiopen-6-ol) linked homodimer, asymmetrical ether (oxygen from 4-hydroxyphenyl and carbon 7 from benzo[b]thiopen-6-ol) linked homodimer and asymmetrical ether (oxygen and carbon 7 from benzo[b]thiopen-6-ol) linked homodimer, respectively.
3. The structures of the homodimers RD1, 3 and 4 provided evidence for free radical metabolism of raloxifene by predominantly CYP3A4 in human liver microsomes to oxygen-centered phenoxy radicals from 4-hydroxyphenyl and benzo[b]thiopen-6-ol moieties. Further delocalization to ortho carbon-centered radical was only observed for benzo[b]thiopen-6-ol derived phenoxy radical.
C1 [Lim, Heng-Keang; Xu, Yaodong] Janssen Res & Dev, Drug Safety Sci, Drug Metab & Pharmacokinet, Bioanal, Raritan, NJ 08869 USA.
[Yang, Min] Univ Virginia, Dept Chem, Summer Intern, Charlottesville, VA USA.
[Shetty, H. Umesha] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Ke] Univ Illinois, Dept Biochem, Summer Intern, Urbana, IL 61801 USA.
RP Lim, HK (reprint author), Janssen Res & Dev, Drug Safety Sci, Drug Metab & Pharmacokinet, Bioanal, 1000 Route 202 S, Raritan, NJ 08869 USA.
EM hlim5@its.jnj.com
NR 26
TC 2
Z9 2
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD AUG
PY 2012
VL 42
IS 8
BP 737
EP 747
DI 10.3109/00498254.2012.662306
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 971HG
UT WOS:000306193800004
PM 22375838
ER
PT J
AU Bhatia, P
Bernier, M
Sanghvi, M
Moaddel, R
Schwarting, R
Ramamoorthy, A
Wainer, IW
AF Bhatia, Prateek
Bernier, Michel
Sanghvi, Mitesh
Moaddel, Ruin
Schwarting, Roland
Ramamoorthy, Anuradha
Wainer, Irving W.
TI Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus
in glioblastoma multiforme cells
SO XENOBIOTICA
LA English
DT Article
DE ABC transporters; multidrug resistance; mitoxantrone; small interfering
RNA; confocal microscopy
ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; ABC TRANSPORTERS; FUMITREMORGIN-C;
EXPRESSION; PHOSPHORYLATION; INSIGHTS; TISSUES; BRAIN; BCRP
AB 1. The breast cancer resistance protein (BCRP), an ATP binding cassette (ABC) efflux transporter, plays a role in multiple drug resistance (MDR). Previous studies of the subcellular location of the ABC transporter P-glycoprotein indicated that this protein is expressed in nuclear membranes. This study examines the nuclear distribution of BCRP in seven human-derived glioblastoma (GBM) and astrocytoma cell lines.
2. BCRP expression was observed in the nuclear extracts of 6/7 cell lines. Using the GBM LN229 cell line as a model, nuclear BCRP protein was detected by immunoblotting and confocal laser microscopy. Importantly, nuclear BCRP staining was found in a subpopulation of tumour cells in a human brain GBM biopsy.
3. Mitoxantrone cytotoxicity in the LN229 cell line was determined with and without the BCRP inhibitor fumitremorgin C (FTC) and after downregulation of BCRP with small interfering RNA (siRNA). FTC inhibition of BCRP increased mitoxantrone cytotoxicity with a similar to 7-fold reduction in the IC50 and this effect was further potentiated in the siRNA-treated cells.
4. In conclusion, BCRP is expressed in the nuclear extracts of select GBM and astrocytoma cell lines and in a human GBM tumour biopsy. Its presence in the nucleus of cancer cells suggests new role for BCRP in MDR.
C1 [Bhatia, Prateek; Bernier, Michel; Sanghvi, Mitesh; Moaddel, Ruin; Ramamoorthy, Anuradha; Wainer, Irving W.] NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA.
[Schwarting, Roland] Cooper Univ Hosp, Dept Pathol, Camden, NJ USA.
RP Wainer, IW (reprint author), NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA.
EM wainerir@grc.nia.nih.gov
RI Sanghvi, Mitesh/C-6740-2013;
OI Bernier, Michel/0000-0002-5948-368X
FU Intramural NIH HHS [ZIA AG000296-10]
NR 30
TC 13
Z9 13
U1 0
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD AUG
PY 2012
VL 42
IS 8
BP 748
EP 755
DI 10.3109/00498254.2012.662726
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 971HG
UT WOS:000306193800005
PM 22401348
ER
PT J
AU Erinosho, TO
Moser, RP
Oh, AY
Nebeling, LC
Yaroch, AL
AF Erinosho, Temitope O.
Moser, Richard P.
Oh, April Y.
Nebeling, Linda C.
Yaroch, Amy L.
TI Awareness of the Fruits and Veggies-More Matters campaign, knowledge of
the fruit and vegetable recommendation, and fruit and vegetable intake
of adults in the 2007 Food Attitudes and Behaviors (FAB) Survey
SO APPETITE
LA English
DT Article
DE Fruits and Veggies-More Matters; 5 A Day for Better Health; Fruit and
vegetable intake; Nutrition knowledge; Fruit and vegetable
recommendation
ID NUTRITION KNOWLEDGE; DEMOGRAPHIC VARIATION; PSYCHOSOCIAL FACTORS;
UNITED-STATES; CONSUMPTION; HEALTH; SAMPLE; AMERICANS; BELIEFS; PROGRAM
AB Increased consumption of fruits and vegetables is recommended to reduce chronic disease risk. Few studies have examined awareness of the current fruit and vegetable campaign in the United States, Fruits and Veggies-More Matters. This study assessed awareness of the Fruits and Veggies-More Matters campaign and knowledge of the 7-13 serving recommendation for fruit and vegetable consumption among adults, and determined whether these were associated with fruit and vegetable intake. Cross-sectional data from 3021 adults in the United States' National Cancer Institute's 2007 Food Attitudes and Behaviors Survey were analyzed. Few participants were aware of the Fruits and Veggies-More Matters campaign (2%) and the 7-13 recommendation (6%) for adults. More participants were aware of the former >= 5 A Day campaign (29%) and recommendation (30%). Thirty-nine percent reported consuming >= 5 servings of fruits and vegetables daily. Participants were more likely to consume >= 5 servings of fruits and vegetables/day if they were aware of the 5 A Day/Fruits and Veggies-More Matters campaign, and reported that the recommendation for adults was 5 servings/day. Findings suggest the need to increase awareness of the Fruits and Veggies-More Matters campaign, and the 7-13 recommendation among adults to support high fruit and vegetable intake. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Erinosho, Temitope O.] Univ N Carolina, Dept Nutr, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27599 USA.
[Moser, Richard P.; Nebeling, Linda C.] NCI, Bethesda, MD 20852 USA.
[Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE 68105 USA.
[Oh, April Y.] SAIC Frederick Inc, Natl Canc Inst Frederick, Clin Monitoring Res Program, Frederick, MD 21702 USA.
RP Erinosho, TO (reprint author), Univ N Carolina, Dept Nutr, Ctr Hlth Promot & Dis Prevent, 1700 Martin Luther King Jr Blvd,2nd Floor,CB 7426, Chapel Hill, NC 27599 USA.
EM tope_erinosho@unc.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the United States Government.
NR 34
TC 13
Z9 13
U1 0
U2 21
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
J9 APPETITE
JI Appetite
PD AUG
PY 2012
VL 59
IS 1
BP 155
EP 160
DI 10.1016/j.appet.2012.04.010
PG 6
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 966RP
UT WOS:000305855400022
PM 22524998
ER
PT J
AU Moize, V
Gluck, ME
Torres, F
Andreu, A
Vidal, J
Allison, K
AF Moize, Violeta
Gluck, Marci E.
Torres, Ferran
Andreu, Alba
Vidal, Josep
Allison, Kelly
TI Transcultural adaptation of the Night Eating Questionnaire (NEQ) for its
use in the Spanish population
SO EATING BEHAVIORS
LA English
DT Article
DE Night eating syndrome; Nocturnal ingestion; Eating behavior; Assessment;
Transcultural adaptation
ID BECK DEPRESSION INVENTORY; OBESE-PATIENTS; PREVALENCE; DISORDER;
SURGERY; VERSION; SAMPLE
AB Background: Establishing valid and reliable methods of assessing night eating symptoms is an important goal to maximize identification and treatment of the night eating syndrome (NES). The 14-item Night Eating Questionnaire (NEQ) is the only published and validated assessment instrument but is not yet adapted to Spanish.
Methods: We examined the factor structure, internal consistency and validity of the NEQ in Spanish. The study had 4 phases: a) translation from English to Spanish; b) back-translation from Spanish to English, c) administration of translated version to a Spanish sample, and d) a re-test in 36 participants two weeks later. Reliability, stability, and scale structure were evaluated by Cronbach's alpha, test-re-test, and factor analysis, respectively. Divergent validity was assessed by correlation with the Spanish versions of the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI-II).
Results: Two-hundred forty-four individuals (181 f; BMI 34.3 +/- 10 kg/m(2); age 40.5 +/- 15 y) completed the questionnaire. The mean NEQ score was 12.5 +/- 7. The Cronbach's a coefficient for the total score was 0.79, the intraclass correlation was 0.85, and the factor analysis yielded a similar four factor solution as the original scale. Correlation for the test-re-test total score was 0.86. Total NEQ score was significantly correlated with the BDI-II (r = 0.48 p<0.001), but this correlation was not significant during the test-re-test (r = 0.28, p = 0.10) or with STAI at either time point (0.05, p = 0.40; r = 0.07, p = 0.69, respectively).
Conclusions: The Spanish version of the NEQ demonstrated adequate internal consistency for the majority of domains and excellent reproducibility. There was divergent validity with anxiety and a relationship between night eating and depression. These results suggest that the Spanish-version of the NEQ is an instrument that is valid for use in clinical research. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Moize, Violeta; Andreu, Alba; Vidal, Josep] Hosp Clin Univ, Dept Endocrinol & Nutr, Obes Unit, Barcelona, Spain.
[Gluck, Marci E.] NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Torres, Ferran] Univ Autonoma Barcelona, Sch Med, Biostat Unit, IDIBAPS,Hosp Clin, E-08193 Barcelona, Spain.
[Vidal, Josep] Inst Salud Carlos III, CIBER DEM, Barcelona, Spain.
[Allison, Kelly] Univ Penn, Sch Med, Dept Psychiat, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA.
RP Moize, V (reprint author), Hosp Clin Barcelona, UnidadFunc Obesidad, Villarroel St 170, E-08036 Barcelona, Spain.
EM vmoize@clinic.ub.es
RI Torres, Ferran/D-1296-2011
OI Torres, Ferran/0000-0002-7355-7913
FU Intramural NIH HHS
NR 28
TC 13
Z9 14
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1471-0153
J9 EAT BEHAV
JI Eat. Behav.
PD AUG
PY 2012
VL 13
IS 3
BP 260
EP 263
DI 10.1016/j.eatbeh.2012.02.005
PG 4
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 967TX
UT WOS:000305931800014
PM 22664407
ER
PT J
AU Park, S
Chan, CC
AF Park, Stanley
Chan, Chi-Chao
TI Von Hippel-Lindau Disease (VHL): A need for a murine model with retinal
hemangioblastoma
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE von Hippel-Lindau; Retinal hemangioblastoma; Animal model;
Tumorigenesis; Eye
ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE FACTOR;
GENOTYPE-PHENOTYPE CORRELATION; PRIMARY CILIUM-MAINTENANCE; RECEPTOR
INHIBITOR SU5416; VASCULAR TUMORS; IN-VIVO; CONDITIONAL INACTIVATION;
CONGENITAL POLYCYTHEMIA
AB Von Hippel-Lindau (VHL) disease is a highly penetrant autosomal dominant systemic malignancy that gives rise to cystic and highly vascularized tumors in a constellation of organs. Patients with VHL disease commonly present with hemangioblastomas in the central nervous system and the eye while other manifestations include pheochromocytoma, clear cell renal cell carcinoma, endolymphatic sac tumors of the middle ear, pancreatic cystadenomas, epididymal and broad ligament cystadenomas. Animal models inactivating the VHL gene product in various organ tissues have been constructed over the past 15 years to parse its HIF-associated mechanisms and its link to tumorigenesis. These models, despite advancing our understanding the molecular role of VHL, are by and large unable to recapitulate the more common features of human VHL disease. Up to date, no model exists that develop retinal hemangioblastomas, the most common clinical manifestation. The purpose of this review is: (1) to discuss the need for an ocular VHL model, (2) to review the animal models that recapitulate clinical VHL disease and (3) to propose potential mechanisms of tumorigenesis for the development of ocular VHL.
C1 [Park, Stanley; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Park, Stanley] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
FU NIH
FX This work was supported by the NIH intramural research program.
NR 110
TC 2
Z9 2
U1 0
U2 1
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD AUG
PY 2012
VL 27
IS 8
BP 975
EP 984
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 970BC
UT WOS:000306102100002
PM 22763871
ER
EF