FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Adler-Wailes, DC
Guiney, EL
Wolins, NE
Yanovski, JA
AF Adler-Wailes, Diane C.
Guiney, Evan L.
Wolins, Nathan E.
Yanovski, Jack A.
TI Long-Term Ritonavir Exposure Increases Fatty Acid and Glycerol Recycling
in 3T3-L1 Adipocytes as Compensatory Mechanisms for Increased
Triacylglycerol Hydrolysis
SO ENDOCRINOLOGY
LA English
DT Article
ID HIV PROTEASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; ADIPOSE
TRIGLYCERIDE LIPASE; INSULIN-RESISTANCE; PHOSPHOENOLPYRUVATE
CARBOXYKINASE; GENE-EXPRESSION; STIMULATED LIPOLYSIS; INFECTED MEN;
TISSUE; GLYCERONEOGENESIS
AB Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P < 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P < 0.05) and protein (P < 0.05). Ritonavir increased glycerol (P < 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P < 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P < 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thus increasing FA efflux, and leads to compensatory increases in FA reesterification with glycerol and acylglycerols. These changes in FA metabolism may, in part, explain the increased FA efflux observed in ritonavir-associated lipodystrophy. (Endocrinology 151: 2097-2105, 2010)
C1 [Adler-Wailes, Diane C.; Guiney, Evan L.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv, St Louis, MO 63110 USA.
[Wolins, Nathan E.] Washington Univ, Sch Med, Div Nutr Sci, St Louis, MO 63110 USA.
RP Yanovski, JA (reprint author), NIH, Unit Growth & Obes, Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU National Institutes of Health (NIH) [Z01-HD00641]; National Institute of
Child Health and Human Development (NICHD); U.S. Public Health Service,
Department of Health and Human Services
FX This work was supported by the Intramural Research Program, National
Institutes of Health (NIH), Grant Z01-HD00641 (to J.A.Y.) from National
Institute of Child Health and Human Development (NICHD). J.A.Y. is a
Commissioned Officer in the U.S. Public Health Service, Department of
Health and Human Services.
NR 47
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Z9 7
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 MAY
PY 2010
VL 151
IS 5
BP 2097
EP 2105
DI 10.1210/en.2009-1364
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 586JF
UT WOS:000276902600016
PM 20228169
ER
PT J
AU Sharov, AA
AF Sharov, Alexei A.
TI Functional Information: Towards Synthesis of Biosemiotics and
Cybernetics
SO ENTROPY
LA English
DT Article
DE functional information; biosemiotics; cybernetics; evolution; agent;
origin of life; Umwelt; learning; biological complexity; biological
signal processing
ID EVOLUTION; ORIGIN; GENOME; LIFE
AB Biosemiotics and cybernetics are closely related, yet they are separated by the boundary between life and non-life: biosemiotics is focused on living organisms, whereas cybernetics is applied mostly to non-living artificial devices. However, both classes of systems are agents that perform functions necessary for reaching their goals. I propose to shift the focus of biosemiotics from living organisms to agents in general, which all belong to a pragmasphere or functional universe. Agents should be considered in the context of their hierarchy and origin because their semiosis can be inherited or induced by higher-level agents. To preserve and disseminate their functions, agents use functional information - a set of signs that encode and control their functions. It includes stable memory signs, transient messengers, and natural signs. The origin and evolution of functional information is discussed in terms of transitions between vegetative, animal, and social levels of semiosis, defined by Kull. Vegetative semiosis differs substantially from higher levels of semiosis, because signs are recognized and interpreted via direct code-based matching and are not associated with ideal representations of objects. Thus, I consider a separate classification of signs at the vegetative level that includes proto-icons, proto-indexes, and proto-symbols. Animal and social semiosis are based on classification, and modeling of objects, which represent the knowledge of agents about their body (Innenwelt) and environment (Umwelt).
C1 NIA, Baltimore, MD 21224 USA.
RP Sharov, AA (reprint author), NIA, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sharoval@mail.nih.gov
FU National Institute on Aging, NIH
FX I would like to thank Kalevi Kull, Tartu University, for inspiring this
work; and Soren Brier, Copenhagen Business School, for valuable comments
on the philosophic foundations of cybersemiotics. This work was
supported by the Intramural Research Program of the National Institute
on Aging, NIH.
NR 64
TC 17
Z9 17
U1 0
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1099-4300
J9 ENTROPY-SWITZ
JI Entropy
PD MAY
PY 2010
VL 12
IS 5
BP 1050
EP 1070
DI 10.3390/e12051050
PG 21
WC Physics, Multidisciplinary
SC Physics
GA 601VB
UT WOS:000278092100004
PM 22368439
ER
PT J
AU Crump, KS
Chen, C
Chiu, WA
Louis, TA
Portier, CJ
Subramaniam, RP
White, PD
AF Crump, Kenny S.
Chen, Chao
Chiu, Weihsueh A.
Louis, Thomas A.
Portier, Christopher J.
Subramaniam, Ravi P.
White, Paul D.
TI What Role for Biologically Based Dose-Response Models in Estimating
Low-Dose Risk?
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE biologically based dose response; dose-response model; low-dose risk;
risk assessment; two-stage model
ID ALTERED LIVER FOCI; LUNG-CANCER; QUANTITATIVE-ANALYSIS;
SENSITIVITY-ANALYSIS; FORMALDEHYDE; CARCINOGENESIS; RAT;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; DIETHYLNITROSAMINE; PROBABILITY
AB BACKGROUND: Biologically based dose-response (BBDR) models can incorporate data on biological processes at the cellular and molecular level to link external exposure to an adverse effect.
Objectives: Our goal was to examine the utility of BBDR models in estimating low-dose risk. METHODS: We reviewed the utility of BBDR models in risk assessment.
RESULTS: BBDR models have been used profitably to evaluate proposed mechanisms of toxicity and identify data gaps. However, these models have not improved the reliability of quantitative predictions of low-dose human risk. In this commentary we identify serious impediments to developing BBDR models for this purpose. BBDR models do not eliminate the need for empirical modeling of the relationship between dose and effect, but only move it from the whole organism to a lower level of biological organization. However, in doing this, BBDR models introduce significant new sources of uncertainty. Quantitative inferences are limited by inter- and intraindividual heterogeneity that cannot be eliminated with available or reasonably anticipated experimental techniques. BBDR modeling does not avoid uncertainties in the mechanisms of toxicity relevant to low-level human exposures. Although implementation of BBDR models for low-dose risk estimation have thus far been limited mainly to cancer modeled using a two-stage clonal expansion framework, these problems are expected to be present in all attempts at BBDR modeling.
CONCLUSIONS: The problems discussed here appear so intractable that we conclude that BBDR models are unlikely to be fruitful in reducing uncertainty in quantitative estimates of human risk from low-level exposures in the foreseeable future. Use of in vitro data from recent advances in molecular toxicology in BBDR models is not likely to remove these problems and will introduce new issues regarding extrapolation of data from in vitro systems.
C1 [Crump, Kenny S.] Louisiana Tech Univ, Ruston, LA 71272 USA.
[Chen, Chao; Chiu, Weihsueh A.; Subramaniam, Ravi P.; White, Paul D.] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[Louis, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Portier, Christopher J.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Crump, KS (reprint author), Louisiana Tech Univ, Railroad Ave,372 GT Madison Hall,POB 10348, Ruston, LA 71272 USA.
EM kennycrump@email.com
RI Portier, Christopher/A-3160-2010
OI Portier, Christopher/0000-0002-0954-0279
FU National Center for Environmental Assessment, U.S. Environmental
Protection Agency (EPA), through the Oak Ridge Institute for Science and
Education
FX The work performed by K.S.C. was supported by an appointment to the
Research Participation Program of the National Center for Environmental
Assessment, U.S. Environmental Protection Agency (EPA), through the Oak
Ridge Institute for Science and Education.
NR 43
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U1 1
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 MAY
PY 2010
VL 118
IS 5
BP 585
EP 588
DI 10.1289/ehp.0901249
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 598OF
UT WOS:000277846800019
PM 20056564
ER
PT J
AU La Merrill, M
Harper, R
Birnbaum, LS
Cardiff, RD
Threadgill, DW
AF La Merrill, Michele
Harper, Rachel
Birnbaum, Linda S.
Cardiff, Robert D.
Threadgill, David W.
TI Maternal Dioxin Exposure Combined with a Diet High in Fat Increases
Mammary Cancer Incidence in Mice
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE COMT; CYP1B1; dioxin; high-fat diet; mammary cancer; puberty
ID CATECHOL-O-METHYLTRANSFERASE; BREAST-CANCER; DEVELOPMENTAL EXPOSURE;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ESTROGEN BIOACTIVATION;
GENETIC POLYMORPHISMS; MESSENGER-RNA; RAT; RISK; EXPRESSION
AB BACKGROUND: Results from previous studies have suggested that breast cancer risk correlates with total lifetime exposure to estrogens and that early-life 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD) exposure or diets high in fat can also increase cancer risk.
OBJECTIVES: Because both TCDD and diet affect the estrogen pathway, we examined how TCDD and a high-fat diet (HFD) interact to alter breast cancer susceptibility.
METHODS: We exposed pregnant female FVB/NJ mice (12.5 days post-coitus) to 1 mu g/kg TCDD or vehicle; at parturition, the dams were randomly assigned to a low-fat diet (LFD) or a high-fat diet (HFD). Female offspring were maintained on the same diets after weaning and were exposed to 7,12-dimethylbenz[a]anthracene on post-natal days (PNDs) 35, 49, and 63 to initiate mammary tumors. A second cohort of females was treated identically until PND35 or PND49, when mammary gland morphology was examined, or PND50, when mammary gland mRNA was analyzed.
RESULTS: We found that maternal TCDD exposure doubled mammary tumor incidence only in mice fed the HFD. Among HFD-fed mice, maternal TCDD exposure caused rapid mammary development with increased Cyp1b1 (cytochrome P450 1B1) expression and decreased Comt (catechol-O-methyltransferase) expression in mammary tissue. Maternal TCDD exposure also increased mammary tumor Cyp1b1 expression.
CONCLUSIONS: Our data suggest that the HFD increases sensitivity to maternal TCDD exposure, resulting in increased breast cancer incidence, by changing metabolism capability. These results provide a mechanism to explain epidemiological data linking early-life TCDD exposure and diets high in fat to increased risk for breast cancer in humans.
C1 [Threadgill, David W.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA.
[La Merrill, Michele; Harper, Rachel; Threadgill, David W.] Univ N Carolina, Dept Genet, Ctr Environm & Hlth Susceptibil, Lineberger Canc Ctr,Curriculum Toxicol, Chapel Hill, NC USA.
[Birnbaum, Linda S.] US EPA, Expt Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Birnbaum, Linda S.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Cardiff, Robert D.] Univ Calif Davis, Ctr Comparat Med, Dept Pathol & Lab Med, Davis, CA 95616 USA.
RP Threadgill, DW (reprint author), N Carolina State Univ, Dept Genet, CB 7614, Raleigh, NC 27695 USA.
EM threadgill@ncsu.edu
RI Threadgill, David/N-4425-2013
OI Threadgill, David/0000-0003-3538-1635
FU National Institutes of Health (NIH) [CA105417, CA016086, ES010126]; U.S.
Department of Defense [BC050873]
FX This work was supported by National Institutes of Health (NIH) grant
CA105417 (D.W.T.), NIH center grants CA016086 and ES010126, and U.S.
Department of Defense fellowship BC050873 (M.L.M.).
NR 62
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U1 0
U2 3
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
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2010
VL 118
IS 5
BP 596
EP 601
DI 10.1289/ehp.0901047
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 598OF
UT WOS:000277846800021
PM 20435547
ER
PT J
AU Birnbaum, LS
Stokes, WS
AF Birnbaum, Linda S.
Stokes, William S.
TI ICCVAM: Not Doing Enough Response
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
C1 [Birnbaum, Linda S.; Stokes, William S.] NIEHS, NTP Integrency Ctr Evaluat Alternat Toxicol Metho, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NTP, NIH, US Dept HHS, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, NTP Integrency Ctr Evaluat Alternat Toxicol Metho, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbauml@niehs.nih.gov; stokes@niehs.nih.gov
NR 6
TC 0
Z9 0
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 MAY
PY 2010
VL 118
IS 5
BP A195
EP A196
DI 10.1289/ehp.1001969R
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 598OF
UT WOS:000277846800005
ER
PT J
AU Lioy, PJ
Isukapalli, SS
Trasande, L
Thorpe, L
Dellarco, M
Weisel, C
Georgopoulos, PG
Yung, C
Alimokhtari, S
Brown, M
Landrigan, PJ
AF Lioy, Paul J.
Isukapalli, Sastry S.
Trasande, Leonardo
Thorpe, Lorna
Dellarco, Michael
Weisel, Clifford
Georgopoulos, Panos G.
Yung, Christopher
Alimokhtari, Shahnaz
Brown, Margot
Landrigan, Philip J.
TI Using National and Local Extant Data to Characterize Environmental
Exposures in the National Children's Study: Queens County, New York (vol
117, pg 1494, 2009)
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Correction
C1 [Lioy, Paul J.; Isukapalli, Sastry S.; Weisel, Clifford; Georgopoulos, Panos G.; Yung, Christopher; Alimokhtari, Shahnaz] Univ Med & Dent, Environm & Occupat Hlth Sci Inst, New Jersey Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Lioy, Paul J.; Isukapalli, Sastry S.; Weisel, Clifford; Georgopoulos, Panos G.; Yung, Christopher; Alimokhtari, Shahnaz] Rutgers State Univ, Piscataway, NJ USA.
[Trasande, Leonardo; Landrigan, Philip J.] Mt Sinai Sch Med, New York, NY USA.
[Thorpe, Lorna] New York City Dept Hlth & Mental Hyg, New York, NY USA.
[Dellarco, Michael; Brown, Margot] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, NIH, US Dept HHS, Bethesda, MD USA.
RP Lioy, PJ (reprint author), Univ Med & Dent, Environm & Occupat Hlth Sci Inst, New Jersey Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
RI Lioy, Paul/F-6148-2011
NR 1
TC 0
Z9 0
U1 0
U2 0
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 MAY
PY 2010
VL 118
IS 5
BP A197
EP A197
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 598OF
UT WOS:000277846800008
ER
PT J
AU Jusko, TA
De Roos, AJ
Schwartz, SM
Lawrence, BP
Palkovicova, L
Nemessanyi, T
Drobna, B
Fabisikova, A
Kocan, A
Sonneborn, D
Jahnova, E
Kavanagh, TJ
Trnovec, T
Hertz-Picciotto, I
AF Jusko, Todd A.
De Roos, Anneclaire J.
Schwartz, Stephen M.
Lawrence, B. Paige
Palkovicova, Lubica
Nemessanyi, Tomas
Drobna, Beata
Fabisikova, Anna
Kocan, Anton
Sonneborn, Dean
Jahnova, Eva
Kavanagh, Terrance J.
Trnovec, Tomas
Hertz-Picciotto, Irva
TI A cohort study of developmental polychlorinated biphenyl (PCB) exposure
in relation to post-vaccination antibody response at 6-months of age
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE B-cell; Directed acyclic graph; Slovakia; Roma; Epidemiology; Biomarker;
Infant
ID TETANUS TOXOID CONJUGATE; ORGANOCHLORINE PESTICIDES; EASTERN SLOVAKIA;
ENVIRONMENTAL EXPOSURE; MATERNAL IMMUNIZATION; IMMUNE FUNCTION; INFANTS;
SERUM; IMMUNOTOXICITY; CHILDREN
AB Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study.
Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age.
Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener.
Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age. Published by Elsevier Inc.
C1 [Jusko, Todd A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Jusko, Todd A.; De Roos, Anneclaire J.; Schwartz, Stephen M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[De Roos, Anneclaire J.; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
[Lawrence, B. Paige] Univ Rochester, Dept Environm Med, Sch Med & Dent, Rochester, NY USA.
[Palkovicova, Lubica] Slovak Med Univ, Dept Environm Med, Bratislava, Slovakia.
[Nemessanyi, Tomas; Jahnova, Eva] Slovak Med Univ, Dept Immunol & Immunotoxicol, Bratislava, Slovakia.
[Drobna, Beata; Fabisikova, Anna; Kocan, Anton; Trnovec, Tomas] Slovak Med Univ, Dept Tox Organ Pollutants, Bratislava, Slovakia.
[Sonneborn, Dean; Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Kavanagh, Terrance J.] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
RP Jusko, TA (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr,Rall Bld, Res Triangle Pk, NC 27709 USA.
EM juskota@niehs.nih.gov
FU National Institutes of Health [T32-ES007262, T32-RR023256, U01-ES016127,
R01-CA096525]; National Institutes of Health, National Institute of
Environmental Health Sciences; University of Washington, Department of
Epidemiology; US State Department
FX This research received support from National Institutes of Health grants
T32-ES007262, T32-RR023256, U01-ES016127, and R01-CA096525 and from the
Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences. Support was also
provided by a dissertation award from the University of Washington,
Department of Epidemiology and a Fulbright Grant from the US State
Department. This work is solely the responsibility of the authors and
does not necessarily represent the official views of the NIH.
NR 43
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U1 2
U2 8
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 MAY
PY 2010
VL 110
IS 4
BP 388
EP 395
DI 10.1016/j.envres.2010.02.010
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 589ZC
UT WOS:000277191700011
PM 20378105
ER
PT J
AU de Gonzalez, AB
AF de Gonzalez, Amy Berrington
TI Sample-size Efficiencies via the Multiple-Primary-Cancer Study Why Fewer
Cases May Not Mean Less Work
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID BREAST-CANCER; MUTATIONS; MELANOMA; RISK
C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2010
VL 21
IS 3
BP 373
EP 375
DI 10.1097/EDE.0b013e3181d74c08
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 588LL
UT WOS:000277071500013
ER
PT J
AU Ward, MH
Kilfoy, BA
Weyer, PJ
Anderson, KE
Folsom, AR
Cerhan, JR
AF Ward, Mary H.
Kilfoy, Briseis A.
Weyer, Peter J.
Anderson, Kristin E.
Folsom, Aaron R.
Cerhan, James R.
TI Nitrate Intake and the Risk of Thyroid Cancer and Thyroid Disease
SO EPIDEMIOLOGY
LA English
DT Article
ID DRINKING-WATER NITRATE; UNITED-STATES; DIETARY NITRATE; OLDER WOMEN;
HEALTH; CONTAMINATION; GLAND; PERCHLORATE; GROUNDWATER; SYMPORTER
AB Background: Nitrate is a contaminant of drinking water in agricultural areas and is found at high levels in some vegetables. Nitrate competes with uptake of iodide by the thyroid, thus potentially affecting thyroid function.
Methods: We investigated the association of nitrate intake from public water supplies and diet with the risk of thyroid cancer and self-reported hypothyroidism and hyperthyroidism in a cohort of 21,977 older women in Iowa who were enrolled in 1986 and who had used the same water supply for >10 years. We estimated nitrate ingestion from drinking water using a public database of nitrate measurements (1955-1988). Dietary nitrate intake was estimated using a food frequency questionnaire and levels from the published literature. Cancer incidence was determined through 2004.
Results: We found an increased risk of thyroid cancer with higher average nitrate levels in public water supplies and with longer consumption of water exceeding 5 mg/L nitrate-N (for >= 5 years at >5 mg/L, relative risk [RR] = 2.6 [95% confidence interval (CI) = 1.1-6.2]). We observed no association with prevalence of hypothyroidism or hyperthyroidism. Increasing intake of dietary nitrate was associated with an increased risk of thyroid cancer (highest vs. lowest quartile, RR = 2.9 [1.0-8.1]; P for trend = 0.046) and with the prevalence of hypothyroidism (odds ratio = 1.2 [95% CI = 1.1-1.4]), but not hyperthyroidism.
Conclusions: Nitrate may play a role in the etiology of thyroid cancer and warrants further study.
C1 [Ward, Mary H.; Kilfoy, Briseis A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Weyer, Peter J.] Univ Iowa, Ctr Hlth Effects Environm Contaminat, Iowa City, IA USA.
[Anderson, Kristin E.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Cerhan, James R.] Mayo Clin, Div Epidemiol, Coll Med, Rochester, MN USA.
RP Ward, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8006, Bethesda, MD 20892 USA.
EM wardm@mail.nih.gov
RI Aschebrook-Kilfoy, Briseis/A-2537-2012;
OI Cerhan, James/0000-0002-7482-178X
FU NIH/National Cancer Institute; [R01 CA39742]
FX Supported in part by the Intramural Research Program of the NIH/National
Cancer Institute. The Iowa Women's Health Study was supported by grant
R01 CA39742.
NR 36
TC 60
Z9 61
U1 5
U2 24
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2010
VL 21
IS 3
BP 389
EP 395
DI 10.1097/EDE.0b013e3181d6201d
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 588LL
UT WOS:000277071500017
PM 20335813
ER
PT J
AU Sleeman, J
Steeg, PS
AF Sleeman, Jonathan
Steeg, Patricia S.
TI Cancer metastasis as a therapeutic target
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Cancer; Metastasis; Translational research
ID BREAST-CANCER; TUMOR-METASTASIS; BEVACIZUMAB; PROGRESSION; PACLITAXEL;
LESIONS; CELLS
AB Despite many years of basic and clinical research aimed at curbing tumour growth, metastasis remains the prime reason why cancer patients succumb to their disease. Effective translational research is urgently required, yet is not always easy to achieve. Here we review reasons why metastasis as a disease process has proven difficult to control, and suggest ways in which translational research in this area can be strengthened and advanced. Published by Elsevier Ltd.
C1 [Steeg, Patricia S.] NCI, Womens Cancers Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sleeman, Jonathan] Univ Heidelberg, Univ Med Mannheim, D-68167 Mannheim, Germany.
[Sleeman, Jonathan] Inst Genet & Toxikol, Karlsruher Inst Technol, D-76021 Karlsruhe, Germany.
RP Steeg, PS (reprint author), NCI, Womens Cancers Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Sleeman, Jonathan/H-2515-2013
FU European Union [HEALTH-F2-2008-201662]; National Cancer Institute, USA
FX J.P.S. gratefully acknowledges funding from the European Union under the
auspices of the FP7 collaborative project TWIG, Contract No.
HEALTH-F2-2008-201662. P.S.S. is supported by the Intramural Program of
the National Cancer Institute, USA.
NR 24
TC 85
Z9 87
U1 2
U2 18
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 7
SI SI
BP 1177
EP 1180
DI 10.1016/j.ejca.2010.02.039
PG 4
WC Oncology
SC Oncology
GA 599JF
UT WOS:000277906900001
PM 20307970
ER
PT J
AU Barkan, D
Green, JE
Chambers, AF
AF Barkan, Dalit
Green, Jeffrey E.
Chambers, Ann F.
TI Extracellular matrix: A gatekeeper in the transition from dormancy to
metastatic growth
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Cell adhesion; Collagen; Cytoskeleton; Extracellular matrix;
Fibronectins; Integrins; Metalloproteases; Neoplasm metastasis;
Neoplasms; Recurrence
ID INVASIVE DUCTAL CARCINOMA; BREAST-CANCER; GENE-EXPRESSION; TUMOR
DORMANCY; BASEMENT-MEMBRANE; IN-VIVO; 3-DIMENSIONAL CULTURE;
PREMETASTATIC NICHE; CELLULAR SENESCENCE; MALIGNANT PHENOTYPE
AB Metastases can develop after apparently successful treatment of a primary tumour, sometimes following a period of tumour dormancy that can last for years. However, factors that regulate metastatic tumour dormancy remain poorly understood. Here we review the Potential contribution of interactions between tumour cells and the microenvironment in metastatic sites, in regulating tumour dormancy vs. metastatic growth. We focus particularly on the potential role of the extracellular matrix (ECM) in regulating maintenance and release from dormancy. Tumour cells that fail to properly adhere to the ECM may enter a state of dormancy. The molecular and physical composition of the ECM can be affected by tumour cells themselves, as well as multiple stromal cell types. The roles of integrins, fibronectin, and collagen are discussed, as are factors that can change the ECM. A better understanding of the molecular details of the crosstalk between tumour cells and the ECM in secondary sites, and how these regulate the dormant state, may lead to improved therapeutic strategies to induce or maintain disseminated tumour cells in a dormant state, or alternatively to successfully eradicate dormant cells. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Barkan, Dalit] Univ Haifa, Dept Biol, Fac Sci, IL-31999 Haifa, Israel.
[Barkan, Dalit; Green, Jeffrey E.] NCI, Lab Cell Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Chambers, Ann F.] Univ Western Ontario, London Reg Canc Program, London, ON N6A 4L6, Canada.
[Chambers, Ann F.] Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada.
RP Barkan, D (reprint author), Univ Haifa, Dept Biol, Fac Sci, IL-31999 Haifa, Israel.
EM dalitbrk@gmail.com
RI Chambers, Ann/L-6285-2015
OI Chambers, Ann/0000-0002-9509-5123
FU National Institutes of Health; Center for Cancer Research; National
Cancer Institute and National Dental Institute; Canadian Institutes of
Health Research [42511]
FX Grant support: Intramural Program of the National Institutes of Health,
Center for Cancer Research, National Cancer Institute and National
Dental Institute, NIH, and the Canadian Institutes of Health Research
Grant #42511. A.F.C. is Canada Research Chair in Oncology.
NR 74
TC 141
Z9 144
U1 4
U2 32
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 7
SI SI
BP 1181
EP 1188
DI 10.1016/j.ejca.2010.02.027
PG 8
WC Oncology
SC Oncology
GA 599JF
UT WOS:000277906900002
PM 20304630
ER
PT J
AU Gril, B
Evans, L
Palmieri, D
Steeg, PS
AF Gril, Brunilde
Evans, Lynda
Palmieri, Diane
Steeg, Patricia S.
TI Translational research in brain metastasis is identifying molecular
pathways that may lead to the development of new therapeutic strategies
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Brain; Metastases; Breast; Lung
ID CENTRAL-NERVOUS-SYSTEM; CELL LUNG-CANCER; PROPHYLACTIC CRANIAL
IRRADIATION; NEGATIVE BREAST-CANCER; ANTIANGIOGENIC THERAPY; CEREBRAL
METASTASES; CNS METASTASES; RISK-FACTORS; N-CADHERIN; EXPRESSION
AB Central nervous system (CNS) or brain metastasis is an emerging area of interest in organ-specific metastasis research. Lung and breast cancers are the most common types of primary tumors to develop brain metastases. This disease complication contributes significantly to the morbidity and mortality of both of these common cancers; as such, brain metastasis is designated an unmet medical need by the US Food and Drug Administration (FDA). Recently, an increase in incidence of CNS disease has been noted in the literature for breast cancer, while it has been an ongoing major complication from lung cancer. Progress in treating brain metastases has been hampered by a lack of model systems, a lack of human tissue samples, and the exclusion of brain metastatic patients from many clinical trials. While each of those is significant, the major impediment to effectively treating brain metastatic disease is the blood-brain barrier (BBB). This barrier excludes most chemotherapeutics from the brain and creates a sanctuary site for metastatic tumors. Recent findings on the biology of this disease and translational leads identified by molecular studies are discussed in this article. Published by Elsevier Ltd.
C1 [Gril, Brunilde; Evans, Lynda; Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Gril, B (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
EM grilbrun@mail.nih.gov
RI Palmieri, Diane/B-4258-2015
FU National Cancer Institute (NCI)
FX This work was supported by the intramural program of the National Cancer
Institute (NCI).
NR 65
TC 34
Z9 35
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 7
SI SI
BP 1204
EP 1210
DI 10.1016/j.ejca.2010.02.033
PG 7
WC Oncology
SC Oncology
GA 599JF
UT WOS:000277906900005
PM 20303257
ER
PT J
AU Cecchi, F
Rabe, DC
Bottaro, DP
AF Cecchi, Fabiola
Rabe, Daniel C.
Bottaro, Donald P.
TI Targeting the HGF/Met signalling pathway in cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Hepatocyte growth factor; Met; Cancer drug development
ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER;
ACTIVITY IN-VIVO; C-MET RECEPTOR; HEPARAN-SULFATE; LIVER-REGENERATION;
FACTOR ISOFORMS; TPR-MET; THERAPEUTIC INHIBITION
AB Under normal conditions, hepatocyte growth factor (HGF)-induced Met tyrosine kinase (TK) activation is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalisation and degradation. Despite these controls, HGF/Met signalling contributes to oncogenesis and tumour progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumour metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programmes. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signalling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control. (C) 2010 Published by Elsevier Ltd.
C1 [Cecchi, Fabiola; Rabe, Daniel C.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cecchi, F (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10 CRC Rm 1W-5832,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA.
EM cecchif@mail.nih.gov
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Cecchi, Franco/0000-0002-2035-5621
FU NIH, National Cancer Institute, Center for Cancer Research
FX Web site addresses are provided as an informational resource, not as an
endorsement of any product or manufacturer. This work was supported by
the Intramural Research Programme of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 107
TC 107
Z9 117
U1 1
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 7
SI SI
BP 1260
EP 1270
DI 10.1016/j.ejca.2010.02.028
PG 11
WC Oncology
SC Oncology
GA 599JF
UT WOS:000277906900011
PM 20303741
ER
PT J
AU Marshall, JC
Collins, J
Marino, N
Steeg, P
AF Marshall, Jean-Claude
Collins, Joshua
Marino, Natascia
Steeg, Patricia
TI The Nm23-H1 metastasis suppressor as a translational target
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Nm23-H1; Metastasis
ID LYSOPHOSPHATIDIC ACID RECEPTOR; BREAST-CARCINOMA CELLS;
MEDROXYPROGESTERONE ACETATE; KINASE SUPPRESSOR; HISTIDINE KINASES;
GENE-EXPRESSION; YOUNG-WOMEN; CANCER; MOTILITY; CHEMOTHERAPY
AB Nm23 was the first of what has become a field of over 20 known metastasis suppressor genes (MSGs). Since the discovery of Nm23 in 1988, a variety of mechanisms have been attributed to its activity, including a histidine kinase activity, binding of other proteins to regulate metastatic formation, and altered gene expression downstream of Nm23. Here, we will review current efforts to translate the previous work done on this MSG into the clinic, including high-dose medroxyprogesterone acetate (MPA), which has been shown to upregulate Nm23 expression. In addition, we will detail a new potential target downstream of Nm23. LPA1 is one of a group of known cell surface receptors for lysophosphatidic acid (LPA), which has been shown to be inversely correlated with Nm23 expression. A specific LPA1 antagonist could conceivably mimic the effects of Nm23 by downregulating the activity of the LPA1 pathway, which would be of considerable interest for potential clinical use. Published by Elsevier Ltd.
C1 [Marshall, Jean-Claude; Collins, Joshua; Marino, Natascia; Steeg, Patricia] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Marshall, JC (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, 37 Convent Dr,Room 1122, Bethesda, MD 20892 USA.
EM marshallje@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 29
Z9 34
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 7
SI SI
BP 1278
EP 1282
DI 10.1016/j.ejca.2010.02.042
PG 5
WC Oncology
SC Oncology
GA 599JF
UT WOS:000277906900013
PM 20304626
ER
PT J
AU Saul, H
Steeg, P
AF Saul, Helen
Steeg, Patricia
TI Halting metastasis: a new possibility in the clinic
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Editorial Material
C1 [Steeg, Patricia] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2010
VL 46
IS 8
BP 1295
EP 1295
PG 1
WC Oncology
SC Oncology
GA 608UJ
UT WOS:000278611200011
ER
PT J
AU Kataja-Tuomola, M
Sundell, J
Mannisto, S
Virtanen, MJ
Kontto, J
Albanes, D
Virtamo, J
AF Kataja-Tuomola, Merja
Sundell, Jari
Mannisto, Satu
Virtanen, Mikko J.
Kontto, Jukka
Albanes, Demetrius
Virtamo, Jarmo
TI Short-term weight change and fluctuation as risk factors for type 2
diabetes in Finnish male smokers
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Cohort study; Diabetes; Weight change; Weight fluctuation
ID MIDDLE-AGED MEN; BODY-MASS INDEX; LIFE-STYLE; CIGARETTE-SMOKING;
OVERWEIGHT ADULTS; MALE PHYSICIANS; BETA-CAROTENE; UNITED-STATES;
MELLITUS; DISEASE
AB Risk of weight change and fluctuation for type 2 diabetes was studied in a prospective study among 20,952 Finnish male smokers aged 50-69 years. Baseline data on lifestyle and medical history were collected, and height and weight measured. Weight was measured thrice after the baseline, 1 year apart. Weight change was defined as the slope of the regression line fitted to the four measurements and weight fluctuation as the root-mean-square-error deviation from this line. Incident cases of diabetes were identified from a national medication reimbursement register; 535 cases up to 9 years' follow-up. The Cox proportional hazards model served to estimate relative risk [RR, 95% confidence interval (CI)]. Weight gain and fluctuation associated with higher risk for diabetes, multivariate RR = 1.77, 95% CI 1.44-2.17, for weight gain of at least 4 kg compared with those of weight change less than 4 kg, and RR = 1.64, 95% CI 1.24-2.17 in the highest weight fluctuation quintile compared to the lowest. These RRs remained similar when weight change and fluctuation were adjusted for each other. Large weight fluctuation increased the risk of diabetes both in men who gained weight (a parts per thousand yen4 kg), had stable weight (+/- < 4 kg), and lost weight (a parts per thousand yen4 kg); RR = 2.17, 95% CI 1.60-2.94, RR = 1.47, 95% CI 1.14-1.91, and RR = 2.04, 95% CI 1.47-2.83, respectively, compared to those with stable weight and moderate fluctuation. Short-term weight gain and large weight fluctuation are independent risk factors for diabetes.
C1 [Kataja-Tuomola, Merja; Sundell, Jari; Mannisto, Satu; Virtanen, Mikko J.; Kontto, Jukka; Virtamo, Jarmo] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Helsinki 00271, Finland.
[Albanes, Demetrius] NCI, NIH, Bethesda, MD 20892 USA.
RP Kataja-Tuomola, M (reprint author), Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, PL 30, Helsinki 00271, Finland.
EM merja.kataja-tuomola@thl.fi
RI Albanes, Demetrius/B-9749-2015;
OI Mannisto, Satu/0000-0002-8668-3046; Kontto, Jukka/0000-0003-3899-9852
FU National Cancer Institute, NIH [N01-CN-45165, N01-RC-45035,
N01-RC-37004]; Department of Health and Human Services
FX This ATBC Study was supported by U.S. Public Health Service contracts
N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer
Institute, NIH, and the Department of Health and Human Services.
NR 48
TC 15
Z9 15
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
EI 1573-7284
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD MAY
PY 2010
VL 25
IS 5
BP 333
EP 339
DI 10.1007/s10654-010-9444-6
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 592WT
UT WOS:000277413200008
PM 20352298
ER
PT J
AU Marugan, JJ
Zheng, W
Motabar, O
Southall, N
Goldin, E
Sidransky, E
Aungst, RA
Liu, K
Sadhukhan, SK
Austin, CP
AF Marugan, Juan J.
Zheng, Wei
Motabar, Omid
Southall, Noel
Goldin, Ehud
Sidransky, Ellen
Aungst, Ronald A.
Liu, Ke
Sadhukhan, Subir Kumar
Austin, Christopher P.
TI Evaluation of
2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one
analogues as GAA activators
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Pompe disease; Lysosomal storage disorder; Acid alpha-glucosidase;
Activation of GM
ID ACID ALPHA-GLUCOSIDASE; GLYCOGENOSIS TYPE-II; DISEASE TYPE-II;
FIBROBLASTS; MUTATIONS
AB Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase. In several LSDs, enzyme inhibitors have been used as small molecule chaperones to facilitate and increase the translocation of mutant protein from the endoplasmic reticulum to the lysosome. Enzyme activators with chaperone activity would be even more desirable as they would not inhibit the enzyme after translocation and might potentiate the activity of the enzyme that is successfully translocated. Herein we report our initial findings of a new series of acid alpha-glucosidase activators. Published by Elsevier Masson SAS.
C1 [Marugan, Juan J.; Zheng, Wei; Motabar, Omid; Southall, Noel; Liu, Ke] NHGRI, NIH, Chem Genom Ctr, Rockville, MD USA.
[Motabar, Omid; Goldin, Ehud; Sidransky, Ellen; Austin, Christopher P.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Aungst, Ronald A.] Albany Mol Res Inc, Albany, NY 12203 USA.
[Sadhukhan, Subir Kumar] Albany Mol Res Hyderabad Res Ctr, Hyderabad 500078, Andhra Pradesh, India.
RP Marugan, JJ (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Rockville, MD USA.
EM maruganj@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU NIH Roadmap for Medical Research; National Human Genome Research
Institute; National Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health.
NR 23
TC 14
Z9 14
U1 0
U2 1
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD MAY
PY 2010
VL 45
IS 5
BP 1880
EP 1897
DI 10.1016/j.ejmech.2010.01.027
PG 18
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 583RA
UT WOS:000276695200024
PM 20206419
ER
PT J
AU Chen, YH
Edgar, JC
Holroyd, T
Dammers, J
Thonnessen, H
Roberts, TPL
Mathiak, K
AF Chen, Yu-Han
Edgar, J. Christopher
Holroyd, Tom
Dammers, Juergen
Thoennessen, Heike
Roberts, Timothy P. L.
Mathiak, Klaus
TI Neuromagnetic oscillations to emotional faces and prosody
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE emotion; MEG; multisensory integration; prosody; unisensory
ID SUPERIOR TEMPORAL SULCUS; HUMAN AUDITORY-CORTEX; EVENT-RELATED FMRI;
HUMAN BRAIN; MULTISENSORY INTERACTIONS; AUDIOVISUAL INTEGRATION; FACIAL
EXPRESSIONS; CROSSMODAL BINDING; BAND OSCILLATIONS; EEG ALPHA
AB Higher association cortices as well as unisensory areas can support multisensory integration [D. Senkowski et al. (2008) Trends Neurosci., 31, 401-409]. The present study investigated whether audiovisual integration of emotional information emerges early at unisensory or later at higher association cortices. Emotional stimuli were presented in three blocks: audiovisual (AV), auditory (A) and visual (V). Eighteen participants performed a delayed emotional recognition task (happy, angry or neutral prosody and/or facial expression) while whole-brain magnetoencephalography (MEG) data were obtained. Time-frequency evoked and total power analyses were performed on the sensor data, and source localization of the frequencies of interest performed via a synthetic aperture magnetometry beamformer. To examine crossmodal integration between bimodal and unimodal conditions, two contrasts were specified: AV > A and AV > V. In the AV > A contrast, early effects were observed on both the temporal and the occipital evoked responses. However, at the source level, early alpha suppression was limited to the occipital sources without changes in temporal cortices. In the AV > V contrast, sensor and source findings revealed increased alpha suppression only in temporal cortices, with no changes in visual cortex. Thus, no crossmodal effect in unisensory areas emerged. Instead, increased frontal alpha activity in both the AV > A and AV > V contrasts supports the view that affective information from face and prosody converges at higher association cortices.
C1 [Chen, Yu-Han; Thoennessen, Heike; Mathiak, Klaus] Rhein Westfal TH Aachen, JARA Brain, Dept Psychiat & Psychotherapy, D-52074 Aachen, Germany.
[Edgar, J. Christopher; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA USA.
[Holroyd, Tom] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Dammers, Juergen] Forschungszentrum Julich, Inst Neurosci & Med 4, D-52425 Julich, Germany.
[Mathiak, Klaus] Forschungszentrum Julich, Inst Neurosci & Med 1, D-52425 Julich, Germany.
RP Chen, YH (reprint author), Rhein Westfal TH Aachen, JARA Brain, Dept Psychiat & Psychotherapy, D-52074 Aachen, Germany.
EM yuhanmc@gmail.com
RI Dammers, Jurgen/I-1485-2013
OI Dammers, Jurgen/0000-0003-1526-6592
FU Deutsche Forschungsgemeinschaft (DFG) [IRTG 1328, MA 2631/4-1];
Pennsylvania Department of Health
FX This study was supported by Deutsche Forschungsgemeinschaft (DFG; IRTG
1328 and MA 2631/4-1) and in part by a grant from the Pennsylvania
Department of Health. The Pennsylvania Department of Health specifically
disclaims responsibility for any analyses, interpretations or
conclusions.
NR 48
TC 17
Z9 17
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAY
PY 2010
VL 31
IS 10
BP 1818
EP 1827
DI 10.1111/j.1460-9568.2010.07203.x
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 597TL
UT WOS:000277784500014
PM 20584186
ER
PT J
AU Hirvonen, J
Terry, GE
Halldin, C
Pike, VW
Innis, RB
AF Hirvonen, Jussi
Terry, Garth E.
Halldin, Christer
Pike, Victor W.
Innis, Robert B.
TI Approaches to quantify radioligands that wash out slowly from target
organs
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Editorial Material
ID POSITRON-EMISSION-TOMOGRAPHY; CANNABINOID CB1 RECEPTORS; BINDING; BRAIN;
PARAMETERS
C1 [Hirvonen, Jussi; Terry, Garth E.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 31 Ctr Dr,MSC-2035, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
FU Intramural NIH HHS [Z01 MH002852-04]; NIMH NIH HHS [Z01-MH-002852-04,
Z01 MH002852]
NR 10
TC 8
Z9 8
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD MAY
PY 2010
VL 37
IS 5
BP 917
EP 919
DI 10.1007/s00259-010-1426-0
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 583HN
UT WOS:000276664600009
PM 20358196
ER
PT J
AU Han, MK
Wise, R
Mumford, J
Sciurba, F
Criner, GJ
Curtis, JL
Murray, S
Sternberg, A
Weinman, G
Kazerooni, E
Fishman, AP
Make, B
Hoffman, EA
Mosenifar, Z
Martinez, FJ
AF Han, M. K.
Wise, R.
Mumford, J.
Sciurba, F.
Criner, G. J.
Curtis, J. L.
Murraye, S.
Sternberg, A.
Weinman, G.
Kazerooni, E.
Fishman, A. P.
Make, B.
Hoffman, E. A.
Mosenifar, Z.
Martinez, F. J.
CA NETT Res Grp
TI Prevalence and clinical correlates of bronchoreversibility in severe
emphysema
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
DE Bronchodilator; chronic obstructive pulmonary disease; computed
tomography; emphysema
ID OBSTRUCTIVE PULMONARY-DISEASE; VOLUME-REDUCTION SURGERY; AIR-FLOW
LIMITATION; BRONCHODILATOR RESPONSE; FLUTICASONE PROPIONATE; SALMETEROL
XINAFOATE; RANDOMIZED-TRIAL; LUNG HEALTH; COPD; HYPERINFLATION
AB Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial.
We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility.
544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography.
Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (>= 400 mL) changes in forced vital capacity (FVC).
In a severe emphysema population, bronchoreversibility as defined by change in FEV1 is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.
C1 [Han, M. K.] Univ Michigan, Med Ctr, Div Pulm & Crit Care Med, Taubman Ctr 3916,Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Murraye, S.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Kazerooni, E.] Univ Michigan, Sch Publ Hlth, Dept Radiol, Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA.
[Wise, R.; Sternberg, A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Wise, R.; Sternberg, A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Weinman, G.] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA.
[Mosenifar, Z.] Cedars Sinai Med Ctr, Div Pulm Med, Los Angeles, CA 90048 USA.
[Sciurba, F.] Univ Pittsburgh, Div Pulm & Crit Care Med, Pittsburgh, PA USA.
[Criner, G. J.] Temple Univ, Philadelphia, PA 19122 USA.
[Fishman, A. P.] Univ Penn, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA.
[Make, B.] Natl Jewish Hlth, Div Pulm Sci, Denver, CO USA.
[Hoffman, E. A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
RP Han, MK (reprint author), Univ Michigan, Med Ctr, Div Pulm & Crit Care Med, Taubman Ctr 3916,Sch Publ Hlth, Box 0360,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM mrking@umich.edu
RI Reilly, John/H-8755-2012;
OI Wise, Robert/0000-0002-8353-2349; Murray, Susan/0000-0003-4387-7673;
Curtis, Jeffrey/0000-0001-5191-4847
FU National Heart, Lung, and Blood Institute [N01HR76101, N01HR76102,
N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108,
N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114,
N01HR76115, N01HR76116, N01HR76118, N01HR76119]
FX The National Emphysema Treatment Trial (NETT) was supported by contracts
with the National Heart, Lung, and Blood Institute (N01HR76101,
N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107,
N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113,
N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119;
Bethesda, MD, USA), the Centers for Medicare and Medicaid Services
(Baltimore, MD, USA; formerly the Health Care Financing Administration)
and the Agency for Healthcare Research and Quality. This research was
further supported by National Institutes of Health grants K24 HL04212,
K23 HL68713, and RO-1 HL56309; by a General Electric Radiology Research
Academic Fellowship; by a grant fromGeneral Electric Medical Systems, CT
Division (Waukesha, WI, USA); and by Merit Review and a Research
Enhancement Award Program funding from the Department of Veterans
Affairs (Washington, DC, USA). J. L. Curtis is supported by funding from
a Research Enhancement Award Program (REAP) from the Biomedical
Laboratory Research and Development Service, Department of Veterans
Affairs.
NR 43
TC 20
Z9 20
U1 0
U2 4
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD MAY
PY 2010
VL 35
IS 5
BP 1048
EP 1056
DI 10.1183/09031936.00052509
PG 9
WC Respiratory System
SC Respiratory System
GA 591WB
UT WOS:000277334800015
PM 19926748
ER
PT J
AU Percopo, CM
Dyer, KD
Killoran, KE
Rosenberg, HF
AF Percopo, Caroline M.
Dyer, Kimberly D.
Killoran, Kristin E.
Rosenberg, Helene F.
TI Isolation of human eosinophils: microbead method has no impact on IL-5
sustained viability
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Letter
DE apoptosis; CD16; eosinophil; interleukin-5; microbeads
AB P>Background/purpose:
In a recent issue of Experimental Dermatology (18, 2009, 654), Schefzyk et al. concluded that multi-antibody eosinophil isolation (Miltenyi) should be abandoned, as differential purity was minimal, and eosinophils underwent accelerated apoptosis when compared with those isolated with traditional anti-CD16 microbeads. Our intent was to investigate the universality of these findings.
Methods:
We isolated eosinophils from normal donor granulocyte packs using two methods, and evaluated purity, viability and annexin-V/propidium-iodide staining.
Results:
Purity was substantially greater when multi-antibody isolation was used for eosinophil isolation from granulocyte packs (98% vs 69%). No differential survival was detected when eosinophils were maintained in culture with or without interleukin-5.
Conclusions:
Multi-antibody eosinophil isolation represents a substantial advantage over anti-CD-16 microbeads when isolating large numbers of eosinophils from concentrated leucocyte preparations. No differential survival was observed. While appropriate consideration of methods is always crucial, multi-antibody eosinophil isolation should not be abandoned completely.
C1 [Killoran, Kristin E.] NIAID, Lymphocyte Biol Unit, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Percopo, Caroline M.; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIAID, Lymphocyte Biol Unit, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,MSC1883, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000943-04, Z01 AI000941-04, Z99 AI999999]
NR 7
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAY
PY 2010
VL 19
IS 5
BP 467
EP 469
DI 10.1111/j.1600-0625.2009.00974.x
PG 3
WC Dermatology
SC Dermatology
GA 582NK
UT WOS:000276604500011
PM 19758339
ER
PT J
AU Wang, RXE
Taubenberger, JK
AF Wang, Ruixue
Taubenberger, Jeffery K.
TI Methods for molecular surveillance of influenza
SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
LA English
DT Review
DE influenza A virus; molecular surveillance; real-time PCR; RT-PCR;
surveillance
ID A H1N1 VIRUS; MEDIATED ISOTHERMAL AMPLIFICATION;
REVERSE-TRANSCRIPTION-PCR; H5N1 AVIAN INFLUENZA; TIME RT-PCR; POLYMERASE
CHAIN-REACTION; UNIVERSAL PRIMER SET; PANDEMIC INFLUENZA; UNITED-STATES;
WILD BIRDS
AB Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The recent pandemic of the swine-origin influenza A virus (H1N1) and the continuing circulation of highly pathogenic avian influenza A virus (H5N1) further stress the need for rapid and accurate identification and subtyping of influenza viruses for surveillance, outbreak management, diagnosis and treatment. There has been remarkable progress on the detection and molecular characterization of influenza virus infections in clinical, mammalian, domestic poultry and wild bird samples in recent years. The application of these techniques, including reverse transcriptase-PCR, real-time PCR, microarrays and other nucleic acid sequencing-based amplifications, have greatly enhanced the capability for surveillance and characterization of influenza viruses.
C1 [Wang, Ruixue; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
FU NIAID; NIH
FX This research was supported by the Intramural Research Program of the
NIAID and the NIH. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 106
TC 36
Z9 40
U1 0
U2 6
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-7210
J9 EXPERT REV ANTI-INFE
JI Expert Rev. Anti-Infect. Ther.
PD MAY
PY 2010
VL 8
IS 5
BP 517
EP 527
DI 10.1586/ERI.10.24
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 604LR
UT WOS:000278281000012
PM 20455681
ER
PT J
AU Boyd, AS
Fairchild, PJ
AF Boyd, Ashleigh S.
Fairchild, Paul J.
TI Approaches for immunological tolerance induction to stem cell-derived
cell replacement therapies
SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY
LA English
DT Review
DE cell replacement therapy; embryonic stem cells; immunogenicity; induced
pluripotent stem cells; regulatory T cells; stem cells; tolerance;
transplantation
ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; VERSUS-HOST-DISEASE; DENDRITIC CELLS; IN-VITRO;
TGF-BETA; IMMUNE PRIVILEGE; RETINOIC-ACID; DIRECTED DIFFERENTIATION
AB The shortage of donors for organ transplantation and also to treat degenerative diseases has led to the development of the new field of regenerative medicine. One aim of this field, in addition to in vivo induction of endogenous tissue regeneration, is to utilize stem cells as a supplementary source of cells to repair or replace tissues or organs that have ceased to function owing to ageing or autoimmunity. Embryonic stem cells hold promise in this respect because of their developmental capacity to generate all tissues within the body. More recently, the discovery of induced pluripotent stem cells, somatic cells reprogrammed to a primitive embryonic-like state by the introduction of pluripotency factors, may also act as an important cell source for cell replacement therapy. However, before cell replacement therapy can become a reality, one must consider how to overcome the potential transplant rejection of stem cell-derived products. There are several potential ways to circumvent the hurdles presented by the immune system in this setting, not least the induction of immunological tolerance in the host. In this review, we consider this and other approaches for engendering acceptance of stem cell-derived tissues.
C1 [Boyd, Ashleigh S.; Fairchild, Paul J.] Univ Oxford, Sir William Dunn Sch Pathol, Stem Cell Sci Lab, Oxford OX1 3RE, England.
RP Boyd, AS (reprint author), Boston Univ, Sch Med, Roger Williams Hosp, NIH Ctr Biomed Res Excellence Tissue Repair & Ste, Prior 214,825 Chalkstone Ave, Providence, RI 02908 USA.
EM aboyd@rwmc.org
FU Geron Corporation (Menlo Park, CA, USA); Medical Research Council UK;
Oxford Stem Cell Institute at the James Martin 21st Century School
(Oxford, UK); NIH [P20RR018757]
FX Work in the authors' laboratory was supported by Geron Corporation
(Menlo Park, CA, USA), the Medical Research Council UK and the Oxford
Stem Cell Institute at the James Martin 21st Century School (Oxford,
UK). Further support to Ashleigh S Boyd was provided by NIH grant
P20RR018757 and its administrative core. 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 178
TC 13
Z9 17
U1 0
U2 2
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1744-666X
J9 EXPERT REV CLIN IMMU
JI Expert Rev. Clin. Immunol.
PD MAY
PY 2010
VL 6
IS 3
BP 435
EP 448
DI 10.1586/ECI.10.20
PG 14
WC Immunology
SC Immunology
GA 602VI
UT WOS:000278166600018
PM 20441429
ER
PT J
AU Balakumaran, A
Robey, PG
Fedarko, N
Landgren, O
AF Balakumaran, Arun
Robey, Pamela Gehron
Fedarko, Neal
Landgren, Ola
TI Bone marrow microenvironment in myelomagenesis: its potential role in
early diagnosis
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
DE angiogenesis; bone marrow microenvironment; bone turnover; extracellular
matrix; monoclonal gammopathy of unknown significance; multiple myeloma;
multiplex ELISA; osteoclast; proteoglycans; RANK ligand; Wnt signaling
ID HUMAN MULTIPLE-MYELOMA; ENDOTHELIAL GROWTH-FACTOR; PLASMA-CELL
DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; MESENCHYMAL STEM-CELLS;
INHIBITS TUMOR-GROWTH; RESISTANCE CAM-DR; TISSUE INHIBITOR; MONOCLONAL
GAMMOPATHY; DENDRITIC CELLS
AB Multiple myeloma (MM) is the second most common hematological malignancy, with an overall survival of 4-6 years. It is always preceded by a premalignant stage called monoclonal gammopathy of unknown significance (MGUS). Importantly, at this time we lack reliable predictors to determine who will progress from MGUS to MM, and who will remain stable. The bone marrow microenvironment plays a key role in myelomagenesis (growth, survival and migration of malignant plasma cells). In the present review, we summarize and discuss our current understanding of the bone marrow microenvironment and its compartments in relation to myelomagenesis. Although it remains to be proven, we believe that an improved characterization of the cellular constituents, the extracellular matrix components and the soluble factors of the bone marrow could open up novel avenues to better understand underlying mechanisms of the transformation from MGUS to MM. Ultimately, this will lead to the development of early treatment of high-risk precursor disease aimed to delay/prevent MM.
C1 [Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
[Balakumaran, Arun; Robey, Pamela Gehron] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Fedarko, Neal] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA.
RP Landgren, O (reprint author), NCI, NIH, Bldg 10,Room 13N240,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; Fedarko, Neal/0000-0001-6055-6279
FU Intramural NIH HHS [Z01 DE000380-25]
NR 135
TC 24
Z9 25
U1 1
U2 4
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7159
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD MAY
PY 2010
VL 10
IS 4
BP 465
EP 480
DI 10.1586/ERM.10.31
PG 16
WC Pathology
SC Pathology
GA 601FB
UT WOS:000278042600010
PM 20465501
ER
PT J
AU Wu, DM
Khanna, H
Atmaca-Sonmez, P
Sieving, PA
Branham, K
Othman, M
Swaroop, A
Daiger, SP
Heckenlively, JR
AF Wu, D. M.
Khanna, H.
Atmaca-Sonmez, P.
Sieving, P. A.
Branham, K.
Othman, M.
Swaroop, A.
Daiger, S. P.
Heckenlively, J. R.
TI Long-term follow-up of a family with dominant X-linked retinitis
pigmentosa
SO EYE
LA English
DT Article
DE X-linked dominant retinitis pigmentosa; RPGR; ORF15
ID CONE-ROD DEGENERATION; RPGR EXON ORF15; VISUAL FUNCTION; MUTATIONS;
GENE; CARRIERS; RP2; IDENTIFICATION; CHROMOSOME; PHENOTYPE
AB Purpose To document the progression of disease in male and female members of a previously described family with X-linked dominant retinitis pigmentosa (RP) caused by a de novo insertion after nucleotide 173 in exon ORF15 of RPGR.
Methods The clinical records of 19 members of family UTAD054 were reviewed. Their evaluations consisted of confirmation of family history, standardised electroretinograms (ERGs), Goldmann visual fields, and periodic ophthalmological examinations over a 23-year period.
Results Male members of family UTAD054 had non-recordable to barely recordable ERGs from early childhood. The males showed contracted central fields and developed more severe retinopathy than the females. The female members showed a disease onset delayed to teenage years, recordable but diminishing photopic and scotopic ERG amplitudes in a cone-rod pattern, progressive loss and often asymmetric visual fields, and diffuse atrophic retinopathy with fewer pigment deposits compared with males.
Conclusions This insertion mutation in the RPGR exon ORF15 is associated with a RP phenotype that severely affects males early and females by 30 years of age, and is highly penetrant in female members. Families with dominant-acting RPGR mutations may be mistaken to have an autosomal mode of inheritance resulting in an incorrect prediction of recurrence risk and prognosis. Broader recognition of X-linked RP forms with dominant inheritance is necessary to facilitate appropriate counselling of these patients. Eye (2010) 24, 764-774; doi:10.1038/eye.2009.270; published online 6 November 2009
C1 [Wu, D. M.; Khanna, H.; Atmaca-Sonmez, P.; Branham, K.; Othman, M.; Swaroop, A.; Heckenlively, J. R.] Univ Michigan, Dept Ophthalmol & Visual Sci, WK Kellogg Eye Ctr, Ann Arbor, MI 48105 USA.
[Sieving, P. A.] NEI, Bethesda, MD 20892 USA.
[Swaroop, A.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA.
[Daiger, S. P.] Univ Texas Houston Hlth Sci Ctr, Dept Human Genet, Houston, TX USA.
RP Heckenlively, JR (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, WK Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM jrheck@umich.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU Foundation for Fighting Blindness; NIH [EY007961]
FX This study was funded by the Foundation for Fighting Blindness; NIH
EY007961. We thank James Friedman, Naheed Khan and Randall Wallach for
their helpful discussion in the preparation of this article.
NR 36
TC 13
Z9 13
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD MAY
PY 2010
VL 24
IS 5
BP 764
EP 774
DI 10.1038/eye.2009.270
PG 11
WC Ophthalmology
SC Ophthalmology
GA 595EG
UT WOS:000277592900003
PM 19893586
ER
PT J
AU Cukras, C
Wang, YD
Meyerle, CB
Forooghian, F
Chew, EY
Wong, WT
AF Cukras, C.
Wang, Y. D.
Meyerle, C. B.
Forooghian, F.
Chew, E. Y.
Wong, W. T.
TI Optical coherence tomography-based decision making in exudative
age-related macular degeneration: comparison of time- vs spectral-domain
devices
SO EYE
LA English
DT Article
DE age-related macular degeneration; optical coherence tomography; clinical
trials; neovascularization; anti-angiogenic treatment
ID RETINAL THICKNESS MEASUREMENTS; BEVACIZUMAB AVASTIN THERAPY;
REPRODUCIBILITY; REPEATABILITY; RANIBIZUMAB; AGREEMENT
AB Purpose To determine whether optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD).
Methods Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus OCT system and the spectral-domain Cirrus OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analysed.
Results Cirrus OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients for all parameters analysed. A pair-wise comparison of Cirrus OCT with Stratus OCT systems revealed that Cirrus-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (P<0.05) compared with Stratus-based gradings.
Conclusions The choice of time-domain (Stratus) vs spectra-domain (Cirrus) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials using OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis. Eye (2010) 24, 775-783; doi:10.1038/eye.2009.211; published online 21 August 2009
C1 [Wang, Y. D.; Wong, W. T.] NEI, Unit Neuron Glia Interact, NIH, Bethesda, MD 20892 USA.
[Cukras, C.; Meyerle, C. B.; Forooghian, F.; Chew, E. Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact, NIH, 6 Ctr Dr,Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute
FX This work has been supported by the National Eye Institute Intramural
Research Program.
NR 16
TC 25
Z9 25
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
J9 EYE
JI Eye
PD MAY
PY 2010
VL 24
IS 5
BP 775
EP 783
DI 10.1038/eye.2009.211
PG 9
WC Ophthalmology
SC Ophthalmology
GA 595EG
UT WOS:000277592900004
PM 19696804
ER
PT J
AU Kajava, AV
Baxa, U
Steven, AC
AF Kajava, Andrey V.
Baxa, Ulrich
Steven, Alasdair C.
TI beta arcades: recurring motifs in naturally occurring and
disease-related amyloid fibrils
SO FASEB JOURNAL
LA English
DT Review
DE amyloidogenicity; polymorphism; prion; misfolding; structural motif
ID SOLID-STATE NMR; PAIRED HELICAL FILAMENTS; URE2P PRION FILAMENTS;
PROTEIN AGGREGATION; STRUCTURAL MODELS; EXPERIMENTAL CONSTRAINTS;
SOLENOID PROTEINS; SHEET STRUCTURE; 3D STRUCTURE; IN-VITRO
AB Amyloid fibrils are filamentous protein aggregates that accumulate in diseases such as Alzheimer's or type II diabetes. The amyloid-forming protein is disease specific. Amyloids may also be formed in vitro from many other proteins, after first denaturing them. Unlike the diverse native folds of these proteins, their amyloids are fundamentally similar in being rigid, smooth-sided, and cross-beta-structured, that is, with beta strands running perpendicular to the fibril axis. In the absence of high-resolution fibril structures, increasingly credible models are being derived by integrating data from a crossfire of experimental techniques. Most current models of disease-related amyloids invoke "beta arcades," columnar structures produced by in-register stacking of "beta arches." A beta arch is a strand-turn-strand motif in which the two beta strands interact via their side chains, not via the polypeptide backbone as in a conventional beta hairpin. Crystal structures of beta-solenoids, a class of proteins with amyloid-like properties, offer insight into the beta-arc turns found in beta arches. General conformational and thermodynamic considerations suggest that complexes of 2 or more beta arches may nucleate amyloid fibrillogenesis in vivo. The apparent prevalence of beta arches and their components have implications for identifying amyloidogenic sequences, elucidating fibril polymorphisms, predicting the locations and conformations of beta arcs within amyloid fibrils, and refining existing fibril models.-Kajava, A. V., Baxa, U., Steven, A. C. beta arcades: recurring motifs in naturally occurring and disease-related amyloid fibrils. FASEB J. 24, 1311-1319 (2010). www.fasebj.org
C1 [Baxa, Ulrich; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kajava, Andrey V.] Univ Montpellier 1, CNRS, Ctr Rech Biochim & Macromol, Montpellier, France.
[Kajava, Andrey V.] Univ Montpellier 2, CNRS, Ctr Rech Biochim & Macromol, Montpellier, France.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 50,Room 1517,MSC 8025, Bethesda, MD 20892 USA.
EM andrey.kajava@crbm.cnrs.fr; stevena@mail.nih.gov
RI Kajava, Andrey/E-1107-2014
OI Kajava, Andrey/0000-0002-2342-6886
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases at
the National Institutes of Health, Bethesda, MD, USA
FX The authors thank Drs. Oleg Borisov and Christian Ligoure for discussion
and suggestions. This work was supported in part by the Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases at the National Institutes of Health,
Bethesda, MD, USA.
NR 70
TC 56
Z9 57
U1 1
U2 22
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 MAY
PY 2010
VL 24
IS 5
BP 1311
EP 1319
DI 10.1096/fj.09-145979
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 589OD
UT WOS:000277158900004
PM 20032312
ER
PT J
AU Wang, FE
Zhang, CN
Maminishkis, A
Dong, LJ
Zhi, CN
Li, R
Zhao, J
Majerciak, V
Gaur, AB
Chen, S
Miller, SS
AF Wang, Fei E.
Zhang, Connie
Maminishkis, Arvydas
Dong, Lijin
Zhi, Connie
Li, Rong
Zhao, Jing
Majerciak, Vladimir
Gaur, Arti B.
Chen, Shan
Miller, Sheldon S.
TI MicroRNA-204/211 alters epithelial physiology
SO FASEB JOURNAL
LA English
DT Article
DE tumorigenesis; transepithelial resistance; membrane potential; tight
junctions; claudins; retinal pigment epithelium
ID RETINAL-PIGMENT EPITHELIUM; CENTRAL-NERVOUS-SYSTEM; FACTOR-H
POLYMORPHISM; MACULAR DEGENERATION; FLUID TRANSPORT; MESENCHYMAL
TRANSITION; GENE-EXPRESSION; MIR-200 FAMILY; CANCER-CELLS; MICRORNAS
AB MicroRNA (miRNA) expression in fetal human retinal pigment epithelium (hfRPE), retina, and choroid were pairwise compared to determine those miRNAs that are enriched by 10-fold or more in each tissue compared with both of its neighbors. miRs-184, 187, 200a/200b, 204/211, and 221/222 are enriched in hfRPE by 10- to 754-fold compared with neuroretina or choroid (P<0.05). Five of these miRNAs are enriched in RPE compared with 20 tissues throughout the body and are 10- to 20,000-fold more highly expressed (P<0.005). miR-204 and 211 are the most highly expressed in the RPE. In addition, expression of miR-204/211 is significantly lower in the NCI60 tumor cell line panel compared with that in 13 normal tissues, suggesting the progressive disruption of epithelial barriers and increased proliferation. We demonstrated that TGF-beta receptor 2 (TGF-beta R2) and SNAIL2 are direct targets of miR-204 and that a reduction in miR-204 expression leads to reduced expression of claudins 10, 16, and 19 (message/protein) consistent with our observation that anti-miR-204/211 decreased transepithelial resistance by 80% and reduced cell membrane voltage and conductance. The anti-miR-204-induced decrease in Kir7.1 protein levels suggests a signaling pathway that connects TGF-beta R2 and maintenance of potassium homeostasis. Overall, these data indicate a critical role for miR-204/211 in maintaining epithelial barrier function and cell physiology.-Wang, F. E., Zhang, C., Maminishkis, A., Dong, L., Zhi, C., Li, R., Zhao, J., Majerciak, V., Gaur, A. B., Chen, S., Miller, S. S. MicroRNA-204/211 alters epithelial physiology. FASEB J. 24, 1552-1571 (2010). www.fasebj.org
C1 [Miller, Sheldon S.] NEI, NIH, Bethesda, MD 20892 USA.
[Majerciak, Vladimir] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Gaur, Arti B.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH USA.
RP Miller, SS (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA.
EM millers@nei.nih.gov
FU Intramural NIH HHS [Z01 EY000421-04]
NR 73
TC 117
Z9 126
U1 0
U2 10
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD MAY
PY 2010
VL 24
IS 5
BP 1552
EP 1571
DI 10.1096/fj.08-125856
PG 20
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 589OD
UT WOS:000277158900028
PM 20056717
ER
PT J
AU Hoashi, T
Sato, S
Yamaguchi, Y
Passeron, T
Tamaki, K
Hearing, VJ
AF Hoashi, Toshihiko
Sato, Shinichi
Yamaguchi, Yuji
Passeron, Thierry
Tamaki, Kunihiko
Hearing, Vincent J.
TI Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell
marker, is a melanosome-specific and proteolytically released protein
SO FASEB JOURNAL
LA English
DT Article
DE ectodomain shedding; glycosylation; phorbol ester
ID MALIGNANT-MELANOMA; DESMOPLASTIC MELANOMA; PRECURSOR PROTEIN; REPEAT
DOMAIN; EXPRESSION; PMEL17; CLEAVAGE; OSTEOACTIVIN; ECTODOMAIN; MEMBRANE
AB Melanosomes are organelles specialized for the production of melanin pigment and are specifically produced by melanocytic cells. More than 150 pigmentation-related genes have been identified, including glycoprotein nonmetastatic melanoma protein b (GPNMB). A recent proteomics analysis revealed that GPNMB is localized in melanosomes, and GPNMB is a membrane-bound glycoprotein that shows high homology with a well-known melanosomal structural protein, Pmel17/gp100. In this study, we show that GPNMB is expressed in melanocytes of normal human skin, as well as in human melanoma cells. GPNMB is heavily glycosylated and is enriched in mature (stage III and IV) melanosomes in contrast to MART-1 and Pmel17, which are abundant in early (stage I and II) melanosomes. MART-1 and Pmel17 play critical roles in the maturation of early melanosomes; thus, we speculate that GPNMB might be important in the functions of late melanosomes, possibly their transport and/or transfer to keratinocytes. We also demonstrate that a secreted form of GPNMB is released by ectodomain shedding from the largely Golgi-modified form of GPNMB and that the PKC and Ca(2+) intracellular signaling pathways regulate that shedding. We conclude that GPNMB is a melanosomal protein that is released by proteolytic ectodomain shedding and might be a useful and specific histological marker of melanocytic cells.-Hoashi, T., Sato, S., Yamaguchi, Y., Passeron, T., Tamaki, K., Hearing, V. J. Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. FASEB J. 24, 1616-1629 (2010). www.fasebj.org
C1 [Hoashi, Toshihiko; Yamaguchi, Yuji; Passeron, Thierry; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Hoashi, Toshihiko; Sato, Shinichi; Tamaki, Kunihiko] Univ Tokyo, Fac Med, Dept Dermatol, Tokyo 113, Japan.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA.
EM thoashi-tky@umin.ac.jp; hearingv@nih.gov
OI Passeron, Thierry/0000-0002-0797-6570
FU Shiseido grant for science research; U.S. National Institutes of Health,
National Cancer Institute
FX The authors gratefully thank Dr. Michael S. Marks (University of
Pennsylvania, Philadelphia, PA, USA) for kindly providing the Pmel17-i
vector. This work was largely supported by a Shiseido grant for science
research (T.H.) and in part by the Intramural Research Program of the
U.S. National Institutes of Health, National Cancer Institute.
NR 74
TC 44
Z9 50
U1 0
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 MAY
PY 2010
VL 24
IS 5
BP 1616
EP 1629
DI 10.1096/fj.09-151019
PG 14
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 589OD
UT WOS:000277158900033
PM 20056711
ER
PT J
AU Notari, L
Arakaki, N
Mueller, D
Meier, S
Amaral, J
Becerra, SP
AF Notari, Luigi
Arakaki, Naokatu
Mueller, David
Meier, Scott
Amaral, Juan
Becerra, S. P.
TI Pigment epithelium-derived factor binds to cell-surface F-1-ATP synthase
SO FEBS JOURNAL
LA English
DT Article
DE endothelial cells; F1-ATPase; F1Fo-ATP synthase; PEDF; surface plasmon
resonance
ID MEDIATED GENE-TRANSFER; ATP SYNTHASE; FACTOR PEDF; CHOROIDAL
NEOVASCULARIZATION; ENDOTHELIAL-CELLS; TUMOR-GROWTH; BOVINE EYES;
ANGIOSTATIN; ANGIOGENESIS; IDENTIFICATION
AB Pigment epithelium-derived factor (PEDF), a potent blocker of angiogenesis in vivo, and of endothelial cell migration and tubule formation, binds with high affinity to an as yet unknown protein on the surfaces of endothelial cells. Given that protein fingerprinting suggested a match of a similar to 60 kDa PEDF-binding protein in bovine retina with Bos taurus F-1-ATP synthase beta-subunit, and that F1Fo-ATP synthase components have been identified recently as cell-surface receptors, we examined the direct binding of PEDF to F-1. Size-exclusion ultrafiltration assays showed that recombinant human PEDF formed a complex with recombinant yeast F-1. Real-time binding as determined by surface plasmon resonance demonstrated that yeast F-1 interacted specifically and reversibly with human PEDF. Kinetic evaluations revealed high binding affinity for PEDF, in agreement with PEDF affinities for endothelial cell surfaces. PEDF blocked interactions between F-1 and angiostatin, another antiangiogenic factor, suggesting overlapping PEDF-binding and angiostatin-binding sites on F-1. Surfaces of endothelial cells exhibited affinity for PEDF-binding proteins of similar to 60 kDa. Antibodies to F-1 beta-subunit specifically captured PEDF-binding components in endothelial plasma membranes. The extracellular ATP synthesis activity of endothelial cells was examined in the presence of PEDF. PEDF significantly reduced the amount of extracellular ATP produced by endothelial cells, in agreement with direct interactions between cell-surface ATP synthase and PEDF. In addition to demonstrating that PEDF binds to cell-surface F-1, these results show that PEDF is a ligand for endothelial cell-surface F1Fo-ATP synthase. They suggest that PEDF-mediated inhibition of ATP synthase may form part of the biochemical mechanisms by which PEDF exerts its antiangiogenic activity.
C1 [Notari, Luigi; Arakaki, Naokatu; Amaral, Juan; Becerra, S. P.] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Arakaki, Naokatu] Univ Tokushima, Grad Sch, Tokushima, Japan.
[Mueller, David; Meier, Scott] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Biochem & Mol Biol, Chicago, IL USA.
RP Becerra, SP (reprint author), NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, NIH, Bldg 6,Room 134,6 Ctr Dr, Bethesda, MD 20892 USA.
EM becerrap@nei.nih.gov
FU NIH, NEI; NIH [R01-GM066223]
FX This research was supported in part by the Intramural Research Program
of the NIH, NEI, and NIH Grant R01-GM066223. We thank T. Higuti for
starting the collaboration between N. Arakaki and our group, P. Schuck
for interesting discussions on SPR kinetic evaluations and confirming
SPR evaluations with our data, and I. Rodriguez and V. Notario for
critically reading the manuscript.
NR 42
TC 30
Z9 31
U1 2
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD MAY
PY 2010
VL 277
IS 9
BP 2192
EP 2205
DI 10.1111/j.1742-4658.2010.07641.x
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 585UV
UT WOS:000276855900018
PM 20412062
ER
PT J
AU Tulandi, T
Shehata, FF
DeCherney, A
AF Tulandi, Togas
Shehata, Fady F.
DeCherney, Alan
TI Fertility and Sterility and impact factor
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Impact factor; citation; Fertility and Sterility; Scopus; Thompson
AB Increasing the number of articles and reviews does not lead to an increased impact factor. The type and quality of the articles might influence this result. Compared with the traditional 2-year impact factor, a 5-year impact factor fluctuates little, and may be a better indicator for evaluation of published journals. (Fertil Steril (R) 2010;93:2105-6. (C)2010 by American Society for Reproductive Medicine.)
C1 [Tulandi, Togas; Shehata, Fady F.] McGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 1A1, Canada.
[DeCherney, Alan] NICHD, NIH, Bethesda, MD USA.
RP Shehata, FF (reprint author), McGill Univ, Dept Obstet & Gynecol, 687 Pine Ave W, Montreal, PQ H3A 1A1, Canada.
EM fady.shehata@mail.mcgill.ca
RI Shehata, Fady/C-1401-2008;
OI Shehata, Fady/0000-0002-3741-9361
NR 3
TC 2
Z9 2
U1 0
U2 1
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 MAY 1
PY 2010
VL 93
IS 7
BP 2105
EP 2106
DI 10.1016/j.fertnstert.2010.01.065
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 595KD
UT WOS:000277608200002
PM 20226446
ER
PT J
AU Stanford, JB
Mikolajczyk, RT
Lynch, CD
Simonsen, SE
AF Stanford, Joseph B.
Mikolajczyk, Rafael T.
Lynch, Courtney D.
Simonsen, Sara E.
TI Cumulative pregnancy probabilities among couples with subfertility:
effects of varying treatments
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 21st Annual Meeting of the
Society-for-Pediatric-and-Perinatal-Epidemiology-Research
CY JUN 23-24, 2008
CL Chicago, IL
SP Soc Pediat & Perinatal Epidemiol Res
DE Infertility; statistical models; fertility; fertility agents; in vitro
fertilization
ID IN-VITRO FERTILIZATION; ASSISTED-REPRODUCTIVE-TECHNOLOGY;
FOLLICLE-STIMULATING-HORMONE; INTRAUTERINE INSEMINATION; ONGOING
PREGNANCY; UNEXPLAINED INFERTILITY; COST-EFFECTIVENESS; FERTILE WINDOW;
MUCUS OBSERVATIONS; SPERM INJECTION
AB Objective: To model the cumulative probability of pregnancy among couples with subfertility without a definitive diagnosis, according to different treatment strategies.
Design: A beta distribution of fecundity was fitted that reproduced the cumulative probability of pregnancy in prospective studies of natural fertility, and this distribution was applied to simulated cohorts starting with one million couples each. Probabilities of pregnancy were generated for each cycle of each couple.
Setting: Simulation study.
Patient(s): Hypothetic subfertile population.
Intervention(s): After 2 or 4 years of attempting pregnancy and diagnostic evaluation to exclude anovulation, tubal obstruction, and severe male factor, simulated treatments were applied to the remaining nonpregnant couples, with treatment effects based on published literature.
Main Outcome Measure(s): Simulated cumulative probability of pregnancy.
Result(s): Initially, the cumulative probability of pregnancy was highest for early treatment with IVF, but over time, conservative treatment or frequent intercourse approached the same cumulative probability.
Conclusion(s): In couples without clear indications for IVF, the main benefit of early IVF may be to shorten time to pregnancy, a benefit that must be weighed against costs and potential adverse outcomes. Couples should be encouraged to maintain regular intercourse to maximize chances of pregnancy, even after unsuccessful treatment attempts. (Fertil Steril (R) 2010;93:2175-81. (C)2010 by American Society for Reproductive Medicine.)
C1 [Mikolajczyk, Rafael T.] Univ Bielefeld, Dept Publ Hlth Med, Sch Publ Hlth, D-33501 Bielefeld, Germany.
[Lynch, Courtney D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Stanford, Joseph B.; Simonsen, Sara E.] Univ Utah, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT USA.
[Mikolajczyk, Rafael T.; Lynch, Courtney D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
RP Mikolajczyk, RT (reprint author), Univ Bielefeld, Dept Publ Hlth Med, Sch Publ Hlth, POB 100131, D-33501 Bielefeld, Germany.
EM rmikolajczyk@uni-bielefeld.de
OI Mikolajczyk, Rafael/0000-0003-1271-7204
FU Intramural NIH HHS
NR 63
TC 12
Z9 12
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 MAY 1
PY 2010
VL 93
IS 7
BP 2175
EP 2181
DI 10.1016/j.fertnstert.2009.01.080
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 595KD
UT WOS:000277608200013
PM 19328479
ER
PT J
AU Davis, M
Ventura, JL
Wieners, M
Covington, SN
Vanderhoof, VH
Ryan, ME
Koziol, DE
Popat, VB
Nelson, LM
AF Davis, Mary
Ventura, June L.
Wieners, Mary
Covington, Sharon N.
Vanderhoof, Vien H.
Ryan, Mary E.
Koziol, Deloris E.
Popat, Vaishali B.
Nelson, Lawrence M.
TI The psychosocial transition associated with spontaneous 46,XX primary
ovarian insufficiency: illness uncertainty, stigma, goal flexibility,
and purpose in life as factors in emotional health
SO FERTILITY AND STERILITY
LA English
DT Article
DE Primary ovarian insufficiency; hypergonadotropic hypogonadism; premature
ovarian failure; premature menopause; infertility; illness uncertainty;
stigma; goal flexibility
ID UNDERLYING COPING FLEXIBILITY; BAD-NEWS; PSYCHOLOGICAL DISTRESS;
COMPLICATED GRIEF; PERCEIVED STIGMA; CONTROLLED-TRIAL; MENTAL-ILLNESS;
BREAST-CANCER; YOUNG-WOMEN; FAILURE
AB Objective: To examine factors associated with emotional well-being in women with spontaneous primary ovarian insufficiency.
Design: Cross-sectional and case-control study.
Setting: Clinical research center, national U.S. health research facility.
Patient(s): Women diagnosed with spontaneous 46,XX primary ovarian insufficiency (n = 100) at a mean age of 32.4 years and healthy control women of similar age (n = 60).
Intervention(s): Administration of validated self-reporting instruments.
Main Outcome Measure(s): Illness uncertainty, stigma, goal disengagement/re-engagement, purpose in life, Positive and Negative Affect Schedule, Center of Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory.
Result(s): Compared with controls, women with spontaneous primary ovarian insufficiency scored adversely on all measures of affect. Illness uncertainty and purpose in life were significant independent factors associated with anxiety (R-2 = 0.47), stigma and purpose in life were the significant independent factors associated with depression (R-2 = 0.51), and goal re-engagement and purpose in life were significantly and independently associated with positive affect (R-2 = 0.43).
Conclusion(s): This evidence supports the need for prospective studies. Our findings are consistent with the hypothesis that clinicians could improve the emotional well-being of their patients with primary ovarian insufficiency by [1] informing them better about their condition, [2] helping them to feel less stigmatized by the disorder, and [3] assisting them in developing alternative goals with regard to family planning as well as other goals. (Fertil Steril (R) 2010; 93: 2321-9. (C)2010 by American Society for Reproductive Medicine.)
C1 [Davis, Mary; Wieners, Mary] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA.
[Ventura, June L.; Covington, Sharon N.; Vanderhoof, Vien H.; Popat, Vaishali B.; Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Ryan, Mary E.] Natl Inst Hlth Lib, Bethesda, MD USA.
[Koziol, Deloris E.; Nelson, Lawrence M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Nelson, LM (reprint author), NIH, Ctr Clin, CRC 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM Lawrence_Nelson@nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health
FX Supported by the Intramural Research Program of the National Institute
of Child Health and Human Development, National Institutes of Health. V.
H. V. and L.M.N. are commissioned officers in the United States Public
Health Service.
NR 80
TC 15
Z9 16
U1 4
U2 13
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 MAY 1
PY 2010
VL 93
IS 7
BP 2321
EP 2329
DI 10.1016/j.fertnstert.2008.12.122
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 595KD
UT WOS:000277608200035
PM 19243752
ER
PT J
AU Vazquez-Chantada, M
Fernandez-Ramos, D
Embade, N
Martinez-Lopez, N
Varela-Rey, M
Woodhoo, A
Luka, Z
Wagner, C
Anglim, PP
Finnell, RH
Caballeria, J
Laird-Offringa, IA
Gorospe, M
Lu, SC
Mato, JM
Martinez-Chantar, ML
AF Vazquez-Chantada, Mercedes
Fernandez-Ramos, David
Embade, Nieves
Martinez-Lopez, Nuria
Varela-Rey, Marta
Woodhoo, Ashwin
Luka, Zigmund
Wagner, Conrad
Anglim, Paul P.
Finnell, Richard H.
Caballeria, Juan
Laird-Offringa, Ite A.
Gorospe, Myriam
Lu, Shelly C.
Mato, Jose M.
Luz Martinez-Chantar, M.
TI HuR/Methyl-HuR and AUF1 Regulate the MAT Expressed During Liver
Proliferation, Differentiation, and Carcinogenesis
SO GASTROENTEROLOGY
LA English
DT Article
DE HuR; AUF1; MAT1A; MAT2A
ID METHIONINE ADENOSYLTRANSFERASE 1A; S-ADENOSYLMETHIONINE SYNTHETASE;
HUMAN HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA STABILITY;
GENE-EXPRESSION; BINDING-PROTEINS; CELL-PROLIFERATION; RAT HEPATOCYTES;
UP-REGULATION; 2A GENE
AB BACKGROUND & AIMS: Hepatic de-differentiation, liver development, and malignant transformation are processes in which the levels of hepatic S-adenosylmethionine are tightly regulated by 2 genes: methionine adenosyltransferase 1A (MAT1A) and methionine adenosyltransferase 2A (MAT2A). MAT1A is expressed in the adult liver, whereas MAT2A expression primarily is extrahepatic and is associated strongly with liver proliferation. The mechanisms that regulate these expression patterns are not completely understood. METHODS: In silico analysis of the 3' untranslated region of MAT1A and MAT2A revealed putative binding sites for the RNA-binding proteins AU-rich RNA binding factor 1 (AUF1) and HuR, respectively. We investigated the posttranscriptional regulation of MAT1A and MAT2A by AUF1, HuR, and methyl-HuR in the aforementioned biological processes. RESULTS: During hepatic de-differentiation, the switch between MAT1A and MAT2A coincided with an increase in HuR and AUF1 expression. S-adenosylmethionine treatment altered this homeostasis by shifting the balance of AUF1 and methyl-HuR/HuR, which was identified as an inhibitor of MAT2A messenger RNA (mRNA) stability. We also observed a similar temporal distribution and a functional link between HuR, methyl-HuR, AUF1, and MAT1A and MAT2A during fetal liver development. Immunofluorescent analysis revealed increased levels of HuR and AUF1, and a decrease in methyl-HuR levels in human livers with hepatocellular carcinoma (HCC). CONCLUSIONS: Our data strongly support a role for AUF1 and HuR/methyl-HuR in liver de-differentiation, development, and human HCC progression through the posttranslational regulation of MAT1A and MAT2A mRNAs.
C1 [Vazquez-Chantada, Mercedes; Fernandez-Ramos, David; Embade, Nieves; Martinez-Lopez, Nuria; Varela-Rey, Marta; Woodhoo, Ashwin; Mato, Jose M.; Luz Martinez-Chantar, M.] CIC bioGUNE, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Derio 48160, Bizkaia, Spain.
[Luka, Zigmund; Wagner, Conrad] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
[Wagner, Conrad] Tennessee Valley Dept Med Affairs Med Ctr, Nashville, TN USA.
[Anglim, Paul P.; Laird-Offringa, Ite A.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[Lu, Shelly C.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Finnell, Richard H.] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX USA.
[Caballeria, Juan] IDIBAPS, Liver Unit, Hosp Clin, Barcelona, Spain.
[Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Martinez-Chantar, ML (reprint author), CIC bioGUNE, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Technol Pk Bizkaia, Derio 48160, Bizkaia, Spain.
EM mlmartinez@cicbiogune.es
RI MATO, JOSE/A-5187-2011; embade, Nieves/K-5190-2014; woodhoo,
ashwin/A-4904-2015; Martinez Chantar, Maria Luz/F-5190-2011;
Fernandez-Ramos, David/S-5231-2016
OI embade, Nieves/0000-0001-9878-3290; woodhoo, ashwin/0000-0002-8395-2837;
Martinez Chantar, Maria Luz/0000-0002-6446-9911;
FU National Institutes of Health [DK51719, AT-1576, SAF2005-00855,
HEPADIP-EULSHM-CT-205, ETORTEK-2008, DK15289]; Catedra de Biomedicina de
la Fundacion Banco Bilbao Vizcaya [CAT06_002]; Program Ramon y Cajal del
MEC; Fundacion "La Caixa"; NIA-IRP, National Institutes of Health;
NIDDK-USC Liver Center; Institut de Salud Carlos III
FX This study was supported by National Institutes of Health grants DK51719
(to S.C.L.) and AT-1576 (to S.C.L., J.M.M., and M.L.M.-C.),
SAF2005-00855, HEPADIP-EULSHM-CT-205, and ETORTEK-2008 (to J.M.M. and
M.L.M.-C.); Catedra de Biomedicina de la Fundacion Banco Bilbao Vizcaya
grant CAT06_002 (to R.H.F. and J.M.M.); Program Ramon y Cajal del MEC
and Fundacion "La Caixa" (to M.L.M.-C.); National Institutes of Health
grant DK15289 (to C.W.); NIA-IRP, National Institutes of Health (M.G.);
pilot funds from the NIDDK-USC Liver Center (to I.A.L.-O.); and Centro
de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas
is funded by the Institut de Salud Carlos III.
NR 38
TC 41
Z9 43
U1 2
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAY
PY 2010
VL 138
IS 5
BP 1943
EP U97
DI 10.1053/j.gastro.2010.01.032
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 587LA
UT WOS:000276992600040
PM 20102719
ER
PT J
AU Sokolov, MV
Panyutin, IV
Onyshchenko, MI
Panyutin, IG
Neumann, RD
AF Sokolov, Mykyta V.
Panyutin, Irina V.
Onyshchenko, Mykola I.
Panyutin, Igor G.
Neumann, Ronald D.
TI Expression of pluripotency-associated genes in the surviving fraction of
cultured human embryonic stem cells is not significantly affected by
ionizing radiation
SO GENE
LA English
DT Article
DE Human embryonic stem cells; Genotoxic agent; Pluripotency marker;
Ionizing radiation; Directed differentiation
ID SELF-RENEWAL; HUMAN BLASTOCYSTS; DNA-DAMAGE; ES CELLS; DIFFERENTIATION;
APOPTOSIS; NANOG; P53; RESPONSES; NETWORK
AB Human embryonic stem cells (hESC) are capable to give rise to all cell types in the human body during the normal course of development. Therefore, these cells hold a great promise in regenerative cell replacement based therapeutical approaches. However, some controversy exists in literature concerning the ultimate fate of hESC after exposure to genotoxic agents, in particular, regarding the effect of DNA damaging insults on pluripotency of hESC. To comprehensively address this issue, we performed an analysis of the expression of marker genes, associated with pluripotent state of hESC, such as Oct-4, Nanog, Sox-2, SSEA-4, TERT, TRA-1-60 and TRA-1-81 up to 65 h after exposure to ionizing radiation (IR) using flow cytometry, immunocytochemistry and quantitative real-time polymerase chain reaction techniques. We show that irradiation with relatively low doses of gamma-radiation (0.2 Gy and 1 Gy) does not lead to loss of expression of the pluripotency-associated markers in the surviving hESC. While changes in the levels of expression of some of the pluripotency markers were observed at different time points after IR exposure, these alterations were not persistent, and, in most cases, the expression of the pluripotency-associated markers remained significantly higher than that observed in fully differentiated human fibroblasts, and in hESCs differentiated into definitive endodermal lineage. Our data suggest that exposure of hESC to relatively low doses of IR as a model genotoxic agent does not significantly affect pluripotency of the surviving fraction of hESC. Published by Elsevier B.V.
C1 [Sokolov, Mykyta V.; Panyutin, Irina V.; Onyshchenko, Mykola I.; Panyutin, Igor G.; Neumann, Ronald D.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Panyutin, IG (reprint author), 9000 Rockville Pike,Bldg 10,Room 1C492, Bethesda, MD 20892 USA.
EM sokolovm@mail.nih.gov; ipanyutinv@mail.nih.gov;
onyshchenkom@mail.nih.gov; ipanyuting@mail.nih.gov;
rneumann@mail.nih.gov
OI Onyshchenko, Mykola/0000-0003-4663-0991
FU Intramural Research Program of the NIH, Clinical Center
FX We thank W. DeGraff for his invaluable help with the cell culture
-y-irradiation. This research was supported by the Intramural Research
Program of the NIH, Clinical Center.
NR 29
TC 21
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD MAY 1
PY 2010
VL 455
IS 1-2
BP 8
EP 15
DI 10.1016/j.gene.2010.01.006
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 584OP
UT WOS:000276762300002
PM 20123005
ER
PT J
AU Nelson, EJR
Tuschong, LM
Hunter, MJ
Bauer, TR
Burkholder, TH
Hickstein, DD
AF Nelson, E. J. R.
Tuschong, L. M.
Hunter, M. J.
Bauer, T. R., Jr.
Burkholder, T. H.
Hickstein, D. D.
TI Lentiviral vectors incorporating a human elongation factor 1 alpha
promoter for the treatment of canine leukocyte adhesion deficiency
SO GENE THERAPY
LA English
DT Article
DE EF1 alpha promoter; lentiviral vector; ex vivo gene therapy; CLAD;
leukocyte adhesion; immunodeficiency
ID INTEGRIN CD18 SUBUNIT; DISEASE PHENOTYPE; GENE-THERAPY; TRANSGENE
EXPRESSION; CELLS; TRANSDUCTION; DELIVERY
AB Canine leukocyte adhesion deficiency (CLAD) provides a unique large animal model for testing new therapeutic approaches for the treatment of children with leukocyte adhesion deficiency (LAD). In our CLAD model, we examined two different fragments of the human elongation factor 1 alpha (EF1 alpha) promoter (EF1 alpha L, 1189 bp and EF1 alpha S, 233 bp) driving the expression of canine CD18 in a self-inactivating (SIN) lentiviral vector. The EF1 alpha S vector resulted in the highest levels of canine CD18 expression in CLAD CD34(+) cells in vitro. Subsequently, autologous CD34(+) bone marrow cells from four CLAD pups were transduced with the EF1 alpha S vector and infused following a non-myeloablative dose of 200 cGy total-body irradiation. None of the CLAD pups achieved levels of circulating CD18(+) neutrophils sufficient to reverse the CLAD phenotype, and all four animals were euthanized because of infections within 9 weeks of treatment. These results indicate that the EF1 alpha S promoter-driven CD18 expression in the context of a RRLSIN lentiviral vector does not lead to sufficient numbers of CD18(+) neutrophils in vivo to reverse the CLAD phenotype when used in a nonmyeloablative transplant regimen in dogs. Gene Therapy (2010) 17, 672-677; doi: 10.1038/gt.2010.7; published online 18 February 2010
C1 [Nelson, E. J. R.; Tuschong, L. M.; Hunter, M. J.; Bauer, T. R., Jr.; Hickstein, D. D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Burkholder, T. H.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Hickstein, DD (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1203,Bldg 10 CRC,Rm 3-3142, Bethesda, MD 20892 USA.
EM hicksted@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We thank
William Telford and Veena Kapoor, NCI, for assistance with flow
cytometry.
NR 19
TC 12
Z9 12
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD MAY
PY 2010
VL 17
IS 5
BP 672
EP 677
DI 10.1038/gt.2010.7
PG 6
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA 595CZ
UT WOS:000277589600011
PM 20164857
ER
PT J
AU Cornelis, MC
Agrawal, A
Cole, JW
Hansel, NN
Barnes, KC
Beaty, TH
Bennett, SN
Bierut, LJ
Boerwinkle, E
Doheny, KF
Feenstra, B
Feingold, E
Fornage, M
Haiman, CA
Harris, EL
Hayes, MG
Heit, JA
Hu, FB
Kang, JH
Laurie, CC
Ling, H
Manolio, TA
Marazita, ML
Mathias, RA
Mirel, DB
Paschall, J
Pasquale, LR
Pugh, EW
Rice, JP
Udren, J
van Dam, RM
Wang, XJ
Wiggs, JL
Williams, K
Yu, K
AF Cornelis, Marilyn C.
Agrawal, Arpana
Cole, John W.
Hansel, Nadia N.
Barnes, Kathleen C.
Beaty, Terri H.
Bennett, Siiri N.
Bierut, Laura J.
Boerwinkle, Eric
Doheny, Kimberly F.
Feenstra, Bjarke
Feingold, Eleanor
Fornage, Myriam
Haiman, Christopher A.
Harris, Emily L.
Hayes, M. Geoffrey
Heit, John A.
Hu, Frank B.
Kang, Jae H.
Laurie, Cathy C.
Ling, Hua
Manolio, Teri A.
Marazita, Mary L.
Mathias, Rasika A.
Mirel, Daniel B.
Paschall, Justin
Pasquale, Louis R.
Pugh, Elizabeth W.
Rice, John P.
Udren, Jenna
van Dam, Rob M.
Wang, Xiaojing
Wiggs, Janey L.
Williams, Kayleen
Yu, Kai
CA GENEVA Consortium
TI The Gene, Environment Association Studies Consortium (GENEVA):
Maximizing the Knowledge Obtained from GWAS by Collaboration Across
Studies of Multiple Conditions
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE genome-wide association; complex disease; quantitative traits;
gene-environment interaction; phenotype harmonization
ID GENOME-WIDE ASSOCIATION; RISK; HETEROGENEITY; POPULATION; DISEASES;
CANCER
AB Genome-wide association studies (GWAS) have emerged as powerful means for identifying genetic loci related to complex diseases. However, the role of environment and its potential to interact with key loci has not been adequately addressed in most GWAS. Networks of collaborative studies involving different study populations and multiple phenotypes provide a powerful approach for addressing the challenges in analysis and interpretation shared across studies. The Gene, Environment Association Studies (GENEVA) consortium was initiated to: identify genetic variants related to complex diseases; identify variations in gene-trait associations related to environmental exposures; and ensure rapid sharing of data through the database of Genotypes and Phenotypes. GENEVA consists of several academic institutions, including a coordinating center, two genotyping centers and 14 independently designed studies of various phenotypes, as well as several Institutes and Centers of the National Institutes of Health led by the National Human Genome Research Institute. Minimum detectable effect sizes include relative risks ranging from 1.24 to 1.57 and proportions of variance explained ranging from 0.0097 to 0.02. Given the large number of research participants (N > 80,000), an important feature of GENEVA is harmonization of common variables, which allow analyses of additional traits. Environmental exposure information available from most studies also enables testing of gene-environment interactions. Facilitated by its sizeable infrastructure for promoting collaboration, GENEVA has established a unified framework for genotyping, data quality control, analysis and interpretation. By maximizing knowledge obtained through collaborative GWAS incorporating environmental exposure information, GENEVA aims to enhance our understanding of disease etiology, potentially identifying opportunities for intervention. Genet. Epidemiol. 34:364-372, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Cornelis, Marilyn C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Agrawal, Arpana; Bierut, Laura J.; Rice, John P.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Cole, John W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Hansel, Nadia N.; Barnes, Kathleen C.; Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Beaty, Terri H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Bennett, Siiri N.; Laurie, Cathy C.; Udren, Jenna; Williams, Kayleen] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Doheny, Kimberly F.; Ling, Hua; Pugh, Elizabeth W.] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA.
[Feenstra, Bjarke] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Feingold, Eleanor] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
[Fornage, Myriam] Univ Texas Houston, Inst Mol Med, Houston, TX USA.
[Haiman, Christopher A.] Univ S Carolina, Keck Sch Med, Los Angeles, CA USA.
[Harris, Emily L.] Natl Inst Dent & Craniofacial Res, US NIH, Bethesda, MD USA.
[Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Heit, John A.] Mayo Clin, Div Hematol, Rochester, MN USA.
[Kang, Jae H.; Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Marazita, Mary L.; Wang, Xiaojing] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA USA.
[Mirel, Daniel B.] MIT & Harvard, Broad Inst, Boston, MA USA.
[Paschall, Justin] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Yu, Kai] NCI, NIH, Bethesda, MD 20892 USA.
RP Cornelis, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM mcorneli@hsph.harvard.edu
RI van Dam, Rob/F-9674-2010;
OI van Dam, Rob/0000-0002-7354-8734; Feenstra, Bjarke/0000-0003-1478-649X;
Feingold, Eleanor/0000-0003-2898-6484
FU NIH [U01HG04424, U01HG004438, HHSN268200782096C, U01HG004422,
U01HG004402, HHSN268200625226C, Z01CP010200, U01HG004729, U01HG004399,
U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423,
U01HG004728]; NIDCR [U01DE018993]; NIAAA [U10AA008401]; NIDA
[P01CA089392, R01DA013423]; NHLBI [N01HC55015, N01HC55016, N01HC55018,
N01HC55019, N01HC-55020, N01HC-55021, N01HC55022, R01HL087641,
R01HL59367, R01HL086694]; NIH Roadmap for Medical Research
[UL1RR025005]; NCI [CA63464, CA54281, CA136792]; NET [R01EY015473,
R01EY015872]; National Library of Medicine; Canadian Institutes of
Health Research; National Center for Research Resources (NCRR)
FX Contract grant sponsor: NIH Genes, Environment and Health Initiative
(GEI); Contract grant numbers: U01HG04424; U01HG004438; Contract grant
sponsor: NIDCR; Contract grant number: U01DE018993; Contract grant
sponsor: NIH; Contract grant numbers: HHSN268200782096C; U01HG004422;
HHSN268200782096C; U01HG004402; HHSN268200625226C; Z01CP010200;
U01HG004729; U01HG004399; U01HG004726; U01HG004735; U01HG004415;
HHSN268200782096C; U01HG004436; U01HG004423; U01HG004728;
HHSN268200782096C; Contract grant sponsor: NIAAA; Contract grant number:
U10AA008401; Contract grant sponsor: NIDA; Contract grant numbers:
P01CA089392; R01DA013423; Contract grant sponsor: NHLBI; Contract grant
numbers: N01HC55015; N01HC55016; N01HC55018; N01HC55019; N01HC-55020;
N01HC-55021; N01HC55022; R01HL087641; R01HL59367; R01HL086694; Contract
grant sponsor: NIH Roadmap for Medical Research; Contract grant number:
UL1RR025005; Contract grant sponsor: NCI; Contract grant numbers:
CA63464; CA54281; CA136792; Contract grant sponsor: NIDCR; Contract
grant number: U01DE018903; Contract grant sponsor: NET; Contract grant
numbers: R01EY015473; R01EY015872; Contract grant sponsors: National
Library of Medicine; Canadian Institutes of Health Research Fellowship;
National Center for Research Resources (NCRR).
NR 25
TC 85
Z9 85
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2010
VL 34
IS 4
BP 364
EP 372
DI 10.1002/gepi.20492
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 595VY
UT WOS:000277642800009
PM 20091798
ER
PT J
AU Lachance, CR
Erby, LAH
Ford, BM
Allen, VC
Kaphingst, KA
AF Lachance, Christina R.
Erby, Lori A. H.
Ford, Beth M.
Allen, Vincent C., Jr.
Kaphingst, Kimberly A.
TI Informational content, literacy demands, and usability of websites
offering health-related genetic tests directly to consumers
SO GENETICS IN MEDICINE
LA English
DT Article
DE direct-to-consumer; genetic testing; Internet; health literacy;
usability
ID UNITED-STATES; READABILITY FORMULA; INTERNET; CANCER; RISK; GENOME
AB Purpose: As direct-to-consumer genetic testing becomes more available, a diverse group of consumers, including those with limited health literacy, may consider testing. In light of concerns raised about direct-to-consumer genetic testing, this study sought to critically examine whether the informational content, literacy demands, and usability of health-related direct-to-consumer websites met existing recommendations. Methods: A content analysis was performed on 29 health-related direct-to-consumer websites. Two coders independently evaluated each website for informational content (e.g., benefits, limitations), literacy demands (e.g., reading level), and usability (e. g., ease of navigation). Results: Most sites presented health conditions and some markers for which they tested, benefits of testing, a description of the testing process, and their privacy policy. Fewer cited scientific literature, explained test limitations, or provided an opportunity to consult a health professional. Key informational content was difficult to locate on most sites. Few sites gave sample disease risk estimates or used common language and explained technical terms consistently. Average reading level was grade 15. Conclusion: The quality of informational content, literacy demands, and usability across health-related direct-to-consumer websites varied widely. Many users would struggle to find and understand the important information. For consumers to better understand the content on these sites and evaluate the meaning of the tests for their health, sites should lower the demands placed on users by distilling and prioritizing the key informational content while simultaneously attending to the reading level and usability elements. In the absence of regulation compelling such changes, government agencies or professional organizations may need to increase consumer and provider awareness of these issues. Genet Med 2010: 2(5):304-312.
C1 [Lachance, Christina R.; Ford, Beth M.; Allen, Vincent C., Jr.; Kaphingst, Kimberly A.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Erby, Lori A. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA.
RP Kaphingst, KA (reprint author), Hlth Commun Res Lab, 700 Rosedale Ave,Campus Box 1009, St Louis, MO 63112 USA.
EM kkaphingst@gwbmail.wustl.edu
RI Norfadzila, Syarifah/G-9607-2012
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.
NR 44
TC 46
Z9 46
U1 2
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD MAY
PY 2010
VL 12
IS 5
BP 304
EP 312
DI 10.1097/GIM.0b013e3181dbd8b2
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 595GJ
UT WOS:000277598400008
PM 20386454
ER
PT J
AU Gotea, V
Visel, A
Westlund, JM
Nobrega, MA
Pennacchio, LA
Ovcharenko, I
AF Gotea, Valer
Visel, Axel
Westlund, John M.
Nobrega, Marcelo A.
Pennacchio, Len A.
Ovcharenko, Ivan
TI Homotypic clusters of transcription factor binding sites are a key
component of human promoters and enhancers
SO GENOME RESEARCH
LA English
DT Article
ID CIS-REGULATORY MODULES; GENOME-WIDE PREDICTION; FUNCTIONAL BINDING;
GENE-EXPRESSION; DISTAL ENHANCER; CPG ISLANDS; DNA; ZEBRAFISH; SEQUENCE;
ELEMENTS
AB Clustering of multiple transcription factor binding sites (TFBSs) for the same transcription factor (TF) is a common feature of cis-regulatory modules in invertebrate animals, but the occurrence of such homotypic clusters of TFBSs (HCTs) in the human genome has remained largely unknown. To explore whether HCTs are also common in human and other vertebrates, we used known binding motifs for vertebrate TFs and a hidden Markov model-based approach to detect HCTs in the human, mouse, chicken, and fugu genomes, and examined their association with cis-regulatory modules. We found that evolutionarily conserved HCTs occupy nearly 2% of the human genome, with experimental evidence for individual TFs supporting their binding to predicted HCTs. More than half of the promoters of human genes contain HCTs, with a distribution around the transcription start site in agreement with the experimental data from the ENCODE project. In addition, almost half of the 487 experimentally validated developmental enhancers contain them as well-a number more than 25-fold larger than expected by chance. We also found evidence of negative selection acting on TFBSs within HCTs, as the conservation of TFBSs is stronger than the conservation of sequences separating them. The important role of HCTs as components of developmental enhancers is additionally supported by a strong correlation between HCTs and the binding of the enhancer-associated coactivator protein Ep300 (also known as p300). Experimental validation of HCT-containing elements in both zebrafish and mouse suggest that HCTs could be used to predict both the presence of enhancers and their tissue specificity, and are thus a feature that can be effectively used in deciphering the gene regulatory code. In conclusion, our results indicate that HCTs are a pervasive feature of human cis-regulatory modules and suggest that they play an
C1 [Gotea, Valer; Ovcharenko, Ivan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Visel, Axel; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA.
[Visel, Axel; Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Westlund, John M.; Nobrega, Marcelo A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP Ovcharenko, I (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ovcharen@nih.gov
RI Visel, Axel/A-9398-2009;
OI Visel, Axel/0000-0002-4130-7784; Gotea, Valer/0000-0001-7857-3309
FU National Institutes of Health [HG004428]; National Library of Medicine;
National Human Genome Research Institute [HG003988]; National Heart,
Lung and Blood Institute [HL088393, HL066681]; Department of Energy
[DE-AC02-05CH11231]; University of California; E.O. Lawrence Berkeley
National Laboratory
FX This research was supported by the Intramural Research Program of the
National Institutes of Health; National Library of Medicine (V.G.,
I.O.); National Institutes of Health grants HG004428 (National Human
Genome Research Institute) and HL088393 (National Heart, Lung and Blood
Institute) (M.A.N., J.M.W.); and the Department of Energy Contract
DE-AC02-05CH11231, University of California, E.O. Lawrence Berkeley
National Laboratory (A.V., L.A.P.). L.A.P. was also supported by grant
HL066681, Berkeley-Program for Genomic Applications, under the Programs
for Genomic Applications, funded by the National Heart, Lung and Blood
Institute, and HG003988 funded by the National Human Genome Research
Institute.
NR 75
TC 110
Z9 110
U1 1
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 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2010
VL 20
IS 5
BP 565
EP 577
DI 10.1101/gr.104471.109
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 590RK
UT WOS:000277244800003
PM 20363979
ER
PT J
AU Volinia, S
Galasso, M
Costinean, S
Tagliavini, L
Gamberoni, G
Drusco, A
Marchesini, J
Mascellani, N
Sana, ME
Abu Jarour, R
Desponts, C
Teitell, M
Baffa, R
Aqeilan, R
Iorio, MV
Taccioli, C
Garzon, R
Di Leva, G
Fabbri, M
Catozzi, M
Previati, M
Ambs, S
Palumbo, T
Garofalo, M
Veronese, A
Bottoni, A
Gasparini, P
Harris, CC
Visone, R
Pekarsky, Y
de la Chapelle, A
Bloomston, M
Dillhoff, M
Rassenti, LZ
Kipps, TJ
Huebner, K
Pichiorri, F
Lenze, D
Cairo, S
Buendia, MA
Pineau, P
Dejean, A
Zanesi, N
Rossi, S
Calin, GA
Liu, CG
Palatini, J
Negrini, M
Vecchione, A
Rosenberg, A
Croce, CM
AF Volinia, Stefano
Galasso, Marco
Costinean, Stefan
Tagliavini, Luca
Gamberoni, Giacomo
Drusco, Alessandra
Marchesini, Jlenia
Mascellani, Nicoletta
Sana, Maria Elena
Abu Jarour, Ramzey
Desponts, Caroline
Teitell, Michael
Baffa, Raffaele
Aqeilan, Rami
Iorio, Marilena V.
Taccioli, Cristian
Garzon, Ramiro
Di Leva, Gianpiero
Fabbri, Muller
Catozzi, Marco
Previati, Maurizio
Ambs, Stefan
Palumbo, Tiziana
Garofalo, Michela
Veronese, Angelo
Bottoni, Arianna
Gasparini, Pierluigi
Harris, Curtis C.
Visone, Rosa
Pekarsky, Yuri
de la Chapelle, Albert
Bloomston, Mark
Dillhoff, Mary
Rassenti, Laura Z.
Kipps, Thomas J.
Huebner, Kay
Pichiorri, Flavia
Lenze, Dido
Cairo, Stefano
Buendia, Marie-Annick
Pineau, Pascal
Dejean, Anne
Zanesi, Nicola
Rossi, Simona
Calin, George A.
Liu, Chang-Gong
Palatini, Jeff
Negrini, Massimo
Vecchione, Andrea
Rosenberg, Anne
Croce, Carlo M.
TI Reprogramming of miRNA networks in cancer and leukemia
SO GENOME RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; CELL-CYCLE ARREST; MICRORNA EXPRESSION;
CAENORHABDITIS-ELEGANS; REGULATORY MODULES; BREAST-CANCER; LIVER-CANCER;
TARGET GENES; STEM-CELLS; DIFFERENTIATION
AB We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network.
C1 [Volinia, Stefano; Costinean, Stefan; Drusco, Alessandra; Aqeilan, Rami; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Huebner, Kay; Pichiorri, Flavia; Zanesi, Nicola; Palatini, Jeff; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Volinia, Stefano; Galasso, Marco; Tagliavini, Luca; Gamberoni, Giacomo; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Catozzi, Marco; Previati, Maurizio; Negrini, Massimo] Univ Ferrara, Dept Morphol & Embryol, I-44100 Ferrara, Italy.
[Abu Jarour, Ramzey; Desponts, Caroline] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Teitell, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
[Baffa, Raffaele] Thomas Jefferson Univ, Dept Urol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Iorio, Marilena V.] Ist Tumori, I-20133 Milan, Italy.
[Ambs, Stefan; Harris, Curtis C.] NIH, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Rassenti, Laura Z.; Kipps, Thomas J.] Univ Calif San Diego, Dept Med, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Lenze, Dido] Charite, Inst Pathol, D-10117 Berlin, Germany.
[Cairo, Stefano; Buendia, Marie-Annick] Inst Pasteur, Oncogenesis & Mol Virol Unit, F-75251 Paris 05, France.
[Pineau, Pascal; Dejean, Anne] Inst Pasteur, INSERM, U993, Nucl Org & Oncogenesis Unit, F-75724 Paris 15, France.
[Rossi, Simona; Calin, George A.; Liu, Chang-Gong] MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Vecchione, Andrea] II Univ Rome La Sapienza, Div Pathol, Osped Santo Andrea, I-00189 Rome, Italy.
[Rosenberg, Anne] Thomas Jefferson Univ, Coll Med, Dept Surg, Philadelphia, PA 19107 USA.
RP Croce, CM (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
EM carlo.croce@osumc.edu
RI Taccioli, Cristian/F-8801-2010; Garzon, Ramiro/E-3104-2011; Volinia,
Stefano/A-3029-2010; Negrini, Massimo/J-2377-2016; marchesini,
jlenia/K-2872-2016; Cairo, Stefano/O-2831-2016; Aqeilan,
Rami/R-4443-2016; Iorio, Marilena/K-5446-2016
OI Veronese, Angelo/0000-0002-1451-1392; Galasso,
Marco/0000-0003-2655-4792; Taccioli, Cristian/0000-0003-2995-5612;
Volinia, Stefano/0000-0003-0910-3893; Negrini,
Massimo/0000-0002-0007-1920; marchesini, jlenia/0000-0002-1911-5938;
Cairo, Stefano/0000-0002-4725-5970; Aqeilan, Rami/0000-0002-6034-023X;
Iorio, Marilena/0000-0002-6058-1527
FU AIRC [IG 8588, IG 5573]; PRIN MIUR [2008]; Regione Emilia Romagna
PRRIITT BioPharmaNet grants
FX S. V. is supported by AIRC (IG 8588), PRIN MIUR 2008, and Regione Emilia
Romagna PRRIITT BioPharmaNet grants; A.V. is supported by AIRC (IG
5573). Microarray analyses were performed using BRB-ArrayTools developed
by Richard Simon and the BRB-ArrayTools Development Team, GenePattern
(Broad Institute), BioConductor and R.
NR 53
TC 187
Z9 193
U1 1
U2 38
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2010
VL 20
IS 5
BP 589
EP 599
DI 10.1101/gr.098046.109
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 590RK
UT WOS:000277244800005
PM 20439436
ER
PT J
AU Huh, WK
Sill, MW
Darcy, KM
Elias, KM
Hoffman, JS
Boggess, JF
Alvarez, RD
Long, HJ
O'Malley, DM
Birrer, MJ
AF Huh, Warner K.
Sill, Michael W.
Darcy, Kathleen M.
Elias, Kevin M.
Hoffman, James S.
Boggess, John F.
Alvarez, Ronald D.
Long, Harry J.
O'Malley, David M.
Birrer, Michael J.
TI Efficacy and safety of imatinib mesylate (Gleevec (R)) and
immunohistochemical expression of c-Kit and PDGFR-beta in a Gynecologic
Oncology Group Phase II Trial in women with recurrent or persistent
carcinosarcomas of the uterus
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Carcinosarcoma; c-Kit; Uterus; PDGFR; Imatinib
ID GASTROINTESTINAL-STROMAL-TUMORS; CELL LUNG-CANCER; UTERINE SARCOMAS;
MESENCHYMAL TUMORS; CONTINGENCY-TABLES; MOLECULAR TARGETS; THERAPY;
PROTEIN; ALPHA; IFOSFAMIDE
AB Purpose. This multi-institutional phase II trial assessed the activity and toxicity of imatinib mesylate and explored c-Kit and platelet-derived growth factor receptor (PDGFR)-beta in recurrent or persistent uterine carcinosarcoma.
Methods. Women with measurable uterine carcinosarcoma, who had a performance status of 0, 1, or 2 and had received up to two prior treatment regimens, were eligible and treated with a 600-mg daily oral dose of imatinib mesylate until disease progression or unacceptable toxicity. Endpoints included progression-free survival (PFS) >= 6 months, overall toxicity, PFS, overall survival (OS), and response. c-Kit and PDGFR-beta were evaluated by immunohistochemistry in archival tumor.
Results. Twenty-six women were enrolled, 23 were eligible/evaluable, 1 was ineligible (wrong primary), and 2 were inevaluable (never treated). One subject had a PFS time >= 6 months, yielding the only patient with stable disease. All other patients had progressive disease (n = 17) or were inevaluable for tumor response (n = 5). Adverse events included grade 4 hypocalcemia (n = 1) and grade 3 fatigue, dehydration and anorexia, genitourinary/renal, lymphatic, metabolic, and ocular toxicity (n = 1 each, 4%). Positive expression of c-Kit or PDGFR-beta was observed in 88% (14/16) or 40% (6/15) and in 56% (9/16) or 73% (11/15) of cases in the sarcoma and carcinoma component of the tumor, respectively. Expression of c-Kit in the carcinoma component appeared to be associated with worse OS. No other associations were notable.
Conclusion. Imatinib mesylate was generally well tolerated but had minimal activity as a single agent in unscreened patients. The potential association between carcinomatous c-Kit and OS requires validation. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Huh, Warner K.; Alvarez, Ronald D.] Univ Alabama, Div Gynecol Oncol, Birmingham, AL USA.
[Sill, Michael W.; Darcy, Kathleen M.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
[Sill, Michael W.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA.
[Elias, Kevin M.; Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hoffman, James S.] Tufts Univ New England Med Ctr, Boston, MA USA.
[Boggess, John F.] Univ N Carolina, Div Obstet & Gynecol, Chapel Hill, NC USA.
[Long, Harry J.] Mayo Clin, Dept Med Oncol, Rochester, MN USA.
[O'Malley, David M.] Ohio State Univ, Coll Med, Dept Gynecol Oncol, Columbus, OH 43210 USA.
RP Huh, WK (reprint author), 618 20th St S,OHB Room 538, Birmingham, AL 35233 USA.
EM warner.huh@ccc.uab.edu
RI OMalley, David/E-3789-2011
FU National Cancer Institute [CA 27469, CA 11479, CA 37517]; National
Cancer Institute of the National Institute of Health
FX This study was supported by National Cancer Institute grants to the
Gynecologic Oncology Group (COG) Administrative Office (CA 27469), the
COG Tissue Bank (CA 11479) and the COG Statistical and Data Center (CA
37517), and the Intramural Research Program of the National Cancer
Institute of the National Institute of Health. The following Gynecologic
Oncology Group member institutions participated in this study:
University of Alabama at Birmingham, Abington Memorial Hospital,
University of Pennsylvania Cancer Center, University of Cincinnati,
University of North Carolina School of Medicine, Indiana University
School of Medicine, Tufts-New England Medical Center, SUNY Downstate
Medical Center, The Cleveland Clinic Foundation, Columbus Cancer
Council, University of Oklahoma, Mayo Clinic, and Community Clinical
Oncology Program.
NR 42
TC 26
Z9 26
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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAY
PY 2010
VL 117
IS 2
BP 248
EP 254
DI 10.1016/j.ygyno.2010.01.002
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LG
UT WOS:000277538600016
PM 20189232
ER
PT J
AU Minig, L
Zanagnolo, V
Maggioni, A
AF Minig, Lucas
Zanagnolo, Vanna
Maggioni, Angelo
TI Robotic approach for cervical cancer: Comparison with laparotomy. A case
control study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Letter
ID LAPAROSCOPIC RADICAL HYSTERECTOMY
C1 [Minig, Lucas] NCI, Div Canc Treatment & Diag, Nihon Univ, Bethesda, MD 20892 USA.
[Minig, Lucas; Zanagnolo, Vanna; Maggioni, Angelo] European Inst Oncol, Dept Gynecol, Milan, Italy.
RP Minig, L (reprint author), NCI, Div Canc Treatment & Diag, Nihon Univ, Bldg 10 B3B69C, Bethesda, MD 20892 USA.
EM lucasminig@yahoo.com
NR 7
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAY
PY 2010
VL 117
IS 2
BP 389
EP 390
DI 10.1016/j.ygyno.2010.01.033
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LG
UT WOS:000277538600043
ER
PT J
AU Wimmer, K
Kratz, CP
AF Wimmer, Katharina
Kratz, Christian P.
TI Constitutional mismatch repair-deficiency syndrome
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Editorial Material
ID EARLY-ONSET; NEUROFIBROMATOSIS TYPE-1; HEMATOLOGICAL MALIGNANCY; MSH6
MUTATIONS; GENE; PREDISPOSES; LEUKEMIA; CANCERS
C1 [Wimmer, Katharina] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Human Genet, Innsbruck, Austria.
[Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Wimmer, K (reprint author), Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Human Genet, Innsbruck, Austria.
EM katharina.wimmer@i-med.ac.at
FU Intramural NIH HHS
NR 23
TC 38
Z9 38
U1 1
U2 6
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD MAY
PY 2010
VL 95
IS 5
BP 699
EP 701
DI 10.3324/haematol.2009.021626
PG 3
WC Hematology
SC Hematology
GA 600GR
UT WOS:000277974000003
PM 20442441
ER
PT J
AU Anastasov, N
Bonzheim, I
Rudelius, M
Klier, M
Dau, T
Angermeier, D
Duyster, J
Pittaluga, S
Fend, F
Raffeld, M
Quintanilla-Martinez, L
AF Anastasov, Natasa
Bonzheim, Irina
Rudelius, Martina
Klier, Margit
Dau, Therese
Angermeier, Daniela
Duyster, Justus
Pittaluga, Stefania
Fend, Falko
Raffeld, Mark
Quintanilla-Martinez, Leticia
TI C/EBP beta expression in ALK-positive anaplastic large cell lymphomas is
required for cell proliferation and is induced by the STAT3 signaling
pathway
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE anaplastic large cell lymphoma (ALCL); C/EBP beta; STAT3; RNA
interference; cell proliferation
ID BINDING-PROTEIN-BETA; TYROSINE KINASE; GROWTH-HORMONE; MESSENGER-RNA;
CYCLIN D1; TRANSCRIPTION; ACTIVATION; CANCER; TARGET; PHOSPHORYLATION
AB Background
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is characterized by the t(2;5) chromosomal translocation, resulting in the expression of a fusion protein formed of nucleophosmin (NPM) and ALK. Recently, we reported the abnormal expression of the transcription factor CCAAT/enhancer binding protein-beta (C/EBP beta) in ALK-positive anaplastic large cell lymphomas, and demonstrated its dependence on NPM-ALK activity.
Design and Methods
In this study, the role of C/EBP beta in proliferation and survival of ALK-positive anaplastic large cell lymphomas was investigated, as well as the mechanism of its expression and activity. Highly effective short hairpin RNA sequences and/or pharmacological inhibitors were used to abrogate the expression or activity of C/EBP beta, signal transducer and activator of transcription 3 (STAT3), AKT, extracellular signal-related kinase 1/2 (ERK1/2) and mammalian target of rapamycin (mTOR).
Results
Interference with C/EBP beta expression resulted in a dramatic decrease in cell proliferation in ALK-positive anaplastic large cell lymphomas, with a mild induction of apoptosis after 6 days. Down-regulation of STAT3 resulted in a marked decrease in C/EBP beta mRNA and protein levels with impairment in cell proliferation and viability, underscoring the important role of these two proteins in ALK-mediated oncogenesis. Additionally, we demonstrated that reduction of ERK1/2 activity led to C/EBP beta Thr(235) dephosphorylation and moderate growth retardation. The AKT/mTOR signaling pathway did not have any influence on C/EBP beta expression or C/EBP beta phosphorylation.
Conclusions
These findings reveal the convergence of STAT3 and ERK1/2 signaling pathways activated by NPM-ALK in mediating the regulation of C/EBP beta expression, a transcription factor central to NPM-ALK transformation.
C1 [Anastasov, Natasa; Dau, Therese; Angermeier, Daniela; Quintanilla-Martinez, Leticia] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Pathol, Munich, Germany.
[Anastasov, Natasa] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Radiat Biol, Munich, Germany.
[Bonzheim, Irina; Klier, Margit; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, D-7400 Tubingen, Germany.
[Bonzheim, Irina; Klier, Margit; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Hosp & Comprehens Canc Ctr, Tubingen, Germany.
[Rudelius, Martina; Angermeier, Daniela] Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany.
[Duyster, Justus] Tech Univ Munich, Internal Med 3, D-8000 Munich, Germany.
[Pittaluga, Stefania; Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Quintanilla-Martinez, L (reprint author), Univ Tubingen Hosp, Inst Pathol, Liebermeisterstr 8, D-72076 Tubingen, Germany.
EM leticia.quintanilla-fend@med.uni-tuebingen.de
RI Anastasov, Natasa/M-9848-2014
OI Anastasov, Natasa/0000-0002-4088-1119
FU Deutsche Forschungsgemeinschaft [SFB-685]
FX Funding: supported in part by a grant from the Deutsche
Forschungsgemeinschaft (SFB-685) to LQ-M and FF
NR 34
TC 26
Z9 27
U1 0
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD MAY
PY 2010
VL 95
IS 5
BP 760
EP 767
DI 10.3324/haematol.2009.014050
PG 8
WC Hematology
SC Hematology
GA 600GR
UT WOS:000277974000013
PM 20015877
ER
PT J
AU James, AH
Hoots, K
AF James, A. H.
Hoots, K.
TI The optimal mode of delivery for the haemophilia carrier expecting an
affected infant is caesarean delivery
SO HAEMOPHILIA
LA English
DT Review
DE caesarean delivery; childbirth; haemophilia carrier; pregnancy
ID VAGINAL DELIVERY; TERM; OUTCOMES; SECTION; TRENDS; TRIAL
AB While a majority of affected infants of haemophilia carriers who deliver vaginally do not suffer a head bleed, the outcome of labour cannot be predicted. A planned vaginal delivery puts a woman at risk of an abnormal labour and operative vaginal delivery, both of which predispose to intracranial haemorrhage. Furthermore, vaginal delivery does not eliminate the risk to the haemophilia carrier herself. Overall, maternal morbidity and mortality from planned vaginal delivery are not significantly different from those from planned caesarean delivery. Caesarean delivery is recommended or elected now in conditions other than haemophilia carriage, where the potential benefits are not nearly as great. Additionally, vaginal delivery of the haemophilia carrier poses medical/legal risks if the infant is born with cephalohaematoma or intracranial haemorrhage. Caesarean delivery allows for a planned, controlled delivery. Caesarean delivery reduces the risk of intracranial haemorrhage by an estimated 85% and the risk can be nearly eliminated by performing elective caesarean delivery before labour. Therefore, after a discussion of the maternal and foetal risks with planned vaginal delivery versus planned caesarean delivery, haemophilia carriers should be offered the option of an elective caesarean delivery.
C1 [James, A. H.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Durham, NC 27710 USA.
[Hoots, K.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
RP James, AH (reprint author), Box 3967 DUMC, Durham, NC 27710 USA.
EM andra.james@duke.edu
NR 20
TC 29
Z9 29
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD MAY
PY 2010
VL 16
IS 3
BP 420
EP 424
DI 10.1111/j.1365-2516.2009.02142.x
PG 5
WC Hematology
SC Hematology
GA 587OC
UT WOS:000277001100002
PM 20028425
ER
PT J
AU Kim, Z
Kim, J
Kim, MJ
Hur, KY
Choi, D
Seo, D
Kim, JH
Lee, KJ
Nakao, A
AF Kim, Zisun
Kim, Jeongman
Kim, Min Joo
Hur, Kyung Yul
Choi, Dongho
Seo, Daekwan
Kim, Jung Hoon
Lee, Kyung-Jae
Nakao, Akimasa
TI Negative Pressure External Drainage of the Pancreatic Duct in
Pancreaticoduodenectomy
SO HEPATO-GASTROENTEROLOGY
LA English
DT Article
DE Negative pressure; External drainage; Pancreaticoduodenectomy
ID PROSPECTIVE RANDOMIZED-TRIAL; CONSECUTIVE PANCREATICODUODENECTOMIES;
RISK-FACTORS; TO-MUCOSA; PANCREATICOJEJUNOSTOMY; FISTULA; COMPLICATIONS;
DECREASE; RECONSTRUCTION; EXPERIENCE
AB Background/Aims: Despite the development of surgical techniques, postoperative pancreatic fistula is still one of the main causes of serious morbidity after pancreaticoduodenectomy. Nevertheless numerous studies have been done, studies on preventing pancreatic fistula are lacking. This study is focused on the effectiveness of negative pressure external drainage for pancreaticojejunostomy in pancreaticoduodenectomy patients.
Methodology: Seventy-six patients were scheduled for pancreaticoduodenectomy at Soonchunhyang University Hospital from January of 2003 to August of 2007. Negative suction drainage group (n=41) and no negative suction drainage group (n=35) were compared by patient characteristics, parameters related to operation, and complications.
Results: There were no statistical differences between both groups in patient demographics and parameters related to operation. The complication rates were significantly lower in negative suction drainage group in terms of postoperative bleeding (P = 0.012), choledochojejunostomy leak (P = 0.014), and pancreatic fistula (P = 0.018).
Conclusions: This retrospective study showed that external stenting with negative pressure suction drainage of the pancreatic duct has significantly reduced the rate of pancreatic fistula in duct-to-mucosa pancreaticojejunostomy with improved surgical outcomes.
C1 [Kim, Zisun; Kim, Jeongman; Kim, Min Joo; Hur, Kyung Yul; Choi, Dongho] Soonchunhyang Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Seo, Daekwan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kim, Jung Hoon] Soonchunhyang Univ, Coll Med, Dept Radiol, Seoul, South Korea.
[Lee, Kyung-Jae] Soonchunhyang Univ, Coll Med, Dept Occupat Med, Seoul, South Korea.
[Nakao, Akimasa] Nagoya Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 466, Japan.
RP Choi, D (reprint author), Soonchunhyang Univ Hosp, Dept Surg, Seoul 140743, South Korea.
EM dhchoi@hosp.sch.ac.kr
NR 34
TC 7
Z9 7
U1 1
U2 1
PU H G E UPDATE MEDICAL PUBLISHING S A
PI ATHENS
PA PO BOX 17257, ATHENS GR-10024, GREECE
SN 0172-6390
J9 HEPATO-GASTROENTEROL
JI Hepato-Gastroenterol.
PD MAY-JUN
PY 2010
VL 57
IS 99-100
BP 625
EP 630
PG 6
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 634CU
UT WOS:000280557900045
PM 20698239
ER
PT J
AU Everhart, JE
Bambha, KM
AF Everhart, James E.
Bambha, Kiran M.
TI Fatty Liver: Think Globally
SO HEPATOLOGY
LA English
DT Editorial Material
ID RISK-FACTORS; INSULIN-RESISTANCE; ASIAN INDIANS; HEPATIC STEATOSIS;
UNITED-STATES; PREVALENCE; DISEASE; ASSOCIATION; POPULATION; OBESITY
C1 [Everhart, James E.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Bambha, Kiran M.] Univ Colorado Hlth Sci, Dept Med, Aurora, CO USA.
RP Everhart, JE (reprint author), NIDDKD, NIH, Bldg 2DEM,Room 655,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM EverhartJ@extra.niddk.nih.gov
NR 21
TC 16
Z9 17
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2010
VL 51
IS 5
BP 1491
EP 1493
DI 10.1002/hep.23659
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 590XJ
UT WOS:000277261400005
PM 20432252
ER
PT J
AU Kuniholm, MH
Kovacs, A
Gao, XJ
Xue, XN
Marti, D
Thio, CL
Peters, MG
Terrault, NA
Greenblatt, RM
Goedert, JJ
Cohen, MH
Minkoff, H
Gange, SJ
Anastos, K
Fazzari, M
Harris, TG
Young, MA
Strickler, HD
Carrington, M
AF Kuniholm, Mark H.
Kovacs, Andrea
Gao, Xiaojiang
Xue, Xiaonan
Marti, Darlene
Thio, Chloe L.
Peters, Marion G.
Terrault, Norah A.
Greenblatt, Ruth M.
Goedert, James J.
Cohen, Mardge H.
Minkoff, Howard
Gange, Stephen J.
Anastos, Kathryn
Fazzari, Melissa
Harris, Tiffany G.
Young, Mary A.
Strickler, Howard D.
Carrington, Mary
TI Specific Human Leukocyte Antigen Class I and II Alleles Associated with
Hepatitis C Virus Viremia
SO HEPATOLOGY
LA English
DT Article
ID SPONTANEOUS VIRAL CLEARANCE; INHIBITORY RECEPTOR GENES; INJECTION-DRUG
USERS; T-CELL RESPONSES; MHC CLASS-I; RHEUMATOID-ARTHRITIS; HUMAN
IMMUNODEFICIENCY; AUTOIMMUNE HEPATITIS; INFECTED PATIENTS;
IMMUNE-RESPONSES
AB Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010;51: 1514-1522.)
C1 [Kuniholm, Mark H.; Xue, Xiaonan; Anastos, Kathryn; Fazzari, Melissa; Harris, Tiffany G.; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Kovacs, Andrea] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA.
[Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Thio, Chloe L.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Peters, Marion G.; Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Cohen, Mardge H.] Cook Cty Bur Hlth Serv, CORE Ctr, Chicago, IL USA.
[Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
[Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
[Carrington, Mary] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA.
RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer Bldg 1308, Bronx, NY 10461 USA.
EM mark.kuniholm@einstein.yu.edu
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590,
5R01A1057006-04]; National Institute of Child Health and Human
Development [UO1-HD-32632]; National Cancer Institute; National
Institute on Drug Abuse; National Institute on Deafness and Other
Communication Disorders; National Center for Research Resources
(UCSF-CTSI) [UL1 RR024131]; NCI, NIH [HHSN261200800001E]; NIH, NCI,
Center for Cancer Research
FX Data in this article were collected by the Women's Interagency HIV Study
(WIHS) Collaborative Study Group with centers (Principal Investigators)
at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY
(Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young);
the Connie Wofsy Study Consortium of Northern California (Ruth
Greenblatt); Los Angeles County/Southern California Consortium
(Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating
Center (Stephen Gang). The WIHS is funded by the National Institute of
Allergy and Infectious Diseases (UO1-A1-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the
National Institute of Child Health and Human Development (UO1-HD-32632).
The study is cofunded by the National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders. Funding is also provided by the National
Center for Research Resources (UCSF-CTSI Grant number UL1 RR024131).
Additional funding for this project was provided by a grant from the
National Institute of Allergy and Infectious Diseases (5R01A1057006-04
to H.D.S.). This project was funded in part with federal funds from the
NCI, NIH, under Contract No, HHSN261200800001E. This research was
supported in part by the Intramural Research Program of the NIH, NCI,
Center for Cancer Research.
NR 60
TC 53
Z9 55
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2010
VL 51
IS 5
BP 1514
EP 1522
DI 10.1002/hep.23515
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 590XJ
UT WOS:000277261400008
PM 20169624
ER
PT J
AU Horiguchi, N
Lafdil, F
Miller, AM
Park, O
Wang, H
Rajesh, M
Mukhopadhyay, P
Fu, XY
Pacher, P
Gao, B
AF Horiguchi, Norio
Lafdil, Fouad
Miller, Andrew M.
Park, Ogyi
Wang, Hua
Rajesh, Mohanraj
Mukhopadhyay, Partha
Fu, Xin Yuan
Pacher, Pal
Gao, Bin
TI Dissociation Between Liver Inflammation and Hepatocellular Damage
Induced by Carbon Tetrachloride in Myeloid Cell-Specific Signal
Transducer and Activator of Transcription 3 Gene Knockout Mice
SO HEPATOLOGY
LA English
DT Article
ID CHRONIC HEPATITIS-C; NORMAL AMINOTRANSFERASE LEVELS; HEPATOCYTE
PROLIFERATION; INJURY; STAT3; FIBROSIS; INTERLEUKIN-6; NEUTROPHILS;
DISEASE; INFECTION
AB Liver injury is associated with inflammation, which is generally believed to accelerate the progression of liver diseases; however, clinical data show that inflammation does not always correlate with hepatocelluar damage in some patients. Investigating the cellular mechanisms underlying these events using an experimental animal model, we show that inflammation may attenuate liver necrosis induced by carbon tetrachloride (CCl(4)) in myeloid-specific signal transducer and activator of transcription 3 (STAT3) knockout mice. As an important anti-inflammatory signal, conditional deletion of STAT3 in myeloid cells results in markedly enhanced liver inflammation after CCl(4) injection. However, these effects are also accompanied by reduced liver necrosis, correlating with elevated serum interleukin-6 (IL-6) and hepatic STAT3 activation. An additional deletion of STAT3 in hepatocytes in myeloid-specific STAT3 knockout mice restored hepatic necrosis but decreased liver inflammation. Conclusion: Inflammation-mediated STAT3 activation attenuates hepatocellular injury induced by CCl(4) in myeloid-specific STAT3 knockout mice, suggesting that inflammation associated with a predominance of hepatoprotective cytokines that activate hepatic STAT3 may reduce rather than accelerate hepatocellular damage in patients with chronic liver diseases. (HEPATOLOGY 2010; 51:1724-1734)
C1 [Horiguchi, Norio; Lafdil, Fouad; Miller, Andrew M.; Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Sect Liver Biol, LPS, NIH, Bethesda, MD 20892 USA.
[Rajesh, Mohanraj; Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, LPS, NIH, Bethesda, MD 20892 USA.
[Fu, Xin Yuan] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
RP Gao, B (reprint author), NIAAA, Sect Liver Biol, LPS, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health (NIH); NIH
FX Supported by the intramural program of National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health (NIH). Dr. Norio
Horiguchi was supported partially by the Japan Society for the Promotion
of Science (ASPS) award at NIH.
NR 34
TC 30
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U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2010
VL 51
IS 5
BP 1724
EP 1734
DI 10.1002/hep.23532
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 590XJ
UT WOS:000277261400030
PM 20196117
ER
PT J
AU Weigert, R
Sramkova, M
Parente, L
Amornphimoltham, P
Masedunskas, A
AF Weigert, Roberto
Sramkova, Monika
Parente, Laura
Amornphimoltham, Panomwat
Masedunskas, Andrius
TI Intravital microscopy: a novel tool to study cell biology in living
animals
SO HISTOCHEMISTRY AND CELL BIOLOGY
LA English
DT Review
DE Intravital microscopy; Non-linear microscopy; Live animal imaging;
Membrane traffic; Two-photon microscopy
ID RAMAN SCATTERING MICROSCOPY; EXCITATION FLUORESCENCE MICROSCOPY;
IN-VIVO; 2-PHOTON MICROSCOPY; MULTIPHOTON MICROSCOPY; DENDRITIC CELLS;
LYMPH-NODES; 2ND-HARMONIC GENERATION; SKELETAL-MUSCLE; QUANTUM DOTS
AB Intravital microscopy encompasses various optical microscopy techniques aimed at visualizing biological processes in live animals. In the last decade, the development of non-linear optical microscopy resulted in an enormous increase of in vivo studies, which have addressed key biological questions in fields such as neurobiology, immunology and tumor biology. Recently, few studies have shown that subcellular processes can be imaged dynamically in the live animal at a resolution comparable to that achieved in cell cultures, providing new opportunities to study cell biology under physiological conditions. The overall aim of this review is to give the reader a general idea of the potential applications of intravital microscopy with a particular emphasis on subcellular imaging. An overview of some of the most exciting studies in this field will be presented using resolution as a main organizing criterion. Indeed, first we will focus on those studies in which organs were imaged at the tissue level, then on those focusing on single cells imaging, and finally on those imaging subcellular organelles and structures.
C1 [Weigert, Roberto; Sramkova, Monika; Parente, Laura; Amornphimoltham, Panomwat; Masedunskas, Andrius] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficing Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficing Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr Room 303A, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU 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
apologize to those whose work could not be cited due to space
limitations. We would like to thank Dr. Silvio Gutkind, Dr. Julie
Donaldson and Dr. Omayma Al-Awar for critical reading of the manuscript
and all the members of the Oral and Pharyngeal Cancer Branch for
invaluable assistance.
NR 122
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U2 25
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 MAY
PY 2010
VL 133
IS 5
BP 481
EP 491
DI 10.1007/s00418-010-0692-z
PG 11
WC Cell Biology; Microscopy
SC Cell Biology; Microscopy
GA 581KG
UT WOS:000276520700001
PM 20372919
ER
PT J
AU Kuo, YM
Li, ZS
Jiao, Y
Gaborit, N
Pani, AK
Orrison, BM
Bruneau, BG
Giasson, BI
Smeyne, RJ
Gershon, MD
Nussbaum, RL
AF Kuo, Yien-Ming
Li, Zhishan
Jiao, Yun
Gaborit, Nathalie
Pani, Amar K.
Orrison, Bonnie M.
Bruneau, Benoit G.
Giasson, Benoit I.
Smeyne, Richard J.
Gershon, Michael D.
Nussbaum, Robert L.
TI Extensive enteric nervous system abnormalities in mice transgenic for
artificial chromosomes containing Parkinson disease-associated
alpha-synuclein gene mutations precede central nervous system changes
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HEART-RATE-VARIABILITY; LEWY BODIES; DOPAMINERGIC-NEURONS;
GASTROINTESTINAL DYSFUNCTION; INTESTINAL MOTILITY; BRAIN PATHOLOGY;
COLONIC TRANSIT; RODENT MODELS; WILD-TYPE; CONSTIPATION
AB Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant alpha-synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target alpha-synuclein toxicity at its earliest stages.
C1 [Kuo, Yien-Ming; Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Li, Zhishan; Gershon, Michael D.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Jiao, Yun; Pani, Amar K.; Smeyne, Richard J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Gaborit, Nathalie; Bruneau, Benoit G.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
[Orrison, Bonnie M.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Giasson, Benoit I.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Dept Med, Box 0794,513 Parnassus Ave, San Francisco, CA 94143 USA.
EM nussbaumr@humgen.ucsf.edu
RI Gaborit, Nathalie/D-4977-2015;
OI Bruneau, Benoit/0000-0002-0804-7597
FU Division of Intramural Research, National Human Genome Research
Institute (NIH); Michael J. Fox Foundation; UCSF Department of Medicine
and Institute of Human Genetics; National Institutes of Health
[NS053488, NS12969, NS15547]; American Lebanese Syrian Associated
Charities
FX Supported by the Division of Intramural Research, National Human Genome
Research Institute (NIH), a grant from the Michael J. Fox Foundation,
and institutional funding from the UCSF Department of Medicine and
Institute of Human Genetics (R. L. N.), National Institutes of Health
(grant number NS053488) (B. G.), American Lebanese Syrian Associated
Charities (R. S.) and National Institutes of Health (grant numbers
NS12969 and NS15547) (M. G.).
NR 76
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U1 4
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2010
VL 19
IS 9
BP 1633
EP 1650
DI 10.1093/hmg/ddq038
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581MF
UT WOS:000276526700001
PM 20106867
ER
PT J
AU Nelson, GW
Freedman, BI
Bowden, DW
Langefeld, CD
An, P
Hicks, PJ
Bostrom, MA
Johnson, RC
Kopp, JB
Winkler, CA
AF Nelson, George W.
Freedman, Barry I.
Bowden, Donald W.
Langefeld, Carl D.
An, Ping
Hicks, Pamela J.
Bostrom, Meredith A.
Johnson, Randall C.
Kopp, Jeffrey B.
Winkler, Cheryl A.
TI Dense mapping of MYH9 localizes the strongest kidney disease
associations to the region of introns 13 to 15
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID 9 GENE MYH9; TYPE-2 DIABETES-MELLITUS; STAGE RENAL-DISEASE;
AFRICAN-AMERICANS; HAPLOTYPE MAP; HUMAN GENOME; POLYMORPHISMS;
HYPERTENSION; ALBUMINURIA
AB Admixture mapping recently identified MYH9 as a susceptibility gene for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN) and end-stage kidney disease attributed to hypertension (H-ESKD) in African Americans (AA). MYH9 encodes the heavy chain of non-muscle myosin IIA, a cellular motor involved in motility. A haplotype and its tagging SNPs spanning introns 12-23 were most strongly associated with kidney disease (OR 2-7; P < 10(-8), recessive). To narrow the region of association and identify potential causal variation, we performed a dense-mapping study using 79 MYH9 SNPs in AA populations with FSGS, HIVAN and H-ESKD (typed for a subset of 46 SNPs), for a total of 2496 cases and controls. The strongest associations were for correlated SNPs rs5750250, rs2413396 and rs5750248 in introns 13, 14 and 15, a region of 5.6 kb. Rs5750250 showed OR 5.0, 8.0 and 2.8; P = 2 x 10(-17), 2 x 10(-10) and 3 x 10(-22), respectively, for FSGS, HIVAN and H-ESKD; OR 5.7; P = 9 x 10(-27) for combined FSGS and HIVAN, recessive. An independent association was observed for rs11912763 in intron 33. Neither the highly associated SNPs nor the results of resequencing MYH9 in 40 HIVAN or FSGS cases and controls revealed non-synonymous changes that could account for the disease associations. Rs2413396 and one of the highly associated SNPs in intron 23, rs4821480, are predicted splicing motif modifiers. Rs5750250 combined with rs11912763 had receiver operator characteristic (ROC) C statistics of 0.80, 0.73 and 0.65 for HIVAN, FSGS and H-ESKD, respectively, allowing prediction of genetic risk by typing two SNPs.
C1 [Nelson, George W.; An, Ping; Johnson, Randall C.; Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Freedman, Barry I.; Bowden, Donald W.; Langefeld, Carl D.; Hicks, Pamela J.; Bostrom, Meredith A.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Winkler, CA (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Bldg 560, Frederick, MD 21701 USA.
EM winklerc@mail.nih.gov
RI Johnson, Randall/B-1517-2014;
OI Johnson, Randall/0000-0001-7754-0847; Kopp, Jeffrey/0000-0001-9052-186X
FU National Cancer Institute, National Institutes of Health [N01-CO-12400,
HHSN261200800001E]; National Cancer Institute, Center for Cancer
Research [ZIA BC 010022]; National Institute for Diabetes, Digestive and
Kidney Diseases [ZO-1 DK043308, RO1 DK070941, DK084149]
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 number N01-CO-12400 and HHSN261200800001E. This research was
supported in part by the Intramural Research Program of National Cancer
Institute, Center for Cancer Research (Project ZIA BC 010022).
Additional funding was provided by the National Institute for Diabetes,
Digestive and Kidney Diseases (Project ZO-1 DK043308, to J.B.K.), as
well as well as by grants RO1 DK070941 and DK084149 (to B. I. F.).
Funding to pay the Open Access publication charges for this article was
provided by Project ZIA BC 010022.
NR 24
TC 38
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2010
VL 19
IS 9
BP 1805
EP 1815
DI 10.1093/hmg/ddq039
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581MF
UT WOS:000276526700014
PM 20124285
ER
PT J
AU Behar, DM
Rosset, S
Tzur, S
Selig, S
Yudkovsky, G
Bercovici, S
Kopp, JB
Winkler, CA
Nelson, GW
Wasser, WG
Skorecki, K
AF Behar, Doron M.
Rosset, Saharon
Tzur, Shay
Selig, Sara
Yudkovsky, Guennady
Bercovici, Sivan
Kopp, Jeffrey B.
Winkler, Cheryl A.
Nelson, George W.
Wasser, Walter G.
Skorecki, Karl
TI African ancestry allelic variation at the MYH9 gene contributes to
increased susceptibility to non-diabetic end-stage kidney disease in
Hispanic Americans
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-ASSOCIATED NEPHROPATHY;
RENAL-DISEASE; GLOMERULAR PROTEIN; ADMIXTURE DYNAMICS; NEPHROTIC
SYNDROME; POPULATIONS; POLYMORPHISMS; MUTATIONS; LINKAGE
AB Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.
C1 [Behar, Doron M.; Selig, Sara; Skorecki, Karl] Mol Med Lab, IL-31096 Haifa, Israel.
[Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Skorecki, Karl] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med & Res Inst, IL-31096 Haifa, Israel.
[Rosset, Saharon] Tel Aviv Univ, Dept Stat & Operat Res, IL-69978 Tel Aviv, Israel.
[Bercovici, Sivan] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
[Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Winkler, Cheryl A.; Nelson, George W.] NIH, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA.
[Wasser, Walter G.] Cabrini Med Ctr, New York, NY USA.
RP Skorecki, K (reprint author), 8 Haaliyah St, IL-31096 Haifa, Israel.
EM skorecki@tx.technion.ac.il
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Canadian and American Technion Societies; Israel Science Foundation
[890015, 1227/09]; Legacy Heritage Fund; European Research Commission
[MIRG-CT-2007-208019]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; National Cancer Institute, Center for Cancer
Research; National Institute for Diabetes, Digestive and Kidney Diseases
[ZO-1 DK043308]
FX This work was supported by the Canadian and American Technion Societies
(Eshagian Estate Fund, Veronique Elek Fund, Dr Sidney Kremer Kidney
Disease Research Fund); the Israel Science Foundation (890015), and
Legacy Heritage Fund; to K. S. The European Research Commission
(MIRG-CT-2007-208019); and the Israel Science Foundation (1227/09); to
S. R. The National Cancer Institute, National Institutes of Health
(HHSN261200800001E); the Intramural Research Program of National Cancer
Institute, Center for Cancer Research (the content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the US Government); and
the National Institute for Diabetes, Digestive and Kidney Diseases
(Project ZO-1 DK043308), to J.B.K.
NR 36
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U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2010
VL 19
IS 9
BP 1816
EP 1827
DI 10.1093/hmg/ddq040
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581MF
UT WOS:000276526700015
PM 20144966
ER
PT J
AU Barbalic, M
Dupuis, J
Dehghan, A
Bis, JC
Hoogeveen, RC
Schnabel, RB
Nambi, V
Bretler, M
Smith, NL
Peters, A
Lu, C
Tracy, RP
Aleksic, N
Heeriga, J
Keaney, JF
Rice, K
Lip, GYH
Vasan, RS
Glazer, NL
Larson, MG
Uitterlinden, AG
Yamamoto, J
Durda, P
Haritunians, T
Psaty, BM
Boerwinkle, E
Hofman, A
Koenig, W
Jenny, NS
Witteman, JC
Ballantyne, C
Benjamin, EJ
AF Barbalic, Maja
Dupuis, Josee
Dehghan, Abbas
Bis, Joshua C.
Hoogeveen, Ron C.
Schnabel, Renate B.
Nambi, Vijay
Bretler, Monique
Smith, Nicholas L.
Peters, Annette
Lu, Chen
Tracy, Russell P.
Aleksic, Nena
Heeriga, Jan
Keaney, John F., Jr.
Rice, Kenneth
Lip, Gregory Y. H.
Vasan, Ramachandran S.
Glazer, Nicole L.
Larson, Martin G.
Uitterlinden, Andre G.
Yamamoto, Jennifer
Durda, Peter
Haritunians, Talin
Psaty, Bruce M.
Boerwinkle, Eric
Hofman, Albert
Koenig, Wolfgang
Jenny, Nancy S.
Witteman, Jacqueline C.
Ballantyne, Christie
Benjamin, Emelia J.
TI Large-scale genomic studies reveal central role of ABO in sP-selectin
and sICAM-1 levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID INTERCELLULAR-ADHESION MOLECULE-1; HUMAN-ENDOTHELIAL-CELLS; SOLUBLE
P-SELECTIN; PLASMODIUM-FALCIPARUM MALARIA; CORONARY-ARTERY-DISEASE;
VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; BLOOD-GROUP;
CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK
AB P-selectin and intercellular adhesion molecule-1 (ICAM-1) participate in inflammatory processes by promoting adhesion of leukocytes to vascular wall endothelium. Their soluble levels have been associated with adverse cardiovascular events. To identify loci affecting soluble levels of P-selectin (sP-selectin) and ICAM-1 (sICAM-1), we performed a genome-wide association study in a sample of 4115 (sP-selectin) and 9813 (sICAM-1) individuals of European ancestry as a part of The Cohorts for Heart and Aging Research in Genome Epidemiology consortium. The most significant SNP association for sP-selectin was within the SELP gene (rs6136, P = 4.05 x 10(-61)) and for sICAM-1 levels within the ICAM-1 gene (rs3093030, P = 3.53 x 10(-23)). Both sP-selectin and sICAM-1 were associated with ABO gene variants (rs579459, P = 1.86 x 10(-41) and rs649129, P = 1.22 x 10(-15), respectively) and in both cases the observed associations could be accounted for by the A1 allele of the ABO blood group. The absence of an association between ABO blood group and platelet-bound P-selectin levels in an independent subsample (N = 1088) from the ARIC study, suggests that the ABO blood group may influence cleavage of the P-selectin protein from the cell surface or clearance from the circulation, rather than its production and cellular presentation. These results provide new insights into adhesion molecule biology.
C1 [Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Dupuis, Josee; Schnabel, Renate B.; Keaney, John F., Jr.; Vasan, Ramachandran S.; Larson, Martin G.; Yamamoto, Jennifer; Benjamin, Emelia J.] Boston Univ, NHLBI, Framingham Heart Study, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Unvivers, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Dupuis, Josee; Lu, Chen] Boston Unvivers, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dehghan, Abbas; Bretler, Monique; Heeriga, Jan; Hofman, Albert; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Bis, Joshua C.; Glazer, Nicole L.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Hlth Serv, Seattle, WA 98195 USA.
[Hoogeveen, Ron C.; Nambi, Vijay; Aleksic, Nena; Ballantyne, Christie] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Hoogeveen, Ron C.; Nambi, Vijay; Aleksic, Nena; Ballantyne, Christie] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Munich, Germany.
[Tracy, Russell P.; Durda, Peter; Jenny, Nancy S.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
[Lip, Gregory Y. H.] City Hosp, Univ Dept Med, Haemostasis Thrombosis & Vasc Biol Unit, Birmingham, W Midlands, England.
[Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
RP Barbalic, M (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Herman Pressler, Houston, TX USA.
EM maja.barbalic@uth.tmc.edu
RI Rice, Kenneth/A-4150-2013; Schnabel, Renate/F-6527-2014; Peters,
Annette/A-6117-2011; Lu, Chen/D-8514-2015;
OI Rice, Kenneth/0000-0001-5779-4495; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970; Dupuis,
Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336;
Dehghan, Abbas/0000-0001-6403-016X
FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367, R01HL086694, N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01 HL087652]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C,
UL1RR025005]
FX ARIC: The Atherosclerosis Risk in Communities 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-HC55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367 and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research. CHS: The
research reported in this article was supported by contract numbers
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 and R01
HL087652 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. Genotyping was supported by the Cedars-Sinai
General Clinical Research Center grant M01-RR00425 and NIDDK grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. A full list of principal CHS investigators and institutions can
be found at http://www. chs-nhlbi. org/pi. htm. FHS: This research was
conducted in part using data and resources from the Framingham Heart
Study of the National Heart Lung and Blood Institute of the National
Institutes of Health and Boston University School of Medicine. The
analyses reflect intellectual input and resource development from the
Framingham Heart Study investigators participating in the SNP Health
Association Resource (SHARe) project. This work was partially supported
by the National Heart, Lung and Blood Institute's Framingham Heart Study
(Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for
genotyping services (Contract No. N02-HL-6-4278). A portion of this
research utilized the Linux Cluster for Genetic Analysis (LinGA-II)
funded by the Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center. The work was also supported in part by grants from the National
Institutes of Health HL076784, AG028321 and HL064753 to Dr Benjamin. RS:
The Rotterdam Study is supported by the Erasmus Medical Center and
Erasmus University Rotterdam; the Netherlands Organization for
Scientific Research; the Netherlands Organization for Health Research
and Development (ZonMw); the Research Institute for Diseases in the
Elderly; The Netherlands Heart Foundation; the Ministry of Education,
Culture and Science; the Ministry of Health Welfare and Sports; the
European Commission; and the Municipality of Rotterdam. Support for
genotyping was provided by the Netherlands Organization for Scientific
Research (NWO) (175.010.2005.011, 911.03.012) and Research Institute for
Diseases in the Elderly (RIDE). This study was further supported by the
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) project nr. 050-060-810.
NR 60
TC 94
Z9 98
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2010
VL 19
IS 9
BP 1863
EP 1872
DI 10.1093/hmg/ddq061
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581MF
UT WOS:000276526700020
PM 20167578
ER
PT J
AU Entezam, A
Lokanga, AR
Le, W
Hoffman, G
Usdin, K
AF Entezam, Ali
Lokanga, Adihe Rachel
Le, Wei
Hoffman, Gloria
Usdin, Karen
TI Potassium Bromate, a Potent DNA Oxidizing Agent, Exacerbates Germline
Repeat Expansion in a Fragile X Premutation Mouse Model
SO HUMAN MUTATION
LA English
DT Article
DE repeat expansion disease; triplet repeat instability; Fragile X
syndrome; FMR1; DNA repair; oxidative damage; 7; 8-dihydro-8-oxo-guanine
(8-oxoG)
ID MYOTONIC-DYSTROPHY TYPE-1; CAG TRIPLET REPEATS; ESCHERICHIA-COLI;
SACCHAROMYCES-CEREVISIAE; TRINUCLEOTIDE REPEATS; MISMATCH REPAIR;
GENETIC INSTABILITY; FLAP ENDONUCLEASE; DEPENDENT MANNER; OXIDATIVE
STRESS
AB Tandem repeat expansion is responsible for the Repeat Expansion Diseases, a group of human genetic disorders that includes Fragile X syndrome (FXS). FXS results from expansion of a premutation (PM) allele having 55-200 CGG.CCG-repeats in the 5' UTR of the FMR1 gene. The mechanism of expansion is unknown. We have treated FX PM mice with potassium bromate (KBrO(3)), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO(3) increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans. Hum Mutat 31:611-616, 2010. Published 2010 Wiley-Liss, Inc.
C1 [Entezam, Ali; Lokanga, Adihe Rachel; Usdin, Karen] Natl Inst Diabet Digest & Kidney Dis, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
[Entezam, Ali] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
[Le, Wei; Hoffman, Gloria] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA.
RP Usdin, K (reprint author), Natl Inst Diabet Digest & Kidney Dis, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,K Room 202,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
FU NIDDK (NIH); Eunice Kennedy Shriver NICHD (NIH) [1U54 HD 36207]
FX We thank Dr. Debbie Hinton for her reading of our manuscript and the
great NIDDK animal care staff that made this work possible. This
research was supported by the Intramural Program of the NIDDK (NIH) and
the extramural program of the Eunice Kennedy Shriver NICHD (NIH) through
cooperative agreement 1U54 HD 36207 as part of the Specialized
Cooperative Centers Program in Reproduction and Infertility Research.
NR 59
TC 31
Z9 33
U1 1
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD MAY
PY 2010
VL 31
IS 5
BP 611
EP 616
DI 10.1002/humu.21237
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 597RT
UT WOS:000277779100012
PM 20213777
ER
PT J
AU Karumanchi, SA
Levine, RJ
AF Karumanchi, S. Ananth
Levine, Richard J.
TI How Does Smoking Reduce the Risk of Preeclampsia?
SO HYPERTENSION
LA English
DT Editorial Material
ID HEME OXYGENASE-1; SOLUBLE ENDOGLIN; CARBON-MONOXIDE; PREGNANCY;
OUTCOMES; WOMEN
C1 [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Howard Hughes Med Inst, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Howard Hughes Med Inst, 330 Brookline Ave,RN 370D, Boston, MA 02215 USA.
EM sananth@bidmc.harvard.edu; levinerj@mail.nih.gov
FU Howard Hughes Medical Institute
NR 14
TC 23
Z9 23
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2010
VL 55
IS 5
BP 1100
EP 1101
DI 10.1161/HYPERTENSIONAHA.109.148973
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 583KA
UT WOS:000276672500009
PM 20231524
ER
PT J
AU Huang, XR
Chung, ACK
Yang, FY
Yue, WS
Deng, CX
Lau, CP
Tse, HF
Lan, HY
AF Huang, Xiao R.
Chung, Arthur C. K.
Yang, Fuye
Yue, Wensheng
Deng, Chuxia
Lau, Chu Pak
Tse, Hung Fat
Lan, Hui Y.
TI Smad3 Mediates Cardiac Inflammation and Fibrosis in Angiotensin
II-Induced Hypertensive Cardiac Remodeling
SO HYPERTENSION
LA English
DT Article
DE hypertension; cardiac remodeling; TGF-beta; Smad3; angiotensin II
ID SMOOTH-MUSCLE-CELLS; TGF-BETA; MYOCARDIAL FIBROSIS; FAILING HEART;
EXPRESSION; CONTRIBUTES; DISRUPTION; MECHANISM; PATHWAY; SYSTEM
AB Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-beta/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin 11 infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P<0.05), an increase in left ventricular mass (P<0.05), and the development of cardiac fibrosis and inflammation, including upregulation of transforming growth factor-beta 1, connective tissue growth factor, collagen 1/111, alpha-smooth muscle actin, interleukin 1 beta, tumor necrosis factor-alpha, monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and an increase in macrophage and T-celi infiltration in left, ventricular tissues (all P<0.01, respectively). Additional studies in vitro also revealed that angiotensin II induced cardiac fibrosis and inflammation were prevented in Smad3 KO cardiac fibroblasts. Inactivation of both Smad3 and nuclear factor KB/p65 signaling pathways was a key mechanism by which Sinad3 KO mice were protected from angiotensin II mediated hypertensive cardiac remodeling. In conclusion, Smad3 plays an essential role in hypertensive cardiac remodeling. Results from this study suggest that targeting Smad3 may be a novel therapeutic strategy for hypertensive cardiovascular disease. (Hypertension. 2010;55:1165-1171.)
C1 [Huang, Xiao R.; Chung, Arthur C. K.; Lan, Hui Y.] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
[Huang, Xiao R.; Chung, Arthur C. K.; Lan, Hui Y.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China.
[Yang, Fuye; Yue, Wensheng; Lau, Chu Pak; Tse, Hung Fat] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Deng, Chuxia] NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD USA.
RP Lan, HY (reprint author), Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
EM hylan@cuhk.edu.hk
RI Hossain, Sarah /C-7332-2009; deng, chuxia/N-6713-2016; Lan,
hui/C-9734-2015
OI Hossain, Sarah /0000-0003-1355-0979; Lan, hui/0000-0003-4283-9755
NR 34
TC 62
Z9 64
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 MAY
PY 2010
VL 55
IS 5
BP 1165
EP U153
DI 10.1161/HYPERTENSIONAHA.109.147611
PG 14
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 583KA
UT WOS:000276672500019
PM 20231525
ER
PT J
AU Petrak, O
Strauch, B
Zelinka, T
Rosa, J
Holaj, R
Vrankova, A
Kasalicky, M
Kvasnicka, J
Pacak, K
Widimsky, J
AF Petrak, Ondrej
Strauch, Branislav
Zelinka, Tomas
Rosa, Jan
Holaj, Robert
Vrankova, Alice
Kasalicky, Mojmir
Kvasnicka, Jan
Pacak, Karel
Widimsky, Jiri, Jr.
TI Factors influencing arterial stiffness in pheochromocytoma and effect of
adrenalectomy
SO HYPERTENSION RESEARCH
LA English
DT Article
DE arterial stiffness; catecholamines; pheochromocytoma; pulse wave
velocity
ID PULSE-WAVE VELOCITY; BLOOD-PRESSURE VARIABILITY; ESSENTIAL-HYPERTENSION;
INDEPENDENT PREDICTOR; AORTIC STIFFNESS; CARDIOVASCULAR MORTALITY;
ALPHA-ADRENOCEPTOR; INTIMA-MEDIA; INFLAMMATION; MECHANISMS
AB The aim of the study was to evaluate arterial stiffness and its modulating factors measured by carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI) in patients with pheochromocytoma (PHEO) before and after surgery. Forty-five patients with PHEO and 45 healthy controls were investigated using an applanation tonometer (SphygmoCor, AtCor Medical). The gender, age, BMI and lipid profiles were comparable among both groups. The main difference in basic characteristic was as expected for fasting plasma glucose (P < 0.001) and all blood pressure modalities. PWV in PHEO was significantly higher than in controls (7.2 +/- 1.4 vs. 5.8 +/- 0.5 ms(-1); P < 0.001). Between-group difference in PWV remained significant even after the adjustment for age, heart rate, fasting plasma glucose and each of brachial (P < 0.001) and 24 h blood pressure parameters (P < 0.01). The difference in AI between groups did not reach the statistical significance (19 +/- 14 vs. 16 +/- 13%; NS). In multiple regression analysis, age (P < 0.001), mean blood pressure (P = 0.002), high-sensitive C-reactive protein (hs-CRP) (P = 0.007) and 24 h urine norepinephrine (P = 0.007) were independently associated with PWV in PHEO. In addition, 27 patients with PHEO were studied 1 year after tumor removal. Successful tumor removal led to a significant decrease in PWV (7.0 +/- 1.2 vs. 6.0 +/- 1.1 ms(-1); P < 0.001). In conclusion, patients with PHEO have an increase in PWV, which is reversed by the successful tumor removal. Age, mean blood pressure, hs-CRP and norepinephrine levels are independent predictors of PWV. Hypertension Research (2010) 33, 454-459; doi: 10.1038/hr.2010.12; published online 26 February 2010
C1 [Petrak, Ondrej; Strauch, Branislav; Zelinka, Tomas; Rosa, Jan; Holaj, Robert; Vrankova, Alice; Widimsky, Jiri, Jr.] Charles Univ Prague, Gen Fac Hosp, Fac Med 1, Dept Med 3, Prague 12808 2, Czech Republic.
[Kasalicky, Mojmir] Charles Univ Prague, Gen Fac Hosp, Fac Med 1, Dept Surg, Prague 12808 2, Czech Republic.
[Kvasnicka, Jan] Charles Univ Prague, Gen Fac Hosp, Fac Med 1, Cent Hematol Lab, Prague 12808 2, Czech Republic.
[Pacak, Karel] NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA.
RP Petrak, O (reprint author), Charles Univ Prague, Gen Fac Hosp, Fac Med 1, Dept Med 3, U Nemocnice 1, Prague 12808 2, Czech Republic.
EM Ondrej.Petrak@vfn.cz
RI Petrak, Ondrej/A-5839-2017; Vrankova, Alice/C-2516-2017; Holaj,
Robert/D-4241-2017; Zelinka, Tomas/D-4276-2017; Strauch,
Branislab/D-4274-2017
OI Petrak, Ondrej/0000-0001-8992-3562; Vrankova, Alice/0000-0002-2327-2338;
Holaj, Robert/0000-0002-9488-9706; Zelinka, Tomas/0000-0003-3395-8373;
Strauch, Branislab/0000-0001-5137-7017
FU Ministry of Education, Czech Republic [MSM-0021620807, MSM-0021620817,
MSM-0021620808]; Ministry of Health, Czech Republic [MZOVFN2005, IGA
NT/11291-5]
FX We highly appreciate the statistical help of Dr D Wichterle and
technical assistance of Mrs L Landova. This study was supported by the
Research Projects MSM-0021620807, MSM-0021620817 and MSM-0021620808 of
The Ministry of Education, Czech Republic, Research Project MZOVFN2005
and IGA NT/11291-5 of the Ministry of Health, Czech Republic.
NR 45
TC 8
Z9 8
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0916-9636
J9 HYPERTENS RES
JI Hypertens. Res.
PD MAY
PY 2010
VL 33
IS 5
BP 454
EP 459
DI 10.1038/hr.2010.12
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 591VT
UT WOS:000277333900012
PM 20186147
ER
PT J
AU Yan, PK
Xu, S
Turkbey, B
Kruecker, J
AF Yan, Pingkun
Xu, Sheng
Turkbey, Baris
Kruecker, Jochen
TI Discrete Deformable Model Guided by Partial Active Shape Model for TRUS
Image Segmentation
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Discrete deformable model (DDM); dynamic programming; image
segmentation; partial active shape model (PASM); prostate; transrectal
ultrasound (TRUS)
ID PROSTATE BOUNDARY SEGMENTATION; PRINCIPAL COMPONENT ANALYSIS; 2D
ULTRASOUND IMAGES
AB Automatic prostate segmentation in transrectal ultrasound (TRUS) images is highly desired in many clinical applications. However, robust and automated prostate segmentation is challenging due to the low SNR in TRUS and the missing boundaries in shadow areas caused by calcifications or hyperdense prostate tissues. This paper presents a novel method of utilizing a priori shapes estimated from partial contours for segmenting the prostate. The proposed method is able to automatically extract prostate boundary from 2-D TRUS images without user interaction for shape correction in shadow areas. During the segmentation process, missing boundaries in shadow areas are estimated by using a partial active shape model, which takes partial contours as input but returns a complete shape estimation. With this shape guidance, an optimal search is performed by a discrete deformable model to minimize an energy functional for image segmentation, which is achieved efficiently by using dynamic programming. The segmentation of an image is executed in a multiresolution fashion from coarse to fine for robustness and computational efficiency. Promising segmentation results were demonstrated on 301 TRUS images grabbed from 19 patients with the average mean absolute distance error of 2.01 mm +/- 1.02 mm.
C1 [Yan, Pingkun; Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY 10510 USA.
[Turkbey, Baris] NCI, NIH, Bethesda, MD 20892 USA.
RP Yan, PK (reprint author), Philips Res N Amer, Briarcliff Manor, NY 10510 USA.
EM pingkun.yan@philips.com; sheng.xu@philips.com; turkbeyi@mail.nih.gov;
jochen.kruecker@philips.com
NR 29
TC 46
Z9 48
U1 0
U2 6
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD MAY
PY 2010
VL 57
IS 5
BP 1158
EP 1166
DI 10.1109/TBME.2009.2037491
PG 9
WC Engineering, Biomedical
SC Engineering
GA 585GX
UT WOS:000276814200019
PM 20142158
ER
PT J
AU Dustin, ML
Long, EO
AF Dustin, Michael L.
Long, Eric O.
TI Cytotoxic immunological synapses
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE activation; cytotoxicity; synapse; actin; microscopy; adhesion
ID NATURAL-KILLER-CELLS; MHC CLASS-I; SUPRAMOLECULAR ACTIVATION CLUSTERS;
IMMUNOGLOBULIN-LIKE RECEPTOR; RESTING NK CELLS; KINASE-C-THETA; T-CELL;
IMMUNE SYNAPSES; INHIBITORY RECEPTORS; TARGET-CELLS
AB One of the most fundamental activities of the adaptive immune system is to kill infected cells and tumor cells. Two distinct pathways mediate this process, both of which are facilitated by a cytotoxic immunological synapse. While traditionally thought of as innate immune cells, natural killer (NK) cells are now appreciated to have the capacity for long-term adaptation to chemical and viral insults. These cells integrate multiple positive and negative signals through NK cell cytotoxic or inhibitory synapses. The traditional CD8+alpha beta T-cell receptor-positive cells are among the best models for the concept of an immunological synapse, in which vectoral signaling is linked to directed secretion in a stable interface to induce apoptotic cell death in an infected cell. Large-scale molecular organization in synapses generated a number of hypotheses. Studies in the past 5 years have started to provide clear answers regarding the validity of these models. In vivo imaging approaches have provided some hints as to the physiologic relevance of these processes with great promise for the future. This review provides an overview of work on cytotoxic immunological synapses and suggests pathways forward in applying this information to the development of therapeutic agents.
C1 [Dustin, Michael L.] NYU, Sch Med, Skirball Inst Biomol Med, Martin Kimmel Ctr Biol & Med, New York, NY 10016 USA.
[Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Dustin, ML (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, Helen & Martin Kimmel Ctr Biol & Med, 550 1st Ave, New York, NY 10016 USA.
EM michael.dustin@med.nyu.edu
RI Long, Eric/G-5475-2011;
OI Long, Eric/0000-0002-7793-3728; Dustin, Michael/0000-0003-4983-6389
FU NIH [PN2 EY016586, R01 AI052812]; Intramural Research Program of the NIH
FX This study was supported by NIH grants PN2 EY016586 (M.L.D.), R01
AI052812 (M.L.D.) and the Intramural Research Program of the NIH, NIAID
(E.O.L.).
NR 113
TC 71
Z9 71
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAY
PY 2010
VL 235
BP 24
EP 34
PG 11
WC Immunology
SC Immunology
GA 591FO
UT WOS:000277285400003
PM 20536553
ER
PT J
AU Pollard, HB
Levine, MA
Eidelman, O
Pollard, M
AF Pollard, Harvey B.
Levine, Mark A.
Eidelman, Ofer
Pollard, Morris
TI Pharmacological Ascorbic Acid Suppresses Syngeneic Tumor Growth and
Metastases in Hormone-refractory Prostate Cancer
SO IN VIVO
LA English
DT Article
DE Ascorbic acid; metastases; tumor; syngeneic; prostate
ID LOBUND-WISTAR RATS; HYDROGEN-PEROXIDE; EXTENDS SURVIVAL; ADENOCARCINOMA;
CELLS; MODEL
AB Aim: The aim of this study was to test for the influence of ascorbic acid on tumorigenicity and metastases of implanted PAIII prostate cancer adenocarcinoma cells in syngeneic LW rats. Materials and Methods: Hormone-refractory prostate cancer PAIII cells were implanted subcutaneously into immunologically intact, Lobund-Wistar (LW) rats. Intraperitoneal pharmacological doses of ascorbic acid were administered each day for the ensuing 30 days. On the 40th day, animals were sacrificed. Local tumor weights were measured, and metastases were counted. Results: At the end of the 40 day experimental period, the primary tumors were found to be significantly reduced in weight (p=0.026). In addition, sub-pleural lung metastases were even more profoundly reduced in number and size (p=0.009). Grossly enlarged ipsilateral lymph node metastases declined from 7 of 15 rats to 1 of 15 rats. Conclusion: Pharmacological doses of ascorbic acid suppress tumor growth and metastases in hormone-refractory prostate cancer.
C1 [Pollard, Harvey B.; Eidelman, Ofer] USUHS, Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Levine, Mark A.] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA.
[Pollard, Morris] Univ Notre Dame, Lobund Inst, Notre Dame, IN 46556 USA.
RP Pollard, HB (reprint author), USUHS, Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
EM hpollard@usuhs.mil
FU Intramural Research Program, National Institute for Diabetes, Digestive
and Kidney (NIDDK), National Institutes of Health, Bethesda, MD. 20892
[Z01 DK053212-02]; National Cancer Institute, National Institutes of
Health [CA 17559]; National Center for Research Resources, National
Institutes of Health [RR00294]; Coleman Foundation of Chicago;
Retirement Research Foundation of Chicago; Scully Trust; United States
Soyboard; Lobund Institute Endowement; University of Notre Dame
FX This work was supported by: (i) Intramural Research Program, National
Institute for Diabetes, Digestive and Kidney (NIDDK), National
Institutes of Health, Bethesda, MD. 20892, [Z01 DK053212-02] to [MAL];
(ii) National Heart Lung and Blood Institute (NHLBI), National
Institutes of Health: [NO1-HV-28187] to [HBP]: (iii) National Cancer
Institute, National Institutes of Health [CA 17559] and National Center
for Research Resources, National Institutes of Health [RR00294]; The
Coleman Foundation of Chicago; The Retirement Research Foundation of
Chicago; the Scully Trust; the United States Soyboard; Lobund Institute
Endowement; and the University of Notre Dame to [MP]. The authors did
not receive any specific support from private or Institutional bodies
that might have commercial interests in the project.
NR 25
TC 23
Z9 25
U1 0
U2 3
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0258-851X
J9 IN VIVO
JI In Vivo
PD MAY-JUN
PY 2010
VL 24
IS 3
BP 249
EP 255
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 614DL
UT WOS:000279035400001
PM 20554995
ER
PT J
AU Singh, A
Pande, C
Gahtori, P
Pandeya, SN
Stables, JP
AF Singh, Anita
Pande, C.
Gahtori, P.
Pandeya, S. N.
Stables, J. P.
TI Design and Synthesis of Some Novel 4-(4-substituted aryl) Semicarbazones
as Anticonvulsant Agents
SO INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE Anticonvulsant; hydrogen bonding domain; lipophilic aryl/alkyl ring;
4-substituted semicarbazone
ID ANTIEPILEPTIC DRUG
AB In the present study, a series of 4-(4-substituted aryl) semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD) programme NIH, USA using experimental animal, adult male FCM mice (20-25 g) and adult Sprague-Dawley rats (100-150 g) and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity.
C1 [Singh, Anita; Pande, C.; Gahtori, P.] Kumaun Univ, Dept Pharm, Bhimtal 263002, India.
[Pandeya, S. N.] Saroj Inst Pharm, Lucknow 222001, Uttar Pradesh, India.
[Stables, J. P.] Natl Inst Neurol Disorders & Stroke, Epilepsy Branch, NIH, Bethesda, MD 20892 USA.
RP Singh, A (reprint author), Kumaun Univ, Dept Pharm, Bhimtal 263002, India.
EM asingh0501@rediffmail.com
NR 16
TC 2
Z9 4
U1 0
U2 0
PU MEDKNOW PUBLICATIONS
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0250-474X
J9 INDIAN J PHARM SCI
JI Indian J. Pharm. Sci.
PD MAY-JUN
PY 2010
VL 72
IS 3
BP 363
EP U367
DI 10.4103/0250-474X.70485
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 739LS
UT WOS:000288719500015
PM 21188048
ER
PT J
AU Kleba, B
Clark, TR
Lutter, EI
Ellison, DW
Hackstadt, T
AF Kleba, Betsy
Clark, Tina R.
Lutter, Erika I.
Ellison, Damon W.
Hackstadt, Ted
TI Disruption of the Rickettsia rickettsii Sca2 Autotransporter Inhibits
Actin-Based Motility
SO INFECTION AND IMMUNITY
LA English
DT Article
ID SPOTTED-FEVER GROUP; LISTERIA-MONOCYTOGENES; ARP2/3 COMPLEX;
SHIGELLA-FLEXNERI; MONOCLONAL-ANTIBODIES; TRANSPOSON MUTAGENESIS;
DERMACENTOR-ANDERSONI; INTRACELLULAR GROWTH; SURFACE-PROTEINS;
CHICKEN-EMBRYO
AB Rickettsii rickettsii, the etiologic agent of Rocky Mountain spotted fever, replicates within the cytosol of infected cells and uses actin-based motility to spread inter- and intracellularly. Although the ultrastructure of the actin tail and host proteins associated with it are distinct from those of Listeria or Shigella, comparatively little is known regarding the rickettsial proteins involved in its organization. Here, we have used random transposon mutagenesis of R. rickettsii to generate a small-plaque mutant that is defective in actin-based motility and does not spread directly from cell to cell as is characteristic of spotted fever group rickettsiae. The transposon insertion site of this mutant strain was within Sca2, a member of a family of large autotransporter proteins. Sca2 exhibits several features suggestive of its apparent role in actin-based motility. It displays an N-terminal secretory signal peptide, a C-terminal predicted autotransporter domain, up to four predicted Wasp homology 2 (WH2) domains, and two proline-rich domains, one with similarity to eukaryotic formins. In a guinea pig model of infection, the Sca2 mutant did not elicit fever, suggesting that Sca2 and actin-based motility are virulence factors of spotted fever group rickettsiae.
C1 [Kleba, Betsy; Clark, Tina R.; Lutter, Erika I.; Ellison, Damon W.; Hackstadt, Ted] NIAID, Rocky Mt Labs, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM ted_hackstadt@nih.gov
FU NIAID/NIH
FX This work was supported by the Intramural Research Program of NIAID/NIH.
NR 67
TC 60
Z9 61
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2010
VL 78
IS 5
BP 2240
EP 2247
DI 10.1128/IAI.00100-10
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 584UL
UT WOS:000276778700045
PM 20194597
ER
PT J
AU Avril, M
Cartwright, MM
Hathaway, MJ
Hommel, M
Elliott, SR
Williamson, K
Narum, DL
Duffy, PE
Fried, M
Beeson, JG
Smith, JD
AF Avril, Marion
Cartwright, Megan M.
Hathaway, Marianne J.
Hommel, Mirja
Elliott, Salenna R.
Williamson, Kathryn
Narum, David L.
Duffy, Patrick E.
Fried, Michal
Beeson, James G.
Smith, Joseph D.
TI Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly
Cross-Reactive Antibodies to Placental Plasmodium falciparum-Infected
Erythrocytes
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CHONDROITIN-SULFATE-A; PREGNANCY-ASSOCIATED MALARIA; VARIANT
SURFACE-ANTIGENS; CSA-BINDING PARASITES; ADHESION-INHIBITORY ANTIBODIES;
VACCINE CANDIDATE VAR2CSA; MEMBRANE PROTEIN-1; IMMUNOGLOBULIN-G;
STRUCTURAL BASIS; VAR GENE
AB Pregnancy-associated malaria is a severe clinical syndrome associated with the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, a member of the large and diverse P. falciparum erythrocyte membrane 1 (PfEMP1) protein family. To better understand if conserved regions in VAR2CSA can be targeted by antibodies, we immunized rabbits with VAR2CSA-DBL1 and -DBL5 recombinant proteins produced in Pichia pastoris and developed a panel of seven chondroitin sulfate A (CSA)-binding parasites from diverse geographic origins. Overall, no two parasites in the panel expressed the same VAR2CSA sequence. The DBL1 domains averaged 80% amino acid identity (range, 72 to 89%), and the DBL5 domains averaged 86% amino acid identity (range, 83 to 99%), similar to a broader sampling of VAR2CSA sequences from around the world. Whereas antibodies generated against the VAR2CSA-DBL1 recombinant protein had only limited breadth and reacted with three or four parasites in the panel, immunization with DBL5 recombinant proteins elicited broadly cross-reactive antibodies against all or most parasites in the panel, as well as to fresh clinical isolates from pregnant women. These findings demonstrate that the major PfEMP1 variant expressed by placental isolates exposes strain-transcendent epitopes that can be targeted by vaccination and may have application for pregnancy malaria vaccine development.
C1 [Avril, Marion; Cartwright, Megan M.; Hathaway, Marianne J.; Williamson, Kathryn; Duffy, Patrick E.; Fried, Michal; Smith, Joseph D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Hommel, Mirja; Elliott, Salenna R.; Beeson, James G.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[Duffy, Patrick E.; Fried, Michal; Smith, Joseph D.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA.
RP Smith, JD (reprint author), Seattle Biomed Res Inst, 307 Westlake Ave N,Suite 500, Seattle, WA 98109 USA.
EM joe.smith@sbri.org
FU Bill and Melinda Gates Foundation; NIH; Malaria Vaccine Development
Branch; National Institute for Allergy and Infectious Diseases; National
Health and Medical Research Council of Australia
FX This work was supported by a grant from the Bill and Melinda Gates
Foundation (P.E.D., M.F., J.D.S.). This research was supported in part
by the Intramural Research Program of the NIH, Malaria Vaccine
Development Branch, National Institute for Allergy and Infectious
Diseases. J.G.B. and M.H. are supported by the National Health and
Medical Research Council of Australia.
NR 62
TC 24
Z9 24
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2010
VL 78
IS 5
BP 2248
EP 2256
DI 10.1128/IAI.00410-09
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 584UL
UT WOS:000276778700046
PM 20194590
ER
PT J
AU Holmes, EC
AF Holmes, Edward C.
TI Does hepatitis C virus really form quasispecies?
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Letter
C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Holmes, Edward/0000-0001-9596-3552
NR 11
TC 5
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD MAY
PY 2010
VL 10
IS 4
BP 431
EP 432
DI 10.1016/j.meegid.2010.03.006
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 609BN
UT WOS:000278629900001
PM 20304103
ER
PT J
AU Kash, JC
Qi, L
Dugan, VG
Jagger, BW
Hrabal, RJ
Memoli, MJ
Morens, DM
Taubenberger, JK
AF Kash, John C.
Qi, Li
Dugan, Vivien G.
Jagger, Brett W.
Hrabal, Rachel J.
Memoli, Matthew J.
Morens, David M.
Taubenberger, Jeffery K.
TI Prior infection with classical swine H1N1 influenza viruses is
associated with protective immunity to the 2009 pandemic H1N1 virus
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article
DE Antigenicity; H1N1; hemagglutinin; immunity; influenza; pandemic
ID HETEROSUBTYPIC IMMUNITY; LETHAL INFECTION; A VIRUSES; ORIGIN;
HEMAGGLUTININ; IMMUNIZATION; VACCINATION; RESPONSES; PROGRAM; HUMANS
AB Background
The 2009 H1N1 pandemic emerged even though seasonal H1N1 viruses have circulated for decades. Epidemio-logical evidence suggested that the current seasonal vaccine did not offer significant protection from the novel pandemic, and that people over the age of 50 might were less susceptible to infection.
Objectives
In a mouse challenge study with the 2009 pandemic H1N1 virus, we evaluated protective immune responses elicited by prior infection with human and swine influenza A viruses.
Results
Mice infected with A/Mexico/4108/2009 (Mex09) showed significant weight loss and 40% mortality. Prior infection with a 1976 classical swine H1N1 virus resulted in complete protection from Mex09 challenge. Prior infection with either a 2009 or a 1940 seasonal H1N1 influenza virus provided partial protection and a > 100-fold reduction in viral lung titers at day 4 post-infection.
Conclusions
These findings indicate that in experimental animals recently induced immunity to 1918-derived H1N1 seasonal influenza viruses, and to a 1976 swine influenza virus, afford a degree of protection against the 2009 pandemic virus. Implications of these findings are discussed in the context of accumulating data suggesting partial protection of older persons during the 2009 pandemic.
C1 [Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Morens, David M.] NIAID, Off Director, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 N Dr,MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
OI Hagey, Rachel/0000-0002-4368-3169
FU NIH; NIAID
FX We thank Dr. Brian Murphy (NIH/NIAID) for helpful discussions. We also
thank the Comparative Medicine Branch (NIH/NIAID) for assistance with
animal studies. This work was supported by the Intramural Research
Program of the NIH and the NIAID.
NR 33
TC 30
Z9 30
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD MAY
PY 2010
VL 4
IS 3
BP 121
EP 127
DI 10.1111/j.1750-2659.2010.00132.x
PG 7
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 579GF
UT WOS:000276356100003
PM 20409208
ER
PT J
AU Parameswaran, N
Thompson, RCA
Sundar, N
Pan, S
Johnson, M
Smith, NC
Grigg, ME
AF Parameswaran, N.
Thompson, R. C. A.
Sundar, N.
Pan, S.
Johnson, M.
Smith, N. C.
Grigg, M. E.
TI Non-archetypal Type II-like and atypical strains of Toxoplasma gondii
infecting marsupials of Australia
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Toxoplasma gondii; Non-archetypal; Genotype; Australia; Wildlife;
Marsupials
ID IDENTIFICATION; TRANSMISSION; GENOTYPE; DISEASE
AB Australia is geographically isolated and possesses a remarkable diversity of wildlife species. Marsupials are highly susceptible to infection with the cosmopolitan parasite Toxoplasma gondii. Of 46 marsupials screened for T. gondii by multilocus PCR-DNA sequencing at polymorphic genes (81, SAG3, GRA6, GRA7), 12 were PCR-positive; the majority (67%; 9/12) were infected by non-archetypal Type II-like or atypical strains. Six novel alleles were detected at 81, indicating greater diversity of genotypes than previously envisaged. Two isolates lethal to marsupials, were avirulent to mice. The data support the conclusion that Australia's isolation may have favoured the persistence of non-archetypal ancestral genotypes. Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.
C1 [Parameswaran, N.; Thompson, R. C. A.; Pan, S.] Murdoch Univ, WHO Collaborating Ctr Mol Epidemiol Parasit Infec, Sch Vet & Biomed Sci, Murdoch, WA 6150, Australia.
[Sundar, N.; Grigg, M. E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Johnson, M.; Smith, N. C.] Univ Technol Sydney, Inst Biotechnol Infect Dis, Sydney, NSW 2007, Australia.
RP Thompson, RCA (reprint author), Murdoch Univ, WHO Collaborating Ctr Mol Epidemiol Parasit Infec, Sch Vet & Biomed Sci, Murdoch, WA 6150, Australia.
EM A.thompson@murdoch.edu.au; griggm@niaid.nih.gov
FU Australian Research Council; Department of Environment and Conservation
in Western Australia; Intramural Research Program of the National
Institutes of Health (NIH); National Institute of Allergy and Infectious
Diseases (NIAID)
FX This work was supported by the Australian Research Council, Department
of Environment and Conservation in Western Australia, Intramural
Research Program of the National Institutes of Health (NIH) and National
Institute of Allergy and Infectious Diseases (NIAID). M.E.G. is a
scholar of the Canadian Institute for Advanced Research (CIFAR) Program
for Integrated Microbial Biodiversity. We also gratefully acknowledge
Simone Vitali and Paul Eden from Perth Zoo (Australia) and Adrian Wayne,
Peter Mawson and Glen Goudie for their immense help in collection of
specimens, and Alan Johnson for generously providing the archived
Tasmanian samples that were originally isolated by the late Barry
Munday. We also wish to thank Dr David Obendorf for kindly providing
case histories for these samples.
NR 20
TC 24
Z9 28
U1 2
U2 23
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
J9 INT J PARASITOL
JI Int. J. Parasit.
PD MAY
PY 2010
VL 40
IS 6
BP 635
EP 640
DI 10.1016/j.ijpara.2010.02.008
PG 6
WC Parasitology
SC Parasitology
GA 597CJ
UT WOS:000277733200001
PM 20346947
ER
PT J
AU Zheng, YL
Kosti, O
Loffredo, CA
Bowman, E
Mechanic, L
Perlmutter, D
Jones, R
Shields, PG
Harris, CC
AF Zheng, Yun-Ling
Kosti, Ourania
Loffredo, Christopher A.
Bowman, Elise
Mechanic, Leah
Perlmutter, Donna
Jones, Raymond
Shields, Peter G.
Harris, Curtis C.
TI Elevated lung cancer risk is associated with deficiencies in cell cycle
checkpoints: genotype and phenotype analyses from a case-control study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lung cancer; cell cycle checkpoints; G(2)/M checkpoint; DNA damage;
genotype-phenotype correlation
ID NUCLEOTIDE EXCISION-REPAIR; INDUCED DNA-ADDUCTS; WILD-TYPE P53;
AFRICAN-AMERICANS; ATAXIA-TELANGIECTASIA; ETHNIC-DIFFERENCES;
GENETIC-VARIATION; CHROMATID DAMAGE; BREAST-CANCER; X-IRRADIATION
AB Cell cycle checkpoints play critical roles in the maintenance of genomic integrity and inactivation of checkpoint genes are frequently perturbed in most cancers. In a case-control study of 299 non-small cell lung cancer cases and 550 controls in Baltimore, we investigated the association between gamma-radiation-induced G(2)/M arrest in cultured blood lymphocytes and lung cancer risk, and examined genotype-phenotype correlations between genetic polymorphisms of 20 genes involving in DNA repair and cell cycle control and 7-radiation-induced G(2)/M arrest. The study was specifically designed to examine race and gender differences in risk factors. Our data indicated that a less efficient DNA damage-induced G(2)/M checkpoint was associated with an increased risk of lung cancer in African American women with an adjusted odds ratio (OR) of 2.63 (95% Cl = 1.01-7.26); there were no statistically significant associations for Caucasians, or African American men. When the African American women were categorized into quartiles, a significant reverse trend of decreased G2/M checkpoint function and increased lung cancer risk was present, with lowest-vs.-highest quartile OR of 13.72 (95% CI = 2.30-81.92, P(trend) < 0.01). Genotype-phenotype correlation analysis indicated that polymorphisms in ATM, CDC25C, CDKNIA, BRCA2, ERCC6, TP53, and TP53BP1 genes were significantly associated with the 7-radiation-induced G(2)/M arrest phenotype. This study provides evidence that a less efficient G(2)/M checkpoint is significantly associated with lung cancer risk in African American women. The data also suggested that the function of G(2)/M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control.
C1 [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zheng, Yun-Ling; Kosti, Ourania; Loffredo, Christopher A.; Shields, Peter G.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Genet & Epidemiol Program, Washington, DC USA.
[Perlmutter, Donna; Jones, Raymond] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
RI Shields, Peter/I-1644-2012
FU Intramural NIH HHS [Z01 BC005480-23]
NR 53
TC 14
Z9 14
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2010
VL 126
IS 9
BP 2199
EP 2210
DI 10.1002/ijc.24771
PG 12
WC Oncology
SC Oncology
GA 576UD
UT WOS:000276173700019
PM 19626602
ER
PT J
AU Bhatia, K
Goedert, JJ
Modali, R
Preiss, L
Ayers, LW
AF Bhatia, Kishor
Goedert, James J.
Modali, Rama
Preiss, Liliana
Ayers, Leona W.
TI Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative
abundance and oncogene expression
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE Merkel cell carcinoma; MCPyV; oncogenesis; skin cancer
ID POTENTIAL DIAGNOSTIC PITFALL; ENDOTHELIAL-CELLS; HUMAN CANCER;
T-ANTIGEN; SARCOMA; SV40; INFECTION; GENE; SKIN; TDT
AB Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06-1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p < 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p < 0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.
C1 [Bhatia, Kishor; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Modali, Rama] Bioserve Biotechnol Ltd, Laurel, MD USA.
[Preiss, Liliana] RTI Int, Rockville, MD USA.
[Ayers, Leona W.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA.
RP Bhatia, K (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM bhatiak@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010150-08, Z01 CP010176-08]
NR 24
TC 82
Z9 82
U1 0
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2010
VL 126
IS 9
BP 2240
EP 2246
DI 10.1002/ijc.24676
PG 7
WC Oncology
SC Oncology
GA 576UD
UT WOS:000276173700023
PM 19551862
ER
PT J
AU Walker, AM
Stevens, JJ
Ndebele, K
Tchounwou, PB
AF Walker, Alice M.
Stevens, Jacqueline J.
Ndebele, Kenneth
Tchounwou, Paul B.
TI Arsenic Trioxide Modulates DNA Synthesis and Apoptosis in Lung Carcinoma
Cells
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE arsenic trioxide (As(2)O(3)); [(3)H]thymidine incorporation; apoptosis;
cell cycle regulation; p38 MAP kinase; caspase-3 fluorescein
isothiocyanate (FITC)
ID IN-VITRO; CANCER CELLS; CYCLE ARREST; ACTIVATION; MECHANISMS; BREAST;
GROWTH; EXPRESSION; INDUCTION; BCL-2
AB Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not entirely delineated. The primary objective of this research was to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic-induced apoptosis is mediated via caspase activation, p38 mitogen-activated protein kinase (MAPK), and cell cycle arrest. To achieve this goal, lung cancer cells (A549) were exposed to various concentrations (0, 2, 4, 6, 8, and 10 mu g/mL) of arsenic trioxide for 48 h. The effect of arsenic trioxide on DNA synthesis was determined by the [(3)H] thymidine incorporation assay. Apoptosis was determined by the caspase-3 fluorescein isothiocyanate (FITC) assay, p38 MAP kinase activity was determined by an immunoblot assay, and cell-cycle analysis was evaluated by the propidium iodide assay. The [(3)H] thymidine-incorporation assay revealed a dose-related cytotoxic response at high levels of exposure. Furthermore, arsenic trioxide modulated caspase 3 activity and induced p38 MAP kinase activation in A549 cells. However, cell-cycle studies showed no statistically significant differences in DNA content at subG1 check point between control and arsenic trioxide treated cells.
C1 [Walker, Alice M.; Stevens, Jacqueline J.; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
[Ndebele, Kenneth] Jackson State Univ, Lab Canc Immunol Target Identificat & Validat, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 JR Lynch St,Box 18540, Jackson, MS 39217 USA.
EM alice.m.walker@jsums.edu; jacqueline.j.stevens@jsums.edu;
kenneth.ndebele@jsums.edu; paul.b.tchounwou@jsums.edu
FU National Institutes of Health through NCRR-RCMI Center for Environmental
Health at Jackson State University [5G12RR013459-12]; US Department of
Education [P031B040101]
FX This research was supported in part by a grant from the National
Institutes of Health (Grant No. 5G12RR013459-12), through the NCRR-RCMI
Center for Environmental Health at Jackson State University, and in part
by a grant from the US Department of Education (Grant # P031B040101),
through the Title III Graduate Education Program.
NR 34
TC 23
Z9 26
U1 1
U2 6
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2010
VL 7
IS 5
BP 1996
EP 2007
DI 10.3390/ijerph7051996
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 601YW
UT WOS:000278105200010
PM 20632473
ER
PT J
AU Yedjou, CG
Milner, JN
Howard, CB
Tchounwou, PB
AF Yedjou, Clement G.
Milner, Jessica N.
Howard, Carolyn B.
Tchounwou, Paul B.
TI Basic Apoptotic Mechanisms of Lead Toxicity in Human Leukemia (Hl-60)
Cells
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE lead nitrate; HL-60 cells; annexin V; caspase-3; flow cytometry;
apoptosis
ID CARCINOMA HEPG(2) CELLS; TRANSCRIPTIONAL ACTIVATION; STRESS GENES; RAT;
EXPOSURE; EXPRESSION; NEURONS; DEATH
AB Lead exposure represents a medical and public health emergency, especially in children consuming high amounts of lead-contaminated flake paints. It may also cause hematological effects to people of all ages. Recent studies in our laboratory have indicated that apoptosis may be associated with the lead-induced oxidative stress and DNA damage. However, the mechanisms underlying its effect on lymphocytes are still largely unknown. Therefore, the aim of the present study was to investigate the apoptotic mechanisms of lead nitrate [Pb(NO(3))(2)] using HL-60 cells as a test model. HL-60 cells were treated with different concentrations of Pb(NO(3))(2) for 24 h prior to cell viability assay and flow cytometry assessment. The results obtained from the trypan blue exclusion test indicated that at very low concentration, Pb(NO(3))(2) has no effect on the viability of HL-60 cells. A significant (p < 0.05) decrease in cell viability was observed when exposed to high level of Pb(NO(3))(2). Data generated from the flow cytometric assessment indicated that Pb(NO(3))(2) exposure significantly (p < 0.05) increased the proportion of annexin V positive cells (apoptotic cells) compared to the control. Pb(NO(3))(2) induced apoptosis of HL-60 cells was associated with the activation of caspase-3. In summary, these studies demonstrated that Pb(NO(3))(2) represents an apoptosis-inducing agent in HL-60 promyelocytic leukemia cells and its apoptotic mechanism functions, at least in part via, induction of phosphatidylserine externalization and caspase-3 activation.
C1 [Yedjou, Clement G.; Milner, Jessica N.; Howard, Carolyn B.; Tchounwou, Paul B.] Jackson State Univ, Cellom & Toxicogen Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Yedjou, CG (reprint author), Jackson State Univ, Cellom & Toxicogen Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA.
EM clement.yedjou@jsums.edu; jessica.n.milner@jsums.edu;
carolyn.b.howard@jsums.edu; paul.b.tchounwou@jsums.edu
FU Mississippi Functional Genomics Network (MFGN) at the University of
Southern Mississippi; National Institute of Health through RCMI-Center
for Environmental Health at Jackson State University
FX This research was financially supported in part by a grant from the
Mississippi Functional Genomics Network (MFGN) at the University of
Southern Mississippi, and in part by a grant from the National Institute
of Health (Grant No. 2G12RR013459-11), through the RCMI-Center for
Environmental Health at Jackson State University.
NR 21
TC 16
Z9 18
U1 1
U2 9
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2010
VL 7
IS 5
BP 2008
EP 2017
DI 10.3390/ijerph7052008
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 601YW
UT WOS:000278105200011
PM 20623007
ER
PT J
AU Stevens, JJ
Graham, B
Walker, AM
Tchounwou, PB
Rogers, C
AF Stevens, Jacqueline J.
Graham, Barbara
Walker, Alice M.
Tchounwou, Paul B.
Rogers, Christian
TI The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in
Human Colon Cancer Cells
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE Arsenic trioxide; HT-29 cells; [(3)H]thymidine incorporation assay;
genotoxicity; comet assay
ID ACUTE PROMYELOCYTIC LEUKEMIA; MOLECULAR-MECHANISMS; IN-VITRO; OXIDATIVE
STRESS; SODIUM ARSENITE; DRINKING-WATER; COMET ASSAY; CARCINOGENESIS;
APOPTOSIS; DAMAGE
AB Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 mu g/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [(3)H] thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 mu g/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 mu g/mL). The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [(3)H] thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells.
C1 [Stevens, Jacqueline J.; Graham, Barbara; Walker, Alice M.; Tchounwou, Paul B.; Rogers, Christian] Jackson State Univ, Mol & Cellular Biol Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Stevens, JJ (reprint author), Jackson State Univ, Mol & Cellular Biol Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 JR Lynch St,Box 18540, Jackson, MS 39217 USA.
EM Jacqueline.j.stevens@jsums.edu; barbara.e.graham@jsums.edu;
alice.m.walker@jsums.edu; paul.b.tchounwou@jsums.edu;
christian.s.rogers@jsums.edu
FU National Institutes of Health through the NCRR-RCMI Center for
Environmental Health [2G12RR013459]; Jackson State University
[GM007672-29]
FX This research supported in part by a grant from the National Institutes
of Health (Grant NO. 2G12RR013459) through the NCRR-RCMI Center for
Environmental Health and in part by a grant from Minority Access to
Research Careers/Undergraduate Student Training in Academic Research
(MARC/U*STAR) Program (Grant NO. GM007672-29) at Jackson State
University.
NR 52
TC 14
Z9 16
U1 2
U2 12
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2010
VL 7
IS 5
BP 2018
EP 2032
DI 10.3390/ijerph7052018
PG 15
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 601YW
UT WOS:000278105200012
PM 20623008
ER
PT J
AU Ndebele, K
Graham, B
Tchounwou, PB
AF Ndebele, Kenneth
Graham, Barbara
Tchounwou, Paul B.
TI Estrogenic Activity of Coumestrol, DDT, and TCDD in Human Cervical
Cancer Cells
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE xenoestrogens; Coumestrol; DDT; TCDD; Cell Cycle
ID DOSE-RESPONSE ASSESSMENT; T-CELL; ENVIRONMENTAL ESTROGENS;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; GENE-EXPRESSION; SEX STEROIDS;
BISPHENOL-A; ENDOCRINE DISRUPTERS; CYTOKINE PRODUCTION; ARYL-HYDROCARBON
AB Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells) as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD)-a herbicide and DDT-a pesticide) on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-beta-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer.
C1 [Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
[Ndebele, Kenneth; Graham, Barbara] Jackson State Univ, Lab Canc Immunol Target Identificat & Validat, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA.
EM kenneth.ndebele@jsums.edu; Barbara.e.graham@jsums.edu;
paul.b.tchounwou@jsums.edu
FU NIH-RCMI [G12RR013459]
FX This research was financially supported in part by NIH-RCMI grant #
G12RR013459.
NR 57
TC 16
Z9 17
U1 1
U2 7
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2010
VL 7
IS 5
BP 2045
EP 2056
DI 10.3390/ijerph7052045
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 601YW
UT WOS:000278105200014
PM 20623010
ER
PT J
AU Brown, JA
AF Brown, Jay A.
TI Using a Relational Database to Index Infectious Disease Information
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article; Proceedings Paper
CT 6th International Symposium on Recent Advances in Environmental Health
Research
CY SEP 13-16, 2009
CL Jackson, MS
SP Jackson State Univ
DE decision support; relational database; infectious diseases; public
health informatics; early detection; differential diagnosis; indexing
information; knowledge mapping
ID PUBLIC-HEALTH MANAGEMENT; BIOLOGICAL WEAPON; COMPUTER-PROGRAM;
BIOTERRORISM; DIAGNOSIS; FEVER; PATIENT; ANTHRAX; GIDEON
AB Mapping medical knowledge into a relational database became possible with the availability of personal computers and user-friendly database software in the early 1990s. To create a database of medical knowledge, the domain expert works like a mapmaker to first outline the domain and then add the details, starting with the most prominent features. The resulting "intelligent database" can support the decisions of healthcare professionals. The intelligent database described in this article contains profiles of 275 infectious diseases. Users can query the database for all diseases matching one or more specific criteria (symptom, endemic region of the world, or epidemiological factor). Epidemiological factors include sources (patients, water, soil, or animals), routes of entry, and insect vectors. Medical and public health professionals could use such a database as a decision-support software tool.
C1 Natl Lib Med, Specialized Informat Serv, Bethesda, MD 20892 USA.
RP Brown, JA (reprint author), Natl Lib Med, Specialized Informat Serv, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA.
EM brownjay@haz-map.com
NR 52
TC 1
Z9 1
U1 0
U2 5
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2010
VL 7
IS 5
BP 2177
EP 2190
DI 10.3390/ijerph7052177
PG 14
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 601YW
UT WOS:000278105200022
PM 20623018
ER
PT J
AU Haymond, M
Anderson, B
Bush, C
Gunn, S
Holden, H
Jones, M
Hwu, K
McGirk, S
Mckay, S
Thamotharan, S
Schreiner, B
Zarate, M
Cuttler, L
Abrams, E
Casey, T
Dahms, W
Drotar, D
Huestis, S
Ievers-Landis, C
McGuigan, P
Sundararajan, S
Geffner, M
Chang, N
Dreimane, D
Halvorson, M
Hernandez, S
Kaufman, F
Mansilla, V
Ortiz, R
Ward, A
Wexler, K
Yasuda, P
Katz, LL
Berkowitz, R
Boyd, S
Carchidi, C
Johnson, B
Kaplan, J
Keating, C
Kneeshaw-Price, S
Lassiter, C
Lipman, T
Magge, S
McGinley, G
Schwartzman, B
Willi, S
Arslanian, S
Bacha, F
Foster, S
Galvin, B
Hannon, T
Kriska, A
Libman, I
Marcus, M
Porter, K
Songer, T
Venditti, E
Goland, R
Cain, R
Fennoy, I
Gallagher, D
Kringas, P
Leibel, N
Motaghedi, R
Ng, D
Ovalles, M
Pellizzari, M
Rapaport, R
Robbins, K
Seidman, D
Siegel-Czarkowski, L
Speiser, P
Laffel, L
Goebel-Fabbri, A
Hall, M
Higgins, L
Malloy, M
Milaszewski, K
Orkin, L
Rodriguez-Ventura, A
Nathan, D
Bissett, L
Blumenthal, K
Delahanty, L
Goldman, V
Goseco, A
Larkin, M
Levitsky, L
McEachern, R
Milaszewski, K
Norman, D
Nwosu, B
Park-Bennett, S
Richards, D
Sherry, N
Steiner, B
Tollefsen, S
Carnes, S
Dempsher, D
Flomo, D
Floreen, A
Kociela, V
Whelan, T
Wolff, B
Weinstock, R
Bowerman, D
Bulger, J
Duncan, K
Franklin, R
Hartsig, J
Izquierdo, R
Kanaley, J
Kearns, J
Meyer, S
Saletsky, R
Trief, P
Zeitler, P
Abramson, N
Bradhurst, A
Celona-Jacobs, N
Glazner, J
Higgins, J
Hoe, F
Klingensmith, G
Nadeau, K
Strike, H
Witten, T
Copeland, K
Brown, R
Chadwick, J
Chalmers, L
Macha, C
Nordyke, A
Poulsen, T
Pratt, L
Preske, J
Schanuel, J
Smith, J
Sternlof, S
Swisher, R
Hale, D
Amodei, N
Barajas, R
Cody, C
Haffner, S
Hernandez, J
Ibarra, C
Lynch, J
Morales, E
Rivera, S
Rupert, G
Wauters, A
White, N
Arbelaez, A
Jones, J
Jones, T
Sadler, M
Tanner, M
Timpson, A
Welch, R
Caprio, S
Grey, M
Guandalini, C
Lavietes, S
Mignosa, M
Rose, P
Syme, A
Tamborlane, W
Hirst, K
Coombs, L
Edelstein, S
Grover, N
Long, C
Pyle, L
Linder, B
Marcovina, S
Chmielewski, J
Ramirez, M
Strylewicz, G
Shepherd, J
Fan, B
Marquez, L
Sherman, M
Wang, J
Mayer-Davis, E
Liu, Y
Nichols, M
Wilfley, D
Aldrich-Rasche, D
Franklin, K
Leibach, G
Massmann, C
Mills, M
O'Brien, D
Patterson, J
Tibbs, T
Van Buren, D
Zhang, P
Palmert, M
Epstein, L
Silverstein, J
AF Haymond, M.
Anderson, B.
Bush, C.
Gunn, S.
Holden, H.
Jones, M.
Hwu, K.
McGirk, S.
McKay, S.
Thamotharan, S.
Schreiner, B.
Zarate, M.
Cuttler, L.
Abrams, E.
Casey, T.
Dahms, W.
Drotar, D.
Huestis, S.
Ievers-Landis, C.
McGuigan, P.
Sundararajan, S.
Geffner, M.
Chang, N.
Dreimane, D.
Halvorson, M.
Hernandez, S.
Kaufman, F.
Mansilla, V.
Ortiz, R.
Ward, A.
Wexler, K.
Yasuda, P.
Katz, L. Levitt
Berkowitz, R.
Boyd, S.
Carchidi, C.
Johnson, B.
Kaplan, J.
Keating, C.
Kneeshaw-Price, S.
Lassiter, C.
Lipman, T.
Magge, S.
McGinley, G.
Schwartzman, B.
Willi, S.
Arslanian, S.
Bacha, F.
Foster, S.
Galvin, B.
Hannon, T.
Kriska, A.
Libman, I.
Marcus, M.
Porter, K.
Songer, T.
Venditti, E.
Goland, R.
Cain, R.
Fennoy, I.
Gallagher, D.
Kringas, P.
Leibel, N.
Motaghedi, R.
Ng, D.
Ovalles, M.
Pellizzari, M.
Rapaport, R.
Robbins, K.
Seidman, D.
Siegel-Czarkowski, L.
Speiser, P.
Laffel, L.
Goebel-Fabbri, A.
Hall, M.
Higgins, L.
Malloy, M.
Milaszewski, K.
Orkin, L.
Rodriguez-Ventura, A.
Nathan, D.
Bissett, L.
Blumenthal, K.
Delahanty, L.
Goldman, V.
Goseco, A.
Larkin, M.
Levitsky, L.
McEachern, R.
Milaszewski, K.
Norman, D.
Nwosu, B.
Park-Bennett, S.
Richards, D.
Sherry, N.
Steiner, B.
Tollefsen, S.
Carnes, S.
Dempsher, D.
Flomo, D.
Floreen, A.
Kociela, V.
Whelan, T.
Wolff, B.
Weinstock, R.
Bowerman, D.
Bulger, J.
Duncan, K.
Franklin, R.
Hartsig, J.
Izquierdo, R.
Kanaley, J.
Kearns, J.
Meyer, S.
Saletsky, R.
Trief, P.
Zeitler, P.
Abramson, N.
Bradhurst, A.
Celona-Jacobs, N.
Glazner, J.
Higgins, J.
Hoe, F.
Klingensmith, G.
Nadeau, K.
Strike, H.
Witten, T.
Copeland, K.
Brown, R.
Chadwick, J.
Chalmers, L.
Macha, C.
Nordyke, A.
Poulsen, T.
Pratt, L.
Preske, J.
Schanuel, J.
Smith, J.
Sternlof, S.
Swisher, R.
Hale, D.
Amodei, N.
Barajas, R.
Cody, C.
Haffner, S.
Hernandez, J.
Ibarra, C.
Lynch, J.
Morales, E.
Rivera, S.
Rupert, G.
Wauters, A.
White, N.
Arbelaez, A.
Jones, J.
Jones, T.
Sadler, M.
Tanner, M.
Timpson, A.
Welch, R.
Caprio, S.
Grey, M.
Guandalini, C.
Lavietes, S.
Mignosa, M.
Rose, P.
Syme, A.
Tamborlane, W.
Hirst, K.
Coombs, L.
Edelstein, S.
Grover, N.
Long, C.
Pyle, L.
Linder, B.
Marcovina, S.
Chmielewski, J.
Ramirez, M.
Strylewicz, G.
Shepherd, J.
Fan, B.
Marquez, L.
Sherman, M.
Wang, J.
Mayer-Davis, E.
Liu, Y.
Nichols, M.
Wilfley, D.
Aldrich-Rasche, D.
Franklin, K.
Leibach, G.
Massmann, C.
Mills, M.
O'Brien, D.
Patterson, J.
Tibbs, T.
Van Buren, D.
Zhang, P.
Palmert, M.
Epstein, L.
Silverstein, J.
CA TODAY Study Grp
TI Design of a family-based lifestyle intervention for youth with type 2
diabetes: the TODAY study (vol 34, pg 946, 2010)
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Correction
C1 [Haymond, M.; Anderson, B.; Bush, C.; Gunn, S.; Holden, H.; Jones, M.; Hwu, K.; McGirk, S.; McKay, S.; Thamotharan, S.; Schreiner, B.; Zarate, M.] Baylor Coll Med, Houston, TX 77030 USA.
[Cuttler, L.; Abrams, E.; Casey, T.; Dahms, W.; Drotar, D.; Huestis, S.; Ievers-Landis, C.; McGuigan, P.; Sundararajan, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Geffner, M.; Chang, N.; Dreimane, D.; Halvorson, M.; Hernandez, S.; Kaufman, F.; Mansilla, V.; Ortiz, R.; Ward, A.; Wexler, K.; Yasuda, P.] Childrens Hosp Los Angeles, Los Angeles, CA USA.
[Katz, L. Levitt; Berkowitz, R.; Boyd, S.; Carchidi, C.; Johnson, B.; Kaplan, J.; Keating, C.; Kneeshaw-Price, S.; Lassiter, C.; Lipman, T.; Magge, S.; McGinley, G.; Schwartzman, B.; Willi, S.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Arslanian, S.; Bacha, F.; Foster, S.; Galvin, B.; Hannon, T.; Kriska, A.; Libman, I.; Marcus, M.; Porter, K.; Songer, T.; Venditti, E.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Goland, R.; Cain, R.; Fennoy, I.; Gallagher, D.; Kringas, P.; Leibel, N.; Motaghedi, R.; Ng, D.; Ovalles, M.; Pellizzari, M.; Rapaport, R.; Robbins, K.; Seidman, D.; Siegel-Czarkowski, L.; Speiser, P.] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Milaszewski, K.; Nathan, D.; Bissett, L.; Blumenthal, K.; Delahanty, L.; Goldman, V.; Goseco, A.; Larkin, M.; Levitsky, L.; McEachern, R.; Norman, D.; Nwosu, B.; Park-Bennett, S.; Richards, D.; Sherry, N.; Steiner, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tollefsen, S.; Carnes, S.; Dempsher, D.; Flomo, D.; Floreen, A.; Kociela, V.; Whelan, T.; Wolff, B.] St Louis Univ, St Louis, MO 63103 USA.
[Weinstock, R.; Bowerman, D.; Bulger, J.; Duncan, K.; Franklin, R.; Hartsig, J.; Izquierdo, R.; Kanaley, J.; Kearns, J.; Meyer, S.; Saletsky, R.; Trief, P.] SUNY Upstate Med Univ, Syracuse, NY USA.
[Zeitler, P.; Celona-Jacobs, N.; Glazner, J.; Higgins, J.; Hoe, F.; Klingensmith, G.; Nadeau, K.; Strike, H.; Witten, T.] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
[Copeland, K.; Brown, R.; Chadwick, J.; Chalmers, L.; Macha, C.; Nordyke, A.; Poulsen, T.; Pratt, L.; Preske, J.; Schanuel, J.; Smith, J.; Sternlof, S.; Swisher, R.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA.
[Hale, D.; Amodei, N.; Barajas, R.; Cody, C.; Haffner, S.; Hernandez, J.; Ibarra, C.; Lynch, J.; Morales, E.; Rivera, S.; Rupert, G.; Wauters, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[White, N.; Arbelaez, A.; Jones, J.; Jones, T.; Sadler, M.; Tanner, M.; Timpson, A.; Welch, R.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Caprio, S.; Grey, M.; Guandalini, C.; Lavietes, S.; Mignosa, M.; Rose, P.; Syme, A.; Tamborlane, W.] Yale Univ, New Haven, CT 06520 USA.
[Hirst, K.; Coombs, L.; Edelstein, S.; Grover, N.; Long, C.; Pyle, L.] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA.
[Linder, B.] NIDDK, Bethesda, MD 20892 USA.
[Marcovina, S.; Chmielewski, J.; Ramirez, M.; Strylewicz, G.] Washington Univ, NW Lipid Res Labs, Cent Blood Lab, St Louis, MO 63130 USA.
[Shepherd, J.; Fan, B.; Marquez, L.; Sherman, M.; Wang, J.] Univ Calif San Francisco, DEXA Reading Ctr, San Francisco, CA 94143 USA.
[Mayer-Davis, E.; Liu, Y.; Nichols, M.] Univ S Carolina, Diet Assessment Ctr, Columbia, SC 29208 USA.
[Wilfley, D.; Aldrich-Rasche, D.; Franklin, K.; Leibach, G.; Massmann, C.; Mills, M.; O'Brien, D.; Patterson, J.; Tibbs, T.; Van Buren, D.] Washington Univ, Lifestyle Program Core, St Louis, MO 63130 USA.
[Palmert, M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Epstein, L.] SUNY Buffalo, Buffalo, NY 14260 USA.
[Silverstein, J.] Univ Florida, Gainesville, FL 32611 USA.
[Zhang, P.] CDC, Atlanta, GA 30333 USA.
RP Haymond, M (reprint author), Baylor Coll Med, Houston, TX 77030 USA.
NR 1
TC 1
Z9 1
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD MAY
PY 2010
VL 34
IS 5
BP 946
EP 946
DI 10.1038/ijo.2009.247
PG 1
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 593EP
UT WOS:000277435700020
ER
PT J
AU FitzGerald, TJ
Bisop-Jodoin, M
Cicchetti, MG
Hanusik, R
Kessel, S
Laurie, F
McCarten, KM
Moni, J
Pieters, RS
Rosen, N
Ulin, K
Urie, M
Chauvenet, AR
Constine, LS
Deye, J
Vikram, B
Friedman, D
Marcus, RB
Mendenhall, NP
Williams, JL
Purdy, J
Saltz, J
Schwartz, CL
White, KS
Wolden, S
AF FitzGerald, Thomas J.
Bisop-Jodoin, Maryann
Cicchetti, M. Giulia
Hanusik, Richard
Kessel, Sandy
Laurie, Fran
McCarten, Kathleen M.
Moni, Janaki
Pieters, Richard S.
Rosen, Nancy
Ulin, Kenneth
Urie, Marcia
Chauvenet, Allen R.
Constine, Louis S.
Deye, James
Vikram, Bhadrasain
Friedman, Debra
Marcus, Robert B., Jr.
Mendenhall, Nancy P.
Williams, Jon L.
Purdy, James
Saltz, Joel
Schwartz, Cindy L.
White, Keith S.
Wolden, Suzanne
TI QUALITY OF RADIOTHERAPY REPORTING IN RANDOMIZED CONTROLLED TRIALS OF
HODGKIN'S LYMPHOMA AND NON-HODGKIN'S LYMPHOMA: IN REGARD TO BEKELMAN AND
YAHALOM (INT J RADIAT ONCOL BIOL PHYS 2009;73:492-498)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Letter
ID DISEASE
C1 [Chauvenet, Allen R.] W Virginia Univ, Hlth Sci Ctr Charleston, Charleston, WV 25304 USA.
[Constine, Louis S.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Deye, James; Vikram, Bhadrasain] NCI, Bethesda, MD 20892 USA.
[Friedman, Debra] Vanderbilt Univ, Vanderbilt Childrens Hosp, Nashville, TN USA.
[Marcus, Robert B., Jr.; Mendenhall, Nancy P.; Williams, Jon L.] Univ Florida, Gainesville, FL 32611 USA.
[Purdy, James] UC Davis Canc Ctr, Davis, CA USA.
[Saltz, Joel] Emory Univ, Atlanta, GA 30322 USA.
[Schwartz, Cindy L.] Rhode Isl Hosp, Providence, RI 02903 USA.
[Wolden, Suzanne] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
FU NCI NIH HHS [U10 CA029511-24, U10 CA029511, U10 CA029511-20, U10
CA029511-21, U10 CA029511-22, U10 CA029511-23, U10 CA029511-25, U10
CA029511-26, U10 CA029511-27, U10 CA029511-28, U10 CA029511-29, U10
CA029511-30]
NR 9
TC 5
Z9 5
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAY 1
PY 2010
VL 77
IS 1
BP 315
EP 316
DI 10.1016/j.ijrobp.2009.12.051
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 588XC
UT WOS:000277106900047
PM 20394859
ER
PT J
AU Wolmark, N
Curran, WJ
Vicini, F
White, J
Costantino, JP
Arthur, D
Kuske, R
Rabinovitch, R
Julian, TB
Parda, DS
AF Wolmark, Norman
Curran, Walter J.
Vicini, Frank
White, Julia
Costantino, Joseph P.
Arthur, Douglas
Kuske, Robert
Rabinovitch, Rachel
Julian, Thomas B.
Parda, David S.
TI RESPONSE TO "UNACCEPTABLE COSMESIS IN A PROTOCOL INVESTIGATING
INTENSITY-MODULATED RADIOTHERAPY WITH ACTIVE BREATHING CONTROL FOR
ACCELERATED PARTIAL-BREAST IRRADIATION" (INT J RADIAT ONCOL BIOL PHYS
2010;76:71-78) AND "TOXICITY OF THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY
FOR ACCELERATED PARTIAL BREAST IRRADIATION" INT J RADIAT ONCOL BIOL PHYS
2009;75:1290-1296)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Letter
C1 [Wolmark, Norman; Julian, Thomas B.] Allegheny Gen Hosp, Dept Human Oncol, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
[Curran, Walter J.] Winship Canc Inst, Radiat Dept, Atlanta, GA USA.
[Curran, Walter J.] Amer Coll Radiol, Radiat Therapy Oncol Grp, Philadelphia, PA USA.
[Vicini, Frank] William Beaumont Hosp, Natl Surg Adjuvant Breast & Bowel Project, Dept Oncol, Royal Oak, MI 48072 USA.
[White, Julia] Med Coll Wisconsin, Dept Radiat Oncol, Amer Coll Radiol, Radiat Therapy Oncol Grp, Milwaukee, WI 53226 USA.
[Costantino, Joseph P.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15261 USA.
[Arthur, Douglas] Virginia Commonwealth Univ, Dept Radiat Oncol, Med Ctr, Natl Surg Adjuvant Breast & Bowel Project, Richmond, VA USA.
[Kuske, Robert] Arizona Breast Canc Specialists, Natl Surg Adjuvant Breast & Bowel Project, Scottsdale, AZ USA.
[Rabinovitch, Rachel] Univ Colorado, Ctr Comprehens Canc, Dept Radiat Oncol, Radiat Therapy Oncol Grp,Amer Coll Radiol, Aurora, CO USA.
[Parda, David S.] Allegheny Gen Hosp, Dept Radiat Oncol, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
RP Wolmark, N (reprint author), Allegheny Gen Hosp, Dept Human Oncol, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
NR 2
TC 18
Z9 18
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAY 1
PY 2010
VL 77
IS 1
BP 317
EP 317
DI 10.1016/j.ijrobp.2009.12.033
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 588XC
UT WOS:000277106900052
PM 20394863
ER
PT J
AU Tokar, EJ
Diwan, BA
Waalkes, MP
AF Tokar, Erik J.
Diwan, Bhalchandra A.
Waalkes, Michael P.
TI Arsenic Exposure In Utero and Nonepidermal Proliferative Response in
Adulthood in Tg.AC Mice
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Article
DE arsenic; carcinogenesis; transplacental; rodent; adrenal tumors
ID MALE F344 RATS; DIMETHYLARSINIC ACID; URINARY-BLADDER; POSTNATAL
DIETHYLSTILBESTROL; GESTATIONAL EXPOSURE; DRINKING-WATER; CANCER;
CARCINOGENESIS; INDUCTION; TUMORS
AB To expand our knowledge on the transplacental carcinogenic potential of inorganic arsenic, pregnant Tg.AC mice received drinking water with 0, 42.5, or 85 ppm arsenite from gestation day 8 to 18. After birth, groups (n = 25) of offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) (2 mu g twice a week) for 36 weeks and were killed; nonskin tumors were assessed. Arsenic increased adrenal cortical adenomas (ACAs; 25%-29%) compared with control (0%) independent of TPA in all male groups. Arsenic increased urinary bladder (UB) hyperplasia in males, but only with TPA. Arsenic induced ACAs in all female groups (control 0%; arsenic 17%-26%). Arsenic-treated females had UB hyperplasia in most groups (control 0%; arsenic 26%-32%), with 2 UB papillomas. All arsenic-treated females had uterine hyperplasia (26%-40%; control 4%) independent of TPA, and 3 had uterine tumors. Thus, arsenic in utero rapidly induces ACAs and uterine and UB preneoplasias in Tg.AC mice, showing transplacental carcinogenic potential in yet another strain of mice.
C1 [Tokar, Erik J.; Waalkes, Michael P.] NIEHS, NCI, Res Triangle Pk, NC 27709 USA.
[Diwan, Bhalchandra A.] NCI, SAIC Frederick Inc, Frederick, MD USA.
RP Waalkes, MP (reprint author), NIEHS, NCI, 1,USA11 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NCI
[HHSN261200800001E]
FX The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: This research was
supported, in part, by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. This research was
funded, in part, with Federal funds from the NCI under contract
HHSN261200800001E.
NR 19
TC 15
Z9 15
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD MAY
PY 2010
VL 29
IS 3
BP 291
EP 296
DI 10.1177/1091581810362804
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 602FV
UT WOS:000278124800006
PM 20448261
ER
PT J
AU Ehler, M
Koch, K
AF Ehler, Martin
Koch, Karsten
TI THE CONSTRUCTION OF MULTIWAVELET BI-FRAMES AND APPLICATIONS TO
VARIATIONAL IMAGE DENOISING
SO INTERNATIONAL JOURNAL OF WAVELETS MULTIRESOLUTION AND INFORMATION
PROCESSING
LA English
DT Article
DE Wavelet bi-frames; variational approach; parameter choice; denoising
ID WAVELET SHRINKAGE; VANISHING MOMENTS; NOISE REMOVAL; BESOV-SPACES;
DOMAINS; TIGHT
AB We remove noise from images by solving a parameter depending variational problem. The choice of the parameter is essential for the success of the approach, and in order to compute a solution, the problem must be discretized. It is commonly known that the parameter choice according to the H-curve criterion performs well in combination with discretizations derived from a dyadic orthonormal wavelet basis. However, the concept of orthonormal wavelet bases is restrictive and bears limitations. In order to have a more flexible tool, we construct new nondyadic wavelet bi-frames by convolving scalar wavelets with wavelet vectors. We discretize the variational problem by these new bi-frames, and we verify that the H-curve method performs well for this much more flexible discretization technique.
C1 [Ehler, Martin] Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA.
[Ehler, Martin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Biophys, NIH, Bethesda, MD 20892 USA.
[Koch, Karsten] Univ Marburg, Dept Math & Comp Sci, D-35037 Marburg, Germany.
RP Ehler, M (reprint author), Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA.
EM ehlermar@math.umd.edu; koch@mathematik.uni-marburg.de
NR 37
TC 15
Z9 15
U1 0
U2 2
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 0219-6913
EI 1793-690X
J9 INT J WAVELETS MULTI
JI Int. J. Wavelets Multiresolut. Inf. Process.
PD MAY
PY 2010
VL 8
IS 3
BP 431
EP 455
DI 10.1142/S0219691310003560
PG 25
WC Computer Science, Software Engineering; Mathematics, Interdisciplinary
Applications
SC Computer Science; Mathematics
GA 603FM
UT WOS:000278194100006
ER
PT J
AU Forooghian, F
Kertes, PJ
Eng, KT
Agron, E
Chew, EY
AF Forooghian, Farzin
Kertes, Peter J.
Eng, Kenneth T.
Agron, Elvira
Chew, Emily Y.
TI Alterations in the Intraocular Cytokine Milieu after Intravitreal
Bevacizumab
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PROLIFERATIVE DIABETIC-RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR;
RETINAL-PIGMENT EPITHELIUM; AQUEOUS-HUMOR LEVELS; VITREOUS LEVELS;
MACULAR EDEMA; VITREORETINAL DISEASES; PREOPERATIVE ADJUNCT; TUMOR
ANGIOGENESIS; VEIN OCCLUSION
AB PURPOSE. Several complications after intravitreal bevacizumab (IVB) treatment have been described including tears of the retinal pigment epithelium and tractional retinal detachment. The etiology of these complications remains unclear. The purpose of this study was to characterize changes in the intraocular levels of inflammatory cytokines after IVB as a possible explanation for these complications.
METHODS. Twenty-nine patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) with IVB pretreatment were prospectively enrolled. Aqueous humor samples were taken at the time of IVB pretreatment and approximately 1 week later at the time of PPV. Multiplex cytokine arrays were used to assay 20 different cytokines. Multivariate general linear regression was performed to determine differences in cytokine levels between the two study visits. Proportional hazards regression was performed to determine the relationship between cytokine levels at PPV and postoperative outcomes.
RESULTS. After treatment with IVB, vascular endothelial growth factor (VEGF) concentrations in the aqueous humor decreased (P = 0.0003), whereas the concentrations of IL-8 and transforming growth factor (TGF)-beta(2) increased after IVB (P < 0.03). The level of IL-8 at the time of PPV was associated with the occurrence of recurrent VH after surgery (hazard ratio, 1.32; P = 0.02).
CONCLUSIONS. Alterations in the intraocular inflammatory cytokine milieu occur after IVB injection, possibly as a compensatory mechanism in response to VEGF inhibition. The increased concentrations of inflammatory cytokines after IVB may be clinically significant and may be responsible for some of the complications after IVB. (Invest Ophthalmol Vis Sci. 2010;51:2388-2392) DOI: 10.1167/iovs.09-4065
C1 [Forooghian, Farzin; Agron, Elvira; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Kertes, Peter J.; Eng, Kenneth T.] Univ Toronto, Dept Ophthalmol, Toronto, ON M5S 1A1, Canada.
RP Chew, EY (reprint author), NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU National Eye Institute/National Institutes of Health, Department of
Health; Human Services, Bethesda, MD
FX Supported by the intramural program funds and contracts from the
National Eye Institute/National Institutes of Health, Department of
Health and Human Services, Bethesda, MD.
NR 51
TC 33
Z9 35
U1 0
U2 2
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 MAY
PY 2010
VL 51
IS 5
BP 2388
EP 2392
DI 10.1167/iovs.09-4065
PG 5
WC Ophthalmology
SC Ophthalmology
GA 589UU
UT WOS:000277180500015
PM 20007836
ER
PT J
AU Permanyer, J
Navarro, R
Friedman, J
Pomares, E
Castro-Navarro, J
Marfany, G
Swaroop, A
Gonzalez-Duarte, R
AF Permanyer, Jon
Navarro, Rafael
Friedman, James
Pomares, Esther
Castro-Navarro, Joaquin
Marfany, Gemma
Swaroop, Anand
Gonzalez-Duarte, Roser
TI Autosomal Recessive Retinitis Pigmentosa with Early Macular Affectation
Caused by Premature Truncation in PROM1
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; FRAMESHIFT MUTATION; STARGARDT-DISEASE;
GENE; DEGENERATION; PROTEIN; PROMININ; IDENTIFICATION; CHOLESTEROL;
ORTHOLOG
AB PURPOSE. To identify the genetic basis of a large consanguineous Spanish pedigree affected with autosomal recessive retinitis pigmentosa (arRP) with premature macular atrophy and myopia.
METHODS. After a high-throughput cosegregation gene chip was used to exclude all known RP and Leber congenital amaurosis (LCA) candidates, genome-wide screening and linkage analysis were performed. Direct mutational screening identified the pathogenic mutation, and primers were designed to obtain the RT-PCR products for isoform characterization.
RESULTS. Mutational analysis detected a novel homozygous PROM1 mutation, c.869delG in exon 8 cosegregating with the disease. This variant causes a frameshift that introduces a premature stop codon, producing truncation of approximately two-thirds of the protein. Analysis of PROM1 expression in the lymphocytes of patients, carriers, and control subjects revealed an aberrant transcript that is degraded by the nonsense-mediated decay pathway, suggesting that the disease is caused by the absence of the PROM1 protein. Three (s2, s11 and s12) of the seven alternatively spliced isoforms reported in humans, accounted for 98% of the transcripts in the retina. Given that these three contained exon 8, no PROM1 isoform is expected in the affected retinas.
CONCLUSIONS. A remarkable clinical finding in the affected family is early macular atrophy with concentric spared areas. The authors propose that the hallmark of PROM1 truncating mutations is early and severe progressive degeneration of both rods and cones and highlight this gene as a candidate of choice to prioritize in the molecular genetic study of patients with non-canonical clinical peripheral and macular affectation. (Invest Ophthalmol Vis Sci. 2010;51:2656-2663) DOI:10.1167/iovs.09-4857
C1 [Permanyer, Jon; Pomares, Esther; Marfany, Gemma; Gonzalez-Duarte, Roser] Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Spain.
[Marfany, Gemma; Gonzalez-Duarte, Roser] Univ Barcelona, IBUB Inst Biomed, E-08028 Barcelona, Spain.
[Permanyer, Jon; Pomares, Esther; Marfany, Gemma; Gonzalez-Duarte, Roser] Inst Salud Carlos III, CIBERER, Barcelona, Spain.
[Navarro, Rafael] Inst Microcirugia Ocular, Barcelona, Spain.
[Friedman, James; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Castro-Navarro, Joaquin] Hosp Univ Cent Asturias, Unidad Retina, Serv Oftalmol, Oviedo, Spain.
RP Gonzalez-Duarte, R (reprint author), Univ Barcelona, Fac Biol, Dept Genet, Avda Diagonal 645, E-08028 Barcelona, Spain.
EM rgonzalez@ub.edu
RI Marfany, Gemma/I-5668-2015;
OI Marfany, Gemma/0000-0001-7941-983X; Swaroop, Anand/0000-0002-1975-1141
FU Ministerio de Educacion y Ciencia [BFU2006-04562]; CIBERER [U718];
Fundaluce ONCE; National Eye Institute, National Institutes of Health
FX Supported by grant BFU2006-04562 (Ministerio de Educacion y Ciencia),
CIBERER (U718), Fundaluce ONCE (RG-D), and an intramural program of the
National Eye Institute, National Institutes of Health (AS). JP is under
contract to CIBERER. EP is under contract to CIBERER.
NR 33
TC 26
Z9 27
U1 0
U2 1
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 MAY
PY 2010
VL 51
IS 5
BP 2656
EP 2663
DI 10.1167/iovs.09-4857
PG 8
WC Ophthalmology
SC Ophthalmology
GA 589UU
UT WOS:000277180500049
PM 20042663
ER
PT J
AU Laskey, WK
Feinendegen, LE
Neumann, RD
Dilsizian, V
AF Laskey, Warren K.
Feinendegen, Ludwig E.
Neumann, Ronald D.
Dilsizian, Vasken
TI Low-Level Ionizing Radiation From Noninvasive Cardiac Imaging: Can We
Extrapolate Estimated Risks From Epidemiologic Data to the Clinical
Setting?
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE radiation; imaging; risk
ID ATOMIC-BOMB SURVIVORS; CANCER-RISKS; EXPOSURE; MORTALITY; RESPONSES
AB Clinical decision-making regarding the use of low-level ionizing radiation for diagnostic and/or therapeutic purposes in patients with cardiovascular disease must, as in all other clinical scenarios, encompass the broad range of the risk-benefit ratio. Concerns regarding the late carcinogenic effects of exposure to low levels, i.e., <100 mSv, of ionizing radiation stem from extrapolation of exposure-outcome data in survivors of World War II atomic bomb explosions. However, ongoing debate regarding the true incremental risk to subjects exposed to doses currently administered in cardiovascular procedures fails to take into account the uncertainty of the dose-response relationship in this lower range, as well as tissue-specific reparative responses, also manifest at lower levels of exposure. The present discussion draws attention to both of these aspects as they relate to clinical decision-making. (J Am Coll Cardiol Img 2010;3:517-24) (C) 2010 by the American College of Cardiology Foundation
C1 [Laskey, Warren K.] Univ New Mexico, Sch Med, Dept Med, Albuquerque, NM 87131 USA.
[Feinendegen, Ludwig E.] Univ Dusseldorf, Dusseldorf, Germany.
[Feinendegen, Ludwig E.] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Neumann, Ronald D.] NIH, Dept Med Imaging, Ctr Clin, Bethesda, MD 20892 USA.
[Dilsizian, Vasken] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA.
RP Laskey, WK (reprint author), Univ New Mexico, Sch Med, Dept Med, MSC10-5550, Albuquerque, NM 87131 USA.
EM wlaskey@salud.unm.edu
NR 29
TC 26
Z9 26
U1 1
U2 1
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 MAY
PY 2010
VL 3
IS 5
BP 517
EP 524
DI 10.1016/j.jcmg.2009.11.017
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 647NW
UT WOS:000281626200009
PM 20466348
ER
PT J
AU Katz, IT
Shapiro, R
Li, D
Govindarajulu, U
Thompson, B
Watts, DH
Hughes, MD
Tuomala, R
AF Katz, Ingrid T.
Shapiro, Roger
Li, Daner
Govindarajulu, Usha
Thompson, Bruce
Watts, D. Heather
Hughes, Michael D.
Tuomala, Ruth
TI Risk Factors for Detectable HIV-1 RNA at Delivery Among Women Receiving
Highly Active Antiretroviral Therapy in the Women and Infants
Transmission Study
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE antiretrovirals; HIV; pregnancy; MTCT; HAART
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERINATAL TRANSMISSION; LOPINAVIR
EXPOSURE; VIRAL LOAD; PREGNANCY; NELFINAVIR; POSTPARTUM; ZIDOVUDINE;
INFECTION; ADHERENCE
AB Background: Detectable HIV-1 RNA at delivery is the strongest predictor of mother-to-child transmission. The risk factors for detectable HIV, including type of regimen, are unknown. We evaluated factors, including highly active antiretroviral (HAART) regimen, associated with detectable HIV-1 RNA at delivery in the Women and Infants Transmission Study (WITS).
Methods: Data from 630 HIV-1-infected women who enrolled from 1998 to 2005 and received HAART during pregnancy were analyzed. Multivariable analyses examined associations between regimens, demographic factors, and detectable HIV-1 RNA (>400 copies/milliliter) at delivery.
Results: Overall, 32% of the women in the cohort had detectable HIV-1 RNA at delivery. Among the subset of 364 HAART-experienced women, a lower CD4(+) cell count at enrollment [adjusted odds ratio (AOR) = 1.20 per 100 cells/mu L, confidence interval (CI) 1.04 to 1.37] and higher HIV-1 RNA at enrollment (AOR = 1.52 per log(10) copies/milliliter, CI 1.32 to 1.75) were significantly associated with detectable HIV-1 RNA levels at delivery. For the 266 HAART-naive women, both lower CD4(+) cell count at enrollment (AOR = 1.24 per 100 cells/mu L, CI 1.05 to 1.48) and higher HIV-1 RNA at enrollment (AOR = 1.35 per log(10) copies/milliliter, CI 1.12 to 1.63) were associated with detectable HIV-1 RNA at delivery. In addition, age at delivery (AOR = 0.92 per 10 years older, CI 0.86 to 0.99) and maternal illicit drug use (AOR = 3.15, CI 1.34 to 7.41) were significantly associated with detectable HIV-1 RNA at delivery among HAART-naive women. Type of HAART regimen was not significant in either group.
Conclusions: Lack of viral suppression at delivery was common in the WITS cohort, but differences by antiretroviral regimen were not identified. Despite a transmission rate below 1% in the last 5 years of the WITS cohort, improved measures to maximize HIV-1 RNA suppression at term among high-risk women are warranted.
C1 [Katz, Ingrid T.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02120 USA.
[Katz, Ingrid T.; Shapiro, Roger] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Katz, Ingrid T.; Shapiro, Roger; Govindarajulu, Usha] Harvard Univ, Sch Med, Boston, MA USA.
[Li, Daner; Thompson, Bruce] Clin Trials & Surveys Corp, Baltimore, MD USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,3rd Floor BWH, Boston, MA 02120 USA.
EM ikatz2@partners.org
FU Harvard Catalyst/The Harvard Clinical and Translational Science Center,
NIH [1KL2RR025757-01]; Harvard University; NIAID [AI 007433];
[4U01AI066454-0509]; [5U01AI068634-03]
FX Please see appendix for support information for individual
investigators. Ingrid Katz is currently funded via Harvard Catalyst/The
Harvard Clinical and Translational Science Center (NIH grant
#1KL2RR025757-01 and financial contributions from Harvard University and
its affiliated academic health centers). Additional funding includes the
following: Ingrid Katz (NIAID AI 007433); Roger Shapiro
(4U01AI066454-0509); and Michael Hughes (5U01AI068634-03).
NR 25
TC 21
Z9 22
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAY 1
PY 2010
VL 54
IS 1
BP 27
EP 34
DI 10.1097/QAI.0b013e3181caea89
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 587OG
UT WOS:000277001500004
PM 20065861
ER
PT J
AU Engels, EA
Pfeiffer, RM
Landgren, O
Moore, RD
AF Engels, Eric A.
Pfeiffer, Ruth M.
Landgren, Ola
Moore, Richard D.
TI Immunologic and Virologic Predictors of AIDS-Related Non-Hodgkin
Lymphoma in the Highly Active Antiretroviral Therapy Era
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE non-Hodgkin lymphoma; acquired immunodeficiency syndrome; human
immunodeficiency virus; immunosuppression; Epstein-Barr virus;
inflammation
ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-CELL ACTIVATION; UNITED-STATES; HIV
DISEASE; PEOPLE; CANCER; INFECTION; COHORT; RISK
AB HIV-infected persons treated with highly active antiretroviral therapy (HAART) continue to have elevated risk for non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of NHL among patients at an urban HIV clinic (N = 3025). Proportional hazards models identified immunologic and virologic predictors of NHL. Sixty-five NHLs arose during 1989 to 2006. NHL incidence declined over time. Nonetheless, 51 NHLs (78%) occurred within the HAART era (1996-2006). NHL risk increased with declining CD4 count (P trend < 0.0001) and increasing HIV viral load (P trend = 0.005). In a multivariable model, NHL risk was independently associated with both current CD4 count (hazard ratios 7.7 and 3.8, respectively, for CD4 counts 0-99 and 100-249 vs. 250+ cells/mm(3); P trend < 0.0001) and prior time spent with a viral load above 5.00 log(10) copies/mL (hazard ratios of 3.4, 2.6, and 6.8, respectively, for 0.1-0.4, 0.5-1.4, and 1.5+ yr vs. 0 yr; P trend = 0.004). Although serum globulin levels were elevated compared with the general population, NHL risk was unrelated to this B-cell activation marker (P = 0.39). Among HIV-infected individuals in the HAART era, NHLs are linked to immunosuppression and extended periods of uncontrolled HIV viremia. The association with high-level viremia could reflect detrimental effects on immune function related to incompletely effective HAART or direct effects on B cells.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Rockville, MD 20892 USA.
[Engels, Eric A.; Moore, Richard D.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Landgren, Ola] NCI, Ctr Canc Res, Rockville, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA.
EM engelse@exchange.nih.gov
FU National Cancer Institute; National Institutes of Health [R01 DA11602,
R01 AA16893, K24 DA00432]
FX This study was supported by the Intramural Research Program of the
National Cancer Institute, and by National Institutes of Health grants
R01 DA11602, R01 AA16893, and K24 DA00432.
NR 29
TC 42
Z9 45
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAY 1
PY 2010
VL 54
IS 1
BP 78
EP 84
DI 10.1097/01.qai.0000371677.48743.8d
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 587OG
UT WOS:000277001500011
PM 20418723
ER
PT J
AU Hollingsworth, JW
Free, ME
Li, ZW
Andrews, LN
Nakano, H
Cook, DN
AF Hollingsworth, John W.
Free, Meghan E.
Li, Zhuowei
Andrews, Laura Novack
Nakano, Hideki
Cook, Donald N.
TI Ozone activates pulmonary dendritic cells and promotes allergic
sensitization through a Toll-like receptor 4-dependent mechanism
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID ANTIGEN; IL-10; B7-1; MICE
C1 [Hollingsworth, John W.; Li, Zhuowei] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27706 USA.
[Free, Meghan E.; Andrews, Laura Novack; Nakano, Hideki; Cook, Donald N.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Hollingsworth, JW (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27706 USA.
EM cookd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102025-04]; NIEHS NIH HHS [ES16659, ES16126,
R01 ES016126, R21 ES016659]
NR 14
TC 17
Z9 17
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAY
PY 2010
VL 125
IS 5
BP 1167
EP 1170
DI 10.1016/j.jaci.2010.03.001
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 596LO
UT WOS:000277686700033
PM 20394980
ER
PT J
AU Zhai, B
Zhou, H
Yang, LP
Zhang, J
Jung, K
Giam, CZ
Xiang, X
Lin, XR
AF Zhai, Bing
Zhou, Henry
Yang, Liangpeng
Zhang, Jun
Jung, Kathy
Giam, Chou-Zen
Xiang, Xin
Lin, Xiaorong
TI Polymyxin B, in combination with fluconazole, exerts a potent fungicidal
effect
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
DE antifungal; combination therapy; antibiotic; fungal membrane
ID GRAM-NEGATIVE BACTERIA; ACINETOBACTER-BAUMANNII MENINGITIS;
SUSCEPTIBILITY TESTING METHODS; VAR. GRUBII SEROTYPE;
CRYPTOCOCCUS-NEOFORMANS; ANTIMICROBIAL PEPTIDE;
SACCHAROMYCES-CEREVISIAE; ASPERGILLUS-FUMIGATUS; INTRAVENOUS COLISTIN;
ANTIFUNGAL AGENTS
AB The objective of this study was to identify existing clinical compounds that either possess a fungicidal activity alone or can act synergistically with fungistatic antifungals.
We screened a clinical compound library for drugs that exhibited anti-Aspergillus activity. Among selected compounds, the cationic peptide antibiotic polymyxin B was chosen for further characterization because it can be used parenterally and topically. The fungicidal effect of polymyxin B and its synergistic interactions with azole antifungals were tested against a variety of fungal species. The toxicity of the drug combination of polymyxin B and fluconazole was compared with that of each drug alone in mammalian cell cultures.
We found that polymyxin B possesses a broad-spectrum antifungal activity at relatively high concentrations. However, because of its synergistic interactions with azole antifungals, polymyxin B at much lower concentrations exerts a potent fungicidal effect against Cryptococcus neoformans, Candida albicans and non-albicans Candida species and moulds when combined with azoles. The combination of polymyxin B and fluconazole at concentrations within susceptible breakpoints is particularly potent against C. neoformans isolates, including fluconazole-resistant strains. The drug combination displayed no additional toxicity compared with polymyxin B alone when tested in cell culture.
The combination of polymyxin B and fluconazole has the potential to be used in the clinic to treat systemic cryptococcosis. Our findings suggest that combining cationic peptide antibiotics with azole antifungals could provide a new direction for developing novel antifungal therapies.
C1 [Zhai, Bing; Lin, Xiaorong] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA.
[Zhou, Henry; Zhang, Jun; Xiang, Xin] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
[Yang, Liangpeng; Giam, Chou-Zen] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Jung, Kathy] NIAAA, Rockville, MD 20852 USA.
RP Lin, XR (reprint author), Texas A&M Univ, Dept Biol, 3258 TAMU, College Stn, TX 77843 USA.
EM xlin@mail.bio.tamu.edu
FU Department of Biology of Texas AM University; CNP Department of Defense
[G171IM]; National Institutes of Health [GM069527, CA115884]
FX This work was supported by: the Department of Biology of Texas A&M
University (the startup fund to X. L.); CNP Department of Defense (grant
G171IM to X. X.); and National Institutes of Health (grant numbers
GM069527 to X. X. and CA115884 to C.-Z. G.).
NR 73
TC 34
Z9 36
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD MAY
PY 2010
VL 65
IS 5
BP 931
EP 938
DI 10.1093/jac/dkq046
PG 8
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 581ML
UT WOS:000276527500016
PM 20167587
ER
PT J
AU Xu, S
Galperin, M
Melvin, G
Horowits, R
Raben, N
Plotz, P
Yu, L
AF Xu, Sengen
Galperin, Mikhail
Melvin, Gary
Horowits, Robert
Raben, Nina
Plotz, Paul
Yu, Leepo
TI Impaired organization and function of myofilaments in single muscle
fibers from a mouse model of Pompe disease
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE lysosomal glycogen storage disease; actin-myosin interaction
ID GLUCOSIDASE KNOCKOUT MICE; X-RAY-DIFFRACTION; LYSOSOMAL STORAGE DISEASE;
RABBIT PSOAS MUSCLE; SKELETAL-MUSCLE; GLYCOGEN-STORAGE; NONCONTRACTILE
INCLUSIONS; PARALLEL INHIBITION; FORCE GENERATION; IONIC-STRENGTH
AB Xu S, Galperin M, Melvin G, Horowits R, Raben N, Plotz P, Yu LC. Impaired organization and function of myofilaments in single muscle fibers from a mouse model of Pompe disease. J Appl Physiol 108: 1383-1388, 2010. First published March 11, 2010; doi: 10.1152/japplphysiol. 01253.2009.-Pompe disease, a deficiency of lysosomal acid alpha-glucosidase, is a disorder of glycogen metabolism that can affect infants, children, or adults. In all forms of the disease, there is progressive muscle pathology leading to premature death. The pathology is characterized by accumulation of glycogen in lysosomes, autophagic buildup, and muscle atrophy. The purpose of the present investigation was to determine if myofibrillar dysfunction in Pompe disease contributes to muscle weakness beyond that attributed to atrophy. The study was performed on isolated myofibers dissected from severely affected fast glycolytic muscle in the alpha-glucosidase knockout mouse model. Psoas muscle fibers were first permeabilized, so that the contractile proteins could be directly relaxed or activated by control of the composition of the bathing solution. When normalized by cross-sectional area, single fibers from knockout mice produced 6.3 N/cm(2) of maximum Ca(2+) -activated tension compared with 12.0 N/cm(2) produced by wild-type fibers. The total protein concentration was slightly higher in the knockout mice, but concentrations of the contractile proteins myosin and actin remained unchanged. Structurally, X-ray diffraction showed that the actin and myosin filaments, normally arranged in hexagonal arrays, were disordered in the knockout muscle, and a lower fraction of myosin cross bridges was near the actin filaments in the relaxed muscle. The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers.
C1 [Xu, Sengen; Galperin, Mikhail; Melvin, Gary; Horowits, Robert; Raben, Nina; Plotz, Paul; Yu, Leepo] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Yu, L (reprint author), NIAMSD, NIH, Bldg 50,Rm 1531,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yule@mail.nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
NR 31
TC 11
Z9 12
U1 0
U2 1
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 MAY
PY 2010
VL 108
IS 5
BP 1383
EP 1388
DI 10.1152/japplphysiol.01253.2009
PG 6
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 591LB
UT WOS:000277301000045
PM 20223998
ER
PT J
AU Piersanti, S
Remoli, C
Saggio, I
Funari, A
Michienzi, S
Sacchetti, B
Robey, PG
Riminucci, M
Bianco, P
AF Piersanti, Stefania
Remoli, Cristina
Saggio, Isabella
Funari, Alessia
Michienzi, Stefano
Sacchetti, Benedetto
Robey, Pamela Gehron
Riminucci, Mara
Bianco, Paolo
TI Transfer, Analysis, and Reversion of the Fibrous Dysplasia Cellular
Phenotype in Human Skeletal Progenitors
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE FIBROUS DYSPLASIA; STROMAL CELLS; LENTIVIRAL VECTORS; SKELETAL
PROGENITORS
ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; FRTL-5 THYROID-CELLS;
ACTIVE GS-ALPHA; STEM-CELLS; ACTIVATING MUTATIONS; RNA INTERFERENCE;
IN-VIVO; ADIPOCYTE DIFFERENTIATION; ADENYLYL-CYCLASE
AB Human skeletal progenitors were engineered to stably express R201C mutated, constitutively active Gs alpha using lentiviral vectors. Longterm transduced skeletal progenitors were characterized by an enhanced production of cAMP, indicating the transfer of the fundamental cellular phenotype caused by activating mutations of Gs alpha. Like skeletal progenitors isolated from natural fibrous dysplasia (FD) lesions, transduced cells could generate bone but not adipocytes or the hematopoietic microenvironment on in vivo transplantation. In vitro osteogenic differentiation was noted for the lack of mineral deposition, a blunted upregulation of osteocalcin, and enhanced upregulation of other osteogenic markers such as alkaline phosphatase (ALP) and bone sialoprotein (BSP) compared with controls. A very potent upregulation of RANKL expression was observed, which correlates with the pronounced osteoclastogenesis observed in FD lesions in vivo. Stable transduction resulted in a marked upregulation of selected phosphodiesterase (PDE) isoform mRNAs and a prominent increase in total PDE activity. This predicts an adaptive response in skeletal progenitors transduced with constitutively active, mutated Gs alpha. Indeed, like measurable cAMP levels, the differentiative responses of transduced skeletal progenitors were profoundly affected by inhibition of PDEs or lack thereof. Finally, using lentiviral vectors encoding short hairpin (sh) RNA interfering sequences, we demonstrated that selective silencing of the mutated allele is both feasible and effective in reverting the aberrant cAMP production brought about by the constitutively active Gs alpha and some of its effects on in vitro differentiation of skeletal progenitors. (C) 2010 American Society for Bone and Mineral Research.
C1 [Remoli, Cristina; Funari, Alessia; Michienzi, Stefano; Sacchetti, Benedetto; Riminucci, Mara; Bianco, Paolo] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy.
[Piersanti, Stefania; Remoli, Cristina; Saggio, Isabella; Funari, Alessia; Michienzi, Stefano; Sacchetti, Benedetto; Riminucci, Mara; Bianco, Paolo] Biomed Sci Pk San Raffaele, Rome, Italy.
[Piersanti, Stefania; Saggio, Isabella] Univ Roma La Sapienza, Dept Genet & Mol Biol, I-00161 Rome, Italy.
[Saggio, Isabella] CNR, Inst Mol Biol & Pathol, Rome, Italy.
[Robey, Pamela Gehron] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD USA.
RP Bianco, P (reprint author), Univ Roma La Sapienza, Dept Expt Med, Viale Regina Elena 324, I-00161 Rome, Italy.
EM paolo.bianco@uniroma1.it
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; saggio, isabella/0000-0002-9497-7415
FU Telethon Italy [GGP09227]; Fondazione Roma
FX The financial support of Telethon Italy (Grant GGP09227) and Fondazione
Roma is gratefully acknowledged.
NR 43
TC 35
Z9 35
U1 1
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2010
VL 25
IS 5
BP 1103
EP 1116
DI 10.1359/jbmr.091036
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 604PX
UT WOS:000278292100021
PM 19874199
ER
PT J
AU Romanova, LY
Holmes, G
Bahte, SK
Kovalchuk, AL
Nelson, PJ
Ward, Y
Gueler, F
Mushinski, JF
AF Romanova, Larisa Y.
Holmes, Gibran
Bahte, Svenja K.
Kovalchuk, Alexander L.
Nelson, Patrick J.
Ward, Yvona
Gueler, Faikah
Mushinski, J. Frederic
TI Phosphorylation of paxillin at threonine 538 by PKC delta regulates
LFA1-mediated adhesion of lymphoid cells
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Paxillin; Threonine phosphorylation; Lymphocytes; LFA-1
ID PROTEIN-KINASE-C; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; INTEGRIN
FUNCTION; ACTIVATION; MEMBRANE; DOMAINS; AVIDITY; BINDING; ALPHA
AB We investigated the PKC delta-mediated phosphorylation of paxillin within its LIM4 domain and the involvement of this phosphorylation in activation of LFA-1 integrins of the Baf3 pro-B lymphocytic cell line. Using phosphorylated-threonine-specific antibodies, phosphorylated amino acid analysis and paxillin phosphorylation mutants, we demonstrated that TPA, the pharmacological analog of the endogenous second messenger diacyl glycerol, stimulates paxillin phosphorylation at threonine 538 (T538). The TPA-responsive PKC isoform PKC delta directly binds paxillin in a yeast two-hybrid assay and phosphorylates paxillin at T538 in vitro and also co-immunoprecipitates with paxillin and mediates phosphorylation of this residue in vivo. Recombinant wild-type paxillin, its phospho-inhibitory T538A or phospho-mimetic T538E mutants were expressed in the cells simultaneously with siRNA silencing of the endogenous paxillin. These experiments suggest that phosphorylation of paxillin T538 contributes to dissolution of the actin cytoskeleton, redistribution of LFA-1 integrins and an increase in their affinity. We also show that phosphorylation of T538 is involved in the activation of LFA-1 integrins by TPA.
C1 [Romanova, Larisa Y.; Holmes, Gibran; Nelson, Patrick J.; Mushinski, J. Frederic] NCI, Lab Canc Biol & Genet, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
[Bahte, Svenja K.; Gueler, Faikah] Hannover Med Sch, Dept Nephrol, D-30625 Hannover, Germany.
[Kovalchuk, Alexander L.] NIAID, Immunopathol Lab, NIH, Rockville, MD 20854 USA.
[Ward, Yvona] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Romanova, LY (reprint author), NCI, Lab Canc Biol & Genet, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
EM romanovl@dc37a.nci.nih.gov
FU NIH; National Cancer Institute; National Institute of Allergy and
Infectious Diseases
FX This research was supported in part by the Intramural Research Program
of the NIH, the National Cancer Institute and the National Institute of
Allergy and Infectious Diseases. The authors thank Stephen Shaw for
helpful discussions and pre-publication access to his PKC motif data,
Harald Mischak of Hannover Medical School and Mosaiques Diagnostics &
Therapeutics AG for his generous gift of purified PKC., and Kee-Oh Chay
for sharing his data on paxillin radiolabeling. We also thank Scott
vande Pol for providing the LIM-1-deficient paxillin constructs and Igor
Elman for statistical analysis. Deposited in PMC for release after 12
months.
NR 37
TC 9
Z9 9
U1 0
U2 1
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 MAY 1
PY 2010
VL 123
IS 9
BP 1567
EP 1577
DI 10.1242/jcs.060996
PG 11
WC Cell Biology
SC Cell Biology
GA 586MA
UT WOS:000276912300021
PM 20388733
ER
PT J
AU Bao, JJ
Lu, ZP
Joseph, JJ
Carabenciov, D
Dimond, CC
Pang, LY
Samsel, L
Mccoy, JP
Leclerc, J
Nguyen, P
Gius, D
Sack, MN
AF Bao, Jianjun
Lu, Zhongping
Joseph, Joshua J.
Carabenciov, Darin
Dimond, Christopher C.
Pang, Liyan
Samsel, Leigh
Mccoy, J. Philip, Jr.
Leclerc, Jaime
Nguyen, PhuongMai
Gius, David
Sack, Michael N.
TI Characterization of the Murine SIRT3 Mitochondrial Localization Sequence
and Comparison of Mitochondrial Enrichment and Deacetylase Activity of
Long and Short SIRT3 Isoforms
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE SIRT3; MITOCHONDRIAL PROTEIN DEACETYLATION; MITOCHONDRIAL LOCALIZATION
SEQUENCE; NUCLEAR LOCALIZATION
ID LYSINE ACETYLATION; DEPENDENT DEACETYLASE; MOUSE SIRT3; SIRTUINS;
HOMOLOG; PROTEINS; GENE; PRESEQUENCES; REGULATOR; STRESS
AB SIRT3 is identified as the major mitochondrial deacetylase. Two distinct isoforms of the murine SIRT3 have been identified with the short isoform having no recognizable mitochondrial localization sequence (MLS) and the long isoform having a putative MLS. A recent study questions the mitochondrial deacetylase activity of this short isoform. In contrast, the long isoform has been shown to be predominantly mitochondrial with robust deacetylase activity. In this study, we investigate whether the amino-terminus of the long SIRT3 isoform is a legitimate MLS and evaluate in-situ mitochondrial deacetylase activity of both isoforms. We confirm the presence of long and short isoforms in murine liver and kidney. The long isoform is generated via intra-exon splicing creating a frame-shift to expose a novel upstream translation start site. Mitochondrial localization is significantly more robust following transfection of the long compared with the short isoform. Insertion of this alternatively spliced novel 5' sequence upstream of a GFP-reporter plasmid shows greater than 80% enrichment in mitochondria, confirming this region as a legitimate mitochondrial localization sequence. Despite lower mitochondrial expression of the short isoform, the capacity to deacetylate mitochondria proteins and to restore mitochondrial respiration is equally robust following transient transfection of either isoform into SIRT3 knockout embryonic fibroblasts. How these alternative transcripts are regulated and whether they modulate distinct targets is unknown. Furthermore, in contrast to exclusive mitochondria enrichment of endogenous SIRT3, overexpression of both isoforms shows nuclear localization. This overexpression effect, may partially account for previously observed divergent phenotypes attributed to SIRT3. J. Cell. Biochem. 110: 238-247, 2010. Published 2010 Wiley-Liss, Inc.(dagger)
C1 [Bao, Jianjun; Lu, Zhongping; Joseph, Joshua J.; Carabenciov, Darin; Dimond, Christopher C.; Pang, Liyan; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Leclerc, Jaime; Nguyen, PhuongMai; Gius, David] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), Bld 10-CRC,Room 5-3150,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
FU Divisions of Intramural Research of the NHBLI; NCI of the National
Institutes of Health, Bethesda, MD, USA
FX Grant sponsor: Divisions of Intramural Research of the NHBLI; Grant
sponsor: NCI of the National Institutes of Health, Bethesda, MD, USA.
NR 31
TC 52
Z9 54
U1 1
U2 11
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD MAY 1
PY 2010
VL 110
IS 1
BP 238
EP 247
DI 10.1002/jcb.22531
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 593CO
UT WOS:000277429700026
PM 20235147
ER
PT J
AU Singh, SR
Zheng, ZY
Wang, H
Oh, SW
Chen, X
Hou, SX
AF Singh, Shree Ram
Zheng, Zhiyu
Wang, Hong
Oh, Su-Wan
Chen, Xiu
Hou, Steven X.
TI Competitiveness for the Niche and Mutual Dependence of the Germline and
Somatic Stem Cells in the Drosophila Testis Are Regulated by the
JAK/STAT Signaling
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID SELF-RENEWAL; JAK-STAT; SUPPORT CELLS; TUMOR-SUPPRESSOR; OVARY; PATHWAY;
SPERMATOGENESIS; MAINTENANCE; DIFFERENTIATION; PROTEIN
AB In many tissues, two or more types of stem cells share a niche, and how the stem cells coordinate their self-renewal and differentiation is poorly understood. In the Drosophila testis, germ line stem cells (GSCs) and somatic cyst progenitor cells (CPCs) contact each other and share a niche (the hub). The hub expresses a growth factor unpaired (Upd) that activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in GSCs to regulate the stem cell self-renewal. Here, we demonstrate that the JAK/STAT signaling also regulates CPCs self-renewal. We also show that a negative regulator, the suppressor of cytokine signaling 36E (SOCS36E), suppresses JAK/STAT signaling in somatic cells, preventing them from out-competing the GSCs. Furthermore, through selectively manipulating the JAK/STAT signaling level in either CPCs or GSCs, we demonstrate that the somatic JAK/STAT signaling is essential for self-renewal and maintenance of both CPCs and GSCs. These data suggest that a single JAK/STAT signal from the niche orchestrate the competitive and dependent co-existence of GSCs and CPCs in the Drosophila testis niche. J. Cell. Physiol. 223: 500-510, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Singh, Shree Ram; Zheng, Zhiyu; Wang, Hong; Oh, Su-Wan; Chen, Xiu; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
EM singhshr@mail.nih.gov; shou@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU NIH; National Cancer Institute
FX We thank B. Mathey-Prevot, T. Xie, S. DiNardo, C. Dearolf, and the
Bloomington stock center for fly stocks; D. Godt, R. Lehmann, and the
Developmental Study Hybridoma Bank for antibodies; Stephen Lockett for
help on confocal microscope; N. Parrish for help on preparation of the
manuscript. This research was supported by the Intramural Research
Program of NIH, National Cancer Institute.
NR 72
TC 29
Z9 29
U1 1
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD MAY
PY 2010
VL 223
IS 2
BP 500
EP 510
DI 10.1002/jcp.22073
PG 11
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 580DV
UT WOS:000276428100026
PM 20143337
ER
PT J
AU Segars, JH
DeCherney, AH
AF Segars, James H.
DeCherney, Alan H.
TI Is There a Genetic Basis for Polycystic Ovary Syndrome?
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Editorial Material
ID EXTRACELLULAR-MATRIX; CHROMOSOME 19P13.2; SUSCEPTIBILITY; FIBRILLIN-3;
ASSOCIATION; FOLLISTATIN; LINKAGE; DISEASE; REGION; HEALTH
C1 [Segars, James H.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Bldg 10,CRC,Room 1E3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
NR 17
TC 6
Z9 6
U1 1
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 MAY
PY 2010
VL 95
IS 5
BP 2058
EP 2060
DI 10.1210/jc.2010-0518
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 592DW
UT WOS:000277356700007
PM 20444933
ER
PT J
AU Nader, N
Bachrach, BE
Hurt, DE
Gajula, S
Pittman, A
Lescher, R
Kino, T
AF Nader, Nancy
Bachrach, Bert E.
Hurt, Darrell E.
Gajula, Sonia
Pittman, Amy
Lescher, Rachel
Kino, Tomoshige
TI A Novel Point Mutation in Helix 10 of the Human Glucocorticoid Receptor
Causes Generalized Glucocorticoid Resistance by Disrupting the Structure
of the Ligand-Binding Domain
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
AB Context: Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by partial insensitivity to glucocorticoids, caused by mutations in the glucocorticoid receptor (GR) gene. Most of the reported cases are adults, demonstrating symptoms associated with mineralocorticoid and/or adrenal androgen excess caused by compensatively increased secretion of the adrenocorticotropic hormone.
Patient: We identified a new 2-yr-old female case of generalized glucocorticoid resistance syndrome. The patient (TJ) presented with a generalized seizure associated with hypoglycemia and hypokalemia. She also had hypertension and premature pubarche, whereas dexamethasone effectively suppressed these clinical manifestations.
Results: The patient's GR gene had a heterozygotic mutation (G -> A) at nucleotide position 2141 (exon 8), which resulted in substitution of arginine by glutamine at amino acid position 714 in the ligand-binding domain (LBD) of the GR alpha. Molecular analysis revealed that the mutant receptor had significantly impaired transactivation activity with a 2-fold reduction in affinity to ligand. It showed attenuated transactivation of the activation function (AF)-2 and reduced binding to a p160 nuclear receptor coactivator. Computer-based structural analysis revealed that replacement of arginine by glutamine at position 714 transmitted a conformational change to the LBD and the AF-2 transactivation surface, resulting in a decreased binding affinity to ligand and to the LXXLL coactivator motif.
Conclusions: Dexamethasone treatment is effective in controlling the premature pubarche, hypoglycemia, hypertension, and hypokalemia in this child case, wherein arginine 714 plays a key role in the proper formation of the ligand-binding pocket and the AF-2 surface of the GR alpha LBD. (J Clin Endocrinol Metab 95: 2281-2285, 2010)
C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bethesda, MD 20892 USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Bachrach, Bert E.; Gajula, Sonia; Pittman, Amy; Lescher, Rachel] Univ Missouri, Childrens Hosp, Dept Pediat Endocrinol Diabet, Columbia, MO 65212 USA.
RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bldg 10,Room 1E-3140,10 Ctr Dr MSC1109, Bethesda, MD 20892 USA.
EM kinot@mail.nih.gov
RI Hurt, Darrell/B-5076-2013
OI Hurt, Darrell/0000-0002-9829-8567
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 9
TC 22
Z9 23
U1 0
U2 2
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 MAY
PY 2010
VL 95
IS 5
BP 2281
EP 2285
DI 10.1210/jc.2009-2463
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 592DW
UT WOS:000277356700038
PM 20335448
ER
PT J
AU Ewens, KG
Stewart, DR
Ankener, W
Urbanek, M
McAllister, JM
Chen, C
Baig, KM
Parker, SCJ
Margulies, EH
Legro, RS
Dunaif, A
Strauss, JF
Spielman, RS
AF Ewens, Kathryn G.
Stewart, Douglas R.
Ankener, Wendy
Urbanek, Margrit
McAllister, Jan M.
Chen, Chen
Baig, K. Maravet
Parker, Stephen C. J.
Margulies, Elliot H.
Legro, Richard S.
Dunaif, Andrea
Strauss, Jerome F., III
Spielman, Richard S.
TI Family-Based Analysis of Candidate Genes for Polycystic Ovary Syndrome
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GROWTH-FACTOR-BETA; THECA CELLS; CHROMOSOME 19P13.2; FIBRILLIN-3;
ASSOCIATION; FOLLISTATIN; EXPRESSION; PHENOTYPE; PROTEIN; SUSCEPTIBILITY
AB Context: Polycystic ovary syndrome (PCOS) is a complex disorder having both genetic and environmental components. A number of association studies based on candidate genes have reported significant association, but few have been replicated. D19S884, a polymorphic marker in fibrillin 3 (FBN3), is one of the few association findings that has been replicated in independent sets of families.
Objective: The aims of the study are: 1) to genotype single nucleotide polymorphisms (SNPs) in the region of D19S884; and 2) to follow up with an independent data set, published results reporting evidence for PCOS candidate gene associations.
Design: The transmission disequilibrium test (TDT) was used to analyze linkage and association between PCOS and SNPs in candidate genes previously reported by us and by others as significantly associated with PCOS.
Setting: The study was conducted at academic medical centers.
Patients or Other Participants: A total of 453 families having a proband with PCOS participated in the study. Sisters with PCOS were also included. There was a total of 502 probands and sisters with PCOS.
Intervention(s): There were no interventions.
Main Outcome Measure(s): The outcome measure was transmission frequency of SNP alleles.
Results: We identified a six-SNP haplotype block spanning a 6.7-kb region on chromosome 19p13.2 that includes D19S884. SNP haplotype allele-C alone and in combination with D19S884-allele 8 is significantly associated with PCOS: haplotype-C TDT chi(2) = 10.0 (P = 0.0016) and haplotype-C/A8 TDT chi(2) = 7.6 (P = 0.006). SNPs in four of the other 26 putative candidate genes that were tested using the TDT were nominally significant (ACVR2A, POMC, FEM1B, and SGTA). One SNP in POMC (rs12473543, chi(2) = 9.1; P(corrected) = 0.042) is significant after correction for multiple testing.
Conclusions: A polymorphic variant, D19S884, in FBN3 is associated with risk of PCOS. POMC is also a candidate gene of interest. (J Clin Endocrinol Metab 95: 2306-2315, 2010)
C1 [Ewens, Kathryn G.; Ankener, Wendy; Spielman, Richard S.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Stewart, Douglas R.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Urbanek, Margrit; Dunaif, Andrea] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[McAllister, Jan M.] Penn State Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA.
[Chen, Chen; Baig, K. Maravet; Strauss, Jerome F., III] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA 23298 USA.
[Parker, Stephen C. J.; Margulies, Elliot H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Legro, Richard S.] Penn State Hershey Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA.
RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Dept Obstet & Gynecol 7628, Med Coll Virginia Campus, Richmond, VA 23298 USA.
EM jfstrauss@vcu.edu
FU National Institutes of Health (NIH) [U54HD034449]; Division of
Intramural Research of the National Human Genome Research Institute; NIH
[5R01HD033852, 5R01HD058300, P50 HD44405, U54 HD34449, RR10732, C06
RR016499]; Virginia Commonwealth University School of Medicine [M01
RR00048, M01 RR10732, M01 RR02635]
FX This research was supported by National Institutes of Health (NIH)
Grants U54HD034449 (to J.F.S. and R.S.S.); the Division of Intramural
Research of the National Human Genome Research Institute (to D.R.S.);
NIH Grants 5R01HD033852, 5R01HD058300 (to J.M.M.), P50 HD44405 (to M. U.
and A. D.), U54 HD34449 (to A. D.), RR10732 and C06 RR016499 [to
Pennsylvania State University General Clinical Research Center (GCRC)],
M01 RR00048 (to Northwestern University GCRC), M01 RR10732, and M01
RR02635 (to Brigham and Women's Hospital GCRC). K. M. B. is supported by
the Physician Scientist training Program of Virginia Commonwealth
University School of Medicine.
NR 38
TC 65
Z9 66
U1 2
U2 7
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 MAY
PY 2010
VL 95
IS 5
BP 2306
EP 2315
DI 10.1210/jc.2009-2703
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 592DW
UT WOS:000277356700041
PM 20200332
ER
PT J
AU Koma, T
Yoshimatsu, K
Pini, N
Safronetz, D
Taruishi, M
Levis, S
Endo, R
Shimizu, K
Yasuda, SP
Ebihara, H
Feldmann, H
Enria, D
Arikawa, J
AF Koma, Takaaki
Yoshimatsu, Kumiko
Pini, Noemi
Safronetz, David
Taruishi, Midori
Levis, Silvana
Endo, Rika
Shimizu, Kenta
Yasuda, Shumpei P.
Ebihara, Hideki
Feldmann, Heinz
Enria, Delia
Arikawa, Jiro
TI Truncated Hantavirus Nucleocapsid Proteins for Serotyping Sin Nombre,
Andes, and Laguna Negra Hantavirus Infections in Humans and Rodents
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID MOUSE PEROMYSCUS-MANICULATUS; HUMORAL IMMUNE-RESPONSES; TO-PERSON
TRANSMISSION; MAJOR ANTIGENIC DOMAIN; RENAL SYNDROME HFRS; PULMONARY
SYNDROME; HEMORRHAGIC-FEVER; CARDIOPULMONARY SYNDROME; RECOMBINANT
BACULOVIRUS; MONOCLONAL-ANTIBODIES
AB Sin Nombre virus (SNV), Andes virus (ANDV), and Laguna Negra virus (LANV) have been known as the dominant causative agents of hantavirus pulmonary syndrome (HPS). ANDV and LANV, with different patterns of pathogenicity, exist in a sympatric relationship. Moreover, there is documented evidence of person-to-person transmission of ANDV. Therefore, it is important in clinical medicine and epidemiology to know the serotype of a hantavirus causing infection. Truncated SNV, ANDV, and LANV recombinant nucleocapsid proteins (trNs) missing 99 N-terminal amino acids (trN100) were expressed using a baculovirus system, and their applicability for serotyping SNV, ANDV, and LANV infection by the use of enzyme-linked immunosorbent assays (ELISA) was examined. HPS patient sera and natural-reservoir rodent sera infected with SNV, ANDV, and LANV showed the highest optical density (OD) values for homologous trN100 antigens. Since even patient sera with lower IgM and IgG antibody titers were serotyped, the trN100s are therefore considered useful for serotyping with early-acute-phase sera. In contrast, assays testing whole recombinant nucleocapsid protein antigens of SNV, ANDV, and LANV expressed in Escherichia coli detected homologous and heterologous antibodies equally. These results indicated that a screening ELISA using an E. coli-expressed antigen followed by a serotyping ELISA using trN100s is useful for epidemiological surveillance in regions where two or more hantavirus species cocirculate.
C1 [Koma, Takaaki; Yoshimatsu, Kumiko; Taruishi, Midori; Endo, Rika; Shimizu, Kenta; Yasuda, Shumpei P.; Arikawa, Jiro] Hokkaido Univ, Grad Sch Med, Dept Microbiol, Sapporo, Hokkaido 0608638, Japan.
[Pini, Noemi; Levis, Silvana; Enria, Delia] Inst Nacl Enfermedades Vigrales Humanas Dr Julio, Pergamino, Argentina.
[Safronetz, David; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
RP Arikawa, J (reprint author), Hokkaido Univ, Grad Sch Med, Dept Microbiol, Sapporo, Hokkaido 0608638, Japan.
EM j_arika@med.hokudai.ac.jp
RI Shimizu, Kenta/A-5259-2012; Yoshimatsu, Kumiko/D-9053-2012; Arikawa,
Jiro/D-9858-2012
FU Japanese Ministry of Education, Culture, Sports, Science and Technology;
Japanese Ministry of Health, Labor and Welfare [200829018A]; Founding
Research Centers for Emerging and Reemerging Infectious Diseases, MEXT,
Japan
FX This work was supported by the Global COE program Establishment of
International Collaboration Center for Zoonosis Control from the
Japanese Ministry of Education, Culture, Sports, Science and Technology.
This work was also partially supported by Grants-in-Aid for Scientific
Research and the Development of Scientific Research from the Japanese
Ministry of Health, Labor and Welfare (grant 200829018A). This study was
supported in part by the Program of Founding Research Centers for
Emerging and Reemerging Infectious Diseases, MEXT, Japan.
NR 36
TC 14
Z9 14
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2010
VL 48
IS 5
BP 1635
EP 1642
DI 10.1128/JCM.00072-10
PG 8
WC Microbiology
SC Microbiology
GA 592DV
UT WOS:000277356600019
PM 20335425
ER
PT J
AU Maurya, R
Mehrotra, S
Prajapati, VK
Nylen, S
Sacks, D
Sundar, S
AF Maurya, Radheshyam
Mehrotra, Sanjana
Prajapati, Vijay Kumar
Nylen, Susanne
Sacks, David
Sundar, Shyam
TI Evaluation of Blood Agar Microtiter Plates for Culturing Leishmania
Parasites To Titrate Parasite Burden in Spleen and Peripheral Blood of
Patients with Visceral Leishmaniasis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID DIAGNOSIS; INFECTION
AB Serial dilution of blood and spleen biopsy specimens, plated on Novy-MacNeal-Nicolle (NNN) blood agar using microtiter culture plates, is a sensitive and reproducible method for detection and growth of Leishmania parasites. Plates could be easily monitored, and growth could be rapidly detected. Moreover, parasite number may be estimated using this technique.
C1 [Maurya, Radheshyam; Mehrotra, Sanjana; Prajapati, Vijay Kumar; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Dept Med, Infect Dis Res Lab, Varanasi 221005, Uttar Pradesh, India.
[Nylen, Susanne; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Maurya, Radheshyam] Univ Hyderabad, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India.
RP Sundar, S (reprint author), Banaras Hindu Univ, Inst Med Sci, Dept Med, Infect Dis Res Lab, Varanasi 221005, Uttar Pradesh, India.
EM drshyamsundar@hotmail.com
OI Nylen, Susanne/0000-0002-3875-3353
FU NIAID, NIH, USA [1P50AI074321]; CSIR; ICMR, New Delhi, India
FX This work was supported by the Extramural Research Program of the NIAID,
NIH, USA grant number 1P50AI074321. S. M. and V. K. P. were funded by
CSIR and ICMR, New Delhi, India, respectively.
NR 11
TC 24
Z9 25
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2010
VL 48
IS 5
BP 1932
EP 1934
DI 10.1128/JCM.01733-09
PG 3
WC Microbiology
SC Microbiology
GA 592DV
UT WOS:000277356600073
PM 20335419
ER
PT J
AU Cardone, A
Albers, RW
Sriram, RD
Pant, HC
AF Cardone, Antonio
Albers, R. Wayne
Sriram, Ram D.
Pant, Harish C.
TI Evaluation of the Interaction of Cyclin-Dependent Kinase 5 with
Activator p25 and with p25-Derived Inhibitor CIP
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE computational geometry; cyclin-dependent kinase; feature-based shape
similarity assessment; neurodegenerative diseases; protein
phosphorylation
ID PROTEIN-PROTEIN DOCKING; MOLECULAR-DYNAMICS; LIGAND DOCKING; SHAPE
COMPLEMENTARITY; AUTOMATED DOCKING; MONTE-CARLO; ALGORITHMS; CONGRUENCE;
SIMULATION; MECHANISMS
AB A high-affinity inhibitor protein called CIP, produced by small truncations of p35, was experimentally identified. P35 is a physiological activator of the cyclin-dependent kinase cdk5. P25 is derived from proteolytic truncation of p35 within "stressed" neurons, and it is associated with the hyperphosphorylation of specific neuronal proteins, typically occurring in neurodegenerative diseases such as Alzheimer's. Here, we report a study of the binding mechanisms of the cdk5-p25 and cdk5-CIP complexes. This provides a better understanding of the source of the inhibitory activity of the protein CIP. We use a geometry-based technique to test the hypothesis that p25's truncation increases the flexibility of CIP and thus prevents cdk5 from reaching its active conformation. Our study is based on a geometry-based alignment algorithm, which aligns two given protein conformations with respect to their interfaces. Our results support the flexibility hypothesis and will be used as a basis for targeted molecular dynamics simulations.
C1 [Cardone, Antonio; Sriram, Ram D.] NIST, Gaithersburg, MD 20899 USA.
[Albers, R. Wayne; Pant, Harish C.] NIH, Bethesda, MD 20892 USA.
RP Cardone, A (reprint author), NIST, 100 Bur Dr,Bldg 220,Room A122, Gaithersburg, MD 20899 USA.
EM cardone@nist.gov
NR 58
TC 2
Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD MAY
PY 2010
VL 17
IS 5
BP 707
EP 721
DI 10.1089/cmb.2009.0202
PG 15
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 617HU
UT WOS:000279272400004
PM 20500023
ER
PT J
AU Bratslavsky, G
Kirkali, Z
AF Bratslavsky, Gennady
Kirkali, Ziya
TI The Changing Face of Renal-Cell Carcinoma
SO JOURNAL OF ENDOUROLOGY
LA English
DT Article
ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; RADICAL NEPHRECTOMY; NATURAL-HISTORY;
INTERFERON-ALPHA; SPARING SURGERY; CORTICAL TUMORS; GENETIC-BASIS; CORE
BIOPSY; MASSES; CANCER
AB The present decade can be credited with the improved understanding of renal-cell carcinoma (RCC), its local and systemic management, and various controversies from diagnosis to types of various available interventions. The old paradigms and dogmas are no longer accepted as "the best way" without evidence, and many "old" principles are cautiously questioned. These notions have resulted in new knowledge, questions, arguments, and treatment options. This article will describe the "changing face of RCC" over the past several years and will briefly summarize the major changes and issues in the field of renal oncology. The discussed topics include improved molecular understanding of RCC, management of small renal masses, the safety and accuracy of renal mass biopsy, the emerging role of molecular imaging, the importance of maximal renal preservation, and the evolving role of laparoscopy, robotics, and ablation.
C1 [Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kirkali, Ziya] Dokuz Eylul Univ, Sch Med, Dept Urol, Izmir, Turkey.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr MSC 1107 Bldg 10,CRC,Room 2W-5942, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 70
TC 1
Z9 2
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0892-7790
EI 1557-900X
J9 J ENDOUROL
JI J. Endourol.
PD MAY
PY 2010
VL 24
IS 5
SI SI
BP 753
EP 757
DI 10.1089/end.2009.0520
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 596ZA
UT WOS:000277723400015
PM 20420551
ER
PT J
AU Xu, LQ
Liu, XD
Sun, LG
Yan, H
Liu, Y
Luo, YH
Huang, J
Wang, YH
AF Xu, L. Q.
Liu, X. D.
Sun, L. G.
Yan, H.
Liu, Y.
Luo, Y. H.
Huang, J.
Wang, Y. H.
TI Distribution of radionuclides in the guano sediments of Xisha Islands,
South China Sea and its implication
SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY
LA English
DT Article
DE Xisha Islands; Guano-phosphatic coral sediments; Radioactive nuclides;
(210)Pb dating; (210)Pb flux; (137)Cs
ID HIGH ARCTIC ENVIRONMENT; DONGDAO ISLAND; SOILS
AB Several natural and anthropogenic radionuclides ((210)Pb, (226)Ra and (137)Cs) in guano-phosphatic coral sediments and pure guano particles collected from Ganquan, Guangjin, Jinqing and Jinyin Islands of the Xisha archipelago, South China Sea, were analyzed. The Constant Initial Concentration (CIC) model and the Constant Rate of Supply (CRS) model were applied for age calculation. The average supply rate of (210)Pb was 126 Bq m(-2) a(-1), very close to the flux of northern hemisphere average (125 Bq m(-2) a(-1)). The activities of anthropogenic radionuclides in the sediments were very low, indicating that human nuclear tests did not notably impact this region. The main source of radionuclides in the sediments was from atmospheric precipitation, and the organic matter derived from plant and produced by nutrient-rich guano could further enhance them. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Xu, L. Q.; Liu, X. D.; Sun, L. G.; Yan, H.; Liu, Y.; Luo, Y. H.; Huang, J.] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
[Wang, Y. H.] NIH, Bethesda, MD 20892 USA.
RP Liu, XD (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
EM ycx@ustc.edu.cn; slg@ustc.edu.cn
RI Yan, Hong/I-8970-2014
FU National Basic Research Program of China (973 Program) [2010CB428902];
National Natural Science Foundation of China [40730107, 40876096]; Ph.D.
Programs Foundation of Ministry of Education of China for new teacher
[20093402120004]
FX This work was funded by the National Basic Research Program of China
(973 Program, No. 2010CB428902), National Natural Science Foundation of
China (No. 40730107, 40876096), and Ph.D. Programs Foundation of
Ministry of Education of China for new teacher (20093402120004).
Technician Xia Weilan from Nanjing Institute of Geography and Limnology,
Chinese Academy of Sciences (CAS) helped a lot in radioactivity testing.
Professor Peter Appleby from Liverpool University is acknowledged for
providing valuable information on data analysis. And we would like to
thank all the members for the careful collection of our samples,
including soldiers of PIA. We also thank four anonymous referees for
their constructive comments on the manuscript.
NR 25
TC 21
Z9 21
U1 5
U2 19
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0265-931X
J9 J ENVIRON RADIOACTIV
JI J. Environ. Radioact.
PD MAY
PY 2010
VL 101
IS 5
BP 362
EP 368
DI 10.1016/j.jenvrad.2010.02.004
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 594IP
UT WOS:000277530800006
PM 20346552
ER
PT J
AU Wolff, P
Barbey, AK
Hausknecht, M
AF Wolff, Phillip
Barbey, Aron K.
Hausknecht, Matthew
TI For Want of a Nail: How Absences Cause Events
SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
LA English
DT Article
DE causation; causation by omission; causal models; knowledge structures;
lexical semantics
ID REPRESENTATIONAL MOMENTUM; COUNTERFACTUAL THINKING; MODEL-THEORY;
CAUSATION; CAUSALITY; COVARIATION; DYNAMICS; PHYSICS; FORCE
AB Causation by omission is instantiated when an effect occurs from an absence, as in The absence of nicotine causes withdrawal or Not watering the plant caused it to wilt. The phenomenon has been viewed as an insurmountable problem for process theories of causation, which specify causation in terms of conserved quantities, like force, but not for theories that specify causation in terms of statistical or counterfactual dependencies. A new account of causation challenges these assumptions. According to the force theory, absences are causal when the removal of a force leads to an effect. Evidence in support of this account was found in 3 experiments in which people classified animations of complex causal chains involving force removal, as well as chains involving virtual forces, that is, forces that were anticipated but never realized. In a 4th experiment, the force theory's ability to predict synonymy relationships between different types of causal expressions provided further evidence for this theory over dependency theories. The findings show not only how causation by omission can be grounded in the physical world but also why only certain absences, among the potentially infinite number of absences, are causal.
C1 [Wolff, Phillip; Hausknecht, Matthew] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Barbey, Aron K.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Barbey, Aron K.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD USA.
RP Wolff, P (reprint author), Emory Univ, Dept Psychol, 532 N Kilgo Circle, Atlanta, GA 30322 USA.
EM pwolff@emory.edu
RI Barbey, Aron/L-7312-2015
OI Barbey, Aron/0000-0002-6092-0912
NR 69
TC 20
Z9 20
U1 0
U2 7
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0096-3445
J9 J EXP PSYCHOL GEN
JI J. Exp. Psychol.-Gen.
PD MAY
PY 2010
VL 139
IS 2
BP 191
EP 221
DI 10.1037/a0018129
PG 31
WC Psychology, Experimental
SC Psychology
GA 592IK
UT WOS:000277371900001
PM 20438249
ER
PT J
AU Nemunaitis, G
Maples, PB
Jay, C
Gahl, WA
Huizing, M
Poling, J
Tong, AW
Phadke, AP
Pappen, BO
Bedell, C
Templeton, NS
Kuhn, J
Senzer, N
Nemunaitis, J
AF Nemunaitis, Gregory
Maples, Phillip B.
Jay, Chris
Gahl, William A.
Huizing, Marjan
Poling, Justin
Tong, Alex W.
Phadke, Anagha P.
Pappen, Beena O.
Bedell, Cynthia
Templeton, Nancy S.
Kuhn, Joseph
Senzer, Neil
Nemunaitis, John
TI Hereditary inclusion body myopathy: single patient response to GNE gene
Lipoplex therapy
SO JOURNAL OF GENE MEDICINE
LA English
DT Article
DE gene; GNE; HIBM; Lipoplex; myopathy
ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; DUCHENNES
MUSCULAR-DYSTROPHY; N-ACETYLNEURAMINIC ACID; RIMMED VACUOLES; DISTAL
MYOPATHY; SIALIC ACIDS; IN-VIVO; MUSCLE STRENGTH; SKELETAL-MUSCLE;
CELL-SURFACE
AB Background Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult onset myopathy. It is characterized by mutations of the GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene. Afflicted patients have no therapeutic options. In preclinical testing, we have previously demonstrated the ability to correct GNE gene function and the safety of delivery of wild type GNE gene using a liposomal delivery vehicle.
Methods A single patient (subject #001) with severe HIBM treated by compassionate investigational new drug received four doses of GNE gene Lipoplex via intramuscular injection. GNE transgene expression, downstream induction of sialic acid, safety and muscle function were evaluated.
Results Significant durable improvement in locoregional skeletal muscle function was observed in the injected left extensor carpi radialis longus of #001 in correlation with GNE transgene upregulation and local induction of sialic acid. Other than transient low grade fever and pain at the injection site, no significant toxicity was observed.
Conclusions Proof of principle for manufacturing of 'clinical grade' GNE gene Lipoplex, clinical safety and activity are demonstrated with GNE gene Lipoplex. Further assessment will involve intravenous administration and subsequent phase I trial involving additional but less severely afflicted HIBM patients. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Nemunaitis, Gregory; Bedell, Cynthia; Senzer, Neil; Nemunaitis, John] Mary Crowley Canc Res Ctr, Dallas, TX USA.
[Nemunaitis, Gregory] Metrohlth Med Ctr, Cleveland, OH USA.
[Maples, Phillip B.; Jay, Chris; Tong, Alex W.; Phadke, Anagha P.; Pappen, Beena O.; Templeton, Nancy S.; Senzer, Neil; Nemunaitis, John] Gradalis Inc, Dallas, TX USA.
[Gahl, William A.; Huizing, Marjan; Poling, Justin] NHGRI, NIH, Bethesda, MD 20892 USA.
[Kuhn, Joseph] Gen & Oncol Surg Associates, Dallas, TX USA.
RP Nemunaitis, J (reprint author), 1700 Pacific,Suite 1100, Dallas, TX 75201 USA.
EM jnemunaitis@marycrowley.org
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA
FX The authors would like to acknowledge Susan Mill and Brenda Marr for
their competent and knowledgeable assistance in the preparation of this
manuscript. Samir Sliheet is also acknowledged for transport support. We
thank Dr Gregory Bevels, MD of Primary Care Specialists, LLC
(Alexandria, LA, USA) for his assistance with weekly physical
assessments during the study period. This work was partially supported
by the Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA. John
Nemunaitis and Neil Senzer have direct affiliation with Gradalis, Inc.,
in which they both own common stock. 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.
NR 50
TC 13
Z9 13
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1099-498X
EI 1521-2254
J9 J GENE MED
JI J. Gene. Med.
PD MAY
PY 2010
VL 12
IS 5
BP 403
EP 412
DI 10.1002/jgm.1450
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 601AP
UT WOS:000278030600001
PM 20440751
ER
PT J
AU Frank, D
Gallagher, TH
Sellers, SL
Cooper, LA
Price, EG
Odunlami, AO
Bonham, VL
AF Frank, Danielle
Gallagher, Thomas H.
Sellers, Sherrill L.
Cooper, Lisa A.
Price, Eboni G.
Odunlami, Adebola O.
Bonham, Vence L.
TI Primary Care Physicians' Attitudes Regarding Race-Based Therapies
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT SGIM National Meeting
CY 2007-2008
CL Washington, DC
SP SGIM
DE race-based therapies; race; BiDil; ACE-inhibitors; personalized
medicine; genetics
ID PERSONALIZED MEDICINE; THERAPEUTICS; GENETICS; HEALTH
AB There is little to no information on whether race should be considered in the exam room by those who care for and treat patients. How primary care physicians understand the relationship between genes, race and drugs has the potential to influence both individual care and racial and ethnic health disparities.
To describe physicians' use of race-based therapies, with specific attention to the case of BiDil (isosorbide dinitrate/hydralazine), the first drug approved by the FDA for a race-specific indication, and angiotensin-converting enzyme (ace) inhibitors in their black and white patients.
Qualitative study involving 10 focus groups with 90 general internists.
Black and white general internists recruited from community and academic internal medicine practices participated in the focus groups.Of the participants 64% were less than 45 years of age, and 73% were male.
The focus groups were transcribed verbatim, and the data were analyzed using template analysis.
There was a range of opinions relating to the practice of race-based therapies. Physicians who were supportive of race-based therapies cited several potential benefits including motivating patients to comply with medical therapy and promoting changes in health behaviors by creating the perception that the medication and therapies were tailored specifically for them. Physicians acknowledged that in clinical practice some medications vary in their effectiveness across different racial groups, with some physicians citing the example of ace inhibitors. However, physicians voiced concern that black patients who could benefit from ace inhibitors may not be receiving them. They were also wary that the category of race reflected meaningful differences on a genetic level. In the case of BiDil, physicians were vocal in their concern that commercial interests were the primary impetus behind its creation.
Primary care physicians' opinions regarding race-based therapy reveal a nuanced understanding of race-based therapies and a wariness of their use by physicians.
C1 [Frank, Danielle] VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48105 USA.
[Gallagher, Thomas H.] Univ Washington, Dept Med, Seattle, WA USA.
[Sellers, Sherrill L.] Univ Wisconsin, Sch Social Work, Madison, WI 53706 USA.
[Cooper, Lisa A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Price, Eboni G.] Tulane Univ, Dept Med, New Orleans, LA 70118 USA.
[Odunlami, Adebola O.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bonham, Vence L.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Frank, D (reprint author), VA Ann Arbor Healthcare Syst, 152,Ambulatory Care 11A,2215 Fuller Rd, Ann Arbor, MI 48105 USA.
EM dfp@u.mich.edu
OI Price-Haywood, Eboni/0000-0003-2901-3852
FU Intramural NIH HHS
NR 16
TC 8
Z9 8
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2010
VL 25
IS 5
BP 384
EP 389
DI 10.1007/s11606-009-1190-7
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 584AH
UT WOS:000276721900006
PM 20174973
ER
PT J
AU Bates, CK
Chheda, SG
Dunn, K
Pinsky, L
Karani, R
AF Bates, Carol K.
Chheda, Shobhina G.
Dunn, Kathel
Pinsky, Linda
Karani, Reena
TI Update in Medical Education
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE feedback; evaluation; knowledge assessment; retention; curricula;
Minicard
C1 [Bates, Carol K.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Chheda, Shobhina G.] Univ Wisconsin, Dept Med, Gen Internal Med Sect, Sch Med & Publ Hlth, Madison, WI USA.
[Dunn, Kathel] Natl Lib Med, Bethesda, MD USA.
[Pinsky, Linda] Univ Washington, Sch Med, Seattle, WA USA.
[Karani, Reena] Mt Sinai Sch Med, Brookdale Dept Geriatr, Samuel M Bronfman Dept Med, Dept Med Educ, New York, NY USA.
RP Bates, CK (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Sh 607,330 Brookline Ave, Boston, MA 02215 USA.
EM cbates@bidmc.harvard.edu
OI Dunn, Kathel/0000-0002-6967-130X
NR 3
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2010
VL 25
IS 5
BP 465
EP 469
DI 10.1007/s11606-009-1244-x
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 584AH
UT WOS:000276721900019
PM 20151222
ER
PT J
AU Kim, J
Han, JY
Shaw, B
Mctavish, F
Gustafson, D
AF Kim, Junghyun
Han, Jeong Yeob
Shaw, Bret
Mctavish, Fiona
Gustafson, David
TI The Roles of Social Support and Coping Strategies in Predicting Breast
Cancer Patients' Emotional Well-being Testing Mediation and Moderation
Models
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE breast cancer; coping strategies; emotional well-being; mediator;
moderator; social support
ID RHEUMATOID-ARTHRITIS; PSYCHOLOGICAL DISTRESS; DEPRESSION; PAIN;
RESPONSES; OPTIMISM; STRESS; WOMEN; ADOLESCENTS; ADAPTATION
AB The goal of the current study was to examine how social support and coping strategies are related in predicting emotional well-being of women with breast cancer. In achieving this goal, we examined two hypothesized models: (1) a moderation model where social support and coping strategies interact with each other in affecting psychological well-being; and (2) a mediation model where the level of social support influences choices of coping strategies between self-blame and positive reframing. In general, the data from the current study were more consistent with the mediation model than the moderation model.
C1 [Kim, Junghyun] Kent State Univ, Sch Commun Studies, Kent, OH 44242 USA.
[Han, Jeong Yeob] Univ Georgia, Dept Telecommun, Athens, GA 30602 USA.
[Han, Jeong Yeob; Shaw, Bret] Univ Wisconsin, NCI, Funded Ctr Excellence Canc Commun Res, Madison, WI 53706 USA.
[Shaw, Bret] Univ Wisconsin, Dept Life Sci Commun, Madison, WI 53706 USA.
[Mctavish, Fiona] Univ Wisconsin, CHESS, Madison, WI 53706 USA.
[Gustafson, David] Univ Wisconsin, Coll Engn, Madison, WI 53706 USA.
[Gustafson, David] Univ Wisconsin, NCI, Ctr Excellence Canc Commun, Madison, WI 53706 USA.
RP Kim, J (reprint author), Kent State Univ, Sch Commun Studies, Kent, OH 44242 USA.
EM jkim23@kent.edu
OI Kim, Jung-Hyun/0000-0001-7819-2784
FU NCI NIH HHS [P50 CA095817-05, N02-CO-01040-75, P50 CA095817, P50
CA095817-09, P50 CA095817-07, P50 CA095817-06, P50 CA095817-08]
NR 42
TC 41
Z9 48
U1 3
U2 16
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD MAY
PY 2010
VL 15
IS 4
BP 543
EP 552
DI 10.1177/1359105309355338
PG 10
WC Psychology, Clinical
SC Psychology
GA 594KR
UT WOS:000277537100007
PM 20460411
ER
PT J
AU Bellizzi, KM
Smith, AW
Reeve, BB
Alfano, CM
Bernstein, L
Meeske, K
Baumgartner, KB
Ballard-Barbash, RR
AF Bellizzi, Keith M.
Smith, Ashley Wilder
Reeve, Bryce B.
Alfano, Catherine M.
Bernstein, Leslie
Meeske, Kathy
Baumgartner, Kathy B.
Ballard-Barbash, Rachel R.
TI Posttraumatic Growth and Health-related Quality of Life in a Racially
Diverse Cohort of Breast Cancer Survivors
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE breast cancer; posttraumatic growth; quality of life; race/ethnicity
ID STRESS-DISORDER; SELF-ESTEEM; BENEFIT; WOMEN; DIAGNOSIS; TRAUMA;
PREVALENCE; PREDICTORS; INVENTORY
AB This study examined the relationship between race, religiosity, and posttraumatic growth as well as the association between growth and physical and mental health-related quality of life (HRQOL) in breast cancer survivors (N = 802; M age = 57.2). Multivariate analyses revealed that African American breast cancer survivors reported higher levels of posttraumatic growth than White women. However, this relationship was mediated by religiosity. We found an inverse association with growth and mental HRQOL which might be explained by the fact that growth co-occurs with distress and perhaps women in this sample are still struggling with their disease.
C1 [Bellizzi, Keith M.] Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT 06269 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Duarte, CA 91010 USA.
[Meeske, Kathy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Meeske, Kathy] Childrens Hosp Los Angeles, Hlth Outcomes & Canc Control Res Program, Childrens Ctr Canc & Blood Dis, Los Angeles, CA USA.
[Baumgartner, Kathy B.] Univ Louisville, Fac Affairs, Sch Publ Hlth & Informat Sci, Louisville, KY 40292 USA.
[Ballard-Barbash, Rachel R.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
RP Bellizzi, KM (reprint author), Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT 06269 USA.
EM keith.m.bellizzi@uconn.edu
FU NCI NIH HHS [N01-PC-67010, N01-PC-67007, N01-PC-67009]
NR 45
TC 41
Z9 44
U1 3
U2 10
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD MAY
PY 2010
VL 15
IS 4
BP 615
EP 626
DI 10.1177/1359105309356364
PG 12
WC Psychology, Clinical
SC Psychology
GA 594KR
UT WOS:000277537100014
PM 20460418
ER
PT J
AU Ji, JF
Zhao, L
Budhu, A
Forgues, M
Jia, HL
Qin, LX
Ye, QH
Yu, JM
Shi, XT
Tang, ZY
Wang, XW
AF Ji, Junfang
Zhao, Lei
Budhu, Anuradha
Forgues, Marshonna
Jia, Hu-Liang
Qin, Lun-Xiu
Ye, Qing-Hai
Yu, Jinming
Shi, Xuetao
Tang, Zhao-You
Wang, Xin Wei
TI Let-7g targets collagen type I alpha 2 and inhibits cell migration in
hepatocellular carcinoma
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Hepatocellular carcinoma; MicroRNA; Let-7g; Metastasis; Cell mobility;
Prognosis
ID PANCREATIC-CANCER; MICRORNA FAMILY; SELF-RENEWAL; LUNG-CANCER;
EXPRESSION; METASTASIS; IDENTIFICATION; TRANSFORMATION; GROWTH; EPCAM
AB Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associated with HCC metastasis. Here, we carried out further analyses on one of these microRNAs, let-7g, to determine whether it is functionally linked to HCC metastasis.
Methods: Quantitative real-time polymerase chain reaction was used to determine the level of mature let-7g transcript in HCC clinical specimens and its correlation with patient survival. Ectopic expression of let-7g was carried out in HCC cell lines to assess its influence on cell growth, migration, and invasion.
Results: We confirmed that the level of let-7g was significantly lower in metastatic HCCs compared to metastasis-free HCCs. Moreover, low let-7g expression in a tumour was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of let-7g significantly inhibits HCC cell migration and cell growth. In-silico analysis revealed members of soluble collagens as potential targets of let-7g. Consistently, the levels of type I collagen alpha 2 (COL1A2) and let-7g were inversely correlated in HCC clinical specimens. COL1A2 was experimentally validated as a direct target of let-7g. Moreover, addition of COL1A2 counteracted the inhibitory effect of let-7g on cell migration.
Conclusions: These results suggest that let-7g may suppress HCC metastasis partially through targeting COL1A2. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Ji, Junfang; Zhao, Lei; Budhu, Anuradha; Forgues, Marshonna; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jia, Hu-Liang; Qin, Lun-Xiu; Ye, Qing-Hai; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
[Jia, Hu-Liang; Qin, Lun-Xiu; Ye, Qing-Hai; Tang, Zhao-You] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Zhao, Lei; Yu, Jinming; Shi, Xuetao] Shandong Prov Tumour Hosp & Inst Oncol, Jinan, Peoples R China.
RP Wang, XW (reprint author), 37 Convent Dr,MSC 4258,Bldg 37,Room 3044A, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Centre for Cancer Research; National Cancer Institute [Z01 BC 010313,
Z01 BC 010876]; China National Natural Scientific Fund [30801383]
FX The authors who have taken part in this study declared that they do not
have anything to declare regarding funding from industry or conflict of
interest with respect to this manuscript. We thank the NIH Fellows
Editorial Board for editing the manuscript. This work was supported by
the Intramural Research Program of the Centre for Cancer Research, the
National Cancer Institute (Z01 BC 010313 and Z01 BC 010876). L.Z. was
also supported by China National Natural Scientific Fund (30801383).
NR 37
TC 101
Z9 109
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAY
PY 2010
VL 52
IS 5
BP 690
EP 697
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 606HS
UT WOS:000278414200014
PM 20338660
ER
PT J
AU Macey, MR
Sturgill, JL
Morales, JK
Falanga, YT
Morales, J
Norton, SK
Yerram, N
Shim, H
Fernando, J
Gifillan, AM
Gomez, G
Schwartz, L
Oskeritzian, C
Spiegel, S
Conrad, D
Ryan, JJ
AF Macey, Matthew R.
Sturgill, Jamie L.
Morales, Johanna K.
Falanga, Yves T.
Morales, Joshua
Norton, Sarah K.
Yerram, Nitin
Shim, Hoon
Fernando, Josephine
Gifillan, Alasdair M.
Gomez, Gregorio
Schwartz, Lawrence
Oskeritzian, Carole
Spiegel, Sarah
Conrad, Daniel
Ryan, John J.
TI IL-4 and TGF-beta 1 Counterbalance One Another while Regulating Mast
Cell Homeostasis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; FC-EPSILON-RI; IGE RECEPTOR EXPRESSION;
NECROSIS-FACTOR-ALPHA; T-CELLS; IN-VITRO; MEDIATOR RELEASE; ALLERGIC
DISEASE; KIT EXPRESSION; STAT6 ISOFORM
AB Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-beta 1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-beta 1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-beta 1 had balancing effects on mast cell survival, migration, and Fc epsilon RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-beta 1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-beta 1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy. The Journal of Immunology, 2010, 184: 4688-4695.
C1 [Macey, Matthew R.; Morales, Johanna K.; Falanga, Yves T.; Morales, Joshua; Yerram, Nitin; Shim, Hoon; Fernando, Josephine; Ryan, John J.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
[Macey, Matthew R.; Sturgill, Jamie L.; Morales, Johanna K.; Falanga, Yves T.; Norton, Sarah K.; Yerram, Nitin; Shim, Hoon; Fernando, Josephine; Gomez, Gregorio; Schwartz, Lawrence; Oskeritzian, Carole; Spiegel, Sarah; Conrad, Daniel; Ryan, John J.] Virginia Commonwealth Univ, Allergy & Allerg Dis Cooperat Res Ctr, Richmond, VA 23284 USA.
[Sturgill, Jamie L.; Norton, Sarah K.; Gomez, Gregorio; Schwartz, Lawrence; Oskeritzian, Carole; Spiegel, Sarah; Conrad, Daniel] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA.
[Gifillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Ryan, JJ (reprint author), Virginia Commonwealth Univ, Dept Biol, Box 842012, Richmond, VA 23284 USA.
EM jjryan@vcu.edu
FU National Institutes of Health [1R01AI59638, U19AI077435, R01AI50094,
K01AR053186]; Jeffress Trust Foundation [J-833]
FX This work was supported by grants from the National Institutes of Health
(1R01AI59638 to J.J.R.; U19AI077435 to J.J.R., L.S., S.S., and D.C.:
R01AI50094 to S.S.; and K01AR053186 to C.O.), The Jeffress Trust
Foundation (J-833 to J.J.R.), and the National Institutes of Health
intramural program (to A.M.G.).
NR 62
TC 15
Z9 15
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2010
VL 184
IS 9
BP 4688
EP 4695
DI 10.4049/jimmunol.0903477
PG 8
WC Immunology
SC Immunology
GA 588SD
UT WOS:000277093000019
PM 20304823
ER
PT J
AU Maenetje, P
Riou, C
Casazza, JP
Ambrozak, D
Hill, B
Gray, G
Koup, RA
de Bruyn, G
Gray, CM
AF Maenetje, Pholo
Riou, Catherine
Casazza, Joseph P.
Ambrozak, David
Hill, Brenna
Gray, Glenda
Koup, Richard A.
de Bruyn, Guy
Gray, Clive M.
TI A Steady State of CD4(+) T Cell Memory Maturation and Activation Is
Established during Primary Subtype C HIV-1 Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNE ACTIVATION; ANTIGEN LOAD; VIRAL LOAD; SET-POINT; IN-VIVO; VIRUS;
RESPONSES; DEPLETION; VIREMIA; AIDS
AB The functional integrity of CD4(+) T cells is crucial for well-orchestrated immunity and control of HIV-1 infection, but their selective depletion during infection creates a paradox for understanding a protective response. We used multiparameter flow cytometry to measure activation, memory maturation, and multiple functions of total and Ag-specific CD4(+) T cells in 14 HIV-1 and CMV-coinfected individuals at 3 and 12 mo post HIV-1 infection. Primary HIV-1 infection was characterized by elevated levels of CD38, HLA-DR, and Ki67 in total memory and Gag-specific CD4(+) and CD8(+) T cells. In both HIV-infected and 15 uninfected controls, the frequency of activated cells was uniformly distributed among early differentiated (ED; CD45RO(+)CD27(+)), late differentiated (CD45RO(+)CD27(-)), and fully differentiated effector (CD45RO(-)CD27(-)) memory CD4(+) T cells. In HIV-1 infected individuals, activated CD4(+) T cells significantly correlated with viremia at 3 mo postinfection (r = 0.79, p = 0.0007) and also harbored more gag provirus DNA copies than nonactivated cells (p = 0.04). Moreover, Gag-specific ED CD4(+) T cells inversely associated with plasma viral load (r = -0.87, p < 0.0001). Overall, we show that low copy numbers of gag provirus and plasma RNA copies associated with low CD4 activation as well as accumulation of ED HIV-specific CD4(+) memory. Significant positive correlations between 3 and 12 mo activation and memory events highlighted that a steady state of CD4(+) T cell activation and memory maturation was established during primary infection and that these cells were unlikely to be involved in influencing the course of viremia in the first 12 mo of HIV-1 infection. The Journal of Immunology, 2010, 184: 4926-4935.
C1 [Maenetje, Pholo; Riou, Catherine; Gray, Clive M.] Natl Inst Communicable Dis, AIDS Res Unit, ZA-2131 Johannesburg, South Africa.
[Gray, Glenda; de Bruyn, Guy] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Casazza, Joseph P.; Ambrozak, David; Hill, Brenna; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Gray, CM (reprint author), Natl Inst Communicable Dis, AIDS Res Unit, Private Bag X4, ZA-2131 Johannesburg, South Africa.
EM cgray@nicd.ac.za
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; U.S. Department of Health and Human Services
[AI070079]; South African AIDS Vaccine Initiative; Columbia
University-Southern Africa Fogarty AIDS International; Canadian African
Prevention Trials network
FX This work was supported in part by the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, U.S. Department of
Health and Human Services Grant AI070079 (to G.d.B.), and a South
African AIDS Vaccine Initiative grant (to C.M.G.). P.M. was supported by
a Columbia University-Southern Africa Fogarty AIDS International
Training Fellowship and C.R. was supported by the Canadian African
Prevention Trials network.
NR 51
TC 16
Z9 16
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2010
VL 184
IS 9
BP 4926
EP 4935
DI 10.4049/jimmunol.0903771
PG 10
WC Immunology
SC Immunology
GA 588SD
UT WOS:000277093000044
PM 20363974
ER
PT J
AU Avarez-Errico, D
Yamashita, Y
Suzuki, R
Odom, S
Furumoto, Y
Yamashita, T
Rivera, J
AF Avarez-Errico, Damiana
Yamashita, Yumi
Suzuki, Ryo
Odom, Sandra
Furumoto, Yasuko
Yamashita, Toshiyuki
Rivera, Juan
TI Functional Analysis of Lyn Kinase A and B Isoforms Reveals Redundant and
Distinct Roles in Fc epsilon RI-Dependent Mast Cell Activation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROTEIN-TYROSINE KINASE; HIGH-AFFINITY RECEPTOR; SRC FAMILY KINASES;
CYTOKINE PRODUCTION; IMMUNOGLOBULIN-E; INOSITOL 5'-PHOSPHATASE;
HEMATOPOIETIC-CELLS; ALLERGIC RESPONSES; CUTTING EDGE; IGE RECEPTOR
AB Engagement of Fc epsilon RI causes its phosphorylation by Lyn kinase. Two alternatively spliced variants, Lyn A and B, are expressed in mast cells, and both isoforms interact with Fc epsilon RI. Unlike Lyn A, Lyn B lacks a 21-aa region in the N-terminal unique domain. In this study, we investigated the role of Lyn A and B isoforms in mast cell signaling and responses. Lyn B was found to be a poor inducer of mast cell degranulation and was less potent in both inositol 1,4,5-triphosphate production and calcium responses. Expression of Lyn B alone showed reduced phosphorylation of both phospholipase C gamma-1 and -2 and decreased interaction of phospholipase C gamma-1 with the phosphorylated linker for activation of T cells. Lyn B also showed increased binding of tyrosine-phosphorylated proteins, which included the negative regulatory lipid phosphatase SHIP-1. In contrast, both Lyn A and B caused similar total cellular tyrosine phosphorylation and Fc epsilon RI phosphorylation and neither Lyn A nor Lyn B alone could completely restore mast cell degranulation or dampen the excessive cytokine production seen in the absence of Lyn. However, expression of both isoforms showed complementation and normalized responses. These findings demonstrate that Lyn B differs from Lyn A in its association with SHIP-1 and in the regulation of calcium responses. However, complementation of both isoforms is required in mast cell activation. The Journal of Immunology, 2010, 184: 5000-5008.
C1 [Avarez-Errico, Damiana; Yamashita, Yumi; Suzuki, Ryo; Odom, Sandra; Furumoto, Yasuko; Yamashita, Toshiyuki; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Yamashita, Yumi; Yamashita, Toshiyuki] Ohu Univ, Sch Pharmaceut Sci, Dept Immunol, Fukushima, Japan.
RP Rivera, J (reprint author), NIAMSD, Immunogenet Mol Lab, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM juan_rivera@nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX This work was supported by the intramural program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases of the
National Institutes of Health.
NR 44
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2010
VL 184
IS 9
BP 5000
EP 5008
DI 10.4049/jimmunol.0904064
PG 9
WC Immunology
SC Immunology
GA 588SD
UT WOS:000277093000052
ER
PT J
AU Metenou, S
Dembele, B
Konate, S
Dolo, H
Coulibaly, SY
Coulibaly, YI
Diallo, AA
Soumaoro, L
Coulibaly, ME
Sanogo, D
Doumbia, SS
Traore, SF
Mahanty, S
Klion, A
Nutman, TB
AF Metenou, Simon
Dembele, Benoit
Konate, Siaka
Dolo, Housseini
Coulibaly, Siaka Y.
Coulibaly, Yaya I.
Diallo, Abdallah A.
Soumaoro, Lamine
Coulibaly, Michel E.
Sanogo, Dramane
Doumbia, Salif S.
Traore, Sekou F.
Mahanty, Siddhartha
Klion, Amy
Nutman, Thomas B.
TI At Homeostasis Filarial Infections Have Expanded Adaptive T Regulatory
but Not Classical Th2 Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN SCHISTOSOMIASIS-MANSONI; HUMAN LYMPHATIC FILARIASIS; HUMAN
HELMINTH INFECTION; PAHANGI 3RD-STAGE LARVAE; WUCHERERIA-BANCROFTI;
PARASITE INFECTIONS; IMMUNE REGULATION; IFN-GAMMA; RESPONSES; ANTIGEN
AB Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fir, as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fir compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10 producing aTreg/Tr1s in Fir. Together, these data show that at steady state, IL-10 producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level. The Journal of Immunology, 2010, 184: 5375-5382.
C1 [Metenou, Simon; Mahanty, Siddhartha; Klion, Amy; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Siaka Y.; Coulibaly, Yaya I.; Diallo, Abdallah A.; Soumaoro, Lamine; Coulibaly, Michel E.; Sanogo, Dramane; Doumbia, Salif S.; Traore, Sekou F.] Univ Bamako, Fac Med Pharm & Dent, Filariasis Unit, Bamako, Mali.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room B1-03, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
RI Metenou, Simon/C-1101-2013;
OI Klion, Amy/0000-0002-4986-5326; Mahanty, Siddhartha/0000-0003-1068-0524
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 54
TC 51
Z9 51
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2010
VL 184
IS 9
BP 5375
EP 5382
DI 10.4049/jimmunol.0904067
PG 8
WC Immunology
SC Immunology
GA 588SD
UT WOS:000277093000093
PM 20357251
ER
PT J
AU Demaria, S
Pikarsky, E
Karin, M
Coussens, LM
Chen, YC
El-Omar, EM
Trinchieri, G
Dubinett, SM
Mao, JT
Szabo, E
Krieg, A
Weiner, GJ
Fox, BA
Coukos, G
Wang, E
Abraham, RT
Carbone, M
Lotze, MT
AF Demaria, Sandra
Pikarsky, Eli
Karin, Michael
Coussens, Lisa M.
Chen, Yen-Ching
El-Omar, Emad M.
Trinchieri, Giorgio
Dubinett, Steven M.
Mao, Jenny T.
Szabo, Eva
Krieg, Arthur
Weiner, George J.
Fox, Bernard A.
Coukos, George
Wang, Ena
Abraham, Robert T.
Carbone, Michele
Lotze, Michael T.
TI Cancer and Inflammation: Promise for Biologic Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Review
DE chronic inflammation; damage-associated molecular pattern molecules
(DAMPs); pathogen-associated molecular pattern molecules (PAMPs);
cytokine polymorphisms; COX2; ethyl pyruvate; steroids; HMGB1; TGF beta;
innate immunity
ID MOLECULAR-PATTERN MOLECULES; MOBILITY GROUP BOX-1; FAMILIAL ADENOMATOUS
POLYPOSIS; SQUAMOUS-CELL CARCINOMA; REGULATORY T-CELLS; HEPATIC
ISCHEMIA/REPERFUSION INJURY; HELICOBACTER-PYLORI INFECTION;
ISCHEMIA-REPERFUSION INJURY; PREVENT COLORECTAL ADENOMAS; POSITIVE
DENDRITIC CELLS
AB Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer and limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis and also the nature and quality of the immune infiltrate. Both environmental and genetic factors enhance the risk of cigarette smoking, Helicobacter pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models that incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogens and damage-associated molecular pattern molecules are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPAR gamma, ethyl pyruvate and steroids, and several novel agents on the horizon.
C1 [Lotze, Michael T.] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA 15213 USA.
[Demaria, Sandra] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Pikarsky, Eli] Hadassah Hebrew Univ, Med Ctr, Dept Pathol, Jerusalem, Israel.
[Karin, Michael] Univ Calif San Diego, Med Ctr, Sch Med, San Diego, CA 92103 USA.
[Karin, Michael] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA.
[Coussens, Lisa M.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA.
[Coussens, Lisa M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Chen, Yen-Ching] Natl Taiwan Univ, Inst Prevent Med, Taipei 10764, Taiwan.
[Chen, Yen-Ching] Natl Taiwan Univ, Res Ctr Gene Environm & Human Hlth, Taipei 10764, Taiwan.
[El-Omar, Emad M.] Univ Aberdeen, Inst Med Sci, Div Appl Med, Aberdeen, Scotland.
[Trinchieri, Giorgio] NCI, Frederick, MD 21701 USA.
[Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA.
[Dubinett, Steven M.] Univ Calif Los Angeles, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA.
[Mao, Jenny T.] New Mexico VA Healthcare Syst, Pulm & Crit Care Sect, Albuquerque, NM USA.
[Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Krieg, Arthur] Pfizer, Cambridge, MA USA.
[Weiner, George J.] Univ Iowa, Iowa City, IA USA.
[Fox, Bernard A.] Earle A Charles Res Inst, Portland, OR USA.
[Coukos, George] Abramson Canc Ctr, Philadelphia, PA USA.
[Wang, Ena] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Abraham, Robert T.] Wyeth Res, Pearl River, NY USA.
[Carbone, Michele] Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
RP Lotze, MT (reprint author), Univ Pittsburgh, Inst Canc, Dept Surg, 5117 Ctr Ave,Suite G-27A, Pittsburgh, PA 15213 USA.
EM lotzemt@upmc.edu
RI Chen, Yen-Ching/D-1098-2010;
OI Chen, Yen-Ching/0000-0002-8159-7202; Demaria, Sandra/0000-0003-4426-0499
FU NIH [1 P01 CA 101944-04]; Pfizer
FX This project was funded in part by a grant from the NIH 1 P01 CA
101944-04 (Michael T. Lotze) Integrating NK and DC into Cancer Therapy
National Cancer Institute. We thank the iSBTc leadership, management,
and in particular Roseann Marotz (iSBTc) for her steadfast support of
this project.; R. T. A. is an employee and shareholder of Pfizer
Pharmaceuticals. S. M. D. is a member of the Scientific Advisory Board
for Tragara Pharmaceuticals. B. A. F. serves as a Consultant/Advisory
Board receiving consulting fee from Micromet; on the Board of
Directors/Scientific Advisory Board receiving stock/fee for NeoPharm;
serves as a Consultant/Advisory Board receiving consulting fee for
Novartis; serves as a consultant receiving fee from Pfizer; serves as a
consultant receiving research grant from Sangamo; is Co-Founder
receiving Ownership Interest of UBiVAC LLC. A. M. K. is an employee of
Pfizer Inc., owns stock in Pfizer, and is an inventor on patents
relating to the subject matter of the article. G.J.W. serves on a
Scientific Advisory Board for Genentech.
NR 140
TC 131
Z9 136
U1 4
U2 30
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2010
VL 33
IS 4
BP 335
EP 351
DI 10.1097/CJI.0b013e3181d32e74
PG 17
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 590IG
UT WOS:000277218200001
PM 20386472
ER
PT J
AU Correale, P
Rotundo, MS
Del Vecchio, MT
Remondo, C
Migali, C
Ginanneschi, C
Tsang, KY
Licchetta, A
Mannucci, S
Loiacono, L
Tassone, P
Francini, G
Tagliaferri, P
AF Correale, Pierpaolo
Rotundo, Maria Saveria
Del Vecchio, Maria Teresa
Remondo, Cinzia
Migali, Cristina
Ginanneschi, Chiara
Tsang, Kwong Y.
Licchetta, Antonella
Mannucci, Susanna
Loiacono, Lucia
Tassone, Pierfrancesco
Francini, Guido
Tagliaferri, Pierosandro
TI Regulatory (FoxP3(+)) T-cell Tumor Infiltration Is a Favorable
Prognostic Factor in Advanced Colon Cancer Patients Undergoing Chemo or
Chemoimmunotherapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE chemotherapy; immunotherapy; colon cancer; FoxP3(+) T-cell;
immunoregulatory T cells
ID STIMULATING FACTOR; COLORECTAL-CARCINOMA; IMMUNE-RESPONSE;
BREAST-CANCER; MELANOMA; GEMCITABINE; EXPRESSION; ANTIGEN;
CYCLOPHOSPHAMIDE; AUTOIMMUNITY
AB Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies, like GOLFIG chemoimmunotherapy (gemcitabine, oxaliplatin, 5-fluorouracil/folinic acid, granulocyte macrophage colony-stimulating factor, and aldesleukine), that resulted a safe and very active regimen. Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs, increase of central memory T cells, and decrease of regulatory T cells (T-reg) in the peripheral blood. We thus investigated a potential correlation between the T-reg tumor infiltration at diagnosis and the clinical outcome in a current randomized phase 3 trial aimed to compare the GOLFIG regimen with the standard FOLFOX chemotherapy (GOLFIG-2). An immunohistochemistry study was carried out to quantify the infiltration of T-reg/FoxP3(+) T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. T-reg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progression-free survival (PFS). Higher T-reg tumor infiltration scores were associated with a better prognosis in the whole series (T-reg high score vs. low score: overall survival = mean 43.2 mo vs. 28.6 mo, P = 0.0005) and a better outcome after treatment (T-reg high score vs. low score: PFS = mean 15.8 mo vs. 8.8 mo, P = 0.0009; treatment-relative survival = mean 23.1 mo vs. 18.2 mo, P = 0.004). PFS was significantly longer in GOLFIG high versus all other subgroups (mean 18.1 mo vs. 9.9 mo, P = 0.01). Our results suggest that a higher FoxP3(+) T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy.
C1 [Rotundo, Maria Saveria; Tassone, Pierfrancesco; Tagliaferri, Pierosandro] Magna Graecia Univ Catanzaro, Med Oncol Unit, Catanzaro, Italy.
[Rotundo, Maria Saveria; Tassone, Pierfrancesco; Tagliaferri, Pierosandro] Magna Graecia Univ Catanzaro, Referral Ctr Innovat Treatments, Catanzaro, Italy.
[Rotundo, Maria Saveria; Tassone, Pierfrancesco; Tagliaferri, Pierosandro] Tommaso Campanella Canc Ctr, Catanzaro, Italy.
[Correale, Pierpaolo; Remondo, Cinzia; Migali, Cristina; Licchetta, Antonella; Loiacono, Lucia; Francini, Guido] Univ Siena, Sch Med, Dept Giorgio Segre Pharmacol, Sect Med Oncol, Catanzaro, Italy.
[Del Vecchio, Maria Teresa; Ginanneschi, Chiara; Mannucci, Susanna] Univ Siena, Sch Med, Dept Oncol, Pathol Sect, Catanzaro, Italy.
[Tsang, Kwong Y.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Tagliaferri, P (reprint author), Magna Graecia Univ Catanzaro, Med Oncol Unit, Campus Salvatore Venuta, Catanzaro, Italy.
EM tagliaferri@unicz.it
RI Correale, Pierpaolo/K-1640-2016
OI Correale, Pierpaolo/0000-0003-2154-6734
NR 32
TC 98
Z9 103
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2010
VL 33
IS 4
BP 435
EP 441
DI 10.1097/CJI.0b013e3181d32f01
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 590IG
UT WOS:000277218200010
PM 20386463
ER
PT J
AU Mosbruger, TL
Duggal, P
Goedert, JJ
Kirk, GD
Hoots, WK
Tobler, LH
Busch, M
Peters, MG
Rosen, HR
Thomas, DL
Thio, CL
AF Mosbruger, Timothy L.
Duggal, Priya
Goedert, James J.
Kirk, Gregory D.
Hoots, W. Keith
Tobler, Leslie H.
Busch, Michael
Peters, Marion G.
Rosen, Hugo R.
Thomas, David L.
Thio, Chloe L.
TI Large-Scale Candidate Gene Analysis of Spontaneous Clearance of
Hepatitis C Virus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID MULTICENTER AIDS COHORT; VIRAL CLEARANCE; INFECTION; RECEPTOR;
INTERLEUKIN-18; POLYMORPHISMS; ASSOCIATION; PROTEIN; HEMOPHILIA;
MODULATION
AB Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. We determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.05) and Haploview (version 4.1) software packages were used to perform association, permutation, and haplotype analyses stratified by African American and European American race. Of the 1536 SNPs tested, 1426 (92.8%) were successfully genotyped. In African Americans, we identified 18 SNPs located in 11 gene regions that were associated with HCV infection outcome (empirical P value, < .01). In European Americans, there were 20 SNPs located in 8 gene regions associated with HCV infection outcome. Four of the gene regions studied (TNFSF18, TANK, HAVCR1, and IL18BP) contained SNPs for which the empirical P value was <.01 in both of the race groups. In this large-scale analysis of 1426 genotyped SNPs in 112 candidate genes, we identified 4 gene regions that are likely candidates for a role in HCV clearance or persistence in both African Americans and European Americans.
C1 [Mosbruger, Timothy L.; Duggal, Priya; Kirk, Gregory D.; Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Baltimore, MD USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hoots, W. Keith] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Tobler, Leslie H.; Busch, Michael] Blood Syst Res Inst, San Francisco, CA USA.
[Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Rosen, Hugo R.] Univ Colorado, Denver, CO 80202 USA.
RP Thio, CL (reprint author), 855 N Wolfe St,Rm 533, Baltimore, MD 21205 USA.
EM cthio@jhmi.edu
FU National Institutes of Health (NIH) [R01-DA13324, R01-HL076902,
R01-HD41224, R01-DA0334, R01-DA12568, UO1-HD-32632, U01-AI-35004,
U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, U01-AI-42590];
National Cancer Institute [N02-CP-91027]
FX National Institutes of Health (NIH; grants R01-DA13324, R01-HL076902,
R01-HD41224, R01-DA0334, R01-DA12568, UO1-HD- 32632, U01-AI-35004,
U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and
U01-AI-42590); National Cancer Institute (contract N02-CP-91027 with RTI
International). The study was also funded in part by the Intramural
Research Program, NIH.
NR 35
TC 36
Z9 36
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2010
VL 201
IS 9
BP 1371
EP 1380
DI 10.1086/651606
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 577UB
UT WOS:000276248400014
PM 20331378
ER
PT J
AU Bukh, J
Meuleman, P
Tellier, R
Engle, RE
Feinstone, SM
Eder, G
Satterfield, WC
Govindarajan, S
Krawczynski, K
Miller, RH
Leroux-Roels, G
Purcell, RH
AF Bukh, Jens
Meuleman, Philip
Tellier, Raymond
Engle, Ronald E.
Feinstone, Stephen M.
Eder, Gerald
Satterfield, William C.
Govindarajan, Sugantha
Krawczynski, Krzysztof
Miller, Roger H.
Leroux-Roels, Geert
Purcell, Robert H.
TI Challenge Pools of Hepatitis C Virus Genotypes 1-6 Prototype Strains:
Replication Fitness and Pathogenicity in Chimpanzees and Human
Liver-Chimeric Mouse Models
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CELL-CULTURE-SYSTEMS; INFECTIOUS IN-VIVO; 6 MAJOR GENOTYPES; UPA-SCID
MOUSE; INOCULATED CHIMPANZEES; FULMINANT-HEPATITIS; NUCLEOTIDE-SEQUENCE;
MOLECULAR CLONE; CDNA-CLONE; TRANSCRIPTS
AB Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo.
C1 [Bukh, Jens; Tellier, Raymond; Engle, Ronald E.; Miller, Roger H.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Feinstone, Stephen M.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Satterfield, William C.] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Michale E Keeling Ctr Comparat Med & Res, Bastrop, TX USA.
[Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA.
[Krawczynski, Krzysztof] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA.
[Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, Hvidovre, Denmark.
[Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark.
[Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, Copenhagen, Denmark.
[Eder, Gerald] Karl Landsteiner Inst Epidemiol Infect Disorders, St Polten, Austria.
[Meuleman, Philip; Leroux-Roels, Geert] Ghent Univ & Hosp, Ctr Vaccinol, Ghent, Belgium.
RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 50,50 S Dr MSC 8009, Bethesda, MD 20892 USA.
EM jbukh@niaid.nih.gov
RI Meuleman, Philip/H-2899-2013
OI Meuleman, Philip/0000-0001-6821-234X
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [N01-A0-2713]; University of Copenhagen; Lundbeck
Foundation; Ghent University [01G00507]; Belgian State via the
Interuniversity Attraction Poles Program [P6/36 HEPRO]; European Union;
Research Foundation Flanders (FWO-Vlaanderen)
FX Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (contract
N01-A0-2713); University of Copenhagen (professorship to J.B.); Lundbeck
Foundation (external funding to J.B.); Ghent University (Concerted
Action Grant 01G00507); the Belgian State via the Interuniversity
Attraction Poles Program (grant P6/36 HEPRO); European Union (6th
Framework-HEPACIVAC); The Research Foundation Flanders (FWO-Vlaanderen;
postdoctoral fellowship to P.M.).
NR 50
TC 43
Z9 43
U1 0
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2010
VL 201
IS 9
BP 1381
EP 1389
DI 10.1086/651579
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 577UB
UT WOS:000276248400015
PM 20353362
ER
PT J
AU Memoli, MJ
Hrabal, RJ
Hassantoufighi, A
Jagger, BW
Sheng, ZM
Eichelberger, MC
Taubenberger, JK
AF Memoli, Matthew J.
Hrabal, Rachel J.
Hassantoufighi, Arash
Jagger, Brett W.
Sheng, Zong-Mei
Eichelberger, Maryna C.
Taubenberger, Jeffery K.
TI Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2
Virus in an Immunocompromised Host
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID A H3N2 VIRUSES; OSELTAMIVIR-RESISTANT; SEASONAL INFLUENZA; ISOLATED
WORLDWIDE; H1N1; INFECTION; SURVEILLANCE; MORTALITY; ZANAMIVIR; OUTBREAK
AB Background. The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.
Methods. Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture.
Results. An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed.
Conclusions. An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised.
C1 [Memoli, Matthew J.; Hrabal, Rachel J.; Jagger, Brett W.; Sheng, Zong-Mei; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hassantoufighi, Arash; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Memoli, MJ (reprint author), NIAID, Resp Virus Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, MSC 3203 33 N Dr, Bethesda, MD 20892 USA.
EM memolim@niaid.nih.gov
OI Hagey, Rachel/0000-0002-4368-3169
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Food and Drug Administration
FX Intramural program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health, and the Food and Drug
Administration.
NR 38
TC 23
Z9 25
U1 1
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2010
VL 201
IS 9
BP 1397
EP 1403
DI 10.1086/651610
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 577UB
UT WOS:000276248400017
PM 20350163
ER
PT J
AU He, XS
Nanda, S
Ji, XH
Calderon-Rodriguez, GM
Greenberg, HB
Liang, TJ
AF He, Xiao-Song
Nanda, Santosh
Ji, Xuhuai
Calderon-Rodriguez, Gloria M.
Greenberg, Harry B.
Liang, T. Jake
TI Differential Transcriptional Responses to Interferon-alpha and
Interferon-gamma in Primary Human Hepatocytes
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID HEPATITIS-C-VIRUS; PEGINTERFERON ALPHA-2A; SIGNAL-TRANSDUCTION;
ANTIVIRAL THERAPY; RNA REPLICATION; GENE-EXPRESSION; PLUS RIBAVIRIN;
INDUCTION; SUPPRESSOR; CYTOKINE-SIGNALING-3
AB Interferon (IFN) plays a central role in the innate and adaptive antiviral immune responses. While IFN-alpha is currently approved for treating chronic hepatitis B and hepatitis C, in limited studies, IFN-gamma has not been shown to be effective for chronic hepatitis B or C. To identify the potential mechanism underlying the differential antiviral effects of IFN-alpha and IFN-gamma, we used cDNA microarray to profile the global transcriptional response to IFN-alpha and IFN-gamma in primary human hepatocytes, the target cell population of hepatitis viruses. Our results reveal distinct patterns of gene expression induced by these 2 cytokines. Overall, IFN-alpha induces more genes than IFN-gamma at the transcriptional level. Distinct sets of genes were induced by IFN-alpha and IFN-gamma with limited overlaps. IFN-alpha induces gene transcription at an early time point (6 h) but not at a later time point (18 h), while the effects of IFN-gamma are more prominent at 18 h than at 6 h, suggesting a delayed transcriptional response to IFN-gamma in the hepatocytes. These findings indicate differential actions of IFN-alpha and IFN-gamma in the context of therapeutic intervention for chronic viral infections in the liver.
C1 [He, Xiao-Song; Ji, Xuhuai; Greenberg, Harry B.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[He, Xiao-Song; Ji, Xuhuai; Greenberg, Harry B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Nanda, Santosh; Calderon-Rodriguez, Gloria M.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
RP He, XS (reprint author), VA Med Ctr 154C, 3801 Miranda Ave, Palo Alto, CA 94304 USA.
EM xiaosong@stanford.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH;
NIH [U19 AI40034, P30 DK56339]; REAP Center, Department of Veterans
Affairs
FX We would like to thank Stephen Strom and his colleagues at the
University of Pittsburgh for providing the primary human hepatocytes
through the Liver Tissue Procurement and Distribution System
(N01-DK-7-0004/HHSN26700700004C). This work was supported in part by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH, the NIH grants U19 AI40034 and P30
DK56339, and a REAP Center grant from the Department of Veterans
Affairs.
NR 40
TC 12
Z9 14
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD MAY
PY 2010
VL 30
IS 5
BP 311
EP 320
DI 10.1089/jir.2009.0082
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 596ZC
UT WOS:000277723600005
PM 20038212
ER
PT J
AU Huter, EN
Natarajan, K
Torgerson, TR
Glass, DD
Shevach, EM
AF Huter, Eva N.
Natarajan, Kannan
Torgerson, Troy R.
Glass, Deborah D.
Shevach, Ethan M.
TI Autoantibodies in Scurfy Mice and IPEX Patients Recognize Keratin 14
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; LYMPHORETICULAR DISEASE; IMMUNE DYSREGULATION;
MOUSE; ENTEROPATHY; FOXP3; POLYENDOCRINOPATHY; DIFFERENTIATION;
KERATINOCYTES; AUTOIMMUNITY
AB Scurfy mice have a deletion in the Foxp3 gene, resulting in a failure to generate Foxp3(+) regulatory T cells, and they subsequently develop severe CD4(+) T-cell-mediated autoimmune inflammation. Multiple organs are involved, but the skin is one of the main organs affected. During the course of disease, Scurfy mice develop autoantibodies; however, the targeted antigens are unknown. In this study, we show that Scurfy mice develop autoantibodies directed against skin antigens. Using western blot analysis, we found that Scurfy serum reacted with proteins in total skin lysate, as well as in a keratinocyte lysate. Most of the Scurfy sera tested identified a major band at 50 kDa. Transfer of Scurfy CD4(+) T cells into nu/nu mice yielded autoantibodies with similar reactivity. Further analysis using 2D western blots, followed by peptide mass fingerprinting, identified several keratins as targets. To confirm this observation, we chose one of the identified targets, keratin 14, and prepared recombinant proteins encompassing the N-terminal, middle, and C-terminal portions of the keratin 14 protein. Scurfy serum predominantly recognized the C-terminal fragment. Sera from patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, the human disease resulting from FOXP3 mutations, also recognized skin antigens, including keratin 14. Thus, the results of our study indicate that autoantibodies in Scurfy mice and patients with IPEX target keratins.
C1 [Huter, Eva N.; Natarajan, Kannan; Glass, Deborah D.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Torgerson, Troy R.] Univ Washington, Dept Pediat, Ctr Immun & Immunotherapies, Seattle, WA 98195 USA.
[Torgerson, Troy R.] Seattle Childrens Res Inst, Seattle, WA USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases
FX We thank Dr U. Lichti, Dr J. Anders, Dr S. Yuspa, and Dr M. C. Udey for
helpful discussions. We also thank Dr C. Hammer, Dr M. A. Robinson, Dr
M. Zhao, and Dr R. Martin (Mass Spectrometry Laboratory, Protein
Biochemistry Section at the National Institute of Allergy and Infectious
Diseases) for the help with protein identification. This work was
supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases.
NR 27
TC 12
Z9 13
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2010
VL 130
IS 5
BP 1391
EP 1399
DI 10.1038/jid.2010.16
PG 9
WC Dermatology
SC Dermatology
GA 587EL
UT WOS:000276972300026
PM 20147963
ER
PT J
AU Basselin, M
Kim, HW
Chen, M
Ma, KZ
Rapoport, SI
Murphy, RC
Farias, SE
AF Basselin, Mireille
Kim, Hyung-Wook
Chen, Mei
Ma, Kaizong
Rapoport, Stanley I.
Murphy, Robert C.
Farias, Santiago E.
TI Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat
lipopolysaccharide model of neuroinflammation
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE eicosanoid; docosanoid; phospholipase A(2)
ID PHOSPHOLIPASE A(2); ACID METABOLISM; ALZHEIMERS-DISEASE;
INTRACEREBROVENTRICULAR INFUSION; LIPID MEDIATORS; GENE-EXPRESSION;
FATTY-ACID; INFLAMMATION; RESOLVINS; PATHWAYS
AB Neuroinflammation, caused by 6 days of intracerebroventricular infusion of a low dose of lipopolysaccharide (LPS; 0.5 ng/ h), stimulates brain arachidonic acid (AA) metabolism in rats, but 6 weeks of lithium pretreatment reduces this effect. To further understand this action of lithium, we measured concentrations of eicosanoids and docosanoids generated from AA and docosahexaenoic acid (DHA), respectively, in high-energy microwaved rat brain using LC/MS/MS and two doses of LPS. In rats fed a lithium-free diet, low (0.5 ng/h)- or high (250 ng/h)-dose LPS compared with artificial cerebrospinal fluid increased brain unesterified AA and prostaglandin E(2) concentrations and activities of AA-selective Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2))-IV and Ca(2+)-dependent secretory sPLA(2). LiCl feeding prevented these increments. Lithium had a significant main effect by increasing brain concentrations of lipoxygenase-derived AA metabolites, 5-hydroxyeicosatetraenoic acid (HETE), 5-oxo-eicosatetranoic acid, and 17-hydroxy- DHA by 1.8-, 4.3- and 1.9-fold compared with control diet. Lithium also increased 15-HETE in high-dose LPS-infused rats. Ca(2+)-independent iPLA(2)-VI activity and unesterified DHA and docosapentaenoic acid (22:5n-3) concentrations were unaffected by LPS or lithium. This study demonstrates, for the first time, that lithium can increase brain 17-hydroxy-DHA formation, indicating a new and potentially important therapeutic action of lithium.-Basselin, M., H-W. Kim, M. Chen, K. Ma, S. I. Rapoport, R. C. Murphy, and S. E. Farias. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation. J. Lipid Res.2010. 51: 1049-1056.
C1 [Basselin, Mireille; Kim, Hyung-Wook; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Murphy, Robert C.; Farias, Santiago E.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO USA.
RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM mirvasln@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health; National Institutes of Health [GM-069338]
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, the National Institutes of Health (M.B.,
H-W. K, M.C., K.M., and S.I.R.), and by LIPID MAPS Large Scale
Collaborative grant number GM-069338 from the National Institutes of
Health (R.C.M. and S.E.F.). Its contents are solely the responsibility
of the authors and do not necessarily represent the official views of
the National Institutes of Health or other granting agencies.
NR 65
TC 31
Z9 31
U1 1
U2 5
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 MAY
PY 2010
VL 51
IS 5
BP 1049
EP 1056
DI 10.1194/jlr.M002469
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 582XG
UT WOS:000276633100020
PM 20040630
ER
PT J
AU Cho, JY
Matsubara, T
Kang, DW
Ahn, SH
Krausz, KW
Idle, JR
Luecke, H
Gonzalez, FJ
AF Cho, Joo-Youn
Matsubara, Tsutomu
Kang, Dong Wook
Ahn, Sung-Hoon
Krausz, Kristopher W.
Idle, Jeffrey R.
Luecke, Hans
Gonzalez, Frank J.
TI Urinary metabolomics in Fxr-null mice reveals activated adaptive
metabolic pathways upon bile acid challenge
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE adaptive response; cholic acid; cortico-sterone; Cyp3a11; farnesoid X
receptor; lithocholic acid; metabolomics; p-cresol
ID FARNESOID-X-RECEPTOR; LITHOCHOLIC ACID; NUCLEAR RECEPTOR; LIVER
TOXICITY; DETOXIFICATION; ALPHA; CORTICOSTERONE; IDENTIFICATION;
ELIMINATION; OBSTRUCTION
AB Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3 alpha,6,7 alpha,12 alpha-tetrol (3 alpha,6,7 alpha,12 alpha-tetrahydroxy-5 beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.-Cho, J. Y., T. Matsubara, D. W. Kang, S. H. Ahn, K. W. Krausz, J. R. Idle, H. Luecke, and F. J. Gonzalez. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. J. Lipid Res. 2010. 51: 1063-1074.
C1 [Cho, Joo-Youn; Matsubara, Tsutomu; Ahn, Sung-Hoon; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague, Czech Republic.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
RI Cho, Joo-Youn/J-5672-2012;
OI Idle, Jeff/0000-0002-6143-1520
FU National Cancer Institute Intramural Research Program; Korea Health 21
R&D Project, Ministry of Health and Welfare, Republic of Korea [A03001];
United States Smokeless Tobacco Company
FX This work was supported by the National Cancer Institute Intramural
Research Program. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health. This work was also supported by Grant
A03001 (J.Y.C.) from the Korea Health 21 R&D Project, Ministry of Health
and Welfare, Republic of Korea and by a grant for collaborative research
(J.R.I.) from the United States Smokeless Tobacco Company.
NR 36
TC 22
Z9 22
U1 0
U2 5
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 MAY
PY 2010
VL 51
IS 5
BP 1063
EP 1074
DI 10.1194/jlr.M002923
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 582XG
UT WOS:000276633100022
PM 19965603
ER
PT J
AU Young, B
Levine, RJ
Salahuddin, S
Qian, C
Lim, KH
Karumanchi, SA
Rana, S
AF Young, Brett
Levine, Richard J.
Salahuddin, Saira
Qian, Cong
Lim, Kee-Hak
Karumanchi, S. Ananth
Rana, Sarosh
TI The use of angiogenic biomarkers to differentiate non-HELLP related
thrombocytopenia from HELLP syndrome
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Preeclampsia; angiogenic factors; thrombocytopenia
ID PLACENTAL GROWTH-FACTOR; TYROSINE KINASE-1; ONSET PREECLAMPSIA; SOLUBLE
ENDOGLIN; HYPERTENSION; DIAGNOSIS; MANAGEMENT; RISK
AB Methods. Serum was collected and the angiogenic biomarkers of patients with ITP and gestational thrombocytopenia (N = 9) were compared to patients with HELLP (N = 11) and PE (N = 11). Circulating levels of these angiogenic biomarkers were also compared by gestational age to 1564 randomly selected normotensive women from the Calcium for Preeclampsia Prevention study.
Results. Patients with non-HELLP thrombocytopenia had lower sFlt1 (7.3 +/- 3.8 ng/ml vs. 15.5 +/- 5 ng/ml, P < 0.001), lower sEng (8.7 +/- 3.6 vs. 34 +/- 17, P < 0.001) and higher PlGF (484 +/- 412 vs. 66.3 +/- 44, P = 0.003) than patients with HELLP syndrome. Angiogenic factor abnormalities in patients with PE were similar to patients with HELLP syndrome, suggesting a common pathogenesis. Patients with non-HELLP thrombocytopenia had angiogenic profiles similar to normotensive controls, whereas patients with HELLP syndrome had levels higher than the 90th percentile for sFlt1 and sEng and lower than the 10th percentile for PlGF.
Conclusions. Angiogenic biomarkers may be useful in excluding conditions that mimic PE.
C1 [Young, Brett; Salahuddin, Saira; Lim, Kee-Hak; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA.
[Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Qian, Cong] Glotech Inc, Rockville, MD USA.
[Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, 330 Brookline Ave,Kirstein 3812, Boston, MA 02215 USA.
EM saroshrana@gmail.com
FU NIH [WRHR 5k12HDOO1255]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX SR is supported by NIH grant WRHR 5k12HDOO1255. SAK is an investigator
of the Howard Hughes Medical Institute. RJL receives salary support from
the intramural research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 21
TC 24
Z9 25
U1 0
U2 1
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 MAY
PY 2010
VL 23
IS 5
BP 366
EP 370
DI 10.3109/14767050903184207
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 580PX
UT WOS:000276462500002
PM 19701867
ER
PT J
AU Calvo, E
Sanchez-Vargas, I
Kotsyfakis, M
Favreau, AJ
Barbian, KD
Pham, VM
Olson, KE
Ribeiro, JMC
AF Calvo, Eric
Sanchez-Vargas, Irma
Kotsyfakis, Michalis
Favreau, Amanda J.
Barbian, Kent D.
Pham, Van M.
Olson, Kenneth E.
Ribeiro, Jose M. C.
TI The Salivary Gland Transcriptome of the Eastern Tree Hole Mosquito,
Ochlerotatus triseriatus
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE mosquito; salivary gland; sialome; transcriptome; La Crosse virus
ID ADULT FEMALE MOSQUITO; VECTOR ANOPHELES-GAMBIAE; RICH SECRETORY
PROTEINS; AEDES-AEGYPTI; CODON VOLATILITY; BINDING-PROTEIN;
PLATELET-AGGREGATION; SEQUENCE ALIGNMENT; INSIGHT; SELECTION
AB Saliva of blood-sucking arthropods contains a complex mixture of peptides that affect their host's hemostasis, inflammation, and immunity. These activities can also modify the site of pathogen delivery and increase disease transmission. Saliva also induces hosts to mount an antisaliva immune response that can lead to skin allergies or even anaphylaxis. Accordingly, knowledge of the salivary repertoire, or sialome, of a mosquito is useful to provide a knowledge platform to mine for novel pharmacological activities, to develop novel vaccine targets for vector-borne diseases, and to develop epidemiological markers of vector exposure and candidate desensitization vaccines. The mosquito Ochlerotatus triseriatus is a vector of La Crosse virus and produces allergy in humans. In this work, a total of 1,575 clones randomly selected from an adult female O. triseriatus salivary gland cDNA library was sequenced and used to assemble a database that yielded 731 clusters of related sequences, 560 of which were singletons. Primer extension experiments were performed in selected clones to further extend sequence coverage, allowing for the identification of 159 protein sequences, 66 of which code for putative secreted proteins. Supplemental spreadsheets containing these data are available at http://exon.niaid.nih.gov/transcriptome/Ochlerotatus_triseriatus/S1/Ot-S1.xls and http://exon.niaid.nih.gov/transcriptome/Ochlerotatus_triseriatus/S2/Ot-S2.xls.
C1 [Calvo, Eric; Kotsyfakis, Michalis; Pham, Van M.; Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Sanchez-Vargas, Irma; Olson, Kenneth E.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Favreau, Amanda J.; Barbian, Kent D.] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect, Hamilton, MT 59840 USA.
RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM jribeiro@niaid.nih.gov
RI Kotsyfakis, Michail/G-9525-2014;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Ribeiro,
Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health [R01 AI46435]
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and National
Institutes of Health Grant R01 AI46435 to K.E.O.
NR 68
TC 9
Z9 9
U1 0
U2 5
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD MAY
PY 2010
VL 47
IS 3
BP 376
EP 386
DI 10.1603/ME09226
PG 11
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 595FV
UT WOS:000277597000012
PM 20496585
ER
PT J
AU Raizman, EA
Holland, JD
Keefe, LM
Moro, MH
AF Raizman, E. A.
Holland, J. D.
Keefe, L. M.
Moro, M. H.
TI Forest and Surface Water As Predictors of Borrelia burgdorferi and Its
Vector Ixodes scapularis (Acari: Ixodidae) in Indiana
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
ID LYME-DISEASE RISK; DAMMINI ACARI; UNITED-STATES; DEER TICK; HABITAT
SUITABILITY; LANDSCAPE; PATHOGENS; ABUNDANCE; FRAGMENTATION; INFECTION
AB The objective of this study was to assess whether the distribution of Borrelia burgdorferi, the causative agent of Lyme disease, and its vector tick Ixodes scapularis Say (Acari: Ixodidae) across Indiana is influenced by large-scale landscape features, specifically the proportion of forest within the surrounding landscape and the distance to water features such as lakes and major streams. Hunter-killed deer were checked for ticks in designated check-stations in the opening firearm hunting season between 2005 and 2007. Hunting locations for 3,600 deer were used in ArcGIS (ESRI, Redlands, CA) to examine the influence of forest and water features in the surrounding area on the occurrence of the tick and bacteria. In total, 82 of the 92 (89%) Indiana counties were sampled from 2005 to 2007. The proportion of tick-infested deer was 13.6, 15.8, and 25.5% in these years, respectively. There was a significant nonlinear response for I. scapularis to forest cover in 1 yr that indicated a greater probability of this tick presence at intermediate levels of forest area. Infested does were harvested in significantly more forested areas than bucks. No significant correlation was found neither between levels of forest area and B. burgdorferi nor between water bodies and both organisms.
C1 [Raizman, E. A.; Keefe, L. M.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Holland, J. D.] Purdue Univ, Coll Agr, Dept Entomol, W Lafayette, IN 47907 USA.
[Moro, M. H.] NIH, Div Comparat Med, Natl Ctr Res Resources, Bethesda, MD 20892 USA.
RP Raizman, EA (reprint author), Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
EM eraizman@purdue.edu
NR 50
TC 2
Z9 2
U1 0
U2 10
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
EI 1938-2928
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD MAY
PY 2010
VL 47
IS 3
BP 458
EP 465
DI 10.1603/ME09094
PG 8
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 595FV
UT WOS:000277597000021
PM 20496594
ER
PT J
AU Shukla, P
Faulk, KN
Emerson, SU
AF Shukla, Priyanka
Faulk, Kristina N.
Emerson, Suzanne U.
TI The Entire Core Protein of HCV JFH1 Is Required for Efficient Formation
of Infectious JFH1 Pseudoparticles
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE HCV pseudoparticles; core enhancement; viral glycoprotein assembly
ID HEPATITIS-C-VIRUS; B TYPE-I; CELL-CULTURE; ENVELOPE PROTEIN;
SUBCELLULAR-LOCALIZATION; E1 GLYCOPROTEIN; CHIMPANZEES; PARTICLES;
MUTATIONS; RECEPTOR
AB The vast majority of hepatitis C virus (HCV) strains cannot be grown in cell culture. Therefore, tests for neutralizing antibodies have relied heavily on retrovirus pseudoparticles displaying the envelope glycoproteins of HCV on their surface (HCVpp). Unfortunately, the envelope proteins of some strains, especially of JFH1, did not efficiently form functional HCVpp. We have manipulated the length and composition of the HCV core gene in the HCVpp expression vectors for three strains of HCV in an attempt to obtain more efficient production of pseudoparticles. The results demonstrated that the truncated core region included in the HCV expression plasmids of the classic pseudoparticle system was optimal for formation of strain H77pp, suboptimal for strain J6pp, and insufficient for strain JFH1pp. Efficiency of JFH1pp formation increased 20-fold when the truncated core gene was replaced with the entire core gene. The full core from J6 and HK had modest effect on the production of infectious J6 and HKpp. The data suggested that pairs of HCV glycoproteins differ inherently in their ability to associate into functional heterodimers and that the core protein, provided in cis as the beginning of the polyprotein product, can in some cases facilitate this process, possibly by increasing the rate of proper folding of the glycoproteins. J. Med. Virol. 82:783 790, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Shukla, Priyanka; Emerson, Suzanne U.] NIAID, Mol Hepatitis Sect, LID, NIH, Bethesda, MD 20892 USA.
[Faulk, Kristina N.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, LID, NIH, Bldg 50,Rm 6537,50 South Dr,MSC 8009, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health; Grant sponsor: National Institute of Allergy and Infectious
Diseases.
NR 26
TC 3
Z9 3
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD MAY
PY 2010
VL 82
IS 5
BP 783
EP 790
DI 10.1002/jmv.21660
PG 8
WC Virology
SC Virology
GA 578VK
UT WOS:000276324100008
PM 20336742
ER
PT J
AU Ding, D
Kanaly, CW
Bigner, DD
Cummings, TJ
Herndon, JE
Pastan, I
Raghavan, R
Sampson, JH
AF Ding, Dale
Kanaly, Charles W.
Bigner, Darrell D.
Cummings, Thomas J.
Herndon, James E., II
Pastan, Ira
Raghavan, Raghu
Sampson, John H.
TI Convection-enhanced delivery of free gadolinium with the recombinant
immunotoxin MR1-1
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Immunotoxins; Brain; Drug delivery systems glioblastoma; Gadolinium
ID GROWTH-FACTOR RECEPTOR; MALIGNANT GLIOMAS; REAL-TIME; INCREASED
EFFICACY; TARGETED TOXIN; DRUG-DELIVERY; PRIMATE BRAIN; RAT-BRAIN;
GLUCOCEREBROSIDASE; GLIOBLASTOMA
AB A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the BBB. MR1-1 is a novel recombinant immunotoxin that targets the GBM tumor-specific antigen EGFRvIII and can be delivered via CED infusion. However, drug distribution via CED varies dramatically, which necessitates active monitoring. Gadolinium conjugated to diethylenetriamine penta-acetic acid (Gd-DTPA) is a commonly used MRI contrast agent which can be co-infused with therapies using CED and may be useful in monitoring infusion leak and early distribution. Forty immunocompetent rats were implanted with intracerebral cannulas that were connected to osmotic pumps and subsequently randomized into four groups that each received 0.2% human serum albumin (HSA) mixed with a different experimental infusion: (1) 25 ng/ml MR1-1; (2) 0.1 mu mol/ml Gd-DTPA; (3) 25 ng/ml MR1-1 and 0.1 mu mol/ml Gd-DTPA; (4) 250 ng/ml MR1-1 and 0.1 mu mol/ml Gd-DTPA. The rats were monitored clinically for 6 weeks then necropsied and histologically assessed for CNS toxicity. All rats survived the entirety of the study without clinical or histological toxicity attributable to the study drugs. There was no statistically significant difference in weight change over time among groups (P > 0.999). MR1-1 co-infused with Gd-DTPA via CED is safe in the long-term setting in a pre-clinical animal model. Our data supports the use of Gd-DTPA, as a surrogate tracer, co-infused with MR1-1 for drug distribution monitoring in patients with GBM.
C1 [Sampson, John H.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Div Neurosurg,Dept Surg, Durham, NC 27710 USA.
[Ding, Dale] Duke Univ, Med Ctr, Sch Med, Durham, NC 27710 USA.
[Bigner, Darrell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Dept Pathol, Durham, NC 27710 USA.
[Herndon, James E., II] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Raghavan, Raghu] Therataxis LLC, Baltimore, MD 21218 USA.
RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Div Neurosurg,Dept Surg, Box 3050,220 Sands Bldg,Res Dr, Durham, NC 27710 USA.
EM dale.ding@duke.edu; charles.kanaly@duke.edu; bigne001@mc.duke.edu;
cummi008@mc.duke.edu; james.herndon@duke.edu; pastani@mail.nih.gov;
raghu@therataxis.com; john.sampson@duke.edu
FU National Center for Research Resources, National Institutes of Health
[TL1RR024126]; National Institutes of Health, National Cancer Institute,
Center for Cancer Research
FX We acknowledge the expert technical assistance provided by Gary Archer,
Tracy Chewning, and April Coan. This research was supported in part by
Duke University's CTSA grant TL1RR024126 from National Center for
Research Resources, National Institutes of Health and by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research.
NR 38
TC 28
Z9 28
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD MAY
PY 2010
VL 98
IS 1
BP 1
EP 7
DI 10.1007/s11060-009-0046-7
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 605LO
UT WOS:000278349300001
PM 19898744
ER
PT J
AU McFarland, H
AF McFarland, Henry
TI The importance of clinical trials in unraveling the mysteries of
multiple sclerosis
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 2nd International Conference on Advances in Clinical Neuroimmunology
CY MAY 31-JUN 01, 2010
CL Gdansk, POLAND
C1 [McFarland, Henry] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD MAY
PY 2010
VL 222
IS 1-2
BP 1
EP 2
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 603WR
UT WOS:000278239300002
ER
PT J
AU Ching, KH
Burbelo, PD
Carlson, PJ
Drevets, WC
Iadarola, MJ
AF Ching, Kathryn H.
Burbelo, Peter D.
Carlson, Paul J.
Drevets, Wayne C.
Iadarola, Michael J.
TI High levels of Anti-GAD65 and Anti-Ro52 autoantibodies in a patient with
major depressive disorder showing psychomotor disturbance
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE GAD65; Ro52; Depression; Autoimmunity; Psychomotor disturbance
ID BIPOLAR DISORDER; ANTIBODIES; SERA
AB Autoimmune disease and/or autoantibodies have been reported in mood disorder patients. We screened for autoantibodies to glutamic acid decarboxylase (GAD65), thyroid peroxidase (TPO), gastric H+/K+ ATPase (ATP4B), and Ro52 in a psychiatric patient cohort. A 24-year-old woman with major depressive disorder (MOD) with reduced psychomotor activity was identified with unusually high serum GAD65 and Ro52 autoantibody titers. Anti-GAD65 and anti-Ro52 autoantibodies were also elevated in the CSF from this patient. Longitudinal examination revealed a four-fold increase in anti-GAD65 serum antibody titers which correlated with exacerbation of psychomotor symptomatology. These results suggest the possibility that CNS autoimmunity may be responsible for the psychomotor impairment in this MOD patient. Published by Elsevier B.V.
C1 [Ching, Kathryn H.; Burbelo, Peter D.; Iadarola, Michael J.] NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
[Carlson, Paul J.; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA.
RP Ching, KH (reprint author), NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bldg 49,Room 1C20,49 Convent Dr, Bethesda, MD 20892 USA.
EM chingk@nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research, the National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, the National
Institutes of Health.
NR 16
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD MAY
PY 2010
VL 222
IS 1-2
BP 87
EP 89
DI 10.1016/j.jneuroim.2010.02.015
PG 3
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 603WR
UT WOS:000278239300043
PM 20227114
ER
PT J
AU Levy, DL
Coleman, MJ
Sung, H
Ji, F
Matthysse, S
Mendell, NR
Titone, D
AF Levy, Deborah L.
Coleman, Michael J.
Sung, Heejong
Ji, Fei
Matthysse, Steven
Mendell, Nancy R.
Titone, Debra
TI The genetic basis of thought disorder and language and communication
disturbances in schizophrenia
SO JOURNAL OF NEUROLINGUISTICS
LA English
DT Article
DE Schizophrenia; Thought disorder; Language disorders; Communication
disorders; Semantic anomalies; Genetics; Family studies; Linkage
analyses; Endophenotypes
ID AUTISM SPECTRUM DISORDER; LINKAGE ANALYSIS; FOLLOW-UP; COGNITIVE
DEFICITS; ROSCOMMON FAMILY; SPEECH DISORDER; PARENTS; FOXP2; IMPAIRMENT;
RISK
AB Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself. These findings suggest that deviant verbalizations may be more penetrant expressions of schizophrenia susceptibility genes than schizophrenia. This paper reviews the evidence documenting the presence of thought, language and communication disorders in schizophrenic patients and in their first-degree relatives. This familial aggregation potentially implicates genetic factors in the etiology of thought disorder, language anomalies, and communication disturbances in schizophrenia families. We also present two examples of ways in which thought, language and communication disorders can enrich genetic studies, including those involving schizophrenia. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Levy, Deborah L.; Coleman, Michael J.; Matthysse, Steven] McLean Hosp, Psychol Res Lab, Belmont, MA 02478 USA.
[Sung, Heejong] Natl Human Genome Res Inst, Genometr Sect, Inherited Dis Res Branch, NIH, Bethesda, MD USA.
[Ji, Fei] Stat Collaborat Inc, Washington, DC USA.
[Mendell, Nancy R.] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[Titone, Debra] McGill Univ, Dept Psychol, Montreal, PQ, Canada.
RP Levy, DL (reprint author), McLean Hosp, Psychol Res Lab, 115 Mill St, Belmont, MA 02478 USA.
EM dlevy@mclean.harvard.edu
FU NIMH [R01 MH071523, MH31340]; Sidney R. Baer, Jr. Foundation; Essel
Foundation; National Association for Research on Schizophrenia and
Depression
FX This study was supported in part by NIMH grants R01 MH071523 and
MH31340, the Sidney R. Baer, Jr. Foundation, the Essel Foundation, and
the National Association for Research on Schizophrenia and Depression.
NR 164
TC 35
Z9 37
U1 10
U2 25
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0911-6044
J9 J NEUROLINGUIST
JI J. Neurolinguist.
PD MAY
PY 2010
VL 23
IS 3
SI SI
BP 176
EP 192
DI 10.1016/j.jneuroling.2009.08.003
PG 17
WC Linguistics; Neurosciences; Psychology, Experimental
SC Linguistics; Neurosciences & Neurology; Psychology
GA 569AC
UT WOS:000275567200002
PM 20161689
ER
PT J
AU Elvevag, B
Foltz, PW
Rosenstein, M
DeLisi, LE
AF Elvevag, Brita
Foltz, Peter W.
Rosenstein, Mark
DeLisi, Lynn E.
TI An automated method to analyze language use in patients with
schizophrenia and their first-degree relatives
SO JOURNAL OF NEUROLINGUISTICS
LA English
DT Article
DE Discourse; Semantics; Schizophrenia; Latent semantic analysis
ID LATENT SEMANTIC ANALYSIS; CONSENSUS COGNITIVE BATTERY; COMMUNICATION
DISTURBANCES; SCHIZOAFFECTIVE DISORDER; RISK; SPEECH; FMRI; SIBLINGS;
LATERALIZATION; PHENOTYPES
AB Communication disturbances are prevalent in schizophrenia, and since it is a heritable illness these are likely present - albeit in a muted form - in the relatives of patients. Given the timeconsuming, and often subjective nature of discourse analysis, these deviances are frequently not assayed in large scale Studies. Recent work in computational linguistics and statistical-based semantic analysis has shown the potential and power of automated analysis of communication. We present an automated and objective approach to modeling discourse that detects very subtle deviations between probands, their first-degree relatives and unrelated healthy controls. Although these findings should be regarded as preliminary due to the limitations of the data at our disposal, we present a brief analysis of the models that best differentiate these groups in order to illustrate the utility of the method for future explorations of how language components are differentially affected by familial and illness related issues. Published by Elsevier Ltd.
C1 [Elvevag, Brita] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Foltz, Peter W.; Rosenstein, Mark] Pearson Knowledge Technol, Boulder, CO 80301 USA.
[Foltz, Peter W.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA.
[DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA USA.
[DeLisi, Lynn E.] Boston VA Healthcare Serv, Brockton, MA USA.
RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 3C104,MSC 1379, Bethesda, MD 20892 USA.
EM brita@elvevaag.net
FU NIMH
FX This research was Supported in part by the NIMH Intramural Research
Program.
NR 55
TC 15
Z9 15
U1 1
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0911-6044
J9 J NEUROLINGUIST
JI J. Neurolinguist.
PD MAY
PY 2010
VL 23
IS 3
SI SI
BP 270
EP 284
DI 10.1016/j.jneuroling.2009.05.002
PG 15
WC Linguistics; Neurosciences; Psychology, Experimental
SC Linguistics; Neurosciences & Neurology; Psychology
GA 569AC
UT WOS:000275567200008
PM 20383310
ER
PT J
AU Trembath, D
Rao, D
Morrison, J
Malarkey, D
AF Trembath, Dimitri
Rao, Deepa
Morrison, James
Malarkey, David
TI Comparative Pathology of Medulloblastoma in F-344 Rats and Humans
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 86th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 10-13, 2010
CL Philadelphia, PA
SP Amer Assoc Neuropathologists
C1 [Trembath, Dimitri] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Rao, Deepa; Malarkey, David] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Morrison, James] Chalk River Labs, Pathol Associates, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2010
VL 69
IS 5
MA 30
BP 528
EP 529
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 594WV
UT WOS:000277571500039
ER
PT J
AU Martin, S
Johnson, K
Steeg, P
Hattab, E
AF Martin, Sarah
Johnson, Karen
Steeg, Patricia
Hattab, Eyas
TI Clincopathologic and Immunohistochemical Characteristics of Metastatic
Breast Carcinoma to the Brain: A Series of 59 Cases
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 86th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 10-13, 2010
CL Philadelphia, PA
SP Amer Assoc Neuropathologists
C1 [Martin, Sarah] Indiana Univ, Sch Med, Dept Pathol, Bloomington, IN 47405 USA.
[Johnson, Karen; Hattab, Eyas] Indiana Univ, Sch Med, Dept Pathol & Lab Med, Bloomington, IN 47405 USA.
[Steeg, Patricia] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2010
VL 69
IS 5
MA 142
BP 558
EP 558
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 594WV
UT WOS:000277571500150
ER
PT J
AU Haselkorn, ML
Shellington, DK
Jackson, EK
Vagni, VA
Janesko-Feldman, K
Dubey, RK
Gillespie, DG
Cheng, DM
Bell, MJ
Jenkins, LW
Homanics, GE
Schnermann, J
Kochanek, PM
AF Haselkorn, M. Lee
Shellington, David K.
Jackson, Edwin K.
Vagni, Vincent A.
Janesko-Feldman, Keri
Dubey, Raghvendra K.
Gillespie, Delbert G.
Cheng, Dongmei
Bell, Michael J.
Jenkins, Larry W.
Homanics, Gregg E.
Schnermann, Jurgen
Kochanek, Patrick M.
TI Adenosine A(1) Receptor Activation as a Brake on the Microglial Response
after Experimental Traumatic Brain Injury in Mice
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE adenosine; A(1) receptor; BV-2 cells; head injury; Iba-1; knockout;
microglia; neurotrauma
ID CONTROLLED CORTICAL IMPACT; STATUS EPILEPTICUS; CEREBRAL-ISCHEMIA;
MOUSE-BRAIN; IN-VITRO; CELLS; RATS; NEURODEGENERATION; PROLIFERATION;
HIPPOCAMPUS
AB We reported that adenosine A(1) receptor (A(1)AR) knockout (KO) mice develop lethal status epilepticus after experimental traumatic brain injury (TBI), which is not seen in wild-type (WT) mice. Studies in epilepsy, multiple sclerosis, and neuro-oncology suggest enhanced neuro-inflammation and/or neuronal death in A(1)AR KO. We hypothesized that A(1)AR deficiency exacerbates the microglial response and neuronal damage after TBI. A1AR KO and WT littermates were subjected to mild controlled cortical impact (3m/sec; 0.5mm depth) to left parietal cortex, an injury level below the acute seizure threshold in the KO. At 24 h or 7 days, mice were sacrificed and serial sections prepared. Iba-1 immunostaining was used to quantify microglia at 7 days. To assess neuronal injury, sections were stained with Fluoro-Jade C (FJC) at 24 h to evaluate neuronal death in the hippocampus and cresyl violet staining at 7 days to analyze cortical lesion volumes. We also studied the effects of adenosine receptor agonists and antagonists on H-3-thymidine uptake (proliferation index) by BV-2 cells (immortalized mouse microglial). There was no neuronal death in CA1 or CA3 quantified by FJC. A(1)AR KO mice exhibited enhanced microglial response; specifically, Iba-1 + microglia were increased 20-50% more in A1AR KO versus WT in ipsilateral cortex, CA3, and thalamus, and contralateral cortex, CA1, and thalamus (p<0.05). However, contusion and cortical volumes did not differ between KO and WT. Pharmacological studies in cultured BV-2 cells indicated that A(1)AR activation inhibits microglial proliferation. A(1)AR activation is an endogenous inhibitor of the microglial response to TBI, likely via inhibition of proliferation, and this may represent a therapeutic avenue to modulate microglia after TBI.
C1 [Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA.
[Jackson, Edwin K.; Cheng, Dongmei; Homanics, Gregg E.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.
[Bell, Michael J.; Jenkins, Larry W.] Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15260 USA.
[Homanics, Gregg E.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15260 USA.
[Jackson, Edwin K.; Dubey, Raghvendra K.; Gillespie, Delbert G.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA.
[Schnermann, Jurgen] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Dubey, Raghvendra K.] Univ Zurich Hosp, Dept Obstet & Gynecol, Clin Reprod Endocrinol, Zurich, Switzerland.
RP Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, Safar Ctr Resuscitat Res, 3434 5th Ave, Pittsburgh, PA 15260 USA.
EM kochanekpm@ccm.upmc.edu
RI Kochanek, Patrick/D-2371-2015;
OI Homanics, Gregg/0000-0003-3641-8153; Kochanek,
Patrick/0000-0002-2627-913X; Shellington, David/0000-0001-6708-6978
FU NIH [NS 38087, NS 30318, DK 068575]; Swiss National Science Foundation
[32-64040.00, 320000-117998]; Oncosuisse [OCS-01551-08-2004]
FX We thank NIH NS 38087 (PMK), NS 30318 (PMK), DK 068575 (EKJ), Swiss
National Science Foundation #32-64040.00 (RKD), 320000-117998 (RKD), and
Oncosuisse OCS-01551-08-2004 (RKD) for support. We thank Marci Provins
and Cara Mulhollen for assisting with manuscript preparation.
NR 36
TC 35
Z9 35
U1 0
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAY
PY 2010
VL 27
IS 5
BP 901
EP 910
DI 10.1089/neu.2009.1075
PG 10
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 599LX
UT WOS:000277915400012
PM 20121416
ER
PT J
AU Anderson, CJ
Bulte, JWM
Chen, K
Chen, XY
Khaw, BA
Shokeen, M
Wooley, KL
VanBrocklin, HF
AF Anderson, Carolyn J.
Bulte, Jeff W. M.
Chen, Kai
Chen, Xiaoyuan
Khaw, Ban-An
Shokeen, Monica
Wooley, Karen L.
VanBrocklin, Henry F.
TI Design of Targeted Cardiovascular Molecular Imaging Probes
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE molecular imaging; bispecific antibodies; multimeric molecular imaging
agents; nanomaterials; superparamagnetic iron oxide; nanoparticles
ID POSITRON-EMISSION-TOMOGRAPHY; FATTY-ACID-METABOLISM; PROTEIN SURFACE
INTERACTIONS; IN-VIVO; MYOCARDIAL VIABILITY; STEM-CELLS; CELLULAR
THERAPEUTICS; COMPUTED TOMOGRAPHY; POLYETHYLENE OXIDE; CONTRAST AGENTS
AB Molecular imaging relies on the development of sensitive and specific probes coupled with imaging hardware and software to provide information about the molecular status of a disease and its response to therapy, which are important aspects of disease management. As genomic and proteomic information from a variety of cardiovascular diseases becomes available, new cellular and molecular targets will provide an imaging readout of fundamental disease processes. A review of the development and application of several cardiovascular probes is presented here. Strategies for labeling cells with superparamagnetic iron oxide nanoparticles enable monitoring of the delivery of stem cell therapies. Small molecules and biologics (e.g., proteins and antibodies) with high affinity and specificity for cell surface receptors or cellular proteins as well as enzyme substrates or inhibitors may be labeled with single-photon-emitting or positron-emitting isotopes for nuclear molecular imaging applications. Labeling of bispecific antibodies with single-photon-emitting isotopes coupled with a pretargeting strategy may be used to enhance signal accumulation in small lesions. Emerging nanomaterials will provide platforms that have various sizes and structures and that may be used to develop multimeric, multimodal molecular imaging agents to probe one or more targets simultaneously. These platforms may be chemically manipulated to afford molecules with specific targeting and clearance properties. These examples of molecular imaging probes are characteristic of the multidisciplinary nature of the extraction of advanced biochemical information that will enhance diagnostic evaluation and drug development and predict clinical outcomes, fulfilling the promise of personalized medicine and improved patient care.
C1 [VanBrocklin, Henry F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94107 USA.
[Anderson, Carolyn J.; Shokeen, Monica] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Bulte, Jeff W. M.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD USA.
[Chen, Kai; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Biomed Engn, NIH, Bethesda, MD USA.
[Khaw, Ban-An] Northeastern Univ, Dept Pharmaceut Sci, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Wooley, Karen L.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
[Wooley, Karen L.] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA.
RP VanBrocklin, HF (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Suite 350, San Francisco, CA 94107 USA.
EM Henry.vanbrocklin@radiology.ucsf.edu
RI Bulte, Jeff/A-3240-2008; Wooley, Karen/D-4399-2015
OI Bulte, Jeff/0000-0003-1202-1610; Wooley, Karen/0000-0003-4086-384X
FU Intramural NIH HHS [Z99 EB999999, ZII EB000066-01]
NR 66
TC 17
Z9 19
U1 0
U2 17
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 MAY
PY 2010
VL 51
SU 1
BP 3S
EP 17S
DI 10.2967/jnumed.109.068130
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 592XG
UT WOS:000277414600002
PM 20395345
ER
PT J
AU Xu, B
Hadj-Bouziane, F
Liu, N
Wilson, C
Tootell, R
Ungerleider, L
AF Xu, B.
Hadj-Bouziane, F.
Liu, N.
Wilson, C.
Tootell, R.
Ungerleider, L.
TI Amygdala lesions eliminate emotional modulatory feedback to the visual
cortex: a functional MRI study
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT Molecular Neuroimaging Symposium
CY MAY 06-07, 2010
CL NIH, Bethesda, MD
HO NIH
C1 [Xu, B.; Hadj-Bouziane, F.; Liu, N.; Tootell, R.; Ungerleider, L.] NIH, Bethesda, MD 20892 USA.
[Wilson, C.] Boston Univ, Boston, MA 02215 USA.
RI Hadj-Bouziane, Fadila/A-1180-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 1
PY 2010
VL 51
IS 5
MA 18
BP 833
EP 833
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 590PL
UT WOS:000277239000049
ER
PT J
AU Vasalatiy, O
Wu, CWH
Cheal, S
Tootell, RB
Koretsky, AP
Griffiths, GL
Ungerleider, L
AF Vasalatiy, O.
Wu, C. W. H.
Cheal, S.
Tootell, R. B.
Koretsky, A. P.
Griffiths, G. L.
Ungerleider, L.
TI Production and Preliminary Testing of Ultra-Stable
Gadolinium-Benzyl-DOTA-Cholera Toxin B Conjugates as MRI Brain Circuitry
Tracking Agents.
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT Molecular Neuroimaging Symposium
CY MAY 06-07, 2010
CL NIH, Bethesda, MD
HO NIH
C1 [Vasalatiy, O.; Wu, C. W. H.; Cheal, S.; Tootell, R. B.; Koretsky, A. P.; Griffiths, G. L.; Ungerleider, L.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 1
PY 2010
VL 51
IS 5
MA 23
BP 834
EP 834
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 590PL
UT WOS:000277239000054
ER
PT J
AU Novotny, JA
Harrison, DJ
Pawlosky, R
Flanagan, VP
Harrison, EH
Kurilich, AC
AF Novotny, Janet A.
Harrison, Dawn J.
Pawlosky, Robert
Flanagan, Vincent P.
Harrison, Earl H.
Kurilich, Anne C.
TI beta-Carotene Conversion to Vitamin A Decreases As the Dietary Dose
Increases in Humans
SO JOURNAL OF NUTRITION
LA English
DT Article
ID INTESTINAL-ABSORPTION; MASS-SPECTROMETRY; ADULT VOLUNTEER;
DOUBLE-TRACER; IN-VIVO; MEN; METABOLISM; TRIGLYCERIDES; EQUIVALENCE;
VARIABILITY
AB It has been suggested that high doses of beta-carotene limit its conversion to vitamin A, yet this effect has not been well established in humans. A feeding study was conducted in a randomized crossover design in which volunteers consumed 2 doses of deuterium-labeled beta-carotene on 2 occasions, with beta-carotene and vitamin A response assessed by plasma area under the concentration time curve (AUC). Seven volunteers (4 men, 3 women) consumed each of 2 doses of beta-carotene-d8 and provided serial blood samples for 37 d after each dose. beta-Carotene doses were 20 and 40 mg. Plasma beta-carotene-d8 was assessed by HPLC-MS. Plasma retinol (ROH)-d4, which was derived from the beta-carotene-d8, was evaluated by GC-MS after saponification to convert retinyl esters to ROH prior to the formation of the trimethylsilylether. The plasma AUC for beta-carotene-d8 increased 2-fold from the 20-mg dose to the 40-mg dose. The plasma AUC for ROH-d4 increased 36% from the 20-mg dose to the 40-mg dose. These results establish that, in humans, beta-carotene conversion to vitamin A decreases as the dietary dose increases. J. Nutr. 140: 915-918, 2010.
C1 [Novotny, Janet A.; Harrison, Dawn J.; Flanagan, Vincent P.] ARS, USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
[Pawlosky, Robert] NIH, Lab Metab Control, Bethesda, MD 20892 USA.
[Harrison, Earl H.] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA.
[Kurilich, Anne C.] PepsiCo, Barrington, IL 60010 USA.
RP Novotny, JA (reprint author), ARS, USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
EM janet.novotny@ars.usda.gov
FU USDA; NIH [R01DK044498, R01HL049879]
FX Supported by the USDA and NIH grants R01DK044498 and R01HL049879.
NR 25
TC 9
Z9 9
U1 0
U2 5
PU AMER SOC NUTRITIONAL SCIENCE
PI BETHESDA
PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2010
VL 140
IS 5
BP 915
EP 918
DI 10.3945/jn.109.116947
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 589CI
UT WOS:000277121800006
PM 20237064
ER
PT J
AU Mazariegos, M
Hambidge, KM
Westcott, JE
Solomons, NW
Raboy, V
Das, A
Goco, N
Kindem, M
Wright, LL
Krebs, NF
AF Mazariegos, Manolo
Hambidge, K. Michael
Westcott, Jamie E.
Solomons, Noel W.
Raboy, Victor
Das, Abhik
Goco, Norman
Kindem, Mark
Wright, Linda L.
Krebs, Nancy F.
TI Neither a Zinc Supplement nor Phytate-Reduced Maize nor Their
Combination Enhance Growth of 6-to 12-Month-Old Guatemalan Infants
SO JOURNAL OF NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL;
DEVELOPING-COUNTRIES; MOTOR DEVELOPMENT; POOLED ANALYSIS; CHILDREN;
DEFICIENCY; ABSORPTION; DIARRHEA; MORTALITY
AB After age 6 mo, the combination of breast-feeding and unfortified plant-based complementary feeding provides inadequate zinc (Zn). Additionally, high phytate intakes compromise the bioavailability of zinc. Our principal objective in this randomized controlled, doubly masked trial was to determine the effect of substituting low-phytate maize, a daily 5-mg zinc supplement, or both, in infants between ages 6-12 moon impaired linear growth velocity, a common feature of zinc deficiency. In the Western Highlands of Guatemala, 412 infants were randomized to receive low-phytate or control maize. Within each maize group, infants were further randomized to receive a zinc supplement or placebo. Length, weight, and head circumference were measured at 6, 9, and 12 mo of age. There were no significant differences between the 2 maize groups or between the Zn supplement and placebo groups and no treatment interaction was observed for length-for-age (LAZ), weight-for-length (WLZ) or head circumference Z-scores. Overall mean I SDI Z-scores at 6 mo for combined treatment groups were: LAZ, -2.1 +/- 1.1; WLZ, 0.7 +/- 1.0; and head circumference Z-score, -0.7.0 +/- 1.0. At 12 mo, these had declined further to: LAZ, -2.5 +/- 1.1; WLZ, -0.0 +/- 0.9; and head circumference Z-score, -0.9 +/- 1.1; 83.3% were stunted and 2% were wasted. Low linear growth in older Guatemalan infants was not improved with either low-phytate maize or a daily 5-mg zinc supplement. Low contribution of maize to the complementary food of the infants negated any potential advantage of feeding low-phytate maize. J. Nutr. 140: 1041-1048, 2010.
C1 [Mazariegos, Manolo; Solomons, Noel W.] Ctr Studies Sensory Impairments Aging & Metab, Guatemala City 01011, Guatemala.
[Hambidge, K. Michael; Westcott, Jamie E.; Krebs, Nancy F.] Univ Colorado Denver, Dept Pediat, Sect Nutr, Aurora, CO 80045 USA.
[Raboy, Victor] ARS, USDA, Aberdeen, ID 83210 USA.
[Das, Abhik; Goco, Norman; Kindem, Mark] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Wright, Linda L.] NICHHD, Rockville, MD 20852 USA.
RP Mazariegos, M (reprint author), Ctr Studies Sensory Impairments Aging & Metab, Guatemala City 01011, Guatemala.
EM michael.hambidge@ucdenver.edu
FU Global Network for Women's and Children's Health Research [NICHD U01
HD040657]; Bill and Melinda Gates Foundation; Office of Dietary
Supplements; NIH [K24 RR018357-01]
FX Supported by the Global Network for Women's and Children's Health
Research (NICHD U01 HD040657), the Bill and Melinda Gates Foundation,
the Office of Dietary Supplements, and NIH K24 RR018357-01.
NR 38
TC 24
Z9 24
U1 0
U2 0
PU AMER SOC NUTRITIONAL SCIENCE
PI BETHESDA
PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2010
VL 140
IS 5
BP 1041
EP 1048
DI 10.3945/jn.109.115154
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 589CI
UT WOS:000277121800025
PM 20335626
ER
PT J
AU Wan, RQ
Ahmet, I
Brown, M
Cheng, AW
Kamimura, N
Talan, M
Mattson, MP
AF Wan, Ruiqian
Ahmet, Ismayil
Brown, Martin
Cheng, Aiwu
Kamimura, Naomi
Talan, Mark
Mattson, Mark P.
TI Cardioprotective effect of intermittent fasting is associated with an
elevation of adiponectin levels in rats
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Apoptosis; Dietary energy restriction; Echocardiography; Inflammation;
Myocardial infarction
ID ISCHEMIA-REPERFUSION INJURY; ACTIVATED PROTEIN-KINASE; TERM CALORIC
RESTRICTION; MYOCARDIAL-INFARCTION; DIETARY RESTRICTION; NEUROTROPHIC
FACTOR; OXIDATIVE STRESS; DISEASE; HEART; NEUROENDOCRINE
AB It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction (MI) and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 h following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after MI. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. Published by Elsevier Inc.
C1 [Wan, Ruiqian; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Ahmet, Ismayil; Talan, Mark] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 27
TC 23
Z9 23
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD MAY
PY 2010
VL 21
IS 5
BP 413
EP 417
DI 10.1016/j.jnutbio.2009.01.020
PG 5
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 588FW
UT WOS:000277054500008
PM 19423320
ER
PT J
AU Qi, CF
Shin, DM
Li, Z
Wang, HS
Feng, JX
Hartley, JW
Fredrickson, TN
Kovalchuk, AL
Morse, HC
AF Qi, Chen-Feng
Shin, Dong-Mi
Li, Zhaoyang
Wang, Hongsheng
Feng, Jianxum
Hartley, Janet W.
Fredrickson, Torgny N.
Kovalchuk, Alexander L.
Morse, Herbert C., III
TI Anaplastic plasmacytomas: relationships to normal memory B cells and
plasma cell neoplasms of immunodeficient and autoimmune mice
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE plasmacytoma; anaplastic plasmacytoma; memory B cell; plasma cell;
oligonucleotide array
ID TRANSGENIC MOUSE MODEL; ISOTYPE SWITCH EVENTS; SRC FAMILY KINASES;
C-MYC; MULTIPLE-MYELOMA; EXPRESSION; GENE; TRANSLOCATIONS; ACTIVATION;
AID
AB Anaplastic plasmacytomas (APCTs) from NFS.V(+) congenic mice and pristane-induced plasmacytic PCTs from BALB/c mice were previously shown to be histologically and molecularly distinct subsets of plasma cell neoplasms (PCNs). Here we extended these comparisons, contrasting primary APCTs and PCTs by gene expression profiling in relation to the expression profiles of normal naive, germinal centre, and memory B cells and plasma cells. We also sequenced immunoglobulin genes from APCT and APCT-derived cell lines and defined surface phenotypes and chromosomal features of the cell lines by flow cytometry and by spectral karyotyping and fluorescence in situ hybridization. The results indicate that APCTs share many features with normal memory cells and the plasma cell-related neoplasms (PLs) of FASL-deficient mice, suggesting that APCTs and PLs are related and that both derive from memory B cells. Published in 2010 by John Wiley & Sons, Ltd.
C1 [Qi, Chen-Feng; Shin, Dong-Mi; Li, Zhaoyang; Wang, Hongsheng; Feng, Jianxum; Hartley, Janet W.; Fredrickson, Torgny N.; Kovalchuk, Alexander L.; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA.
RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Twinbrook 1,5640 Fishers Lane,Room 1421, Rockville, MD 20852 USA.
EM hmorse@niaid.nih.gov
OI Morse, Herbert/0000-0002-9331-3705
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank Alfonso
Macias for colony management and identification of tumour-bearing mice;
NIAID intramural editor Brenda Rae Marshall for assistance; and Nicole
McNeil, NCI, Genetics Branch for SKY interpretation.
NR 57
TC 6
Z9 6
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD MAY
PY 2010
VL 221
IS 1
BP 106
EP 116
DI 10.1002/path.2692
PG 11
WC Oncology; Pathology
SC Oncology; Pathology
GA 595RD
UT WOS:000277629100012
PM 20217872
ER
PT J
AU Salchow, DJ
Kohlhase, J
Miller, M
Kadom, N
FitzGibbon, EJ
Caruso, RC
Brooks, BP
AF Salchow, Daniel J.
Kohlhase, Juergen
Miller, Marijean
Kadom, Nadja
FitzGibbon, Edmond J.
Caruso, Rafael C.
Brooks, Brian P.
TI Absent Optic Chiasm Presenting With Horizontal Nystagmus
SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS
LA English
DT Article
ID TOWNES-BROCKS-SYNDROME; CONGENITAL NYSTAGMUS; HYPOPLASIA; ACHIASMA; MRI
AB A female infant with horizontal nystagmus and normal ophthalmic examination had isolated absence of the optic chiasm on magnetic resonance imaging. Eye movements were recorded on video and reviewed. Horizontal nystagmus without see-saw nystagmus was observed. Visual evoked potential showed inter-hemispheric asymmetry compatible with the absence of crossing chiasmal fibers. Systemic abnormalities in this patient included cleft lip, preauricular skin tags, broad thumbs, and an anteriorly positioned anus, suggestive of Townes-Brock syndrome. [J Pediatr Ophthalmol Strabismus 2010;47:187-191.]
C1 [Salchow, Daniel J.] Yale Univ, Sch Med, Dept Ophthalmol, New Haven, CT 06510 USA.
[Kohlhase, Juergen] Ctr Human Genet, Freiburg, Germany.
[Miller, Marijean; Brooks, Brian P.] Childrens Natl Med Ctr, Dept Ophthalmol, Washington, DC 20010 USA.
[Kadom, Nadja] Childrens Natl Med Ctr, Dept Neuroradiol, Washington, DC 20010 USA.
[FitzGibbon, Edmond J.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Caruso, Rafael C.; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
RP Salchow, DJ (reprint author), Yale Univ, Sch Med, Dept Ophthalmol, 40 Temple St,Suite 3D, New Haven, CT 06510 USA.
OI Kadom, Nadja/0000-0002-7073-956X
FU Research to Prevent Blindness, Inc., New York, New York
FX Daniel J. Salchow was supported in part by a departmental Challenge
Grant from Research to Prevent Blindness, Inc., New York, New York.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0191-3913
J9 J PEDIAT OPHTH STRAB
JI J. Pediatr. Ophthalmol. Strabismus.
PD MAY-JUN
PY 2010
VL 47
IS 3
BP 187
EP 191
DI 10.3928/01913913-20090818-08
PG 5
WC Ophthalmology; Pediatrics
SC Ophthalmology; Pediatrics
GA 598TZ
UT WOS:000277862900013
PM 20507004
ER
PT J
AU Schiffmann, R
Martin, RA
Reimschisel, T
Johnson, K
Castaneda, V
Lien, YH
Pastores, GM
Kampmann, C
Ries, M
Clarke, JTR
AF Schiffmann, Raphael
Martin, Rick A.
Reimschisel, Tyler
Johnson, Karen
Castaneda, Victoria
Lien, Y. Howard
Pastores, Gregory M.
Kampmann, Christoph
Ries, Markus
Clarke, Joe T. R.
TI Four-Year Prospective Clinical Trial of Agalsidase Alfa in Children with
Fabry Disease
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID ENZYME-REPLACEMENT THERAPY; BETA THERAPY; PEDIATRIC-PATIENTS;
MANIFESTATIONS; GLOBOTRIAOSYLCERAMIDE; GALACTOSIDASE; SAFETY;
ADOLESCENTS; NEUROPATHY; PHENOTYPE
AB Objectives To investigate a 4-year prospective clinical trial of agalsidase alfa in children with Fabry disease, an X-linked metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A.
Study design Seventeen (16 boys, 1 girl; age range, 7.3 to 18.4 years) of the 24 children who completed a 6-month, open-label agalsidase alfa study enrolled in a 3.5-year extension study that investigated the safety and potential efficacy of long-term treatment. All 17 patients completed the initial 6-month study, and 10 patients (9 boys) completed the extension study.
Results Agalsidase alfa was well tolerated. In treated boys, there were sustained, statistically-significant improvements in the clinical features of Fabry disease, including reduced plasma globotriaosylceramide levels, reduced pain severity assessed by the Brief Pain Index, and improved heart rate variability. Mean urine globotriaosylceramide levels were reduced to normal range (P < .05 compared with baseline during 1.5 to 4 years). Kidney function and left ventricular mass indexed to height remained stable throughout.
Conclusions This clinical trial demonstrates that treatment with agalsidase alfa was well tolerated and associated with improvement of Fabry disease-related features. (J Pediatr 2010;156:832-7).
C1 [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX 75226 USA.
[Schiffmann, Raphael; Ries, Markus] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Martin, Rick A.; Reimschisel, Tyler] Washington Univ, Sch Med, St Louis, MO USA.
[Johnson, Karen] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Castaneda, Victoria] E Tennessee Childrens Hosp, Knoxville, TN USA.
[Lien, Y. Howard] Arizona Hlth Sci Ctr, Tucson, AZ 85724 USA.
[Pastores, Gregory M.] NYU, Sch Med, New York, NY USA.
[Kampmann, Christoph] Univ Childrens Hosp, Mainz, Germany.
[Clarke, Joe T. R.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
RP Schiffmann, R (reprint author), Baylor Res Inst, Inst Metab Dis, 3812 Elm St, Dallas, TX 75226 USA.
EM Raphael.Schiffmann@baylorhealth.edu
OI Ries, Markus/0000-0002-5054-5741
FU Shire HGT; Genzyme Corporation; Amicus Therapeutics; ExSAR; Actelion;
Protalix; Biomarin
FX The study described in this report was a clinical trial conducted by
Shire Human Genetic Therapies, Inc. (HGT), which designed the study in
collaboration with the principal investigators and was responsible for
the collection and analysis of the data. R. S. has received research
funding, consultancy fees, and/or speaker's fees from Shire HGT,
Genzyme, and Amicus Therapeutics. J.T.R.C. has received research
funding, consultancy fees, and/or speaker's fees from Shire HGT,
Genzyme, ExSAR, and Actelion. M. R. is currently an employee of Shire
HGT. R. A. M. received research funding and consultancy fees from Shire
HGT and Genzyme during the course of this study and is now employed by
Shire HGT. G. M. P. received honoraria, travel grants, and/or research
support from Shire HGT, Genzyme, Protalix, and Biomarin. C. K. has
received research funding, consultancy fees, and/or speaker's fees from
Shire HGT and Genzyme Corporation. Y.H.L. has received research grants
from Shire HGT and Genzyme Corporation. The other authors declare no
conflicts of interest. The authors are responsible for the
interpretation presented in this report. R. S., G. M. P., Y.H.L., and
J.T.R.C. contributed to the first draft of the manuscript. All authors
have approved the final version of the manuscript and are fully
responsible for its content.
NR 31
TC 34
Z9 37
U1 0
U2 1
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 MAY
PY 2010
VL 156
IS 5
BP 832
EP U196
DI 10.1016/j.jpeds.2009.11.007
PG 7
WC Pediatrics
SC Pediatrics
GA 581LW
UT WOS:000276525600031
PM 20097359
ER
PT J
AU Hay, WW
Raju, TNK
Higgins, RD
Kalhan, SC
Devaskar, SU
AF Hay, William W., Jr.
Raju, Tonse N. K.
Higgins, Rosemary D.
Kalhan, Satish C.
Devaskar, Sherin U.
TI Research initiatives in neonatal hypoglycemia Reply
SO JOURNAL OF PEDIATRICS
LA English
DT Letter
C1 [Hay, William W., Jr.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
[Raju, Tonse N. K.; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Insititute Child Hlth, NIH, Bethesda, MD USA.
[Kalhan, Satish C.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Med, Cleveland, OH 44106 USA.
[Devaskar, Sherin U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Mattel Childrens Hosp UCLA, Los Angeles, CA 90095 USA.
RP Hay, WW (reprint author), Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAY
PY 2010
VL 156
IS 5
BP 863
EP 863
DI 10.1016/j.jpeds.2010.01.053
PG 1
WC Pediatrics
SC Pediatrics
GA 581LW
UT WOS:000276525600050
ER
PT J
AU Oh, KJ
Lee, SE
Jung, H
Kim, G
Romero, R
Yoon, BH
AF Oh, Kyung Joon
Lee, Si Eun
Jung, Hanna
Kim, Gilja
Romero, Roberto
Yoon, Bo Hyun
TI Detection of ureaplasmas by the polymerase chain reaction in the
amniotic fluid of patients with cervical insufficiency
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Amniotic fluid (AF); cervical insufficiency; chorioamnionitis;
intra-amniotic infection; intra-amniotic inflammation; polymerase chain
reaction (PCR); pregnancy; preterm birth; spontaneous abortion;
ureaplasmas
ID PRETERM PREMATURE RUPTURE; CLINICAL-SIGNIFICANCE; INTRAAMNIOTIC
INFECTION/INFLAMMATION; INTRAUTERINE INFECTION; MATRIX
METALLOPROTEINASE-8; MICROBIAL INVASION; MYCOPLASMA-HOMINIS; SPONTANEOUS
LABOR; PRELABOR RUPTURE; INTACT MEMBRANES
AB Aims: The purpose of this study was to determine the clinical significance of detecting microbial footprints of ureaplasmas in amniotic fluid (AF) using specific primers for the polymerase chain reaction (PCR) in patients presenting with cervical insufficiency.
Methods: Amniocentesis was performed in 58 patients with acute cervical insufficiency (cervical dilatation, >= 1.5 cm) and intact membranes, and without regular contractions (gestational age, 16-29 weeks). AF was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) were detected by PCR using specific primers. Patients were divided into three groups according to the results of AF culture and PCR for ureaplasmas: those with a negative AF culture and a negative PCR (n = 44), those with a negative AF culture and a positive PCR (n = 10), and those with a positive AF culture regardless of PCR result (n = 4).
Results: 1) Ureaplasmas were detected by PCR in 19.0% (11/58) of patients, by culture in 5.2% (3/58), and by culture and/or PCR in 22.4% (13/58); 2) Among the 11 patients with a positive PCR for ureaplasmas, the AF culture was negative in 91% (10/11); 3) Patients with a negative AF culture and a positive PCR for ureaplasmas had a significantly higher median AF matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count than those with a negative AF culture and a negative PCR (P < 0.001 and P < 0.05, respectively); 4) Patients with a positive PCR for ureaplasmas but a negative AF culture had a higher rate of spontaneous preterm birth within two weeks of amniocentesis than those with a negative AF culture and a negative PCR (P < 0.05 after adjusting for gestational age at amniocentesis); 5) Of the patients who delivered within two weeks of amniocentesis, those with a positive PCR for ureaplasmas and a negative AF culture had higher rates of histologic amnionitis and funisitis than those with a negative AF culture and a negative PCR (P < 0.05 after adjusting for gestational age at amniocentesis, for each); 6) However, no significant differences in the intensity of the intra-amniotic inflammatory response and perinatal outcome were found between patients with a positive AF culture and those with a negative AF culture and a positive PCR.
Conclusions: 1) Cultivation techniques for ureaplasmas did not detect most cases of intra-amniotic infection caused by these microorganisms (91% of cases with cervical insufficiency and microbial footprints for ureaplasmas in the amniotic cavity had a negative AF culture); 2) Patients with a negative AF culture and a positive PCR assay were at risk for intra-amniotic and fetal inflammation as well as spontaneous preterm birth.
C1 [Oh, Kyung Joon; Lee, Si Eun; Jung, Hanna; Kim, Gilja; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
EM Yoonbh@snu.ac.kr
RI Yoon, Bo Hyun/H-6344-2011
FU Korea government (Ministry of Education, Science and Technology)
[2009-0080429]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, DHHS
FX This research was supported in part by the National Research Foundation
of Korea (NRF) grant funded by the Korea government (Ministry of
Education, Science and Technology) (No. 2009-0080429) and in part by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 49
TC 57
Z9 59
U1 1
U2 3
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD MAY
PY 2010
VL 38
IS 3
BP 261
EP 268
DI 10.1515/JPM.2010.040
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 592NL
UT WOS:000277386100006
PM 20192887
ER
PT J
AU Madan, I
Romero, R
Kusanovic, JP
Mittal, P
Chaiworapongsa, T
Dong, Z
Mazaki-Tovi, S
Vaisbuch, E
Savasan, ZA
Yeo, L
Kim, CJ
Hassan, SS
AF Madan, Ichchha
Romero, Roberto
Kusanovic, Juan Pedro
Mittal, Pooja
Chaiworapongsa, Tinnakorn
Dong, Zhong
Mazaki-Tovi, Shali
Vaisbuch, Edi
Savasan, Zeynep Alpay
Yeo, Lami
Kim, Chong Jai
Hassan, Sonia S.
TI The frequency and clinical significance of intra-amniotic infection
and/or inflammation in women with placenta previa and vaginal bleeding:
an unexpected observation
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Chorioamnionitis; cytokines; deciduitis; idiopathic vaginal bleeding;
intra-amniotic inflammation; IL-6; prematurity; preterm delivery;
preterm labor
ID UNKNOWN ORIGIN; PRETERM LABOR; MYOMETRIAL CONTRACTIONS; LIPOXYGENASE
PRODUCTS; SMOOTH-MUSCLE; HUMAN DECIDUA; PREGNANCY; THROMBIN; 2ND-HALF;
RISK
AB Objective: Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor.
Study design: A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis.
Results: 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1-34.7 vs. 35.4 weeks, IQR: 33.9-36.9; P = 0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P = 0.008) than those without IAI.
Conclusions: Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h.
C1 [Madan, Ichchha; Romero, Roberto; Kusanovic, Juan Pedro; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Dong, Zhong; Mazaki-Tovi, Shali; Vaisbuch, Edi; Savasan, Zeynep Alpay; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Madan, Ichchha; Romero, Roberto; Kusanovic, Juan Pedro; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Vaisbuch, Edi; Savasan, Zeynep Alpay; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS.
NR 48
TC 28
Z9 30
U1 0
U2 2
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD MAY
PY 2010
VL 38
IS 3
BP 275
EP 279
DI 10.1515/JPM.2010.001
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 592NL
UT WOS:000277386100008
PM 20146660
ER
PT J
AU Mazaki-Tovi, S
Romero, R
Vaisbuch, E
Kim, SK
Kusanovic, JP
Chaiworapongsa, T
Mittal, P
Dong, Z
Pacora, P
Yeo, L
Hassan, SS
AF Mazaki-Tovi, Shali
Romero, Roberto
Vaisbuch, Edi
Kim, Sun Kwon
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Mittal, Pooja
Dong, Zhong
Pacora, Percy
Yeo, Lami
Hassan, Sonia S.
TI Evidence for differential regulation of the adipokine visfatin in the
maternal and fetal compartments in normal spontaneous labor at term
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Adipokine; body mass index (BMI); cord blood; cytokine; energy demands;
metabolism; neonate; obesity; overweight; parturition; pregnancy
ID COLONY-ENHANCING FACTOR; FREE FATTY-ACIDS; GESTATIONAL
DIABETES-MELLITUS; NORMAL HUMAN-PREGNANCY; GROWTH-FACTOR-I; ADIPONECTIN
CONCENTRATIONS; BIRTH-WEIGHT; INSULIN-RESISTANCE; ADIPOSE-TISSUE; SERUM
VISFATIN
AB Objective: Visfatin, a novel adipokine with metabolic and immunoregulatory properties, has been implicated in the regulation of fetal growth, as well as in preterm labor. A gap in knowledge is whether spontaneous labor at term is associated with changes in the maternal and fetal concentrations of visfatin. The aim of this study was to determine if the presence of labor at term is associated with alterations in maternal and neonatal plasma visfatin concentrations.
Study design: This cross-sectional study included 50 normal pregnant women at term and their appropriate-for-gestational age (AGA) neonates in the following groups: 1) 25 mother-neonate pairs delivered by elective cesarean section without spontaneous labor, and 2) 25 mother-neonate pairs who delivered vaginally following spontaneous labor. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.
Results: 1) The median visfatin concentration was higher in umbilical cord plasma of neonates born following a spontaneous labor at term than that of those who were born by an elective cesarean section (P = 0.02); 2) in contrast, the median maternal plasma visfatin concentration did not differ significantly between patients with and without labor (P = 0.44); and 3) there was a significant correlation between umbilical cord plasma concentration of visfatin and both maternal visfatin concentration (r = 0.54, P = 0.005) and gestational age (GA) at delivery (r = 0.58; P = 0.002) only in the absence of labor.
Conclusion: Term labor is associated with increased fetal, but not maternal, circulating visfatin concentrations. Previous reports indicate that preterm labor leading to preterm delivery is characterized by an increase in maternal plasma concentrations of visfatin. The observations reported herein support the view that there are fundamental differences in the endocrine and metabolic adaptations in normal labor at term and preterm labor.
C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kim, Sun Kwon; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Dong, Zhong; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH,
DHHS.
NR 107
TC 9
Z9 9
U1 0
U2 4
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
EI 1619-3997
J9 J PERINAT MED
JI J. Perinat. Med.
PD MAY
PY 2010
VL 38
IS 3
BP 281
EP 288
DI 10.1515/JPM.2010.045
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 592NL
UT WOS:000277386100009
PM 20146661
ER
PT J
AU Reinhardt, S
Zhao, M
Mnatsakanyan, A
Xu, LP
Ricklis, RM
Chen, A
Karp, JE
Rudek, MA
AF Reinhardt, Sarah
Zhao, Ming
Mnatsakanyan, Aleksander
Xu, Linping
Ricklis, Rebecca M.
Chen, Alice
Karp, Judith E.
Rudek, Michelle A.
TI A rapid and sensitive method for determination of veliparib (ABT-888),
in human plasma, bone marrow cells and supernatant by using LC/MS/MS
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE ABT-888; PARP inhibitor; LC/MS/MS; Pharmacokinetics; Veliparib
ID 0 CLINICAL-TRIAL; POLY(ADP-RIBOSE) POLYMERASE; INHIBITOR; PARP; MODELS
AB A rapid and sensitive method was developed and validated using a liquid chromatographic method with tandem mass spectrometry detection (LC/MS/MS) for determination of veliparib (ABT-888) in plasma, bone marrow supernatant, and bone marrow cells. Sample preparation involved a single protein precipitation step by the addition of the sample with acetonitrile. Separation of veliparib and the internal standard, A620223.69, was achieved on a Atlantis (TM) dC(18) column (1100 mm x 2.1 mm, 3 mu m) column using a mobile phase consisting of acetonitrile-ammonium acetate (2 mM) containing formic acid (0.1%, v/v) using isocratic flow at 0.2 mL/min for 3 min. The analyte and internal standard were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 5-1000 nM. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical methods. This method was Subsequently used to measure concentrations of veliparib in cancer patients receiving an oral daily dose of 10 mg with demonstration of drug accumulation in the marrow compartment and in the target leukemia bone marrow cells. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Reinhardt, Sarah; Zhao, Ming; Mnatsakanyan, Aleksander; Xu, Linping; Ricklis, Rebecca M.; Karp, Judith E.; Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA.
[Chen, Alice] NCI, Invest Drug Branch, CTEP, Rockville, MD 20892 USA.
RP Rudek, MA (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Bunting Blaustein Canc Res Bldg,Room 1M52,1650 Or, Baltimore, MD 21231 USA.
EM mrudek2@jhmi.edu
FU National Institutes of Health [P30CA069773, U01CA70095]
FX This work was supported by National Institutes of Health grants
P30CA069773 and U01CA70095.
NR 13
TC 4
Z9 4
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAY 1
PY 2010
VL 52
IS 1
BP 122
EP 128
DI 10.1016/j.jpba.2009.12.015
PG 7
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 553ID
UT WOS:000274358900018
PM 20071126
ER
PT J
AU Schneider, EH
Schnell, D
Strasser, A
Dove, S
Seifert, R
AF Schneider, Erich H.
Schnell, David
Strasser, Andrea
Dove, Stefan
Seifert, Roland
TI Impact of the DRY Motif and the Missing "Ionic Lock" on Constitutive
Activity and G-Protein Coupling of the Human Histamine H-4 Receptor
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID A(2A) ADENOSINE RECEPTOR; CRYSTAL-STRUCTURE; AMINO-ACID;
BETA(2)-ADRENERGIC RECEPTOR; STRUCTURAL INSTABILITY;
ADRENERGIC-RECEPTOR; GUINEA-PIG; ACTIVATION; RHODOPSIN; STATE
AB It is assumed that many G protein-coupled receptors (GPCRs) are restrained in an inactive state by the "ionic lock," an interaction between an arginine in transmembrane domain (TM) 3 (R3.50) and a negatively charged residue in TM6 (D/E6.30). In the human histamine H-4 receptor (hH(4)R), alanine is present in position 6.30. To elucidate whether this mutation causes the high constitutive activity of hH(4)R, we aimed to reconstitute the ionic lock by constructing the A6.30E mutant. The role of R3.50 was investigated by generating hH(4)R-R3.50A. Both mutants were expressed alone or together with G alpha(i2) and G beta(1)gamma(2) in Sf9 cells and characterized in GTPase, S-35-labeled guanosine 5'-[ gamma-thio] triphosphate binding, and high-affinity agonist binding assays. Unexpectedly, compared with hH(4)R, hH(4)R-A6.30E showed only nonsignificant reduction of constitutive activity and G protein-coupling efficiency. The K-D of [H-3] histamine was unaltered. By contrast, hH(4)R-R3.50A did not stimulate G proteins. Thioperamide affinity at hH(4)R-R3.50A was increased by 300 to 400%, whereas histamine affinity was reduced by approximately 50%. A model of the active hH(4)R state in complex with the G alpha(i2) C terminus was compared with the crystal structures of turkey beta(1) and human beta(2) adrenoceptors. We conclude that 1) constitutive activity of hH(4)R is facilitated by the salt bridge D5.69-R6.31 rather than by the missing ionic lock, 2) Y3.60 may form alternative locks in active and inactive GPCR states, 3) R3.50 is crucial for hH(4)R-G protein coupling, and 4) hH(4)R-R3.50A represents an inactive state with increased inverse agonist and reduced agonist affinity. Thus, the ionic lock, although stabilizing the inactive rhodopsin state, is not generally important for all class A GPCRs.
C1 [Schneider, Erich H.; Schnell, David] Univ Regensburg, Dept Pharmacol & Toxicol, Regensburg, Germany.
[Dove, Stefan] Univ Regensburg, Dept Pharmaceut Med Chem 2, Regensburg, Germany.
[Strasser, Andrea] Univ Regensburg, Dept Pharmaceut Med Chem 1, Regensburg, Germany.
[Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-3000 Hannover, Germany.
RP Schneider, EH (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N107,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM schneidere@mail.nih.gov
RI Schneider, Erich/B-9051-2016; Strasser, Andrea/F-9661-2016
OI Schneider, Erich/0000-0002-7905-4276;
FU Deutsche Forschungsgemeinschaft (DFG) [GRK 760]; International COST
Action [BM0806]
FX This work was supported by the Research Training Program
(Graduierten-kolleg) "Medicinal Chemistry-Ligand-Receptor Interactions"
of the Deutsche Forschungsgemeinschaft [Grant DFG GRK 760] and the
International COST Action BM0806.
NR 40
TC 33
Z9 33
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAY
PY 2010
VL 333
IS 2
BP 382
EP 392
DI 10.1124/jpet.109.163220
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584UE
UT WOS:000276777900004
PM 20106995
ER
PT J
AU Yang, KH
Galadari, S
Isaev, D
Petroianu, G
Shippenberg, TS
Oz, M
AF Yang, Keun-Hang
Galadari, Sehamuddin
Isaev, Dmytro
Petroianu, Georg
Shippenberg, Toni S.
Oz, Murat
TI The Nonpsychoactive Cannabinoid Cannabidiol Inhibits
5-Hydroxytryptamine(3A) Receptor-Mediated Currents in Xenopus laevis
Oocytes
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ACTIVATED K+ CURRENTS; HOUSE MUSK SHREW; 5-HT3 RECEPTOR; GANGLION
NEURONS; ANANDAMIDE; RESPONSES; CHANNELS; AGONISTS;
DELTA(9)-TETRAHYDROCANNABINOL; INVOLVEMENT
AB The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)(3A) receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 mu M)-evoked currents in a concentration-dependent manner (IC50 = 0.6 mu M). CBD (1 mu M) did not alter specific binding of the 5-HT3A antagonist [H-3]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl) propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 mu M CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 mu M, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 receptors. Neither intracellular BAPTA injection nor pertussis toxin pretreatment (5 mu g/ml) altered the CBD-evoked inhibition of 5-HT-induced currents. CBD inhibition was inversely correlated with 5-HT3A expression levels and mean 5-HT3 receptor current density. Pretreatment with actinomycin D, which inhibits protein transcription, decreased the mean 5-HT3 receptor current density and increased the magnitude of CBD inhibition. These data demonstrate that CBD is an allosteric inhibitor of 5-HT3 receptors expressed in X. laevis oocytes. They further suggest that allosteric inhibition of 5-HT3 receptors by CBD may contribute to its physiological roles in the modulation of nociception and emesis.
C1 [Oz, Murat] United Arab Emirates Univ, Dept Pharmacol, Fac Med & Hlth Sci, Lab Funct Lipid, Al Ain, U Arab Emirates.
[Galadari, Sehamuddin] United Arab Emirates Univ, Dept Biochem, Fac Med & Hlth Sci, Labs Cell Signaling, Al Ain, U Arab Emirates.
[Yang, Keun-Hang] Chapman Univ, Schmid Coll Sci, Dept Biol Sci, Orange, CA USA.
[Shippenberg, Toni S.; Oz, Murat] NIDA, Integrat Neurosci Sect, NIH, Baltimore, MD USA.
RP Oz, M (reprint author), United Arab Emirates Univ, Dept Pharmacol, Fac Med & Hlth Sci, Lab Funct Lipid, Al Ain, U Arab Emirates.
EM murat_oz@uaeu.ac.ae
RI Oz, Murat/E-2148-2012
FU National Institutes of Health National Institute on Drug Abuse; Faculty
of Medicine and Health Science, United Arab Emirates University
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Institute on Drug Abuse and
from the Faculty of Medicine and Health Science, United Arab Emirates
University.
NR 46
TC 22
Z9 23
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAY
PY 2010
VL 333
IS 2
BP 547
EP 554
DI 10.1124/jpet.109.162594
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584UE
UT WOS:000276777900021
PM 20160007
ER
PT J
AU Thompson, OM
Yaroch, AL
Moser, RP
Rutten, LJF
Agurs-Collins, T
AF Thompson, Olivia M.
Yaroch, Amy L.
Moser, Richard P.
Rutten, Lila J. Finney
Agurs-Collins, Tanya
TI School Vending Machine Purchasing Behavior: Results From the 2005
YouthStyles Survey
SO JOURNAL OF SCHOOL HEALTH
LA English
DT Article
DE child and adolescent health; nutrition and diet; growth and development
ID CHILDHOOD OBESITY; SECONDARY-SCHOOLS; FOOD ENVIRONMENT; HEALTH;
ADOLESCENTS; CHILDREN; ASSOCIATION; OVERWEIGHT; CANCER; INTERVENTION
AB METHODS: To evaluate the relationship between school vending machine purchasing behavior and school vending machine access and individual-level dietary characteristics, we used population-level YouthStyles 2005 survey data to compare nutrition-related policy and behavioral characteristics by the number of weekly vending machine purchases made by public school children and adolescents (N = 869). Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed using age- and race/ethnicity-adjusted logistic regression models that were weighted on age and sex of child, annual household income, head of household age, and race/ethnicity of the adult in study. Data were collected in 2005 and analyzed in 2008.
RESULTS: Compared to participants who did not purchase from a vending machine, participants who purchased >= 3 days/week were more likely to (1) have unrestricted access to a school vending machine (OR = 1.71; 95% CI = 1.13-2.59); (2) consume regular soda and chocolate candy >= 1 time/day (OR = 3.21; 95% CI = 1.87-5.51 and OR = 2.71; 95% CI = 1.34-5.46, respectively); and (3) purchase pizza or fried foods from a school cafeteria >= 1 day/week (OR = 5.05; 95% CI = 3.10-8.22).
CONCLUSIONS: Future studies are needed to establish the contribution that the school-nutrition environment makes on overall youth dietary intake behavior, paying special attention to health disparities between whites and nonwhites.
C1 [Thompson, Olivia M.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68198 USA.
[Yaroch, Amy L.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68105 USA.
[Yaroch, Amy L.] Univ Nebraska Med Ctr, Coll Publ Hlth, Ctr Human Nutr, Omaha, NE 68105 USA.
[Moser, Richard P.; Agurs-Collins, Tanya] NCI, DCCPS, NIH, Bethesda, MD 20892 USA.
[Rutten, Lila J. Finney] NCI, Clin Monitoring Res Program, Hlth Commun & Informat Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Thompson, OM (reprint author), Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68198 USA.
EM othompson@unmc.edu; ayaroch@cfhnutrition.org; moserr@mail.nih.gov;
finneyl@mail.nih.gov; collinsta@mail.nih.gov
NR 40
TC 5
Z9 5
U1 2
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-4391
J9 J SCHOOL HEALTH
JI J. Sch. Health
PD MAY
PY 2010
VL 80
IS 5
BP 225
EP 232
PG 8
WC Education & Educational Research; Education, Scientific Disciplines;
Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Education & Educational Research; Health Care Sciences & Services;
Public, Environmental & Occupational Health
GA 585WX
UT WOS:000276862200003
PM 20529195
ER
PT J
AU Rishi, V
Oh, WJ
Heyerdahl, SL
Zhao, JF
Scudiero, D
Shoemaker, RH
Vinson, C
AF Rishi, Vikas
Oh, Won-Jun
Heyerdahl, Sarah L.
Zhao, Jianfei
Scudiero, Dominic
Shoemaker, Robert H.
Vinson, Charles
TI 12 Arylstibonic acids that inhibit the DNA binding of five B-ZIP dimers
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Arylstibonic acids; DNA binding; B-ZIP domain; Leucine zipper; Antimony;
Small-molecule inhibitors
ID PROTEIN-PROTEIN INTERACTIONS; TRANSCRIPTION FACTORS; DIMERIZATION
SPECIFICITY; COILED-COIL; CANCER; REGION; DOMAIN; JUN; TOPOISOMERASE;
TUMORIGENESIS
AB Previously, we identified an arylstibonic acid, NSC13778 that specifically binds to the basic region of the C/EBP alpha B-ZIP domain and disrupts DNA binding. We now examine a panel of 14 additional arylstibonic acid derivatives of NSC13778 for their ability to inhibit the DNA binding of five B-ZIP dimers (c-Fos vertical bar JunD, VBP, C/EBR alpha, C/EBP beta, and CREB). They show various specificities at inhibiting the DNA binding of five B-ZIP domains. NSC13746 inhibits the DNA binding of C/EBP beta and CREB at 100 nM and promiscuously inhibiting the DNA binding of all five proteins in the 1 mu M range. Dialysis experiments indicate that NSC 13746 binding to the B-ZIP domain is reversible. Thermal denaturation studies indicate that NSC13746 binds the B-ZIP domain. Some compounds specifically inhibit DNA binding, with VBP and c-Fos vertical bar JunD being most easily disrupted. These compounds inhibit, with similar specificities to the pure B-ZIP domains, the DNA binding of nuclear extract to the AP1 DNA sequence but no inhibition is observed to SP1 containing oligonucleotide. Transient transfection assays indicate that NSC13746 can inhibit the TPA induced activation of two B-ZIP dependent reporters. These experiments suggest that arylstibonic acids are promising leads for inhibiting the DNA binding of a group of B-ZIP proteins in cells. Published by Elsevier Inc.
C1 [Rishi, Vikas; Oh, Won-Jun; Heyerdahl, Sarah L.; Zhao, Jianfei; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Scudiero, Dominic] SAIC, Frederick, MD 21702 USA.
[Shoemaker, Robert H.] NCI, Dev Therapeut Program, DCTD, Frederick, MD 21702 USA.
RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3128, Bethesda, MD 20892 USA.
EM Vinsonc@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health. 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 42
TC 9
Z9 9
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD MAY
PY 2010
VL 170
IS 2
SI SI
BP 216
EP 225
DI 10.1016/j.jsb.2010.02.013
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 589XZ
UT WOS:000277188800006
PM 20176111
ER
PT J
AU Linkenhoker, JR
Burkholder, TH
Linton, CGG
Walden, A
Abusakran-Monday, KA
Rosero, AP
Foltz, CJ
AF Linkenhoker, Jan R.
Burkholder, Tanya H.
Linton, C. G. Garry
Walden, April
Abusakran-Monday, Kim A.
Rosero, Ana P.
Foltz, Charmaine J.
TI Effective and Safe Anesthesia for Yorkshire and Yucatan Swine with and
without Cardiovascular Injury and Intervention
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID FENTANYL ANESTHESIA; TELAZOL-XYLAZINE; LABORATORY PIGS; MIDAZOLAM;
MEDETOMIDINE; KETAMINE; COMBINATION; CARDIOPULMONARY; ATIPAMEZOLE;
DROPERIDOL
AB The goal of this study was to identify an injectable anesthetic protocol that provides sedation sufficient for peripheral vascular catheterization, intubation, and transport while minimizing cardiovascular changes in Yorkshire and Yucatan pigs with and without cardiovascular injury and intervention (CI). Phase 1 examined the safety and efficacy of acepromazine-ketamine, diazepam-ketamine, midazolam-ketamine, and medetomidine-ketamine in 5 healthy Yorkshire pigs. For each drug combination, we obtained multiple measurements of heart rate, blood pressure, respiratory rate, temperature, sedation score, ability to catheterize and intubate, and recovery score. Phase 2 evaluated and refined the dose of the most effective Phase 1 anesthetic combination (midazolam-ketamine) in healthy and CI Yorkshire pigs (n = 53 trials). Phase 3 mirrored Phase 2 but tested midazolam-ketamine in healthy and CI Yucatan pigs (n = 34 trials). Midazolam (0.5 mg/kg)-ketamine (25 to 27 mg/kg) was the most effective anesthetic combination in healthy Yorkshire pigs, but this dose was less effective in healthy Yucatan pigs and CI Yorkshire and Yucatan pigs. Midazolam-ketamine resulted in tachycardia and apnea more frequently in CI pigs than healthy pigs. This combination also caused vomiting in one CI Yucatan pig. Overall, midazolam-ketamine provided safe and effective sedation for catheterization and intubation of both healthy and CI pigs. This study suggests Yucatan pigs may require a higher dose midazolam-ketamine to achieve the same level of sedation as that in Yorkshire pigs. Although anesthetic complication rates were higher in CI pigs, our results indicate that midazolam-ketamine can be safely used for sedation of both pig breeds with and without CI.
C1 [Linkenhoker, Jan R.; Burkholder, Tanya H.; Linton, C. G. Garry; Walden, April; Abusakran-Monday, Kim A.; Rosero, Ana P.; Foltz, Charmaine J.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
RP Linkenhoker, JR (reprint author), NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
EM linkenhj@od.nih.gov
FU NIH Division of Veterinary Resources
FX This research was supported by the Intramural Research Program of the
NIH Division of Veterinary Resources. The views and opinions provided
are those of the authors and do not reflect the official policy or
positions of the NIH, Department of Health and Human Services, or United
States Government.
NR 28
TC 10
Z9 11
U1 0
U2 1
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD MAY
PY 2010
VL 49
IS 3
BP 344
EP 351
PG 8
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 599FA
UT WOS:000277895200016
PM 20587167
ER
PT J
AU Rethman, MP
Carpenter, W
Cohen, EEW
Epstein, J
Evans, CA
Flaitz, CM
Graham, FJ
Hujoel, PP
Kalmar, JR
Koch, WM
Lambert, PM
Lingen, MW
Oettmeier, BW
Patton, LL
Perkins, D
Reid, BC
Sciubba, JJ
Tomar, SL
Wyatt, AD
Aravamudhan, K
Frantsve-Hawley, J
Cleveland, JL
Meyer, DM
AF Rethman, Michael P.
Carpenter, William
Cohen, Ezra E. W.
Epstein, Joel
Evans, Caswell A.
Flaitz, Catherine M.
Graham, Frank J.
Hujoel, Philippe P.
Kalmar, John R.
Koch, Wayne M.
Lambert, Paul M.
Lingen, Mark W.
Oettmeier, Bert W., Jr.
Patton, Lauren L.
Perkins, David
Reid, Britt C.
Sciubba, James J.
Tomar, Scott L.
Wyatt, Alfred D., Jr.
Aravamudhan, Krishna
Frantsve-Hawley, Julie
Cleveland, Jennifer L.
Meyer, Daniel M.
CA Amer Dent Assoc Council Sci
TI Evidence-based clinical recommendations regarding screening for oral
squamous cell carcinomas
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE American Dental Association (ADA); biopsy; brush; cancer; carcinoma;
squamous cell; evidence-based dentistry; mouth neoplasms; oral cancer;
practice guidelines
ID UPPER AERODIGESTIVE TRACT; HUMAN-PAPILLOMAVIRUS; TOLUIDINE BLUE;
NECK-CANCER; HEAD; METAANALYSIS; LESIONS; CHEMILUMINESCENCE; DYSPLASIA;
VISUALIZATION
AB Background. This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions.
Types of Studies Reviewed. The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected five systematic reviews and four clinical studies to use as a basis for developing recommendations.
Results. The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care.
Clinical Implications. The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.
C1 [Aravamudhan, Krishna; Frantsve-Hawley, Julie] Amer Dent Assoc, Ctr Evidence Based Dent, Div Sci, Chicago, IL 60611 USA.
[Rethman, Michael P.] Univ Maryland, Baltimore Coll Dent Surg, Baltimore, MD USA.
[Carpenter, William] Univ Pacific, Arthur A Dugoni Sch Dent, Dept Pathol & Med, San Francisco, CA USA.
[Cohen, Ezra E. W.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA.
[Epstein, Joel] Univ Illinois, Coll Dent, Dept Oral Med & Diagnost Sci, Chicago, IL USA.
[Epstein, Joel] Univ Illinois, Coll Med, Dept Otolaryngol Head & Neck Surg, Chicago, IL USA.
[Epstein, Joel] Univ Illinois, Ctr Canc, Chicago, IL USA.
[Flaitz, Catherine M.] Univ Texas Dent Branch, Dept Diagnost Sci, Houston, TX USA.
[Flaitz, Catherine M.] Univ Texas Dent Branch, Dept Pediat Dent, Houston, TX USA.
[Graham, Frank J.] Montefiore Med Ctr, Dept Dent, Bronx, NY 10467 USA.
[Hujoel, Philippe P.] Univ Washington, Sch Dent, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA.
[Koch, Wayne M.] Univ Maryland, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
[Lambert, Paul M.] Dept Vet Affairs Med Ctr, Boise, ID USA.
[Lingen, Mark W.] Univ Chicago, Med Ctr, Dept Pathol, Chicago, IL 60637 USA.
[Patton, Lauren L.] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA.
[Reid, Britt C.] NCI, Modifiable Risk Factors Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Sciubba, James J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Tomar, Scott L.] Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, Gainesville, FL USA.
[Wyatt, Alfred D., Jr.] Med Coll Georgia, Sch Dent, Atlanta, GA USA.
[Kalmar, John R.] Ohio State Univ, Coll Dent, Div Oral & Maxillofacial Surg Pathol & Anesthesio, Columbus, OH 43210 USA.
[Frantsve-Hawley, Julie] Amer Dent Assoc, Res Inst, Chicago, IL 60611 USA.
[Cleveland, Jennifer L.] Ctr Dis Control & Prevent, Surveillance Invest & Res Branch, Div Oral Hlth, Chamblee, GA USA.
RP Aravamudhan, K (reprint author), Amer Dent Assoc, Ctr Evidence Based Dent, Div Sci, 211 E Chicago Ave, Chicago, IL 60611 USA.
EM aravamudhank@ada.org
OI Patton, Lauren/0000-0002-8253-4588
NR 51
TC 103
Z9 111
U1 1
U2 12
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD MAY
PY 2010
VL 141
IS 5
BP 509
EP 520
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 594KV
UT WOS:000277537500017
PM 20436098
ER
PT J
AU Yaffe, K
Lindquist, K
Vittinghoff, E
Barnes, D
Simonsick, EM
Newman, A
Satterfield, S
Rosano, C
Rubin, SM
Ayonayon, HN
Harris, T
AF Yaffe, Kristine
Lindquist, Karla
Vittinghoff, Eric
Barnes, Deborah
Simonsick, Eleanor M.
Newman, Anne
Satterfield, Suzanne
Rosano, Caterina
Rubin, Susan M.
Ayonayon, Hilsa N.
Harris, Tamara
CA Hlth Aging & Body Compsition Study
TI The Effect of Maintaining Cognition on Risk of Disability and Death
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cognition; cognitive maintenance; mortality; disability
ID INDIVIDUAL-DIFFERENCES; OLDER-ADULTS; DECLINE; IMPAIRMENT; AGE;
DEMENTIA; TRAJECTORIES; PERFORMANCE; MORTALITY; RATS
AB OBJECTIVES
To determine whether long-term maintenance of cognition is associated with health advantages such as lower mortality or incident disability in older adults.
DESIGN
Longitudinal cohort study.
SETTING
Community clinics at two sites.
PARTICIPANTS
Two thousand seven hundred thirty-three adults with a mean age of 74 at baseline and 80 at follow-up.
MEASUREMENTS
Cognitive function was assessed using the Modified Mini-Mental State Examination (3MS), a test of global cognition, at least two times. Three cognitive groups were defined based on 4-year participant-specific slopes (maintainers, slopes of >= 0; minor decliners, slopes < 0 but no more than 1 standard deviation (SD) below the mean; major decliners, slopes > 1 SD below the mean). Whether the cognitive groups differed in mortality and incident disability during the subsequent 3 years was determined.
RESULTS
Nine hundred eighty-four (36%) participants were maintainers, 1,314 (48%) were minor decliners, and 435 (16%) were major decliners. Maintainers had lower mortality (7% vs 14%, hazard ratio (HR)=0.48, 95% confidence interval (CI)=0.36-0.63) and incident disability (22% vs 29%, HR=0.74, 95% CI=0.62-0.89) than minor decliners. After adjustment for age, race, sex, education, apolipoprotein E epsilon 4, depression, body mass index, stroke, hypertension, and diabetes mellitus, these differences remained. As expected, major decliners had greater mortality (20%) and incident disability (40%) than minor decliners.
CONCLUSION
A substantial proportion of older adults maintain cognitive function in their eighth and ninth decades of life. These older adults demonstrate lower risk of death and functional decline than those with minor cognitive decline, supporting the concept of "successful" cognitive aging.
C1 [Yaffe, Kristine; Barnes, Deborah] Univ Calif San Francisco, Dept Psychiat, Sch Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Sch Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Vittinghoff, Eric; Rubin, Susan M.; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94121 USA.
[Lindquist, Karla] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Newman, Anne; Rosano, Caterina] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Harris, Tamara] NIA, Dept Epidemiol, Demog & Biometry Program, Bethesda, MD 20892 USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Sch Med, Box 181,4150 Clement St, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institutes of Health, National Institute on Aging;
[AG-6-2101]; [AG-6-2103]; [AG-6-2106]; [AG021918]; [AG031155]
FX Conflict of Interest: The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the
authors have no financial or any other kind of personal conflicts with
this paper.; Funded by Grants AG-6-2101, AG-6-2103, AG-6-2106, and
AG021918. This research was supported in part by the Intramural Research
Program of the National Institutes of Health, National Institute on
Aging. Dr. Yaffe was supported in part by AG031155 and an anonymous
foundation.; Author Contributions: Study concept and design: KY, KL, EV,
DB. Acquisition of subjects and data: ES, AN, SS, SR, HA, TH. Analysis
and interpretation of data: KY, KL, EV, DB, ES, AN, SS, CR, SR, HA, TH.
Preparation of manuscript: KY, KL, EV, DB, ES, AN, SS, CR, SR, HA, TH).;
Sponsor's Role: The National Institute on Aging played a role in
overseeing study performance and data collection.
NR 24
TC 33
Z9 33
U1 1
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2010
VL 58
IS 5
BP 889
EP 894
DI 10.1111/j.1532-5415.2010.02818.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 592XE
UT WOS:000277414400013
PM 20406308
ER
PT J
AU Alexander, NB
Taffet, GE
Horne, FM
Eldadah, BA
Ferrucci, L
Nayfield, S
Studenski, S
AF Alexander, Neil B.
Taffet, George E.
Horne, Frances McFarland
Eldadah, Basil A.
Ferrucci, Luigi
Nayfield, Susan
Studenski, Stephanie
TI Bedside-to-Bench Conference: Research Agenda for Idiopathic Fatigue and
Aging
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE fatigue; energy utilization; mitochondria; muscle
ID HUMAN SKELETAL-MUSCLE; CANCER-RELATED FATIGUE; ADENINE-NUCLEOTIDE
TRANSLOCATOR; MAGNETIC-RESONANCE-SPECTROSCOPY; CHRONIC HEART-FAILURE;
MITOCHONDRIAL DYSFUNCTION; REUPTAKE INHIBITION; PHYSICAL-ACTIVITY;
IN-VIVO; PLASMA-CONCENTRATIONS
AB Fatigue is a symptom that older persons, especially by those with chronic diseases, frequently experience. Definitions and prevalence of fatigue may vary across studies, across diseases, and even between investigators and patients. The focus of this review is on physical fatigue, recognizing that there are other related domains of fatigue (such as cognitive fatigue).
Many definitions of fatigue involve a sensation of "low" energy, suggesting that fatigue could be a disorder of energy balance. Poor energy utilization efficiency has not been considered in previous studies but is likely to be one of the most important determinants of fatigue in older individuals. Relationships between activity level, capacity for activity, a tolerable rate of activity, and a tolerable fatigue threshold or ceiling underlie a notion of fatiguability. Mechanisms probably contributing to fatigue in older adults include decline in mitochondrial function, alterations in brain neurotransmitters, oxidative stress, and inflammation. The relationships between muscle function and fatigue are complex. A number of diseases (such as cancer) are known to cause fatigue and may serve as models for how underlying impaired physiological processes contribute to fatigue, particularly those in which energy utilization may be an important factor. A further understanding of fatigue will require two key strategies: to develop and refine fatigue definitions and measurement tools and to explore underlying mechanisms using animal and human models.
C1 [Alexander, Neil B.] Univ Michigan Hosp & Vet Affairs Ann Arbor, Hlth Care Syst Geriatr Res Educ & Clin Ctr, Mobil Res Ctr, Geriatr Ctr, Ann Arbor, MI USA.
[Alexander, Neil B.] Univ Michigan Hosp & Vet Affairs Ann Arbor, Hlth Care Syst Geriatr Res Educ & Clin Ctr, Div Geriatr Med, Ann Arbor, MI USA.
[Taffet, George E.] Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA.
[Horne, Frances McFarland] Amer Geriatr Soc, New York, NY USA.
[Eldadah, Basil A.; Nayfield, Susan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Bethesda, MD 20892 USA.
[Studenski, Stephanie] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Studenski, Stephanie] Pittsburgh Healthcare Ctr, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
RP Alexander, NB (reprint author), VA Ann Arbor Hlth Care Syst GRECC, 2215 Fuller Rd, Ann Arbor, MI 48105 USA.
EM nalexand@med.umich.edu
FU American Geriatrics Society; National Institute on Aging [AG02830]; John
A. Hartford Foundation; National Institutes of Health (NIH) [P30
AG024824, P30 AG024827, K24 AG019675, K07 AG023641, P20 CA103730];
Department of Veterans Affairs; National Institute on Aging, NIH,
Baltimore, Maryland
FX The conference organizers wish to thank the American Geriatrics Society,
the National Institute on Aging (R13 grant AG02830), and the John A.
Hartford Foundation for their generous support. The coauthors also
acknowledge support from National Institutes of Health (NIH) Grants P30
AG024824 (Alexander), P30 AG024827 (Studenski), K24 AG019675
(Alexander), K07 AG023641 (Studenski), and P20 CA103730 (Studenski), as
well as from the Office of Research and Development, Clinical Science
and Rehabilitation Research and Development programs of the Department
of Veterans Affairs. Supported in part by the Intramural Research
Program of the National Institute on Aging, NIH, Baltimore, Maryland.
For more information on the Bedside-to-Bench Conference on Idiopathic
Fatigue and Aging and to view presentations, visit
http://www.americangeriatrics.org/research/confseries/2008_ifa.shtml.;
Conference speakers: Neil Alexander, University of Michigan; Francisco
H. Andrade, University of Kentucky; Zeeshan Butt, Northwestern
University; Francesco S. Celi, National Institute of Diabetes and
Digestive and Kidney Diseases; Kong Chen, National Institute of Diabetes
and Digestive and Kidney Diseases; Charles Cleeland, University of Texas
MD Anderson Cancer Center; Robert Dantzer, University of Illinois at
Urbana-Champaign; Basil Eldadah, National Institute on Aging; Luigi
Ferrucci, National Institute on Aging; Mariana Gerschenson, University
of Hawaii at Manoa; Bret Goodpaster, University of Pittsburgh Medical
Center; Evan Hadley, National Institute on Aging; Jane Kent-Braun,
University of Massachusetts; Donna Mancini, Columbia University; Romain
Meeusen, Vrije Universiteit Brussel; George Taffet, Baylor College of
Medicine; Doug Wallace, University of California, Irvine; Phyllis Zee,
Northwestern University.; Conflict of Interest: The authors declare no
conflict of interest.; Author Contributions: All of the authors
contributed to the review, concept, design, and preparation of this
manuscript.; Sponsor's Role: The sponsors had no role in the design,
methods, or preparation of this manuscript.
NR 82
TC 43
Z9 43
U1 1
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2010
VL 58
IS 5
BP 967
EP 975
DI 10.1111/j.1532-5415.2010.02811.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 592XE
UT WOS:000277414400024
PM 20722821
ER
PT J
AU Aronson, AR
Lang, FM
AF Aronson, Alan R.
Lang, Francois-Michel
TI An overview of MetaMap: historical perspective and recent advances
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID MEDICAL TEXT INDEXER; RETRIEVAL; TERMS
AB MetaMap is a widely available program providing access to the concepts in the unified medical language system (UMLS) Metathesaurus from biomedical text. This study reports on MetaMap's evolution over more than a decade, concentrating on those features arising out of the research needs of the biomedical informatics community both within and outside of the National Library of Medicine. Such features include the detection of author-defined acronyms/abbreviations, the ability to browse the Metathesaurus for concepts even tenuously related to input text, the detection of negation in situations in which the polarity of predications is important, word sense disambiguation (WSD), and various technical and algorithmic features. Near-term plans for MetaMap development include the incorporation of chemical name recognition and enhanced WSD.
C1 [Aronson, Alan R.; Lang, Francois-Michel] NIH, LHNCBC, US Natl Lib Med, Bethesda, MD 20892 USA.
RP Aronson, AR (reprint author), Natl Lib Med, Bldg 38A,Room 9N-905,8600 Rockville Pike,MSC 3826, Bethesda, MD 20894 USA.
EM alan@nlm.nih.gov
FU National Institutes of Health; National Library of Medicine
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Library of Medicine.
NR 49
TC 279
Z9 282
U1 6
U2 42
PU HANLEY & BELFUS-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD MAY
PY 2010
VL 17
IS 3
BP 229
EP 236
DI 10.1136/jamia.2009.002733
PG 8
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 594ZP
UT WOS:000277580700001
PM 20442139
ER
PT J
AU Coudert, B
Ciuleanu, T
Park, K
Wu, Y
Giaccone, G
Cappuzzo, F
AF Coudert, B.
Ciuleanu, T.
Park, K.
Wu, Y.
Giaccone, G.
Cappuzzo, F.
TI SURVIVAL BENEFIT WITH ERLOTINIB MAINTENANCE THERAPY RELATIVE TO PRIOR
CHEMOTHERAPEUTIC RESPONSE: A SUBANALYSIS OF THE PHASE III SATURN STUDY
IN NSCLC
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Coudert, B.] Ctr Georges Francois Leclerc, Dijon, France.
[Ciuleanu, T.] Inst Oncol Prof Dr I Chiricuta, Cluj Napoca, Romania.
[Park, K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea.
[Wu, Y.] Lung Canc Res Inst, Guangzhou, Peoples R China.
[Wu, Y.] Ctr Canc, Dept Lung Canc, Guangzhou, Peoples R China.
[Giaccone, G.] NCI, Chief Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Cappuzzo, F.] Livorno Hosp, Livorno, Italy.
RI Ciuleanu, Tudor Eliade/C-3996-2011
NR 0
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD MAY
PY 2010
VL 5
IS 5
SU 1
BP S80
EP S80
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 590QU
UT WOS:000277242900200
ER
PT J
AU Hicks, RR
Fertig, SJ
Desrocher, RE
Koroshetz, WJ
Pancrazio, JJ
AF Hicks, Ramona R.
Fertig, Stephanie J.
Desrocher, Rebecca E.
Koroshetz, Walter J.
Pancrazio, Joseph J.
TI Neurological Effects of Blast Injury
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Review
DE Blast injury; Traumatic brain injury; Polytrauma; Detonation
ID TRAUMATIC BRAIN-INJURY; TYMPANIC-MEMBRANE PERFORATION;
CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; RAT-BRAIN; HEAD-INJURY;
INDUCED NEUROTRAUMA; TERRORIST BOMBINGS; IRAQ; EXPERIENCE
AB Over the last few years, thousands of soldiers and an even greater number of civilians have suffered traumatic injuries due to blast exposure, largely attributed to improvised explosive devices in terrorist and insurgent activities. The use of body armor is allowing soldiers to survive blasts that would otherwise be fatal due to systemic damage. Emerging evidence suggests that exposure to a blast can produce neurologic consequences in the brain but much remains unknown. To elucidate the current scientific basis for understanding blast-induced traumatic brain injury (bTBI), the NIH convened a workshop in April 2008. A multidisciplinary group of neuroscientists, engineers, and clinicians were invited to share insights on bTBI, specifically pertaining to: physics of blast explosions, acute clinical observations and treatments, preclinical and computational models, and lessons from the international community on civilian exposures. This report provides an overview of the state of scientific knowledge of bTBI, drawing from the published literature, as well as presentations, discussions, and recommendations from the workshop. One of the major recommendations from the workshop was the need to characterize the effects of blast exposure on clinical neuropathology. Clearer understanding of the human neuropathology would enable validation of preclinical and computational models, which are attempting to simulate blast wave interactions with the central nervous system. Furthermore, the civilian experience with bTBI suggests that polytrauma models incorporating both brain and lung injuries may be more relevant to the study of civilian countermeasures than considering models with a neurologic focus alone.
C1 [Hicks, Ramona R.; Fertig, Stephanie J.; Desrocher, Rebecca E.; Koroshetz, Walter J.; Pancrazio, Joseph J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Hicks, RR (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, NSC 2206,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM hicksra@ninds.nih.gov
RI Pancrazio, Joseph/M-3206-2015
OI Pancrazio, Joseph/0000-0001-8276-3690
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health; Defense and Veterans Brain Injury Center; Office
of Research and Development, Department of Veterans Affairs; Interagency
Committee on Disability Research
FX Supported by National Institute of Neurological Disorders and Stroke,
National Institutes of Health; Defense and Veterans Brain Injury Center;
Office of Research and Development, Department of Veterans Affairs;
Interagency Committee on Disability Research.
NR 69
TC 50
Z9 55
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD MAY
PY 2010
VL 68
IS 5
BP 1257
EP 1263
DI 10.1097/TA.0b013e3181d8956d
PG 7
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 595MQ
UT WOS:000277615200036
PM 20453776
ER
PT J
AU Liu, NW
Khurana, K
Sudarshan, S
Pinto, PA
Linehan, WM
Bratslaysky, G
AF Liu, Nick W.
Khurana, Kiranpreet
Sudarshan, Sunil
Pinto, Peter A.
Linehan, W. Marston
Bratslaysky, Gennady
TI Repeat Partial Nephrectomy on the Solitary Kidney: Surgical, Functional
and Oncological Outcomes
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; carcinoma, renal cell; nephrectomy; treatment outcome; von
Hippel-Lindau disease
ID RESIDUAL RENAL-FUNCTION; PERITONEAL-DIALYSIS PATIENTS; NEPHRON-SPARING
SURGERY; HIPPEL-LINDAU-DISEASE; CELL CARCINOMA; RADICAL NEPHRECTOMY;
NATURAL-HISTORY; REMOVAL; MASSES; TUMOR
AB Purpose: We examined outcomes in patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney.
Materials and Methods: We reviewed the records of patients who underwent nephron sparing surgery at the National Cancer Institute from 1989 to 2008. Patients were included in analysis if they underwent repeat partial nephrectomy on a solitary kidney. Perioperative, functional and oncological outcomes were assessed. Functional outcomes were evaluated using the Modification of Diet in Renal Disease equation for the estimated glomerular filtration rate. Oncological efficacy was examined by the need for subsequent repeat renal surgery and the development of metastatic disease.
Results: A total of 25 patients were included in the analysis. A median of 4 tumors were resected. Median estimated blood loss was 2,400 ml and median operative time was 8.5 hours. Perioperative complications occurred in 52% of patients, including 1 death and the loss of 3 renal units. There was a decrease in the estimated glomerular filtration rate at followup visit 1 within 3 months after surgery but at 1-year followup the difference was not significant (p < 0.01 and 0.12, respectively). Surgical intervention was recommended in 8 patients (38%) for recurrent or de novo tumors at a median of 36 months. The average metastasis-free survival rate in the cohort was 95% at 57 months (median 50, range 3 to 196).
Conclusions: Repeat partial nephrectomy in patients with solitary kidney is a high risk alternative. The complication rate is high and there is a modest decrease in renal function but most patients remain free of dialysis with acceptable oncological outcomes at intermediate followup.
C1 [Bratslaysky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Sudarshan, Sunil] San Antonio Med Ctr Hosp, Dept Urol, San Antonio, TX USA.
RP Bratslaysky, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
OI Khurana, Kiranpreet/0000-0002-2750-4909
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Supported by the National Institutes of Health, National Cancer
Institute, Center for Cancer Research Intramural Research Program.
NR 30
TC 21
Z9 22
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAY
PY 2010
VL 183
IS 5
BP 1719
EP 1724
DI 10.1016/j.juro.2010.01.010
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 584JJ
UT WOS:000276747600016
PM 20299057
ER
PT J
AU Berry, SH
Bogart, LM
Pham, C
Liu, K
Nyberg, L
Stoto, M
Suttorp, M
Clemens, JQ
AF Berry, Sandra H.
Bogart, Laura M.
Pham, Chau
Liu, Karin
Nyberg, Leroy
Stoto, Michael
Suttorp, Marika
Clemens, J. Quentin
TI Development, Validation and Testing of an Epidemiological Case
Definition of Interstitial Cystitis/Painful Bladder Syndrome
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary bladder; cystitis, interstitial; pain; epidemiology; diagnosis
ID QUALITY-OF-LIFE; CORONARY REVASCULARIZATION; OVERACTIVE BLADDER;
APPROPRIATENESS; SYMPTOMS; PREVALENCE; POPULATION; WOMEN; PANEL;
UNDERUSE
AB Purpose: No standard case definition exists for interstitial cystitis/painful bladder syndrome for patient screening or epidemiological studies. As part of the RAND Interstitial Cystitis Epidemiology study, we developed a case definition for interstitial cystitis/painful bladder syndrome with known sensitivity and specificity. We compared this definition with others used in interstitial cystitis/painful bladder syndrome epidemiological studies.
Materials and Methods: We reviewed the literature and performed a structured, expert panel process to arrive at an interstitial cystitis/painful bladder syndrome case definition. We developed a questionnaire to assess interstitial cystitis/painful bladder syndrome symptoms using this case definition and others used in the literature. We administered the questionnaire to 599 women with interstitial cystitis/painful bladder syndrome, overactive bladder, endometriosis or vulvodynia. The sensitivity and specificity of each definition was calculated using physician assigned diagnoses as the reference standard.
Results: No single epidemiological definition had high sensitivity and high specificity. Thus, 2 definitions were developed. One had high sensitivity (81%) and low specificity (54%), and the other had the converse (48% sensitivity and 83% specificity). These values were comparable or superior to those of other epidemiological definitions used in interstitial cystitis/painful bladder syndrome prevalence studies.
Conclusions: No single case definition of interstitial cystitis/painful bladder syndrome provides high sensitivity and high specificity to identify the condition. For prevalence studies of interstitial cystitis/painful bladder syndrome the best approach may be to use 2 definitions that would yield a prevalence range. The RAND Interstitial Cystitis Epidemiology interstitial cystitis/painful bladder syndrome case definitions, developed through structured consensus and validation, can be used for this purpose.
C1 [Berry, Sandra H.; Pham, Chau; Liu, Karin; Stoto, Michael] RAND Corp, Santa Monica, CA 90407 USA.
[Bogart, Laura M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Nyberg, Leroy] NIDDKD, Bethesda, MD 20892 USA.
[Suttorp, Marika] Georgetown Univ, Washington, DC USA.
[Clemens, J. Quentin] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
RP Berry, SH (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA.
EM berry@rand.org
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U10DK070234-01]
FX Supported by National Institute of Diabetes and Digestive and Kidney
Diseases Grant U10DK070234-01.
NR 24
TC 38
Z9 38
U1 0
U2 1
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 MAY
PY 2010
VL 183
IS 5
BP 1848
EP 1852
DI 10.1016/j.juro.2009.12.103
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 584JJ
UT WOS:000276747600067
PM 20303099
ER
PT J
AU Foster, HE
Hanno, PM
Nickel, JC
Payne, CK
Mayer, RD
Burks, DA
Yang, CC
Chai, TC
Kreder, KJ
Peters, KM
Lukacz, ES
FitzGerald, MP
Cen, LY
Landis, JR
Propert, KJ
Yang, W
Kusek, JW
Nyberg, LM
AF Foster, Harris E., Jr.
Hanno, Philip M.
Nickel, J. Curtis
Payne, Christopher K.
Mayer, Robert D.
Burks, David A.
Yang, Claire C.
Chai, Toby C.
Kreder, Karl J.
Peters, Kenneth M.
Lukacz, Emily S.
FitzGerald, Mary P.
Cen, Liyi
Landis, J. Richard
Propert, Kathleen J.
Yang, Wei
Kusek, John W.
Nyberg, Leroy M.
CA Interstitial Cystitis Collaborativ
TI Effect of Amitriptyline on Symptoms in Treatment Naive Patients With
Interstitial Cystitis/Painful Bladder Syndrome
SO JOURNAL OF UROLOGY
LA English
DT Article
DE cystitis, interstitial; amitriptyline; patient education as topic
ID URINARY-INCONTINENCE; SCALE; INDEX; MANAGEMENT; URGENCY; FEMALE; WOMEN
AB Purpose: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports.
Materials and Methods: We conducted a multicenter, randomized,double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naive to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment.
Results: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01).
Conclusions: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.
C1 [Foster, Harris E., Jr.] Yale Univ, Sch Med, Dept Surg, Urol Sect, New Haven, CT 06520 USA.
[Hanno, Philip M.] Univ Penn, Div Urol, Philadelphia, PA 19104 USA.
[Cen, Liyi; Landis, J. Richard; Propert, Kathleen J.; Yang, Wei] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Nickel, J. Curtis] Queens Univ, Dept Urol, Kingston, ON, Canada.
[Payne, Christopher K.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA.
[Lukacz, Emily S.] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA.
[Mayer, Robert D.] Univ Rochester, Dept Urol, Rochester, NY USA.
[Burks, David A.] Henry Ford Hosp, Dept Urol, Detroit, MI 48202 USA.
[Peters, Kenneth M.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Yang, Claire C.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Chai, Toby C.] Univ Maryland, Div Urol, Baltimore, MD 21201 USA.
[Kusek, John W.; Nyberg, Leroy M.] NIDDKD, Bethesda, MD 20892 USA.
[Kreder, Karl J.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA.
[FitzGerald, Mary P.] Loyola Univ, Dept Obstet & Gynecol, Maywood, IL 60153 USA.
[FitzGerald, Mary P.] Loyola Univ, Dept Urol, Maywood, IL 60153 USA.
RP Foster, HE (reprint author), Yale Univ, Sch Med, Dept Surg, Urol Sect, POB 208041,800 Howard Ave,YPB318, New Haven, CT 06520 USA.
EM harris.foster@yale.edu
RI Yang, Wei/A-9223-2009;
OI Yang, Wei/0000-0001-8984-4389; Landis, J Richard/0000-0001-8099-0988
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK65209, 5U01 DK65255-06, U01 DK65271, U01 DK65213, U01 DK65214, U01
DK65215, U01 DK65178, U01 DK65190, U01 DK65192, U01 DK65255, U01
DK65267, 5U01 DK65202]
FX Supported by cooperative agreements U01 DK65209, 5U01 DK65255-06. U01
DK65271, U01 DK65213, U01 DK65214, U01 DK65215, U01 DK65178, U01
DK65190, U01 DK65192, U01 DK65255, U01 DK65267, U01 DK65271, 5U01
DK65202 from the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 25
TC 52
Z9 53
U1 0
U2 1
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 MAY
PY 2010
VL 183
IS 5
BP 1853
EP 1858
DI 10.1016/j.juro.2009.12.106
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 584JJ
UT WOS:000276747600068
PM 20303115
ER
PT J
AU Siber, A
Rajter, RF
French, RH
Ching, WY
Parsegian, VA
Podgornik, R
AF Siber, A.
Rajter, R. F.
French, R. H.
Ching, W. Y.
Parsegian, V. A.
Podgornik, R.
TI Optically anisotropic infinite cylinder above an optically anisotropic
half space: Dispersion interaction of a single-walled carbon nanotube
with a substrate
SO JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B
LA English
DT Article
DE ab initio calculations; carbon nanotubes; disperse systems;
semiconductor nanotubes; semiconductor-insulator boundaries; van der
Waals forces
AB A complete form of the van der Waals dispersion interaction between an infinitely long anisotropic semiconducting/insulating thin cylinder and an anisotropic half space is derived for all separations between the cylinder and the half space. The derivation proceeds from the theory of dispersion interactions between two anisotropic infinite half spaces as formulated in Phys. Rev. A 71, 042102 (2005). The approach is valid in the retarded as well as nonretarded regimes of the interaction and is coupled with the recently evaluated ab initio dielectric response functions of various semiconducting/insulating single wall carbon nanotubes, enables the authors to evaluate the strength of the van der Waals dispersion interaction for all orientation angles and separations between a thin cylindrical nanotube and the half space. The possibility of repulsive and/or nonmonotonic dispersion interactions is examined in detail. (C) 2010 American Vacuum Society. [DOI: 10.1116/1.3416904]
C1 [Siber, A.] Inst Phys, Zagreb 10001, Croatia.
[Rajter, R. F.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
[French, R. H.] DuPont Co Inc, Cent Res, Wilmington, DE 19880 USA.
[Ching, W. Y.] Univ Missouri, Dept Phys, Kansas City, MO 64110 USA.
[Parsegian, V. A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Podgornik, R.] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA.
[Podgornik, R.] Univ Ljubljana, Dept Phys, Fac Math & Phys, SI-1000 Ljubljana, Slovenia.
[Podgornik, R.] Univ Ljubljana, Sch Med, Inst Biophys, SI-1000 Ljubljana, Slovenia.
[Podgornik, R.] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia.
RP Siber, A (reprint author), Inst Phys, Bijenicka Cesta 46,POB 304, Zagreb 10001, Croatia.
EM podgornr@mail.nih.gov
RI Ching, Wai-Yim/B-4686-2009; Siber, Antonio/B-8881-2008; French,
Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008
OI Ching, Wai-Yim/0000-0001-7738-8822; Siber, Antonio/0000-0003-1665-6541;
French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637
NR 16
TC 4
Z9 4
U1 1
U2 7
PU A V S AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 1071-1023
J9 J VAC SCI TECHNOL B
JI J. Vac. Sci. Technol. B
PD MAY
PY 2010
VL 28
IS 3
DI 10.1116/1.3416904
PG 8
WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology;
Physics, Applied
SC Engineering; Science & Technology - Other Topics; Physics
GA 603BK
UT WOS:000278182700090
ER
PT J
AU Tsihlis, ND
Murar, J
Kapadia, MR
Ahanchi, SS
Oustwani, CS
Saavedra, JE
Keefer, LK
Kibbe, MR
AF Tsihlis, Nick D.
Murar, Jozef
Kapadia, Muneera R.
Ahanchi, Sadaf S.
Oustwani, Christopher S.
Saavedra, Joseph E.
Keefer, Larry K.
Kibbe, Melina R.
TI Isopropylamine NONOate (IPA/NO) moderates neointimal hyperplasia
following vascular injury
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; BARE-METAL STENTS; NITRIC-OXIDE; IN-VIVO;
GUANOSINE-MONOPHOSPHATE; S-NITROSOTHIOLS; ELUTING STENTS; GENE-TRANSFER;
NITROXYL HNO; NO DONOR
AB Objective: Isopropylamine NONOate (IPA/NO) is a nitroxyl (HNO) donor at physiologic pH. HNO is a positive inotrope and vasodilator, but little is known about its effect on neointimal hyperplasia. The aims of this study are to determine the effect of IPA/NO on endothelial and vascular smooth muscle cells (VSMC) in vitro and to determine if IPA/NO inhibits neointimal hyperplasia in vivo.
Methods: VSMC were harvested from the abdominal aortas of male Sprague Dawley rats, and human umbilical vein endothelial cells were purchased from ATCC. In vitro, cellular proliferation was assessed by (3)H-thymidine incorporation, cell migration was assessed using the scrape assay, and cell death was assessed using Guava personal cell analysis (PCA). Cell cycle analysis was performed using propidium iodide staining and flow cytometry analysis. Protein expression was assessed using Western blot analysis. Phosphorylated proteins were assessed using immunoprecipitation and Western blot analysis. In vivo, the carotid artery injury model was performed on male Sprague Dawley rats treated with (n = 12) or without (n = 6) periadventitial IPA/NO (10 mg). Arteries harvested at 2 weeks were assessed for morphometrics using ImageJ. Inflammation was assessed using immunohistochemistry. Endothelialization was assessed by Evans blue staining of carotid arteries harvested 7 days after balloon injury from rats treated with (n = 6) or without (n = 3) periadventitial IPA/NO (10 mg).
Results: In vitro, 1000 mu mol/L IPA/NO inhibited both VSMC (38.7 +/- 4.5% inhibition vs control, P = .003) and endothelial cell proliferation (54.0 +/- 2.9% inhibition vs control, P <= 0.001) without inducing cell death or inhibiting migration. In VSMC, this inhibition was associated with an S-phase cell cycle arrest and increased expression of cyclin A, cyclin D1, and the cyclin-dependent kinase inhibitor p21. No change was noted in the phosphorylation status of cdk2, cdk4, or cdk6 by IPA/NO. In rodents subjected to the carotid artery balloon injury model, IPA/NO caused significant reductions in neointimal area (298 +/- 20 vs 422 +/- 30, P <= .001) and medial area (311 +/- 14 vs 449 +/- 16, P <= .001) compared with injury alone, and reduced macrophage infiltration to 1.7 +/- 0.8 from 16.1 +/- 3.5 cells per high power field (P <= .001). IPA/NO also prevented re-endothelialization compared with injury alone (55.9 +/- 0.5% nonendothelialized vs 21 +/- 4.4%, respectively, P = .001). Lastly, a 50% mortality rate was observed in the IPA/NO-treated groups.
Conclusions: In summary, while IPA/NO modestly inhibited neointimal hyperplasia by inhibiting VSMC proliferation and macrophage infiltration, it also inhibited endothelial cell proliferation and induced significant mortality in our animal model. Since HNO is being investigated as a treatment for congestive heart failure, our results raise some concerns about the use of IPA/NO in the vasculature and suggest that further studies be conducted on the safety of HNO donors in the cardiovascular system. (J Vasc Surg 2010;51:1248-59.)
C1 [Tsihlis, Nick D.; Murar, Jozef; Kapadia, Muneera R.; Oustwani, Christopher S.; Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA.
[Tsihlis, Nick D.; Murar, Jozef; Kapadia, Muneera R.; Oustwani, Christopher S.; Kibbe, Melina R.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA.
[Ahanchi, Sadaf S.] Univ Illinois Mt Sinai, Dept Surg, Chicago, IL USA.
[Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
[Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA.
RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, 676 N St Clair,650, Chicago, IL 60611 USA.
EM mkibbe@nmh.org
RI Keefer, Larry/N-3247-2014;
OI Keefer, Larry/0000-0001-7489-9555; Tsihlis, Nick/0000-0002-0410-0143
FU National Institutes of Health [1K08HL084203]; American Vascular
Association; Department of Veterans Affairs; National Cancer Institute,
National Institutes of Health [NO1-CO-12400]; NIH, National Cancer
Institute, Center for Cancer Research
FX This work was supported by the National Institutes of Health
(1K08HL084203 to M.R.K.), the American Vascular Association (to M.R.K.),
Department of Veterans Affairs (Merit Review Grant to M.R.K.), Mrs Hilda
Rosenbloom (to M.R.K.), Ms Eleanor Baldwin (to M.R.K.), the National
Cancer Institute, National Institutes of Health with SAIC-Frederick, Inc
(Contract NO1-CO-12400 to J.E.S.), and the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research (to
L.K.K.).
NR 37
TC 20
Z9 20
U1 3
U2 11
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAY
PY 2010
VL 51
IS 5
BP 1248
EP 1259
DI 10.1016/j.jvs.2009.12.028
PG 12
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 590HL
UT WOS:000277216000027
PM 20223627
ER
PT J
AU Schwartz, JA
Buonocore, L
Suguitan, AL
Silaghi, A
Kobasa, D
Kobinger, G
Feldmann, H
Subbarao, K
Rose, JK
AF Schwartz, Jennifer A.
Buonocore, Linda
Suguitan, Amorsolo L., Jr.
Silaghi, Alex
Kobasa, Darwyn
Kobinger, Gary
Feldmann, Heinz
Subbarao, Kanta
Rose, John K.
TI Potent Vesicular Stomatitis Virus-Based Avian Influenza Vaccines Provide
Long-Term Sterilizing Immunity against Heterologous Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; H5N1 VACCINE; NEUTRALIZING ANTIBODIES;
REPLICATION-COMPETENT; NONHUMAN-PRIMATES; CROSS-PROTECTION; VECTORS;
MICE; IMMUNIZATION; INFECTION
AB The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine expressing H5 hemagglutinin (HA) from the fifth genomic position of VSV (J. A. Schwartz et al., Virology 366: 166-173, 2007). Here we have generated and characterized VSV-based vaccines that express the A/Hong Kong/156/1997 (clade 0) H5 HA from the first position of the VSV genome. These vectors induce broadly cross-neutralizing antibodies against homologous and heterologous H5N1 viruses of different clades in mice. The vaccines provide complete protection against morbidity and mortality after heterologous challenge with clade 0 and clade 1 strains in animals even 1 year after vaccination. Postchallenge pulmonary virus loads show that these vectors provide sterilizing immunity. Therefore, VSV-based AIV vaccines are potent, broadly cross-protective pandemic vaccine candidates.
C1 [Schwartz, Jennifer A.; Buonocore, Linda; Rose, John K.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Suguitan, Amorsolo L., Jr.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Silaghi, Alex; Kobasa, Darwyn; Kobinger, Gary; Feldmann, Heinz] Canadian Sci Ctr Human & Anim Hlth, Natl Microbiol Lab, Winnipeg, MB, Canada.
RP Rose, JK (reprint author), Yale Univ, Sch Med, Dept Pathol, 310 Cedar St,LH 315, New Haven, CT 06520 USA.
EM john.rose@yale.edu
OI Schwartz, Jennifer/0000-0001-8239-8857
FU NIH [RO1 AI080781, U54 AI057158]; NIH; NIAID; Public Health Agency of
Canada; Canadian Institute for Health Research [166339, 310641]
FX This work was funded in part by the following: NIH grants RO1 AI080781
and U54 AI057158; the Intramural Research Program of the NIH, NIAID; the
Public Health Agency of Canada; and grants 166339 and 310641 from the
Canadian Institute for Health Research.
NR 42
TC 27
Z9 28
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 MAY
PY 2010
VL 84
IS 9
BP 4611
EP 4618
DI 10.1128/JVI.02637-09
PG 8
WC Virology
SC Virology
GA 579GW
UT WOS:000276358000046
PM 20181720
ER
PT J
AU Habermann, A
Krijnse-Locker, J
Oberwinkler, H
Eckhardt, M
Homann, S
Andrew, A
Strebel, K
Krausslich, HG
AF Habermann, Anja
Krijnse-Locker, Jacomine
Oberwinkler, Heike
Eckhardt, Manon
Homann, Stefanie
Andrew, Amy
Strebel, Klaus
Kraeusslich, Hans-Georg
TI CD317/Tetherin Is Enriched in the HIV-1 Envelope and Downregulated from
the Plasma Membrane upon Virus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; CELL-SURFACE; RESTRICTION FACTOR; VPU
PROTEIN; RELEASE; TYPE-1; RAFT; BST-2/TETHERIN; DEGRADATION; RECEPTORS
AB CD317/Bst-2/tetherin is a host factor that restricts the release of human immunodeficiency virus type 1 (HIV-1) by trapping virions at the plasma membrane of certain producer cells. It is antagonized by the HIV-1 accessory protein Vpu. Previous light microscopy studies localized CD317 to the plasma membrane and the endosomal compartment and showed Vpu induced downregulation. In the present study, we performed quantitative immunoelectron microscopy of CD317 in cells producing wild-type or Vpu-defective HIV-1 and in control cells. Double-labeling experiments revealed that CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network. CD317 largely relocated to endosomes upon HIV-1 infection, and this effect was partly counteracted by Vpu. Unexpectedly, CD317 was enriched in the membrane of viral buds and cell-associated and cell-free viruses compared to the respective plasma membrane, and this enrichment was independent of Vpu. These results suggest that the tethering activity of CD317 critically depends on its density at the cell surface and appears to be less affected by its density in the virion membrane.
C1 [Habermann, Anja; Krijnse-Locker, Jacomine; Oberwinkler, Heike; Eckhardt, Manon; Homann, Stefanie; Kraeusslich, Hans-Georg] Univ Heidelberg, Dept Infect Dis, D-69120 Heidelberg, Germany.
[Krijnse-Locker, Jacomine] Univ Heidelberg, Electron Microscopy Core Facil, D-69120 Heidelberg, Germany.
[Andrew, Amy; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Krausslich, HG (reprint author), Univ Heidelberg, Dept Infect Dis, Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
EM hans-georg.kraeusslich@med.uni-heidelberg.de
FU Deutsche Forschungsgemeinschaft [SFB638, A9]; EU
FX This study was supported in part by grants from the Deutsche
Forschungsgemeinschaft (SFB638, A9) and within the EU FP7 program
(HIV-ACE). H.-G. K. is an investigator in the CellNetworks Cluster of
Excellence (ECX81).
NR 33
TC 62
Z9 65
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 MAY
PY 2010
VL 84
IS 9
BP 4646
EP 4658
DI 10.1128/JVI.02421-09
PG 13
WC Virology
SC Virology
GA 579GW
UT WOS:000276358000049
PM 20147389
ER
PT J
AU Easley, R
Carpio, L
Guendel, I
Klase, Z
Choi, SY
Kehn-Hall, K
Brady, JN
Kashanchi, F
AF Easley, Rebecca
Carpio, Lawrence
Guendel, Irene
Klase, Zachary
Choi, Soyun
Kehn-Hall, Kylene
Brady, John N.
Kashanchi, Fatah
TI Human T-Lymphotropic Virus Type 1 Transcription and Chromatin-Remodeling
Complexes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CREB-BINDING-PROTEIN; CELL-CYCLE ARREST; I TAX; SWI/SNF COMPLEX; C-MYB;
HISTONE ACETYLTRANSFERASE; NUCLEAR RECEPTOR; COACTIVATOR CBP;
GENE-EXPRESSION; ACTIVATION
AB Human T-lymphotropic virus type 1 (HTLV-1) encodes the viral protein Tax, which is believed to act as a viral transactivator through its interactions with a variety of transcription factors, including CREB and NF-kappa B. As is the case for all retroviruses, the provirus is inserted into the host DNA, where nucleosomes are deposited to ensure efficient packaging. Nucleosomes act as roadblocks in transcription, making it difficult for RNA polymerase II (Pol II) to proceed toward the 3 ' end of the genome. Because of this, a variety of chromatin remodelers can act to modify nucleosomes, allowing for efficient transcription. While a number of covalent modifications are known to occur on histone tails in HTLV-1 infection (i.e., histone acetyltransferases [HATs], histone deacetylases [HDACs], and histone methyltransferases [HMTs]), evidence points to the use of chromatin remodelers that use energy from ATP hydrolysis to remodel nucleosomes. Here we confirm that BRG1, which is the core subunit of eight chromatin-remodeling complexes, is essential not only for Tax transactivation but also for viral replication. This is especially evident when wild-type infectious clones of HTLV-1 are used. BRG1 associates with Tax at the HTLV-1 long terminal repeat (LTR), and coexpression of BRG1 and Tax results in increased rates of transcription. The interaction of BRG1 with Tax additionally recruits the basal transcriptional machinery and removes some of the core histones from the nucleosome at the start site (Nuc 1). When using the BRG1-deficient cell lines SW13, C33A, and TSUPR1, we observed little viral transcription and no viral replication. Importantly, while these three cell lines do not express detectable levels of BRG1, much of the SWI/SNF complex remains assembled in the cells. Knockdown of BRG1 and associated SWI/SNF subunits suggests that the BRG1-utilizing SWI/SNF complex PBAF is responsible for HTLV-1 nucleosome remodeling. Finally, HTLV-1 infection of cell lines with a knockdown in BRG1 or the PBAF complex results in a significant reduction in viral production. Overall, we concluded that BRG1 is required for Tax transactivation and HTLV-1 viral production and that the PBAF complex appears to be responsible for nucleosome remodeling.
C1 [Easley, Rebecca; Carpio, Lawrence; Guendel, Irene; Choi, Soyun; Kashanchi, Fatah] George Washington Univ, Sch Med, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
[Klase, Zachary] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Brady, John N.] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kehn-Hall, Kylene] George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Manassas, VA USA.
RP Kashanchi, F (reprint author), George Washington Univ, Sch Med, Dept Microbiol Immunol & Trop Med, 2300 1 St NW,Ross Hall,Room 551, Washington, DC 20037 USA.
EM bcmfxk@gwumc.edu
RI Kehn-Hall, Kylene/I-5752-2013
FU George Washington University; NIH [AI44357, AI43894, AI46459]
FX This work was supported by grants from the George Washington University
(REF funds to F. K. and Akos Vertes) and by NIH grants AI44357, AI43894,
and AI46459 to F. K.
NR 76
TC 15
Z9 17
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 MAY
PY 2010
VL 84
IS 9
BP 4755
EP 4768
DI 10.1128/JVI.00851-09
PG 14
WC Virology
SC Virology
GA 579GW
UT WOS:000276358000059
PM 20164218
ER
PT J
AU Nishimura, Y
Shingai, M
Willey, R
Sadjadpour, R
Lee, WR
Brown, CR
Brenchley, JM
Buckler-White, A
Petros, R
Eckhaus, M
Hoffman, V
Igarashi, T
Martin, MA
AF Nishimura, Yoshiaki
Shingai, Masashi
Willey, Ronald
Sadjadpour, Reza
Lee, Wendy R.
Brown, Charles R.
Brenchley, Jason M.
Buckler-White, Alicia
Petros, Rahel
Eckhaus, Michael
Hoffman, Victoria
Igarashi, Tatsuhiko
Martin, Malcolm A.
TI Generation of the Pathogenic R5-Tropic Simian/Human Immunodeficiency
Virus SHIVAD8 by Serial Passaging in Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; BLOOD MONONUCLEAR-CELLS; PIG-TAILED MACAQUES;
GASTROINTESTINAL-TRACT; CORECEPTOR SWITCH; PERSISTENT INFECTION;
CLINICAL-OUTCOMES; HIV-1 INFECTION; TYPE-1 HIV-1; AIDS
AB A new pathogenic R5-tropic simian/human immunodeficiency virus (SHIV) was generated following serial passaging in rhesus macaques. All 13 animals inoculated with SHIVAD8 passaged lineages experienced marked depletions of CD4(+) T cells. Ten of these infected monkeys became normal progressors (NPs) and had gradual losses of both memory and naive CD4(+) T lymphocytes, generated antiviral CD4(+) and CD8(+) T cell responses, and sustained chronic immune activation while maintaining variable levels of plasma viremia (10(2) to 10(5) RNA copies/ml for up to 3 years postinfection [p.i.]). To date, five NPs developed AIDS associated with opportunistic infections caused by Pneumocystis carinii, Mycobacterium avium, and Campylobacter coli that required euthanasia between weeks 100 and 199 p.i. Three other NPs have experienced marked depletions of circulating CD4(+) T lymphocytes (92 to 154 cells/mu l) following 1 to 2 years of infection. When tested for coreceptor usage, the viruses isolated from four NPs at the time of their euthanasia remained R5 tropic. Three of the 13 SHIVAD8-inoculated macaques experienced a rapid-progressor syndrome characterized by sustained plasma viremia of >1 x 107 RNA copies/ml and rapid irreversible loss of memory CD4(+) T cells that required euthanasia between weeks 19 and 23 postinfection. The sustained viremia, associated depletion of CD4(+) T lymphocytes, and induction of AIDS make the SHIVAD8 lineage of viruses a potentially valuable reagent for vaccine studies.
C1 [Nishimura, Yoshiaki; Shingai, Masashi; Willey, Ronald; Sadjadpour, Reza; Lee, Wendy R.; Brown, Charles R.; Brenchley, Jason M.; Buckler-White, Alicia; Igarashi, Tatsuhiko; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Petros, Rahel] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Eckhaus, Michael; Hoffman, Victoria] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Off Director, Bethesda, MD 20892 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 315A,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM malm@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 53
TC 38
Z9 38
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2010
VL 84
IS 9
BP 4769
EP 4781
DI 10.1128/JVI.02279-09
PG 13
WC Virology
SC Virology
GA 579GW
UT WOS:000276358000060
PM 20147396
ER
PT J
AU Freel, SA
Lamoreaux, L
Chattopadhyay, PK
Saunders, K
Zarkowsky, D
Overman, RG
Ochsenbauer, C
Edmonds, TG
Kappes, JC
Cunningham, CK
Denny, TN
Weinhold, KJ
Ferrari, G
Haynes, BF
Koup, RA
Graham, BS
Roederer, M
Tomaras, GD
AF Freel, Stephanie A.
Lamoreaux, Laurie
Chattopadhyay, Pratip K.
Saunders, Kevin
Zarkowsky, David
Overman, R. Glenn
Ochsenbauer, Christina
Edmonds, Tara G.
Kappes, John C.
Cunningham, Coleen K.
Denny, Thomas N.
Weinhold, Kent J.
Ferrari, Guido
Haynes, Barton F.
Koup, Richard A.
Graham, Barney S.
Roederer, Mario
Tomaras, Georgia D.
TI Phenotypic and Functional Profile of HIV-Inhibitory CD8 T Cells Elicited
by Natural Infection and Heterologous Prime/Boost Vaccination
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SUPPRESSIVE ACTIVITY; TYPE-1 INFECTION; VIRUS; REPLICATION; VIREMIA;
LYMPHOCYTES; IDENTIFICATION; ASSOCIATION; MECHANISMS; RESPONSES
AB Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8(+) T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8(+) T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8(+) T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8(+) T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8(+) T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1 beta (MIP-1 beta) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8(+) T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8(+) T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.
C1 [Tomaras, Georgia D.] Duke Univ, Med Ctr, MSRBII, Human Vaccine Inst, Durham, NC 27710 USA.
[Freel, Stephanie A.; Saunders, Kevin; Overman, R. Glenn; Weinhold, Kent J.; Ferrari, Guido; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Weinhold, Kent J.; Haynes, Barton F.; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
[Saunders, Kevin; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Cunningham, Coleen K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Denny, Thomas N.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Lamoreaux, Laurie; Zarkowsky, David; Koup, Richard A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA.
[Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Ochsenbauer, Christina; Kappes, John C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Edmonds, Tara G.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
RP Tomaras, GD (reprint author), Duke Univ, Med Ctr, MSRBII, Human Vaccine Inst, Room 4079,106 Res Dr,Lasalle St Extens, Durham, NC 27710 USA.
EM roederer@nih.gov; gdt@duke.edu
RI Chattopadhyay, Pratip/B-9227-2008; Ferrari, Guido/A-6088-2015; Tomaras,
Georgia/J-5041-2016;
OI Denny, Thomas/0000-0002-7364-8276; Chattopadhyay,
Pratip/0000-0002-5457-9666
FU National Institutes of Health (NIH/NIAID/DAIDS) [RO1A5779]; CHAVI
[AI067854-05]; Duke University Center [P30 AI 64518]; UAB Center [P30
AI27767]
FX This work was supported by the National Institutes of Health
(NIH/NIAID/DAIDS) through RO1A5779 (G. D. T.) and CHAVI AI067854-05 (G.
D. T., J.C.K., and B. F. H.); the Molecular Virology and Clinical Cores
of the Duke University Center for AIDS Research P30 AI 64518 (G. D. T.,
C. K. C., and K.J.W.); the Nucleotide Sequencing and Virology Cores of
the UAB Center for AIDS Research P30 AI27767 (J.C.K.); and the
Intramural Research Program of the NIAID, NIH.
NR 26
TC 73
Z9 74
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 MAY
PY 2010
VL 84
IS 10
BP 4998
EP 5006
DI 10.1128/JVI.00138-10
PG 9
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600013
PM 20200250
ER
PT J
AU Walker, RC
Khan, MA
Kao, S
Goila-Gaur, R
Miyagi, E
Strebel, K
AF Walker, Robert C., Jr.
Khan, Mohammad A.
Kao, Sandra
Goila-Gaur, Ritu
Miyagi, Eri
Strebel, Klaus
TI Identification of Dominant Negative Human Immunodeficiency Virus Type 1
Vif Mutants That Interfere with the Functional Inactivation of APOBEC3G
by Virus-Encoded Vif
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID E3 UBIQUITIN LIGASE; HIV-1 REVERSE TRANSCRIPTION; ANTIVIRAL ACTIVITY;
VIRAL INFECTIVITY; ZINC-BINDING; SOCS-BOX; I VIF; VIRION INCORPORATION;
DEAMINASE APOBEC3G; ENZYME APOBEC3G
AB APOBEC3G (A3G) is a host cytidine deaminase that serves as a potent intrinsic inhibitor of retroviral replication. A3G is packaged into human immunodeficiency virus type 1 virions and deaminates deoxycytidine to deoxyuridine on nascent minus-strand retroviral cDNA, leading to hyper-deoxyguanine-to-deoxyadenine mutations on positive-strand cDNA and inhibition of viral replication. The antiviral activity of A3G is suppressed by Vif, a lentiviral accessory protein that prevents encapsidation of A3G. In this study, we identified dominant negative mutants of Vif that interfered with the ability of wild-type Vif to inhibit the encapsidation and antiviral activity of A3G. These mutants were nonfunctional due to mutations in the highly conserved HCCH and/or SOCS box motifs, which are required for assembly of a functional Cul5-E3 ubiquitin ligase complex. Similarly, mutation or deletion of a PPLP motif, which was previously reported to be important for Vif dimerization, induced a dominant negative phenotype. Expression of dominant negative Vif counteracted the Vif-induced reduction of intracellular A3G levels, presumably by preventing Vif-induced A3G degradation. Consequently, dominant negative Vif interfered with wild-type Vif's ability to exclude A3G from viral particles and reduced viral infectivity despite the presence of wild-type Vif. The identification of dominant negative mutants of Vif presents exciting possibilities for the design of novel antiviral strategies.
C1 [Walker, Robert C., Jr.; Khan, Mohammad A.; Kao, Sandra; Goila-Gaur, Ritu; Miyagi, Eri; Strebel, Klaus] NIAID, Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA.
RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
FU NIH; NIAID
FX This work was supported in part by a grant from the NIH Intramural AIDS
Targeted Antiviral Program to K.S. and by the Intramural Research
Program of the NIH, NIAID.
NR 78
TC 23
Z9 25
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 MAY
PY 2010
VL 84
IS 10
BP 5201
EP 5211
DI 10.1128/JVI.02318-09
PG 11
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600033
PM 20219919
ER
PT J
AU Nikolenko, GN
Delviks-Frankenberry, KA
Pathak, VK
AF Nikolenko, Galina N.
Delviks-Frankenberry, Krista A.
Pathak, Vinay K.
TI A Novel Molecular Mechanism of Dual Resistance to Nucleoside and
Nonnucleoside Reverse Transcriptase Inhibitors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNASE-H ACTIVITY; PRIMER GRIP REGION;
RIBONUCLEASE-H; CONNECTION DOMAIN; DRUG-RESISTANCE; BINDING POCKET;
NEVIRAPINE RESISTANCE; CLEAVAGE SPECIFICITY; CONFERS ZIDOVUDINE
AB Recently, mutations in the connection subdomain (CN) and RNase H domain of HIV-1 reverse transcriptase (RT) were observed to exhibit dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). To elucidate the mechanism by which CN and RH mutations confer resistance to NNRTIs, we hypothesized that these mutations reduce RNase H cleavage and provide more time for the NNRTI to dissociate from the RT, resulting in the resumption of DNA synthesis and enhanced NNRTI resistance. We observed that the effect of the reduction in RNase H cleavage on NNRTI resistance is dependent upon the affinity of each NNRTI to the RT and further influenced by the presence of NNRTI-binding pocket (BP) mutants. D549N, Q475A, and Y501A mutants, which reduce RNase H cleavage, enhance resistance to nevirapine (NVP) and delavirdine (DLV), but not to efavirenz (EFV) and etravirine (ETR), consistent with their increase in affinity for RT. Combining the D549N mutant with NNRTI BP mutants further increases NNRTI resistance from 3- to 30-fold, supporting the role of NNRTI-RT affinity in our NNRTI resistance model. We also demonstrated that CNs from treatment-experienced patients, previously reported to enhance NRTI resistance, also reduce RNase H cleavage and enhance NNRTI resistance in the context of the patient RT pol domain or a wild-type pol domain. Together, these results confirm key predictions of our NNRTI resistance model and provide support for a unifying mechanism by which CN and RH mutations can exhibit dual NRTI and NNRTI resistance.
C1 [Nikolenko, Galina N.; Delviks-Frankenberry, Krista A.; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, POB B,Bldg 535,Room 334, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 60
TC 31
Z9 32
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 MAY
PY 2010
VL 84
IS 10
BP 5238
EP 5249
DI 10.1128/JVI.01545-09
PG 12
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600037
PM 20219933
ER
PT J
AU Mbisa, JL
Bu, W
Pathak, VK
AF Mbisa, Jean L.
Bu, Wei
Pathak, Vinay K.
TI APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different
Mechanisms
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE TRANSCRIPTION; TYPE-1 VIF;
IN-VIVO; CYTIDINE DEAMINATION; ANTIVIRAL ACTIVITY; RETROVIRAL INFECTION;
ENZYME APOBEC3G; VIRAL-RNA; REPLICATION
AB APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81: 7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using Southern blot analysis. A3G generates a 6-bp extension at the viral U5 end of the 3' long terminal repeat (3'-LTR), which is a poor substrate for integration; in contrast, A3F inhibits viral DNA integration by reducing the 3' processing of viral DNA at both the U5 and U3 ends. Furthermore, we demonstrated that a functional C-terminal catalytic domain is more critical for A3G than A3F function in blocking HIV-1 provirus formation. Finally, we showed that A3F has a greater binding affinity for a viral 3'-LTR double-stranded DNA (dsDNA) oligonucleotide template than A3G. Taking these results together, we demonstrated that mechanisms utilized by A3F to prevent HIV-1 viral DNA integration were different from those of A3G, and that their target specificities and/or their affinities for dsDNA may contribute to their distinct mechanisms.
C1 [Mbisa, Jean L.; Bu, Wei; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Bu, Wei] SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Ctr Canc Res, POB B,Bldg 535,Room 334, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
[HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research
(V.K.P. and J.L.M.) and in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E (W.B.).
NR 56
TC 66
Z9 69
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 MAY
PY 2010
VL 84
IS 10
BP 5250
EP 5259
DI 10.1128/JVI.02358-09
PG 10
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600038
PM 20219927
ER
PT J
AU Gottwein, JM
Scheel, TKH
Callendret, B
Li, YP
Eccleston, HB
Engle, RE
Govindarajan, S
Satterfield, W
Purcell, RH
Walker, CM
Bukh, J
AF Gottwein, Judith M.
Scheel, Troels K. H.
Callendret, Benoit
Li, Yi-Ping
Eccleston, Heather B.
Engle, Ronald E.
Govindarajan, Sugantha
Satterfield, William
Purcell, Robert H.
Walker, Christopher M.
Bukh, Jens
TI Novel Infectious cDNA Clones of Hepatitis C Virus Genotype 3a (Strain
S52) and 4a (Strain ED43): Genetic Analyses and In Vivo Pathogenesis
Studies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELL-CULTURE-SYSTEMS; COMPLETE NUCLEOTIDE-SEQUENCE; CD8(+) T-CELLS;
VIRAL CLEARANCE; MOLECULAR CLONE; IMMUNE-RESPONSES; IMMUNOLOGICAL
DETERMINANTS; NONCODING REGION; CHIMPANZEES; REPLICATION
AB Previously, RNA transcripts of cDNA clones of hepatitis C virus (HCV) genotypes 1a (strains H77, HCV-1, and HC-TN), 1b (HC-J4, Con1, and HCV-N), and 2a (HC-J6 and JFH1) were found to be infectious in chimpanzees. However, only JFH1 was infectious in human hepatoma Huh7 cells. We performed genetic analysis of HCV genotype 3a (strain S52) and 4a (strain ED43) prototype strains and generated full-length consensus cDNA clones (pS52 and pED43). Transfection of Huh7.5 cells with RNA transcripts of these clones did not yield cells expressing HCV Core. However, intrahepatic transfection of chimpanzees resulted in robust infection with peak HCV RNA titers of similar to 5.5 log(10) international units (IU)/ml. Genomic consensus sequences recovered from serum at the times of peak viral titers were identical to the sequences of the parental plasmids. Both chimpanzees developed acute hepatitis with elevated liver enzymes and significant necroinflammatory liver changes coinciding with detection of gamma interferon-secreting, intrahepatic T cells. However, the onset and broadness of intrahepatic T-cell responses varied greatly in the two animals, with an early (week 4) multispecific response in the ED43-infected animal (3 weeks before the first evidence of viral control) and a late (week 11) response with limited breadth in the S52-infected animal (without evidence of viral control). Autologous serum neutralizing antibodies were not detected during the acute infection in either animal. Both animals became persistently infected. In conclusion, we generated fully functional infectious cDNA clones of HCV genotypes 3a and 4a. Proof of functionality of all genes might further the development of recombinant cell culture systems for these important genotypes.
C1 [Gottwein, Judith M.; Scheel, Troels K. H.; Li, Yi-Ping; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, DK-2650 Hvidovre, Denmark.
[Gottwein, Judith M.; Scheel, Troels K. H.; Li, Yi-Ping; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Gottwein, Judith M.; Scheel, Troels K. H.; Li, Yi-Ping; Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Callendret, Benoit; Eccleston, Heather B.; Walker, Christopher M.] Ohio State Univ, Ctr Vaccines & Immun, Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[Callendret, Benoit; Eccleston, Heather B.; Walker, Christopher M.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Engle, Ronald E.; Purcell, Robert H.; Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA.
[Satterfield, William] MD Anderson Canc Ctr, Michale E Keeling Ctr Comparat Med & Res, Dept Vet Sci, Bastrop, TX USA.
RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@sund.ku.dk
OI Scheel, Troels/0000-0003-1545-4067
FU Copenhagen University Hospital, Hvidovre, Denmark; Lundbeck Foundation;
Novo Nordisk Foundation; Danish Medical Research Council; A.P. Moller
and the Chastine Mc-Kinney Moller Foundation; The Danish Cancer Society;
U.S. Public Health Service [R37 AI47367, U19 AI48231]; NIH/NCRR [U-42];
NIAID [NO1-AO-62713]; NIH; University of Copenhagen; American Liver
Foundation
FX We thank the animal technical staff at the Michale E. Keeling Center for
Comparative Medicine and Research for animal care. We also thank Marisa
St. Claire (NIH) for expert assistance during the intrahepatic
transfection procedures. We are grateful to CTL, especially Alexey
Karulin, Wenji Zhang, and Paul Lehmann, for providing customized
software for automated counting of FFU on an ImmunoSpot series 5 UV
analyzer (CTL Europe GmbH). We thank Jens Ole Nielsen and Ove Andersen
(Copenhagen University Hospital, Hvidovre, Denmark) for their support of
the project.; This work was supported by grants from the Copenhagen
University Hospital, Hvidovre, Denmark (J.M.G. and T.K.H.S.), the
Lundbeck Foundation (J.B.), the Novo Nordisk Foundation (J.M.G. and
J.B.), the Danish Medical Research Council (J.B.), the A.P. Moller and
the Chastine Mc-Kinney Moller Foundation (J.M.G., T.K.H.S., and J.B.),
The Danish Cancer Society (J.M.G. and J.B.), and the U.S. Public Health
Service (R37 AI47367 and U19 AI48231; C.M.W.). This study was also
supported by the NIH/NCRR U-42 Chimpanzee Biomedical Resource Grant
(W.S.), the Intramural Research Program of the NIAID, NIH, and by NIAID
contract NO1-AO-62713. T.K.H.S is the recipient of a Ph.D. stipend from
the Faculty of Health Sciences, University of Copenhagen, B.C. is the
recipient of a Postdoctoral Research Fellowship from the American Liver
Foundation, and J.B. is the recipient of a professorship at the
University of Copenhagen with external funding from the Lundbeck
Foundation.
NR 90
TC 63
Z9 64
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2010
VL 84
IS 10
BP 5277
EP 5293
DI 10.1128/JVI.02667-09
PG 17
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600041
PM 20200247
ER
PT J
AU Harker, JA
Lee, DCP
Yamaguchi, Y
Wang, B
Bukreyev, A
Collins, PL
Tregoning, JS
Openshaw, PJM
AF Harker, James A.
Lee, Debbie C. P.
Yamaguchi, Yuko
Wang, Belinda
Bukreyev, Alexander
Collins, Peter L.
Tregoning, John S.
Openshaw, Peter J. M.
TI Delivery of Cytokines by Recombinant Virus in Early Life Alters the
Immune Response to Adult Lung Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY-SYNCYTIAL-VIRUS; NATURAL-KILLER-CELLS; VIRAL-INFECTIONS;
T-CELLS; BRONCHIOLITIS; REINFECTION; AGE; EOSINOPHILS; DETERMINES;
EXPRESSION
AB Respiratory syncytial virus (RSV) is the main cause of bronchiolitis, the major cause of hospitalization of infants. An ideal RSV vaccine would be effective for neonates, but the immune responses of infants differ markedly from those of adults, often showing a bias toward T-helper 2 (Th2) responses and reduced gamma interferon (IFN-gamma) production. We previously developed recombinant RSV vectors expressing IFN-gamma and interleukin-4 (IL-4) that allow us to explore the role of these key Th1 and Th2 cytokines during infection. The aim of the current study was to explore whether an immunomodulation of infant responses could enhance protection. The expression of IFN-gamma by a recombinant RSV vector (RSV/IFN-gamma) attenuated primary viral replication in newborn mice without affecting the development of specific antibody or T-cell responses. Upon challenge, RSV/IFN-gamma mice were protected from the exacerbated disease observed for mice primed with wild-type RSV; however, antiviral immunity was not enhanced. Conversely, the expression of IL-4 by recombinant RSV did not affect virus replication in neonates but greatly enhanced Th2 immune responses upon challenge without affecting weight loss. These studies demonstrate that it is possible to manipulate infant immune responses by using cytokine-expressing recombinant viruses and that neonatal deficiency in IFN-gamma responses may lead to enhanced disease during secondary infection.
C1 [Harker, James A.; Lee, Debbie C. P.; Yamaguchi, Yuko; Wang, Belinda; Tregoning, John S.; Openshaw, Peter J. M.] Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, Ctr Resp Infect, London W2 1PG, England.
[Harker, James A.; Lee, Debbie C. P.; Yamaguchi, Yuko; Wang, Belinda; Tregoning, John S.; Openshaw, Peter J. M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, MRC & Asthma UK Ctr Allerg Mech Asthma, London W2 1PG, England.
[Bukreyev, Alexander; Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Openshaw, PJM (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, Ctr Resp Infect, Paddington Campus,Norfolk Pl,St Marys Campus, London W2 1PG, England.
EM p.openshaw@imperial.ac.uk
OI Tregoning, John/0000-0001-8093-8741
FU Wellcome Trust (United Kingdom) [071381/Z/03/Z]; Medical Research
Council (United Kingdom); NIAID
FX This work was supported by Wellcome Trust Programme grant 071381/Z/03/Z
(United Kingdom) and a Medical Research Council (United Kingdom)
studentship. A.B. and P.L.C. are funded by an NIAID intramural program.
NR 39
TC 17
Z9 19
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 MAY
PY 2010
VL 84
IS 10
BP 5294
EP 5302
DI 10.1128/JVI.02503-09
PG 9
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600042
PM 20200251
ER
PT J
AU Hoelzer, K
Murcia, PR
Baillie, GJ
Wood, JLN
Metzger, SM
Osterrieder, N
Dubovi, EJ
Holmes, EC
Parrish, CR
AF Hoelzer, Karin
Murcia, Pablo R.
Baillie, Gregory J.
Wood, James L. N.
Metzger, Stephan M.
Osterrieder, Nikolaus
Dubovi, Edward J.
Holmes, Edward C.
Parrish, Colin R.
TI Intrahost Evolutionary Dynamics of Canine Influenza Virus in Naive and
Partially Immune Dogs
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A-VIRUS; HEMAGGLUTININ; HOST; TRANSMISSION; INFECTION; EMERGENCE;
DISEASES
AB The patterns and dynamics of evolution in acutely infecting viruses within individual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naive and partially immune dogs and in naturally infected dogs. Tracing sequence diversity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations sampled on any given day were generally characterized by mean pairwise genetic diversities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence diversity differed between naive and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic diversity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.
C1 [Hoelzer, Karin; Parrish, Colin R.] Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
[Murcia, Pablo R.; Baillie, Gregory J.; Wood, James L. N.] Dept Vet Med, Cambridge Infect Dis Consortium, Cambridge CB3 0ES, England.
[Baillie, Gregory J.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Osterrieder, Nikolaus] Free Univ Berlin, Inst Virol, D-10115 Berlin, Germany.
[Dubovi, Edward J.] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, State Coll, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Parrish, CR (reprint author), Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, James A Baker Inst Anim Hlth, Hungerford Hill Rd, Ithaca, NY 14853 USA.
EM crp3@cornell.edu
RI Wood, James/A-1626-2008; Baillie, Gregory/F-9478-2013;
OI Wood, James/0000-0002-0258-3188; Baillie, Gregory/0000-0002-6130-250X;
Holmes, Edward/0000-0001-9596-3552
FU National Institutes of Health [R01 GM080533]; College of Veterinary
Medicine at Cornell University
FX This study was funded in part by National Institutes of Health grant R01
GM080533 to E.C.H and C.R.P.K.H. was supported by a graduate research
assistantship from the College of Veterinary Medicine at Cornell
University.
NR 20
TC 34
Z9 34
U1 1
U2 11
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 MAY
PY 2010
VL 84
IS 10
BP 5329
EP 5335
DI 10.1128/JVI.02469-09
PG 7
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600045
PM 20219907
ER
PT J
AU Kinjo, T
Ham-Terhune, J
Peloponese, JM
Jeang, KT
AF Kinjo, Takao
Ham-Terhune, Julia
Peloponese, Jean-Marie, Jr.
Jeang, Kuan-Teh
TI Induction of Reactive Oxygen Species by Human T-Cell Leukemia Virus Type
1 Tax Correlates with DNA Damage and Expression of Cellular Senescence
Marker
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HTLV-I TAX; ANAPHASE PROMOTING COMPLEX; GENOMIC INSTABILITY; HUMAN
THIOREDOXIN; KAPPA-B; PROTEIN; ONCOPROTEIN; ARREST; REPAIR;
TRANSFORMATION
AB Human T-cell leukemia virus type 1 (HTLV-1) Tax affects cellular genomic stability and senescence. As yet, the mechanism(s) for these events caused by Tax is incompletely understood. Here, we show that Tax expression in primary human cells induces reactive oxygen species (ROS), which elicits DNA damage and the expression of senescence marker. Treatment with a ROS scavenger or knockdown of Tax expression by small interfering RNA (siRNA) abrogated Tax-induced DNA damage and the expression of senescence marker. Our data suggest that ROS induction explains Tax-induced cellular DNA damage and cellular senescence.
C1 [Kinjo, Takao; Ham-Terhune, Julia; Peloponese, Jean-Marie, Jr.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Kinjo, Takao] Univ Ryukyus, Grad Sch, Div Pathol & Cell Biol, Okinawa 9030215, Japan.
[Kinjo, Takao] Univ Ryukyus, Fac Med, Okinawa 9030215, Japan.
[Kinjo, Takao] Univ Ryukyus, Sch Hlth Sci, Dept Basic Lab Sci, Div Morphol Pathol, Okinawa 9030215, Japan.
[Peloponese, Jean-Marie, Jr.] CNRS, F-34965 Montpellier, France.
[Peloponese, Jean-Marie, Jr.] Univ Montpellier 1, UM5236, Ctr Etud Agents Pathogenes & Biotechnol Sante CPB, F-34965 Montpellier, France.
[Peloponese, Jean-Marie, Jr.] Univ Montpellier 2, CPBS, F-34095 Montpellier, France.
RP Jeang, KT (reprint author), 9000 Rockville Pike,Bldg 4,Room 303, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID, NIH; NIH
FX Work in K.-T.J.'s laboratory is supported through intramural funds from
NIAID, NIH, and from the Intramural AIDS Targeted Antiviral Program
(IATAP) from the office of the Director, NIH.
NR 38
TC 38
Z9 39
U1 0
U2 0
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 MAY
PY 2010
VL 84
IS 10
BP 5431
EP 5437
DI 10.1128/JVI.02460-09
PG 7
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600055
PM 20219913
ER
PT J
AU O'Keefe, BR
Giomarelli, B
Barnard, DL
Shenoy, SR
Chan, PKS
McMahon, JB
Palmer, KE
Barnett, BW
Meyerholz, DK
Wohlford-Lenane, CL
McCray, PB
AF O'Keefe, Barry R.
Giomarelli, Barbara
Barnard, Dale L.
Shenoy, Shilpa R.
Chan, Paul K. S.
McMahon, James B.
Palmer, Kenneth E.
Barnett, Brian W.
Meyerholz, David K.
Wohlford-Lenane, Christine L.
McCray, Paul B., Jr.
TI Broad-Spectrum In Vitro Activity and In Vivo Efficacy of the Antiviral
Protein Griffithsin against Emerging Viruses of the Family Coronaviridae
(vol, 84, pg, 2511, 2010)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [O'Keefe, Barry R.] NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA.
Utah State Univ, Logan, UT 84322 USA.
SAIC Frederick, Frederick, MD 21702 USA.
Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA.
Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40202 USA.
Owensboro Canc Res Program, Owensboro, KY 42303 USA.
Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA.
Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA.
RP O'Keefe, BR (reprint author), NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA.
NR 1
TC 0
Z9 0
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 MAY
PY 2010
VL 84
IS 10
BP 5456
EP 5456
DI 10.1128/VI.00537-10
PG 1
WC Virology
SC Virology
GA 591QW
UT WOS:000277318600060
ER
PT J
AU Enewold, L
Brinton, LA
McGlynn, KA
Zahm, SH
Potter, JF
Zhu, KM
AF Enewold, Lindsey
Brinton, Louise A.
McGlynn, Katherine A.
Zahm, Shelia H.
Potter, John F.
Zhu, Kangmin
TI Oral Contraceptive Use Among Women in the Military and the General US
Population
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID OVARIAN-CANCER RISK; BREAST-CANCER; COLLABORATIVE REANALYSIS;
ENDOMETRIAL CANCER; METAANALYSIS; COHORT; POTENCY
AB Objective: To compare oral contraceptive (OC) use during a 12-month period among women aged 18-39 years in the U. S. military and the general U. S. population using data from the Military Health System Management Analysis and Reporting Tool (M2) and the National Health and Nutrition Examination Survey (NHANES), respectively.
Methods: OC use was age adjusted to the 2000 U. S. Census population. Comparisons between the military (n = 83,181) and the general population (unweighted n = 360), as well as between the military branches, were conducted overall and stratified by age, race/ethnicity, and marital status.
Results: OC use was higher in the military (34%) than in the general population (29%, p<0.05). This difference increased with age and was most pronounced among Hispanics (military, 32.2%; general population, 19.8%). Within the military, OC use was highest in the Air Force (39%) and lowest in the Army (30%, p<0.05).
Conclusions: These findings suggest that OC use differs between the military and the general population and within the military by service branch. Further studies that assess whether OC use is related to variations in health outcomes between these two populations and within the military are warranted.
C1 [Enewold, Lindsey] US Mil Canc Inst, Armed Forces Inst Pathol, Walter Reed Army Med Ctr, Washington, DC 20306 USA.
[Brinton, Louise A.; McGlynn, Katherine A.; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Potter, John F.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA.
RP Enewold, L (reprint author), US Mil Canc Inst, Armed Forces Inst Pathol, Walter Reed Army Med Ctr, Bldg 54,Room N1512,6825 16th St NW, Washington, DC 20306 USA.
EM lindsey.enewold@us.army.mil
RI Zahm, Shelia/B-5025-2015; Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU DCEG; NCI; NIH; Department of Health and Human Services; United States
Military Cancer Institute via the Uniformed Services University of the
Health Sciences
FX This study was partly supported by the Intramural Research Program of
the DCEG, NCI, NIH, Department of Health and Human Services, and by the
United States Military Cancer Institute via the Uniformed Services
University of the Health Sciences under the auspices of the Henry M.
Jackson Foundation for the Advancement of Military Medicine.
NR 42
TC 12
Z9 12
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAY
PY 2010
VL 19
IS 5
BP 839
EP 845
DI 10.1089/jwh.2009.1706
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 595HW
UT WOS:000277602300003
PM 20350205
ER
PT J
AU Gollenberg, AL
Hediger, ML
Mumford, SL
Whitcomb, BW
Hovey, KM
Wactawski-Wende, J
Schisterman, EF
AF Gollenberg, Audra L.
Hediger, Mary L.
Mumford, Sunni L.
Whitcomb, Brian W.
Hovey, Kathleen M.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Perceived Stress and Severity of Perimenstrual Symptoms: The BioCycle
Study
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID PREMENSTRUAL DYSPHORIC DISORDER; PHYSICAL-ACTIVITY; MENSTRUAL-CYCLE;
INTRAINDIVIDUAL PATTERNS; PSYCHOSOCIAL STRESS; FERTILITY MONITOR;
OVARIAN-STEROIDS; UNITED-STATES; LEISURE-TIME; WOMEN
AB Objective: To examine the longitudinal relation between perceived stress in the previous month and perimenstrual symptom severity across two cycles among regularly menstruating, healthy women (n = 259).
Methods: At baseline (11 days before the first cycle), participants completed the 4-item Perceived Stress Scale (PSS) for the previous month (first cycle exposure) and questionnaires on lifestyle factors. On cycle day 22 of a standardized 28-day cycle, participants again completed the PSS for the previous week (second cycle exposure) and each week rated the severity (none, mild, moderate, severe) of 17 psychological and physical symptoms (e. g., crying, cramping, pain). Mixed models estimated the association between perceived stress scores and number of moderate/severe symptoms and symptom severity scores, allowing both stress and perimenstrual symptoms to vary by cycle.
Results: Adjusting for age, education, passive and active smoking, and waist/height ratio (WHtR), high stress (fourth quartile PSS) was associated with an increased risk of reporting >= 8 or more (OR 7.2, 3.3-15.8) and >= 5 (OR 2.5, 1.6-4.1) symptoms as moderate/severe during the perimenstrual period compared with lower stress (quartiles one, two, and three). Stress scores were positively (p < 0.0001) associated with increased symptom severity scores for total, psychological, and physical symptoms.
Conclusions: These analyses show that higher perceived stress precedes an increased severity of perimenstrual symptoms. Stress reduction programs may be an effective, nonpharmaceutical treatment for physical and psychological symptom relief.
C1 [Gollenberg, Audra L.; Hediger, Mary L.; Mumford, Sunni L.; Schisterman, Enrique F.] NICHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD USA.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Publ Hlth, Amherst, MA 01003 USA.
[Hovey, Kathleen M.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Gollenberg, AL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B03, Rockville, MD 20892 USA.
EM gollenba@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We are indebted to all the investigators and staff at the Epidemiology
Branch, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, and the University at Buffalo for their respective
roles in the study, their dedication and effort, and assistance in study
implementation. In addition, we recognize the BioCycle participants for
their extraordinary commitment to the study.; This work was funded by
intramural funds from the Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Results were presented at the Annual
Meeting of the Society of Pediatric and Perinatal Epidemiologic
Research, Anaheim, California, June 22-23, 2009.
NR 64
TC 10
Z9 10
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAY
PY 2010
VL 19
IS 5
BP 959
EP 967
DI 10.1089/jwh.2009.1717
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 595HW
UT WOS:000277602300018
PM 20384452
ER
PT J
AU Smith, DL
Elam, CF
Mattison, JA
Lane, MA
Roth, GS
Ingram, DK
Allison, DB
AF Smith, Daniel L., Jr.
Elam, Calvin F., Jr.
Mattison, Julie A.
Lane, Mark A.
Roth, George S.
Ingram, Donald K.
Allison, David B.
TI Metformin Supplementation and Life Span in Fischer-344 Rats
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Calorie restriction; Metformin; Mimetic; Life span; Aging
ID HER-2/NEU TRANSGENIC MICE; CALORIE RESTRICTION MIMETICS;
GENE-EXPRESSION; MAMMARY-TUMORS; LONGEVITY; HUMANS; DIPHENYLHYDANTOIN;
PHENFORMIN; BIOMARKERS; GROWTH
AB Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.
C1 [Elam, Calvin F., Jr.; Allison, David B.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Smith, Daniel L., Jr.; Allison, David B.] Univ Alabama, Dept Nutr Sci, Birmingham, AL USA.
[Smith, Daniel L., Jr.; Allison, David B.] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL USA.
[Mattison, Julie A.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Lane, Mark A.] MedImmune LLC, Gaithersburg, MD USA.
[Roth, George S.] GeroScience Inc, Pylesville, MD USA.
[Ingram, Donald K.] Louisiana State Univ Syst, Nutr Neurosci & Aging Lab, Pennington Biomed Res Ctr, Baton Rouge, LA USA.
RP Allison, DB (reprint author), Univ Alabama, Dept Biostat, Ryals Publ Hlth Bldg,Suite 414,1665 Univ Blvd, Birmingham, AL 35294 USA.
EM Dallison@uab.edu
OI Allison, David/0000-0003-3566-9399
FU National Institutes of Health, National Institute on Aging; National
Institute on Aging to TherImmune Research Corporation [T32DK062710]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. This
work was performed under a contract from the National Institute on Aging
to TherImmune Research Corporation (now GeneLogic, Gaithersburg, MD).
D.L.S. was supported by T32DK062710.
NR 47
TC 50
Z9 51
U1 0
U2 6
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2010
VL 65
IS 5
BP 468
EP 474
DI 10.1093/gerona/glq033
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 589BY
UT WOS:000277120700002
PM 20304770
ER
PT J
AU Newman, AB
Walter, S
Lunetta, KL
Garcia, ME
Slagboom, PE
Christensen, K
Arnold, AM
Aspelund, T
Aulchenko, YS
Benjamin, EJ
Christiansen, L
D'Agostino, RB
Fitzpatrick, AL
Franceschini, N
Glazer, NL
Gudnason, V
Hofman, A
Kaplan, R
Karasik, D
Kelly-Hayes, M
Kiel, DP
Launer, LJ
Marciante, KD
Massaro, JM
Miljkovic, I
Nalls, MA
Hernandez, D
Psaty, BM
Rivadeneira, F
Rotter, J
Seshadri, S
Smith, AV
Taylor, KD
Tiemeier, H
Uh, HW
Uitterlinden, AG
Vaupel, JW
Walston, J
Westendorp, RGJ
Harris, TB
Lumley, T
van Duijn, CM
Murabito, JM
AF Newman, Anne B.
Walter, Stefan
Lunetta, Kathryn L.
Garcia, Melissa E.
Slagboom, P. Eline
Christensen, Kaare
Arnold, Alice M.
Aspelund, Thor
Aulchenko, Yurii S.
Benjamin, Emelia J.
Christiansen, Lene
D'Agostino, Ralph B., Sr.
Fitzpatrick, Annette L.
Franceschini, Nora
Glazer, Nicole L.
Gudnason, Vilmundur
Hofman, Albert
Kaplan, Robert
Karasik, David
Kelly-Hayes, Margaret
Kiel, Douglas P.
Launer, Lenore J.
Marciante, Kristin D.
Massaro, Joseph M.
Miljkovic, Iva
Nalls, Michael A.
Hernandez, Dena
Psaty, Bruce M.
Rivadeneira, Fernando
Rotter, Jerome
Seshadri, Sudha
Smith, Albert V.
Taylor, Kent D.
Tiemeier, Henning
Uh, Hae-Won
Uitterlinden, Andre G.
Vaupel, James W.
Walston, Jeremy
Westendorp, Rudi G. J.
Harris, Tamara B.
Lumley, Thomas
van Duijn, Cornelia M.
Murabito, Joanne M.
TI A Meta-analysis of Four Genome-Wide Association Studies of Survival to
Age 90 Years or Older: The Cohorts for Heart and Aging Research in
Genomic Epidemiology Consortium
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Longevity; Genome-wide association study; Meta-analysis
ID EXCEPTIONAL LONGEVITY; PLASMA-PROTEIN; LIFE-SPAN; CARDIOVASCULAR HEALTH;
LEIDEN LONGEVITY; OXIDATIVE STRESS; PROSTATE-CANCER; BREAST-CANCER;
FRAMINGHAM; GENE
AB Background. Genome-wide association studies (GWAS) may yield insights into longevity.
Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (a = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort.
Results. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPPI (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage.
Conclusion. Survival studies of larger size or more extreme or specific phenotypes may support or reline these initial findings.
C1 [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Cardiovasc Hlth Study, Pittsburgh, PA 15213 USA.
[Walter, Stefan; Aulchenko, Yurii S.; Tiemeier, Henning; Uitterlinden, Andre G.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Walter, Stefan] Erasmus MC, Dept Epidemiol & Biostat, Rotterdam Study, Rotterdam, Netherlands.
[Lunetta, Kathryn L.; D'Agostino, Ralph B., Sr.; Kelly-Hayes, Margaret; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Framingham Heart Study, Dept Biostat, Boston, MA 02215 USA.
[Garcia, Melissa E.; Harris, Tamara B.] NIA, AGES Reykjavik Study, Lab Epidemiol Biometry & Demog, Intramural Res Program, Bethesda, MD 20892 USA.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden Longev Study,Netherlands Consortium Hlth A, NL-2300 RA Leiden, Netherlands.
[Christensen, Kaare] Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, Odense, Denmark.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Sch Med, AGES Reykjavik, Reykjavik, Iceland.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Cardiol, Framingham Heart Study, Boston, MA 02215 USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Sch Med, Stat & Consulting Unit, Framingham Heart Study, Boston, MA 02215 USA.
[Fitzpatrick, Annette L.] Univ N Carolina, Dept Epidemiol, Atherosclerosis Risk Communities Study, Chapel Hill, NC USA.
[Glazer, Nicole L.; Marciante, Kristin D.] Univ Washington, Cardiovasc Hlth Res Unit, Cardiovasc Hlth Study, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Smith, Albert V.] Univ Washington, Dept Med, Seattle, WA USA.
[Gudnason, Vilmundur] Iceland Heart Assoc, AGES Reykjavik, Reykjavik, Iceland.
[Kaplan, Robert] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Cardiovascr Hlth Study, Bronx, NY 10467 USA.
[Karasik, David; Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Framingham Heart Study, Boston, MA USA.
[Karasik, David] Harvard Univ, Sch Med, Boston, MA USA.
[Kelly-Hayes, Margaret] Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02215 USA.
[Hernandez, Dena] NIA, Intramural Res Program, Neurogenet Lab, AGES Reykjavik, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Cardiovasc Hlth Study, Seattle, WA USA.
[Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam Study, Rotterdam, Netherlands.
[Rotter, Jerome] Cedars Sinai Med Ctr, Inst Med Genet, Cardiovasc Hlth Study, Los Angeles, CA 90048 USA.
[Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam Study, Rotterdam, Netherlands.
[Tiemeier, Henning] Sophia Childrens Univ Hosp, Rotterdam, Netherlands.
[Uh, Hae-Won] Leiden Univ, Med Ctr, Sect Med Stat, Leiden Longev Study,Netherlands Consortium Hlth A, NL-2300 RA Leiden, Netherlands.
[Vaupel, James W.] Duke Univ, Populat Policy & Aging Res Ctr, Durham, NC USA.
[Walston, Jeremy] Johns Hopkins Univ, Dept Med, Cardiovasc Hlth Study, Baltimore, MD USA.
[Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol, Leiden Longev Study, NL-2300 RA Leiden, Netherlands.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Framingharn Heart Study, Boston, MA 02215 USA.
RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Cardiovasc Hlth Study, 130 N Bellefield Ave,Suite 500, Pittsburgh, PA 15213 USA.
EM newmana@edc.pitt.edu
RI Christensen, Kaare/C-2360-2009; Aspelund, Thor/F-4826-2011; Aspelund,
Thor/C-5983-2008; Aulchenko, Yurii/M-8270-2013; Newman,
Anne/C-6408-2013; Gudnason, Vilmundur/K-6885-2015; Rivadeneira,
Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Slagboom, P.
Eline/R-4790-2016;
OI Karasik, David/0000-0002-8826-0530; Christensen,
Kaare/0000-0002-5429-5292; Aspelund, Thor/0000-0002-7998-5433;
Aulchenko, Yurii/0000-0002-7899-1575; Newman, Anne/0000-0002-0106-1150;
Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Slagboom, P. Eline/0000-0002-2875-4723; Massaro,
Joseph/0000-0002-2682-4812; Lunetta, Kathryn/0000-0002-9268-810X;
Murabito, Joanne/0000-0002-0192-7516; Seshadri,
Sudha/0000-0001-6135-2622; Miljkovic, Iva/0000-0002-3155-9777; Tiemeier,
Henning/0000-0002-4395-1397; Benjamin, Emelia/0000-0003-4076-2336; Kiel,
Douglas/0000-0001-8474-0310
FU NIA NIH HHS [P30 AG024827]; NIDDK NIH HHS [K01 DK083029, K01
DK083029-02]
NR 56
TC 63
Z9 67
U1 0
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 MAY
PY 2010
VL 65
IS 5
BP 478
EP 487
DI 10.1093/gerona/glq028
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 589BY
UT WOS:000277120700003
PM 20304771
ER
PT J
AU Shea, MK
Houston, DK
Nicklas, BJ
Messier, SP
Davis, CC
Miller, ME
Harris, TB
Kitzman, DW
Kennedy, K
Kritchevsky, SB
AF Shea, M. Kyla
Houston, Denise K.
Nicklas, Barbara J.
Messier, Stephen P.
Davis, Cralen C.
Miller, Michael E.
Harris, Tamara B.
Kitzman, Dalane W.
Kennedy, Kimberly
Kritchevsky, Stephen B.
TI The Effect of Randomization to Weight Loss on Total Mortality in Older
Overweight and Obese Adults: The ADAPT Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Intentional weight loss; Mortality; Aging; Obesity
ID AGED 40-64 YEARS; NATIONAL DEATH INDEX; DISEASE RISK-FACTORS; ALL-CAUSE
MORTALITY; IOWA WOMENS HEALTH; US ADULTS; MEN; TRIAL; INTENTIONALITY;
ASSOCIATIONS
AB Background. Although weight loss reduces risk for comorbid diseases, many observational studies suggest that weight loss is associated with increased mortality risk, leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults. However, whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction. Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used to determine whether randomization to a weight reduction program was associated with total mortality in overweight/obese older adults.
Methods. ADAPT (n = 318; mean age 69 +/- 6 years, body mass index 34 +/- 5 kg/m(2), 72% female) assessed the influence of weight loss (achieved through dietary counseling and lifestyle modification) and/or exercise on function in overweight/obese older adults with knee osteoarthritis. ADAPT ended in December 1999. Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes.
Results. The mortality rate for those randomized to the 18-month weight loss intervention (n = 159, mean weight loss = -4.8 kg, 15 deaths) was lower than that for those not randomized to the weight loss intervention (n =- 159, mean weight loss = -1.4 kg, 30 deaths; hazard rate ratio = 0.5, 95% confidence interval 0.3-1.0). Results were not appreciably changed when analyses were stratified by age, gender, baseline weight status, or magnitude of weight loss.
Conclusions. In older adults, intentional weight loss was not associated with increased total mortality and may reduce mortality risk. Observational studies of weight loss, especially when intentionality cannot be rigorously established, may be misleading with respect to the effect of weight loss on mortality.
C1 [Shea, M. Kyla] Wake Forest Univ, Sticht Ctr Aging, Dept Internal Med, Sect Gerontol & Geriatr Med,Sch Med, Winston Salem, NC 27109 USA.
[Davis, Cralen C.; Miller, Michael E.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA.
RP Shea, MK (reprint author), Wake Forest Univ, Sticht Ctr Aging, Dept Internal Med, Sect Gerontol & Geriatr Med,Sch Med, Med Ctr Blvd, Winston Salem, NC 27109 USA.
EM kshea@wfubmc.edu
OI Kritchevsky, Stephen/0000-0003-3336-6781
FU Wake Forest University Claude D. Pepper Older Americans Independence
Center [P30-AG21332]
FX This work was supported by the Wake Forest University Claude D. Pepper
Older Americans Independence Center (P30-AG21332).
NR 25
TC 47
Z9 51
U1 2
U2 7
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2010
VL 65
IS 5
BP 519
EP 525
DI 10.1093/gerona/glp217
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 589BY
UT WOS:000277120700009
PM 20080875
ER
PT J
AU Fuller-Thomson, E
Yu, B
Nuru-Jeter, A
Guralnik, JM
Minkler, M
AF Fuller-Thomson, E.
Yu, B.
Nuru-Jeter, A.
Guralnik, J. M.
Minkler, M.
TI UNADJUSTED PREVALENCE RATES: WHY THEY STILL MATTER FOR OLDER ADULTS'
DISABILITY RATES
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Letter
C1 [Fuller-Thomson, E.] Univ Toronto, Factor Inwentash Fac Social Work, Toronto, ON M5S 1A1, Canada.
[Fuller-Thomson, E.] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada.
[Yu, B.; Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Nuru-Jeter, A.; Minkler, M.] Univ Calif Berkeley, Div Community Hlth & Human Dev, Berkeley, CA 94720 USA.
RP Fuller-Thomson, E (reprint author), Univ Toronto, Factor Inwentash Fac Social Work, 246 Bloor St W, Toronto, ON M5S 1A1, Canada.
EM esme.fuller.thomson@utoronto.ca
NR 4
TC 1
Z9 1
U1 0
U2 0
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2010
VL 65
IS 5
BP 545
EP 546
DI 10.1093/gerona/glq031
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 589BY
UT WOS:000277120700013
PM 20231215
ER
PT J
AU Zuliani, G
Cavalieri, M
Galvani, M
Volpato, S
Cherubini, A
Bandinelli, S
Corsi, AM
Lauretani, F
Guralnik, JM
Fellin, R
Ferrucci, L
AF Zuliani, G.
Cavalieri, M.
Galvani, M.
Volpato, S.
Cherubini, A.
Bandinelli, S.
Corsi, A. M.
Lauretani, F.
Guralnik, J. M.
Fellin, R.
Ferrucci, L.
TI Relationship Between Low Levels of High-Density Lipoprotein Cholesterol
and Dementia in the Elderly. The InChianti Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Dementia; Lipids; Elderly
ID APOLIPOPROTEIN-E POLYMORPHISM; ALZHEIMERS-DISEASE; PLASMA-LIPIDS;
COGNITIVE IMPAIRMENT; SERUM CONCENTRATION; VASCULAR DEMENTIA; OLDER
PERSONS; RISK-FACTORS; LIFE; RESTRICTION
AB Background. To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals.
Methods. A total of 1051 older community-dwelling individuals (age >= 65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years.
Results. At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis. HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99). but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle brachial index.
Conclusions. Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels.
C1 [Zuliani, G.; Cavalieri, M.; Galvani, M.; Fellin, R.] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy.
[Cherubini, A.] Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Ferrucci, L.] ASF Geriatr Rehabil, Florence, Italy.
[Bandinelli, S.; Corsi, A. M.] Univ Florence, Dept Med & Surg Crit Care, Ctr Study Mol Level Chron Degenerat & Neoplast Di, Florence, Italy.
[Lauretani, F.] Univ Hosp Parma, Geriatr Rehabil Dept, Geriatr Unit & Clin Geriatr, Parma, Italy.
[Guralnik, J. M.; Ferrucci, L.] NIA, Clin Res Branch, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA.
[Zuliani, G.; Fellin, R.] Ctr Esperto Malattia Alzheimer Perusini, Ferrara, Italy.
RP Zuliani, G (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy.
EM gzuliani@hotmail.com
RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016;
OI VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani,
Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897
FU Italian Ministry of Health [ICS 110.1/RF97.71]; US National Institute on
Aging
FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted
project" (ICS 110.1/RF97.71) by the Italian Ministry of Health and in
part by the US National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336). The InCHIANTI Follow-up 1(2001-2003) was funded by the
US National Institute on Aging (Contracts: N.1-AG-1-1 and N.1AG-1-2111).
NR 40
TC 17
Z9 18
U1 1
U2 5
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2010
VL 65
IS 5
BP 559
EP 564
DI 10.1093/gerona/glq026
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 589BY
UT WOS:000277120700016
PM 20299544
ER
PT J
AU Zorov, DB
AF Zorov, Dmitry B.
TI Amelioration of aminoglycoside nephrotoxicity requires protection of
renal mitochondria
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID PERMEABILITY TRANSITION
AB Cytotoxic effects of some therapeutic drugs, including those used for antibacterial treatment, can involve mitochondria by inducing their permeabilization, followed by cell death and organ malfunctioning. This suggests that a strategy to preserve tissue mitochondria could preserve normal organ functioning. Morales et al. reveal that the antidiabetic drug metformin prevents gentamicin-induced nephropathy through a mitochondria-dependent pathway, normalizing oxidative stress and restoring mitochondrial functional integrity. Kidney International (2010) 77, 841-843. doi:10.1038/ki.2010.20
C1 [Zorov, Dmitry B.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Dept Bioenerget, Moscow 119991, Russia.
[Zorov, Dmitry B.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Zorov, DB (reprint author), Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Dept Bioenerget, Moscow 119991, Russia.
EM zorov@genebee.msu.su
FU Intramural NIH HHS
NR 10
TC 18
Z9 21
U1 0
U2 2
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 MAY
PY 2010
VL 77
IS 10
BP 841
EP 843
DI 10.1038/ki.2010.20
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 589RF
UT WOS:000277169800001
PM 20431573
ER
PT J
AU Rosansky, SJ
Glassock, RJ
Eggers, PW
Clark, WF
AF Rosansky, Steven J.
Glassock, Richard J.
Eggers, Paul W.
Clark, William F.
TI The CANUSA study and the importance of residual kidney function in
dialysis patients Reply
SO KIDNEY INTERNATIONAL
LA English
DT Letter
C1 [Rosansky, Steven J.] WJBD VA Hosp, Dept Nephrol, Columbia, SC 29209 USA.
[Glassock, Richard J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Laguna Niguel, CA USA.
[Eggers, Paul W.] NIDDK, Dept Digest & Kidney Dis, Kidney & Urol Branch, Bethesda, MD USA.
[Clark, William F.] London Hlth Sci Ctr, Dept Med, London, ON, Canada.
RP Rosansky, SJ (reprint author), WJBD VA Hosp, Dept Nephrol, 6439 Garners Ferry Rd, Columbia, SC 29209 USA.
EM sjrcra@yahoo.com
NR 2
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 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAY
PY 2010
VL 77
IS 10
BP 931
EP 932
DI 10.1038/ki.2010.36
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 589RF
UT WOS:000277169800021
ER
PT J
AU Taschner-Mandl, S
Kowalska, A
Binder, H
Rieder, D
Trajanoski, Z
Khan, J
Speleman, F
Ambros, I
Ambros, P
AF Taschner-Mandl, S.
Kowalska, A.
Binder, H.
Rieder, D.
Trajanoski, Z.
Khan, J.
Speleman, F.
Ambros, I
Ambros, P.
TI Hydroxyurea induces a senescent, non-malignant, immunogenic state in
neuroblastoma cells - a new therapeutic strategy?
SO KLINISCHE PADIATRIE
LA English
DT Meeting Abstract
C1 [Taschner-Mandl, S.; Kowalska, A.; Binder, H.; Ambros, I; Ambros, P.] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria.
[Rieder, D.; Trajanoski, Z.] Med Univ Innsbruck, Innsbruck, Austria.
[Khan, J.] NCI, NIH, Washington, DC USA.
[Speleman, F.] Ghent Univ Hosp, B-9000 Ghent, Belgium.
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 0300-8630
J9 KLIN PADIATR
JI Klinische Padiatr.
PD MAY-JUN
PY 2010
VL 222
IS 3
MA 44
BP 224
EP 224
PG 1
WC Pediatrics
SC Pediatrics
GA 612MV
UT WOS:000278903900071
ER
PT J
AU Byrne, KM
Booth, GS
Lee, JY
Ravenell, KR
AF Byrne, Karen M.
Booth, Garrett S.
Lee, Jae Y.
Ravenell, Kanaeko R.
TI The Importance of Antibody Detection and Identification in the
Chronically Transfused Patient
SO LABMEDICINE
LA English
DT Editorial Material
DE blood banking/transfusion medicine
ID ALLOIMMUNIZATION
AB Clinical History
Patient: A 44-year-old, African-American female with sickle cell disease (SCD) presented for evaluation of pulmonary hypertension.
Past Medical History: Sickle cell disease, pulmonary hypertension, hepatitis C (genotype 2), iron overload secondary to transfusion, hypothyroidism, and human leukocyte antigen (HLA)-alloimmunization due to multiple blood product transfusions for a simple transfusion every 3 weeks.
Past Immunohematology History: Patient's RBCs phenotyped as group A, Rh positive, C-E+c+e+, K:-1, Fy(a(-b-)), Jk((a+b-)), and S-s+. Red blood units transfused were ABO-compatible and negative for C and K antigens as per hospital policy to transfuse Rh- and K-matched RBC to patients with SCD. One month later, anti-Swain-Langley (SI(a)) was identified (Figure 1). This antibody is considered clinically insignificant and reactivity was observed when testing with polyethylene glycol (PEG) and low ionic-strength saline (LISS) showed <1+ reactivity with all cells tested except for the SI(a) antigen negative red cell. SI(a) is an antigen in the Knops blood group system and is destroyed by 0.2 M dithiothreitol (DTT). This technique was used, and the chemically-treated cells were used to rule out additional antibodies. Care must be taken when performing rule outs using 0.2 M OTT-treated cells because antigens other than SI(a) are destroyed. Antigens usually denatured or altered include Yt(a), JMH, Knops, LW, Kell, Lutheran, Dombrock, and Cromer blood group antigens.' The patient remained on C and K antigen negative restrictions and received units that were crossmatch-incompatible due to the anti-SI(a). Approximately 3 years later, an antibody screen was performed (Figure 2), and anti-S was suspected. Additional testing confirmed the new antibody. After the identification of anti-S the patient was restricted to receive phenotypically-matched (ABO/Rh-compatible, C, K1, Fy(a), Jk(b) and S negative) RBC units. It was decided not to give units negative for the Fy(b) antigen since it is common for Africans who phenotype as Fy((a-b-)) to carry a variant Fyb allele, which carries a mutation within a GATA consensus sequence preventing expression of the gene in the erythroid cells but not other cells.(2)
Physical Exam
Vitals: Temperature was 36.7 degrees C, heart rate was 70 bpm, blood pressure was 119/74, weight was 84.1 kg, 02 saturation was 95%, and room air=yes.
General: No acute distress, interactive.
Head/Eyes/Ears/Nose/Throat (HEENT): Normocephalic, pupils equal, round and reactive to light, extraocular movements intact, mouth without erythema, lesions, or exudates, no jugular venous distention, and no carotid bruits.
Pulmonary: Clear to auscultation bilaterally, no rates, rhonchi, or wheezing, good aeration.
Cardiovascular: Regular rate and rhythm.
Extremities: No edema, no cyanosis, 1+ digital clubbing.
Current Immunohematology Findings: Patient continued to receive phenotypically matched RBC units. Tie most recent sample indicates a third antibody is present. Reactivity with 2 S-negative cells was noted to be 3+, while all other S negative, SIa positive cells were 1+ in PEG and LISS (Figure 3). Two Jsa positive cells (2 and 8), reacted 3+ with patient plasma in both PEG arid LISS, yet no reactivity was observed with DTT-treated cells. Anti-Jsa was suspected and confirmed.
C1 [Byrne, Karen M.; Booth, Garrett S.; Lee, Jae Y.; Ravenell, Kanaeko R.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Byrne, KM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM kbyrne@cc.nih.gov
NR 8
TC 0
Z9 0
U1 1
U2 3
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0007-5027
J9 LABMEDICINE
JI Labmedicine
PD MAY
PY 2010
VL 41
IS 5
BP 261
EP 263
DI 10.1309/LM4ZQD8J8HHEN0NV
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 587HJ
UT WOS:000276980800001
ER
PT J
AU DeLeo, FR
Otto, M
Kreiswirth, BN
Chambers, HF
AF DeLeo, Frank R.
Otto, Michael
Kreiswirth, Barry N.
Chambers, Henry F.
TI Community-associated meticillin-resistant Staphylococcus aureus
SO LANCET
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; CASSETTE CHROMOSOME MEC; SOFT-TISSUE
INFECTIONS; METHICILLIN-RESISTANT; UNITED-STATES; DOUBLE-BLIND;
RISK-FACTORS; NASAL CARRIAGE; ALPHA-TOXIN; TRIMETHOPRIM-SULFAMETHOXAZOLE
AB Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.
C1 [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[DeLeo, Frank R.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Kreiswirth, Barry N.] Univ Med & Dent New Jersey, Publ Hlth Res Inst, TB Ctr, Int Ctr Publ Hlth, Newark, NJ 07103 USA.
[Chambers, Henry F.] Univ Calif San Francisco, Div Infect Dis, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115
FU US Public Health Service [AI070289]; National Institutes of Health,
National Institutes of Allergy and Infectious Diseases
FX This Seminar was supported by the US Public Health Service Grant
AI070289 (HFC) and the Intramural Research Program of the National
Institutes of Health, National Institutes of Allergy and Infectious
Diseases (FRD and MO). We thank Scott Kobayashi for critical review of
the Seminar.
NR 155
TC 541
Z9 551
U1 6
U2 82
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAY 1
PY 2010
VL 375
IS 9725
BP 1557
EP 1568
DI 10.1016/S0140-6736(09)61999-1
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 596AH
UT WOS:000277655100029
PM 20206987
ER
PT J
AU Feldmann, H
AF Feldmann, Heinz
TI Are we any closer to combating Ebola infections?
SO LANCET
LA English
DT Editorial Material
ID POSTEXPOSURE TREATMENT; VIRUS; FEVER
C1 [Feldmann, Heinz] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 14
TC 7
Z9 7
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD MAY-JUN
PY 2010
VL 375
IS 9729
BP 1850
EP 1852
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 609BC
UT WOS:000278628800006
PM 20511001
ER
PT J
AU Donald, PR
Marais, BJ
Barry, CE
AF Donald, Peter R.
Marais, Ben J.
Barry, Clifton E., III
TI Age and the epidemiology and pathogenesis of tuberculosis
SO LANCET
LA English
DT Editorial Material
ID CHILDHOOD TUBERCULOSIS; IMMUNITY; DEFECTS; CELLS
C1 [Donald, Peter R.; Marais, Ben J.] Univ Stellenbosch, Fac Hlth Sci, Dept Paediat & Child Hlth, ZA-7505 Tygerberg, South Africa.
[Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Donald, PR (reprint author), Univ Stellenbosch, Fac Hlth Sci, Dept Paediat & Child Hlth, ZA-7505 Tygerberg, South Africa.
EM prd@sun.ac.za
RI Barry, III, Clifton/H-3839-2012
NR 15
TC 61
Z9 65
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD MAY-JUN
PY 2010
VL 375
IS 9729
BP 1852
EP 1854
DI 10.1016/S0140-6736(10)60580-6
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 609BC
UT WOS:000278628800007
PM 20488519
ER
PT J
AU Ramakrishnan, M
Moisi, JC
Klugman, KP
Iglesias, JMF
Grant, LR
Mpoudi-Etame, M
Levine, OS
AF Ramakrishnan, Meenakshi
Moisi, Jennifer C.
Klugman, Keith P.
Feris Iglesias, Jesus M.
Grant, Lindsay R.
Mpoudi-Etame, Mireille
Levine, Orin S.
TI Increased risk of invasive bacterial infections in African people with
sickle-cell disease: a systematic review and meta-analysis
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID PNEUMOCOCCAL CONJUGATE VACCINE; HEMOGLOBIN DISORDERS; SEVERE ANEMIA;
YOUNG-ADULTS; CHILDREN; BACTEREMIA; PROPHYLAXIS; MORTALITY;
EPIDEMIOLOGY; FORMULATION
AB Children with sickle-cell disease are at great risk of serious infections and early mortality. Our Review investigates the association between sickle-cell disease and invasive bacterial disease among populations in Africa. We systematically searched published work extracted data on pneumonia, meningitis, and bacteraemia by sickle-cell disease status. Most studies identified lacked a control group and did not use best laboratory methods for culturing fastidious bacteria. Only seven case-control or case-cohort studies provided data on the association between invasive bacterial disease and sickle-cell disease status. For all-cause laboratory-confirmed invasive bacterial disease, the pooled odds of sickle-cell disease was 19-times greater among cases than controls. For disease caused by Streptococcus pneumoniae, the pooled odds of sickle-cell disease was 36-times greater; and for Haemophilus influenzae type b disease it was 13-times greater.
C1 [Moisi, Jennifer C.; Grant, Lindsay R.; Levine, Orin S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Klugman, Keith P.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Klugman, Keith P.] Univ Witwatersrand, Johannesburg, South Africa.
[Klugman, Keith P.] MRC, Natl Inst Communicable Dis, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa.
[Feris Iglesias, Jesus M.] Hosp Infantil Dr Robert Reid Cabral, Santo Domingo, Dominican Rep.
[Mpoudi-Etame, Mireille] NIAID, Henry M Jackson Fdn, Div Acquired Immune Deficiency Syndrome, NIH, Bethesda, MD 20892 USA.
RP Ramakrishnan, M (reprint author), 2123 Cypress St, Philadelphia, PA 19103 USA.
EM meenaramakri@gmail.com
FU GAVI Alliance; Sabin Vaccine Institute
FX Funding support for our Review was made available from the GAVI Alliance
and the Sabin Vaccine Institute. We would like to thank Claire Twose and
Donna Hesson, librarians at Johns Hopkins, for their help in the
searching of published work, finding articles, and providing input at
many points throughout the process. We would also like to thank our data
extractors Joachim Chijide and Lola Dosunmu. Thanks also to Hope Johnson
for providing the databases of published work of the Global Disease
Burden and Global Serotypes projects, to Maria Deloria Knoll and Aaron
Ulland for their constructive feedback on the paper, and to Olufemi
Akinyanju for sharing his expertise and publications. Our Review would
not have been possible without the logistical support of Michelle
Moncrieffe-Foreman at PneumoADIP and Ana Carvalho and Ciro de Quadros at
the Sabin Vaccine Institute.
NR 50
TC 31
Z9 32
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD MAY
PY 2010
VL 10
IS 5
BP 329
EP 337
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 595HA
UT WOS:000277600100014
PM 20417415
ER
PT J
AU Aggarwal, SP
Zinman, L
Simpson, E
McKinley, J
Jackson, KE
Pinto, H
Kaufman, P
Conwit, RA
Schoenfeld, D
Shefner, J
Cudkowicz, M
AF Aggarwal, Swati P.
Zinman, Lorne
Simpson, Elizabeth
McKinley, Jane
Jackson, Katherine E.
Pinto, Hanika
Kaufman, Petra
Conwit, Robin A.
Schoenfeld, David
Shefner, Jeremy
Cudkowicz, Merit
CA NE Canadian Amyotrophic Lateral Sc
TI Safety and efficacy of lithium in combination with riluzole for
treatment of amyotrophic lateral sclerosis: a randomised, double-blind,
placebo-controlled trial
SO LANCET NEUROLOGY
LA English
DT Article
ID FUNCTIONAL RATING-SCALE; CELLS IN-VITRO; REPORT QIDS-SR; DEPRESSIVE
SYMPTOMATOLOGY; NEURONAL DIFFERENTIATION; PSYCHOMETRIC EVALUATION; QUICK
INVENTORY; MOUSE MODEL; ALSFRS-R; AUTOPHAGY
AB Background In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS.
Methods We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0.68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389.
Findings At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0.51). The hazard ratio of reaching the primary endpoint was 1.13 (95% CI 0.61-2.07). The study was stopped at the first interim analysis because criterion for futility was met (p=0.78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0.15 (95% CI -0.43 to 0.73, p=0.61). There were no major safety concerns. Falls (p=0.04) and back pain (p=0.05) were more common in the lithium group than in the placebo group.
Interpretation We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS.
C1 [Aggarwal, Swati P.; Simpson, Elizabeth; Jackson, Katherine E.; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA.
[Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Charlestown, MA 02129 USA.
[Zinman, Lorne; McKinley, Jane; Pinto, Hanika] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Kaufman, Petra; Conwit, Robin A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY USA.
RP Aggarwal, SP (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM spaggarwal@partners.org
FU University of Rochester central pharmacy; National Institute of
Neurological Disorders and Stroke, USA; ALS Association, USA; ALS
Society of Canada, Canada
FX We thank Claudia Moy and Louise Ritz of the National Institute of
Neurological Disorders and Stroke, Lucie Bruijn of the ALS Association,
and Denise Figlewicz of the ALS Society of Canada. We thank the members
of the data and safety monitoring board for their guidance, medical
monitors Carl Leventhal and James Russell, cardiologist Judy Hung, and
drug monitor Francine Vriesendorp, and the patients and carers for their
commitment and time. We also thank Apotex for providing the lithium and
matching placebo at a discounted rate and the University of Rochester
central pharmacy for their support. Granting agencies in the USA (the
National Institute of Neurological Disorders and Stroke and the ALS
Association) and Canada (the ALS Society of Canada) provided funds
outside of the normal grant cycle after peer review from the ALS
Association while awaiting NIH peer review. PK worked on this trial
whilst at Columbia University; her contribution to the trial was not
related to the National Institutes of Neurological Disorders and Stroke.
NR 23
TC 102
Z9 104
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAY
PY 2010
VL 9
IS 5
BP 481
EP 488
DI 10.1016/S1474-4422(10)70068-5
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 592MY
UT WOS:000277384600012
PM 20363190
ER
PT J
AU Jiang, Y
Wang, Y
Wang, B
Yang, D
Yu, K
Yang, X
Liu, F
Jiang, Z
Li, M
AF Jiang, Y.
Wang, Y.
Wang, B.
Yang, D.
Yu, K.
Yang, X.
Liu, F.
Jiang, Z.
Li, M.
TI Antifungal activity of recombinant mouse beta-defensin 3
SO LETTERS IN APPLIED MICROBIOLOGY
LA English
DT Article
DE antibacterial; antifungal; innate immunity; Recombinant mouse
beta-defensin 3
ID SPECTRUM ANTIMICROBIAL ACTIVITY; HUMAN BETA-DEFENSIN-3; INDUCIBLE
PEPTIDE; INFECTION; TRENDS
AB Aims:
To identify the presence of mouse beta-defensin 3 (Mbd3) (the human homologue of beta-defensin 2) in different tissues and to define the antimicrobial properties of recombinant MBD3 (rMBD3) against a panel of human pathogens.
Methods and Results:
Mbd3 gene expression in different mouse tissues before or after lipopolysaccharide (LPS) injection was compared by semi-quantitative RT-PCR. This analysis demonstrated that epithelial and mucosal tissues expressed Mbd3 independent of LPS stimulation. Evaluation of the antimicrobial properties of recombinant rMBD3 was determined by assessing the median inhibition concentration (IC(50)), minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)/minimal fungicidal concentration (MFC) against various human pathogens.
Conclusion:
Mbd3 gene expression by epithelial and mucosal tissues suggested that MBD3 likely plays an early defensive role against microbial infections. This activity was most significant against filamentous fungi.
Significance and Impact of the Study:
The data presented in this report suggested that formulations containing rMBD3 and related molecules could serve to treat fungal and bacterial infections.
C1 [Jiang, Y.; Wang, Y.; Wang, B.; Yu, K.; Yang, X.; Liu, F.; Jiang, Z.; Li, M.] Sichuan Univ, Dept Microbiol, W China Sch Preclin & Forens Med, Chengdu 610041, Peoples R China.
[Jiang, Y.] Guiyang Med Coll, Dept Microbiol, Guiyang 550004, Peoples R China.
[Yang, D.] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Yang, D.] NCI, Mol Immunoregulat Lab, NCI FCRDC, NIH, Frederick, MD 21702 USA.
[Li, M.] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China.
RP Li, M (reprint author), Sichuan Univ, Dept Microbiol, W China Sch Preclin & Forens Med, Chengdu 610041, Peoples R China.
EM lmy3985@sina.com
FU Natural Science Foundation of China [30671964]
FX This work was financially supported by Natural Science Foundation of
China (no. 30671964).
NR 22
TC 8
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0266-8254
J9 LETT APPL MICROBIOL
JI Lett. Appl. Microbiol.
PD MAY
PY 2010
VL 50
IS 5
BP 468
EP 473
DI 10.1111/j.1472-765X.2010.02824.x
PG 6
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 579WB
UT WOS:000276406400005
PM 20337925
ER
PT J
AU Abdou, AM
Gao, X
Cozen, W
Cerhan, JR
Rothman, N
Martin, MP
Davis, S
Schenk, M
Chanock, SJ
Hartge, P
Carrington, M
Wang, SS
AF Abdou, A. M.
Gao, X.
Cozen, W.
Cerhan, J. R.
Rothman, N.
Martin, M. P.
Davis, S.
Schenk, M.
Chanock, S. J.
Hartge, P.
Carrington, M.
Wang, S. S.
TI Human leukocyte antigen (HLA) A1-B8-DR3 (8.1) haplotype, tumor necrosis
factor (TNF) G-308A, and risk of non-Hodgkin lymphoma
SO LEUKEMIA
LA English
DT Letter
ID INTERLYMPH-CONSORTIUM; POLYMORPHISMS; ASSOCIATION
C1 [Abdou, A. M.; Gao, X.; Martin, M. P.; Carrington, M.] NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Div, Frederick, MD 21701 USA.
[Cozen, W.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Cerhan, J. R.] Mayo Clin, Coll Med, Rochester, MN USA.
[Rothman, N.; Hartge, P.; Wang, S. S.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Davis, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Davis, S.] Univ Washington, Seattle, WA 98195 USA.
[Schenk, M.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Schenk, M.] Karmanos Canc Inst, Detroit, MI USA.
[Chanock, S. J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
[Wang, S. S.] City Hope Natl Med Ctr, Duarte, CA USA.
[Wang, S. S.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Etiol, Duarte, CA 91010 USA.
RP Abdou, AM (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Div, Frederick, MD 21701 USA.
EM sowang@coh.org
OI Abdou, Amr/0000-0002-3373-2406; Cerhan, James/0000-0002-7482-178X
FU Intramural NIH HHS [Z01 CP010170-07]; NCI NIH HHS [N01 PC067009, N01
PC067010, N01-PC-67009, N01 PC065064, N01 PC067008, N02-PC-71105, P30
CA033572]
NR 10
TC 16
Z9 16
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2010
VL 24
IS 5
BP 1055
EP 1058
DI 10.1038/leu.2010.17
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 595DS
UT WOS:000277591500020
PM 20147981
ER
PT J
AU Guedez, L
Stetler-Stevenson, WG
AF Guedez, Liliana
Stetler-Stevenson, William G.
TI The prognostic value of TIMP-1 in multiple myeloma
SO LEUKEMIA RESEARCH
LA English
DT Editorial Material
DE Multiple myeloma; TIMP-1
ID TISSUE INHIBITOR; METALLOPROTEINASE-1 TIMP-1; PLASMA; CANCER;
DIFFERENTIATION; LESIONS; CELLS
C1 [Guedez, Liliana; Stetler-Stevenson, William G.] NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Guedez, L (reprint author), NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, 8717 Grovemont Circle,Box 100, Bethesda, MD 20892 USA.
EM guedezl@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808;
NR 25
TC 8
Z9 8
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD MAY
PY 2010
VL 34
IS 5
BP 576
EP 577
DI 10.1016/j.leukres.2009.10.005
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 586WI
UT WOS:000276945300005
PM 19878997
ER
PT J
AU Moody, TW
Switzer, C
Santana-Flores, W
Ridnour, LA
Berna, M
Thill, M
Jensen, RT
Sparatore, A
Del Soldato, P
Yeh, GC
Roberts, DD
Giaccone, G
Wink, DA
AF Moody, Terry W.
Switzer, Christopher
Santana-Flores, Wilmarie
Ridnour, Lisa A.
Berna, Marc
Thill, Michelle
Jensen, Robert T.
Sparatore, Anna
Del Soldato, Piero
Yeh, Grace C.
Roberts, David D.
Giaccone, Giuseppe
Wink, David A.
TI Dithiolethione modified valproate and diclofenac increase E-cadherin
expression and decrease proliferation of non-small cell lung cancer
cells
SO LUNG CANCER
LA English
DT Article
DE S-valproate; S-diclofenac; Lung cancer; PGE(2); E-cadherin
ID GROWTH-FACTOR RECEPTOR; MESENCHYMAL TRANSITION; PROSTAGLANDIN E-2;
CYCLOOXYGENASE-2; INHIBITION; INDUCTION; CELECOXIB; MUTATIONS;
GEFITINIB; ASPIRIN
AB The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 mu g/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 mu g/ml, respectively. Using the MTT assay, 10 mu g/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18 mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and 5-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC. Published by Elsevier Ireland Ltd.
C1 [Moody, Terry W.] NCI, Off Director, Ctr Canc Res, Bethesda, MD 20892 USA.
[Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Berna, Marc; Thill, Michelle; Jensen, Robert T.] NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA.
[Sparatore, Anna] Univ Milan, Ist Chim Famaceut & Tossicol Pietro Pratesi, Milan, Italy.
[Del Soldato, Piero] Sulfidris, Milan, Italy.
[Yeh, Grace C.] NCI, Lab Metab, Frederick, MD 21701 USA.
[Roberts, David D.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Off Director, Ctr Canc Res, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
RI Roberts, David/A-9699-2008; Switzer, Christopher/D-9203-2013; Sparatore,
Anna/J-8634-2015; Giaccone, Giuseppe/E-8297-2017
OI Roberts, David/0000-0002-2481-2981; Sparatore, Anna/0000-0003-2135-2649;
Giaccone, Giuseppe/0000-0002-5023-7562
FU NIDDK, of NIH; NCI, of NIH
FX This research was partially supported by the intramural research funds
of the NIDDK and NCI, of NIH.
NR 43
TC 18
Z9 20
U1 2
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD MAY
PY 2010
VL 68
IS 2
BP 154
EP 160
DI 10.1016/j.lungcan.2009.06.012
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 590MQ
UT WOS:000277231000005
PM 19628293
ER
PT J
AU Zhang, MY
Borges, AR
Ptak, RG
Wang, YP
Dimitrov, AS
Alam, SM
Wieczorek, L
Bouma, P
Fouts, T
Jiang, SB
Polonis, VR
Haynes, BF
Quinnan, GV
Montefiori, DC
Dimitrov, DS
AF Zhang, Mei-Yun
Borges, Andrew Rosa
Ptak, Roger G.
Wang, Yanping
Dimitrov, Antony S.
Alam, S. Munir
Wieczorek, Lindsay
Bouma, Peter
Fouts, Timothy
Jiang, Shibo
Polonis, Victoria R.
Haynes, Barton F.
Quinnan, Gerald V.
Montefiori, David C.
Dimitrov, Dimiter S.
TI Potent and broad neutralizing activity of a single chain antibody
fragment against cell-free and cell-associated HIV-1
SO MABS
LA English
DT Article
DE HIV; AIDS; antibodies; scFv; microbicides; therapeutics; vaccines
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY;
SEXUALLY-TRANSMITTED INFECTIONS; CORECEPTOR BINDING-SITE; ANTIRETROVIRAL
THERAPY; ENVELOPE GLYCOPROTEIN; PASSIVE-IMMUNIZATION; GP120;
MICROBICIDES; PREVENTION
AB Several human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small engineered antibodies can target highly conserved epitopes that are not accessible by full-size antibodies. However, their potency has not been comparatively evaluated with known HIV-1-neutralizing hmAbs against large panels of primary isolates. We report here the inhibitory activity of an engineered single chain antibody fragment (scFv), m9, against several panels of primary HIV-1 isolates from group M (clades A-G) using cell-free and cell-associated virus in cell line-based assays. M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs lgG(1) b12, 2G12, 2F5 and 4E10. It also inhibited cell-to-cell transmission of HIV-1 with higher potency than enfuvirtide (T-20, Fuzeon). M9 competed with a sulfated CCR5 N-terminal peptide for binding to gp120-CD4 complex, suggesting an overlapping epitope with the coreceptor binding site. M9 did not react with phosphatidylserine (PS) and cardiolipin (CL), nor did it react with a panel of autoantigens in an antinuclear autoantibody (ANA) assay. We further found that escape mutants resistant to m9 did not emerge in an immune selection assay. These results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development.
C1 [Zhang, Mei-Yun] Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Pokfulam, Hong Kong, Peoples R China.
[Zhang, Mei-Yun; Wang, Yanping; Dimitrov, Dimiter S.] NCI Frederick, CCRNP, CCR, NIH, Frederick, MD USA.
[Borges, Andrew Rosa; Wieczorek, Lindsay] Henry M Jackson Fdn, Dept Vaccine Res, US Mil HIV Res Program, Rockville, MD USA.
[Dimitrov, Antony S.; Fouts, Timothy] Profectus BioSci Inc, Baltimore, MD USA.
[Wang, Yanping] SAIC Frederick Inc, NCI Frederick, Basic Res Program, Frederick, MD USA.
[Ptak, Roger G.] So Res Inst, Frederick, MD USA.
[Bouma, Peter; Quinnan, Gerald V.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Alam, S. Munir; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Viral Immunol, New York, NY 10021 USA.
[Polonis, Victoria R.] Walter Reed Army Inst Res, Div Retrovirol, US Mil HIV Res Program, Rockville, MD USA.
RP Zhang, MY (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Pokfulam, Hong Kong, Peoples R China.
EM zhangmy@hku.hk
RI Zhang, Mei-Yun/E-9908-2010; Jiang, Shibo/L-4500-2014;
OI Fouts, Timothy/0000-0002-2429-2859
FU The University of Hong Kong; NIH; NIH, National Cancer Institute, Center
for Cancer Research; Gates Foundation; NIH, National Cancer Institute
[NO1-CO-12400]; Southern Research Institute
FX We thank Drs. Robert Blumenthal, Peter Kwong and Michael Fung for their
helpful discussions. We also thank Monogram Biosciences for performing
U87 cell line-based assays, Clay Osterling for performing the
CCR5-dependent cell-to-cell transmission assays, and Ms. Jenny Ng for
help with preparation of the manuscript. This research was supported by
the internal funds from The University of Hong Kong, by the NIH
Intramural AIDS Targeted Antiviral Program (IATAP), the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research, and the Gates Foundation to DSD, by Federal funds from
the NIH, National Cancer Institute, under Contract No. NO1-CO-12400, and
by internal funds from Southern Research Institute. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 47
TC 10
Z9 10
U1 1
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD MAY-JUN
PY 2010
VL 2
IS 3
BP 266
EP 274
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 644OL
UT WOS:000281388200006
PM 20305395
ER
PT J
AU Dimitrov, DS
AF Dimitrov, Dimiter S.
TI Therapeutic antibodies, vaccines and antibodyomes
SO MABS
LA English
DT Article
DE antibodies; therapeutics; vaccines; antibodyome; biologicals
ID HUMAN MONOCLONAL-ANTIBODIES; HIV-1 NEUTRALIZING ANTIBODIES; PROTEIN
THERAPEUTICS; INFLUENZA VACCINES; BREAST-CANCER; IMMUNOGENICITY;
THERAPIES; IDENTIFICATION; VIRUSES; LIBRARY
AB The potential for antibodies to act as "magic bullets" for treatment of human disease was recognized a century ago, but its full realization has began to occur only during the last decade. A key to their current success is the ability to make libraries of antibodies/B cells, isolate a single species, and engineer it to be safe, efficacious and of high quality. Despite this progress, major challenges to the effective prevention, diagnosis and treatment of a vast majority of diseases remain. Limited success in the development of effective vaccines against diseases such as AIDS and cancer reflects our incomplete understanding of how antibodies are generated and function. Only a miniscule number of antibodies are characterized out of the universe of antibodies generated by the immune system. Knowledge of antibodyomes the complete sets of antibodies could help solve these and other challenges.
C1 NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21701 USA.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21701 USA.
EM dimiter.dimitrov@nih.gov
FU NIH NCI CCR; Gates Foundation; NIH
FX I would like to thank members of the group Protein Interactions
especially Weizao Chen, Xiadong Xiao, Emily Streaker and John Owens for
discussions, experiments and help. I also thank my collaborators on the
HIV antibodyome project especially Barton Haynes for his vision and
discussions as well as Robert Blumenthal, Chris Broder, Hana Golding and
Ruth Ruprecht for stimulating discussions. I am especially indebted to
Janice Reichert for helpful comments and suggestions. This study was
supported by the NIH NCI CCR intramural program, Gates Foundation, the
NIH intramural AIDS program (IATAP) and the NIH intramural biodefense
program.
NR 71
TC 52
Z9 53
U1 2
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD MAY-JUN
PY 2010
VL 2
IS 3
BP 347
EP 356
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 644OL
UT WOS:000281388200013
PM 20400863
ER
PT J
AU Adams, DK
Mills, SW
Shank, TM
Mullineaux, LS
AF Adams, D. K.
Mills, S. W.
Shank, T. M.
Mullineaux, L. S.
TI Expanding dispersal studies at hydrothermal vents through species
identification of cryptic larval forms
SO MARINE BIOLOGY
LA English
DT Article
ID EAST PACIFIC RISE; MID-ATLANTIC RIDGE; ARCHAEOGASTROPOD LIMPETS;
COMMUNITY STRUCTURE; RIFTIA-PACHYPTILA; MUSSEL BEDS; IN-SITU; DNA;
PATTERNS; FAMILY
AB The rapid identification of hydrothermal vent-endemic larvae to the species level is a key limitation to understanding the dynamic processes that control the abundance and distribution of fauna in such a patchy and ephemeral environment. Many larval forms collected near vents, even those in groups such as gastropods that often form a morphologically distinct larval shell, have not been identified to species. We present a staged approach that combines morphological and molecular identification to optimize the capability, efficiency, and economy of identifying vent gastropod larvae from the northern East Pacific Rise (NEPR). With this approach, 15 new larval forms can be identified to species. A total of 33 of the 41 gastropod species inhabiting the NEPR, and 26 of the 27 gastropod species known to occur specifically in the 9A degrees 50' N region, can be identified to species. Morphological identification efforts are improved by new protoconch descriptions for Gorgoleptis spiralis, Lepetodrilus pustulosus, Nodopelta subnoda, and Echinopelta fistulosa. Even with these new morphological descriptions, the majority of lepetodrilids and peltospirids require molecular identification. Restriction fragment length polymorphism digests are presented as an economical method for identification of five species of Lepetodrilus and six species of peltospirids. The remaining unidentifiable specimens can be assigned to species by comparison to an expanded database of 18S ribosomal DNA. The broad utility of the staged approach was exemplified by the revelation of species-level variation in daily planktonic samples and the identification and characterization of egg capsules belonging to a conid gastropod Gymnobela sp. A. The improved molecular and morphological capabilities nearly double the number of species amenable to field studies of dispersal and population connectivity.
C1 [Adams, D. K.; Mills, S. W.; Shank, T. M.; Mullineaux, L. S.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.
RP Adams, DK (reprint author), NIDCR, NIH, Bethesda, MD 20982 USA.
EM dadams@whoi.edu
RI Huffstickler, John/H-1745-2011; Adams, Diane/E-7831-2015
OI Adams, Diane/0000-0001-6638-5781
FU Woods Hole Oceanographic Institution Deep Ocean Exploration Institute;
National Science Foundation [OCE-0424953, OCE-9712233, OCE-9619605,
OCE-0327261, OCE-0002458]; National Defense Science and Engineering
Graduate
FX We are grateful to the chief scientists, captains and crews of the R/V
Atlantis, the shipboard scientific support group, and the Alvin group
for their support during multiple collection cruises. We thank Amy
Baco-Taylor, Kate Buckman, Abigail Fusaro, and Robert Jennings for
training and assistance with molecular techniques. Louis Kerr supported
the scanning electron microscopy. Carly Strasser, Stace Beaulieu, Robert
Jennings, Jesus Pineda, and Glenn Flierl contributed to discussions at
various stages of research and manuscript preparation. We thank two
anonymous reviewers for their comments. Funding was provided by as Woods
Hole Oceanographic Institution Deep Ocean Exploration Institute grant to
L. M and S. Beaulieu, National Science Foundation grants OCE-0424953,
OCE-9712233, and OCE-9619605 to L.M, OCE-0327261 to T. S., and
OCE-0002458 to K. Von Damm, and a National Defense Science and
Engineering Graduate fellowship to D. A. The experiments comply with the
current laws of the United States of America.
NR 43
TC 4
Z9 4
U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0025-3162
J9 MAR BIOL
JI Mar. Biol.
PD MAY
PY 2010
VL 157
IS 5
BP 1049
EP 1062
DI 10.1007/s00227-009-1386-8
PG 14
WC Marine & Freshwater Biology
SC Marine & Freshwater Biology
GA 582PM
UT WOS:000276610000012
ER
PT J
AU Patterson, AD
Lanz, C
Gonzalez, FJ
Idle, JR
AF Patterson, Andrew D.
Lanz, Christian
Gonzalez, Frank J.
Idle, Jeffrey R.
TI THE ROLE OF MASS SPECTROMETRY-BASED METABOLOMICS IN MEDICAL
COUNTERMEASURES AGAINST RADIATION
SO MASS SPECTROMETRY REVIEWS
LA English
DT Review
DE biodosimetry; ionizing radiation; metabolomics
ID MS-BASED METABOLOMICS; GENE-EXPRESSION; PRUSSIAN-BLUE;
QUANTITATIVE-DETERMINATION; FERRIC HEXACYANOFERRATE;
LIQUID-CHROMATOGRAPHY; IONIZING-RADIATION; UPLC-MS; IDENTIFICATION;
EXPOSURE
AB Radiation metabolomics can be defined as the global profiling of biological fluids to uncover latent, endogenous small molecules whose concentrations change in a dose response manner following exposure to ionizing radiation. In response to the potential threat of nuclear or radiological terrorism, the Center for High-Throughput Minimally Invasive Radiation Biodosimetry was established to develop field-deployable biodosimeters based, in part, on rapid analysis by mass spectrometry of readily anti easily obtainable biofluids. In this review we briefly summarize radiation biology and key events related to actual and potential nuclear disasters, discuss the important contributions the field of mass spectrometry has made to the field of radiation metabolomics, and summarize current discovery efforts to use mass spectrometry-based metabolomics to identify dose-responsive urinary constituents. and ultimately to build and deploy a noninvasive high-throughput biodosimeter. (C) 2009 Wiley Periodicals, Inc.. Mass Spec Rev 29:503-521, 2010
C1 [Lanz, Christian; Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol & Visceral Res, CH-3010 Bern, Switzerland.
[Patterson, Andrew D.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Idle, JR (reprint author), Univ Bern, Inst Clin Pharmacol & Visceral Res, Murtenstr 35, CH-3010 Bern, Switzerland.
EM jeff.idle@ikp.unibe.ch
RI Patterson, Andrew/G-3852-2012;
OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520
FU NIH (NIAID) [U19 AI067773-02]; National Cancer Institute, Center for
Cancer Research; National Institute of General Medical Sciences; U.S.
Smokeless Tobacco Company
FX Contract grant sponsor: NIH (NIAID); Contract grant number: U19
AI067773-02; Contract grant sponsor: National Cancer Institute,
Intramural Research Program, Center for Cancer Research: Contract grant
sponsor: National Institute of General Medical Sciences (Pharmacology
Research Associate in Training Fellowship): Contract grant sponsor: U.S.
Smokeless Tobacco Company.
NR 92
TC 26
Z9 26
U1 0
U2 14
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0277-7037
J9 MASS SPECTROM REV
JI Mass Spectrom. Rev.
PD MAY-JUN
PY 2010
VL 29
IS 3
BP 503
EP 521
DI 10.1002/mas.20272
PG 19
WC Spectroscopy
SC Spectroscopy
GA 591TB
UT WOS:000277326100005
PM 19890938
ER
PT J
AU von Marschall, Z
Fisher, LW
AF von Marschall, Zofia
Fisher, Larry W.
TI Dentin sialophosphoprotein (DSPP) is cleaved into its two natural dentin
matrix products by three isoforms of bone morphogenetic protein-1 (BMP1)
SO MATRIX BIOLOGY
LA English
DT Article
DE DSPP; DMP1; BMP1; mTLD; PCPE-1; sFRP2
ID PROCOLLAGEN C-PROTEINASE; LINKED GLYCOPROTEINS SIBLINGS; MAMMALIAN
TOLLOID-LIKE; ENHANCER PROTEIN; DENTINOGENESIS IMPERFECTA; MOUSE
FIBROBLASTS; IN-VIVO; OSTEOPONTIN; SIALOPROTEIN; EXPRESSION
AB The protease that cleaves the most abundant non-collagenous protein of dentin matrix, dentin sialophosphoprotein (DSPP), into its two final dentin matrix products, dentin sialoprotein (DSP) and dentin phosphoprotein (DPP), has not been directly identified. In this study, full-length recombinant mouse DSPP was made for the first time in furin-deficient mammalian LoVo cells and used to test the ability of three different isoforms of one candidate protease, bone morphogenetic protein-1 (BMP1) to cleave DSPP at the appropriate site. Furthermore, two reported enhancers of BMP1/mTLD activity (procollagen C-endopeptidase enhancer-1, PCPE-1, and secreted frizzled-related protein-2, sFRP2) were tested for their abilities to modulate BMP1-mediated processing of both DSPP and another SIBLING family member with a similar cleavage motif, dentin matrix protein-1 (DMP1). Three splice variants of BMP1 (classic BMP1, the full-length mTolloid (mTLD), and the shorter isoform lacking the CUB3 domain, BMP1-5) were all shown to cleave the recombinant DSPP in vitro although mTLD was relatively inefficient at processing both DSPP and DMP1. Mutation of the MQGDD peptide motif to IEGDD completely eliminated the ability of all three recombinant isoforms to process full-length recombinant DSPP in vitro thereby verifying the single predicted cleavage site. Furthermore when human bone marrow stromal cells (which naturally express furin-activated BMP1) were transduced with the adenovirus-encoding either wild-type or mutant DSPP, they were observed to fully cleave wild-type DSPP but failed to process the mutant DSPP(MQ Delta IE) during biogenesis. All three BMP1 isoforms were shown to process type I procollagen as well as DSPP and DMP1 much more efficiently in low-salt buffer (<= 50 mM NaCl) compared to commonly used normal saline buffers (150 mM NaCl). Neither PCPE-1 nor sFRP2 were able to enhance any of the three BMP1 isoforms in cleaving either DSPP or DMP1 under either low or normal saline conditions. Interestingly, we were unable to reproduce sFRP2's reported ability to enhance the processing of type I procollagen by BMP1/mTLD. In summary, three isoforms of BMP1 process both DSPP and DMP1 at the MQX/DDP motif, but the identity of a protein that can enhance the cleavage of the two SIBLING proteins remains elusive. Published by Elsevier BM.
C1 [von Marschall, Zofia; Fisher, Larry W.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD USA.
RP Fisher, LW (reprint author), Room 228,Bldg 30,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lfisher@dir.nidcr.nih.gov
FU NIH; DHHS
FX This work was supported by the Division of Intramural Research, NIDCR,
of the Intramural Research Program, NIH, and DHHS.
NR 56
TC 47
Z9 47
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY
PY 2010
VL 29
IS 4
BP 295
EP 303
DI 10.1016/j.matbio.2010.01.002
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 604VR
UT WOS:000278307100007
PM 20079836
ER
PT J
AU Dimitrakakis, C
Tsigginou, A
Keramopoulos, D
Antsaklis, A
AF Dimitrakakis, Constantine
Tsigginou, Alexandra
Keramopoulos, Dimitris
Antsaklis, Aris
TI What have we really learned from 'LIBERATE' trial?
SO MATURITAS
LA English
DT Editorial Material
DE Breast cancer; Tibolone; Recurrence; LIBERATE trial; Menopausal symptoms
ID BREAST-CANCER; POSTMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; DOUBLE-BLIND;
TIBOLONE; RECURRENCE; SURVIVAL; THERAPY
AB LIBERATE trial reports that Tibolone use increases the risk of recurrence in breast cancer patients with vasomotor symptoms. However, there are some uncertainties and weak points in the study. Emerged questions are if interpretation of the results could be extrapolated to all breast cancer patients or there are specific subgroups that could use Tibolone without increasing relapse rate. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Dimitrakakis, Constantine; Tsigginou, Alexandra; Keramopoulos, Dimitris; Antsaklis, Aris] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece.
[Dimitrakakis, Constantine] NICHD, NIH, Bethesda, MD USA.
RP Dimitrakakis, C (reprint author), Univ Athens, Sch Med, Dept Ob Gyn 1, 80 Vas Sophias Ave, Athens 11528, Greece.
EM atsigginou@med.uoa.gr
NR 6
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-5122
J9 MATURITAS
JI Maturitas
PD MAY
PY 2010
VL 66
IS 1
BP 99
EP 100
DI 10.1016/j.maturitas.2010.02.012
PG 2
WC Geriatrics & Gerontology; Obstetrics & Gynecology
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA 599ZN
UT WOS:000277953200017
PM 20236777
ER
PT J
AU Kweon, O
Kim, SJ
Freeman, JP
Song, J
Baek, S
Cerniglia, CE
AF Kweon, Ohgew
Kim, Seong-Jae
Freeman, James P.
Song, Jaekyeong
Baek, Songjoon
Cerniglia, Carl E.
TI Substrate Specificity and Structural Characteristics of the Novel Rieske
Nonheme Iron Aromatic Ring-Hydroxylating Oxygenases NidAB and NidA3B3
from Mycobacterium vanbaalenii PYR-1
SO MBIO
LA English
DT Article
ID SP STRAIN PYR-1; NAPHTHALENE DIOXYGENASE; HYDROCARBON DEGRADATION;
DEGRADING MYCOBACTERIUM; BIPHENYL DIOXYGENASE; PYRENE DEGRADATION;
PSEUDOMONAS-PUTIDA; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; ACTIVE-SITE
AB The Rieske nonheme iron aromatic ring-hydroxylating oxygenases (RHOs) NidAB and NidA3B3 from Mycobacterium vanbaalenii PYR-1 have been implicated in the initial oxidation of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs), forming cis-dihydrodiols. To clarify how these two RHOs are functionally different with respect to the degradation of HMW PAHs, we investigated their substrate specificities to 13 representative aromatic substrates (toluene, m-xylene, phthalate, biphenyl, naphthalene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a] anthracene, benzo[a] pyrene, carbazole, and dibenzothiophene) by enzyme reconstitution studies of Escherichia coli. Both Nid systems were identified to be compatible with type V electron transport chain (ETC) components, consisting of a [3Fe-4S]-type ferredoxin and a glutathione reductase (GR)-type reductase. Metabolite profiles indicated that the Nid systems oxidize a wide range of aromatic hydrocarbon compounds, producing various isomeric dihydrodiol and phenolic compounds. NidAB and NidA3B3 showed the highest conversion rates for pyrene and fluoranthene, respectively, with high product regiospecificity, whereas other aromatic substrates were converted at relatively low regiospecificity. Structural characteristics of the active sites of the Nid systems were investigated and compared to those of other RHOs. The NidAB and NidA3B3 systems showed the largest substrate-binding pockets in the active sites, which satisfies spatial requirements for accepting HMW PAHs. Spatially conserved aromatic amino acids, Phe-Phe-Phe, in the substrate-binding pockets of the Nid systems appeared to play an important role in keeping aromatic substrates within the reactive distance from the iron atom, which allows each oxygen to attack the neighboring carbons.
IMPORTANCE Since the discovery of microbial ring-hydroxylating oxygenases (RHOs) in 1970, the sequences, structures, and enzyme biochemistry, including enantiospecific products, of RHOs have been studied and discussed extensively from the perspective of biodegradation, biotransformation, and biocatalysis processes. However, with all that effort to elucidate the enzymatic mechanisms of RHOs, little is known about the biochemistry and enzymology underlying high-molecular-weight (HMW) polycyclic aromatic hydrocarbon (PAH) degradation. We used Mycobacterium vanbaalenii PYR-1 Nid enzymes, the first type V RHO members to display an apparent substrate preference for HMW PAHs. Here, we examine the mechanism of the RHO reaction by integrating structural information of the NidAB and NidA3B3 enzymes with substrate and product data. This study gives us an understanding of how the model RHO systems of M. vanbaalenii PYR-1 metabolize HMW PAHs. The information obtained would also be helpful for successful application of RHO enzymes to the production of industrially and medically important chiral chemicals and the development of PAH bioremediation technologies.
C1 [Kweon, Ohgew; Kim, Seong-Jae; Song, Jaekyeong; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Freeman, James P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Song, Jaekyeong] Natl Inst Agr Biotechnol, Div Biosafety, Suwon, South Korea.
[Baek, Songjoon] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM carl.cerniglia@fda.hhs.gov
FU National Center for Toxicological Research
FX This work was supported in part by an appointment to the Postgraduate
Research Program at the National Center for Toxicological Research
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of Energy
and the U.S. Food and Drug Administration.
NR 53
TC 12
Z9 13
U1 4
U2 28
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2010
VL 1
IS 2
AR e00135-10
DI 10.1128/mBio.00135-10
PG 11
WC Microbiology
SC Microbiology
GA 686SX
UT WOS:000284717100005
ER
PT J
AU Shoham, S
Magill, SS
Merz, WG
Gonzalez, C
Seibel, N
Buchanan, WL
Knudsen, TA
Sarkisova, TA
Walsh, TJ
AF Shoham, Shmuel
Magill, Shelley S.
Merz, William G.
Gonzalez, Corina
Seibel, Nita
Buchanan, Wendy L.
Knudsen, Tena A.
Sarkisova, Tatyana A.
Walsh, Thomas J.
TI Primary treatment of zygomycosis with liposomal amphotericin B: analysis
of 28 cases
SO MEDICAL MYCOLOGY
LA English
DT Article
DE zygomycosis; liposomal amphotericin B; leukemia; hematopoietic stem cell
transplantation; Rhizopus oryzae
ID CELL TRANSPLANT RECIPIENTS; INVASIVE FUNGAL-INFECTIONS;
COLONY-STIMULATING FACTOR; CARE CANCER CENTER; LIPID COMPLEX; CEREBRAL
MUCORMYCOSIS; ANTIFUNGAL THERAPY; EFFICACY; SAFETY; EPIDEMIOLOGY
AB Lipid formulations of amphotericin B are increasingly used in lieu of deoxycholate amphotericin B for primary treatment of zygomycosis, but little is known about the efficacy of the former antifungal in treating this fungal disease. We therefore undertook an analysis of a case series of all patients with zygomycosis who received L-AMB for primary antifungal therapy in five major mid-Atlantic medical centers. Among the categories of variables studied were demographics, methods of diagnosis, microbiology, sites of infection, global responses, and survival. The median patient age was 44 years and 71% were male. Immunosuppressive hematological disorders (54%) were the most common underlying condition. Pulmonary disease constituted 50% of infections, sinus infection 29%, and cutaneous disease 18%. Members of the genus Rhizopus were the most common recovered agents. Success as defined by complete or partial positive response was noted in 32% of the cases. Concomitant surgery was performed in 46% of the cases, with similar response rates (31%). Overall survival was 39%. L-AMB was effective as primary therapy in only some patients in this cohort of highly immunocompromised individuals with invasive zygomycosis underscoring the importance of host response and the need for further advances for treatment of this lethal infection.
C1 [Buchanan, Wendy L.; Knudsen, Tena A.; Sarkisova, Tatyana A.; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Shoham, Shmuel] Washington Hosp Ctr, Dept Med, Infect Dis Sect, Washington, DC 20010 USA.
[Magill, Shelley S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Magill, Shelley S.; Merz, William G.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Gonzalez, Corina] Georgetown Univ, Med Ctr, Dept Pediat, Div Pediat Hematol Oncol, Washington, DC 20007 USA.
[Seibel, Nita] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
RP Walsh, TJ (reprint author), Natl Canc Inst CRC, Immunocompromised Host Sect, CRC,1W,1-5740,10 Ctr Dr, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
FU National Cancer Institute; Astellas Healthcare Inc.; Astellas Pharma US,
Inc.; Pfizer Inc.; Merck and Co., Inc.; Enzon Inc.
FX This work was supported in part by the intramural program of the
National Cancer Institute and by a grant from Astellas Healthcare Inc.;
Declaration of interest: Dr Shoham has received research support from
Astellas Pharma US, Inc., Pfizer Inc., Merck and Co., Inc., and Enzon
Inc. and honoraria for speaking on behalf of or consulting for: Astellas
Pharma US, Inc., Pfizer Inc., Merck and Co., Inc., Enzon Inc., and
Schering-Plough Corporation.; Dr Magill has received research support
from, and consulted for, Pfizer Inc. and received an honorarium from
Astellas Pharma US, Inc.
NR 36
TC 18
Z9 18
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1369-3786
J9 MED MYCOL
JI Med. Mycol.
PD MAY
PY 2010
VL 48
IS 3
BP 511
EP 517
DI 10.3109/13693780903311944
PG 7
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 579IV
UT WOS:000276363900011
PM 19824881
ER
PT J
AU Schrack, JA
Simonsick, EM
Chaves, PHM
Ferrucci, L
AF Schrack, Jennifer A.
Simonsick, Eleanor M.
Chaves, Paulo H. M.
Ferrucci, Luigi
TI Energy Availability And Walking Speed In Older Adults: A Key To
Mobility?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Schrack, Jennifer A.; Chaves, Paulo H. M.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Simonsick, Eleanor M.; Ferrucci, Luigi] NIH, Baltimore, MD USA.
EM jschrack@jhsph.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 739
BP 48
EP 48
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226300137
ER
PT J
AU Colbert, LH
Matthews, CE
Schoeller, DA
AF Colbert, Lisa H.
Matthews, Charles E.
Schoeller, Dale A.
TI Validity of Physical Activity Measures During a 23-hour Metabolic
Chamber Stay in Older Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Matthews, Charles E.] NCI, NIH, Bethesda, MD 20892 USA.
[Colbert, Lisa H.; Schoeller, Dale A.] Univ Wisconsin, Madison, WI 53706 USA.
EM lhcolbert@education.wisc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 958
BP 116
EP 116
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226300330
ER
PT J
AU Haskell, W
Troiano, R
Ordovas, J
Phillips, M
Hammond, J
Maise, D
Ramos, E
Hamilton, CM
AF Haskell, William
Troiano, Richard
Ordovas, Jose
Phillips, Michael
Hammond, Jane
Maise, Debbie
Ramos, Erin
Hamilton, Carol M.
TI Consensus Measures of Physical Activity and Physical Fitness for
Genome-wide Association Studies
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Haskell, William] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Troiano, Richard] NCI, Bethesda, MD 20892 USA.
[Ordovas, Jose] Tufts Univ, Boston, MA 02111 USA.
[Phillips, Michael; Hammond, Jane; Maise, Debbie; Hamilton, Carol M.] RTI Int, Res Triangle Pk, NC USA.
[Ramos, Erin] NHGRI, Bethesda, MD 20892 USA.
EM whaskell@stanford.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 957
BP 116
EP 116
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226300329
ER
PT J
AU McClain, JJ
Dodd, KW
Berrigan, D
Troiano, RP
AF McClain, James J.
Dodd, Kevin W.
Berrigan, David
Troiano, Richard P.
TI How Many Accelerometer Days are Needed for Stable Population and
Individual Weekly Activity Estimates?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [McClain, James J.; Dodd, Kevin W.; Berrigan, David; Troiano, Richard P.] NCI, NIH, Bethesda, MD 20892 USA.
EM james.mcclain@nih.gov
NR 0
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 961
BP 117
EP 118
PG 2
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226300333
ER
PT J
AU Savage, KJ
McPherron, AC
AF Savage, Kathleen J.
McPherron, Alexandra C.
TI Myostatin Alters Myoblast Proliferation and Primary and Secondary Fiber
Proportions Immediately Before Birth
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Savage, Kathleen J.; McPherron, Alexandra C.] NIH, Bethesda, MD 20892 USA.
EM savagek@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 1142
BP 173
EP 173
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226300487
ER
PT J
AU Rogers, CJ
Hursting, SD
Greiner, JW
Schlom, J
AF Rogers, Connie J.
Hursting, Stephen D.
Greiner, John W.
Schlom, Jeffrey
TI Exercise Improves Innate and Adaptive Immune Responses in Obese Mice
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Rogers, Connie J.; Greiner, John W.; Schlom, Jeffrey] NCI, Bethesda, MD 20892 USA.
[Hursting, Stephen D.] Univ Texas Austin, Austin, TX 78712 USA.
EM rogersco@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 1400
BP 259
EP 259
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226301056
ER
PT J
AU Brown, JC
Huedo-Medina, TB
Pescatello, SM
Ferrer, RA
Johnson, BT
Pescatello, LS
AF Brown, Justin C.
Huedo-Medina, Tania B.
Pescatello, Shannon M.
Ferrer, Rebecca A.
Johnson, Blair T.
Pescatello, Linda S.
TI The Efficacy Of Exercise Interventions On Fatigue Among Cancer
Survivors: A Meta-analysis
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Brown, Justin C.; Huedo-Medina, Tania B.; Johnson, Blair T.; Pescatello, Linda S.] Univ Connecticut, Storrs, CT USA.
[Pescatello, Shannon M.] Western New England Coll, Springfield, MA USA.
[Ferrer, Rebecca A.] NCI, Rockville, MD USA.
EM justin.brown@uconn.edu
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 1414
BP 264
EP 265
PG 2
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226301070
ER
PT J
AU McMahon, GC
Brychta, RJ
Chen, KY
AF McMahon, Gregory C.
Brychta, Robert J.
Chen, Kong Y.
TI Validation Of The Actigraph (GT3X) Inclinometer Function
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [McMahon, Gregory C.; Brychta, Robert J.; Chen, Kong Y.] NIDDK, Bethesda, MD USA.
EM McMahonGC@niddk.nih.gov
NR 0
TC 7
Z9 7
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 2045
BP 489
EP 489
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226301699
ER
PT J
AU Pazan, SE
Gracey, C
Danoff, JV
Paul, S
AF Pazan, Steven E.
Gracey, Chris
Danoff, Jerome V.
Paul, Scott
TI Use Of An In-Shoe Pressure Device To Measure Plantar Pressures While
Cycling With Orthotics
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Pazan, Steven E.; Danoff, Jerome V.] Geroge Washington Univ, Washington, DC USA.
[Gracey, Chris; Paul, Scott] NIH, Bethesda, MD 20892 USA.
EM spazan@gmail.com
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 2241
BP 558
EP 558
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226302043
ER
PT J
AU Chantler, P
Nussbacher, A
Gerstenblith, G
Schulman, SP
Becker, LC
Fleg, JL
Ferrucci, L
Lakatta, EG
Najjar, SS
AF Chantler, Paul
Nussbacher, Amit
Gerstenblith, Gary
Schulman, Steven P.
Becker, Lewis C.
Fleg, Jerome L.
Ferrucci, Luigi
Lakatta, Edward G.
Najjar, Samer S.
TI Attenuating The Age-associated Deficit In Peak Arterial-ventricular
Coupling With Sodium Nitroprusside
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Chantler, Paul; Ferrucci, Luigi; Lakatta, Edward G.; Najjar, Samer S.] NIA, NIH, Baltimore, MD 21224 USA.
[Nussbacher, Amit] Univ Sao Paulo, Sao Paulo, Brazil.
[Gerstenblith, Gary; Schulman, Steven P.; Becker, Lewis C.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 2450
BP 630
EP 630
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226302251
ER
PT J
AU Davis, JM
Murphy, EA
Barrilleaux, TL
McClellan, JL
Hebert, JR
Green, JE
AF Davis, J. Mark
Murphy, E. Angela
Barrilleaux, Traci L.
McClellan, Jamie L.
Hebert, James R.
Green, Jeffery E.
TI Benefits Of Exercise Training On Breast Cancer Progression And
Inflammation In C3(1)SV40Tag Mice
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Davis, J. Mark; Murphy, E. Angela; Barrilleaux, Traci L.; McClellan, Jamie L.; Hebert, James R.] Univ S Carolina, Columbia, SC 29208 USA.
[Green, Jeffery E.] NCI, Bethesda, MD 20892 USA.
EM markd@mailbox.sc.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 2496
BP 646
EP 646
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226302297
ER
PT J
AU Beavers, DP
Troiano, RP
Tooze, JA
AF Beavers, Daniel P.
Troiano, Richard P.
Tooze, Janet A.
TI A Measurement Error Model for Physical Activity Level with Application
to a Physical Activity Questionnaire
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural
World Congress on Exercise is Medicine
CY JUN 05, 2010
CL Baltimore, MD
SP Amer Coll Sports Med
C1 [Beavers, Daniel P.; Tooze, Janet A.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Troiano, Richard P.] Natl Canc Inst, Bethesda, MD USA.
EM dbeavers@wfubmc.edu
RI Beavers, Daniel/G-5338-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
SU 1
MA 2959
BP 809
EP 809
PG 1
WC Sport Sciences
SC Sport Sciences
GA 759FO
UT WOS:000290226302759
ER
PT J
AU Sui, XM
Lee, DC
Matthews, CE
Adams, SA
Hebert, JR
Church, TS
Lee, CD
Blair, SN
AF Sui, Xuemei
Lee, Duck-Chul
Matthews, Charles E.
Adams, Swann A.
Hebert, James R.
Church, Timothy S.
Lee, Chong-Do
Blair, Steven N.
TI Influence of Cardiorespiratory Fitness on Lung Cancer Mortality
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE DEATH FROM LUNG CANCER; PHYSICAL ACTIVITY; SMOKING; PREVENTION;
EPIDEMIOLOGY
ID PHYSICAL-ACTIVITY; NEVER SMOKERS; LEISURE-TIME; FOLLOW-UP; RISK; MEN;
WOMEN; EXERCISE; COHORT; EPIDEMIOLOGY
AB SUI, X., D. LEE, C. E. MATTHEWS, S. A. ADAMS, J. R. HEBERT, T. S. CHURCH, C. LEE, and S. N. BLAIR. Influence of Cardiorespiratory Fitness on Lung Cancer Mortality. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 872-878, 2010. Purpose: Previous studies have suggested that higher levels of physical activity may lower lung cancer risk; however, few prospective studies have evaluated lung cancer mortality in relation to cardiorespiratory fitness (CRF), an objective marker of recent physical activity habits. Methods: Thirty-eight thousand men, aged 20-84 yr, without history of cancer, received a preventive medical examination at the Cooper Clinic in Dallas, Texas, between 1974 and 2002. CRF was quantified as maximal treadmill exercise test duration and was grouped for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%). Results: A total of 232 lung cancer deaths occurred during follow-up (mean = 17 yr). After adjustment for age, examination year, body mass index, smoking, drinking, physical activity, and family history of cancer, hazard ratios (95% confidence intervals) for lung cancer deaths across low, moderate, and high CRF categories were 1.0, 0.48 (0.35-0.67), and 0.43 (0.28- 0.65), respectively. There was an inverse association between CRF and lung cancer mortality in former (P for trend = 0.005) and current smokers (P for trend < 0.001) but not in never smokers (trend P = 0.14). Joint analysis of smoking and fitness status revealed a significant 12-fold higher risk of death in current smokers (hazard ratio = 11.9, 95% confidence interval = 6.0-23.6) with low CRF as compared with never smokers who had high CRF. Conclusions: Although the potential for some residual confounding by smoking could not be eliminated, these data suggest that CRF is inversely associated with lung cancer mortality in men. Continued study of CRF in relation to lung cancer, particularly among smokers, may further our understanding of disease etiology and reveal additional strategies for reducing its burden.
C1 [Sui, Xuemei; Lee, Duck-Chul; Blair, Steven N.] Univ S Carolina, Dept Exercise Sci, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Adams, Swann A.; Hebert, James R.; Blair, Steven N.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Adams, Swann A.; Hebert, James R.] Univ S Carolina, Statewide Canc Prevent & Control Program, Columbia, SC 29208 USA.
[Lee, Chong-Do] Arizona State Univ, Dept Exercise & Wellness, Mesa, AZ USA.
[Church, Timothy S.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
RP Sui, XM (reprint author), 921 Assembly St, Columbia, SC 29210 USA.
EM msui@mailbox.sc.edu
RI Arp Adams, Swann/C-7337-2015; matthews, Charles/E-8073-2015
OI Arp Adams, Swann/0000-0001-5779-6802; matthews,
Charles/0000-0001-8037-3103
FU National Institutes of Health [AG06945, HL62508]; Coca-Cola Company
FX This study was supported by the National Institutes of Health grant nos.
AG06945 and HL62508 and in part supported by an unrestricted research
grant from The Coca-Cola Company. The authors thank the Cooper Clinic
physicians and technicians for collecting the baseline data and the
staff at the Cooper Institute for data entry and data management.
NR 43
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Z9 27
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
BP 872
EP 878
DI 10.1249/MSS.0b013e3181c47b65
PG 7
WC Sport Sciences
SC Sport Sciences
GA 584LD
UT WOS:000276752400005
PM 19996990
ER
PT J
AU Kozey, SL
Staudenmayer, JW
Troiano, RP
Freedson, PS
AF Kozey, Sarah L.
Staudenmayer, John W.
Troiano, Richard P.
Freedson, Patty S.
TI Comparison of the ActiGraph 7164 and the ActiGraph GT1M during
Self-Paced Locomotion
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ACCELEROMETERS; PHYSICAL ACTIVITY; WALKING; ACTIVITY MONITORS
ID LIVING PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; COMPUTER-SCIENCE;
UNITED-STATES; ACCELEROMETER; VALIDITY; PEDOMETER; STEPS
AB KOZEY, S. L., J. W. STAUDENMAYER, R. P. TROIANO, and P. S. FREEDSON. Comparison of the ActiGraph 7164 and the ActiGraph GT1M during Self-Paced Locomotion. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 971-976, 2010. Purpose: This study compared the ActiGraph accelerometer model 7164 (AM1) with the ActiGraph GT1M (AM2) during self-paced locomotion. Methods: Participants (n = 116, aged 18-73 yr, mean body mass index = 26.1 kg.m(-2)) walked at self-selected slow, medium, and fast speeds around an indoor circular hallway (0.47 km). Both activity monitors were attached to a belt secured to the hip and simultaneously collected data in 60-s epochs. To compare differences between monitors, the average difference (bias) in count output and steps output was computed at each speed. Time spent in different activity intensities (light, moderate, and vigorous) based on the cut points of Freedson et al. was compared for each minute. Results: The mean +/- SD walking speed was 0.7 +/- 0.22 m.s(-1) for the slow speed, 1.3 +/- 0.17 m.s(-1) for medium, and 2.1 +/- 0.61 m.s(-1) for fast speeds. Ninety-five percent confidence intervals (95% CI) were used to determine significance. Across all speeds, step output was significantly higher for the AM1 (bias = 19.8%, 95% CI = -23.2% to -16.4%) because of the large differences in step output at slow speed. The count output from AM2 was a significantly higher (2.7%, 95% CI = 0.8%-4.7%) than that from AM1. Overall, 96.1% of the minutes were classified into the same MET intensity category by both monitors. Conclusions: The step output between models was not comparable at slow speeds, and comparisons of step data collected with both models should be interpreted with caution. The count output from AM2 was slightly but significantly higher than that from AM1 during the self-paced locomotion, but this difference did not result in meaningful differences in activity intensity classifications. Thus, data collected with AM1 should be comparable to AM2 across studies for estimating habitual activity
C1 [Kozey, Sarah L.; Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA.
[Staudenmayer, John W.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA.
[Troiano, Richard P.] NCI, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA.
RP Freedson, PS (reprint author), 110 Totman Bldg,30 Eastman Ln, Amherst, MA 01003 USA.
EM psf@kin.umass.edu
OI Keadle, Sarah/0000-0002-9569-9306; Troiano, Richard/0000-0002-6807-989X
FU National Cancer Institute [HHSN 261200700343P]
FX This project was funded by contract no. HHSN 261200700343P from the
National Cancer Institute.
NR 24
TC 55
Z9 55
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2010
VL 42
IS 5
BP 971
EP 976
DI 10.1249/MSS.0b013e3181c29e90
PG 6
WC Sport Sciences
SC Sport Sciences
GA 584LD
UT WOS:000276752400017
PM 19997000
ER
PT J
AU Rauh, MJ
Macera, CA
Trone, DW
Reis, JP
Shaffer, RA
AF Rauh, Mitchell J.
Macera, Caroline A.
Trone, Daniel W.
Reis, Jared P.
Shaffer, Richard A.
TI Selected Static Anatomic Measures Predict Overuse Injuries in Female
Recruits
SO MILITARY MEDICINE
LA English
DT Article
ID ANTERIOR KNEE PAIN; PATELLOFEMORAL PAIN; RISK-FACTORS; STRESS-FRACTURES;
ARMY RECRUITS; RUNNERS; TRAINEES; GENDER; WOMEN; ANGLE
AB This prospective study determined whether selected anatomic measures identified women at increased risk of patellofemoral pain syndrome (PFPS) and shin splints (SS). Ten anatomic measures were performed on 748 women before basic training at the Marine Corps Recruit Depot (MCRD), Parris Island, South Carolina. Recruits were then followed throughout basic training for occurrence of injuries. Logistic regression modeling indicated that a left hip internal rotation range of motion (ROM) <= 25 degrees and >= 46 degrees, a right Q angle >= 20 degrees, and left knee hyperextension ROM >= 6 degrees were positively associated with PFPS. Whereas left dorsiflexion ROM >= 21 degrees was associated with SS, right Q angle >= 20 degrees was inversely associated with SS. These findings suggest that multiple anatomic measures can be used to identify women entering MCRD basic training at risk for PFPS and SS injuries.
C1 [Rauh, Mitchell J.; Macera, Caroline A.; Trone, Daniel W.; Shaffer, Richard A.] USN, Hlth Res Ctr, San Diego, CA 92106 USA.
[Rauh, Mitchell J.; Macera, Caroline A.; Shaffer, Richard A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA.
[Rauh, Mitchell J.; Macera, Caroline A.] Sci Applicat Int Corp, San Diego, CA 92121 USA.
[Rauh, Mitchell J.] Rocky Mt Univ Hlth Profess, Grad Program Orthoped & Sports Phys Therapy, Provo, UT 84606 USA.
[Trone, Daniel W.] Univ Calif San Diego, Joint Doctoral Program Publ Hlth Epidemiol, San Diego, CA 92182 USA.
[Reis, Jared P.] NHLBI, Populat Sci Program, Div Cardiovasc Sci, Rockedge Ctr 2, Bethesda, MD 20892 USA.
RP Rauh, MJ (reprint author), USN, Hlth Res Ctr, 140 Sylvester Rd, San Diego, CA 92106 USA.
FU Department of Defense [60213]; [NHRC.2002.0020]
FX This research has been conducted in compliance with all applicable
federal regulations governing the protection of human subjects in
research protocol NHRC.2002.0020. This work was supported by the
Department of Defense, under work unit no. 60213.
NR 36
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Z9 6
U1 2
U2 4
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
J9 MIL MED
JI Milit. Med.
PD MAY
PY 2010
VL 175
IS 5
BP 329
EP 335
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 598FH
UT WOS:000277819700008
PM 20486504
ER
PT J
AU Patlolla, A
Patlolla, B
Tchounwou, P
AF Patlolla, Anita
Patlolla, Babu
Tchounwou, Paul
TI Evaluation of cell viability, DNA damage, and cell death in normal human
dermal fibroblast cells induced by functionalized multiwalled carbon
nanotube
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Multiwalled carbon nanotubes; Human dermal fibroblast; DNA damage;
Annexin-V; Cytotoxicity
ID HEALTH-RISKS; IN-VITRO; KAPPA-B; CYTOTOXICITY; NANOMATERIALS; TOXICITY;
KERATINOCYTES; DEPENDENCE; FULLERENE; APOPTOSIS
AB Multiwalled carbon nanotubes (MWCNTs) are an example of a carbon-based nanomaterial that has won enormous popularity in nanotechnology. Due to their unusual one-dimensional hollow nanostructure and unique physicochemical properties, they are highly desirable for use within the commercial, environmental, and medical sectors. Despite their wide application, there is a lack of information concerning their impact on human health and the environment. While nanotechnology looms large with commercial promise and potential benefit, an equally large issue is the evaluation of potential effects on humans and other biological systems. Our research is focused on cellular response to purified functionalized MWCNT in normal human dermal fibroblast cells. Three exposure concentrations (40, 200, and 400 mu g/ml) of functionalized MWCNT and control (Tween-80 + 0.9% saline) were used in this study. Following exposure to MWCNT, cytotoxicity, genotoxicity, and apoptosis assays were performed using standard protocols. Our results demonstrated a dose-dependent toxicity with functionalized MWCNT. It was found to be toxic and induced massive loss of cell viability through DNA damage and programmed cell death of all doses compared to control. Our results demonstrate that carbon nanotubes indeed can be very toxic at sufficiently high concentrations from environmental and occupational exposure and that careful monitoring of toxicity studies is essential for risk assessment.
C1 [Patlolla, Anita; Tchounwou, Paul] Jackson State Univ, Ctr Environm Hlth, NIH, Mol Toxicol Res Lab, Jackson, MS USA.
[Patlolla, Babu] Alcorn State Univ, Dept Biol, Alcorn, MS USA.
RP Patlolla, A (reprint author), Jackson State Univ, Ctr Environm Hlth, NIH, Mol Toxicol Res Lab, Jackson, MS USA.
EM anita.k.patlolla@jsums.edu
FU National Institute of Health [2G12RR13459]; Title III-Strengthening HBCU
FX This research was supported in part by a grant from National Institute
of Health (Grant No. 2G12RR13459) through RCMI-Center for Environmental
Health and in part by Title III-Strengthening HBCU at Jackson State
University.
NR 34
TC 47
Z9 48
U1 0
U2 15
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD MAY
PY 2010
VL 338
IS 1-2
BP 225
EP 232
DI 10.1007/s11010-009-0356-2
PG 8
WC Cell Biology
SC Cell Biology
GA 584IP
UT WOS:000276745400024
PM 20016928
ER
PT J
AU Quinn, AM
Allali-Hassani, A
Vedadi, M
Simeonov, A
AF Quinn, Amy M.
Allali-Hassani, Abdellah
Vedadi, Masoud
Simeonov, Anton
TI A chemiluminescence-based method for identification of histone lysine
methyltransferase inhibitors
SO MOLECULAR BIOSYSTEMS
LA English
DT Article
ID ADENOSYLMETHIONINE-DEPENDENT METHYLTRANSFERASES; THROUGHPUT SCREENING
ASSAYS; CATALYTIC MECHANISM; CHEMICAL PROBES; G9A; METHYLATION;
CHROMATIN; IMMUNOASSAY; SU(VAR)3-9
AB Methylation of lysine residues, catalyzed by histone methyltransferase (HMT) enzymes, is one of many modifications of core histone proteins that regulate transcription and chromatin structure. G9a is the predominant HMT in mammalian euchromatin and recent data suggest that it is required to perpetuate a malignant phenotype in cancer cells and is implicated in metastasis, supporting this HMT as a therapeutic target for cancer and other diseases associated with epigenetic regulation. Of the methods currently used to measure methyltransferase activity, many involve a separation step or utilize coupling enzymes complicating implementation and data interpretation. Here we describe a homogeneous assay to measure G9a HMT activity using the chemiluminescence-based Alpha Screen immunoassay technology. Methylation of biotinylated-histone peptide is measured through specific antibody-based detection, in conjunction with streptavidin-coated donor and secondary antibody-coated acceptor beads. The method is particularly well suited for detection of inhibitors acting by the desired histone peptide competitive mechanism and is applicable to testing other HMTs, demonstrated here with the G9a homolog EHMT1, also known as GLP.
C1 [Quinn, Amy M.; Simeonov, Anton] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Allali-Hassani, Abdellah; Vedadi, Masoud] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
RP Simeonov, A (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
EM a.simeono@mail.nih.gov
FU NIH Roadmap for Medical Research; NHGRI, NIH; Canadian Institutes for
Health Research; Canadian Foundation for Innovation, Genome Canada
through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska
Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation
Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.;
Novartis Research Foundation; Swedish Agency for Innovation Systems;
Swedish Foundation for Strategic Research; Wellcome Trust
FX This research was supported in part by the Molecular Libraries
Initiative of the NIH Roadmap for Medical Research and the Intramural
Research Program of NHGRI, NIH. The Structural Genomics Consortium is a
registered charity (number 1097737) that receives funds from the
Canadian Institutes for Health Research, the Canadian Foundation for
Innovation, Genome Canada through the Ontario Genomics Institute,
GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg
Foundation, the Ontario Innovation Trust, the Ontario Ministry for
Research and Innovation, Merck & Co., Inc., the Novartis Research
Foundation, the Swedish Agency for Innovation Systems, the Swedish
Foundation for Strategic Research, and the Wellcome Trust.
NR 26
TC 27
Z9 27
U1 0
U2 8
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1742-206X
J9 MOL BIOSYST
JI Mol. Biosyst.
PD MAY
PY 2010
VL 6
IS 5
BP 782
EP 788
DI 10.1039/b921912a
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 591QC
UT WOS:000277315800003
PM 20567762
ER
PT J
AU Ogawa, M
Kosaka, N
Regino, CAS
Mitsunaga, M
Choyke, PL
Kobayashi, H
AF Ogawa, Mikako
Kosaka, Nobuyuki
Regino, Celeste A. S.
Mitsunaga, Makoto
Choyke, Peter L.
Kobayashi, Hisataka
TI High sensitivity detection of cancer in vivo using a dual-controlled
activation fluorescent imaging probe based on H-dimer formation and pH
activation
SO MOLECULAR BIOSYSTEMS
LA English
DT Article
ID REAL-TIME; MULTICOLOR; AGENTS; CELLS
AB The key to improving the sensitivity of in vivo molecular imaging is to increase the target-to-background signal ratio (TBR). Optical imaging has a distinct advantage over other molecular imaging methods in that the fluorescent signal can be activated at the target thus reducing background signal. Previously, we found that H-dimer formation quenches fluorescence of xanthene fluorophores, and among these, TAMRA had the highest quenching ratio. Another approach to lowering background signal is to employ pH activation based on the photon-induced electron transfer (PeT) theory. We hypothesized that combining these two strategies could lead to greater quenching capacity than was possible with either probe alone. A pH-sensitive fluorophore, pHrodo or TAMRA was conjugated to the cancer targeting molecules, avidin (Av) and trastuzumab (Tra). As expected, both pHrodo and TAMRA formed H-dimers when conjugated to avidin or antibody and the dimerization resulted in efficient fluorescence quenching. In addition, pHrodo conjugated probes showed pH-dependent fluorescence activation. When the probes were used in an in vivo animal model, fluorescence endoscopy with Av-pHrodo depicted tumors with high TBR 1 h and 2 h after injection. Av-TAMRA also visualized tumors 1 h and h after the injection, however. TBR was lower due to the background signal from non-specific binding 1 h after the injection as well as background fluorescence from the unbound agent. Thus, we demonstrate that a dual-controlled activatable optical probe based on the combination of H-dimer formation and pH activation can achieve high TBR at early time points during in vivo molecular imaging.
C1 [Ogawa, Mikako; Kosaka, Nobuyuki; Regino, Celeste A. S.; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ogawa, M (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We thank Drs
Masatoshi Takahashi and Masayuki Nishimura (Shimadzu Scientific
Instruments) for great assistance with the mass spectroscopic analyses
of the fluorescence dyes.
NR 11
TC 27
Z9 27
U1 1
U2 15
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1742-206X
J9 MOL BIOSYST
JI Mol. Biosyst.
PD MAY
PY 2010
VL 6
IS 5
BP 888
EP 893
DI 10.1039/b917876g
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 591QC
UT WOS:000277315800016
PM 20567775
ER
PT J
AU Jordan, JJ
Inga, A
Conway, K
Edmiston, S
Carey, LA
Wu, L
Resnick, MA
AF Jordan, Jennifer J.
Inga, Alberto
Conway, Kathleen
Edmiston, Sharon
Carey, Lisa A.
Wu, Lin
Resnick, Michael A.
TI Altered-Function p53 Missense Mutations Identified in Breast Cancers Can
Have Subtle Effects on Transactivation
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID LI-FRAUMENI-SYNDROME; TP53 GENE-MUTATIONS; MUTANT P53; TUMOR-SUPPRESSOR;
CELL-LINES; NEOADJUVANT TREATMENT; TRANSCRIPTION FACTOR; DNA-BINDING;
EXPRESSION; RESCUE
AB Mutations of the sequence-specific master regulator p53 that alter transactivation function from promoter response elements (RE) could result in changes in the strength of gene activation or spectra of genes regulated. Such mutations in this tumor suppressor might lead to dramatic phenotypic changes and diversification of cell responses to stress. We have determined "functional fingerprints" of sporadic breast cancer-related p53 mutants, many of which are also associated with familial cancer proneness such as the Li-Fraumeni syndrome and germline BRCA1/2 mutant-associated cancers. The ability of p53, wild-type and mutants, to transactivate from 11 human target REs has been assessed at variable expression levels using a cellular, isogenomic yeast model system that allows for the rapid analysis of p53 function using a qualitative and a quantitative reporter. Among 50 missense mutants, 29 were classified as loss of function. The remaining 21 retained transactivation toward at least one RE. At high levels of galactose-induced p53 expression, 12 of 21 mutants that retain transactivation seemed similar to wild-type. When the level of galactose was reduced, transactivation defects could be revealed, suggesting that some breast cancer -related mutants can have subtle changes in transcription. These findings have been compared with clinical data from an ongoing neoadjuvant chemotherapy treatment trial for locally advanced breast tumors. The functional and nonfunctional missense mutations may distinguish tumors in terms of demographics, appearance, and relapse, implying that heterogeneity in the functionality of specific p53 mutations could affect clinical behavior and outcome. Mol Cancer Res; 8(5); 701-16. (C)2010 AACR.
C1 [Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Jordan, Jennifer J.; Resnick, Michael A.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
[Carey, Lisa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
[Conway, Kathleen; Edmiston, Sharon] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Inga, Alberto] Univ Trent, CIBIO, Ctr Integrat Biol, Trento, Italy.
[Wu, Lin] Roche Mol Syst, Pleasanton, CA USA.
RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, 111 Alexander Dr,POB 12233,MD3-01, Res Triangle Pk, NC 27709 USA.
EM Resnick@niehs.nih.gov
FU Department of Defense Breast Cancer Research [BC051212]; Italian
Association for Cancer Research; National Cancer Institute Breast Cancer
Specialized Program [CA58223]; NIH [M01RR00046]; Department of Defense
[17-02-1-0521]; National Institute of Environmental Health Sciences
[Z01-ES065079]
FX Department of Defense Breast Cancer Research Program Predoctoral
Traineeship Award BC051212 (J.J. Jordan), Italian Association for Cancer
Research (A. Inga), National Cancer Institute Breast Cancer Specialized
Program of Research Excellence award CA58223 (University of North
Carolina), NIH grant M01RR00046 (L.A. Carey), Department of Defense
award DAMD 17-02-1-0521 (L.A. Carey), Avon/Partners for Progress grant
(L.A. Carey), and National Institute of Environmental Health Sciences
project Z01-ES065079 (M.A. Resnick).
NR 81
TC 23
Z9 23
U1 0
U2 1
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 MAY
PY 2010
VL 8
IS 5
BP 701
EP 716
DI 10.1158/1541-7786.MCR-09-0442
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 607GM
UT WOS:000278487100007
PM 20407015
ER
PT J
AU Brooks, AD
Jacobsen, KM
Li, WQ
Shanker, A
Sayers, TJ
AF Brooks, Alan D.
Jacobsen, Kristen M.
Li, Wenqing
Shanker, Anil
Sayers, Thomas J.
TI Bortezomib Sensitizes Human Renal Cell Carcinomas to TRAIL Apoptosis
through Increased Activation of Caspase-8 in the Death-Inducing
Signaling Complex
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID PROTEASOME INHIBITOR BORTEZOMIB; PROSTATE-CANCER CELLS; LIGAND TRAIL;
TUMOR-CELL; TNF-ALPHA; KAPPA-B; C-FLIP; RESISTANCE; COMBINATION;
LEUKEMIA
AB Bortezomib (VELCADE) could sensitize certain human renal cell carcinoma (RCC) lines to the apoptotic effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Analysis of seven human RCC showed a clear increase in the sensitivity of four of the RCC to TRAIL cytotoxicity following bortezomib (5-20 nmol/L) treatment, whereas the remaining three remained resistant. Tumor cell death following sensitization had all the features of apoptosis. The enhanced antitumor activity of the bortezomib and TRAIL combination was confirmed in long-term (6 days) cancer cell outgrowth assays. The extent of proteasome inhibition by bortezomib in the various RCC was equivalent. Following bortezomib treatment, neither changes in the intracellular protein levels of various Bcl-2 and IAP family members, nor minor changes in expression of TRAIL receptors (DR4, DR5), correlated well with the sensitization or resistance of RCC to TRAIL-mediated apoptosis. However, enhanced procaspase-8 activation following bortezomib pretreatment and subsequent TRAIL exposure was only observed in the sensitized RCC in both cell extracts and death-inducing signaling complex immunoprecipitates. These data suggest that the molecular basis for bortezomib sensitization of RCC to TRAIL primarily involves early amplification of caspase-8 activity. In the absence of this increased caspase-8 activation, other bortezomib-induced changes are not sufficient to sensitize RCC to TRAIL-mediated apoptosis. Mol Cancer Res; 8(5); 729-38. (C)2010 AACR.
C1 [Brooks, Alan D.; Jacobsen, Kristen M.; Shanker, Anil; Sayers, Thomas J.] NCI, Expt Immunol Lab, Frederick, MD 21702 USA.
[Brooks, Alan D.; Shanker, Anil; Sayers, Thomas J.] Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Li, Wenqing] NCI, Canc & Inflammat Program, Mol Immunoregulat Lab, Frederick, MD 21702 USA.
RP Sayers, TJ (reprint author), NCI, Expt Immunol Lab, Frederick, MD 21702 USA.
EM sayerst@mail.nih.gov
RI Sayers, Thomas/G-4859-2015;
OI Shanker, Anil/0000-0001-6372-3669
FU National Cancer Institute, NIH [NO1-CO-12400, HSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, NIH, under contracts NO1-CO-12400 and
HSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U. S. Government. This Research
was supported (in part) by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH.
NR 36
TC 30
Z9 33
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAY
PY 2010
VL 8
IS 5
BP 729
EP 738
DI 10.1158/1541-7786.MCR-10-0022
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 607GM
UT WOS:000278487100009
PM 20442297
ER
PT J
AU Liu, HF
D'Andrade, P
Fulmer-Smentek, S
Lorenzi, P
Kohn, KW
Weinstein, JN
Pommier, Y
Reinhold, WC
AF Liu, Hongfang
D'Andrade, Petula
Fulmer-Smentek, Stephanie
Lorenzi, Philip
Kohn, Kurt W.
Weinstein, John N.
Pommier, Yves
Reinhold, William C.
TI mRNA and microRNA Expression Profiles of the NCI-60 Integrated with Drug
Activities
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID CANCER-CELL LINES; MOLECULAR PHARMACOLOGY; PANEL; TRANSPORTERS;
MICROARRAY; PROGNOSIS; MECHANISM; DATABASE; DISEASE; OVARIAN
AB As part of the Spotlight on Molecular Profiling series, we present here new profiling studies of mRNA and microRNA expression for the 60 cell lines of the National Cancer Institute (NCI) Developmental Therapeutics program (DTP) drug screen (NCI-60) using the 41,000-probe Agilent Whole Human Genome Oligo Microarray and the 15,000-feature Agilent Human microRNA Microarray V2. The expression levels of similar to 21,000 genes and 723 human microRNAs were measured. These profiling studies include quadruplicate technical replicates for six and eight cell lines for mRNA and microRNA, respectively, and duplicates for the remaining cell lines. The resulting data sets are freely available and searchable online in our CellMiner database. The result indicates high reproducibility for both platforms and an essential biological similarity across the various cell types. The mRNA and microRNA expression levels were integrated with our previously published 1,429-compound database of anticancer activity obtained from the NCI DTP drug screen. Large blocks of both mRNAs and microRNAs were identified with predominately unidirectional correlations to similar to 1,300 drugs, including 121 drugs with known mechanisms of action. The data sets presented here will facilitate the identification of groups of mRNAs, microRNAs, and drugs that potentially affect and interact with one another. Mol Cancer Ther; 9(5); 1080-91. (C) 2010 AACR.
C1 [Liu, Hongfang; Lorenzi, Philip; Kohn, Kurt W.; Weinstein, John N.; Pommier, Yves; Reinhold, William C.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[D'Andrade, Petula; Fulmer-Smentek, Stephanie] Agilent Technol, Santa Clara, CA USA.
[D'Andrade, Petula; Fulmer-Smentek, Stephanie] Agilent Technol, Frederick, MD USA.
[Lorenzi, Philip; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Liu, Hongfang] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Reinhold, WC (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wcr@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research [NO1-CO-12400]
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research under contract no.
NO1-CO-12400.
NR 44
TC 81
Z9 82
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAY
PY 2010
VL 9
IS 5
BP 1080
EP 1091
DI 10.1158/1535-7163.MCT-09-0965
PG 12
WC Oncology
SC Oncology
GA 607GQ
UT WOS:000278487500002
PM 20442302
ER
PT J
AU Turbyville, TJ
Gursel, DB
Tuskan, RG
Walrath, JC
Lipschultz, CA
Lockett, SJ
Wiemer, DF
Beutler, JA
Reilly, KM
AF Turbyville, Thomas J.
Guersel, Demirkan B.
Tuskan, Robert G.
Walrath, Jessica C.
Lipschultz, Claudia A.
Lockett, Stephen J.
Wiemer, David F.
Beutler, John A.
Reilly, Karlyne M.
TI Schweinfurthin A Selectively Inhibits Proliferation and Rho Signaling in
Glioma and Neurofibromatosis Type 1 Tumor Cells in a NF1-GRD-Dependent
Manner
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DEFICIENT SCHWANN-CELLS; MALIGNANT ASTROCYTOMA; NATURAL-PRODUCTS; MOUSE
MODELS; STEM-CELLS; PHASE-II; NF1 LOSS; INACTIVATION; GROWTH;
GLIOBLASTOMA
AB Neurofibromatosis type 1 (NF1) is the most common genetic disease affecting the nervous system. Patients typically develop many tumors over their lifetime, leading to increased morbidity and mortality. The NF1 gene, mutated in NF1, is also commonly mutated in sporadic glioblastoma multiforme (GBM). Because both NF1 and GBM are currently incurable, new therapeutic approaches are clearly needed. Natural products represent an opportunity to develop new therapies, as they have been evolutionarily selected to play targeted roles in organisms. Schweinfurthin A is a prenylated stilbene natural product that has previously shown specific inhibitory activity against brain and hematopoietic tumor lines. We show that patient-derived GBM and NF1 malignant peripheral nerve sheath tumor (MPNST) lines, as well as tumor lines derived from the Nf1-/+;Trp53-/+ (NPcis) mouse model of astrocytoma and MPNST are highly sensitive to inhibition by schweinfurthin A and its synthetic analogs. In contrast, primary mouse astrocytes are resistant to the growth inhibitory effects of schweinfurthin A, suggesting that schweinfurthin A may act specifically on tumor cells. Stable transfection of the GTPase-activating protein related domain of Nf1 into Nf1-/-;Trp53-/- astrocytoma cells confers resistance to schweinfurthin A. In addition, the profound effect of schweinfurthin A on dynamic reorganization of the actin cytoskeleton led us to discover that schweinfurthin A inhibits growth factor-stimulated Rho signaling. In summary, we have identified a class of small molecules that specifically inhibit growth of cells from both central and peripheral nervous system tumors and seem to act on NF1-deficient cells through cytoskeletal reorganization correlating to changes in Rho signaling. Mol Cancer Ther; 9(5); 1234-43. (C) 2010 AACR.
C1 [Guersel, Demirkan B.; Tuskan, Robert G.; Walrath, Jessica C.; Lipschultz, Claudia A.; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Turbyville, Thomas J.; Beutler, John A.] NCI, Mol Targets Dev Program, Frederick, MD 21702 USA.
[Turbyville, Thomas J.; Lockett, Stephen J.] NCI, Opt Microscopy & Image Anal Lab SAIC Frederick, Frederick, MD 21702 USA.
[Wiemer, David F.] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, W 7th St & Ft Detrick,POB B, Frederick, MD 21702 USA.
EM beutler@ncifcrf.gov; kreilly@ncifcrf.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU NIH, National Cancer Institute; National Cancer Institute, NIH
[HHSN261200800001E]; Children's Tumor Foundation [2008A-05-001]
FX Intramural Research Program of the NIH, National Cancer Institute to
K.M. Reilly and J.A. Beutler, and with federal funds from the National
Cancer Institute, NIH, under Contract No. HHSN261200800001E to S.J.
Lockett, as well as an award from the Roy J. Carver Charitable Trust as
a Research Program of Excellence and grant 2008A-05-001 from the
Children's Tumor Foundation to D. F. Wiener.
NR 52
TC 21
Z9 22
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAY
PY 2010
VL 9
IS 5
BP 1234
EP 1243
DI 10.1158/1535-7163.MCT-09-0834
PG 10
WC Oncology
SC Oncology
GA 607GQ
UT WOS:000278487500017
PM 20442305
ER
PT J
AU Holbeck, SL
Collins, JM
Doroshow, JH
AF Holbeck, Susan L.
Collins, Jerry M.
Doroshow, James H.
TI Analysis of Food and Drug Administration-Approved Anticancer Agents in
the NCI60 Panel of Human Tumor Cell Lines
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID CANCER; EXPRESSION; INHIBITORS; SENSITIVITY; DISCOVERY; PATTERNS;
UPDATE; SCREEN; GROWTH
AB Since the early 1990s the Developmental Therapeutics Program of the National Cancer Institute (NCI) has utilized a panel of 60 human tumor cell lines (NCI60) representing 9 tissue types to screen for potential new anticancer agents. To date, about 100,000 compounds and 50,000 natural product extracts have been screened. Early in this program it was discovered that the pattern of growth inhibition in these cell lines was similar for compounds of similar mechanism. The development of the COMPARE algorithm provided a means by which investigators, starting with a compound of interest, could identify other compounds whose pattern of growth inhibition was similar. With extensive molecular characterization of these cell lines, COMPARE and other user-defined algorithms have been used to link patterns of molecular expression and drug sensitivity. We describe here the results of screening current Food and Drug Administration (FDA)-approved anticancer agents in the NCI60 screen, with an emphasis on those agents that target signal transduction. We analyzed results from agents with mechanisms of action presumed to be similar; we also carried out a hierarchical clustering of all of these agents. The addition of data from recently approved anticancer agents will increase the utility of the NCI60 databases to the cancer research community. These data are freely accessible to the public on the DTP website (http://dtp.cancer.gov/). The FDA-approved anticancer agents are themselves available from the NCI as a plated set of compounds for research use. Mol Cancer Ther; 9(5); 1451-60. (C) 2010 AACR.
C1 [Holbeck, Susan L.] NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Informat Technol Branch, Bethesda, MD 20892 USA.
RP Holbeck, SL (reprint author), NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Informat Technol Branch, 6130 Execut Blvd,Room 8014, Bethesda, MD 20892 USA.
EM holbecks@mail.nih.gov
FU National Cancer Institute; National Institutes of Health
FX Grant Support; Federal funds from the National Cancer Institute,
National Institutes of Health.
NR 22
TC 88
Z9 88
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAY
PY 2010
VL 9
IS 5
BP 1451
EP 1460
DI 10.1158/1535-7163.MCT-10-0106
PG 10
WC Oncology
SC Oncology
GA 607GQ
UT WOS:000278487500037
PM 20442306
ER
PT J
AU Kino, T
Jaffe, H
Amin, ND
Chakrabarti, M
Zheng, YL
Chrousos, GP
Pant, HC
AF Kino, Tomoshige
Jaffe, Howard
Amin, Niranjana D.
Chakrabarti, Mayukh
Zheng, Ya-Li
Chrousos, George P.
Pant, Harish C.
TI Cyclin-Dependent Kinase 5 Modulates the Transcriptional Activity of the
Mineralocorticoid Receptor and Regulates Expression of Brain-Derived
Neurotrophic Factor
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID LONG-TERM POTENTIATION; GLUCOCORTICOID-RECEPTOR; ALZHEIMERS-DISEASE;
CLINICAL-IMPLICATIONS; RESPONSE ELEMENT; RAT HIPPOCAMPUS; CDK5; PROTEIN;
MICE; P25
AB Glucocorticoids, major end effectors of the stress response, play an essential role in the homeostasis of the central nervous system (CNS) and contribute to memory consolidation and emotional control through their intracellular receptors, the glucocorticoid and mineralocorticoid receptors. Cyclin-dependent kinase 5 (CDK5), on the other hand, plays important roles in the morphogenesis and functions of the central nervous system, and its aberrant activation has been associated with development of neurodegenerative disorders. We previously reported that CDK5 phosphorylated the glucocorticoid receptor and modulated its transcriptional activity. Here we found that CDK5 also regulated mineralocorticoid receptor-induced transcriptional activity by phosphorylating multiple serine and threonine residues located in its N-terminal domain through physical interaction. Aldosterone and dexamethasone, respectively, increased and suppressed mRNA/protein expression of brain-derived neurotrophic factor (BDNF) in rat cortical neuronal cells, whereas the endogenous glucocorticoid corticosterone showed a biphasic effect. CDK5 enhanced the effect of aldosterone and dexamethasone on BDNF expression. Because this neurotrophic factor plays critical roles in neuronal viability, synaptic plasticity, consolidation of memory, and emotional changes, we suggest that aberrant activation of CDK5 might influence these functions through corticosteroid receptors/BDNF. (Molecular Endocrinology 24: 941-952, 2010)
C1 [Kino, Tomoshige] NINDS, Unit Mol Hormone Act,Program Reprod & Adult Endoc, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH,Clin Res Ctr, Bethesda, MD 20892 USA.
[Jaffe, Howard] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA.
[Amin, Niranjana D.; Zheng, Ya-Li; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Chrousos, George P.] Univ Athens, Dept Pediat 1, Athens 11527, Greece.
RP Kino, T (reprint author), NINDS, Unit Mol Hormone Act,Program Reprod & Adult Endoc, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH,Clin Res Ctr, Bldg 10,Room 1-3140,10 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 Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, MD
FX This work was supported in part by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD.
NR 61
TC 35
Z9 36
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2010
VL 24
IS 5
BP 941
EP 952
DI 10.1210/me.2009-0395
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 588LH
UT WOS:000277071100007
PM 20357208
ER
PT J
AU Li, Y
Birnbaumer, L
Teng, CT
AF Li, Yin
Birnbaumer, Lutz
Teng, Christina T.
TI Regulation of ERR alpha Gene Expression by Estrogen Receptor Agonists
and Antagonists in SKBR3 Breast Cancer Cells: Differential Molecular
Mechanisms Mediated by G Protein-Coupled Receptor GPR30/GPER-1
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; HORMONE RESPONSE ELEMENT; HUMAN LACTOFERRIN
GENE; TRANSCRIPTIONAL ACTIVATION; TYROSINE KINASE; ORPHAN RECEPTOR;
TARGET GENES; GPR30; BETA; PROMOTER
AB In selected tissues and cell lines, 17 beta-estradiol (E2) regulates the expression of estrogen-related receptor alpha (ERR alpha), a member of the orphan nuclear receptor family. This effect is thought to be mediated by the estrogen receptor alpha (ER alpha). However in the ER alpha- and ER beta-negative SKBR3 breast cancer cell line, physiological levels of E2 also stimulate ERR alpha expression. Here, we explored the molecular mechanism that mediates estrogen action in ER-negative breast cancer cells. We observed that E2, the ER alpha agonist, as well as the ER alpha antagonists ICI 182,780 and tamoxifen (TAM), a selective ER modulator, stimulate the transcriptional activity of the ERR alpha gene and increase the production of ERR alpha protein in SKBR3 cells. Moreover, the ERR alpha downstream target genes expression and cellular proliferation are also increased. We show further that the G protein-coupled receptor GPR30/GPER-1 (GPER-1) mediates these effects. The GPER-1 specific ligand G-1 mimics the actions of E2, ICI 182,780, and TAM on ERR alpha expression, and changing the levels of GPER-1 mRNA by overexpression or small interfering RNA knockdown affected the expression of ERR alpha accordingly. Utilizing inhibitors, we delineate a different downstream pathway for ER agonist and ER antagonist-triggered signaling through GPER-1. We also find differential histone acetylation and transcription factor recruitment at distinct nucleosomes of the ERR alpha promoter, depending on whether the cells are activated with E2 or with ER antagonists. These findings provide insight into the molecular mechanisms of GPER-1/ERR alpha-mediated signaling and may be relevant to what happens in breast cancer cells escaping inhibitory control by TAM. (Molecular Endocrinology 24: 969-980, 2010)
C1 [Li, Yin; Teng, Christina T.] NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop E2-01, Res Triangle Pk, NC 27709 USA.
EM teng1@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01-ES-070067, Z01-ES-101643]
FX This work was supported by the Intramural Research Program of National
Institutes of Health and by the National Institute of Environmental
Health Sciences Projects Z01-ES-070067 (to C. T. T.) and Z01-ES-101643
(to L. B.).
NR 63
TC 21
Z9 29
U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2010
VL 24
IS 5
BP 969
EP 980
DI 10.1210/me.2009-0148
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 588LH
UT WOS:000277071100009
PM 20211987
ER
PT J
AU Choi, JH
Velayati, A
Stubblefield, BK
Orr-Urtreger, A
Gan-Or, Z
Tayebi, N
Sidransky, E
AF Choi, Jae Hyuk
Velayati, Arash
Stubblefield, Barbara K.
Orr-Urtreger, Avi
Gan-Or, Ziv
Tayebi, Nahid
Sidransky, Ellen
TI False-positive results using a Gaucher diagnostic kit - RecTL and N370S
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Gaucher disease; Glucocerebrosidase; Molecular diagnostic kit;
Recombinant allele; Parkinson disease; Allele specific oligonucleotides
ID ASHKENAZI JEWISH POPULATION; GLUCOCEREBROSIDASE MUTATIONS; DISEASE
AB The Pronto(R) Gaucher kits and Pronto(R) Gaucher RecTL Amplification Mix, marketed to identify mutations in the gene for glucocerebrosidase, are widely used for the diagnosis of Gaucher disease. Subjects genotyped using this kit have been reported with an allele including both the common N370S mutation and RecTL, a previously described Gaucher mutation arising from recombination between the glucocerebrosidase gene and pseudogene. Using direct sequencing and real-time PCR, we show that the RecTL, N3705 allele is a false positive result, demonstrating possible pitfalls of diagnostic kits. Published by Elsevier Inc.
C1 [Choi, Jae Hyuk; Velayati, Arash; Stubblefield, Barbara K.; Tayebi, Nahid; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Orr-Urtreger, Avi; Gan-Or, Ziv] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel.
[Orr-Urtreger, Avi; Gan-Or, Ziv] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
OI Gan-Or, Ziv/0000-0003-0332-234X
FU National Human Genome Research Institute; National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and National Institutes of
Health.
NR 12
TC 7
Z9 7
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAY
PY 2010
VL 100
IS 1
BP 100
EP 102
DI 10.1016/j.ymgme.2009.12.017
PG 3
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 587IO
UT WOS:000276984700018
PM 20096616
ER
PT J
AU Loken, PR
Magera, MJ
Introne, W
Tortorelli, S
Gavrilov, D
Oglesbee, D
Rinaldo, P
Matern, D
Raymond, K
AF Loken, Perry R.
Magera, Mark J.
Introne, Wendy
Tortorelli, Silvia
Gavrilov, Dimitar
Oglesbee, Devin
Rinaldo, Piero
Matern, Dietrich
Raymond, Kimiyo
TI Homogentisic acid interference in routine urine creatinine determination
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Homogentisic acid; Alkaptonuria; Homogentisate 1,2-dioxygenase; Jaffe
reaction; Creatinine; Interference
ID ASCORBIC-ACID; ALKAPTONURIA; PEROXIDASE
AB We report the artifactual elevation of homogentisic acid (HGA) in urine from alkaptonuric patients after replacing the creatinine method (Jaffe reaction) in our laboratory with an automated enzymatic method. Samples with elevated HGA by GC-MS had lower creatinine values as determined by the enzymatic method than by the Jaffe reaction. The low creatinine values were due to interference by HGA in the enzymatic method. The enzymatic method is unsuitable for creatinine determination in urine of patients with alkaptonuria. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Loken, Perry R.; Magera, Mark J.; Tortorelli, Silvia; Gavrilov, Dimitar; Oglesbee, Devin; Rinaldo, Piero; Matern, Dietrich; Raymond, Kimiyo] Mayo Clin, Coll Med, Biochem Genet Lab, Rochester, MN 55905 USA.
[Introne, Wendy] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Magera, MJ (reprint author), Mayo Clin, Coll Med, Biochem Genet Lab, 200 1st St SW, Rochester, MN 55905 USA.
EM magera.mark@mayo.edu
NR 10
TC 6
Z9 6
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAY
PY 2010
VL 100
IS 1
BP 103
EP 104
DI 10.1016/j.ymgme.2010.01.006
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 587IO
UT WOS:000276984700019
PM 20138792
ER
PT J
AU Huang, KC
Ramamurthi, KS
AF Huang, Kerwyn Casey
Ramamurthi, Kumaran S.
TI Macromolecules that prefer their membranes curvy
SO MOLECULAR MICROBIOLOGY
LA English
DT Review
ID DIVISION PROTEIN DIVIVA; BACILLUS-SUBTILIS; ESCHERICHIA-COLI;
SUBCELLULAR-LOCALIZATION; CELL-DIVISION; SPORE COAT; BACTERIAL-CELL; BAR
DOMAINS; PHOSPHOLIPID-COMPOSITION; POLAR LOCALIZATION
AB P>Understanding the mechanisms that underlie the organization of bacterial cells has become a significant challenge in the field of bacterial cytology. Of specific interest are early macromolecular sorting events that establish cellular non-uniformity and provide chemical landmarks for later localization events. In this review, we will examine specific examples of lipids and proteins that appear to exploit differences in membrane curvature to drive their localization to particular regions of a bacterial cell. We will also discuss the physical limits of curvature-mediated localization within bacteria, and the use of modelling to infer biophysical properties of curvature-sensing macromolecules.
C1 [Huang, Kerwyn Casey] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Huang, KC (reprint author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM kchuang@stanford.edu; ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015
FU National Institutes of Health [K25 GM075000, DP2 OD006466]; NIH National
Cancer Institute Center for Cancer Research
FX We thank members of our labs and Sigolene Lecuyer, Kit Pogliano and Ned
Wingreen for helpful comments. K.H. acknowledges funding from National
Institutes of Health Grants K25 GM075000 and DP2 OD006466. K.R.
acknowledges funding from the Intramural Research Program of the NIH
National Cancer Institute Center for Cancer Research.
NR 80
TC 44
Z9 45
U1 0
U2 26
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD MAY
PY 2010
VL 76
IS 4
BP 822
EP 832
DI 10.1111/j.1365-2958.2010.07168.x
PG 11
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 595JX
UT WOS:000277607600004
PM 20444099
ER
PT J
AU Hartz, AMS
Miller, DS
Bauer, B
AF Hartz, Anika M. S.
Miller, David S.
Bauer, Bjoern
TI Restoring Blood-Brain Barrier P-Glycoprotein Reduces Brain Amyloid-beta
in a Mouse Model of Alzheimer's Disease
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PREGNANE-X-RECEPTOR; UP-REGULATION; XENOBIOTIC RECEPTOR; IN-VIVO;
TRANSPORT; EXPRESSION; MICE; DEPOSITION; PEPTIDE; CLEARANCE
AB Reduced clearance of amyloid-beta (A beta) from brain partly underlies increased A beta brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of A beta from mouse brain capillaries into the vascular space, thus identifying a critical component of the A beta brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type con-trol mice, suggesting a mechanism by which A beta accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16 alpha-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain A beta levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase A beta clearance from the brain and reduce A beta brain accumulation. This mechanism suggests a new therapeutic strategy in AD.
C1 [Bauer, Bjoern] Univ Minnesota, Coll Pharm, Dept Pharmaceut Sci, Duluth, MN 55812 USA.
[Hartz, Anika M. S.] Univ Minnesota, Dept Biochem & Mol Biol, Sch Med, Duluth, MN 55812 USA.
[Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Bauer, B (reprint author), Univ Minnesota, Coll Pharm, Dept Pharmaceut Sci, 1110 Kirby Dr,232 Life Sci, Duluth, MN 55812 USA.
EM bjbauer@d.umn.edu
FU National Institutes of Health National Institute of Environmental Health
Sciences [Z01-ES080048]; Duluth Medical Research Institute; University
of Minnesota College of Pharmacy
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health National Institute of Environmental
Health Sciences [Grant Z01-ES080048]; a Duluth Medical Research
Institute Grant; and University of Minnesota College of Pharmacy startup
funds.
NR 42
TC 118
Z9 125
U1 0
U2 12
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAY
PY 2010
VL 77
IS 5
BP 715
EP 723
DI 10.1124/mol.109.061754
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584VV
UT WOS:000276782500001
PM 20101004
ER
PT J
AU Pillai, AD
Pain, M
Solomon, T
Bokhari, AAB
Desai, SA
AF Pillai, Ajay D.
Pain, Margaret
Solomon, Tsione
Bokhari, Abdullah A. B.
Desai, Sanjay A.
TI A Cell-Based High-Throughput Screen Validates the Plasmodial Surface
Anion Channel As an Antimalarial Target
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID INFECTED HUMAN ERYTHROCYTES; RED-BLOOD-CELLS; MALARIA PARASITE; HOST
ERYTHROCYTE; DRUG DISCOVERY; FALCIPARUM; TRANSPORT; PERMEABILITY;
INHIBITORS; PATHWAYS
AB The plasmodial surface anion channel (PSAC) is an unusual small-conductance ion channel induced on erythrocytes infected with plasmodia, including parasites responsible for human malaria. Although broadly available inhibitors produce microscopic clearance of parasite cultures at high concentrations and suggest that PSAC is an antimalarial target, they have low affinity for the channel and may interfere with other parasite activities. To address these concerns, we developed a miniaturized assay for PSAC activity and carried out a high-throughput inhibitor screen. Approximately 70,000 compounds from synthetic and natural product libraries were screened, revealing inhibitors from multiple structural classes including two novel and potent heterocyclic scaffolds. Single-channel patch-clamp studies indicated that these compounds act directly on PSAC, further implicating a proposed role in transport of diverse solutes. A statistically significant correlation between channel inhibition and in vitro parasite killing by a family of compounds provided chemical validation of PSAC as a drug target. These new inhibitors should be important research tools and may be starting points for much-needed antimalarial drugs.
C1 [Pillai, Ajay D.; Pain, Margaret; Solomon, Tsione; Bokhari, Abdullah A. B.; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM sdesai@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; Medicines for Malaria Venture (MMV)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases and by the Medicines for Malaria Venture (MMV).
NR 39
TC 26
Z9 26
U1 0
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAY
PY 2010
VL 77
IS 5
BP 724
EP 733
DI 10.1124/mol.109.062711
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584VV
UT WOS:000276782500002
PM 20101003
ER
PT J
AU Peng, ZM
Geh, E
Chen, L
Meng, QH
Fan, YX
Sartor, M
Shertzer, HG
Liu, ZG
Puga, A
Xia, Y
AF Peng, Zhimin
Geh, Esmond
Chen, Liang
Meng, Qinghang
Fan, Yunxia
Sartor, Maureen
Shertzer, Howard G.
Liu, Zheng-Gang
Puga, Alvaro
Xia, Ying
TI Inhibitor of kappa B Kinase beta Regulates Redox Homeostasis by
Controlling the Constitutive Levels of Glutathione
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; LIGASE CATALYTIC SUBUNIT;
NECROSIS-FACTOR-ALPHA; REACTIVE OXYGEN; INDUCED APOPTOSIS; OXIDATIVE
STRESS; CELL-DEATH; ACTIVATOR PROTEIN-1; EXPRESSION; TRANSCRIPTION
AB Cytokine-activated inhibitor of kappa B kinase beta (IKK beta) is a key mediator of immune and inflammatory responses, but recent studies suggest that IKK beta is also required for tissue homeostasis in physiopathological processes. Here we report a novel role for IKK beta in maintenance of constitutive levels of the redox scavenger GSH. Inactivation of IKK beta by genetic or pharmacological means results in low cellular GSH content and marked reduction of redox potential. Similar to Ikk beta(-/-) cells, Tnfr1(-/-) and p65(-/-) cells are also GSH-deficient. As a consequence, cells deficient in IKK beta signaling are extremely susceptible to toxicity caused by environmental and pharmacological agents, including oxidants, genotoxic agents, micro-tubule toxins, and arsenic. GSH biosynthesis depends on the activity of the rate-limiting enzyme glutamate-cysteine ligase (GCL), consisting of a catalytic subunit (GCLC) and a modifier subunit (GCLM). We found that loss of IKK beta signaling significantly reduces basal NF-kappa B activity and decreases binding of NF-kappa B to the promoters of Gclc and Gclm, leading to reduction of GCLC and GCLM expression. Conversely, overexpression of GCLC and GCLM in IKK beta-null cells partially restores GSH content and prevents stress-induced cytotoxicity. We suggest that maintenance of GSH is a novel physiological role of the IKK beta-NF-kappa B signaling cascade to prevent oxidative damage and preserve the functional integrity of the cells.
C1 [Xia, Ying] Univ Cincinnati, Coll Med, Dept Environm Hlth, Med Ctr, Cincinnati, OH 45267 USA.
[Peng, Zhimin; Geh, Esmond; Chen, Liang; Meng, Qinghang; Fan, Yunxia; Sartor, Maureen; Shertzer, Howard G.; Puga, Alvaro; Xia, Ying] Univ Cincinnati, Med Ctr, Ctr Environm Genet, Cincinnati, OH 45267 USA.
[Liu, Zheng-Gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Xia, Y (reprint author), Univ Cincinnati, Coll Med, Dept Environm Hlth, Med Ctr, 123 E Shields St, Cincinnati, OH 45267 USA.
EM ying.xia@uc.edu
RI peng, zhimin/B-4536-2010; Chen, Liang/G-2990-2013
FU National Institutes of Health National Institute of Environmental Health
Sciences [ES11798, ES10708, ES06096, T32-ES007250]; National Institutes
of Health National Eye Institute [EY15227]; National Institutes of
Health National Cancer Institute
FX This work was supported in part by the National Institutes of Health
National Institute of Environmental Health Sciences [Grants ES11798,
ES10708, ES06096, T32-ES007250]; by the National Institutes of Health
National Eye Institute [Grant EY15227]; and by Intramural Research
Program of the National Institutes of Health National Cancer Institute.
NR 38
TC 15
Z9 18
U1 0
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAY
PY 2010
VL 77
IS 5
BP 784
EP 792
DI 10.1124/mol.109.061424
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584VV
UT WOS:000276782500008
PM 20159942
ER
PT J
AU Jedema, HP
Gianaros, PJ
Greer, PJ
Kerr, DD
Liu, S
Higley, JD
Suomi, SJ
Olsen, AS
Porter, JN
Lopresti, BJ
Hariri, AR
Bradberry, CW
AF Jedema, H. P.
Gianaros, P. J.
Greer, P. J.
Kerr, D. D.
Liu, S.
Higley, J. D.
Suomi, S. J.
Olsen, A. S.
Porter, J. N.
Lopresti, B. J.
Hariri, A. R.
Bradberry, C. W.
TI Cognitive impact of genetic variation of the serotonin transporter in
primates is associated with differences in brain morphology rather than
serotonin neurotransmission
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE 5-HTTLPR; serotonin transporter; polymorphism; cognition; development;
rhesus macaque
ID ORBITOFRONTAL CORTEX; PROMOTER REGION; 5-HTTLPR POLYMORPHISM; TRYPTOPHAN
DEPLETION; CINGULATE CORTEX; DECISION-MAKING; RHESUS MACAQUES;
CEREBRAL-CORTEX; GENOTYPE; AMYGDALA
AB A powerful convergence of genetics, neuroimaging and epidemiological research has identified the biological pathways mediating individual differences in complex behavioral processes and the related risk for disease. Orthologous genetic variation in non-human primates (NHPs) represents a unique opportunity to characterize the detailed molecular and cellular mechanisms that bias behaviorally and clinically relevant brain function. We report that a rhesus macaque orthologue of a common polymorphism of the serotonin transporter gene (rh5-HTTLPR) has strikingly similar effects on behavior and brain morphology to those in humans. Specifically, the rh5-HTTLPR (S)hort allele broadly affects cognitive choice behavior and brain morphology without observably affecting the 5-hydroxytryptamine (5-HT) transporter or 5-HT1A concentrations in vivo. Collectively, our findings indicate that 5-HTTLPR-associated behavioral effects reflect genotype-dependent biases in cortical development rather than static differences in serotonergic signaling mechanisms. Moreover, these data highlight the vast potential of NHP models in advancing our understanding of human genetic variation affecting behavior and neuropsychiatric disease liability. Molecular Psychiatry (2010) 15, 512-522; doi:10.1038/mp.2009.90; published online 1 September 2009
C1 [Jedema, H. P.; Gianaros, P. J.; Kerr, D. D.; Liu, S.; Hariri, A. R.; Bradberry, C. W.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA.
[Greer, P. J.] Univ Pittsburgh, Dept Biol Struct, Pittsburgh, PA 15261 USA.
[Higley, J. D.] Brigham Young Univ, Dept Psychol & Neurosci, Provo, UT 84602 USA.
[Suomi, S. J.; Lopresti, B. J.] NICHD, Comparat Ethol Lab, Poolesville, MD USA.
[Olsen, A. S.; Porter, J. N.; Bradberry, C. W.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15261 USA.
[Bradberry, C. W.] VA Pittsburgh Hlth Serv, Pittsburgh, PA USA.
RP Bradberry, CW (reprint author), Univ Pittsburgh, Dept Psychiat, 3501 5th Ave, Pittsburgh, PA 15261 USA.
EM bradberrycw@upmc.edu
RI Hariri, Ahmad/D-5761-2011; bradberry, charles/M-2082-2015; Lopresti,
Brian/O-2465-2016
OI bradberry, charles/0000-0003-2630-4144; Lopresti,
Brian/0000-0002-0595-0203
FU NARSAD; NIH/NIAAA [014646]; Office of Research and Development Medical
Research Service, Department of Veterans Affairs
FX We thank Professor Robert E. Ferrell, University of Pittsburgh Graduate
School of Public Health, Department of Human Genetics for genotyping.
This research was supported by a NARSAD Young Investigator Award (HPJ),
NIH/NIAAA 014646 (CWB) and a Merit Award from the Office of Research and
Development Medical Research Service, Department of Veterans Affairs
(CWB).
NR 59
TC 65
Z9 66
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD MAY
PY 2010
VL 15
IS 5
BP 512
EP 522
DI 10.1038/mp.2009.90
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 588OO
UT WOS:000277081800009
PM 19721434
ER
PT J
AU Wohlfert, E
Belkaid, Y
AF Wohlfert, E.
Belkaid, Y.
TI Plasticity of T-reg at infected sites
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID CELL-DIFFERENTIATION; ROR-GAMMA; TGF-BETA; IN-VIVO; RESPONSES; LINEAGE;
FOXP3; INDUCTION
AB Regulatory T cells (T-reg) control an array of immune responses both in the context of various polarized settings as well as in distinct microenvironments. This implies that maintenance of peripheral homeostasis relies on the capacity of T-reg to appropriately adapt to these defined settings while sustaining a regulatory program in the face of inflammation. Adaptation of T-reg is particularly critical in tissues constantly exposed to microbes, such as the gut or the skin, or in the context of exposure to pathogenic microbes. Recent evidence supports the idea that the capacity of T-reg to control defined polarized settings can be associated with the acquisition of specific transcription factors previously associated with effector T-cell lineages. In this review we will discuss how such adaptation of T-reg can have a major role in the control of host-microbe interaction.
C1 [Wohlfert, E.; Belkaid, Y.] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001061-02]
NR 23
TC 24
Z9 24
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2010
VL 3
IS 3
BP 213
EP 215
DI 10.1038/mi.2010.11
PG 3
WC Immunology
SC Immunology
GA 585UE
UT WOS:000276854000003
PM 20237465
ER
PT J
AU Xu, L
Kitani, A
Strober, W
AF Xu, L.
Kitani, A.
Strober, W.
TI Molecular mechanisms regulating TGF-beta-induced Foxp3 expression
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID TRANSCRIPTION FACTOR FOXP3; VERSUS-HOST-DISEASE; T-CELL DEVELOPMENT;
RETINOIC-ACID; DNA METHYLATION; CUTTING EDGE; AIRWAY INFLAMMATION;
DEPENDENT MECHANISM; GENE-EXPRESSION; DENDRITIC CELLS
AB Molecular mechanisms regulating transforming growth factor-beta (TGF-beta) induction of Foxp3 ( forkhead box P3) expression and thus induction of induced regulatory T cells (Tregs) have been the focus of a great deal of study in recent years. It has become clear that this process is influenced by a number of factors as perhaps might be predicted by the fact that there is an overarching need of the immune system to finetune response to environmental antigens. In this review we discuss these mechanisms, with the aim of presenting a broad picture of how the various observations fit together to form an integrated regulatory regime.
C1 [Xu, L.; Kitani, A.; Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
EM wstrober@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000432-27]
NR 59
TC 39
Z9 40
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2010
VL 3
IS 3
BP 230
EP 238
DI 10.1038/mi.2010.7
PG 9
WC Immunology
SC Immunology
GA 585UE
UT WOS:000276854000005
PM 20404810
ER
PT J
AU Jankovic, D
Kugler, DG
Sher, A
AF Jankovic, D.
Kugler, D. G.
Sher, A.
TI IL-10 production by CD4(+) effector T cells: a mechanism for
self-regulation
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID PLASMACYTOID DENDRITIC CELLS; INHIBITS CYTOKINE PRODUCTION;
NATURAL-KILLER-CELLS; IFN-GAMMA PRODUCTION; TOXOPLASMA-GONDII;
VIRUS-INFECTION; CUTTING EDGE; IN-VIVO; HELMINTH INFECTION;
TRYPANOSOMA-CRUZI
AB The development of Th1 lymphocytes is essential for cell-mediated immunity and resistance against intracellular pathogens. However, if left unregulated, the same response can cause serious damage to host tissues and lead to mortality. A number of different paracrine regulatory mechanisms involving distinct myeloid and lymphoid subpopulations have been implicated in controlling excessive secretion of inflammatory cytokines by Th1 cells. Much of this work has focused on interleukin (IL)-10, a cytokine with broad anti-inflammatory properties, one of which is to counteract the function of Th1 lymphocytes. While studying the role of IL-10 in regulating immunopathology during infection with the intracellular parasite Toxoplasma gondii, we discovered that the host-protective IL-10 derives in an autocrine manner from conventional interferon-gamma (IFN-gamma)-producing T-bet(+) Foxp3(neg) Th1 cells. In the following review, we will discuss these findings that support the general concept that production of IL-10 is an important self-regulatory function of CD4(+) T lymphocytes.
C1 [Jankovic, D.; Kugler, D. G.; Sher, A.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM DJankovic@niaid.nih.gov; ASher@niaid.nih.gov
FU NIAID, NIH
FX We are grateful to our colleagues in the Laboratory of Parasitic
Diseases for their contributions to the work summarized in this review
and also thank Drs David Sacks, Giorgio Trinchieri, and Anne O'Garra for
helpful discussions. This study was supported by the Intramural Research
Program of the NIAID, NIH.
NR 92
TC 75
Z9 83
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2010
VL 3
IS 3
BP 239
EP 246
DI 10.1038/mi.2010.8
PG 8
WC Immunology
SC Immunology
GA 585UE
UT WOS:000276854000006
PM 20200511
ER
PT J
AU Saba, E
Grivel, JC
Vanpouille, C
Brichacek, B
Fitzgerald, W
Margolis, L
Lisco, A
AF Saba, E.
Grivel, J-C
Vanpouille, C.
Brichacek, B.
Fitzgerald, W.
Margolis, L.
Lisco, A.
TI HIV-1 sexual transmission: early events of HIV-1 infection of human
cervico-vaginal tissue in an optimized ex vivo model
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE; CD4(+) T-CELLS;
INTRAVAGINAL INOCULATION; DENDRITIC CELLS; TYPE-1; PATHOGENESIS;
LYMPHOCYTES; ACTIVATION; PHENOTYPE
AB Infection and dissemination of human immunodeficiency virus (HIV)-1 through the female body after vaginal intercourse depends on the activation/differentiation status of mucosal CD4 T cells. In this study, we investigated this status and the susceptibility to HIV-1 infection of human cervico-vaginal tissue ex vivo. We found that virtually all T cells are of the effector memory phenotype with broad CC chemokine receptor 5 (CCR5) expression. As it does in vivo, human cervico-vaginal tissue ex vivo preferentially supports the productive infection of R5 HIV-1 rather than that of X4 HIV-1 in spite of the broad expression of CXC chemokine receptor 4 (CXCR4). X4 HIV-1 replicated only in the few tissues that were enriched in CD27(+)CD28(+) effector memory CD4 T cells. Productive infection of R5 HIV-1 occurred preferentially in activated CD38(+) CD4 T cells and was followed by a similar activation of HIV-1-uninfected (bystander) CD4 T cells that may amplify viral infection. These results provide new insights into the dependence of HIV-1 infection and dissemination on the activation/differentiation of cervico-vaginal lymphocytes.
C1 [Saba, E.; Grivel, J-C; Vanpouille, C.; Brichacek, B.; Fitzgerald, W.; Margolis, L.; Lisco, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Sect Intercellular Interact, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Sect Intercellular Interact, NIH, Bethesda, MD USA.
EM margolis@helix.nih.gov; liscoa@mail.nih.gov
FU Eunice Kennedy-Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX We thank the entire staff of the Department of Pathology of Children's
National Medical Center for their generous assistance in obtaining human
tonsillar tissues. We thank Dr Oliver Hartley for a generous gift of
PSC-RANTES, Dr Raymond Schinazi for providing us with lamivudine, and Dr
Barry Alpher for correcting the English style of our paper. 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.
NR 44
TC 66
Z9 68
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2010
VL 3
IS 3
BP 280
EP 290
DI 10.1038/mi.2010.2
PG 11
WC Immunology
SC Immunology
GA 585UE
UT WOS:000276854000010
PM 20147895
ER
PT J
AU Pomeroy, IM
Jordan, EK
Frank, JA
Matthews, PM
Esiri, MM
AF Pomeroy, I. M.
Jordan, E. K.
Frank, J. A.
Matthews, P. M.
Esiri, M. M.
TI Focal and diffuse cortical degenerative changes in a marmoset model of
multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE demyelinating disease; experimental autoimmune encephalomyelitis;
immunocytochemistry; inflammation; multiple sclerosis
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CLINICALLY ISOLATED
SYNDROMES; AXONAL-INJURY; CEREBRAL-CORTEX; LESIONS; DEMYELINATION;
INFLAMMATION; DISABILITY; PATHOLOGY; ATROPHY
AB Background: Degenerative features, such as neuronal, glial, synaptic and axonal loss, have been identified in neocortical and other grey matter structures in patients with multiple sclerosis, but mechanisms for neurodegeneration are unclear. Cortical demyelinating lesions are a potential cause of this degeneration, but the pathological and clinical significance of these lesions is uncertain as they remain difficult to identify and study in vivo. In this study we aimed to describe and quantify cellular and subcellular pathology in the cortex of myelin oligodendrocyte glycoprotein-induced marmoset experimental autoimmune encephalomyelitis using quantitative immunohistochemical methods.
Results: We found evidence of diffuse axonal damage occurring throughout cortical grey matter with evidence for synaptic loss and gliosis and a 13.6% decrease in neuronal size and occurring in deep cortical layers. Evidence of additional axonal damage and a 29.6-36.5% loss of oligodendrocytes was found in demyelinated cortical lesions. Leucocortical lesions also showed neuronal loss of 22.2% and a 15.8% increase in oligodendrocyte size.
Conclusions: The marmoset experimental autoimmune encephalomyelitis model, therefore, shows both focal and generalized neurodegeneration. The generalized changes cannot be directly related to focal lesions, suggesting that they are either a consequence of diffusible inflammatory factors or secondary to remote lesions acting through trans-synaptic or retrograde degeneration.
C1 [Pomeroy, I. M.; Matthews, P. M.; Esiri, M. M.] Univ Oxford, Dept Clin Neurol, Oxford, England.
[Jordan, E. K.; Frank, J. A.] NIH, Frank Lab Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Frank, J. A.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, NIH, Bethesda, MD USA.
RP Pomeroy, IM (reprint author), Royal Hallamshire Hosp, Dept Neurol, Sheffield S10 2RX, S Yorkshire, England.
EM ian.pomeroy@nhs.net
OI Matthews, Paul M/0000-0002-1619-8328
FU National Institutes of Neurological Disorders and Stroke, National
Institutes of Health, USA; UK Multiple Sclerosis Society
FX The authors would like to acknowledge Drs Henry McFarland and Roland
Martin from the National Institutes of Neurological Disorders and
Stroke, National Institutes of Health, USA for support of the EAE
marmoset project. The authors would also like to acknowledge the
generous gift of recombinant MOG protein from Robert Weissert from the
Department of Neurology, University of Tuebingen, Germany. This work was
supported by the UK Multiple Sclerosis Society.
NR 38
TC 12
Z9 12
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD MAY
PY 2010
VL 16
IS 5
BP 537
EP 548
DI 10.1177/1352458509360362
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 598LB
UT WOS:000277837200006
PM 20194580
ER
PT J
AU Demchok, JP
Meletiadis, J
Roilides, E
Walsh, TJ
AF Demchok, Joanne P.
Meletiadis, Joseph
Roilides, Emmanuel
Walsh, Thomas J.
TI Comparative pharmacodynamic interaction analysis of triple combinations
of caspofungin and voriconazole or ravuconazole with subinhibitory
concentrations of amphotericin B against Aspergillus spp.
SO MYCOSES
LA English
DT Article
DE Echinocandins; triazoles; combination therapy; antifungal susceptibility
ID EXPERIMENTAL PULMONARY ASPERGILLOSIS; IN-VITRO; INVASIVE ASPERGILLOSIS;
ANTIFUNGAL THERAPY; ANTAGONISM; EFFICACY; ECHINOCANDIN; FUMIGATUS;
TRIAZOLE; SYNERGY
AB P>Triple combination therapy with an antifungal triazole, echinocandin and amphotericin B (AmB) is used in some centres to treat refractory aspergillosis. The objective of this study was to investigate the effect of subinhibitory concentrations of AmB on the double combinations of caspofungin (CAS) + voriconazole (VOR) or ravuconazole (RAV) against Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Isolates were studied in triplicate against CAS/VOR and CAS/RAV combinations by chequerboard broth microdilution. AmB was added to each double combination at concentrations of 0, 0.1 and 0.2 mu g ml-1. The fractional inhibitory concentration (FIC) index was calculated for the double and triple combinations. Comparative analysis was performed by repeated measures analysis followed by Dunnett's post-test. The double combinations of CAS/RAV and CAS/VOR were synergistic or additive in most conditions. Addition of AmB to the double combinations resulted in increased FIC indices for A. fumigatus and A. flavus. By contrast, AmB increased the synergism of the double combinations decreasing FIC indices for A. terreus (P < 0.05). RAV and VOR displayed similar synergistic activity with CAS. The addition of sub-inhibitory amphotericin B concentrations reduced but did not eliminate the synergistic interaction between the echinocandin and triazole against A. fumigatus and A. flavus, while it increased the synergy against A. terreus.
C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Roilides, Emmanuel] Aristotle Univ Thessaloniki, Dept Pediat, GR-54006 Thessaloniki, Greece.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg CRC,1-5750,10 Ctr Dr, Bethesda, MD 20892 USA.
EM peterjo@mail.nih.gov
NR 21
TC 9
Z9 9
U1 1
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0933-7407
J9 MYCOSES
JI Mycoses
PD MAY
PY 2010
VL 53
IS 3
BP 239
EP 245
DI 10.1111/j.1439-0507.2009.01700.x
PG 7
WC Dermatology; Mycology
SC Dermatology; Mycology
GA 580RK
UT WOS:000276467000010
PM 19389068
ER
PT J
AU Munroe, DJ
Harris, TJR
AF Munroe, David J.
Harris, Timothy J. R.
TI Third-generation sequencing fireworks at Marco Island
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
ID POLYMERASE MOLECULES; REAL-TIME; SINGLE
C1 [Munroe, David J.; Harris, Timothy J. R.] SAIC Frederick Inc, Adv Technol Program, NCI, Frederick, MD 21701 USA.
RP Munroe, DJ (reprint author), SAIC Frederick Inc, Adv Technol Program, NCI, Frederick, MD 21701 USA.
EM dmunroe@ncifcrf.gov
FU PHS HHS [HHSN261200800001E]
NR 8
TC 32
Z9 37
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD MAY
PY 2010
VL 28
IS 5
BP 426
EP 428
DI 10.1038/nbt0510-426
PG 3
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 593KG
UT WOS:000277452700018
PM 20458306
ER
PT J
AU Dieterle, F
Sistare, F
Goodsaid, F
Papaluca, M
Ozer, JS
Webb, CP
Baer, W
Senagore, A
Schipper, MJ
Vonderscher, J
Sultana, S
Gerhold, DL
Phillips, JA
Maurer, G
Carl, K
Laurie, D
Harpur, E
Sonee, M
Ennulat, D
Holder, D
Andrews-Cleavenger, D
Gu, YZ
Thompson, KL
Goering, PL
Vidal, JM
Abadie, E
Maciulaitis, R
Jacobson-Kram, D
Defelice, AF
Hausner, EA
Blank, M
Thompson, A
Harlow, P
Throckmorton, D
Xiao, S
Xu, N
Taylor, W
Vamvakas, S
Flamion, B
Lima, BS
Kasper, P
Pasanen, M
Prasad, K
Troth, S
Bounous, D
Robinson-Gravatt, D
Betton, G
Davis, MA
Akunda, J
McDuffie, JE
Suter, L
Obert, L
Guffroy, M
Pinches, M
Jayadev, S
Blomme, EA
Beushausen, SA
Barlow, VG
Collins, N
Waring, J
Honor, D
Snook, S
Lee, JH
Rossi, P
Walker, E
Mattes, W
AF Dieterle, Frank
Sistare, Frank
Goodsaid, Federico
Papaluca, Marisa
Ozer, Josef S.
Webb, Craig P.
Baer, William
Senagore, Anthony
Schipper, Matthew J.
Vonderscher, Jacky
Sultana, Stefan
Gerhold, David L.
Phillips, Jonathan A.
Maurer, Gerard
Carl, Kevin
Laurie, David
Harpur, Ernie
Sonee, Manisha
Ennulat, Daniela
Holder, Dan
Andrews-Cleavenger, Dina
Gu, Yi-Zhong
Thompson, Karol L.
Goering, Peter L.
Vidal, Jean-Marc
Abadie, Eric
Maciulaitis, Romaldas
Jacobson-Kram, David
Defelice, Albert F.
Hausner, Elizabeth A.
Blank, Melanie
Thompson, Aliza
Harlow, Patricia
Throckmorton, Douglas
Xiao, Shen
Xu, Nancy
Taylor, William
Vamvakas, Spiros
Flamion, Bruno
Lima, Beatriz Silva
Kasper, Peter
Pasanen, Markku
Prasad, Krishna
Troth, Sean
Bounous, Denise
Robinson-Gravatt, Denise
Betton, Graham
Davis, Myrtle A.
Akunda, Jackie
McDuffie, James Eric
Suter, Laura
Obert, Leslie
Guffroy, Magalie
Pinches, Mark
Jayadev, Supriya
Blomme, Eric A.
Beushausen, Sven A.
Barlow, Valerie G.
Collins, Nathaniel
Waring, Jeff
Honor, David
Snook, Sandra
Lee, Jinhe
Rossi, Phil
Walker, Elizabeth
Mattes, William
TI Renal biomarker qualification submission: a dialog between the FDA-EMEA
and Predictive Safety Testing Consortium
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID DISEASE
AB The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.
C1 [Dieterle, Frank; Maurer, Gerard; Carl, Kevin; Laurie, David] Novartis Pharma AG, Basel, Switzerland.
[Sistare, Frank; Ozer, Josef S.; Gerhold, David L.] Merck Res Labs, Dept Invest Lab Sci, West Point, PA USA.
[Goodsaid, Federico; Thompson, Karol L.; Goering, Peter L.; Jacobson-Kram, David; Defelice, Albert F.; Hausner, Elizabeth A.; Blank, Melanie; Thompson, Aliza; Harlow, Patricia; Throckmorton, Douglas; Xiao, Shen; Xu, Nancy; Taylor, William] US FDA, Silver Spring, MD USA.
[Papaluca, Marisa; Vidal, Jean-Marc; Abadie, Eric; Maciulaitis, Romaldas; Vamvakas, Spiros; Flamion, Bruno; Lima, Beatriz Silva; Kasper, Peter; Pasanen, Markku; Prasad, Krishna] European Med Agcy, London, England.
[Webb, Craig P.; Baer, William; Senagore, Anthony; Schipper, Matthew J.; Sultana, Stefan] ClinXus, Grand Rapids, MI USA.
[Webb, Craig P.] Van Andel Res Inst, Grand Rapids, MI USA.
[Baer, William] Grand Valley Med Specialists, Grand Rapids, MI USA.
[Senagore, Anthony] Spectrum Hlth, Grand Rapids, MI USA.
[Schipper, Matthew J.] Innovat Analyt Inc, Kalamazoo, MI USA.
[Vonderscher, Jacky; Suter, Laura] Hoffmann La Roche AG, Basel, Switzerland.
[Phillips, Jonathan A.; Jayadev, Supriya] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
[Harpur, Ernie; Guffroy, Magalie; Barlow, Valerie G.] Sanofi Aventis, Malvern, PA USA.
[Sonee, Manisha; McDuffie, James Eric; Snook, Sandra] Johnson & Johnson, San Diego, CA USA.
[Ennulat, Daniela] GlaxoSmith, King Of Prussia, PA USA.
[Holder, Dan] Merck Res Labs, Dept Biometr, West Point, PA USA.
[Andrews-Cleavenger, Dina] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Gu, Yi-Zhong; Collins, Nathaniel] Schering Plough Res Inst, Summit, NJ USA.
[Maciulaitis, Romaldas] Kaunas Med Univ, Dept Basic & Clin Pharmacol, Nephrol Clin Kaunas Med Univ Clin, Kaunas, Lithuania.
[Maciulaitis, Romaldas] State Med Control Agcy, Kaunas, Lithuania.
[Pasanen, Markku] Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland.
[Troth, Sean] Merck Res Labs, Dept Pathol, West Point, PA USA.
[Bounous, Denise] Bristol Myers Squibb Co, Princeton, NJ USA.
[Robinson-Gravatt, Denise; Obert, Leslie; Beushausen, Sven A.] Pfizer Inc, Groton, CT 06340 USA.
[Betton, Graham; Pinches, Mark] AstraZeneca, Macclesfield, Cheshire, England.
[Davis, Myrtle A.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Akunda, Jackie] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Blomme, Eric A.; Waring, Jeff; Honor, David; Lee, Jinhe] Abbott Labs, Abbott Pk, IL 60064 USA.
[Rossi, Phil; Walker, Elizabeth; Mattes, William] Crit Path Inst, Tucson, AZ USA.
RP Dieterle, F (reprint author), Novartis Pharma AG, Basel, Switzerland.
EM frank.dieterle@novartis.com
RI Webb, Craig/I-8123-2012; Silva Lima, Beatriz/A-4284-2014; iMed.ULisboa,
iMed.ULisboa/C-6292-2014; iMed.ULisboa, PharmRegSci /B-5723-2014
OI Silva Lima, Beatriz/0000-0003-0910-7245; iMed.ULisboa, PharmRegSci
/0000-0003-0910-7245
NR 12
TC 171
Z9 178
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD MAY
PY 2010
VL 28
IS 5
BP 455
EP 462
DI 10.1038/nbt.1625
PG 8
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 593KG
UT WOS:000277452700025
PM 20458315
ER
PT J
AU Chambers, JC
Zhang, WH
Lord, GM
van der Harst, P
Lawlor, DA
Sehmi, JS
Gale, DP
Wass, MN
Ahmadi, KR
Bakker, SJL
Beckmann, J
Bilo, HJG
Bochud, M
Brown, MJ
Caulfield, MJ
Connell, JMC
Cook, HT
Cotlarciuc, I
Smith, GD
de Silva, R
Deng, GH
Devuyst, O
Dikkeschei, LD
Dimkovic, N
Dockrell, M
Dominiczak, A
Ebrahim, S
Eggermann, T
Farrall, M
Ferrucci, L
Floege, J
Forouhi, NG
Gansevoort, RT
Han, XJ
Hedblad, B
van der Heide, JJH
Hepkema, BG
Hernandez-Fuentes, M
Hypponen, E
Johnson, T
de Jong, PE
Kleefstra, N
Lagou, V
Lapsley, M
Li, Y
Loos, RJF
Luan, J
Luttropp, K
Marechal, C
Melander, O
Munroe, PB
Nordfors, L
Parsa, A
Peltonen, L
Penninx, BW
Perucha, E
Pouta, A
Prokopenko, I
Roderick, PJ
Ruokonen, A
Samani, NJ
Sanna, S
Schalling, M
Schlessinger, D
Schlieper, G
Seelen, MAJ
Shuldiner, AR
Sjogren, M
Smit, JH
Snieder, H
Soranzo, N
Spector, TD
Stenvinkel, P
Sternberg, MJE
Swaminathan, R
Tanaka, T
Ubink-Veltmaat, LJ
Uda, M
Vollenweider, P
Wallace, C
Waterworth, D
Zerres, K
Waeber, G
Wareham, NJ
Maxwell, PH
McCarthy, MI
Jarvelin, MR
Mooser, V
Abecasis, GR
Lightstone, L
Scott, J
Navis, G
Elliott, P
Kooner, JS
AF Chambers, John C.
Zhang, Weihua
Lord, Graham M.
van der Harst, Pim
Lawlor, Debbie A.
Sehmi, Joban S.
Gale, Daniel P.
Wass, Mark N.
Ahmadi, Kourosh R.
Bakker, Stephan J. L.
Beckmann, Jacqui
Bilo, Henk J. G.
Bochud, Murielle
Brown, Morris J.
Caulfield, Mark J.
Connell, John M. C.
Cook, H. Terence
Cotlarciuc, Ioana
Smith, George Davey
de Silva, Ranil
Deng, Guohong
Devuyst, Olivier
Dikkeschei, Lambert D.
Dimkovic, Nada
Dockrell, Mark
Dominiczak, Anna
Ebrahim, Shah
Eggermann, Thomas
Farrall, Martin
Ferrucci, Luigi
Floege, Jurgen
Forouhi, Nita G.
Gansevoort, Ron T.
Han, Xijin
Hedblad, Bo
van der Heide, Jaap J. Homan
Hepkema, Bouke G.
Hernandez-Fuentes, Maria
Hypponen, Elina
Johnson, Toby
de Jong, Paul E.
Kleefstra, Nanne
Lagou, Vasiliki
Lapsley, Marta
Li, Yun
Loos, Ruth J. F.
Luan, Jian'an
Luttropp, Karin
Marechal, Celine
Melander, Olle
Munroe, Patricia B.
Nordfors, Louise
Parsa, Afshin
Peltonen, Leena
Penninx, Brenda W.
Perucha, Esperanza
Pouta, Anneli
Prokopenko, Inga
Roderick, Paul J.
Ruokonen, Aimo
Samani, Nilesh J.
Sanna, Serena
Schalling, Martin
Schlessinger, David
Schlieper, Georg
Seelen, Marc A. J.
Shuldiner, Alan R.
Sjogren, Marketa
Smit, Johannes H.
Snieder, Harold
Soranzo, Nicole
Spector, Timothy D.
Stenvinkel, Peter
Sternberg, Michael J. E.
Swaminathan, Ramasamyiyer
Tanaka, Toshiko
Ubink-Veltmaat, Lielith J.
Uda, Manuela
Vollenweider, Peter
Wallace, Chris
Waterworth, Dawn
Zerres, Klaus
Waeber, Gerard
Wareham, Nicholas J.
Maxwell, Patrick H.
McCarthy, Mark I.
Jarvelin, Marjo-Riitta
Mooser, Vincent
Abecasis, Goncalo R.
Lightstone, Liz
Scott, James
Navis, Gerjan
Elliott, Paul
Kooner, Jaspal S.
TI Genetic loci influencing kidney function and chronic kidney disease
SO NATURE GENETICS
LA English
DT Article
ID OCT2
AB Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
C1 [Chambers, John C.; Zhang, Weihua; Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Chambers, John C.; Zhang, Weihua; Sehmi, Joban S.; de Silva, Ranil; Kooner, Jaspal S.] Ealing Hosp Natl Hlth Serv NHS Trust, Middlesex, England.
[Lord, Graham M.; Hernandez-Fuentes, Maria; Perucha, Esperanza] Kings Coll London, Dept Nephrol & Transplantat, London, England.
[Lord, Graham M.; Hernandez-Fuentes, Maria; Perucha, Esperanza] Kings Coll London, MRC, London, England.
[Lord, Graham M.; Hernandez-Fuentes, Maria; Perucha, Esperanza] Guys & St Thomas NHS Fdn Trust, Natl Inst Hlth Res, Comprehens Biomed Res Ctr, London, England.
[Sehmi, Joban S.; de Silva, Ranil; Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Lawlor, Debbie A.; Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Gale, Daniel P.; Maxwell, Patrick H.] UCL, Div Med, London, England.
[Wass, Mark N.; Sternberg, Michael J. E.] Univ London Imperial Coll Sci Technol & Med, Struct Bioinformat Grp, London, England.
[Ahmadi, Kourosh R.; Cotlarciuc, Ioana; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Twin Res & Genet Epidemiol Dept, London WC2R 2LS, England.
[Beckmann, Jacqui] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland.
[Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Caulfield, Mark J.; Munroe, Patricia B.] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Genome Ctr, London, England.
[Connell, John M. C.; Dominiczak, Anna] Univ Glasgow, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Cook, H. Terence] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Histopathol, London, England.
[Deng, Guohong] Univ London Imperial Coll Sci Technol & Med, Dept Gastroenterol & Hepatol, London, England.
[Devuyst, Olivier; Marechal, Celine] Catholic Univ Louvain, Sch Med, Div Nephrol, B-1200 Brussels, Belgium.
[Dikkeschei, Lambert D.] Isala Clin, Zwolle, Netherlands.
[Dimkovic, Nada] Zvezdara Univ, Med Ctr, Ctr Renal Dis, Belgrade, Serbia.
[Dockrell, Mark; Lapsley, Marta] Epsom & St Helier Univ Hosp NHS Trust, SW Thames Inst Renal Res, Carshalton, Surrey, England.
[Eggermann, Thomas; Zerres, Klaus] Rheinisch Westfael Tech Hsch Univ Hosp Aachen, Dept Human Genet, Aachen, Germany.
[Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England.
[Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Ferrucci, Luigi; Tanaka, Toshiko] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Floege, Jurgen; Schlieper, Georg] RWTH Univ Hosp Aachen, Dept Nephrol & Clin Immunol, Aachen, Germany.
[Forouhi, Nita G.; Loos, Ruth J. F.; Luan, Jian'an; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Gansevoort, Ron T.; Seelen, Marc A. J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Han, Xijin; Li, Yun; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Hedblad, Bo; Melander, Olle; Sjogren, Marketa] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[van der Heide, Jaap J. Homan] Univ Med Ctr Groningen, Dept Nephrol, NL-9713 AV Groningen, Netherlands.
[Hepkema, Bouke G.] Univ Med Ctr Groningen, Dept Transplantat Immunol, NL-9713 AV Groningen, Netherlands.
[Hypponen, Elina] UCL, Inst Child Hlth, Ctr Epidemiol Child Hlth, London, England.
[Johnson, Toby] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Johnson, Toby] Swiss Inst Bioinformat, Lausanne, Switzerland.
[de Jong, Paul E.; Kleefstra, Nanne] Langerhans Med Res Grp, Zwolle, Netherlands.
[Lagou, Vasiliki; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands.
[Luttropp, Karin; Nordfors, Louise] Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
[Parsa, Afshin] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
[Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England.
[Peltonen, Leena] Biomedicum Helsinki 2U, Nord European Mol Biol Lab EMBL Partnership Mol M, Inst Mol Med Finland, Helsinki, Finland.
[Peltonen, Leena] Univ Helsinki, Helsinki, Finland.
[Peltonen, Leena; Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Helsinki, Finland.
[Penninx, Brenda W.; Smit, Johannes H.] Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med EMGO, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W.; Smit, Johannes H.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Penninx, Brenda W.; Smit, Johannes H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Prokopenko, Inga; McCarthy, Mark I.] Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Prokopenko, Inga; McCarthy, Mark I.] Oxford NIHR Biomed Res Ctr, Oxford, England.
[Roderick, Paul J.] Univ Southampton, Southampton, Hants, England.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, Inst Clin Med, Oulu, Finland.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Leicester, Leics, England.
[Sanna, Serena; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Schalling, Martin] Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
[Schlessinger, David] NIA, Genet Lab, US Natl Inst Hlth Biomed Res Ctr, Baltimore, MD 21224 USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Stenvinkel, Peter] Karolinska Univ Hosp Huddinge, Div Renal Med K56, Stockholm, Sweden.
[Swaminathan, Ramasamyiyer] Guys & St Thomas Hosp Trust, London, England.
[Vollenweider, Peter; Waeber, Gerard] Univ Lausanne, Univ Hosp Ctr, Dept Internal Med, Lausanne, Switzerland.
[Wallace, Chris] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England.
[Waterworth, Dawn; Mooser, Vincent] GlaxoSmithKline, Clin Pharmacol & Discovery Med, Med Genet, King Of Prussia, PA USA.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Lightstone, Liz] Univ London Imperial Coll Sci Technol & Med, Div Med, Renal Sect, London, England.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, HPA Ctr Environm & Hlth,MRC, London, England.
RP Chambers, JC (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
EM john.chambers@ic.ac.uk; j.kooner@imperial.ac.uk
RI Wass, Mark/F-5540-2010; Colaus, PsyColaus/K-6607-2013; Lagou,
Vasiliki/N-8451-2013; Hypponen, Elina/B-2596-2014; Schalling,
Martin/F-1518-2015; Eggermann, Thomas/F-3807-2014; Abecasis,
Goncalo/B-7840-2010; Bochud, Murielle/A-3981-2010; Lord,
Graham/B-3797-2011; Beckmann, Jacques S /A-9772-2008; Spector,
Tim/F-6533-2012; Gale, Daniel/D-5594-2013; Bakker, Stephan/J-4023-2015;
Prokopenko, Inga/H-3241-2014; Hernandez-Fuentes, Maria/B-5011-2010;
Maxwell, Patrick/C-5557-2008; Lightstone, Liz/M-4331-2014;
OI Abecasis, Goncalo/0000-0003-1509-1825; Forouhi,
Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Wallace, Chris/0000-0001-9755-1703; Lawlor, Debbie
A/0000-0002-6793-2262; Hypponen, Elina/0000-0003-3670-9399; Schalling,
Martin/0000-0001-5011-2922; Bochud, Murielle/0000-0002-5727-0218;
Beckmann, Jacques S /0000-0002-9741-1900; Gale,
Daniel/0000-0002-9170-1579; Bakker, Stephan/0000-0003-3356-6791;
Prokopenko, Inga/0000-0003-1624-7457; Hernandez-Fuentes,
Maria/0000-0002-7558-9441; Maxwell, Patrick/0000-0002-0338-2679;
Sternberg, Michael/0000-0002-1884-5445; Soranzo,
Nicole/0000-0003-1095-3852; Wass, Mark/0000-0001-5428-6479; Stenvinkel,
Peter/0000-0002-8785-4820; sanna, serena/0000-0002-3768-1749;
Lightstone, Liz/0000-0002-4603-4076; Monsalve, Beatriz
Elena/0000-0002-5994-866X; Johnson, Toby/0000-0002-5998-3270
FU Biotechnology and Biological Sciences Research Council [BB/F020481/1];
Department of Health [PHCS/C4/4/016]; Intramural NIH HHS [Z01
AG000675-02]; Medical Research Council [G0400874, G0600420, G0600705,
G0601966, G0700931, G0701863, G0801056, G9521010, MC_U106179471,
MC_U106188470, MC_UP_A100_1003]; Wellcome Trust [091746]
NR 15
TC 134
Z9 138
U1 1
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2010
VL 42
IS 5
BP 373
EP 375
DI 10.1038/ng.566
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 589UK
UT WOS:000277179500005
PM 20383145
ER
PT J
AU Kottgen, A
Pattaro, C
Boger, CA
Fuchsberger, C
Olden, M
Glazer, NL
Parsa, A
Gao, XY
Yang, Q
Smith, AV
O'Connell, JR
Li, M
Schmidt, H
Tanaka, T
Isaacs, A
Ketkar, S
Hwang, SJ
Johnson, AD
Dehghan, A
Teumer, A
Pare, G
Atkinson, EJ
Zeller, T
Lohman, K
Cornelis, MC
Probst-Hensch, NM
Kronenberg, F
Tonjes, A
Hayward, C
Aspelund, T
Eiriksdottir, G
Launer, LJ
Harris, TB
Rampersaud, E
Mitchell, BD
Arking, DE
Boerwinkle, E
Struchalin, M
Cavalieri, M
Singleton, A
Giallauria, F
Metter, J
de Boer, IH
Haritunians, T
Lumley, T
Siscovick, D
Psaty, BM
Zillikens, MC
Oostra, BA
Feitosa, M
Province, M
de Andrade, M
Turner, ST
Schillert, A
Ziegler, A
Wild, PS
Schnabel, RB
Wilde, S
Munzel, T
Leak, TS
Illig, T
Klopp, N
Meisinger, C
Wichmann, HE
Koenig, W
Zgaga, L
Zemunik, T
Kolcic, I
Minelli, C
Hu, FB
Johansson, A
Igl, W
Zaboli, G
Wild, SH
Wright, AF
Campbell, H
Ellinghaus, D
Schreiber, S
Aulchenko, YS
Felix, JF
Rivadeneira, F
Uitterlinden, AG
Hofman, A
Imboden, M
Nitsch, D
Brandstatter, A
Kollerits, B
Kedenko, L
Magi, R
Stumvoll, M
Kovacs, P
Boban, M
Campbell, S
Endlich, K
Volzke, H
Kroemer, HK
Nauck, M
Volker, U
Polasek, O
Vitart, V
Badola, S
Parker, AN
Ridker, PM
Kardia, SLR
Blankenberg, S
Liu, YM
Curhan, GC
Franke, A
Rochat, T
Paulweber, B
Prokopenko, I
Wang, W
Gudnason, V
Shuldiner, AR
Coresh, J
Schmidt, R
Ferrucci, L
Shlipak, MG
van Duijn, CM
Borecki, I
Kramer, BK
Rudan, I
Gyllensten, U
Wilson, JF
Witteman, JC
Pramstaller, PP
Rettig, R
Hastie, N
Chasman, DI
Kao, WH
Heid, IM
Fox, CS
AF Koettgen, Anna
Pattaro, Cristian
Boeger, Carsten A.
Fuchsberger, Christian
Olden, Matthias
Glazer, Nicole L.
Parsa, Afshin
Gao, Xiaoyi
Yang, Qiong
Smith, Albert V.
O'Connell, Jeffrey R.
Li, Man
Schmidt, Helena
Tanaka, Toshiko
Isaacs, Aaron
Ketkar, Shamika
Hwang, Shih-Jen
Johnson, Andrew D.
Dehghan, Abbas
Teumer, Alexander
Pare, Guillaume
Atkinson, Elizabeth J.
Zeller, Tanja
Lohman, Kurt
Cornelis, Marilyn C.
Probst-Hensch, Nicole M.
Kronenberg, Florian
Toenjes, Anke
Hayward, Caroline
Aspelund, Thor
Eiriksdottir, Gudny
Launer, Lenore J.
Harris, Tamara B.
Rampersaud, Evadnie
Mitchell, Braxton D.
Arking, Dan E.
Boerwinkle, Eric
Struchalin, Maksim
Cavalieri, Margherita
Singleton, Andrew
Giallauria, Francesco
Metter, Jeffrey
de Boer, Ian H.
Haritunians, Talin
Lumley, Thomas
Siscovick, David
Psaty, Bruce M.
Zillikens, M. Carola
Oostra, Ben A.
Feitosa, Mary
Province, Michael
de Andrade, Mariza
Turner, Stephen T.
Schillert, Arne
Ziegler, Andreas
Wild, Philipp S.
Schnabel, Renate B.
Wilde, Sandra
Munzel, Thomas
Leak, Tennille S.
Illig, Thomas
Klopp, Norman
Meisinger, Christa
Wichmann, H-Erich
Koenig, Wolfgang
Zgaga, Lina
Zemunik, Tatijana
Kolcic, Ivana
Minelli, Cosetta
Hu, Frank B.
Johansson, Asa
Igl, Wilmar
Zaboli, Ghazal
Wild, Sarah H.
Wright, Alan F.
Campbell, Harry
Ellinghaus, David
Schreiber, Stefan
Aulchenko, Yurii S.
Felix, Janine F.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Hofman, Albert
Imboden, Medea
Nitsch, Dorothea
Brandstaetter, Anita
Kollerits, Barbara
Kedenko, Lyudmyla
Maegi, Reedik
Stumvoll, Michael
Kovacs, Peter
Boban, Mladen
Campbell, Susan
Endlich, Karlhans
Voelzke, Henry
Kroemer, Heyo K.
Nauck, Matthias
Voelker, Uwe
Polasek, Ozren
Vitart, Veronique
Badola, Sunita
Parker, Alexander N.
Ridker, Paul M.
Kardia, Sharon L. R.
Blankenberg, Stefan
Liu, Yongmei
Curhan, Gary C.
Franke, Andre
Rochat, Thierry
Paulweber, Bernhard
Prokopenko, Inga
Wang, Wei
Gudnason, Vilmundur
Shuldiner, Alan R.
Coresh, Josef
Schmidt, Reinhold
Ferrucci, Luigi
Shlipak, Michael G.
van Duijn, Cornelia M.
Borecki, Ingrid
Kraemer, Bernhard K.
Rudan, Igor
Gyllensten, Ulf
Wilson, James F.
Witteman, Jacqueline C.
Pramstaller, Peter P.
Rettig, Rainer
Hastie, Nick
Chasman, Daniel I.
Kao, W. H.
Heid, Iris M.
Fox, Caroline S.
TI New loci associated with kidney function and chronic kidney disease
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GLOMERULAR-FILTRATION-RATE; SERUM CREATININE;
ALSTROM-SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; PROXIMAL TUBULE;
BLOOD-PRESSURE; PROTEIN; GENE; EXPRESSION
AB Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creat-inine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/ 1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
C1 [Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Koettgen, Anna; Li, Man; Coresh, Josef; Kao, W. H.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[Pattaro, Cristian; Fuchsberger, Christian; Minelli, Cosetta; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
[Pattaro, Cristian; Fuchsberger, Christian; Minelli, Cosetta; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Boeger, Carsten A.; Olden, Matthias] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany.
[Olden, Matthias; Heid, Iris M.] Univ Med Ctr Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Parsa, Afshin; O'Connell, Jeffrey R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Gao, Xiaoyi; Ketkar, Shamika; Feitosa, Mary; Province, Michael; Borecki, Ingrid] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Austrian Stroke Prevent Study, Dept Neurogeriatr, Graz, Austria.
[Schmidt, Helena] Med Univ Graz, Univ Clin Neurol, Graz, Austria.
[Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Isaacs, Aaron; Dehghan, Abbas; Oostra, Ben A.; Aulchenko, Yurii S.; Felix, Janine F.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Dehghan, Abbas; Zillikens, M. Carola; Aulchenko, Yurii S.; Felix, Janine F.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C.] NCHA, NGI, Leiden, Netherlands.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
[Atkinson, Elizabeth J.; de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Zeller, Tanja; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Munzel, Thomas; Blankenberg, Stefan] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany.
[Lohman, Kurt] Wake Forest Univ, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Cornelis, Marilyn C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Probst-Hensch, Nicole M.; Imboden, Medea] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Probst-Hensch, Nicole M.; Imboden, Medea] Univ Basel, Basel, Switzerland.
[Kronenberg, Florian; Brandstaetter, Anita; Kollerits, Barbara] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
[Toenjes, Anke; Stumvoll, Michael; Kovacs, Peter] Univ Leipzig, Dept Med, Leipzig, Germany.
[Hayward, Caroline; Wright, Alan F.; Campbell, Susan; Voelker, Uwe; Vitart, Veronique; Hastie, Nick] Western Gen Hosp, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Rampersaud, Evadnie] Miami Inst Human Genom, Miami, FL USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Struchalin, Maksim] Dept Forens Mol Biol, Dept Epidemiol & Biostat, Rotterdam, Netherlands.
[Cavalieri, Margherita; Schmidt, Reinhold] Med Univ Graz, Univ Clin Neurol, Austrian Stroke Prevent Study, Dept Neurogeriatr, Graz, Austria.
[Singleton, Andrew] NIA, Lab Neurogenet, Bethesda, MD 20892 USA.
[Giallauria, Francesco; Metter, Jeffrey; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
[de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Siscovick, David; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Zillikens, M. Carola; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Dept Internal Med, Rotterdam, Netherlands.
[Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN USA.
[Schillert, Arne; Ziegler, Andreas] Med Univ Lubeck, Lubeck Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, D-23538 Lubeck, Germany.
[Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H-Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Koenig, Wolfgang] Univ Ulm Klinikum, Klin Innere Med Kardiol 2, Zentrum Innere Med, Ulm, Germany.
[Zgaga, Lina; Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Zemunik, Tatijana; Boban, Mladen; Wang, Wei] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Kolcic, Ivana; Polasek, Ozren] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
[Johansson, Asa; Igl, Wilmar; Zaboli, Ghazal; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Ellinghaus, David; Schreiber, Stefan; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Nitsch, Dorothea] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Kedenko, Lyudmyla; Paulweber, Bernhard] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Endlich, Karlhans] Ernst Moritz Arndt Univ Greifswald, Inst Anat & Cell Biol, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmacol, Greifswald, Germany.
[Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Badola, Sunita] Amgen Inc, Cambridge, MA USA.
[Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Curhan, Gary C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Rochat, Thierry] Univ Hosp Geneva, Geneva, Switzerland.
[Wang, Wei] Capital Med Univ, Sch Publ Hlth & Family Med, Beijing, Peoples R China.
[Coresh, Josef; Kao, W. H.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kraemer, Bernhard K.] Univ Heidelberg, Mannheim Univ Hosp, Dept Med 5, D-6800 Mannheim, Germany.
[Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM dchasman@rics.bwh.harvard.edu; wkao@jhsph.edu;
iris.heid@klinik.uni-regensburg.de; foxca@nhlbi.nih.gov
RI Hayward, Caroline/M-8818-2016; Franke, Andre/B-2151-2010; Boban,
Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017; Feitosa,
Mary/K-8044-2012; Endlich, Karlhans/G-5485-2013; Johnson,
Andrew/G-6520-2013; Aulchenko, Yurii/M-8270-2013; Meisinger,
Christine/B-5358-2014; Schnabel, Renate/F-6527-2014; Yang,
Qiong/G-5438-2014; Pramstaller, Peter/C-2357-2008; Gudnason,
Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Smith,
Albert/K-5150-2015; Giallauria, Francesco/B-5681-2013; Kronenberg,
Florian/B-1736-2008; Schreiber, Stefan/B-6748-2008; Polasek,
Ozren/B-6002-2011; Fuchsberger, Christian/C-9646-2010; Singleton,
Andrew/C-3010-2009; Aspelund, Thor/F-4826-2011; Aspelund,
Thor/C-5983-2008; Kottgen, Anna/D-2920-2012; Cavalieri,
Margherita/G-8053-2012; Rudan, Igor/I-1467-2012; Johansson,
Asa/G-5270-2011; Ellinghaus, David/G-4467-2012
OI Zgaga, Lina/0000-0003-4089-9703; Ziegler, Andreas/0000-0002-8386-5397;
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Franke, Andre/0000-0003-1530-5811; Kolcic, Ivana/0000-0001-7918-6052;
Feitosa, Mary/0000-0002-0933-2410; Fuchsberger,
Christian/0000-0002-5918-8947; Felix, Janine/0000-0002-9801-5774;
Meisinger, Christa/0000-0002-9026-6544; wang, wei/0000-0002-1430-1360;
Magi, Reedik/0000-0002-2964-6011; Aulchenko, Yurii/0000-0002-7899-1575;
Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James
F/0000-0001-5751-9178; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457; Smith, Albert/0000-0003-1942-5845;
Giallauria, Francesco/0000-0003-4119-9397; Kronenberg,
Florian/0000-0003-2229-1120; Schreiber, Stefan/0000-0003-2254-7771;
Polasek, Ozren/0000-0002-5765-1862; Aspelund, Thor/0000-0002-7998-5433;
Rudan, Igor/0000-0001-6993-6884; Johansson, Asa/0000-0002-2915-4498;
FU Austrian Science Fund FWF [P 20545]; Chief Scientist Office [CZB/4/710];
Medical Research Council [MC_U127561128]; NCRR NIH HHS [K12 RR023250,
K12 RR023250-01, UL1 RR025005, UL1 RR025005-01]; NHGRI NIH HHS [U01
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NR 63
TC 318
Z9 328
U1 6
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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 MAY
PY 2010
VL 42
IS 5
BP 376
EP U34
DI 10.1038/ng.568
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 589UK
UT WOS:000277179500006
PM 20383146
ER
PT J
AU Liu, JZ
Tozzi, F
Waterworth, DM
Pillai, SG
Muglia, P
Middleton, L
Berrettini, W
Knouff, CW
Yuan, X
Waeber, G
Vollenweider, P
Preisig, M
Wareham, NJ
Zhao, JH
Loos, RJF
Barroso, I
Khaw, KT
Grundy, S
Barter, P
Mahley, R
Kesaniemi, A
McPherson, R
Vincent, JB
Strauss, J
Kennedy, JL
Farmer, A
McGuffin, P
Day, R
Matthews, K
Bakke, P
Gulsvik, A
Lucae, S
Ising, M
Brueckl, T
Horstmann, S
Wichmann, HE
Rawal, R
Dahmen, N
Lamina, C
Polasek, O
Zgaga, L
Huffman, J
Campbell, S
Kooner, J
Chambers, JC
Burnett, MS
Devaney, JM
Pichard, AD
Kent, KM
Satler, L
Lindsay, JM
Waksman, R
Epstein, S
Wilson, JF
Wild, SH
Campbell, H
Vitart, V
Reilly, MP
Li, MY
Qu, L
Wilensky, R
Matthai, W
Hakonarson, HH
Rader, DJ
Franke, A
Wittig, M
Schafer, A
Uda, M
Terracciano, A
Xiao, X
Busonero, F
Scheet, P
Schlessinger, D
St Clair, D
Rujescu, D
Abecasis, GR
Grabe, HJ
Teumer, A
Volzke, H
Petersmann, A
John, U
Rudan, I
Hayward, C
Wright, AF
Kolcic, I
Wright, BJ
Thompson, JR
Balmforth, AJ
Hall, AS
Samani, NJ
Anderson, CA
Ahmad, T
Mathew, CG
Parkes, M
Satsangi, J
Caulfield, M
Munroe, PB
Farrall, M
Dominiczak, A
Worthington, J
Thomson, W
Eyre, S
Barton, A
Mooser, V
Francks, C
Marchini, J
AF Liu, Jason Z.
Tozzi, Federica
Waterworth, Dawn M.
Pillai, Sreekumar G.
Muglia, Pierandrea
Middleton, Lefkos
Berrettini, Wade
Knouff, Christopher W.
Yuan, Xin
Waeber, Gerard
Vollenweider, Peter
Preisig, Martin
Wareham, Nicholas J.
Zhao, Jing Hua
Loos, Ruth J. F.
Barroso, Ines
Khaw, Kay-Tee
Grundy, Scott
Barter, Philip
Mahley, Robert
Kesaniemi, Antero
McPherson, Ruth
Vincent, John B.
Strauss, John
Kennedy, James L.
Farmer, Anne
McGuffin, Peter
Day, Richard
Matthews, Keith
Bakke, Per
Gulsvik, Amund
Lucae, Susanne
Ising, Marcus
Brueckl, Tanja
Horstmann, Sonja
Wichmann, H-Erich
Rawal, Rajesh
Dahmen, Norbert
Lamina, Claudia
Polasek, Ozren
Zgaga, Lina
Huffman, Jennifer
Campbell, Susan
Kooner, Jaspal
Chambers, John C.
Burnett, Mary Susan
Devaney, Joseph M.
Pichard, Augusto D.
Kent, Kenneth M.
Satler, Lowell
Lindsay, Joseph M.
Waksman, Ron
Epstein, Stephen
Wilson, James F.
Wild, Sarah H.
Campbell, Harry
Vitart, Veronique
Reilly, Muredach P.
Li, Mingyao
Qu, Liming
Wilensky, Robert
Matthai, William
Hakonarson, Hakon H.
Rader, Daniel J.
Franke, Andre
Wittig, Michael
Schaefer, Arne
Uda, Manuela
Terracciano, Antonio
Xiao, Xiangjun
Busonero, Fabio
Scheet, Paul
Schlessinger, David
St Clair, David
Rujescu, Dan
Abecasis, Goncalo R.
Grabe, Hans Joergen
Teumer, Alexander
Voelzke, Henry
Petersmann, Astrid
John, Ulrich
Rudan, Igor
Hayward, Caroline
Wright, Alan F.
Kolcic, Ivana
Wright, Benjamin J.
Thompson, John R.
Balmforth, Anthony J.
Hall, Alistair S.
Samani, Nilesh J.
Anderson, Carl A.
Ahmad, Tariq
Mathew, Christopher G.
Parkes, Miles
Satsangi, Jack
Caulfield, Mark
Munroe, Patricia B.
Farrall, Martin
Dominiczak, Anna
Worthington, Jane
Thomson, Wendy
Eyre, Steve
Barton, Anne
Mooser, Vincent
Francks, Clyde
Marchini, Jonathan
CA Wellcome Trust Case Control Consor
TI Meta-analysis and imputation refines the association of 15q25 with
smoking quantity
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; NICOTINE DEPENDENCE; LUNG-CANCER;
SUSCEPTIBILITY LOCUS; RISK-FACTORS; VARIANTS; BEHAVIOR; DISEASE; GENES;
SNPS
AB Smoking is a leading global cause of disease and mortality(1). We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
C1 [Liu, Jason Z.; Marchini, Jonathan] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Tozzi, Federica; Muglia, Pierandrea; Francks, Clyde] GlaxoSmithKline, Div Genet, Verona, Italy.
[Waterworth, Dawn M.; Pillai, Sreekumar G.; Yuan, Xin; Mooser, Vincent] GlaxoSmithKline, Div Genet, Upper Merion, PA USA.
[Middleton, Lefkos] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, London SW7 2AZ, England.
[Berrettini, Wade] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Knouff, Christopher W.] GlaxoSmithKline, Div Genet, Res Triangle Pk, NC USA.
[Waeber, Gerard; Vollenweider, Peter; Preisig, Martin] Univ Lausanne, Univ Hosp Ctr, Lausanne, Switzerland.
[Waeber, Gerard; Vollenweider, Peter] Univ Lausanne, Dept Internal Med, Lausanne, Switzerland.
[Preisig, Martin] Univ Lausanne, Dept Psychiat, Lausanne, Switzerland.
[Wareham, Nicholas J.; Zhao, Jing Hua; Loos, Ruth J. F.] Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Barroso, Ines; Anderson, Carl A.] Wellcome Trust Sanger Inst, Hinxton, England.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Grundy, Scott] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA.
[Barter, Philip] Heart Res Inst, Sydney, NSW, Australia.
[Mahley, Robert] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA.
[Mahley, Robert] Amer Hosp, Istanbul, Turkey.
[Kesaniemi, Antero] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland.
[Kesaniemi, Antero] Univ Oulu, Bioctr Oulu, SF-90220 Oulu, Finland.
[McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON, Canada.
[Vincent, John B.; Strauss, John; Kennedy, James L.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Farmer, Anne; McGuffin, Peter] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, Med Res Council Social, London, England.
[Day, Richard; Matthews, Keith] Univ Dundee, Div Med Sci, Ctr Neurosci, Dundee, Scotland.
[Bakke, Per; Gulsvik, Amund] Univ Bergen, Inst Med, Bergen, Norway.
[Lucae, Susanne; Ising, Marcus; Brueckl, Tanja; Horstmann, Sonja] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Wichmann, H-Erich; Rawal, Rajesh; Lamina, Claudia] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-80804 Munich, Germany.
[Dahmen, Norbert] Johannes Gutenberg Univ Mainz, Psychiat Klin & Poliklin, Mainz, Germany.
[Lamina, Claudia] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
[Polasek, Ozren; Kolcic, Ivana] Univ Zagreb, Sch Med, Sch Publ Hlth, Zagreb 41000, Croatia.
[Zgaga, Lina; Wilson, James F.; Wild, Sarah H.; Campbell, Harry; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Huffman, Jennifer; Campbell, Susan; Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol, London, England.
[Burnett, Mary Susan; Devaney, Joseph M.; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Epstein, Stephen] Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA.
[Reilly, Muredach P.; Wilensky, Robert; Matthai, William; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Franke, Andre; Wittig, Michael; Schaefer, Arne] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Uda, Manuela; Busonero, Fabio] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Terracciano, Antonio; Schlessinger, David] NIA, Baltimore, MD USA.
[Xiao, Xiangjun; Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[St Clair, David] Univ Aberdeen, Dept Mental Hlth, Aberdeen, Scotland.
[Rujescu, Dan] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80804 Munich, Germany.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Grabe, Hans Joergen] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[John, Ulrich] Ernst Moritz Arndt Univ Greifswald, Dept Epidemiol & Social Med, Greifswald, Germany.
[Rudan, Igor] Univ Split, Croatian Ctr Global Hlth, Split, Croatia.
[Wright, Benjamin J.; Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, LIGHT, MCRC, Leeds, W Yorkshire, England.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter, Devon, England.
[Mathew, Christopher G.] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England.
[Parkes, Miles] Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge, England.
[Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
[Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, London, England.
[Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England.
[Dominiczak, Anna] Univ Glasgow, Western Infirm, Div Cardiovasc & Med Sci, British Heart Fdn,Glasgow Cardiovasc Res Ctr, Glasgow G11 6NT, Lanark, Scotland.
[Worthington, Jane; Thomson, Wendy; Eyre, Steve; Barton, Anne] Univ Manchester, Fac Med & Human Sci, Arc Epidemiol Res Unit, Sch Translat Med, Manchester M13 9PL, Lancs, England.
[Francks, Clyde] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
RP Marchini, J (reprint author), Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
EM clyde.francks@well.ox.ac.uk; marchini@stats.ox.ac.uk
RI Colaus, PsyColaus/K-6607-2013; McGuffin, Peter/A-1565-2012; Worthington,
Jane/M-9770-2014; Barton, Anne/N-2053-2014; Wilson, James F/A-5704-2009;
terracciano, antonio/B-1884-2008; Abecasis, Goncalo/B-7840-2010;
Polasek, Ozren/B-6002-2011; Lamina, Claudia/F-7608-2010; Rudan,
Igor/I-1467-2012; Francks, Clyde/E-1384-2012; xiao,
xiangjun/B-1722-2013; Anderson, Carl/B-8327-2013; Mathew,
Christopher/G-3434-2015; Hayward, Caroline/M-8818-2016; Franke,
Andre/B-2151-2010; Kolcic, Ivana/E-2713-2017;
OI McGuffin, Peter/0000-0002-9888-2907; Worthington,
Jane/0000-0003-0544-042X; Barton, Anne/0000-0003-3316-2527; Wilson,
James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rudan,
Igor/0000-0001-6993-6884; Anderson, Carl/0000-0003-1719-7009; Mathew,
Christopher/0000-0003-4178-1838; Hayward, Caroline/0000-0002-9405-9550;
Franke, Andre/0000-0003-1530-5811; Kolcic, Ivana/0000-0001-7918-6052;
Tozzi, Federica/0000-0002-3536-2920; Matthews,
Keith/0000-0002-4478-5888; Abecasis, Goncalo/0000-0003-1509-1825; Zgaga,
Lina/0000-0003-4089-9703; Thomson, Wendy/0000-0002-9022-5179; John,
Ulrich/0000-0003-0587-5298; Eyre, Stephen/0000-0002-1251-6974
FU Oxford University; GSK
FX GlaxoSmithKline (GSK), a pharmaceuticals company that is interested in
developing new cessation therapies for smoking, funded a postdoctoral
fellowship for J.Z.L. at Oxford University. GSK also funded the
collection, characterization, and, in some cases, the genotyping and
genotype data preparation for several of the cohorts used in this study.
A. Roses and P. Matthews played crucial roles in establishing and
funding the Medical Genetics activities at GSK. Acknowledgments that are
specific to individual cohorts are given in the Supplementary Note.
NR 38
TC 309
Z9 310
U1 1
U2 37
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 MAY
PY 2010
VL 42
IS 5
BP 436
EP U75
DI 10.1038/ng.572
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 589UK
UT WOS:000277179500016
PM 20418889
ER
PT J
AU Furberg, H
Kim, Y
Dackor, J
Boerwinkle, E
Franceschini, N
Ardissino, D
Bernardinelli, L
Mannucci, PM
Mauri, F
Merlini, PA
Absher, D
Assimes, TL
Fortmann, SP
Iribarren, C
Knowles, JW
Quertermous, T
Ferrucci, L
Tanaka, T
Bis, JC
Furberg, CD
Haritunians, T
McKnight, B
Psaty, BM
Taylor, KD
Thacker, EL
Almgren, P
Groop, L
Ladenvall, C
Boehnke, M
Jackson, AU
Mohlke, KL
Stringham, HM
Tuomilehto, J
Benjamin, EJ
Hwang, SJ
Levy, D
Preis, SR
Vasan, RS
Duan, J
Gejman, PV
Levinson, DF
Sanders, AR
Shi, JX
Lips, EH
Mckay, JD
Agudo, A
Barzan, L
Bencko, V
Benhamou, S
Castellsague, X
Canova, C
Conway, DI
Fabianova, E
Foretova, L
Janout, V
Healy, CM
Holcatova, I
Kjaerheim, K
Lagiou, P
Lissowska, J
Lowry, R
Macfarlane, TV
Mates, D
Richiardi, L
Rudnai, P
Szeszenia-Dabrowska, N
Zaridze, D
Znaor, A
Lathrop, M
Brennan, P
Bandinelli, S
Frayling, TM
Guralnik, JM
Milaneschi, Y
Perry, JRB
Altshuler, D
Elosua, R
Kathiresan, S
Lucas, G
Melander, O
O'Donnell, CJ
Salomaa, V
Schwartz, SM
Voight, BF
Penninx, BW
Smit, JH
Vogelzangs, N
Boomsma, DI
de Geus, EJC
Vink, JM
Willemsen, G
Chanock, SJ
Gu, FY
Hankinson, SE
Hunter, DJ
Hofman, A
Tiemeier, H
Uitterlinden, AG
van Duijn, CM
Walter, S
Chasman, DI
Everett, BM
Pare, G
Ridker, PM
Li, MD
Maes, HH
Audrain-McGovern, J
Posthuma, D
Thornton, LM
Lerman, C
Kaprio, J
Rose, JE
Ioannidis, JPA
Kraft, P
Lin, DY
Sullivan, PF
AF Furberg, Helena
Kim, YunJung
Dackor, Jennifer
Boerwinkle, Eric
Franceschini, Nora
Ardissino, Diego
Bernardinelli, Luisa
Mannucci, Pier M.
Mauri, Francesco
Merlini, Piera A.
Absher, Devin
Assimes, Themistocles L.
Fortmann, Stephen P.
Iribarren, Carlos
Knowles, Joshua W.
Quertermous, Thomas
Ferrucci, Luigi
Tanaka, Toshiko
Bis, Joshua C.
Furberg, Curt D.
Haritunians, Talin
McKnight, Barbara
Psaty, Bruce M.
Taylor, Kent D.
Thacker, Evan L.
Almgren, Peter
Groop, Leif
Ladenvall, Claes
Boehnke, Michael
Jackson, Anne U.
Mohlke, Karen L.
Stringham, Heather M.
Tuomilehto, Jaakko
Benjamin, Emelia J.
Hwang, Shih-Jen
Levy, Daniel
Preis, Sarah Rosner
Vasan, Ramachandran S.
Duan, Jubao
Gejman, Pablo V.
Levinson, Douglas F.
Sanders, Alan R.
Shi, Jianxin
Lips, Esther H.
Mckay, James D.
Agudo, Antonio
Barzan, Luigi
Bencko, Vladimir
Benhamou, Simone
Castellsague, Xavier
Canova, Cristina
Conway, David I.
Fabianova, Eleonora
Foretova, Lenka
Janout, Vladimir
Healy, Claire M.
Holcatova, Ivana
Kjaerheim, Kristina
Lagiou, Pagona
Lissowska, Jolanta
Lowry, Ray
Macfarlane, Tatiana V.
Mates, Dana
Richiardi, Lorenzo
Rudnai, Peter
Szeszenia-Dabrowska, Neonilia
Zaridze, David
Znaor, Ariana
Lathrop, Mark
Brennan, Paul
Bandinelli, Stefania
Frayling, Timothy M.
Guralnik, Jack M.
Milaneschi, Yuri
Perry, John R. B.
Altshuler, David
Elosua, Roberto
Kathiresan, Sek
Lucas, Gavin
Melander, Olle
O'Donnell, Christopher J.
Salomaa, Veikko
Schwartz, Stephen M.
Voight, Benjamin F.
Penninx, Brenda W.
Smit, Johannes H.
Vogelzangs, Nicole
Boomsma, Dorret I.
de Geus, Eco J. C.
Vink, Jacqueline M.
Willemsen, Gonneke
Chanock, Stephen J.
Gu, Fangyi
Hankinson, Susan E.
Hunter, David J.
Hofman, Albert
Tiemeier, Henning
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Walter, Stefan
Chasman, Daniel I.
Everett, Brendan M.
Pare, Guillaume
Ridker, Paul M.
Li, Ming D.
Maes, Hermine H.
Audrain-McGovern, Janet
Posthuma, Danielle
Thornton, Laura M.
Lerman, Caryn
Kaprio, Jaakko
Rose, Jed E.
Ioannidis, John P. A.
Kraft, Peter
Lin, Dan-Yu
Sullivan, Patrick F.
TI Genome-wide meta-analyses identify multiple loci associated with smoking
behavior
SO NATURE GENETICS
LA English
DT Article
ID NICOTINE DEPENDENCE; ENVIRONMENTAL-FACTORS; IMPUTATION; GENES; VARIANTS;
DISEASES; SETS
AB Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
C1 [Furberg, Helena; Kim, YunJung; Dackor, Jennifer; Mohlke, Karen L.; Ioannidis, John P. A.; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
[Furberg, Helena; Mohlke, Karen L.; Ioannidis, John P. A.; Sullivan, Patrick F.] Univ N Carolina, Univ N Carolina Lineberger Comprehens Canc Ct, Chapel Hill, NC USA.
[Boerwinkle, Eric; Lin, Dan-Yu] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric; Lin, Dan-Yu] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Ardissino, Diego] Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy.
[Bernardinelli, Luisa] Univ Cambridge, Stat Lab, Ctr Math Sci, Cambridge CB2 1SB, England.
[Bernardinelli, Luisa] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy.
[Mannucci, Pier M.] Univ Milan, Dept Internal Med & Med Specialties, Fondaz Ist Ricovero & Cura Carattere Sci, Osped Maggiore, Milan, Italy.
[Mauri, Francesco; Merlini, Piera A.] Azienda Osped Niguarda Ca Granda, Dept Cardiol, Milan, Italy.
[Absher, Devin; Ioannidis, John P. A.; Lin, Dan-Yu] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Stanford, CA 94305 USA.
[Fortmann, Stephen P.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Iribarren, Carlos] Kaiser Permanente No Calif Div Res, Oakland, CA USA.
[Tanaka, Toshiko] NIA, Medstart Res Inst, Baltimore, MD 21224 USA.
[Bis, Joshua C.; McKnight, Barbara; Psaty, Bruce M.; Thacker, Evan L.; Schwartz, Stephen M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Furberg, Curt D.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Haritunians, Talin; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA.
[Thacker, Evan L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Almgren, Peter; Groop, Leif; Ladenvall, Claes] Lund Univ, Diabet & Endocrinol Unit, Dept Clin Sci, Malmo, Sweden.
[Boehnke, Michael; Jackson, Anne U.; Stringham, Heather M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Tuomilehto, Jaakko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Tuomilehto, Jaakko] Finland S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[Hwang, Shih-Jen; Preis, Sarah Rosner] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sect Prevent Med, Dept Med, Sch Med, Boston, MA 02118 USA.
[Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Dept Med, Sch Med, Boston, MA 02118 USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ, Ctr Psychiat Genet, HealthSyst Res Inst, Evanston, IL USA.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lips, Esther H.; Mckay, James D.; Brennan, Paul] IARC, Lyon, France.
[Agudo, Antonio; Castellsague, Xavier] Inst Catala Oncol, Barcelona, Spain.
[Barzan, Luigi] Gen Hosp, Pordenone, Italy.
[Bencko, Vladimir; Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Benhamou, Simone] INSERM, U794, Paris, France.
[Benhamou, Simone] Inst Gustave Roussy, Villejuif, France.
[Canova, Cristina] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy.
[Conway, David I.] Univ Glasgow, Sch Dent, Fac Med, Glasgow, Lanark, Scotland.
[Fabianova, Eleonora] Specialized Inst Hyg & Epidemiol, Banska Bystrica, Slovakia.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, CR-77147 Olomouc, Czech Republic.
[Healy, Claire M.] Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland.
[Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway.
[Lagiou, Pagona] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Lissowska, Jolanta] Maria Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lowry, Ray] Univ Newcastle, Sch Dent, Newcastle Upon Tyne, Tyne & Wear, England.
[Macfarlane, Tatiana V.] Univ Aberdeen, Sch Med, Aberdeen AB9 2ZD, Scotland.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Richiardi, Lorenzo] Univ Turin, Ctr Expt Res & Med Studies, Turin, Italy.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Zaridze, David] Inst Carcinogenesis Canc Res Ctr, Moscow, Russia.
[Znaor, Ariana] Croatian Natl Canc Registry, Zagreb, Croatia.
[Lathrop, Mark] Inst Genom Comissariat Energie Atom, Ctr Natl Genotypage, Evry, France.
[Lathrop, Mark] Fondat Jean Dausset Ctr Etud Polymorphisme Humain, Paris, France.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Frayling, Timothy M.; Perry, John R. B.] Univ Exeter, Peninsula Med Sch, Genet Complex Traits, Exeter, Devon, England.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
[Milaneschi, Yuri] Tuscany Hlth Reg Agcy, Florence, Italy.
[Altshuler, David; Kathiresan, Sek] Broad Inst Harvard, Cambridge, MA USA.
[Altshuler, David; Kathiresan, Sek] MIT, Cambridge, MA 02139 USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Altshuler, David; Kathiresan, Sek] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Elosua, Roberto; Lucas, Gavin] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Salomaa, Veikko; Kaprio, Jaakko] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Voight, Benjamin F.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Penninx, Brenda W.; Smit, Johannes H.; Vogelzangs, Nicole] Vrije Univ VU, EMGO Inst, Med Ctr, Amsterdam, Netherlands.
[Penninx, Brenda W.; Smit, Johannes H.; Vogelzangs, Nicole] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Boomsma, Dorret I.; de Geus, Eco J. C.; Vink, Jacqueline M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gu, Fangyi; Hunter, David J.; Kraft, Peter] Harvard Univ, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Hofman, Albert; Tiemeier, Henning; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Walter, Stefan] Erasmus MC, Member Netherlands Consortium Healthy Aging, Dept Epidemiol, Rotterdam, Netherlands.
[Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[van Duijn, Cornelia M.] Erasmus MC, Ctr Med Syst Biol, Rotterdam, Netherlands.
[Walter, Stefan] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Chasman, Daniel I.; Everett, Brendan M.; Pare, Guillaume; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Prevent Med,Sch Med, Boston, MA 02115 USA.
[Everett, Brendan M.; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med,Sch Med, Boston, MA 02115 USA.
[Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA.
[Maes, Hermine H.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Maes, Hermine H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
[Audrain-McGovern, Janet; Lerman, Caryn] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Posthuma, Danielle] Vrije Univ Amsterdam, Dept Funct Gen, Amsterdam, Netherlands.
[Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Med Genom, Amsterdam, Netherlands.
[Thornton, Laura M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Lerman, Caryn] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Kaprio, Jaakko] Univ Helsinki, Inst Mol Med, Helsinki, Finland.
[Rose, Jed E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Genet Epidemiol & Modeling, Boston, MA USA.
Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
RP Furberg, H (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
EM helena_furberg@med.unc.edu; pfsulliv@med.unc.edu
RI ****, ****/F-3368-2011; Voight, Benjamin/F-1775-2011; Ioannidis,
John/G-9836-2011; Vink, Jacqueline/A-7648-2012; Lucas,
Gavin/D-4346-2012; Altshuler, David/A-4476-2009; Kaprio,
Jaakko/A-1820-2008; Hernandez, Tonia/J-9335-2012; Zaridze,
David/K-5605-2013; Mannucci, Pier/C-3102-2014; Gu, Fangyi/I-5957-2014;
Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
de Geus, Eco/M-9318-2015; Benhamou, Simone/K-6554-2015; Castellsague,
Xavier/N-5795-2014;
OI Macfarlane, Tatiana/0000-0002-9392-0812; richiardi,
lorenzo/0000-0003-0316-9402; Tiemeier, Henning/0000-0002-4395-1397;
Benjamin, Emelia/0000-0003-4076-2336; Kjaerheim,
Kristina/0000-0003-0691-3735; Healy, Claire M/0000-0001-7940-4611;
Kaprio, Jaakko/0000-0002-3716-2455; Altshuler,
David/0000-0002-7250-4107; de Geus, Eco/0000-0001-6022-2666;
Castellsague, Xavier/0000-0002-0802-3595; ELOSUA,
ROBERTO/0000-0001-8235-0095; Agudo, Antonio/0000-0001-9900-5677;
Thacker, Evan/0000-0002-3813-0885; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799; Ramachandran,
Vasan/0000-0001-7357-5970
FU University of North Carolina Lineberger Comprehensive Cancer Center
University; US National Cancer Institute [K07 CA118412]; Netherlands
Scientific Organization [NWO 480-05-003]
FX This work was funded by the University of North Carolina Lineberger
Comprehensive Cancer Center University Cancer Research Fund Award and by
US National Cancer Institute K07 CA118412 to H. F. Statistical analyses
were carried out on the Genetic Cluster Computer (see URLs), which is
supported by the Netherlands Scientific Organization (NWO 480-05-003).
Acknowledgments for studies included in TAG are listed in the
Supplementary Note.
NR 41
TC 346
Z9 346
U1 9
U2 60
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 MAY
PY 2010
VL 42
IS 5
BP 441
EP U134
DI 10.1038/ng.571
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 589UK
UT WOS:000277179500017
ER
PT J
AU Gattinoni, L
Ji, Y
Restifo, NP
AF Gattinoni, Luca
Ji, Yun
Restifo, Nicholas P.
TI beta-catenin does not regulate memory T cell phenotype Reply
SO NATURE MEDICINE
LA English
DT Letter
ID DIFFERENTIATION; HEMATOPOIESIS
C1 [Gattinoni, Luca; Ji, Yun; Restifo, Nicholas P.] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Gattinoni, L (reprint author), NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM nicholas_restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Ji,
Yun/B-7245-2009
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009
NR 15
TC 5
Z9 5
U1 0
U2 2
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 MAY
PY 2010
VL 16
IS 5
BP 514
EP 515
DI 10.1038/nm0510-514
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 592QP
UT WOS:000277394700020
ER
PT J
AU Wynn, TA
AF Wynn, Thomas A.
TI Fibrosis under arrest
SO NATURE MEDICINE
LA English
DT Editorial Material
ID EPITHELIAL-CELLS; MECHANISMS
C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011
FU Intramural NIH HHS [ZIA AI001019-04]
NR 11
TC 31
Z9 32
U1 0
U2 1
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 MAY
PY 2010
VL 16
IS 5
BP 523
EP 525
DI 10.1038/nm0510-523
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 592QP
UT WOS:000277394700027
PM 20448575
ER
PT J
AU Epstein, DH
Shaham, Y
AF Epstein, David H.
Shaham, Yavin
TI Cheesecake-eating rats and the question of food addiction
SO NATURE NEUROSCIENCE
LA English
DT Editorial Material
ID WITHDRAWAL; REWARD; DECREASES
C1 [Epstein, David H.; Shaham, Yavin] Natl Inst Drug Abuse, Intramural Res Program, US Natl Inst Hlth, Dept Hlth & Human Serv, Baltimore, MD USA.
RP Epstein, DH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, US Natl Inst Hlth, Dept Hlth & Human Serv, Baltimore, MD USA.
EM yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014
FU Intramural NIH HHS [ZIA DA000434-11]
NR 15
TC 21
Z9 21
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAY
PY 2010
VL 13
IS 5
BP 529
EP 531
DI 10.1038/nn0510-529
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 588JM
UT WOS:000277065700006
PM 20421898
ER
PT J
AU Silver, DL
Watkins-Chow, DE
Schreck, KC
Pierfelice, TJ
Larson, DM
Burnetti, AJ
Liaw, HJ
Myung, K
Walsh, CA
Gaiano, N
Pavan, WJ
AF Silver, Debra L.
Watkins-Chow, Dawn E.
Schreck, Karisa C.
Pierfelice, Tarran J.
Larson, Denise M.
Burnetti, Anthony J.
Liaw, Hung-Jiun
Myung, Kyungjae
Walsh, Christopher A.
Gaiano, Nicholas
Pavan, William J.
TI The exon junction complex component Magoh controls brain size by
regulating neural stem cell division
SO NATURE NEUROSCIENCE
LA English
DT Article
ID MESSENGER-RNA LOCALIZATION; CEREBRAL CORTICAL SIZE; SPINDLE ORIENTATION;
LISSENCEPHALY GENE; HUMAN-CHROMOSOMES; LIS1 EXPRESSION; SECKEL-SYNDROME;
PROTEIN; NEUROGENESIS; NASHI
AB Brain structure and size require precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, and mechanistic explanations of how aberrant NSC division causes the reduced brain size seen in microcephaly are lacking. Here we show that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly because of INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes, as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number and genomic stability. In utero rescue experiments showed that a key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis. Our results uncover requirements for the EJC in brain development, NSC maintenance and mitosis, thereby implicating this complex in the pathogenesis of microcephaly.
C1 [Silver, Debra L.; Watkins-Chow, Dawn E.; Larson, Denise M.; Burnetti, Anthony J.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Schreck, Karisa C.; Pierfelice, Tarran J.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA.
[Liaw, Hung-Jiun; Myung, Kyungjae] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Walsh, Christopher A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MA USA.
[Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Pavan, WJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
EM bpavan@mail.nih.gov
RI Liaw, Hungjiun/G-7034-2014;
OI Liaw, Hungjiun/0000-0002-3481-709X; Watkins-Chow,
Dawn/0000-0002-4355-0868
FU National Institute of General Medical Sciences PRAT
FX For advice, we thank Pavan laboratory members, including L. Baxter for
reading the manuscript. For technical assistance, we thank A. Incao
(mouse husbandry); G. Elliot and A. Chen (mouse transgenics); A. Dutra,
E. Pak and S. Witchovitch (metaphase, SKY, microscopy assistance); S.
Anderson and M. Kirby (FACS analysis); B. Bhorate (microarray
statistics); M. Bryant (pathology analysis); Harvard Partners Center for
Genetics and Genomics (candidate gene sequencing); and J. Fekecs and D.
Leja (assistance with figures). This research was funded in part by an
National Institute of General Medical Sciences PRAT fellowship and
K99/R00 Pathway to Independence Award (to D. L. S.), by the Intramural
Research program of NIH/NHGRI (to W. J. P., K. M.) and by the NIH/NHGRI
(to N.G.). C.A.W. is an Investigator of the Howard Hughes Medical
Institute.
NR 43
TC 71
Z9 72
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAY
PY 2010
VL 13
IS 5
BP 551
EP U53
DI 10.1038/nn.2527
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 588JM
UT WOS:000277065700012
PM 20364144
ER
PT J
AU Harris, TJR
McCormick, F
AF Harris, Timothy J. R.
McCormick, Frank
TI The molecular pathology of cancer
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE
MYELOID-LEUKEMIA; CELL LUNG-CANCER; NF-KAPPA-B; CHRONIC
LYMPHOCYTIC-LEUKEMIA; ARTIFICIAL NEURAL-NETWORKS; POSITIVE
BREAST-CANCER; PROSTATE-CANCER; COLORECTAL-CANCER
AB Rapid technical advances in DNA sequencing and genome-wide association studies are driving the discovery of the germline and somatic mutations that are present in different cancers. Mutations in genes involved in cellular signaling are common, and often shared by tumors that arise in distinct anatomical locations. Here we review the most important molecular changes in different cancers from the perspective of what should be analyzed on a routine basis in the clinic. The paradigms are EGFR mutations in adenocarcinoma of the lung that can be treated with gefitinib, KRAS mutations in colon cancer with respect to treatment with EGFR antibodies, and the use of gene-expression analysis for ER-positive, node-negative breast cancer patients with respect to chemotherapy options. Several other examples in both solid and hematological cancers are also provided. We focus on how disease subtypes can influence therapy and discuss the implications of the impending molecular diagnostic revolution from the point of view of the patients, clinicians, and the diagnostic and pharmaceutical companies. This paradigm shift is occurring first in cancer patient management and is likely to promote the application of these technologies to other diseases.
C1 [Harris, Timothy J. R.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[McCormick, Frank] Univ Calif San Francisco, San Francisco, CA 94158 USA.
RP Harris, TJR (reprint author), NCI, SAIC Frederick, 1050 Boyles St,POB B, Frederick, MD 21702 USA.
EM harristjr@mail.nih.gov
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]
FX The authors would like to thank Drs Javed Khan, David Munroe, Bob
Stephens, Lou Staudt, Snorri Thorgeirsson and Mickey Williams for
providing information and for helpful comments on the manuscript. The
authors would like to apologize for not including references to some of
the original work cited herein. This was for space limitation reasons
only. This project has been funded in whole or in part with federal
funds from the National Cancer Institute and National Institutes of
Health (contract number HHSN261200800001E). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.
NR 166
TC 110
Z9 113
U1 1
U2 46
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 MAY
PY 2010
VL 7
IS 5
BP 251
EP 265
DI 10.1038/nrclinonc.2010.41
PG 15
WC Oncology
SC Oncology
GA 589UM
UT WOS:000277179700006
PM 20351699
ER
PT J
AU Lambotin, M
Raghuraman, S
Stoll-Keller, F
Baumert, TF
Barth, H
AF Lambotin, Melanie
Raghuraman, Sukanya
Stoll-Keller, Francoise
Baumert, Thomas F.
Barth, Heidi
TI A look behind closed doors: interaction of persistent viruses with
dendritic cells
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-PRODUCING
CELLS; INHIBITS TLR9-MEDIATED ACTIVATION; PRIMARY HIV-1 INFECTION;
CHRONIC HCV INFECTION; NATURAL-KILLER-CELLS; IFN-ALPHA PRODUCTION;
RECEPTOR CLASS-B; DC-SIGN
AB Persistent infections with HIV, hepatitis B virus and hepatitis C virus are major causes of morbidity and mortality worldwide. As sentinels of the immune system, dendritic cells (DCs) are crucial for the generation of protective antiviral immunity. Recent advances in our understanding of the role of DCs during infection with these viruses provide insights into the mechanisms used by these viruses to exploit DC function and evade innate and adaptive immunity. In this Review we highlight the current knowledge about the interaction between DCs and these viruses and the underlying mechanisms that might influence the outcome of viral infections.
C1 [Lambotin, Melanie; Stoll-Keller, Francoise; Baumert, Thomas F.; Barth, Heidi] INSERM, U748, F-67000 Strasbourg, France.
[Lambotin, Melanie; Stoll-Keller, Francoise; Baumert, Thomas F.; Barth, Heidi] Univ Strasbourg, F-67081 Strasbourg, France.
[Raghuraman, Sukanya] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Baumert, Thomas F.] Hop Univ Strasbourg, Serv Hepatogastroenterol, F-67000 Strasbourg, France.
RP Barth, H (reprint author), INSERM, U748, 3 Rue Koeberie, F-67000 Strasbourg, France.
EM barth@unistra.fr
FU University of Strasbourg, France; Deutsche Forschungsgemeinschaft;
National Institute of Diabetes and Digestive and Kidney Diseases (US
National Institutes of Health); European Union; French Agence Nationale
de la Recherche; French Agence Nationale de Recherche sur le SIDA et les
Hepatites Virales; German Else Kroner-Fresenius Stiftung
FX This work was supported by the CONECTUS-OSEO programme of the University
of Strasbourg, France, the Deutsche Forschungsgemeinschaft, the
intramural research programme of the National Institute of Diabetes and
Digestive and Kidney Diseases (US National Institutes of Health), the
European Union (through the programmes ERC HEPCENT and Interreg IV
HEPATO-REGIO-NET), the French Agence Nationale de la Recherche, the
French Agence Nationale de Recherche sur le SIDA et les Hepatites
Virales, and the German Else Kroner-Fresenius Stiftung.
NR 133
TC 36
Z9 40
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD MAY
PY 2010
VL 8
IS 5
BP 350
EP 360
DI 10.1038/nrmicro2332
PG 11
WC Microbiology
SC Microbiology
GA 584XT
UT WOS:000276788300012
PM 20372157
ER
PT J
AU Chow, WH
Dong, LM
Devesa, SS
AF Chow, Wong-Ho
Dong, Linda M.
Devesa, Susan S.
TI Epidemiology and risk factors for kidney cancer
SO NATURE REVIEWS UROLOGY
LA English
DT Review
ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU GENE; BODY-MASS INDEX;
A-META-ANALYSIS; DRINKING-WATER; DIETARY ACRYLAMIDE; CIGARETTE-SMOKING;
PHYSICAL-ACTIVITY; POOLED ANALYSIS; VITAMIN-D
AB After more than two decades of rising rates, in recent years the total kidney cancer incidence worldwide has shown signs of stabilizing, or even decreasing. In adults, kidney cancer consists of renal cell carcinoma (RCC), the predominant form, and renal transitional cell carcinoma (RTCC); these types primarily arise in the renal parenchyma and renal pelvis, respectively. Although temporal trends by kidney cancer type are not well established worldwide, incidence of RCC in the US has continued to rise, mainly for early-stage tumors, while that of RTCC has declined, and total kidney cancer mortality rates have leveled. Stabilization of kidney cancer mortality rates has also been reported in Europe. These trends are consistent with reports of increasing incidental diagnoses and a downward shift in tumor stage and size in clinical series. The changing prevalence of known risk factors for RCC, including cigarette smoking, obesity, and hypertension, is also likely to affect incidence trends, although their relative impact may differ between populations. Accumulating evidence suggests an etiologic role in RCC for physical activity, alcohol consumption, occupational exposure to trichloroethylene, and high parity among women, but further research is needed into the potential causal effects of these factors. Genetic factors and their interaction with environmental exposures are believed to influence risk of developing RCC, but a limited number of studies using candidate-gene approaches have not produced conclusive results. Large consortium efforts employing genome-wide scanning technology are underway, which hold promise for novel discoveries in renal carcinogenesis.
C1 [Chow, Wong-Ho; Dong, Linda M.; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,EPS 8100, Bethesda, MD 20892 USA.
EM choww@mail.nih.gov
RI Liao, Linda/B-3960-2011
FU National Institutes of Health
FX The authors express their appreciation to the cancer registries
contributing data to the IARC Cancer Incidence in Five Continents and
the NCI Surveillance, Epidemiology, and End Results (SEER) Program, and
to the dedicated program staff of the IARC and NCI. They also thank
David Check of the Division of Cancer Epidemiology and Genetics, NCI for
figure preparation using tabulated data generated from NCI's SEER and
IARC's Cancer Incidence in Five Continents series. This Review was
supported by the Intramural Research Program of the National Institutes
of Health.
NR 137
TC 372
Z9 383
U1 4
U2 52
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4812
EI 1759-4820
J9 NAT REV UROL
JI Nat. Rev. Urol.
PD MAY
PY 2010
VL 7
IS 5
BP 245
EP 257
DI 10.1038/nrurol.2010.46
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 592QF
UT WOS:000277393600004
PM 20448658
ER
PT J
AU Bratslavsky, G
Linehan, WM
AF Bratslavsky, Gennady
Linehan, W. Marston
TI Long-term management of bilateral, multifocal, recurrent renal carcinoma
SO NATURE REVIEWS UROLOGY
LA English
DT Review
ID HIPPEL-LINDAU-DISEASE; NEPHRON-SPARING SURGERY; CHRONIC KIDNEY-DISEASE;
CELL-CARCINOMA; PARTIAL NEPHRECTOMY; RADICAL NEPHRECTOMY;
CARDIOVASCULAR-DISEASE; FOLLOW-UP; CLINICOPATHOLOGICAL FEATURES;
INTRAOPERATIVE ULTRASOUND
AB Patients with bilateral multifocal renal cell carcinoma are at increased risk of developing locally recurrent or de novo tumors after nephron-sparing procedures. When dealing with recurrent renal masses the options are limited to observation, total nephrectomy, ablation, or repeat surgical intervention. The main reason for recurrence after nephron-sparing surgery is likely to be the presence of multifocal disease, which is identified in 4.3-25.0% of radical nephrectomy specimen. Bilateral renal involvement is seen in almost 90% of cases of multifocal renal carcinoma, and conversely the majority of patients with bilateral disease will have multifocal tumors. Many patients who are treated for multifocal disease, therefore, require subsequent surgical interventions. The outcome data for repeat renal interventions demonstrate reasonable functional and oncologic outcomes despite higher rates of perioperative complications. Our own results support the use of reoperative renal surgery rather than total nephrectomy and renal replacement therapy.
C1 [Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. Desiree Lie,
University of California, Irvine, CA, is the author of and is solely
responsible for the content of the learning objectives, questions and
answers of the MedscapeCME-accredited continuing medical education
activity associated with this article.
NR 84
TC 17
Z9 22
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4812
J9 NAT REV UROL
JI Nat. Rev. Urol.
PD MAY
PY 2010
VL 7
IS 5
BP 267
EP 275
DI 10.1038/nrurol.2010.44
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 592QF
UT WOS:000277393600006
PM 20448660
ER
PT J
AU Linehan, WM
Srinivasan, R
Schmidt, LS
AF Linehan, W. Marston
Srinivasan, Ramaprasad
Schmidt, Laura S.
TI The genetic basis of kidney cancer: a metabolic disease
SO NATURE REVIEWS UROLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; VONHIPPEL-LINDAU DISEASE;
TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL
GROWTH-FACTOR; SMALL-MOLECULE INHIBITORS; IRON-REGULATORY PROTEINS;
FUMARATE-HYDRATASE GENE; HEREDITARY LEIOMYOMATOSIS
AB Kidney cancer is not a single disease but comprises a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates hypoxia-inducible factor (HIF) levels in the cell. HGF-MET signaling affects the LKB1-AMPK energy sensing cascade. The FLCN-FNIP1-FNIP2 complex binds AMPK and, therefore, might interact with the cellular energy and nutrient sensing pathways AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR. TSC1-TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit. FH and SDH have a central role in the mitochondrial tricarboxylic acid cycle, which is coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy or nutrient sensing, suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease.
C1 [Linehan, W. Marston; Srinivasan, Ramaprasad; Schmidt, Laura S.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,Bldg 10,CRC Room 1-5940, Bethesda, MD 20892 USA.
EM wml@nih.gov
FU National Institute of Health, National Cancer Institute, Center for
Cancer Research [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Health, National Cancer Institute, Center
for Cancer Research and funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Heath and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. The authors
acknowledge the outstanding editorial and graphics support by Georgia
Shaw.
NR 93
TC 259
Z9 266
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4812
J9 NAT REV UROL
JI Nat. Rev. Urol.
PD MAY
PY 2010
VL 7
IS 5
BP 277
EP 285
DI 10.1038/nrurol.2010.47
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 592QF
UT WOS:000277393600007
PM 20448661
ER
PT J
AU Sellers, JR
Veigel, C
AF Sellers, James R.
Veigel, Claudia
TI Direct observation of the myosin-Va power stroke and its reversal
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID LOAD-DEPENDENT KINETICS; OPTICAL TWEEZERS; ACTOMYOSIN-V; PROCESSIVE
MOVEMENT; STEPPING KINETICS; FORCE GENERATION; MOLECULAR-MODEL; ADP
BINDING; MUSCLE; MOTOR
AB Complex forms of cellular motility, including cell division, organelle trafficking or signal amplification in the auditory system, require strong coordination of the myosin motors involved. The most basic mechanism of coordination is via direct mechanical interactions of individual motor heads leading to modification of their mechanochemical cycles. Here we used an optical trap-based assay to investigate the reversibility of the force-generating conformational change ( power stroke) of single myosin-Va motor heads. By applying load to the head shortly after binding to actin, we found that, at a certain load, the power stroke could be reversed, and the head fluctuated between an actin-bound pre- and a post-power stroke conformation. This load-dependent mechanical instability might be critical to coordinate the heads of processive, dimeric myosin-Va. Nonlinear response to load leading to coordination or oscillations amongst motors might be relevant for many cellular functions.
C1 [Veigel, Claudia] Natl Inst Med Res, London NW7 1AA, England.
[Veigel, Claudia] Univ Munich, Dept Cellular Physiol, Munich, Germany.
[Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Veigel, C (reprint author), Natl Inst Med Res, Mill Hill, London NW7 1AA, England.
EM claudia.veigel@med.uni-muenchen.de
FU UK Medical Research Council; Royal Society UK; US National Institutes of
Health
FX We thank C. Schmidt and J. Molloy for stimulating discussions, E. Harvey
for technical assistance and J. Hammer III (Laboratories of Cell
Biology, National Heart, Lung, and Blood Institute, US National
Institutes of Health) for kindly supplying the myosin-Va clone. We are
also grateful to the UK Medical Research Council, The Royal Society UK
and the US National Institutes of Health for grant support.
NR 47
TC 34
Z9 35
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAY
PY 2010
VL 17
IS 5
BP 590
EP U88
DI 10.1038/nsmb.1820
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 591UP
UT WOS:000277330700012
PM 20418880
ER
PT J
AU Barski, A
Chepelev, I
Liko, D
Cuddapah, S
Fleming, AB
Birch, J
Cui, KR
White, RJ
Zhao, K
AF Barski, Artem
Chepelev, Iouri
Liko, Dritan
Cuddapah, Suresh
Fleming, Alastair B.
Birch, Joanna
Cui, Kairong
White, Robert J.
Zhao, Keji
TI Pol II and its associated epigenetic marks are present at Pol
III-transcribed noncoding RNA genes
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID POLYMERASE-III; HISTONE ACETYLATION; HUMAN GENOME; C-MYC; CHROMATIN;
ACTIVATION; METHYLATIONS; EXPRESSION; REPRESSION; PROMOTERS
AB Epigenetic control is an important aspect of gene regulation. Despite detailed understanding of protein-coding gene expression, the transcription of noncoding RNA genes by RNA polymerase III (Pol III) is less well characterized. Here we profile the epigenetic features of Pol III target genes throughout the human genome. This reveals that the chromatin landscape of Pol III-transcribed genes resembles that of Pol II templates in many ways, although there are also clear differences. Our analysis also uncovered an entirely unexpected phenomenon: namely, that Pol II is present at the majority of genomic loci that are bound by Pol III.
C1 [Barski, Artem; Chepelev, Iouri; Cuddapah, Suresh; Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Liko, Dritan; Fleming, Alastair B.; Birch, Joanna; White, Robert J.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
RP White, RJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rwhite@udcf.gla.ac.uk; zhaok@nhlbi.nih.gov
RI Liko, Dritan/A-3549-2011;
OI Barski, Artem/0000-0002-1861-5316
FU US National Institutes of Health, National Heart, Lung, and Blood
Institute [1K22HL098691-01]; Cancer Research UK
FX We thank D. E. Schones for assistance with the Solexa Pipeline analysis
and helpful discussions. This work was supported by the Intramural
Research Program of the US National Institutes of Health, National
Heart, Lung, and Blood Institute (K.Z.) and Cancer Research UK (R.J.W.).
A. B. was additionally supported by 1K22HL098691-01 Career Transition
Award from the National Heart, Lung, and Blood Institute, US National
Institutes of Health.
NR 48
TC 86
Z9 87
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAY
PY 2010
VL 17
IS 5
BP 629
EP U132
DI 10.1038/nsmb.1806
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 591UP
UT WOS:000277330700019
PM 20418881
ER
PT J
AU Rifkin, DE
Katz, R
Chonchol, M
Fried, LF
Cao, J
de Boer, IH
Siscovick, DS
Shlipak, MG
Sarnak, MJ
AF Rifkin, Dena E.
Katz, Ronit
Chonchol, Michel
Fried, Linda F.
Cao, Jie
de Boer, Ian H.
Siscovick, David S.
Shlipak, Michael G.
Sarnak, Mark J.
TI Albuminuria, impaired kidney function and cardiovascular outcomes or
mortality in the elderly
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE albuminuria; aging; cardiovascular diseases; kidney function; mortality
ID GLOMERULAR-FILTRATION-RATE; ALL-CAUSE MORTALITY; RISK-FACTOR;
CYSTATIN-C; RENAL-INSUFFICIENCY; DIABETES-MELLITUS; DISEASE;
MICROALBUMINURIA; ASSOCIATION; DYSFUNCTION
AB Methods. We examined associations of these markers with mortality and cardiovascular outcomes during a median follow-up of 8.3 years in 3291 older adults in the Cardiovascular Health Study. Kidney disease was assessed using urinary albumin/creatinine ratio (ACR), cystatin C and Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR). We defined subgroups based on presence of microalbuminuria (MA, ACR > 30 mg/g) and categories of normal kidney function (cystatin C < 1.0 mg/L and eGFR > 60 mL/min/1.73 m(2)); preclinical kidney disease (cystatin C level > 1.0 mg/l but eGFR > 60 mL/min/1.73 m(2)); and chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). Cox proportional hazards models were used to examine associations between these six subgroups and all-cause or cardiovascular mortality, myocardial infarction and heart failure.
Results. One thousand one hundred fifty (34.9%) had normal kidney function (12.2% with MA), 1518 (46.1%) had preclinical kidney disease (17.9% with MA) and 622 (18.9%) had CKD (47% with MA). After adjustment, the presence of either preclinical kidney disease or MA was associated with an over 50% increase in mortality risk; the presence of both was associated with a 2.4-fold mortality risk. Those with CKD and MA were at highest risk, with a nearly 4-fold mortality risk.
Conclusion. Elevated cystatin C and albuminuria are common, identify different subsets of the older population, and are independent, graded risk factors for cardiovascular disease and mortality.
C1 [Rifkin, Dena E.; Sarnak, Mark J.] Tufts Med Ctr, Boston, MA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Rifkin, Dena E.; Sarnak, Mark J.] Tufts Univ, Sch Med, Medford, MA 02155 USA.
[Katz, Ronit; de Boer, Ian H.; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA.
[Chonchol, Michel] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
[Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh Vet Affairs Healthcare Syst, Pittsburgh, PA 15260 USA.
[Cao, Jie] NIH, Bethesda, MD 20892 USA.
RP Rifkin, DE (reprint author), Tufts Med Ctr, Boston, MA USA.
EM drifkin@ucsd.edu
FU National Heart, Lung, and Blood Institute [R01-AG-027002, N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, U01 HL080295]; National Institute of Neurological
Disorders and Stroke
FX The research reported in this articlewas supported by contract numbers
R01-AG-027002, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01
HL080295 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. A full list of principal CHS investigators and
institutions can be found at http://www.chs-nhlbi.org/pi.htm.
NR 36
TC 45
Z9 46
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2010
VL 25
IS 5
BP 1560
EP 1567
DI 10.1093/ndt/gfp646
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 587LR
UT WOS:000276994400035
PM 20008829
ER
PT J
AU Guerreiro, RJ
Baquero, M
Blesa, R
Boada, M
Bras, JM
Bullido, MJ
Calado, A
Crook, R
Ferreira, C
Frank, A
Gomez-Isla, T
Hernandez, I
Lleo, A
Machado, A
Martinez-Lage, P
Masdeu, J
Molina-Porcel, L
Molinuevo, JL
Pastor, P
Perez-Tur, J
Relvas, R
Oliveira, CR
Ribeiro, MH
Rogaeva, E
Sa, A
Samaranch, L
Sanchez-Valle, R
Santana, I
Tarraga, L
Valdivieso, F
Singleton, A
Hardy, J
Clarimon, J
AF Guerreiro, Rita Joao
Baquero, Miguel
Blesa, Rafael
Boada, Merce
Bras, Jose Miguel
Bullido, Maria J.
Calado, Ana
Crook, Richard
Ferreira, Carla
Frank, Ana
Gomez-Isla, Teresa
Hernandez, Isabel
Lleo, Alberto
Machado, Alvaro
Martinez-Lage, Pablo
Masdeu, Jose
Molina-Porcel, Laura
Molinuevo, Jose L.
Pastor, Pau
Perez-Tur, Jordi
Relvas, Rute
Oliveira, Catarina Resende
Ribeiro, Maria Helena
Rogaeva, Ekaterina
Sa, Alfredo
Samaranch, Lluis
Sanchez-Valle, Raquel
Santana, Isabel
Tarraga, Lluis
Valdivieso, Fernando
Singleton, Andrew
Hardy, John
Clarimon, Jordi
TI Genetic screening of Alzheimer's disease genes in Iberian and African
samples yields novel mutations in presenilins and APP
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Early-onset Alzheimer's disease; Presenilins; APP; Mutations
ID AMYLOID PRECURSOR PROTEIN; MUTANT PRESENILIN-1; PATHOGENIC MUTATION;
MISSENSE MUTATIONS; GAMMA-SECRETASE; BETA-PROTEIN; PARKINSONISM;
PHENOTYPE; DIAGNOSIS; DEMENTIA
AB Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer's disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early-onset AD (mean age at onset of 52.9 years; range 31-64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new non-synonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Blesa, Rafael; Gomez-Isla, Teresa; Lleo, Alberto; Molina-Porcel, Laura] Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, Barcelona 08025, Spain.
[Guerreiro, Rita Joao; Bras, Jose Miguel; Singleton, Andrew; Hardy, John] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Guerreiro, Rita Joao; Bras, Jose Miguel; Oliveira, Catarina Resende; Ribeiro, Maria Helena] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Baquero, Miguel] Hosp Univ La Fe, Dept Neurol, Valencia, Spain.
[Boada, Merce; Hernandez, Isabel; Martinez-Lage, Pablo; Tarraga, Lluis] Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Alzheimer Res Ctr, Barcelona, Spain.
[Bullido, Maria J.; Valdivieso, Fernando] Ctr Biol Mol Severo Ochoa, Madrid, Spain.
[Calado, Ana; Relvas, Rute] Hosp Santo Antonio Capuchos, Lisbon, Portugal.
[Crook, Richard] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Ferreira, Carla; Machado, Alvaro] Hosp Sao Marcos, Braga, Portugal.
[Frank, Ana] Hosp Univ La Paz, Serv Neurol, Madrid, Spain.
[Pastor, Pau; Samaranch, Lluis] Univ Navarra, Neurogenet Lab, Div Neurociences, CIMA,Med Sch, E-31080 Pamplona, Spain.
[Molinuevo, Jose L.; Sanchez-Valle, Raquel] Hosp Clin Barcelona, Inst Neurosci, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain.
[Molinuevo, Jose L.; Sanchez-Valle, Raquel] Univ Barcelona, Barcelona, Spain.
[Perez-Tur, Jordi] CSIC, Inst Biomed Valencia, Valencia, Spain.
[Oliveira, Catarina Resende; Santana, Isabel] Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal.
[Rogaeva, Ekaterina] Univ Hlth Network, Dept Med, Div Neurol, Toronto, ON, Canada.
[Sa, Alfredo] Hosp Leiria, Leiria, Portugal.
[Blesa, Rafael; Bullido, Maria J.; Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Blesa, Rafael; Bullido, Maria J.; Hardy, John] Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
[Frank, Ana; Gomez-Isla, Teresa; Lleo, Alberto; Molina-Porcel, Laura; Pastor, Pau; Perez-Tur, Jordi; Samaranch, Lluis; Valdivieso, Fernando; Clarimon, Jordi] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain.
RP Clarimon, J (reprint author), Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, St Antoni Ma Claret 167, Barcelona 08025, Spain.
EM jclarimon@santpau.cat
RI Oliveira, Catarina/F-3685-2010; Perez-Tur, Jordi/A-2143-2010; Masdeu,
Joseph/B-5052-2010; Singleton, Andrew/C-3010-2009; Pastor,
Pau/C-9834-2009; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011;
Bras, Jose/A-1428-2011; Frank Garcia, Ana/I-5159-2015; Bullido,
Maria/C-8509-2014;
OI Oliveira, Catarina/0000-0001-6942-4328; Perez-Tur,
Jordi/0000-0002-9111-1712; Pastor, Pau/0000-0002-7493-8777; Frank
Garcia, Ana/0000-0003-3858-9116; Bullido, Maria/0000-0002-6477-1117;
Clarimon, Jordi/0000-0002-6824-6942; Santana,
Isabel/0000-0002-8114-9434; Molinuevo, Jose Luis/0000-0003-0485-6001
FU Intramural Research Program of NIA [1 Z01 AG000950-06 2007]; Canadian
Institutes of Health Research; Fundacao para a Ciencia e Tecnologia,
Portugal [SFRH/BD/27442/2006, SFRH/BD/29647/2006]
FX We thank the patients and their families for the Alzheimer samples and
the CEPH-HGDP for the African samples. This study was supported by the
Intramural Research Program of NIA (1 Z01 AG000950-06 2007); the
Canadian Institutes of Health Research (ER); and grants #
SFRH/BD/27442/2006 and SFRH/BD/29647/2006 from Fundacao para a Ciencia e
Tecnologia, Portugal. We would like to thank "Banc de Teixits
Neurolegics", at the University of Barcelona, Hospital Clinic, Spain,
for their contribution on pathological analyses of the APP mutation
carrier.
NR 33
TC 78
Z9 81
U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2010
VL 31
IS 5
BP 725
EP 731
DI 10.1016/j.neurobiolaging.2008.06.012
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 577KJ
UT WOS:000276221600001
PM 18667258
ER
PT J
AU Rosenbaum, RS
Furey, ML
Horwitz, B
Grady, CL
AF Rosenbaum, R. Shayna
Furey, Maura L.
Horwitz, Barry
Grady, Cheryl L.
TI Altered connectivity among emotion-related brain regions during
short-term memory in Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Aging; Structural equation modeling; Amygdala; Hippocampus; Inferior
prefrontal cortex; Plasticity
ID POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE METABOLIC RATES; FACIAL
EXPRESSIONS; FUNCTIONAL CONNECTIVITY; NEURAL MECHANISMS; NETWORK
ANALYSIS; FRONTAL-CORTEX; AMYGDALA; ACTIVATION; EXPLICIT
AB A PET study of patients with Alzheimer's disease (AD) engaged in a delayed match-to-sample face recognition task revealed that performance declines as a function of increasing delay, a pattern accompanied by reduced functional connectivity of prefrontal cortex but increased connectivity of the left amygdala. Here, we characterize the changes in interactions within this amygdalar circuit across the memory delays using structural equation modeling. The magnitude of effective connections was found to be much greater in the patients than in the controls, notably from the left amygdala to left inferior prefrontal cortex, which, in turn, influenced its right homologue. The influence from the amygdala to the left hippocampus, in contrast, was not strong in either group. We interpret this pattern of interactions as possibly reflecting the compensatory recruitment of a dynamic neural network, perhaps involved in implicit emotional processing, in the context of a faulty executive maintenance and retrieval system. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Rosenbaum, R. Shayna] York Univ, Dept Psychol, N York, ON M3J 1P3, Canada.
[Rosenbaum, R. Shayna; Grady, Cheryl L.] Rotman Res Inst, Toronto, ON M5A 2E1, Canada.
[Furey, Maura L.] NIMH, Neuroimaging Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA.
[Grady, Cheryl L.] Univ Toronto, Dept Psychol, Toronto, ON M5S 3G3, Canada.
[Grady, Cheryl L.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 3G3, Canada.
RP Rosenbaum, RS (reprint author), York Univ, Dept Psychol, 4700 Keele St, N York, ON M3J 1P3, Canada.
EM shaynar@yorku.ca
RI Furey, Maura/H-5273-2013
FU Canadian Institutes of Health Research (CIHR) [MOP 14036]; Natural
Sciences and Engineering Research Council; Canada Research Chairs
program; NIDCD Intramural Research Program
FX This work was supported by a grant from the Canadian Institutes of
Health Research (CIHR MOP 14036). R.S.R. is supported by a CIHR New
Investigator Award and the Natural Sciences and Engineering Research
Council, and C.L.G. is supported by the Canada Research Chairs program.
B.H. acknowledges the support of the NIDCD Intramural Research Program.
NR 47
TC 16
Z9 16
U1 4
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2010
VL 31
IS 5
BP 780
EP 786
DI 10.1016/j.neurobiolaging.2008.06.002
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 577KJ
UT WOS:000276221600008
PM 18639365
ER
PT J
AU Sambataro, F
Murty, VP
Callicott, JH
Tan, HY
Das, S
Weinberger, DR
Mattay, VS
AF Sambataro, Fabio
Murty, Vishnu P.
Callicott, Joseph H.
Tan, Hao-Yang
Das, Saumitra
Weinberger, Daniel R.
Mattay, Venkata S.
TI Age-related alterations in default mode network: Impact on working
memory performance
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Functional magnetic resonance imaging; Aging; Default mode;
Connectivity; Working memory
ID STRIATAL DOPAMINE TRANSPORTER; BOLD SIGNAL FLUCTUATIONS; RESTING HUMAN
BRAIN; ALZHEIMERS-DISEASE; FUNCTIONAL MRI; PREFRONTAL CORTEX; MOTOR
CORTEX; VISUAL-ATTENTION; RHESUS-MONKEY; AGING BRAIN
AB The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand. Published by Elsevier Inc.
C1 [Sambataro, Fabio; Murty, Vishnu P.; Callicott, Joseph H.; Tan, Hao-Yang; Das, Saumitra; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
RP Mattay, VS (reprint author), NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bldg 10,Room 3C-108, Bethesda, MD 20892 USA.
EM vsm@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334
FU National Institute of Mental Health Intramural Research Program
FX We thank Prof. Alessandro Bertolino, MD, PhD, Annabella Di Giorgio, MD,
PhD, and Nerve Lemaitre, PhD for helpful discussions and Jennifer Brook,
BA and Matt Emery, BS for assistance in data analysis. This work was
supported by the National Institute of Mental Health Intramural Research
Program.
NR 88
TC 181
Z9 183
U1 3
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2010
VL 31
IS 5
BP 839
EP 852
DI 10.1016/j.neurobiolaging.2008.05.022
PG 14
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 577KJ
UT WOS:000276221600014
PM 18674847
ER
PT J
AU Skinbjerg, M
Liow, JS
Seneca, N
Hong, JS
Lu, SY
Thorsell, A
Heilig, M
Pike, VW
Halldin, C
Sibley, DR
Innis, RB
AF Skinbjerg, Mette
Liow, Jeih-San
Seneca, Nicholas
Hong, Jinsoo
Lu, Shuiyu
Thorsell, Annika
Heilig, Markus
Pike, Victor W.
Halldin, Christer
Sibley, David R.
Innis, Robert B.
TI D-2 dopamine receptor internalization prolongs the decrease of
radioligand binding after amphetamine: A PET study in a receptor
internalization-deficient mouse model
SO NEUROIMAGE
LA English
DT Article
DE [C-11]MNPA; [F-18]fallypride; Dopamine receptor; Internalization;
Arrestin3; PET
ID POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN PRIMATE BRAIN; HIGH-AFFINITY
STATE; AGONIST RADIOTRACER; ENDOGENOUS DOPAMINE; G-PROTEIN; EX-VIVO;
BETA-ARRESTIN-2; RADIOSYNTHESIS; TRAFFICKING
AB Dopamine released by amphetamine decreases the in vivo binding of PET radioligands to the dopamine D-2 receptor. Although concentrations of extracellular dopamine largely return to baseline within 1 to 2 h after amphetamine treatment, radioligand binding remains decreased for several hours. The purpose of this study was to determine whether the prolonged decrease of radioligand binding after amphetamine administration is caused by receptor internalization. To distinguish dopamine displacement from receptor internalization, we used wild-type and arrestin3 (arr3) knockout mice, which are incapable of internalizing D-2 receptors. In addition, we used both the D-2 selective agonist [C-11]MNPA (which is thought to bind to the high affinity state of the receptor) and the D-2 selective antagonist [F-18]fallypride (which does not differentiate between high and low affinity state). After an initial baseline scan, animals were divided in three groups for a second scan: either 30 min or 4 h after amphetamine administration (3 mg/kg, i.p.) or as retest. At 30 min, [C-11]MNPA showed greater displacement than [F-18]fallypride, but each radioligand gave similar displacement in knockout and wild-type mice. At 4 h, the binding of both radioligands returned to baseline in arr3 knockout mice, but remained decreased in wild-type mice. Radioligand binding was unaltered on retest scanning. Our results suggest that the prolonged decrease of radioligand binding after amphetamine is mainly due to internalization of the D-2 receptor rather than dopamine displacement. In addition, this study demonstrates the utility of small animal PET to study receptor trafficking in vivo in genetically modified mice. Published by Elsevier Inc.
C1 [Skinbjerg, Mette; Liow, Jeih-San; Seneca, Nicholas; Hong, Jinsoo; Lu, Shuiyu; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Skinbjerg, Mette; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
[Skinbjerg, Mette; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA.
[Thorsell, Annika; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
OI Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845
FU NIMH [Z01-MH-002795-07, Z01-MH-002793]; NINDS [NS002263-33]
FX This research was supported by the Intramural Program of NIMH (project
Z01-MH-002795-07 and Z01-MH-002793) and NINDS (project NS002263-33). We
thank Cheryl Morse and Yi Zhang for assistance on radiotracer
production; Jussi Hirvonen for assistance on data analysis; and PMOD
Technologies (Zurich, Switzerland) for providing its image analysis and
modeling software.
NR 33
TC 37
Z9 37
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2010
VL 50
IS 4
BP 1402
EP 1407
DI 10.1016/j.neuroimage.2010.01.055
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 574VY
UT WOS:000276023500007
PM 20097293
ER
PT J
AU Venkatraman, VK
Aizenstein, H
Guralnik, J
Newman, AB
Glynn, NW
Taylor, C
Studenski, S
Launer, L
Pahor, M
Williamson, J
Rosano, C
AF Venkatraman, Vijay K.
Aizenstein, Howard
Guralnik, Jack
Newman, Anne B.
Glynn, Nancy W.
Taylor, Christopher
Studenski, Stephanie
Launer, Lenore
Pahor, Marco
Williamson, Jeff
Rosano, Caterina
TI Executive control function, brain activation and white matter
hyperintensities in older adults (vol 49, pg 3436, 2010)
SO NEUROIMAGE
LA English
DT Correction
C1 [Venkatraman, Vijay K.; Aizenstein, Howard] Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15261 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Guralnik, Jack; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Newman, Anne B.; Glynn, Nancy W.; Taylor, Christopher; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Studenski, Stephanie] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Pahor, Marco] Univ Florida, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA.
[Williamson, Jeff] Wake Forest Univ, Sect Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC 27157 USA.
RP Aizenstein, H (reprint author), UPMC, WPIC, GPN Lab, 3811 Ohara St, Pittsburgh, PA 15213 USA.
EM aizen@pitt.edu
NR 1
TC 0
Z9 0
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2010
VL 50
IS 4
BP 1711
EP 1711
DI 10.1016/j.neuroimage.2010.01.074
PG 1
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 574VY
UT WOS:000276023500039
ER
PT J
AU Adlam, ALR
Malloy, M
Mishkin, M
Vargha-Khadem, F
AF Adlam, Anna-Lynne R.
Malloy, Megan
Mishkin, Mortimer
Vargha-Khadem, Faraneh
TI Dissociation between recognition and recall in developmental amnesia
(vol 47, pg 2207, 2009)
SO NEUROPSYCHOLOGIA
LA English
DT Correction
C1 [Adlam, Anna-Lynne R.; Vargha-Khadem, Faraneh] UCL, Dev Cognit Neurosci Unit, Inst Child Hlth, London WC1N 1EH, England.
[Malloy, Megan; Mishkin, Mortimer] NIMH, Cognit Neurosci Sect, Bethesda, MD 20892 USA.
RP Vargha-Khadem, F (reprint author), UCL, Dev Cognit Neurosci Unit, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England.
EM f.khadem@ich.ucl.ac.uk
RI Adlam, Anna/F-8400-2010; Vargha-Khadem, Faraneh/C-2558-2008;
OI Adlam, Anna/0000-0001-7212-4051
NR 1
TC 0
Z9 0
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD MAY
PY 2010
VL 48
IS 6
BP 1875
EP 1875
DI 10.1016/j.neuropsychologia.2010.03.003
PG 1
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 604FE
UT WOS:000278261900041
ER
PT J
AU Berlin, I
Singleton, EG
Heishman, SJ
AF Berlin, Ivan
Singleton, Edward G.
Heishman, Stephen J.
TI Validity of the 12-item French version of the Tobacco Craving
Questionnaire in treatment-seeking smokers
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKING OUTCOME EXPECTANCIES; NICOTINE DEPENDENCE; INITIAL VALIDATION;
CESSATION; RELIABILITY; WITHDRAWAL; SYMPTOMS; BEHAVIOR; TESTS; URGES
AB The French version of the Tobacco Craving Questionnaire (FTCQ) is a valid and reliable 47-item self-report instrument that assesses tobacco craving in four factors: emotionality, expectancy, compulsivity, and purposefulness. For use in research and clinical settings, we constructed a 12-item version of the FTCQ (FTCQ-12).
The FTCQ-12 was administered to treatment-seeking French smokers (n = 310) enrolled in the Adjustment of DOses of NIcotine in Smoking Cessation (ADONIS) trial. We conducted confirmatory factor analysis (CFA) and examined congruence in factor loadings between the FTCQ and FTCQ-12 to determine the validity and reliability of the FTCQ-12. Measures of tobacco craving, withdrawal, smoking patterns, and smoking history were included to explore the concurrent validity of the FTCQ-12. We used craving scores to distinguish participants who were highly dependent on nicotine from those less dependent on nicotine.
CFA indicated excellent fit for a four-factor model, with congruence coefficients indicating moderate similarity in factor patterns and loadings between the FTCQ and FTCQ-12. Individual factors of the FTCQ-12 correlated positively with smoking history and withdrawal variables. Participants who were highly dependent on nicotine were nearly six times more likely to score > 5 on the General Craving Score (maximum: 7) than those less dependent on nicotine.
Findings suggest that the FTCQ-12 measures the same four factors as the FTCQ and TCQ, and these four constructs have unique properties. The FTCQ-12 yields valid and reliable indices of tobacco craving and has potential clinical utility for rapid assessment of tobacco craving in smokers seeking treatment.
C1 [Berlin, Ivan] Univ Paris 06, Dept Pharmacol, Fac Med, Hop Pitie Salpetriere,INSERM U894, F-75013 Paris, France.
[Singleton, Edward G.] Stevenson Univ, Dept Psychol, Stevenson, MD USA.
[Heishman, Stephen J.] Natl Inst Drug Abuse, Nicotine Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Berlin, I (reprint author), Univ Paris 06, Dept Pharmacol, Fac Med, Hop Pitie Salpetriere,INSERM U894, 47 Bd Hop, F-75013 Paris, France.
EM ivan.berlin@psl.aphp.fr
OI Singleton, Edward G./0000-0003-3442-877X
FU French Ministry of Health Programme Hospitalier de Recherche Clinique
[AOR04001//P040406]; Agence francaise de securite sanitaire des produits
de sante; Convention Pharmacologie Clinique et Therapeutique [RAF02020];
National Institutes of Health; National Institute on Drug Abuse
FX This study was supported by the French Ministry of Health Programme
Hospitalier de Recherche Clinique Loco-regional 2004 (AOR04001//P040406,
registration number: 050558); by the Agence francaise de securite
sanitaire des produits de sante, Convention Pharmacologie Clinique et
Therapeutique 2003, RAF02020 and the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse.
NR 46
TC 16
Z9 16
U1 1
U2 5
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 MAY
PY 2010
VL 12
IS 5
BP 500
EP 507
DI 10.1093/ntr/ntq039
PG 8
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 590PM
UT WOS:000277239300005
PM 20335281
ER
PT J
AU Landolt, K
Ajdacic-Gross, V
Angst, J
Merikangas, KR
Gamma, A
Gutzwiller, F
Rossler, W
AF Landolt, Karin
Ajdacic-Gross, Vladeta
Angst, Jules
Merikangas, Kathleen R.
Gamma, Alex
Gutzwiller, Felix
Roessler, Wulf
TI Smoking and psychiatric disorders: Have subthreshold disorders been
overlooked?
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID UNITED-STATES; EPIDEMIOLOGIC SURVEY; MAJOR DEPRESSION; NICOTINE
DEPENDENCE; CIGARETTE-SMOKING; MENTAL-DISORDERS; BIPOLAR DISORDER;
TOBACCO USE; PREVALENCE; POPULATION
AB Introduction: The association between smoking and mental disorders has been confirmed by several studies using cross-sectional and retrospective designs. The present study illustrates the need for differentiating subthreshold psychiatric disorders in the analysis.
Methods: The analysis is based on cumulative ("lifetime") prevalences of mental disorders and smoking in the Zurich study. This is a longitudinal community study with a stratified sample of 591 participants and six interviews from 1979 to 1999.
Results: The percentage of lifetime smokers in the Zurich study was higher both in persons with a lifetime psychiatric diagnosis (72%) and in persons with subthreshold disorders (60%) than in those without any diagnosis (40%).
Discussion: The association between smoking and mental disorders turned out to be clearly stronger if subthreshold mental disorders were appropriately considered in the analyses. Constructing appropriate reference groups is as crucial for the analysis of mental disorders and their outcomes as constructing adequate diagnostic groups.
C1 [Landolt, Karin; Ajdacic-Gross, Vladeta; Angst, Jules; Gamma, Alex; Roessler, Wulf] Univ Zurich, Hosp Psychiat, Dept Gen & Social Psychiat, Zurich, Switzerland.
[Merikangas, Kathleen R.] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gutzwiller, Felix] Univ Zurich, Inst Social & Prevent Med, Dept Gen & Social Psychiat, CH-8006 Zurich, Switzerland.
RP Landolt, K (reprint author), Psychiat Univ Hosp, Res Unit Clin & Social Psychiat, Militarstr 8 POB 1930, CH-8021 Zurich, Switzerland.
EM klandolt@dgsp.uzh.ch
OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237
FU Swiss National Science Foundation [32-50881.97]; Swiss Cancer
League/Swiss Federation Against Cancer [01649-02-2005]
FX This work was supported by the Swiss National Science Foundation (grant
#32-50881.97)and by the Swiss Cancer League/Swiss Federation Against
Cancer (grant #01649-02-2005).
NR 32
TC 6
Z9 6
U1 2
U2 3
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 MAY
PY 2010
VL 12
IS 5
BP 516
EP 520
DI 10.1093/ntr/ntq023
PG 5
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 590PM
UT WOS:000277239300007
PM 20237120
ER
PT J
AU De Bruyne, S
Wyffels, L
Boos, TL
Staelens, S
Deleye, S
Rice, KC
De Vos, F
AF De Bruyne, Sylvie
Wyffels, Leonie
Boos, Terrence L.
Staelens, Steven
Deleye, Steven
Rice, Kenner C.
De Vos, Filip
TI In vivo evaluation of
[I-123]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidi
ne, an iodinated SPECT tracer for imaging the P-gp transporter
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE P-gp; SPECT; Brain;
[I-123]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidi
ne
ID BLOOD-BRAIN-BARRIER; POSITRON-EMISSION-TOMOGRAPHY; DRUG EFFLUX
TRANSPORTERS; MULTIDRUG-RESISTANCE; GLYCOPROTEIN FUNCTION; ANTIEPILEPTIC
DRUGS; COMPUTED-TOMOGRAPHY; NONHUMAN-PRIMATES; PET; CELLS
AB Introduction: P-glycoprotein (P-gp) is an energy-dependent transporter that contributes to the efflux of a wide range of xenobiotics at the blood brain barrier playing a role in drug-resistance or therapy failure. In this study, we evaluated [I-123]-4-(2-(bis(4-fluorophenyl)methoxy) ethyl)-1-(4-iodobenzyl)piperidine ([I-123]-FMIP) as a novel single photon emission computed tomography (SPECT) tracer for imaging P-gp at the brain in vivo.
Methods: The tissue distribution and brain uptake as well as the metabolic profile of [I-123]-FMIP in wild-type and mdr1a (-/-) mice after pretreatment with physiological saline or cyclosporin A (CsA) (50 mg/kg) was investigated. The influence of increasing doses CsA on brain uptake of [I-123]-FMIP was explored. mu SPECT images of mice brain after injection of 11.1 MBq [I-123]-FMIP were obtained for different treatment strategies thereby using the Milabs U-SPECT-II.
Results: Modulation of P-gp with CsA (50 mg/kg) as well as mdr1a gene depletion resulted in significant increase in cerebral uptake of [I-123]-FMIP with only minor effect on blood activity. [I-123]-FMIP is relative stable in vivo with >80% intact [I-123]-FMIP in brain at 60 min p.i. in the different treatment regiments. A dose-dependent sigmoidal increase in brain uptake of [I-123]-FMIP with increasing doses of CsA was observed. In vivo region of interest-based SPECT measurements correlated well with the observations of the biodistribution studies.
Conclusions: These findings indicate that [I-123]-FMIP can be applied to assess the efficacy of newly developed P-gp modulators. It is also suggested that [I-123]-FMIP is a promising SPECT tracer for imaging P-gp at the blood-brain barrier. (C) 2010 Published by Elsevier Inc.
C1 [De Bruyne, Sylvie; Wyffels, Leonie; De Vos, Filip] Univ Ghent, Lab Radiopharm, B-9000 Ghent, Belgium.
[Boos, Terrence L.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Bethesda, MD USA.
[Boos, Terrence L.; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
[Staelens, Steven; Deleye, Steven] Ghent Univ IBBT, IBITECH Medisip, B-9000 Ghent, Belgium.
RP De Vos, F (reprint author), Univ Ghent, Lab Radiopharm, B-9000 Ghent, Belgium.
EM filipx.devos@ugent.be
RI Staelens, Steven/D-8385-2017;
OI Staelens, Steven/0000-0003-3376-0519; wyffels,
Leonie/0000-0002-5618-8191
NR 53
TC 5
Z9 5
U1 0
U2 5
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 MAY
PY 2010
VL 37
IS 4
BP 469
EP 477
DI 10.1016/j.nucmedbio.2009.10.006
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 596RD
UT WOS:000277701900011
PM 20447559
ER
PT J
AU Law, MP
Wagner, S
Kopka, K
Renner, C
Pike, VW
Schober, O
Schafers, M
AF Law, Marilyn P.
Wagner, Stefan
Kopka, Klaus
Renner, Christiane
Pike, Victor W.
Schober, Otmar
Schaefers, Michael
TI Preclinical evaluation of an F-18-labelled beta(1)-adrenoceptor
selective radioligand based on ICI 89,406
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE [F-18]Fluoroethoxy-ICI 89,406 for PET; beta(1)-radrenoceptor-selective
radioligand; PET radioligand; Myocardial beta(1)-adrenoceptors; Small
animal PET
ID CARDIAC SYMPATHETIC INNERVATION; BETA-ADRENOCEPTOR ANTAGONIST;
POSITRON-EMISSION-TOMOGRAPHY; HEART-FAILURE; IN-VIVO; RAT-HEART;
PET-RADIOLIGANDS; DOWN-REGULATION; BINDING-SITES; AFFINITY
AB Purpose: Radioligand binding studies indicate a down-regulation of myocardial beta(1)-adrenoceptors (beta(1)-AR) in cardiac disease which may or may not be associated with a decrease in beta(2)-ARs. We have chosen ICI 89,406, a beta(1)-selective AR antagonist, as the lead structure to develop new beta(1)-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI).
Methods: (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-[4-(2-[F-18]fluoro-ethoxy)-phenyl]-urea ((S)-[E-18]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[F-18]F-ICT into adult CD1 mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine.
Results: The heart was visualised with PET after injection of (S)-[E-18]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[F-18]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (beta(1)-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[F-18]F-ICI and radiometabolites accumulated in urine.
Conclusions: Myocardial uptake of (S)-[F-18]F-ICI after intravenous injection was mainly at sites unrelated to beta(1)-ARs. (S)-[F-18]F-ICI is not a suitable beta(1)-selective-AR radioligand for PET. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Law, Marilyn P.; Wagner, Stefan; Kopka, Klaus; Renner, Christiane; Schober, Otmar] Univ Hosp Munster, Dept Nucl Med, D-48149 Munster, Germany.
[Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Law, Marilyn P.; Schaefers, Michael] European Inst Mol Imaging, D-48149 Munster, Germany.
RP Law, MP (reprint author), Univ Hosp Munster, Dept Nucl Med, D-48149 Munster, Germany.
EM mplaw@uni-muenster.de
FU Deutsche Forschungsgemeinschaft (DFG); Sonderforschungsbereich 656 MoBil
Munster, Germany; Interdisciplinary Clinical Research Centre, Minister,
Germany; EC [LSHB-CT-2005-512146]; National Institutes of Health, USA
FX This work was supported by grants from the Deutsche
Forschungsgemeinschaft (DFG), Sonderforschungsbereich 656 MoBil Munster,
Germany (projects AS and C6), by the Interdisciplinary Clinical Research
Centre, Minister (IZKF, core unit SmAP), Germany, and by the EC -
FP6-project DiMI (WP 11.1), LSHB-CT-2005-512146. Dr. V.W. Pike is
supported by the Intramural Research Program of the National Institutes
of Health (the National Institute of Mental Health), USA.
NR 43
TC 5
Z9 5
U1 0
U2 1
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 MAY
PY 2010
VL 37
IS 4
BP 517
EP 526
DI 10.1016/j.nucmedbio.2010.01.004
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 596RD
UT WOS:000277701900016
PM 20447564
ER
PT J
AU Speina, E
Dawut, L
Hedayati, M
Wang, ZM
May, A
Schwendener, S
Janscak, P
Croteau, DL
Bohr, VA
AF Speina, Elzbieta
Dawut, Lale
Hedayati, Mohammad
Wang, ZhengMing
May, Alfred
Schwendener, Sybille
Janscak, Pavel
Croteau, Deborah L.
Bohr, Vilhelm A.
TI Human RECQL5 beta stimulates flap endonuclease 1
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BASE EXCISION-REPAIR; DNA-POLYMERASE-BETA; ROTHMUND-THOMSON-SYNDROME;
SYNDROME PROTEIN; REPLICATION FORK; HUMAN RECQ5-BETA; WERNER-SYNDROME;
POLY(ADP-RIBOSE) POLYMERASE-1; ESCHERICHIA-COLI; HOMOLOGOUS
RECOMBINATION
AB Human RECQL5 is a member of the RecQ helicase family which is implicated in genome maintenance. Five human members of the family have been identified; three of them, BLM, WRN and RECQL4 are associated with elevated cancer risk. RECQL1 and RECQL5 have not been linked to any human disorder yet; cells devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physical and functional interaction of the large isomer of RECQL5, RECQL5 beta, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5 beta dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5 beta and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests that the ability of RecQ helicases to stimulate FEN1 may be a general feature of this class of enzymes. This could indicate a common role for the RecQ helicases in the processing of oxidative DNA damage.
C1 [Speina, Elzbieta; Dawut, Lale; Hedayati, Mohammad; Wang, ZhengMing; May, Alfred; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, NIH, Baltimore, MD 21224 USA.
[Speina, Elzbieta] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland.
[Schwendener, Sybille; Janscak, Pavel] Univ Zurich, Inst Mol Canc Res, CH-8006 Zurich, Switzerland.
RP Bohr, VA (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
RI Janscak, Pavel/G-6189-2014
FU National Institutes of Health; National Institute on Aging [Z01
AG000726-16]; Swiss National Science Foundation
FX FUNDING; Intramural Research Program of the National Institutes of
Health; National Institute on Aging, annual report Z01 AG000726-16;
Swiss National Science Foundation (to S. S., P.J.). Funding for open
access charge: National Institutes of Health.
NR 58
TC 13
Z9 15
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY
PY 2010
VL 38
IS 9
BP 2904
EP 2916
DI 10.1093/nar/gkp1217
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 600NV
UT WOS:000277994600020
PM 20081208
ER
PT J
AU Grady, PA
AF Grady, Patricia A.
TI Translational research and nursing science
SO NURSING OUTLOOK
LA English
DT News Item
C1 [Grady, Patricia A.] NINR, Bethesda, MD 20892 USA.
RP Grady, PA (reprint author), Care Of Bingham RJ, NINR, Off Sci Policy & Publ Liaison, 31 Ctr Dr,MSC-2178,Bldg 31,Room 5B-10, Bethesda, MD 20892 USA.
NR 7
TC 17
Z9 17
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD MAY-JUN
PY 2010
VL 58
IS 3
BP 164
EP 166
DI 10.1016/j.outlook.2010.01.001
PG 3
WC Nursing
SC Nursing
GA 610WN
UT WOS:000278769800010
PM 20494692
ER
PT J
AU McLaughlin, TM
Liu, T
Yee, G
Abbasi, F
Lamendola, C
Reaven, GM
Tsao, P
Cushman, SW
Sherman, A
AF McLaughlin, Tracey M.
Liu, T.
Yee, Gail
Abbasi, F.
Lamendola, C.
Reaven, G. M.
Tsao, P.
Cushman, S. W.
Sherman, A.
TI Pioglitazone Increases the Proportion of Small Cells in Human Abdominal
Subcutaneous Adipose Tissue
SO OBESITY
LA English
DT Article
ID MEDIATED GLUCOSE DISPOSAL; ACTIVATED RECEPTOR-GAMMA; INSULIN SUPPRESSION
TEST; TYPE-2 DIABETIC-PATIENTS; BODY-FAT DISTRIBUTION; PREADIPOCYTE
DIFFERENTIATION; ADIPOCYTE DIFFERENTIATION; IN-VIVO; RESISTANCE;
MELLITUS
AB Rodent and in vitro studies suggest that thiazolidinediones promote adipogenesis but there are few studies in humans to corroborate these findings. The purpose of this study was to determine whether pioglitazone stimulates adipogenesis in vivo and whether this process relates to improved insulin sensitivity. To test this hypothesis, 12 overweight/obese nondiabetic, insulin-resistant individuals underwent biopsy of abdominal subcutaneous adipose tissue at baseline and after 12 weeks of pioglitazone treatment. Cell size distribution was determined via the Multisizer technique. Insulin sensitivity was quantified at baseline and postpioglitazone by the modified insulin suppression test. Regional fat depots were quantified by computed tomography (CT). Insulin resistance (steady-state plasma insulin and glucose (SSPG)) decreased following pioglitazone (P < 0.001). There was an increase in the ratio of small-to-large cells (1.16 +/- 0.44 vs. 1.52 +/- 0.66, P = 0.03), as well as a 25% increase in the absolute number of small cells (P = 0.03). The distribution of large cell diameters widened (P = 0.009), but diameter did not increase in the case of small cells. The increase in proportion of small cells was associated with the degree to which insulin resistance improved (r = -0.72, P = 0.012). Visceral abdominal fat decreased (P = 0.04), and subcutaneous abdominal (P = 0.03) and femoral fat (P = 0.004) increased significantly. Changes in fat volume were not associated with SSPG change. These findings demonstrate a clear effect of pioglitazone on human subcutaneous adipose cells, suggestive of adipogenesis in abdominal subcutaneous adipose tissue, as well as redistribution of fat from visceral to subcutaneous depots, highlighting a potential mechanism of action for thiazolidinediones. These findings support the hypothesis that defects in subcutaneous fat storage may underlie obesity-associated insulin resistance.
C1 [McLaughlin, Tracey M.; Yee, Gail; Abbasi, F.; Lamendola, C.; Reaven, G. M.; Tsao, P.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Liu, T.; Cushman, S. W.; Sherman, A.] NIDDK, NIH, Bethesda, MD USA.
RP McLaughlin, TM (reprint author), Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
EM tmclaugh@stanford.edu
FU NIH/NIDDK [1 R01 DK071309-01, 5K23 RR16071, 1RO1 DK071333]; NIH [RR
000070]; NIDDK; Takeda Pharmaceuticals
FX This work was supported by study grants: NIH/NIDDK 1 R01 DK071309-01,
5K23 RR16071, 1RO1 DK071333, NIH RR 000070, the NIDDK Intramural
Research Program, and Takeda Pharmaceuticals.
NR 31
TC 23
Z9 23
U1 0
U2 2
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 MAY
PY 2010
VL 18
IS 5
BP 926
EP 931
DI 10.1038/oby.2009.380
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 590OA
UT WOS:000277234800013
PM 19910937
ER
PT J
AU Tadros, TM
Massaro, JM
Rosito, GA
Hoffmann, U
Vasan, RS
Larson, MG
Keaney, JF
Lipinska, I
Meigs, JB
Kathiresan, S
O'Donnell, CJ
Fox, CS
Benjamin, EJ
AF Tadros, Thomas M.
Massaro, Joseph M.
Rosito, Guido A.
Hoffmann, Udo
Vasan, Ramachandran S.
Larson, Martin G.
Keaney, John F., Jr.
Lipinska, Izabella
Meigs, James B.
Kathiresan, Sekar
O'Donnell, Christopher J.
Fox, Caroline S.
Benjamin, Emelia J.
TI Pericardial Fat Volume Correlates With Inflammatory Markers: The
Framingham Heart Study
SO OBESITY
LA English
DT Article
ID EPICARDIAL ADIPOSE-TISSUE; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN;
METABOLIC SYNDROME; INSULIN-RESISTANCE; RISK-FACTORS;
CARDIOVASCULAR-DISEASE; MAJOR DETERMINANT; OXIDATIVE STRESS; VISCERAL
FAT
AB The objective of this study was to determine whether systemic inflammatory and oxidative stress marker concentrations correlate with pericardial and intrathoracic fat volumes. Participants of the Framingham Offspring Study (n = 1,175, 53% women, mean age 59 +/- 9 years) had pericardial and intrathoracic fat volumes assessed by multidetector computed tomography (MDCT) scans, and provided fasting blood and urine samples to measure concentrations of 14 inflammatory markers: C-reactive protein (CRP), interleukin-6, monocyte chemoattractant protein-1 (MCP-1), CD40 ligand, fibrinogen, intracellular adhesion molecule-1, lipoprotein-associated phospholipase A 2 activity and mass, myeloperoxidase, osteoprotegerin, P-selectin, tumor necrosis factor-a, tumor necrosis factor receptor-2, and urinary isoprostanes. Multivariable linear regression models were used to determine the association of log-transformed inflammatory marker concentrations with fat volumes, using fat volume as the dependent variable. Due to smaller sample sizes, models were rerun after adding urinary isoprostanes (n = 961) and tumor necrosis factor-a (n = 813) to the marker panel. Upon backward elimination, four of the biomarkers correlated positively with each fat depot: CRP (P < 0.0001 for each fat depot), interleukin-6 (P < 0.05 for each fat depot), MCP-1 (P < 0.01 for each fat depot), and urinary isoprostanes (P < 0.01 for pericardial fat; P < 0.001 for intrathoracic fat). Even after adjusting for BMI, waist circumference (WC), and abdominal visceral fat, CRP (P = 0.0001) and urinary isoprostanes (P = 0.02) demonstrated significant positive associations with intrathoracic fat, but not with pericardial fat. Multiple markers of inflammation and oxidative stress correlated with pericardial and intrathoracic fat volumes, extending the known association between regional adiposity and inflammation and oxidative stress.
C1 [Tadros, Thomas M.; Massaro, Joseph M.; Vasan, Ramachandran S.; Larson, Martin G.; O'Donnell, Christopher J.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Tadros, Thomas M.; Benjamin, Emelia J.] Boston Univ, Sch Med, Div Cardiol, Boston Univ Med Ctr, Boston, MA 02118 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Rosito, Guido A.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Cardiol, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Prevent Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02118 USA.
[Keaney, John F., Jr.; Lipinska, Izabella] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA.
[Meigs, James B.; Benjamin, Emelia J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02115 USA.
[Kathiresan, Sekar; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Boston, MA USA.
EM emelia@bu.edu
OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National
Institute of Health, National Center for Research Resources
[RO1-HL076784, RO1-HL064753, R01-AG028321]; General Clinical Research
Centers [M01-RR-01066]; American Diabetes Association; National
Institute of Health/National Heart, Lung, and Blood Institute
[2K24HL04334]; NIDDK [K24 DK080140]
FX Lipoprotein-associated phospholipase A2 activity was measured by
GlaxoSmithKline and lipoprotein-associated phospholipase A2 mass was
measured by diaDexus without cost to the Framingham Heart Study. 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 (E.J.B), National Institute of Health, National Center
for Research Resources, General Clinical Research Centers Program (grant
number M01-RR-01066), and by a Career Development Award from the
American Diabetes Association (J.B.M.). R. S. V. is partially supported
by 2K24HL04334 (National Institute of Health/National Heart, Lung, and
Blood Institute). J.B.M. was supported by NIDDK K24 DK080140.
NR 39
TC 39
Z9 40
U1 0
U2 1
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 MAY
PY 2010
VL 18
IS 5
BP 1039
EP 1045
DI 10.1038/oby.2009.343
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 590OA
UT WOS:000277234800031
PM 19875999
ER
PT J
AU Bosquet, JG
Terstriep, SA
Cliby, WA
Brown-Jones, M
Kaur, JS
Podratz, KC
Keeney, GL
AF Bosquet, Jesus Gonzalez
Terstriep, Shelby A.
Cliby, William A.
Brown-Jones, Monica
Kaur, Judith S.
Podratz, Karl C.
Keeney, Gary L.
TI The Impact of Multimodal Therapy on Survival for Uterine Carcinosarcomas
EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Bosquet, Jesus Gonzalez] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
Mayo Clin, Dept Obstet & Gynecol, Div Gynecol Oncol, Rochester, MN USA.
Mayo Clin, Dept Anat Pathol, Rochester, MN USA.
RP Bosquet, JG (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD MAY
PY 2010
VL 65
IS 5
BP 313
EP 314
DI 10.1097/OGX.0b013e3181e39c85
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 619BA
UT WOS:000279400600015
ER
PT J
AU Asnaghi, L
Vass, WC
Quadri, R
Day, PM
Qian, X
Braverman, R
Papageorge, AG
Lowy, DR
AF Asnaghi, L.
Vass, W. C.
Quadri, R.
Day, P. M.
Qian, X.
Braverman, R.
Papageorge, A. G.
Lowy, D. R.
TI E-cadherin negatively regulates neoplastic growth in non-small cell lung
cancer: role of Rho GTPases
SO ONCOGENE
LA English
DT Article
DE E-cadherin; NSCLC; tumorigenesis; cell migration; Rho-family GTPases
ID BETA-CATENIN; FACTOR RECEPTOR; FAMILY GTPASES; BREAST-CANCER; ACTIVATING
PROTEIN; REDUCED EXPRESSION; TISSUE MICROARRAY; TUMOR PROGRESSION;
TYROSINE KINASES; ALPHA-CATENIN
AB Non-small cell lung cancers (NSCLC) that express the cell surface adhesion protein E-cadherin may carry a better prognosis than E-cadherin-negative tumors. Here, we found substantial inhibition of anchorage-independent growth in soft agar and cell migration in each of four NSCLC lines stably transfected with E-cadherin. The inhibitory effects were independent of the EGFR and beta-catenin/Wnt-signaling pathways. However, E-cadherin expression was associated with an adhesion-dependent reduction in the activity of Rho family proteins, RhoA in two lines and Cdc42 in the other two. The reduction of RhoA activity was dependent on DLC-1 Rho-GAP and p190 Rho-GAP and associated with an increase in a membrane-associated p190 Rho-GAP/p120 Ras-GAP complex. In parental cells with high levels of RhoAGTP, siRNA-mediated knock-down of RhoA reduced cell migration and agar growth in a manner analogous to E-cadherin. In parental cells with high levels of Cdc42-GTP, transfection of a Cdc42 dominant-negative mutant reduced cell growth and migration similarly to cells expressing E-cadherin. Thus, E-cadherin can negatively regulate cell proliferation and migration in NSCLC by reducing the level of the predominant active form of Rho family protein, RhoA or Cdc42. These proteins can be considered downstream effectors of E-cadherin and might represent therapeutic targets in some NSCLC. Oncogene (2010) 29, 2760-2771; doi: 10.1038/onc. 2010.39; published online 15 March 2010
C1 [Asnaghi, L.; Vass, W. C.; Quadri, R.; Day, P. M.; Qian, X.; Braverman, R.; Papageorge, A. G.; Lowy, D. R.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 37 Convent Dr MSC 4264,Bldg 37,Rm 4106,37 Convent, Bethesda, MD 20892 USA.
EM lowyd@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX We thank Drs Margaret Wheelock, Wen Jin Wu, Dianne Hirsch and Silvio
Gutkind for providing plasmids, Drs Curt Harris and Terry Moody for
providing NSCLC cell lines, Dr Cynthia Masison and Mike Radanovich for
technical assistance and Dr Giovanna Tosato for helpful discussions.
This research has been supported by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 66
TC 29
Z9 30
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAY
PY 2010
VL 29
IS 19
BP 2760
EP 2771
DI 10.1038/onc.2010.39
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 595DW
UT WOS:000277591900002
PM 20228844
ER
PT J
AU Abrams, J
Erwin, R
Fyfe, G
Schilsky, RL
AF Abrams, Jeffrey
Erwin, Robert
Fyfe, Gwen
Schilsky, Richard L.
TI Data Submission Standards and Evidence Requirements
SO ONCOLOGIST
LA English
DT Article
C1 [Abrams, Jeffrey] NCI, Bethesda, MD 20892 USA.
[Erwin, Robert] Marti Nelson Canc Fdn, Vacaville, CA USA.
[Schilsky, Richard L.] Univ Chicago, Chicago, IL 60637 USA.
RP Abrams, J (reprint author), NCI, Bethesda, MD 20892 USA.
NR 3
TC 3
Z9 3
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAY
PY 2010
VL 15
IS 5
BP 488
EP 491
DI 10.1634/theoncologist.2009-0260
PG 4
WC Oncology
SC Oncology
GA 599NC
UT WOS:000277918900007
PM 20489185
ER
PT J
AU Amit, O
Bushnell, W
Dodd, L
Roach, N
Sargent, D
AF Amit, Ohad
Bushnell, Will
Dodd, Lori
Roach, Nancy
Sargent, Daniel
TI Blinded Independent Central Review of the Progression-Free Survival
Endpoint
SO ONCOLOGIST
LA English
DT Article
ID TRIALS
C1 [Amit, Ohad; Bushnell, Will] GlaxoSmithKline Inc, Collegeville, PA USA.
[Dodd, Lori] NIAID, Bethesda, MD 20892 USA.
[Roach, Nancy] Colorectal Canc Coalit, Alexandria, VA USA.
[Sargent, Daniel] Mayo Clin, Rochester, MN USA.
RP Amit, O (reprint author), GlaxoSmithKline Inc, Collegeville, PA USA.
OI Sargent, Daniel/0000-0002-2684-4741
NR 5
TC 15
Z9 15
U1 1
U2 1
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAY
PY 2010
VL 15
IS 5
BP 492
EP 495
DI 10.1634/theoncologist.2009-0261
PG 4
WC Oncology
SC Oncology
GA 599NC
UT WOS:000277918900008
PM 20489186
ER
PT J
AU Clark, A
Ellis, M
Erlichman, C
Lutzker, S
Zwiebel, J
AF Clark, Adam
Ellis, Matthew
Erlichman, Charles
Lutzker, Stuart
Zwiebel, James
TI Development of Rational Drug Combinations with Investigational Targeted
Agents
SO ONCOLOGIST
LA English
DT Article
C1 [Clark, Adam] Lance Armstrong Fdn, Austin, TX USA.
[Ellis, Matthew] Washington Univ, St Louis, MO USA.
[Erlichman, Charles] Mayo Clin, Rochester, MN USA.
[Lutzker, Stuart] Genentech Inc, San Francisco, CA 94080 USA.
[Zwiebel, James] NCI, Bethesda, MD 20892 USA.
RP Clark, A (reprint author), Lance Armstrong Fdn, Austin, TX USA.
FU Novartis; AstraZeneca
FX Disclosures: Adam Clark: Employment: Lance Armstrong Foundation;
Consultant/advisory role: American Society of Health Information
Managers; Honoraria: McKesson, Cancer Support Community. Matthew Ellis:
Employment: Bioclassifier LLC; Consultant/advisory role: ASCO, CALGB,
ACOSOS, Novartis, Pfizer, AstraZeneca, Merck; Honoraria: Novartis,
GlaxoSmithKline, AstraZeneca, Pfizer; Research funding/contracted
research: Novartis, AstraZeneca; Ownership interest: Bioclassifier LLC.
Charles Erlichman: None; Stuart Lutzker: Employment: Genentech; James
Zwiebel: None.
NR 2
TC 3
Z9 3
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAY
PY 2010
VL 15
IS 5
BP 496
EP 499
DI 10.1634/theoncologist.2009-0262
PG 4
WC Oncology
SC Oncology
GA 599NC
UT WOS:000277918900009
PM 20489187
ER
PT J
AU Roy, D
Arason, GA
Chowdhury, B
Mitra, A
Calaf, GM
AF Roy, D.
Arason, G. A.
Chowdhury, B.
Mitra, A.
Calaf, G. M.
TI Profiling of cell cycle genes of breast cells exposed to etodolac
SO ONCOLOGY REPORTS
LA English
DT Article
DE cell cycle; breast cells; etodolac
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CANCER-CELLS; EXPRESSION;
RADIATION; LINE; REPLICATION; MECHANISMS; PREVENTION; INHIBITORS;
P27(KIP1)
AB Breast cancer represents the second leading cause of cancer-related deaths in the world. There is increasing evidence that perturbation of cell cycle regulation is an important contributing factor to various cancer progression stages. There are key checkpoints in the cell cycle involving various regulatory proteins. The relationship between these cell cycle regulatory proteins and cell cycle arrest by cyclooxygenase (COX) inhibitors during neoplastic progression remains largely unknown. Preclinical studies and epidemiological investigations have consistently shown that nonsteroidal anti-inflammatory drugs have some anti-proliferative and anti-oxidative stress response on various tumors. In this study, the effect of etodolac, a 1,8-diethyl-1,3,4,9-tetrahydropyrano (3,4-beta) indole-1-acetic acid on signaling pathways was investigated by examining the differential expression of various cell cycle regulatory protein genes. A human cell cycle gene array was used to profile the expression of 96 genes involved in the cell cycle regulation. Differentially expressed genes were highly altered by etodolac treatment. Twenty-six genes were up- and 20 down-regulated with 0.5 and 2 mM etodolac treatment. respectively. Seven genes (ATM, BAX, CCNA2, CDC27, RAD50 and p21) were prominently altered, and six (ATM, CCND2, CCNF, CDC20, CDK1A and RAD50) were commonly altered with both concentrations. This finding indicated that etodolac could play a critical role on cancer cells by inducing cell death.
C1 [Roy, D.] CUNY, Dept Nat Sci, Hostos Coll, Bronx, NY 10451 USA.
[Roy, D.; Arason, G. A.] Manhattan Coll, Grad Biotechnol Program, Riverdale, NY USA.
[Chowdhury, B.] NCI, Human Retrovirus Sect, Vaccine Branch, NIH, Frederick, MD 21701 USA.
[Chowdhury, B.] Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD USA.
[Mitra, A.] Coll Mt St Vincent, Dept Chem, Riverdale, NY USA.
[Calaf, G. M.] Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA.
[Calaf, G. M.] Univ Tarapaca, Inst Alta Invest, Arica, Chile.
RP Roy, D (reprint author), CUNY, Dept Nat Sci, Hostos Coll, Hostos Coll Campus,A-507E,475 Grand Concourse, Bronx, NY 10451 USA.
EM droy@hostos.cuny.edu
FU Manhattan College of New York
FX This study was conducted as part of a Master's Degree thesis (GAA) and
it was funded by the Graduate Biotechnology Program of the Manhattan
College of New York. Thanks are given to FONDECYT 1080482 (GMC), CUNY
Research Release Time (DR). The secretarial assistance of Danissa
Barahona is greatly appreciated. We also thank Convenio de Desempeno
UTA/MESESUP2 from Universidad de Tarapaca, Arica, Chile.
NR 43
TC 4
Z9 4
U1 3
U2 3
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD MAY
PY 2010
VL 23
IS 5
BP 1383
EP 1391
DI 10.3892/or_00000775
PG 9
WC Oncology
SC Oncology
GA 588MR
UT WOS:000277075100027
PM 20372855
ER
PT J
AU Demchenko, YN
Kuehl, WM
AF Demchenko, Yulia N.
Kuehl, W. Michael
TI A critical role for the NFkB pathway in multiple myeloma
SO ONCOTARGET
LA English
DT Article
DE Multiple myeloma; NFkB; mutations; cancer; chemotherapy; leukemia; drug
resistance
ID B-CELL-LYMPHOMA; CLASSICAL HODGKIN LYMPHOMA; IN-SITU HYBRIDIZATION;
KAPPA-B; THERAPEUTIC IMPLICATIONS; WALDENSTROMS MACROGLOBULINEMIA;
MOLECULAR CLASSIFICATION; SIGNALING PATHWAY; HUMAN CANCER; ACTIVATION
AB NFkB transcription factors play a key role in the survival and proliferation of many kinds of B-cell tumors, including multiple myeloma (MM). It was shown that NFkB activation in MM tumors results mainly from extrinsic signaling by APRIL and BAFF ligands that stimulate receptors on normal plasma cells as well as on pre-malignant monoclonal gammopathy of undetermined significance (MGUS) and MM tumors. However, the mutations that occur during MM progression and that constitutively activate NFkB would be expected to decrease dependence of tumor cells on the bone marrow microenvironment. These mutations can activate the classical or alternative NFkB pathways selectively, but usually both pathways are activated in MM. Significantly, activation of either NFkB pathway leads to a similar response of MM cell lines. This frequent activation of the alternative pathway distinguishes MM from other B-cell tumors, which more frequently have mutations that are predicted to activate only the classical NFkB pathway. Given the strong dependence of MGUS and MM tumors on NFkB pathway activation, inhibition by a combination of targeting extrinsic signaling plus both NFkB pathways appears to be an attractive therapeutic approach in MM tumors.
C1 [Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, Bethesda, MD 20889 USA.
RP Kuehl, WM (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, Bldg 8,Room 5101, Bethesda, MD 20889 USA.
EM wmk@helix.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The authors also
acknowledge collaborations and helpful discussions with L.M. Staudt,
C.M. Annunziata, R.E. Davis, P.L. Bergsagel, J.J. Keats; and also
discussions with S. Vallabhapurapu.
NR 75
TC 58
Z9 63
U1 3
U2 12
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY
PY 2010
VL 1
IS 1
BP 59
EP 68
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 801XY
UT WOS:000293475100009
PM 20890394
ER
PT J
AU Aiello, LP
Edwards, AR
Beck, RW
Bressler, NM
Davis, MD
Ferris, F
Glassman, AR
Ip, MS
Miller, KM
AF Aiello, Lloyd Paul
Edwards, Allison R.
Beck, Roy W.
Bressler, Neil M.
Davis, Matthew D.
Ferris, Frederick
Glassman, Adam R.
Ip, Michael S.
Miller, Kellee M.
CA Diabet Retinopathy Clinical Res
TI Factors Associated with Improvement and Worsening of Visual Acuity 2
Years after Focal/Grid Photocoagulation for Diabetic Macular Edema
SO OPHTHALMOLOGY
LA English
DT Article
ID INTRAVITREAL TRIAMCINOLONE; RETINOPATHY; TRIAL; PROGRESSION
AB Purpose: To identify factors associated with the visual acuity outcome after focal/grid photocoagulation for diabetic macular edema (DME) among eyes randomized to the focal/grid photocoagulation treatment group within the Diabetic Retinopathy Clinical Research Network (DRCR.net) trial comparing triamcinolone with focal/grid laser.
Design: Multicenter, randomized, clinical trial.
Participants: Three hundred thirty eyes with DME assigned to the focal/grid photocoagulation group, visual acuity 20/40 to 20/320, and optical coherence tomography (OCT) central subfield thickness >= 250 microns.
Methods: Eyes were treated with a protocol-defined photocoagulation technique, which was repeated at 4-month intervals for persistent or recurrent edema. Separate logistic regression models were used to evaluate the associations of demographic, clinical, OCT, and fundus photographic variables with visual acuity improvement or worsening of >= 10 letters from baseline to 2 years. The association of the initial visual acuity outcome after treatment with the subsequent visual acuity course also was evaluated.
Main Outcome Measures: Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method.
Results: Worse baseline visual acuity was the only factor found to be associated with more frequent visual acuity improvement (P<0.001), and both greater baseline OCT-measured retinal volume (P = 0.001) and better baseline visual acuity (P = 0.009) were found to be associated with more frequent visual acuity worsening. Visual acuity outcomes were similar in eyes with and without prior macular or panretinal photocoagulation. The initial visual acuity outcome at 4 months was not generally predictive of the subsequent course. Many eyes that worsened >= 10 letters from baseline to 4 months subsequently improved, and many eyes that initially improved, subsequently worsened.
Conclusions: At this time, focal/grid photocoagulation remains the standard management for DME and these results do not alter this paradigm.
C1 [Ferris, Frederick] NEI, NIH, Bethesda, MD 20892 USA.
[Ip, Michael S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Edwards, Allison R.; Beck, Roy W.; Glassman, Adam R.; Miller, Kellee M.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA.
[Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA.
RP Edwards, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM drcrstat1@jaeb.org
FU Allergan; National Eye Institute; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health; U.S.
Department of Health and Human Services [EY14231, EY14269, EY14229]
FX Dr. Michael S. Ip receives consultant fees for QLT, Sirion Therapeutics,
Heidelberg Engineering. He also receives financial support from
Allergan. However, we do not believe that any of these constitutes a
financial conflict of interest for this manuscript.; Supported through a
cooperative agreement from the National Eye Institute and the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, U.S. Department of Health and Human Services
EY14231, EY14269, EY14229.
NR 14
TC 37
Z9 38
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAY
PY 2010
VL 117
IS 5
BP 946
EP 953
DI 10.1016/j.ophtha.2009.10.002
PG 8
WC Ophthalmology
SC Ophthalmology
GA 590XM
UT WOS:000277261800015
PM 20122739
ER
PT J
AU Gurkan, I
Ranganathan, A
Yang, X
Horton, WE
Todman, M
Huckle, J
Pleshko, N
Spencer, RG
AF Gurkan, I.
Ranganathan, A.
Yang, X.
Horton, W. E., Jr.
Todman, M.
Huckle, J.
Pleshko, N.
Spencer, R. G.
TI Modification of osteoarthritis in the guinea pig with pulsed
low-intensity ultrasound treatment
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Article
DE Osteoarthritis; Ultrasound; Cartilage; Cartilage repair; Cartilage
degeneration
ID TISSUE-ENGINEERED CARTILAGE; PLACEBO-CONTROLLED TRIALS; AGGRECAN
GENE-EXPRESSION; DOUBLE-BLIND TRIAL; THERAPEUTIC ULTRASOUND;
ELECTROMAGNETIC-FIELDS; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE;
IN-VITRO; MATRIX PRODUCTION
AB Objective: The Hartley guinea pig develops articular cartilage degeneration similar to that seen in idiopathic human osteoarthritis (OA). We investigated whether the application of pulsed low-intensity ultrasound (PLIUS) to the Hartley guinea pig joint would prevent or attenuate the progression of this degenerative process.
Methods: Treatment of male Hartley guinea pigs was initiated at the onset of degeneration (8 weeks of age) to assess the ability of PLIUS to prevent OA, or at a later age (12 months) to assess the degree to which PLIUS acted to attenuate the progression of established disease. PLIUS (30 mW/cm(2)) was applied to stifle joints for 20 min/day over periods ranging from 3 to 10 months, with contralateral limbs serving as controls. Joint cartilage histology was graded according to a modified Mankin scale to evaluate treatment effect. Immunohistochemical staining for interleukin-1 receptor antagonist (IL-1ra), matrix metalloproteinase (MMP)-3, MMP-13, and transforming growth factor (TGF)-beta 1 was performed on the cartilage to evaluate patterns of expression of these proteins.
Results: PLIUS did not fully prevent cartilage degeneration in the prevention groups, but diminished the severity of the disease, with the treated joints showing markedly decreased surface irregularities and a much smaller degree of loss of matrix staining as compared to controls. PLIUS also attenuated disease progression in the groups with established disease, although to a somewhat lesser extent as compared to the prevention groups. Immunohistochemical staining demonstrated a markedly decreased degree of TGF-beta 1 production in the PLIUS-treated joints. This indicates less active endogenous repair, consistent with the marked reduction in cartilage degradation.
Conclusions: PLIUS exhibits the ability to attenuate the progression of cartilage degeneration in an animal model of idiopathic human OA. The effect was greater in the treatment of early, rather than established, degeneration. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
C1 [Spencer, R. G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Yang, X.] Hosp Special Surg, New York, NY 10021 USA.
[Horton, W. E., Jr.] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Rootstown, OH 44272 USA.
[Todman, M.; Huckle, J.] Smith & Nephew Grp Res Ctr, York, N Yorkshire, England.
[Pleshko, N.] Temple Univ, Philadelphia, PA 19122 USA.
RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, Intramural Res Program, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
FU Smith and Nephew, Ltd.; NIH, National Institute on Aging; Smith and
Nephew Ltd., London, UK; NIH [R01 EB000744]
FX Drs Huckle and Todman are employees of Smith and Nephew, Ltd., which
provided partial sponsorship for this study.; We thank Kenneth Fishbein
for his interest and comments. This research was supported in part by
the Intramural Research Program of the NIH, National Institute on Aging,
by Smith and Nephew Ltd., London, UK, and by NIH R01 EB000744 (NP).
NR 64
TC 21
Z9 25
U1 2
U2 7
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD MAY
PY 2010
VL 18
IS 5
BP 724
EP 733
DI 10.1016/j.joca.2010.01.006
PG 10
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 602YS
UT WOS:000278175600018
PM 20175971
ER
PT J
AU Keyak, JH
Sigmarsdottir, A
Karlsdottir, GS
Sigurdsson, S
Eiriksdottir, G
Lu, Y
Zhao, S
Harris, T
Sigurdsson, G
Gudnason, V
Lang, TF
AF Keyak, J. H.
Sigmarsdottir, A.
Karlsdottir, G. S.
Sigurdsson, S.
Eiriksdottir, G.
Lu, Y.
Zhao, S.
Harris, T.
Sigurdsson, G.
Gudnason, V.
Lang, T. F.
TI PROXIMAL FEMORAL STRENGTH FOR PREDICTING HIP FRACTURE IN MEN AND WOMEN:
THE AGES-REYKJAVIK STUDY
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT IOF World Congress on Osteoporosis/10th European Congress on Clinical
and Economic Aspects of Osteoporosis and Osteoarthritis
CY MAY 05-08, 2010
CL Florence, ITALY
C1 [Keyak, J. H.] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA.
[Sigmarsdottir, A.; Karlsdottir, G. S.; Sigurdsson, S.; Eiriksdottir, G.; Sigurdsson, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Lu, Y.; Zhao, S.; Lang, T. F.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Harris, T.] NIA, Bethesda, MD 20892 USA.
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAY
PY 2010
VL 21
SU 1
BP 13
EP 13
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 591KN
UT WOS:000277299400026
ER
PT J
AU Olivo-Marston, S
Graubard, BI
Visvanathan, K
Forman, MR
AF Olivo-Marston, Susan
Graubard, Barry I.
Visvanathan, Kala
Forman, Michele R.
TI Gender-specific differences in birthweight and the odds of puberty:
NHANES III, 1988-94
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE puberty; birthweight; childhood BMI; NHANES
ID BREAST-CANCER RISK; NUTRITION EXAMINATION SURVEY; MATERNAL
CIGARETTE-SMOKING; PREGNANCY-RELATED EVENTS; TESTICULAR CANCER; ADULT
DISEASE; US GIRLS; GENETIC SUSCEPTIBILITY; DEVELOPMENTAL ORIGINS;
NATIONAL-HEALTH
AB The association between birthweight and the odds ratio ( OR) of pubertal status in girls aged between 8 and 11 and in boys aged between 8 and 12 was examined using the 1988-94 Third National Health and Nutrition Examination Survey ( NHANES III). Girls (n = 956), and boys ( n = 1199), who had data on birthweight and Tanner staging were included. Maternal-reported birthweight, smoking in pregnancy and other information were provided in a home interview, while Tanner staging to assess pubertal status was part of a medical examination. Multiple logistic regression models were computed for the endpoints of the OR [95% confidence interval (CI)] of being Tanner Stage 2+ vs. 1 or being 2+ vs. 1 in an asynchronous pubertal pathway after adjustment for the complex sampling design of NHANES, age, race, height and body mass index (BMI).
Birthweight was not associated with the OR of Tanner stage 2+ among girls; however, boys who were low birthweight (<2500 g) and boys born higher than average birthweight (3500-3999 g) were more likely to be Tanner stage 2+ than 1. Childhood BMI was associated with the OR of having entered puberty among girls, but not boys. In an analysis of asynchronous maturation, girls born at high birthweight (>4000 g) were more likely to have breast development 3+ than girls of normal birthweight, OR = 3.18 [95% CI 1.39, 8.25]. Thus, the birthweight-puberty association varies by gender and by pubertal pathway. Our findings need replication in prospective longitudinal studies, and research to understand the mechanisms underlying the relation of early life exposures to cancer risk.
C1 [Olivo-Marston, Susan; Forman, Michele R.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Olivo-Marston, Susan; Forman, Michele R.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Forman, Michele R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Olivo-Marston, S (reprint author), Coll Publ Hlth, Div Epidemiol, B-215 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM solivo-marston@cph.osu.edu
FU National Cancer Institute Cancer Prevention Fellowship
FX Susan Olivo-Marston was a recipient of a National Cancer Institute
Cancer Prevention Fellowship.
NR 50
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U1 2
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAY
PY 2010
VL 24
IS 3
BP 222
EP 231
DI 10.1111/j.1365-3016.2010.01097.x
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 581DO
UT WOS:000276501800003
PM 20415751
ER
PT J
AU Pan, IJ
Daniels, JL
Herring, AH
Rogan, WJ
Siega-Riz, AM
Goldman, BD
Sjodin, A
AF Pan, I-Jen
Daniels, Julie L.
Herring, Amy H.
Rogan, Walter J.
Siega-Riz, Anna Maria
Goldman, Barbara D.
Sjodin, Andreas
TI Lactational exposure to polychlorinated biphenyls,
dichlorodiphenyltrichloroethane, and dichlorodiphenyldichloroethylene
and infant growth: an analysis of the Pregnancy, Infection, and
Nutrition Babies Study
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE breast milk contaminants; PCBs; DDT; DDE; endocrine disruptors; infant
growth
ID POLYBROMINATED DIPHENYL ETHERS; ANDROGEN RECEPTOR; PRENATAL EXPOSURE;
CHILDHOOD GROWTH; BREAST-MILK; IN-UTERO; CHILDREN; PCBS; LIFE; HEALTH
AB Polychlorinated biphenyls (PCB), 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT) and 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), the most stable metabolite of p,p'-DDT, are persistent organic pollutants and environmental endocrine disruptors. Infant exposure to these chemicals through breast feeding may influence children's growth, but this potential adverse effect could be complicated by the coexisting benefits of breast feeding. This study examined the associations between lactational exposure to these chemicals and infant growth in the first 12 months by using data from the Pregnancy, Infection and Nutrition Babies Study in central North Carolina, United States, 2004-06. The study population was restricted to the infants who were breast fed for 6 months or longer. PCBs, p,p'-DDT and p,p'-DDE were measured in breast milk at 3 months postpartum. Lactational exposure up to 12 months of age was estimated as the product of chemical concentrations and the duration of breast feeding. The infant's weight and length were recorded from the medical record for each routine paediatric well-child visit in the first 12 months. Women - child pairs who breast fed for 6 months or longer and returned the growth card (n = 210) were included in the study. Linear mixed effects models were used to assess the associations between chemical concentrations in breast milk and longitudinal infant weight and length measurements in the first 6 months. Multivariable linear regression models were used to assess the relationships between lactational exposure to chemicals until 12 months of age and the z-scores of infant weight, length and weight-for-length at 12 months.
Overall, no association was observed. Breast feeding for 6 months or longer, with lactational exposure to PCBs, p,p'-DDT and p,p'-DDE at the low background level concentrations studied here, resulted in no measurable influence on infant growth in the first 12 months.
C1 [Pan, I-Jen; Daniels, Julie L.; Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Daniels, Julie L.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Herring, Amy H.; Siega-Riz, Anna Maria] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA.
[Siega-Riz, Anna Maria] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Goldman, Barbara D.] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA.
[Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Sjodin, Andreas] Ctr Dis Control & Prevent, Organ Analyt Toxicol Branch, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA.
EM julie_daniels@unc.edu
RI Sjodin, Andreas/F-2464-2010; Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
FU National Institute of Environmental Health Sciences [P30ES10126]; U.S.
Environmental Protection Agency [RD832736]; Intramural Research Program;
National Institute of Environmental Health Sciences; National Institutes
of Health
FX This work was supported by the National Institute of Environmental
Health Sciences [grant number P30ES10126]; and the U.S. Environmental
Protection Agency [grant number RD832736]. Dr Rogan's work on this
project was supported by the Intramural Research Program, National
Institute of Environmental Health Sciences, National Institutes of
Health.
NR 43
TC 23
Z9 25
U1 2
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAY
PY 2010
VL 24
IS 3
BP 262
EP 271
DI 10.1111/j.1365-3016.2010.01114.x
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 581DO
UT WOS:000276501800008
PM 20415756
ER
PT J
AU Dworkin, RH
Turk, DC
Peirce-Sandner, S
Baron, R
Bellamy, N
Burke, LB
Chappell, A
Chartier, K
Cleeland, CS
Costello, A
Cowan, P
Dimitrova, R
Ellenberg, S
Farrar, JT
French, JA
Gilron, I
Hertz, S
Jadad, AR
Jay, GW
Kalliomaki, J
Katz, NP
Kerns, RD
Manning, DC
McDermott, MP
McGrath, PJ
Narayana, A
Porter, L
Quessy, S
Rappaport, BA
Rauschkolb, C
Reeve, BB
Rhodes, T
Sampaio, C
Simpson, DM
Stauffer, JW
Stucki, G
Tobias, J
White, RE
Witter, J
AF Dworkin, Robert H.
Turk, Dennis C.
Peirce-Sandner, Sarah
Baron, Ralf
Bellamy, Nicholas
Burke, Laurie B.
Chappell, Amy
Chartier, Kevin
Cleeland, Charles S.
Costello, Ann
Cowan, Penney
Dimitrova, Rozalina
Ellenberg, Susan
Farrar, John T.
French, Jacqueline A.
Gilron, Ian
Hertz, Sharon
Jadad, Alejandro R.
Jay, Gary W.
Kalliomaki, Jarkko
Katz, Nathaniel P.
Kerns, Robert D.
Manning, Donald C.
McDermott, Michael P.
McGrath, Patrick J.
Narayana, Arvind
Porter, Linda
Quessy, Steve
Rappaport, Bob A.
Rauschkolb, Christine
Reeve, Bryce B.
Rhodes, Thomas
Sampaio, Cristina
Simpson, David M.
Stauffer, Joseph W.
Stucki, Gerold
Tobias, Jeffrey
White, Richard E.
Witter, James
TI Research design considerations for confirmatory chronic pain clinical
trials: IMMPACT recommendations
SO PAIN
LA English
DT Review
DE Chronic pain; Randomized clinical trials; Research design; Phase 3
trials; Subject selection
ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LOW-BACK-PAIN;
MAJOR DEPRESSIVE DISORDER; OSTEOARTHRITIS-RESEARCH-SOCIETY; DIABETIC
PERIPHERAL NEUROPATHY; OXYMORPHONE EXTENDED-RELEASE; ACTIVE-CONTROL
TRIALS; CORE OUTCOME DOMAINS; LEAD-IN PERIOD
AB There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Dworkin, Robert H.; Peirce-Sandner, Sarah] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA.
[Turk, Dennis C.] Univ Washington, Seattle, WA 98195 USA.
[Baron, Ralf] Univ Kiel, Kiel, Germany.
[Bellamy, Nicholas] Univ Queensland, Brisbane, Qld, Australia.
[Burke, Laurie B.; Costello, Ann; Hertz, Sharon; Rappaport, Bob A.] US FDA, Silver Spring, MD USA.
[Chappell, Amy] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Chartier, Kevin] United BioSource Corp, Newtown, PA USA.
[Cleeland, Charles S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA.
[Dimitrova, Rozalina] Allergan Pharmaceut Inc, Irvine, CA USA.
[Ellenberg, Susan; Farrar, John T.; French, Jacqueline A.] NYU, New York, NY USA.
[Gilron, Ian] Queens Univ, Kingston, ON, Canada.
[Jadad, Alejandro R.] Univ Toronto, Toronto, ON, Canada.
[Jay, Gary W.] Schwarz Biosci, Res Triangle Pk, NC USA.
[Kalliomaki, Jarkko] AstraZeneca, Sodertalje, Sweden.
[Katz, Nathaniel P.] Analges Res, Needham, MA USA.
[Kerns, Robert D.] Dept Vet Affairs, West Haven, CT USA.
[Manning, Donald C.] Celgene Corp, Warren, NJ USA.
[McDermott, Michael P.] Univ Rochester, Rochester, NY USA.
[McGrath, Patrick J.] Dalhousie Univ, Halifax, NS, Canada.
[McGrath, Patrick J.] IWK Hlth Ctr, Halifax, NS, Canada.
[Narayana, Arvind] Cephalon Inc, Frazer, PA USA.
[Quessy, Steve] Qd Consulting LLC, Res Triangle Pk, NC USA.
[Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA.
[Reeve, Bryce B.] NCI, NIH, Bethesda, MD 20892 USA.
[Rhodes, Thomas] Merck & Co Inc, Blue Bell, PA USA.
[Sampaio, Cristina] Fac Med Lisbon, Lisbon, Portugal.
[Simpson, David M.] Mt Sinai Sch Med, New York, NY USA.
[Stauffer, Joseph W.] Alpharma, Piscataway, NJ USA.
[Stucki, Gerold] Univ Lucerne & Swiss Parapleg Res, Luzern, Switzerland.
[Tobias, Jeffrey] NeurogesX Inc, San Carlos, CA USA.
[White, Richard E.] Endo Pharmaceut Inc, Chadds Ford, PA USA.
RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA.
EM robert_dworkin@urmc.rochester.edu
RI Farrar, John/A-1037-2007; Baron, Ralf/E-4298-2010; French,
Jacqueline/G-6795-2013; Bellamy, Nicholas/G-3631-2010;
OI Farrar, John/0000-0001-8656-5157; French,
Jacqueline/0000-0003-2242-8027; McGrath, Patrick/0000-0002-9568-2571
FU US Department of Veterans Affairs; US Food and Drug Administration; US
National Institutes of Health; University of Rochester Office of
Continuing Professional Education
FX The views expressed in this article are those of the authors, none of
whom have financial conflicts of interest related to the issues
discussed in this manuscript. No official endorsement by the US
Department of Veterans Affairs, US Food and Drug Administration, US
National Institutes of Health, or the pharmaceutical companies that
provided unrestricted grants to the University of Rochester Office of
Continuing Professional Education should be inferred.; The authors thank
Paul J. Lambiase and Mary Gleichauf for their invaluable assistance in
the organization of the IMMPACT meeting and acknowledge NPK's suggestion
of the term "Good Research Practice" Unrestricted grants were provided
to the University of Rochester Office of Continuing Professional
Education to support the activities of IMMPACT, including the consensus
meeting on which this article is based, by Allergan, Alpharma,
AstraZeneca, Celgene, Cephalon, Eli Lilly, Endo, GlaxoSmithKline,
Johnson & Johnson, Merck, NeurogesX, Pfizer, and Schwarz Biosciences.
NR 158
TC 131
Z9 132
U1 4
U2 28
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD MAY
PY 2010
VL 149
IS 2
BP 177
EP 193
DI 10.1016/j.pain.2010.02.018
PG 17
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 587HK
UT WOS:000276980900007
PM 20207481
ER
PT J
AU Carol, H
Houghton, PJ
Morton, CL
Kolb, EA
Gorlick, R
Reynolds, CP
Kang, MH
Maris, JM
Keir, ST
Watkins, A
Smith, MA
Lock, RB
AF Carol, Hernan
Houghton, Peter J.
Morton, Christopher L.
Kolb, E. Anders
Gorlick, Richard
Reynolds, C. Patrick
Kang, Min H.
Maris, John M.
Keir, Stephen T.
Watkins, Amy
Smith, Malcolm A.
Lock, Richard B.
TI Initial Testing of Topotecan by the Pediatric Preclinical Testing
Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; topotecan
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; REFRACTORY ACUTE-LEUKEMIA; HIGH-RISK
NEUROBLASTOMA; CELL LUNG-CANCER; GROUP PHASE-II; TOPOISOMERASE-I;
ONCOLOGY-GROUP; SOLID TUMORS; SYSTEMIC EXPOSURE; OVARIAN-CANCER
AB Background. Topotecan is a small molecule DNA topoisomerase poison, that has been successful in clinical trials against pediatric solid tumors and leukemias. Topotecan was evaluated against the Pediatric Preclinical Testing Program (PPTP) tumor panels as part of a validation process for these preclinical models. Procedures. In vivo three measures of antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (T/C) tumor volume measure; and (3) a time to event (fourfold increase in tumor volume for solid tumor models, or >= 25% human CD45+ cells in the peripheral blood for acute lymphoblastic leukemia, ALL models) measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. Results. Topotecan inhibited cell growth in vitro with IC(50) values between 0.71 and 489 nM. Topotecan significantly increased EFS in 32 of 37 (87%) solid tumor xenografts and in all 8 of the ALL xenografts. Seventy-five percent of solid tumors met EFS TIC activity criteria for intermediate (n = 17) or high activity In = 7). Objective responses were noted in eight solid tumor xenografts (Wilms, rhabdomyosarcoma, Ewing sarcoma, neuroblastoma). Among the six neuroblastomas, three achieved a PR. For the ALL panel, two maintained CRs, three CRs, and two PRs were observed. Conclusions. Topotecan demonstrated broad activity in vitro and in vivo against both the solid tumor and ALL panels, with significant tumor growth delay generated in all the panels. These results further demonstrate the validity of the PPTP panel for preclinical testing of new drugs. Pediatr Blood Cancer 2010;54:707-715. (c) 2009 Wiley-Liss, Inc.
C1 [Carol, Hernan; Lock, Richard B.] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Houghton, Peter J.; Morton, Christopher L.; Watkins, Amy] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Lock, RB (reprint author), Childrens Canc Inst Australia, POB 81,High St, Randwick, NSW 2031, Australia.
EM rlock@ccia.unsw.edu.au
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA 108786]
FX This work was supported by NO1-CM-42216, CA21765, and CA 108786 from the
National Cancer Institute and used topotecan supplied by
GlaxoSmithKline. In addition to the authors this represents work
contributed by the following: Sherry Ansher, Catherine A. Billups,
Joshua Courtright, Edward Favours, Henry S. Friedman, Nino Keshelava,
Debbie Payne-Turner, Charles Stopford, Mayamin Tajbakhsh, Chandra
Tucker, Jianrorul Wu, Joe Zeidner, Ellen Zhang, and Jian Zhang.
Children's Cancer Institute Australia for Medical Research is affiliated
with the University of New South Wales and Sydney Children's Hospital.
NR 50
TC 27
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U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2010
VL 54
IS 5
BP 707
EP 715
DI 10.1002/pbc.22352
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 573SR
UT WOS:000275935700011
PM 20017204
ER
PT J
AU Maojo, V
Martin-Sanchez, F
Kulikowski, C
Rodriguez-Paton, A
Fritts, M
AF Maojo, Victor
Martin-Sanchez, Fernando
Kulikowski, Casimir
Rodriguez-Paton, Alfonso
Fritts, Martin
TI Nanoinformatics and DNA-Based Computing: Catalyzing Nanomedicine
SO PEDIATRIC RESEARCH
LA English
DT Review
ID SYNTHETIC BIOLOGY; CANCER; CELLS; RNA; DELIVERY; GENE; NANOPARTICLES;
INFORMATION; INTEGRATION; ONTOLOGIES
AB Five decades of research and practical application of computers in biomedicine has given rise to the discipline of medical informatics, which has made many advances in genomic and translational medicine possible. Developments in nanotechnology are opening up the prospects for nanomedicine and regenerative medicine where informatics and DNA computing can become the catalysts enabling health care applications at sub-molecular or atomic scales. Although nanomedicine promises a new exciting frontier for clinical practice and biomedical research, issues involving cost-effectiveness studies, clinical trials and toxicity assays, drug delivery methods, and the implementation of new personalized therapies still remain challenging. Nanoinformatics can accelerate the introduction of nano-related research and applications into clinical practice, leading to an area that could be called "translational nanoinformatics." At the same time, DNA and RNA computing presents an entirely novel paradigm for computation. Nanoinformatics and DNA-based computing are together likely to completely change the way we model and process information in biomedicine and impact the emerging field of nanomedicine most strongly. In this article, we review work in nanoinformatics and DNA (and RNA)-based computing, including applications in nanopediatrics. We analyze their scientific foundations, current research and projects, envisioned applications and potential problems that might arise from them. (Pediatr Res 67: 481-489, 2010)
C1 [Maojo, Victor; Rodriguez-Paton, Alfonso] Univ Politecn Madrid, Dept Inteligencia Artificial, E-28660 Madrid, Spain.
[Martin-Sanchez, Fernando] Natl Inst Hlth Carlos III, Med Bioinformat Dept, Madrid 28220, Spain.
[Kulikowski, Casimir] Rutgers State Univ, Dept Comp Sci, Piscataway, NJ 08855 USA.
[Fritts, Martin] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Maojo, V (reprint author), Univ Politecn Madrid, Dept Inteligencia Artificial, E-28660 Madrid, Spain.
EM vmaojo@fi.upm.es
RI Rodriguez-Paton, Alfonso/H-1003-2011
OI Rodriguez-Paton, Alfonso/0000-0001-7289-2114
FU European Commission; Ministry of Science and Innovation of Spain;
Comunidad de Madrid
FX Supported, in part, by the European Commission (Action-Grid project),
the Ministry of Science and Innovation of Spain (COMBIOMED RETICS, FIS
and the ONTOMINEBASE project), and the Comunidad de Madrid.
NR 59
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U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD MAY
PY 2010
VL 67
IS 5
BP 481
EP 489
PG 9
WC Pediatrics
SC Pediatrics
GA 587DJ
UT WOS:000276968000005
PM 20118825
ER
PT J
AU Schneeweiss, S
Patrick, AR
Solomon, DH
Dormuth, CR
Miller, M
Mehta, J
Lee, JC
Wang, PS
AF Schneeweiss, Sebastian
Patrick, Amanda R.
Solomon, Daniel H.
Dormuth, Colin R.
Miller, Matt
Mehta, Jyotsna
Lee, Jennifer C.
Wang, Philip S.
TI Comparative Safety of Antidepressant Agents for Children and Adolescents
Regarding Suicidal Acts
SO PEDIATRICS
LA English
DT Article
DE antidepressant medications; fluoxetine; suicide; intentional self-harm;
cohort study; epidemiology
ID PROPENSITY SCORE; SELF-HARM; RISK; METAANALYSIS; DEPRESSION; STRATEGIES;
TRIALS; COHORT; DRUGS
AB OBJECTIVE: The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents.
METHODS: We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antide-pressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death.
RESULTS: Of 20 906 children who initiated antidepressant therapy, 16 774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9-30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54-1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46-2.43]), paroxetine (RR: 0.80 [95% CI: 0.47-1.37]), and sertraline (RR: 1.02 [95% CI: 0.56-1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43-2.00]).
CONCLUSION: Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants. Pediatrics 2010;125:876-888
C1 [Schneeweiss, Sebastian; Patrick, Amanda R.; Solomon, Daniel H.; Mehta, Jyotsna; Lee, Jennifer C.; Wang, Philip S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02120 USA.
[Miller, Matt] Harvard Univ, Harvard Injury Control Res Ctr, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02120 USA.
[Dormuth, Colin R.] Univ British Columbia, Therapeut Initiat, Dept Anesthesia Pharmacol & Therapeut, Vancouver, BC V5Z 1M9, Canada.
[Wang, Philip S.] NIMH, Off Director, Bethesda, MD 20892 USA.
RP Schneeweiss, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
EM schneeweiss@post.harvard.edu
RI miller, matthew/H-4624-2011; Schneeweiss, Sebastian/C-2125-2013;
OI miller, matthew/0000-0002-3267-6510; Dormuth, Colin/0000-0001-8577-8783
FU National Institute of Mental Health [R01-MH078708]
FX This project was funded by a grant from the National Institute of Mental
Health ( grant R01-MH078708).
NR 31
TC 39
Z9 40
U1 1
U2 5
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 MAY
PY 2010
VL 125
IS 5
BP 876
EP 888
DI 10.1542/peds.2009-2317
PG 13
WC Pediatrics
SC Pediatrics
GA 590NI
UT WOS:000277232800003
PM 20385637
ER
PT J
AU Anand, KJS
Willson, DF
Berger, J
Harrison, R
Meert, KL
Zimmerman, J
Carcillo, J
Newth, CJL
Prodhan, P
Dean, JM
Nicholson, C
AF Anand, Kanwaljeet J. S.
Willson, Douglas F.
Berger, John
Harrison, Rick
Meert, Kathleen L.
Zimmerman, Jerry
Carcillo, Joseph
Newth, Christopher J. L.
Prodhan, Parthak
Dean, J. Michael
Nicholson, Carol
CA Eunice Kennedy Shriver Natl Inst H
TI Tolerance and Withdrawal From Prolonged Opioid Use in Critically III
Children
SO PEDIATRICS
LA English
DT Review
DE tolerance; withdrawal; abstinence; opiate; opioid; narcotic; stress;
critical illness
ID PEDIATRIC INTENSIVE-CARE; POPULATION CLINICAL-PHARMACOLOGY; SINGLE
NUCLEOTIDE POLYMORPHISMS; CATECHOL-O-METHYLTRANSFERASE;
NARCOTIC-ABSTINENCE SYNDROME; SEDATIVES AND/OR ANALGESICS; OXIDE
SYNTHASE INHIBITORS; CHRONIC MORPHINE EXPOSURE; SIGNAL-REGULATED KINASE;
LOW GESTATIONAL-AGE
AB OBJECTIVE: After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal.
PATIENTS AND METHODS: Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis.
RESULTS: Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia.
CONCLUSIONS: Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal. Pediatrics 2010; 125: e1208-e1225
C1 [Anand, Kanwaljeet J. S.] Le Bonheur Childrens Hosp, Dept Pediat, Memphis, TN USA.
[Anand, Kanwaljeet J. S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Willson, Douglas F.] Univ Virginia, Childrens Hosp, Dept Pediat & Anesthesiol, Charlottesville, VA USA.
[Berger, John] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Zimmerman, Jerry] Childrens Hosp & Med Ctr, Dept Pediat, Seattle, WA 98105 USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA.
[Prodhan, Parthak] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Dean, J. Michael] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Nicholson, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Crit Care & Rehabil Program, NCMRR, NIH, Bethesda, MD USA.
RP Anand, KJS (reprint author), Lebonheur Childrens Hosp & Med Ctr, Room 4624,50 N Dunlap St, Memphis, TN 38103 USA.
EM anandsunny@uams.edu
RI Benneyworth, Brian/A-4667-2009;
OI Benneyworth, Brian/0000-0002-4692-5303; Anand,
Kanwaljeet/0000-0001-6498-1483
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development [U10HD050096,
U10HD049981, U10HD500009, U10HD049945, U10HD049983, U10HD050012,
U01HD049934]
FX Funded by the National Institutes of Health (NIH).; This work was
supported by Eunice Kennedy Shriver National Institute of Child Health
and Human Development cooperative agreements U10HD050096, U10HD049981,
U10HD500009, U10HD049945, U10HD049983, U10HD050012, and U01HD049934. We
thank Pam Cate and Kris Dudoich for administrative assistance.
NR 260
TC 70
Z9 73
U1 2
U2 16
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 MAY
PY 2010
VL 125
IS 5
BP E1208
EP E1225
DI 10.1542/peds.2009-0489
PG 18
WC Pediatrics
SC Pediatrics
GA 590NI
UT WOS:000277232800057
PM 20403936
ER
PT J
AU Norman, SA
Weber, AL
Localio, AR
Marchbanks, PA
Ursin, G
Strom, BL
Weiss, LK
Burkman, RT
Bernstein, L
Deapen, DM
Folger, SG
Simon, MS
Nadel, MR
AF Norman, Sandra A.
Weber, Anita L.
Localio, A. Russell
Marchbanks, Polly A.
Ursin, Giske
Strom, Brian L.
Weiss, Linda K.
Burkman, Ronald T.
Bernstein, Leslie
Deapen, Dennis M.
Folger, Suzanne G.
Simon, Michael S.
Nadel, Marion R.
TI Hormone therapy and fatal breast cancer
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE hormone replacement therapy; estrogen replacement therapy; estrogen
progestin combination therapy; breast neoplasms; death; menopause;
case-control
ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; INITIATIVE
RANDOMIZED-TRIAL; REPLACEMENT THERAPY; PROGNOSTIC-FACTORS; RISK;
MAMMOGRAPHY; MORTALITY; REGIMENS; POPULATION
AB Purpose Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use.
Methods HT use prior to breast cancer diagnosis in 278 women who died of breast cancer within 6 years of diagnosis (cases) was compared with use in 2224 controls never diagnosed with breast cancer using conditional logistic regression. Measures taken to address potential bias and confounding inherent in case-control studies included collecting and adjusting for detailed data on demographic and other factors potentially associated both with HT use and breast cancer.
Results Fifty-six per cent of cases and 68% of controls reported HT use. Among current 3+ year HT users, odds ratios and 95% confidence intervals for death were 0.83 (0.50, 1.38) and 0.69 (0.44, 1.09), respectively, for exclusive use of CHT or of ET, and were 0.94 (0.59, 1.48) and 0.70 (0.45, 1.07) for any use of CHT or of ET regardless of other hormone use.
Conclusion Point estimates suggest no increased risk of fatal breast cancer with HT use, although 50% increases in risk in longer-term current CHT users cannot be ruled out. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Norman, Sandra A.; Weber, Anita L.; Localio, A. Russell; Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Norman, Sandra A.; Localio, A. Russell; Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Marchbanks, Polly A.; Folger, Suzanne G.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA.
[Ursin, Giske; Bernstein, Leslie; Deapen, Dennis M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Ursin, Giske] Univ Oslo, Dept Nutr, N-0316 Oslo, Norway.
[Weiss, Linda K.] NCI, Canc Ctr Branch, Bethesda, MD 20892 USA.
[Burkman, Ronald T.] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA.
[Simon, Michael S.] Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA.
[Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA.
[Nadel, Marion R.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Norman, SA (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, 8 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM snorman@mail.med.upenn.edu
FU Centers for Disease Control and Prevention (CDC); Division of Cancer
Prevention and Control [200-2002-00370]; National Institute of Child
Health and Human Development (NICHD); NICHD; National Cancer Institute
[N01-HD-3-3168]; Fred Hutchinson Cancer Research Center [N01-HD-2-3166];
Karmanos Cancer Institute at Wayne State University [N01-HD-3-3174];
University of Pennsylvania [N01-HD-3-3176]; University of Southern
California [N01-HD-3-3175]; CDC [Y01-HD-7022]; Surveillance,
Epidemiology and End Results Program [N01-PC-67006, N01-CN-65064,
N01-PC-67010, N01-CN-0532]
FX This study was funded by the Centers for Disease Control and Prevention
(CDC), Division of Cancer Prevention and Control, through subcontracts
to the Women's Contraceptive and Reproductive Experiences (CARE) Study
through an interagency agreement with the National Institute of Child
Health and Human Development (NICHD), and by CDC Division of Cancer
Prevention and Control contract #200-2002-00370 with the University of
Pennsylvania (Sandra A. Norman, P.I.). The Women's CARE Study was funded
by the NICHD, with additional support from the National Cancer
Institute, through contracts with Emory University (N01-HD-3-3168), Fred
Hutchinson Cancer Research Center (N01-HD-2-3166), Karmanos Cancer
Institute at Wayne State University (N01-HD-3-3174), the University of
Pennsylvania (N01-HD-3-3176), and the University of Southern California
(N01-HD-3-3175) and through an interagency agreement with CDC
(Y01-HD-7022). CDC also contributed additional staff and computer
support. General support was also provided through Surveillance,
Epidemiology and End Results Program contracts N01-PC-67006 (Atlanta),
N01-CN-65064 (Detroit), N01-PC-67010 (Los Angeles), and N01-CN-0532
(Seattle). The authors thank Noel S. Weiss, MD, DrPH for his many
helpful suggestions on drafts of the paper.
NR 43
TC 9
Z9 9
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD MAY
PY 2010
VL 19
IS 5
BP 440
EP 447
DI 10.1002/pds.1941
PG 8
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 600LM
UT WOS:000277987600003
PM 20336635
ER
PT J
AU Goto, K
Chiba, Y
Matsusue, K
Hattori, Y
Maitani, Y
Sakai, H
Kimura, S
Misawa, M
AF Goto, Kumiko
Chiba, Yoshihiko
Matsusue, Kimihiko
Hattori, Yoshiyuki
Maitani, Yoshie
Sakai, Hiroyasu
Kimura, Shioko
Misawa, Miwa
TI The proximal STAT6 and NF-kappa B sites are responsible for IL-13-and
TNF-alpha-induced RhoA transcriptions in human bronchial smooth muscle
cells
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE RhoA; STAT6; NF-kappa B; Airway hyperresponsiveness; IL-13; TNF-alpha
ID NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-C; CORONARY-ARTERY SPASM; MYOSIN
LIGHT-CHAIN; AIRWAY HYPERRESPONSIVENESS; CA2+ SENSITIZATION; CALCIUM
SENSITIZATION; EPITHELIAL-CELLS; ASTHMA; INTERLEUKIN-13
AB RhoA protein is involved in the Ca(2+) sensitization of bronchial smooth muscle (BSM) contraction, and an upregulation of RhoA in BSMs has been suggested in allergic bronchial asthma. However, the mechanism of upregulation of RhoA remains poorly understood. In the present study, the transcriptional regulation of human RhoA gene was investigated in cultured human BSM cells stimulated with IL-13 and TNF-alpha, both of which have an ability to upregulate RhoA protein. Luciferase-based assay showed that the RhoA promoter activity was augmented by both IL-13 and TNF-alpha. The deletion studies revealed a significant level of promoter activity between the 112 bp upstream and the transcription start site, which contains the STAT6 (78-70 bp upstream) and NF-kappa B (84-74 bp upstream) binding regions. The promoter activity was also decreased significantly by the mutations of these regions. Thus, the current study for the first time characterized the transcriptional regulation of the human RhoA gene. The findings also suggest that STAT6 and NF-kappa B are important for the upregulation of RhoA in human BSM induced by IL-13 and TNF-alpha, both of which are major cytokines in the pathogenesis of allergic bronchial asthma. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Goto, Kumiko; Chiba, Yoshihiko; Sakai, Hiroyasu; Misawa, Miwa] Hoshi Univ, Sch Pharm, Dept Pharmacol, Shinagawa Ku, Tokyo 1428501, Japan.
[Matsusue, Kimihiko] Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan.
[Hattori, Yoshiyuki; Maitani, Yoshie] Hoshi Univ, Sch Pharm, Dept Inst Med Chem, Shinagawa Ku, Tokyo 142850, Japan.
[Matsusue, Kimihiko; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Chiba, Y (reprint author), Hoshi Univ, Sch Pharm, Dept Pharmacol, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan.
EM chiba@hoshi.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
FX The authors thank Taiki Kobayashi and Makiko Momata for their technical
assistance. This work was partly supported by the Ministry of Education,
Culture, Sports, Science and Technology of Japan.
NR 46
TC 12
Z9 13
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD MAY
PY 2010
VL 61
IS 5
BP 466
EP 472
DI 10.1016/j.phrs.2009.12.001
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 584RG
UT WOS:000276769600013
PM 20006706
ER
PT J
AU Souza, JA
Neumeier, JJ
White, BD
Yu, YK
AF Souza, J. A.
Neumeier, J. J.
White, B. D.
Yu, Yi-Kou
TI Analysis of the critical behavior associated with the antiferromagnetic
transitions of LaMnO3 and CaMnO3
SO PHYSICAL REVIEW B
LA English
DT Article
ID HEAT-CAPACITY; THERMODYNAMIC PROPERTIES; CURIE-TEMPERATURE; EXCHANGE;
RBMNF3; SYSTEM
AB We apply a method for analyzing phase transitions to the well-known antiferromagnets LaMnO3 and CaMnO3 using high-resolution thermal-expansion data. The critical exponents associated with the specific heat (alpha) are obtained. Within experimental error, the results suggest that LaMnO3 and CaMnO3 belong to the same universality class. An additional byproduct of our analysis is estimates for the pressure derivative of the magnetic phase transition temperature.
C1 [Souza, J. A.; Neumeier, J. J.; White, B. D.] Montana State Univ, Dept Phys, Bozeman, MT 59717 USA.
[Souza, J. A.] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09090400 Santo Andre, SP, Brazil.
[Yu, Yi-Kou] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Souza, JA (reprint author), Montana State Univ, Dept Phys, POB 173840, Bozeman, MT 59717 USA.
EM joseantonio.souza@ufabc.edu.br
RI Souza, Jose/G-5555-2012
OI Souza, Jose/0000-0002-6832-3581
FU CNPq [201017/2005-9, 471863/2008-4, 307436/2008-0]; National Science
Foundation [DMR-0504769]; U.S. Department of Energy, Office of Basic
Energy Sciences [DE-FG06ER46269]; NIH
FX This material is based upon work supported by the Brazilian agency CNPq
(Grants No. 201017/2005-9, No. 471863/2008-4, and No. 307436/2008-0),
National Science Foundation (Grant No. DMR-0504769), U.S. Department of
Energy, Office of Basic Energy Sciences (Grant No. DE-FG06ER46269) and
the Intramural Research Program of the National Library of Medicine at
the NIH.
NR 29
TC 9
Z9 9
U1 0
U2 22
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1098-0121
J9 PHYS REV B
JI Phys. Rev. B
PD MAY 1
PY 2010
VL 81
IS 17
AR 172410
DI 10.1103/PhysRevB.81.172410
PG 4
WC Physics, Condensed Matter
SC Physics
GA 602LV
UT WOS:000278141600018
ER
PT J
AU Dean, DS
Horgan, RR
Naji, A
Podgornik, R
AF Dean, David S.
Horgan, Ron R.
Naji, Ali
Podgornik, Rudolf
TI Effects of dielectric disorder on van der Waals interactions in slab
geometries
SO PHYSICAL REVIEW E
LA English
DT Article
ID FORCES
AB We analyze the effects of disorder on the thermal Casimir interaction for the case of two semi-infinite planar slabs across an intervening homogeneous unstructured dielectric. The semi-infinite bounding layers are assumed to be composed of plane-parallel layers of random dielectric materials. We show that the effective thermal Casimir interaction at long distances is self-averaging and can be written in the same form as the one between nonrandom media but with the effective dielectric tensor of the corresponding random media. On the contrary, the behavior at short distances becomes random, and thus sample dependent, dominated by the local values of the dielectric constants proximal to each other across the central homogeneous unstructured dielectric layer. We extend these results to the regime of intermediate slab separations by using perturbation theory for weak disorder as well as by extensive numerical simulations for a number of systems where the dielectric function has a log-normal distribution. Numerical simulation completely corroborates all the main features of the disorder dependent thermal Casimir interaction deduced analytically.
C1 [Dean, David S.; Horgan, Ron R.; Naji, Ali; Podgornik, Rudolf] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
[Dean, David S.] Univ Toulouse 3, Phys Theor Lab, IRSAMC, F-31062 Toulouse 4, France.
[Horgan, Ron R.] Univ Cambridge, CMS, DAMTP, Cambridge CB3 0WA, England.
[Naji, Ali] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
[Naji, Ali] Univ Calif Santa Barbara, Dept Phys, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
[Naji, Ali] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA.
[Naji, Ali] Inst Res Fundamental Sci IPM, Sch Phys, Tehran 19395553, Iran.
[Podgornik, Rudolf] Univ Ljubljana, Dept Phys, Fac Math & Phys, SI-1000 Ljubljana, Slovenia.
[Podgornik, Rudolf] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia.
[Podgornik, Rudolf] NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA.
RP Dean, DS (reprint author), Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
RI Naji, Ali/F-6352-2010; Podgornik, Rudolf/C-6209-2008; Dean,
David/N-6601-2013
OI Naji, Ali/0000-0003-3436-1499; Podgornik, Rudolf/0000-0002-3855-4637;
FU National Science Foundation [PHY05-51164]; Institut Universtaire de
France; Agency for Research and Development of Slovenia [P1-0055C,
Z1-7171, L2-7080]; NIH, Eunice Kennedy Shriver National Institute of
Child Health and Human Development; Royal Society; Royal Academy of
Engineering; British Academy (UK)
FX This research was supported in part by the National Science Foundation
under Grant No. PHY05-51164 (while at the KITP program The theory and
practice of fluctuation induced interactions). D.S.D. acknowledges
support from the Institut Universtaire de France. R.P. would like to
acknowledge the financial support by the Agency for Research and
Development of Slovenia, Grants No. P1-0055C, No. Z1-7171, and No.
L2-7080. This study was supported in part by the Intramural Research
Program of the NIH, Eunice Kennedy Shriver National Institute of Child
Health and Human Development. A.N. thanks the Royal Society, the Royal
Academy of Engineering, and the British Academy (UK).
NR 21
TC 12
Z9 12
U1 4
U2 14
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD MAY
PY 2010
VL 81
IS 5
AR 051117
DI 10.1103/PhysRevE.81.051117
PN 1
PG 13
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 602OJ
UT WOS:000278148400027
PM 20866195
ER
PT J
AU Drennan, KJ
Linnemann, AK
Platts, AE
Heng, HH
Armant, DR
Krawetz, SA
AF Drennan, K. J.
Linnemann, A. K.
Platts, A. E.
Heng, H. H.
Armant, D. R.
Krawetz, S. A.
TI Nuclear Matrix Association: Switching to the Invasive Cytotrophoblast
SO PLACENTA
LA English
DT Article
DE Epigenetics; Trophoblast; Invasion; Nuclear matrix; Gene expression
ID SPIRAL ARTERY TRANSFORMATION; REAL-TIME PCR; GENE-EXPRESSION; HUMAN
TROPHOBLAST; ATTACHMENT-REGIONS; NORMAL-PREGNANCY; IN-SILICO; HLA-G;
DIFFERENTIATION; GROWTH
AB Abnormal trophoblast invasion is associated with the most common and most severe complications of human pregnancy. The biology of invasion, as well as the etiology of abnormal invasion remains poorly understood. The aim of this study was to characterize the transcriptome of the HTR-8/SVneo human cytotrophoblast cell line which displays well characterized invasive and non-invasive behavior, and to correlate the activity of the transcriptome with nuclear matrix attachment and cell phenotype. Comparison of the invasive to non-invasive HTR transcriptomes was unremarkable. In contrast, comparison of the MARS on chromosomes 14-18 revealed an increased number of MARs associated with the invasive phenotype. These attachment areas were more likely to be associated with silent rather than actively transcribed genes. This study supports the view that nuclear matrix attachment may play an important role in cytotrophoblast invasion by ensuring specific silencing that facilitates invasion. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Krawetz, S. A.] Wayne State Univ, Dept Obstet & Gynecol, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Armant, D. R.] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
[Krawetz, S. A.] Wayne State Univ, Inst Comp Sci, Detroit, MI 48201 USA.
RP Krawetz, SA (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Ctr Mol Med & Genet, 253 CS Mott Ctr,275 E Hancock St, Detroit, MI 48201 USA.
EM steve@compbio.med.wayne.edu
RI Platts, Adrian/H-5633-2013;
OI Platts, Adrian/0000-0001-9238-9647; Armant, D.
Randall/0000-0001-5904-9325
FU Wayne State University department of Obstetrics and Gynecology; NICHD,
NIH
FX The authors would like to thank the Wayne State University department of
Obstetrics and Gynecology for funding this research through a fellow-in
training grant to KJD. Additionally we would like to thank Brian
Kilburn, Claudia Lalancette, Graham Johnson, and Robert Goodrich for
technical support for this project as well as Ed Sendler for lending his
analytical expertise to this project. This research was supported in
part by the Intramural Research Program of the NICHD, NIH. The authors
would also like to thank Dr. Charles Graham of Queens University,
Kingston, Ontario, for providing the HTR-8/SVneo cell line.
NR 46
TC 4
Z9 4
U1 0
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD MAY
PY 2010
VL 31
IS 5
BP 365
EP 372
DI 10.1016/j.placenta.2010.02.012
PG 8
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 604MN
UT WOS:000278283200003
PM 20346505
ER
PT J
AU Canham, MA
Sharov, AA
Ko, MSH
Brickman, JM
AF Canham, Maurice A.
Sharov, Alexei A.
Ko, Minoru S. H.
Brickman, Joshua M.
TI Functional Heterogeneity of Embryonic Stem Cells Revealed through
Translational Amplification of an Early Endodermal Transcript
SO PLOS BIOLOGY
LA English
DT Article
ID ANTERIOR VISCERAL ENDODERM; MOUSE EMBRYO; SELF-RENEWAL; ES CELLS;
PRIMITIVE ENDODERM; OLIGONUCLEOTIDE MICROARRAY; NODAL ANTAGONISTS;
REPORTER SYSTEM; GENE-EXPRESSION; GATA FACTORS
AB ES cells are defined as self-renewing, pluripotent cell lines derived from early embryos. Cultures of ES cells are also characterized by the expression of certain markers thought to represent the pluripotent state. However, despite the widespread expression of key markers such as Oct4 and the appearance of a characteristic undifferentiated morphology, functional ES cells may represent only a small fraction of the cultures grown under self-renewing conditions. Thus phenotypically "undifferentiated'' cells may consist of a heterogeneous population of functionally distinct cell types. Here we use a transgenic allele designed to detect low level transcription in the primitive endoderm lineage as a tool to identify an immediate early endoderm-like ES cell state. This reporter employs a tandem array of internal ribosomal entry sites to drive translation of an enhanced Yellow Fluorescent Protein (Venus) from the transcript that normally encodes for the early endodermal marker Hex. Expression of this Venus transgene reports on single cells with low Hex transcript levels and reveals the existence of distinct populations of Oct4 positive undifferentiated ES cells. One of these cells types, characterized by both the expression of the Venus transgene and the ES cells marker SSEA-1 (V(+)S(+)), appears to represent an early step in primitive endoderm specification. We show that the fraction of cells present within this state is influenced by factors that both promote and suppress primitive endoderm differentiation, but conditions that support ES cell self-renewal prevent their progression into differentiation and support an equilibrium between this state and at least one other that resembles the Nanog positive inner cell mass of the mammalian blastocysts. Interestingly, while these subpopulations are equivalently and clonally interconvertible under self-renewing conditions, when induced to differentiate both in vivo and in vitro they exhibit different behaviours. Most strikingly when introduced back into morulae or blastocysts, the V(+)S(+) population is not effective at contributing to the epiblast and can contribute to the extra-embryonic visceral and parietal endoderm, while the V(-)S(+) population generates high contribution chimeras. Taken together our data support a model in which ES cell culture has trapped a set of interconvertible cell states reminiscent of the early stages in blastocyst differentiation that may exist only transiently in the early embryo.
C1 [Canham, Maurice A.; Brickman, Joshua M.] Univ Edinburgh, Sch Biol Sci, MRC, Inst Stem Cell Res,Ctr Regenerat Med, Edinburgh, Midlothian, Scotland.
[Sharov, Alexei A.; Ko, Minoru S. H.] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Canham, MA (reprint author), Univ Edinburgh, HPV Res Grp, Div Pathol, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland.
EM Josh.Brickman@ed.ac.uk
RI Ko, Minoru/B-7969-2009;
OI Ko, Minoru/0000-0002-3530-3015; Brickman, Joshua/0000-0003-1580-7491
FU Medical Research Council (MRC) [G0701428]; Scottish Funding Council;
National Institutes of Health (NIH), National Institute on Aging [Z01AG
AG000656, Z01AG000662]
FX This research was supported by the Medical Research Council (MRC)
(G0701428), Scottish Funding Council and, in part, by the Intramural
Research Program of the National Institutes of Health (NIH), National
Institute on Aging (Z01AG AG000656, Z01AG000662). JMB is supported by an
MRC Senior Non-Clinical Fellowship. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 63
TC 120
Z9 121
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD MAY
PY 2010
VL 8
IS 5
AR e1000379
DI 10.1371/journal.pbio.1000379
PG 16
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 610TI
UT WOS:000278759600014
PM 20520791
ER
PT J
AU Demarre, G
Chattoraj, DK
AF Demarre, Gaelle
Chattoraj, Dhruba K.
TI DNA Adenine Methylation Is Required to Replicate Both Vibrio cholerae
Chromosomes Once per Cell Cycle
SO PLOS GENETICS
LA English
DT Article
ID ESCHERICHIA-COLI CHROMOSOME; DAM METHYLTRANSFERASE; SEQA PROTEIN;
GENE-REGULATION; INITIATION; PLASMID; DIVISION; SEQUENCE; INACTIVATION;
SEGREGATION
AB DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication.
C1 [Demarre, Gaelle; Chattoraj, Dhruba K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Demarre, G (reprint author), CNRS, Ctr Genet Mol, UPR 2167, Gif Sur Yvette, France.
EM chattoraj@nih.gov
FU Center for Cancer Research, National Cancer Institute
FX This work was supported by the Intramural Research Program, Center for
Cancer Research, the National Cancer Institute. The funder had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 59
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2010
VL 6
IS 5
AR e1000939
DI 10.1371/journal.pgen.1000939
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 608BU
UT WOS:000278557300009
PM 20463886
ER
PT J
AU Gibbs, JR
van der Brug, MP
Hernandez, DG
Traynor, BJ
Nalls, MA
Lai, SL
Arepalli, S
Dillman, A
Rafferty, IP
Troncoso, J
Johnson, R
Zielke, HR
Ferrucci, L
Longo, DL
Cookson, MR
Singleton, AB
AF Gibbs, J. Raphael
van der Brug, Marcel P.
Hernandez, Dena G.
Traynor, Bryan J.
Nalls, Michael A.
Lai, Shiao-Lin
Arepalli, Sampath
Dillman, Allissa
Rafferty, Ian P.
Troncoso, Juan
Johnson, Robert
Zielke, H. Ronald
Ferrucci, Luigi
Longo, Dan L.
Cookson, Mark R.
Singleton, Andrew B.
TI Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene
Expression in Human Brain
SO PLOS GENETICS
LA English
DT Article
ID MICROARRAY DATA; GENOME; HAPLOTYPE; PATTERNS; OMNIBUS; DISEASE
AB A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total). We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation.
C1 [Gibbs, J. Raphael; van der Brug, Marcel P.; Hernandez, Dena G.; Traynor, Bryan J.; Nalls, Michael A.; Lai, Shiao-Lin; Arepalli, Sampath; Dillman, Allissa; Rafferty, Ian P.; Cookson, Mark R.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Gibbs, J. Raphael; Hernandez, Dena G.; Lai, Shiao-Lin] UCL, Dept Mol Neurosci, Inst Neurol, London, England.
[Gibbs, J. Raphael; Hernandez, Dena G.; Lai, Shiao-Lin] UCL, Inst Neurol, Reta Lila Weston Labs, London, England.
[van der Brug, Marcel P.] Scripps Res Inst, Dept Mol & Integrat Neurosci, Jupiter, FL USA.
[Troncoso, Juan] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
[Johnson, Robert; Zielke, H. Ronald] Univ Maryland, Sch Med, NICHHD, Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA.
RP Gibbs, JR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov; singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [Z01 AG000949-02, Z01 AG000015-49]
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, Department
of Health and Human Services, and relates to Intramural program numbers
Z01 AG000949-02 and Z01 AG000015-49. Methylation assays were received at
no cost from Illumina as a part of an early access agreement. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
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U1 1
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2010
VL 6
IS 5
AR e1000952
DI 10.1371/journal.pgen.1000952
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 608BU
UT WOS:000278557300022
PM 20485568
ER
PT J
AU Wang, ZL
Rhee, DB
Lu, JA
Bohr, CT
Zhou, F
Vallabhaneni, H
de Souza-Pinto, NC
Liu, Y
AF Wang, Zhilong
Rhee, David B.
Lu, Jian
Bohr, Christina T.
Zhou, Fang
Vallabhaneni, Haritha
de Souza-Pinto, Nadja C.
Liu, Yie
TI Characterization of Oxidative Guanine Damage and Repair in Mammalian
Telomeres
SO PLOS GENETICS
LA English
DT Article
ID BASE EXCISION-REPAIR; ONE-ELECTRON OXIDATION; DNA-DAMAGE;
SACCHAROMYCES-CEREVISIAE; DYSFUNCTIONAL TELOMERES; HOMOLOGOUS
RECOMBINATION; NUCLEIC-ACIDS; GGG TRIPLETS; STRAND BREAK; CELL-DEATH
AB 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1)-initiated DNA base excision repair (BER). Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere-FISH), by chromosome orientation-FISH (CO-FISH), and by indirect immunofluorescence in combination with telomere-FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1(-/-)) mouse tissues and primary embryonic fibroblasts (MEFs) cultivated in hypoxia condition (3% oxygen), whereas telomere shortening was detected in Ogg1(-/-) mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen) or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1(-/-) mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1(-/-) mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1(-/-) MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity in mammals.
C1 [Wang, Zhilong; Rhee, David B.; Lu, Jian; Bohr, Christina T.; Zhou, Fang; Vallabhaneni, Haritha; de Souza-Pinto, Nadja C.; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Rhee, David B.] Univ Tennessee, Oak Ridge Natl Lab, Grad Sch Genome Sci & Technol, Knoxville, TN USA.
RP Wang, ZL (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM liuyie@mail.nih.gov
RI Lu, Jian/G-8391-2011; Souza-Pinto, Nadja/C-3462-2013; 3,
INCT/H-4497-2013; Redoxoma, Inct/H-9962-2013
OI Lu, Jian/0000-0001-6522-8485; Souza-Pinto, Nadja/0000-0003-4206-964X;
FU NIA, National Institutes of Health; UT-ORNL Graduate School of Genome
Science and Technology
FX This work was supported by funds from the Intramural Research Program of
the NIA, National Institutes of Health. DBR was supported by UT-ORNL
Graduate School of Genome Science and Technology. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 68
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U1 0
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2010
VL 6
IS 5
AR e1000951
DI 10.1371/journal.pgen.1000951
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 608BU
UT WOS:000278557300021
PM 20485567
ER
PT J
AU Ambs, S
AF Ambs, Stefan
TI Prognostic Significance of Subtype Classification for Short- and
Long-Term Survival in Breast Cancer: Survival Time Holds the Key
SO PLOS MEDICINE
LA English
DT Editorial Material
ID ESTROGEN-RECEPTOR STATUS; EXPRESSION; CHEMOTHERAPY; TUMORS
C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
NR 16
TC 5
Z9 5
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD MAY
PY 2010
VL 7
IS 5
AR e1000281
DI 10.1371/journal.pmed.1000281
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608CV
UT WOS:000278560500014
PM 20520798
ER
PT J
AU Blows, FM
Driver, KE
Schmidt, MK
Broeks, A
van Leeuwen, FE
Wesseling, J
Cheang, MC
Gelmon, K
Nielsen, TO
Blomqvist, C
Heikkila, P
Heikkinen, T
Nevanlinna, H
Akslen, LA
Begin, LR
Foulkes, WD
Couch, FJ
Wang, X
Cafourek, V
Olson, JE
Baglietto, L
Giles, GG
Severi, G
McLean, CA
Southey, MC
Rakha, E
Green, AR
Ellis, IO
Sherman, ME
Lissowska, J
Anderson, WF
Cox, A
Cross, SS
Reed, MWR
Provenzano, E
Dawson, SJ
Dunning, AM
Humphreys, M
Easton, DF
Garcia-Closas, M
Caldas, C
Pharoah, PD
Huntsman, D
AF Blows, Fiona M.
Driver, Kristy E.
Schmidt, Marjanka K.
Broeks, Annegien
van Leeuwen, Flora E.
Wesseling, Jelle
Cheang, Maggie C.
Gelmon, Karen
Nielsen, Torsten O.
Blomqvist, Carl
Heikkila, Paivi
Heikkinen, Tuomas
Nevanlinna, Heli
Akslen, Lars A.
Begin, Louis R.
Foulkes, William D.
Couch, Fergus J.
Wang, Xianshu
Cafourek, Vicky
Olson, Janet E.
Baglietto, Laura
Giles, Graham G.
Severi, Gianluca
McLean, Catriona A.
Southey, Melissa C.
Rakha, Emad
Green, Andrew R.
Ellis, Ian O.
Sherman, Mark E.
Lissowska, Jolanta
Anderson, William F.
Cox, Angela
Cross, Simon S.
Reed, Malcolm W. R.
Provenzano, Elena
Dawson, Sarah-Jane
Dunning, Alison M.
Humphreys, Manjeet
Easton, Douglas F.
Garcia-Closas, Montserrat
Caldas, Carlos
Pharoah, Paul D.
Huntsman, David
TI Subtyping of Breast Cancer by Immunohistochemistry to Investigate a
Relationship between Subtype and Short and Long Term Survival: A
Collaborative Analysis of Data for 10,159 Cases from 12 Studies
SO PLOS MEDICINE
LA English
DT Article
ID TUMOR CHARACTERISTICS; PREMENOPAUSAL WOMEN; CHEMOTHERAPY; EXPRESSION;
RISK; CARCINOMAS; GENE; POLYMORPHISMS; ASSOCIATION; PHENOTYPE
AB Background: Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype.
Methods and Findings: We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy.
Conclusions: The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required.
C1 [Blows, Fiona M.; Driver, Kristy E.; Provenzano, Elena; Dawson, Sarah-Jane; Dunning, Alison M.; Humphreys, Manjeet; Easton, Douglas F.; Caldas, Carlos; Pharoah, Paul D.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England.
[Schmidt, Marjanka K.; Broeks, Annegien; van Leeuwen, Flora E.; Wesseling, Jelle] Netherlands Canc Inst, Amsterdam, Netherlands.
[Cheang, Maggie C.; Gelmon, Karen; Nielsen, Torsten O.; Huntsman, David] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Cent Hosp, FIN-00290 Helsinki, Finland.
[Heikkila, Paivi] Univ Helsinki, Dept Pathol, Cent Hosp, FIN-00290 Helsinki, Finland.
[Heikkinen, Tuomas; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Akslen, Lars A.] Univ Bergen, Gade Inst, Sect Pathol, Haukeland Univ Hosp, Bergen, Norway.
[Begin, Louis R.] McGill Univ, Dept Pathol, Montreal, PQ, Canada.
[Begin, Louis R.] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada.
[Foulkes, William D.] McGill Univ, Program Canc Genet, Dept Oncol & Human Genet, Montreal, PQ, Canada.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Cafourek, Vicky; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[McLean, Catriona A.] Alfred Hosp, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[Rakha, Emad; Green, Andrew R.; Ellis, Ian O.] City Hosp Nottingham, Dept Histopathol, Breast Unit, NHS Trust, Nottingham, England.
[Rakha, Emad; Green, Andrew R.; Ellis, Ian O.] City Hosp Nottingham, Dept Surg, Nottingham, England.
[Rakha, Emad; Green, Andrew R.; Ellis, Ian O.] Univ Nottingham, Nottingham NG7 2RD, England.
[Sherman, Mark E.; Anderson, William F.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lissowska, Jolanta] Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Cox, Angela] Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Sch Med, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Reed, Malcolm W. R.] Univ Sheffield, Sch Med, Acad Unit Surg Oncol, Sheffield, S Yorkshire, England.
[Dunning, Alison M.; Humphreys, Manjeet; Easton, Douglas F.; Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Blows, FM (reprint author), Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England.
EM paul.pharoah@srl.cam.ac.uk
RI Caldas, Carlos/A-7543-2008; Garcia-Closas, Montserrat /F-3871-2015;
Akslen, Lars /C-1202-2017;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Akslen, Lars
/0000-0003-2710-9543; Dawson, Sarah-Jane/0000-0002-8276-0374; Cross,
Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799;
Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna,
Heli/0000-0002-0916-2976; foulkes, william/0000-0001-7427-4651; Cox,
Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099
FU Dutch Cancer Society [NKI 2001-2423, NKI 2007-3839]; Dutch National
Genomics Initiative; Helsinki University Central Hospital Research Fund,
Academy of Finland [110663]; Finnish Cancer Society; Sigrid Juselius
Foundation; Canadian Breast Cancer Research Alliance; US National
Institutes of Health [CA122340]; NIH [CA116201]; Australian NHMRC
[209057, 251553, 504711]; National Cancer Institute, Department of
Health and Human Services, USA; Yorkshire Cancer Research; Breast Cancer
Campaign; Cancer Research UK; UK NIHR Cambridge Biomedical Research
Centre; Cambridge Experimental Cancer Medicine Centre
FX Funding: Funding of the Amsterdam Breast Cancer Study was provided by
the Dutch Cancer Society (grants NKI 2001-2423; 2007-3839) and the Dutch
National Genomics Initiative. The Helsinki Breast Cancer Study has been
financially supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland (110663), the Finnish Cancer Society,
and the Sigrid Juselius Foundation. The immunohistochemical analysis of
cases from the Jewish General Hospital and Vancouver General Hospital
studies was funded by the Canadian Breast Cancer Research Alliance. The
Mayo Clinic Breast Cancer Study study was funded by US National
Institutes of Health grant CA122340 and an NIH Sponsored Program of
Research Excellence (SPORE) in Breast Cancer (CA116201). The
immunohistochemical analysis of breast cancers from the Melbourne
Collaborative Cohort Study was supported by Australian NHMRC grants
209057, 251553 and 504711 and infrastructure provided by The Cancer
Council Victoria. Polish Breast Cancer Study was funded by Intramural
Research Funds of the National Cancer Institute, Department of Health
and Human Services, USA. Sheffield Breast Cancer Study was supported by
Yorkshire Cancer Research and the Breast Cancer Campaign. The Study of
Epidemiology and Risk factors in Cancer Heredity is funded by a
programme grant from Cancer Research UK. The UK NIHR Cambridge
Biomedical Research Centre and the Cambridge Experimental Cancer
Medicine Centre support the work of EP, S-JD, CC, and PDP. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 34
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U1 1
U2 33
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD MAY
PY 2010
VL 7
IS 5
AR e1000279
DI 10.1371/journal.pmed.1000279
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608CV
UT WOS:000278560500013
PM 20520800
ER
PT J
AU Podgorski, CA
Langford, L
Pearson, JL
Conwell, Y
AF Podgorski, Carol A.
Langford, Linda
Pearson, Jane L.
Conwell, Yeates
TI Suicide Prevention for Older Adults in Residential Communities:
Implications for Policy and Practice
SO PLOS MEDICINE
LA English
DT Editorial Material
ID COMPLETED SUICIDE; NURSING-HOMES; LATER LIFE; DEPRESSION; BEHAVIOR;
RISK; FACILITIES
C1 [Podgorski, Carol A.] Univ Rochester, Dept Psychiat, Inst Family, Rochester, NY 14627 USA.
[Langford, Linda] Suicide Prevent Resource Ctr, Newton, MA USA.
[Pearson, Jane L.] NIMH, Div Serv Intervent Res, Bethesda, MD 20892 USA.
[Conwell, Yeates] Univ Rochester, Dept Psychiat, Ctr Study & Prevent Suicide, Rochester, NY USA.
RP Podgorski, CA (reprint author), Univ Rochester, Dept Psychiat, Inst Family, Rochester, NY 14627 USA.
EM carol_podgorski@urmc.rochester.edu
NR 30
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD MAY
PY 2010
VL 7
IS 5
AR e1000254
DI 10.1371/journal.pmed.1000254
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608CV
UT WOS:000278560500004
PM 20502523
ER
PT J
AU Hensley, LE
Mulangu, S
Asiedu, C
Johnson, J
Honko, AN
Stanley, D
Fabozzi, G
Nichol, ST
Ksiazek, TG
Rollin, PE
Wahl-Jensen, V
Bailey, M
Jahrling, PB
Roederer, M
Koup, RA
Sullivan, NJ
AF Hensley, Lisa E.
Mulangu, Sabue
Asiedu, Clement
Johnson, Joshua
Honko, Anna N.
Stanley, Daphne
Fabozzi, Giulia
Nichol, Stuart T.
Ksiazek, Thomas G.
Rollin, Pierre E.
Wahl-Jensen, Victoria
Bailey, Michael
Jahrling, Peter B.
Roederer, Mario
Koup, Richard A.
Sullivan, Nancy J.
TI Demonstration of Cross-Protective Vaccine Immunity against an Emerging
Pathogenic Ebolavirus Species
SO PLOS PATHOGENS
LA English
DT Article
ID NONHUMAN-PRIMATES; RHESUS-MONKEYS; HEMORRHAGIC-FEVER; VIRUS INFECTION;
CELL RESPONSES; T-LYMPHOCYTES; REPLICATION; VECTORS; GLYCOPROTEIN;
GENERATION
AB A major challenge in developing vaccines for emerging pathogens is their continued evolution and ability to escape human immunity. Therefore, an important goal of vaccine research is to advance vaccine candidates with sufficient breadth to respond to new outbreaks of previously undetected viruses. Ebolavirus (EBOV) vaccines have demonstrated protection against EBOV infection in nonhuman primates (NHP) and show promise in human clinical trials but immune protection occurs only with vaccines whose antigens are matched to the infectious challenge species. A 2007 hemorrhagic fever outbreak in Uganda demonstrated the existence of a new EBOV species, Bundibugyo (BEBOV), that differed from viruses covered by current vaccine candidates by up to 43% in genome sequence. To address the question of whether cross-protective immunity can be generated against this novel species, cynomolgus macaques were immunized with DNA/rAd5 vaccines expressing ZEBOV and SEBOV glycoprotein (GP) prior to lethal challenge with BEBOV. Vaccinated subjects developed robust, antigen-specific humoral and cellular immune responses against the GP from ZEBOV as well as cellular immunity against BEBOV GP, and immunized macaques were uniformly protected against lethal challenge with BEBOV. This report provides the first demonstration of vaccine-induced protective immunity against challenge with a heterologous EBOV species, and shows that Ebola vaccines capable of eliciting potent cellular immunity may provide the best strategy for eliciting cross-protection against newly emerging heterologous EBOV species.
C1 [Hensley, Lisa E.; Johnson, Joshua; Honko, Anna N.; Wahl-Jensen, Victoria] USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA.
[Mulangu, Sabue; Asiedu, Clement; Stanley, Daphne; Fabozzi, Giulia; Bailey, Michael; Sullivan, Nancy J.] NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nichol, Stuart T.; Ksiazek, Thomas G.; Rollin, Pierre E.] Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Atlanta, GA USA.
[Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Hensley, LE (reprint author), USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA.
EM nsullivan@nih.gov
OI Johnson, Joshua/0000-0002-5677-3841; Honko, Anna/0000-0001-9165-148X
FU Vaccine Research Center, NIAID, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the Vaccine Research Center, NIAID, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
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U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000904
DI 10.1371/journal.ppat.1000904
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900023
PM 20502688
ER
PT J
AU Hersperger, AR
Pereyra, F
Nason, M
Demers, K
Sheth, P
Shin, LY
Kovacs, CM
Rodriguez, B
Sieg, SF
Teixeira-Johnson, L
Gudonis, D
Goepfert, PA
Lederman, MM
Frank, I
Makedonas, G
Kaul, R
Walker, BD
Betts, MR
AF Hersperger, Adam R.
Pereyra, Florencia
Nason, Martha
Demers, Korey
Sheth, Prameet
Shin, Lucy Y.
Kovacs, Colin M.
Rodriguez, Benigno
Sieg, Scott F.
Teixeira-Johnson, Leia
Gudonis, Debbie
Goepfert, Paul A.
Lederman, Michael M.
Frank, Ian
Makedonas, George
Kaul, Rupert
Walker, Bruce D.
Betts, Michael R.
TI Perforin Expression Directly Ex Vivo by HIV-Specific CD8(+) T-Cells Is a
Correlate of HIV Elite Control
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOLYTIC EFFECTOR MOLECULES; IMMUNE
CONTROL; VIRAL LOAD; ANTIRETROVIRAL THERAPY; PROLIFERATIVE CAPACITY;
CYTOTOXIC GRANULES; UP-REGULATION; INFECTION; RESPONSES
AB Many immune correlates of CD8(+) T-cell-mediated control of HIV replication, including polyfunctionality, proliferative ability, and inhibitory receptor expression, have been discovered. However, no functional correlates using ex vivo cells have been identified with the known ability to cause the direct elimination of HIV-infected cells. We have recently discovered the ability of human CD8(+) T-cells to rapidly upregulate perforin-an essential molecule for cell-mediated cytotoxicity-following antigen-specific stimulation. Here, we examined perforin expression capability in a large cross-sectional cohort of chronically HIV-infected individuals with varying levels of viral load: elite controllers (n = 35), viremic controllers (n = 29), chronic progressors (n = 27), and viremic nonprogressors (n = 6). Using polychromatic flow cytometry and standard intracellular cytokine staining assays, we measured perforin upregulation, cytokine production, and degranulation following stimulation with overlapping peptide pools encompassing all proteins of HIV. We observed that HIV-specific CD8(+) T-cells from elite controllers consistently display an enhanced ability to express perforin directly ex vivo compared to all other groups. This ability is not restricted to protective HLA-B haplotypes, does not require proliferation or the addition of exogenous factors, is not restored by HAART, and primarily originates from effector CD8(+) T-cells with otherwise limited functional capability. Notably, we found an inverse relationship between HIV-specific perforin expression and viral load. Thus, the capability of HIV-specific CD8(+) T-cells to rapidly express perforin defines a novel correlate of control in HIV infection.
C1 [Hersperger, Adam R.; Demers, Korey; Makedonas, George; Betts, Michael R.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Nason, Martha] NIH, Biostat Res Branch, Bethesda, MD 20892 USA.
[Sheth, Prameet; Shin, Lucy Y.; Kaul, Rupert] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Kovacs, Colin M.] Canadian Immunodeficiency Res Collaborat, Toronto, ON, Canada.
[Rodriguez, Benigno; Sieg, Scott F.; Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Rodriguez, Benigno; Sieg, Scott F.; Lederman, Michael M.] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
[Teixeira-Johnson, Leia] Cleveland Clin, Dept Infect Dis, Cleveland, OH 44106 USA.
[Gudonis, Debbie; Frank, Ian] Univ Penn, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA.
[Goepfert, Paul A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Pereyra, Florencia; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
RP Hersperger, AR (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
EM betts@mail.med.upenn.edu
RI Rodriguez, Benigno/C-3365-2009
OI Rodriguez, Benigno/0000-0001-9736-7957
FU National Institutes of Health [R01 AI076066]
FX This study was funded in part through a grant from the National
Institutes of Health (R01 AI076066). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 167
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000917
DI 10.1371/journal.ppat.1000917
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900036
PM 20523897
ER
PT J
AU Hollingsworth, TD
Laeyendecker, O
Shirreff, G
Donnelly, CA
Serwadda, D
Wawer, MJ
Kiwanuka, N
Nalugoda, F
Collinson-Streng, A
Ssempijja, V
Hanage, WP
Quinn, TC
Gray, RH
Fraser, C
AF Hollingsworth, T. Deirdre
Laeyendecker, Oliver
Shirreff, George
Donnelly, Christl A.
Serwadda, David
Wawer, Maria J.
Kiwanuka, Noah
Nalugoda, Fred
Collinson-Streng, Aleisha
Ssempijja, Victor
Hanage, William P.
Quinn, Thomas C.
Gray, Ronald H.
Fraser, Christophe
TI HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai,
Uganda
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; MAXIMUM-LIKELIHOOD;
AIDS-PREVENTION; COMMUNITY TRIAL; SUBTYPE-A; INFECTION; PLASMA; RAXML;
DETERMINANTS
AB It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'). Individuals with suspected intra-couple transmission (97 couples) had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted) and the couple effect explained 16% of variance in viral loads (23% adjusted). The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted) and the size of the effect was 27% (37% adjusted). Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.
C1 [Hollingsworth, T. Deirdre; Shirreff, George; Donnelly, Christl A.; Fraser, Christophe] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England.
[Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Laeyendecker, Oliver; Collinson-Streng, Aleisha; Quinn, Thomas C.] NIAID, NIH, Baltimore, MD USA.
[Serwadda, David; Kiwanuka, Noah] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Serwadda, David; Wawer, Maria J.; Kiwanuka, Noah; Nalugoda, Fred; Ssempijja, Victor; Gray, Ronald H.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Hollingsworth, TD (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England.
EM c.fraser@imperial.ac.uk
RI Laeyendecker, Oliver/B-9331-2009; Shirreff, George/A-3775-2013;
Hollingsworth, Deirdre/D-2421-2009; Fraser, Christophe/A-8109-2008;
OI Hollingsworth, Deirdre/0000-0001-5962-4238; Fraser,
Christophe/0000-0003-2399-9657; Laeyendecker,
Oliver/0000-0002-6429-4760; Donnelly, Christl/0000-0002-0195-2463
FU Department of the Army, United States Army Medical Research and Material
Command Cooperative Agreement [DAMD17-98-2-8007]; National Institute of
Allergy and Infectious Diseases [R01 A134826, R01 A134265]; National
Institute of Child and Health Development [5P30HD06826]; Fogarty
Foundation [5D43TW00010]; Bill and Melinda Gates Institute for
Population and Reproductive Health at Johns Hopkins University; Royal
Society; Wellcome Trust; Medical Research Council; Division of
Intramural Research of the National Institute of Allergy and Infectious
Diseases, NIH; Imperial College Junior Research Fellowship; World Bank
STI Project, Uganda; Henry M. Jackson Foundation
FX We thank the Royal Society, the Wellcome Trust, the Medical Research
Council and the Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases, NIH for funding. TDH
gratefully acknowledges her Imperial College Junior Research Fellowship
for funding to perform this research. The Rakai study was funded through
the Department of the Army, United States Army Medical Research and
Material Command Cooperative Agreement DAMD17-98-2-8007; grants R01
A134826 and R01 A134265 from the National Institute of Allergy and
Infectious Diseases; grant 5P30HD06826 from the National Institute of
Child and Health Development; the World Bank STI Project, Uganda; the
Henry M. Jackson Foundation; a grant 5D43TW00010 from the Fogarty
Foundation; and the Bill and Melinda Gates Institute for Population and
Reproductive Health at Johns Hopkins University. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 37
TC 53
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U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000876
DI 10.1371/journal.ppat.1000876
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900002
PM 20463808
ER
PT J
AU Ireland, R
Olivares-Zavaleta, N
Warawa, JM
Gherardini, FC
Jarrett, C
Hinnebusch, BJ
Belisle, JT
Fairman, J
Bosio, CM
AF Ireland, Robin
Olivares-Zavaleta, Norma
Warawa, Jonathan M.
Gherardini, Frank C.
Jarrett, Clayton
Hinnebusch, B. Joseph
Belisle, John T.
Fairman, Jeffery
Bosio, Catharine M.
TI Effective, Broad Spectrum Control of Virulent Bacterial Infections Using
Cationic DNA Liposome Complexes Combined with Bacterial Antigens
SO PLOS PATHOGENS
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; LIVE VACCINE STRAIN; HUMAN MONONUCLEAR
PHAGOCYTES; FRANCISELLA-TULARENSIS LVS; REACTIVE NITROGEN; INTRACELLULAR
BACTERIUM; PROTECTIVE IMMUNITY; BURKHOLDERIA-PSEUDOMALLEI; EXPERIMENTAL
TULAREMIA; PNEUMONIC INFECTION
AB Protection against virulent pathogens that cause acute, fatal disease is often hampered by development of microbial resistance to traditional chemotherapeutics. Further, most successful pathogens possess an array of immune evasion strategies to avoid detection and elimination by the host. Development of novel, immunomodulatory prophylaxes that target the host immune system, rather than the invading microbe, could serve as effective alternatives to traditional chemotherapies. Here we describe the development and mechanism of a novel pan-anti-bacterial prophylaxis. Using cationic liposome non-coding DNA complexes (CLDC) mixed with crude F. tularensis membrane protein fractions (MPF), we demonstrate control of virulent F. tularensis infection in vitro and in vivo. CLDC+MPF inhibited bacterial replication in primary human and murine macrophages in vitro. Control of infection in macrophages was mediated by both reactive nitrogen species (RNS) and reactive oxygen species (ROS) in mouse cells, and ROS in human cells. Importantly, mice treated with CLDC+MPF 3 days prior to challenge survived lethal intranasal infection with virulent F. tularensis. Similarly to in vitro observations, in vivo protection was dependent on the presence of RNS and ROS. Lastly, CLDC+MPF was also effective at controlling infections with Yersinia pestis, Burkholderia pseudomallei and Brucella abortus. Thus, CLDC+MPF represents a novel prophylaxis to protect against multiple, highly virulent pathogens.
C1 [Ireland, Robin; Olivares-Zavaleta, Norma; Bosio, Catharine M.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Warawa, Jonathan M.; Gherardini, Frank C.; Jarrett, Clayton; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Belisle, John T.] Colorado State Univ, Dept Microbiol Immunol & Parasitol, Ft Collins, CO 80523 USA.
[Fairman, Jeffery] Juvaris Biotherapeut, Burlingame, CA USA.
RP Ireland, R (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015; Belisle, John/B-8944-2017
OI Belisle, John/0000-0002-2539-2798
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; Rocky Mountain Regional Center of Excellence NIH
[U54 AI065357]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases and the Rocky Mountain Regional Center of Excellence
NIH Grant U54 AI065357. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 57
TC 19
Z9 19
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000921
DI 10.1371/journal.ppat.1000921
PG 16
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900040
PM 20523903
ER
PT J
AU Li, H
Bar, KJ
Wang, SY
Decker, JM
Chen, YL
Sun, CX
Salazar-Gonzalez, JF
Salazar, MG
Learn, GH
Morgan, CJ
Schumacher, JE
Hraber, P
Giorgi, EE
Bhattacharya, T
Korber, BT
Perelson, AS
Eron, JJ
Cohen, MS
Hicks, CB
Haynes, BF
Markowitz, M
Keele, BF
Hahn, BH
Shaw, GM
AF Li, Hui
Bar, Katharine J.
Wang, Shuyi
Decker, Julie M.
Chen, Yalu
Sun, Chuanxi
Salazar-Gonzalez, Jesus F.
Salazar, Maria G.
Learn, Gerald H.
Morgan, Charity J.
Schumacher, Joseph E.
Hraber, Peter
Giorgi, Elena E.
Bhattacharya, Tanmoy
Korber, Bette T.
Perelson, Alan S.
Eron, Joseph J.
Cohen, Myron S.
Hicks, Charles B.
Haynes, Barton F.
Markowitz, Martin
Keele, Brandon F.
Hahn, Beatrice H.
Shaw, George M.
TI High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; SELECTIVE TRANSMISSION;
IN-VIVO; RECOMBINATION; CELLS; DYNAMICS; DIVERSITY; VARIANTS; PREVENT
AB Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3 -6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/ founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.
C1 [Li, Hui; Bar, Katharine J.; Wang, Shuyi; Decker, Julie M.; Chen, Yalu; Sun, Chuanxi; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Learn, Gerald H.; Schumacher, Joseph E.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Morgan, Charity J.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Hraber, Peter; Giorgi, Elena E.; Bhattacharya, Tanmoy; Korber, Bette T.; Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Giorgi, Elena E.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA.
[Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Eron, Joseph J.; Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Hicks, Charles B.; Haynes, Barton F.] Duke Univ, Dept Med, Durham, NC USA.
[Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Markowitz, Martin] Rockefeller Univ, New York, NY 10021 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
RP Li, H (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
EM gshaw@uab.edu
RI Bhattacharya, Tanmoy/J-8956-2013;
OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Korber,
Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897
FU Center for HIV/AIDS Vaccine Immunology (CHAVI); National Institutes of
Health [AI67854, AI27767, AI41534, AI28433, CA13148, RR24143,
HHSN266200400088C]; Bill & Melinda Gates Foundation [37874]
FX This work was supported by the Center for HIV/AIDS Vaccine Immunology
(CHAVI) and by grants and contracts from the National Institutes of
Health (AI67854, AI27767, AI41534, AI28433, CA13148, RR24143,
HHSN266200400088C) and the Bill & Melinda Gates Foundation (37874). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 60
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Z9 145
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000890
DI 10.1371/journal.ppat.1000890
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900012
PM 20485520
ER
PT J
AU Newman, ZL
Printz, MP
Liu, SH
Crown, D
Breen, L
Miller-Randolph, S
Flodman, P
Leppla, SH
Moayeri, M
AF Newman, Zachary L.
Printz, Morton P.
Liu, Shihui
Crown, Devorah
Breen, Laura
Miller-Randolph, Sharmina
Flodman, Pamela
Leppla, Stephen H.
Moayeri, Mahtab
TI Susceptibility to Anthrax Lethal Toxin-Induced Rat Death Is Controlled
by a Single Chromosome 10 Locus That Includes rNlrp1
SO PLOS PATHOGENS
LA English
DT Article
ID BACILLUS-ANTHRACIS; INFLAMMASOME COMPLEX; PROTECTIVE ANTIGEN; MOLECULAR
PLATFORM; MACROPHAGES; ACTIVATION; DISEASE; NALP1; SHOCK; MICE
AB Anthrax lethal toxin (LT) is a bipartite protease-containing toxin and a key virulence determinant of Bacillus anthracis. In mice, LT causes the rapid lysis of macrophages isolated from certain inbred strains, but the correlation between murine macrophage sensitivity and mouse strain susceptibility to toxin challenge is poor. In rats, LT induces a rapid death in as little as 37 minutes through unknown mechanisms. We used a recombinant inbred (RI) rat panel of 19 strains generated from LTsensitive and LT-resistant progenitors to map LT sensitivity in rats to a locus on chromosome 10 that includes the inflammasome NOD-like receptor (NLR) sensor, Nlrp1. This gene is the closest rat homolog of mouse Nlrp1b, which was previously shown to control murine macrophage sensitivity to LT. An absolute correlation between in vitro macrophage sensitivity to LT-induced lysis and animal susceptibility to the toxin was found for the 19 RI strains and 12 additional rat strains. Sequencing Nlrp1 from these strains identified five polymorphic alleles. Polymorphisms within the N-terminal 100 amino acids of the Nlrp1 protein were perfectly correlated with LT sensitivity. These data suggest that toxin-mediated lethality in rats as well as macrophage sensitivity in this animal model are controlled by a single locus on chromosome 10 that is likely to be the inflammasome NLR sensor, Nlrp1.
C1 [Newman, Zachary L.; Liu, Shihui; Crown, Devorah; Miller-Randolph, Sharmina; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, NIH, Bethesda, MD 20892 USA.
[Printz, Morton P.; Breen, Laura] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Flodman, Pamela] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA.
RP Newman, ZL (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov
FU National Heart Lung and Blood Institute [5PO1 HL35018]; NIH, National
Institute of Allergy and Infectious Diseases
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Allergy and Infectious Diseases and
grants from the National Heart Lung and Blood Institute (5PO1 HL35018 to
MPP). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 41
TC 41
Z9 44
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000906
DI 10.1371/journal.ppat.1000906
PG 8
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900025
PM 20502689
ER
PT J
AU Siebenga, JJ
Lemey, P
Pond, SLK
Rambaut, A
Vennema, H
Koopmans, M
AF Siebenga, J. Joukje
Lemey, Philippe
Pond, Sergei L. Kosakovsky
Rambaut, Andrew
Vennema, Harry
Koopmans, Marion
TI Phylodynamic Reconstruction Reveals Norovirus GII. 4 Epidemic Expansions
and their Molecular Determinants
SO PLOS PATHOGENS
LA English
DT Article
ID INFLUENZA-A VIRUS; ACUTE GASTROENTERITIS; UNITED-STATES; RECOMBINATION
DETECTION; EVOLUTIONARY DYNAMICS; HUMAN-POPULATIONS; OUTBREAKS;
SELECTION; NETHERLANDS; DIVERSITY
AB Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern.
C1 [Siebenga, J. Joukje; Vennema, Harry; Koopmans, Marion] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands.
[Siebenga, J. Joukje; Koopmans, Marion] Erasmus MC, Rotterdam, Netherlands.
[Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Leuven, Belgium.
[Pond, Sergei L. Kosakovsky] Univ Calif San Diego, Antiviral Res Ctr, San Diego, CA 92103 USA.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Siebenga, JJ (reprint author), Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands.
EM joukjes@yahoo.co.uk
RI Pond, Sergei/G-9830-2012;
OI Pond, Sergei/0000-0003-4817-4029; Rambaut, Andrew/0000-0003-4337-3707
FU European Commission [SP22-CT-2004-502571]; Flemish Science Foundation
(FWO) [G. 0513.06]; Joint DMS/NIGMS Mathematical Biology Initiative
[NSF-071499]; The Royal Society
FX The work of JJS was funded by the European Commission, Directorate
General Research Quality of Life program (EVENT [Enteric Virus
Emergence, New Tools] grant SP22-CT-2004-502571). PL was funded by a
postdoctoral fellowship from the Flemish Science Foundation (FWO) and
FWO grant G. 0513.06. SLKP was supported by the Joint DMS/NIGMS
Mathematical Biology Initiative through Grant NSF-071499. AR was
supported by The Royal Society. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 69
TC 87
Z9 88
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000884
DI 10.1371/journal.ppat.1000884
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900008
PM 20463813
ER
PT J
AU Weiss, GE
Traore, B
Kayentao, K
Ongoiba, A
Doumbo, S
Doumtabe, D
Kone, Y
Dia, S
Guindo, A
Traore, A
Huang, CY
Miura, K
Mircetic, M
Li, SP
Baughman, A
Narum, DL
Miller, LH
Doumbo, OK
Pierce, SK
Crompton, PD
AF Weiss, Greta E.
Traore, Boubacar
Kayentao, Kassoum
Ongoiba, Aissata
Doumbo, Safiatou
Doumtabe, Didier
Kone, Younoussou
Dia, Seydou
Guindo, Agnes
Traore, Abdramane
Huang, Chiung-Yu
Miura, Kazutoyo
Mircetic, Marko
Li, Shanping
Baughman, Amy
Narum, David L.
Miller, Louis H.
Doumbo, Ogobara K.
Pierce, Susan K.
Crompton, Peter D.
TI The Plasmodium falciparum-Specific Human Memory B Cell Compartment
Expands Gradually with Repeated Malaria Infections
SO PLOS PATHOGENS
LA English
DT Article
ID DELTA T-CELLS; IMMUNOLOGICAL MEMORY; YELLOW-FEVER; PLASMA-CELLS;
ANTIBODY-RESPONSES; GERMINAL CENTER; ENDEMIC AREA; BONE-MARROW;
IN-VITRO; VACCINE
AB Immunity to Plasmodium falciparum (Pf) malaria is only acquired after years of repeated infections and wanes rapidly without ongoing parasite exposure. Antibodies are central to malaria immunity, yet little is known about the B-cell biology that underlies the inefficient acquisition of Pf-specific humoral immunity. This year-long prospective study in Mali of 185 individuals aged 2 to 25 years shows that Pf-specific memory B-cells and antibodies are acquired gradually in a stepwise fashion over years of repeated Pf exposure. Both Pf-specific memory B cells and antibody titers increased after acute malaria and then, after six months of decreased Pf exposure, contracted to a point slightly higher than pre-infection levels. This inefficient, stepwise expansion of both the Pf-specific memory B-cell and long-lived antibody compartments depends on Pf exposure rather than age, based on the comparator response to tetanus vaccination that was efficient and stable. These observations lend new insights into the cellular basis of the delayed acquisition of malaria immunity.
C1 [Weiss, Greta E.; Mircetic, Marko; Li, Shanping; Baughman, Amy; Pierce, Susan K.; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Dia, Seydou; Guindo, Agnes; Traore, Abdramane; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Miura, Kazutoyo; Narum, David L.; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA.
RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM spierce@niaid.nih.gov; pcrompton@niaid.nih.gov
RI Crompton, Peter/N-1130-2016
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases (NIAID), 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 71
TC 86
Z9 86
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2010
VL 6
IS 5
AR e1000912
DI 10.1371/journal.ppat.1000912
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 610TL
UT WOS:000278759900031
PM 20502681
ER
PT J
AU Silverman, MN
Heim, CM
Nater, UM
Marques, AH
Sternberg, EM
AF Silverman, Marni N.
Heim, Christine M.
Nater, Urs M.
Marques, Andrea H.
Sternberg, Esther M.
TI Neuroendocrine and Immune Contributors to Fatigue
SO PM&R
LA English
DT Article
AB Central fatigue, a persistent and subjective sense of tiredness, generally correlates poorly with traditional markers of disease. It is frequently associated with psychosocial factors, such as depression, sleep disorder, anxiety, and coping style, which suggest that dysregulation of the body's stress systems may serve as an underlying mechanism in the maintenance of chronic fatigue (CF). This article addresses the endocrine, neural, and immune factors that contribute to fatigue and describes research regarding the role of these factors in chronic fatigue syndrome as a model for addressing the biology of CF. In general, hypoactivity of the hypothalamic-pituitary-adrenal axis, autonomic nervous system alterations characterized by sympathetic overactivity and low vagal tone, as well as immune abnormalities, may contribute to the expression of CF. Noninvasive methods for evaluating endocrine, neural, and immune function are also discussed. Simultaneous evaluation of neuroendocrine and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems, their role in disease susceptibility, and progression of stress-related disorders. PM R 2010;2:338-346
C1 [Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Integrat Neural Immune Program, Rockville, MD 20852 USA.
[Heim, Christine M.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Nater, Urs M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Nater, Urs M.] Univ Zurich, Dept Clin Psychol & Psychotherapy, CH-8006 Zurich, Switzerland.
[Marques, Andrea H.] NIMH, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Integrat Neural Immune Program, 5625 Fishers Lane,MSC-9401, Rockville, MD 20852 USA.
EM sternbee@mail.nih.gov
RI Heim, Christine/A-1183-2009; Nater, Urs/J-6898-2013;
OI Nater, Urs/0000-0002-2430-5090
FU NIH Intramural Research Funds; CeNeRx; NIH Intramural Research Funds,
Department of Defense
FX 8B, NIH Intramural Research Funds; 2A, CeNeRx consulting fee; 7A,
Novartis; 8B, NIH, NARSAD, ADAA; 8B, NIH Intramural Research Funds,
Department of Defense
NR 109
TC 49
Z9 50
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 338
EP 346
DI 10.1016/j.pmrj.2010.04.008
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400005
PM 20656615
ER
PT J
AU Mitchell, SA
AF Mitchell, Sandra A.
TI Cancer-Related Fatigue: State of the Science
SO PM&R
LA English
DT Article
AB Cancer-related fatigue (CRF) is a disabling and distressing symptom that is highly prevalent across the cancer continuum from a patient's diagnosis and treatment through, survivorship and end of life. It has a multifactorial etiology and significant individual variability in its clinical expression, determinants, and sequelae. Despite the significance of CRF, it is often underdiagnosed, and management is frequently suboptimal. This review synthesizes the state of the science concerning the features, possible mechanisms, and predictors of CRF; offers recommendations for the evaluation of CRF; and appraises the strength of the evidence for a wide range of pharmacologic and nonpharrnacologic interventions to prevent and manage fatigue during and after cancer and its treatment. There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. Rigorously designed and adequately powered randomized trials are warranted to (1) determine the effectiveness of promising approaches and (2) identify the interventions that are most effective in treating CRF in specific subpopulations (eg, stem cell transplant recipients, older adults, patients with lung or colorectal cancers, survivors, and those at the end of life). Studies to elucidate the biologic expression profiles of CRF, to explicate the mechanisms through which particular interventions impact CRF, and to identify the mediators and moderators of fatigue outcomes will ultimately permit individually tailored approaches for the treatment of CRF. PM R 2010;2:364-383
C1 NIH, Ctr Clin, Bethesda, MD 20852 USA.
RP Mitchell, SA (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Suite 2 B11, Bethesda, MD 20852 USA.
EM mitchlls@mail.nih.gov
FU Clinical Center, National Institutes of Health, Bethesda, MD
FX This work was supported by the Clinical Center, National Institutes of
Health, Bethesda, MD.
NR 331
TC 55
Z9 57
U1 6
U2 30
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 364
EP 383
DI 10.1016/j.pmrj.2010.03.024
PG 20
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400008
PM 20656618
ER
PT J
AU Kaltsas, G
Vgontzas, A
Chrousos, G
AF Kaltsas, Gregory
Vgontzas, Alexandros
Chrousos, George
TI Fatigue, Endocrinopathies, and Metabolic Disorders
SO PM&R
LA English
DT Article
AB Fatigue is a frequent reason for seeking medical attention. Endocrine dysfunction is a common etiology of fatigue. In fact, thyroid function is usually one of the first explanations on the list of possible diagnoses. The symptoms associated with endocrinopathies are frequently "nonspecific," and psychiatric disease or psychological disorders need to be differentiated. Often, this can be accomplished using biological measures of hormone function, such as measures of thyroid, pituitary, parathyroid, and adrenal hormone levels. The field of endocrinology is highly dependent on an algorithmic approach to differential diagnosis using hormone levels as the guide. The use of self-reports helps identify at-risk patients, and raises suspicions about whether there is an abnormality, but diagnosis is dependent on laboratory values. Metabolic abnormalities, such as hyper- or hypoglycemia, dyslipidemia, and gonadal dysfunction can also contribute to fatigue. A better understanding of the interactions among hormones, their releasing factors, and regulation of inflammation will help identify abnormalities early and help distinguish endocrinopathies from other causes of fatigue. Early identification of these abnormalities may reduce end-organ damage and improve treatment strategies. PM R 2010;2:393-398
C1 [Kaltsas, Gregory] Natl Tech Univ Athens, Dept Pathophysiol, Athens, Greece.
[Chrousos, George] Natl Tech Univ Athens, Dept Pediat, Athens, Greece.
[Vgontzas, Alexandros] Penn State Univ, Hershey Med Sch, Hershey, PA USA.
RP Chrousos, G (reprint author), NIH, 6705 Rockledge Dr,Room 8000,MSC 7970, Bethesda, MD 20892 USA.
EM chrousog@mail.nih.gov
NR 22
TC 14
Z9 17
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 393
EP 398
DI 10.1016/j.pmrj.2010.04.011
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400010
PM 20656620
ER
PT J
AU Cantor, F
AF Cantor, Fredric
TI Central and Peripheral Fatigue: Exemplified by Multiple Sclerosis and
Myasthenia Gravis
SO PM&R
LA English
DT Article
AB Fatigue is a feature of several chronic diseases of the central and peripheral nervous system. The pathophysiology of central fatigue is complex and often not well-defined. In contrast, peripheral fatigue is more objectively defined and measured. Fatigue can be part of the primary disease process, but there are often contributions from comorbid factors such as depression, sleep disturbance, medication, or deconditioning. Multiple sclerosis (MS) offers an example of central fatigue. More than 40% of MS patients complain of fatigue. Validated questionnaires are used to assess fatigue severity and comorbid factors. Although fatigue is believed to be a primary process in MS, depression and sleep disturbance are often comorbid problems. Magnetic resonance imaging (MRI), positron emission tomography, and functional MRI studies suggest that fatigue is related to gray matter disease, particularly of the cerebral cortex, but also of the thalamus and caudate. Disruption of impulse propagation from demyelination is also a likely factor. It is uncertain if proinflammatory cytokines have a specific effect on the genesis of MS fatigue. Several medications have been reported to alleviate fatigue in MS, but controlled studies show contradictory results. Treatment of depression and sleep disturbance, use of exercise programs and rehabilitation therapies as well as treatment of other comorbid conditions is necessary for optimal alleviation of fatigue. Myasthenia gravis (MG) patients exhibit peripheral fatigue. In contrast to MS, the mechanism of weakness and fatigue in MG is well-defined. Antibodies to the postsynaptic acetylcholine receptor at the myoneural junction cause diminution of the force of muscle contractions. This leads to a feeling of fatigue. MG treatments increase the availability of acetylcholine and reduce antibody formation. Evaluation for comorbid conditions, especially thymoma and hyperthyroidism, are mandatory in patients with MG. PM R 203 0;2:399-405
C1 NINDS, NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA.
RP Cantor, F (reprint author), NINDS, NIH, Neuroimmunol Branch, 10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA.
EM cantorf@ninds.nih.gov
NR 65
TC 18
Z9 18
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 399
EP 405
DI 10.1016/j.pmrj.2010.04.012
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400011
PM 20656621
ER
PT J
AU Eldadah, BA
AF Eldadah, Basil A.
TI Fatigue and Fatigability in Older Adults
SO PM&R
LA English
DT Article
AB Fatigue is believed to be a common complaint among older adults; however, multiple studies of self-reported fatigue across the lifespan have found this may not be the case. To explain this paradox, this article considers "fatigability"-a phenotype characterized by the relationship between an individual's perceived fatigue and the activity level with which the fatigue is associated. Fatigability may be measured by combining self-report measures of fatigue with performance of physical or cognitive activities, provided that the work of the activity is known or can be standardized. Doing so prevents self-pacing and allows meaningful comparisons across subjects and between studies. Increased fatigability with aging may arise from a variety of factors including age-related changes in energy production or utilization, and inflammatory mechanisms. A few published intervention studies have targeted fatigue in older adults, though none have examined fatigability specifically. Because fatigue may represent a physiologic warning system, future clinical studies may benefit from a focus on fatigability, where both symptoms and function are considered. PM R 2010;2:406-413
C1 NCI, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
RP Eldadah, BA (reprint author), NCI, Div Geriatr & Clin Gerontol, 7201 Wisconsin Ave,3C307, Bethesda, MD 20892 USA.
EM eldadahb@nia.nih.gov
NR 79
TC 47
Z9 47
U1 2
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 406
EP 413
DI 10.1016/j.pmrj.2010.03.022
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400012
PM 20656622
ER
PT J
AU Zlott, DA
Byrne, M
AF Zlott, Daniel A.
Byrne, Mary
TI Mechanisms by Which Pharmacologic Agents May Contribute to Fatigue
SO PM&R
LA English
DT Article
AB Fatigue is a common side effect of medications. This review summarizes some of the mechanisms by which drugs may cause fatigue. One major mechanism by which medications can cause fatigue is by central nervous system (CNS) depression. CNS depression can result from decreased excitatory activity, as is commonly seen with some anticholinergic agents, centrally acting alpha-agonists, and anticonvulsants. CNS depression can also result from increased inhibitory activity within the CNS, as is seen with benzodiazepines and barbiturates, which augment the effects of the inhibitory neurotransmitter, gamma-aminobutyric acid. Opioids also increase inhibitory CNS activity through their interactions with the various subtypes of opioid receptors. Acting outside of the CNS, medications may cause fatigue as a result of either a true or a functional anemia by a number of mechanisms. Bone marrow toxicity, which results in decreased hematopoiesis, is such a mechanism. This is commonly seen with antineoplastics agents, but can also be observed in association with a wide variety of medication classes, including anticonvulsants, antidepressants, and antimicrobial agents. Another way that medications can cause anemia is by increased red blood cell destruction, as is seen with immune hemolytic anemia. Additionally, medications may cause a functional anemia through alteration of the heme group within the hemoglobin molecule, as is seen in methemoglobinemia. Finally, many drugs, including placebos, cause fatigue by unknown mechanisms. In addition to causing fatigue, some medications may be used to help relieve fatigue, although this drug class is limited in number at this point in time. PM R 2010;2:451-455
C1 [Zlott, Daniel A.; Byrne, Mary] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
RP Zlott, DA (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1N-257 MSC-1196,10 Ctr Dr, Bethesda, MD 20892 USA.
EM zlottd@mail.nih.gov
NR 28
TC 19
Z9 19
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2010
VL 2
IS 5
BP 451
EP 455
DI 10.1016/j.pmrj.2010.04.018
PG 5
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23SB
UT WOS:000208361400017
PM 20656627
ER
PT J
AU Yuan, LX
Sun, LG
Long, NY
Xie, ZQ
Wang, YH
Liu, XD
AF Yuan, Linxi
Sun, Liguang
Long, Nanye
Xie, Zhouqing
Wang, Yuhong
Liu, Xiaodong
TI Seabirds colonized Ny-lesund, Svalbard, Arctic similar to 9,400 years
ago
SO POLAR BIOLOGY
LA English
DT Article
DE Paleo-notch; Sediment; Seabird; Colonize; Ny-Alesund
ID LAST GLACIAL MAXIMUM; FRANZ JOSEF LAND; LAKE-SEDIMENTS; POSTGLACIAL
EMERGENCE; CONTAMINANT RESIDUES; GEOCHEMICAL EVIDENCE; PENGUIN
POPULATIONS; HISTORICAL TRENDS; SEAL POPULATIONS; WESTERN SVALBARD
AB A 118-cm-long and well-preserved sediment profile in a paleo-notch, which was formed by ocean wave action before rising to the terrace, was collected from the first terrace of Ny-lesund, Svalbard, Arctic. The bottom of this profile was dated as 9,400 years B.P. based on two radiocarbon dates of fossil mollusc shell fragments. The organic material in the sediment was identified by delta(13)C(org)-C/N plot and delta(15)N(org) characteristics to be predominantly composed of seabird guano, which was transported from the ocean via preying and excreting by seabirds. These results indicate that seabirds have inhabited Ny-lesund since 9,400 years B.P. after Kongsfjorden was completely deglaciated. This is the first report on Holocene seabird occupation on Ny-lesund and it provides the foundation for understanding the ecological history of seabirds in Svalbard in Holocene.
C1 [Yuan, Linxi; Sun, Liguang; Xie, Zhouqing; Liu, Xiaodong] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
[Long, Nanye] Univ Wisconsin, Dept Anim Sci, Madison, WI 53706 USA.
[Wang, Yuhong] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
EM slg@ustc.edu.cn
FU National Science Foundation of China [NSFC 40676004, 40730107]; Key
Projects in the National Science and Technology Pillar Program
[2006BAB18B07]; National 973 Program [2009CB421605]
FX We appreciate Prof. Steven D. Emslie for helpful revision to improve
this manuscript. Special thanks to Prof. Fridtjof Mehlum for helpful
discussion during Arctic Science Submit Week 2009 (ASSW2009). We also
thank Prof. John P. Smol, Prof. Dominic A. Hodgson and an anonymous
reviewer for their valuable critical comments in improving the
manuscript. Authors wish to thank the Chinese Arctic and Antarctic
Administration (CAAA) for supporting. This research was funded by
National Science Foundation of China (Grants NSFC 40676004 and
40730107), Key Projects in the National Science and Technology Pillar
Program (2006BAB18B07), and National 973 Program (2009CB421605).
NR 55
TC 13
Z9 13
U1 3
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0722-4060
J9 POLAR BIOL
JI Polar Biol.
PD MAY
PY 2010
VL 33
IS 5
BP 683
EP 691
DI 10.1007/s00300-009-0745-8
PG 9
WC Biodiversity Conservation; Ecology
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 582RF
UT WOS:000276615400012
ER
PT J
AU Breslau, ES
Rochester, PW
Saslow, D
Crocoll, CE
Johnson, LE
Vinson, CA
AF Breslau, Erica S.
Rochester, Phyllis W.
Saslow, Debbie
Crocoll, Caroline E.
Johnson, Lenora E.
Vinson, Cynthia A.
TI Developing Partnerships to Reduce Disparities in Cancer Screening
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
AB Background
Interventions in scientific settings to improve the wellbeing of women who are not regularly screened for cancer have failed. Consequently, community-based prevention and control efforts are needed.
Community Context
From 2003 through 2007, three federal agencies and 1 nongovernmental agency collaborated with county-level public health counterparts from 6 states to address screening disparities in cervical and breast cancer in counties with the highest prevalence. This case study describes lessons learned from Team Up, a model pilot program.
Methods
We conducted a descriptive qualitative case study including 5 Southern states and 1 Midwestern state: Alabama, Georgia, Kentucky, Missouri, South Carolina, and Tennessee. The 6 states underwent a 5-step process to adopt, adapt, and implement 1 of 3 evidence-based interventions designed for cervical and breast cancer screening.
Outcome
The 6 participating states had various levels of success. Participating states formed and sustained viable interorganizational public health partnerships throughout the pilot program and beyond.
Interpretation
Although this innovative pilot faced many difficulties, participants overcame substantial obstacles and produced many key accomplishments. Team Up brought together 2 challenging public health strategies: the translation of evidence-based approaches to communities and populations, and partnerships among diverse people and organizations. Case study results suggest that using a mix of approaches can promote the transference of evidence from research into practice through local, regional, and national partnerships.
C1 [Rochester, Phyllis W.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Saslow, Debbie] Amer Canc Soc, Atlanta, GA 30329 USA.
[Crocoll, Caroline E.] USDA, Washington, DC 20250 USA.
[Breslau, Erica S.; Johnson, Lenora E.; Vinson, Cynthia A.] NCI, Bethesda, MD 20850 USA.
RP Breslau, ES (reprint author), NCI, 6130 Execut Blvd,Ste 4098, Bethesda, MD 20850 USA.
EM breslaue@mail.nih.gov
NR 25
TC 4
Z9 4
U1 2
U2 4
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD MAY
PY 2010
VL 7
IS 3
AR A62
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V20SB
UT WOS:000208158600017
PM 20394701
ER
PT J
AU Althoff, KN
Anastos, K
Nelson, KE
Celentano, DD
Sharp, GB
Greenblatt, RM
French, AL
Diamond, DJ
Holman, S
Young, M
Gange, SJ
AF Althoff, Keri N.
Anastos, Kathryn
Nelson, Kenrad E.
Celentano, David D.
Sharp, Gerald B.
Greenblatt, Ruth M.
French, Audrey L.
Diamond, Don J.
Holman, Susan
Young, Mary
Gange, Stephen J.
TI Predictors of reported influenza vaccination in HIV-infected women in
the United States, 2006-2007 and 2007-2008 seasons
SO PREVENTIVE MEDICINE
LA English
DT Article
DE HIV/AIDS; Highly active antiretroviral therapy; Influenza vaccine;
Vaccine coverage; Multi-center study; Cohort study; United States;
Adult; Female
ID HEALTH BELIEF MODEL; INTERAGENCY HIV; PREVALENCE; VIRUS; MORTALITY;
EFFICACY; RATIOS; ADULTS; HOSPITALIZATIONS; IMMUNIZATION
AB Objective. To estimate the cumulative incidence of self-reported influenza vaccination ("vaccination coverage") and investigate predictors in HIV-infected women.
Methods. In an ongoing cohort study of HIV-infected women in five US cities, data from two influenza seasons (2006-2007 n = 1209 and 2007-2008 n = 1161) were used to estimate crude and adjusted prevalence ratios (aPR) and 95% confidence intervals ([.]) from Poisson regression with robust variance models using generalized estimating equations (GEE).
Results. In our study, 55% and 57% of HIV-infected women reported vaccination during the 2006-2007 and 2007-2008 seasons, respectively. Using data from both seasons, older age, non-smoking status, CD4 T-lymphocyte (CD4) count >= 200 cells/mm(3), and reporting at least one recent healthcare visit was associated with increased vaccination coverage. In the 2007-2008 season, a belief in the protection of the vaccine (aPR = 1.38 [1.18, 1.61]) and influenza vaccination in the previous season (aPR = 1.66 [1.44, 1.91]) most strongly predicted vaccination status.
Conclusion. Interventions to reach unvaccinated HIV-infected women should focus on changing beliefs about the effectiveness of influenza vaccination and target younger women, current smokers, those without recent healthcare visits, or a CD4 count <200 cells/mm(3). (C) 2010 Elsevier Inc. All rights reserved.
C1 [Althoff, Keri N.; Nelson, Kenrad E.; Celentano, David D.; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Dept Epidemiol, Bronx, NY 10467 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[French, Audrey L.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[French, Audrey L.] John H Stroger Jr Hosp Cook Cty, Chicago, IL 60612 USA.
[Diamond, Don J.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Holman, Susan] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA.
[Young, Mary] Georgetown Univ, Dept Med, Washington, DC 20007 USA.
RP Althoff, KN (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM kalthoff@jhsph.edu; kanastos@verizon.net; kenelson@jhsph.edu;
dcelenta@jhsph.edu; gsharp@niaid.nih.gov; ruth.greenblatt@ucsf.edu;
audrey_french@rush.edu; ddiamond@coh.org; susan.holman@downstate.edu;
youngma@georgetown.edu; sgange@jhsph.edu
OI Gange, Stephen/0000-0001-7842-512X; Diamond, Don/0000-0003-3579-7083
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
National Institute of Child Health and Human Development [UO1-HD-32632];
National Cancer Institute; National Institute on Drug Abuse; National
Institute on Deafness and Other Communication Disorders; National Center
for Research Resources [UCSF-CTSI] [UL1 RR024131]; Johns Hopkins
Training Program in Sexually Transmitted Infections [T32-AI050056]
FX The WIHS is funded by the National Institute of Allergy and Infectious
Diseases [grant numbers UO1-AI-35004, UO1-AI-31834, UO1-AI-34994,
UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590]; the National Institute of
Child Health and Human Development [grant number UO1-HD-32632]. The
study is co-funded by the National Cancer Institute; the National
Institute on Drug Abuse; and the National Institute on Deafness and
Other Communication Disorders. Funding is also provided by the National
Center for Research Resources [UCSF-CTSI grant number UL1 RR024131]. The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health. This work was also supported by the Johns
Hopkins Training Program in Sexually Transmitted Infections
[T32-AI050056] to [KNA].
NR 40
TC 7
Z9 8
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD MAY-JUN
PY 2010
VL 50
IS 5-6
BP 223
EP 229
DI 10.1016/j.ypmed.2010.03.007
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 600EL
UT WOS:000277967300001
PM 20303362
ER
PT J
AU Ramkumar, HL
Zhang, J
Chan, CC
AF Ramkumar, Hema L.
Zhang, Jun
Chan, Chi-Chao
TI Retinal ultrastructure of murine models of dry age-related macular
degeneration (AMD)
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; AMD Dry Mouse model; Retina;
Ultrastructure Pathology
ID COMPLEMENT FACTOR-H; SENESCENCE-ACCELERATED MOUSE; BASAL LAMINAR
DEPOSIT; HIGH-FAT DIET; MANGANESE SUPEROXIDE-DISMUTASE; MONKEY
MACACA-FASCICULARIS; SORSBYS FUNDUS DYSTROPHY; ALZHEIMERS-DISEASE BRAIN;
PIGMENT EPITHELIAL-CELLS; FRIZZLED-RELATED PROTEIN
AB Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of macular degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch's membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr(-/-) (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1R345W/(R345W) (Doyne honeycomb retinal dystrophy), and Timp3(s156C/S156C) (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh2(-/-), Ccl2(-/-), and Ccr2(-/-), Cx3cr1(-/-), oxidative stress associated genes such as Sod1(-/-) and Sod2 knockdown, metabolic pathway genes such as neprilysirri(-/-) (amyloid 13), transgenic mcd/mcd (cathepsin D), Cp(-/-)/Heph(-/Y) (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically manipulated by immunization with carboxyethylpyrrole (CEP), an oxidative fragment of DHA found in drusen, and found to present with dry AMD features. Third, natural mouse strains such as arrd2/arrd2 (Mdm gene mutation) and the senescence accelerated mice (SAM) spontaneously develop features of dry AMD like photoreceptor atrophy and thickening of Bruch's membrane.
All the aforementioned models develop retinal lesions with various features that simulate dry AMD lesions: focal photoreceptor degeneration, abnormal RPE with increased lipofuscin, basal infolding, decreased melanosomes and degeneration. However, Bruch's membrane changes are less common. Most mice develop retinal lesions at an older age (6-24 months, depending on the models), while the Cc12(-/-)/x3cr1(-/-) mice develop lesions by 4-6 weeks. Although murine models present various degrees of retinal and/or RPE degeneration, classical drusen is extremely rare. Using electron microscopy, small drusenoid deposits are found between RPE and Bruch's membrane in a few models including Efemp1(R345W/R345W), Ccl2(-/-)/cx3cr1(-/-), neprilysin(-/-), transgenic mcd/mcd, and ApoE4 transgenic mice on a high fat diet. High A2E levels are measured in the retinas of abcr(-/-), transgenic ELOVL4, and Ccl2(-/-)/cx3cr1(-/-) mice. In summary, murine models provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease. This review compares the major dry AMD murine models and discusses retinal pathology at the ultrastructural level. Published by Elsevier Ltd.
C1 [Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ramkumar, Hema L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Ramkumar, Hema L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 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
RI Zhang, Jun/K-2424-2012;
OI Ramkumar, Hema/0000-0002-1452-0694
FU NEI Intramural Research Program; Howard Hughes Medical Institute
FX The NEI Intramural Research Program and Howard Hughes Medical Institute
provided support. Dr. Robert B. Nussenblatt offered his insight into the
challenges of AMD research in mice and men.
NR 231
TC 61
Z9 64
U1 0
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD MAY
PY 2010
VL 29
IS 3
BP 169
EP 190
DI 10.1016/j.preteyeres.2010.02.002
PG 22
WC Ophthalmology
SC Ophthalmology
GA 598HT
UT WOS:000277826800001
PM 20206286
ER
PT J
AU Kristal, AR
Price, DK
Till, C
Schenk, JM
Neuhouser, ML
Ockers, S
Lin, DW
Thompson, IM
Figg, WD
AF Kristal, Alan R.
Price, Douglas K.
Till, Cathee
Schenk, Jeannette M.
Neuhouser, Marian L.
Ockers, Sandy
Lin, Daniel W.
Thompson, Ian M.
Figg, William D.
TI Androgen Receptor CAG Repeat Length Is Not Associated With the Risk of
Incident Symptomatic Benign Prostatic Hyperplasia: Results From the
Prostate Cancer Prevention Trial
SO PROSTATE
LA English
DT Article
DE benign prostatic hyperplasia; androgen receptor CAG repeat length; lower
urinary tract symptoms; steroid hormones
ID SERUM TESTOSTERONE LEVELS; ELDERLY-MEN; POLYMORPHISM; GENE; SURGERY;
OBESITY; LEPTIN; MASS
AB BACKGROUND. To examine whether androgen receptor (AR) CAG repeat length was associated with the risk of incident benign prostatic hyperplasia (BPH).
METHODS. A nested case-control study of 416 BPH cases and 527 controls drawn from Prostate Cancer Prevention Trial placebo-arm participants who were free of BPH at baseline. BPH was assessed over 7 years and was defined as receipt of medical or surgical treatment, two scores > 14 on the International Prostate Symptom Score (IPSS), or two increases in IPSS >= 5 with at least one score >= 12.
RESULTS. Compared to men with AR repeat length <= 19, the covariate-adjusted odds ratios [95% CI] were 1.07 [0.73, 1.57] and 0.90 [0.55, 1.45]) for repeat length 20-24 and >= 25, respectively. There was a weak association of AR repeat length with baseline serum testosterone (T) (Spearman r = 0.09, p <0.02); however, control for or stratification by T did not change study results. Further, results did not differ when stratified by body mass index or baseline concentration of 3 alpha-diol glucoronide, and were similar for all BPH definitions.
CONCLUSIONS. There were no associations of AR CAG repeat length and BPH risk. Knowledge of AR CAG repeat length provides no clinical useful information for the prevention of symptomatic BPH. Prostate 70: 584-590, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Kristal, Alan R.; Till, Cathee; Schenk, Jeannette M.; Neuhouser, Marian L.; Lin, Daniel W.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA.
[Kristal, Alan R.; Schenk, Jeannette M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Price, Douglas K.; Ockers, Sandy; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Lin, Daniel W.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
RP Kristal, AR (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, POB 19024,M4-B402, Seattle, WA 98109 USA.
EM akristal@fhcrc.org
RI Figg Sr, William/M-2411-2016;
OI Kristal, Alan/0000-0002-7329-1617
FU NCI NIH HHS [P01 CA108964]; NIDDK NIH HHS [R01 DK063303]
NR 21
TC 12
Z9 13
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2010
VL 70
IS 6
BP 584
EP 590
DI 10.1002/pros.21092
PG 7
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 593ST
UT WOS:000277481700002
PM 19938041
ER
PT J
AU Stevens, VL
Ahn, J
Sun, JZ
Jacobs, EJ
Moore, SC
Pate, AV
Berndt, SI
Albanes, D
Hayes, RB
AF Stevens, Victoria L.
Ahn, Jiyoung
Sun, Juzhong
Jacobs, Eric J.
Moore, Steven C.
Pate, Alpa V.
Berndt, Sonja I.
Albanes, Demetrius
Hayes, Richard B.
TI HNF1B and JAZF1 Genes, Diabetes, and Prostate Cancer Risk
SO PROSTATE
LA English
DT Article
DE prostate cancer; diabetes; genes; prospective study
ID CHOLESTEROL-LOWERING DRUGS; STATIN USE; ANTIGEN LEVELS; CELL-GROWTH;
COHORT; HEALTH; METAANALYSIS; PROGRESSION; INHIBITION; PREVENTION
AB BACKGROUND. Epidemiologic studies have shown that men with type II diabetes have a lower risk of prostate cancer than non-diabetic men. Recently, common variants in two genes, HNF1B and JAZF1 were found to be associated with both of these diseases.
METHODS. We examined whether the relationship between HNF1B and JAZF1 variants and decreased prostate cancer risk may potentially be mediated through diabetes in two large prospective studies, the Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
RESULTS. Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes. The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. All five SNP prostate cancer relationships did not substantially differ when the analyses were stratified by diabetic status or when diabetic status was controlled for in the model. Furthermore, the association of diabetes with prostate cancer was not altered when the SNPs were included in the logistic model.
CONCLUSIONS. These findings indicate that the HNF1B variants are directly associated with both diabetes and prostate cancer, that diabetes does not mediate these gene variant prostate cancer relationships, and the relationship between these diseases is not mediated through these gene variants. Prostate 70: 601-607, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Stevens, Victoria L.; Sun, Juzhong; Jacobs, Eric J.; Pate, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30303 USA.
[Ahn, Jiyoung; Moore, Steven C.; Berndt, Sonja I.; Albanes, Demetrius; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Stevens, VL (reprint author), Amer Canc Soc, Dept Epidemiol, 250 Williams St NW, Atlanta, GA 30303 USA.
EM victoria.stevens@cancer.org
RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Hayes, Richard/0000-0002-0918-661X
FU Intramural NIH HHS [ZIA CP010152-11]
NR 31
TC 23
Z9 23
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2010
VL 70
IS 6
BP 601
EP 615
DI 10.1002/pros.21094
PG 15
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 593ST
UT WOS:000277481700004
PM 19998368
ER
PT J
AU Calvo, A
Perez-Stable, C
Segura, V
Catena, R
Guruceaga, E
Nguewa, P
Blanco, D
Parada, L
Reiner, T
Green, JE
AF Calvo, Alfonso
Perez-Stable, Carlos
Segura, Victor
Catena, Raul
Guruceaga, Elizabeth
Nguewa, Paul
Blanco, David
Parada, Luis
Reiner, Teresita
Green, Jeffrey E.
TI Molecular Characterization of the G gamma-Globin-TagTransgenic Mouse
Model of Hormone Refractory Prostate Cancer: Comparison to Human
Prostate Cancer
SO PROSTATE
LA English
DT Article
DE prostate cancer; transgenic mouse; gene expression; microarrays;
stathmin-1
ID GENE-EXPRESSION PROFILES; HUMAN BREAST-CANCER; TRANSGENIC MICE;
NEUROENDOCRINE DIFFERENTIATION; BINDING-PROTEIN; POOR-PROGNOSIS; TUMORS;
PROGRESSION; CARCINOMA; STATHMIN
AB BACKGROUND. Prostate cancer (PrCa) has a high incidence in Western countries and at present, there is no cure for hormone refractory prostate cancer. Transgenic mouse models have proven useful for understanding mechanisms of prostate carcinogenesis. The characterization of genetically modified mouse PrCa models using high-throughput genomic analyses provides important information to guide appropriate experiment applications for such model.
METHODS. We have analyzed the transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T-antigen (G gamma-globin-Tag) transgenic mouse model for PrCa compared to normal mouse prostate tissue. Gene expression patterns found in G gamma-globin-Tag mouse prostate tumors were compared with publicly available human localized and metastatic prostate tumors (GEO accession # GSE3325) through hierarchical cluster analysis, Pearson's rank correlation coefficient, and Self Organizing Feature Maps (SOM) analyses.
RESULTS. G gamma-globin-Tag tumors clustered closely with human metastatic tumors and gene expression patterns had a significant correlation (P < 0.01), unlike human localized primary tumors (P > 0.6). Bioinformatic analyses identified deregulated genetic pathways and networks in G gamma-globin-Tag tumors, which displayed similarities to alterations in human PrCa. Changes in the expression of genes involved in DNA replication and repair (Rb, p53, Myc, PCNA, DNMT3A) and growth factor signaling pathways (TGF beta 2, ERK1/2, NRas, and Notch) are deregulated in the G gamma-globin-Tag tumors, suggesting their key role in the oncogenic process. Identification of an enrichment of putative binding sites for transcription factors revealed eight transcription factors that may be important in G gamma-globin-Tag carcinogenesis, including SP, NF-Y, CREB, Elk, and E2F. Novel genes related to microtubule regulation were also identified in G gamma-globin-Tag tumors as potentially important candidate targets for PrCa. Overexpression of stathmin-1, whose expression was increased in human metastatic prostate tumors, was validated in G gamma-globin-Tag tumors by immunohistochemistry. This protein belongs to the SV40/T-antigen cancer signature identified in previous studies in prostate, breast, and lung cancer mouse models.
CONCLUSIONS. Our results show that the G gamma-globin-Tag model for hormone refractory PrCa shares important features with aggressive, metastatic human PrCa. Given the role of stathmin-1 in the destabilization of microtubles and taxane resistance, the G gamma-globin-Tag model and other SV40/T-antigen driven transgenic models may be useful for testing potential therapies directed at stathmin-1 in human prostate tumors. Prostate 70: 630-645, 2010.Published 2010 Wiley-Liss, Inc.(dagger)
C1 [Calvo, Alfonso; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Calvo, Alfonso; Catena, Raul; Nguewa, Paul; Blanco, David] Univ Navarra, Div Oncol, Dept Histol & Pathol, CIMA, E-31080 Pamplona, Spain.
[Perez-Stable, Carlos; Reiner, Teresita] Univ Miami, Miller Sch Med, Ctr Geriatr Res Educ & Clin, Miami, FL 33136 USA.
[Perez-Stable, Carlos; Reiner, Teresita] Univ Miami, Miller Sch Med, Res Serv, Dept Med, Miami, FL 33136 USA.
[Perez-Stable, Carlos; Reiner, Teresita] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Vet Affairs Med Ctr, Miami, FL 33136 USA.
[Segura, Victor; Guruceaga, Elizabeth] CIMA, Unit Prote Genom & Bioinformat, Pamplona, Spain.
[Parada, Luis] CIC BioGUNE, Derio, Spain.
RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
EM jegreen@nih.gov
RI Segura, Victor/E-4531-2010; Guruceaga, Elizabeth/B-1796-2008
OI Segura, Victor/0000-0002-7740-6290; Guruceaga,
Elizabeth/0000-0003-0547-681X
FU Center for Cancer Research of NIH; ISCIII-RETIC [RD06/0020]; Ministerio
de Educacion y Ciencia [SAF2007-64184]; Spanish Torres-Quevedo
fellowship [PTQ05-01-01084]
FX Grant sponsor: Center for Cancer Research of NIH; Grant sponsor:
ISCIII-RETIC; Grant number: RD06/0020; Grant sponsor: Ministerio de
Educacion y Ciencia; Grant number: SAF2007-64184; Grant sponsor: Spanish
Torres-Quevedo fellowship; Grant number: PTQ05-01-01084.
NR 57
TC 6
Z9 6
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2010
VL 70
IS 6
BP 630
EP 645
DI 10.1002/pros.21097
PG 16
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 593ST
UT WOS:000277481700006
PM 20058236
ER
PT J
AU Lubahn, J
Berndt, SI
Jin, CH
Klim, A
Luly, J
Wu, WS
Isaacs, S
Wiley, K
Isaacs, WB
Suarez, BK
Hayes, RB
Kibel, AS
AF Lubahn, Jessica
Berndt, Sonja I.
Jin, Carol H.
Klim, Aleksandra
Luly, Jason
Wu, William S.
Isaacs, Sarah
Wiley, Kathleen
Isaacs, William B.
Suarez, Brian K.
Hayes, Richard B.
Kibel, Adam S.
TI Association of CASP8 D302H Polymorphism With Reduced Risk of Aggressive
Prostate Carcinoma
SO PROSTATE
LA English
DT Article
DE prostate carcinoma; apoptosis; risk assessment; cancer susceptibility;
metastatic disease
ID GENOME-WIDE ASSOCIATION; COMMON VARIANT; BREAST-CANCER; CELL-DEATH;
CASP8 GENE; SUSCEPTIBILITY; OVERDIAGNOSIS; PROMOTER; DISEASE; 8Q24
AB BACKGROUND. Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele.
METHODS. We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls.
RESULTS. The H allele was associated with a reduced risk of aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54-0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per) (allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per) (allele) = 0.73; 95% CI: 0.50-1.07).
CONCLUSION. These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype. Prostate 70: 646-653, 2010. (C) 2009 Wiley-Liss. Inc.
C1 [Lubahn, Jessica; Klim, Aleksandra; Luly, Jason; Wu, William S.; Kibel, Adam S.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Washington, DC USA.
[Jin, Carol H.; Suarez, Brian K.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Isaacs, Sarah; Wiley, Kathleen; Isaacs, William B.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA.
[Suarez, Brian K.; Kibel, Adam S.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Suarez, Brian K.; Kibel, Adam S.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, Langone Med Ctr, New York, NY 10016 USA.
RP Kibel, AS (reprint author), 4960 Childrens Pl,2nd Floor Wohl Hosp,Box 8242, St Louis, MO 63110 USA.
EM kibela@wustl.edu
OI Hayes, Richard/0000-0002-0918-661X
FU NCI [R01CA112028, R21CA098020]; St. Louis Men's Group Against Cancer;
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH; Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening
Trial
FX This work was supported by NCI (R01CA112028, R21CA098020), the St. Louis
Men's Group Against Cancer, the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH, and Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening
Trial.
NR 31
TC 10
Z9 11
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2010
VL 70
IS 6
BP 646
EP 653
DI 10.1002/pros.21098
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 593ST
UT WOS:000277481700007
PM 20033885
ER
PT J
AU Moon, AF
Mueller, GA
Zhong, XJ
Pedersen, LC
AF Moon, Andrea F.
Mueller, Geoffrey A.
Zhong, Xuejun
Pedersen, Lars C.
TI A synergistic approach to protein crystallization: Combination of a
fixed-arm carrier with surface entropy reduction
SO PROTEIN SCIENCE
LA English
DT Review
DE protein crystallography; surface entropy reduction; carrier-driven
crystallization; MBP; fixed-arm; rescue strategy
ID MALTOSE-BINDING-PROTEIN; CYTOCHROME-C-OXIDASE; ANGSTROM
CRYSTAL-STRUCTURE; IN-SITU PROTEOLYSIS; F-V FRAGMENT; ESCHERICHIA-COLI;
COUPLED-RECEPTOR; DRIVEN CRYSTALLIZATION; FUSION PROTEIN;
PARACOCCUS-DENITRIFICANS
AB Protein crystallographers are often confronted with recalcitrant proteins not readily crystallizable, or which crystallize in problematic forms. A variety of techniques have been used to surmount such obstacles: crystallization using carrier proteins or antibody complexes, chemical modification, surface entropy reduction, proteolytic digestion, and additive screening. Here we present a synergistic approach for successful crystallization of proteins that do not form diffraction quality crystals using conventional methods. This approach combines favorable aspects of carrier-driven crystallization with surface entropy reduction. We have generated a series of maltose binding protein (MBP) fusion constructs containing different surface mutations designed to reduce surface entropy and encourage crystal lattice formation. The MBP advantageously increases protein expression and solubility, and provides a streamlined purification protocol. Using this technique, we have successfully solved the structures of three unrelated proteins that were previously unattainable. This crystallization technique represents a valuable rescue strategy for protein structure solution when conventional methods fail.
C1 [Moon, Andrea F.; Mueller, Geoffrey A.; Zhong, Xuejun; Pedersen, Lars C.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Pedersen, LC (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
EM pederse2@niehs.nih.gov
FU National Institutes of Health (NIH); National Institute of Environmental
Health Sciences (NIEHS)
FX Grant sponsors: Research supported by the Intramural Research Program of
the National Institutes of Health (NIH) and the National Institute of
Environmental Health Sciences (NIEHS).
NR 98
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U1 2
U2 15
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD MAY
PY 2010
VL 19
IS 5
BP 901
EP 913
DI 10.1002/pro.368
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 591DP
UT WOS:000277279500001
PM 20196072
ER
PT J
AU Mashiach, E
Nussinov, R
Wolfson, HJ
AF Mashiach, Efrat
Nussinov, Ruth
Wolfson, Haim J.
TI Fiber Dock: Flexible induced-fit backbone refinement in molecular
docking
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE flexible docking; backbone flexibility; modeling protein-protein
docking; normal modes; prediction of protein-protein interactions
ID PROTEIN-PROTEIN DOCKING; NORMAL-MODE CALCULATIONS; RIGID-BODY DOCKING;
CONFORMATIONAL-CHANGE; LIGAND DOCKING; ROUNDS 3-5; FLEXIBILITY; CAPRI;
BINDING; PREDICTIONS
AB Upon binding, proteins undergo conformational changes. These changes often prevent rigid-body docking methods from predicting the 3D structure of a complex from the unbound conformations of its proteins. Handling protein backbone flexibility is a major challenge for docking methodologies, as backbone flexibility adds a huge number of degrees of freedom to the search space, and therefore considerably increases the running time of docking algorithms. Normal mode analysis permits description of protein flexibility as a linear combination of discrete movements (modes). Low-frequency modes usually describe the large-scale conformational changes of the protein. Therefore, many docking methods model backbone flexibility by using only few modes, which have the lowest frequencies. However, studies show that due to molecular interactions, many proteins also undergo local and small-scale conformational changes, which are described by high-frequency normal modes. Here we present a new method, Fiber Dock, for docking refinement which models backbone flexibility by an unlimited number of normal modes. The method iteratively minimizes the structure of the flexible protein along the most relevant modes. The relevance of a mode is calculated according to the correlation between the chemical forces, applied on each atom, and the translation vector of each atom, according to the normal mode. The results show that the method successfully models backbone movements that occur during molecular interactions and considerably improves the accuracy and the ranking of rigid-docking models of protein protein complexes. A web server for the Fiber Dock method is available at: http://bioinfo3d.cs.tau.ac.il/FiberDock.
C1 [Mashiach, Efrat; Wolfson, Haim J.] Tel Aviv Univ, Blavatnik Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res, Nanobiol Program,NCI Frederick, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
RP Wolfson, HJ (reprint author), Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
EM wolfson@tau.ac.il
RI Wolfson, Haim/A-1837-2011
FU Israel Science Foundation [1403/09]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; NIH [P41 RR-01081]; Tel-Aviv
University; Israel Academy of Sciences and Humanities; NIH, National
Cancer Institute, Center for Cancer Research
FX Grant sponsor: Israel Science Foundation; Grant number: 1403/09; Grant
sponsor: National Cancer Institute, National Institutes of Health; Grant
number: HHSN261200800001E; Grant sponsor: NIH; Grant number: P41
RR-01081; Grant sponsors: Edmond J. Safra Bioinforinatics Program at
Tel-Aviv University, Adams fellowship of the Israel Academy of Sciences
and Humanities, Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 53
TC 81
Z9 83
U1 2
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD MAY 1
PY 2010
VL 78
IS 6
BP 1503
EP 1519
DI 10.1002/prot.22668
PG 17
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 579KS
UT WOS:000276369700013
PM 20077569
ER
PT J
AU Rose, EJ
Ross, TJ
Kurup, PK
Stein, EA
AF Rose, Emma J.
Ross, Thomas J.
Kurup, Pradeep K.
Stein, Elliot A.
TI Nicotine modulation of information processing is not limited to input
(attention) but extends to output (intention)
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Nicotine; Smoking; Intention; Response readiness; Selective attention;
Functional MRI; Information processing
ID LEFT PARIETAL CORTEX; ACOUSTIC STARTLE REFLEX; CIGARETTE-SMOKING;
PREPULSE INHIBITION; SPATIAL ATTENTION; MOTOR ATTENTION; EYE-MOVEMENTS;
VISUOSPATIAL ATTENTION; COGNITIVE PERFORMANCE; NEURAL SYSTEMS
AB Nicotine influences many cognitive processes, especially those requiring high attentional loads, yet the impact of nicotine on all aspects of information processing has not been well delineated.
The aim of the study was to determine the relative behavioral and functional effects of nicotine on dissociable aspects of information processing (i.e., selective attention and motor intention).
Adult smokers (N = 25) and healthy controls (N = 23) performed the intention/attention task (IAT) twice, during functional magnetic resonance imaging. The IAT assesses the relative differences in performance evoked by prime stimuli that provide information regarding either the correct hand with which to respond (i.e., intentional primes) or the likely location of a target stimulus (i.e., attentional primes). Smokers were scanned 2 h after nicotine (21 mg) or placebo patch placement. The order of nicotine and placebo sessions was randomized and counter-balanced. Controls were also scanned twice, with no patch placement in either session.
While drug condition had no significant effect on reaction time, smokers were overall more accurate than controls. Moreover, nicotine significantly increased the response to intentional primes in brain regions known to mediate response readiness, e.g., inferior parietal lobe, supramarginal gyrus, and striatum.
While limited to participant accuracy, these data suggest that the behavioral effects of nicotine in smokers are not only limited to information processing input (i.e., selective attention) but are also generalizable to output functions (i.e., motor intention). Moreover, nicotine's effects on intention appear to be mediated by a facilitation of function in brain regions associated with information processing output.
C1 [Rose, Emma J.; Ross, Thomas J.; Kurup, Pradeep K.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Rose, Emma J.] Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Grp, Dublin, Ireland.
RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 251 Bayview Blvd,Suite 200 NIDA, Baltimore, MD 21224 USA.
EM estein@intra.nida.nih.gov
RI Ross, Thomas/B-7469-2008; Rose, Emma/A-9960-2010
OI Ross, Thomas/0000-0002-7745-3572; Rose, Emma/0000-0001-5365-4794
FU National Institute on Drug Abuse-Intramural Research Program
FX We would like to thank Loretta Spurgeon, Kimberley Modo, NIDA nursing
staff, and Dr. Betty Jo Salmeron for their contributions in running this
study and Dr. Frank Wolkenberg for experiment design assistance. This
study was supported by the National Institute on Drug Abuse-Intramural
Research Program.
NR 88
TC 11
Z9 11
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2010
VL 209
IS 4
BP 291
EP 302
DI 10.1007/s00213-010-1788-9
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 584BA
UT WOS:000276723800002
PM 20309531
ER
PT J
AU von Leupoldt, A
Vovk, A
Bradley, MM
Keil, A
Lang, PJ
Davenport, PW
AF von Leupoldt, Andreas
Vovk, Andrea
Bradley, Margaret M.
Keil, Andreas
Lang, Peter J.
Davenport, Paul W.
TI The impact of emotion on respiratory-related evoked potentials
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Dyspnea; EEG; Emotion; Perception; Respiration; Respiratory-related
evoked potential
ID OBSTRUCTIVE PULMONARY-DISEASE; INSPIRATORY RESISTIVE LOADS;
EVENT-RELATED POTENTIALS; NEAR-FATAL ASTHMA; SYMPTOM PERCEPTION;
PSYCHOLOGICAL-ASPECTS; AFFECTIVE PICTURES; PERCEIVED DYSPNEA; AIRWAY
OCCLUSION; PEDIATRIC ASTHMA
AB Emotion influences the perception of respiratory sensations, although the specific mechanism underlying this modulation is not yet clear. We examined the impact of viewing pleasant, neutral, and unpleasant affective pictures on the respiratory-related evoked potential (RREP) elicited by a short inspiratory occlusion in healthy volunteers. Reduced P3 amplitude of the RREP was found for respiratory probes presented when viewing pleasant or unpleasant series, when compared to those presented during the neutral series. Earlier RREP components, such as Nf, P1, N1, and P2, showed no modulation by emotion. The results suggest that emotion impacts the perception of respiratory sensations by reducing the attentional resources available for processing afferent respiratory sensory signals.
C1 [von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, D-20146 Hamburg, Germany.
[von Leupoldt, Andreas; Vovk, Andrea; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA.
[von Leupoldt, Andreas] Univ Med Ctr, Dept Syst Neurosci, Hamburg, Germany.
[von Leupoldt, Andreas; Bradley, Margaret M.; Keil, Andreas; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA.
RP von Leupoldt, A (reprint author), Univ Hamburg, Dept Psychol, Von Melle Pk 5, D-20146 Hamburg, Germany.
EM andreas.vonleupoldt@uni-hamburg.de
RI Keil, Andreas/F-9427-2011
OI Keil, Andreas/0000-0002-4064-1924
FU National Institute of Mental Health [P50 MH 72850]; German Research
Society (Deutsche Forschungsgemeinschaft, DFG) [1843/9-1]
FX The authors wish to thank Bethany Wangelin, Marie Karlsson, Vincent
Costa, Joshua R. Shumen, Mark Hotchkiss, Nicole Wedell, Katja Wedell,
and A. Daniel Martin for assistance and support. This study was
supported in part by a grant from the National Institute of Mental
Health (P50 MH 72850) to Peter J. Lang, and by a stipend
(Heisenberg-Stipendium, DFG LE 1843/9-1) from the German Research
Society (Deutsche Forschungsgemeinschaft, DFG) to Andreas von Leupoldt.
NR 72
TC 19
Z9 19
U1 0
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD MAY
PY 2010
VL 47
IS 3
BP 579
EP 586
DI 10.1111/j.1469-8986.2009.00956.x
PG 8
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 579VY
UT WOS:000276406100018
PM 20070570
ER
PT J
AU Reeve, BB
AF Reeve, Bryce B.
TI An opportunity to refine our understanding of "response shift" and to
educate researchers on designing quality research studies: response to
Ubel, Peeters, and Smith
SO QUALITY OF LIFE RESEARCH
LA English
DT Editorial Material
DE Response shift; Theory; Adaptation; Methodology
ID TRUE CHANGE
AB There is no advantage at this time to abandon the term "response shift" as suggested by Ubel et al. (Qual Life Res, 2010). The term is well known in the research field and has impacted the way we think about measuring quality of life (QOL) longitudinally. However, Ubel et al. (Qual Life Res, 2010) have provided the incentive to start an open dialogue on the subject with opportunities to refine the language of response shift and educate researchers. In this article, we identify opportunities in designing research studies to minimize or account for response shifts by considering the (1) selection of QOL concepts to measure, (2) questionnaires used to assess the QOL concepts, (3) design of the research study, (4) target population, and (5) analyses and reporting of results. Careful consideration of each of these issues will help us identify new methodologies and improved study designs that will move the QOL research field forward.
C1 Natl Canc Inst, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Reeve, BB (reprint author), Natl Canc Inst, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN 4088,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA.
EM reeveb@mail.nih.gov
NR 13
TC 7
Z9 7
U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD MAY
PY 2010
VL 19
IS 4
BP 473
EP 475
DI 10.1007/s11136-010-9612-x
PG 3
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 581HN
UT WOS:000276512700003
PM 20336490
ER
PT J
AU Jacob, P
Ron, E
AF Jacob, P.
Ron, E.
TI Late health effects of ionizing radiation: bridging the experimental and
epidemiological divide
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Editorial Material
C1 [Jacob, P.] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany.
[Ron, E.] NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Jacob, P (reprint author), Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany.
EM jacob@helmholtz-muenchen.de; eron@exchange.nih.gov
NR 10
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAY
PY 2010
VL 49
IS 2
BP 109
EP 110
DI 10.1007/s00411-010-0273-5
PG 2
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 584IU
UT WOS:000276745900001
PM 20213137
ER
PT J
AU Bolch, W
Lee, C
Wayson, M
Johnson, P
AF Bolch, Wesley
Lee, Choonsik
Wayson, Michael
Johnson, Perry
TI Hybrid computational phantoms for medical dose reconstruction
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Review
ID ORGAN DOSIMETRY; PROTON THERAPY; HUMAN ANATOMY; PATIENT SIZE; ADULT;
MODELS; MORPHOMETRY; POPULATION; PROTECTION; SCHEMA
AB As outlined in NCRP Report No. 160 of the US National Council on Radiation Protection and Measurements (NCRP), the average value of the effective dose to exposed individuals in the United States has increased by a factor of 1.7 over the time period 1982-2006, with the contribution of medical exposures correspondingly increasing by a factor of 5.7. At present, medical contributors to effective dose include computed tomography (50% of total medical exposure), nuclear medicine (25%), interventional fluoroscopy (15%), and conventional radiography and diagnostic fluoroscopy (10%). An increased awareness of medical exposures has led to a gradual shift in the focus of radiation epidemiological studies from traditional occupational and environmental exposures to those focusing on cohorts of medical patients exposed to both diagnostic and therapeutic sources. The assignment of organ doses to patients in either a retrospective or a prospective study has increasingly relied on the use of computational anatomic phantoms. In this paper, we review the various methods and approaches used to construct patient models to include anthropometric databases, cadaver imaging, prospective volunteer imaging studies, and retrospective image reviews. Phantom format types-stylized, voxel, and hybrid-as well as phantom morphometric categories-reference, patient-dependent, and patient-specific-are next defined and discussed. Specific emphasis is given to hybrid phantoms-those defined through the use of combinations of polygon mesh and non-uniform rational B-spline (NURBS) surfaces. The concept of a patient-dependent phantom is reviewed, in which phantoms of non-50th percentile heights and weights are designed from population-based morphometric databases and provided as a larger library of phantoms for patient matching and lookup of refined values of organ dose coefficients and/or radionuclide S values. We close with two brief examples of the use of hybrid phantoms in medical dose reconstruction-diagnostic nuclear medicine for pediatric subjects and interventional fluoroscopy for adult patients.
C1 [Bolch, Wesley; Wayson, Michael; Johnson, Perry] Univ Florida, Dept Nucl & Radiol Engn, Adv Lab Radiat Dosimetry Studies ALRADS, Gainesville, FL 32611 USA.
[Bolch, Wesley] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Bolch, W (reprint author), Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
EM wbolch@ufl.edu
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
FU Intramural NIH HHS [Z01 CP010131-12, ZIA CP010131-14]
NR 45
TC 20
Z9 20
U1 4
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAY
PY 2010
VL 49
IS 2
BP 155
EP 168
DI 10.1007/s00411-009-0260-x
PG 14
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 584IU
UT WOS:000276745900006
PM 20039051
ER
PT J
AU Krestinina, L
Preston, DL
Davis, FG
Epifanova, S
Ostroumova, E
Ron, E
Akleyev, A
AF Krestinina, Lyudmila
Preston, Dale L.
Davis, Faith G.
Epifanova, Svetlana
Ostroumova, Evgenia
Ron, Elaine
Akleyev, Alexander
TI Leukemia incidence among people exposed to chronic radiation from the
contaminated Techa River, 1953-2005
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Article
ID CANCER-MORTALITY RISK; ATOMIC-BOMB SURVIVORS; COHORT; RECONSTRUCTION;
POPULATION; DOSIMETRY; WORKERS; SYSTEM
AB Beginning in 1950, people living on the banks of the Techa River received chronic low-dose-rate internal and external radiation exposures as a result of releases from the Mayak nuclear weapons plutonium production facility in the Southern Urals region of the Russian Federation. The Techa River cohort includes about 30,000 people who resided in riverside villages sometime between 1950 and 1960. Cumulative red bone marrow doses range up to 2 Gy with a mean of 0.3 Gy and a median of 0.2 Gy. Between 1953 and 2005, 93 first primary cases of leukemia, including 23 cases of chronic lymphatic leukemia (CLL), were ascertained among the cohort members. A significant linear dose-response relationship was seen for leukemias other than CLL (P < 0.001), but not for CLL. The estimated excess relative risk per Gy is 4.9 (95% confidence interval (CI): 1.6; 14.3) for leukemias other than CLL and less than 0 (95% upper bound 1.4) for CLL.
C1 [Krestinina, Lyudmila; Epifanova, Svetlana; Ostroumova, Evgenia; Akleyev, Alexander] Urals Res Ctr Radiat Med, Chelyabinsk 454076, Russia.
[Preston, Dale L.] Hirosoft Int Corp, Eureka, CA 95501 USA.
[Davis, Faith G.] Univ Illinois, Sch Publ Hlth, Chicago, IL 60612 USA.
[Ron, Elaine] NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Krestinina, L (reprint author), Urals Res Ctr Radiat Med, 68-A,Vorovsky St, Chelyabinsk 454076, Russia.
EM ludmila@urcrm.chel.su
RI Akleyev, Alexander/Q-1891-2015
OI Akleyev, Alexander/0000-0003-2583-5808
FU U.S. Department of Energy, Office of Health Studies; U.S. National
Institutes of Health; National Cancer Institute; Russian Ministry of
Health
FX This work (epidemiological and dosimetry investigations) has been
supported by the U.S. Department of Energy, Office of Health Studies and
by the U.S. National Institutes of Health, National Cancer Institute.
The Federal Department of the Russian Ministry of Health has also
provided support for all aspects of this study. Many people have made
important contributions to this study. We acknowledge the contributions
of Marina Degteva, Nikolai Startsev, Catherine Zhidkova, and physicians
of URCRM clinical Department.
NR 16
TC 20
Z9 24
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAY
PY 2010
VL 49
IS 2
BP 195
EP 201
DI 10.1007/s00411-009-0257-5
PG 7
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 584IU
UT WOS:000276745900010
PM 20012750
ER
PT J
AU Gilbert, ES
Huang, L
Bouville, A
Berg, CD
Ron, E
AF Gilbert, Ethel S.
Huang, Lan
Bouville, Andre
Berg, Christine D.
Ron, Elaine
TI Thyroid Cancer Rates and I-131 Doses from Nevada Atmospheric Nuclear
Bomb Tests: An Update
SO RADIATION RESEARCH
LA English
DT Article
ID INCREASING INCIDENCE; CHERNOBYL ACCIDENT; FALLOUT; RADIATION; PAPILLARY;
EXPOSURE; DISEASE; TRENDS; SITE
AB Exposure to radioactive iodine (I-131) from atmospheric nuclear tests conducted in Nevada in the 1950s may have increased thyroid cancer risks. To investigate the long-term effects of this exposure, we analyzed data on thyroid cancer incidence (18,545 cases) from eight Surveillance, Epidemiology, and End Results (SEER) tumor registries for the period 1973-2004. Excess relative risks (ERR) per gray (Gy) for exposure received before age 15 were estimated by relating age-, birth year-, sex- and county-specific thyroid cancer rates to estimates of cumulative dose to the thyroid that take age into account. The estimated ERR per Gy for dose received before 1 year of age was 1.8 [95% confidence interval (Cl), 0.5-3.2]. There was no evidence that this estimate declined with follow-up time or that risk increased with dose received at ages 1-15. These results confirm earlier findings based on less extensive data for the period 1973-1994. The lack of a dose response for those exposed at ages 1-15 is inconsistent with studies of children exposed to external radiation or I-131 from the Chernobyl accident, and results need to be interpreted in light of limitations and biases inherent in ecological studies, including the error in doses and case ascertainment resulting from migration. Nevertheless, the study adds support for an increased risk of thyroid cancer due to fallout, although the data are inadequate to quantify it. (C) 2010 by Radiation Research Society
C1 [Gilbert, Ethel S.; Bouville, Andre; Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Huang, Lan] Fed Drug Adm, Div Biometr 5, Off Biostat, Ctr Drug Evaluat & Res, Bethesda, MD USA.
[Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Huang, Lan] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Gilbert, ES (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MS 7238,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM gilberte@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010131-17]
NR 23
TC 6
Z9 6
U1 0
U2 2
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 MAY
PY 2010
VL 173
IS 5
BP 659
EP 664
DI 10.1667/RR2057.1
PG 6
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 595QS
UT WOS:000277628000010
PM 20426666
ER
PT J
AU Collen, J
Greenburg, D
Holley, A
King, C
Roop, S
Hnatiuk, O
AF Collen, Jacob
Greenburg, David
Holley, Aaron
King, Christopher
Roop, Stuart
Hnatiuk, Oleh
TI Racial discordance in spirometry comparing four commonly used reference
equations to the National Health and Nutrition Examination Study III
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Spirometry; African-American; Discordance; Pulmonary function test
ID FORCED EXPIRATORY VOLUME; REFERENCE VALUES; LUNG-FUNCTION; VITAL
CAPACITY; UNITED-STATES; AFRICAN; MANAGEMENT; ADULTS
AB Diagnosing lung function abnormalities requires application of the appropriate reference equation for a given patient population. Current guidelines recommend the National Health and Examination Study III data set for evaluating patients in the United States. In Caucasian patients, relying on older reference equations, as opposed to those derived from the NHANES Ill data set, will often result in a different interpretation of a patient's spirometry. The present study assessed whether similar discordance would occur in African-American patients.
A cross-sectional analysis of African-American patients undergoing spirometry testing at our hospital was performed. Patients were classified as normal, restricted, obstructed or mixed based upon the ATS/ERS guidelines, using Crapo, Knudson, Morris, Glindmeyer, and NHANES III prediction equations. Differences in classification were evaluated.
4463 subjects were identified, with a mean age of 49.6. Discordance in interpretation was most common when results from prediction equations by Morris, Knudson, and Glindmeyer were compared to NHANES III (24.6%, 26.4%, and 20.1%, respectively). Discordance was less common when comparing Crapo to NHANES III (12.8%). There was a tendency for Knudson, Morris and Glindmeyer to under classify restriction, and for Crapo, Morris, and Glindmeyer to over classify obstruction.
There is significant discordance in interpretation when spirometry for African-American patients is referenced to equations published by Crapo, Morris, Knudson, and Glindmeyer, compared to NHANES III. Published by Elsevier Ltd.
C1 [Collen, Jacob; Holley, Aaron; King, Christopher; Roop, Stuart] USA, Walter Reed Army Med Ctr, Washington, DC 20310 USA.
[Greenburg, David] USA, Madigan Army Med Ctr, Tacoma, WA USA.
[Hnatiuk, Oleh] NIH, Bethesda, MD 20892 USA.
RP Collen, J (reprint author), USA, Walter Reed Army Med Ctr, Washington, DC 20310 USA.
EM jacob.collen@amedd.army.mil; dgreenburg@usuhs.mil;
aaron.holley@amedd.army.mil; christopher.king@amedd.army.mil;
stuart.roop@amedd.army.mil; hnatiuko@nhlbi.nih.gov
NR 31
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD MAY
PY 2010
VL 104
IS 5
BP 705
EP 711
DI 10.1016/j.rmed.2009.11.001
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 604MD
UT WOS:000278282200012
PM 19931442
ER
PT J
AU Gottschalk, P
Huynh, M
AF Gottschalk, Peter
Huynh, Minh
TI ARE EARNINGS INEQUALITY AND MOBILITY OVERSTATED? THE IMPACT OF
NONCLASSICAL MEASUREMENT ERROR
SO REVIEW OF ECONOMICS AND STATISTICS
LA English
DT Article
ID EXTENT
AB Measures of inequality and mobility based on self-reported earnings reflect attributes of both the joint distribution of earnings across time and the joint distribution of measurement error and earnings. While classical measurement error would increase measures of inequality and mobility, there is substantial evidence that measurement error in earnings is not classical. In this paper, we present the analytical links between nonclassical measurement error and some summary measures of inequality and mobility. The empirical importance of nonclassical measurement error is explored using the Survey of Income and Program Participation (SIPP) matched to tax records. We find that the effects of nonclassical measurement error are large. However, these nonclassical effects are largely offsetting when estimating mobility, as measured by the intertemporal correlation in earnings. As a result, SIPP estimates of the correlation are similar to estimates based on tax records, though SIPP estimates of inequality are smaller than estimates based on tax records.
C1 [Gottschalk, Peter] Boston Coll, Chestnut Hill, MA 02167 USA.
[Huynh, Minh] NIH, Bethesda, MD 20892 USA.
RP Gottschalk, P (reprint author), Boston Coll, Chestnut Hill, MA 02167 USA.
NR 19
TC 24
Z9 24
U1 0
U2 7
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0034-6535
J9 REV ECON STAT
JI Rev. Econ. Stat.
PD MAY
PY 2010
VL 92
IS 2
BP 302
EP 315
DI 10.1162/rest.2010.11232
PG 14
WC Economics; Social Sciences, Mathematical Methods
SC Business & Economics; Mathematical Methods In Social Sciences
GA 589OL
UT WOS:000277160600006
ER
PT J
AU Perez, P
Aguilera, S
Olea, N
Alliende, C
Molina, C
Brito, M
Barrera, MJ
Leyton, C
Rowzee, A
Gonzalez, MJ
AF Perez, Paola
Aguilera, Sergio
Olea, Nancy
Alliende, Cecilia
Molina, Claudio
Brito, Monica
Barrera, Maria-Jose
Leyton, Cecilia
Rowzee, Anne
Gonzalez, Maria-Julieta
TI Aberrant localization of ezrin correlates with salivary acini
disorganization in Sjogren's Syndrome
SO RHEUMATOLOGY
LA English
DT Article
DE Ezrin; Cytoskeleton; Apical pole; Microvilli; Cell polarity;
Hyposecretion; Salivary gland; Sjogren's syndrome
ID FUNCTIONALLY DISTINCT POOLS; GASTRIC PARIETAL-CELLS; EPITHELIAL-CELLS;
ERM PROTEINS; ANTIMUSCARINIC ANTIBODIES; ALTERED EXPRESSION;
ENDOTHELIAL-CELLS; SECRETORY-CELLS; BASAL LAMINA; TNF-ALPHA
AB Objectives. To analyse whether the alterations in the structure and organization of microvilli in salivary acinar cells from SS patients are linked to changes in the expression and/or cellular localization of ezrin.
Methods. Salivary gland (SG) acini from controls and SS patients were used to evaluate ezrin expression by western blot and localization of total and activated (phospho-Thr567) ezrin by IF and EM.
Results. In acini from control labial SGs, ezrin was located predominantly at the apical pole and to a lesser extent at the basal region of these cells. Conversely, in acini extracts from SS patients, ezrin showed significantly elevated levels, which were accompanied with localization mostly at the basal region. Moreover, F-actin maintained its distribution in both the apical region and basolateral cortex; however, it was also observed in the acinar cytoplasm. Phospho-ezrin (active form) was located exclusively at the apical pole of acinar cells from control subjects and abundantly located at the basal cytoplasm in SS samples. These results were confirmed by immunogold studies.
Conclusions. The decrease of ezrin and phospho-ezrin at the apical pole and the cytoplasmic redistribution of F-actin suggest an altered interaction between the F-actin-cytoskeleton and plasma membrane in SS patient acini, which may explain the microvilli disorganization. These alterations could eventually contribute to SG hyposecretion in SS patients.
C1 [Gonzalez, Maria-Julieta] Univ Chile, Fac Med, Inst Biomed Sci, Program Mol & Cell Biol,ICBM, Santiago 7, Chile.
[Aguilera, Sergio] Mayor Univ, INDISA Clin, Santiago, Chile.
[Rowzee, Anne] NIDCR, NIH, Bethesda, MD USA.
RP Gonzalez, MJ (reprint author), Univ Chile, Fac Med, Inst Biomed Sci, Program Mol & Cell Biol,ICBM, Casilla 70061, Santiago 7, Chile.
EM jgonzale@med.uchile.cl
FU FONDECYT-CHILE [1080006, 1050192]; Conicyt; Mecesup-Postgrade University
of Chile [99-03]
FX Supported by grants (to M.-J.G., S.A. and C.M.) FONDECYT-CHILE 1080006,
1050192. P. P. and M. B. were supported by PhD fellowships granted by
Conicyt, Mecesup-Postgrade University of Chile 99-03.
NR 39
TC 10
Z9 10
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD MAY
PY 2010
VL 49
IS 5
BP 915
EP 923
DI 10.1093/rheumatology/keq033
PG 9
WC Rheumatology
SC Rheumatology
GA 584FM
UT WOS:000276736400012
PM 20185532
ER
PT J
AU Chen, ZG
Eggerman, TL
Bocharov, AV
Baranova, IN
Vishnyakova, TG
Csako, G
Patterson, AP
AF Chen, Zhigang
Eggerman, Thomas L.
Bocharov, Alexander V.
Baranova, Irina N.
Vishnyakova, Tatyana G.
Csako, Gyorgy
Patterson, Amy P.
TI Hypermutation induced by APOBEC-1 overexpression can be eliminated
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE apolipoprotein; editing; hyperediting; APOBEC-1; ACF; hypermutation
ID B MESSENGER-RNA; LOW-DENSITY LIPOPROTEINS; EDITING ENZYME APOBEC1;
APOLIPOPROTEIN-B; MOORING SEQUENCE; CATALYTIC SUBUNIT; EXPRESSION;
PROTEIN; MICE; BINDING
AB APOBEC-1 overexpression in liver has been shown to effectively reduce apoB-100 levels. However, nonspecific hypermutation and liver tumor formation potentially related to hypermutation in transgenic animals compromise its potential use for gene therapy. In studying apoB mRNA editing regulation, we found that the core editing auxiliary factor ACF dose-dependently increases APOBEC-1 nonspecific hypermutation and specific editing with variable site sensitivity. Overexpression of APOBEC-1 together with ACF in human hepatic HepG2 cells hypermutated apoB mRNAs 20%-65% at sites 6639, 6648, 6655, 6762, 6802, and 6845, in addition to the normal 90% editing at 6666. The hypermutation activity of APOBEC-1 was decreased to background levels by a single point APOBEC-1 mutation of P29F or E181Q, while 50% of wild-type control editing at the normal site was retained. The hypermutations on both apoB and novel APOBEC-1 target 1 ( NAT1) mRNA were also decreased to background levels with P29F and E181Q mutants in rat liver primary culture cells. The loss of hypermutation with the mutants was associated with significantly decreased APOBEC-1/ACF interaction. These data suggest that nonspecific hypermutation induced by overexpressing APOBEC-1 can be virtually eliminated by site-specific mutation, while maintaining specific editing activity at the normal site, reopening the potential use of APOBEC-1 gene therapy for hyperlipidemia.
C1 [Patterson, Amy P.] NIH, Off Sci Policy, Off Director, Bethesda, MD 20892 USA.
[Eggerman, Thomas L.] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Chen, Zhigang; Eggerman, Thomas L.; Bocharov, Alexander V.; Baranova, Irina N.; Vishnyakova, Tatyana G.; Csako, Gyorgy; Patterson, Amy P.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Patterson, AP (reprint author), NIH, Off Sci Policy, Off Director, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA.
EM pattersa@od.nih.gov
FU National Institute of Health; National Institute of Allergy and
Infectious Diseases (NIAID); National Heart, Lung, Blood Institute
(NHLBI); National Institute of Diabetes and Digestive and Kidney
Diseases
FX This research was supported by the Intramural Research Programs of the
National Institute of Health including the Clinic Center ( CC), The
National Institute of Allergy and Infectious Diseases (NIAID), The
National Heart, Lung, Blood Institute (NHLBI), and National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 33
TC 6
Z9 8
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD MAY
PY 2010
VL 16
IS 5
BP 1040
EP 1052
DI 10.1261/rna.1863010
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 585NN
UT WOS:000276832600016
PM 20348446
ER
PT J
AU Strohmaier, J
Frank, J
Wendland, JR
Schumacher, J
Abou Jamra, R
Treutlein, J
Nieratschker, V
Breuer, R
Mattheisen, M
Herms, S
Muhleisen, TW
Maier, W
Nothen, MM
Cichon, S
Rietschel, M
Schulze, TG
AF Strohmaier, Jana
Frank, Josef
Wendland, Jens R.
Schumacher, Johannes
Abou Jamra, Rami
Treutlein, Jens
Nieratschker, Vanessa
Breuer, Rene
Mattheisen, Manuel
Herms, Stefan
Muehleisen, Thomas W.
Maier, Wolfgang
Noethen, Markus M.
Cichon, Sven
Rietschel, Marcella
Schulze, Thomas G.
TI A reappraisal of the association between Dysbindin (DTNBP1) and
schizophrenia in a large combined case-control and family-based sample
of German ancestry
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Polymorphism; COMT; Epistasis; Endophenotype; Cognitive function
ID CATECHOL-O-METHYLTRANSFERASE; GENE DTNBP1; RISK HAPLOTYPE; 6P22.3 GENE;
POPULATION; COGNITION; EXPRESSION; EPISTASIS; LINKAGE; GENOME
AB Background: Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity.
Method: Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219: TMT-B: n = 247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT.
Results: No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons.
Conclusions: Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions. Published by Elsevier B.V.
C1 [Wendland, Jens R.; Schumacher, Johannes; Schulze, Thomas G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Strohmaier, Jana; Frank, Josef; Treutlein, Jens; Nieratschker, Vanessa; Breuer, Rene; Rietschel, Marcella; Schulze, Thomas G.] Cent Inst Mental Hlth, Div Genet Epidemiol, D-6800 Mannheim, Germany.
[Schumacher, Johannes; Mattheisen, Manuel; Herms, Stefan; Muehleisen, Thomas W.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Abou Jamra, Rami; Mattheisen, Manuel; Herms, Stefan; Muehleisen, Thomas W.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Maier, Wolfgang] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany.
RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, 35 Convent Dr,Bldg 35,Rm 1A205,MSC 3719, Bethesda, MD 20892 USA.
EM schulzet@mail.nih.gov
RI Wendland, Jens/A-1809-2012; Schulze, Thomas/H-2157-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra,
Rami/I-4805-2015; Mattheisen, Manuel/B-4949-2012; Schumacher,
Johannes/F-4970-2015; Herms, Stefan/J-1949-2014
OI Cichon, Sven/0000-0002-9475-086X; Nothen, Markus/0000-0002-8770-2464;
Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399;
Mattheisen, Manuel/0000-0002-8442-493X; Schumacher,
Johannes/0000-0001-9217-6457; Herms, Stefan/0000-0002-2786-8200
FU National Genome Research Network (NGFN) of the German Federal Ministry
of Education and Research (BMBF); National Institute of Mental Health
(NIMH); NARSAD
FX This work was supported by the National Genome Research Network (NGFN)
of the German Federal Ministry of Education and Research (BMBF) and the
National Institute of Mental Health (NIMH). TGS received support from
NARSAD (Young Investigator Award 2007). MMN and SC received support from
the Alfried Krupp von Bohlen und Halbach-Stiftung. Ioline Henter
provided outstanding editorial assistance.
NR 57
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAY
PY 2010
VL 118
IS 1-3
BP 98
EP 105
DI 10.1016/j.schres.2009.12.025
PG 8
WC Psychiatry
SC Psychiatry
GA 603NE
UT WOS:000278214500015
PM 20083391
ER
PT J
AU Catherino, WH
AF Catherino, William H.
TI Insight and Advances in Uterine Leiomyomas PREFACE
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Editorial Material
C1 [Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM wcatherino@usuhs.mil
NR 0
TC 1
Z9 1
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD MAY
PY 2010
VL 28
IS 3
BP 166
EP 167
DI 10.1055/s-0030-1251474
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 587FW
UT WOS:000276976400002
PM 20414840
ER
PT J
AU Malik, M
Norian, J
McCarthy-Keith, D
Britten, J
Catherino, WH
AF Malik, Minnie
Norian, John
McCarthy-Keith, Desiree
Britten, Joy
Catherino, William H.
TI Why Leiomyomas Are Called Fibroids: The Central Role of Extracellular
Matrix in Symptomatic Women
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Uterine leiomyoma; extracellular matrix; collagen; proteoglycan;
transforming growth factor (TGF)
ID GROWTH-FACTOR-BETA; PROGESTERONE-RECEPTOR MODULATOR;
GONADOTROPIN-RELEASING-HORMONE; SMOOTH-MUSCLE-CELLS; UTERINE LEIOMYOMA;
TGF-BETA; NORMAL MYOMETRIUM; CONTROLLED-TRIAL; DOUBLE-BLIND;
METALLOPROTEINASE INDUCER
AB Uterine leiomyomas are highly prevalent and symptomatic tumors of women in their reproductive years. The morbidity caused by these tumors is directly related to increasing size. Leiomyoma cells do not rapidly proliferate; instead, the tumors grow primarily due to excessive production of disorganized extracellular matrix (ECM). The aberrant ECM results from excessive production of collagen subtypes and proteoglycans, increased profibrotic cytokines including transforming growth factors beta 1 and beta 3, and decreased or disrupted matrix metalloproteinases. These alterations result in the development of an ECM that is exceptionally stable. As a result, therapeutic interventions must redirect leiomyoma cells toward extracellular matrix dissolution, rather than solely inhibiting cell proliferation. Gonadotropin-releasing hormone analogues and selective progesterone receptor modulators with demonstrated clinical efficacy provide such a change in abnormal extracellular matrix formation by leiomyoma cells, inhibiting and reversing the fibrotic process. Novel therapies using pathways distinct from gonadal hormones, including antifibrotics, retinoic acid, peroxisome-proliferator-activated receptor gamma ligands, and curcumin, provide promise for a future with improved therapeutic options for women suffering from uterine leiomyomas.
C1 [Malik, Minnie; Norian, John; McCarthy-Keith, Desiree; Britten, Joy; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Norian, John; McCarthy-Keith, Desiree; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM wcatherino@usuhs.mil
OI Malik, Minnie/0000-0003-1129-6575
FU EMD Serono; National Institute of Child Health and Human Development
(NICHD), National Institutes of Health (NIH)
FX The studies presented were supported by a generous research grant by EMD
Serono and by the intramural branch of the Program in Reproductive and
Adult Endocrinology, National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH). Disclosure:
The opinions or assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the
views of the Department of Health and Human Services, the Department of
Agriculture, or the Department of Defense.
NR 68
TC 43
Z9 45
U1 0
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD MAY
PY 2010
VL 28
IS 3
BP 168
EP 178
DI 10.1055/s-0030-1251475
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 587FW
UT WOS:000276976400003
PM 20414841
ER
PT J
AU Laughlin, SK
Schroeder, JC
Baird, DD
AF Laughlin, Shannon K.
Schroeder, Jane C.
Baird, Donna Day
TI New Directions in the Epidemiology of Uterine Fibroids
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Uterine leiomyoma; epidemiology; reproductive tract infection; sexually
transmitted disease; metabolic factors; diet; environment
ID UNITED-STATES; RISK-FACTORS; PREMENOPAUSAL WOMEN; DEVELOPMENTAL
EXPOSURE; DIETHYLSTILBESTROL DES; REPRODUCTIVE FACTORS; ENDOMETRIAL
CANCER; GENE-EXPRESSION; BREAST-CANCER; BODY-SIZE
AB Although uterine leiomyomata (fibroids) have been the leading indication for hysterectomy in the United States for decades, the epidemiological data on fibroid prevalence and risk factors are limited. Given the hormonal dependence of fibroids, most earlier studies focused on reproductive or hormonal factors. Recent analyses have extended that focus to other areas. We present previously unpublished data on the association between reproductive tract infections and fibroids that highlight the need for more detailed studies. Our review suggests that metabolic, dietary, stress, and environmental factors may also play a role in fibroid development.
C1 [Baird, Donna Day] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Laughlin, Shannon K.] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USA.
[Schroeder, Jane C.] NIEHS, NIH, Morrisville, NC USA.
RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, NIH, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU Intramural NIH HHS [ZIA ES049013-18]
NR 88
TC 74
Z9 79
U1 1
U2 25
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD MAY
PY 2010
VL 28
IS 3
BP 203
EP 216
DI 10.1055/s-0030-1251477
PG 14
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 587FW
UT WOS:000276976400005
PM 20414843
ER
PT J
AU Yu, LD
Moore, AB
Dixon, D
AF Yu, Linda
Moore, Alicia B.
Dixon, Darlene
TI Receptor Tyrosine Kinases and Their Hormonal Regulation in Uterine
Leiomyoma
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Receptor tyrosine kinases (RTKs); hormonal regulation; uterus;
leiomyoma; growth factors; fibroids
ID GROWTH-FACTOR-I; SMOOTH-MUSCLE-CELLS; ESTROGEN-RECEPTOR;
GENE-EXPRESSION; IGF-I; MATCHED MYOMETRIUM; PROTEIN-KINASE;
CANCER-THERAPY; PROLIFERATION; PROGESTERONE
AB Uterine leiomyomas (fibroids, myomas) are benign tumors that develop from smooth muscle cells. Although the most common gynecologic tumor in premenopausal women, there is still little known of the etiology, the genetics and basic/molecular biology, or the influence of the environment on the development and growth of these tumors. The fact that fibroids occur during the reproductive years and regress after menopause indicates a growth dependent on ovarian hormones. Studies have supported a role of estrogen and progesterone in leiomyoma growth possibly through regulating growth factors and their signaling pathways. Activation of steroid hormone receptors can have a myriad of effects and include upregulation of growth factors and receptor tyrosine kinases (RTKs), which through downstream effector proteins such as mitogen-activated protein kinase p44/42, can mediate transcription, translation, and cell proliferation. Due to their hormonal dependency, fibroids may also be targeted by environmental chemicals whose biological effects are mediated through the estrogen and/or progesterone receptors. This review focuses on the role of growth factors and their receptors (RTKs) in uterine leiomyoma growth and their regulation by ovarian hormones. It also presents data on specific signaling pathways activated in uterine leiomyomas and the "cross talk'' between the estrogen receptor a and RTK signaling pathways.
C1 [Yu, Linda; Moore, Alicia B.; Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Dixon, D (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,Dept Hlth & Human Serv, 111 TW Alexander Dr, POB 12233,Bldg 101 Rm C254A, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
NR 49
TC 10
Z9 12
U1 0
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD MAY
PY 2010
VL 28
IS 3
BP 249
EP 258
DI 10.1055/s-0030-1251482
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 587FW
UT WOS:000276976400010
PM 20414848
ER
PT J
AU Vorspan, F
Guillem, E
Bloch, V
Bellais, L
Sicot, R
Noble, F
Lepine, JP
Gorelick, DA
AF Vorspan, Florence
Guillem, Eric
Bloch, Vanessa
Bellais, Laetitia
Sicot, Romain
Noble, Florence
Lepine, Jean-Pierre
Gorelick, David A.
TI Self-reported sleep disturbances during cannabis withdrawal in
cannabis-dependent outpatients with and without opioid dependence
SO SLEEP MEDICINE
LA English
DT Letter
ID USERS
C1 [Vorspan, Florence; Guillem, Eric; Bloch, Vanessa; Bellais, Laetitia; Sicot, Romain; Lepine, Jean-Pierre] Hop Fernand Widal, AP HP, Psychiat Serv, F-75475 Paris 10, France.
[Gorelick, David A.] NIDA Intramural Res Program, Baltimore, MD 21224 USA.
[Vorspan, Florence; Guillem, Eric; Bloch, Vanessa; Bellais, Laetitia; Noble, Florence; Lepine, Jean-Pierre] Univ Paris 05, CNRS, UMR 7157, INSERM,U705, Paris, France.
[Vorspan, Florence; Guillem, Eric; Bloch, Vanessa; Bellais, Laetitia; Noble, Florence; Lepine, Jean-Pierre] Univ Paris Diderot, CNRS, UMR 7157, INSERM,U705, Paris, France.
RP Vorspan, F (reprint author), Hop Fernand Widal, AP HP, Psychiat Serv, 200 Rue Fg St Denis, F-75475 Paris 10, France.
EM florence.vorspan@lrb.aphp.fr
OI Vorspan, Florence/0000-0001-5168-3727
FU Intramural NIH HHS [ZIA DA000240-17]
NR 5
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
J9 SLEEP MED
JI Sleep Med.
PD MAY
PY 2010
VL 11
IS 5
BP 499
EP 500
DI 10.1016/j.sleep.2009.12.001
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 598ZF
UT WOS:000277878500015
PM 20138005
ER
PT J
AU Vidal, JS
Sigurdsson, S
Jonsdottir, MK
Eiriksdottir, G
Thorgeirsson, G
Kjartansson, O
Garcia, ME
van Buchem, MA
Harris, TB
Gudnason, V
Launer, LJ
AF Vidal, Jean-Sebastien
Sigurdsson, Sigurdur
Jonsdottir, Maria K.
Eiriksdottir, Gudny
Thorgeirsson, Gudmundur
Kjartansson, Olafur
Garcia, Melissa E.
van Buchem, Mark A.
Harris, Tamara B.
Gudnason, Vilmundur
Launer, Lenore J.
TI Coronary Artery Calcium, Brain Function and Structure The AGES-Reykjavik
Study
SO STROKE
LA English
DT Article
DE atherosclerosis; calcinosis; cognitive function; coronary artery
disease; dementia; radiography
ID INTIMA-MEDIA THICKNESS; ANKLE-BRACHIAL INDEX; COGNITIVE IMPAIRMENT;
BLOOD-PRESSURE; CEREBROVASCULAR-DISEASE; ATHEROSCLEROSIS MESA;
DIABETES-MELLITUS; RISK; POPULATION; CALCIFICATION
AB Background and Purpose-Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function.
Methods-This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function.
Results-Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes.
Conclusions-In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology. (Stroke. 2010;41:891-897.)
C1 [Launer, Lenore J.] NIA, NIH, LEDB, Intramural Res Program, Bethesda, MD 20892 USA.
[Sigurdsson, Sigurdur; Jonsdottir, Maria K.; Eiriksdottir, Gudny; Kjartansson, Olafur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Jonsdottir, Maria K.] Univ Iceland, Fac Psychol, Reykjavik, Iceland.
[Thorgeirsson, Gudmundur; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Kjartansson, Olafur] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland.
[Kjartansson, Olafur] Landspitali Univ Hosp, Dept Radiol, Reykjavik, Iceland.
[van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Launer, LJ (reprint author), NIA, NIH, LEDB, Intramural Res Program, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA.
EM launerl@mail.nih.gov
RI Gudnason, Vilmundur/K-6885-2015; Vidal, Jean-Sebastien/D-1941-2016
OI Gudnason, Vilmundur/0000-0001-5696-0084; Vidal,
Jean-Sebastien/0000-0001-6770-0720
FU National Institutes of Health [N01-AG-1-2100]; National Institute on
Aging Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament)
FX This study was supported by a grant from the National Institutes of
Health (N01-AG-1-2100), National Institute on Aging Intramural Research
Program, the Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament).
NR 35
TC 51
Z9 52
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2010
VL 41
IS 5
BP 891
EP 897
DI 10.1161/STROKEAHA.110.579581
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 588IY
UT WOS:000277064300011
PM 20360538
ER
PT J
AU Saver, JL
Filip, B
Hamilton, S
Yanes, A
Craig, S
Cho, M
Conwit, R
Starkman, S
AF Saver, Jeffrey L.
Filip, Bogdan
Hamilton, Scott
Yanes, Anna
Craig, Sharon
Cho, Michelle
Conwit, Robin
Starkman, Sidney
CA FAST-MAG Investigators Coordinator
TI Improving the Reliability of Stroke Disability Grading in Clinical
Trials and Clinical Practice The Rankin Focused Assessment (RFA)
SO STROKE
LA English
DT Article
DE cerebral infarction; clinical trial; disability; outcomes; scales
ID STRUCTURED INTERVIEW; OUTCOME MEASURES; SCALE
AB Background and Purpose-The modified Rankin Scale rates global disability after stroke and is the most comprehensive and widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability in modified Rankin Scale scoring has been reported. This study sought to develop and validate a short, practicable structured assessment that would enhance interrater reliability.
Methods-The Rankin Focused Assessment was developed by selecting and refining elements from prior instruments. The Rankin Focused Assessment takes 3 to 5 minutes to apply and provides clear, operationalized criteria to distinguish the 7 assignable global disability levels. The Rankin Focused Assessment was prospectively validated 3 months poststroke among 50 consecutive patients enrolled in the Phase 3 National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial.
Results-Among the 50 patients, mean age was 71.5 years (range, 43 to 93 years), 48% were female, and stroke subtype was hemorrhagic in 24%. At Day 90, 43 patients were alive and 7 had died. The modified Rankin Scale median was 2.0 and mean was 2.8. When pairs of 14 raters assessed all enrolled patients, the percent agreement was 94%, the weighted kappa was 0.99 (95% CI, 0.99 to 1.0), and the unweighted kappa was 0.93 (95% CI, 0.85 to 1.00). Among the 43 surviving patients, the percent agreement was 93%, the weighted kappa was 0.99 (0.98 to 1.0), and the unweighted kappa was 0.91 (0.82 to 1.00).
Conclusions-The Rankin Focused Assessment yields high interrater reliability in the grading of final global disability among consecutive patients with stroke participating in a randomized clinical trial. The Rankin Focused Assessment is brief and practical for use in multicenter clinical trials and quality improvement activities. (Stroke. 2010;41:992-995.)
C1 [Saver, Jeffrey L.; Filip, Bogdan; Yanes, Anna; Craig, Sharon; Cho, Michelle; Starkman, Sidney] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA 90095 USA.
[Saver, Jeffrey L.; Filip, Bogdan; Yanes, Anna; Craig, Sharon; Cho, Michelle; Starkman, Sidney] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
[Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA.
[Conwit, Robin] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@ucla.edu
OI Saver, Jeffrey/0000-0001-9141-2251
FU National Institutes of Health-National Institute of Neurological
Disorders and Stroke [U01 NS 44364]
FX This study was supported by National Institutes of Health-National
Institute of Neurological Disorders and Stroke Award U01 NS 44364.
NR 14
TC 41
Z9 42
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2010
VL 41
IS 5
BP 992
EP 995
DI 10.1161/STROKEAHA.109.571364
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 588IY
UT WOS:000277064300027
PM 20360551
ER
PT J
AU Asensio, S
Romero, MJ
Romero, FJ
Wong, C
Alia-Klein, N
Tomasi, D
Wang, GJ
Telang, F
Volkow, ND
Goldstein, RZ
AF Asensio, Samuel
Romero, Maria J.
Romero, Francisco J.
Wong, Christopher
Alia-Klein, Nelly
Tomasi, Dardo
Wang, Gene-Jack
Telang, Frank
Volkow, Nora D.
Goldstein, Rita Z.
TI Striatal Dopamine D2 Receptor Availability Predicts the Thalamic and
Medial Prefrontal Responses to Reward in Cocaine Abusers Three Years
Later
SO SYNAPSE
LA English
DT Article
DE fMRI; PET; striatal dopamine D2 receptor availability; thalamus;
prefrontal cortex; cocaine addiction; monetary reward
ID LONG-TERM STABILITY; MONETARY REWARD; HUMAN BRAIN; DRUG-ABUSE;
ADDICTION; BINDING; EXPECTATION; SENSITIVITY; METABOLISM; ACTIVATION
AB Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [(11)C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals. Synapse 64:397-402, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Goldstein, Rita Z.] Brookhaven Natl Lab, Med Res Ctr, Upton, NY 11973 USA.
[Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.] Univ CEU Cardenal Herrera, Inst Drogas & Conductas Adictivas, Valencia 46113, Spain.
[Volkow, Nora D.] Natl Inst Drug Abuse, Neuro Sci Ctr, Bethesda, MD USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Med Res Ctr, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
RI Tomasi, Dardo/J-2127-2015; Asensio, Samuel/I-9426-2014
OI Asensio, Samuel/0000-0002-3028-6981
FU National Institute on Drug Abuse [IR01DA023579, R21DA02062]; Ministerio
de Ciencia e Innovacion Spain [SAF2007-66,801]; Instituto de Salud
Carlos III [RD06/000110032]; General Clinical Research Center
[5-MO1-RR-10,710]; U.S. Department of Energy (OBER)
FX Contract grant sponsor: National Institute on Drug Abuse; Contract grant
numbers: IR01DA023579, R21DA02062; Contract grant sponsor: Ministerio de
Ciencia e Innovacion Spain; Contract grant number: SAF2007-66,801;
Contract grant sponsor: RTA (Red de Transtornos Adictivos) program from
Instituto de Salud Carlos III; Contract grant number: RETICS
RD06/000110032; Contract grant sponsor: General Clinical Research
Center; Contract grant number: 5-MO1-RR-10,710; Contract grant sponsor:
Laboratory Directed Research and Development from U.S. Department of
Energy (OBER)
NR 31
TC 28
Z9 28
U1 3
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD MAY
PY 2010
VL 64
IS 5
BP 397
EP 402
DI 10.1002/syn.20741
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 573PU
UT WOS:000275927500006
PM 20034014
ER
PT J
AU Carretero, R
Cabrera, T
Rodriguez, AI
Wang, E
Engle, A
Ascierto, ML
Camacho, F
Marincola, FM
Garrido, F
AF Carretero, Rafael
Cabrera, Teresa
Rodriguez, Ana I.
Wang, Ena
Engle, Alyson
Ascierto, Maria L.
camacho, Francisco
Marincola, Francesco M.
Garrido, Federico
TI Regression of melanoma metastases is associated with activation of genes
involved in antigen presentation and immune mediated rejection
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 24th European Immunogenetics and Histocompatibility Conference/17th
Annual Meeting of the
Italian-Society-for-Immunogenetics-and-Transplantation-Biology
CY MAY 15-18, 2010
CL Florence, ITALY
SP Italian Soc Immunogenet & Transplantat Biol
C1 [Carretero, Rafael; Cabrera, Teresa] Univ Granada, Granada, Spain.
[Rodriguez, Ana I.; Garrido, Federico] Hosp Univ Virgen Nieves, Granada, Spain.
[Wang, Ena; Engle, Alyson; Ascierto, Maria L.; Marincola, Francesco M.] NIH, Bethesda, MD 20892 USA.
[camacho, Francisco] Hosp Univ Virgen Macarena, Seville, Spain.
RI Ascierto, Maria Libera/A-9239-2012; Cabrera, Teresa/L-5332-2015
OI Cabrera, Teresa/0000-0002-9871-1374
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD MAY
PY 2010
VL 75
IS 5
BP 469
EP 469
PG 1
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 583FO
UT WOS:000276659100010
ER
PT J
AU Hollenbach, JA
Erlich, H
Feolo, M
Fernandez-Vina, M
Gourraud, PA
Helmberg, W
Kanga, U
Kupatawintu, P
Lancaster, A
Maiers, M
Maldonado-Torres, H
Marsh, SGE
Meyers, D
Middleton, D
Muller, CR
Nathalang, O
Park, MH
Single, RM
Tait, B
Thomson, G
Valdes, AM
Varney, M
Mack, SJ
AF Hollenbach, Jill A.
Erlich, Henry
Feolo, Michael
Fernandez-Vina, Marcelo
Gourraud, Pierre-Antoine
Helmberg, Wolfgang
Kanga, Uma
Kupatawintu, Pawinee
Lancaster, Alex
Maiers, Martin
Maldonado-Torres, Hazael
Marsh, Steven G. E.
Meyers, Diogo
Middleton, Derek
Mueller, Carlheinz R.
Nathalang, Oytip
Park, Myoung Hee
Single, Richard M.
Tait, Brian
Thomson, Glenys
Valdes, Ana Maria
Varney, Mike
Mack, Steven J.
TI Toward a community standard for immunogenetics data reporting and
analysis
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 24th European Immunogenetics and Histocompatibility Conference/17th
Annual Meeting of the
Italian-Society-for-Immunogenetics-and-Transplantation-Biology
CY MAY 15-18, 2010
CL Florence, ITALY
SP Italian Soc Immunogenet & Transplantat Biol
C1 [Hollenbach, Jill A.; Mack, Steven J.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Erlich, Henry] Roche, Mol Syst, Pleasanton, CA USA.
[Feolo, Michael] NIH, Bethesda, MD 20892 USA.
[Fernandez-Vina, Marcelo] Univ Texas Houston, Houston, TX USA.
[Gourraud, Pierre-Antoine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Helmberg, Wolfgang] Med Univ Graz, Graz, Austria.
[Kanga, Uma] All India Inst Med Sci, New Delhi, India.
[Kupatawintu, Pawinee; Nathalang, Oytip] Natl Blood Ctr, Thai Red Cross Soc, Bangkok, Thailand.
[Lancaster, Alex] Univ Arizona, Tucson, AZ USA.
[Maiers, Martin] Natl Marrow Donor Program, Minneapolis, MN USA.
[Maldonado-Torres, Hazael; Marsh, Steven G. E.] Royal Free Hosp, London NW3 2QG, England.
[Meyers, Diogo] Univ Sao Paulo, Sao Paulo, Brazil.
[Middleton, Derek] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England.
[Mueller, Carlheinz R.] Bundesrepublik Deutschland GmbH, Zentrales Knochenmarkspender Register, Ulm, Germany.
[Park, Myoung Hee] Seoul Natl Univ Hosp, Seoul 110744, South Korea.
[Single, Richard M.] Univ Vermont, Burlington, VA USA.
[Tait, Brian; Varney, Mike] Australian Red Cross Blood Serv, Melbourne, Vic, Australia.
[Thomson, Glenys] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Valdes, Ana Maria] Kings Coll London, St Thomas Hosp, London WC2R 2LS, England.
RI Lancaster, Alex/K-2855-2013; Gourraud, Pierre-Antoine/O-3024-2015
OI Lancaster, Alex/0000-0002-0002-9263;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD MAY
PY 2010
VL 75
IS 5
BP 532
EP 533
PG 2
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 583FO
UT WOS:000276659100169
ER
PT J
AU Oliveira, LA
Carrington, M
Pereira, NF
Beltrame, MH
Petzl-Erler, ML
AF Oliveira, Liana A.
Carrington, Mary
Pereira, Noemi F.
Beltrame, Marcia H.
Petzl-Erler, Maria-Luiza
TI Susceptibility loci to pemphigus foliaceus in the major
histocompatibility complex
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 24th European Immunogenetics and Histocompatibility Conference/17th
Annual Meeting of the
Italian-Society-for-Immunogenetics-and-Transplantation-Biology
CY MAY 15-18, 2010
CL Florence, ITALY
SP Italian Soc Immunogenet & Transplantat Biol
C1 [Oliveira, Liana A.; Pereira, Noemi F.; Beltrame, Marcia H.; Petzl-Erler, Maria-Luiza] Univ Fed Parana, BR-80060000 Curitiba, PR, Brazil.
[Carrington, Mary] NCI Frederick, Frederick, MD USA.
RI Petzl-Erler, Maria-Luiza/H-8221-2012
OI Petzl-Erler, Maria-Luiza/0000-0002-0345-5276
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD MAY
PY 2010
VL 75
IS 5
BP 629
EP 629
PG 1
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 583FO
UT WOS:000276659100415
ER
PT J
AU Olivero, OA
Vazquez, IL
Cooch, CC
Ming, J
Keller, E
Yu, M
Borojerdi, JP
Braun, HM
McKee, E
Poirier, MC
AF Olivero, Ofelia A.
Vazquez, Irma L.
Cooch, Catherine C.
Ming, Jessica
Keller, Emily
Yu, Mia
Borojerdi, Jennifer P.
Braun, Hannan M.
McKee, Edward
Poirier, Miriam C.
TI Long-term AZT Exposure Alters the Metabolic Capacity of Cultured Human
Lymphoblastoid Cells
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE nucleoside analog; antiretrovirals; thymidine kinase
ID REVERSE-TRANSCRIPTASE INHIBITORS; T-LYMPHOID CELLS; THYMIDINE KINASE;
IN-VITRO; DEOXYCYTIDINE KINASE; AZIDOTHYMIDINE AZT; DRUG-RESISTANCE;
DIRECT GAVAGE; HELA-CELLS; ZIDOVUDINE
AB The antiretroviral efficacy of 3'-azido-3'-deoxythymidine (AZT) is dependent upon intracellular mono-, di-, and triphosphorylation and incorporation into DNA in place of thymidine. Thymidine kinase 1 (TK-1) catalyzes the first step of this pathway. MOLT-3, human lymphoblastoid cells, were exposed to AZT continuously for 14 passages (P(1)-P(14)) and cultured for an additional 14 passages (P(15)-P(28)) without AZT. Progressive and irreversible depletion of the enzymatically active form of the TK-1 24-kDa monomer with loss of active protein was demonstrated during P(1)-P(5) of AZT exposure. From P(15) to P(28), both the 24- and the 48-kDa forms of TK-1 were undetectable and a tetrameric 96-kDa form was present. AZT-DNA incorporation was observed with values of 150, 133, and 108 molecules of AZT/10(6) nucleotides at the 10 mu M plasma-equivalent AZT dose at P(1), P(5), and P(14), respectively. An exposure-related increase in the frequency of micronuclei (MN) was observed in cells exposed to either 10 or 800 mu M AZT during P(1)-P(14). Analysis of the cell cycle profile revealed an accumulation of S-phase cells and a decrease in G(1)-phase cells during exposure to 800 mu M AZT for 14 passages. When MOLT-3 cells were grown in AZT-free media (P(15)-P(29)), there was a reduction in AZT-DNA incorporation and MN formation; however, TK-1 depletion and the persistence of S-phase delay were unchanged. These data suggest that in addition to known mutagenic mechanisms, cells may become resistant to AZT partially through inactivation of TK-1 and through modulation of cell cycle components.
C1 [Olivero, Ofelia A.] NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA.
[McKee, Edward] Indiana Sch Med, S Bend Ctr Med Educ, Notre Dame, IN 46556 USA.
RP Olivero, OA (reprint author), NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, NIH, 37 Convent Dr MSC 4255,Bldg 37 Rm 4032, Bethesda, MD 20892 USA.
EM oliveroo@exchange.nih.gov
FU NIH, National Cancer Institute; Center for Cancer Research
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 40
TC 9
Z9 9
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 MAY
PY 2010
VL 115
IS 1
BP 109
EP 117
DI 10.1093/toxsci/kfq023
PG 9
WC Toxicology
SC Toxicology
GA 584HN
UT WOS:000276742200011
PM 20106944
ER
PT J
AU Sadrieh, N
Wokovich, AM
Gopee, NV
Zheng, JW
Haines, D
Parmiter, D
Siitonen, PH
Cozart, CR
Patri, AK
McNeil, SE
Howard, PC
Doub, WH
Buhse, LF
AF Sadrieh, Nakissa
Wokovich, Anna M.
Gopee, Neera V.
Zheng, Jiwen
Haines, Diana
Parmiter, David
Siitonen, Paul H.
Cozart, Christy R.
Patri, Anil K.
McNeil, Scott E.
Howard, Paul C.
Doub, William H.
Buhse, Lucinda F.
TI Lack of Significant Dermal Penetration of Titanium Dioxide from
Sunscreen Formulations Containing Nano- and Submicron-Size TiO2
Particles
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE Sunscreen; TiO2; Nano; skin
ID QUANTUM DOTS; IN-VITRO; ZINC-OXIDE; SKIN; NANOPARTICLES; ABSORPTION
AB Titanium dioxide (TiO2) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO2 particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the TiO2 content was determined (as titanium) using inductively coupled plasma mass spectroscopy. Titanium levels in lymph nodes and liver from treated animals were not increased over the values in control animals. The epidermis from minipigs treated with sunscreens containing TiO2 showed elevated titanium. Increased titanium was detected in abdominal and neck dermis of minipigs treated with uncoated and coated nanoscale TiO2. Using electron microscopy-energy dispersive x-ray analysis, all three types of TiO2 particles were found in the stratum corneum and upper follicular lumens in all treated skin samples (more particles visible with coated nanoscale TiO2). Isolated titanium particles were also present at various locations in the dermis of animals treated with all three types of TiO2-containing sunscreens; however, there was no pattern of distribution or pathology suggesting the particles could be the result of contamination. At most, the few isolated particles represent a tiny fraction of the total amount of applied TiO2. These findings indicate that there is no significant penetration of TiO2 nanoparticles through the intact normal epidermis.
C1 [Sadrieh, Nakissa] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, St Louis, MO 63101 USA.
[Gopee, Neera V.; Siitonen, Paul H.; Cozart, Christy R.; Howard, Paul C.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zheng, Jiwen; Haines, Diana; Parmiter, David; Patri, Anil K.; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Haines, Diana] NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Sadrieh, N (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM nakissa.sadrieh@fda.hhs.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute; National Institutes of Health [N01-CO-12400,
HHSN261200800001E]
FX National Cancer Institute and the National Institutes of Health under
contracts N01-CO-12400 and HHSN261200800001E.
NR 34
TC 112
Z9 114
U1 4
U2 54
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAY
PY 2010
VL 115
IS 1
BP 156
EP 166
DI 10.1093/toxsci/kfq041
PG 11
WC Toxicology
SC Toxicology
GA 584HN
UT WOS:000276742200015
PM 20156837
ER
PT J
AU Luke, NS
Sams, R
DeVito, MJ
Conolly, RB
El-Masri, HA
AF Luke, Nicholas S.
Sams, Reeder, II
DeVito, Michael J.
Conolly, Rory B.
El-Masri, Hisham A.
TI Development of a Quantitative Model Incorporating Key Events in a
Hepatotoxic Mode of Action to Predict Tumor Incidence
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE quantitative modeling; risk assessment; mode of action
ID DOSE-RESPONSE RELATIONSHIPS; CANCER-RISK ASSESSMENT; INDUCED LIVER
DAMAGE; CARBON-TETRACHLORIDE; INHALATION EXPOSURE; CHRONIC TOXICITY;
PHARMACOKINETIC MODELS; PARTITION-COEFFICIENTS; CHLOROFORM INHALATION;
DEPENDENT TRANSITIONS
AB Biologically based dose-response (BBDR) modeling of environmental pollutants can be utilized to inform the mode of action (MOA) by which compounds elicit adverse health effects. Chemicals that produce tumors are typically labeled as either genotoxic or nongenotoxic. Though both the genotoxic and the nongenotoxic MOA may be operative as a function of dose, it is important to note that the label informs but does not define a MOA. One commonly proposed MOA for nongenotoxic carcinogens is characterized by the key events cytotoxicity and regenerative proliferation. The increased division rate associated with such proliferation can cause an increase in the probability of mutations, which may result in tumor formation. We included these steps in a generalized computational pharmacodynamic (PD) model incorporating cytotoxicity as a MOA for three carcinogens (chloroform, CHCl(3); carbon tetrachloride, CCL(4); and N,N-dimethylformamide, DMF). For each compound, the BBDR model is composed of a chemical-specific physiologically based pharmacokinetic model linked to a PD model of cytotoxicity and cellular proliferation. The rate of proliferation is then linked to a clonal growth model to predict tumor incidences. Comparisons of the BBDR simulations and parameterizations across chemicals suggested that significant variation among the models for the three chemicals arises in a few parameters expected to be chemical specific (such as metabolism and cellular injury rate constants). Optimization of model parameters to tumor data for CCL(4) and DMF resulted in similar estimates for all parameters related to cytotoxicity and tumor incidences. However, optimization of the CHCl(3) data resulted in a higher estimate for one parameter (BD) related to death of initiated cells. This implies that additional steps beyond cytotoxicity leading to induced cellular proliferation can be quantitatively different among chemicals that share cytotoxicity as a hypothesized carcinogenic MOA.
C1 [Conolly, Rory B.; El-Masri, Hisham A.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Luke, Nicholas S.] N Carolina Agr & Tech State Univ, Dept Math, Greensboro, NC 27411 USA.
[Sams, Reeder, II] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[DeVito, Michael J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP El-Masri, HA (reprint author), US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, 109 TW Alexander Dr,Mail Drop B143-01, Res Triangle Pk, NC 27711 USA.
EM el-masri.hisham@epa.gov
NR 60
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U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAY
PY 2010
VL 115
IS 1
BP 253
EP 266
DI 10.1093/toxsci/kfq021
PG 14
WC Toxicology
SC Toxicology
GA 584HN
UT WOS:000276742200023
PM 20106946
ER
PT J
AU Lebeda, FJ
Cer, RZ
Mudunuri, U
Stephens, R
Singh, BR
Adler, M
AF Lebeda, Frank J.
Cer, Regina Z.
Mudunuri, Uma
Stephens, Robert
Singh, Bal Ram
Adler, Michael
TI The Zinc-Dependent Protease Activity of the Botulinum Neurotoxins
SO TOXINS
LA English
DT Review
DE catalysis; energy; k(cat); K-m; superactivation
AB The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism. Following exposure, the neurotoxin binds and enters peripheral cholinergic nerve endings and specifically and selectively cleaves one or more SNARE proteins to produce flaccid paralysis. This review centers on the kinetics of the Zn-dependent proteolytic activities of these neurotoxins, and briefly describes inhibitors, activators and factors underlying persistence of toxin action. Some of the structural, enzymatic and inhibitor data that are discussed here are available at the botulinum neurotoxin resource, BotDB (http://botdb.abcc.ncifcrf.gov).
C1 [Lebeda, Frank J.] USA, Med Res & Mat Command, Ft Detrick, MD 21702 USA.
[Cer, Regina Z.; Mudunuri, Uma; Stephens, Robert] NCI Frederick, Bioinformat Support Grp, Adv Biomed Comp Ctr, Informat Syst Program,SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
[Singh, Bal Ram] Univ Massachusetts, Botulinum Res Ctr, Dartmouth, MA 02747 USA.
[Adler, Michael] USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA.
RP Lebeda, FJ (reprint author), USA, Med Res & Mat Command, Ft Detrick, MD 21702 USA.
EM frank.lebeda@amedd.army.mil; cerr@mail.nih.gov; mudunuriu@mail.nih.gov;
stephensr@mail.nih.gov; bsingh@umassd.edu; michael.adler@us.army.mil
FU Defense Threat Reduction Agency, Joint Science and Technology
Office-Chemical Biological Defense [3.10043-07-RD-B, T.T.0011-06-RC_B];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This study was supported by the Defense Threat Reduction Agency, Joint
Science and Technology Office-Chemical Biological Defense project
3.10043-07-RD-B (FJL), and project T.T.0011-06-RC_B (MA) and by the
National Cancer Institute, National Institutes of Health under contract
HHSN261200800001E. Opinions, interpretations, conclusions, and
recommendations are those of the authors and are not necessarily
endorsed by the U. S. Army or the Department of Health and Human
Services. The mention of trade names, commercial products, or
organizations does not imply endorsement by the U. S. Government.
Electronic versions for some of the citations used in the analysis for
this paper were obtained at the National Library of Medicine, the
Uniform Services University of the Health Sciences and the Sheridan
Libraries at Johns Hopkins University.
NR 100
TC 10
Z9 12
U1 1
U2 11
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD MAY
PY 2010
VL 2
IS 5
BP 978
EP 997
DI 10.3390/toxins2050978
PG 20
WC Toxicology
SC Toxicology
GA V24UI
UT WOS:000208434900004
PM 22069621
ER
PT J
AU Wilson, DM
Seidman, MM
AF Wilson, David M., III
Seidman, Michael M.
TI A novel link to base excision repair?
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID INTERSTRAND CROSS-LINKS; 3-METHYLADENINE DNA GLYCOSYLASE;
SACCHAROMYCES-CEREVISIAE; LESION RECOGNITION; MAMMALIAN-CELLS;
MOLECULAR-BASIS; DAMAGED DNA; PSORALEN; ADDUCTS; PATHWAY
AB DNA interstrand crosslinks (ICLs) can arise from reactions with endogenous chemicals, such as malondialdehyde - a lipid peroxidation product or from exposure to various clinical anti-cancer drugs, most notably bifunctional alkylators and platinum compounds. Because they covalently link the two strands of DNA, ICLs completely block transcription and replication, and, as a result, are lethal to the cell. It is well established that proteins that function in nucleotide excision repair and homologous recombination are involved in ICL resolution. Recent work, coupled with a much earlier report, now suggest an emerging link between proteins of the base excision repair pathway and crosslink processing.
C1 [Wilson, David M., III; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, IRP,BRC, Baltimore, MD 21224 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, IRP,BRC, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU Intramural NIH HHS [ZIA AG000743-08]
NR 53
TC 13
Z9 13
U1 0
U2 3
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD MAY
PY 2010
VL 35
IS 5
BP 247
EP 252
DI 10.1016/j.tibs.2010.01.003
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 607JF
UT WOS:000278497800001
PM 20172733
ER
PT J
AU Nader, N
Chrousos, GP
Kino, T
AF Nader, Nancy
Chrousos, George P.
Kino, Tomoshige
TI Interactions of the circadian CLOCK system and the HPA axis
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID MOUSE PERIPHERAL-TISSUES; PAI-1 GENE-EXPRESSION; REV-ERB-ALPHA;
METABOLIC SYNDROME; SUPRACHIASMATIC NUCLEUS; TRANSCRIPTION FACTOR; STRIA
TERMINALIS; STRESS SYSTEM; ADRENAL-GLAND; OVAL NUCLEUS
AB Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with one another at different signaling levels and dysregulation of either system can lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.
C1 [Nader, Nancy; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, 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, Bethesda, MD
FX Literary work of this article was funded partly by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health,
Bethesda, MD.
NR 64
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U1 2
U2 22
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD MAY
PY 2010
VL 21
IS 5
BP 277
EP 286
DI 10.1016/j.tem.2009.12.011
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 609RK
UT WOS:000278674600003
PM 20106676
ER
PT J
AU Schorge, S
van de Leemput, J
Singleton, A
Houlden, H
Hardy, J
AF Schorge, Stephanie
van de Leemput, Joyce
Singleton, Andrew
Houlden, Henry
Hardy, John
TI Human ataxias: a genetic dissection of inositol triphosphate receptor
(ITPR1)-dependent signaling
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID LONG-TERM DEPRESSION; CEREBELLAR PURKINJE NEURONS; KINASE-C-GAMMA;
SPINOCEREBELLAR ATAXIA; GLUTAMATE TRANSPORTERS; 1,4,5-TRISPHOSPHATE
RECEPTOR; K+ CHANNELS; SENSORINEURAL DEAFNESS; SYNAPTIC PLASTICITY;
CALCIUM-RELEASE
AB A persistent mystery about the ataxias has been why mutations in genes - many of which are expressed widely in the brain - primarily cause ataxia, and not, for example, epilepsy or dementia. Why should a polyglutamine stretch in the TATA-binding protein (that is important in all cells) particularly disrupt cerebellar coordination? We propose that advances in the genetics of cerebellar ataxias suggest a rational hypothesis for how so many different genes lead to predominantly cerebellar defects. We argue that the unifying feature of many genes involved in cerebellar ataxias is their impact on the signaling protein ITPR1 (inositiol 1,4,5-triphosphate receptor type 1), that underlies coincidence detection in Purkinje cells
C1 [Schorge, Stephanie; van de Leemput, Joyce; Singleton, Andrew; Houlden, Henry; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
[Schorge, Stephanie; van de Leemput, Joyce; Singleton, Andrew; Houlden, Henry; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[van de Leemput, Joyce; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Hardy, J (reprint author), UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
EM j.hardy@ion.ucl.ac.uk
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Houlden,
Henry/C-1532-2008;
OI Houlden, Henry/0000-0002-2866-7777; Schorge,
Stephanie/0000-0003-1541-5148
FU Department of Health's National Institute for Health Research Biomedical
Research Center; MRC; Ataxia UK; Wellcome Trust; Worshipful Company of
Pewterers; National Institute on Aging, National Institutes of Health;
Department of Health and Human Services; [Z01 AG000958-06]
FX This work was undertaken at University College London Hospital (UCLH)
and University College London (UCL) with support from the Department of
Health's National Institute for Health Research Biomedical Research
Centers funding scheme. Work in our laboratories is sponsored by the
MRC, Ataxia UK, and the Wellcome Trust. S.S. holds a fellowship from the
Worshipful Company of Pewterers. This work was supported in part by the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services; project
Z01 AG000958-06.
NR 92
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U1 0
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD MAY
PY 2010
VL 33
IS 5
BP 211
EP 219
DI 10.1016/j.tins.2010.02.005
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 610SB
UT WOS:000278754300001
PM 20226542
ER
PT J
AU Lerner, SP
Grossman, HB
Messing, EM
Kibel, AS
Stephenson, A
Gee, JR
O'Donnell, MA
Reid, RD
Kamat, AM
Parnes, HL
House, MG
AF Lerner, Seth P.
Grossman, H. Barton
Messing, Edward M.
Kibel, Adam S.
Stephenson, Andrew
Gee, Jason R.
O'Donnell, Michael A.
Reid, Robert D.
Kamat, Ashish M.
Parnes, Howard L.
House, Margaret G.
TI BCAN Think Tank session 3: Prevention of bladder cancer
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article; Proceedings Paper
CT 3rd Annual Bladder Cancer Think Tank
CY AUG, 2008
CL Mont Tremblant, CANADA
DE Bladder cancer; Chemoprevention; Smoking cessation; Second primary
tumors; Bacille Calmette-Guerin; Biomarkers
ID TOBACCO SMOKING; TRIAL; RECURRENCE; RISK; IFN
AB The Bladder Cancer Think Tank III brought together a multidisciplinary group of clinician scientists, patient advocates, representatives from the National Cancer Institute, and Industry leaders to discuss the current state of the field in urothelial cancer and to develop strategies to move forward. This paper summarizes the session devoted to prevention. Experts sought to define primary, secondary, and tertiary prevention and discussed clinical trials performed to date testing retinoids, difluoromethylornithine, celecoxib, and other oral agents in a tertiary prevention setting following transurethral resection with or without intravesical therapy. Urologists practice tertiary prevention in the form of intravesical therapy, and strategies were discussed to identify biomarkers, including urinary cytokines and pathway single nucleotide polymorphism analysis associated with response to treatment. Optimizing delivery of intravesical chemotherapy to the target tissue with simple pharmacologic manipulations or packaging drugs in nanoparticles may improve treatment outcome. Defining a premalignant lesion should be a focus of future research as a strategy for early detection and secondary prevention. Cigarette smoking is the most prevalent risk factor for urothelial cancer, and emphasis was placed on smoking cessation as a powerful tool to reduce the burden of urothelial cancer, and the central role physicians must play in educating patients and providing resources. There is a strong need for research to develop markers of disease initiation and progression. These markers, combined with histories of environmental exposure to bladder carcinogens, may provide a tool to identify patients who will benefit from primary prevention. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lerner, Seth P.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
[Grossman, H. Barton; Kamat, Ashish M.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Messing, Edward M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Kibel, Adam S.] Washington Univ, Div Urol Surg, Sch Med, St Louis, MO 63110 USA.
[Stephenson, Andrew] Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA.
[Gee, Jason R.] Dept Urol, Madison, WI 53792 USA.
[O'Donnell, Michael A.] Univ Iowa, Iowa City, IA 52242 USA.
[Reid, Robert D.] Univ Ottawa, Inst Heart, Minto Prevent & Rehabil Ctr, Ottawa, ON, Canada.
[Parnes, Howard L.; House, Margaret G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Lerner, SP (reprint author), Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
EM slerner@bcm.tmc.edu
NR 17
TC 4
Z9 4
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD MAY-JUN
PY 2010
VL 28
IS 3
BP 338
EP 342
DI 10.1016/j.urolonc.2009.06.018
PG 5
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 601ED
UT WOS:000278040100020
PM 20439034
ER
PT J
AU Basch, E
Reeve, B
Cleeland, C
Sloan, J
Mendoza, T
Abernethy, A
Bruner, D
Hay, J
Atkinson, T
Sit, L
Minasian, L
O'Mara, A
Burke, L
Schrag, D
AF Basch, E.
Reeve, B.
Cleeland, C.
Sloan, J.
Mendoza, T.
Abernethy, A.
Bruner, D.
Hay, J.
Atkinson, T.
Sit, L.
Minasian, L.
O'Mara, A.
Burke, L.
Schrag, D.
TI DEVELOPMENT OF THE PATIENT-REPORTED VERSION OF THE COMMON TERMINOLOGY
CRITERIA FOR ADVERSE EVENTS ( PRO-CTCAE)
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Basch, E.; Hay, J.; Atkinson, T.; Sit, L.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Reeve, B.; Minasian, L.; O'Mara, A.] Natl Canc Inst, Bethesda, MD USA.
[Cleeland, C.; Mendoza, T.] UTMD Anderson Canc Ctr, Houston, TX USA.
[Sloan, J.] Mayo Clin, Rochester, MN USA.
[Abernethy, A.] Duke Univ, Durham, NC USA.
[Bruner, D.] Univ Penn, Philadelphia, PA 19104 USA.
[Burke, L.] Food & Drug Adm, Silver Spring, MD USA.
[Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2010
VL 13
IS 3
BP A44
EP A44
DI 10.1016/S1098-3015(10)72198-7
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 589CJ
UT WOS:000277121900215
ER
PT J
AU Hao, X
Fredrickson, TN
Chattopadhyay, SK
Han, W
Qi, CF
Wang, Z
Ward, JM
Hartley, JW
Morse, HC
AF Hao, X.
Fredrickson, T. N.
Chattopadhyay, S. K.
Han, W.
Qi, C. -F.
Wang, Z.
Ward, J. M.
Hartley, J. W.
Morse, H. C., III
TI The Histopathologic and Molecular Basis for the Diagnosis of Histiocytic
Sarcoma and Histiocyte-Associated Lymphoma of Mice
SO VETERINARY PATHOLOGY
LA English
DT Article
DE histiocytic sarcoma; histiocyte-associated lymphoma;
immunohistochemistry; lymphoma; Southern blotting; tissue microarray
ID B-CELL LYMPHOMA; T-CELL; HEMATOPOIETIC NEOPLASMS;
DIFFERENTIAL-DIAGNOSIS; BETHESDA PROPOSALS; MYELOID LINEAGES;
BONE-MARROW; CHAIN GENE; MOUSE; EXPRESSION
AB Histiocytic sarcoma (HS) and histiocyte associated lymphoma (HAL) of mice are difficult to distinguish histologically. Studies of multiple cases initially diagnosed as HS or HAL allowed us to define HS as round, fusiform, or mixed cell types that were F4/80+, Mac-2+, and PAX5-; that lacked markers for other sarcomas; and that had immune receptor genes in germline configuration. Two other subsets had clonal populations of lymphocytes. The first, HAL, featured malignant lymphocytes admixed with large populations of normal appearing histiocytes. The second appeared to be composites of lymphoma and HS. Several cases suggestive of B myeloid lineage plasticity were also observed.
C1 [Hao, X.; Fredrickson, T. N.; Chattopadhyay, S. K.; Qi, C. -F.; Ward, J. M.; Hartley, J. W.; Morse, H. C., III] NIAID, Immunopathol Lab, Bethesda, MD 20892 USA.
[Hao, X.] Rutgers State Univ, Dept Biol Chem, Ernest Mario Sch Pharm, Piscataway, NJ USA.
[Han, W.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Wang, Z.] NIH, Rockville, MD USA.
[Wang, Z.] Henry M Jackson Fdn Advancement Mil Med, Rockville, MD USA.
RP Morse, HC (reprint author), NIAID, 5640 Fishers Lane,Room 1421, Rockville, MD 20852 USA.
EM hmorse@niaid.nih.gov
OI Morse, Herbert/0000-0002-9331-3705
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; National Cancer Institute; National Institute of
Allergy and Infectious Diseases
FX We thank Alfonso Macias for maintenance of the NFS.V+ mouse colony, for
monitoring disease, and for necropsies; we also thank National Institute
of Allergy and Infectious Diseases intramural editor Brenda Rae Marshall
for assistance in preparation of the article. This work was supported in
part by the Intramural Research Program of the National Institutes of
Health, National Institute of Allergy and Infectious Diseases, and
National Cancer Institute and in part by a National Institute of Allergy
and Infectious Diseases contract to SoBran Inc. Because X.H., T.N.F.,
W.H., J.M.W., C.-F.Q., J.W.H., and H.C.M. III are government employees
and this is a government work, the work is in the public domain in the
United States. Notwithstanding any other agreements, the National
Institutes of Health reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices. You can
establish rights outside of the United States subject to a government
use license.
NR 56
TC 16
Z9 16
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD MAY
PY 2010
VL 47
IS 3
BP 434
EP 445
DI 10.1177/0300985810363705
PG 12
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 593SH
UT WOS:000277480400005
PM 20472805
ER
PT J
AU Waheed, AA
Freed, EO
AF Waheed, Abdul A.
Freed, Eric O.
TI The Role of Lipids in Retrovirus Replication
SO VIRUSES-BASEL
LA English
DT Review
DE retroviruses; phospholipids; sphingolipids; cholesterol; PI(4,5)P(2);
lipid rafts; entry; assembly; budding
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TYPE-1 MATRIX
PROTEIN; GPI-ANCHORED PROTEINS; TO-CELL SPREAD; VIRION-ASSOCIATED
CHOLESTEROL; HIV-1 ENVELOPE GLYCOPROTEIN; ROUS-SARCOMA-VIRUS;
DETERGENT-RESISTANT MEMBRANES; B METHYL-ESTER
AB Retroviruses undergo several critical steps to complete a replication cycle. These include the complex processes of virus entry, assembly, and budding that often take place at the plasma membrane of the host cell. Both virus entry and release involve membrane fusion/fission reactions between the viral envelopes and host cell membranes. Accumulating evidence indicates important roles for lipids and lipid microdomains in virus entry and egress. In this review, we outline the current understanding of the role of lipids and membrane microdomains in retroviral replication.
C1 [Waheed, Abdul A.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Waheed, AA (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM awaheed@ncifcrf.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Intramural
AIDS Targeted Antiviral Program
FX We thank A. Ono, Q. Sattentau and C. Jolly for generously granting
permission to reproduce figures, and members of the Freed laboratory for
helpful discussions and critical review of the manuscript. We apologize
to our colleagues whose work was not adequately cited due to space
limitation. The Freed laboratory is supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research and by the Intramural AIDS Targeted Antiviral Program.
NR 221
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U1 0
U2 16
PU MDPI AG
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD MAY
PY 2010
VL 2
IS 5
BP 1146
EP 1180
DI 10.3390/v2051146
PG 35
WC Virology
SC Virology
GA 632HQ
UT WOS:000280413700006
PM 20740061
ER
PT J
AU Omelchenko, MV
Galperin, MY
Wolf, YI
Koonin, EV
AF Omelchenko, Marina V.
Galperin, Michael Y.
Wolf, Yuri I.
Koonin, Eugene V.
TI Non-homologous isofunctional enzymes: A systematic analysis of
alternative solutions in enzyme evolution
SO BIOLOGY DIRECT
LA English
DT Article
ID ARCHAEON PYROCOCCUS-FURIOSUS; TRANSFER-RNA SYNTHETASE; MOONLIGHTING
PROTEINS; SUPEROXIDE-DISMUTASE; ENOLASE SUPERFAMILY; ANALOGOUS ENZYMES;
STRUCTURAL GENOMICS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SCALE ANALYSIS
AB Background: Evolutionarily unrelated proteins that catalyze the same biochemical reactions are often referred to as analogous - as opposed to homologous - enzymes. The existence of numerous alternative, non-homologous enzyme isoforms presents an interesting evolutionary problem; it also complicates genome-based reconstruction of the metabolic pathways in a variety of organisms. In 1998, a systematic search for analogous enzymes resulted in the identification of 105 Enzyme Commission (EC) numbers that included two or more proteins without detectable sequence similarity to each other, including 34 EC nodes where proteins were known (or predicted) to have distinct structural folds, indicating independent evolutionary origins. In the past 12 years, many putative non-homologous isofunctional enzymes were identified in newly sequenced genomes. In addition, efforts in structural genomics resulted in a vastly improved structural coverage of proteomes, providing for definitive assessment of (non) homologous relationships between proteins.
Results: We report the results of a comprehensive search for non-homologous isofunctional enzymes (NISE) that yielded 185 EC nodes with two or more experimentally characterized - or predicted - structurally unrelated proteins. Of these NISE sets, only 74 were from the original 1998 list. Structural assignments of the NISE show over-representation of proteins with the TIM barrel fold and the nucleotide-binding Rossmann fold. From the functional perspective, the set of NISE is enriched in hydrolases, particularly carbohydrate hydrolases, and in enzymes involved in defense against oxidative stress.
Conclusions: These results indicate that at least some of the non-homologous isofunctional enzymes were recruited relatively recently from enzyme families that are active against related substrates and are sufficiently flexible to accommodate changes in substrate specificity.
Reviewers: This article was reviewed by Andrei Osterman, Keith F. Tipton (nominated by Martijn Huynen) and Igor B. Zhulin. For the full reviews, go to the Reviewers' comments section.
C1 [Omelchenko, Marina V.; Galperin, Michael Y.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM galperin@ncbi.nlm.nih.gov
RI Galperin, Michael/B-5859-2013
OI Galperin, Michael/0000-0002-2265-5572
FU National Library of Medicine at the National Institutes of Health; NIH
FX This work was supported by the Intramural Research Program of the
National Library of Medicine at the National Institutes of Health.
Funding to pay the Open Access publication charges for this article was
provided by the NIH Intramural Research Program.
NR 81
TC 50
Z9 51
U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD APR 30
PY 2010
VL 5
AR 31
DI 10.1186/1745-6150-5-31
PG 20
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 605PK
UT WOS:000278359300001
PM 20433725
ER
PT J
AU Wallander, JL
McClure, E
Biasini, F
Goudar, SS
Pasha, O
Chomba, E
Shearer, D
Wright, L
Thorsten, V
Chakraborty, H
Dhaded, SM
Mahantshetti, NS
Bellad, RM
Abbasi, Z
Carlo, W
AF Wallander, Jan L.
McClure, Elizabeth
Biasini, Fred
Goudar, Shivaprasad S.
Pasha, Omrana
Chomba, Elwyn
Shearer, Darlene
Wright, Linda
Thorsten, Vanessa
Chakraborty, Hrishikesh
Dhaded, Sangappa M.
Mahantshetti, Niranjana S.
Bellad, Roopa M.
Abbasi, Zahid
Carlo, Waldemar
CA BRAIN HIT Investigators
TI Brain Research to Ameliorate Impaired Neurodevelopment - Home-based
Intervention Trial (BRAIN-HIT)
SO BMC PEDIATRICS
LA English
DT Article
ID LOW-BIRTH-WEIGHT; SEVERELY MALNOURISHED CHILDREN; RANDOMIZED
CONTROLLED-TRIAL; PSYCHOSOCIAL STIMULATION; PREMATURE-INFANTS;
NUTRITIONAL SUPPLEMENTATION; INTELLECTUAL-DEVELOPMENT; DEVELOPMENT
PROGRAM; MENTAL-DEVELOPMENT; JAMAICAN CHILDREN
AB Background: This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low-and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low-and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low-and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia.
Methods/Design: This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors.
Discussion: The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.
C1 [Wallander, Jan L.] Univ Calif Merced, Psychol Sci & Hlth Sci Res Inst, Merced, CA 95343 USA.
[McClure, Elizabeth; Thorsten, Vanessa; Chakraborty, Hrishikesh] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC 27709 USA.
[Biasini, Fred] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA.
[Goudar, Shivaprasad S.] JN Med Coll, Dept Physiol, Belgaum 590010, Karnataka, India.
[Goudar, Shivaprasad S.] JN Med Coll, Dept Med Educ, Belgaum 590010, Karnataka, India.
[Pasha, Omrana; Abbasi, Zahid] Aga Khan Univ, Dept Community Hlth Sci, Karachi 74800, Pakistan.
[Pasha, Omrana; Abbasi, Zahid] Aga Khan Univ, Dept Family Med, Karachi 74800, Pakistan.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia.
[Shearer, Darlene] Western Kentucky Univ, Dept Publ Hlth, Bowling Green, KY 42101 USA.
[Wright, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Rockville, MD 20852 USA.
[Dhaded, Sangappa M.; Mahantshetti, Niranjana S.; Bellad, Roopa M.] JN Med Coll, Dept Pediat, Belgaum 590010, Karnataka, India.
[Carlo, Waldemar] Univ Alabama, Dept Pediat, Div Neonatol, Birmingham, AL 35233 USA.
RP Wallander, JL (reprint author), Univ Calif Merced, Psychol Sci & Hlth Sci Res Inst, 5200 Lake Rd, Merced, CA 95343 USA.
EM jwallander@ucmerced.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Eunice K Eunice Kennedy Shriver National Institute of Child Health and
Human Development [HD43464, HD42372, HD40607, HD40636]; Fogarty
International Center [R21 TW006703-02]; Division of Neonatology,
Department of Pediatrics, University of Alabama at Birmingham
FX Funded by grants from Eunice K Eunice Kennedy Shriver National Institute
of Child Health and Human Development (HD43464, HD42372, HD40607,
HD40636) and the Fogarty International Center (R21 TW006703-02), and by
the Division of Neonatology, Department of Pediatrics, University of
Alabama at Birmingham.
NR 61
TC 13
Z9 14
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD APR 30
PY 2010
VL 10
AR 27
DI 10.1186/1471-2431-10-27
PG 9
WC Pediatrics
SC Pediatrics
GA 603TR
UT WOS:000278231500001
PM 20433740
ER
PT J
AU Ji, YH
Resch, W
Corbett, E
Yamane, A
Casellas, R
Schatz, DG
AF Ji, Yanhong
Resch, Wolfgang
Corbett, Elizabeth
Yamane, Arito
Casellas, Rafael
Schatz, David G.
TI The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci
SO CELL
LA English
DT Article
ID HEAVY-CHAIN LOCUS; V(D)J RECOMBINATION; CHROMOSOMAL TRANSLOCATIONS;
HISTONE H3; SYNAPTIC COMPLEX; ACTIVE-SITE; DNA BREAKS; CLEAVAGE; REPAIR;
ACCESSIBILITY
AB The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo. Here, we demonstrate that RAG protein binding occurs in a highly focal manner to a small region of active chromatin encompassing Ig kappa and Tcr alpha J gene segments and Igh and Tcr beta J and J-proximal D gene segments. Formation of these small RAG-bound regions, which we refer to as recombination centers, occurs in a developmental stage- and lineage-specific manner. Each RAG protein is independently capable of specific binding within recombination centers. While RAG1 binding was detected only at regions containing recombination signal sequences, RAG2 binds at thousands of sites in the genome containing histone 3 trimethylated at lysine 4. We propose that recombination centers coordinate V(D)J recombination by providing discrete sites within which gene segments are captured for recombination.
C1 [Resch, Wolfgang; Yamane, Arito; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Ji, Yanhong; Corbett, Elizabeth; Schatz, David G.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
[Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Corbett, Elizabeth; Schatz, David G.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Casellas, R (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM casellar@mail.nih.gov; david.schatz@yale.edu
RI Yamane, Arito/A-2959-2013; Schatz, David/A-6748-2013
OI Schatz, David/0000-0002-5669-1176
FU Public Health Service [AI32524]; National Institutes of Health
FX The authors thank S. Desiderio, R. Sen, and R. Subrahmanyam for
lentiviral vectors expressing WT and W453A RAG2, M. Nussenzweig for
providing the HG BAC, B. Sleckman and A. Bredemeyer for providing cell
lines and technical advice, S. Zhou for help with the analysis of mice,
J. Duke for analysis of genome-wide H3K4me3 data, the Yale Transgenic
Mouse Service for generating transgenic mice, members of the Schatz lab
for helpful discussions, the Yale Immunobiology Cell Sorting Facility
for cell sorting, and M. Krangel, M. Schlissel, and B. Sleckman for
critical reading of the manuscript. This work was supported in part by
Public Health Service grant AI32524 to D. G. S. and in part by the
Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health.
D.G.S. is an investigator of the Howard Hughes Medical Institute.
NR 50
TC 141
Z9 142
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD APR 30
PY 2010
VL 141
IS 3
BP 419
EP 431
DI 10.1016/j.cell.2010.03.010
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 589UX
UT WOS:000277180800014
PM 20398922
ER
PT J
AU Mazars, R
Gonzalez-De-Peredo, A
Cayrol, C
Lavigne, AC
Vogel, JL
Ortega, N
Lacroix, C
Gautier, V
Huet, G
Ray, A
Monsarrat, B
Kristie, TM
Girard, JP
AF Mazars, Raoul
Gonzalez-de-Peredo, Anne
Cayrol, Corinne
Lavigne, Anne-Claire
Vogel, Jodi L.
Ortega, Nathalie
Lacroix, Chrystelle
Gautier, Violette
Huet, Gaelle
Ray, Aurelie
Monsarrat, Bernard
Kristie, Thomas M.
Girard, Jean-Philippe
TI The THAP-Zinc Finger Protein THAP1 Associates with Coactivator HCF-1 and
O-GlcNAc Transferase A LINK BETWEEN DYT6 AND DYT3 DYSTONIAS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LINKED DYSTONIA-PARKINSONISM; CELL-PROLIFERATION; TORSION DYSTONIA;
GENE; EXPRESSION; PROMOTERS; MODULE; DOMAIN; VP16
AB THAP1 is a sequence-specific DNA binding factor that regulates cell proliferation through modulation of target genes such as the cell cycle-specific gene RRM1. Mutations in the THAP1 DNA binding domain, an atypical zinc finger (THAP-zf), have recently been found to cause DYT6 dystonia, a neurological disease characterized by twisting movements and abnormal postures. In this study, we report that THAP1 shares sequence characteristics, in vivo expression patterns and protein partners with THAP3, another THAP-zf protein. Proteomic analyses identified HCF-1, a potent transcriptional coactivator and cell cycle regulator, and O-GlcNAc transferase (OGT), the enzyme that catalyzes the addition of O-GlcNAc, as major cellular partners of THAP3. THAP3 interacts with HCF-1 through a consensus HCF-1-binding motif (HBM), a motif that is also present in THAP1. Accordingly, THAP1 was found to bind HCF-1 in vitro and to associate with HCF-1 and OGT in vivo. THAP1 and THAP3 belong to a large family of HCF-1 binding factors since seven other members of the human THAP-zf protein family were identified, which harbor evolutionary conserved HBMs and bind to HCF-1. Chromatin immunoprecipitation (ChIP) assays and RNA interference experiments showed that endogenous THAP1 mediates the recruitment of HCF-1 to the RRM1 promoter during endothelial cell proliferation and that HCF-1 is essential for transcriptional activation of RRM1. Together, our findings suggest HCF-1 is an important cofactor for THAP1. Interestingly, our results also provide an unexpected link between DYT6 and DYT3 (X-linked dystonia-parkinsonism) dystonias because the gene encoding the THAP1/DYT6 protein partner OGT maps within the DYT3 critical region on Xq13.1.
C1 [Mazars, Raoul; Gonzalez-de-Peredo, Anne; Cayrol, Corinne; Lavigne, Anne-Claire; Ortega, Nathalie; Lacroix, Chrystelle; Gautier, Violette; Huet, Gaelle; Ray, Aurelie; Monsarrat, Bernard; Girard, Jean-Philippe] CNRS, IPBS, F-31077 Toulouse, France.
[Mazars, Raoul; Gonzalez-de-Peredo, Anne; Cayrol, Corinne; Lavigne, Anne-Claire; Ortega, Nathalie; Lacroix, Chrystelle; Gautier, Violette; Huet, Gaelle; Ray, Aurelie; Monsarrat, Bernard; Girard, Jean-Philippe] Univ Toulouse, UPS, IPBS, F-31077 Toulouse, France.
[Vogel, Jodi L.; Kristie, Thomas M.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Girard, JP (reprint author), CNRS, IPBS, 205 Route Narbonne, F-31077 Toulouse, France.
EM Jean-Philippe.Girard@ipbs.fr
RI CAYROL, Corinne/C-2106-2011; GIRARD, Jean-Philippe/F-5229-2010
FU Ligue Nationale contre le Cancer; INCA; ANR; National Institutes of
Health, Laboratory of Viral Diseases, NIAID
FX The work was supported by grants from Ligue Nationale contre le Cancer
(Equipe labellise e Ligue 2009), INCA, and ANR-Programme Blanc
"Regulome." This work was also supported, in part, by the Intramural
Research Program of the National Institutes of Health, Laboratory of
Viral Diseases, NIAID.
NR 27
TC 44
Z9 51
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 30
PY 2010
VL 285
IS 18
BP 13364
EP 13371
DI 10.1074/jbc.M109.072579
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 587JL
UT WOS:000276987700007
PM 20200153
ER
PT J
AU Xia, GQ
Maier, L
Sanchez-Carballo, P
Li, M
Otto, M
Holst, O
Peschel, A
AF Xia, Guoqing
Maier, Lisa
Sanchez-Carballo, Patricia
Li, Min
Otto, Michael
Holst, Otto
Peschel, Andreas
TI Glycosylation of Wall Teichoic Acid in Staphylococcus aureus by TarM
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-ACETYLGLUCOSAMINYLRIBITOL LINKAGES; BACTERIOPHAGE-RESISTANT MUTANTS;
IN-VITRO RECONSTITUTION; BACILLUS-SUBTILIS 168; CELL-WALL;
LISTERIA-MONOCYTOGENES; ENZYMATIC SYNTHESIS; STREPTOCOCCUS-PNEUMONIAE;
NASAL COLONIZATION; GLYCEROL PHOSPHATE
AB Wall teichoic acid (WTA) glycopolymers are major constituents of cell envelopes in Staphylococcus aureus and related Gram-positive bacteria with important roles in cell wall maintenance, susceptibility to antimicrobial molecules, biofilm formation, and host interaction. Most S. aureus strains express polyribitol phosphate WTA substituted with D-alanine and N-acetylglucosamine (GlcNAc). WTA sugar modifications are highly variable and have been implicated in bacteriophage susceptibility and immunogenicity, but the pathway and enzymes of staphylococcal WTA glycosylation have remained unknown. Revisiting the structure of S. aureus RN4220 WTA by NMR analysis revealed the presence of canonical polyribitol phosphate WTA bearing only alpha-linked GlcNAc substituents. A RN4220 transposon mutant resistant to WTA-dependent phages was identified and shown to produce altered WTA, which exhibited faster electrophoretic migration and lacked completely the WTA alpha-GlcNAc residues. Disruption of a gene of unknown function, renamed tarM, was responsible for this phenotype. Recombinant TarM was capable of glycosylating WTA in vitro in a UDP-GlcNAc-dependent manner, thereby confirming its WTA GlcNAc-transferase activity. Deletion of the last seven amino acids from the C terminus abolished the activity of TarM. tarM-related genes were found in the genomes of several WTA-producing bacteria, suggesting that TarM-mediated WTA glycosylation is a general pathway in Gram-positive bacteria. Our study represents a basis for dissecting the biosynthesis and function of glycosylated WTA in S. aureus and other bacteria.
C1 [Xia, Guoqing; Maier, Lisa; Peschel, Andreas] Univ Tubingen, Div Cellular & Mol Microbiol, Interfac Inst Microbiol & Infect Med, D-72076 Tubingen, Germany.
[Sanchez-Carballo, Patricia; Holst, Otto] Leibniz Ctr Med & Biosci, Div Struct Biochem, Res Ctr Borstel, D-23845 Borstel, Germany.
[Li, Min; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Peschel, A (reprint author), Univ Tubingen, Div Cellular & Mol Microbiol, Interfac Inst Microbiol & Infect Med, Elfriede Aulhorn Str 6, D-72076 Tubingen, Germany.
EM andreas.peschel@uni-tuebingen.de
RI Xia, Guoqing/C-2365-2015;
OI Xia, Guoqing/0000-0003-4492-9156; Otto, Michael/0000-0002-2222-4115
FU German Research Foundation [SFB34, SFB766, GKR685]; German Ministry of
Education and Technology; National Institutes of Health [AI000904-08]
FX This work was supported by German Research Foundation Grants TR-SFB34,
SFB766, and GKR685 and by the German Ministry of Education and
Technology (SkinStaph) (to A. P.) and also in part by the National
Institutes of Health Intramural Research Program of NIAIDZIA AI000904-08
(to M. L. and M. O.).
NR 58
TC 52
Z9 52
U1 1
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 30
PY 2010
VL 285
IS 18
BP 13405
EP 13415
DI 10.1074/jbc.M109.096172
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 587JL
UT WOS:000276987700012
PM 20185825
ER
PT J
AU Miriyala, S
Subramanian, T
Panchatcharam, M
Ren, HM
McDermott, MI
Sunkara, M
Drennan, T
Smyth, SS
Spielmann, HP
Morris, AJ
AF Miriyala, Sumitra
Subramanian, Thangaiah
Panchatcharam, Manikandan
Ren, Hongmei
McDermott, Mark I.
Sunkara, Manjula
Drennan, Tracy
Smyth, Susan S.
Spielmann, H. Peter
Morris, Andrew J.
TI Functional Characterization of the Atypical Integral Membrane Lipid
Phosphatase PDP1/PPAPDC2 Identifies a Pathway for Interconversion of
Isoprenols and Isoprenoid Phosphates in Mammalian Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PRESQUALENE DIPHOSPHATE PHOSPHATASE; LYSOPHOSPHATIDIC ACID; RHO GTPASES;
PROTEIN; FARNESYL; BIOSYNTHESIS; CHOLESTEROL; ACTIVATION; MECHANISMS;
INHIBITOR
AB The polyisoprenoid diphosphates farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are intermediates in the synthesis of cholesterol and related sterols by the mevalonate pathway and precursors for the addition of isoprenyl anchors to many membrane proteins. We developed tandem mass spectrometry assays to evaluate polyisoprenoid diphosphate phosphatase activity of an unusual integral membrane lipid enzyme: type 1 polyisoprenoid diphosphate phosphatase encoded by the PPAPDC2 gene (PDP1/PPAPDC2). In vitro, recombinant PDP1/PPAPDC2 preferentially hydrolyzed polyisoprenoid diphosphates, including FPP and GGPP over a variety of glycerol-and sphingo-phospholipid substrates. Overexpression of mammalian PDP1/PPAPDC2 in budding yeast depletes cellular pools of FPP leading to growth defects and sterol auxotrophy. In mammalian cells, PDP1/PPAPDC2 localizes to the endoplasmic reticulum and nuclear envelope and, unlike the structurally related lipid phosphate phosphatases, is predicted to be oriented with key residues of its catalytic domain facing the cytoplasmic face of the membrane. Studies using synthetic isoprenols with chemical properties that facilitate detection by mass spectrometry identify a pathway for interconversion of isoprenols and isoprenoid diphosphates in intact mammalian cells and demonstrate a role for PDP1/PPAPDC2 in this process. Overexpression of PDP1/PPAPDC2 in mammalian cells substantially decreases protein isoprenylation and results in defects in cell growth and cytoskeletal organization that are associated with dysregulation of Rho family GTPases. Taken together, these results focus attention on integral membrane lipid phosphatases as regulators of isoprenoid phosphate metabolism and suggest that PDP1/PPAPDC2 is a functional isoprenoid diphosphate phosphatase.
C1 [Miriyala, Sumitra; Panchatcharam, Manikandan; Ren, Hongmei; Sunkara, Manjula; Drennan, Tracy; Smyth, Susan S.; Spielmann, H. Peter; Morris, Andrew J.] Univ Kentucky, Div Cardiovasc Med, Gill Heart Inst, Lexington, KY 40536 USA.
[Subramanian, Thangaiah; Morris, Andrew J.] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
[Spielmann, H. Peter] Univ Kentucky, Dept Chem, Lexington, KY 40536 USA.
[Spielmann, H. Peter] Univ Kentucky, Struct Biol Ctr, Lexington, KY 40536 USA.
[Smyth, Susan S.] Dept Vet Affairs Med Ctr, Lexington, KY 40511 USA.
[McDermott, Mark I.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Morris, AJ (reprint author), Univ Kentucky, Div Cardiovasc Med, Gill Heart Inst, 900 S Limestone St,326 CTW Bldg, Lexington, KY 40536 USA.
EM a.j.morris@uky.edu
RI Morris, Andrew/B-7869-2010; Thangaiah, Subramanian/H-3824-2011;
OI sunkara, Manjula/0000-0001-6151-1929
FU National Institutes of Health [5R01GM050388, P20RR001954, 5R01GM066152];
Lexington VA Medical Center
FX This work was supported, in whole or in part, by National Institutes of
Health Grants 5R01GM050388, P20RR001954, and 5R01GM066152 (to A.J.M., H.
P. S., and S. S. S.). This study is the result of work supported with
resources and the use of facilities at the Lexington VA Medical Center.
NR 45
TC 11
Z9 11
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 30
PY 2010
VL 285
IS 18
BP 13918
EP 13929
DI 10.1074/jbc.M109.083931
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 587JL
UT WOS:000276987700066
PM 20110354
ER
PT J
AU Tong, SQ
Yan, JZ
Guan, YX
Fu, YE
Ito, Y
AF Tong, Shengqiang
Yan, Jizhong
Guan, Yi-Xin
Fu, Yaner
Ito, Yoichiro
TI Separation of alpha-cyclohexylmandelic acid enantiomers using biphasic
chiral recognition high-speed counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Chiral separation; High-speed counter-current; chromatography; Biphasic
chiral recognition; alpha-Cyclohexylmandelic acid; Optical activity
ID CENTRIFUGAL PARTITION CHROMATOGRAPHY; LIQUID-CHROMATOGRAPHY; STATIONARY
PHASES; SELECTORS; ENANTIOSEPARATION; DERIVATIVES; RESOLUTION;
OPTIMIZATION; EXTRACTION; CELLULOSE
AB This work concentrates on a chiral separation technology named biphasic recognition applied to resolution of alpha-cyclohexylmandelic acid enantiomers by high-speed counter-current chromatography (HSCCC). The biphasic chiral recognition HSCCC was performed by adding lipophilic(-)-2-ethylhexyl tartrate in the organic stationary phase and hydrophilic hydroxypropyl-beta-cyclodextrin in the aqueous mobile phase, which preferentially recognized the (-)-enantiomer and (+)-enantiomer, respectively. The two-phase solvent system composed of n-hexane-methyl tert-butyl ether-water (9:1:10, v/v/v) with the above chiral selectors was selected according to the partition coefficient and separation factor of the target enantiomers. Important parameters involved in the chiral separation were investigated, namely the types of the chiral selectors (CS); the concentration of each chiral selector; pH of the mobile phase and the separation temperature. The mechanism involved in this biphasic recognition chiral separation by HSCCC was discussed. Langmuirian isotherm was employed to estimate the loading limits for a given value of chiral selectors. Under optimum separation conditions, 3.5-22.0 mg of alpha-cyclohexylmandelic acid racemate were separated using the analytical apparatus and 440 mg of racemate was separated using the preparative one. The purities of both of the fractions including (+)-enantiomer and (-)-enantiomer from the preparative CCC separation were over 99.5% determined by HPLC and enantiomeric excess reached 100% for the (+/-)-enantiomers. Recovery for the target compounds from the CCC fractions reached 85-88% yielding 186 mg of (+)-enantiomer and 190 mg of (-)-enantiomer. The overall experimental results show that the HSCCC separation of enantiomer based on biphasic recognition, in which only if the CSs involved will show affinity for opposite enantiomers of the analyte, is much more efficient than the traditional monophasic recognition chiral separation, since it utilizes the cooperation of both of lipophilic and hydrophilic chiral selectors. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Tong, Shengqiang; Yan, Jizhong; Fu, Yaner] Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Zhejiang, Peoples R China.
[Tong, Shengqiang; Guan, Yi-Xin] Zhejiang Univ, Dept Biol & Chem Engn, Hangzhou 310027, Peoples R China.
[Fu, Yaner] Zhejiang Huahai Pharmaceut Co Ltd, Qual Control Dept, Taizhou 317024, Peoples R China.
[Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
RP Yan, JZ (reprint author), Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Zhejiang, Peoples R China.
EM zyx@zjut.edu.cn; guanyx@zju.edu.cn
RI yan, jizhong/G-9922-2012
FU Department of Education of Zhejiang Province [Y200803791]; Natural
Science Foundation of Zhejiang Province of PR China [Y406429]
FX This work was financially supported by Department of Education of
Zhejiang Province (Y200803791) and Natural Science Foundation of
Zhejiang Province of PR China (Y406429).
NR 21
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD APR 30
PY 2010
VL 1217
IS 18
BP 3044
EP 3052
DI 10.1016/j.chroma.2010.02.077
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 592JC
UT WOS:000277373800006
PM 20303497
ER
PT J
AU Yang, Y
Gu, DY
Aisa, HA
Ito, Y
AF Yang, Yi
Gu, Dongyu
Aisa, Haji Akber
Ito, Yoichiro
TI Evaluation of the effect of column orientation in type-I high-speed
counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Type-I counter-current chromatography; Coil planet centrifuge; The angle
against the rotating centrifugal; force field; Retention of the
stationary phase; Resolution; Dipeptide; DNP-amino acid
ID COIL PLANET CENTRIFUGE
AB The performance of type-I high-speed counter-current chromatography was evaluated by changing the column inclination against the rotating centrifugal force field. The separations were performed with two different solvent systems composed of 1-butanol-acetic acid-water (4.75:0.25:5, v/v) (BAW) and hexane-ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMW) using dipeptides and DNP-amino acid as test samples, respectively. A set of short coiled columns connected in series is mounted around the holder hub in two different ways: in the parallel orientation, all column units are arranged in parallel to each other and mounted on the holder at various angles against the horizontal plane. In the zigzag configuration, the neighboring units of the same column are mounted symmetrically forming various angles apart. In the parallel configuration, for both the BAW and HEMW systems, Sf (the retention of stationary phase) first increased as the column angle decreased from 90 degrees to 60 degrees and then decreased, as the column angle further decreased from 60 degrees to 0 degrees, while Rs (peak resolution) continually declined over the entire column angle range from 90 degrees to 0 degrees. But, for both solvent systems, with the zigzag configuration, retention of stationary phase and resolution both decreased as the column angle decreased from 90 degrees to 0 degrees. In general, Sf and Rs for separation of dipeptides in the BAW system, from 90 degrees to 15 degrees, is better for the parallel orientation than for the zigzag configuration. However, at 0 degrees, Sf and Rs are better for the zigzag orientation. In the DNP-amino acid separation with the HEMW system, retention of the stationary phase and Rs for the parallel orientation is better than that for the zigzag orientation from 90 degrees to 30 degrees, whereas from 30 degrees to 0 degrees the results are opposite. Over all results of our studies revealed that the formally used column orientation [5] at 90 degrees inclination yields the highest peak resolution in both solvent systems. Published by Elsevier B.V.
C1 [Yang, Yi; Gu, Dongyu; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Yang, Yi; Gu, Dongyu; Aisa, Haji Akber] Chinese Acad Sci, Key Lab Chem Plant Resources Arid Reg, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Drive,Bldg 10,Room 8N230, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU Intramural NIH HHS [ZIA HL006022-01]
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U1 0
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD APR 30
PY 2010
VL 1217
IS 18
BP 3167
EP 3170
DI 10.1016/j.chroma.2010.03.004
PG 4
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 592JC
UT WOS:000277373800020
PM 20346457
ER
PT J
AU Mbisa, GL
Miley, W
Gamache, CJ
Gillette, WK
Esposito, D
Hopkins, R
Busch, MP
Schreiber, GB
Little, RF
Yarchoan, R
Ortiz-Conde, BA
Labo, N
Whitby, D
AF Mbisa, Georgina L.
Miley, Wendell
Gamache, Christine J.
Gillette, William K.
Esposito, Dominic
Hopkins, Ralph
Busch, Michael P.
Schreiber, George B.
Little, Richard F.
Yarchoan, Robert
Ortiz-Conde, Betty A.
Labo, Nazzarena
Whitby, Denise
TI Detection of antibodies to Kaposi's sarcoma-associated herpesvirus: A
new approach using K8.1 ELISA and a newly developed recombinant LANA
ELISA
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE KSHV serology; ELISA; LANA; K8.1
ID LATENT CLASS ANALYSIS; READING FRAME K8.1; NUCLEAR ANTIGEN;
DNA-SEQUENCES; MONOCLONAL-ANTIBODIES; GENERAL-POPULATION; SEROLOGIC
ASSAYS; HUMAN-HERPESVIRUS-8; INFECTION; IDENTIFICATION
AB Detection of antibodies to Kaposi's sarcoma-associated herpesvirus (KSHV or Human herpesvirus 8) is a topic of ongoing controversy. KSHV expresses multiple antigens and host responses are highly variable. We have previously described an algorithm for determining KSHV infection based on K8.1 ELISA and LANA immunofluorescence assay (IFA). Here we describe the development of a recombinant ELISA for LANA and an improved testing strategy using ELISAs for LANA and K8.1. We assessed mammalian and baculovirus expression systems for the production of full-length recombinant LANA. We evaluated the performance of LANA ELISAs using human serum samples from several sources including blood donors and clinical patients diagnosed with Kaposi's sarcoma and compared them to LANA IFA. Both LANA ELISAs exhibited comparable sensitivity and specificity to LANA IFA but showed considerably greater reliability. The LANA ELISA can thus be used in conjunction with the previously described K8.1 ELISA to enable the highly sensitive and specific detection of antibodies to KSHV. Use of this testing strategy will provide a more accurate and reliable diagnostic assessment of KSHV status. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Mbisa, Georgina L.; Gamache, Christine J.; Ortiz-Conde, Betty A.] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Mbisa, Georgina L.; Gamache, Christine J.; Ortiz-Conde, Betty A.] NCI, Viral Technol Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Gillette, William K.; Esposito, Dominic; Hopkins, Ralph; Ortiz-Conde, Betty A.] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Schreiber, George B.] Westat Corp, Rockville, MD 20850 USA.
[Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Whitby, D (reprint author), NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM Denise.Whitby@nih.gov
RI Labo, Nazzarena/H-8655-2012
OI Labo, Nazzarena/0000-0001-5953-4064
FU National Cancer Institute, National Institutes of Health [N01-CO-12400]
FX We thank Thomas Schulz of The University of Hanover for providing the KS
lesion clone and Sabine Geisse of Novartis for the EBNA Origin
Destination vectors. We also thank Deborah Todd of Westat, Inc. and
Kathleen Wyvil and Karen Aleman of the National Cancer Institute's HIV
and AIDS Malignancy Branch. We are grateful to the National Heart, Lung
and Blood Institute for establishing and providing the Human Herpes
Virus 8 (HHV-8) Special Collection from the Institute's Retrovirus
Epidemiology Donor Study (REDS) General Leukocyte/Plasma Repository
(GLPR), https://biolincc.nhlbi.nih.gov/studies/hhv8/?q=reds. This
project has been funded in whole or in part with funds from the National
Cancer Institute, National Institutes of Health, under contract
N01-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government
NR 27
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD APR 30
PY 2010
VL 356
IS 1-2
BP 39
EP 46
DI 10.1016/j.jim.2010.02.015
PG 8
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 599OY
UT WOS:000277924200005
PM 20211626
ER
PT J
AU Huang, XM
Auinger, P
Eberly, S
Oakes, D
Schwarzschild, M
Ascherio, A
Mailman, R
Chen, HL
AF Huang, Xuemei
Auinger, Peggy
Eberly, Shirley
Oakes, David
Schwarzschild, Michael
Ascherio, Alberto
Mailman, Richard
Chen, Honglei
CA Parkinson Study Grp DATATOP Invest
TI Serum Cholesterol as a Predictor of the Rate of Clinical Decline in
Parkinson Disease: Results from DATATOP.
SO MOVEMENT DISORDERS
LA English
DT Meeting Abstract
CT 24th Annual Symposium on Etiology, Pathogenesis and Treatment of
Parkinson's Disease and Other Movement Disorders
CY MAY 15, 2010
CL Irving, TX
C1 [Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA.
[Auinger, Peggy] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA.
[Eberly, Shirley; Oakes, David] Univ Rochester, Dept Biostat, Rochester, NY USA.
[Schwarzschild, Michael] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Nutr, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Epidemiol, Boston, MA 02115 USA.
[Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
NR 0
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U1 0
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR 30
PY 2010
VL 25
IS 6
BP II
EP II
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 591OS
UT WOS:000277311500035
ER
PT J
AU Kranick, SM
Mowry, EM
Colcher, A
Horn, S
Golbe, LI
AF Kranick, Sarah M.
Mowry, Ellen M.
Colcher, Amy
Horn, Stacy
Golbe, Lawrence I.
TI Movement Disorders and Pregnancy: A Review of the Literature
SO MOVEMENT DISORDERS
LA English
DT Review
DE Parkinson's disease; pregnancy; teratogenicity; Wilson's disease; chorea
gravidarum
ID RESTLESS LEGS SYNDROME; PARKINSONS-DISEASE; WILSONS-DISEASE;
HUNTINGTONS-DISEASE; CHOREA GRAVIDARUM; FRIEDREICHS-ATAXIA; THERAPY;
LEVODOPA; PATIENT; WOMEN
AB Pregnant patients are rarely encountered in the movement disorders clinic, but they present significant dilemmas regarding treatment and counseling for neurologists. While movement disorders in pregnancy once described those disorders arising de novo during pregnancy, such as chorea gravidarum or restless leg syndrome, advancing maternal age in Western countries will likely increase the number of women in whom pregnancy complicates a pre-existing movement disorder. Physicians treating these women must be aware of the impact of the movement disorder and its treatment on fertility, pregnancy, fetal development, lactation, and infant care. This review summarizes retrospective series and case reports to both guide clinicians and to stimulate and direct the design of prospective studies. (C) 2010 Movement Disorder Society
C1 [Kranick, Sarah M.; Colcher, Amy; Horn, Stacy] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Mowry, Ellen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Golbe, Lawrence I.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA.
RP Kranick, SM (reprint author), NINDS, NIH, Human Motor Control Sect, Bldg 10-7D42,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM sarah.kranick@nih.gov
NR 65
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U1 2
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR 30
PY 2010
VL 25
IS 6
BP 665
EP 671
DI 10.1002/mds.23071
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 591OS
UT WOS:000277311500001
PM 20437535
ER
PT J
AU van de Leemput, J
Wavrant-De Vrieze, F
Rafferty, I
Bras, JM
Giunti, P
Fisher, EMC
Hardy, JA
Singleton, AB
Houlden, H
AF van de Leemput, Joyce
Wavrant-De Vrieze, Fabienne
Rafferty, Ian
Bras, Jose M.
Giunti, Paola
Fisher, Elizabeth M. C.
Hardy, John A.
Singleton, Andrew B.
Houlden, Henry
TI Sequencing Analysis of the ITPR1 Gene in a Pure Autosomal Dominant
Spinocerebellar Ataxia Series
SO MOVEMENT DISORDERS
LA English
DT Article
DE ataxia; spinocerebellar; SCA15; genetics; inositol-1,4,5-triphosphate
receptor type 1
ID DELETION; SCA15
AB Spinocerebellar ataxia type 15 and 16 (SCA15/16) are autosomal dominant cerebellar ataxias that are slowly progressive with a predominantly pure ataxia phenotype (ADCA III). The locus for SCA15 was first mapped to 3p24.2-3pter and subsequently full or partial deletions in the inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene were identified in several ADCA III families that segregated with the disease. A single missense coding variant has been described, but the pathogenicity of this change has not been proven. We sequenced the entire coding region and flanking regions of ITPR1 in unrelated ADCA III families (n = 38) that were negative for large deletions on whole genome arrays, and for which SCAs 1, 2, 3, 6, 7, 8, 11, 12, 14, 17 and the Friedreich's ataxia expansion were excluded in all probands. Mutation at SCA5, 10, and 27 was also excluded in some families. A number of coding and noncoding polymorphisms were identified but no ITPR1 mutations were found. The results indicate that point mutations in ITPR1 are at best a rare cause of ADCA III. (C) 2010 Movement Disorder Society
C1 [van de Leemput, Joyce; Wavrant-De Vrieze, Fabienne; Rafferty, Ian; Bras, Jose M.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[van de Leemput, Joyce; Giunti, Paola; Hardy, John A.; Houlden, Henry] UCL, Inst Neurol, Reta Lila Weston Labs, Dept Mol Neurosci, London, England.
[van de Leemput, Joyce; Fisher, Elizabeth M. C.] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Bras, Jose/A-1428-2011; Singleton, Andrew/C-3010-2009; Hardy,
John/C-2451-2009; Giunti, Paola /E-5526-2012; Houlden,
Henry/C-1532-2008;
OI Giunti, Paola /0000-0003-3508-4788; Houlden, Henry/0000-0002-2866-7777;
Bras, Jose/0000-0001-8186-0333
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [Z01 AG000957-06]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; project number Z01 AG000957-06.
DNA panels from the NINDS Human Genetics Resource Center DNA and Cell
Line Repository (http://ccr.coriell.org/ninds) were used in this study.
The submitters that contributed samples are acknowledged in detailed
descriptions of each panel: (NDPT019, NDPT020, NDPT022, NDPT023,
NDPT024).
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U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR 30
PY 2010
VL 25
IS 6
BP 771
EP 773
DI 10.1002/mds.22970
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 591OS
UT WOS:000277311500017
PM 20437544
ER
PT J
AU Velma, V
Tchounwou, PB
AF Velma, Venkatramreddy
Tchounwou, Paul B.
TI Chromium-induced biochemical, genotoxic and histopathologic effects in
liver and kidney of goldfish, carassius auratus
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Hexavalent chromium; acute exposure; goldfish; oxidative stress;
genotoxicity; histopathology
ID RAINBOW-TROUT; LIPID-PEROXIDATION; OXIDATIVE STRESS; DNA-DAMAGE;
HEXAVALENT CHROMIUM; SPECTROPHOTOMETRIC METHOD; CHANNA-PUNCTATUS;
SALMO-GAIRDNERI; GENE-EXPRESSION; STRAND BREAKS
AB Fish constitute an excellent model to understand the mechanistic aspects of metal toxicity vis-a-vis oxidative stress in aquatic ecosystems. Hexavalent chromium (Cr (VI)), clue to its redox potential can induce oxidative stress (OS) in fish and impair their health. In the present investigation, we hypothesize that OS plays a key role in chromium induced toxicity in goldfish: leading to the production of reactive oxygen species (ROS) such as O-2 H2O2, OH, and subsequent modulation of the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), metallothioneins (MT), glutathione proxidase (GPx), genotoxicity and histopathology. To test this hypothesis, antioxidant enzymes. DNA damage and histopathology assays were performed in liver and kidney tissues of goldfish exposed to different concentrations of Cr (VI) (LC12.5. LC25 and LC50) following 96 h static renewal bioassay. The results of this study clearly show that the fish experienced OS as characterized by significant modulation of enzyme activities, induction of DNA damage and microscopic morphological changes in the liver and kidney. In both tissues, CAT activity was decreased whereas SOD activity and hydroperoxide levels were increased. In addition, GPx activity also increased significantly in higher test concentrations, especially in the kidney. MT induction and DNA damage were observed in both tissues in a concentration dependent manner. Microscopic examination of organ morphology indicated degeneration of liver tissue and necrosis of central vein. Necrosis of kidney tubular epithelial cells and tubules was observed at higher Cr (VI) concentrations. Taking together the findings of this study are helpful in organ-specific risk assessment of Cr (VI)-induced oxidative stress, genotoxicity and histopathology in fish. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Velma, Venkatramreddy; Tchounwou, Paul B.] Jackson State Univ, Environm Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Environm Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
RI Abdel-Gawad, Fagr/F-8442-2011; K, Raghavan/G-7737-2016
OI Abdel-Gawad, Fagr/0000-0002-6755-3211; K, Raghavan/0000-0003-3404-5082
FU NIH-RCMI [5G12RR013459]; NOAA-ECSC [NA06060AR4810164, 000953]
FX This research was supported in by the NIH-RCMI Grant No. 5G12RR013459,
and in part by a grant from the NOAA-ECSC Grant No. NA06060AR4810164 &
Subcontract No. 000953.
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U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD APR 30
PY 2010
VL 698
IS 1-2
BP 43
EP 51
DI 10.1016/j.mrgentox.2010.03.014
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 605BE
UT WOS:000278321500008
PM 20348018
ER
PT J
AU Bumb, A
Regino, CAS
Perkins, MR
Bernardo, M
Ogawa, M
Fugger, L
Choyke, PL
Dobson, PJ
Brechbiel, MW
AF Bumb, A.
Regino, C. A. S.
Perkins, M. R.
Bernardo, M.
Ogawa, M.
Fugger, L.
Choyke, P. L.
Dobson, P. J.
Brechbiel, M. W.
TI Preparation and characterization of a magnetic and optical dual-modality
molecular probe
SO NANOTECHNOLOGY
LA English
DT Article
ID SILICA NANOPARTICLES; PARTICLES; CELLS; ENCAPSULATION; TOXICITY; SYSTEMS
AB Multi-modality imaging probes combine the advantages of individual imaging techniques to yield highly detailed anatomic and molecular information in living organisms. Herein, we report the synthesis and characterization of a dual-modality nanoprobe that couples the magnetic properties of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with the near infrared fluorescence of Cy5.5. The fluorophore is encapsulated in a biocompatible shell of silica surrounding the iron oxide core for a final diameter of similar to 17 nm. This silica-coated iron oxide nanoparticle (SCION) has been analyzed by transmission electron microscopy, dynamic light scattering, and superconducting quantum interference device (SQUID). The particle demonstrates a strong negative surface charge and maintains colloidal stability in the physiological pH range. Magnetic hysteresis analysis confirms superparamagnetic properties that could be manipulated for thermotherapy. The viability of primary human monocytes, T cells, and B cells incubated with the particle has been examined in vitro. In vivo analysis of agent leakage into subcutaneous A431 tumors in mice was also conducted. This particle has been designed for diagnostic application with magnetic resonance and fluorescence imaging, and has future potential to serve as a heat-sensitive targeted drug delivery platform.
C1 [Bumb, A.; Brechbiel, M. W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Regino, C. A. S.; Ogawa, M.; Choyke, P. L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Perkins, M. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Perkins, M. R.; Fugger, L.] Univ Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
[Bernardo, M.] NCI Frederick, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Dobson, P. J.] Univ Oxford, Kidlington OX5 1PF, Oxon, England.
RP Bumb, A (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room 1B53,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Bumba@mail.nih.gov; martinwb@mail.nih.gov
FU Marshall Commission; NIH, National Cancer Institute, Center for Cancer
Research
FX We would like to thank Wei Lui and Yuxi Pang for providing the
relaxation mapping tool. This research was supported by the Marshall
Commission and the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research.
NR 35
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Z9 22
U1 7
U2 23
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
J9 NANOTECHNOLOGY
JI Nanotechnology
PD APR 30
PY 2010
VL 21
IS 17
AR 175704
DI 10.1088/0957-4484/21/17/175704
PG 9
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 583JP
UT WOS:000276671300019
PM 20368682
ER
PT J
AU Hellsten, U
Harland, RM
Gilchrist, MJ
Hendrix, D
Jurka, J
Kapitonov, V
Ovcharenko, I
Putnam, NH
Shu, SQ
Taher, L
Blitz, IL
Blumberg, B
Dichmann, DS
Dubchak, I
Amaya, E
Detter, JC
Fletcher, R
Gerhard, DS
Goodstein, D
Graves, T
Grigoriev, IV
Grimwood, J
Kawashima, T
Lindquist, E
Lucas, SM
Mead, PE
Mitros, T
Ogino, H
Ohta, Y
Poliakov, AV
Pollet, N
Robert, J
Salamov, A
Sater, AK
Schmutz, J
Terry, A
Vize, PD
Warren, WC
Wells, D
Wills, A
Wilson, RK
Zimmerman, LB
Zorn, AM
Grainger, R
Grammer, T
Khokha, MK
Richardson, PM
Rokhsar, DS
AF Hellsten, Uffe
Harland, Richard M.
Gilchrist, Michael J.
Hendrix, David
Jurka, Jerzy
Kapitonov, Vladimir
Ovcharenko, Ivan
Putnam, Nicholas H.
Shu, Shengqiang
Taher, Leila
Blitz, Ira L.
Blumberg, Bruce
Dichmann, Darwin S.
Dubchak, Inna
Amaya, Enrique
Detter, John C.
Fletcher, Russell
Gerhard, Daniela S.
Goodstein, David
Graves, Tina
Grigoriev, Igor V.
Grimwood, Jane
Kawashima, Takeshi
Lindquist, Erika
Lucas, Susan M.
Mead, Paul E.
Mitros, Therese
Ogino, Hajime
Ohta, Yuko
Poliakov, Alexander V.
Pollet, Nicolas
Robert, Jacques
Salamov, Asaf
Sater, Amy K.
Schmutz, Jeremy
Terry, Astrid
Vize, Peter D.
Warren, Wesley C.
Wells, Dan
Wills, Andrea
Wilson, Richard K.
Zimmerman, Lyle B.
Zorn, Aaron M.
Grainger, Robert
Grammer, Timothy
Khokha, Mustafa K.
Richardson, Paul M.
Rokhsar, Daniel S.
TI The Genome of the Western Clawed Frog Xenopus tropicalis
SO SCIENCE
LA English
DT Article
ID MOLECULAR PALEONTOLOGY; TRANSPOSABLE ELEMENTS; IMMUNE-SYSTEM; GENE;
SEQUENCE; IGD
AB The western clawed frog Xenopus tropicalis is an important model for vertebrate development that combines experimental advantages of the African clawed frog Xenopus laevis with more tractable genetics. Here we present a draft genome sequence assembly of X. tropicalis. This genome encodes more than 20,000 protein-coding genes, including orthologs of at least 1700 human disease genes. Over 1 million expressed sequence tags validated the annotation. More than one-third of the genome consists of transposable elements, with unusually prevalent DNA transposons. Like that of other tetrapods, the genome of X. tropicalis contains gene deserts enriched for conserved noncoding elements. The genome exhibits substantial shared synteny with human and chicken over major parts of large chromosomes, broken by lineage-specific chromosome fusions and fissions, mainly in the mammalian lineage.
C1 [Hellsten, Uffe; Shu, Shengqiang; Dubchak, Inna; Goodstein, David; Grigoriev, Igor V.; Grimwood, Jane; Lindquist, Erika; Lucas, Susan M.; Poliakov, Alexander V.; Salamov, Asaf; Schmutz, Jeremy; Terry, Astrid; Richardson, Paul M.; Rokhsar, Daniel S.] Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Harland, Richard M.; Hendrix, David; Dichmann, Darwin S.; Fletcher, Russell; Kawashima, Takeshi; Mitros, Therese; Wills, Andrea; Grammer, Timothy; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
[Gilchrist, Michael J.] MRC Natl Inst Med Res, Div Syst Biol, London NW7 1AA, England.
[Jurka, Jerzy; Kapitonov, Vladimir] Genet Informat Res Inst, Mountain View, CA 94043 USA.
[Ovcharenko, Ivan; Taher, Leila] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Putnam, Nicholas H.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA.
[Blitz, Ira L.; Blumberg, Bruce] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
[Amaya, Enrique] Univ Manchester, Healing Fdn Ctr, Manchester M13 9PT, Lancs, England.
[Detter, John C.] Los Alamos Natl Lab, DOE Joint Genome Inst, Los Alamos, NM 87545 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, Dhhs Bethesda, MD 20892 USA.
[Graves, Tina; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA.
[Grimwood, Jane; Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, Joint Genome Inst, Huntsville, AL 35806 USA.
[Kawashima, Takeshi] Okinawa Inst Sci & Technol, Okinawa 9042234, Japan.
[Mead, Paul E.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Ogino, Hajime] Nara Inst Sci & Technol, Nara, Japan.
[Ohta, Yuko] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Pollet, Nicolas] Univ Evry Val Essonne, CNRS, Programme Epigenom, F-91058 Evry, France.
[Robert, Jacques] Univ Rochester, Dept Microbiol & Immunol, Med Ctr, Rochester, NY 14642 USA.
[Sater, Amy K.; Wells, Dan] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
[Vize, Peter D.] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada.
[Zorn, Aaron M.] Cincinnati Childrens Hosp, Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
[Grainger, Robert] Dept Biol, Charlottesville, VA 22904 USA.
[Khokha, Mustafa K.] Yale Univ, Sch Med, Dept Pediat & Genet, New Haven, CT 06520 USA.
RP Hellsten, U (reprint author), Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
EM uhellsten@lbl.gov
RI Putnam, Nicholas/B-9968-2008; Dichmann, Darwin/C-7239-2012; Pollet,
Nicolas/A-4746-2013; Schmutz, Jeremy/N-3173-2013; Kawashima,
Takeshi/M-4510-2015
OI Putnam, Nicholas/0000-0002-1315-782X; Pollet,
Nicolas/0000-0002-9975-9644; Schmutz, Jeremy/0000-0001-8062-9172;
FU U.S. Department of Energy's Office of Science; University of California,
Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; Lawrence
Livermore National Laboratory [DE-AC52-07NA27344]; Los Alamos National
Laboratory [DE-AC02-06NA25396]; NIH, National Library of Medicine;
National Human Genome Research Institute (NHGRI) [U01 HG02155]; National
Institute of Child Health and Human Development
FX This work was performed under the auspices of the U.S. Department of
Energy's Office of Science, Biological and Environmental Research
Program, and by the University of California, Lawrence Berkeley National
Laboratory, under contract DE-AC02-05CH11231, Lawrence Livermore
National Laboratory under contract DE-AC52-07NA27344, and Los Alamos
National Laboratory under contract DE-AC02-06NA25396. This research was
supported in part by the Intramural Research Program of the NIH,
National Library of Medicine, and by a grant to R. K. W. from the
National Human Genome Research Institute (NHGRI U01 HG02155) with
supplemental funds provided by the National Institute of Child Health
and Human Development. We thank R. Gibbs and S. Scherer of the Human
Genome Sequencing Center, Baylor College of Medicine, for their
contributions to identification and mapping of simple sequence length
polymorphisms.
NR 23
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U1 13
U2 86
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD APR 30
PY 2010
VL 328
IS 5978
BP 633
EP 636
DI 10.1126/science.1183670
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589OJ
UT WOS:000277159800047
PM 20431018
ER
PT J
AU Demchenko, YN
Glebov, OK
Zingone, A
Keats, JJ
Bergsagel, PL
Kuehl, WM
AF Demchenko, Yulia N.
Glebov, Oleg K.
Zingone, Adriana
Keats, Jonathan J.
Bergsagel, P. Leif
Kuehl, W. Michael
TI Classical and/or alternative NF-kappa B pathway activation in multiple
myeloma
SO BLOOD
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; CELL-DEATH; KINASE; TNF; BINDING; TRAF3;
APOPTOSIS; SURVIVAL; COMPLEX; CIAP2
AB Mutations involving the nuclear factor-kappa B (NF-kappa B) pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCLs). These mutations, which are apparent progression events, enable MM tumors to become less dependent on bone marrow signals that activate NF-kappa B. Studies on a panel of 51 MMCLs provide some clarification of the mechanisms through which these mutations act and the significance of classical versus alternative activation of NF-kappa B. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, and TACI) selectively activate the classical pathway. However, most mutations affecting NF-kappa B-inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteasomal degradation of NIK in MM. Third, using transfection to selectively activate the classical or alternative NF-kappa B pathways, we show virtually identical changes in gene expression in one MMCL, whereas the changes are similar albeit nonidentical in a second MMCL. Our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NF-kappa B pathway. (Blood. 2010; 115(17): 3541-3552)
C1 [Kuehl, W. Michael] Bethesda Naval Hosp, Genet Branch, Ctr Canc Res, NCI,NIH, Bethesda, MD 20889 USA.
[Keats, Jonathan J.; Bergsagel, P. Leif] Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ USA.
RP Kuehl, WM (reprint author), Bethesda Naval Hosp, Genet Branch, Ctr Canc Res, NCI,NIH, Bldg 8,Rm 5101, Bethesda, MD 20889 USA.
EM wmk@helix.nih.gov
RI Bergsagel, Peter/A-7842-2011
OI Bergsagel, Peter/0000-0003-1523-7388
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research [CA100707, CA133966]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (grants CA100707 and CA133966; P. L. B.).
NR 45
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U1 1
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD APR 29
PY 2010
VL 115
IS 17
BP 3541
EP 3552
DI 10.1182/blood-2009-09-243535
PG 12
WC Hematology
SC Hematology
GA 591WL
UT WOS:000277335800019
PM 20053756
ER
PT J
AU Okamoto, K
Iwai, Y
Oh-hora, M
Yamamoto, M
Morio, T
Aoki, K
Ohya, K
Jetten, AM
Akira, S
Muta, T
Takayanagi, H
AF Okamoto, Kazuo
Iwai, Yoshiko
Oh-hora, Masatsugu
Yamamoto, Masahiro
Morio, Tomohiro
Aoki, Kazuhiro
Ohya, Keiichi
Jetten, Anton M.
Akira, Shizuo
Muta, Tatsushi
Takayanagi, Hiroshi
TI I kappa B zeta regulates T(H)17 development by cooperating with ROR
nuclear receptors
SO NATURE
LA English
DT Article
ID TH17 CELL-DIFFERENTIATION; ARYL-HYDROCARBON RECEPTOR; TARGETED
DISRUPTION; T-CELLS; GAMMA-T; IMMUNE-RESPONSES; BINDING-SITES;
TRANSCRIPTION; PROTEIN; INDUCTION
AB Interleukin (IL)-17-producing helper T (T(H)17) cells are a distinct T-cell subset characterized by its pathological role in autoimmune diseases(1-3). IL-6 and transforming growth factor-beta (TGF-beta) induce TH17 development, in which the orphan nuclear receptors, ROR gamma t and ROR alpha, have an indispensable role(4-6). However, in the absence of IL-6 and TGF-beta, the ectopic expression of ROR gamma t or ROR alpha leads to only a modest IL-17 production(5,7,8). Here we identify a nuclear I kappa B family member, I kappa B zeta (encoded by the Nfkbiz gene), as a transcription factor required for TH17 development in mice. The ectopic expression of I kappa B zeta in naive CD4(+) T cells together with ROR gamma t or ROR alpha potently induces T(H)17 development, even in the absence of IL-6 and TGF-beta. Notably, Nfkbiz(-/-) mice have a defect in T(H)17 development and a resistance to experimental autoimmune encephalomyelitis (EAE). The T-cell-intrinsic function of I kappa B zeta was clearly demonstrated by the resistance to EAE of the Rag2(-/-) mice into which Nfkbiz(-/-) CD4(+) T cells were transferred. In cooperation with ROR gamma t and RORa, I kappa B zeta enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. This study provides evidence for the transcriptional mechanisms underlying T(H)17 development and points to a molecular basis for a novel therapeutic strategy against autoimmune disease.
C1 [Okamoto, Kazuo; Oh-hora, Masatsugu; Takayanagi, Hiroshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Tokyo 1138549, Japan.
[Okamoto, Kazuo; Oh-hora, Masatsugu; Takayanagi, Hiroshi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence Program, Bunkyo Ku, Tokyo 1138549, Japan.
[Okamoto, Kazuo; Takayanagi, Hiroshi] Japan Sci & Technol Agcy, ERATO, Takayanagi Osteonetwork Project, Bunkyo Ku, Tokyo 1138549, Japan.
[Iwai, Yoshiko] Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Bunkyo Ku, Tokyo 1138510, Japan.
[Yamamoto, Masahiro] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Immune Regulat, Suita, Osaka 5650871, Japan.
[Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan.
[Morio, Tomohiro] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138519, Japan.
[Aoki, Kazuhiro; Ohya, Keiichi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Hard Tissue Engn Pharmacol, Bunkyo Ku, Tokyo 1138549, Japan.
[Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Muta, Tatsushi] Tohoku Univ, Grad Sch Life Sci, Lab Cell Recognit & Response, Aoba Ku, Sendai, Miyagi 9808578, Japan.
RP Takayanagi, H (reprint author), Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Yushima 1-5-45, Tokyo 1138549, Japan.
EM taka.csi@tmd.ac.jp
RI Akira, Shizuo/C-3134-2009
FU Japan Society for the Promotion of Science (JSPS); Ministry of
Education, Culture, Sports, Science and Technology of Japan (MEXT);
ERATO; JST; NIEHS [Z01-ES-101586]; Takeda Life Science Foundation;
Yokoyama Foundation; Ichiro Kanehara
FX We are grateful to Y. Iwakura and T. Kitamura for providing
Il17a-/- mice and retrovirus vectors, respectively. We also
thank M. Shinohara, T. Negishi-Koga, M. Asagiri, T. Nakashima, N.
Komatsu, M. Ohba, Y. Kunisawa, Y. Suzuki, S. Miyakoshi and T. Kunigami
for discussion and assistance. This work was supported in part by
Grant-in-Aid for Creative Scientific Research from the Japan Society for
the Promotion of Science (JSPS), Grant-in-Aid for Challenging
Exploratory Research from JSPS, Grant-in-Aid for JSPS Fellows,
Grants-in-Aid for GCOE Program from the Ministry of Education, Culture,
Sports, Science and Technology of Japan (MEXT), and ERATO, Takayanagi
Osteonetwork Project from JST. It was also supported by grants from the
Intramural Research Program of the NIEHS (Z01-ES-101586) (to A. M. J.),
Takeda Life Science Foundation and Yokoyama Foundation for Clinical
Pharmacology and the Ichiro Kanehara
NR 35
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U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1381
EP U13
DI 10.1038/nature08922
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000053
PM 20383124
ER
PT J
AU Taraska, JW
Zagotta, WN
AF Taraska, Justin W.
Zagotta, William N.
TI Fluorescence Applications in Molecular Neurobiology
SO NEURON
LA English
DT Review
ID RESONANCE ENERGY-TRANSFER; NUCLEOTIDE-GATED CHANNELS;
INTERNAL-REFLECTION FLUORESCENCE; PYRENE EXCIMER FLUORESCENCE;
PATCH-CLAMP FLUOROMETRY; VOLTAGE SENSOR MOVEMENT; REGULATORY
LIGHT-CHAIN; SHAKER K+ CHANNELS; SINGLE-MOLECULE; LIVING CELLS
AB Macromolecules drive the complex behavior of neurons. For example, channels and transporters control the movements of ions across membranes, SNAREs direct the fusion of vesicles at the synapse, and motors move cargo throughout the cell. Understanding the structure, assembly, and conformational movements of these and other neuronal proteins is essential to understanding the brain. Developments in fluorescence have allowed the architecture and dynamics of proteins to be studied in real time and in a cellular context with great accuracy. In this review, we cover classic and recent methods for studying protein structure, assembly, and dynamics with fluorescence. These methods include fluorescence and luminescence resonance energy transfer, single-molecule bleaching analysis, intensity measurements, colocalization microscopy, electron transfer, and bimolecular complementation analysis. We present the principles of these methods, highlight recent work that uses the methods, and discuss a framework for interpreting results as they apply to molecular neurobiology.
C1 [Taraska, Justin W.] NHLBI, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA.
[Zagotta, William N.] Univ Washington, Howard Hughes Med Inst, Dept Physiol & Biophys, Seattle, WA 98195 USA.
RP Taraska, JW (reprint author), NHLBI, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA.
EM taraskajw@mail.nih.gov; zagotta@u.washington.edu
RI Taraska, Justin/H-8876-2016
OI Taraska, Justin/0000-0001-5355-9535
FU Howard Hughes Medical Institute (HHMI); National Institutes of Health
(NIH); Jane Coffin Childs Foundation
FX We would like to thank Alex Merz, Anne Carlson, Michael Puljung, and
Noah Shuart for helpful comments on the manuscript. We would also like
to thank Wolfhard Almers, Ehud Isacoff, and David Farrens, who kindly
proved figures for reproduction. W.N.Z. was supported by the Howard
Hughes Medical Institute (HHMI) and National Institutes of Health (NIH).
J.W.T was supported by HHMI, the Jane Coffin Childs Foundation, and a
NIH Pathway to Independence Award.
NR 213
TC 33
Z9 33
U1 1
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD APR 29
PY 2010
VL 66
IS 2
BP 170
EP 189
DI 10.1016/j.neuron.2010.02.002
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA 591NQ
UT WOS:000277308200004
PM 20434995
ER
PT J
AU Fritsch, B
Reis, J
Martinowich, K
Schambra, HM
Ji, YY
Cohen, LG
Lu, B
AF Fritsch, Brita
Reis, Janine
Martinowich, Ken
Schambra, Heidi M.
Ji, Yuanyuan
Cohen, Leonardo G.
Lu, Bai
TI Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity:
Potential Implications for Motor Learning
SO NEURON
LA English
DT Article
ID LONG-TERM POTENTIATION; NONINVASIVE CORTICAL STIMULATION; VAL66MET
POLYMORPHISM; NEUROTROPHIC FACTOR; EXCITABILITY SHIFTS;
NEURONAL-ACTIVITY; CEREBRAL CORTEX; MEMORY; MODULATION; POLARIZATION
AB Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.
C1 [Reis, Janine; Schambra, Heidi M.; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Fritsch, Brita] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA.
[Fritsch, Brita; Reis, Janine] Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany.
[Ji, Yuanyuan; Lu, Bai] NICHHD, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA.
[Martinowich, Ken; Lu, Bai] NIMH, Gene Cognit & Psychosis Program GCAP, NIH, Bethesda, MD 20892 USA.
RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
EM cohenl@ninds.nih.gov; bai.b.lu@gsk.com
RI Lu, Bai/A-4018-2012; Martinowich, Keri/F-9841-2012;
OI Fritsch, Brita/0000-0003-4884-9049; Martinowich,
Keri/0000-0002-5237-0789
FU NINDS, NIH; Alexander von Humboldt Foundation Germany
FX This research was supported by the NINDS Intramural Research Program,
NIH (B.F., JR., H.M.S.), and the Alexander von Humboldt Foundation
Germany (JR.). We thank J.W. Krakauer and P.A. Celnik for helpful
comments and for their involvement in the previous characterization of
the motor task utilized. We thank F. Lee, A. Morozov, and D. Ginty
(transgenic animals), D. Ide and A. Mitz (field measurements), and D.
Brandsch and K. Spies (data analysis).
NR 41
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U1 10
U2 94
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD APR 29
PY 2010
VL 66
IS 2
BP 198
EP 204
DI 10.1016/j.neuron.2010.03.035
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 591NQ
UT WOS:000277308200006
PM 20434997
ER
PT J
AU Ginsberg, HN
Elam, MB
Lovato, LC
Crouse, JR
Leiter, LA
Linz, P
Friedewald, WT
Buse, JB
Gerstein, HC
Probstfield, J
Grimm, RH
Ismail-Beigi, F
Bigger, JT
Goff, DC
Cushman, WC
Simons-Morton, DG
Byington, RP
AF Ginsberg, Henry N.
Elam, Marshall B.
Lovato, Laura C.
Crouse, John R., III
Leiter, Lawrence A.
Linz, Peter
Friedewald, William T.
Buse, John B.
Gerstein, Hertzel C.
Probstfield, Jeffrey
Grimm, Richard H.
Ismail-Beigi, Faramarz
Bigger, J. Thomas
Goff, David C., Jr.
Cushman, William C.
Simons-Morton, Denise G.
Byington, Robert P.
CA ACCORD Study Grp
TI Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; TREATMENT PANEL-III;
CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; RISK-FACTORS;
MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; INTERVENTION TRIAL; LDL
CHOLESTEROL
AB BACKGROUND
We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.
METHODS
We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
RESULTS
The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = 0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P = 0.057 for interaction).
CONCLUSIONS
The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
C1 [Ginsberg, Henry N.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Elam, Marshall B.; Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Lovato, Laura C.; Goff, David C., Jr.; Byington, Robert P.] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Crouse, John R., III] Wake Forest Univ, Sch Med, Prevent Cardiol Program, Winston Salem, NC 27109 USA.
[Leiter, Lawrence A.] Univ Toronto, Toronto, ON, Canada.
[Linz, Peter] USN, Med Ctr, San Diego, CA 92152 USA.
[Friedewald, William T.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Friedewald, William T.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Buse, John B.] Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC USA.
[Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Probstfield, Jeffrey] Univ Washington, Seattle, WA 98195 USA.
[Grimm, Richard H.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
[Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA.
[Bigger, J. Thomas] Columbia Univ Coll Phys & Surg, Div Cardiol, New York, NY 10032 USA.
[Simons-Morton, Denise G.] NHLBI, Bethesda, MD 20892 USA.
RP Ginsberg, HN (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, Rm PH 10-305, New York, NY 10032 USA.
EM hng1@columbia.edu
RI Friedewald, William/C-8034-2011
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,
IAAY1-HC-9035, IAAY1-HC-1010]; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institute on Aging; National Eye
Institute; Centers for Disease Control and Prevention; General Clinical
Research Centers; Merck; Merck Schering-Plough; Bristol-Myers Squibb;
AstraZeneca; Abbott; Roche; Isis/Genzyme; GlaxoSmithKline; Novartis;
Pfizer; Regeneron/Sanofi-Aventis; National Lipid Association; Solvay;
Novo Nordisk; Amylin; Becton Dickinson; Eli Lilly; Hoffmann-La Roche;
GlycoMark; Wyeth; Daiichi Sankyo; Bayhill Therapeutics; LipoScience;
MannKind; Veritas; MicroIslet; Exsulin; GI Dynamics; Medtronic; Tolerex;
Osiris; Halozyme; InterKrin; Sanofi-Aventis; Dexcom; Johnson Johnson;
Fujisawa; Takeda; King; DaiichiSankyo; Gilead; Theravance; Pharmacopeia;
Sciele
FX Supported by the National Heart, Lung, and Blood Institute (contracts
N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182,
N01-HC-95183, N01-HC-95184, IAAY1-HC-9035, and IAAY1-HC-1010), the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Institute on Aging, the National Eye Institute, the Centers for
Disease Control and Prevention, and General Clinical Research Centers at
many sites. The following companies provided study medications,
equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical,
AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer Healthcare,
GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis
Pharmaceuticals, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and
Takeda Pharmaceuticals.; Dr. Ginsberg reports receiving consulting fees
from Merck, Merck Schering-Plough, Bristol-Myers Squibb, AstraZeneca,
Abbott, Roche, Isis/Genzyme, GlaxoSmithKline, Novartis, Pfizer, and
Regeneron/Sanofi-Aventis and grant support from Merck, Isis/Genzyme,
Roche, and AstraZeneca; Dr. Elam, receiving consulting fees from Pfizer,
Abbott, and Merck Schering-Plough; Dr. Crouse, receiving consulting fees
from the National Lipid Association, AstraZeneca, Merck, and Merck
Schering-Plough and grant support from AstraZeneca; Dr. Leiter,
receiving consulting fees from AstraZeneca, Merck, Pfizer, Roche, and
Solvay and grant support from AstraZeneca, Merck, Pfizer, and Roche; Dr.
Linz, having an equity interest in Pfizer, Novartis, and AstraZeneca;
Dr. Buse, receiving consulting fees from Novo Nordisk, Amylin, Becton
Dickinson, Eli Lilly, Hoffmann-La Roche, GlycoMark, Wyeth, Daiichi
Sankyo, Bristol-Myers Squibb, Bayhill Therapeutics, LipoScience,
MannKind, Veritas, MicroIslet, GlaxoSmithKline, Abbott, Exsulin, and GI
Dynamics and grant support from Amylin, Novo Nordisk, Medtronic, Eli
Lilly, Novartis, Tolerex, Osiris, Halozyme, Pfizer, Hoffmann-La Roche,
InterKrin, Merck, Sanofi-Aventis, Dexcom, Johnson & Johnson,
BristolMyers Squibb, and Fujisawa, having an equity interest in Insulet,
and providing expert testimony for Novo Nordisk; Dr. Gerstein, receiving
consulting fees from Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo
Nordisk, AstraZeneca, Bristol-Myers Squibb, Roche, Medtronic, Merck,
Bayer, Bioavail, and Janssen-Ortho, grant support from Sanofi-Aventis,
GlaxoSmithKline, Novo Nordisk, Merck, Pronova, and Roche, and lecture
fees from Sanofi-Aventis, GlaxoSmithKline, Solvay, Boehringer Ingelheim,
Servier, Bayer, Eli Lilly, Novo Nordisk, and Takeda; Dr. Probstfield,
receiving grant support from Sanofi-Aventis, Boehringer Ingelheim, and
Abbott; Dr. Grimm, receiving consulting and lecture fees and grant
support from Pfizer, Merck, and Novartis, consulting and lecture fees
from Takeda, and lecture fees from AstraZeneca, Forest Laboratories, and
Schering-Plough; Dr. Bigger, receiving consulting fees from Merck and
Roche; Dr. Goff, receiving consulting fees from Takeda and grant support
from Merck; and Dr. Cushman, receiving consulting fees from Novartis,
Takeda, Sanofi-Aventis, Bristol-Myers Squibb, King, DaiichiSankyo,
Gilead, Theravance, Pharmacopeia, and Sciele and grant support from
Novartis, GlaxoSmithKline, and Merck. No other potential conflict of
interest relevant to this article was reported.
NR 29
TC 1017
Z9 1045
U1 7
U2 61
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 29
PY 2010
VL 362
IS 17
BP 1563
EP 1574
DI 10.1056/NEJMoa1001282
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 589AX
UT WOS:000277117400005
ER
PT J
AU Cushman, WC
Evans, GW
Byington, RP
Goff, DC
Grimm, RH
Cutler, JA
Simons-Morton, DG
Basile, JN
Corson, MA
Probstfield, JL
Katz, L
Peterson, KA
Friedewald, WT
Buse, JB
Bigger, JT
Gerstein, HC
Ismail-Beigi, F
AF Cushman, William C.
Evans, Gregory W.
Byington, Robert P.
Goff, David C., Jr.
Grimm, Richard H., Jr.
Cutler, Jeffrey A.
Simons-Morton, Denise G.
Basile, Jan N.
Corson, Marshall A.
Probstfield, Jeffrey L.
Katz, Lois
Peterson, Kevin A.
Friedewald, William T.
Buse, John B.
Bigger, J. Thomas
Gerstein, Hertzel C.
Ismail-Beigi, Faramarz
TI Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MICROVASCULAR COMPLICATIONS; RISK; DISEASE; TRIAL; PREVENTION; HOT
AB BACKGROUND
There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., < 120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.
METHODS
A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
RESULTS
After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P = 0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P = 0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001).
CONCLUSIONS
In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)
C1 [Cushman, William C.] Memphis Vet Affairs VA Med Ctr, Prevent Med Sect, Memphis, TN USA.
[Evans, Gregory W.; Byington, Robert P.; Goff, David C., Jr.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Grimm, Richard H., Jr.] Univ Minnesota, Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
[Peterson, Kevin A.] Univ Minnesota, Dept Family Practice & Community Med, Minneapolis, MN USA.
[Cutler, Jeffrey A.; Simons-Morton, Denise G.] NHLBI, Bethesda, MD 20892 USA.
[Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Corson, Marshall A.; Probstfield, Jeffrey L.] Univ Washington, Dept Med, Seattle, WA USA.
[Buse, John B.] Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC USA.
[Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA.
RP Cushman, WC (reprint author), Vet Affairs Med Ctr, Cushman Prevent Med Sect 111Q, 1030 Jefferson Ave, Memphis, TN 38104 USA.
EM william.cushman@va.gov
RI Friedewald, William/C-8034-2011;
OI Peterson, Kevin/0000-0002-6914-8586
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
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute on Aging; National Eye Institute; Centers for Disease Control
and Prevention
FX Supported by contracts from the 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, and IAA#Y1-HC-9035 and
IAA#Y1-HC-1010). 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, contributed funding. The Centers for Disease Control and
Prevention funded substudies within ACCORD on cost-effectiveness and
health-related quality of life. General Clinical Research Centers
provide support at many sites. The following companies provided study
medications, equipment, or supplies: Abbott Laboratories, Amylin
Pharmaceutical, AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer
Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals,
Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare,
Sanofi-Aventis U.S., and Takeda.
NR 19
TC 1153
Z9 1190
U1 6
U2 58
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 29
PY 2010
VL 362
IS 17
BP 1575
EP 1585
DI 10.1056/NEJMoa1001286
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 589AX
UT WOS:000277117400006
ER
PT J
AU Barr, RG
Bluemke, DA
Kawut, SM
AF Barr, R. Graham
Bluemke, David A.
Kawut, Steven M.
CA MESA Lung Study Investigators
TI Emphysema, Airflow Obstruction, and Left Ventricular Filling REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Barr, R. Graham] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Kawut, Steven M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Barr, RG (reprint author), Columbia Univ, Med Ctr, Morningside Heights, New York, NY 10027 USA.
EM rgb9@columbia.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 29
PY 2010
VL 362
IS 17
BP 1640
EP 1641
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 589AX
UT WOS:000277117400022
ER
PT J
AU Przytycka, TM
Kim, YA
AF Przytycka, Teresa M.
Kim, Yoo-Ah
TI Network integration meets network dynamics
SO BMC BIOLOGY
LA English
DT Editorial Material
ID GENE-EXPRESSION; METABOLISM; MODELS
AB Molecular interaction networks provide a window on the workings of the cell. However, combining various types of networks into one coherent large-scale dynamic model remains a formidable challenge. A recent paper in BMC Systems Biology describes a promising step in this direction.
C1 [Przytycka, Teresa M.; Kim, Yoo-Ah] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20814 USA.
RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, NLM, 8000 Rockville Pike, Bethesda, MD 20814 USA.
EM przytyck@ncbi.nlm.nih.gov
FU Intramural NIH HHS
NR 10
TC 11
Z9 12
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD APR 28
PY 2010
VL 8
AR 48
DI 10.1186/1741-7007-8-48
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 601JB
UT WOS:000278053300001
PM 20513250
ER
PT J
AU Polonsky, TS
McClelland, RL
Jorgensen, NW
Bild, DE
Burke, GL
Guerci, AD
Greenland, P
AF Polonsky, Tamar S.
McClelland, Robyn L.
Jorgensen, Neal W.
Bild, Diane E.
Burke, Gregory L.
Guerci, Alan D.
Greenland, Philip
TI Coronary Artery Calcium Score and Risk Classification for Coronary Heart
Disease Prediction
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID INCIDENT CARDIOVASCULAR EVENTS; COMPUTED-TOMOGRAPHY; ATHEROSCLEROSIS;
CALCIFICATION; IMPROVE; WOMEN; MEN
AB Context The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear.
Objective To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk.
Design, Setting, and Participants CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1.
Main Outcome Measures Incident CHD events.
Results During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement=0.25; 95% confidence interval, 0.16-0.34; P<.001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2.
Conclusion In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories. JAMA. 2010; 303(16): 1610-1616
C1 [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[McClelland, Robyn L.; Jorgensen, Neal W.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Burke, Gregory L.] Wake Forest Univ, Div Publ Hlth Sci, Sch Med, Winston Salem, NC 27109 USA.
[Guerci, Alan D.] St Francis Hosp, Ctr Heart, Roslyn, NY USA.
RP Greenland, P (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 750 N Lake Shore Dr,11th Floor, Chicago, IL 60611 USA.
FU Pfizer; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159,
N01-HC-95169, 5T32HL069771]; National Center for Research Resources
[1UL1RR025741]
FX Financial Disclosures: Dr Guerci reports that he has received grant
suppot from Pfizer. Dr Greenland reports that he has served as a
consultant to Pfizer and GE/Toshiba. No other disclosures were
reported.; Funding/Support: MESA was supported by contracts N01-HC-95159
through N01-HC-95169 from the National Heart, Lung, and Blood Institute
(NHLBI). Dr Polonsky is supported by an NHLBI training grant in
cardiovascular epidemiology and prevention (grant 5T32HL069771). Dr
Greenland is supported by a grant from the National Center for Research
Resources (grant number 1UL1RR025741).
NR 24
TC 431
Z9 439
U1 4
U2 37
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 APR 28
PY 2010
VL 303
IS 16
BP 1610
EP 1616
DI 10.1001/jama.2010.461
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 588PQ
UT WOS:000277085200024
PM 20424251
ER
PT J
AU Luo, Q
Holroyd, T
Majestic, C
Cheng, X
Schechter, J
Blair, RJ
AF Luo, Qian
Holroyd, Tom
Majestic, Catherine
Cheng, Xi
Schechter, Julia
Blair, R. James
TI Emotional Automaticity Is a Matter of Timing
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GAMMA-BAND SYNCHRONIZATION; NEURAL MECHANISMS; LATERAL AMYGDALA;
VISUAL-ATTENTION; MAGNETOENCEPHALOGRAPHY; BRAIN; FEAR; RESPONSES;
SIGNALS; THREAT
AB There has been a long controversy concerning whether the amygdala's response to emotional stimuli is automatic or dependent on attentional load. Using magnoencephalography and an advanced beamformer source localization technique, we found that amygdala automaticity was a function of time: while early amygdala responding to emotional stimuli (40-140 ms) was unaffected by attentional load, later amygdala response (280-410 ms), subsequent to frontoparietal cortex activity, was modulated by attentional load.
C1 [Luo, Qian; Majestic, Catherine; Schechter, Julia; Blair, R. James] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Holroyd, Tom] NIMH, Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA.
[Cheng, Xi] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
RP Luo, Q (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K North Dr,Mail Stop Code 2670, Bethesda, MD 20892 USA.
EM luoj@mail.nih.gov
FU National Institute of Mental Health
FX This research was supported by the National Institute of Mental Health
Intramural Research Program.
NR 41
TC 52
Z9 61
U1 5
U2 21
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 APR 28
PY 2010
VL 30
IS 17
BP 5825
EP 5829
DI 10.1523/JNEUROSCI.BC-5668-09.2010
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 589OF
UT WOS:000277159200002
PM 20427643
ER
PT J
AU Lemaitre, H
Mattay, VS
Sambataro, F
Verchinski, B
Straub, RE
Callicott, JH
Kittappa, R
Hyde, TM
Lipska, BK
Kleinman, JE
McKay, R
Weinberger, DR
AF Lemaitre, Herve
Mattay, Venkata S.
Sambataro, Fabio
Verchinski, Beth
Straub, Richard E.
Callicott, Joseph H.
Kittappa, Raja
Hyde, Thomas M.
Lipska, Barbara K.
Kleinman, Joel E.
McKay, Ronald
Weinberger, Daniel R.
TI Genetic Variation in FGF20 Modulates Hippocampal Biology
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; PARKINSONS-DISEASE; FACTOR RECEPTOR-1;
ALPHA-SYNUCLEIN; HUMAN BRAIN; EXPRESSION; RISK; SCHIZOPHRENIA;
ASSOCIATION; SIBLINGS
AB We explored the effect of single-nucleotide polymorphisms (SNPs) in the fibroblast growth factor 20 gene (FGF20) associated with risk for Parkinson's disease on brain structure and function in a large sample of healthy young-adult human subjects and also in elderly subjects to look at the interaction between genetic variations and age (N = 237; 116 men; 18-87 years). We analyzed high-resolution anatomical magnetic resonance images using voxel-based morphometry, a quantitative neuroanatomical technique. We also measured FGF20 mRNA expression in postmortem human brain tissue to determine the molecular correlates of these SNPs (N = 108; 72 men; 18-74 years). We found that the T allele carriers of rs12720208 in the 3'-untranslated region had relatively larger hippocampal volume (p = 0.0059) and diminished verbal episodic memory (p = 0.048) and showed steeper decreases of hippocampal volume with normal aging (p = 0.026). In postmortem brain, T allele carriers had greater expression of hippocampal FGF20 mRNA (p = 0.037), consistent with a previously characterized microRNA mechanism. The C allele matches a predicted miR-433 microRNA binding domain, whereas the T allele disrupts it, resulting in higher FGF20 protein translation. The strong FGF20 genetic effects in hippocampus are presumably mediated by activation of the FGFR1 (FGF receptor 1), which is expressed in mammalian brain most abundantly in the hippocampus. These associations, from mRNA expression to brain morphology to cognition and an interaction with aging, confirm a role of FGF20 in human brain structure and function during development and aging.
C1 [Weinberger, Daniel R.] NIMH, Clin Brain Disorder Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA.
[Kittappa, Raja; McKay, Ronald] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorder Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010;
OI Sambataro, Fabio/0000-0003-2102-416X; Lemaitre,
Herve/0000-0002-5952-076X; Callicott, Joseph/0000-0003-1298-3334
FU National Institute of Mental Health-National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health-National Institutes of Health.
NR 29
TC 11
Z9 11
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 APR 28
PY 2010
VL 30
IS 17
BP 5992
EP 5997
DI 10.1523/JNEUROSCI.5773-09.2010
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 589OF
UT WOS:000277159200017
PM 20427658
ER
PT J
AU Cea-del Rio, CA
Lawrence, JJ
Tricoire, L
Erdelyi, F
Szabo, G
McBain, CJ
AF Cea-del Rio, Christian A.
Lawrence, J. Josh
Tricoire, Ludovic
Erdelyi, Ferenc
Szabo, Gabor
McBain, Chris J.
TI M3 Muscarinic Acetylcholine Receptor Expression Confers Differential
Cholinergic Modulation to Neurochemically Distinct Hippocampal Basket
Cell Subtypes
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID RAT HIPPOCAMPUS; NETWORK OSCILLATIONS; METABOTROPIC GLUTAMATE;
POSTSYNAPTIC POTENTIALS; PERISOMATIC INHIBITION; ALZHEIMERS-DISEASE;
THETA-OSCILLATIONS; GAMMA-OSCILLATIONS; WORKING-MEMORY; GABA RELEASE
AB Cholinergic neuromodulation of hippocampal circuitry promotes network oscillations and facilitates learning and memory through cellular actions on both excitatory and inhibitory circuits. Despite widespread recognition that neurochemical content discriminates between functionally distinct interneuron populations, there has been no systematic examination of whether neurochemically distinct interneuron classes undergo differential cholinergic neuromodulation in the hippocampus. Using GFP transgenic mice that enable the visualization of perisomatically targeting parvalbumin-positive (PV+) or cholecystokinin-positive (CCK+) basket cells (BCs), we tested the hypothesis that neurochemically distinct interneuron populations are differentially engaged by muscarinic acetylcholine receptor (mAChR) activation. Cholinergic fiber activation revealed that CCK BCs were more sensitive to synaptic release of ACh than PV BCs. In response to depolarizing current steps, mAChR activation of PV BCs and CCK BCs also elicited distinct cholinergic response profiles, differing in mAChR-induced changes in action potential (AP) waveform, firing frequency, and intrinsic excitability. In contrast to PV BCs, CCK BCs exhibited a mAChR-induced after depolarization (mADP) that was frequency and activity-dependent. Pharmacological, molecular, and loss-of-function data converged on the presence of M3 mAChRs in distinguishing CCK BCs from PV BCs. Firing frequency of CCK BCs was controlled through M3 mAChRs but PV BC excitability was altered solely through M1 mAChRs. Finally, upon mAChR activation, glutamatergic transmission enhanced cellular excitability preferentially in CCK BCs but not in PV BCs. Our findings demonstrate that cell type-specific cholinergic specializations are present on neurochemically distinct interneuron subtypes in the hippocampus, revealing an organizing principle that cholinergic neuromodulation depends critically on neurochemical identity.
C1 [Lawrence, J. Josh] Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
[Cea-del Rio, Christian A.; Lawrence, J. Josh; Tricoire, Ludovic; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, Bethesda, MD 20892 USA.
[Erdelyi, Ferenc; Szabo, Gabor] Hungarian Acad Sci, Inst Expt Med, Lab Mol Biol & Genet, H-1450 Budapest, Hungary.
RP Lawrence, JJ (reprint author), Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Struct & Funct Neurosci, 391 Skaggs Bldg, Missoula, MT 59812 USA.
EM josh.lawrence@umontana.edu
RI Szabo, Gabor/A-5087-2008
OI Szabo, Gabor/0000-0001-5438-5151
FU National Institute of Child Health and Human Development (NICHD);
National Institutes of Health, National Center for Research Resources
[P20RR015583]
FX National Institute of Child Health and Human Development (NICHD)
intramural funding (C.Mc.B.) and National Institutes of Health Grant
P20RR015583 from the Centers of Biomedical Research Excellence Program
of the National Center for Research Resources (J.L.) supported this
work. We are grateful to Drs. Bruno Cauli for primers, Z. Josh Huang for
line B13 PV-GFP mice, Jurgen Wess for all muscarinic acetylcholine
receptor knock-out mice, and Vincent Schram and the NICHD Microscopy and
Imaging Core for assisting in the acquisition of tiled three-dimensional
confocal images of biocytin-labeled cells. We also thank Brian Jeffries
for immunocytochemistry and biocytin labeling, David Bonislawski for
confocal imaging and immunocytochemistry, and members of the McBain and
Lawrence laboratories for helpful comments on the manuscript.
NR 62
TC 39
Z9 39
U1 1
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 APR 28
PY 2010
VL 30
IS 17
BP 6011
EP 6024
DI 10.1523/JNEUROSCI.5040-09.2010
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 589OF
UT WOS:000277159200019
PM 20427660
ER
PT J
AU Petralia, RS
Wang, YX
Hua, F
Yi, Z
Zhou, A
Ge, L
Stephenson, FA
Wenthold, RJ
AF Petralia, R. S.
Wang, Y. X.
Hua, F.
Yi, Z.
Zhou, A.
Ge, L.
Stephenson, F. A.
Wenthold, R. J.
TI ORGANIZATION OF NMDA RECEPTORS AT EXTRASYNAPTIC LOCATIONS
SO NEUROSCIENCE
LA English
DT Article
DE PSD-95; SAP102; cadherin; catenin; NR2A; NR2B
ID CULTURED HIPPOCAMPAL-NEURONS; VESICULAR GLUTAMATE RELEASE; SOMATIC
SENSORY CORTEX; AMPA RECEPTORS; N-CADHERIN; POSTNATAL-DEVELOPMENT;
SYNAPSE FORMATION; DENDRITIC SPINES; BETA-CATENIN; RAT RETINA
AB NMDA receptors are found in neurons both at synapses and in extrasynaptic locations. Extrasynaptic locations are poorly characterized. Here we used preembedding immunoperoxidase and postembedding immunogold electron microscopy and fluorescence light microscopy to characterize extrasynaptic NMDA receptor locations in dissociated hippocampal neurons in vitro and in the adult and postnatal hippocampus in vivo. We found that extrasynaptic NMDA receptors on neurons in vivo and in vitro were usually concentrated at points of contact with adjacent processes, which were mainly axons, axon terminals, or glia. Many of these contacts were shown to contain adhesion factors such as cadherin and catenin. We also found associations of extrasynaptic NMDA receptors with the membrane associated guanylate kinase (MAGUKs), postsynaptic density (PSD)-95 and SAP102. Developmental differences were also observed. At postnatal day 2 in vivo, extrasynaptic NMDA receptors could often be found at sites with distinct densities whereas dense material was seen only rarely at sites of extrasynaptic NMDA receptors in the adult hippocampus in vivo. This difference probably indicates that many sites of extrasynaptic NMDA receptors in early postnatal ages represent synapse formation or possibly sites for synapse elimination. At all ages, as suggested in both in vivo and in vitro studies, extrasynaptic NMDA receptors on dendrites or the sides of spines may form complexes with other proteins, in many cases, at stable associations with adjacent cell processes. These associations may facilitate unique functions for extrasynaptic NMDA receptors. Published by Elsevier Ltd on behalf of IBRO.
C1 [Petralia, R. S.; Wang, Y. X.; Hua, F.; Yi, Z.; Zhou, A.; Ge, L.; Wenthold, R. J.] NIDCD, Neurochem Lab, NIH, Bethesda, MD USA.
[Stephenson, F. A.] Univ London, Sch Pharm, London WC1N 1AX, England.
RP Petralia, RS (reprint author), NIDCD, Neurochem Lab, NIH, Bethesda, MD USA.
EM petralia@nidcd.nih.gov
FU NIDCD; ORWH-FAES NIH
FX We thank Nicole Thompson for help formatting the references, and Dr.
Inna A. Belyantseva for helpful comments on the text. Research was
supported by the NIDCD Intramural Research Program. A.Z. was funded (in
part) by ORWH-FAES NIH.
NR 99
TC 92
Z9 96
U1 1
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD APR 28
PY 2010
VL 167
IS 1
BP 68
EP 87
DI 10.1016/j.neuroscience.2010.01.022
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA 578YS
UT WOS:000276333700008
PM 20096331
ER
PT J
AU Gordon, A
Videa, E
Saborio, S
Lopez, R
Kuan, G
Balmaseda, A
Harris, E
AF Gordon, Aubree
Videa, Elsa
Saborio, Saira
Lopez, Roger
Kuan, Guillermina
Balmaseda, Angel
Harris, Eva
TI Diagnostic Accuracy of a Rapid Influenza Test for Pandemic Influenza A
H1N1
SO PLOS ONE
LA English
DT Article
ID YOUNG-CHILDREN; IMPACT; PERFORMANCE; MANAGEMENT
AB Background: With the current influenza A H1N1 pandemic (H1N1pdm), it is extremely important that clinicians can quickly and accurately identify influenza cases.
Methodology/Principal Findings: To investigate the performance of the QuickVue Influenza A+B rapid test, we conducted a prospective study of the diagnostic accuracy of the QuickVue Influenza A+B test compared to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for influenza A H1N1pdm in Nicaraguan children aged 2 to 14 years. Rapid test sensitivity and specificity compared to real-time RT-PCR were 64.1% (95% CI 53.5, 73.9) and 98.3% (95.0, 99.6), respectively. Agreement between the two tests was 86.4% (95% CI 81.7, 90.3), and kappa was calculated to be 0.67 (95% CI 0.56, 0.76). Performance of the rapid test varied by day of presentation, with a sensitivity of 41.7% (95% CI 22.1, 63.4) for samples from children presenting on the day of symptom onset and a sensitivity of 72.1% (95% CI 59.9, 82.3) for samples from children presenting one or more days post-symptom onset.
Conclusions/Significance: We found that the rapid test performed with moderate sensitivity and high specificity. Test performance varied by day of onset, with lower sensitivity on the day of symptom onset.
C1 [Gordon, Aubree] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
[Gordon, Aubree] NIH, John E Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Videa, Elsa] Sustainable Sci Inst, Managua, Nicaragua.
[Saborio, Saira; Lopez, Roger; Balmaseda, Angel] Minist Hlth, Dept Virol, Ctr Nacl Diagnost & Referencia, Managua, Nicaragua.
[Kuan, Guillermina] Minist Hlth, Ctr Salud Socrates Flores Vivas, Managua, Nicaragua.
[Harris, Eva] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA.
RP Gordon, A (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
EM aubree@berkeley.edu
OI Gordon, Aubree/0000-0002-9352-7877
FU John E. Fogarty International Center; National Institutes of Allergy and
Infectious Disease; Pediatric Dengue Vaccine Initiative [VE-1]
FX This study was funded by the John E. Fogarty International Center, the
National Institutes of Allergy and Infectious Disease, and the Pediatric
Dengue Vaccine Initiative (VE-1). Rapid tests were provided free of
charge by Quidel Corporation. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 16
TC 22
Z9 23
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 28
PY 2010
VL 5
IS 4
AR e10364
DI 10.1371/journal.pone.0010364
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589MV
UT WOS:000277154200006
PM 20442773
ER
PT J
AU Hong, SK
Levin, CS
Brown, JL
Wan, HY
Sherman, BT
Huang, DW
Lempicki, RA
Feldman, B
AF Hong, Sung-Kook
Levin, Carly S.
Brown, Jamie L.
Wan, Haiyan
Sherman, Brad T.
Huang, Da Wei
Lempicki, Richard A.
Feldman, Benjamin
TI Pre-gastrula expression of zebrafish extraembryonic genes
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID YOLK SYNCYTIAL LAYER; EMBRYONIC-DEVELOPMENT; ENDODERM FORMATION;
DANIO-RERIO; MOLECULAR-CLONING; ENVELOPING LAYER; CELL; SIGNALS;
VERTEBRATE; FAMILY
AB Background: Many species form extraembryonic tissues during embryogenesis, such as the placenta of humans and other viviparous mammals. Extraembryonic tissues have various roles in protecting, nourishing and patterning embryos. Prior to gastrulation in zebrafish, the yolk syncytial layer - an extraembryonic nuclear syncytium - produces signals that induce mesoderm and endoderm formation. Mesoderm and endoderm precursor cells are situated in the embryonic margin, an external ring of cells along the embryo-yolk interface. The yolk syncytial layer initially forms below the margin, in a domain called the external yolk syncytial layer (E-YSL).
Results: We hypothesize that key components of the yolk syncytial layer's mesoderm and endoderm inducing activity are expressed as mRNAs in the E-YSL. To identify genes expressed in the E-YSL, we used microarrays to compare the transcription profiles of intact pre-gastrula embryos with pre-gastrula embryonic cells that we had separated from the yolk and yolk syncytial layer. This identified a cohort of genes with enriched expression in intact embryos. Here we describe our whole mount in situ hybridization analysis of sixty-eight of them. This includes ten genes with E-YSL expression (camsap1l1, gata3, znf503, hnf1ba, slc26a1, slc40a1, gata6, gpr137bb, otop1 and cebpa), four genes with expression in the enveloping layer (EVL), a superficial epithelium that protects the embryo (zgc:136817, zgc:152778, slc14a2 and elovl6l), three EVL genes whose expression is transiently confined to the animal pole (elovl6l, zgc:136359 and clica), and six genes with transient maternal expression (mtf1, wu:fj59f04, mospd2, rftn2, arrdc1a and pho). We also assessed the requirement of Nodal signaling for the expression of selected genes in the E-YSL, EVL and margin. Margin expression was Nodal dependent for all genes we tested, including the concentrated margin expression of an EVL gene: zgc:110712. All other instances of EVL and E-YSL expression that we tested were Nodal independent.
Conclusion: We have devised an effective strategy for enriching and identifying genes expressed in the E-YSL of pre-gastrula embryos. To our surprise, maternal genes and genes expressed in the EVL were also enriched by this strategy. A number of these genes are promising candidates for future functional studies on early embryonic patterning.
C1 [Hong, Sung-Kook; Levin, Carly S.; Brown, Jamie L.; Wan, Haiyan; Feldman, Benjamin] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Sherman, Brad T.; Huang, Da Wei; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Feldman, B (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RI Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Feldman,
Benjamin/0000-0003-4838-8641
FU National Human Genome Research Institute; National Cancer Institutes,
National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and National Cancer Institutes,
National Institutes of Health. We thank Erich Roessler for his critical
reading of the manuscript and Darryl Leja for the expert graphic
illustrations.
NR 61
TC 12
Z9 12
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD APR 27
PY 2010
VL 10
AR 42
DI 10.1186/1471-213X-10-42
PG 11
WC Developmental Biology
SC Developmental Biology
GA 598PH
UT WOS:000277849700001
PM 20423468
ER
PT J
AU Kenet, G
Lutkhoff, LK
Albisetti, M
Bernard, T
Bonduel, M
Brandao, L
Chabrier, S
Chan, A
deVeber, G
Fiedler, B
Fullerton, HJ
Goldenberg, NA
Grabowski, E
Gunther, G
Heller, C
Holzhauer, S
Iorio, A
Journeycake, J
Junker, R
Kirkham, FJ
Kurnik, K
Lynch, JK
Male, C
Manco-Johnson, M
Mesters, R
Monagle, P
van Ommen, CH
Raffini, L
Rostasy, K
Simioni, P
Strater, RD
Young, G
Nowak-Gottl, U
AF Kenet, Gili
Luetkhoff, Lisa K.
Albisetti, Manuela
Bernard, Timothy
Bonduel, Mariana
Brandao, Leonardo
Chabrier, Stephane
Chan, Anthony
deVeber, Gabrielle
Fiedler, Barbara
Fullerton, Heather J.
Goldenberg, Neil A.
Grabowski, Eric
Guenther, Gudrun
Heller, Christine
Holzhauer, Susanne
Iorio, Alfonso
Journeycake, Janna
Junker, Ralf
Kirkham, Fenella J.
Kurnik, Karin
Lynch, John K.
Male, Christoph
Manco-Johnson, Marilyn
Mesters, Rolf
Monagle, Paul
van Ommen, C. Heleen
Raffini, Leslie
Rostasy, Kevin
Simioni, Paolo
Straeter, Ronald D.
Young, Guy
Nowak-Goettl, Ulrike
TI Impact of Thrombophilia on Risk of Arterial Ischemic Stroke or Cerebral
Sinovenous Thrombosis in Neonates and Children A Systematic Review and
Meta-Analysis of Observational Studies
SO CIRCULATION
LA English
DT Article
DE cerebrovascular disorders; meta-analysis; pediatrics; thrombophilia
ID FACTOR-V-LEIDEN; VENOUS SINUS THROMBOSIS; GENE G20210A MUTATION;
PROTHROMBIN 20210 G; CHILDHOOD STROKE; PROTEIN-C; PEDIATRIC STROKE;
METHYLENETETRAHYDROFOLATE REDUCTASE; ANTIPHOSPHOLIPID ANTIBODIES;
HOMOCYSTEINE METABOLISM
AB Background-The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies.
Methods and Results-A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99).
Conclusions-The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated. (Circulation. 2010; 121: 1838-1847)
C1 [Luetkhoff, Lisa K.; Straeter, Ronald D.; Nowak-Goettl, Ulrike] Univ Hosp Munster, Dept Pediat Hematol Oncol, D-48149 Munster, Germany.
[Kenet, Gili] Chaim Sheba Med Ctr, Israel Natl Haemophilia Ctr, IL-52621 Tel Hashomer, Israel.
[Albisetti, Manuela] Univ Childrens Hosp, Div Hematol, Zurich, Switzerland.
[Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Univ Colorado, Dept Pediat Hematol Oncol BMT, Denver, CO 80202 USA.
[Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Univ Colorado, Mt States Reg Hemophilia & Thrombosis Ctr, Denver, CO 80202 USA.
[Bernard, Timothy; Goldenberg, Neil A.; Manco-Johnson, Marilyn] Childrens Hosp, Denver, CO 80218 USA.
[Bonduel, Mariana] Hosp Pediat Prof Dr JP Garrahan, Serv Hematolgia & Oncol, Buenos Aires, DF, Argentina.
[Brandao, Leonardo; deVeber, Gabrielle] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Chabrier, Stephane] CHU, Unit Neonatol & Reanimat Pediat, St Etienne, France.
[Chan, Anthony] McMaster Univ, Hamilton, ON, Canada.
[Fiedler, Barbara] Univ Hosp Munster, Dept Pediat Neurol, D-48149 Munster, Germany.
[Fullerton, Heather J.] Univ Calif San Francisco, Dept Neurol & Pediat, San Francisco, CA 94143 USA.
[Grabowski, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Guenther, Gudrun] Univ Hosp Magdeburg, Dept Pediat, Magdeburg, Germany.
[Heller, Christine] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany.
[Holzhauer, Susanne] Charite, Dept Pediat Hematol Oncol, Berlin, Germany.
[Iorio, Alfonso] Univ Perugia, Internal & Vasc Med & Hemophilia Ctr, I-06100 Perugia, Italy.
[Journeycake, Janna] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Med Ctr Dallas, Dallas, TX 75390 USA.
[Junker, Ralf] Univ Hosp Kiel, Dept Clin Chem, Kiel, Germany.
[Kirkham, Fenella J.] UCL, Neurosci Unit, Inst Child Hlth, London, England.
[Kirkham, Fenella J.] Southampton Gen Hosp, Dept Child Hlth, Southampton SO9 4XY, Hants, England.
[Kurnik, Karin] Univ Hosp Munich, Dept Pediat, Munich, Germany.
[Lynch, John K.] Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut, Bethesda, MD USA.
[Male, Christoph] Med Univ Vienna, Dept Pediat, Vienna, Austria.
[Mesters, Rolf] Univ Hosp Munster, Dept Internal Med, D-48149 Munster, Germany.
[Monagle, Paul] Royal Childrens Hosp, Parkville, Vic, Australia.
[van Ommen, C. Heleen] Emma Childrens Hosp AMC, Dept Pediat Hematol, Amsterdam, Netherlands.
[Raffini, Leslie] Univ Penn, Sch Med, Div Hematol, Dept Pediat,Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Rostasy, Kevin] Med Univ Innsbruck, Dept Pediat 4, Div Pediat Neurol & Inherited Metab Disorders, Innsbruck, Austria.
[Simioni, Paolo] Univ Padua, Dept Cardiol Thorac & Vasc Sci, Chair Internal Med 2, Padua, Italy.
[Young, Guy] Childrens Hosp, Div Hematol Oncol, Los Angeles, CA 90027 USA.
RP Nowak-Gottl, U (reprint author), Univ Hosp Munster, Dept Pediat Hematol Oncol, Albert Schweitzer Str 33, D-48149 Munster, Germany.
EM leagottl@uni-muenster.de
RI Kirkham, Fenella/C-2442-2009; Young, Guy/I-1880-2012; Junker,
Ralf/M-2358-2013;
OI Iorio, Alfonso/0000-0002-3331-8766; Kirkham,
Fenella/0000-0002-2443-7958; Young, Guy/0000-0001-6013-1254; SIMIONI,
PAOLO/0000-0002-6744-383X; Chan, Anthony K. C./0000-0003-1551-3995
FU Forderverein "Schlaganfall und Thrombosen im Kindesalter e.V.,";
Deutsche Schlaganfall-Hilfe; Interdisziplinares Zentrum fur Klinische
Forschung [CRA01-09]; University of Munster
FX The study was supported by grants from the Forderverein "Schlaganfall
und Thrombosen im Kindesalter e.V.," Deutsche Schlaganfall-Hilfe, and
Interdisziplinares Zentrum fur Klinische Forschung (CRA01-09),
University of Munster. These study supporters had no role in study
design, data collection, data analysis, data interpretation, or writing
of the report.
NR 93
TC 156
Z9 173
U1 2
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 27
PY 2010
VL 121
IS 16
BP 1838
EP U92
DI 10.1161/CIRCULATIONAHA.109.913673
PG 25
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 588HD
UT WOS:000277058500007
PM 20385928
ER
PT J
AU Fleg, JL
AF Fleg, Jerome L.
TI Breathing Not Properly During Exercise Prognostic Implications in Heart
Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE cardiopulmonary exercise testing; heart failure; oscillatory breathing;
mortality; morbidity
ID CHEYNE-STOKES RESPIRATION; CARDIAC TRANSPLANTATION; VENTILATORY
EFFICIENCY; OXYGEN-CONSUMPTION; MORTALITY; CARDIOMYOPATHY; IMPAIRMENT;
SECONDARY
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
NR 18
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 27
PY 2010
VL 55
IS 17
BP 1824
EP 1825
DI 10.1016/j.jacc.2009.12.039
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 585UI
UT WOS:000276854500008
PM 20413032
ER
PT J
AU Gauthier, J
Champagne, N
Lafreniere, RG
Xiong, L
Spiegelman, D
Brustein, E
Lapointe, M
Peng, HS
Cote, M
Noreau, A
Hamdan, FF
Addington, AM
Rapoport, JL
DeLisi, LE
Krebs, MO
Joober, R
Fathalli, F
Mouaffak, F
Haghighi, AP
Neri, C
Dube, MP
Samuels, ME
Marineau, C
Stone, EA
Awadalla, P
Barker, PA
Carbonetto, S
Drapeau, P
Rouleau, GA
AF Gauthier, Julie
Champagne, Nathalie
Lafreniere, Ronald G.
Xiong, Lan
Spiegelman, Dan
Brustein, Edna
Lapointe, Mathieu
Peng, Huashan
Cote, Melanie
Noreau, Anne
Hamdan, Fadi F.
Addington, Anjene M.
Rapoport, Judith L.
DeLisi, Lynn E.
Krebs, Marie-Odile
Joober, Ridha
Fathalli, Ferid
Mouaffak, Faycal
Haghighi, Ali P.
Neri, Christian
Dube, Marie-Pierre
Samuels, Mark E.
Marineau, Claude
Stone, Eric A.
Awadalla, Philip
Barker, Philip A.
Carbonetto, Salvatore
Drapeau, Pierre
Rouleau, Guy A.
CA S2D Team
TI De novo mutations in the gene encoding the synaptic scaffolding protein
SHANK3 in patients ascertained for schizophrenia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CHROMOSOME 22Q; BIPOLAR DISORDER; PREMORBID IQ; LINKAGE; EXPRESSION;
GENOME; TRANSMISSION; ZEBRAFISH; ALLELES; LOCUS
AB Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.
C1 [Gauthier, Julie; Lafreniere, Ronald G.; Xiong, Lan; Spiegelman, Dan; Cote, Melanie; Noreau, Anne; Marineau, Claude; Rouleau, Guy A.] Univ Montreal, CHU Montreal, Res Ctr, Ctr Excellence Neurom, Montreal, PQ H2L 2W5, Canada.
[Gauthier, Julie; Lafreniere, Ronald G.; Xiong, Lan; Spiegelman, Dan; Cote, Melanie; Noreau, Anne; Marineau, Claude; Rouleau, Guy A.] Univ Montreal, Dept Med, Montreal, PQ H2L 2W5, Canada.
[Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Peng, Huashan; Drapeau, Pierre] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada.
[Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Peng, Huashan; Drapeau, Pierre] Univ Montreal, Grp Rech Syst Nerveux Cent, Montreal, PQ H3T 1J4, Canada.
[Hamdan, Fadi F.; Samuels, Mark E.; S2D Team] Univ Montreal, Ctr Excellence Neurom, CHU St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada.
[Addington, Anjene M.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[DeLisi, Lynn E.] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Brockton, MA 02301 USA.
[Krebs, Marie-Odile; Mouaffak, Faycal] Univ Paris 05, Lab Pathophysiol Psychiat Dis, U894, Hop St Anne, F-75014 Paris, France.
[Joober, Ridha; Fathalli, Ferid] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada.
[Haghighi, Ali P.; Carbonetto, Salvatore] McGill Univ, Dept Physiol, Montreal, PQ H3G 0B1, Canada.
[Neri, Christian] Ctr Paul Broca, INSERM, U857, F-75014 Paris, France.
[Dube, Marie-Pierre] Univ Montreal, Ctr Rech, Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada.
[Dube, Marie-Pierre] Univ Montreal, Dept Pharmacol, Montreal, PQ H1T 1C8, Canada.
[Stone, Eric A.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Awadalla, Philip] Univ Montreal, Res Ctr, CHU St Justine, Montreal, PQ H3T 1C5, Canada.
[Awadalla, Philip] Univ Montreal, Dept Pediat & Biochem, Montreal, PQ H3T 1C5, Canada.
[Barker, Philip A.] McGill Univ, Montreal Neurol Inst, Ctr Neuronal Survival, Montreal, PQ H3A 2B4, Canada.
[Carbonetto, Salvatore] McGill Univ, Ctr Res Neurosci, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada.
RP Gauthier, J (reprint author), Univ Montreal, CHU Montreal, Res Ctr, Ctr Excellence Neurom, Montreal, PQ H2L 2W5, Canada.
EM julie.gauthier@crchum.qc.ca; guy.rouleau@umontreal.ca
RI Neri, Christian/F-6729-2013; Dube, Marie-Pierre/B-9364-2008; Stone,
Eric/Q-7840-2016
OI Dube, Marie-Pierre/0000-0001-8442-4393;
FU Genome Canada and Genome Quebec; Universite de Montreal for the Synapse
to Disease; Canadian Foundation for Innovation
FX We thank all the families involved in this study. We would like to thank
Dr. Chawki Benkelfat for several helpful discussions. We also
acknowledge the efforts of the members of the Genome Quebec Innovation
Centre Sequencing (Pierre Lepage, Sebastien Brunet, and Hao Fan Yam) and
Bioinformatic (Louis Letourneau and Louis Dumond Joseph) groups. This
work was supported by Genome Canada and Genome Quebec, and received
cofunding from Universite de Montreal for the Synapse to Disease (S2D)
project as well as funding from the Canadian Foundation for Innovation.
G. A. R. holds the Canada Research Chair in Genetics of the Nervous
System; P. D. holds the Canada Research Chair in Neuroscience. A. P. H.
holds the Canada Research Chair in Drosophila Neurobiology. P. A. holds
a career award from the Fonds de la recherche en Sante du Quebec. A
portion of the schizophrenia cohort was collected through the
Collaborative Network for Family Study in Psychiatry (Reseau d'etude
Familiale en Psychiatry), supported by the Fondation Pierre Deniker.
NR 42
TC 172
Z9 178
U1 6
U2 20
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 27
PY 2010
VL 107
IS 17
BP 7863
EP 7868
DI 10.1073/pnas.0906232107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 588QQ
UT WOS:000277088700048
PM 20385823
ER
PT J
AU Meng, XL
Shen, JS
Kawagoe, S
Ohashi, T
Brady, RO
Eto, Y
AF Meng, Xing-Li
Shen, Jin-Song
Kawagoe, Shiho
Ohashi, Toya
Brady, Roscoe O.
Eto, Yoshikatsu
TI Induced pluripotent stem cells derived from mouse models of lysosomal
storage disorders
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cardiomyocyte; embryoid body; neural stem cell
ID MUCOPOLYSACCHARIDOSIS TYPE-VII; BETA-GLUCURONIDASE DEFICIENCY;
FABRY-DISEASE; ALPHA-GALACTOSIDASE; ENZYME REPLACEMENT; HUMAN
FIBROBLASTS; DIFFERENTIATION; BRAIN; TRANSPLANTATION; EXPRESSION
AB Most lysosomal storage diseases (LSDs) are life-threatening genetic diseases. The pathogenesis of these diseases is poorly understood. Induced pluripotent stem (iPS) cell technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here we report the generation of disease-specific iPS cells from mouse models of Fabry disease, globoid cell leukodystrophy (GLD), and mucopolysaccharidosis VII (MPSVII). These mouse model-derived iPS cells showed defects in disease-specific enzyme activities and significant accumulation of substrates for these enzymes. In the lineage-directed differentiation studies, Fabry-iPS and GLD-iPS cells were efficiently differentiated into disease-relevant cell types, such as cardiomyocytes and neural stem cells, which might be useful in mechanistic and therapeutic studies. Notably, MPSVII-iPS cells demonstrated a markedly impaired ability to form embryoid bodies (EBs) in vitro. MPSVII-EBs exibited elevated levels of hyaluronan and its receptor CD44, and markedly reduced expression levels of E-cadherin and cell-proliferating marker. Partial correction of enzyme deficiency in MSPVII-iPS cells led to improved EB formation and reversal of aberrant protein expression. These data indicate a potential mechanism for the partial lethality of MPSVII mice in utero, and suggest a possible abnormality of embryonic development in MPSVII patients. Thus, our study demonstrates the unique promise of iPS cells for studying the pathogenesis and treatment of LSDs.
C1 [Meng, Xing-Li; Shen, Jin-Song; Ohashi, Toya] Jikei Univ, Sch Med, Dept Gene Therapy, Tokyo 1058461, Japan.
[Meng, Xing-Li; Shen, Jin-Song; Kawagoe, Shiho; Ohashi, Toya; Eto, Yoshikatsu] Jikei Univ, Sch Med, Dept Genet Dis & Genome Sci, Tokyo 1058461, Japan.
[Brady, Roscoe O.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Shen, JS (reprint author), Baylor Res Inst, Inst Metab Dis, Dallas, TX 75226 USA.
EM jinsong.shen@baylorhealth.edu; bradyr@ninds.nih.gov
FU Jikei University Research Fund; Japan Society for the Promotion of
Science; Research for Intractable Diseases from the Japanese Ministry of
Health, Welfare, and Labor
FX We thank Dr. Toshio Kitamura (University of Tokyo) for providing the
Plat-E packaging cell line (37), Y. Kurahashi (Seikagaku Corp) for
performing the HPLC analysis of hyaluronan, and E. Kikuchi (Jikei
University) for helping with the confocal laser microscopy. We also
thank Dr. Raphael Schiffmann (Institute of Metabolic Disease, Baylor
Research Institute) for comments on and critical editing of the
manuscript. This work was supported by the Jikei University Research
Fund, a Grant-in-Aid for Young Scientists from the Japan Society for the
Promotion of Science, and a Grant for Research for Intractable Diseases
from the Japanese Ministry of Health, Welfare, and Labor.
NR 37
TC 26
Z9 28
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 27
PY 2010
VL 107
IS 17
BP 7886
EP 7891
DI 10.1073/pnas.1002758107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 588QQ
UT WOS:000277088700052
PM 20385825
ER
PT J
AU de Azua, IR
Scarselli, M
Rosemond, E
Gautam, D
Jou, W
Gavrilova, O
Ebert, PJ
Levitt, P
Wess, J
AF de Azua, Inigo Ruiz
Scarselli, Marco
Rosemond, Erica
Gautam, Dinesh
Jou, William
Gavrilova, Oksana
Ebert, Philip J.
Levitt, Pat
Wess, Juergen
TI RGS4 is a negative regulator of insulin release from pancreatic
beta-cells in vitro and in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE knockout mice; muscarinic receptor; RGS proteins; G protein-coupled
receptor
ID G-PROTEIN SIGNALING-4; MUSCARINIC ACETYLCHOLINE-RECEPTORS; CHROMOSOME
TRANSGENIC ANALYSIS; DYNAMIC EXPRESSION PATTERNS; GLUCOSE-HOMEOSTASIS;
MESSENGER-RNA; DRUG TARGETS; MECHANISMS; SECRETION; STIMULATION
AB Therapeutic strategies that augment insulin release from pancreatic beta-cells are considered beneficial in the treatment of type 2 diabetes. We previously demonstrated that activation of beta-cell M-3 muscarinic receptors (M3Rs) greatly promotes glucose-stimulated insulin secretion (GSIS), suggesting that strategies aimed at enhancing signaling through beta-cell M3Rs may become therapeutically useful. M3R activation leads to the stimulation of G proteins of the G(q) family, which are under the inhibitory control of proteins known as regulators of G protein signaling (RGS proteins). At present, it remains unknown whether RGS proteins play a role in regulating insulin release. To address this issue, we initially demonstrated that MIN6 insulinoma cells express functional M3Rs and that RGS4 was by far the most abundant RGS protein expressed by these cells. Strikingly, siRNA-mediated knockdown of RGS4 expression in MIN6 cells greatly enhanced M3R-mediated augmentation of GSIS and calcium release. We obtained similar findings using pancreatic islets prepared from RGS4-deficient mice. Interestingly, RGS4 deficiency had little effect on insulin release caused by activation of other beta-cell GPCRs. Finally, treatment of mutant mice selectively lacking RGS4 in pancreatic beta-cells with a muscarinic agonist (bethanechol) led to significantly increased plasma insulin and reduced blood glucose levels, as compared to control littermates. Studies with beta-cell-specific M3R knockout mice showed that these responses were mediated by beta-cell M3Rs. These findings indicate that RGS4 is a potent negative regulator of M3R function in pancreatic beta-cells, suggesting that RGS4 may represent a potential target to promote insulin release for therapeutic purposes.
C1 [de Azua, Inigo Ruiz; Scarselli, Marco; Rosemond, Erica; Gautam, Dinesh; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Jou, William; Gavrilova, Oksana] NIDDKD, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA.
[Ebert, Philip J.; Levitt, Pat] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA.
RP Wess, J (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
OI Scarselli, Marco/0000-0001-5087-3182
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health; Department of Health and Human Services;
Basque Government
FX This work was supported by the Intramural Research Program, National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Department of Health and Human Services. We thank
Ms. Yinghong Cui (National Institute of Diabetes and Digestive and
Kidney Diseases) for excellent technical assistance and Dr. Susanne M.
Mumby (University of Texas Southwestern Medical Center) for providing
the antiRGS4 antibody. I. R. A. was the recipient of a Basque Government
Fellowship.
NR 38
TC 34
Z9 34
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 27
PY 2010
VL 107
IS 17
BP 7999
EP 8004
DI 10.1073/pnas.1003655107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 588QQ
UT WOS:000277088700071
ER
PT J
AU Largent, EA
Wendler, D
Emanuel, E
Miller, FG
AF Largent, Emily A.
Wendler, David
Emanuel, Ezekiel
Miller, Franklin G.
TI Is Emergency Research Without Initial Consent Justified? The Consent
Substitute Model
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID INFORMED-CONSENT; CLINICAL-RESEARCH; COMMUNITY CONSULTATION;
RESUSCITATION RESEARCH; EUROPEAN-UNION; CARE RESEARCH; EXCEPTION;
SETTINGS; ETHICS; TRAUMA
AB Emergency research poses a fundamental ethical dilemma: prohibit valuable research because informed consent is not possible or enroll individuals in clinical trials without informed consent. Although emergency research without initial consent is allowable in the United States, its regulatory status remains uncertain internationally. More important, no ethical justification for emergency research without consent has been widely accepted. Whether emergency research without initial consent can be justified depends on whether the values that are secured by informed consent-respect for autonomy and protection of well-being can be secured by other means. Analysis suggests that these values can be secured by the satisfaction of 5 conditions: (1) responsiveness (the experimental intervention must be responsive to an urgent medical need of the patients), (2) comparable risk-benefit ratio (the risk-benefit ratio of the experimental intervention is favorable, and at least as favorable as that of available alternatives and the control, if any), (3) no conflicting preferences (there is no compelling reason to think that participation in the research conflicts with enrolled patients' values or interests), (4) minimal net risks (nonbeneficial procedures included in the study cumulatively pose no greater than minimal risk), and (5) prompt consent (consent for ongoing and additional emergency research interventions is obtained as soon as possible). Together, these conditions constitute an ethical substitute for informed consent in emergency research-forming the consent substitute model. Arch Intern Med. 2010; 170(8): 668-674
C1 [Largent, Emily A.; Wendler, David; Emanuel, Ezekiel; Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 41
TC 15
Z9 15
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 26
PY 2010
VL 170
IS 8
BP 668
EP 674
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 588JD
UT WOS:000277064800002
PM 20421549
ER
PT J
AU Muller-Riemenschneider, F
Holmberg, C
Rieckmann, N
Kliems, H
Rufer, V
Muller-Nordhorn, J
Willich, SN
AF Mueller-Riemenschneider, Falk
Holmberg, Christine
Rieckmann, Nina
Kliems, Harald
Rufer, Veronika
Mueller-Nordhorn, Jacqueline
Willich, Stefan N.
TI Barriers to Routine Risk-Score Use for Healthy Primary Care Patients
Survey and Qualitative Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE RISK; CORONARY-HEART-DISEASE; PREDICTION;
VALIDATION; FRAMINGHAM; COHORT; GUIDELINES; DERIVATION; WOMEN
AB Background: Risk scores for the primary prevention of chronic diseases in healthy adults are frequently recommended but often underused by general practitioners (GPs). The objectives of this study were to assess the use of and attitudes regarding the use of risk scores among GPs and to identify possible barriers to use.
Methods: Between November 7, 2007, and April 4, 2008, 68 GPs in Berlin, Germany, participated in the survey, and 24 were additionally invited to participate in focus groups. Quantitative data were analyzed descriptively and qualitative data were analyzed according to grounded theory.
Results: Survey data of 42 GPs indicated that physicians regularly perform risk assessments for healthy patients, although most did not use risk scores. The usefulness of risk scores was rated largely positive. Focus groups revealed some confusion about the definition of risk scores and that participants resisted general use. Barriers to risk-score use were lack of lifestyle recommendations, regulatory constraints, the patient's role, and lack of accuracy. Suggestions for improvement included computerized risk prediction for multiple diseases simultaneously, better computer-generated visual presentation, and the integration of lifestyle recommendations.
Conclusions: The GPs perceive the routine use of risk scores as infeasible because of regulatory constraints and the nature of the physician-patient relationship. These factors need to be considered to increase risk-score use. Training of physicians could also help somewhat to overcome underuse. Use of computerized approaches that enable the prediction of risks for several chronic diseases simultaneously and improved computer-generated visual presentation may increase acceptance. Risk profiles should further be related to recommendations for health-behavior modification.
C1 [Mueller-Riemenschneider, Falk; Willich, Stefan N.] Charite Univ Med Ctr Berlin, Inst Social Med Epidemiol & Hlth Econ, D-10098 Berlin, Germany.
[Rieckmann, Nina; Mueller-Nordhorn, Jacqueline] Charite Univ Med Ctr Berlin, Berlin Sch Publ Hlth, D-10098 Berlin, Germany.
[Rufer, Veronika] Charite Univ Med Ctr Berlin, Inst Primary Hlth Care, D-10098 Berlin, Germany.
[Holmberg, Christine] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rieckmann, Nina] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Kliems, Harald] Cornell Univ, Dept Sci & Technol Studies, Ithaca, NY USA.
RP Muller-Riemenschneider, F (reprint author), Charite Univ Med Ctr Berlin, Inst Social Med Epidemiol & Hlth Econ, Luisenstr 57, D-10098 Berlin, Germany.
EM Falk.Mueller-Riemenschneider@charite.de
FU Allgemeine Ortskrankenkassen Berlin
FX This study was funded in part by Allgemeine Ortskrankenkassen Berlin
(statutory health insurance organization).
NR 32
TC 26
Z9 26
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 26
PY 2010
VL 170
IS 8
BP 719
EP 724
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 588JD
UT WOS:000277064800010
PM 20421559
ER
PT J
AU Abente, EJ
Sosnovtsev, SV
Bok, K
Green, KY
AF Abente, Eugenio J.
Sosnovtsev, Stanislav V.
Bok, Karin
Green, Kim Y.
TI Visualization of feline calicivirus replication in real-time with
recombinant viruses engineered to express fluorescent reporter proteins
SO VIROLOGY
LA English
DT Article
DE Feline calicivirus; Transposon mutagenesis; Recombinant; Replication;
Gene expression
ID OPEN READING FRAMES; NORWALK VIRUS; CAPSID PROTEIN; INFECTED-CELLS;
NONSTRUCTURAL POLYPROTEIN; STABLE EXPRESSION; PRECURSOR PROTEIN; TN7
TRANSPOSITION; MURINE NOROVIRUS; GENETIC-ANALYSIS
AB Caliciviruses are non-enveloped, icosahedral viruses with a single-stranded, positive sense RNA genome. Transposon-mediated insertional mutagenesis was used to insert a transprimer sequence into random sites of an infectious full-length cDNA clone of the feline calicivirus (FCV) genome. A site in the LC gene (encoding the capsid leader protein) of the FCV genome was identified that could tolerate foreign insertions, and two viable recombinant FCV variants expressing LC fused either to AcGFP, or DsRedFP were recovered. The effects of the insertions on LC processing, RNA replication, and stability of the viral genome were analyzed, and the progression of a calicivirus single infection and co-infection were captured by real-time imaging fluorescent microscopy. The ability to engineer viable recombinant caliciviruses expressing foreign markets enables new approaches to investigate virus and host cell interactions, as well as studies of viral recombination, one of the driving forces of calicivirus evolution. Published by Elsevier Inc.
C1 [Green, Kim Y.] NIAID, Norovirus Gastroenteritis Unit, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Abente, Eugenio J.; Green, Kim Y.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
RP Green, KY (reprint author), NIAID, Norovirus Gastroenteritis Unit, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Room 6318, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
OI Abente, Eugenio/0000-0002-3390-2786
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 102
TC 6
Z9 7
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD APR 25
PY 2010
VL 400
IS 1
BP 18
EP 31
DI 10.1016/j.virol.2009.12.035
PG 14
WC Virology
SC Virology
GA 571OY
UT WOS:000275764900003
PM 20137802
ER
PT J
AU Checkley, MA
Luttge, BG
Soheilian, F
Nagashima, K
Freed, EO
AF Checkley, Mary Ann
Luttge, Benjamin G.
Soheilian, Ferri
Nagashima, Kunio
Freed, Eric O.
TI The capsid-spacer peptide 1 Gag processing intermediate is a
dominant-negative inhibitor of HIV-1 maturation
SO VIROLOGY
LA English
DT Article
DE HIV-1; Gag; Virus maturation; Assembly; Retrovirus; Protease
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 GAG; PARTICLE MATURATION; HELICAL
STRUCTURE; VIRAL PROTEASE; CLEAVAGE SITES; LIFE-CYCLE; AMINO-ACID;
POLYPROTEIN; CORE
AB The human immunodeficiency virus type 1 (HIV-1) maturation inhibitor bevirimat disrupts virus replication by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) Gag processing intermediate to mature CA. The observation that bevirimat delays but does not completely block CA-SP1 processing suggests that the presence of uncleaved CA-SP1 may disrupt the maturation process in trans. In this study, we validate this hypothesis by using a genetic approach to demonstrate that a non-cleavable CA-SP1 Mutant exerts a dominant-negative effect on Maturation of wild-type HIV-1. In contrast, a mutant in which cleavage can occur internally within SP1 is significantly less potent as a dominant-negative inhibitor. We also show that bevirimat blocks processing at both the major CA-SP1 cleavage site and the internal site. These data underscore the importance of full CA-SP1 processing for HIV-1 maturation and highlight the therapeutic potential of inhibitors that target this Gag cleavage event. Published by Elsevier Inc.
C1 [Checkley, Mary Ann; Luttge, Benjamin G.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Soheilian, Ferri; Nagashima, Kunio] NCI, Image Anal Lab, Res Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108,1050 Boyles St, Frederick, MD 21702 USA.
EM efreed@nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH
[N01-CO-12400]; Intramural AIDS Targeted Antiviral Program
FX We thank members of the Freed laboratory for helpful discussion and
critical review of the manuscript. We thank H.-G. Krjusslich for
providing the CA5 mutant and S.-K. Lee and R. Swanstrom for the L3631
mutant. We thank C. Adamson and E. Chertova for sharing unpublished
data. The HIV-Ig and TZM-bl cells were obtained from the NIH AIDS
Research and Reference Reagent Program. This research was supported by
the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, NIH, and by the Intramural AIDS Targeted
Antiviral Program. This project was funded in part with federal funds
from the National Cancer Institute, NIH, under contract N01-CO-12400.
NR 36
TC 29
Z9 29
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 0042-6822
J9 VIROLOGY
JI Virology
PD APR 25
PY 2010
VL 400
IS 1
BP 137
EP 144
DI 10.1016/j.virol.2010.01.028
PG 8
WC Virology
SC Virology
GA 571OY
UT WOS:000275764900014
PM 20172577
ER
PT J
AU Nemes, E
Bertoncelli, L
Lugli, E
Pinti, M
Nasi, M
Manzini, L
Manzini, S
Prati, F
Borghi, V
Cossarizza, A
Mussini, C
AF Nemes, Elisa
Bertoncelli, Linda
Lugli, Enrico
Pinti, Marcello
Nasi, Milena
Manzini, Lisa
Manzini, Serena
Prati, Francesca
Borghi, Vanni
Cossarizza, Andrea
Mussini, Cristina
TI Cytotoxic granule release dominates gag-specific CD4(+) T-cell response
in different phases of HIV infection
SO AIDS
LA English
DT Article
DE AIDS; CD107a; CD154; CD4; gag; HIV; long-term nonprogressor; lymphocyte
degranulation; specific response
ID IMMUNODEFICIENCY-VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; CD40 LIGAND;
TREATMENT INTERRUPTION; EFFECTOR FUNCTIONS; IMMUNE-RESPONSES; TYPE-1
INFECTION; VIRAL LOAD; VIREMIA; LYMPHOCYTES
AB Background: The activity of virus-specific T lymphocytes, among which those capable of a polyfunctional response against the viral protein gag, is crucial to control HIV infection.
Objective: The objective of this study is to investigate the polyfunctionality of gag-specific T cells in different phases of HIV infection, analyzing markers related to T-helper cell 1 (Th1) and degranulation/cytotoxicity, and the production of Th1 cytokines in peripheral blood lymphocytes from patients experiencing an acute primary infection, long-term nonprogressors, patients naive for antiretroviral drugs, and patients taking HAART.
Materials and methods: Cells were stimulated with a pool of gag-derived peptides or with a superantigen (staphylococcal enterotoxin B). Using eight-color polychromatic flow cytometry, we analyzed the expression of interleukin-2, interferon-gamma, CD154, and CD107a by CD4(+) and CD8(+) T cells.
Results: The main finding was that in all HIV-positive patients, about half gag-specific CD4(+) T cells were CD107a(+), that is, able to degranulate. CD4(+)CD154(+) cells unable to produce Th1 cytokines were the second most represented population. Truly polyfunctional CD4(+) T cells were very rare and present only in a few long-term nonprogressors. Superantigen stimulation showed that CD4(+) T lymphocytes from all patients displayed a typical Th response, including interleukin-2 and interferon-gamma production, lacking CD107a expression.
Conclusion: In all the aforementioned phases of HIV infection, the large majority of gag-specific CD4(+) T lymphocytes cannot be identified by the sole expression of interleukin-2 and interferon-gamma, which is early impaired. Degranulation and helper functions other than Th1 cytokine production are the predominant features of HIV-specific CD4(+) lymphocytes. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Nemes, Elisa; Bertoncelli, Linda; Lugli, Enrico; Pinti, Marcello; Nasi, Milena; Manzini, Serena; Cossarizza, Andrea] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41125 Modena, Italy.
[Lugli, Enrico] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH Bethesda, Bethesda, MD USA.
[Manzini, Lisa; Prati, Francesca; Borghi, Vanni; Mussini, Cristina] Azienda Osped Univ, Infect Dis Clin, Modena, Italy.
RP Cossarizza, A (reprint author), Univ Modena & Reggio Emilia, Dept Biomed Sci, Via Campi 287, I-41125 Modena, Italy.
EM andrea.cossarizza@unimore.it
RI Pinti, Marcello/C-9351-2015; Nasi, Milena/J-4425-2016;
OI Pinti, Marcello/0000-0001-9118-1262; Nasi, Milena/0000-0003-3079-8001;
Cossarizza, Andrea/0000-0002-5381-1558
FU Istituto Superiore di Sanita, Rome, Italy [40G.62]
FX This study was partially supported by the 'Concerted Action ELVIS:
Evaluation of Long term Non Progressors: Viro-Immunological Study', in
the framework of the Progetto Nazionale AIDS 2007 - Istituto Superiore
di Sanita, Rome, Italy (grant 40G.62 to A. C.). We gratefully
acknowledge Partec GmbH (Munster, Germany) and Space srl (Milan, Italy)
for continuous technical support. We thank Dr. M. M. Lederman (Case
Western Reserve Univ., Cleveland, OH) for helpful suggestions.
NR 58
TC 27
Z9 27
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD APR 24
PY 2010
VL 24
IS 7
BP 947
EP 957
DI 10.1097/QAD.0b013e328337b144
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 582AN
UT WOS:000276567500002
PM 20179574
ER
PT J
AU Wong, HL
Breen, EC
Pfeiffer, RM
Aissani, B
Martinson, JJ
Margolick, JB
Kaslow, RA
Jacobson, LP
Ambinder, RF
Chanock, S
Martinez-Maza, O
Rabkin, CS
AF Wong, Hui-Lee
Breen, Elizabeth C.
Pfeiffer, Ruth M.
Aissani, Brahim
Martinson, Jeremy J.
Margolick, Joseph B.
Kaslow, Richard A.
Jacobson, Lisa P.
Ambinder, Richard F.
Chanock, Stephen
Martinez-Maza, Otoniel
Rabkin, Charles S.
TI Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin
lymphoma risk in the multicenter AIDS cohort study
SO AIDS
LA English
DT Article
DE AIDS-related lymphoma; cytokine; single-nucleotide polymorphisms
ID EPSTEIN-BARR-VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NERVOUS-SYSTEM
LYMPHOMA; INTERLEUKIN-10; INFECTION; PROMOTER; IL10; EXPRESSION; IL-10;
CELLS
AB Background: Cytokine stimulation of B-cell proliferation may be an important causative mechanism for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). The Epstein-Barr virus (EBV) may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine-signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors.
Patients and materials: We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N = 160) or post-AIDS diagnosis (N = 90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR = 0.3; 95% CI 0.1, 0.7) but not systemically (CC vs. CT/TT: OR = 1.0; 95% CI 0.5, 1.9) (P(heterogeneity) = 0.03). Carriage of two copies of the 'low IL10' haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (P(trend) = 0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0.
Conclusion: Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important causative pathway for EBV-related lymphomagenesis. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Wong, Hui-Lee; Pfeiffer, Ruth M.; Chanock, Stephen; Rabkin, Charles S.] NCI, Rockville, MD USA.
[Breen, Elizabeth C.; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Aissani, Brahim; Kaslow, Richard A.] Univ Alabama, Birmingham, AL USA.
[Martinson, Jeremy J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Margolick, Joseph B.; Jacobson, Lisa P.; Ambinder, Richard F.] Johns Hopkins Univ, Baltimore, MD USA.
RP Wong, HL (reprint author), Ctr Devices & Radiol Hlth, Div Epidemiol, Off Surveillance & Biometr, FDA WO66-4561,10903 New Hampshire Av, Silver Spring, MD 20993 USA.
EM huilee.wong@fda.hhs.gov
RI Pfeiffer, Ruth /F-4748-2011; Ambinder, Richard/G-1607-2011;
Martinez-Maza, Otoniel/B-2667-2009;
OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Martinson,
Jeremy/0000-0003-4673-7238
FU National Cancer Institute, National Institutes of Health; NIH
[R01-CA73475, R01-CA57152, P50-CA-096888]; National Institute of Allergy
and Infectious Diseases; National Heart, Lung and Blood Institute
FX The study was funded in part by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. This work was
supported, in part, by grants from the NIH (R01-CA73475, R01-CA57152,
P50-CA-096888). Data in this manuscript were collected by the
Multicenter AIDS Cohort Study (MACS) with centers (Principal
Investigators) at The Johns Hopkins University Bloomberg School of
Public Health (Joseph B. Margolick, Lisa Jacobson), Howard Brown Health
Center and Northwestern University Medical School (John Phair),
University of California, Los Angeles (Roger Detels), and University of
Pittsburgh (Charles Rinaldo). The MACS is funded by the National
Institute of Allergy and Infectious Diseases, with additional
supplemental funding from the National Cancer Institute and the National
Heart, Lung and Blood Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC),
UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613,
UO1-AI-35041. Website located at
http://www.statepi.jhsph.edu/macs/macs.html.
NR 34
TC 22
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD APR 24
PY 2010
VL 24
IS 7
BP 1025
EP 1033
DI 10.1097/QAD.0b013e328332d5b1
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 582AN
UT WOS:000276567500012
PM 20299965
ER
PT J
AU Tramont, EC
AF Tramont, Edmund C.
TI The fidelity of decision-making: the Achilles heel for the successful
implementation of prevention modalities for HIV
SO AIDS
LA English
DT Letter
C1 DCR NIAID NIH, Bethesda, MD 20814 USA.
RP Tramont, EC (reprint author), DCR NIAID NIH, 6700 Rockledge Dr, Bethesda, MD 20814 USA.
EM et89f@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD APR 24
PY 2010
VL 24
IS 7
BP 1077
EP 1078
DI 10.1097/QAD.0b013e32832f74cd
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 582AN
UT WOS:000276567500023
PM 20386377
ER
PT J
AU Dahut, WL
Madan, RA
AF Dahut, William L.
Madan, Ravi A.
TI Revisiting the ultimate target of treatment for prostate cancer
SO LANCET
LA English
DT Editorial Material
ID ANTIANDROGEN WITHDRAWAL; ABIRATERONE ACETATE; MITOXANTRONE; PREDNISONE;
ANDROGEN; DOCETAXEL; TRIAL; CYP17
C1 [Dahut, William L.; Madan, Ravi A.] NCI, Div Clin Sci, Bethesda, MD 20892 USA.
RP Dahut, WL (reprint author), NCI, Div Clin Sci, Bethesda, MD 20892 USA.
EM dahutw@mail.nih.gov
NR 11
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 0140-6736
J9 LANCET
JI Lancet
PD APR 24
PY 2010
VL 375
IS 9724
BP 1409
EP 1410
DI 10.1016/S0140-6736(10)60400-X
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 590FL
UT WOS:000277210000004
PM 20398924
ER
PT J
AU Goldenberg, RL
McClure, EM
Saleem, S
Reddy, UM
AF Goldenberg, Robert L.
McClure, Elizabeth M.
Saleem, Sarah
Reddy, Uma M.
TI Infection-related stillbirths
SO LANCET
LA English
DT Review
ID PARVOVIRUS B19 INFECTION; INTRAUTERINE FETAL-DEATH; BORNE RELAPSING
FEVER; CONGENITAL-RUBELLA SYNDROME; MATERNAL RISK-FACTORS; SUB-SAHARAN
AFRICA; DEVELOPING-COUNTRIES; PREGNANT-WOMEN; HISTOLOGIC
CHORIOAMNIONITIS; ANTIRETROVIRAL THERAPY
AB Infection is an important cause of stillbirths worldwide: in low-income and middle-income countries, 50% of stillbirths or more are probably caused by infection. By contrast, in high-income countries only 10-25% of stillbirths are caused by infection. Syphilis, where prevalent, causes most infectious stillbirths, and is the infection most amenable to screening and treatment. Ascending bacterial infection is a common cause of stillbirths, but prevention has proven elusive. Many viral infections cause stillbirths but aside from vaccination for common childhood diseases, we do not have a clear prevention strategy. Malaria, because of its high prevalence and extensive placental damage, accounts for large numbers of stillbirths. Intermittent malarial prophylaxis and insecticide-treated bednets should decrease stillbirths. Many infections borne by animals and vectors cause stillbirths, and these types of infections occur frequently in low-income countries. Research that better defines the relation between these infections and stillbirths, and develops strategies to reduce associated adverse outcomes, should play an important part in reduction of stillbirths in low-income countries.
C1 [Goldenberg, Robert L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19102 USA.
[McClure, Elizabeth M.] Univ N Carolina, Chapel Hill, NC USA.
[McClure, Elizabeth M.] Res Triangle Inst, Durham, NC USA.
[Saleem, Sarah] Aga Khan Univ, Karachi, Pakistan.
[Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Goldenberg, RL (reprint author), Drexel Univ, Coll Med, Dept Obstet & Gynecol, 245 N 15th St,17th Floor,Room 17113, Philadelphia, PA 19102 USA.
EM rgoldenb@drexelmed.edu
FU National Institute of Child Health and Human Development Global Network
FX RLG, EMM, and SS are funded by grants from the National Institute of
Child Health and Human Development Global Network.
NR 108
TC 49
Z9 50
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD APR 24
PY 2010
VL 375
IS 9724
BP 1482
EP 1490
DI 10.1016/S0140-6736(09)61712-8
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 590FL
UT WOS:000277210000034
PM 20223514
ER
PT J
AU Rao, SS
Mohan, KVK
Nguyen, N
Abraham, B
Abdouleva, G
Zhang, P
Atreya, CD
AF Rao, Shilpakala Sainath
Mohan, Ketha V. K.
Nguyen, Nga
Abraham, Bindu
Abdouleva, Galina
Zhang, Pei
Atreya, Chintamani D.
TI Peptides panned from a phage-displayed random peptide library are useful
for the detection of Bacillus anthracis surrogates B. cereus 4342 and B.
anthracis Sterne
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Bacillus anthracis; Counter-terrorism; Peptide ligands; Phage-display;
Plasma; Quantum dots
ID SPORES; DISCOVERY; THURINGIENSIS; ANTIBODIES; LIGANDS; PROBES; CELLS
AB Recent use of Bacillus anthracis as a bioweapon has highlighted the need for a sensitive monitoring system. Current bacterial detection tests use antibodies as bio-molecular recognition elements which have limitations with regard to time, specificity and sensitivity, creating the need for new and improved cost-effective high-affinity detection probes. In this study, we screened a commercially available bacteriophage-displayed random peptide library using Bacillus cereus 4342 cells as bait to identify peptides that could be used for detection of Bacillus. The method enabled us to identify two 12-amino acid consensus peptide sequences that specifically bind to B. cereus 4342 and B. anthracis Sterne, the nonpathogenic surrogates of B. anthracis strain. The two Bacillus-binding peptides (named BBP-1 and BBP-2) were synthesized with biotin tag to confirm their binding by four independent detection assays. Dot-blot analysis revealed that the peptides bind specifically to B. cereus 4342 and B. anthracis Sterne. Quantitative analysis of this interaction by ELISA and fluorometry demonstrated a detection sensitivity of 102 colony forming U/ml (CFU/ml) by both assays. When the peptides were used in combination with Qdots, the sensitivity was enhanced further by enabling detection of even a single bacterium by fluorescence microscopy. Immunoblot analysis and protein sequencing showed that BBP-1 and BBP-2 bound to the S-layer protein of B. anthracis Sterne. Overall, our findings validate the usefulness of synthetic versions of phage-derived peptides in combination with Qdot-liquid nanocrystals as high sensitivity bioprobes for various microbial detection platforms. Published by Elsevier Inc.
C1 [Rao, Shilpakala Sainath; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Nguyen, Nga; Abdouleva, Galina] US FDA, Facil Biotechnol Resources, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Abraham, Bindu] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Zhang, Pei] US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Mohan, KVK (reprint author), US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bldg 29A,Room 2C-15,HFM 335,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA.
EM krishna.ketha@fda.hhs.gov
FU Biomedical Advanced Research Development Authority (BARDA); Center for
Biologics Evaluation and Research (CBER)
FX This work was partially supported by Biomedical Advanced Research
Development Authority (BARDA) funds to C.A. S.S. is a recipient of a
postdoctoral fellowship at the Center for Biologics Evaluation and
Research (CBER) administered by the Oak Ridge Institute for Science and
Education (ORISE) through an intra agency agreement between the U.S.
Department of Energy and the U.S. Food and Drug Administration. Authors
thank Drs. Xuan Chi and Mikhail Ovanesov, OBRR, CBER for their review of
the manuscript.
NR 31
TC 4
Z9 4
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD APR 23
PY 2010
VL 395
IS 1
BP 93
EP 98
DI 10.1016/j.bbrc.2010.03.145
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 591JZ
UT WOS:000277298000018
ER
PT J
AU Yagi, R
Junttila, IS
Wei, G
Urban, JF
Zhao, KJ
Paul, WE
Zhu, JF
AF Yagi, Ryoji
Junttila, Ilkka S.
Wei, Gang
Urban, Joseph F., Jr.
Zhao, Keji
Paul, William E.
Zhu, Jinfang
TI The Transcription Factor GATA3 Actively Represses RUNX3
Protein-Regulated Production of Interferon-gamma
SO IMMUNITY
LA English
DT Article
ID HELPER TYPE-1 CELLS; CD4(+) T-CELLS; TH2 DIFFERENTIATION; LINEAGE
COMMITMENT; BET; EXPRESSION; RESPONSES; STAT4; GENE; SIGNALS
AB The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma. Such IFN-gamma production was transcription factor T-bet independent. Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production. GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein. Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells. Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner.
C1 [Yagi, Ryoji; Junttila, Ilkka S.; Paul, William E.; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wei, Gang; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Urban, Joseph F., Jr.] USDA, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Wei, Gang/A-3291-2011; Zhu, Jinfang/B-7574-2012
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Division of Intramural Research, National Heart
Lung and Blood Institute, National Institutes of Health, USA
FX We thank N Killeen for providing dLck-Cre transgenic mice (line 3779), I
Taniuchi and D R Littman for providing anti-CBF beta and
Runxfl/fl mice, S L Reiner for providing Eomes-GFP-RV and
T-bet DN-GFP-RV, R A Flavell for providing Thy1 1-RV, T Egawa for both
providing Runx antibody and for helpful discussion, S Tanksley, C
Eigsti, and J Edwards for cell sorting, and T Nakayama, D Jankovic, N
Takemoto, and H Yamane for their helpful discussions We also thank J J
O'Shea and P L Schwartzberg for critical reading of the manuscript The
work is supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases and the Division of
Intramural Research, National Heart Lung and Blood Institute, National
Institutes of Health, USA
NR 43
TC 73
Z9 74
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD APR 23
PY 2010
VL 32
IS 4
BP 507
EP 517
DI 10.1016/j.immuni.2010.04.004
PG 11
WC Immunology
SC Immunology
GA 589RW
UT WOS:000277171900010
PM 20399120
ER
PT J
AU Berrigan, D
Pickle, LW
Dill, J
AF Berrigan, David
Pickle, Linda W.
Dill, Jennifer
TI Associations between street connectivity and active transportation
SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS
LA English
DT Article
ID PHYSICAL-ACTIVITY; US ADULTS; BUILT ENVIRONMENT; TRAVEL BEHAVIOR; URBAN
FORM; LAND-USE; WALKING; NEIGHBORHOOD; DESIGN; ZERO
AB Background: Past studies of associations between measures of the built environment, particularly street connectivity, and active transportation (AT) or leisure walking/bicycling have largely failed to account for spatial autocorrelation of connectivity variables and have seldom examined both the propensity for AT and its duration in a coherent fashion. Such efforts could improve our understanding of the spatial and behavioral aspects of AT. We analyzed spatially identified data from Los Angeles and San Diego Counties collected as part of the 2001 California Health Interview Survey.
Results: Principal components analysis indicated that similar to 85% of the variance in nine measures of street connectivity are accounted for by two components representing buffers with short blocks and dense nodes (PRIN1) or buffers with longer blocks that still maintain a grid like structure (PRIN2). PRIN1 and PRIN2 were positively associated with active transportation (AT) after adjustment for diverse demographic and health related variables. Propensity and duration of AT were correlated in both Los Angeles (r = 0.14) and San Diego (r = 0.49) at the zip code level. Multivariate analysis could account for the correlation between the two outcomes. After controlling for demography, measures of the built environment and other factors, no spatial autocorrelation remained for propensity to report AT (i.e., report of AT appeared to be independent among neighborhood residents). However, very localized correlation was evident in duration of AT, particularly in San Diego, where the variance of duration, after accounting for spatial autocorrelation, was 5% smaller within small neighborhoods (similar to 0.01 square latitude/longitude degrees = 0.6 mile diameter) compared to within larger zip code areas. Thus a finer spatial scale of analysis seems to be more appropriate for explaining variation in connectivity and AT.
Conclusions: Joint analysis of the propensity and duration of AT behavior and an explicitly geographic approach can strengthen studies of the built environment and physical activity (PA), specifically AT. More rigorous analytical work on cross-sectional data, such as in the present study, continues to support the need for experimental and longitudinal study designs including the analysis of natural experiments to evaluate the utility of environmental interventions aimed at increasing PA.
C1 [Berrigan, David] NCI, ARP, DCCPS, Bethesda, MD 20892 USA.
[Pickle, Linda W.] NCI, SRP, DCCPS, Bethesda, MD 20892 USA.
[Pickle, Linda W.] StatNet Consulting, Gaithersburg, MD USA.
[Pickle, Linda W.] Penn State Univ, University Pk, PA 16802 USA.
[Dill, Jennifer] Portland State Univ, Coll Urban & Publ Affairs, Portland, OR 97207 USA.
RP Berrigan, D (reprint author), NCI, ARP, DCCPS, Bethesda, MD 20892 USA.
EM berrigad@mail.nih.gov
RI Dill, Jennifer/D-5971-2011
OI Dill, Jennifer/0000-0001-5498-3928
NR 58
TC 45
Z9 45
U1 2
U2 22
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-072X
J9 INT J HEALTH GEOGR
JI Int. J. Health Geogr.
PD APR 23
PY 2010
VL 9
AR 20
DI 10.1186/1476-072X-9-20
PG 18
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 604IC
UT WOS:000278271700001
PM 20412597
ER
PT J
AU Landau, G
Bercovich, Z
Park, MH
Kahana, C
AF Landau, Guy
Bercovich, Zippi
Park, Myung Hee
Kahana, Chaim
TI The Role of Polyamines in Supporting Growth of Mammalian Cells Is
Mediated through Their Requirement for Translation Initiation and
Elongation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ORNITHINE-DECARBOXYLASE ANTIZYME; DEOXYHYPUSINE SYNTHASE; FACTOR 5A;
HYPUSINE MODIFICATION; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS;
MESSENGER-RNA; INHIBITION; EIF5A; YEAST
AB Polyamines are essential cell constituents whose depletion results in growth cessation. Here we have investigated potential mechanisms of action of polyamines in supporting mammalian cell proliferation. We demonstrate that polyamines regulate translation both at the initiation and at the elongation steps. L-alpha-Difluoromethylornithine treatment resulting in polyamine depletion reduces protein synthesis via inhibition of translation initiation. N1-Guanyl-diaminoheptane (GC7), a spermidine analogue that inhibits eukaryotic initiation factor 5A (eIF5A) hypusination, also caused inhibition of translation initiation. In contrast, depletion of eIF5A by short hairpin RNA inhibits translation elongation as was recently demonstrated in yeast and Drosophila. These results suggest that in addition to competing with spermidine in the hypusination reaction, GC7 also competes with spermidine at yet undefined sites required for translation initiation. Finally, we show that either polyamine depletion or GC7 treatment induced eIF2 alpha phosphorylation and reduced phosphorylation of 4E-BP, thus setting the molecular basis for the observed inhibition of translation initiation.
C1 [Landau, Guy; Bercovich, Zippi; Kahana, Chaim] Weizmann Inst Sci, Dept Mol Genet, IL-76199 Rehovot, Israel.
[Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Kahana, C (reprint author), Weizmann Inst Sci, Dept Mol Genet, IL-76199 Rehovot, Israel.
EM chaim.kahana@weizmann.ac.il
FU M. D. Moross Institute for Cancer Research; Israel Science Foundation
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was supported by a grant from the M. D. Moross
Institute for Cancer Research at the Weizmann Institute and by the
Israel Science Foundation.
NR 41
TC 43
Z9 45
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 23
PY 2010
VL 285
IS 17
BP 12474
EP 12481
DI 10.1074/jbc.M110.106419
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 584XO
UT WOS:000276787800003
PM 20181941
ER
PT J
AU Guo, XM
Williams, JG
Schug, TT
Li, XL
AF Guo, Xiumei
Williams, Jason G.
Schug, Thaddeus T.
Li, Xiaoling
TI DYRK1A and DYRK3 Promote Cell Survival through Phosphorylation and
Activation of SIRT1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-KINASE DYRK1A; SUBSTRATE-SPECIFICITY; TRANSCRIPTION FACTORS;
DEACETYLASE ACTIVITY; DUAL-SPECIFICITY; DNA-DAMAGE; STRESS; FAMILY;
REGULATOR; P53
AB DYRK1A (the dual specificity tyrosine phosphorylation-regulated kinase 1A) plays an important role in body growth and brain physiology. Overexpression of this kinase has been associated with the development of Down syndrome in both human and animal models, whereas single copy loss-of-function of DYRK1A leads to increased apoptosis and decreased brain size. Although more than a dozen of DYRK1A targets have been identified, the molecular basis of its involvement in neuronal development remains unclear. Here we show that DYRK1A and another pro-survival member of the DYRK family, DYRK3, promote cell survival through phosphorylation and activation of SIRT1, an NAD(+)-dependent protein deacetylase that is essential in a variety of physiological processes including stress response and energy metabolism. DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53. A SIRT1 phosphorylation mimetic (SIRT1 T522D) displays elevated deacetylase activity, thus inhibiting cell apoptosis. Conversely, a SIRT1 dephosphorylation mimetic (SIRT1 T522V) fails to mediate DYRK-induced deacetylation of p53 and cell survival. We show that knockdown of endogenous DYRK1A and DYRK3 leads to hypophosphorylation of SIRT1, sensitizing cells to DNA damage-induced cell death. We also provide evidence that phosphorylation of Thr(522) activates SIRT1 by promoting product release, thereby increasing its enzymatic turnover. Taken together, our findings provide a novel mechanism by which two anti-apoptotic DYRK members promote cell survival through direct modification of SIRT1. These findings may have important implications in understanding the molecular mechanisms of tumorigenesis, Down syndrome, and aging.
C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Williams, Jason G.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM lix3@niehs.nih.gov
FU National Institutes of Health [Z01 ES102205]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant Z01 ES102205 ( to X. L.).
NR 45
TC 96
Z9 102
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 23
PY 2010
VL 285
IS 17
BP 13223
EP 13232
DI 10.1074/jbc.M110.102574
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 584XO
UT WOS:000276787800077
PM 20167603
ER
PT J
AU Moir, S
Fauci, AS
AF Moir, Susan
Fauci, Anthony S.
TI IMMUNOLOGY Salmonella Susceptibility
SO SCIENCE
LA English
DT Editorial Material
ID HIV-INFECTION; ACTIVATION
C1 [Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov
NR 9
TC 7
Z9 9
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD APR 23
PY 2010
VL 328
IS 5977
BP 439
EP 440
DI 10.1126/science.1189088
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586YR
UT WOS:000276952400022
PM 20413482
ER
PT J
AU Kase, S
He, SK
Sonoda, S
Kitamura, M
Spee, C
Wawrousek, E
Ryan, SJ
Kannan, R
Hinton, DR
AF Kase, Satoru
He, Shikun
Sonoda, Shozo
Kitamura, Mizuki
Spee, Christine
Wawrousek, Eric
Ryan, Stephen J.
Kannan, Ram
Hinton, David R.
TI alpha B-crystallin regulation of angiogenesis by modulation of VEGF
SO BLOOD
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULAR MEMBRANES;
RETINAL-PIGMENT EPITHELIUM; MIMICKING PHOSPHORYLATION; MACULAR
DEGENERATION; APOPTOSIS; CELLS; EXPRESSION; PROTEINS; HYPOXIA
AB alpha B-crystallin is a chaperone belonging to the small heat shock protein family. Herein we show attenuation of intraocular angiogenesis in alpha B-crystallin knockout (alpha B-crystallin(-/-)) mice in 2 models of intraocular disease: oxygen-induced retinopathy and laser-induced choroidal neovascularization. Vascular endothelial growth factor A (VEGF-A) mRNA and hypoxia inducible factor-1 alpha protein expression were induced during retinal angiogenesis, but VEGF-A protein expression remained low in alpha B-crystallin(-/-) retina versus wild-type mice, whereas VEGF-R2 expression was not affected. Both alpha B-crystallin and its phosphorylated serine59 formwere expressed, and immunoprecipitation revealed alpha B-crystallin binding to VEGF-A but not transforming growth factor-beta in cultured retinal pigment epithelial (RPE) cells. alpha B-crystallin and VEGF-A are colocalized in the endoplasmic reticulum in RPE cells under chemical hypoxia. alpha B-crystallin(-/-) RPE showed low VEGF-A secretion under serum-starved conditions compared with wild-type cells. VEGF-A is polyubiquitinated in control and alpha B-crystallin siRNA treated RPE; however, mono-tetra ubiquitinated VEGF-A increases with alpha B-crystallin knockdown. Endothelial cell apoptosis in newly formed vessels was greater in alpha B-crystallin(-/-) than wild-type mice. Proteasomal inhibition in alpha B-crystallin(-/-) mice partially restores VEGF-A secretion and angiogenic phenotype in choroidal neovascularization. Our studies indicate an important role for alpha B-crystallin as a chaperone for VEGF-A in angiogenesis and its potential as a therapeutic target. (Blood. 2010; 115(16): 3398-3406)
C1 [Kase, Satoru; He, Shikun; Sonoda, Shozo; Kitamura, Mizuki; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Kase, Satoru; He, Shikun; Sonoda, Shozo; Kitamura, Mizuki; Ryan, Stephen J.; Kannan, Ram; Hinton, David R.] Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, Los Angeles, CA 90033 USA.
[Kase, Satoru; He, Shikun; Sonoda, Shozo; Kitamura, Mizuki; Spee, Christine; Ryan, Stephen J.; Kannan, Ram; Hinton, David R.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
[Wawrousek, Eric] NEI, DHHS, NIH, Bethesda, MD 20892 USA.
RP Hinton, DR (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, 2011 Zonal Ave,HMR 209, Los Angeles, CA 90033 USA.
EM dhinton@usc.edu
OI Kannan, Ram/0000-0002-1583-3414
FU Arnold and Mabel Beckman Foundation; Research to Prevent Blindness
(Doheny Eye Institute); National Institutes of Health [EY01545, EY03040]
FX This study was supported by the Arnold and Mabel Beckman Foundation
(DRH), Research to Prevent Blindness (Doheny Eye Institute), and
National Institutes of Health grants EY01545 and EY03040 (S.J.R., D. R.
H.).
NR 45
TC 79
Z9 84
U1 0
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 22
PY 2010
VL 115
IS 16
BP 3398
EP 3406
DI 10.1182/blood-2009-01-197095
PG 9
WC Hematology
SC Hematology
GA 586ZU
UT WOS:000276956500028
PM 20023214
ER
PT J
AU Rosand, J
Meschia, JF
Singleton, AB
AF Rosand, Jonathan
Meschia, James F.
Singleton, Andrew B.
CA Int Stroke Genetics Consortium
Wellcome Trust Case-Control Consor
TI Failure to Validate Association between 12p13 Variants and Ischemic
Stroke
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Meschia, James F.] Mayo Clin, Jacksonville, FL 32224 USA.
[Singleton, Andrew B.] NIA, Bethesda, MD 20892 USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Deloukas,
Panos/B-2922-2013; Ross, Owen/D-7573-2013; Matarin, Mar/F-1771-2016;
OI Deloukas, Panos/0000-0001-9251-070X; Matarin, Mar/0000-0002-4717-5735;
Jackson, Caroline/0000-0002-2067-2811; Jankowski,
Janusz/0000-0003-2130-9181
NR 3
TC 1
Z9 1
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 22
PY 2010
VL 362
IS 16
BP 1547
EP 1550
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 586GP
UT WOS:000276894700032
ER
PT J
AU Reynolds, SJ
Kityo, C
Hallahan, CW
Kabuye, G
Atwiine, D
Mbamanya, F
Ssali, F
Dewar, R
Daucher, M
Davey, RT
Mugyenyi, P
Fauci, AS
Quinn, TC
Dybul, MR
AF Reynolds, Steven J.
Kityo, Cissy
Hallahan, Claire W.
Kabuye, Geoffrey
Atwiine, Diana
Mbamanya, Frank
Ssali, Francis
Dewar, Robin
Daucher, Marybeth
Davey, Richard T., Jr.
Mugyenyi, Peter
Fauci, Anthony S.
Quinn, Thomas C.
Dybul, Mark R.
TI A Randomized, Controlled, Trial of Short Cycle Intermittent Compared to
Continuous Antiretroviral Therapy for the Treatment of HIV Infection in
Uganda
SO PLOS ONE
LA English
DT Article
ID TREATMENT INTERRUPTION STRATEGY; HUMAN-IMMUNODEFICIENCY-VIRUS;
DRUG-RESISTANCE; ADHERENCE; REGIMEN; PARAMETERS; LAMIVUDINE; STAVUDINE;
TOXICITY; FAILURE
AB Background: Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.
Methods: A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count >= 125 cells/mm(3) and HIV RNA plasma levels,50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.
Results: Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).
Conclusions: Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.
C1 [Reynolds, Steven J.; Hallahan, Claire W.; Daucher, Marybeth; Davey, Richard T., Jr.; Fauci, Anthony S.; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Kityo, Cissy; Kabuye, Geoffrey; Atwiine, Diana; Mbamanya, Frank; Ssali, Francis; Mugyenyi, Peter] Joint Clin Res Ctr, Kampala, Uganda.
[Dewar, Robin] NCI, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA.
[Dybul, Mark R.] Georgetown Univ, Ctr Law, ONeill Inst Natl & Global Hlth Law, Washington, DC USA.
[Dybul, Mark R.] George W Bush Inst, Dallas, TX USA.
RP Reynolds, SJ (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sjr@jhmi.edu
FU Laboratory of Immunoregulation, Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX The study was funded through the Laboratory of Immunoregulation,
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. SJR, CWH, MD, RTD,
ASF, TCQ & MAD were employees of the NIH during the study design and
implementation period and were involved in study design, conduct and
publication.
NR 32
TC 16
Z9 17
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 22
PY 2010
VL 5
IS 4
AR e10307
DI 10.1371/journal.pone.0010307
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586YT
UT WOS:000276952600024
PM 20442758
ER
PT J
AU Seenundun, S
Rampalli, S
Liu, QC
Aziz, A
Palii, C
Hong, SH
Blais, A
Brand, M
Ge, K
Dilworth, FJ
AF Seenundun, Shayesta
Rampalli, Shravanti
Liu, Qi-Cai
Aziz, Arif
Palii, Carmen
Hong, SunHwa
Blais, Alexandre
Brand, Marjorie
Ge, Kai
Dilworth, Francis Jeffrey
TI UTX mediates demethylation of H3K27me3 at muscle-specific genes during
myogenesis
SO EMBO JOURNAL
LA English
DT Article
DE chromatin; histone demethylase; myogenesis; transcription; UTX
ID RNA-POLYMERASE-II; CREATINE-KINASE ENHANCER; EMBRYONIC STEM-CELLS;
TAF(II)-CONTAINING COMPLEX; METHYLTRANSFERASE COMPLEX; TRANSCRIPTION
INITIATION; DROSOPHILA-MELANOGASTER; SIGNAL-TRANSDUCTION; REGULATORY
REGIONS; ACTIVE PROMOTERS
AB Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue-specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone H3-Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3-Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Interestingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene. The EMBO Journal (2010) 29, 1401-1411.doi: 10.1038/emboj.2010.37; Published online 18 March 2010
C1 [Seenundun, Shayesta; Rampalli, Shravanti; Liu, Qi-Cai; Aziz, Arif; Palii, Carmen; Brand, Marjorie; Dilworth, Francis Jeffrey] Ottawa Hosp Res Inst, Sprott Ctr Stem Cell Res, Regenerat Med Program, Ottawa, ON, Canada.
[Hong, SunHwa; Ge, Kai] NIDDK, NIH, Bethesda, MD USA.
[Blais, Alexandre] Univ Ottawa, Ottawa Inst Syst Biol, Dept Biochem Immunol & Microbiol, Ottawa, ON K1N 6N5, Canada.
[Brand, Marjorie; Dilworth, Francis Jeffrey] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1N 6N5, Canada.
RP Dilworth, FJ (reprint author), Ottawa Hlth Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, 501 Smyth Rd,Mailbox 511, Ottawa, ON K1H 8L6, Canada.
EM jdilworth@ohri.ca
OI Ge, Kai/0000-0002-7442-5138
FU Canadian Institutes of Health Research; Muscular Dystrophy Association;
National Institutes of Health
FX We thank LiFang Li and Esther Mak for technical assistance, and Yubing
Liu for Six4 antibody purification. This work was supported by grants
from the Canadian Institutes of Health Research (to FJD and MB), the
Muscular Dystrophy Association (to AB); and National Institutes of
Health (to KG). FJD holds a Canadian Research Chair in Epigenetic
Regulation of Transcription. MB holds a Canadian Research Chair in
Regulation of Gene Expression. SS is a fellow of the Fonds de la
Recherche en Sante Quebec.
NR 64
TC 103
Z9 108
U1 1
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD APR 21
PY 2010
VL 29
IS 8
BP 1401
EP 1411
DI 10.1038/emboj.2010.37
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 586QS
UT WOS:000276927000009
PM 20300060
ER
PT J
AU Benard, G
Neutzner, A
Peng, GH
Wang, CX
Livak, F
Youle, RJ
Karbowski, M
AF Benard, Giovanni
Neutzner, Albert
Peng, Guihong
Wang, Chunxin
Livak, Ferenc
Youle, Richard J.
Karbowski, Mariusz
TI IBRDC2, an IBR-type E3 ubiquitin ligase, is a regulatory factor for Bax
and apoptosis activation
SO EMBO JOURNAL
LA English
DT Article
DE apoptosis; Bcl-2 family; protein degradation; ubiquitin ligase
ID PROTEASOMAL DEGRADATION; MITOCHONDRIAL E3; CELL-DEATH; BCL-2; PROTEIN;
FAMILY; PERMEABILITY; MORPHOLOGY; MECHANISM; DYNAMICS
AB Bax, a pro-apoptotic protein from the Bcl-2 family, is central to apoptosis regulation. To suppress spontaneous apoptosis, Bax must be under stringent control that may include regulation of Bax conformation and expression levels. We report that IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase, regulates the levels of Bax and protects cells from unprompted Bax activation and cell death. Downregulation of IBRDC2 induces increased cellular levels and accumulation of the active form of Bax. The ubiquitination-dependent regulation of Bax stability is suppressed by IBRDC2 downregulation and stimulated by IBRDC2 overexpression in both healthy and apoptotic cells. Although mostly cytosolic in healthy cells, upon induction of apoptosis, IBRDC2 accumulates in mitochondrial domains enriched with Bax. Mitochondrial accumulation of IBRDC2 occurs in parallel with Bax activation and also depends on the expression levels of Bcl-xL. Furthermore, IBRDC2 physically interacts with activated Bax. By applying Bax mutants in HCT116 Bax(-/-) cells, combined with the use of active Bax-specific antibodies, we have established that both mitochondrial localization and apoptotic activation of Bax are required for IBRDC2 translocation to the mitochondria. The EMBO Journal (2010) 29, 1458-1471. doi: 10.1038/emboj.2010.39; Published online 18 March 2010
C1 [Benard, Giovanni; Peng, Guihong; Karbowski, Mariusz] Univ Maryland, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
[Neutzner, Albert; Wang, Chunxin; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, NIH, Bethesda, MD USA.
[Livak, Ferenc] Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA.
RP Karbowski, M (reprint author), Univ Maryland, Ctr Biomed Engn & Technol, 725 W Lombard St, Baltimore, MD 21201 USA.
EM karbowsk@umbi.umd.edu
RI Benard, Giovanni/M-3485-2014; Wang, Chunxin/B-9312-2016;
OI Wang, Chunxin/0000-0001-6015-6806; Neutzner, Albert/0000-0001-9254-5558
FU National Institute of General Medical Science [RO1 GM083131]
FX We thank Pamela Wright for comments on the paper, Xu Shan for technical
support, and James W Nagle and Debbie Kaufmann from the NINDS DNA
sequencing facility for the excellent service provided. We also
gratefully acknowledge financial support from the National Institute of
General Medical Science RO1 GM083131 (MK).
NR 50
TC 28
Z9 31
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD APR 21
PY 2010
VL 29
IS 8
BP 1458
EP 1471
DI 10.1038/emboj.2010.39
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 586QS
UT WOS:000276927000014
PM 20300062
ER
PT J
AU Laiyemo, AO
Doubeni, C
Pinsky, PF
Doria-Rose, VP
Bresalier, R
Lamerato, LE
Crawford, ED
Kvale, P
Fouad, M
Hickey, T
Riley, T
Weissfeld, J
Schoen, RE
Marcus, PM
Prorok, PC
Berg, CD
AF Laiyemo, Adeyinka O.
Doubeni, Chyke
Pinsky, Paul F.
Doria-Rose, V. Paul
Bresalier, Robert
Lamerato, Lois E.
Crawford, E. David
Kvale, Paul
Fouad, Mona
Hickey, Thomas
Riley, Thomas
Weissfeld, Joel
Schoen, Robert E.
Marcus, Pamela M.
Prorok, Philip C.
Berg, Christine D.
TI Race and Colorectal Cancer Disparities: Health-Care Utilization vs
Different Cancer Susceptibilities
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SCREENING TRIAL; FLEXIBLE SIGMOIDOSCOPY; AFRICAN-AMERICANS; ASYMPTOMATIC
ADULTS; COLON-CANCER; LUNG; PROSTATE; COLONOSCOPY; POPULATION; RISK
AB Background It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility.
Methods A total of 60 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race.
Results Among 57 561 whites and 3011 blacks who underwent FSG, 13 743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas < 10 mm), or colorectal cancer.
Conclusions We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology. J Natl Cancer Inst 2010; 102: 538-546
C1 [Laiyemo, Adeyinka O.] Howard Univ, Coll Med, Div Gastroenterol, Dept Med,Canc Ctr, Washington, DC 20060 USA.
[Laiyemo, Adeyinka O.; Doria-Rose, V. Paul; 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 01605 USA.
[Pinsky, Paul F.; Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Bresalier, Robert] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Lamerato, Lois E.] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA.
[Kvale, Paul] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA.
[Fouad, Mona] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
[Hickey, Thomas; Riley, Thomas] Informat Management Serv Inc, Rockville, MD 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,Canc Ctr, Rm 329,2041 Georgia Ave NW, Washington, DC 20060 USA.
EM adeyinka.laiyemo@howard.edu
OI Doria-Rose, Vincent/0000-0002-8802-5143; Doubeni,
Chyke/0000-0001-7495-0285
FU National Cancer Institute [N01-CN-25514, N01-CN-25522, N01-CN-25515,
N01-CN-25512, N01-CN-25513, N01-CN-25516, N01-CN-25511, N01-CN-25524,
N01-CN-25518, N01-CN-75022, N01-CN-25476, N01-CN-25404, 00002540];
University of Colorado Denver; Georgetown University; Pacific Health
Research Institute; Henry Ford Health System; University of Minnesota;
Washington University; University of Pittsburgh Medical Center;
University of Utah; Marshfield Clinic Research Foundation; University of
Alabama at Birmingham; Westat, Inc.; UCLA Immunogenetics Ctr.; NCT
FX The study was funded by the National Cancer Institute through contracts
to the participating centers associated with the PLCO trial: University
of Colorado Denver (N01-CN-25514); Georgetown University (N01-CN-25522);
Pacific Health Research Institute (N01-CN-25515); Henry Ford Health
System (N01-CN-25512); University of Minnesota (N01-CN-25513);
Washington University (N01-CN-25516); University of Pittsburgh Medical
Center (N01-CN-25511); University of Utah (N01-CN-25524); Marshfield
Clinic Research Foundation (N01-CN-25518); University of Alabama at
Birmingham (N01-CN-75022); Westat, Inc. (N01-CN-25476); UCLA
Immunogenetics Ctr. (N01-CN-25404). The clinical trials number for PLCO
trial: NCT (00002540).
NR 38
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U1 1
U2 4
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 APR 21
PY 2010
VL 102
IS 8
BP 538
EP 546
DI 10.1093/jnci/djq068
PG 9
WC Oncology
SC Oncology
GA 587NI
UT WOS:000276998800009
PM 20357245
ER
PT J
AU Kristinsson, SY
Koshiol, J
Bjorkholm, M
Goldin, LR
McMaster, ML
Turesson, I
Landgren, O
AF Kristinsson, Sigurdur Y.
Koshiol, Jill
Bjorkholm, Magnus
Goldin, Lynn R.
McMaster, Mary L.
Turesson, Ingemar
Landgren, Ola
TI Immune-Related and Inflammatory Conditions and Risk of Lymphoplasmacytic
Lymphoma or Waldenstrom Macroglobulinemia
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; MULTIPLE-MYELOMA;
UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; 1ST-DEGREE RELATIVES;
PRECURSOR DISEASES; UNITED-STATES; DISORDERS; GENE
AB Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenstrom macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immunerelated and/or inflammatory disorders and the subsequent risk of LPL-WM.
Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression.
Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjogren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjgren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain-Barre syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1).
Conclusions Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjgren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions. J Natl Cancer Inst 2010; 102: 557-567
C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
[Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
[Koshiol, Jill; Goldin, Lynn R.; McMaster, Mary L.; Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden.
RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Intramural NIH HHS
NR 31
TC 37
Z9 40
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD APR 21
PY 2010
VL 102
IS 8
BP 557
EP 567
DI 10.1093/jnci/djq043
PG 11
WC Oncology
SC Oncology
GA 587NI
UT WOS:000276998800011
PM 20181958
ER
PT J
AU Longo, DL
AF Longo, Dan L.
TI Re: Late Effects From Radiation Therapy: The Hits Just Keep on Coming
Reply
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID HODGKINS-DISEASE; CLINICAL-TRIAL; STAGE-II; RADIOTHERAPY; CHEMOTHERAPY
C1 NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Longo, DL (reprint author), NIA, Intramural Res Program, 251 Bayview Blvd,Ste 100,Rm 04C224, Baltimore, MD 21224 USA.
EM longod@grc.nia.nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD APR 21
PY 2010
VL 102
IS 8
BP 577
EP U85
DI 10.1093/jnci/djq070
PG 2
WC Oncology
SC Oncology
GA 587NI
UT WOS:000276998800018
ER
PT J
AU Schwartz, LM
Woloshin, S
Kramer, BS
AF Schwartz, Lisa M.
Woloshin, Steven
Kramer, Barnet S.
TI Re: Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor
Receptor-Targeted Therapy in Metastatic Colorectal Cancer Reply
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Schwartz, Lisa M.; Woloshin, Steven] VA Med Ctr, VA Outcomes Grp 111B, White River Jct, VT 05009 USA.
[Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dartmouth Inst Hlth Policy & Clin Practice, Dept Med, Hanover, NH USA.
[Kramer, Barnet S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Schwartz, LM (reprint author), VA Med Ctr, VA Outcomes Grp 111B, 215 N Main St, White River Jct, VT 05009 USA.
EM lisa.schwartz@dartmouth.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD APR 21
PY 2010
VL 102
IS 8
DI 10.1093/jnci/djq066
PG 2
WC Oncology
SC Oncology
GA 587NI
UT WOS:000276998800015
ER
PT J
AU Norton, KA
Wininger, M
Bhanot, G
Ganesan, S
Barnard, N
Shinbrot, T
AF Norton, Kerri-Ann
Wininger, Michael
Bhanot, Gyan
Ganesan, Shridar
Barnard, Nicola
Shinbrot, Troy
TI A 2D mechanistic model of breast ductal carcinoma in situ (DCIS)
morphology and progression
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Tumor growth parameters; Ductal morphology; Computational model; Breast
cancer
ID TUMOR-INDUCED ANGIOGENESIS; INTERSTITIAL FLUID PRESSURE;
MATHEMATICAL-MODELS; MYOEPITHELIAL CELLS; CANCER PROGRESSION;
EPITHELIAL-CELLS; SOLID TUMORS; GROWTH; CLASSIFICATION; EVOLUTION
AB Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumor in which cells proliferate abnormally, but remain confined within a duct. Although four distinguishable DCIS morphologies are recognized, the mechanisms that generate these different morphological classes remain unclear, and consequently the prognostic strength of DCIS classification is not strong. To improve the understanding of the relation between morphology and time course, we have developed a 2D in silico particle model of the growth of DCIS within a single breast duct. This model considers mechanical effects such as cellular adhesion and intra-ductal pressure, and biological features including proliferation, apoptosis, necrosis, and cell polarity. Using this model, we find that different regions of parameter space generate distinct morphological subtypes of DCIS, so elucidating the relation between morphology and time course. Furthermore, we find that tumors with similar architectures may in fact be produced through different mechanisms, and we propose future work to further disentangle the mechanisms involved in DCIS progression. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Norton, Kerri-Ann; Bhanot, Gyan] Rutgers State Univ, BioMaPS Inst, Piscataway, NJ 08854 USA.
[Wininger, Michael] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20817 USA.
[Bhanot, Gyan] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
[Bhanot, Gyan] Rutgers State Univ, Dept Phys, Piscataway, NJ 08854 USA.
[Bhanot, Gyan] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA.
[Bhanot, Gyan; Ganesan, Shridar] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Barnard, Nicola] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pathol, New Brunswick, NJ 08903 USA.
RP Norton, KA (reprint author), Rutgers State Univ, BioMaPS Inst, Piscataway, NJ 08854 USA.
EM kerrin@eden.rutgers.edu; wininger@eden.rutgers.edu;
gyanbhanot@rci.rutgers.edu; ganesash@umdnj.edu; barnarni@umdnj.edu;
shinbrot@soemail.rutgers.edu
FU New Jersey Commission on Cancer Research; NIH [1 S10 RR022375]
FX We thank R. Toth, Dr. D. Silver, Dr. A. Madabhushi, and Dr. D. Foran for
their help with the imaging part of this project. We also thank Dr. D.
Axelrod for his valuable discussions on breast cancer. This project was
funded in part by the New Jersey Commission on Cancer Research, and data
were collected using the Gyges cluster from the BioMaPs institute,
funded by the NIH Grant# 1 S10 RR022375.
NR 81
TC 16
Z9 16
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
J9 J THEOR BIOL
JI J. Theor. Biol.
PD APR 21
PY 2010
VL 263
IS 4
BP 393
EP 406
DI 10.1016/j.jtbi.2009.11.024
PG 14
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 572MV
UT WOS:000275837800001
PM 20006623
ER
PT J
AU Baber, I
Keita, M
Sogoba, N
Konate, M
Diallo, M
Doumbia, S
Traore, SF
Ribeiro, JMC
Manoukis, NC
AF Baber, Ibrahima
Keita, Moussa
Sogoba, Nafomon
Konate, Mamadou
Diallo, M'Bouye
Doumbia, Seydou
Traore, Sekou F.
Ribeiro, Jose M. C.
Manoukis, Nicholas C.
TI Population Size and Migration of Anopheles gambiae in the Bancoumana
Region of Mali and Their Significance for Efficient Vector Control
SO PLOS ONE
LA English
DT Article
ID MALARIA TRANSMISSION; DRY SEASON; COMPLEX MOSQUITOS; CHROMOSOMAL FORMS;
SUDAN SAVANNA; DISPERSAL; VILLAGE; IDENTIFICATION; INTERVENTIONS;
SURVIVAL
AB We present results of two intensive mark-release-recapture surveys conducted during the wet and dry seasons of 2008 in the villages of Fourda and Kenieroba, Mali. The former is a small fishing village by the Niger River with a moderate to high densities of Anopheles gambiae Giles s.s. (Diptera: Culicidae) throughout the year, while the latter is a large agricultural community 2 km inland that experiences strong seasonal fluctuation in An. gambiae densities. We estimate the population size of female An. gambiae in Fourda to be in less than 3,000 during the dry season. We found evidence of large population size and migration from Fourda in Kenieroba during the wet season, but very low numbers and no sign of migrants during the dry season. We suggest that malaria vector control measures aimed at adult mosquitoes might be made more efficient in this region and other seasonal riparian habitats by targeting disruption of mosquito populations by the river during the dry season. This would decrease the size of an already small population, and would be likely to delay the explosive growth in vector numbers in the larger inland villages as rainfall increases.
C1 [Baber, Ibrahima; Keita, Moussa; Sogoba, Nafomon; Konate, Mamadou; Diallo, M'Bouye; Doumbia, Seydou; Traore, Sekou F.] Univ Mali, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
[Ribeiro, Jose M. C.; Manoukis, Nicholas C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Baber, I (reprint author), Univ Mali, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
EM manoukisn@niaid.nih.gov
OI Ribeiro, Jose/0000-0002-9107-0818
FU National Institutes of Allergies and Infectious Diseases (NIAID);
National Institutes of Health
FX This study was supported by the intramural program of the National
Institutes of Allergies and Infectious Diseases (NIAID), National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 12
Z9 12
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 21
PY 2010
VL 5
IS 4
AR e10270
DI 10.1371/journal.pone.0010270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586YS
UT WOS:000276952500025
PM 20422013
ER
PT J
AU Ciribilli, Y
Andreotti, V
Menendez, D
Langen, JS
Schoenfelder, G
Resnick, MA
Inga, A
AF Ciribilli, Yari
Andreotti, Virginia
Menendez, Daniel
Langen, Jan-Stephan
Schoenfelder, Gilbert
Resnick, Michael A.
Inga, Alberto
TI The Coordinated P53 and Estrogen Receptor Cis-Regulation at an FLT1
Promoter SNP Is Specific to Genotoxic Stress and Estrogenic Compound
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR P53; FACTOR-BINDING-SITES;
RESPONSE ELEMENTS; TRANSCRIPTION-FACTOR; BREAST-CANCER; DNA-DAMAGE;
GENE-EXPRESSION; VEGF; CELLS
AB Background: Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a 1/2 site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an estrogen receptor (ER) 1/2 site response element (ERE1) 225 nt upstream to the RE-T.
Methodology/Principal Findings: Here we report the identification of a second ER K site (ERE2) located 145 bp downstream of the RE-T and establish that both EREs can impact p53-mediated transactivation of FLT1-T in a manner that is cell type and ER level dependent. Gene reporter assays and ChIP experiments conducted in the breast cancer-derived MCF7 cells revealed that the ERE2 site was sufficient for p53-mediated ER alpha recruitment and transactivation of the FLT1-T promoter/reporter construct. Surprisingly, unlike the case for other p53 target promoters, p53-mediated transactivation of FLT1-T constructs or expression of the endogenous FLT1 gene, as well as binding of p53 and ER at the promoter constructs, was inducible by doxorubicin but not by 5-fluorouracil. Furthermore, ER activity at FLT1-T was differentially affected by ER ligands, compared to a control TFF1/pS2 ER target promoter. The p53-related transcription factors (TFs) p73 and p63 had no effect on FLT1 transactivation.
Conclusions/Significance: We establish a new dimension to the p53 master regulatory network where p53-mediated transcription from a 1/2 site RE can be determined by ER binding at one or more cis-acting EREs in manner that is dependent on level of ER protein, the type of ER ligand and the specific p53-inducing agent.
C1 [Ciribilli, Yari; Andreotti, Virginia; Inga, Alberto] Natl Inst Canc Res, IST, Unit Mol Mutagenesis & DNA Repair, Genoa, Italy.
[Menendez, Daniel; Resnick, Michael A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Langen, Jan-Stephan; Schoenfelder, Gilbert] Charite, Inst Clin Pharmacol & Toxicol, D-13353 Berlin, Germany.
[Schoenfelder, Gilbert] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany.
[Inga, Alberto] Univ Trent, CIBIO, Ctr Integrat Biol, Trento, Italy.
RP Ciribilli, Y (reprint author), Natl Inst Canc Res, IST, Unit Mol Mutagenesis & DNA Repair, Genoa, Italy.
EM inga@science.unitn.it
RI Andreotti, Virginia/K-4506-2016;
OI Andreotti, Virginia/0000-0002-2569-0832; Schonfelder,
Gilbert/0000-0001-6134-1990
FU Italian Association for Cancer Research, AIRC; NIEHS [1 Z01 ES065079];
Charite-Universitaetsmedizin Berlin; PhD School of Genetics Oncology and
Developmental Biology, University of Genoa, Italy
FX This work was partially supported by the Italian Association for Cancer
Research, AIRC (to AI), intramural research funds from NIEHS project 1
Z01 ES065079 (to DM and MAR) and by the Charite-Universitaetsmedizin
Berlin (to GS). YC was supported by a fellowship from the PhD School of
Genetics Oncology and Developmental Biology, University of Genoa, Italy.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 68
TC 18
Z9 19
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 21
PY 2010
VL 5
IS 4
AR e10236
DI 10.1371/journal.pone.0010236
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586YS
UT WOS:000276952500012
PM 20422012
ER
PT J
AU Croswell, JM
Baker, SG
Marcus, PM
Clapp, JD
Kramer, BS
AF Croswell, Jennifer M.
Baker, Stuart G.
Marcus, Pamela M.
Clapp, Jonathan D.
Kramer, Barnett S.
TI Cumulative Incidence of False-Positive Test Results in Lung Cancer
Screening A Randomized Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID SPIRAL COMPUTED-TOMOGRAPHY; FOLLOW-UP; INTRAOBSERVER VARIABILITY;
PULMONARY NODULES; CHEST RADIOGRAPH; BREAST-CANCER; CT-SCAN; RADIATION;
RISK; INTEROBSERVER
AB Background: Direct-to-consumer promotion of lung cancer screening has increased, especially low-dose computed tomography (CT). However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported.
Objective: To quantify the cumulative risk that a person who participated in a 1- or 2-year lung cancer screening examination would receive at least 1 false-positive result, as well as rates of unnecessary diagnostic procedures.
Design: Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.govregistration number: NCT00006382) Setting: Feasibility study for the ongoing National Lung Screening Trial.
Patients: Current or former smokers, aged 55 to 74 years, with a smoking history of 30 pack-years or more and no history of lung cancer (n = 3190).
Intervention: Random assignment to low-dose CT or chest radiography with baseline and 1 repeated annual screening; 1-year follow-up after the final screening. Randomization was centralized and stratified by age, sex, and study center.
Measurements: False-positive screenings, defined as a positive screening with a completed negative work-up or 12 months or more of follow-up with no lung cancer diagnosis.
Results: By using a Kaplan-Meier analysis, a person's cumulative probability of 1 or more false-positive low-dose CT examinations was 21% (95% CI, 19% to 23%) after 1 screening and 33% ( CI, 31% to 35%) after 2. The rates for chest radiography were 9% ( CI, 8% to 11%) and 15% ( CI, 13% to 16%), respectively. A total of 7% of participants with a false-positive low-dose CT examination and 4% with a false-positive chest radiography had a resulting invasive procedure.
Limitations: Screening was limited to 2 rounds. Follow-up after the second screening was limited to 12 months. The false-negative rate is probably an underestimate.
Conclusion: Risks for false-positive results on lung cancer screening tests are substantial after only 2 annual examinations, particularly for low-dose CT. Further study of resulting economic, psychosocial, and physical burdens of these methods is warranted.
C1 [Croswell, Jennifer M.] NCI, Off Med Applicat Res, NIH, Bethesda, MD 20892 USA.
Informat Management Serv Inc, Rockville, MD USA.
RP Croswell, JM (reprint author), NCI, Off Med Applicat Res, NIH, 6100 Execut Blvd,Suite 2B-03, Bethesda, MD 20892 USA.
EM croswellj@od.nih.gov
FU National Cancer Institute
FX Primary Funding Source: National Cancer Institute.
NR 45
TC 58
Z9 62
U1 1
U2 11
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 20
PY 2010
VL 152
IS 8
BP 505
EP U53
DI 10.7326/0003-4819-152-8-201004200-00007
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 588FV
UT WOS:000277054400004
PM 20404381
ER
PT J
AU Gail, MH
Schairer, C
AF Gail, Mitchell H.
Schairer, Catherine
TI Comments and Response on the USPSTF Recommendation on Screening for
Breast Cancer
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Gail, Mitchell H.; Schairer, Catherine] NCI, Bethesda, MD 20892 USA.
RP Gail, MH (reprint author), NCI, Bethesda, MD 20892 USA.
NR 4
TC 3
Z9 3
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 20
PY 2010
VL 152
IS 8
BP 540
EP 540
DI 10.7326/0003-4819-152-8-201004200-00202
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 588FV
UT WOS:000277054400016
PM 20157102
ER
PT J
AU Little, MP
AF Little, Mark P.
TI Cancer models, genomic instability and somatic cellular Darwinian
evolution
SO BIOLOGY DIRECT
LA English
DT Review
ID CLONAL EXPANSION MODEL; NONPOLYPOSIS COLON-CANCER; LUNG-TUMOR RISK;
GENETIC INSTABILITY; MICROSATELLITE-INSTABILITY; COLORECTAL-CANCER;
2-MUTATION MODEL; MULTISTAGE CARCINOGENESIS; AGE DISTRIBUTION; 2-STAGE
MODEL
AB The biology of cancer is critically reviewed and evidence adduced that its development can be modelled as a somatic cellular Darwinian evolutionary process. The evidence for involvement of genomic instability (GI) is also reviewed. A variety of quasi-mechanistic models of carcinogenesis are reviewed, all based on this somatic Darwinian evolutionary hypothesis; in particular, the multi-stage model of Armitage and Doll (Br. J. Cancer 1954: 8; 1-12), the two-mutation model of Moolgavkar, Venzon, and Knudson (MVK) (Math. Biosci. 1979: 47; 55-77), the generalized MVK model of Little (Biometrics 1995: 51; 1278-1291) and various generalizations of these incorporating effects of GI (Little and Wright Math. Biosci. 2003: 183; 111-134; Little et al. J. Theoret. Biol. 2008: 254; 229-238).
C1 [Little, Mark P.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England.
RP Little, MP (reprint author), NCI, Epidemiol Branch, Execut Plaza S,6120 Execut Blvd MSC 7238, Bethesda, MD 20892 USA.
EM mark.little@imperial.ac.uk
OI Little, Mark/0000-0003-0980-7567
FU European Commission [FP6-036465]
FX This work has been partially funded by the European Commission under
contract FP6-036465 (NOTE). The author is grateful for the detailed and
helpful comments of Dr Guangquan Li, Professor Paolo Vineis, three
referees and the editor.
NR 166
TC 21
Z9 23
U1 2
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD APR 20
PY 2010
VL 5
AR 19
DI 10.1186/1745-6150-5-19
PG 19
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 597UA
UT WOS:000277786200001
PM 20406436
ER
PT J
AU Ning, YM
Gulley, JL
Arlen, PM
Woo, S
Steinberg, SM
Wright, JJ
Parnes, HL
Trepel, JB
Lee, MJ
Kim, YS
Sun, H
Madan, RA
Latham, L
Jones, E
Chen, CC
Figg, WD
Dahut, WL
AF Ning, Yang-Min
Gulley, James L.
Arlen, Philip M.
Woo, Sukyung
Steinberg, Seth M.
Wright, John J.
Parnes, Howard L.
Trepel, Jane B.
Lee, Min-Jung
Kim, Yeong Sang
Sun, Haihao
Madan, Ravi A.
Latham, Lea
Jones, Elizabeth
Chen, Clara C.
Figg, William D.
Dahut, William L.
TI Phase II Trial of Bevacizumab, Thalidomide, Docetaxel, and Prednisone in
Patients With Metastatic Castration-Resistant Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MITOXANTRONE PLUS PREDNISONE;
CLINICAL-TRIALS; SOLID TUMORS; THERAPY; COMBINATION; MODEL;
PHARMACOKINETICS; OSTEONECROSIS; ANGIOGENESIS
AB Purpose
We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity. To explore safety and efficacy, this was tested in mice and in human patients.
Patients and Methods
Preclinical efficacy of the combination therapy was evaluated in PC3 xenograft mice. Sixty patients with progressive metastatic CRPC received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone. The primary end point was a prostate-specific antigen (PSA) decline of >= 50%. Secondary end points included time to progression, overall survival, and safety.
Results
In the mouse model, combination therapy of docetaxel, bevacizumab, and thalidomide inhibited tumor growth most effectively. In the clinical trial, 90% of patients receiving the combination therapy had PSA declines of >= 50%, and 88% achieved a PSA decline of >= 30% within the first 3 months of treatment. The median time to progression was 18.3 months, and the median overall survival was 28.2 months in this group with a Halabi-predicted survival of 14 months. While toxicities were manageable, all patients developed grade 3/4 neutropenia.
Conclusion
The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities. The estimated median survival is encouraging, given the generally poor prognosis of this patient population. These results suggest that definitive clinical trials combining antiangiogenic agent combinations with docetaxel are warranted to improve treatment outcomes for patients with metastatic CRPC. J Clin Oncol 28: 2070-2076. Published by the American Society of Clinical Oncology
C1 NCI, Tumor Immunol & Biol Lab, Clin Pharmacol Res Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
NCI, Dept Radiol & Imaging Sci, Ctr Clin, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), Bldg 10,Rm 5A01,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health.
NR 31
TC 89
Z9 93
U1 3
U2 7
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 APR 20
PY 2010
VL 28
IS 12
BP 2070
EP 2076
DI 10.1200/JCO.2009.25.4524
PG 7
WC Oncology
SC Oncology
GA 584PF
UT WOS:000276764000018
PM 20308663
ER
PT J
AU Korde, LA
Zujewski, JA
Kamin, L
Giordano, S
Domchek, S
Anderson, WF
Bartlett, JMS
Gelmon, K
Nahleh, Z
Bergh, J
Cutuli, B
Pruneri, G
McCaskill-Stevens, W
Gralow, J
Hortobagyi, G
Cardoso, F
AF Korde, Larissa A.
Zujewski, Jo Anne
Kamin, Leah
Giordano, Sharon
Domchek, Susan
Anderson, William F.
Bartlett, John M. S.
Gelmon, Karen
Nahleh, Zeina
Bergh, Jonas
Cutuli, Bruno
Pruneri, Giancarlo
McCaskill-Stevens, Worta
Gralow, Julie
Hortobagyi, Gabriel
Cardoso, Fatima
TI Multidisciplinary Meeting on Male Breast Cancer: Summary and Research
Recommendations
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BRCA1 MUTATION CARRIERS; LYMPH-NODE BIOPSY; KLINEFELTERS-SYNDROME;
GERMLINE MUTATIONS; RISK-FACTORS; CARCINOMA; MEN; SURVIVAL;
SUSCEPTIBILITY; CHEK2-ASTERISK-1100DELC
AB Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Most data on male breast cancer comes from small single-institution studies, and because of the paucity of data, the optimal treatment for male breast cancer is not known. This article summarizes a multidisciplinary international meeting on male breast cancer, sponsored by the National Institutes of Health Office of Rare Diseases and the National Cancer Institute Divisions of Cancer Epidemiology and Genetics and Cancer Treatment and Diagnosis. The meeting included representatives from the fields of epidemiology, genetics, pathology and molecular biology, health services research, and clinical oncology and the advocacy community, with a comprehensive review of the data. Presentations focused on highlighting differences and similarities between breast cancer in males and females. To enhance our understanding of male breast cancer, international consortia are necessary. Therefore, the Breast International Group and North American Breast Cancer Group have joined efforts to develop an International Male Breast Cancer Program and to pool epidemiologic data, clinical information, and tumor specimens. This international collaboration will also facilitate the future planning of clinical trials that can address essential questions in the treatment of male breast cancer. J Clin Oncol 28: 2114- 2122. (C) 2010 by American Society of Clinical Oncology
C1 [Korde, Larissa A.] Univ Washington, Div Med Oncol, Seattle, WA 98109 USA.
Seattle Canc Care Alliance, Seattle, WA USA.
NCI, Clin Invest Branch, Div Canc Diag & Treatment, Bethesda, MD 20892 USA.
NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
Emmes Corp, Rockville, MD USA.
Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Univ Edinburgh, Dept Pathol, Edinburgh Canc Res Ctr, Endocrine Canc Grp, Edinburgh, Midlothian, Scotland.
British Columbia Canc Agcy, Natl Canc Inst, Canada Clin Trials Grp, Vancouver, BC V5Z 4E6, Canada.
Karolinska Inst, Stockholm, Sweden.
Univ Hosp, Breast Sarcoma Sect, Stockholm, Sweden.
Clin Trial Unit, Stockholm, Sweden.
Polyclin Courlancy, Reims, France.
European Inst Oncol, Milan, Italy.
Inst Jules Bordet, B-1000 Brussels, Belgium.
Breast Int Grp, Brussels, Belgium.
RP Korde, LA (reprint author), Univ Washington, Div Med Oncol, 825 Eastlake Ave E,MS G3-630, Seattle, WA 98109 USA.
EM lkorde@u.washington.edu
OI Cardoso, Fatima/0000-0002-6692-2249
FU National Institutes of Health (NIH); National Cancer Institute (NCI)
FX Supported by the Intramural Research Program of the National Institutes
of Health (NIH) and National Cancer Institute (NCI). Funding for the NCI
Multidisciplinary Male Breast Cancer Scientific Meeting was provided by
the Office of Rare Diseases, NIH, and by the Division of Cancer
Epidemiology and Genetics and Division of Cancer Treatment and
Diagnosis, NCI.
NR 64
TC 117
Z9 127
U1 0
U2 10
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 APR 20
PY 2010
VL 28
IS 12
BP 2114
EP 2122
DI 10.1200/JCO.2009.25.5729
PG 9
WC Oncology
SC Oncology
GA 584PF
UT WOS:000276764000024
PM 20308661
ER
PT J
AU Lam, CSP
AF Lam, Carolyn S. P.
TI Heart Failure With Preserved Ejection Fraction Invasive Solution to
Diagnostic Confusion?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE heart failure; preserved ejection fraction; diastolic dysfunction;
catheterization
ID EXTERNAL FORCES; STIFFNESS; RELAXATION
C1 [Lam, Carolyn S. P.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Lam, Carolyn S. P.] Mayo Clin, Rochester, MN USA.
[Lam, Carolyn S. P.] Natl Univ Hlth Syst, Singapore, Singapore.
RP Lam, CSP (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM lam.suping@mayo.edu
NR 14
TC 12
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 20
PY 2010
VL 55
IS 16
BP 1710
EP 1711
DI 10.1016/j.jacc.2009.12.034
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 583AX
UT WOS:000276644700009
PM 20394875
ER
PT J
AU Weisfeldt, ML
Sitlani, CM
Ornato, JP
Rea, T
Aufderheide, TP
Davis, D
Dreyer, J
Hess, EP
Jui, J
Maloney, J
Sopko, G
Powell, J
Nichol, G
Morrison, LJ
AF Weisfeldt, Myron L.
Sitlani, Colleen M.
Ornato, Joseph P.
Rea, Thomas
Aufderheide, Tom P.
Davis, Daniel
Dreyer, Jonathan
Hess, Erik P.
Jui, Jonathan
Maloney, Justin
Sopko, George
Powell, Judy
Nichol, Graham
Morrison, Laurie J.
CA ROC Investigators
TI Survival After Application of Automatic External Defibrillators Before
Arrival of the Emergency Medical System Evaluation in the Resuscitation
Outcomes Consortium Population of 21 Million
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE automatic external defibrillator; cardiac arrest; cardiopulmonary
resuscitation; defibrillation; resuscitation
ID HOSPITAL CARDIAC-ARREST; PUBLIC-ACCESS DEFIBRILLATION; QUALITY-OF-LIFE;
CARDIOPULMONARY-RESUSCITATION; COST-EFFECTIVENESS; TRIAL METHODS;
RATIONALE; POLICE; IMPACT; METHODOLOGY
AB Objectives The purpose of this study was to assess the effectiveness of contemporary automatic external defibrillator (AED) use.
Background In the PAD (Public Access Defibrillation) trial, survival was doubled by focused training of lay volunteers to use an AED in high-risk public settings.
Methods We performed a population-based cohort study of persons with nontraumatic out-of-hospital cardiac arrest before emergency medical system (EMS) arrival at Resuscitation Outcomes Consortium (ROC) sites between December 2005 and May 2007. Multiple logistic regression was used to assess the independent association between AED application and survival to hospital discharge.
Results Of 13,769 out-of-hospital cardiac arrests, 4,403 (32.0%) received bystander cardiopulmonary resuscitation but had no AED applied before EMS arrival, and 289 (2.1%) had an AED applied before EMS arrival. The AED was applied by health care workers (32%), lay volunteers (35%), police (26%), or unknown (7%). Overall survival to hospital discharge was 7%. Survival was 9% (382 of 4,403) with bystander cardiopulmonary resuscitation but no AED, 24% (69 of 289) with AED application, and 38% (64 of 170) with AED shock delivered. In multivariable analyses adjusting for: 1) age and sex; 2) bystander cardiopulmonary resuscitation performed; 3) location of arrest (public or private); 4) EMS response interval; 5) arrest witnessed; 6) initial shockable or not shockable rhythm; and 7) study site, AED application was associated with greater likelihood of survival (odds ratio: 1.75; 95% confidence interval: 1.23 to 2.50; p < 0.002). Extrapolating this greater survival from the ROC EMS population base (21 million) to the population of the U. S. and Canada (330 million), AED application by bystanders seems to save 474 lives/year.
Conclusions Application of an AED in communities is associated with nearly a doubling of survival after out-of-hospital cardiac arrest. These results reinforce the importance of strategically expanding community-based AED programs. (J Am Coll Cardiol 2010;55:1713-20) (C) 2010 by the American College of Cardiology Foundation
C1 [Weisfeldt, Myron L.] Johns Hopkins Univ, Baltimore, MD 21287 USA.
[Sitlani, Colleen M.; Rea, Thomas; Powell, Judy; Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Ornato, Joseph P.] Virginia Commonwealth Univ, Richmond, VA USA.
[Aufderheide, Tom P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Davis, Daniel] Univ Calif San Diego, San Diego, CA 92103 USA.
[Dreyer, Jonathan] Univ Western Ontario, London, ON, Canada.
[Hess, Erik P.] Mayo Clin, Rochester, MN USA.
[Jui, Jonathan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Maloney, Justin] Univ Ottawa, Ottawa, ON, Canada.
[Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA.
[Morrison, Laurie J.] Univ Toronto, Toronto, ON, Canada.
RP Weisfeldt, ML (reprint author), Johns Hopkins Univ, 1830 E Monument St,Suite 9026, Baltimore, MD 21287 USA.
EM mlw5@jhmi.edu
RI morrison, laurie/A-6325-2012
OI morrison, laurie/0000-0001-8369-9774
FU National Heart, Lung and Blood Institute in partnership with the
National Institute of Neurological Disorders and Stroke [5U01 HL077863,
HL077881, HL077871, HL077872, HL077866, HL077908, HL077867, HL077885,
HL077887, HL077873, HL077865]; U.S. Army Medical Research & Material
Command; Canadian Institutes of Health Research (CIHR)-Institute of
Circulatory and Respiratory Health; Defence Research and Development
Canada; American Heart Association; Heart and Stroke Foundation of
Canada; Medtronic, Inc.; Innercool Therapies Inc.; Radiant Medical Inc.
FX The Resuscitation Outcomes Consortium (ROC) is supported by a series of
cooperative agreements to 10 regional clinical centers and 1 data
coordinating center (5U01 HL077863, HL077881, HL077871 HL077872,
HL077866, HL077908, HL077867, HL077885, HL077887, HL077873, and
HL077865) from the National Heart, Lung and Blood Institute in
partnership with the National Institute of Neurological Disorders and
Stroke; the U.S. Army Medical Research & Material Command; The Canadian
Institutes of Health Research (CIHR)-Institute of Circulatory and
Respiratory Health; Defence Research and Development Canada; the
American Heart Association; and the Heart and Stroke Foundation of
Canada. Some ROC site emergency medical systems have received equipment
or concessions from automatic external defibrillator manufacturers. The
ROC coordinating center accepts support for receptions from
corporations. Dr. Weisfeldt receives salary support from NIH via the
ROC. Dr. Ornato is an unpaid Science Advisory Board member of Zoll. Dr.
Rea received research support from Medtronic, Inc., and Philips, Inc.
Dr. Aufderheide is a consultant for Medtronics, Inc., and JoLife, Inc.
Dr. Nichol is a co-principal investigator of the ROC Data Coordinating
Center (NHLBI); principal investigator of the randomized trial of
hemofiltration after resuscitation from cardiac arrest (NHLBI);
co-investigator of the randomized field trial of cold saline IV after
resuscitation after cardiac arrest (NHLBI); principal investigator of
the randomized trial of CPR training aid in community (Asmund S. Laerdal
Foundation for Acute Medicine); has received travel expenses from
Innercool Therapies Inc., Radiant Medical Inc., and the American Heart
Association; and is a consultant for Triage Wireless.
NR 42
TC 181
Z9 186
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 20
PY 2010
VL 55
IS 16
BP 1712
EP 1719
DI 10.1016/j.jacc.2009.11.077
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 583AX
UT WOS:000276644700010
PM 20394876
ER
PT J
AU Ascierto, PA
Streicher, HZ
Sznol, M
AF Ascierto, Paolo A.
Streicher, Howard Z.
Sznol, Mario
TI Melanoma: A model for testing new agents in combination therapies
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID METASTATIC MALIGNANT-MELANOMA; RANDOMIZED PHASE-III; OVERCOMING
IMMUNOLOGICAL-TOLERANCE; HISTONE DEACETYLASE INHIBITORS;
COOPERATIVE-ONCOLOGY-GROUP; STAGE-IV MELANOMA; CELL LUNG-CANCER;
SUBCUTANEOUS INTERLEUKIN-2; EUROPEAN ORGANIZATION; MYELOID-LEUKEMIA
AB Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time.
C1 [Ascierto, Paolo A.] Natl Tumor Inst, Unit Med Oncol & Innovat Therapy, Naples, Italy.
[Streicher, Howard Z.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Sznol, Mario] Yale Univ, Sch Med, Melanoma Program, New Haven, CT USA.
RP Ascierto, PA (reprint author), Natl Tumor Inst, Unit Med Oncol & Innovat Therapy, Naples, Italy.
EM paolo.ascierto@gmail.com
NR 82
TC 31
Z9 32
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD APR 20
PY 2010
VL 8
AR 38
DI 10.1186/1479-5876-8-38
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 604RC
UT WOS:000278295200001
PM 20406483
ER
PT J
AU Fiocco, AJ
Lindquist, K
Ferrell, R
Li, R
Simonsick, EM
Nalls, M
Harris, TB
Yaffe, K
AF Fiocco, A. J.
Lindquist, K.
Ferrell, R.
Li, R.
Simonsick, E. M.
Nalls, M.
Harris, T. B.
Yaffe, K.
CA Hlth ABC Study
TI COMT genotype and cognitive function An 8-year longitudinal study in
white and black elders
SO NEUROLOGY
LA English
DT Article
ID CATECHOL-O-METHYLTRANSFERASE; OLDER-ADULTS; PREFRONTAL FUNCTION;
ALZHEIMER-DISEASE; BODY-COMPOSITION; MESSENGER-RNA; POLYMORPHISM;
DOPAMINE; DEMENTIA; BRAIN
AB Objective: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val(158)met) genotype and cognition in older adults.
Methods: We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined.
Results: Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]).
Conclusion: These findings suggest that the Val allele has a protective impact on cognitive decline in late life. Neurology (R) 2010;74:1296-1302
C1 [Fiocco, A. J.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94121 USA.
[Lindquist, K.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94121 USA.
[Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Ferrell, R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Li, R.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Nalls, M.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Fiocco, AJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Psychiat, 4150 Clement St,Box 116H, San Francisco, CA 94121 USA.
EM afiocco@klaru-baycrest.on.ca
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Kritchevsky,
Stephen/0000-0003-3336-6781
FU NIH, National Institute on Aging; Canadian Institute of Health;
[N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106];
[1R21DK068608-01A2]; [AG031155]
FX Funded by N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The
measurement of F2-isoprostane was funded by 1R21DK068608-01A2. This
research was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging. Dr. Fiocco is supported by the
Canadian Institute of Health Research Fellowship in the area of
Longitudinal Study on Aging. Dr. Yaffe was supported in part by AG031155
and an anonymous foundation.
NR 40
TC 13
Z9 13
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 20
PY 2010
VL 74
IS 16
BP 1296
EP 1302
DI 10.1212/WNL.0b013e3181d9edba
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 585HQ
UT WOS:000276816200010
PM 20404311
ER
PT J
AU Matveeva, OV
Kang, YB
Spiridonov, AN
Saetrom, P
Nemtsov, VA
Ogurtsov, AY
Nechipurenko, YD
Shabalina, SA
AF Matveeva, Olga V.
Kang, Yibin
Spiridonov, Alexey N.
Saetrom, Pal
Nemtsov, Vladimir A.
Ogurtsov, Aleksey Y.
Nechipurenko, Yury D.
Shabalina, Svetlana A.
TI Optimization of Duplex Stability and Terminal Asymmetry for shRNA Design
SO PLOS ONE
LA English
DT Article
ID RNA SECONDARY STRUCTURE; SIRNA DESIGN; MAMMALIAN-CELLS; FUNCTIONAL
SIRNAS; EFFICIENCY; INTERFERENCE; SPECIFICITY; EXPRESSION; PARAMETERS;
KNOCKDOWN
AB Prediction of efficient oligonucleotides for RNA interference presents a serious challenge, especially for the development of genome-wide RNAi libraries which encounter difficulties and limitations due to ambiguities in the results and the requirement for significant computational resources. Here we present a fast and practical algorithm for shRNA design based on the thermodynamic parameters. In order to identify shRNA and siRNA features universally associated with high silencing efficiency, we analyzed structure-activity relationships in thousands of individual RNAi experiments from publicly available databases (ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/). Using this statistical analysis, we found free energy ranges for the terminal duplex asymmetry and for fully paired duplex stability, such that shRNAs or siRNAs falling in both ranges have a high probability of being efficient. When combined, these two parameters yield a similar to 72% success rate on shRNAs from the siRecords database, with the target RNA levels reduced to below 20% of the control. Two other parameters correlate well with silencing efficiency: the stability of target RNA and the antisense strand secondary structure. Both parameters also correlate with the short RNA duplex stability; as a consequence, adding these parameters to our prediction scheme did not substantially improve classification accuracy. To test the validity of our predictions, we designed 83 shRNAs with optimal terminal asymmetry, and experimentally verified that small shifts in duplex stability strongly affected silencing efficiency. We showed that shRNAs with short fully paired stems could be successfully selected by optimizing only two parameters: terminal duplex asymmetry and duplex stability of the hypothetical cleavage product, which also relates to the specificity of mRNA target recognition. Our approach performs at the level of the best currently utilized algorithms that take into account prediction of the secondary structure of the target and antisense RNAs, but at significantly lower computational costs. Based on this study, we created the si-shRNA Selector program that predicts both highly efficient shRNAs and functional siRNAs ( ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/).
C1 [Matveeva, Olga V.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Kang, Yibin] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Spiridonov, Alexey N.] MIT, Dept Appl Math, Cambridge, MA 02139 USA.
[Saetrom, Pal] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, N-7034 Trondheim, Norway.
[Saetrom, Pal] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7034 Trondheim, Norway.
[Nemtsov, Vladimir A.] Russian Acad Sci, MGGT, Moscow, Russia.
[Nechipurenko, Yury D.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia.
[Ogurtsov, Aleksey Y.; Shabalina, Svetlana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Matveeva, OV (reprint author), Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
EM olga.matveeva@gmail.com; shabalin@ncbi.nlm.nih.gov
RI Shabalina, Svetlana/N-8939-2013;
OI Shabalina, Svetlana/0000-0003-2272-7473; Saetrom,
Pal/0000-0001-8142-7441
FU Department of Health and Human Services (National Institutes of Health,
National Library of Medicine); Russian Foundation for Basic Research and
the RAS Presidium "Molecular and cell biology''
FX The research was supported by the Department of Health and Human
Services (National Institutes of Health, National Library of Medicine)
intramural funds. YDN was supported by the Russian Foundation for Basic
Research and the RAS Presidium "Molecular and cell biology''. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 38
TC 18
Z9 19
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 20
PY 2010
VL 5
IS 4
AR e10180
DI 10.1371/journal.pone.0010180
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 585UH
UT WOS:000276854300001
PM 20422034
ER
PT J
AU Cho, HS
Dashdorj, N
Schotte, F
Graber, T
Henning, R
Anfinrud, P
AF Cho, Hyun Sun
Dashdorj, Naranbaatar
Schotte, Friedrich
Graber, Timothy
Henning, Robert
Anfinrud, Philip
TI Protein structural dynamics in solution unveiled via 100-ps
time-resolved x-ray scattering
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CARBON-MONOXIDE; MYOGLOBIN; HEMOGLOBIN; CRYSTALLOGRAPHY; SPECTROSCOPY;
PHOTODISSOCIATION; RELAXATION; ASSEMBLIES; COMPLEXES; COLLAPSE
AB We have developed a time-resolved x-ray scattering diffractometer capable of probing structural dynamics of proteins in solution with 100-ps time resolution. This diffractometer, developed on the ID14B BioCARS (Consortium for Advanced Radiation Sources) beamline at the Advanced Photon Source, records x-ray scattering snapshots over a broad range of q spanning 0.02-2.5 angstrom(-1), thereby providing simultaneous coverage of the small-angle x-ray scattering (SAXS) and wide-angle x-ray scattering (WAXS) regions. To demonstrate its capabilities, we have tracked structural changes in myoglobin as it undergoes a photolysis-induced transition from its carbon monoxy form (MbCO) to its deoxy form (Mb). Though the differences between the MbCO and Mb crystal structures are small (rmsd <0.2 angstrom), time-resolved x-ray scattering differences recorded over 8 decades of time from 100 ps to 10 ms are rich in structure, illustrating the sensitivity of this technique. A strong, negative-going feature in the SAXS region appears promptly and corresponds to a sudden >22 angstrom(3) volume expansion of the protein. The ensuing conformational relaxation causes the protein to contract to a volume similar to 2 angstrom(3) larger than MbCO within similar to 10 ns. On the timescale for CO escape from the primary docking site, another change in the SAXS/WAXS fingerprint appears, demonstrating sensitivity to the location of the dissociated CO. Global analysis of the SAXS/WAXS patterns recovered time-independent scattering fingerprints for four intermediate states of Mb. These SAXS/WAXS fingerprints provide stringent constraints for putative models of conformational states and structural transitions between them.
C1 [Cho, Hyun Sun; Dashdorj, Naranbaatar; Schotte, Friedrich; Anfinrud, Philip] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Graber, Timothy; Henning, Robert] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
RP Anfinrud, P (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM anfinrud@nih.gov
FU BioCARS; CARS; US Department of Energy, Basic Energy Sciences, Office of
Science [DE-AC02-06CH11357]; National Institutes of Health (NIH),
National Center for Research Resources [RR007707]; NIH, National
Institute of Diabetes and Digestive and Kidney Diseases
FX We thank John Olson and Jayashree Soman for supplying sperm whale
myoglobin; William A. Eaton, Eric Henry, and Gerhard Hummer for helpful
discussions; and Bernard Howder, Jr. for machining many of the
components required for this study. We thank Efim Gluskin and his group
for reconfiguring and installing two short-period undulators on the
ID14B BioCARS beamline. We thank Keith Moffat, Vukica Srajer, Harold
Brewer, Guy Macha, and other members of the BioCARS and CARS
organizations for their support during our collaboration to develop the
infrastructure required to pursue picosecond time-resolved x-ray studies
at BioCARS. Use of the Advanced Photon Source was supported by the US
Department of Energy, Basic Energy Sciences, Office of Science, under
Contract DE-AC02-06CH11357. Use of the BioCARS Sector 14 was supported
by the National Institutes of Health (NIH), National Center for Research
Resources, under Grant RR007707. This research was supported in part by
the Intramural Research Program of the NIH, National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 33
TC 71
Z9 71
U1 2
U2 38
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7281
EP 7286
DI 10.1073/pnas.1002951107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300034
PM 20406909
ER
PT J
AU Wang, LF
Jin, QH
Lee, JE
Su, IH
Ge, K
AF Wang, Lifeng
Jin, Qihuang
Lee, Ji-Eun
Su, I-hsin
Ge, Kai
TI Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate
adipogenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epigenetics; histone methylation; polycomb; PRC2
ID POLYCOMB TARGET GENES; EMBRYONIC STEM-CELLS; H3 LYSINE 27; DEVELOPMENTAL
REGULATORS; METHYLATION; DIFFERENTIATION; EXPRESSION; PLURIPOTENCY;
MECHANISMS; COMPLEX-2
AB Wnt/beta-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase Ezh2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of Ezh2 in adipogenesis, remain unclear. Here we show Ezh2 and its H3K27 methyltransferase activity are required for adipogenesis. Ezh2 directly represses Wnt1, -6, -10a, and -10b genes in preadipocytes and during adipogenesis. Deletion of Ezh2 eliminates H3K27me3 on Wnt promoters and derepresses Wnt expression, which leads to activation of Wnt/beta-catenin signaling and inhibition of adipogenesis. Ectopic expression of the wild-type (WT) Ezh2, but not the enzymatically inactive F667I mutant, prevents the loss of H3K27me3 and the defects in adipogenesis in Ezh2(-/-) preadipocytes. The adipogenesis defects in Ezh2(-/-) cells can be rescued by expression of adipogenic transcription factors PPAR gamma, C/EBP alpha, or inhibitors of Wnt/beta-catenin signaling. Interestingly, Ezh2(-/-) cells show marked increase of H3K27 acetylation globally as well as on Wnt promoters. These results indicate that H3K27 methyltransferase Ezh2 directly represses Wnt genes to facilitate adipogenesis and suggest that acetylation and trimethylation on H3K27 play opposing roles in regulating Wnt expression.
C1 [Wang, Lifeng; Jin, Qihuang; Lee, Ji-Eun; Ge, Kai] NIDDKD, Nucl Receptor Biol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Su, I-hsin] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10065 USA.
RP Ge, K (reprint author), NIDDKD, Nucl Receptor Biol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM kaig@niddk.nih.gov
RI Lee, Ji-Eun/F-7891-2011; Wang, Lifeng/I-4888-2012; Su,
I-hsin/A-2207-2011;
OI Lee, Ji-Eun/0000-0002-3768-7016; Wang, Lifeng/0000-0003-4752-6547; Su,
I-hsin/0000-0002-5894-9580; Ge, Kai/0000-0002-7442-5138
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX We thank A. Tarakhovsky for kindly providing Ezh2flox/flox
mice, O. MacDougald for dnTCF4 cDNA, Y. Tseng and Y.-W. Cho for help on
brown preadipocyte immortalization, and Z. Wang and K. Zhao for
validated histone modification antibodies. This work was supported by
the Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health to K.
G.
NR 26
TC 88
Z9 92
U1 7
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7317
EP 7322
DI 10.1073/pnas.1000031107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300040
PM 20368440
ER
PT J
AU Chen, W
Stambolian, D
Edwards, AO
Branham, KE
Othman, M
Jakobsdottir, J
Tosakulwong, N
Pericak-Vance, MA
Campochiaro, PA
Klein, ML
Tan, PL
Conley, YP
Kanda, A
Kopplin, L
Li, YM
Augustaitis, KJ
Karoukis, AJ
Scott, WK
Agarwal, A
Kovach, JL
Schwartz, SG
Postel, EA
Brooks, M
Baratz, KH
Brown, WL
Brucker, AJ
Orlin, A
Brown, G
Ho, A
Regillo, C
Donoso, L
Tian, LF
Kaderli, B
Hadley, D
Hagstrom, SA
Peachey, NS
Klein, R
Klein, BEK
Gotoh, N
Yamashiro, K
Ferris, F
Fagerness, JA
Reynolds, R
Farrer, LA
Kim, IK
Miller, JW
Corton, M
Carracedo, A
Sanchez-Salorio, M
Pugh, EW
Doheny, KF
Brion, M
DeAngelis, MM
Weeks, DE
Zack, DJ
Chew, EY
Heckenlively, JR
Yoshimura, N
Iyengar, SK
Francis, PJ
Katsanis, N
Seddon, JM
Haines, JL
Gorin, MB
Abecasis, GR
Swaroop, A
AF Chen, Wei
Stambolian, Dwight
Edwards, Albert O.
Branham, Kari E.
Othman, Mohammad
Jakobsdottir, Johanna
Tosakulwong, Nirubol
Pericak-Vance, Margaret A.
Campochiaro, Peter A.
Klein, Michael L.
Tan, Perciliz L.
Conley, Yvette P.
Kanda, Atsuhiro
Kopplin, Laura
Li, Yanming
Augustaitis, Katherine J.
Karoukis, Athanasios J.
Scott, William K.
Agarwal, Anita
Kovach, Jaclyn L.
Schwartz, Stephen G.
Postel, Eric A.
Brooks, Matthew
Baratz, Keith H.
Brown, William L.
Brucker, Alexander J.
Orlin, Anton
Brown, Gary
Ho, Allen
Regillo, Carl
Donoso, Larry
Tian, Lifeng
Kaderli, Brian
Hadley, Dexter
Hagstrom, Stephanie A.
Peachey, Neal S.
Klein, Ronald
Klein, Barbara E. K.
Gotoh, Norimoto
Yamashiro, Kenji
Ferris, Frederick, III
Fagerness, Jesen A.
Reynolds, Robyn
Farrer, Lindsay A.
Kim, Ivana K.
Miller, Joan W.
Corton, Marta
Carracedo, Angel
Sanchez-Salorio, Manuel
Pugh, Elizabeth W.
Doheny, Kimberly F.
Brion, Maria
DeAngelis, Margaret M.
Weeks, Daniel E.
Zack, Donald J.
Chew, Emily Y.
Heckenlively, John R.
Yoshimura, Nagahisa
Iyengar, Sudha K.
Francis, Peter J.
Katsanis, Nicholas
Seddon, Johanna M.
Haines, Jonathan L.
Gorin, Michael B.
Abecasis, Goncalo R.
Swaroop, Anand
CA Complications Age-Related Macular
TI Genetic variants near TIMP3 and high-density lipoprotein-associated loci
influence susceptibility to age-related macular degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genome-wide association study; single nucleotide polymorphism
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; RISK-FACTORS; DISEASE;
POLYMORPHISM; MACULOPATHY; COMMON; METAANALYSIS; DEPOSITS; DRUSEN
AB We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.
C1 [Chen, Wei; Li, Yanming; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Edwards, Albert O.; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.] Mayo Clin, Rochester, MN 55906 USA.
[Branham, Kari E.; Othman, Mohammad; Augustaitis, Katherine J.; Karoukis, Athanasios J.; Heckenlively, John R.] Univ Michigan, Ann Arbor, MI 48105 USA.
[Jakobsdottir, Johanna; Conley, Yvette P.; Weeks, Daniel E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Pericak-Vance, Margaret A.; Scott, William K.; Kovach, Jaclyn L.; Schwartz, Stephen G.] Univ Miami, Miller Sch Med, Miami, FL USA.
[Campochiaro, Peter A.; Tan, Perciliz L.; Zack, Donald J.; Katsanis, Nicholas] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Kanda, Atsuhiro; Brooks, Matthew] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
[Kopplin, Laura; Hagstrom, Stephanie A.; Peachey, Neal S.; Iyengar, Sudha K.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Agarwal, Anita; Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
[Postel, Eric A.] Duke Univ, Med Ctr, Durham, NC 27705 USA.
[Complications Age-Related Macular] Univ Penn, CAPT Coordinating Ctr, Philadelphia, PA 19104 USA.
[Brown, Gary; Ho, Allen; Regillo, Carl] Mid Atlantic Retina, Cherry Hill, NJ 08002 USA.
[Brown, Gary; Ho, Allen; Regillo, Carl] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Donoso, Larry] Philadelphia Retina Endowment Fund, Philadelphia, PA 19107 USA.
[Hagstrom, Stephanie A.; Peachey, Neal S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Peachey, Neal S.] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH 44106 USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Gotoh, Norimoto; Yamashiro, Kenji; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan.
[Fagerness, Jesen A.] Massachusetts Gen Hosp, Cambridge, MA 02114 USA.
[Fagerness, Jesen A.] Broad Inst, Cambridge, MA 02114 USA.
[Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Boston, MA 02111 USA.
[Farrer, Lindsay A.] Boston Univ, Boston, MA 02215 USA.
[Kim, Ivana K.; Miller, Joan W.; DeAngelis, Margaret M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Corton, Marta; Brion, Maria] Complexo Hosp Univ Santiago, Santiago De Compostela 15706, Spain.
[Corton, Marta; Carracedo, Angel; Brion, Maria] Univ Santiago de Compostela, Santiago De Compostela 15705, Spain.
[Sanchez-Salorio, Manuel] Inst Gallego Oftalmol, Santiago De Compostela 15706, Spain.
[Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD 21287 USA.
[Seddon, Johanna M.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Gorin, Michael B.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
RP Abecasis, GR (reprint author), Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
EM goncalo@umich.edu; swaroopa@nei.nih.gov
RI Peachey, Neal/G-5533-2010; Abecasis, Goncalo/B-7840-2010; Weeks,
Daniel/B-2995-2012; Haines, Jonathan/C-3374-2012; Katsanis,
Nicholas/E-1837-2012; DeAngelis, e/J-7863-2015
OI Klein, Ronald/0000-0002-4428-6237; Weeks, Daniel/0000-0001-9410-7228;
Katsanis, Nicholas/0000-0002-2480-0171; Farrer,
Lindsay/0000-0001-5533-4225; Brion, Maria/0000-0001-7463-2148; Zack,
Don/0000-0002-7966-1973; Abecasis, Goncalo/0000-0003-1509-1825; Swaroop,
Anand/0000-0002-1975-1141; Carracedo, Angel/0000-0003-1085-8986;
FU National Eye Institute; National Institutes of Health [EY016862,
EY007758, EY09859, EY012118, P30-EY014801, EY-014458, EY014467,
HL084729, HG002651, HHSN268200782096C]; Foundation Fighting Blindness;
Macula Vision Research Foundation; American Health Assistance
Foundation; Research to Prevent Blindness; Pew Charitable Trusts; Mayo
Clinic Foundation; Casey Macular Degeneration Center; Marion W. and
Edward F. Knight AMD Fund; Harold and Pauline Price Foundation; National
Genotyping Centre of Spain; Elmer and Sylvia Sramek Foundation; Center
for Inherited Disease Research
FX We thank numerous clinicians, clinical staff, patients, and their
families for their participation in and dedication to the project; the
Kellogg Eye Center AMD group, the Complications of Age-Related Macular
Degeneration Prevention Trial consortium, the Spanish AMD research
group, staff at the National Center for Biotechnology Information, and
Dr. Hemin Chin; and the Tufts Medical Center/Massachusetts General
Hospital group for sharing genome-wide association results. This
research was supported in part by the intramural program of the National
Eye Institute and by National Institutes of Health Grants EY016862,
EY007758, EY09859, EY012118, P30-EY014801, EY-014458, EY014467,
HL084729, and HG002651, by the Foundation Fighting Blindness, the Macula
Vision Research Foundation, the American Health Assistance Foundation,
Research to Prevent Blindness, the Pew Charitable Trusts, the Mayo
Clinic Foundation, the Casey Macular Degeneration Center Fund, the
Marion W. and Edward F. Knight AMD Fund, the Harold and Pauline Price
Foundation, National Genotyping Centre of Spain, and the Elmer and
Sylvia Sramek Foundation. The Center for Inherited Disease Research,
fully funded through a federal contract (HHSN268200782096C) from
National Institutes of Health to The Johns Hopkins University, performed
genotyping of the discovery cohort.
NR 36
TC 261
Z9 266
U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7401
EP 7406
DI 10.1073/pnas.0912702107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300054
PM 20385819
ER
PT J
AU Love, DC
Ghosh, S
Mondoux, MA
Fukushige, T
Wang, P
Wilson, MA
Iser, WB
Wolkow, CA
Krause, MW
Hanover, JA
AF Love, Dona C.
Ghosh, Salil
Mondoux, Michelle A.
Fukushige, Tetsunari
Wang, Peng
Wilson, Mark A.
Iser, Wendy B.
Wolkow, Catherine A.
Krause, Michael W.
Hanover, John A.
TI Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes
regulating longevity, stress, and immunity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diabetes; genomics; polycomb; epigenetics; transcription
ID LINKED N-ACETYLGLUCOSAMINE; C-ELEGANS; INSULIN-RESISTANCE; LIFE-SPAN;
NUCLEOCYTOPLASMIC GLYCOSYLATION; HEXOSAMINE BIOSYNTHESIS;
MONOCLONAL-ANTIBODIES; X-CHROMOSOME; PROTEIN; GLCNACYLATION
AB Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.
C1 [Love, Dona C.; Ghosh, Salil; Mondoux, Michelle A.; Fukushige, Tetsunari; Wang, Peng; Krause, Michael W.; Hanover, John A.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Wilson, Mark A.; Iser, Wendy B.; Wolkow, Catherine A.] NIA, NIH, Baltimore, MD 21224 USA.
RP Hanover, JA (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
OI Krause, Michael/0000-0001-6127-3940
FU NIH; NIDDK; NIA
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK, and NIA.
NR 67
TC 72
Z9 73
U1 4
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7413
EP 7418
DI 10.1073/pnas.0911857107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300056
PM 20368426
ER
PT J
AU Liang, XJ
Meng, H
Wang, YZ
He, HY
Meng, J
Lu, J
Wang, PC
Zhao, YL
Gao, XY
Sun, BY
Chen, CY
Xing, GM
Shen, DW
Gottesman, MM
Wu, Y
Yin, JJ
Jia, L
AF Liang, Xing-Jie
Meng, Huan
Wang, Yingze
He, Haiyong
Meng, Jie
Lu, Juan
Wang, Paul C.
Zhao, Yuliang
Gao, Xueyun
Sun, Baoyun
Chen, Chunying
Xing, Genmei
Shen, Dingwu
Gottesman, Michael M.
Wu, Yan
Yin, Jun-jie
Jia, Lee
TI Metallofullerene nanoparticles circumvent tumor resistance to cisplatin
by reactivating endocytosis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug resistance; nanomedicine; nanoimaging; chemotherapy;
nanopharmaceutical
ID OVARIAN-CARCINOMA CELLS; CHROMATOGRAPHY-MASS SPECTROMETRY; MRI CONTRAST
AGENTS; CELLULAR ACCUMULATION; MULTIDRUG-RESISTANCE; REDUCED EXPRESSION;
CANCER-CELLS; LINES; PLATINUM; IDENTIFICATION
AB Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C(82)(OH)(22)](n) nanoparticles, that [Gd@C(82)(OH)(22)](n) may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C(82)(OH)(22)](n) not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CP-r PC-3-luc cells with [Gd@C(82)(OH)(22)](n) enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C(82)(OH)(22)](n) nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.
C1 [Liang, Xing-Jie; Wang, Yingze; He, Haiyong; Meng, Jie; Lu, Juan; Chen, Chunying; Wu, Yan] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China.
[Meng, Huan; Meng, Jie; Zhao, Yuliang; Gao, Xueyun; Sun, Baoyun; Xing, Genmei] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Inst High Energy Phys, Beijing 100049, Peoples R China.
[Wang, Paul C.] Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20060 USA.
[Shen, Dingwu; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Yin, Jun-jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Jia, Lee] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Liang, XJ (reprint author), Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China.
EM liangxj@nanoctr.cn; zhaoyuliang@mail.ihep.ac.cn
RI Yin, Jun Jie /E-5619-2014
FU China-Finland Nanotechnology [2008DFA01510]; Chinese Academy of Sciences
(CAS) [07165111ZX]; 973 program [2006CB705600]; National Basic Research
Program of China [2009CB930200]; National Center for Research Resources,
National Institutes of Health [2 G12 RR003048]
FX We appreciate George Leiman for editing the manuscript. We are also
grateful to Dr. Wayne Wamer (Center for Food Safety & Applied
Nutrition/US Food and Drug Administration) for his significant input in
this study. This work is financially supported by the Project of
China-Finland Nanotechnology (2008DFA01510) the Chinese Academy of
Sciences (CAS) "Hundred Talents Program" (07165111ZX), the 973 program
(2006CB705600), and the National Basic Research Program of China
(2009CB930200). This work was partially supported by Grant 2 G12
RR003048 from the Research Centers in Minority Institutions Program,
National Center for Research Resources, National Institutes of Health.
NR 51
TC 132
Z9 137
U1 9
U2 90
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7449
EP 7454
DI 10.1073/pnas.0909707107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300062
PM 20368438
ER
PT J
AU Karabanov, A
Cervenka, S
de Manzano, O
Forssberg, H
Farde, L
Ullen, F
AF Karabanov, Anke
Cervenka, Simon
de Manzano, Orjan
Forssberg, Hans
Farde, Lars
Ullen, Fredrik
TI Dopamine D2 receptor density in the limbic striatum is related to
implicit but not explicit movement sequence learning
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE basal ganglia; PET; plasticity; procedural learning
ID POSITRON-EMISSION-TOMOGRAPHY; PROCESS DISSOCIATION PROCEDURE; BASAL
GANGLIA; INDIVIDUAL-DIFFERENCES; SYNAPTIC PLASTICITY; D2-RECEPTOR
BINDING; ACTION REPERTOIRES; HUMAN BRAIN; PET; PERFORMANCE
AB A large body of literature suggests that motor sequence learning involves dopamine-modulated plastic processes in the basal ganglia. Sequence learning can occur both implicitly, without conscious awareness and intention to learn, and explicitly, i.e., under conscious control. Here, we investigated whether individual differences in implicit and explicit sequence learning of movement sequences in a group of 15 healthy participants are related to dopamine D2 receptor densities in functional subregions of the striatum. Sequence learning was assessed using the serial reaction time task, and measures of implicit and explicit knowledge were estimated using a process dissociation procedure. Correlation analyses were performed between these measures and D2 receptor densities, which had been measured previously with positron emission tomography. Striatal D2 densities were negatively related to measures of sequence learning. In the limbic subregion, D2 densities were specifically related to implicit but not explicit learning. These findings suggest that individual differences in striatal DA function underlie differences in sequence learning ability and support that implicit and explicit sequence learning depend on partly distinct neural circuitry. The findings are also in line with the general view that implicit learning systems are evolutionarily primitive and tend to rely more on phylogenetically old neural circuitry than does explicit learning and cognition.
C1 [Karabanov, Anke; de Manzano, Orjan; Forssberg, Hans; Ullen, Fredrik] Karolinska Inst, Neuropediat Res Unit Q2 07, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden.
[Karabanov, Anke; Cervenka, Simon; de Manzano, Orjan; Forssberg, Hans; Farde, Lars; Ullen, Fredrik] Karolinska Inst, Stockholm Brain Inst, SE-17176 Stockholm, Sweden.
[Karabanov, Anke] Natl Inst Neurol Disorders & Stroke, Human Motor Control Unit, NIH, Bethesda, MD 20892 USA.
[Cervenka, Simon; Farde, Lars] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.
RP Karabanov, A (reprint author), Karolinska Inst, Neuropediat Res Unit Q2 07, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden.
EM anke.karabanov@ki.se
OI de Manzano, Orjan/0000-0002-4632-1112; Forssberg,
Hans/0000-0003-2069-6618; Karabanov, Anke Ninija/0000-0003-1874-393X;
Cervenka, Simon/0000-0001-8103-6977
FU Swedish Research Council; Swedish Governmental Agency for Innovation
Systems (Vinnova); Karolinska Institute/National Institutes of Health
FX This work was supported by the Swedish Research Council, the Swedish
Governmental Agency for Innovation Systems (Vinnova), and the Karolinska
Institute/National Institutes of Health Graduate Partnership Program.
NR 62
TC 31
Z9 31
U1 5
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 20
PY 2010
VL 107
IS 16
BP 7574
EP 7579
DI 10.1073/pnas.0911805107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FU
UT WOS:000276892300083
PM 20368439
ER
PT J
AU Adamson, CS
Sakalian, M
Salzwedel, K
Freed, EO
AF Adamson, Catherine S.
Sakalian, Michael
Salzwedel, Karl
Freed, Eric O.
TI Polymorphisms in Gag spacer peptide 1 confer varying levels of
resistance to the HIV-1 maturation inhibitor bevirimat
SO RETROVIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLEAVAGE SITES; PARTICLE MATURATION;
HEALTHY-VOLUNTEERS; BETULINIC ACID; PA-457; PROTEASE; POLYPROTEIN;
SAFETY; STEP
AB Background: The maturation inhibitor bevirimat (BVM) potently inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking capsid-spacer peptide 1 (CA-SP1) cleavage. Recent clinical trials demonstrated that a significant proportion of HIV-1-infected patients do not respond to BVM. A patient's failure to respond correlated with baseline polymorphisms at SP1 residues 6-8.
Results: In this study, we demonstrate that varying levels of BVM resistance are associated with point mutations at these residues. BVM susceptibility was maintained by SP1-Q6A, -Q6H and -T8A mutations. However, an SP1-V7A mutation conferred high-level BVM resistance, and SP1-V7M and T8 Delta mutations conferred intermediate levels of BVM resistance.
Conclusions: Future exploitation of the CA-SP1 cleavage site as an antiretroviral drug target will need to overcome the baseline variability in the SP1 region of Gag.
C1 [Adamson, Catherine S.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Sakalian, Michael; Salzwedel, Karl] Panacos Pharmaceut Inc, Gaithersburg, MD 20877 USA.
[Adamson, Catherine S.] Univ St Andrews, Bute Med Sch, St Andrews KY16 9TS, Fife, Scotland.
RP Adamson, CS (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM catherine.adamson@st-andrews.ac.uk
FU Center for Cancer Research, National Cancer Institute, NIH; Intramural
AIDS Targeted Antiviral Program
FX We thank members of the Freed laboratory for helpful discussions and
critical review of the manuscript. We acknowledge the NIH AIDS Reagent
Program for providing HIV-Ig and TZM-bl cells. This research was
supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, NIH and by the Intramural AIDS
Targeted Antiviral Program.
NR 37
TC 35
Z9 35
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD APR 20
PY 2010
VL 7
AR 36
DI 10.1186/1742-4690-7-36
PG 8
WC Virology
SC Virology
GA 605EQ
UT WOS:000278330800001
PM 20406463
ER
PT J
AU Hutchins, BI
AF Hutchins, B. Ian
TI Competitive Outgrowth of Neural Processes Arising from Long-Distance
cAMP Signaling
SO SCIENCE SIGNALING
LA English
DT Review
ID HIPPOCAMPAL-NEURONS; GROWTH CONES; POLARITY; ESTABLISHMENT; TRANSIENTS
AB During development, competition among undifferentiated neurites results in the growth of one neurite at the expense of the rest. This neurite becomes the axon. A similar competitive mechanism later governs the differential outgrowth of the axon and its branches. A long-range signal between different parts of the neuron is required to mediate this competition, but the nature of this signal was unknown. Recent work has shown that local cyclic adenosine monophosphate (cAMP) signaling promotes neurite growth but leads to decreased cAMP concentrations in distant neurites, thereby inhibiting their growth. The precise mechanism mediating long-distance cyclic nucleotide signaling is unclear but may involve localized calcium transients and autocrine signaling. Mutually inhibitory, competitive interactions during outgrowth of neural processes can emerge from these signaling events, both during axon specification and later during axon branching.
C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Hutchins, BI (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM bruce.hutchins@nih.gov
RI Hutchins, Ian/A-5713-2009
OI Hutchins, Ian/0000-0001-7657-552X
FU Intramural NIH HHS [ZIA NS002824-21]
NR 15
TC 14
Z9 14
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD APR 20
PY 2010
VL 3
IS 118
AR jc1
DI 10.1126/scisignal.3118jc1
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 585YX
UT WOS:000276868000001
PM 20407121
ER
PT J
AU Ko, SU
Stenholm, S
Ferrucci, L
AF Ko, Seung-uk
Stenholm, Sari
Ferrucci, Luigi
TI Characteristic gait patterns in older adults with obesity-Results from
the Baltimore Longitudinal Study of Aging
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Gait; Obesity; Gait speed; Mechanical work expenditure; BMI
ID CENTER LOCATION; KNEE; OSTEOARTHRITIS; HIP; AGE; WALKING; JOINT;
ASSOCIATION; DISABILITY; OVERWEIGHT
AB Obesity in older adults is a growing public health problem. Excess weight causes biomechanical burden to lower extremity joints and contribute to joint pathology. The aim of this study was to identify specific characteristics of gait associated with body mass index (BMI). Preferred and maximum speed walking and related gait characteristics were examined in 164 (50-84 years) participants from Baltimore Longitudinal Study of Aging (BLSA) able to walk unassisted. Participants were divided into three groups based on their BMI: normal weight (19 <= BMI <25 kg/m(2)), overweight (25 <= BMI <30 kg/m(2)) and obese (BMI 30 <= BMI <40 kg/m(2)). Total ankle generative mechanical work expenditure (MWE) in the anterior-posterior (AP) plane was progressively and significantly lower with increase in BMI for both preferred (p=0.026) and maximum speed walking (p<0.001). In the medial-lateral (ML) plane, total knee generative MWE was higher in obese participants in the preferred speed task (p=0.002), and total hip absorptive MWE was higher in obese in both preferred speed (p < 0.001) and maximum speed (p=0.002) walking task compared to the normal weight participants. Older adults with obesity show spatiotemporal gait patterns that may help in reducing contact impacts. In addition, in obese persons mechanical energy usages tend to be lower in the AP plane and higher in the ML plane. Since forward progression forces are mainly implicated in normal walking, this pattern found in obese participants is suggestive of lower energetic efficiency. Published by Elsevier Ltd.
C1 [Ko, Seung-uk; Stenholm, Sari; Ferrucci, Luigi] NIA, Clin Res Branch, Harbor Hosp, Baltimore, MD 21225 USA.
[Stenholm, Sari] Natl Inst Hlth & Welf, Helsinki, Finland.
RP Ko, SU (reprint author), NIA, Clin Res Branch, Harbor Hosp, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM kos2@mail.nih.gov
RI Sriwisit, Sukhumaphorn/G-1405-2011; Stenholm, Sari/G-6940-2011;
Agaliotis, Maria/G-5334-2012
FU NIH; National Institute on Aging and Finnish Academy [125494 SS]
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging and Finnish Academy (No. 125494
SS). Data for these analyses were obtained from the Baltimore
Longitudinal Study of Aging, a study performed by the National Institute
on Aging.
NR 25
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U1 2
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
J9 J BIOMECH
JI J. Biomech.
PD APR 19
PY 2010
VL 43
IS 6
BP 1104
EP 1110
DI 10.1016/j.jbiomech.2009.12.004
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 593PK
UT WOS:000277471200013
PM 20080238
ER
PT J
AU Negussie, AH
Miller, JL
Reddy, G
Drake, SK
Wood, BJ
Dreher, MR
AF Negussie, Ayele H.
Miller, Jenna L.
Reddy, Goutham
Drake, Steven K.
Wood, Bradford J.
Dreher, Matthew R.
TI Synthesis and in vitro evaluation of cyclic NGR peptide targeted
thermally sensitive liposome
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE cNGR; Angiogenesis; Liposome; Tumor; CD13/APN
ID FOLATE-BINDING-PROTEIN; TUMOR-NECROSIS-FACTOR; AMINOPEPTIDASE-N;
ANTI-HER2 IMMUNOLIPOSOMES; DRUG-DELIVERY; ANGIOGENESIS; CANCER;
RECEPTOR; VASCULATURE; DOXORUBICIN
AB The Asn-Gly-Arg (NGR) motif in both cyclic and linear form has previously been shown to specifically bind to CD13/aminopeptidase N that is selectively overexpressed in tumor vasculature and some tumor cells. However, previous versions of cyclic NGR used a liable disulfide bridge between cysteine residues that may be problematic for liposome targeting due to disulfide bond formation between adjacent peptides on the liposomal surface. In this study, we report the design, synthesis, and characterization of a novel cyclic NGR-containing peptide, cKNGRE, which does not contain a disulfide bridge. cKNGRE was synthesized in good yield and purity and attached to the fluorescent reporter Oregon Green (cKNGRE-OG) and lysolipid-containing temperature sensitive liposomes (LTSLs). The identity of cKNGRE was verified with NMR and mass spectral techniques. In vitro fluorescence microscopy evaluation of cKNGRE-OG demonstrated binding and active uptake by CD13(+) cancer cells and minimal binding to CD13(-) cancer cells. The cKNGRE-OG ligand displayed 3.6-fold greater affinity for CD13(+) cancer cells than a linear NGR-containing peptide. Affinity for CD13(+) cancer cells was similarly improved 10-fold for both the cyclic and linear NGR when presented in a multivalent fashion on the surface of an LTSL cKNGRE-targeted LTSLs rapidly released (>75% in <4 s) doxorubicin at 41.3 degrees C with minimal release at 37 degrees C. These results demonstrate the ability to synthesize a cKNGRE-targeted temperature sensitive liposome that lacks a disulfide bridge and has sufficient binding affinity for biological applications. Published by Elsevier B.V.
C1 [Drake, Steven K.; Dreher, Matthew R.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Dreher, MR (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike,Bldg 10,Rm 1C636X,MSC 1182, Bethesda, MD 20892 USA.
EM dreherm@cc.nih.gov
FU National Institutes of Health
FX This research supported in part by the Intramural Research Program of
the National Institutes of Health. We thank Dr. Edyta Pawelczyk and Dr.
Elaine Kay Jordan for assistance with flow cytometry, and Dr. Herman Yeh
and Mr. Wesley White for 1H NMR (600 MHz) experiments.
NR 56
TC 69
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U1 6
U2 54
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD APR 19
PY 2010
VL 143
IS 2
BP 265
EP 273
DI 10.1016/j.jconrel.2009.12.031
PG 9
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 590IP
UT WOS:000277219200014
PM 20067811
ER
PT J
AU Khattar, SK
Collins, PL
Samal, SK
AF Khattar, Sunil K.
Collins, Peter L.
Samal, Siba K.
TI Immunization of cattle with recombinant Newcastle disease virus
expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal
and serum antibody responses and provides partial protection against
BHV-1
SO VACCINE
LA English
DT Article
DE NDV; BHV-1 gD; Antibody responses
ID VESICULAR STOMATITIS VIRUSES; RESPIRATORY SYNCYTIAL VIRUS; HUMAN
ADENOVIRUS TYPE-5; IMMUNE-RESPONSE; NEUTRALIZING ANTIBODIES; VECTORED
VACCINE; INFLUENZA-VIRUS; CELL RESPONSES; NATURAL HOST; FOREIGN GENE
AB Bovine herpesvirus-1 (BHV-1) is a major cause of respiratory tract diseases in cattle. Vaccination of cattle against BHV-1 is a high priority. A major concern of currently modified live BHV-1 vaccines is their ability to cause latent infection and subsequent reactivation resulting in many outbreaks. Thus, there is a need for alternative strategies. We generated two recombinant Newcastle disease viruses (NDVs) expressing the glycoprotein D (gD) of BHV-1 from an added gene. One recombinant, rLaSota/gDFL, expressed gD without any modification. The other recombinant, rLaSota/gDF, expressed a chimeric gD in which the ectodomain of gD was fused with the transmembrane domain and cytoplasmic tail of the NDV fusion F glycoprotein. Remarkably, the native gD expressed by rLaSota/gDFL virus was incorporated into the NDV virion 2.5-fold more efficiently than the native NDV proteins, whereas the chimeric gD was not detectably incorporated even though it was abundantly expressed on the infected cell surface. The expression of gD did not increase the virulence of the rNDV vectors in chickens. A single intranasal and intratracheal inoculation of calves with either recombinant NDV elicited mucosal and systemic antibodies specific to BHV-1, with the responses to rLaSota/gDFL being higher than those to rLaSota/gDF. Following challenge with BHV-1, calves immunized with the recombinant NDVs had lower titers and earlier clearance of challenge virus compared to the empty vector control, and reduced disease was observed with rLaSota/gDFL Following challenge, the titers of serum antibodies specific to BHV-1 were higher in the animals immunized with the rNDV vaccines compared to the rNDV parent virus, indicating that the vaccines primed for secondary responses. Our data suggest that NDV can be used as a vaccine vector in bovines and that BHV-1 gD may be useful in mucosal vaccine against BHV-1 infection, but might require augmentation by a second dose or the inclusion of additional BHV-1 antigens. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Khattar, Sunil K.; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX We thank Daniel Rockemann and all our laboratory members for their
excellent technical assistance and help.; This research was supported in
part by NIAID contract no. N01A060009 (85% support) and the NIAID, NIH
Intramural Research Program (15% support).; The views expressed herein
do not necessarily reflect the official policies of the Department of
Health and Human Services; nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.
NR 61
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U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD APR 19
PY 2010
VL 28
IS 18
BP 3159
EP 3170
DI 10.1016/j.vaccine.2010.02.051
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 588JA
UT WOS:000277064500013
PM 20189484
ER
PT J
AU Bruder, JT
Stefaniak, ME
Patterson, NB
Chen, P
Konovalova, S
Limbach, K
Campo, JJ
Ettyreddy, D
Li, S
Dubovsky, F
Richie, TL
King, CR
Long, CA
Doolan, DL
AF Bruder, Joseph T.
Stefaniak, Maureen E.
Patterson, Noelle B.
Chen, Ping
Konovalova, Svetlana
Limbach, Keith
Campo, Joseph J.
Ettyreddy, Damodar
Li, Sheng
Dubovsky, Filip
Richie, Thomas L.
King, C. Richter
Long, Carole A.
Doolan, Denise L.
TI Adenovectors induce functional antibodies capable of potent inhibition
of blood stage malaria parasite growth
SO VACCINE
LA English
DT Article
DE Malaria; Adenovirus vaccines; Adenovector; Blood stage; Functional
antibodies; Growth inhibition assay (GIA)
ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1;
PLASMODIUM-FALCIPARUM MALARIA; PROTECTS AOTUS MONKEYS; INNATE
IMMUNE-RESPONSE; C-TERMINAL FRAGMENT; VACCINE CANDIDATE; HIV-1 VACCINE;
CELL-LINE; IN-VITRO
AB An effective malaria vaccine remains a global health priority. Recombinant adenoviruses are a promising vaccine platform, and Plasmodium falciparum apical membrane antigen 1 (AMA1) and merozoite surface protein 1-42 (MSP1(42)) are leading blood stage vaccine candidates. We evaluated the importance of surface antigen localization and glycosylation on the immunogenicity of adenovector delivered AMA1 and MSP1(42) and assessed the ability of these vaccines to induce functional antibody responses capable of inhibiting parasite growth in vitro. Adenovector delivery induced unprecedented levels of biologically active antibodies in rabbits as indicated by the parasite growth inhibition assay. These responses were as potent as published results using any other vaccine system, including recombinant protein in adjuvant. The cell surface associated and glycosylated forms of AMA1 and MSP1(42) elicited 99% and 60% inhibition of parasite growth, respectively. Antigens that were expressed at the cell surface and glycosylated were much better than intracellular antigens at inducing antibody responses. Good T cell responses were observed for all forms of AMA1 and MSP1(42). Antigen-specific antibody responses, but typically not T cell responses, were boosted by a second administration of adenovector. These data highlight the importance of rational vaccine design and support the advancement of adenovector delivery technology for a malaria vaccine. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Bruder, Joseph T.; Chen, Ping; Konovalova, Svetlana; Ettyreddy, Damodar; King, C. Richter] GenVec Inc, Gaithersburg, MD 20878 USA.
[Stefaniak, Maureen E.; Patterson, Noelle B.; Limbach, Keith; Campo, Joseph J.; Richie, Thomas L.; Doolan, Denise L.] USN, Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD 20910 USA.
[Li, Sheng; Dubovsky, Filip] Malaria Vaccine Initiat, PATH, Bethesda, MD 20814 USA.
[Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Doolan, Denise L.] PO Royal Melbourne Hosp, Queensland Inst Med Res, Bancroft Ctr, Brisbane, Qld 4029, Australia.
RP Bruder, JT (reprint author), GenVec Inc, 65 W Watkins Mill Rd, Gaithersburg, MD 20878 USA.
EM jbruder@genvec.com
RI Doolan, Denise/F-1969-2015;
OI Richie, Thomas/0000-0002-2946-5456
FU GenVec Inc.; NMRC; U.S. Army Medical Research & Material Command;
PATH/Malaria Vaccine Initiative; Pfizer Australia
FX This work was supported by funds awarded to GenVec Inc. and NMRC by PATH
Malaria Vaccine Initiative, and by funds allocated to NMRC by the U.S.
Army Medical Research & Material Command (work units 6000.RAD1.F.A0309
and 62236N.4127.3696.A0258). The CIA Reference Center is supported by
the PATH/Malaria Vaccine Initiative. DLD was supported in part by a
Pfizer Australia Senior Research Fellow. The experiments reported herein
were conducted in compliance with the Animal Welfare Act and in
accordance with the principles set forth in the "Guide for the Care and
Use of Laboratory Animals," Institute of Laboratory Animals Resources,
National Research Council, National Academy Press, 1996. TLR is a
military service member and CAL an employee of the U.S. Government. This
work was prepared as part of their official duties. Title 17 U.S.C. 105
provides that 'Copyright protection under this title is not available
for any work of the United States Government.' Title 17 U.S.C. 101
defines a U.S. Government work as a work prepared by a military service
member or employee of the U.S. Government as part of that person's
official duties. The views expressed in this article are those of the
authors and do not necessarily reflect the official policy or position
of the Department of the Navy, Department of Defense, nor the U.S.
Government.
NR 53
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U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD APR 19
PY 2010
VL 28
IS 18
BP 3201
EP 3210
DI 10.1016/j.vaccine.2010.02.024
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 588JA
UT WOS:000277064500018
PM 20188680
ER
PT J
AU Wendte, JM
Miller, MA
Nandra, AK
Peat, SM
Crosbie, PR
Conrad, PA
Grigg, ME
AF Wendte, J. M.
Miller, M. A.
Nandra, A. K.
Peat, S. M.
Crosbie, P. R.
Conrad, P. A.
Grigg, M. E.
TI Limited genetic diversity among Sarcocystis neurona strains infecting
southern sea otters precludes distinction between marine and terrestrial
isolates
SO VETERINARY PARASITOLOGY
LA English
DT Article
DE Sarcocystis neurona; Sea otter (Enhydra lutris); SnSAG; Genotyping;
Population genetics
ID ENHYDRA-LUTRIS-NEREIS; EQUINE PROTOZOAL MYELOENCEPHALITIS;
PHOCA-VITULINA-RICHARDSI; TOXOPLASMA-GONDII; SURFACE-ANTIGEN;
MENINGOENCEPHALITIS; DIFFERENTIATION; POPULATION; CALIFORNIA; MORTALITY
AB Sarcocystis neurona is an apicomplexan parasite identified as a cause of fatal neurological disease in the threatened southern sea otter (Enhydra lutris nereis). In an effort to characterize virulent S. neurona strains circulating in the marine ecosystem, this study developed a range of markers relevant for molecular genotyping. Highly conserved sequences within the 18S ribosomal gene array, the plastid-encoded RNA polymerase (RPOb) and the cytochrome c oxidase subunit 1 mitochondrial gene (CO1) were assessed for their ability to distinguish isolates at the genus and species level. For within-species comparisons, five surface antigens (SnSAG1-SnSAG5) and one high resolution microsatellite marker (Sn9) were developed as genotyping markers to evaluate intra-strain diversity. Molecular analysis at multiple loci revealed insufficient genetic diversity to distinguish terrestrial isolates from strains infecting marine mammals. Furthermore, SnSAG specific primers applied against DNA from the closely related species, Sarcocystis falcatula, lead to the discovery of highly similar orthologs to SnSAG2, 3, and 4, calling into question the specificity of diagnostic tests based on these antigens. The results of this study suggest a population genetic structure for S. neurona similar to that reported for the related parasite, Toxoplasma gondii, dominated by a limited number of successful genotypes. Published by Elsevier B.V.
C1 [Wendte, J. M.; Nandra, A. K.; Grigg, M. E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wendte, J. M.] Oklahoma State Univ, Ctr Vet Hlth Sci, Dept Vet Pathobiol, Stillwater, OK 74074 USA.
[Wendte, J. M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA.
[Miller, M. A.] Marine Wildlife Vet Care & Res Ctr, Calif Dept Fish & Game, Santa Cruz, CA 95060 USA.
[Peat, S. M.; Crosbie, P. R.] Calif State Univ Fresno, Dept Biol, Fresno, CA 93740 USA.
[Peat, S. M.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Conrad, P. A.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
RP Grigg, ME (reprint author), NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM griggm@niaid.nih.gov
FU NIH; NIAID; College of Science and Mathematics; Division of Graduate
Studies, and Associated Students at California State University, Fresno
(SMP)
FX This work was supported by the Intramural Research Program of the NIH
and NIAID (MEG) and by the College of Science and Mathematics. Division
of Graduate Studies, and Associated Students at California State
University, Fresno (SMP). MEG is a scholar of the Canadian Institute for
Advanced Research (CIFAR) Program for Integrated Microbial Biodiversity.
JMW is an HHMI-NIH Research Scholar. We would like to thank the staff of
the California Department of Fish and Game Marine Wildlife Veterinary
Care and Research Center and Dr. Frances Gulland at the Marine Mammal
Center for their assistance in obtaining samples from sea otters and
harbor seals, respectively, Ann Melli and Andrea Packham for their
assistance in cultivating the parasite isolates for this study, Spencer
Magargal for initial molecular characterization, and Jose Soto for
assistance in sequence generation. Thanks to J.P. Dubey and Stephen
Raverty for kindly providing S. neurona and S. cruzi, S. campestris
isolates, respectively.
NR 43
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U1 5
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4017
J9 VET PARASITOL
JI Vet. Parasitol.
PD APR 19
PY 2010
VL 169
IS 1-2
BP 37
EP 44
DI 10.1016/j.vetpar.2009.12.020
PG 8
WC Parasitology; Veterinary Sciences
SC Parasitology; Veterinary Sciences
GA 585CE
UT WOS:000276801100006
PM 20071081
ER
PT J
AU Waybright, T
Avellino, AM
Ellenbogen, RG
Hollinger, BJ
Veenstra, TD
Morrison, RS
AF Waybright, Timothy
Avellino, Anthony M.
Ellenbogen, Richard G.
Hollinger, Bradley J.
Veenstra, Timothy D.
Morrison, Richard S.
TI Characterization of the human ventricular cerebrospinal fluid proteome
obtained from hydrocephalic patients
SO JOURNAL OF PROTEOMICS
LA English
DT Article; Proceedings Paper
CT 3rd EuPA Congress
CY JUN 14-17, 2009
CL Stockholm, SWEDEN
DE Cerebrospinal fluid; Mass spectrometry; Proteomics; Fractionation;
Ventricular CSF; Lumbar CSF
ID TANDEM MASS-SPECTROMETRY; MULTIDIMENSIONAL CHROMATOGRAPHY; BIOMARKERS;
PROTEINS; CHILDREN; DISEASE; BRAIN
AB The continuing expansion of proteomic technology has been fueled by the potential for discovering novel biomarkers that may be used for the early detection of disease. It has been proposed that human cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord from traumatic injury, may be a valuable target for the diagnosis of a variety of conditions such as Alzheimer's disease, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson's disease. The immense complexity of biofluids, however, still requires that considerable development be made in the analytical techniques used so that comprehensive coverage of the proteins present in such samples is achieved. Using a simple separation strategy the protein complement of human ventricular cerebrospinal fluid obtained from patients with hydrocephalus was evaluated. The study resulted in the identification of over 1500 unique proteins that were found within all nine CSF samples that were analyzed. Comparison with the HUPO serum proteome database demonstrated that human ventricular CSF contains a large array of proteins that may be unique to CSF. This analysis greatly increases our knowledge of the protein content of this clinically important biofluid. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Waybright, Timothy; Hollinger, Bradley J.; Veenstra, Timothy D.] NCI, SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
[Avellino, Anthony M.; Ellenbogen, Richard G.] Seattle Childrens Hosp, Dept Neurol Surg, Seattle, WA 98105 USA.
[Avellino, Anthony M.; Ellenbogen, Richard G.; Morrison, Richard S.] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA.
RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, POB B,Bldg 469,Rm 160, Frederick, MD 21702 USA.
EM veenstra@ncifcrf.gov; yael@u.washington.edu
FU NCI NIH HHS [N01-CO-12400]; NINDS NIH HHS [NS35533]
NR 21
TC 11
Z9 11
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD APR 18
PY 2010
VL 73
IS 6
SI SI
BP 1156
EP 1162
DI 10.1016/j.jprot.2010.02.004
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 597ND
UT WOS:000277763800013
PM 20176152
ER
PT J
AU Bunting, SF
Callen, E
Wong, N
Chen, HT
Polato, F
Gunn, A
Bothmer, A
Feldhahn, N
Fernandez-Capetillo, O
Cao, L
Xu, XL
Deng, CX
Finkel, T
Nussenzweig, M
Stark, JM
Nussenzweig, A
AF Bunting, Samuel F.
Callen, Elsa
Wong, Nancy
Chen, Hua-Tang
Polato, Federica
Gunn, Amanda
Bothmer, Anne
Feldhahn, Niklas
Fernandez-Capetillo, Oscar
Cao, Liu
Xu, Xiaoling
Deng, Chu-Xia
Finkel, Toren
Nussenzweig, Michel
Stark, Jeremy M.
Nussenzweig, Andre
TI 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by
Blocking Resection of DNA Breaks
SO CELL
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; DAMAGE-RESPONSE;
POLY(ADP-RIBOSE) POLYMERASE; GENOMIC INSTABILITY; CHROMOSOMAL BREAKS;
BRCA1 DEFICIENCY; VERTEBRATE CELLS; MAMMALIAN-CELLS; DIRECTED REPAIR
AB Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4. Loss of 53BP1 alleviates hypersensitivity of Brca1 mutant cells to PARP inhibition and restores error-free repair by HR. Mechanistically, 53BP1 deletion promotes ATM-dependent processing of broken DNA ends to produce recombinogenic single-stranded DNA competent for HR. In contrast, Lig4 deficiency does not rescue the HR defect in Brca1 mutant cells but prevents the joining of chromatid breaks into chromosome rearrangements. Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations.
C1 [Bunting, Samuel F.; Callen, Elsa; Wong, Nancy; Chen, Hua-Tang; Polato, Federica; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Cao, Liu; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Xu, Xiaoling; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Gunn, Amanda; Stark, Jeremy M.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Canc Biol, Duarte, CA 91010 USA.
[Gunn, Amanda; Stark, Jeremy M.] City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA.
[Bothmer, Anne; Feldhahn, Niklas; Nussenzweig, Michel] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Michel] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Fernandez-Capetillo, Oscar] Spanish Natl Canc Res Ctr CNIO, Genom Instabil Grp, Madrid 28029, Spain.
RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
RI Fernandez-Capetillo, Oscar/H-3508-2015; deng, chuxia/N-6713-2016
OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885;
FU National Institutes of Health (NIH) [AI037526]; NIH/National Cancer
Institute [RO1CA120954]
FX We would like to thank Richard Baer for the CtIP antibody, Davide
Robbiani for the CtIP shRNA, Junjie Chen and Peter McKinnon for mice,
Susan Sharrow and Larry Granger for flow cytometry, and Jeremy Daniel
and Jaqueline Barlow for comments on the manuscript. M.C.N. is a Howard
Hughes Medical Institute investigator. N.F. is a fellow of the Leukemia
and Lymphoma society. This research was supported in part by National
Institutes of Health (NIH) grant AI037526 to M.C.N., NIH/National Cancer
Institute grant RO1CA120954 to J.M.S., and the Intramural Research
Program of the NIH.
NR 66
TC 546
Z9 557
U1 5
U2 44
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD APR 16
PY 2010
VL 141
IS 2
BP 243
EP 254
DI 10.1016/j.cell.2010.03.012
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 584GF
UT WOS:000276738400015
PM 20362325
ER
PT J
AU Crawford, J
Lamb, E
Wasmuth, J
Grujic, O
Grigg, ME
Boulanger, MJ
AF Crawford, Joanna
Lamb, Erika
Wasmuth, James
Grujic, Ognjen
Grigg, Michael E.
Boulanger, Martin J.
TI Structural and Functional Characterization of SporoSAG A SAG2-RELATED
SURFACE ANTIGEN FROM TOXOPLASMA GONDII
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; SURFACE-ANTIGEN; WATERBORNE TOXOPLASMOSIS;
SRS SUPERFAMILY; DATA-COLLECTION; SWINE FARMS; PROTEIN; OUTBREAK;
HUMANS; CATS
AB Toxoplasma gondii, the etiological agent of toxoplasmosis, utilizes stage-specific expression of antigenically distinct glycosylphosphatidylinositol-tethered surface coat proteins to promote and establish chronic infection. Of the three infective stages of T. gondii, sporozoites are encapsulated in highly infectious oocysts that have been linked to large scale outbreaks of toxoplasmosis. SporoSAG (surface antigen glycoprotein) is the dominant surface coat protein expressed on the surface of sporozoites. Using a bioinformatic approach, we show that SporoSAG clusters with the SAG2 subfamily of the SAG1-related superfamily (SRS) and is non-polymorphic among the 11 haplogroups of T. gondii strains. In contrast to the immunodominant SAG1 protein expressed on tachyzoites, SporoSAG is non-immunogenic during natural infection. We report the 1.60 angstrom resolution crystal structure of SporoSAG solved using cadmium single anomalous dispersion. SporoSAG crystallized as a monomer and displays unique features of the SRS beta-sandwich fold relative to SAG1 and BSR4. Intriguingly, the structural diversity is localized to the upper sheets of the beta-sandwich fold and may have important implications for multimerization and host cell ligand recognition. The structure of SporoSAG also reveals an unexpectedly acidic surface that contrasts with the previously determined SAG1 and BSR4 structures where a basic surface is predicted to play a role in binding negatively charged glycosaminoglycans. Our structural and functional characterization of SporoSAG provides a rationale for the evolutionary divergence of this key SRS family member.
C1 [Lamb, Erika; Grigg, Michael E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Crawford, Joanna; Grujic, Ognjen; Boulanger, Martin J.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada.
[Wasmuth, James] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1L7, Canada.
RP Grigg, ME (reprint author), NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM griggm@niaid.nih.gov; mboulang@uvic.ca
RI Crawford, Joanna /F-9135-2013
OI Crawford, Joanna /0000-0003-0786-6889
FU Canadian Institutes of Health Research (CIHR) [MOP82915]; National
Institutes of Health through the NIAID
FX This work was supported by Research Grant MOP82915 from the Canadian
Institutes of Health Research (CIHR) (to M. J. B.). This work was also
supported by the Intramural Research Program of the National Institutes
of Health (to M. E. G.) through the NIAID.
NR 48
TC 17
Z9 17
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 16
PY 2010
VL 285
IS 16
BP 12063
EP 12070
DI 10.1074/jbc.M109.054866
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 584XI
UT WOS:000276787100035
PM 20164173
ER
PT J
AU Mayers, CM
Wadell, J
McLean, K
Venere, M
Malik, M
Shibata, T
Driggers, PH
Kino, T
Guo, XC
Koide, H
Gorivodsky, M
Grinberg, A
Mukhopadhyay, M
Abu-Asab, M
Westphal, H
Segars, JH
AF Mayers, Chantal M.
Wadell, Jennifer
McLean, Kate
Venere, Monica
Malik, Minnie
Shibata, Takahisa
Driggers, Paul H.
Kino, Tomoshige
Guo, X. Catherine
Koide, Hisashi
Gorivodsky, Marat
Grinberg, Alex
Mukhopadhyay, Mahua
Abu-Asab, Mones
Westphal, Heiner
Segars, James H.
TI Rho Guanine Nucleotide Exchange Factor AKAP13 (BRX) Is Essential for
Cardiac Development in Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SERUM RESPONSE FACTOR; PROTEIN-KINASE-A; MOUSE EMBRYOGENESIS;
GENE-EXPRESSION; ACTIVATION; HEART; LBC; CARDIOMYOCYTES; MORPHOGENESIS;
RAS
AB A fundamental biologic principle is that diverse biologic signals are channeled through shared signaling cascades to regulate development. Large scaffold proteins that bind multiple proteins are capable of coordinating shared signaling pathways to provide specificity to activation of key developmental genes. Although much is known about transcription factors and target genes that regulate cardiomyocyte differentiation, less is known about scaffold proteins that couple signals at the cell surface to differentiation factors in developing heart cells. Here we show that AKAP13( also known as Brx-1, AKAP-Lbc, andproto-Lbc), a unique protein kinase A-anchoring protein (AKAP) guanine nucleotide exchange region belonging to the Dbl family of oncogenes, is essential for cardiac development. Cardiomyocytes of Akap13-null mice had deficient sarcomere formation, and developing hearts were thin-walled and mice died at embryonic day 10.5-11.0. Disruption of Akap13 was accompanied by reduced expression of Mef2C. Consistent with a role of AKAP13 upstream of MEF2C, Akap13 siRNA led to a reduction in Mef2C mRNA, and overexpression of AKAP13 augmented MEF2C-dependent reporter activity. The results suggest that AKAP13 coordinates G alpha(12) and Rho signaling to an essential transcription program in developing cardiomyocytes.
C1 [Driggers, Paul H.; Kino, Tomoshige; Guo, X. Catherine; Koide, Hisashi] NICHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Gorivodsky, Marat; Grinberg, Alex; Mukhopadhyay, Mahua; Westphal, Heiner] NICHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA.
[Abu-Asab, Mones] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Malik, Minnie] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
RP Segars, JH (reprint author), Clin Res Ctr, Bldg 10,Rm 1E-3140,10 Ctr Dr,MSC1109, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU NICHD, National Institutes of Health [ZO1-HD-008737-07-URE]
FX This work was supported, in whole or in part, by the Intramural Research
Program of NICHD, National Institutes of Health, Grant
ZO1-HD-008737-07-URE.
NR 45
TC 28
Z9 30
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 16
PY 2010
VL 285
IS 16
BP 12344
EP 12354
DI 10.1074/jbc.M110.106856
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 584XI
UT WOS:000276787100063
PM 20139090
ER
PT J
AU Pohjoismaki, JLO
Holmes, JB
Wood, SR
Yang, MY
Yasukawa, T
Reyes, A
Bailey, LJ
Cluett, TJ
Goffart, S
Willcox, S
Rigby, RE
Jackson, AP
Spelbrink, JN
Griffith, JD
Crouch, RJ
Jacobs, HT
Holt, IJ
AF Pohjoismaki, Jaakko L. O.
Holmes, J. Bradley
Wood, Stuart R.
Yang, Ming-Yao
Yasukawa, Takehiro
Reyes, Aurelio
Bailey, Laura J.
Cluett, Tricia J.
Goffart, Steffi
Willcox, Smaranda
Rigby, Rachel E.
Jackson, Andrew P.
Spelbrink, Johannes N.
Griffith, Jack D.
Crouch, Robert J.
Jacobs, Howard T.
Holt, Ian J.
TI Mammalian Mitochondrial DNA Replication Intermediates Are Essentially
Duplex but Contain Extensive Tracts of RNA/DNA Hybrid
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
ID MOUSE L CELLS; NUCLEOTIDE-SEQUENCE; LAGGING-STRAND; R-LOOPS; GENOME;
RNA; RIBONUCLEOTIDES; DISPLACEMENT; EXPRESSION; INITIATION
AB We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mitochondrial DNA replication intermediates are essentially duplex throughout their length but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mitochondrial DNA replication involving RNA incorporation throughout the lagging strand. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Holmes, J. Bradley; Wood, Stuart R.; Yang, Ming-Yao; Yasukawa, Takehiro; Reyes, Aurelio; Bailey, Laura J.; Cluett, Tricia J.; Holt, Ian J.] Wellcome Trust Res Labs, MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
[Pohjoismaki, Jaakko L. O.] Univ Tampere, Dept Forens Med, FI-33014 Tampere, Finland.
[Pohjoismaki, Jaakko L. O.; Goffart, Steffi; Spelbrink, Johannes N.; Jacobs, Howard T.] Univ Tampere, Tampere Univ Hosp, FI-33014 Tampere, Finland.
[Pohjoismaki, Jaakko L. O.; Goffart, Steffi; Spelbrink, Johannes N.; Jacobs, Howard T.] Univ Tampere, Inst Med Technol, FI-33014 Tampere, Finland.
[Holmes, J. Bradley; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Willcox, Smaranda; Griffith, Jack D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.
[Rigby, Rachel E.; Jackson, Andrew P.] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
RP Holt, IJ (reprint author), Wellcome Trust Res Labs, MRC Mitochondrial Biol Unit, MRC Bldg,Hills Rd, Cambridge CB2 0XY, England.
EM holt@mrc-mbu.cam.ac.uk
RI Jackson, Andrew/D-3442-2009; Spelbrink, Johannes/L-4661-2015; Goffart,
Steffi/N-3597-2015; Jacobs, Howard/G-2434-2011;
OI Jackson, Andrew/0000-0002-8739-2646; Spelbrink,
Johannes/0000-0002-9756-2602; Goffart, Steffi/0000-0001-8491-1458;
Pohjoismaki, Jaakko/0000-0002-1185-3610; Rigby,
Rachel/0000-0001-5201-9422
FU Medical Research Council; Academy of Finland; Juselius Foundation;
Tampere University Hospital Medical Research Fund; National Institutes
of Health [GM31819]; European Union
FX We thank JiaXiao Shen for technical assistance and Dr. Susana M.
Cerritelli for her critique of the manuscript. The study was funded by
the Medical Research Council, Academy of Finland, Juselius Foundation,
Tampere University Hospital Medical Research Fund, National Institutes
of Health (grant GM31819 and the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development), and the European Union (EUMITOCOMBAT project).
NR 37
TC 52
Z9 52
U1 2
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD APR 16
PY 2010
VL 397
IS 5
BP 1144
EP 1155
DI 10.1016/j.jmb.2010.02.029
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 587IF
UT WOS:000276983300003
PM 20184890
ER
PT J
AU Feero, WG
AF Feero, W. Gregory
TI Examining the Heart of Family Medicine: Family History
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Editorial Material
ID HEALTH
C1 NHGRI, Bethesda, MD 20892 USA.
RP Feero, WG (reprint author), NHGRI, Bethesda, MD 20892 USA.
EM feerow@mail.nih.gov
NR 4
TC 2
Z9 2
U1 0
U2 0
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD APR 15
PY 2010
VL 81
IS 8
BP 961
EP 962
PG 2
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 586PV
UT WOS:000276924500006
PM 20387771
ER
PT J
AU Neta, GI
von Ehrenstein, OS
Goldman, LR
Lum, K
Sundaram, R
Andrews, W
Zhang, J
AF Neta, Gila I.
von Ehrenstein, Ondine S.
Goldman, Lynn R.
Lum, Kirsten
Sundaram, Rajeshwari
Andrews, William
Zhang, Jun
TI Umbilical Cord Serum Cytokine Levels and Risks of
Small-for-Gestational-Age and Preterm Birth
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cytokines; fetal blood, fetal development; infant, small for gestational
age, interferon-gamma; premature birth, tumor necrosis factor-alpha
ID TUMOR-NECROSIS-FACTOR; INTRAUTERINE GROWTH-RETARDATION; MIDTRIMESTER
AMNIOTIC-FLUID; COLONY-STIMULATING FACTOR; FETAL-GROWTH; FACTOR-ALPHA;
PREGNANCY COMPLICATIONS; PROMOTER POLYMORPHISM; PROSPECTIVE COHORT;
NEWBORN-INFANTS
AB While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama Patients were enrolled between 1985 and 1988 For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI). 1.31, 3 06) IFN-gamma was associated with a decreased risk of SGA birth (RR = 0 78, 95% CI. 0 61, 1.01) After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 056, 95% CI 0.31, 1 01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.
C1 [Neta, Gila I.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Neta, Gila I.; Goldman, Lynn R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Goldman, Lynn R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[von Ehrenstein, Ondine S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA.
[Andrews, William] Univ Alabama, Dept Obstet & Gynecol, Sch Med, Birmingham, AL 35294 USA.
RP Neta, GI (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA.
RI Goldman, Lynn/D-5372-2012;
OI Sundaram, Rajeshwari/0000-0002-6918-5002
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported in part by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development
NR 46
TC 27
Z9 33
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 15
PY 2010
VL 171
IS 8
BP 859
EP 867
DI 10.1093/aje/kwq028
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 588NO
UT WOS:000277078300002
PM 20348155
ER
PT J
AU Malhotra, R
Patel, V
Vaque, JP
Gutkind, JS
Rusling, JF
AF Malhotra, Ruchika
Patel, Vyomesh
Vaque, Jose Pedro
Gutkind, J. Silvio
Rusling, James F.
TI Ultrasensitive Electrochemical Immunosensor for Oral Cancer Biomarker
IL-6 Using Carbon Nanotube Forest Electrodes and Multilabel
Amplification
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; PROSTATE-SPECIFIC ANTIGEN; OVARIAN-CANCER;
PROTEIN; HEAD; INTERLEUKIN-6; CHALLENGES; PROTEOMICS; MEDICINE; RECEPTOR
AB Squamous cell carcinomas of head and neck (HNSCC) are associated with immune, inflammatory, and angiogenic responses involving interleukin-6 (IL-6). This article reports an ultrasensitive electrochemical immunosensor for human IL-6 and proof-of-concept studies of IL-6 detection in HNSCC cells. Single wall carbon nanotube (SWNT) forests with attached capture antibodies (Ab(1)) for IL-6 were used in an electrochemical sandwich immunoassay protocol using enzyme label horseradish peroxidase (HRP) to measure very low (<= 30 pg mL(-1)) and elevated levels of IL-6. Two levels of multienzyme labeling were used to measure a broad concentration range of IL-6 in a representative panel of HNSCC cells. Secondary antibodies (Ab(2)) attached to carboxylated multiwall carbon nanotubes with 106 HRP labels per 100 nm gave the highest sensitivity of 19.3 nA mL (pg IL-6)(-1) cm(-2) and the best detection limit (DL) of 0.5 pg mL(-1) (25 fM) for IL-6 in 10 mu L of calf serum. For more concentrated samples, biotinylated Ab(2) bound to streptavidin-HRP to provide 14-16 labels per antigen was used. These immunosensors accurately measured secreted IL-6 in a wide range of HNSCC cells demonstrated by excellent correlations with standard enzyme-linked immunosorbent assays (ELISA), suggesting that SWNT immunosensors combined with multilabel detection have excellent promise for detecting IL-6 in research and clinical applications.
C1 [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA.
[Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA.
[Patel, Vyomesh; Vaque, Jose Pedro; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA.
[Rusling, James F.] Natl Univ Ireland, Galway, Ireland.
RP Rusling, JF (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd, Storrs, CT 06269 USA.
EM james.rusling@uconn.edu
RI Gutkind, J. Silvio/A-1053-2009; Vaque, Jose/H-8413-2015
OI Vaque, Jose/0000-0002-3913-2495
FU National Institutes of Environmental Health Sciences of the National
Institutes of Health [ES013557]; National Institute of Dental and
Craniofacial Research, NIH; Science Foundation Ireland
FX This research was supported by U.S. PHS Grant ES013557 from National
Institutes of Environmental Health Sciences of the National Institutes
of Health and by intramural programs of the National Institute of Dental
and Craniofacial Research, NIH. J.F.R. thanks Science Foundation Ireland
for a Walton Research Fellowship in 2009.
NR 33
TC 181
Z9 187
U1 7
U2 99
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD APR 15
PY 2010
VL 82
IS 8
BP 3118
EP 3123
DI 10.1021/ac902802b
PG 6
WC Chemistry, Analytical
SC Chemistry
GA 581WZ
UT WOS:000276557600005
PM 20192182
ER
PT J
AU Yomtovian, I
Teerakulkittipong, N
Lee, B
Moult, J
Unger, R
AF Yomtovian, Inbal
Teerakulkittipong, Nuttinee
Lee, Byungkook
Moult, John
Unger, Ron
TI Composition bias and the origin of ORFan genes
SO BIOINFORMATICS
LA English
DT Article
ID AMINO-ACID; SEQUENCES; GENOMES
AB Motivation: Intriguingly, sequence analysis of genomes reveals that a large number of genes are unique to each organism. The origin of these genes, termed ORFans, is not known. Here, we explore the origin of ORFan genes by de. ning a simple measure called 'composition bias', based on the deviation of the amino acid composition of a given sequence from the average composition of all proteins of a given genome.
Results: For a set of 47 prokaryotic genomes, we show that the amino acid composition bias of real proteins, random 'proteins' (created by using the nucleotide frequencies of each genome) and 'proteins' translated from intergenic regions are distinct. For ORFans, we observed a correlation between their composition bias and their relative evolutionary age. Recent ORFan proteins have compositions more similar to those of random 'proteins', while the compositions of more ancient ORFan proteins are more similar to those of the set of all proteins of the organism. This observation is consistent with an evolutionary scenario wherein ORFan genes emerged and underwent a large number of random mutations and selection, eventually adapting to the composition preference of their organism over time.
C1 [Unger, Ron] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[Yomtovian, Inbal] Bar Ilan Univ, Dept Comp Sci, IL-52900 Ramat Gan, Israel.
[Teerakulkittipong, Nuttinee; Moult, John] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA.
[Lee, Byungkook] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Unger, R (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
OI Moult, John/0000-0002-3012-2282
FU NIH
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
Partial support from NIH R01GM081511 to J. M., Fulbright Fellowship for
University of Thai Chamber of Commerce, University Staff Development
Program to N.T. and Israel Science Foundation 1339/ 08 to R.U.
NR 18
TC 11
Z9 11
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD APR 15
PY 2010
VL 26
IS 8
BP 996
EP 999
DI 10.1093/bioinformatics/btq093
PG 4
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 584FS
UT WOS:000276737100003
PM 20231229
ER
PT J
AU Biegon, A
Kim, SW
Logan, J
Hooker, JM
Muench, L
Fowler, JS
AF Biegon, Anat
Kim, Sung-Won
Logan, Jean
Hooker, Jacob M.
Muench, Lisa
Fowler, Joanna S.
TI Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron
Emission Tomography Studies in Female Baboons
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Amygdala; CYP19; extragonadal estrogen; imaging; smoking; vorozole
ID CYTOCHROME-P450 AROMATASE; SMOKING; INHIBITORS; COTININE; RATS
AB Background: Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase.
Methods: Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [(11)C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg.
Results: Nicotine administration produced significant, dose-dependent reductions in [(11)C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers.
Conclusions: Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.
C1 [Biegon, Anat; Kim, Sung-Won; Logan, Jean; Hooker, Jacob M.; Muench, Lisa; Fowler, Joanna S.] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Kim, Sung-Won; Muench, Lisa] NIAAA, Bethesda, MD USA.
RP Biegon, A (reprint author), Bldg 490 Med, Upton, NY 11973 USA.
EM biegon@bnl.gov
OI Hooker, Jacob/0000-0002-9394-7708; Logan, Jean/0000-0002-6993-9994
FU Brookhaven National Laboratory [DE-AC02-98CH10886]; National Institutes
of Health [RO1 NS050285, KO5DA020001]
FX This study was carried out with the infrastructure of the Brookhaven
National Laboratory under contract DE-AC02-98CH10886. This work was
supported in pail by National Institutes of Health RO1 NS050285 (AB) and
KO5DA020001 (JSF).
NR 20
TC 14
Z9 16
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2010
VL 67
IS 8
BP 774
EP 777
DI 10.1016/j.biopsych.2010.01.004
PG 4
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 584EE
UT WOS:000276732600012
PM 20188349
ER
PT J
AU Karakurt, A
Ozalp, M
Isik, S
Stables, JP
Dalkara, S
AF Karakurt, Arzu
Ozalp, Meral
Isik, Samil
Stables, James P.
Dalkara, Sevim
TI Synthesis, anticonvulsant and antimicrobial activities of some new
2-acetylnaphthalene derivatives
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE 2-Acetylnaphthalene; (Arylalkyl)imidazole; Antimicrobial activity;
Anticonvulsant activity
ID OXIME ETHER DERIVATIVES; AGENTS; INHIBITORS; ACID; GABA
AB In this study, as a continuation of our research for new (arylalkyl) imidazole anticonvulsant compounds, the design, synthesis and anticonvulsant/antimicrobial activity evaluation of a series of 2-acetylnaphthalene derivatives have been described. Molecular design of the compounds has been based on the modification of nafimidone [1-(2-naphthyl)-2-(imidazol-1-yl)ethanone], which is a representative of the (arylalkyl) imidazole anticonvulsant compounds as well as its active metabolite, nafimidone alcohol (3, 4). In general, these compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings and subjected to some other modifications to evaluate additional structure-activity relationships. The anticonvulsant activity profile of those compounds was determined by maximal electroshock seizure (MES) and subcutaneous metrazol (scM) seizure tests, whereas their neurotoxicity was examined using rotarod test. All the ester derivatives of nafimidone alcohol (5a-h), which were designed as prodrugs, showed anticonvulsant activity against MES-induced seizure model. Four of the most active compounds were chosen for further anticonvulsant evaluations. Quantification of anticonvulsant protection was calculated via the ip route (ED(50) and TD(50)) for the most active candidate (5d). Observed protection in the MES model was 38.46 mg kg (1) and 123.83 mg kg (1) in mice and 20.44 mg kg (1), 56.36 mg kg (1) in rats, respectively. Most of the compounds with imidazole ring also showed antibacterial and/ or antifungal activities to a certain extent in addition to their anticonvulsant activity. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Karakurt, Arzu; Dalkara, Sevim] Hacettepe Univ, Fac Pharm, Dept Pharmaceut Chem, TR-06100 Ankara, Turkey.
[Ozalp, Meral] Hacettepe Univ, Fac Pharm, Pharmaceut Microbiol Dept, TR-06100 Ankara, Turkey.
[Isik, Samil] Ondokuz Mayis Univ, Dept Phys, Fac Art & Sci, TR-55139 Kurupelit, Samsun, Turkey.
[Stables, James P.] Natl Inst Neurol Disorders & Stroke, Anticonvulsant Screening Program, Rockville, MD 20852 USA.
RP Karakurt, A (reprint author), Inonu Univ, Dept Pharmaceut Chem, Fac Pharm, TR-44280 Malatya, Turkey.
EM akarakurt@inonu.edu.tr
FU Hacettepe University [HUBAB 02 02 301 002]
FX This project was supported by Hacettepe University Scientific Research
Fund (HUBAB 02 02 301 002).
NR 31
TC 36
Z9 36
U1 0
U2 15
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 APR 15
PY 2010
VL 18
IS 8
BP 2902
EP 2911
DI 10.1016/j.bmc.2010.03.010
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 581MV
UT WOS:000276528700010
PM 20363141
ER
PT J
AU Etoga, JLG
Ahmed, SK
Patel, S
Bridges, RJ
Thompson, CM
AF Etoga, Jean-Louis G.
Ahmed, S. Kaleem
Patel, Sarjubhai
Bridges, Richard J.
Thompson, Charles M.
TI Conformationally-restricted amino acid analogues bearing a distal
sulfonic acid show selective inhibition of system x(c)(-) over the
vesicular glutamate transporter
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Glutamate; Amino acid analog; Inhibitor; VGLUT; System x(c)(-); Sulfonic
acid
ID SYNAPTIC VESICLES; QUINOLINE-2,4-DICARBOXYLIC ACIDS;
COMPETITIVE-INHIBITION; SUBSTRATE; BRAIN; PHARMACOLOGY; RECEPTORS;
EXCHANGER; VGLUT
AB A panel of amino acid analogs and conformationally-restricted amino acids bearing a sulfonic acid were synthesized and tested for their ability to preferentially inhibit the obligate cysteine-glutamate transporter system x(c)(-) versus the vesicular glutamate transporter (VGLUT). Several promising candidate molecules were identified: R/S-4-[4'-carboxyphenyl]-phenylglycine, a biphenyl substituted analog of 4-carboxyphenylglycine and 2-thiopheneglycine-5-sulfonic acid both of which reduced glutamate uptake at system x(c)(-) by 70-75% while having modest to no effect on glutamate uptake at VGLUT. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Ahmed, S. Kaleem; Patel, Sarjubhai; Bridges, Richard J.; Thompson, Charles M.] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
[Thompson, Charles M.] ATERIS Technol LLC, Missoula, MT 59802 USA.
[Etoga, Jean-Louis G.] Univ Montana, Dept Chem & Biochem, Missoula, MT 59812 USA.
RP Thompson, CM (reprint author), Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
EM charles.thompson@umontana.edu
RI Ahmed, Syed/I-5530-2013
FU NIH [NS38248]; SBIR [R43 ES016392, U44 NS058229, NS30570, NS42077]; Core
Laboratory for Neuromolecular Production [NIH P30-NS055022]; COBRE
Center for Structural and Functional Neuroscience [NIH P20-RR015583]
FX The authors thank J. Gerdes and N. Natale for advice. This research was
supported in part by NIH NS38248 (C. M. T.), SBIR Grants to ATERIS
Technologies LLC (R43 ES016392 U44 NS058229), NS30570 (R. J. B.) and
NS42077 (R. J. B.), as well as by the Core Laboratory for Neuromolecular
Production (NIH P30-NS055022) and the COBRE Center for Structural and
Functional Neuroscience (NIH P20-RR015583).
NR 33
TC 9
Z9 9
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD APR 15
PY 2010
VL 20
IS 8
BP 2680
EP 2683
DI 10.1016/j.bmcl.2009.10.020
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 578KF
UT WOS:000276291500065
PM 20303751
ER
PT J
AU Dunleavy, K
Little, RF
Pittaluga, S
Grant, N
Wayne, AS
Carrasquillo, JA
Steinberg, SM
Yarchoan, R
Jaffe, ES
Wilson, WH
AF Dunleavy, Kieron
Little, Richard F.
Pittaluga, Stefania
Grant, Nicole
Wayne, Alan S.
Carrasquillo, Jorge A.
Steinberg, Seth M.
Yarchoan, Robert
Jaffe, Elaine S.
Wilson, Wyndham H.
TI The role of tumor histogenesis, FDG-PET, and short-course EPOCH with
dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large
B-cell lymphoma
SO BLOOD
LA English
DT Article
ID AIDS-RELATED LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACTIVE ANTIRETROVIRAL
THERAPY; POSITRON-EMISSION-TOMOGRAPHY; ADJUSTED EPOCH; INTENSIVE
CHEMOTHERAPY; TISSUE MICROARRAY; PHASE-II; CONSORTIUM; INFECTION
AB This is a phase 2 study to assess the role of tumor histogenesis (subtype), fluorodeoxyglucose positron emission tomography (FDG-PET), and short-course etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with dose-dense rituximab (SC-EPOCH-RR) in newly diagnosed HIV-associated CD20(+) diffuse large B-cell lymphoma. Patients received a minimum of 3 and a maximum of 6 cycles with 1 cycle beyond stable radiographic and FDG-PET scans. Overall, 79% of patients received 3 cycles. Combination antiretroviral therapy was suspended before and resumed after therapy. Thirty-three enrolled patients had a median age of 42 years (range, 9-61 years), and 76% had a high-intermediate or high age-adjusted international prognostic index. At 5 years median follow-up, progression-free and overall survival were 84% and 68%, respectively. There were no treatment-related deaths or new opportunistic infections during treatment, and patients had sustained CD4 cell count recovery and HIV viral control after treatment. FDG-PET after 2 cycles had an excellent negative but poor positive predictive value. Tumor histogenesis was the only characteristic associated with lymphoma-specific outcome with 95% of germinal center B-cell (GCB) versus 44% of non-GCB diffuse large B-cell lymphoma (DLBCL) progression-free at 5 years. SC-EPOCH-RR is highly effective and less immunosuppressive with shorter duration therapy compared with standard strategies. However, new therapeutic advances are needed for non-GCB DLBCL, which remains the important cause of lymphoma-specific death. This trial was registered at www.clinicaltrials.gov as NCT000019253. (Blood. 2010;115(15):3017-3024)
C1 [Wilson, Wyndham H.] NCI, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA.
[Carrasquillo, Jorge A.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
RP Wilson, WH (reprint author), NCI, Metab Branch, Canc Res Ctr, Bldg 10,Rm 4-N-115, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
RI Carrasquillo, Jorge/E-7120-2010;
OI Jaffe, Elaine/0000-0003-4632-0301; Carrasquillo,
Jorge/0000-0002-8513-5734
NR 39
TC 67
Z9 67
U1 1
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 15
PY 2010
VL 115
IS 15
BP 3017
EP 3024
DI 10.1182/blood-2009-11-253039
PG 8
WC Hematology
SC Hematology
GA 583PC
UT WOS:000276689800007
PM 20130244
ER
PT J
AU Zahn, RC
Rett, MD
Li, M
Tang, HL
Korioth-Schmitz, B
Balachandran, H
White, R
Pryputniewicz, S
Letvin, NL
Kaur, A
Montefiori, DC
Carville, A
Hirsch, VM
Allan, JS
Schmitz, JE
AF Zahn, Roland C.
Rett, Melisa D.
Li, Ming
Tang, Haili
Korioth-Schmitz, Birgit
Balachandran, Harikrishnan
White, Robert
Pryputniewicz, Sarah
Letvin, Norman L.
Kaur, Amitinder
Montefiori, David C.
Carville, Angela
Hirsch, Vanessa M.
Allan, Jonathan S.
Schmitz, Joern E.
TI Suppression of adaptive immune responses during primary SIV infection of
sabaeus African green monkeys delays partial containment of viremia but
does not induce disease
SO BLOOD
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY-RESPONSES;
T-LYMPHOCYTE RESPONSES; RHESUS-MONKEYS; SOOTY MANGABEYS; CELL RESPONSES;
CHIMERIC-VIRUS; NATURAL HOST; MACAQUES; VACCINE
AB One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8- and anti-CD20 lymphocyte-depleting antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before challenge with SIV(sab9315BR). In vivo lymphocyte depletion during primary infection resulted in a brief elevation of viremia but not in disease. Based on the magnitude and timing of SIV-specific CD8(+) T-cell responses in the lymphocyte-depleted animals, CD8(+) T-cell responses appear to contribute to viral containment in natural hosts. We found no evidence for a contribution of humoral immune responses in viral containment. These studies indicate that natural hosts have developed mechanisms in addition to classic adaptive immune responses to cope with this lentiviral infection. Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection. (Blood. 2010;115(15):3070-3078)
C1 [Schmitz, Joern E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Life Sci,Div Viral Pathogenesis, Boston, MA 02215 USA.
[Li, Ming; Tang, Haili; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA.
[White, Robert; Allan, Jonathan S.] SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX USA.
[Pryputniewicz, Sarah; Kaur, Amitinder] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Carville, Angela] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Primate Resources, Southborough, MA 01772 USA.
[Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Schmitz, JE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Life Sci,Div Viral Pathogenesis, E CLS 1037,330 Brookline Ave, Boston, MA 02215 USA.
EM jschmitz@bidmc.harvard.edu
RI Korioth-Schmitz, Birgit/M-7816-2015
OI Korioth-Schmitz, Birgit/0000-0002-5271-9223
FU NIH [RR000168]; NIH New England Primate Research Center [AI43890,
AI30034, AI065335]; NIAID Center for HIV/AIDS Vaccine Immunology
[AI067854]; Harvard Medical School Center for AIDS Research [AI060354];
NIH Nonhuman Primate Reagent Resource [AI040101 and RR016001]
FX This work was supported by the NIH (grants RR000168, New England Primate
Research Center; AI43890, A. K.; AI30034, D. C. M.; AI065335, J.E.S.),
NIAID Center for HIV/AIDS Vaccine Immunology (grant AI067854, J.E.S.,
N.L.L.), and the Harvard Medical School Center for AIDS Research (grant
AI060354). Reagents used in this work were provided by the NIH Nonhuman
Primate Reagent Resource (grants AI040101 and RR016001).
NR 50
TC 22
Z9 23
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 15
PY 2010
VL 115
IS 15
BP 3070
EP 3078
DI 10.1182/blood-2009-10-245225
PG 9
WC Hematology
SC Hematology
GA 583PC
UT WOS:000276689800013
PM 20147699
ER
PT J
AU Paul, TA
Bies, J
Small, D
Wolff, L
AF Paul, Thomas A.
Bies, Juraj
Small, Donald
Wolff, Linda
TI Signatures of polycomb repression and reduced H3K4 trimethylation are
associated with p15INK4b DNA methylation in AML
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; EMBRYONIC STEM-CELLS; CPG ISLAND METHYLATION;
CANCER-CELLS; HUMAN GENOME; KINASE INHIBITOR; INK4A-ARF LOCUS; GENE;
P15; P15(INK4B)
AB DNA hypermethylation of the p15INK4b tumor suppressor gene is commonly observed in acute myeloid leukemia (AML). Repressive histone modifications and their associated binding proteins have been implicated in the regulation of DNA methylation and the transcriptional repression of genes with DNA methylation. We have used high-density chromatin immunoprecipitation-on-chip to determine the histone modifications that normally regulate p15INK4b expression in AML cells and how these marks are altered in cells that have p15INK4b DNA methylation. In AML patient blasts without p15INK4b DNA methylation, a bivalent pattern of active (H3K4me3) and repressive (H3K27me3) modifications exist at the p15INK4b promoter. AML patient blasts with p15INK4b DNA methylation lose H3K4me3 at p15INK4b and become exclusively marked by H3K27me3. H3K27me3, as well as EZH2, extends throughout p14ARF and p16INK4a, indicating that polycomb repression of p15INK4b is a common feature in all AML blasts irrespective of the DNA methylation status of the gene. Reactivation of p15INK4b expression in AML cell lines and patient blasts using 5-aza-2'-deoxycytidine (decitabine) and trichostatin A increased H3K4me3 and maintained H3K27me3 enrichment at p15INK4b. These data indicate that AML cells with p15INK4b DNA methylation have an altered histone methylation pattern compared with unmethylated samples and that these changes are reversible by epigenetic drugs. (Blood. 2010;115(15):3098-3108)
C1 [Paul, Thomas A.; Bies, Juraj; Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Small, Donald] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 4124,37 Convent Dr,MSC 4263, Bethesda, MD 20892 USA.
EM lwolff@helix.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 48
TC 51
Z9 52
U1 1
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 15
PY 2010
VL 115
IS 15
BP 3098
EP 3108
PG 11
WC Hematology
SC Hematology
GA 583PC
UT WOS:000276689800016
PM 20190193
ER
PT J
AU Roos, D
Kuhns, DB
Maddalena, A
Bustamante, J
Kannengiesser, C
de Boer, M
van Leeuwen, K
Koker, MY
Wolach, B
Roesler, J
Malech, HL
Holland, SM
Gallin, JI
Stasia, MJ
AF Roos, Dirk
Kuhns, Douglas B.
Maddalena, Anne
Bustamante, Jacinta
Kannengiesser, Caroline
de Boer, Martin
van Leeuwen, Karin
Koker, M. Yavuz
Wolach, Baruch
Roesler, Joachim
Malech, Harry L.
Holland, Steven M.
Gallin, John I.
Stasia, Marie-Jose
TI Hematologically important mutations: The autosomal recessive forms of
chronic granulomatous disease (second update)
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Chronic granulomatous disease; Mutation; Polymorphism; Autosomal
recessive; NADPH oxidase
ID PHAGOCYTE NADPH OXIDASE; SPLICE-SITE MUTATION; POINT MUTATION; JAPANESE
PATIENTS; LIGHT CHAIN; GENE CAUSES; CYBA; PATIENT; P22-PHOX; FAMILIES
AB Chronic granulomatous Disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is essential in the process of intracellular pathogen killing by phagocytic leukocytes. Four of the five genes involved in CGD are autosomal; these are CYBA, encoding p22-phox, NCF2, encoding p67-phox, NCF1, encoding p47-phox, and NCF4, encoding p40-phox. This article lists all mutations identified in these genes in the autosomal forms of CGD. Moreover, polymorphisms in these genes are also given, which should facilitate the recognition of future disease-causing mutations. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Roos, Dirk; de Boer, Martin; van Leeuwen, Karin] Sanquin Res, NL-1066 CX Amsterdam, Netherlands.
[Roos, Dirk; de Boer, Martin; van Leeuwen, Karin] Univ Amsterdam, Acad Med Ctr, Karl Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands.
[Kuhns, Douglas B.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Maddalena, Anne] GeneDx, Gaithersburg, MD USA.
[Bustamante, Jacinta] INSERM, U550, Lab Human Genet Infect Dis, Paris, France.
[Bustamante, Jacinta] Univ Paris 05, Necker Med Sch, Paris, France.
[Kannengiesser, Caroline] Hop Bichat Claude Bernard, Serv Biochim Hormonale & Genet, F-75877 Paris 18, France.
[Kannengiesser, Caroline] Univ Paris 07, U773, Paris, France.
[Koker, M. Yavuz] Erciyes Univ, Immunol Lab, Kayseri, Turkey.
[Koker, M. Yavuz] Erciyes Univ, Cappadocia Transplant Ctr, Kayseri, Turkey.
[Wolach, Baruch] Meir Med Ctr, Dept Pediat, Kefar Sava, Israel.
[Wolach, Baruch] Meir Med Ctr, Lab Leukocyte Funct, Kefar Sava, Israel.
[Roesler, Joachim] Univ Hosp Carl Gustav Carus, Dept Pediat, Dresden, Germany.
[Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] Natl Inst Clin Infect Dis, Lab Clin Infect Dis, NIH, Bethesda, MD USA.
[Stasia, Marie-Jose] Univ Grenoble 1, CNRS, UMR 5525,Chron Granulomatous Dis Diag & Res Ctr, Univ Hosp Grenoble,Therex TIMC Imag, Grenoble, France.
RP Roos, D (reprint author), Sanquin Res, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands.
EM d.roos@sanquin.nl
RI STASIA, Marie Jose/M-7165-2014; koker, Mustafa Yavuz/A-7296-2012;
OI koker, Mustafa Yavuz/0000-0001-7061-8525; Malech,
Harry/0000-0001-5874-5775
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 61
TC 56
Z9 58
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 1079-9796
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD APR 15
PY 2010
VL 44
IS 4
BP 291
EP 299
DI 10.1016/j.bcmd.2010.01.009
PG 9
WC Hematology
SC Hematology
GA 581RC
UT WOS:000276541000017
PM 20167518
ER
PT J
AU Pourgholami, MH
Cai, ZY
Badar, S
Wangoo, K
Poruchynsky, MS
Morris, DL
AF Pourgholami, Mohammad H.
Cai, Zhao Y.
Badar, Samina
Wangoo, Kiran
Poruchynsky, Marianne S.
Morris, David L.
TI Potent inhibition of tumoral hypoxia-inducible factor 1 alpha by
albendazole
SO BMC CANCER
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; IN-VITRO; DRUG-RESISTANCE; CANCER-THERAPY;
CELL-LINES; NUDE-MICE; ANGIOGENESIS; VEGF; METASTASIS; CARCINOMA
AB Background: Emerging reports suggest resistance, increased tumor invasiveness and metastasis arising from treatment with drugs targeting vascular endothelial growth factor (VEGF). It is believed that increased tumoral hypoxia plays a prominent role in the development of these phenomena. Inhibition of tumoral hypoxia inducible factor (HIF-1 alpha) is thus becoming an increasingly attractive therapeutic target in the treatment of cancer. We hypothesized that the anti-VEGF effect of albendazole (ABZ) could be mediated through inhibition of tumoral HIF-1 alpha.
Method: In vitro, the effects of ABZ on HIF-1 alpha levels in human ovarian cancer cells (OVCAR-3) were investigated using hypoxic chamber or desferrioxamine (DFO) induced-hypoxia. In vivo, the effects of ABZ (150 mg/kg, i.p., single dose) on the tumor levels of HIF-1 alpha and VEGF protein and mRNA were investigated by western blotting, RT-PCR and real time-PCR.
Results: In vitro, ABZ inhibited cellular HIF-1 alpha protein accumulation resulting from placement of cells under hypoxic chamber or exposure to DFO. In vivo, tumors excised from vehicle treated mice showed high levels of both HIF-1 alpha and VEGF. Whereas, tumoral HIF-1 alpha and VEGF protein levels were highly suppressed in ABZ treated mice. Tumoral VEGF-mRNA (but not HIF-1 alpha-mRNA) was also found to be highly suppressed by ABZ.
Conclusion: These results demonstrate for the first time the effects of an acute dose of ABZ in profoundly suppressing both HIF-1 alpha and VEGF within the tumor. This dual inhibition may provide additional value in inhibiting angiogenesis and be at least partially effective in inhibiting tumoral HIF-1 alpha surge, tumor invasiveness and metastasis.
C1 [Pourgholami, Mohammad H.; Cai, Zhao Y.; Badar, Samina; Wangoo, Kiran; Morris, David L.] Univ New S Wales, Canc Res Labs, Dept Surg, St George Hosp, Sydney, NSW 2217, Australia.
[Poruchynsky, Marianne S.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Morris, DL (reprint author), Univ New S Wales, Canc Res Labs, Dept Surg, St George Hosp, Sydney, NSW 2217, Australia.
EM david.morris@unsw.edu.au
FU "Lady Fairfax Foundation" Sydney, NSW, Australia
FX This work was supported in part by a grant-in-aid from the "Lady Fairfax
Foundation" Sydney, NSW, Australia.
NR 40
TC 15
Z9 21
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD APR 15
PY 2010
VL 10
AR 143
DI 10.1186/1471-2407-10-143
PG 7
WC Oncology
SC Oncology
GA 597ZS
UT WOS:000277801800001
PM 20398289
ER
PT J
AU Tzeng, JP
Mayer, D
Richman, AR
Lipkus, I
Han, PK
Valle, CG
Carey, LA
Brewer, NT
AF Tzeng, Janice P.
Mayer, Deborah
Richman, Alice R.
Lipkus, Isaac
Han, Paul K.
Valle, Carmina G.
Carey, Lisa A.
Brewer, Noel T.
TI Women's Experiences With Genomic Testing for Breast Cancer Recurrence
Risk
SO CANCER
LA English
DT Article
DE breast cancer; genomic testing; risk communication; recurrence risk;
decision making; adjuvant therapy
ID DECISION-MAKING; CLINICAL-IMPLICATIONS; PROGNOSTIC SIGNATURE; 21-GENE
ASSAY; FOLLOW-UP; INFORMATION; PERCEPTIONS; SUSCEPTIBILITY; PREFERENCES;
VALIDATION
AB BACKGROUND: Few studies have examined how patients understand and use genomic test results when deciding about treatment. This study examined how women receive and incorporate results of Oncotype DX, a genomic test that offers recurrence risk estimates, into decisions about adjuvant treatment for early stage breast cancer. METHODS: Participants in the cross-sectional study were 77 women with early stage, estrogen receptor-positive breast cancer with 0 to 3 positive lymph nodes who received Oncotype DX between 2004 and 2009. Mailed surveys, supplemented by medical chart review, assessed how women received and understood recurrence risk information based on the test. RESULTS: The most common test results were low (50%, 34 of 68) or intermediate (37%, 25 of 68) breast cancer recurrence risk. Most women accurately recalled their recurrence risk based on the test (71%) and felt they understood much of what they were told about it (67%). Approximately 25% of women recalled experiencing test-related distress. Women's perceived recurrence risk was associated with their actual genomic-based recurrence risks, having had a previous cancer diagnosis, and worry about recurrence. Women with high recurrence risk typically had chemotherapy (78%, 7 of 9), whereas only 2 with a low recurrence risk did (37%, 2 of 30). CONCLUSIONS: This is among the first studies to describe patients' experiences with genomic testing for recurrence risk. Although many women understood discussions about their genomic test results, a third reported not fully understanding these discussions, suggesting a need to aid and improve risk communication and treatment decision making. Cancer 2010;116:1992-2000. (C) 2010 American Cancer Society
C1 [Brewer, Noel T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA.
[Mayer, Deborah] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA.
[Lipkus, Isaac] Duke Univ, Sch Nursing, Durham, NC USA.
[Han, Paul K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Valle, Carmina G.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Carey, Lisa A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
RP Brewer, NT (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, 325A Rosenau Hall CB 7440, Chapel Hill, NC 27599 USA.
EM ntb1@unc.edu
OI Han, Paul/0000-0003-0165-1940
FU American Cancer Society [MSRG-06-259-01-CPPB]
FX Supported entirely by grant MSRG-06-259-01-CPPB from the American Cancer
Society.
NR 39
TC 30
Z9 31
U1 1
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 15
PY 2010
VL 116
IS 8
BP 1992
EP 2000
DI 10.1002/cncr.24990
PG 9
WC Oncology
SC Oncology
GA 582GM
UT WOS:000276584700020
PM 20213682
ER
PT J
AU Karami, S
Boffetta, P
Stewart, P
Rothman, N
Hunting, KL
Dosemeci, M
Berndt, SI
Brennan, P
Chow, WH
Moore, LE
AF Karami, Sara
Boffetta, Paolo
Stewart, Patricia
Rothman, Nathaniel
Hunting, Katherine L.
Dosemeci, Mustafa
Berndt, Sonja I.
Brennan, Paul
Chow, Wong-Ho
Moore, Lee E.
TI Occupational Sunlight Exposure and Risk of Renal Cell Carcinoma
SO CANCER
LA English
DT Article
DE renal cell carcinoma; renal cancer; kidney cancer; vitamin D;
ultraviolet; ultraviolet B; sunlight; occupational exposure;
occupational sunlight exposure
ID RECEPTOR GENE POLYMORPHISMS; SUN PROTECTION BEHAVIORS; LUNG-CANCER RISK;
VITAMIN-D; ULTRAVIOLET-RADIATION; 25-HYDROXYVITAMIN D; UNITED-STATES;
SKIN-CANCER; EUROPE; MORTALITY
AB BACKGROUND: Recent findings indicate that vitamin D obtained from ultraviolet (UV) exposure may reduce the risk of several different cancers. Vitamin D is metabolized to its active form within the kidney, which is the major organ for vitamin D metabolism and activity. Because both the incidence of renal cell carcinoma (RCC) and the prevalence of vitamin D deficiency have increased over the past few decades, in the current study, the authors explored whether occupational UV exposure was associated with RCC risk. METHODS: A hospital-based, case-control study of 1097 patients with RCC (cases) and 1476 controls was conducted in 4 Central and Eastern European countries. Demographic and occupational information was collected to examine the association between occupational UV exposure and RCC risk. RESULTS: A significant reduction (24%-38%) in the risk of RCC was observed with increasing occupational UV exposure among men who participated in the study. No association between UV exposure and RCC risk was observed among women who participated. When the analyses were stratified by latitude as another estimate of sunlight intensity, a stronger reduction (71%-73%) in the risk of RCC was observed between UV exposure and cancer risk among men who resided at the highest latitudes. CONCLUSIONS: The current results suggested that, among men, there is an inverse association between occupational UV exposure and the risk of RCC. Replication studies are warranted to confirm these results. Cancer 2010;116:2001-10. Published 2070 by the American Cancer Society.
C1 [Karami, Sara; Stewart, Patricia; Rothman, Nathaniel; Dosemeci, Mustafa; Berndt, Sonja I.; Chow, Wong-Ho; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hunting, Katherine L.] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA.
[Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM karamis@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010120-12]
NR 45
TC 9
Z9 9
U1 1
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 15
PY 2010
VL 116
IS 8
BP 2001
EP 2010
DI 10.1002/cncr.24939
PG 10
WC Oncology
SC Oncology
GA 582GM
UT WOS:000276584700021
PM 20213683
ER
PT J
AU Reece, KM
Figg, WD
AF Reece, Kelie M.
Figg, William D.
TI A novel regulator (USP10) of p53 Implications for tumor suppression and
therapeutic targeting
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
ID MDM2; CHK2
C1 [Reece, Kelie M.; Figg, William D.] NCI, NIH, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, NIH, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 9
TC 2
Z9 2
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD APR 15
PY 2010
VL 9
IS 8
BP 583
EP 584
DI 10.4161/cbt.9.8.11690
PG 2
WC Oncology
SC Oncology
GA 662SP
UT WOS:000282832600003
PM 20720457
ER
PT J
AU Burns, WR
Zhao, YB
Frankel, TL
Hinrichs, CS
Zheng, ZL
Xu, H
Feldman, SA
Ferrone, S
Rosenberg, SA
Morgan, RA
AF Burns, William R.
Zhao, Yangbing
Frankel, Timothy L.
Hinrichs, Christian S.
Zheng, Zhili
Xu, Hui
Feldman, Steven A.
Ferrone, Soldano
Rosenberg, Steven A.
Morgan, Richard A.
TI A High Molecular Weight Melanoma-Associated Antigen-Specific Chimeric
Antigen Receptor Redirects Lymphocytes to Target Human Melanomas
SO CANCER RESEARCH
LA English
DT Article
ID T-CELL-RECEPTORS; MONOCLONAL-ANTIBODIES; CANCER-IMMUNOTHERAPY;
ANTITUMOR-ACTIVITY; GENE-THERAPY; NEUROBLASTOMA; ACTIVATION; REGRESSION;
DOMAINS; TISSUES
AB Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen-restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3 zeta activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, was non-MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. Cancer Res; 70(8); 3027-33. (C) 2010 AACR.
C1 [Burns, William R.; Frankel, Timothy L.; Hinrichs, Christian S.; Zheng, Zhili; Xu, Hui; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Yangbing] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA.
[Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA.
[Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,CRC 3W5940, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH
FX Grant Support; Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, NIH.
NR 20
TC 40
Z9 42
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2010
VL 70
IS 8
BP 3027
EP 3033
DI 10.1158/0008-5472.CAN-09-2824
PG 7
WC Oncology
SC Oncology
GA 607GC
UT WOS:000278486100006
PM 20395199
ER
PT J
AU Woo, HG
Lee, JH
Yoon, JH
Kim, CY
Lee, HS
Jang, JJ
Yi, NJ
Suh, KS
Lee, KU
Park, ES
Thorgeirsson, SS
Kim, YJ
AF Woo, Hyun Goo
Lee, Jeong-Hoon
Yoon, Jung-Hwan
Kim, Chung Yong
Lee, Hyo-Suk
Jang, Ja June
Yi, Nam-Joon
Suh, Kyung-Suk
Lee, Kuhn Uk
Park, Eun Sung
Thorgeirsson, Snorri S.
Kim, Yoon Jun
TI Identification of a Cholangiocarcinoma-Like Gene Expression Trait in
Hepatocellular Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HEPATIC PROGENITOR CELLS; INTRAHEPATIC
CHOLANGIOCARCINOMA; C-MYC; CLASSIFICATION; DIFFERENTIATION; TARGETS;
ORIGIN; GLIOMA; TUMORS
AB Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapping phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). Similar to CC and CHC, CLHCC showed an aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell-like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that the prognostic value of the CC signatures was independent of the expression of those signatures. In conclusion, we suggest that the acquisition of cholangiocarcinoma-like expression traits plays a critical role in the heterogeneous progression of HCC. Cancer Res; 70(8); 3034-41. (C) 2010 AACR.
C1 [Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Chung Yong; Lee, Hyo-Suk; Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea.
[Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Chung Yong; Lee, Hyo-Suk; Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul 110744, South Korea.
[Jang, Ja June] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110744, South Korea.
[Yi, Nam-Joon; Suh, Kyung-Suk; Lee, Kuhn Uk] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110744, South Korea.
[Woo, Hyun Goo; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Woo, Hyun Goo] Ajou Univ, Sch Med, Dept Physiol, Suwon 441749, South Korea.
[Park, Eun Sung] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77030 USA.
RP Kim, YJ (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28 Yongon Dong, Seoul 110744, South Korea.
EM yoonjun@snu.ac.kr
RI Jang, JaJune/F-6647-2011; Seoul National University,
Pathology/B-6702-2012; Kim, Yoon Jun/J-2746-2012; Yoon, Jung
Hwan/J-5563-2012; Lee, Hyo-Suk/J-5618-2012; Yi, Nam-Joon/J-5574-2012;
Suh, Kyung-Suk/J-5508-2012;
OI Lee, Jeong-Hoon/0000-0002-0315-2080
FU Korea Research Foundation [KRF-2005-041-E00160]; Ministry for Health,
Welfare, and Family Affairs, Republic of Korea [0920280]; Ministry of
Education, Science and Technology [2009-0087452]
FX Grant Support; Korea Research Foundation (grant no.
KRF-2005-041-E00160), a grant from the National R&D Program for Cancer
Control, Ministry for Health, Welfare, and Family Affairs, Republic of
Korea (0920280), and the Basic Research Laboratory program through the
National Research Foundation of Korea funded by the Ministry of
Education, Science and Technology (2009-0087452).
NR 33
TC 66
Z9 67
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2010
VL 70
IS 8
BP 3034
EP 3041
DI 10.1158/0008-5472.CAN-09-2823
PG 8
WC Oncology
SC Oncology
GA 607GC
UT WOS:000278486100007
PM 20395200
ER
PT J
AU Liu, PY
Yang, P
Wu, XF
Vikis, HG
Lu, Y
Wang, Y
Schwartz, AG
Pinney, SM
de Andrade, M
Gazdar, A
Gaba, C
Mandal, D
Lee, J
Kupert, E
Seminara, D
Minna, J
Bailey-Wilson, JE
Spitz, M
Amos, CI
Anderson, MW
You, M
AF Liu, Pengyuan
Yang, Ping
Wu, Xifeng
Vikis, Haris G.
Lu, Yan
Wang, Yian
Schwartz, Ann G.
Pinney, Susan M.
de Andrade, Mariza
Gazdar, Adi
Gaba, Colette
Mandal, Diptasri
Lee, Juwon
Kupert, Elena
Seminara, Daniela
Minna, John
Bailey-Wilson, Joan E.
Spitz, Margaret
Amos, Christopher I.
Anderson, Marshall W.
You, Ming
TI A Second Genetic Variant on Chromosome 15q24-25.1 Associates with Lung
Cancer
SO CANCER RESEARCH
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; SUSCEPTIBILITY LOCUS; MULTIPLE ROLES;
DEPENDENCE; RISK; PROLIFERATION; NITROSAMINES; INHIBITION; APOPTOSIS;
DISEASE
AB A common variant on chromosomal region 15q24-25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24-25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24-25.1 identified three major haplotypes (G_T, A_C, and G_C) and provided stronger evidence for association of 15q24-25.1 with lung cancer (P = 9.72 x 10(-9)). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G_T is neutral; the haplotype A_C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 x 10(-7); odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14-1.35]; whereas the haplotype G_C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 x 10(-7); OR, 0.80; 95% CI, 0.73-0.87). We further showed that these two genetic variants on 15q24-25.1 independently influence lung cancer risk (rs1051730: P = 4.42 x 10(-11); OR, 1.60; 95% CI, 1.46-1.74; rs481134: P = 7.01 x 10(-4); OR, 0.81; 95% CI, 0.72-0.92). The second variant on 15q24-25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer. Cancer Res; 70(8); 3128-35. (C) 2010 AACR.
C1 [You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Yang, Ping; de Andrade, Mariza] Mayo Clin, Rochester, MN USA.
[Wu, Xifeng; Spitz, Margaret; Amos, Christopher I.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Schwartz, Ann G.] Karmanos Canc Inst, Detroit, MI USA.
[Pinney, Susan M.; Lee, Juwon; Kupert, Elena; Anderson, Marshall W.] Univ Cincinnati, Cincinnati, OH USA.
[Gazdar, Adi; Minna, John] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Gaba, Colette] Univ Toledo, Coll Med, Toledo, OH 43606 USA.
[Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Seminara, Daniela] NCI, Bethesda, MD 20892 USA.
[Bailey-Wilson, Joan E.] NHGRI, Baltimore, MD USA.
RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA.
EM youm@wudosis.wustl.edu
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU NIH [U01CA76293, R01CA058554, R01CA093643, R01CA099147, R01CA099187,
R01ES012063, R01ES013340, R03CA77118, R01CA80127, P30ES06096,
P50CA70907, N01HG65404, N01-PC35145, P30CA22453, R01CA63700,
DE-FGB-95ER62060]; Mayo Clinic; Department of Defense; National Cancer
Institute; National Human Genome Research Institute; [P30CA 15083]
FX We thank the Fernald Medical Monitoring Program for sharing their
biospecimens and data with us; the lung cancer families who participated
in this research; Vanderbilt University Microarray Shared Resource,
Washington University Genotyping Core, and Mayo Clinic Genotyping Shared
Resource (supported in part by grant P30CA 15083) for their high-caliber
service; Shaw Levy and Jennifer Baker for their assistance in various
aspects of this work; and Jay Tichelaar and Michael James for their
helpful criticisms and comments on the manuscript.; NIH grants
U01CA76293 (Genetic Epidemiology of Lung Cancer Consortium),
R01CA058554, R01CA093643, R01CA099147, R01CA099187, R01ES012063,
R01ES013340, R03CA77118, R01CA80127, P30ES06096, P50CA70907 (Specialized
Program of Research Excellence), N01HG65404, N01-PC35145, P30CA22453,
R01CA63700, and DE-FGB-95ER62060; Mayo Clinic intramural research funds;
and Department of Defense VITAL grant. This study was supported in part
by NIH, the Intramural Research Programs of the National Cancer
Institute, and the National Human Genome Research Institute.
NR 23
TC 3
Z9 3
U1 1
U2 2
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 APR 15
PY 2010
VL 70
IS 8
BP 3128
EP 3135
DI 10.1158/0008-5472.CAN-09-3583
PG 8
WC Oncology
SC Oncology
GA 607GC
UT WOS:000278486100017
PM 20395203
ER
PT J
AU Schiffman, M
Rodriguez, AC
Chen, Z
Wacholder, S
Herrero, R
Hildesheim, A
Desalle, R
Befano, B
Yu, K
Safaeian, M
Sherman, ME
Morales, J
Guillen, D
Alfaro, M
Hutchinson, M
Solomon, D
Castle, PE
Burk, RD
AF Schiffman, Mark
Rodriguez, Ana Cecilia
Chen, Zigui
Wacholder, Sholom
Herrero, Rolando
Hildesheim, Allan
Desalle, Rob
Befano, Brian
Yu, Kai
Safaeian, Mahboobeh
Sherman, Mark E.
Morales, Jorge
Guillen, Diego
Alfaro, Mario
Hutchinson, Martha
Solomon, Diane
Castle, Philip E.
Burk, Robert D.
TI A Population-Based Prospective Study of Carcinogenic Human
Papillomavirus Variant Lineages, Viral Persistence, and Cervical
Neoplasia
SO CANCER RESEARCH
LA English
DT Article
ID WORLDWIDE GENOMIC DIVERSITY; NATURAL-HISTORY; GENITAL-TRACT; COSTA-RICA;
WOMEN; RISK; INFECTION; CANCER; TYPE-16; POLYMORPHISM
AB Human papillomavirus (HPV) types differ profoundly in cervical carcinogenicity. For the most carcinogenic type HPV16, variant lineages representing further evolutionary divergence also differ in cancer risk. Variants of the remaining 10 to 15 carcinogenic HPV types have not been well studied. In the first prospective, population-based study of HPV variants, we explored whether, on average, the oldest evolutionary branches within each carcinogenic type predicted different risks of >2-year viral persistence and/or precancer and cancer [cervical intraepithelial neoplasia grade 3+ (CIN3+)]. We examined the natural history of HPV variants in the 7-year, 10,049-woman Guanacaste Cohort Study, using a nested case-control design. Infections were assigned to a variant lineage determined by phylogenetic parsimony methods based on URR/E6 sequences. We used the Fisher's combination test to evaluate significance of the risk associations, cumulating evidence across types. Globally, for HPV types including HPV16, the P value was 0.01 for persistence and 0.07 for CIN3+. Excluding HPV16, the P values were 0.04 and 0.37, respectively. For HPV16, non-European viral variants were significantly more likely than European variants to cause persistence [odds ratio (OR), 2.6; P = 0.01] and CIN3+ (OR, 2.4; P = 0.004). HPV35 and HPV51 variant lineages also predicted CIN3+. HPV variants generally differ in risk of persistence. For some HPV types, especially HPV16, variant lineages differ in risk of CIN3+. The findings indicate that continued evolution of HPV types has led to even finer genetic discrimination linked to HPV natural history and cervical cancer risk. Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16's unique carcinogenicity. Cancer Res; 70(8); 3159-69. (C) 2010 AACR.
C1 [Schiffman, Mark; Wacholder, Sholom; Hildesheim, Allan; Yu, Kai; Safaeian, Mahboobeh; Sherman, Mark E.; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Solomon, Diane] NCI, Canc Prevent Div, Rockville, MD 20852 USA.
[Rodriguez, Ana Cecilia; Herrero, Rolando; Morales, Jorge; Guillen, Diego; Alfaro, Mario] Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Chen, Zigui; Burk, Robert D.] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Desalle, Rob] Amer Museum Nat Hist, New York, NY 10024 USA.
[Befano, Brian] Informat Management Serv Inc, Silver Spring, MD USA.
[Hutchinson, Martha] Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA.
RP Schiffman, M (reprint author), NCI, Clin Genet Branch, 6120 Execut Blvd,Room 7012, Rockville, MD 20852 USA.
EM schiffmm@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015; Chen, Zigui/E-8490-2017
OI Hildesheim, Allan/0000-0003-0257-2363;
FU National Cancer Institute, NIH, Department of Health and Human Services
[NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, NO1-CP-506535]; National
Cancer Institute [CA78527]
FX Grant Support; The Guanacaste Project was supported by National Cancer
Institute, NIH, Department of Health and Human Services contracts
NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, and NO1-CP-506535. R. D. Burk
was supported by National Cancer Institute grant CA78527 and used the
facilities available through the Einstein Cancer Research Center and
CFAR.
NR 46
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Z9 106
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2010
VL 70
IS 8
BP 3159
EP 3169
DI 10.1158/0008-5472.CAN-09-4179
PG 11
WC Oncology
SC Oncology
GA 607GC
UT WOS:000278486100021
PM 20354192
ER
PT J
AU Juan, AH
Sartorelli, V
AF Juan, Aster H.
Sartorelli, Vittorio
TI MicroRNA-214 and polycomb group proteins A regulatory circuit
controlling differentiation and cell fate decisions
SO CELL CYCLE
LA English
DT Editorial Material
DE microRNA; miR-214; Ezh2; polycomb group; skeletal muscle; embryonic stem
cells; regulatory circuits
ID SKELETAL-MUSCLE DIFFERENTIATION; NONCODING RNA
C1 [Juan, Aster H.; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD USA.
RP Sartorelli, V (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD USA.
EM sartorev@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041126-10]
NR 9
TC 7
Z9 7
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD APR 15
PY 2010
VL 9
IS 8
BP 1445
EP 1446
DI 10.4161/cc.9.8.11472
PG 2
WC Cell Biology
SC Cell Biology
GA 592SK
UT WOS:000277400100001
PM 20372071
ER
PT J
AU Rudloff, U
Samuels, Y
AF Rudloff, Udo
Samuels, Yardena
TI A growing family Adding mutated Erbb4 as a novel cancer target
SO CELL CYCLE
LA English
DT Article
DE Erbb; personalized medicine; somatic mutation; inhibitor; cancer
ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL
TUMOR; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITORS; FACTOR
RECEPTOR MUTATIONS; SMALL-MOLECULE INHIBITORS; GENE COPY NUMBER; SOMATIC
MUTATIONS; ACQUIRED-RESISTANCE
AB As the upward spiral of novel cancer gene discoveries and novel molecular compounds continues to accelerate, a repetitive theme in molecular drug development remains the lack of activity of initially promising agents when given to patients in clinical trials. It is however invigorating that a few targeted agents directed against a select group of a few 'cancer gene superfamilies' have escaped this all to common fate, and have evolved into novel, clinically meaningful molecular therapy strategies. Targeting dysregulated signaling of the epidermal growth factor family of transmembrane receptors (Erbb family) has encompassed over the last decade an ever increasing role in personalized treatment approaches in an increasing number of human malignancies. Erbbs are receptor tyrosine kinases that are important regulators of several signaling pathways. Two of its family members (Erbb1/EGFR and Erbb2/HER2) have previously been shown to be somatically mutated of human cancers. To determine if this family is somatically mutated in melanoma, its sequences were recently analyzed and one of its members, Erbb4, was found to be somatically mutated in 19% of melanoma cases. Functional analysis of seven of its mutations was shown to increase its catalytic and transformation abilities as well as providing essential survival signals. Similar to other Erbb family members, mutant Erbb4 seems to confer "oncogene addiction" on melanoma cells, making it an attractive therapeutic target. Gaining further understanding into the oncogenic mechanism of Erbb4 may not only help in the development of targeted therapy in melanoma patients but might accelerate the acceptance of a novel taxonomy of cancer which is based on the genomic perturbations in cancer genes and cancer gene families and their response to targeted agents.
C1 [Samuels, Yardena] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Rudloff, Udo] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU Intramural NIH HHS [ZIA HG200337-04, Z01 HG200337-02, ZIA HG200337-05,
Z99 HG999999, Z01 HG200337-01, ZIA HG200337-03]
NR 148
TC 17
Z9 18
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD APR 15
PY 2010
VL 9
IS 8
BP 1487
EP 1503
DI 10.4161/cc.9.8.11239
PG 17
WC Cell Biology
SC Cell Biology
GA 592SK
UT WOS:000277400100019
PM 20404484
ER
PT J
AU Bower, JJ
Zhou, YC
Zhou, T
Simpson, DA
Arlander, SJ
Paules, RS
Cordeiro-Stone, M
Kaufmann, WK
AF Bower, Jacquelyn J.
Zhou, Yingchun
Zhou, Tong
Simpson, Dennis A.
Arlander, Sonnet J.
Paules, Richard S.
Cordeiro-Stone, Marila
Kaufmann, William K.
TI Revised genetic requirements for the decatenation G(2) checkpoint The
role of ATM
SO CELL CYCLE
LA English
DT Article
DE ATM; ATR; CHK1; CHK2; CHEK1; CHEK2; p53; decatenation G(2) checkpoint;
ICRF-193
ID TOPOISOMERASE-II-ALPHA; CELL-CYCLE CHECKPOINT; ONCOGENE-INDUCED
SENESCENCE; HUMAN-DIPLOID FIBROBLASTS; DNA STRAND BREAKS;
IONIZING-RADIATION; MAMMALIAN-CELLS; TYPE-16 E6; DAMAGE; INHIBITION
AB The decatenation G(2) checkpoint is proposed to delay cellular progression from G(2) into mitosis when intertwined daughter chromatids are insufficiently decatenated. Previous studies indicated that the ATM- and Rad3-related (ATR) checkpoint kinase, but not the ataxia telangiectasia-mutated (ATM) kinase, was required for decatenation G(2) checkpoint function. Here, we show that the method used to quantify decatenation G(2) checkpoint function can influence the identification of genetic requirements for the checkpoint. Normal human diploid fibroblast (NHDF) lines responded to the topoisomerase II (topo II) catalytic inhibitor ICRF-193 with a stringent G(2) arrest and a reduction in the mitotic index. While siRNA-mediated depletion of ATR and CHEK1 increased the mitotic index in ICRF-193 treated NHDF lines, depletion of these proteins did not affect the mitotic entry rate, indicating that the decatenation G(2) checkpoint was functional. These results suggest that ATR and CHEK1 are not required for the decatenation G(2) checkpoint, but may influence mitotic exit after inhibition of topo II. A re-evaluation of ataxia telangiectasia (AT) cell lines using the mitotic entry assay indicated that ATM was required for the decatenation G(2) checkpoint. Three NHDF cell lines responded to ICRF-193 with a mean 98% inhibition of the mitotic entry rate. Examination of the mitotic entry rates in AT fibroblasts upon treatment with ICRF-193 revealed a significantly attenuated decatenation G(2) checkpoint response, with a mean 59% inhibition of the mitotic entry rate. In addition, a normal lymphoblastoid line exhibited a 95% inhibition of the mitotic entry rate after incubation with ICRF-193, whereas two AT lymphoblastoid lines displayed only 36% and 20% inhibition of the mitotic entry rate. Stable depletion of ATM in normal human fibroblasts with short hairpin RNA also attenuated decatenation G(2) checkpoint function by an average of 40%. Western immunoblot analysis demonstrated that treatment with ICRF-193 induced ATM autophosphorylation and ATM-dependent phosphorylation of Ser15-p53 and Thr68 in Chk2, but no appreciable phosphorylation of Ser139-H2AX or Ser345-Chk1. The results suggest that inhibition of topo II induces ATM to phosphorylate selected targets that contribute to a G(2) arrest independently of DNA damage.
C1 [Bower, Jacquelyn J.; Zhou, Yingchun; Zhou, Tong; Simpson, Dennis A.; Cordeiro-Stone, Marila; Kaufmann, William K.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
[Bower, Jacquelyn J.; Cordeiro-Stone, Marila; Kaufmann, William K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Cordeiro-Stone, Marila; Kaufmann, William K.] Univ N Carolina, Ctr Environm Hlth & Susceptibil, Chapel Hill, NC 27599 USA.
[Arlander, Sonnet J.; Paules, Richard S.] Natl Inst Environm Hlth Sci, Environm Stress & Canc Grp, Res Triangle Pk, NC USA.
RP Kaufmann, WK (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
EM wkarlk@med.unc.edu
FU PHS [CA81343, ES10126, ES07017]; National Institute of Environmental
Health Sciences, NIH
FX Supported in part by PHS grants CA81343, ES10126, ES07017, and by the
Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH (S.J.A. and R.S.P.).
NR 58
TC 17
Z9 17
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD APR 15
PY 2010
VL 9
IS 8
BP 1617
EP 1628
DI 10.4161/cc.9.8.11470
PG 12
WC Cell Biology
SC Cell Biology
GA 592SK
UT WOS:000277400100034
PM 20372057
ER
PT J
AU Brown, MS
Diallo, OT
Hu, M
Ehsanian, R
Yang, XP
Arun, P
Lu, H
Korman, V
Unger, G
Ahmed, K
Van Waes, C
Chen, Z
AF Brown, Matthew S.
Diallo, Oumou T.
Hu, Michael
Ehsanian, Reza
Yang, Xinping
Arun, Pattatheyil
Lu, Hai
Korman, Vicci
Unger, Gretchen
Ahmed, Khalil
Van Waes, Carter
Chen, Zhong
TI CK2 Modulation of NF-kappa B, TP53, and the Malignant Phenotype in Head
and Neck Cancer by Anti-CK2 Oligonucleotides In vitro or In vivo via
Sub-50-nm Nanocapsules
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROTEIN-KINASE CK2; SQUAMOUS-CELL CARCINOMA; SURVIVAL; THERAPY;
EXPRESSION; APOPTOSIS; ASSOCIATION; ALPHA; GENE; PHOSPHORYLATION
AB Purpose: The aim of this study is to investigate the expression of CK2 subunits and CK2 effects on NF kappa B-mediated and TP53-mediated signal activation and gene expression, the malignant phenotype, and chemosensitivity in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo.
Experimental Design: Protein expression of CK2 subunits was investigated by Western blot and immunohistochemistry. CK2 subunits were knocked down by small interfering RNA, and NF-kappa B activation was examined using DNA binding, Western blot, and luciferase reporter assays. Gene expression was measured by quantitative reverse transcription-PCR. Cell growth, survival, motility, and sensitivity to cisplatin were measured by MTT, flow cytometry, and migration assays. In vivo targeting of CK2 alpha/alpha' in HNSCC xenograft models was achieved using anti-CK2 alpha/alpha' oligodeoxynucleotide encapsulated in sub-50-nm tenfibgen nanocapsules.
Results: CK2 subunit proteins were overexpressed in HNSCC lines and tissues. Knockdown of CK2 subunits differentially inhibited I kappa B alpha degradation, NF-kappa B nuclear localization, phosphorylation, DNA binding, and reporter activity. CK2 subunits modulated gene expression and the malignant phenotype involved in cell cycle and migration, whereas CK2 alpha is critical to promote proliferation, antiapoptosis, and cisplatin resistance in vitro. Furthermore, in vivo delivery of anti-CK2 alpha/alpha' oligodeoxynucleotide nanocapsules significantly suppressed tumor growth in HNSCC xenograft models, in association with modulation of CK2 and NF-kappa B regulated molecules, TP53 family proteins, and induction of apoptosis.
Conclusions: Our study reveals a novel role of CK2 in coregulating NF-kappa B activation, TP53/p63 expression, and downstream gene expression. Downregulation of CK2 in HNSCC models in vitro and in vivo shows antitumor effects as well as sensitization to cisplatin. Clin Cancer Res; 16(8); 2295-307. (C) 2010 AACR.
C1 [Brown, Matthew S.; Diallo, Oumou T.; Hu, Michael; Ehsanian, Reza; Yang, Xinping; Arun, Pattatheyil; Lu, Hai; Van Waes, Carter; Chen, Zhong] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Tumor Biol Sect, Bethesda, MD 20892 USA.
[Korman, Vicci; Unger, Gretchen] GeneSegues Inc, Chaska, MN USA.
[Ahmed, Khalil] Univ Minnesota, Res Serv 151, VA Med Ctr, Minneapolis, MN USA.
[Ahmed, Khalil] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA.
RP Chen, Z (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Tumor Biol Sect, Bldg 10,Room 5D55,10 Ctr Dr,MSC 1419, Bethesda, MD 20892 USA.
EM chenz@nidcd.nih.gov
FU NIH/NIDCD [ZIA-DC-000016, ZIA-DC-000073-02, R43CA-9936601]; VA Merit
Review Funds [UO1-CA 15062]; Clinical Research Training Program; NIH;
Pfizer, Inc.; Howard Hughes Medical Institute-NIH; NIH-Oxford
University/Stanford University School of Medicine
FX NIH/NIDCD intramural research projects ZIA-DC-000016, ZIA-DC-000073-02
(C. Van Waes), and R43CA-9936601 (G. Unger) and VA Merit Review Funds
and UO1-CA 15062 (K. Ahmed).; Research funded by Clinical Research
Training Program, a public-private partnership supported jointly by NIH
and Pfizer, Inc. (M. S. Brown and M. Hu). Howard Hughes Medical
Institute-NIH Research Scholars Program and NIH-Oxford
University/Stanford University School of Medicine, Graduate Partnership
Program (R. Ehsanian).
NR 50
TC 39
Z9 43
U1 0
U2 0
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 APR 15
PY 2010
VL 16
IS 8
BP 2295
EP 2307
DI 10.1158/1078-0432.CCR-09-3200
PG 13
WC Oncology
SC Oncology
GA 608OW
UT WOS:000278595900008
PM 20371694
ER
PT J
AU Kontoyiannis, DP
Marr, KA
Park, BJ
Alexander, BD
Anaissie, EJ
Walsh, TJ
Ito, J
Andes, DR
Baddley, JW
Brown, JM
Brumble, LM
Freifeld, AG
Hadley, S
Herwaldt, LA
Kauffman, CA
Knapp, K
Lyon, GM
Morrison, VA
Papanicolaou, G
Patterson, TF
Perl, TM
Schuster, MG
Walker, R
Wannemuehler, KA
Wingard, JR
Chiller, TM
Pappas, PG
AF Kontoyiannis, Dimitrios P.
Marr, Kieren A.
Park, Benjamin J.
Alexander, Barbara D.
Anaissie, Elias J.
Walsh, Thomas J.
Ito, James
Andes, David R.
Baddley, John W.
Brown, Janice M.
Brumble, Lisa M.
Freifeld, Alison G.
Hadley, Susan
Herwaldt, Loreen A.
Kauffman, Carol A.
Knapp, Katherine
Lyon, G. Marshall
Morrison, Vicki A.
Papanicolaou, Genovefa
Patterson, Thomas F.
Perl, Trish M.
Schuster, Mindy G.
Walker, Randall
Wannemuehler, Kathleen A.
Wingard, John R.
Chiller, Tom M.
Pappas, Peter G.
TI Prospective Surveillance for Invasive Fungal Infections in Hematopoietic
Stem Cell Transplant Recipients, 2001-2006: Overview of the
Transplant-Associated Infection Surveillance Network (TRANSNET) Database
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID RISK-FACTORS; MOLD INFECTIONS; PROPHYLACTIC FLUCONAZOLE;
PROGNOSTIC-FACTORS; ASPERGILLOSIS; EPIDEMIOLOGY; AUTOPSY; OUTCOMES;
BLOOD
AB Background. The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies.
Methods. The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts.
Results. We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT.
Conclusions. In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.
C1 [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Unit 402, Houston, TX 77030 USA.
[Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Univ, Baltimore, MD USA.
[Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA.
[Park, Benjamin J.; Wannemuehler, Kathleen A.; Chiller, Tom M.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA.
[Lyon, G. Marshall] Emory Univ, Med Ctr, Atlanta, GA 30322 USA.
[Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA.
[Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Ito, James] City Hope Hosp, Duarte, CA USA.
[Brown, Janice M.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA.
[Andes, David R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Baddley, John W.; Pappas, Peter G.] Univ Alabama, Birmingham, AL USA.
[Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Freifeld, Alison G.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Walker, Randall] Mayo Clin, Coll Med, Rochester, MN USA.
[Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA.
[Morrison, Vicki A.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA.
[Hadley, Susan] Tufts Med Ctr, Boston, MA USA.
[Herwaldt, Loreen A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Kauffman, Carol A.] Univ Michigan, Ann Arbor Vet Affairs Hlth Care Syst, Ann Arbor, MI 48109 USA.
[Knapp, Katherine] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Papanicolaou, Genovefa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Schuster, Mindy G.] Univ Penn, Philadelphia, PA 19104 USA.
RP Kontoyiannis, DP (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Unit 402, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM dkontoyi@mdanderson.org
OI Papanicolaou, Genovefa/0000-0002-2891-079X
FU Merck; Pfizer; Schereing-Plough; Astellas; Nektar Therapeutics; Enzon;
Centers for Disease Control and Prevention [5U01CI000286-05];
Schering-Plough Research Institute; Enzon Pharmaceuticals
FX D. P. K. has received research support and honoraria from
Schering-Plough, Pfizer, Astellas Pharma, Enzon Pharmaceuticals, and
Merck. P. G. P. has received grant support from Merck, Pfizer,
Schereing-Plough, and Astellas and serves as an adhoc advisor for
Novartis, Basilea, Merck, Pfizer, and Astellas. D. R. A. has received
grant support and serves as an ad hoc advisor for Merck, Pfizer, and
Schering-Plough. T. F. P. has received esearch support and honoraria
from Merck, Pfizer, Schering-Plough, and Nektar Therapeutics and has
served as a consultant for Basilea, Merck, Nektar, and Pfizer. K. A. M.
has received grant support from Merck and Enzon and serves as an ad hoc
advisor and consultant for Astellas, Basilea, Enzon, Merck, Pfizer, and
Schering-Plough. J.I.I. has received honoraria from Astellas, Enzon,
Pfizer, and Schering-Plough. V. A. M. is on the speakers' bureau for
Amgen, Merck, Pfizer, Schering-Plough, and Celgene. J.R.W. has received
honoraria from Pfizer, Astellas, Basilea, and Merck. All other authors:
no conflicts.; Centers for Disease Control and Prevention (grant
5U01CI000286-05) and grants from Merck, Astellas, Pfizer,
Schering-Plough Research Institute, and Enzon Pharmaceuticals.
NR 24
TC 440
Z9 460
U1 4
U2 36
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2010
VL 50
IS 8
BP 1091
EP 1100
DI 10.1086/651263
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 570BF
UT WOS:000275645900003
PM 20218877
ER
PT J
AU Pappas, PG
Alexander, BD
Andes, DR
Hadley, S
Kauffman, CA
Freifeld, A
Anaissie, EJ
Brumble, LM
Herwaldt, L
Ito, J
Kontoyiannis, DP
Lyon, GM
Marr, KA
Morrison, VA
Park, BJ
Patterson, TF
Perl, TM
Oster, RA
Schuster, MG
Walker, R
Walsh, TJ
Wannemuehler, KA
Chiller, TM
AF Pappas, Peter G.
Alexander, Barbara D.
Andes, David R.
Hadley, Susan
Kauffman, Carol A.
Freifeld, Alison
Anaissie, Elias J.
Brumble, Lisa M.
Herwaldt, Loreen
Ito, James
Kontoyiannis, Dimitrios P.
Lyon, G. Marshall
Marr, Kieren A.
Morrison, Vicki A.
Park, Benjamin J.
Patterson, Thomas F.
Perl, Trish M.
Oster, Robert A.
Schuster, Mindy G.
Walker, Randall
Walsh, Thomas J.
Wannemuehler, Kathleen A.
Chiller, Tom M.
TI Invasive Fungal Infections among Organ Transplant Recipients: Results of
the Transplant-Associated Infection Surveillance Network (TRANSNET)
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID SOLID-ORGAN; RISK-FACTORS; AMPHOTERICIN-B; ASPERGILLOSIS; KIDNEY;
PROPHYLAXIS; CANDIDIASIS; VORICONAZOLE; FLUCONAZOLE
AB Background. Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking.
Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts.
Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005.
Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
C1 [Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Med Ctr, Birmingham, AL 35294 USA.
[Oster, Robert A.] Univ Alabama, Dept Med, Div Prevent Med, Med Ctr, Birmingham, AL 35294 USA.
[Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA.
[Andes, David R.] Univ Wisconsin, Madison, WI 53706 USA.
[Hadley, Susan] Tufts Med Ctr, Boston, MA USA.
[Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Freifeld, Alison] Univ Nebraska Med Ctr, Omaha, NE USA.
[Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA.
[Herwaldt, Loreen] Univ Iowa Hosp, Iowa City, IA USA.
[Ito, James] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA.
[Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA USA.
[Park, Benjamin J.; Wannemuehler, Kathleen A.; Chiller, Tom M.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA.
[Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA.
[Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA.
[Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA.
[Walker, Randall] Mayo Clin, Rochester, MN USA.
[Schuster, Mindy G.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA.
RP Pappas, PG (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Med Ctr, 1900 Univ Blvd,229 THT, Birmingham, AL 35294 USA.
EM pappas@uab.edu
FU Merck; Pfizer; Schereing-Plough; Astellas; Nektar Therapeutics; Enzon
FX P. G. P. has received grant support from Merck, Pfizer,
Schereing-Plough, and Astellas and served as an adhoc advisor for
Novartis, Basilea, Merck, Pfizer, and Astellas. D. R. A. has received
grant support and served as an ad hoc advisor for Merck, Pfizer, and
Schering-Plough. T. F. P. has received research support and honoraria
from Merck, Pfizer, Schering-Plough, and Nektar Therapeutics and has
served as a consultant for Basilea, Merck, Nektar, and Pfizer. K. A. M.
has received grant support from Merck and Enzon and served as an ad hoc
advisor and/or consultant for Astellas, Basilea, Enzon, Merck, Pfizer,
and Schering-Plough. J.I.I. has received honoraria from Astellas, Enzon,
Pfizer, and Schering-Plough. VAM is on the speakers' bureau for Amgen,
Merck, Pfizer, Schering-Plough, and Celgene. All other authors: no
conflicts.
NR 40
TC 414
Z9 425
U1 2
U2 29
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2010
VL 50
IS 8
BP 1101
EP 1111
DI 10.1086/651262
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 570BF
UT WOS:000275645900004
PM 20218876
ER
PT J
AU Monzo, K
Dowd, SR
Minden, JS
Sisson, JC
AF Monzo, Kate
Dowd, Susan R.
Minden, Jonathan S.
Sisson, John C.
TI Proteomic analysis reveals CCT is a target of Fragile X mental
retardation protein regulation in Drosophila
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Fragile X syndrome; FMRP; Drosophila; Midblastula transition; Cleavage;
Cellularization
ID MESSENGER-RNAS; BRAIN; GENE; DIFFERENTIATION; TRANSLATION; CHAPERONIN;
DYNAMICS; COMPLEX; FMR1; MICE
AB Fragile X mental retardation protein (FMRP) is an RNA-binding protein that is required for the translational regulation of specific target mRNAs. Loss of FMRP causes Fragile X syndrome (FXS), the most common form of inherited mental retardation in humans. Understanding the basis for FXS has been limited because few in vivo targets of FMRP have been identified and mechanisms for how FMRP regulates physiological targets are unclear. We have previously demonstrated that Drosophila FMRP (dFMRP) is required in early embryos for cleavage furrow formation. In an effort to identify new targets of dFMRP-dependent regulation and new effectors of cleavage furrow formation, we used two-dimensional difference gel electrophoresis and mass spectrometry to identify proteins that are misexpressed in dfmr1 mutant embryos. Of the 28 proteins identified, we have identified three subunits of the Chaperonin containing TCP-1 (CCT) complex as new direct targets of dFMRP-dependent regulation. Furthermore, we found that the septin Peanut, a known effector of cleavage, is a likely conserved substrate of fly CCT and is mislocalized in both cct and in dfmr1 mutant embryos. Based on these results we propose that dFMRP-dependent regulation of CCT subunits is required for cleavage furrow formation and that at least one of its substrates is affected in dfmr1 embryos suggesting that dFMRP-dependent regulation of CCT contributes to the cleavage furrow formation phenotype. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Monzo, Kate; Sisson, John C.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
[Monzo, Kate; Sisson, John C.] Univ Texas Austin, Sect Mol Cell & Dev Biol, Austin, TX 78712 USA.
[Dowd, Susan R.; Minden, Jonathan S.] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
RP Monzo, K (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA.
EM monzokf@mail.nih.gov; minden@cmu.edu
FU NIGMS NIH HHS [R01 GM087562-01]
NR 42
TC 8
Z9 9
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD APR 15
PY 2010
VL 340
IS 2
BP 408
EP 418
DI 10.1016/j.ydbio.2010.01.028
PG 11
WC Developmental Biology
SC Developmental Biology
GA 586VP
UT WOS:000276942600023
PM 20122915
ER
PT J
AU Tripathi, P
Guo, QS
Wang, YQ
Coussens, M
Liapis, H
Jain, S
Kuehn, MR
Capecchi, MR
Chen, F
AF Tripathi, Piyush
Guo, Qiusha
Wang, Yinqiu
Coussens, Matthew
Liapis, Helen
Jain, Sanjay
Kuehn, Michael R.
Capecchi, Mario R.
Chen, Feng
TI Midline signaling regulates kidney positioning but not nephrogenesis
through Shh
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Kidney development; Horseshoe kidney; Notochord; Sonic Hedgehog;
Diphtheria toxin; Ureteric bud; Metanephric mesenchyme; Intermediate
mesoderm; Wolffian duct; Mediolateral positioning
ID INTERMEDIATE MESODERM; URINARY-TRACT; NOTOCHORD; MICE; MORPHOGENESIS;
MESENCHYME; ANOMALIES; MUTATION; STRAIN; CELLS
AB The role of axial structures, especially the notochord, in metanephric kidney development has not been directly examined. Here, we showed that disruption of the notochord and floor plate by diphtheria toxin (DTA)-mediated cell ablation did not disrupt nephrogenesis, but resulted in kidney fusions, resembling horseshoe kidneys in humans. Axial disruptions led to more medially positioned metanephric mesenchyme (MM) in midgestation. However, neither axial disruption nor the ensuing positional shift of the MM affected the formation of nephrons and other structures within the kidney. Response to Shh signaling was greatly reduced in midline cell populations in the mutants. To further ascertain the molecular mechanism underlying these abnormalities, we specifically inactivated Shh in the notochord and floor plate. We found that depleting the axial source of Shh was sufficient to cause kidney fusion, even in the presence of the notochord. These results suggested that the notochord is dispensable for nephrogenesis but required for the correct positioning of the metanephric kidney. Axial Shh signal appears to be critical in conferring the effects of axial structures on kidney positioning along the mediolateral axis. These studies also provide insights into the pathogenesis of horseshoe kidneys and how congenital kidney defects can be caused by signals outside the renal primordia. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Chen, Feng] Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA.
[Liapis, Helen; Jain, Sanjay] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21701 USA.
[Capecchi, Mario R.] Univ Utah, HHMI, Salt Lake City, UT USA.
[Chen, Feng] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
RP Chen, F (reprint author), Washington Univ, Sch Med, Dept Internal Med, Div Renal, Campus Box 8126, St Louis, MO 63110 USA.
EM fchen@dom.wustl.edu
RI wang, yq/F-3244-2012; Kuehn, Michael/A-4573-2014
OI Kuehn, Michael/0000-0002-7703-9160
FU Department of Internal Medicine/Renal Division at Washington University
School of Medicine; NIH [DK81592, DK67386]; Georg M. O'Brien Center for
Kidney Disease Research at Washington University [P30DK079333]
FX We thank Dr. Stephen Bonsib (Louisiana State University Health Sciences
Center) for providing the images of the horseshoe kidneys in humans.
F.C. is supported in part by institutional funds from the Department of
Internal Medicine/Renal Division at Washington University School of
Medicine and NIH grants (DK81592 and DK67386). We also thank the Georg
M. O'Brien Center for Kidney Disease Research at Washington University
(P30DK079333) for core services.
NR 31
TC 13
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD APR 15
PY 2010
VL 340
IS 2
BP 518
EP 527
DI 10.1016/j.ydbio.2010.02.007
PG 10
WC Developmental Biology
SC Developmental Biology
GA 586VP
UT WOS:000276942600033
PM 20152829
ER
PT J
AU Trnovec, T
Sovcikova, E
Pavlovcinova, G
Jakubikova, J
Jusko, TA
Hustak, M
Jureckova, D
Palkovicova, L
Kocan, A
Drobna, B
Lancz, K
Wimmerova, S
AF Trnovec, Tomas
Sovcikova, Eva
Pavlovcinova, Gabriela
Jakubikova, Janka
Jusko, Todd A.
Hustak, Milan
Jureckova, Dana
Palkovicova, L'ubica
Kocan, Anton
Drobna, Beata
Lancz, Kinga
Wimmerova, Sona
TI Serum PCB Concentrations and Cochlear Function in 12-Year-Old Children
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID EVOKED OTOACOUSTIC EMISSIONS; POLYCHLORINATED-BIPHENYLS;
DISTORTION-PRODUCT; HEARING-LOSS; ORGANOCHLORINE PESTICIDES;
DEVELOPMENTAL EXPOSURE; URINARY IODINE; PERINATAL EXPOSURE;
SCHOOL-CHILDREN; THYROID VOLUME
AB Experimental evidence from animals indicates that exposure to polychlorinated biphenyls (PCBs) causes deterioration of the outer hair cells (OHCs) of the cochlea. To test this hypothesis in humans, we measured serum PCB concentrations in 574 12-year-old children residing in three districts in the Slovak Republic using high-resolution gas chromatography with microelectron capture detection. As a marker of cochlear status, we measured transient evoked (TE) and distortion product (DP) otoacoustic emissions (OAEs), and assessed the cross-sectional association between serum PCBs and OAEs. Median total PCB concentrations were 352.8, 150.5, and 134.9 ng/g lipid in Michalovce, Svidnik, and Bratislava, respectively. In multivariate regression models where otoacoustic measures were modeled as a function of log (base 10) PCB concentrations with adjustment for gender, age, and site of examination, dioxin-like PCBs, nondioxin-like PCBs and a PCB grouping targeting upregulation of hepatic uridine 5'-diphospho-glucuronosyl-transferase were significantly associated with lower TEOAE powers at 1000 and 1500 Hz. At 1500 Hz, we observed a strong association with sum of PCBs and DL-PCBs, in the left ear only. The DPOAEs at 1000 Hz were associated with all four PCB groupings. The results of this study show that PCBs may affect the OHCs of the cochlea, a result consistent with findings from animal studies published to date.
C1 [Trnovec, Tomas; Sovcikova, Eva; Palkovicova, L'ubica; Kocan, Anton; Drobna, Beata; Lancz, Kinga; Wimmerova, Sona] Slovak Med Univ, Bratislava 83303, Slovakia.
[Pavlovcinova, Gabriela; Jakubikova, Janka] Comenius Univ, Fac Med, Pediat Otorhinolaryngol Dept, Bratislava 83340, Slovakia.
[Jusko, Todd A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Hustak, Milan] Mil Aviat Hosp, Kosice 04086, Slovakia.
[Jureckova, Dana] Hosp Policlin S Kukura, Michalovce 07101, Slovakia.
RP Trnovec, T (reprint author), Slovak Med Univ, Limbova 12, Bratislava 83303, Slovakia.
EM tomas.trnovec@szu.sk
FU Slovak Research and Development Agency [APVT-21-016804]; Fogarty
International Center National Institutes of Health [R03TW007152];
European Commission [SSPE-CT-2005-044232 ENVIRISK]; National Institutes
of Health, National Institute of Environmental Health Sciences
FX This study was supported by grants from the Slovak Research and
Development Agency (APVT-21-016804), Fogarty International Center
National Institutes of Health (No. R03TW007152) and European Commission
(FP6, SSPE-CT-2005-044232 ENVIRISK) and in part by the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences.
NR 53
TC 27
Z9 27
U1 3
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD APR 15
PY 2010
VL 44
IS 8
BP 2884
EP 2889
DI 10.1021/es901918h
PG 6
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 581WK
UT WOS:000276556000024
PM 20384380
ER
PT J
AU Butchi, NB
Du, M
Peterson, KE
AF Butchi, Niranjan B.
Du, Min
Peterson, Karin E.
TI Interactions Between TLR7 and TLR9 Agonists and Receptors Regulate
Innate Immune Responses by Astrocytes and Microglia
SO GLIA
LA English
DT Article
DE brain; cytokines; costimulation; imiquimod; CpG-ODN
ID GENE-EXPRESSION; RETROVIRAL NEUROPATHOGENESIS; VIRUS-INFECTIONS;
DENDRITIC CELLS; CUTTING EDGE; GLIAL-CELLS; ACTIVATION; MICE; ALPHA;
BRAIN
AB Toll-like receptors 7 (TLR7) and 9 (TLR9) are important mediators of innate immune responses. Both receptors are located in endosomal compartments, recognize nucleic acids, and signal via Myeloid differentiation factor 88 (MyD88). In the current study, we analyzed TLR7 and TLR9 induced activation of astrocytes and microglia, two cell types that contribute to innate immune responses in the CNS. TLR7 and TLR9 agonists induced similar cytokine profiles within each cell type. However, there were notable differences in the cytokine profile between astrocytes and microglia, including the production of the anti-inflammatory cytokine IL-10 and antiapoptotic cytokines G-CSF and IL-9 by microglia but not astrocytes. Costimulation studies demonstrated that the TLR7 agonist, imiquimod, could inhibit TLR9 agonist-induced innate immune responses, in both cell types, in a concentration-dependent manner. Surprisingly, this inhibition was not mediated by TLR7, as deficiency in TLR7 did not alter suppression of the TLR9 agonist-induced responses. The suppression of innate immune responses was also not due to an inhibition of TLR9 agonist uptake. This suggested that imiquimod suppression may be a direct effect, possibly by blocking CpG-ODN binding and/or signaling with TLR9, thus limiting cell activation. An antagonistic relationship was also observed between the two receptors in microglia, with TLR7 deficiency resulting in enhanced cytokine responses to CpG-ODN stimulation. Thus, both TLR7 and its agonist can have inhibitory effects on TLR9-induced cytokine responses in glial cells. (C) 2009 Wiley-Liss, Inc.
C1 [Butchi, Niranjan B.; Du, Min; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU NIH; National Center for Research Resources [IP20RR020159]
FX Grant sponsors: Intramural Research Program of the NIH and National
Center for Research Resources; Grant number: IP20RR020159.
NR 41
TC 47
Z9 51
U1 1
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0894-1491
J9 GLIA
JI Glia
PD APR 15
PY 2010
VL 58
IS 6
BP 650
EP 664
DI 10.1002/glia.20952
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 573UD
UT WOS:000275939500002
PM 19998480
ER
PT J
AU Almeida, MQ
Muchow, M
Boikos, S
Bauer, AJ
Griffin, KJ
Tsang, KM
Cheadle, C
Watkins, T
Wen, F
Starost, MF
Bossis, I
Nesterova, M
Stratakis, CA
AF Almeida, Madson Q.
Muchow, Michael
Boikos, Sosipatros
Bauer, Andrew J.
Griffin, Kurt J.
Tsang, Kit Man
Cheadle, Chris
Watkins, Tonya
Wen, Feng
Starost, Matthew F.
Bossis, Ioannis
Nesterova, Maria
Stratakis, Constantine A.
TI Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the
Trp53(+/-) or Rb1(+/-) backgrounds and chemically induced skin
papillomas by dysregulation of the cell cycle and Wnt signaling
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DAVID BIOINFORMATICS RESOURCES; LARGE GENE LISTS; SUBUNIT TYPE 1A;
CARNEY COMPLEX; REGULATORY SUBUNIT; NEUROFIBROMATOSIS TYPE-1;
ADRENOCORTICAL TUMORS; MICROARRAY DATA; S-PHASE; PROTEIN
AB PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a(+/-) mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a(+/-) mice when bred within the Rb1(+/-) or Trp53(+/-) backgrounds, or treated with a two-step skin carcinogenesis protocol. Prkar1a(+/-) Trp53(+/-) mice developed more sarcomas than Trp53(+/-) mice (P < 0.05) and Prkar1a(+/-) Rb1(+/-) mice grew more ( and larger) pituitary and thyroid tumors than Rb1(+/-) mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Prkar1a(+/-) mice also developed more papillomas than wild-type animals. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling, along with cell cycle abnormalities; all changes were confirmed by qRT-PCR array and immunohistochemistry. siRNA down-regulation of Ctnnb1, E2f1 or Cdk4 inhibited proliferation of human adrenal cells bearing a PRKAR1A-inactivating mutation and Prkar1a(+/-) mouse embryonic fibroblasts and arrested both cell lines at the G0/G1 phase of the cell cycle. In conclusion, Prkar1a haploinsufficiency is a relatively weak tumorigenic signal that can act synergistically with other tumor suppressor gene defects or chemicals to induce tumors, mostly through Wnt-signaling activation and cell cycle dysregulation, consistent with studies in human neoplasms carrying PRKAR1A defects.
C1 [Almeida, Madson Q.; Muchow, Michael; Boikos, Sosipatros; Bauer, Andrew J.; Griffin, Kurt J.; Tsang, Kit Man; Wen, Feng; Bossis, Ioannis; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
[Cheadle, Chris; Watkins, Tonya] Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD 21224 USA.
RP Almeida, MQ (reprint author), NICHHD, Endocrinol Sect, Dev Endocrinol Branch, NIH,CRC, Bldg 10,Room 1-3216,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM almeidamd@mail.nih.gov
FU US National Institutes of Health; Eunice Kennedy Shriver National
Institute of Child Health and Human Development intramural project
[Z01-HD-000642-04]
FX This work was supported by US National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
intramural project Z01-HD-000642-04 ( to C. A. S.).
NR 57
TC 31
Z9 31
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 15
PY 2010
VL 19
IS 8
BP 1387
EP 1398
DI 10.1093/hmg/ddq014
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581SE
UT WOS:000276544000001
PM 20080939
ER
PT J
AU Strong, CD
Conlan, S
Deming, CB
Cheng, J
Sears, KE
Segre, JA
AF Strong, Cristina de Guzman
Conlan, Sean
Deming, Clayton B.
Cheng, Jun
Sears, Karen E.
Segre, Julia A.
TI A milieu of regulatory elements in the epidermal differentiation complex
syntenic block: implications for atopic dermatitis and psoriasis
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORNIFIED ENVELOPE; ICHTHYOSIS VULGARIS; NONCODING SEQUENCES; BARRIER
FORMATION; GENE; FILAGGRIN; GENOME; SKIN; MUTATIONS; INSIGHTS
AB Two common inflammatory skin disorders with impaired barrier, atopic dermatitis (AD) and psoriasis, share distinct genetic linkage to the Epidermal Differentiation Complex (EDC) locus on 1q21. The EDC is comprised of tandemly arrayed gene families encoding proteins involved in skin cell differentiation. Discovery of semidominant mutations in filaggrin (FLG) associated with AD and a copy number variation within the LCE genes associated with psoriasis provide compelling evidence for the role of EDC genes in the pathogenesis of these diseases. To date, little is known about the potentially complex regulatory landscape within the EDC. Here, we report a computational approach to identify conserved non-coding elements (CNEs) in the EDC queried for regulatory function. Coordinate expression of EDC genes during mouse embryonic skin development and a striking degree of synteny and linearity in the EDC locus across a wide range of mammalian (placental and marsupial) genomes suggests an evolutionary conserved regulatory milieu in the EDC. CNEs identified by comparative genomics exhibit dynamic regulatory activity (enhancer or repressor) in differentiating or proliferating conditions. We further demonstrate epidermal-specific, developmental in vivo enhancer activities (DNasel and transgenic mouse assays) in CNEs, including one within the psoriasis-associated deletion, LCE3C_LCE3B-del. Together, our multidisciplinary study features a network of regulatory elements coordinating developmental EDC gene expression as an unexplored resource for genetic variants in skin diseases.
C1 [Strong, Cristina de Guzman; Conlan, Sean; Deming, Clayton B.; Cheng, Jun; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Sears, Karen E.] Univ Illinois, Dept Anim Biol, Urbana, IL 61801 USA.
RP Segre, JA (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM jsegre@nhgri.nih.gov
RI Conlan, Sean/B-4401-2008
OI Conlan, Sean/0000-0001-6848-3465
FU National Human Genome Research Institute Intramural Research Program;
National Institute of Health [K99AR055948]
FX This work was supported by the National Human Genome Research Institute
Intramural Research Program and the National Institute of Health
K99AR055948 to C. G. S.
NR 38
TC 28
Z9 29
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 15
PY 2010
VL 19
IS 8
BP 1453
EP 1460
DI 10.1093/hmg/ddq019
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 581SE
UT WOS:000276544000006
ER
PT J
AU Cookson, MR
Bandmann, O
AF Cookson, Mark R.
Bandmann, Oliver
TI Parkinson's disease: insights from pathways
SO HUMAN MOLECULAR GENETICS
LA English
DT Review
ID ALPHA-SYNUCLEIN GENE; CYSTEINE-SULFINIC ACID; MITOCHONDRIAL-FUNCTION;
DOPAMINERGIC-NEURONS; PROTEIN DJ-1; CAENORHABDITIS-ELEGANS; OXIDATIVE
STRESS; MONOGENIC FORMS; PINK1; LRRK2
AB Parkinson's disease (PD) typically presents in sporadic fashion, but the identification of disease-causing mutations in monogenically inherited PD genes has provided crucial insight into the pathogenesis of this disorder. Mutations in autosomal recessively inherited genes, namely parkin, PINK1 and DJ-1, typically lead to early onset parkinsonism. At least two of these genes (PINK1 and parkin) appear to work in the same pathway related to maintenance of mitochondrial functional integrity under conditions of oxidative stress. Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) and alpha-synuclein cause late onset PD, generally with Lewy bodies that are characteristic of sporadic PD and there is evidence that these two genes are also in a common pathway. There is also growing evidence from recently undertaken genome-wide association studies that naturally occurring sequence variants in alpha-synuclein and LRRK2, but also Tau, also confer an increased risk for late onset, sporadic PD. Collectively, these results highlight how understanding pathways for inherited PD are starting to impact ideas about the pathogenesis, some of which may also be relevant to the commoner sporadic disease.
C1 [Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bandmann, Oliver] Univ Sheffield, Dept Neurosci, Acad Neurol Unit, E Floor Med Sch, Sheffield S10 2RX, S Yorkshire, England.
RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU NIH; National Institute on Aging; Parkinson's Disease Society (UK)
[G-0715, G-0901]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. Financial support from the
Parkinson's Disease Society (UK) to O.B. is gratefully acknowledged
(G-0715, G-0901).
NR 82
TC 102
Z9 105
U1 1
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 15
PY 2010
VL 19
SI 1
BP R21
EP R27
DI 10.1093/hmg/ddq167
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 613TU
UT WOS:000279004800004
PM 20421364
ER
PT J
AU Freedman, DM
Rajaraman, P
Fuhrman, B
Hoffbeck, R
Alexander, BH
AF Freedman, D. Michal
Rajaraman, Preetha
Fuhrman, Barbara
Hoffbeck, Richard
Alexander, Bruce H.
TI Sunlight, hormone replacement status and colorectal cancer risk in
postmenopausal women
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE vitamin D; colorectal cancer; postmenopausal women; hormone replacement;
ultraviolet radiation
ID VITAMIN-D SUPPLEMENTATION; D METABOLITES; COLON CANCER; ESTROGEN;
CALCIUM; HEALTH; MORTALITY; THERAPY; 25-HYDROXYVITAMIN-D; OSTEOPOROSIS
AB A reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross-sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radio logic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest teak = 0.40; 95% CI 017, 0.93; p for trend = 0.04. Non-significant lower risks were also associated with higher levels of outdoor time (>3.5 hr/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.
C1 [Freedman, D. Michal; Rajaraman, Preetha; Fuhrman, Barbara] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Hoffbeck, Richard; Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS Room 7036,6120 Exec Blvd, Bethesda, MD 20892 USA.
EM mf101e@nih.gov
OI Fuhrman, Barbara/0000-0002-1777-9888
FU National Institutes of Health; National Cancer Institute; U.S. Public
Health Service of the Department of Health and Human Services
FX Grant sponsors: Intramural Research Program of the National Institutes
of Health, National Cancer Institute, the U.S. Public Health Service of
the Department of Health and Human Services
NR 22
TC 12
Z9 12
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD APR 15
PY 2010
VL 126
IS 8
BP 1997
EP 2001
DI 10.1002/ijc.24903
PG 5
WC Oncology
SC Oncology
GA 574EW
UT WOS:000275972500023
PM 19795420
ER
PT J
AU Coy, SL
Krylov, EV
Schneider, BB
Covey, TR
Brenner, DJ
Tyburski, JB
Patterson, AD
Krausz, KW
Fornace, AJ
Nazarova, EG
AF Coy, Stephen L.
Krylov, Evgeny V.
Schneider, Bradley B.
Covey, Thomas R.
Brenner, David J.
Tyburski, John B.
Patterson, Andrew D.
Krausz, Kris W.
Fornace, Albert J.
Nazarova, Erkinjon G.
TI Detection of radiation-exposure biomarkers by differential mobility
prefiltered mass spectrometry (DMS-MS)
SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE Metabolomic; Radiation exposure; DMS; Ion mobility; Electrospray
ID ELECTROSPRAY-IONIZATION; N-HEXANOYLGLYCINE; URINE; METABOLOMICS;
SEPARATION; SYSTEM; GAS; IDENTIFICATION; MICE
AB Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH/NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry-mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Coy, Stephen L.; Krylov, Evgeny V.; Nazarova, Erkinjon G.] Sionex Corp, Bedford, MA 01730 USA.
[Schneider, Bradley B.; Covey, Thomas R.] AB SCIEX, Concord, ON L4K 4V8, Canada.
[Brenner, David J.] Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA.
[Tyburski, John B.; Patterson, Andrew D.; Krausz, Kris W.] NCI, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA.
[Fornace, Albert J.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Fornace, Albert J.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
RP Coy, SL (reprint author), Sionex Corp, 8-A Preston Ct, Bedford, MA 01730 USA.
EM scoy@sionex.com
RI Fornace, Albert/A-7407-2008; Patterson, Andrew/G-3852-2012
OI Fornace, Albert/0000-0001-9695-085X; Patterson,
Andrew/0000-0003-2073-0070
FU Columbia University Center; NIH/NIAID [U19 A1067773-02]
FX This work was supported by the Columbia University Center for Medical
Countermeasures against Radiation (Principal Investigator Prof. David
Brenner), and funded by NIH/NIAID grant U19 A1067773-02. We would
especially like to thank Jeffrey R. Idle for support of Sionex
participation in this project and for his contribution to the
identification of the biomarkers described in Refs. [1-4].
NR 30
TC 30
Z9 30
U1 2
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1387-3806
J9 INT J MASS SPECTROM
JI Int. J. Mass Spectrom.
PD APR 15
PY 2010
VL 291
IS 3
BP 108
EP 117
DI 10.1016/j.ijms.2010.01.013
PG 10
WC Physics, Atomic, Molecular & Chemical; Spectroscopy
SC Physics; Spectroscopy
GA 580DY
UT WOS:000276428400002
PM 20305793
ER
PT J
AU Kozmin, SG
Wang, J
Schaaper, RM
AF Kozmin, Stanislav G.
Wang, Jian
Schaaper, Roel M.
TI Role for CysJ Flavin Reductase in Molybdenum Cofactor-Dependent
Resistance of Escherichia coli to 6-N-Hydroxylaminopurine
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID HYDROXYLATED BASE ANALOGS; SALMONELLA-TYPHIMURIUM; ENZYME; BIOSYNTHESIS;
CONSTRUCTION; COLLECTION; PROTEINS; MUTANTS; STRAINS; BIOLOGY
AB We have previously described a novel Escherichia coli detoxification system for the removal of toxic and mutagenic N-hydroxylated nucleobases and related compounds that requires the molybdenum cofactor. Two subpathways (ycbX and yiiM) were identified, each employing a novel molybdo activity capable of inactivating N-hydroxylated compounds by reduction to the corresponding amine. In the present study, we identify the cysJ gene product as one additional component of this system. While the CysJ protein has been identified as the NADPH: flavin oxidoreductase component of the CysJI sulfite reductase complex (CysJ(8)I(4)), we show that the role of CysJ in base analog detoxification is unique and independent of CysI and sulfite reductase. We further show that CysJ functions as a specific partner of the YcbX molybdoenzyme. We postulate that the function of CysJ in this pathway is to provide, via its NADPH: flavin reductase activity, the reducing equivalents needed for the detoxification reaction at the YcbX molybdocenter. In support of the proposed interaction of the CysJ and YcbX proteins, we show that an apparent CysJ-YcbX "hybrid" protein from two Vibrio species is capable of compensating for a double cysJ ycbX defect in E. coli.
C1 [Kozmin, Stanislav G.; Wang, Jian; Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, MD E3-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM schaaper@niehs.nih.gov
RI Kozmin, Stanislav/J-6849-2012
OI Kozmin, Stanislav/0000-0002-4128-4447
FU NIH [Z01 ES050170]; National Institute of Environmental Health Sciences
FX We thank Matthew Longley and Giang Nguyen of the NIEHS for their
critical reading of the manuscript for this paper.; This research was
supported by funds allocated to project number Z01 ES050170 of the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences.
NR 34
TC 13
Z9 14
U1 1
U2 3
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 APR 15
PY 2010
VL 192
IS 8
BP 2026
EP 2033
DI 10.1128/JB.01438-09
PG 8
WC Microbiology
SC Microbiology
GA 575EB
UT WOS:000276048300002
PM 20118259
ER
PT J
AU Sharma, P
Murillas, R
Zhang, HF
Kuehn, MR
AF Sharma, Prashant
Murillas, Rodolfo
Zhang, Huafeng
Kuehn, Michael R.
TI N4BP1 is a newly identified nucleolar protein that undergoes
SUMO-regulated polyubiquitylation and proteasomal turnover at
promyelocytic leukemia nuclear bodies
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE N4BP1; PML nuclear bodies; SUMO; Nucleolus; Ubiquitin
ID BODY FORMATION; INTRACELLULAR-LOCALIZATION; SUBNUCLEAR LOCALIZATION;
CELL-NUCLEUS; PML PROTEIN; UBIQUITIN; DEGRADATION; INHIBITION; TUMOR;
DAXX
AB A number of proteins can be conjugated with both ubiquitin and the small ubiquitin-related modifier (SUMO), with crosstalk between these two post-translational modifications serving to regulate protein function and stability. We previously identified N4BP1 as a substrate for monoubiquitylation by the E3 ubiquitin ligase Nedd4. Here, we describe Nedd4-mediated polyubiquitylation and proteasomal degradation of N4BP1. In addition, we show that N4BP1 can be conjugated with SUMO1 and that this abrogates N4BP1 ubiquitylation. Consistent with this, endogenous N4BP1 is stabilized in primary embryonic fibroblasts from mutants of the desumoylating enzyme SENP1, which show increased steady-state sumoylation levels. We have localized endogenous N4BP1 predominantly to the nucleolus in primary cells. However, a small fraction is found at promyelocytic leukemia (PML) nuclear bodies (NBs). In cells deficient for SENP1 or in wild-type cells treated with the proteasome inhibitor MG132, there is considerable accumulation of N4BP1 at PML NBs. These findings suggest a dynamic interaction between subnuclear compartments, and a role for post-translational modification by ubiquitin and SUMO in the regulation of nucleolar protein turnover.
C1 [Sharma, Prashant; Zhang, Huafeng; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NCI Frederick, Frederick, MD 21702 USA.
[Murillas, Rodolfo] CIBERER U714, Ctr Invest Energet Medioambientales & Tecnol, Epithelial Biomed Div, Madrid, Spain.
RP Kuehn, MR (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NCI Frederick, Frederick, MD 21702 USA.
EM mkuehn@mail.nih.gov
RI Kuehn, Michael/A-4573-2014; Zhang, Huafeng/A-7188-2012
OI Kuehn, Michael/0000-0002-7703-9160;
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Margaret Lualdi for expert technical assistance, Mary Dasso and
Deborah Morrison for antibodies and reagents, Stephen Lockett for
assistance with imaging, and Oyvind Dahle, Alessandra Mazzoni and Allan
Weissman for critically reading the manuscript. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services and nor does
mention of trade names, commercial products or organizations imply
endorsement by the US Government. Deposited in PMC for release after 12
months.
NR 56
TC 12
Z9 13
U1 0
U2 2
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 APR 15
PY 2010
VL 123
IS 8
BP 1227
EP 1234
DI 10.1242/jcs.060160
PG 8
WC Cell Biology
SC Cell Biology
GA 582AU
UT WOS:000276568200006
PM 20233849
ER
PT J
AU Tsai-Morris, CH
Sheng, Y
Gutti, R
Li, J
Pickel, J
Dufau, ML
AF Tsai-Morris, Chon-Hwa
Sheng, Yi
Gutti, Ravi
Li, Jie
Pickel, James
Dufau, Maria L.
TI Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) Gene:
Cell-Specific Expression and Transcriptional Regulation by Androgen in
Transgenic Mouse Testis
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE DEAD-BOX RNA HELICASE; GRTH/DDX25; ANDROGEN REGULATION; LEYDIG CELLS;
TRANSGENIC MICE; TESTIS
ID PROSTATE-CANCER; RECEPTOR; SPERMATOGENESIS; TRANSLATION; MICE
AB Gonadotropin-regulated testicular RNA helicase is a multifunctional enzyme present in both Leydig and germ cells that is essential for the progress of spermatogenesis. GRTH gene expression is transcriptionally upregulated by human chorionic gonadotropin (hCG) via second messenger (cAMP) and androgen in Leydig cells. The regulatory region(s) in the GRTH gene that is/are required for its cell-specific expression in the testis and hCG/androgen dependent expression were investigated in transgenic mice carrying sequential deletions of 5' flanking sequences of the GRTH gene. GFP-reporter gene expression directed by the GRTH 5' flanking sequences extending to -3.6 kb was specifically located in Leydig cells and the 205 bp minimal promoter domain was sufficient for this cell-specific expression. The 1 kb (5' to the ATG codon) transgene-directed expression was markedly increased by in vivo hCG treatment. Administration of the androgen receptor inhibitor Flutamide blocked the basal and hCG stimulated GFP expression in Leydig cells. We conclude that the expression of GRTH in testicular cells is differentially regulated by its 5' flanking sequence and that the 1 kb fragment of GRTH gene contains sequences for androgen regulation of its expression in Leydig cells. J. Cell. Biochem. 109: 1142-1147, 2010. (C) 2010 Wiley-Liss, Inc,
C1 [Tsai-Morris, Chon-Hwa; Sheng, Yi; Gutti, Ravi; Li, Jie; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Pickel, James] NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA.
RP Tsai-Morris, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bldg 49,Rm 6B-03, Bethesda, MD 20892 USA.
EM morrisch@mail.nih.gov
OI Gutti, Ravi/0000-0002-0912-5796
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Grant sponsor: NIH Intramural Research Program (Eunice Kennedy Shriver
National Institute of Child Health and Human Development).
NR 14
TC 9
Z9 10
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD APR 15
PY 2010
VL 109
IS 6
BP 1142
EP 1147
DI 10.1002/jcb.22493
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 587AI
UT WOS:000276958200010
PM 20108248
ER
PT J
AU Ghysels, A
Van Speybroeck, V
Pauwels, E
Catak, S
Brooks, BR
Van Neck, D
Waroquier, M
AF Ghysels, An
Van Speybroeck, Veronique
Pauwels, Ewald
Catak, Saron
Brooks, Bernard R.
Van Neck, Dimitri
Waroquier, Michel
TI Comparative Study of Various Normal Mode Analysis Techniques Based on
Partial Hessians
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Article
DE Hessian; partial Hessian; NMA, normal modes; vibrational modes; mobile
block Hessian; MBH; vibrational subsystem analysis; VSA; PHVA; RTB;
partial optimization; LAO binding protein; cinchona
ID ORNITHINE-BINDING PROTEIN; FREQUENCY NORMAL-MODES; AB-INITIO; CLUSTER
CALCULATIONS; ASYMMETRIC DIHYDROXYLATION; VIBRATIONAL ANALYSIS;
BIOLOGICAL-SYSTEMS; METHOXY ADSORPTION; FERMI RESONANCES;
SINGLE-PARAMETER
AB Standard normal mode analysis becomes problematic for complex molecular systems, as a result of both the high computational cost and the excessive amount of information when the full Hessian matrix is used. Several partial Hessian methods have been proposed in the literature, yielding approximate normal modes. These methods aim at reducing the computational load and/or calculating only the relevant normal modes of interest in a specific application. Each method has its own (dis)advantages and application field but guidelines for the most Suitable choice are lacking We have investigated several partial Hessian methods. including the Partial Hessian Vibrational Analysis (PHVA), the Mobile Block Hessian (MBH), and the Vibrational Subsystem Analysis (VSA). In this article. we focus on the benefits and drawbacks of these methods, in terms of the reproduction of localized Modes, collective modes. and the performance in partially optimized structures. We find that the PHVA is suitable for describing localized modes, that the MBH not only reproduces localized and global modes but also serves as an analysis too] of the spectrum, and that the VSA is mostly useful for the reproduction of the low frequency spectrum. These guidelines are illustrated with the reproduction of the localized amine-stretch, the spectrum of quinine and a bis-cinchona derivative. and the low frequency modes of the LAO binding protein. (C) 2009 Wiley Periodicals, Inc. J Comput Chem 31: 994-1007, 2010
C1 [Ghysels, An; Van Speybroeck, Veronique; Pauwels, Ewald; Catak, Saron; Van Neck, Dimitri; Waroquier, Michel] Univ Ghent, Ctr Mol Modeling, B-9000 Ghent, Belgium.
[Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Ghysels, A (reprint author), Univ Ghent, Ctr Mol Modeling, Proeftuinstr 86, B-9000 Ghent, Belgium.
EM an.ghysels@ugent.be
RI Catak, Saron/F-4438-2014; Ghysels, An/M-9095-2015
OI Catak, Saron/0000-0002-4396-8375;
FU Ghent Universitv (BOF),; Interuniversity Attraction Poles (IAP)
FX Contract/grant sponsors: Fund for Scientific Research-Flanders (FWO).
Research board of Ghent Universitv (BOF), Belgian program on
Interuniversity Attraction Poles (IAP).
NR 53
TC 33
Z9 34
U1 4
U2 27
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0192-8651
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD APR 15
PY 2010
VL 31
IS 5
BP 994
EP 1007
DI 10.1002/jcc.21386
PG 14
WC Chemistry, Multidisciplinary
SC Chemistry
GA 568LF
UT WOS:000275523100010
PM 19813181
ER
PT J
AU Hensley, SE
Zanker, D
Dolan, BP
David, A
Hickman, HD
Embry, AC
Skon, CN
Grebe, KM
Griffin, TA
Chen, WS
Bennink, JR
Yewdell, JW
AF Hensley, Scott E.
Zanker, Damien
Dolan, Brian P.
David, Alexandre
Hickman, Heather D.
Embry, Alan C.
Skon, Cara N.
Grebe, Kristie M.
Griffin, Thomas A.
Chen, Weisan
Bennink, Jack R.
Yewdell, Jonathan W.
TI Unexpected Role for the Immunoproteasome Subunit LMP2 in Antiviral
Humoral and Innate Immune Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; T-CELL RESPONSES; INTERFERON-GAMMA; ANTIGEN PRESENTATION;
INFLUENZA INFECTION; DAMAGED PROTEINS; 20S PROTEASOME; IN-VIVO; VIRUS;
MICE
AB Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2(-/-) mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-alpha, IL-113, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-kappa B activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing. The Journal of Immunology, 2010, 184: 4115-4122.
C1 [Hensley, Scott E.; Dolan, Brian P.; David, Alexandre; Hickman, Heather D.; Embry, Alan C.; Skon, Cara N.; Grebe, Kristie M.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zanker, Damien; Chen, Weisan] Ludwig Inst Canc Res, Melbourne Ctr Clin Sci, Cell Lab T, Heidelberg, Vic, Australia.
[Griffin, Thomas A.] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA.
[Griffin, Thomas A.] Cincinnati Childrens Hosp, Med Ctr, William S Rowe Div Rheumatol, Cincinnati, OH 45229 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Room 2E13,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@mail.nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012;
OI Zanker, Damien/0000-0003-1163-9902; David, Alexandre/0000-0003-3365-1339
FU National Institute of Allergy and Infectious Diseases [R21 AI073584];
Australian National Health and Medical Research Council [ID 433608]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (R21 AI073584) and
the Australian National Health and Medical Research Council (ID 433608).
NR 42
TC 43
Z9 44
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD APR 15
PY 2010
VL 184
IS 8
BP 4115
EP 4122
DI 10.4049/jimmunol.0903003
PG 8
WC Immunology
SC Immunology
GA 582UT
UT WOS:000276625800013
PM 20228196
ER
PT J
AU Wilson, MS
Feng, CG
Barber, DL
Yarovinsky, F
Cheever, AW
Sher, A
Grigg, M
Collins, M
Fouser, L
Wynn, TA
AF Wilson, Mark S.
Feng, Carl G.
Barber, Daniel L.
Yarovinsky, Felix
Cheever, Allen W.
Sher, Alan
Grigg, Michael
Collins, Mary
Fouser, Lynette
Wynn, Thomas A.
TI Redundant and Pathogenic Roles for IL-22 in Mycobacterial, Protozoan,
and Helminth Infections
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4 T-CELLS; PROINFLAMMATORY GENE-EXPRESSION; INTESTINAL
EPITHELIAL-CELLS; TOXOPLASMA-GONDII INFECTION;
INFLAMMATORY-BOWEL-DISEASE; NITRIC-OXIDE SYNTHASE; MUCOSAL HOST-DEFENSE;
IFN-GAMMA; CROHNS-DISEASE; TUBERCULOSIS INFECTION
AB IL-22 is a member of the IL-10 cytokine family and signals through a heterodimeric receptor composed of the common IL-10R2 subunit and the IL-22R subunit. IL-10 and IL-22 both activate the STAT3 signaling pathway; however, in contrast to IL-10, relatively little is known about IL-22 in the host response to infection. In this study, using IL-22(-/-) mice, neutralizing Abs to IL-22, or both, we show that IL-22 is dispensable for the development of immunity to the opportunistic pathogens Toxoplasma gondii and Mycobacterium avium when administered via the i.p. or i.v. route, respectively. IL-22 also played little to no role in aerosol infections with Mycobacterium tuberculosis and in granuloma formation and hepatic fibrosis following chronic percutaneous infections with the helminth parasite Schistosoma mansoni. A marked pathogenic role for IL-22 was, however, identified in toxoplasmosis when infections were established by the natural oral route. Anti IL-22 Ab-treated mice developed significantly less intestinal pathology than control Ab-treated mice even though both groups displayed similar parasite burdens. The decreased gut pathology was associated with reduced IL-17A, IL-17F, TNF-alpha, and IFN-gamma expression. In contrast to the prior observations of IL-22 protective effects in the gut, these distinct findings with oral T gondii infection demonstrate that IL-22 also has the potential to contribute to pathogenic inflammation in the intestine. The IL-22 pathway has emerged as a possible target for control of inflammation in certain autoimmune diseases. Our findings suggest that few if any infectious complications would be expected with the suppression of IL-22 signaling. The Journal of Immunology, 2010, 184: 4378-4390.
C1 [Wilson, Mark S.; Wynn, Thomas A.] NIAID, Immunopathogensis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Feng, Carl G.; Barber, Daniel L.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Grigg, Michael] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Collins, Mary; Fouser, Lynette] Wyeth Res Inflammat, Cambridge, MA 02140 USA.
[Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA.
RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM twynn@hiaid.nih.gov
RI Wynn, Thomas/C-2797-2011
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 of the National
Institutes of Health.
NR 83
TC 75
Z9 77
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 APR 15
PY 2010
VL 184
IS 8
BP 4378
EP 4390
DI 10.4049/jimmunol.0903416
PG 13
WC Immunology
SC Immunology
GA 582UT
UT WOS:000276625800039
PM 20220096
ER
PT J
AU Pelak, K
Goldstein, DB
Walley, NM
Fellay, J
Ge, D
Shianna, KV
Gumbs, C
Gao, X
Maia, JM
Cronin, KD
Hussain, SK
Carrington, M
Michael, NL
Weintrob, AC
AF Pelak, Kimberly
Goldstein, David B.
Walley, Nicole M.
Fellay, Jacques
Ge, Dongliang
Shianna, Kevin V.
Gumbs, Curtis
Gao, Xiaojiang
Maia, Jessica M.
Cronin, Kenneth D.
Hussain, Shehnaz K.
Carrington, Mary
Michael, Nelson L.
Weintrob, Amy C.
CA Natl Inst Allergy Infect Dis
TI Host Determinants of HIV-1 Control in African Americans
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; WHOLE-GENOME ASSOCIATION; LINKAGE
DISEQUILIBRIUM; VIRAL LOAD; HLA; SUSCEPTIBILITY; INFECTION; GENETICS;
MODELS; SET
AB We performed a whole-genome association study of human immunodeficiency virus type 1 (HIV-1) set point among a cohort of African Americans (n = 515), and an intronic single-nucleotide polymorphism (SNP) in the HLA-B gene showed one of the strongest associations. We use a subset of patients to demonstrate that this SNP reflects the effect of the HLA-B*5703 allele, which shows a genome-wide statistically significant association with viral load set point (P = 5.6 x 10(-10)). These analyses therefore confirm a member of the HLA-B*57 group of alleles as the most important common variant that influences viral load variation in African Americans, which is consistent with what has been observed for individuals of European ancestry, among whom the most important common variant is HLA-B*5701.
C1 [Pelak, Kimberly; Goldstein, David B.; Walley, Nicole M.; Fellay, Jacques; Ge, Dongliang; Shianna, Kevin V.; Gumbs, Curtis; Maia, Jessica M.; Cronin, Kenneth D.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA.
[Gao, Xiaojiang; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21701 USA.
[Michael, Nelson L.] Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA.
[Weintrob, Amy C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
[Hussain, Shehnaz K.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA.
RP Weintrob, AC (reprint author), Walter Reed Army Med Ctr, Bldg 2,Ward 63,Room 6312, Washington, DC 20307 USA.
EM amy.weintrob@us.army.mil
RI Fellay, Jacques/A-6681-2009; Marconi, Vincent/N-3210-2014
OI Fellay, Jacques/0000-0002-8240-939X; Marconi,
Vincent/0000-0001-8409-4689
FU National Institute of Allergy and Infectious Diseases [NIAID], National
Institutes of Health [NIH] [Y1-AI5072, 5 T32 GM007754-29, AI067854];
National Cancer Institute (NCI), NIH [HHSN261200800001E]; National
Heart, Lung, and Blood Institute [UO1-AI-35042, 5-M01-RR-00052,
UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613,
UO1-AI-35041]
FX Financial support: Infectious Disease Clinical Research Program
(Department of Defense program executed through the Uniformed Services
University of the Health Sciences and funded by the National Institute
of Allergy and Infectious Diseases [NIAID], National Institutes of
Health [NIH], under interagency agreement Y1-AI5072); NIH (genetics
training grant 5 T32 GM007754-29 to K. P.); NIAID Center for HIV/AIDS
Vaccine Immunology (grant AI067854); National Cancer Institute (NCI),
NIH (contract HHSN261200800001E); Center for Cancer Research, NCI, NIH.
The Multicenter AIDS Cohort Study is funded by NIAID with supplemental
funding from NCI and the National Heart, Lung, and Blood Institute
(grants UO1-AI-35042, 5-M01-RR-00052 [GCRC], UO1-AI-35043, UO1-AI-37984,
UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041).
NR 19
TC 85
Z9 87
U1 0
U2 7
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2010
VL 201
IS 8
BP 1141
EP 1149
DI 10.1086/651382
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 568AJ
UT WOS:000275493400006
PM 20205591
ER
PT J
AU Cohen, JI
Hohman, P
Fulton, R
Turk, SP
Qin, J
Thatcher, K
Hornung, RL
AF Cohen, Jeffrey I.
Hohman, Patricia
Fulton, Rachael
Turk, Siu-Ping
Qin, Jing
Thatcher, Karen
Hornung, Ronald L.
TI Kinetics of Serum Cytokines after Primary or Repeat Vaccination with the
Smallpox Vaccine
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; IN-VIVO; ANTIVIRAL ACTIVITY;
INTERFERON-GAMMA; ADVERSE EVENTS; VIRUS VIRULENCE; BINDING-PROTEIN;
UNITED-STATES; RECEPTOR; MICE
AB Background. The smallpox vaccine is associated with more serious adverse events than any other live attenuated vaccine in use today. Although studies have examined serum cytokine levels in primary vaccine recipients at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed, and studies in revaccinated subjects have not been conducted.
Methods. We analyzed cytokine responses in both primary vaccine recipients and revaccinated subjects every other day for 2 weeks after vaccination.
Results. Primary vaccine recipients had maximal levels of granulocyte-colony-stimulating factor on days 6-7 after vaccination; peak levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor 1, interferon (IFN)-gamma, IFN-inducible protein-10 (IP-10), interleukin (IL)-6, and tissue inhibitor of metalloproteinases-1 on days 8-9 after vaccination; peak levels of soluble TNF receptor 2 and monokine induced by IFN-gamma (MIG) on days 10-11 after vaccination; and peak levels of granulocyte-macrophage-colony-stimulating factor on days 12-13 after vaccination. Primary vaccine recipients were significantly more likely to have higher peak levels of IFN-gamma, IP-10, and MIG after vaccination than were revaccinated subjects. Primary vaccine recipients were significantly more likely to have fatigue, lymphadenopathy, and headache, as well as a longer duration of these symptoms and more hours missed from work, compared with revaccinated subjects.
Conclusions. The increased frequency and duration of symptoms observed in primary vaccine recipients, compared with revaccinated subjects, paralleled the increases in serum cytokine levels in these individuals.
C1 [Cohen, Jeffrey I.] Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA.
[Hohman, Patricia; Fulton, Rachael; Turk, Siu-Ping] Lab Clin Infect Dis, Clin Studies Unit, Bethesda, MD 20892 USA.
[Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Thatcher, Karen; Hornung, Ronald L.] NCI, Clin Serv Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
RP Cohen, JI (reprint author), Lab Clin Infect Dis, Med Virol Sect, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute, National Institutes of Health [N01-C0-12400]
FX Financial support: This study was supported by the intramural research
program of the National Institute of Allergy and Infectious Diseases.
This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health (contract
N01-C0-12400).
NR 33
TC 11
Z9 11
U1 0
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2010
VL 201
IS 8
BP 1183
EP 1191
DI 10.1086/651453
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 568AJ
UT WOS:000275493400013
PM 20214479
ER
PT J
AU Schito, ML
D'Souza, MP
Owen, SM
Busch, MP
AF Schito, Marco L.
D'Souza, M. Patricia
Owen, S. Michele
Busch, Michael P.
TI Challenges for Rapid Molecular HIV Diagnostics
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRIED BLOOD SPOTS; RESOURCE-LIMITED
SETTINGS; MEDIATED ISOTHERMAL AMPLIFICATION; OF-CARE DIAGNOSTICS;
REVERSE-TRANSCRIPTION; INFECTION; INFANTS; ANTIBODY; ANTIGEN
AB The introduction of serological point-of-care assays 10 years ago dramatically changed the way that human immunodeficiency virus (HIV) infection was identified and diagnosed. Testing at the point of care has lead to a dramatic increase in the number of individuals who are screened and, most importantly, receive their HIV test result. As the AIDS epidemic continues to mature and scientific advances in prevention and treatment are evaluated and implemented, there is a need to identify acute (viremic preseroconversion) infections and to discriminate "window phase" infections from those that are serologically positive, especially in resource-limited settings, where the majority of vulnerable populations reside and where the incidence of HIV infection is highest. Rapid testing methods are now at a crossroads. There is opportunity to implement and evaluate the incremental diagnostic usefulness of new test modalities that are based on sophisticated molecular diagnostic technologies and that can be performed in settings where laboratory infrastructure is minimal. The way forward requires sound scientific judgment and an ability to further develop and implement these tests despite a variety of technical, social, and operational hurdles, to declare success.
C1 [Schito, Marco L.] NIAID, Henry Jackson Fdn Advancement Mil Med, Div Aids, NIH, Bethesda, MD 20817 USA.
[Owen, S. Michele] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
[Busch, Michael P.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
[Busch, Michael P.] Univ Calif San Francisco, Res & Sci Programs, San Francisco, CA 94143 USA.
RP Schito, ML (reprint author), NIAID, Henry Jackson Fdn Advancement Mil Med, Div Aids, NIH, 6700 Rockledge Dr, Bethesda, MD 20817 USA.
EM schitom@niaid.nih.gov
FU National Institutes of Allergy and Infectious Diseases; Department of
Health and Human Services [HHSN272200800014C]
FX Federal funds from the National Institutes of Allergy and Infectious
Diseases, Department of Health and Human Services (contract number
HHSN272200800014C).
NR 47
TC 19
Z9 20
U1 1
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2010
VL 201
SU 1
BP S1
EP S6
DI 10.1086/650394
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 568AK
UT WOS:000275493500001
PM 20225941
ER
PT J
AU Zhang, N
Appella, DH
AF Zhang, Ning
Appella, Daniel H.
TI Advantages of Peptide Nucleic Acids as Diagnostic Platforms for
Detection of Nucleic Acids in Resource-Limited Settings
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNA MOLECULAR BEACONS; REAL-TIME PCR;
LUNG-CANCER; DNA; HYBRIDIZATION; BACKBONE; THERAPY; ASSAY
AB Peptide nucleic acids are a class of nondegradable oligonucleotide mimics that can be used as probes for nucleic acid sequences and could convey the necessary stability to be a diagnostic tool for use in a resource-limited setting. In this review, there is a brief introduction to the field of peptide nucleic acids and their potential benefits as probes for DNA and RNA sequences, followed by highlights of ways by which peptide nucleic acids could benefit a number of established diagnostic tools for human immunodeficiency virus detection.
C1 [Zhang, Ning; Appella, Daniel H.] NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Appella, DH (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health
FX Intramural Research program at National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health.
NR 22
TC 12
Z9 13
U1 1
U2 9
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2010
VL 201
SU 1
BP S42
EP S45
DI 10.1086/650389
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 568AK
UT WOS:000275493500006
PM 20225945
ER
PT J
AU Wade, HE
Kobayashi, S
Eaton, ML
Jansen, MS
Lobenhofer, EK
Lupien, M
Geistlinger, TR
Zhu, WC
Nevins, JR
Brown, M
Otteson, DC
McDonnell, DP
AF Wade, Hilary E.
Kobayashi, Sakiko
Eaton, Matthew L.
Jansen, Michelle S.
Lobenhofer, Edward K.
Lupien, Mathieu
Geistlinger, Timothy R.
Zhu, Wencheng
Nevins, Joseph R.
Brown, Myles
Otteson, Deborah C.
McDonnell, Donald P.
TI Multimodal Regulation of E2F1 Gene Expression by Progestins
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID CELL-CYCLE PROGRESSION; BREAST-CANCER CELLS; HUMAN
PROGESTERONE-RECEPTORS; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL REGULATOR;
RETINOBLASTOMA PROTEIN; FUNCTIONAL DOMAINS; ACTIVATION; PROLIFERATION;
KINASES
AB An analysis of mRNA expression in T47D breast cancer cells treated with the synthetic progestin R5020 revealed a subset of progesterone receptor (PR) target genes that are enriched for E2F binding sites. Following up on this observation, we determined that PR-B acts in both direct and indirect manners to positively upregulate E2F1 expression in T47D cells. The direct effects of PR on E2F1 expression were confirmed by chromatin immunoprecipitation (ChIP) analysis, which indicated that the agonist-bound receptor was recruited to several enhancer elements proximal to the E2F1 transcript. However, we also noted that cycloheximide partially inhibits R5020 induction of E2F1 expression, indicating that the ligand-dependent actions of PR on this gene may involve additional indirect regulatory pathways. In support of this hypothesis, we demonstrated that treatment with R5020 significantly increases both hyperphosphorylation of Rb and recruitment of E2F1 to its own promoter, thus activating a positive feedback loop that further amplifies its transcription. Furthermore, we established that PR-mediated induction of Kruppel-like factor 15 (KLF15), which can bind to GC-rich DNA within the E2F1 promoter, is required for maximal induction of E2F1 expression by progestins. Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR.
C1 [Wade, Hilary E.; Kobayashi, Sakiko; Eaton, Matthew L.; Jansen, Michelle S.; McDonnell, Donald P.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Lobenhofer, Edward K.] NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA.
[Lupien, Mathieu; Geistlinger, Timothy R.; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA.
[Zhu, Wencheng; Nevins, Joseph R.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Otteson, Deborah C.] Univ Houston, Coll Optometry, Houston, TX 77204 USA.
RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA.
EM donald.mcdonnell@duke.edu
RI Eaton, Matthew/C-4408-2011;
OI Brown, Myles/0000-0002-8213-1658; Otteson, Deborah/0000-0001-6093-6837
FU DOD [W81XWH-06-1-0745]; NIH [DK048807, EY13499, DK074967, CA089393,
CA080111]
FX This work was supported by DOD grant W81XWH-06-1-0745 (H. E. W.) and by
NIH grants DK048807 (D. P. M.); EY13499 (D.C.O.); and DK074967,
CA089393, and CA080111 (M. B.).
NR 39
TC 18
Z9 18
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR 15
PY 2010
VL 30
IS 8
BP 1866
EP 1877
DI 10.1128/MCB.01060-09
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 574HV
UT WOS:000275980900001
PM 20123965
ER
PT J
AU Yasmeen, A
Riazuddin, SA
Kaul, H
Mohsin, S
Khan, M
Qazi, ZA
Nasir, IA
Zafar, AU
Khan, SN
Husnain, T
Akram, J
Hejtmancik, JF
Riazuddin, S
AF Yasmeen, Afshan
Riazuddin, S. Amer
Kaul, Haiba
Mohsin, Sadia
Khan, Mohsin
Qazi, Zaheeruddin A.
Nasir, Idrees A.
Zafar, Ahmad U.
Khan, Shaheen N.
Husnain, Tayyab
Akram, Javed
Hejtmancik, J. Fielding
Riazuddin, Sheikh
TI Autosomal recessive congenital cataract in consanguineous Pakistani
families is associated with mutations in GALK1
SO MOLECULAR VISION
LA English
DT Article
ID MOLECULAR-GENETICS; NONSENSE MUTATION; LOCUS; BLINDNESS; MAPS
AB Purpose: To identify the pathogenic mutations responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
Methods: All affected individuals underwent detailed ophthalmologic and medical examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was performed with polymorphic microsatellite markers on genomic DNA from affected and unaffected family members and logarithm of odds (LOD) scores were calculated. All coding exons of galactokinase (GALK1) were sequenced to identify pathogenic lesions.
Results: Clinical records and ophthalmological examinations suggested that affected individuals have nuclear cataracts. Linkage analysis localized the critical interval to chromosome 17q with a maximum LOD score of 5.54 at theta=0, with D17S785 in family PKCC030. Sequencing of GALK1, a gene present in the critical interval, identified a single base pair deletion: c.410delG, which results in a frame shift leading to a premature termination of GALK1: p. G137fsX27. Additionally, we identified a missense mutation: c.416T>C, in family PKCC055 that results in substitution of a leucine residue at position 139 with a proline residue: p.L139P, and is predicted to be deleterious to the native GALK1 structure.
Conclusions: Here, we report pathogenic mutations in GALK1 that are responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
C1 [Yasmeen, Afshan; Riazuddin, S. Amer; Kaul, Haiba; Mohsin, Sadia; Khan, Mohsin; Nasir, Idrees A.; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust, Lahore, Pakistan.
[Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan.
EM riaz@aimrc.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015
FU Higher Education Commission; Ministry of Science and Technology
Islamabad, Pakistan
FX The authors are grateful to the family members for their participation
in this study. This study was supported, in part by Higher Education
Commission and Ministry of Science and Technology Islamabad, Pakistan.
NR 22
TC 12
Z9 12
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 15
PY 2010
VL 16
IS 76-78
BP 682
EP 688
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 619MG
UT WOS:000279433700002
PM 20405025
ER
PT J
AU Hudson, TJ
Anderson, W
Aretz, A
Barker, AD
Bell, C
Bernabe, RR
Bhan, MK
Calvo, F
Eerola, I
Gerhard, DS
Guttmacher, A
Guyer, M
Hemsley, FM
Jennings, JL
Kerr, D
Klatt, P
Kolar, P
Kusuda, J
Lane, DP
Laplace, F
Lu, YY
Nettekoven, G
Ozenberger, B
Peterson, J
Rao, TS
Remacle, J
Schafer, AJ
Shibata, T
Stratton, MR
Vockley, JG
Watanabe, K
Yang, HM
Yuen, MMF
Knoppers, M
Bobrow, M
Cambon-Thomsen, A
Dressler, LG
Dyke, SOM
Joly, Y
Kato, K
Kennedy, KL
Nicolas, P
Parker, MJ
Rial-Sebbag, E
Romeo-Casabona, CM
Shaw, KM
Wallace, S
Wiesner, GL
Zeps, N
Lichter, P
Biankin, AV
Chabannon, C
Chin, L
Clement, B
de Alava, E
Degos, F
Ferguson, ML
Geary, P
Hayes, DN
Johns, AL
Nakagawa, H
Penny, R
Piris, MA
Sarin, R
Scarpa, A
Shibata, T
van de Vijver, M
Futreal, PA
Aburatani, H
Bayes, M
Bowtell, DDL
Campbell, PJ
Estivill, X
Grimmond, SM
Gut, I
Hirst, M
Lopez-Otin, C
Majumder, P
Marra, M
Nakagawa, H
Ning, ZM
Puente, XS
Ruan, YJ
Shibata, T
Stratton, MR
Stunnenberg, HG
Swerdlow, H
Velculescu, VE
Wilson, RK
Xue, HH
Yang, L
Spellman, PT
Bader, GD
Boutros, PC
Campbell, PJ
Flicek, P
Getz, G
Guigo, R
Guo, GW
Haussler, D
Heath, S
Hubbard, TJ
Jiang, T
Jones, SM
Li, QB
Lopez-Bigas, N
Luo, RB
Pearson, JV
Puente, XS
Quesada, V
Raphael, BJ
Sander, C
Shibata, T
Speed, TP
Stuart, JM
Teague, JW
Totoki, Y
Tsunoda, T
Valencia, A
Wheeler, DA
Wu, HL
Zhao, SC
Zhou, GY
Stein, LD
Guigo, R
Hubbard, TJ
Joly, Y
Jones, SM
Lathrop, M
Lopez-Bigas, N
Ouellette, BFF
Spellman, PT
Teague, JW
Thomas, G
Valencia, A
Yoshida, T
Kennedy, KL
Axton, M
Dyke, SOM
Futreal, PA
Gunter, C
Guyer, M
McPherson, JD
Miller, LJ
Ozenberger, B
Kasprzyk, A
Zhang, JJ
Haider, SA
Wang, JX
Yung, CK
Cross, A
Liang, Y
Gnaneshan, S
Guberman, J
Hsu, J
Bobrow, M
Chalmers, DRC
Hasel, KW
Joly, Y
Kaan, TSH
Kennedy, KL
Knoppers, BM
Lowrance, WW
Masui, T
Nicolas, P
Rial-Sebbag, E
Rodriguez, LL
Vergely, C
Yoshida, T
Grimmond, SM
Biankin, AV
Bowtell, DDL
Cloonan, N
Defazio, A
Eshleman, JR
Etemadmoghadam, D
Gardiner, BA
Kench, JG
Scarpa, A
Sutherland, RL
Tempero, MA
Waddell, NJ
Wilson, PJ
Gallinger, S
Tsao, MS
Shaw, PA
Petersen, GM
Mukhopadhyay, D
Chin, L
DePinho, RA
Thayer, S
Muthuswamy, L
Shazand, K
Beck, T
Sam, M
Timms, L
Ballin, V
Lu, YY
Ji, JF
Zhang, XQ
Chen, F
Hu, XD
Zhou, GY
Yang, Q
Tian, G
Zhang, LH
Xing, XF
Li, XH
Zhu, ZG
Yu, YY
Yu, J
Yang, HM
Lathrop, M
Tost, J
Brennan, P
Holcatova, I
Zaridze, D
Brazma, A
Egevad, L
Prokhortchouk, E
Banks, RE
Uhlen, M
Cambon-Thomsen, A
Viksna, J
Ponten, F
Skryabin, K
Stratton, MR
Futreal, PA
Birney, E
Borg, A
Borresen-Dale, AL
Caldas, C
Foekens, JA
Martin, S
Reis-Filho, JS
Richardson, AL
Sotiriou, C
Stunnenberg, HG
Thomas, G
van de Vijver, M
van't Veer, L
Birnbaum, D
Blanche, H
Boucher, P
Boyault, S
Chabannon, C
Gut, I
Masson-Jacquemier, JD
Lathrop, M
Pauporte, I
Pivot, X
Vincent-Salomon, A
Tabone, E
Theillet, C
Thomas, G
Tost, J
Treilleux, I
Bioulac-Sage, P
Clement, B
Decaens, T
Degos, F
Franco, D
Gut, I
Gut, M
Heath, S
Lathrop, M
Samuel, D
Thomas, G
Zucman-Rossi, J
Lichter, P
Eils, R
Brors, B
Korbel, JO
Korshunov, A
Landgraf, P
Lehrach, H
Pfister, S
Radlwimmer, B
Reifenberger, G
Taylor, MD
von Kalle, C
Majumder, PP
Sarin, R
Scarpa, A
Pederzoli, P
Lawlor, RT
Delledonne, M
Bardelli, A
Biankin, AV
Grimmond, SM
Gress, T
Klimstra, D
Zamboni, G
Shibata, T
Nakamura, Y
Nakagawa, H
Kusuda, J
Tsunoda, T
Miyano, S
Aburatani, H
Kato, K
Fujimoto, A
Yoshida, T
Campo, E
Lopez-Otin, C
Estivill, X
Guigo, R
de Sanjose, S
Piris, MA
Montserrat, E
Gonzalez-Diaz, M
Puente, XS
Jares, P
Valencia, A
Himmelbaue, H
Quesada, V
Bea, S
Stratton, MR
Futreal, PA
Campbell, PJ
Vincent-Salomon, A
Richardson, AL
Reis-Filho, JS
van de Vijver, M
Thomas, G
Masson-Jacquemier, JD
Aparicio, S
Borg, A
Borresen-Dale, AL
Caldas, C
Foekens, JA
Stunnenberg, HG
van't Veer, L
Easton, DF
Spellman, PT
Martin, S
Chin, L
Collins, FS
Compton, CC
Ferguson, ML
Getz, G
Gunter, C
Guyer, M
Hayes, DN
Lander, ES
Ozenberger, B
Penny, R
Peterson, J
Sander, C
Speed, TP
Spellman, PT
Wheeler, DA
Wilson, RK
Chin, L
Knoppers, BM
Lander, ES
Lichter, P
Stratton, MR
Bobrow, M
Burke, W
Collins, FS
DePinho, RA
Easton, DF
Futreal, PA
Green, AR
Guyer, M
Hamilton, SR
Hubbard, TJ
Kallioniemi, OP
Kennedy, KL
Ley, TJ
Liu, ET
Lu, YY
Majumder, P
Marra, M
Ozenberger, B
Peterson, J
Schafer, AJ
Spellman, PT
Stunnenberg, HG
Wainwright, BJ
Wilson, RK
Yang, HM
AF Hudson, Thomas J.
Anderson, Warwick
Aretz, Axel
Barker, Anna D.
Bell, Cindy
Bernabe, Rosa R.
Bhan, M. K.
Calvo, Fabien
Eerola, Iiro
Gerhard, Daniela S.
Guttmacher, Alan
Guyer, Mark
Hemsley, Fiona M.
Jennings, Jennifer L.
Kerr, David
Klatt, Peter
Kolar, Patrik
Kusuda, Jun
Lane, David P.
Laplace, Frank
Lu, Youyong
Nettekoven, Gerd
Ozenberger, Brad
Peterson, Jane
Rao, T. S.
Remacle, Jacques
Schafer, Alan J.
Shibata, Tatsuhiro
Stratton, Michael R.
Vockley, Joseph G.
Watanabe, Koichi
Yang, Huanming
Yuen, Matthew M. F.
Knoppers, M.
Bobrow, Martin
Cambon-Thomsen, Anne
Dressler, Lynn G.
Dyke, Stephanie O. M.
Joly, Yann
Kato, Kazuto
Kennedy, Karen L.
Nicolas, Pilar
Parker, Michael J.
Rial-Sebbag, Emmanuelle
Romeo-Casabona, Carlos M.
Shaw, Kenna M.
Wallace, Susan
Wiesner, Georgia L.
Zeps, Nikolajs
Lichter, Peter
Biankin, Andrew V.
Chabannon, Christian
Chin, Lynda
Clement, Bruno
de Alava, Enrique
Degos, Francoise
Ferguson, Martin L.
Geary, Peter
Hayes, D. Neil
Johns, Amber L.
Nakagawa, Hidewaki
Penny, Robert
Piris, Miguel A.
Sarin, Rajiv
Scarpa, Aldo
Shibata, Tatsuhiro
van de Vijver, Marc
Futreal, P. Andrew
Aburatani, Hiroyuki
Bayes, Monica
Bowtell, David D. L.
Campbell, Peter J.
Estivill, Xavier
Grimmond, Sean M.
Gut, Ivo
Hirst, Martin
Lopez-Otin, Carlos
Majumder, Partha
Marra, Marco
Nakagawa, Hidewaki
Ning, Zemin
Puente, Xose S.
Ruan, Yijun
Shibata, Tatsuhiro
Stratton, Michael R.
Stunnenberg, Hendrik G.
Swerdlow, Harold
Velculescu, Victor E.
Wilson, Richard K.
Xue, Hong H.
Yang, Liu
Spellman, Paul T.
Bader, Gary D.
Boutros, Paul C.
Campbell, Peter J.
Flicek, Paul
Getz, Gad
Guigo, Roderic
Guo, Guangwu
Haussler, David
Heath, Simon
Hubbard, Tim J.
Jiang, Tao
Jones, Steven M.
Li, Qibin
Lopez-Bigas, Nuria
Luo, Ruibang
Pearson, John V.
Puente, Xose S.
Quesada, Victor
Raphael, Benjamin J.
Sander, Chris
Shibata, Tatsuhiro
Speed, Terence P.
Stuart, Joshua M.
Teague, Jon W.
Totoki, Yasushi
Tsunoda, Tatsuhiko
Valencia, Alfonso
Wheeler, David A.
Wu, Honglong
Zhao, Shancen
Zhou, Guangyu
Stein, Lincoln D.
Guigo, Roderic
Hubbard, Tim J.
Joly, Yann
Jones, Steven M.
Lathrop, Mark
Lopez-Bigas, Nuria
Ouellette, B. F. Francis
Spellman, Paul T.
Teague, Jon W.
Thomas, Gilles
Valencia, Alfonso
Yoshida, Teruhiko
Kennedy, Karen L.
Axton, Myles
Dyke, Stephanie O. M.
Futreal, P. Andrew
Gunter, Chris
Guyer, Mark
McPherson, John D.
Miller, Linda J.
Ozenberger, Brad
Kasprzyk, Arek
Zhang, Junjun
Haider, Syed A.
Wang, Jianxin
Yung, Christina K.
Cross, Anthony
Liang, Yong
Gnaneshan, Saravanamuttu
Guberman, Jonathan
Hsu, Jack
Bobrow, Martin
Chalmers, Don R. C.
Hasel, Karl W.
Joly, Yann
Kaan, Terry S. H.
Kennedy, Karen L.
Knoppers, Bartha M.
Lowrance, William W.
Masui, Tohru
Nicolas, Pilar
Rial-Sebbag, Emmanuelle
Rodriguez, Laura Lyman
Vergely, Catherine
Yoshida, Teruhiko
Grimmond, Sean M.
Biankin, Andrew V.
Bowtell, David D. L.
Cloonan, Nicole
Defazio, Anna
Eshleman, James R.
Etemadmoghadam, Dariush
Gardiner, Brooke A.
Kench, James G.
Scarpa, Aldo
Sutherland, Robert L.
Tempero, Margaret A.
Waddell, Nicola J.
Wilson, Peter J.
Gallinger, Steve
Tsao, Ming-Sound
Shaw, Patricia A.
Petersen, Gloria M.
Mukhopadhyay, Debabrata
Chin, Lynda
DePinho, Ronald A.
Thayer, Sarah
Muthuswamy, Lakshmi
Shazand, Kamran
Beck, Timothy
Sam, Michelle
Timms, Lee
Ballin, Vanessa
Lu, Youyong
Ji, Jiafu
Zhang, Xiuqing
Chen, Feng
Hu, Xueda
Zhou, Guangyu
Yang, Qi
Tian, Geng
Zhang, Lianhai
Xing, Xiaofang
Li, Xianghong
Zhu, Zhenggang
Yu, Yingyan
Yu, Jun
Yang, Huanming
Lathrop, Mark
Tost, Joerg
Brennan, Paul
Holcatova, Ivana
Zaridze, David
Brazma, Alvis
Egevad, Lars
Prokhortchouk, Egor
Banks, Rosamonde Elizabeth
Uhlen, Mathias
Cambon-Thomsen, Anne
Viksna, Juris
Ponten, Fredrik
Skryabin, Konstantin
Stratton, Michael R.
Futreal, P. Andrew
Birney, Ewan
Borg, Ake
Borresen-Dale, Anne-Lise
Caldas, Carlos
Foekens, John A.
Martin, Sancha
Reis-Filho, Jorge S.
Richardson, Andrea L.
Sotiriou, Christos
Stunnenberg, Hendrik G.
Thomas, Gilles
van de Vijver, Marc
van't Veer, Laura
Birnbaum, Daniel
Blanche, Helene
Boucher, Pascal
Boyault, Sandrine
Chabannon, Christian
Gut, Ivo
Masson-Jacquemier, Jocelyne D.
Lathrop, Mark
Pauporte, Iris
Pivot, Xavier
Vincent-Salomon, Anne
Tabone, Eric
Theillet, Charles
Thomas, Gilles
Tost, Joerg
Treilleux, Isabelle
Bioulac-Sage, Paulette
Clement, Bruno
Decaens, Thomas
Degos, Francoise
Franco, Dominique
Gut, Ivo
Gut, Marta
Heath, Simon
Lathrop, Mark
Samuel, Didier
Thomas, Gilles
Zucman-Rossi, Jessica
Lichter, Peter
Eils, Roland
Brors, Benedikt
Korbel, Jan O.
Korshunov, Andrey
Landgraf, Pablo
Lehrach, Hans
Pfister, Stefan
Radlwimmer, Bernhard
Reifenberger, Guido
Taylor, Michael D.
von Kalle, Christof
Majumder, Partha P.
Sarin, Rajiv
Scarpa, Aldo
Pederzoli, Paolo
Lawlor, Rita T.
Delledonne, Massimo
Bardelli, Alberto
Biankin, Andrew V.
Grimmond, Sean M.
Gress, Thomas
Klimstra, David
Zamboni, Giuseppe
Shibata, Tatsuhiro
Nakamura, Yusuke
Nakagawa, Hidewaki
Kusuda, Jun
Tsunoda, Tatsuhiko
Miyano, Satoru
Aburatani, Hiroyuki
Kato, Kazuto
Fujimoto, Akihiro
Yoshida, Teruhiko
Campo, Elias
Lopez-Otin, Carlos
Estivill, Xavier
Guigo, Roderic
de Sanjose, Silvia
Piris, Miguel A.
Montserrat, Emili
Gonzalez-Diaz, Marcos
Puente, Xose S.
Jares, Pedro
Valencia, Alfonso
Himmelbaue, Heinz
Quesada, Victor
Bea, Silvia
Stratton, Michael R.
Futreal, P. Andrew
Campbell, Peter J.
Vincent-Salomon, Anne
Richardson, Andrea L.
Reis-Filho, Jorge S.
van de Vijver, Marc
Thomas, Gilles
Masson-Jacquemier, Jocelyne D.
Aparicio, Samuel
Borg, Ake
Borresen-Dale, Anne-Lise
Caldas, Carlos
Foekens, John A.
Stunnenberg, Hendrik G.
van't Veer, Laura
Easton, Douglas F.
Spellman, Paul T.
Martin, Sancha
Chin, Lynda
Collins, Francis S.
Compton, Carolyn C.
Ferguson, Martin L.
Getz, Gad
Gunter, Chris
Guyer, Mark
Hayes, D. Neil
Lander, Eric S.
Ozenberger, Brad
Penny, Robert
Peterson, Jane
Sander, Chris
Speed, Terence P.
Spellman, Paul T.
Wheeler, David A.
Wilson, Richard K.
Chin, Lynda
Knoppers, Bartha M.
Lander, Eric S.
Lichter, Peter
Stratton, Michael R.
Bobrow, Martin
Burke, Wylie
Collins, Francis S.
DePinho, Ronald A.
Easton, Douglas F.
Futreal, P. Andrew
Green, Anthony R.
Guyer, Mark
Hamilton, Stanley R.
Hubbard, Tim J.
Kallioniemi, Olli P.
Kennedy, Karen L.
Ley, Timothy J.
Liu, Edison T.
Lu, Youyong
Majumder, Partha
Marra, Marco
Ozenberger, Brad
Peterson, Jane
Schafer, Alan J.
Spellman, Paul T.
Stunnenberg, Hendrik G.
Wainwright, Brandon J.
Wilson, Richard K.
Yang, Huanming
CA Int Canc Genome Consortium
TI International network of cancer genome projects
SO NATURE
LA English
DT Article
ID MYELOID-LEUKEMIA GENOME; SOMATIC MUTATIONS; BREAST-CANCER; GENE;
PATHWAYS; LANDSCAPES; DATABASE
AB The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
C1 [Jennings, Jennifer L.; Boutros, Paul C.; Stein, Lincoln D.; Ouellette, B. F. Francis; McPherson, John D.; Kasprzyk, Arek; Zhang, Junjun; Wang, Jianxin; Yung, Christina K.; Cross, Anthony; Liang, Yong; Gnaneshan, Saravanamuttu; Guberman, Jonathan; Hsu, Jack; Muthuswamy, Lakshmi; Shazand, Kamran; Beck, Timothy; Sam, Michelle; Timms, Lee; Ballin, Vanessa] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Hudson, Thomas J.; Anderson, Warwick] Natl Hlth & Med Res Council, Canberra, ACT 2601, Australia.
[Aretz, Axel] German Aerosp Ctr DLR, Project Management Agcy, D-53175 Bonn, Germany.
[Barker, Anna D.; Gerhard, Daniela S.; Vockley, Joseph G.; Shaw, Kenna M.; Compton, Carolyn C.] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bell, Cindy; Hasel, Karl W.] Genome Canada, Ottawa, ON K2P 1P1, Canada.
[Bernabe, Rosa R.; Klatt, Peter] Minist Sci & Innovat, Secretariat State Res, Madrid 28027, Spain.
[Bhan, M. K.; Rao, T. S.] Govt India, Minist Sci & Technol, Dept Biotechnol, New Delhi 110003, India.
[Calvo, Fabien; Chabannon, Christian; Boucher, Pascal; Pauporte, Iris] Natl Canc Inst, F-92513 Boulogne, France.
[Eerola, Iiro; Kolar, Patrik; Remacle, Jacques] European Commiss, Hlth Res Directorate, Genom & Syst Biol Unit, B-1049 Brussels, Belgium.
[Guttmacher, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Rodriguez, Laura Lyman] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Hemsley, Fiona M.; Lane, David P.] Canc Res UK, London WC2A 3PX, England.
[Kerr, David] Qatar Fdn, Sidra Med & Res Ctr, Doha, Qatar.
Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England.
[Kusuda, Jun; Masui, Tohru] Natl Inst Biomed Innovat, Osaka 5670085, Japan.
[Laplace, Frank] Fed Minist Educ & Res, Div Mol Life Sci, D-11055 Berlin, Germany.
[Lu, Youyong; Ji, Jiafu; Chen, Feng; Zhang, Lianhai; Xing, Xiaofang; Li, Xianghong] Peking Univ, Sch Oncol, Beijing Canc Inst & Hosp, Beijing 100142, Peoples R China.
[Nettekoven, Gerd] German Canc Aid, D-53113 Bonn, Germany.
[Schafer, Alan J.] Wellcome Trust Res Labs, London NW1 2BE, England.
[Shibata, Tatsuhiro; Totoki, Yasushi; Yoshida, Teruhiko; Zaridze, David] Natl Canc Ctr, Chuo Ku, Tokyo 1040045, Japan.
[Stratton, Michael R.; Dyke, Stephanie O. M.; Kennedy, Karen L.; Futreal, P. Andrew; Campbell, Peter J.; Ning, Zemin; Swerdlow, Harold; Hubbard, Tim J.; Teague, Jon W.; Martin, Sancha] Hinxton, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Watanabe, Koichi] RIKEN, Yokohama Inst, Kanagawa, Japan.
[Yang, Huanming; Guo, Guangwu; Jiang, Tao; Li, Qibin; Luo, Ruibang; Wu, Honglong; Zhao, Shancen; Zhou, Guangyu; Zhang, Xiuqing; Hu, Xueda; Yang, Qi; Tian, Geng] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
[Yuen, Matthew M. F.] Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China.
[Knoppers, M.; Joly, Yann; Wallace, Susan; Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada.
[Knoppers, M.; Wallace, Susan] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada.
[Bobrow, Martin] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England.
[Cambon-Thomsen, Anne; Rial-Sebbag, Emmanuelle] Fac Med Toulouse, INSERM, U558, F-31073 Toulouse, France.
[Dressler, Lynn G.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC 27599 USA.
[Kato, Kazuto] Kyoto Univ, Grad Sch Biostudies, Inst Integrated Cell Mat Sci, Inst Res Humanities, Kyoto 6068501, Japan.
[Nicolas, Pilar; Romeo-Casabona, Carlos M.] Univ Deusto, Interuniv Chair Law & Human Genome, Bizkaia 48007, Spain.
[Parker, Michael J.] Univ Oxford, Ethox Ctr, Oxford OX3 7LF, England.
[Wiesner, Georgia L.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Wiesner, Georgia L.] Univ Hosp Cleveland, Case Med Ctr, Ctr Human Genet, Cleveland, OH 44106 USA.
St John God Pathol, Subiaco, WA 6008, Australia.
Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Zeps, Nikolajs] Univ Western Australia, Sch Surg, Nedlands, WA 6009, Australia.
[Lichter, Peter; Eils, Roland; Brors, Benedikt; Pfister, Stefan; Radlwimmer, Bernhard] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Biankin, Andrew V.; Johns, Amber L.; Kench, James G.; Sutherland, Robert L.] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW 2010, Australia.
Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia.
[Birnbaum, Daniel; Chabannon, Christian; Masson-Jacquemier, Jocelyne D.] Inst J Paoli I Calmettes, F-13273 Marseille, France.
[Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Clement, Bruno] INSERM, U991, F-35043 Rennes, France.
[de Alava, Enrique; Gonzalez-Diaz, Marcos] Univ Salamanca, Ctr Invest Canc, Univ Hosp, Dept Hematol, Salamanca 37007, Spain.
[Degos, Francoise] Hop Beaujon, F-92110 Clichy, France.
[Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
[Geary, Peter] Canadian Tumour Repository Network, Winnipeg, MB R3M 0V5, Canada.
[Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Lineberger Comprehens Canc Ctr, Dept Internal Med, Chapel Hill, NC 27599 USA.
[Nakagawa, Hidewaki; Tsunoda, Tatsuhiko; Nakamura, Yusuke; Fujimoto, Akihiro] RIKEN, Ctr Genom Med, Kanagawa 2300045, Japan.
[Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Piris, Miguel A.] Spanish Natl Canc Res Ctr, Mol Pathol Programme, Madrid 28029, Spain.
[Sarin, Rajiv] Tata Mem Hosp, Adv Ctr Treatment, Res & Educ Canc, Navi Mumbai 41021, Maharashtra, India.
[Scarpa, Aldo; Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37134 Verona, Italy.
[Scarpa, Aldo; Lawlor, Rita T.] Verona Univ Hosp, Ctr Appl Res Canc ARC NET, I-37134 Verona, Italy.
[van de Vijver, Marc; van't Veer, Laura] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
[van de Vijver, Marc] Acad Med Ctr, NL-1015 AZ Amsterdam, Netherlands.
[Aburatani, Hiroyuki] Univ Tokyo, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan.
[Bayes, Monica; Estivill, Xavier; Himmelbaue, Heinz] Pompeu Fabra Univ, Ctr Genom Regulat, Barcelona 08003, Spain.
[Bayes, Monica] Biomed Res Ctr CIBERESP, Publ Hlth & Epidemiol Network, Barcelona 08003, Catalonia, Spain.
[Bowtell, David D. L.; Etemadmoghadam, Dariush] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
[Etemadmoghadam, Dariush] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.
Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
[Grimmond, Sean M.; Pearson, John V.; Cloonan, Nicole; Gardiner, Brooke A.; Waddell, Nicola J.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4067, Australia.
[Gut, Ivo; Heath, Simon; Lathrop, Mark; Tost, Joerg] CEA, DSV, IG Ctr Natl Genotypage, F-91057 Evry, France.
[Hirst, Martin; Marra, Marco; Jones, Steven M.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Lopez-Otin, Carlos; Puente, Xose S.; Quesada, Victor] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain.
[Majumder, Partha; Majumder, Partha P.] Natl Inst Biomed Genom, Kalyani 741251, W Bengal, India.
[McPherson, John D.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
[Ruan, Yijun; Liu, Edison T.] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore.
[Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
[Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
[Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA.
[Xue, Hong H.] HKUST, Appl Genom Ctr, Fok Ying Grad Sch, Hong Kong, Hong Kong, Peoples R China.
[Xue, Hong H.] Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Yang, Liu] Zhejiang Univ, Inst Canc, Hangzhou 310009, Zhejiang, Peoples R China.
[Spellman, Paul T.] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94510 USA.
[Bader, Gary D.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
[Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
[Flicek, Paul; Brazma, Alvis; Birney, Ewan; Korbel, Jan O.] Hinxton, European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
[Getz, Gad; Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
[Getz, Gad] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Guigo, Roderic] Univ Pompeu Fabra, Spanish Natl Bioinformat Inst, Barcelona 08003, Spain.
Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona 08003, Spain.
[Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
[Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Lopez-Bigas, Nuria] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona 08003, Spain.
[Raphael, Benjamin J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
[Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
[Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
[Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
[Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Stuart, Joshua M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
[Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Spanish Natl Bioinformat Inst, Madrid 28029, Spain.
[Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomputing Programme, Madrid 28029, Spain.
[Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Blanche, Helene; Gut, Marta] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
[Thomas, Gilles] Univ Lyon 1, F-69622 Villeurbanne, France.
Fdn Synergie Lyon Canc, F-69008 Lyon, France.
[Axton, Myles] Natl Genet, New York, NY 10013 USA.
[Gunter, Chris] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Miller, Linda J.] Nat & Nat Res Journals, New York, NY 10013 USA.
[Haider, Syed A.] Univ Cambridge, Comp Lab, Cambridge CB3 0FD, England.
[Chalmers, Don R. C.] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia.
[Kaan, Terry S. H.] Natl Univ Singapore, Fac Law, Singapore 259776, Singapore.
[Lowrance, William W.] Consultant Hlth Res Eth & Policy, F-34280 La Grande Motte, France.
[Vergely, Catherine] Inst Gustave Roussy, ISIS 39, F-94805 Villejuif, France.
[Defazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia.
[Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia.
[Eshleman, James R.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
[Kench, James G.] Univ Sydney, Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2050, Australia.
[Tempero, Margaret A.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
[Gallinger, Steve] Toronto Gen Hosp, Dept Gen Surg, Toronto, ON M5G 2C4, Canada.
[Gallinger, Steve] Samuel Lunenfeld Res Inst, Toronto, ON M5S 1A1, Canada.
[Tsao, Ming-Sound] Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 2M9, Canada.
[Tsao, Ming-Sound] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada.
[Shaw, Patricia A.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
[Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Mukhopadhyay, Debabrata] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA.
[Thayer, Sarah] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Zhu, Zhenggang; Yu, Yingyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China.
[Yu, Jun] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12108, Czech Republic.
[Zaridze, David] NN Blokhin Russian Canc Res Ctr, Dept Epidemiol & Prevent, Moscow 115478, Russia.
[Egevad, Lars] Karolinska Univ Hosp, Karolinska Inst, SE-17176 Stockholm, Sweden.
[Prokhortchouk, Egor] Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia.
[Banks, Rosamonde Elizabeth] St James Univ Hosp, Leeds Inst Mol Med, Canc Res UK Ctr, Leeds LS9 7TF, W Yorkshire, England.
[Uhlen, Mathias] KTH Royal Inst Technol, Sci Life Lab, SE-10044 Stockholm, Sweden.
[Viksna, Juris] Univ Latvia, Inst Math & Comp Sci, LV-1459 Riga, Latvia.
[Ponten, Fredrik] Uppsala Univ, SE-75105 Uppsala, Sweden.
[Skryabin, Konstantin] Kurchatov Sci Ctr, Moscow 123182, Russia.
[Borg, Ake] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden.
[Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, N-0310 Oslo, Norway.
[Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, N-0316 Oslo, Norway.
[Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England.
[Caldas, Carlos] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
[Foekens, John A.] Josephine Nefkens Inst, Erasmus MC Rotterdam, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands.
[Foekens, John A.] Canc Genom Ctr, NL-3015 CE Rotterdam, Netherlands.
[Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Boyault, Sandrine; Tabone, Eric; Treilleux, Isabelle] Ctr Leon Berard, F-69373 Lyon, France.
[Sotiriou, Christos] Inst Jules Bordet, B-1000 Brussels, Belgium.
[Pivot, Xavier] Hop Jean Minjoz, F-25030 Besancon, France.
[Vincent-Salomon, Anne] Inst Curie, F-75231 Paris, France.
[Theillet, Charles] Ctr Val Aurelle, F-34298 Montpellier, France.
[Bioulac-Sage, Paulette] Hop Pellegrin, F-33076 Bordeaux, France.
[Decaens, Thomas] Hop Henri Mondor, F-94010 Creteil, France.
[Decaens, Thomas] INSERM, U955, F-94000 Creteil, France.
[Franco, Dominique] Hop Antoine Beclere, F-92141 Clamart, France.
[Samuel, Didier] Hop Paul Brousse, AP HP, Ctr Hepatobilaire, F-94800 Villejuif, France.
[Samuel, Didier] INSERM, U785, F-94800 Villejuif, France.
[Zucman-Rossi, Jessica] INSERM, U674, F-75010 Paris, France.
[Eils, Roland] Heidelberg Univ, D-69120 Heidelberg, Germany.
[Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69126 Heidelberg, Germany.
[Korshunov, Andrey] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
[Landgraf, Pablo] Univ Dusseldorf, Clin Pediat Oncol Hematol & Immunol, D-40225 Dusseldorf, Germany.
[Lehrach, Hans] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Pfister, Stefan] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany.
[Reifenberger, Guido] Univ Dusseldorf, Inst Neuropathol, D-40001 Dusseldorf, Germany.
[Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
[Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
[von Kalle, Christof] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
[von Kalle, Christof] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany.
[Pederzoli, Paolo] Univ Hosp Trust Verona, Dept Surg, I-37134 Verona, Italy.
[Delledonne, Massimo] Univ Verona, Dept Biotechnol, Funct Genom Ctr, I-37134 Verona, Italy.
[Bardelli, Alberto] Univ Torino, Inst Canc Res & Treatment, Mol Genet Lab, I-10060 Turin, Italy.
[Bardelli, Alberto] FIRC Inst Mol Oncol, I-20139 Milan, Italy.
[Gress, Thomas] Univ Marburg, Dept Gastroenterol Endocrinol Metab & Infectiol, D-35043 Marburg, Germany.
[Klimstra, David] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Nakamura, Yusuke; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Minato Ku, Tokyo 1088639, Japan.
Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
[Wilson, Peter J.; de Sanjose, Silvia] Hosp Llobregat, Inst Catala Oncol IDIBELL, Unit Infect & Canc,CIBER Epidemiol & Salud Publ, Canc Epidemiol Res Programme, Lhospitalet De Llobregat 08907, Spain.
[Aparicio, Samuel] British Columbia Canc Agcy, BC Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
[Easton, Douglas F.] Univ Cambridge, Dept Primary Care & Oncol, Dept Publ Hlth, Cambridge CB1 8RN, England.
[Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Burke, Wylie] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA.
[Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
[Green, Anthony R.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England.
[Hamilton, Stanley R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kallioniemi, Olli P.] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland.
[Ley, Timothy J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Ley, Timothy J.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Wainwright, Brandon J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
RP Hudson, TJ (reprint author), Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
EM tom.hudson@oicr.on.ca
RI Gill, Anthony/D-4215-2015; Guigo, Roderic/D-1303-2010; Lopez-Bigas,
Nuria/F-6193-2011; Hubbard, Tim/C-2567-2008; Chalmers, Don/J-7658-2014;
Valencia, Alfonso/I-3127-2015; Radlwimmer, Bernhard/I-3229-2013; IBIS,
SARCOMAS/O-1893-2015; Giuseppe, Zamboni/A-5991-2016; Hirst,
Martin/B-7684-2016; Quesada, Victor/B-6557-2014; Gardiner,
Brooke/C-7773-2011; Marra, Marco/B-5987-2008; McPherson,
John/D-2633-2017; Bea, Silvia/K-7699-2014; Eils, Roland/B-6121-2009;
Pfister, Stefan/F-6860-2013; Clement, Bruno/E-5546-2016; Bowtell,
David/H-1007-2016; Waddell, Nic/H-4929-2015; Prokhortchouk,
Egor/I-9108-2014; Yu, Jun /D-8569-2015; Grimmond, Sean/J-5304-2016;
Jones, Steven/C-3621-2009; Lopez-Otin, Carlos/C-6657-2013; Pearson,
John/F-2249-2011; scarpa, aldo/K-6832-2016; Gasull, Martina/A-6630-2013;
Heath, Simon/J-4138-2012; Ning, Zemin/D-2411-2013; Brors,
Benedikt/E-5620-2013; Gallinger, Steven/E-4575-2013; Zaridze,
David/K-5605-2013; Kallioniemi, Olli/H-4738-2012; Decaens,
Thomas/L-9483-2013; Tang, Macy/B-9798-2014; deFazio, Anna/D-3939-2013;
de Sanjose Llongueras, Silvia/H-6339-2014; Tsunoda,
Tatsuhiko/K-2061-2014; Estivill, Xavier/A-3125-2013; Stunnenberg,
Hendrik/D-6875-2012; Liu, Edison/C-4141-2008; Speed, Terence
/B-8085-2009; Bader, Gary/C-1176-2009; Caldas, Carlos/A-7543-2008;
Cloonan, Nicole/B-5272-2008; Kallioniemi, Olli/H-5111-2011; Gnaneshan,
Saravanamuttu/D-2305-2012; Yuen, Matthew /E-5621-2011; Estivill,
Xavier/E-2957-2012; Korbel, Jan/G-6470-2012; Piris, Miguel/B-7067-2008;
sander, chris/H-1452-2011; IBSAL, Secretaria/H-3719-2011;
OI Egevad, Lars/0000-0001-8531-222X; Suarez-Puente,
Xose/0000-0001-9525-1483; Yung, Christina/0000-0003-2958-150X;
zucman-rossi, Jessica/0000-0002-5687-0334; Banks,
Rosamonde/0000-0002-0042-8715; Tost, Jorg/0000-0002-2683-0817; Flicek,
Paul/0000-0002-3897-7955; Gill, Anthony/0000-0002-9447-1967; Guigo,
Roderic/0000-0002-5738-4477; Lopez-Bigas, Nuria/0000-0003-4925-8988;
Hubbard, Tim/0000-0002-1767-9318; Chalmers, Don/0000-0002-7925-8818;
Valencia, Alfonso/0000-0002-8937-6789; Radlwimmer,
Bernhard/0000-0002-4553-7800; Giuseppe, Zamboni/0000-0001-7428-4673;
Quesada, Victor/0000-0002-8398-3457; Gardiner,
Brooke/0000-0003-3740-3244; McPherson, John/0000-0001-8049-9347; Sarin,
Rajiv/0000-0002-6405-8282; Bea, Silvia/0000-0001-7192-2385; Hayes, D.
Neil/0000-0001-6203-7771; Ning, Zemin/0000-0003-4359-776X; Eils,
Roland/0000-0002-0034-4036; Pfister, Stefan/0000-0002-5447-5322;
Bowtell, David/0000-0001-9089-7525; Grimmond, Sean/0000-0002-8102-7998;
Lopez-Otin, Carlos/0000-0001-6964-1904; Pearson,
John/0000-0003-0904-4598; scarpa, aldo/0000-0003-1678-739X; Brors,
Benedikt/0000-0001-5940-3101; Kallioniemi, Olli/0000-0002-3231-0332;
deFazio, Anna/0000-0003-0057-4744; Estivill, Xavier/0000-0002-0723-2256;
Speed, Terence /0000-0002-5403-7998; Bader, Gary/0000-0003-0185-8861;
Kallioniemi, Olli/0000-0002-3231-0332; Gnaneshan,
Saravanamuttu/0000-0002-0455-8701; Yuen, Matthew /0000-0002-6773-328X;
Korbel, Jan/0000-0002-2798-3794; Piris, Miguel/0000-0001-5839-3634;
Campo, elias/0000-0001-9850-9793; Brazma, Alvis/0000-0001-5988-7409;
lawlor, Rita/0000-0003-3160-0634; Birney, Ewan/0000-0001-8314-8497;
Martin, Sancha/0000-0001-6213-5259; Biankin, Andrew/0000-0002-0362-5597;
Gonzalez Diaz, Marcos/0000-0001-6637-1072
NR 35
TC 714
Z9 725
U1 15
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 993
EP 998
DI 10.1038/nature08987
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000029
ER
PT J
AU Lenz, G
Staudt, LM
AF Lenz, Georg
Staudt, Louis M.
TI Mechanisms of Disease: Aggressive Lymphomas.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID B-CELL LYMPHOMA; NF-KAPPA-B; CLASS-SWITCH RECOMBINATION; GERMINAL-CENTER
FORMATION; CLASSICAL HODGKIN LYMPHOMA; TUMOR-SUPPRESSOR GENE; SOMATIC
HYPERMUTATION; MOLECULAR DIAGNOSIS; CHROMOSOME BREAKS; BURKITTS-LYMPHOMA
C1 [Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Metab Branch, Bethesda, MD 20892 USA.
[Lenz, Georg] Charite Humboldt Univ, Dept Hematol Oncol, Berlin, Germany.
RP Staudt, LM (reprint author), NCI, Ctr Canc Res, NIH, Metab Branch, Bldg 10,Rm 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
RI Lenz, Georg/I-6844-2012
FU Intramural Research Program; National Cancer Institute; Center for
Cancer Research at the National Institutes of Health; German Research
Foundation
FX Supported by the Intramural Research Program, the National Cancer
Institute, and the Center for Cancer Research at the National Institutes
of Health and a grant from the German Research Foundation ( to Dr.
Lenz).
NR 100
TC 265
Z9 273
U1 1
U2 13
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 15
PY 2010
VL 362
IS 15
BP 1417
EP 1429
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 582XY
UT WOS:000276635300010
PM 20393178
ER
PT J
AU Matthews, JL
Schultz, IR
Easterling, MR
Melnick, RL
AF Matthews, Jessica L.
Schultz, Irvin R.
Easterling, Michael R.
Melnick, Ronald L.
TI Physiologically based pharmacokinetic modeling of dibromoacetic acid in
F344 rats
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Dibromoacetic acid; Glutathione-S-transferase zeta; F344 rats; PBPK
ID GLUTATHIONE-TRANSFERASE-ZETA; SPRAGUE-DAWLEY RATS; DICHLOROACETIC ACID;
DRINKING-WATER; DOSE-RESPONSE; B6C3F1 MICE; CATALYZED BIOTRANSFORMATION;
ORAL BIOAVAILABILITY; URINARY METABOLITES; TYROSINE METABOLISM
AB A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite alpha-halocarboxymethylglutathione (alpha H1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Matthews, Jessica L.; Easterling, Michael R.] SRA Int Inc, Durham, NC 27713 USA.
[Schultz, Irvin R.] Battelle Pacific NW Lab, Sequim, WA 98382 USA.
[Melnick, Ronald L.] NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Matthews, JL (reprint author), SRA Int Inc, 2605 Meridian Pkwy,Suite 200, Durham, NC 27713 USA.
EM Jessica_Matthews@sra.com; irv.schultz@pnl.gov;
Michael_Easterling@sra.com; ron.melnick@gmail.com
RI Matthews, Jessica/D-5478-2014;
OI Matthews, Jessica L./0000-0002-6968-3474
FU National Institutes of Health (NIH), National Institute of Environmental
Health Sciences (NIEHS); National Toxicology Program (NTP); NIEHS
[GS-00E-0003L, HHSN273200700060P]
FX This work was supported (in part) by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS) and the National Toxicology
Program (NTP). The work of J. Matthews was supported by NIEHS contract
#GS-00E-0003L. The work of Dr. Schultz was supported by NIEHS contract
#HHSN273200700060P.
NR 42
TC 2
Z9 2
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 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD APR 15
PY 2010
VL 244
IS 2
BP 196
EP 207
DI 10.1016/j.taap.2009.12.033
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 583HO
UT WOS:000276664800011
PM 20045428
ER
PT J
AU Volkow, ND
Montaner, J
AF Volkow, Nora D.
Montaner, Julio
TI Enhanced HIV Testing, Treatment, and Support for HIV-Infected Substance
Users
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; EPIDEMIC; CARE
C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Montaner, Julio] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Montaner, Julio] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Montaner, Julio] Int AIDS Soc, Geneva, Switzerland.
RP Volkow, ND (reprint author), 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Canadian Institutes of Health Research; NIDA NIH HHS [DP1 DA026182]
NR 10
TC 32
Z9 32
U1 0
U2 4
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 APR 14
PY 2010
VL 303
IS 14
BP 1423
EP 1424
DI 10.1001/jama.2010.421
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 582KX
UT WOS:000276597300029
PM 20388900
ER
PT J
AU Mozhui, K
Karlsson, RM
Kash, TL
Ihne, J
Norcross, M
Patel, S
Farrell, MR
Hill, EE
Graybeal, C
Martin, KP
Camp, M
Fitzgerald, PJ
Ciobanu, DC
Sprengel, R
Mishina, M
Wellman, CL
Winder, DG
Williams, RW
Holmes, A
AF Mozhui, Khyobeni
Karlsson, Rose-Marie
Kash, Thomas L.
Ihne, Jessica
Norcross, Maxine
Patel, Sachin
Farrell, Mollee R.
Hill, Elizabeth E.
Graybeal, Carolyn
Martin, Kathryn P.
Camp, Marguerite
Fitzgerald, Paul J.
Ciobanu, Daniel C.
Sprengel, Rolf
Mishina, Masayoshi
Wellman, Cara L.
Winder, Danny G.
Williams, Robert W.
Holmes, Andrew
TI Strain Differences in Stress Responsivity Are Associated with Divergent
Amygdala Gene Expression and Glutamate-Mediated Neuronal Excitability
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CHRONIC MILD STRESS; REPEATED MATERNAL SEPARATION; DEPRESSION-LIKE
BEHAVIOR; INBRED MOUSE STRAINS; ANIMAL-MODEL; MICE LACKING; SEROTONIN
TRANSPORTER; BASOLATERAL AMYGDALA; VISUAL-CORTEX; MUTANT MICE
AB Stress is a major risk factor for numerous neuropsychiatric diseases. However, susceptibility to stress and the qualitative nature of stress effects on behavior differ markedly among individuals. This is partly because of the moderating influence of genetic factors. Inbred mouse strains provide a relatively stable and restricted range of genetic and environmental variability that is valuable for disentangling gene-stress interactions. Here, we screened a panel of inbred strains for anxiety- and depression-related phenotypes at baseline (trait) and after exposure to repeated restraint. Two strains, DBA/2J and C57BL/6J, differed in trait and restraint-induced anxiety-related behavior (dark/light exploration, elevated plus maze). Gene expression analysis of amygdala, medial prefrontal cortex, and hippocampus revealed divergent expression in DBA/2J and C57BL/6J both at baseline and after repeated restraint. Restraint produced strain-dependent expression alterations in various genes including glutamate receptors (e.g., Grin1, Grik1). To elucidate neuronal correlates of these strain differences, we performed ex vivo analysis of glutamate excitatory neurotransmission in amygdala principal neurons. Repeated restraint augmented amygdala excitatory postsynaptic signaling and altered metaplasticity (temporal summation of NMDA receptor currents) in DBA/2J but not C57BL/6J. Furthermore, we found that the C57BL/6J-like changes in anxiety-related behavior after restraint were absent in null mutants lacking the modulatory NMDA receptor subunit Grin2a, but not the AMPA receptor subunit Gria1. Grin2a null mutants exhibited significant (similar to 30%) loss of dendritic spines on amygdala principal neurons under nonrestraint conditions. Collectively, our data support a model in which genetic variation in glutamatergic neuroplasticity in corticolimbic circuitry underlies phenotypic variation in responsivity to stress.
C1 [Karlsson, Rose-Marie; Ihne, Jessica; Norcross, Maxine; Graybeal, Carolyn; Martin, Kathryn P.; Camp, Marguerite; Fitzgerald, Paul J.; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Mozhui, Khyobeni; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
[Kash, Thomas L.; Winder, Danny G.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA.
[Patel, Sachin] Vanderbilt Univ, Dept Psychiat, Sch Med, Nashville, TN 37232 USA.
[Farrell, Mollee R.; Hill, Elizabeth E.; Wellman, Cara L.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Ciobanu, Daniel C.] Univ Nebraska, Dept Anim Sci, Lincoln, NE 68583 USA.
[Sprengel, Rolf] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
[Mishina, Masayoshi] Univ Tokyo, Grad Sch Med, Dept Mol Neurobiol & Pharmacol, Tokyo 1130033, Japan.
RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM holmesan@mail.nih.gov
RI Patel, Sachin/E-5608-2012; Kash, Thomas/G-9625-2013; Winder,
Danny/H-4857-2013;
OI Reed, Jessica/0000-0003-0550-7284; Williams, Robert/0000-0001-8924-4447
FU National Institute on Alcohol Abuse and Alcoholism [Z01-AA000411];
National Institute of Mental Health [Z01-MH002784]; National Institute
on Drug Abuse; NIMH; NIAAA HPG [P20-DA 21131]; National Center for
Research Resources Biomedical Informatics Research Network [U24
RR021760]; NIAAA Integrative Neuroscience Initiative on Alcoholism
[U01AA13499, U24AA13513]
FX This work was supported by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA; Z01-AA000411) and National Institute of Mental Health
(NIMH; Z01-MH002784) Intramural Research Programs, and by National
Institute on Drug Abuse, NIMH, and NIAAA HPG Grant P20-DA 21131,
National Center for Research Resources Biomedical Informatics Research
Network Grant U24 RR021760, and NIAAA Integrative Neuroscience
Initiative on Alcoholism Grants U01AA13499 and U24AA13513. We are
grateful to Dr. Heather Cameron for help with radioimmunoassay.
NR 68
TC 98
Z9 99
U1 2
U2 10
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 APR 14
PY 2010
VL 30
IS 15
BP 5357
EP 5367
DI 10.1523/JNEUROSCI.5017-09.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 583NS
UT WOS:000276685100023
PM 20392957
ER
EF