FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Singh, A
Ling, GY
Suhasini, AN
Zhang, P
Yamamoto, M
Navas-Acien, A
Cosgrove, G
Tuder, RM
Kensler, TW
Watson, WH
Biswal, S
AF Singh, Anju
Ling, Guoyu
Suhasini, Avvaru N.
Zhang, Ping
Yamamoto, Masayuki
Navas-Acien, Ana
Cosgrove, Gregory
Tuder, Rubin M.
Kensler, Thomas W.
Watson, Walter H.
Biswal, Shyam
TI Nrf2-dependent sulfiredoxin-1 expression protects against cigarette
smoke-induced oxidative stress in lungs
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Srx1; Nrf2; Oxidative stress; Antioxidant response element; Chronic
obstructive pulmonary disease; Emphysema; Free radicals
ID OBSTRUCTIVE PULMONARY-DISEASE; CYSTEINE-SULFINIC ACID; NRF2 ENHANCES
SUSCEPTIBILITY; ANTIOXIDANT RESPONSE ELEMENT; PLANAR AROMATIC-COMPOUNDS;
YA SUBUNIT GENE; TRANSCRIPTION FACTORS; INDUCIBLE EXPRESSION; DIESEL
EXHAUST; CELL-SURVIVAL
AB Oxidative stress results in protein oxidation and is involved in the pathogenesis of lung diseases such as chronic obstructive pulmonary disorder (COPD). Sulfiredoxin-1 (Srx1) catalyzes the reduction of cysteine sulfinic acid to sulfenic acid in oxidized proteins and protects them from inactivation. This study examined the mechanism of transcriptional regulation of Srx1 and its possible protective role during oxidative stress associated with COPD. Nrf2, a transcription factor known to influence susceptibility to pulmonary diseases, upregulates Srx1 expression during oxidative stress caused by cigarette smoke exposure in the lungs of mice. Disruption of Nrf2 signaling by genetic knockout in mice or RNAi in cells downregulated the expression of Srx1. In silico analysis of the 5'-promoter-flanking region of Srx1 identified multiple antioxidant-response elements (AREs) that are highly conserved. Reporter and chromatin-immunoprecipitation assays demonstrated that ARE1 at -228 is critical for the Nrf2-mediated response. Attenuation of Srx1 expression with RNAi potentiated the toxicity of hydrogen peroxide (H(2)O(2)), whereas overexpression of Srx1 protected against H(2)O(2)-mediated cell death in vitro. Immunoblot analysis revealed dramatic decreases in Srx1 expression in lungs from patients with COPD relative to nonemphysematous lungs together with a decline in Nrf2 protein. Thus, Srx1, a key Nrf2-regulated gene, contributes to protection against oxidative injury in the lung. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Singh, Anju; Ling, Guoyu; Zhang, Ping; Yamamoto, Masayuki; Navas-Acien, Ana; Kensler, Thomas W.; Watson, Walter H.; Biswal, Shyam] Johns Hopkins Univ, Dept Environm Hlth Sci, John Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Suhasini, Avvaru N.] NIA, NIH, Baltimore, MD 21224 USA.
[Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan.
[Yamamoto, Masayuki] ERATO, Environm Response Project, Aoba Ku, Sendai, Miyagi 9808575, Japan.
[Cosgrove, Gregory] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Cosgrove, Gregory; Tuder, Rubin M.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA.
[Kensler, Thomas W.; Biswal, Shyam] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21205 USA.
RP Biswal, S (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, John Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM sbiswal@jhsph.edu
RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014
OI Kensler, Thomas/0000-0002-6676-261X
FU NIH [R01 HL081205, P50 HL084945, P50 CA058184, P50 ES015903,
P30ES03819]; Flight Attendant Medical Research Institute
FX This work was supported by NIH Grants R01 HL081205 (S.B.), SCCOR P50
HL084945, P50 CA058184, P50 ES015903 and P30ES03819 and a Young Clinical
Innovator Award (S.B., AN) and a Young Clinical Scientist Award to Anju
Singh from the Flight Attendant Medical Research Institute. We thank
james Watkins III for providing frozen COPD tissues.
NR 53
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U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD FEB 1
PY 2009
VL 46
IS 3
BP 376
EP 386
DI 10.1016/j.freeradbiomed.2008.10.026
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 395LJ
UT WOS:000262525300006
PM 19027064
ER
PT J
AU Flores, J
AF Flores, Jorge
TI Seeking new pathways for HIV vaccine discovery
SO FUTURE MICROBIOLOGY
LA English
DT Editorial Material
ID INFECTION; GENOME; TRIAL; HOSTS
C1 NIAID, Vaccine Res Program, Div AIDS, NIH, Bethesda, MD 20892 USA.
RP Flores, J (reprint author), NIAID, Vaccine Res Program, Div AIDS, NIH, Bethesda, MD 20892 USA.
EM jflores@niad.nih.gov
NR 18
TC 5
Z9 5
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0913
J9 FUTURE MICROBIOL
JI Future Microbiol.
PD FEB
PY 2009
VL 4
IS 1
BP 1
EP 7
DI 10.2217/17460913.4.1.1
PG 7
WC Microbiology
SC Microbiology
GA 412VO
UT WOS:000263752500001
PM 19207094
ER
PT J
AU Everhart, JE
Ruhl, CE
AF Everhart, James E.
Ruhl, Constance E.
TI Burden of Digestive Diseases in the United States Part I: Overall and
Upper Gastrointestinal Diseases
SO GASTROENTEROLOGY
LA English
DT Review
C1 [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
Social & Sci Syst Inc, Silver Spring, MD USA.
RP Everhart, JE (reprint author), NIDDK, Div Digest Dis & Nutr, 2 Democracy Plaza,Room 655,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA.
EM JE17G@NIH.GOV
FU HHS [N267200612918C, N267200700001G]
FX Supported by HHS contracts N267200612918C and N267200700001G.
NR 11
TC 163
Z9 172
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD FEB
PY 2009
VL 136
IS 2
BP 376
EP 386
DI 10.1053/j.gastro.2008.12.015
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 401UK
UT WOS:000262967700005
PM 19124023
ER
PT J
AU Ruhl, CE
Everhart, JE
AF Ruhl, Constance E.
Everhart, James E.
TI Elevated Serum Alanine Aminotransferase and gamma-Glutamyltransferase
and Mortality in the United States Population
SO GASTROENTEROLOGY
LA English
DT Article
ID ALL-CAUSE MORTALITY; MIDDLE-AGED MEN; C-REACTIVE PROTEIN; METABOLIC
SYNDROME; RISK-FACTORS; FOLLOW-UP; CARDIOVASCULAR-DISEASE; FATTY LIVER;
CONSTRUCTION WORKERS; CAFFEINE CONSUMPTION
AB Background & Aims: Elevated serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) activities are markers of liver injury, but may also be associated with other diseases and death. In a prospective, national, population-based sample, we examined whether elevated ALT and GGT were associated with increased risk of all-cause and disease-specific mortality. Methods: Death certificate-based 12-year mortality was analyzed among 14,950 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, who were negative for markers of viral hepatitis B and C. Abnormal ALT was defined as > 30 U/L in men or > 19 U/L in women, and abnormal GGT as > 51 U/L in men or > 33 U/L in women. Results: Cumulative mortality was 13.9% from all causes, including 4.2% from cardiovascular disease, 4.2% from neoplasms, 0.44% from diabetes, and 0.13% from liver disease. In multivariate-adjusted analyses, elevated ALT was not associated with all-cause mortality (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.88-1.6). ALT elevation was associated with deaths from liver disease (HR, 8.2; 95% CI, 2.1-31.9), but not from cardiovascular disease (HR, 0.90; 95% CI, 0.56-1.4), neoplasms (HR, 1.0; 95% Cl, 0.65-1.5), or diabetes (HR, 2.4; 95% CI, 0.65-9.1). All-cause mortality increased with elevated GGT (HR, 1.5; 95% CI, 1.2-1.8), as did mortality from liver disease (HR, 13.0; 95% CI, 2.4-71.5), neoplasms (HR, 1.5; 95% CI, 1.01-2.2), and diabetes (HR, 3.3; 95% CI, 1.4-7.6), but not from cardiovascular disease (HR, 1.3; 95% Cl, 0.80-2.0). Conclusions: In the US population, elevated GGT was associated with mortality from all causes, liver disease, cancer, and diabetes, while ALT was associated only with liver disease mortality.
C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
[Everhart, James E.] NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM cruhl@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN267200700001G]
FX Supported by a contract from the National Institute of Diabetes and
Digestive and Kidney Diseases (HHSN267200700001G).
NR 61
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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 FEB
PY 2009
VL 136
IS 2
BP 477
EP 485
DI 10.1053/j.gastro.2008.10.052
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 401UK
UT WOS:000262967700019
PM 19100265
ER
PT J
AU Kuzin, A
Kundu, M
Ekatomatis, A
Brody, T
Odenwald, WF
AF Kuzin, Alexander
Kundu, Mukta
Ekatomatis, Antonios
Brody, Thomas
Odenwald, Ward F.
TI Conserved sequence block clustering and flanking inter-cluster
flexibility delineate enhancers that regulate nerfin-1 expression during
Drosophila CNS development
SO GENE EXPRESSION PATTERNS
LA English
DT Article
DE Enhancers; Drosophila; Nervous system development; EvoPrinter;
phylogenetic footprinting; Nerfin-1; Transcription factor; Embryonic
expression; Larval expression
ID DEVELOPING NERVOUS-SYSTEM; FINGER TRANSCRIPTION FACTOR; COMPARATIVE
GENOMICS; ELEMENT VECTORS; CELL FATE; GENES; IDENTIFICATION; KRUPPEL;
DNA; SPECIFICITY
AB We have identified clusters of conserved sequences constituting discrete modular enhancers within the Drosophila nerfin-1 locus. nerfin-1 encodes a Zn-finger transcription factor that directs pioneer interneuron axon guidance. nerfin-1 mRNA is detected in many early delaminating neuroblasts, ganglion mother cells and transiently in nascent neurons. The comparative genomics analysis program EvoPrinter revealed conserved sequence blocks both upstream and downstream of the transcribed region. By using the aligning regions of different drosophilids as the reference DNA, EvoPrinter detects Sequence length flexibility between clusters of conserved sequences and thus facilitates differentiation between closely associated modular enhancers. Expression analysis of enhancer-reporter transgenes identified enhancers that drive expression in different regions of the developing embryonic and adult nervous system, including subsets of embryonic CNS neuroblasts, GMCs, neurons and PNS neurons. In Summary, EvoPrinter facilitates the discovery and analysis of enhancers that control crucial aspects of nerfin-1 expression. Published by Elsevier B.V.
C1 [Kuzin, Alexander; Kundu, Mukta; Ekatomatis, Antonios; Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
RP Kuzin, A (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM Alex.Kuzin@ninds.nih.gov; ward@codon.nih.gov
FU NIH; NINDS
FX We thank Jermaine Ross and members of the NINDS central sequencing
facility for their technical support and acknowledge the editorial
expertise of Judith Brody. This research was supported by the Intramural
Research Program of the NIH, NINDS.
NR 35
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-133X
J9 GENE EXPR PATTERNS
JI Gene Expr. Patterns
PD FEB
PY 2009
VL 9
IS 2
BP 65
EP 72
DI 10.1016/j.gep.2008.10.005
PG 8
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 405IW
UT WOS:000263217500001
PM 19056518
ER
PT J
AU Shimada, M
Wang, HB
Kondo, A
Xu, XP
Yoshida, A
Shinoda, K
Ura, T
Mizuguchi, H
Klinman, D
Luo, JL
Bai, H
Okuda, K
AF Shimada, M.
Wang, H. -B
Kondo, A.
Xu, X. -P
Yoshida, A.
Shinoda, K.
Ura, T.
Mizuguchi, H.
Klinman, D.
Luo, J. -L
Bai, H.
Okuda, K.
TI Effect of therapeutic immunization using Ad5/35 and MVA vectors on SIV
infection of rhesus monkeys undergoing antiretroviral therapy
SO GENE THERAPY
LA English
DT Article
DE vaccine; virus vector; SIV; monkey model; therapy
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEMORY T-CELLS; TREATMENT INTERRUPTIONS;
PROTECTIVE IMMUNITY; VIRAL SUPPRESSION; HIV-1 INFECTION; VACCINE
VECTORS; SIMIAN AIDS; VIREMIA; REPLICATION
AB Antiretroviral therapy (ART) effectively slows the progression of AIDS. However, drug resistance and/or toxicity can limit the utility of ART in many patients. In this study, we assessed whether a viral vector-based vaccine can be used as a therapeutic vaccine in simian immunodeficiency virus (SIV)-infected monkeys. The effect of vaccinating SIVmac239-infected rhesus monkeys with an SIV gag and gp120-expressing adenovirus (Ad) vector vaccine and a modified vaccinia Ankara (MVA) vaccine was explored while being treated with ART. Rhesus monkeys were intravenously infected with 10 and 1000 TCID(50) (50% tissue culture infectious dose) of SIVmac239. Two months after SIV infection, the monkeys received a 4-month treatment with ART. Some of the monkeys were immunized with adenovirus-based vaccine and MVA-based vaccine with 2 months interval during ART. Viral load, CD4 count and SIV-specific immune responses were observed for 7 months after interruption of ART. The vaccinated animals had higher (i) CD4 counts, (ii) SIV-specific cell-mediated immune responses and (iii) anti-SIV-neutralizing antibody (Ab) titers than monkeys treated with ART alone. More importantly, the vaccination significantly reduced the SIV RNA load from animals infected with a low dose of SIV (10 TCID(50)). The anti-SIV cell-mediated and humoral responses induced by the vaccination was inversely correlated with a reduction in SIV viral load and positively correlated with an increase in CD4(+) T cell counts. These results suggest that vaccination can improve antiviral cell-mediated and humoral immunity, which may contribute to controlling viral replication.
C1 [Shimada, M.; Kondo, A.; Yoshida, A.; Shinoda, K.; Ura, T.; Okuda, K.] Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan.
[Wang, H. -B; Xu, X. -P; Luo, J. -L; Bai, H.] Hisun Pharmaceut Co, Taizhou, Zhejiang, Peoples R China.
[Mizuguchi, H.] Natl Inst Biomed Innovat, Lab Gene Transfer & Regulat, Osaka, Japan.
[Klinman, D.] NCI, NIH, Frederick, MD 21701 USA.
RP Shimada, M (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM mshimada@yokohama-cu.ac.jp
FU Ministry of Education, Science, Sports and Culture of Japan; Strategic
Research Project of Yokohama City University Japan; Research Foundation
for Advanced Medical Research Center; Japanese National Institute of
Biomedical Innovation [05-1]
FX We thank NIH Tetramer Core Facility (Atlanta, GA, USA) for the tetramer;
Gilead Sciences Inc. (Foster City, CA, USA) for
(R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA); Drs Chuan Qin, Hong
Gao and Li-San Pan (Institute of Laboratory Animal Science, Chinese
Academy of Medical Sciences) for animal care and treatment. This work
was partially supported by a Grant-in-Aid from the Ministry of
Education, Science, Sports and Culture of Japan; a grant for the
Strategic Research Project of Yokohama City University, Japan; a grant
from the Research Foundation for Advanced Medical Research Center and a
grant from the Japanese National Institute of Biomedical Innovation (No.
05-1).
NR 46
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U1 0
U2 0
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 FEB
PY 2009
VL 16
IS 2
BP 218
EP 228
DI 10.1038/gt.2008.152
PG 11
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 414VH
UT WOS:000263892800007
PM 18923453
ER
PT J
AU Crusio, WE
Goldowitz, D
Holmes, A
Wolfer, D
AF Crusio, W. E.
Goldowitz, D.
Holmes, A.
Wolfer, D.
TI Standards for the publication of mouse mutant studies
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
ID C57BL/6J INBRED MICE; NEUROANATOMICAL DIVERGENCE; KNOCKOUT MICE; STRAIN
129; GENE; SUBSTRAINS; BEHAVIOR; NOMENCLATURE; SEROTONIN
C1 [Crusio, W. E.] Univ Bordeaux, Ctr Neurosci Integrat & Cognit, CNRS UMR 5228, F-33405 Talence, France.
[Goldowitz, D.] Univ British Columbia, Ctr Mol Med & Therapeut, Child & Family Res Inst, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada.
[Holmes, A.] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA.
[Wolfer, D.] Univ Zurich, Inst Anat, Zurich, Switzerland.
[Wolfer, D.] ETH, Inst Human Movement Sci & Sport, Zurich, Switzerland.
RP Crusio, WE (reprint author), Univ Bordeaux, Ctr Neurosci Integrat & Cognit, CNRS UMR 5228, Bat B2,Ave Fac, F-33405 Talence, France.
EM wim_crusio@yahoo.com
RI Crusio, Wim/A-7070-2008; Wolfer, David/B-3293-2016
OI Crusio, Wim/0000-0001-6638-202X; Wolfer, David/0000-0002-5957-1401
NR 25
TC 59
Z9 59
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD FEB
PY 2009
VL 8
IS 1
BP 1
EP 4
DI 10.1111/j.1601-183X.2008.00438.x
PG 4
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 400SD
UT WOS:000262888000001
PM 18778401
ER
PT J
AU Enoch, MA
Waheed, JF
Harris, CR
Albaugh, B
Goldman, D
AF Enoch, M. -A.
Waheed, J. F.
Harris, C. R.
Albaugh, B.
Goldman, D.
TI COMT Val158Met and cognition: main effects and interaction with
educational attainment
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Anxiety; attention; COMT Val158Met; education; long-term memory;
resilience; WAIS-R; working memory
ID CATECHOL-O-METHYLTRANSFERASE; VAL(158)MET GENOTYPE; PREFRONTAL CORTEX;
EXECUTIVE FUNCTION; POLYMORPHISM; GENE; ANXIETY; SCHIZOPHRENIA;
ASSOCIATION; PERFORMANCE
AB Studies in children have shown that the genetic influence on cognition is positively correlated with socioeconomic status. Catechol-O-methyltransferase (COMT) Val158Met, a common, functional polymorphism, has been implicated in executive cognition and working memory. Imaging studies have shown that the variant Met allele is associated with more efficient prefrontal cortical processing and better attention but also emotional vulnerability to stress. We hypothesized that COMT Val158Met genotype would interact with years of education (yrs ed), one indicator of socioeconomic adversity, to predict cognitive task performance. We therefore administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to 328 community-derived, genotyped, Plains American Indians (mean yrs ed = 12; range = 5-18). We found significant genotypic effects on WAIS-R measures of long-term memory, working memory and attention. The Met allele was associated with improved performance in the Information and Picture Completion subscales; Met/Met homozygotes performed the best. COMT genotype interacted with yrs ed to influence Information and Block Design scores: Met allele carriers' scores improved markedly with increasing yrs ed, whereas the scores of Val/Val individuals were only marginally influenced by yrs ed. There was a crossover of effects at 11-12 yrs ed: in the less educated group, Met allele carriers actually performed worse than Val/Val individuals perhaps because of emotional vulnerability to educational adversity, but in the better educated group, Met allele carriers excelled. Our study in Plains American Indians has shown that COMT Val158Met influences several aspects of cognition and some of its effects are moderated by educational adversity.
C1 [Enoch, M. -A.; Waheed, J. F.; Harris, C. R.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Albaugh, B.] Ctr Human Behav Studies Inc, Weatherford, OK USA.
RP Enoch, MA (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA.
EM maenoch@niaaa.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institute on Alcohol Abuse and Alcoholism; NIH; Office of
Research on Minority Health
FX We thank Pei-Hong Shen and Longina Akhtar for technical assistance. This
research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH and in part by
the Office of Research on Minority Health.
NR 35
TC 24
Z9 25
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD FEB
PY 2009
VL 8
IS 1
BP 36
EP 42
DI 10.1111/j.1601-183X.2008.00441.x
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 400SD
UT WOS:000262888000005
PM 19076243
ER
PT J
AU Nyholt, DR
Gillespie, NG
Merikangas, KR
Treloar, SA
Martin, NG
Montgomery, GW
AF Nyholt, Dale R.
Gillespie, Nathan G.
Merikangas, Kathleen R.
Treloar, Susan A.
Martin, Nicholas G.
Montgomery, Grant W.
TI Common Genetic Influences Underlie Comorbidity of Migraine and
Endometriosis
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE heritability; headache; women; hormones; pain; comorbid
ID TENSION-TYPE HEADACHE; GENERAL-POPULATION; ORAL-CONTRACEPTIVES;
MENSTRUAL MIGRAINE; FAMILIAL RISK; DOUBLE-BLIND; LATENT CLASS; TWIN
SAMPLE; LIFE-STYLE; PREVALENCE
AB We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12-2.21, P = 0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2) = 0.17, 95% CI: 0.08-0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes. Genet. Epidemiol. 33:105-113, 2009. (C) 2008 Wiley-Liss, Inc.
C1 [Nyholt, Dale R.] PO Royal Brisbane Hosp, Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia.
[Gillespie, Nathan G.] VCU, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia.
RP Nyholt, DR (reprint author), PO Royal Brisbane Hosp, Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia.
EM daleN@qimr.edu.au
RI Nyholt, Dale/C-8384-2013; Gillespie, Nathan/D-6029-2013; Montgomery,
Grant/B-7148-2008;
OI Montgomery, Grant/0000-0002-4140-8139; Martin,
Nicholas/0000-0003-4069-8020
FU NHMRC RD Wright [339462]; NHMRC [4339430]; Mayne Bequest Fund (The
University of Queensland, Brisbane, Australia); Australian
Gynaecological Endoscopy Society; Cooperative Research Centre for
Discovery of Genes for Common Human Diseases (CRC); Cerylid Biosciences
(Melbourne); Neville and Shirley Hawkins; Western Australian
Endometriosis Support Association; Endometriosis Association
FX We thank Dr Daniel T. O'Connor for assistance with recruitment and
confirmation of endometriosis diagnoses, Barbara Haddon for coordinating
the endometriosis study recruitment and Clare Redfern for coordinating
the collection of migraine data in endometriosis families. DRN is
supported by an NHMRC RD Wright Fellowship (#339462). This research was
supported in part by NHMRC Project Grant (4339430). The 1993-1994
Gynaecological Health Study was funded by the Mayne Bequest Fund (The
University of Queensland, Brisbane, Australia) and the Australian
Gynaecological Endoscopy Society. The Australian endometriosis study
recruitment was funded by Cooperative Research Centre for Discovery of
Genes for Common Human Diseases (CRC), by Cerylid Biosciences
(Melbourne), and by donations from Neville and Shirley Hawkins, the
Western Australian Endometriosis Support Association and the
Endometriosis Association.
NR 79
TC 15
Z9 15
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 FEB
PY 2009
VL 33
IS 2
BP 105
EP 113
DI 10.1002/gepi.20361
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 401UN
UT WOS:000262968000002
PM 18636479
ER
PT J
AU Vermeulen, SH
Shi, M
Weinberg, CR
Umbach, DM
AF Vermeulen, Sita H.
Shi, Min
Weinberg, Clarice R.
Umbach, David M.
TI A Hybrid Design: Case-Parent Triads Supplemented by Control-Mother Dyads
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE genetic relative risk; maternal effect; single nucleotide polymorphism
(SNP); association studies; family-based design; population-based
design; Poisson regression; early-onset disease
ID TRANSMISSION DISEQUILIBRIUM TEST; ASSOCIATION; DISEASE; GENES; RISK
AB Hybrid designs arose from an effort to combine the benefits of family-based and population-based study designs. A recently proposed hybrid approach augments case-parent triads with population-based control-parent triads, genotyping everyone except the control offspring. Including parents of controls substantially improves statistical efficiency for testing and estimating both offspring and maternal genetic relative risk parameters relative to using case-parent triads alone. Moreover, it allows testing of required assumptions. Nevertheless, control fathers can be hard to recruit, whereas control offspring and their mothers may be readily available. Consequently, we propose an alternative hybrid design where offspring-mother pairs, instead of parents, serve as population-based controls. We compare the power of our proposed method with several competitors and show that it performs well in various scenarios, though it is slightly less powerful than the hybrid design that uses control parents. We describe approaches for checking whether population stratification will bias inferences that use controls and whether the mating-symmetry assumption holds. Surprisingly, if mating symmetry is violated, even though mating-type parameters cannot be directly estimated using control-mother dyads alone, and maternal effects cannot be estimated using case-parent triads alone, combining both sources of data allows estimation of all the parameters. This hybrid design can also be used to study environmental influences on disease risk and gene-by-environment interactions. Genet. Epidemiol. 33:136-144, 2009. Published 2008 Wiley-Liss, Inc.
C1 [Shi, Min; Weinberg, Clarice R.; Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol, Biostat & HTA, NL-6525 ED Nijmegen, Netherlands.
RP Umbach, DM (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA.
EM umbach@niehs.nih.gov
RI Vermeulen, H.H.M./L-4716-2015
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [NIH Z01-ES040007]; Ter Meulen Fund
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (NIH
Z01-ES040007) and by the Ter Meulen Fund. We thank Drs. Abee Boyles and
Gregg Dinse for their helpful comments.
NR 13
TC 13
Z9 15
U1 0
U2 1
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 FEB
PY 2009
VL 33
IS 2
BP 136
EP 144
DI 10.1002/gepi.20365
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 401UN
UT WOS:000262968000005
PM 18759250
ER
PT J
AU Sidransky, E
Pastores, GM
Mori, M
AF Sidransky, Ellen
Pastores, Gregory M.
Mori, Motomi
TI Dosing enzyme replacement therapy for Gaucher disease: older, but are we
wiser?
SO GENETICS IN MEDICINE
LA English
DT Editorial Material
C1 [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Pastores, Gregory M.] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA.
[Pastores, Gregory M.] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
[Mori, Motomi] Oregon Hlth & Sci Univ, OHSU Canc Inst, Portland, OR 97201 USA.
[Mori, Motomi] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room IA213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999]
NR 0
TC 9
Z9 9
U1 0
U2 0
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 FEB
PY 2009
VL 11
IS 2
BP 90
EP 91
DI 10.1097/GIM.0b013e3181928f6a
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 411QB
UT WOS:000263663300004
PM 19265747
ER
PT J
AU Persaud-Sawin, DA
Banach, L
Harry, GJ
AF Persaud-Sawin, Dixie-Ann
Banach, Lynna
Harry, Gaylla Jean
TI Raft Aggregation with Specific Receptor Recruitment Is Required for
Microglial Phagocytosis of A beta(42)
SO GLIA
LA English
DT Article
DE microglia; phagocytosis; rafts; CD36
ID AMYLOID-BETA-PEPTIDE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TRAUMATIC
BRAIN-INJURY; GPI-ANCHORED PROTEINS; RED-BLOOD-CELLS;
ALZHEIMERS-DISEASE; LIPID RAFTS; SCAVENGER RECEPTOR; REGGIE/FLOTILLIN
PROTEINS; MACROPHAGE PHAGOCYTOSIS
AB Microglial phagocytosis contributes to the maintenance of brain homeostasis. Mechanisms involved, however, remain unclear. Using A beta 42 solely as a stimulant, we provide novel insight into regulation of microglial phagocytosis by rafts. We demonstrate the existence of an A beta 42 threshold level of 250 pg/mL, above which microglial phagocytic function is impaired. Low levels of A beta 42 facilitate fluorescent bead uptake, whereas phagocytosis is inhibited when A beta 42 accumulates. We also show that region-specific raft clustering occurs before microglial phagocytosis. Low A beta 42 levels stimulated this type of raft aggregation, but high A beta 42 levels inhibited it. Additionally, treatment with high A beta 42 concentrations caused a redistribution of the raft structural. protein flotillin1 from low to higher density fractions along a sucrose gradient. This suggests a loss of raft structural integrity. Certain non-steroidal anti-inflammatory drugs, e.g., the cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs, celecoxib, raise A beta 42 levels. We demonstrated that prolonged celecoxib exposure can disrupt rafts in a manner similar to that seen in an elevated A beta 42 environment: abnormal raft aggregation and Flot1 distribution. This resulted in aberrant receptor recruitment to rafts and impaired receptor-mediated phagocytosis by microglial cells. Specifically, recruitment of the scavenger receptor CD36 to rafts during active phagocytosis was affected. Thus, we propose that maintaining raft integrity is crucial for determining microglial phagocytic outcomes and disease progression. (C) 2008 Wiley-Liss, Inc.
C1 [Persaud-Sawin, Dixie-Ann] NIEHS, Neurobiol Lab, Neurotoxicol Grp, NIH, Res Triangle Pk, NC 27709 USA.
RP Persaud-Sawin, DA (reprint author), NIEHS, Neurobiol Lab, Neurotoxicol Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM sawind@niehs.nih.gov
FU Division of Intramural Research of NIEHS (NIH) [1Z01ES101623-05]; NTEHS
Chemistry Contract [10015-42-05]
FX Grant sponsor: Division of Intramural Research of NIEHS (NIH); Grant
number: #1Z01ES101623-05; Grant sponsor: NTEHS Chemistry Contract; Grant
number: #10015-42-05.
NR 100
TC 11
Z9 12
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-1491
J9 GLIA
JI Glia
PD FEB
PY 2009
VL 57
IS 3
BP 320
EP 335
DI 10.1002/glia.20759
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 392BF
UT WOS:000262277200008
PM 18756527
ER
PT J
AU Hagen, KGT
Zhang, LP
Tian, E
Zhang, Y
AF Hagen, Kelly G. Ten
Zhang, Liping
Tian, E.
Zhang, Ying
TI Glycobiology on the fly: Developmental and mechanistic insights from
Drosophila
SO GLYCOBIOLOGY
LA English
DT Review
ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; HEPARAN-SULFATE
PROTEOGLYCANS; THROMBOSPONDIN TYPE-1 REPEATS; CAENORHABDITIS-ELEGANS;
PROTEIN O-FUCOSYL-TRANSFERASE-1; FUNCTIONAL-CHARACTERIZATION;
UDP-GALNAC; GLYCOSPHINGOLIPID BIOSYNTHESIS; LIGAND-BINDING; MODIFIES
NOTCH
AB Drosophila melanogaster offers many unique advantages for deciphering the complexities of glycan biosynthesis and function. The completion of the Drosophila genome sequencing project as well as the comprehensive catalogue of existing mutations and phenotypes have lead to a prolific database where many of the genes involved in glycan synthesis, assembly, modification, and recognition have been identified and characterized. Recent biochemical and molecular studies have elucidated the structure of the glycans present in Drosophila. Powerful genetic approaches have uncovered a number of critical biological roles for glycans during development that impact on our understanding of their function during mammalian development. Here, we summarize key recent findings and provide evidence for the usefulness of this model organism in unraveling the complexities of glycobiology across many species.
C1 [Hagen, Kelly G. Ten; Zhang, Liping; Tian, E.] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA.
[Zhang, Ying] Univ Virginia, Old Med Sch, Dept Neurol, Charlottesville, VA 22903 USA.
RP Hagen, KGT (reprint author), NIDCR, Dev Glycobiol Unit, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM Kelly.Tenhagen@nih.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health
FX We would like to thank the many members of the community who have
contributed to the work mentioned herein. We would like to thank Drs.
Lawrence A. Tabak, Jaya Raman, Yu Guan, and Hazuki Miwa for carefully
reading this manuscript. This research was supported by the Intramural
Research Program of the National Institute of Dental and Craniofacial
Research, National Institutes of Health.
NR 91
TC 2
Z9 2
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD FEB
PY 2009
VL 19
IS 2
BP 102
EP 111
DI 10.1093/glycob/cwn096
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 388CD
UT WOS:000261997000001
ER
PT J
AU Wentzensen, N
Sherman, ME
Schiffman, M
Wang, SS
AF Wentzensen, Nicolas
Sherman, Mark E.
Schiffman, Mark
Wang, Sophia S.
TI Utility of methylation markers in cervical cancer early detection:
Appraisal of the state-of-the-science
SO GYNECOLOGIC ONCOLOGY
LA English
DT Review
DE Cervical cancer; Biomarker; Methylation; HPV; CIN
ID HUMAN-PAPILLOMAVIRUS DNA; TUMOR-SUPPRESSOR GENES; PROMOTER
HYPERMETHYLATION; ABERRANT METHYLATION; PROTEIN EXPRESSION; HUMAN
MALIGNANCIES; P16 METHYLATION; UTERINE CERVIX; CELL-LINES; NEOPLASIA
AB Objective. We wanted to identify the most promising methylation marker candidates for cervical cancer early detection.
Methods. A systematic literature review was performed in Medline and weighted average frequencies for methylated genes stratified by tissue source and methods used were computed.
Results. 51 Studies were identified analyzing 68 different genes for methylation in 4376 specimens across all stages of cervical carcinogenesis. 15 genes, DAPK1, RASSF1, CDH1, CDKN2A, MGMT, RARB, APC, FHIT, MLH1, TIMP3, GSTP1, CADM1, CDH13, HIC1, and TERT have been analyzed in 5 or more studies. The published data on these genes is highly heterogeneous; 7 genes (CDH1, FHIT, TERT, CDH13, MGMT, TIMP3, and HIC1) had a reported range of methylation frequencies in cervical cancers of greater than 60% between studies. Stratification by analysis method did not resolve the heterogeneity. Three markers, DAPK1, CADM1, and RARB, showed elevated methylation in cervical cancers consistently across studies.
Conclusions. There is currently no methylation marker that can be readily translated for use in cervical cancer screening or triage settings. Large, well-conducted methylation profiling Studies of cervical carcinogenesis could yield new candidates that are more specific for HPV-related carcinogenesis. New candidate markers need to be thoroughly validated in highly standardized assays. Published by Elsevier Inc.
C1 [Wentzensen, Nicolas; Sherman, Mark E.; Schiffman, Mark; Wang, Sophia S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20854 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5012, Rockville, MD 20854 USA.
EM wentzenn@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010124-12]
NR 62
TC 135
Z9 146
U1 0
U2 9
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 FEB
PY 2009
VL 112
IS 2
BP 293
EP 299
DI 10.1016/j.ygyno.2008.10.012
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 404JS
UT WOS:000263148400002
PM 19054549
ER
PT J
AU Bosquet, JG
Calcei, J
Wei, JS
Garcia-Closas, M
Sherman, ME
Hewitt, S
Vockley, J
Gerhard, D
Teng, D
Khan, J
Chanock, SJ
AF Bosquet, J. Gonzalez
Calcei, J.
Wei, J. S.
Garcia-Closas, M.
Sherman, M. E.
Hewitt, S.
Vockley, J.
Gerhard, D.
Teng, D.
Khan, J.
Chanock, S. J.
TI Scanning of somatic mutations by high-resolution DNA melting analysis in
gynecologic tumors
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Bosquet, J. Gonzalez; Calcei, J.; Chanock, S. J.] Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Wei, J. S.; Khan, J.] Natl Canc Inst, Adv Technol Ctr, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD USA.
[Sherman, M. E.] Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Hewitt, S.] Natl Canc Inst, Tissue Array Res Program, Bethesda, MD USA.
[Vockley, J.; Gerhard, D.] Natl Canc Inst, Off Canc Genom, Bethesda, MD USA.
[Teng, D.] Idaho Technol, Salt Lake City, UT USA.
NR 0
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 FEB
PY 2009
VL 112
IS 2
MA 231
BP S117
EP S118
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200230
ER
PT J
AU Davidson, B
Elstrand, MB
Kleinberg, L
Kohn, EC
Trope, C
AF Davidson, B.
Elstrand, M. Bunkholt
Kleinberg, L.
Kohn, E. C.
Trope, C.
TI Expression and clinical role of antiapoptotic proteins of the bag, heat
shock, and Bcl-2 families in effusions, primary tumors and solid
metastases in ovarian carcinoma
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Davidson, B.; Kleinberg, L.] Univ Hosp, Rikshosp, Dept Pathol, Norwegian Radium Hosp, Oslo, Norway.
[Elstrand, M. Bunkholt; Trope, C.] Univ Hosp, Rikshosp, Dept Obstet & Gynecol, Norwegian Radium Hosp, Oslo, Norway.
[Kohn, E. C.] NCI, Mol Signaling Sect, Med Oncol Branch, Canc Res Ctr,NIH, Bethesda, MD USA.
NR 0
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 FEB
PY 2009
VL 112
IS 2
MA 252
BP S129
EP S129
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200251
ER
PT J
AU Kinney, W
Fetterman, B
Akhtar, I
Husain, M
Gold, MA
Guido, R
Castle, PE
AF Kinney, W.
Fetterman, B.
Akhtar, I.
Husain, M.
Gold, M. A.
Guido, R.
Castle, P. E.
TI Age-appropriate use of human papillomavirus vaccines in the United
States
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kinney, W.] Kaiser Permanente No Calif, Div Gynecol Oncol, Sacramento, CA USA.
[Fetterman, B.] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA.
[Akhtar, I.] Univ Mississippi, Dept Pathol, Jackson, MS 39216 USA.
[Husain, M.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
[Gold, M. A.] Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA.
[Guido, R.] Magee Womens Hosp, Dept Obstet & Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Castle, P. E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2009
VL 112
IS 2
MA 64
BP S34
EP S35
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200065
ER
PT J
AU Kuo, DY
Blank, SV
Kim, M
Caputo, TA
Pothuri, B
Hershman, D
Goldman, NA
Ivy, P
Runowicz, CD
Muggia, F
Goldberg, GL
Einstein, MH
AF Kuo, D. Y.
Blank, S. V.
Kim, M.
Caputo, T. A.
Pothuri, B.
Hershman, D.
Goldman, N. A.
Ivy, P.
Runowicz, C. D.
Muggia, F.
Goldberg, G. L.
Einstein, M. H.
TI Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer:
A New York Cancer Consortium study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kuo, D. Y.; Goldberg, G. L.; Einstein, M. H.] Albert Einstein Coll Med, Div Gynecol Oncol, Dept Obstet & Gynecol & Womens Hlth, Montefiore Med Ctr, Bronx, NY 10467 USA.
[Kuo, D. Y.; Kim, M.; Goldberg, G. L.; Einstein, M. H.] Ctr Canc, Bronx, NY USA.
[Blank, S. V.; Pothuri, B.] NYU, Dept Obstet & Gynecol, Div Gynecol Oncol, Sch Med, New York, NY 10016 USA.
[Kim, M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Caputo, T. A.] Cornell Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, New York Presbyterian Weill Med Coll, New York, NY 10021 USA.
[Hershman, D.] Columbia Univ, Dept Med, New York Presbyterian Hosp, New York, NY USA.
[Goldman, N. A.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, New York, NY 10003 USA.
[Ivy, P.] NCI, CTEP, Invest Drug Branch, Bethesda, MD 20892 USA.
[Runowicz, C. D.] Univ Connecticut, Ctr Hlth, Dept Obstet & Gynecol, Carole & Ray Neag Comprehens Canc Ctr, Farmington, CT USA.
[Muggia, F.] NYU, Sch Med, Dept Med, New York, NY USA.
NR 0
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 FEB
PY 2009
VL 112
IS 2
MA 27
BP S15
EP S15
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200028
ER
PT J
AU Lin, YG
Merritt, WM
Spannuth, WA
Nick, AM
Stone, RL
Tsinberg, P
Coleman, RL
Birrer, MJ
Bischoff, F
Sood, AK
AF Lin, Y. G.
Merritt, W. M.
Spannuth, W. A.
Nick, A. M.
Stone, R. L.
Tsinberg, P.
Coleman, R. L.
Birrer, M. J.
Bischoff, F.
Sood, A. K.
TI Rare circulating tumor cells can be reliably and efficiently detected
using a novel microfluidies and micro-electromechanical systems
(MEMS)-based rare cell recovery platform: Preclinical and clinical data
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Lin, Y. G.; Merritt, W. M.; Spannuth, W. A.; Nick, A. M.; Stone, R. L.; Coleman, R. L.; Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Div Gynecol Oncol, Dept Obstet & Gynaecol, Houston, TX 77030 USA.
[Tsinberg, P.; Bischoff, F.] Biocept Inc, San Diego, CA USA.
[Birrer, M. J.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
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 FEB
PY 2009
VL 112
IS 2
MA 230
BP S117
EP S117
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200229
ER
PT J
AU Matthews, KS
Noker, P
Tian, B
Grimes, S
Fulton, R
Schweikart, K
Harris, R
Aurigemma, R
Wang, M
Curiel, DT
Alvarez, RD
AF Matthews, K. S.
Noker, P.
Tian, B.
Grimes, S.
Fulton, R.
Schweikart, K.
Harris, R.
Aurigemma, R.
Wang, M.
Curiel, D. T.
Alvarez, R. D.
TI Identifying the safety profile of Ad5.SSTR/TK.RGD, a novel
infectivity-enhanced bicistronic adenovirus, in anticipation of a phase
I clinical trial in patients with recurrent ovarian cancer and other
selected gynecologic cancers
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Matthews, K. S.] Univ Alabama, Dept Gynecol Oncol, Birmingham, AL USA.
[Noker, P.; Tian, B.; Grimes, S.; Fulton, R.] So Res Inst, Birmingham, AL 35255 USA.
[Schweikart, K.] NCI, Toxicol Pharmacol Branch, Bethesda, MD 20892 USA.
[Harris, R.] SAIC Frederick, Biopharmaceut Dev Program, Frederick, MD USA.
[Aurigemma, R.] NCI, Biol Resources Branch, Bethesda, MD 20892 USA.
[Wang, M.; Curiel, D. T.] Univ Alabama, Dept Human Gene Therapy, Birmingham, AL USA.
NR 0
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 FEB
PY 2009
VL 112
IS 2
MA 219
BP S111
EP S112
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200218
ER
PT J
AU Sood, AK
Mangala, LS
Han, H
Lu, C
Ali-Fehmi, R
Stone, R
Munkarah, A
Spannuth, W
Nick, AM
Lee, J
Shahzad, M
Guven, E
Coleman, RL
Denkbas, E
Birrer, MJ
Lopez-Berestein, G
AF Sood, A. K.
Mangala, L. S.
Han, H.
Lu, C.
Ali-Fehmi, R.
Stone, R.
Munkarah, A.
Spannuth, W.
Nick, A. M.
Lee, J.
Shahzad, M.
Guven, E.
Coleman, R. L.
Denkbas, E.
Birrer, M. J.
Lopez-Berestein, G.
TI In vivo angiogenic gene silencing using chitosan nanoparticles in
ovarian carcinoma
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Sood, A. K.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Sood, A. K.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Ali-Fehmi, R.] Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48202 USA.
[Munkarah, A.] Wayne State Univ, Sch Med, Dept Gynecol Oncol, Detroit, MI USA.
[Guven, E.] Hacettepe Univ, Dept Nanotechnol & Nanomed, Ankara, Turkey.
[Birrer, M. J.] NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA.
[Lopez-Berestein, G.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
NR 0
TC 1
Z9 1
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 FEB
PY 2009
VL 112
IS 2
MA 268
BP S136
EP S137
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200267
ER
PT J
AU Stone, RL
Nick, AM
Spannuth, WA
Bonome, T
Lutgendorf, S
DeGeest, K
Merritt, W
Lin, YG
Gershenson, DM
Coleman, RL
Birrer, MJ
Sood, AK
AF Stone, R. L.
Nick, A. M.
Spannuth, W. A.
Bonome, T.
Lutgendorf, S.
DeGeest, K.
Merritt, W.
Lin, Y. G.
Gershenson, D. M.
Coleman, R. L.
Birrer, M. J.
Sood, A. K.
TI Focal adhesion kinase is a new focus for antiangiogenesis therapy in
ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Stone, R. L.; Nick, A. M.; Spannuth, W. A.; Merritt, W.; Lin, Y. G.; Gershenson, D. M.; Coleman, R. L.; Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Bonome, T.; Birrer, M. J.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Lutgendorf, S.; DeGeest, K.] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA.
NR 0
TC 0
Z9 0
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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2009
VL 112
IS 2
MA 55
BP S30
EP S31
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200056
ER
PT J
AU Tanner, E
Olshen, AB
Bonome, T
Shih, KK
Dao, F
Bogomolniy, F
Chi, DS
Birrer, MJ
Boyd, J
Levine, DA
AF Tanner, E.
Olshen, A. B.
Bonome, T.
Shih, K. K.
Dao, F.
Bogomolniy, F.
Chi, D. S.
Birrer, M. J.
Boyd, J.
Levine, D. A.
TI Gene expression profiling of advanced ovarian cancers to predict the
need for maximal surgical effort
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Tanner, E.; Olshen, A. B.; Shih, K. K.; Dao, F.; Bogomolniy, F.; Chi, D. S.; Levine, D. A.] Mem Sloan Kettering Canc Ctr, Dept Gynecol Surg, New York, NY 10021 USA.
[Bonome, T.; Birrer, M. J.] NCI, Rockville, MD USA.
[Boyd, J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
NR 0
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 FEB
PY 2009
VL 112
IS 2
MA 257
BP S131
EP S132
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 419OY
UT WOS:000264230200256
ER
PT J
AU Ron, E
AF Ron, Elaine
TI OVERESTIMATION OF THYROID CANCER INCIDENCE AFTER CHERNOBYL Reply
SO HEALTH PHYSICS
LA English
DT Letter
ID ACCIDENT; DISEASES; COHORT; RISK
C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Ron, E (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM eron@mail.nih.gov
NR 4
TC 2
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2009
VL 96
IS 2
BP 186
EP 187
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 396LH
UT WOS:000262592700010
ER
PT J
AU Nahavandi, M
Nichols, JP
Hassan, M
Gandjbakhche, A
Kato, GJ
AF Nahavandi, M.
Nichols, J. P.
Hassan, M.
Gandjbakhche, A.
Kato, G. J.
TI Near-infrared spectra absorbance of blood from sickle cell patients and
normal individuals
SO HEMATOLOGY
LA English
DT Article
DE Near-infrared spectroscopy; sickle cell disease; hemoglobin; cerebral
oxygen saturation
ID CEREBRAL OXIMETRY; BRAIN OXYGENATION; DISEASE; TRANSPLANTATION
AB Limited data are available regarding the physicochemical dynamics of tissue hypoxia in sickle cell disease. Studies using near-infrared spectroscopy (NIRS) have reported that patients with sickle cell disease (SCD) have lower cerebral oxygen saturation values (rSO(2)) than normal individuals. The reason SCD patients have subnormal rSO(2) values is not known. It may be related to the degree of anaemia, sickle haemoglobin, disease complications and the possibility of SCD different NIRS absorbance spectra than normal. This study compared NIRS absorbance spectra of blood with adult haemoglobin AA, sickle haemoglobin SS, and AS. Venous blood was collected from SCD (SS and AS) and non-SCD patients (AA). Whole blood, cell free haemoglobin samples were scanned through the wavelength range of 600-1000 nm. The results showed no different NIRS spectra absorbance between the haemoglobin's AA, SS. It thus appears that lower brain oxygen saturation in sickle cell anaemia patients is related to impaired oxygen carrying capacity or delivery by sickle haemoglobin.
C1 [Nahavandi, M.] NHLBI, Pulm & Vasc Med Branch, NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Hassan, M.; Gandjbakhche, A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Nahavandi, M (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA.
EM nahavandim@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Heart, Lung and Blood Institute; National Institute of Child
Health and Human Development; Clinical Center at the National Institute
of Health, Bethesda, MD, USA
FX This research was supported by intramural funding from the National
Heart, Lung and Blood Institute, National Institute of Child Health and
Human Development, and the Clinical Center at the National Institute of
Health, Bethesda, MD, USA.
NR 12
TC 10
Z9 10
U1 1
U2 5
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1024-5332
J9 HEMATOLOGY
JI Hematology
PD FEB
PY 2009
VL 14
IS 1
BP 46
EP 48
DI 10.1179/102453309X385133
PG 3
WC Hematology
SC Hematology
GA 473AE
UT WOS:000268174500007
PM 19154664
ER
PT J
AU Gottwein, JM
Scheel, TKH
Jensen, TB
Lademann, JB
Prentoe, JC
Knudsen, ML
Hoegh, AM
Bukh, J
AF Gottwein, Judith M.
Scheel, Troels K. H.
Jensen, Tanja B.
Lademann, Jacob B.
Prentoe, Jannick C.
Knudsen, Maria L.
Hoegh, Anne M.
Bukh, Jens
TI Development and Characterization of Hepatitis C Virus Genotype 1-7 Cell
Culture Systems: Role of CD81 and Scavenger Receptor Class B Type I and
Effect of Antiviral Drugs
SO HEPATOLOGY
LA English
DT Article
ID CORE PROTEIN; INFECTIOUS VIRUS; MAJOR GENOTYPES; STEATOSIS;
NEUTRALIZATION; CHOLESTEROL; AMANTADINE; MUTATIONS; ASSAY; 5A
AB Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon-a and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (El, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH1 (6a/2a, in E1 and E2) and J4/JFH1 (1b/2a, in NS2 and NS3); viability of J8/JFH1 (2b/2a) and QC69/JFH1 (7a/2a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1-7 recombinants with infectivity titers of 10(3.7) to 10(5.2) 50% tissue culture infectious dose/mL and HCV RNA titers of 10(7.0) to 10(7.9) IU/mL. Huh7.5 cultures infected with genotype 1-6 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-alpha 2b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies against the putative coreceptors CD81 and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype 1-7 viruses. Conclusion: We completed and characterized a panel of JTH1-based cell culture systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies. (HEPATOLOGY 2009;49:364-377.)
C1 [Gottwein, Judith M.; Scheel, Troels K. H.; Jensen, Tanja B.; Lademann, Jacob B.; Prentoe, Jannick C.; Knudsen, Maria L.; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program, Dept Infect Dis, DK-2650 Hvidovre, Denmark.
[Gottwein, Judith M.; Scheel, Troels K. H.; Jensen, Tanja B.; Lademann, Jacob B.; Prentoe, Jannick C.; Knudsen, Maria L.; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Gottwein, Judith M.; Scheel, Troels K. H.; Jensen, Tanja B.; Lademann, Jacob B.; Prentoe, Jannick C.; Knudsen, Maria L.; Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, DK-1168 Copenhagen, Denmark.
[Hoegh, Anne M.] Copenhagen Univ Hosp, Dept Clin Microbiol, Hvidovre, Denmark.
[Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bukh, J (reprint author), Copenhagen Univ Hosp, Copenhagen Hepatitis C Program, Dept Infect Dis, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@niaid.nih.gov
OI Prentoe, Jannick/0000-0003-2203-9478; Scheel, Troels/0000-0003-1545-4067
FU Copenhagen University Hospital, Hvidovre; Novo Nordisk Foundation;
Lundbeck Foundation; Danish Medical Research Council; Danish Cancer
Society
FX This study was supported by Copenhagen University Hospital, Hvidovre
(support to J. M. G., T K. H. S., T B.J., J B. L., and J. B.); Novo
Nordisk Foundation (support to J G. and J. B.); Lundbeck Foundation
(support to J.B.); The Danish Medical Research Council (support to J.
B.); and The Danish Cancer Society (support to J B.).
NR 25
TC 215
Z9 223
U1 0
U2 13
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2009
VL 49
IS 2
BP 364
EP 377
DI 10.1002/hep.22673
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 401EW
UT WOS:000262923300008
PM 19148942
ER
PT J
AU Zhu, F
Park, EM
Liu, BG
Xia, XJ
Fischer, SM
Hu, YL
AF Zhu, Feng
Park, Eunmi
Liu, Bigang
Xia, Xiaojun
Fischer, Susan M.
Hu, Yinling
TI Critical role of I kappa B kinase alpha in embryonic skin development
and skin carcinogenesis
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE I kappa B kinase alpha (IKK alpha); Embryonic skin development; Skin
carcinogenesis; Nuclear factor-kappaB (NF-kappa B)
ID SQUAMOUS-CELL CARCINOMAS; H3 LYSINE-9 METHYLATION; HELIX-LOOP-HELIX;
IKK-ALPHA; HISTONE H3; DNA METHYLATION; MICE LACKING; EPIGENETIC
INACTIVATION; TUMOR PROGRESSION; ACTIVATION
AB I kappa B kinase alpha (IKK alpha), IKK beta, and IKK gamma/NEMO form the IKK complex, which is essential for NF-kappa B activation. However, genetic studies have shown that the role of IKK alpha is distinct from that of IKK alpha or IKK gamma in the development of the mouse embryonic skin. Loss of IKK alpha has been shown to cause epidermal hyperplasia, prevent keratinocyte terminal differentiation, and impair the formation of the skin, resulting in the deaths of IKK alpha-deficient (Ikk alpha(-/-)) mice soon after birth. Recent experimental data from several laboratories have revealed that IKK alpha functions as a tumor suppressor in human squamous cell carcinomas (SCCs) of skin, lungs, and head and neck. Chemical carcinogenesis studies using mice have shown that reduction in IKK alpha expression increases the number and size of Ras-initiated skin tumors and promotes their progression, indicating that reduced IKK alpha expression provides a selective growth advantage that cooperates with Ras activity to promote skin carcinogenesis. In this review, we will summarize these findings from our and other studies on the role that IKK alpha plays in development of the mouse embryonic skin and skin carcinogenesis.
C1 [Hu, Yinling] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
[Zhu, Feng; Park, Eunmi; Liu, Bigang; Xia, Xiaojun; Fischer, Susan M.; Hu, Yinling] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA.
RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
EM huy2@mail.nih.gov
FU National Cancer Institute grants [CA102510, CA117314, CA105345,
CA16672]; National Institute of Environmental Health Sciences Center
[ES07784]
FX The studies reviewed in this article were supported by National Cancer
Institute grants CA102510 and CA117314 (to Y.H.), CA105345 (to S.M.F.),
and CA16672 (M. D. Anderson Cancer Center Core Grant), and by the
National Institute of Environmental Health Sciences Center Grant
ES07784.
NR 51
TC 16
Z9 16
U1 0
U2 1
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD FEB
PY 2009
VL 24
IS 2
BP 265
EP 271
PG 7
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 383TR
UT WOS:000261696900013
PM 19085841
ER
PT J
AU Valcour, V
Yeh, TM
Bartt, R
Clifford, D
Gerschenson, M
Evans, SR
Cohen, BA
Ebenezer, GJ
Hauer, P
Millar, L
Gould, M
Tran, P
Shikuma, C
Souza, S
McArthur, JC
AF Valcour, V.
Yeh, T-M
Bartt, R.
Clifford, D.
Gerschenson, M.
Evans, S. R.
Cohen, B. A.
Ebenezer, G. J.
Hauer, P.
Millar, L.
Gould, M.
Tran, P.
Shikuma, C.
Souza, S.
McArthur, J. C.
CA AIDS Clinical Trials Grp ACTG 5157
Protocol Team
TI Acetyl-L-carnitine and nucleoside reverse transcriptase
inhibitor-associated neuropathy in HIV infection
SO HIV MEDICINE
LA English
DT Article
DE fat; HIV; mitochondria; neuropathy
ID ANTIRETROVIRAL TOXIC NEUROPATHY; BLOOD MONONUCLEAR-CELLS; PERIPHERAL
NEUROPATHY; RISK-FACTORS; MITOCHONDRIAL TOXICITY; NATURAL-HISTORY;
MANAGEMENT; ANALOGS; AIDS; DNA
AB Objectives Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-L-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA ( mtDNA) copies/cell among subjects treated with 3000 mg ALC daily.
Methods Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed.
Results Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of - 1.70 (- 3.50, infinity) (P=0.98) and 2.15 (- 0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P < 0.01), paresthesias ( P=0.01), and symptoms of numbness ( P < 0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score.
Conclusions ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.
C1 [Valcour, V.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Valcour, V.; Gerschenson, M.; Shikuma, C.; Souza, S.] Univ Hawaii, John A Burns Sch Med, Hawaii AIDS Clin Res Program, Honolulu, HI 96822 USA.
[Yeh, T-M; Evans, S. R.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Bartt, R.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Bartt, R.] Cook Cty Hosp, Chicago, IL 60612 USA.
[Clifford, D.; Gould, M.] Washington Univ, Sch Med, St Louis, MO USA.
[Cohen, B. A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ebenezer, G. J.; Hauer, P.; McArthur, J. C.] Johns Hopkins Univ, Baltimore, MD USA.
[Millar, L.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Tran, P.] NIAID, Pharmaceut Affairs Branch, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Valcour, V (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 350 Parnassus Ave,Suite 706, San Francisco, CA 94143 USA.
EM Vvalcour@hawaii.edu
FU NCRR NIH HHS [RR025005]; NIAID NIH HHS [3U01AI046376-05S4, AI 069471,
AI069434, AI069465, AI069471, AI069495, AI069556-02, AI25915-(15-20),
AI34853, AI38855, AI38858, AI46370, AI68634, AI68636, U01 AI034853, U01
AI038855, U01 AI038858, U01 AI068634, U01 AI068636, U01 AI069471, U01
AI069495, U01 AI069495-03, UM1 AI068634, UM1 AI068636, UM1 AI069471, UM1
AI069495]; NIMH NIH HHS [MH075673]; NIMHD NIH HHS [MD000173, P20
MD000173]; NINDS NIH HHS [NS0322228, NS032228-10, NS32228, NS44807, R01
NS032228, U01 NS032228, U01 NS032228-12]; PHS HHS [5 U01 A1069415-02]
NR 29
TC 15
Z9 15
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-2662
J9 HIV MED
JI HIV Med.
PD FEB
PY 2009
VL 10
IS 2
BP 103
EP 110
DI 10.1111/j.1468-1293.2008.00658.x
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 397DB
UT WOS:000262641200006
PM 19200173
ER
PT J
AU Keil, A
Sabatinelli, D
Ding, MZ
Lang, PJ
Ihssen, N
Heim, S
AF Keil, Andreas
Sabatinelli, Dean
Ding, Mingzhou
Lang, Peter J.
Ihssen, Niklas
Heim, Sabine
TI Re-entrant Projections Modulate Visual Cortex in Affective Perception:
Evidence From Granger Causality Analysis
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE affective arousal; electroencephalography; emotion; Granger causality;
steady-state potentials
ID MOTIVATED ATTENTION; BRAIN POTENTIALS; CORTICAL AREAS; FEAR; ACTIVATION;
MECHANISMS; EEG; CONNECTIONS; RESPONSES; NETWORKS
AB Re-entrant modulation of visual cortex has been suggested as a critical process for enhancing perception of emotionally arousing visual stimuli. This study explores how the time information inherent in large-scale electrocortical measures can be used to examine the functional relationships among the structures involved in emotional perception. Granger causality analysis was conducted on steady-state visual evoked potentials elicited by emotionally arousing pictures flickering at a rate of 10 Hz. This procedure allows one to examine the direction of neural connections. Participants viewed pictures that varied in emotional content, depicting people in neutral contexts, erotica, or interpersonal attack scenes. Results demonstrated increased Coupling between visual and cortical areas when viewing emotionally arousing content. Specifically, intraparietal to inferotemporal and precuneus to calcarine connections were stronger for emotionally arousing picture content. Thus, we provide evidence for re-entrant signal flow during emotional perception, which originates from higher tiers and enters lower tiers of visual cortex. Hum Brain Mapp 30:532-540, 2009. (C) 2007 Wiley-Liss, Inc.
C1 [Keil, Andreas; Sabatinelli, Dean; Lang, Peter J.] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA.
[Ding, Mingzhou] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Ihssen, Niklas; Heim, Sabine] Univ Konstanz, Dept Psychol, Constance, Germany.
RP Keil, A (reprint author), Univ Florida, Dept Psychol, POB 112766, Gainesville, FL 32611 USA.
EM akeil@ufl.edu
RI Ihssen, Niklas/B-6324-2012; Keil, Andreas/F-9427-2011;
OI Ihssen, Niklas/0000-0001-8386-1524; Keil, Andreas/0000-0002-4064-1924;
sabatinelli, dean/0000-0001-7409-8504
FU Deutsche Forschungsgemeinschaft; National Institute of Mental Health
(NIMH); Center for the Study of Emotion and Attention (CSEA); University
of Florida [P50-MH52384]
FX Deutsche Forschungsgemeinschaft; Contract grant sponsor: National
Institute of Mental Health (NIMH) (Behavioral Science grant to the
Center for the Study of Emotion and Attention (CSEA), University of
Florida); Contract grant number: P50-MH52384.
NR 51
TC 69
Z9 69
U1 2
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD FEB
PY 2009
VL 30
IS 2
BP 532
EP 540
DI 10.1002/hbm.20521
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 405NZ
UT WOS:000263232800016
PM 18095279
ER
PT J
AU Portier, C
AF Portier, C.
TI Toxicological decision-making on hazards and risks - status quo and way
forward
SO HUMAN & EXPERIMENTAL TOXICOLOGY
LA English
DT Article; Proceedings Paper
CT 1st International Forum Towards Evidence-Based Toxicology
CY OCT 15-15, 2007
CL Como, ITALY
C1 Natl Inst Environm Hlth Sci, Off Risk Assessment Res, Res Triangle Pk, NC 27709 USA.
RP Portier, C (reprint author), Natl Inst Environm Hlth Sci, Off Risk Assessment Res, Res Triangle Pk, NC 27709 USA.
RI Portier, Christopher/A-3160-2010
OI Portier, Christopher/0000-0002-0954-0279
NR 3
TC 1
Z9 1
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0960-3271
J9 HUM EXP TOXICOL
JI Hum. Exp. Toxicol.
PD FEB-MAR
PY 2009
VL 28
IS 2-3
BP 123
EP 125
DI 10.1177/0960327109105768
PG 3
WC Toxicology
SC Toxicology
GA 489IM
UT WOS:000269413700013
PM 19713376
ER
PT J
AU Cullinane, AR
Straatman-Iwanowska, A
Seo, JK
Ko, JS
Song, KS
Gizewska, M
Gruszfeld, D
Gliwicz, D
Tuysuz, B
Erdemir, G
Sougrat, R
Wakabayashi, Y
Hinds, R
Barnicoat, A
Mandel, H
Chitayat, D
Fischler, B
Garcia-Cazorla, A
Knisely, AS
Kelly, DA
Maher, ER
Gissen, P
AF Cullinane, Andrew R.
Straatman-Iwanowska, Anna
Seo, Jeong K.
Ko, Jae S.
Song, Kyung S.
Gizewska, Maria
Gruszfeld, Dariusz
Gliwicz, Dorota
Tuysuz, Beyhan
Erdemir, Gulin
Sougrat, Rachid
Wakabayashi, Yoshiyuki
Hinds, Rupert
Barnicoat, Angela
Mandel, Hanna
Chitayat, David
Fischler, Bjorn
Garcia-Cazorla, Angels
Knisely, A. S.
Kelly, Deirdre A.
Maher, Eamonn R.
Gissen, Paul
TI Molecular Investigations to Improve Diagnostic Accuracy in Patients With
ARC Syndrome
SO HUMAN MUTATION
LA English
DT Article
DE arthrogryposis; renal tubular dysfunction; neonatal cholestasis; ARC;
vesicular trafficking defect
ID RENAL DYSFUNCTION; ARTHROGRYPOSIS; CHOLESTASIS; VPS33B; MUTATION
AB Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a multi-system autosomal recessive disorder caused by germline mutations in VPS33B. The detection of germline VPS33B mutations removes the need for diagnostic organ biopsies (these carry a >50% risk of life-threatening haemorrhage due to platelet dysfunction); however, VPS33B mutations are not detectable in similar to 25% of patients. In order further to define the molecular basis of ARC we performed mutation analysis and mRNA and protein studies in patients with a clinical diagnosis of ARC. Here we report novel mutations in VPS33B in patients from Eastern Europe and South East Asia. One of the mutations was present in 7 unrelated Korean patients. Reduced expression of VPS33B and cellular phenotype was detected in fibroblasts from patients clinically diagnosed with ARC with and without known VPS33B mutations. One mutation-negative patient was found to have normal mRNA and protein levels. This patient's clinical condition improved and he is alive at the age of 2.5 years. Thus we show that all patients with a classical clinical course of ARC had decreased expression of VPS33B whereas normal VPS33B expression was associated with good prognosis despite initial diagnosis of ARC. (C) 2008 Wiley-Liss, Inc.
C1 [Gissen, Paul] Univ Birmingham, Sch Med, Inst Biomed Res W, Dept Med & Mol Genet, Birmingham B15 2TT, W Midlands, England.
[Seo, Jeong K.; Ko, Jae S.] Seoul Natl Univ, Coll Med, Dept Pediat, Seoul, South Korea.
[Song, Kyung S.] YongDong Severance Hosp, Dept Lab Med, Seoul, South Korea.
[Gizewska, Maria] Pomeranian Med Univ, Dept Paediat 2, Szczecin, Poland.
[Gruszfeld, Dariusz] Childrens Mem Hlth Inst Warsaw, Dept Neonatol, Warsaw, Poland.
[Gliwicz, Dorota] Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol & Immunol, Warsaw, Poland.
[Tuysuz, Beyhan] Istanbul Univ, Dept Pediat Genet, Cerrahpasa Med Fac, Istanbul, Turkey.
[Erdemir, Gulin] Uludag Univ, Fac Med, Dept Pediat Gastroenterol Hepatol & Nutr, Gorukle, Bursa, Turkey.
[Sougrat, Rachid; Wakabayashi, Yoshiyuki] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD USA.
[Hinds, Rupert; Knisely, A. S.] Kings Coll Hosp, Inst Liver Studies, London, England.
[Barnicoat, Angela] Great Ormond St Hosp Sick Children, Dept Genet, London WC1N 3JH, England.
[Mandel, Hanna] Technion Israel Inst Technol, Rambam Med Ctr, Fac Med, Meyer Childrens Hosp,Metab Unit, Haifa, Israel.
[Chitayat, David] Univ Toronto, Hosp Sick Children, Dept Paediat, Div Clin & Metab Genet, Toronto, ON M5S 1A1, Canada.
[Fischler, Bjorn] Karolinska Univ Hosp, Childrens Hosp, Huddinge, Sweden.
[Garcia-Cazorla, Angels] Inst Salud Carlos III, Ctr Biomed Res & Rare Dis CIBER ER, Madrid, Spain.
[Garcia-Cazorla, Angels] Hosp St Joan de Deu, Barcelona, Spain.
[Kelly, Deirdre A.] Birmingham Childrens Hosp, Liver Unit, Birmingham, W Midlands, England.
[Maher, Eamonn R.] Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Gissen, Paul] Birmingham Childrens Hosp, Metab Unit, Birmingham, W Midlands, England.
RP Gissen, P (reprint author), Univ Birmingham, Sch Med, Inst Biomed Res W, Dept Med & Mol Genet, Wolfson Dr, Birmingham B15 2TT, W Midlands, England.
EM p.gissen@bham.ac.uk
RI Gissen, Paul/A-4352-2010; Seo, Jeong Kee/J-5512-2012; Gizewska,
Maria/B-3020-2015;
OI Gissen, Paul/0000-0002-9712-6122; Sougrat, Rachid/0000-0001-6476-1886
FU Children's Liver Disease Foundation (CLDF); ARC syndrome association;
Children Living with Inherited Metabolic Diseases (CLIMB); Intramural
Program of Eunice Kennedy Shriver National Institute of Child Health and
Human Development; National Institutes of Health; Birmingham Children's
Hospital Research Foundation (BCHRF)
FX PG is a GSK Clinician Scientist. Authors thank all the families and
clinicians who contributed to this research. Authors also wish to thank
Children's Liver Disease Foundation (CLDF), ARC syndrome association,
Children Living with Inherited Metabolic Diseases (CLIMB), the
Intramural Program of Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health and
Birmingham Children's Hospital Research Foundation (BCHRF) for their
generous support.
NR 10
TC 11
Z9 13
U1 0
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 FEB
PY 2009
VL 30
IS 2
BP E330
EP E337
DI 10.1002/humu.20900
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 626PQ
UT WOS:000279979200003
PM 18853461
ER
PT J
AU Zhu, JL
Basso, O
Obel, C
Bech, BH
Nohr, EA
Shrestha, A
Olsen, J
AF Zhu, Jin Liang
Basso, Olga
Obel, Carsten
Bech, Bodil Hammer
Nohr, Ellen Aagaard
Shrestha, Anshu
Olsen, Jorn
TI Parental infertility and sexual maturation in children
SO HUMAN REPRODUCTION
LA English
DT Article
ID ASSISTED REPRODUCTIVE TECHNOLOGY; SECULAR TREND; SEMEN QUALITY; DENMARK;
HEALTH; AGE; HYPOSPADIAS; MENARCHE; PUBERTY; BOYS
AB The reproductive health of children born of infertile couples may be affected by infertility treatment or factors associated with infertility. We examined sexual maturation in children of parents with infertility.
We used data from a follow-up of 3382 girls and 2810 boys born between 1984 and 1987 in the Aalborg-Odense Birth Cohort. We had mothers' report of time to pregnancy (TTP) and infertility treatment (at the time, mostly hormonal) from the pregnancy questionnaire administered in 1984-1987, and the children's report of their own sexual maturation from the follow-up questionnaire administered in 2005, when they were between 18 and 21 years old. Many reported age only in year when they had the events related to sexual maturation, and for each event, we imputed the month based on the median month at each year of age among those reporting both years and months.
In girls, the mean age at menarche was 13.3 years and, in boys, the mean age at appearance of acne, voice break, regular shaving and first nocturnal emission were 14.5, 14.5, 17.2 and 14.7 years, respectively. We saw no significant differences in age at these events among children born of either fertile (with TTP of 0-12 months and no treatment), untreated infertile (with TTP of more than 12 months and no treatment) or treated infertile couples (with a history of examination or treatment for infertility).
Our data suggest no significant association between parental infertility or hormonal treatment and timing of sexual maturation in the offspring.
C1 [Zhu, Jin Liang; Obel, Carsten; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Olsen, Jorn] Univ Aarhus, Inst Publ Hlth, Dept Epidemiol, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark.
[Basso, Olga] NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Obel, Carsten] Aarhus Univ Hosp, Dept Obstet & Gynaecol, Perinatal Epidemiol Res Unit, DK-8200 Aarhus N, Denmark.
[Shrestha, Anshu; Olsen, Jorn] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
RP Zhu, JL (reprint author), Univ Aarhus, Inst Publ Hlth, Dept Epidemiol, Danish Epidemiol Sci Ctr, Vennelyst Blvd 6, DK-8000 Aarhus C, Denmark.
EM zjl@soci.au.dk
RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015; Bech, Bodil
Hammer/B-9646-2016
OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140;
FU Danish Medical Research Council [271-05-0115]; NIH; National Institute
of Environmental Health Sciences [Z01 ES044003]
FX This work was supported by a grant from the Danish Medical Research
Council (271-05-0115) and, in part, by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (Z01
ES044003).
NR 24
TC 2
Z9 4
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD FEB
PY 2009
VL 24
IS 2
BP 445
EP 450
DI 10.1093/humrep/den366
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 395JD
UT WOS:000262519500025
PM 18840889
ER
PT J
AU Louis, GMB
Dmochowski, J
Lynch, C
Kostyniak, P
McGuinness, BM
Vena, JE
AF Louis, G. M. Buck
Dmochowski, J.
Lynch, C.
Kostyniak, P.
McGuinness, B. M.
Vena, J. E.
TI Polychlorinated biphenyl serum concentrations, lifestyle and
time-to-pregnancy
SO HUMAN REPRODUCTION
LA English
DT Article
ID MENSTRUAL-CYCLE; FERTILE WINDOW; ALCOHOL INTAKE; ANGLER COHORT; WAITING
TIME; FECUNDABILITY; CONSUMPTION; EXPOSURE; INFERTILITY; FECUNDITY
AB Consumption of fish contaminated with polychlorinated biphenyls (PCBs) and prenatal PCB serum concentrations have been associated with a longer time-to-pregnancy (TTP). However, the relationship between preconception serum PCBs concentrations and TTP has not been previously studied.
Eighty-three women (contributing 442 menstrual cycles) planning pregnancies completed daily diaries regarding menstruation, intercourse, home pregnancy test results, and reported use of alcohol and cigarettes. TTP denoted the number of observed menstrual cycles required for pregnancy. Preconception blood specimens underwent toxicologic analysis for 76 PCB congeners via gas chromatography with electron capture; serum lipids were quantified with enzymatic methods. A priori, PCB congeners were summed into a total and three groupings-025EFestrogenic, anti-estrogenic and other-025EFand entered into discrete analogs of Cox models with time-varying covariates to estimate fecundability odds ratios (FOR) and corresponding 95% confidence intervals (CIs).
Estrogenic and anti-estrogenic PCB concentrations (ng/g serum) conferred reduced FORs in fully adjusted models (0.32; 95% CI 0.03, 3.90 and 0.01: 95% CI < 0.00, 1.99, respectively). Reduced FORs (0.96) were observed for alcohol consumption standardized to a 28-day menstrual cycle in the same adjusted model (FOR = 0.96; 95% CI 0.93, 1.00).
These data suggest that environmental exposures including those amenable to change, such as alcohol consumption, may impact female fecundity. The findings are sensitive to model specification and PCB groupings, underscoring the need to further assess the impact of chemical mixtures on sensitive reproductive outcomes, such as TTP, especially in the context of lifestyle factors which are amenable to change, thereby improving reproductive health.
C1 [Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD 20852 USA.
[Dmochowski, J.] Univ N Carolina, Dept Math & Stat, Charlotte, NC 28223 USA.
[Lynch, C.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Kostyniak, P.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Toxicol, Buffalo, NY 14214 USA.
[McGuinness, B. M.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA.
[Vena, J. E.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29201 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Rm 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Great Lakes Protection Fund [RM791-3021]; Agency for Toxic Substances
and Disease Registry [H751 ATH 298338]; Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Supported in part with funding from the Great Lakes Protection Fund
(RM791-3021), the Agency for Toxic Substances and Disease Registry (H751
ATH 298338) and the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 39
TC 37
Z9 37
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD FEB
PY 2009
VL 24
IS 2
BP 451
EP 458
DI 10.1093/humrep/den373
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 395JD
UT WOS:000262519500026
ER
PT J
AU Tang, JS
Rangayyan, R
Yao, JH
Yang, YY
AF Tang, Jinshan
Rangayyan, Raj
Yao, Jianhua
Yang, Yongyi
TI Introduction to the Issue on Digital Image Processing Techniques for
Oncology
SO IEEE JOURNAL OF SELECTED TOPICS IN SIGNAL PROCESSING
LA English
DT Editorial Material
C1 [Tang, Jinshan] Alcorn State Univ, Dept Adv Technol, Lorman, MS 39096 USA.
[Rangayyan, Raj] Univ Calgary, Dept Elect & Comp Engn, Schulich Sch Engn, Calgary, AB T2N 1N4, Canada.
[Yao, Jianhua] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Yang, Yongyi] IIT, Dept Elect & Comp Engn, Chicago, IL 60616 USA.
RP Tang, JS (reprint author), Alcorn State Univ, Dept Adv Technol, Lorman, MS 39096 USA.
EM jtang@alcorn.edu; ranga@enel.ucalgary.ca; JYao@cc.nih.gov;
yy@ece.iit.edu
NR 0
TC 3
Z9 3
U1 0
U2 1
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA
SN 1932-4553
J9 IEEE J-STSP
JI IEEE J. Sel. Top. Signal Process.
PD FEB
PY 2009
VL 3
IS 1
BP 1
EP 3
DI 10.1109/JSTSP.2009.2013533
PG 3
WC Engineering, Electrical & Electronic
SC Engineering
GA 437OC
UT WOS:000265495800001
ER
PT J
AU Yao, JH
Chen, J
Chow, C
AF Yao, Jianhua
Chen, Jeremy
Chow, Catherine
TI Breast Tumor Analysis in Dynamic Contrast Enhanced MRI Using Texture
Features and Wavelet Transform
SO IEEE JOURNAL OF SELECTED TOPICS IN SIGNAL PROCESSING
LA English
DT Article
DE Breast cancer; dynamic contrast enhanced MRI; texture analysis; wavelet
transform
ID PARAMETERS
AB Dynamic contrast enhanced MRI (DCE-MRI) is an emerging imaging protocol in locating, identifying and characterizing breast cancer. However, due to image artifacts in MR, pixel intensity alone cannot accurately characterize the tissue properties. We propose a robust method based on the temporal sequence of textural change and wavelet transform for pixel-by-pixel classification. We first segment the breast region using an active contour model. We then compute textural change on pixel blocks. We apply a three-scale discrete wavelet transform on the texture temporal sequence to further extract frequency features. We employ a progressive feature selection scheme and a committee of support vector machines for the classification. We trained the system on ten cases and tested it on eight independent test cases. Receiver-operating characteristics (ROC) analysis shows that the texture temporal sequence (Az: 0.966 and 0.949 in training and test) is much more effective than the intensity sequence (Az: 0.871 and 0.868 in training and test). The wavelet transform further improves the classification performance (Az: 0.989 and 0.984 in training and test).
C1 [Yao, Jianhua; Chen, Jeremy; Chow, Catherine] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM jyao@cc.nih.gov
FU National Institutes of Health, Clinical Center
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Center. The Guest Editor
coordinating the review of this manuscript and approving it for
publication was Dr. Jinshan Tang.
NR 28
TC 13
Z9 13
U1 0
U2 8
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA
SN 1932-4553
J9 IEEE J-STSP
JI IEEE J. Sel. Top. Signal Process.
PD FEB
PY 2009
VL 3
IS 1
BP 94
EP 100
DI 10.1109/JSTSP.2008.2011110
PG 7
WC Engineering, Electrical & Electronic
SC Engineering
GA 437OC
UT WOS:000265495800011
ER
PT J
AU Shamir, L
Ling, SM
Scott, WW
Bos, A
Orlov, N
Macura, TJ
Eckley, DM
Ferrucci, L
Goldberg, IG
AF Shamir, Lior
Ling, Shari M.
Scott, William W., Jr.
Bos, Angelo
Orlov, Nikita
Macura, Tomasz J.
Eckley, D. Mark
Ferrucci, Luigi
Goldberg, Ilya G.
TI Knee X-Ray Image Analysis Method for Automated Detection of
Osteoarthritis
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Automated detection; image classification; Kellgren-Lawrence (KL)
classification; osteoarthritis (OA); X-ray
ID QUANTITATIVE-ANALYSIS; CARTILAGE; FEATURES; HIP; INFORMATICS;
COMPUTATION; SEVERITY; MOMENTS; BONE
AB We describe a method for automated detection of radiographic osteoarthritis (OA) in knee X-ray images. The detection is based on the Kellgren-Lawrence (KL) classification grades, which correspond to the different stages of OA severity. The classifier was built using manually classified X-rays, representing the first four KL grades (normal, doubtful, minimal, and moderate). Image analysis is performed by first identifying a set of image content descriptors and image transforms that are informative for the detection of OA in the X-rays and assigning weights to these image features using Fisher scores. Then, a simple weighted nearest neighbor rule is used in order to predict the KL grade to which a given test X-ray sample belongs. The dataset used in the experiment contained 350 X-ray images classified manually by their KL grades. Experimental results show that moderate OA (KL grade 3) and minimal OA (KL grade 2) can be differentiated from normal cases with accuracy of 91.5% and 80.4%, respectively. Doubtful OA (KL grade 1) was detected automatically with a much lower accuracy of 57%. The source code developed and used in this study is available for free download at www.openmicroscopy.org.
C1 [Shamir, Lior; Orlov, Nikita; Macura, Tomasz J.; Eckley, D. Mark; Goldberg, Ilya G.] NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Ling, Shari M.; Bos, Angelo; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21225 USA.
[Ling, Shari M.] Johns Hopkins Univ, Sch Med, Div Geriatr Med Gerontol & Rheumatol, Baltimore, MD 21205 USA.
[Ling, Shari M.] Univ Maryland, College Pk, MD 20742 USA.
[Scott, William W., Jr.] Johns Hopkins Sch Med, Ctr Arthritis, Baltimore, MD 21205 USA.
[Macura, Tomasz J.] Univ Cambridge Trinity Coll, Comp Lab, Cambridge CB2 1TQ, England.
RP Shamir, L (reprint author), NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM shamirl@mail.nih.gov
RI Goldberg, Ilya/H-5307-2011; Eckley, Mark/M-3526-2014
OI Goldberg, Ilya/0000-0001-8514-6110; Eckley, Mark/0000-0003-2296-5164
FU Intramural Research Program; National Institute on Aging; National
Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program, National
Institute on Aging, National Institutes of Health (NIH).
NR 37
TC 31
Z9 32
U1 0
U2 1
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD FEB
PY 2009
VL 56
IS 2
BP 407
EP 415
DI 10.1109/TBME.2008.2006025
PG 9
WC Engineering, Biomedical
SC Engineering
GA 435VZ
UT WOS:000265372700025
PM 19342330
ER
PT J
AU Beare, PA
Unsworth, N
Andoh, M
Voth, DE
Omsland, A
Gilk, SD
Williams, KP
Sobral, BW
Kupko, JJ
Porcella, SF
Samuel, JE
Heinzen, RA
AF Beare, Paul A.
Unsworth, Nathan
Andoh, Masako
Voth, Daniel E.
Omsland, Anders
Gilk, Stacey D.
Williams, Kelly P.
Sobral, Bruno W.
Kupko, John J., III
Porcella, Stephen F.
Samuel, James E.
Heinzen, Robert A.
TI Comparative Genomics Reveal Extensive Transposon-Mediated Genomic
Plasticity and Diversity among Potential Effector Proteins within the
Genus Coxiella
SO INFECTION AND IMMUNITY
LA English
DT Review
ID NECROSIS-FACTOR-ALPHA; IV SECRETION SYSTEM; LEGIONELLA-PNEUMOPHILA;
Q-FEVER; PHASE-I; MOLECULAR CHARACTERIZATION; CHLAMYDIA-TRACHOMATIS;
PHYLOGENETIC ANALYSIS; BACTERIAL PATHOGENS; REPEAT PROTEINS
AB Genetically distinct isolates of Coxiella burnetii, the cause of human Q fever, display different phenotypes with respect to in vitro infectivity/cytopathology and pathogenicity for laboratory animals. Moreover, correlations between C. burnetii genomic groups and human disease presentation ( acute versus chronic) have been described, suggesting that isolates have distinct virulence characteristics. To provide a more-complete understanding of C. burnetii's genetic diversity, evolution, and pathogenic potential, we deciphered the whole-genome sequences of the K (Q154) and G (Q212) human chronic endocarditis isolates and the naturally attenuated Dugway (5J108-111) rodent isolate. Cross-genome comparisons that included the previously sequenced Nine Mile (NM) reference isolate (RSA493) revealed both novel gene content and disparate collections of pseudogenes that may contribute to isolate virulence and other phenotypes. While C. burnetii genomes are highly syntenous, recombination between abundant insertion sequence ( IS) elements has resulted in genome plasticity manifested as chromosomal rearrangement of syntenic blocks and DNA insertions/deletions. The numerous IS elements, genomic rearrangements, and pseudogenes of C. burnetii isolates are consistent with genome structures of other bacterial pathogens that have recently emerged from nonpathogens with expanded niches. The observation that the attenuated Dugway isolate has the largest genome with the fewest pseudogenes and IS elements suggests that this isolate's lineage is at an earlier stage of pathoadaptation than the NM, K, and G lineages.
C1 [Beare, Paul A.; Voth, Daniel E.; Omsland, Anders; Gilk, Stacey D.; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect, Hamilton, MT 59840 USA.
[Kupko, John J., III; Porcella, Stephen F.] NIAID, Rocky Mt Labs, Genom Core Facil, Res Technol Branch, Hamilton, MT 59840 USA.
[Unsworth, Nathan; Andoh, Masako; Samuel, James E.] Texas A& M Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA.
[Williams, Kelly P.; Sobral, Bruno W.] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect, 903 S 4th St, Hamilton, MT 59840 USA.
EM rheinzen@niaid.nih.gov
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases [AI057156]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases ( R. A. H.), and by Public Heath Service grant
AI057156 from the National Institute of Allergy and Infectious Diseases
( J. E. S.).
NR 113
TC 100
Z9 832
U1 3
U2 21
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 FEB
PY 2009
VL 77
IS 2
BP 642
EP 656
DI 10.1128/IAI.01141-08
PG 15
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 399CF
UT WOS:000262777300009
PM 19047403
ER
PT J
AU Wipasa, J
Xu, HJ
Liu, XQ
Hirunpetcharat, C
Stowers, A
Good, MF
AF Wipasa, Jiraprapa
Xu, Huji
Liu, Xueqin
Hirunpetcharat, Chakrit
Stowers, Anthony
Good, Michael F.
TI Effect of Plasmodium yoelii Exposure on Vaccination with the
19-Kilodalton Carboxyl Terminus of Merozoite Surface Protein 1 and Vice
Versa and Implications for the Application of a Human Malaria Vaccine
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PROTECTIVE IMMUNITY; CROSS-REACTIVITY; AOTUS MONKEYS; TH CELLS;
FALCIPARUM; FRAGMENT; MICE; IMMUNOGENICITY; ANTIBODIES; INFECTION
AB It is well known that exposure to one antigen can modulate the immune responses that develop following exposure to closely related antigens. It is also known that the composition of the repertoire can be skewed to favor epitopes shared between a current infection and a preceding one, a phenomenon referred to as "original antigenic sin." It was of interest, therefore, to investigate the antibody response that develops following exposure to the malaria vaccine candidate homologue Plasmodium yoelii MSP1(19) in mice that had previously experienced malaria infection and vice versa. In this study, preexposure of mice to Plasmodium yoelii elicited native anti-MSP1(19) antibody responses, which could be boosted by vaccination with recombinant MSP1(19). Likewise, infection of MSP1(19)-primed mice with P. yoelii led to an increase of anti-MSP1(19) antibodies. However, this increase was at the expense of antibodies to parasite determinants other than MSP1(19). This change in the balance of antibody specificities significantly affected the ability of mice to withstand a subsequent infection. These data have particular relevance to the possible outcome of malaria vaccination for those situations where the vaccine response is suboptimal and suggest that suboptimal vaccination may in fact render the ultimate acquisition of natural immunity more difficult.
C1 [Wipasa, Jiraprapa; Xu, Huji; Liu, Xueqin; Good, Michael F.] PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Wipasa, Jiraprapa] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50200, Thailand.
[Xu, Huji] Second Mil Med Univ, Changzheng Hosp, Shanghai 200003, Peoples R China.
[Hirunpetcharat, Chakrit] Mahidol Univ, Fac Publ Hlth, Dept Microbiol, Bangkok 10400, Thailand.
[Stowers, Anthony] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Good, MF (reprint author), PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
EM Huji.Xu@qimr.edu.au; Michael.Good@qimr.edu.au
FU Australian National Health and Medical Research Council; UNDP/World
Bank/ WHO Special Program for Research and Training in Tropical Diseases
(TDR); Australian NHMRC RD Wright; China MOST 973 [CB513100];
[NNSF30610103103]
FX Research in the authors' laboratories is supported by the Australian
National Health and Medical Research Council and the UNDP/World Bank/
WHO Special Program for Research and Training in Tropical Diseases
(TDR). H. X. is an Australian NHMRC RD Wright fellow, and his research
is also supported by China MOST 973 CB513100 and NNSF30610103103.
NR 19
TC 6
Z9 6
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD FEB
PY 2009
VL 77
IS 2
BP 817
EP 824
DI 10.1128/IAI.01063-08
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 399CF
UT WOS:000262777300029
PM 19015251
ER
PT J
AU Lu, ZY
Kim, W
Wilbur, WJ
AF Lu, Zhiyong
Kim, Won
Wilbur, W. John
TI Evaluation of query expansion using MeSH in PubMed
SO INFORMATION RETRIEVAL
LA English
DT Article
DE Query expansion; TREC genomics; PubMed; MeSH
ID AUTOMATIC TEXT RETRIEVAL; SUBJECT-HEADINGS MESH; LANGUAGE
AB This paper investigates the effectiveness of using MeSH (R) in PubMed through its automatic query expansion process: Automatic Term Mapping (ATM). We run Boolean searches based on a collection of 55 topics and about 160,000 MEDLINE (R) citations used in the 2006 and 2007 TREC Genomics Tracks. For each topic, we first automatically construct a query by selecting keywords from the question. Next, each query is expanded by ATM, which assigns different search tags to terms in the query. Three search tags: [MeSH Terms], [Text Words], and [All Fields] are chosen to be studied after expansion because they all make use of the MeSH field of indexed MEDLINE citations. Furthermore, we characterize the two different mechanisms by which the MeSH field is used. Retrieval results using MeSH after expansion are compared to those solely based on the words in MEDLINE title and abstracts. The aggregate retrieval performance is assessed using both F-measure and mean rank precision. Experimental results suggest that query expansion using MeSH in PubMed can generally improve retrieval performance, but the improvement may not affect end PubMed users in realistic situations.
C1 [Lu, Zhiyong; Kim, Won; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM luzh@ncbi.nlm.nih.gov
FU Intramural NIH HHS [Z99 LM999999]
NR 30
TC 58
Z9 58
U1 3
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-4564
J9 INFORM RETRIEVAL
JI Inf. Retr.
PD FEB
PY 2009
VL 12
IS 1
BP 69
EP 80
DI 10.1007/s10791-008-9074-8
PG 12
WC Computer Science, Information Systems
SC Computer Science
GA 414CZ
UT WOS:000263842800004
PM 19774223
ER
PT J
AU Dinglasan, RR
Devenport, M
Florens, L
Johnson, JR
McHugh, CA
Donnelly-Doman, M
Carucci, DJ
Yates, JR
Jacobs-Lorena, M
AF Dinglasan, R. R.
Devenport, M.
Florens, L.
Johnson, J. R.
McHugh, C. A.
Donnelly-Doman, M.
Carucci, D. J.
Yates, J. R., III
Jacobs-Lorena, M.
TI The Anopheles gambiae adult midgut peritrophic matrix proteome
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Anopheles gambiae; Peritrophic matrix; Mosquito; Proteome
ID BLOCKING MALARIA TRANSMISSION; AEDES-AEGYPTI; PLASMODIUM-GALLINACEUM;
IDENTIFICATION TECHNOLOGY; SHOTGUN PROTEOMICS; PARASITE CHITINASE;
MEMBRANE-PROTEIN; SERINE-PROTEASE; BLOOD MEAL; MOSQUITO
AB Malaria is a devastating disease. For transmission to occur, Plasmodium, the causative agent of malaria, must complete a complex developmental cycle in its mosquito vector. Thus, the mosquito is a potential target for disease control. Plasmodium ookinetes, which develop within the mosquito midgut, must first cross the midgut's peritrophic matrix (PM), a thick extracellular sheath that completely surrounds the blood meal. The PM poses a partial, natural barrier against parasite invasion of the midgut and it is speculated that modifications to the PM may lead to a complete barrier to infection. However, such strategies require thorough characterization of the structure of the PM. Here, we describe for the first time, the complete PM proteome of the main malaria vector, Anopheles gambiae. Altogether, 209 proteins were identified by mass spectrometry. Among them were nine new chitin-binding peritrophic matrix proteins, expanding the list from three to twelve peritrophins. Lastly, we provide a model for the putative interactions among the proteins identified in this study. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Dinglasan, R. R.; Devenport, M.; McHugh, C. A.; Jacobs-Lorena, M.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Florens, L.; Johnson, J. R.; Yates, J. R., III] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
[Carucci, D. J.] NIH, Grand Challenges Global Hlth Fdn, Bethesda, MD USA.
[Donnelly-Doman, M.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA.
RP Jacobs-Lorena, M (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM mlorena@jhsph.edu
OI Dinglasan, Rhoel/0000-0001-5433-8179; Dinglasan,
Rhoel/0000-0001-6563-1506; Florens, Laurence/0000-0002-9310-6650
FU NIAID; NIH [R01AI040971, 5F32AI068212]; Johns Hopkins Malaria Research
Institute; Bloomberg Family Foundation
FX This work was supported by a grant from the NIAID, NIH (R01AI040971) and
by the Johns Hopkins Malaria Research Institute and the Bloomberg Family
Foundation. R.R.D. is a NIH Ruth L Kirschstein National Research Service
Award Scholar (5F32AI068212).
NR 52
TC 56
Z9 59
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD FEB
PY 2009
VL 39
IS 2
BP 125
EP 134
DI 10.1016/j.ibmb.2008.10.010
PG 10
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 425AA
UT WOS:000264608200007
PM 19038338
ER
PT J
AU Kobey, RL
Hoshizaki, DK
Gibbs, AG
AF Kobey, R. L.
Hoshizaki, D. K.
Gibbs, A. G.
TI The Effect of Melanization on Desiccation Resistance and Thermotolerance
in Drosophila melanogaster
SO INTEGRATIVE AND COMPARATIVE BIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology
CY JAN 03-07, 2009
CL Boston, MA
SP Soc Integrat & Comparat Biol
C1 Univ Nevada, Las Vegas, NV 89154 USA.
NIDDK, NIH, Bethesda, MD 20892 USA.
EM kobeyr@unlv.nevada.edu
RI Gibbs, Allen/D-6968-2011
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 1540-7063
J9 INTEGR COMP BIOL
JI Integr. Comp. Biol.
PD FEB
PY 2009
VL 49
BP E255
EP E255
PG 1
WC Zoology
SC Zoology
GA 481KL
UT WOS:000268808801018
ER
PT J
AU Fitzpatrick, JM
Fuentes, JM
Chalmers, IW
Wynn, TA
Modolell, M
Hoffmann, KF
Hesse, M
AF Fitzpatrick, Jennifer M.
Fuentes, Jose M.
Chalmers, Iain W.
Wynn, Thomas A.
Modolell, Manuel
Hoffmann, Karl F.
Hesse, Matthias
TI Schistosoma mansoni arginase shares functional similarities with human
orthologs but depends upon disulphide bridges for enzymatic activity
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Helminth; Metabolism; Enzyme; Evolution; Adaptation; Urea; Trematode;
Drug target
ID NITRIC-OXIDE SYNTHASE; HYDROXY-L-ARGININE; HELICOBACTER-PYLORI ARGINASE;
ALTERNATIVE MACROPHAGE ACTIVATION; MULTIPLE SEQUENCE ALIGNMENT;
MAMMARY-GLAND ARGINASE; LIVER ARGINASE; MURINE MACROPHAGES; AMINO-ACIDS;
PHYSICOCHEMICAL PROPERTIES
AB Schistosome helminths constitute a major health risk for the human population in many tropical areas. We demonstrate for the first time that several developmental stages of the human parasite Schistosoma mansoni express arginase, which is responsible for the hydrolysis Of L-arginine to L-ornithine and urea. Arginase activity by alternatively activated macrophages is an essential component of the mammalian host response in schistosomiasis. However, it has not been previously shown that the parasite also expresses arginase when it is in contact with the mammalian host. After cloning and sequencing the cDNA encoding the parasite enzyme, we found that many structural features of human arginase are well conserved in the parasite ortholog. Subsequently, we discovered that S. mansoni arginase shares many similar molecular, biochemical and functional properties with both human arginase isoforms, Nevertheless, our data also reveal striking differences between human and schistosome arginase. Particularly, we found evidence that schistosome arginase activity depends upon disulphide bonds by cysteines, in contrast to human arginase. In conclusion, we report that S. mansoni arginase is well adapted to the physiological conditions that exist in the human host. (c) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Hesse, Matthias] Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, Ithaca, NY 14853 USA.
[Fitzpatrick, Jennifer M.; Chalmers, Iain W.; Hoffmann, Karl F.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Fuentes, Jose M.] Univ Extremadura, CIBER Enfermedades Neurodegenerat, Dept Bioquim & Biol Mol & Genet, EU Enfermeria & TO, Caceres, Spain.
[Wynn, Thomas A.; Hesse, Matthias] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Modolell, Manuel] Max Planck Inst Immunobiol, D-7800 Freiburg, Germany.
RP Hesse, M (reprint author), Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, VMC C5 147, Ithaca, NY 14853 USA.
EM mh325@cornell.edu
RI Greenberg, Robert/D-1091-2009; Wynn, Thomas/C-2797-2011; Fuentes,
Jose/H-9490-2014
OI Fuentes, Jose/0000-0001-6910-2089
FU Uunta de Extremadura [PR106B124]; ISCIII [PR106B124]; Wellcome Trust
[RG35177, RG35522]
FX We thank Dr. Fred Lewis and his colleagues at the Biomedical Research
Institute (Rockville, MD) for providing parasite material used in this
study. We further thank Mary Leusink (LPD, Bethesda, MD) and Fae
Tompkins (Cornell University, Ithaca, NY) for technical assistance.
Funding was provided by grants PR106B124 Uunta de Extremadura) and
P1070400 (FIS, ISCIII, MSQ to JM Fuentes and KF Hoffmann is Supported by
grants received from the Wellcome Trust (RG35177 and RG35522).
NR 96
TC 10
Z9 10
U1 2
U2 5
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 FEB
PY 2009
VL 39
IS 3
BP 267
EP 279
DI 10.1016/j.ijpara.2008.06.015
PG 13
WC Parasitology
SC Parasitology
GA 412FQ
UT WOS:000263710000001
PM 18723022
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Evolution of genome architecture
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Review
DE Positive selection; Purifying selection; Recombination; Operons; Gene
clustering
ID HUMAN TRANSCRIPTOME MAP; GENE CLUSTERS; NEIGHBORING GENES; PROKARYOTIC
GENOMES; SELFISH OPERONS; EXPRESSED GENES; CAENORHABDITIS-ELEGANS;
COMPUTATIONAL ANALYSIS; TRANSPOSABLE ELEMENTS; SPLICEOSOMAL INTRONS
AB Charles Darwin believed that all traits of organisms have been honed to near perfection by natural selection. The empirical basis underlying Darwin's conclusions consisted of numerous observations made by him and other naturalists on the exquisite adaptations of animals and plants to their natural habitats and on the impressive results of artificial selection. Darwin fully appreciated the importance of heredity but was unaware of the nature and, in fact, the very existence of genomes. A century and a half after the publication of the "Origin", we have the opportunity to draw conclusions from the comparisons of hundreds of genome sequences from all walks of life. These comparisons suggest that the dominant mode of genome evolution is quite different from that of the phenotypic evolution. The genomes of vertebrates, those purported paragons of biological perfection, turned out to be veritable junkyards of selfish genetic elements where only a small fraction of the genetic material is dedicated to encoding biologically relevant information. In sharp contrast, genomes of microbes and viruses are incomparably more compact, with most of the genetic material assigned to distinct biological functions. However, even in these genomes, the specific genome organization (gene order) is poorly conserved. The results of comparative genomics lead to the conclusion that the genome architecture is not a straightforward result of continuous adaptation but rather is determined by the balance between the selection pressure, that is itself dependent on the effective population size and mutation rate, the level of recombination, and the activity of selfish elements. Although genes and, in many cases, multigene regions of genomes possess elaborate architectures that ensure regulation of expression, these arrangements are evolutionarily volatile and typically change substantially even on short evolutionary scales when gene sequences diverge minimally. Thus, the observed genome architectures are, mostly, products of neutral processes or epiphenomena of more general selective processes, such as selection for genome streamlining in successful lineages with large populations. Selection for specific gene arrangements (elements of genome architecture) seems only to modulate the results of these processes. Published by Elsevier Ltd
C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU DHHS (National Library of Medicine)
FX I thank Pavel Novichkov for providing the data for Fig. 3. The author's
research is supported by the DHHS (National Library of Medicine)
intramural funds.
NR 116
TC 76
Z9 78
U1 4
U2 39
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD FEB
PY 2009
VL 41
IS 2
BP 298
EP 306
DI 10.1016/j.biocel.2008.09.015
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 399IF
UT WOS:000262792900008
PM 18929678
ER
PT J
AU Meijer, CJLM
Berkhof, J
Castle, PE
Hesselink, AT
Franco, EL
Ronco, G
Arbyn, M
Bosch, FX
Cuzick, J
Dillner, J
Heideman, DAM
Snijders, PJF
AF Meijer, Chris J. L. M.
Berkhof, Johannes
Castle, Philip E.
Hesselink, Albertus T.
Franco, Eduardo L.
Ronco, Guglielmo
Arbyn, Marc
Bosch, F. Xavier
Cuzick, Jack
Dillner, Joakim
Heideman, Danielle A. M.
Snijders, Peter J. F.
TI Guidelines for human papillomavirus DNA test requirements for primary
cervical cancer screening in women 30 years and older
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HPV-DNA testing; cervical screening; HPV test guidelines; HPV test
requirements; HPV test statistics
ID RANDOMIZED CONTROLLED-TRIAL; POLYMERASE-CHAIN-REACTION; RISK
HUMAN-PAPILLOMAVIRUS; LIQUID-BASED CYTOLOGY; INTRAEPITHELIAL NEOPLASIA;
HYBRID CAPTURE-2; BASE-LINE; HYBRID-CAPTURE-2; RECRUITMENT; MANAGEMENT
AB Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. (C) 2008 Wiley-Liss, Inc.
C1 [Meijer, Chris J. L. M.; Hesselink, Albertus T.; Heideman, Danielle A. M.; Snijders, Peter J. F.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands.
[Berkhof, Johannes] Vrije Univ Amsterdam, Med Ctr, Dept Clin Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.
[Castle, Philip E.] NIH, Dept Canc Epidemiol & Genet, Washington, DC USA.
[Franco, Eduardo L.] McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada.
[Ronco, Guglielmo] Ctr Prevenz Oncol, Canc Epidemiol Unit, Turin, Italy.
[Arbyn, Marc] Sci Inst Publ Hlth, Canc Epidemiol Unit, Brussels, Belgium.
[Arbyn, Marc] IARC, ECCG European Cooperat Dev & Implementat Canc Scr, Lyon, France.
[Bosch, F. Xavier] Hosp Ilobregat, ICO, Serv Epidemiol, Barcelona, Spain.
[Cuzick, Jack] Barts & London Queen Marys Sch Med & Dent, London, England.
[Dillner, Joakim] Lund Univ, Univ Hosp, Dept Med Microbiol, Malmo, Sweden.
[Cuzick, Jack] Canc Res UK, London, England.
RP Meijer, CJLM (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Pathol, POB 7057, NL-1007 MB Amsterdam, Netherlands.
EM cjlm.meijer@vumc.nl
RI Arbyn, Marc/B-6887-2009; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012;
OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Franco,
Eduardo/0000-0002-4409-8084
FU Intramural NIH HHS [Z99 CA999999]
NR 34
TC 247
Z9 253
U1 1
U2 12
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 1
PY 2009
VL 124
IS 3
BP 516
EP 520
DI 10.1002/ijc.24010
PG 5
WC Oncology
SC Oncology
GA 391AS
UT WOS:000262205400002
PM 18973271
ER
PT J
AU Castillejo, A
Rothman, N
Murta-Nascimento, C
Malats, N
Garcia-Closas, M
Gomez-Martinez, A
Lloreta, J
Tardon, A
Serra, C
Garcia-Closas, R
Chanock, S
Silverman, DT
Dosemeci, M
Kogevinas, M
Carrato, A
Soto, JL
Real, FX
AF Castillejo, Adela
Rothman, Nathaniel
Murta-Nascimento, Cristiane
Malats, Nuria
Garcia-Closas, Montserrat
Gomez-Martinez, Angeles
Lloreta, Josep
Tardon, Adonina
Serra, Consol
Garcia-Closas, Reina
Chanock, Stephen
Silverman, Debra T.
Dosemeci, Mustafa
Kogevinas, Manolis
Carrato, Alfredo
Soto, Jose Luis
Real, Francisco X.
TI TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer
risk and prognosis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE urinary bladder cancer; genetic susceptibility; transforming growth
factor beta; transforming growth factor-beta receptor; prognosis;
survival; recurrence; progression
ID GROWTH-FACTOR-BETA; GENE POLYMORPHISMS; TGF-BETA-1 GENE; ASSOCIATION;
TGFBR1-ASTERISK-6A; DISEASE; SUSCEPTIBILITY; METAANALYSIS; CARCINOMA
AB The transforming growth factor-beta (TGF-beta) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF-beta signalling pathway (TGFBI and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFBI (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case-control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan-Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle-invasive tumors, we found a significant association between TGFBR1-rs868 and disease-specific mortality with an allele dosage effect (p-trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1-rs868 with outcome should be validated in independent patient series. (C) 2008 Wiley-Liss, Inc.
C1 [Castillejo, Adela; Gomez-Martinez, Angeles; Carrato, Alfredo; Soto, Jose Luis] Hosp Gen Univ Elche, Mol Oncol Grp, Elche, Spain.
[Rothman, Nathaniel; Garcia-Closas, Montserrat; Silverman, Debra T.; Dosemeci, Mustafa] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Murta-Nascimento, Cristiane; Malats, Nuria; Kogevinas, Manolis; Real, Francisco X.] IMIM Hosp del Mar, Inst Municipal Invest Med, Programa Recerca Canc, Barcelona, Spain.
[Murta-Nascimento, Cristiane; Malats, Nuria; Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Malats, Nuria; Real, Francisco X.] CNIO, Programa Genet Canc Humano, E-28029 Madrid, Spain.
[Malats, Nuria; Real, Francisco X.] CNIO, Programa Patol Mol, E-28029 Madrid, Spain.
[Lloreta, Josep] Hosp del Mar, Dept Patol, Barcelona, Spain.
[Lloreta, Josep; Serra, Consol; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Tardon, Adonina] Univ Oviedo, Dept Epidemiol & Prevent Med, Oviedo, Spain.
[Tardon, Adonina; Kogevinas, Manolis] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, Dept Social Med, San Cristobal la Laguna, Spain.
[Kogevinas, Manolis] Univ Crete, Iraklion, Greece.
[Chanock, Stephen] NCI, Core Genotype Facil, Adv Technol Ctr, Gaithersburg, MD USA.
RP Real, FX (reprint author), CNIO, Programa Genet Canc Humano, C Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
EM preal@cnio.es
RI Murta-Nascimento, Cristiane/G-3738-2012; Serra, C/E-6879-2014; Lloreta,
J/I-2112-2014; Benavides, Fernando/A-5137-2008; Garcia-Closas,
Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Kogevinas,
Manolis/C-3918-2017; Real, Francisco X/H-5275-2015
OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; Benavides,
Fernando/0000-0003-0747-2660; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Soto, Jose
Luis/0000-0003-0234-9188; Real, Francisco X/0000-0001-9501-498X
FU Fondo de Investigacion Sanitaria, Spain [00/0745, G03/174, PI051436,
PI061614]; Fundacio La Marato de TV3; National Cancer Institute, USA
FX Grant sponsor: Fondo de Investigacion Sanitaria, Spain: Grant numbers:
00/0745, G03/174. PI051436, PI061614; Grant sponsors: Fundacio La Marato
de TV3, National Cancer Institute. USA.
NR 24
TC 29
Z9 31
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 1
PY 2009
VL 124
IS 3
BP 608
EP 613
DI 10.1002/ijc.24013
PG 6
WC Oncology
SC Oncology
GA 391AS
UT WOS:000262205400013
PM 19004027
ER
PT J
AU Birmann, BM
Breen, EC
Stuver, S
Cranston, B
Martinez-Maza, O
Falk, KI
Okayama, A
Hanchard, B
Mueller, N
Hisada, M
AF Birmann, Brenda M.
Breen, Elizabeth C.
Stuver, Sherri
Cranston, Beverly
Martinez-Maza, Otoniel
Falk, Kerstin I.
Okayama, Akihiko
Hanchard, Barrie
Mueller, Nancy
Hisada, Michie
TI Population differences in immune marker profiles associated with human
T-lymphotropic virus type I infection in Japan and Jamaica
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HTLV-I; epidemiology; natural history; host immunity; viral markers
ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; CIRCULATING INTERLEUKIN-6
LEVELS; CELL LEUKEMIA ATL; HTLV-I; HEALTHY CARRIERS; PROVIRAL LOAD;
CD8(+) CELLS; ANTIBODY; ACTIVATION; PATTERNS
AB The natural history of human T-lymphotropic virus type I (HTLV-1) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-1 non-carriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 7 1, respectively, p = 0.005), soluble interleukin-2 receptor-a (477 vs. 623 pg/mL, p = 0.0008) and soluble CD30 (34 vs. 46 U/mL, p = 0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 mu g/mL, p = 0.0004). HTLV-1 infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-1 carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk. (C) 2008 Wiley-Liss, Inc.
C1 [Birmann, Brenda M.; Stuver, Sherri; Mueller, Nancy] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Breen, Elizabeth C.; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Stuver, Sherri] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Cranston, Beverly; Hanchard, Barrie] Univ W Indies, Dept Pathol, Kingston 7, Jamaica.
[Falk, Kerstin I.] Karolinska Inst, Ctr Microbiol Preparedness, Swedish Inst Infect Dis Control, Stockholm, Sweden.
[Falk, Kerstin I.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Okayama, Akihiko] Miyazaki Univ, Dept Lab Med, Miyazaki Med Coll, Miyazaki, Japan.
[Hisada, Michie] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Birmann, BM (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM brenda.birmann@channing.harvard.edu
RI Martinez-Maza, Otoniel/B-2667-2009;
OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Stuver,
Sherri/0000-0002-4027-2663
FU Public Health Service [CA115687, CA38450, CA09001]; Intramural Research
Program of the National Institutes of Health; National Cancer Institute.
Division of Cancer Epidemiology and Genetics
FX Grant sponsor: Public Health Service: Grant numbers: CA115687, CA38450,
CA09001. Grant sponsors: Intramural Research Program of the National
Institutes of Health, National Cancer Institute. Division of Cancer
Epidemiology and Genetics.
NR 45
TC 12
Z9 12
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 1
PY 2009
VL 124
IS 3
BP 614
EP 621
DI 10.1002/ijc.24012
PG 8
WC Oncology
SC Oncology
GA 391AS
UT WOS:000262205400014
PM 18989900
ER
PT J
AU Patlolla, AK
Barnes, C
Hackett, D
Tchounwou, PB
AF Patlolla, Anita K.
Barnes, Constance
Hackett, Diahanna
Tchounwou, Paul B.
TI Potassium Dichromate Induced Cytotoxicity, Genotoxicity and Oxidative
Stress in Human Liver Carcinoma (HepG(2)) Cells
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE HepG2 cells; cytotoxicity; DNA damage; lipid peroxidation;
malondialdehyde; potassium dichromate
ID DNA-DAMAGE; HEXAVALENT CHROMIUM; LIPID-PEROXIDATION; CARCINOGENICITY;
ANTIOXIDANTS; MECHANISMS; TOXICITY; CR(VI); RATS; MICE
AB Chromium is a widespread industrial waste. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized to act as a carcinogen, mutagen and teratogen towards humans and animals. The fate of chromium in the environment is dependent on its oxidation state. Hexavalent chromium primarily enters the cells and undergoes metabolic reduction to trivalent chromium, resulting in the formation of reactive oxygen species together with oxidative tissue damage and a cascade of cellular events. However, the results from in vitro studies are often conflicting. The aim of this study was to develop a model to establish relationships between cytotoxicity, genotoxicity and oxidative stress, in human liver carcinoma [HepG2] cells exposed to potassium dichromate. HepG2 cells were cultured following standard protocols and exposed to various concentrations [0-50 mu M] of potassium dichromate [K(2)Cr(2)O(7)]. Following exposure to the toxic metal, the MTT assay was performed to assess the cytotoxicity, the thiobarbituric acid test to evaluate the degree of lipid peroxidation as an indicator of oxidative stress and the alkaline comet assay was used to assess DNA damage to study genotoxicity. The results of the study indicated that potassium dichromate was cytotoxic to HepG2 cells. The LD(50) values of 8.83 +/- 0.89 mu g/ml, 6.76 +/- 0.99 mu g/ml, respectively, for cell mortality at 24 and 48 hrs were observed, indicating a dose- and time-dependent response with regard to the cytotoxic effects of potassium dichromate. A statistically significant increase in the concentration of malondialdehyde [MDA], an indicator of lipid peroxidation, was recorded in exposed cells [15.9 - 69.9 mu M] compared to control [13 mu M]. Similarly, a strong dose-response relationship (p<0.05) was also obtained with respect to potassium dichromate induced DNA damage (comet assay) in HepG2 cells exposed [3.16 +/- 0.70 - 24.84 +/- 1.86 microns - mean comet tail length]; [12.4 +/- 1.45% - 76 +/- 1.49% - % tail DNA] to potassium dichromate than control [3.07 +/- 0.26 microns - mean comet tail length]; [2.69 + 0.19% - % Tail DNA], respectively. The results demonstrated that potassium dichromate was highly cytotoxic to HepG2 cells, and its cytotoxicity seems to be mediated by oxidative stress and DNA damage.
C1 [Patlolla, Anita K.; Barnes, Constance; Hackett, Diahanna; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,CSET, Jackson, MS USA.
RP Patlolla, AK (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,CSET, Jackson, MS USA.
EM anita.k.patlolla@jsums.edu; constancepb@yahoo.com;
diahanna.m.hackett@jsums.edu; paul.b.tchounwou@jsums.edu
FU National Institutes of Health [1G12RR13459]
FX This research was financially supported by a grant from the National
Institutes of Health - (Grant No 1G12RR13459), through the RCMI-Center
for Environmental Health at Jackson State University.. The authors thank
Dr. Abdul K. Mohamed, Dean Emeritus, and the RCMI external advisory
committee members, for their technical support in this project.
NR 38
TC 32
Z9 34
U1 0
U2 13
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 FEB
PY 2009
VL 6
IS 2
BP 643
EP 653
DI 10.3390/ijerph6020643
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 451BI
UT WOS:000266445300017
PM 19440407
ER
PT J
AU Burton, PR
Hansell, AL
Fortier, I
Manolio, TA
Khoury, MJ
Little, J
Elliott, P
AF Burton, Paul R.
Hansell, Anna L.
Fortier, Isabel
Manolio, Teri A.
Khoury, Muin J.
Little, Julian
Elliott, Paul
TI Size matters: just how big is BIG? Quantifying realistic sample size
requirements for human genome epidemiology
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Human genome epidemiology; biobank; sample size; statistical power;
simulation studies; measurement error; reliability; aetiological
heterogeneity
ID GENE-DISEASE ASSOCIATIONS; FACTOR-H POLYMORPHISM; WIDE ASSOCIATION;
MENDELIAN RANDOMIZATION; MACULAR DEGENERATION; COMPLEX DISEASES; COMMON
DISEASES; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER; PROSTATE-CANCER
AB Background Despite earlier doubts, a string of recent successes indicates that if sample sizes are large enough, it is possible-both in theory and in practice-to identify and replicate genetic associations with common complex diseases. But human genome epidemiology is expensive and, from a strategic perspective, it is still unclear what 'large enough' really means. This question has critical implications for governments, funding agencies, bioscientists and the tax-paying public. Difficult strategic decisions with imposing price tags and important opportunity costs must be taken.
Methods Conventional power calculations for case-control studies disregard many basic elements of analytic complexity-e. g. errors in clinical assessment, and the impact of unmeasured aetiological determinants-and can seriously underestimate true sample size requirements. This article describes, and applies, a rigorous simulation-based approach to power calculation that deals more comprehensively with analytic complexity and has been implemented on the web as ESPRESSO: (www.p3gobservatory.org/powercalculator.htm).
Results Using this approach, the article explores the realistic power profile of stand-alone and nested case-control studies in a variety of settings and provides a robust quantitative foundation for determining the required sample size both of individual biobanks and of large disease-based consortia. Despite universal acknowledgment of the importance of large sample sizes, our results suggest that contemporary initiatives are still, at best, at the lower end of the range of desirable sample size. Insufficient power remains particularly problematic for studies exploring gene-gene or gene-environment interactions.
Discussion Sample size calculation must be both accurate and realistic, and we must continue to strengthen national and international cooperation in the design, conduct, harmonization and integration of studies in human genome epidemiology.
C1 [Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Burton, Paul R.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Burton, Paul R.; Fortier, Isabel; Khoury, Muin J.; Little, Julian] Univ Montreal, P3G, Montreal, PQ H3C 3J7, Canada.
[Hansell, Anna L.; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England.
[Fortier, Isabel] Univ Montreal, Dept Med Sociale & Prevent, Montreal, PQ, Canada.
[Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA.
[Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada.
RP Burton, PR (reprint author), Univ Leicester, Dept Hlth Sci, Adrian Bldg,Room 217,Univ Rd, Leicester LE1 7RH, Leics, England.
EM pb51@le.ac.uk
RI Burton, Paul/H-7527-2016
FU UK Biobank; Wellcome Trust; Medical Research Council; Department of
Health; Scottish Executive and Northwest Regional Development Agency;
European Union under the Framework 6 program; Wellcome Trust
Intermediate Clinical Fellow [075883]
FX We gratefully acknowledge the support of the steering committee of UK
Biobank in encouraging and discussing the implications of this research.
Initial power calculations were funded by UK Biobank from its joint
funders: Wellcome Trust, Medical Research Council, Department of Health,
Scottish Executive and Northwest Regional Development Agency. This work
was also supported as a central element of the research programmes of P
3 G ( the Public Population Project in Genomics) funded by Genome Canada
and Genome Quebec, and PHOEBE ( Promoting Harmonization of
Epidemiological Biobanks in Europe) funded by the European Union under
the Framework 6 program. A. L. H. is a Wellcome Trust Intermediate
Clinical Fellow ( grant number 075883). J.L. is a Canada Research Chair
in Human Genome Epidemiology. The programme of methods research in
genetic epidemiology in Leicester is funded in part by MRC Cooperative
Grant G9806740. We wish to thank those who kindly provided us with
advice and data: Gabriele Nagel, Sabine Rohrman, Bertrand Hemon, Paolo
Vineis [ European Prospective Investigation of Cancer and Nutrition (
EPIC)]; Peter Rothwell ( Stroke Prevention Research Unit, Radcliffe
Infirmary, Oxford); Joan Soriano, GlaxoSmithKline ( for estimates of UK
COPD incidence) and the UK Small Area Health Statistics Unit, Imperial
College London.
NR 79
TC 117
Z9 120
U1 4
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2009
VL 38
IS 1
BP 263
EP 273
DI 10.1093/ije/dyn147
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 404PB
UT WOS:000263164400035
PM 18676414
ER
PT J
AU Tuan, RS
AF Tuan, Rocky S.
TI Chondroregulatory signals in osteoarthritis
SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
LA English
DT Meeting Abstract
CT Annual General Meeting of the British-Society-for-Matrix-Biology
CY APR 07-08, 2008
CL York Univ, York, ENGLAND
SP British Soc Matrix Biol
HO York Univ
C1 [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Tuan, Rocky S.] NIH, Bethesda, MD 20892 USA.
EM tuanr@mail.nih.gov
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 0959-9673
J9 INT J EXP PATHOL
JI Int. J. Exp. Pathol.
PD FEB
PY 2009
VL 90
IS 1
BP A51
EP A51
PG 1
WC Pathology
SC Pathology
GA 395HW
UT WOS:000262516200023
ER
PT J
AU Teufel, A
Maass, T
Galle, PR
Malik, N
AF Teufel, Andreas
Maass, Thorsten
Galle, Peter R.
Malik, Nasir
TI The longevity assurance homologue of yeast lag1 (Lass) gene family
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Review
DE longevity; homeodomain; ceramide; cancer; apoptosis; stress response
ID CERAMIDE SYNTHESIS; CANCER-THERAPY; CELL-DEATH; SYNTHASE; PROTEINS; COA;
DOMAINS; MEMBERS; HOX; METABOLISM
AB The Lass gene family contains a group of highly conserved genes that are found in eukaryotic species. The founding member. lag1. was discovered in a screen for yeast longevity genes. Subsequently, lag1 homologs were discovered in other organisms including six mammalian paralogs. All Lass genes encode a highly conserved Lag1 domain and many also have an additional Hox domain. Lass proteins are ceramide synthases and therefore are critical for ceramide biosynthesis. Ceramide synthase is also a critical enzyme in the sphingolipid biosynthetic pathway. As ceramide and sphingolipids are key intermediates in diverse cellular processes such as cell growth, apoptosis, and stress response and may also play a role in cancer development, the function of Lass proteins is of great interest. In this review, we summarize the state of knowledge regarding Lass protein structure, biological function, and their emerging role in cancer development.
C1 [Teufel, Andreas; Maass, Thorsten; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med, D-55101 Mainz, Germany.
[Malik, Nasir] NIDA, Cellular Neurobiol Branch, NIH, Baltimore, MD USA.
RP Teufel, A (reprint author), Johannes Gutenberg Univ Mainz, Dept Internal Med 1, Bldg 605,Langenbeckstr 1, D-55101 Mainz, Germany.
EM teufel@uni-mainz.de
NR 36
TC 28
Z9 28
U1 0
U2 2
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD FEB
PY 2009
VL 23
IS 2
BP 135
EP 140
DI 10.3892/ijmm_00000110
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 396DD
UT WOS:000262571500001
PM 19148536
ER
PT J
AU Schlett, CL
Massaro, JM
Lehman, SJ
Bamberg, F
O'Donnell, CJ
Fox, CS
Hoffmann, U
AF Schlett, C. L.
Massaro, J. M.
Lehman, S. J.
Bamberg, F.
O'Donnell, C. J.
Fox, C. S.
Hoffmann, U.
TI Novel measurements of periaortic adipose tissue in comparison to
anthropometric measures of obesity, and abdominal adipose tissue
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE adipose tissue; intra-abdominal fat; tomography; spiral computed;
Framingham Heart Study; metabolic risk factors
ID CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY; RISK-FACTORS;
CARDIOVASCULAR-DISEASE; PERIADVENTITIAL FAT; PERICARDIAL FAT; EPICARDIAL
FAT; HEART-FAILURE; MEN; ATHEROSCLEROSIS
AB Background: Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.
Methods: Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n = 100) who underwent multidetector CT of the thorax (ECG triggering, 2.5mm slice thickness) and the abdomen (helical CT acquisition, 2.5mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between -195 and -45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.
Results: The intra-and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra-and inter-observer difference was small for both AAT (-1.85 +/- 1.28% and 7.85 +/- 6.08%; respectively) and TAT (3.56 +/- 0.83% and -4.56 +/- 0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r = 0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r = 0.39 and 0.42, P<0.0001 and P = 0.009), waist circumference (r = 0.49 and 0.57, P<0.0001 for both) and body mass index (r = 0.47 and 0.58, P<0.0001 for both).
Conclusion: Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes.
C1 [Schlett, C. L.; Lehman, S. J.; Bamberg, F.; Hoffmann, U.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Massaro, J. M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[O'Donnell, C. J.; Fox, C. S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[O'Donnell, C. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA.
[Fox, C. S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02114 USA.
RP Hoffmann, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart, Lung and Blood Institute [N01-HC-25195]; German Federal
Ministry of Education and Research; Foundation of German Business,
Berlin
FX The Framingham Heart Study is supported by the National Heart, Lung and
Blood Institute (N01-HC-25195). CL Schlett is supported in part by
grants from the German Federal Ministry of Education and Research and
the Foundation of German Business, Berlin.
NR 31
TC 44
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U1 0
U2 1
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 FEB
PY 2009
VL 33
IS 2
BP 226
EP 232
DI 10.1038/ijo.2008.267
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 407JU
UT WOS:000263360200006
PM 19139753
ER
PT J
AU Eiriksdottir, G
Smith, AV
Aspelund, T
Hafsteinsdottir, SH
Olafsdottir, E
Launer, LJ
Harris, TB
Gudnason, V
AF Eiriksdottir, G.
Smith, A. V.
Aspelund, T.
Hafsteinsdottir, S. H.
Olafsdottir, E.
Launer, L. J.
Harris, T. B.
Gudnason, V.
TI The interaction of adiposity with the CRP gene affects CRP levels: Age,
Gene/Environment Susceptibilty-Reykjavik Study
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE CRP gene; CRP levels; adiposity; gene/environment interaction;
AGES-Reykjavik Study
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; TYPE-2 DIABETES-MELLITUS;
BODY-FAT DISTRIBUTION; METABOLIC-SYNDROME; MYOCARDIAL-INFARCTION;
POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; RISK; POLYMORPHISMS
AB Objective: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels.
Methods: The first 2296 participants (mean age 76 +/- 6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10mgl(-1)) in men and women separately.
Results: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P = 0.045) and waist circumference (P = 0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization.
Conclusions: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele.
C1 [Eiriksdottir, G.; Smith, A. V.; Aspelund, T.; Hafsteinsdottir, S. H.; Olafsdottir, E.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, T.] Univ Iceland, Dept Math, Reykjavik, Iceland.
[Gudnason, V.] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Launer, L. J.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Eiriksdottir, G (reprint author), Hjartavernd Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland.
EM gudny@hjarta.is
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845
FU National Institutes of Health [N01-AG-12100]; National Institute on
Aging Intramural Research Program, Hjartavernd; Althingi
FX This study was funded by National Institutes of Health contract
N01-AG-12100, the National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association) and the Althingi
(the Icelandic Parliament).
NR 36
TC 19
Z9 19
U1 0
U2 2
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 FEB
PY 2009
VL 33
IS 2
BP 267
EP 272
DI 10.1038/ijo.2008.274
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 407JU
UT WOS:000263360200011
PM 19139754
ER
PT J
AU Moreira, EF
Larrayoz, IM
Lee, JW
Rodriguez, IR
AF Moreira, Ernesto F.
Larrayoz, Ignacio M.
Lee, Jung Wha
Rodriguez, Ignacio R.
TI 7-Ketocholesterol Is Present in Lipid Deposits in the Primate Retina:
Potential Implication in the Induction of VEGF and CNV Formation
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; LOW-DENSITY-LIPOPROTEIN; LIVER-X-RECEPTORS;
NF-KAPPA-B; FACTOR GENE; IN-VITRO; ATHEROSCLEROTIC PLAQUES;
BIOLOGICAL-SYSTEMS; EPITHELIAL-CELLS; BRUCHS MEMBRANE
AB PURPOSE. 7-Ketocholesterol is a highly toxic oxysterol found in abundance in atherosclerotic plaques and is believed to play a critical role in atherosclerosis. The purpose of this study was to identify and localize 7-ketocholesterol (7kCh) in the primate retina and to examine the potential consequences of its presence in oxidized lipid deposits in the retina.
METHODS. Unsterified 7kCh was identified and quantified by high-performance liquid chromatography-mass spectrometry. Localization of 7kCh was performed by immunohistochemistry. VEGF induction was determined by qRT-PCR. Cell viability was determined by measuring cellular dehydrogenase activity. Analyses were performed using ARPE19 and human vascular endothelial cells (HMVECs).
RESULTS. 7-Ketocholesterol is localized mainly to deposits in the choriocapillaris and Bruch's membrane and on the surfaces of vascular endothelial cells of the neural retina. RPE/choriocapillaris regions contained approximately four times more 7kCh than the neural retina. In ARPE19 cells and HMVECs, oxidized LDL and 7kCh induced VEGF 8- to 10-fold above controls. Hypoxia inducible factor (HIF)-1 alpha levels did not increase as a result of 7kCh treatment, suggesting an HIF-independent induction pathway. Cholesterol sulfate, a liver X receptor (LXR) antagonist, had marked attenuation of the 7kCh-mediated VEGF induction. LXR-specific siRNAs also reduced VEGF induction. Inhibition of NF-kappa B with BAY 11-7082 reduced IL-8 but not VEGF induction.
CONCLUSIONS. The location of 7-kCh in the retina and its induction of VEGF in cultured RPE cells and HMVECs suggest it may play a critical role in choroidal neovascularization. The pathway for VEGF induction seems to be independent of HIF-1 alpha and NF-kappa B but seems to be partially regulated by LXRs. (Invest Ophthalmol Vis Sci. 2009;50:523-532) DOI:10.1167/iovs.08-2373
C1 [Rodriguez, Ignacio R.] NEI, NIH, Sect Mech Retinal Dis, LRCMB, Bethesda, MD 20892 USA.
RP Rodriguez, IR (reprint author), NEI, NIH, Sect Mech Retinal Dis, LRCMB, 7 Mem Dr,MSC0706,Bldg 7,Room 302, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
RI Larrayoz, Ignacio/I-5613-2012
OI Larrayoz, Ignacio/0000-0003-1629-152X
FU National Eye Institute
FX Supported by the National Eye Institute Intramural Research Program.
NR 45
TC 46
Z9 46
U1 0
U2 6
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 FEB
PY 2009
VL 50
IS 2
BP 523
EP 532
DI 10.1167/iovs.08-2373
PG 10
WC Ophthalmology
SC Ophthalmology
GA 397MD
UT WOS:000262665900005
PM 18936140
ER
PT J
AU Koonin, EV
Novozhilov, AS
AF Koonin, Eugene V.
Novozhilov, Artem S.
TI Origin and Evolution of the Genetic Code: The Universal Enigma
SO IUBMB LIFE
LA English
DT Review
DE genetic code; translation; evolution
ID TRANSFER-RNA IDENTITY; PROTEIN AMINO-ACIDS; ERROR MINIMIZATION;
COEVOLUTION THEORY; TRIPLET-CODE; COMPARATIVE GENOMICS; TRANSLATION
SYSTEM; FROZEN ACCIDENT; SELECTION; ALPHABET
AB The genetic code is nearly universal, and the arrangement or the codons in the standard codon table is highly nonrandom. The three main concepts on the origin and evolution of the code are the stereochemical theory, according to which codon assignments are dictated by physicochemical affinity between amino acids and the cognate codons (anticodons); the coevolution theory, which posits that the code structure coevolved with amino acid biosynthesis pathways; and the error minimization theory under which selection to minimize the adverse effect or point mutations anti translation errors was the principal factor of the code's evolution. These theories are not. mutually exclusive and are also compatible with the frozen accident hypothesis, that is, the notion that the standard code might have no special properties but was fixed simply because all extant life forms share a common ancestor, with subsequent changes to the code, mostly, precluded by the deleterious effect of codon reassignment. Mathematical analysis of the structure and possible evolutionary trajectories of the code shows that it is highly robust to translational misreading but there are numerous more robust codes, so the standard code potentially could evolve from a random code via a short sequence of codon seriesreassignments. Thus, much of the evolution that led to the standard code could be a combination of frozen accident with selection for error minimization although contributions from coevolution of the code with metabolic pathways and weak affinities between amino acids and nucleotide triplets cannot be ruled out. However, such scenarios for the code evolution are based on formal schemes whose relevance to the actual primordial evolution is uncertain. A real understanding of the code origin and evolution is likely to be attainable only in conjunction with a credible scenario for the evolution of the coding principle itself and the translation system. (c) 2008 IUBMB
C1 [Koonin, Eugene V.; Novozhilov, Artem S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013
OI Novozhilov, Artem/0000-0001-5469-2557
FU Aspen Center for Physics (Aspen, CO) [8/10/2008-8/31/2008]; Department
of Health and Human Services intramural program (NIH, National Library
of Medicine)
FX Although the study of the evolution of the genetic code is a relatively
well-focused field, the literature accumulated over the 50 years of
research is extensive, and we could not possibly cover all of it in a
brief review article. Our sincere apologies to all colleagues whose
relevant work is not cited because of space restrictions. EVK is
grateful to Nigel Goldenfeld, Paul Higgs, and Claus Wilke for insightful
discussions during the workshop on "Evolution: from Atoms to Organisms"
at the Aspen Center for Physics (Aspen, CO), 8/10/2008-8/31/2008. The
authors' research is supported by the Department of Health and Human
Services intramural program (NIH, National Library of Medicine).
NR 140
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U2 51
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1521-6543
J9 IUBMB LIFE
JI IUBMB Life
PD FEB
PY 2009
VL 61
IS 2
BP 99
EP 111
DI 10.1002/iub.146
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 403HX
UT WOS:000263074800003
PM 19117371
ER
PT J
AU Hartley, T
Stewart, C
Stewart, R
Munroe, DJ
AF Hartley, Todd
Stewart, Claudia
Stewart, Robin
Munroe, David J.
TI Cost-Effective Addition of High-Throughput Colony Picking Capability to
a Standard Liquid-Handling Platform
SO JALA
LA English
DT Article
DE colony picking; liquid; ALH 3000
AB We have developed a general strategy for the addition of high-throughput colony picking capability to most standard liquid-handling robotic platform This strategy is easily implemented and requires minimal capital outlay (less than $2500 00) To illustrate this strategy, we describe the modification of a Caliper Life Sciences Sciclone ALH (Automated Liquid Handler) 3000 together with a general calibration methodology that can be applied to most liquid-handling robot capable of X, Y, Z positioning (JALA 2009,14 22-26)
C1 [Hartley, Todd; Stewart, Claudia; Stewart, Robin; Munroe, David J.] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
RP Hartley, T (reprint author), Lab Mol Technol, 915 Tollhouse Ave,Suite 209, Frederick, MD 21701 USA.
FU National Cancer Institute National Institutes of Health [N01 CO-12400]
FX This project has been funded in whole or in port with federal funds from
the National Cancer Institute National Institutes of Health under
contract N01 CO-12400 The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services nor does mention of trade names commercial products
or organizations imply endorsement by the U S Government
NR 2
TC 4
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U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1535-5535
J9 JALA-J ASSOC LAB AUT
JI JALA
PD FEB
PY 2009
VL 14
IS 1
BP 22
EP 26
DI 10.1016/j.jala.2008.03.004
PG 5
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 691HO
UT WOS:000285071100005
ER
PT J
AU Jennings, JM
Ellen, JM
Deeds, BG
Harris, DR
Muenz, LR
Barnes, W
Lee, S
Auerswald, CL
AF Jennings, Jacky M.
Ellen, Jonathan M.
Deeds, Bethany Griffin
Harris, D. Robert
Muenz, Larry R.
Barnes, William
Lee, Sonia
Auerswald, Colette L.
CA Adolescent Trials Network HIV AIDS
TI RECENT PARTNER-SPECIFIC HIV TRANSMISSION RISK FOR YOUTH LIVING WITH HIV
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Meeting Abstract
C1 [Jennings, Jacky M.; Ellen, Jonathan M.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Jennings, Jacky M.; Ellen, Jonathan M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA.
[Deeds, Bethany Griffin] Natl Inst Drug Abuse, Div Epidemiol, Serv & Prevent Res, Bethesda, MD USA.
[Harris, D. Robert; Muenz, Larry R.] Westat Corp, Rockville, MD USA.
[Barnes, William] George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA.
[Lee, Sonia] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA.
[Auerswald, Colette L.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
[Auerswald, Colette L.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD FEB
PY 2009
VL 44
IS 2
MA 29
BP S25
EP S26
PG 2
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 406BN
UT WOS:000263270100059
ER
PT J
AU Alexis, NE
Zhou, H
Lay, JC
Devlin, R
Kleeberger, S
Peden, DB
AF Alexis, N. E.
Zhou, H.
Lay, J. C.
Devlin, R.
Kleeberger, S.
Peden, D. B.
TI GSTM1(null) Has No Effect on the FEV1 Response to Acute Ozone Exposure
but Significantly Affects the Proportion of Inflammatory Cells in the
Airways of Allergic and Non Allergic Individuals
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Alexis, N. E.; Zhou, H.; Lay, J. C.; Peden, D. B.] Ctr Environm Med Asthma Lung Biol, Chapel Hill, NC USA.
[Alexis, N. E.] Univ N Carolina, Chapel Hill, NC USA.
[Devlin, R.] US EPA, Clin Res Branch, Chapel Hill, NC USA.
[Kleeberger, S.] NIEHS, Res Triangle Pk, NC USA.
RI Lay, John/A-6380-2012
NR 0
TC 0
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U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 530
BP S139
EP S139
DI 10.1016/j.jaci.2008.12.517
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301003
ER
PT J
AU Calatroni, A
Arbes, SJ
Gergen, PJ
Mitchell, HE
Zeldin, DC
AF Calatroni, A.
Arbes, S. J.
Gergen, P. J.
Mitchell, H. E.
Zeldin, D. C.
TI Classification of 19 Allergen-Specific IgE Antibodies Tested in NHANES
2005-2006
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Calatroni, A.; Arbes, S. J.; Mitchell, H. E.] Rho Inc, Chapel Hill, NC USA.
[Gergen, P. J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Zeldin, D. C.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
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 FEB
PY 2009
VL 123
IS 2
MA 740
BP S193
EP S193
DI 10.1016/j.jaci.2008.12.732
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301213
ER
PT J
AU Carter, MC
Uzzaman, A
Maric, I
Noel, P
Metcalfe, D
AF Carter, M. C.
Uzzaman, A.
Maric, I.
Noel, P.
Metcalfe, D.
TI Long Term Clinical and Histologic Follow-up of Pediatric Onset
Mastocytosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Carter, M. C.; Uzzaman, A.; Metcalfe, D.] NIAID, NIH, LAD, Bethesda, MD 20892 USA.
[Maric, I.; Noel, P.] NIH, CC, Bethesda, MD 20892 USA.
NR 0
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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 FEB
PY 2009
VL 123
IS 2
MA 763
BP S199
EP S199
DI 10.1016/j.jaci.2008.12.756
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301236
ER
PT J
AU Cheadle, C
Gao, PS
Grigoryev, D
Rafaels, NM
Wright, JM
Plunkett, BA
Chen, YC
Stockton, M
Togias, A
Beaty, TH
Mathias, RA
Schroeder, JT
Barnes, KC
AF Cheadle, C.
Gao, P. S.
Grigoryev, D.
Rafaels, N. M.
Wright, J. M.
Plunkett, B. A.
Chen, Y. C.
Stockton, M.
Togias, A.
Beaty, T. H.
Mathias, R. A.
Schroeder, J. T.
Barnes, K. C.
TI Identification of a Transcriptional Signature Associated with Specific
Immune Response to Cockroach Allergen
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Cheadle, C.; Gao, P. S.; Grigoryev, D.; Rafaels, N. M.; Wright, J. M.; Plunkett, B. A.; Chen, Y. C.; Stockton, M.; Togias, A.; Schroeder, J. T.; Barnes, K. C.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Beaty, T. H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mathias, R. A.] NHGRI, NIH, Baltimore, MD USA.
NR 0
TC 0
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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 FEB
PY 2009
VL 123
IS 2
MA 855
BP S222
EP S222
DI 10.1016/j.jaci.2008.12.850
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301327
ER
PT J
AU Chen, L
Huang, J
Kuo, M
Wang, J
Huang, H
Huang, S
AF Chen, L.
Huang, J.
Kuo, M.
Wang, J.
Huang, H.
Huang, S.
TI Interaction of Clara Cell 10 kd Protein (CC10) and Formyl Peptide
Receptor-Like 1 (FPRL1) Suppresses Lung Fibroblast Cytokine Release and
Neutrophil Superoxide Generation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Chen, L.; Huang, J.; Huang, H.] Chang Gung Mem Hosp, Tao Yuan, Taiwan.
[Chen, L.; Huang, J.] Chang Gung Univ, Tao Yuan, Taiwan.
[Kuo, M.] Chang Gung Univ, Inst Basic Med Sci, Dept Microbiol & Immunol, Tao Yuan, Taiwan.
[Wang, J.] Natl Canc Inst, Mol Immunoregulat Lab, Frederick, MD USA.
[Huang, S.] Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA.
NR 0
TC 1
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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 FEB
PY 2009
VL 123
IS 2
MA 174
BP S49
EP S49
DI 10.1016/j.jaci.2008.12.154
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300187
ER
PT J
AU DiVietro, JA
Bansal, G
Kuehn, HS
Gilfillan, AM
Druey, KM
AF DiVietro, J. A.
Bansal, G.
Kuehn, H. S.
Gilfillan, A. M.
Druey, K. M.
TI RGS13 Controls G-Protein-Coupled Receptor-Evoked Responses of Human Mast
Cells
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [DiVietro, J. A.; Bansal, G.; Kuehn, H. S.; Gilfillan, A. M.; Druey, K. M.] NIH, Bethesda, MD 20892 USA.
NR 0
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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 FEB
PY 2009
VL 123
IS 2
MA 753
BP S196
EP S196
DI 10.1016/j.jaci.2008.12.746
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301226
ER
PT J
AU Donohue, KM
Perera, F
Chanock, S
Tang, D
Hoepner, L
Wang, S
Liu, R
Chen, R
Miller, RL
AF Donohue, K. M.
Perera, F.
Chanock, S.
Tang, D.
Hoepner, L.
Wang, S.
Liu, R.
Chen, R.
Miller, R. L.
TI GST Polymorphisms and Atopic Dermatitis in an Inner City Cohort
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy Asthma & Immunol (AAAAI)
C1 [Donohue, K. M.] Columbia Presbyterian Med Ctr, New York, NY 10032 USA.
[Chanock, S.; Chen, R.] NCI, Bethesda, MD 20892 USA.
[Tang, D.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
[Hoepner, L.] Columbia Univ, Columbia Ctr Childrens Environm Hlth, Mailman Sch Publ Hlth, New York, NY USA.
[Hoepner, L.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
[Miller, R. L.] Columbia Univ, New York Presbyterian Hosp, New York, NY USA.
NR 0
TC 0
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U1 0
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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 FEB
PY 2009
VL 123
IS 2
SU S
MA 259
BP S71
EP S71
DI 10.1016/j.jaci.2008.12.241
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300272
ER
PT J
AU Gao, L
Coe, E
Campbell, M
Yang, M
Hand, T
Rafaels, NM
Poloczek, A
Watson, H
Dunston, G
Hansel, N
Diette, G
Adkinson, N
Mathias, RA
Beaty, TH
Johns, RA
Barnes, KC
AF Gao, L.
Coe, E.
Campbell, M.
Yang, M.
Hand, T.
Rafaels, N. M.
Poloczek, A.
Watson, H.
Dunston, G.
Hansel, N.
Diette, G.
Adkinson, N., Jr.
Mathias, R. A.
Beaty, T. H.
Johns, R. A.
Barnes, K. C.
TI Polymorphisms in Resistin (RETN) and Resistin-like Beta (RETNLB) and
Risk of Asthma in Independent Populations of African Descent
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Gao, L.; Coe, E.; Campbell, M.; Yang, M.; Hand, T.; Rafaels, N. M.; Poloczek, A.; Hansel, N.; Diette, G.; Adkinson, N., Jr.; Beaty, T. H.; Johns, R. A.; Barnes, K. C.] Johns Hopkins Univ, Baltimore, MD USA.
[Watson, H.] Univ W Indies, W Indies, Barbados.
[Dunston, G.] Howard Univ, Washington, DC 20059 USA.
[Mathias, R. A.] NHGRI, Baltimore, MD USA.
NR 0
TC 0
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 633
BP S166
EP S166
DI 10.1016/j.jaci.2008.12.623
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301106
ER
PT J
AU Gruenberg, DA
Gern, JE
Holland, SM
Seroogy, CM
AF Gruenberg, D. A.
Gern, J. E.
Holland, S. M.
Seroogy, C. M.
TI Overwhelming MAI and Pneumococcal Infection in a 19 Month Female with
Normal IFN gamma RI Expression
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Gruenberg, D. A.; Gern, J. E.; Seroogy, C. M.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA.
[Holland, S. M.] NIH, Bethesda, MD 20892 USA.
NR 0
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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 FEB
PY 2009
VL 123
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MA 35
BP S13
EP S13
DI 10.1016/j.jaci.2008.12.062
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300046
ER
PT J
AU Haberg, SE
AF Haberg, S. E.
TI Folic Acid Supplements in Pregnancy and Respiratory Health in Early
Childhood
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Haberg, S. E.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
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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 FEB
PY 2009
VL 123
IS 2
MA 55
BP S18
EP S18
DI 10.1016/j.jaci.2008.12.083
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300066
ER
PT J
AU Jaramillo, R
Massing, M
Sichere, SH
Wood, RA
Bock, SA
Burks, AW
Zeldin, DC
Liu, AH
AF Jaramillo, R.
Massing, M.
Sichere, S. H.
Wood, R. A.
Bock, S. A.
Burks, A. W.
Zeldin, D. C.
Liu, A. H.
TI High-Level Sensitization to Foods is Associated with Asthma ER Visits
and Current Asthma in the US: Results from NHANES 2005-2006
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Jaramillo, R.; Massing, M.] SRA Int Inc, Durham, NC USA.
[Sichere, S. H.] Mt Sinai Sch Med, Jaffe Food Allergy Inst, New York, NY USA.
[Wood, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Bock, S. A.; Liu, A. H.] Natl Jewish Hlth, Denver, CO USA.
[Bock, S. A.; Liu, A. H.] Univ Colorado, Sch Med, Aurora, CO USA.
[Burks, A. W.] Duke Univ, Med Ctr, Durham, NC USA.
[Zeldin, D. C.] NIH Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 419
BP S111
EP S111
DI 10.1016/j.jaci.2008.12.404
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300432
ER
PT J
AU Josephs, AR
Prussin, C
AF Josephs, A. R.
Prussin, C.
TI Assessment of Spleen Tyrosine Kinase Expression in Basophils using Flow
Cytometry
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Josephs, A. R.; Prussin, C.] NIAID, NIH, Bethesda, MD 20892 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 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 756
BP S197
EP S197
DI 10.1016/j.jaci.2008.12.749
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301229
ER
PT J
AU Kirshenbaum, AS
Wu, Y
Brown, JM
Gilfillan, AM
Lantz, LM
Reese, G
Vieths, S
Metcalfe, DD
AF Kirshenbaum, A. S.
Wu, Y.
Brown, J. M.
Gilfillan, A. M.
Lantz, L. M.
Reese, G.
Vieths, S.
Metcalfe, D. D.
TI Identification of Shrimp Tropomyosin (Pen a 1) as an IgE-Independent
Mast Cell Secretagogue
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kirshenbaum, A. S.; Wu, Y.; Brown, J. M.; Gilfillan, A. M.; Lantz, L. M.; Metcalfe, D. D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Reese, G.; Vieths, S.] Paul Ehrlich Inst, D-6070 Langen, Germany.
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 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 664
BP S174
EP S174
DI 10.1016/j.jaci.2008.12.655
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301137
ER
PT J
AU Klion, AD
Wilson, TM
Brown, M
Maric, I
Metcalfe, DD
Nutman, TB
AF Klion, A. D.
Wilson, T. M.
Brown, M.
Maric, I.
Metcalfe, D. D.
Nutman, T. B.
TI Surface and Soluble IL-5 Receptor Alpha Expression in Patients with
Eosinophilia and Mastocytosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Klion, A. D.; Wilson, T. M.; Brown, M.; Maric, I.; Metcalfe, D. D.; Nutman, T. B.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 973
BP S251
EP S251
DI 10.1016/j.jaci.2008.12.970
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301445
ER
PT J
AU Liu, AH
Sicherer, SH
Wood, RA
Bock, SA
Burks, AW
Jaramillo, R
Spruell, B
Massing, M
Zeldin, DC
AF Liu, A. H.
Sicherer, S. H.
Wood, R. A.
Bock, S. A.
Burks, A. W.
Jaramillo, R.
Spruell, B.
Massing, M.
Zeldin, D. C.
TI In the United States, Black Male Children have an Increased Risk of Food
Allergy: Results from NHANES 2005-2006
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Liu, A. H.; Bock, S. A.] Natl Jewish Hlth, Denver, CO USA.
[Liu, A. H.; Bock, S. A.] Univ Colorado, Sch Med, Aurora, CO USA.
[Sicherer, S. H.] Mt Sinai Sch Med, Jaffe Food Allergy Inst, New York, NY USA.
[Wood, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Burks, A. W.] Duke Univ, Med Ctr, Durham, NC USA.
[Jaramillo, R.; Spruell, B.; Massing, M.] SRA Int Inc, Durham, NC USA.
[Zeldin, D. C.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
NR 0
TC 4
Z9 4
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 1037
BP S267
EP S267
DI 10.1016/j.jaci.2008.12.1036
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301509
ER
PT J
AU Pomes, A
Li, M
Glesner, J
Wunschmann, S
King, EM
Chapman, MD
Wlodawer, A
Gustchina, A
AF Pomes, A.
Li, M.
Glesner, J.
Wuenschmann, S.
King, E. M.
Chapman, M. D.
Wlodawer, A.
Gustchina, A.
TI The X-Ray Crystal Structure of Two Complexes of the Cockroach Allergen
Bla g 2 with Fragments of Monoclonal Antibodies Defines Two
Non-overlapping Epitopes
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Pomes, A.; Glesner, J.; Wuenschmann, S.; King, E. M.; Chapman, M. D.] INDOOR Biotechnol Inc, Charlottesville, VA USA.
[Li, M.] SAIC Frederick, Basic Res Program, Frederick, MD USA.
[Li, M.; Wlodawer, A.; Gustchina, A.] Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 885
BP S229
EP S229
DI 10.1016/j.jaci.2008.12.881
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301357
ER
PT J
AU Radinger, MK
Kim, M
Metcalfe, DD
Gilfillan, AM
AF Radinger, M. K.
Kim, M.
Metcalfe, D. D.
Gilfillan, A. M.
TI Lentivirus-mediated Short Hairpin RNA Knockdown Of Glycogen Synthase
Kinase-3 beta Markedly Decreases Fc epsilon RI-mediated Human Mast Cell
Cytokine Production
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Radinger, M. K.; Kim, M.; Metcalfe, D. D.; Gilfillan, A. M.] NIAID, Lab Allerg Dis, Natl Inst Hlth, Bethesda, MD 20892 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 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 758
BP S197
EP S197
DI 10.1016/j.jaci.2008.12.751
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301231
ER
PT J
AU Sever, ML
Arbes, SJ
Watson, EC
Spencer, HL
Vaughn, B
Vann, WF
Zeldin, DC
AF Sever, M. L.
Arbes, S. J., Jr.
Watson, E. C.
Spencer, H. L., Jr.
Vaughn, B.
Vann, W. F., Jr.
Zeldin, D. C.
TI Oral Bacteria and History of Allergic Disease in Children: A Pilot Study
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Sever, M. L.; Watson, E. C.; Spencer, H. L., Jr.; Zeldin, D. C.] NIEHS, Environm Cardiopulm Dis Grp, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Sever, M. L.] Univ N Carolina, UNC Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Arbes, S. J., Jr.; Vaughn, B.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Spencer, H. L., Jr.] Meharry Med Coll, Sch Dent, Nashville, TN 37208 USA.
[Vann, W. F., Jr.] Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC 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 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 59
BP S19
EP S19
DI 10.1016/j.jaci.2008.12.087
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300070
ER
PT J
AU Slager, RE
Levan, TD
Poole, JA
Sandler, DP
Hoppin, JA
AF Slager, R. E.
LeVan, T. D.
Poole, J. A.
Sandler, D. P.
Hoppin, J. A.
TI Occupational Risk Factors for Rhinitis Among Farmers in the Agricultural
Health Study
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Slager, R. E.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[LeVan, T. D.; Poole, J. A.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Sandler, D. P.; Hoppin, J. A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 1031
BP S266
EP S266
DI 10.1016/j.jaci.2008.12.1029
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301503
ER
PT J
AU Tran, D
AF Tran, D.
TI Dysfunctional FOXP3+Regulatory T cells in leukocyte Adhesion Deficiency
Type 1 (LAD-1) Patients with Reversion Mutations and Inflammatory Bowel
Disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Tran, D.] NIAID, NIH, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 43
BP S15
EP S15
DI 10.1016/j.jaci.2008.12.070
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300054
ER
PT J
AU Tsai, YJ
Mathias, R
Grant, A
Rafaels, N
Hand, T
Togias, A
Hansel, N
Diette, G
Adkinson, NF
Liu, MC
Faruque, M
Watson, H
Scott, A
Ruczinski, I
Dunston, G
Beaty, T
Barnes, KC
AF Tsai, Y. J.
Mathias, R.
Grant, A.
Rafaels, N.
Hand, T.
Togias, A.
Hansel, N.
Diette, G.
Adkinson, N. F., Jr.
Liu, M. C.
Faruque, M.
Watson, H.
Scott, A.
Ruczinski, I.
Dunston, G.
Beaty, T.
Barnes, K. C.
TI A Genome Wide Approach to Identify Genetic Determinants of Asthma Traits
Related to Airway Function in Two Populations of African Descent
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Mathias, R.] NHGRI, Baltimore, MD USA.
[Togias, A.] NIAID, Bethesda, MD 20892 USA.
[Faruque, M.; Dunston, G.] Howard Univ, Washington, DC 20059 USA.
NR 0
TC 0
Z9 1
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 567
BP S148
EP S148
DI 10.1016/j.jaci.2008.12.555
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596301040
ER
PT J
AU Visness, CM
Daniels, JL
Kaufman, JS
Yeatts, KB
London, SJ
Siega-Riz, AM
Calatroni, A
Zeldin, DC
AF Visness, C. M.
Daniels, J. L.
Kaufman, J. S.
Yeatts, K. B.
London, S. J.
Siega-Riz, A. M.
Calatroni, A.
Zeldin, D. C.
TI Childhood Obesity is Associated with Both Atopy and Current Asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Visness, C. M.; Calatroni, A.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Daniels, J. L.; Kaufman, J. S.; Yeatts, K. B.; Siega-Riz, A. M.] Univ N Carolina, Chapel Hill, NC USA.
[London, S. J.; Zeldin, D. C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
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 FEB
PY 2009
VL 123
IS 2
MA 264
BP S72
EP S72
DI 10.1016/j.jaci.2008.12.246
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300277
ER
PT J
AU Wu, H
Romieu, I
Sienra-Monge, J
Li, H
del Rio-Navarro, B
London, SJ
AF Wu, H.
Romieu, I.
Sienra-Monge, J.
Li, H.
del Rio-Navarro, B.
London, S. J.
TI Genetic Variation In ORM1-like 3 (ORMDL3) And Gasdermin-like (GSDML) And
Childhood Asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Wu, H.; Li, H.; London, S. J.] NIEHS, NIH, Lab Resp Biol, Div Intramural Res,DHHS, Res Triangle Pk, NC 27709 USA.
[Romieu, I.] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
[Sienra-Monge, J.; del Rio-Navarro, B.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 185
BP S52
EP S52
DI 10.1016/j.jaci.2008.12.165
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300198
ER
PT J
AU Yang, Z
Mukhopadhyay, I
Druey, KM
AF Yang, Z.
Mukhopadhyay, I.
Druey, K. M.
TI Regulation of Airway Smooth Muscle Functions by RGS5
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the
American-Academy-of-Allergy-Asthma-and-Immunology
CY MAR 13-17, 2009
CL Washington, DC
SP Amer Acad Allergy, Asthma & Immunol
C1 [Yang, Z.; Mukhopadhyay, I.; Druey, K. M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2009
VL 123
IS 2
MA 449
BP S118
EP S118
DI 10.1016/j.jaci.2008.12.435
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 410RR
UT WOS:000263596300462
ER
PT J
AU Stergiopoulou, T
Meletiadis, J
Sein, T
Papaioannidou, P
Tsiouris, I
Roilides, E
Walsh, TJ
AF Stergiopoulou, Theodouli
Meletiadis, Joseph
Sein, Tin
Papaioannidou, Paraskevi
Tsiouris, Ioannis
Roilides, Emmanuel
Walsh, Thomas J.
TI Comparative pharmacodynamic interaction analysis between ciprofloxacin,
moxifloxacin and levofloxacin and antifungal agents against Candida
albicans and Aspergillus fumigatus
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
ID HEALTHY-VOLUNTEERS; J774 MACROPHAGES; PATHOGENIC FUNGI; AMPHOTERICIN-B;
4 QUINOLONES; IN-VITRO; FLUCONAZOLE; COMBINATION; EFFLUX; PLASMA
AB Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Ciprofloxacin, a carboxyfluoroquinolone, was previously observed to demonstrate the pharmacodynamic interactions with antifungal agents by altering their growth inhibitory activity against Candida albicans and Aspergillus fumigatus. However, little is known about the interaction between other extended-spectrum fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents against C. albicans and A. fumigatus.
Using a microdilution chequerboard technique, we employed isobolographic analysis adapted to incorporate a non-active agent in order to analyse the potential in vitro interaction between ciprofloxacin, levofloxacin or moxifloxacin and the following representative antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin.
Synergistic interactions [interaction indices (Iis) 0.69-0.83, P < 0.05] were observed between amphotericin B (0.07-0.31 mg/L) and either ciprofloxacin (0.19-7.65 mg/L) or levofloxacin (0.41-32.88 mg/L) against C. albicans and A. fumigatus. Synergy (Iis 0.56-0.87, P < 0.05) also was found between voriconazole (0.09-0.14 mg/L) and ciprofloxacin (0.22-11.41 mg/L) as well as between caspofungin (8.94-22.07 mg/L) and levofloxacin (0.14-5.17 mg/L) against A. fumigatus. Some antagonistic (Iis 1.16-1.29, P < 0.05) interactions were observed between fluoroquinolones and fluconazole against C. albicans. In general, ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin and levofloxacin against both C. albicans and A. fumigatus.
The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections.
C1 [Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Roilides, Emmanuel; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Paediat Oncol Branch, Bethesda, MD 20892 USA.
[Stergiopoulou, Theodouli; Tsiouris, Ioannis; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokrat Hosp, Pediat Dept 3, GR-54006 Thessaloniki, Greece.
[Meletiadis, Joseph] Univ Athens, Attiko Univ Hosp, Lab Clin Microbiol, Athens, Greece.
[Sein, Tin] SAIC Frederick Inc, Frederick, MD 21702 USA.
[Papaioannidou, Paraskevi] Aristotle Univ Thessaloniki, Fac Med, Dept Pharmacol, GR-54006 Thessaloniki, Greece.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Paediat Oncol Branch, 10 Ctr Dr,Bldg 10-Rm 1-5750, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
RI Papaioannidou, Paraskevi/D-9864-2011;
OI Papaioannidou, Paraskevi/0000-0001-8880-0288
FU National Cancer Institute, Bethesda, MD, USA; Hippokration Hospital,
Aristotle University of Thessaloniki, Greece
FX This study was supported by the intramural research programme of the
National Cancer Institute, Bethesda, MD, USA, and by the Hippokration
Hospital, Aristotle University of Thessaloniki, Greece.
NR 19
TC 21
Z9 23
U1 0
U2 3
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 FEB
PY 2009
VL 63
IS 2
BP 343
EP 348
DI 10.1093/jac/dkn473
PG 6
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 395LD
UT WOS:000262524700021
PM 19109335
ER
PT J
AU Hortobagyi, T
Richardson, SP
Lomarev, M
Shamim, E
Meunier, S
Russman, H
Dang, N
Hallett, M
AF Hortobagyi, Tibor
Richardson, Sarah Pirio
Lomarev, Mikhael
Shamim, Ejaz
Meunier, Sabine
Russman, Heike
Dang, Nguyet
Hallett, Mark
TI Chronic low-frequency rTMS of primary motor cortex diminishes exercise
training-induced gains in maximal voluntary force in humans
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE muscle; transcranial magnetic stimulation; cortical excitability
ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN CORTICOSPINAL EXCITABILITY;
EVOKED V-WAVE; H-REFLEX; ELECTRICAL-STIMULATION; NEURAL ADAPTATIONS;
NEUROMUSCULAR FATIGUE; CORTICAL PLASTICITY; MUSCLE ACTIVATION;
SKELETAL-MUSCLE
AB Hortobagyi T, Richardson SP, Lomarev M, Shamim E, Meunier S, Russman H, Dang N, Hallett M. Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans. J Appl Physiol 106: 403-411, 2009. First published November 13, 2008; doi: 10.1152/japplphysiol. 90701.2008.-Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation ( rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) ( 5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS ( Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.
C1 [Hortobagyi, Tibor] E Carolina Univ, Dept Exercise & Sport Sci, Greenville, NC 27858 USA.
[Richardson, Sarah Pirio] Univ New Mexico, Albuquerque, NM 87131 USA.
[Lomarev, Mikhael] Bekhierev Neuropsychol Inst, St Petersburg, Russia.
[Shamim, Ejaz; Meunier, Sabine; Dang, Nguyet; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA.
[Russman, Heike] CHU Vaudois, CH-1011 Lausanne, Switzerland.
RP Hortobagyi, T (reprint author), E Carolina Univ, Dept Exercise & Sport Sci, 332A Ward Sports Med Bldg, Greenville, NC 27858 USA.
EM hortobagyit@ecu.edu
RI meunier, sabine/G-7622-2014
OI meunier, sabine/0000-0002-6167-4602
FU National Institute of Neurological Disorders and Stroke [NS-049783];
East Carolina University's Division of Research and Graduate Studies
FX This work was supported in part by National Institute of Neurological
Disorders and Stroke Grant NS-049783 and by a Research Development Grant
from East Carolina University's Division of Research and Graduate
Studies.
NR 59
TC 17
Z9 18
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD FEB
PY 2009
VL 106
IS 2
BP 403
EP 411
DI 10.1152/japplphysiol.90701.2008
PG 9
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 403ZL
UT WOS:000263120400010
PM 19008488
ER
PT J
AU Scaglione, BJ
Salerno, E
Gala, K
Pan, M
Langer, JA
Mostowski, HS
Bauer, S
Marti, G
Li, Y
Tsiagbe, VK
Raveche, ES
AF Scaglione, Brian J.
Salerno, Erica
Gala, Kinisha
Pan, Manjing
Langer, Jerome A.
Mostowski, Howard S.
Bauer, Steven
Marti, Gerald
Li, Yu
Tsiagbe, Vincent K.
Raveche, Elizabeth S.
TI Regulatory T cells as central regulators of both autoimmunity and B cell
malignancy in New Zealand Black mice
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Autoimmunity; Regulatory T cells; Tumor immunity
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
IMMUNOLOGICAL SELF-TOLERANCE; AUTO-IMMUNE DISEASE; NZB MICE;
INTERFERON-ALPHA; MURINE LUPUS; LYMPHOPROLIFERATIVE DISEASE;
AUTOANTIBODY PRODUCTION; LEUKOCYTE INTERFERONS
AB Regulatory T cells (Tregs) play an important role in protection against autoimmune disease and are also known to be potent inhibitors of anti-tumor immune responses. The New Zealand Black (NZB) mouse is a murine model for both autoimmune diseases, since high levels of autoantibodies are present, and human CLL, due to the expansion of malignant B-1 cells. In this study, we examined the functional role of CD4(+)CD25(+) Foxp3(+) Tregs in these different manifestations. Flow cytometric analysis showed increased levels of Tregs in NZB mice compared to healthy C57Bl/6 controls. Aged NZB mice that have developed a B-1 cell malignancy identified as IgM(+)CD5(+), have the most pronounced increase in Tregs. Ex vivo treatment of splenocytes from NZB mice with IFN-alpha resulted in a decrease in the frequency of Tregs and malignant B-1 cells. In vivo treatment of both NZB and C57Bl/6 mice with poly (I:C), a potent inducer of IFN-alpha, also led to a decrease in the levels of Tregs and malignant B-1 cells (NZB only) while amplifying autoimmune manifestations. These results indicate that while high levels of Tregs found in NZB mice might suppress a more severe autoimmune disease, they may also contribute to the development of the B cell malignancy. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Salerno, Erica; Gala, Kinisha; Tsiagbe, Vincent K.; Raveche, Elizabeth S.] Univ Med & Dent, New Jersey Med Sch, Newark, NJ 07103 USA.
[Pan, Manjing; Langer, Jerome A.] Univ Med & Dent, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Mostowski, Howard S.; Bauer, Steven; Marti, Gerald] US FDA, Ctr Biol Evaluat, NIH, Bethesda, MD 20892 USA.
[Tsiagbe, Vincent K.] Univ Med & Dent, New Jersey Dent Sch, Newark, NJ 07103 USA.
RP Raveche, ES (reprint author), Univ Med & Dent, New Jersey Med Sch, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA.
EM raveches@umdnj.edu
OI Bauer, Steven/0000-0003-2831-846X; Langer, Jerome/0000-0002-4617-3260
NR 68
TC 8
Z9 8
U1 0
U2 2
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD FEB
PY 2009
VL 32
IS 1
BP 14
EP 23
DI 10.1016/j.jaut.2008.10.001
PG 10
WC Immunology
SC Immunology
GA 413BT
UT WOS:000263768600003
PM 19022624
ER
PT J
AU Wang, J
Zhou, XB
Li, FH
Bradley, PL
Chang, SF
Perrimon, N
Wong, STC
AF Wang, Jun
Zhou, Xiaobo
Li, Fuhai
Bradley, Pamela L.
Chang, Shih-Fu
Perrimon, Norbert
Wong, Stephen T. C.
TI An image score inference system for RNAi genome-wide screening based on
fuzzy mixture regression modeling
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE High-content screening; Image score inference
ID SEGMENTATION; TEXTURE; RHO; CLASSIFICATION; RECOGNITION; FEATURES; CELLS
AB With recent advances in fluorescence microscopy imaging techniques and methods of gene knock down by RNA interference (RNAi), genome-scale high-content screening (HCS) has emerged as a powerful approach to systematically identify all parts of complex biological processes. However, a critical barrier preventing fulfillment of the success is the lack of efficient and robust methods for automating RNAi image analysis and quantitative evaluation of the gene knock down effects on huge volume of HCS data. Facing such opportunities and challenges, we have started investigation of automatic methods towards the development of a fully automatic RNAi-HCS system. Particularly important are reliable approaches to cellular phenotype classification and image-based gene function estimation.
We have developed a HCS analysis platform that consists of two main components: fluorescence image analysis and image scoring. For image analysis, we used a two-step enhanced watershed method to extract cellular boundaries from HCS images. Segmented cells were classified into several predefined phenotypes based on morphological and appearance features. Using statistical characteristics of the identified phenotypes as a quantitative description of the image, a score is generated that reflects gene function. Our scoring model integrates fuzzy gene class estimation and single regression models. The final functional score of an image was derived using the weighted combination of the inference from several support vector-based regression models. We validated our phenotype classification method and scoring system on our cellular phenotype and gene database with expert ground truth labeling.
We built a database of high-content, 3-channel, fluorescence microscopy images of Drosophila Kc(167) cultured cells that were treated with RNAi to perturb gene function. The proposed informatics system for microscopy image analysis is tested on this database. Both of the two main components, automated phenotype classification and image scoring system, were evaluated. The robustness and efficiency of our system were validated in quantitatively predicting the biological relevance of genes. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Wang, Jun; Chang, Shih-Fu] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA.
[Zhou, Xiaobo; Li, Fuhai; Wong, Stephen T. C.] Harvard Univ, Sch Med, Ctr Bioinformat, Harvard Ctr Neurodegenerat & Repair, Boston, MA 02215 USA.
[Bradley, Pamela L.] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Wang, J (reprint author), Columbia Univ, Dept Elect Engn, 1300 SW Mudd,500 W 120th St, New York, NY 10027 USA.
EM jwang@columbia.edu; zhou@crystal.harvard.edu
FU HCNR; Harvard Medical School (Wong)
FX The authors thank Baillie Yip for labeling training data sets. They also
thank research members of the Life Science Imaging Group of the Center
for Bioinformatics, Harvard Center for Neurodegeneration and Repair
(HCNR) and Brigham and Women's Hospital, Harvard Medical School, for
their technical comments. The research is funded by the HCNR, Harvard
Medical School (Wong).
NR 35
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 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD FEB
PY 2009
VL 42
IS 1
BP 32
EP 40
DI 10.1016/j.jbi.2008.04.007
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 414RK
UT WOS:000263882700004
PM 18547870
ER
PT J
AU Vaidyanathan, J
Vaidlyanathan, TK
Ravichandran, S
AF Vaidyanathan, J.
Vaidlyanathan, T. K.
Ravichandran, S.
TI Computer Simulated Screening of Dentin Bonding Primer Monomers Through
Analysis of Their Chemical Functions and Their Spatial 3D Alignment
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
LA English
DT Article
DE adhesion; collagen; computer modeling/simulation; dental/craniofacial
material; tissue adhesion
ID COLLAGEN; BINDING
AB Binding interactions between dentin bonding primer monomers and dentinal collagen were studied by an analysis of their chemical functions and their spatial 3D alignment. A trial set of 12 monomers used as primers in dentin adhesives was characterized to assess them for binding to a complementary target. HipHop utility in the Catalyst software from Accelrys was used for the study. Ten hypotheses were generated by HipHop procedures involving (a) conformational generation using a poling technique to promote conformational variation, (b) extraction of functions to remodel ligands as function-based structures, and (c) identification of common patterns of functional alignment displayed by low energy conformations. The hypotheses, designated as pharmacaphores, were also scored and ranked. Analysis of pharmacaphore models through mapping of ligands revealed important differences between ligands. Top-ranked poses from direct docking simulations using type 1 collagen target were mapped in a rigid manner to the highest ranked pharmacophore model. The visual match observed in mapping and associated fit values suggest a strong correspondence between direct and indirect docking simulations. The results elegantly demonstrate that an indirect approach used to identify pharmacaphore models from adhesive ligands without a target may be a simple and viable approach to assess their intermolecular interactions with an intended target. Inexpensive indirect/direct virtual screening of hydrophilic monomer candidates may be a practical way to assess their initial promise for dentin primer use well before additional experimental evaluation of their priming/bonding efficacy. This is also of value in the search/design of new compounds for priming dentin. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 88B: 447-457, 2009
C1 [Vaidyanathan, J.; Vaidlyanathan, T. K.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Restorat Dent, Newark, NJ 07103 USA.
[Ravichandran, S.] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Vaidyanathan, J (reprint author), Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Restorat Dent, Newark, NJ 07103 USA.
EM jvaidyan@umdnj.edu
FU NIDCR NIH HHS [R01 DE 14370]
NR 20
TC 3
Z9 3
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4973
J9 J BIOMED MATER RES B
JI J. Biomed. Mater. Res. Part B
PD FEB
PY 2009
VL 88B
IS 2
BP 447
EP 457
DI 10.1002/jbm.b.31134
PG 11
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 397TB
UT WOS:000262683900018
PM 18546179
ER
PT J
AU Shen, Y
Vernon, R
Baker, D
Bax, A
AF Shen, Yang
Vernon, Robert
Baker, David
Bax, Ad
TI De novo protein structure generation from incomplete chemical shift
assignments
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE NMR chemical shift; Protein structure prediction; Solid-state NMR
structure determination; Paramagnetic protein; CS-Rosetta
ID STATE NMR-SPECTROSCOPY; MOLECULAR FRAGMENT REPLACEMENT; SOLID-STATE;
SEQUENCE HOMOLOGY; MICROCRYSTALLINE UBIQUITIN; SECONDARY STRUCTURE;
NUCLEIC-ACIDS; C-13 NMR; CONFORMATION; RESOLUTION
AB NMR chemical shifts provide important local structural information for proteins. Consistent structure generation from NMR chemical shift data has recently become feasible for proteins with sizes of up to 130 residues, and such structures are of a quality comparable to those obtained with the standard NMR protocol. This study investigates the influence of the completeness of chemical shift assignments on structures generated from chemical shifts. The Chemical-Shift-Rosetta (CS-Rosetta) protocol was used for de novo protein structure generation with various degrees of completeness of the chemical shift assignment, simulated by omission of entries in the experimental chemical shift data previously used for the initial demonstration of the CS-Rosetta approach. In addition, a new CS-Rosetta protocol is described that improves robustness of the method for proteins with missing or erroneous NMR chemical shift input data. This strategy, which uses traditional Rosetta for pre-filtering of the fragment selection process, is demonstrated for two paramagnetic proteins and also for two proteins with solid-state NMR chemical shift assignments.
C1 [Shen, Yang; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Vernon, Robert; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Vernon, Robert; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Shen, Yang/C-3064-2008; Baker, David/K-8941-2012
OI Shen, Yang/0000-0003-1408-8034; Baker, David/0000-0001-7896-6217
FU NIDDK; NIH
FX This work was funded by the Intramural Research Program of the NIDDK,
NIH, and by the Intramural AIDS-Targeted Antiviral Program of the Office
of the Director, NIH; the NIGMS, NIH, and the Howard Hughes Medical
Institutes ( to D. B.). We also thank Rosetta@home participants and the
BOINC project for contributing computing power.
NR 56
TC 135
Z9 137
U1 3
U2 34
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD FEB
PY 2009
VL 43
IS 2
BP 63
EP 78
DI 10.1007/s10858-008-9288-5
PG 16
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 391NT
UT WOS:000262240700001
PM 19034676
ER
PT J
AU Katz, SI
AF Katz, Stephen I.
TI Musculoskeletal Research at the National Institute of Arthritis and
Musculoskeletal and Skin Diseases: A Snapshot
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Editorial Material
C1 NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NIAMSD, NIH, Bldg 31,Room 4C32,31 Ctr Dr, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 2
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD FEB
PY 2009
VL 91A
IS 2
BP 474
EP 475
DI 10.2106/JBJS.H.01607
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 403LA
UT WOS:000263082900027
PM 19181994
ER
PT J
AU Voss, TC
Schiltz, RL
Sung, MH
Johnson, TA
John, S
Hager, GL
AF Voss, Ty C.
Schiltz, R. Louis
Sung, Myong-Hee
Johnson, Thomas A.
John, Sam
Hager, Gordon L.
TI Combinatorial probabilistic chromatin interactions produce
transcriptional heterogeneity
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Chromatin; Steroid receptor; Stochastics; Transcription
ID STOCHASTIC GENE-EXPRESSION; MAMMARY-TUMOR VIRUS; HORMONE-BINDING
DOMAINS; GLUCOCORTICOID-RECEPTOR; LIVING CELLS; SINGLE-CELL; NUCLEAR
RECEPTORS; MMTV PROMOTER; DYNAMICS; COACTIVATOR
AB Gene regulation often appears deterministic in the average cell population, but transcription is a probabilistic process at the single-cell level. Although many mechanisms are invoked to account for this behavior, it is difficult to determine how cell-to-cell variation in the interactions of transcription factors with target chromatin impact transcriptional output. Here, we use cells that contain a 200-copy tandem array of promoter or reporter gene units to simultaneously visualize transient interaction, equilibrium or steady-state binding of fluorescent-protein-labeled glucocorticoid receptor with its DNA response elements, the recruitment of diverse coregulators, and transcriptional output at the single-cell level. These regulatory proteins associate with target chromatin via a probabilistic mechanism that produces cell-to-cell variability in binding. The multiple steps of this process are partially independent and differ between individual regulators. The association level of each regulator influences the transcriptional output in individual cells, but this does not account for all transcriptional heterogeneity. Additionally, specific combinatorial interactions of the glucocorticoid receptor and coregulators with response elements regulate transcription at the single-cell level. Like many endogenous genes, the average array transcriptional activity evolves over time. This apparently deterministic average temporal promoter progression involves changes in the probability that specific combinatorial glucocorticoid receptor and coregulator interactions will occur on the response elements in single cells. These data support the emerging 'return-to-template' transcription model, which mechanistically unifies the observed extremely transient interactions between the transcription factor and response elements, cell-to-cell variability in steady-state association of factors with chromatin, and the resulting heterogeneous gene expression between individual cells.
C1 [Voss, Ty C.; Schiltz, R. Louis; Sung, Myong-Hee; Johnson, Thomas A.; John, Sam; Hager, Gordon L.] NCI, Ctr Canc Res, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Ctr Canc Res, NIH, Lab Receptor Biol & Gene Express, Bldg 41,B602, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research
FX The authors thank Richard N. Day, Catherine L. Smith, and Tom Misteli
for helpful discussion during preparation of the manuscript. The mCherry
FP cDNA was a generous gift from Roger Tsien. Anindya Hendarwanto
provided expert technical support. Tatiana Karpova assisted with
experiments performed in the NCI Core Fluorescence Imaging Facility.
This research was supported ( in part) by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. Deposited in PMC for release after 12 months.
NR 46
TC 18
Z9 18
U1 0
U2 0
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD FEB 1
PY 2009
VL 122
IS 3
BP 345
EP 356
DI 10.1242/jcs.035865
PG 12
WC Cell Biology
SC Cell Biology
GA 396HE
UT WOS:000262582000006
PM 19126674
ER
PT J
AU Carlson, GA
Findling, RL
Post, RM
Birmaher, B
Blumberg, HP
Correll, C
DelBello, MP
Fristad, M
Frazier, J
Hammen, C
Hinshaw, SP
Kowatch, R
Leibenluft, E
Meyer, SE
Pavuluri, MN
Wagner, KD
Tohen, M
AF Carlson, Gabrielle A.
Findling, Robert L.
Post, Robert M.
Birmaher, Boris
Blumberg, Hilary P.
Correll, Christoph
DelBello, Melissa P.
Fristad, Mary
Frazier, Jean
Hammen, Constance
Hinshaw, Stephen P.
Kowatch, Robert
Leibenluft, Ellen
Meyer, Stephanie E.
Pavuluri, Mani N.
Wagner, Karen Dineen
Tohen, Mauricio
TI AACAP 2006 Research Forum-Advancing Research in Early-Onset Bipolar
Disorder: Barriers and Suggestions
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID SEVERE MOOD DYSREGULATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
MAGNETIC-RESONANCE SPECTROSCOPY; FOLLOW-UP; MAJOR DEPRESSION;
RISK-FACTORS; CHILDREN; CHILDHOOD; MANIA; ADOLESCENTS
AB Objective: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity.
Method: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy.
Results: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind.
Conclusions: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace.
C1 [Findling, Robert L.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Dept Psychiat, Cleveland, OH 44106 USA.
[Carlson, Gabrielle A.] SUNY Stony Brook, Sch Med, Dept Child & Adolescent Psychiat, Stony Brook, NY 11794 USA.
[Post, Robert M.] George Washington Univ, Dept Psychiat, Bethesda, MD USA.
[Birmaher, Boris] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA.
[Blumberg, Hilary P.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Blumberg, Hilary P.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Correll, Christoph] Zucker Hillside Hosp, Glen Oaks, NY USA.
[DelBello, Melissa P.] Univ Cincinnati, Coll Med, Div Bipolar Disorders Res, Cincinnati, OH USA.
[Fristad, Mary] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Frazier, Jean] UMASS Med Sch, Dept Psychiat, Worcester, MA USA.
[Hammen, Constance] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Hinshaw, Stephen P.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
[Kowatch, Robert] Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati, OH 45267 USA.
[Leibenluft, Ellen] NIMH, Unit Affect Disorders, Pediat & Dev Neuropsychiat Branch, Mood & Anxiety Program, Bethesda, MD 20892 USA.
[Meyer, Stephanie E.] Cedars Sinai Med Ctr, Div Child & Adolescent Psychiat, Los Angeles, CA USA.
[Pavuluri, Mani N.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Wagner, Karen Dineen] Univ Texas Galveston, Med Branch, Dept Child & Adolescent Psychiat, Galveston, TX 77550 USA.
[Tohen, Mauricio] Eli Lilly & Co, Indianapolis, IN 46285 USA.
RP Findling, RL (reprint author), Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Dept Psychiat, 10524 Euclid Ave, Cleveland, OH 44106 USA.
EM robert.findling@UHhospitals.org
NR 87
TC 13
Z9 13
U1 2
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB
PY 2009
VL 19
IS 1
BP 3
EP 12
DI 10.1089/cap.2008.100
PG 10
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 415DC
UT WOS:000263913500002
PM 19232018
ER
PT J
AU Mueller, SC
Mandell, D
Leschek, EW
Pine, DS
Merke, DP
Ernst, M
AF Mueller, Sven C.
Mandell, Darcy
Leschek, Ellen W.
Pine, Daniel S.
Merke, Deborah P.
Ernst, Monique
TI Early Hyperandrogenism Affects the Development of Hippocampal Function:
Preliminary Evidence from a Functional Magnetic Resonance Imaging Study
of Boys with Familial Male Precocious Puberty
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID CONGENITAL ADRENAL-HYPERPLASIA; FACIAL EXPRESSIONS; STEROID-HORMONES;
AMYGDALA VOLUME; RAT-BRAIN; RECEPTOR; DISORDER; ANDROGEN; EMOTION;
MEMORY
AB The way in which sex hormones influence cognitive and affective brain development is poorly understood. Despite increasing knowledge in the area of pediatric mood disorders, little is known about the influence of sex hormones on the regulation of emotion. Animal studies and preliminary human studies suggest a strong impact of testosterone on limbic structures such as the hippocampus and amygdala. We used functional magnetic resonance imaging (fMRI) to examine emotional processing in familial male- precocious puberty (FMPP), an extremely rare gonadotropin-independent form of precocious puberty characterized by early excess testosterone secretion. We compared this group (n = 7, mean age = 13 +/- 3.3 years) to healthy age and sex-matched controls (n = 14, mean age = 13 +/- 2.3 years). Participants were presented with emotional and neutral face stimuli and were required either to judge the hostility of the presented face, their subjective level of anxiety, or the width of the nose of the presented faces (nonemotional condition). In a fourth, passive viewing condition, no responses were required. Boys with FMPP responded faster to fearful faces during perception of threat compared to unaffected controls. Concurrently, fMRI data revealed significant differences in hippocampus activation in response to fearful faces relative to baseline whereas controls showed no differences. In contrast, no significant activation of the amygdala was found. These data are consistent with previous studies of the effects of sex hormones on brain function and support the role of testosterone on emotional development.
C1 [Mueller, Sven C.; Mandell, Darcy; Pine, Daniel S.; Ernst, Monique] NIMH, Emot Dev & Affect Neurosci Branch, NIH, Bethesda, MD 20892 USA.
[Leschek, Ellen W.] NIDDK, NIH, Bethesda, MD USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Clin, NIH, Bethesda, MD USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA.
RP Ernst, M (reprint author), 15K North Dr, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
FU Intramural Program of the National Institute of Mental Health; Eunice
Rennedy Shriver National Institute of Child Health and Human Development
FX The research was supported by the Intramural Program of the National
Institute of Mental Health and Eunice Rennedy Shriver National Institute
of Child Health and Human Development.
NR 56
TC 15
Z9 15
U1 2
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB
PY 2009
VL 19
IS 1
BP 41
EP 50
DI 10.1089/cap.2008.031
PG 10
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 415DC
UT WOS:000263913500006
PM 19232022
ER
PT J
AU Eastell, R
Arnold, A
Brandi, ML
Brown, EM
D'Amour, P
Hanley, DA
Rao, DS
Rubin, MR
Goltzman, D
Silverberg, SJ
Marx, SJ
Peacock, M
Mosekilde, L
Bouillon, R
Lewiecki, EM
AF Eastell, R.
Arnold, A.
Brandi, M. L.
Brown, E. M.
D'Amour, P.
Hanley, D. A.
Rao, D. Sudhaker
Rubin, M. R.
Goltzman, D.
Silverberg, S. J.
Marx, S. J.
Peacock, M.
Mosekilde, L.
Bouillon, R.
Lewiecki, E. M.
TI Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of
the Third International Workshop
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article; Proceedings Paper
CT 3rd International Workshop on Asymptomatic Primary Hyperparathyroidism
CY MAY 13, 2008
CL Orlando, FL
SP Endocrine Soc, Amer Assoc Clin Endocrinologists, Amer Soc Bone & Mineral Res, Canadian Soc Endorcrinol & Metabolism, Canadian Endocrine Update
ID VITAMIN-D INSUFFICIENCY; SERUM PARATHYROID-HORMONE;
MULTIPLE-ENDOCRINE-NEOPLASIA; FAMILIAL ISOLATED HYPERPARATHYROIDISM;
CARBOXYL-TERMINAL FRAGMENTS; BONE-MINERAL DENSITY; GERM-LINE MUTATIONS;
JAW TUMOR SYNDROME; D DEFICIENCY; SECONDARY HYPERPARATHYROIDISM
AB Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostic tests for this condition in clinical practice.
Participants: Interested professional societies selected a representative for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed. The conclusions were then circulated to the participating professional societies.
Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting.
Consensus Process: Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies.
Conclusions: We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second-and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) DNA sequence testing can be useful in familial hyperparathyroidism or hypercalcemia; 4) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 5) serum 25-hydroxyvitamin D levels should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; and 6) the estimated glomerular filtration rate should be used to determine the level of kidney function in PHPT: an estimated glomerular filtration rate of less than 60 ml/min . 1.73 m(2) should be a benchmark for decisions about surgery in established asymptomatic PHPT. (J Clin Endocrinol Metab 94: 340-350, 2009)
C1 [Eastell, R.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England.
[Arnold, A.] Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA.
[Arnold, A.] Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA.
[Brandi, M. L.] Univ Florence, Dept Internal Med, I-50133 Florence, Italy.
[Brown, E. M.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[D'Amour, P.] Hop St Luc, Ctr Hosp Univ Montreal, Res Ctr, Montreal, PQ H3C 3J7, Canada.
[Hanley, D. A.] Univ Calgary, Div Endocrinol & Metab, Dept Med, Calgary, AB T2N 1N4, Canada.
[Hanley, D. A.] Univ Calgary, Div Endocrinol & Metab, Dept Community Hlth Sci, Calgary, AB T2N 1N4, Canada.
[Hanley, D. A.] Univ Calgary, Div Endocrinol & Metab, Dept Oncol, Calgary, AB T2N 1N4, Canada.
[Rao, D. Sudhaker] Henry Ford Hosp, Bone & Mineral Res Lab, Detroit, MI 48202 USA.
[Rubin, M. R.; Silverberg, S. J.] Columbia Univ Coll Phys & Surg, Div Endocrinol, New York, NY 10032 USA.
[Goltzman, D.] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada.
McGill Univ, Ctr Hlth, Montreal, PQ H3G 1A4, Canada.
[Marx, S. J.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Peacock, M.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA.
[Mosekilde, L.] Aarhus Univ Hosp, Dept Endocrinol, DK-8000 Aarhus, Denmark.
[Bouillon, R.] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, B-3001 Louvain, Belgium.
[Lewiecki, E. M.] Univ New Mexico, Sch Med, New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM 87106 USA.
RP Eastell, R (reprint author), No Gen Hosp, Acad Unit Bone Metab, Metab Bone Ctr, Sorby Wing, Herries Rd, Sheffield S5 7AU, S Yorkshire, England.
EM r.eastell@sheffield.ac.uk
RI Eastell, Richard/G-5851-2011
OI Eastell, Richard/0000-0002-0323-3366
NR 84
TC 166
Z9 172
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
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2009
VL 94
IS 2
BP 340
EP 350
DI 10.1210/jc.2008-1758
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 403HC
UT WOS:000263072700003
PM 19193909
ER
PT J
AU Moore, AF
Jablonski, KA
Mason, CC
McAteer, JB
Arakaki, RF
Goldstein, BJ
Kahn, SE
Kitabchi, AE
Hanson, RL
Knowler, WC
Florez, JC
AF Moore, Allan F.
Jablonski, Kathleen A.
Mason, Clinton C.
McAteer, Jarred B.
Arakaki, Richard F.
Goldstein, Barry J.
Kahn, Steven E.
Kitabchi, Abbas E.
Hanson, Robert L.
Knowler, William C.
Florez, Jose C.
CA Diabet Prevention Program Res Grp
TI The Association of ENPP1 K121Q with Diabetes Incidence Is Abolished by
Lifestyle Modification in the Diabetes Prevention Program
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MEMBRANE GLYCOPROTEIN PC-1; INSULIN-RESISTANCE; GENETIC SUSCEPTIBILITY;
NO EVIDENCE; POLYMORPHISM; GLUCOSE; OBESITY; VARIANTS; RECEPTOR; RISK
AB Context: Insulin resistance is an important feature of type 2 diabetes. Ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin signaling, and a recent meta-analysis reported a nominal association between the Q allele in the K121Q(rs1044498) single nucleotide polymorphism in its gene ENPP1 and type 2 diabetes.
Objective and Intervention: We examined the impact of this polymorphism on diabetes incidence as well as insulin secretion and sensitivity at baseline and after treatment with a lifestyle intervention or metformin vs. placebo in the Diabetes Prevention Program (DPP).
Design, Setting, Participants, and Outcome: We genotyped ENPP1 K121Q in 3548 DPP participants and performed Cox regression analyses using genotype, intervention, and interactions as predictors of diabetes incidence.
Results: Fasting glucose and glycated hemoglobin were higher in QQ homozygotes at baseline (P < 0.001 for both). There was a significant interaction between genotype at rs1044498 and intervention under the dominant model (P = 0.03). In analyses stratified by treatment arm, a positive association with diabetes incidence was found in Q allele carriers compared to KK homozygotes [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.08-1.76; P = 0.009] in the placebo arm (n = 996). Lifestyle modification eliminated this increased risk. These findings persisted after adjustment for body mass index and race/ethnicity. Association of ENPP1 K121Q genotype with diabetes incidence under the additive and recessive genetic models showed consistent trends [HR, 1.10(95% CI, 0.99-1.23), P = 0.08; and HR, 1.16 (95% CI, 0.92-1.45), P = 0.20, respectively] but did not reach statistical significance.
Conclusions: ENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk. (J Clin Endocrinol Metab 94: 449-455, 2009)
C1 [Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Moore, Allan F.; McAteer, Jarred B.; Florez, Jose C.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Moore, Allan F.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Mason, Clinton C.; Hanson, Robert L.; Knowler, William C.] NIDDKD, Phoenix, AZ 85014 USA.
[Arakaki, Richard F.] Univ Hawaii, Dept Med Diabet & Endocrinol, Honolulu, HI 96813 USA.
[Goldstein, Barry J.] Thomas Jefferson Univ, Jefferson Med Coll, Div Endocrinol Diabet & Metab Dis, Philadelphia, PA 19107 USA.
[Kahn, Steven E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Kitabchi, Abbas E.] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA.
RP Florez, JC (reprint author), George Washington Univ, Diabet Prevent Program, Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM dppmail@biostat.bsc.gwu.edu
RI Hanson, Robert/O-3238-2015;
OI Hanson, Robert/0000-0002-4252-7068; Kahn, Steven/0000-0001-7307-9002
FU National Institutes of Health [R01 DK072041, K23 DK65978-05]; Indian
Health Service; Office of Research on Minority Health; National
Institute of Child Health and Human Development; National Institute on
Aging, the Centers for Disease Control and Prevention; Office of
Research on Women's Health; American Diabetes Association
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health provided funding to the
clinical centers and the Coordinating Center for the design and conduct
of the study and for collection, management, analysis, and
interpretation of the data. The Southwestern American Indian Centers
were supported directly by the NIDDK and the Indian Health Service. The
General Clinical Research Center Program, National Center for Research
Resources, supported data collection at many of the clinical centers.
Funding for data collection and participant support was also provided by
the Office of Research on Minority Health, the National Institute of
Child Health and Human Development, the National Institute on Aging, the
Centers for Disease Control and Prevention, Office of Research on
Women's Health, and the American Diabetes Association. Bristol-Myers
Squibb and Parke-Davis provided medication. This research was also
supported, in part, by the intramural research program of the NIDDK.
LifeScan Inc., Health-O-Meter, Hoechst Marion Roussel, Inc., Merck-Medco
Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast
Foods Co., and Quaker Oats Co. donated materials, equipment, or
medicines for concomitant conditions. McKesson BioServices Corp.,
Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided
support services under subcontract with the Coordinating Center. The
opinions expressed are those of the investigators and do not necessarily
reflect the views of the Indian Health Service or other funding
agencies. A complete list of centers, investigators, and staff can be
found in the Appendix(published as supplemental data on The Endocrine
Society's Journals Online web site at http://jcem.endojournals.org).
NR 36
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U1 0
U2 0
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 FEB
PY 2009
VL 94
IS 2
BP 449
EP 455
DI 10.1210/jc.2008-1583
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 403HC
UT WOS:000263072700019
PM 19017751
ER
PT J
AU Maggio, M
Ceda, GP
Lauretani, F
Bandinelli, S
Metter, EJ
Artoni, A
Gatti, E
Ruggiero, C
Guralnik, JM
Valenti, G
Ling, SM
Basaria, S
Ferrucci, L
AF Maggio, Marcello
Ceda, Gian Paolo
Lauretani, Fulvio
Bandinelli, Stefania
Metter, E. Jeffrey
Artoni, Andrea
Gatti, Elisa
Ruggiero, Carmelinda
Guralnik, Jack M.
Valenti, Giorgio
Ling, Shari M.
Basaria, Shehzad
Ferrucci, Luigi
TI Estradiol and Inflammatory Markers in Older Men
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ELDERLY-MEN; SERUM TESTOSTERONE; SEX-HORMONES; ASSOCIATION; ESTROGEN;
DISEASE; MUSCLE; HYPERESTROGENEMIA; INTERLEUKIN-6; INCHIANTI
AB Background: Aging is characterized by a mild proinflammatory state. In older men, low testosterone levels have been associated with increasing levels of proinflammatory cytokines. It is still unclear whether estradiol (E2), which generally has biological activities complementary to testosterone, affects inflammation.
Methods: We analyzed data obtained from 399 men aged 65-95 yr enrolled in the Invecchiare in Chianti study with complete data on body mass index (BMI), serum E2, testosterone, IL-6, soluble IL-6 receptor, TNF-alpha, IL-1 receptor antagonist, and C-reactive protein. The relationship between E2 and inflammatory markers was examined using multivariate linear models adjusted for age, BMI, smoking, physical activity, chronic disease, and total testosterone.
Results: In age-adjusted analysis, log (E2) was positively associated with log (IL-6) (r=0.19; P=0.047), and the relationship was statistically significant (P=0.032) after adjustments for age, BMI, smoking, physical activity, chronic disease, and serum testosterone levels. Log ( E2) was not significantly associated with log (C-reactive protein), log (soluble IL-6 receptor), or log (TNF-alpha) in both age-adjusted and fully adjusted analyses.
Conclusions: In older men, E2 is weakly positively associated with IL-6, independent of testosterone and other confounders including BMI. (J Clin Endocrinol Metab 94: 518-522, 2009)
C1 [Maggio, Marcello; Ceda, Gian Paolo; Artoni, Andrea; Gatti, Elisa; Valenti, Giorgio] Univ Hosp Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Unit, Geriatr Rehabil Dept, I-43100 Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil, I-50122 Florence, Italy.
[Metter, E. Jeffrey; Ruggiero, Carmelinda; Ling, Shari M.; Basaria, Shehzad; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Aging Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Basaria, Shehzad] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol,Bayview Med Ctr, Baltimore, MD 21224 USA.
RP Ferrucci, L (reprint author), NIA, NIH, NIA ASTRA Unit, Harbor Hosp, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM marcellomaggio2001@yahoo.it; ferruccilu@grc.nia.nih.gov
RI Lauretani, Fulvio/K-5115-2016
OI Ceda, Gian Paolo/0000-0002-9648-8295; Lauretani,
Fulvio/0000-0002-5287-9972
FU Italian Ministry of Health; U. S. National Institute on Aging
[N01-AG-916413, N01-AG-821336]; Intramural Research Program of the U. S.
National Institute on Aging [263 MD 9164 13, 263 MD 821336]; [ICS
110.1/RS97.71]
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the U.
S. National Institute on Aging (contracts N01-AG-916413 and
N01-AG-821336) and by the Intramural Research Program of the U. S.
National Institute on Aging (contracts 263 MD 9164 13 and 263 MD
821336). None of the sponsoring institutions interfered with the
collection, presentation, or interpretation of the data reported here.
NR 29
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U1 2
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 FEB
PY 2009
VL 94
IS 2
BP 518
EP 522
DI 10.1210/jc.2008-0940
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 403HC
UT WOS:000263072700029
PM 19050054
ER
PT J
AU Semple, RK
Sleigh, A
Murgatroyd, PR
Adams, CA
Bluck, L
Jackson, S
Vottero, A
Kanabar, D
Charlton-Menys, V
Durrington, P
Soos, MA
Carpenter, TA
Lomas, DJ
Cochran, EK
Gorden, P
O'Rahilly, S
Savage, DB
AF Semple, Robert K.
Sleigh, Alison
Murgatroyd, Peter R.
Adams, Claire A.
Bluck, Les
Jackson, Sarah
Vottero, Alessandra
Kanabar, Dipak
Charlton-Menys, Valentine
Durrington, Paul
Soos, Maria A.
Carpenter, T. Adrian
Lomas, David J.
Cochran, Elaine K.
Gorden, Phillip
O'Rahilly, Stephen
Savage, David B.
TI Postreceptor insulin resistance contributes to human dyslipidemia and
hepatic steatosis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TYROSINE KINASE DOMAIN; RECEPTOR GENE; PHOSPHOINOSITIDE 3-KINASE; PLASMA
ADIPONECTIN; CLINICAL-COURSE; ADIPOSE-TISSUE; FATTY LIVER; MUTATIONS;
SUFFICIENT; TRIGLYCERIDE
AB Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.
C1 [Semple, Robert K.; Adams, Claire A.; Soos, Maria A.; O'Rahilly, Stephen; Savage, David B.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England.
[Sleigh, Alison; Carpenter, T. Adrian] Univ Cambridge, Addenbrookes Hosp, Wolfson Brain Imaging Ctr, Cambridge CB2 0QQ, England.
[Murgatroyd, Peter R.] Addenbrookes Hosp, Wellcome Trust Clin Res Facil, Cambridge, England.
[Bluck, Les; Jackson, Sarah] MRC Human Nutr Res, Cambridge, England.
[Vottero, Alessandra] Univ Parma, Dept Pediat, I-43100 Parma, Italy.
[Kanabar, Dipak] Evalina Childrens Hosp, London, England.
[Charlton-Menys, Valentine; Durrington, Paul] Univ Manchester, Cardiovasc Res Grp, Core Technol Facil, Manchester, Lancs, England.
[Lomas, David J.] Univ Cambridge, Addenbrookes Hosp, Dept Radiol, Cambridge CB2 0QQ, England.
[Cochran, Elaine K.; Gorden, Phillip] NIDDK, Clin Endocrinol Branch, Bethesda, MD USA.
RP Semple, RK (reprint author), Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Hills Rd, Cambridge CB2 0QQ, England.
EM rksl6@cam.ac.uk; dbs23@medschl.cam.ac.uk
OI Semple, Robert/0000-0001-6539-3069; Sleigh, Alison/0000-0002-3859-8701;
LOMAS, David/0000-0003-2904-8617
FU Wellcome Trust [080952/Z/06/Z, 078986/Z/06/Z]; GlaxoSmithKline; United
Kingdom NIHR Cambridge Biomedical Research Centre; United Kingdom
Medical Research Council Centre for Obesity and Related Metabolic
Diseases
FX This work was supported by grants from the Wellcome Trust (to R.K.
Semple: intermediate Clinical Fellowship 080952/Z/06/Z; to S. O'Rahilly:
Programme Grant 078986/Z/06/Z), GlaxoSmithKline (to D.B. Savage: GSK
Clinical Fellowship), the United Kingdom NIHR Cambridge Biomedical
Research Centre, and the United Kingdom Medical Research Council Centre
for Obesity and Related Metabolic Diseases.
NR 40
TC 143
Z9 147
U1 0
U2 8
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2009
VL 119
IS 2
BP 315
EP 322
DI 10.1172/JCI37432
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 403LP
UT WOS:000263084400012
PM 19164855
ER
PT J
AU Widemann, BC
Goodspeed, W
Goodwin, A
Fojo, T
Balis, FM
Fox, E
AF Widemann, Brigitte C.
Goodspeed, Wendy
Goodwin, Anne
Fojo, Tito
Balis, Frank M.
Fox, Elizabeth
TI Phase I Trial and Pharmacokinetic Study of Ixabepilone Administered
Daily for 5 Days in Children and Adolescents With Refractory Solid
Tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 13-17, 2005
CL Orlando, FL
SP Amer Soc Clin Oncol
ID EPOTHILONE-B-ANALOG; METASTATIC BREAST-CANCER; CLINICAL-TRIAL;
PEDIATRIC-PATIENTS; PROSTATE-CANCER; DAILY SCHEDULE; BMS-247550;
CHEMOTHERAPY; ONCOLOGY; TAXANE
AB Purpose
The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary response rate for ixabepilone, a microtubule-stabilizing agent, administered intravenously daily for 5 days in children and adolescents.
Patients and Methods
Patients >= 2 and <= 18 years with relapsed or refractory solid tumors were enrolled onto sequential cohorts to the following five dose levels: 3.0 (n = 3), 4.5 (n = 4), 6.0 (n = 3), 8.0 (n = 6), and 10 (n = 3) mg/m(2)/d. Eligibility criteria, dose levels, definitions of DLT and MTD, and pharmacokinetic sampling times were designed to be as similar as possible to the adult phase I trial of ixabepilone on the same schedule.
Results
Nineteen children (median age, 10 years; range, 2 to 18 years) were enrolled, and 18 (12 with sarcomas) were assessable for toxicity. DLTs (grade 4 neutropenia for > 5 days and grade 3 fatigue) were observed in two of three patients receiving 10 mg/m(2)/d. The MTD of ixabepilone administered daily for 5 days every 21 days was 8 mg/m(2)/d. Myelosuppression, GI, and hepatic toxicities were common non-DLTs. Peripheral neuropathy was uncommon. Ixabepilone clearance was 475 +/- 247 mL/min/m(2), volume of distribution at steady-state was 12.2 +/- 5.4 L/kg, and half-life was 14 hours.
Conclusion
The recommended dose of ixabepilone for phase II trials in solid tumors is 8 mg/m(2)/d daily for 5 days every 21 days. This dose is 33% higher than the MTD in adults receiving the same dosing schedule. Pharmacokinetic parameters in children and adolescents were highly variable but similar to adults.
C1 [Widemann, Brigitte C.; Goodspeed, Wendy; Goodwin, Anne; Fojo, Tito; Balis, Frank M.; Fox, Elizabeth] NCI, Pediat & Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10-Rm 1-5742, Bethesda, MD 20892 USA.
EM widemanb@mail.nih.gov
FU Intramural NIH HHS
NR 26
TC 7
Z9 7
U1 0
U2 0
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 FEB 1
PY 2009
VL 27
IS 4
BP 550
EP 556
DI 10.1200/JCO.2008.17.6644
PG 7
WC Oncology
SC Oncology
GA 400UK
UT WOS:000262894400013
PM 19075272
ER
PT J
AU Freidlin, B
Korn, EL
AF Freidlin, Boris
Korn, Edward L.
TI Monitoring for Lack of Benefit: A Critical Component of a Randomized
Clinical Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PHASE-III TRIAL; ADVANCED PANCREATIC-CANCER; COOPERATIVE-ONCOLOGY-GROUP;
SURGICAL ADJUVANT BREAST; NECK-CANCER; PLUS GEMCITABINE; BOWEL PROJECT;
DOUBLE-BLIND; RADIOTHERAPY; COMBINATION
AB To balance patient interests against the need for acquiring evidence, ongoing randomized clinical trials are formally monitored for early convincing indication of benefit or lack of benefit. In lethal diseases like cancer, where new therapies are often toxic and may have limited preliminary efficacy data, monitoring for lack of benefit is particularly important. We review the complex nature of stopping a randomized trial for lack of benefit and argue that many cancer trials could be improved by a more aggressive approach to monitoring. On the other hand, we caution that some commonly used monitoring guidelines may result in stopping for lack of benefit even when a nontrivial beneficial effect is observed.
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA.
RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, EPN 8122, Bethesda, MD 20892 USA.
EM freidlinb@ctep.nci.nih.gov
NR 45
TC 18
Z9 18
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2009
VL 27
IS 4
BP 629
EP 633
DI 10.1200/JCO.2008.17.8905
PG 5
WC Oncology
SC Oncology
GA 400UK
UT WOS:000262894400024
PM 19064977
ER
PT J
AU de Gonzalez, AB
Jee, SH
Engels, EA
AF de Gonzalez, Amy Berrington
Jee, Sun-Ha
Engels, Eric A.
TI No Association Between Hepatitis B and Pancreatic Cancer in a
Prospective Study in Korea
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID VIRUS
C1 [de Gonzalez, Amy Berrington; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Jee, Sun-Ha] Yonsei Univ, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea.
RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 7
TC 5
Z9 5
U1 0
U2 0
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 FEB 1
PY 2009
VL 27
IS 4
BP 648
EP 648
DI 10.1200/JCO.2008.20.7514
PG 1
WC Oncology
SC Oncology
GA 400UK
UT WOS:000262894400035
PM 19103724
ER
PT J
AU van Noord, C
Straus, SMJM
Sturkenboom, MCJM
Hofman, A
Aarnoudse, AJLHJ
Bagnardi, V
Kors, JA
Newton-Cheh, C
Witteman, JCM
Stricker, BHC
AF van Noord, Charlotte
Straus, Sabine M. J. M.
Sturkenboom, Miriam C. J. M.
Hofman, Albert
Aarnoudse, Albert-Jan L. H. J.
Bagnardi, Vincenzo
Kors, Jan A.
Newton-Cheh, Christopher
Witteman, Jacqueline C. M.
Stricker, Bruno H. C.
TI Psychotropic Drugs Associated With Corrected QT Interval Prolongation
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE QTc interval; psychotropic drugs; electrocardiography; arrhythmia
ID TORSADE-DE-POINTES; LEFT-VENTRICULAR HYPERTROPHY; NON-ANTIARRHYTHMIC
DRUGS; MYOCARDIAL-INFARCTION; HEART-FAILURE; ROTTERDAM; RISK;
POPULATION; ELECTROCARDIOGRAMS; REPOLARIZATION
AB Aims: To study whether listed putative corrected QT (QTc)-prolonging psychotropic drugs indeed prolong the QTc interval under everyday circumstances and to evaluate whether this is a class effect or an individual drue effect. we conducted a prospective population-based cohort study.
Methods: This study was conducted as part of the Rotterdam Study and included 3377 men and 4845 women (>= 55 years) who had triennial electrocardiograms (ECGs). The primary end point,; of the study were the length of the QTc interval at each ECG. the difference in QTc interval between consecutive ECGs within one person, and the risk of ail abnormally prolonged QTc interval. Drug use at the index date was obtained from automated dispensing records. The associations were examined by means of a repeated measurement analysis, adjusted for age. sex, diabetes mellitus. hypertension, myocardial infarction, heart failure. and use of class I QTc-prolonging drugs.
Results: Of the 8222 participants. 813 participants (9.9%) developed QTc prolongation during follow-up and 492 participants (74.4% women) used psychotropic drugs at the time of an ECG. Starting tricyclic antidepressants increased the QTc interval significantly with 6.9 milliseconds (95% confidence interval [CI], 3.1-10.7 milliseconds) between consecutive ECGs in comparison With Consecutive ECGs of participants not using tricyclic antidepressants. in particular starting amitriptyline (8.5 milliseconds: 95% CI. 2.8-14.2 milliseconds), maprotiline (13.9 milliseconds: 9 % CI, 3.6-24.3 milliseconds), and nortriptyline (35.3 milliseconds: 95% CI. 8.0-62.6 milliseconds). Starting lithium also increased the QTc interval significantly (18.6 milliseconds; 95% Cl 4.8-32.4 milliseconds).
Conclusions: In this population-based prospective cohort Stud),, we confirmed the importance of antidepressants and antipsychotics as potential contributors to QTc prolongation. Especially, starting tricyclic antidepressant drugs (as a class) is associated with a significant intraindividual increase in the QTc interval in comparison to the change in nonusers. The tricyclic antidepressants seem to prolong the QTc interval as a class effect.
C1 [van Noord, Charlotte; Straus, Sabine M. J. M.; Sturkenboom, Miriam C. J. M.; Hofman, Albert; Aarnoudse, Albert-Jan L. H. J.; Witteman, Jacqueline C. M.; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[van Noord, Charlotte; Straus, Sabine M. J. M.] Dutch Med Evaluat Board, The Hague, Netherlands.
[Aarnoudse, Albert-Jan L. H. J.; Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands.
[Bagnardi, Vincenzo] Univ Milano Bicocca, Dept Stat, Milan, Italy.
[Bagnardi, Vincenzo] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, England.
[Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
[Newton-Cheh, Christopher] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, Dr Molewaterpl 50,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM b.stricker@erasmusmc.nl
NR 39
TC 49
Z9 49
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD FEB
PY 2009
VL 29
IS 1
BP 9
EP 15
DI 10.1097/JCP.0b013e318191c6a8
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 395YA
UT WOS:000262558200003
PM 19142100
ER
PT J
AU Becker, RE
Greig, NH
AF Becker, Robert E.
Greig, Nigel H.
TI Neuropsychiatric Clinical Trials Should They Accommodate Real-World
Practices or Set Standards for Clinical Practices?
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Review
DE clinical trials; errors; biases; real world conditions; protocol
standards
ID SAMPLE-SIZE REQUIREMENTS; EVIDENCE-BASED MEDICINE; ALZHEIMERS-DISEASE;
MEASUREMENT ERROR; COGNITIVE IMPAIRMENT; ROFECOXIB LITIGATION;
PLACEBO-RESPONSE; DRUG DEVELOPMENT; DOUBLE-BLIND; DEPRESSION
AB Evidence-based psychiatry seeks the best research evidence for use in patient care. Recent research Suggests that problems with accuracy, precision, bias, and other sources, of unreliability potentially interfere with the validity of psychiatry's evidence base. Because many negative clinical research studies go Unpublished, awareness and fuller understanding of these problems are blocked by lack of access to relevant data. Based on the importance of scientific soundness of neuropsychiatric research and patient care, we argue for increased attentiveness by investigators and practitioners to how clinical trials (CTs) interdependently estimate the efficacy of treatments and the effectiveness of methods as fair tests of efficacy. Deference by CT investigators to real-world practice conditions at research sites because of the unreliability introduced into data by these practices does not ensure unbiased evaluations of treatment efficacy. We argue for more systematic attention to sources of unreliability in CT investigations and increased commitments to assure the validity of the neuropsychiatric evidence base. These recommendations aim to determine neuropsychiatric drug efficacy with greater certainty to better quantify the clinical importance of drug-associated effects and to provide CT-evidenced guidance for practitioners to most effectively use drug efficacy in patient care.
C1 [Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 5th Floor BRC Bldg,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rebecker2008@comcast.net
FU National Institute on Aging, National Institutes of Health
FX The authors are supported in part by the Intramural Research program of
the National Institute on Aging, National Institutes of Health. The
authors have received no other funding for this work and have no
financial conflicts of interest. The views expressed within this article
are those of the authors and may not represent those of the National
Institute on Aging, National Institutes of Health.
NR 73
TC 8
Z9 8
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD FEB
PY 2009
VL 29
IS 1
BP 56
EP 64
DI 10.1097/JCP.0b013e318192e2fa
PG 9
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 395YA
UT WOS:000262558200013
PM 19142109
ER
PT J
AU Paukner, A
Huntsberry, ME
Suomi, SJ
AF Paukner, Annika
Huntsberry, Mary E.
Suomi, Stephen J.
TI Tufted Capuchin Monkeys (Cebus apella) Spontaneously Use Visual but Not
Acoustic Information to Find Hidden Food Items
SO JOURNAL OF COMPARATIVE PSYCHOLOGY
LA English
DT Article
DE foraging choices; visual information; acoustic information; capuchin
monkey; inferential reasoning
ID TOOL USE; INFERENCES; LOCATION
AB Foraging choices in tufted capuchins monkeys are guided by perceptual, cognitive, and motivational factors, but little is known about how these factors might interact. The present study investigates how different types of sensory information affect capuchins' ability to locate hidden food. In two experiments, capuchins were presented with two cups, one baited and one empty. Monkeys were given visual, acoustic, or acoustic-visual information related to the baited cup, the empty cup, or both baited and empty cup. Results show that capuchins spontaneously used visual information to locate food, and that information indicating presence and absence of food led to higher success rates than information indicating only absence of food. In contrast, acoustic information did not lead to success rates above chance levels and failed to enhance performance in combination with visual information. Capuchins spontaneously avoided a visually empty cup, but they did not appear to associate sounds with either the presence or absence of food. Being able to locate food items with the aid of acoustic cues might be a learned process that requires interactive experiences with the task's contingencies.
RP Paukner, A (reprint author), NIH, Comparat Ethol Lab, Anim Ctr, POB 529, Poolesville, MD 20837 USA.
EM pauknera@mail.nih.gov
FU Division of Intramural Research, National Institute of Child Health and
Human Development
FX This research was supported by funds from the Division of Intramural
Research, National Institute of Child Health and Human Development. We
thank Pier Ferrari for critical comments on earlier drafts of this
article.
NR 21
TC 24
Z9 24
U1 0
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7036
J9 J COMP PSYCHOL
JI J. Comp. Psychol.
PD FEB
PY 2009
VL 123
IS 1
BP 26
EP 33
DI 10.1037/a0013128
PG 8
WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology
SC Behavioral Sciences; Psychology; Zoology
GA 410WX
UT WOS:000263610100004
PM 19236142
ER
PT J
AU Li, LP
AF Li, Leping
TI GADEM: A Genetic Algorithm Guided Formation of Spaced Dyads Coupled with
an EM Algorithm for Motif Discovery
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE ChIP; de novo motif discovery; expectation-maximization; genetic
algorithm; k-mer; spaced dyad
ID EMBRYONIC STEM-CELLS; FACTOR-BINDING-SITES; GENOME-WIDE ANALYSIS;
REGULATORY ELEMENTS; CHROMATIN-IMMUNOPRECIPITATION; NONCODING SEQUENCES;
MULTIPLE SEQUENCES; DNA; PATTERNS; IDENTIFICATION
AB Genome-wide analyses of protein binding sites generate large amounts of data; a ChIP dataset might contain 10,000 sites. Unbiased motif discovery in such datasets is not generally feasible using current methods that employ probabilistic models. We propose an efficient method, GADEM, which combines spaced dyads and an expectation-maximization ( EM) algorithm. Candidate words (four to six nucleotides) for constructing spaced dyads are prioritized by their degree of overrepresentation in the input sequence data. Spaced dyads are converted into starting position weight matrices (PWMs). GADEM then employs a genetic algorithm (GA), with an embedded EM algorithm to improve starting PWMs, to guide the evolution of a population of spaced dyads toward one whose entropy scores are more statistically significant. Spaced dyads whose entropy scores reach a pre-specified significance threshold are declared motifs. GADEM performed comparably with MEME on 500 sets of simulated "ChIP" sequences with embedded known P53 binding sites. The major advantage of GADEM is its computational efficiency on large ChIP datasets compared to competitors. We applied GADEM to six genome-wide ChIP datasets. Approximately, 15 to 30 motifs of various lengths were identified in each dataset. Remarkably, without any prior motif information, the expected known motif ( e. g., P53 in P53 data) was identified every time. GADEM discovered motifs of various lengths (6-40 bp) and characteristics in these datasets containing from 0.5 to > 13 million nucleotides with run times of 5 to 96 h. GADEM can be viewed as an extension of the well-known MEME algorithm and is an efficient tool for de novo motif discovery in large-scale genome-wide data. The GADEM software is available at www.niehs.nih.gov/research/resources/software/GADEM/.
C1 Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Li, LP (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
EM li3@niehs.nih.gov
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [ES101765- 05]
FX We thank David Umbach and Grace Kissling for discussions and careful
reading of the manuscript. We thank Clare Weinberg and Shyamal Peddada
for discussions. We thank the reviewers for their thought provoking
comments. We thank Robert Bass for creating the GADEM web site and the
Computational Biology Facility at NIEHS for computing time. This
research was supported by Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences to L. L. ( ES101765-
05).
NR 51
TC 48
Z9 50
U1 0
U2 4
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 FEB
PY 2009
VL 16
IS 2
BP 317
EP 329
DI 10.1089/cmb.2008.16TT
PG 13
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 403BS
UT WOS:000263057400016
PM 19193149
ER
PT J
AU Joiner, WM
Shelhamer, M
AF Joiner, Wilsaan M.
Shelhamer, Mark
TI A model of time estimation and error feedback in predictive timing
behavior
SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE Prediction; Saccade; Timing; Error feedback
ID SACCADIC EYE-MOVEMENTS; INTERNAL CLOCK; PARKINSONS-DISEASE;
PHASE-TRANSITIONS; SYNCHRONIZATION STRATEGIES; TEMPORAL DISCRIMINATION;
STIMULUS SEQUENCE; THEORETICAL-MODEL; BASAL GANGLIA; HUMAN BRAIN
AB Two key features of sensorimotor prediction are preprogramming and adjusting of performance based on previous experience. Oculomotor tracking of alternating visual targets provides a simple paradigm to study this behavior in the motor system; subjects make predictive eye movements (saccades) at fast target pacing rates (> 0.5 Hz). In addition, the initiation errors (latencies) during predictive tracking are correlated over a small temporal window (correlation window) suggesting that tracking performance within this time range is used in the feedback process of the timing behavior. In this paper, we propose a closed-loop model of this predictive timing. In this model, the timing between movements is based on an internal estimation of stimulus timing (an internal clock), which is represented by a (noisy) signal integrated to a threshold. The threshold of the integrate-to-fire mechanism is determined by the timing between movements made within the correlation window of previous performance and adjusted by feedback of recent and projected initiation error. The correlation window size increases with repeated tracking and was estimated by two independent experiments. We apply the model to several experimental paradigms and show that it produces data specific to predictive tracking: a gradual shift from reaction to prediction on initial tracking, phase transition and hysteresis as pacing frequency changes, scalar property, continuation of predictive tracking despite perturbations, and intertrial correlations of a specific form. These results suggest that the process underlying repetitive predictive motor timing is adjusted by the performance and the corresponding errors accrued over a limited time range and that this range increases with continued confidence in previous performance.
C1 [Joiner, Wilsaan M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Shelhamer, Mark] Johns Hopkins Univ Hosp, Sch Med, Dept Biomed Engn, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
RP Joiner, WM (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM joinerw@nei.nih.gov
FU NIH [T32MH20069, EY015193]; NSF [BCS-0615106]
FX The study was supported by NIH T32MH20069 and EY015193 and NSF
BCS-0615106.
NR 82
TC 9
Z9 9
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5313
J9 J COMPUT NEUROSCI
JI J. Comput. Neurosci.
PD FEB
PY 2009
VL 26
IS 1
BP 119
EP 138
DI 10.1007/s10827-008-0102-x
PG 20
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA 407QI
UT WOS:000263379000008
PM 18563546
ER
PT J
AU Kong, H
Kim, Y
Lee, Y
Ch, B
Jung, S
Jung, Y
Kim, YM
AF Kong, Hyesik
Kim, Youngsoo
Lee, Yonghyun
Choi, Boim
Jung, Sunhwa
Jung, Yunjin
Kim, Young Mi
TI Sulfate-conjugated methylprednisolone: Evaluation as a colon-specific
methylprednisolone prodrug and comparison with sulfate-conjugated
prednisolone and dexamethasone
SO JOURNAL OF DRUG TARGETING
LA English
DT Article
DE Colon-specific prodrug; methylprednisolone; sulfation; sulfate
conjugates; drug delivery; glucocorticoid
ID INFLAMMATORY-BOWEL-DISEASE; STEADY-STATE PHARMACOKINETICS; IN-VITRO
PROPERTIES; 21-SULFATE SODIUM; POTENTIAL PRODRUGS; DRUG-DELIVERY; RATS;
COLITIS
AB Methylprednisolone 21-sulfate sodium (MPS) was prepared and evaluated as a colon-specific methylprednisolone prodrug and its colon-specific property was compared with prednisolone 21-sulfate sodium (PDS) and dexamethasone 21-sulfate sodium (DS), reported previously as colon-specific prodrugs of the glucocorticoids. The synthetic process and yield of MPS was simple and high. The apparent partition coefficient of methylprednisolone (MP) was greatly reduced by sulfate conjugation. The sulfate conjugates MPS, PDS, and DS were (bio)chemically stable in the homogenates of the upper intestine. In marked contrast, the sulfate conjugates were deconjugated to liberate the corresponding glucocorticoids in the cecal contents. Although the rates of deconjugation were not significantly different, the corresponding glucocorticoids were accumulated with distinct profiles depending on the metabolic susceptibility of the unconjugated glucocorticoids to microbial reductase(s). Upon oral administration of the sulfate conjugates to rats, the plasma concentrations of the conjugates were extremely low and the urinary recoveries were less than 5% of the doses. These results suggest that, like PDS and DS, MPS administered orally is delivered efficiently to the large intestine followed by deconjugation to liberate MP and the metabolic susceptibility of the unconjugated glucocorticoids may affect therapeutic availability of the sulfate conjugates.
C1 [Kim, Youngsoo; Lee, Yonghyun; Jung, Sunhwa; Jung, Yunjin] Pusan Natl Univ, Coll Pharm, Lab Biomed Chem, Pusan 609735, South Korea.
[Kong, Hyesik] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Choi, Boim; Kim, Young Mi] Pusan Natl Univ, Coll Pharm, Med Chem Lab, Pusan 609735, South Korea.
RP Jung, Y (reprint author), Pusan Natl Univ, Coll Pharm, Lab Biomed Chem, Pusan 609735, South Korea.
EM jungy@pusan.ac.kr; ymikim@pusan.ac.kr
FU Pusan National University research grant
FX This work was supported for two years by the Pusan National University
research grant.
NR 17
TC 8
Z9 10
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1061-186X
J9 J DRUG TARGET
JI J. Drug Target.
PD FEB
PY 2009
VL 17
IS 2
BP 159
EP 167
DI 10.1080/10611860802546637
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 453EO
UT WOS:000266593200008
PM 18988065
ER
PT J
AU Singh, SR
Hou, SX
AF Singh, Shree Ram
Hou, Steven X.
TI Multipotent stem cells in the Malpighian tubules of adult Drosophila
melanogaster
SO JOURNAL OF EXPERIMENTAL BIOLOGY
LA English
DT Review
DE kidney; Malpighian tubules; kidney development; multipotent stem cells;
renal and nephric stem cells; renal cancer; Drosophila melanogaster
ID RENAL PROGENITOR CELLS; SIDE POPULATION CELLS; KIDNEY DEVELOPMENT;
EPITHELIAL-CELLS; SELF-RENEWAL; POSTISCHEMIC KIDNEY; SIGNALING PATHWAYS;
JAK/STAT PATHWAY; MODEL ORGANISMS; GROWTH-FACTOR
AB Excretion is an essential process of an organism's removal of the waste products of metabolism to maintain a constant chemical composition of the body fluids despite changes in the external environment. Excretion is performed by the kidneys in vertebrates and by Malpighian tubules (MTs) in Drosophila. The kidney serves as an excellent model organ to investigate the cellular and molecular mechanisms underlying organogenesis. Mammals and Drosophila share common principles of renal development. Tissue homeostasis, which is accomplished through self-renewal or differentiation of stem cells, is critical for the maintenance of adult tissues throughout the lifetime of an animal. Growing evidence suggests that stem cell self-renewal and differentiation is controlled by both intrinsic and extrinsic factors. Deregulation of stem cell behavior results in cancer formation, tissue degeneration, and premature aging. The mammalian kidney has a low rate of cellular turnover but has a great capacity for tissue regeneration following an ischemic injury. However, there is an ongoing controversy about the source of regenerating cells in the adult kidney that repopulate injured renal tissues. Recently, we identified multipotent stem cells in the MTs of adult Drosophila and found that these stem cells are able to proliferate and differentiate in several types of cells in MTs. Furthermore, we demonstrated that an autocrine JAK-STAT (Janus kinase-signal transducers and activators of transcription) signaling regulates stem cell self-renewal or differentiation of renal stem cells. The Drosophila MTs provide an excellent in vivo system for studying the renal stem cells at cellular and molecular levels. Understanding the molecular mechanisms governing stem cell self-renewal or differentiation in vivo is not only crucial to using stem cells for future regenerative medicine and gene therapy, but it also will increase our understanding of the mechanisms underlying cancer formation, aging and degenerative diseases. Identifying and understanding the cellular processes underlying the development and repair of the mammalian kidney may enable more effective, targeted therapies for acute and chronic kidney diseases in humans.
C1 [Singh, Shree Ram; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Ft Detrick, MD 21702 USA.
RP Hou, SX (reprint author), NCI, Mouse Canc Genet Program, NIH, Ft Detrick, MD 21702 USA.
EM hous@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU National Institutes of Health; National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. Deposited in
PMC for release after 12 months.
NR 103
TC 18
Z9 20
U1 1
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0022-0949
J9 J EXP BIOL
JI J. Exp. Biol.
PD FEB 1
PY 2009
VL 212
IS 3
BP 413
EP 423
DI 10.1242/jeb.024216
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 396HD
UT WOS:000262581900017
PM 19151216
ER
PT J
AU Cao, Y
Calafat, AM
Doerge, DR
Umbach, DM
Bernbaum, JC
Twaddle, NC
Ye, XY
Rogan, WJ
AF Cao, Yang
Calafat, Antonia M.
Doerge, Daniel R.
Umbach, David M.
Bernbaum, Judy C.
Twaddle, Nathan C.
Ye, Xiaoyun
Rogan, Walter J.
TI Isoflavones in urine, saliva, and blood of infants: data from a pilot
study on the estrogenic activity of soy formula
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE phytoestrogen; isoflavone; genistein; daidzein; infant feeding; soy
formula
ID HUMAN-MILK; PHYTOESTROGENS; GENISTEIN; DAIDZEIN; PHARMACOKINETICS;
CONSUMPTION; EXCRETION; EXPOSURE; PROTEIN; PLASMA
AB In the United States, about 25% of infant formula sold is based on soy protein, which is an important source of estrogenic isoflavones in the human food supply. Nevertheless, few studies report isoflavone levels in infants. We did a partly cross-sectional and partly longitudinal pilot study to examine children's exposure to isoflavones from different feeding methods. A total of 166 full-term infants between birth and 1 year of age were recruited into soy formula, cow milk formula, or breast milk regimens according to their feeding histories. A total of 381 urine, 361 saliva, and 88 blood samples were collected at 382 visits. We used automated online solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for measuring three isoflavones ( daidzein, genistein, and equol) in urine, and used similar LC/MS/MS techniques for saliva and blood spots. Concentrations of daidzein and genistein were undetectable in most blood or saliva samples from children fed breast milk or cow milk formula. The proportion of non-detectable values was somewhat lower in urine than in the other matrices. Concentrations of equol were detectable only in a few urine samples. For both daidzein and genistein, urine contained the highest median concentrations, followed by blood and then saliva. Urinary concentrations of genistein and daidzein were about 500 times higher in the soy formula-fed infants than in the cow milk formula-fed infants. The correlations between matrices for either analyte were strikingly lower than the correlation between the two analytes in any single matrix. We did not find significant correlations between isoflavone concentrations and the levels of certain hormones in children fed soy formula. Our results, based on much larger numbers of infants, strongly confirm previous reports, but whether phytoestrogens in soy formula are biologically active in infants is still an open question. We plan further longitudinal studies focusing on physical and developmental findings reflecting the effects of estrogen exposure.
C1 [Cao, Yang; Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Doerge, Daniel R.; Twaddle, Nathan C.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Bernbaum, Judy C.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,FedEx UPS 111 TW Alexa, Res Triangle Pk, NC 27709 USA.
EM rogan@niehs.nih.gov
RI Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
FU Intramural NIH HHS [Z99 ES999999]
NR 31
TC 65
Z9 70
U1 8
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD FEB
PY 2009
VL 19
IS 2
BP 223
EP 234
DI 10.1038/jes.2008.44
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 395CT
UT WOS:000262500600007
PM 18665197
ER
PT J
AU Maras, JE
Newby, PK
Bakun, PJ
Ferrucci, L
Tucker, KL
AF Maras, Janice E.
Newby, P. K.
Bakun, Peter J.
Ferrucci, Luigi
Tucker, Katherine L.
TI Whole grain intake: The Baltimore Longitudinal Study of Aging
SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS
LA English
DT Article
DE Whole grains; Wheat; Bran; Germ; Fiber; Database; Food composition
ID CARDIOVASCULAR-DISEASE; DIETARY FIBER; RISK-FACTORS; HEALTH;
CONSUMPTION; CANCER; MEN
AB Our objective was to identify major dietary Sources of whole grains and to describe the construction of a database of whole grain content of foods. Dietary information was collected with 7-d food records from men and women in the Baltimore Longitudinal Study of Aging, mean age 62.1 +/- 16.0 years, who participated in the dietary assessment portion of the study (n = 1516), and estimates of whole grain intake were obtained from a newly developed database. The Pyramid Servings database and 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) recipe ingredients database were then used to calculate both servings and gram weights of whole grain intakes. Mean intakes of whole grains, refined grains, and total grains, as well as frequency of intake for major whole grain food groups and whole grain content for each group, were calculated. Top contributors of whole grains were ready-to-eat breakfast cereals (made with whole grain as well as bran), hot breakfast cereals (made with whole grain), multi-grain bread, and whole wheat bread. While more research is needed to better understand the benefits of whole grains, the development of research tools, including databases to accurately assess whole grain intake, is a critical step in completing such research. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Maras, Janice E.; Bakun, Peter J.; Tucker, Katherine L.] Tufts Univ, Dietary Assessment & Epidemiol Res Program, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Newby, P. K.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
[Newby, P. K.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
[Ferrucci, Luigi] NIA, Baltimore Longitudinal Study Aging, Baltimore, MD 21224 USA.
RP Tucker, KL (reprint author), Tufts Univ, Dietary Assessment & Epidemiol Res Program, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM Katherine.tucker@tufts.edu
RI Tucker, Katherine/A-4545-2010;
OI Tucker, Katherine/0000-0001-7640-662X
FU NIA NIH HHS [Z01 AG000015-50]
NR 26
TC 12
Z9 14
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 0889-1575
J9 J FOOD COMPOS ANAL
JI J. Food Compos. Anal.
PD FEB
PY 2009
VL 22
IS 1
BP 53
EP 58
DI 10.1016/j.jfca.2008.10.005
PG 6
WC Chemistry, Applied; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 430KW
UT WOS:000264989000008
PM 20126297
ER
PT J
AU Arora, NK
Gustafson, DH
AF Arora, Neeraj K.
Gustafson, David H.
TI Perceived Helpfulness of Physicians' Communication Behavior and Breast
Cancer Patients' Level of Trust Over Time
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE breast cancer; trust; patient-physician communication; longitudinal
analysis
ID FUNCTIONAL ASSESSMENT; CARE; QUALITY; RELIABILITY; VALIDATION; SUPPORT;
SCALE; WOMEN
AB We evaluated the association between physicians' communication behavior and breast cancer patients' trust in their physicians.
Longitudinal survey conducted at baseline, 2-month, and 5-month follow-up during first year of diagnosis.
Newly diagnosed breast cancer patients (N = 246).
We collected data on patient perceptions of the helpfulness of informational, emotional, and decision-making support provided by physicians and patients' trust. Linear regression models evaluated the association of concurrent and prior levels of physician support with patients' trust.
At baseline, patients who received helpful informational, emotional, and decision-making support from physicians reported greater trust (p < 0.05, p < 0.001, and p < 0.01, respectively). At the 2-month assessment, baseline informational support and informational and emotional support at 2-months were associated with greater trust (p < 0.05, p < 0.01, and p < 0.05, respectively). At the 5-month assessment, only helpful emotional support from physicians at 5 months was associated with greater trust (p < 0.01). Interestingly, while perceived helpfulness of all three types of physician support decreased significantly over time, patient trust remained high and unchanged.
Findings suggest that while informational and decision-making support may be more important to patient trust early in the course of treatment, emotional support from physicians may be important to maintain trust throughout the initial year of diagnosis.
C1 [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Gustafson, David H.] Univ Wisconsin, Ctr Hlth Enhancement Syst Studies, Madison, WI USA.
RP Arora, NK (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Executive Blvd,MSC 7344,Execut Plaza N 4005, Bethesda, MD 20892 USA.
EM aroran@mail.nih.gov
FU National Institute of Child Health and Human Development; National
Cancer Institute [5R01HD32922]
FX This research was supported by the National Institute of Child Health
and Human Development and the National Cancer Institute under grant no.
5R01HD32922: PI: David H. Gustafson.
NR 19
TC 13
Z9 16
U1 1
U2 6
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 FEB
PY 2009
VL 24
IS 2
BP 252
EP 255
DI 10.1007/s11606-008-0880-x
PG 4
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 397GO
UT WOS:000262651100016
PM 19089501
ER
PT J
AU Grady, KI
Ulisney, KI
Kirklin, JK
Naftel, DC
Gelijns, AC
Young, JB
Martin, T
Chisholm, K
Moskowitz, A
AF Grady, K. I.
Ulisney, K. I.
Kirklin, J. K.
Naftel, D. C.
Gelijns, A. C.
Young, J. B.
Martin, T.
Chisholm, K.
Moskowitz, A.
TI Important Improvements in Quality of Life after MCSD Implant: First
Results from INTERMACS
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Grady, K. I.; Moskowitz, A.] Northwestern Univ, Med Ctr, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA.
[Ulisney, K. I.] Natl Heart Lung & Blood Inst, Bethesda, MD USA.
[Kirklin, J. K.; Naftel, D. C.] Univ Alabama, Birmingham, AL USA.
[Gelijns, A. C.] Columbia Univ, Med Ctr, New York, NY USA.
[Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Martin, T.] Newark Beth Israel Hosp, Newark, NJ USA.
[Chisholm, K.] Univ Arizona, Med Ctr, Tucson, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
MA 408
BP S207
EP S207
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800405
ER
PT J
AU Holman, WI
Kirklin, JK
Naftel, DC
Kormos, RL
Desvign-Nickens, P
Camucho, M
Ascheim, D
AF Holman, W. I.
Kirklin, J. K.
Naftel, D. C.
Kormos, R. L.
Desvign-Nickens, P.
Camucho, M.
Ascheim, D.
TI Early Infections after MCSD Implant In 455 Patients: Incidence, Location
and Outcome
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Holman, W. I.; Kirklin, J. K.; Naftel, D. C.; Kormos, R. L.] Univ Alabama, Birmingham, AL USA.
[Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Desvign-Nickens, P.] NHLBI, Bethesda, MD 20892 USA.
[Camucho, M.] Newark Beth Israel Med Ctr, Newark, NJ USA.
[Ascheim, D.] Columbia Univ, New York, NY USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
MA 254
BP S155
EP S155
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800254
ER
PT J
AU Kormos, RL
Teuteberg, JJ
Kirklin, JK
Naftel, DC
Stevenson, LW
Milano, CA
Miller, MA
Pagani, FD
Rogers, JG
Aaronson, KD
AF Kormos, R. L.
Teuteberg, J. J.
Kirklin, J. K.
Naftel, D. C.
Stevenson, L. W.
Milano, C. A.
Miller, M. A.
Pagani, F. D.
Rogers, J. G.
Aaronson, K. D.
TI Adverse Event (AE) Rates In Patients Receiving Pulsatile VAD's:
Incidence and Composition Change Dramatically 3 Months after Implant
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Kormos, R. L.; Teuteberg, J. J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kirklin, J. K.; Naftel, D. C.] Univ Alabama, Birmingham, AL USA.
[Stevenson, L. W.] Brigham & Womens Med Ctr, Boston, MA USA.
[Milano, C. A.; Rogers, J. G.] Duke Univ, Med Ctr, Durham, NC USA.
[Miller, M. A.] NHLBI, Bethesda, MD 20892 USA.
[Rogers, J. G.; Aaronson, K. D.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
MA 416
BP S210
EP S210
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800412
ER
PT J
AU Kormos, RL
Kirklin, JK
Naftel, DG
Young, JB
Acker, M
Jessup, M
Jeevanandam, V
Baldwin, TL
Camacho, M
Ascheim, DD
AF Kormos, R. L.
Kirklin, J. K.
Naftel, D. G.
Young, J. B.
Acker, M.
Jessup, M.
Jeevanandam, V.
Baldwin, T. L.
Camacho, M.
Ascheim, D. D.
TI Early Neurological Adverse Events (NAE) after Pulsatile VAD implantation
in 455 Patients: Incidence, Severity and Outcome
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kirklin, J. K.; Naftel, D. G.] Univ Alabama, Birmingham, AL USA.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Young, J. B.; Acker, M.; Jessup, M.] Univ Penn, Philadelphia, PA USA.
[Jeevanandam, V.] Univ Chicago, Chicago, IL 60637 USA.
[Baldwin, T. L.] NHLBI, Bethesda, MD 20892 USA.
[Camacho, M.] Newark Beth Israel Med Ctr, Newark, NJ USA.
[Ascheim, D. D.] Columbia Univ, New York, NY USA.
NR 0
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 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
MA 181
BP S129
EP S129
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800181
ER
PT J
AU Pipeling, MR
Whitlock, AB
Migueles, SA
Connors, M
McDyer, JF
AF Pipeling, M. R.
Whitlock, A. B.
Migueles, S. A.
Connors, M.
McDyer, J. F.
TI Striking Expansion and Persistence of T-bet(+)CD8(+) CMV-Specific T
Cells with Primary Infection in Lung Transplant Recipients
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Pipeling, M. R.; Whitlock, A. B.; McDyer, J. F.] Johns Hopkins Univ, Baltimore, MD USA.
[Migueles, S. A.; Connors, M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
SU S
MA 539
BP S253
EP S253
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800535
ER
PT J
AU Ulisney, KL
Grady, KL
Kirklin, JK
Naftet, DC
Gelijns, AC
Moskowitz, AJ
Young, JB
Myers, SL
Wissman, SA
AF Ulisney, K. L.
Grady, K. L.
Kirklin, J. K.
Naftet, D. C.
Gelijns, A. C.
Moskowitz, A. J.
Young, J. B.
Myers, S. L.
Wissman, S. A.
TI Evaluating Quality of Life Prior to MCSD Implant Is a Challenge: Results
from INTERMACS
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 29th Annual Meeting and Scientific Session of the
International-Society-for-Heart-and-Lung-Transplantation
CY APR 22-25, 2009
CL Paris, FRANCE
SP Int Soc Heart & Lung Transplantat
C1 [Ulisney, K. L.] NHLBI, Bethesda, MD 20892 USA.
[Grady, K. L.] Northwestern Univ, Med Ctr, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA.
[Kirklin, J. K.; Naftet, D. C.; Myers, S. L.] Univ Alabama, Birmingham, AL USA.
[Gelijns, A. C.; Moskowitz, A. J.] Columbia Univ, Med Ctr, New York, NY USA.
[Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Wissman, S. A.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD FEB
PY 2009
VL 28
IS 2
MA 587
BP S269
EP S270
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 409XT
UT WOS:000263539800583
ER
PT J
AU Otoo, GE
Lartey, AA
Perez-Escamilla, R
AF Otoo, Gloria E.
Lartey, Anna A.
Perez-Escamilla, Rafael
TI Perceived Incentives and Barriers to Exclusive Breastfeeding Among
Periurban GhanaianWomen
SO JOURNAL OF HUMAN LACTATION
LA English
DT Article
DE Africa; exclusive breastfeeding; Ghana; incentives; barriers; focus
groups
ID INSUFFICIENT MILK; MOTHERS; AFRICA; COMMUNITY
AB Focus group discussions were conducted to elicit the perceived incentives and barriers to exclusive breastfeeding in Ghana Thirty-five breastfeeding women were recruited from the Manya and Yilo Krobo districts of the eastern region. Participants had a mean age of 2.75 years and had at least one child < a months old. Almost all of the participants believed that exclusive breastfeeding is the superior infant feeding method and should be practiced for the first c months postpartum. However there was widespread belief that infants can be given water if it is clean. Mothers reported that exclusive breastfeeding was easier when breast milk began to flow soon after delivery. The main obstacles to exclusive breastfeeding identified were maternal employment, breast and nipple problems, perceived milk insufficiency, and pressure from family. Addressing the concerns put forward by these participants can be used to enhance exclusive breastfeeding promotion in this region. J Hum Lact. 25(1):34-41.
C1 [Otoo, Gloria E.] Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
[Lartey, Anna A.] Univ Ghana, Dept Nutr & Food Sci, Legon, Ghana.
[Perez-Escamilla, Rafael] NIH, EXPORT CEHDL, Bethesda, MD USA.
RP Otoo, GE (reprint author), Univ Connecticut, Dept Nutr Sci, 3624 Horsebarn Hill Rd Ext, Storrs, CT 06269 USA.
FU NIH/NICHD [HD43620]
FX This project was funded by the RIING Project through NIH/NICHD grant
HD43620. The authors acknowledge the participation of all mothers in
this study. They are grateful to Deda Ogum Mary Ohipeni Richlove
Ocansey, and Emelia Asamoah for the assistance with the focus group
discussions.
NR 22
TC 17
Z9 17
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0890-3344
J9 J HUM LACT
JI J. Hum. Lact.
PD FEB
PY 2009
VL 25
IS 1
BP 34
EP 41
DI 10.1177/0890334408325072
PG 8
WC Nursing; Obstetrics & Gynecology; Pediatrics
SC Nursing; Obstetrics & Gynecology; Pediatrics
GA 403ZP
UT WOS:000263120800010
PM 18971507
ER
PT J
AU Pacheco-Rodriguez, G
Kumaki, F
Steagall, WK
Zhang, Y
Ikeda, Y
Lin, JP
Billings, EM
Moss, J
AF Pacheco-Rodriguez, Gustavo
Kumaki, Fumiyuki
Steagall, Wendy K.
Zhang, Yi
Ikeda, Yoshihiko
Lin, Jing-Ping
Billings, Eric M.
Moss, Joel
TI Chemokine-Enhanced Chemotaxis of Lymphangioleiomyomatosis Cells with
Mutations in the Tumor Suppressor TSC2 Gene
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TUBEROUS
SCLEROSIS COMPLEX; CHEMOKINE/CHEMOKINE RECEPTOR NOMENCLATURE;
BREAST-CANCER METASTASIS; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; STROMAL
FIBROBLASTS; POLYMORPHISM; EXPRESSION; LYMPHANGIOMYOMATOSIS
AB Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by LAM cells (smooth-muscle-like cells) that have mutations in the tumor suppressor genes tuberous sclerosis complex (TSC) 1 or 2 and have the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of CCL2, CXCL1, and CXCL5 were significantly higher in samples from LAM patients than those from healthy volunteers. In vitro, CCL2 or MCP-1 induced selective migration of cells, showing loss of heterozygosity of TSC2 from a heterogeneous population of cells grown from explanted LAM lungs. Additionally, the frequencies of single-nucleotide polymorphisms in the CCL2 gene promoter region differed significantly in LAM patients and healthy volunteers (p = 0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. The presence (i.e., potential functionality) of chemokine receptors was evaluated using immunohistochemistry in lung sections from 30 LAM patients. Expression of chemokines and these receptors varied among LAM patients and differed from that seen in some cancers (e.g., breast cancer and melanoma cells). These observations are consistent with the notion that chemokines such as CCL2 may serve to determine mobility and specify the site of metastasis of the LAM cell. The Journal of Immunology, 2009, 182: 1270-1277.
C1 [Pacheco-Rodriguez, Gustavo; Kumaki, Fumiyuki; Steagall, Wendy K.; Zhang, Yi; Ikeda, Yoshihiko; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jing-Ping] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Billings, Eric M.] NHLBI, Integrat Computat Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
FU National Institutes of Health; National Heart, Lung, and Blood
Institute; Oak Ridge Institute for Science and Education
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood
Institute. Y.I. was contracted through a Senior Fellowship from the Oak
Ridge Institute for Science and Education.
NR 62
TC 26
Z9 27
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 FEB 1
PY 2009
VL 182
IS 3
BP 1270
EP 1277
PG 8
WC Immunology
SC Immunology
GA 400BD
UT WOS:000262842100009
PM 19155472
ER
PT J
AU Eberly, MD
Kader, M
Hassan, W
Rogers, KA
Zhou, JZ
Mueller, YM
Mattapallil, MJ
Piatak, M
Lifson, JD
Katsikis, PD
Roederer, M
Villinger, F
Mattapallil, JJ
AF Eberly, Matthew D.
Kader, Muhamuda
Hassan, Wail
Rogers, Kenneth A.
Zhou, Jianzhong
Mueller, Yvonne M.
Mattapallil, Mary J.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Katsikis, Peter D.
Roederer, Mario
Villinger, Francois
Mattapallil, Joseph J.
TI Increased IL-15 Production Is Associated with Higher Susceptibility of
Memory CD4 T Cells to Simian Immunodeficiency Virus during Acute
Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NONHUMAN-PRIMATES; RHESUS MACAQUES; SIV INFECTION; HOMEOSTATIC
PROLIFERATION; LYMPHOCYTE-PROLIFERATION; ACTIVATION; EXPRESSION;
INDUCTION; CYTOKINE; TYPE-1
AB Acute SIV infection is characterized by explosive infection of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T cells are infected until as late as days 7-8 after challenge. However, by day 10 postinfection, most of the memory CD4 T cells are infected and carry viral DNA. The rapidity with which infection expands within 2-3 days to encompass virtually the entire memory CD4 T cell compartment suggests significant alterations in the susceptibility of memory CD4 T cells to infection during this period. The mechanism(s) underlying this increased permissiveness to infection is not known. In this study, we show that IL-15 secretion significantly correlates with the up-regulated expression of CD4 on memory CD4 T cells that is associated with increased permissiveness to SIV infection. Activation and proliferation of memory CD8, but not memory CD4 T cells, preceded the amplification of viral infection. Although memory CD4 T cells did not express normal activation markers, they displayed a significant up-regulation in the density of CD4 but not CCR5 expression between days 7 and 10 postinfection that correlated with increased plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells with IL-15 and/or SIV was associated with a significant increase in the expression of CD4 and infection of these sorted cells. Our results demonstrate that IL-15 contributes to the increased susceptibility of memory CD4 T cells to SIV during the early phase of acute SIV infection. The Journal of Immunology, 2009, 182: 1439-1448.
C1 [Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Rogers, Kenneth A.; Zhou, Jianzhong; Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Mueller, Yvonne M.; Katsikis, Peter D.] Drexel Univ, Coll Med, Philadelphia, PA 19129 USA.
[Mattapallil, Mary J.] NEI, NIH, Bethesda, MD 20892 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Room B4068, Bethesda, MD 20814 USA.
EM jmattapallil@usuhs.mil
FU National Institutes of Allergy and Infectious Diseases [K22 AI07812];
National Institute of Dental and Craniofacial Research [R21 DE018339];
National Institute of Allergy and Infectious Diseases [R01 AI062437];
National Cancer Institute, National Institutes of Health [NO1-CO-124000]
FX The described project was supported by Grant K22 AI07812 from the
National Institutes of Allergy and Infectious Diseases and Grant R21
DE018339 from the National Institute of Dental and Craniofacial Research
awarded to J.J.M. and in part from R01 AI062437 from the National
Institute of Allergy and Infectious Diseases awarded to P.D.K Studies
were supported in part with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract NO1-CO-124000.
NR 41
TC 35
Z9 35
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 FEB 1
PY 2009
VL 182
IS 3
BP 1439
EP 1448
PG 10
WC Immunology
SC Immunology
GA 400BD
UT WOS:000262842100028
PM 19155491
ER
PT J
AU Claudio, E
Sonder, SU
Saret, S
Carvalho, G
Ramalingam, TR
Wynn, TA
Chariot, A
Garcia-Perganeda, A
Leonardi, A
Paun, A
Chen, A
Ren, NY
Wang, HS
Siebenlist, U
AF Claudio, Estefania
Sonder, Soren Ulrik
Saret, Sun
Carvalho, Gabrielle
Ramalingam, Thirumalai R.
Wynn, Thomas A.
Chariot, Alain
Garcia-Perganeda, Antonio
Leonardi, Antonio
Paun, Andrea
Chen, Amy
Ren, Nina Y.
Wang, Hongshan
Siebenlist, Ulrich
TI The Adaptor Protein CIKS/Act1 Is Essential for IL-25-Mediated Allergic
Airway Inflammation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; IN-VIVO; NEGATIVE REGULATOR; GENE-EXPRESSION; IL-25; IL-17;
RECEPTOR; INTERLEUKIN-17; IDENTIFICATION; CYTOKINES
AB IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production, and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses that these two cytokines elicit. We identify CD11c(+) macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo. The Journal of Immunology, 2009, 182: 1617-1630.
C1 [Claudio, Estefania; Sonder, Soren Ulrik; Saret, Sun; Carvalho, Gabrielle; Chariot, Alain; Garcia-Perganeda, Antonio; Leonardi, Antonio; Paun, Andrea; Ren, Nina Y.; Wang, Hongshan; Siebenlist, Ulrich] NIH, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Ramalingam, Thirumalai R.; Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Amy] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Siebenlist, U (reprint author), NIH, Immunoregulat Lab, Bldg 10,Room 11B15, Bethesda, MD 20892 USA.
EM USiebenlist@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011;
OI LEONARDI, Antonio/0000-0001-8636-9623
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 39
TC 83
Z9 88
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 FEB 1
PY 2009
VL 182
IS 3
BP 1617
EP 1630
PG 14
WC Immunology
SC Immunology
GA 400BD
UT WOS:000262842100048
PM 19155511
ER
PT J
AU Garcia-Pineres, AJ
Hildesheim, A
Dodd, L
Kemp, TJ
Yang, J
Fullmer, B
Harro, C
Lowy, DR
Lempicki, RA
Pinto, LA
AF Garcia-Pineres, Alfonso J.
Hildesheim, Allan
Dodd, Lori
Kemp, Troy J.
Yang, Jun
Fullmer, Brandie
Harro, Clayton
Lowy, Douglas R.
Lempicki, Richard A.
Pinto, Ligia A.
TI Gene Expression Patterns Induced by HPV-16 L1 Virus-Like Particles in
Leukocytes from Vaccine Recipients
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; RANDOMIZED CONTROLLED-TRIAL; CELLULAR
IMMUNE-RESPONSES; BLOOD MONONUCLEAR-CELLS; NASOPHARYNGEAL CARCINOMA;
QUADRIVALENT VACCINE; SUSTAINED EFFICACY; ADULT VOLUNTEERS; DENDRITIC
CELLS; WHOLE-BLOOD
AB Human papillomavirus (HPV) virus-like particle (VLP) vaccines were recently licensed. Although neutralizing Ab titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMCs from 17 vaccine and 4 placebo recipients before vaccination and 1 mo after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, IFN, and cell cycle pathways in VLP-stimulated PBMCs. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for more than two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular, IFN-induced genes, was observed in PBMCs collected before vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response-related genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials. The Journal of Immunology, 2009, 182: 1706-1729.
C1 [Garcia-Pineres, Alfonso J.; Kemp, Troy J.; Pinto, Ligia A.] NCI, Sci Applicat Int Corp Frederick, HPV Immunol Lab, Frederick, MD 21702 USA.
[Hildesheim, Allan] NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Dodd, Lori] NIH, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Yang, Jun; Fullmer, Brandie; Lempicki, Richard A.] NCI, SAIC Frederick, Lab Bioinformat & Immunopathogenesis, Frederick, MD 21702 USA.
[Harro, Clayton] Johns Hopkins Univ, Ctr Immunizat Res, Baltimore, MD 21205 USA.
[Lowy, Douglas R.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pinto, LA (reprint author), NCI, Sci Applicat Int Corp Frederick, HPV Immunol Lab, Bldg 469,Room 120, Frederick, MD 21702 USA.
EM lpinto@ncifcrf.gov
RI Lempicki, Richard/E-1844-2012; Hildesheim, Allan/B-9760-2015
OI Lempicki, Richard/0000-0002-7059-409X; Hildesheim,
Allan/0000-0003-0257-2363
FU National Cancer Institute; National Institutes of Health [N01-CO-12400]
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health
(N01-CO-12400).
NR 53
TC 14
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 FEB 1
PY 2009
VL 182
IS 3
BP 1706
EP 1729
PG 24
WC Immunology
SC Immunology
GA 400BD
UT WOS:000262842100058
PM 19155521
ER
PT J
AU Inozume, T
Hanada, KI
Wang, QJ
Yang, JC
AF Inozume, Takashi
Hanada, Ken-ichi
Wang, Qiong J.
Yang, James C.
TI IL-17 Secreted by Tumor Reactive T Cells Induces IL-8 Release by Human
Renal Cancer Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE renal cell carcinoma; IL-17; IL-8; microenvironment
ID COLLAGEN-INDUCED ARTHRITIS; AUTOIMMUNE INFLAMMATION; INTERLEUKIN-17;
EXPRESSION; DISTINCT; ACTIVATION; PHENOTYPE; CYTOKINE; MELANOMA;
ANTIGENS
AB T(H)17 is a newly identified pathogenic memory CD4(+) T-cell lineage with potent agonist effects in some murine experimental autoimmunity models, however. its role in tumor immunology is still unclear. Clinical experience with interleukin (IL)-2 and ipilumumab [anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody], particularly in treating immunogenic malignancies Such as melanoma and renal cell carcinoma (RCC), has suggested an association between a variety Of autoimmune phenomena and tumor regression. To investigate this issue in patients with RCC, we isolated T-cell clones from peripheral blood that released IL-17 on stimulation with their autologous RCC tumor line. Clones were generated from I patient before any treatment by in vitro stimulation with dendritic cells, autologous tumor, and IL-2 in the presence of anti-CTLA4 antibody. That patient subsequently received treatment with ipilimumab and showed both objective tumor regression and immune-mediated colitis. Limiting dilution cloning of his tumor-dendritic cell-stimulated T cells produced the 3G8D CD4(+) clone, which secreted both IL-17 and interferon-gamma when cocultured with the autologous RCC line (transduced with class II transactivation Molecule to induce major histocompatibility complex-class 11 expression), Broader analysis of its cytokine secretion profile showed large amounts of IL-8 when cocultured with RCC. but not when triggered with phorbol 12-myristate 13-acetate and ionomycin. This led to the discovery that IL-8 was being produced by the RCC cells in response to T-cell-derived IL-17. This effect of exogeneous IL-17 on IL-8 release front tumor was seen in 5 of 8 RCCs, but not in other tumors tested. preliminary data on the frequency of IL-17-secreting T cells in the lymphocytes infiltrating RCCS Suggest that there may be a positive correlation between this frequeney and IL-8 production by nonlymphoid cells as determined by quantitative reverse transcription-polymerase chain reaction. This report extends the known bidirectional interactions between immune cells and malignant cells in the tumor microenvironment that can shape and modulate the host immune response to cancer.
C1 [Inozume, Takashi; Hanada, Ken-ichi; Wang, Qiong J.; Yang, James C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Yang, JC (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3W-3840, Bethesda, MD 20892 USA.
EM JamesYang@mail.nih.gov
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 28
TC 26
Z9 28
U1 0
U2 2
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 FEB-MAR
PY 2009
VL 32
IS 2
BP 109
EP 117
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 411NC
UT WOS:000263655300002
PM 19238009
ER
PT J
AU Singh, V
Ji, QY
Feigenbaum, L
Leighty, RM
Hurwitz, AA
AF Singh, Vinod
Ji, Qingyong
Feigenbaum, Lionel
Leighty, Robert M.
Hurwitz, Arthur A.
TI Melanoma Progression Despite Infiltration by In Vivo-primed
TRP-2-specific T Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE melanoma; T cells; adoptive immunotherapy; T-cell receptor transgene
ID TYROSINASE-RELATED PROTEIN-2; TUMOR-ANTIGEN; CANCER-IMMUNOTHERAPY;
CLONAL DELETION; TRANSGENIC MICE; SELF-ANTIGENS; B16 MELANOMA; LOW
AVIDITY; TOLERANCE; LYMPHOCYTES
AB Many antigens recognized by tumor-reactive cytotoxic CD8(+) T cells are self-antigens. Tyrosinase-related protein 2 (TRP-2) is a melanogenic enzyme expressed by both melanocytes and melanoma,.; that is reported to be a candidate melanoma rejection antigen. To study the role of self-reactive CD8(+) T cells in tumor immunity and autoimmunity, we generated mice that bear I T-cell receptor transgene (TCR Tg) specific for the TRP-2((180-188)) epitope. TRP-2 TCR Tg mice did not spontaneously develop depigmentation despite systemic expression of TRP-2 in the skin. Peripheral T cells from these TCR Tg mice exhibited a naive phenotype and proliferated in response to TRP-2 in vitro. In addition, transfer of in vitro-activated Tg T cells reduced 1316 Pulmonary tumor burden, but not subcutaneous tumors. We next sought to determine the in vivo responses or the Tg T cells to endogenous and tumor-derived TRP-2. Adoptive transfer of naive TCR Tg T cells into wild-type C57BL/6 mice, in combination with a TRP-2-pulsed dendritic cell vaccines induced proliferation of the Tg T cells and resulted in migration of the Tg T cells into a subcutaneous B16 melanoma tumor. Although these tumor-infiltrating Tg T cells remained reactive against TRP-2, they did not reduce growth of the primary subcutaneous tumor; similarly, these in vivo-primed effector cells had no significant effect on the growth of pulmonary nodules. These data demonstrate that despite in vivo priming, tumor-infiltrating T cells may fail to reduce tumor burden. Determining the basis for the inability of the tumor microenvironment to sustain effective antitumor responses will be critical for designing newer, more potent antitumor immunotherapies.
C1 [Singh, Vinod; Hurwitz, Arthur A.] NCI, Canc & Inflammat Program, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA.
[Leighty, Robert M.] NCI, Data Management Serv, Frederick, MD 21701 USA.
[Ji, Qingyong] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
RP Hurwitz, AA (reprint author), NCI, Canc & Inflammat Program, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA.
EM hurwitza@nciferf.gov
FU NCI, NIH
FX Supported by the Intramural Research Program, NCI, NIH.
NR 40
TC 21
Z9 21
U1 1
U2 4
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 FEB-MAR
PY 2009
VL 32
IS 2
BP 129
EP 139
PG 11
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 411NC
UT WOS:000263655300004
PM 19238011
ER
PT J
AU Vietri, NJ
Purcell, BK
Tobery, SA
Rasmussen, SL
Leffel, EK
Twenhafel, NA
Ivins, BE
Kellogg, MD
Webster, WM
Wright, ME
Friedlander, AM
AF Vietri, Nicholas J.
Purcell, Bret K.
Tobery, Steven A.
Rasmussen, Suzanne L.
Leffel, Elizabeth K.
Twenhafel, Nancy A.
Ivins, Bruce E.
Kellogg, Mark D.
Webster, Wendy M.
Wright, Mary E.
Friedlander, Arthur M.
TI A Short Course of Antibiotic Treatment Is Effective in Preventing Death
from Experimental Inhalational Anthrax after Discontinuing Antibiotics
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; IMMUNOGLOBULIN-G; PROPHYLAXIS;
PATHOGENESIS; ANTIBODIES; PATHOLOGY; OUTBREAK; VACCINE; SPORES
AB Background. Postexposure prophylaxis of inhalational anthrax requires prolonged antibiotic therapy or antibiotics and vaccination. The duration of treatment for established anthrax is controversial, because retained spores may germinate and cause disease after antibiotics are discontinued. Using rhesus macaques, we determined whether a short course of antibiotic treatment, as opposed to prophylaxis, could effectively treat inhalational anthrax and prevent disease caused by the germination of spores after discontinuation of antibiotics.
Methods. Two groups of 10 rhesus macaques were exposed to an aerosol dose of Bacillus anthracis spores. Animals in group 1 received ciprofloxacin prophylaxis beginning 1-2 h after exposure. Those in group 2 began receiving ciprofloxacin after becoming bacteremic, and treatment was continued for 10 days. When each group 2 animal completed 10 days of therapy, the prophylactic antibiotic was discontinued in the paired group 1 animal.
Results. In group 1 (prophylaxis), no deaths occurred during antibiotic treatment, but only 2 (20%) of 10 animals survived after antibiotics were discontinued. In contrast, in group 2 (treatment), 3 deaths occurred during antibiotic treatment, but all 7 animals (100%) alive after 10 days of therapy survived when antibiotics were discontinued.
Conclusions. In the treatment of inhalational anthrax, the prolonged course of antibiotics required to achieve prophylaxis may not be necessary to prevent anthrax that results from the germination of retained spores after the discontinuation of antibiotics.
C1 [Vietri, Nicholas J.; Purcell, Bret K.; Tobery, Steven A.; Rasmussen, Suzanne L.; Ivins, Bruce E.; Webster, Wendy M.] USA, Med Res Inst Infect Dis, Div Bacteriol, Frederick, MD 21702 USA.
[Twenhafel, Nancy A.] USA, Med Res Inst Infect Dis, Div Pathol, Frederick, MD 21702 USA.
[Kellogg, Mark D.] USA, Med Res Inst Infect Dis, Div Diagnost Syst, Frederick, MD 21702 USA.
[Leffel, Elizabeth K.] USA, Med Res Inst Infect Dis, Ctr Aerobiol Sci, Frederick, MD 21702 USA.
[Wright, Mary E.] NIAID, Bethesda, MD 20892 USA.
RP Vietri, NJ (reprint author), USA, Med Res Inst Infect Dis, Div Bacteriol, 1425 Porter St, Frederick, MD 21702 USA.
EM nicholas.vietri@amedd.army.mil; arthur.friedlander@amedd.army.mil
OI Kellogg, Mark/0000-0003-1868-2153
NR 30
TC 16
Z9 16
U1 0
U2 1
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 FEB 1
PY 2009
VL 199
IS 3
BP 336
EP 341
DI 10.1086/596063
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 392UB
UT WOS:000262326600007
PM 19099484
ER
PT J
AU Safaeian, M
Falk, RT
Rodriguez, AC
Hildesheim, A
Kemp, T
Williams, M
Morera, L
Barrantes, M
Herrero, R
Porras, C
Pinto, L
AF Safaeian, Mahboobeh
Falk, Roni T.
Rodriguez, Ana Cecilia
Hildesheim, Allan
Kemp, Troy
Williams, Marcus
Morera, Lidiana
Barrantes, Manuel
Herrero, Rolando
Porras, Carolina
Pinto, Ligia
TI Factors Associated with Fluctuations in IgA and IgG Levels at the Cervix
during the Menstrual Cycle
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 24th International Papillomavirus Conference and Clinical Workshop
CY NOV 03-09, 2007
CL Beijing, PEOPLES R CHINA
ID PARTICLE VACCINE; YOUNG-WOMEN; SECRETIONS; MUCUS; IMMUNOGLOBULINS;
INFECTION; CYTOKINES; EFFICACY; TYPE-18; SERUM
AB Objective. The objective of this analysis was to describe patterns and determinants of cervical immunoglobulin A (IgA) and G (IgG) levels during the menstrual cycle.
Methods. A total of 154 women who attended 3 visits coinciding with the follicular, periovulatory, and luteal phases of their menstrual cycle were studied. Cervical secretions were collected at each visit for determination of total IgA and IgG levels. Questionnaires administered at each visit inquired about demographic characteristics and behavioral practices.
Results. Total IgA and IgG levels were higher among oral contraceptive (OC) users than among naturally cycling women ( hereafter, "non-OC users"). IgA and IgG levels decreased at midcycle, particularly among non-OC users. After adjustment for phase of the current cycle, specimen weight, and detection of blood in the sample, report of a recent illness was associated with lower IgA and IgG levels and increased age with higher IgA and IgG levels among OC users and non-OC users. Increased lifetime number of pregnancies was associated with a higher IgA level among non-OC users and a higher IgG level among OC users. Change in immunoglobulin levels between visits was associated with sample weight and the presence of blood for both OC users and non-OC users.
Conclusions. Phase of the current menstrual cycle and OC use were significant determinants of cervical IgA and IgG levels. The impacts of endogenous and exogenous hormones on cervical immunoglobulin levels should be further investigated.
C1 [Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD 20852 USA.
[Kemp, Troy; Williams, Marcus; Pinto, Ligia] NCI, HPV Immunol Lab, SAIC Frederick, Frederick, MD USA.
[Rodriguez, Ana Cecilia; Morera, Lidiana; Barrantes, Manuel; Herrero, Rolando; Porras, Carolina] Fdn INCIENSA, San Jose, Costa Rica.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, NIH, 6120 Execut Blvd,Ste 550, Rockville, MD 20852 USA.
EM safaeianm@mail.nih.gov
RI 段, 沛沛/C-9902-2010; Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU Intramural NIH HHS [Z99 CA999999, ZIA CP010216-4]; NCI NIH HHS
[N01CO12400]
NR 22
TC 12
Z9 12
U1 0
U2 0
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 FEB 1
PY 2009
VL 199
IS 3
BP 455
EP 463
DI 10.1086/596060
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 392UB
UT WOS:000262326600024
PM 19133811
ER
PT J
AU Leppert, IR
Almli, CR
McKinstry, RC
Mulkern, RV
Pierpaoli, C
Rivkin, MJ
Pike, GB
AF Leppert, Ilana R.
Almli, C. Robert
McKinstry, Robert C.
Mulkern, Robert V.
Pierpaoli, Carlo
Rivkin, Michael J.
Pike, G. Bruce
CA Brain Dev Cooperative Grp
TI T-2 Relaxometry of Normal Pediatric Brain Development
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE T-2 relaxometry; pediatric; brain development; myelination; multicenter
ID MAGNETIC-RESONANCE; WHITE-MATTER; RELAXATION-TIMES; MR ASSESSMENT; NIH
MRI; 1.5 T; MATURATION; MYELINATION; AGE; INFANTS
AB Purpose: To establish normal age-related changes in the magnetic resonance (MR) T-2 relaxation time constants of brain using data collected as part of the National Institutes of Health (NIH) MRI Study of Normal Brain Development.
Materials and Methods: This multicenter study of normal brain and behavior development provides both longitudinal and cross-sectional data, and has enabled us to investigate T2 evolution in several brain regions in healthy children within the age range of birth through 4 years 5 months. Due to the multicenter nature of the study and the extended period of data collection, periodically scanned inanimate and human phantoms were used to assess intra- and intersite variability.
Results: The main finding of this work. based on over 340 scans, is the identification and parameterization of the monoexponential evolution of T2 from birth through 4 years 5 months of age in various brain structures.
Conclusion: The exponentially decaying T2 behavior is believed to reflect the rapid changes in water content as well as myelination during brain development. The data will become publicly available as part of a normative pediatric MRI and clinical/behavioral database, thereby providing a basis for comparison in studies assessing normal brain development, and studies of deviations due to various neurological, neuropsychiatric, and developmental disorders.
C1 [Leppert, Ilana R.; Pike, G. Bruce] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
[Almli, C. Robert] Washington Univ, Sch Med, Dept Neurol, Program Neurosci,Dev Neuropsychobiol Lab, St Louis, MO 63110 USA.
[McKinstry, Robert C.] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[McKinstry, Robert C.] Washington Univ, Med Ctr, St Louis Childrens Hosp, St Louis, MO 63110 USA.
[Mulkern, Robert V.] Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Pierpaoli, Carlo] NICHHD, NIH, Bethesda, MD 20892 USA.
[Rivkin, Michael J.] Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Rivkin, Michael J.] Harvard Univ, Childrens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Rivkin, Michael J.] Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Leppert, IR (reprint author), McGill Univ, Montreal Neurol Inst, 3801 Univ St,WB325, Montreal, PQ H3A 2B4, Canada.
EM ilana@bic.mni.mcgill.ca
RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011; Pike,
Bruce/K-5562-2014;
OI Pike, Bruce/0000-0001-8924-683X; Freund, Lisa/0000-0003-2095-4023;
Gwinn, Katrina/0000-0002-8277-651X
FU NIH
FX We thank the NIH contracting officers for their support. We also
acknowledge the important contribution and remarkable spirit of John
Haselgrove, PhD (deceased). The views expressed in this article do not
necessarily represent the official views of the National Institute of
Mental Health, the National Institute of Child Health and Human
Development, the National Institute on Drug Abuse, the National
Institute of Neurological Disorders and Stroke, the National Institutes
of Health, the U.S. Department of Health and Human Services, or the
United States government.
NR 39
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Z9 32
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD FEB
PY 2009
VL 29
IS 2
BP 258
EP 267
DI 10.1002/jmri.21646
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 399SJ
UT WOS:000262819300002
PM 19161173
ER
PT J
AU Farasat, S
Wei, MH
Herman, M
Liewehr, DJ
Steinberg, SM
Bale, SJ
Fleckman, P
Toro, JR
AF Farasat, S.
Wei, M-H
Herman, M.
Liewehr, D. J.
Steinberg, S. M.
Bale, S. J.
Fleckman, P.
Toro, J. R.
TI Novel transglutaminase-1 mutations and genotype-phenotype investigations
of 104 patients with autosomal recessive congenital ichthyosis in the
USA
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID BATHING SUIT ICHTHYOSIS; HUMAN GENETIC-DISEASE; LAMELLAR ICHTHYOSIS;
KERATINOCYTE TRANSGLUTAMINASE; HARLEQUIN ICHTHYOSIS; NONSENSE MUTATIONS;
TRANSPORTER ABCA12; PRENATAL EXCLUSION; MISSENSE MUTATION; JAPANESE
PATIENT
AB Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1 (TGase-1), are one of the causes of ARCI.
Methods: The TGM1 mutation spectrum was characterised and genotype-phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA.
Methods: Germline mutations in TGM1 were identified in 55% (57/104) of patients with ARCI. Arginine residues in TGase-1 were mutated in 39% (22/57) of patients overall and 54% (20/37) of those with missense mutations. In total, 55% (12/22) of missense mutations were within CpG dinucleotides and 92% (11/12) of these mutations were C-->T or G-->A transitions. The genotype-phenotype investigation found that ARCI with TGM1 mutations was significantly associated with presence of collodion membrane at birth (p = 0.006), ectropion (p = 0.001), plate-like scales (p = 0.005) and alopecia (p = 0.001). Patients who had at least one mutation predicted to truncate TGase-1 were more likely to have more severe hypohidrosis (p = 0.001) and overheating (p = 0.0007) at onset of symptoms than were those with exclusively TGM1 missense mutations. A logistic model was developed, which predicted that individuals with collodion membrane, alopecia and/or eye problems are about four times more likely to have TGM1 mutations than patients without these findings.
Conclusion: This is the largest investigation of patients with ARCI to date. It expands the TGM1 mutation spectrum and confirms that despite genetic and phenotypic heterogeneity in ARCI, TGM1 is the main causative gene for this disorder. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of CpG dinucleotides.
C1 [Farasat, S.; Herman, M.; Toro, J. R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wei, M-H] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
[Liewehr, D. J.; Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bale, S. J.] GeneDx Inc, Gaithersburg, MD USA.
[Fleckman, P.] Univ Washington, Div Dermatol, Seattle, WA 98195 USA.
RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA.
EM toroj@mail.nih.gov
FU National Institutes of Health (NIH); Pfizer, Inc; National Center for
Research Resources (NCRR) [025014-01]
FX We thank the ARCI families for their participation in the National
Registry of Ichthyosis and Related Disorders. We also thank the members
of the American Academy of Dermatology for their help in the recruitment
of ARCI families and the members of the Foundation of Ichthyosis and
Related Skin Types ( FIRST). SF is a fellow of the National Institutes
of Health (NIH) Clinical Research Training Program, a public-private
partnership supported jointly by the NIH and Pfizer, Inc ( via a grant
to the Foundation for NIH from Pfizer, Inc). SJB is president of GeneDx
(Gaithersburg, MD), and SF, M-HW, MH, SMS, DJL and JRT work for the US
government. 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 organisations
imply endorsement by the US government. This research was supported in
part by the Intramural Research Program of the NIH and FIRST. The
project described was also supported by a grant ( no 025014-01) from the
National Center for Research Resources (NCRR), a component of the NIH,
and the NIH Roadmap for Medical Research, and its contents are solely
the responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH. Information on NCRR is available at
http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical
Research Enterprise can be obtained from
http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.
NR 69
TC 27
Z9 30
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD FEB
PY 2009
VL 46
IS 2
BP 103
EP 111
DI 10.1136/jmg.2008.060905
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 402RQ
UT WOS:000263031200005
PM 18948357
ER
PT J
AU Zabow, G
Koretsky, AP
Moreland, J
AF Zabow, G.
Koretsky, A. P.
Moreland, J.
TI Design and fabrication of a micromachined multispectral magnetic
resonance imaging agent
SO JOURNAL OF MICROMECHANICS AND MICROENGINEERING
LA English
DT Article
ID IRON-OXIDE; NANOPARTICLES; NANOCRYSTALS; DEVICES; SENSITIVITY; MRI
AB This paper describes the fabrication details of magnetic nano- and microstructures that enable a new class of multispectral magnetic resonance imaging agents. Magnetic field and associated geometrical fabrication constraints particular to these new multispectral contrast agents are described, and fabrication schemes based on both electrochemical deposition and thermal evaporation are presented. Relative advantages and disadvantages of top-down microfabrication approaches versus traditional bottom-up chemical synthesis routes are discussed with a focus on trade-offs between resulting microparticle functionality and fabrication process economy. It is shown that large numbers of contrast agent nano- or microstructures can be simultaneously fabricated, suggesting that top-down microfabricated contrast agents may represent an economical, attractive alternative to those based on chemically synthesized molecules or nanoparticles.
C1 [Zabow, G.; Moreland, J.] Natl Inst Stand & Technol, Electromagnet Div, Boulder, CO USA.
[Zabow, G.; Koretsky, A. P.] NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Zabow, G (reprint author), Natl Inst Stand & Technol, Electromagnet Div, Boulder, CO USA.
EM zabow@boulder.nist.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIH NINDS Intramural Research Program; National Research Council
FX We thank Dr Stephen Dodd for helpful discussions, technical advice and
assistance. This work was supported in part by the NIH NINDS Intramural
Research Program. GZ also acknowledges support from a National Research
Council fellowship award.
NR 18
TC 8
Z9 8
U1 0
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0960-1317
J9 J MICROMECH MICROENG
JI J. Micromech. Microeng.
PD FEB
PY 2009
VL 19
IS 2
AR 025020
DI 10.1088/0960-1317/19/2/025020
PG 10
WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology;
Instruments & Instrumentation; Physics, Applied
SC Engineering; Science & Technology - Other Topics; Instruments &
Instrumentation; Physics
GA 399FR
UT WOS:000262786300021
ER
PT J
AU Murphy, E
Allen, DG
AF Murphy, Elizabeth
Allen, David G.
TI Why did the NHE inhibitor clinical trials fail?
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Editorial Material
ID NA+-H+ EXCHANGE; CARDIAC PURKINJE-FIBER; ISOLATED RAT-HEART;
MYOCARDIAL-INFARCTION; INTRACELLULAR NA+; VENTRICULAR MYOCYTES; EARLY
REPERFUSION; SODIUM CURRENT; ISCHEMIA; CARIPORIDE
C1 [Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
[Allen, David G.] Univ Sydney, Sch Med Sci & Bosch Inst F13, Sydney, NSW 2006, Australia.
RP Murphy, E (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 40
TC 25
Z9 25
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD FEB
PY 2009
VL 46
IS 2
BP 137
EP 141
DI 10.1016/j.yjmcc.2008.09.715
PG 5
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 398BY
UT WOS:000262707500004
PM 19027021
ER
PT J
AU Creson, TK
Yuan, PX
Manji, HK
Chen, G
AF Creson, Thomas K.
Yuan, Peixiong
Manji, Husseini K.
Chen, Guang
TI Evidence for Involvement of ERK, PI3K, and RSK in Induction of Bcl-2 by
Valproate
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE Valproate; bcl-2; ERK; PI3K; RSK
ID SIGNAL-REGULATED KINASE; NERVE GROWTH-FACTOR; GLYCOGEN-SYNTHASE
KINASE-3; MOOD STABILIZER; HISTONE DEACETYLASE; NEUROTROPHIC FACTOR;
PHOSPHATIDYLINOSITOL 3-KINASE; INOSITOL BIOSYNTHESIS; TRANSCRIPTION
FACTOR; PHOSPHORYLATED CREB
AB Valproate, an anticonvulsant and mood stabilizer, up-regulates Bcl-2, a neurotrophic/neuroprotective protein. In this study, we investigated the molecular mechanism through which Bcl-2 is up-regulated by valproate using cultured human neuron-like cells. Valproate, within therapeutically relevant ranges, induced time- and concentration-dependent up-regulations of both Bcl-2 messenger RNA and protein implicating an underlying gene transcriptional-mediated mechanism. Bcl-2 up-regulations were associated with ERK1/2 and PI3K pathway activations and elevated levels of activated phospho-RSK and phospho-CREB, convergent targets of the ERK1/2 and PI3K pathways. Valproate increased transcriptional activity of a human bcl-2 promoter-reporter gene construct. This effect was attenuated, but not blocked, by mutation of a CREB DNA binding site, a CRE site in the human bcl-2 promoter sequence. ERK and/or PI3K pathway inhibitors and RSK1 small hairpin RNA knockdown reduced, but did not abolish, baseline and valproate-induced promoter activities and lowered Bcl-2 protein levels. These data collectively suggest that valproate induces Bcl-2 regulation partially through activations of the ERK and PI3K cascades and their convergent kinase, RSK, although other unknown mechanism(s) are likely involved. Given the known roles of Bcl-2 in the central nervous system, the current findings offer a partial yet complex molecular mechanistic explanation for the known neurobiological effects of valproate including neurite growth, neuronal survival, and neurogenesis.
C1 [Creson, Thomas K.; Yuan, Peixiong; Manji, Husseini K.; Chen, Guang] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, G (reprint author), NIMH, Mol Pathophysiol Lab, NIH, 35 Convent Dr,Bldg 35,Rm 1C-912, Bethesda, MD 20892 USA.
EM guangchen@mail.nih.gov
RI Chen, Guang/A-2570-2017
FU NIMH intramural program; NARSAD research award
FX This work was supported by the NIMH intramural program (Manji and Chen)
and a NARSAD research award (Chen).
NR 51
TC 44
Z9 44
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD FEB
PY 2009
VL 37
IS 2
BP 123
EP 134
DI 10.1007/s12031-008-9122-2
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 387SG
UT WOS:000261971300003
PM 18677583
ER
PT J
AU Park, J
Koshimizu, H
Loh, Y
AF Park, Joshua J.
Koshimizu, Hisatsugu
Loh, Y. Peng
TI Biogenesis and Transport of Secretory Granules to Release Site in
Neuroendocrine Cells
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE Biogenesis of peptidergic secretory granules; Chromogranin A; Expression
of inhibitor of protein Nexin-1; Carboxypeptidase E or cytoplasmic tail;
Post-Golgi transport; Dynactin; Microtubule-based motors
ID TRANSCRIPTIONAL REPRESSOR REST; TYROSINE-HYDROXYLASE GENE;
CHROMOGRANIN-A; CARBOXYPEPTIDASE-E; PC12 CELLS; BETA-CELLS; CYTOPLASMIC
DYNEIN; TARGETED ABLATION; PROTEIN; EXPRESSION
AB Biogenesis and post-Golgi transport of peptidergic secretory granules to the release site are crucial for secretion of neuropeptides from neuroendocrine cells. Recent studies have uncovered multilevel molecular mechanisms for the regulation of secretory granule biogenesis. Insulinoma-associated protein 2 (ICA512/IA-2), polypyrimidine-tract binding protein, and chromogranin A have been identified to regulate secretory granule biogenesis at the transcriptional, posttranscriptional, and posttranslational levels, respectively, by increasing granule protein levels, which in turn drives granule formation after stimulation. Post-Golgi transport of secretory granules is microtubule-based and mediated by transmembrane carboxypeptidase E (CPE). The cytoplasmic tail of CPE anchors secretory granules to the microtubule motors, kinesin-2 and -3, or dynein, via interaction with the adaptor, dynactin, to mediate anterograde and retrograde transport, respectively.
C1 [Park, Joshua J.; Koshimizu, Hisatsugu; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Program, NIH, Bethesda, MD 20892 USA.
RP Loh, Y (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Program, NIH, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
RI Koshimizu, Hisatsugu/G-5536-2010
FU National Institute of Child Health and Human Development; National
Institutes of Health
FX This research is supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 49
TC 17
Z9 18
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD FEB
PY 2009
VL 37
IS 2
BP 151
EP 159
DI 10.1007/s12031-008-9098-y
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 387SG
UT WOS:000261971300006
PM 18607778
ER
PT J
AU Wu, MX
Yu, KF
Liu, AY
AF Wu, Mi-Xia
Yu, Kai F.
Liu, Aiyi
TI Exact inference on contrasts in means of intraclass correlation models
with missing responses
SO JOURNAL OF MULTIVARIATE ANALYSIS
LA English
DT Article
DE Contrast; Exact test; Intraclass correlation model; Linear mixed model;
Simultaneous confidence intervals
ID CONFIDENCE-INTERVALS
AB Intraclass correlation models with missing data at random are considered. With a properly reduced model, a general method, which allows repeated observations with missing data in a non-monotone pattern, is proposed to construct exact test statistics and simultaneous confidence intervals for linear contrasts in the means. Simulation results are given to compare exact and asymptotic simultaneous confidence intervals. A real example is provided for the illustration of the proposed method. Published by Elsevier Inc.
C1 [Wu, Mi-Xia; Yu, Kai F.; Liu, Aiyi] NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Rockville, MD 20852 USA.
[Wu, Mi-Xia] Beijing Univ Technol, Coll Appl Sci, Beijing 100022, Peoples R China.
RP Wu, MX (reprint author), NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM wumixia@gmail.com
OI Liu, Aiyi/0000-0002-6618-5082
FU Intramural NIH HHS [Z01 HD002535-09]
NR 10
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0047-259X
J9 J MULTIVARIATE ANAL
JI J. Multivar. Anal.
PD FEB
PY 2009
VL 100
IS 2
BP 301
EP 308
DI 10.1016/j.jmva.2008.05.002
PG 8
WC Statistics & Probability
SC Mathematics
GA 382BN
UT WOS:000261580000005
PM 20126283
ER
PT J
AU Fitch, RW
Sturgeon, GD
Patel, SR
Spande, TF
Garraffo, HM
Daly, JW
Blaauw, RH
AF Fitch, Richard W.
Sturgeon, Gordon D.
Patel, Shaun R.
Spande, Thomas F.
Garraffo, H. Martin
Daly, John W.
Blaauw, Richard H.
TI Epiquinamide: A Poison That Wasn't from a Frog That Was
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID INDOLIZIDINE ALKALOIDS; RAY-ANALYSIS; (+)-EPIQUINAMIDE; DENDROBATIDAE;
TRICOLOR; 223G
AB In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide (1), a novel alkaloid isolated from an Ecuadoran poison frog, Epipedobates tricolor. Since then, several groups, including ours, have undertaken synthetic efforts to produce this compound, which appeared initially to be a novel, beta 2-selective nicotinic acetylcholine receptor agonist. Based on prior chiral GC analysis of synthetic and natural samples, the absolute structure of this alkaloid was established as (1S,9aS)-1-acetamidoquinolizidine. We have synthesized the (1R*,9aS*)-isomer (epi-epiquinamide) using an iminium ion nitroaldol reaction as the key step. We have also synthesized ent-1 semisynthetically from (-)-lupinine. Synthetic epiquinamide is inactive at nicotinic receptors, in accord with recently published reports. We have determined that the activity initially reported is due to cross-contamination from co-occurring epibatidine in the isolated material.
C1 [Fitch, Richard W.; Sturgeon, Gordon D.] Indiana State Univ, Dept Chem, Terre Haute, IN 47809 USA.
[Patel, Shaun R.] Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA.
[Spande, Thomas F.; Garraffo, H. Martin; Daly, John W.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Blaauw, Richard H.] Chiralix BV, NL-6503 CB Nijmegen, Netherlands.
RP Fitch, RW (reprint author), Indiana State Univ, Dept Chem, 600 Chestnut St,Sci S35E, Terre Haute, IN 47809 USA.
EM rfitch@indstate.edu
FU Department of Chemistry and College of Arts and Sciences at Indiana
State University [12030168]; Indiana State University Promising Scholar
Award; National Science Foundation [CHE0521075]; NIDDK
FX K. J. Lipscomb and R. J. Tucker are acknowledged for performing
exploratory experiments. A generous gift of HEK cells expressing various
subunit combinations for nicotinic receptors by Drs. K. J. Kellar and Y.
Xiao of Georgetown University Medical School is gratefully acknowledged.
This work was performed with funds from the Department of Chemistry and
College of Arts and Sciences at Indiana State University (startup
funding to R.W.F. and summer stipend to G.D.S.), as well as a Sigma Xi
Grant-in-aid (12030168 to K.J.L.), the Lilly Endowment (Wabash College
Indiana Internship Initiative summer stipend to S.R.P. and Indiana State
University Promising Scholar Award to R.W.F.), and the National Science
Foundation (CHE0521075 for a 400 MHz NMR spectrometer at Indiana State
University). Work performed at NIH was supported by the intramural
program of NIDDK.
NR 32
TC 27
Z9 27
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD FEB
PY 2009
VL 72
IS 2
BP 243
EP 247
DI 10.1021/np8005452
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 413BR
UT WOS:000263768400011
PM 19245264
ER
PT J
AU Benninger, DH
Thees, S
Kollias, SS
Bassetti, CL
Waldvogel, D
AF Benninger, David H.
Thees, Sebastian
Kollias, Spyros S.
Bassetti, Claudio L.
Waldvogel, Daniel
TI Morphological differences in Parkinson's disease with and without rest
tremor
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Parkinson's disease; voxel-based morphometry; tremor akinetic-rigid
syndrome
ID MULTIPLE SYSTEM ATROPHY; THALAMIC-STIMULATION; LONG-TERM; MOTOR CORTEX;
PEDUNCULOPONTINE NUCLEUS; DEPRESSION INVENTORY; MOVEMENT-DISORDERS;
PROGNOSTIC FACTORS; METABOLIC ANATOMY; CEREBRAL ATROPHY
AB Rest tremor is a hallmark of Parkinson's disease (PD), but its pathogenesis remains incompletely understood. Nigro-striatal dopamine deficiency correlates best with bradykinesia, but not with tremor. Oscillating neurons in one or multiple localizations within the basal gangliathalamo-cortical loop may cause rest tremor, and an active contribution of the cerebellum and the cerebello-thalamo-cortical projections has been postulated.
To compare the pattern of grey matter volume in PD patients with and without tremor to identify structural correlates of rest tremor.
Voxel-based morphometry (VBM) of a high-resolution 3 Tesla, T1-weighted MR images, pre-processed according to an optimized protocol using SPM2, was performed in 24 patients with mild to moderate PD comparing local grey matter volume in patients with (n = 14) and without rest tremor (n = 10).
Grey matter volume is decreased in the right quadrangular lobe and declive of the cerebellum in PD with tremor compared to those without (PFDR < 0.05).
These results demonstrate for the first time morphological changes in the cerebellum in PD patients with rest tremor and highlight the involvement of the cerebellum and cerebello- thalamo-cortical circuit in the pathogenesis of parkinsonian rest tremor.
C1 [Benninger, David H.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Benninger, David H.; Bassetti, Claudio L.; Waldvogel, Daniel] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Thees, Sebastian; Kollias, Spyros S.] Univ Zurich Hosp, Dept Neuroradiol, CH-8091 Zurich, Switzerland.
RP Benninger, DH (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N240 MSC1428,Ctr Dr, Bethesda, MD 20892 USA.
EM benningerd@ninds.nih.gov
RI Kollias, Spyros/J-9276-2012; Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
NR 67
TC 46
Z9 50
U1 1
U2 4
PU DR DIETRICH STEINKOPFF VERLAG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD FEB
PY 2009
VL 256
IS 2
BP 256
EP 263
DI 10.1007/s00415-009-0092-2
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 418VE
UT WOS:000264176700014
PM 19219572
ER
PT J
AU Foltynie, T
Cheeran, B
Williams-Gray, CH
Edwards, MJ
Schneider, SA
Weinberger, D
Rothwell, JC
Barker, RA
Bhatia, KP
AF Foltynie, T.
Cheeran, B.
Williams-Gray, C. H.
Edwards, M. J.
Schneider, S. A.
Weinberger, D.
Rothwell, J. C.
Barker, R. A.
Bhatia, K. P.
TI BDNF val66met influences time to onset of levodopa induced dyskinesia in
Parkinson's disease
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID ACTIVITY-DEPENDENT SECRETION; AGE-OF-ONSET; NEUROTROPHIC FACTOR; L-DOPA;
MOTOR COMPLICATIONS; SYNAPTIC PLASTICITY; BRAIN; POLYMORPHISM;
EXPRESSION; ASSOCIATION
AB Background: Levodopa induced dyskinesias (LID) are a common problem which ultimately limit the effective treatment of patients with Parkinson's disease (PD). There is accumulating evidence that LID develop due to abnormal synaptic plasticity, which is in turn influenced by the release of brain derived neurotrophic factor (BDNF).
Methods: The influence of a common functional polymorphism of the BDNF gene on the risk of developing dyskinesias in a large cohort of patients with PD (n = 315), who were independently and variably treated with levodopa and/or other dopaminergic treatments, was investigated.
Results: Patients with the met allele of BDNF, associated with lower activity dependent secretion of BDNF, were at significantly higher risk of developing dyskinesias earlier in the course of treatment with dopaminergic agents (hazard ratio for each additional met allele 2.12, p = 0.001), which persisted following adjustment for potential confounding variables.
Conclusion: This functional polymorphism may help predict which individuals are most at risk of LID and is consistent with the known actions of BDNF on synaptic plasticity in the striatum.
C1 [Foltynie, T.; Cheeran, B.; Edwards, M. J.; Schneider, S. A.; Rothwell, J. C.; Bhatia, K. P.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Foltynie, T.; Williams-Gray, C. H.] Cambridge Ctr Brian Repair, Cambridge, England.
[Weinberger, D.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
RP Foltynie, T (reprint author), UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Queen Sq, London WC1N 3BG, England.
EM T.Foltynie@ion.ucl.ac.uk
RI Edwards, Mark/F-1052-2012;
OI Rothwell, John/0000-0003-1367-6467; Cheeran, Binith/0000-0002-3442-1044
FU Wellcome Trust
FX The Wellcome Trust provided financial support to TF through a Clinical
Training Fellowship during the collection of the data used in this
study.
NR 36
TC 60
Z9 63
U1 1
U2 6
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD FEB
PY 2009
VL 80
IS 2
BP 141
EP 144
DI 10.1136/jnnp.2008.154294
PG 4
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 396HH
UT WOS:000262582300007
PM 18977816
ER
PT J
AU Micsenyi, MC
Dobrenis, K
Stephney, G
Pickel, J
Vanier, MT
Slaugenhaupt, SA
Walkley, SU
AF Micsenyi, Matthew C.
Dobrenis, Kostantin
Stephney, Gloria
Pickel, James
Vanier, Marie T.
Slaugenhaupt, Susan A.
Walkley, Steven U.
TI Neuropathology of the Mcoln1(-/-) Knockout Mouse Model of Mucolipidosis
Type IV
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Axonal spheroids; Bis(monoacylglycero) phosphate; Gangliosides;
Lysosomal disease; Mucolipin 1; P62/Sequestosome 1
ID NEURONAL-CEROID-LIPOFUSCINOSIS; LYSOSOMAL STORAGE DISORDERS;
LYSOBISPHOSPHATIDIC ACID; CULTURED FIBROBLASTS; CATION CHANNEL; DISEASE;
AUTOPHAGY; ACCUMULATION; P62/SQSTM1; GENE
AB The recently developed Mcoln1(-/-) knockout mouse provides a novel model for analyzing mucolipin 1 function and mucolipidosis type IV disease. Here we characterize the neuropathology of Mcoln1(-/-) mouse at the end stage. Evidence of ganglioside accumulation, including increases in GM2, GM3, and GD3 and redistribution of GM1, was found throughout the central nervous system (CNS) independent of significant cholesterol accumulation. Unexpectedly, colocalization studies using immunofluorescence confocal microscopy revealed that GM1 and GM2 were present in separate vesicles within individual neurons. While GM2 was significantly colocalized with LAMP2, consistent with late-endosomal/lysosomal processing, some GIM2-immunoreactivity occurred in LAMP2-negative sites, suggesting involvement of other vesicular systems. P62/Sequestosome 1 (P62/SQSTM1) inclusions were also identified in the CNS of the Mcoln1(-/-) mouse, Suggesting deficiencies in protein degradation. Glial cell activation was increased in brain, and there was evidence of reduced myelination in cerebral and cerebellar white matter tracts. Autofluorescent material accumulated throughout the brains of the knockout mice. Finally, axonal spheroids were prevalent in white matter tracts and Purkinje cell axons. This neuropathological characterization of the Mcoln1(-/-) mouse provides an important step in understanding how mucolipin I loss of function affects the CNS and contributes to mucolipidosis type IV disease.
C1 [Micsenyi, Matthew C.; Dobrenis, Kostantin; Walkley, Steven U.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose Kennedy Ctr Res Mental Retardat & Human Dev, Bronx, NY 10461 USA.
[Pickel, James] NIMH, NIH, Bethesda, MD 20892 USA.
[Vanier, Marie T.] Laennec Med Sch, INSERM, Lyon, France.
[Vanier, Marie T.] Lyon Univ, Lyon, France.
[Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Walkley, SU (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose Kennedy Ctr Res Mental Retardat & Human Dev, 1410 Pelham Pkwy S,Room 618, Bronx, NY 10461 USA.
EM walkley@accom.yu.edu
FU NICHD NIH HHS [P30 HD001799, R01 HD045561]; NINDS NIH HHS [R01 NS039995,
R01 NS39995]
NR 48
TC 38
Z9 39
U1 0
U2 1
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 FEB
PY 2009
VL 68
IS 2
BP 125
EP 135
PG 11
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 402KN
UT WOS:000263012700002
PM 19151629
ER
PT J
AU Gonzalez-Islas, C
Chub, N
Wenner, P
AF Gonzalez-Islas, Carlos
Chub, Nikolai
Wenner, Peter
TI NKCC1 and AE3 Appear to Accumulate Chloride in Embryonic Motoneurons
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID SPONTANEOUS NETWORK ACTIVITY; SPONTANEOUS RHYTHMIC ACTIVITY; RAT
NEOCORTICAL NEURONS; CHICK SPINAL-CORD; INTRACELLULAR CHLORIDE; RETINAL
NEURONS; LUMBAR MOTONEURONS; NERVOUS-SYSTEM; IONIC BASIS; COTRANSPORTER
AB Gonzalez-Islas C, Chub N, Wenner P. NKCC1 and AE3 appear to accumulate chloride in embryonic motoneurons. J Neurophysiol 101: 507-518, 2009. First published November 26, 2008; doi: 10.1152/jn.90986.2008. During early development, gamma-aminobutyric acid (GABA) depolarizes and excites neurons, contrary to its typical function in the mature nervous system. As a result, developing networks are hyperexcitable and experience a spontaneous network activity that is important for several aspects of development. GABA is depolarizing because chloride is accumulated beyond its passive distribution in these developing cells. Identifying all of the transporters that accumulate chloride in immature neurons has been elusive and it is unknown whether chloride levels are different at synaptic and extrasynaptic locations. We have therefore assessed intracellular chloride levels specifically at synaptic locations in embryonic motoneurons by measuring the GABAergic reversal potential (E-GABA) for GABA(A) miniature postsynaptic currents. When whole cell patch solutions contained 17-52 mM chloride, we found that synaptic E GABA was around -30 mV. Because of the low HCO3- permeability of the GABA(A) receptor, this value of E-GABA corresponds to approximately 50 mM intracellular chloride. It is likely that synaptic chloride is maintained at levels higher than the patch solution by chloride accumulators. We show that the Na+-K+-2Cl (-) cotransporter, NKCC1, is clearly involved in the accumulation of chloride in motoneurons because blocking this transporter hyperpolarized E-GABA and reduced nerve potentials evoked by local application of a GABA(A) agonist. However, chloride accumulation following NKCC1 block was still clearly present. We find physiological evidence of chloride accumulation that is dependent on HCO3- and sensitive to an anion exchanger blocker. These results suggest that the anion exchanger, AE3, is also likely to contribute to chloride accumulation in embryonic motoneurons.
C1 [Gonzalez-Islas, Carlos; Wenner, Peter] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
[Chub, Nikolai] NINDS, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Wenner, P (reprint author), Emory Univ, Sch Med, Dept Physiol, Room 601,Whitehead Bldg, Atlanta, GA 30322 USA.
EM pwenner@emory.edu
OI Wenner, Peter/0000-0002-7072-2194
FU National Institute of Neurological Disorders and Stroke (NINDS)
[NS-046510]; National Science Foundation [0616097]
FX This research was supported by National Institute of Neurological
Disorders and Stroke (NINDS) Grant NS-046510 and National Science
Foundation Grant 0616097 to P. Wenner and by the intramural program of
the NINDS.
NR 47
TC 47
Z9 47
U1 1
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB
PY 2009
VL 101
IS 2
BP 507
EP 518
DI 10.1152/jn.90986.2008
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 403ZK
UT WOS:000263120300002
PM 19036864
ER
PT J
AU Bell, AH
Hadj-Bouziane, F
Frihauf, JB
Tootell, RBH
Ungerleider, LG
AF Bell, Andrew H.
Hadj-Bouziane, Fadila
Frihauf, Jennifer B.
Tootell, Roger B. H.
Ungerleider, Leslie G.
TI Object Representations in the Temporal Cortex of Monkeys and Humans as
Revealed by Functional Magnetic Resonance Imaging
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID POSTERIOR INFEROTEMPORAL CORTEX; HUMAN EXTRASTRIATE CORTEX; MACAQUE
CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; MIDDLE FUSIFORM GYRUS; FACE
PERCEPTION; TOPOGRAPHICAL DISORIENTATION; ACQUIRED PROSOPAGNOSIA;
RESPONSE PATTERNS; INDIVIDUAL FACES
AB Bell AH, Hadj-Bouziane F, Frihauf JB, Tootell RB, Ungerleider LG. Object representations in the temporal cortex of monkeys and humans as revealed by functional magnetic resonance imaging. J Neurophysiol 101: 688-700, 2009. First published December 3, 2008; doi:10.1152/jn.90657.2008. Increasing evidence suggests that the neural processes associated with identifying everyday stimuli include the classification of those stimuli into a limited number of semantic categories. How the neural representations of these stimuli are organized in the temporal lobe remains under debate. Here we used functional magnetic resonance imaging (fMRI) to identify correlates for three current hypotheses concerning object representations in the inferior temporal (IT) cortex of monkeys and humans: representations based on animacy, semantic categories, or visual features. Subjects were presented with blocked images of faces, body parts (animate stimuli), objects, and places (inanimate stimuli), and multiple overlapping contrasts were used to identify the voxels most selective for each category. Stimulus representations appeared to segregate according to semantic relationships. Discrete regions selective for animate and inanimate stimuli were found in both species. These regions could be further subdivided into regions selective for individual categories. Notably, face-selective regions were contiguous with body-part-selective regions, and object-selective regions were contiguous with placeselective regions. When category-selective regions in monkeys were tested with blocks of single exemplars, individual voxels showed preferences for visually dissimilar exemplars from the same category and voxels with similar preferences tended to cluster together. Our results provide some novel observations with respect to how stimulus representations are organized in IT cortex. In addition, they further support the idea that representations of complex stimuli in IT cortex are organized into multiple hierarchical tiers, encompassing both semantic and physical properties.
C1 [Bell, Andrew H.; Hadj-Bouziane, Fadila; Frihauf, Jennifer B.; Tootell, Roger B. H.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Bell, AH (reprint author), NIMH, Lab Brain & Cognit, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM bellah@mail.nih.gov
RI Hadj-Bouziane, Fadila/A-1180-2013;
OI Bell, Andrew/0000-0001-8420-4622
FU National Institutes of Health [R01MH-67529, R01 EY-017081]
FX This work was supported by grants from the National Institutes of Health
(R01MH-67529 and R01 EY-017081 to R. B. H. Tootell, the Athinoula A.
Martinos Center for Biomedical Imaging, the National Center for Research
Resources, and the National Institute of Mental Health Intramural
Research Program to A. H. Bell, F. Hadj-Bouziane, J. B. Frihauf, and L.
G. Ungerleider.
NR 88
TC 90
Z9 91
U1 1
U2 10
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB
PY 2009
VL 101
IS 2
BP 688
EP 700
DI 10.1152/jn.90657.2008
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 403ZK
UT WOS:000263120300018
PM 19052111
ER
PT J
AU Bredfeldt, CE
Read, JCA
Cumming, BG
AF Bredfeldt, C. E.
Read, J. C. A.
Cumming, B. G.
TI A Quantitative Explanation of Responses to Disparity-Defined Edges in
Macaque V2
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID MONKEY VISUAL-CORTEX; RECEPTIVE-FIELD SIZE; AREA V2; V1 NEURONS; NEURAL
MECHANISMS; BORDER OWNERSHIP; SIMPLE CELLS; SELECTIVITY; REPRESENTATION;
ORGANIZATION
AB Bredfeldt CE, Read JCA, Cumming BG. A quantitative explanation of responses to disparity-defined edges in macaque V2. J Neurophysiol 101: 701-713, 2009. First published December 10, 2008; doi:10.1152/jn.00729.2007. Previous experiments have shown that V2 neurons respond to complex stimuli such as cyclopean edges (edges defined purely by binocular disparity), angles, and motion borders. It is currently unknown whether these responses are a simple consequence of converging inputs from a prior stage of processing (V1). Alternatively, they may identify edges in a way that is invariant across a range of visual cues defining the edge, in which case they could provide a neuronal substrate for scene segmentation. Here, we examine the ability of a simple feedforward model that combines two V1-like inputs to describe the responses of V2 neurons to cyclopean edges. A linear feedforward model was able to qualitatively reproduce the major patterns of response enhancement for cyclopean edges seen in V2. However, quantitative fitting revealed that this model usually predicts response suppression by some edge configurations and such suppression was rarely seen in the data. This problem was resolved by introducing a squaring nonlinearity at the output of the individual inputs prior to combination. The extended model produced extremely good fits to most of our data. We conclude that the responses of V2 neurons to complex stimuli such as cyclopean edges can be adequately explained by a simple convergence model and do not necessarily represent the development of sophisticated mechanisms that signal scene segmentation, although they probably constitute a step toward this goal.
C1 [Bredfeldt, C. E.; Cumming, B. G.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Read, J. C. A.] Univ Newcastle, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
RP Cumming, BG (reprint author), 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM bgc@nei.nih.gov
RI Read, Jenny/A-7493-2013
OI Read, Jenny/0000-0002-9029-5185
FU National Institutes of Health, National Eye Institute; Royal Society
University Research Fellowship [UF041260]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Eye Institute, and by Royal
Society University Research Fellowship Grant UF041260 awarded to J. C.
A. Read.
NR 28
TC 5
Z9 6
U1 1
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB
PY 2009
VL 101
IS 2
BP 701
EP 713
DI 10.1152/jn.00729.2007
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 403ZK
UT WOS:000263120300019
PM 19073795
ER
PT J
AU Bouret, S
Richmond, BJ
AF Bouret, Sebastien
Richmond, Barry J.
TI Relation of Locus Coeruleus Neurons in Monkeys to Pavlovian and Operant
Behaviors
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID REWARD SCHEDULES; PHASIC ACTIVATION; CERULEUS NEURONS; VENTRAL STRIATUM;
CENTRAL NUCLEUS; CORTEX; NOREPINEPHRINE; RETRIEVAL; ATTENTION; RESPONSES
AB Bouret S, Richmond BJ. Relation of locus coeruleus neurons in monkeys to Pavlovian and operant behaviors. J Neurophysiol 101: 898-911, 2009. First published December 17, 2008; doi: 10.1152/jn.91048.2008. Noradrenaline is released throughout the forebrain from locus coeruleus (LC) projections in close temporal proximity to emotional and goal-directed events. To examine interactive influences of these processes on LC neuronal activity, we used a task where Pavlovian and operant processes vary and can be easily identified. We recorded 69 single LC neurons from two monkeys performing a task where cues indicate the progression through schedules of one, two, or three operant trials. Pavlovian responses and phasic LC activations occur following the appearance of conditioned visual cues (54/69 neurons), especially those at the beginning of new schedules, whether the current trial will be rewarded (single trial schedule) or not (2 or 3 trial schedules), and after visual imperative signals eliciting the operant response (64/69 neurons), whether the current trial will be rewarded or not. The modulation of LC responses seems to be relatively independent of attention or motivation, because the responses do not covary with operant performance in the task. The magnitude of LC responses across the schedules varied in close relation to the intensity of Pavlovian behavior but these responses were also modulated by operant processes. Our conclusion is that LC activation occurs when task-relevant stimuli evoke a conditioned instinctive (Pavlovian) response, with the strength of the activation also being modulated by goal-directed processes. Thus locus coeruleus neurons broadcast information about stimulus-elicited primitive and goal-directed behaviors to forebrain structures important for executive functions and emotions.
C1 [Bouret, Sebastien; Richmond, Barry J.] NIMH, Neuropsychol Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA.
EM bjr@ln.nimh.nih.gov
RI Bouret, Sebastien/J-9383-2013
OI Bouret, Sebastien/0000-0003-2279-6161
FU Intramural Research Program of the National Institute of Mental Health;
Fondation Fyssen
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health. S. Bouret was partially supported
by the Fondation Fyssen.
NR 35
TC 26
Z9 26
U1 1
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB
PY 2009
VL 101
IS 2
BP 898
EP 911
DI 10.1152/jn.91048.2008
PG 14
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 403ZK
UT WOS:000263120300036
PM 19091919
ER
PT J
AU Shen, H
Luo, Y
Kuo, CC
Deng, XL
Chang, CF
Harvey, BK
Hoffer, BJ
Wang, Y
AF Shen, Hui
Luo, Yu
Kuo, Chi-Chung
Deng, Xiaolin
Chang, Chen-Fu
Harvey, Brandon K.
Hoffer, Barry J.
Wang, Yun
TI 9-Cis-Retinoic Acid Reduces Ischemic Brain Injury in Rodents Via Bone
Morphogenetic Protein
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE retinoic acid; BMP7; stroke; neuroprotection
ID MIDDLE CEREBRAL-ARTERY; RETINOID-X-RECEPTOR; NEURAL DIFFERENTIATION;
DOCOSAHEXAENOIC ACID; OSTEOGENIC PROTEIN-1; INDUCED APOPTOSIS; BMP-7
EXPRESSION; NUCLEAR RECEPTOR; OXIDATIVE STRESS; STROKE RATS
AB Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H(2)O(2) or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia-induced injury, and these effects involve BMPs. (c) 2008 Wiley-Liss, Inc.
C1 [Wang, Yun] Natl Inst Drug Abuse, Intramural Res Program, Neural Protect & Regenerat Sect, Baltimore, MD 21224 USA.
RP Wang, Y (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Neural Protect & Regenerat Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM ywang@intra.nida.nih.gov
RI Harvey, Brandon/A-5559-2010; luo, Yu (Agnes)/E-4446-2010
FU IRP of NIDA, NIH, DHHS
FX Contract grant sponsor: IRP of NIDA, NIH, DHHS.
NR 43
TC 20
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 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD FEB 1
PY 2009
VL 87
IS 2
BP 545
EP 555
DI 10.1002/jnr.21865
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 403JQ
UT WOS:000263079300025
PM 18803283
ER
PT J
AU Lonser, RR
Butman, JA
Kiringoda, R
Song, D
Oldfield, EH
AF Lonser, Russell R.
Butman, John A.
Kiringoda, Ruwan
Song, Debbie
Oldfield, Edward H.
TI Pituitary stalk hemangioblastomas in von Hippel-Lindau disease
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE hemangioblastoma; pituitary stalk; treatment options; tumor incidence;
von Hippel-Lindau disease
ID CENTRAL-NERVOUS-SYSTEM; MORBID HEARING-LOSS; OF-THE-LITERATURE;
SUPRASELLAR HEMANGIOBLASTOMA; ENDOLYMPHATIC SAC; INTRASELLAR
HEMANGIOBLASTOMA; NATURAL-HISTORY; TUMORS; RADIOSURGERY; RESECTION
AB Object. Pituitary stalk hemangioblastomas are rare. and information on them is limited to a small number of case reports. To gain insight into the incidence, clinical effects, and management of pituitary stalk hemangioblastomas, the authors analyzed a series of patients with von Hippel-Lindau (VHL) disease.
Methods. Patients with VHL disease who were enrolled in a prospective National Institutes of Health natural history study were included. Clinical, imaging, and laboratory findings were analyzed.
Results. Two hundred fifty patients were included in the study (120 male and 130 female patients). In 8 patients (3%) 8 pituitary stalk hemangioblastomas were identified on MR imaging. This anatomical location was the most common supratentorial site for these lesions; 29% of all supratentorial hemangioblastomas were found there. The mean (+/- standard deviation) pituitary stalk hemangioblastoma volume was 0.5 +/- 0.9 cm(3) (range 0.08-2.8 cm(3)). Results. of endocrine laboratory profiles were normal in all patients. All patients remained asymptomatic and none required treatment during the follow-up period (mean duration 41.4 +/- 14.4 months).
Conclusions. The pituitary stalk is the most common site for the development of supratentorial hemangioblastomas in patients with VHL disease. Pituitary stalk hemangioblastomas often remain asymptomatic and do not require treatment. These findings indicate that pituitary stalk hemangioblastomas in patients with VHL disease may be managed with observation and that surgery for them can be reserved until associated signs or symptoms occur. (DOI: 10.3171/2008.4.17532)
C1 [Lonser, Russell R.; Kiringoda, Ruwan; Song, Debbie; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Butman, John A.] Ctr Clin, Neuroradiol Sect, Dept Diagnost Radiol, NIH, Bethesda, MD USA.
RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
RI Butman, John/A-2694-2008; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke at the NIH
FX The Intramural Research Program of the National Institute of
Neurological Disorders and Stroke at the NIH supported this research.
NR 25
TC 16
Z9 17
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD FEB
PY 2009
VL 110
IS 2
BP 350
EP 353
DI 10.3171/2008.4.17532
PG 4
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 399GI
UT WOS:000262788000021
PM 18834262
ER
PT J
AU Budde, MD
Frank, JA
AF Budde, Matthew D.
Frank, Joseph A.
TI Magnetic Tagging of Therapeutic Cells for MRI
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE molecular imaging; MRI; magnetic cellular tagging; immune cells; stem
cells
ID MESENCHYMAL STEM-CELLS; IN-VIVO MRI; RESONANCE TRACKING; CELLULAR
THERAPY; CONTRAST AGENT; NANOPARTICLES; REPORTER; MODEL; EXPRESSION;
REJECTION
AB Transplantation of stem cells or immune cells has shown promise for the treatment of several diseases. Monitoring magnetically la beled cells with MRI has furthered our understanding of cellular migration and the pathophysiology of diseases in experimental models. These studies should pave the way for guiding clinical trials using cell-based therapies. This review briefly describes the various methods used to label and track cells with MRI and the potential for such methods to translate to human applications.
C1 [Budde, Matthew D.; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Budde, MD (reprint author), NIH, Ctr Clin, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA.
EM buddem@cc.nih.gov
FU Intramural Research Program of the Clinical Center at the National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Clinical Center at the National Institutes of Health.
NR 33
TC 49
Z9 52
U1 1
U2 4
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 FEB
PY 2009
VL 50
IS 2
BP 171
EP 174
DI 10.2967/jnumed.108.053546
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 409EA
UT WOS:000263487800018
PM 19164242
ER
PT J
AU Crosier, MD
Booth, SL
Peter, I
Dawson-Hughes, B
Price, PA
O'Donnell, CJ
Hoffmann, U
Williamson, MK
Ordovas, JM
AF Crosier, Michael D.
Booth, Sarah L.
Peter, Inga
Dawson-Hughes, Bess
Price, Paul A.
O'Donnell, Christopher J.
Hoffmann, Udo
Williamson, Matthew K.
Ordovas, Jose M.
TI Matrix Gla Protein Polymorphisms are Associated with Coronary Artery
Calcification in Men
SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY
LA English
DT Article
DE matrix gla protein; coronary artery calcification; polymorphism; vitamin
K; atherosclerosis
ID COMPUTED-TOMOGRAPHY; RISK-FACTORS; ATHEROSCLEROSIS; DISEASE; SERUM;
GENE; RAT
AB Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent. (n=386; 60 to 80 3, of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802, rs1800801. or rs4236 (minor allele frequency: 21, 38, and 40%. respectively) were associated with a decreased quantity of CAC. relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations.
C1 [Crosier, Michael D.; Booth, Sarah L.; Dawson-Hughes, Bess; Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA.
[Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Price, Paul A.; Williamson, Matthew K.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiovasc CT Core Lab, Boston, MA 02114 USA.
RP Booth, SL (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, USDA, 711 Washington St, Boston, MA 02111 USA.
EM sarah.booth@tufts.edu
OI Ordovas, Jose/0000-0002-7581-5680
FU U.S. Department of Agriculture, Agricultural Research Service under
Cooperative Agreement [58-1950-7-707]; National Institute of Aging
[AG14759, HL69272, NIDDK T32DK62032]
FX Based upon work supported by the U.S. Department of Agriculture,
Agricultural Research Service under Cooperative Agreement No.
58-1950-7-707, National Institute of Aging (AG14759, HL69272 and NIDDK
T32DK62032). Any opinions. findings, conclusions or recommendations
expressed in this publication are those of the authors, and do not
necessarily reflect the view of the U.S. Department of Agriculture.
NR 27
TC 28
Z9 31
U1 0
U2 0
PU CENTER ACADEMIC PUBL JAPAN
PI TOKYO
PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN
SN 0301-4800
J9 J NUTR SCI VITAMINOL
JI J. Nutr. Sci. Vitaminol.
PD FEB
PY 2009
VL 55
IS 1
BP 59
EP 65
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 413BF
UT WOS:000263767200008
PM 19352064
ER
PT J
AU Capitini, CM
Derdak, J
Hughes, MS
Love, CP
Baird, K
Mackall, CL
Fry, TJ
AF Capitini, Christian M.
Derdak, Joanne
Hughes, Marybeth S.
Love, Cynthia P.
Baird, Kristin
Mackall, Crystal L.
Fry, Terry J.
TI Unusual Sites of Extraskeletal Metastases of Ewing Sarcoma After
Allogeneic Hematopoietic Stem Cell Transplantation
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE Ewing sarcoma; allogeneic stem cell transplant; metastasis
ID TUMORS; BRAIN
AB Allogeneic stein cell transplantation (SCT) for solid tumors remains under investigation. We report a case of extended disease stability after a nonmyeloablative peripheral blood SCT for metastatic, refractory Ewing sarcoma. Of note, the patient developed metastatic disease to 2 unusual sites-the brain and small intestine. The allogeneic SCT environment may alter typical metastatic patterns, and may represent an ideal platform to manipulate and enhance the antitumor immune response. Further clinical trials are needed to evaluate the role for allogeneic SCT for this disease.
C1 [Capitini, Christian M.; Derdak, Joanne; Love, Cynthia P.; Baird, Kristin; Mackall, Crystal L.; Fry, Terry J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Hughes, Marybeth S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Fry, Terry J.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
RP Capitini, CM (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Room 1W-5832, Bethesda, MD 20892 USA.
EM capitinic@mail.nih.gov
OI Capitini, Christian/0000-0002-2276-6731
FU Intramural NIH HHS [Z99 CA999999]
NR 15
TC 6
Z9 7
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD FEB
PY 2009
VL 31
IS 2
BP 142
EP 144
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 404FA
UT WOS:000263135100015
PM 19194203
ER
PT J
AU Maran, RRM
Thomas, A
Roth, M
Sheng, ZH
Esterly, N
Pinson, D
Gao, X
Zhang, YW
Ganapathy, V
Gonzalez, FJ
Guo, GL
AF Maran, Rengasamy R. M.
Thomas, Ann
Roth, Megan
Sheng, Zhonghua
Esterly, Noriko
Pinson, David
Gao, Xin
Zhang, Yawei
Ganapathy, Vadivel
Gonzalez, Frank J.
Guo, Grace L.
TI Farnesoid X Receptor Deficiency in Mice Leads to Increased Intestinal
Epithelial Cell Proliferation and Tumor Development
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID SMALL HETERODIMER PARTNER; BILE-ACID RECEPTOR; NUCLEAR RECEPTOR;
COLON-CANCER; BETA-CATENIN; ADENOMATOUS POLYPOSIS; BINDING-PROTEIN;
BREAST-CANCER; EXPRESSION; GROWTH
AB Increased dietary fat consumption is associated with colon cancer development. The exact mechanism by which fat induces colon cancer is not clear, however, increased bile acid excretion in response to high-fat diet may promote colon carcinogenesis. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, and bile acids are endogenous ligands of FXR. FXR is highly expressed in the intestine and liver where FXR is essential for maintaining bile acid homeostasis. The role of FXR in intestine cancer development is not known. The current study evaluated the effects of FXR deficiency in mice on intestinal cell proliferation and cancer development. The results showed that FXR deficiency resulted in increased colon cell proliferation, which was accompanied by an up-regulation in the expression of genes involved in cell cycle progression and inflammation, including cyclin D1 and interleukin-6. Most importantly, FXR deficiency led to an increase in the size of small intestine adenocarcinomas in adenomatous polyposis coli mutant mice. Furthermore, after treatment with a colon carcinogen, azoxymethane, FXR deficiency increased the adenocarcinoma multiplicity and size in colon and rectum of C57BL/6 mice. Loss of FXR function also increased the intestinal lymphoid nodule numbers in the intestine. Taken together, the current study is the first to show that FXR deficiency promotes cell proliferation, inflammation, and tumorigenesis in the intestine, suggesting that activation of FXR by nonbile acid ligands may protect against intestinal carcinogenesis.
C1 [Maran, Rengasamy R. M.; Thomas, Ann; Roth, Megan; Sheng, Zhonghua; Esterly, Noriko; Guo, Grace L.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
[Pinson, David] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66160 USA.
[Pinson, David] Univ Kansas, Med Ctr, Dept Lab Anim Resources, Kansas City, KS 66160 USA.
[Gao, Xin] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Ganapathy, Vadivel] Med Coll Georgia, Dept Biochem, Augusta, GA 30912 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Guo, GL (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM lguo@kumc.edu
OI Roth, Megan/0000-0002-6657-9292
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute; National Institutes of Health [R01-DK81343,
K12-HD052027, P20-RR015563, P20-RR021940]; Kansas Masonic Cancer
Research Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health National Cancer Institute; by the
National Institutes of Health [ Grants R01-DK81343, K12-HD052027,
P20-RR015563, P20-RR021940]; and by the Kansas Masonic Cancer Research
Institute.
NR 37
TC 87
Z9 90
U1 0
U2 5
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 FEB
PY 2009
VL 328
IS 2
BP 469
EP 477
DI 10.1124/jpet.108.145409
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 396WZ
UT WOS:000262623600012
PM 18981289
ER
PT J
AU Zhao, CX
Xu, XZ
Cui, YH
Wang, PH
Wei, X
Yang, SL
Edin, ML
Zeldin, DC
Wang, DW
AF Zhao, Chun Xia
Xu, Xizhen
Cui, Yinghua
Wang, Peihua
Wei, Xin
Yang, Shilin
Edin, Matthew L.
Zeldin, Darryl C.
Wang, Dao Wen
TI Increased Endothelial Nitric-Oxide Synthase Expression Reduces
Hypertension and Hyperinsulinemia in Fructose-Treated Rats
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PROTEIN-KINASE-B; INDUCED INSULIN-RESISTANCE; DIABETES-MELLITUS;
GENE-THERAPY; SIGNALING PATHWAYS; METABOLIC SYNDROME; MUSCLE;
ACTIVATION; ANGIOGENESIS; MECHANISMS
AB Endothelial dysfunction and decreased production of nitric oxide (NO) by endothelial NO synthase (eNOS) are implicated in the pathogenesis of hypertension and insulin resistance. Because the potential influence of increased eNOS expression/activity on these parameters is unclear, the present study examined the effects of eNOS gene therapy on insulin resistance and blood pressure alterations in a fructose-induced hypertension model in rats. As predicted, 2 weeks of fructose consumption in the drinking water resulted in elevated systolic blood pressure and insulin resistance. These and other physiologic alterations were reversed within 2 weeks after a single intravenous injection of a vector containing the human eNOS cDNA (pcDNA3.1-eNOS), whereas injection of an empty vector (pcDNA3.1) was without effect. In support of the beneficial effects of pcDNA3.1-eNOS treatment being because of enhanced eNOS expression and activity, increased eNOS protein levels were documented in aorta, liver, kidney, and heart of fructose-treated rats injected with pcDNA3.1-eNOS, and corresponding elevations in nitrite/nitrate and cGMP concentrations were observed in urine. Furthermore, pcDNA3.1-eNOS treatment prevented fructose-induced decreases in expression levels of insulin receptor substrate-1, the p110 catalytic subunit of phosphatidylinositol 3-kinase, phosphorylated Akt, and phosphorylated AMP-activated protein kinases in liver, aorta, and skeletal muscle. The results of this study cumulatively indicate that gene therapy with human eNOS decreased fructose-induced hypertension and insulin resistance in rats and suggest potential signaling pathways that mediate these effects. These data highlight the potential utility of eNOS gene therapy in the treatment of hypertension and insulin resistance.
C1 [Zhao, Chun Xia; Xu, Xizhen; Cui, Yinghua; Wang, Peihua; Wei, Xin; Yang, Shilin; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
[Zhao, Chun Xia; Xu, Xizhen; Cui, Yinghua; Wang, Peihua; Wei, Xin; Yang, Shilin; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan 430030, Peoples R China.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
OI Edin, Matthew/0000-0002-7042-500X
FU Intramural NIH HHS
NR 41
TC 37
Z9 40
U1 1
U2 8
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 FEB
PY 2009
VL 328
IS 2
BP 610
EP 620
DI 10.1124/jpet.108.143396
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 396WZ
UT WOS:000262623600028
PM 19008412
ER
PT J
AU Perdivara, I
Petrovich, R
Allinquant, B
Deterding, LJ
Tomer, KB
Przybylski, M
AF Perdivara, Irina
Petrovich, Robert
Allinquant, Bernadette
Deterding, Leesa J.
Tomer, Kenneth B.
Przybylski, Michael
TI Elucidation of O-Glycosylation Structures of the beta-Amyloid Precursor
Protein by Liquid Chromatography-Mass Spectrometry Using Electron
Transfer Dissociation and Collision Induced Dissociation
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE beta-Amyloid; amyloid-precursor protein; Alzheimer's disease;
O-glycosylation; tandem-mass spectrometry; electron
transfer-dissociation; collision-induced dissociation
ID TRANSFER ION/ION REACTIONS; HAMSTER OVARY CELLS; QUADRUPOLE ION-TRAP;
CAPTURE DISSOCIATION; ALZHEIMERS-DISEASE; SECRETASE CLEAVAGE;
SIDE-CHAIN; IDENTIFICATION; PEPTIDES; LOCALIZATION
AB Accumulation and deposition of beta-amyloid peptide, a major constituent in neuritic plaques are hallmarks of Alzheimer's disease (AD) and AD-related neurodegenerative diseases. beta-Amyloid (A beta) is derived from the proteolytic cleavage of amyloid precursor protein (APP), a transmembrane protein present in three major isoforms in brain comprising 695, 751 and 770 amino acids, respectively. Among other post-translational modifications, APP is modified during maturation by N- and O-glycosylation, which are thought to be responsible for its expression and secretion. Unlike N-glycosylation, no sites of O-glycosylation of APP have previously been reported. We report here the identification of three specific O-glycosylation sites of the secreted APP695 (sAPP695) produced in CHO cells, using a combination of high-performance liquid chromatography and electrospray-tandem mass spectrometry. With the use of electron transfer dissociation and collision induced dissociation (ETD and CID), we identified type, composition and structures of the Core 1 type O-linked glycans attached at the residues Thr 291, Thr 292 and Thr 576 of the full-length APP695. The glycosylations comprise multiple short glycans, containing N-acetyl galactosamine (GalNAc), Gal-GalNAc and sialic acid terminated structures. The presence of the glycopeptides in the tryptic mixture was identified using the CID-generated sugar oxonium ions. ETD proved to be valuable for the unambiguous identification of the modified sites as ETD fragmentation occurred along the peptide backbone with little or no cleavage of the glycans. Thus, the combination of the CID and ETD techniques in LC-MS is shown here, as a powerful tool for de novo identification of O-glycosylations at unknown modification sites in proteins.
C1 [Perdivara, Irina; Petrovich, Robert; Deterding, Leesa J.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Przybylski, Michael] Univ Konstanz, Dept Chem, Lab Analyt Chem & Biopolymer Struct Anal, D-78457 Constance, Germany.
[Allinquant, Bernadette] Univ Paris 05, U894, INSERM, F-75014 Paris, France.
RP Przybylski, M (reprint author), Univ Konstanz, Dept Chem, Lab Analyt Chem & Biopolymer Struct Anal, D-78457 Constance, Germany.
EM tomer@niehs.nih.gov; Michael.Przybylski@uni-konstanz.de
RI Tomer, Kenneth/E-8018-2013
FU NIH; National Institute of Environmental Health Sciences; University of
Konstanz; Deutsche Forschungsgemeinschaft
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences. This work has
been supported in part by the University of Konstanz, and by the
Deutsche Forschungsgemeinschaft (Biopolymer-MS and FG-753). The authors
would like to thank Ms. Katina Johnson and Dr. Jason Williams for the
help provided with the Agilent software, as well as Dr. Lake Paul for
the help provided with the Western blot experiments.
NR 44
TC 70
Z9 71
U1 2
U2 35
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD FEB
PY 2009
VL 8
IS 2
SI SI
BP 631
EP 642
DI 10.1021/pr800758g
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 405AC
UT WOS:000263193300023
PM 19093876
ER
PT J
AU Reilly, KJ
Moore, CA
AF Reilly, Kevin J.
Moore, Christopher A.
TI Respiratory Movement Patterns During Vocalizations at 7 and 11 Months of
Age
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Article
DE respiration; speech; infant; motor development; physiology
ID CHEST-WALL COMPLIANCE; RIB CAGE; LUNG-VOLUME; FULL-TERM; INFANTS;
DIAPHRAGM; SPEECH; CHILDREN; KINEMATICS; NEWBORN
AB Purpose: The present investigation was designed to study the modulation of abdomen and rib cage movements during vocalization over a period of development associated with rapid decreases in the compliance of the chest wall.
Method: Rib cage and abdominal kinematics were recorded during spontaneous vocalizations in 7- and 11-month old infants. Principal component analysis was used to represent each infant's abdomen and rib cage traces as the weighted sum of a small number of principal component (PC) waveforms.
Results: The fundamental periods of infants' PC waveforms in the 11-month group were significantly shorter than those in the 7-month group. In addition, the variance contributed by PCs describing unidirectional patterns of respiratory movement decreased in the 11-month group, whereas the variances contributed by PCs describing modulated patterns of movement increased. Lastly, the extent to which abdomen and rib cage movements predicted the duration of corresponding vocalizations also increased significantly in the 11-month group compared with the 7-month group.
Conclusions: The findings of the present study were consistent with the hypothesis that decreases in the compliance of the chest wall result in more rapid modulation of chest wall movements and greater control of those movements by the developing neuromuscular system.
C1 [Reilly, Kevin J.] Northeastern Univ, Dept Speech Language Pathol & Audiol, Boston, MA 02115 USA.
[Moore, Christopher A.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
RP Reilly, KJ (reprint author), Northeastern Univ, Dept Speech Language Pathol & Audiol, 360 Huntington Ave, Boston, MA 02115 USA.
EM k.reilly@neu.edu
FU NIDCD NIH HHS [F31 DC000295, F31 DC00295, R01 DC000822, R01 DC00822, T32
DC000033, T32 DC00033]
NR 40
TC 5
Z9 5
U1 0
U2 2
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1092-4388
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD FEB 1
PY 2009
VL 52
IS 1
BP 223
EP 239
DI 10.1044/1092-4388(2008/06-0215)
PG 17
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 400EJ
UT WOS:000262850500016
PM 18695025
ER
PT J
AU Appaneal, RN
Levine, BR
Perna, FM
Roh, JL
AF Appaneal, Renee Newcomer
Levine, Beverly Rockhill
Perna, Frank M.
Roh, Joni L.
TI Measuring Postinjury Depression Among Male and Female Competitive
Athletes
SO JOURNAL OF SPORT & EXERCISE PSYCHOLOGY
LA English
DT Article
DE measurement; major depressive disorder; mental health; sport injury;
psychological response
ID STRUCTURED INTERVIEW GUIDE; SEASON-ENDING INJURIES; HAMILTON
RATING-SCALE; SPORT INJURY; IMMUNE FUNCTION; ADOLESCENTS; RESPONSES;
ISSUES; RISK; PREVENTION
AB Depression is common among athletes following sport injury, yet few studies have explored the severity of postinjury depression. Among those studies, only one examined gender differences although women in the general population are more likely than men to experience depression. No research to date has used interviews to assess depression despite their standard use among mental health professionals. In a quasi-experimental design, we used a self-report checklist and a clinical interview to compare depression among male and female athletes at I week, I month, and 3 months postinjury. Results revealed significant effects of group (injured vs. control) and time (since injury), and these effects were different for the two depression measures. We also explored the sensitivity and specificity of the user-rated checklist in identifying severely depressed athletes compared with the interview. Findings underscore the importance of multimodal approaches and clinical judgment when evaluating athletes' postinjury depression symptoms.
C1 [Appaneal, Renee Newcomer] Univ N Carolina, Dept Exercise & Sport Sci, Greensboro, NC 27412 USA.
[Levine, Beverly Rockhill] Univ N Carolina, Dept Publ Hlth Educ, Greensboro, NC 27412 USA.
[Perna, Frank M.] NCI, Behav Res Proram, Hlth Promot Res Branch, Bethesda, MD 20892 USA.
[Roh, Joni L.] Calif Univ Penn, Dept Hlth Sci & Sport Studies, California, PA USA.
RP Appaneal, RN (reprint author), Univ N Carolina, Dept Exercise & Sport Sci, Greensboro, NC 27412 USA.
FU West Virginia University Office of Research; National Athletic Trainers'
Association
FX This research was supported by grants to Dr. Perna (PI) from the West
Virginia University Office of Research and the National Athletic
Trainers' Association.
NR 56
TC 23
Z9 24
U1 3
U2 20
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 0895-2779
J9 J SPORT EXERCISE PSY
JI J. Sport Exerc. Psychol.
PD FEB
PY 2009
VL 31
IS 1
BP 60
EP 76
PG 17
WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology;
Sport Sciences
SC Social Sciences - Other Topics; Psychology; Sport Sciences
GA 411MV
UT WOS:000263654600005
PM 19325188
ER
PT J
AU Stevens, HE
Leckman, JF
Coplan, JMD
Suomi, SJ
AF Stevens, Hanna E.
Leckman, James F.
Coplan, Jere My D.
Suomi, Stephen J.
TI Risk and Resilience: Early Manipulation of Macaque Social Experience and
Persistent Behavioral and Neurophysiological Outcomes
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Review
DE primates; maternal care; attachment; hypothalamic-pituitary-adrenal
axis; neurophysiology
ID CORTICOTROPIN-RELEASING-FACTOR; TRANSPORTER GENE VARIATION; INFANT
RHESUS-MONKEYS; CEREBROSPINAL-FLUID CONCENTRATIONS; VARIABLE FORAGING
DEMAND; EARLY REARING CONDITIONS; BIOGENIC-AMINE ACTIVITY; EARLY-LIFE
STRESSORS; SEROTONIN TRANSPORTER; NONHUMAN-PRIMATES
AB Objective: To review the contributions of research on nonhuman primates, specifically macaque monkeys, to the understanding of early social stress and its effects on behavior and neurophysiology. Method: Review and synthesis of two bodies of work on macaque monkeys and early social manipulation: peer rearing and variable foraging demands. The literature was searched with Medline using key terms macaque, variable foraging, and peer rearing. The reference lists of these articles were also used to generate potential studies for review. Results: Nonhuman primate macaques show similarities to humans in their social development and functioning. Peer rearing of young macaques and rearing of young macaques with mothers experiencing variable foraging conditions both result in increased anxious, impulsive, and aggressive temperament and behavior; more reactive stress physiology; altered neurotransmitter functioning; and immune and metabolic changes. Functional variants of specific genes that code for neuromodulators are mediators of these effects. Conclusions: Disrupted social relations during macaque rearing contribute to the risk for developing emotional and neurophysiological disturbance. In the face of such disruption, certain genotypes contribute to resilience. This can be alternately stated that, for animals of high-risk genotypes, resilience is conferred by quality relationships during rearing. This interaction of genetics with early social environment also applies to child mental health, implicating biological mediators identified in macaques as contributing to more complex outcomes in humans. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(2):114-127.
C1 [Stevens, Hanna E.; Leckman, James F.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Bethesda, MD USA.
RP Stevens, HE (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, 230 S Frontage Rd, New Haven, CT 06520 USA.
EM hanna.stevens@yale.edu
RI Stevens, Hanna/M-4104-2016
FU Yale Child Study Center
FX Financial support was provided by Yale Child Study Center Albert J.
Solnit Integrated Training Program.
NR 80
TC 56
Z9 56
U1 0
U2 39
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD FEB
PY 2009
VL 48
IS 2
BP 114
EP 127
DI 10.1097/CHI.0b013e318193064c
PG 14
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 397XO
UT WOS:000262695900004
PM 19127170
ER
PT J
AU Kennard, BD
Silva, SG
Tonev, S
Rohde, P
Hughes, JL
Vitiello, B
Kratochvil, CJ
Curry, JF
Emslie, GJ
Reinecke, M
Nlkrch, J
AF Kennard, Betsy D.
Silva, Susan G.
Tonev, Simon
Rohde, Paul
Hughes, Jennifer L.
Vitiello, Benedetto
Kratochvil, Christopher J.
Curry, John F.
Emslie, Graham J.
Reinecke, Mark
Nlkrch, John
TI Remission and Recovery in the Treatment for Adolescents With Depression
Study (TADS): Acute and Long-Term Outcomes
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE adolescent depression; remission; residual symptoms; recovery
ID COGNITIVE-BEHAVIORAL TREATMENT; PLACEBO-CONTROLLED TRIAL; RESIDUAL
SYMPTOMS; PSYCHOTHERAPY TRIAL; MAJOR DEPRESSION; CLINICAL-TRIAL;
DISORDER; THERAPY; CHILDREN; RELAPSE
AB Objective: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS). Method: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission. Results: At week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive-behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36. Conclusions: Most depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(2):186-195.
C1 [Kennard, Betsy D.; Hughes, Jennifer L.; Emslie, Graham J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Silva, Susan G.; Tonev, Simon] Duke Univ, Med Ctr, Clin Res Inst, Durham, NC 27706 USA.
[Rohde, Paul] Oregon Res Inst, Albuquerque, NM USA.
[Vitiello, Benedetto] NIH, Div Serv & Intervent Res, Bethesda, MD USA.
[Kratochvil, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Curry, John F.; Reinecke, Mark] Northwestern Univ, Evanston, IL 60208 USA.
RP Kennard, BD (reprint author), Univ Texas SW Med Ctr Dallas, 53233 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Beth.kennard@utsouthwestern.edu
FU National Institute of Mental Health to Duke University Medical Center
[N01 MH80008]
FX The Treatment for Adolescents with Depression Study (TADS) is supported
by contract N01 MH80008 from the National Institute of Mental Health to
Duke University Medical Center (Dr. March, Principal Investigator).
NR 41
TC 64
Z9 65
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD FEB
PY 2009
VL 48
IS 2
BP 186
EP 195
DI 10.1097/CHI.0b013e31819176f9
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 397XO
UT WOS:000262695900011
PM 19127172
ER
PT J
AU Katz, KA
Roseman, JE
Roseman, RL
Katz, SI
AF Katz, Kenneth A.
Roseman, Julie E.
Roseman, Robert L.
Katz, Stephen I.
TI Dermatitis herpetiformis flare associated with use of triiodomethane
packing strips for alveolar osteitis
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
ID IODINE
C1 [Roseman, Julie E.] Emory Univ, Atlanta, GA 30322 USA.
[Roseman, Robert L.] Vitreo Retinal Associates, Gainesville, FL USA.
[Katz, Stephen I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Katz, KA (reprint author), 1360 Mission St,Ste 401, San Francisco, CA 94103 USA.
EM kenneth.katz@gmail.com
FU Intramural NIH HHS [Z01 SC003657-33, Z99 AR999999]
NR 7
TC 5
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD FEB
PY 2009
VL 60
IS 2
BP 352
EP 353
DI 10.1016/j.jaad.2008.08.041
PG 2
WC Dermatology
SC Dermatology
GA 396UW
UT WOS:000262617700031
PM 19150286
ER
PT J
AU Powell, AC
Casey, K
Liewehr, DJ
Hayanga, A
James, TA
Cherr, GS
AF Powell, Anathea C.
Casey, Kathleen
Liewehr, David J.
Hayanga, Awori
James, Ted A.
Cherr, Gregory S.
TI Results of a National Survey of Surgical Resident Interest in
International Experience, Electives, and Volunteerism
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID COUNTRIES; SURGERY
AB BACKGROUND: Data are emerging about the essential nature of sustainable global surgical care and interest among North American surgeons. Currently, there is no formal mechanism for US surgical residents to participate in international training opportunities. A small, single-institution survey found that general surgery residents at New York University are highly motivated to pursue international training. But little research has addressed the attitudes of North American residents about international training. The goal of this study was to acquire a broader understanding of surgical resident interest in international training.
STUDY DESIGN: A structured questionnaire was administered anonymously and voluntarily to all American College of Surgeons resident members.
RESULTS: Seven hundred twenty-four residents completed surveys. Ninety-four percent of respondents planned careers in general surgery. Ninety-two percent of respondents were interested in an international elective, and 82% would prioritize the experience over all or some other electives. Fifty-four percent and 73% of respondents would be willing to use vacation and participate even if cases were not counted for graduation requirements, respectively. Educational indebtedness was high among respondents (50% of respondents carried >= $100,000 debt). Despite debt, 85% of respondents plan to volunteer while in practice. The most frequent barriers identified by respondents were financial (61%) and logistic (66%).
CONCLUSIONS: American College of Surgeons resident members are highly motivated to acquire international training experience, with many planning to volunteer in the future. A consensus among stake-holders in North American surgical education is needed to further explore international training within surgical residency. (J Am Coll Surg 2009;208:304-312. (C) 2009 by the American College of Surgeons)
C1 [Powell, Anathea C.] NYU, Sch Med, Dept Surg, New York, NY 10016 USA.
[Hayanga, Awori] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[James, Ted A.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA.
[Powell, Anathea C.; Casey, Kathleen] Amer Coll Surg, Operat Giving Back & Educ Comm, Chicago, IL USA.
[Powell, Anathea C.; Hayanga, Awori; James, Ted A.; Cherr, Gregory S.] Amer Coll Surg, Resident Associate Soc, Chicago, IL USA.
[Liewehr, David J.] NCI, Biostat & Data Management Sect, Off Clin Director, CCR, Bethesda, MD 20892 USA.
[Cherr, Gregory S.] SUNY Buffalo, Dept Surg, Buffalo, NY 14260 USA.
[Cherr, Gregory S.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Powell, AC (reprint author), NYU, Sch Med, Dept Surg, New York, NY 10016 USA.
EM powela@1enyumc.org
NR 18
TC 67
Z9 67
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD FEB
PY 2009
VL 208
IS 2
BP 304
EP 312
DI 10.1016/j.jamcollsurg.2008.10.025
PG 9
WC Surgery
SC Surgery
GA 407TP
UT WOS:000263387500019
PM 19228545
ER
PT J
AU Rovner, AJ
Nansel, TR
Gellar, L
AF Rovner, Alisha J.
Nansel, Tonja R.
Gellar, Lauren
TI The Effect of a Low-Glycemic Diet vs a Standard Diet on Blood Glucose
Levels and Macronutrient Intake in Children with Type 1 Diabetes
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
ID INDEX FOODS; OBESITY; ADVICE; YOUTH
AB A low-glycemic index (GI) diet may lower postprandial hyperglycemia and decrease the risk for postabsorptive hypoglycemia in people with type 1 diabetes. However, insufficient evidence exists on the efficacy of a low-GI diet to support practice recommendations. The goal of this study was to examine the blood glucose response to and the macronutrient composition of low-GI meals vs usual meals consumed ad libitum at home in children with type 1 diabetes. A within-subject, crossover design was employed. Twenty-three participants were recruited between June and August 2006. Participants wore a continuous blood glucose monitoring system and completed diet diaries on 2 days. On 1 day, participants consumed their usual meal; on another day, participants consumed low-GI meals ad libidum. Order of the 2 days was counterbalanced. The mean GI was 34 +/- 6 for the low-GI day and 57 6 for the usual meal day (P<0.0001). During the low-GI day, mean daytime blood glucose values (125 +/- 28 mg/dL [6.9 +/- 1.5 nmol/L] vs 185 +/- 58 mg/dL [10.3 +/- 3.2 nmol/L], P<0.001), blood glucose area above 180 mg/dL (4,486 +/- 6,138 vs 26,707 +/- 25,038, P<0.006), and high blood glucose index (5.1 +/- 5.1 vs 13.6 +/- 7.6, P<0.001) were lower compared to the usual mean day. During the low-GI day, subjects consumed more fiber (24.5 +/- 12.3 g vs 14.5 +/- 6.1 g, P<0.007) and less fat (45.7 +/- 12.2 g vs 76.8 +/- 32.4 g, P<0.005); however, there were no differences in energy, carbohydrate, or protein intake. In this pilot study, a low-GI diet was associated with improved diet quality and a reduction in hyperglycemia.
C1 [Rovner, Alisha J.; Nansel, Tonja R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gellar, Lauren] Univ Manchester, Sch Med, Clin & Populat Hlth Res Div, Worcester, MA USA.
RP Rovner, AJ (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Execut Blvd,Room 7B13R,MSC 7500, Bethesda, MD 20892 USA.
EM rouneral@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595
FU Intramural NIH HHS [Z01 HD008805-01]
NR 24
TC 20
Z9 22
U1 0
U2 4
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD FEB
PY 2009
VL 109
IS 2
BP 303
EP 307
DI 10.1016/j.jada.2008.10.047
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 401CI
UT WOS:000262915500016
PM 19167958
ER
PT J
AU Wright, RM
Roumani, YF
Boudreau, R
Newman, AB
Ruby, CM
Studenski, SA
Shorr, RI
Bauer, DC
Simonsick, EM
Hilmer, SN
Hanlon, JT
AF Wright, Rollin M.
Roumani, Yazan F.
Boudreau, Robert
Newman, Anne B.
Ruby, Christine M.
Studenski, Stephanie A.
Shorr, Ronald I.
Bauer, Douglas C.
Simonsick, Eleanor M.
Hilmer, Sarah N.
Hanlon, Joseph T.
CA Hlth Aging & Body Composition Stud
TI Effect of Central Nervous System Medication Use on Decline in Cognition
in Community-Dwelling Older Adults: Findings from the Health, Aging and
Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cognition; aged; medications
ID BENZODIAZEPINE USE; ELDERLY PERSONS; INFLAMMATORY MARKERS; FUNCTIONAL
DECLINE; PREDICTIVE MODEL; RISK-FACTORS; DRUG-USE; DELIRIUM; IMPAIRMENT;
PERFORMANCE
AB To evaluate whether combined use of multiple central nervous system (CNS) medications over time is associated with cognitive change.
Longitudinal cohort study.
Pittsburgh, Pennsylvania, and Memphis, Tennessee.
Two thousand seven hundred thirty-seven healthy adults (aged >= 65) enrolled in the Health, Aging and Body Composition study without baseline cognitive impairment (modified Mini-Mental State Examination (3MS) score >= 80).
CNS medication (benzodiazepine- and opioid-receptor agonists, antipsychotics, antidepressants) use, duration, and dose were determined at baseline (Year 1) and Years 3 and 5. Cognitive function was measured using the 3MS at baseline and Years 3 and 5. The outcome variables were incident cognitive impairment (3MS score < 80) and cognitive decline (>= 5-point decline on 3MS). Multivariable interval-censored survival analyses were conducted.
By Year 5, 7.7% of subjects had incident cognitive impairment; 25.2% demonstrated cognitive decline. CNS medication use increased from 13.9% at baseline to 15.3% and 17.1% at Years 3 and 5, respectively. It was not associated with incident cognitive impairment (adjusted hazard ratio (adj HR)=1.11, 95% confidence interval (CI)=0.73-1.69) but was associated with cognitive decline (adj HR 1.37, 95% CI=1.11-1.70). Longer duration (adj HR=1.39, CI=1.08-1.79) and higher doses (> 3 standardized daily doses) (adj HR=1.87, 95% CI=1.25-2.79) of CNS medications suggested greater risk of cognitive decline than with nonuse.
Combined use of CNS medications, especially at higher doses, appears to be associated with cognitive decline in older adults. Future studies must explore the effect of combined CNS medication use on vulnerable older adults.
C1 [Wright, Rollin M.; Roumani, Yazan F.; Newman, Anne B.; Studenski, Stephanie A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA.
[Boudreau, Robert; Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.
[Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA.
[Studenski, Stephanie A.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Gainesville, FL USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Simonsick, Eleanor M.] Johns Hopkins Univ, Inst Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Simonsick, Eleanor M.; Hilmer, Sarah N.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Hilmer, Sarah N.] Univ Sydney, Sydney, NSW 2006, Australia.
[Hilmer, Sarah N.] Royal N Shore Hosp, Sydney, NSW, Australia.
RP Wright, RM (reprint author), Univ Pittsburgh, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM rmw27@pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Hilmer, Sarah/0000-0002-5970-1501;
Boudreau, Robert/0000-0003-0162-5187
FU National Institutes of Health (NIH), National Institute on Aging; NIH c
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01AG027017]; Pittsburgh
Claude D. Pepper Older Americans Independence Center [P30AG024827]; John
A. Hartford Foundation Center
FX Sponsors' Roles: The organizations that funded this study did not
influence the interpretation of the data or the development of this
manuscript.
NR 53
TC 37
Z9 38
U1 2
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 FEB
PY 2009
VL 57
IS 2
BP 243
EP 250
DI 10.1111/j.1532-5415.2008.02127.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 399WE
UT WOS:000262829200008
PM 19207141
ER
PT J
AU Cesari, M
Kritchevsky, SB
Newman, AB
Simonsick, EM
Harris, TB
Penninx, BW
Brach, JS
Tylavsky, FA
Satterfield, S
Bauer, DC
Rubin, SM
Visser, M
Pahor, M
AF Cesari, Matteo
Kritchevsky, Stephen B.
Newman, Anne B.
Simonsick, Eleanor M.
Harris, Tamara B.
Penninx, Brenda W.
Brach, Jennifer S.
Tylavsky, Frances A.
Satterfield, Suzanne
Bauer, Doug C.
Rubin, Susan M.
Visser, Marjolein
Pahor, Marco
CA Hlth Aging & Body Composition Stud
TI Added Value of Physical Performance Measures in Predicting Adverse
Health-Related Events: Results from the Health, Aging and Body
Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE Short Physical Performance Battery; functional limitation; death;
hospitalization; usual gait speed
ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; FUNCTIONAL DEPENDENCE;
ELDERLY PEOPLE; WOMENS HEALTH; WALKING SPEED; OLDER WOMEN; GAIT SPEED;
MORTALITY; RELIABILITY
AB To determine how three different physical performance measures (PPMs) combine for added utility in predicting adverse health events in elders.
Prospective cohort study.
Health, Aging and Body Composition Study.
Three thousand twenty-four well-functioning older persons (mean age 73.6).
Timed gait, repeated chair stands, and balance (semi- and full-tandem, and single leg stands each held for 30 seconds) tests were administered at baseline. Usual gait speed was categorized to distinguish high- and low-risk participants using the previously established 1-m/s cutpoint. The same population-percentile (21.3%) was used to identify cutpoints for the repeated chair stands (17.1 seconds) and balance (53.0 seconds) tests. Cox proportional hazard analyses were performed to evaluate the added value of PPMs in predicting mortality, hospitalization, and (severe) mobility limitation events over 6.9 years of follow-up.
Risk estimates for developing adverse health-related events were similarly large for each of the three high-risk groups considered separately. Having more PPM scores at the high-risk level was associated with a greater risk of developing adverse health-related events. When all three PPMs were considered, having only one poor performance was sufficient to indicate a highly significantly higher risk of (severe) lower extremity and mortality events.
Although gait speed is considered to be the most important predictor of adverse health events, these findings demonstrate that poor performance on other tests of lower extremity function are equally prognostic. This suggests that chair stand and standing balance performance may be adequate substitutes when gait speed is unavailable.
C1 [Cesari, Matteo; Pahor, Marco] Univ Florida, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27103 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Tylavsky, Frances A.; Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Bauer, Doug C.; Rubin, Susan M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Bauer, Doug C.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands.
RP Cesari, M (reprint author), Univ Florida, Inst Aging, Dept Aging & Geriatr Res, 210 E Mowry Rd, Gainesville, FL 32611 USA.
EM macesari@gmail.com
RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013;
OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging (NIA) [N01-AG-6-2106, N01-AG-6-2101,
N01-AG-6-2103]; University of Florida Institute on Aging; Claude D.
Pepper Older Americans Independence Center (National Institutes of
Health (NIH) [1P30AG028740]
FX Sponsor's Role: None.
NR 26
TC 144
Z9 149
U1 3
U2 14
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 FEB
PY 2009
VL 57
IS 2
BP 251
EP 259
DI 10.1111/j.1532-5415.2008.02126.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 399WE
UT WOS:000262829200009
PM 19207142
ER
PT J
AU Vestergaard, S
Patel, KV
Walkup, MP
Pahor, M
Marsh, AP
Espeland, MA
Studenski, S
Gill, TM
Church, T
Guralnik, JM
AF Vestergaard, Sonja
Patel, Kushang V.
Walkup, Michael P.
Pahor, Marco
Marsh, Anthony P.
Espeland, Mark A.
Studenski, Stephanie
Gill, Thomas M.
Church, Timothy
Guralnik, Jack M.
TI Stopping to Rest During a 400-Meter Walk and Incident Mobility
Disability in Older Persons with Functional Limitations
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE mobility disability; aging; physical performance test
ID PERIPHERAL ARTERIAL-DISEASE; LIFE-STYLE INTERVENTIONS; PHYSICAL
PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; SELF-EFFICACY;
INDEPENDENCE; ADULTS; ASSOCIATION; MORTALITY; EXERCISE
AB To examine the association between stopping to rest during a 400-m usual-pace walk test (400-MWT) and incident mobility disability in older persons with functional limitations.
Prospective cohort study.
Community based.
Four hundred twenty-four participants in the Lifestyle Intervention and Independence for Elders Pilot (LIFE-P) Study aged 70 to 89 with functional limitations (summary score <= 9 on the Short Physical Performance Battery (SPPB)) but able to complete the 400-MWT within 15 minutes.
Rest stops during the 400-MWT were recorded. The onset of mobility disability, defined as being unable to complete the 400-MWT or taking more than 15 minutes to do so, was recorded at Months 6 and 12.
Fifty-four (12.7%) participants rested during the 400-MWT at baseline, of whom 37.7% experienced mobility disability during follow-up, versus 8.6% of those not stopping to rest. Performing any rest stop was strongly associated with incident mobility disability at follow-up (odds ratio (OR)=5.4, 95% confidence interval (CI)=2.7-10.9) after adjustment for age, sex, and clinic site. This association was weaker, but remained statistically significant, after further adjusting for SPPB and time to complete the 400-MWT simultaneously (OR=2.6, 95% CI=1.2-5.9).
Stopping to rest during the 400-MWT is strongly associated with incident mobility disability in nondisabled older persons with functional limitations. Given the prognostic value, rest stops should be recorded as part of the standard assessment protocol for the 400-MWT.
C1 [Vestergaard, Sonja; Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Walkup, Michael P.; Espeland, Mark A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Marsh, Anthony P.] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[Pahor, Marco] Univ Florida, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Studenski, Stephanie] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA.
[Gill, Thomas M.] Yale Univ, Dept Internal Med Geriatr, New Haven, CT USA.
[Church, Timothy] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA.
RP Vestergaard, S (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Suite 3C309, Bethesda, MD 20892 USA.
EM vestergaards@mail.nih.gov
FU Cooperative Agreement with the National Institute on Aging (NIA) [UO1
AG022376]; National Institutes of Health; NIA [K24AG021507, AG024827,
AG023641]
FX Sponsor's Role: The granting institutions named above did not interfere
in any way with the design, methods, participant recruitment, data
collection or analysis, or preparation of the manuscript.
NR 18
TC 9
Z9 9
U1 0
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 FEB
PY 2009
VL 57
IS 2
BP 260
EP 265
DI 10.1111/j.1532-5415.2008.02097.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 399WE
UT WOS:000262829200010
PM 19170785
ER
PT J
AU Yeganova, L
Comeau, DC
Kim, W
Wilbur, WJ
AF Yeganova, Lana
Comeau, Donald C.
Kim, Won
Wilbur, W. John
TI How to Interpret PubMed Queries and Why It Matters
SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY
LA English
DT Article
ID OF-THE-LITERATURE; INFORMATION-SCIENCE; RELEVANCE; FRAMEWORK; THINKING;
SYSTEMS; NOTION
AB A significant fraction of queries in PubMed (TM) are multiterm queries without parsing instructions. Generally, search engines interpret such queries as collections of terms, and handle them as a Boolean conjunction of these terms. However, analysis of queries in PubMed (TM) indicates that many such queries are meaningful phrases, rather than simple collections of terms. In this study, we examine whether or not it makes a difference, in terms of retrieval quality, if such queries are interpreted as a phrase or as a conjunction of query terms. And, if it does, what is the optimal way of searching with such queries. To address the question, we developed an automated retrieval evaluation method, based on machine learning techniques, that enables us to evaluate and compare various retrieval outcomes. We show that the class of records that contain all the search terms, but not the phrase, qualitatively differs from the class of records containing the phrase. We also show that the difference is systematic, depending on the proximity of query terms to each other within the record. Based on these results, one can establish the best retrieval order for the records. Our findings are consistent with studies in proximity searching.
C1 [Yeganova, Lana; Comeau, Donald C.; Kim, Won; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA.
RP Yeganova, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM yeganova@mail.nih.gov; comeau@mail.nih.gov; wonkim@mail.nih.gov;
wilbur@mail.nih.gov
FU National Institutes of Health-National Librarv of Medicine(TM)
FX The authors are Supported by the Intramural Research Program of the
National Institutes of Health-National Librarv of Medicine (TM).
NR 14
TC 8
Z9 8
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1532-2882
J9 J AM SOC INF SCI TEC
JI J. Am. Soc. Inf. Sci. Technol.
PD FEB
PY 2009
VL 60
IS 2
BP 264
EP 274
DI 10.1002/asi.20979
PG 11
WC Computer Science, Information Systems; Information Science & Library
Science
SC Computer Science; Information Science & Library Science
GA 404FK
UT WOS:000263136200005
ER
PT J
AU Jackson, SN
Dutta, S
Woods, AS
AF Jackson, Shelley N.
Dutta, Sucharita
Woods, Amina S.
TI The Use of ECD/ETD to Identify the Site of Electrostatic Interaction in
Noncovalent Complexes
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; CAPTURE DISSOCIATION; MECHANISM; PEPTIDE
AB Electrostatic interactions play an important role in the formation of noncovalent complexes. Our previous work has highlighted the role of certain amino acid residues, Such as arginine, glutamate, aspartate, and phosphorylated/sulfated residues, in the formation of salt bridges resulting in noncovalent complexes between peptides. Tandem mass spectrometry (MS) studies of these complexes using collision-induced dissociation (CID) have provided information on their relative stability. However, product-ion spectra produced by CID have been unable to assign specifically the site of interaction for the complex. In this work, tandem MS experiments were conducted on noncovalent complexes using both electron capture dissociation (ECD) and electron-transfer dissociation (ETD). The resulting spectra were dominated by intramolecular fragments of the complex with the electrostatic interaction site intact. Based upon these data, we were able to assign the binding site for the peptides forming the noncovalent complex. (J Am Soc Mass Spectrom 2009, 20, 176-179) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
C1 [Jackson, Shelley N.; Woods, Amina S.] NIDA, IRP, NIH, Baltimore, MD 21224 USA.
[Dutta, Sucharita] Thermo Fisher Sci, San Jose, CA USA.
RP Woods, AS (reprint author), NIDA, IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM awoods@intra.nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 15
TC 23
Z9 23
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD FEB
PY 2009
VL 20
IS 2
BP 176
EP 179
DI 10.1016/j.jasms.2008.08.021
PG 4
WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 402HJ
UT WOS:000263004500002
PM 18835725
ER
PT J
AU Olson, MT
Yergey, AL
AF Olson, Matthew T.
Yergey, Alfred L.
TI Calculation of the Isotope Cluster for Polypeptides by Probability
Grouping
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID RESONANCE MASS-SPECTROMETRY; FOURIER-TRANSFORM; ABUNDANCE CALCULATIONS;
DISTRIBUTIONS; SPECTRA; DECONVOLUTION; PROTEOMICS; REDUCTION; PATTERNS;
PEAKS
AB This paper presents a novel theoretical basis for accurately calculating the isotope cluster of polypeptides. In contrast to previous approaches to this problem, which consider exhaustive or near exhaustive combinations of isotopic species, the program, Neutron Cluster, groups probabilities to yield highly accurate information without elucidating any fine structure within a nominal mass unit. This is a fundamental difference from any previously described algorithm for calculating the isotope cluster. As a result of this difference, the accurate isotope clusters for high molecular weight polypeptides can be calculated rapidly without any pruning. When applied to isotope enriched polypeptides, the algorithm introduces "grouping error", which is described, quantified, and avoided by using probability partitioning. 0 Am Soc Mass Spectrom 2009, 20, 295-302) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
C1 [Olson, Matthew T.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA.
[Olson, Matthew T.; Yergey, Alfred L.] NICHHD, Sect Metab & Mass Spectrometry, NIH, Baltimore, MD USA.
RP Olson, MT (reprint author), Johns Hopkins Med Inst, Dept Pathol, Carnegie 400,600 N Wolfe St, Baltimore, MD 21287 USA.
EM Molson8@jhmi.edu
FU National Institute of Child Health and Human Development
FX The authors acknowledge support for this research by the Intramural
Research Program of the National Institute of Child Health and Human
Development. The authors gratefully acknowledge the helpful comments and
discussion of Jonathan A. Epstein (OSD/NICHD/NIH).
NR 27
TC 14
Z9 14
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD FEB
PY 2009
VL 20
IS 2
BP 295
EP 302
DI 10.1016/j.jasms.2008.10.007
PG 8
WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 402HJ
UT WOS:000263004500015
PM 19026561
ER
PT J
AU Sanchez-Nino, MD
Sanz, AB
Ihalmo, P
Lassila, M
Holthofer, H
Mezzano, S
Aros, C
Groop, PH
Saleem, MA
Mathieson, PW
Langham, R
Kretzler, M
Nair, V
Lemley, KV
Nelson, RG
Mervaala, E
Mattinzoli, D
Rastaldi, MP
Ruiz-Ortega, M
Martin-Ventura, JL
Egido, J
Ortiz, A
AF Dolores Sanchez-Nino, Maria
Belen Sanz, Ana
Ihalmo, Pekka
Lassila, Markus
Holthofer, Harry
Mezzano, Sergio
Aros, Claudio
Groop, Per-Henrik
Saleem, Moin A.
Mathieson, Peter W.
Langham, Robert
Kretzler, Matthias
Nair, Viji
Lemley, Kevin V.
Nelson, Robert G.
Mervaala, Eero
Mattinzoli, Deborah
Rastaldi, Maria Pia
Ruiz-Ortega, Marta
Luis Martin-Ventura, Jose
Egido, Jesus
Ortiz, Alberto
TI The MIF Receptor CD74 in Diabetic Podocyte Injury
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MIGRATION INHIBITORY FACTOR; TUBULAR EPITHELIAL-CELLS; ACTIVATED
PROTEIN-KINASES; PROGRESSIVE RENAL INJURY; HUMAN GLOMERULONEPHRITIS;
NEPHROPATHY; EXPRESSION; P38; APOPTOSIS; INTERFERON
AB Although metabolic derangement plays a central role in diabetic nephropathy, a better understanding of secondary mediators of injury may lead to new therapeutic strategies. Expression of macrophage migration inhibitory factor (MIF) is increased in experimental diabetic nephropathy, and increased tubulointerstitial mRNA expression of its receptor, CD74, has been observed in human diabetic nephropathy. Whether CD74 transduces MIF signals in podocytes, however, is unknown. Here, we found glomerular and tubulointerstitial CD74 mRNA expression to be increased in Pima Indians with type 2 diabetes and diabetic nephropathy. Immunohistochemistry confirmed the increased glomerular and tubular expression of CD74 in clinical and experimental diabetic nephropathy and localized glomerular CD74 to podocytes. In cultured human podocytes, CD74 was expressed at the cell surface, was upregulated by high concentrations of glucose and TNF-alpha, and was activated by MIF, leading to phosphorylation of extracellular signal-regulated kinase 1/2 and p38. High glucose also induced CD74 expression in a human proximal tubule cell line (HK2). In addition, MIF induced the expression of the inflammatory mediators TRAIL and monocyte chemoattractant protein 1 in podocytes and HK2 cells in a p38-dependent manner. These data suggest that CD74 acts as a receptor for MIF in podocytes and may play a role in the pathogenesis of diabetic nephropathy.
C1 [Dolores Sanchez-Nino, Maria; Belen Sanz, Ana; Ruiz-Ortega, Marta; Luis Martin-Ventura, Jose; Egido, Jesus; Ortiz, Alberto] Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Renal Inigo Alvarez de Toledo, Madrid 28040, Spain.
[Ihalmo, Pekka; Groop, Per-Henrik] Univ Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.
[Ihalmo, Pekka; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki, Finland.
[Lassila, Markus] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland.
[Holthofer, Harry] Dublin City Univ, Ctr Bioanalyt Sci, Dublin 9, Ireland.
[Mezzano, Sergio; Aros, Claudio] Univ Austral Chile, Div Nephrol, Valdivia, Chile.
[Saleem, Moin A.; Mathieson, Peter W.] Univ Bristol, Acad & Childrens Renal Unit, Bristol, Avon, England.
[Langham, Robert] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia.
[Kretzler, Matthias; Nair, Viji] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA.
[Lemley, Kevin V.] Childrens Hosp Los Angeles, Div Nephrol, Los Angeles, CA 90027 USA.
[Nelson, Robert G.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
[Mervaala, Eero] Univ Helsinki, Inst Biomed Pharmacol, FIN-00014 Helsinki, Finland.
[Mattinzoli, Deborah; Rastaldi, Maria Pia] Fdn DAmico Ric Malattie Renali, Milan, Italy.
RP Ortiz, A (reprint author), Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Renal Inigo Alvarez de Toledo, Avda Reyes Catolicos 2, Madrid 28040, Spain.
EM aortiz@fjd.es
RI Nelson, Robert/B-1470-2012; Ruiz-Ortega, Marta/D-3584-2012;
OI Ruiz-Ortega, Marta/0000-0002-1495-6535; Sanchez-Nino, Maria
Dolores/0000-0001-7110-6409; ruiz-ortega, marta/0000-0002-1403-2690
FU ADDNET [FIS 06/0046, SAF03/884, LSHB-CT-2004-6]; DIALOK
[LSHB-CT-2007-036644]; Sociedad Espanola de Nefrologia; ISCIII-RETIC
[REDinREN/RD06/0016]; Comunidad de Madrid [FRACM/S-BIO0283/2006];
National Institute of Diabetes and Digestive and Kidney Diseases
FX This Study was Supported by grant FIS 06/0046, SAF03/884, LSHB-CT-2004-6
(ADDNET), LSHB-CT-2007-036644 (DIALOK), Sociedad Espanola de Nefrologia,
ISCIII-RETIC REDinREN/RD06/0016, and Comunidad de
Madrid/FRACM/S-BIO0283/2006. Salary support was provided by FIS to
A.B.S., MEC to M.D.S.N., Programa Intensificacion Actividad
Investigadora (ISCIII/Agencia LainEntralgo/CM) to A.O., and the Finnish
Kidney Foundation and the Kyllikki and Uolevi Lehikoinen Foundation for
P.I. Fondecyt 1080083 to S.M. This research was supported, in part, by
the Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases.; Anneli von Behr is acknowledged for
technical assistance and Mar Gonzalez Garcia-Parreno and Alberto Puime
for technical help.
NR 33
TC 62
Z9 65
U1 3
U2 6
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD FEB
PY 2009
VL 20
IS 2
BP 353
EP 362
DI 10.1681/ASN.2008020194
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 406HE
UT WOS:000263284800018
PM 18842989
ER
PT J
AU Gonzales, PA
Pisitkun, T
Hoffert, JD
Tchapyjnikov, D
Star, RA
Kleta, R
Wang, NS
Knepper, MA
AF Gonzales, Patricia A.
Pisitkun, Trairak
Hoffert, Jason D.
Tchapyjnikov, Dmitry
Star, Robert A.
Kleta, Robert
Wang, Nam Sun
Knepper, Mark A.
TI Large-Scale Proteomics and Phosphoproteomics of Urinary Exosomes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID TANDEM MASS-SPECTRA; VACUOLAR H+-ATPASE; PHOSPHORYLATION ANALYSIS;
HYPOKALEMIC ALKALOSIS; COTRANSPORTER NKCC2; BARTTERS-SYNDROME; CL
COTRANSPORTER; IDENTIFICATION; BIOMARKERS; PHYSIOLOGY
AB Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space. Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers. We extended the proteomic analysis to phospho-proteomic profiling using neutral loss scanning, and this yielded multiple novel phosphorylation sites, including serine-811 in the thiazide-sensitive Na-Cl co-transporter, NCC. To demonstrate the potential use of exosome analysis to identify a genetic renal disease, we carried out immunoblotting of exosomes from urine samples of patients with a clinical diagnosis of Bartter syndrome type 1, showing an absence of the sodium-potassium-chloride co-transporter 2, NKCC2. The proteomic data are publicly accessible at http://dir.nhlbi.nih.gov/papers/lkem/exosome/.
C1 [Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
[Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, Bethesda, MD USA.
[Kleta, Robert] NHGRI, Sect Human Biomed Genet, Med Genet Branch, Bethesda, MD 20892 USA.
[Kleta, Robert] NIH, Off Rare Dis, Off Director, Bethesda, MD USA.
[Gonzales, Patricia A.; Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
[Kleta, Robert] UCL, Ctr Nephrol, London Epithelial Grp, London, England.
RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
RI Wang, Nam Sun/E-4253-2016;
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]
NR 28
TC 242
Z9 250
U1 8
U2 46
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD FEB
PY 2009
VL 20
IS 2
BP 363
EP 379
DI 10.1681/ASN.2008040406
PG 17
WC Urology & Nephrology
SC Urology & Nephrology
GA 406HE
UT WOS:000263284800019
PM 19056867
ER
PT J
AU Vines, AI
Baird, DD
AF Vines, Anissa I.
Baird, Donna D.
TI Stress of Caring for Children: The Role of Perceived Racism
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE race/ethnicity; racism; children/adolescents
ID AFRICAN-AMERICAN; MENTAL-HEALTH; DISCRIMINATION; WOMEN; RACE;
SOCIALIZATION; EXPERIENCES
AB Purpose: Regardless of race, most mothers experience stress related to concerns about their children. African American mothers may experience the additional stress of their child(ren) experiencing racism. We describe the stress that African American women have about their children experiencing racism.
Methods: The Telephone-Ad ministered Perceived Racism Scale (TPRS) was administered to 476 African American women ages 36 to 53 who were members of a prepaid health plan. The 8-item Concern for Children scale, I of the 5 TPRS scales, was completed by 382 women and assessed the level of concern women have about their children experiencing racism. The responses ranged from "not at all concerned" to "very concerned."
Results: For 6 of the 8 items, more than 60% reported being "very concerned" for their children. Items of highest concern involved institutionalized racism with more than 70% reported being very concerned about their children being harmed or harassed by the police or getting stopped in a predominantly white neighborhood. Respondents were less concerned about their children being considered less attractive than their white counterparts and/or being excluded from social events, activities, or groups. Level of concern was not related to income or education. Unsurprisingly, respondents who reported high levels of perceived racism also reported greater concern for their child(ren).
Conclusions: These findings highlight an additional stressor related to childrearing in a "race-conscious" society. Future research on stress and African American women's health should include this additional stressor.
C1 [Vines, Anissa I.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Vines, Anissa I.] Ethn Culture & Hlth Outcomes ECHO Program, Chapel Hill, NC USA.
[Baird, Donna D.] Natl Inst Environm Hlth Sci, Dept Epidemiol, Res Triangle Pk, NC USA.
RP Vines, AI (reprint author), Univ N Carolina, 266 Rosenau Hall,CB 7435, Chapel Hill, NC 27599 USA.
EM avines@email.unc.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU University of North Carolina; National Institute of Child Health and
Human Development; National Institutes of Health Office of the Director;
Office of Research on Women's Health; National Institute of
Environmental Health Sciences (NIEHS); National Institute of Mental
Health [1-RO3-MH61057]
FX The final preparation of this article was supported in part by the
University of North Carolina at Chapel Hill K 12 Building
Interdisciplinary Careers in Women's Health Research program funded by
the National Institute of Child Health and Human Development, the
National Institutes of Health Office of the Director, Office of Research
on Women's Health and the National Institute of Environmental Health
Sciences (NIEHS). The conceptualization of the study, data collection,
and analyses for this project were supported by the Intramural Research
Training Program at the NIEHS and by the National Institute of Mental
Health (grant 1-RO3-MH61057 to A.I.V.).
NR 16
TC 3
Z9 3
U1 2
U2 6
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD FEB
PY 2009
VL 101
IS 2
BP 156
EP 160
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 425XW
UT WOS:000264672300010
PM 19378633
ER
PT J
AU Jackson, WM
Aragon, AB
Djouad, F
Song, Y
Koehler, SM
Nesti, LJ
Tuan, RS
AF Jackson, W. M.
Aragon, A. B.
Djouad, F.
Song, Y.
Koehler, S. M.
Nesti, L. J.
Tuan, R. S.
TI Mesenchymal progenitor cells derived from traumatized human muscle
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE mesenchymal stem cells; multipotent progenitor cells; muscle stem cells;
heterotopic ossification; regenerative medicine; orthopaedic trauma
ID HUMAN BONE-MARROW; HUMAN TRABECULAR BONE; HUMAN SYNOVIAL-MEMBRANE; ADULT
STEM-CELLS; STROMAL CELLS; HETEROTOPIC OSSIFICATION; IN-VITRO;
UMBILICAL-CORD; DIFFERENTIATION; TISSUE
AB Mesenchymal stem cells (MSCs) derived from adult tissues are an important candidate cell type for cell-based tissue engineering and regenerative medicine. Currently, clinical applications for MSCs require additional surgical procedures to harvest the autologous MSCs (i.e. from bone marrow) or commercial allogeneic alternatives. We have recently identified a population of mesenchymal progenitor cells (MPCs) in traumatized muscle tissue that has been surgically debrided from traumatic orthopaedic extremity wounds. The purpose of this study was to evaluate whether MPCs derived from traumatized muscle may provide a clinical alternative to bone-marrow MSCs, by comparing their morphology, proliferation capacity, cell surface epitope profile and differentiation capacity. After digesting the muscle tissue with collagenase, the MPCs were enriched by a direct plating technique. The morphology and proliferation rate of the muscle-derived MPCs was similar to bone-marrow derived MSCs. Both populations expressed cell surface markers characteristic for MSCs (CD 73, CD 90 and CD105), and did not express markers typically absent on MSCs (CD14, CD34 and CD45). After 21 days in specific differentiation media, the histological staining and gene expression of the MPCs and MSCs was characteristic for differentiation into osteoblasts, chondrocytes and adipocytes, but not into myoblasts. Our findings demonstrate that traumatized muscle-derived MPCs exhibit a similar phenotype and resemble MSCs derived from the bone marrow. MPCs harvested from traumatized muscle tissue may be considered for applications in tissue engineering and regenerative medicine following orthopaedic trauma requiring circumferential debridement. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Jackson, W. M.; Aragon, A. B.; Djouad, F.; Song, Y.; Koehler, S. M.; Nesti, L. J.; Tuan, R. S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Aragon, A. B.; Nesti, L. J.] Walter Reed Army Med Ctr, Integrated Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 S Dr,Room 1140,MSC 8022, Bethesda, MD 20892 USA.
EM tuanr@mail.nih.gov
OI Djouad, Farida/0000-0001-8248-6822
FU WRAMC [P05-A011]; NIH NIAMS Intramural Research Program [Z01 AR41131]
FX This study was supported by the Military Amputee Research Program at
WRAMC (Grant No. P05-A011) and the NIH NIAMS Intramural Research Program
(Grant No. Z01 AR41131). FACS data were collected at the NIAMS Flow
Cytometry Section with the expert assistance of Jim Simone. Portions of
this work were performed at the Naval Surgical Research laboratory in
the National Naval Medical Center. The authors would like to thank
Michael K. Sracic and James R. Bailey for their assistance in performing
the differentiation experiments in this study.
NR 53
TC 40
Z9 44
U1 1
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1932-6254
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD FEB
PY 2009
VL 3
IS 2
BP 129
EP 138
DI 10.1002/term.149
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA 421VA
UT WOS:000264385200008
PM 19170141
ER
PT J
AU Lockenhoff, CE
Terracciano, A
Patriciu, NS
Eaton, WW
Costa, PT
AF Loeckenhoff, Corinna E.
Terracciano, Antonio
Patriciu, Nicholas S.
Eaton, William W.
Costa, Paul T., Jr.
TI Self-Reported Extremely Adverse Life Events and Longitudinal Changes in
Five-Factor Model Personality Traits in an Urban Sample
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; EPIDEMIOLOGIC CATCHMENT-AREA; YOUNG
ADULTHOOD; NEO-PI; TEMPORAL STABILITY; MAJOR DEPRESSION; TRAUMATIC
EVENTS; WORK EXPERIENCES; FOLLOW-UP; PREDICTORS
AB This study examined longitudinal personality change in response to extremely adverse life events in a sample (N= 458) drawn from the First Baltimore Epidemiologic Catchment Area study Five factor model personality traits were assessed twice over art average interval of 8 years. Twenty-five percent of the participants reported air extremely horrifying or frightening event within 2 years before the second personality assessment. Relative to the rest of the sample, they showed increases in neuroticism, decreases in tire compliance facet of agreeableness, and decreases in openness to values. Baseline personality was unrelated to future events, but among participants who reported extreme events, lower extraversion and/or conscientiousness at baseline as well as longitudinal increases in neuroticism predicted lower mental health at follow-up.
C1 [Loeckenhoff, Corinna E.; Terracciano, Antonio; Patriciu, Nicholas S.; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA.
[Eaton, William W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
RP Lockenhoff, CE (reprint author), NIA, NIH, Biomed Res Ctr, IRR 251 Bayview Blvd,Suite 100,Room 04B323, Baltimore, MD 21224 USA.
EM Loeckenhoff@gmail.com
RI terracciano, antonio/B-1884-2008;
OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa,
Paul/0000-0003-4375-1712
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000197-03, ZIA AG000197-04];
NIDA NIH HHS [R01 DA026652, R01 DA026652-16A1]; NIMH NIH HHS [K23
MH064543, MH 47447, MH 50616, MH64543, R01 MH047447, R01 MH047447-15,
R01 MH050616]
NR 43
TC 50
Z9 51
U1 7
U2 20
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD FEB
PY 2009
VL 22
IS 1
BP 53
EP 59
DI 10.1002/jts.20385
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 414TQ
UT WOS:000263888500008
PM 19230009
ER
PT J
AU Robinson, JM
Shavers, V
AF Robinson, J. M.
Shavers, V.
TI The Role of Health Insurance Coverage in Cancer Screening Utilization
SO JOURNAL OF UROLOGY
LA English
DT Article
C1 [Robinson, J. M.] NCI, Canc Prevent & Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
NCI, Off Educ & Special Initiat, Bethesda, MD 20892 USA.
RP Robinson, JM (reprint author), NCI, Canc Prevent & Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD FEB
PY 2009
VL 181
IS 2
BP 793
EP 793
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 394BJ
UT WOS:000262419900179
ER
PT J
AU Duda, A
Lee-Turner, L
Fox, J
Robinson, N
Dustan, S
Kaye, S
Fryer, H
Carrington, M
McClure, M
Mclean, AR
Fidler, S
Weber, J
Phillips, RE
Frater, AJ
AF Duda, A.
Lee-Turner, L.
Fox, J.
Robinson, N.
Dustan, S.
Kaye, S.
Fryer, H.
Carrington, M.
McClure, M.
Mclean, A. R.
Fidler, S.
Weber, J.
Phillips, R. E.
Frater, A. J.
CA SPARTAC Trail Investigators
TI HLA-Associated Clinical Progression Correlates with Epitope Reversion
Rates in Early Human Immunodeficiency Virus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; PRIMARY HIV-INFECTION; IN-VIVO; LYMPHOCYTE RESPONSES;
VIRAL LOAD; DISEASE PROGRESSION; IMMUNE-RESPONSES; TYPE-1; ESCAPE; AIDS
AB Human immunodeficiency virus type 1 (HIV-1) can evade immunity shortly after transmission to a new host but the clinical significance of this early viral adaptation in HIV infection is not clear. We present an analysis of sequence variation from a longitudinal cohort study of HIV adaptation in 189 acute seroconverters followed for up to 3 years. We measured the rates of variation within well-defined epitopes to determine associations with the HLA-linked hazard of disease progression. We found early reversion across both the gag and pol genes, with a 10-fold faster rate of escape in gag (2.2 versus 0.27 forward mutations/1,000 amino acid sites). For most epitopes (23/34), variation in the HLA-matched and HLA-unmatched controls was similar. For a minority of epitopes (8/34, and generally associated with HLA class I alleles that confer clinical benefit), new variants appeared early and consistently over the first 3 years of infection. Reversion occurred early at a rate which was HLA-dependent and correlated with the HLA class 1-associated relative hazard of disease progression and death (P = 0.0008), reinforcing the association between strong cytotoxic T-lymphocyte responses, viral fitness, and disease status. These data provide a comprehensive overview of viral adaptation in the first 3 years of infection. Our findings of HLA-dependent reversion suggest that costs are borne by some escape variants which may benefit the host, a finding contrary to a simple immune evasion paradigm. These epitopes, which are both strongly and frequently recognized, and for which escape involves a high cost to the virus, have the potential to optimize vaccine design.
C1 [Duda, A.; Lee-Turner, L.; Robinson, N.; Phillips, R. E.; Frater, A. J.] Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 3SY, England.
[Duda, A.; Lee-Turner, L.; Robinson, N.; Fryer, H.; Mclean, A. R.; Phillips, R. E.; Frater, A. J.] James Martin 21st Century Sch, Oxford OX1 3SY, England.
[Fox, J.; Dustan, S.; Kaye, S.; McClure, M.; Fidler, S.; Weber, J.] Univ London Imperial Coll Sci Technol & Med, Div Med, Wright Fleming Inst, St Marys Hosp, London W2 1PG, England.
[Fryer, H.; Mclean, A. R.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Carrington, M.] NCI, Basic Res Program, SAIC Frederick, Lab Genom Div, Frederick, MD 21701 USA.
RP Phillips, RE (reprint author), Dept Clin Med, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England.
EM rodney.phillips@ndm.ox.ac.uk
RI Beral, Valerie/B-2979-2013;
OI Frater, John/0000-0001-7163-7277
FU Wellcome Trust (United Kingdom)
FX A. D. and J. F. are supported by the MRC. J.W. and R.E.P. are supported
by the Wellcome Trust (United Kingdom).
NR 47
TC 32
Z9 32
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 FEB 1
PY 2009
VL 83
IS 3
BP 1228
EP 1239
DI 10.1128/JVI.01545-08
PG 12
WC Virology
SC Virology
GA 392TR
UT WOS:000262325600007
PM 19019964
ER
PT J
AU Davis, KL
Bibollet-Ruche, F
Li, H
Decker, JM
Kutsch, O
Morris, L
Salomon, A
Pinter, A
Hoxie, JA
Hahn, BH
Kwong, PD
Shaw, GM
AF Davis, Katie L.
Bibollet-Ruche, Frederic
Li, Hui
Decker, Julie M.
Kutsch, Olaf
Morris, Lynn
Salomon, Aidy
Pinter, Abraham
Hoxie, James A.
Hahn, Beatrice H.
Kwong, Peter D.
Shaw, George M.
TI Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras
Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in
Human Plasma
SO JOURNAL OF VIROLOGY
LA English
DT Review
ID HUMAN MONOCLONAL-ANTIBODIES; CORECEPTOR-BINDING-SITE; PRINCIPAL
NEUTRALIZING DOMAIN; EPITOPE FINE SPECIFICITY; SUBTYPE-C INFECTION; V3
LOOP; SOLUBLE CD4; CROSS-REACTIVITY; VACCINE DESIGN; CRYPTIC NATURE
AB Deciphering antibody specificities that constrain human immunodeficiency virus type 1 (HIV-1) envelope (Env) diversity, limit virus replication, and contribute to neutralization breadth and potency is an important goal of current HIV/AIDS vaccine research. Transplantation of discrete HIV-1 neutralizing epitopes into HIV-2 scaffolds may provide a sensitive, biologically functional context by which to quantify specific antibody reactivities even in complex sera. Here, we describe a novel HIV-2 proviral scaffold (pHIV-2(KR.X7)) into which we substituted the complete variable region 3 (V3) of the env gene of HIV-1(YU2) or HIV-1(Ccon) to yield the chimeric proviruses pHIV-2(KR.X7) YU2 V3 and pHIV-2(KR.X7) Ccon V3. These HIV-2/HIV-1 chimeras were replication competent and sensitive to selective pharmacological inhibitors of virus entry. V3 chimeric viruses were resistant to neutralization by HIV-1 monoclonal antibodies directed against the CD4 binding site, coreceptor binding site, and gp41 membrane proximal external region but exhibited striking sensitivity to HIV-1 V3-specific monoclonal antibodies, 447-52D and F425 B4e8 (50% inhibitory concentration of [IC(50)] <0.005 mu g/ml for each). Plasma specimens from 11 HIV-1 clade B- and 10 HIV-1 clade C-infected subjects showed no neutralizing activity against HIV-2 but exhibited high-titer V3-specific neutralization against both HIV-2/HIV-1 V3 chimeras with IC(50) measurements ranging from 1: 50 to greater than 1:40,000. Neutralization titers of B clade plasmas were as much as 1,000-fold lower when tested against the primary HIV-1(YU2) virus than with the HIV-2(KR.X7) YU2 V3 chimera, demonstrating highly effective shielding of V3 epitopes in the native Env trimer. This finding was replicated using a second primary HIV-1 strain (HIV-1(BORI)) and the corresponding HIV-2(KR.X7) BORI V3 chimera. We conclude that V3 is highly immunogenic in vivo, eliciting antibodies with substantial breadth of reactivity and neutralizing potential. These antibodies constrain HIV-1 Env to a structure(s) in which V3 epitopes are concealed prior to CD4 engagement but do not otherwise contribute to neutralization breadth and potency against most primary virus strains. Triggering of the viral spike to reveal V3 epitopes may be required if V3 immunogens are to be components of an effective HIV-1 vaccine.
C1 [Davis, Katie L.; Kutsch, Olaf; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Bibollet-Ruche, Frederic; Li, Hui; Decker, Julie M.; Kutsch, Olaf; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Morris, Lynn] Natl Inst Communicable Dis, AIDS Virus Res Unit, Johannesburg, South Africa.
[Salomon, Aidy; Pinter, Abraham] Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Salomon, Aidy; Pinter, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
[Hoxie, James A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Shaw, GM (reprint author), Univ Alabama, Dept Med, 720 20th St S, Birmingham, AL 35294 USA.
EM gshaw@uab.edu
OI , Lynn/0000-0003-3961-7828
FU Bill and Melinda Gates Foundation [37874, 38619, 38631]; NIH [AI 67854,
AI 27767, AI 46238]
FX This work was supported by grants from the Bill and Melinda Gates
Foundation (37874, 38619, and 38631) and the NIH (AI 67854, AI 27767,
and AI 46238).
NR 108
TC 43
Z9 43
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 FEB 1
PY 2009
VL 83
IS 3
BP 1240
EP 1259
DI 10.1128/JVI.01743-08
PG 20
WC Virology
SC Virology
GA 392TR
UT WOS:000262325600008
PM 19019969
ER
PT J
AU Chen, Z
DeSalle, R
Schiffman, M
Herrero, R
Burk, RD
AF Chen, Zigui
DeSalle, Rob
Schiffman, Mark
Herrero, Rolando
Burk, Robert D.
TI Evolutionary Dynamics of Variant Genomes of Human Papillomavirus Types
18, 45, and 97
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID COMPLETE NUCLEOTIDE-SEQUENCE; GENITAL HUMAN-PAPILLOMAVIRUS; GRADE
CERVICAL LESIONS; VIRUS-POSITIVE WOMEN; AMINO-ACID SITES; DIVERSIFYING
SELECTION; WORLDWIDE PERSPECTIVE; PHYLOGENETIC ANALYSIS;
NATURAL-HISTORY; OVERLAPPING PCR
AB Human papillomavirus type 18 (HPV18) and HPV45 account for approximately 20% of all cervix cancers. We show that HPV18, HPV45, and the recently discovered HPV97 comprise a clade sharing a most recent common ancestor within HPV alpha 7 species. Variant lineages of these HPV types were classified by sequence analysis of the upstream regulatory region/E6 region among cervical samples from a population-based study in Costa Rica, and 27 representative genomes from each major variant lineage were sequenced. Nucleotide variation within HPV18 and HPV45 was 3.82% and 2.39%, respectively, and amino acid variation was 4.73% and 2.87%, respectively. Only 18 nucleotide variations, of which 10 were nonsynonymous, were identified among three HPV97 genomes. Full-genome comparisons revealed maximal diversity between HPV18 African and non-African variants (2.6% dissimilarity), whereas HPV18 Asian-American [E1 (AA)] and European (E2) variants were closely related ( less than 0.5% dissimilarity); HPV45 genomes had a maximal difference of 1.6% nucleotides. Using a Bayesian Markov chain Monte Carlo (MCMC) method, the divergence times of HPV18, -45, and -97 from their most recent common ancestors indicated that HPV18 diverged approximately 7.7 million years (Myr) ago, whereas HPV45 and HPV97 split off around 5.7 Myr ago, in a period encompassing the divergence of the great ape species. Variants within the HPV18/45/97 lineages were estimated to have diverged from their common ancestors in the genus Homo within the last 1 Myr (<0.7 Myr). To investigate the molecular basis of HPV18, HPV45, and HPV97 evolution, regression models of codon substitution were used to identify lineages and amino acid sites under selective pressure. The E5 open reading frame (ORF) of HPV18 and the E4 ORFs of HPV18, HPV45, and HPV18/45/97 had nonsynonymous/ synonymous substitution rate ratios (dN/dS) over 1 indicative of positive Darwinian selection. The L1 ORF of HPV18 genomes had an increased proportion of nonsynonymous substitutions (4.93%; average dN/dS ratio [M3] = 0.3356) compared to HPV45 (1.86%; M3 = 0.1268) and HPV16 (2.26%; M3 = 0.1330) L1 ORFs. In contrast, HPV18 and HPV16 genomes had similar amino acid substitution rates within the E1 ORF (2.89% and 3.24%, respectively), while HPV45 E1 was highly conserved (amino acid substitution rate was 0.77%). These data provide an evolutionary history of this medically important clade of HPVs and identify an unexpected divergence of the L1 gene of HPV18 that may have clinical implications for the long-term use of an L1-virus-like particle-based prophylactic vaccine.
C1 [Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
[DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.
[Herrero, Rolando] Costa Rica Fdn Hlth Sci, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Burk, Robert D.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womans Hlth, Bronx, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
RP Burk, RD (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM burk@aecom.yu.edu
RI Chen, Zigui/E-8490-2017
FU National Cancer Institute [CA78527]
FX This work was supported in part by Public Health Service award CA78527
from the National Cancer Institute. R. D. thanks the Louis and Dorothy
Cullman Program in Molecular Systematics at the American Museum of
Natural History for support.
NR 51
TC 45
Z9 48
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD FEB 1
PY 2009
VL 83
IS 3
BP 1443
EP 1455
DI 10.1128/JVI.02068-08
PG 13
WC Virology
SC Virology
GA 392TR
UT WOS:000262325600027
PM 19036820
ER
PT J
AU Mason, RD
Alcantara, S
Peut, V
Loh, L
Lifson, JD
De Rose, R
Kent, SJ
AF Mason, Rosemarie D.
Alcantara, Sheilajen
Peut, Viv
Loh, Liyen
Lifson, Jeffrey D.
De Rose, Robert
Kent, Stephen J.
TI Inactivated Simian Immunodeficiency Virus-Pulsed Autologous Fresh Blood
Cells as an Immunotherapy Strategy
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD8(+) T-CELLS; DENDRITIC CELLS; FUNCTIONAL IMPAIRMENT; PROTECTIVE
EFFICACY; VIRAL LOAD; VACCINE; RESPONSES; HIV; MACAQUES; INFECTION
AB Practical immunotherapies for human immunodeficiency virus infection are needed. We evaluated inactivated simian immunodeficiency virus (SIV) pulsed onto fresh peripheral blood mononuclear cells in 12 pigtail macaques with chronic SIV(mac251) infection for T-cell immunogenicity in a randomized cross-over design study. The immunotherapy was safe and convincingly induced high levels of SIV-specific CD4(+) T-cell responses ( mean, 5.9% +/- 1.3% of all CD4(+) T cells) and to a lesser extent SIV-specific CD8(+) T-cell responses (mean, 0.7% +/- 0.4%). Responses were primarily directed toward Gag and less frequently toward Env but not Pol or regulatory/accessory SIV proteins. T-cell responses against Gag were generally broad and polyfunctional, with a mean of 2.7 CD4(+) T-cell epitopes mapped per animal and more than half of the SIV Gag-specific CD4(+) T cells expressing three or more effector molecules. The immunogenicity was comparable to that found in previous studies of peptide-pulsed blood cells. Despite the high-level immunogenicity, no reduction in viral load was observed in the chronically viremic macaques. This contrasts with our studies of immunization with peptide- pulsed blood cells during early SIV infection in macaques. Future studies of inactivated virus-pulsed blood cell immunotherapy during early infection of patients receiving antiretroviral therapy are warranted.
C1 [Mason, Rosemarie D.; Alcantara, Sheilajen; Peut, Viv; Loh, Liyen; De Rose, Robert; Kent, Stephen J.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
[Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Natl Canc Inst, Frederick, MD 21792 USA.
RP Kent, SJ (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
EM skent@unimelb.edu.au
OI De Rose, Robert/0000-0003-4316-3910; Kent, Stephen/0000-0002-8539-4891
FU Australian Centre for HIV and Hepatitis Research; Canadian Institutes of
Health Research; Australian National Health and Medical Research
Council; National Cancer Institute; NIH [N01-CO-12400,
HHSN266200400088C]
FX This work was supported by the Australian Centre for HIV and Hepatitis
Research, the Canadian Institutes of Health Research, Australian
National Health and Medical Research Council grants, and by the National
Cancer Institute, NIH, under contracts N01-CO-12400 and
HHSN266200400088C (J.D.L.).
NR 34
TC 13
Z9 13
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 FEB 1
PY 2009
VL 83
IS 3
BP 1501
EP 1510
DI 10.1128/JVI.02119-08
PG 10
WC Virology
SC Virology
GA 392TR
UT WOS:000262325600033
PM 19019966
ER
PT J
AU Schowalter, RM
Chang, A
Robach, JG
Buchholz, UJ
Dutch, RE
AF Schowalter, Rachel M.
Chang, Andres
Robach, Jessica G.
Buchholz, Ursula J.
Dutch, Rebecca Ellis
TI Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues
and Importance in Entry
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; VESICULAR STOMATITIS-VIRUS;
CLATHRIN-MEDIATED ENDOCYTOSIS; PARAMYXOVIRUS MEMBRANE-FUSION; SMALL
HYDROPHOBIC SH; INFLUENZA HEMAGGLUTININ; F-PROTEIN; VERO CELLS;
PARAINFLUENZA VIRUS-5; ENVELOPE GLYCOPROTEIN
AB Human metapneumovirus (HMPV) is a significant respiratory pathogen classified in the Pneumovirinae subfamily of the paramyxovirus family. Recently, we demonstrated that HMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. In the present study, we examined the potential role of histidine protonation in HMPV F fusion and investigated the role of low pH in HMPV viral entry. Mutagenesis of the three ectodomain histidine residues of the HMPV F protein demonstrated that the mutation of a histidine in the heptad repeat B linker domain (H435) ablated fusion activity without altering cell surface expression or proteolytic processing significantly. Modeling of the HMPV F protein revealed several basic residues surrounding this histidine residue, and the mutation of these residues also reduced fusion activity. These results suggest that electrostatic repulsion in the heptad repeat B linker region may contribute to the triggering of HMPV F. In addition, we examined the effect of inhibitors of endosomal acidification or endocytosis on the entry of a recombinant green fluorescent protein-expressing HMPV. Interestingly, chemicals that raise the pH of endocytic vesicles resulted in a 30 to 50% decrease in HMPV infection, while the inhibitors of endocytosis reduced infection by as much as 90%. These data suggest that HMPV utilizes an endocytic entry mechanism, in contrast to what has been hypothesized for most paramyxoviruses. In addition, our results indicate that HMPV uses the low pH of the endocytic pathway to enhance infectivity, though the role of low pH likely differs from classically described mechanisms.
C1 [Schowalter, Rachel M.; Chang, Andres; Dutch, Rebecca Ellis] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
[Robach, Jessica G.] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
[Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Dutch, RE (reprint author), Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Biomed Biol Sci Res Bldg,741 South Limestone, Lexington, KY 40536 USA.
EM rdutc2@uky.edu
FU Great Rivers affiliate of the American Heart Association [0715355B];
March of Dimes; National Institutes of Health. [1R21AI074783-01]
FX This study was supported by predoctoral fellowship 0715355B from the
Great Rivers affiliate of the American Heart Association, a research
grant from the March of Dimes, and research grant 1R21AI074783-01 from
the National Institutes of Health.
NR 67
TC 50
Z9 54
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 FEB 1
PY 2009
VL 83
IS 3
BP 1511
EP 1522
DI 10.1128/JVI.01381-08
PG 12
WC Virology
SC Virology
GA 392TR
UT WOS:000262325600034
PM 19036821
ER
PT J
AU Gill, JM
Szanton, S
Taylor, TJ
Page, GG
Campbell, JC
AF Gill, Jessica M.
Szanton, S.
Taylor, T. J.
Page, G. G.
Campbell, J. C.
TI Medical Conditions and Symptoms Associated with Posttraumatic Stress
Disorder in Low-Income Urban Women
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID INTIMATE PARTNER VIOLENCE; ADMINISTERED PTSD SCALE; PRIMARY-CARE
PATIENTS; SELF-REPORTED HEALTH; AFRICAN-AMERICANS; ADOLESCENT GIRLS;
PHYSICAL HEALTH; SUBSTANCE-ABUSE; TRAUMA EXPOSURE; MENTAL-HEALTH
AB Background: Epidemiological studies have consistently reported rates of posttraumatic stress disorder (PTSD) in women that are twice that of men. In men and women, PTSD has been associated with comorbid medical conditions, medical symptoms and lower self-rating of health. In low-income urban women, rates of PTSD are even more elevated than in suburban women and may be related to observed health disparities.
Methods: In this study, 250 women seeking healthcare at an urban clinic were interviewed for a PTSD diagnosis, major depressive disorder (MDD), the experience of traumatic events, the experience of current and past common medical conditions and symptoms, and subjective rating of health. A chart review was used to assess healthcare use in the past year.
Results: More current (5.2 vs. 3.8, p < 0.05) and past medical conditions (4.6 vs. 3.3, p < 0.05) were reported by women with a lifetime history of PTSD than by women without this history, after controlling for demographics and current depression. Women with lifetime PTSD also had more annual clinic appointments (5.9 vs. 3.8 p < 0.03) and were 2.4 times (p < 0.05) more likely to report lower appraisal of their physical health.
Conclusions: These findings suggest that urban health-seeking women with PTSD experience health impairments that may cause increased morbidity and that healthcare providers should consider the health ramifications of PTSD when providing medical care to women.
C1 [Gill, Jessica M.; Taylor, T. J.] Natl Inst Nursing Res, NIH, Bethesda, MD USA.
[Szanton, S.; Page, G. G.; Campbell, J. C.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
RP Gill, JM (reprint author), Natl Inst Natl Certificate, NIH, 10 Ctr Dr,10-CRC 2-1339, Bethesda, MD 20892 USA.
EM gillj@mail.nih.gov
FU National Institutes of Health, National Institute of Nursing Research
(NINR) [8326927]; Individual National Research Service Award (NRSA)
funded through NINR [F31 NR009166]; Institutional Training grant funded
through NINR [T32 NR 07968]; Fear Shanon Davies Memorial Grant
FX Funding was provided by the National Institutes of Health, National
Institute of Nursing Research (NINR) postdoctoral fellowship 8326927;
Individual National Research Service Award (NRSA) F31 NR009166 funded
through NINR; Institutional Training grant funded through NINR T32 NR
07968; Health Disparities in Underserved Populations; and The Freedom
from Fear Shanon Davies Memorial Grant.
NR 51
TC 10
Z9 10
U1 4
U2 7
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 FEB
PY 2009
VL 18
IS 2
BP 261
EP 267
DI 10.1089/jwh.2008.0914
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 402HE
UT WOS:000263004000017
PM 19183098
ER
PT J
AU Sierra, F
AF Sierra, Felipe
TI Biology of Aging Summit Report Foreword
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
C1 NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA.
RP Sierra, F (reprint author), NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA.
EM sierraf@nia.nih.gov
NR 0
TC 6
Z9 6
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 FEB
PY 2009
VL 64
IS 2
BP 155
EP 156
DI 10.1093/gerona/gln069
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 419AB
UT WOS:000264190400001
PM 19228781
ER
PT J
AU Morrell, CH
Brant, LJ
Ferrucci, L
AF Morrell, Christopher H.
Brant, Larry J.
Ferrucci, Luigi
TI Model Choice Can Obscure Results in Longitudinal Studies
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Mixed-effects models; Multilevel modeling; Observational study;
Recruitment bias; Regression
ID MIXED-EFFECTS MODELS; OLDER MEXICAN-AMERICANS; REGRESSION-MODELS;
SELECTION BIAS; HIP FRACTURE; DECLINE; DISEASE; WOMEN
AB Background. This article examines how different parameterizations of age and time in modeling observational longitudinal data can affect results.
Methods. When individuals of different ages at study entry are considered, it becomes necessary to distinguish between longitudinal and cross-sectional differences to overcome possible selection biases.
Results. Various models were fitted using data from longitudinal studies with participants with different ages and different follow-up lengths. Decomposing age into two components-age at entry into the study (first age) and the longitudinal follow-up (time) compared with considering age alone-leads to different conclusions.
Conclusions. In general, models using both first age and time terms performed better, and these terms are usually necessary to correctly analyze longitudinal data
C1 [Morrell, Christopher H.; Brant, Larry J.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Harbor Hosp, Baltimore, MD 21224 USA.
RP Brant, LJ (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM larry_brant@nih.gov
FU National Institutes of Health; National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging
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U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD FEB
PY 2009
VL 64
IS 2
BP 215
EP 222
DI 10.1093/gerona/gln024
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 419AB
UT WOS:000264190400017
PM 19196902
ER
PT J
AU Vasunilashorn, S
Coppin, AK
Patel, KV
Lauretani, F
Ferrucci, L
Bandinelli, S
Guralnik, JM
AF Vasunilashorn, Sarinnapha
Coppin, Antonia K.
Patel, Kushang V.
Lauretani, Fulvio
Ferrucci, Luigi
Bandinelli, Stefania
Guralnik, Jack M.
TI Use of the Short Physical Performance Battery Score to Predict Loss of
Ability to Walk 400 Meters: Analysis From the InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Mobility; 400 m walk; Incidence of disability; Functional limitation;
Aging
ID LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; MOBILITY LIMITATION; SUBSEQUENT
DISABILITY; FUNCTIONAL MOBILITY; OBJECTIVE-MEASURE; ELDERLY PERSONS;
RISK-FACTORS; TAI-CHI; EXERCISE
AB Background. Early detection of mobility limitations remains an important goal for preventing mobility disability. The purpose of this study was to examine the association between the Short Physical Performance Battery (SPPB) and the loss of ability to walk 400 m, an objectively assessed mobility outcome increasingly used in clinical trials.
Methods. The study sample consisted of 542 adults from the InCHIANTI ("Invecchiare in Chianti," aging in Chianti area) study aged 65 and older, who completed the 400 m walk at baseline and had evaluations on the SPPB and 400 m walk at baseline and 3-year follow-up. Multiple logistic regression models were used to determine whether SPPB scores predict the loss of ability to walk 400 m at follow-up among persons able to walk 400 m at baseline.
Results. The 3-year incidence of failing the 400 m walk was 15.5%. After adjusting for age, sex, education, body mass index, Mini-Mental State Examination, number of medical conditions, and 400 m walk gait speed at baseline, SPPB score was significantly associated with loss of ability to walk 400 m after 3 years. Participants with SPPB scores of 10 or lower at baseline had significantly higher odds of mobility disability at follow-up ( odds ratio [ OR] = 3.38, 95% confidence interval [ CI]: 1.32-8.65) compared with those who scored 12, with a graded response across the range of SPPB scores ( OR = 26.93, 95% CI: 7.51-96.50; OR = 7.67, 95% CI: 2.26-26.04; OR = 8.28, 95% CI: 3.32-20.67 for SPPB = 7, SPPB 8, and SPPB 9, respectively).
Conclusions. The SPPB strongly predicts loss of ability to walk 400 m. Thus, using the SPPB to identify older persons at high risk of lower body functional limitations seems a valid means of recognizing individuals who would benefit most from preventive interventions.
C1 [Vasunilashorn, Sarinnapha] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Lauretani, Fulvio] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Lauretani, Fulvio] Tuscany Hlth Reg Agcy, Florence, Italy.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
RP Vasunilashorn, S (reprint author), Univ So Calif, Davis Sch Gerontol, 3715 McClintock Ave, Los Angeles, CA 90089 USA.
EM vasunila@usc.edu
RI Lauretani, Fulvio/K-5115-2016
OI Lauretani, Fulvio/0000-0002-5287-9972
FU Italian Ministry of Health [ICS 110.1/RS97.71]; National Institutes of
Health (NIH); National Institute on Aging [N01-AG-1-2111,
T32AG000037-27]
FX The InCHIANTI study was supported as a "targeted project" (ICS 110.1/
RS97.71) by the Italian Ministry of Health and in part by the Intramural
Research Program of the National Institutes of Health (NIH), National
Institute on Aging ( contract N01-AG-1-2111). This research was
supported in part by grants from the National Institute on Aging
(T32AG000037-27) and in part by the Intramural Research Program,
National Institute on Aging, NIH. Eileen Crimmins and Merril Silverstein
provided helpful suggestions on previous drafts of the article.
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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 FEB
PY 2009
VL 64
IS 2
BP 223
EP 229
DI 10.1093/gerona/gln022
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 419AB
UT WOS:000264190400018
PM 19182232
ER
PT J
AU Viljanen, A
Kaprio, J
Pyykko, I
Sorri, M
Pajala, S
Kauppinen, M
Koskenvuo, M
Rantanen, T
AF Viljanen, Anne
Kaprio, Jaakko
Pyykko, Ilmari
Sorri, Martti
Pajala, Satu
Kauppinen, Markku
Koskenvuo, Markku
Rantanen, Taina
TI Hearing as a Predictor of Falls and Postural Balance in Older Female
Twins
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Hearing; Postural balance; Fall; Twin study; Heritability; Aging
ID ENVIRONMENTAL-INFLUENCES; ELDERLY-PEOPLE; WOMEN; RISK; PERFORMANCE;
DYSFUNCTION; POPULATION; NEED; GAIT
AB Background. The purpose of the present study was to examine, first, whether hearing acuity predicts falls and whether the potential association is explained by postural balance and, second, to examine whether shared genetic or environmental effects underlie these associations.
Methods. Hearing was measured using a clinical audiometer as a part of the Finnish Twin Study on Aging in 103 monozygotic and 114 dizygotic female twin pairs aged 63-76 years. Postural balance was indicated as a center of pressure (COP) movement in semitandem stance, and participants filled in a fall-calendar daily for an average of 345 days after the baseline.
Results. Mean hearing acuity (better ear hearing threshold level at 0.5-4 kHz) was 21 dB (standard deviation [SD] 12). Means of the COP velocity moment for the best to the poorest hearing quartiles increased linearly from 40.7 mm(2)/s ( SD 24.4) to 52.8 mm(2)/s (SD 32.0) (p value for the trend = .003). Altogether 199 participants reported 437 falls. Age-adjusted incidence rate ratios (IRRs) for falls, with the best hearing quartile as a reference, were 1.2 (95% confidence interval [CI] = 0.4-3.8) in the second, 4.1 (95% CI = 1.1-15.6) in the third, and 3.4 (95% CI = 1.0-11.4) in the poorest hearing quartiles. Adjustment for COP velocity moment decreased IRRs markedly. Twin analyses showed that the association between hearing acuity and postural balance was not explained by genetic factors in common for these traits.
Conclusion. People with poor hearing acuity have a higher risk for falls, which is partially explained by their poorer postural control. Auditory information about environment may be important for safe mobility.
C1 [Viljanen, Anne; Kauppinen, Markku; Rantanen, Taina] Univ Jyvaskyla, Finnish Ctr Interdisciplinary Gerontol, Dept Hlth Sci, FIN-40014 Jyvaskyla, Finland.
[Kaprio, Jaakko; Koskenvuo, Markku] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland.
[Kaprio, Jaakko] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland.
[Pyykko, Ilmari] Tampere Univ Hosp, Dept Otorhinolaryngol & Head & Neck Surg, Tampere, Finland.
[Sorri, Martti] Univ Oulu, Dept Otorhinolaryngol, Oulu, Finland.
[Pajala, Satu] NIA, LEBD, NIH, Bethesda, MD 20892 USA.
RP Viljanen, A (reprint author), Univ Jyvaskyla, Finnish Ctr Interdisciplinary Gerontol, Dept Hlth Sci, POB 35 Viveca, FIN-40014 Jyvaskyla, Finland.
EM anne.viljanen@sport.jyu.fi
RI Kaprio, Jaakko/A-1820-2008; Rantanen, Taina/O-6579-2016;
OI Rantanen, Taina/0000-0002-1604-1945; Viljanen, Anne/0000-0002-8428-3604;
Kaprio, Jaakko/0000-0002-3716-2455
FU Academy of Finland; Ministry of Education, Finland; GENOMEUTWIN; EU
[QLG2-CT-2002-01254]
FX This study was funded from grants by the Academy of Finland, the
Ministry of Education, Finland, and the GENOMEUTWIN project (EU grant
no. QLG2-CT-2002-01254). S. P. was supported by the Intramural Research
Program of the National Institutes of Health, National Institute on
Aging. We are indebted to all the participants for their commitment to
the study.
NR 35
TC 53
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U1 0
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 FEB
PY 2009
VL 64
IS 2
BP 312
EP 317
DI 10.1093/gerona/gln015
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 419AB
UT WOS:000264190400031
PM 19182227
ER
PT J
AU Moeller, HB
Knepper, MA
Fenton, RA
AF Moeller, Hanne B.
Knepper, Mark A.
Fenton, Robert A.
TI Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane
of collecting duct principal cells
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE phosphorylation; vasopressin; endocytosis; exocytosis;
immunohistochemistry; aquaporin water channel
ID WATER CHANNEL; VASOPRESSIN TREATMENT; EPITHELIAL-CELLS; PLASMA-MEMBRANE;
RAT-KIDNEY; AQP2; TRAFFICKING; EXPRESSION; PERMEABILITY; ENDOCYTOSIS
AB Trafficking of the water channel aquaporin-2 to the apical plasma membrane of the collecting duct is mediated by arginine vasopressin, rendering the cell permeable to water. We recently identified a novel form of aquaporin-2 that is phosphorylated at serine-269 (pS269-AQP2). Using antibodies specific for this form of the water channel, we detected rat and mouse pS269-AQP2 in the connecting tubule and throughout the collecting duct system. Using confocal immunofluorescence microscopy with organelle-specific markers and immunogold electron microscopy, we found that pS269-AQP2 was found only on the apical plasma membrane of principal cells. In vasopressin-deficient Brattleboro rats, pS269-AQP2 was undetectable but dramatically increased in abundance after these rats were treated with [deamino-Cys-1, d-Arg8] vasopressin (dDAVP). This increase occurred only at the apical plasma membrane, even after long-term dDAVP treatment. Following dDAVP there was a time-dependent redistribution of total aquaporin-2 from predominantly intracellular vesicles to the apical plasma membrane, clathrin-coated vesicles, early endosomal compartments, and lysosomes. However, pS269-AQP2 was found only on the apical plasma membrane at any time. Our results show that S269 phosphorylated aquaporin-2 is exclusively associated with the apical plasma membrane, where it escapes endocytosis to remain at the cell surface.
C1 [Moeller, Hanne B.; Fenton, Robert A.] Univ Aarhus, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark.
[Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Fenton, RA (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Bldg 1233, DK-8000 Aarhus, Denmark.
EM rofe@ana.au.dk
FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21, Z01 HL001285-22, ZIA
HL001285-23, ZIA HL001285-24]; NHLBI NIH HHS [Z01 HL001285,
Z01-HL001285]
NR 27
TC 54
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U1 1
U2 1
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 FEB
PY 2009
VL 75
IS 3
BP 295
EP 303
DI 10.1038/ki.2008.505
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 394YP
UT WOS:000262489400009
PM 18843259
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD USA.
[Gipson, Chester] USDA, APHIS, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD FEB
PY 2009
VL 38
IS 2
BP 47
EP 47
DI 10.1038/laban0209-47
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 406KO
UT WOS:000263294400005
PM 19165188
ER
PT J
AU Schnabel, RB
Sullivan, LM
Levy, D
Pencina, M
Massaro, JM
D'Agostino, RB
Newton-Cheh, C
Yamamoto, JF
Magnani, JW
Tadros, TM
Kannel, WB
Wang, TJ
Ellinor, PT
Wolf, PA
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Sullivan, Lisa M.
Levy, Daniel
Pencina, Michael
Massaro, Joseph M.
D'Agostino, Ralph B., Sr.
Newton-Cheh, Christopher
Yamamoto, Jennifer F.
Magnani, Jared W.
Tadros, Thomas M.
Kannel, William B.
Wang, Thomas J.
Ellinor, Patrick T.
Wolf, Philip A.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Development of a risk score for atrial fibrillation (Framingham Heart
Study): a community-based cohort study
SO LANCET
LA English
DT Article
ID OLDER-ADULTS; PHYSICAL-ACTIVITY; PREVENTION; OBESITY; HEALTH;
METAANALYSIS; PREVALENCE; PREDICTION; MORTALITY; SURVIVAL
AB Background Atrial fibrillation contributes to substantial increases in morbidity and mortality. We aimed to develop a risk score to predict individuals' absolute risk of developing the condition, and to provide a framework for researchers to assess new risk markers.
Methods We assessed 4764 participants in the Framingham Heart Study from 8044 examinations (55% women, 45-95 years of age) undertaken between June, 1968, and September, 1987. Thereafter, participants were monitored for the first event of atrial fibrillation for a maximum of 10 years. Multivariable Cox regression identified clinical risk factors associated with development of atrial fibrillation in 10 years. Secondary analyses incorporated routine echocardiographic measurements (5152 participants, 7156 examinations) to reclassify the risk of atrial fibrillation and to assess whether these measurements improved risk prediction.
Findings 457 (10%) of the 4764 participants developed atrial fibrillation. Age, sex, body-mass index, systolic blood pressure, treatment for hypertension, PR interval, clinically significant cardiac murmur, and heart failure were associated with atrial fibrillation and incorporated in a risk score (p<0.05, except body-mass index p=0.08), clinical model C statistic 0.78 (95% Cl 0.76-0.80). Risk of atrial fibrillation in 10 years varied with age: more than 15% risk was recorded in 53 (1%) participants younger than 65 years, compared with 783 (27%) older than 65 years. Additional incorporation of echocardiographic measurements to enhance the risk prediction model only slightly improved the C statistic from 0.78 (95% CI 0.75-0.80) to 0.79 (0.77-0.82), p=0.005. Echocardiographic measurements did not improve risk reclassification (p=0.18).
Interpretation From clinical factors readily accessible in primary care, our risk score could help to identify risk of atrial fibrillation for individuals in the community; assess technologies or markers for improvement of risk prediction, and target high-risk individuals for preventive measures.
C1 [Benjamin, Emelia J.] Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA 01702 USA.
[Sullivan, Lisa M.; Pencina, Michael; Massaro, Joseph M.; Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Kannel, William B.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Dept Med, Boston, MA 02118 USA.
[Levy, Daniel; Massaro, Joseph M.; Tadros, Thomas M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Evans Mem Dept Med, Boston, MA 02118 USA.
[Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Evans Mem Dept Med, Boston, MA 02118 USA.
[Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.
RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM emelia@bu.edu
RI Schnabel, Renate/F-6527-2014;
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU US National Institutes of Health (NIH)/National Heart, Lung and Blood
Institute [N01-HC-25195]; NIH [HL076784, AG028321, AG029451, HL092577,
HL080124, HL077477, HL71039, HL093328, R01 NS 17950, 2K24 HL04334];
Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN
1149/1-1]; Doris Duke Charitable Foundation Clinical Scientist
Development Award [HL080025]; Burroughs Wellcome Fund Career Award for
Medical Scientists
FX Supported by US National Institutes of Health (NIH)/National Heart, Lung
and Blood Institute contract N01-HC-25195 and NIH grants HL076784,
AG028321. and AG029451 (E)B) HL092577 (EJB, PTE); HL080124, HL077477,
HL71039, and HL093328 (RSV); R01 NS 17950 (PAW). NIH Research Career
Award 2K24 HL04334 (RSV); Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship SCHN 1149/1-1 (RBS); HL080025,
Doris Duke Charitable Foundation Clinical Scientist Development Award,
and Burroughs Wellcome Fund Career Award for Medical Scientists (CN-C).
NR 35
TC 395
Z9 408
U1 3
U2 25
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 FEB-MAR
PY 2009
VL 373
IS 9665
BP 739
EP 745
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 412LD
UT WOS:000263725400033
PM 19249635
ER
PT J
AU Hacke, W
Furlan, AJ
Al-Rawi, Y
Davalos, A
Fiebach, JB
Gruber, F
Kaste, M
Lipka, LJ
Pedraza, S
Ringleb, PA
Rowley, HA
Schneider, D
Schwamm, LH
Leal, JS
Sooehngen, M
Teal, PA
Wilhelm-Ogunbiyi, K
Wintermark, M
Warach, S
AF Hacke, Werner
Furlan, Anthony J.
Al-Rawi, Yasir
Davalos, Antoni
Fiebach, Jochen B.
Gruber, Franz
Kaste, Markku
Lipka, Leslie J.
Pedraza, Salvador
Ringleb, Peter A.
Rowley, Howard A.
Schneider, Dietmar
Schwamm, Lee H.
Leal, Joaquin Serena
Soehngen, Mariola
Teal, Phil A.
Wilhelm-Ogunbiyi, Karin
Wintermark, Max
Warach, Steven
TI Intravenous desmoteplase in patients with acute ischaemic stroke
selected by MRI perfusion-diffusion weighted imaging or perfusion CT
(DIAS-2): a prospective, randomised, double-blind, placebo-controlled
study
SO LANCET NEUROLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE HEMISPHERIC STROKE;
CONTROLLED-TRIAL; ALTEPLASE; THROMBOLYSIS; ECASS; ATLANTIS; ONSET
AB Background Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI).
Methods In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (11:1) to 90 mu g/kg desmoteplase, 125 mu g/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852.
Findings Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 mu g/kg desmoteplase; 66 received 125 mu g/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 mu g/kg desmoteplase, 36% (24 of 66) for 125 mu g/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 mu g/kg desmoteplase 14.0% (0.5 cm(3)); 125 mu g/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 mu g/kg desmoteplase, 4.5% (3 of 66) for 125 mu g/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% 13 of 571 for 90 mu g/kg desmoteplase; 21% [14 of 66] for 125 mu g/kg desmoteplase; and 6% [4 of 63] for placebo).
Interpretation The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. ne high response rate in the placebo group could be explained by the mild strokes recorded (low base-line NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase.
C1 [Hacke, Werner; Ringleb, Peter A.] Univ Heidelberg, Dept Neurol, D-69120 Heidelberg, Germany.
[Furlan, Anthony J.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Neurol Inst, Dept Neurol, Cleveland, OH USA.
[Al-Rawi, Yasir] MEGA Pharma Solut FZE, Rak, U Arab Emirates.
[Davalos, Antoni] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Dept Neurosci, Barcelona, Spain.
[Fiebach, Jochen B.] Dept Neurol, Berlin, Germany.
[Fiebach, Jochen B.] Berlin Neuroimaging Ctr, Berlin, Germany.
[Gruber, Franz] Gen Hosp Linz, Dept Neurol & Psychiat, Neuro ICU, Linz, Austria.
[Kaste, Markku] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
[Lipka, Leslie J.] Forest Labs Inc, Jersey City, NJ USA.
[Leal, Joaquin Serena] Hosp Univ Dr Josep Trueta Girona, Dept Neurol, Girona, Spain.
[Pedraza, Salvador] Hosp Univ Dr Josep Trueta Girona, Dept Radiol, Girona, Spain.
[Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Schneider, Dietmar] Univ Leipzig, Neurol ICU, Leipzig, Germany.
[Schneider, Dietmar] Univ Leipzig, Stroke Unit, Leipzig, Germany.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Soehngen, Mariola; Wilhelm-Ogunbiyi, Karin] PAION AG, Aachen, Germany.
[Ringleb, Peter A.] Univ British Columbia, Vancouver Gen Hosp, Div Neurol, Vancouver, BC V5Z 1M9, Canada.
[Wintermark, Max] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Warach, Steven] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Hacke, W (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
EM werner.hacke@med.uni-heidelberg.de
OI Ringleb, Peter/0000-0002-5473-8671; Fiebach, Jochen
B./0000-0002-7936-6958; Schwamm, Lee/0000-0003-0592-9145; Wintermark,
Max/0000-0002-6726-3951; Kaste, Markku/0000-0001-6557-6412
FU PAION Deutschland GmbH; Forest Laboratories
FX Funding PAION Deutschland GmbH; Forest Laboratories.
NR 18
TC 316
Z9 330
U1 0
U2 23
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 FEB
PY 2009
VL 8
IS 2
BP 141
EP 150
DI 10.1016/S1474-4422(08)70267-9
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 398SO
UT WOS:000262752000012
PM 19097942
ER
PT J
AU Greenberg, SM
Vernooij, MW
Cordonnier, C
Viswanathan, A
Salman, RAS
Warach, S
Launer, LJ
Van Buchem, MA
Breteler, MMB
AF Greenberg, Steven M.
Vernooij, Meike W.
Cordonnier, Charlotte
Viswanathan, Anand
Salman, Rustorn Al-Shahi
Warach, Steven
Launer, Lenore J.
Van Buchem, Mark A.
Breteler, Monique M. B.
CA Microbleed Study Grp
TI Cerebral microbleeds: a guide to detection and interpretation
SO LANCET NEUROLOGY
LA English
DT Review
ID T2-ASTERISK-WEIGHTED MR-IMAGES; GRADIENT-ECHO MRI; INTRACEREBRAL
HEMORRHAGE; AMYLOID ANGIOPATHY; ASYMPTOMATIC MICROBLEEDS; INTRACRANIAL
HEMORRHAGE; CAVERNOUS MALFORMATIONS; HEMOSIDERIN SPOTS; LOBAR
HEMORRHAGE; RISK-FACTORS
AB Cerebral microbleeds (CMBs) are increasingly recognised neuroimaging findings in individuals with cerebrovascular disease and dementia, and in normal ageing. There has been substantial progress in the understanding of CMBs in recent years, particularly in the development of newer MRI methods for the detection of CMBs and the application of these techniques to population-based samples of elderly people. In this Review, we focus on these recent developments and their effects on two main questions: how CMBs are detected, and how CMBs should be interpreted. The number of CMBs detected depends on MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and image post-processing, emphasising the importance of taking into account MRI technique in the interpretation of study results. Recent investigations with sensitive MRI techniques have indicated a high prevalence of CMBs in community-dwelling elderly people. We propose a procedural guide for identification of CMBs and suggest possible future approaches for elucidating the role of these common lesions as markers for, and contributors to, small-vessel brain disease.
C1 [Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Vernooij, Meike W.] Univ Med Ctr, Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Vernooij, Meike W.; Breteler, Monique M. B.] Univ Med Ctr, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Cordonnier, Charlotte] Lille Univ Hosp, Dept Neurol, Stroke Dept, Lille, France.
[Salman, Rustorn Al-Shahi] Univ Edinburgh, Western Gen Hosp, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Warach, Steven] Natl Inst Neurol Disorders & Stroke, Stroke Branch, Bethesda, MD USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Biometry & Demog, Bethesda, MD 20892 USA.
[Van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM sgreenberg@partners.org
RI Breteler, Monique /J-5058-2014; Vernooij, Meike/E-4061-2016; Gurol,
Edip/J-2279-2014;
OI Gurol, Edip/0000-0002-2169-4457; Al-Shahi Salman,
Rustam/0000-0002-2108-9222
FU sundry research funds; Massachusetts General Hospital Hemorrhagic Stroke
Research Program
FX Other members of the Microbleed Study Group who participated in the
Cerebral Microbleeds: Detection and Definition conference and
contributed valuable discussions and criticisms for this paper were M A
Ikram, M J Bos, M M F Poets (Rotterdam, Netherlands), I van der Grond
(Leiden, Netherlands), M E Gurol, and R N K Nandigam (Boston, USA). The
conference was held by the Microbleed Study Group on April 12, 2008 in
Chicago, USA and was supported by sundry research funds provided by
individual donors to the Massachusetts General Hospital Hemorrhagic
Stroke Research Program without commercial interests or contributions
from industry.
NR 71
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Z9 561
U1 6
U2 68
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 FEB
PY 2009
VL 8
IS 2
BP 165
EP 174
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 398SO
UT WOS:000262752000015
PM 19161908
ER
PT J
AU Dierov, J
Sanchez, PV
Burke, BA
Padilla-Nash, H
Putt, ME
Ried, T
Carroll, M
AF Dierov, J.
Sanchez, P. V.
Burke, B. A.
Padilla-Nash, H.
Putt, M. E.
Ried, T.
Carroll, M.
TI BCR/ABL induces chromosomal instability after genotoxic stress and
alters the cell death threshold
SO LEUKEMIA
LA English
DT Article
DE BCR/ABL; chronic myeloid leukemia; etoposide; spectral karyotyping
(SKY); genomic instability
ID CHRONIC MYELOID-LEUKEMIA; DOUBLE-STRAND BREAKS; BCR-ABL;
HEMATOPOIETIC-CELLS; CLONAL EVOLUTION; TYROSINE KINASE; DNA-DAMAGE;
EXPRESSION; APOPTOSIS; ABERRATIONS
AB Earlier reports have suggested that the BCR/ABL oncogene, associated with chronic myeloid leukemia, induces a mutator phenotype; however, it is unclear whether this leads to long-term changes in chromosomes and whether the phenotype is found in primary chronic myelogeneous leukemia (CML) cells. We have addressed both these issues. BCR/ABL-expressing cell lines show an increase in DNA breaks after treatment with etoposide as compared to control cells. However, although BCR/ABL-expressing cell lines have an equivalent cell survival, they have an increase in chromosomal translocations after DNA repair as compared to control cells. This demonstrates that BCR/ABL expression decreases the fidelity of DNA repair. To see whether this is true in primary CML samples, normal CD34+ progenitor cells and CML progenitor cells were treated with etoposide. CML progenitor cells have equivalent survival but have an increase in DNA double-strand breaks (DSBs). Spectral karyotyping demonstrates new chromosomal translocations in CML cells, but not normal progenitor cells, consistent with error-prone DNA repair. Taken together, these data demonstrate that BCR/ABL enhances the accumulation of DSBs and alters the apoptotic threshold in CML leading to error-prone DNA repair.
C1 [Dierov, J.; Sanchez, P. V.; Burke, B. A.; Carroll, M.] Univ Penn, Div Hematol & Oncol, Dept Med, Philadelphia, PA 19104 USA.
[Padilla-Nash, H.; Ried, T.] NCI, Sect Canc Gen, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Putt, M. E.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Carroll, M (reprint author), Univ Penn, Div Hematol & Oncol, Dept Med, BRB 2-3 Room 708,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM carroll2@mail.med.upenn.edu
FU Leukemia Lymphoma Society; NCI [R01CA100885]; National Institutes of
Health, National Cancer Institute, Center for Cancer Research
FX MC is a Clinical Scholar of the Leukemia Lymphoma Society and is
supported by NCI R01CA100885. This research was supported (in part) by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. We thank Tomasz
Skorski and colleagues for sharing data prior to publication. JD, PVS,
BAB and HP-N performed experiments. MEP performed statistical analysis.
TR provided reagents and expertise. MC supervised the experiments and
wrote the papers.
NR 29
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2009
VL 23
IS 2
BP 279
EP 286
DI 10.1038/leu.2008.308
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 406RJ
UT WOS:000263312300008
PM 19020542
ER
PT J
AU Ullmannova-Benson, V
Guan, M
Zhou, X
Tripathi, V
Yang, XY
Zimonjic, DB
Popescu, NC
AF Ullmannova-Benson, V.
Guan, M.
Zhou, X.
Tripathi, V.
Yang, X-Y
Zimonjic, D. B.
Popescu, N. C.
TI DLC1 tumor suppressor gene inhibits migration and invasion of multiple
myeloma cells through RhoA GTPase pathway
SO LEUKEMIA
LA English
DT Article
DE multiple myeloma; DLC1; tumor suppressor gene; promoter methylation;
migration; invasion
ID HEPATOCELLULAR-CARCINOMA; ACTIVATING PROTEIN; PROMOTER HYPERMETHYLATION;
PROSTATE-CANCER; METHYLATION; METASTASIS; EXPRESSION; PATHOGENESIS;
ASSOCIATION; PROFILES
AB DLC1 (deleted in liver cancer 1), a tumor suppressor gene that encodes a RhoGTPase-activating protein, is recurrently downregulated or silenced in various solid tumors and hematological malignancies because of epigenetic modifications or genomic deletion. Here, we identified DLC1 promoter hypermethylation in 43 out of 44 multiple myeloma (MM) cell lines, which resulted in downregulation or silencing of DLC1 in 41 samples. High frequency of tumor-specific methylation and attenuation or silencing of DLC1 expression could serve as an independent diagnostic marker for MM. Combined treatment with demethylating and acetylating agents significantly elevated the expression of DLC1 and suppressed MM cell proliferation. Two cell lines exhibiting complete promoter methylation and the absence of DLC1 expression were transduced by an adenoviral vector containing DLC1 cDNA. In both cell lines, the reexpression of DLC1 inhibited myeloma cell invasion and migration, reduced RhoA activity and resulted in the reorganization of actin cytoskeleton. These results provide the first evidence for the antiproliferative effect of DLC1 in a hematological cancer and implicate RhoA pathway in suppression of MM migration and invasion. Given the myeloma cells sensitivity to the reactivation of DLC1 function, the potential for molecular targeted therapy of DLC1-mediated pathways as well as epigenetic therapies hold prospects.
C1 [Ullmannova-Benson, V.; Guan, M.; Zhou, X.; Tripathi, V.; Yang, X-Y; Zimonjic, D. B.; Popescu, N. C.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Bldg 37,Room 4128,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA.
EM popescun@mail.nih.gov
RI yang, xuyu/D-1414-2012; Benson, Veronika/D-9942-2014
OI Benson, Veronika/0000-0003-4770-9909
FU National Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, NIH. We thank Dr Michael Kuehl (Center for
Cancer Research, National Cancer Institute, Bethesda, MD, USA) for
providing DNA and RNA samples isolated from multiple myeloma cell lines,
critical reading of the manuscript and most helpful suggestions. We also
thank to Dr Sheng Chen for kindly providing plasma cells samples from
healthy donors.
NR 49
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U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2009
VL 23
IS 2
BP 383
EP 390
DI 10.1038/leu.2008.285
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 406RJ
UT WOS:000263312300020
PM 18923442
ER
PT J
AU Lee, KM
Ward, MH
Han, S
Ahn, HS
Kang, HJ
Choi, HS
Shin, HY
Koo, HH
Seo, JJ
Choi, JE
Ahn, YO
Kang, D
AF Lee, Kyoun -Mu
Ward, Mary H.
Han, Sohee
Ahn, Hyo Seop
Kang, Hyoung Jin
Choi, Hyung Soo
Shin, Hee Young
Koo, Hong-Hoe
Seo, Jong-Jin
Choi, Ji-Eun
Ahn, Yoon-Ok
Kang, Daehee
TI Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia
risk
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Childhood leukemia; Paternal smoking; CYP1A1; Interaction; Haplotype
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BULKY DNA-ADDUCTS; PARENTAL SMOKING;
CIGARETTE-SMOKING; MATERNAL SMOKING; ENVIRONMENTAL-FACTORS;
ALCOHOL-CONSUMPTION; TOBACCO-SMOKE; LUNG-CANCER; PREGNANCY
AB We conducted a case-control study to evaluate the association between paternal smoking and childhood leukemia and to evaluate potential modification by polymorphisms in CYP1A1. Histologically confirmed childhood leukemia cases (n = 164) and non-cancer controls (n = 164) were recruited front three teaching, hospitals in Seoul. Korea. Five single nucleotide polymorphisms in CYP1A1 (-17961T>C. -9893G>A. 1462V. 1188C>T (*2A), and 11599C>G) were genotyped and haplotypes were estimated by the expectation-maximization method. We also conducted a meta-analysis of 12 studies that have reported the association between paternal smoking and childhood leukemia risk. Paternal smoking at home was associated with all leukemias (OR = 1.8. 95% CI = 1.1-2.8) and acute lymphoblastic leukemia (ALL) (2.0, 1.2-3.4). Ail increasing trend in risk was observed for pack-years smoked after birth (P(trend) = 0.06 and 0.02, respectively) and the number of smokers in the home during, the child's life (P(trend) =0.05 and 0.03. respectively). Among those without the CGACC haplotype, ALL risk was significantly increased by the father's smoking at home (2.8. 1.5-5.3) and the presence of at least one smoker in the home (2.3, 1.2-4.4). and the test for interaction was significant (P(interaction) = 0.03 and 0.02, respectively). The meta-analysis showed that overall paternal smoking (1.13. 1.04-1.24) and smoking before the pregnancy of the child (1.12, 1.04-1.21) were significantly associated with childhood leukemia risk. Our results suggest that paternal smoking is a risk factor for childhood leukemia and the effect may be modified by CYP1A1 genotype. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Lee, Kyoun -Mu; Han, Sohee; Ahn, Yoon-Ok; Kang, Daehee] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, Seoul, South Korea.
[Lee, Kyoun -Mu; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ahn, Hyo Seop; Kang, Hyoung Jin; Choi, Hyung Soo; Shin, Hee Young] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Pediat, Seoul, South Korea.
[Koo, Hong-Hoe] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul, South Korea.
[Seo, Jong-Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pediat, Seoul, South Korea.
[Choi, Ji-Eun] Borame Hosp, Dept Pediat, Seoul, South Korea.
RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, 28 Yongon Dong, Seoul, South Korea.
EM dhkang@snu.ac.kr
RI Kang, Hyoung Jin/J-2730-2012; Kang, Dae Hee/E-8631-2012; Ahn,
Yoon-Ok/J-5530-2012; Shin, Hee Young/J-2766-2012; Choi, Ji
Eun/J-5696-2012
FU Korea Electrotechnology Research Institute; Ministry of Knowledge
Economy (MKE); Korea Health 21 RD Project; Ministry of Health, Welfare
and Family Affairs, Republic of Korea [A030001: 03-PJ10-PG13-GD01-0002]
FX We gratefully acknowledge the individuals who participated in the
research and the clinicians who gave permission for us to approach their
patients. This research was funded by Korea Electrotechnology Research
Institute, Ministry of Knowledge Economy (MKE) and by a grant of the
Korea Health 21 R&D Project, Ministry of Health, Welfare and Family
Affairs, Republic of Korea (A030001: 03-PJ10-PG13-GD01-0002).
NR 45
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U1 0
U2 11
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 FEB
PY 2009
VL 33
IS 2
BP 250
EP 258
DI 10.1016/j.leukres.2008.06.031
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 396FA
UT WOS:000262576400010
PM 18691756
ER
PT J
AU Doria-Rose, VP
Marcus, PM
AF Doria-Rose, V. Paul
Marcus, Pamela M.
TI Death certificates provide an adequate source of cause of death
information when evaluating lung cancer mortality: An example from the
Mayo Lung Project
SO LUNG CANCER
LA English
DT Article
DE Lung cancer; Death certificate; Mortality; Sensitivity; Specificity
ID PROSTATE-CANCER; MELANOMA
AB To assess the accuracy of death certificates in assigning lung cancer as the underlying cause of death, death certificate data were compared to mortality review committee-determined causes of death among participants in the Mayo Lung Project. Further, the impact of death certificate misclassification on lung cancer mortality rates and Cox proportional hazards models was evaluated. The Mayo Lung Project (1971-1983) was a randomized controlled trial of lung cancer screening; participants were male smokers aged 45 years and older who were seen as outpatients at the Mayo Clinic in Rochester, Minnesota. Overall there were 237 lung cancer deaths according to mortality review, and 224 according to the death certificate (sensitivity 88.6 percent, 95 percent confidence interval (CI) 83.9, 92.4; specificity 99.1 percent, 95 percent CI 98.6, 99.5). As compared to the mortality review committee's determination, the use of death certificate data resulted only in slight decreases to the calculated lung cancer mortality rates for each screening arm, and did not result in appreciable changes to hazard ratios for lung cancer mortality in Cox regression models. In these data, death certificates were sufficiently sensitive and specific such that their use did not result in a meaningful change to mortality-based outcomes. Published by Elsevier Ireland Ltd.
C1 [Doria-Rose, V. Paul] NCI, Dept Hlth & Human Serv, NIH, Canc Prevent Div,Biometry Res Grp, Bethesda, MD 20892 USA.
[Doria-Rose, V. Paul] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
RP Doria-Rose, VP (reprint author), NCI, Dept Hlth & Human Serv, NIH, Canc Prevent Div,Biometry Res Grp, 6130 Execut Blvd,Suite 3131, Bethesda, MD 20892 USA.
EM doriaro@mail.nih.gov
OI Doria-Rose, Vincent/0000-0002-8802-5143
FU National Cancer Institute Research Contract [N01-CN-53886]; Cancer
Prevention Fellowship Program; Office of Preventive Oncology, National
Cancer Institute
FX The Mayo Lung Project was supported by National Cancer Institute
Research Contract N01-CN-53886. This analysis had additional support
from the Cancer Prevention Fellowship Program, Office of Preventive
Oncology, National Cancer Institute. The authors would like to thank
Robert Fontana and Eric Bergstralh for sharing their extensive knowledge
of the Mayo Lung Project data.
NR 23
TC 37
Z9 37
U1 2
U2 5
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 FEB
PY 2009
VL 63
IS 2
BP 295
EP 300
DI 10.1016/j.lungcan.2008.05.019
PG 6
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 402NP
UT WOS:000263020700021
PM 18585822
ER
PT J
AU Kukekova, AV
Goldstein, O
Johnson, JL
Richardson, MA
Pearce-Kelling, SE
Swaroop, A
Friedman, JS
Aguirre, GD
Acland, GM
AF Kukekova, Anna V.
Goldstein, Orly
Johnson, Jennifer L.
Richardson, Malcolm A.
Pearce-Kelling, Susan E.
Swaroop, Anand
Friedman, James S.
Aguirre, Gustavo D.
Acland, Gregory M.
TI Canine RD3 mutation establishes rod-cone dysplasia type 2 (rcd2) as
ortholog of human and murine rd3
SO MAMMALIAN GENOME
LA English
DT Article
ID CYCLIC-NUCLEOTIDE-METABOLISM; EARLY RETINAL DEGENERATION;
RETINITIS-PIGMENTOSA; LINKAGE DISEQUILIBRIUM; INHERITED RETINOPATHY;
DOMESTIC DOG; BREEDS; GENOME; COLLIE; LOCUS
AB Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend the open reading frame. Thus, combined meiotic linkage and LD mapping within a single canine breed can yield critical reduction of the disease interval when appropriate advantage is taken of within-breed population structure. This should permit a similar approach to tackle other hereditary traits that segregate in single closed populations.
C1 [Kukekova, Anna V.; Goldstein, Orly; Johnson, Jennifer L.; Richardson, Malcolm A.; Pearce-Kelling, Susan E.; Acland, Gregory M.] Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
[Richardson, Malcolm A.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03766 USA.
[Swaroop, Anand] Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48105 USA.
[Swaroop, Anand; Friedman, James S.] NEI, NIH, Bethesda, MD 20892 USA.
[Aguirre, Gustavo D.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
RP Acland, GM (reprint author), Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Hungerford Hill Rd, Ithaca, NY 14853 USA.
EM gma2@cornell.edu
OI Johnson, Jennifer/0000-0002-3339-4419; Swaroop,
Anand/0000-0002-1975-1141
FU Foundation Fighting Blindness, [EY006855, MH077811]; Morris Animal
Foundation,; Collie Health Foundation; Cornell VERGE Initiative
FX We are grateful to Amanda Nickle, Gerri Antonini, and the staff of the
RDS facility for research support. This study was supported by EY006855,
MH077811, Foundation Fighting Blindness, Morris Animal Foundation,
Collie Health Foundation, and Cornell VERGE Initiative. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the supporting institutions or
foundations.
NR 34
TC 27
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U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
EI 1432-1777
J9 MAMM GENOME
JI Mamm. Genome
PD FEB
PY 2009
VL 20
IS 2
BP 109
EP 123
DI 10.1007/s00335-008-9163-4
PG 15
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 404JN
UT WOS:000263147900005
PM 19130129
ER
PT J
AU Sumner, AE
Luercio, MF
Frempong, BA
Ricks, M
Sen, S
Kushner, H
Tulloch-Reid, MK
AF Sumner, Anne E.
Luercio, Marcella F.
Frempong, Barbara A.
Ricks, Madia
Sen, Sabyasachi
Kushner, Harvey
Tulloch-Reid, Marshall K.
TI Validity of the reduced-sample insulin modified frequently-sampled
intravenous glucose tolerance test using the nonlinear regression
approach
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID MINIMAL-MODEL; ASSESSING AGREEMENT; SENSITIVITY; POPULATION; RESISTANCE;
PROTOCOLS
AB The disposition index, the product of the insulin sensitivity index (S(l)) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with S(l) calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate S(l) using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With S(l) from the Full-Sample-IM-FSIGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between S(l) from the Full- and Reduced-Sample-IM-FSIGT protocols. One hundred African Americans (body mass index, 31.3 +/- 7.6 kg/m(2) [mean +/- SD]; range, 19.0-56.9 kg/m(2)) had FSIGTs. Glucose (0.3 g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For the Full-Sample-IM-FSIGT, S(l) was calculated based on the glucose and insulin samples taken at -1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70 80, 90 100 120, 150, and 180 minutes. For the Reduced-Sample-FSIGT, S(l) was calculated based on the time points that appear in bold. Agreement was determined by Spearman correlation, concordance, and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles S(l). Insulin resistance was defined by the lowest tertile of S, from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and kappa statistic. We found that the rate of failure of resolution of S(l) by the Reduced-Sample-IM-FSIGT was 3% (3/100). For the remaining 97 subjects, S(l) for the Full- and Reduced-Sample-IM-FSIGTs were as follows: 3.76 +/- 2.41 L mU(-1) min(-1) (range, 0.58-14.50) and 4.29 +/- 2.89 L mU(-1) min(-1) (range, 0.52-14.42); relative error, 21% +/- 18%; Spearman r = 0.97; and concordance, 0.94 (both P < .001). After log transformation, the Bland-Altman limits of agreement were -0.29 and 0.53. The exact agreement for distribution of the population in the insulin-resistant tertile vs the insulin-sensitive tertiles was 92%, kappa of 0.82 +/- 0.06. Using the nonlinear regression approach and data from the Reduced-Sample-IM-FSIGT in subjects with a wide range of insulin sensitivity, failure to resolve S(l) occurred in only 3% of subjects. The agreement and maintenance of rank order of S(l) between protocols support the use of the nonlinear regression approach to the minimal model and the Reduced-Sainple-IM-FSIGT in clinical studies. Published by Elsevier Inc.
C1 [Sumner, Anne E.; Luercio, Marcella F.; Frempong, Barbara A.; Ricks, Madia; Sen, Sabyasachi] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Kushner, Harvey] BioMed Comp Inst, Philadelphia, PA 19115 USA.
[Tulloch-Reid, Marshall K.] Univ W Indies, Res Inst Trop Med, Epidemiol Res Unit, Kingston 7, Jamaica.
RP Sumner, AE (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM annes@intra.niddk.nih.gov
RI Tulloch-Reid, Marshall/E-4383-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the intramural research program at the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 19
TC 7
Z9 7
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD FEB
PY 2009
VL 58
IS 2
BP 220
EP 225
DI 10.1016/j.metabol.2008.09.017
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 402WS
UT WOS:000263044400011
PM 19154955
ER
PT J
AU Robitaille, L
Mamer, OA
Miller, WH
Levine, M
Assouline, S
Melnychuk, D
Rousseau, C
Hoffer, LJ
AF Robitaille, Line
Mamer, Orval A.
Miller, Wilson H., Jr.
Levine, Mark
Assouline, Sarit
Melnychuk, David
Rousseau, Caroline
Hoffer, L. John
TI Oxalic acid excretion after intravenous ascorbic acid administration
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID TOTAL PARENTERAL-NUTRITION; ACUTE OXALATE NEPHROPATHY; VITAMIN-C INTAKE;
HEMODIALYSIS-PATIENTS; URINARY OXALATE; LONG-TERM; STABILITY;
OXALOGENESIS; SECONDARY; ANEMIA
AB Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when Studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Robitaille, Line; Miller, Wilson H., Jr.; Hoffer, L. John] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Mamer, Orval A.; Hoffer, L. John] McGill Univ, Mass Spectrometry Lab, Montreal, PQ H3A 1A4, Canada.
[Levine, Mark] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Assouline, Sarit; Melnychuk, David; Rousseau, Caroline] McGill Univ, Jewish Gen Hosp, Montreal Ctr Expt Therapeut Canc, Montreal, PQ H3T 1E2, Canada.
RP Hoffer, LJ (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
EM l.hoffer@mcgill.ca
FU Lotte and John Hecht Memorial Foundation; Canadian Institutes of Health
Research [PRG-80160]; Intramural Research Program; National Institutes
of Health/National Institute of Diabetes and Digestive and Kidney
Diseases
FX This study was funded by a grant from the Lotte and John Hecht Memorial
Foundation and from Research Resource Program Grant PRG-80160 from the
Canadian Institutes of Health Research. WHM is a Chercheur National of
the Fonds de la Recherche en Sante du Quebec. ML is supported by the
Intramural Research Program, National Institutes of Health/National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 38
TC 15
Z9 15
U1 2
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD FEB
PY 2009
VL 58
IS 2
BP 263
EP 269
DI 10.1016/j.metabol.2008.09.023
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 402WS
UT WOS:000263044400017
PM 19154961
ER
PT J
AU Polgar, O
Deeken, JF
Ediriwickrema, LS
Tamaki, A
Steinberg, SM
Robey, RW
Bates, SE
AF Polgar, Orsolya
Deeken, John F.
Ediriwickrema, Lilangi S.
Tamaki, Akina
Steinberg, Seth M.
Robey, Robert W.
Bates, Susan E.
TI The 315-316 deletion determines the BXP-21 antibody epitope but has no
effect on the function of wild type ABCG2 or the Q141K variant
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE ABCG2; ABC transporter; Multidrug resistance; Single nucleotide
polymorphism; Mitoxantrone; Pheophorbide a
ID SINGLE NUCLEOTIDE POLYMORPHISMS; TYROSINE KINASE INHIBITORS; RESISTANCE
PROTEIN ABCG2; BREAST-CANCER CELLS; MULTIDRUG TRANSPORTER;
SUBSTRATE-SPECIFICITY; ACQUIRED MUTATIONS; HALF-TRANSPORTER; ATP
HYDROLYSIS; BINDING
AB ABCG2 is a half-transporter initially described in multidrug-resistant cancer cells and lately identified as an important factor in the pharmacokinetics of its substrates. Q141K is by far the most intensively studied single nucleotide polymorphism of ABCG2 with potential clinical relevance. Here we used stably transfected HEK cells to study the Q141K polymorphism together with the deletion of amino acids 315-316, which were recently reported to coexist in two cancer cell lines (A549 and SK-OV-3). Functional studies confirmed our previous report that when normalized to surface expression, Q141K has impaired transport of mitoxantrone. This result was extended to include the ABCG2-specific substrate pheophorbide a. While we found no functional consequence of deleting amino acids 315 and 316, we did find that the deletion mutant is no longer recognized by the BXP-21 antibody. We conclude that amino acids 315 and 316 form part of the epitope for the BXP-21 antibody.
C1 [Polgar, Orsolya; Ediriwickrema, Lilangi S.; Tamaki, Akina; Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Deeken, John F.] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
FU NIH; National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 34
TC 3
Z9 3
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD FEB
PY 2009
VL 322
IS 1-2
BP 63
EP 71
DI 10.1007/s11010-008-9940-0
PG 9
WC Cell Biology
SC Cell Biology
GA 403XT
UT WOS:000263116000007
PM 19002564
ER
PT J
AU Matsuda, H
Paul, BD
Choi, CY
Hasebe, T
Shi, YB
AF Matsuda, Hiroki
Paul, Bindu D.
Choi, Cheol Young
Hasebe, Takashi
Shi, Yun-Bo
TI Novel Functions of Protein Arginine Methyltransferase 1 in Thyroid
Hormone Receptor-Mediated Transcription and in the Regulation of
Metamorphic Rate in Xenopus laevis
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID IN-VIVO ANALYSIS; AMPHIBIAN METAMORPHOSIS; GENE-EXPRESSION;
POSTEMBRYONIC DEVELOPMENT; CELL-PROLIFERATION; HISTONE H4; EPITHELIAL
APOPTOSIS; COREPRESSOR COMPLEX; FROG METAMORPHOSIS; NEURAL FATE
AB Protein arginine methyltransferase 1 (PRMT1) acts as a transcription coactivator for nuclear receptors through histone H4 R3 methylation. The in vivo function of PRMT1 is largely unknown. Here we investigated the role of PRMT1 in thyroid hormone (T3) receptor (TR)-mediated transcription in vivo during vertebrate development. By using intestinal remodeling during T3-dependent Xenopus laevis metamorphosis for in vivo molecular analysis, we first showed that PRMT1 expression was upregulated during metamorphosis when both TR and T3 were present. We then demonstrated a role for PRMT1 in TR-mediated transcription by showing that PRMT1 enhanced transcriptional activation by liganded TR in the frog oocyte transcription system and was recruited to the T3 response element (TRE) of the target promoter in the oocyte, as well as to endogenous TREs during frog metamorphosis. Surprisingly, we found that PRMT1 was only transiently recruited to the TREs in the target during metamorphosis and observed no PRMT1 recruitment to TREs at the climax of intestinal remodeling when both PRMT1 and T3 were at peak levels. Mechanistically, we showed that overexpression of PRMT1 enhanced TR binding to TREs both in the frog oocyte model system and during metamorphosis. More importantly, transgenic overexpression of PRMT1 enhanced gene activation in vivo and accelerated both natural and T3-induced metamorphosis. These results thus indicate that PRMT1 functions transiently as a coactivator in TR-mediated transcription by enhancing TR-TRE binding and further suggest that PRMT1 has tissue-specific roles in regulating the rate of metamorphosis.
C1 [Shi, Yun-Bo] NICHHD, LGRD, NIH, PCRM,Sect Mol Morphogenesis, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHHD, LGRD, NIH, PCRM,Sect Mol Morphogenesis, Bldg 18T,Rm 106, Bethesda, MD 20892 USA.
EM Shi@helix.nih.gov
FU Intramural Research Program of NICHD; NIH
FX This research was supported by the Intramural Research Program of NICHD,
NIH.
NR 89
TC 26
Z9 27
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 FEB 1
PY 2009
VL 29
IS 3
BP 745
EP 757
DI 10.1128/MCB.00827-08
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 396RP
UT WOS:000262609100012
PM 19047371
ER
PT J
AU Han, Q
Robinson, H
Cai, T
Tagle, DA
Li, JY
AF Han, Qian
Robinson, Howard
Cai, Tao
Tagle, Danilo A.
Li, Jianyong
TI Biochemical and Structural Properties of Mouse Kynurenine
Aminotransferase III
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SPONTANEOUSLY HYPERTENSIVE-RATS; GLUTAMINE TRANSAMINASE-K; EXCITATORY
AMINO-ACIDS; CRYSTAL-STRUCTURE; SUBSTRATE-SPECIFICITY; HUMAN BRAIN;
ASPARTATE-AMINOTRANSFERASE; SYNAPTIC-TRANSMISSION; HUNTINGTONS-DISEASE;
NICOTINIC RECEPTORS
AB Kynurenine aminotransferase III (KAT III) has been considered to be involved in the production of mammalian brain kynurenic acid (KYNA), which plays an important role in protecting neurons from over-stimulation by excitatory neurotransmitters. The enzyme was identified based on its high sequence identity with mammalian KAT I, but its activity toward kynurenine and its structural characteristics have not been established. In this study, the biochemical and structural properties of mouse KAT III (mKAT III) were determined. Specifically, mKAT III cDNA was amplified from a mouse brain cDNA library, and its recombinant protein was expressed in an insect cell protein expression system. We established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60 C. In addition, mKAT III is active toward a number of other amino acids. Its activity toward kynurenine is significantly decreased in the presence of methionine, histidine, glutamine, leucine, cysteine, and 3-hydroxykynurenine. Through macromolecular crystallography, we determined the mKAT III crystal structure and its structures in complex with kynurenine and glutamine. Structural analysis revealed the overall architecture of mKAT III and its cofactor binding site and active center residues. This is the first report concerning the biochemical characteristics and crystal structures of KAT III enzymes and provides a basis toward understanding the overall physiological role of mammalian KAT III in vivo and insight into regulating the levels of endogenous KYNA through modulation of the enzyme in the mouse brain.
C1 [Han, Qian; Li, Jianyong] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA.
[Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
[Cai, Tao] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA.
[Tagle, Danilo A.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Li, JY (reprint author), Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA.
EM lij@vt.edu
RI Han, Qian/J-8696-2014
OI Han, Qian/0000-0001-6245-5252
FU NIH; Agriculture and Life Sciences, Virginia Tech
FX We acknowledge the support of the Virginia Tech Department of Biological
Sciences in the use of their X-ray facility and are grateful to Nancy
Vogelaar, Chris Ceccarelli (Oxford Diffraction), and Florian Schubot for
engaging us in helpful discussions.
NR 60
TC 36
Z9 38
U1 2
U2 9
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 FEB 1
PY 2009
VL 29
IS 3
BP 784
EP 793
DI 10.1128/MCB.01272-08
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 396RP
UT WOS:000262609100015
PM 19029248
ER
PT J
AU Shin, BS
Kim, JR
Acker, MG
Maher, KN
Lorsch, JR
Dever, TE
AF Shin, Byung-Sik
Kim, Joo-Ran
Acker, Michael G.
Maher, Kathryn N.
Lorsch, Jon R.
Dever, Thomas E.
TI rRNA Suppressor of a Eukaryotic Translation Initiation Factor
5B/Initiation Factor 2 Mutant Reveals a Binding Site for Translational
GTPases on the Small Ribosomal Subunit
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ELONGATION-FACTOR TU; AMINOACYL-TRANSFER-RNA; CONFORMATIONAL-CHANGES;
PROTEIN-SYNTHESIS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE;
CRYSTAL-STRUCTURE; 80S RIBOSOME; FACTOR EIF5B; IN-VIVO
AB The translational GTPases promote initiation, elongation, and termination of protein synthesis by interacting with the ribosome. Mutations that impair GTP hydrolysis by eukaryotic translation initiation factor 5B/initiation factor 2 (eIF5B/IF2) impair yeast cell growth due to failure to dissociate from the ribosome following subunit joining. A mutation in helix h5 of the 18S rRNA in the 40S ribosomal subunit and intragenic mutations in domain II of eIF5B suppress the toxic effects associated with expression of the eIF5B-H480I GTPase-deficient mutant in yeast by lowering the ribosome binding affinity of eIF5B. Hydroxyl radical mapping experiments reveal that the domain II suppressors interface with the body of the 40S subunit in the vicinity of helix h5. As the helix h5 mutation also impairs elongation factor function, the rRNA and eIF5B suppressor mutations provide in vivo evidence supporting a functionally important docking of domain II of the translational GTPases on the body of the small ribosomal subunit.
C1 [Shin, Byung-Sik; Kim, Joo-Ran; Maher, Kathryn N.; Dever, Thomas E.] NICHHD, Lab Gene Regulat & Dev Hlth, NIH, Bethesda, MD 20892 USA.
[Acker, Michael G.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev Hlth, NIH, Bldg 6A,Rm B1A-03,6 Ctr Dr, Bethesda, MD 20892 USA.
EM tdever@nih.gov
OI Dever, Thomas/0000-0001-7120-9678
FU National Institute of Child Health and Development; National Institutes
of Health; American Cancer Society [RSG-03-156-01-GMC]
FX This work was supported in part by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and
Development, National Institutes of Health (T.E.D.), and by American
Cancer Society grant RSG-03-156-01-GMC (J.R.L.).
NR 57
TC 13
Z9 14
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 FEB 1
PY 2009
VL 29
IS 3
BP 808
EP 821
DI 10.1128/MCB.00896-08
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 396RP
UT WOS:000262609100017
PM 19029250
ER
PT J
AU Chae, JI
Ju, SK
Lee, MK
Park, JH
Yoon, JH
Shim, JH
Lee, DS
AF Chae, J. I.
Ju, S. K.
Lee, M. K.
Park, J. H.
Yoon, J. H.
Shim, J. H.
Lee, D. S.
TI cDNA cloning and analysis of tissue-specific gene expression of rat
urocortin II
SO MOLECULAR BIOLOGY
LA English
DT Article
DE urocortin II; recombinant proteins; FACS
ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR CRF; BINDING-PROTEIN;
NEUROPEPTIDE; RECEPTORS; PEPTIDE; HORMONE; FAMILY; GLUCOCORTICOIDS;
SECRETION
AB The corticotropin-releasing hormone (CRH) family of neuropeptides includes CRH (a 41-amino acid hypothalamic peptide) and urocortin. Corticotropin-releasing factor (CRF), a peptide first isolated from mammalian, plays an important role in the regulation of the pituitary-adrenal axis, and in endocrine, autonomic, immune and behavioral responses to stress. In this study, we cloned rat urocortin II (UCN II) cDNA from rat mid-brain by RT-PCR. The rat UCN II clone contained an open reading frame (ORF) 109 amino acids which shared 90% and 63% homology with mouse and human homologues, respectively. The expression of UCN II mRNA is mainly distributed in bone marrow, ovary, uterus, hypophysis, adrenal gland, and skin. In this study, rat recombinant UCN was expressed in E. coli and purified in active form. Furthermore, purified recombinant UCN II protein specifically binds to CRF receptor 2 in rat ROS 17 / 2.8 and GH3 cells by flow-cytometry analysis. UCN II cDNA clone obtained in this study will be useful for further investigation on behavioral responses to stress in rats.
C1 [Chae, J. I.; Yoon, J. H.] Korea Res Inst Biosci & Biotechnol, Ctr Regenerat Med, Taejon 305333, South Korea.
[Ju, S. K.; Lee, M. K.] Korea Res Inst Biosci & Biotechnol, Om & Integrat Res Ctr, Taejon 305333, South Korea.
[Park, J. H.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Shim, J. H.] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Lee, D. S.] Kyungpook Natl Univ, Coll Nat Sci, Taegu 702701, South Korea.
RP Chae, JI (reprint author), Korea Res Inst Biosci & Biotechnol, Ctr Regenerat Med, Taejon 305333, South Korea.
EM lee1@knu.ac.kr
FU Kyungpook National University Research Fund, Republic of Korea
FX This research was supported by Kyungpook National University Research
Fund, 2007, Republic of Korea.
NR 23
TC 1
Z9 1
U1 0
U2 0
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0026-8933
J9 MOL BIOL+
JI Mol. Biol.
PD FEB
PY 2009
VL 43
IS 1
BP 82
EP 87
DI 10.1134/S0026893309010117
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 411WS
UT WOS:000263684800011
ER
PT J
AU Hur, JH
Van Doninck, K
Mandigo, ML
Meselson, M
AF Hur, Jae H.
Van Doninck, Karine
Mandigo, Morgan L.
Meselson, Matthew
TI Degenerate Tetraploidy Was Established Before Bdelloid Rotifer Families
Diverged
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
ID PHYLUM ROTIFERA; CLUSTAL-W; ALIGNMENT; RATES; GENE; DNA; SUBSTITUTION;
EVOLUTION; DATABASE
AB Rotifers of Class Bdelloidea are abundant freshwater invertebrates known for their remarkable ability to survive desiccation and their lack of males and meiosis. Sequencing and annotation of approximately 50-kb regions containing the four hsp82 heat shock genes of the bdelloid Philodina roseola, each located on a separate chromosome, have suggested that its genome is that of a degenerate tetraploid. In order to determine whether a similar structure exists in a bdelloid distantly related to P. roseola and if degenerate tetraploidy was established before the two species separated, we sequenced regions containing the hsp82 genes of a bdelloid belonging to a different family, Adineta vaga, and the histone gene clusters of P. roseola and A. vaga. Our findings are entirely consistent with degenerate tetraploidy and show that it was established before the two bdelloid families diverged and therefore probably before the bdelloid radiation.
C1 [Hur, Jae H.; Van Doninck, Karine; Mandigo, Morgan L.; Meselson, Matthew] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Mandigo, Morgan L.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Van Doninck, Karine] Univ Namur FUNDP, Dept Biol, URBO, Namur, Belgium.
RP Hur, JH (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM msm@wjh.harvard.edu
FU US National Science Foundation; Belgian - American Educational
Foundation; Fulbright Program
FX We thank David and Jessica Mark Welch for helpful discussions and
technical assistance at every stage of the experiments. Other members of
the Josephine Bay Paul Center for Comparative Molecular Biology and
Evolution at the Marine Biological Laboratory, Woods Hole, MA provided
assistance in fosmid sequencing and contig construction. At Harvard,
Beth Weiner and others in the Kleckner laboratory provided access to
their fluorescent microscope and instruction in its use, Christian Daly,
George Kenty, and Peter Wang provided assistance in library
construction, and members of the Maniatis laboratory and Kevin McMullen
provided assistance in library screening. Financial support was provided
by the US National Science Foundation (M. M.), the Belgian - American
Educational Foundation (K. V. D.), and the Fulbright Program (K. V. D.).
NR 38
TC 22
Z9 23
U1 3
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD FEB
PY 2009
VL 26
IS 2
BP 375
EP 383
DI 10.1093/molbev/msn260
PG 9
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 395LN
UT WOS:000262525700013
PM 18996928
ER
PT J
AU Bryja, V
Andersson, ER
Schambony, A
Esner, M
Bryjova, L
Biris, KK
Hall, AC
Kraft, B
Cajanek, L
Yamaguchi, TP
Buckingham, M
Arenas, E
AF Bryja, Vitezslav
Andersson, Emma R.
Schambony, Alexandra
Esner, Milan
Bryjova, Lenka
Biris, Kristin K.
Hall, Anita C.
Kraft, Bianca
Cajanek, Lukas
Yamaguchi, Terry P.
Buckingham, Margaret
Arenas, Ernest
TI The Extracellular Domain of Lrp5/6 Inhibits Noncanonical Wnt Signaling
In Vivo
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID CONVERGENT EXTENSION MOVEMENTS; OUTFLOW TRACT DEVELOPMENT; PLANAR CELL
POLARITY; WNT/BETA-CATENIN; BETA-CATENIN; DISHEVELLED PHOSPHORYLATION;
GASTRULATION MOVEMENTS; XENOPUS GASTRULATION; DOPAMINERGIC CELLS;
RECEPTOR
AB Lrp5/6 are crucial coreceptors for Wnt/beta-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with Wnt5a, but that this does not lead to phosphorylation of Lrp6 or activation of the Wnt/beta-catenin pathway. Overexpression of Lrp6 blocks activation of the Wnt5a downstream target Rac1, and this effect is dependent on intact Lrp6 extracellular domains. These results suggested that the extracellular domain of Lrp6 inhibits noncanonical Wnt signaling in vitro. In vivo, Lrp6-/- mice exhibited exencephaly and a heart phenotype. Surprisingly, these defects were rescued by deletion of Wnt5a, indicating that the phenotypes resulted from noncanonical Wnt gain-of-function. Similarly, Lrp5 and Lrp6 antisense morpholino-treated Xenopus embryos exhibited convergent extension and heart phenotypes that were rescued by knockdown of noncanonical XWnt5a and XWnt11. Thus, we provide evidence that the extracellular domains of Lrp5/6 behave as physiologically relevant inhibitors of noncanonical Wnt signaling during Xenopus and mouse development in vivo.
C1 [Bryja, Vitezslav; Andersson, Emma R.; Bryjova, Lenka; Hall, Anita C.; Cajanek, Lukas; Arenas, Ernest] Karolinska Inst, Ctr Dev Biol & Regenerat Med, Mol Neurobiol Lab, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
[Schambony, Alexandra; Kraft, Bianca] Univ Karlsruhe TH, Inst Zool 2, D-76131 Karlsruhe, Germany.
[Esner, Milan; Buckingham, Margaret] Inst Pasteur, CNRS, Unite Rech Associee 2578, Dept Dev Biol, F-75724 Paris, France.
[Biris, Kristin K.; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Bryja, Vitezslav; Bryjova, Lenka] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, Brno 60177, Czech Republic.
[Bryja, Vitezslav; Bryjova, Lenka] Masaryk Univ, Fac Sci, Inst Expt Biol, Brno 60200, Czech Republic.
RP Bryja, V (reprint author), Karolinska Inst, Ctr Dev Biol & Regenerat Med, Mol Neurobiol Lab, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
EM bryja@sci.muni.cz; ernest.arenas@ki.se
RI Bryja, Vit?zslav/H-1925-2014; Andersson, Emma/J-4236-2012;
OI Bryja, Vit?zslav/0000-0002-9136-5085; Andersson,
Emma/0000-0002-8608-625X; Cajanek, Lukas/0000-0003-2914-8589; Schambony,
Alexandra/0000-0001-8771-5487; Arenas, Ernest/0000-0003-0197-6577
NR 57
TC 53
Z9 54
U1 0
U2 7
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD FEB
PY 2009
VL 20
IS 3
BP 924
EP 936
DI 10.1091/mbc.E08-07-0711
PG 13
WC Cell Biology
SC Cell Biology
GA 402RX
UT WOS:000263031900017
PM 19056682
ER
PT J
AU Madhavan, S
Zenklusen, JC
Kotliarov, Y
Sahni, H
Fine, HA
Buetow, K
AF Madhavan, Subha
Zenklusen, Jean-Claude
Kotliarov, Yuri
Sahni, Himanso
Fine, Howard A.
Buetow, Kenneth
TI Rembrandt: Helping Personalized Medicine Become a Reality through
Integrative Translational Research
SO MOLECULAR CANCER RESEARCH
LA English
DT Editorial Material
ID MOLECULAR SUBTYPES; GLIOBLASTOMA; CLASSIFICATION; TUMORS; BRAIN; CELLS
AB Finding better therapies for the treatment of brain tumors Is hampered by the lack of consistently obtained molecular data In a large sample set and the ability to Integrate biomedical data from disparate sources enabling translation of therapies from bench to bedside. Hence, a critical factor in the advancement of biomedical research and clinical translation is the ease with which data can be Integrated, redistributed, and analyzed both within and across functional domains. Novel biomedical informatics infrastructure and tools are essential for developing Individualized patient treatment based on the specific genomic signatures In each patient's tumor. Here, we present Repository of Molecular Brain Neoplasia Data (Rembrandt), a cancer clinical genomics database and a Web-based data mining and analysis platform aimed at facilitating discovery by connecting the dots between clinical Information and genomic characterization data. To date, Rembrandt contains data generated through the Glioma Molecular Diagnostic Initiative from 874 glioma specimens comprising similar to 566 gene expression arrays, 834 copy number arrays, and 13,472 clinical phenotype data points. Data can be queried and visualized for a selected gene across all data platforms or for multiple genes In a selected platform. Additionally, gene sets can be limited to clinically Important annotations including secreted, kinase, membrane, and known gene-anomaly pairs to facilitate the discovery of novel biomarkers and therapeutic targets. We believe that Rembrandt represents a prototype of how high-throughput genomic and clinical data can be integrated in a way that will allow expeditious and efficient translation of laboratory discoveries to the clinic. (Mol Cancer Res 2009;7(2):157-67)
C1 [Zenklusen, Jean-Claude; Kotliarov, Yuri; Fine, Howard A.] NCI, Ctr Canc Res, Neurooncol Branch, Bethesda, MD 20892 USA.
[Madhavan, Subha; Buetow, Kenneth] NCI, Ctr Biomed Informat & Informat Technol, Neurooncol Branch, Bethesda, MD 20892 USA.
[Sahni, Himanso] Sci Applicat Int Corp, San Diego, CA 92121 USA.
RP Zenklusen, JC (reprint author), NCI, Ctr Canc Res, Neurooncol Branch, 37 Convent Dr,Room 1142B,MSC 4254, Bethesda, MD 20892 USA.
EM jz44m@nih.gov
RI Kotliarov, Yuri/B-6938-2017
FU Intramural NIH HHS [Z99 CA999999]
NR 17
TC 151
Z9 156
U1 3
U2 13
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 FEB
PY 2009
VL 7
IS 2
BP 157
EP 167
DI 10.1158/1541-7786.MCR-08-0435
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 410MG
UT WOS:000263580800001
PM 19208739
ER
PT J
AU Palmer, MB
Majumder, P
Cooper, JC
Yoon, H
Wade, PA
Boss, JM
AF Palmer, Matthew B.
Majumder, Parimal
Cooper, John C.
Yoon, Hyesuk
Wade, Paul A.
Boss, Jeremy M.
TI Yin Yang 1 Regulates the Expression of Snail through a Distal Enhancer
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITIONS; E-CADHERIN EXPRESSION; TRANSCRIPTION
FACTOR; MELANOMA-CELLS; UP-REGULATION; DEPENDENT TRANSCRIPTION;
ESTROGEN-RECEPTOR; BREAST-CARCINOMA; YY1; GENE
AB Expression of the Snail gene is required for the epithelial-mesenchymal transitions that accompany mammalian gastrulation, neural crest migration, and organ formation. Pathologic expression of Snail contributes to the migratory capacity of invasive tumors, Including melanomas. To investigate the mechanism of Snail up-regulation In human melanoma cells, a conserved enhancer located 3' of the Snail gene was analyzed. An overlapping Ets and yin yang 1 (YY1) consensus sequence, In addition to a SOX consensus sequence, was required for full enhancer activity. Proteins specifically binding these sequences were detected by electrophoretic mobility shift assay. The Ets/YY1 binding activity was purified by DNA-affinity chromatography and identified as YY1. Although ubiquitously expressed, YY1 was bound at the Snail 3' enhancer in vivo In Snail-expressing cells but not In cells that did not express Snail. Knockdown of YY1 in A375 cells led to decreased Snail expression. These results identify a role for YY1 in regulating transcription of Snail In melanoma cells through binding to the Snag 3' enhancer. (Mol Cancer Res 2009;7(2):221-9)
C1 [Palmer, Matthew B.; Majumder, Parimal; Cooper, John C.; Yoon, Hyesuk; Boss, Jeremy M.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Wade, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA.
RP Boss, JM (reprint author), Emory Univ, Sch Med, Dept Microbiol & Immunol, 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM boss@microbio.emory.edu
FU National Institute of Environmental Health Sciences; NIH [Z01ES101965];
NIDDK [DK065961]
FX Grant support: Intramural Research Program of the National Institute of
Environmental Health Sciences, NIH grant Z01ES101965 (RA. Wade) and
NIDDK grant DK065961 (J.M. Bass).
NR 48
TC 16
Z9 20
U1 0
U2 0
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 FEB
PY 2009
VL 7
IS 2
BP 221
EP 229
DI 10.1158/1541-7786.MCR-08-0229
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 410MG
UT WOS:000263580800007
PM 19208738
ER
PT J
AU Kyrkanides, S
Yang, MX
Tallents, R
Miller, JN
Brouxhon, S
Harvey, B
AF Kyrkanides, Stephanos
Yang, Meixiang
Tallents, Ross
Miller, Jen-nie
Brouxhon, Sabine
Harvey, Brandon
TI The trigeminal retrograde transfer pathway in LSD gene therapy
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Yang, Meixiang; Tallents, Ross; Miller, Jen-nie; Harvey, Brandon] Univ Rochester, Buffalo, NY USA.
[Harvey, Brandon] Natl Inst Drug Abuse, NIH, Bethesda, MD USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 79
BP S29
EP S29
DI 10.1016/j.ymgme.2008.11.080
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800087
ER
PT J
AU Medin, J
Walia, J
Neschadim, A
Fan, X
Madden, M
Cheung, F
Jaffray, D
Levade, T
Brady, R
McCart, JA
AF Medin, Jeffrey
Walia, Jagdeep
Neschadim, Anton
Fan, Xin
Madden, Melissa
Cheung, Fred
Jaffray, David
Levade, Thierry
Brady, Roscoe
McCart, J. Andrea
TI Outcomes of testing Lentivector-mediated Gene Therapy for Farber Disease
in Non-Human Primates
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Medin, Jeffrey; Walia, Jagdeep; Fan, Xin; Jaffray, David] Ontario Canc Inst, Div Stem Cell & Dev Biol, Univ Hlth Network, Toronto, ON M4X 1K9, Canada.
[Neschadim, Anton] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
[Madden, Melissa] UHN, Anim Resources Ctr, Toronto, ON, Canada.
[Cheung, Fred; Jaffray, David] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada.
[Jaffray, David; McCart, J. Andrea] Toronto Gen Res Inst, Toronto, ON, Canada.
[Levade, Thierry] Univ Toulouse 3, INSERM, Inst Med Mol Rangueil, F-31062 Toulouse, France.
[Brady, Roscoe] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
RI Levade, Thierry/O-8948-2014
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 87
BP S31
EP S31
DI 10.1016/j.ymgme.2008.11.088
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800095
ER
PT J
AU Namboodiri, A
Madhavarao, C
Arun, P
Mog, S
Grunberg, N
Gahl, W
Anikster, Y
Moffett, J
AF Namboodiri, Aryan
Madhavarao, C.
Arun, P.
Mog, S.
Grunberg, N.
Gahl, W.
Anikster, Y.
Moffett, J.
TI Canavan disease treatment using glyceryltriacetate
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Namboodiri, Aryan; Madhavarao, C.; Arun, P.; Mog, S.; Grunberg, N.; Moffett, J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Gahl, W.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 96
BP S33
EP S33
DI 10.1016/j.ymgme.2008.11.097
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800104
ER
PT J
AU Patterson, M
Porter, F
Vaurio, R
Brown, T
AF Patterson, Marc
Porter, Forbes
Vaurio, Rebecca
Brown, Tanya
TI Longitudinal study of cognition in subjects with Niemann-Pick disease,
type C
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 5th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 18-20, 2009
CL San Diego, NV
SP Lysosomal Dis Network
C1 [Patterson, Marc; Brown, Tanya] Mayo Clin, Rochester, MN 55905 USA.
[Porter, Forbes] Natl Inst Hlth, Bethesda, MD USA.
[Vaurio, Rebecca] Kennedy Krieger Inc, Hugo W Moser Res Inst, Kennett Sq, PA USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 101
BP S34
EP S34
DI 10.1016/j.ymgme.2008.11.102
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800109
ER
PT J
AU Puertollano, R
Vergarajauregui, S
Martina, J
AF Puertollano, Rosa
Vergarajauregui, Silvia
Martina, Jose
TI Autophagic dysfunction in mucolipidosis type IV patients
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Puertollano, Rosa; Vergarajauregui, Silvia; Martina, Jose] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 111
BP S36
EP S36
DI 10.1016/j.ymgme.2008.11.112
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800119
ER
PT J
AU Schiffmann, R
Caruso, R
Goldin, E
AF Schiffmann, Raphael
Caruso, Rafael
Goldin, Ehud
TI Mucolipidosis type IV is both a developmental brain disease and a
degenerative retinopathy
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Schiffmann, Raphael] Inst Metab Dis, Dallas, TX USA.
[Caruso, Rafael] NEI, Bethesda, MD 20892 USA.
[Goldin, Ehud] NHGRI, Bethesda, MD 20892 USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 122
BP S39
EP S39
DI 10.1016/j.ymgme.2008.11.123
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800130
ER
PT J
AU Sidranskyu, E
Goker-Alpan, O
AF Sidranskyu, Ellen
Goker-Alpan, Ozlem
TI Gaucher disease and parkinsonism
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Sidranskyu, Ellen; Goker-Alpan, Ozlem] NHGRI, MGB, Bethesda, MD 20892 USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 131
BP S41
EP S41
DI 10.1016/j.ymgme.2008.11.132
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800139
ER
PT J
AU Slaugenhaupt, S
Curcio-Morelli, C
Charles, F
Venugopal, B
Cao, Y
Browning, M
Walkley, S
Pickel, J
Cotman, S
Purpura, DP
AF Slaugenhaupt, Susan
Curcio-Morelli, Cyntia
Charles, Florie
Venugopal, Bhuvarahamurthy
Cao, Yi
Browning, Marsha
Walkley, Steven
Pickel, James
Cotman, Susan
Purpura, Dominck P.
TI Characterization of neuronal storage in the mucolipidosis type IV murine
model
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Slaugenhaupt, Susan; Curcio-Morelli, Cyntia; Charles, Florie; Venugopal, Bhuvarahamurthy; Cao, Yi; Browning, Marsha; Cotman, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Slaugenhaupt, Susan; Curcio-Morelli, Cyntia; Charles, Florie; Venugopal, Bhuvarahamurthy; Cao, Yi; Browning, Marsha; Cotman, Susan] Harvard Univ, Sch Med, Boston, MA USA.
[Walkley, Steven; Purpura, Dominck P.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Dept Neurosci, Bronx, NY 10467 USA.
[Pickel, James] Natl Inst Hlth, NIMH Transgen Core, Bethesda, MD USA.
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 134
BP S41
EP S42
DI 10.1016/j.ymgme.2008.11.135
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800142
ER
PT J
AU Zheng, W
Motabar, O
Liu, K
Goldin, E
Southall, N
Marugan, J
Austin, C
Sidransky, E
AF Zheng, Wei
Motabar, Omid
Liu, Ke
Goldin, Ehud
Southall, Noel
Marugan, Juan
Austin, Christopher
Sidransky, Ellen
TI High Throughput screen for identifying small molecule modulators of
alpha-glucosidase for the potential treatment of Pompe disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 4th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 13-15, 2009
CL Las Vegas, NV
SP Lysosomal Dis Network
C1 [Zheng, Wei; Liu, Ke; Southall, Noel; Marugan, Juan; Austin, Christopher] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Motabar, Omid; Goldin, Ehud; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
NR 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2009
VL 96
IS 2
MA 155
BP S46
EP S46
DI 10.1016/j.ymgme.2008.11.156
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 399QG
UT WOS:000262813800163
ER
PT J
AU Fattakhova, GV
Masilamani, M
Narayanan, S
Borrego, F
Gilfillan, AM
Metcalfe, DD
Coligan, JE
AF Fattakhova, Gul'nar V.
Masilamani, Madhan
Narayanan, Sriram
Borrego, Francisco
Gilfillan, Alasdair M.
Metcalfe, Dean D.
Coligan, John E.
TI Endosomal trafficking of the ligated Fc epsilon RI receptor
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Fc epsilon RI; Endosomes; Co-localization; Syk
ID AFFINITY IGE RECEPTOR; MAST-CELL ACTIVATION; IMMUNOGLOBULIN-E; DEPENDENT
ENDOCYTOSIS; MEMBRANE GLYCOPROTEIN; TYROSINE KINASE; PLASMA-MEMBRANE;
GAMMA-SUBUNIT; LIPID RAFTS; SYK
AB In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (Fc epsilon RI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized Fc epsilon RI. Here we demonstrate that in RBL-2H3 cells, aggregated Fc epsilon RI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15 min after ligation, Minimal co-localization of Fc epsilon RI with Rab5 was observed by 30 min, followed by its appearance in the Rab7(+) late endosomes and lysosomes at later time points. During endosomal sorting, Fc epsilon RI alpha and gamma Subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated Fc epsilon RI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of Fc epsilon RI in endosomes. Published by Elsevier Ltd.
C1 [Fattakhova, Gul'nar V.; Masilamani, Madhan; Narayanan, Sriram; Borrego, Francisco; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Gilfillan, Alasdair M.; Metcalfe, Dean D.] NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM jcoligan@niaid.nih.gov
FU Division of Intrainural Research; NIAID/NIH
FX This work was supported by funds from the Division of Intrainural
Research, NIAID/NIH.
NR 49
TC 13
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U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD FEB
PY 2009
VL 46
IS 5
BP 793
EP 802
DI 10.1016/j.molimm.2008.09.002
PG 10
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 415OA
UT WOS:000263942200005
PM 18945491
ER
PT J
AU Barchi, JJ
Kaczmarek, P
AF Barchi, Joseph J., Jr.
Kaczmarek, Piotr
TI Short and Sweet: Evolution of a Small Glycopeptide from a Bladder
Disorder to an Anticancer Lead
SO MOLECULAR INTERVENTIONS
LA English
DT Editorial Material
ID INTERSTITIAL CYSTITIS PATIENTS; ANTIPROLIFERATIVE FACTOR; PROTEINS;
CELLS
C1 [Barchi, Joseph J., Jr.; Kaczmarek, Piotr] NCI, Frederick, MD 21702 USA.
RP Barchi, JJ (reprint author), NCI, 376 Boyles St,POB B, Frederick, MD 21702 USA.
EM barchi@helix.nih.gov
RI Barchi Jr., Joseph/N-3784-2014
NR 16
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 1534-0384
J9 MOL INTERV
JI Mol. Interv.
PD FEB 1
PY 2009
VL 9
IS 1
BP 14
EP 17
DI 10.1124/mi.9.1.5
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 497TA
UT WOS:000270084100002
PM 19299659
ER
PT J
AU Hatfield, DL
Gladyshev, VN
AF Hatfield, Dolph L.
Gladyshev, Vadim N.
TI The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Reveals the Need for Better Understanding of Selenium Biology
SO MOLECULAR INTERVENTIONS
LA English
DT Editorial Material
ID PROSTATE-CANCER; NUTRITIONAL PREVENTION; BETA-CAROTENE; LUNG-CANCER;
SUPPLEMENTATION; RISK; POLYMORPHISM; DEFICIENCY; MORTALITY; MICE
C1 [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
[Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA.
RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM hatfield@mail.nih.gov; vgladyshev1@unl.edu
RI Gladyshev, Vadim/A-9894-2013
FU Intramural NIH HHS [Z01 BC005317-24]; NCI NIH HHS [R01 CA080946, R01
CA080946-09]
NR 24
TC 64
Z9 66
U1 3
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 1534-0384
J9 MOL INTERV
JI Mol. Interv.
PD FEB 1
PY 2009
VL 9
IS 1
BP 18
EP 21
DI 10.1124/mi.9.1.6
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 497TA
UT WOS:000270084100003
PM 19299660
ER
PT J
AU Cadet, J
Krasnova, I
AF Cadet, Jean Lud
Krasnova, Irina N.
TI Cellular and Molecular Neurobiology of Brain Preconditioning
SO MOLECULAR NEUROBIOLOGY
LA English
DT Review
DE Neuronal degeneration; Ischemia; Stroke; Tolerance; Brain
preconditioning
ID OXYGEN-GLUCOSE DEPRIVATION; DELAYED NEURONAL DEATH; NERVE GROWTH-FACTOR;
FOCAL CEREBRAL-ISCHEMIA; ELEMENT-BINDING PROTEIN; TRANSIENT
GLOBAL-ISCHEMIA; HIPPOCAMPAL CA1 REGION; RAT CORTICAL-NEURONS; INDUCIBLE
FACTOR-I; MEDIATED AKT1 ACTIVATION
AB The tolerant brain which is a consequence of adaptation to repeated nonlethal insults is accompanied by the upregulation of protective mechanisms and the downregulation of prodegenerative pathways. During the past 20 years, evidence has accumulated to suggest that protective mechanisms include increased production of chaperones, trophic factors, and other antiapoptotic proteins. In contrast, preconditioning can cause substantial dampening of the organism's metabolic state and decreased expression of proapoptotic proteins. Recent microarray analyses have also helped to document a role of several molecular pathways in the induction of the brain refractory state. The present review highlights some of these findings and suggests that a better understanding of these mechanisms will inform treatment of a number of neuropsychiatric disorders.
C1 [Cadet, Jean Lud; Krasnova, Irina N.] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Cadet, J (reprint author), NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU National Institute on Drug Abuse; NIH; DHHS
FX This paper is supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH, DHHS. The authors also thank the
reviewers whose suggestions helped to improve the paper.
NR 155
TC 31
Z9 35
U1 1
U2 12
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD FEB
PY 2009
VL 39
IS 1
BP 50
EP 61
DI 10.1007/s12035-009-8051-6
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 402OP
UT WOS:000263023300005
PM 19153843
ER
PT J
AU Konno, Y
Kodama, S
Moore, R
Kamiya, N
Negishi, M
AF Konno, Yoshihiro
Kodama, Susumu
Moore, Rick
Kamiya, Nobuhiro
Negishi, Masahiko
TI Nuclear Xenobiotic Receptor Pregnane X Receptor Locks Corepressor
Silencing Mediator for Retinoid and Thyroid Hormone Receptors (SMRT)
onto the CYP24A1 Promoter to Attenuate Vitamin D(3) Activation
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID CONSTITUTIVE ANDROSTANE RECEPTOR; DRUG-INDUCED OSTEOMALACIA; CROSS-TALK;
METABOLISM; EXPRESSION; RIFAMPICIN; ENZYMES; GENES; CAR; SXR
AB We have studied the molecular mechanism by which the nuclear xenobiotic receptors pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR) regulate transcription of the vitamin D(3) 24-hydroxylase (CYP24A1) gene. In the absence of vitamin D(3), PXR activates the CYP24A1 gene by directly binding to and transactivating vitamin D-response elements (VDREs) within its promoter. Vitamin D(3) activates the CYP24A1 promoter by dissociating the corepressor silencing mediator for retinoid and thyroid hormone receptors ( SMRT) from the vitamin D receptor (VDR) on those VDREs. PXR strongly represses vitamin D(3) activation of the CYP24A1 gene, in which PXR indirectly binds to and prevents vitamin D(3)-dependent dissociation of SMRT from the CYP24A1 promoter. The degree of the PXR-mediated locking of SMRT depends on the relative concentration of vitamin D 3 to the human PXR activator rifampicin; SMRT increased its dissociation as this ratio increased. CAR is also found to prevent dissociation of SMRT from the CYP24A1 promoter. Thus, our present study defines the novel molecular mechanism by which PXR and CAR mediate drug interactions with vitamin D 3 to regulate the CYP24A1 gene. Pxr(+/+) and Pxr(-/-) mice were continuously treated with mouse PXR activator PCN to evaluate the hypothesis that induction of the Cyp24a1 gene is responsible for the loss of bone mineral density often observed in patients treated continuously with PXR-activating drugs. PCN-dependent loss of mineral density is observed in the metaphyseal bones of only the Pxr(+/+) mice. This loss, however, does not correlate with the expression levels of the Cyp24a1 gene in these mice.
C1 [Konno, Yoshihiro; Kodama, Susumu; Moore, Rick; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Kamiya, Nobuhiro] NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU Intramural NIH HHS
NR 19
TC 18
Z9 21
U1 1
U2 2
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 FEB
PY 2009
VL 75
IS 2
BP 265
EP 271
DI 10.1124/mol.108.051904
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 396WX
UT WOS:000262623400002
PM 18981260
ER
PT J
AU Caldwell, HK
Stephens, SI
Young, WS
AF Caldwell, H. K.
Stephens, S. I.
Young, W. S., III
TI Oxytocin as a natural antipsychotic: a study using oxytocin knockout
mice
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE psychotomimetics; prepulse inhibition; sensorimotor gating;
schizophrenia; phencyclidine
ID OBSESSIVE-COMPULSIVE DISORDER; STARTLE GATING DEFICITS; PREPULSE
INHIBITION DEFICITS; LOW-DOSE KETAMINE; SCHIZOPHRENIC-PATIENTS; ACOUSTIC
STARTLE; CEREBROSPINAL-FLUID; TOURETTES-SYNDROME; NEUROLEPTIC
MEDICATION; HABITUATION DEFICITS
AB It has been previously suggested that oxytocin (Oxt) may act as a natural antipsychotic. To test this hypothesis, we investigated whether disruption of the oxytocin gene (Oxt-/-) made mice more susceptible to the psychosis-related effects of amphetamine (Amp), apomorphine (Apo) and phencyclidine (PCP). We examined drug-induced changes in the prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating deficits characteristic of several psychiatric and neurological disorders, including schizophrenia. We found that treatment with Amp, Apo and PCP all had effects on PPI. However, in Oxt-/- mice, but not Oxt-/- mice, PCP treatment resulted in large PPI deficits. As PCP is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, these findings suggest that the absence of Oxt alters the glutamatergic component of the PPI.
C1 [Caldwell, H. K.; Stephens, S. I.; Young, W. S., III] NIMH, Sect Neural Gene Express, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Caldwell, HK (reprint author), Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA.
EM wsy@mail.nih.gov
RI Young, W Scott/A-9333-2009
OI Young, W Scott/0000-0001-6614-5112
FU NIMH Intramural Research Program [Z01-MH-002498-17]
FX We thank the NIH Animal Facility in Building 49 for their exceptional
care. We also thank Selen Tolu, James Heath and Emily Shepard for
technical assistance as well as Dr Eric Mintz for his statistical
expertise. This work was supported by the NIMH Intramural Research
Program (Z01-MH-002498-17).
NR 80
TC 60
Z9 61
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD FEB
PY 2009
VL 14
IS 2
BP 190
EP 196
DI 10.1038/sj.mp.4002150
PG 7
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 395VD
UT WOS:000262550700008
PM 18227836
ER
PT J
AU Wang, J
Mansfield, SG
Cote, CA
Du Jiang, P
Weng, K
Amar, MJA
Brewer, BH
Remaley, AT
McGarrity, GJ
Garcia-Blanco, MA
Puttaraju, M
AF Wang, Jun
Mansfield, S. Gary
Cote, Colette A.
Du Jiang, Ping
Weng, Ke
Amar, Marcelo J. A.
Brewer, Bryan H., Jr.
Remaley, Alan T.
McGarrity, Gerard J.
Garcia-Blanco, Mariano A.
Puttaraju, M.
TI Trans-splicing Into Highly Abundant Albumin Transcripts for Production
of Therapeutic Proteins In Vivo
SO MOLECULAR THERAPY
LA English
DT Article
ID APOLIPOPROTEIN-A-I; RNA-POLYMERASE-II; MESSENGER-RNA; HEMOPHILIA-A;
TRANSGENE EXPRESSION; NUCLEOTIDE-SEQUENCE; CYSTIC-FIBROSIS;
SERUM-ALBUMIN; GENE DELIVERY; DNA
AB Spliceosome-mediated RNA trans-splicing has emerged as an exciting mode of RNA therapy. Here we describe a novel trans-splicing strategy, which targets highly abundant pre-mRNAs, to produce therapeutic proteins in vivo. First, we used a pre-trans-splicing molecule (PTM) that mediated trans-splicing of human apolipoprotein A-I (hapoA-I) into the highly abundant mouse albumin exon 1. Hydrodynamic tail vein injection of the hapoA-I PTM plasmid in mice followed by analysis of the chimeric transcripts and protein, confirmed accurate and efficient trans-splicing into albumin pre-mRNA and production of hapoA-I protein. The versatility of this approach was demonstrated by producing functional human papillomavirus type-16 E7 (HPV16-E7) single-chain antibody in C57BL/6 mice and functional factor VIII (FVIII) and phenotypic correction in hemophilia A mice. Altogether, these studies demonstrate that trans-splicing to highly abundant albumin transcripts can be used as a general platform to produce therapeutic proteins in vivo.
C1 [Wang, Jun; Mansfield, S. Gary; Cote, Colette A.; Du Jiang, Ping; Weng, Ke; McGarrity, Gerard J.; Puttaraju, M.] VIRxSYS Corp, Gaithersburg, MD 20877 USA.
[Amar, Marcelo J. A.; Brewer, Bryan H., Jr.; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Garcia-Blanco, Mariano A.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA.
RP Puttaraju, M (reprint author), VIRxSYS Corp, 200 Perry Pkwy,Suite 1A, Gaithersburg, MD 20877 USA.
EM raju@virxsys.com
FU National Heart, Lung, and Blood Institute [R44-HL072687]
FX The hemophilia work was supported in part by a Phase II SBIR grant from
the National Heart, Lung, and Blood Institute ( grant no. R44-HL072687).
We thank Laurent Humeau and Peter Donnelly for critical reading of the
manuscript; John Stonik, Catherine Knapper, Boris Vaisman for assistance
in experimental design and technical help; Lili Portilla for assistance
with the CRADA. The apoA-I research was performed under a CRADA between
NHLBI's Vascular Medicine Branch/Lipoprotein Metabolism Section and
Intronn, Inc. We thank Paul McCray ( University of Iowa) for his advice
on performing the tail clip assay. J.W., S.G.M., P.D.J., G.J.M., and
M.P. are employees of VIRxSYS Corporation (formerly with Intronn, Inc)
and C.A.C. and K. W. were former Intronn, Inc employees.
Spliceosome-mediated RNA trans-splicing technology was developed by
Intronn, Inc., and majority of the work in this article was conducted at
Intronn, Inc. In September 2007, VIRxSYS Corporation acquired all of
Intronn, Inc., assets including intellectual property. M.A.G.-B is a
co-corresponding author in this article and was a co-founder and
consultant to Intronn, Inc., and is currently a consultant to VIRxSYS
Corporation.
NR 45
TC 11
Z9 11
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD FEB
PY 2009
VL 17
IS 2
BP 343
EP 351
DI 10.1038/mt.2008.260
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 406IB
UT WOS:000263287100022
PM 19066600
ER
PT J
AU Guimond, M
Veenstra, RG
Grindler, DJ
Zhang, H
Cui, YZ
Murphy, RD
Kim, SY
Na, RS
Hennighausen, L
Kurtulus, S
Erman, B
Matzinger, P
Merchant, MS
Mackall, CL
AF Guimond, Martin
Veenstra, Rachelle G.
Grindler, David J.
Zhang, Hua
Cui, Yongzhi
Murphy, Ryan D.
Kim, Su Young
Na, Risu
Hennighausen, Lothar
Kurtulus, Sema
Erman, Batu
Matzinger, Polly
Merchant, Melinda S.
Mackall, Crystal L.
TI Interleukin 7 signaling in dendritic cells regulates the homeostatic
proliferation and niche size of CD4(+) T cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; MHC CLASS-II; IN-VIVO; FUNCTIONAL
INTERLEUKIN-7; INTENSIVE CHEMOTHERAPY; DISEASE PROGRESSION; HIV-1
INFECTION; IL-7 INCREASES; POTENTIAL ROLE; STROMAL CELLS
AB Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-alpha-positive (IL-7R alpha(+)) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4(+) T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7R alpha(+) DCs. Our results indicate that IL-7R alpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo.
C1 [Guimond, Martin; Veenstra, Rachelle G.; Grindler, David J.; Zhang, Hua; Cui, Yongzhi; Murphy, Ryan D.; Kim, Su Young; Merchant, Melinda S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Na, Risu; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Erman, Batu] Sabanci Univ, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey.
[Kurtulus, Sema] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Matzinger, Polly] NIAID, Ghost Lab, NIH, Bethesda, MD 20892 USA.
RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM mackallc@mail.nih.gov
FU Intramural Program of the National Cancer Institute
FX We thank V. Kapoor and N. Voong for flow cytometry expertise; M. A.
Caligiuri (Ohio State University) for Flt3 ligand; S. Durum (National
Cancer Institute) for Rag1-/- Il7-/- mice; and S.
Durum, A. Singer and R. Gress for review of the manuscript. Supported by
the Intramural Program of the National Cancer Institute.
NR 48
TC 117
Z9 118
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2009
VL 10
IS 2
BP 149
EP 157
DI 10.1038/ni.1695
PG 9
WC Immunology
SC Immunology
GA 404UM
UT WOS:000263178500008
PM 19136960
ER
PT J
AU Subach, FV
Patterson, GH
Manley, S
Gillette, JM
Lippincott-Schwartz, J
Verkhusha, VV
AF Subach, Fedor V.
Patterson, George H.
Manley, Suliana
Gillette, Jennifer M.
Lippincott-Schwartz, Jennifer
Verkhusha, Vladislav V.
TI Photoactivatable mCherry for high-resolution two-color fluorescence
microscopy
SO NATURE METHODS
LA English
DT Article
ID LOCALIZATION MICROSCOPY; TRANSFERRIN RECEPTOR; MONOMERIC RED;
AMINO-ACID; PROTEIN; NANOSCOPY; CLATHRIN; CELLS; INTERNALIZATION;
CONVERSION
AB The reliance of modern microscopy techniques on photoactivatable fluorescent proteins prompted development of mCherry variants that are initially dark but become red fluorescent after violet-light irradiation. Using ensemble and single-molecule characteristics as selection criteria, we developed PAmCherry1 with excitation/emission maxima at 564/595 nm. Compared to other monomeric red photoactivatable proteins, it has faster maturation, better pH stability, faster photoactivation, higher photoactivation contrast and better photostability. Lack of green fluorescence and single-molecule behavior make monomeric PAmCherry1 a preferred tag for two-color diffraction-limited photoactivation imaging and for super-resolution techniques such as one-and two-color photoactivated localization microscopy (PALM). We performed PALM imaging using PAmCherry1-tagged transferrin receptor expressed alone or with photoactivatable GFP-tagged clathrin light chain. Pair correlation and cluster analyses of the resulting PALM images identified <= 200 nm clusters of transferrin receptor and clathrin light chain at <= 25 nm resolution and confirmed the utility of PAmCherry1 as an intracellular probe.
C1 [Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
[Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10461 USA.
[Subach, Fedor V.; Patterson, George H.; Manley, Suliana; Gillette, Jennifer M.; Lippincott-Schwartz, Jennifer] NICHHD, Sect Organelle Biol, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Verkhusha, VV (reprint author), Albert Einstein Coll Med, Dept Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM vverkhus@aecom.yu.edu
RI Manley, Suliana/D-3818-2012; Subach, Fedor/K-7080-2014
OI Manley, Suliana/0000-0002-4755-4778;
FU US National Institutes of Health [GM070358, GM073913]
FX We thank R. Tsien (University of California at San Diego) for providing
the pRSETBmCherry plasmid, J. Wiedenmann (University of Ulm) for
providing plasmids encoding EosFP variants, J. Zhang for assistance with
flow cytometry, O. Subach for assistance with cell culture and imaging,
and E. Betzig and H. Hess for assistance with PALM experiments, analysis
and discussion. This work was supported by grants GM070358 and GM073913
from the US National Institutes of Health to V. V. V.
NR 30
TC 285
Z9 296
U1 12
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD FEB
PY 2009
VL 6
IS 2
BP 153
EP 159
DI 10.1038/NMETH.1298
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 405CA
UT WOS:000263198500016
PM 19169259
ER
PT J
AU Yang, JM
Siao, CJ
Nagappan, G
Marinic, T
Jing, DQ
McGrath, K
Chen, ZY
Mark, W
Tessarollo, L
Lee, FS
Lu, B
Hempstead, BL
AF Yang, Jianmin
Siao, Chia-Jen
Nagappan, Guhan
Marinic, Tina
Jing, Deqiang
McGrath, Kelly
Chen, Zhe-Yu
Mark, Willie
Tessarollo, Lino
Lee, Francis S.
Lu, Bai
Hempstead, Barbara L.
TI Neuronal release of proBDNF
SO NATURE NEUROSCIENCE
LA English
DT Article
ID NEUROTROPHIC FACTOR; CORTICAL-NEURONS; RAT; BIOSYNTHESIS; ACTIVATION;
EXPRESSION; P75(NTR); SORTILIN; PATHWAY; BDNF
AB Pro-brain-derived neurotrophic factor (proBDNF) and mature BDNF utilize distinct receptors to mediate divergent neuronal actions. Using new tools to quantitate endogenous BDNF isoforms, we found that mouse neurons secrete both proBDNF and mature BDNF. The highest levels of proBDNF and p75 were observed perinatally and declined, but were still detectable, in adulthood. Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and TrkB.
C1 [Yang, Jianmin; Siao, Chia-Jen; Marinic, Tina; McGrath, Kelly; Hempstead, Barbara L.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Jing, Deqiang; Chen, Zhe-Yu; Lee, Francis S.] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA.
[Mark, Willie] Mem Sloan Kettering Canc Ctr, Dept Dev Biol, New York, NY 10065 USA.
[Tessarollo, Lino] NCI, Frederick, MD 21702 USA.
[Nagappan, Guhan; Lu, Bai] NICHHD, Bethesda, MD 20892 USA.
RP Hempstead, BL (reprint author), Weill Cornell Med Coll, Dept Med, 1300 York Ave, New York, NY 10065 USA.
EM blhempst@med.cornell.edu
RI Lu, Bai/A-4018-2012
FU National Institute of Neurological Disorders and Stroke [NS30687,
NS52819]; National 973 Basic Research Program of China [2006CB503803,
2009CB941403]; National Institute of Child Health and Human Development;
National Institute of Mental Health
FX We thank K. Teng and members of the Hempstead laboratory for their
input. These studies were supported by grants from the National
Institute of Neurological Disorders and Stroke (NS30687 to B. L.H. and
NS52819 to F. S. L.), National 973 Basic Research Program of China (No.
2006CB503803 and 2009CB941403 to Z.-Y.C.) and the Intramural Program of
the National Institute of Child Health and Human Development and the
National Institute of Mental Health (to B.L.).
NR 13
TC 177
Z9 185
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD FEB
PY 2009
VL 12
IS 2
BP 113
EP 115
DI 10.1038/nn.2244
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 404VV
UT WOS:000263182000008
PM 19136973
ER
PT J
AU Joksimovic, M
Yun, BA
Kittappa, R
Anderegg, AM
WChang, W
Taketo, MM
McKay, RDG
Awatramani, RB
AF Joksimovic, Milan
Yun, Beth A.
Kittappa, Raja
Anderegg, Angela M.
WChang, Wendy
Taketo, Makoto M.
McKay, Ronald D. G.
Awatramani, Rajeshwar B.
TI Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis
SO NATURE NEUROSCIENCE
LA English
DT Article
ID BETA-CATENIN GENE; SONIC-HEDGEHOG; DOPAMINERGIC-NEURONS; EXPRESSION;
CELLS; FATE; PROGENITORS; BRAIN; IDENTIFICATION; FOREBRAIN
AB The floor plate, an essential ventral midline organizing center that produces the morphogen Shh, has distinct properties along the neuraxis. The neurogenic potential of the floor plate and its underlying mechanisms remain unknown. Using Shh as a driver for lineage analysis, we found that the mouse midbrain, but not the hindbrain, floor plate is neurogenic, giving rise to dopamine (DA) neurons. Distinct spatiotemporal Shh and Wnt expression may distinguish the neurogenetic potential of these structures. We discovered an inhibitory role for Shh: removal of Shh resulted in neurogenesis from the hindbrain midline and, conversely, high doses of Shh inhibited proliferation and DA neuron production in midbrain cultures. We found that Wnt/beta-catenin signaling is necessary and sufficient for antagonizing Shh, DA progenitor marker induction and promotion of dopaminergic neurogenesis. These findings demonstrate how the dynamic interplay of canonical Wnt/beta-catenin signaling and Shh may orchestrate floor plate neurogenesis or a lack thereof.
C1 [Joksimovic, Milan; Yun, Beth A.; Anderegg, Angela M.; Awatramani, Rajeshwar B.] Northwestern Univ, Feinberg Med Sch, Dept Neurol, Chicago, IL 60611 USA.
[Joksimovic, Milan; Yun, Beth A.; Anderegg, Angela M.; Awatramani, Rajeshwar B.] Northwestern Univ, Feinberg Med Sch, Ctr Genet Med, Chicago, IL 60611 USA.
[Kittappa, Raja; WChang, Wendy; McKay, Ronald D. G.] NINDS, Mol Biol Lab, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan.
RP Awatramani, RB (reprint author), Northwestern Univ, Feinberg Med Sch, Dept Neurol, 7-113 Lurie Bldg,303 Super St, Chicago, IL 60611 USA.
EM r-awatramani@northwestern.edu
RI Joksimovic, Milan/A-4952-2016
OI Joksimovic, Milan/0000-0002-3936-4632
FU Dana Foundation; American Parkinson's Disease Association; Parkinson's
Disease Foundation
FX We thank C. Tabin for Shh::cre mice and Shh cDNA; M. German for antibody
to Lmx1a; T. Muller and C. Birchmeier for antibody to Lmx1b; D. Anderson
for antibody to Ngn2; T. Edlund for antibodies to Gbx2; and A. Klar for
the Spon1l cDNA. We thank A. Chenn for supplying Ctnnb1 mouse strains.
We thank J. Kessler for suggestions. R. B. A was supported by the Dana
Foundation and the American Parkinson's Disease Association. M. J. was
supported by the Parkinson's Disease Foundation.
NR 37
TC 105
Z9 107
U1 0
U2 7
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 FEB
PY 2009
VL 12
IS 2
BP 125
EP 131
DI 10.1038/nn.2243
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 404VV
UT WOS:000263182000012
PM 19122665
ER
PT J
AU Finkel, T
AF Finkel, Toren
TI WHERE'S WALDO FOR AUTOPHAGOSOMES
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Editorial Material
ID MATURATION; NIX
C1 NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD FEB
PY 2009
VL 10
IS 2
BP 89
EP 89
DI 10.1038/nrm2603
PG 1
WC Cell Biology
SC Cell Biology
GA 404US
UT WOS:000263179100008
ER
PT J
AU Li, L
Dutra, A
Pak, E
Labrie, JE
Gerstein, RM
Pandolfi, PP
Recht, LD
Ross, AH
AF Li, Li
Dutra, Amalia
Pak, Evgenia
Labrie, Joseph E., III
Gerstein, Rachel M.
Pandolfi, Pier Paolo
Recht, Larry D.
Ross, Alonzo H.
TI EGFRvIII expression and PTEN loss synergistically induce chromosomal
instability and glial tumors
SO NEURO-ONCOLOGY
LA English
DT Article
DE aneuploidy; EGFRvIII; glioblastoma; neural precursor cells; PTEN
ID GROWTH-FACTOR RECEPTOR; NEURAL STEM-CELL; HUMAN BRAIN-TUMORS;
GLIOBLASTOMA-MULTIFORME; SELF-RENEWAL; DNA-DAMAGE; PHOSPHATIDYLINOSITOL
3-KINASE; CONSTITUTIVE ACTIVATION; GENETIC INSTABILITY;
SIGNAL-TRANSDUCTION
AB Glioblastomas often show activation of epidermal growth factor receptor (EGFR) and loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor, but it is not known if these two genetic lesions act together to transform cells. To answer this question, we infected PTEN-/-neural precursor cells with a retrovirus encoding EGFRvIII, which is a constitutively activated receptor. EGFRvIII PTEN-/-cells formed highly mitotic tumors with nuclear pleomorphism, necrotic areas, and glioblastoma markers. The transformed cells showed increased cell proliferation, centrosome amplification, colony formation in soft agar, self-renewal, expression of the stem cell marker CD133, and resistance to oxidative stress and ionizing radiation. The RAS/mitogen-activated protein kinase (ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways were activated, and checkpoint kinase 1 (Chk1), the DNA damage regulator, was phosphorylated at S280 by Akt, suppressing Chk1 phosphorylation at S345 in response to ionizing irradiation. The PTEN-/-cells showed low levels of DNA damage in the absence of irradiation, which was increased by EGFRvIII expression. Finally, secondary changes occurred during tumor growth in mice. Cells from these tumors showed decreased tumor latencies and additional chromosomal aberrations. Most of these tumor lines showed translocations of mouse chromosome 15. Intracranial injections of one of these lines led to invasive, glial fibrillary acidic protein-positive, nestin-positive tumors. These results provide a molecular basis for the occurrence of these two genetic lesions in brain tumors and point to a role in induction of genomic instability. Neuro-Oncology 11, 9-21, 2009 (Posted to Neuro-Oncology [serial online], Doc. D07-00253, September 23, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-081)
C1 [Li, Li; Ross, Alonzo H.] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA.
[Labrie, Joseph E., III; Gerstein, Rachel M.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01605 USA.
[Dutra, Amalia; Pak, Evgenia] NHGRI, NIH, Bethesda, MD 20892 USA.
[Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Dept Pathol, Program Canc Genet, Boston, MA 02215 USA.
[Recht, Larry D.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Palo Alto, CA USA.
RP Ross, AH (reprint author), Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, 364 Plantat St, Worcester, MA 01605 USA.
EM Alonzo.Ross@umassmed.edu
FU NIH [NS21716]; Human Genome Research Institute; Goldhirsh Foundation;
Worcester Foundation
FX This work was supported in part by NIH NS21716, the Intramural Program
of the Human Genome Research Institute, the Goldhirsh Foundation, and
the Worcester Foundation.
NR 71
TC 50
Z9 52
U1 0
U2 0
PU DUKE UNIV PRESS
PI DURHAM
PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD FEB
PY 2009
VL 11
IS 1
BP 9
EP 21
DI 10.1215/15228517-2008-081
PG 13
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 406LK
UT WOS:000263296800003
PM 18812521
ER
PT J
AU McCallion, AS
Pavan, WJ
Chakravarti, A
Johnson, S
Antonellis, A
Huynh, JL
Stine, ZE
McGaughey, D
Gorkin, D
Prasad, MK
Emison, ES
Loftus, SK
AF McCallion, A. S.
Pavan, W. J.
Chakravarti, A.
Johnson, S.
Antonellis, A.
Huynh, J. L.
Stine, Z. E.
McGaughey, D. M.
Gorkin, D.
Prasad, M. K.
Emison, E. S.
Loftus, S. K.
TI Identification of mammalian neural crest enhancers through transgenesis
in Zebrafish
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [McCallion, A. S.; Chakravarti, A.; Huynh, J. L.; Stine, Z. E.; McGaughey, D. M.; Gorkin, D.; Prasad, M. K.; Emison, E. S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Pavan, W. J.; Antonellis, A.; Loftus, S. K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Johnson, S.] Washington Univ, St Louis, MO USA.
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 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD FEB
PY 2009
VL 21
IS 2
BP IX
EP IX
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 397UT
UT WOS:000262688300043
ER
PT J
AU Pavan, WJ
Watkins-Chow, DE
Matera, I
Buac, K
Larson, D
Loftus, SK
Hou, L
Incao, A
Silver, DL
Rivas, C
Elliott, EC
Baxter, LL
AF Pavan, W. J.
Watkins-Chow, D. E.
Matera, I.
Buac, K.
Larson, D.
Loftus, S. K.
Hou, L.
Incao, A.
Silver, D. L.
Rivas, C.
Elliott, E. C.
Baxter, L. L.
TI A sensitized mouse mutagenesis screen for modifiers of Sox10
neurocristopathies
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Pavan, W. J.; Watkins-Chow, D. E.; Matera, I.; Buac, K.; Larson, D.; Loftus, S. K.; Hou, L.; Incao, A.; Silver, D. L.; Rivas, C.; Elliott, E. C.; Baxter, L. L.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD FEB
PY 2009
VL 21
IS 2
BP XXV
EP XXV
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 397UT
UT WOS:000262688300103
ER
PT J
AU Sumner, JP
Shapiro, EM
Maric, D
Conroy, R
Koretsky, AP
AF Sumner, James P.
Shapiro, Erik M.
Maric, Dragan
Conroy, Richard
Koretsky, Alan P.
TI In vivo labeling of adult neural progenitors for MRI with micron sized
particles of iron oxide: Quantification of labeled cell phenotype
SO NEUROIMAGE
LA English
DT Article
ID POSTNATAL RAT FOREBRAIN; SUBVENTRICULAR ZONE; OLFACTORY-BULB; NEURONAL
MIGRATION; MAMMALIAN BRAIN; GENERATED NEURONS; RODENT BRAIN; STEM;
OLIGODENDROCYTES; ASTROCYTES
AB The subventricular zone (SVZ) is a continual source of neural progenitors throughout adulthood. Many of the animal models designed to study the migration of these cells from the ventricle to places of interest like the olfactory bulb or an injury site require histology to localize precursor cells. Here, it is demonstrated that up to 30% of the neural progenitors that migrate along the rostral migratory stream (RMS) in an adult rodent can be labeled for MRI via intraventricular injection of micron sized particles of iron oxide (MPIOs). The precursors migrating from the SVZ along the RMS were found to populate the olfactory bulb with all three types of neural cells; neurons, oligodendrocytes, and astrocytes. In all cases 10-30% of these cells were labeled in the RMS en route to the olfactory bulb. Ara- C, an anti- mitotic agent, eliminated precursor cells at the SVZ, RMS, and olfactory bulb and also eliminated the MRI detection of the precursors. This indicates that the MRI signal detected is due to progenitor cells that leave the SVZ and is not due to nonspeci. c diffusion of MPIOs. Using MRI to visualize neural progenitor cell behavior in individual animals during plasticity or disease models should be a useful tool, especially in combination with other information that MRI can supply. Published by Elsevier Inc.
C1 [Sumner, James P.; Conroy, Richard; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Shapiro, Erik M.] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA.
[Maric, Dragan] NINDS, FACS Facil, Bethesda, MD 20892 USA.
[Conroy, Richard] Natl Inst Stand & Technol, Boulder, CO USA.
RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bldg 10,Room B1D728,10 Ctr Dr,MSC 1065, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Conroy, Richard/D-1979-2009; Koretsky, Alan/C-7940-2015
OI Conroy, Richard/0000-0002-8896-6090; Koretsky, Alan/0000-0002-8085-4756
FU NINDS Intramural Research Program; NIH
FX This research was supported by the NINDS Intramural Research Program of
NIH. We thank N. Bouraoud and S. Dodd, for their technical assistance
with animal surgeries and MRI, respectively. We also thank Carolyn Smith
for use of the NINDS Light Imaging Facility.
NR 34
TC 49
Z9 54
U1 0
U2 7
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 FEB 1
PY 2009
VL 44
IS 3
BP 671
EP 678
DI 10.1016/j.neuroimage.2008.07.050
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KL
UT WOS:000262301500008
PM 18722534
ER
PT J
AU Saad, ZS
Glen, DR
Chen, G
Beauchamp, MS
Desai, R
Cox, RW
AF Saad, Ziad S.
Glen, Daniel R.
Chen, Gang
Beauchamp, Michael S.
Desai, Rutvik
Cox, Robert W.
TI A new method for improving functional-to-structural MRI alignment using
local Pearson correlation
SO NEUROIMAGE
LA English
DT Article
ID SURFACE-BASED ANALYSIS; IMAGE REGISTRATION; CEREBRAL-CORTEX; BRAIN
IMAGES; ROBUST; OPTIMIZATION; SOFTWARE; LANGUAGE; GRADIENT
AB Accurate registration of Functional Magnetic Resonance Imaging (FMRI) T2*-weighted volumes to sames-subject high-resolution T1-weighted structural volumes is important for Blood Oxygenation Level Dependent (BOLD) FMRI and crucial for applications such as cortical surface-based analyses and pre-surgical planning. Such registration is generally implemented by minimizing a cost functional, which measures the mismatch between two image volumes over the group of proper affine transformations. Widely used cost functionals, such as mutual information (MI) and correlation ratio (CR), appear to yield decent alignments when visually judged by matching outer brain contours. However, close inspection reveals that internal brain structures are often significantly misaligned. Poor registration is most evident in the ventricles and sulcal folds, where CSF is concentrated. This observation motivated our development of an improved modality-specific cost functional which uses a weighted local Pearson coefficient (LPC) to align T2*-and T1-weighted images. In the absence of an alignment gold standard, we used three human observers blinded to registration method to provide an independent assessment of the quality of the registration for each cost functional. We found that LPC performed significantly better (p<0.001) than generic cost functionals including MI and CR. Generic cost functionals were very often not minimal near the best alignment, thereby suggesting that optimization is not the cause of their failure. Lastly, we emphasize the importance of precise visual inspection of alignment quality and present an automated method for generating composite images that help capture errors of misalignment. Published by Elsevier Inc.
C1 [Saad, Ziad S.; Glen, Daniel R.; Chen, Gang; Cox, Robert W.] NIMH, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Beauchamp, Michael S.] Univ Texas Hlth Sci Ctr Houston, Dept Neurobiol & Anat, Houston, TX USA.
[Desai, Rutvik] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
RP Cox, RW (reprint author), NIMH, NIH, US Dept HHS, 10 Ctr Dr,Room 1D80, Bethesda, MD 20892 USA.
EM rwcox@nih.gov
OI Beauchamp, Michael/0000-0002-7599-9934
FU NIMH; NINDS Intramural Programs; NIH; MSB; NSF [0642532]; NIH/NIDCD
[5R03DC008416-02, 2R01NS33576-11]
FX This research was supported by the NIMH and NINDS Intramural Programs of
the NIH. MSB was supported by NSF grant 0642532 (PI Michael Beauchamp);
RD was supported by NIH/NIDCD grant 5R03DC008416-02 (PI Rutvik Desai)
and NIH/ NINDS grant 2R01NS33576- 11 (PI Jeffery Binder).
NR 29
TC 165
Z9 166
U1 3
U2 9
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 FEB 1
PY 2009
VL 44
IS 3
BP 839
EP 848
DI 10.1016/j.neuroimage.2008.09.037
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KL
UT WOS:000262301500024
PM 18976717
ER
PT J
AU Murphy, K
Birn, RM
Handwerker, DA
Jones, TB
Bandettini, PA
AF Murphy, Kevin
Birn, Rasmus M.
Handwerker, Daniel A.
Jones, Tyler B.
Bandettini, Peter A.
TI The impact of global signal regression on resting state correlations:
Are anti-correlated networks introduced?
SO NEUROIMAGE
LA English
DT Article
ID INDEPENDENT COMPONENT ANALYSIS; BOLD HEMODYNAMIC-RESPONSES; DEFAULT-MODE
NETWORK; CEREBRAL-BLOOD-FLOW; FUNCTIONAL MRI; HUMAN BRAIN; FMRI DATA;
EMPIRICAL ANALYSES; NULL-HYPOTHESIS; LOCAL CHANGES
AB Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step. (C) 2008 Published by Elsevier Inc.
C1 [Bandettini, Peter A.] NIMH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, Bethesda, MD 20892 USA.
RP Bandettini, PA (reprint author), NIMH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bldg 10,Room 1D80B,10 Ctr Dr MSC 1148, Bethesda, MD 20892 USA.
EM bandettini@nih.gov
RI Murphy, Kevin/A-1581-2010
OI Murphy, Kevin/0000-0002-6516-313X
FU Intramural Research Program; National Institute of Mental Health; NIH
FX This study was supported by the Intramural Research Program, National
Institute of Mental Health, NIH. Thanks go to Phil Reiss and Clare Kelly
for helpful discussions.
NR 63
TC 851
Z9 858
U1 4
U2 43
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 FEB 1
PY 2009
VL 44
IS 3
BP 893
EP 905
DI 10.1016/j.neuroimage.2008.09.036
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KL
UT WOS:000262301500029
PM 18976716
ER
PT J
AU Tucciarone, J
Chuang, KH
Dodd, SJ
Silva, A
Pelled, G
Koretsky, AP
AF Tucciarone, Jason
Chuang, Kai-Hsiang
Dodd, Steven J.
Silva, Afonso
Pelled, Galit
Koretsky, Alan P.
TI Layer specific tracing of corticocortical and thalamocortical
connectivity in the rodent using manganese enhanced MRI
SO NEUROIMAGE
LA English
DT Article
ID RESONANCE-IMAGING MEMRI; SOMATIC SENSORY CORTEX; IN-VIVO; SOMATOSENSORY
CORTEX; BRAIN ACTIVITY; MOUSE-BRAIN; RAT; ORGANIZATION; CONTRAST; MODEL
AB Information about layer specific connections in the brain comes mainly from classical neuronal tracers that rely on histology. Manganese Enhanced MRI (MEMRI) has mapped connectivity along a number of brain pathways in several animal models. It is not clear at what level of specificity neuronal connectivity measured using MEMRI tracing can resolve. The goal of this work was to determine if neural tracing using MEMRI could distinguish layer inputs of major pathways of the cortex. To accomplish this, tracing was performed between hemispheres of the somatosensory (S1) cortex and between the thalamus and S1 cortex. T(1) mapping and T(1) weighted pulse sequences detected layer specific tracing after local injection of MnCl(2). Approximately 12 h following injections into S1 cortex, maximal T(1) reductions were observed at 0.6 +/- 0.07 and 1.1 +/- 0.12 mm from the brain surface in the contralateral S1. These distances correspond to the positions of layer 3 and 5 consistent with the known callosal inputs along this pathway. Four to six hours following injection of MnCl2 into the thalamus there were maximal T(1) reductions between 0.7 +/- 0.08 and 0.8 +/- 0.08 mm from the surface of the brain, which corresponds to layer 4. This is consistent with terminations of the known thalamocortical projections. In order to observe the first synapse projection, it was critical to perform MRI at the right time after injections to detect layer specificity with MEMRI. At later time points, tracing through the cortical network led to more uniform contrast throughout the cortex due to its complex neuronal connections. These results are consistent with well established neuronal pathways within the somatosensory cortex and demonstrate that layer specific somatosensory connections can be detected in vivo using MEMRI. Published by Elsevier Inc.
C1 [Tucciarone, Jason; Chuang, Kai-Hsiang; Dodd, Steven J.; Silva, Afonso; Pelled, Galit; Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Koretsky, AP (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,B1D728, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015;
OI Koretsky, Alan/0000-0002-8085-4756; Chuang,
Kai-Hsiang/0000-0002-8356-0657
FU NINDS; NIH
FX The authors would like to acknowledge the surgical assistance and
expertise of Ms. Nadia Bouraoud and Ms. Kathy Sharer. This research was
supported by the Intramural Research Program of the NINDS, NIH.
NR 49
TC 29
Z9 32
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 FEB 1
PY 2009
VL 44
IS 3
BP 923
EP 931
DI 10.1016/j.neuroimage.2008.07.036
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KL
UT WOS:000262301500032
PM 18755280
ER
PT J
AU Mooshagian, E
Iacoboni, M
Zaidel, E
AF Mooshagian, Eric
Iacoboni, Marco
Zaidel, Eran
TI Spatial attention and interhemispheric visuomotor integration in the
absence of the corpus callosum
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Reaction time; Poffenberger paradigm; Interhemispheric transfer; Task
context; Split brain; CUD; Laterality
ID SIMPLE REACTION-TIMES; LATERALIZED LEXICAL DECISION; CROSSED-UNCROSSED
DIFFERENCE; S-R COMPATIBILITY; SPLIT-BRAIN; ANATOMICAL FACTORS; LIGHT
STIMULI; LONG-TERM; FLASHES; CALLOSOTOMY
AB In the lateralized simple reaction time (SRT) task with unimanual responses (Poffenberger paradigm), reaction times (RTs) are faster with ipsilateral (uncrossed) than with contralateral (crossed) response hand-target hemifield combinations. The difference between crossed and uncrossed responses (CUD) has typically been interpreted to reflect callosal transfer time. Indeed, acallosal subjects and split-brain subjects have longer CUDs than control subjects. However, a few recent studies have demonstrated that, contrary to classical findings, the CUD is also affected by non-anatomical factors. Here we show that the CUD is also affected by non-anatomical factors in patients with agenesis of the corpus callosum and complete commissurotomy where interhemispheric transfer must be subcallosal. We tested acallosal subject M.M. and split brain patient A.A. on a lateralized SRT task with their arms alternately uncrossed (natural arms position) or crossed (unnatural arms position) across blocks of trials. The results revealed a significant effect of arms crossing on the size and direction of the CUD as previously found in normal subjects [Mooshagian, E., lacoboni, M., & Zaidel, E. (2008). The role of task history in simple reaction time to lateralized light flashes. Neuropsychologia, 46(2), 659-664]. This suggests that non-anatomical factors that modulate interhemispheric visuomotor integration may occur in absence of the corpus callosum. Anterior commissure and interhemispheric cortico-subcortical pathways are likely implicated in these effects. (C) Published by Elsevier Ltd.
C1 [Mooshagian, Eric; Zaidel, Eran] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Iacoboni, Marco; Zaidel, Eran] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
[Iacoboni, Marco] Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst,Ahmanson Lovelace Brain Mappin, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Mooshagian, E (reprint author), Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, NIH, MSC 1440,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mooshage@ninds.nih.gov
FU National Institutes of Health [NIH NS-20187]
FX We thank A.A. and M.M. for their participation in the experiments,
Aakash Kishore for assistance with data analysis, and three anonymous
reviewers for comments on a previous draft of the manuscript. This work
was supported by a grant from the National Institutes of Health (NIH
NS-20187).
NR 30
TC 10
Z9 10
U1 2
U2 3
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 FEB
PY 2009
VL 47
IS 3
BP 933
EP 937
DI 10.1016/j.neuropsychologia.2008.12.005
PG 5
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 419RP
UT WOS:000264237300036
PM 19124029
ER
PT J
AU Schmidt, PJ
Steinberg, EM
Negro, PP
Haq, N
Gibson, C
Rubinow, DR
AF Schmidt, Peter J.
Steinberg, Emma M.
Negro, Paula Palladino
Haq, Nazli
Gibson, Carolyn
Rubinow, David R.
TI Pharmacologically Induced Hypogonadism and Sexual Function in Healthy
Young Women and Men
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE sexual function; hypogonadism; estradiol; progesterone; testosterone;
GnRH agonist
ID PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; ESTROGEN REPLACEMENT THERAPY;
SURGICALLY MENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; MENSTRUAL-CYCLE;
DOUBLE-BLIND; AGING MEN; PREMENOPAUSAL WOMEN; TESTOSTERONE LEVELS
AB Studies fail to find uniform effects of age-related or induced hypogonadism on human sexual function. We examined the effects of induced hypogonadism on sexual function in healthy men and women and attempted to identify predictors of the sexual response to induced hypogonadism or hormone addback. The study design used was a double-blind, controlled, crossover (self-as-own control). The study setting was an ambulatory care clinic in a research hospital, and the participants were 20 men (average +/- SD age 28.5 +/- 6.2 years) and 20 women (average +/- SD age 33.5 +/- 8.7 years), all healthy and with no history of psychiatric illness. A multidimensional scale assessing several domains of sexual function was the main outcome measure. Participants of the study received depot leuprolide acetate (Lupron) every 4 weeks for 3 months (men) or 5 months (women). After the first month of Lupron alone, men received (in addition to Lupron) testosterone enanthate (200 mg intramuscularly) or placebo every 2 weeks for 1 month each. Women received Lupron alone for 2 months, and then, in addition to Lupron, they received estradiol and progesterone for 5 weeks each. The results of the study: in women, hypogonadism resulted in a significant decrease in global measures of sexual functioning, principally reflecting a significant decrease in the reported quality of orgasm. In men, hypogonadism resulted in significant reductions in all measured domains of sexual function. Testosterone restored sexual functioning scores in men to those seen at baseline, whereas neither estradiol nor progesterone significantly improved the reduced sexual functioning associated with hypogonadism in women. Induced hypogonadism decreased sexual function in a similar number of men and women. No predictors of response were identified except for levels of sexual function at baseline. In conclusion, our data do not support a simple deficiency model for the role of gonadal steroids in human sexual function; moreover, while variable, the role of testosterone in sexual function in men is more apparent than that of estradiol or progesterone in women.
C1 [Schmidt, Peter J.; Steinberg, Emma M.; Negro, Paula Palladino; Haq, Nazli; Gibson, Carolyn] Natl Inst Mental Hlth, Behav Endocrinol Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Schmidt, PJ (reprint author), Natl Inst Mental Hlth, Behav Endocrinol Branch, NIH, DHHS, Bldg 10 CRC,Room 6-5340,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA.
EM peterschmidt@mail.nih.gov
FU National Institute of Mental Health's Intramural Research Program
FX This work was supported by the National Institute of Mental Health's
Intramural Research Program. Dr Schmidt had full access to all of the
data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis. Other authors have nothing to
disclose.
NR 103
TC 20
Z9 20
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2009
VL 34
IS 3
BP 565
EP 576
DI 10.1038/npp.2008.24
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 393MA
UT WOS:000262376200005
PM 18354393
ER
PT J
AU Cheeran, B
Cohen, L
Dobkin, B
Ford, G
Greenwood, R
Howard, D
Husain, M
Macleod, M
Nudo, R
Rothwell, J
Rudd, A
Teo, J
Ward, N
Wolf, S
AF Cheeran, Binith
Cohen, Leonardo
Dobkin, Bruce
Ford, Gary
Greenwood, Richard
Howard, David
Husain, Masud
Macleod, Malcolm
Nudo, Randolph
Rothwell, John
Rudd, Anthony
Teo, James
Ward, Nicholas
Wolf, Steven
CA Cumberland Consensus Working Grp
TI The Future of Restorative Neurosciences in Stroke: Driving the
Translational Research Pipeline From Basic Science to Rehabilitation of
People After Stroke
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE Rehabilitation; Research pipeline; Translation
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; RECOVERY FOLLOWING STROKE;
EARLY SUPPORTED DISCHARGE; MOTOR CORTEX STIMULATION; EAST MELBOURNE
STROKE; CORTICAL STIMULATION; BRAIN-INJURY; PROMOTES RECOVERY;
OCCUPATIONAL-THERAPY
AB Background. Major advances during the past 50 years highlight the immense potential for restoration of function after neural injury, even in the damaged adult human brain. Yet, the translation of these advances into clinically useful treatments is painstakingly slow. Objective. Here, we consider why the traditional model of a "translational research pipeline" that transforms basic science into novel clinical practice has failed to improve rehabilitation practice for people after stroke. Results. We find that (1) most treatments trialed in vitro and in animal models have not yet resulted in obviously useful functional gains in patients; (2) most clinical trials of restorative treatments after stroke have been limited to small-scale studies; (3) patient recruitment for larger clinical trials is difficult; (4) the determinants of patient outcomes and what patients want remain complex and ill-defined, so that basic scientists have no clear view of the clinical importance of the problems that they are addressing; (5) research in academic neuroscience centers is poorly integrated with practice in front-line hospitals and the community, where the majority of patients are treated; and (6) partnership with both industry stakeholders and patient pressure groups is poorly developed, at least in the United Kingdom where research in the translational restorative neurosciences in stroke depends on public sector research funds and private charities. Conclusions. We argue that interaction between patients, front-line clinicians, and clinical and basic scientists is essential so that they can explore their different priorities, skills, and concerns. These interactions can be facilitated by funding research consortia that include basic and clinical scientists, clinicians and patient/carer representatives with funds targeted at those impairments that are major determinants of patient and carer outcomes. Consortia would be instrumental in developing a lexicon of common methods, standardized outcome measures, data sharing and long-term goals. Interactions of this sort would create a research-friendly, rather than only target-led, culture in front-line stroke rehabilitation services.
C1 [Greenwood, Richard; Husain, Masud] Natl Hosp Neurol & Neurosurg, Inst Neurol, London WC1N 3BG, England.
[Cheeran, Binith; Greenwood, Richard; Rothwell, John; Teo, James; Ward, Nicholas] Inst Neurol, Sobell Dept Motor Neurosci, London WC1N 3BG, England.
[Ward, Nicholas] Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
[Dobkin, Bruce] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Cohen, Leonardo] NINDS, NIH, Bethesda, MD 20892 USA.
[Nudo, Randolph] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA.
[Wolf, Steven] Emory Univ, Atlanta, GA 30322 USA.
[Macleod, Malcolm] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Rudd, Anthony] Kings Coll London, London, England.
[Ford, Gary; Howard, David] Univ Newcastle, Callaghan, NSW 2308, Australia.
[Husain, Masud] UCL, Inst Cognit Neurosci, London WC1E 6BT, England.
RP Greenwood, R (reprint author), Natl Hosp Neurol & Neurosurg, Inst Neurol, Queen Sq, London WC1N 3BG, England.
EM richard.greenwood@uclh.nhs.uk
RI Nudo, Randolph/B-1623-2009; Macleod, Malcolm/B-2052-2010; Ford,
Gary/A-6353-2012; Husain, Masud/C-2074-2008; van Vliet,
Paulette/F-4616-2010; Teo, James/D-9696-2011;
OI Macleod, Malcolm Robert/0000-0001-9187-9839; Husain,
Masud/0000-0002-6850-9255; Teo, James/0000-0002-6899-8319; Howard,
David/0000-0001-9141-5751; Burridge, Jane/0000-0003-3497-6725; Teo,
Jeanette/0000-0002-9321-3341; Rothwell, John/0000-0003-1367-6467;
Cheeran, Binith/0000-0002-3442-1044
NR 99
TC 67
Z9 67
U1 3
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD FEB
PY 2009
VL 23
IS 2
BP 97
EP 107
DI 10.1177/1545968308326636
PG 11
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 401OG
UT WOS:000262949900001
ER
PT J
AU Cai, Q
Sheng, ZH
AF Cai, Qian
Sheng, Zu-Hang
TI Molecular Motors and Synaptic Assembly
SO NEUROSCIENTIST
LA English
DT Article
DE synaptogenesis; synaptic plasticity; kinesin; myosin; motor adaptor;
axonal transport
ID KINESIN SUPERFAMILY MOTOR; AMPA RECEPTOR TRAFFICKING; AXONAL-TRANSPORT;
HIPPOCAMPAL-NEURONS; VESICLE TRANSPORT; HEAVY-CHAIN; MYOSIN-V;
INTRACELLULAR-TRANSPORT; NEUROMUSCULAR-JUNCTION; CYTOPLASMIC DYNEIN
AB Proper synaptic function requires the seamless integration of the transport, assembly, and regulation of synaptic components and structures. Inasmuch as the synapse is often distant from the neuronal cell body, newly synthesized synaptic proteins, the precursors of synaptic vesicles, active zone compartments, channels and receptors, and mitochondria, must be transported along lengthy neuronal processes to participate in synaptogenesis. Neuronal transport is mediated by motor proteins that associate with their cargoes via adaptors ( or receptors) and that travel along the cytoskeleton network within the neuronal processes. Thus, the identity of membranous protein cargoes and the specificity of motor-cargo interactions are critical for correctly targeting cargoes and properly assembling synapses in developing neurons and in remodeling synapses of mature neurons in response to neuronal activity. In this article, the authors review recent progress in characterizing microtubule- and actin-based motor proteins that are involved in delivering synaptic components and discuss potential mechanisms underlying the formation of motor-receptor-cargo complexes that contribute to synaptogenesis and activity-induced synaptic plasticity.
C1 [Cai, Qian; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 3B203,35 Convent Dr, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU Intramural Research Program of NINDS; NIH
FX The authors thank the members of the Sheng lab for helpful discussions,
and D. Glazer-Schoenberg and A. Simone for editing. This work was
supported by the Intramural Research Program of NINDS, NIH (Z-HS).
NR 69
TC 15
Z9 16
U1 0
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-8584
J9 NEUROSCIENTIST
JI Neuroscientist
PD FEB
PY 2009
VL 15
IS 1
BP 78
EP 89
DI 10.1177/1073858408329511
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 407LG
UT WOS:000263364000014
PM 19218232
ER
PT J
AU Hazin, R
Cadet, J
Kahook, M
Saed, D
AF Hazin, Ribhi
Cadet, Jean Lud
Kahook, Malik Y.
Saed, Dunia
TI Ocular Manifestations of Crystal Methamphetamine Use
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Crystal methamphetamine; Meth abuse; Neurotoxicity; Ocular injury;
Ocular development
ID RAT RETINA; DRUG-ABUSE; INFANT DEVELOPMENT; PRENATAL EXPOSURE; PHOSPHINE
GAS; LIFE-STYLE; COCAINE; AMPHETAMINE; ENVIRONMENT; INHALATION
AB Numerous medical sequelae associated with illicit drug use have been reported. Nevertheless, there has been scarce documentation of the effects of these drugs on the eyes. Drug-induced ocular symptoms include decreased visual acuity, disturbances in perception, and even flashbacks. Methamphetamine (METH) is a highly addictive drug whose abuse has spread worldwide during the past two decades. METH abuse is associated with many adverse psychiatric and medical consequences including strokes and psychosis. METH-induced ophthalmic complications are rarely discussed but include retinal vasculitis, episcleritis, panophthalmitis, endophthalmitis, scleritis, retinopathy, corneal ulceration, and transient visual losses. Because the drug has shown a marked increase in the prevalence of its use amongst pregnant women, there has also been an increase of drug-induced complications in fetuses and newborn babies. These complications need to be further detailed and studied. Herein, the authors report on the ocular complications associated with METH abuse. They also discuss some potential mechanisms for the toxic effects of the drug on that system.
C1 [Hazin, Ribhi] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA.
[Hazin, Ribhi; Saed, Dunia] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Ophthalmol & Visual Sci, Omaha, NE 68198 USA.
[Cadet, Jean Lud] NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Kahook, Malik Y.] Univ Colorado, Sch Med, Rocky Mt Lions Eye Inst, Aurora, CO 80045 USA.
RP Hazin, R (reprint author), Harvard Univ, Fac Arts & Sci, 219 Garden St,Suite 214, Cambridge, MA 02138 USA.
EM Hazin@fas.harvard.edu
NR 36
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD FEB
PY 2009
VL 15
IS 2
BP 187
EP 191
DI 10.1007/s12640-009-9019-z
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 418XZ
UT WOS:000264184700010
PM 19384581
ER
PT J
AU Fagan, P
Rigotti, NA
AF Fagan, Pebbles
Rigotti, Nancy A.
TI Light and intermittent smoking: The road less traveled
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Editorial Material
C1 [Fagan, Pebbles] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA.
RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4042,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA.
EM faganp@mail.nih.gov
NR 14
TC 32
Z9 32
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 FEB
PY 2009
VL 11
IS 2
BP 107
EP 110
DI 10.1093/ntr/ntn015
PG 4
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 421ZA
UT WOS:000264395600001
PM 19264864
ER
PT J
AU Fagan, P
Brook, JS
Rubenstone, E
Zhang, CS
Brook, DW
AF Fagan, Pebbles
Brook, Judith S.
Rubenstone, Elizabeth
Zhang, Chenshu
Brook, David W.
TI Longitudinal precursors of young adult light smoking among African
Americans and Puerto Ricans
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID CIGARETTE-SMOKING; SUBSTANCE USE; RACIAL-DISCRIMINATION; DEPRESSIVE
SYMPTOMS; ADOLESCENT SMOKING; SCHOOL-STUDENTS; PEER INFLUENCES; RISK
BEHAVIORS; SMOKERS; HEALTH
AB Studies have consistently documented the importance of examining light smoking among African American and Latino adolescent and adult smokers. Little is known, however, about the psychosocial antecedents of adolescent and young adult light smoking in these racial/ethnic minority groups.
This study examined the longitudinal interrelationships and pathways leading to light smoking among African Americans (n = 288) and Puerto Ricans (n = 262). Specifically, we assessed parental factors, perceived discrimination, peer smoking, personality factors, and light smoking in late adolescence as precursors to light smoking among African American and Puerto Rican young adults.
The results of structural equation modeling showed that a history of greater parental smoking, less parental educational attainment, and more perceived discrimination were each mediated by peer smoking and the youth's maladaptive personality and behavior in late adolescence. The youth's maladaptive personality and behavioral characteristics and light smoking in late adolescence, in turn, predicted light smoking in young adulthood. There were no significant racial/ethnic or gender differences in the pathways to light smoking.
Findings highlight the longitudinal pathways to light smoking among African Americans and Puerto Ricans. The results suggest that effective prevention and cessation programs must address peer and parental social influences, perceived discrimination, and especially, emotional and behavioral problems in late adolescence to reduce light smoking among late adolescents and young adults in these racial/ethnic groups.
C1 [Brook, Judith S.; Rubenstone, Elizabeth; Zhang, Chenshu; Brook, David W.] NYU, Dept Psychiat, Sch Med, New York, NY 10016 USA.
[Fagan, Pebbles] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Brook, JS (reprint author), NYU, Dept Psychiat, Sch Med, 215 Lexington Ave,15th Floor, New York, NY 10016 USA.
EM judith.brook@nyumc.org
OI Zhang, Chenshu/0000-0002-3233-3905
FU National Cancer Institute [CA 084063]; National Institute on Drug Abuse
of the National Institutes of Health [DA 00244, DA 05702]
FX National Cancer Institute (CA 084063); National Institute on Drug Abuse
of the National Institutes of Health (DA 00244 and Research Scientist
Award DA 05702) to JSB.
NR 59
TC 14
Z9 14
U1 3
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 FEB
PY 2009
VL 11
IS 2
BP 139
EP 147
DI 10.1093/ntr/ntp009
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 421ZA
UT WOS:000264395600006
PM 19251769
ER
PT J
AU Reitzel, LR
Costello, TJ
Mazas, CA
Vidrine, JI
Businelle, MS
Kendzor, DE
Li, YS
Cofta-Woerpel, L
Wetter, DW
AF Reitzel, Lorraine R.
Costello, Tracy J.
Mazas, Carlos A.
Vidrine, Jennifer I.
Businelle, Michael S.
Kendzor, Darla E.
Li, Yisheng
Cofta-Woerpel, Ludmila
Wetter, David W.
TI Low-level smoking among Spanish-speaking Latino smokers: Relationships
with demographics, tobacco dependence, withdrawal, and cessation
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID CHIPPERS
AB Although recent research indicates that many Latino smokers are nondaily smokers or daily smokers who smoke at a low level (<= 5 cigarettes/day), almost no research has investigated the characteristics of low-level smokers because such individuals are typically excluded from clinical trial research.
The present study examined the associations of daily smoking level and demographics, tobacco dependence, withdrawal, and abstinence during a specific quit attempt among 280 Spanish-speaking Latino smokers (54% male) who participated in a clinical trial of a telephone counseling intervention. Daily smokers were classified as low-level (1-5 cigarettes/day; n = 81), light (6-10 cigarettes/day; n = 99), or moderate/heavy smokers (>= 11 cigarettes/day; n = 100). Data were collected prior to the quit attempt and at 5 and 12 weeks postquit.
Results yielded three key findings. First, smoking level was positively associated with the total score and 12 of 13 subscale scores on a comprehensive, multidimensional measure of tobacco dependence. Low-level smokers consistently reported the least dependence, and moderate/heavy smokers reported the most dependence on tobacco. Second, low-level smokers reported the least craving in pre- to postcessation longitudinal analyses. Third, despite significant differences on dependence and craving, low-level smoking was not associated with abstinence. Smoking level was not associated with demographic variables.
This is a preliminary step in understanding factors influencing tobacco dependence and smoking cessation among low-level Spanish-speaking Latino smokers, a subgroup with high prevalence in the Latino population.
C1 [Reitzel, Lorraine R.; Costello, Tracy J.; Mazas, Carlos A.; Vidrine, Jennifer I.; Businelle, Michael S.; Kendzor, Darla E.; Wetter, David W.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Houston, TX 77230 USA.
[Li, Yisheng] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77230 USA.
[Cofta-Woerpel, Ludmila] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77230 USA.
[Cofta-Woerpel, Ludmila] NCI, Canc Informat Serv, Houston, TX USA.
RP Reitzel, LR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440,POB 301402, Houston, TX 77230 USA.
EM lrreitzel@mdanderson.org
RI Reitzel, Lorraine/A-4843-2014;
OI Reitzel, Lorraine/0000-0002-7165-5720; Costello,
Tracy/0000-0001-6138-2450; Kendzor, Darla/0000-0002-7947-7981; Wetter,
David/0000-0002-6366-0108; Kendzor, Darla/0000-0002-7273-1916;
Businelle, Michael/0000-0002-9038-2238; LI, Yisheng/0000-0001-9847-8544
FU National Cancer Institute [R01 CA94826, R01 CA89350, R25 CA57730];
Centers for Disease Control and Prevention [K01DP001120, K01DP000086]
FX Minority Health Research and Education Program of the Texas Higher
Education Coordinating Board; National Cancer Institute (R01 CA94826,
R01 CA89350, R25 CA57730); and Centers for Disease Control and
Prevention (K01DP001120, K01DP000086).
NR 23
TC 39
Z9 39
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD FEB
PY 2009
VL 11
IS 2
BP 178
EP 184
DI 10.1093/ntr/ntn021
PG 7
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 421ZA
UT WOS:000264395600011
PM 19246627
ER
PT J
AU Rutten, LJF
Augustson, EM
Doran, KA
Moser, RP
Hesse, BW
AF Rutten, Lila J. Finney
Augustson, Erik M.
Doran, Kelly A.
Moser, Richard P.
Hesse, Bradford W.
TI Health information seeking and media exposure among smokers: A
comparison of light and intermittent tobacco users with heavy users
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKING-CESSATION; CONTROLLED-TRIAL; INTERVENTION; INTERNET; PROGRAM
AB Introduction: We examined population-based data to assess potential differences between light and intermittent smokers as compared with moderate to heavy tobacco users in health information-seeking behavior and attitudes and media exposure.
Methods: Data from the 2003 and 2005 Health Information National Trends Surveys were combined to examine the information-seeking characteristics of light daily smokers (n = 594), intermittent smokers (n = 532), and moderate to heavy daily smokers (n = 1,131).
Results: Compared with moderate to heavy daily smokers, intermittent smokers reported less exposure to television, greater trust in doctors as a source of health information, and greater intention to quit smoking. No differences in information-seeking experiences and preferences were observed between light daily smokers and moderate to heavy daily smokers. Intermittent smokers were distinct from moderate to heavy smokers in their information-seeking experiences and preferences.
Discussion: The insight into the media use and information preferences of different smoking populations lays the groundwork for conducting further research to examine the information needs and preferences of smoking groups and to more effectively develop and deliver smoking cessation interventions.
C1 [Rutten, Lila J. Finney] HealthPartners Res Fdn, Bloomington, MN 55425 USA.
[Augustson, Erik M.; Moser, Richard P.; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Commun & Informat Res Branch,NIH, Bethesda, MD 20892 USA.
[Doran, Kelly A.] Div Canc Control & Populat Sci, Silver Spring, MD USA.
[Doran, Kelly A.] DB Consulting Grp Inc, Silver Spring, MD USA.
RP Rutten, LJF (reprint author), HealthPartners Res Fdn, 8170 33rd Ave S, Bloomington, MN 55425 USA.
EM lila.j.rutten@healthpartners.com
OI Hesse, Bradford/0000-0003-1142-1161
NR 30
TC 25
Z9 25
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD FEB
PY 2009
VL 11
IS 2
BP 190
EP 196
DI 10.1093/ntr/ntn019
PG 7
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 421ZA
UT WOS:000264395600013
PM 19264865
ER
PT J
AU Apinunmahakul, A
Barham, V
Devlin, RA
AF Apinunmahakul, Amornrat
Barham, Vicky
Devlin, Rose Anne
TI Charitable Giving, Volunteering, and the Paid Labor Market
SO NONPROFIT AND VOLUNTARY SECTOR QUARTERLY
LA English
DT Article
DE charitable giving; volunteering; labor market; altruism; philanthropy
ID PUBLIC-GOODS; CROWD; MONEY; TIME; TAX
AB Among the few articles that jointly determine an individual's gifts of time and money, there exists disagreement as to whether these gifts are complements or substitutes. The authors try to shed some light on this debate by expanding the analysis of private contributions to take account of whether or not the individual is working in the paid labor market. The analysis indicates that gifts of time and money are largely complementary to each other, especially for employed individuals. The donations of employed males also appear to be crowded out by government expenditures. The fact that employment status as well as gender affect how individuals respond to fiscal stimulus may have important policy implications.
C1 [Apinunmahakul, Amornrat] NIDA, Sch Dev Econ, Bangkok, Thailand.
[Barham, Vicky; Devlin, Rose Anne] Univ Ottawa, Ottawa, ON K1N 6N5, Canada.
RP Apinunmahakul, A (reprint author), NIDA, Sch Dev Econ, Bangkok, Thailand.
NR 22
TC 10
Z9 10
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0899-7640
J9 NONPROF VOLUNT SEC Q
JI Nonprofit Volunt. Sect. Q.
PD FEB
PY 2009
VL 38
IS 1
BP 77
EP 94
DI 10.1177/0899764008315845
PG 18
WC Social Issues
SC Social Issues
GA 389NP
UT WOS:000262100400004
ER
PT J
AU Altschul, SF
Gertz, EM
Agarwala, R
Schaffer, AA
Yu, YK
AF Altschul, Stephen F.
Gertz, E. Michael
Agarwala, Richa
Schaffer, Alejandro A.
Yu, Yi-Kuo
TI PSI-BLAST pseudocounts and the minimum description length principle
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ACID SUBSTITUTION MATRICES; SEQUENCE WEIGHTS; PROTEIN-SEQUENCE;
DATABASE; ALIGNMENT; INFORMATION; HOMOLOGY; SEARCHES; BLOCKS
AB Position specific score matrices (PSSMs) are derived from multiple sequence alignments to aid in the recognition of distant protein sequence relationships. The PSI-BLAST protein database search program derives the column scores of its PSSMs with the aid of pseudocounts, added to the observed amino acid counts in a multiple alignment column. In the absence of theory, the number of pseudocounts used has been a completely empirical parameter. This article argues that the minimum description length principle can motivate the choice of this parameter. Specifically, for realistic alignments, the principle supports the practice of using a number of pseudocounts essentially independent of alignment size. However, it also implies that more highly conserved columns should use fewer pseudocounts, increasing the inter-column contrast of the implied PSSMs. A new method for calculating pseudocounts that significantly improves PSI-BLAST's retrieval accuracy is now employed by default.
C1 [Altschul, Stephen F.; Gertz, E. Michael; Agarwala, Richa; Schaffer, Alejandro A.; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Altschul, SF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM altschul@ncbi.nlm.nih.gov
RI Schaffer, Alejandro/F-2902-2012;
OI Gertz, E. Michael/0000-0001-8390-4387
FU Intramural NIH HHS
NR 35
TC 48
Z9 49
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2009
VL 37
IS 3
BP 815
EP 824
DI 10.1093/nar/gkn981
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 413YP
UT WOS:000263831400025
PM 19088134
ER
PT J
AU Keating, CP
Hill, MK
Hawkes, DJ
Smyth, RP
Isel, C
Le, SY
Palmenberg, AC
Marshall, JA
Marquet, R
Nabel, GJ
Mak, J
AF Keating, Cameron P.
Hill, Melissa K.
Hawkes, David J.
Smyth, Redmond P.
Isel, Catherine
Le, Shu-Yun
Palmenberg, Ann C.
Marshall, John A.
Marquet, Roland
Nabel, Gary J.
Mak, Johnson
TI The A-rich RNA sequences of HIV-1 pol are important for the synthesis of
viral cDNA
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; REV-INDEPENDENT EXPRESSION; MURINE
LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; GENOMIC RNA; CODON USAGE;
IN-VIVO; DIMER STABILITY; NONCODING RNA; DNA FLAP
AB The bias of A-rich codons in HIV-1 pol is thought to be a record of hypermutations in viral genomes that lack biological functions. Bioinformatic analysis predicted that A-rich sequences are generally associated with minimal local RNA structures. Using codon modifications to reduce the amount of A-rich sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences in pol to analyze the functional significance of these A-rich 'structurally poor' RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1 sequences led to a suppression of virus infectivity by 5-100-fold, and this defect does not correlate with, viral entry, viral protein expression levels, viral protein profiles or virion packaging of genomic RNA. Codon modification of HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome, which was associated with a reduction of viral cDNA synthesis both during HIV-1 infection and in a cell free reverse transcription assay. Our data provided direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on A-rich RNA sequences to support the synthesis of viral cDNA during reverse transcription, highlighting the utility of using structurally poor' RNA domains in regulating biological process.
C1 [Keating, Cameron P.; Hill, Melissa K.; Hawkes, David J.; Smyth, Redmond P.; Mak, Johnson] Macfarlane Burnet Inst Med Res & Publ Hlth, Ctr Virol, Melbourne, Vic, Australia.
[Hawkes, David J.; Smyth, Redmond P.; Mak, Johnson] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
[Hill, Melissa K.; Mak, Johnson] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia.
[Isel, Catherine; Marquet, Roland] Univ Strasbourg, CNRS, IBMC, Architecture & Reactivite ARN, Strasbourg, France.
[Le, Shu-Yun] NCI, Ctr Canc Res Nanobiol Program, CCR, Frederick, MD 21701 USA.
[Palmenberg, Ann C.] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA.
[Marshall, John A.] VIDRL, Melbourne, Vic, Australia.
[Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mak, J (reprint author), Macfarlane Burnet Inst Med Res & Publ Hlth, Ctr Virol, Melbourne, Vic, Australia.
EM mak@burnet.edu.au
RI mak, johnson/H-4605-2014; Isel, Catherine/B-9406-2015;
OI mak, johnson/0000-0002-5229-5707; Isel, Catherine/0000-0001-7258-869X;
Hawkes, David/0000-0002-3882-801X; Smyth, Redmond/0000-0002-1580-0671;
Marquet, Roland/0000-0002-4209-3976
FU Intramural NIH HHS
NR 72
TC 15
Z9 15
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2009
VL 37
IS 3
BP 945
EP 956
DI 10.1093/nar/gkn1015
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 413YP
UT WOS:000263831400037
PM 19106143
ER
PT J
AU Bogardus, C
AF Bogardus, Clifton
TI Missing Heritability and GWAS Utility
SO OBESITY
LA English
DT Editorial Material
ID BODY-MASS INDEX; HUMAN OBESITY; COMMON; POPULATION; CHILDHOOD; VARIANTS;
MC4R; RISK
C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
RP Bogardus, C (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
EM clifton_bogardus@nih.gov
FU Intramural NIH HHS [Z01 DK069015-25]
NR 14
TC 44
Z9 48
U1 1
U2 9
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 FEB
PY 2009
VL 17
IS 2
BP 209
EP 210
DI 10.1038/oby.2008.613
PG 2
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 400VJ
UT WOS:000262897200001
PM 19169219
ER
PT J
AU Caritis, SN
Rouse, DJ
Peaceman, AM
Sciscione, A
Momirova, V
Spong, CY
Iams, JD
Wapner, RJ
Varner, M
Carpenter, M
Lo, J
Thorp, J
Mercer, BM
Sorokin, Y
Harper, M
Ramin, S
Anderson, G
AF Caritis, Steve N.
Rouse, Dwight J.
Peaceman, Alan M.
Sciscione, Anthony
Momirova, Valerija
Spong, Catherine Y.
Iams, Jay D.
Wapner, Ronald J.
Varner, Michael
Carpenter, Marshall
Lo, Julie
Thorp, John
Mercer, Brian M.
Sorokin, Yoram
Harper, Margaret
Ramin, Susan
Anderson, Garland
CA Kennedy Shriver Natl Inst Child Hu
Maternal-Fetal Med Units Network M
TI Prevention of Preterm Birth in Triplets Using 17
Alpha-Hydroxyprogesterone Caproate A Randomized Controlled Trial
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; CLINICAL-TRIALS; RAT MYOMETRIUM;
DELIVERY; PROGESTERONE; EXPRESSION; PREGNANCY; LABOR
AB OBJECTIVE: To assess whether 17 alpha-hydroxyprogesterone caproate reduces the rate of preterm birth in women carrying triplets.
METHODS: We performed this randomized, double-blinded, placebo-controlled trial in 14 centers. Healthy women with triplets were randomly assigned to weekly intramuscular injections of either 250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo, starting at 16-20 weeks and ending at delivery or 35 weeks of gestation. The primary study outcome was delivery or fetal loss before 35 weeks.
RESULTS: One hundred thirty-four women were assigned, 71 to 17 alpha-hydroxyprogesterone caproate and 63 to placebo; none were lost to follow-up. Baseline demographic data were similar in the two groups. The proportion of women experiencing the primary outcome (a composite of delivery or fetal loss before 35 0/7 weeks) was similar in the two treatment groups: 83% of pregnancies in the 17 alpha-hydroxyprogesterone caproate group and 84% in the placebo group, relative risk 1.0, 95% confidence interval 0.9-1.1. The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident regardless of the conception method or whether a gestational age cutoff for delivery was set at 32 or 28 weeks.
CONCLUSION: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with triplet gestations.
C1 Univ Pittsburgh, Dept Obstet, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Gynecol, Pittsburgh, PA USA.
Univ Alabama, Ctr Women Reprod Hlth, Birmingham, AL USA.
Northwestern Univ, Chicago, IL 60611 USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Ohio State Univ, Columbus, OH 43210 USA.
Columbia Univ, New York, NY USA.
Univ Utah, Salt Lake City, UT USA.
Brown Univ, Providence, RI USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ N Carolina, Chapel Hill, NC USA.
Case Western Reserve Univ, Cleveland, OH 44106 USA.
Wayne State Univ, Detroit, MI USA.
Wake Forest Univ, Winston Salem, NC 27109 USA.
Univ Texas Houston, Houston, TX USA.
Univ Texas Med Branch, Galveston, TX USA.
RP Caritis, SN (reprint author), 300 Halket St,Room 2229, Pittsburgh, PA 15213 USA.
EM scaritis@mail.magee.edu
RI Varner, Michael/K-9890-2013;
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973;
Peaceman, Alan/0000-0002-4515-4850
FU Etinice Kennedy Shriver National Institute of Child, Health and Human
Development [HD21410, HD2 7869, HD40512, HD2 7975, HD40485, HD34208,
HD40500, HD34776, HD40560, HD40544, HD27917, HD27860, HD40545, HD53097,
HD36801, HD34136]
FX Sopported by grants from the Etinice Kennedy Shriver National Institute
of Child, Health and Human Development, (HD21410; HD2 7869; HD40512; HD2
7975; HD40485; HD34208, HD40500; HD34776; HD40560, HD40544; HD27917;
HD27860; HD40545; HD53097; HD36801; HD34136).
NR 23
TC 63
Z9 64
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD FEB
PY 2009
VL 113
IS 2
BP 285
EP 292
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 399YK
UT WOS:000262835000006
PM 19155896
ER
PT J
AU Kuklina, EV
Meikle, SF
Jamieson, DJ
Whiteman, MK
Barfield, WD
Hillis, SD
Posner, SF
AF Kuklina, Elena V.
Meikle, Susan F.
Jamieson, Denise J.
Whiteman, Maura K.
Barfield, Wanda D.
Hillis, Susan D.
Posner, Samuel F.
TI Severe Obstetric Morbidity in the United States: 1998-2005
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID MATERNAL MORBIDITY; PREGNANCY; MORTALITY; DELIVERY; TRANSFUSION;
HEMORRHAGE; OUTCOMES; RISK
AB OBJECTIVE: To examine trends in the rates of severe obstetric complications and the potential contribution of changes in delivery mode and maternal characteristics to these trends.
METHODS: We performed a cross-sectional study of severe obstetric complications identified from the 1998-2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Logistic regression was used to examine the effect of changes in delivery mode and maternal characteristics on rates of severe obstetric complications.
RESULTS: The prevalence of delivery hospitalizations (per 1,000) complicated by at least one severe obstetric complication increased from 0.64% (n=48,645) in 1998-1999 to 0.81% (n=68,433) in 2004-2005. Rates of complications that increased significantly during the study period included renal failure by 21% (from 0.23 to 0.28), pulmonary embolism by 52% (0.12 to 0.18), adult respiratory distress syndrome by 26% (0.36 to 0.45), shock by 24% (0.15 to 0.19), blood transfusion by 92% (2.38 to 4.58), and ventilation by 21% (0.47 to 0.57). In logistic regression models, adjustment for maternal age had no effect on the increased risk for these complications in 2004-2005 relative to 1998-1999. However, after adjustment for mode of delivery, the increased risks for these complications in 2004-2005 relative to 1998-1999 were no longer significant, with the exception of pulmonary embolism (odds ratio 1.30) and blood transfusion (odds ratio 1.72). Further adjustment for payer, multiple births, and select comorbidities had little effect.
CONCLUSION: Rates of severe obstetric complications increased from 1998-1999 to 2004-2005. For many of these complications, these increases were associated with the increasing rate of cesarean delivery.
C1 Quantell Inc, Taneytown, MD USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA USA.
RP Meikle, SF (reprint author), NICHD, CRHB, NIH, 6100 Execut Blvd,Suite 8B13C, Bethesda, MD 20892 USA.
EM meikles@mail.nih.gov
OI Posner, Samuel/0000-0003-1574-585X
FU Intramural NIH HHS [Z99 HD999999]
NR 20
TC 102
Z9 105
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD FEB
PY 2009
VL 113
IS 2
BP 293
EP 299
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 399YK
UT WOS:000262835000007
PM 19155897
ER
PT J
AU Huff, J
Infante, P
AF Huff, J.
Infante, P.
TI Identifying cancer sites for human carcinogens in the IARC monographs
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Letter
ID FORMALDEHYDE
C1 [Huff, J.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Infante, P.] George Washington Univ, Washington, DC USA.
RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM huff1@niehs.nih.gov
RI Richardson, Sylvia/G-4691-2015
OI Richardson, Sylvia/0000-0003-1998-492X
NR 7
TC 2
Z9 2
U1 1
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD FEB
PY 2009
VL 66
IS 2
BP 140
EP 140
DI 10.1136/oem.2008.042036
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 396HG
UT WOS:000262582200013
PM 19151229
ER
PT J
AU Ren, L
Hong, SH
Cassavaugh, J
Osborne, T
Chou, AJ
Kim, SY
Gorlick, R
Hewitt, SM
Khanna, C
AF Ren, L.
Hong, S. H.
Cassavaugh, J.
Osborne, T.
Chou, A. J.
Kim, S. Y.
Gorlick, R.
Hewitt, S. M.
Khanna, C.
TI The actin-cytoskeleton linker protein ezrin is regulated during
osteosarcoma metastasis by PKC
SO ONCOGENE
LA English
DT Article
DE ezrin; ERM; PKC; tumor metastasis
ID EZRIN/RADIXIN/MOESIN ERM PROTEINS; KINASE-C; PLASMA-MEMBRANE;
EPITHELIAL-CELLS; CARCINOMA-CELLS; T-LYMPHOCYTES; CRUCIAL ROLE;
PHOSPHORYLATION; EXPRESSION; MOESIN
AB Ezrin is a member of the ERM (ezrin, radixin, moesin) protein family and links F-actin to the cell membrane following phosphorylation. Ezrin has been associated with tumor progression and metastasis in several cancers including the pediatric solid tumors, osteosarcoma and rhabdomyosarcoma. In this study, we were surprised to find that ezrin was not constitutively phosphorylated but rather was dynamically regulated during metastatic progression in osteosarcoma. Metastatic osteosarcoma cells expressed phosphorylated ERM early after their arrival in the lung, and then late in progression, only at the invasive front of larger metastatic lesions. To pursue mechanisms for this regulation, we found that inhibitors of PKC (protein kinase C) blocked phosphorylation of ezrin, and that ezrin coimmunoprecipitated in cells with PKC alpha, PKC iota and PKC gamma. Furthermore, phosphorylated forms of ezrin and PKC had identical expression patterns at the invasive front of pulmonary metastatic lesions in murine and human patient samples. Finally, we showed that the promigratory effects of PKC were linked to ezrin phosphorylation. These data are the first to suggest a dynamic regulation of ezrin phosphorylation during metastasis and to connect the PKC family members with this regulation.
C1 [Khanna, C.] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chou, A. J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Gorlick, R.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Dept Pediat, Bronx, NY USA.
[Hewitt, S. M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res, 37 Convent Dr,Rm 2144, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov
OI Chou, Alexander/0000-0002-7926-3326; Hewitt, Stephen/0000-0001-8283-1788
NR 51
TC 66
Z9 75
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD FEB
PY 2009
VL 28
IS 6
BP 792
EP 802
DI 10.1038/onc.2008.437
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 406UI
UT WOS:000263320000002
PM 19060919
ER
PT J
AU Guo, C
Gasparian, AV
Zhuang, Z
Bosykh, DA
Komar, AA
Gudkov, AV
Gurova, KV
AF Guo, C.
Gasparian, A. V.
Zhuang, Z.
Bosykh, D. A.
Komar, A. A.
Gudkov, A. V.
Gurova, K. V.
TI 9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR,
NF-kappa B and p53 pathways
SO ONCOGENE
LA English
DT Article
DE proteomics; quinacrine; cell death; PI3 kinase-gamma; PTEN
ID RHEUMATOID-ARTHRITIS; MESSENGER-RNAS; CELLS; INFLAMMATION; PI3K-GAMMA;
KINASE; TRANSLATION; INHIBITION; ACTIVATION; MECHANISM
AB Acquisition of a transformed phenotype involves deregulation of several signal transduction pathways contributing to unconstrained cell growth. Understanding the interplay of different cancer-related signaling pathways is important for development of efficacious multitargeted anticancer drugs. The small molecule 9-aminoacridine (9AA) and its derivative, the antimalaria drug quinacrine, have selective toxicity for tumor cells and can simultaneously suppress nuclear factor-kappa B (NF-kappa B) and activate p53 signaling. To investigate the mechanism underlying these drug activities, we used a combination of two-dimensional protein separation by gel electrophoresis and mass spectrometry to identify proteins whose expression is altered in tumor cells by 9AA treatment. We found that 9AA treatment results in selective downregulation of a specific catalytic subunit of the phosphoinositide 3-kinase (PI3K) family, p110 gamma. Further exploration of this observation demonstrated that the mechanism of action of 9AA involves inhibition of the prosurvival AKT/ mammalian target of rapamycin (mTOR) pathway that lies downstream of PI3K. p110 gamma translation appears to be regulated by mTOR and feeds back to further modulate mTOR and AKT, there by impacting the p53 and NF-kappa B pathways as well. These results reveal functional interplay among the PI3K/AKT/mTOR, p53 and NF-kappa B pathways that are frequently deregulated in cancer and suggest that their simultaneous targeting by a single small molecule such as 9AA could result in efficacious and selective killing of transformed cells.
C1 [Gudkov, A. V.; Gurova, K. V.] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA.
[Guo, C.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
[Guo, C.] Lerner Res Inst, Dept Mol Genet, Cleveland, OH USA.
[Gasparian, A. V.; Bosykh, D. A.; Gudkov, A. V.; Gurova, K. V.] Cleveland Biolabs Inc, Buffalo, NY USA.
[Zhuang, Z.] Natl Inst Hlth, Bethesda, MD USA.
[Komar, A. A.] Cleveland State Univ, Dept Biol, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
RP Gudkov, AV (reprint author), Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC L3-301,Elm & Carlton St, Buffalo, NY 14263 USA.
EM andrei.gudkov@roswellpark.org; katerina.gurova@roswellpark.org
NR 29
TC 64
Z9 68
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD FEB
PY 2009
VL 28
IS 8
BP 1151
EP 1161
DI 10.1038/onc.2008.460
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 412KE
UT WOS:000263722900010
PM 19137016
ER
PT J
AU Shi, Z
Parmar, S
Peng, XX
Shen, T
Robey, RW
Bates, SE
Fu, LW
Shao, YN
Chen, YM
Zang, FY
Chen, ZS
AF Shi, Zhi
Parmar, Smitaben
Peng, Xing-Xiang
Shen, Tong
Robey, Robert W.
Bates, Susan E.
Fu, Li-Wu
Shao, Yining
Chen, Yang-Min
Zang, Feiyang
Chen, Zhe-Sheng
TI The epidermal growth factor tyrosine kinase inhibitor AG1478 and
erlotinib reverse ABCG2-mediated drug resistance
SO ONCOLOGY REPORTS
LA English
DT Article
DE multidrug resistance; ABCG2; AG1478; erlotinib
ID MULTIDRUG-RESISTANCE; FACTOR RECEPTOR; CANCER-CELLS; P-GLYCOPROTEIN;
IMATINIB MESYLATE; IN-VITRO; HALF-TRANSPORTER; FUMITREMORGIN-C; ABCG2
BCRP; PROTEIN
AB ABCG2 is an important member of ATP-binding cassette (ABC) transporter shown to confer drug resistance in cancer cells. Recent studies show that an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib, is able to modulate the function of ABCG2 and reverse ABCG2-mediated multidrug resistance (MDR) in cancer cells. Additionally, ABCG2 expression has been shown to impact treatment efficacy and development of side-effects in patients receiving gefitinib. However, it is unclear whether other EGFR TKIs interact with ABCG2 in a similar manner. In the present study, we investigated the interaction of two other EGFR TKIs, AG1478 and erlotinib, with ABCG2. Our data show that AG1478 and erlotinib potently sensitized drug-resistant cells overexpressing either wild-type or mutated ABCG2 to the ABCG2 substrate anti-cancer drugs flavopiridol and mitoxantrone. Neither AG1478 nor erlotinib sensitized ABCG2-overexpressing cells to drugs that are not substrates of ABCG2 nor did they impact drug sensitivity of parental cells. Furthermore, AG1478 and erlotinib were able to significantly enhance the intracellular accumulation of mitoxantrone in cells expressing either wildtype or mutated ABCG2. Additionally, they did not alter the protein expression of ABCG2 in the ABCG2-overexpressing cells. Taken together, we conclude that AG1478 and erlotinib potently reverse ABCG2-mediated MDR through directly inhibiting the drug efflux function of ABCG2 in the ABCG2-overexpressing cells. These results will be useful in the development of novel and more effective EGFR TKIs as well as the development of combinational chemotherapeutic strategies.
C1 [Shi, Zhi; Parmar, Smitaben; Peng, Xing-Xiang; Shen, Tong; Shao, Yining; Chen, Yang-Min; Zang, Feiyang; Chen, Zhe-Sheng] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA.
[Shi, Zhi; Fu, Li-Wu] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
[Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA.
EM chenz@stjohns.edu
RI Shen, Tong/C-8853-2012
FU St. John's University Tenure Track Faculty Start-Up [C0531]; St. John's
University [579-1110]
FX We thank OSI Pharmaceuticals (Melville, NY) for providing erlotinib.
This work was supported by funds from St. John's University Tenure Track
Faculty Start-Up Funding (No. C0531, Z.S. Chen) and Seed Grant of St.
John's University (No. 579-1110, Z.S. Chen). Z. Shi is a recipient of
Kaisi fellowship for overseas study at St. John's University from Sun
Yat-Sen University. Yining Shao, Yang-Min Chen and Feiyang Zang are the
summer research students from high schools.
NR 37
TC 34
Z9 37
U1 0
U2 10
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD FEB
PY 2009
VL 21
IS 2
BP 483
EP 489
DI 10.3892/or_00000248
PG 7
WC Oncology
SC Oncology
GA 397RH
UT WOS:000262679300031
PM 19148526
ER
PT J
AU Chew, EY
Sperduto, RD
Milton, RC
Clemons, TE
Gensler, GR
Bressler, SB
Klein, R
Klein, BEK
Ferris, FL
AF Chew, Emily Y.
Sperduto, Robert. D.
Milton, Roy C.
Clemons, Traci E.
Gensler, Gary R.
Bressler, Susan B.
Klein, Ronald
Klein, Barbara E. K.
Ferris, Frederick L., III
TI Risk of Advanced Age-Related Macular Degeneration after Cataract Surgery
in the Age-Related Eye Disease Study AREDS Report 25
SO OPHTHALMOLOGY
LA English
DT Article
ID BLUE MOUNTAINS EYE; VISUAL IMPAIRMENT; INTRAOCULAR-LENS; SEVERITY SCALE;
BEAVER DAM; MACULOPATHY; ASSOCIATION; EXTRACTION; IMPLANTATION;
PREVALENCE
AB Purpose: To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery.
Design: Cohort study.
Participants: Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS).
Methods: Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately.
Main Outcome Measures: Neovascular AMD, GA, and central GA (CGA; involving the center of the macula).
Results: The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA.
Conclusions. The AREDS results show-ad no clear effect of cataract surgery on the risk of progression to advanced AMD.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:297-303 (C) 2009 by the American Academy of Ophthalmology.
C1 [Chew, Emily Y.; Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA.
[Bressler, Susan B.] Johns Hopkins Wilmer Eye Inst, Baltimore, MD USA.
[Sperduto, Robert. D.; Milton, Roy C.; Clemons, Traci E.; Gensler, Gary R.] EMMES Corp, Rockville, MD USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
RP Chew, EY (reprint author), NEI, Bethesda, MD 20892 USA.
OI Klein, Ronald/0000-0002-4428-6237
FU National Eye Institute; National Institutes of Health; Department of
Health and Human Services, Bethesda, Maryland
FX Supported by contracts from the National Eye Institute, National
Institutes of Health, Department of Health and Human Services, Bethesda,
Maryland.
NR 22
TC 66
Z9 69
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2009
VL 116
IS 2
BP 297
EP 303
DI 10.1016/j.ophtha.2008.09.019
PG 7
WC Ophthalmology
SC Ophthalmology
GA 403QW
UT WOS:000263098100020
PM 19091420
ER
PT J
AU Imrich, R
Eldadah, BA
Bentho, O
Pechnik, S
Sharabi, Y
Holmes, C
Grossman, E
Goldstein, DS
AF Imrich, Richard
Eldadah, Basil A.
Bentho, Oladi
Pechnik, Sandra
Sharabi, Yehonatan
Holmes, Courtney
Grossman, Ehud
Goldstein, David S.
TI Functional effects of cardiac sympathetic denervation in neurogenic
orthostatic hypotension
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson disease; Pure autonomic failure; Sympathetic denervation;
Pre-ejection period
ID SYSTOLIC-TIME INTERVALS; PARKINSONS-DISEASE; DOPAMINE CONTAMINATION;
TYRAMINE; VASODILATION; SENSITIVITY; ACTIVATION; PRESSURE; INDEXES
AB Background: Diseases characterized by neurogenic orthostatic hypotension (NOH), such as Parkinson disease (PD) and pure autonomic failure (PAF), are associated with cardiac sympathetic denervation, as reflected by low myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity. We Studied the impact of such denervation on cardiac chronotropic and inotropic function.
Methods: Cardiac inotropic function was assessed by the pre-ejection period index and the systolic time ratio index in response to the directly acting beta-adrenoceptor agonist, isoproterenol, and to the indirectly acting sympathomimetic amine, tyramine, in patients with PD+NOH or PAF (PD + NOH/PAF group, N = 13). We compared the results to those in patients with multiple system atrophy, which Usually entails NOH with normal cardiac sympathetic innervation (MSA, N = 15), and in normal control subjects (N = 5).
Results: The innervated and denervated groups did not differ in baseline mean pre-ejection period index or systolic time ratio index. Tyramine increased cardiac contractility in the MSA patients and controls but not in the PD + NOR/PAF group. For similar heart rate responses, the PD + NOH/PAF group required less isoproterenol (p < 0.01) and had lower plasma isoproterenol levels (p < 0.01) than did the MSA group.
Conclusions: Among patients with NOH those with cardiac sympathetic denervation have an impaired inotropic response to tyramine and exaggerated responses to isoproterenol. This pattern suggests that cardiac denervation is associated with decreased ability to release endogenous norepinephrine from sympathetic nerves and with supersensitivity of cardiac beta-adrenoreceptors, Published by Elsevier Ltd.
C1 [Imrich, Richard; Eldadah, Basil A.; Bentho, Oladi; Pechnik, Sandra; Holmes, Courtney; Goldstein, David S.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
[Sharabi, Yehonatan; Grossman, Ehud] Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel.
[Sharabi, Yehonatan; Grossman, Ehud] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.
RP Imrich, R (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Vlarska 3, SK-83306 Bratislava, Slovakia.
EM richard.imrich@savba.sk
OI Grossman, Ehud/0000-0001-8353-0661
FU NIH
FX The research reported here was supported by the intramural research
program of the NIH.
NR 26
TC 18
Z9 19
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD FEB
PY 2009
VL 15
IS 2
BP 122
EP 127
DI 10.1016/j.parkreldis.2008.04.002
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 407ZA
UT WOS:000263401600008
PM 18514012
ER
PT J
AU King, JR
Acosta, EP
Yogev, R
Wiznia, A
Kraimer, J
Graham, B
Carey, V
Britto, P
Jean-Philippe, P
Moye, J
Watson, D
AF King, Jennifer R.
Acosta, Edward P.
Yogev, Ram
Wiznia, Andrew
Kraimer, Joyce
Graham, Bobbie
Carey, Vincent
Britto, Paula
Jean-Philippe, Patrick
Moye, John
Watson, Douglas
TI STEADY-STATE PHARMACOKINETICS OF LOPINAVIR/RITONAVIR IN COMBINATION WITH
EFAVIRENZ IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PEDIATRIC PATIENTS
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE HIV; pharmacokinetics; lopinavir/ritonavir; efavirenz
ID REVERSE-TRANSCRIPTASE INHIBITORS; HIV-1-INFECTED CHILDREN; GUIDELINES
AB The pharmacokinetics of lopinavir/ritonavir (LPV/RTV) 300 mg/m(2) twice daily and efavirenz (EFV) 350 mg/m(2) once daily were evaluated in HIV-infected children. The minimum concentrations for LPV contained values above the target range, and the estimated minimum concentrations for EFV contained values below the range. Our data support the current LPV/RTV dose, but EFV 350 mg/m(2) may not be sufficient.
C1 [King, Jennifer R.] Univ Alabama, Div Clin Pharmacol, Birmingham, AL 35294 USA.
[Yogev, Ram] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Chicago, IL 60614 USA.
[Wiznia, Andrew] Jacobi Med Ctr, Brooklyn, NY USA.
[Kraimer, Joyce] Social & Sci Syst Inc, Silver Spring, MD USA.
[Graham, Bobbie] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA.
[Carey, Vincent; Britto, Paula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn, Therapeut Res Program, DAIDS,NIH, Bethesda, MD 20892 USA.
[Moye, John] NICHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Watson, Douglas] Univ Maryland, Baltimore, MD 21201 USA.
RP King, JR (reprint author), Univ Alabama, Div Clin Pharmacol, 1530 3rd Ave S,VH 101A, Birmingham, AL 35294 USA.
EM jennifer.king@ccc.uab.edu
OI moye, john/0000-0001-9976-8586
FU National Institute of Allergy and Infectious Diseases [U01AI068632]
FX Supported by grant number U01AI068632 from the National Institute of
Allergy and Infectious Diseases.
NR 11
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD FEB
PY 2009
VL 28
IS 2
BP 159
EP 161
DI 10.1097/INF.0b013e3181861d8b
PG 3
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 401OX
UT WOS:000262952100021
PM 19106779
ER
PT J
AU Turkbey, B
Ocak, I
Daryanani, K
Font-Montgomery, E
Lukose, L
Bryant, J
Tuchman, M
Mohan, P
Heller, T
Gahl, WA
Choyke, PL
Gunay-Aygun, M
AF Turkbey, Baris
Ocak, Iclal
Daryanani, Kailash
Font-Montgomery, Esperanza
Lukose, Linda
Bryant, Joy
Tuchman, Maya
Mohan, Parvathi
Heller, Theo
Gahl, William A.
Choyke, Peter L.
Gunay-Aygun, Meral
TI Autosomal recessive polycystic kidney disease and congenital hepatic
fibrosis (ARPKD/CHF)
SO PEDIATRIC RADIOLOGY
LA English
DT Review
DE Autosomal recessive polycystic kidney disease; Congenital hepatic
fibrosis; US; MR cholangiography; Children
ID GENE
AB ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform dilatation of the renal collecting ducts leading to enlarged spongiform kidneys and ductal plate malformation of the liver resulting in congenital hepatic fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the kidney and liver. Imaging plays an important role in the diagnosis and follow-up of ARPKD/CHF. Combined use of conventional and high-resolution US with MR cholangiography in ARPKD/CHF patients allows detailed definition of the extent of kidney and hepatobiliary manifestations without requiring ionizing radiation and contrast agents.
C1 [Font-Montgomery, Esperanza; Lukose, Linda; Bryant, Joy; Tuchman, Maya; Gahl, William A.; Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Ocak, Iclal; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Daryanani, Kailash] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA.
[Mohan, Parvathi] George Washington Univ, Dept Pediat Gastroenterol, Washington, DC USA.
[Heller, Theo] NIDDK, NIH, Bethesda, MD USA.
[Gunay-Aygun, Meral] NIH, Intramural Program, Off Rare Dis, Off Directors, Bethesda, MD 20892 USA.
RP Gunay-Aygun, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM mgaygun@mail.nih.gov
FU National Human Genome Research Institute; National Cancer Institute;
National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health Clinical Center
FX We thank the ARPKD/CHF Alliance and all patients and their families who
generously participated in this investigation. Supported by the
intramural research programs of the National Human Genome Research
Institute, National Cancer Institute, National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Institutes of Health
Clinical Center.
NR 12
TC 36
Z9 43
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD FEB
PY 2009
VL 39
IS 2
BP 100
EP 111
DI 10.1007/s00247-008-1064-x
PG 12
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 387NK
UT WOS:000261958700002
PM 19089418
ER
PT J
AU Kleinerman, RA
AF Kleinerman, Ruth A.
TI Radiation-sensitive genetically susceptible pediatric sub-populations
SO PEDIATRIC RADIOLOGY
LA English
DT Article
DE Second cancers; Radiotherapy; Retinoblastoma; Neurofibromatosis type 1;
Li-Fraumeni syndrome; Nevoid basal cell carcinoma syndrome
ID NERVE SHEATH TUMORS; SOFT-TISSUE SARCOMAS; LI-FRAUMENI-SYNDROME; 2ND
PRIMARY TUMORS; HEREDITARY RETINOBLASTOMA; THERAPEUTIC RADIATION;
SUBSTANTIAL RISKS; CHILDHOOD-CANCER; UNITED-STATES; FOLLOW-UP
AB Major advances in pediatric cancer treatment have resulted in Substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to Ionizing radiation.
C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7044, Rockville, MD 20852 USA.
EM kleinerr@mail.nih.gov
OI Kleinerman, Ruth/0000-0001-7415-2478
FU Intramural NIH HHS [Z01 CP010131-12]
NR 38
TC 40
Z9 42
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD FEB
PY 2009
VL 39
BP S27
EP S31
DI 10.1007/s00247-008-1015-6
PG 5
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 452TF
UT WOS:000266563400003
PM 19083227
ER
PT J
AU Linet, MS
Kim, KP
Rajaraman, P
AF Linet, Martha S.
Kim, Kwang pyo
Rajaraman, Preetha
TI Children's exposure to diagnostic medical radiation and cancer risk:
epidemiologic and dosimetric considerations
SO PEDIATRIC RADIOLOGY
LA English
DT Review
DE Ionizing radiation; Pediatric neoplasms; Cancer risks; Diagnostic
radiography; CT
ID ATOMIC-BOMB SURVIVORS; X-RAY-EXPOSURE; ACUTE NONLYMPHOCYTIC LEUKEMIA;
CENTRAL-NERVOUS-SYSTEM; CHILDHOOD-CANCER; THYROID-CANCER; BREAST-CANCER;
BRAIN-TUMORS; CARDIAC-CATHETERIZATION; INTRAUTERINE EXPOSURE
AB While the etiology of most childhood cancers is largely unknown, epiderniologic studies have consistently found an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The relation between early life diagnostic radiation exposure and occurrence of pediatric cancer risks is less clear. This review summarizes current and historical estimated doses for common diagnostic radiologic procedures as well as the epiderniologic literature on the role of maternal prenatal, children's postnatal and parental preconception diagnostic radiologic procedures on subsequent risk of childhood malignancies. Risk estimates are presented according to factors such as the year of birth of the child, trimester and medical indication for the procedure, and the number of films taken. The paper also discusses limitations of the methods employed in epidemiologic studies to assess pediatric cancer risks, the effects on clinical practice of the results reported from the epiderniologic studies, and clinical and public health policy implications of the findings. Gaps in understanding and additional research needs are identified. Important research priorities include nationwide surveys to estimate fetal and childhood radiation doses from common diagnostic procedures, and epiderniologic studies to quantify pediatric and lifetime cancer risks from prenatal and early childhood exposures to diagnostic radiography, CT, and fluoroscopically guided procedures.
C1 [Linet, Martha S.; Kim, Kwang pyo; Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA.
EM linetm@mail.nih.gov
FU National Cancer Institute; National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. The authors
thank Annelie Landgren for technical support.
NR 126
TC 108
Z9 111
U1 5
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
EI 1432-1998
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD FEB
PY 2009
VL 39
SU 1
BP S4
EP S26
DI 10.1007/s00247-008-1026-3
PG 23
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 452TF
UT WOS:000266563400002
PM 19083224
ER
PT J
AU Havens, PL
Mofenson, LM
AF Havens, Peter L.
Mofenson, Lynne M.
TI Routine Newborn HIV Testing: An Idea Whose Time Has Come In Reply
SO PEDIATRICS
LA English
DT Letter
C1 [Havens, Peter L.] Med Coll Wisconsin, Dept Pediat, Div Infect Dis, Milwaukee, WI 53226 USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Mat AIDS Branch, Rockville, MD USA.
RP Havens, PL (reprint author), Med Coll Wisconsin, Dept Pediat, Div Infect Dis, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2009
VL 123
IS 2
BP E363
EP E364
DI 10.1542/peds.2008-3681
PG 5
WC Pediatrics
SC Pediatrics
GA 397RB
UT WOS:000262678700091
ER
PT J
AU Wadhawan, R
Oh, W
Perritt, RL
McDonald, SA
Das, A
Poole, WK
Vohr, BR
Higgins, RD
AF Wadhawan, Rajan
Oh, William
Perritt, Rebecca L.
McDonald, Scott A.
Das, Abhik
Poole, W. Kenneth
Vohr, Betty R.
Higgins, Rosemary D.
TI Twin Gestation and Neurodevelopmental Outcome in Extremely Low Birth
Weight Infants
SO PEDIATRICS
LA English
DT Article
DE twins; neurodevelopmental impairment; extremely low birth weight infants
ID ASSISTED REPRODUCTION; NEONATAL OUTCOMES; PREGNANCIES; SINGLETONS
AB OBJECTIVE. The purpose of this work was to compare the risk-adjusted incidence of death or neurodevelopmental impairment at 18 to 22 months' corrected age between twin and singleton extremely low birth weight infants. We hypothesized that twin gestation is independently associated with increased risk of death or adverse neurodevelopmental outcomes at 18 to 22 months' corrected age in these infants.
METHODS. We conducted a retrospective study of inborn extremely low birth weight infants admitted to Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network units between 1997 and 2005, who either died or had follow-up data available at 18 to 22 months' corrected age. Neurodevelopmental impairment, the primary outcome variable, was defined as the presence of any 1 of the following: moderate or severe cerebral palsy, severe bilateral hearing loss, bilateral blindness, Bayley Mental Developmental Index or Psychomotor Developmental Index of < 70. Death was included with neurodevelopmental impairment as a composite outcome. Results were compared for both twins, twin A, twin B, same-gender twins, unlike-gender twins, and singleton infants. Logistic regression analysis was performed to control for demographic and clinical factors that were different among the groups.
RESULTS. The cohort of infants who either died or were assessed for neurodevelopmental impairment consisted of 7630 singleton infants and 1376 twins. Logistic regression adjusting for clinical and sociodemographic risk factors showed an increased risk of death or neurodevelopmental impairment for twins as a group when compared with the singletons. On analyzing twin A and B separately as well, risk of death or neurodevelopmental impairment was increased in both twin A and twin B.
CONCLUSIONS. Twin gestation in extremely low birth weight infants is associated with an independent increased risk of death or neurodevelopmental impairment at 18 to 22 months' corrected age compared with singleton-gestation infants. Both first- and second-born twins are at increased risk. Pediatrics 2009; 123: e220-e227
C1 [Wadhawan, Rajan] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
[Oh, William; Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Div Neonatol, Providence, RI USA.
[Wadhawan, Rajan; Oh, William; Perritt, Rebecca L.; McDonald, Scott A.; Das, Abhik; Poole, W. Kenneth; Vohr, Betty R.; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Wadhawan, R (reprint author), Univ S Florida, All Childrens Hosp, 880 6th St S,Suite 470, St Petersburg, FL 33701 USA.
EM wadhawar@allkids.org
FU NICHD [U10 HD53124, U10 HD53119, U10 HD53109, U10 HD53089, U10 HD40689,
U10 HD40521, U10 HD40498, U10 HD40492, U10 HD40461, U10 HD34216, U10
HD34167, U10 HD27904, U10 HD27881, U10 HD27880, U10 HD27871, U10
HD27856, U10 HD27853, U10 HD27851, U10 HD21415, U10 HD21397]; National
Institutes of Health [CCTS UL1 RR24128, CCTS UL1 RR24148, GCRC M01 RR30,
GCRC M01 RR32, GCRC M01 RR39, GCRC M01 RR44, GCRC M01 RR54, GCRC M01
RR59, GCRC M01 RR64, GCRC M01 RR70, GCRC M01 RR80, GCRC M01 RR633, GCRC
M01 RR750, GCRC M01 RR997, GCRC M01 RR1032, GCRC M01 RR2172, GCRC M01
RR2588]
FX This work was supported by grants from the NICHD (U10 HD53124, U10
HD53119, U10 HD53109, U10 HD53089, U10 HD40689, U10 HD40521, U10
HD40498, U10 HD40492, U10 HD40461, U10 HD34216, U10 HD34167, U10
HD27904, U10 HD27881, U10 HD27880, U10 HD27871, U10 HD27856, U10
HD27853, U10 HD27851, U10 HD21415, U10 HD21397, U10 HD21385, U10
HD21373, U10 HD21364, and U01 HD36790) and the National Institutes of
Health (CCTS UL1 RR24128, CCTS UL1 RR24148, GCRC M01 RR30, GCRC M01
RR32, GCRC M01 RR39, GCRC M01 RR44, GCRC M01 RR54, GCRC M01 RR59, GCRC
M01 RR64, GCRC M01 RR70, GCRC M01 RR80, GCRC M01 RR633, GCRC M01 RR750,
GCRC M01 RR997, GCRC M01 RR1032, GCRC M01 RR2172, GCRC M01 RR2588, GCRC
M01 RR2635, GCRC M01 RR6022, GCRC M01 RR7122, GCRC M01 RR8084, and GCRC
M01 RR16587).
NR 27
TC 18
Z9 19
U1 0
U2 3
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 FEB
PY 2009
VL 123
IS 2
BP E220
EP E227
DI 10.1542/peds.2008-1126
PG 8
WC Pediatrics
SC Pediatrics
GA 397RB
UT WOS:000262678700053
PM 19139085
ER
PT J
AU Trebak, M
Lemonnier, L
DeHaven, W
Wedel, B
Bird, G
Putney, JW
AF Trebak, Mohamed
Lemonnier, Loic
DeHaven, Wayne I.
Wedel, Barbara J.
Bird, Gary S.
Putney, James W., Jr.
TI Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation
of TRPC5 cation channels
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE Ion channels; Non-selective cation channels; TRPC5 channels;
Phosphatidylinositol 4; 5-bisphosphate; Phospholipase C
ID CAPACITATIVE CALCIUM-ENTRY; RECEPTOR POTENTIAL PROTEIN; FOCAL ADHESION
KINASE; TRANSIENT RECEPTOR; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE;
SENSITIVE POOLS; ION CHANNELS; WORTMANNIN; CELLS
AB The canonical transient receptor potential (TRPC) proteins have been recognized as key players in calcium entry pathways activated through phospholipase-C-coupled receptors. While it is clearly demonstrated that members of the TRPC3/6/7 subfamily are activated by diacylglycerol, the mechanism by which phospholipase C activates members of the TRPC1/4/5 subfamily remains a mystery. In this paper, we provide evidence for both negative and positive modulatory roles for membrane polyphosphoinositides in the regulation of TRPC5 channels. Depletion of polyphosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PIP(2)) through inhibition of phosphatidylinositol 4-kinase activates calcium entry and membrane currents in TRPC5-expressing but not in TRPC3- or TRPC7-expressing cells. Inclusion of polyphosphatidylinositol 4-phosphate or PIP(2), but not phosphatidylinositol 3,4,5-trisphosphate, in the patch pipette inhibited TRPC5 currents. Paradoxically, depletion of PIP(2) with a directed 5-phosphatase strategy inhibited TRPC5. Furthermore, when the activity of single TRPC5 channels was examined in excised patches, the channels were robustly activated by PIP(2). These findings indicate complex functions for regulation of TRPC5 by PIP(2), and we propose that membrane polyphosphoinositides may have at least two distinct functions in regulating TRPC5 channel activity.
C1 [Trebak, Mohamed; Lemonnier, Loic; DeHaven, Wayne I.; Wedel, Barbara J.; Bird, Gary S.; Putney, James W., Jr.] NIEHS, Dept Hlth & Human Serv, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), NIEHS, Dept Hlth & Human Serv, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM trebakm@mail.amc.edu; putney@niehs.nih.gov
RI Trebak, Mohamed/E-7405-2014
FU National Institute of Environmental Health Sciences; National Institutes
of Health [Z01 ES090087]
FX We are grateful to Dr. Lutz Birnbaumer who provided the plasmid
containing the cDNA for murine TRPC5 and Dr. Tamas Balla who provided
the constructs for plasma membrane targeting of PIP2
phosphatase. Drs. David Armstrong, Jerrel Yakel, Guillermo Vazquez,
Jason Mercer, and Jeremy Smyth read the manuscript and provided useful
criticism. This work was supported by the Intramural Research Program,
National Institute of Environmental Health Sciences, National Institutes
of Health, project number Z01 ES090087.
NR 68
TC 49
Z9 53
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD FEB
PY 2009
VL 457
IS 4
BP 757
EP 769
DI 10.1007/s00424-008-0550-1
PG 13
WC Physiology
SC Physiology
GA 397RO
UT WOS:000262680000005
PM 18665391
ER
PT J
AU Garbuzenko, OB
Saad, M
Betigeri, S
Zhang, M
Vetcher, AA
Soldatenkov, VA
Reimer, DC
Pozharov, VP
Minko, T
AF Garbuzenko, Olga B.
Saad, Maha
Betigeri, Seema
Zhang, Min
Vetcher, Alexandre A.
Soldatenkov, Viatcheslav A.
Reimer, David C.
Pozharov, Vitaly P.
Minko, Tamara
TI Intratracheal Versus Intravenous Liposomal Delivery of siRNA, Antisense
Oligonucleotides and Anticancer Drug
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE antisense oligonucleotides; imaging; liposomes; local lung delivery of
siRNA; lung cancer; pulmonary delivery
ID IN-VITRO CYTOTOXICITY; ANTITUMOR-ACTIVITY; CIRCULATION TIME; DNA
COMPLEXES; SOLID TUMOR; VIVO; PHARMACOKINETICS; DOXORUBICIN; EFFICACY;
SYSTEM
AB Purpose. To compare systemic intravenous and local intratracheal delivery of doxorubicin (DOX), antisense oligonucleotides (ASO) and small interfering RNA (siRNA).
Methods. "Neutral" and cationic liposomes were used to deliver DOX, ASO, and siRNA. Liposomes were characterized by dynamic light scattering, zeta-potential, and atomic force microscopy. Cellular internalization of DOX, ASO and siRNA was studied by confocal microscopy on human lung carcinoma cells. In vivo experiments were carried out on nude mice with an orthotopic model of human lung cancer.
Results. Liposomes provided for an efficient intracellular delivery of DOX, ASO, and siRNA in vitro. Intratracheal delivery of both types of liposomes in vivo led to higher peak concentrations and much longer retention of liposomes, DOX, ASO and siRNA in the lungs when compared with systemic administration. It was found that local intratracheal treatment of lung cancer with liposomal DOX was more efficient when compared with free and liposomal DOX delivered intravenously.
Conclusions. The present study outlined the clear advantages of local intratracheal delivery of liposomal drugs for the treatment of lung cancer when compared with systemic administration of the same drug.
C1 [Garbuzenko, Olga B.; Saad, Maha; Betigeri, Seema; Zhang, Min; Pozharov, Vitaly P.; Minko, Tamara] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, Piscataway, NJ 08854 USA.
[Vetcher, Alexandre A.] George Mason Univ, Natl Ctr Biodef & Infect Dis, Manassas, VA USA.
[Soldatenkov, Viatcheslav A.] Georgetown Univ, Med Ctr, Dept Radiat Med, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Reimer, David C.] Rutgers State Univ, Lab Anim Serv, Piscataway, NJ 08854 USA.
[Vetcher, Alexandre A.] Alcyon Bio Inc, Germantown, MD 20874 USA.
[Soldatenkov, Viatcheslav A.] NCI, DEA, SRLB, NIH, Bethesda, MD 20892 USA.
RP Minko, T (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, 160 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM minko@rci.rutgers.edu
FU NIH [CA100098, CA111766, CA074145]; National Cancer Institute
[LCD-23812-N]; American Lung Association of New Jersey
FX The research was supported in part by NIH grants CA100098, CA111766, and
CA074145 from the National Cancer Institute and by a LCD-23812-N grant
from the American Lung Association of New Jersey.
NR 44
TC 74
Z9 77
U1 3
U2 17
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
J9 PHARM RES-DORD
JI Pharm. Res.
PD FEB
PY 2009
VL 26
IS 2
BP 382
EP 394
DI 10.1007/s11095-008-9755-4
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 396CS
UT WOS:000262570400013
PM 18958402
ER
PT J
AU Kim, I
Kong, H
Lee, Y
Hong, SC
Han, JO
Jung, SH
Jung, YJ
Kim, YM
AF Kim, Inho
Kong, Hyesik
Lee, Younghyun
Hong, Sungchae
Han, Jungoh
Jung, Sunhwa
Jung, Yunjin
Kim, Young Mi
TI Dexamethasone 21-Sulfate Improves the Therapeutic Properties of
Dexamethasone Against Experimental Rat Colitis by Specifically
Delivering the Steroid to the Large Intestine
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE colon specific prodrug; dexamethasone; dexamethasone 21-sulfate;
inflammatory bowel disease; systemic adverse effect
ID INFLAMMATORY-BOWEL-DISEASE; APPENDED ALPHA-CYCLODEXTRIN; COLON-SPECIFIC
DELIVERY; DRUG-DELIVERY; POTENTIAL PRODRUGS; PREDNISOLONE; TRANSPORT;
SODIUM
AB Purpose. We investigated in vivo-colon targetability and therapeutic properties of DS against experimental rat colitis.
Methods. The systemic absorption and colonic delivery of D after oral administration of DS was analyzed by examining the concentration of drugs in the GI tract, plasma, urine and feces. Therapeutic activity of DS was determined using a TNBS-induced rat colitis model. Adrenal suppression by DS administration was evaluated by monitoring the concentration of ACTH and corticosterone in the plasma.
Results. DS administered orally was delivered efficiently to the large intestine resulting in D accumulation at the target site. In addition, DS was not detectable in the plasma and was detected very low in the urine after DS administration. The fecal and urinary recovery of D ( after DS administration) was much greater and less than that after D administration, suggesting that DS should exhibit enhanced therapeutic activity and reduced systemic side effects. Consistent with this notion, DS was more effective than D in healing rat colitis. Moreover, oral administration of either D or DS reduced the plasma corticosterone and ACTH levels from the normal levels, which is significantly greater for D.
Conclusion. DS is a promising colon specific prodrug that improves therapeutic properties of D
C1 [Kim, Inho; Lee, Younghyun; Hong, Sungchae; Han, Jungoh; Jung, Sunhwa; Jung, Yunjin; Kim, Young Mi] Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
[Kong, Hyesik] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Jung, YJ (reprint author), Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
EM jungy@pusan.ac.kr; ymikim@pusan.ac.kr
NR 20
TC 9
Z9 9
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
J9 PHARM RES-DORD
JI Pharm. Res.
PD FEB
PY 2009
VL 26
IS 2
BP 415
EP 421
DI 10.1007/s11095-008-9758-1
PG 7
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 396CS
UT WOS:000262570400016
PM 18958401
ER
PT J
AU Shukla, S
Zaher, H
Hartz, A
Bauer, B
Ware, JA
Ambudkar, SV
AF Shukla, Suneet
Zaher, Hani
Hartz, Anika
Bauer, Bjorn
Ware, Joseph A.
Ambudkar, Suresh V.
TI Curcumin Inhibits the Activity of ABCG2/BCRP1, a Multidrug
Resistance-Linked ABC Drug Transporter in Mice
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE ABC transporter; ABCG2; curcumin; multidrug resistance; sulfasalazine
ID BLOOD-BRAIN-BARRIER; GLYCOPROTEIN UP-REGULATION; NECROSIS-FACTOR-ALPHA;
BREAST-CANCER CELLS; P-GLYCOPROTEIN; PROTEIN ABCG2; MODULATION;
EXPRESSION; BIOAVAILABILITY; SULFASALAZINE
AB Purpose. To evaluate the in vivo efficacy of curcumin as an inhibitor of the multidrug-resistance-linked ATP Binding Cassette (ABC) drug transporter, ABCG2.
Methods. Photoaffinity labeling with [I-125]-iodoarylazidoprazosin was used to characterize the interaction of sulfasalazine, a substrate of the mouse ABCG2, with human ABCG2. In addition, the inhibitory effect of curcumin on ABCG2 was evaluated in brain capillaries from rats. Furthermore, the effect of curcumin on absorption of orally administered sulfasalazine in wild-type and abcg2(-/-)mice was also determined.
Results. Sulfasalazine interacted at the drug-substrate site(s) of human ABCG2. Curcumin inhibited ABCG2 activity at nanomolar concentrations at the rat blood-brain barrier in the ex vivo assay. Based on studies in wild type and abcg2(-/-) mice, we observed that oral curcumin increased C-max and relative bioavailability of sulfasalazine by selectively inhibiting ABCG2 function.
Conclusions. This study validates our previous in vitro results with human ABCG2 (Chearwae et al., Mol. Cancer Ther. 5:1995-2006, 2006) and provides the first in vivo evidence for the inhibition by curcumin of ABCG2-mediated efflux of sulfasalazine in mice. Based on these studies, we propose that non-toxic concentrations of curcumin may be used to enhance drug exposure when the rate-limiting step of drug absorption and/or tissue distribution is impacted by ABCG2.
C1 [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
[Zaher, Hani; Ware, Joseph A.] Pfizer Global Res & Dev, Dept Pharmacokinet Dynam & Metab, Ann Arbor, MI 48105 USA.
[Hartz, Anika] Univ Minnesota, Sch Med, Dept Biochem & Mol Biochem, Duluth, MN 55812 USA.
[Bauer, Bjorn] Univ Minnesota, Coll Pharm, Dept Pharmaceut Sci, Duluth, MN 55812 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
RI shukla, suneet/B-4626-2012
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. We thank Dr. Krishnamachary Nandigama for providing
ABCG2-expressing Hi-five insect cell crude membranes and George Leiman
for editorial assistance. The authors wish to acknowledge the
contribution of Joe Palandra of Pfizer Global Research and Development
for his assistance in determination of SASP bioanalysis and for the
input of Lisa Bernstein, Nonclinical Biostatistics, Genentech, Inc.
NR 43
TC 70
Z9 75
U1 1
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD FEB
PY 2009
VL 26
IS 2
BP 480
EP 487
DI 10.1007/s11095-008-9735-8
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 396CS
UT WOS:000262570400024
PM 18841445
ER
PT J
AU Radinger, M
Lotvall, J
AF Radinger, Madeleine
Loetvall, Jan
TI Eosinophil progenitors in allergy and asthma - Do they matter?
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Allergic inflammation; Eosinophil progenitor cells; Hematopoiesis;
Therapy; CCR3
ID IL-5 RECEPTOR-ALPHA; BONE-MARROW EOSINOPHILOPOIESIS; COLONY-STIMULATING
FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-3; NONATOPIC INTRINSIC
ASTHMATICS; MAJOR BASIC-PROTEIN; GUINEA-PIG MODEL; CD8(+) T-CELLS;
MURINE MODEL; CD34(+) CELLS
AB Allergic inflammation is associated with marked infiltration of eosinophils in affected tissues. The eosinophil is believed to be a key effector cells in allergen induced asthma pathogenesis. However, the role of eosinophils in the clinical manifestation of asthma has recently been questioned, since therapies directed against eosinophil infiltration (i.e. anti-interieukin-5) failed to improve clinical symptoms such as airways hyper-responsiveness (AHR) in patients with asthma. Although eosinophils in peripheral blood and the airways were largely depleted after anti-IL-5 treatment, residual eosinophilia in lung tissue persisted, which permits speculation that the remaining eosinophils may be sufficient to drive the asthma symptomatology. Furthermore, recent findings suggest that primitive eosinophil progenitor cells traffic from the bone marrow to sites of inflammation in response to allergen exposure. These progenitors may then differentiate in situ and thus provide an ongoing supply of mature pro-inflammatory cells and secretory mediators that augment the inflammatory response. In the present article, we will review the evidence for these findings, and discuss the rationale for targeting hematopoiesis and their migration pathways in the treatment of allergic diseases. Furthermore, this review will highlight the hypothesis that both IL-5- and CCR3-mediated signaling pathways may need to be targeted in order to control the inflammation and AHR associated with asthma. Published by Elsevier Inc.
C1 [Radinger, Madeleine] NIAID, Lab Allerg Dis, NIH, Mast Cell Biol Sect, Bethesda, MD 20892 USA.
[Loetvall, Jan] Univ Gothenburg, Lung Pharmacol Grp, Dept Internal Med Resp Med & Allergol, Sahlgrenska Acad, Gothenburg, Sweden.
RP Radinger, M (reprint author), NIAID, Lab Allerg Dis, NIH, Mast Cell Biol Sect, Bldg 10,Room 11C209,10 Ctr Dr,MSC1881, Bethesda, MD 20892 USA.
EM radingerm@niaid.nih.gov
OI Lotvall, Jan/0000-0001-9195-9249
FU Division of Intramural Research, National Institute of Allergy and
Infection Diseases
FX The authors are supported by the Swedish Heart and Lung Foundation. Dr
Madeleine RAdinger is in part supported by the Division of Intramural
Research, National Institute of Allergy and Infection Diseases.
NR 150
TC 33
Z9 33
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD FEB
PY 2009
VL 121
IS 2
BP 174
EP 184
DI 10.1016/j.pharmthera.2008.10.008
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 419RD
UT WOS:000264236100005
PM 19059433
ER
PT J
AU Minh, DDL
Adib, AB
AF Minh, David D. L.
Adib, Artur B.
TI Path integral analysis of Jarzynski's equality: Analytical results
SO PHYSICAL REVIEW E
LA English
DT Article
DE Brownian motion; harmonic oscillators; nonequilibrium thermodynamics
ID FREE-ENERGY DIFFERENCES
AB We apply path integrals to study nonequilibrium work theorems in the context of Brownian dynamics, deriving in particular the equations of motion governing the most typical and most dominant trajectories. For the analytically soluble cases of a moving harmonic potential and a harmonic oscillator with a time-dependent natural frequency, we find such trajectories, evaluate the work-weighted propagators, and validate Jarzynski's equality.
C1 [Minh, David D. L.; Adib, Artur B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Minh, DDL (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM daveminh@gmail.com; adiba@mail.nih.gov
RI Minh, David/A-4655-2009
OI Minh, David/0000-0002-4802-2618
FU NIH; NIDDK
FX The authors are indebted to Attila Szabo for numerous discussions. This
research was supported by the Intramural Research Program of the NIH,
NIDDK.
NR 16
TC 12
Z9 12
U1 1
U2 5
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 FEB
PY 2009
VL 79
IS 2
AR 021122
DI 10.1103/PhysRevE.79.021122
PG 5
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 413QJ
UT WOS:000263807300029
PM 19391721
ER
PT J
AU Loftus, SK
Antonellis, A
Matera, I
Renaud, G
Baxter, LL
Reid, D
Wolfsberg, TG
Chen, YD
Wang, CW
Prasad, MK
Bessling, SL
McCallion, AS
Green, ED
Bennett, DC
Pavan, WJ
AF Loftus, Stacie K.
Antonellis, Anthony
Matera, Ivana
Renaud, Gabriel
Baxter, Laura L.
Reid, Duncan
Wolfsberg, Tyra G.
Chen, Yidong
Wang, ChenWei
Prasad, Megana K.
Bessling, Seneca L.
McCallion, Andrew S.
Green, Eric D.
Bennett, Dorothy C.
Pavan, William J.
CA NISC Comparative Sequencing
TI Gpnmb is a melanoblast-expressed, MITF-dependent gene
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE Gpnmb; Mitf; Sox10; melanoblast; melanocyte; melanoma
ID MELANOCYTE-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR;
DOPACHROME-TAUTOMERASE; EMBRYONIC-DEVELOPMENT; WAARDENBURG-SYNDROME;
MALIGNANT-MELANOMA; MOUSE MELANOCYTES; SOX10 MUTATION; DBA/2J MICE;
MICROPHTHALMIA
AB Expression profile analysis clusters Gpnmb with known pigment genes, Tyrp1, Dct, and Si. During development, Gpnmb is expressed in a pattern similar to Mitf, Dct and Si with expression vastly reduced in Mitf mutant animals. Unlike Dct and Si, Gpnmb remains expressed in a discrete population of caudal melanoblasts in Sox10-deficient embryos. To understand the transcriptional regulation of Gpnmb we performed a whole genome annotation of 2,460,048 consensus MITF binding sites, and cross-referenced this with evolutionarily conserved genomic sequences at the GPNMB locus. One conserved element, GPNMB-MCS3, contained two MITF consensus sites, significantly increased luciferase activity in melanocytes and was sufficient to drive expression in melanoblasts in vivo. Deletion of the 5'-most MITF consensus site dramatically reduced enhancer activity indicating a significant role for this site in Gpnmb transcriptional regulation. Future analysis of the Gpnmb locus will provide insight into the transcriptional regulation of melanocytes, and Gpnmb expression can be used as a marker for analyzing melanocyte development and disease progression.
C1 [Loftus, Stacie K.; Antonellis, Anthony; Matera, Ivana; Renaud, Gabriel; Baxter, Laura L.; Reid, Duncan; Wolfsberg, Tyra G.; Wang, ChenWei; Green, Eric D.; Pavan, William J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Matera, Ivana] Inst G Gaslini, Genet Mol Lab, Genoa, Italy.
[Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Green, Eric D.; NISC Comparative Sequencing] NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Prasad, Megana K.; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Bennett, Dorothy C.] St Georges Univ London, Div Basic Med Sci, London, England.
RP Loftus, SK (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM sloftus@mail.nih.gov
RI Bennett, Dorothy/C-2418-2008
OI Bennett, Dorothy/0000-0002-3639-7527
FU National Human Genome Research Institute's (NHGRI) Intramural Research
Program
FX We would like to acknowledge Shih-Queen Lee-Lin for expert technical
assistance, Abdel Elkahloun for technical assistance with microarray
hybridizations, Julia Feckes for graphics assistance and NIH Intramural
Sequencing Center (NISC) for generating sequence data. Handling of mice
was performed in accordance with NIH guidelines under animal care and
use mouse protocol G94-7. All zebrafish work was performed under
protocols approved by the Johns Hopkins University Animal Care and Use
Committee. This work was supported in part by the National Human Genome
Research Institute's (NHGRI) Intramural Research Program.
NR 49
TC 25
Z9 28
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD FEB
PY 2009
VL 22
IS 1
BP 99
EP 110
DI 10.1111/j.1755-148X.2008.00518.x
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 395GV
UT WOS:000262513500014
PM 18983539
ER
PT J
AU Arnheiter, H
AF Arnheiter, Heinz
TI 'A response to 'Mammalian paramutation: a tail's tale?'- a commentary by
H. Arnheiter on our paramutation paper'- a reply
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Letter
ID INHERITANCE; MOUSE
C1 Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD USA.
RP Arnheiter, H (reprint author), Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD USA.
EM ha3p@nih.gov
NR 3
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD FEB
PY 2009
VL 22
IS 1
BP 142
EP 143
DI 10.1111/j.1755-148X.2008.00522.x
PG 2
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 395GV
UT WOS:000262513500022
ER
PT J
AU Kovalchuk, I
Lyudvikova, Y
Volgina, M
Reed, BM
AF Kovalchuk, Irina
Lyudvikova, Yelena
Volgina, Mariam
Reed, Barbara M.
TI Medium, container and genotype all influence in vitro cold storage of
apple germplasm
SO PLANT CELL TISSUE AND ORGAN CULTURE
LA English
DT Article
DE In vitro storage; Malus domestica; Malus sieversii; Micropropagation;
Germplasm storage
ID SLOW-GROWTH; INVITRO; SURVIVAL; SHOOTS
AB The goal of this study was to evaluate the in vitro storage of apple germplasm by screening a range of genotypes followed by more comprehensive testing of multiple parameters on two genotypes of differing species, Malus domestica cultivar Grushovka Vernenskaya and wild Malus sieversii selection TM-6. Stored plants were rated on a 6 point scale (0 low to 5 high) for plant appearance at 3 month intervals after storage at 4A degrees C. Combinations of carbon source (sucrose and/or mannitol), nitrate nitrogen content (25, 50 or 100%) and plant growth regulators (ABA, BAP, IBA) were studied in three types of containers (tissue culture bags, test tubes or jars). An initial screen of 16 genotypes stored in tissue culture bags indicated that plantlets could be stored at 4A degrees C for 9-14 months without subculture on standard 3% sucrose Murashige and Skoog (1962) (MS) medium with no plant growth regulators (PGRs). In subsequent in-depth studies on the two genotypes, ANOVA indicated highly significant interactions of medium, container and genotype. 'Grushovka Vernenskaya' shoots with no PGRs and 3% sucrose remained viable (ratings of a parts per thousand yen1) for 21 months of storage in bags. Storage on reduced nitrogen (MS with 25% nitrogen), PGRs, and 3% sucrose kept 'Grushovka Vernenskaya' shoot condition rated > 2 at 21 months. Addition of 0.5 or 1 mg(-1) abscisic acid (ABA) also improved plant ratings at 21 months. The longest storage for 'Grushovka Vernenskaya' was 33-39 months with PGRs and 3% sucrose in either tubes or jars. Addition of abscisic acid (ABA) to the medium did not improve storage of plantlets in jars and tubes at 15 months. TM-6 stored best in tubes on 3% sucrose with PGRs or in jars on 2% mannitol and 2% sucrose. Overall it appears that cold storage of apple shoot cultures can be successful for 21 months in tissue culture bags with 25% MS nitrate nitrogen, 3% sucrose, and no PGRs or for 33 months in jars or tubes on MS with 3% sucrose and PGRs. Preliminary RAPD analysis found no significant differences between plants stored for 39 months and non-stored controls.
C1 [Reed, Barbara M.] USDA ARS, Natl Clonal Germplasm Repository, Corvallis, OR 97333 USA.
[Kovalchuk, Irina; Lyudvikova, Yelena; Volgina, Mariam] Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Alma Ata 050040, Kazakhstan.
RP Reed, BM (reprint author), USDA ARS, Natl Clonal Germplasm Repository, 33447 Peoria Rd, Corvallis, OR 97333 USA.
EM kovalchuk_i_u@mail.ru; Barbara.Reed@ars.usda.gov
OI Reed, Barbara/0000-0003-0079-8473
FU International Science and Technology Center [K428]; USDA-ARS CRIS
[5358-21000-033D]
FX This research was supported by funds from the International Science and
Technology Center Grant K428 and USDA-ARS CRIS project 5358-21000-033D.
NR 20
TC 24
Z9 26
U1 1
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6857
J9 PLANT CELL TISS ORG
JI Plant Cell Tissue Organ Cult.
PD FEB
PY 2009
VL 96
IS 2
BP 127
EP 136
DI 10.1007/s11240-008-9468-8
PG 10
WC Biotechnology & Applied Microbiology; Plant Sciences
SC Biotechnology & Applied Microbiology; Plant Sciences
GA 389JM
UT WOS:000262088700002
ER
PT J
AU Sethi, AJ
Angerer, RC
Angerer, LM
AF Sethi, Aditya J.
Angerer, Robert C.
Angerer, Lynne M.
TI Gene Regulatory Network Interactions in Sea Urchin Endomesoderm
Induction
SO PLOS BIOLOGY
LA English
DT Article
ID NUCLEAR BETA-CATENIN; ENDODERM DIFFERENTIATION; CELL FATE;
MICROMERE-DESCENDANTS; EMBRYO; SPECIFICATION; EXPRESSION; BLASTOMERES;
XENOPUS; AXIS
AB A major goal of contemporary studies of embryonic development is to understand large sets of regulatory changes that accompany the phenomenon of embryonic induction. The highly resolved sea urchin pregastrular endomesoderm-gene regulatory network (EM-GRN) provides a unique framework to study the global regulatory interactions underlying endomesoderm induction. Vegetal micromeres of the sea urchin embryo constitute a classic endomesoderm signaling center, whose potential to induce archenteron formation from presumptive ectoderm was demonstrated almost a century ago. In this work, we ectopically activate the primary mesenchyme cell-GRN (PMC-GRN) that operates in micromere progeny by misexpressing the micromere determinant Pmar1 and identify the responding EM-GRN that is induced in animal blastomeres. Using localized loss-of-function analyses in conjunction with expression of endo16, the molecular definition of micromere-dependent endomesoderm specification, we show that the TGF beta cytokine, ActivinB, is an essential component of this induction in blastomeres that emit this signal, as well as in cells that respond to it. We report that normal pregastrular endomesoderm specification requires activation of the Pmar1-inducible subset of the EM-GRN by the same cytokine, strongly suggesting that early micromere-mediated endomesoderm specification, which regulates timely gastrulation in the sea urchin embryo, is also ActivinB dependent. This study unexpectedly uncovers the existence of an additional uncharacterized micromere signal to endomesoderm progenitors, significantly revising existing models. In one of the first network-level characterizations of an intercellular inductive phenomenon, we describe an important in vivo model of the requirement of ActivinB signaling in the earliest steps of embryonic endomesoderm progenitor specification.
C1 [Sethi, Aditya J.; Angerer, Robert C.; Angerer, Lynne M.] Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD USA.
RP Angerer, LM (reprint author), Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD USA.
EM langerer@mail.nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health [NIH-GM25553]
FX This work was supported initially by a grant to RCA (NIH-GM25553) and
recently by the Intramural Research Program of the National Institute of
Dental and Craniofacial Research, 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 54
TC 22
Z9 22
U1 0
U2 9
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 FEB
PY 2009
VL 7
IS 2
BP 248
EP 264
AR e1000029
DI 10.1371/journal.pbio.1000029
PG 17
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 410SZ
UT WOS:000263599900007
PM 19192949
ER
PT J
AU Bruzzone, R
Dubois-Dalcq, M
Grau, GE
Griffin, DE
Kristensson, K
AF Bruzzone, Roberto
Dubois-Dalcq, Monique
Grau, Georges E.
Griffin, Diane E.
Kristensson, Krister
TI Infectious Diseases of the Nervous System and Their Impact in Developing
Countries
SO PLOS PATHOGENS
LA English
DT Editorial Material
ID HUMAN AFRICAN TRYPANOSOMIASIS; CEREBRAL MALARIA; HIV; PATHOGENESIS;
VIRUSES; TROPISM; BRAIN
C1 [Bruzzone, Roberto] Univ Hong Kong, Pasteur Res Ctr, Hong Kong, Hong Kong, Peoples R China.
[Dubois-Dalcq, Monique] NINDS, NIH, Bethesda, MD 20892 USA.
[Grau, Georges E.] Univ Sidney, Dept Pathol, Sydney, NSW, Australia.
[Grau, Georges E.] Bosch Inst, Sydney, NSW, Australia.
[Griffin, Diane E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Kristensson, Krister] Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
RP Bruzzone, R (reprint author), Univ Hong Kong, Pasteur Res Ctr, Hong Kong, Hong Kong, Peoples R China.
EM bruzzone@hku.hk
RI Bruzzone, Roberto/C-4719-2009; Grau, Georges/D-7690-2014
OI Bruzzone, Roberto/0000-0003-4373-1447; Grau, Georges/0000-0002-0442-0462
FU Arthritis Research UK; NINDS NIH HHS [R01 NS038932]; Wellcome Trust
NR 22
TC 7
Z9 7
U1 0
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 FEB
PY 2009
VL 5
IS 2
AR e1000199
DI 10.1371/journal.ppat.1000199
PG 3
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 415IR
UT WOS:000263928000001
PM 19247436
ER
PT J
AU Lim, JK
Lisco, A
McDermott, DH
Huynh, L
Ward, JM
Johnson, B
Johnson, H
Pape, J
Foster, GA
Krysztof, D
Follmann, D
Stramer, SL
Margolis, LB
Murphy, PM
AF Lim, Jean K.
Lisco, Andrea
McDermott, David H.
Huynh, Linda
Ward, Jerrold M.
Johnson, Bernard
Johnson, Hope
Pape, John
Foster, Gregory A.
Krysztof, David
Follmann, Dean
Stramer, Susan L.
Margolis, Leonid B.
Murphy, Philip M.
TI Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with
West Nile Virus in Man
SO PLOS PATHOGENS
LA English
DT Article
ID UNITED-STATES; HEPATITIS-C; RNASE-L; 2'-5'-OLIGOADENYLATE SYNTHETASE;
FLAVIVIRUS RESISTANCE; ENZYME-ACTIVITY; BLOOD-DONORS; NEW-YORK;
INTERFERON; SUSCEPTIBILITY
AB West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2'-5' oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The 'A' allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2-2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the 'A' allele (P, 0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans.
C1 [Lim, Jean K.; McDermott, David H.; Huynh, Linda; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Lisco, Andrea; Margolis, Leonid B.] NICHHD, Sect Intercellular Interact, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Bernard; Johnson, Hope] Illinois Dept Publ Hlth, Div Labs, Chicago, IL USA.
[Pape, John] Colorado Dept Publ Hlth & Environm, Denver, CO USA.
[Foster, Gregory A.; Krysztof, David; Stramer, Susan L.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Follmann, Dean] Amer Red Cross, Gaithersburg, MD USA.
RP Lim, JK (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pmm@nih.gov
OI McDermott, David/0000-0001-6978-0867
FU Intramural Research Program of the NIH/NIAID/DIR
FX This research was supported by the Intramural Research Program of the
NIH/NIAID/DIR.
NR 44
TC 98
Z9 101
U1 1
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 FEB
PY 2009
VL 5
IS 2
AR e1000321
DI 10.1371/journal.ppat.1000321
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 415IR
UT WOS:000263928000012
PM 19247438
ER
PT J
AU Buice, MA
Cowan, JD
AF Buice, Michael A.
Cowan, Jack D.
TI Statistical mechanics of the neocortex
SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
LA English
DT Review
DE Statistical mechanics; Field theory; Neocortex; Criticality; Scaling
laws; Directed percolation; Critical branching; Spike model; Epilepsy;
Random and rhythmic activity
ID FOREST-FIRE MODEL; SELF-ORGANIZED CRITICALITY; REGGEON FIELD-THEORY;
RANGE TEMPORAL CORRELATIONS; NEURAL SPIKE TRAIN; PHASE-TRANSITIONS;
RENORMALIZATION-GROUP; STOCHASTIC RESONANCE; SYNAPTIC DEPRESSION;
CRITICAL-BEHAVIOR
AB We analyze neocortical dynamics using field theoretic methods for non-equilibrium statistical processes. Assuming the dynamics is Markovian, we introduce a model that describes both neural fluctuations and responses to stimuli. We show that at low spiking rates, neocortical activity exhibits a dynamical phase transition which is in the universality class of directed percolation (DP). Because of the high density and large spatial extent of neural interactions, there is a "mean field" region in which the effects of fluctuations are negligible. However as the generation and decay of spiking activity becomes balanced, there is a crossover into the critical fluctuation driven DP region, consistent with measurements in neocortical slice preparations. From the perspective of theoretical neuroscience, the principal contribution of this work is the formulation of a theory of neural activity that goes beyond the mean-field approximation and incorporates the effects of fluctuations and correlations in the critical region. This theory shows that the scaling laws found in many measurements of neocortical activity, in anesthetized, normal and epileptic neocortex, are consistent with the existence of DP and related phase transitions at a critical point. It also shows how such properties lead to a model of the origins of both random and rhythmic brain activity. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Cowan, Jack D.] Univ Chicago, Dept Math, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
[Buice, Michael A.] NIH NIDDK LBM, Bethesda, MD 20892 USA.
RP Cowan, JD (reprint author), Univ Chicago, Dept Math, Gordon Ctr Integrat Sci, E505B,929 E 57th St, Chicago, IL 60637 USA.
EM cowan@math.uchicago.edu
FU Intramural NIH HHS
NR 142
TC 32
Z9 32
U1 2
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6107
J9 PROG BIOPHYS MOL BIO
JI Prog. Biophys. Mol. Biol.
PD FEB-MAY
PY 2009
VL 99
IS 2-3
BP 53
EP 86
DI 10.1016/j.pbiomolbio.2009.07.003
PG 34
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 502NX
UT WOS:000270468300001
PM 19695282
ER
PT J
AU Juruena, MF
Ottoni, GL
Machado-Vieira, R
Carneiro, RM
Weingarthner, N
Marquardt, AR
Fleig, SS
Broilo, L
Busnello, EA
AF Juruena, M. F.
Ottoni, G. L.
Machado-Vieira, R.
Carneiro, R. M.
Weingarthner, N.
Marquardt, A. R.
Fleig, S. S.
Broilo, L.
Busnello, E. A.
TI Bipolar I and II disorder residual symptoms: Oxcarbazepine and
carbamazepine as add-on treatment to lithium in a double-blind,
randomized trial
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Bipolar disorder; Carbamazepine; Clinical trial; Lithium; Oxcarbazepine;
Residual symptoms
ID MANIA; GUIDELINES; MOOD
AB Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC (n = 26) or CBZ (n = 26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint (p<0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 (p<0.05) and from baseline to week 8 (p<0.001), except YMRS (p<0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Juruena, M. F.] Kings Coll London, Inst Psychiat, Sect Neurobiol Mood Disorders, London WC2R 2LS, England.
[Juruena, M. F.; Ottoni, G. L.; Machado-Vieira, R.; Carneiro, R. M.; Weingarthner, N.; Marquardt, A. R.; Fleig, S. S.; Broilo, L.; Busnello, E. A.] Fed Univ Healthy Sci Porto Alegre UFCSPA, Dept Psychiat, Affect Disorders Unit, Porto Alegre, RS, Brazil.
[Juruena, M. F.] Bethlem Royal & Maudsley Hosp, Natl Affect Disorders Uni, Affect Disorders Unit Lab, Beckenham, Kent, England.
[Machado-Vieira, R.] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Juruena, MF (reprint author), Av Candido Pereira Lima 416, BR-14040250 Ribeirao Preto, Brazil.
EM M.Juruena@iop.kcl.ac.uk
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Juruena, Mario/D-5571-2009;
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Juruena,
Mario/0000-0001-8558-3396; Juruena, Mario F./0000-0002-4063-2278
FU Novartis Company; 2003-07 CAPES Fellowship Award; 2006-08 NARSAD Young
Investigator Award; 2007 NIHR Biomedical Research Centre at South London
and Maudsley NHS Trust & Institute of Psychiatry (Kings' College London)
FX This trial was sponsored by Novartis Company. M.F. Juruena received
2003-07 CAPES Fellowship Award; 2006-08 NARSAD Young Investigator Award;
and 2007 NIHR Biomedical Research Centre at South London and Maudsley
NHS Trust & Institute of Psychiatry (Kings' College London). We wish to
thank F. Pereira for carrying out the statistical analyses of this
trial.
NR 32
TC 21
Z9 22
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD FEB 1
PY 2009
VL 33
IS 1
BP 94
EP 99
DI 10.1016/j.pnpbp.2008.10.012
PG 6
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 405GX
UT WOS:000263212200018
PM 19007842
ER
PT J
AU Zhang, QM
Peng, H
Gao, F
Liu, YW
Cheng, H
Thompson, J
Gao, GF
AF Zhang, Qiangmin
Peng, Hao
Gao, Feng
Liu, Yiwei
Cheng, Hao
Thompson, John
Gao, George F.
TI Structural insight into the catalytic mechanism of gluconate
5-dehydrogenase from Streptococcus suis: Crystal structures of the
substrate-free and quaternary complex enzymes
SO PROTEIN SCIENCE
LA English
DT Article
DE Streptococcus suis serotype 2; gluconate 5-dehydrogenase (Ga5DH);
quaternary complex; SDR enzymes; catalytic mechanism
ID LUNG CARBONYL REDUCTASE; ESCHERICHIA-COLI; HYDROXYSTEROID DEHYDROGENASE;
3-DIMENSIONAL STRUCTURE; GLUCONOBACTER-OXYDANS; ANGSTROM RESOLUTION;
SEQUENCE-ANALYSIS; TERNARY COMPLEX; CRYSTALLIZATION; MUTAGENESIS
AB Gluconate 5-dehydrogenase (Ga5DH) is an NADP(H)-dependent enzyme that catalyzes a reversible oxidoreduction reaction between D-gluconate and 5-keto-D-gluconate, thereby regulating the flux of this important carbon and energy source in bacteria. Despite the considerable amount of physiological and biochemical knowledge of Ga5DH, there is little physical or structural information available for this enzyme. To this end, we herein report the crystal structures of Ga5DH from pathogenic Streptococcus suis serotype 2 in both substrate-free and liganded (NADP1/D-gluconate/metalion) quaternary complex forms at 2.0 angstrom resolution. Structural analysis reveals that Ga5DH adopts a protein fold similar to that found in members of the short chain dehydrogenase/reductase (SDR) family, while the enzyme itself represents a previously uncharacterized member of this family. In solution, Ga5DH exists as a tetramer that comprised four identical similar to 29 kDa subunits. The catalytic site of Ga5DH shows considerable architectural similarity to that found in other enzymes of the SDR family, but the S. suis protein contains an additional residue (Arg104) that plays an important role in the binding and orientation of substrate. The quaternary complex structure provides the first clear crystallographic evidence for the role of a catalytically important serine residue and also reveals an amino acid tetrad RSYK that differs from the SYK triad found in the majority of SDR enzymes. Detailed analysis of the crystal structures reveals important contributions of Ca(2+) ions to active site formation and of specific residues at the C-termini of subunits to tetramer assembly. Because Ga5DH is a potential target for therapy, our findings provide insight not only of catalytic mechanism, but also suggest a target of structure-based drug design.
C1 [Zhang, Qiangmin; Peng, Hao; Gao, Feng; Liu, Yiwei; Cheng, Hao; Gao, George F.] Chinese Acad Sci, Inst Microbiol, Beijing 100101, Peoples R China.
[Zhang, Qiangmin; Cheng, Hao] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
[Gao, Feng] China Agr Univ, Coll Life Sci, Beijing 100094, Peoples R China.
[Thompson, John] NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH,DHHS, Bethesda, MD 20892 USA.
[Gao, George F.] Chinese Acad Sci, China Japan Joint Lab Mol Immunol & Mol Immunol, Inst Microbiol, Beijing 100101, Peoples R China.
RP Gao, GF (reprint author), Chinese Acad Sci, Inst Microbiol, Datun Rd, Beijing 100101, Peoples R China.
EM gaof@im.ac.cn
FU The National Basic Research Program [973]; Ministry of Science and
Technology of China ( MOST); [2005CB523001, 2006BAD06A04]; National Key
Technologies R D Program; Ministry of Science and Technology of China (
MOST);; National Natural Science Foundation of China ( NSFC); [30770024,
30525010]; Intramural Research Program of the NIDCR; National Institutes
of Health
FX The National Basic Research Program ( 973), Ministry of Science and
Technology of China ( MOST); Grant number: 2005CB523001; Grant sponsor:
National Key Technologies R& D Program, Ministry of Science and
Technology of China ( MOST); Grant number: 2006BAD06A04; Grant sponsor:
National Natural Science Foundation of China ( NSFC); Grant numbers:
30770024, 30525010; Grant sponsor: Intramural Research Program of the
NIDCR, National Institutes of Health.
NR 33
TC 10
Z9 11
U1 2
U2 11
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 FEB
PY 2009
VL 18
IS 2
BP 294
EP 303
DI 10.1002/pro.32
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 429SX
UT WOS:000264941500005
PM 19177572
ER
PT J
AU Lountos, GT
Austin, BP
Nallamsetty, S
Waugh, DS
AF Lountos, George T.
Austin, Brian P.
Nallamsetty, Sreedevi
Waugh, David S.
TI Atomic resolution structure of the cytoplasmic domain of Yersinia pestis
YscU, a regulatory switch involved in type III secretion
SO PROTEIN SCIENCE
LA English
DT Article
DE type III secretion; Yersinia; molecular switch; atomic resolution; YscU
ID SUBSTRATE-SPECIFICITY; SYSTEM; EXPORT; CLEAVAGE; MODEL; FLHB;
PSEUDOTUBERCULOSIS; INJECTISOME; COMPLEXES; MECHANISM
AB Crystal structures of cleaved and uncleaved forms of the YscU cytoplasmic domain, an essential component of the type III secretion system (T3SS) in Yersinia pestis, have been solved by single-wavelength anomolous dispersion and refined with X-ray diffraction data extending up to atomic resolution (1.13 angstrom). These crystallographic studies provide structural insights into the conformational changes induced upon auto-cleavage of the cytoplasmic domain of YscU. The structures indicate that the cleaved fragments remain bound to each other. The conserved NPTH sequence that contains the site of the N263-P264 peptide bond cleavage is found on a beta-turn which, upon cleavage, undergoes a major reorientation of the loop away from the catalytic N263, resulting in altered electrostatic surface features at the site of cleavage. Additionally, a significant conformational change was observed in the N-terminal linker regions of the cleaved and noncleaved forms of YscU which may correspond to the molecular switch that influences substrate specificity. The YscU structures determined here also are in good agreement with the auto-cleavage mechanism described for the flagellar homolog FlhB and E. coli EscU.
C1 [Lountos, George T.; Austin, Brian P.; Nallamsetty, Sreedevi; Waugh, David S.] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM waughd@ncifcrf.gov
RI Lountos, George/B-3983-2015
FU Intramural NIH HHS
NR 32
TC 29
Z9 29
U1 0
U2 4
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 FEB
PY 2009
VL 18
IS 2
BP 467
EP 474
DI 10.1002/pro.56
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 429SX
UT WOS:000264941500021
PM 19165725
ER
PT J
AU Abou Jamra, R
Georgi, A
Suliman, H
Klein, K
Villela, AW
Schulze, TG
Propping, P
Cichon, S
Rietschel, M
Nothen, MM
Schumacher, J
AF Abou Jamra, Rami
Georgi, Alexander
Suliman, Husam
Klein, Katrin
Villela, Angela Wolf
Schulze, Thomas G.
Propping, Peter
Cichon, Sven
Rietschel, Marcella
Noethen, Markus M.
Schumacher, Johannes
TI No association between the D-aspartate oxidase locus and schizophrenia
SO PSYCHIATRIC GENETICS
LA English
DT Article
ID LINKAGE
C1 [Abou Jamra, Rami; Suliman, Husam; Klein, Katrin; Villela, Angela Wolf; Propping, Peter; Noethen, Markus M.; Schumacher, Johannes] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany.
[Cichon, Sven; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53111 Bonn, Germany.
[Georgi, Alexander; Schulze, Thomas G.; Rietschel, Marcella] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Schumacher, Johannes] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
RP Abou Jamra, R (reprint author), Univ Bonn, Inst Human Genet, Wilhelmstr 31, D-53111 Bonn, Germany.
EM rami.aboujamra@uni-bonn.de
RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher,
Johannes/F-4970-2015
OI Georgi, Alexander/0000-0002-1499-8524; Cichon, Sven/0000-0002-9475-086X;
Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399;
Nothen, Markus/0000-0002-8770-2464; Schumacher,
Johannes/0000-0001-9217-6457
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8829
J9 PSYCHIAT GENET
JI Psychiatr. Genet.
PD FEB
PY 2009
VL 19
IS 1
BP 56
EP 56
DI 10.1097/YPG.0b013e3283118739
PG 1
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 399SZ
UT WOS:000262820900009
ER
PT J
AU Cirulli, F
Francia, N
Branchi, I
Antonucci, MT
Aloe, L
Suomi, SJ
Alleva, E
AF Cirulli, Francesca
Francia, Nadia
Branchi, Igor
Antonucci, Maria Teresa
Aloe, Luigi
Suomi, Stephen J.
Alleva, Enrico
TI Changes in plasma levels of BDNF and NGF reveal a gender-selective
vulnerability to early adversity in rhesus macaques
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Nerve growth actor (NGF); Brain-derived neurotrophic factor (BDNF);
Depression; Vulnerability; Gender; Non-human primates
ID NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR BDNF; DEPRESSED-PATIENTS;
RAT-BRAIN; SERUM CONCENTRATIONS; MATERNAL SEPARATION; FACTOR EXPRESSION;
HUMAN PLATELETS; STRESS; GENE
AB Early stressful events can increase vulnerability for psychopathology, although knowledge on the effectors is still limited. Here we tested the hypothesis that peripheral levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are involved in the response to stress and in the pathophysiology of anxiety and depression, might be affected in a non-human primate model of adverse rearing. Mates and females rhesus macaques reared with their mothers (MR) or in peer-only groups (PR) were used as experimental subjects. BDNF, NGF, adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) were determined at baseline on postnatal days (PND) 14, 30 and 60 by means of specific ELISA and RIA procedures. In addition, behavior was assessed on PND 7, 14, 21, 30 (Brazelton test) and 60 (home cage observation). Data indicate gender differences in basal levels of BDNF throughout development. Peer-rearing increased significantly BDNF levels only in females. In addition, while all peer-reared subjects showed high levels of stereotypies and self-directed behaviors, behavioral passivity was selectively increased in females. By contrast, NGF levels were increased in response to peer-rearing only in mates, and correlated positively with other "classic" endocrine responses to stress, such as cortisol and GH. Our data identify BDNF and NGF as neuroendocrine markers underlying differential responses to maternal deprivation in mates and females rhesus macaques. The selective changes in BDNF levels in females could help explain the greater vulnerability to mood disorders of this gender reported in humans. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Cirulli, Francesca; Francia, Nadia; Branchi, Igor; Alleva, Enrico] Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, I-00161 Rome, Italy.
[Antonucci, Maria Teresa; Aloe, Luigi] CNR, EBRI, Inst Neurobiol & Mol Med, I-00143 Rome, Italy.
[Suomi, Stephen J.] NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA.
RP Cirulli, F (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy.
EM francesca.cirulli@iss.it
RI Cirulli, Francesca/B-1581-2013; Alleva, Enrico/B-1630-2013;
OI cirulli, francesca/0000-0001-9440-1873; Branchi,
Igor/0000-0003-4484-3598
FU Intramural NIH HHS [Z01 HD001106-24]
NR 58
TC 46
Z9 47
U1 0
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD FEB
PY 2009
VL 34
IS 2
BP 172
EP 180
DI 10.1016/j.psyneuen.2008.08.020
PG 9
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA 408JM
UT WOS:000263431300002
PM 18849121
ER
PT J
AU Lane, RD
Waldstein, SR
Chesney, MA
Jennings, JR
Lovallo, WR
Kozel, PJ
Rose, RM
Drossman, DA
Schneiderman, N
Thayer, JF
Cameron, OG
AF Lane, Richard D.
Waldstein, Shari R.
Chesney, Margaret A.
Jennings, J. Richard
Lovallo, William R.
Kozel, Peter J.
Rose, Robert M.
Drossman, Douglas A.
Schneiderman, Neil
Thayer, Julian F.
Cameron, Oliver G.
TI The Rebirth of Neuroscience in Psychosomatic Medicine, Part I:
Historical Context, Methods, and Relevant Basic Science
SO PSYCHOSOMATIC MEDICINE
LA English
DT Review
DE neuroscience; brain imaging; information transfer systems; autonomic
nervous system; neuroendocrinology; psychoneuroimmunology
ID ANTERIOR CINGULATE CORTEX; CORTICOTROPIN-RELEASING-FACTOR;
BLOOD-PRESSURE REACTIVITY; INDUCED SICKNESS BEHAVIOR; MEDIAL PREFRONTAL
CORTEX; AUTONOMIC NERVOUS-SYSTEM; HUMAN BRAIN STRUCTURE; MAJOR
DEPRESSION; PSYCHOLOGICAL STRESS; IMMUNE FUNCTION
AB Neuroscience was an integral part of psychosomatic medicine at its inception in the early 20th century. Since the mid-20th century, however, psychosomatic research has largely ignored the brain. The field of neuroscience has burgeoned in recent years largely because a variety of powerful new methods have become available. Many of these methods allow for the noninvasive study of the living human brain and thus are potentially available for integration into psychosomatic medicine research at this time. In this first paper we examine various methods available for human neuroscientific investigation and discuss their relative strengths and weaknesses. We next review some basic functional neuroanatomy involving structures that are increasingly being identified as relevant for psychosomatic processes. We then discuss, and provide examples of, flow the brain influences end organs through "information transfer systems," including the autonomic, neuroendocrine, and immune systems. The evidence currently available suggests that neuroscience holds great promise for advancing the goal of understanding the mechanisms by which psychosocial variables influence physical disease outcomes. An increased focus on such mechanistic research in psychosomatic medicine is needed to further its acceptance into the field of medicine.
C1 [Lane, Richard D.] Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA.
[Waldstein, Shari R.] Univ Maryland, Dept Psychol, Baltimore, MD 21201 USA.
[Waldstein, Shari R.] Baltimore VA Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA.
[Chesney, Margaret A.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Jennings, J. Richard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
VA Med Ctr, Behav Sci Labs, Oklahoma City, OK USA.
[Kozel, Peter J.] Natl Ctr Complementary & Alternat Med, Div Extramural Activ, NIH, Bethesda, MD USA.
[Rose, Robert M.] Mind Brain Body & Hlth Initiat, Galveston, TX USA.
[Drossman, Douglas A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Schneiderman, Neil] Univ Miami, Dept Psychol, Miami, FL USA.
[Thayer, Julian F.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
Univ Heidelberg, Mannheim Inst Publ Hlth, Heidelberg, Germany.
[Cameron, Oliver G.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Lane, RD (reprint author), Univ Arizona, Dept Psychiat, POB 245002, Tucson, AZ 85724 USA.
EM lane@email.arizona.edu
NR 192
TC 42
Z9 44
U1 5
U2 27
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD FEB-MAR
PY 2009
VL 71
IS 2
BP 117
EP 134
DI 10.1097/PSY.0b013e31819783be
PG 18
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 411NT
UT WOS:000263657000001
PM 19196808
ER
PT J
AU Arora, N
AF Arora, Neeraj K.
TI Importance of patient-centered care in enhancing patient well-being: a
cancer survivor's perspective
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Patient-centered care; Cancer; Patient experiences; Patient perspective;
Quality of care; Patient-physician communication; Cancer survivorship;
Well-being; Health-related quality of life
ID UNITED-STATES; QUALITY
AB In this narrative article, the author, a long-term cancer survivor, reflects on his personal interactions with the healthcare system over a period of 14 years in order to highlight the importance of delivering patient-centered care. He makes a case for why quality of care assessments are incomplete if they focus on clinical indicators of quality alone and exclude systematic assessment of the patient-centered aspects of care from the patient's perspective. The important role played by patient-centered care in reducing patient suffering and enhancing well-being is underscored in this commentary.
C1 NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Arora, N (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344,Execut Plaza N 4005, Bethesda, MD 20892 USA.
EM aroran@mail.nih.gov
NR 5
TC 21
Z9 21
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD FEB
PY 2009
VL 18
IS 1
BP 1
EP 4
DI 10.1007/s11136-008-9415-5
PG 4
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 402PM
UT WOS:000263025600001
PM 19005778
ER
PT J
AU Morgan, NY
Kramer-Marek, G
Smith, PD
Camphausen, K
Capala, J
AF Morgan, Nicole Y.
Kramer-Marek, Gabriela
Smith, Paul D.
Camphausen, Kevin
Capala, Jacek
TI Nanoscintillator Conjugates as Photodynamic Therapy-Based
Radiosensitizers: Calculation of Required Physical Parameters
SO RADIATION RESEARCH
LA English
DT Article
ID SINGLET OXYGEN LUMINESCENCE; GOLD NANOPARTICLES; IN-VITRO; MAGNETITE
NANOPARTICLES; INTRACELLULAR UPTAKE; CANCER-TREATMENT; QUANTUM YIELDS;
MLL CELLS; AGENTS; RADIATION
AB Morgan, N. Y., Kramer-Marek, G., Smith, P. D., Camphausen, K. and Capala, J. Nanoscintillator Conjugates as Photodynamic Therapy-Based Radiosensitizers: Calculation of Required Physical Parameters. Radiat. Res. 171, 236-244 (2009).
The recent demonstration of nanoscale scintillators has led to interest in the combination of radiation and photodynamic therapy. In this model, scintillating nanoparticles conjugated to photosensitizers and molecular targeting agents would enhance the targeting and improve the efficacy of radiotherapy and extend the application of photodynamic therapy to deeply seated tumors. In this study, we calculated the physical parameters required for these nanoparticle conjugates to deliver cytotoxic levels of singlet oxygen at therapeutic radiation doses, drawing on the published literature from several disparate fields. Although uncertainties remain, it appears that the light yield of the nanoscintillators, the efficiency of energy transfer to the photosensitizers, and the cellular uptake of the nanoparticles all need to be fairly well optimized to observe a cytotoxic effect. Even so, the efficacy of the combination therapy will likely be restricted to X-ray energies below 300 keV, which limits the application to brachytherapy. (C) 2009 by Radiation Research Society
C1 [Morgan, Nicole Y.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Kramer-Marek, Gabriela; Camphausen, Kevin; Capala, Jacek] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kramer-Marek, Gabriela] Univ Silesia, A Chelkowski Inst Phys, PL-40007 Katowice, Poland.
RP Morgan, NY (reprint author), NIBIB, Lab Bioengn & Phys Sci, NIH, Bldg 13,Room 3N18, Bethesda, MD 20892 USA.
EM morgann@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; National
Institute of Biomedical Imaging and Bioengineering
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and National
Institute of Biomedical Imaging and Bioengineering. The authors thank
Murali Cherukuri and Wei Chen for helpful discussions.
NR 34
TC 26
Z9 26
U1 2
U2 20
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 FEB
PY 2009
VL 171
IS 2
BP 236
EP 244
DI 10.1667/RR1470.1
PG 9
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 402PB
UT WOS:000263024500012
PM 19267550
ER
PT J
AU Perez-Rodriguez, J
Lai, S
Ehst, BD
Fine, DM
Bluemke, DA
AF Perez-Rodriguez, Javier
Lai, Shenghan
Ehst, Benjamin D.
Fine, Derek M.
Bluemke, David A.
TI Nephrogenic Systemic Fibrosis: Incidence, Associations, and Effect of
Risk Factor Assessment-Report of 33 Cases
SO RADIOLOGY
LA English
DT Article
ID RENAL-INSUFFICIENCY; PERCUTANEOUS TREATMENT; GADOLINIUM; DERMOPATHY;
ANGIOGRAPHY; CONTRAST; INVOLVEMENT; TISSUE
AB Purpose: To describe the presentation and clinical course of patients with nephrogenic systemic fibrosis (NSF) at a large acute-care hospital, to evaluate the overall incidence of NSF, and to assess the effect of a hospital-wide policy regarding gadolinium-based contrast agent (GBCA) use on NSF incidence.
Materials and Methods: A review of all cases of NSF observed at an institution from 2003 to 2008 was conducted. This HIPAA-compliant study was approved by the institutional review board. The informed consent requirement was waived. Demographics, medical history, and associated conditions were recorded. Radiologic procedures were evaluated if they were performed within 1 year prior to NSF onset. GBCA use was assessed by checking the electronic database for each procedure. The incidence of NSF was compared before and after implementation of an institutional policy designed to assess risk of NSF prior to GBCA use.
Results: All 33 patients with NSF (mean age, 49 years; age range, 15-78 years) had advanced renal failure (estimated glomerular filtration rate < 15 mL/min/1.73 m(2)) when the GBCA was injected. Twenty-six patients had severe chronic or end-stage renal disease, and seven had acute renal failure. The mean interval between contrast material injection and NSF onset was 29 days +/- 25 (standard deviation) (range, 4-112 days). The overall incidence of NSF was 36.5 cases per 100 000 gadolinium-enhanced magnetic resonance (MR) examinations between 2003 and 2006 and four cases per 100 000 gadolinium-enhanced MR examinations between 2007 and 2008 after screening for NSF risk was instituted (Fisher exact test, P = .001). Five patients developed NSF in the peritransplant period, and four underwent a catheter-based radiographic procedure with administration of a GBCA.
Conclusion: Common associations of GBCA MR imaging and NSF were acute and severe chronic renal failure and liver or renal transplantation. Screening procedures performed before MR imaging to determine which patients were at risk of developing NSF appear to reduce the incidence of this complication and further support the belief that NSF is associated with GBCA administration. (C) RSNA, 2009
C1 [Perez-Rodriguez, Javier; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Lai, Shenghan] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Fine, Derek M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21287 USA.
[Ehst, Benjamin D.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA.
RP Bluemke, DA (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Room 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
NR 25
TC 113
Z9 115
U1 0
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2009
VL 250
IS 2
BP 371
EP 377
DI 10.1148/radiol.2502080498
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 439QT
UT WOS:000265642800009
PM 19188312
ER
PT J
AU Abbatecola, AM
Cherubini, A
Guralnik, JM
Lacueva, CA
Ruggiero, C
Maggio, M
Bandinelli, S
Paolisso, G
Ferrucci, L
AF Abbatecola, Angela M.
Cherubini, Antonio
Guralnik, Jack M.
Lacueva, Cristina Andres
Ruggiero, Carmelinda
Maggio, Marcello
Bandinelli, Stefania
Paolisso, Giuseppe
Ferrucci, Luigi
TI Plasma Polyunsaturated Fatty Acids and Age-Related Physical Performance
Decline
SO REJUVENATION RESEARCH
LA English
DT Article
ID OLDER PERSONS; INFLAMMATORY MARKERS; PANCREATIC-CANCER; SKELETAL-MUSCLE;
HEALTH; N-3; DISABILITY; INCHIANTI; DISEASE; QUESTIONNAIRE
AB Due to supporting evidence that dietary patterns may have a significant role in the maintenance of good physical performance with aging, we tested whether plasma fatty acids, saturated fatty acids (SFA), and polyunsaturated (PUFA) fatty acids are cross-sectionally associated with different physical performance and predict changes in physical performance over a 3-year period. Data were from the InCHIANTI study, a population-based study of older Italians. Plasma fatty acids were measured at enrollment (1998-2000), and outcome variables, Summary Physical Performance Battery (SPPB), and time to walk 7 meters (m) were measured at enrollment and after 3 years (2001-2004). At enrollment, 330 participants had significantly impaired lower extremity performance (defined as a SPPB score <= 9). Adjusting for age, participants with a SPPB score >9 had higher levels of total PUFA, n-3 PUFA, and n-6 PUFA, while significantly lower levels of SFA than those with a SPPB score <9. Baseline SPPB scores were also associated with n-3 PUFA (beta = 0.148, p = 0.031), whereas the 7-m walk time was associated with total PUFA (beta = -0.068, p = 0.008), after adjusting for potential confounders. Of the 884 participants with a SPPB score >9 at baseline, 114 (12.9%) developed impaired lower extremity performance (SPPB <= 9). In fully adjusted logistic models, baseline n-3 PUFA levels were inversely related to the risk of developing a decline in SPPB to >9 (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.08-0.53), while the n-6/n-3 ratio was associated with a higher risk of SPPB decline to <= 9 (OR = 5.23; 95% CI = 2.02-13.51). In multivariate regression models, the n-6/n-3 ratio was associated with a longer time to walk 7 m (beta = 0.396, p = 0.037). n-3 PUFA plasma levels, which most likely reflect dietary intake, seem to protect against accelerated decline of physical performance. A higher n-6/n-3 ratio was associated with higher risk of developing poor physical performance and slower walking speed.
C1 [Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 4, I-80138 Naples, Italy.
[Cherubini, Antonio; Ruggiero, Carmelinda] Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriatr, Perugia, Italy.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Lacueva, Cristina Andres] Univ Barcelona, CeRTA, Dept Nutr & Food Sci, E-08007 Barcelona, Spain.
[Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Paolisso, G (reprint author), Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 4, Piazza Miraglia 2, I-80138 Naples, Italy.
EM giuseppe.paolisso@unina2.it
RI Andres-Lacueva, Cristina/J-3377-2012;
OI Andres-Lacueva, Cristina/0000-0002-8494-4978; Paolisso,
Giuseppe/0000-0002-2137-455X; Cherubini, Antonio/0000-0003-0261-9897
FU Italian Ministry of Health [ICS 110.1/RS97.71]; U. S. National Institute
on Aging [N01-AG-916413, N01-AG-821336]; U. S. National Institute on
Aging, National Institutes of Health, Baltimore, MD [263 MD 9164 13, 263
MD 821336]
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health, and in part by the U.
S. National Institute on Aging (contracts N01-AG-916413 and
N01-AG-821336), and by the Intramural Research Program of the U. S.
National Institute on Aging, National Institutes of Health, Baltimore,
MD (contracts 263 MD 9164 13 and 263 MD 821336). None of the sponsoring
institutions interfered with the collection, analysis, presentation, or
interpretation of the data reported here. All authors had full access to
all of the data in the study, and coauthors, Dr. Abbatecola, Dr.
Cherubini, Prof. Paolisso, and Dr. Ferrucci designed study protocol and
actively participated in writing the manuscript. Co-authors, Dr.
Guralnik, Dr. Lacueva, Dr. Ruggiero, Dr. Bandinelli, and Dr. Maggio
participated in study protocol design.
NR 33
TC 19
Z9 19
U1 0
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
J9 REJUV RES
JI Rejuv. Res.
PD FEB
PY 2009
VL 12
IS 1
BP 25
EP 32
DI 10.1089/rej.2008.0799
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 419CX
UT WOS:000264197800005
PM 19196012
ER
PT J
AU Reines, B
Cheng, LI
Matzinger, P
AF Reines, Brandon
Cheng, Lily I.
Matzinger, Polly
TI Unexpected Regeneration in Middle-Aged Mice
SO REJUVENATION RESEARCH
LA English
DT Article
ID EAR; STRAINS; TISSUE; MODEL
AB Complete regeneration of damaged extremities, including both the epithelium and the underlying tissues, is thought to occur mainly in embryos, fetuses, and juvenile mammals, but only very rarely in adult mammals. Surprisingly, we found that common strains of mice are able to regenerate all of the tissues necessary to completely fill experimentally punched ear holes, but only if punched at middle age. Although young postweaning mice regrew the epithelium without typical pre-scar granulation tissue, they showed only minimal regeneration of connective tissues. In contrast, mice punched at 5-11 months of age showed true amphibian-like blastema formation and regrowth of cartilage, fat, and dermis, with blood vessels, sebaceous glands, hair follicles, and, in black mice, melanocytes. These data suggest that at least partial appendage regeneration may be more common in adult mammals than previously thought and call into question the common view that regenerative ability is lost with age. The data suggest that the age at which various inbred mouse strains become capable of epimorphic regeneration may be correlated with adult body weight.
C1 [Reines, Brandon; Matzinger, Polly] NIAID, Ghost Lab, T Cell Tolerance & Memory Sect, Lab Cellular & Mol Immunol,NIH, Bethesda, MD 20892 USA.
[Cheng, Lily I.] NIAID, Vet Pathol Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Reines, B (reprint author), 4 Ctr Dr,MSC 111, Bethesda, MD 20892 USA.
EM BReines@niaid.nih.gov
FU NIAID, NIH
FX We would like to thank the following people for invaluable help,
including: pathologists Georgina Miller, Victoria Hoffman, and Jerry
Ward; medical illustrator Ethan Tyler; microscopist Owen Schwartz; data
analyst Maxwell Behrens; tool designers Jimmie Powell, Howard Metger,
and Frank Sharpnack; and all the members of the Ghost lab. Special
thanks to Xinmin Li for supplying a color version of an Excel graph
containing hole closure data from his 2001 Heredity paper for us to
reanalyze. We would also like to thank Ron Schwartz, Phil Murphy, and
Richard Hodes for suggestions on the manuscript. Last, but not least, we
thank to Victor Barcelona and Mary Kuta for software guidance. This work
was entirely supported by the intramural program of the NIAID, NIH.
NR 23
TC 5
Z9 5
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
J9 REJUV RES
JI Rejuv. Res.
PD FEB
PY 2009
VL 12
IS 1
BP 45
EP 51
DI 10.1089/rej.2008.0792
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 419CX
UT WOS:000264197800007
PM 19226206
ER
PT J
AU Perez, V
Sierra, F
AF Perez, Viviana
Sierra, Felipe
TI Biology of aging
SO REVISTA MEDICA DE CHILE
LA Spanish
DT Article
DE Aging; Genes; Stem cells
ID LIFE-SPAN; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; OXIDATIVE
STRESS; CELLULAR SENESCENCE; SIGNALING PATHWAY; TUMOR SUPPRESSION;
HUMAN-DISEASE; AGE-1 GENE; C-ELEGANS
AB The study of biological aging has seen a spectacularly fast progress in the last decade. Besides a better understanding and comprehension of physiological aspects, an important advance has been the identification of at least a hundred different genes which control the process of aging. Their mechanism of action falls within the expectations from a handful of theories which attempt to provide a global explanation of the phenomenon of aging, including free radicals, cell senescence and loss of regenerative capacity through the activation of stem cells. In this review we will concentrate in these biological aspects, with a special emphasis on animal models used to study both the genetics and physiology of aging as well as experimental approaches to test the the aforementioned theories. It should be emphasized that, while the emphasis is in purely biological aspects of the process, the fast pace of aging of the world's population, including Chile, needs a rapid advance also in our understanding of its social and economic implications (Rev Med Chile 2009; 137: 296-302).
C1 [Sierra, Felipe] NIA, NIH, Bethesda, MD 20892 USA.
[Perez, Viviana] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
RP Sierra, F (reprint author), NIA, NIH, 7201 Wisconsin Ave,Suite 2C231, Bethesda, MD 20892 USA.
EM sierrag@nia.nih.gov
NR 61
TC 1
Z9 1
U1 2
U2 5
PU SOC MEDICA SANTIAGO
PI SANTIAGO 9
PA BERNARDA MORIN 488 PROVIDENCIA, CASILLA 168 CORREO 55, SANTIAGO 9,
00000, CHILE
SN 0034-9887
EI 0717-6163
J9 REV MED CHILE
JI Rev. Medica Chile
PD FEB
PY 2009
VL 137
IS 2
BP 296
EP 302
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 454ZL
UT WOS:000266723800017
PM 19543655
ER
PT J
AU Harris-Love, MO
Shrader, JA
Koziol, D
Pahlajani, N
Jain, M
Smith, M
Cintas, HL
McGarvey, CL
James-Newton, L
Pokrovnichka, A
Moini, B
Cabalar, I
Lovell, DJ
Wesley, R
Plotz, PH
Miller, FW
Hicks, JE
Rider, LG
AF Harris-Love, M. O.
Shrader, J. A.
Koziol, D.
Pahlajani, N.
Jain, M.
Smith, M.
Cintas, H. L.
McGarvey, C. L.
James-Newton, L.
Pokrovnichka, A.
Moini, B.
Cabalar, I.
Lovell, D. J.
Wesley, R.
Plotz, P. H.
Miller, F. W.
Hicks, J. E.
Rider, L. G.
TI Distribution and severity of weakness among patients with polymyositis,
dermatomyositis and juvenile dermatomyositis
SO RHEUMATOLOGY
LA English
DT Article
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; HEALTH ASSESSMENT QUESTIONNAIRE;
VALIDATED DISEASE-ACTIVITY; LONG-TERM SURVIVAL; QUALITY-OF-LIFE; MUSCLE
STRENGTH; DAMAGE INDEXES; ADULT; MYOSITIS; PROGNOSIS
AB Objective. To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis.
Methods. Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses.
Results. A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically.
Conclusions. Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.
C1 [Harris-Love, M. O.; James-Newton, L.; Miller, F. W.; Rider, L. G.] NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA.
[Harris-Love, M. O.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
[Pahlajani, N.; Pokrovnichka, A.; Moini, B.; Cabalar, I.; Plotz, P. H.] NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lovell, D. J.] Cincinnati Childrens Hosp, Med Ctr, Div Rheumatol, Cincinnati, OH USA.
RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
RI Harris-Love, Michael/J-1359-2014;
OI Harris-Love, Michael/0000-0002-1842-3269; Rider,
Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences; National Institute
of Arthritis and Musculoskeletal and Skin Diseases; Rehabilitation
Medicine Department; NIH Clinical Center
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences, National Institute of Arthritis and Musculoskeletal and
Skin Diseases, Rehabilitation Medicine Department and the NIH Clinical
Center.
NR 45
TC 45
Z9 47
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD FEB
PY 2009
VL 48
IS 2
BP 134
EP 139
DI 10.1093/rheumatology/ken441
PG 6
WC Rheumatology
SC Rheumatology
GA 395IT
UT WOS:000262518500009
PM 19074186
ER
PT J
AU Rangel-Santos, A
Wakim, VL
Jacob, CM
Pastorino, AC
Cunha, JM
Collanieri, AC
Niemela, JE
Grumach, AS
Duarte, AJS
Moraes-Vasconcelos, D
Oliveira, JB
AF Rangel-Santos, A.
Wakim, V. L.
Jacob, C. M.
Pastorino, A. C.
Cunha, J. M.
Collanieri, A. C.
Niemela, J. E.
Grumach, A. S.
Duarte, A. J. S.
Moraes-Vasconcelos, D.
Oliveira, J. B.
TI Molecular Characterization of Patients with X-linked Hyper-IgM Syndrome:
Description of Two Novel CD40L Mutations
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LIGAND; IMMUNODEFICIENCY; PROTEINS
AB Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.
C1 [Oliveira, J. B.] NIH, Immunl Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Rangel-Santos, A.; Collanieri, A. C.; Grumach, A. S.; Duarte, A. J. S.; Moraes-Vasconcelos, D.; Oliveira, J. B.] Univ Sao Paulo, Fac Med, Lab Med Invest Unit 56, Dept Dermatol,LIM 56, Sao Paulo, Brazil.
[Wakim, V. L.] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil.
[Jacob, C. M.; Pastorino, A. C.] Univ Sao Paulo, Fac Med, Allergy & Immunol Serv, Dept Pediat, Sao Paulo, Brazil.
RP Oliveira, JB (reprint author), NIH, Immunl Serv, Dept Lab Med, Ctr Clin, EUA Bldg 10,Room 2C410,10 Ctr Dr, Bethesda, MD 20892 USA.
EM oliveirajb@cc.nih.gov
RI Duarte, Alberto/D-4382-2012; Moraes-Vasconcelos, Dewton/G-2209-2012;
Cunha, Jose Marcos/J-7030-2014; Rangel Santos, Andreia/E-9985-2016;
OI Cunha, Jose Marcos/0000-0003-3264-0929; Niemela,
Julie/0000-0003-4197-3792; Oliveira, Joao/0000-0001-9388-8173; Grumach,
Anete/0000-0002-9803-0309
NR 21
TC 5
Z9 6
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-9475
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD FEB
PY 2009
VL 69
IS 2
BP 169
EP 173
DI 10.1111/j.1365-3083.2008.02198.x
PG 5
WC Immunology
SC Immunology
GA 397XA
UT WOS:000262694400011
PM 19170966
ER
PT J
AU Maurex, L
Zaboli, G
Wiens, S
Asberg, M
Leopardi, R
Ohman, A
AF Maurex, Liselotte
Zaboli, Ghazal
Wiens, Stefan
Asberg, Marie
Leopardi, Rosario
Ohman, Arne
TI Emotionally controlled decision-making and a gene variant related to
serotonin synthesis in women with borderline personality disorder
SO SCANDINAVIAN JOURNAL OF PSYCHOLOGY
LA English
DT Article
DE Borderline personality disorder; tryptophan hydroxylase-1 gene;
serotonin; decision-making; Iowa Gambling Task
ID TRYPTOPHAN-HYDROXYLASE GENE; IOWA GAMBLING TASK; DSM-III-R;
SUICIDAL-BEHAVIOR; IMPULSIVITY; ASSOCIATION; DEFICITS; FAMILY; CORTEX
AB Maurex, L., Zaboli, G., Wiens, S., angstrom sberg, M., Leopardi, R. & ohman, A. (2008). Emotionally controlled decision-making and a gene variant related to serotonin synthesis in women with borderline personality disorder. Scandinavian Journal of Psychology, 50, 5-10.
The Iowa Gambling Task (IGT) was used to examine (i) social decision-making in women with borderline personality disorder (BPD), and (ii) the relationship between impaired decision-making and the tryptophan hydroxylase-1 (TPH-1) gene, involved in serotonin synthesis. Forty-two women with BPD and a history of suicide attempts were genotyped, and the frequency of a TPH-1 haplotype previously uniquely associated with BPD was calculated. The BPD group scored significantly lower than a control group in the IGT. Furthermore, the TPH-1 haplotype displayed a significantly higher frequency in BPD participants with impaired decision making, compared to BPD participants with normal scores. These findings suggest that impaired decision-making as determined by the IGT is a feature of BPD and may be (i) associated with serotonin dysfunction, and (ii) possibly relevant for suicidal behavior.
C1 [Maurex, Liselotte; Wiens, Stefan; Ohman, Arne] Karolinska Inst, Dept Clin Neurosci, Psychol Sect, S-17177 Stockholm, Sweden.
[Zaboli, Ghazal; Leopardi, Rosario] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17177 Stockholm, Sweden.
[Zaboli, Ghazal; Leopardi, Rosario] Karolinska Inst, Ctr Mol Med, S-17177 Stockholm, Sweden.
[Wiens, Stefan] Stockholm Univ, Dept Psychol, Stockholm, Sweden.
[Ohman, Arne] Ctr Adv Study Behav Sci, Stanford, CA 94305 USA.
[Ohman, Arne] Stockholm Brain Inst, Stockholm, Sweden.
[Ohman, Arne] Univ Florida, NIMH, Ctr Res Emot & Attent, Gainesville, FL 32611 USA.
[Asberg, Marie] Karolinska Inst, Dept Clin Sci, S-17177 Stockholm, Sweden.
RP Ohman, A (reprint author), Karolinska Inst, Dept Clin Neurosci, Psychol Sect, S-17177 Stockholm, Sweden.
EM Arne.Ohman@ki.se
NR 41
TC 23
Z9 26
U1 1
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0036-5564
J9 SCAND J PSYCHOL
JI Scand. J. Psychol.
PD FEB
PY 2009
VL 50
IS 1
BP 5
EP 10
DI 10.1111/j.1467-9450.2008.00689.x
PG 6
WC Psychology, Multidisciplinary
SC Psychology
GA 394XY
UT WOS:000262487700003
PM 18826425
ER
PT J
AU Lemelin, ET
Roux, AVD
Franklin, TG
Carnethon, M
Lutsey, PL
Ni, HY
O'Meara, E
Shrager, S
AF Lemelin, Emily T.
Roux, Ana V. Diez
Franklin, Tracy G.
Carnethon, Mercedes
Lutsey, Pamela L.
Ni, Hanyu
O'Meara, Ellen
Shrager, Sandi
TI Life-course socioeconomic positions and subclinical atherosclerosis in
the multi-ethnic study of atherosclerosis
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Socioeconomic position; Subclinical disease; Life-course; USA;
Neighborhood; Atherosclerosis; Ethnicity; Gender
ID CORONARY-HEART-DISEASE; INTIMA-MEDIA-THICKNESS; CARDIOVASCULAR-DISEASE;
CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; NEIGHBORHOOD
DEPRIVATION; HEALTH RESEARCH; SOCIAL-CLASS; RISK; WOMEN
AB A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in inaccurate estimates of the social patterning of subclinical disease. Using data from the US Multi-Ethnic Study of Atherosclerosis (MESA), we examined the relation between childhood SEP [CSEP] (father or caretaker's education), adulthood SEP [ASEP] (a summary score of income, education, and wealth), and 20-year average exposure to neighborhood poverty [NSEP] (residential addresses geocoded and linked to census data) and the prevalence of subclinical atherosclerosis, as assessed by common carotid intimal-medial thickness (IMT) in mid to late adulthood. Participants were 45-84 years of age at baseline and were sampled from six study sites in the United States. After adjustment for age, CSEP and ASEP were both inversely and independently associated with IMT in men. All three indicators CSEP, ASEP, and NSEP were inversely and independently associated with IMT in women. Associations were somewhat reduced after adjustment for cardiovascular risk factors, suggesting that these factors may play a mediating role. There was evidence of heterogeneity in effects of NSEP by gender, and in the effects of ASEP and NSEP by race/ethnicity. Our results contribute to the growing body of work that shows that SEP at multiple points in the life-course, and at the individual and neighborhood level, contributes to the development of atherosclerosis. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Lemelin, Emily T.; Roux, Ana V. Diez; Franklin, Tracy G.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48104 USA.
[Carnethon, Mercedes] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Ni, Hanyu] NHLBI, NIH, Bethesda, MD 20892 USA.
[O'Meara, Ellen] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Shrager, Sandi] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Washington, DC USA.
RP Lemelin, ET (reprint author), Univ Michigan, Dept Epidemiol, 1214 S Univ, Ann Arbor, MI 48104 USA.
EM elemelin@nshd.mrc.ac.uk; adiezrou@umich.edu; greentl@umich.edu;
carnethon@northwestern.edu; lutsey@epi.umn.edu; hn79e@nih.gov;
eomeara@u.washington.edu; sandis@u.washington.edu
FU NHLBI NIH HHS [N01-HC-95161, N01-HC-95163, N01-HC-95165, N01-HC-95169,
N01 HC048049, N01-HC-95159, N01-HC-95160, N01-HC-95162, N01-HC-95164,
R01-HL071759]
NR 58
TC 37
Z9 39
U1 1
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2009
VL 68
IS 3
BP 444
EP 451
DI 10.1016/j.socscimed.2008.10.038
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 408GX
UT WOS:000263424600008
PM 19081660
ER
PT J
AU Shaw, PA
Pepe, MS
Alonzo, TA
Etzioni, R
AF Shaw, Pamela A.
Pepe, Margaret S.
Alonzo, Todd A.
Etzioni, Ruth
TI Methods for Assessing Improvement in Specificity When a Biomarker is
Combined With a Standard Screening Test
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Diagnostic tests; Relative accuracy; ROC curve; Specificity; Study
design
AB Biomarkers that can be used in combination with established screening tests to reduce false positive rates are in considerable demand. In this article, we present methods for evaluating the diagnostic performance of combination tests that require positivity on a biomarker test in addition to a standard screening test. These methods rely on relative true-and false-positive rates to measure the loss in sensitivity and gain in specificity associated with the combination relative to the standard test. Inference about the relative rates follows from noting their interpretation as conditional probabilities. These methods are extended to evaluate combinations with continuous biomarker tests by introducing a new statistical entity, the relative receiver operating characteristic (rROC) curve. The rROC curve plots the relative true positive rate versus the relative false positive rate as the biomarker threshold for positivity varies. Inference can be made by applying existing ROC methodology. We illustrate the methods with two examples: a breast cancer biomarker study proposed by the Early Detection Research Network (EDRN) and a prostate cancer case-control study examining the ability of free prostate-specific antigen (PSA) to improve the specificity of the standard PSA test.
C1 [Shaw, Pamela A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Pepe, Margaret S.; Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Alonzo, Todd A.] Univ So Calif, Dept Biostat, Keck Sch Med, Arcadia, CA 91006 USA.
RP Shaw, PA (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shawpa@niaid.nih.gov; mspepe@u.washington.edu;
talonzo@childrensoncologygroup.org; retzioni@fhcrc.org
FU Intramural NIH HHS [Z99 AI999999]
NR 24
TC 5
Z9 5
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PD FEB
PY 2009
VL 1
IS 1
BP 18
EP 25
DI 10.1198/sbr.2009.0002
PG 8
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA V17ZI
UT WOS:000207974700003
PM 20054437
ER
PT J
AU Nambi, V
Hoogeveen, RC
Chambless, L
Hu, YJ
Bang, HJ
Coresh, J
Ni, HY
Boerwinkle, E
Mosley, T
Sharrett, R
Folsom, AR
Ballantyne, CM
AF Nambi, Vijay
Hoogeveen, Ron C.
Chambless, Lloyd
Hu, Yijuan
Bang, Heejung
Coresh, Josef
Ni, Hanyu
Boerwinkle, Eric
Mosley, Thomas
Sharrett, Richey
Folsom, Aaron R.
Ballantyne, Christie M.
TI Lipoprotein-Associated Phospholipase A(2) and High-Sensitivity
C-Reactive Protein Improve the Stratification of Ischemic Stroke Risk in
the Atherosclerosis Risk in Communities (ARIC) Study
SO STROKE
LA English
DT Article
DE CRP; Lp-PLA(2); risk; stroke
ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; PRIMARY PREVENTION; BLOOD
CHOLESTEROL; PREDICTIVE MODELS; EVENTS; COHORT; WOMEN; INFLAMMATION;
SIMVASTATIN
AB Background and Purpose-Inflammation plays a critical role in the development of vascular disease, and increased levels of the inflammatory biomarkers, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), and high-sensitivity C-reactive protein (hs-CRP) have been shown to be associated with an increased risk for ischemic stroke.
Methods-In a prospective case-cohort (n = 949) study in 12 762 apparently healthy, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study, we first examined whether Lp-PLA(2) and hs-CRP levels improved the area under the receiver operator characteristic curve (AUC) for 5-year ischemic stroke risk. We then examined how Lp-PLA(2) and hs-CRP levels altered classification of individuals into low-, intermediate-, or high-risk categories compared with traditional risk factors.
Results-In a model using traditional risk factors alone, the AUC adjusted for optimism was 0.732, whereas adding hs-CRP improved the AUC to 0.743, and adding Lp-PLA(2) significantly improved the AUC to 0.752. Addition of hs-CRP and Lp-PLA(2) together in the model improved the AUC to 0.761, and the addition of the interaction between Lp-PLA(2) and hs-CRP further significantly improved the AUC to 0.774. With the use of traditional risk factors to assess 5-year risk for ischemic stroke, 86% of participants were categorized as low risk (<2%); 11%, intermediate risk (2% to 5%); and 3%, high risk (>5%). The addition of hs-CRP, Lp-PLA(2), and their interaction to the model reclassified 4%, 39%, and 34% of the low-, intermediate- and high-risk categories, respectively.
Conclusion-Lp-PLA(2) and hs-CRP may be useful in individuals classified as intermediate risk for ischemic stroke by traditional risk factors. (Stroke. 2009; 40: 376-381.)
C1 [Nambi, Vijay; Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA.
[Nambi, Vijay; Hoogeveen, Ron C.; Ballantyne, Christie M.] Methodist DeBakey Heart Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA.
[Chambless, Lloyd; Hu, Yijuan] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Bang, Heejung] Cornell Univ, Weill Med Coll, Dept Publ Hlth, Div Biostat & Epidemiol, New York, NY 10021 USA.
[Coresh, Josef; Sharrett, Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Ni, Hanyu] NIH, Bethesda, MD 20892 USA.
[Boerwinkle, Eric] Univ Texas Houston Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Houston Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Mosley, Thomas] Univ Mississippi, Dept Med, Jackson, MS 39216 USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Ballantyne, CM (reprint author), Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, 6565 Fannin,MS STE-B-160 A-601, Houston, TX 77030 USA.
EM cmb@bcm.tmc.edu
FU NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022]; GlaxoSmithKline, Research
Triangle Park, NC
FX The National Heart, Lung, and Blood Institute (NHLBI) participated in
the design and conduct of the study, and the NHLBI Project Office
participated in the preparation and review of the manuscript. The
Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
and N01-HC-55022 from the (NHLBI, Bethesda, Md. This research was also
supported by an unrestricted research grant from GlaxoSmithKline,
Research Triangle Park, NC.
NR 45
TC 39
Z9 50
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2009
VL 40
IS 2
BP 376
EP 381
DI 10.1161/STROKEAHA.107.513259
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 399FD
UT WOS:000262784900007
PM 19095974
ER
PT J
AU Guo, SZ
Arai, K
Stins, MF
Chuang, DM
Lo, EH
AF Guo, Shuzhen
Arai, Ken
Stins, Monique F.
Chuang, De-Maw
Lo, Eng H.
TI Lithium Upregulates Vascular Endothelial Growth Factor in Brain
Endothelial Cells and Astrocytes
SO STROKE
LA English
DT Article
DE growth factor; neuroprotection; neurovascular unit; stroke recovery
ID GLYCOGEN-SYNTHASE KINASE-3; NEUROPROTECTION; VEGF; INHIBITION;
INDUCTION; SURVIVAL; NEURONS; MODEL
AB Background and Purpose-We recently reported that delayed lithium therapy can improve stroke recovery in rats by augmenting neurovascular remodeling. We tested the hypothesis that lithium can promote the expression of growth factors in brain endothelial cells and astrocytes.
Methods-Human brain microvascular endothelial cells and primary rat cortical astrocytes were exposed to lithium chloride in serum-free medium. We examined 2 representative growth factors: brain-derived neurotrophic factor and vascular endothelial growth factor (VEGF). Cell lysates were collected for Western blot analysis. Conditioned media was analyzed with enzyme-linked immunosorbent assay. SB-216763 and LY294002 were used to assess the roles of the glycogen synthase kinase-3 beta (GSK-3 beta) and PI3-K signaling in the lithium-induced responses.
Results-No consistent responses were observed for brain-derived neurotrophic factor. However, lithium (0.2 to 20 mmol/L) increased the phosphorylation of GSK-3 beta and promoted VEGF secretion in a concentration-dependent manner in both endothelial and astrocyte cells. For endothelial cells, the potent GSK-3 beta inhibitor SB-216763 upregulated VEGF, whereas inhibition of PI3-K with LY294002 suppressed lithium-induced responses in both phospho-GSK-3 beta and VEGF. In contrast, neither inhibition of GSK-3 beta nor inhibition of PI3-K had any detectable effects on VEGF levels in astrocytes.
Conclusions-Lithium promotes VEGF expression through PI3-K/GSK-3 beta-dependent and-independent pathways in brain endothelium and astrocytes, respectively. This growth factor signaling mechanism may contribute to lithium's reported ability to promote neurovascular remodeling after stroke. (Stroke. 2009;40:652-655.)
C1 [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, Bethesda, MD 20892 USA.
[Stins, Monique F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA.
RP Lo, EH (reprint author), MGH East 149-2401, Charlestown, MA 02129 USA.
EM Lo@helix.mgh.harvard.edu
FU American Heart Association Bugher; National Institutes of Health
[R01-NS48422, R01-NS53560, P50-NS10828, P01-NS55104]
FX Supported in part by an American Heart Association Bugher award and
National Institutes of Health grants R01-NS48422, R01-NS53560,
P50-NS10828, and P01-NS55104.
NR 18
TC 36
Z9 39
U1 1
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 FEB
PY 2009
VL 40
IS 2
BP 652
EP 655
DI 10.1161/STROKEAHA.108.524504
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 399FD
UT WOS:000262784900050
PM 18974377
ER
PT J
AU Gray, TR
Kelly, T
LaGasse, LL
Smith, LM
Derauf, C
Haning, W
Grant, P
Shah, R
Arria, A
Strauss, A
Lester, BM
Huestis, MA
AF Gray, Teresa R.
Kelly, Tamsin
LaGasse, Linda L.
Smith, Lynne M.
Derauf, Chris
Haning, William
Grant, Penny
Shah, Rizwan
Arria, Amelia
Strauss, Arthur
Lester, Barry M.
Huestis, Marilyn A.
TI Novel Biomarkers of Prenatal Methamphetamine Exposure in Human Meconium
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE methamphetamine; meconium; in utero
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; LIFE-STYLE; INFANT DEVELOPMENT;
MASS-SPECTROMETRY; MAJOR METABOLITES; URINARY-EXCRETION; HAIR ANALYSIS;
DRUG-USE; AMPHETAMINE; PREGNANCY
AB Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine (MAMP) and amphetamine (AMP) have previously been observed in meconium of MAMP-exposed neonates; the presence of other metabolites has not been investigated. Detection of such analytes may lead to more sensitive identification and thus improved medical treatment of affected infants. Forty-three MAMP-positive meconium specimens were analyzed for newly identified MAMP biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to MAMP adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetaniine and MAMP prenatal exposure, 3,4-methylenedioxymethamphetamine, its metabolites, and related sympathomimetic amines were assayed. MAMP AM-P, and unconjugated p-hydroxyrnethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetarnine and norephedrine also were identified. It is possible that one of these additional analytes could be important for predicting toxicity or maternal or neonatal outcome measures in fetuses exposed to MAMP at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than MAMP and AMP in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of MAMP-exposed neonates. Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to MAMP
C1 [Gray, Teresa R.; Kelly, Tamsin; Huestis, Marilyn A.] NIDA, Intramural Res Program, Natl Inst Hlth, Baltimore, MD USA.
[Kelly, Tamsin] Curtin Univ Technol, Dept Appl Chem, Perth, WA, Australia.
[LaGasse, Linda L.; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Study Children Risk, Brown Ctr, Providence, RI 02912 USA.
[LaGasse, Linda L.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Dept Pediat, Torrance, CA 90509 USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Torrance, CA USA.
[Derauf, Chris] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA.
[Haning, William] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA.
[Grant, Penny] Univ Oklahoma, Dept Pediat, Tulsa, OK USA.
[Shah, Rizwan] Blank Childrens Hosp, Dept Pediat, Des Moines, IA USA.
[Arria, Amelia] Univ Maryland, Ctr Subst Abuse Res, College Pk, MD 20742 USA.
[Strauss, Arthur] Long Beach Mem Med Ctr, Dept Pediat, Long Beach, CA USA.
RP Huestis, MA (reprint author), 251 Bayview Blvd,Suite 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI Kelly, Tamsin/A-2456-2009;
OI Kelly, Tamsin/0000-0002-8946-9686; Arria, Amelia/0000-0002-6360-9265
FU Intramural Research Program, National Institutes of Health; National
Institute on Drug Abuse
FX This research was funded by the Intramural Research Program, National
Institutes of Health, National Institute on Drug Abuse. The authors
thank the US Drug Testing Laboratory for donating authentic
MAMP-positive meconium specimens.
NR 40
TC 4
Z9 4
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD FEB
PY 2009
VL 31
IS 1
BP 70
EP 75
PG 6
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 400OX
UT WOS:000262879000008
PM 19125148
ER
PT J
AU Bueno, DF
Kerkis, I
Costa, AM
Martins, MT
Kobayashi, GS
Zucconi, E
Fanganiello, RD
Salles, FT
Almeida, AB
do Amaral, CER
Alonso, N
Passos-Bueno, MR
AF Bueno, Daniela Franco
Kerkis, Irina
Costa, Andre Mendonca
Martins, Marilia T.
Kobayashi, Gerson Shigeru
Zucconi, Eder
Fanganiello, Roberto Dalto
Salles, Felipe T.
Almeida, Ana Beatriz
Raposo do Amaral, Cassio Eduardo
Alonso, Nivaldo
Passos-Bueno, Maria Rita
TI New Source of Muscle-Derived Stem Cells with Potential for Alveolar Bone
Reconstruction in Cleft Lip and/or Palate Patients
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID SKELETAL-MUSCLE; TISSUE; GRAFTS; OSTEOPLASTY; DEFECTS; REPAIR; ADULT
AB Cleft lip and palate (CLP), one of the most frequent congenital malformations, affects the alveolar bone in the great majority of the cases, and the reconstruction of this defect still represents a challenge in the rehabilitation of these patients. One of the current most promising strategy to achieve this goal is the use of bone marrow stem cells (BMSC); however, isolation of BMSC or iliac bone, which is still the mostly used graft in the surgical repair of these patients, confers site morbidity to the donor. Therefore, in order to identify a new alternative source of stem cells with osteogenic potential without conferring morbidity to the donor, we have used orbicular oris muscle (OOM) fragments, which are regularly discarded during surgery repair (cheiloplasty) of CLP patients. We obtained cells from OOM fragments of four unrelated CLP patients (CLPMDSC) using previously described preplating technique. These cells, through flow cytometry analysis, were mainly positively marked for five mesenchymal stem cell antigens (CD29, CD90, CD105, SH3, and SH4), while negative for hematopoietic cell markers, CD14, CD34, CD45, and CD117, and for endothelial cell marker, CD31. After induction under appropriate cell culture conditions, these cells were capable to undergo chondrogenic, adipogenic, osteogenic, and skeletal muscle cell differentiation, as evidenced by immunohistochemistry. We also demonstrated that these cells together with a collagen membrane lead to bone tissue reconstruction in a critical-size cranial defects previously induced in non-immunocompromised rats. The presence of human DNA in the new bone was confirmed by PCR with human-specific primers and immunohistochemistry with human nuclei antibodies. In conclusion, we showed that cells from OOM have phenotypic and behavior characteristics similar to other adult stem cells, both in vitro and in vivo. Our findings suggest that these cells represent a promising source of stem cells for alveolar bone grafting treatment, particularly in young CLP patients.
C1 [Bueno, Daniela Franco] Univ Sao Paulo, Inst Biosci, Ctr Human Genome, BR-05508090 Sao Paulo, Brazil.
[Kerkis, Irina] Butantan Inst, Dept Genet, Sao Paulo, Brazil.
[Costa, Andre Mendonca; Alonso, Nivaldo] Univ Sao Paulo, Fac Med, Dept Plast Surg, BR-05508090 Sao Paulo, Brazil.
[Costa, Andre Mendonca] State Univ Hlth Sci Alagoas, Dept Plast Surg, Alagoas, Brazil.
[Martins, Marilia T.] Univ Sao Paulo, Dept Oral Pathol, BR-05508090 Sao Paulo, Brazil.
[Salles, Felipe T.; Almeida, Ana Beatriz] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Raposo do Amaral, Cassio Eduardo] SOBRAPAR, Campinas, SP, Brazil.
RP Bueno, DF (reprint author), Univ Sao Paulo, Inst Biosci, Ctr Human Genome, Rua Matao 277, BR-05508090 Sao Paulo, Brazil.
EM passos@ib.usp.br
RI Salles, Felipe/H-7544-2013; Celulas tronco, Inct/I-1921-2013; Cetgen,
Inct/I-2412-2013; Trierveiler, Marilia/N-7359-2015; Raposo Amaral,
Cassio Eduardo/D-1397-2013; Passos-Bueno, Maria Rita/I-6796-2016;
Kobayashi, Gerson/H-4017-2013;
OI Trierveiler, Marilia/0000-0002-8517-2105; Raposo Amaral, Cassio
Eduardo/0000-0001-6201-0827; Passos-Bueno, Maria
Rita/0000-0002-9248-3008; Kobayashi, Gerson/0000-0002-6520-5774;
Zucconi, Eder/0000-0002-5904-4564; Bueno, Daniela F/0000-0001-5932-6134
FU FAPESP/CEPID; CNPq
FX The authors would like to express their gratitude to Professor Cassio
Raposo do Amaral (1943-2005) for his incentive and fruitful ideas on new
insights in rehabilitating craniofacial malformation; Professor Mayana
Zatz for her incentive on stem cells research, Dr. Bechara Kachar, M.
D., who allowed the use of his facility at NIH; Dr. Mariz Vainzof for
the muscle antibodies; Mrs. Constancia Urbani for secretarial
assistance, and the following colleagues for assistance: Carlos
Maranduba, Ph. D.; Alexandre Kerkis, Ph. D.; Fernanda S. Jehee, Ph. D.;
Rogerio Castilho, Ph. D.; Marta Canovas, Erika Yeh, and Natassia Vieira.
FAPESP/CEPID and CNPq sponsored this study.
NR 36
TC 28
Z9 32
U1 1
U2 10
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD FEB
PY 2009
VL 15
IS 2
BP 427
EP 435
DI 10.1089/ten.tea.2007.0417
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 403BR
UT WOS:000263057300022
PM 18816169
ER
PT J
AU Kaczmarek, M
Cachau, RE
Topol, IA
Kasprzak, KS
Ghio, A
Salnikow, K
AF Kaczmarek, Monika
Cachau, Raul E.
Topol, Igor A.
Kasprzak, Kazimierz S.
Ghio, Andy
Salnikow, Konstantin
TI Metal Ions-Stimulated Iron Oxidation in Hydroxylases Facilitates
Stabilization of HIF-1 alpha Protein
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR; PROLYL 4-HYDROXYLASE ACTIVITY; SOLUBLE
TRANSITION-METALS; AIRWAY EPITHELIAL-CELLS; L-ASCORBIC-ACID; OIL
FLY-ASH; PROLINE HYDROXYLATION; CRYSTAL-STRUCTURE; A549 CELLS; HIF-ALPHA
AB The exposure of cells to several metal ions stabilizes HIF-1 alpha protein. However, the molecular mechanisms are not completely understood. They may involve inhibition of hydroxylation by either substitution of iron by metal ions or by iron oxidation in the hydroxylases. Here we provide evidence supporting the latter mechanism. We show that HIF-1 alpha stabilization in human lung epithelial cells occurred following exposure to various metal and metalloid ions, including those that cannot substitute for iron in the hydroxylases. In each case addition of the reducing agent ascorbic acid (AA)* abolished HIF-1 alpha protein stabilization. To better understand the role of iron oxidation in hydroxylase inhibition and to define the role of AA in the enzyme recovery we applied molecular modeling techniques. Our results indicate that the energy required for iron substitution by Ni(II) in the enzyme is high and unlikely to be achieved in a biological system. Additionally, computer modeling allowed us to identify a tridentate coordination of AA with the enzyme-bound iron, which explains the specific demand for AA as the iron reductant. Thus, the stabilization of HIF-1 alpha by numerous metal ions that cannot substitute for iron in the enzyme, the alleviation of this effect by AA, and our computer modeling data support the hypothesis of iron oxidation in the hydroxylases following exposure to metal ions.
C1 [Kaczmarek, Monika; Kasprzak, Kazimierz S.; Salnikow, Konstantin] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Cachau, Raul E.; Topol, Igor A.] NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Adv Technol Program, Frederick, MD 21701 USA.
[Ghio, Andy] US EPA, Res Triangle Pk, NC 27711 USA.
RP Salnikow, K (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205 E, Frederick, MD 21701 USA.
EM salnikok@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; National Institutes of Health [N01-CO-12400]
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, and National Cancer Institute, National
Institutes of Health, under contract no. (N01-CO-12400).
NR 50
TC 17
Z9 18
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 FEB
PY 2009
VL 107
IS 2
BP 394
EP 403
DI 10.1093/toxsci/kfn251
PG 10
WC Toxicology
SC Toxicology
GA 398HK
UT WOS:000262723000010
PM 19074761
ER
PT J
AU Jiang, T
Bell, DR
Clode, S
Fan, MQ
Fernandes, A
Foster, PMD
Loizou, G
MacNicoll, A
Miller, BG
Rose, M
Tran, L
White, S
AF Jiang, Tao
Bell, David R.
Clode, Sally
Fan, Ming Qi
Fernandes, Alwyn
Foster, Paul M. D.
Loizou, George
MacNicoll, Alan
Miller, Brian G.
Rose, Martin
Tran, Lang
White, Shaun
TI A Truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) Rat
Does Not Affect the Developmental Toxicity of TCDD
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
ID MALE WISTAR(HAN) RAT; AH-RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
TCDD; MATERNAL EXPOSURE; RESISTANT RAT; MICE LACKING; IN-UTERO; BINDING;
HYDROXYLASE; EXPRESSION
AB The aryl hydrocarbon receptor (AhR) is required for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and so the AhR of CRL:WI and CRL:WI(Han) rats was characterized. Western blot showed AhR proteins of similar to 110 and similar to 97 kDa in individual rats from both strains. The AhR cDNA from a CRL:WI(Han) rat with the similar to 110-kDa protein revealed a sequence that was identical to that of the CRL:WI and SD rat. However, cloning of the AhR from a rat with the similar to 97-kDa protein revealed a point mutation, and five variants encoding two C-terminally truncated variants of the AhR protein, arising from a point mutation in the intron/exon junction and consequent differential splicing. These C-terminally truncated variants were expressed and shown to give rise to a protein of similar to 97 kDa; the recombinant AhR bound TCDD with an affinity that was not statistically different from the full-length protein. A single-nucleotide polymorphism assay was developed, and showed that both alleles were represented in a Hardy-Weinberg equilibrium in samples of CRL:WI and CRL:WI(Han) populations; both alleles are abundant. Rats from two studies of TCDD developmental toxicity were genotyped, and the association with toxicity investigated using statistical analysis. There was no plausible evidence that the AhR allele had a significant effect on the toxic endpoints examined. These data show that the two AhR alleles are common in two strains of Wistar rat, and that the AhR alleles had no effect on TCDD-induced developmental toxicity in two independent studies.
C1 [Jiang, Tao; Bell, David R.; Fan, Ming Qi] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England.
[Fernandes, Alwyn; MacNicoll, Alan; Rose, Martin; White, Shaun] Environm Food & Hlth, Cent Sci Lab, York YO41 1LZ, N Yorkshire, England.
[Foster, Paul M. D.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Loizou, George] Hlth & Safety Lab, Buxton SK17 9JN, Derby, England.
[Miller, Brian G.; Tran, Lang] Inst Occupat Med, Edinburgh EH14 4AP, Midlothian, Scotland.
RP Bell, DR (reprint author), Univ Nottingham, Sch Biol, Univ Pk, Nottingham NG7 2RD, England.
EM david.bell@nottingham.ac.uk
OI Rose, Martin/0000-0001-7071-180X
FU Food Standards Agency [T01034]
FX Food Standards Agency (T01034).
NR 40
TC 3
Z9 3
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD FEB
PY 2009
VL 107
IS 2
BP 512
EP 521
DI 10.1093/toxsci/kfn252
PG 10
WC Toxicology
SC Toxicology
GA 398HK
UT WOS:000262723000021
PM 19056935
ER
PT J
AU Kienhuis, AS
van de Poll, MCG
Wortelboer, H
van Herwijnen, M
Gottschalk, R
Dejong, CHC
Boorsma, A
Paules, RS
Kleinjans, JCS
Stierum, RH
van Delft, JHM
AF Kienhuis, Anne S.
van de Poll, Marcel C. G.
Wortelboer, Heleen
van Herwijnen, Marcel
Gottschalk, Ralph
Dejong, Cornelis H. C.
Boorsma, Andre
Paules, Richard S.
Kleinjans, Jos C. S.
Stierum, Rob H.
van Delft, Joost H. M.
TI Parallelogram Approach Using Rat-Human In Vitro and Rat In Vivo
Toxicogenomics Predicts Acetaminophen-induced Hepatotoxicity in Humans
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
ID GENE-EXPRESSION; HUMAN HEPATOCYTES; CYTOCHROME-P450 EXPRESSION;
DRUG-METABOLISM; LIVER; TOXICITY; MECHANISMS; MICROARRAY; REVEALS;
MODELS
AB The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct comparison of toxicant-induced gene expression profiles and infers mechanisms between several systems. In the present study, acetaminophen (APAP) was used as a model compound to compare gene expression responses between rat and human using in vitro cellular models, hepatocytes, and between rat in vitro and in vivo. Comparison at the level of modulated biochemical pathways and biological processes rather than at that of individual genes appears preferable as it increases the overlap between various systems. Pathway analysis by T-profiler revealed similar biochemical pathways and biological processes repressed in rat and human hepatocytes in vitro, as well as in rat liver in vitro and in vivo. Repressed pathways comprised energy-consuming biochemical pathways, mitochondrial function, and oxidoreductase activity. The present study is the first that used a toxicogenomics-based parallelogram approach, extrapolating in vitro to in vivo and interspecies, to reveal relevant mechanisms indicative of APAP-induced liver toxicity in humans in vivo.
C1 [Kienhuis, Anne S.; van Herwijnen, Marcel; Gottschalk, Ralph; Kleinjans, Jos C. S.; van Delft, Joost H. M.] Univ Maastricht, Dept Hlth Risk Anal & Toxicol, NL-6200 MD Maastricht, Netherlands.
[Kienhuis, Anne S.; Wortelboer, Heleen; Boorsma, Andre; Stierum, Rob H.] TNO Qual Life, Business Unit Biosci, Zeist, Netherlands.
[van de Poll, Marcel C. G.; Dejong, Cornelis H. C.] Univ Maastricht, Nutr & Toxicol Res Inst NUTRIM, NL-6200 MD Maastricht, Netherlands.
[van de Poll, Marcel C. G.; Dejong, Cornelis H. C.] Univ Hosp Maastricht, Dept Surg, Maastricht, Netherlands.
[Paules, Richard S.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA.
RP Kienhuis, AS (reprint author), Univ Maastricht, Dept Hlth Risk Anal & Toxicol, POB 616, NL-6200 MD Maastricht, Netherlands.
EM anne.kienhuis@rivm.nl
RI Kleinjans, Jos/E-7241-2015
FU Netherlands Organization for Health Research and Development, program
Alternatives to Animal Experiments [3170.0049]; Dutch Ministry of
Economic Affairs
FX The Netherlands Organization for Health Research and Development,
program Alternatives to Animal Experiments (3170.0049); the Dutch
Ministry of Economic Affairs.
NR 37
TC 27
Z9 28
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD FEB
PY 2009
VL 107
IS 2
BP 544
EP 552
DI 10.1093/toxsci/kfn237
PG 9
WC Toxicology
SC Toxicology
GA 398HK
UT WOS:000262723000024
PM 19008212
ER
PT J
AU Nadadur, SS
Haykal-Coates, N
Mudipalli, A
Costa, DL
AF Nadadur, Srikanth S.
Haykal-Coates, Najwa
Mudipalli, Anuradha
Costa, Daniel L.
TI Endothelial effects of emission source particles: Acute toxic response
gene expression profiles
SO TOXICOLOGY IN VITRO
LA English
DT Article
DE Endothelial; Particulate matter; Vascular effects
ID OIL FLY-ASH; PARTICULATE AIR-POLLUTION; TRANSITION-METALS; EPIDEMIOLOGIC
EVIDENCE; ULTRAFINE PARTICLES; RESPIRATORY-TRACT; OXIDATIVE-STRESS;
DIESEL EXHAUST; LUNG INJURY; MATTER
AB Air pollution epidemiology has established a strong association between exposure to ambient particulate matter (PM) and cardiovascular outcomes. Experimental studies in both humans and laboratory animals Support varied biological mechanisms including endothelial dysfunction as potentially a central step to the elicitation of cardiovascular events. We therefore hypothesized that relevant early molecular alterations on endothelial cells should be assessable in vitro upon acute exposure to PM components previously shown to be involved in health outcomes. Using a model emission PM, residual oil fly ash and one of its predominant constituents (vanadium-V), we focused oil the development of gene expression profiles to fingerprint that particle and its constituents to explore potential biomarkers for PM-induced endothelial dysfunction. Here we present differential gene expression and transcription factor activation Profiles in human vascular endothelial cells exposed to a non-cytotoxic dose of fly ash or V following semi-global gene expression profiling of similar to 8000 genes. Both fly ash and it's prime constituent, V, induced alterations in genes involved in passive and active transport of solutes across the membrane; voltage-dependent ion pumps: induction of extracellular matrix proteins and adhesion molecules: and activation of numerous kinases involved in signal transduction pathways. These preliminary data suggest that cardiovascular effects associated with exposure to PM may be mediated by perturbations in endothelial cell permeability, membrane integrity; and ultimately endothelial dysfunction. Published by Elsevier Ltd.
C1 [Nadadur, Srikanth S.; Haykal-Coates, Najwa; Costa, Daniel L.] US EPA, ORD, Natl Hlth Environm Effects Res Lab, Pulm Toxicol Branch,Expt Toxicol Div, Res Triangle Pk, NC 27711 USA.
[Mudipalli, Anuradha] US EPA, ORD, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA.
RP Nadadur, SS (reprint author), NIEHS, Cellular & Organ Syst Pathobiol Branch, Div Extramural Res & Training, POB 12233,MD EC 23, Res Triangle Pk, NC 27709 USA.
EM Nadadurs@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]
NR 53
TC 16
Z9 19
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-2333
J9 TOXICOL IN VITRO
JI Toxicol. Vitro
PD FEB
PY 2009
VL 23
IS 1
BP 67
EP 77
DI 10.1016/j.tiv.2008.10.004
PG 11
WC Toxicology
SC Toxicology
GA 402LS
UT WOS:000263015800009
PM 19000753
ER
PT J
AU Rismanchi, N
Puertollano, R
Blackstone, C
AF Rismanchi, Neggy
Puertollano, Rosa
Blackstone, Craig
TI STAM Adaptor Proteins Interact with COPII Complexes and Function in
ER-to-Golgi Trafficking
SO TRAFFIC
LA English
DT Article
DE Brefeldin A; endocytosis; Golgi fragmentation; Sec31; VHS domain; VSV-G
ID ENDOPLASMIC-RETICULUM; GAMMA-ADAPTIN; SIGNALING PATHWAYS;
MAMMALIAN-CELLS; EARLY ENDOSOME; JANUS KINASES; LIVING CELLS; EXIT
SITES; VHS DOMAIN; HRS
AB Signal-transducing adaptor molecules (STAMs) are involved in growth factor and cytokine signaling as well as receptor degradation, and they form complexes with a number of endocytic proteins, including Hrs and Eps15. In this study, we demonstrate that STAM proteins also localize prominently to early exocytic compartments and profoundly regulate Golgi morphology. Upon STAM overexpression in cells, the Golgi apparatus becomes extensively fragmented and dispersed, but when STAMs are depleted, the Golgi becomes highly condensed. Under both scenarios, vesicular stomatitis virus G protein-green fluorescent protein trafficking to the plasma membrane is markedly inhibited, and recovery of Golgi morphology after Brefeldin A treatment is substantially impaired in STAM-depleted cells. Furthermore, STAM proteins interact with coat protein II (COPII) proteins, probably at endoplasmic reticulum (ER) exit sites, and Sar1 activity is required to maintain the localization of STAMs at discrete sites. Thus, in addition to their roles in signaling and endocytosis, STAMs function prominently in ER-to-Golgi trafficking, most likely through direct interactions with the COPII complex.
C1 [Rismanchi, Neggy; Blackstone, Craig] NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Rismanchi, Neggy] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA.
[Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov
FU NINDS and NHLBI; National Institutes of Health
FX We thank James Nagle and Deborah Kauffman (NINDS DNA Sequencing
Facility) for DNA sequencing, Carolyn Smith for assistance with confocal
microscopy, Jung-Hwa Tao-Cheng for assistance with electron microscopy
and Chuang-Rung Chang for helpful discussions. This work was supported
by the Intramural Research Programs of the NINDS and NHLBI, National
Institutes of Health.
NR 44
TC 13
Z9 14
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD FEB
PY 2009
VL 10
IS 2
BP 201
EP 217
DI 10.1111/j.1600-0854.2008.00856.x
PG 17
WC Cell Biology
SC Cell Biology
GA 395FW
UT WOS:000262511000007
PM 19054391
ER
PT J
AU Hayashi, T
Rizzuto, R
Hajnoczky, G
Su, TP
AF Hayashi, Teruo
Rizzuto, Rosario
Hajnoczky, Gyorgy
Su, Tsung-Ping
TI MAM: more than just a housekeeper
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID RAT-LIVER MITOCHONDRIA; SMOOTH ENDOPLASMIC-RETICULUM; PERMEABILIZED
ANIMAL-CELLS; SIGMA(1) BINDING-SITES; HAMSTER OVARY CELLS; TRISPHOSPHATE
RECEPTORS; MEDIATED APOPTOSIS; MEMBRANE-FRACTION; PLASMA-MEMBRANE; CA2+
AB The physical association between the endoplasmic reticulum (ER) and mitochondria, which is known as the mitochondria-associated ER membrane (MAM), has important roles in various cellular 'housekeeping' functions including the non-vesicular transports of phospholipids. It has recently become clear that the MAM also enables highly efficient transmission of Ca(2+) from the ER to mitochondria to stimulate oxidative metabolism and, conversely, might enable the metabolically energized mitochondria to regulate the ER Ca(2+) homeostasis. Recent studies have shed light on molecular chaperones such as calnexin, calreticulin, ERp44, ERp57, grp75 and the sigma-1 receptor at the MAM, which regulate the association between the two organelles. The MAM thus integrates signal transduction with metabolic pathways to regulate the communication and functional interactions between the ER and mitochondrion.
C1 [Hayashi, Teruo; Su, Tsung-Ping] Natl Inst Drug Abuse, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Rizzuto, Rosario] Univ Ferrara, Dept Expt & Diagnost Med, Sect Gen Pathol, ER GenTech Lab, I-44100 Ferrara, Italy.
[Rizzuto, Rosario] Univ Ferrara, Interdisciplinary Ctr Study Inflammat, I-44100 Ferrara, Italy.
[Hajnoczky, Gyorgy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
RP Su, TP (reprint author), Natl Inst Drug Abuse, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tsu@mail.nih.gov
OI Rizzuto, Rosario/0000-0001-7044-5097
FU National Institute on Drug Abuse; National Institutes of Health;
Department of Health and Human Services of the USA
FX This work supported in part by the Intramural Research Program of the
National Institute on Drug Abuse, the National Institutes of Health and
the Department of Health and Human Services of the USA.
NR 65
TC 312
Z9 321
U1 3
U2 23
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD FEB
PY 2009
VL 19
IS 2
BP 81
EP 88
DI 10.1016/j.tcb.2008.12.002
PG 8
WC Cell Biology
SC Cell Biology
GA 413DS
UT WOS:000263773700005
PM 19144519
ER
PT J
AU Roy, SW
Irimia, M
AF Roy, Scott William
Irimia, Manuel
TI Mystery of intron gain: new data and new models
SO TRENDS IN GENETICS
LA English
DT Review
ID DIATOM THALASSIOSIRA-PSEUDONANA; CHORDATE OIKOPLEURA-DIOICA; CODON USAGE
BIAS; GROUP-II INTRONS; REVERSE-TRANSCRIPTION; SPLICEOSOMAL INTRONS;
CRYPTOCOCCUS-NEOFORMANS; EUKARYOTIC EVOLUTION; GENES; GENOME
AB Despite their ubiquity, the mechanisms and evolutionary forces responsible for the origins of spliceosomal introns remain mysterious. Recent molecular evidence supports the idea that intronic RNAs can reverse splice into RNA transcripts, a crucial step for an influential model of intron gain. However, a paradox attends this model because the rate of intron gain is expected to be orders of magnitude lower than the rate of intron loss in general, in contrast to findings from several lineages. We suggest two possible resolutions to this paradox, based on steric considerations and on the possibility of cooption by specific introns of retroelement transposition pathways, respectively. In addition, we introduce two potential mechanisms for intron creation, based on hybrid RNA-DNA reverse splicing and on template switching errors by reverse transcriptase.
C1 [Roy, Scott William] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Spain.
RP Roy, SW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
EM royscott@ncbi.nlm.nih.gov
RI Irimia, Manuel/E-3040-2010;
OI Irimia, Manuel/0000-0002-2179-2567
FU Spanish Ministerio of Educacion y Ciencia [BFU2005-00252]; National
Library of Medicine at National Institutes of Health
FX M.I. was funded by the Spanish Ministerio of Educacion y Ciencia,
through a FPI grant (BFU2005-00252) and S.W.R. by the Intramural
Research Program of the National Library of Medicine at National
Institutes of Health. We thank Eugene Koonin and Jordi Garcia-Fernandez
for support.
NR 63
TC 45
Z9 45
U1 3
U2 13
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD FEB
PY 2009
VL 25
IS 2
BP 67
EP 73
DI 10.1016/j.tig.2008.11.004
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 415IF
UT WOS:000263926800003
PM 19070397
ER
PT J
AU Aronova, MA
Kim, YC
Pivovarova, NB
Andrews, SB
Leapman, RD
AF Aronova, M. A.
Kim, Y. C.
Pivovarova, N. B.
Andrews, S. B.
Leapman, R. D.
TI Quantitative EFTEM mapping of near physiological calcium concentrations
in biological specimens
SO ULTRAMICROSCOPY
LA English
DT Article
DE Energy-filtered transmission electron microscopy (EFTEM); Electron
energy-loss spectroscopy (EELS); Plural scattering; Elemental mapping;
Calcium; Detection limits
ID ENERGY-LOSS SPECTROSCOPY; SPATIAL DISTRIBUTIONS; LOSS SPECTRA; ELECTRON;
MITOCHONDRIA; PHOSPHORUS; MICROANALYSIS; NEURONS; FILTER; TOMOGRAPHY
AB Although electron energy-loss spectroscopy (EELS) in the scanning transmission electron microscope (STEM) provides high sensitivity for measuring the important element, calcium, in biological specimens, the technique has been difficult to apply routinely, because of long acquisition times required. Here we describe a refinement of the complementary analytical technique of energy-filtered transmission electron microscopy (EFTEM), which enables rapid imaging of large cellular regions and measurement of calcium concentrations approaching physiological levels. Extraction of precise quantitative information is possible by averaging large numbers of pixels that are contained in organelles of interest. We employ a modified two-window approach in which the behavior of the background signal in the EELS spectrum can be modeled as a function of specimen thickness t expressed in terms of the inelastic mean free path lambda. By acquiring pairs of images, one above and one below the Ca L(2.3) edge, together with zero-loss and unfiltered images, which are used to determine a relative thickness (t/lambda) map, it is possible to correct the Ca L(2.3) signal for plural scattering. We have evaluated the detection limits of this technique by considering several sources of systematic errors and applied this method to determine mitochondrial total calcium concentrations in freeze-dried cryosections of rapidly frozen stimulated neurons. By analyzing 0.1 mu m(2) areas of specimen regions that do not contain calcium, it was found that the standard deviation in the measurement of Ca concentrations was about 20 mmol/kg dry weight, corresponding to a Ca:C atomic fraction of approximately 2 x 10(-4). Calcium concentrations in peripheral mitochondria of recently depolarized, and therefore stimulated and Ca loaded, frog sympathetic neurons were in reasonable agreement with previous data. Published by Elsevier B.V.
C1 [Aronova, M. A.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Kim, Y. C.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Pivovarova, N. B.; Andrews, S. B.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bldg 13,Rm 3N17,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leapmanr@mail.nih.gov
FU National Institute of Biomedical Imaging and Bioengineering; National
Institute of Neurological Disorders and Stroke, National Institutes of
Health
FX This research was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering and the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 40
TC 19
Z9 19
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3991
J9 ULTRAMICROSCOPY
JI Ultramicroscopy
PD FEB
PY 2009
VL 109
IS 3
BP 201
EP 212
DI 10.1016/j.ultramic.2008.10.003
PG 12
WC Microscopy
SC Microscopy
GA 420HQ
UT WOS:000264280200001
PM 19118952
ER
PT J
AU Sousa, AA
Hohmann-Marriott, MF
Zhang, G
Leapman, RD
AF Sousa, A. A.
Hohmann-Marriott, M. F.
Zhang, G.
Leapman, R. D.
TI Monte Carlo electron-trajectory simulations in bright-field and
dark-field STEM: Implications for tomography of thick biological
sections
SO ULTRAMICROSCOPY
LA English
DT Article
DE Scanning transmission electron microscopy; STEM; Electron tomography;
Monte Carlo simulation; Thick sections
ID AMORPHOUS SPECIMENS; SPATIAL-RESOLUTION; IMAGE-FORMATION; ENERGY-LOSS;
MICROSCOPY; RECONSTRUCTION; SCATTERING; CONTRAST; LABELS; CELLS
AB A Monte Carlo electron-trajectory calculation has been implemented to assess the optimal detector configuration for scanning transmission electron microscopy (STEM) tomography of thick biological sections. By modeling specimens containing 2 and 3 at% osmium in a carbon matrix, it was found that for 1-mu m-thick samples the bright-field (BF) and annular dark-field (ADF) signals give similar contrast and signal-to-noise ratio provided the ADF inner angle and BF outer angle are chosen optimally. Spatial resolution in STEM imaging of thick sections is compromised by multiple elastic scattering which results in a spread of scattering angles and thus a spread in lateral distances of the electrons leaving the bottom surface. However, the simulations reveal that a large fraction of these multiply scattered electrons are excluded from the BF detector, which results in higher spatial resolution in BF than in high-angle ADF images for objects situated towards the bottom of the sample. The calculations imply that STEM electron tomography of thick sections should be performed using a BF rather than an ADF detector. This advantage was verified by recording simultaneous BF and high-angle ADF STEM tomographic tilt series from a stained 600-nm-thick section of C elegans. It was found that loss of spatial resolution occurred markedly at the bottom surface of the specimen in the ADF STEM but significantly less in the BF STEM tomographic reconstruction. Our results indicate that it might be feasible to use BF STEM tomography to determine the 3D structure of whole eukaryotic microorganisms prepared by freeze-substitution, embedding, and sectioning. Published by Elsevier B.V.
C1 [Sousa, A. A.; Hohmann-Marriott, M. F.; Zhang, G.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bldg 13,Rm 3N17,13 S Dr, Bethesda, MD 20892 USA.
EM leapmanr@mail.nih.gov
FU National institute of Biomedical Imaging and Bioengineering, National
Institutes of Health; National Institute of Standards and Technology and
NIBIB, NIH
FX This work was supported by the Intramural Research Program of the
National institute of Biomedical Imaging and Bioengineering, National
Institutes of Health. MFHM would like to acknowledge support of a US
National Research Council Postdoctoral Associateship co-funded by the
National Institute of Standards and Technology and NIBIB, NIH.
NR 38
TC 25
Z9 25
U1 0
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3991
J9 ULTRAMICROSCOPY
JI Ultramicroscopy
PD FEB
PY 2009
VL 109
IS 3
BP 213
EP 221
DI 10.1016/j.ultramic.2008.10.005
PG 9
WC Microscopy
SC Microscopy
GA 420HQ
UT WOS:000264280200002
PM 19110374
ER
PT J
AU Robey, RW
To, KKK
Polgar, O
Dohse, M
Fetsch, P
Dean, M
Bates, SE
AF Robey, Robert W.
To, Kenneth K. K.
Polgar, Orsolya
Dohse, Marius
Fetsch, Patricia
Dean, Michael
Bates, Susan E.
TI ABCG2: A perspective
SO ADVANCED DRUG DELIVERY REVIEWS
LA English
DT Review
DE ABCG2; BCRP; Drug-resistance; ABC transporter; Chemotherapy;
Pharmacology
ID CANCER-RESISTANCE-PROTEIN; BLOOD-BRAIN-BARRIER; MULTIDRUG TRANSPORTER
ABCG2; LIMITS FETAL DISTRIBUTION; HIGH-AFFINITY INTERACTION;
HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOID-LEUKEMIA; NORMAL HUMAN
TISSUES; BREAST-CANCER; P-GLYCOPROTEIN
AB ABCG2, or breast cancer resistance protein (BCRP), is an ABC transporter that has been the subject of intense study since its discovery a decade ago. With high normal tissue expression in the brain endothelium, gastrointestinal tract, and placenta, ABCG2 is believed to be important in the protection from xenobiotics, regulating oral bioavailability, forming part of the blood-brain barrier, the blood-testis barrier, and the maternal-fetal barrier. Notably, ABCG2 is often expressed in stem cell populations, where it likely plays a role in xenobiotic protection. However, clues to its epigenetic regulation in various cell populations are only beginning to emerge. While ABCG2 overexpression has been demonstrated in cancer cells after in vitro drug treatment, endogenous ABCG2 expression in certain cancers is likely a reflection of the differentiated phenotype of the cell of origin and likely contributes to intrinsic drug resistance. Notably, research into the transporter's role in cancer drug resistance and its development as a therapeutic target in cancer has lagged. Substrates and inhibitors of the transporter have been described, among them chemotherapy drugs, tyrosine kinase inhibitors, antivirals, HMG-CoA reductase inhibitors, carcinogens, and flavonoids. This broad range of substrates complements the efficiency of ABCG2 as a transporter in laboratory studies and suggests that, while there are redundant mechanisms of xenobiotic protection, the protein is important in normal physiology. indeed, emerging studies in pharmacology and toxicology assessing polymorphic variants in man, in combination with murine knockout models have confirmed its dynamic role. Work in pharmacology may eventually lead us to a greater understanding of the physiologic role of ABCG2. (C) 2008 Published by Elsevier B.V.
C1 [Robey, Robert W.; To, Kenneth K. K.; Polgar, Orsolya; Dohse, Marius; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fetsch, Patricia] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dean, Michael] Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA.
RP Bates, SE (reprint author), 9000 Rockville Pike,Bldg 10 Rm 13N, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
RI Dean, Michael/G-8172-2012; To, Kenneth /M-4500-2013
OI Dean, Michael/0000-0003-2234-0631; To, Kenneth /0000-0003-2755-0283
FU Intramural NIH HHS [Z99 CA999999]
NR 159
TC 213
Z9 223
U1 3
U2 29
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-409X
J9 ADV DRUG DELIVER REV
JI Adv. Drug Deliv. Rev.
PD JAN 31
PY 2009
VL 61
IS 1
BP 3
EP 13
DI 10.1016/j.addr.2008.11.003
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 414HT
UT WOS:000263855200002
PM 19135109
ER
PT J
AU Pistell, PJ
Nelson, CM
Miller, MG
Spangler, EL
Ingram, DK
Devan, BD
AF Pistell, Paul J.
Nelson, Chris M.
Miller, Marshall G.
Spangler, Edward L.
Ingram, Donald K.
Devan, Bryan D.
TI Striatal lesions interfere with acquisition of a complex maze task in
rats
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Striatum; Maze; Learning; Excitotoxic lesion; Rats
ID 14-UNIT T-MAZE; FIMBRIA-FORNIX LESIONS; CAUDATE-PUTAMEN LESIONS;
NITRIC-OXIDE; WATER MAZE; LEARNING IMPAIRMENT; DORSAL STRIATUM;
PHOSPHODIESTERASE INHIBITION; RETENTION PERFORMANCE; DOUBLE DISSOCIATION
AB The 14-unit T-maze has proven to be a valuable tool for investigating age-associated memory impairment (AAMI). While another task widely used to evaluate AAMI, the water maze, is primarily used to evaluate allocentric hippocampal-dependent spatial memory, the 14-unit T-maze can assess egocentric procedural memory. Although several brain structures, e.g. hippocampus, parietal cortex have been implicated in, acquisition and retention performance in the 14-unit T-maze, there has been no evaluation of the involvement of the striatum, a brain region implicated in procedural learning and memory. The current study revealed that excitotoxic lesions of the medial or lateral striatum significantly impaired acquisition, as measured by errors and latency, on this task without disruption of motor function. These results indicate that the 14-unit T-maze most likely is requires a large egocentric procedural learning component, and previously observed AAMI may involve age-related dysfunction of the striatum. Published by Elsevier B.V.
C1 [Pistell, Paul J.; Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
[Pistell, Paul J.; Nelson, Chris M.; Miller, Marshall G.; Spangler, Edward L.; Ingram, Donald K.; Devan, Bryan D.] NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Devan, Bryan D.] Towson Univ, Dept Psychol, Lab Comparat Neuropsychol, Towson, MD 21252 USA.
RP Pistell, PJ (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM Paul.Pistell@pbrc.edu
FU Intramural Research Program of the NIH, National Institute on Aging
[Z01AG00302-24, 1P20 RR02/1945]; CNRU [1P30 DK072476]; NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging (Z01AG00302-24). Christopher Quigley
provided assistance with the histological preparation. Histological
analysis of the lesions utilized the facilities of the Cell Biology and
Bioimaging Core facilities at the Pennington Biomedical Research Center
supported by NIH Grant 1P20 RR02/1945 and a CNRU center grant # 1P30
DK072476 sponsored by NIDDK.
NR 48
TC 16
Z9 16
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JAN 30
PY 2009
VL 197
IS 1
BP 138
EP 143
DI 10.1016/j.bbr.2008.08.015
PG 6
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 396MU
UT WOS:000262596600018
PM 18789359
ER
PT J
AU So, JH
Chun, HS
Bae, YK
Kim, HS
Park, YM
Huh, TL
Chitnis, AB
Kim, CH
Yeo, SY
AF So, Ju-Hoon
Chun, Hang-Suk
Bae, Yong-Ki
Kim, Hyun-Seo
Park, Yeoll-Mae
Huh, Tae-Lin
Chitnis, Ajay B.
Kim, Cheol-Hee
Yeo, Sang-Yeob
TI Her4 is necessary for establishing peripheral projections of the
trigeminal ganglia in zebrafish
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Her4; Zebrafish; Notch signaling; Trigeminal ganglia; Neural progenitor;
Peripheral projections
ID EARLY NEUROGENESIS; DROSOPHILA-MELANOGASTER; EMBRYONIC ZEBRAFISH; NOTCH;
GENE; PROTEINS; HOMOLOG; DELTA; SUPPRESSOR; EXPRESSION
AB Transcripts of notch and its target genes have been detected in some differentiating neurons. However, the role of Notch in neuronal differentiation remains poorly defined. Here, we show that a subset of differentiating sensory neurons in the trigeminal ganglia express her4. Expression of her4 requires Notch signaling during neurogenesis but not during differentiation, when peripheral projections of the trigeminal ganglia are established. These projections develop poorly in her4 morphants. While many components of the canonical Notch signaling pathway are not required for late her4 expression or peripheral axon outgrowth in trigeminal neurons, simultaneous knock-down of Notch receptors prevents establishment of these peripheral projections. These observations suggest that Her4 and Notch play a role in peripheral outgrowth of sensory neurons. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Kim, Hyun-Seo; Park, Yeoll-Mae; Yeo, Sang-Yeob] Hanbat Natl Univ, Dept Biotechnol, Div Appl Chem & Biotechnol, Taejon 305719, South Korea.
[Chun, Hang-Suk; Huh, Tae-Lin] Kyungpook Natl Univ, Dept Gen Engn, Taegu 702701, South Korea.
[Bae, Yong-Ki] Natl Canc Ctr, Res Inst, Div Basic & Appl Sci, Canc Expt Resources Branch, Gyeonggi Do 410769, South Korea.
[Chitnis, Ajay B.] NICHD, Sect Neural Dev Dynam, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[So, Ju-Hoon; Kim, Cheol-Hee] Chungnam Natl Univ, Dept Biol, Taejon 305764, South Korea.
RP Yeo, SY (reprint author), Hanbat Natl Univ, Dept Biotechnol, Div Appl Chem & Biotechnol, Taejon 305719, South Korea.
EM yeosy@hanbat.ac.kr
FU Korean Government (MOEHRD, Basic Research Promotion Fund)
[KRF-2007-313-C00603]
FX The authors thank members of the Chitnis, Hull, Kim, and Yeo
laboratories. We are indebted to V.T. Cunliffe for providing the hdac1
MO. This work was supported by a Korea Research Foundation Grant funded
by the Korean Government (MOEHRD, Basic Research Promotion Fund)
(KRF-2007-313-C00603).
NR 20
TC 6
Z9 6
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 30
PY 2009
VL 379
IS 1
BP 22
EP 26
DI 10.1016/j.bbrc.2008.11.149
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 401DA
UT WOS:000262917500005
PM 19084503
ER
PT J
AU Tai, CH
Vincent, JJ
Kim, C
Lee, B
AF Tai, Chin-Hsien
Vincent, James J.
Kim, Changhoon
Lee, Byungkook
TI SE: an algorithm for deriving sequence alignment from a pair of
superimposed structures
SO BMC BIOINFORMATICS
LA English
DT Article
CT 9th Asia Pacific Bioinformatics Conference
CY JAN 13-16, 2009
CL Tsinghua Univ, Beijing, PEOPLES R CHINA
HO Tsinghua Univ
ID PROTEIN-STRUCTURE ALIGNMENT; GLUTAMINE-SYNTHETASE; UCSF CHIMERA;
DATABASE; ACCURACY; FAMILIES
AB Background: Generating sequence alignments from superimposed structures is an important part of many structure comparison programs. The accuracy of the alignment affects structure recognition, classification and possibly function prediction. Many programs use a dynamic programming algorithm to generate the sequence alignment from superimposed structures. However, this procedure requires using a gap penalty and, depending on the value of the penalty used, can introduce spurious gaps and misalignments. Here we present a new algorithm, Seed Extension (SE), for generating the sequence alignment from a pair of superimposed structures. The SE algorithm first finds "seeds", which are the pairs of residues, one from each structure, that meet certain stringent criteria for being structurally equivalent. Three consecutive seeds form a seed segment, which is extended along the diagonal of the alignment matrix in both directions. Distance and the amino acid type similarity between the residues are used to resolve conflicts that arise during extension of more than one diagonal. The manually curated alignments in the Conserved Domain Database were used as the standard to assess the quality of the sequence alignments.
Results: SE gave an average accuracy of 95.9% over 582 pairs of superimposed proteins tested, while CHIMERA, LSQMAN, and DP extracted from SHEBA, which all use a dynamic programming algorithm, yielded 89.9%, 90.2% and 91.0%, respectively. For pairs of proteins with low sequence or structural similarity, SE produced alignments up to 18% more accurate on average than the next best scoring program. Improvement was most pronounced when the two superimposed structures contained equivalent helices or beta-strands that crossed at an angle. When the SE algorithm was implemented in SHEBA to replace the dynamic programming routine, the alignment accuracy improved by 10% on average for structure pairs with RMSD between 2 and 4 angstrom. SE also used considerably less CPU time than DP.
Conclusion: The Seed Extension algorithm is fast and, without using a gap penalty, produces more accurate sequence alignments from superimposed structures than three other programs tested that use dynamic programming algorithm.
C1 [Tai, Chin-Hsien; Vincent, James J.; Kim, Changhoon; Lee, Byungkook] NCI, Mol Modeling & Bioinformat Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Vincent, James J.] Univ Vermont, Dept Biol, Vermont Genet Network, Burlington, VT 05405 USA.
RP Lee, B (reprint author), NCI, Mol Modeling & Bioinformat Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM taic@mail.nih.gov; jjv5@uvm.edu; kimchan@mail.nih.gov;
bklee@mail.nih.gov
FU Intramural NIH HHS
NR 21
TC 6
Z9 6
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JAN 30
PY 2009
VL 10
AR S4
DI 10.1186/1471-2105-10-S1-S4
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 439BN
UT WOS:000265601900004
PM 19208141
ER
PT J
AU Azzato, EM
Morton, LM
Bergen, AW
Wang, SS
Chatterjee, N
Kvale, P
Yeager, M
Hayes, RB
Chanock, SJ
Caporaso, NE
AF Azzato, Elizabeth M.
Morton, Lindsay M.
Bergen, Andrew W.
Wang, Sophia S.
Chatterjee, Nilanjan
Kvale, Paul
Yeager, Meredith
Hayes, Richard B.
Chanock, Stephen J.
Caporaso, Neil E.
TI SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial
SO BMC MEDICAL GENETICS
LA English
DT Article
ID DOPAMINE TRANSPORTER GENE; AFRICAN-AMERICAN SMOKERS; GENOME-WIDE
ASSOCIATION; UNITED-STATES; ANOREXIA-NERVOSA; VARIABLE NUMBER; VNTR
POLYMORPHISMS; SMOKING-CESSATION; CIGARETTE-SMOKING; ADULT OBESITY
AB Background: To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Methods: Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (< 18.5, 18.5-24.9, 25.0-29.9, or >= 30 kg/m(2), respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression.
Results: Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR(*9) = 0.80, OR(99) = 0.47, P(trend) = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; OR(A-C-G-9) = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; OR(A-C-G-9) = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3' variant allele (A-C-G-9).
Conclusion: Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.
C1 [Azzato, Elizabeth M.; Morton, Lindsay M.; Wang, Sophia S.; Chatterjee, Nilanjan; Hayes, Richard B.; Caporaso, Neil E.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Azzato, Elizabeth M.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England.
[Bergen, Andrew W.] SRI Int, Hlth Sci Ctr, Menlo Pk, CA 94025 USA.
[Kvale, Paul] Henry Ford Hlth Syst, Detroit, MI USA.
[Yeager, Meredith; Chanock, Stephen J.] SAIC Frederick Inc, NCI Frederick, Core Genotyping Facil, Div Canc Epidemiol & Genet,Adv Technol Program, Frederick, MD USA.
RP Azzato, EM (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
EM ema32@cam.ac.uk; mortonli@mail.nih.gov; andrew.bergen@sri.com;
wangso@mail.nih.gov; chattern@mail.nih.gov; pkvale1@hfhs.org;
my76y@nih.gov; hayesr@mail.nih.gov; sc83a@nih.gov;
caporasn@epndce.nci.nih.gov
RI Morton, Lindsay/B-5234-2015; Azzato, Elizabeth/A-1902-2009;
OI Morton, Lindsay/0000-0001-9767-2310; Bergen, Andrew/0000-0002-1237-7644;
Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
Clinical Research Training Program; NIH and Pfizer Inc; NCI;
NIH/University of Cambridge; National Cancer Institute [U01 DA020830]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract N01-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
EMA was funded through the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer Inc
(via a grant to the Foundation for NIH from Pfizer Inc) and is currently
funded through the NCI and the NIH/University of Cambridge Graduate
Partnership Program. AWB was supported by the Intramural Research
Program of the National Cancer Institute and is supported by U01
DA020830.
NR 59
TC 4
Z9 4
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JAN 30
PY 2009
VL 10
AR 9
DI 10.1186/1471-2350-10-9
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 418MW
UT WOS:000264153300001
PM 19183461
ER
PT J
AU Mueller, M
Peters, FT
Huestis, MA
Ricaurte, GA
Maurer, HH
AF Mueller, Melanie
Peters, Frank T.
Huestis, Marilyn A.
Ricaurte, George A.
Maurer, Hans H.
TI Simultaneous liquid chromatographic-electrospray ionization mass
spectrometric quantification of 3,4-methylenedioxymethamphetamine (MDMA,
Ecstasy) and its metabolites 3,4-dihydroxymethamphetamine,
4-hydroxy-3-methoxymethamphetamine and 3,4-methylenedioxyamphetamine in
squirrel monkey and human plasma after acidic conjugate cleavage
SO FORENSIC SCIENCE INTERNATIONAL
LA English
DT Article
DE MDMA; Metabolites; LC-ESI-MS; Human plasma; Validation; Acidic
hydrolysis
ID FORENSIC TOXICOLOGY; DOPING CONTROL; AMPHETAMINE; NEUROTOXICITY; DRUGS;
PHARMACOLOGY; GLUTATHIONE; ANIMALS; ASSAY
AB 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a psychoactive drug with abuse liability and neurotoxic potential. Specimen preparation of a recently presented LC-MS assay with electrospray ionization for quantifying MDMA and its main metabolites in squirrel monkey plasma was modified to include acidic hydrolysis to obtain total 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. Method re-validation for squirrel monkey plasma and full validation for human plasma showed selectivity for all analytes. Recoveries were >= 71.0%. Changed specimen preparation or matrix did not affect accuracy or precision. No instability was observed after repeated freezing or in processed samples. Plasma MDMA and metabolites quantification, derived pharmacokinetic and toxicokinetic data and neurotoxicity research will benefit from this validated method. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Mueller, Melanie; Peters, Frank T.; Maurer, Hans H.] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany.
[Mueller, Melanie; Ricaurte, George A.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Maurer, HH (reprint author), Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany.
EM hans.maurer@uks.eu
FU USPHS [DA05707]
FX The authors thank Armin A. Weber for his technical support. This work
was supported by USPHS grant DA05707.
NR 27
TC 11
Z9 13
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0379-0738
J9 FORENSIC SCI INT
JI Forensic Sci.Int.
PD JAN 30
PY 2009
VL 184
IS 1-3
BP 64
EP 68
DI 10.1016/j.forsciint.2008.12.002
PG 5
WC Medicine, Legal
SC Legal Medicine
GA 408IV
UT WOS:000263429600012
PM 19131196
ER
PT J
AU Barros, SA
Srimaroeng, C
Perry, JL
Walden, R
Dembla-Rajpal, N
Sweet, DH
Pritchard, JB
AF Barros, Scott A.
Srimaroeng, Chutima
Perry, Jennifer L.
Walden, Ramsey
Dembla-Rajpal, Neetu
Sweet, Douglas H.
Pritchard, John B.
TI Activation of Protein Kinase C zeta Increases OAT1 (SLC22A6)- and OAT3
(SLC22A8)-mediated Transport
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ORGANIC ANION TRANSPORT; BREAST-CANCER CELLS; SUBSTRATE-SPECIFICITY;
CELLULAR PHYSIOLOGY; SULFATE TRANSPORT; PROXIMAL TUBULES; LLC-PK1 CELLS;
PDZ; KIDNEY; MEMBRANE
AB Organic anion transporters (OATs) play a pivotal role in the clearance of small organic anions by the kidney, yet little is known about how their activity is regulated. A yeast two-hybrid assay was used to identify putative OAT3-associated proteins in the kidney. Atypical protein kinase C zeta(PKC zeta) was shown to bind to OAT3. Binding was confirmed in immunoprecipitation assays. The OAT3/PKC zeta interaction was investigated in rodent renal cortical slices from fasted animals. Insulin, an upstream activator of PKC zeta, increased both OAT3-mediated uptake of estrone sulfate (ES) and PKC zeta activity. Both effects were abolished by a PKC zeta-specific pseudosubstrate inhibitor. Increased ES transport was not observed in renal slices from OAT3-null mice. Transport of the shared OAT1/OAT3 substrate, p-aminohippurate, behaved similarly, except that stimulation was reduced, not abolished, in the OAT3-null mice. This suggested that OAT1 activity was also modified by PKC zeta, subsequently confirmed using an OAT1-specific substrate, adefovir. Inhibition of PKC zeta also blocked the increase in ES uptake seen in response to epidermal growth factor and to activation of protein kinase A. Thus, PKC zeta acted downstream of the epidermal growth factor to protein kinase A signaling pathway. Activation of transport was accompanied by an increase in V(max) and was blocked by microtubule disruption, indicating that activation may result from trafficking of OAT3 into the plasma membrane. These data demonstrate that PKC zeta activation up-regulates OAT1 and OAT3 function, and that protein-protein interactions play a central role controlling these two important renal drug transporters.
C1 [Barros, Scott A.; Srimaroeng, Chutima; Perry, Jennifer L.; Walden, Ramsey; Dembla-Rajpal, Neetu; Pritchard, John B.] NIEHS, NIH, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
[Sweet, Douglas H.] Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA.
RP Pritchard, JB (reprint author), 111 TW Alexander Dr,MD F1-03, Res Triangle Pk, NC 27709 USA.
EM pritcha3@niehs.nih.gov
RI Sweet, Douglas/H-7914-2013
OI Sweet, Douglas/0000-0002-8911-9184
FU National Institutes of Health Intramural Research Program from the NIEHS
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program from the NIEHS. The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact. 1
Both authors contributed equally to this study.
NR 30
TC 23
Z9 23
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 JAN 30
PY 2009
VL 284
IS 5
BP 2672
EP 2679
DI 10.1074/jbc.M808078200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 397ZL
UT WOS:000262700900009
PM 19028678
ER
PT J
AU Burns, KE
Liu, WT
Boshoff, HIM
Dorrestein, PC
Barry, CE
AF Burns, Kristin E.
Liu, Wei-Ting
Boshoff, Helena I. M.
Dorrestein, Pieter C.
Barry, Clifton E.
TI Proteasomal Protein Degradation in Mycobacteria Is Dependent upon a
Prokaryotic Ubiquitin-like Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TUBERCULOSIS PROTEASOME; 20S PROTEASOME; GENE; FAMILY; IDENTIFICATION;
RHODOCOCCUS; PRECURSOR; COMPLEX; KIN
AB The striking identification of an apparent proteasome core in Mycobacteria and allied actinomycetes suggested that additional elements of this otherwise strictly eukaryotic system for regulated protein degradation might be conserved. The genes encoding this prokaryotic proteasome are clustered in an operon with a short open reading frame that encodes a small protein of 64 amino acids resembling ubiquitin with a carboxyl-terminal di-glycine-glutamine motif ( herein called Pup for prokaryotic ubiquitin-like protein). Expression of a polyhistidine-tagged Pup followed by pulldown revealed that a broad spectrum of proteins were post-translationally modified by Pup. Two-dimensional gel electrophoresis allowed us to conclusively identify two targets of this modification as myoinositol-1-phosphate synthase and superoxide dismutase. Deletion of the penultimate di-glycine motif or the terminal glutamine completely abrogated modification of cellular proteins with Pup. Further mass spectral analysis demonstrated that Pup was attached to a lysine residue on its target protein via the carboxyl-terminal glutamine with deamidation of this residue. Finally, we showed that cell lysates of wild type ( but not a proteasome mutant) efficiently degraded Pup-modified proteins. These data therefore establish that, despite differences in both sequence and target linkage, Pup plays an analogous role to ubiquitin in targeting proteins to the proteasome for degradation.
C1 [Burns, Kristin E.; Boshoff, Helena I. M.; Barry, Clifton E.] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
[Liu, Wei-Ting; Dorrestein, Pieter C.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmacol, La Jolla, CA 92093 USA.
[Liu, Wei-Ting; Dorrestein, Pieter C.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Dept Chem & Biochem, La Jolla, CA 92093 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov
RI Dorrestein, Pieter/D-5012-2012; Barry, III, Clifton/H-3839-2012
FU National Institutes of Health; Intramural Research Program, NIAID
FX This work was supported, in whole or in part, by the National Institutes
of Health, Intramural Research Program, NIAID. The costs of publication
of this article were defrayed in part by the payment of page charges.
This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 29
TC 77
Z9 88
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 30
PY 2009
VL 284
IS 5
BP 3069
EP 3075
DI 10.1074/jbc.M808032200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 397ZL
UT WOS:000262700900051
PM 19028679
ER
PT J
AU Topol, LL
Chen, W
Song, H
Day, TF
Yang, YZ
AF Topol, Lilia
Chen, Wen
Song, Hai
Day, Timothy F.
Yang, Yingzi
TI Sox9 Inhibits Wnt Signaling by Promoting beta-Catenin Phosphorylation in
the Nucleus
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AUTOSOMAL SEX REVERSAL; F-BOX PROTEIN; I-KAPPA-B; GLYCOGEN-SYNTHASE
KINASE-3; SYNOVIAL JOINT FORMATION; COLON-CARCINOMA CELLS; CRANIAL
NEURAL CREST; SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; CHONDROCYTE
DIFFERENTIATION
AB Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/beta-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/beta-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/beta-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote beta-catenin degradation, whereas the C terminus is required to inhibit beta-catenin transcriptional activity without affecting its stability. Sox9 binds to beta-catenin and components of the beta-catenin "destruction complex," glycogen synthase kinase 3 and beta-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance beta-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient beta-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by beta-catenin.
C1 [Topol, Lilia; Chen, Wen; Song, Hai; Day, Timothy F.; Yang, Yingzi] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Yang, YZ (reprint author), 49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
FU National Institutes of Health; NHGRI
FX This work was supported, in whole or in part, by the National Institutes
of Health, NHGRI intramural research program. The costs of publication
of this article were defrayed in part by the payment of page charges.
This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 61
TC 88
Z9 97
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 30
PY 2009
VL 284
IS 5
BP 3323
EP 3333
DI 10.1074/jbc.M808048200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 397ZL
UT WOS:000262700900075
PM 19047045
ER
PT J
AU Orr, SJ
Quigley, L
McVicar, DW
AF Orr, Selinda J.
Quigley, Laura
McVicar, Daniel W.
TI In vivo expression of signaling proteins in reconstituted NK cells
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Natural Killer cells; IL2R gamma(c); PI3K
ID RECEPTOR-GAMMA CHAIN; GENE-TRANSFER; PATHWAYS; MICE
AB Natural Killer cells are cells of the innate immune system that are important for the recognition and clearance of virally infected cells or tumors. Examination of the development and signaling of these cells has been severely hampered due to an inability to over-express proteins in these cells. We developed a novel technique to generate NK cells in vivo, all of which express a gene of interest. IL2R gamma(-/-)(c)/Rag2(-/-) mice do not develop NK cells due to the lack of IL15 signaling. We infected bone marrow from IL2R gamma(-/-)(c)/Rag2(-/-) mice with a retroviral construct encoding EGFP and IL2 gamma(c). connected by an IRES. NK cells selectively developed through expression of IL2R gamma(c) and 100% of these NK cells were found to be EGFP(+). In order to test the utilization of this method to examine the function of biologically relevant proteins, constitutively active PI3K p110 gamma and p110 delta isoforms were over-expressed in this system. Constitutively active p110 gamma revealed profound effects on NK cell development and function in vivo while p110 delta had little effect. Published by Elsevier B.V.
C1 [Orr, Selinda J.; Quigley, Laura; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Bldg 560,Rm 31-46, Frederick, MD 21702 USA.
EM mcvicard@mail.nih.gov
RI McVicar, Daniel/G-1970-2015;
OI Orr, Selinda/0000-0001-8539-7825
FU Intramural NIH HHS [Z99 CA999999, Z01 BC010300-10]
NR 12
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD JAN 30
PY 2009
VL 340
IS 2
BP 158
EP 163
DI 10.1016/j.jim.2008.10.014
PG 6
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 400LS
UT WOS:000262870100009
PM 19028500
ER
PT J
AU Lang, AE
Angel, M
Bhatia, K
Chen, R
Fahn, S
Hallett, M
Schrag, A
Thompson, P
AF Lang, Anthony E.
Angel, Michael
Bhatia, Kailash
Chen, Roberta
Fahn, Stanley
Hallett, Market
Schrag, Anette
Thompson, Philip
TI Myoclonus in Complex Regional Pain Syndrome
SO MOVEMENT DISORDERS
LA English
DT Letter
ID PSYCHOGENIC MOVEMENT-DISORDERS; REFLEX SYMPATHETIC DYSTROPHY;
GENERALIZED TONIC DYSTONIA; TRAUMA INDUCE DYSTONIA; FIXED DYSTONIA;
TREMOR
C1 [Lang, Anthony E.; Angel, Michael; Chen, Roberta] Univ Toronto, Div Neurol, Toronto, ON, Canada.
[Bhatia, Kailash] Sobell Dept Movement Neurosci, London, England.
[Fahn, Stanley] Neurol Inst, Dept Neurol, New York, NY 10032 USA.
[Hallett, Market] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Schrag, Anette] UCL, Inst Neurol Royal Free Campus, Dept Clin Neurosci, London, England.
[Thompson, Philip] Univ Adelaide, Univ Dept Med, Adelaide, SA, Australia.
[Thompson, Philip] Royal Adelaide Hosp, Dept Neurol, Adelaide, SA 5000, Australia.
RP Lang, AE (reprint author), Univ Toronto, Div Neurol, Toronto, ON, Canada.
EM lang@uhnres.utoronto.ca
RI Schrag, Anette/B-4181-2011; Chen, Robert/B-3899-2009
OI Schrag, Anette/0000-0002-9872-6680; Chen, Robert/0000-0002-8371-8629
NR 22
TC 10
Z9 10
U1 0
U2 0
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 JAN 30
PY 2009
VL 24
IS 2
BP 314
EP 316
DI 10.1002/mds.22355
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 401SO
UT WOS:000262962600031
PM 18973259
ER
PT J
AU Best, RB
Hummer, G
AF Best, Robert B.
Hummer, Gerhard
TI BIOCHEMISTRY Unfolding the Secrets of Calmodulin
SO SCIENCE
LA English
DT Editorial Material
ID C-TERMINAL DOMAIN; SINGLE PROTEIN; DYNAMICS; MOLECULE; BINDING
C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Hummer, Gerhard] NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016
OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543
FU Intramural NIH HHS [Z01 DK029033-08]
NR 16
TC 6
Z9 6
U1 1
U2 8
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 JAN 30
PY 2009
VL 323
IS 5914
BP 593
EP 594
DI 10.1126/science.1169555
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400JB
UT WOS:000262862800030
PM 19179519
ER
PT J
AU Venteicher, AS
Abreu, EB
Meng, ZJ
McCann, KE
Terns, RM
Veenstra, TD
Terns, MP
Artandi, SE
AF Venteicher, Andrew S.
Abreu, Eladio B.
Meng, Zhaojing
McCann, Kelly E.
Terns, Rebecca M.
Veenstra, Timothy D.
Terns, Michael P.
Artandi, Steven E.
TI A Human Telomerase Holoenzyme Protein Required for Cajal Body
Localization and Telomere Synthesis
SO SCIENCE
LA English
DT Article
ID SMALL NUCLEOLAR RNPS; DYSKERATOSIS-CONGENITA; RNA; ACCUMULATION;
HOMOLOG; BODIES; PURIFICATION; RECRUITMENT; BIOGENESIS; SHARE
AB Telomerase is a ribonucleoprotein ( RNP) complex that synthesizes telomere repeats in tissue progenitor cells and cancer cells. Active human telomerase consists of at least three principal subunits, including the telomerase reverse transcriptase, the telomerase RNA ( TERC), and dyskerin. Here, we identify a holoenzyme subunit, TCAB1 ( telomerase Cajal body protein 1), that is notably enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. TCAB1 associates with active telomerase enzyme, established telomerase components, and small Cajal body RNAs that are involved in modifying splicing RNAs. Depletion of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase- telomere association, and abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase trafficking and is required for telomere synthesis in human cancer cells.
C1 [Venteicher, Andrew S.; McCann, Kelly E.; Artandi, Steven E.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Venteicher, Andrew S.; Artandi, Steven E.] Stanford Univ, Sch Med, Program Biophys, Stanford, CA 94305 USA.
[Abreu, Eladio B.; Terns, Rebecca M.; Terns, Michael P.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
[Abreu, Eladio B.; Terns, Rebecca M.; Terns, Michael P.] Univ Georgia, Dept Genet, Athens, GA 30602 USA.
[Meng, Zhaojing; Veenstra, Timothy D.] NCI, Lab Proteom & Analyt Technol, Adv Technol Program, Sci Applicat Int Corp, Frederick, MD 21702 USA.
[McCann, Kelly E.; Artandi, Steven E.] Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA.
RP Artandi, SE (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM sartandi@stanford.edu
RI Terns, Michael/N-6435-2016
FU Medical Scientist Training Program [GM07365]; NCI [CA104676,
NO1-CO-12400, CA111691, CA125453]; Leukemia and Lymphoma Society
Specialized Centers of Research [7007-09]
FX This work was supported by Medical Scientist Training Program grant
GM07365 (A.S.V.) and NCI grant CA104676 (M.P.T. and R.M.T.), with a
Supplement to Promote Diversity in Health- Related Research (E.B.A.).
This project has been funded in part with federal funds from the NCI
under contract NO1-CO-12400 (T.D.V.). This work was supported by NCI
grants CA111691 and CA125453 (S.E.A.) and by Leukemia and Lymphoma
Society Specialized Centers of Research grant 7007-09 (S.E.A.).
NR 23
TC 236
Z9 252
U1 2
U2 18
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 JAN 30
PY 2009
VL 323
IS 5914
BP 644
EP 648
DI 10.1126/science.1165357
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 400JB
UT WOS:000262862800046
PM 19179534
ER
PT J
AU Langevin, SM
Lin, D
Matsuo, K
Gao, CM
Takezaki, T
Stolzenberg-Solomon, RZ
Vasavi, M
Hasan, Q
Taioli, E
AF Langevin, S. M.
Lin, D.
Matsuo, K.
Gao, C. M.
Takezaki, T.
Stolzenberg-Solomon, R. Z.
Vasavi, M.
Hasan, Q.
Taioli, E.
TI Review and pooled analysis of studies on MTHFR C677T polymorphism and
esophageal cancer
SO TOXICOLOGY LETTERS
LA English
DT Review
DE Methylenetetrahydrofolate reductase; Esophagus; Genetic epidemiology;
Case control studies
ID METHYLENETETRAHYDROFOLATE-REDUCTASE GENE; SQUAMOUS-CELL CARCINOMA;
5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; CHINESE POPULATION; DNA
METHYLATION; FOLATE STATUS; NEOADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER;
COMMON MUTATION; CARDIA CANCER
AB Esophageal cancer has been associated with tobacco and alcohol consumption, gastric reflux, exposure to nitrosamines from food or other environmental sources, and diets lacking folate. Susceptibility to esophageal cancer may be modified by functional polymorphisms in genes along the folate metabolic pathway, such as methylenetetrahydrofolate reductase (MTHFR). The C677T polymorphism is the most common functional variant, leading to a reduction in enzyme activity. We report a pooled analysis of 5 studies on the association of MTHFR C677T polymorphism and esophageal cancer, including 725 cases and 1531 controls. A significant association between the MTHFR 677 TT genotype and esophageal cancer was observed (OR = 2.63, 95% CI: 1.75-3.94), although there was significant heterogeneity between studies. A sensitivity analysis excluded one study: the association between 7 genotype and esophageal cancer was still present, although of reduced magnitude (OR = 1.57, 95% CI: 0.96-2.56). A significant interaction between smoking and TT genotype on esophageal cancer risk was observed, while no interaction was observed between alcohol consumption and genotype. (C) 2008 Published by Elsevier Ireland Ltd.
C1 [Langevin, S. M.; Taioli, E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Langevin, S. M.; Taioli, E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Lin, D.] Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China.
[Matsuo, K.] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
[Gao, C. M.] Jiangsu Prov Inst Canc Res, Dept Epidemiol, Nanjing, Peoples R China.
[Takezaki, T.] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Int Isl & Community Med, Kagoshima 890, Japan.
[Stolzenberg-Solomon, R. Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Vasavi, M.; Hasan, Q.] Kamineni Hosp, Dept Genet & Mol Med, Hyderabad, Andhra Pradesh, India.
[Hasan, Q.] Bhagwan Mahavir Med Res Ctr, Dept Genet, Hyderabad, Andhra Pradesh, India.
RP Taioli, E (reprint author), Suny Downstate Med Ctr, Grad Program Publ Hlth, SUNY Downstate Sch Publ Hlth, Dept Epidemiol & Biostat, 450 Clarkson Ave,Box 43, Brooklyn, NY 11203 USA.
EM emanuela.taioli@downstate.edu
OI Langevin, Scott/0000-0001-7031-1216; Matsuo, Keitaro/0000-0003-1761-6314
FU National Institutes of Health [P30CA047904-19S1]; NIH/NCI SPORE in Head
and Neck Cancer [5P50CA097190-02]
FX Environmental Cancer Risk, Nutrition and Individual Susceptibility
(ECNIS); the authors thank Barbara M. Stadterman, GSEC administrator,
for her support (National Institutes of Health grant P30CA047904-19S1;
NIH/NCI SPORE in Head and Neck Cancer 5P50CA097190-02).
NR 64
TC 34
Z9 37
U1 0
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JAN 30
PY 2009
VL 184
IS 2
BP 73
EP 80
DI 10.1016/j.toxlet.2008.09.003
PG 8
WC Toxicology
SC Toxicology
GA 405JU
UT WOS:000263219900001
PM 18840514
ER
PT J
AU Yuditskaya, S
Tumblin, A
Hoehn, GT
Wang, GH
Drake, SK
Xu, XL
Ying, SX
Chi, AH
Remaley, AT
Shen, RF
Munson, PJ
Suffredini, AF
Kato, GJ
AF Yuditskaya, Susan
Tumblin, Ashaunta
Hoehn, Gerard T.
Wang, Guanghui
Drake, Steven K.
Xu, Xiuli
Ying, Saixia
Chi, Amy H.
Remaley, Alan T.
Shen, Rong-Fong
Munson, Peter J.
Suffredini, Anthony F.
Kato, Gregory J.
TI Proteomic identification of altered apolipoprotein patterns in pulmonary
hypertension and vasculopathy of sickle cell disease
SO BLOOD
LA English
DT Article
ID NITRIC-OXIDE BIOAVAILABILITY; SERUM AMYLOID-A; VASCULAR FUNCTION; FREE
HEMOGLOBIN; LUNG-DISEASE; RISK; ACTIVATION; CHILDREN; PLASMA; ANEMIA
AB Pulmonary arterial hypertension (PAH) is emerging as a major complication and independent risk factor for death among adults with sickle cell disease (SCD). Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), we searched for biomarkers of PAH in plasma specimens from 27 homozygous sickle cell anemia (HbSS) patients with PAH and 28 without PAH. In PAH patients, analysis consistently showed lower abundance of a 28.1-kDa peak (P <.001), identified by high-resolution mass spectrometry as the oxidant-scavenging protein apolipoprotein A-I (apoA-I), which correlated with clinical assays of apoA-I (r = .58, P <.001) and high-density lipoprotein (HDL) levels (r = .50, P = .001). Consistent with endothelial dysfunction that may mediate this effect in PAH, HbSS patients with lower apoA-I levels also displayed impaired vasodilatory responses to acetylcholine (mean +/- SEM, 189% +/- 34% [n = 13] vs 339% +/- 51% [n = 13], P <.001). As a group, patients with SCD demonstrated significantly lower apoA-I levels than African-American control subjects. The PAH cohort was further characterized by high levels of apolipoproteins A-II and B and serum amyloid A, and low levels of haptoglobin dimers and plasminogen. These results imply a relationship of apolipoproteins to the development of PAH vasculopathy in SCD, potentially involving an unexpected mechanistic parallel to atherosclerosis, another proliferative vasculopathy. (Blood. 2009;113:1122-1128)
C1 [Yuditskaya, Susan; Tumblin, Ashaunta; Xu, Xiuli; Chi, Amy H.; Remaley, Alan T.; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Hoehn, Gerard T.; Wang, Guanghui; Drake, Steven K.; Suffredini, Anthony F.; Kato, Gregory J.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Ying, Saixia; Munson, Peter J.] NHLBI, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA.
[Shen, Rong-Fong] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Institutes of Health (NIH); Clinical Research Training Program
(CRTP); Pfizer Pharmaceuticals Group (NewYork, NY)
FX This research was supported by intramural research funds from the
National Institutes of Health (NIH). S. Y. andA. T. were supported by
the Clinical Research Training Program (CRTP), a public-private
partnership supported jointly by the NIH and a grant to the Foundation
for the NIH from Pfizer Pharmaceuticals Group (NewYork, NY).
NR 49
TC 38
Z9 39
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 JAN 29
PY 2009
VL 113
IS 5
BP 1122
EP 1128
DI 10.1182/blood-2008-03-142604
PG 7
WC Hematology
SC Hematology
GA 400RD
UT WOS:000262885300020
PM 19023114
ER
PT J
AU Rizzo, JD
Curtis, RE
Socie, G
Sobocinski, KA
Gilbert, E
Landgren, O
Travis, LB
Travis, WD
Flowers, MED
Friedman, DL
Horowitz, MM
Wingard, JR
Deeg, HJ
AF Rizzo, J. Douglas
Curtis, Rochelle E.
Socie, Gerard
Sobocinski, Kathleen A.
Gilbert, Ethel
Landgren, Ola
Travis, Lois B.
Travis, William D.
Flowers, Mary E. D.
Friedman, Debra L.
Horowitz, Mary M.
Wingard, John R.
Deeg, H. Joachim
TI Solid cancers after allogeneic hematopoietic cell transplantation
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM
SURVIVORS; 2ND MALIGNANT NEOPLASMS; CHILDHOOD-CANCER; BREAST-CANCER;
THYROID-CANCER; WORKING PARTY; RISK-FACTORS; CHILDREN
AB Transplant recipients have been reported to have an increased risk of solid cancers but most studies are small and have limited ability to evaluate the interaction of host, disease, and treatment-related factors. In the largest study to date to evaluate risk factors for solid cancers, we studied a multi-institutional cohort of 28 874 allogeneic transplant recipients with 189 solid malignancies. Overall, patients developed new solid cancers at twice the rate expected based on general population rates (observed-to-expected ratio 2.1; 95% confidence interval 1.8-2.5), with the risk increasing over time (P trend <.001); the risk reached 3-fold among patients followed for 15 years or more after transplantation. New findings showed that the risk of developing a non-squamous cell carcinoma (non-SCC) following conditioning radiation was highly dependent on age at exposure. Among patients irradiated at ages under 30 years, the relative risk of non-SCC was 9 times that of nonirradiated patients, while the comparable risk for older patients was 1.1 (P interaction <.01). Chronic graft-versus-host disease and male sex were the main determinants for risk of SCC. These data indicate that allogeneic transplant survivors, particularly those irradiated at young ages, face increased risks of solid cancers, supporting strategies to promote lifelong surveillance among these patients. (Blood. 2009; 113:1175-1183)
C1 [Rizzo, J. Douglas; Sobocinski, Kathleen A.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI 53226 USA.
[Curtis, Rochelle E.; Gilbert, Ethel; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Socie, Gerard] Hop St Louis, Paris, France.
[Travis, Lois B.] James P Willmot Canc Ctr, Rochester, NY USA.
[Travis, William D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Flowers, Mary E. D.; Friedman, Debra L.; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Wingard, John R.] Univ Florida, Shands Hosp, Gainesville, FL USA.
RP Rizzo, JD (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM rizzo@mcw.edu
FU NCI NIH HHS [U24-CA76518, U24 CA076518]; NHLBI NIH HHS [5U01HL069294,
U01 HL069294]; PHS HHS [HHSH234200637015C]
NR 43
TC 163
Z9 167
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JAN 29
PY 2009
VL 113
IS 5
BP 1175
EP 1183
DI 10.1182/blood-2008-05-158782
PG 9
WC Hematology
SC Hematology
GA 400RD
UT WOS:000262885300026
PM 18971419
ER
PT J
AU Chun, CZ
Kaur, S
Samant, GV
Wang, L
Pramanik, K
Garnaas, MK
Li, KG
Field, L
Mukhopadhyay, D
Ramchandran, R
AF Chun, Chang Z.
Kaur, Sukhbir
Samant, Ganesh V.
Wang, Ling
Pramanik, Kallal
Garnaas, Maija K.
Li, Keguo
Field, Lyndsay
Mukhopadhyay, Debabrata
Ramchandran, Ramani
TI Snrk-1 is involved in multiple steps of angioblast development and acts
via notch signaling pathway in artery-vein specification in vertebrates
SO BLOOD
LA English
DT Article
ID EMBRYONIC VASCULAR DEVELOPMENT; ENDOTHELIAL-CELLS; ZEBRAFISH;
OVEREXPRESSION; VASCULOGENESIS; MALFORMATIONS; ANGIOGENESIS; EXPRESSION;
GRIDLOCK; PROTEIN
AB In vertebrates, molecular mechanisms dictate angioblasts' migration and subsequent differentiation into arteries and veins. In this study, we used a microarray screen to identify a novel member of the sucrose nonfermenting related kinase (snrk-1) family of serine/threonine kinases expressed specifically in the embryonic zebrafish vasculature and investigated its function in vivo. Using gain- and loss-of-function studies in vivo, we show that Snrk-1 plays an essential role in the migration, maintenance, and differentiation of angioblasts. The kinase function of Snrk-1 is critical for migration and maintenance, but not for the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells show only defects in migration. The snrk-1 gene acts down-stream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function. (Blood. 2009; 113: 1192-1199)
C1 [Chun, Chang Z.; Samant, Ganesh V.; Pramanik, Kallal; Garnaas, Maija K.; Li, Keguo; Ramchandran, Ramani] Med Coll Wisconsin, Dept Pediat, Translat & Biomed Res Ctr, CRI Dev Vasc Biol Program, Milwaukee, WI 53226 USA.
[Kaur, Sukhbir] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Wang, Ling; Mukhopadhyay, Debabrata] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN USA.
[Field, Lyndsay] Univ Massachusetts Dartmouth, N Dartmouth, MA USA.
RP Ramchandran, R (reprint author), Med Coll Wisconsin, Dept Pediat, Translat & Biomed Res Ctr, CRI Dev Vasc Biol Program, CRI C3420,8701Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA.
EM rramchan@mcw.edu
FU National Institutes of Health [HL072178, HL70567]; Medical College of
Wisconsin, Milwaukee
FX This study was supported in part by research funding from National
Institutes of Health (NIH, Bethesda, MD) grants HL072178 and HL70567
(D.M.) and by seed funds from the Children's Research Institute at the
Medical College of Wisconsin, Milwaukee (R.R.). R. R. is a recipient of
the National Cancer Institute (NCI, Bethesda, MD) Scholar Award. G. S.
is a recipient of the State of Wisconsin Breast Cancer Research Tax
Write-off Program Award. L. W. is a fellow of American Heart Association
(Washington, DC).
NR 23
TC 15
Z9 15
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JAN 29
PY 2009
VL 113
IS 5
BP 1192
EP 1199
DI 10.1182/blood-2008-06-162156
PG 8
WC Hematology
SC Hematology
GA 400RD
UT WOS:000262885300028
PM 18723694
ER
PT J
AU Calvo, E
Pham, VM
Marinotti, O
Andersen, JF
Ribeiro, JMC
AF Calvo, Eric
Pham, Van M.
Marinotti, Osvaldo
Andersen, John F.
Ribeiro, Jose M. C.
TI The salivary gland transcriptome of the neotropical malaria vector
Anopheles darlingi reveals accelerated evolution of genes relevant to
hematophagy
SO BMC GENOMICS
LA English
DT Review
ID ADULT FEMALE MOSQUITO; PLATELET-AGGREGATION INHIBITOR; LEECH
HIRUDO-MEDICINALIS; RICH SECRETORY PROTEINS; AEDES-AEGYPTI;
TRIATOMA-INFESTANS; LUTZOMYIA-LONGIPALPIS; STEPHENSI MOSQUITO; SEQUENCE
ALIGNMENT; ANTIBODY-RESPONSE
AB Background: Mosquito saliva, consisting of a mixture of dozens of proteins affecting vertebrate hemostasis and having sugar digestive and antimicrobial properties, helps both blood and sugar meal feeding. Culicine and anopheline mosquitoes diverged similar to 150 MYA, and within the anophelines, the New World species diverged from those of the Old World similar to 95 MYA. While the sialotranscriptome (from the Greek sialo, saliva) of several species of the Cellia subgenus of Anopheles has been described thoroughly, no detailed analysis of any New World anopheline has been done to date. Here we present and analyze data from a comprehensive salivary gland (SG) transcriptome of the neotropical malaria vector Anopheles darlingi (subgenus Nyssorhynchus).
Results: A total of 2,371 clones randomly selected from an adult female An. darlingi SG cDNA library were sequenced and used to assemble a database that yielded 966 clusters of related sequences, 739 of which were singletons. Primer extension experiments were performed in selected clones to further extend sequence coverage, allowing for the identification of 183 protein sequences, 114 of which code for putative secreted proteins.
Conclusion: Comparative analysis of sialotranscriptomes of An. darlingi and An. gambiae reveals significant divergence of salivary proteins. On average, salivary proteins are only 53% identical, while housekeeping proteins are 86% identical between the two species. Furthermore, An. darlingi proteins were found that match culicine but not anopheline proteins, indicating loss or rapid evolution of these proteins in the old world Cellia subgenus. On the other hand, several well represented salivary protein families in old world anophelines are not expressed in An. darlingi.
C1 [Calvo, Eric; Pham, Van M.; Andersen, John F.; Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Marinotti, Osvaldo] Univ Calif Irvine, Dept Biochem & Mol Biol, Irvine, CA 92697 USA.
RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM eric.calvo@fda.hhs.gov; vpham@niaid.nih.gov; omarinot@uci.edu;
jandersen@niaid.nih.gov; jribeiro@niaid.nih.gov
OI Marinotti, Osvaldo/0000-0002-7173-7160; Calvo, Eric/0000-0001-7880-2730;
Ribeiro, Jose/0000-0002-9107-0818
FU Intramural Research Program of the 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 Dr. Bruno
Arca for valuable discussions, and NIAID intramural editor Brenda Rae
Marshall for assistance.
NR 158
TC 47
Z9 51
U1 2
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JAN 29
PY 2009
VL 10
AR 57
DI 10.1186/1471-2164-10-57
PG 27
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 418BP
UT WOS:000264122500003
PM 19178717
ER
PT J
AU Mullighan, CG
Su, XP
Zhang, JH
Radtke, I
Phillips, LAA
Miller, CB
Ma, J
Liu, W
Cheng, C
Schulman, BA
Harvey, RC
Chen, I
Clifford, RJ
Carroll, WL
Reaman, G
Bowman, WP
Devidas, M
Gerhard, DS
Yang, WJ
Relling, MV
Shurtleff, SA
Campana, D
Borowitz, MJ
Pui, C
Smith, M
Hunger, SP
Willman, CL
Downing, JR
AF Mullighan, Charles G.
Su, Xiaoping
Zhang, Jinghui
Radtke, Ina
Phillips, Letha A. A.
Miller, Christopher B.
Ma, Jing
Liu, Wei
Cheng, Cheng
Schulman, Brenda A.
Harvey, Richard C.
Chen, I-Ming
Clifford, Robert J.
Carroll, William L.
Reaman, Gregory
Bowman, W. Paul
Devidas, Meenakshi
Gerhard, Daniela S.
Yang, Wenjian
Relling, Mary V.
Shurtleff, Sheila A.
Campana, Dario
Borowitz, Michael J.
Pui, Ching-Hon
Smith, Malcolm
Hunger, Stephen P.
Willman, Cheryl L.
Downing, James R.
CA Childrens Oncology Grp
TI Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MINIMAL RESIDUAL DISEASE; TOTAL THERAPY; IKAROS GENE; CHILDHOOD;
CHILDREN; EXPRESSION; TRANSCRIPTION; MICROARRAY; LINEAGE; CELLS
AB Background: Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined.
Methods: We studied a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1-positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell-progenitor ALL.
Results: More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients in the original cohort); PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Using copy-number abnormalities, we identified a predictor of poor outcome that was validated in the independent validation cohort. This predictor was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS. The gene-expression signature of the group of patients with a poor outcome revealed increased expression of hematopoietic stem-cell genes and reduced expression of B-cell-lineage genes, and it was similar to the signature of BCR-ABL1-positive ALL, another high-risk subtype of ALL with a high frequency of IKZF1 deletion.
Conclusions: Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell-progenitor ALL.
N Engl J Med 2009;360:470-80.
C1 [Mullighan, Charles G.; Su, Xiaoping; Radtke, Ina; Phillips, Letha A. A.; Miller, Christopher B.; Shurtleff, Sheila A.; Campana, Dario; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
[Liu, Wei; Cheng, Cheng] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA.
[Yang, Wenjian; Relling, Mary V.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Schulman, Brenda A.] St Jude Childrens Hosp, Dept Biol Struct, Memphis, TN 38105 USA.
[Campana, Dario; Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Clifford, Robert J.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA.
[Smith, Malcolm] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Schulman, Brenda A.] Johns Hopkins Med Inst, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Borowitz, Michael J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Harvey, Richard C.; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA.
[Carroll, William L.] NYU, Inst Canc, New York, NY USA.
[Reaman, Gregory] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Bowman, W. Paul] Cook Childrens Med Ctr, Dept Hematol & Oncol, Ft Worth, TX USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA.
[Devidas, Meenakshi] Childrens Oncol Grp, Gainesville, FL USA.
[Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA.
RP Downing, JR (reprint author), St Jude Childrens Hosp, Dept Pathol, 262 Danny Thomas Pl,MS 271, Memphis, TN 38105 USA.
EM james.downing@stjude.org
OI Mullighan, Charles/0000-0002-1871-1850
FU Children's Oncology Group Chair's Award [CA098543]; Strategic Partnering
to Evaluate Cancer Signatures Program [CA114762]; National Cancer
Institute; National Institute of General Medical Sciences
Pharmacogenetics Research Network and Database [U01 GM61393,
U01GM61374]; Cancer Center [21765]; National Institutes of Health [R01
CA86011, N01-C0-12400]; Leukemia and Lymphoma Society Specialized Center
of Research [7388-06]; CureSearch National Childhood Cancer Foundation;
National Health and Medical Research Council (Australia); Australia) C.
J. Martin Traveling Fellowship; American Lebanese Syrian Associated
Charities of St. Jude Children's Research Hospital; NCI; Becton
Dickinson Biosciences; Xanthus Pharmaceuticals
FX We thank Zhongling Cai and Claire Boltz for technical assistance and
Stephen Smale for helpful discussions.
NR 34
TC 531
Z9 560
U1 2
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 JAN 29
PY 2009
VL 360
IS 5
BP 470
EP 480
DI 10.1056/NEJMoa0808253
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 399PS
UT WOS:000262812400006
PM 19129520
ER
PT J
AU Subak, LL
Wing, R
West, DS
Franklin, F
Vittinghoff, E
Creasman, JM
Richter, HE
Myers, D
Burgio, KL
Gorin, AA
Macer, J
Kusek, JW
Grady, D
AF Subak, Leslee L.
Wing, Rena
West, Delia Smith
Franklin, Frank
Vittinghoff, Eric
Creasman, Jennifer M.
Richter, Holly E.
Myers, Deborah
Burgio, Kathryn L.
Gorin, Amy A.
Macer, Judith
Kusek, John W.
Grady, Deborah
CA PRIDE Investigators
TI Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-AGED WOMEN;
CARDIOVASCULAR-DISEASE; STRESS-INCONTINENCE; STYLE INTERVENTION;
RISK-FACTORS; FOLLOW-UP; SURGERY; HEALTH
AB Background: Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking.
Methods: We randomly assigned 338 overweight and obese women with at least 10 urinary-incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients).
Results: The mean (+/-SD) age of the participants was 53+/-11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36+/-6 and 36+/-5, respectively; incontinence episodes, 24+/-18 and 24+/-16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P=0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress-incontinence episodes (P=0.02), but not of urge-incontinence episodes (P=0.14). A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P=0.009), and urge-incontinence episodes (P=0.04).
Conclusions: A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. (ClinicalTrials.gov number, NCT00091988.)
N Engl J Med 2009;360:481-90.
C1 [Subak, Leslee L.; Vittinghoff, Eric; Creasman, Jennifer M.; Macer, Judith; Grady, Deborah] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA.
[Wing, Rena] Miriam Hosp, Providence, RI 02906 USA.
[Wing, Rena; Myers, Deborah] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[West, Delia Smith] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA.
[Franklin, Frank; Richter, Holly E.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL USA.
[Burgio, Kathryn L.] Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA.
[Gorin, Amy A.] Univ Connecticut, Storrs, CT USA.
[Kusek, John W.] NIDDKD, Bethesda, MD 20892 USA.
[Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Subak, LL (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA.
EM subakl@obgyn.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK067860, U01 DK067861, U01 DK067862]; Office of Research on Women's
Health; Pfizer; Bionovo; Astellas; GlaxoSmithKline
FX Supported by grants from the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) (U01 DK067860, U01 DK067861, and
U01 DK067862) and from the Office of Research on Women's Health.; Dr.
Subak reports serving on an advisory board for Pfizer and receiving
grant support from Pfizer; Dr. Grady, receiving grant support from
Bionovo; Dr. Kusek, owning stock in Eli Lilly, Pfizer, and deCODE
Genetics; and Dr. Burgio, serving on an advisory board for Pfizer,
receiving grant support from Pfizer, and receiving advisory-board fees
from Astellas and GlaxoSmithKline. No other potential conflict of
interest relevant to this article was reported.; The views expressed are
those of the authors and do not necessarily represent the official views
of the NIDDK or the National Institutes of Health.
NR 36
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U1 1
U2 11
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 JAN 29
PY 2009
VL 360
IS 5
BP 481
EP 490
DI 10.1056/NEJMoa0806375
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 399PS
UT WOS:000262812400007
PM 19179316
ER
PT J
AU Kohn, DB
Candotti, F
AF Kohn, Donald B.
Candotti, Fabio
TI Gene Therapy Fulfilling Its Promise.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW; DISEASE; VECTOR; CELLS;
TRANSPLANTATION; GENOTOXICITY
C1 [Kohn, Donald B.] Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90027 USA.
[Kohn, Donald B.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA.
[Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Kohn, DB (reprint author), Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90027 USA.
RI Kohn, Donald/N-5085-2016
OI Kohn, Donald/0000-0003-1840-6087
NR 16
TC 61
Z9 62
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 JAN 29
PY 2009
VL 360
IS 5
BP 518
EP 521
DI 10.1056/NEJMe0809614
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 399PS
UT WOS:000262812400014
PM 19179320
ER
PT J
AU Ping, PP
AF Ping, Peipei
TI Getting to the Heart of Proteomics.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, NHLBI, Program Project Myocardial Ischemia Injury & Prot, Los Angeles, CA 90095 USA.
RP Ping, PP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, NHLBI, Program Project Myocardial Ischemia Injury & Prot, Los Angeles, CA 90095 USA.
FU NHLBI NIH HHS [R37 HL063901, P01 HL080111-04, P01 HL080111, R01
HL101228]
NR 5
TC 19
Z9 19
U1 0
U2 4
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 JAN 29
PY 2009
VL 360
IS 5
BP 532
EP 534
DI 10.1056/NEJMcibr0808487
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 399PS
UT WOS:000262812400018
PM 19179323
ER
PT J
AU Guigon, CJ
Zhao, L
Willingham, MC
Cheng, SY
AF Guigon, C. J.
Zhao, L.
Willingham, M. C.
Cheng, S-Y
TI PTEN deficiency accelerates tumour progression in a mouse model of
thyroid cancer
SO ONCOGENE
LA English
DT Article
DE thyroid cancer; Pten; carcinogenesis; mouse model; mutations
ID PROTEIN-KINASE-B; COWDEN-DISEASE; GERMLINE MUTATIONS; PHOSPHOINOSITIDE
3-KINASE; TRANSCRIPTION FACTORS; SUPPRESSOR GENE; LIGAND-BINDING;
BETA-RECEPTOR; HORMONE; RESISTANCE
AB Inactivation and silencing of PTEN have been observed in multiple cancers, including follicular thyroid carcinoma. PTEN (phosphatase and tensin homologue deleted from chromosome 10) functions as a tumour suppressor by opposing the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. Despite correlative data, how deregulated PTEN signalling leads to thyroid carcinogenesis is not known. Mice harbouring a dominant-negative mutant thyroid hormone receptor beta (TR beta(PV/PV) mice) spontaneously develop follicular thyroid carcinoma and distant metastases similar to human cancer. To elucidate the role of PTEN in thyroid carcinogenesis, we generated TR beta(PV/PV) mice haploinsufficient for Pten (TR beta(PV/PV)Pten(+/-) mouse). PTEN deficiency accelerated the progression of thyroid tumour and increased the occurrence of metastasis spread to the lung in TR beta(PV/PV)Pten(+/-) mice, thereby significantly reducing their survival as compared with TR beta(PV/PV)Pten(+/+) mice. AKT activation was further increased by two-fold in TR beta(PV/PV)Pten(+/-) mice thyroids, leading to increased activity of the downstream mammalian target of rapamycin (mTOR)-p70S6K signalling and decreased activity of the forkhead family member FOXO3a. Consistently, cyclin D1 expression was increased. Apoptosis was decreased as indicated by increased expression of nuclear factor-kappa B (NF-kappa B) and decreased caspase-3 activity in the thyroids of TR beta(PV/PV)Pten(+/-) mice. Our results indicate that PTEN deficiency resulted in increased cell proliferation and survival in the thyroids of TR beta(PV/PV)Pten(+/-) mice. Altogether, our study provides direct evidence to indicate that in vivo, PTEN is a critical regulator in the follicular thyroid cancer progression and invasiveness.
C1 [Cheng, S-Y] NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA.
RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute; National
Institutes of Health
FX ;We thank Dr Hao Ying for assistance in the determination of thyroid
function tests. This research was supported by the Intramural Research
Program of Center for Cancer Research, National Cancer Institute,
National Institutes of Health.
NR 37
TC 48
Z9 48
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN 29
PY 2009
VL 28
IS 4
BP 509
EP 517
DI 10.1038/onc.2008.407
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 400KM
UT WOS:000262866500005
PM 18997818
ER
PT J
AU Kitagaki, J
Yang, Y
Saavedra, JE
Colburn, NH
Keefer, LK
Perantoni, AO
AF Kitagaki, J.
Yang, Y.
Saavedra, J. E.
Colburn, N. H.
Keefer, L. K.
Perantoni, A. O.
TI Nitric oxide prodrug JS-K inhibits ubiquitin E1 and kills tumor cells
retaining wild-type p53
SO ONCOGENE
LA English
DT Article
DE JS-K; nitric oxide (NO); ubiquitin; tumor; apoptosis; p53
ID IN-VITRO; BETA-CATENIN; APOPTOSIS; CANCER; DESTRUCTION; TRANSLATION;
GLUTATHIONE; PATHWAYS; SYSTEM; GROWTH
AB Nitric oxide (NO) is a major effector molecule in cancer prevention. A number of studies have shown that NO prodrug JS-K (O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxy-carbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate) induces apoptotic cell death in vitro and in vivo, indicating that it is a promising new therapeutic for cancer. However, the mechanism of its tumor-killing activity remains unclear. Ubiquitin plays an important role in the regulation of tumorigenesis and cell apoptosis. Our earlier report has shown that inactivation of the ubiquitin system through blocking E1(ubiquitin-activating enzyme) activity preferentially induces apoptosis in p53-expressing transformed cells. As E1 has an active cysteine residue that could potentially interact with NO, we hypothesized that JS-K could inactivate E1 activity. E1 activity was evaluated by detecting ubiquitin-E1 conjugates through immunoblotting. JS-K strikingly inhibits the ubiquitin-E1 thioester formation in cells in a dose-dependent manner with an IC(50) of approximately 2 mu M, whereas a JS-K analog that cannot release NO did not affect these levels in cells. Moreover, JS-K decreases total ubiquitylated proteins and increases p53 levels, which is mainly regulated by ubiquitin and proteasomal degradation. Furthermore, JS-K preferentially induces cell apoptosis in p53-expressing transformed cells. These findings indicate that JS-K inhibits E1 activity and kills transformed cells harboring wild-type p53.
C1 [Kitagaki, J.; Yang, Y.; Perantoni, A. O.] Natl Canc Inst Frederick, Canc & Dev Biol Lab, Ctr Canc Res, Natl Inst Hlth, Frederick, MD 21702 USA.
[Saavedra, J. E.] Natl Canc Inst Frederick, Basic Res Program, SAIC Frederick, Ctr Canc Res,Natl Inst Hlth, Frederick, MD 21702 USA.
[Colburn, N. H.] Natl Canc Inst Frederick, Lab Canc Prevent, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Keefer, L. K.] Natl Canc Inst Frederick, Comparat Carcinogenesis Lab, Ctr Canc Res, Natl Inst Hlth, Frederick, MD 21702 USA.
RP Perantoni, AO (reprint author), Natl Canc Inst Frederick, Canc & Dev Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bldg 538,Rm 221,1050 Boyles St, Frederick, MD 21702 USA.
EM yangyili@ncifcrf.gov; peranton@ncifcrf.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU NIH; National Cancer Institute; Center for Cancer Research; National
Cancer Institute [NOI-CO-12400]
FX We are grateful to the NIH Fellows Editorial Board for revisions of this
paper. This work was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and by
National Cancer Institute Contract No. NOI-CO-12400 to SAIC Inc. JK was
a fellow of the Japanese Society for the Promotion of Science.
NR 26
TC 26
Z9 27
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN 29
PY 2009
VL 28
IS 4
BP 619
EP 624
DI 10.1038/onc.2008.401
PG 6
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 400KM
UT WOS:000262866500015
PM 18978812
ER
PT J
AU Lee, CH
Kuo, WC
Beri, S
Kapre, S
Joshi, JS
Bouveret, N
LaForce, FM
Frasch, CE
AF Lee, Che-Hung
Kuo, Wen-Chun
Beri, Suresh
Kapre, Subash
Joshi, Jayant S.
Bouveret, Nancy
LaForce, F. Marc
Frasch, Carl E.
TI Preparation and characterization of an immunogenic meningococcal group A
conjugate vaccine for use in Africa
SO VACCINE
LA English
DT Article
DE Vaccine; Conjugate; Polysaccharide
ID NEISSERIA-MENINGITIDIS SEROGROUP; SUB-SAHARAN AFRICA; CAPSULAR
POLYSACCHARIDE; O-ACETYLATION; GROUP-B; ANTIBODY; IMMUNIZATION;
PERSISTENCE; PREVENTION; EPIDEMIC
AB Periodic epidemics of group A meningococcal (Mn A) meningitis continue to occur in sub-Saharan Africa. For its prevention, a Mn A polysaccharide (PS)-tetanus toxoid (TT) conjugate vaccine was developed using reductive amination of polysaccharicle aldehydes and toxoid hydrazides. In mouse immunization studies, a schedule of three bi-weekly s.c. immunizations of 0.1 or 1 mu g of the conjugate (PS content) without an adjuvant induced serum antibody levels of >10,000 units/mL measured by enzyme-linked immunosorbent assay (ELISA) as compared to similar to 100 units/mL in PS control mice. The elicited antibodies were active in bactericidal assays using either baby rabbit or human complement (titers >1500 compared to similar to 200 for the PS control group). The synthesis process is reproducible and scalable, and has been successfully used for manufacturing a Mn A PS-TT conjugate vaccine based on a paradigm of shared manufacturing with transfer of new technology [Jodar L, LaForce FM, Ceccarini C, Aguado T, Granoff DM. Meningococcal conjugate vaccine for Africa: a model for development of new vaccine for the poorest countries. Lancet 2003, 361:1092-4]. A phase 1 clinical trial of the manufactured Men A-TT conjugate vaccine has been successfully carried out in adults in India, and a phase 2 clinical trial in young children is currently underway in Africa. Published by Elsevier Ltd.
C1 [Frasch, Carl E.] US FDA, Lab Bacterial Polysaccharides, HFM 428, DBPAP,OVRR,CBER,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Beri, Suresh; Kapre, Subash; Joshi, Jayant S.] Serum Inst India Ltd, Pune, Maharashtra, India.
[Bouveret, Nancy; LaForce, F. Marc] Meningitis Vaccine Project, Ferney Voltaire, France.
RP Lee, CH (reprint author), US FDA, Lab Bacterial Polysaccharides, HFM 428, DBPAP,OVRR,CBER,Ctr Biol Evaluat & Res, NIH Campus,Bldg 29,Room 404,29 Lincoln Ave, Bethesda, MD 20892 USA.
EM robert.lee@fda.hhs.gov
FU CRADA
FX The authors are grateful to Dr. Dan Granoff and his laboratory for
performing bactericidal assay with human complement. We thank Ms.
Britany Bowen for her technical support, Mr. Scot Noris for recording
the NMR spectra of native and activated Mn A PS, and Drs. Margaret Bash,
Chao-Ming Tsai and Willie Vann for their review and comments of this
manuscript. This research is supported in part by a CRADA between CBER
and PATH.
NR 35
TC 39
Z9 43
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 29
PY 2009
VL 27
IS 5
BP 726
EP 732
DI 10.1016/j.vaccine.2008.11.065
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 405II
UT WOS:000263216100019
PM 19063929
ER
PT J
AU Demeter, LM
Jiang, H
Mukherjee, AL
Morse, GD
DiFrancesco, R
DiCenzo, R
Dykes, C
Sista, P
Bacheler, L
Klingman, K
Rinehart, A
Albrecht, M
AF Demeter, Lisa M.
Jiang, Hongyu
Mukherjee, A. Lisa
Morse, Gene D.
DiFrancesco, Robin
DiCenzo, Robert
Dykes, Carrie
Sista, Prakash
Bacheler, Lee
Klingman, Karin
Rinehart, Alex
Albrecht, Mary
TI A randomized trial of therapeutic drug monitoring of protease inhibitors
in antiretroviral-experienced, HIV-1-infected patients
SO AIDS
LA English
DT Article; Proceedings Paper
CT 15th Conference on Retroviruses and Opportunistic Infections
CY FEB 03-06, 2008
CL Boston, MA
DE antiretroviral therapy; clinical trials; HIV drug resistance;
pharmacokinetics; protease inhibitors; therapeutic drug monitoring
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEAVILY PRETREATED PATIENTS; HIV-INFECTED
PATIENTS; VIROLOGICAL RESPONSE; LOPINAVIR-RITONAVIR; SUSCEPTIBILITY
SCORES; QUOTIENT; AMPRENAVIR; RESISTANCE; PHARMACOKINETICS
AB Objective: Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV-infected patients is controversial. We evaluated this strategy in a randomized, open-label clinical trial, using a normalized inhibitory quotient (NIQ), which incorporates drug exposure and viral drug resistance. NIQs <= 1 may predict poor outcome and identify patients who could benefit from dose escalation.
Design/methods: Eligible patients had a viral load >1000 copies/ml on a failing regimen, and began a new protease inhibitor containing regimen at entry. All FDA-approved protease inhibitors available during the study recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three participants with NIQ <= 1, oil the basis of their week 2 protease inhibitor trough concentration and pre-entry drug resistance test, were randomized at week 4 to standard of care (SOC) or protease inhibitor dose escalation (TDM). The primary endpoint was change in log(10) plasma HIV-1 RNA concentration from randomization to 20 weeks later.
Results: Ninety-one patients were randomized to SOC and 92 to TDM. NIQs increased more in the TDM arm compared to SOC (+69 versus +25%, P=0.01). Despite this, TDM and SOC arms showed no difference in Outcome (+0.09 versus +0.02 log(10), P=0.17). In retrospective Subgroup analyses, patients with less HIV resistance to their protease inhibitors benefited from TDM (P=0.002), as did black and Hispanic patients (P=0.035 and 0.05, respectively). Differences between black and white patients persisted when accounting for protease inhibitor susceptibility.
Conclusions: There was no overall benefit of TDM. In post hoc subgroup analyses, TDM appeared beneficial in black and Hispanic patients, and in patients whose virus retained some susceptibility to the protease inhibitors in their regimen. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Demeter, Lisa M.; DiCenzo, Robert; Dykes, Carrie] Univ Rochester, Sch Med & Dent, Div Infect Dis, Rochester, NY USA.
[Jiang, Hongyu; Mukherjee, A. Lisa] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Morse, Gene D.; DiFrancesco, Robin; DiCenzo, Robert] SUNY Buffalo, Dept Pharm Practice, Buffalo, NY USA.
[Sista, Prakash; Bacheler, Lee] VircoLab Inc, Durham, NC USA.
[Albrecht, Mary] Beth Israel Deaconess Med Ctr, Div Infect Dis, Bethesda, MD USA.
[Klingman, Karin] NIH, Div Aids, Bethesda, MD 20892 USA.
[Rinehart, Alex] Tibotec Therapeut, Bridgewater, NJ USA.
RP Demeter, LM (reprint author), 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA.
EM lisa_demeter@urmc.rochester.edu
FU NCRR NIH HHS [M01 RR000032, M01 RR000044, M01 RR000044-440787, M01
RR000047, M01 RR000051, M01 RR000096, RR-00032, RR-00044, RR-00047,
RR-00051, RR-00075, RR-00096]; NIAID NIH HHS [U01 AI069511, AI-25859,
AI-27665, AI-27761, AI-32782, AI-32783, AI-34853, AI-38855, AI-38858,
AI-46370, AI-68634, AI-68636, AI-69411, AI-69415, AI-69419, AI-69423,
AI-69424, AI-69428, AI-69432, AI-69434, AI-69439, AI-69450, AI-69452,
AI-69471, AI-69472, AI-69474, AI-69477, AI-69484, AI-69494, AI-69495,
AI-69501, AI-69511, AI-69513, AI-69532, AI-69556, P30 AI045008,
P30-AI-45008, U01 AI025859, U01 AI027659, U01 AI027659-18, U01 AI027665,
U01 AI032782, U01 AI032783, U01 AI034853, U01 AI038855, U01 AI038858,
U01 AI038858-09, U01 AI046370, U01 AI068634, U01 AI068636, U01
AI068636-04, U01 AI069411, U01 AI069415, U01 AI069419, U01 AI069423, U01
AI069424, U01 AI069428, U01 AI069432, U01 AI069434, U01 AI069439, U01
AI069450, U01 AI069452, U01 AI069471, U01 AI069472, U01 AI069474, U01
AI069477, U01 AI069484, U01 AI069494, U01 AI069495, U01 AI069501, U01
AI069511-03, U01 AI069513, U01 AI069532, U01 AI069556, UM1 AI068634, UM1
AI068636, UM1 AI069411, UM1 AI069415, UM1 AI069419, UM1 AI069423, UM1
AI069424, UM1 AI069428, UM1 AI069432, UM1 AI069434, UM1 AI069439, UM1
AI069450, UM1 AI069452, UM1 AI069471, UM1 AI069472, UM1 AI069474, UM1
AI069477, UM1 AI069484, UM1 AI069494, UM1 AI069495, UM1 AI069501, UM1
AI069511, UM1 AI069513, UM1 AI069532, UM1 AI069556]
NR 30
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 28
PY 2009
VL 23
IS 3
BP 357
EP 368
DI 10.1097/QAD.0b013e32831f9148
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 406WH
UT WOS:000263325100010
PM 19114860
ER
PT J
AU Lanoy, E
Dores, GM
Madeleine, MM
Toro, JR
Fraumeni, JF
Engels, EA
AF Lanoy, Emilie
Dores, Graca M.
Madeleine, Margaret M.
Toro, Jorge R.
Fraumeni, Joseph F., Jr.
Engels, Eric A.
TI Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in
the United States
SO AIDS
LA English
DT Article
DE AIDS; appendageal carcinoma; epidemiology; melanoma; Merkel cell
carcinoma; sebaceous carcinoma; skin cancer
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MUIR-TORRE-SYNDROME; SQUAMOUS-CELL
CARCINOMA; CUTANEOUS HUMAN PAPILLOMAVIRUSES; ORGAN TRANSPLANT
RECIPIENTS; SEBACEOUS GLAND CARCINOMA; SUN-EXPOSED SKIN; MICROSATELLITE
INSTABILITY; HIV-INFECTION; RISK-FACTORS
AB Objective: Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS.
Design: We linked data from population-based US AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS.
Methods: Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 cell count, and a geographic index of ultraviolet radiation exposure.
Results: From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR=1.3, 95% confidence interval 1.1-1.4, n=292 cases) and, more strongly, of Merkel cell carcinoma (SIR=11, 95% confidence interval 6.3-17, n=17) and sebaceous carcinoma (SIR=8.1, 95% confidence interval 3.2-17, n=7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (P trend 0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P=0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (P trend <10 (4) and P trend -10 (3), respectively).
Conclusion: Among persons with AIDS, there is a modest excess risk of melanoma, which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Lanoy, Emilie; Dores, Graca M.; Toro, Jorge R.; Fraumeni, Joseph F., Jr.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Lanoy, Emilie] Univ Paris 06, INSERM, U720, Paris, France.
[Lanoy, Emilie] Univ Paris 06, UPMC, UMR S720, Paris, France.
[Dores, Graca M.] US Dept Vet Affairs, Med Ctr, Med Serv, Oklahoma City, OK USA.
[Madeleine, Margaret M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7076, Rockville, MD 20892 USA.
EM engelse@exchange.nih.gov
RI Lanoy, Emilie/A-8541-2011
OI Lanoy, Emilie/0000-0002-4789-7770
FU Intramural Research Program of the National Cancer Institute
FX We are grateful for the contributions of many staff members at the
HIV/AIDS and cancer registries who collected the data, prepared data
files for the mathces, and facilitated the record linkages.; E.L. and
E.A.E. designed the study and conducted the statistical analyses.
G.M.D., J.R.T, and J.F.F contributed expertise regarding, skin cancer.
All authors contributed expertise regarding epidemiology methods and
participated in the interpretation of the data. M.M.M. and E.A.E.
provided data for the study. E.L. and E.A.E. drafted the article, and
all authors contributed to critical revision of the article.; The study
was supported by the Intramural Research Program of the National Cancer
Institute.
NR 42
TC 36
Z9 36
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JAN 28
PY 2009
VL 23
IS 3
BP 385
EP 393
DI 10.1097/QAD.0b013e3283213046
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 406WH
UT WOS:000263325100013
PM 19114864
ER
PT J
AU Trucksess, MW
Whitaker, TB
Weaver, CM
Slate, A
Giesbrecht, FG
Rader, JI
Betz, JM
AF Trucksess, Mary W.
Whitaker, Thomas B.
Weaver, Carol M.
Slate, Andrew
Giesbrecht, Francis G.
Rader, Jeanne I.
Betz, Joseph M.
TI Sampling and Analytical Variability Associated with the Determination of
Total Aflatoxins and Ochratoxin A in Powdered Ginger Sold As a Dietary
Supplement in Capsules
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE Sampling; analytical uncertainty; aflatoxins; ochratoxin A; ginger
capsules; dietary supplements
ID PART I; MYCOTOXINS; GINSENG; FOODS
AB The U.S. Food and Drug Administration is studying the need to monitor dietary supplements for mycotoxins such as total aflatoxins and ochratoxin A. An effective mycotoxin-monitoring program requires knowledge of the sampling and analytical variability associated with the determination of total aflatoxins (AF) and ochratoxin A (OTA) in dietary supplements. Three lots of ginger sold as a powder in capsule form and packaged in individual bottles were analyzed for both AF and OTA. The total variability associated with measuring AF and OTA in powdered ginger was partitioned into bottle-to-bottle, within bottle, and analytical variances. The variances were estimated using a nested design. For AF and OTA, the within-bottle variance associated with the 5 g laboratory sample size was the largest component of variability accounting for about 43% and 85% of the total variance, respectively; the analytical variance accounted for about 34% and 9% of the total variability, respectively; and the bottle-to-bottle variance accounted for about 23% and 7% of the total variance, respectively. When the total variance is converted into the coefficient of variation (CV or standard deviation relative to the mean concentration), the CV is lower for AF (16.9%) than OTA (24.7%).
C1 [Trucksess, Mary W.; Weaver, Carol M.; Rader, Jeanne I.] US FDA, College Pk, MD USA.
[Whitaker, Thomas B.] N Carolina State Univ, USDA, Raleigh, NC 27695 USA.
[Slate, Andrew] N Carolina State Univ, Dept Biol & Agr Engn, Raleigh, NC 27695 USA.
[Giesbrecht, Francis G.] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA.
[Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Trucksess, MW (reprint author), US FDA, College Pk, MD USA.
NR 12
TC 11
Z9 11
U1 1
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JAN 28
PY 2009
VL 57
IS 2
BP 321
EP 325
DI 10.1021/jf8017854
PG 5
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 397LU
UT WOS:000262665000001
PM 19105639
ER
PT J
AU Thomsen, M
Hall, FS
Uhl, GR
Caine, SB
AF Thomsen, Morgane
Hall, F. Scott
Uhl, George R.
Caine, S. Barak
TI Dramatically Decreased Cocaine Self-Administration in Dopamine But Not
Serotonin Transporter Knock-Out Mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cocaine; drug abuse; DAT; SERT; knock-out mouse; progressive ratio
ID PLACE PREFERENCE; DEFICIENT MICE; REWARD; AMPHETAMINE; MODULATION;
RECEPTORS; MONKEYS; LACKING; RAT
AB There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT(-/-)), the serotonin transporter (SERT(-/-)), or both (DAT(-/-) SERT(-/-)) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarly affected. We used a broad range of experimental conditions that included acquisition without previous training, behavior established with food training and subsequent testing with food, cocaine or a direct dopamine agonist as reinforcers, fixed ratio and progressive ratio schedules of reinforcement, and a reversal procedure. Wild-type mice readily acquired cocaine self-administration and showed dose-response curves characteristic of the schedule of reinforcement that was used. While some DAT(-/-) mice appeared to acquire cocaine self-administration transiently, almost all DAT(-/-) mice failed to self-administer cocaine reliably. Food-maintained behaviors were not decreased by the DAT mutation, and IV self-administration of a direct dopamine agonist was robust in the DAT(-/-) mice. In contrast to those mice, cocaine's reinforcing effects were not diminished in SERT(-/-) mice under any of the conditions tested, except for impaired initial acquisition of both food- and cocaine-maintained behavior. These findings support the notion that the DAT, but not the SERT, is critical in mediating the reinforcing effects of cocaine.
C1 [Thomsen, Morgane; Caine, S. Barak] Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA.
[Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Thomsen, M (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA.
EM mthomsen@mclean.harvard.edu
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU National Institute on Drug Abuse (NIDA)-National Institutes of Health
(NIH) [DA12142, DA14644, DA17323, DA14528, DA07252]; NIDA Intramural
Research-NIH-Department of Health and Human Services
FX This work was supported by grants from National Institute on Drug Abuse
(NIDA)-National Institutes of Health (NIH) (DA12142, DA14644, DA17323,
DA14528, DA07252) and in part from intramural funding from the NIDA
Intramural Research-NIH-Department of Health and Human Services (G. R.
U., F. S. H.). We thank Joon Y. Boon, Jennifer Dohrmann, Jill Berkowitz,
and Dana Angood for expert technical assistance.
NR 25
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U1 2
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 28
PY 2009
VL 29
IS 4
BP 1087
EP 1092
DI 10.1523/JNEUROSCI.4037-08.2009
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 400HQ
UT WOS:000262859000020
PM 19176817
ER
PT J
AU Weickert, TW
Goldberg, TE
Callicott, JH
Chen, Q
Apud, JA
Das, S
Zoltick, BJ
Egan, MF
Meeter, M
Myers, C
Gluck, MA
Weinberger, DR
Mattay, VS
AF Weickert, Thomas W.
Goldberg, Terry E.
Callicott, Joseph H.
Chen, Qiang
Apud, Jose A.
Das, Sumitra
Zoltick, Brad J.
Egan, Michael F.
Meeter, Martijn
Myers, Catherine
Gluck, Mark A.
Weinberger, Daniel R.
Mattay, Venkata S.
TI Neural Correlates of Probabilistic Category Learning in Patients with
Schizophrenia
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE schizophrenia; prefrontal cortex; caudate; parahippocampus; learning;
cognition
ID PARKINSONS-DISEASE; N-ACETYLASPARTATE; STRIATAL DOPAMINE; COGNITIVE
SKILL; BASAL GANGLIA; WHITE-MATTER; TASK; BRAIN; MEMORY; ACTIVATION
AB Functional neuroimaging studies of probabilistic category learning in healthy adults report activation of cortical-striatal circuitry. Based on previous findings of normal learning rate concurrent with an overall performance deficit in patients with schizophrenia, we hypothesized that relative to healthy adults, patients with schizophrenia would display preserved caudate nucleus and abnormal prefrontal cortex activation during probabilistic category learning. Forty patients with schizophrenia receiving antipsychotic medication and 25 healthy participants were assessed on interleaved blocks of probabilistic category learning and control tasks while undergoing blood oxygenation level-dependent functional magnetic resonance imaging. In addition to the whole sample of patients with schizophrenia and healthy adults, a subset of patients and healthy adults matched for good learning was also compared. In the whole sample analysis, patients with schizophrenia displayed impaired performance in conjunction with normal learning rate relative to healthy adults. The matched comparison of patients and healthy adults classified as good learners revealed greater caudate and dorsolateral prefrontal cortex activity in the healthy adults and greater activation in a more rostral region of the dorsolateral prefrontal, cingulate, parahippocampal and parietal cortex in patients. These results demonstrate that successful probabilistic category learning can occur in the absence of normal frontal-striatal function. Based on analyses of the patients and healthy adults matched on learning and performance, a minority of patients with schizophrenia achieve successful probabilistic category learning and performance levels through differential activation of a circumscribed neural network which suggests a compensatory mechanism in patients showing successful learning.
C1 [Weickert, Thomas W.] Univ New S Wales, Prince Wales Med Res Inst, Randwick, NSW 2031, Australia.
[Weickert, Thomas W.; Goldberg, Terry E.; Callicott, Joseph H.; Chen, Qiang; Apud, Jose A.; Das, Sumitra; Zoltick, Brad J.; Egan, Michael F.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Goldberg, Terry E.] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA.
[Meeter, Martijn] Vrije Univ Amsterdam, Dept Cognit Psychol, NL-1081 BT Amsterdam, Netherlands.
[Myers, Catherine] Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA.
[Gluck, Mark A.] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
RP Weickert, TW (reprint author), Univ New S Wales, Prince Wales Med Res Inst, Randwick, NSW 2031, Australia.
EM t.weickert@unsw.edu.au
RI Callicott, Joseph/C-9102-2009; Meeter, Martijn/A-2926-2009;
OI Callicott, Joseph/0000-0003-1298-3334; Meeter,
Martijn/0000-0002-5112-6717; Myers, Catherine/0000-0002-2776-4823
FU National Institutes of Health-National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health-National Institute of Mental Health.
NR 55
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U1 2
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 JAN 28
PY 2009
VL 29
IS 4
BP 1244
EP 1254
DI 10.1523/JNEUROSCI.4341-08.2009
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 400HQ
UT WOS:000262859000035
PM 19176832
ER
PT J
AU Wylie, BJ
Schwieters, CD
Oldfield, E
Rienstra, CM
AF Wylie, Benjamin J.
Schwieters, Charles D.
Oldfield, Eric
Rienstra, Chad M.
TI Protein Structure Refinement Using C-13 alpha Chemical Shift Tensors
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; INDIVIDUAL CARBON SITES;
MAGIC-ANGLE; C-13 NMR; AB-INITIO; MICROCRYSTALLINE PROTEIN;
ANTIMICROBIAL PEPTIDE; QUANTUM-CHEMISTRY; ANISOTROPY MEASUREMENTS
AB We have obtained the C-13 alpha chemical shift tensors for each amino acid in the protein GB1. We then developed a CST force field and incorporated this into the Xplor-NIH structure determination program. GB1 structures obtained by using CST restraints had improved precision over those obtained in the absence of CST restraints and were also more accurate. When combined with isotropic chemical shifts, distance, and vector angle restraints, the root-mean squared error with respect to existing X-ray structures was better than similar to 1.0 angstrom. These results are of broad general interest since they show that chemical shift tensors can be used in protein structure refinement, improving both structural accuracy and precision, opening up the way to accurate de novo structure determination.
C1 [Wylie, Benjamin J.; Oldfield, Eric; Rienstra, Chad M.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
[Schwieters, Charles D.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Rienstra, CM (reprint author), Univ Illinois, Dept Chem, 600 S Mathews Ave, Urbana, IL 61801 USA.
EM rienstra@scs.uiuc.edu
FU National Science Foundation [MCB 0347824]; National Institutes of Health
[GM73216, GM73770]; University of Illinois at Urbana-Champaign
FX This research was supported by the National Science Foundation (CAREER
Award, MCB 0347824 to C.M.R.), the CIT Intramural Research Program of
the NIH (C.D.S.), and in part by the National Institutes of Health
(GM73216 to E.O. and GM73770 to C.M.R.). We thank the NMR Facility at
the School of Chemical Sciences, University of Illinois at
Urbana-Champaign, for technical assistance.
NR 65
TC 36
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U1 1
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JAN 28
PY 2009
VL 131
IS 3
BP 985
EP 992
DI 10.1021/ja804041p
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 427PQ
UT WOS:000264791600038
PM 19123862
ER
PT J
AU Burkhart, BA
Ivey, ML
Archer, TK
AF Burkhart, Barbara A.
Ivey, Melissa L.
Archer, Trevor K.
TI Long-term low level glucocorticoid exposure induces persistent
repression in chromatin
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE Glucocorticoid resistance; Transcriptional repression; Chromatin; MMTV;
SGK
ID RECEPTOR-DEPENDENT TRANSCRIPTION; GENE-EXPRESSION; IN-VIVO; NUCLEAR
RECEPTORS; MMTV PROMOTER; HISTONE H1; KAPPA-B; RESISTANCE; STRESS; CELLS
AB Environmental exposure to low concentration hormones can have permanent epigenetic effects in animals and humans. The consequence of long-term low concentration glucocorticoid exposure was investigated in cell culture using glucocorticoid responsive genes organized in alternative chromatin structures. The MMTV promoter is induced by short-term glucocorticoid exposure on either an integrated (normal chromatin) or transient (unstructured chromatin) promoter. Longer hormone treatment causes a transient refractory repression of only the integrated promoter. Exposure to low concentrations of hormone for several passages persistently represses the integrated MMTV and endogenous glucocorticoid responsive promoters. The glucocorticoid receptor cannot bind to persistently repressed promoters. Induction by androgens is also inhibited on the repressed MMTV promoter. Similarly, osmotic stress induction of the endogenous Sgk gene is repressed. Persistent repression by glucocorticoids targets glucocorticoid responsive genes using a chromatin-dependent mechanism that disrupts binding of both GR-dependent and GR-indepenclent transcription complexes. Published by Elsevier Ireland Ltd.
C1 [Burkhart, Barbara A.; Ivey, Melissa L.; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, 111 Alexander Dr,POB 12233 MD C4-01, Res Triangle Pk, NC 27709 USA.
EM archer1@niehs.nih.gov
FU National Institute of Environmental Health Sciences; NIH: [Z01
ES071006-09]
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH: project number
Z01 ES071006-09.
NR 50
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Z9 5
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 27
PY 2009
VL 298
IS 1-2
BP 66
EP 75
DI 10.1016/j.mce.2008.10.011
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 398KX
UT WOS:000262732100009
PM 19007849
ER
PT J
AU Berezhkovskii, AM
Coppey, M
Shvartsman, SY
AF Berezhkovskii, Alexander M.
Coppey, Mathieu
Shvartsman, Stanislav Y.
TI Signaling gradients in cascades of two-state reaction-diffusion systems
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; TERMINAL BODY PATTERN; DROSOPHILA-EMBRYO;
POSITIONAL INFORMATION; MORPHOGEN GRADIENTS; GENE-EXPRESSION;
MITOTIC-CYCLES; NUCLEAR; TORSO; DYNAMICS
AB Biological networks frequently use cascades, generally defined as chain-like arrangements of similar modules. Spatially lumped cascades can serve as noise filters, time-delay, or thresholding elements. The operation and functional capabilities of spatially distributed cascades are much less understood. Motivated by studies of pattern formation in the early Drosophila embryo, we analyze cascades of 2-state reaction-diffusion systems. At each stage within such as a cascade, a diffusible particle is reversibly bound by immobile traps and can be annihilated in both mobile and immobile states. When trapped, these particles drive the next stage by converting mobile particles of a different type from a passive to active form. The cascade initiated by injection of mobile particles into the first stage. We derive analytical expressions for the steady-state concentration profiles of mobile and immobile particles and analyze how the output of a cascade is controlled by properties of the constituent stages.
C1 [Coppey, Mathieu; Shvartsman, Stanislav Y.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
[Coppey, Mathieu; Shvartsman, Stanislav Y.] Princeton Univ, Dept Chem Engn, Princeton, NJ 08540 USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Shvartsman, SY (reprint author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
EM stas@princeton.edu
FU National Institutes of Health, [HHSN266200500021C, N01-AI-50021]; Center
for Information Technology [P50 GM071508, R01 RM078079]
FX We thank Alistair Boettiger for numerous helpful discussions. This work
was supported by the Intramural Research Program of the National
Institutes of Health, Center for Information Technology ( A. M. B.), by
Grants P50 GM071508 and R01 RM078079 from the National Institutes of
Health ( to S. Y. S.), and by National Institutes of Health contract no.
HHSN266200500021C, ADB no. N01-AI-50021 ( S. Y. S. and M. C.).
NR 38
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U1 1
U2 9
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 JAN 27
PY 2009
VL 106
IS 4
BP 1087
EP 1092
DI 10.1073/pnas.0811807106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600025
PM 19147842
ER
PT J
AU Calado, RT
Regal, JA
Hills, M
Yewdell, WT
Dalmazzo, LF
Zago, MA
Lansdorp, PM
Hogge, D
Chanock, SJ
Estey, EH
Falcao, RP
Young, NS
AF Calado, Rodrigo T.
Regal, Joshua A.
Hills, Mark
Yewdell, William T.
Dalmazzo, Leandro F.
Zago, Marco A.
Lansdorp, Peter M.
Hogge, Donna
Chanock, Stephen J.
Estey, Elihu H.
Falcao, Roberto P.
Young, Neal S.
TI Constitutional hypomorphic telomerase mutations in patients with acute
myeloid leukemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE risk factor; telomere; dyskeratosis congenita; cancer
ID BRITISH COOPERATIVE GROUP; BONE-MARROW FAILURE; DYSKERATOSIS-CONGENITA;
REVERSE-TRANSCRIPTASE; FUNCTIONAL-CHARACTERIZATION; HEMATOLOGIC
DISORDERS; GENOME INSTABILITY; PULMONARY-FIBROSIS; APLASTIC-ANEMIA;
CANCER
AB Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P<0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability.
C1 [Calado, Rodrigo T.; Regal, Joshua A.; Yewdell, William T.; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Chanock, Stephen J.] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Dalmazzo, Leandro F.; Zago, Marco A.; Falcao, Roberto P.] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Cell Based Therapy, Dept Internal Med, BR-14048900 Ribeirao Preto, Brazil.
[Estey, Elihu H.] Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA.
[Hills, Mark; Lansdorp, Peter M.; Hogge, Donna] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 4E6, Canada.
[Lansdorp, Peter M.; Hogge, Donna] Univ British Columbia, Ctr Canc, Dept Med, Vancouver, BC V6T 1ZA, Canada.
RP Calado, RT (reprint author), 10 Ctr Dr,Bldg 10-CRC,Room 3E-5140, Bethesda, MD 20892 USA.
EM calador@nhlbi.nih.gov
RI Calado, Rodrigo/G-2619-2011; Celulas tronco, Inct/I-1921-2013
FU National Institutes of Health Intramural Research Program; Fundacao de
Amparo a Pesquisa do Estado de Sao Paulo; Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico; Canadian Institutes of Health
Research [MOP38075, GMH79042]
FX This work was supported by the National Institutes of Health Intramural
Research Program (R. T. C., S. J. C., and N. S. Y.), Fundacao de Amparo
a Pesquisa do Estado de Sao Paulo and Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (L. F. D., M. A. Z., and R. P.
F.), and Canadian Institutes of Health Research Grants MOP38075 and
GMH79042 (to P. M. L.).
NR 36
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U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 27
PY 2009
VL 106
IS 4
BP 1187
EP 1192
DI 10.1073/pnas.0807057106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600042
PM 19147845
ER
PT J
AU Chien, AJ
Moore, EC
Lonsdorf, AS
Kulikauskas, RM
Rothberg, BG
Berger, AJ
Major, MB
Hwang, ST
Rimm, DL
Moon, RT
AF Chien, Andy J.
Moore, Erin C.
Lonsdorf, Anke S.
Kulikauskas, Rima M.
Rothberg, Bonnie Gould
Berger, Aaron J.
Major, Michael B.
Hwang, Sam T.
Rimm, David L.
Moon, Randall T.
TI Activated Wnt/beta-catenin signaling in melanoma is associated with
decreased proliferation in patient tumors and a murine melanoma model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE differentiation; prognosis; metastasis; WNT5A; B16 model; microarray
ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN-JOINT-COMMITTEE; BETA-CATENIN;
PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; COLORECTAL-CANCER;
WILMS-TUMOR; CELL-LINES; STEM-CELLS; EXON 3
AB This study demonstrates that in malignant melanoma, elevated levels of nuclear beta-catenin in both primary tumors and metastases correlate with reduced expression of a marker of proliferation and with improved survival, in contrast to colorectal cancer. The reduction in proliferation observed in vivo is recapitulated in B16 murine melanoma cells and in human melanoma cell lines cultured in vitro with either WNT3A or small-molecule activators of beta-catenin signaling. Consistent with these results, B16 melanoma cells expressing WNT3A also exhibit decreased tumor size and decreased metastasis when implanted into mice. Genome-wide transcriptional profiling reveals that WNT3A up-regulates genes implicated in melanocyte differentiation, several of which are down-regulated with melanoma progression. These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/beta-catenin signaling in normal melanocyte development, thereby altering melanoma cell fate to one that may be less proliferative and potentially less aggressive. Our results may explain the observed loss of nuclear beta-catenin with melanoma progression in human tumors, which could reflect a dysregulation of cellular differentiation through a loss of homeostatic Wnt/beta-catenin signaling.
C1 [Chien, Andy J.; Kulikauskas, Rima M.; Major, Michael B.; Moon, Randall T.] Univ Washington, Sch Med, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA.
[Chien, Andy J.; Moore, Erin C.; Kulikauskas, Rima M.] Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA.
[Moon, Randall T.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA.
[Moore, Erin C.; Major, Michael B.; Moon, Randall T.] Natl Canc Ctr, Howard Hughes Med Inst, Bethesda, MD 20815 USA.
[Moore, Erin C.; Major, Michael B.; Moon, Randall T.] Natl Canc Ctr, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20815 USA.
[Rothberg, Bonnie Gould; Berger, Aaron J.; Rimm, David L.] Yale Univ, Dept Pathol, New Haven, CT 06520 USA.
RP Moon, RT (reprint author), Univ Washington, Sch Med, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA.
EM rtmoon@u.washington.edu
RI Moon, Randall/B-1743-2014;
OI Moon, Randall/0000-0002-9352-1408; Major, Michael/0000-0002-6753-8513
FU National Institutes of Health-German Research Foundation; Center for
Cancer Research; American Skin Association; Dermatology Foundation;
National Cancer Institute
FX E. M. was supported as a Medical Fellow, M. M. as an Associate, and R.
M. as an Investigator by the Howard Hughes Medical Institute. A. L. is
funded by a National Institutes of Health-German Research Foundation
Research Career Transition Award. Research support was provided in part
by intramural research funds from the Center for Cancer Research ( to S.
H. and A. L.). A. C. received funding support through a Research Scholar
Award from the American Skin Association, a Career Award from the
Dermatology Foundation, and a K08 Career Development Award from the
National Cancer Institute. We thank Sancy Leachman, Pamela Cassidy, and
Brett Milash at the University of Utah for their assistance in
facilitating our microarray studies. We also thank the staff of the
University of Washington Department of Biostatistics for their
consultative guidance in our statistical analysis.
NR 53
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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 JAN 27
PY 2009
VL 106
IS 4
BP 1193
EP 1198
DI 10.1073/pnas.0811902106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600043
PM 19144919
ER
PT J
AU Wang, GJ
Volkow, ND
Telang, F
Jayne, M
Ma, YM
Pradhan, K
Zhu, W
Wong, CT
Thanos, PK
Geliebter, A
Biegon, A
Fowler, JS
AF Wang, Gene-Jack
Volkow, Nora D.
Telang, Frank
Jayne, Millard
Ma, Yeming
Pradhan, Kith
Zhu, Wei
Wong, Christopher T.
Thanos, Panayotis K.
Geliebter, Allan
Biegon, Anat
Fowler, Joanna S.
TI Evidence of gender differences in the ability to inhibit brain
activation elicited by food stimulation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE amygdala; cognitive inhibition; food stimuli; Orbitofrontal cortex
ID MEDIAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS;
MENSTRUAL-CYCLE; BASOLATERAL AMYGDALA; NEURAL RESPONSES; DORSAL
STRIATUM; EATING BEHAVIOR; REWARD; DOPAMINE
AB Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[ (18)F] fluoro-D-glucose ((18)FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are regions involved in emotional regulation, conditioning, and motivation. The suppressed activation of the orbitofrontal cortex with inhibition in men was associated with decreases in self-reports of hunger, which corroborates the involvement of this region in processing the conscious awareness of the drive to eat. This finding suggests a mechanism by which cognitive inhibition decreases the desire for food and implicates lower ability to suppress hunger in women as a contributing factor to gender differences in obesity.
C1 [Wang, Gene-Jack; Wong, Christopher T.; Biegon, Anat; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Volkow, Nora D.; Telang, Frank; Jayne, Millard; Ma, Yeming; Thanos, Panayotis K.] NIAAA NIDA, Rockville, MD 20857 USA.
[Pradhan, Kith; Zhu, Wei] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[Geliebter, Allan] St Lukes Roosevelt Hosp, New York, NY 10025 USA.
RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM gjwang@bnl.gov
FU Department of Energy OBER [DE-ACO2 -98CH10886]; National Institute on
Drug Abuse [DA6891, DA6278]; National Institute on Alcohol Abuse and
Alcoholism [AA9481, Y1AA3009]; General Clinical Research Center at Stony
Brook University Hospital [NIH MO1RR 10710]
FX We thank all of the subjects who participated in this study. We also
thank K. Torres for Institutional Review Board correspondence and study
compliance; D. Schlyer and M. Schueller for Cyclotron operations; D.
Alexoff, P. Vaska, and D. Warner for PET operations; C. Shea, Y. Xu, L.
Muench, and P. King for radiotracer preparation and analysis; P. Carter
and B. Hubbard for patient care and A. Ruggiero for manuscript
submission. This work was supported by the Department of Energy OBER
(DE-ACO2 -98CH10886), National Institute on Drug Abuse (DA6891 &
DA6278), National Institute on Alcohol Abuse and Alcoholism (AA9481 &
Y1AA3009), and the General Clinical Research Center at Stony Brook
University Hospital (NIH MO1RR 10710).
NR 64
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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 JAN 27
PY 2009
VL 106
IS 4
BP 1249
EP 1254
DI 10.1073/pnas.0807423106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600053
PM 19164587
ER
PT J
AU Nagappan, G
Zaitsev, E
Senatorov, VV
Yang, JM
Hempstead, BL
Lu, B
AF Nagappan, Guhan
Zaitsev, Eugene
Senatorov, Vladimir V., Jr.
Yang, Jianmin
Hempstead, Barbara L.
Lu, Bai
TI Control of extracellular cleavage of ProBDNF by high frequency neuronal
activity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE BDNF; hippocampus; LTP; proteases; tPA
ID ACTIVITY-DEPENDENT RELEASE; TISSUE-PLASMINOGEN ACTIVATOR;
LONG-TERM-POTENTIATION; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR;
HIPPOCAMPAL-NEURONS; BDNF; PLASTICITY; SECRETION; LTP
AB Pro-and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect proBDNF or mBDNF, we show that low-frequency stimulation induced predominant proBDNF secretion in cultured hippocampal neurons. In contrast, high-frequency stimulation preferentially increased extracellular mBDNF. Inhibition of extracellular, but not intracellular cleavage of proBDNF greatly reduced high-frequency stimulation-induced extracellular mBDNF. Moreover, high-frequency, but not low-frequency stimulation selectively induced the secretion of tissue plasminogen activator, a key protease involved in extracellular proBDNF to mBDNF conversion. Thus, high-frequency neuronal activity controls the ratio of extracellular proBDNF/mBDNF by regulating the secretion of extracellular proteases. Our study demonstrates activity-dependent control of extracellular proteolytic cleavage of a secretory protein, and reveals an important mechanism that controls diametrically opposed functions of BDNF isoforms.
C1 [Nagappan, Guhan; Zaitsev, Eugene; Senatorov, Vladimir V., Jr.; Lu, Bai] NICHHD, Sect Neural Dev & Plast, Gene Cognit & Psychosis Program, NIMH,NIH, Bethesda, MD 20892 USA.
[Yang, Jianmin; Hempstead, Barbara L.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plast, Gene Cognit & Psychosis Program, NIMH,NIH, 35 Lincoln Dr, Bethesda, MD 20892 USA.
EM bailu@mail.nih.gov
RI Lu, Bai/A-4018-2012
FU Intramural Research Programs of National Institute of Child Health;
National Institue of Mental Health
FX We thank Drs. Newton Woo and Keri Martinowich for their thoughtful
comments and suggestions. The rat tPA-Venus in the pEGFP-N1 vector was
kindly provided by Dr. Wolfhard Almers. Microscopy imaging was performed
at the Microscopy & Imaging Core (National Institute of Child Health and
Development, National Institutes of Health) with the assistance of Dr.
Vincent Schram. This work is supported by the Intramural Research
Programs of National Institute of Child Health and National Institue of
Mental Health.
NR 34
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U2 7
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 JAN 27
PY 2009
VL 106
IS 4
BP 1267
EP 1272
DI 10.1073/pnas.0807322106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600056
PM 19147841
ER
PT J
AU Li, YZ
Perry, T
Kindy, MS
Harvey, BK
Tweedie, D
Holloway, HW
Powers, K
Shen, H
Egan, JM
Sambamurti, K
Brossi, A
Lahiri, DK
Mattson, MP
Hoffer, BJ
Wang, Y
Greig, NH
AF Li, Yazhou
Perry, TracyAnn
Kindy, Mark S.
Harvey, Brandon K.
Tweedie, David
Holloway, Harold W.
Powers, Kathleen
Shen, Hui
Egan, Josephine M.
Sambamurti, Kumar
Brossi, Arnold
Lahiri, Debomoy K.
Mattson, Mark P.
Hoffer, Barry J.
Wang, Yun
Greig, Nigel H.
TI GLP-1 receptor stimulation preserves primary cortical and dopaminergic
neurons in cellular and rodent models of stroke and Parkinsonism
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diabetes; exendin-4; neurodegeneration; neuroprotection; stroke
ID GLUCAGON-LIKE PEPTIDE-1; NERVE GROWTH-FACTOR; CEREBELLAR GRANULE
NEURONS; DIABETES-MELLITUS; CYCLIC-AMP; CEREBRAL-ISCHEMIA; ANIMAL-MODEL;
IN-VITRO; APOPTOSIS; DISEASE
AB Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), is the first of this new class of antihyperglycemia drugs approved to treat T2DM. GLP-1Rs are coupled to the cAMP second messenger pathway and, along with pancreatic cells, are expressed within the nervous system of rodents and humans, where receptor activation elicits neurotrophic actions. We detected GLP-1R mRNA expression in both cultured embryonic primary cerebral cortical and ventral mesencephalic (dopaminergic) neurons. These cells are vulnerable to hypoxia-and 6-hydroxydopamine-induced cell death, respectively. We found that GLP-1 and Ex-4 conferred protection in these cells, but not in cells from Glp1r knockout (-/-) mice. Administration of Ex-4 reduced brain damage and improved functional outcome in a transient middle cerebral artery occlusion stroke model. Ex-4 treatment also protected dopaminergic neurons against degeneration, preserved dopamine levels, and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our findings demonstrate that Ex-4 can protect neurons against metabolic and oxidative insults, and they provide preclinical support for the therapeutic potential for Ex-4 in the treatment of stroke and PD.
C1 [Li, Yazhou; Perry, TracyAnn; Tweedie, David; Holloway, Harold W.; Mattson, Mark P.; Greig, Nigel H.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Kindy, Mark S.; Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Kindy, Mark S.] Neurol Testing Serv, Mt Pleasant, SC 29466 USA.
[Harvey, Brandon K.; Powers, Kathleen; Shen, Hui; Wang, Yun] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Egan, Josephine M.] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
[Lahiri, Debomoy K.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Hoffer, Barry J.] Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Greig, NH (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM greign@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU Intramural Research Programs of the National Institute on Aging and the
National Institute on Drug Abuse
FX This work was supported in part by the Intramural Research Programs of
the National Institute on Aging and the National Institute on Drug
Abuse. Animal studies were performed in accordance with approved
protocols, in compliance with the National Institutes of Health's
Guidelines for Animal Experimentation. Daniel J. Drucker, MD, University
of Toronto, kindly provided the Glp1r-/- mice.
NR 44
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U2 21
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 JAN 27
PY 2009
VL 106
IS 4
BP 1285
EP 1290
DI 10.1073/pnas.0806720106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399XC
UT WOS:000262831600059
PM 19164583
ER
PT J
AU Volfovsky, N
Oleksyk, TK
Cruz, KC
Truelove, AL
Stephens, RM
Smith, MW
AF Volfovsky, Natalia
Oleksyk, Taras K.
Cruz, Kristine C.
Truelove, Ann L.
Stephens, Robert M.
Smith, Michael W.
TI Genome and gene alterations by insertions and deletions in the evolution
of human and chimpanzee chromosome 22
SO BMC GENOMICS
LA English
DT Article
ID DNA-SEQUENCES; HAPLOTYPE MAP; DISEASE; POLYMORPHISM; DIVERGENCE; INDELS;
DUPLICATIONS; ALIGNMENT; MAJORITY; ELEMENTS
AB Background: Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels) play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes.
Results: Specifically, we identified 6,279 indels of 10 bp or greater in a similar to 33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i) those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb) region, (ii) those with at least one exact copy found nearby, and (iii) those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429) were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans.
Conclusion: Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are substantial differences in representation of indel classes among genomic elements, most likely caused by differences in their evolutionary histories. Using local sequence context, we predicted origins and phylogenetic relationships of gene-impacting indels in primate species. These results suggest that genome plasticity is a major force behind speciation events separating the great ape lineages.
C1 [Oleksyk, Taras K.; Cruz, Kristine C.; Truelove, Ann L.; Smith, Michael W.] NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA.
[Volfovsky, Natalia; Stephens, Robert M.] NCI, Adv Biochem Comp Ctr, Adv Technol Program, SAIC Frederick, Ft Detrick, MD 21702 USA.
[Oleksyk, Taras K.; Truelove, Ann L.; Smith, Michael W.] NCI, Basic Res Program, SAIC Frederick, Ft Detrick, MD 21702 USA.
[Oleksyk, Taras K.; Truelove, Ann L.; Smith, Michael W.] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00681 USA.
RP Smith, MW (reprint author), NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA.
EM natalia@ncifcrf.gov; dna@uprm.edu; cruzkc@gmail.com;
anntruelove@gmail.com; bobs@ncifcrf.gov; smithm@ncifcrf.gov
RI Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013
OI Taras, Oleksyk/0000-0002-8148-3918
FU National Cancer Institute; National Institutes of Health [N01-CO-12400]
FX We thank the patients and staff of all the participating cohorts in the
study. We thank Drs. Cheryl Winkler, Michael Dean, and Mary Carrington
for helpful insights in developing the ideas for this manuscript. We are
also grateful to Randy Johnson, Kai Zhao, Bailey Kessing, and Michael
Malasky for their assistance. We would like to thank Maritta Grau and
Allen Kane from SAIC- Frederick Scientific Publications, Graphics and
Media for their help with writing and the display items. 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. The project included in this manuscript has been funded
in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract N01-CO-12400.
NR 48
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U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JAN 26
PY 2009
VL 10
AR 51
DI 10.1186/1471-2164-10-51
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 430EE
UT WOS:000264970800001
PM 19171065
ER
PT J
AU Taylor-Cousar, JL
Zariwala, MA
Burch, LH
Pace, RG
Drumm, ML
Calloway, H
Fan, HY
Weston, BW
Wright, FA
Knowles, MR
AF Taylor-Cousar, Jennifer L.
Zariwala, Maimoona A.
Burch, Lauranell H.
Pace, Rhonda G.
Drumm, Mitchell L.
Calloway, Hollin
Fan, Haiying
Weston, Brent W.
Wright, Fred A.
Knowles, Michael R.
CA Gene Modifier Study Grp
TI Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of
Infection and Cystic Fibrosis Lung Disease Severity
SO PLOS ONE
LA English
DT Article
AB Background: The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF.
Methods and Principal Findings: Clinical information and DNA was collected on > 800 patients with the Delta F508/Delta F508 genotype. Patients in the most severe and mildest quartiles for lung phenotype were enrolled. Blood samples underwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90-95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that accounts for > 95% of the incidence of nonsecretor phenotype in Caucasians was completed using an ABI Taqman assay. The overall prevalence of ABO types, and of FUT2 (secretor) and FUT 3 (Lewis) alleles was consistent with that found in the Caucasian population. There was no difference in distribution of ABH type in the severe versus mild patients, or the age of onset of Pseudomonas aeruginosa infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type.
Conclusions and Significance: Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes were not shown to associate with severity of CF lung disease, or age of onset of P. aeruginosa infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the Delta F508 mutation.
C1 Univ New Mexico, Hlth Sci Ctr, Div Pulm, Albuquerque, NM 87131 USA.
[Zariwala, Maimoona A.; Pace, Rhonda G.; Calloway, Hollin; Knowles, Michael R.] Univ N Carolina, Cystic Fibrosis Pulmonary Res & Treatment Ctr, Chapel Hill, NC USA.
[Burch, Lauranell H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Wright, Fred A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Fan, Haiying; Weston, Brent W.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Drumm, Mitchell L.] Case Western Reserve Univ, Dept Pediat, Div Pediat Pulmonary, Cleveland, OH 44106 USA.
RP Taylor-Cousar, JL (reprint author), Univ New Mexico, Hlth Sci Ctr, Div Pulm, Albuquerque, NM 87131 USA.
EM JTCousar@salud.unm.edu
FU NIH [HL068890, 1F32HL082207-01]; GlaxoSmithKline Pulmonary Fellowship
Award
FX This work was supported by NIH HL068890, NIH 1F32HL082207-01, and the
GlaxoSmithKline Pulmonary Fellowship Award. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
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U1 2
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 JAN 26
PY 2009
VL 4
IS 1
BP CP5
EP U11
AR e4270
DI 10.1371/journal.pone.0004270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437JE
UT WOS:000265482800001
PM 19169360
ER
PT J
AU Loucks, FA
Schroeder, EK
Zommer, AE
Hilger, S
Kelsey, NA
Bouchard, RJ
Blackstone, C
Brewster, JL
Linseman, DA
AF Loucks, F. Alexandra
Schroeder, Emily K.
Zommer, Amelia E.
Hilger, Shea
Kelsey, Natalie A.
Bouchard, Ron J.
Blackstone, Craig
Brewster, Jay L.
Linseman, Daniel A.
TI Caspases indirectly regulate cleavage of the mitochondrial fusion GTPase
OPA1 in neurons undergoing apoptosis
SO BRAIN RESEARCH
LA English
DT Article
DE Optic atrophy type 1 (OPA1); Dynamin GTPase; Mitochondrial fusion;
Apoptosis; Caspase; Cerebellar granule neuron
ID CEREBELLAR GRANULE NEURONS; DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC
ATROPHY; CYTOCHROME-C RELEASE; INDUCED CELL-DEATH; PROTEOLYTIC CLEAVAGE;
OXIDATIVE STRESS; MAMMALIAN-CELLS; MESSENGER-RNA; NITRIC-OXIDE
AB The critical processes of mitochondrial fission and fusion are regulated by members of the dynamin family of GTPases. Imbalances in mitochondrial fission and fusion contribute to neuronal cell death. For example, increased fission mediated by the dynamin-related GTPase, Drp1, or decreased fusion resulting from inactivating mutations in the OPA1 GTPase, causes neuronal apoptosis and/or neurodegeneration. Recent studies indicate that post-translational processing regulates OPA1 function in non-neuronal cells and moreover, aberrant processing of OPA1 is induced during apoptosis. To date, the post-translational processing of OPA1 during neuronal apoptosis has not been examined. Here, we show that cerebellar granule neurons (CGNs) or neuroblastoma cells exposed to pro-apoptotic stressors display a novel N-terminal cleavage of OPA1 which is blocked by either pan-caspase or caspase-8 selective inhibitors. OPA1 cleavage occurs concurrently with mitochondrial fragmentation and cytochrome c release in CGNs deprived of depolarizing potassium (5K condition). Although a caspase-8 selective inhibitor prevents both 5K-induced OPA1 cleavage and mitochondrial fragmentation, recombinant caspase-8 fails to cleave OPA1 in vitro. In marked contrast, either caspase-8 or caspase-3 stimulates OPA1 cleavage in digitonin-permeabilized rat brain mitochondria, suggesting that OPA1 is cleaved by an intermembrane space protease which is regulated by active caspases. Finally, the N-terminal truncation of OPA1 induced during neuronal apoptosis removes an essential residue (K301) within the GTPase domain. These data are the first to demonstrate OPA1 cleavage during neuronal apoptosis and they implicate caspases as indirect regulators of OPA1 processing in degenerating neurons. Published by Elsevier B.V.
C1 [Zommer, Amelia E.; Kelsey, Natalie A.; Linseman, Daniel A.] Univ Denver, Dept Biol Sci, Denver, CO 80208 USA.
[Zommer, Amelia E.; Kelsey, Natalie A.; Linseman, Daniel A.] Univ Denver, Eleanor Roosevelt Inst, Denver, CO 80208 USA.
[Loucks, F. Alexandra; Schroeder, Emily K.; Bouchard, Ron J.; Linseman, Daniel A.] Vet Affairs Med Ctr, Res Serv, Denver, CO USA.
[Hilger, Shea; Brewster, Jay L.] Pepperdine Univ, Div Nat Sci, Malibu, CA 90265 USA.
[Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, NIH, Bethesda, MD USA.
[Linseman, Daniel A.] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Clin Pharmacol & Toxicol, Denver, CO 80262 USA.
RP Linseman, DA (reprint author), Univ Denver, Dept Biol Sci, FW Olin Hall,Rm 102,2190 E Iliff Ave, Denver, CO 80208 USA.
EM daniel.linseman@du.edu
FU Department of Veterans Affairs; National Institutes of Health
FX This study was supported by a Merit Review grant from the Department of
Veterans Affairs (to D.A.L.) and an AREA grant from the National
Institutes of Health (to J.L.B.). We thank Dr. Klaus Aktories and Dr.
Torsten Giesemann for C. difficile toxin B and Dr. Stephen Fisher for
SH-SY5Y cells. We acknowledge Shoshona Le, Angela Zimmermann, and Ingrid
Anderson for technical assistance.
NR 41
TC 11
Z9 12
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JAN 23
PY 2009
VL 1250
BP 63
EP 74
DI 10.1016/j.brainres.2008.10.081
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 407WI
UT WOS:000263394600007
PM 19046944
ER
PT J
AU Macova, M
Pavel, J
Saavedra, JM
AF Macova, Miroslava
Pavel, Jaroslav
Saavedra, Juan M.
TI A peripherally administered, centrally acting angiotensin II AT(2)
antagonist selectively increases brain AT(1) receptors and decreases
brain tyrosine hydroxylase transcription, pituitary vasopressin and ACTH
SO BRAIN RESEARCH
LA English
DT Article
DE Brain Angiotensin II receptor; Central sympathetic system; Pituitary
hormone; Locus coeruleus; Paraventricular nucleus; Inferior olive
ID SPONTANEOUSLY HYPERTENSIVE-RATS; GENE-DISRUPTED MICE; MESSENGER-RNA
EXPRESSION; TYPE-2 RECEPTOR; BLOOD-PRESSURE; NORMOTENSIVE RATS;
ISOLATION STRESS; PASTE STANDARDS; AT1; SUBTYPES
AB The physiological actions of brain Angiotensin II AT(2) receptors and their relationship to Angiotensin II AT(1) receptors remain controversial. To further clarify their role, we determined to what extent systemic administration of an AT(2) receptor antagonist affected AT(2) receptor binding within the brain and the expression of AT(1) receptors. For this purpose, we subcutaneously administered the AT(2) receptor antagonist PD123319 (1 mg/kg/day) to adult male rats for two weeks via osmotic minipumps. We also studied the content of pituitary adrenocorticotropic hormone and vasopressin, representative of hypothalamic-pituitary-adrenal axis activation, and the tyrosine hydroxylase gene expression in the locus coeruleus as a measure of central norepinephrine function. We found significant decreases in AT(2) receptor binding in brain areas inside the blood brain barrier, the inferior olive and the locus coeruleus. AT(2) receptor blockade increased AT(1) receptor binding and mRNA expression not only in the subfornical organ and the median eminence, situated outside the blood brain barrier, but also in the hypothalamic paraventricular nucleus, located inside the blood brain barrier. These changes paralleled decreased expression of tyrosine hydroxylase mRNA in the locus coeruleus and decreased pituitary adrenocorticotropic and vasopressin content. Our results demonstrate that sustained peripheral administration of an AT(2) antagonist decreases binding to brain AT(2) receptors, indicating that this drug is a useful tool for the study of their central role. AT(2) receptor activity inhibition up-regulates AT(1) receptor expression in specific brain areas. Blockade of brain AT(2) receptors is compatible with enhanced hypothalamic-pituitary-adrenal axis and decreased central sympathetic system activity. Published by Elsevier B.V.
C1 [Macova, Miroslava; Pavel, Jaroslav; Saavedra, Juan M.] NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
FU Division of intramural Research Programs, National institute of Mental
Health, Department of Health and Human Services, USA
FX This study was supported by the Division of intramural Research
Programs, National institute of Mental Health, Department of Health and
Human Services, USA.
NR 56
TC 20
Z9 22
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JAN 23
PY 2009
VL 1250
BP 130
EP 140
DI 10.1016/j.brainres.2008.11.006
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 407WI
UT WOS:000263394600014
PM 19038235
ER
PT J
AU Forgacs, E
Sakamoto, T
Cartwright, S
Belknap, B
Kovacs, M
Toth, J
Webb, MR
Sellers, JR
White, HD
AF Forgacs, Eva
Sakamoto, Takeshi
Cartwright, Suzanne
Belknap, Betty
Kovacs, Mihaly
Toth, Judit
Webb, Martin R.
Sellers, James R.
White, Howard D.
TI Switch 1 Mutation S217A Converts Myosin V into a Low Duty Ratio Motor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID KINETIC MECHANISM; NECK LENGTH; ACTOMYOSIN; PROCESSIVITY; PHOSPHATE;
DOMAIN; ACTIN; ADP; NUCLEOTIDE; RESOLUTION
AB We have determined the kinetic mechanism and motile properties of the switch 1 mutant S217A of myosin Va. Phosphate dissociation from myosin V-ADP-P(i) (inorganic phosphate) and actomyosin V-ADP-P(i) and the rate of the hydrolysis step ( myosin V-ATP -> myosin V-ADP-P(i)) were all similar to 10-fold slower in the S217A mutant than in wild type (WT) myosin V, resulting in a slower steady-state rate of basal and filamentous actin (actin)-activated ATP hydrolysis. Substrate binding and ADP dissociation kinetics were all similar to or slightly faster in S217A than in WT myosin V and mechanochemical gating of the rates of dissociation of ADP between trail and lead heads is maintained. The reduction in the rate constants of the hydrolysis and phosphate dissociation steps reduces the duty ratio from similar to 0.85 in WT myosin V to similar to 0.25 in S217A and produces a motor in which the average run length on actin at physiological concentrations of ATP is reduced 10-fold. Thus we demonstrate that, by mutational perturbation of the switch 1 structure, myosin V can be converted into a low duty ratio motor that is processive only at low substrate concentrations.
C1 [Forgacs, Eva; Cartwright, Suzanne; Belknap, Betty; White, Howard D.] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA.
[Webb, Martin R.] Natl Inst Med Res, Div Phys Biochem, London NW7 1AA, England.
[Sakamoto, Takeshi; Kovacs, Mihaly; Toth, Judit; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Kovacs, Mihaly] Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary.
[Toth, Judit] Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1113 Budapest, Hungary.
RP White, HD (reprint author), Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA.
EM whitehd@evms.edu
RI Kovacs, Mihaly/A-6841-2011
FU National Institutes of Health [EB00209]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant EB00209 ( to H. D. W.).
NR 37
TC 19
Z9 19
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 23
PY 2009
VL 284
IS 4
BP 2138
EP 2149
DI 10.1074/jbc.M805530200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 395TE
UT WOS:000262545600023
PM 19008235
ER
PT J
AU Utreras, E
Futatsugi, A
Rudrabhatla, P
Keller, J
Iadarola, MJ
Pant, HC
Kulkarni, AB
AF Utreras, Elias
Futatsugi, Akira
Rudrabhatla, Parvathi
Keller, Jason
Iadarola, Michael J.
Pant, Harish C.
Kulkarni, Ashok B.
TI Tumor Necrosis Factor-alpha Regulates Cyclin-dependent Kinase 5 Activity
during Pain Signaling through Transcriptional Activation of p35
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NERVE GROWTH-FACTOR; TNF-ALPHA; PC12 CELLS; INFLAMMATORY HYPERALGESIA;
NEUROPATHIC PAIN; MESSENGER-RNA; UP-REGULATION; SPINAL-CORD; CDK5;
PHOSPHORYLATION
AB Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/ threonine kinase. We have previously reported that Cdk5 participates in the regulation of nociceptive signaling, and the expression of Cdk5 and its activator, p35, are up-regulated in nociceptive neurons during peripheral inflammation. The aim of our current study was to identify the proinflammatory molecules that regulate Cdk5/p35 activity in response to inflammation. We constructed a vector that contains the mouse p35 promoter driving luciferase expression. We transiently transfected this vector in PC12 cells to test the effect of several cytokines on p35 transcriptional activity and Cdk5 activity. Our results indicate that tumor necrosis factor-alpha (TNF-alpha) activates p35 promoter activity in a dose- and time-dependent manner and concomitantly up-regulates Cdk5 activity. Because TNF-alpha is known to activate ERK1/2, p38 MAPK, JNK, and NF-kappa B signaling pathways, we examined their involvement in the activation of p35 promoter activity. MEK inhibitor, which inhibits ERK activation, decreased p35 promoter activity, whereas the inhibitors of p38 MAPK, JNK, and NF-kappa B increased p35 promoter activity, indicating that these pathways regulate p35 expression differently. The mRNA and protein levels of Egr-1, a transcription factor, were increased by TNF-alpha treatment, and this increase was dependent on ERK signaling. In a mouse model of inflammation-induced pain in which carrageenan injection into the hind paw causes hypersensitivity to heat stimuli, TNF-alpha mRNA was increased at the site of injection. These findings suggest that TNF-alpha-mediated regulation of Cdk5 activity plays an important role in inflammation-induced pain signaling.
C1 [Kulkarni, Ashok B.] NIH, LCDB, NIDCR, Funct Gen Sect, Bethesda, MD 20892 USA.
[Keller, Jason; Iadarola, Michael J.] NIH, Neurobiol & Pain Therapeut Sect, NIDCR, Bethesda, MD 20892 USA.
[Rudrabhatla, Parvathi; Pant, Harish C.] NIH, Neurochem Lab, NINDS, Bethesda, MD 20892 USA.
RP Kulkarni, AB (reprint author), NIH, LCDB, NIDCR, Funct Gen Sect, 30 Convent Dr,Bldg 30,Rm 130,MSC 4395, Bethesda, MD 20892 USA.
EM ak40m@nih.gov
RI utreras, elias/I-1038-2013
OI utreras, elias/0000-0002-1004-0466
FU National Institutes of Health; Division of Intramural Research of NIDCR;
NINDS
FX This work was supported, in whole or in part, by the National Institutes
of Health, Division of Intramural Research of NIDCR and NINDS. The costs
of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 46
TC 47
Z9 47
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 23
PY 2009
VL 284
IS 4
BP 2275
EP 2284
DI 10.1074/jbc.M805052200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 395TE
UT WOS:000262545600037
PM 19049962
ER
PT J
AU Martin, B
Brenneman, R
Golden, E
Walent, T
Becker, KG
Prabhu, VV
Wood, W
Ladenheim, B
Cadet, JL
Maudsley, S
AF Martin, Bronwen
Brenneman, Randall
Golden, Erin
Walent, Tom
Becker, Kevin G.
Prabhu, Vinayakumar V.
Wood, William, III
Ladenheim, Bruce
Cadet, Jean-Lud
Maudsley, Stuart
TI Growth Factor Signals in Neural Cells COHERENT PATTERNS OF INTERACTION
CONTROL MULTIPLE LEVELS OF MOLECULAR AND PHENOTYPIC RESPONSES
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GENE SET ENRICHMENT; ALPHA-B-CRYSTALLIN; PHEOCHROMOCYTOMA CELLS;
NEURONAL DIFFERENTIATION; TYROSINE KINASES; PC12 CELLS; ACTIVATION;
EXPRESSION; SHC; PROTEINS
AB Individual neurons express receptors for several different growth factors that influence the survival, growth, neurotransmitter phenotype, and other properties of the cell. Although there has been considerable progress in elucidating the molecular signal transduction pathways and physiological responses of neurons and other cells to individual growth factors, little is known about if and how signals from different growth factors are integrated within a neuron. In this study, we determined the interactive effects of nerve growth factor, insulin-like growth factor 1, and epidermal growth factor on the activation status of downstream kinase cascades and transcription factors, cell survival, and neurotransmitter production in neural cells that express receptors for all three growth factors. We document considerable differences in the quality and quantity of intracellular signaling and eventual phenotypic responses that are dependent on whether cells are exposed to a single or multiple growth factors. Dual stimulations that generated the greatest antagonistic or synergistic actions, compared with a theoretically neutral summation of their two activities, yielded the largest eventual change of neuronal phenotype indicated by the ability of the cell to produce norepinephrine or resist oxidative stress. Combined activation of insulin-like growth factor 1 and epidermal growth factor receptors was particularly notable for antagonistic interactions at some levels of signal transduction and norepinephrine production, but potentiation at other levels of signaling and cytoprotection. Our findings suggest that in true physiological settings where multiple growth factors are present, activation of one receptor type may result in molecular and phenotypic responses that are different from that observed in typical experimental paradigms in which cells are exposed to only a single growth factor at a time.
C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Ladenheim, Bruce; Cadet, Jean-Lud] Natl Inst Drug Abuse, Mol Psychiat Branch, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Neurosci Lab, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
OI Becker, Kevin/0000-0002-6794-6656
FU National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health (Intramural Research Program of the NIA). The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 58
TC 22
Z9 22
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 23
PY 2009
VL 284
IS 4
BP 2493
EP 2511
DI 10.1074/jbc.M804545200
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 395TE
UT WOS:000262545600056
PM 19038969
ER
PT J
AU Sarafianos, SG
Marchand, B
Das, K
Himmel, DM
Parniak, MA
Hughes, SH
Arnold, E
AF Sarafianos, Stefan G.
Marchand, Bruno
Das, Kalyan
Himmel, Daniel M.
Parniak, Michael A.
Hughes, Stephen H.
Arnold, Eddy
TI Structure and Function of HIV-1 Reverse Transcriptase: Molecular
Mechanisms of Polymerization and Inhibition
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE polymerase structure and mechanism; AIDS; drug resistance; drug design;
ribonuclease H
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNASE-H DOMAIN; HIGH-LEVEL RESISTANCE;
DEPENDENT PRIMER UNBLOCKING; HIGH-RESOLUTION STRUCTURES; POLYMERASE
ACTIVE-SITE; ATP-MEDIATED EXCISION; STRAND DNA-SYNTHESIS;
RIBONUCLEASE-H; DRUG-RESISTANCE
AB The rapid replication of HIV-1 and the errors made during viral replication cause the virus to evolve rapidly in patients, making the problems of vaccine development and drug therapy particularly challenging. In the absence of an effective vaccine, drugs are the only useful treatment. Anti-HIV drugs work; so far drug therapy has saved more than three million years of life. Unfortunately, HIV-1 develops resistance to all of the available drugs. Although a number of useful anti-HIV drugs have been approved for use in patients, the problems associated with drug toxicity and the development of resistance means that the search for new drugs is an ongoing process. The three viral enzymes, reverse transcriptase (RT), integrase (IN), and protease (PR) are all good drug targets. Two distinct types of RT inhibitors, both of which block the polymerase activity of RT, have been approved to treat HIV-1. infections, nucleoside analogs (NRTIs) and nonnucleosides (NNRTIs), and there are promising leads for compounds that either block the RNase H activity or block the polymerase in other ways. A better understanding of the structure and function(s) of RT and of the mechanism(s) of inhibition can be used to generate better drugs; in particular, drugs that are effective against the current drug-resistant strains of HIV-1. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Das, Kalyan; Himmel, Daniel M.; Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Das, Kalyan; Himmel, Daniel M.; Arnold, Eddy] Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA.
[Sarafianos, Stefan G.; Marchand, Bruno] Univ Missouri, Christopher Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA.
[Parniak, Michael A.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA.
[Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
EM arnold@cabm.rutgers.edu
OI Sarafianos, Stefan G/0000-0002-5840-154X
FU NIH [A1076119, AT079801, A1074389, AI27690, P01 GM 066671]; amfAR
Mathilde Kim Fellowship grant; Intramural Research Program of NIH; NCI;
Center for Cancer Research; NIGMS; NTH [AI060452, AI73975, AI076119,
AI07980]
FX S.G.S. acknowledges support by NIH (grants A1076119, AT079801, and
A1074389). Support for B.M. comes from an amfAR Mathilde Kim Fellowship
grant. S.H.H. was supported by the Intramural Research Program of NIH,
NCI, Center for Cancer Research, and NIGMS. M.A.R was supported by NTH
grants AI060452, AI73975, AI076119, AI07980. E.A. is grateful for
support from NIH (grants AI27690 MERIT Award and P01 GM 066671).
NR 164
TC 204
Z9 209
U1 4
U2 50
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 JAN 23
PY 2009
VL 385
IS 3
BP 693
EP 713
DI 10.1016/j.jmb.2008.10.071
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 402HG
UT WOS:000263004200001
PM 19022262
ER
PT J
AU Kelly-Hope, LA
McKenzie, FE
AF Kelly-Hope, Louise A.
McKenzie, F. Ellis
TI The multiplicity of malaria transmission: a review of entomological
inoculation rate measurements and methods across sub-Saharan Africa
SO MALARIA JOURNAL
LA English
DT Review
ID LINKED-IMMUNOSORBENT-ASSAY; PLASMODIUM-FALCIPARUM TRANSMISSION; SAMPLING
ANOPHELINE MOSQUITOS; HUMAN LANDING CATCH; CONTROL LIGHT TRAP; WESTERN
KENYA; AFROTROPICAL ANOPHELES; SPOROZOITE DETECTION; HOLOENDEMIC AREA;
FIELD-EVALUATION
AB Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, most of them in Africa. It is transmitted by a range of Anopheles mosquitoes and the risk of disease varies greatly across the continent. The "entomological inoculation rate" is the commonly-used measure of the intensity of malaria transmission, yet the methods used are currently not standardized, nor do they take the ecological, demographic, and socioeconomic differences across populations into account. To better understand the multiplicity of malaria transmission, this study examines the distribution of transmission intensity across sub-Saharan Africa, reviews the range of methods used, and explores ecological parameters in selected locations. It builds on an extensive geo-referenced database and uses geographical information systems to highlight transmission patterns, knowledge gaps, trends and changes in methodologies over time, and key differences between land use, population density, climate, and the main mosquito species. The aim is to improve the methods of measuring malaria transmission, to help develop the way forward so that we can better assess the impact of the large-scale intervention programmes, and rapid demographic and environmental change taking place across Africa.
C1 [Kelly-Hope, Louise A.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.
[Kelly-Hope, Louise A.; McKenzie, F. Ellis] Natl Inst Hlth, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD USA.
RP Kelly-Hope, LA (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.
EM Kelly-Hope@liverpool.ac.uk; mckenzel@mail.nih.gov
NR 88
TC 80
Z9 81
U1 1
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD JAN 23
PY 2009
VL 8
AR 19
DI 10.1186/1475-2875-8-19
PG 16
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 424NQ
UT WOS:000264573800001
PM 19166589
ER
PT J
AU Mitchell, K
Yang, HYT
Berk, JD
Tran, JH
Iadarola, MJ
AF Mitchell, K.
Yang, H. -Y. T.
Berk, J. D.
Tran, J. H.
Iadarola, M. J.
TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN THE CHOROID PLEXUS: A POTENTIAL
LINK BETWEEN VASCULAR PRO-INFLAMMATORY MEDIATORS AND THE CNS DURING
PERIPHERAL TISSUE INFLAMMATION
SO NEUROSCIENCE
LA English
DT Article
DE BBB; BCSFB; ccl2; cox-2; cytokines; glial cells
ID BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR;
RAT-BRAIN; SPINAL-CORD; MICROGLIAL ACTIVATION; CEREBROSPINAL-FLUID;
PROSTAGLANDIN E-2; FREUNDS-ADJUVANT; GLIAL ACTIVATION
AB During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCPA protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared with other rat CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the nuclear factor-kappa B (NF-kappa B) signaling cascade including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta) and inhibitor of kappa B alpha (I kappa B alpha) in choroid tissue. Given that we also detected increased levels of MCPA protein by ELISA, we sought to identify potential downstream targets of MCPA and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS. Published by Elsevier Ltd on behalf of IBRO.
C1 [Mitchell, K.; Yang, H. -Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Dept Hlth & Human Serv, Bldg 49,Room 1C20,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA.
EM miadarola@dir.nidcr.nih.gov
FU Intramural Research Program; NIDCR; NIH; DHHS
FX This research was supported by the Intramural Research Program, NIDCR,
NIH, DHHS.
NR 46
TC 25
Z9 26
U1 0
U2 3
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 JAN 23
PY 2009
VL 158
IS 2
BP 885
EP 895
DI 10.1016/j.neuroscience.2008.10.047
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 401RP
UT WOS:000262959900051
PM 19032979
ER
PT J
AU Sabado, RL
Kavanagh, DG
Kaufmann, DE
Fru, K
Babcock, E
Rosenberg, E
Walker, B
Lifson, J
Bhardwaj, N
Larsson, M
AF Sabado, Rachel Lubong
Kavanagh, Daniel G.
Kaufmann, Daniel E.
Fru, Karlhans
Babcock, Ethan
Rosenberg, Eric
Walker, Bruce
Lifson, Jeffrey
Bhardwaj, Nina
Larsson, Marie
TI In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses,
Revealing Rapid Loss of Virus Reactive CD4(+) T Cells in Acute HIV-1
Infection
SO PLOS ONE
LA English
DT Article
AB Background: The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission.
Methodology: The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited.
Findings: Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naive T cells. Responses included several CD4(+) and CD8(+) T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4(+) T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4(+) T cell depletion which renders the newly activated HIV-specific CD4(+) T cells prime targets for elimination.
Conclusion: Our studies highlight the ability of DCs to efficiently prime naive T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
C1 [Babcock, Ethan; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10003 USA.
[Kavanagh, Daniel G.; Kaufmann, Daniel E.; Rosenberg, Eric; Walker, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, PARC, Charlestown, MA USA.
[Lifson, Jeffrey] NCI, NIH, SAIC Fredrick Inc, Frederick, MD USA.
[Fru, Karlhans; Larsson, Marie] Linkoping Univ, Dept Clin & Expt Med, S-58183 Linkoping, Sweden.
RP Sabado, RL (reprint author), NYU, Sch Med, New York, NY 10003 USA.
EM marla@imk.liu.se
FU The Swedish Research Council; The Swedish, Physicians against AIDS
research Foundation; The Swedish International Development Cooperation
Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University hospital
research Fund; C ALF; The Swedish Society of Medicine; Emerald
Foundation; Burroughs Wellcome; Elizabeth Glaser Pediatric AIDS
Foundation; Bill and Melinda Gates Foundation; Center for HIV/AIDS
Vaccine Initiative (CHAVI); NIH [AI52731, AI55274, AI61684, AI57127,
AI44628]; National Cancer Institute, National Institutes of Health
[N01-CO-12400]
FX All below funders have provided funding for performing this study. This
work has been supported by grants through: ML: AI52731, The Swedish
Research Council, The Swedish, Physicians against AIDS research
Foundation, The Swedish International Development Cooperation Agency;
SIDA SARC, VINNMER for Vinnova, Linkoping University hospital research
Fund, C ALF, and The Swedish Society of Medicine. NB: Emerald
Foundation, Burroughs Wellcome, Elizabeth Glaser Pediatric AIDS
Foundation, Bill and Melinda Gates Foundation and the Center for
HIV/AIDS Vaccine Initiative (CHAVI) and NIH grants AI52731, AI55274,
AI61684, AI57127, and AI44628. JL: with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
N01-CO-12400. The content of this publication does not necessarily
reflect the views of 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 63
TC 24
Z9 24
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 JAN 23
PY 2009
VL 4
IS 1
AR e4256
DI 10.1371/journal.pone.0004256
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437JD
UT WOS:000265482400004
ER
PT J
AU Yong, ASM
Keyvanfar, K
Hensel, N
Eniafe, R
Savani, BN
Berg, M
Lundqvist, A
Adams, S
Sloand, EM
Goldman, JM
Childs, R
Barrett, AJ
AF Yong, Agnes S. M.
Keyvanfar, Keyvan
Hensel, Nancy
Eniafe, Rhoda
Savani, Bipin N.
Berg, Maria
Lundqvist, Andreas
Adams, Sharon
Sloand, Elaine M.
Goldman, John M.
Childs, Richard
Barrett, A. John
TI Primitive quiescent CD34(+) cells in chronic myeloid leukemia are
targeted by in vitro expanded natural killer cells, which are
functionally enhanced by bortezomib
SO BLOOD
LA English
DT Article
ID CHRONIC MYELOGENOUS LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; DONOR
LYMPHOCYTE INFUSIONS; APOPTOSIS-INDUCING LIGAND; T-CELLS; CHRONIC-PHASE;
PROGENITOR-CELLS; STEM-CELLS; PROTEASOME INHIBITION; TUMOR-CYTOTOXICITY
AB Primitive quiescent CD34(+) chronic myeloid leukemia (CML) cells are more biologically resistant to tyrosine kinase inhibitors than their cycling counterparts; however, graft-versus-leukemia (GVL) effects after allogeneic stem cell transplantation (SCT) probably eliminate even these quiescent cells in long-term surviving CML transplant recipients. We studied the progeny of CD34(+) cells from CML patients before SCT, which were cultured 4 days in serum-free media with hematopoietic growth factors. BCR-ABL expression was similar in both cycling and quiescent noncycling CD34(+) populations. Quiescent CD34(+) cells from CML patients were less susceptible than their cycling CD34(+) and CD34(-) counterparts to lysis by natural killer (NK) cells from their HLA-identical sibling donors. Compared with cycling populations, quiescent CD34(+) CML cells had higher surface expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4 and DR5. Bortezomib upregulated TRAIL receptor expression on quiescent CD34(+) CML cells, and further enhanced their susceptibility to cytotoxicity by in vitro expanded donor NK cells. These results suggest that donor-derived NK cell-mediated GVL effects may be improved by sensitizing residual quiescent CML cells to NK-cell cytotoxicity after SCT. Such treatment, as an adjunct to donor lymphocyte infusions and pharmacologic therapy, may reduce the risk of relapse in CML patients who require treatment by SCT. (Blood. 2009;113:875-882)
C1 [Yong, Agnes S. M.; Keyvanfar, Keyvan; Hensel, Nancy; Eniafe, Rhoda; Savani, Bipin N.; Berg, Maria; Lundqvist, Andreas; Adams, Sharon; Sloand, Elaine M.; Goldman, John M.; Childs, Richard; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Yong, ASM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5140,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA.
EM yonga@nhlbi.nih.gov
OI Lundqvist, Andreas/0000-0002-9709-2970
FU National Institutes of Health
FX The authors thank Dr Heather Jorgensen and Prof Tessa Holyoake from the
Section of Experimental Hematology, University of Glasgow, United
Kingdom, for technical advice on quiescent CML CD34+ cell
cultures, and Dr Giuseppe Sconocchia from the National Research Council
Institute for Organ Transplantation and Immunocitology, Rome, Italy, for
advice on NK-cell cultures. The authors are grateful to Dr Colin Wu from
the Office of Biostatistics Research at the National Heart, Lung, and
Blood Institute (NHLBI) for providing formal statistical review.; This
research was supported by the Intramural Research Program of the
National Institutes of Health at the NHLBI.
NR 45
TC 37
Z9 37
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JAN 22
PY 2009
VL 113
IS 4
BP 875
EP 882
DI 10.1182/blood-2008-05-158253
PG 8
WC Hematology
SC Hematology
GA 397EW
UT WOS:000262646200016
PM 18922853
ER
PT J
AU Johnson, AD
O'Donnell, CJ
AF Johnson, Andrew D.
O'Donnell, Christopher J.
TI An Open Access Database of Genome-wide Association Results
SO BMC MEDICAL GENETICS
LA English
DT Article
ID CANDIDATE GENES; SUSCEPTIBILITY; DISEASE; POLYMORPHISMS; GENETICS;
HAPMAP; OAS-1; LOCI; SNPS; TOOL
AB Background: The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results.
Methods: We collected available results from 118 GWAS articles into a database of 56,411 significant SNP-phenotype associations and accompanying information, making this database freely available here. In doing so, we met and describe here a number of challenges to creating an open access database of GWAS results. Through preliminary analyses and characterization of available GWAS, we demonstrate the potential to gain new insights by querying a database across GWAS.
Results: Using a genomic bin-based density analysis to search for highly associated regions of the genome, positive control loci (e. g., MHC loci) were detected with high sensitivity. Likewise, an analysis of highly repeated SNPs across GWAS identified replicated loci (e. g., APOE, LPL). At the same time we identified novel, highly suggestive loci for a variety of traits that did not meet genome-wide significant thresholds in prior analyses, in some cases with strong support from the primary medical genetics literature (SLC16A7, CSMD1, OAS1), suggesting these genes merit further study. Additional adjustment for linkage disequilibrium within most regions with a high density of GWAS associations did not materially alter our findings. Having a centralized database with standardized gene annotation also allowed us to examine the representation of functional gene categories (gene ontologies) containing one or more associations among top GWAS results. Genes relating to cell adhesion functions were highly over-represented among significant associations (p < 4.6 x 10(-14)), a finding which was not perturbed by a sensitivity analysis.
Conclusion: We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting.
C1 [Johnson, Andrew D.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
EM johnsonad2@nhlbi.nih.gov; odonnellc@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013
FU NIH/NHLBI [N01-HC-25195]
FX We would like to acknowledge the many thousands of international,
anonymous participants of the GWAS included here for their contribution
to human genetics. We thank Wolfgang Lieb, MD and Raghava Velagaleti, MD
for their assistance as QC reviewers of the dataset. ADJ was supported
by an intramural NHLBI IRTA fellowship award. This project was supported
in part by the NHLBI's Framingham Heart Study (NIH/NHLBI Contract
N01-HC-25195). We thank Teri Manolio, MD PhD for her comments on the
manuscript.
NR 33
TC 173
Z9 180
U1 2
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JAN 22
PY 2009
VL 10
AR 6
DI 10.1186/1471-2350-10-6
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 418MS
UT WOS:000264152900002
PM 19161620
ER
PT J
AU Hickman, HD
Bennink, JR
Yewdell, JW
AF Hickman, Heather D.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Caught in the Act: Intravital Multiphoton Microscopy of Host-Pathogen
Interactions
SO CELL HOST & MICROBE
LA English
DT Article
ID GREEN FLUORESCENT PROTEIN; CD8(+) T-CELLS; CONDITIONAL MACROPHAGE
ABLATION; INTERACTIONS IN-VIVO; DENDRITIC CELLS; LYMPH-NODES; REAL-TIME;
INFECTION; GENE; DIFFERENTIATION
AB Intravital multiphoton microscopy provides a unique opportunity to discover and characterize biological phenomena in the natural context of living organisms. Here we provide an overview of multiphoton microscopy with particular attention to its application for studying host-pathogen interactions.
C1 [Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Hickman, HD (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM hhickman@mail.nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
FU Intramural NIH HHS [Z01 AI001053-01]
NR 49
TC 18
Z9 19
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JAN 22
PY 2009
VL 5
IS 1
BP 13
EP 21
DI 10.1016/j.chom.2008.12.007
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 400RG
UT WOS:000262885700005
PM 19154984
ER
PT J
AU Balasubramanian, R
Raghavan, B
Begaye, A
Sackett, DL
Fecik, RA
AF Balasubramanian, Ranganathan
Raghavan, Bhooma
Begaye, Adrian
Sackett, Dan L.
Fecik, Robert A.
TI Total Synthesis and Biological Evaluation of Tubulysin U, Tubulysin V,
and Their Analogues
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL ANTICANCER; MYXOBACTERIA; POLYMERIZATION; TUBULIN
AB A stercoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epitubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition.
C1 [Balasubramanian, Ranganathan; Raghavan, Bhooma; Fecik, Robert A.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
[Begaye, Adrian; Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
RP Fecik, RA (reprint author), Univ Minnesota, Dept Med Chem, 308 Harvard St SE,8-101 Weaver Densford Hall, Minneapolis, MN 55455 USA.
EM fecik001@umn.edu
FU American Cancer Society [RSG-05-105-01-CDD]; National Institute of Child
Health and Human Development, NIH; University of Minnesota Medical
School, NSF [BIR-961577]; Minnesota Medical Foundation
FX This work was generously supported by the American Cancer Society, Grant
RSG-05-105-01-CDD (to R.A.F.) and was supported in part by intramural
funds from the National Institute of Child Health and Human Development,
NIH. Funding for NMR instrumentation in the Department of Biochemistry,
Molecular Biology, and Biophysics was provided by the University of
Minnesota Medical School, NSF (Grant BIR-961577), and the Minnesota
Medical Foundation.
NR 20
TC 28
Z9 28
U1 0
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JAN 22
PY 2009
VL 52
IS 2
BP 238
EP 240
DI 10.1021/jm8013579
PG 3
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 395KD
UT WOS:000262522100003
PM 19102699
ER
PT J
AU Leopold, DA
AF Leopold, David A.
TI NEUROSCIENCE Pre-emptive blood flow
SO NATURE
LA English
DT Editorial Material
ID NEURAL BASIS; FMRI; SIGNALS
C1 [Leopold, David A.] NIH, Neuropsychol Lab, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA.
RP Leopold, DA (reprint author), NIH, Neuropsychol Lab, Unit Cognit Neurophysiol & Imaging, Bldg 10, Bethesda, MD 20892 USA.
EM leopoldd@mail.nih.gov
OI Leopold, David/0000-0002-1345-6360
FU Intramural NIH HHS [Z01 MH002896-01, Z01 MH002899-01, Z01 MH002838-04]
NR 9
TC 13
Z9 13
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JAN 22
PY 2009
VL 457
IS 7228
BP 387
EP 388
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 395JA
UT WOS:000262519200025
PM 19158777
ER
PT J
AU Carim-Todd, L
Bath, KG
Fulgenzi, G
Yanpallewar, S
Jing, DQ
Barrick, CA
Becker, J
Buckley, H
Dorsey, SG
Lee, FS
Tessarollo, L
AF Carim-Todd, Laura
Bath, Kevin G.
Fulgenzi, Gianluca
Yanpallewar, Sudhirkumar
Jing, Deqiang
Barrick, Colleen A.
Becker, Jodi
Buckley, Hannah
Dorsey, Susan G.
Lee, Francis S.
Tessarollo, Lino
TI Endogenous Truncated TrkB.T1 Receptor Regulates Neuronal Complexity and
TrkB Kinase Receptor Function In Vivo
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE TrkB.T1; BDNF; mouse; anxiety; neurites; amygdala
ID NEUROTROPHIC FACTOR; NERVOUS-SYSTEM; FULL-LENGTH; CONDITIONAL DELETION;
SIGNAL-TRANSDUCTION; HUMAN-MEMORY; CELL-DEATH; RAT TRKC; BDNF;
HIPPOCAMPAL
AB Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific physiological functions and its effect on endogenous TrkB kinase signaling in vivo. We found that TrkB.T1-deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and long-term potentiation. In vivo reduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our results suggest that, at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.
C1 [Carim-Todd, Laura; Fulgenzi, Gianluca; Yanpallewar, Sudhirkumar; Barrick, Colleen A.; Becker, Jodi; Buckley, Hannah; Dorsey, Susan G.; Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Bath, Kevin G.; Jing, Deqiang; Lee, Francis S.] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA.
[Fulgenzi, Gianluca] Univ Marche, Dept Mol Pathol, I-60020 Ancona, Italy.
[Dorsey, Susan G.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
RP Tessarollo, L (reprint author), NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, 7th St,Bldg 560,Room 32-31D,POB B, Frederick, MD 21702 USA.
EM tessarol@mail.nih.gov
OI Fulgenzi, Gianluca/0000-0003-2646-7728
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research [MH060478, NS052819]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research, and NIH Grants MH060478 (K. G. B.) and NS052819 (F.
S. L.).
NR 53
TC 61
Z9 62
U1 1
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 21
PY 2009
VL 29
IS 3
BP 678
EP 685
DI 10.1523/JNEUROSCI.5060-08.2009
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 395TH
UT WOS:000262545900010
PM 19158294
ER
PT J
AU Kong, LL
Wang, XY
Choe, DW
Polley, M
Burnett, BG
Bosch-Marce, M
Griffin, JW
Rich, MM
Sumner, CJ
AF Kong, Lingling
Wang, Xueyong
Choe, Dong W.
Polley, Michelle
Burnett, Barrington G.
Bosch-Marce, Marta
Griffin, John W.
Rich, Mark M.
Sumner, Charlotte J.
TI Impaired Synaptic Vesicle Release and Immaturity of Neuromuscular
Junctions in Spinal Muscular Atrophy Mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE spinal muscular atrophy; motor neuron; neuromuscular junction; synapse;
synaptic vesicle; acetylcholine receptor
ID MOTOR-NEURON DISEASE; TO-EPSILON-SWITCH; MOUSE MODEL;
ACETYLCHOLINE-RECEPTOR; AXONAL DEGENERATION; TRANSMITTER RELEASE;
DETERMINING GENE; SKELETAL-MUSCLE; IN-VIVO; SMN
AB The motor neuron disease spinal muscular atrophy (SMA) causes profound muscle weakness that most often leads to early death. At autopsy, SMA is characterized by loss of motor neurons and muscle atrophy, but the initial cellular events that precipitate motor unit dysfunction and loss remain poorly characterized. Here, we examined the function and corresponding structure of neuromuscular junction (NMJ) synapses in a mouse model of severe SMA (hSMN2/delta7SMN/mSmn(-/-)). Surprisingly, most SMA NMJs remained innervated even late in the disease course; however they showed abnormal synaptic transmission. There was a two-fold reduction in the amplitudes of the evoked endplate currents (EPCs), but normal spontaneous miniature EPC (MEPC) amplitudes. These features in combination indicate reduced quantal content. SMA NMJs also demonstrated increased facilitation suggesting a reduced probability of vesicle release. By electron microscopy, we found a decreased density of synaptic vesicles that is likely to contribute to the reduced release probability. In addition to presynaptic defects, there were postsynaptic abnormalities. EPC and MEPC decay time constants were prolonged because of a slowed switch from the fetal acetylcholine receptor (AChR) gamma-subunit to the adult epsilon-subunit. There was also reduced size of AChR clusters and small myofibers, which expressed an immature pattern of myosin heavy chains. Together these results indicate that impaired synaptic vesicle release at NMJs in severe SMA is likely to contribute to failed postnatal maturation of motor units and muscle weakness.
C1 [Kong, Lingling; Choe, Dong W.; Polley, Michelle; Bosch-Marce, Marta; Griffin, John W.; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Wang, Xueyong; Rich, Mark M.] Wright State Univ, Dept Neurol Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA.
[Burnett, Barrington G.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Sumner, CJ (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St,Meyer 5-119B, Baltimore, MD 21287 USA.
EM csumner1@jhmi.edu
FU Robert Packard Center; National Institute of Neurological Disorders and
Stroke (NINDS) [K22-NS0048199-01, P01NS057228]; Families of Spinal
Muscular Atrophy Grant; Howard Hughes Medical Institute Physician
Scientist Award
FX L. K. was supported by funding from the Robert Packard Center for ALS
Research. C.J.S. was supported by a National Institute of Neurological
Disorders and Stroke (NINDS) Career Transition Award (K22-NS0048199-01),
Families of Spinal Muscular Atrophy Grant, and Howard Hughes Medical
Institute Physician Scientist Award. M. M. R. was supported by NINDS
Grant P01NS057228. B. G. B. was supported by an NINDS Competitive
Fellowship Award. We thank Carol Rubright for EM support and Norihiro
Yumoto for providing the AChR gamma antibody.
NR 50
TC 194
Z9 195
U1 1
U2 15
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 JAN 21
PY 2009
VL 29
IS 3
BP 842
EP 851
DI 10.1523/JNEUROSCI.4434-08.2009
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 395TH
UT WOS:000262545900024
PM 19158308
ER
PT J
AU Zhu, BP
Li, DD
Zhou, QF
Shi, J
Shung, KK
AF Zhu, B. P.
Li, D. D.
Zhou, Q. F.
Shi, J.
Shung, K. K.
TI Piezoelectric PZT thick films on LaNiO3 buffered stainless steel foils
for flexible device applications
SO JOURNAL OF PHYSICS D-APPLIED PHYSICS
LA English
DT Article
ID PULSED-LASER DEPOSITION; DIELECTRIC-PROPERTIES; ELECTRICAL-PROPERTIES;
AEROSOL DEPOSITION; METAL FOILS
AB In this paper, we report on 4.5 mu m piezoelectric Pb(Zr0.52Ti0.48)O-3 (PZT) thick films deposited on flexible stainless steel (SS) foils with LaNiO3 (LNO) buffer layers using a ceramic powder/sol-gel solution modified composite method. The polycrystalline thick films show a hysteresis loop at an applied electric field of 900 kV cm(-1) with remanent polarization and coercive electric field values of 27 mu C cm(-2) and 85 kV cm(-1), respectively. At 1 kHz, the dielectric constant is 653 and the dielectric loss is 0.052. The leakage current density of the film is lower than 1.55 x 10(-5) A cm(-2) over the range of 0 to +/-150V. The conduction current shows ohmic behaviour at a low electric field and space-charge-limited current characteristics at a high electric field.
C1 [Zhu, B. P.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Zhu, B. P.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Zhu, B. P.; Shi, J.] Wuhan Univ, Dept Phys, Wuhan 430072, Peoples R China.
[Zhu, B. P.; Shi, J.] Wuhan Univ, Key Lab Acoust & Photon Mat & Devices, Minist Educ, Wuhan 430072, Peoples R China.
[Li, D. D.] Shanghai Jiao Tong Univ, Sch Mat Sci & Engn, Shanghai 200240, Peoples R China.
RP Zhou, QF (reprint author), Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM qifazhou@usc.edu
RI Li, Dongdong/A-2703-2011
OI Li, Dongdong/0000-0003-3219-181X
FU NIH [P41-EB2182]; Chinese Scholarship Council, China
FX The authors acknowledge the support of the NIH grant P41-EB2182. B P Zhu
is supported by the Chinese Scholarship Council, China.
NR 20
TC 5
Z9 5
U1 0
U2 10
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0022-3727
J9 J PHYS D APPL PHYS
JI J. Phys. D-Appl. Phys.
PD JAN 21
PY 2009
VL 42
IS 2
AR 025504
DI 10.1088/0022-3727/42/2/025504
PG 4
WC Physics, Applied
SC Physics
GA 385WB
UT WOS:000261843200035
ER
PT J
AU Greene, MH
Mai, PL
AF Greene, Mark H.
Mai, Phuong L.
TI What Have We Learned from Risk-Reducing Salpingo-oophorectomy?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID PROPHYLACTIC OOPHORECTOMY; PERCEIVED AMBIGUITY; MUTATION CARRIERS;
CANCER PREVENTION; OVARIAN-CANCER; RECOMMENDATIONS; PERCEPTIONS;
CARCINOMA; BRCA1
C1 [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Greene, MH (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room EPS 7032, Rockville, MD 20852 USA.
EM greenem@mail.nih.gov
NR 10
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN 21
PY 2009
VL 101
IS 2
BP 70
EP 71
DI 10.1093/jnci/djn476
PG 2
WC Oncology
SC Oncology
GA 398GU
UT WOS:000262721400001
PM 19141782
ER
PT J
AU Franklin, SS
Lopez, VA
Wong, ND
Mitchell, GF
Larson, MG
Vasan, RS
Levy, D
AF Franklin, Stanley S.
Lopez, Victor A.
Wong, Nathan D.
Mitchell, Gary F.
Larson, Martin G.
Vasan, Ramachandran S.
Levy, Daniel
TI Single Versus Combined Blood Pressure Components and Risk for
Cardiovascular Disease The Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE blood pressure; cardiovascular diseases; hypertension; mean arterial
pressure; pulse pressure
ID PULSE PRESSURE; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; MORTALITY;
ASSOCIATION; PREDICTOR; PULSATILE; INDEXES; HEALTH; ADULTS
AB Background-The utility of single versus combined blood pressure (BP) components in predicting cardiovascular disease (CVD) events is not established. We compared systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP) and mean arterial pressure (MAP) combined and each of these 4 BP components alone in predicting CVD events.
Methods and Results-In participants in the original (n=4760) and offspring (n=4897) Framingham Heart Study who were free of CVD events and BP-lowering therapy, 1439 CVD events occurred over serial 4-year intervals from 1952 to 2001. In pooled logistic regression with the use of BP categories, combining SBP with DBP and PP with MAP improved model fit compared with individual BP components (P<0.05 to P<0.0001). Significant interactions were noted between SBP and DBP (P=0.02) and between PP and MAP (P=0.01) in their respective multivariable models. Models with continuous variables for SBP+DBP and PP+MAP proved identical in predicting CVD events (Akaike Information Criteria = 10 625 for both). Addition of a quadratic DBP(2) term to DBP and SBP further improved fit (P=0.0016).
Conclusions-Combining PP with MAP and SBP with DBP produced models that were superior to single BP components for predicting CVD, and the extent of CVD risk varied with the level of each BP component. The combination of PP+MAP (unlike SBP+DBP) has a monotonic relation with risk and may provide greater insight into hemodynamics of altered arterial stiffness versus impaired peripheral resistance but is not superior to SBP+DBP in predicting CVD events. (Circulation. 2009;119:243-250.)
C1 [Franklin, Stanley S.; Lopez, Victor A.; Wong, Nathan D.] Univ Calif Irvine, Dept Med, Heart Dis Prevent Program, Irvine, CA 92697 USA.
[Larson, Martin G.; Vasan, Ramachandran S.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Med Ctr, Div Cardiol, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Franklin, SS (reprint author), Univ Calif Irvine, Dept Med, Heart Dis Prevent Program, C240 Med Sci, Irvine, CA 92697 USA.
EM ssfranklinmd@earthlink.net
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[N01-HC-25195, 2K24HL04334]
FX The Framingham Heart study is supported by National Institutes of
Health/National Heart, Lung, and Blood Institute contract N01-HC-25195.
Dr Vasan was supported in part by National Institutes of Health/National
Heart, Lung, and Blood Institute contract 2K24HL04334.
NR 36
TC 114
Z9 126
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JAN 20
PY 2009
VL 119
IS 2
BP 243
EP U69
DI 10.1161/CIRCULATIONAHA.108.797936
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 396XL
UT WOS:000262625300009
PM 19118251
ER
PT J
AU Garg, PK
Liu, K
Tian, L
Guralnik, JM
Ferrucci, L
Criqui, MH
Tan, J
McDermott, MM
AF Garg, Parveen K.
Liu, Kiang
Tian, Lu
Guralnik, Jack M.
Ferrucci, Luigi
Criqui, Michael H.
Tan, Jin
McDermott, Mary M.
TI Physical Activity During Daily Life and Functional Decline in Peripheral
Arterial Disease
SO CIRCULATION
LA English
DT Article
DE claudication; exercise; peripheral vascular disease; risk factors
ID ANKLE BRACHIAL INDEX; LOWER-EXTREMITY FUNCTION; CHRONIC HEART-FAILURE;
INTERMITTENT CLAUDICATION; CALTRAC ACCELEROMETER; EXERCISE CAPACITY;
OCCLUSIVE DISEASE; LONGITUDINAL DATA; 6-MINUTE WALK; LEG SYMPTOMS
AB Background-Few modifiable behaviors have been identified that are associated with slower rates of functional decline in persons with lower-extremity peripheral arterial disease. We determined whether higher levels of physical activity during daily life are associated with less functional decline in persons with peripheral arterial disease.
Methods and Results-The study population included 203 peripheral arterial disease participants who underwent vertical accelerometer-measured physical activity continuously over 7 days and were followed up annually for up to 4 years (mean, 33.6 months). Outcomes were average annual changes in 6-minute walk performance, usual-paced and fast-paced 4-m walking velocity, and the short performance physical battery. Analyses were adjusted for age, sex, race, comorbidities, body mass index, ankle brachial index, smoking, and walking exercise frequency. Higher baseline physical activity levels measured by a vertical accelerometer were associated with significantly less average annual decline in 6-minute walk performance (P for trend=0.010), fast-paced 4-m walking velocity (P for trend=0.002), and the short performance physical battery (P for trend=0.001). Compared with the lowest baseline quartile, those in the highest baseline quartile of physical activity had less annual decline in 6-minute walk performance (-50.82 versus -107.0 ft/y; P=0.019), fast-paced 4-m walking speed (-0.0034 versus -0.111 m . s(-1) . y (-)1; P = 0.002), and the short performance physical battery (-0.074 versus -0.829; P=0.005).
Conclusions-Higher physical activity levels during daily life are associated with less functional decline among people with peripheral arterial disease. These findings may be particularly important for the large number of peripheral arterial disease persons without access to supervised walking exercise programs. (Circulation. 2009;119:251-260.)
C1 [Garg, Parveen K.; Liu, Kiang; Tian, Lu; Tan, Jin; McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU Intramural NIH HHS [ZIA AG001056-02]
NR 48
TC 59
Z9 64
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JAN 20
PY 2009
VL 119
IS 2
BP 251
EP 260
DI 10.1161/CIRCULATIONAHA.108.791491
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 396XL
UT WOS:000262625300010
PM 19118256
ER
PT J
AU Mavrakis, M
Rikhy, R
Lippincott-Schwartz, J
AF Mavrakis, Manos
Rikhy, Richa
Lippincott-Schwartz, Jennifer
TI Plasma Membrane Polarity and Compartmentalization Are Established before
Cellularization in the Fly Embryo
SO DEVELOPMENTAL CELL
LA English
DT Article
ID DROSOPHILA EMBRYO; ACTIN POLYMERIZATION; EPITHELIAL POLARITY; MORPHOGEN
GRADIENT; TOLL GENE; PROTEIN; NUCLEAR; CELLS; EMBRYOGENESIS;
LOCALIZATION
AB Patterning in the Drosophila embryo requires local activation and dynamics of proteins in the plasma membrane (PM). We used in vivo fluorescence imaging to characterize the organization and diffusional properties of the PM in the early embryonic syncytium. Before cellularization, the PM is polarized into discrete domains having epithelial-like characteristics. One domain resides above individual nuclei and has apical-like characteristics, while the other domain is lateral to nuclei and contains markers associated with basolateral membranes and junctions. Pulse-chase photoconversion experiments show that molecules can diffuse within each domain but do not exchange between PM regions above adjacent nuclei. Drug-induced F-actin depolymerization disrupted both the apicobasal-like polarity and the diffusion barriers within the syncytial PM. These events correlated with perturbations in the spatial pattern of dorsoventral Toll signaling. We propose that epithelial-like properties and an intact F-actin network compartmentalize the PM and shape morphogen gradients in the syncytial embryo.
C1 NICHHD, NIH, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Mavrakis, M (reprint author), Univ Aix Marseille 2, CNRS, UMR6216, Inst Dev Biol Marseille Luminy, Parc Sci Luminy BP 907, F-13009 Marseille, France.
EM mavrakis@ibdml.univ-mrs.fr; jlippin@helix.nih.gov
RI Rikhy, Richa/J-4481-2012;
OI Rikhy, Richa/0000-0002-4262-0238
FU Intramural Research Program of the NIH; National Institute of Child
Health and Human Development
FX We thank the members of the Lippincott-Schwartz and Mary Lilly labs for
their supporl throughout this work, as well as Yannick Azou. Bernhard
Hampoelz, and Ldfc Le Goff for their valuable comments and helpful
discussions. We are especially grateful to Mary Lilly for providing us
with the facility for Drosophila work. This work was supported by the
Intramural Research Program of the NIH, National Institute of Child
Health and Human Development.
NR 43
TC 42
Z9 43
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD JAN 20
PY 2009
VL 16
IS 1
BP 93
EP 104
DI 10.1016/j.devcel.2008.11.003
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 398UR
UT WOS:000262757500013
PM 19154721
ER
PT J
AU Tsukasaki, K
Hermine, O
Bazarbachi, A
Ratner, L
Ramos, JC
Harrington, W
O'Mahony, D
Janik, JE
Bittencourt, AL
Taylor, GP
Yamaguchi, K
Utsunomiya, A
Tobinai, K
Watanabe, T
AF Tsukasaki, Kunihiro
Hermine, Olivier
Bazarbachi, Ali
Ratner, Lee
Ramos, Juan Carlos
Harrington, William, Jr.
O'Mahony, Deirdre
Janik, John E.
Bittencourt, Achilea L.
Taylor, Graham P.
Yamaguchi, Kazunari
Utsunomiya, Atae
Tobinai, Kensei
Watanabe, Toshiki
TI Definition, Prognostic Factors, Treatment, and Response Criteria of
Adult T-Cell Leukemia-Lymphoma: A Proposal From an International
Consensus Meeting
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the American-Society-of-Hematology
CY DEC 08-11, 2007
CL Atlanta, GA
SP Amer Soc Hematol
ID I-TRANSFORMED-CELLS; INTERFERON-ALPHA; CLINICAL-SIGNIFICANCE; WORLDWIDE
METAANALYSIS; ARSENIC TRIOXIDE; LEUKEMIA/LYMPHOMA; ZIDOVUDINE;
COMBINATION; INVOLVEMENT; EXPRESSION
AB Adult T-cell leukemia-lymphoma ( ATL) is a distinct peripheral T-lymphocytic malignancy associated with a retrovirus designated human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories: acute, lymphoma, chronic, and smoldering types. The chronic and smoldering subtypes are considered indolent and are usually managed with watchful waiting until disease progression, analogous to the management of some patients with chronic lymphoid leukemia (CLL) or other indolent histology lymphomas. Patients with aggressive ATL generally have a poor prognosis because of multidrug resistance of malignant cells, a large tumor burden with multiorgan failure, hypercalcemia, and/or frequent infectious complications as a result of a profound T-cell immunodeficiency. Under the sponsorship of the 13th International Conference on Human Retrovirology: HTLV, a group of ATL researchers joined to form a consensus statement based on established data to define prognostic factors, clinical subclassifications, and treatment strategies. A set of response criteria specific for ATL reflecting a combination of those for lymphoma and CLL was proposed. Clinical subclassification is useful but is limited because of the diverse prognosis among each subtype. Molecular abnormalities within the host genome, such as tumor suppressor genes, may account for these diversities. A treatment strategy based on the clinical subclassification and prognostic factors is suggested, including watchful waiting approach, chemotherapy, antiviral therapy, allogeneic hematopoietic stem-cell transplantation (alloHSCT), and targeted therapies.
C1 [Tsukasaki, Kunihiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Med & Hematol, Mol Med Unit,Atom Bomb Dis Inst, Nagasaki 8528523, Japan.
Univ Paris 05, Necker Hosp, Paris, France.
CNRS, UMR 8147, Paris, France.
Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon.
Washington Univ, St Louis, MO USA.
Natl Canc Inst, Bethesda, MD USA.
Univ Fed Bahia, BR-41170290 Salvador, BA, Brazil.
Univ London Imperial Coll Sci Technol & Med, London, England.
Univ Tokyo, Tokyo, Japan.
Natl Inst Infect Dis, Tokyo, Japan.
Natl Canc Ctr, Tokyo, Japan.
Imamura Bunin Hosp, Kagoshima, Japan.
RP Tsukasaki, K (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Med & Hematol, Mol Med Unit,Atom Bomb Dis Inst, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
EM tsukasak@net.nagasaki-u.ac.jp
FU Intramural NIH HHS
NR 61
TC 204
Z9 208
U1 0
U2 12
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2009
VL 27
IS 3
BP 453
EP 459
DI 10.1200/JCO.2008.18.2428
PG 7
WC Oncology
SC Oncology
GA 395CE
UT WOS:000262499100022
PM 19064971
ER
PT J
AU Wang, H
Iguchi, N
Rong, Q
Zhou, ML
Ogunkorode, M
Inoue, N
Pribitkin, EA
Bachnianov, AA
Margolskee, RF
Pfeifer, K
Huang, LQ
AF Wang, Hong
Iguchi, Naoko
Rong, Qi
Zhou, Minliang
Ogunkorode, Martina
Inoue, Niasashi
Pribitkin, Edmund A.
Bachnianov, Alexander A.
Margolskee, Robert F.
Pfeifer, Karl
Huang, Liquan
TI Expression of the Voltage-Gated Potassium Channel KCNQ1 in Mammalian
Taste Bud Cells and the Effect of Its Null-Mutation on Taste Preferences
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE cell turnover; human biopsy; co-expression; gene knockout
ID PUTATIVE PHEROMONE RECEPTORS; SWEET TASTE; ACTION-POTENTIALS; UMAMI
TASTE; K+ CHANNELS; TARGETED DISRUPTION; SIGNALING PATHWAYS; DEPENDENT
CURRENTS; CATION CHANNEL; T1R FAMILY
AB Vertebrate taste buds undergo continual cell turnover. To understand how the gustatory progenitor cells in the stratified lingual epithelium migrate and differentiate into different types of mature taste cells, we sought to identify genes that were selectively expressed in taste cells at different maturation stages. Here we report the expression of the voltage-gated potassium channel KCNQ1 in mammalian taste buds of mouse, rat, and human. Immunohistochemistry and nuclear staining showed that nearly all rodent and human taste cells express this channel. Double immunostaining with antibodies against type II and III taste cell markers validated the presence of KCNQ1 in these two types of cells. Co-localization studies with cytokeratin 14 indicated that KCNQ1 is also expressed in type IV basal precursor cells. Null mutation of the kcnq1 gene in mouse, however, did not alter the gross structure of taste buds or the expression of taste signaling molecules. Behavioral assays showed that the mutant mice display reduced preference to some umami substances, but not to any other taste compounds tested. Gustatory nerve recordings, however, were unable to detect any significant change in the integrated nerve responses of the mutant mice to umami stimuli. These results suggest that although it is expressed in nearly all taste bud cells, the function of KCNQ1 is not required for gross taste bud development or peripheral taste transduction pathways, and the reduced preference of kcnq1-null mice in the behavioral assays may be attributable to the deficiency in the central nervous system or other organs. J. Comp. Neurol. 512:384-398, 2009. (C) 2008 Wiley-Liss, Inc.
C1 [Wang, Hong; Iguchi, Naoko; Zhou, Minliang; Ogunkorode, Martina; Bachnianov, Alexander A.; Huang, Liquan] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
[Rong, Qi; Pfeifer, Karl] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
[Inoue, Niasashi] Tokyo Univ Pharm & Life Sci, Dept Life Sci, Tokyo, Japan.
[Pribitkin, Edmund A.] Thomas Jefferson Univ, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19107 USA.
[Margolskee, Robert F.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
RP Huang, LQ (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA.
EM Lhuang@monell.org
OI Bachmanov, Alexander/0000-0002-2861-3322; Pfeifer,
Karl/0000-0002-0254-682X
FU National Institutes of Health [R01 DC007487, R03 DC007974, R01 DC00882,
R01 DC003155]; National Science Foundation [DBJ-0216310]
FX Grant Sponsor: National Institutes of Health; Grant numbers: R01
DC007487 (to L.H.), R03 DC007974 (to H.W.), R01 DC00882 (toA.A.B.), R01
DC003155 (to R.F.M.); Grant sponsor: National Science Foundation; Grant
number: DBJ-0216310 (to N. Rawson).
NR 84
TC 17
Z9 17
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD JAN 20
PY 2009
VL 512
IS 3
BP 384
EP 398
DI 10.1002/cne.21899
PG 15
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 383XP
UT WOS:000261708000007
PM 19006182
ER
PT J
AU Hook-Barnard, IG
Hinton, DM
AF Hook-Barnard, India G.
Hinton, Deborah M.
TI The promoter spacer influences transcription initiation via sigma(70)
region 1.1 of Escherichia coli RNA polymerase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID OPEN COMPLEX-FORMATION; LAC UV5 PROMOTER; P-R PROMOTER;
CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; CLOSED
COMPLEXES; STRUCTURAL BASIS; DNA-SEQUENCE; A-TRACTS
AB Transcription initiation is a dynamic process in which RNA polymerase (RNAP) and promoter DNA act as partners, changing in response to one another, to produce a polymerase/promoter open complex (RPo) competent for transcription. In Escherichia coli RNAP, region 1.1, the N-terminal 100 residues of sigma(70), is thought to occupy the channel that will hold the DNA downstream of the transcription start site; thus, region 1.1 must move from this channel as RPo is formed. Previous work has also shown that region 1.1 can modulate RPo formation depending on the promoter. For some promoters region 1.1 stimulates the formation of open complexes; at the P-minor promoter, region 1.1 inhibits this formation. We demonstrate here that the AT-rich P-minor spacer sequence, rather than promoter recognition elements or downstream DNA, determines the effect of region 1.1 on promoter activity. Using a P-minor derivative that contains good sigma 70-dependent DNA elements, we find that the presence of a more GC-rich spacer or a spacer with the complement of the P-minor sequence results in a promoter that is no longer inhibited by region 1.1. Furthermore, the presence of the P-minor spacer, the GC-rich spacer, or the complement spacer results in different mobilities of promoter DNA during gel electrophoresis, suggesting that the spacer regions impart differing conformations or curvatures to the DNA. We speculate that the spacer can influence the trajectory or flexibility of DNA as it enters the RNAP channel and that region 1.1 acts as a "gatekeeper'' to monitor channel entry.
C1 [Hook-Barnard, India G.; Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hinton, DM (reprint author), NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
EM dhinton@helix.nih.gov
FU National Institutes of Health; National Institute of Diabetes and
Digestive and Kidney Diseases
FX We thank R. Bonocora, T. James, K. Baxter, L. Knipling, L. Shern, S.
Adhya, and R. Martin for helpful discussions. This work was supported by
the Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 59
TC 19
Z9 20
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 20
PY 2009
VL 106
IS 3
BP 737
EP 742
DI 10.1073/pnas.0808133106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399OR
UT WOS:000262809700014
PM 19139410
ER
PT J
AU Bukreyev, A
Marzi, A
Feldmann, F
Zhang, LQ
Yang, LJ
Ward, JM
Dorward, DW
Pickles, RJ
Murphy, BR
Feldmann, H
Collins, PL
AF Bukreyev, Alexander
Marzi, Andrea
Feldmann, Friederike
Zhang, Liqun
Yang, Lijuan
Ward, Jerrold M.
Dorward, David W.
Pickles, Raymond J.
Murphy, Brian R.
Feldmann, Heinz
Collins, Peter L.
TI Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein
as the sole surface protein is immunogenic and highly protective against
Ebola virus challenge
SO VIROLOGY
LA English
DT Article
DE Ebola virus; Vaccine; Antibody; Vector
ID POLARIZED EPITHELIAL-CELLS; VACCINIA VIRUS; RHESUS-MONKEYS; MARBURG
VIRUS; HEMAGGLUTININ-NEURAMINIDASE; NEUTRALIZING ANTIBODIES;
NUCLEOTIDE-SEQUENCE; ADENOVIRUS VECTORS; ANTI-AD5 IMMUNITY;
NONHUMAN-PRIMATES
AB We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/Delta F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/Delta F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/Delta F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV. Published by Elsevier Inc.
C1 [Bukreyev, Alexander; Yang, Lijuan; Ward, Jerrold M.; Murphy, Brian R.; Collins, Peter L.] NIAID, NIH, Bethesda, MD 20892 USA.
[Marzi, Andrea; Feldmann, Friederike; Feldmann, Heinz] Canadian Sci Ctr Human & Anim Hlth, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada.
[Zhang, Liqun; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA.
[Dorward, David W.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Bukreyev, A (reprint author), NIAID, NIH, Bldg 50,Room 6505,50 S Dr MSC 8007, Bethesda, MD 20892 USA.
EM abukreyev@nih.gov
FU NIAID Intramural Program; Public Health Agency of Canada; National
Institutes of Health (NIH) [NIH R01 HL77844-1]
FX This project was funded as a part of the NIAID Intramural Program,
Public Health Agency of Canada, and the National Institutes of Health
(NIH) grant NIH R01 HL77844-1.
NR 44
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U2 11
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 JAN 20
PY 2009
VL 383
IS 2
BP 348
EP 361
DI 10.1016/j.virol.2008.09.030
PG 14
WC Virology
SC Virology
GA 396QH
UT WOS:000262605700020
PM 19010509
ER
PT J
AU Lewis, GS
Cohen, TL
Seisler, AR
Kirby, KA
Sheehan, FT
Piazza, SJ
AF Lewis, Gregory S.
Cohen, Tamara L.
Seisler, Andrea R.
Kirby, Kevin A.
Sheehan, Frances T.
Piazza, Stephen J.
TI In vivo tests of an improved method for functional location of the
subtalar joint axis
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
ID DUAL EULER ANGLES; STANCE PHASE; TALOCALCANEAL JOINT; COORDINATE SYSTEM;
LOWER-EXTREMITY; MOTION; ANKLE; OPTIMIZATION; KINEMATICS; COMPLEX
C1 [Piazza, Stephen J.] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
[Cohen, Tamara L.] Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53201 USA.
[Lewis, Gregory S.; Piazza, Stephen J.] Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA.
[Seisler, Andrea R.; Sheehan, Frances T.] NIH, Bethesda, MD 20892 USA.
[Kirby, Kevin A.] Calif Sch Podiatr Med, Oakland, CA 94609 USA.
[Piazza, Stephen J.] Penn State Univ, Dept Orthopaed & Rehabil, Hershey, PA 17033 USA.
RP Piazza, SJ (reprint author), Penn State Univ, Dept Kinesiol, 29 Recreat Bldg, University Pk, PA 16802 USA.
EM sjp12@psu.edu
RI sheehan, frances/B-6962-2009; Piazza, Stephen/A-7731-2009
OI Piazza, Stephen/0000-0002-5026-7569
NR 42
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U1 1
U2 13
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 JAN 19
PY 2009
VL 42
IS 2
BP 146
EP 151
DI 10.1016/j.jbiomech.2008.10.010
PG 6
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 405BN
UT WOS:000263197200008
PM 19010472
ER
PT J
AU Veiseh, O
Gunn, JW
Kievit, FM
Sun, C
Fang, C
Lee, JSH
Zhang, MQ
AF Veiseh, Omid
Gunn, Jonathan W.
Kievit, Forrest M.
Sun, Conroy
Fang, Chen
Lee, Jerry S. H.
Zhang, Miqin
TI Inhibition of Tumor-Cell Invasion with Chlorotoxin-Bound
Superparamagnetic Nanoparticles
SO SMALL
LA English
DT Article
DE antitumor agents; biological materials; cells; imaging; peptides
ID PRIMARY BRAIN-TUMORS; MATRIX METALLOPROTEINASE-2; MOLECULAR-MECHANISMS;
CANCER-THERAPY; GLIOMA; MIGRATION; DIAGNOSIS
AB Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment are mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, a nanoparticle system that demonstrates an alternative approach to the treatment of cancers through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent, is presented. The nanoparticle comprises an iron oxide nanoparticle core conjugated with an amine-functionalized poly (ethylene glycol) silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. It is shown that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of similar to 98% compared to unbound CTX (similar to 45%). Significantly, the investigation from flow cytometry analysis, transmission electron microscopy, and fluorescent imaging reveals that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries, and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.
C1 [Veiseh, Omid; Gunn, Jonathan W.; Kievit, Forrest M.; Sun, Conroy; Fang, Chen; Zhang, Miqin] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Lee, Jerry S. H.] NCI, NIH, Bethesda, MD 20892 USA.
[Lee, Jerry S. H.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
RP Zhang, MQ (reprint author), Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
EM mzhang@u.washington.edu
RI Lee, Jerry/K-4553-2014; Zhang, Miqin/F-5537-2010; Lee,
Jerry/A-3189-2008; Veiseh, Omid/A-9972-2012; Sun, Conroy/B-5611-2013
OI Zhang, Miqin/0000-0001-8974-1494; Kievit, Forrest/0000-0002-9847-783X;
Lee, Jerry/0000-0003-1515-0952; Sun, Conroy/0000-0001-5193-6907
FU NIH [NO 5R01CA9408, NIBIB R01EB006043, NO 5R01CA112350, T32GM065098];
JWG; NCI; NSF IGERT; Ford Motor Company
FX This work is supported by NIH grants (NO 5R01CA9408, NIBIB R01EB006043,
and NO 5R01CA112350). We would like to acknowledge NIH training grant
(T32GM065098) for support of JWG, and NCI/NSF IGERT and Ford Motor
Company fellowships for support of OV and CS, respectively. We would
also like to acknowledge the lab assistance of Ms. Ni Mu and the use of
resources at the Diagnostic Imaging Sciences Center (DISC), and Keck
microscopy imaging facilities at the University of Washington.
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U2 53
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1613-6810
J9 SMALL
JI Small
PD JAN 19
PY 2009
VL 5
IS 2
BP 256
EP 264
DI 10.1002/smll.200800646
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 403NG
UT WOS:000263088700016
PM 19089837
ER
PT J
AU Looze, C
Yui, D
Leung, L
Ingham, M
Kaler, M
Yao, XL
Wu, WW
Shen, RF
Daniels, MP
Levine, SJ
AF Looze, Christopher
Yui, David
Leung, Lester
Ingham, Matthew
Kaler, Maryann
Yao, Xianglan
Wu, Wells W.
Shen, Rong-Fong
Daniels, Mathew P.
Levine, Stewart J.
TI Proteomic profiling of human plasma exosomes identifies PPAR gamma as an
exosome-associated protein
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Exosome; Plasma; Peroxisome proliferator-activated receptor-gamma;
Lipoprotein
ID VESICLES
AB Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-gamma (PPAR gamma), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatory cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPAR gamma as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors. Published by Elsevier Inc.
C1 [Looze, Christopher; Yui, David; Leung, Lester; Ingham, Matthew; Kaler, Maryann; Yao, Xianglan; Levine, Stewart J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Wells W.; Shen, Rong-Fong] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Daniels, Mathew P.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM levines@nblbi.nih.gov
FU Division of Intramural Research,; NHLBI; NIH
FX This work was funded by the Division of Intramural Research, NHLBI, NIH.
We are grateful to Patricia S. Connelly of the NHLBI Electron Microscopy
Core Facility for technical assistance.
NR 9
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PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 16
PY 2009
VL 378
IS 3
BP 433
EP 438
DI 10.1016/j.bbrc.2008.11.050
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 393AL
UT WOS:000262343200022
PM 19028452
ER
PT J
AU Kortum, RL
Samelson, LE
AF Kortum, Robert L.
Samelson, Lawrence E.
TI Priming the Pump: Adhesion Enhances T Cell Antigen Receptor-Induced
Signaling
SO IMMUNITY
LA English
DT Editorial Material
ID PROTEIN-KINASE; ACTIVATION; THRESHOLD
AB In this issue of Immunity, Conche et al. (2009) define an antigen-independent signaling pathway that is dependent on cyclic adenosine monophosphate and extracellular signal-regulated kinase and T cells for subsequent T cell antigen receptor signaling.
C1 [Kortum, Robert L.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
NR 10
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U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JAN 16
PY 2009
VL 30
IS 1
BP 3
EP 5
DI 10.1016/j.immuni.2008.12.007
PG 3
WC Immunology
SC Immunology
GA 398ZJ
UT WOS:000262769900002
PM 19144310
ER
PT J
AU Tolar, P
Hanna, J
Krueger, PD
Pierce, SK
AF Tolar, Pavel
Hanna, Joseph
Krueger, Peter D.
Pierce, Susan K.
TI The Constant Region of the Membrane Immunoglobulin Mediates B
Cell-Receptor Clustering and Signaling in Response to Membrane Antigens
SO IMMUNITY
LA English
DT Article
ID RESONANCE ENERGY-TRANSFER; LIVING CELLS; LYMPH-NODE; SUBCAPSULAR SINUS;
STRUCTURAL BASIS; BOUND ANTIGEN; T-CELLS; MICROCLUSTERS; ACTIVATION;
LIGAND
AB B cells are activated in vivo after the B cell receptors (BCRs) bind to antigens captured on the surfaces of antigen-presenting cells. Antigen binding results in BCR microclustering and signaling; however, the molecular nature of the signaling-active BCR clusters is not well understood. Using single-molecule imaging techniques, we provide evidence that within microclusters, the binding of monovalent membrane antigens results in the assembly of immobile signaling-active BCR oligomers. The oligomerization depends on interactions between the membrane-proximal C mu 4 domains of the membrane immunoglobulin that are both necessary and sufficient for assembly. Antigen-bound BCRs that lacked the C mu 4 domain failed to cluster and signal, and conversely, C mu 4 domains alone clustered spontaneously and activated B cells. These results support a unique mechanism for the initiation of BCR signaling in which antigen binding induces a conformational change in the Fc portion of the BCR, revealing an interface that promotes BCR clustering.
C1 [Tolar, Pavel; Hanna, Joseph; Krueger, Peter D.; Pierce, Susan K.] NIAID, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA.
RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA.
EM spierce@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank M. Davis and J. Huppa for advice on bilayer preparation, T.
Meckel for advice on single-molecule data analysis, C.-Y. Huang for
advice on statistical analysis, and J. Brzostowski for help with imaging
and comments on the manuscript. This work has been supported by the
Intramural Research program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JAN 16
PY 2009
VL 30
IS 1
BP 44
EP 55
DI 10.1016/j.immuni.2008.11.007
PG 12
WC Immunology
SC Immunology
GA 398ZJ
UT WOS:000262769900009
PM 19135393
ER
PT J
AU Wei, G
Wei, L
Zhu, JF
Zang, CZ
Hu-Li, J
Yao, ZJ
Cui, KR
Kanno, Y
Roh, TY
Watford, WT
Schones, DE
Peng, WQ
Sun, HW
Paul, WE
O'Shea, JJ
Zhao, KJ
AF Wei, Gang
Wei, Lai
Zhu, Jinfang
Zang, Chongzhi
Hu-Li, Jane
Yao, Zhengju
Cui, Kairong
Kanno, Yuka
Roh, Tae-Young
Watford, Wendy T.
Schones, Dustin E.
Peng, Weiqun
Sun, Hong-wei
Paul, William E.
O'Shea, John J.
Zhao, Keji
TI Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and
Plasticity in Lineage Fate Determination of Differentiating CD4(+) T
Cells
SO IMMUNITY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HUMAN GENOME; GENE-EXPRESSION; TGF-BETA;
TRANSCRIPTION FACTORS; FOXP3 EXPRESSION; HELPER TYPE-1; T(H)17 CELLS;
TH17 CELLS; TH2 CELLS
AB Multipotential naive CD4(+) T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4(+) T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naive, Th1, Th2, Th17, iTreg, and natural Treg (nTreg) cells. We found that although modifications of signature-cytokine genes (Ifng, II4, and II17) partially conform to the expectation of lineage commitment, genes encoding transcription factors like Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and interferon-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4(+) T helper cell differentiation.
C1 [Wei, Lai; Yao, Zhengju; Kanno, Yuka; Watford, Wendy T.; O'Shea, John J.] NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Wei, Gang; Cui, Kairong; Roh, Tae-Young; Schones, Dustin E.; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Sun, Hong-wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
[Zang, Chongzhi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
RP O'Shea, JJ (reprint author), NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
EM osheajo@mail.nih.gov; zhaok@nhlbi.nih.gov
RI Wei, Gang/A-3291-2011; Zhu, Jinfang/B-7574-2012; Zang,
Chongzhi/D-1445-2011; Kanno, Yuka/B-5802-2013; Wei, Lai/D-1088-2014;
OI Kanno, Yuka/0000-0001-5668-9319
FU National Institute of Allergy and Infectious Diseases (NIAID); NHLBI;
NIAMS
FX We thank W. Leonard for critical reading of the manuscript and J. Simone
for technical help with cell sorting. The gene-expression analysis with
the Affymetrix microarrays was performed by the Gene Expression Gore
Facilities of National Heart, Lung, and Blood Institute (NHLBI) and the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS). This research was supported by the Intramural Research Programs
of the National Institute of Allergy and Infectious Diseases (NIAID),
NHLBI, and NIAMS.
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U2 32
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JAN 16
PY 2009
VL 30
IS 1
BP 155
EP 167
DI 10.1016/j.immuni.2008.12.009
PG 13
WC Immunology
SC Immunology
GA 398ZJ
UT WOS:000262769900018
PM 19144320
ER
PT J
AU Volodin, AA
Bocharova, TN
Smirnova, EA
Camerini-Otero, RD
AF Volodin, Alexander A.
Bocharova, Tatiana N.
Smirnova, Elena A.
Camerini-Otero, R. Daniel
TI Reversibility, Equilibration, and Fidelity of Strand Exchange Reaction
between Short Oligonucleotides Promoted by RecA Protein from Escherichia
coli and Human Rad51 and Dmc1 Proteins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HOMOLOGOUS GENETIC-RECOMBINATION; ATP HYDROLYSIS; DUPLEX DNA;
HETERODUPLEX PRODUCT; HOP2-MND1 COMPLEX; SYNAPTIC COMPLEX;
ENERGY-TRANSFER; BINDING; FILAMENT; RECOGNITION
AB We demonstrate the reversibility of RecA-promoted strand exchange reaction between short oligonucleotides in the presence of adenosine 5'-O-(thiotriphosphate). The reverse reaction proceeds without the dissociation of RecA from DNA. The reaction reaches equilibrium and its yield depends on the homology between the reaction substrates. We estimate the tolerance of the RecA-promoted strand exchange to individual base substitutions for a comprehensive set of possible base combinations in a selected position along oligonucleotide substrates for strand exchange and find, in agreement with previously reported estimations, that this tolerance is higher than in the case of free DNA. It is demonstrated that the short oligonucleotide-based approach can be applied to the human recombinases Rad51 and Dmc1 when strand exchange is performed in the presence of calcium ions and ATP. Remarkably, despite the commonly held belief that the eukaryotic recombinases have an inherently lower strand exchange activity, in our system their efficiencies in strand exchange are comparable with that of RecA. Under our experimental conditions, the human recombinases exhibit a significantly higher tolerance to interruptions of homology due to point base substitutions than RecA. Finding conditions where a chemical reaction is reversible and reaches equilibrium is critically important for its thermodynamically correct description. We believe that the experimental system described here will substantially facilitate further studies on different aspects of the mechanisms of homologous recombination.
C1 [Volodin, Alexander A.; Bocharova, Tatiana N.; Smirnova, Elena A.] Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia.
[Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Camerini-Otero, RD (reprint author), Bldg 5,Rm 205A,5 Mem Dr,MSC0538, Bethesda, MD 20892 USA.
EM camerini@ncifcrf.gov
RI Volodin, Alexander/B-9656-2012
FU National Institutes of Health
FX This work was authored, in whole or in part, by National Institutes of
Health staff. The costs of publication of this article were defrayed in
part by the payment of page charges. This article must therefore be
hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
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U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 16
PY 2009
VL 284
IS 3
BP 1495
EP 1504
DI 10.1074/jbc.M800612200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 392VK
UT WOS:000262330100017
PM 19004837
ER
PT J
AU Nakayama, M
Hisatsune, J
Yamasaki, E
Isomoto, H
Kurazono, H
Hatakeyama, M
Azuma, T
Yamaoka, Y
Yahiro, K
Moss, J
Hirayama, T
AF Nakayama, Masaaki
Hisatsune, Junzo
Yamasaki, Eiki
Isomoto, Hajime
Kurazono, Hisao
Hatakeyama, Masanori
Azuma, Takeshi
Yamaoka, Yoshio
Yahiro, Kinnosuke
Moss, Joel
Hirayama, Toshiya
TI Helicobacter pylori VacA-induced Inhibition of GSK3 through the PI3K/Akt
Signaling Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; GASTRIC EPITHELIAL-CELLS; BETA-CATENIN SIGNAL; AZ-521 CELLS;
VACUOLATING TOXIN; WNT PATHWAY; ACTIVATION; PROTEIN; INDUCTION;
CYTOTOXIN
AB Helicobacter pylori VacA toxin contributes to the pathogenesis and severity of gastric injury. We found that incubation of AZ-521 cells with VacA resulted in phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3 beta (GSK3 beta) through a PI3K-dependent pathway. Following phosphorylation and inhibition of GSK3 beta,beta-catenin was released from a GSK3 beta/beta-catenin complex, with subsequent nuclear translocation. Methyl-beta-cyclodextrin (MCD) and phosphatidylinositol-specific phospholipase C (PIPLC), but not 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and bafilomycin A1, inhibited VacA-induced phosphorylation of Akt, indicating that it does not require VacA internalization and is independent of vacuolation. VacA treatment of AZ-521 cells transfected with TOPtkLuciferase reporter plasmid or control FOPtkLucifease reporter plasmid resulted in activation of TOPtkLuciferase, but not FOPtkLucifease. In addition, VacA transactivated the beta-catenin-dependent cyclin D1 promoter in a luciferase reporter assay. Infection of AZ-521 cells by a vacA mutant strain of H. pylori failed to induce phosphorylation of Akt and GSK3 beta, or release of beta-catenin from a GSK3 beta/beta-catenin complex. Taken together, these results support the conclusion that VacA activates the PI3K/Akt signaling pathway, resulting in phosphorylation and inhibition of GSK3 beta, and subsequent translocation of beta-catenin to the nucleus, consistent with effects of VacA on beta-catenin-regulated transcriptional activity. These data introduce the possibility that Wnt-dependent signaling might play a role in the pathogenesis of H. pylori infection, including the development of gastric cancer.
C1 [Nakayama, Masaaki; Hisatsune, Junzo; Hirayama, Toshiya] Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan.
[Yamasaki, Eiki; Kurazono, Hisao] Obihiro Univ Agr & Vet Med, Dept Appl Vet Med & Publ Hlth, Obihiro, Hokkaido 0808555, Japan.
[Isomoto, Hajime] Nagasaki Univ, Dept Endoscopy, Sch Med, Nagasaki 8528523, Japan.
[Hatakeyama, Masanori] Hokkaido Univ, Div Mol Oncol, Inst Med Genet, Sapporo, Hokkaido 0600815, Japan.
[Azuma, Takeshi] Kobe Univ, Sch Med, Dept Gastroenterol, Kobe, Hyogo 6500017, Japan.
[Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA.
[Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA.
[Yahiro, Kinnosuke; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Hirayama, T (reprint author), Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan.
EM hirayama@net.nagasaki-u.ac.jp
FU Intramural Research Program of the NHLBI; National Institutes of Health;
Ministry of Education, Culture, Sports, Science and Technology of Japan
FX This work was supported, in whole or in part, by the Intramural Research
Program of the NHLBI, National Institutes of Health (to J. M.). This
work was also supported by Grants-in-aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology of
Japan. The costs of publication of this article were defrayed in part by
the payment of page charges. This article must therefore be hereby
marked "advertisement" in accordance with 18 U. S. C. Section 1734
solely to indicate this fact.
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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 JAN 16
PY 2009
VL 284
IS 3
BP 1612
EP 1619
DI 10.1074/jbc.M806981200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 392VK
UT WOS:000262330100029
PM 18996844
ER
PT J
AU Jian, XY
Brown, P
Schuck, P
Gruschus, JM
Balbo, A
Hinshaw, JE
Randazzo, PA
AF Jian, Xiaoying
Brown, Patrick
Schuck, Peter
Gruschus, James M.
Balbo, Andrea
Hinshaw, Jenny E.
Randazzo, Paul A.
TI Autoinhibition of Arf GTPase-activating Protein Activity by the BAR
Domain in ASAP1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHOLIPASE A2 ACTIVITY; MEMBRANE CURVATURE; RECYCLING ENDOSOME; ACTIN
CYTOSKELETON; PH DOMAINS; GAPS; BINDING; FAMILY; ULTRACENTRIFUGATION;
RECOGNITION
AB ASAP1 is an Arf GTPase-activating protein (GAP) that functions on membrane surfaces to catalyze the hydrolysis of GTP bound to Arf. ASAP1 contains a tandem of BAR, pleckstrin homology (PH), and Arf GAP domains and contributes to the formation of invadopodia and podosomes. The PH domain interacts with the catalytic domain influencing both the catalytic and Michaelis constants. Tandem BAR-PH domains have been found to fold into a functional unit. The results of sedimentation velocity studies were consistent with predictions from homology models in which the BAR and PH domains of ASAP1 fold together. We set out to test the hypothesis that the BAR domain of ASAP1 affects GAP activity by interacting with the PH and/or Arf GAP domains. Recombinant proteins composed of the BAR, PH, Arf GAP, and Ankyrin repeat domains (called BAR-PZA) and the PH, Arf GAP, and Ankyrin repeat domains (PZA) were compared. Catalytic power for the two proteins was determined using large unilamellar vesicles as a reaction surface. The catalytic power of PZA was greater than that of BAR-PZA. The effect of the BAR domain was dependent on the N-terminal loop of the BAR domain and was not the consequence of differential membrane association or changes in large unilamellar vesicle curvature. The K(m) for BAR-PZA was greater and the k(cat) was smaller than for PZA determined by saturation kinetics. Analysis of single turnover kinetics revealed a transition state intermediate that was affected by the BAR domain. We conclude that BAR domains can affect enzymatic activity through intraprotein interactions.
C1 [Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Brown, Patrick; Schuck, Peter; Balbo, Andrea] NIDDK, Sect Dynam Macromol Assembly, NIH, Bethesda, MD 20892 USA.
[Gruschus, James M.] NIDDK, NHLBI, NIH, Bethesda, MD 20892 USA.
[Hinshaw, Jenny E.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Rm 2042, Bethesda, MD 20892 USA.
EM randazzo@helix.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU NCI; NIBIB; National Institutes of Health; Department of Health and
Human Services
FX This work was supported, in whole or in part, by the intramural program
at NCI and by the NIBIB, National Institutes of Health, Department of
Health and Human Services. The costs of publication of this article were
defrayed in part by the payment of page charges. This article must
therefore be hereby marked "advertisement" in accordance with 18 U. S.
C. Section 1734 solely to indicate this fact.
NR 42
TC 35
Z9 35
U1 1
U2 15
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 JAN 16
PY 2009
VL 284
IS 3
BP 1652
EP 1663
DI 10.1074/jbc.M804218200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 392VK
UT WOS:000262330100034
PM 19017632
ER
PT J
AU Lin, HY
Fridy, PC
Ribeiro, AA
Choi, JH
Barma, DK
Vogel, G
Falck, JR
Shears, SB
York, JD
Mayr, GW
AF Lin, Hongying
Fridy, Peter C.
Ribeiro, Anthony A.
Choi, Jae H.
Barma, Deb K.
Vogel, Guenter
Falck, J. R.
Shears, Stephen B.
York, John D.
Mayr, Georg W.
TI Structural Analysis and Detection of Biological Inositol Pyrophosphates
Reveal That the Family of VIP/Diphosphoinositol Pentakisphosphate
Kinases Are 1/3-Kinases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE; HEXAKISPHOSPHATE
KINASE; DICTYOSTELIUM; TETRAKISPHOSPHATE; PHOSPHATES; IDENTIFICATION;
PURIFICATION; METABOLISM; CELLS; POLYSPHONDYLIUM
AB We have characterized the positional specificity of the mammalian and yeast VIP/diphosphoinositol pentakisphosphate kinase (PPIP5K) family of inositol phosphate kinases. We deployed a microscale metal dye detection protocol coupled to a high performance liquid chromatography system that was calibrated with synthetic and biologically synthesized standards of inositol pyrophosphates. In addition, we have directly analyzed the structures of biological inositol pyrophosphates using two-dimensional (1)H-(1)H and (1)H-(31)P nuclear magnetic resonance spectroscopy. Using these tools, we have determined that the mammalian and yeast VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo. For example, the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate. The latter compound has not previously been identified in any organism. We have also unequivocally determined that 1/3,5-(PP)(2)-IP(4) is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals, through a collaboration between the inositol hexakisphosphate kinase and VIP/PPIP5K enzymes. These data uncover phylogenetic variability within the crown taxa in the structures of inositol pyrophosphates. For example, in the Dictyostelids, the major bis-diphosphoinositol tetrakisphosphate is 5,6-(PP)(2)-IP(4) (Laussmann, T., Eujen, R., Weisshuhn, C. M., Thiel, U., Falck, J. R., and Vogel, G. (1996) Biochem. J. 315, 715-725). Our study brings us closer to the goal of understanding the structure/function relationships that control specificity in the synthesis and biological actions of inositol pyrophosphates.
C1 [Lin, Hongying; Mayr, Georg W.] Univ Klinikum Hamburg Eppendorf, Inst Biochem & Mol Biol Zellulare Signaltransdukt, D-20246 Hamburg, Germany.
[Fridy, Peter C.; York, John D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Ribeiro, Anthony A.] Duke Univ, Med Ctr, NMR Ctr, Durham, NC 27710 USA.
[Ribeiro, Anthony A.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Ribeiro, Anthony A.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Choi, Jae H.; Shears, Stephen B.] NIEHS, Inositide Signaling Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Barma, Deb K.; Falck, J. R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Vogel, Guenter] Berg Univ Wuppertal, Fachbereich Math & Nat Wissensch Biochem, D-42097 Wuppertal, Germany.
RP Mayr, GW (reprint author), Univ Klinikum Hamburg Eppendorf, Inst Biochem & Mol Biol Zellulare Signaltransdukt, Martinistr 52, D-20246 Hamburg, Germany.
EM mayr@uke.uni-hamburg.de
OI Fridy, Peter/0000-0002-8208-9154; Falck, John/0000-0002-9219-7845
FU National Institutes of Health (NIH) Intramural Research Program of the
NIEHS; NIH [R01 HL-55672, R01 A1057588]; Howard Hughes Medical
Institute; Deutsche Forschungsgemeinschaft [MA 989/2-3]; National
Science Foundation; NIH; North Carolina Biotechnology Center; Duke
University; [NCI P30CA- 14236]
FX This work was supported, in whole or in part, by the National Institutes
of Health (NIH) Intramural Research Program of the NIEHS ( to S. B. S.)
and NIH Grants R01 HL-55672 ( to J. D. Y.), R01 A1057588 ( to A. A. R.),
and NCI P30CA- 14236 ( to A. A. R.). This research was also supported by
the Howard Hughes Medical Institute ( to J. D. Y.) and Deutsche
Forschungsgemeinschaft Grant MA 989/2-3 ( to G. W. M.). Instrumentation
in the Duke NMR Center is funded by the National Science Foundation, the
NIH, the North Carolina Biotechnology Center, and Duke University. The
costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 38
TC 62
Z9 64
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 JAN 16
PY 2009
VL 284
IS 3
BP 1863
EP 1872
DI 10.1074/jbc.M805686200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 392VK
UT WOS:000262330100057
PM 18981179
ER
PT J
AU Lu, WB
Ma, H
Sheng, ZH
Mochida, S
AF Lu, Wenbo
Ma, Huan
Sheng, Zu-Hang
Mochida, Sumiko
TI Dynamin and Activity Regulate Synaptic Vesicle Recycling in Sympathetic
Neurons
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; FROG NEUROMUSCULAR JUNCTION; HIPPOCAMPAL
SYNAPSES; TRANSMITTER RELEASE; DROSOPHILA MUTANT; GANGLION NEURONS;
NERVE-TERMINALS; MEMBRANE; AMPHIPHYSIN; CHANNELS
AB Neurotransmission in central neuronal synapses is supported by the recycling of synaptic vesicles via endocytosis at different time scales during and after transmitter release. Here, we examine the kinetics and molecular determinants of different modes of synaptic vesicle recycling at a peripheral neuronal synapse formed between superior cervical ganglion neurons in culture, via acute disruption of endocytosis with Dynasore, an inhibitor of dynamin activation, or a dynamin peptide (P4) that perturbs linkage of dynamin to clathrin coats through amphiphysin. When paired action potentials are generated to produce excitatory postsynaptic potential responses, the second response was reduced after application of Dynasore but not P4. In addition, graded reduction in synaptic transmission during a train of action potentials was accelerated by Dynasore but enhanced by P4. After full depletion of releasable vesicles, P4 delayed the recovery of synaptic transmission while Dynasore limited recovery to 10%. In control neurons, synaptic transmission is stable for more than 1 h under low frequency presynaptic stimulation (0.2 Hz), but was reduced gradually by P4 and rapidly but incompletely blocked by Dynasore at a much lower stimulation frequency. These results suggest two essential modes of dynamin-mediated synaptic vesicle recycling, one activity-dependent and the other activity-independent. Our findings extend the current understanding of synaptic vesicle recycling to sympathetic nerve terminals and provide evidence for a physiological and molecular heterogeneity in endocytosis, a key cellular process for efficient replenishment of the vesicle pool, and thus for synaptic plasticity.
C1 [Mochida, Sumiko] Tokyo Med Univ, Dept Physiol, Shinjuku Ku, Tokyo 1608402, Japan.
[Lu, Wenbo; Ma, Huan; Mochida, Sumiko] Shanghai Jiao Tong Univ, Dept Neurobiol, Sch Med, Shanghai 200025, Peoples R China.
[Sheng, Zu-Hang] NINDS, Synapt Funct Sect, NIH, Bethesda, MD 20892 USA.
RP Mochida, S (reprint author), Tokyo Med Univ, Dept Physiol, Shinjuku Ku, 1-1 Shinjuku 6 Chome, Tokyo 1608402, Japan.
EM mochida@tokyo-med.ac.jp
RI Ma, Huan/A-1379-2012
NR 46
TC 19
Z9 21
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 JAN 16
PY 2009
VL 284
IS 3
BP 1930
EP 1937
DI 10.1074/jbc.M803691200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 392VK
UT WOS:000262330100063
PM 19010787
ER
PT J
AU Maul, RW
Gearhart, PJ
AF Maul, Robert W.
Gearhart, Patricia J.
TI Women, autoimmunity, and cancer: a dangerous liaison between estrogen
and activation-induced deaminase?
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; B-CELLS; EXPRESSION; AID; MICRORNA-155;
NUCLEUS
AB Why women are more susceptible to autoimmune diseases is not completely clear, but new data suggest that the hormone estrogen may play an important role. A new study now shows that estrogen activates the expression of activation-induced deaminase (AID), a protein that drives antibody diversification by deaminating cytosine in DNA to uracil. If estrogen increases the level of AID, increased mutations could transform benign antibodies into anti-self pariahs. AID might also contribute to cancer-particularly in breast tissue, which is highly responsive to estrogen-by introducing mutations and strand breaks into the genome.
C1 [Maul, Robert W.; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@grc.nia.nih.gov
OI Maul, Robert/0000-0002-6958-8514
NR 19
TC 10
Z9 11
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JAN 16
PY 2009
VL 206
IS 1
BP 11
EP 13
DI 10.1084/jem.20080086
PG 3
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VK
UT WOS:000266008300003
PM 19139165
ER
PT J
AU Takatori, H
Kanno, Y
Watford, WT
Tato, CM
Weiss, G
Ivanov, II
Littman, DR
O'Shea, JJ
AF Takatori, Hiroaki
Kanno, Yuka
Watford, Wendy T.
Tato, Cristina M.
Weiss, Greta
Ivanov, Ivaylo I.
Littman, Dan R.
O'Shea, John J.
TI Lymphoid tissue inducer-like cells are an innate source of IL-17 and
IL-22
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID T-HELPER-CELLS; AUTOIMMUNE INFLAMMATION; TH17 CELLS; CD4(+)CD3(-) CELLS;
DIFFERENTIATION; EXPRESSION; CYTOKINE; RECEPTOR; DRIVES; INTERLEUKIN-12
AB The interleukin (IL) 17 family of cytokines has emerged to be critical for host defense as well as the pathogenesis of autoimmune and autoinflammatory disorders, and serves to link adaptive and innate responses. Recent studies have identified a new subset of T cells that selectively produce IL-17 (Th17 cells; Bettelli, E., T. Korn, and V. K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652-657; Kolls, J.K., and A. Linden. 2004. Immunity. 21: 467 476), but the regulation of IL-17 production by innate immune cells is less well understood. We report that in vitro stimulation with IL-23 induced IL-17 production by recombination activating gene (Rag) 2(-/-) splenocytes but not Rag2(-/-) common gamma chain(-/-) splenocytes. We found that a major source of IL-17 was CD4(+)CD3(-)NK1.1(-)CD11b(-)Gr1(-)CD 11c(-)B220(-) cells, a phenotype that corresponds to lymphoid tissue inducer-like cells (LTi-like cells), which constitutively expressed the IL-23 receptor, aryl hydrocarbon receptor, and CCR6. In vivo challenge with the yeast cell wall product zymosan rapidly induced IL-17 production in these cells. Genetic deletion of signal transducer and activator of transcription 3 reduced but did not abrogate IL-17 production in LTi-like cells. Thus, it appears that splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might contribute to dynamic organization of secondary lymphoid organ structure or host defense.
C1 [Takatori, Hiroaki; Kanno, Yuka; Watford, Wendy T.; Tato, Cristina M.; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Weiss, Greta] Univ Penn, NIH, Grad Program, Bethesda, MD 20892 USA.
[Ivanov, Ivaylo I.; Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, Skirball Inst Biomol Med, New York, NY 10016 USA.
RP Takatori, H (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
EM takatorih@mail.nih.gov
RI Kanno, Yuka/B-5802-2013;
OI Kanno, Yuka/0000-0001-5668-9319
FU Intramural NIH HHS
NR 30
TC 392
Z9 397
U1 1
U2 27
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JAN 16
PY 2009
VL 206
IS 1
BP 35
EP 41
DI 10.1084/jem.20072713
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VK
UT WOS:000266008300006
PM 19114665
ER
PT J
AU Dienz, O
Eaton, SM
Bond, JP
Neveu, W
Moquin, D
Noubade, R
Briso, EM
Charland, C
Leonard, WJ
Ciliberto, G
Teuscher, C
Haynes, L
Rincon, M
AF Dienz, Oliver
Eaton, Sheri M.
Bond, Jeffrey P.
Neveu, Wendy
Moquin, David
Noubade, Rajkumar
Briso, Eva M.
Charland, Colette
Leonard, Warren J.
Ciliberto, Gennaro
Teuscher, Cory
Haynes, Laura
Rincon, Mercedes
TI The induction of antibody production by IL-6 is indirectly mediated by
IL-21 produced by CD4(+) T cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID FOLLICULAR-HELPER-CELLS; TRANSGENIC MICE; B-CELLS; TH1 CELLS;
DIFFERENTIATION; INTERLEUKIN-6; GENERATION; CYTOKINE; RECEPTOR; ANTIGEN
AB Interleukin (IL) 6 is a proinflammtory cytokine produced by antigen-presenting cells and nonhematopoietic cells in response to external stimuli. It was initially identified as a B cell growth factor and inducer of plasma cell differentiation in vitro and plays an important role in antibody production and class switching in vivo. However, it is not clear whether IL-6 directly affects B cells or acts through other mechanisms. We show that IL-6 is sufficient and necessary to induce IL-21 production by naive and memory CD4(+) T cells upon T cell receptor stimulation. IL-21 production by CD4(+) T cells is required for IL-6 to promote B cell antibody production in vitro. Moreover, administration of IL-6 with inactive influenza virus enhances virus-specific antibody production, and importantly, this effect is dependent on IL-21. Thus, IL-6 promotes antibody production by promoting the B cell helper capabilities of CD4(+) T cells through increased IL-21 production. IL-6 could therefore be a potential coadjuvant to enhance humoral immunity.
C1 [Dienz, Oliver; Neveu, Wendy; Moquin, David; Noubade, Rajkumar; Briso, Eva M.; Charland, Colette; Teuscher, Cory; Rincon, Mercedes] Univ Vermont, Dept Med, Immunobiol Program, Burlington, VT 05405 USA.
[Dienz, Oliver; Neveu, Wendy; Moquin, David; Noubade, Rajkumar; Briso, Eva M.; Charland, Colette; Teuscher, Cory; Rincon, Mercedes] Univ Vermont, Dept Microbiol & Mol Genet Bioinformat, Burlington, VT 05405 USA.
[Eaton, Sheri M.; Haynes, Laura] Trudeau Inst Inc, Saranac Lake, NY 12983 USA.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Ciliberto, Gennaro] Ist Ric Biol Mol P Angeletti, I-00040 Rome, Italy.
RP Rincon, M (reprint author), Univ Vermont, Dept Med, Immunobiol Program, Burlington, VT 05405 USA.
EM mrincon@uvm.edu
OI Ciliberto, Gennaro/0000-0003-2851-8605
FU NCRR NIH HHS [P20 RR016462, P20 RR021905, P20 RR16462]; NIAID NIH HHS
[P01AI045666, P01 AI045666]
NR 42
TC 149
Z9 159
U1 1
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JAN 16
PY 2009
VL 206
IS 1
BP 69
EP 78
DI 10.1084/jem.20081571
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VK
UT WOS:000266008300010
PM 19139170
ER
PT J
AU Acker, MG
Shin, BS
Nanda, JS
Saini, AK
Dever, TE
Lorsch, JR
AF Acker, Michael G.
Shin, Byung-Sik
Nanda, Jagpreet S.
Saini, Adesh K.
Dever, Thomas E.
Lorsch, Jon R.
TI Kinetic Analysis of Late Steps of Eukaryotic Translation Initiation
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE eukaryotic translation initiation; protein synthesis; eIF1A; eIF5B;
subunit joining
ID START CODON SELECTION; 40S RIBOSOMAL-SUBUNIT; PROTEIN-SYNTHESIS;
IN-VIVO; SACCHAROMYCES-CEREVISIAE; PREINITIATION COMPLEX; RABBIT
RETICULOCYTES; LIGHT-SCATTERING; SITE SELECTION; GTP HYDROLYSIS
AB Little is known about the molecular mechanics of the late events of translation initiation in eukaryotes. We present a kinetic dissection of the transition from a preinitiation complex after start codon recognition to the final 80S initiation complex. The resulting framework reveals that eukaryotic initiation factor (eIF)5B actually accelerates the rate of ribosomal subunit Joining, and this acceleration is influenced by the conformation of the GTPase active site of the factor mediated by the bound nucleotide. eIF1A accelerates joining through its C-terminal interaction with eIF5B, and eIF1A release from the initiating ribosome, which occurs only after subunit joining, is accelerated by GTP hydrolysis by eIF5B. Following subunit joining, GTP hydrolysis by eIF5B alters the conformation of the final initiation complex and clears a path to promote rapid release of eIF1A. Our data, coupled with previous work, indicate that eIF1A is present on the ribosome throughout the entire initiation process and plays key roles at every stage. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Acker, Michael G.; Nanda, Jagpreet S.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Shin, Byung-Sik; Saini, Adesh K.; Dever, Thomas E.] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM jlorsch@jhmi.edu
RI Nanda, Jagpreet/F-9833-2011;
OI Dever, Thomas/0000-0001-7120-9678; Lorsch, Jon/0000-0002-4521-4999
FU National Institutes of Health [GM62128]; American Cancer Society
[RSG-03-156-01]; National Institutes of Health; National Institute of
Child Health and Human Development
FX We thank members of our labs and Alan Hinnebusch for comments on the
manuscript. Work on eIF1A was funded by National Institutes of Health
grant GM62128 to J.R.L., and work on eIF5B was funded by American Cancer
Society grant RSG-03-156-01 to J.R.L. This work was also supported by
the Intramural Research Program of the National Institutes of Health,
National Institute of Child Health and Human Development (to T.E.D.).
NR 56
TC 35
Z9 36
U1 0
U2 0
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 JAN 16
PY 2009
VL 385
IS 2
BP 491
EP 506
DI 10.1016/j.jmb.2008.10.029
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 401CV
UT WOS:000262916900013
PM 18976658
ER
PT J
AU Plaza, A
Bifulco, G
Keffer, JL
Lloyd, JR
Baker, HL
Bewley, CA
AF Plaza, Alberto
Bifulco, Giuseppe
Keffer, Jessica L.
Lloyd, John R.
Baker, Heather L.
Bewley, Carole A.
TI Celebesides A-C and Theopapuamides B-D, Depsipeptides from an Indonesian
Sponge That Inhibit HIV-1 Entry
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID BIOACTIVE MARINE METABOLITES; TETRAMIC ACID GLYCOSIDES; HETERONUCLEAR
COUPLING-CONSTANTS; CONSTITUENT AMINO-ACIDS; THEONELLA-SWINHOEI;
SILIQUARIASPONGIA-JAPONICA; RELATIVE CONFIGURATION;
ABSOLUTE-CONFIGURATION; ORGANIC-COMPOUNDS; PRACTICAL ASPECTS
AB Six new depsipeptides belonging to two different structural classes, termed celebesides A-C and theopapuamides B-D, have been isolated from the marine sponge Siliquariaspongia mirabilis. Their structures were determined using extensive 2D NMR and ESI-MS/MS techniques. Celebesides are unusual cyclic depsipeptides that comprise a polyketide moiety and five amino acid residues, including an uncommon 3-carbamoyl threonine, and a phosphoserine residue in celebesides A and B. Theopapuamides B-D are undecapeptides with an N-terminal fatty acid moiety containing two previously unreported amino acids, 3-acetamido-2-aminopropanoic acid and 4-amino-2,3-dihydroxy-5-methylhexanoic acid. The relative configuration of the polyketide moiety in celebesides was resolved by J-based analysis and quantum mechanical calculations, the results of which were self-consistent. Celebeside A neutralized HIV-1 in a single-round infectivity assay with an IC(50) value of 1.9 +/- 0.4 mu g/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 mu g/mL. Theopapuamides A-C showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC(50) values between 2.1 and 4.0 mu g/mL and exhibited strong antifungal activity against wildtype and amphotericin B-resistant strains of Candida albicans at loads of 1-5 mu g/disk.
C1 [Plaza, Alberto; Keffer, Jessica L.; Lloyd, John R.; Baker, Heather L.; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Bifulco, Giuseppe] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Salerno, Italy.
RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
RI Bifulco, Giuseppe/A-5413-2011;
OI Bifulco, Giuseppe/0000-0002-1788-5170; Keffer,
Jessica/0000-0002-0302-3588
FU NIH Intramural Research Program; Intramural AIDS Targeted Antiviral
Program; Office of the Director, NIH
FX We thank the Coral Reef Research Foundation, D. Newman, and the country
of Indonesia for making possible sample acquisition; M. Kelly and the
National Cancer Institute for sponge taxonomy; L. Bell, CRRF, for
helpful discussions; and the AIDS Research and Reference Reagent
Program, Division of AIDS, NIAID, NIH, for reagents and cell lines used
in the HIV-1 neutralization assays. This work was supported in part by
the NIH Intramural Research Program (NLDDK) and the Intramural AIDS
Targeted Antiviral Program, Office of the Director, NIH (C.A.B.).
NR 39
TC 47
Z9 49
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD JAN 16
PY 2009
VL 74
IS 2
BP 504
EP 512
DI 10.1021/jo802232u
PG 9
WC Chemistry, Organic
SC Chemistry
GA 392YS
UT WOS:000262338700003
PM 19072692
ER
PT J
AU Hayakawa, J
Washington, K
Uchida, N
Phang, O
Kang, EM
Hsieh, MM
Tisdale, JF
AF Hayakawa, Jun
Washington, Kareem
Uchida, Naoya
Phang, Oswald
Kang, Elizabeth M.
Hsieh, Matthew M.
Tisdale, John F.
TI Long-Term Vector Integration Site Analysis Following Retroviral Mediated
Gene Transfer to Hematopoietic Stem Cells for the Treatment of HIV
Infection
SO PLOS ONE
LA English
DT Article
AB We previously reported the efficacy of nonmyeloablative allogeneic transplantation in 2 HIV positive recipients, one of whom received retrovirus transduced hematopoietic stem cells to confer resistance to HIV. Here we report an assessment of retroviral integration sites (RISs) recovered out to 3 years post-transplantation. We identified 213 unique RISs from the patient's peripheral blood samples by linear amplification-mediated PCR (LAM-PCR). While vector integration patterns were similar to that previously reported, only 3.76% of RISs were common among early (up to 3 months) and late samples (beyond 1 year). Additionally, common integration sites were enriched among late samples (14.9% vs. 36.8%, respectively). Three RISs were found near or within known oncogenes, but 2 were limited to early timepoints. Interestingly, an integration site near the MDS1 gene was detected in long-term follow-up samples; however, the overall contribution of MDS1 integrated clone remained stably low during follow-up.
C1 [Hayakawa, Jun; Washington, Kareem; Uchida, Naoya; Phang, Oswald; Kang, Elizabeth M.; Hsieh, Matthew M.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hayakawa, Jun; Washington, Kareem; Uchida, Naoya; Phang, Oswald; Kang, Elizabeth M.; Hsieh, Matthew M.; Tisdale, John F.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Hayakawa, J (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
FU intramural research program of the National Institute of Diabetes,
Digestive, and Kidney Diseases; National Heart, Lung, and Blood
Institute of the National Institutes of Health
FX This work was supported by the intramural research program of the
National Institute of Diabetes, Digestive, and Kidney Diseases and the
National Heart, Lung, and Blood Institute of the National Institutes of
Health. The funders had no role in data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 33
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Z9 8
U1 0
U2 0
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 JAN 16
PY 2009
VL 4
IS 1
AR e4211
DI 10.1371/journal.pone.0004211
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437IH
UT WOS:000265479900005
PM 19148292
ER
PT J
AU Loomba, R
Lutchman, G
Kleiner, DE
Ricks, M
Feld, JJ
Borg, BB
Modi, A
Nagabhyru, P
Sumner, AE
Liang, TJ
Hoofnagle, JH
AF Loomba, R.
Lutchman, G.
Kleiner, D. E.
Ricks, M.
Feld, J. J.
Borg, B. B.
Modi, A.
Nagabhyru, P.
Sumner, A. E.
Liang, T. J.
Hoofnagle, J. H.
TI Clinical trial: pilot study of metformin for the treatment of
non-alcoholic steatohepatitis
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; NATURAL-HISTORY; OBESE;
PLACEBO; LEPTIN; DIET
AB Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.
To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH.
Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index.
Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement.
Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.
C1 [Loomba, R.; Lutchman, G.; Feld, J. J.; Borg, B. B.; Modi, A.; Nagabhyru, P.; Liang, T. J.; Hoofnagle, J. H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Kleiner, D. E.] NIDDK, Pathol Lab, Natl Canc Inst, Bethesda, MD 20892 USA.
[Ricks, M.; Sumner, A. E.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, NIH, Bldg 10,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA.
EM hoofnaglej@extra.niddk.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX Declaration of personal interests: None. All authors had access to the
data. Analysis was conducted by the first (RL) and the senior author
(JHH). The authors thank Drs Edward Doo, Marc Ghany, Theo Heller and
Yaron Rotman, and Mrs Yoon Park of the Liver Diseases Branch, NIDDK for
the help in managing patients; Ms Francine Thomas, Radiology Department,
Clinical Center, NIH for providing help in MRI and CT measurements; Dr
Barbara Frempong, Clinical Endocrinology Branch, NIDDK, NIH for
conducting FSIGT; Dr Gloria Lena Vega, Clinical Nutrition Center,
University of Texas Medical Center, Dallas, Texas, for providing
measurements of fasting free fatty acid levels; Ms Blakeley Denkinger
and Nancy Sebring, Nutrition Service, Clinical Center, NIH for providing
nutritional counseling to the patients. Declaration of funding
interests: This study was funded in full by the intramural research
program of the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 25
TC 82
Z9 85
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JAN 15
PY 2009
VL 29
IS 2
BP 172
EP 182
DI 10.1111/j.1365-2036.2008.03869.x
PG 11
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 384ZE
UT WOS:000261781900003
PM 18945255
ER
PT J
AU Purdue, MP
Hashibe, M
Berthiller, J
La Vecchia, C
Dal Maso, L
Herrero, R
Franceschi, S
Castellsague, X
Wei, QY
Sturgis, EM
Morgenstern, H
Zhang, ZF
Levi, F
Talamini, R
Smith, E
Muscat, J
Lazarus, P
Schwartz, SM
Chen, C
Neto, JE
Wunsch, V
Zaridze, D
Koifman, S
Curado, MP
Benhamou, S
Matos, E
Szeszenia-Dabrowska, N
Olshan, AF
Lence, J
Menezes, A
Daudt, AW
Mates, IN
Pilarska, A
Fabianova, E
Rudnai, P
Winn, D
Ferro, G
Brennan, P
Boffetta, P
Hayes, RB
AF Purdue, Mark P.
Hashibe, Mia
Berthiller, Julien
La Vecchia, Carlo
Dal Maso, Luigino
Herrero, Rolando
Franceschi, Silvia
Castellsague, Xavier
Wei, Qingyi
Sturgis, Erich M.
Morgenstern, Hal
Zhang, Zuo-Feng
Levi, Fabio
Talamini, Renato
Smith, Elaine
Muscat, Joshua
Lazarus, Philip
Schwartz, Stephen M.
Chen, Chu
Eluf Neto, Jose
Wuensch-Filho, Victor
Zaridze, David
Koifman, Sergio
Curado, Maria Paula
Benhamou, Simone
Matos, Elena
Szeszenia-Dabrowska, Neonilia
Olshan, Andrew F.
Lence, Juan
Menezes, Ana
Daudt, Alexander W.
Mates, Ioan Nicolae
Pilarska, Agnieszka
Fabianova, Eleonora
Rudnai, Peter
Winn, Debbie
Ferro, Gilles
Brennan, Paul
Boffetta, Paolo
Hayes, Richard B.
TI Type of Alcoholic Beverage and Risk of Head and Neck Cancer-025EFA
Pooled Analysis Within the INHANCE Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
ID UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMAS; ORAL-CAVITY;
PHARYNGEAL CANCER; PUERTO-RICO; TOBACCO; DRINKING; SMOKING; WINE;
CONSUMPTION
AB The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for <= 5, 6-15, 16-30, and > 30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.
C1 [Purdue, Mark P.; Winn, Debbie; Hayes, Richard B.] NCI, Rockville, MD 20852 USA.
[Hashibe, Mia; Berthiller, Julien; Franceschi, Silvia; Curado, Maria Paula; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France.
[La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy.
[La Vecchia, Carlo] Univ Milan, Milan, Italy.
[Dal Maso, Luigino; Talamini, Renato] Aviano Canc Ctr, I-33081 Aviano, Italy.
[Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica.
[Castellsague, Xavier] Inst Catala Oncol, Barcelona, Spain.
[Wei, Qingyi; Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Levi, Fabio] Inst Univ Med Sociale & Prevent, CH-1005 Lausanne, Switzerland.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA.
[Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Eluf Neto, Jose; Wuensch-Filho, Victor] Univ Sao Paulo, Sao Paulo, Brazil.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
[Koifman, Sergio] Escola Nacl Suade Publ, Rio De Janeiro, Brazil.
[Benhamou, Simone] INSERM, U794, Evry, France.
[Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Lodz, Poland.
[Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Lence, Juan] Inst Oncol & Radiobiol, Havana, Cuba.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Mates, Ioan Nicolae] Univ Carol Davila, Fac Med, Bucharest, Romania.
[Pilarska, Agnieszka] Med Acad, Maxillofacial Surg Clin 2, Warsaw, Poland.
[Fabianova, Eleonora] Specialized State Hlth Inst, Banska Bystrica, Slovakia.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
RP Purdue, MP (reprint author), NCI, 6120 Execut Blvd,EPS 8111, Rockville, MD 20852 USA.
EM purduem@mail.nih.gov
RI Wunsch Filho, Victor/C-4475-2012; Inca, Inct/K-2204-2013; Zaridze,
David/K-5605-2013; Epidemiologicas, Centro de pesquisas /D-4561-2013;
Eluf-Neto, Jose/B-2522-2009; Menezes, Ana/G-7266-2012;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Castellsague Pique,
Xavier/N-5795-2014; Purdue, Mark/C-9228-2016; Benhamou,
Simone/K-6554-2015; Curado, Maria Paula/M-6200-2013; Mates, Ioan
Nicolae/E-9255-2017
OI Eluf-Neto, Jose/0000-0001-7504-2115; Castellsague Pique,
Xavier/0000-0002-0802-3595; Purdue, Mark/0000-0003-1177-3108; Curado,
Maria Paula/0000-0001-8172-2483;
FU Cancer Research, Switzerland [AKT 617]; Fund for Clinical Research
Against Cancer; Gustave-Roussy Institute, Villejuif, France [88D28];
Swiss Research Against Cancer/Oncosuisse [KFS-700, OCS-1633]; World
Cancer Research Fund; European Commission's [IC15-CT98-0332]; National
Institutes of Health (NIH) [R01CA048896, R01DE012609]; NIH NIDCR
[R01DE11979]; NIDCR [R01DE13110]; NIH FIRCA; Veterans Affairs Merit
Review Funds; NIH [R01CA61188, P01CA068384, K07CA104231, P50CA90388,
R01DA11386, R03CA77954, T32CA09142, U01CA96134, R21ES011667, R01ES11740,
R01CA100264]; National Institute of Environmental Health Sciences
[P30ES010126]; UCLA Jonsson Comprehensive Cancer Center; National Cancer
Institute; Fondo para la Investigacion Cientifica y Tecnologica
(Argentina); Institut Municipal d'Invesigacio Medica (Barcelona);
Fundacxao de Amparo a Pesquisa no Estado de Sao Paulo [01/01768-2];
European Commission [IC18-CT97-0222]; International Agency for Research
on Cancer (IARC); Fondo de Investigaciones Sanitarias of the Spanish
government [FIS 97/0024, FIS 97/0662, BAE 01/5013]; International Union
Against Cancer; Yamagiwa-Yoshida Memorial International Cancer Study;
Associazione Italiana per la Ricerca sul Cancro
FX The individual studies were funded by the following sources: 1) Milan
study (Italian Association for Research on Cancer (AIRC)); 2) Aviano and
Italy multicenter studies (AIRC, Italian League Against Cancer, and
Italian Ministry of Research); 3) French study (Swiss Cancer League,
Switzerland (KFS1069-09-2000); League Against Cancer of Fribourg,
Switzerland (FOR381.88); Cancer Research, Switzerland (AKT 617); and
Fund for Clinical Research Against Cancer, Gustave-Roussy Institute,
Villejuif, France (88D28)); 4) Swiss study (Swiss League Against Cancer
and the Swiss Research Against Cancer/Oncosuisse (KFS-700 and OCS-
1633)); 5) Central Europe study (World Cancer Research Fund and the
European Commission's INCOCOPERNICUS Program (contract no.
IC15-CT98-0332)); 6) Seattle study (National Institutes of Health (NIH)
(R01CA048896 and R01DE012609)); 7) Iowa study (NIH NIDCR R01DE11979,
NIDCR R01DE13110, NIH FIRCA TW01500, and Veterans Affairs Merit Review
Funds); 8) North Carolina study (NIH grant R01CA61188 and in part by a
grant from the National Institute of Environmental Health Sciences
(P30ES010126)); 9) Tampa study (NIH P01CA068384 and K07CA104231); 10)
Los Angeles study (NIH grants P50CA90388, R01DA11386, R03CA77954,
T32CA09142, U01CA96134, and R21ES011667, as well as the Alper Research
Program for Environmental Genomics of the UCLA Jonsson Comprehensive
Cancer Center); 11) Houston study (NIH R01ES11740 and R01CA100264); 12)
Puerto Rico study (funded by the Intramural Research Program of the US
National Institutes of Health (National Cancer Institute)); 13) Latin
America study (Fondo para la Investigacion Cientifica y Tecnologica
(Argentina), Institut Municipal d'Invesigacio Medica (Barcelona),
Fundacxao de Amparo a Pesquisa no Estado de Sao Paulo (no. 01/01768-2),
and European Commission (IC18-CT97-0222)); and 14) International Agency
for Research on Cancer (IARC) Multicenter Study (Fondo de
Investigaciones Sanitarias of the Spanish government (FIS 97/0024, FIS
97/0662, and BAE 01/5013), International Union Against Cancer, and
Yamagiwa-Yoshida Memorial International Cancer Study grant). Conflict of
interest: none declared.
NR 45
TC 44
Z9 45
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 15
PY 2009
VL 169
IS 2
BP 132
EP 142
DI 10.1093/aje/kwn306
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 395IQ
UT WOS:000262518200002
PM 19064644
ER
PT J
AU Wang, R
Zhang, YW
Lan, Q
Holford, TR
Leaderer, B
Zahm, SH
Boyle, P
Dosemeci, M
Rothman, N
Zhu, Y
Qin, Q
Zheng, TZ
AF Wang, Rong
Zhang, Yawei
Lan, Qing
Holford, Theodore R.
Leaderer, Brian
Zahm, Shelia Hoar
Boyle, Peter
Dosemeci, Mustafa
Rothman, Nathaniel
Zhu, Yong
Qin, Qin
Zheng, Tongzhang
TI Occupational Exposure to Solvents and Risk of Non-Hodgkin Lymphoma in
Connecticut Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
ID UNITED-STATES; ORGANIC-SOLVENTS; NONDIFFERENTIAL MISCLASSIFICATION;
BENZENE EXPOSURE; WORKERS; MORTALITY; FORMALDEHYDE; CANCER; COHORT; MEN
AB A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996-2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), average probability (P < 0.01), cumulative intensity (P = 0.01), and cumulative probability (P < 0.01) level of organic solvent and with average probability level (P = 0.02) and cumulative intensity level of chlorinated solvent (P = 0.02). Analyses by NHL subtype showed a risk pattern for diffuse large B-cell lymphoma similar to that for overall NHL, with stronger evidence of an association with benzene exposure. Results suggest an increased risk of NHL associated with occupational exposure to organic solvents for women.
C1 [Wang, Rong; Zhang, Yawei; Leaderer, Brian; Zhu, Yong; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, New Haven, CT 06520 USA.
[Lan, Qing; Zahm, Shelia Hoar; Dosemeci, Mustafa; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Div Biostat, New Haven, CT USA.
[Boyle, Peter] Int Agcy Res Canc, F-69372 Lyon, France.
[Qin, Qin] Univ S Maine, Maine Ctr Toxicol & Environm Hlth, Portland, ME USA.
RP Zheng, TZ (reprint author), Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, 60 Coll St,LEPH 427,POB 208034, New Haven, CT 06520 USA.
EM tongzhang.zheng@yale.edu
RI Wang, Rong/H-3112-2011; Boyle, Peter/A-4380-2014; Zahm,
Shelia/B-5025-2015
OI Wang, Rong/0000-0002-2169-4174; Boyle, Peter/0000-0001-6251-0610;
FU National Cancer Institute [CA62006]; National Institutes of Health [5
D43 TW007864]
FX Author affiliations: Division of Environmental Health Sciences, Yale
University School of Public Health, New Haven, Connecticut (Rong Wang,
Yawei Zhang, Brian Leaderer, Yong Zhu, Tongzhang Zheng); Division of
Cancer Epidemiology and Genetics, National Cancer Institute, Rockville,
Maryland (Qing Lan, Shelia Hoar Zahm, Mustafa Dosemeci, Nathaniel
Rothman); Division of Biostatistics, Yale University School of Public
Health, New Haven, Connecticut (Theodore R. Holford); International
Agency for Research on Cancer, Lyon, France (Peter Boyle); and Maine
Center for Toxicology and Environmental Health, University of South
Maine, Portland, Maine (Qin Qin).; This study was supported by grant
CA62006 from the National Cancer Institute. Preparation of the
manuscript for publication was partially supported by National
Institutes of Health grant 5 D43 TW007864.; Certain data used in this
study were obtained from the Connecticut Tumor Registry located in the
Connecticut Department of Public Health. The authors assume full
responsibility for analyses and interpretation of these data. The
authors thank the institutions that allowed access to diagnostic
materials and pathology reports, including the following Connecticut
hospitals: Charlotte Hungerford Hospital, Danbury Hospital, Greenwich
Hospital, Griffin Hospital, Hartford Hospital, Johnson Memorial
Hospital, Middlesex Hospital, Lawrence and Memorial Hospital, New
Britain General Hospital, Bradley Memorial Hospital, Norwalk Hospital,
St. Francis Hospital and Medical Center, St. Mary's Hospital, Hospital
of St. Raphael, St. Vincent's Medical Center, Stamford Hospital, William
W. Backus Hospital, Waterbury Hospital, Yale-New Haven Hospital,
Manchester Memorial Hospital, Rockville General Hospital, Bridgeport
Hospital, Windham Hospital, Sharon Hospital, Milford Hospital, New
Milford Hospital, Bristol Hospital, MidState Medical Center, and
Day-Kimball Hospital. Conflict of interest: none declared. Conflict of
interest: none declared.
NR 60
TC 34
Z9 35
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 15
PY 2009
VL 169
IS 2
BP 176
EP 185
DI 10.1093/aje/kwn300
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 395IQ
UT WOS:000262518200008
PM 19056833
ER
PT J
AU Khoury, MJ
Wacholder, S
AF Khoury, Muin J.
Wacholder, Sholom
TI Invited Commentary: From Genome-Wide Association Studies to
Gene-Environment-Wide Interaction Studies-025EFChallenges and
Opportunities
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID HUMAN-DISEASES; EPIDEMIOLOGY; GENOTYPE; MEDICINE; BIOLOGY; CANCER; RISK
AB The recent success of genome-wide association studies in finding susceptibility genes for many common diseases presents tremendous opportunities for epidemiologic studies of environmental risk factors. Analysis of gene-environment interactions, included in only a small fraction of epidemiologic studies until now, will begin to accelerate as investigators integrate analyses of genome-wide variation and environmental factors. Nevertheless, considerable methodological challenges are involved in the design and analysis of gene-environment interaction studies. The authors review these issues in the context of evolving methods for assessing interactions and discuss how the current agnostic approach to interrogating the human genome for genetic risk factors could be extended into a similar approach to gene-environment-wide interaction studies of disease occurrence in human populations.
C1 [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA 30341 USA.
[Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, 4770 Buford Highway,MS K-89, Atlanta, GA 30341 USA.
EM muk1@cdc.gov
FU Intramural NIH HHS
NR 32
TC 98
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U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 15
PY 2009
VL 169
IS 2
BP 227
EP 230
DI 10.1093/aje/kwn351
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 395IQ
UT WOS:000262518200014
PM 19022826
ER
PT J
AU Chatterjee, N
Wacholder, S
AF Chatterjee, Nilanjan
Wacholder, Sholom
TI Invited Commentary: Efficient Testing of Gene-Environment Interaction
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID DESIGNS
AB Gene-environment-wide interaction studies of disease occurrence in human populations may be able to exploit the same agnostic approach to interrogating the human genome used by genome-wide association studies. The authors discuss 2 methods for taking advantage of possible independence between a single nucleotide polymorphism they call G (a genetic factor) and an environmental factor they call E while maintaining nominal type I error in studying G-E interaction when information on many genes is available. The first method is a simple 2-step procedure for testing the null hypothesis of no multiplicative interaction against the alternative hypothesis of a multiplicative interaction between an E and at least one of the markers genotyped in a genome-wide association study. The added power for the method derives from a clever work-around of a multiple testing procedure. The second is an empirical-Bayes-style shrinkage estimation framework for G-E interaction and the associated tests that can gain efficiency and power when the G-E independence assumption is met for most G's in the underlying population and yet, unlike the case-only method, is resistant to increased type I error when the underlying assumption of independence is violated. The development of new approaches to testing for interaction is an example of methodological progress leading to practical advantages.
C1 [Chatterjee, Nilanjan; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Chatterjee, N (reprint author), 6120 Execut Blvd,EPS 8020, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov
FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL091172-01]
NR 10
TC 14
Z9 14
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 15
PY 2009
VL 169
IS 2
BP 231
EP 233
DI 10.1093/aje/kwn352
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 395IQ
UT WOS:000262518200015
PM 19022825
ER
PT J
AU Cho, HY
Imani, F
Miller-DeGraff, L
Walters, D
Melendi, GA
Yamamoto, M
Polack, FP
Kleeberger, SR
AF Cho, Hye-Youn
Imani, Farhad
Miller-DeGraff, Laura
Walters, Dianne
Melendi, Guillermina A.
Yamamoto, Masayuki
Polack, Fernando P.
Kleeberger, Steven R.
TI Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial
Virus Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE airway; oxidative stress; antioxidant response element; inflammation;
sulforaphane
ID TRANSCRIPTION FACTOR NRF2; BROCCOLI SPROUT EXTRACTS; SMOKE-INDUCED
EMPHYSEMA; MUCOUS CELL METAPLASIA; NRF2-DEFICIENT MICE; QUANTITATIVE
HISTOCHEMISTRY; ENHANCES SUSCEPTIBILITY; INTERFERON-GAMMA;
GENE-EXPRESSION; ENZYME GENES
AB Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. The transcription factor Nrf2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene induction.
Objectives: The current study was designed to determine the role of Nrf2-mediated cytoprotective mechanisms in murine airway RSV disease.
Methods: Nrf2-deficient (Nrf 2(-/-)) and wild-type (Nrf 2(+/+)) mice were intranasally instilled with RSV or vehicle. In a separate study, Nrf 2(+/+) and Nrf2(-/-) mice were treated orally with sulforaphane (an Nrf 2-ARE inducer) or phosphate-buffered saline before RSV infection.
Measurements and Main Results: RSV-induced bronchopulmonary inflammation, epithelial injury, and mucus cell metaplasia as well as nasal epithelial injury were significantly greater in Nrf2(-/-) mice than in Nrf2(+/+) mice. Compared with Nrf2(+/+) mice, significantly attenuated viral clearance and IFN-gamma, body weight loss, heightened protein/lipid oxidation, and AP-1/NF-kappa B activity along with suppressed antioxidant induction was found in Nrf2(-/-) mice in response to RSV. Sulforaphane pretreatment significantly limited lung RSV replication and virus-induced inflammation in Nrf2(+/+) but not in Nrf2(-/-) mice.
Conclusions: The results of this study support an association of oxidant stress with RSV pathogenesis and a key role for the Nrf 2-ARE pathway in host defense against RSV.
C1 [Cho, Hye-Youn; Imani, Farhad; Miller-DeGraff, Laura; Walters, Dianne; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Melendi, Guillermina A.; Polack, Fernando P.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Melendi, Guillermina A.; Polack, Fernando P.] INFANT Fdn, Buenos Aires, DF, Argentina.
[Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan.
RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, Bldg 101,MD D-201,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cho2@niehs.nih.gov
RI Yamamoto, Masayuki/A-4873-2010;
OI Walters, Dianne/0000-0003-3888-2646
FU Intramural Research program of the National Institute of Environmental
Health Sciences; National Institutes of Health, Department of Health and
Human Services
FX Supported by the Intramural Research program of the National Institute
of Environmental Health Sciences, National Institutes of Health,
Department of Health and Human Services.
NR 63
TC 71
Z9 72
U1 1
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JAN 15
PY 2009
VL 179
IS 2
BP 138
EP 150
DI 10.1164/rccm.200804-535OC
PG 13
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 394PC
UT WOS:000262458000011
PM 18931336
ER
PT J
AU Fan, MQ
Bell, AR
Bell, DR
Clode, S
Fernandes, A
Foster, PMD
Fry, JR
Jiang, T
Loizou, G
MacNicoll, A
Miller, BG
Rose, M
Shaikh-Omar, O
Tran, L
White, S
AF Fan, Ming Qi
Bell, Alex R.
Bell, David R.
Clode, Sally
Fernandes, Alwyn
Foster, Paul M. D.
Fry, Jeffrey R.
Jiang, Tao
Loizou, George
MacNicoll, Alan
Miller, Brian G.
Rose, Martin
Shaikh-Omar, Osama
Tran, Lang
White, Shaun
TI Recombinant expression of aryl hydrocarbon receptor for quantitative
ligand-binding analysis
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Dioxin; PCB; Ligand binding; Aryl hydrocarbon receptor; Species
difference
ID AH-RECEPTOR; DIOXIN RECEPTOR; NUCLEAR TRANSLOCATOR; MICE LACKING;
IN-VIVO; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; PROTEIN; HSP90;
INDUCTION; AFFINITY
AB Recombinant expression of the aryl hydrocarbon receptor (AhR) yields small amounts of ligand-binding-competent AhR. Therefore. Spodoptera frugiperda (Sf9) cells and baculovirus have been evaluated for high-level and functional expression of AhR. Rat and human AhR were expressed as soluble protein in significant amounts. Expression of ligand-binding-competent AhR was sensitive to the protein concentration of Sf9 extract, and coexpression of the chaperone p23 failed to affect the yield Of functional ligand-binding AhR. The expression system yielded high levels of functional protein. with the ligand-binding capacity (B(max)) typically 20-fold higher than that obtained with rat liver cytosol. Quantitative estimates of the ligand-binding affinity Of human and rat AhR were obtained; the K(d) for recombinant rat AhR was indistinguishable from that of native rat AhR, thereby validating the expression system as a faithful model for native AhR. The human AhR bound TCDD with significantly lower affinity than the rat AhR. These findings demonstrate high-level expression of ligand-binding-competent AhR, and sufficient AhR for quantitative analysis of ligand binding. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Fan, Ming Qi; Bell, David R.; Jiang, Tao; Shaikh-Omar, Osama] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England.
[Miller, Brian G.; Tran, Lang] Inst Occupat Med, Edinburgh EH14 4AP, Midlothian, Scotland.
[Loizou, George] Hlth & Safety Lab, Buxton SK17 9JN, Derby, England.
[Fernandes, Alwyn; MacNicoll, Alan; Rose, Martin; White, Shaun] Cent Sci Lab, York YO41 1LZ, N Yorkshire, England.
[Bell, Alex R.] AstraZeneca Plc, Alderley Pk, Macclesfield SK10 4TJ, Cheshire, England.
[Clode, Sally] Covance Labs Ltd, Harrogate HG3 1PY, N Yorkshire, England.
[Foster, Paul M. D.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Fry, Jeffrey R.] Univ Nottingham, Queens Med Ctr, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England.
RP Bell, DR (reprint author), Univ Nottingham, Sch Biol, Univ Pk, Nottingham NG7 2RD, England.
EM david.bell@nottingham.ac.uk
OI Rose, Martin/0000-0001-7071-180X
FU UK Food Standards Agencyx [T01034]
FX This work was funded by a contract (T01034) from the UK Food Standards
Agency. The authors thank Declan Brady for expert technical assistance,
and John Fenlon for help in preparing the AhR antibody. We acknowledge
the Food Standards Agency and its expert reviewers (Professors G.
Gibson, A.G. Renwick, and Dr. A.G. Smith) for helpful comments and
guidance, and Lesa Aylward for helpful comments on the manuscript. We
thank Susan Moran and Christopher Bradfield for the gift of the human
AhR cDNA, and David Toft for baculovirus containing p23.
NR 36
TC 12
Z9 12
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 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JAN 15
PY 2009
VL 384
IS 2
BP 279
EP 287
DI 10.1016/j.ab.2008.10.003
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 384VQ
UT WOS:000261772700011
PM 18938125
ER
PT J
AU Cismasiu, VB
Duque, J
Paskaleva, E
Califano, D
Ghanta, S
Young, HA
Avram, D
AF Cismasiu, Valeriu B.
Duque, Javier
Paskaleva, Elena
Califano, Danielle
Ghanta, Sailaja
Young, Howard A.
Avram, Dorina
TI BCL11B enhances TCR/CD28-triggered NF-kappa B activation through
up-regulation of Cot kinase gene expression in T-lymphocytes
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE BCL11B; cancer Osaka thyroid oncogene (Cot) kinase; C-terminal binding
protein-interacting protein 2 (CTIP2); nuclear factor kappa B (NF-kappa
B); T-cell receptor (TCR) signalling
ID TRANSCRIPTION FACTOR; PROMOTER ACTIVATION; INTERLEUKIN-2 GENE; RESPONSE
ELEMENT; NUCLEAR-FACTOR; IL-2 PROMOTER; CELL-LINES; ALPHA-GENE; C-REL;
CD28
AB BCL11B is a Transcriptional regulator with all important role in T-cell development and leukaemogenesis. We demonstrated recently that BCL11B controls expression from the IL (interleukin)-2 promoter through direct binding to file USI (upstream site 1). fit the present study, we provide evidence that BCL11B also participates in the activation of IL-2 gene expression by enhancing NF-kappa B (nuclear factor kappa B) activity in the context of TCR (T-cell receptor)/CD28-triggered T-cell activation. Enhanced NF-kappa B activation is not a consequence of BCL11B binding to file NF-kappa B response elements or association with the NF-kappa B-DNA complexes, but rather the result of higher translocation of NF-kappa B to the nucleus Caused by enhanced degradation Of I kappa B (inhibitor of NF-kappa B). The enhanced I kappa B degradation in cells with increased levels of BCL11B wits specific for T-cells activated through the TCR, but not for cells activated through TNF alpha (tumour necrosis factor alpha) or UV light, and was caused by increased activity of I kappa B kinase, as indicated by its increase in phosphorylation. As BCL11B is a transcription factor, we investigated whether the expression of genes upstream of I kappa B kinase in the TCR/CD28 signalling pathway was affected by increased BCL11B expression, and found that Cot (cancer Osaka thyroid oncogene) kinase mRNA levels were elevated. Cot kinase is known to promote enhanced I kappa B kinase activity, which results in the phosphorylation and degradation Of I kappa B and activation of NF-kappa B. The implied involvement of Cot kinase in BCL11B-mediated NF-kappa B activation in response to TCR activation is supported by the fact that a Cot kinase dominant-negative mutant or Cot kinase siRNA (small interfering RNA) knockdown blocked BCL11B mediated NF-kappa B activation. In support Of Our observations, in the present study we report that BCL11B enhances the expression of several other NF-kappa B Target genes, in addition to IL-2. fit addition, we provide evidence that BCL11B associates with intron 2 of the Cot kinase gene to regulate its expression.
C1 [Cismasiu, Valeriu B.; Duque, Javier; Paskaleva, Elena; Califano, Danielle; Ghanta, Sailaja; Avram, Dorina] Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA.
[Young, Howard A.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Avram, D (reprint author), Albany Med Coll, Ctr Cell Biol & Canc Res, 47 New Scotland Ave,MC-165, Albany, NY 12208 USA.
EM avramd@mail.amc.edu
RI Cismasiu, Valeriu Bogdan/F-1512-2011
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [R01AI078273]; American Cancer Society
[ACS-RSG-04-265-01-MGO]
FX This work was supported by the National Institutes of Health/National
Institute of Allergy and Infectious Diseases [grant number R01AI078273];
and by the American Cancer Society [grant number ACS-RSG-04-265-01-MGO]
awarded to D.A.
NR 43
TC 22
Z9 22
U1 0
U2 1
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD JAN 15
PY 2009
VL 417
BP 457
EP 466
DI 10.1042/BJ20080925
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 401DG
UT WOS:000262918200006
PM 18831712
ER
PT J
AU Elizondo, G
Medina-Diaz, IM
Cruz, R
Gonzalez, FJ
Vega, L
AF Elizondo, Guillermo
Medina-Diaz, Irma M.
Cruz, Raymundo
Gonzalez, Frank J.
Vega, Libia
TI Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression
through the induction of GADD153-C/EBP beta interaction
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Raldh1; Retinoic acid; RAR alpha; C/EBP beta; GADD153
ID ARYL-HYDROCARBON RECEPTOR; HUMAN ALDEHYDE DEHYDROGENASE; BINDING PROTEIN
BETA; ALCOHOL-DEHYDROGENASE; NULL MICE; METABOLISM; MOUSE;
IDENTIFICATION; ANTAGONISM; ALDH1
AB Mammalian class I aldehyde dehydrogenase (ALDH) plays an important role in the biosynthesis of the hormone retinoic acid (RA), which modulates gene expression and cell differentiation. RA has been shown to mediate control of human ALDH1 gene expression through modulation of the retinoic acid receptor alpha (RAR alpha) and the CCAAT/enhancer binding protein beta (C/EBP beta). The positive activation of these transcription factors on the ALDH1 promoter is inhibited by RA through a decrease of C/EBP beta binding to the ALDH1 CCAAT box response element. However, the mechanism of this effect remains unknown. Here we report that the RAR alpha/retinoid X receptor beta (RXR beta) complex binds to the mouse retinaldehyde dehydrogenase 1 (Raldh1) promoter at a non-consensus RA response element (RARE) with similar affinity to that of the consensus RARE. We found that C/EBP beta binds to a Raldh1 CCAAT box located at -82/-58bp, adjacent to the RARE. Treatment with RA increases GADD153 and GADD153-C/EBP beta interaction resulting in a decreased cellular availability of C/EBP beta for binding to the Raldh1 CCAAT box. These data support a model in which high RA levels inhibit Raldh1 gene expression by sequestering C/EBP beta through its interaction to GADD153. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Elizondo, Guillermo] CINVESTAV, Dept Cell Biol, Mexico City 07360, DF, Mexico.
[Medina-Diaz, Irma M.] Autonomous Univ Nayarit, Lab Environm & Toxicol Anal, Nayarit, Mexico.
[Cruz, Raymundo; Vega, Libia] CINVESTAV, Toxicol Sect, Mexico City 07360, DF, Mexico.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Elizondo, G (reprint author), CINVESTAV, Dept Cell Biol, Av IPN 2508, Mexico City 07360, DF, Mexico.
EM gazuela@cinvestav.mx
RI Vega, Libia/C-3391-2013
OI Vega, Libia/0000-0002-4993-5267
FU Intramural NIH HHS [Z01 BC005561-21]
NR 44
TC 20
Z9 20
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD JAN 15
PY 2009
VL 77
IS 2
BP 248
EP 257
DI 10.1016/j.bcp.2008.10.011
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 394ZW
UT WOS:000262492700012
PM 18992716
ER
PT J
AU Pugalenthi, G
Tang, K
Suganthan, PN
Chakrabarti, S
AF Pugalenthi, Ganesan
Tang, Ke
Suganthan, P. N.
Chakrabarti, Saikat
TI Identification of structurally conserved residues of proteins in absence
of structural homologs using neural network ensemble
SO BIOINFORMATICS
LA English
DT Article
ID SEQUENCE; SUPERFAMILIES; DATABASE; MOTIFS; REGIONS; ALIGNMENTS;
ALGORITHM; FAMILIES; SERVER; TOOLS
AB Motivation: So far various bioinformatics and machine learning techniques applied for identification of sequence and functionally conserved residues in proteins. Although few computational methods are available for the prediction of structurally conserved residues from protein structure, almost all methods require homologous structural information and structure-based alignments, which still prove to be a bottleneck in protein structure comparison studies. In this work, we developed a neural network approach for identification of structurally important residues from a single protein structure without using homologous structural information and structural alignment.
Results: A neural network ensemble ( NNE) method that utilizes negative correlation learning ( NCL) approach was developed for identification of structurally conserved residues ( SCRs) in proteins using features that represent amino acid conservation and composition, physico-chemical properties and structural properties. The NCL-NNE method was applied to 6042 SCRs that have been extracted from 496 protein domains. This method obtained high prediction sensitivity ( 92.8%) and quality ( Matthew's correlation coefficient is 0.852) in identification of SCRs. Further benchmarking using 60 protein domains containing 1657 SCRs that were not part of the training and testing datasets shows that the NCL-NNE can correctly predict SCRs with similar to 90% sensitivity. These results suggest the usefulness of NCL-NNE for facilitating the identification of SCRs utilizing information derived from a single protein structure. Therefore, this method could be extremely effective in large-scale benchmarking studies where reliable structural homologs and alignments are limited.
C1 [Pugalenthi, Ganesan; Suganthan, P. N.] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore.
[Tang, Ke] Univ Sci & Technol China, Dept Comp Sci & Technol, Hefei 230026, Anhui, Peoples R China.
[Chakrabarti, Saikat] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Suganthan, PN (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore.
RI Suganthan, .Ponnuthurai /A-5023-2011; Tang, Ke/E-5656-2015
OI Suganthan, .Ponnuthurai /0000-0003-0901-5105;
FU Agency for Science, Technology and Research; National Natural Science
Foundation of China [60802036]; National Institutes of Health/DHHS
FX Funding: A*Star (Agency for Science, Technology and Research to G. P.
and P. N. S.); National Natural Science Foundation of China grant ( No.
60802036 to K. T.); Intramural Research Program of the National Library
of Medicine at National Institutes of Health/DHHS ( to S. C.).
NR 31
TC 10
Z9 10
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JAN 15
PY 2009
VL 25
IS 2
BP 204
EP 210
DI 10.1093/bioinformatics/btn618
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 395IR
UT WOS:000262518300008
PM 19038986
ER
PT J
AU Tarter, RE
Kirisci, L
Gavaler, JS
Reynolds, M
Kirillova, G
Clark, DB
Wu, JL
Moss, HB
Vanyukov, M
AF Tarter, Ralph E.
Kirisci, Levent
Gavaler, Judith S.
Reynolds, Maureen
Kirillova, Galina
Clark, Duncan B.
Wu, Jionglin
Moss, Howard B.
Vanyukov, Michael
TI Prospective Study of the Association Between Abandoned Dwellings and
Testosterone Level on the Development of Behaviors Leading to Cannabis
Use Disorder in Boys
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Cannabis; etiology; hormones; marijuana; neighborhood; substance abuse
ID SUBSTANCE USE DISORDERS; USE SCREENING INVENTORY; EARLY ADOLESCENCE;
DRUG-USE; PSYCHOLOGICAL DISTRESS; CONTEXTUAL FACTORS; SEXUAL-MATURATION;
NEIGHBORHOOD; PERSONALITY; AGGRESSION
AB Background: The role of testosterone in the development of behaviors presaging cannabis use and subsequently cannabis use disorder was investigated in a prospective study of 208 boys. It was theorized that adverse neighborhood correlates with testosterone level that in turn potentiates behaviors predisposing to cannabis consumption and subsequently diagnosis of cannabis use disorder.
Methods: Proportion of boarded-up dwellings in the 1990 census tract and testosterone level were recorded at baseline (ages 10-12), followed by assessments of assaultiveness and testosterone level (ages 12-14), social dominance/norm-violating behavior(SDNVB) (age 16), cannabis use (age 19), and cannabis use disorder (age 22).
Results: Percent of vacant dwellings correlates with testosterone level that in turn predicts assaultive behavior sequentially leading to SDNVB, cannabis use, and cannabis use disorder. Externalizing behaviors and cannabis use disorder are not directly predicted by neighborhood quality.
Conclusions: Elevated testosterone level intermediates the association between neighborhood adversity and aggressive socially deviant behaviors presaging cannabis use and cannabis use disorder.
C1 [Tarter, Ralph E.; Kirisci, Levent; Gavaler, Judith S.; Reynolds, Maureen; Kirillova, Galina; Clark, Duncan B.; Vanyukov, Michael] Univ Pittsburgh, Sch Pharm, Ctr Educ & Drug Abuse Res, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Wu, Jionglin] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
[Moss, Howard B.] NIAAA, Bethesda, MD USA.
RP Tarter, RE (reprint author), Univ Pittsburgh, Sch Pharm, Ctr Educ & Drug Abuse Res, Dept Pharmaceut Sci, 711 Salk Hall, Pittsburgh, PA 15261 USA.
EM tarter@pitt.edu
FU National Institute on Drug Abuse [DA05605, K02-DA018701, K02-DA017822]
FX This study was supported by Grants DA05605, K02-DA018701, and
K02-DA017822 from the National Institute on Drug Abuse.
NR 49
TC 17
Z9 17
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 15
PY 2009
VL 65
IS 2
BP 116
EP 121
DI 10.1016/j.biopsych.2008.08.032
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 391KB
UT WOS:000262231100004
PM 18930183
ER
PT J
AU Shippenberg, TS
Chefer, VI
Thompson, AC
AF Shippenberg, Toni S.
Chefer, Vladimir I.
Thompson, Alexis C.
TI Delta-Opioid Receptor Antagonists Prevent Sensitization to the
Conditioned Rewarding Effects of Morphine
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Conditioned place preference; delta opioid receptor; morphine;
naltrindole; naltriben; sensitization
ID PLACE PREFERENCE; KNOCKOUT MICE; DELTA(1)-OPIOID RECEPTOR; MEDIATED
ANTINOCICEPTION; NALTRINDOLE; KAPPA; MU; DEPENDENCE; TOLERANCE; SUBTYPES
AB Background: Functional interactions between mu- and delta-opioid receptors (MOPr and DOPr, respectively) are implicated in morphine tolerance and dependence.The contribution of DOPr to the conditioned rewarding effects of morphine and the enhanced conditioned response that occurs after repeated morphine administration is unknown.This issue was addressed with the conditioned place preference procedure (CPP).
Methods: Rats received home cage injections of saline or morphine (5.0 mg/kg/day X 5 days) before conditioning. For sensitization studies, DOPr antagonists (DOPr1/2: naltrindole, DOPr2: naltriben, D0Pr1: 7-benzylidenenaltrexone) were administered before morphine injections. Conditioning sessions (2 morphine; 2 saline) commenced 3 days later, To assess the influence of acute DOPr blockade on the conditioning of morphine reward in naive animals, 3 morphine and 3 saline conditioning sessions were employed. Antagonists were administered before morphine conditioning sessions.
Results: Morphine was ineffective as a conditioning stimulus after two conditioning sessions in naive rats. However, doses >= 3.0 mg/kg produced significant CPP in morphine pre-exposed rats, confirming that sensitization develops to the conditioned rewarding effects of morphine. In animals that received morphine pre-exposure with naltrindole or naltriben but not 7-benzylidenenaltrexone, sensitization was prevented. No attenuation of morphine CPP was observed in animals that received DOPr antagonists acutely, before conditioning sessions.
Conclusions: These data indicate a critical role of DOPr systems in mediating sensitization to the conditioned rewarding effects of morphine. The efficacy of naltrindole and naltriben in preventing the enhanced response to morphine suggest the specific involvement of DOPr2 in the sensitization process.
C1 [Shippenberg, Toni S.; Chefer, Vladimir I.] NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Thompson, Alexis C.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA.
RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH,US Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tshippen@intra.nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 44
TC 41
Z9 41
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 15
PY 2009
VL 65
IS 2
BP 169
EP 174
DI 10.1016/j.biopsych.2008.09.009
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 391KB
UT WOS:000262231100012
PM 18950747
ER
PT J
AU Phelps, LE
Brutsche, N
Moral, JR
Luckenbaugh, DA
Manji, HK
Zarate, CA
AF Phelps, Laura E.
Brutsche, Nancy
Moral, Jazmin R.
Luckenbaugh, David A.
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI Family History of Alcohol Dependence and Initial Antidepressant Response
to an N-methyl-D-aspartate Antagonist
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Alcohol dependence; depression; family history; glutamate; ketamine;
NMDA receptor
ID ASTERISK-D COHORT; MOOD DISORDERS; RATING-SCALE; MICE LACKING; KETAMINE;
DEPRESSION; NEUROTRANSMISSION; SUBUNIT
AB Background: A high rate of comorbidity exists between mood disorders and alcohol dependence. Furthermore, both ketamine, a dissociative anesthetic with a recently described rapid-onset antidepressant effect, and ethanol are N-methyl-D-aspartate (NMDA) receptor antagonists. Previous investigations of healthy individuals with a family history of alcohol dependence have found that these individuals have an attenuated response to ketamine's perceptual disturbance and dysphoric effects similar to that found in individuals with a self-reported history of alcohol dependence. This study investigated whether a family history of alcohol dependence influences ketamine's initial antidepressant effect.
Methods: Twenty-six subjects with DSM-IV treatment-resistant major depression were given an open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg) and rated using various depression scales at baseline, 40, 80,120, and 230 min postinfusion. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Results: Subjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.
Conclusions: A family history of alcohol dependence appears to predict a rapid initial antidepressant response to an NMDA receptor antagonist.
C1 NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
Dept Hlth & Human Serv, Bethesda, MD USA.
RP Zarate, CA (reprint author), 10 Ctr Dr,CRC,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Intramural Research Program
FX This study was supported by the Intramural Research Program at the
National Institute of Mental Health and the National Alliance for
Research on Schizophrenia and Depression (to CZ). Ioline Henter provided
invaluable editoral assistance.
NR 21
TC 108
Z9 112
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 15
PY 2009
VL 65
IS 2
BP 181
EP 184
DI 10.1016/j.biopsych.2008.09.029
PG 4
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 391KB
UT WOS:000262231100014
PM 18996507
ER
PT J
AU Boswell, CA
Regino, CAS
Baidoo, KE
Wong, KJ
Milenic, DE
Kelley, JA
Lai, CC
Brechbiel, MW
AF Boswell, C. Andrew
Regino, Celeste A. S.
Baidoo, Kwamena E.
Wong, Karen J.
Milenic, Diane E.
Kelley, James A.
Lai, Christopher C.
Brechbiel, Martin W.
TI A novel side-bridged hybrid phosphonate/acetate pendant cyclam:
Synthesis, characterization, and (64)Cu small animal PET imaging
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Positron emission tomography; Copper-64; Side-bridged cyclam;
Bifunctional chelating agent
ID IN-VIVO; MACROCYCLIC LIGANDS; THERMODYNAMIC STABILITY; COPPER(II)
COMPLEXES; MONOCLONAL-ANTIBODY; DERIVATIVES; LYMPHOMA; LYM-1; MICE;
1,4,8,11-TETRAAZACYCLOTETRADECANE
AB Copper-64 (t(1/2) = 12.7 h; beta(+): 0.653 MeV, 17.4%; beta: 0.578 MeV, 39%) is produced in a biomedical cyclotron and has applications in both imaging and therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind copper radionuclides to antibodies and peptides owing to their relatively high kinetic stability. A novel side-bridged cyclam featuring both pendant acetate and phosphonate groups was synthesized using a Kabachnik-Fields approach followed by hydrobromic acid deprotection. The Cu(II) complex of the novel ligand was synthesized, radiolabeling with (64)Cu was demonstrated, and in vitro (serum) stability was performed. In addition, in vivo distribution and clearance of the (64)Cu-labeled complex was visualized by positron emission tomography (PET) imaging. This novel chelate may be useful in (64)Cu-mediated diagnostic positron emission tomography (PET) imaging as well as targeted radiotherapeutic applications. Published by Elsevier Ltd.
C1 [Boswell, C. Andrew; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Regino, Celeste A. S.; Wong, Karen J.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kelley, James A.; Lai, Christopher C.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
OI Boswell, Charles/0000-0002-0426-9846
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 39
TC 27
Z9 27
U1 1
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JAN 15
PY 2009
VL 17
IS 2
BP 548
EP 552
DI 10.1016/j.bmc.2008.11.073
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 398CF
UT WOS:000262708300013
PM 19101152
ER
PT J
AU Choi, HK
Choi, S
Lee, Y
Kang, DW
Ryu, H
Maeng, HJ
Chung, SJ
Pavlyukovets, VA
Pearce, LV
Toth, A
Tran, R
Wang, Y
Morgan, MA
Blumberg, PM
Lee, J
AF Choi, Hyun-Kyung
Choi, Sun
Lee, Yoonji
Kang, Dong Wook
Ryu, HyungChul
Maeng, Han-Joo
Chung, Suk-Jae
Pavlyukovets, Vladimir A.
Pearce, Larry V.
Toth, Attila
Tran, Richard
Wang, Yun
Morgan, Matthew A.
Blumberg, Peter M.
Lee, Jeewoo
TI Non-vanillyl resiniferatoxin analogues as potent and metabolically
stable transient receptor potential vanilloid 1 agonists
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Resiniferatoxin; TRPV1 agonist
ID ANALGESIC AGENTS; IODO-RESINIFERATOXIN; CAPSAICIN RECEPTOR; GANGLION
NEURONS; VR1; ANTAGONIST; BINDING; TRPV1; RTX; DESENSITIZATION
AB A series of non-vanillyl resiniferatoxin analogues, having 4-methylsulfonylaminophenyl and fluorophenyl moieties as vanillyl surrogates, have been investigated as ligands for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Although lacking the metabolically problematic 4-hydroxy substituent on the A-region phenyl ring, the compounds retained substantial agonist potency. Indeed, the 3-methoxy-4-methylsulfonylaminophenyl analog (1) was modestly (2.5-fold) more potent than RTX, with an EC(50) = 0.106 nM. Further, it resembled RTX in its kinetics and pattern of stimulation of the levels of intracellular calcium in individual cells, as revealed by imaging. Compound 1 displayed modestly enhanced in vitro stability in rat liver microsomes and in plasma, suggesting that it might be a pharmacokinetically more favorable surrogate of resiniferatoxin. Molecular modeling analyses with selected analogues provide evidence that the conformational differences could affect their binding affinities, especially for the ester versus amide at the B-region. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Choi, Hyun-Kyung; Kang, Dong Wook; Ryu, HyungChul; Maeng, Han-Joo; Chung, Suk-Jae; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Choi, Sun; Lee, Yoonji] Ewha Womans Univ, Coll Pharm, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
[Choi, Sun; Lee, Yoonji] Ewha Womans Univ, Natl Core Res Ctr Cell Signaling & Drug Discovery, Seoul 120750, South Korea.
[Pavlyukovets, Vladimir A.; Pearce, Larry V.; Toth, Attila; Tran, Richard; Wang, Yun; Morgan, Matthew A.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
RI Toth, Attila/F-4859-2010
OI Toth, Attila/0000-0001-6503-3653
FU Korea Science and Engineering Foundation (KOSEF) [R11-2007-107-02001-0,
R01-2007-000-20052-0]; Ministry of Education, Science and Technology
[R15-2006-020]; KOSEF; National Institutes of Health, Center for Cancer
Research, National Cancer Institute
FX This research was supported by Grants R11-2007-107-02001-0 and
R01-2007-000-20052-0 from the Korea Science and Engineering Foundation
(KOSEF), the National Core Research Center program (No. R15-2006-020) of
the Ministry of Education, Science and Technology and KOSEF through the
Center for Cell Signaling & Drug Discovery Research at Ewha Womans
University, and by the Intramural Research Program of the National
Institutes of Health, Center for Cancer Research, National Cancer
Institute.
NR 32
TC 5
Z9 5
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JAN 15
PY 2009
VL 17
IS 2
BP 690
EP 698
DI 10.1016/j.bmc.2008.11.085
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 398CF
UT WOS:000262708300031
PM 19135377
ER
PT J
AU Galal, AM
Gul, W
Slade, D
Ross, SA
Feng, S
Hollingshead, MG
Alley, MC
Kaur, G
ElSohly, MA
AF Galal, Ahmed M.
Gul, Waseem
Slade, Desmond
Ross, Samir A.
Feng, Shixia
Hollingshead, Melinda G.
Alley, Michael C.
Kaur, Gurmeet
ElSohly, Mahmoud A.
TI Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene
acetal dimers showing anticancer and antiprotozoal activity
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Artemisinin; Dihydroartemisinin; Dihydroartemisitene; Acetal dimers;
Anticancer activity; Antiangiogenesis activity; Antimalarial activity;
Antileishmanial activity
ID PLASMODIUM-FALCIPARUM MALARIA; ARTEMISININ DERIVATIVES; IN-VIVO;
TUMOR-CELLS; ANTIMALARIAL; CYTOTOXICITY; ANALOGS; DRUGS; ASSIGNMENTS;
ARTESUNATE
AB Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 mu M (most active). The significant activity of the compounds in this preliminary screen led to additional in vitro antitumor and antiangiogenesis studies. Several active dimers were also evaluated in the in vivo NCI hollow fiber assay followed by a preliminary xenograft study. The title compounds were found to be active against solid tumor-derived cell lines and showed good correlation with other artemisinin-based molecules in the NCI database. The dimers were also evaluated for their antimalarial and antileishmanial activities. The antimalarial activity ranged from 0.3 to 32 nM (IC(50)), compared to 9.9 nM for artemisinin. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Galal, Ahmed M.; Gul, Waseem; Slade, Desmond; Ross, Samir A.; ElSohly, Mahmoud A.] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
[Gul, Waseem; Feng, Shixia; ElSohly, Mahmoud A.] ElSohly Labs Inc, Oxford, MS 38655 USA.
[Ross, Samir A.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA.
[Hollingshead, Melinda G.; Alley, Michael C.; Kaur, Gurmeet] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA.
[ElSohly, Mahmoud A.] Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA.
RP Galal, AM (reprint author), Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
EM amgalalv@olemiss.edu
FU United States Department of Agriculture [58-6408-7-012]; National Cancer
Institute, National Institutes of Health [NO1-CO-12400]
FX The authors thank the United States Department of Agriculture,
Agriculture Research Service Specific Cooperative Agreement No.
58-6408-7-012, for partial support of this work. The authors are also
grateful to Mr. Frank T. Wiggers, Dr. Chuck Dunbar and Mr. John Trott
for the NMR, the HRESIFTMS analyses and conducting the antimalarial and
antileishmanial screens, respectively. This research was supported [in
part] by the Developmental Therapeutics Program of the NIH, National
Cancer Institute. This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract NO1-CO-12400. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
NCI-Frederick is accredited by AAALACi and follows the Public Health
Service Policy on the Care and Use of Laboratory Animals. Animal care
was provided in accordance with procedures outlines in the Guide for
Care and Use of Laboratory Animals (NIH publication NO. 86-23, 1985).
NR 47
TC 36
Z9 42
U1 1
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JAN 15
PY 2009
VL 17
IS 2
BP 741
EP 751
DI 10.1016/j.bmc.2008.11.050
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 398CF
UT WOS:000262708300037
PM 19084416
ER
PT J
AU Ballet, S
Feytens, D
De Wachter, R
De Vlaeminck, M
Marczak, ED
Salvadori, S
de Graaf, C
Rognan, D
Negri, L
Lattanzi, R
Lazarus, LH
Tourwe, D
Balboni, G
AF Ballet, Steven
Feytens, Debby
De Wachter, Rien
De Vlaeminck, Magali
Marczak, Ewa D.
Salvadori, Severo
de Graaf, Chris
Rognan, Didier
Negri, Lucia
Lattanzi, Roberta
Lazarus, Lawrence H.
Tourwe, Dirk
Balboni, Gianfranco
TI Conformationally constrained opioid ligands: The Dmt-Aba and Dmt-Aia
versus Dmt-Tic scaffold
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Opioid peptidomimetics; Constrained amino acids
ID RECEPTOR SELECTIVITY; EXTRACELLULAR LOOP; DELTA ANTAGONISTS; HIGHLY
POTENT; AMINO-ACIDS; CHI-SPACE; ANALOGS; PHARMACOPHORE; PEPTIDES;
BINDING
AB Replacement of the constrained phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in the opioid Dmt-Tic-Gly-NH-Bn scaffold by the 4-amino-1,2,4,5-tetrahydro-indolo[2,3-c]azepin-3-one (Aia) and 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffolds has led to the discovery of novel potent l-selective agonists (Structures 5 and 12) as well as potent and selective delta-opioid receptor antagonists (Structures 9 and 15). Both stereochemistry and N-terminal N,N-dimethylation proved to be crucial factors for opioid receptor selectivity and functional bioactivity in the investigated small pepti-domimetic templates. In addition to the in vitro pharmacological evaluation, automated docking models of Dmt-Tic and Dmt-Aba analogues were constructed in order to rationalize the observed structure activity data. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Ballet, Steven; Feytens, Debby; De Wachter, Rien; De Vlaeminck, Magali; Tourwe, Dirk] Vrije Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium.
[Marczak, Ewa D.; Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, LP, Res Triangle Pk, NC 27709 USA.
[Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy.
[de Graaf, Chris; Rognan, Didier] Univ Louis Pasteur Strasbourg 1, CNRS, UMR 7175 LC1, F-67401 Illkirch Graffenstaden, France.
[Negri, Lucia; Lattanzi, Roberta] Univ Rome, Dept Physiol & Pharmacol Vittorio Ersparmer, I-00815 Rome, Italy.
[Balboni, Gianfranco] Univ Cagliari, Dept Pharmaceut Sci, I-09124 Cagliari, Italy.
[Balboni, Gianfranco] Univ Cagliari, Ctr Biotechnol, I-09124 Cagliari, Italy.
RP Tourwe, D (reprint author), Vrije Univ Brussels, Dept Organ Chem, Pl Laan 2, B-1050 Brussels, Belgium.
EM datourwe@vub.ac.be
RI Rognan, Didier/B-9939-2014;
OI LATTANZI, Roberta/0000-0002-6377-9256; de Graaf,
Chris/0000-0002-1226-2150; SALVADORI, Severo/0000-0002-8224-2358
FU Scientific Research - Flanders (Belgium) [G.0036.04, G.0008.08]; NIH;
NIEHS; European grant 'Normolife' [LSHCCT2006-037733]
FX D. Feytens is a Research Assistant for the Fund for Scientific Research
- Flanders (Belgium). This work was supported in part by the Intramural
Research Program of NIH and NIEHS and by the Fund for Scientific
Research - Flanders ( Belgium, Grants G.0036.04 and G.0008.08) and
European grant 'Normolife' (LSHCCT2006-037733).
NR 41
TC 17
Z9 17
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JAN 15
PY 2009
VL 19
IS 2
BP 433
EP 437
DI 10.1016/j.bmcl.2008.11.051
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 386UU
UT WOS:000261908900032
PM 19062273
ER
PT J
AU Ghosh, MC
Baatar, D
Collins, G
Carter, A
Indig, F
Biragyn, A
Taub, DD
AF Ghosh, Manik C.
Baatar, Dolgor
Collins, Gary
Carter, Arnell
Indig, Fred
Biragyn, Arya
Taub, Dennis D.
TI Dexamethasone augments CXCR4-mediated signaling in resting human T cells
via the activation of the Src kinase Lck
SO BLOOD
LA English
DT Article
ID CHEMOKINE RECEPTOR CXCR4; RHO-FAMILY PROTEINS; NEGATIVE REGULATION;
ENDOTHELIAL-CELLS; GLUCOCORTICOIDS; LYMPHOCYTES; EXPRESSION; ADHESION;
PHOSPHORYLATION; MIGRATION
AB Dexamethasone (DM) is a synthetic member of the glucocorticoid ( GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly used to treat chronic inflammatory disorders, severe allergies, and other disease states. Although GCs are known to mediate well-defined transcriptional effects via GC receptors (GCR), there is increasing evidence that GCs also initiate rapid non-genomic signaling events in a variety of cell types. Here, we report that DM induces the phosphorylation of Lck and the activation of other downstream mediators, including p59Fyn, Zap70, Rac1, and Vav in resting but not activated human T cells. DM treatment also augments CXCL12-mediated signaling in resting T cells through its cell surface receptor, CXCR4 resulting in the enhanced actin polymerization, Rac activation, and cell migration on ligand exposure. Lck was found to be a critical intermediate in these DM-induced signaling activities. Moreover, DM-mediated Lck phosphorylation in T cells was dependent on the presence of both the GCR and the CD45 molecule. Overall, these results elucidate additional nongenomic effects of DM and the GCR on resting human T cells, inducing Lck and downstream kinase activation and augmenting chemokine signaling and function. (Blood. 2009; 113: 575-584)
C1 [Taub, Dennis D.] NIA, Immunol Lab, Clin Immunol Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Indig, Fred] NIA, Intramural Res Program, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
RP Taub, DD (reprint author), NIA, Immunol Lab, Clin Immunol Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM taubd@grc.nia.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health.
NR 53
TC 22
Z9 22
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JAN 15
PY 2009
VL 113
IS 3
BP 575
EP 584
DI 10.1182/blood-2008-04-151803
PG 10
WC Hematology
SC Hematology
GA 394ZO
UT WOS:000262491900014
PM 18840710
ER
PT J
AU Stockwin, LH
Vistica, DT
Kenney, S
Schrump, DS
Butcher, DO
Raffeld, M
Shoemaker, RH
AF Stockwin, Luke H.
Vistica, David T.
Kenney, Susan
Schrump, David S.
Butcher, Donna O.
Raffeld, Mark
Shoemaker, Robert H.
TI Gene expression profiling of alveolar soft-part sarcoma (ASPS)
SO BMC CANCER
LA English
DT Article
ID SKELETAL-MUSCLE DIFFERENTIATION; REGULATORY PROTEIN EXPRESSION;
TRANSCRIPTION FACTOR GENE; RENAL-CELL CARCINOMA; GROWTH-FACTOR; TFE3
GENE; MOLECULAR-CLONING; STRIATED-MUSCLE; BREAST-CANCER; BINDING
AB Background: Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.
Methods: For seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry.
Results: Analysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis (ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2), cell proliferation (PRL, IGFBP1, NTSR2, PCSK1), metastasis (ADAM9, ECM1, POSTN) and steroid biosynthesis (CYP17A1 and STS). A number of muscle-restricted transcripts (ITGB1BP3/MIBP, MYF5, MYF6 and TRIM63) were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes (MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3/MIBP and TRIM63).
Conclusion: Results from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.
C1 [Vistica, David T.; Kenney, Susan; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
[Stockwin, Luke H.] NCI, Drug Mech Grp, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Schrump, David S.] NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Butcher, Donna O.] NCI, Pathol Histotechnol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Shoemaker, RH (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
EM Stockwin@ncifcrf.gov; vistica@dtpax2.ncifcrf.gov; skenney@ncifcrf.gov;
david_schrump@nih.gov; butcherd@ncifcrf.gov; mraff@mail.nih.gov;
shoemaker@dtpax2.ncifcrf.gov
FU National Cancer Institute, National Institutes of Health [NO1-CO-12400]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. NO1-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
This research was supported [ in part] by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute. We also recognize the intellectual
contributions to this manuscript made by Dr. Ming Zhao ( NCI, Bethesda).
NR 61
TC 27
Z9 30
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JAN 15
PY 2009
VL 9
AR 22
DI 10.1186/1471-2407-9-22
PG 11
WC Oncology
SC Oncology
GA 417DF
UT WOS:000264054900002
PM 19146682
ER
PT J
AU Matrone, MA
Whipple, RA
Balzer, EM
Cho, EH
Yoon, JR
Martin, SS
AF Matrone, M. A.
Whipple, R. A.
Balzer, E. M.
Cho, E. H.
Yoon, J. R.
Martin, S. S.
TI Metastasis-associated microtentacles are induced in detached and
circulating breast tumor cells by expression of the microtubule-binding
protein, Tau
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
SU S
BP 76S
EP 76S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200050
ER
PT J
AU Matrone, MA
Whiplle, RA
Balzer, EM
Cho, EH
Yoon, JR
Martin, SS
AF Matrone, M. A.
Whiplle, R. A.
Balzer, E. M.
Cho, E. H.
Yoon, J. R.
Martin, S. S.
TI c-MYC amplification and correlation with patient outcome in early stage
HER2+breast cancer from the NCCTG adjuvant intergroup trial N9831
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 [Matrone, M. A.; Whiplle, R. A.; Balzer, E. M.; Cho, E. H.; Yoon, J. R.; Martin, S. S.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
RI Cho, Edward/B-3727-2012
OI Cho, Edward/0000-0002-0278-334X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
SU S
BP 76S
EP 77S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200051
ER
PT J
AU Ganz, PA
Land, SR
Geyer, CE
Costantino, JP
Pajon, ER
Fehrenbacher, L
Atkins, JN
Polikoff, JA
Vogel, VG
Erban, JK
Livingston, RB
Perez, EA
Mamounas, EP
Wolmark, A
Swain, SM
AF Ganz, P. A.
Land, S. R.
Geyer, C. E.
Costantino, J. P.
Pajon, E. R.
Fehrenbacher, L.
Atkins, J. N.
Polikoff, J. A.
Vogel, V. G.
Erban, J. K.
Livingston, R. B.
Perez, E. A.
Mamounas, E. P.
Wolmark, A.
Swain, S. M.
TI NSABP B-30: definitive analysis of quality of life (QOL) and menstrual
history (MH) outcomes from a randomized trial evaluating different
schedules and combinations of adjuvant therapy containing doxorubicin,
docetaxel and cyclophosphamide in women with operable, node-positive
breast cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NSABP, Pittsburgh, PA USA.
Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Colarado Canc Res Prog, Denver, CO USA.
Kaiser Permanente No Calif, Vallejo, CA USA.
SE Canc Control Consortium CCOP, Goldsboro, NC USA.
So Calif Kaiser Permanente, San Diego, CA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
ECOG, Philadelphia, PA USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Univ Arizona, Arizona Canc Ctr, Arizona Hlth Sci Ctr, Ann Arbor, MI USA.
NCCTG, Rochester, MN USA.
Mayo Clin Jacksonville, Jacksonville, FL 32224 USA.
Aultman Hlth Fdn, Canton, OH USA.
Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 81S
EP 82S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200065
ER
PT J
AU Swain, SM
Jeong, JH
Geyer, CE
Costantino, JP
Pajon, ER
Fehrenbacher, L
Atkins, JN
Polikoff, J
Vogel, VG
Erban, JK
Livingston, RB
Perez, EA
Mamounas, EP
Ganz, PA
Land, SR
Wolmark, N
AF Swain, S. M.
Jeong, J-H
Geyer, C. E.
Costantino, J. P.
Pajon, E. R.
Fehrenbacher, L.
Atkins, J. N.
Polikoff, J.
Vogel, V. G.
Erban, J. K.
Livingston, R. B.
Perez, E. A.
Mamounas, E. P.
Ganz, P. A.
Land, S. R.
Wolmark, N.
TI NSABP B-30: definitive analysis of patient outcome from a randomized
trial evaluating different schedules and combinations of adjuvant
therapy containing doxorubicin, docetaxel and cyclophosphamide in women
with operable, node-positive breast cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NSABP, Pittsburgh, PA USA.
Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
Univ Pittsburgh, NSABP Biostat Ctr, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Colorado Canc Res Prog, Denver, CO USA.
Kaiser Permanente No Calif, Vallejo, CA USA.
SE Canc Control Consortium CCOP, Goldsboro, NC USA.
So Calif Kaiser Permanente, San Diego, CA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
ECOG, Philadelphia, PA USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
SWOG, Ann Arbor, MI USA.
Univ Arizona, Arizona Canc Ctr, Arizona Hlth Sci Ctr, Tucson, AZ USA.
NCCTG, Rochester, NY USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Aultman Hlth Fdn, Canton, OH USA.
Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 81S
EP 81S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200064
ER
PT J
AU Ramaswamy, B
Bhalla, K
Cohen, B
Pellegrino, C
Hershman, D
Chuang, E
Somlo, G
Goetz, M
Swaby, R
Hopkins, U
Christos, P
Espinoza-Delgado, I
Sparano, JA
AF Ramaswamy, B.
Bhalla, K.
Cohen, B.
Pellegrino, C.
Hershman, D.
Chuang, E.
Somlo, G.
Goetz, M.
Swaby, R.
Hopkins, U.
Christos, P.
Espinoza-Delgado, I
Sparano, J. A.
TI Phase I-II study of the historic deacetylase inhibitor (HDACi)
vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer
(MBC): New York Cancer Consortium trial P7703
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Ohio State Univ, Columbus, OH 43210 USA.
Med Coll Georgia, Augusta, GA 30912 USA.
Montefiore Einstein Canc Ctr, Bronx, NY USA.
NY Presbyterian Hosp, New York, NY USA.
Weill Cornell Univ, New York, NY USA.
Mayo Clin, Rochester, MN 55905 USA.
Fox Chase Canc Ctr, Philadelphia, PA USA.
NCI, Bethesda, MD 20892 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
RI Ramaswamy, Bhuvaneswari/E-3919-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 92S
EP 93S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200097
ER
PT J
AU Harvie, M
Chapman, M
Cuzick, J
Flyvbjerg, A
Jebb, S
Mattson, M
Howell, A
AF Harvie, M.
Chapman, M.
Cuzick, J.
Flyvbjerg, A.
Jebb, S.
Mattson, M.
Howell, A.
TI The effect of intermittent versus continuous energy restriction on
biomarkers of breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 S Manchester Univ Hosp Trust, Manchester, Lancs, England.
Wolfson Inst, London, England.
Aarhus Univ, Aarhus, Denmark.
MRC Human Nutr Res Grp, Cambridge, England.
NIA, Intramural Res Program, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 95S
EP 96S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200107
ER
PT J
AU Weyandt, JD
Snyder, C
Lynch, HT
Gillanders, E
Holmes, TN
Bailey-Wilson, J
Ellsworth, RE
AF Weyandt, J. D.
Snyder, C.
Lynch, H. T.
Gillanders, E.
Holmes, T. N.
Bailey-Wilson, J.
Ellsworth, R. E.
TI Identification of BRCA1 and BRCA2 genetic modifiers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Windber Res Inst, Windber, PA USA.
Creighton Univ, Omaha, NE 68178 USA.
Natl Human Genome Inst, NIH, Baltimore, MD USA.
Henry M Jackson Fdn, Windber, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 117S
EP 118S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200173
ER
PT J
AU Hassan, S
Ferrario, C
Saragovi, U
Quenneville, L
Gaboury, L
Baccarelli, A
Salvucci, O
Basik, M
AF Hassan, S.
Ferrario, C.
Saragovi, U.
Quenneville, L.
Gaboury, L.
Baccarelli, A.
Salvucci, O.
Basik, M.
TI Combination of low plasma stromal cell-derived factor-1 and
phosphorylated-CXCR4: independent prognostic marker for breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 McGill Univ, Montreal, PQ, Canada.
Univ Montreal, Montreal, PQ, Canada.
Univ Milan, Milan, Italy.
IRCCS Maggiore Policlin Hosp, Milan, Italy.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 126S
EP 126S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200200
ER
PT J
AU Korde, LA
Mueller, CM
Nichols, K
Loud, JT
Struewing, J
Greene, MH
Mai, PL
AF Korde, L. A.
Mueller, C. M.
Nichols, K.
Loud, J. T.
Struewing, J.
Greene, M. H.
Mai, P. L.
TI Breast cancer risk in mutation-negative members of known BRCA1/2
mutation-positive families
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Natl Canc Inst, Rockville, MD USA.
Westat Corp, Rockville, MD USA.
NHGRI, Rockville, MD USA.
RI Struewing, Jeffery/I-7502-2013
OI Struewing, Jeffery/0000-0002-4848-3334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 134S
EP 134S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200224
ER
PT J
AU Muccio, DD
Lubet, RA
Atigadda, VR
Brouillette, WJ
Grubbs, CJ
AF Muccio, D. D.
Lubet, R. A.
Atigadda, V. R.
Brouillette, W. J.
Grubbs, C. J.
TI Effects of methyl derivatives of the rexinoid UAB30 on methyinitrosourea
(MNU) induced mammary cancers and on various indicators of toxicity.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Univ Alabama, Birmingham, AL USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 138S
EP 138S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200239
ER
PT J
AU Townsend, RR
Rohrs, H
Leduc, R
Yi, Y
Yao, R
Malone, JP
Edrman-Gilmore, P
Grubbs, CJ
You, M
Lubet, RA
AF Townsend, R. R.
Rohrs, H.
Leduc, R.
Yi, Y.
Yao, R.
Malone, J. P.
Edrman-Gilmore, P.
Grubbs, C. J.
You, M.
Lubet, R. A.
TI Identification of urinary biomarkers to distinguish tumor bearing and
control rats in the methylnitrosourea (MNU) - induced model of mammary
carcinogenesis: use of label-free, comparative, ultra-high resolution
nano-LC mass spectrometry.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Washington Univ, St Louis, MO USA.
Univ Alabama, Birmingham, AL USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 138S
EP 139S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200240
ER
PT J
AU Grubbs, CJ
Iwata, KK
Buck, E
Juliana, MM
Lubet, RA
AF Grubbs, C. J.
Iwata, K. K.
Buck, E.
Juliana, M. M.
Lubet, R. A.
TI Preventive effects of the EGFr inhibitor erlotinib in ER+
methyinitrosourea (MNU) induced and in ER- MMTV/Neu/P53KO mammary cancer
models.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual Meeting of the San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Univ Alabama, Birmingham, AL USA.
OSI Pharmaceut, Farmingdale, NY USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
SU S
BP 139S
EP 139S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200243
ER
PT J
AU Lu, Y
Liu, P
Wang, Y
Grubbs, C
Lubet, R
You, M
AF Lu, Y.
Liu, P.
Wang, Y.
Grubbs, C.
Lubet, R.
You, M.
TI A gene expression signature predicts cbemopreventive response of an EGFR
inhibitor in a rat mammary cancer model.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Washington Univ, St Louis, MO USA.
Washinton Univ, St Louis, MO USA.
Univ Alabama, Birmingham, AL USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 139S
EP 139S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200242
ER
PT J
AU Duchnowska, R
Jassem, J
Shen, C
Thorat, M
Li, L
Morimiya, A
Zhao, Q
Biernat, W
Mandat, T
Staszkiewicz, R
Och, W
Szostak, W
Gugala, K
Trojanowski, T
Czartoryska-Arlukowicz, B
Szczylik, C
Nakshatri, H
Steeg, P
Sledge, G
Badve, S
AF Duchnowska, R.
Jassem, J.
Shen, C.
Thorat, M.
Li, L.
Morimiya, A.
Zhao, Q.
Biernat, W.
Mandat, T.
Staszkiewicz, R.
Och, W.
Szostak, W.
Gugala, K.
Trojanowski, T.
Czartoryska-Arlukowicz, B.
Szczylik, C.
Nakshatri, H.
Steeg, P.
Sledge, G.
Badve, S.
TI Molecular characteristics of matched brain metastasis (BM) versus the
primary breast cancer (PBC).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Mil Inst Med, Warsaw, Poland.
Med Univ, Gdansk, Poland.
Indiana Univ, Indianapolis, IN 46204 USA.
Gen Hosp, Olsztyn, Poland.
Med Univ, Lublin, Poland.
Reg Canc Ctr, Bialystok, Poland.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 164S
EP 164S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200319
ER
PT J
AU Anderson, WF
Rosenberg, PS
Jatoi, I
Pfeiffer, RM
AF Anderson, W. F.
Rosenberg, P. S.
Jatoi, I
Pfeiffer, R. M.
TI The black to white breast cancer incidence rate crossover.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NCI, Bethesda, MD 20892 USA.
Natl Naval Med Ctr, Bethesda, MD USA.
RI Pfeiffer, Ruth /F-4748-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 182S
EP 182S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583200376
ER
PT J
AU Shelton, PM
Nguyen, B
Chen, A
Burger, AM
AF Shelton, P. M.
Nguyen, B.
Chen, A.
Burger, A. M.
TI Transcriptional gene expression profiles indicate response of breast
cancer cell lines to aminoflavone prodrug.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Univ Maryland, Baltimore, MD 21201 USA.
Tigris Pharmaceut Inc, Bonita Springs, FL USA.
NCI, Rockville, MD USA.
Wayne State Univ, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 201S
EP 201S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201020
ER
PT J
AU Yamaji, D
Robinson, GW
Muller, WJ
Hennighausen, L
AF Yamaji, D.
Robinson, G. W.
Muller, W. J.
Hennighausen, L.
TI Deletion of STAT5 prevents HER2/Neu/ErbB2-induced mammary tumor
development
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NIDDK, Natl Inst Hlth, Bethesda, MD USA.
McGill Univ, Montreal, PQ, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 218S
EP 218S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201073
ER
PT J
AU Stout Gergich, NL
Levy, E
Springer, B
Pfalzer, L
McGarvey, C
Gerber, L
Soballe, P
AF Stout Gergich, N. L.
Levy, E.
Springer, B.
Pfalzer, L.
McGarvey, C.
Gerber, L.
Soballe, P.
TI Pre operative assessment enables the early detection and treatment of
shoulder impairments related to breast cancer treatment.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Natl Naval Med Ctr, Bethesda, MD USA.
NIH, Bethesda, MD 20892 USA.
Walter Reed Army Med Ctr, Washington, DC 20307 USA.
Univ Michigan, Flint, MI 48503 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 277S
EP 277S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201260
ER
PT J
AU Mohebtash, M
Madan, R
Arlen, R
Jacquin, J
Mary, P
Oksook, H
Myrna, R
Jeffrey, S
James, G
AF Mohebtash, M.
Madan, R.
Arlen, R.
Jacquin, J.
Mary, P.
Oksook, H.
Myrna, R.
Jeffrey, S.
James, G.
TI Immunotherapy with MUC1/CEA vaccine alone or combined with chemotherapy
in patients with metastatic breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 [Mohebtash, M.; Madan, R.; Arlen, R.; Jacquin, J.; Mary, P.; Oksook, H.; Myrna, R.; Jeffrey, S.; James, G.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 287S
EP 288S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201290
ER
PT J
AU Gierach, GL
Loud, JT
Chow, CK
Prindiville, SA
Eng-Wong, J
Soballe, PW
Giambartolomei, C
Mai, PL
Gail, MH
Greene, MH
AF Gierach, G. L.
Loud, J. T.
Chow, C. K.
Prindiville, S. A.
Eng-Wong, J.
Soballe, P. W.
Giambartolomei, C.
Mai, P. L.
Gail, M. H.
Greene, M. H.
TI Mammographic density does not differ between unaffected BRCA1/2 mutation
carriers and women at low-to-average risk of breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NCI, Rockville, MD USA.
Natl Naval Med Ctr, Bethesda, MD USA.
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 301S
EP 301S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201329
ER
PT J
AU Glynn, SA
Boersma, BJ
Howe, TM
Ridnour, L
Wink, D
Yi, M
Yvantis, H
Ambs, S
AF Glynn, S. A.
Boersma, B. J.
Howe, T. M.
Ridnour, L.
Wink, D.
Yi, M.
Yvantis, H.
Ambs, S.
TI Aberrant inducible nitric oxide synthase expression predicts poor
survival in estrogen receptor negative breast cancer, and is associated
with a gene expression signature similar to that of basal-like breast
cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NCI, Bethesda, MD 20892 USA.
NCI, Frederick SAIC Frederick Inc, Frederick, MD 21701 USA.
Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
RI Glynn, Sharon/D-7136-2013; Boersma, Brenda/A-9270-2009
OI Glynn, Sharon/0000-0003-1459-2580; Boersma, Brenda/0000-0002-8992-2735
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 320S
EP 321S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201391
ER
PT J
AU Eng-Wong, J
Reynolds, JC
Venzon, D
Wedam, S
Prindiville, S
Zujewski, JA
Korde, L
AF Eng-Wong, J.
Reynolds, J. C.
Venzon, D.
Wedam, S.
Prindiville, S.
Zujewski, J. A.
Korde, L.
TI Effect of exemestane on bone mineral density in postmenopausal women at
increased risk for breast cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Georgetown Univ, Washington, DC USA.
NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 326S
EP 326S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201409
ER
PT J
AU Capala, J
Kramer-Marek, G
Lee, SB
Hassan, M
Kiesewetter, DO
Puri, A
Chernomordik, V
Gandjbakhche, A
Griffiths, G
Blumenthal, R
AF Capala, J.
Kramer-Marek, G.
Lee, S. B.
Hassan, M.
Kiesewetter, D. O.
Puri, A.
Chernomordik, V
Gandjbakhche, A.
Griffiths, G.
Blumenthal, R.
TI Molecular targeting of HER2 for diagnosis and therapy of breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 [Capala, J.; Kramer-Marek, G.; Lee, S. B.; Hassan, M.; Kiesewetter, D. O.; Puri, A.; Chernomordik, V; Gandjbakhche, A.; Griffiths, G.; Blumenthal, R.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 349S
EP 349S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201479
ER
PT J
AU Shoghi, KI
He, J
Su, Y
Yan, Y
Rowland, D
Garbow, J
Mach, RH
Lubet, RA
You, M
AF Shoghi, K., I
He, J.
Su, Y.
Yan, Y.
Rowland, D.
Garbow, J.
Mach, R. H.
Lubet, R. A.
You, M.
TI Multi-modality imaging of N-methyl-N-nitrosourea-induced mammary tumors
by MRI and small animal PET
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 Washington Univ, Sch Med, St Louis, MO USA.
Univ Calif Davis, Davis, CA 95616 USA.
NIH, Bethesda, MD 20892 USA.
RI Rowland, Douglas/F-3104-2014; Shoghi, Kooresh/H-7398-2014
OI Rowland, Douglas/0000-0001-8059-6905; Shoghi,
Kooresh/0000-0003-3204-457X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 350S
EP 350S
PG 1
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201483
ER
PT J
AU Glynn, SA
Boersma, BJ
Howe, TM
Ridnour, L
Wink, D
Edvardsen, H
Borresen-Dale, AL
Ambs, S
AF Glynn, S. A.
Boersma, B. J.
Howe, T. M.
Ridnour, L.
Wink, D.
Edvardsen, H.
Borresen-Dale, A-L
Ambs, S.
TI A functional SNP in the leader sequence of the manganese superoxide
dimutase gene is a predictor of breast cancer patient survival and
response to chemotherapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 31st Annual San Antonio Breast Cancer Symposium
CY DEC 10-14, 2008
CL San Antonio, TX
C1 NCI, Bethesda, MD 20892 USA.
Rikshosp Radiumhosp Med Ctr, Oslo, Norway.
RI Boersma, Brenda/A-9270-2009; Glynn, Sharon/D-7136-2013; boersma,
bendiks/O-2823-2013
OI Boersma, Brenda/0000-0002-8992-2735; Glynn, Sharon/0000-0003-1459-2580;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 366S
EP 367S
PG 2
WC Oncology
SC Oncology
GA 396HQ
UT WOS:000262583201533
ER
PT J
AU Aprelikova, O
Pandolfi, S
Tackett, S
Ferreira, M
Salnikow, K
Ward, Y
Risinger, JI
Barrett, JC
Niederhuber, J
AF Aprelikova, Olga
Pandolfi, Silvia
Tackett, Sean
Ferreira, Mark
Salnikow, Konstantin
Ward, Yvona
Risinger, John I.
Barrett, J. Carl
Niederhuber, John
TI Melanoma Antigen-11 Inhibits the Hypoxia-Inducible Factor Prolyl
Hydroxylase 2 and Activates Hypoxic Response
SO CANCER RESEARCH
LA English
DT Article
ID TRANSCRIPTIONAL ACTIVITY; PROLINE HYDROXYLATION; ANDROGEN RECEPTOR;
FACTOR HIF; PROSTATE-CANCER; HIF-1-ALPHA; EXPRESSION; OXYGEN;
FACTOR-1-ALPHA; PROTEIN
AB Activation of hypoxia-inducible factors (HIF), responsible for tumor angiogenesis and glycolytic switch, is regulated by reduced oxygen availability. Normally, HIF-alpha proteins are maintained at low levels, controlled by site-specific hydroxylation carried out by HIF prolyl hydroxylases (PHD) and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitin ligase. Using a yeast two-hybrid screen, we identified an interaction between melanoma antigen-11 (MAGE-11) cancer-testis antigen and the major HIF-a hydroxylating enzyme PHD2. The interaction was confirmed by a pull-down assay, coimmunoprecipitation, and colocalization in both normoxic and hypoxic conditions. Furthermore, MAGE-9, the closest homologue of MAGE-11, was also found to interact with PHD2. MAGE-11 inhibited PHD activity without affecting protein levels. This inhibition was accompanied by stabilization of ectopic or endogenous HIF-1 alpha protein. Knockdown of MAGE-11 by small interfering RNA results in decreased hypoxic induction of HIF-1 alpha and its target genes. Inhibition of PHD by MAGE-11, and following activation of HIFs, is a novel tumor-associated HIF regulatory mechanism. This finding provides new insights into the significance of MAGE expression in tumors and may provide valuable tools for therapeutic intervention because of the restricted expression of the MAGE gene family in cancers, but not in normal tissues. [Cancer Res 2009;69(2):616-24]
C1 [Aprelikova, Olga; Ferreira, Mark; Ward, Yvona; Niederhuber, John] NCI, Lab Tumor & Stem Cell Biol, Bethesda, MD 20892 USA.
[Aprelikova, Olga; Pandolfi, Silvia; Tackett, Sean; Risinger, John I.; Barrett, J. Carl] NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA.
[Salnikow, Konstantin] NCI, Comparat Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Risinger, John I.] Mem Hlth Univ Med Ctr, Curtis & Elizabeth Anderson Canc Inst, Savannah, GA 31404 USA.
RP Aprelikova, O (reprint author), NCI, Lab Tumor & Stem Cell Biol, Bldg 37,Room 1042,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM apreliko@mail.nih.gov
OI Tackett, Sean/0000-0001-5369-7225
FU NIH National Cancer Institute Center for Cancer Research Intramural
Research Program
FX NIH National Cancer Institute Center for Cancer Research Intramural
Research Program.
NR 45
TC 33
Z9 37
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 616
EP 624
DI 10.1158/0008-5472.CAN-08-0811
PG 9
WC Oncology
SC Oncology
GA 396HN
UT WOS:000262582900031
PM 19147576
ER
PT J
AU Yin, YZ
Yuan, HY
Zeng, X
Kopelovich, L
Glazert, RI
AF Yin, Yuzhi
Yuan, Hongyan
Zeng, Xiao
Kopelovich, Levy
Glazert, Robert I.
TI Inhibition of Peroxisome Proliferator-Activated Receptor gamma Increases
Estrogen Receptor-Dependent Tumor Specification
SO CANCER RESEARCH
LA English
DT Article
ID MAMMARY EPITHELIAL-CELLS; DMBA-INDUCED MAMMARY; BREAST-CANCER CELLS;
PPAR-GAMMA; BETA-CATENIN; STEM-CELL; MEDIATED ACTIVATION; COACTIVATOR
PGC-1; RESPONSE ELEMENTS; PROGENITOR CELLS
AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that regulates gene transcription associated with intermediary metabolism, adipocyte differentiation, and tumor suppression and proliferation. To understand the role of PPAR gamma in tumorigenesis, transgenic mice were generated with mammary gland-directed expression of the dominant-negative transgene Pax8PPAR gamma. Transgenic mice were phenotypically indistinguishable from wild-type (WT) mice, but mammary epithelial cells expressed a greater percentage of CD29(hi)/CD24(neg), CK5(+), and double-positive CK14/CK18 cells. These changes correlated with reduced PTEN and increased Ras and extracellular signal-regulated kinase (ERK) and AKT activation. Although spontaneous tumorigenesis did not occur, transgenic animals were highly susceptible to progestin/7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis, which in contrast to WT mice resulted in a high tumor multiplicity and, most importantly, in the appearance of predominantly estrogen receptor alpha-positive (ER+) ductal adenocarcinomas. Tumors expressed a similar PTENlo /pERK(hi)/pAKT(hi) phenotype as mammary epithelium and exhibited high activation of estrogen response element-dependent reporter gene activity. Tumorigenesis in MMTV-Pax8PPAR gamma mice was insensitive to the chemopreventive effect of a PPAR gamma agonist but was profoundly inhibited by the ER antagonist fulvestrant. These results reveal important new insights into the previously unrecognized role of PPAR gamma in the specification of mammary lineage and the development of ER+ tumors. [Cancer Res 2009;69(2):687-94]
C1 [Yin, Yuzhi; Yuan, Hongyan; Zeng, Xiao; Glazert, Robert I.] Georgetown Univ, Dept Oncol, Washington, DC 20007 USA.
[Yin, Yuzhi; Yuan, Hongyan; Zeng, Xiao; Glazert, Robert I.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Kopelovich, Levy] NCI, Chemoprevent Agent Dev & Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Glazert, RI (reprint author), Georgetown Univ, Dept Oncol, 3970 Reservoir Rd,NW Res Bldg,Room W318, Washington, DC 20007 USA.
EM glazerr@georgetown.edu
FU NCI NIH HHS [R01 CA111482, N01 CN043309, N01 CN43330, R01 CA11482]; NCRR
NIH HHS [C06 RR014567, C06 RR14567]
NR 62
TC 26
Z9 26
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2009
VL 69
IS 2
BP 687
EP 694
DI 10.1158/0008-5472.CAN-08-2446
PG 8
WC Oncology
SC Oncology
GA 396HN
UT WOS:000262582900040
PM 19147585
ER
PT J
AU Russo, AL
Kwon, HC
Burgan, WE
Carter, D
Beam, K
Weizheng, X
Zhang, J
Slusher, BS
Chakravarti, A
Tofilon, PJ
Camphausen, K
AF Russo, Andrea L.
Kwon, Hyuk-Chan
Burgan, William E.
Carter, Donna
Beam, Katie
Weizheng, Xu
Zhang, Jie
Slusher, Barbara S.
Chakravarti, Arnab
Tofilon, Philip J.
Camphausen, Kevin
TI In vitro and In vivo Radiosensitization of Glioblastoma Cells by the
Poly (ADP-Ribose) Polymerase Inhibitor E7016
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; 3-AMINOBENZAMIDE;
TEMOZOLOMIDE; LINES
AB Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors are undergoing clinical evaluation for cancer therapy, Because PARP inhibition has been shown to enhance tumor cell sensitivity to radiation, we investigated the in vitro and in vivo effects of the novel PARP inhibitor E7016.
Experimental Design: The effect of E7016 on the in vitro radiosensitivity of tumor cell lines was evaluated using clonogenic survival. DNA damage and repair were measured using gamma H2AX foci and neutral comet assay. Mitotic catastrophe was determined by immunostaining. Tumor growth delay was evaluated in mice for the effect of E7016 on in vivo (U251) tumor radiosensitivity.
Results: Cell lines exposed to E7016 preirradiation yielded an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1 from 1.4 to 1.7. To assess DNA double-strand breaks repair, gamma H2AX measured at 24 hours postirradiation had significantly more foci per cell in the E7016/irradiation group versus irradiation alone. Neutral comet assay further suggested unrepaired double-strand breaks with significantly greater DNA damage at 6 hours postirradiation in the combination group versus irradiation alone. Mitotic catastrophe staining revealed a significantly greater number of cells staining positive at 24 hours postirradiation in the combination group. In vivo, mice treated with E7016/irradiation/temozolomide had an additional growth delay of six days compared with the combination of temozolomide and irradiation.
Conclusions: These results indicate that E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. Moreover, enhanced growth delay with the addition of E7016 to temozolomide and radiotherapy in a glioma mouse model suggests a potential role for this drug in the treatment of glioblastoma multiforme.
C1 [Russo, Andrea L.; Kwon, Hyuk-Chan; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Burgan, William E.; Carter, Donna; Beam, Katie] NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA.
[Russo, Andrea L.] Howard Hughes Med Inst NIH Res Scholar, Bethesda, MD USA.
[Burgan, William E.; Carter, Donna; Beam, Katie] NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA.
[Weizheng, Xu; Zhang, Jie; Slusher, Barbara S.] Eisai Res Inst, Baltimore, MD USA.
[Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Tofilon, Philip J.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
FU NIH; National Cancer Institute
FX Grant support: Intramural Research Program of the NIH, National Cancer
Institute. The costs of publication of this article were defrayed in
part by the payment of page charges. This article must therefore be
hereby marked advertisement in accordance with 18 U.S. C. Section 1734
solely to indicate this fact.
NR 22
TC 97
Z9 102
U1 2
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2009
VL 15
IS 2
BP 607
EP 612
DI 10.1158/1078-0432.CCR-08-2079
PG 6
WC Oncology
SC Oncology
GA 397VD
UT WOS:000262689300023
PM 19147766
ER
PT J
AU Chung, JY
Hong, SM
Choi, BY
Cho, H
Yu, E
Hewitt, SM
AF Chung, Joon-Yong
Hong, Seung-Mo
Choi, Byeong Yeob
Cho, HyungJun
Yu, Eunsil
Hewitt, Stephen M.
TI The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic
Cholangiocarcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ADVANCED ENDOMETRIAL CARCINOMA; BILE-DUCT CARCINOMAS;
PROGNOSTIC-SIGNIFICANCE; BILIARY-TRACT; CLASSIFICATION PROBLEMS; TISSUE
MICROARRAYS; STAGING SYSTEM; PROTEIN-KINASE; CELL-LINES; CANCER
AB Purpose: The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation, and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma.
Experimental Design: Two hundred twenty-one extrahepatic cholangiocarcinoma patients with clinicopathologic data, including survival, were arrayed into tissue microarrays. Phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were studied with multiplex tissue immunoblotting assay.
Results: Expressions of p-AKTand p-mTOR were significantly increased in extrahepatic cholangiocarcinoma cases compared with normal and dysplastic bile duct epithelium (P < 0.05 both). Decreased PTEN expression was observed in patients with increasing depth of invasion (P < 0.05),T classification (P < 0.05), and stage grouping (P < 0.05), and the presence of invasion of the pancreas (P ( 0.05) and duodenum (P < 0.05). Decreased PTEN expression (P = 0.004) as well as decreased PTEN/p-AKT (P = 0.003) and PTEN/p-mTOR (P = 0.009) expression showed shorter survival by univariate but not by multivariate analysis.
Conclusions: The AKT pathway is activated in a subset of extrahepatic cholangiocarcinoma. Elevated PTEN expression correlates with longer survival. Quantitative data obtained by multiplex tissue immunoblotting may provide additional information than assessment of immunohistochemistry alone. Quantitative analysis of PTEN, PTEN/p-AKT and PTEN/p-mTOR shows differences in survival by univariate analysis.
C1 [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Hong, Seung-Mo] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Choi, Byeong Yeob; Cho, HyungJun] Korea Univ, Dept Stat, Seoul, South Korea.
[Yu, Eunsil] Univ Ulsan, Dept Pathol, Asan Med Ctr, Seoul, South Korea.
RP Hewitt, SM (reprint author), Adv Technol Ctr, TARP Lab, MSC 4605, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Hong, Seung-Mo/0000-0002-8888-6007;
Chung, Joon-Yong/0000-0001-5041-5982
FU NIH; National Cancer Institute; Center for Cancer Research; Korean
Government [KRF-2007-331-C00065]
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, and in part by the Korea Research Foundation
Grant funded by the Korean Government (MOEHRD, Basic Research Promotion
Fund; KRF-2007-331-C00065).
NR 39
TC 53
Z9 59
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2009
VL 15
IS 2
BP 660
EP 667
DI 10.1158/1078-0432.CCR-08-1084
PG 8
WC Oncology
SC Oncology
GA 397VD
UT WOS:000262689300029
PM 19147772
ER
PT J
AU Ghosh, P
Albert, PS
AF Ghosh, Pulak
Albert, Paul S.
TI A Bayesian analysis for longitudinal semicontinuous data with an
application to an acupuncture clinical trial
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
ID PROFILING PROVIDERS; HEALTH-CARE; MODEL
AB In many biomedical applications, researchers encounter semicontinuous data where data are either continuous or zero. When the data are collected over time the observations may be correlated. Analysis of this kind of longitudinal semicontinuous data is challenging due to the presence of strong skewness in the data. A flexible class of zero-inflated models in a longitudinal setting is developed. A Bayesian approach is used to analyze longitudinal data from an acupuncture clinical trial, in which the effects of active acupuncture,sham acupuncture and standard medical care is compared on chemotherapy-induced nausea inpatients who were treated for advanced breast cancer. A spline model is introduced into the linear predictor of the model to explore the possibility of a nonlinear treatment effect. Possible serial correlation between successive observations is also accounted using the Brownian motion. Thus, the approach taken in this paper provides for a more flexible modeling framework and, with the use of WinBUGS, provides for a computationally simpler approach than direct maximum-likelihood. The Bayesian methodology is illustrated with the acupuncture clinical trial data. (C) 2008 Elsevier B.V. All rights reserved..
C1 [Ghosh, Pulak] Emory Univ, Dept Biostat, Atlanta, GA 30322 USA.
[Ghosh, Pulak] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Ghosh, P (reprint author), Emory Univ, Dept Biostat, Atlanta, GA 30322 USA.
EM pulakghosh@gmail.com
FU Intramural NIH HHS [Z99 HD999999]
NR 28
TC 15
Z9 16
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
EI 1872-7352
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD JAN 15
PY 2009
VL 53
IS 3
BP 699
EP 706
DI 10.1016/j.csda.2008.09.011
PG 8
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 414AU
UT WOS:000263837100012
PM 19763231
ER
PT J
AU Matsuda, M
Chitnis, AB
AF Matsuda, Miho
Chitnis, Ajay B.
TI Interaction with Notch determines endocytosis of specific Delta ligands
in zebrafish neural tissue
SO DEVELOPMENT
LA English
DT Article
DE Notch signaling; Endocytosis; DeltaD; DeltaA; DeltaC; Neurogenesis;
Zebrafish; Lateral inhibition; Cis inhibition
ID NEUROGENIC GENE-DELTA; MIND BOMB; LATERAL INHIBITION; UBIQUITIN LIGASES;
DSL PROTEINS; DROSOPHILA; EXPRESSION; HOMOLOG; ACTIVATION; HINDBRAIN
AB Mind bomb1 (Mib1)-mediated endocytosis of the Notch ligand DeltaD is essential for activation of Notch in a neighboring cell. Although most DeltaD is localized in cytoplasmic puncta in zebrafish neural tissue, it is on the plasma membrane in mib1 mutants because Mib1-mediated endocytosis determines the normal subcellular localization of DeltaD. Knockdown of Notch increases cell surface DeltaA and DeltaD, but not DeltaC, suggesting that, like Mib1, Notch regulates endocytosis of specific ligands. Transplant experiments show that the interaction with Notch, both in the same cell (in cis) and in neighboring cells (in trans), regulates DeltaD endocytosis. Whereas DeltaD endocytosis following interaction in trans activates Notch in a neighboring cell, endocytosis of DeltaD and Notch following an interaction in cis is likely to inhibit Notch signaling by making both unavailable at the cell surface. The transplantation experiments reveal a heterogeneous population of progenitors: in some, cis interactions are more important; in others, trans interactions are more important; and in others, both cis and trans interactions are likely to contribute to DeltaD endocytosis. We suggest that this heterogeneity represents the process by which effective lateral inhibition leads to diversification of progenitors into cells that become specialized to deliver or receive Delta signals, where trans and cis interactions with Notch play differential roles in DeltaD endocytosis.
C1 [Matsuda, Miho; Chitnis, Ajay B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neural Dev Dynam, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
RP Chitnis, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neural Dev Dynam, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
EM chitnisa@mail.nih.gov
RI Matsuda, Miho/G-1616-2011
FU Intramural Research Program of the NIH/ NICHD; JSPS research fellowship
FX We thank Julian Lewis ( Cancer Research UK, London) for providing zdC1
and zdD2 antibodies; Motoyuki Itoh ( Nagoya University, Japan) for
valuable discussions and preliminary exploration of these questions; and
all the members of Chitnis laboratory for their comments. This work was
supported by the Intramural Research Program of the NIH/ NICHD. This
work was also supported by a JSPS research fellowship ( M. M.).
Deposited in PMC for release after 12 months.
NR 41
TC 40
Z9 40
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 0950-1991
J9 DEVELOPMENT
JI Development
PD JAN 15
PY 2009
VL 136
IS 2
BP 197
EP 206
DI 10.1242/dev.027938
PG 10
WC Developmental Biology
SC Developmental Biology
GA 387BU
UT WOS:000261927500004
PM 19056830
ER
PT J
AU Ishibe, S
Karihaloo, A
Ma, H
Zhang, J
Marlier, A
Mitobe, M
Togawa, A
Schmitt, R
Czyczk, J
Kashgarian, M
Geller, DS
Thorgeirsson, SS
Cantley, LG
AF Ishibe, Shuta
Karihaloo, Anil
Ma, Hong
Zhang, Junhui
Marlier, Arnaud
Mitobe, Mitchihiro
Togawa, Akashi
Schmitt, Roland
Czyczk, Jan
Kashgarian, Michael
Geller, David S.
Thorgeirsson, Snorri S.
Cantley, Lloyd G.
TI Met and the epidermal growth factor receptor act cooperatively to
regulate final nephron number and maintain collecting duct morphology
SO DEVELOPMENT
LA English
DT Article
DE Kidney; Met receptor; Ureteric bud; Branching; Mouse
ID URETERAL BUD; KIDNEY DEVELOPMENT; EPITHELIAL MORPHOGENESIS; EGF
RECEPTOR; BRANCHING MORPHOGENESIS; FACTOR/SCATTER FACTOR; TYROSINE
KINASE; C-MET; HEPATOCYTE; MICE
AB Ureteric bud (UB) branching during kidney development determines the final number of nephrons. Although hepatocyte growth factor and its receptor Met have been shown to stimulate branching morphogenesis in explanted embryonic kidneys, loss of Met expression is lethal during early embryogenesis without obvious kidney abnormalities. Met(fl/fl);HoxB7-Cre mice, which lack Met expression selectively in the UB, were generated and found to have a reduction in final nephron number. These mice have increased Egf receptor expression in both the embryonic and adult kidney, and exogenous Egf can partially rescue the branching defect seen in kidney explants. Met(fl/fl); HoxB7-Cre; wa-2/wa-2 mice, which lack normal Egfr and Met signaling, exhibit small kidneys with a marked decrease in UB branching at E14.5 as well as a reduction in final glomerular number. These mice developed progressive interstitial fibrosis surrounding collecting ducts with kidney failure and death by 3-4 weeks of age. Thus, in support of previous in vitro findings, Met and the Egf receptor can act cooperatively to regulate UB branching and mediate maintenance of the normal adult collecting duct.
C1 [Ishibe, Shuta; Karihaloo, Anil; Ma, Hong; Zhang, Junhui; Marlier, Arnaud; Mitobe, Mitchihiro; Togawa, Akashi; Geller, David S.; Cantley, Lloyd G.] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT 06510 USA.
[Czyczk, Jan; Kashgarian, Michael] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schmitt, Roland] Hannover Med Sch, Dept Nephrol, D-3000 Hannover, Germany.
RP Ishibe, S (reprint author), Yale Univ, Sch Med, Nephrol Sect, New Haven, CT 06510 USA.
EM shuta.ishibe@yale.edu; lloyd.cantley@yale.edu
FU R01; American Heart Association; [DK65109]
FX This work was supported by an R01 award to L. G. C. (DK65109) and an
American Heart Association Fellow-to-Faculty and American Society of
Nephrology Gottschalk award to S. I. Deposited in PMC for release after
12 months.
NR 55
TC 57
Z9 57
U1 0
U2 0
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JAN 15
PY 2009
VL 136
IS 2
BP 337
EP 345
DI 10.1242/dev.024463
PG 9
WC Developmental Biology
SC Developmental Biology
GA 387BU
UT WOS:000261927500017
PM 19103805
ER
PT J
AU Bras, J
Simon-Sanchez, J
Federoff, M
Morgadinho, A
Januario, C
Ribeiro, M
Cunha, L
Oliveira, C
Singleton, AB
AF Bras, Jose
Simon-Sanchez, Javier
Federoff, Monica
Morgadinho, Ana
Januario, Cristina
Ribeiro, Maria
Cunha, Luis
Oliveira, Catarina
Singleton, Andrew B.
TI Lack of replication of association between GIGYF2 variants and Parkinson
disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID WHOLE-GENOME ASSOCIATION; MUTATIONS; GENE; FAMILIES; LINKAGE; OMI/HTRA2;
SAMPLE; PARK11
AB Mutations in GIGYF2 have recently been described as causative of Parkinson's disease in Europeans. In an attempt to replicate these results in independent populations, we sequenced the entire coding region of GIGYF2 in a large series of Portuguese and North American samples. We report the finding of two of the previously published mutations in neurologically normal Control individuals. This suggests that mutations in GIGYF2 are not strongly related to the development of the disease in either of these populations.
C1 [Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Bras, Jose; Oliveira, Catarina] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal.
[Simon-Sanchez, Javier] CSIC, Inst Biomed Valencia, Dept Genom & Prote, Unidad Genet Mol, Valencia 46010, Spain.
[Morgadinho, Ana; Januario, Cristina; Ribeiro, Maria; Cunha, Luis; Oliveira, Catarina] Coimbra Univ Hosp, Neurol Serv, P-3000 Coimbra, Portugal.
[Singleton, Andrew B.] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, Intramural Res Program, NIH, Room 1A1014,Bldg 35,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Bras,
Jose/A-1428-2011; Singleton, Andrew/C-3010-2009;
OI Oliveira, Catarina/0000-0001-6942-4328
FU National Institute on Aging; National Institutes of Health; Department
of Health and Human Services [Z01-AG000957-05]; Fundacao para a Ciencia
e Tecnologia [SFRH/BD/29647/2006]
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, Annual Report number Z01-AG000957-05 and
Fundacao para a Ciencia e Tecnologia grant (SFRH/BD/29647/2006).
NR 20
TC 35
Z9 38
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 JAN 15
PY 2009
VL 18
IS 2
BP 341
EP 346
DI 10.1093/hmg/ddn340
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 386QK
UT WOS:000261897500012
PM 18923002
ER
PT J
AU Fitzgerald, PJ
AF Fitzgerald, Paul J.
TI Is norepinephrine an etiological factor in some types of cancer?
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Review
DE norepinerthrine; pharmacology; clonidine; adrenoceptor; rodent;
hypertension; epidemiology; pheochromocytoma
ID NITRO-N-NITROSOGUANIDINE; BETA-ADRENERGIC RECEPTORS; LOW-PROTEIN DIET;
WISTAR RATS; GASTRIC CARCINOGENESIS; BREAST-CANCER; PROSTATE-CANCER;
COLON CARCINOGENESIS; TRICYCLIC ANTIDEPRESSANTS; CELL-LINES
AB I examine evidence that the signaling molecule norepinephrine (NE) is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence: (i) rodent studies of tumorigenesis in the context or NE manipulation; (ii) human studies or tricyclic antidepressant use and cancer rate; (iii) existence of pheochromocytoma, a cancer of the adrenal glands; (iv) cancer rate in families with individuals who have bipolar disorder; (v) hypertension and cancer risk; (vi) excessive body weight and cancer risk; and (vii) psychological stressors and cancer risk. Three aspects or the body's NE system are consistent with it playing an etiological role in various types of cancer: (i) NE circulates in the blood and can thereby access organ systems throughout the body, in addition to direct peripheral release by the sympathetic nervous system and being released within the brain; i I many of the hotly's organs possess NE receptors oil the outer surface of at least some or their cells; (iii) by binding to its extracellular receptors, NE affects intracellular second messenger systems that could influence carcinogenesis. Most importantly, use of existing pharmaceutical drugs that either lower the level of NE (such as clonidine) or block NE receptors may lower the probability of an individual developing cancer, and this hypothesis could be tested iminediately fly all epidemiologist through examination or existing medical records. (C) 2008 Wiley-Liss, life.
C1 [Fitzgerald, Paul J.] Johns Hopkins Univ, Krieger Mind Brain Inst, Baltimore, MD 21218 USA.
RP Fitzgerald, PJ (reprint author), NIAAA, 5625 Fishers Lane,Room TS20, Bethesda, MD 20852 USA.
EM pfitz@mbi.mb.jhu.edu
NR 82
TC 36
Z9 38
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JAN 15
PY 2009
VL 124
IS 2
BP 257
EP 263
DI 10.1002/ijc.24063
PG 7
WC Oncology
SC Oncology
GA 388HJ
UT WOS:000262010600001
PM 19004004
ER
PT J
AU Negri, E
Boffetta, P
Berthiller, J
Castellsague, X
Curado, MP
Dal Maso, L
Daudt, AW
Fabianova, E
Fernandez, L
Wunsch, V
Franceschi, S
Hayes, RB
Herrero, R
Koifman, S
Lazarus, P
Lence, JJ
Levi, F
Mates, D
Matos, E
Menezes, A
Muscat, J
Eluf-Neto, J
Olshan, AF
Rudnai, P
Shangina, O
Sturgis, EM
Szeszenia-Dabrowska, N
Talamini, R
Wei, Q
Winn, DM
Zaridze, D
Lissowska, J
Zhang, ZF
Ferro, G
Brennan, P
La Vecchia, C
Hashibe, M
AF Negri, Eva
Boffetta, Paolo
Berthiller, Julien
Castellsague, Xavier
Curado, Maria Paula
Dal Maso, Luigino
Daudt, Alexander W.
Fabianova, Eleonora
Fernandez, Leticia
Wunsch-Filho, Victor
Franceschi, Silvia
Hayes, Richard B.
Herrero, Rolando
Koifman, Sergio
Lazarus, Philip
Lence, Juan J.
Levi, Fabio
Mates, Dana
Matos, Elena
Menezes, Ana
Muscat, Joshua
Eluf-Neto, Jose
Olshan, Andrew F.
Rudnai, Peter
Shangina, Oxana
Sturgis, Erich M.
Szeszenia-Dabrowska, Neonilia
Talamini, Renato
Wei, Qingyi
Winn, Deborah M.
Zaridze, David
Lissowska, Jolanta
Zhang, Zuo-Feng
Ferro, Gilles
Brennan, Paul
La Vecchia, Carlo
Hashibe, Mia
TI Family history of cancer: Pooled analysis in the International Head and
Neck Cancer Epidemiology consortium
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE head and neck cancer; family history; pooled analysis; tobacco; alcohol
ID SQUAMOUS-CELL CARCINOMA; UPPER AERODIGESTIVE TRACT; ORAL-CANCER;
PHARYNGEAL CANCER; PUERTO-RICO; RISK; SMOKING; ALCOHOL; TOBACCO;
DRINKING
AB Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR = 1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR = 2.2, 95% CI 1.6-3.1) rather than a parent (OR = 1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR = 1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR = 1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR = 1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC. (C) 2008 Wiley-Liss, Inc,
C1 [Hashibe, Mia] Int Agcy Res Canc, Lifestyle Environm & Canc Grp, F-69008 Lyon, France.
[Negri, Eva; La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy.
[Castellsague, Xavier] Inst Catala Oncol, Barcelona, Spain.
[Dal Maso, Luigino; Talamini, Renato] Aviano Canc Ctr, Dept Epidemiol, I-33081 Aviano, Italy.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Fabianova, Eleonora] Specialized State Hlth Inst, Banska Bystrica, Slovakia.
[Fernandez, Leticia; Wunsch-Filho, Victor; Lence, Juan J.] Natl Inst Oncol & Radiobiol, Havana, Cuba.
[Hayes, Richard B.; Winn, Deborah M.] Natl Canc Inst, Bethesda, MD USA.
[Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Lazarus, Philip; Muscat, Joshua] Penn State Coll Med, Hershey, PA USA.
[Levi, Fabio] Univ Lausanne, Inst Social & Prevent Med, Lausanne, Switzerland.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Eluf-Neto, Jose] Univ Sao Paulo, Sao Paulo, Brazil.
[Olshan, Andrew F.] UNC, Sch Publ Hlth, Chapel Hill, NC USA.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Shangina, Oxana; Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
[Sturgis, Erich M.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Lodz, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[La Vecchia, Carlo] Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy.
RP Hashibe, M (reprint author), Int Agcy Res Canc, Lifestyle Environm & Canc Grp, 150 Cours Albert Thomas, F-69008 Lyon, France.
EM hashibe@iarc.fr
RI Wunsch Filho, Victor/C-4475-2012; Negri, Eva/B-7244-2013; Inca,
Inct/K-2204-2013; Zaridze, David/K-5605-2013; Epidemiologicas, Centro de
pesquisas /D-4561-2013; Eluf-Neto, Jose/B-2522-2009; Menezes,
Ana/G-7266-2012; Szeszenia-Dabrowska, Neonila/F-7190-2010; Castellsague
Pique, Xavier/N-5795-2014; Curado, Maria Paula/M-6200-2013;
OI Negri, Eva/0000-0001-9712-8526; Eluf-Neto, Jose/0000-0001-7504-2115;
Castellsague Pique, Xavier/0000-0002-0802-3595; Curado, Maria
Paula/0000-0001-8172-2483; mates, dana/0000-0002-6219-9807; Lissowska,
Jolanta/0000-0003-2695-5799; dal maso, luigino/0000-0001-6163-200X; La
Vecchia, Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute; US National Institutes of Health [R03
CA113157]
FX Grant sponsor: National Cancer Institute, US National Institutes of
Health: Grant number: R03 CA113157.
NR 41
TC 58
Z9 59
U1 0
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JAN 15
PY 2009
VL 124
IS 2
BP 394
EP 401
DI 10.1002/ijc.23848
PG 8
WC Oncology
SC Oncology
GA 388HJ
UT WOS:000262010600019
PM 18814262
ER
PT J
AU Kamangar, F
Diaw, L
Wei, WQ
Abnet, CC
Wang, GQ
Roth, MJ
Liu, B
Lu, N
Giffen, C
Qiao, YL
Dawsey, SM
AF Kamangar, Farin
Diaw, Lena
Wei, Wen-Qiang
Abnet, Christian C.
Wang, Guo-Qing
Roth, Mark. J.
Liu, Bing
Lu, Ning
Giffen, Carol
Qiao, You-Lin
Dawsey, Sanford M.
TI Serum pepsinogens and risk of esophageal squamous dysplasia
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE esophageal cancer; squamous dysplasia; pepsinogen; China
ID HELICOBACTER-PYLORI INFECTION; CHRONIC ATROPHIC GASTRITIS; CELL
CARCINOMA; PERNICIOUS-ANEMIA; CANCER; CHINA; POPULATION; LINXIAN;
ADENOCARCINOMA; HISTOLOGY
AB Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC. We measured serum PGI and PGII, using enzyme-linked immunosorbent assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles) or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08-4.18), comparing the lowest versus the highest quartile. The association between the lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03. Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC. Published 2008 Wiley-Liss, Inc. This article is a US Government work and, as such. is in the public domain in the United States of America.
C1 [Kamangar, Farin; Abnet, Christian C.; Roth, Mark. J.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Diaw, Lena] NCI, Adv Technol Ctr, Bethesda, MD 20892 USA.
[Wei, Wen-Qiang; Wang, Guo-Qing; Liu, Bing; Lu, Ning; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China.
[Giffen, Carol] Informat Management Serv Inc, Bethesda, MD USA.
RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 3034, Bethesda, MD 20892 USA.
EM kamangaf@mail.nih.gov
RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843
FU National Cancer Institute; NIH [N01-RC-47702]
FX Grant sponsor: Intramural Research Program, National Cancer Institute:
Grant sponsor: NIH; Grant number: N01-RC-47702.
NR 31
TC 21
Z9 21
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JAN 15
PY 2009
VL 124
IS 2
BP 456
EP 460
DI 10.1002/ijc.23918
PG 5
WC Oncology
SC Oncology
GA 388HJ
UT WOS:000262010600028
PM 18844222
ER
PT J
AU De Lay, N
Gottesman, S
AF De Lay, Nicholas
Gottesman, Susan
TI The Crp-Activated Small Noncoding Regulatory RNA CyaR (RyeE) Links
Nutritional Status to Group Behavior
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID OUTER-MEMBRANE PROTEINS; CAMP RECEPTOR PROTEIN; CATABOLITE REPRESSION
CONTROL; ENVELOPE STRESS-RESPONSE; ESCHERICHIA-COLI;
PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; CARBON METABOLISM;
GLOBAL REGULATOR; DOWN-REGULATION
AB Small noncoding regulatory RNAs (sRNAs) play a key role in regulating the expression of many genes in Escherichia coli and other bacteria. Many of the sRNAs identified in E. coli bind to mRNAs in an Hfq-dependent manner and stimulate or inhibit translation of the mRNAs. Several sRNAs are regulated by well-studied global regulators. Here, we report characterization of the CyaR (RyeE) sRNA, which was previously identified in a global search for sRNAs in E. coli. We demonstrated that CyaR is positively regulated by the global regulator Crp under conditions in which cyclic AMP levels are high. We showed by using microarray analysis and Northern blotting that several genes are negatively regulated by CyaR, including ompX, encoding a major outer membrane protein; luxS, encoding the autoinducer-2 synthase; nadE, encoding an essential NAD synthetase; and yqaE, encoding a predicted membrane protein with an unknown function. Using translational lacZ fusions to yqaE, ompX, nadE, and luxS, we demonstrated that the negative regulation of these genes by CyaR occurs at the posttranscriptional level and is direct. Different portions of a highly conserved 3' region of CyaR are predicted to pair with sequences near the ribosome binding site of each of these targets; mutations in this sequence affected regulation, and compensatory mutations in the target mRNA restored regulation, confirming that there is direct regulation by the sRNA. These results provide insight into the mechanisms by which Crp negatively regulates genes such as luxS and ompX and provide a link between catabolite repression, quorum sensing, and nitrogen assimilation in E. coli.
C1 [De Lay, Nicholas; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 5132, Bethesda, MD 20892 USA.
EM susang@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.
NR 72
TC 90
Z9 91
U1 1
U2 6
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 JAN 15
PY 2009
VL 191
IS 2
BP 461
EP 476
DI 10.1128/JB.01157-08
PG 16
WC Microbiology
SC Microbiology
GA 389TP
UT WOS:000262117700002
PM 18978044
ER
PT J
AU Domenech, P
Kobayashi, H
LeVier, K
Walker, GC
Barry, CE
AF Domenech, Pilar
Kobayashi, Hajime
LeVier, Kristin
Walker, Graham C.
Barry, Clifton E., III
TI BacA, an ABC Transporter Involved in Maintenance of Chronic Murine
Infections with Mycobacterium tuberculosis
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI SBMA; SINORHIZOBIUM-MELILOTI; LIPID-A; ANTIMICROBIAL
ACTIVITY; LEGUME SYMBIOSIS; GENETIC-ANALYSIS; MUTAGENESIS; RESISTANCE;
PROTEIN; IDENTIFICATION
AB BacA is an inner membrane protein associated with maintenance of chronic infections in several diverse host-pathogen interactions. To understand the function of the bacA gene in Mycobacterium tuberculosis (Rv1819c), we insertionally inactivated this gene and analyzed the resulting mutant for a variety of phenotypes. BacA deficiency in M. tuberculosis did not affect sensitivity to detergents, acidic pH, and zinc, indicating that there was no global compromise in membrane integrity, and a comprehensive evaluation of the major lipid constituents of the cell envelope failed to reveal any significant differences. Infection of mice with this mutant revealed no impact on establishment of infection but a profound effect on maintenance of extended chronic infection and ultimate outcome. As in alphaproteobacteria, deletion of BacA in M. tuberculosis led to increased bleomycin resistance, and heterologous expression of the M. tuberculosis BacA homolog in Escherichia coli conferred sensitivity to antimicrobial peptides. These results suggest a striking conservation of function for BacA-related proteins in transport of a critical molecule that determines the outcome of the host-pathogen interaction.
C1 [Domenech, Pilar; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Kobayashi, Hajime; LeVier, Kristin; Walker, Graham C.] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, Bldg 33,Room 2W20D,33 North Dr, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012;
OI /0000-0001-7243-8261
FU NIH, NIAID; National Institutes of Health [GM31010]
FX This research was supported by the Intramural Research Programs of the
NIH, NIAID. This work was also supported by National Institutes of
Health grant GM31010 to G. C. W. G. C. W. is an American Cancer Society
Research Professor.
NR 45
TC 37
Z9 42
U1 0
U2 7
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 JAN 15
PY 2009
VL 191
IS 2
BP 477
EP 485
DI 10.1128/JB.01132-08
PG 9
WC Microbiology
SC Microbiology
GA 389TP
UT WOS:000262117700003
PM 18996991
ER
PT J
AU Ichikawa, N
Iwabuchi, K
Kurihara, H
Ishii, K
Kobayashi, T
Sasaki, T
Hattori, N
Mizuno, Y
Hozumi, K
Yamada, Y
Arikawa-Hirasawa, E
AF Ichikawa, Naoki
Iwabuchi, Kazuhisa
Kurihara, Hidetake
Ishii, Kumiko
Kobayashi, Toshihide
Sasaki, Takako
Hattori, Nobutaka
Mizuno, Yoshikuni
Hozumi, Kentaro
Yamada, Yoshihiko
Arikawa-Hirasawa, Eri
TI Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is
crucial for neurite outgrowth
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE GM1; Integrin; Laminin; Lipid rafts; Neurite outgrowth
ID NERVE GROWTH-FACTOR; EXTRACELLULAR-MATRIX MOLECULES; MELANOMA B16 CELLS;
PC12 CELLS; ALPHA-1 CHAIN; G-DOMAIN; GLYCOSIGNALING DOMAIN; NEURONAL
DEVELOPMENT; INTEGRIN ACTIVATION; HIPPOCAMPAL-NEURONS
AB Laminin-1, an extracellular matrix molecule, promotes neurite outgrowth through the interaction of integrin and actin. Monosialoganglioside GM1 in the lipid rafts associates with and activates the NGF receptor TrkA, and enhances neurite outgrowth. However, the role of GM1 in laminin-1-induced neurite outgrowth was still unclear. Here, we describe that laminin-1 binds to GM1 through a carbohydrate moiety and a specific conformation of GM1, induces focal formation of large clusters of GM1, and enhances the relocation of TrkA in the membrane of dorsal root ganglion (DRG) and PC12 cells. We found that laminin-1-mediated clustering of GM1 causes the translocation and enrichment of beta 1 integrin in lipid rafts where TrkA colocalizes with beta 1 integrin - and the activation of Lyn, Akt and MAPK to promote the outgrowth of neurites. Our results suggest that the binding of laminin-1 to GM1 facilitates the formation of a focal microdomain in the membrane, and enhances signal transduction that promotes neurite outgrowth by linking NGF-TrkA signaling with the laminin-integrin signaling pathways.
C1 [Ichikawa, Naoki; Mizuno, Yoshikuni; Arikawa-Hirasawa, Eri] Juntendo Univ, Sch Med, Res Inst Dis Old Age, Tokyo 113, Japan.
[Ichikawa, Naoki; Hattori, Nobutaka; Mizuno, Yoshikuni; Arikawa-Hirasawa, Eri] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan.
[Iwabuchi, Kazuhisa] Juntendo Univ, Sch Med, Inst Environm & Gender Specif Med, Tokyo 113, Japan.
[Kurihara, Hidetake] Juntendo Univ, Sch Med, Dept Anat, Tokyo 113, Japan.
[Ishii, Kumiko; Kobayashi, Toshihide] RIKEN Frontier Res Syst, Sphingolipid Funct Lab, Saitama, Japan.
[Sasaki, Takako] Shriners Hosp Children, Res Ctr, Portland, OR 97201 USA.
[Hozumi, Kentaro; Yamada, Yoshihiko] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Sch Med, Res Inst Dis Old Age, Tokyo 113, Japan.
EM ehirasaw@med.juntendo.ac.jp
RI Kobayashi, Toshihide/B-6298-2015
OI Kobayashi, Toshihide/0000-0002-4811-7270
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
[17082008]; National Institutes of Health, National Institute of Dental
and Craniofacial Research, USA
FX We thank Hynda Kleinman and Alessandro Prinetti for their valuable
suggestions. This work was supported in part by a High Technology
Research Center Grant and Grants-in-Aid 17082008 from the Ministry of
Education, Culture, Sports, Science and Technology of Japan (E.A.-H.)
and the Intramural Research Program of the National Institutes of
Health, National Institute of Dental and Craniofacial Research, USA
(Y.Y.).
NR 72
TC 48
Z9 49
U1 0
U2 3
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 JAN 15
PY 2009
VL 122
IS 2
BP 289
EP 299
DI 10.1242/jcs.030338
PG 11
WC Cell Biology
SC Cell Biology
GA 390AU
UT WOS:000262137500016
PM 19118221
ER
PT J
AU Danish, M
Gardner, ER
Chen, XH
Figg, WD
AF Danish, Matthew
Gardner, Erin R.
Chen, Xiaohong
Figg, William D.
TI Determination of a benzamide histone deacetylase inhibitor, MS-275, in
human plasma by liquid chromatography with mass-spectrometric detection
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Histone deacetylase inhibitor; LC/MS; MS-275; Benzanilide
AB An analytical method was developed and validated for the quantitative determination of the histone deacetylase inhibitor MS-275 in human plasma. Calibration curves were linear in the concentration range of 1-250 ng/mL. Sample pretreatment involved a liquid-liquid extraction of 0.1 mL aliquots of plasma with methyl tert-butyl ether. MS-275 and the internal standard, benzanilide, were separated on a Zorbax SB-Phenyl column (4.6mrn x 75 mm I.D., 3.5 mu m), using a mobile phase composed of methanol and 10 mM ammonium formate (pH 2.9). The column eluent was monitored by mass spectrometry with electrospray ionization. Accuracy and precision of three concentrations of quality control samples ranged from 96.56 to 107.02% and 0.97 to 4.29%, respectively. This method represents an improvement over the previously published analytical assay for this agent, increasing the accuracy and precision (through addition of a suitable internal standard) and expanding the analytical range. The developed method was applied to study the pharmacokinetics of MS-275 in 724 clinical samples. Published by Elsevier B.V.
C1 [Danish, Matthew; Chen, Xiaohong; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute; National Institutes of Health [NOI-CO-12400]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 6
TC 3
Z9 3
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD JAN 15
PY 2009
VL 877
IS 3
BP 355
EP 359
DI 10.1016/j.jchromb.2008.12.018
PG 5
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 400OJ
UT WOS:000262877500038
PM 19117815
ER
PT J
AU Xu, M
Sharma, A
Wiest, DL
Sen, JM
AF Xu, Mai
Sharma, Archna
Wiest, David L.
Sen, Jyoti Misra
TI Pre-TCR-Induced beta-Catenin Facilitates Traversal through
beta-Selection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL-RECEPTOR; GLYCOGEN-SYNTHASE KINASE-3; WNT SIGNALING PATHWAY;
THYMOCYTES IN-VIVO; POSITIVE SELECTION; TRANSCRIPTIONAL ACTIVATION;
GAMMA-CATENIN; HMG-BOX; EXPRESSION; GENE
AB Pre-TCR induced signals regulate development of the alpha beta TCR lineage cells at the beta-selection checkpoint. We have previously shown that conditional deletion of beta-catenin, a central mediator of Wnt-beta-catenin-T cell factor signaling pathway, impairs traversal through the beta-selection checkpoint. We now provide a molecular basis for the impairment. We demonstrate that pre-TCR signals specifically stabilize beta-catenin in CD4(-)CD8(-) double negative thymocytes during beta-selection. Pre-TCR induced Erk activity was required to stabilize beta-catenin. Enforced expression of stabilized beta-catenin was sufficient to mediate aspects of beta-selection including sustained expression of early growth response (Egr) genes. Consistently, deletion of beta-catenin reduced induction of Egr gene expression by the pre-TCR signal and blocked efficient beta-selection. Thus, we demonstrate that pre-TCR induced beta-catenin sustains expression of Egr genes that facilitate traversal through the beta-selection checkpoint. The Journal of Immunology, 2009, 182: 751-758.
C1 [Sen, Jyoti Misra] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wiest, David L.] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA.
RP Sen, JM (reprint author), NIA, Lymphocyte Dev Unit, Immunol Lab, NIH,Biomed Res Ctr, 08C218,251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM Jyoti-Sen@nih.gov
RI Sharma, Archna/R-9377-2016;
OI Sharma, Archna/0000-0003-4745-0220; Wiest, David/0000-0002-0792-3188
FU National Institute on Aging at the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging at the National Institutes of Health.
NR 59
TC 20
Z9 20
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 JAN 15
PY 2009
VL 182
IS 2
BP 751
EP 758
PG 8
WC Immunology
SC Immunology
GA 393RO
UT WOS:000262390600003
PM 19124717
ER
PT J
AU Xu, M
Sharma, A
Hossain, MZ
Wiest, DL
Sen, JM
AF Xu, Mai
Sharma, Archna
Hossain, M. Zulfiquer
Wiest, David L.
Sen, Jyoti Misra
TI Sustained Expression of Pre-TCR Induced beta-Catenin in
Post-beta-Selection Thymocytes Blocks T Cell Development
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ROR-GAMMA-T; TRANSCRIPTION FACTORS; POSITIVE SELECTION; IN-VIVO;
TRANSGENIC MICE; RECEPTOR; SIGNALS; DIFFERENTIATION; SURVIVAL; CHAIN
AB Pre-TCR and IL-7R signals regulate beta-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that beta-catenin in cooperation with TCF regulates beta-selection. In this paper, we demonstrate that beta-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-beta-selection thymocytes. Pre-TCR-induced beta-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express ROR gamma t, which is essential for maturation to the CD4(+)CD8(+) double positive (DP) stage. Sustained expression of beta-catenin results in the generation of IL-7R-, Egr-, and TGF beta-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-beta-selection, pre-TCR-induced beta-catenin expression must return to background levels for efficient transition to the DP stage. The Journal of Immunology, 2009, 182: 759-765.
C1 [Sen, Jyoti Misra] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wiest, David L.] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA.
RP Sen, JM (reprint author), NIA, Lymphocyte Dev Unit, Immunol Lab, NIH,Biomed Res Ctr, 08C218,251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM Jyoti-Sen@NIH.GOV
RI Sharma, Archna/R-9377-2016;
OI Sharma, Archna/0000-0003-4745-0220; Wiest, David/0000-0002-0792-3188
FU National Institute on Aging at the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging at the National Institutes of Health.
NR 49
TC 14
Z9 14
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 JAN 15
PY 2009
VL 182
IS 2
BP 759
EP 765
PG 7
WC Immunology
SC Immunology
GA 393RO
UT WOS:000262390600004
PM 19124718
ER
PT J
AU Wolf, AI
Buehler, D
Hensley, SE
Cavanagh, LL
Wherry, EJ
Kastner, P
Chan, S
Weninger, W
AF Wolf, Amaya I.
Buehler, Darya
Hensley, Scott E.
Cavanagh, Lois L.
Wherry, E. John
Kastner, Philippe
Chan, Susan
Weninger, Wolfgang
TI Plasmacytoid Dendritic Cells Are Dispensable during Primary Influenza
Virus Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; A VIRUS; T-CELLS; I INTERFERON;
DIFFERENTIATION; IMMUNITY; MICE; CHEMOKINES; CLEARANCE; MIGRATION
AB Plasmacytoid dendritic cells (pDC) are thought to be pivotal in the first line of defense against viral infections. Although previous studies have suggested that pDC regulate the immune response against respiratory syncytial virus, their role in pulmonary infection with influenza virus has remained unclear. Using mice with GFP-tagged pDC, we observed a marked increase in pDC numbers in the lung airways 3 days after intranasal infection with influenza virus A/PR/8/34. To further investigate their potential involvement in the disease, we made use of pDC-deficient Ikaros(L/L) mice. In the absence of pDC, the recruitment of T cells to the bronchoalveolar space was delayed, which could be reversed by the adoptive transfer of pDC before infection. Surprisingly, however, when compared with wild-type animals, Ikaros(L/L) mice revealed a similar course of disease, as determined by weight loss, viral titers, levels of neutralizing Ab, and lung pathology. Moreover, the activation and differentiation of influenza-specific CD8(+) effector T cells was unaltered in the absence of pDC, as was the generation of CD8(+) memory T cells. Taken together, our study suggests that pDC regulate the accumulation of T cells in the bronchoalveolar space during early influenza virus infection, but are dispensable for the control of this disease. The Journal of Immunology, 2009, 182: 871-879.
C1 [Wolf, Amaya I.; Buehler, Darya; Cavanagh, Lois L.; Wherry, E. John; Weninger, Wolfgang] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA.
[Hensley, Scott E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Kastner, Philippe; Chan, Susan] Illkirch CU Strasbourg, Inst Genet & Biol Mol & Cellulaire, Strasbourg, France.
[Cavanagh, Lois L.; Weninger, Wolfgang] Centenary Inst Canc Med & Cell Biol, Newtown, NSW, Australia.
[Weninger, Wolfgang] Univ Sydney, Discipline Dermatol, Camperdown, NSW, Australia.
RP Weninger, W (reprint author), Centenary Inst, Locked Bag 6, Newtown, NSW 2042, Australia.
EM w.weninger@centenary.org.au
FU National Institutes of Health; National Health and Medical Research
Council [512266]; New South Wales government
FX This work was supported by a Special Population contract from the
National Institutes of Health, National Health and Medical Research
Council Grant 512266 and a Life Sciences Award from the New South Wales
government.
NR 31
TC 54
Z9 54
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 JAN 15
PY 2009
VL 182
IS 2
BP 871
EP 879
PG 9
WC Immunology
SC Immunology
GA 393RO
UT WOS:000262390600016
PM 19124730
ER
PT J
AU Li, DM
Wang, LL
Yu, L
Freundt, EC
Jin, BQ
Screaton, GR
Xu, XN
AF Li, Demin
Wang, Lili
Yu, Li
Freundt, Eric C.
Jin, Boquan
Screaton, Gavin R.
Xu, Xiao-Ning
TI Ig-Like Transcript 4 Inhibits Lipid Antigen Presentation through Direct
CD1d Interaction
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MYELOMONOCYTIC CELLS; CRYSTAL-STRUCTURE; NKT CELLS; T-LYMPHOCYTES;
CUTTING EDGE; HLA-G; RECEPTOR; MOLECULES; RECOGNITION; BINDING
AB NKT cells recognize lipid Ags presented by CD1d molecules and play an important role in the regulation of innate and adaptive immune responses. In this study, we report the identification of a membrane-associated protein, Ig-like transcript 4 (ILT4), as a novel human CD1d receptor that inhibits CD1d-mediated immune responses. We found that native CD1d tetramer generated by mammalian cells was able to specifically bind human monocytes in the peripheral blood, and this binding was at least partly mediated by monocyte-expressed ILT4. The interaction between ILT4 and CD1d involves the two N-terminal domains of ILT4 and the Ag-binding groove of CD1d (alpha 1/alpha 2 domain). This interaction has been identified on the cell surface as well as in the endosomal and lysosomal compartments. Functional analysis showed that ILT4 could block the loading of lipid Ags such as alpha-GalCer, and consequently inhibited NKT recognition. The interaction between ILT4 and CD1d may provide new insights into the regulation of NKT-mediated immunity. The Journal of Immunology, 2009, 182: 1033-1040.
C1 [Li, Demin; Wang, Lili; Freundt, Eric C.; Xu, Xiao-Ning] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Human Immunol Unit,MRC, Oxford OX3 9DS, England.
[Yu, Li; Freundt, Eric C.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Jin, Boquan] Fourth Mil Med Univ, Dept Immunol, Xian 710032, Peoples R China.
[Screaton, Gavin R.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Med, London, England.
RP Li, DM (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Human Immunol Unit,MRC, Oxford OX3 9DS, England.
EM demin.li@imm.ox.ac.uk
FU Medical Research Council U.K.; Chinese National Natural Science
Foundation [30371346]
FX This work was supported by Medical Research Council U.K. and Chinese
National Natural Science Foundation (30371346).
NR 32
TC 21
Z9 22
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 JAN 15
PY 2009
VL 182
IS 2
BP 1033
EP 1040
PG 8
WC Immunology
SC Immunology
GA 393RO
UT WOS:000262390600032
PM 19124746
ER
PT J
AU Backman, CM
Zhang, YJ
Malik, N
Shan, LF
Hoffer, B
Westphal, H
Tomac, AC
AF Backman, Cristina M.
Zhang, YaJun
Malik, Nasir
Shan, Lufei
Hoffer, BarryJ.
Westphal, Heiner
Tomac, Andreas C.
TI Generalized tetracycline induced Cre recombinase expression through the
ROSA26 locus of recombinant mice
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Cre-loxP; ROSA26; Conditional; Tetracycline; Knockin
ID DOUBLE GENE CONSTRUCT; TRANSGENIC MICE; INDUCIBLE EXPRESSION;
MAMMALIAN-CELLS; BRAIN; MUTAGENESIS; GENERATION; PROMOTERS; REPORTER;
VECTOR
AB Inducible Cre recombinase systems have been developed to bypass initial lethal phenotypes and to provide access to later embryonic or adult phenotypes. Here we describe the generation of a recombinant mouse that combines a tetracycline dependent switch with generalized Cre recombinase expression by targeting the ubiquitously expressed ROSA26 locus. This transgenic strain was developed using a simplified gene delivery system integrating both elements, the reverse tetracycline controlled trans-activator (rtTA) and rtTA inducible promoter into a single vector. In this transgenic strain, the endogenous ROSA26 promoter drives rtTA expression through a splice acceptor site. The tetracycline inducible promoter, cloned in opposite orientation to the ROSA26 locus and separated from the rtTA element by a 5 kb human p53 intron, drives Cre recombinase expression. Crossing these mice with a Cre reporter strain showed that Cre DNA-mediated recombination was ubiquitously and effectively induced during various prenatal developmental windows. Background Cre recombinase expression levels were observed in some tissues in the absence of the inducer, mostly during late embryonic developmental stages and in adult animals. Background recombination levels were low during development and most prominent in nervous tissue. Cre recombinase expression could not be effectively induced in adult animals. While rtTA mRNA levels were high in developmental and adult tissues, Cre recombinase mRNA levels remained low after doxycycline treatment. The mouse strain described here provides a valuable tool to further analyze the function of genes during specific developmental windows, by allowing the effective inactivation of their function throughout defined stages of embryonic development. Published by Elsevier B.V.
C1 [Backman, Cristina M.; Zhang, YaJun; Malik, Nasir; Shan, Lufei; Hoffer, BarryJ.; Tomac, Andreas C.] Natl Inst Drug Abuse, Cellular Neurobiol Sect, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA.
[Westphal, Heiner] NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA.
RP Backman, CM (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Sect, Cellular Neurobiol Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM cbackman@mail.nih.gov
RI backman, cristina/C-1276-2013
FU [NIH]
FX This study was supported by the Intramural Research Program of the NIH.
NR 30
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD JAN 15
PY 2009
VL 176
IS 1
BP 16
EP 23
DI 10.1016/j.jneumeth.2008.08.024
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 375MK
UT WOS:000261117800002
PM 18801387
ER
PT J
AU Urie, KG
Angulo, D
Lee, JC
Kozak, JJ
Gray, HB
Winkler, JR
AF Urie, Kristopher G.
Angulo, David
Lee, Jennifer C.
Kozak, John J.
Gray, Harry B.
Winkler, Jay R.
TI Synchronous vs Asynchronous Chain Motion in alpha-Synuclein Contact
Dynamics
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID UNFOLDED POLYPEPTIDE-CHAINS; END-TO-END; CYTOCHROME-C; INTRACHAIN
DIFFUSION; LOOP FORMATION; RANDOM WALKS; SPEED LIMIT; PROTEINS;
EFFICIENCY; LATTICES
AB alpha-Synuclein (alpha-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson's disease. Tertiary contact formation rate constants in (alpha-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in alpha-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide.
C1 [Urie, Kristopher G.; Angulo, David; Kozak, John J.] Depaul Univ, Dept Chem, Chicago, IL 60604 USA.
[Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Gray, Harry B.; Winkler, Jay R.] CALTECH, Beckman Inst, Pasadena, CA 91125 USA.
RP Kozak, JJ (reprint author), Depaul Univ, Dept Chem, 243 S Wabash Ave, Chicago, IL 60604 USA.
EM kozak@depaul.edu; hbgray@caltech.edu; winklerj@caltech.edu
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU National Institutes of Health [GM068461, DK19038]; Ellison Medical
Foundation; Intramural Research Program of the National Institutes of
Health; National Heart, Lung, and Blood Institute
FX This research was supported by grants from the National Institutes of
Health (GM068461 to J.R.W.; DK19038 to H.B.G.) and the Ellison Medical
Foundation (Senior Scholar Award in Aging to H.B.G.), and by the
Intramural Research Program of the National Institutes of Health, the
National Heart, Lung, and Blood Institute (J.C.L.).
NR 30
TC 5
Z9 5
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JAN 15
PY 2009
VL 113
IS 2
BP 522
EP 530
DI 10.1021/jp806727e
PG 9
WC Chemistry, Physical
SC Chemistry
GA 392TF
UT WOS:000262324400017
PM 19099437
ER
PT J
AU Larue, RS
Andresdottir, V
Blanchard, Y
Conticello, SG
Derse, D
Emerman, M
Greene, WC
Jonsson, SR
Landau, NR
Lochelt, M
Malik, HS
Malim, MH
Munk, C
O'Brien, SJ
Pathak, VK
Strebel, K
Wain-Hobson, S
Yu, XF
Yuhki, N
Harris, RS
AF LaRue, Rebecca S.
Andresdottir, Valgerdur
Blanchard, Yannick
Conticello, Silvestro G.
Derse, David
Emerman, Michael
Greene, Warner C.
Jonsson, Stefan R.
Landau, Nathaniel R.
Loechelt, Martin
Malik, Harmit S.
Malim, Michael H.
Muenk, Carsten
O'Brien, Stephen J.
Pathak, Vinay K.
Strebel, Klaus
Wain-Hobson, Simon
Yu, Xiao-Fang
Yuhki, Naoya
Harris, Reuben S.
TI Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins
SO JOURNAL OF VIROLOGY
LA English
DT Editorial Material
ID POLYNUCLEOTIDE (DEOXY)CYTIDINE DEAMINASES; ADAPTIVE EVOLUTION;
AID/APOBEC FAMILY; IN-VIVO; RESTRICTION; MECHANISM; INFECTION; VIF
C1 [LaRue, Rebecca S.; Jonsson, Stefan R.; Harris, Reuben S.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Inst Mol Virol, Beckman Ctr Genome Engn,Comparat & Mol Biol Grad, Minneapolis, MN 55455 USA.
[Andresdottir, Valgerdur; Jonsson, Stefan R.] Univ Iceland, Inst Expt Pathol, IS-112 Reykjavik, Iceland.
[Blanchard, Yannick] AFSSA LERAPP, Unite Genet Viral & Biosecur, F-22440 Ploufragan, France.
[Conticello, Silvestro G.] Inst Toscano Tumori, Core Res Lab, I-50139 Florence, Italy.
[Derse, David; Pathak, Vinay K.] NCI, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Emerman, Michael; Malik, Harmit S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Greene, Warner C.] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Landau, Nathaniel R.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
[Loechelt, Martin] German Canc Res Ctr, Res Program Infect & Canc, Div Genome Modificat & Carcinogenesis, D-69120 Heidelberg, Germany.
[Malim, Michael H.] Kings Coll London, Guys Hosp, Sch Med, Dept Infect Dis, London SE1 9RT, England.
[Muenk, Carsten] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany.
[O'Brien, Stephen J.; Yuhki, Naoya] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Strebel, Klaus] NIAID, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA.
[Wain-Hobson, Simon] Inst Pasteur, Mol Retrovirol Unit, F-75015 Paris, France.
[Yu, Xiao-Fang] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
RP Harris, RS (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Inst Mol Virol, Beckman Ctr Genome Engn,Comparat & Mol Biol Grad, 321 Church St SE,6-155 Jackson Hall, Minneapolis, MN 55455 USA.
EM rsh@umn.edu
RI Conticello, Silvestro/G-9113-2011; Malik, Harmit/E-8519-2012;
OI Malim, Michael/0000-0002-7699-2064; Malik, Harmit/0000-0001-6005-0016;
Conticello, Silvestro/0000-0002-4244-1846
FU Medical Research Council [G0401570]
NR 23
TC 100
Z9 103
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2009
VL 83
IS 2
BP 494
EP 497
DI 10.1128/JVI.01976-08
PG 4
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000001
PM 18987154
ER
PT J
AU Morner, A
Douagi, I
Forsell, MNE
Sundling, C
Dosenovic, P
O'Dell, S
Dey, B
Kwong, PD
Voss, G
Thorstensson, R
Mascola, JR
Wyatt, RT
Hedestam, GBK
AF Moerner, Andreas
Douagi, Iyadh
Forsell, Mattias N. E.
Sundling, Christopher
Dosenovic, Pia
O'Dell, Sijy
Dey, Barna
Kwong, Peter D.
Voss, Gerald
Thorstensson, Rigmor
Mascola, John R.
Wyatt, Richard T.
Hedestam, Gunilla B. Karlsson
TI Human Immunodeficiency Virus Type 1 Env Trimer Immunization of Macaques
and Impact of Priming with Viral Vector or Stabilized Core Protein
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SEMLIKI-FOREST-VIRUS; ENVELOPE GLYCOPROTEIN TRIMERS; VENEZUELAN EQUINE
ENCEPHALITIS; ALPHAVIRUS REPLICON PARTICLES; T-CELL RESPONSES;
NEUTRALIZING ANTIBODIES; CANDIDATE VACCINE; CD4-BOUND STATE;
RHESUS-MONKEYS; HIV-1 VACCINE
AB Currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-based immunogens in primates. Here we describe a comprehensive analysis of neutralizing antibody and T-cell responses obtained in cynomolgus macaques by three selected immunization regimens. We used the previously described YU2-based gp140 protein trimers administered in an adjuvant, preceded by two distinct priming strategies: either alphavirus replicon particles expressing matched gp140 trimers or gp120 core proteins stabilized in the CD4-bound conformation. The rationale for priming with replicon particles was to evaluate the impact of the expression platform on trimer immunogenicity. The stable core proteins were chosen in an attempt to expand selectively lymphocytes recognizing common determinants between the core and trimers to broaden the immune response. The results presented here demonstrate that the platform by which Env trimers were delivered in the priming ( either protein or replicon vector) had little impact on the overall immune response. In contrast, priming with stable core proteins followed by a trimer boost strikingly focused the T-cell response on the core sequences of HIV-1 Env. The specificity of the T-cell response was distinctly different from that of the responses obtained in animals immunized with trimers alone and was shown to be mediated by CD4(+) T cells. However, this regimen showed limited or no improvement in the neutralizing antibody responses, suggesting that further immunogen design efforts are required to successfully focus the B-cell response on conserved neutralizing determinants of HIV-1 Env.
C1 [Moerner, Andreas; Douagi, Iyadh; Forsell, Mattias N. E.; Sundling, Christopher; Dosenovic, Pia; Thorstensson, Rigmor; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
[Moerner, Andreas; Douagi, Iyadh; Forsell, Mattias N. E.; Sundling, Christopher; Dosenovic, Pia; Thorstensson, Rigmor; Hedestam, Gunilla B. Karlsson] Swedish Inst Infect Dis Control, S-17182 Solna, Sweden.
[Forsell, Mattias N. E.; Dey, Barna; Kwong, Peter D.; Mascola, John R.; Wyatt, Richard T.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Voss, Gerald] GlaxoSmithKline Biol, Rixensart, Belgium.
RP Hedestam, GBK (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Box 280, S-17177 Stockholm, Sweden.
EM gunilla.karlsson.hedestam@ki.se
OI Morner, Andreas/0000-0002-3654-1728; Sundling,
Christopher/0000-0002-6138-690X
FU Swedish International Development Agency (Sida)/Department of Research
Cooperation (SAREC); National Institute of Allergy and Infectious
Diseases; National Institutes of Health intramural research program;
Bill and Melinda Gates Foundation; International AIDS Vaccine
Initiative; Swedish Research Council
FX This study was supported by a grant from the Swedish International
Development Agency (Sida)/Department of Research Cooperation (SAREC) to
G.K.H. and R.T. and by the National Institute of Allergy and Infectious
Diseases, National Institutes of Health intramural research program, for
P.D.K., J.R.M., and R.T.W. Funding was also received from the Bill and
Melinda Gates Foundation (P.D.K., J.R.M., and R.T.W.), the International
AIDS Vaccine Initiative (P.D.K., R.T.W., and G.K.H.), and the Swedish
Research Council (G.K.H.).
NR 57
TC 47
Z9 47
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2009
VL 83
IS 2
BP 540
EP 551
DI 10.1128/JVI.01102-08
PG 12
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000005
PM 19004960
ER
PT J
AU Poddar, A
Reed, SC
McPhillips, MG
Spindler, JE
McBride, AA
AF Poddar, Atasi
Reed, Shawna C.
McPhillips, Maria G.
Spindler, Jonathan E.
McBride, Alison A.
TI The Human Papillomavirus Type 8 E2 Tethering Protein Targets the
Ribosomal DNA Loci of Host Mitotic Chromosomes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RNA-POLYMERASE-I; TRANSCRIPTION FACTOR HUBF; NUCLEAR ANTIGEN 1;
SACCHAROMYCES-CEREVISIAE; PLASMID MAINTENANCE; BROMODOMAIN PROTEIN;
VIRAL-DNA; BINDING; BRD4; ASSOCIATION
AB For many papillomaviruses, the viral protein E2 tethers the viral genome to the host mitotic chromosomes to ensure persistent, long-term maintenance of the genome during cell division. Our previous studies of E2 proteins from different genera of papillomaviruses have shown that they bind to different regions of the host chromosomes during mitosis. For example, bovine papillomavirus type 1 (BPV-1) E2 binds to all chromosomes as small speckles in complex with the cellular protein Brd4. In contrast, the human papillomavirus type 8 (HPV-8) E2 protein binds as large speckles at the pericentromeric regions of chromosomes. Here we show that these speckles do not contain Brd4, and unlike that of BPV-1, the N-terminal Brd4-interacting domain of HPV-8 E2 is not required for chromosome binding. In contrast to BPV-1 E2, the HPV-8 E2 protein targets the short arms of acrocentric mitotic chromosomes. Furthermore, the E2 protein interacts with the repeated ribosomal DNA genes found in this location and colocalizes with UBF, the RNA polymerase I transcription factor. Therefore, HPV-8 E2 genome tethering occurs by a Brd4-independent mechanism through a novel interaction with specific regions of mitotic chromosomes. Thus, a wide range of viruses have adopted the strategy of linking their genomes to host chromosomes, but individual viruses use different chromosomal targets. Characterization of these targets will enable the development of antiviral therapies to eliminate the viral genomes from infected cells.
C1 [Poddar, Atasi; Reed, Shawna C.; McPhillips, Maria G.; Spindler, Jonathan E.; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA.
EM amcbride@nih.gov
OI McBride, Alison/0000-0001-5607-5157
FU NIAID; NIH
FX We thank Juraj Kabat for help with image processing.
NR 42
TC 28
Z9 28
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 JAN 15
PY 2009
VL 83
IS 2
BP 640
EP 650
DI 10.1128/JVI.01936-08
PG 11
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000014
PM 19004936
ER
PT J
AU Ko, SY
Cheng, C
Kong, WP
Wang, LS
Kanekiyo, M
Einfeld, D
King, CR
Gall, JGD
Nabel, GJ
AF Ko, Sung-Youl
Cheng, Cheng
Kong, Wing-Pui
Wang, Lingshu
Kanekiyo, Masaru
Einfeld, David
King, C. Richter
Gall, Jason G. D.
Nabel, Gary J.
TI Enhanced Induction of Intestinal Cellular Immunity by Oral Priming with
Enteric Adenovirus 41 Vectors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8-ALPHA(+) DENDRITIC CELLS; CD4(+)
T-CELLS; ACUTE GASTROENTERITIS; IMMUNOGENICITY EVALUATION;
GASTROINTESTINAL-TRACT; PROTECTIVE IMMUNITY; CANDIDATE VACCINE; HIV-1
INFECTION; PHASE-1 SAFETY
AB Human immunodeficiency virus type 1 (HIV-1) infection is characterized by the rapid onset of intestinal T-cell depletion that initiates the progression to AIDS. The induction of protective immunity in the intestinal mucosa therefore represents a potentially desirable feature of a preventive AIDS vaccine. In this study, we have evaluated the ability of an enteric adenovirus, recombinant adenovirus 41 (rAd41), to elicit intestinal and systemic immune responses by different immunization routes, alone or in combination with rAd5. rAd41 expressing HIV envelope (Env) protein induced cellular immune responses comparable to those of rAd5-based vectors after either a single intramuscular injection or a DNA prime/rAd boost. Oral priming with rAd41-Env followed by intramuscular boosting with rAd5-Env stimulated a more potent CD8(+) T-cell response in the small intestine than the other immunization regimens. Furthermore, the direct injection of rAd41-Env into ileum together with intramuscular rAd5-Env boosting increased Env-specific cellular immunity markedly in mucosal as well as systemic compartments. These data demonstrate that heterologous rAd41 oral or ileal priming with rAd5 intramuscular boosting elicits enhanced intestinal mucosal cellular immunity and that oral or ileal vector delivery for primary immunization facilitates the generation of mucosal immunity.
C1 [Ko, Sung-Youl; Cheng, Cheng; Kong, Wing-Pui; Wang, Lingshu; Kanekiyo, Masaru; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Einfeld, David; King, C. Richter; Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU National Institutes of Health; Vaccine Research Center; NIAID; Bill and
Melinda Gates Foundation
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Vaccine Research Center, NIAID, and by
the Bill and Melinda Gates Foundation.
NR 40
TC 16
Z9 17
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2009
VL 83
IS 2
BP 748
EP 756
DI 10.1128/JVI.01811-08
PG 9
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000023
PM 18987146
ER
PT J
AU Hidajat, R
Xiao, P
Zhou, Q
Venzon, D
Summers, LE
Kalyanaraman, VS
Montefiori, DC
Robert-Guroff, M
AF Hidajat, Rachmat
Xiao, Peng
Zhou, Qifeng
Venzon, David
Summers, L. Ebonita
Kalyanaraman, Vaniambadi S.
Montefiori, David C.
Robert-Guroff, Marjorie
TI Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing
Antibody Activities with Reduced Acute Viremia following Intrarectal
Simian Immunodeficiency Virus SIVmac251 Challenge of Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DEPENDENT CELLULAR CYTOTOXICITY; NEUTRALIZING ANTIBODIES;
IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; MEDIATED CYTOTOXICITY;
RECOMBINANT VACCINES; VAGINAL TRANSMISSION; EFFECTOR-CELLS;
HIV-INFECTION; PROTECTION
AB Cell-mediated immunity and neutralizing antibodies contribute to control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but the role of nonneutralizing antibodies is not defined. Previously, we reported that sequential oral/oral or intranasal/oral (I/O) priming with replication-competent adenovirus type 5 host range mutant (Ad5hr)-SIV recombinants, followed by intramuscular envelope protein boosting, elicited systemic and mucosal cellular immunity and exhibited equivalent, significant reductions of chronic viremia after rectal SIVmac251 challenge. However, I/O priming gave significantly better control of acute viremia. Here, systemic and mucosal humoral immunity were investigated for potential correlates with the acute challenge outcome. Strong serum binding but nonneutralizing antibody responses against SIVmac251 were induced in both groups. Antibody responses appeared earlier and overall were higher in the I/O group. Reduced acute viremia was significantly correlated with higher serum binding titer, stronger antibody-dependent cellular cytotoxicity activity, and peak prechallenge and 2-week-postchallenge antibody-dependent cell-mediated viral inhibition (ADCVI). The I/O group consistently displayed greater anti-envelope immunoglobulin A (IgA) antibody responses in bronchoalveolar lavage and a stronger rectal anti-envelope IgA anamnestic response 2 weeks postchallenge. Pre- and postchallenge rectal secretions inhibited SIV transcytosis across epithelial cells. The inhibition was significantly higher in the I/O group, although a significant correlation with reduced acute viremia was not reached. Overall, the replicating Ad5hr-SIV priming/envelope boosting approach elicited strong systemic and mucosal antibodies with multiple functional activities. The pattern of elevated immune responses in the I/O group is consistent with its better control of acute viremia mediated, at least in part, by ADCVI activity and transcytosis inhibition.
C1 [Hidajat, Rachmat; Xiao, Peng; Zhou, Qifeng; Summers, L. Ebonita; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Kalyanaraman, Vaniambadi S.] Adv Biosci Labs Inc, Kensington, MD 20895 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
RP Robert-Guroff, M (reprint author), NCI, NIH, 41 Medlars Dr Bldg,41 Rm D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU National Institutes of Health; National Cancer Institute
FX We are very grateful to Marisa St. Claire, Steve Harbaugh, and Jeff
Harbaugh (Bioqual, Inc., Gaithersburg, MD) for excellent care of the
rhesus macaques and expert execution of all animal technical procedures.
We thank Nancy Miller (DAIDS, NIAID, NIH) and Ronald C. Desrosiers, New
England National Primate Research Center, Boston, MA, for the titrated
SIVmac251 challenge stock. We also thank Ruth H. Florese for
assistance with the RF-ADCC assay. The CEM-NKr cells were
obtained from Peter Cresswell through the AIDS Research and Reference
Reagent Program, Division of AIDS, NIAID, NIH.; This study was supported
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 60
TC 86
Z9 87
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 JAN 15
PY 2009
VL 83
IS 2
BP 791
EP 801
DI 10.1128/JVI.01672-08
PG 11
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000027
PM 18971271
ER
PT J
AU Trapp, S
Derby, NR
Singer, R
Shaw, A
Williams, VG
Turville, SG
Bess, JW
Lifson, JD
Robbiani, M
AF Trapp, Susanna
Derby, Nina R.
Singer, Rachel
Shaw, Andrew
Williams, Vennansha G.
Turville, Stuart G.
Bess, Julian W., Jr.
Lifson, Jeffrey D.
Robbiani, Melissa
TI Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency
Virus Amplification in Dendritic Cells via Type I Interferon-Mediated
Activation of APOBEC3G
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IFN-GAMMA-PRODUCTION; ACUTE HIV-1 INFECTION; CD4(+) T-CELLS; SIMIAN
IMMUNODEFICIENCY; ANTIVIRAL ACTIONS; INNATE IMMUNITY; PROTEIN;
MATURATION; INDUCTION; ALPHA
AB Human immunodeficiency virus (HIV) is taken up by and replicates in immature dendritic cells (imDCs), which can then transfer virus to T cells, amplifying the infection. Strategies known to boost DC function were tested for their ability to overcome this exploitation when added after HIV exposure. Poly(I: C), but not single-stranded RNA (ssRNA) or a standard DC maturation cocktail, elicited type I interferon (IFN) and interleukin-12 (IL-12) p70 production and the appearance of unique small (15- to 20-kDa) fragments of APOBEC3G (A3G) and impeded HIV(Bal) replication in imDCs when added up to 60 h after virus exposure. Comparable effects were mediated by recombinant alpha/beta IFN (IFN-alpha/beta). Neutralizing the anti-IFN-alpha/beta receptor reversed poly(I:C)-induced inhibition of HIV replication and blocked the appearance of the small A3G proteins. The poly(I: C)-induced appearance of small A3G proteins was not accompanied by significant differences in A3G mRNA or A3G monomer expression. Small interfering RNA (siRNA) knockdown of A3G could not be used to reverse the poly(I: C)-induced protective effect, since siRNAs nonspecifically activated the DCs, inducing the appearance of the small A3G proteins and inhibiting HIV infection. Notably, the appearance of small A3G proteins coincided with the shift of high-molecular-mass inactive A3G complexes to the low-molecular-mass (LMM) active A3G complexes. The unique immune stimulation by poly(I:C) with its antiviral effects on imDCs marked by the expression of IFN-alpha/beta and active LMM A3G renders poly(I:C) a promising novel strategy to combat early HIV infection in vivo.
C1 [Trapp, Susanna; Derby, Nina R.; Singer, Rachel; Shaw, Andrew; Williams, Vennansha G.; Turville, Stuart G.; Robbiani, Melissa] Populat Council, Ctr Biomed Res, HIV & AIDS Program, New York, NY 10065 USA.
[Bess, Julian W., Jr.; Lifson, Jeffrey D.] NCI, SAIC Frederick, Ft Detrick, MD 21702 USA.
RP Robbiani, M (reprint author), Populat Council, Ctr Biomed Res, HIV & AIDS Program, New York, NY 10065 USA.
FU NIH [AI040877, DE015512, NO1-CO-12400]
FX This work was supported by NIH grants AI040877 and DE015512 and in part
with federal funds from the National Cancer Institute, NIH, under
contract no. NO1-CO-12400. M. R. is a 2002 Elizabeth Glaser Scientist.
The following reagents were obtained through the NIH AIDS Research and
Reference Reagent Program, Division of AIDS, NIAID, NIH: anti-A3G, C
terminal, from Jaisri Lingappa; 8E5/LAV from Thomas Folks; TZM.bl cells
from John C. Kappes, Xiaoyun Wu, and Tranzyme Inc.; and 293-APOBEC3G-HA
cell line from Xiao-Fang Yu.
NR 76
TC 44
Z9 49
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2009
VL 83
IS 2
BP 884
EP 895
DI 10.1128/JVI.00023-08
PG 12
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000036
PM 19004943
ER
PT J
AU Zhou, MS
Huang, K
Jung, KJ
Cho, WK
Klase, Z
Kashanchi, F
Pise-Masison, CA
Brady, JN
AF Zhou, Meisheng
Huang, Keven
Jung, Kyung-Jin
Cho, Won-Kyung
Klase, Zach
Kashanchi, Fatah
Pise-Masison, Cynthia A.
Brady, John N.
TI Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus
Transcription through Phosphorylation of CDK9 at Threonine 29
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; P-TEFB; PHOSPHATASE 2A;
SUBSTRATE-SPECIFICITY; TYPE-1 TRANSCRIPTION; HIV-1 TRANSCRIPTION; 7SK
SNRNA; IN-VITRO; CYCLIN-C
AB Positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 (CDK9) and cyclin T, is a global transcription factor for eukaryotic gene expression, as well as a key factor for human immunodeficiency virus (HIV) transcription elongation. P-TEFb phosphorylates the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II), facilitating the transition from nonprocessive to processive transcription elongation. Recently, the bromodomain protein Brd4 has been shown to interact with the low-molecular-weight, active P-TEFb complex and recruit P-TEFb to the HIV type 1 long terminal repeat (LTR) promoter. However, the subsequent events through which Brd4 regulates CDK9 kinase activity and RNAP II-dependent transcription are not clearly understood. Here we provide evidence that Brd4 regulates P-TEFb kinase activity by inducing a negative pathway. Moreover, by analyzing stepwise initiation and elongation complexes, we demonstrate that P-TEFb activity is regulated in the transcription complex. Brd4 induces phosphorylation of CDK9 at threonine 29 (T29) in the HIV transcription initiation complex, inhibiting CDK9 kinase activity. P-TEFb inhibition is transient, as Brd4 is released from the transcription complex between positions + 14 and + 36. Removal of the phosphate group at T29 by an incoming phosphatase released P-TEFb activity, resulting in increased RNAP II CTD phosphorylation and transcription. Finally, we present chromatin immunoprecipitation studies showing that CDK9 with phosphorylated T29 is associated with the HIV promoter region in the integrated and transcriptionally silent HIV genome.
C1 [Zhou, Meisheng; Huang, Keven; Jung, Kyung-Jin; Cho, Won-Kyung; Pise-Masison, Cynthia A.; Brady, John N.] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Klase, Zach; Kashanchi, Fatah] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bldg 41,Room B201, Bethesda, MD 20892 USA.
EM bradyj@exchange.nih.gov
NR 48
TC 36
Z9 38
U1 2
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 JAN 15
PY 2009
VL 83
IS 2
BP 1036
EP 1044
DI 10.1128/JVI.01316-08
PG 9
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000050
PM 18971272
ER
PT J
AU Li, YX
Svehla, K
Louder, MK
Wycuff, D
Phogat, S
Tang, M
Migueles, SA
Wu, XL
Phogat, A
Shaw, GM
Connors, M
Hoxie, J
Mascola, JR
Wyatt, R
AF Li, Yuxing
Svehla, Krisha
Louder, Mark K.
Wycuff, Diane
Phogat, Sanjay
Tang, Min
Migueles, Stephen A.
Wu, Xueling
Phogat, Adhuna
Shaw, George M.
Connors, Mark
Hoxie, James
Mascola, John R.
Wyatt, Richard
TI Analysis of Neutralization Specificities in Polyclonal Sera Derived from
Human Immunodeficiency Virus Type 1-Infected Individuals
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES;
CORECEPTOR-BINDING-SITE; TYROSINE SULFATION; RECEPTOR-BINDING; CD4
RECEPTOR; HIV-1 ENTRY; INFECTION; RESPONSES; EPITOPE
AB During human immunodeficiency virus type 1 (HIV-1) infection, patients develop various levels of neutralizing antibody (NAb) responses. In some cases, patient sera can potently neutralize diverse strains of HIV-1, but the antibody specificities that mediate this broad neutralization are not known, and their elucidation remains a formidable challenge. Due to variable and nonneutralizing determinants on the exterior envelope glycoprotein (Env), nonnative Env protein released from cells, and the glycan shielding that assembles in the context of the quaternary structure of the functional spike, HIV-1 Env elicits a myriad of binding antibodies. However, few of these antibodies can neutralize circulating viruses. We present a systematic analysis of the NAb specificities of a panel of HIV-1-positive sera, using methodologies that identify both conformational and continuous neutralization determinants on the HIV-1 Env protein. Characterization of sera included selective adsorption with native gp120 and specific point mutant variants, chimeric virus analysis, and peptide inhibition of viral neutralization. The gp120 protein was the major neutralizing determinant for most sera, although not all neutralization activity against all viruses could be identified. In some broadly neutralizing sera, the gp120-directed neutralization mapped to the CD4 binding region of gp120. In addition, we found evidence that regions of the gp120 coreceptor binding site may also be a target of neutralizing activity. Sera displaying limited neutralization breadth were mapped to the immunogenic V3 region of gp120. In a subset of sera, we also identified NAbs directed against the conserved, membrane-proximal external region of gp41. These data allow a more detailed understanding of the humoral responses to the HIV-1 Env protein and provide insights regarding the most relevant targets for HIV-1 vaccine design.
C1 [Wyatt, Richard] NIAID, Struct Virol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Migueles, Stephen A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Shaw, George M.] Univ Alabama, Birmingham, AL USA.
[Hoxie, James] Univ Penn, Philadelphia, PA 19104 USA.
RP Wyatt, R (reprint author), NIAID, Struct Virol Sect, Vaccine Res Ctr, NIH, Bldg 40,Rm 4512,40 Convent Dr, Bethesda, MD 20892 USA.
EM richardwyatt@nih.gov
FU NIH intramural research program; NIH; International AIDS Vaccine
Initiative; Bill and Melinda Gates Foundation
FX This work was supported in part by the NIH intramural research program.
Funding was also provided by NIH, the International AIDS Vaccine
Initiative, and the Bill and Melinda Gates Foundation.
NR 48
TC 189
Z9 190
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 JAN 15
PY 2009
VL 83
IS 2
BP 1045
EP 1059
DI 10.1128/JVI.01992-08
PG 15
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000051
PM 19004942
ER
PT J
AU Goila-Gaur, R
Khan, MA
Miyagi, E
Strebel, K
AF Goila-Gaur, Ritu
Khan, Mohammad A.
Miyagi, Eri
Strebel, Klaus
TI Differential Sensitivity of "Old" versus "New" APOBEC3G to Human
Immunodeficiency Virus Type 1 Vif
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EDITING ENZYME APOBEC3G; ANTIVIRAL ACTIVITY; HIV-1 VIF; DEGRADATION;
PROTEIN; DNA; INFECTIVITY; PROTEASOME; HYPERMUTATION; REPLICATION
AB HIV-1 Vif counteracts the antiviral activity of APOBEC3G by inhibiting its encapsidation into virions. Here, we compared the relative sensitivity to Vif of APOBEC3G in stable HeLa cells containing APOBEC3G (HeLa-A3G cells) versus that of newly synthesized APOBEC3G. We observed that newly synthesized APOBEC3G was more sensitive to degradation than preexisting APOBEC3G. Nevertheless, preexisting and transiently expressed APOBEC3G were packaged with similar efficiencies into vif-deficient human immunodeficiency virus type 1 (HIV-1) virions, and Vif inhibited the encapsidation of both forms of APOBEC3G into HIV particles equally well. Our results suggest that HIV-1 Vif preferentially induces degradation of newly synthesized APOBEC3G but indiscriminately inhibits encapsidation of "old" and "new" APOBEC3G.
C1 [Goila-Gaur, Ritu; Khan, Mohammad A.; Miyagi, Eri; Strebel, Klaus] NIAID, NIH, Viral Biochem Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA.
RP Strebel, K (reprint author), NIAID, NIH, Viral Biochem Sect, Mol Microbiol Lab, 4-312,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
FU NIH; NIAID
FX This work was supported by a grant from the NIH Intramural AIDS Targeted
Antiviral Program to K. S. and by the Intramural Research Program of the
NIAID, NIH.
NR 27
TC 13
Z9 13
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 JAN 15
PY 2009
VL 83
IS 2
BP 1156
EP 1160
DI 10.1128/JVI.01734-08
PG 5
WC Virology
SC Virology
GA 388UO
UT WOS:000262045000063
PM 19004939
ER
PT J
AU Wickremaratchi, MM
Majounie, E
Morris, HR
Williams, NM
Lewis, H
Gill, SS
Khan, S
Heywood, P
Hardy, J
Wiles, CM
Singleton, AB
Quinn, NP
AF Wickremaratchi, Mindhu M.
Majounie, Elisa
Morris, Huw R.
Williams, Nigel M.
Lewis, Helen
Gill, Steven S.
Khan, Sadaquate
Heywood, Peter
Hardy, John
Wiles, Charles M.
Singleton, Andrew B.
Quinn, Niall P.
TI Parkin-related Disease Clinically Diagnosed as a Pallido-Pyramidal
Syndrome
SO MOVEMENT DISORDERS
LA English
DT Letter
ID RECESSIVE JUVENILE PARKINSONISM; EARLY-ONSET PARKINSONISM; LEWY BODY;
MUTATIONS; GENE; DELETION
C1 [Wickremaratchi, Mindhu M.; Majounie, Elisa; Morris, Huw R.; Wiles, Charles M.] Cardiff Univ, Sch Med, Dept Neurol, Cardiff, S Glam, Wales.
[Majounie, Elisa; Morris, Huw R.; Williams, Nigel M.] Cardiff Univ, Sch Med, Psychol Med Genet Lab, Cardiff, S Glam, Wales.
[Lewis, Helen; Gill, Steven S.; Khan, Sadaquate; Heywood, Peter] Frenchay Hosp, Inst Clin Neurosci, Bristol BS16 1LE, Avon, England.
[Hardy, John; Singleton, Andrew B.] NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
[Hardy, John] Dept Mol Neurosci, London, England.
[Hardy, John] Reta Lila Weston Labs, London, England.
[Quinn, Niall P.] Inst Neurol, Sobell Dept Neurosci & Movement Disorders, London WC1N 3BG, England.
RP Wickremaratchi, MM (reprint author), Cardiff Univ, Sch Med, Dept Neurol, Cardiff, S Glam, Wales.
EM morrishr@cf.ac.uk
RI Hardy, John/C-2451-2009; Morris, Huw/B-8527-2008; Singleton,
Andrew/C-3010-2009
OI Morris, Huw/0000-0002-5473-3774;
FU Intramural NIH HHS; Medical Research Council [G0700943, G0701075]; NIA
NIH HHS [Z01 AG000957-05]; Parkinson's UK [G-8047, G-0907]
NR 22
TC 5
Z9 5
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 JAN 15
PY 2009
VL 24
IS 1
BP 138
EP 140
DI 10.1002/mds.22181
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 402CW
UT WOS:000262992800023
PM 18942080
ER
PT J
AU Chuang, KH
Lee, JH
Silva, AC
Belluscio, L
Koretsky, AP
AF Chuang, Kai-Hsiang
Lee, Jung Hee
Silva, Afonso C.
Belluscio, Leonardo
Koretsky, Alan P.
TI Manganese enhanced MRI reveals functional circuitry in response to
odorant stimuli
SO NEUROIMAGE
LA English
DT Article; Proceedings Paper
CT 14th Annual Meeting of the
International-Society-for-Magnetic-Resonance-in-Medicine
CY MAY 06-12, 2006
CL Seattle, WA
SP Int Soc Magnet Resonance Med
ID MOUSE OLFACTORY-BULB; RESONANCE-IMAGING MEMRI; OCULAR DOMINANCE;
RAT-BRAIN; SYSTEM; COMBINATORIAL; ACTIVATION; MAPS; REPRESENTATIONS;
ORGANIZATION
AB To investigate the circuitry involved in detecting odorants in the rodent brain, we developed a method using manganese-enhanced MRI (MEMRI) to map the flow of neural information from the olfactory sensory neurons (OSNs) to the central layers of the olfactory bulb. Studies have shown that Mn(2+) enters active neurons and is transported anterogradely to axon terminals where it can cross synapses to functionally trace neural networks. Thus, by delivering MnCl(2) directly into the nasal cavity of mice and then exposing them to defined odorants, Mn(2+) is preferentially taken up by activated OSNs. Using the time course of the MRI signal, we generated maps of Mn(2+) accumulation in the olfactory bulb for both glomerular and mitral cell layers. Results demonstrated that overlapping yet distinct enhancement patterns were produced by exposure to either octanal, acetophenone, or carvone. Notably, areas of Mn(2+) accumulation in the mitral cell layer were similar to those in the glomerular layer consistent with neural information that passes from specific OSNs to specific mitral cells. Finally, by correlating specific Mn(2+) signal peaks to genetically labeled glomeruli that are known to be activated by the odorant octanal, we show that MEMRI maps can be resolved at the level of individual glomeruli. Published by Elsevier Inc.
C1 [Chuang, Kai-Hsiang; Lee, Jung Hee; Silva, Afonso C.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Belluscio, Leonardo] Natl Inst Neurol Disorders & Stroke, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA.
[Lee, Jung Hee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Radiol, Seoul, South Korea.
RP Chuang, KH (reprint author), Singapore Bioimaging Consortium, Lab Mol Imaging, 11 Biopolis Way 02-02, Singapore 138667, Singapore.
EM chuangk@ninds.nih.gov
RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015; lee,
junghee/D-6130-2017;
OI Koretsky, Alan/0000-0002-8085-4756; Chuang,
Kai-Hsiang/0000-0002-8356-0657
FU Intramural NIH HHS [Z01 NS002989-08, Z99 NS999999]
NR 48
TC 33
Z9 33
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 JAN 15
PY 2009
VL 44
IS 2
BP 363
EP 372
DI 10.1016/j.neuroimage.2008.08.046
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KH
UT WOS:000262301100008
PM 18848997
ER
PT J
AU Bianciardi, M
van Gelderen, P
Duyn, JH
Fukunaga, M
de Zwart, JA
AF Bianciardi, Marta
van Gelderen, Peter
Duyn, Jeff H.
Fukunaga, Masaki
de Zwart, Jacco A.
TI Making the most of fMRI at 7 T by suppressing spontaneous signal
fluctuations
SO NEUROIMAGE
LA English
DT Article
DE Evoked responses; Spontaneous signal fluctuations; Noise modeling;
Correlated noise; Estimation precision; Temporal autocorrelation; BOLD
fMRI; High field strength
ID TEMPORAL AUTOCORRELATION; PHYSIOLOGICAL NOISE; BOLD SIGNAL; HUMAN BRAIN;
VARIABILITY; SYSTEMS; MRI; RESPONSES; NETWORKS; HUMANS
AB The presence of spontaneous BOLD fMRI signal fluctuations in human grey matter compromises the detection and interpretation of evoked responses and limits the sensitivity gains that are potentially available through coil arrays and high field systems. In order to overcome these limitations, we adapted and improved a recently described correlated noise suppression method (de Zwart et al., 2008), demonstrating improved precision in estimating the response to ultra-short visual stimuli at 7 T. In this procedure, the temporal dynamics of spontaneous signal fluctuations are estimated from a reference brain region outside the area targeted with the stimulus. Rather than using the average signal in this region as regressor, as proposed in the original method, we used principal component analysis to derive multiple regressors in order to optimally describe nuisance signals (e. g. spontaneous fluctuations) and separate these from evoked activity in the target region.
Experimental results obtained from application of the original method showed a 66% improvement in estimation precision. The novel, enhanced version of the method, using 18 PCA-derived noise regressors, led to a 160% increase in precision. These increases were relative to a control condition without noise suppression, which was simulated by randomizing the time-course of the nuisance-signal regressor(s) without altering their power spectrum. The increase of estimation precision was associated with decreased autocorrelation levels of the residual errors.
These results suggest that modeling of spontaneous fMRI signal fluctuations as multiple independent sources can dramatically improve detection of evoked activity, and fully exploit the potential sensitivity gains available with high field technology. Published by Elsevier Inc.
C1 [Bianciardi, Marta; van Gelderen, Peter; Duyn, Jeff H.; Fukunaga, Masaki; de Zwart, Jacco A.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
RP de Zwart, JA (reprint author), 10 Ctr Dr,Bldg 10,Room B1D-726,MSC 1065, Bethesda, MD 20892 USA.
EM Jacco.deZwart@nih.gov
RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013
OI Fukunaga, Masaki/0000-0003-1010-2644
FU Intramural Research Program; NIH; NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 32
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Z9 19
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2009
VL 44
IS 2
BP 448
EP 454
DI 10.1016/j.neuroimage.2008.08.037
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KH
UT WOS:000262301100015
PM 18835582
ER
PT J
AU Smith, BW
Mitchell, DGV
Hardin, MG
Jazbec, S
Fridberg, D
Blair, RJR
Ernst, M
AF Smith, Bruce W.
Mitchell, Derek G. V.
Hardin, Michael G.
Jazbec, Sandra
Fridberg, Daniel
Blair, R. James R.
Ernst, Monique
TI Neural substrates of reward magnitude, probability, and risk during a
wheel of fortune decision-making task
SO NEUROIMAGE
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; VENTROMEDIAL PREFRONTAL
CORTEX; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; FINANCIAL REWARD;
CHOICE SELECTION; ACTIVATION; RESPONSES; AMYGDALA
AB Economic decision-making involves the weighting of magnitude and probability of potential gains/losses. While previous work has examined the neural systems involved in decision-making, there is a need to understand how the parameters associated with decision-making (e.g., magnitude of expected reward, probability of expected reward and risk) modulate activation within these neural systems. In the current fMRI study, we modified the monetary wheel of fortune (WOF) task [Ernst, M., Nelson, E. E., McClure, E. B., Monk, C.S., Munson, S., Eshel, N., et al. (2004). Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the neural responses to selections of different reward magnitudes, probabilities, or risks. Selection of high, relative to low, reward magnitude increased activity in insula, amygdala, middle and posterior cingulate cortex, and basal ganglia. Selection of low-probability, as opposed to high-probability reward, increased activity in anterior cingulate cortex, as did selection of risky, relative to safe reward. In summary, decision-making that did not involve conflict, as in the magnitude contrast, recruited structures known to support the coding of reward values, and those that integrate motivational and perceptual information for behavioral responses. In contrast, decision-making under conflict, as in the probability and risk contrasts, engaged the dorsal anterior cingulate cortex whose role in conflict monitoring is well established. However, decision-making under conflict failed to activate the structures that track reward values per se. Thus, the presence of conflict in decision-making seemed to significantly alter the pattern of neural responses to simple rewards. In addition, this paradigm further clarifies the functional specialization of the cingulate cortex in processes of decision-making. Published by Elsevier Inc.
C1 [Hardin, Michael G.; Jazbec, Sandra; Blair, R. James R.; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA.
[Smith, Bruce W.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Mitchell, Derek G. V.] Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada.
[Mitchell, Derek G. V.] Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada.
[Fridberg, Daniel] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, 15K North Dr, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
FU National Institute of Mental Health Intramural Research Program
FX This research was supported by the National Institute of Mental Health
Intramural Research Program. We wish to thank Ellen Condon for her
assistance with the data collection.
NR 63
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U1 5
U2 15
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 JAN 15
PY 2009
VL 44
IS 2
BP 600
EP 609
DI 10.1016/j.neuroimage.2008.08.016
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 392KH
UT WOS:000262301100030
PM 18804540
ER
PT J
AU Porter, BO
Anthony, KB
Shen, J
Hahn, B
Keh, CE
Maidarelli, F
Blackwelder, WC
Lane, HC
Kovacs, JA
Davey, RT
Sereti, I
AF Porter, Brian O.
Anthony, Kara B.
Shen, Jean
Hahn, Barbara
Keh, Chris E.
Maidarelli, Frank
Blackwelder, William C.
Lane, Henry Clifford
Kovacs, Joseph A.
Davey, Richard T.
Sereti, Irini
TI Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T
cell counts during HAART interruption: a randomized controlled trial
SO AIDS
LA English
DT Article
DE CD4 lymphocyte count; HAART; HIV infections; interleukin-2;
lipodystrophy; randomized controlled trial
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; ACTIVE
ANTIRETROVIRAL THERAPY; INTERMITTENT INTERLEUKIN-2 THERAPY; CHRONICALLY
HIV-1-INFECTED PATIENTS; SUBCUTANEOUS INTERLEUKIN-2; INTERNATIONAL
TRIAL; CARDIOVASCULAR RISK; TYPE-1 INFECTION; RNA LEVELS
AB Objective: To evaluate whether interleukin(IL)-2 in patients with chronic HIV infection can maintain CD4 T cell counts during 6 months of HAART interruption.
Design: Prospective, randomized, controlled, open-label phase 11 noninferiority trial comparing IL-2 with HAART interruption or continuous HAART.
Methods: Forty-one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4 cell count at least 500 cells/mu l were randomized in the ratio 2 :1 to interrupted (l=27) or continuous (C = 14) HAART for 6 months following an initial IL-2 cycle. Subsequent IL-2 cycles were triggered by CD4 T cell Counts less than 90% of baseline. Immune, metabolic, and quality of life indices were compared (Mann-Whitney and Fisher's exact tests), defining noninferiority as a percentage difference (C - l) in treatment Success (CD4 T cells >= 90% of baseline at 6 months) with a 95% confidence interval (CI) lower limit greater than -20%.
Results: Demographic and immune parameters were similar between the groups at baseline. Median CD4 T cell count, HIV viral load, and treatment success differed significantly at 6 months (l: 866cells/mu l, 39389copies/ml, 48.10%; C: 1246cells/mu l, <50 copies/ml, 92.3%; P <= 0.001). Group I was inferior to C (% difference = -44.2%; 95% Cl: -64.2%, -11.2%; P=0.013). Minor statistically significant differences in HgbA1c and energy level occurred at 6 months(l>C). Following HAART interruption, single cases of acute retroviral syndrome, secondary syphilis, non-Hodgkin's lymphoma, and Kaposi's sarcoma recurrence were observed.
Conclusion: IL-2 alone was inferior to IL-2 with HAART in maintaining baseline CD4 T cell counts. HAART interruption had a small impact on metabolic parameters and quality of life. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Porter, Brian O.; Anthony, Kara B.; Keh, Chris E.; Blackwelder, William C.; Lane, Henry Clifford; Davey, Richard T.; Sereti, Irini] NIAID, NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20982 USA.
[Shen, Jean; Hahn, Barbara] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Kovacs, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Maidarelli, Frank; Blackwelder, William C.] NCI, NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIAID, NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 11C103,10 Ctr Dr, Bethesda, MD 20982 USA.
EM isereti@niaid.nih.gov
FU National Institutes of Health (Bethesda, Maryland, USA); Novartis
(Emeryville, California, USA)
FX This work was funded through the National Institute of Allergy &
Infectious Diseases Clinical and Molecular Retrovirology Section of the
National Institutes of Health (Bethesda, Maryland, USA). Human
recombinant IL-2 was provided by Novartis (Emeryville, California, USA).
NR 62
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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 JAN 14
PY 2009
VL 23
IS 2
BP 203
EP 212
DI 10.1097/QAD.0b013e32831cc114
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 400OB
UT WOS:000262876600007
PM 19098490
ER
PT J
AU Goedert, JJ
AF Goedert, James J.
TI Nonsmoking and other cofactors for Kaposi's sarcoma
SO AIDS
LA English
DT Letter
ID RISK-FACTORS; HOMOSEXUAL-MEN; AIDS; HERPESVIRUS; CANCER
C1 NCI, Infect & Immunoepidemiol Branch, Rockville, MD 20852 USA.
RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
NR 14
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 JAN 14
PY 2009
VL 23
IS 2
BP 273
EP 274
DI 10.1097/QAD.0b013e32831f4674
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 400OB
UT WOS:000262876600019
PM 19098500
ER
PT J
AU McDermott, MM
Ades, P
Guralnik, JM
Dyer, A
Ferrucci, L
Liu, K
Nelson, M
Lloyd-Jones, D
Van Horn, L
Garside, D
Kibbe, M
Domanchuk, K
Stein, JH
Liao, YH
Tao, HM
Green, D
Pearce, WH
Schneider, JR
McPherson, D
Laing, ST
McCarthy, WJ
Shroff, A
Criqui, MH
AF McDermott, Mary M.
Ades, Philip
Guralnik, Jack M.
Dyer, Alan
Ferrucci, Luigi
Liu, Kiang
Nelson, Miriam
Lloyd-Jones, Donald
Van Horn, Linda
Garside, Daniel
Kibbe, Melina
Domanchuk, Kathryn
Stein, James H.
Liao, Yihua
Tao, Huimin
Green, David
Pearce, William H.
Schneider, Joseph R.
McPherson, David
Laing, Susan T.
McCarthy, Walter J.
Shroff, Adhir
Criqui, Michael H.
TI Treadmill Exercise and Resistance Training in Patients With Peripheral
Arterial Disease With and Without Intermittent Claudication A Randomized
Controlled Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ANKLE BRACHIAL INDEX; LOWER-EXTREMITY ISCHEMIA; PHYSICAL-ACTIVITY; LEG
SYMPTOMS; CLINICAL CHARACTERISTICS; SUBSEQUENT DISABILITY; FUNCTIONAL
IMPAIRMENT; CARDIOVASCULAR EVENTS; PERFORMANCE-MEASURES; SKELETAL-MUSCLE
AB Context Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease ( PAD) without intermittent claudication have been established as beneficial.
Objective To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication.
Design, Setting, and Participants Randomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group.
Main Outcome Measures Six- minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow- mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36- Item Short Form Health Survey physical functioning ( SF- 36 PF) score.
Results For the 6- minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m ( 95% confidence interval [ CI], 15.3- 56.5 m; P <. 001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m ( 95% CI, - 8.42 to 33.3 m; P=. 24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow- mediated dilation, those in the treadmill group had a mean improvement of 1.53% ( 95% CI, 0.35%- 2.70%; P=. 02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time ( 3.44 minutes; 95% CI, 2.05- 4.84 minutes; P <. 001); walking impairment distance score ( 10.7; 95% CI, 1.56- 19.9; P=. 02); and SF- 36 PF score ( 7.5; 95% CI, 0.00- 15.0; P=. 02) than the control group. The resistance training group had greater increases in maximal treadmill walking time ( 1.90 minutes; 95% CI, 0.49-3.31 minutes; P=. 009); walking impairment scores for distance ( 6.92; 95% CI, 1.07-12.8; P=. 02) and stair climbing ( 10.4; 95% CI, 0.00- 20.8; P=. 03); and SF- 36 PF score ( 7.5; 95% CI, 0.0- 15.0; P=. 04) than the control group.
Conclusions Supervised treadmill training improved 6- minute walk performance, treadmill walking performance, brachial artery flow- mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability.
Trial Registration clinicaltrials. gov Identifier: NCT00106327.
C1 [McDermott, Mary M.; Lloyd-Jones, Donald; Domanchuk, Kathryn; Green, David] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Dyer, Alan; Liu, Kiang; Lloyd-Jones, Donald; Van Horn, Linda; Garside, Daniel; Liao, Yihua; Tao, Huimin] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kibbe, Melina; Pearce, William H.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ades, Philip] Univ Vermont, Dept Med, Burlington, VT USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Baltimore, MD 21224 USA.
[Nelson, Miriam] Tufts Univ, Medford, MA 02155 USA.
[Stein, James H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA.
[Schneider, Joseph R.] Cent DuPage Hosp, Dept Surg, Winfield, IL USA.
[McPherson, David; Laing, Susan T.] Univ Texas Houston, Hlth Sci Ctr, Dept Med, Houston, TX USA.
[McCarthy, Walter J.] Rush Univ, Sch Med, Dept Surg, Chicago, IL 60612 USA.
[Shroff, Adhir] Univ Illinois, Dept Med, Chicago, IL USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), 750 Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
RI Lloyd-Jones, Donald/C-5899-2009
FU National Heart, Lung, and Blood Institute [R01-HL073551]; National
Center for Research Resources [RR-00048]; National Institutes of Health;
Intramural Research Program; National Institutes on Aging
FX Supported by grants R01-HL073551 from the National Heart, Lung, and
Blood Institute and by RR-00048 from the National Center for Research
Resources, National Institutes of Health. This was also supported in
part by the Intramural Research Program, National Institutes on Aging.
NR 49
TC 160
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U1 4
U2 14
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 14
PY 2009
VL 301
IS 2
BP 165
EP 174
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 393VV
UT WOS:000262405500018
PM 19141764
ER
PT J
AU Chandler, RK
Fletcher, BW
Volkow, ND
AF Chandler, Redonna K.
Fletcher, Bennett W.
Volkow, Nora D.
TI Treating Drug Abuse and Addiction in the Criminal Justice System
Improving Public Health and Safety
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; HIV-INFECTED PRISONERS;
METHADONE-MAINTENANCE; COCAINE ADDICTION; HEPATITIS-C; CORRECTIONAL
POPULATIONS; COOCCURRING DISORDERS; ORBITOFRONTAL CORTEX; NEURAL
SYSTEMS; SELF-CONTROL
AB Despite increasing evidence that addiction is a treatable disease of the brain, most individuals do not receive treatment. Involvement in the criminal justice system often results from illegal drug- seeking behavior and participation in illegal activities that reflect, in part, disrupted behavior ensuing from brain changes triggered by repeated drug use. Treating drug- involved offenders provides a unique opportunity to decrease substance abuse and reduce associated criminal behavior. Emerging neuroscience has the potential to transform traditional sanction- oriented public safety approaches by providing new therapeutic strategies against addiction that could be used in the criminal justice system. We summarize relevant neuroscientific findings and evidence- based principles of addiction treatment that, if implemented in the criminal justice system, could help improve public heath and reduce criminal behavior.
C1 [Chandler, Redonna K.; Fletcher, Bennett W.; Volkow, Nora D.] Natl Inst Drug Abuse, Serv Res Branch, Bethesda, MD 20892 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Serv Res Branch, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 82
TC 152
Z9 152
U1 8
U2 32
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 14
PY 2009
VL 301
IS 2
BP 183
EP 190
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 393VV
UT WOS:000262405500020
PM 19141766
ER
PT J
AU Driscoll, CA
Yamaguchi, N
Bar-Gal, GK
Roca, AL
Luo, SJ
Macdonald, DW
O'Brien, SJ
AF Driscoll, Carlos A.
Yamaguchi, Nobuyuki
Bar-Gal, Gila Kahila
Roca, Alfred L.
Luo, Shujin
Macdonald, David W.
O'Brien, Stephen J.
TI Mitochondrial Phylogeography Illuminates the Origin of the Extinct
Caspian Tiger and Its Relationship to the Amur Tiger
SO PLOS ONE
LA English
DT Article
AB The Caspian tiger (Panthera tigris virgata) flourished in Central Asian riverine forest systems in a range disjunct from that of other tigers, but was driven to extinction in 1970 prior to a modern molecular evaluation. For over a century naturalists puzzled over the taxonomic validity, placement, and biogeographic origin of this enigmatic animal. Using ancient-DNA (aDNA) methodology, we generated composite mtDNA haplotypes from twenty wild Caspian tigers from throughout their historic range sampled from museum collections. We found that Caspian tigers carry a major mtDNA haplotype differing by only a single nucleotide from the monomorphic haplotype found across all contemporary Amur tigers (P. t. altaica). Phylogeographic analysis with extant tiger subspecies suggests that less than 10,000 years ago the Caspian/Amur tiger ancestor colonized Central Asia via the Gansu Corridor (Silk Road) from eastern China then subsequently traversed Siberia eastward to establish the Amur tiger in the Russian Far East. The conservation implications of these findings are far reaching, as the observed genetic depletion characteristic of modern Amur tigers likely reflects these founder migrations and therefore predates human influence. Also, due to their evolutionary propinquity, living Amur tigers offer an appropriate genetic source should reintroductions to the former range of the Caspian tiger be implemented.
C1 [Driscoll, Carlos A.; Yamaguchi, Nobuyuki; Macdonald, David W.] Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Tubney, Oxon, England.
[Driscoll, Carlos A.; Luo, Shujin; O'Brien, Stephen J.] NCI, Lab Genom Diversity, Bethesda, MD 20892 USA.
[Bar-Gal, Gila Kahila] Hebrew Univ Jerusalem, Fac Agr Food & Environm Quality Sci, Koret Sch Vet Med, IL-91905 Jerusalem, Israel.
[Roca, Alfred L.] NCI Frederick, SAIC Frederick, Lab Genom Diversity, Frederick, MD USA.
[Roca, Alfred L.] Univ Illinois, Dept Animal Sci, Urbana, IL USA.
RP Driscoll, CA (reprint author), Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Tubney, Oxon, England.
EM bigscience@ncifcrf.gov; obrien@ncifcrf.gov
OI Driscoll, Carlos/0000-0003-2392-505X
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
N01-CO-12400. The contents of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 44
TC 21
Z9 25
U1 4
U2 48
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 JAN 14
PY 2009
VL 4
IS 1
AR e4125
DI 10.1371/journal.pone.0004125
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437IF
UT WOS:000265479700002
PM 19142238
ER
PT J
AU Gruschus, JM
Chen, PW
Luo, RB
Randazzo, PA
AF Gruschus, James M.
Chen, Pei-Wen
Luo, Ruibai
Randazzo, Paul A.
TI Journey to the Ends of the Arf
SO STRUCTURE
LA English
DT Editorial Material
ID NUCLEOTIDE EXCHANGE FACTOR; GTP-BINDING PROTEINS; ADP-RIBOSYLATION;
FAMILY; ARNO
AB In this issue, Liu et al. (2009) used NMR to provide the most complete information to date on the structure of Arf1 and the role of myristate in GDP/GTP exchange. Unanticipated details lead to speculation about functions for the N and C termini of Arfs.
C1 [Chen, Pei-Wen; Luo, Ruibai; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Gruschus, James M.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
RI Chen, Pei-Wen/B-7142-2015
FU Intramural NIH HHS
NR 10
TC 2
Z9 2
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD JAN 14
PY 2009
VL 17
IS 1
BP 2
EP 4
DI 10.1016/j.str.2008.12.002
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 395UT
UT WOS:000262549700002
PM 19141275
ER
PT J
AU Niu, SL
Doctrow, B
Mitchell, DC
AF Niu, Shui-Lin
Doctrow, Brian
Mitchell, Drake C.
TI Rhodopsin Activity Varies in Proteoliposomes Prepared by Different
Techniques
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; BIOLOGICAL MOLECULAR GENERATORS;
METARHODOPSIN-II; MEMBRANE-PROTEINS; ELECTRIC-CURRENT; FUNCTIONAL
RECONSTITUTION; OCTYL GLUCOSIDE; LIPOSOMES; OLIGOMERIZATION;
PURIFICATION
AB A variety of techniques are currently in use for preparing protein-containing lipid vesicles known as proteoliposomes. However, the functionality of membrane protein in proteoliposomes prepared by various techniques has rarely been evaluated directly. We prepared rhodopsin-containing proteoliposomes consisting of asolectin or native retinal rod outer segment disk lipids using n-octyl beta-D-glucopyranoside and the detergent dialysis (DD) and rapid dilution (RD) techniques and measured the activity of rhodopsin using equilibrium UV/vis and flash photolysis spectroscopy. A significant difference in rhodopsin activity was observed in proteoliposomes prepared by these techniques. The equilibrium constant of metarhodopsin I-metarhodopsin II is 30-45% higher, and the apparent rate constant of MU formation is up to 3-fold faster in proteoliposomes prepared by RD vs DD. The DD technique produced larger yet more heterogeneous vesicles, while the RD technique yielded smaller and more homogeneous vesicles, as determined by electron microscopy and isopicnic centrifugation. Both proteoliposomes and empty lipid vesicles lacking rhodopsin were formed in the DD preparation, while only proteoliposomes were formed in the RD preparation. Under identical conditions, proteoliposomes prepared by RD have a higher L/P ratio, which is consistent with the higher level of rhodopsin activity in RD proteoliposomes. Overall, the results presented here suggest that the RD technique has an advantage over the DD technique in terms of preserving optimal rhodopsin activity and controlling the lipid to protein ratio in the final proteoliposomes.
C1 [Niu, Shui-Lin; Doctrow, Brian; Mitchell, Drake C.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
RP Mitchell, DC (reprint author), Portland State Univ, Dept Phys, POB 751, Portland, OR 97207 USA.
EM drakem@pdx.edu
NR 46
TC 8
Z9 9
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JAN 13
PY 2009
VL 48
IS 1
BP 156
EP 163
DI 10.1021/bi801835s
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 391WW
UT WOS:000262265900017
PM 19090672
ER
PT J
AU Foroud, T
Sauerbeck, L
Brown, R
Anderson, C
Woo, D
Kleindorfer, D
Flaherty, ML
Deka, R
Hornung, R
Meissner, I
Bailey-Wilson, JE
Langefeld, C
Rouleau, G
Connolly, ES
Lai, DB
Koller, DL
Huston, J
Broderick, JP
AF Foroud, Tatiana
Sauerbeck, Laura
Brown, Robert
Anderson, Craig
Woo, Daniel
Kleindorfer, Dawn
Flaherty, Matthew L.
Deka, Ranian
Hornung, Richard
Meissner, Irene
Bailey-Wilson, Joan E.
Langefeld, Carl
Rouleau, Guy
Connolly, E. Sander
Lai, Dongbing
Koller, Daniel L.
Huston, John, III
Broderick, Joseph P.
CA FIA Study Investigators
TI Genome screen in familial intracranial aneurysm
SO BMC MEDICAL GENETICS
LA English
DT Article
ID ABDOMINAL AORTIC-ANEURYSM; SUBARACHNOID HEMORRHAGE; CEREBRAL ANEURYSMS;
LINKAGE DISEQUILIBRIUM; MR-ANGIOGRAPHY; HISTORY; ASSOCIATION; LOCUS;
MAPS; MARKERS
AB Background: Individuals with 1st degree relatives harboring an intracranial aneurysm (IA) are at an increased risk of IA, suggesting genetic variation is an important risk factor.
Methods: Families with multiple members having ruptured or unruptured A were recruited and all available medical records and imaging data were reviewed to classify possible A subjects as definite, probable or possible A or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of A reported to date. A 'narrow' (n = 705 definite A cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene x smoking interaction.
Results: Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene x smoking interaction was detected using both disease models on chromosome 7p (60 cM; p <= 0.01). Our study provides modest evidence of possible linkage to several chromosomes.
Conclusion: These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the A families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.
C1 [Foroud, Tatiana; Lai, Dongbing; Koller, Daniel L.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA.
[Sauerbeck, Laura; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L.; Deka, Ranian; Broderick, Joseph P.] Univ Cincinnati, Sch Med, Cincinnati, OH USA.
[Anderson, Craig] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2006, Australia.
[Brown, Robert; Meissner, Irene; Huston, John, III] Mayo Clin, Rochester, MN USA.
[Hornung, Richard] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Bailey-Wilson, Joan E.] NHGRI, Baltimore, MD USA.
[Langefeld, Carl] Wake Forest Univ Med, Winston Salem, NC USA.
[Rouleau, Guy] Univ Montreal, Ctr Excellence Neurom, Montreal, PQ, Canada.
[Connolly, E. Sander] Columbia Univ, New York, NY USA.
RP Foroud, T (reprint author), Indiana Univ, Sch Med, Indianapolis, IN 46204 USA.
EM tforoud@iupui.edu; SAUERBLR@ucmail.uc.edu; brown@mayo.edu;
canderson@george.org.au; WOODL@ucmail.uc.edu; KLEINDDO@ucmail.uc.edu;
matthew.flaherty@uc.edu; DEKAR@ucmail.uc.edu; richard.hornung@cchmc.org;
meissner.irene@mayo.edu; jebw@nhgri.nih.gov; clangefe@wfubmc.edu;
guy.rouleau@umontreal.ca; esc5@columbia.edu; dlai@iupui.edu;
dkoller@iupui.edu; jhuston@mayo.edu; broderjp@ucmail.edu
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU National Institute of Neurological Diseases and Stroke [ROI NS39512];
National Institutes of Health [NOI-HG-65403]; NHGRI
FX This study was funded by a grant from the National Institute of
Neurological Diseases and Stroke (NINDS ROI NS39512). Genotyping
services were provided by the Center for Inherited Disease Research
(CIDR). CIDR is fully funded through a federal contract from the
National Institutes of Health to The Johns Hopkins University, Contract
Number NOI-HG-65403. This research was also supported in part by the
Intramural Research Program of the NHGRI, NIH.
NR 34
TC 12
Z9 13
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JAN 13
PY 2009
VL 10
AR 3
DI 10.1186/1471-2350-10-3
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 404BI
UT WOS:000263125300002
PM 19144135
ER
PT J
AU Ruiz, MIG
Floor, K
Steinberg, SM
Grunberg, K
Thunnissen, FBJM
Belien, JAM
Meijer, GA
Peters, GJ
Smit, EF
Rodriguez, JA
Giaccone, G
AF Ruiz, M. I. Galleges
Floor, K.
Steinberg, S. M.
Grunberg, K.
Thunnissen, F. B. J. M.
Belien, J. A. M.
Meijer, G. A.
Peters, G. J.
Smit, E. F.
Rodriguez, J. A.
Giaccone, G.
TI Combined assessment of EGFR pathway-related molecular markers and
prognosis of NSCLC patients
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE EGFR pathway; NSCLC; prognosis; CMET; KRAS; biomarkers
ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; GENE COPY NUMBER; TYROSINE
KINASE INHIBITOR; IN-SITU-HYBRIDIZATION; K-RAS MUTATION; TISSUE
MICROARRAY; ONCOLOGY-GROUP; E-CADHERIN; GEFITINIB
AB The purpose of this study is to evaluate the prognostic value of the combined assessment of multiple molecular markers related to the epidermal growth factor receptor (EGFR) pathway in resected non-small cell lung cancer (NSCLC) patients. Tumour specimens of 178 NSCLC patients were collected and analysed for EGFR and KRAS mutation status by DNA sequencing, and for EGFR copy number by fluorescent in situ hybridisation. Tissue microarrays were generated and used to determine the expression of multiple EGFR pathway-related proteins by immunohistochemistry. We analysed the association between each marker and patient prognosis. Univariate analyses for each clinical variable and each molecular marker were performed using Kaplan-Meier curves and log-rank tests. From these results, we selected the variables KRAS mutations and expression of cytoplasmic EGFR, granular pERK, nuclear pSTAT3, cytoplasmic E-cadherin and cytoplasmic pCMET to enter into a Cox proportional hazards model, along with stage as the strongest clinical variable related with prognosis. Of the EGFR-related markers evaluated here, the markers EGFR, pERK, pSTAT3, E-cadherin, pCMET and mutations in KRAS were associated with survival when analysed in combination in our patient cohort, with P = 0.00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary.
C1 [Giaccone, G.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ruiz, M. I. Galleges; Floor, K.; Peters, G. J.; Rodriguez, J. A.] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, Amsterdam, Netherlands.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Grunberg, K.; Thunnissen, F. B. J. M.; Belien, J. A. M.; Meijer, G. A.] Vrije Univ Amsterdam, Dept Pathol, Med Ctr, Amsterdam, Netherlands.
[Smit, E. F.] Vrije Univ Amsterdam, Dept Pulm Dis, Med Ctr, Amsterdam, Netherlands.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Grunberg, Katrien/M-9715-2015; Giaccone, Giuseppe/E-8297-2017;
OI Grunberg, Katrien/0000-0003-1164-4365; Giaccone,
Giuseppe/0000-0002-5023-7562; Thunnissen, Erik/0000-0001-5355-8508
NR 48
TC 22
Z9 23
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JAN 13
PY 2009
VL 100
IS 1
BP 145
EP 152
DI 10.1038/sj.bjc.6604781
PG 8
WC Oncology
SC Oncology
GA 391XO
UT WOS:000262267700022
PM 19050706
ER
PT J
AU Liao, WT
Fujita, K
Xiao, Q
Tchikov, V
Yang, WS
Gunsor, M
Garfield, S
Goldsmith, P
Ei-Deiry, WS
Schutze, S
Srinivasula, SM
AF Liao, Wentao
Fujita, Ken-ichi
Xiao, Qi
Tchikov, Vladimir
Yang, Wensheng
Gunsor, Michele
Garfield, Susan
Goldsmith, Paul
Ei-Deiry, Wafik S.
Schutze, Stefan
Srinivasula, Srinivasa M.
TI Response: CARP1 regulates induction of NF-kappa B by TNF alpha
SO CURRENT BIOLOGY
LA English
DT Letter
ID UBIQUITIN LIGASE; DEFICIENT MICE; DEATH
C1 [Liao, Wentao; Fujita, Ken-ichi; Xiao, Qi; Srinivasula, Srinivasa M.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Tchikov, Vladimir; Schutze, Stefan] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany.
[Yang, Wensheng; Ei-Deiry, Wafik S.] Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, Dept Med Hematol Oncol,Inst Translat Med & Therap, Philadelphia, PA 19104 USA.
[Yang, Wensheng; Ei-Deiry, Wafik S.] Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, Dept Genet,Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Yang, Wensheng; Ei-Deiry, Wafik S.] Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, Dept Genet,Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Yang, Wensheng; Ei-Deiry, Wafik S.] Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, Dept Pharmacol,Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Yang, Wensheng; Ei-Deiry, Wafik S.] Univ Penn, Sch Med, Abramson Comprehens Canc Ctr, Philadelphia, PA 19104 USA.
[Gunsor, Michele; Goldsmith, Paul] NCI, Antibody & Prot Purificat Unit, OSTP OD CCR, NIH, Bethesda, MD 20892 USA.
[Garfield, Susan] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Liao, WT (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
EM srinivsr@mail.nih.gov
RI Schutze, Stefan/C-8596-2011; Liao, Wentao/F-7913-2011
NR 11
TC 4
Z9 6
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JAN 13
PY 2009
VL 19
IS 1
BP R17
EP R19
DI 10.1016/j.cub.2008.11.041
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 396HZ
UT WOS:000262584100010
ER
PT J
AU Resnick, SM
Espeland, MA
Jaramillo, SA
Hirsch, C
Stefanick, ML
Murray, AM
Ockene, J
Davatzikos, C
AF Resnick, S. M.
Espeland, M. A.
Jaramillo, S. A.
Hirsch, C.
Stefanick, M. L.
Murray, A. M.
Ockene, J.
Davatzikos, C.
CA Womens Hlth Initiative Memory Stud
TI Postmenopausal hormone therapy and regional brain volumes The WHIMS-MRI
Study
SO NEUROLOGY
LA English
DT Article
ID HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; RANDOMIZED
CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; MILD COGNITIVE
IMPAIRMENT; REPLACEMENT THERAPY; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE;
WOMEN; DEMENTIA
AB Objectives: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.
Methods: Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.
Results: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm3) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores + 90).
Conclusions: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy. Neurology (R) 2009; 72: 135-142
C1 [Resnick, S. M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Espeland, M. A.; Jaramillo, S. A.] Wake Forest Univ, Div Publ Hlth Sci, Sch Med, Winston Salem, NC 27109 USA.
[Hirsch, C.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA.
[Hirsch, C.] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Stefanick, M. L.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Murray, A. M.] Hennepin Cty Med Ctr, Chron Dis Res Grp, Minneapolis, MN 55415 USA.
[Ockene, J.] Univ Massachusetts, Worcester, MA 01605 USA.
[Davatzikos, C.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Intramural Res Program, NIH,Biomed Res Ctr, 04B317,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM susan.resnick@nih.gov
FU National Heart, Lung, and Blood Institute of the NIH; US Department of
Health and Human Services; Wyeth Pharmaceuticals, Inc.,
FX The Women's Health Initiative and WHIMS-MRI Study are funded by the
National Heart, Lung, and Blood Institute of the NIH, US Department of
Health and Human Services. WHIMS was funded in part by Wyeth
Pharmaceuticals, Inc., St. Davids, PA. S. M. R. is supported by the
Intramural Research Program, National Institute on Aging, NIH.
NR 40
TC 94
Z9 97
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JAN 13
PY 2009
VL 72
IS 2
BP 135
EP 142
DI 10.1212/01.wnl.0000339037.76336.cf
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 393SM
UT WOS:000262393200006
PM 19139364
ER
PT J
AU Krammer, C
Kryndushkin, D
Suhre, MH
Kremmer, E
Hofmann, A
Pfeifer, A
Scheibel, T
Wickner, RB
Schatzl, HM
Vorberg, I
AF Krammer, Carmen
Kryndushkin, Dmitry
Suhre, Michael H.
Kremmer, Elisabeth
Hofmann, Andreas
Pfeifer, Alexander
Scheibel, Thomas
Wickner, Reed B.
Schaetzl, Hermann M.
Vorberg, Ina
TI The yeast Sup35NM domain propagates as a prion in mammalian cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE PrP; Sup35
ID SACCHAROMYCES-CEREVISIAE; HET-S; PSI+ PRION; IN-VITRO; PROTEIN;
DETERMINANT; STRAINS; PSI(+); CHAPERONES; HSP104
AB Prions are infectious, self-propagating amyloid-like protein aggregates of mammals and fungi. We have studied aggregation propensities of a yeast prion domain in cell culture to gain insights into general mechanisms of prion replication in mammalian cells. Here, we report the artificial transmission of a yeast prion across a phylogenetic kingdom. HA epitope-tagged yeast Sup35p prion domain NM was stably expressed in murine neuroblastoma cells. Although cytosolically expressed NM-HA remained soluble, addition of fibrils of bacterially produced Sup35NM to the medium efficiently induced appearance of phenotypically and biochemically distinct NM- HA aggregates that were inherited by daughter cells. Importantly, NM-HA aggregates also were infectious to recipient mammalian cells expressing soluble NM-HA and, to a lesser extent, to yeast. The fact that the yeast Sup35NM domain can propagate as a prion in neuroblastoma cells strongly argues that cellular mechanisms support prion-like inheritance in the mammalian cytosol.
C1 [Krammer, Carmen; Schaetzl, Hermann M.; Vorberg, Ina] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany.
[Kryndushkin, Dmitry; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Scheibel, Thomas] Univ Bayreuth, FAN D, Lehrstuhl Biomaterialien Gebaude, D-95447 Bayreuth, Germany.
[Kremmer, Elisabeth] Helmholtz Zentrum Munchen, Inst Mol Immunol, D-81377 Munich, Germany.
[Hofmann, Andreas; Pfeifer, Alexander] Univ Bonn, Inst Pharmacol & Toxicol, D-53133 Bonn, Germany.
RP Vorberg, I (reprint author), Tech Univ Munich, Inst Virol, Trogerstr 30, D-81675 Munich, Germany.
EM vorberg@virologie.med.tum.de
RI Schatzl, Hermann/G-4958-2011; Suhre, Michael/C-5145-2009; Scheibel,
Thomas/I-1170-2014
OI Suhre, Michael/0000-0002-2279-7765; Scheibel, Thomas/0000-0002-0457-2423
FU Deutsche Forschungsgemeinschaft [SFB 596 B14, VO 1277/1-2]; European
Commission [LSHB-CT-2005-018805]; European Union NoE Neuroprion;
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health; Fonds der Chemischen Industrie
FX We thank members of the Vorberg and Schatzl laboratories for
constructive comments on this work and D. Vorberg for help with
statistics. Financial support for this work was provided by the Deutsche
Forschungsgemeinschaft SFB 596 B14, VO 1277/1-2, the European Commission
(Grant TSEUR LSHB-CT-2005-018805), the European Union NoE Neuroprion,
and in part by the Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases of the National Institutes of
Health. M. H. S. was supported by a scholarship of the Fonds der
Chemischen Industrie.
NR 42
TC 32
Z9 33
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 13
PY 2009
VL 106
IS 2
BP 462
EP 467
DI 10.1073/pnas.0811571106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399MM
UT WOS:000262804000021
PM 19114662
ER
PT J
AU Li, W
Kotoshiba, S
Berthet, C
Hilton, MB
Kaldis, P
AF Li, Weimin
Kotoshiba, Shuhei
Berthet, Cyril
Hilton, Mary Beth
Kaldis, Philipp
TI Rb/Cdk2/Cdk4 triple mutant mice elicit an alternative mechanism for
regulation of the G(1)/S transition
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell cycle; p27; retinoblastoma protein; Skp2
ID RETINOBLASTOMA GENE FAMILY; CYCLIN-DEPENDENT KINASES; CELL-CYCLE;
TARGETED DISRUPTION; EMBRYONIC LETHALITY; CDK INHIBITORS; RB; P27(KIP1);
LACKING; GROWTH
AB The G(1)/S-phase transition is a well-toned switch in the mammalian cell cycle. Cdk2, Cdk4, and the rate-limiting tumor suppressor retinoblastoma protein (Rb) have been studied in separate animal models, but interactions between the kinases and Rb in vivo have yet to be investigated. To further dissect the regulation of the G(1) to S-phase progression, we generated Cdk2(-/-)Cdk4(-/-)Rb(-/-) (TKO) mutant mice. TKO mice died at midgestation with major defects in the circulatory systems and displayed combined phenotypes of Rb-/- and Cdk2(-/-)Cdk4(-/-) mutants. However, TKO mouse embryonic fibroblasts were not only resistant to senescence and became immortal but displayed enhanced S-phase entry and proliferation rates similar to wild type. These effects were more remarkable in hypoxic compared with normoxic conditions. Interestingly, depletion of the pocket proteins by HPV-E7 or p107/p130 shRNA in the absence of Cdk2/Cdk4 elicited a mechanism for the G(1)/S regulation with increased levels of p27(Kip1) binding to Cdk1/cyclin E complexes. Our work indicates that the G(1)/S transition can be controlled in different ways depending on the situation, resembling a regulatory network.
C1 [Li, Weimin; Kotoshiba, Shuhei; Berthet, Cyril; Hilton, Mary Beth; Kaldis, Philipp] Natl Canc Inst, Mouse Canc Genet Program, Canc Res Ctr, Frederick, MD 21702 USA.
[Kotoshiba, Shuhei; Kaldis, Philipp] Natl Univ Singapore, Inst Mol & Cell Biol, Cell Div & Canc Lab, Singapore 138673, Singapore.
RP Kaldis, P (reprint author), Natl Canc Inst, Mouse Canc Genet Program, Canc Res Ctr, Bldg 560-22-56,1050 Boyles St, Frederick, MD 21702 USA.
EM kaldis@imcb.a-star.edu.sg
RI Kaldis, Philipp/G-2714-2010; ASTAR, IMCB/E-2320-2012
OI Kaldis, Philipp/0000-0002-7247-7591;
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; A* STAR of Singapore
FX We thank Matt McCollum and Angie Smith for animal care; Anton Berns for
the Rbflox/flox mice; Keith Rogers, Donna Butcher, Roberta
Smith, and the Pathology/Histotechnology Laboratory, National Cancer
Institute for tissue sectioning and staining; Jerrold Ward for the
placenta pathology; Stephen J. Lockett for helping with confocal
microscopy; Julien Sage (Stanford University, Stanford, CA) for shRNA
vectors for p107/p130; members of P. K.'s laboratory for discussions and
support; and Stefan Lim, Shuhui Lim, and Kasim Diril for comments on the
manuscript. This work was supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research, and A* STAR of Singapore.
NR 42
TC 23
Z9 28
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 13
PY 2009
VL 106
IS 2
BP 486
EP 491
DI 10.1073/pnas.0804177106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399MM
UT WOS:000262804000025
PM 19129496
ER
PT J
AU Merrikh, H
Ferrazzoli, AE
Bougdour, A
Olivier-Mason, A
Lovett, ST
AF Merrikh, Houra
Ferrazzoli, Alexander E.
Bougdour, Alexandre
Olivier-Mason, Anique
Lovett, Susan T.
TI A DNA damage response in Escherichia coli involving the alternative
sigma factor, RpoS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oxidative stress; posttranslational regulation; replication stress; SOS
response; DNA repair
ID GENE-EXPRESSION; RNA-POLYMERASE; HYDROGEN-PEROXIDE; EXONUCLEASE-III;
REGULATOR RSSB; STABILITY; REGULON; IDENTIFICATION; PATHWAYS; SUBUNIT
AB We isolated an Escherichia coli mutant in the iraD gene, sensitive to various forms of DNA damage. Our data are consistent with the function of IraD to promote accumulation of the alternative transcription sigma factor, RpoS, by binding to the adaptor RssB protein that targets RpoS for degradation. Our results demonstrate the physiological importance of this mode of regulation for DNA damage tolerance. Although RpoS is best known for its regulation of genes induced in stationary phase, our work underscores the importance of the RpoS regulon in a DNA damage response in actively growing cells. We show that iraD transcription is induced by DNA damage by a mechanism independent of the SOS response. The IraD and SOS regulatory pathways appear to act synergistically to ensure survival of cells faced with oxidative or DNA damaging stress during cellular growth.
C1 [Merrikh, Houra; Ferrazzoli, Alexander E.; Olivier-Mason, Anique; Lovett, Susan T.] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
[Merrikh, Houra; Ferrazzoli, Alexander E.; Olivier-Mason, Anique; Lovett, Susan T.] Brandeis Univ, Rosenstiel Basic Med Sci Ctr, Waltham, MA 02254 USA.
[Bougdour, Alexandre] Natl Canc Inst, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lovett, ST (reprint author), Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
EM lovett@brandeis.edu
RI Bougdour, Alexandre/K-3795-2014;
OI Bougdour, Alexandre/0000-0002-5895-0020; Lovett,
Susan/0000-0003-2792-1857
FU General Medical Sciences Institute of the National Institutes of Health
(NIH) [GM051753]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX We are indebted to Susan Gottesman for strains, reagents, and helpful
discussions. We also thank Hirotada Mori, Barry Wanner, and Malcolm
Winkler for strains. This work was supported by Grant GM051753 from the
General Medical Sciences Institute of the National Institutes of Health
(NIH) (to STL) and, in part, by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (A. B.).
NR 38
TC 37
Z9 37
U1 0
U2 11
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 JAN 13
PY 2009
VL 106
IS 2
BP 611
EP 616
DI 10.1073/pnas.0803665106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399MM
UT WOS:000262804000047
PM 19124769
ER
PT J
AU Dreher, JC
Kohn, P
Kolachana, B
Weinberger, DR
Berman, KF
AF Dreher, Jean-Claude
Kohn, Philip
Kolachana, Bhaskar
Weinberger, Daniel R.
Berman, Karen Faith
TI Variation in dopamine genes influences responsivity of the human reward
system
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE COMT; DAT; fMRI; genetic variation
ID CATECHOL-O-METHYLTRANSFERASE; OBSESSIVE-COMPULSIVE DISORDER;
MESSENGER-RNA EXPRESSION; COMT VAL(108/158) MET; PREFRONTAL CORTEX;
VAL(158)MET GENOTYPE; TRANSPORTER AVAILABILITY; BIPOLAR DISORDER; HUMAN
BRAIN; POLYMORPHISM
AB In humans, dopamine neurotransmission is influenced by functional polymorphisms in the dopamine transporter (DAT1) and catechol-O-methyltransferase (COMT) genes. Here, we used event-related functional magnetic resonance imaging to directly investigate the neurofunctional effects of the Val(158)Met COMT and variable number of tandem repeat DAT1 polymorphisms on distinct components of the reward system in humans. The results revealed a main effect of COMT genotype in the ventral striatum and lateral prefrontal cortex during reward anticipation (P < 0.001, uncorrected) and in the orbitofrontal cortex at the time of reward delivery (P < 0.005), met/met individuals exhibiting the highest activation. The main effect of DAT1 genotype was seen in robust blood-oxygen-level-dependent response differences in the caudate nucleus and ventral striatum during reward anticipation (P < 0.001) and in the lateral prefrontal cortex and midbrain at the time of reward delivery, with carriers of the DAT1 9-repeat allele showing the highest activity. Moreover, an interaction between the COMT and DAT1 genes was found in the ventral striatum and lateral prefrontal cortex during reward anticipation and in the lateral prefrontal and orbitofrontal cortices as well as in the midbrain at the time of reward delivery, with carriers of the DAT1 9-repeat allele and COMT met/met allele exhibiting the highest activation, presumably reflecting functional change consequent to higher synaptic dopamine availability. Taken together, these results indicate that genetically influenced variations in dopamine transmission modulate the response of brain regions involved in anticipation and reception of rewards and suggest that these responses may contribute to individual differences in reward-seeking behavior and in predisposition to neuropsychiatric disorders.
C1 [Dreher, Jean-Claude; Kohn, Philip; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA.
[Kohn, Philip; Kolachana, Bhaskar; Weinberger, Daniel R.; Berman, Karen Faith] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
RP Dreher, JC (reprint author), Univ Lyon 1, CNRS, Cognit Neurosci Ctr, Reward & decis Making Team, F-69365 Lyon, France.
EM dreher@isc.cnrs.fr; bermank@mail.nih.gov
NR 44
TC 189
Z9 195
U1 0
U2 10
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 JAN 13
PY 2009
VL 106
IS 2
BP 617
EP 622
DI 10.1073/pnas.0805517106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 399MM
UT WOS:000262804000048
PM 19104049
ER
PT J
AU Yang, YZ
AF Yang, Yingzi
TI Growth and Patterning in the Limb: Signaling Gradients Make the Decision
SO SCIENCE SIGNALING
LA English
DT Article
ID APICAL ECTODERMAL RIDGE; VERTEBRATE LIMB; HIND-LIMB; IN-VITRO; BUD;
CHONDROGENESIS; WNT; DIFFERENTIATION; MORPHOGENESIS; MUSCULATURE
AB The vertebrate limb bud provides a unique system to investigate the coordinated regulation of growth and patterning, two key processes that govern the formation of a complex multicellular organism from a fertilized egg. Two studies have advanced our understanding of limb development by elucidating that signaling gradients from the limb ecotoderm, including the apical ectoderm ridge (AER), act in concert to establish a basic pattern of tissue layers by coordinating cell proliferation and cell fate determination. These studies reveal that cell proliferation and fate determination in development can be two faces of the same coin in that they are regulated by the same signaling pathways. Alterations in the duration and range of the signaling gradients may underlie many of the morphological differences in the evolution of vertebrate limbs.
C1 NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA.
RP Yang, YZ (reprint author), NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bldg 49,Room 4A68,49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
NR 33
TC 13
Z9 13
U1 1
U2 11
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 JAN 13
PY 2009
VL 2
IS 53
AR pe3
DI 10.1126/scisignal.253pe3
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 567UE
UT WOS:000275471300002
PM 19141858
ER
PT J
AU Cook, NR
Obarzanek, E
Cutler, JA
Buring, JE
Rexrode, KM
Kumanyika, SK
Appel, LJ
Whelton, PK
AF Cook, Nancy R.
Obarzanek, Eva
Cutler, Jeffrey A.
Buring, Julie E.
Rexrode, Kathryn M.
Kumanyika, Shiriki K.
Appel, Lawrence J.
Whelton, Paul K.
CA Trials Hypertension Prevention Col
TI Joint Effects of Sodium and Potassium Intake on Subsequent
Cardiovascular Disease The Trials of Hypertension Prevention Follow-up
Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID URINARY ALBUMIN EXCRETION; LOWER BLOOD-PRESSURE; DIETARY POTASSIUM; SALT
REDUCTION; ELECTROLYTE EXCRETION; OBSERVATIONAL DATA; RANDOMIZED-TRIALS;
MEASUREMENT ERROR; NATIONAL-HEALTH; JAPANESE MEN
AB Background: Previous studies of dose-response effects of usual sodium and potassium intake on subsequent cardiovascular disease (CVD) have largely relied on suboptimal measures of intake.
Methods: Two trials of sodium reduction and other interventions collected 24-hour urinary excretions intermittently during 18 months from September 17, 1987, to January 12, 1990 (Trials of Hypertension Prevention [TOHP] I), and during 36 months from December 18, 1990, to April 7, 1995 (TOHP II), among adults with pre-hypertension aged 30 to 54 years. Among adults not assigned to an active sodium reduction intervention, we assessed the relationship of a mean of 3 to 7 twenty-four hour urinary excretions of sodium and potassium and their ratio with subsequent CVD (stroke, myocardial infarction, coronary revascularization, or CVD mortality) through 10 to 15 years of posttrial follow-up.
Results: Among 2974 participants, follow-up information was obtained on 2275 participants (76.5%), with 193 CVD events. After adjustment for baseline variables and lifestyle changes, there was a nonsignificant trend in CVD risk across sex-specific quartiles of urinary sodium excretion (rate ratio [RR] from lowest to highest, 1.00, 0.99, 1.16, and 1.20; P=.38 for trend) and potassium excretion (RR, 1.00, 0.94, 0.91, and 0.64; P=.08 for trend) but a significant trend across quartiles of the sodium to potassium excretion ratio (RR, 1.00, 0.84, 1.18, and 1.50; P=.04 for trend). In models containing both measures simultaneously, linear effects were as follows: RR, 1.42; 95% confidence interval (CI), 0.99 to 2.04 per 100 mmol/24 h of urinary sodium excretion (P=.05); and 0.67; 0.41 to 1.10 per 50 mmol/24 h of urinary potassium excretion (P=.12). A model containing the sodium to potassium excretion ratio (RR, 1.24; 95% CI, 1.05-1.46; P=.01) had the lowest Bayes information criterion (best fit).
Conclusion: A higher sodium to potassium excretion ratio is associated with increased risk of subsequent CVD, with an effect stronger than that of sodium or potassium alone.
C1 [Cook, Nancy R.; Buring, Julie E.; Rexrode, Kathryn M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Obarzanek, Eva; Cutler, Jeffrey A.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Appel, Lawrence J.] Johns Hopkins Univ, Dept Med, Johns Hopkins Sch Med, Baltimore, MD USA.
[Kumanyika, Shiriki K.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Loyola Univ Hlth Syst, Maywood, IL 60153 USA.
RP Cook, NR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM ncook@rics.bwh.harvard.edu
OI Rexrode, Kathryn/0000-0003-3387-8429
FU National Heart, Lung, and Blood Institute [HL37849, HL37852, HL37853,
HL37854, HL37872, HL37884, HL37899, HL37904, HL37906, HL37907, HL37924,
HL57915]; National Institutes of Health
FX TOHP I and II were supported by cooperative agreements HL37849, HL37852,
HL37853, HL37854, HL37872, HL37884, HL37899, HL37904, HL37906, HL37907,
and HL37924, and the TOHP Follow-up Study was supported by grant
HL57915, all from the National Heart, Lung, and Blood Institute,
National Institutes of Health.
NR 56
TC 150
Z9 153
U1 1
U2 21
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 JAN 12
PY 2009
VL 169
IS 1
BP 32
EP 40
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 393UL
UT WOS:000262398800004
PM 19139321
ER
PT J
AU Hindorff, LA
Burke, W
Laberge, AM
Rice, KM
Lumley, T
Leppig, K
Rosendaal, FR
Larson, EB
Psaty, BM
AF Hindorff, Lucia A.
Burke, Wylie
Laberge, Anne-Marie
Rice, Kenneth M.
Lumley, Thomas
Leppig, Kathleen
Rosendaal, Frits R.
Larson, Eric B.
Psaty, Bruce M.
TI Motivating Factors for Physician Ordering of Factor V Leiden Genetic
Tests
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID OF-THE-LITERATURE; VENOUS THROMBOEMBOLISM; MYOCARDIAL-INFARCTION;
PRIMARY-CARE; THROMBOPHILIA; RISK; GUIDELINES; SERVICES; STROKE
AB Background: The factor V Leiden (FVL) genetic test is used by many physicians despite its uncertain clinical utility.
Methods: We investigate whether self-reported motivations and behaviors concerning FVL genetic testing differ between 2 groups of primary care physicians defined by frequency of previous FVL test use. In January 2007, 112 physicians (60 frequent and 52 infrequent FVL test users) at Group Health, a large health care delivery system, were surveyed. Survey content areas included primary reasons and motivating factors for ordering the FVL test, the likelihood of ordering the FVL test for hypothetical patients, potential barriers to genetic testing, and practices and skills regarding FVL test ordering.
Results: Responses between groups agreed concerning most clinical- and patient-related factors. Frequent-FVL physicians were more likely than infrequent-FVL physicians to report ordering the FVL test for hypothetical patients with mesenteric venous thrombosis (adjusted odds ratio, 4.57; 95% confidence interval, 1.55-13.53) or venous thrombosis after hospital discharge (adjusted odds ratio, 3.42; 95% confidence interval, 1.30-8.95). Frequent-FVL physicians were also less likely to identify several items on the survey as barriers to genetic testing and were more likely to report high confidence in interpreting and explaining FVL test results.
Conclusions: Generally, both physician groups reported similar motivating factors for ordering FVL tests, and reported behaviors were consistent with existing guidelines. More striking differences were observed for measures such as barriers to and confidence in using genetic tests. Although additional research is necessary to evaluate the impact of these results, they inform several knowledge-to-practice translation issues that are important for the successful integration of genetic testing into primary care.
C1 [Hindorff, Lucia A.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Burke, Wylie] Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA.
[Rice, Kenneth M.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Laberge, Anne-Marie] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA.
[Larson, Eric B.; Psaty, Bruce M.] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA.
[Rosendaal, Frits R.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
RP Hindorff, LA (reprint author), NHGRI, NIH, 5635 Fishers Ln,Ste 4076, Bethesda, MD 20892 USA.
EM hindorffl@mail.nih.gov
RI Rice, Kenneth/A-4150-2013
OI Rice, Kenneth/0000-0001-5779-4495
FU National Heart, Lung, and Blood Institute [T32 HL07902]; Leducq
Foundation
FX This study was supported by grant T32 HL07902 from the National Heart,
Lung, and Blood Institute and by the Leducq Foundation for the
development of Transatlantic Networks of Excellence in Cardiovascular
Research.
NR 19
TC 11
Z9 11
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
EI 1538-3679
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JAN 12
PY 2009
VL 169
IS 1
BP 68
EP 74
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 393UL
UT WOS:000262398800009
PM 19139326
ER
PT J
AU Mejat, A
Decostre, V
Li, J
Renou, L
Kesari, A
Hantai, D
Stewart, CL
Xiao, X
Hoffman, E
Bonne, G
Misteli, T
AF Mejat, Alexandre
Decostre, Valerie
Li, Juan
Renou, Laure
Kesari, Akanchha
Hantai, Daniel
Stewart, Colin L.
Xiao, Xiao
Hoffman, Eric
Bonne, Gisele
Misteli, Tom
TI Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss
muscular dystrophy
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID NUCLEAR-ENVELOPE INTEGRITY; CHAIN MESSENGER-RNA; ACETYLCHOLINE-RECEPTOR;
SKELETAL-MUSCLE; GENE-EXPRESSION; PROTEIN ISOFORMS; MEMBRANE PROTEIN;
MYOD PATHWAYS; SYNE PROTEINS; SOLEUS MUSCLE
AB he LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by which mutations in LMNA cause disease have been elusive. Here, we demonstrate that defects in neuromuscular junctions (NMJs) are part of the disease mechanism in AD-EDMD. Two AD-EDMD mouse models show innervation defects including misexpression of electrical activity dependent genes and altered epigenetic chromatin modi. cations. Synaptic nuclei are not properly recruited to the NMJ because of mislocalization of nuclear envelope components. AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-EDMD mouse models. These results suggest that lamin A/C mediated NMJ defects contribute to the AD-EDMD disease phenotype and provide insights into the cellular and molecular mechanisms for the muscle-specific phenotype of AD-EDMD.
C1 [Mejat, Alexandre; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Decostre, Valerie; Renou, Laure; Hantai, Daniel; Bonne, Gisele] Inst Myol, Inst Natl Sante & Rech Med, UMR U582, F-75013 Paris, France.
[Decostre, Valerie; Hantai, Daniel; Bonne, Gisele] Univ Paris 06, Inst Federatif Rech 14, UMR S582, F-75013 Paris, France.
[Li, Juan; Xiao, Xiao] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
[Kesari, Akanchha; Hoffman, Eric] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Stewart, Colin L.] Inst Med Biol, Singapore 138668, Singapore.
[Bonne, Gisele] Grp Hosp Pitie Salpetriere, AP HP, Unite Fonctionnelle Cardiogenet & Myogenet, Serv Biochim Metab, F-75013 Paris, France.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
RI MEJAT, Alexandre/G-8635-2013; Bonne, Gisele/G-3121-2013
FU National Institutes of Health (NIH); NCI; Center for Cancer Research;
Institut National de la Santet de la Recherche Medicale (INSERM);
Assistance Publique-Hopitaux de Paris; Association Francaise contreles
Myopathies (AFM); European Union Fifth Framework [018690]; Association
Francaise contre les Myopathies (AFM) [10722]
FX Fluorescence imaging was in part done at the National Cancer Institute
(NCI) Fluorescence Imaging Facility. This research was supported by the
Intramural Research Program of the National Institutes of Health (NIH),
NCI, and Center for Cancer Research; the Institut National de la Santet
de la Recherche Medicale (INSERM), Assistance Publique-Hopitaux de
Paris, Association Francaise contreles Myopathies (AFM), the European
Union Fifth Framework (Euro-laminopathies contract No. 018690), and the
Association Francaise contre les Myopathies (AFM) rare disorder network
program (10722).
NR 60
TC 61
Z9 63
U1 1
U2 9
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JAN 12
PY 2009
VL 184
IS 1
BP 31
EP 44
DI 10.1083/jcb.200811035
PG 14
WC Cell Biology
SC Cell Biology
GA 400KR
UT WOS:000262867000006
PM 19124654
ER
PT J
AU Xu, R
Nelson, CM
Muschler, JL
Veiseh, M
Vonderhaar, BK
Bissell, MJ
AF Xu, Ren
Nelson, Celeste M.
Muschler, John L.
Veiseh, Mandana
Vonderhaar, Barbara K.
Bissell, Mina J.
TI Sustained activation of STAT5 is essential for chromatin remodeling and
maintenance of mammary-specific function
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID PROTEIN GENE-EXPRESSION; RECONSTITUTED BASEMENT-MEMBRANE; GROWTH-FACTOR
RECEPTOR; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; TYROSINE
PHOSPHORYLATION; TRANSCRIPTION FACTORS; IN-VIVO; PROLACTIN; CASEIN
AB Epithelial cells, once dissociated and placed in two-dimensional (2D) cultures, rapidly lose tissue-specific functions. We showed previously that in addition to prolactin, signaling by laminin-111 was necessary to restore functional differentiation of mammary epithelia. Here, we elucidate two additional aspects of laminin-111 action. We show that in 2D cultures, the prolactin receptor is basolaterally localized and physically segregated from its apically placed ligand. Detachment of the cells exposes the receptor to ligation by prolactin leading to signal transducers and activators of transcription protein 5 (STAT5) activation, but only transiently and not sufficiently for induction of milk protein expression. We show that laminin-111 reorganizes mammary cells into polarized acini, allowing both the exposure of the prolactin receptor and sustained activation of STAT5. The use of constitutively active STAT5 constructs showed that the latter is necessary and sufficient for chromatin reorganization and beta-casein transcription. These results underscore the crucial role of continuous laminin signaling and polarized tissue architecture in maintenance of transcription factor activation, chromatin organization, and tissue-specific gene expression.
C1 [Xu, Ren; Nelson, Celeste M.; Veiseh, Mandana; Bissell, Mina J.] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Nelson, Celeste M.] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA.
[Muschler, John L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
[Vonderhaar, Barbara K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bissell, MJ (reprint author), Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
EM RXu@lbl.gov; MJBissell@lbl.gov
FU Office of Biological and Environmental Research (OBER) of the Department
of Energy [DOE-AC03-76SF00098]; National Institutes of Health
[R01CA057621]; National Cancer Institute [5R01CA64786]; Department of
Defense; DOD BCRP [DAMD17-02-1-0441, W81XWH-04-1-0582]; Burroughs
Wellcome Fund
FX This work was supported by the Office of Biological and Environmental
Research (OBER) of the Department of Energy (DOE; DOE-AC03-76SF00098),
the National Institutes of Health (R01CA057621) to Z. Werb and M. J.
Bissell, the National Cancer Institute (5R01CA64786) to M. J. Bissell,
and the Breast Cancer Research Program (BCRP) of the Department of
Defense (DOD; Innovator Award) to M. J. Bissell. M. J. Bissell is a
Distinguished Scientist of the OBER of the DOE. Support was also
provided by DOD BCRP postdoctoral fellowships DAMD17-02-1-0441 and
W81XWH-04-1-0582 to R. Xu and C. M. Nelson. C. M. Nelson holds a Career
Award at the Scientific Interface from the Burroughs Wellcome Fund.
NR 54
TC 68
Z9 70
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JAN 12
PY 2009
VL 184
IS 1
BP 57
EP 66
DI 10.1083/jcb.200807021
PG 10
WC Cell Biology
SC Cell Biology
GA 400KR
UT WOS:000262867000008
PM 19139262
ER
PT J
AU Wang, X
Rao, RP
Kosakowska-Cholody, T
Masood, MA
Southon, E
Zhang, HL
Berthet, C
Nagashim, K
Veenstra, TK
Tessarollo, L
Acharya, U
Acharya, JK
AF Wang, Xin
Rao, Raghavendra Pralhada
Kosakowska-Cholody, Teresa
Masood, M. Athar
Southon, Eileen
Zhang, Helin
Berthet, Cyril
Nagashim, Kunio
Veenstra, Timothy K.
Tessarollo, Lino
Acharya, Usha
Acharya, Jairaj K.
TI Mitochondrial degeneration and not apoptosis is the primary cause of
embryonic lethality in ceramide transfer protein mutant mice
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; ENDOPLASMIC-RETICULUM STRESS;
RAT-LIVER; SPHINGOLIPID BIOSYNTHESIS; DROSOPHILA-MELANOGASTER; MOLECULAR
MACHINERY; PROAPOPTOTIC BAX; OXIDATIVE STRESS; STEM-CELLS; LIFE-SPAN
AB Ceramide transfer protein (CERT) functions in the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi. In this study, we show that CERT is an essential gene for mouse development and embryonic survival and, quite strikingly, is critical for mitochondrial integrity. CERT mutant embryos accumulate ceramide in the ER but also mislocalize ceramide to the mitochondria, compromising their function. Cells in mutant embryos show abnormal dilation of the ER and degenerating mitochondria. These subcellular changes manifest as heart defects and cause severely compromised cardiac function and embryonic death around embryonic day 11.5. In spite of ceramide accumulation, CERT mutant mice do not die as a result of enhanced apoptosis. Instead, cell proliferation is impaired, and expression levels of cell cycle-associated proteins are altered. Individual cells survive, perhaps because cell survival mechanisms are activated. Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways.
C1 [Wang, Xin; Rao, Raghavendra Pralhada; Kosakowska-Cholody, Teresa; Acharya, Jairaj K.] Sci Applicat Int Corp Frederick Inc, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Masood, M. Athar; Veenstra, Timothy K.] Sci Applicat Int Corp Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA.
[Nagashim, Kunio] Sci Applicat Int Corp Frederick Inc, Electron Microscopy Facil, Frederick, MD 21702 USA.
[Southon, Eileen; Berthet, Cyril; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Zhang, Helin] Univ Maryland, Sch Med, Marlene Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Acharya, Usha] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
RP Acharya, JK (reprint author), Sci Applicat Int Corp Frederick Inc, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM acharyaj@ncifcrf.gov
FU Intramural Research Program of the National Cancer Institute; National
Institutes of Health; Department of Health and Human Services; National
Institutes of Health [R01EY16469]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, and Department
of Health and Human Services. U. Acharya is supported by a grant from
the National Institutes of Health (R01EY16469).
NR 67
TC 50
Z9 50
U1 1
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JAN 12
PY 2009
VL 184
IS 1
BP 143
EP 158
DI 10.1083/jcb.200807176
PG 16
WC Cell Biology
SC Cell Biology
GA 400KR
UT WOS:000262867000014
PM 19139267
ER
PT J
AU Nadjar, A
Gerfen, CR
Bezard, E
AF Nadjar, Agnes
Gerfen, Charles R.
Bezard, Erwan
TI Priming for L-dopa-induced dyskinesia in Parkinson's disease: A feature
inherent to the treatment or the disease?
SO PROGRESS IN NEUROBIOLOGY
LA English
DT Review
DE Parkinson's disease; Dyskinesia; Sensitization; Dopamine; Behaviour;
PKA-dependent signalling cascade; Ras-ERK pathway; 6-OHDA; Immediate
early genes; MPTP
ID LEVODOPA-INDUCED DYSKINESIA; CONTINUOUS DOPAMINERGIC STIMULATION;
6-HYDROXYDOPAMINE LESIONED RATS; ABNORMAL INVOLUNTARY MOVEMENTS;
MPTP-INDUCED PARKINSONISM; TONICALLY ACTIVE NEURONS; ELEMENT-BINDING
PROTEIN; RECEPTOR MESSENGER-RNA; C-FOS EXPRESSION; STRIATAL DOPAMINE
AB Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease ultimately experienced by the vast majority of patients. This article does not review the increased understanding of dyskinesia pathophysiology we have seen during the past few years but, instead, specifically focuses upon the very first molecular events thought to be responsible for the establishment of dyskinesia and generally grouped under the term of "priming". Priming is classically defined as the process by which the brain becomes sensitized such that administration of a dopaminergic therapy modifies the response to subsequent dopaminergic treatments. In this way, over time, with repeated treatment, the chance of dopaminergic stimulation eliciting dyskinesia is increased and once dyskinesia has been established, the severity of dyskinesia increases. In this opinion review, however, we aim at strongly opposing the common view of priming. We propose, and hopefully will demonstrate, that priming does not exist per se but is the direct and intrinsic consequence of the loss of dopamine innervation of the striatum (and other target structures), meaning that the first injections of dopaminergic drugs only exacerbate those mechanisms (sensitization) but do not induce them. Chronicity and pulsatility of subsequent dopaminergic treatment only exacerbates the likelihood of developing dyskinesia. (C) 2008 Elsevier Ltd All rights reserved.
C1 [Nadjar, Agnes; Bezard, Erwan] Univ Bordeaux 2, CNRS, Bordeaux Inst Neurosci, UMR 5227, F-33076 Bordeaux, France.
[Gerfen, Charles R.] NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA.
RP Bezard, E (reprint author), Univ Bordeaux 2, CNRS, Bordeaux Inst Neurosci, UMR 5227, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM Erwan.bezard@u-bordeaux2.fr
RI Nadjar, Agnes/D-3694-2011;
OI Bezard, Erwan/0000-0002-0410-4638
FU Intramural NIH HHS [Z01 MH002497-19, Z99 MH999999, Z01 MH002497-18, ZIA
MH002497-20]
NR 114
TC 55
Z9 59
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0301-0082
J9 PROG NEUROBIOL
JI Prog. Neurobiol.
PD JAN 12
PY 2009
VL 87
IS 1
BP 1
EP 9
DI 10.1016/j.pneurobio.2008.09.013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 406RL
UT WOS:000263312500001
PM 18938208
ER
PT J
AU Srivastava, V
AF Srivastava, Vibhuti
TI Looking East: familial support as a crucial predictor of treatment
management in psychiatric illnesses?
SO CURRENT SCIENCE
LA English
DT Letter
C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
RP Srivastava, V (reprint author), NIAAA, Neurogenet Lab, NIH, 3S-32 MSC 9412,5625 Fishers Ln, Rockville, MD 20852 USA.
EM vibhutisrivastava@yahoo.com
NR 3
TC 0
Z9 0
U1 0
U2 1
PU INDIAN ACAD SCIENCES
PI BANGALORE
PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA
SN 0011-3891
J9 CURR SCI INDIA
JI Curr. Sci.
PD JAN 10
PY 2009
VL 96
IS 1
BP 10
EP 11
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 408KB
UT WOS:000263432800007
ER
PT J
AU Boulton, AJM
Jeffcoate, WJ
Jones, TLZ
Ulbrecht, JS
AF Boulton, Andrew J. M.
Jeffcoate, William J.
Jones, Teresa L. Z.
Ulbrecht, Jon S.
TI International collaborative research on Charcot's disease
SO LANCET
LA English
DT Editorial Material
C1 [Jeffcoate, William J.] Nottingham Univ Hosp Trust, Foot Ulcer Trials Unit, Dept Diabet & Endocrinol, Nottingham NG5 1PB, England.
[Boulton, Andrew J. M.] Manchester Royal Infirm, Dept Med, Manchester M13 9WL, Lancs, England.
[Jones, Teresa L. Z.] NIDDK, DEM, NIH, Bethesda, MD USA.
[Ulbrecht, Jon S.] Penn State Univ, Penn State Inst Diabet & Obes, University Pk, PA 16802 USA.
RP Jeffcoate, WJ (reprint author), Nottingham Univ Hosp Trust, Foot Ulcer Trials Unit, Dept Diabet & Endocrinol, City Hosp Campus, Nottingham NG5 1PB, England.
EM william.jeffcoate@tiscali.co.uk
NR 1
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JAN 10
PY 2009
VL 373
IS 9658
BP 105
EP 106
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 392ZO
UT WOS:000262340900009
PM 19135599
ER
PT J
AU Scharenberg, C
Mannowetz, N
Robey, RW
Brendel, C
Repges, P
Sahrhage, T
Jahn, T
Wennemuth, G
AF Scharenberg, Christian
Mannowetz, Nadja
Robey, Robert W.
Brendel, Cornelia
Repges, Philip
Sahrhage, Tim
Jaehn, Thomas
Wennemuth, Gunther
TI ABCG2 is expressed in late spermatogenesis and is associated with the
acrosome
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE ABCG2; Spermatozoa; Acrosome; Cholesterol efflux
ID RESISTANCE-ASSOCIATED PROTEIN; MOUSE SPERMATOZOA; STEM-CELLS; SPERM;
CAPACITATION; TRANSPORTER; EFFLUX; GENE
AB An increasingly exploited strategy for the isolation of stein cells is based on the increased efflux of Hoechst 33342 lipophilic dye mediated by ABCG2, all ATP-binding cassette transporter which is highly expressed it) various stern cells. We found ABCG2 expression to be present at later stages of spermatogenesis. Western Nor analysis using all anti-ABCG2 antibody revealed expression of a 72 kDa band in mature sperm obtained from mice, rats, bulls or humans. Immunocytochemistry Studies revealed acrosomal staining pattern of ABCG2 in spermatozoa. Experiments Using the Hoechst 33342 ABCG2 substrate and the ABCG2-specific inhibitor FTC demonstrated efflux activity of ABCG2 in mature sperm. Incubation of sperm in capacitating medium in the presence of the ABCG2-inhibitor FTC resulted in decreased cholesterol depletion compared to sperm incubated in the absence of FTC. Our results demonstrate that ABCG2 is expressed at the acrosome in mature sperm. ABCG2 may thus serve to mediate cholesterol removal. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Scharenberg, Christian; Mannowetz, Nadja; Repges, Philip; Sahrhage, Tim; Jaehn, Thomas; Wennemuth, Gunther] Univ Saarland, Dept Anat & Cell Biol, D-66421 Homburg, Germany.
[Scharenberg, Christian; Brendel, Cornelia] Univ Marburg, Dept Hematol & Oncol, D-35037 Marburg, Germany.
[Robey, Robert W.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wennemuth, G (reprint author), Univ Saarland, Dept Anat & Cell Biol, Bldg 61, D-66421 Homburg, Germany.
EM gunther.wennemuth@uks.eu
NR 24
TC 7
Z9 8
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 9
PY 2009
VL 378
IS 2
BP 302
EP 307
DI 10.1016/j.jbbrc.2008.11.058
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 389AU
UT WOS:000262063100031
PM 19032939
ER
PT J
AU Pessoa, L
Rossi, A
Japee, S
Desimone, R
Ungerleider, LG
AF Pessoa, Luiz
Rossi, Andrew
Japee, Shruti
Desimone, Robert
Ungerleider, Leslie G.
TI Attentional control during the transient updating of cue information
SO BRAIN RESEARCH
LA English
DT Article
DE Attention; Vision; fMRI
ID EVENT-RELATED FMRI; TOP-DOWN CONTROL; SELECTIVE VISUAL-ATTENTION;
PREFRONTAL CORTEX; NEURAL MECHANISMS; COGNITIVE CONTROL; ANTERIOR
CINGULATE; BRAIN; PARIETAL; AREAS
AB The goal of the present study was to investigate the neural correlates of top-down control of switching behavior in humans and to contrast them to those observed during switching behavior guided by bottom-up mechanisms. In the main experimental condition (color-cue), which was guided by top-down control, a central cue indicated the color of a peripheral grating on which the subject performed an orientation judgment. For switch trials, the color of the cue on the current trial was different from the color on the previous trial, For non-switch trials, the color of the cue on the cur-rent trial was the same as the color in the preceding trial. During a control condition (pop-out), which was guided by bottom-up saliency, the target grating was defined by color contrast; again both switch and non-switch trials occurred. We observed stronger evoked responses during the color-cue task relative to the pop-out task in the inferior parietal lobule (IPL), frontal eye field (FEF), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). The contrast of switch vs. non-switch trials revealed activations in regions that were engaged when there was a change in the identity of the target. Collectively, switch trials evoked stronger responses relative to non-switch trials in fronto-parietal regions that appeared to be left lateralized, including left intraparietal sulcus (IPS) and left MFG/IFG. Task by trial type interactions (switch>non-switch during color-cue relative to pop-out) were observed in several fronto-parietal regions, including IPS, FEF, MFG and IFG, in addition to regions in visual cortex. Our findings suggest that, within the fronto-parietal attentional network, the IPS and MFG/IFG appear to be most heavily involved in attentive cue updating. Furthermore, several visual regions engaged by oriented gratings were strongly affected by cue updating, raising the possibility that they were the recipient of top-down signals that were generated when cue information was updated. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Pessoa, Luiz] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Rossi, Andrew] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
[Japee, Shruti; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Desimone, Robert] MIT, McGovern Inst, Cambridge, MA 02139 USA.
RP Pessoa, L (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA.
EM lpessoa@indiana.edu
FU NIMH Intramural Research Program; [R01MH071589]; [5R01EY017292]
FX We thank David Sturman and Aurora Ramos for assistance in this project
and Ziad Saad for help with surface mapping. This work was supported by
the NIMH Intramural Research Program. L.P. was supported in part by
R01MH071589 and R. D. was supported in part by 5R01EY017292.
NR 51
TC 17
Z9 17
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JAN 9
PY 2009
VL 1247
BP 149
EP 158
DI 10.1016/j.brainres.2008.10.010
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 401FR
UT WOS:000262925700016
PM 18992228
ER
PT J
AU Cui, KR
Zang, CZ
Roh, TY
Schones, DE
Childs, RW
Peng, WQ
Zhao, K
AF Cui, Kairong
Zang, Chongzhi
Roh, Tae-Young
Schones, Dustin E.
Childs, Richard W.
Peng, Weiqun
Zhao, Keji
TI Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells
Indicate the Fate of Bivalent Genes during Differentiation
SO Cell Stem Cell
LA English
DT Article
ID BETA-GLOBIN GENE; HUMAN GENOME; DNA METHYLATION; HISTONE MODIFICATIONS;
ERYTHROID-CELLS; TRANSCRIPTION; LINEAGE; PLURIPOTENT; PROGENITORS;
EXPRESSION
AB Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem cells/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1, and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these monomethylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1, and RNA polymerase 11 in HSCs/HPCs. Thus, our data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
C1 [Cui, Kairong; Roh, Tae-Young; Schones, Dustin E.; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Zang, Chongzhi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
RI Zang, Chongzhi/D-1445-2011
FU National Institutes of Health, National Heart, Lung, and Blood Institute
FX We thank Dr. Susan Wong for helpful discussions and Dr. Warren Leonard
for critical reading of the manuscript. The gene expression analysis
using the Affymetrix microarrays was performed by the Gene Expression
Core Facility of the National Heart, Lung, and Blood Institute. This
work was supported by the Intramural Research Program of the National
Institutes of Health, National Heart, Lung, and Blood Institute.
NR 46
TC 349
Z9 355
U1 3
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JAN 9
PY 2009
VL 4
IS 1
BP 80
EP 93
DI 10.1016/j.stem.2008.11.011
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 395YN
UT WOS:000262559500014
PM 19128795
ER
PT J
AU Jarczowski, F
Jahreis, G
Erdmann, F
Schierhorn, A
Fischer, G
Edlich, F
AF Jarczowski, Franziska
Jahreis, Guenther
Erdmann, Frank
Schierhorn, Angelika
Fischer, Gunter
Edlich, Frank
TI FKBP36 Is an Inherent Multifunctional Glyceraldehyde-3-phosphate
Dehydrogenase Inhibitor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PACHYTENE PRIMARY SPERMATOCYTES; GENE-EXPRESSION; RAT TESTES; HSP90;
TISSUES; PROTEIN; CELLS; GAPDH; RNA
AB FKBP36 has been previously shown to be a crucial factor in spermatogenesis because of its interplay with the synaptonemal complex protein SCPI. Here we show that beyond this function, FKBP36 forms complexes with glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) and Hsp90. Both proteins bind independently to different sites of the FKBP36 tetratricopeptide repeat domain. The interaction between FKBP36 and GAPDH directly inhibits the catalytic activity of GAPDH. In addition, FKBP36 expression causes a significant reduction of the GAPDH level and activity in COS-7 cells. Particularly in the cytosolic fraction, GAPDH was depleted by FKBP36 expression. Thus, FKBP36 diminishes GAPDH activity by direct interaction and down-regulation of GAPDH, which represents a previously unknown mechanism of GAPDH regulation and a novel function of FKBP36 in testis-specific signaling.
C1 [Jarczowski, Franziska; Jahreis, Guenther; Erdmann, Frank; Schierhorn, Angelika; Fischer, Gunter; Edlich, Frank] Max Planck Res Unit Enzymol Prot Folding, D-06120 Halle, Germany.
RP Edlich, F (reprint author), NINDS, Surg Neurol Branch, NIH, Porter Neurosci Res Ctr, 35 Convent Dr,MSC 3704, Bethesda, MD 20892 USA.
EM fischer@enzyme-halle.mpg.de; edlichf@ninds.nih.gov
FU Sonderforschungsbereich 604 of the Deutsche Forschungsgemeinschaft
FX This work was supported by Sonderforschungsbereich 604 of the Deutsche
Forschungsgemeinschaft. The costs of publication of this article were
defrayed in part by the payment of page charges. This article must
therefore be hereby marked "advertisement" in accordance with 18 U. S.
C. Section 1734 solely to indicate this fact.
NR 33
TC 10
Z9 12
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 JAN 9
PY 2009
VL 284
IS 2
BP 766
EP 773
DI 10.1074/jbc.M709779200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 389VP
UT WOS:000262122900010
PM 19001379
ER
PT J
AU Isenberg, JS
Annis, DS
Pendrak, ML
Ptaszynska, M
Frazier, WA
Mosher, DF
Roberts, DD
AF Isenberg, Jeff S.
Annis, Douglas S.
Pendrak, Michael L.
Ptaszynska, Malgorzata
Frazier, William A.
Mosher, Deane F.
Roberts, David D.
TI Differential Interactions of Thrombospondin-1,-2, and-4 with CD47 and
Effects on cGMP Signaling and Ischemic Injury Responses
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INTEGRIN-ASSOCIATED PROTEIN; C-TERMINAL DOMAIN; GROWTH-FACTOR-I;
NITRIC-OXIDE; TISSUE SURVIVAL; CELL RESPONSES; MYOCARDIAL-INFARCTION;
SIGNATURE DOMAINS; LIGAND-BINDING; RECEPTOR
AB Thrombospondin-1 regulates nitric oxide (NO) signaling in vascular cells via CD47. Because CD47 binding motifs are conserved in the C-terminal signature domains of all five thrombospondins and indirect evidence has implied CD47 interactions with other family members, we compared activities of recombinant signature domains of thrombospondin-1, -2, and -4 to interact with CD47 and modulate cGMP signaling. Signature domains of thrombospondin-2 and -4 were less active than that of thrombospondin-1 for inhibiting binding of radiolabeled signature domain of thrombospondin-1 or SIRP alpha (signal-regulatory protein) to cells expressing CD47. Consistent with this binding selectivity, the signature domain of thrombospondin-1 was more potent than those of thrombospondin-2 or -4 for inhibiting NO-stimulated cGMP synthesis in vascular smooth muscle cells and downstream effects on cell adhesion. In contrast to thrombospondin-1-and CD47-null cells, primary vascular cells from thrombospondin-2-null mice lack enhanced basal and NO-stimulated cGMP signaling. Effects of endogenous thrombospondin-2 on NO/cGMP signaling could be detected only in thrombospondin-1-null cells. Furthermore, tissue survival of ischemic injury and acute recovery of blood flow in thrombospondin-2-nulls resembles that of wild type mice. Therefore, thrombospondin-1 is the dominant regulator of NO/cGMP signaling via CD47, and its limiting role in acute ischemic injury responses is not shared by thrombospondin-2.
C1 [Isenberg, Jeff S.; Pendrak, Michael L.; Ptaszynska, Malgorzata; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Annis, Douglas S.; Mosher, Deane F.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA.
[Annis, Douglas S.; Mosher, Deane F.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
[Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU National Institutes of Health [HL54462, HL54390]; Intramural Research
Program of the NCI; Center for Cancer Research
FX This work was supported, in whole or in part, by National Institutes of
Health Grants National HL54462 (to D. F. M.) and HL54390 (to W. A. F.)
and by the Intramural Research Program of the NCI, National Institutes
of Health, Center for Cancer Research (to D. D. R.). The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 48
TC 57
Z9 58
U1 3
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 JAN 9
PY 2009
VL 284
IS 2
BP 1116
EP 1125
DI 10.1074/jbc.M804860200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 389VP
UT WOS:000262122900048
PM 19004835
ER
PT J
AU Pu, YM
Garfield, SH
Kedei, N
Blumberg, PM
AF Pu, Yongmei
Garfield, Susan H.
Kedei, Noemi
Blumberg, Peter M.
TI Characterization of the Differential Roles of the Twin C1a and C1b
Domains of Protein Kinase C delta
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHORBOL ESTER BINDING; 12-MYRISTATE 13-ACETATE; INDUCED TRANSLOCATION;
THERAPEUTIC TARGET; DOWN-REGULATION; NIH 3T3-CELLS; DIACYLGLYCEROL;
ACTIVATION; LIGANDS; PKC
AB Classic and novel protein kinase C (PKC) isozymes contain two zinc finger motifs, designated "C1a" and "C1b" domains, which constitute the recognition modules for the second messenger diacylglycerol (DAG) or the phorbol esters. However, the individual contributions of these tandem C1 domains to PKC function and, reciprocally, the influence of protein context on their function remain uncertain. In the present study, we prepared PKC delta constructs in which the individual C1a and C1b domains were deleted, swapped, or substituted for one another to explore these issues. As isolated fragments, both the delta C1a and delta C1b domains potently bound phorbol esters, but the binding of [(3)H] phorbol 12,13-dibutyrate ([(3)H]PDBu) by the delta C1a domain depended much more on the presence of phosphatidylserine than did that of the delta C1b domain. In intact PKC delta, the delta C1b domain played the dominant role in [(3)H]PDBu binding, membrane translocation, and down-regulation. A contribution from the delta C1a domain was nonetheless evident, as shown by retention of [(3)H]PDBu binding at reduced affinity, by increased [(3)H]PDBu affinity upon expression of a second delta C1a domain substituting for the delta C1b domain, and by loss of persistent plasma membrane translocation for PKC delta expressing only the delta C1b domain, but its contribution was less than predicted from the activity of the isolated domain. Switching the position of the delta C1b domain to the normal position of the delta C1a domain (or vice versa) had no apparent effect on the response to phorbol esters, suggesting that the specific position of the C1 domain within PKC delta was not the primary determinant of its activity.
C1 [Garfield, Susan H.; Blumberg, Peter M.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pu, Yongmei; Kedei, Noemi; Blumberg, Peter M.] Lab Canc Biol & Genet, Mol Mech Tumor Promot Sect, Bethesda, MD 20892 USA.
RP Blumberg, PM (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4048,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
EM blumberp@dc37a.nci.nih.gov
FU National Institutes of Health; NCI; Center for Cancer Research
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program, NCI, Center for Cancer Research.
NR 46
TC 11
Z9 11
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 9
PY 2009
VL 284
IS 2
BP 1302
EP 1312
DI 10.1074/jbc.M804796200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 389VP
UT WOS:000262122900065
PM 19001377
ER
PT J
AU Kann, MG
Shoemaker, BA
Panchenko, AR
Przytycka, TM
AF Kann, Maricel G.
Shoemaker, Benjamin A.
Panchenko, Anna R.
Przytycka, Teresa M.
TI Correlated Evolution of Interacting Proteins: Looking Behind the
Mirrortree
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE domain-domain interactions; protein coevolution; protein-protein
interactions; phylogenetic tree; mirrortree
ID DOMAIN INTERACTIONS; DISTANCE MATRICES; REVEALS INSIGHTS; COEVOLUTION;
INFORMATION; SPECIFICITY; PREDICTION; NETWORKS; TREE
AB It has been observed that the evolutionary distances of interacting proteins often display a higher level of similarity than those of noninteracting proteins. This finding indicates that interacting proteins are subject to common evolutionary constraints and constitutes the basis of a method to predict protein interactions known as mirrortree. It has been difficult, however, to identify the direct cause of the observed similarities between evolutionary trees. One possible explanation is the existence of compensatory mutations between partners' binding sites to maintain proper binding. This explanation, though, has been recently challenged, and it has been suggested that the signal of correlated evolution uncovered by the mirrortree method is unrelated to any correlated evolution between binding sites. We examine the contribution of binding sites to the correlation between evolutionary trees of interacting domains. We show that binding neighborhoods of interacting proteins have, on average, higher coevolutionary signal compared with the regions outside binding sites; however, when the binding neighborhood is removed, the remaining domain sequence still contains some coevolutionary signal. In conclusion, the correlation between evolutionary trees of interacting domains cannot exclusively be attributed to the correlated evolution of the binding sites or to common evolutionary pressure exerted on the whole protein domain sequence, each of which contributes to the signal measured by the mirrortree approach. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Kann, Maricel G.] Univ Maryland, Dept Biol Sci, Baltimore Cty, MD 21250 USA.
[Shoemaker, Benjamin A.; Panchenko, Anna R.; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Kann, MG (reprint author), Univ Maryland, Dept Biol Sci, Baltimore Cty, MD 21250 USA.
EM mkann@umbc.edu; przytyck@ncbi.nlm.nih.gov
RI Kann, Maricel/E-5701-2012
FU Intramural Research Program of the National Institutes of Health;
National Library of Medicine; University of Maryland Baltimore County
Special Research Initiative Support
FX Support for this work was provided in part by the Intramural Research
Program of the National Institutes of Health, National Library of
Medicine, and through funding from the University of Maryland Baltimore
County Special Research Initiative Support.
NR 31
TC 33
Z9 34
U1 1
U2 9
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 JAN 9
PY 2009
VL 385
IS 1
BP 91
EP 98
DI 10.1016/j.jmb.2008.09.078
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 400LT
UT WOS:000262870200011
PM 18930732
ER
PT J
AU Abbadessa, G
Accolla, R
Aiuti, F
Albini, A
Aldovini, A
Alfano, M
Antonelli, G
Bartholomew, C
Bentwich, Z
Bertazzoni, U
Berzofsky, JA
Biberfeld, P
Boeri, E
Buonaguro, L
Buonaguro, FM
Bukrinsky, M
Burny, A
Caruso, A
Cassol, S
Chandra, P
Ceccherini-Nelli, L
Chieco-Bianchi, L
Clerici, M
Colombini-Hatch, S
Morghen, CDG
De Maria, A
De Rossi, A
Dierich, M
Della-Favera, R
Dolei, A
Douek, D
Erfle, V
Felber, B
Fiorentini, S
Franchini, G
Gershoni, JM
Gotch, F
Green, P
Greene, WC
Hall, W
Haseltine, W
Jacobson, S
Kallings, LO
Kalyanaraman, VS
Katinger, H
Khalili, K
Klein, G
Klein, E
Klotman, M
Klotman, P
Kotler, M
Kurth, R
Lafeuillade, A
La Placa, M
Lewis, J
Lillo, F
Lisziewicz, J
Lomonico, A
Lopalco, L
Lori, F
Lusso, P
Macchi, B
Malim, M
Margolis, L
Markham, PD
Mcclure, M
Miller, N
Mingari, MC
Moretta, L
Noonan, D
O'Brien, S
Okamoto, T
Pal, R
Palese, P
Panet, A
Pantaleo, G
Pavlakis, G
Pistello, M
Plotkin, S
Poli, G
Pomerantz, R
Radaelli, A
Robert-Guroff, M
Roederer, M
Sarngadharan, MG
Schols, D
Secchiero, P
Shearer, G
Siccardi, A
Stevenson, M
Svoboda, J
Tartaglia, J
Torelli, G
Tornesello, ML
Tschachler, E
Vaccarezza, M
Vallbracht, A
Van Lunzen, J
Varnier, O
Vicenzi, E
Von Melchner, H
Witz, I
Zagury, D
Zagury, JF
Zauli, G
Zipeto, D
AF Abbadessa, Giovanni
Accolla, Roberto
Aiuti, Fernando
Albini, Adriana
Aldovini, Anna
Alfano, Massimo
Antonelli, Guido
Bartholomew, Courtenay
Bentwich, Zvi
Bertazzoni, Umberto
Berzofsky, Jay A.
Biberfeld, Peter
Boeri, Enzo
Buonaguro, Luigi
Buonaguro, Franco M.
Bukrinsky, Michael
Burny, Arsene
Caruso, Arnaldo
Cassol, Sharon
Chandra, Prakash
Ceccherini-Nelli, Luca
Chieco-Bianchi, Luigi
Clerici, Mario
Colombini-Hatch, Sandra
Morghen, Carlo De Giuli
De Maria, Andrea
De Rossi, Anita
Dierich, Manfred
Della-Favera, Riccardo
Dolei, Antonina
Douek, Daniel
Erfle, Volker
Felber, Barbara
Fiorentini, Simona
Franchini, Genoveffa
Gershoni, Jonathan M.
Gotch, Frances
Green, Patrick
Greene, Warner C.
Hall, William
Haseltine, William
Jacobson, Stephens
Kallings, Lars O.
Kalyanaraman, Vaniambadi S.
Katinger, Hermann
Khalili, Kamel
Klein, George
Klein, Eva
Klotman, Mary
Klotman, Paul
Kotler, Moshe
Kurth, Reinhard
Lafeuillade, Alain
La Placa, Michelangelo
Lewis, Jonathan
Lillo, Flavia
Lisziewicz, Julianna
Lomonico, Anita
Lopalco, Lucia
Lori, Franco
Lusso, Paolo
Macchi, Beatrice
Malim, Michael
Margolis, Leonid
Markham, Phillip D.
Mcclure, Myra
Miller, Nancy
Mingari, Maria C.
Moretta, Lorenzo
Noonan, Douglas
O'Brien, Steve
Okamoto, Takashi
Pal, Ranajit
Palese, Peter
Panet, Amos
Pantaleo, Giuseppe
Pavlakis, George
Pistello, Mauro
Plotkin, Stanley
Poli, Guido
Pomerantz, Roger
Radaelli, Antonia
Robert-Guroff, Marjorie
Roederer, Mario
Sarngadharan, Mangalasseril G.
Schols, Dominique
Secchiero, Paola
Shearer, Gene
Siccardi, Antonio
Stevenson, Mario
Svoboda, Jan
Tartaglia, Jim
Torelli, Giuseppe
Tornesello, Maria Lina
Tschachler, Erwin
Vaccarezza, Mauro
Vallbracht, Angelika
Van Lunzen, Jan
Varnier, Oliviero
Vicenzi, Elisa
Von Melchner, Harald
Witz, Isaac
Zagury, Daniel
Zagury, Jean-Francois
Zauli, Giorgio
Zipeto, Donato
TI Unsung Hero Robert C. Gallo
SO SCIENCE
LA English
DT Letter
ID RETROVIRUSES HTLV-III; AIDS
C1 [Alfano, Massimo; Boeri, Enzo; Lopalco, Lucia; Poli, Guido; Vicenzi, Elisa] San Raffaele Univ & Sci Inst, Milan, Italy.
[Abbadessa, Giovanni; Lewis, Jonathan] ZIOPHARM Oncol Inc, Boston, MA USA.
[Accolla, Roberto; Noonan, Douglas] Univ Insubria, Varese, Italy.
[Aiuti, Fernando; Antonelli, Guido] Univ Roma La Sapienza, Rome, Italy.
[Albini, Adriana] IRCCS Multimedica, Milan, Italy.
[Aldovini, Anna] Childrens Hosp, Boston, MA 02115 USA.
[Aldovini, Anna] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bartholomew, Courtenay] Med Res Fdn Trinidad & Tobago, Port Of Spain, Trinid & Tobago.
[Bentwich, Zvi] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel.
[Bertazzoni, Umberto; Zipeto, Donato] Univ Verona, I-37100 Verona, Italy.
[Berzofsky, Jay A.; Franchini, Genoveffa; Lomonico, Anita; Robert-Guroff, Marjorie; Shearer, Gene] NCI, Bethesda, MD 20892 USA.
[Biberfeld, Peter; Klein, George; Klein, Eva] Karolinska Inst, Stockholm, Sweden.
[Buonaguro, Luigi; Buonaguro, Franco M.; Tornesello, Maria Lina] Ist Nazl Tumori Fdn G Pascale, Naples, Italy.
[Bukrinsky, Michael] George Washington Univ, Washington, DC USA.
[Burny, Arsene] Ctr Cellular & Mol Biol, Gembloux, Belgium.
[Caruso, Arnaldo; Fiorentini, Simona] Univ Brescia, Brescia, Italy.
[Cassol, Sharon] Univ Pretoria, ZA-0002 Pretoria, South Africa.
[Chandra, Prakash; Von Melchner, Harald] Univ Frankfurt, Sch Med, Frankfurt, Germany.
[Ceccherini-Nelli, Luca; Pistello, Mauro] Univ Pisa, Pisa, Italy.
[Chieco-Bianchi, Luigi; De Rossi, Anita] Univ Padua, Padua, Italy.
[Clerici, Mario; Morghen, Carlo De Giuli; Radaelli, Antonia; Siccardi, Antonio] Univ Milan, Milan, Italy.
[Colombini-Hatch, Sandra] NHLBI, Bethesda, MD 20892 USA.
[De Maria, Andrea; Mingari, Maria C.; Varnier, Oliviero] Univ Genoa, Genoa, Italy.
[Dierich, Manfred] Innsbruck Med Univ, Innsbruck, Austria.
[Della-Favera, Riccardo] Columbia Univ, New York, NY USA.
[Dolei, Antonina] Univ Sassari, I-07100 Sassari, Italy.
[Douek, Daniel; Lusso, Paolo; Miller, Nancy; Roederer, Mario] NIAID, Bethesda, MD 20892 USA.
[Erfle, Volker] GSF, Inst Mol Virol, Munich, Germany.
[Felber, Barbara; O'Brien, Steve; Pavlakis, George] NCI, Frederick, MD 21701 USA.
[Gershoni, Jonathan M.; Witz, Isaac] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Gotch, Frances; Mcclure, Myra] Univ London Imperial Coll Sci Technol & Med, London, England.
[Green, Patrick] Ohio State Univ, Columbus, OH 43210 USA.
[Greene, Warner C.] Gladstone Inst Virol & Immunol, San Francisco, CA USA.
[Hall, William] Univ Coll Dublin, Dublin 2, Ireland.
[Haseltine, William] William A Haseltine Fdn Med Sci & Arts, Rockville, MD USA.
[Jacobson, Stephens] NINDS, Bethesda, MD 20892 USA.
[Kallings, Lars O.] UN, Secretariat Gen, New York, NY 10017 USA.
[Kalyanaraman, Vaniambadi S.; Markham, Phillip D.; Pal, Ranajit; Sarngadharan, Mangalasseril G.] Adv Biosci Labs, Kensington, MD USA.
[Katinger, Hermann] Univ Nat Resources & Appl Life, Vienna, Austria.
[Khalili, Kamel] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Klotman, Mary; Klotman, Paul; Palese, Peter] Mt Sinai Sch Med, New York, NY USA.
[Kotler, Moshe; Panet, Amos] Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel.
[Kurth, Reinhard] Robert Koch Inst, D-1000 Berlin, Germany.
[Lafeuillade, Alain] Hosp Font Pre, Toulon, France.
[La Placa, Michelangelo] Univ Bologna, Bologna, Italy.
[Lillo, Flavia] Fdn San Raffaele G Giglio, Cefalu, Italy.
[Lisziewicz, Julianna; Lori, Franco] Genet Immun, Budapest, Hungary.
[Macchi, Beatrice] Univ Roma Tor Vergata, I-00173 Rome, Italy.
[Malim, Michael] Kings Coll London, Sch Med, London WC2R 2LS, England.
[Margolis, Leonid] NICHHD, Bethesda, MD 20892 USA.
[Moretta, Lorenzo] Ist Giannina Gaslini, I-16148 Genoa, Italy.
[Okamoto, Takashi] Nagoya City Univ, Nagoya, Aichi, Japan.
[Pantaleo, Giuseppe] CHU Vaudois, CH-1011 Lausanne, Switzerland.
[Plotkin, Stanley] Sanofi Pasteur, Doylestown, PA USA.
[Pomerantz, Roger] Tibotec Pharmaceut Ltd, Yardley, PA USA.
[Schols, Dominique] Katholieke Univ Leuven, Rega Inst, Louvain, Belgium.
[Secchiero, Paola; Zauli, Giorgio] Univ Ferrara, I-44100 Ferrara, Italy.
[Stevenson, Mario] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Svoboda, Jan] Inst Mol Genet, Prague, Czech Republic.
[Tartaglia, Jim] Sanofi Pasteur, Toronto, ON, Canada.
[Torelli, Giuseppe] Univ Modena, I-41100 Modena, Italy.
[Tschachler, Erwin] Med Univ Vienna, Vienna, Austria.
[Vaccarezza, Mauro] Univ Cassino, I-03043 Cassino, Italy.
[Vallbracht, Angelika] Univ Bremen, Bremen, Germany.
[Van Lunzen, Jan] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Zagury, Daniel] Neovscs SA, Paris, France.
[Zagury, Jean-Francois] Conservatoire Natl Arts & Metiers, Paris, France.
RP Poli, G (reprint author), San Raffaele Univ & Sci Inst, Milan, Italy.
EM poli.guido@hsr.it
RI Svoboda, Jan/G-4393-2014; Tornesello, Maria Lina/A-1564-2009; secchiero,
paola/G-9689-2015; De Rossi, Anita/L-3128-2015; klotman,
mary/A-1921-2016; de maria, andrea/F-7116-2016; Pantaleo,
Giuseppe/K-6163-2016; Noonan, Douglas/A-8620-2010;
OI Lopalco, Lucia/0000-0003-3812-1759; Tornesello, Maria
Lina/0000-0002-3523-3264; secchiero, paola/0000-0003-4101-7987; De
Rossi, Anita/0000-0001-6435-7509; de maria, andrea/0000-0001-5782-333X;
Noonan, Douglas/0000-0001-8058-0719; Radaelli,
Antonia/0000-0002-5683-6216; Palese, Peter/0000-0002-0337-5823; Vicenzi,
Elisa/0000-0003-0051-3968; Malim, Michael/0000-0002-7699-2064; Accolla,
Roberto/0000-0003-2493-7378; Zauli, Giorgio/0000-0002-3750-8698;
VACCAREZZA, Mauro/0000-0003-3060-318X
NR 5
TC 2
Z9 2
U1 2
U2 16
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 JAN 9
PY 2009
VL 323
IS 5911
BP 206
EP 207
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 392GG
UT WOS:000262290600012
PM 19131607
ER
PT J
AU Turanov, AA
Lobanov, AV
Fomenko, DE
Morrison, HG
Sogin, ML
Klobutcher, LA
Hatfield, DL
Gladyshev, VN
AF Turanov, Anton A.
Lobanov, Alexey V.
Fomenko, Dmitri E.
Morrison, Hilary G.
Sogin, Mitchell L.
Klobutcher, Lawrence A.
Hatfield, Dolph L.
Gladyshev, Vadim N.
TI Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon
SO SCIENCE
LA English
DT Article
ID SEQUENCE ELEMENT; TRANSFER-RNA; EXPRESSION
AB Strict one- to- one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3 ' untranslated region structure and location of the dual- function codon within the messenger RNA ( mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location- dependent dual function of UGA when expressed in mammalian cells. Thus, the genetic code supports the use of one codon to code for multiple amino acids.
C1 [Turanov, Anton A.; Lobanov, Alexey V.; Fomenko, Dmitri E.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
[Turanov, Anton A.; Lobanov, Alexey V.; Fomenko, Dmitri E.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA.
[Morrison, Hilary G.; Sogin, Mitchell L.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA.
[Klobutcher, Lawrence A.] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT 06032 USA.
[Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
EM vgladyshev1@unl.edu
RI Gladyshev, Vadim/A-9894-2013;
OI Morrison, Hilary/0000-0003-0281-326X
FU NIH [GM061603, GM065204, AI058054]; NSF [0343813]; Intramural Research
Program; National Cancer Institute
FX We thank K. Hammar for constructing the EST library and I. Sorokina
(Midwest Bio Services) for protein sequencing. This work was supported
by NIH GM061603 and GM065204 to V.N.G., AI058054 to M.L.S., NSF 0343813
to L.A.K., and the Intramural Research Program, National Cancer
Institute, NIH, to D.L.H. Sequences for tRNA and selenoprotein genes
have been deposited in the GenBank database under accession numbers
FJ440148 to FJ440159.
NR 10
TC 54
Z9 56
U1 1
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 9
PY 2009
VL 323
IS 5911
BP 259
EP 261
DI 10.1126/science.1164748
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 392GG
UT WOS:000262290600040
PM 19131629
ER
PT J
AU Wei, J
Rega, MF
Kitada, S
Yuan, HB
Zhai, D
Risbood, P
Seltzman, HH
Twine, CE
Reed, JC
Pellecchia, M
AF Wei, Jun
Rega, Michele F.
Kitada, Shinichi
Yuan, Hongbin
Zhai, Dayong
Risbood, Prabhakar
Seltzman, Herbert H.
Twine, Charles E.
Reed, John C.
Pellecchia, Maurizio
TI Synthesis and evaluation of Apogossypol atropisomers as potential
Bcl-x(L) antagonists
SO CANCER LETTERS
LA English
DT Article
DE Apogossypol atropisomers; Gossypol; Apoptosis; Bcl-2; Bcl-x(L);
Apogossypol; Chemotherapy; Mcl-1
ID SMALL-MOLECULE INHIBITORS; BCL-2 FAMILY PROTEINS; GOSSYPOL ENANTIOMERS;
APOPTOSIS; CANCER; DISCOVERY; COMPOUND; COMPLEX; DESIGN; CELLS
AB Anti-apoptotic Bcl-2 family proteins such as Bcl-2 and Bcl-X-L have been recently validated as targets for the discovery of novel anti-cancer agents. We previously reported that racemic (+/-) Apogossypol, a semi-synthetic compound derived from the natural product Gossypol, binds and inhibits Bcl-2 and Bcl-X-L. in vitro and in cell. Given that (+) and (-) Gossypol display different proapoptotic activities, here we report on the synthesis of (+) and (-) Apogossypol and the evaluation of their in vitro and cellular activity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Wei, Jun; Rega, Michele F.; Kitada, Shinichi; Yuan, Hongbin; Zhai, Dayong; Reed, John C.; Pellecchia, Maurizio] Burnham Inst Med Res, La Jolla, CA 92037 USA.
[Risbood, Prabhakar] NCI, Drug Synth & Chem Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA.
[Seltzman, Herbert H.; Twine, Charles E.] RTI Int, Res Triangle Pk, NC 27709 USA.
RP Pellecchia, M (reprint author), Burnham Inst Med Res, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM mpellecchia@burnham.org
FU NIH [U01 A1061139]; Coronado Biosciences; [CSRA 08-02]
FX We thank NIH (Grant No. U01 A1061139) and Coronado Biosciences (CSRA
#08-02) for financial support and the NCI-RAID program for technical and
scientific support.
NR 26
TC 18
Z9 19
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD JAN 8
PY 2009
VL 273
IS 1
BP 107
EP 113
DI 10.1016/j.canlet.2008.07.031
PG 7
WC Oncology
SC Oncology
GA 396HS
UT WOS:000262583400012
PM 18782651
ER
PT J
AU Munday, JN
Capasso, F
Parsegian, VA
AF Munday, J. N.
Capasso, Federico
Parsegian, V. Adrian
TI Measured long-range repulsive Casimir-Lifshitz forces
SO NATURE
LA English
DT Article
ID DER-WAALS FORCES; MU-M; ATTRACTION; PHYSICS; SOLIDS; SILICA
AB Quantum fluctuations create intermolecular forces that pervade macroscopic bodies(1-3). At molecular separations of a few nanometres or less, these interactions are the familiar van der Waals forces(4). However, as recognized in the theories of Casimir, Polder and Lifshitz(5-7), at larger distances and between macroscopic condensed media they reveal retardation effects associated with the finite speed of light. Although these long- range forces exist within all matter, only attractive interactions have so far been measured between material bodies(8-11). Here we show experimentally that, in accord with theoretical prediction(12), the sign of the force can be changed from attractive to repulsive by suitable choice of interacting materials immersed in a fluid. The measured repulsive interaction is found to be weaker than the attractive. However, in both cases the magnitude of the force increases with decreasing surface separation. Repulsive Casimir - Lifshitz forces could allow quantum levitation of objects in a fluid and lead to a new class of switchable nanoscale devices with ultra-low static friction(13-15).
C1 [Capasso, Federico] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Munday, J. N.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[Parsegian, V. Adrian] NIH, Bethesda, MD 20892 USA.
RP Capasso, F (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM capasso@seas.harvard.edu
RI Munday, Jeremy/E-6512-2016
OI Munday, Jeremy/0000-0002-0881-9876
FU Center for Nanoscale Systems at Harvard University; Intramural Research
Program of the NIH; Eunice Kennedy Shriver National Institute of Child
Health and Human Development; NSF
FX We thank D. Iannuzzi, R. Podgornik, J. Zimmerberg, S. M. Bezrukov and M.
B. Romanowsky for discussions. This project was partially supported by
the Center for Nanoscale Systems at Harvard University, and by the
Intramural Research Program of the NIH, Eunice Kennedy Shriver National
Institute of Child Health and Human Development. J.N.M. acknowledges
support from the NSF.
NR 30
TC 282
Z9 292
U1 3
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JAN 8
PY 2009
VL 457
IS 7226
BP 170
EP 173
DI 10.1038/nature07610
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 393GS
UT WOS:000262360200027
PM 19129843
ER
PT J
AU Tita, ATN
Landon, MB
Spong, CY
Lai, YL
Leveno, KJ
Varner, MW
Moawad, AH
Caritis, SN
Meis, PJ
Wapner, RJ
Sorokin, Y
Miodovnik, M
Carpenter, M
Peaceman, AM
O'Sullivan, MJ
Sibai, BM
Langer, O
Thorp, JM
Ramin, SM
Mercer, BM
AF Tita, Alan T. N.
Landon, Mark B.
Spong, Catherine Y.
Lai, Yinglei
Leveno, Kenneth J.
Varner, Michael W.
Moawad, Atef H.
Caritis, Steve N.
Meis, Paul J.
Wapner, Ronald J.
Sorokin, Yoram
Miodovnik, Menachem
Carpenter, Marshall
Peaceman, Alan M.
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
Thorp, John M.
Ramin, Susan M.
Mercer, Brian M.
CA Eunice Kennedy Shriver NICHD
TI Timing of Elective Repeat Cesarean Delivery at Term and Neonatal
Outcomes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RESPIRATORY MORBIDITY; SECTION; LABOR; RISK; MODE; PREGNANCIES;
STILLBIRTH; INFANTS; TRIAL
AB Background Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term ( 37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes.
Methods We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal - Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively ( i. e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, newborn sepsis, and admission to the neonatal intensive care unit ( ICU).
Results Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation ( 6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome ( adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [ CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend < 0.001). The rates of adverse respiratory outcomes, mechanical ventilation, newborn sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks.
Conclusions Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.
C1 [Tita, Alan T. N.] Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35249 USA.
[Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Moawad, Atef H.] Univ Chicago, Chicago, IL 60637 USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Meis, Paul J.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
[Miodovnik, Menachem] Columbia Univ, New York, NY USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Sibai, Baha M.] Univ Tennessee, Memphis, TN USA.
[Langer, Oded] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Ramin, Susan M.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Tita, ATN (reprint author), Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, 619 19th St S, Birmingham, AL 35249 USA.
EM alan.tita@obgyn.uab.edu
RI Varner, Michael/K-9890-2013;
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973;
Peaceman, Alan/0000-0002-4515-4850
FU NICHD NIH HHS [U10 HD040560, HD001258, HD21410, HD21414, HD27860,
HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210,
HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, K12
HD001258, R24 HD050924, U01 HD036801, U10 HD021410, U10 HD027860, U10
HD027869, U10 HD027869-19, U10 HD027905, U10 HD027915, U10 HD027917, U10
HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10 HD036801, U10
HD040485, U10 HD040500, U10 HD040512, U10 HD040544, U10 HD040545, UG1
HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1
HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560]
NR 30
TC 347
Z9 369
U1 2
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 JAN 8
PY 2009
VL 360
IS 2
BP 111
EP U29
DI 10.1056/NEJMoa0803267
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 391UG
UT WOS:000262258300004
PM 19129525
ER
PT J
AU Rouse, DJ
Hirtz, DG
Thom, EA
AF Rouse, Dwight J.
Hirtz, Deborah G.
Thom, Elizabeth A.
CA Eunice Shriver Kennedy NICHHD
TI Magnesium Sulfate for the Prevention of Cerebral Palsy Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID TRIAL
C1 [Rouse, Dwight J.] Univ Alabama, Birmingham, AL 35249 USA.
[Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
[Thom, Elizabeth A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
RP Rouse, DJ (reprint author), Univ Alabama, Birmingham, AL 35249 USA.
EM drouse@uab.edu
NR 2
TC 3
Z9 3
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 8
PY 2009
VL 360
IS 2
BP 190
EP 190
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 391UG
UT WOS:000262258300025
ER
PT J
AU Alcaraz, A
Nestorovich, EM
Lopez, ML
Garcia-Gimenez, E
Bezrukov, SM
Aguilella, VM
AF Alcaraz, Antonio
Nestorovich, Ekaterina M.
Lidon Lopez, M.
Garcia-Gimenez, Elena
Bezrukov, Sergey M.
Aguilella, Vicente M.
TI Diffusion, Exclusion, and Specific Binding in a Large Channel: A Study
of OmpF Selectivity Inversion
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID LIQUID JUNCTION POTENTIALS; ELECTRICAL PROPERTIES; MEMBRANE-POTENTIALS;
PROTECTIVE ANTIGEN; CRYSTAL-STRUCTURES; IONIC SELECTIVITY;
ESCHERICHIA-COLI; CHARGE INVERSION; ANTHRAX TOXIN; PORIN
AB We find that moderate cationic selectivity of the general bacterial porin OmpF in sodium and potassium chloride solutions is inversed to anionic selectivity in concentrated solutions of barium, calcium, nickel, and magnesium chlorides. To understand the origin of this phenomenon, we consider several factors, which include the binding of divalent cations, electrostatic and steric exclusion of differently charged and differently sized ions, size-dependent hydrodynamic hindrance, electrokinetic effects, and significant "anionic" diffusion potential for bulk solutions of chlorides of divalent cations. Though all these factors contribute to the measured selectivity of this large channel, the observed selectivity inversion is mostly due to the following two. First, binding divalent cations compensates, or even slightly overcompensates, for the negative charge of the OmpF protein, which is known to be the main cause of cationic selectivity in sodium and potassium chloride solutions. Second, the higher anionic (versus cationic) transport rate expected for bulk solutions of chloride salts of divalent cations is the leading cause of the measured anionic selectivity of the channel. Interestingly, at high concentrations the binding of cations does not show any pronounced specificity within the divalent series because the reversal potentials measured in the series correlate well with the corresponding bulk diffusion potentials. Thus our study shows that, in contrast to the highly selective channels of neurophysiology that employ mostly the exclusion mechanism, quite different factors account for the selectivity of large channels. The elucidation of these factors is essential for understanding large channel selectivity and its regulation in vivo.
C1 [Alcaraz, Antonio; Lidon Lopez, M.; Garcia-Gimenez, Elena; Aguilella, Vicente M.] Univ Jaume 1, Dept Fis, Castellon de La Plana, Spain.
[Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Bethesda, MD 20892 USA.
RP Aguilella, VM (reprint author), Univ Jaume 1, Dept Fis, Castellon de La Plana, Spain.
EM aguilell@fca.uji.es
RI Aguilella, Vicente/B-7592-2008; Lopez Peris, Maria Lidon/P-5027-2014;
Alcaraz, Antonio/F-8498-2016
OI Aguilella, Vicente/0000-0002-2420-2649; Lopez Peris, Maria
Lidon/0000-0002-9599-8760;
FU Spanish Ministry of Education [FIS2007-60205]; National Institutes of
Health; Eunice Kennedy Shriver National Institute of Child Health and
Human Development
FX The authors are grateful to Adrian Parsegian for fruitful discussions
and reading parts of the manuscript.; We acknowledge support from the
Spanish Ministry of Education (project FIS2007-60205). This study was
also supported by the Intramural Research Program of the National
Institutes of Health, Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 53
TC 46
Z9 46
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JAN 7
PY 2009
VL 96
IS 1
BP 56
EP 66
DI 10.1016/j.bpj.2008.09.024
PG 11
WC Biophysics
SC Biophysics
GA 450BO
UT WOS:000266376200008
PM 19134471
ER
PT J
AU Sathyanarayana, BK
Hahn, Y
Patankar, MS
Pastan, I
Lee, B
AF Sathyanarayana, Bangalore K.
Hahn, Yoonsoo
Patankar, Manish S.
Pastan, Ira
Lee, Byungkook
TI Mesothelin, Stereocilin, and Otoancorin are predicted to have
superhelical structures with ARM-type repeats
SO BMC STRUCTURAL BIOLOGY
LA English
DT Article
ID INNER-EAR; SEQUENCE ALIGNMENT; MOLECULAR-CLONING; PROTEIN REPEATS;
COILED COILS; OVARIAN; RECOGNITION; ANNOTATION; EXPRESSION; PROFILES
AB Background: Mesothelin is a 40 kDa protein present on the surface of normal mesothelial cells and overexpressed in many human tumours, including mesothelioma and ovarian and pancreatic adenocarcinoma. It forms a strong and specific complex with MUC16, which is also highly expressed on the surface of mesothelioma and ovarian cancer cells. This binding has been suggested to be the basis of ovarian cancer metastasis. Knowledge of the structure of this protein will be useful, for example, in building a structural model of the MUC16-mesothelin complex. Mesothelin is produced as a precursor, which is cleaved by furin to produce the N-terminal half, which is called the megakaryocyte potentiating factor (MPF), and the C-terminal half, which is mesothelin. Little is known about the function of mesothelin and there is no information on its possible three-dimensional structure. Mesothelin has been reported to be homologous to the deafness-related inner ear proteins otoancorin and stereocilin, for neither of which the three-dimensional structure is known.
Results: The BLAST and PSI-BLAST searches confirmed that mesothelin and mesothelin precursor proteins are remotely homologous to stereocilin and otoancorin and more closely homologous to the hypothetical protein MPFL (MPF-like). Secondary structure prediction servers predicted a predominantly helical structure for both mesothelin and mesothelin precursor proteins and also for stereocilin and otoancorin. Three-dimensional structure prediction servers INHUB and I-TASSER produced structural models for mesothelin, which consisted of superhelical structures with ARM-type repeats in conformity with the secondary structure predictions. Similar ARM-type superhelical repeat structures were predicted by 3D-PSSM server for mesothelin precursor and for stereocilin and otoancorin proteins.
Conclusion: The mesothelin superfamily of proteins, which includes mesothelin, mesothelin precursor, megakaryocyte potentiating factor, MPFL, stereocilin and otoancorin, are predicted to have superhelical structures with ARM-type repeats. We suggest that all of these function as superhelical lectins to bind the carbohydrate moieties of extracellular glycoproteins.
C1 [Sathyanarayana, Bangalore K.; Hahn, Yoonsoo; Pastan, Ira; Lee, Byungkook] NIH, Natl Canc Inst, Ctr Canc Res, Lab Mol Biol, Bethesda, MD 20892 USA.
[Hahn, Yoonsoo] Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul 156756, South Korea.
[Patankar, Manish S.] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI USA.
RP Lee, B (reprint author), NIH, Natl Canc Inst, Ctr Canc Res, Lab Mol Biol, Bethesda, MD 20892 USA.
EM sathya@helix.nih.gov; yoonsoo.hahn@gmail.com; patankar@wisc.edu;
pastani@mail.nih.gov; bk@nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research
FX We thank Ms Chin-Hsien Tai for making the stereo drawing of Figure 3.
This research was supported in part by the Intramural Research Program
of the NIH, the National Cancer Institute, Center for Cancer Research.
NR 55
TC 14
Z9 14
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2237
J9 BMC STRUCT BIOL
JI BMC Struct. Biol.
PD JAN 7
PY 2009
VL 9
AR 1
DI 10.1186/1472-6807-9-1
PG 11
WC Biophysics
SC Biophysics
GA 407BE
UT WOS:000263337800001
PM 19128473
ER
PT J
AU Hall, KD
Heymsfield, SB
AF Hall, Kevin D.
Heymsfield, Steven B.
TI Models Use Leptin and Calculus to Count Calories
SO CELL METABOLISM
LA English
DT Editorial Material
ID BODY-WEIGHT; SET POINTS; FAT
AB Thermostats have "set-points" that engineers design with mathematical rigor. Work in this issue of Cell Metabolism (Tam et al., 2009) applies similar modeling strategies to explore the control of murine energy and body weight homeostasis by leptin.
C1 [Heymsfield, Steven B.] Merck Res Labs, Rahway, NJ 07065 USA.
[Hall, Kevin D.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Heymsfield, SB (reprint author), Merck Res Labs, POB 2000,RY34A-A238, Rahway, NJ 07065 USA.
EM steven_heymsfield@merck.com
RI Hall, Kevin/F-2383-2010
NR 12
TC 5
Z9 5
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD JAN 7
PY 2009
VL 9
IS 1
BP 3
EP 4
DI 10.1016/j.cmet.2008.12.006
PG 2
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 392WN
UT WOS:000262333000002
PM 19117539
ER
PT J
AU Lippman, SM
Klein, EA
Goodman, PJ
Lucia, MS
Thompson, IM
Ford, LG
Parnes, HL
Minasian, LM
Gaziano, JM
Hartline, JA
Parsons, JK
Bearden, JD
Crawford, ED
Goodman, GE
Claudio, J
Winquist, E
Cook, ED
Karp, DD
Walther, P
Lieber, MM
Kristal, AR
Darke, AK
Arnold, KB
Ganz, PA
Santella, RM
Albanes, D
Taylor, PR
Probstfield, JL
Jagpal, TJ
Crowley, JJ
Meyskens, FL
Baker, LH
Coltman, CA
AF Lippman, Scott M.
Klein, Eric A.
Goodman, Phyllis J.
Lucia, M. Scott
Thompson, Ian M.
Ford, Leslie G.
Parnes, Howard L.
Minasian, Lori M.
Gaziano, J. Michael
Hartline, Jo Ann
Parsons, J. Kellogg
Bearden, James D., III
Crawford, E. David
Goodman, Gary E.
Claudio, Jaime
Winquist, Eric
Cook, Elise D.
Karp, Daniel D.
Walther, Philip
Lieber, Michael M.
Kristal, Alan R.
Darke, Amy K.
Arnold, Kathryn B.
Ganz, Patricia A.
Santella, Regina M.
Albanes, Demetrius
Taylor, Philip R.
Probstfield, Jeffrey L.
Jagpal, T. J.
Crowley, John J.
Meyskens, Frank L., Jr.
Baker, Laurence H.
Coltman, Charles A., Jr.
TI Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other
Cancers The Selenium and Vitamin E Cancer Prevention Trial ( SELECT)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BETA-CAROTENE; CARDIOVASCULAR-DISEASE;
NUTRITIONAL PREVENTION; ALPHA-TOCOPHEROL; BREAST-CANCER; CELL-LINES;
SUPPLEMENTATION; MORTALITY; CARCINOMA
AB Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo- controlled trial ( Selenium and Vitamin E Cancer Prevention Trial [ SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups ( selenium, vitamin E, selenium + vitamin E, and placebo) in a double- blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older ( African American men) or 55 years or older ( all other men), a serum prostate- specific antigen level of 4 ng/ mL or less, and a digital rectal examination not suspicious for prostate cancer.
Interventions Oral selenium ( 200 mu g/d from L- selenomethionine) and matched vitamin E placebo, vitamin E ( 400 IU/ d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
Main Outcome Measures Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow- up was 5.46 years ( range, 4.17- 7.33 years). Hazard ratios ( 99% confidence intervals [ CIs]) for prostate cancer were 1.13 ( 99% CI, 0.95- 1.35; n= 473) for vitamin E, 1.04 ( 99% CI, 0.87- 1.24; n= 432) for selenium, and 1.05 ( 99% CI, 0.88- 1.25; n= 437) for selenium + vitamin E vs 1.00 ( n= 416) for placebo. There were no significant differences ( all P >. 15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group ( P=. 06) and type 2 diabetes mellitus in the selenium group ( relative risk, 1.07; 99% CI, 0.94- 1.22; P=. 16) but not in the selenium + vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
Trial Registration clinicaltrials. gov identifier: NCT00006392.
C1 [Lippman, Scott M.; Karp, Daniel D.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Div Canc Med,Unit 432, Houston, TX 77030 USA.
[Lippman, Scott M.; Cook, Elise D.] Univ Texas Houston, MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Klein, Eric A.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Goodman, Phyllis J.; Hartline, Jo Ann; Darke, Amy K.; Arnold, Kathryn B.; Crowley, John J.] SW Oncol Grp, Ctr Stat, Seattle, WA USA.
[Lucia, M. Scott] Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO USA.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Div Urol Oncol, Denver, CO USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX USA.
[Coltman, Charles A., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hematol, San Antonio, TX USA.
[Coltman, Charles A., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Oncol, San Antonio, TX USA.
[Ford, Leslie G.; Parnes, Howard L.; Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Albanes, Demetrius; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gaziano, J. Michael] Boston VA Healthcare Ctr, Vet Affairs Cooperat Studies Program, Boston, MA USA.
[Gaziano, J. Michael] Boston VA Healthcare Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Parsons, J. Kellogg] Moores Canc Ctr, La Jolla, CA USA.
[Bearden, James D., III] Upstate Carolina CCOP, Spartanburg, SC USA.
[Goodman, Phyllis J.] Swedish Canc Inst, Div Hematol & Oncol, Seattle, WA USA.
[Claudio, Jaime] Altamira Family Med, Rio Piedras, PR USA.
[Winquist, Eric] London Hlth Sci Ctr, London Reg Canc Program, London, ON, Canada.
[Walther, Philip] Duke Univ, Med Ctr, Dept Urol Surg, Durham, NC USA.
[Lieber, Michael M.] Mayo Clin, Dept Urol, Rochester, MN USA.
[Kristal, Alan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Probstfield, Jeffrey L.] Univ Washington, Dept Med & Cardiol, Seattle, WA 98195 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
[Santella, Regina M.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Jagpal, T. J.] Univ British Columbia, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V5Z 1M9, Canada.
[Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA.
[Baker, Laurence H.] Univ Michigan, Div Hematol & Oncol, Ann Arbor, MI 48109 USA.
[Baker, Laurence H.; Coltman, Charles A., Jr.] SW Oncol Grp, Ann Arbor, MI USA.
RP Lippman, SM (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Div Canc Med,Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM slippman@mdanderson.org; kleine@ccf.org
RI Albanes, Demetrius/B-9749-2015;
OI Kristal, Alan/0000-0002-7329-1617
FU Public Health Service Cooperative Agreement [CA37429]; National Cancer
Institute; National Institutes of Health; Department of Health and Human
Services; National Center for Complementary and Alternative Medicine
FX This work was supported in part by Public Health Service Cooperative
Agreement grant CA37429 awarded by the National Cancer Institute,
National Institutes of Health, Department of Health and Human Services,
and in part by the National Center for Complementary and Alternative
Medicine (National Institutes of Health). Study agents and packaging
were provided by Perrigo Company ( Allegan, Michigan), Sabinsa
Corporation ( Piscataway, NewJersey), Tishcon Corporation (Westbury, New
York), and DSM Nutritional Products Inc ( Parsipanny, New Jersey).
NR 48
TC 976
Z9 1008
U1 7
U2 113
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 7
PY 2009
VL 301
IS 1
BP 39
EP 51
DI 10.1001/jama.2008.864
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 391FY
UT WOS:000262220400019
PM 19066370
ER
PT J
AU Weaver, FM
Follett, K
Stern, M
Hur, K
Harris, C
Marks, WJ
Rothlind, J
Sagher, O
Reda, D
Moy, CS
Pahwa, R
Burchiel, K
Hogarth, P
Lai, EC
Duda, JE
Holloway, K
Samii, A
Horn, S
Bronstein, J
Stoner, G
Heemskerk, J
Huang, GD
AF Weaver, Frances M.
Follett, Kenneth
Stern, Matthew
Hur, Kwan
Harris, Crystal
Marks, William J., Jr.
Rothlind, Johannes
Sagher, Oren
Reda, Domenic
Moy, Claudia S.
Pahwa, Rajesh
Burchiel, Kim
Hogarth, Penelope
Lai, Eugene C.
Duda, John E.
Holloway, Kathryn
Samii, Ali
Horn, Stacy
Bronstein, Jeff
Stoner, Gatana
Heemskerk, Jill
Huang, Grant D.
CA CSP 468 Study Grp
TI Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients
With Advanced Parkinson Disease A Randomized Controlled Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID QUALITY-OF-LIFE; SUBTHALAMIC STIMULATION; MOTOR FLUCTUATIONS; ADVERSE
EVENTS; FOLLOW-UP; MULTICENTER; NUCLEUS; METAANALYSIS; VALIDATION
AB Context Deep brain stimulation is an accepted treatment for advanced Parkinson disease ( PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.
Objective To compare 6- month outcomes for patients with PD who received deep brain stimulation or best medical therapy.
Design, Setting, and Patients Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age ( < 70 years vs >= 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD ( Hoehn and Yahr stage >= 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6- month follow- up visit occurred in May 2006.
Intervention Bilateral deep brain stimulation of the subthalamic nucleus ( n= 60) or globus pallidus ( n= 61). Patients receiving best medical therapy ( n= 134) were actively managed by movement disorder neurologists.
Main Outcome Measures The primary outcome was time spent in the "on" state ( good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.
Results Patients who received deep brain stimulation gained a mean of 4.6 h/ d of on time without troubling dyskinesia compared with 0 h/ d for patients who received best medical therapy ( between group mean difference, 4.5 h/ d [ 95% CI, 3.7- 5.4 h/ d]; P <. 001). Motor function improved significantly ( P <. 001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements ( >= 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality- of- life scores ( P <. 001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients ( P <. 001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.
Conclusion In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.
Trial Registration clinicaltrials. gov Identifier: NCT00056563.
C1 [Weaver, Frances M.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA.
[Hur, Kwan; Reda, Domenic] Edward Hines Jr VA Hosp, Cooperat Studies Coordinating Ctr, Hines, IL 60141 USA.
[Weaver, Frances M.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
[Follett, Kenneth] Univ Nebraska, Dept Neurosurg, Omaha, NE 68182 USA.
[Stern, Matthew; Duda, John E.; Horn, Stacy] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA.
[Stern, Matthew; Duda, John E.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Harris, Crystal] Clin Res Pharm, VA Cooperat Studies Program, Albuquerque, NM USA.
[Marks, William J., Jr.; Rothlind, Johannes] San Francisco VA Med Ctr, San Francisco, CA USA.
[Marks, William J., Jr.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Rothlind, Johannes] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Sagher, Oren] Univ Michigan, Med Ctr, Dept Neurosurg, Ann Arbor, MI 48109 USA.
[Moy, Claudia S.; Heemskerk, Jill] NINDS, Rockville, MD USA.
[Pahwa, Rajesh] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA.
[Burchiel, Kim] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA.
[Hogarth, Penelope] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Lai, Eugene C.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Lai, Eugene C.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Holloway, Kathryn] Richmond VA Med Ctr, Richmond, VA USA.
[Holloway, Kathryn] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA USA.
[Samii, Ali] Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bronstein, Jeff] W Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Stoner, Gatana] Univ Iowa Health Care, Dept Neurosurg, Iowa City, IA USA.
[Huang, Grant D.] VA Off Res & Dev, Dept Vet Affairs, Cooperat Studies Program Cent Off, Washington, DC USA.
RP Weaver, FM (reprint author), Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA.
EM Frances.Weaver@va.gov
FU The Cooperative Studies Program of the Department of Veterans Affairs
Office of Research and Development; National Institute of Neurological
Disorders and Stroke; Medtronic Neuromodulation
FX The Cooperative Studies Program of the Department of Veterans Affairs
Office of Research and Development, the National Institute of
Neurological Disorders and Stroke, and Medtronic Neuromodulation
provided financial support for this study.
NR 31
TC 542
Z9 557
U1 7
U2 50
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 7
PY 2009
VL 301
IS 1
BP 63
EP 73
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 391FY
UT WOS:000262220400021
PM 19126811
ER
PT J
AU Albanes, D
AF Albanes, Demetrius
TI Vitamin Supplements and Cancer Prevention: Where Do Randomized
Controlled Trials Stand?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID BETA-CAROTENE; LUNG-CANCER; CARDIOVASCULAR-DISEASE; COMBINATION; HEALTH;
RISK
C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Hlth,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 3044, Bethesda, MD 20892 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015
NR 13
TC 10
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN 7
PY 2009
VL 101
IS 1
BP 2
EP 3
DI 10.1093/jnci/djn453
PG 2
WC Oncology
SC Oncology
GA 392WS
UT WOS:000262333500003
PM 19116387
ER
PT J
AU Martin, B
Pearson, M
Brenneman, R
Golden, E
Wood, W
Prabhu, V
Becker, KG
Mattson, MP
Maudsley, S
AF Martin, Bronwen
Pearson, Michele
Brenneman, Randall
Golden, Erin
Wood, William, III
Prabhu, Vinayakumar
Becker, Kevin G.
Mattson, Mark P.
Maudsley, Stuart
TI Gonadal Transcriptome Alterations in Response to Dietary Energy Intake:
Sensing the Reproductive Environment
SO PLOS ONE
LA English
DT Article
AB Reproductive capacity and nutritional input are tightly linked and animals' specific responses to alterations in their physical environment and food availability are crucial to ensuring sustainability of that species. We have assessed how alterations in dietary energy intake (both reductions and excess), as well as in food availability, via intermittent fasting (IF), affect the gonadal transcriptome of both male and female rats. Starting at four months of age, male and female rats were subjected to a 20% or 40% caloric restriction (CR) dietary regime, every other day feeding (IF) or a high fat-high glucose (HFG) diet for six months. The transcriptional activity of the gonadal response to these variations in dietary energy intake was assessed at the individual gene level as well as at the parametric functional level. At the individual gene level, the females showed a higher degree of coherency in gonadal gene alterations to CR than the males. The gonadal transcriptional and hormonal response to IF was also significantly different between the male and female rats. The number of genes significantly regulated by IF in male animals was almost 5 times greater than in the females. These IF males also showed the highest testosterone to estrogen ratio in their plasma. Our data show that at the level of gonadal gene responses, the male rats on the IF regime adapt to their environment in a manner that is expected to increase the probability of eventual fertilization of females that the males predict are likely to be sub-fertile due to their perception of a food deficient environment.
C1 [Martin, Bronwen; Pearson, Michele; Brenneman, Randall; Golden, Erin; Mattson, Mark P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
[Wood, William, III; Prabhu, Vinayakumar; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Baltimore, MD USA.
[Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Baltimore, MD USA.
RP Martin, B (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA.
EM maudsleyst@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Becker, Kevin/0000-0002-6794-6656
FU Intramural Research Program of the National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 54
TC 23
Z9 23
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 JAN 7
PY 2009
VL 4
IS 1
AR e4146
DI 10.1371/journal.pone.0004146
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437FX
UT WOS:000265473300011
PM 19127293
ER
PT J
AU Spearman, P
Kalams, S
Elizaga, M
Metch, B
Chiu, YL
Allen, M
Weinhold, KJ
Ferrari, G
Parker, SD
McElrath, MJ
Frey, SE
Fuchs, JD
Keefer, MC
Lubeck, MD
Egan, M
Braun, R
Eldridge, JH
Haynes, BF
Corey, L
AF Spearman, Paul
Kalams, Spyros
Elizaga, Marnie
Metch, Barbara
Chiu, Ya-Lin
Allen, Mary
Weinhold, Kent J.
Ferrari, Guido
Parker, Scott D.
McElrath, M. Juliana
Frey, Sharon E.
Fuchs, Jonathan D.
Keefer, Michael C.
Lubeck, Michael D.
Egan, Michael
Braun, Ralph
Eldridge, John H.
Haynes, Barton F.
Corey, Lawrence
CA NIAID HIV Vaccine Trials Network
TI Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV
with or without GM-CSF in a phase I trial
SO VACCINE
LA English
DT Article
DE HIV vaccine; Multiepitope peptide; GM-CSF; CD8+cytotoxic T cells;
Anti-GM-CSF antibody
ID COLONY-STIMULATING FACTOR; T-CELL RESPONSES; IMMUNE-RESPONSES; DENDRITIC
CELLS; RHESUS-MONKEYS; VIRUS-VACCINE; DNA VACCINE; ADJUVANT; PROTECTION;
MELANOMA
AB There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Spearman, Paul] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
[Kalams, Spyros] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Elizaga, Marnie; Metch, Barbara; Chiu, Ya-Lin; McElrath, M. Juliana; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Allen, Mary] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Weinhold, Kent J.; Ferrari, Guido; Haynes, Barton F.] Duke Univ, Sch Med, Durham, NC USA.
[Parker, Scott D.] Univ Alabama, Sch Med, Birmingham, AL USA.
[Frey, Sharon E.] St Louis Univ, St Louis, MO 63103 USA.
[Fuchs, Jonathan D.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Keefer, Michael C.] Univ Rochester, Sch Med, Rochester, NY USA.
[Lubeck, Michael D.; Egan, Michael; Braun, Ralph; Eldridge, John H.] Wyeth Vaccines Res, Pearl River, NY USA.
RP Spearman, P (reprint author), Emory Univ, Sch Med, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA.
EM paul.spearman@emory.edu
RI Ferrari, Guido/A-6088-2015;
OI Allen, Mary/0000-0001-8163-0714
FU NIAID NIH HHS [U01 AI069418, U01 AI069418-03, U01 AI047985, U01
AI047985-05]
NR 38
TC 38
Z9 43
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JAN 7
PY 2009
VL 27
IS 2
BP 243
EP 249
DI 10.1016/j.vaccine.2008.10.051
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 399DM
UT WOS:000262780600013
PM 18996425
ER
PT J
AU Baid, SK
Lai, EW
Wesley, RA
Ling, A
Timmers, HJLM
Adams, KT
Kozupa, A
Pacak, K
AF Baid, Smita K.
Lai, Edwin W.
Wesley, Robert A.
Ling, Alex
Timmers, Henri J. L. M.
Adams, Karen T.
Kozupa, Anna
Pacak, Karel
TI Brief Communication: Radiographic Contrast Infusion and Catecholamine
Release in Patients With Pheochromocytoma
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
AB Background: Contrast-enhanced computed tomography (CT) is useful for localizing pheochromocytoma. However, in patients with suspected pheochromocytoma, CT is often canceled or not performed because of the strong belief that intravenous contrast may induce hypertensive crisis.
Objective: To examine whether intravenous low-osmolar contrast administration during CT induces catecholamine release that increases blood pressure or heart rate.
Design: Prospective study.
Setting: Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland.
Participants: 22 patients with pheochromocytoma (15 nonadrenal and 7 adrenal) and 8 unmatched control participants without pheochromocytoma.
Measurements: Plasma catecholamine levels, blood pressure, and heart rate.
Results: Plasma catecholamine levels within and between groups did not significantly differ before and after intravenous administration of low-osmolar CT contrast. Patients with pheochromocytoma experienced a clinically and statistically significant increase in diastolic blood pressure that was not accompanied by corresponding increases in plasma catecholamine levels. The difference became non -statistically significant after adjustment for use of alpha-and beta-blockers.
Limitation: The study lacked a placebo group, and the sample was relatively small.
Conclusion: Intravenous low-osmolar contrast-enhanced CT can safely be used in patients with pheochromocytoma who are not receiving alpha-or beta-blockers.
C1 [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Adult Endocrinol Program, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Adult Endocrinol Program, Sect Med Neuroendocrinol, NIH, Bldg 10,CRC,Room 1E-1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and
Development; National Institutes of Health
FX Eunice Kennedy Shriver National Institute of Child Health and
Development, National Institutes of Health.
NR 5
TC 12
Z9 12
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
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JAN 6
PY 2009
VL 150
IS 1
BP 27
EP W6
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 397IC
UT WOS:000262655100004
PM 19124817
ER
PT J
AU Goldstein, DS
Sharabi, Y
AF Goldstein, David S.
Sharabi, Yehonatan
TI Neurogenic Orthostatic Hypotension A Pathophysiological Approach
SO CIRCULATION
LA English
DT Review
DE hypotension; nervous system, sympathetic; norepinephrine; orthostatic
hypotension; tomography
ID MULTIPLE SYSTEM ATROPHY; CARDIAC SYMPATHETIC DENERVATION; AUTONOMIC
FAILURE; BLOOD-PRESSURE; PARKINSONS-DISEASE; PLASMA-LEVELS;
NOREPINEPHRINE; HYPERTENSION; CATECHOLS; AUTOIMMUNE
C1 [Goldstein, David S.; Sharabi, Yehonatan] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD USA.
[Sharabi, Yehonatan] Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel.
[Sharabi, Yehonatan] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
RP Goldstein, DS (reprint author), Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU National Institutes of Health
FX The research was supported by the intramural research program of the
National Institutes of Health.
NR 49
TC 51
Z9 52
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JAN 6
PY 2009
VL 119
IS 1
BP 139
EP 146
DI 10.1161/CIRCULATIONAHA.108.805887
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 390YT
UT WOS:000262200300020
PM 19124673
ER
EF