FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Tabak, LA
AF Tabak, Lawrence A.
TI The role of mucin-type O-glycans in eukaryotic development
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE Mucin-type O-glycosylation; Mucins; Glycosyltransferases;
UDP-GalNAc:polypeptide; N-acetylgalactosaminyltransferases; O-glycans
ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; PORCINE SUBMAXILLARY
MUCIN; UDP-GALNAC; IGA NEPHROPATHY; DROSOPHILA-MELANOGASTER; LINKED
GLYCOSYLATION; SALIVARY MUCINS; NERVOUS-SYSTEM; MOUSE EMBRYOS; C1GALT1
GENE
AB Newly emerging genetic studies have revealed that a subset of the family of glycosyltransferases responsible for the formation of mucin-typeOglycans is essential for normal development. As additional genetic, biochemical and physical tools are developed to interrogate the complex structure and surface location of this under-studied class of carbohydrate, no doubt additional roles will be elucidated. Published by Elsevier Ltd.
C1 NIDDKD, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
RP Tabak, LA (reprint author), NIDDKD, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
EM tabakl@mail.nih.gov
FU NIDDK, NIH
FX Original research from my laboratory is supported by funds of the
intramural program of NIDDK, NIH. The helpful comments of Dr. Kelly Ten
Hagen and the members of my laboratory are greatly appreciated.
NR 97
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U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD AUG
PY 2010
VL 21
IS 6
BP 616
EP 621
DI 10.1016/j.semcdb.2010.02.001
PG 6
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 634TK
UT WOS:000280608100012
PM 20144722
ER
PT J
AU Kramer, KL
AF Kramer, Kenneth L.
TI Specific sides to multifaceted glycosaminoglycans are observed in
embryonic development
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE Heparan sulfate; Chondroitin sulfate; Keratan sulfate; Hyaluronan;
Glycosaminoglycan
ID FIBROBLAST-GROWTH-FACTOR; HEPARAN-SULFATE BIOSYNTHESIS; OVERSULFATED
CHONDROITIN SULFATE; GLYPICAN DALLY-LIKE; SPINAL-CORD-INJURY;
CAENORHABDITIS-ELEGANS; DERMATAN SULFATE; HSPG SYNTHESIS; AXON GUIDANCE;
CELL-DIVISION
AB Ubiquitously found in the extracellular matrix and attached to the surface of most cells, glycosaminoglycans (GAGs) mediate many intercellular interactions. Originally described in 1889 as the primary carbohydrate in cartilage and then in 1916 as a coagulation inhibitor from liver, various GAGs have since been identified as key regulators of normal physiology. GAGs are critical mediators of differentiation, migration, tissue morphogenesis, and organogenesis during embryonic development. While GAGs are simple polysaccharide chains, many GAGs acquire a considerable degree of complexity by extensive modifications involving sulfation and epimerization. Embryos that lack specific GAG modifying enzymes have distinct developmental defects, illuminating the importance of GAG complexity. Revealing how these complex molecules specifically function in the embryo has often required additional approaches, the results of which suggest that GAG modifications might instructively mediate embryonic development. Published by Elsevier Ltd.
C1 NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Kramer, KL (reprint author), NHLBI, Genet & Dev Biol Ctr, NIH, 10 Ctr Dr Bldg 10,Rm 6C103, Bethesda, MD 20892 USA.
EM kramerk2@mail.nih.gov
FU NHLBI, NIH
FX I appreciated the constructive comments from Keji Zhao, Matt Hoffman,
Charley Tharp, Kathy Chu, and Ashok Srinivasan. Research in my
laboratory is funded by the intramural program of NHLBI, NIH. The
content is solely the responsibility of the author and does not
necessarily represent the official views of the National Heart, Lung,
and Blood Institute or the National Institutes of Health.
NR 119
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U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD AUG
PY 2010
VL 21
IS 6
BP 631
EP 637
DI 10.1016/j.semcdb.2010.06.002
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 634TK
UT WOS:000280608100014
PM 20599516
ER
PT J
AU Love, DC
Krause, MW
Hanover, JA
AF Love, Dona C.
Krause, Michael W.
Hanover, John A.
TI O-GlcNAc cycling: Emerging roles in development and epigenetics
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE O-GlcNAc; Transcription; Polycomb group proteins; Development; Stem
cells
ID RNA-POLYMERASE-II; GLUCOSE-INDUCED DESENSITIZATION; POLYCOMB-GROUP GENE;
CAENORHABDITIS-ELEGANS; X-CHROMOSOME; TRANSCRIPTIONAL REGULATION;
TETRATRICOPEPTIDE REPEATS; HISTONE METHYLTRANSFERASE;
SUBSTRATE-SPECIFICITY; DOSAGE COMPENSATION
AB The nutrient-sensing hexosamine signaling pathway modulates the levels of O-linked N-acetylglucosamine (O-GlcNAc) on key targets impacting cellular signaling, protein turnover and gene expression. O-GlcNAc cycling may be deregulated in neurodegenerative disease, cancer, and diabetes. Studies in model organisms demonstrate that the O-GlcNAc transferase (OGT/Sxc) is essential for Polycomb group (PcG) repression of the homeotic genes, clusters of genes responsible for the adult body plan. Surprisingly, from flies to man, the O-GlcNAcase (OGA, MGEA5) gene is embedded within the NK cluster, the most evolutionarily ancient of three homeobox gene clusters regulated by PcG repression. PcG repression also plays a key role in maintaining stem cell identity, recruiting the DNA methyltransferase machinery for imprinting, and in X-chromosome inactivation. Intriguingly, the Ogt gene resides near the Xist locus in vertebrates and is subject to regulation by PcG-dependent X-inactivation. OGT is also an enzymatic component of the human dosage compensation complex. These 'evo-devo' relationships linking O-GlcNAc cycling to higher order chromatin structure provide insights into how nutrient availability may influence the epigenetic regulation of gene expression. O-GlcNAc cycling at promoters and PcG repression represent concrete mechanisms by which nutritional information may be transmitted across generations in the intra-uterine environment. Thus, the nutrient-sensing hexosamine signaling pathway may be a key contributor to the metabolic deregulation resulting from prenatal exposure to famine, or the 'vicious cycle' observed in children of mothers with type-2 diabetes and metabolic disease. Published by Elsevier Ltd.
C1 [Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bldg 8 Rm B127,8 Ctr Dr MSC 0850, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
OI Krause, Michael/0000-0001-6127-3940
FU Intramural NIH HHS [ZIA DK060101-03]
NR 77
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U1 2
U2 25
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD AUG
PY 2010
VL 21
IS 6
BP 646
EP 654
DI 10.1016/j.semcdb.2010.05.001
PG 9
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 634TK
UT WOS:000280608100016
PM 20488252
ER
PT J
AU Hayes, SM
Laird, RM
Love, PE
AF Hayes, Sandra M.
Laird, Renee M.
Love, Paul E.
TI Beyond alpha beta/gamma delta lineage commitment: TCR signal strength
regulates gamma delta T cell maturation and effector fate
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE T cell development; Signal transduction; gamma delta T cell receptor;
Effector function
ID INTERFERON-GAMMA; IGE PRODUCTION; RECEPTOR; BETA; THYMOCYTES;
REPERTOIRE; SELECTION; THYMUS; PRE; DIFFERENTIATION
AB Signaling by the gamma delta T cell receptor (TCR) is required not only for alpha beta/gamma delta lineage commitment but also to activate and elicit effector functions in mature gamma delta T cells. Notably, at both of these stages, the signal delivered by the gamma delta TCR is more robust than the one delivered by either the preTCR or the alpha beta TCR. Recent studies now provide evidence that signaling by the gamma delta TCR is also required at other stages during gamma delta T cell development. Remarkably, the strength of the gamma delta TCR signal also plays a role at these other stages, as evidenced by the findings that genetic manipulation of gamma delta TCR signal strength affects gamma delta T cell maturation and effector fate. In this review, we discuss how a strong TCR signal is a recurring theme in gamma delta T cell development and activation. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Hayes, Sandra M.; Laird, Renee M.] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY 13210 USA.
[Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Dev Biol, Program Genom Differentiat, Bethesda, MD USA.
RP Hayes, SM (reprint author), SUNY Upstate Med Univ, Dept Microbiol & Immunol, 750 E Adams St,2220 Weiskotten Hall, Syracuse, NY 13210 USA.
EM hayessa@upstate.edu
FU Hendricks Fund for Medical Research; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This research was supported in part by the Hendricks Fund for Medical
Research (to S.M.H.) and the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH (to P.E.L.).
NR 53
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U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD AUG
PY 2010
VL 22
IS 4
BP 247
EP 251
DI 10.1016/j.smim.2010.04.006
PG 5
WC Immunology
SC Immunology
GA 631XG
UT WOS:000280383400009
PM 20452783
ER
PT J
AU Wynn, TA
Barron, L
AF Wynn, Thomas A.
Barron, Luke
TI Macrophages: Master Regulators of Inflammation and Fibrosis
SO SEMINARS IN LIVER DISEASE
LA English
DT Review
DE Fibrosis; inflammation; collagen; wound healing; stellate cell;
myofibroblasts; interleukin-13; transforming growth factor beta; tumor
necrosis factor; interleukin-1; interleukin-17; arginase; Relm-alpha;
chitinase
ID ALTERNATIVELY ACTIVATED MACROPHAGES; GROWTH-FACTOR-BETA; INDUCED
PULMONARY-FIBROSIS; HEPATIC STELLATE CELLS; NITRIC-OXIDE SYNTHASE;
CD4(+) T-CELLS; OSTEOPONTIN-DEFICIENT MICE; GENE-EXPRESSION PROFILES;
ANTIGEN-PRESENTING CELLS; INNATE IMMUNE-RESPONSE
AB Macrophages are found in close proximity with collagen-producing myofibroblasts and indisputably play a key role in fibrosis. They produce profibrotic mediators that directly activate fibroblasts, including transforming growth factor-beta 1 and platelet-derived growth factor, and control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. Macrophages also regulate fibrogenesis by secreting chemokines that recruit fibroblasts and other inflammatory cells. With their potential to act in both a pro- and antifibrotic capacity, as well as their ability to regulate the activation of resident and recruited myofibroblasts, macrophages and the factors they express are integrated into all stages of the fibrotic process. These various, and sometimes opposing, functions may be performed by distinct macrophage subpopulations, the identification of which is a growing focus of fibrosis research. Although collagen-secreting myofibroblasts once were thought of as the master "producers" of fibrosis, this review will illustrate how macrophages function as the master "regulators" of fibrosis.
C1 [Wynn, Thomas A.; Barron, Luke] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011
FU Intramural NIH HHS [ZIA AI000829-12, ZIA AI001019-03]
NR 175
TC 370
Z9 383
U1 7
U2 82
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD AUG
PY 2010
VL 30
IS 3
BP 245
EP 257
DI 10.1055/s-0030-1255354
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 629KK
UT WOS:000280196600005
PM 20665377
ER
PT J
AU Dunn, BK
Greenwald, P
AF Dunn, Barbara K.
Greenwald, Peter
TI Cancer Prevention II: Introduction
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; DIETARY MODIFICATION TRIAL; VITAMIN-D
SUPPLEMENTATION; INVASIVE BREAST-CANCER; POSTMENOPAUSAL WOMEN;
COLORECTAL-CANCER; RISK; TAMOXIFEN; INFECTION; ESTROGEN
C1 [Greenwald, Peter] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Greenwald, P (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd,Room 2040,MSC 7309, Bethesda, MD 20892 USA.
EM Peter.Greenwald@nih.hhs.gov
NR 28
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Z9 1
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 321
EP 326
DI 10.1053/j.seminoncol.2010.06.016
PG 6
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400003
PM 20816502
ER
PT J
AU Steele, VE
Lubet, RA
AF Steele, Vernon E.
Lubet, Ronald A.
TI The Use of Animal Models for Cancer Chemoprevention Drug Development
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID URINARY-BLADDER CANCERS; ABERRANT CRYPT FOCI; INDUCED LUNG-TUMORS;
LOW-DOSE ASPIRIN; MAMMARY CARCINOGENESIS; MOUSE MODEL; COLON-CANCER; A/J
MICE; ALPHA-DIFLUOROMETHYLORNITHINE; CYCLOOXYGENASE-2 INHIBITOR
C1 [Steele, Vernon E.] NCI, DCP, NIH, Chemoprevent Agent Dev Res Grp, Rockville, MD 20852 USA.
RP Steele, VE (reprint author), NCI, DCP, NIH, Chemoprevent Agent Dev Res Grp, EPN Room 2118,MSC 7322,6130 Execut Blvd, Rockville, MD 20852 USA.
EM vsly@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 83
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Z9 18
U1 0
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 327
EP 338
DI 10.1053/j.seminoncol.2010.05.010
PG 12
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400004
PM 20816503
ER
PT J
AU Umar, A
Della'Zanna, G
Lubet, R
AF Umar, Asad
Della'Zanna, Gary
Lubet, Ronald
TI Further Thoughts on Preclinical Animal Models for Cancer Prevention:
When Is It Best to Start Treatment? What Are Potential Histopathologic
Endpoints?
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID SPORADIC COLORECTAL ADENOMAS; URINARY-BLADDER; COLON-CANCER;
CHEMOPREVENTIVE EFFICACY; MAMMARY CANCERS; PROSTATE-CANCER;
BREAST-CANCER; LUNG-CANCER; CARCINOGENESIS; TRIAL
C1 [Umar, Asad; Della'Zanna, Gary] NCI, Canc Prevent Div, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA.
[Lubet, Ronald] NCI, Canc Prevent Div, Chemoprevent Agent Dev Program, Bethesda, MD 20892 USA.
RP Lubet, R (reprint author), 6130 Execut Blvd,EPN2141, Rockville, MD 20852 USA.
EM lubetr@mail.nih.gov
NR 31
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U1 1
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 339
EP 344
DI 10.1053/j.seminoncol.2010.07.001
PG 6
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400005
PM 20816504
ER
PT J
AU Johnson, KA
Brown, PH
AF Johnson, Karen A.
Brown, Powel H.
TI Drug Development for Cancer Chemoprevention: Focus on Molecular Targets
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID ADVANCED BREAST-CANCER; SERVICES-TASK-FORCE; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; SPORADIC COLORECTAL ADENOMAS; SURGICAL ADJUVANT
BREAST; GREEN TEA CATECHINS; BOWEL PROJECT P-1; LOW-DOSE ASPIRIN;
POSTMENOPAUSAL WOMEN; PROSTATE-CANCER
C1 [Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Johnson, Karen A.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Brown, PH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
EM phbrown@mdanderson.org
NR 112
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U1 1
U2 23
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 345
EP 358
DI 10.1053/j.seminoncol.2010.05.012
PG 14
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400006
PM 20816505
ER
PT J
AU Szabo, E
AF Szabo, Eva
TI Phase II Cancer Prevention Clinical Trials
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID CARCINOMA IN-SITU; BREAST-CANCER; LUNG-CANCER; INTRAEPITHELIAL
NEOPLASIA; CHEMOPREVENTION TRIAL; BRONCHIAL EPITHELIUM; COLORECTAL
ADENOMAS; RANDOMIZED-TRIAL; BETA-CAROTENE; FOLLOW-UP
C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA.
EM szaboe@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 43
TC 2
Z9 3
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 359
EP 366
DI 10.1053/j.seminoncol.2010.06.015
PG 8
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400007
PM 20816506
ER
PT J
AU Arun, B
Dunn, BK
Ford, LG
Ryan, A
AF Arun, Banu
Dunn, Barbara K.
Ford, Leslie G.
Ryan, Anne
TI Breast Cancer Prevention Trials: Large and Small Trials
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID SURGICAL ADJUVANT BREAST; AROMATASE INHIBITOR EXEMESTANE; STAR P-2
TRIAL; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; CHEMOPREVENTION TRIAL;
BOWEL PROJECT; OVARIECTOMIZED RATS; TAMOXIFEN TREATMENT; COMBINATION
TRIAL
C1 [Arun, Banu] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Dunn, Barbara K.; Ford, Leslie G.; Ryan, Anne] US Natl Canc Inst, Canc Prevent Div, Bethesda, MD USA.
RP Dunn, BK (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,Room 2056, Bethesda, MD 20892 USA.
EM dunnb@mail.nih.gov
NR 85
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Z9 15
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 367
EP 383
DI 10.1053/j.seminoncol.2010.05.004
PG 17
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400008
PM 20816507
ER
PT J
AU Agurs-Collins, T
Dunn, BK
Browne, D
Johnson, KA
Lubet, R
AF Agurs-Collins, Tanya
Dunn, Barbara K.
Browne, Doris
Johnson, Karen A.
Lubet, Ronald
TI Epidemiology of Health Disparities in Relation to the Biology of
Estrogen Receptor-Negative Breast Cancer
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID AFRICAN-AMERICAN WOMEN; RECREATIONAL PHYSICAL-ACTIVITY; BASAL-LIKE
PHENOTYPE; DIETARY FIBER INTAKE; BODY-MASS INDEX; HORMONE-RECEPTOR;
POSTMENOPAUSAL WOMEN; RISK-FACTORS; SOCIOECONOMIC-STATUS; TRANSGENIC
MICE
C1 [Dunn, Barbara K.; Johnson, Karen A.; Lubet, Ronald] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Browne, Doris] Browne & Associates Inc, Washington, DC USA.
RP Dunn, BK (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,Room 2056, Bethesda, MD 20892 USA.
EM dunnb@mail.nih.gov
NR 138
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U1 7
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 384
EP 401
DI 10.1053/j.seminoncol.2010.05.002
PG 18
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400009
PM 20816508
ER
PT J
AU Richmond, E
O'Mara, A
AF Richmond, Ellen
O'Mara, Ann
TI Conducting Chemoprevention Clinical Trials: Challenges and Solutions
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID SPORADIC COLORECTAL ADENOMAS; BARRETTS-ESOPHAGUS; RESEARCH NURSE; CANCER
PREVENTION; BREAST-CANCER; PHASE-III; DYSPLASIA; DIAGNOSIS;
DIFLUOROMETHYLORNITHINE; SULINDAC
C1 [Richmond, Ellen; O'Mara, Ann] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Richmond, E (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd, Bethesda, MD 20892 USA.
EM richmone@mail.nih.gov
NR 22
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 402
EP 406
DI 10.1053/j.seminoncol.2010.05.014
PG 5
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400010
PM 20816509
ER
PT J
AU Calzone, K
Wattendorf, D
Dunn, BK
AF Calzone, Kathleen
Wattendorf, Daniel
Dunn, Barbara K.
TI The Application of Genetics and Genomics to Cancer Prevention
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID NONPOLYPOSIS COLORECTAL-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; POLICY
STATEMENT UPDATE; BREAST-CANCER; FAMILY-HISTORY; LYNCH-SYNDROME;
PROSTATE-CANCER; SUSCEPTIBILITY ALLELES; TAMOXIFEN METABOLISM; ADJUVANT
TAMOXIFEN
C1 [Calzone, Kathleen] NCI, Ctr Canc Res, Genet Branch, NIH, Gaithersburg, MD 20899 USA.
[Calzone, Kathleen; Wattendorf, Daniel] Off Air Force Surgeon Gen, Falls Church, VA USA.
[Dunn, Barbara K.] NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, NIH, Gaithersburg, MD 20899 USA.
RP Calzone, K (reprint author), NCI, Ctr Canc Res, Genet Branch, NIH, 8901 Wisconsin Ave,Bldg 8,Room 5101, Gaithersburg, MD 20899 USA.
EM calzonek@mail.nih.gov
NR 76
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Z9 3
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2010
VL 37
IS 4
BP 407
EP 418
DI 10.1053/j.seminoncol.2010.05.005
PG 12
WC Oncology
SC Oncology
GA 650DW
UT WOS:000281830400011
PM 20816510
ER
PT J
AU Lydon-Rochelle, MT
Cahill, AG
Spong, CY
AF Lydon-Rochelle, Mona T.
Cahill, Alison G.
Spong, Catherine Y.
TI Birth After Previous Cesarean Delivery: Short-Term Maternal Outcomes
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE repeat cesarean section; trial of labor; vaginal birth after cesarean;
cesarean; uterine rupture; pregnancy outcome; NIH Consensus Development
Conference
ID PREVIOUS VAGINAL DELIVERY; UTERINE RUPTURE; INTERPREGNANCY INTERVAL;
INTERDELIVERY INTERVAL; NEONATAL OUTCOMES; LABOR; TRIAL; WOMEN; RISK;
SUCCESS
C1 [Lydon-Rochelle, Mona T.] Cork Univ, Matern Hosp, Natl Perinatal Epidemiol Ctr, Dept Obstet & Gynecol,Univ Coll, Cork, Ireland.
[Lydon-Rochelle, Mona T.] Univ Coll, Sch Med, Dept Epidemiol & Publ Hlth, Cork, Ireland.
[Cahill, Alison G.] Washington Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, St Louis, MO USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
RP Lydon-Rochelle, MT (reprint author), Cork Univ, Matern Hosp, Natl Perinatal Epidemiol Ctr, Dept Obstet & Gynecol,Univ Coll, 5th Floor, Cork, Ireland.
EM M.LydonRochelle@ucc.ie
FU National Perinatal Epidemiology Center, University of College Cork,
Cork, Ireland
FX This work was supported in part by the National Perinatal Epidemiology
Center, University of College Cork, Cork, Ireland.
NR 81
TC 11
Z9 14
U1 1
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD AUG
PY 2010
VL 34
IS 4
BP 249
EP 257
DI 10.1053/j.semperi.2010.03.004
PG 9
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 672EV
UT WOS:000283566700003
PM 20654775
ER
PT J
AU O'Shea, TM
Klebanoff, MA
Signore, C
AF O'Shea, T. Michael
Klebanoff, Mark A.
Signore, Caroline
TI Delivery After Previous Cesarean: Long-Term Outcomes in the Child
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE asthma; brachial plexus injury; cesarean delivery; neonatal
encephalopathy; shoulder dystocia; uterine rupture; vaginal delivery
ID POPULATION-BASED COHORT; PERINATAL RISK-FACTORS; BREAST-FEEDING
INITIATION; BRACHIAL-PLEXUS INJURY; LARGE RANDOMIZED-TRIAL; SHOULDER
DYSTOCIA; NEWBORN ENCEPHALOPATHY; NEONATAL MORBIDITY; ALLERGIC RHINITIS;
UTERINE RUPTURE
C1 [O'Shea, T. Michael] Wake Forest Univ, Dept Pediat Neonatol, Winston Salem, NC 27157 USA.
[Klebanoff, Mark A.; Signore, Caroline] Eunice Kennedy Shriver Natl Inst Human Dev, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP O'Shea, TM (reprint author), Wake Forest Univ, Dept Pediat, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM moshea@wfubmc.edu
FU NIH, NICHD
FX Dr Klebanoff was supported by Intramural Funds from the NIH, NICHD.
NR 95
TC 12
Z9 16
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD AUG
PY 2010
VL 34
IS 4
BP 281
EP 292
DI 10.1053/j.semperi.2010.03.008
PG 12
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 672EV
UT WOS:000283566700007
PM 20654779
ER
PT J
AU Berger, VW
Grant, WC
Vazquez, LF
AF Berger, Vance W.
Grant, William C.
Vazquez, Laura F.
TI Sensitivity designs for preventing bias replication in randomized
clinical trials
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
ID SELECTION BIAS
AB It is common, after a trial is completed, to employ sensitivity analyses to test the extent to which the results depend on various assumptions or conventions. There is a comparable benefit to employing sensitivity designs when planning a trial, so that features that cannot be varied at the analysis stage can instead be varied (e.g., across centres of a multi-centre trial) during the design stage. Design features amenable to such variation include: (1) the specific randomization methods, (2) the duration of follow-up and (3) the use or non-use of a surrogate endpoint as a replacement for a clinical endpoint. Generally, all centres in a given trial, and all trials in a given program, will employ identical protocols. This means that all will be vulnerable to the same types of biases, meaning that a single bias can by itself render all results unreliable. But by varying the randomization techniques, duration and primary endpoint, one can vary also the biases to which the site-specific results are vulnerable. This means that, if a significant result is found, then one can state that either the treatment worked or there were numerous biases (not just one) at play. This of course makes the attribution of the results to the treatments much more plausible and makes the findings much more robust to violations of assumptions.
C1 [Berger, Vance W.] NIH, Bethesda, MD 20892 USA.
[Grant, William C.] James Madison Univ, Dept Econ, Harrisonburg, VA 22807 USA.
[Vazquez, Laura F.] Shepherd Ctr, Marcus Community Bridge Program, Atlanta, GA USA.
RP Berger, VW (reprint author), NIH, Suite 3115,6130 Execut Blvd,MSC-7354, Bethesda, MD 20892 USA.
EM bergerv@mail.nih.gov
NR 8
TC 4
Z9 4
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD AUG
PY 2010
VL 19
IS 4
BP 415
EP 424
DI 10.1177/0962280209359875
PG 10
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA 636MJ
UT WOS:000280739700005
PM 20488837
ER
PT J
AU Watanabe, K
Meyer, MJ
Strizzi, L
Lee, JM
Gonzales, M
Bianco, C
Nagaoka, T
Farid, SS
Margaryan, N
Hendrix, MJC
Vonderhaar, BK
Salomon, DS
AF Watanabe, Kazuhide
Meyer, Matthew J.
Strizzi, Luigi
Lee, Joseph M.
Gonzales, Monica
Bianco, Caterina
Nagaoka, Tadahiro
Farid, Shahram S.
Margaryan, Naira
Hendrix, Mary J. C.
Vonderhaar, Barbara K.
Salomon, David S.
TI Cripto-1 Is a Cell Surface Marker for a Tumorigenic, Undifferentiated
Subpopulation in Human Embryonal Carcinoma Cells
SO STEM CELLS
LA English
DT Article
DE Cripto-1; Embryonal carcinoma; Nanog; Oct4; Pluripotent stem cells;
Tumorigenicity
ID PLURIPOTENT STEM-CELLS; TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; CANCER
CELLS; GROWTH; DIFFERENTIATION; NANOG; HETEROGENEITY; TARGET; PATHWAYS
AB Deregulation of stem cells is associated with the generation and progression of malignant tumors. In addition, genes that are associated with early embryogenesis are frequently expressed in cancer. Cripto-1 (CR-1), a glycosylphosphatidylinositol-linked glycoprotein, is expressed during early embryogenesis and in various human carcinomas. We demonstrated that human embryonal carcinoma (EC) cells are heterogeneous for CR-1 expression and consist of two distinct subpopulations: a CR-1(High) and a CR-1(Low) population. By segregating CR-1(High) and CR-1(Low) populations of NTERA2/D1 EC cells by fluorescence-activated cell sorting, we demonstrated that CR-1(High) cells were more tumorigenic than CR-1(Low) cells by an in vitro tumor sphere assay and by in vivo xenograft formation. The CR-1(High) population was enriched in mRNA expression for the pluripotent embryonic stem (ES) cell genes Oct4, Sox2, and Nanog. CR-1 expression in NTERA2/D1 cells was regulated by a Smad2/3-dependent autocrine loop, by the ES cell-related transcription factors Oct4/Nanog, and partially by the DNA methylation status of the promoter region. These results demonstrate that CR-1 expression is enriched in an undifferentiated, tumorigenic subpopulation and is regulated by key regulators of pluripotent stem cells. STEM CELLS 2010; 28: 1303-1314
C1 [Watanabe, Kazuhide; Meyer, Matthew J.; Lee, Joseph M.; Gonzales, Monica; Bianco, Caterina; Nagaoka, Tadahiro; Vonderhaar, Barbara K.; Salomon, David S.] Northwestern Univ, Feinberg Sch Med, Mammary Biol & Tumorigenesis Lab, Chicago, IL 60611 USA.
[Strizzi, Luigi; Margaryan, Naira; Hendrix, Mary J. C.] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA.
[Farid, Shahram S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Salomon, DS (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, CCR, 37 Convent Dr,Bldg 37,Rm1118B, Bethesda, MD 20892 USA.
EM salomond@mail.nih.gov
OI Nagaoka, Tadahiro/0000-0002-9391-0243
FU NIH, National Cancer Institute, Center for Cancer Research; NIH
[CA59702, CA121205, CA75681]; Eisenberg Research Fund
FX We thank Arnold Mixon for help in cell sorting. This research was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research and NIH Grants CA59702, CA121205,
and CA75681 to Mary J.C. Hendrix and Eisenberg Research Fund to Luigi
Strizzi.
NR 47
TC 24
Z9 25
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD AUG
PY 2010
VL 28
IS 8
BP 1303
EP 1314
DI 10.1002/stem.463
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 646TP
UT WOS:000281566200001
PM 20549704
ER
PT J
AU Mohr, JP
Moskowitz, AJ
Stapf, C
Hartmann, A
Lord, K
Marshall, SM
Mast, H
Moquete, E
Moy, CS
Parides, M
Pile-Spellman, J
Salman, RAS
Weinberg, A
Young, WL
Estevez, A
Kureshi, I
Brisman, JL
AF Mohr, J. P.
Moskowitz, Alan J.
Stapf, Christian
Hartmann, Andreas
Lord, Karen
Marshall, Steven M.
Mast, Henning
Moquete, Ellen
Moy, Claudia Scala
Parides, Michael
Pile-Spellman, John
Salman, Rustam Al-Shahi
Weinberg, Alan
Young, William L.
Estevez, Alejandrina
Kureshi, Inam
Brisman, Jonathan L.
TI The ARUBA Trial Current Status, Future Hopes
SO STROKE
LA English
DT Review
DE arteriovenous malformations; endovascular treatment; neuroradiology;
neurosurgery; radiotherapy; randomized controlled trials
ID BRAIN ARTERIOVENOUS-MALFORMATIONS; INTRACRANIAL VASCULAR MALFORMATIONS;
NATURAL-HISTORY; EXTRACRANIAL ARTERIES; FOLLOW-UP; HEMORRHAGE;
DETERMINANTS; RISK; ENDARTERECTOMY; EMBOLIZATION
AB Background and Purpose-Report on the status of an on-going National Institutes of Neurological Disorders and Stroke (NINDS)-supported clinical trial of management of unbled brain arteriovenous malformations.
Summary of Review-Begun in April 2007 with 3 centers, the trial has grown to 65 centers, and has randomized 124 patients through mid-June 2010 en route to the planned 400. The current literature continues to support the rationale for the trial.
Conclusions-ARUBA is steadily approaching its monthly randomization goals and has already reached the number needed to test the maximum published interventional complication rates against the minimum hemorrhage rates for natural history. (Stroke. 2010; 41: e537-e540.)
C1 [Mohr, J. P.; Lord, Karen; Pile-Spellman, John] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Mohr, J. P.] Doris & Stanley Tananbaum Stroke Ctr, Neurol Inst, New York, NY 10032 USA.
[Moquete, Ellen; Parides, Michael; Weinberg, Alan; Estevez, Alejandrina] Mt Sinai Sch Med, New York, NY USA.
[Stapf, Christian] Hop Lariboisiere, F-75475 Paris, France.
[Hartmann, Andreas] Klinikum Frankfurt Oder, Frankfurt, Germany.
[Lord, Karen; Marshall, Steven M.] Columbia Univ, New York, NY USA.
[Mast, Henning] Klin Im Pk, Zurich, Switzerland.
[Moy, Claudia Scala] NINDS, Bethesda, MD 20892 USA.
[Salman, Rustam Al-Shahi] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Young, William L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kureshi, Inam] Hartford Hosp, Hartford, CT 06115 USA.
Winthrop Univ Hosp, Mineola, NY 11501 USA.
RP Mohr, JP (reprint author), Columbia Univ Coll Phys & Surg, 710 W 168th St, New York, NY 10032 USA.
EM jpm10@columbia.edu
OI Stapf, Christian/0000-0002-3193-1006; Moskowitz,
Alan/0000-0002-4412-9450; Al-Shahi Salman, Rustam/0000-0002-2108-9222
FU Medical Research Council [G108/613]; NINDS NIH HHS [U01 NS051483, U01
NS051483-03]
NR 51
TC 34
Z9 35
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD AUG
PY 2010
VL 41
IS 8
BP E537
EP E540
DI 10.1161/STROKEAHA.110.580274
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 631EZ
UT WOS:000280330700047
PM 20634478
ER
PT J
AU Richtand, NM
Liu, YH
Ahlbrand, R
Sullivan, JR
Newman, AH
McNamara, RK
AF Richtand, Neil M.
Liu, Yanghong
Ahlbrand, Rebecca
Sullivan, Juliana R.
Newman, Amy Hauck
McNamara, Robert K.
TI Dopaminergic Regulation of Dopamine D3 and D3nf Receptor mRNA Expression
SO SYNAPSE
LA English
DT Article
DE dopamine D3 receptor; NGB 2904; D3nf; alternative splicing; amphetamine;
hippocampus; tyrosine hydroxylase; tyrosine 3-monooxygenase
ID SPLICE VARIANT D3NF; BEHAVIORAL SENSITIZATION; CHRONIC-SCHIZOPHRENIA;
INHIBITORY FUNCTION; GENE-EXPRESSION; RELEASE; RAT; AMPHETAMINE; BRAIN;
MICE
AB Dopamine D3 receptors have the highest dopamine affinity of all dopamine receptors, and may thereby regulate dopamine signaling mediated by volume transmission Changes in D3 receptor isoform expression may alter D3 receptor function, however, little is known regarding coordination of D3 isoform expression in response to perturbations in dopaminergic stimulation. To determine the effects of dopamine receptor stimulation and blockade on D3 receptor alternative splicing, we determined D3 and D3nf isoform mRNA expression following treatment with the D3 receptor antagonist NGB 2904, and the indirect dopamine agonist amphetamine. Expression of tyrosine hydroxylase (TH) mRNA, the rate-limiting enzyme in dopamine synthesis, was also determined. The D3/D3nf mRNA expression ratio was increased in ventral striatum, prefrontal cortex, and hippocampus 6 h following D3 antagonist NGB 2904 treatment, and remained persistently elevated at 24 h in hippocampus and substantia nigra/ventral tegmentum. D3 mRNA decreased 65% and D3nf mRNA expression decreased 71% in prefrontal cortex 24 h following amphetamine treatment, however, these changes did not reach statistical significance. TH mRNA expression was unaffected by D3 antagonist NGB 2904, but was elevated by amphetamine in ventral striatum, hippocampus, and prefrontal cortex. These findings provide evidence for an adaptive response to altered D3 receptor stimulation involving changes in D3 receptor alternative splicing. Additionally, these data suggest D3 autoreceptor regulation of dopamine synthesis does not involve regulation of TH mRNA expression Finally, the observation of regulated TH mRNA expression in dopamine terminal fields provides experimental support for the model of local control of mRNA expression in adaptation to synaptic activity. Synapse 64:634-643, 2010. (C)2010 Wiley-Liss, Inc
C1 [Richtand, Neil M.; Liu, Yanghong; Ahlbrand, Rebecca; Sullivan, Juliana R.; McNamara, Robert K.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA.
[Richtand, Neil M.] Cincinnati Vet Affairs Med Ctr, Psychiat Serv, Cincinnati, OH 45220 USA.
[Newman, Amy Hauck] NIDA, Intramural Res Program, Med Chem Sect, Baltimore, MD 21131 USA.
RP Richtand, NM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Albert Sabin Way, Cincinnati, OH 45267 USA.
RI McNamara, Robert/J-4309-2014
FU Department of Veterans Affairs Medical Research Service [NIDA R01 16778,
NIMH R21MH083192]; National Institute of Health
FX Contract grant sponsor Department of Veterans Affairs Medical Research
Service, Contract grant numbers NIDA R01 16778, NIMH R21MH083192.
Contract, grant sponsor NIDA-Intramural Research Program, National
Institute of Health
NR 37
TC 4
Z9 4
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD AUG
PY 2010
VL 64
IS 8
BP 634
EP 643
DI 10.1002/syn.20770
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 621AI
UT WOS:000279545100007
PM 20340170
ER
PT J
AU Ozaki, H
Zoghbi, SS
Hong, J
Verma, A
Pike, VW
Innis, RB
Fujita, M
AF Ozaki, Harushige
Zoghbi, Sami S.
Hong, Jinsoo
Verma, Ajay
Pike, Victor W.
Innis, Robert B.
Fujita, Masahiro
TI In Vivo Binding of Protoporphyrin IX to Rat Translocator Protein Imaged
With Positron Emission Tomography
SO SYNAPSE
LA English
DT Article
DE peripheral benzodiazepine receptor; 5-aminolevulinic acid; porphyria
ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; ERYTHROPOIETIC PROTOPORPHYRIA; 18
KDA; BRAIN; RADIOLIGAND; LIGANDS
AB In vitro experiments have shown that protoporphyrin DC (PPIX) binds to the translocator protein 18 kDa (TSPO), which transports cholesterol across the outer mitochondrial membrane. The purpose of this study was to examine whether binding of PPIX to TSPO can also be detected in vivo using positron emission tomography and [(11)C]PBR28, a radioligand that binds with high affinity and selectivity to TSPO. Rats were injected with a high dose of 5-aminolevulinic acid (ALA, 200 mg/kg i.v), which is a precursor for PPIX. ALA-pretreatment significantly decreased the uptake of [(11)C]PBR28 in TSPO-rich organs such as heart, kidneys, lungs, parotid glands and spleen by 57-80%. As a control experiment, injection of a receptor saturating does of PK 11195, which is selective for TSPO, produced a pattern of displacement similar to that after ALA but with greater magnitude (88-97%). This study provides the first evidence that PPIX binds in vivo to TSPO Although PPIX. at physiological concentrations would likely occupy an insignificant percentage of TSPOs, it does reach high-enough concentrations in porphyria to occupy and have pharmacological effects via this target. Synapse 64:649-653, 2010. (C)2010 Wiley-Liss, Inc
C1 [Ozaki, Harushige; Zoghbi, Sami S.; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Verma, Ajay] Novartis Pharmaceut, VP Neurosci & Ophthalmol, E Hanover, NJ USA.
RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 31,Room B2B37,31 Ctr Dr,MSC 2035, Bethesda, MD 20892 USA.
FU NIMH [Z01-MH-002795-07, Z01-MH-002793-07]
FX Contract grant spansor Intramural Program, NIMH, Contract grant numbers
Z01-MH-002795-07, Z01-MH-002793-07
NR 16
TC 5
Z9 6
U1 1
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD AUG
PY 2010
VL 64
IS 8
BP 649
EP 653
DI 10.1002/syn.20779
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 621AI
UT WOS:000279545100009
PM 20336621
ER
PT J
AU Traverse, JH
Henry, TD
Vaughan, DE
Ellis, SG
Pepine, CJ
Willerson, JT
Zhao, DXM
Simpson, LM
Penn, MS
Byrne, BJ
Perin, EC
Gee, AP
Hatzopoulos, AK
McKenna, DH
Forder, JR
Taylor, DA
Cogle, CR
Baraniuk, S
Olson, RE
Jorgenson, BC
Sayre, SL
Vojvodic, RW
Gordon, DJ
Skarlatos, SI
Moye, LA
Simari, RD
AF Traverse, Jay H.
Henry, Timothy D.
Vaughan, Douglas E.
Ellis, Stephen G.
Pepine, Carl J.
Willerson, James T.
Zhao, David X. M.
Simpson, Lara M.
Penn, Marc S.
Byrne, Barry J.
Perin, Emerson C.
Gee, Adrian P.
Hatzopoulos, Antonis K.
McKenna, David H.
Forder, John R.
Taylor, Doris A.
Cogle, Christopher R.
Baraniuk, Sarah
Olson, Rachel E.
Jorgenson, Beth C.
Sayre, Shelly L.
Vojvodic, Rachel W.
Gordon, David J.
Skarlatos, Sonia I.
Moye, Lemuel A.
Simari, Robert D.
CA CCTRN
TI LateTIME A Phase-II, Randomized, Double-Blinded, Placebo-Controlled,
Pilot Trial Evaluating the Safety and Effect of Administration of Bone
Marrow Mononuclear Cells 2 to 3 Weeks after Acute Myocardial Infarction
SO TEXAS HEART INSTITUTE JOURNAL
LA English
DT Article
DE Apoptosis; bone marrow cells; bone marrow transplantation; cell therapy;
colony-stimulating factors; free radicals; heart failure; infusions,
intra-arterial; inflammation/prevention & control; magnetic resonance
imaging; myocardial infarction/therapy; myocardial ischemia/therapy;
myocardial reperfusion injury; myocytes, cardiac; prospective studies;
regeneration; research design; stem cells; stem cell transplantation;
time factors; ventricular function, left; ventricular remodeling
ID HEMATOPOIETIC STEM-CELLS; TRANSCORONARY TRANSPLANTATION;
ISCHEMIC-MYOCARDIUM; PROGENITOR CELLS; HEART-FAILURE; REGENERATION;
METAANALYSIS; APOPTOSIS; CYTOKINES; FACTOR-1
AB A realistic goal for cardiac cell therapy may be to attenuate left ventricular remodeling following acute myocardial infarction to prevent the development of congestive heart failure. Initial clinical trials of cell therapy have delivered cells 1 to 7 days after acute myocardial infarction. However, many patients at risk of developing congestive heart failure may not be ready for cell delivery at that time-point because of clinical instability or hospitalization at facilities without access to cell therapy Experience with cell delivery 2 to 3 weeks after acute myocardial infarction has not to date been explored in a clinical trial. The objective of the LateTIME study is to evaluate by cardiac magnetic resonance the effect on global and regional left ventricular function, between baseline and 6 months, of a single intracoronary infusion of 150 x 10(6) autologous bone marrow mononuclear cells (compared with placebo) when that infusion is administered 2 to 3 weeks after moderate-to-large acute myocardial infarction. The 5 clinical sites of the Cardiovascular Cell Therapy Research Network (CCTRN) will enroll a total of 87 eligible patients in a 2:1 bone marrow mononuclear cells-to-placebo patient ratio; these 87 will have undergone successful percutaneous coronary intervention of a major coronary artery and have left ventricular ejection fractions <= 0.45 by echocardiography. When the results become available, this study should provide insight into the clinical feasibility and appropriate timing of autologous cell therapy in high-risk patients after acute myocardial infarction and percutaneous coronary intervention. (Tex Heart Mat J 2010;37(4)412-20)
C1 [Moye, Lemuel A.] Univ Texas Houston, Sch Publ Hlth, Dept Biostat, Houston, TX 77030 USA.
[Gee, Adrian P.] Baylor Univ, Sch Med, Waco, TX 76798 USA.
[Ellis, Stephen G.; Penn, Marc S.] Cleveland Clin Fdn, Cleveland, OH USA.
[Simari, Robert D.] Mayo Clin, Rochester, MN 55905 USA.
[Traverse, Jay H.; Henry, Timothy D.; Olson, Rachel E.; Jorgenson, Beth C.] Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN USA.
[Gordon, David J.; Skarlatos, Sonia I.] NHLBI, Bethesda, MD 20892 USA.
[Willerson, James T.; Perin, Emerson C.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA.
[Pepine, Carl J.; Byrne, Barry J.; Forder, John R.; Cogle, Christopher R.] Univ Florida, Sch Med, Gainesville, FL 32611 USA.
[Traverse, Jay H.; Henry, Timothy D.; McKenna, David H.; Taylor, Doris A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Vaughan, Douglas E.; Zhao, David X. M.; Hatzopoulos, Antonis K.] Vanderbilt Univ, Sch Med, Nashville, TN 37235 USA.
RP Moye, LA (reprint author), Univ Texas Houston, Sch Publ Hlth, Dept Biostat, RAS Bldg,1200 Herman Pressler, Houston, TX 77030 USA.
EM Lemuel.A.Moye@uth.tmc.edu
RI Hatzopoulos, Antonis/D-2049-2010; Cogle, Christopher/H-1746-2016
OI Cogle, Christopher/0000-0001-5422-6863
FU NHLBI NIH HHS [N01-HB-37164, N01HB37164, U01 HL087318, U01 HL087318-01]
NR 30
TC 30
Z9 30
U1 1
U2 6
PU TEXAS HEART INST
PI HOUSTON
PA PO BOX 20345, HOUSTON, TX 77225-0345 USA
SN 0730-2347
J9 TEX HEART I J
JI Tex. Heart Inst. J.
PD AUG
PY 2010
VL 37
IS 4
BP 412
EP 420
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 636PX
UT WOS:000280752000004
PM 20844613
ER
PT J
AU Barnes, AJ
Brunet, BR
Choo, RE
Mura, P
Johnson, RE
Jones, HE
Huestis, MA
AF Barnes, Allan J.
Brunet, Bertrand R.
Choo, Robin E.
Mura, Patrick
Johnson, Rolley E.
Jones, Hendree E.
Huestis, Marilyn A.
TI Excretion of Methadone in Sweat of Pregnant Women Throughout Gestation
After Controlled Methadone Administration
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE sweat; methadone; therapeutic drug monitoring; alternative matrix; drug
testing
ID MASS SPECTROMETRY METHOD; ABUSE-TREATMENT PATIENTS; SOLID-PHASE
EXTRACTION; SUBSTANCE-ABUSE; COCAINE USE; ORAL FLUID; METABOLITES;
DISPOSITION; ADDICTS; HEROIN
AB Sweat patches (n = 350) were collected throughout gestation from 29 opioid-dependent pregnant women participating in an outpatient methadone-assisted therapy program. Volunteers provided informed consent to participate in institutional review board-approved protocols. Methadone was eluted from sweat patches with sodium acetate buffer, followed by solid-phase extraction and quantification by gas chromatography mass spectrometry (limit of quantification >= 10 ng/patch). Methadone was present in all weekly patches (n = 311) in concentrations ranging from 10.2 to 12,129.7 nanograms per patch and in 92.3% of short-term patches (n = 39, worn for 12 or 24 hours) in concentrations up to 3303.9 nanograms per patch. Correlation between patch concentrations and total amount of drug administered (r = 0.224), and concentrations and duration of patch wear (r = 0.129) were both weak. Although there were large intra-and intersubject variations in sweat drug concentrations, sweat testing was an effective alternative technique to qualitatively monitor illicit drug use and simultaneously document methadone medication-assisted treatment.
C1 [Barnes, Allan J.; Huestis, Marilyn A.] NIDA, IRP, NIH, Baltimore, MD 21224 USA.
[Brunet, Bertrand R.] Univ Poitiers, Fac Med & Pharm, INSERM, UMR 927, Poitiers, France.
[Choo, Robin E.] Univ Pittsburgh, Dept Nat Sci, Titusville, PA USA.
[Mura, Patrick] Ctr Hosp Reg & Univ Poitiers, Lab Toxicol & Pharmacocinet, Poitiers, France.
[Johnson, Rolley E.; Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Johnson, Rolley E.] Reckitt Benckiser Pharmaceut Inc, Richmond, VA USA.
[Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA.
RP Huestis, MA (reprint author), NIDA, IRP, NIH, 251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse [DA R01 12220, DA R01 12403]; National
Center of Research Resources, National Institutes of Health
[M01RR-02719]
FX Supported by the National Institutes of Health, Intramural Research
Program, National Institute on Drug Abuse and DA R01 12220 and DA R01
12403 from the National Institute on Drug Abuse and M01RR-02719 from the
General Clinical Research Centers Program of the National Center of
Research Resources, National Institutes of Health.
NR 32
TC 6
Z9 6
U1 1
U2 1
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 AUG
PY 2010
VL 32
IS 4
BP 497
EP 503
DI 10.1097/FTD.0b013e3181e44293
PG 7
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 629HH
UT WOS:000280186200017
PM 20592651
ER
PT J
AU Dinse, GE
Peddada, SD
Harris, SF
Elmore, SA
AF Dinse, Gregg E.
Peddada, Shyamal D.
Harris, Shawn F.
Elmore, Susan A.
TI Comparison of NTP Historical Control Tumor Incidence Rates in Female
Harlan Sprague Dawley and Fischer 344/N Rats
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE Fischer 344/N; historical control; multiple testing correction; NTP;
Sprague Dawley; survival adjustment; tumor incidence
ID MODERATE DIETARY RESTRICTION; PROLIFERATIVE RODENT LESIONS; DIOXIN-LIKE
COMPOUNDS; BODY-WEIGHT; SPONTANEOUS NEOPLASMS; PITUITARY-ADENOMAS;
F344/N RATS; B6C3F1 MICE; LONG-TERM; CORN-OIL
AB The National Toxicology Program (NTP) has historically used Fischer 344/N (F344/N) rats for the majority of its bioassays. Recently the NTP began using the Harlan Sprague Dawley (SD) as the primary rat model for NTP studies. The NTP had previously used female SD rats in nine bioassays. This article compares historical control (HC) tumor incidence rates from these nine SD rat studies with HC tumor rates from matched NTP F344/N rat bioassays to identify similarities and differences. Matching on sex, laboratory, diet, and route led to nine comparable F344/N rat studies. Our analyses revealed statistically significant strain differences, with female SD rats having lower incidence rates for clitoral gland adenoma (0.2% vs. 5.8%) and mononuclear cell leukemia (0.9% vs. 16.7%) and higher incidence rates for mammary gland fibroadenoma (67.4% vs. 48.4%), mammary gland carcinoma (10.2% vs. 2.4%), and thyroid gland C cell adenoma (25.4% vs. 13.6%) relative to female F344/N rats. These represent five of the seven most common tumor types among female SD and F344/N rats in the NTP HC database. When vehicle was included as an additional matching criterion, the number of comparable F344/N rat studies dropped to four, but similar results were obtained.
C1 [Elmore, Susan A.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Elmore, Susan A.] NIEHS, Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Harris, Shawn F.] SRA Int Inc, Durham, NC USA.
[Dinse, Gregg E.; Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Elmore, SA (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
EM elmore@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU NIH, National Institute of Environmental Health Sciences [Z01ES101744,
Z01ES045007, N01ES55547]
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences
(Z01ES101744; Z01ES045007; N01ES55547). We are grateful for the
constructive comments from Michelle Hooth, Grace Kissling, and David
Malarkey.
NR 39
TC 27
Z9 29
U1 0
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD AUG
PY 2010
VL 38
IS 5
BP 765
EP 775
DI 10.1177/0192623310373777
PG 11
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 707UT
UT WOS:000286314800010
PM 20622195
ER
PT J
AU Maronpot, RR
Yoshizawa, K
Nyska, A
Harada, T
Flake, G
Mueller, G
Singh, B
Ward, JM
AF Maronpot, Robert R.
Yoshizawa, Katsuhiko
Nyska, Abraham
Harada, Takanori
Flake, Gordon
Mueller, Gundi
Singh, Bhanu
Ward, Jerrold M.
TI Hepatic Enzyme Induction: Histopathology
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE hepatocellular hypertrophy; liver toxicity; hepatocellular hyperplasia;
liver carcinogenesis; xenobiotic enzyme inducers; P450
ID DRUG-METABOLIZING-ENZYMES; ANDROGEN CYPROTERONE-ACETATE; SMOOTH
ENDOPLASMIC-RETICULUM; INDUCED LIVER ENLARGEMENT; RAT-LIVER; PEROXISOME
PROLIFERATOR; RISK-ASSESSMENT; LONG-TERM; HISTOLOGICAL CHANGE;
SPECIES-DIFFERENCES
AB Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes. The additive growth and functional demands that initiated the response to hepatic enzyme induction cover a wide range of stimuli including pregnancy and lactation, hormonal fluctuations, dietary constituents, infections associated with acute-phase proteins, as well as responses to exposure to xenobiotics. Common xenobiotic enzyme inducers trigger pathways involving the constitutive androstane receptor (CAR), the peroxisome proliferator-activated receptor (PPAR), the aryl hydrocarbon receptor (AhR), and the pregnane-X-receptor (PXR). Liver enlargement in response to hepatic enzyme induction is typically associated with hepatocellular hypertrophy and often, transient hepatocyte hyperplasia. The hypertrophy may show a lobular distribution, with the pattern of lobular zonation and severity reflecting species, strain, and sex differences in addition to effects from specific xenobiotics. Toxicity and hepatocarcinogenicity may occur when liver responses exceed adaptive changes or induced enzymes generate toxic metabolites. These undesirable consequences are influenced by the type and dose of xenobiotic and show considerable species differences in susceptibility and severity that need to be understood for assessing the potential effects on human health from similar exposures to specific xenobiotics.
C1 [Maronpot, Robert R.] Maronpot Consulting LLC, Raleigh, NC USA.
[Yoshizawa, Katsuhiko] Kansai Med Univ, Dept Pathol 2, Osaka, Japan.
[Nyska, Abraham] Tel Aviv Univ, Timrat, Israel.
[Harada, Takanori] Inst Environm Toxicol, Ibaraki, Japan.
[Flake, Gordon] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Mueller, Gundi] Merck KGaA, Darmstadt, Germany.
[Singh, Bhanu] DuPont Haskell Global Ctr Hlth & Environm Sci, Newark, DE USA.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA.
RP Maronpot, RR (reprint author), Care of Botts S, Hoffmann La Roche Inc, Toxicol & Pathol, 340 Kingsland St, Nutley, NJ 07110 USA.
NR 106
TC 45
Z9 45
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD AUG
PY 2010
VL 38
IS 5
BP 776
EP 795
DI 10.1177/0192623310373778
PG 20
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 707UT
UT WOS:000286314800011
PM 20585142
ER
PT J
AU Goodman, JI
Augustine, KA
Cunnningham, ML
Dixon, D
Dragan, YP
Falls, JG
Rasoulpour, RJ
Sills, RC
Storer, RD
Wolf, DC
Pettit, SD
AF Goodman, Jay I.
Augustine, Karen A.
Cunnningham, Michael L.
Dixon, Darlene
Dragan, Yvonne P.
Falls, James Greg
Rasoulpour, Reza J.
Sills, Robert C.
Storer, Richard D.
Wolf, Douglas C.
Pettit, Syril D.
TI What Do We Need to Know prior to Thinking about Incorporating an
Epigenetic Evaluation into Safety Assessments?(2)
SO TOXICOLOGICAL SCIENCES
LA English
DT Editorial Material
DE epigenetics; histone code; methylation; noncoding RNAs; safety
assessment
ID DNA METHYLATION; GENE-EXPRESSION; DISEASE; 5-HYDROXYMETHYLCYTOSINE;
TOXICOLOGY; EPIGENOME; PATTERNS; EXPOSURE; TARGETS; ELEGANS
AB The International Life Sciences Institute, Health and Environmental Sciences Institute sponsored a workshop entitled "State of the Science: Evaluating Epigenetic Changes," hosted by the National Institute of Environmental Health Sciences, Research Triangle Park, NC, 28-30 October 2009. The goal was to evaluate and enhance the scientific knowledge base regarding epigenetics and its role in disease, including potential relationships between epigenetic changes and transgenerational effects. A distinguishing aspect of the workshop was the highly interactive discussion session on the final morning. Meeting participants formed breakout groups (with representation from academia, industry, and government in each group) and were tasked with integrating their previous knowledge of epigenetics with what was learned during the workshop. The participants addressed the issue of what needs to be known prior to thinking about incorporating an epigenetic evaluation into safety assessment. To this end, the breakout groups were asked to address the following questions: (1) What model systems might be employed to evaluate the ability of a chemical to produce an epigenetic change (affecting the F1 and/or F3 generation); (2) What end points/targets might be evaluated; (3) What techniques might be employed; and (4) Regulatory Perspective: When is it appropriate to incorporate "new" science, in this case epigenetics, into the regulatory process? What does one need to know, what are the pitfalls and how might these be overcome/avoided? The basis of this paper is a synopsis of these discussions. The workshop highlighted the fact that the field of epigenetics is evolving at a very rapid pace and indicated that a great deal needs to be learned prior to being able to rationally incorporate an epigenetic evaluation into safety assessment. The value of the workshop is that it called attention to key data/knowledge gaps that should serve to focus attention on the areas where research and new thinking are needed to better understand epigenetics and its relationship to safety assessment.
C1 [Goodman, Jay I.] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA.
[Augustine, Karen A.] Bristol Myers Squibb Co, Discovery Toxicol, Hopewell, NJ 08543 USA.
[Cunnningham, Michael L.; Sills, Robert C.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Dragan, Yvonne P.] AstraZeneca, Wilmington, DE 19803 USA.
[Falls, James Greg] GlaxoSmithKline Inc, Safety Assessment, Res Triangle Pk, NC 27709 USA.
[Rasoulpour, Reza J.] Dow Chem Co USA, Dev & Reprod Toxicol, Midland, MI 48642 USA.
[Storer, Richard D.] Merck Res Labs, Dept Invest Lab Sci, West Point, PA 19486 USA.
[Wolf, Douglas C.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Pettit, Syril D.] Hlth & Environm Sci Inst, ILSI, Washington, DC 20005 USA.
RP Goodman, JI (reprint author), Michigan State Univ, Dept Pharmacol & Toxicol, B-440 Life Sci Bldg, E Lansing, MI 48824 USA.
EM goodman3@msu.edu
NR 23
TC 28
Z9 29
U1 1
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 AUG
PY 2010
VL 116
IS 2
BP 375
EP 381
DI 10.1093/toxsci/kfq133
PG 7
WC Toxicology
SC Toxicology
GA 630ZL
UT WOS:000280315800003
PM 20430866
ER
PT J
AU Blystone, CR
Kissling, GE
Bishop, JB
Chapin, RE
Wolfe, GW
Foster, PMD
AF Blystone, Chad R.
Kissling, Grace E.
Bishop, Jack B.
Chapin, Robert E.
Wolfe, Gary W.
Foster, Paul M. D.
TI Determination of the Di-(2-Ethylhexyl) Phthalate NOAEL for Reproductive
Development in the Rat: Importance of the Retention of Extra Animals to
Adulthood
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE phthalate; endocrine disruption; RACB; dose response; reproductive
tract; reproductive and development
ID ENDOCRINE ACTIVE AGENTS; NON-ADVERSE CHANGES; DOSE LEVELS
AB Deriving No Observed Adverse Effect Level (NOAEL) or benchmark dose is important for risk assessment and can be influenced by study design considerations. In order to define the di-(2-ethylhexyl) phthalate (DEHP) dose-response curve for reproductive malformations, we retained more offspring to adulthood to improve detection of these malformations in the reproductive assessment by continuous breeding study design. Sprague-Dawley rats were given a dietary administration of 1.5 (control), 10, 30, 100, 300, 1000, 7500, and 10,000 ppm DEHP. Male pups were evaluated for gross reproductive tract malformations (RTMs) associated with the "phthalate syndrome." DEHP treatment had minimal effects on P0 males. There was a statistically significant increase in F1 and F2 total RTMs (testis, epididymides, seminal vesicle, and prostate) in the 7500-ppm dose group and F1 10,000-ppm dose group. The 10,000-ppm exposed F1 males did not produce an F2 generation. The NOAEL for F1 and F2 RTM combined data, because in utero exposures were similar, were 100 ppm (4.8 mg/kg/day), which was close to the 5% response benchmark dose lower confidence limit of 142 ppm. The utility of evaluating more pups per litter was examined by generating power curves from a Monte Carlo simulation. These curves indicate a substantial increase in detection rate when three males are evaluated per litter rather than one. A 10% effect across male pups would be detected 5% of the time if one pup per litter was evaluated, but these effects would be detected 66% of the time if three pups per litter were evaluated. Taken together, this study provides a well-defined dose response of DEHP-induced RTMs and demonstrates that retention of more adult F1 and F2 males per litter, animals that were already produced, increases the ability to detect RTMs and presumably other low-incidence phenomena.
C1 [Blystone, Chad R.; Bishop, Jack B.; Chapin, Robert E.; Foster, Paul M. D.] Natl Inst Environm Hlth, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] Natl Inst Environm Hlth, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Wolfe, Gary W.] TherImmune Res Corp, Gaithersburg, MD 20878 USA.
RP Foster, PMD (reprint author), Natl Inst Environm Hlth, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, POB 12233 MD K2-12, Res Triangle Pk, NC 27709 USA.
EM Foster2@niehs.nih.gov
OI Chapin, Robert/0000-0002-5997-1261
FU National Institutes of Health; National Institute of Environmental
Health Sciences [1 Z01 ESO45004-11 BB]
FX Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences under Research
Project Number 1 Z01 ESO45004-11 BB.
NR 16
TC 20
Z9 23
U1 6
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2010
VL 116
IS 2
BP 640
EP 646
DI 10.1093/toxsci/kfq147
PG 7
WC Toxicology
SC Toxicology
GA 630ZL
UT WOS:000280315800026
PM 20484383
ER
PT J
AU Cho, HY
Kleeberger, SR
AF Cho, Hye-Youn
Kleeberger, Steven R.
TI Nrf2 protects against airway disorders (vol 244, pg 43, 2010)
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Correction
C1 [Cho, Hye-Youn; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
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.
NR 1
TC 1
Z9 1
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 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD AUG 1
PY 2010
VL 246
IS 3
BP 186
EP 187
DI 10.1016/j.taap.2010.03.021
PG 2
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 627MC
UT WOS:000280042700011
ER
PT J
AU Yu, MYW
Alter, HJ
Virata-Theimer, MLA
Geng, YS
Ma, L
Schechterly, CA
Colvin, CA
Luban, NLC
AF Yu, Mei-ying W.
Alter, Harvey J.
Virata-Theimer, Maria Luisa A.
Geng, Yansheng
Ma, Li
Schechterly, Cathy A.
Colvin, Camilla A.
Luban, Naomi L. C.
TI Parvovirus B19 infection transmitted by transfusion of red blood cells
confirmed by molecular analysis of linked donor and recipient samples
SO TRANSFUSION
LA English
DT Article
ID FACTOR-VIII CONCENTRATE; INTERNATIONAL STANDARD; DNA; TRANSMISSION;
PLASMA; PREVALENCE; PATIENT; IDENTIFICATION; FRACTIONATION; ORGANIZATION
AB BACKGROUND: Extremely high viremic levels of parvovirus B19 (B19V) can be found in acutely infected, but asymptomatic donors. However, reports of transmission by single-donor blood components are rare. In this prospective study, paired donor-recipient samples were used to investigate the transfusion risk.
STUDY DESIGN AND METHODS: Posttransfusion plasma or blood samples from recipients were tested for B19V DNA by polymerase chain reaction, generally at 4 and 8 weeks, and for anti-B19V immunoglobulin (Ig)G by enzyme immunoassay, at 12 and 24 weeks. To rule out infection unrelated to transfusion, pretransfusion samples and linked donor's samples for each B19V DNA positive recipient were assayed for B19V DNA and anti-B19V IgG and IgM. To confirm transmission, sequencing and phylogenetic analysis were performed.
RESULTS: A total of 14 of 869 (1.6%) recipients were B19V DNA positive, but only 1 of 869 (0.12%; 95% confidence interval, 0.0029%-0.6409%) was negative for B19V DNA and anti-B19V IgG before transfusion and seroconverted posttransfusion. This newly infected patient received 5 x 10(10) IU B19V DNA in one red blood cell (RBC) unit from an acutely infected anti-B19V negative donor in addition to RBCs from three other donors that cumulatively contained 1320 IU of anti-B19V IgG. DNA sequencing and phylogenetic analysis showed that sequences from the linked donor and recipient were identical (Genotype 1), thus establishing transfusion transmission.
CONCLUSIONS: The 0.12% transmission rate documented here, although low, could nonetheless result in hundreds or thousands of infections annually in the United States based on calculated confidence limits. Although most would be asymptomatic, some could have severe clinical outcomes, especially in neonates and those with immunocompromised or hemolytic states.
C1 [Yu, Mei-ying W.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM 345, Bethesda, MD 20892 USA.
NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Div Lab Med,Childrens Natl Med Ctr, Washington, DC 20052 USA.
RP Yu, MYW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM 345, Room 303,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM mei-ying.yu@fda.hhs.gov
FU National Institutes of Health (NIH) [R01 HL67229]; NIH Clinical Center;
CBER, FDA
FX The study was funded in part by a grant from the NIH and in part by the
Intramural Research Program of the NIH Clinical Center and that of CBER,
FDA.; The study was supported in part by a grant (R01 HL67229) from the
National Institutes of Health (NLCL and HJA). YG and LM were supported
by the Research Participation Program at the CBER administered by the
Oak Ridge Institute for Science and Education through an interagency
agreement between the US Department of Energy and the FDA. We thank Dr
J.S. Finlayson for critical review of the manuscript, Ms Hailing Yan for
performing some of the anti-B19V assays, and Dr Jessica Kim for
statistical consultation, all of them from CBER/FDA.
NR 51
TC 19
Z9 22
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD AUG
PY 2010
VL 50
IS 8
BP 1712
EP 1721
DI 10.1111/j.1537-2995.2010.02591.x
PG 10
WC Hematology
SC Hematology
GA 634PZ
UT WOS:000280596700013
PM 20158689
ER
PT J
AU Vasudevan, K
Raber, J
Sztein, J
AF Vasudevan, Kuzhalini
Raber, James
Sztein, Jorge
TI Fertility comparison between wild type and transgenic mice by in vitro
fertilization
SO TRANSGENIC RESEARCH
LA English
DT Article
DE Transgenic mice; IVF; Superovulation; Cryopreservation
ID MOUSE EMBRYOS; DEVELOPMENTAL ARREST; INSERTIONAL MUTATION;
GENETIC-CONTROL; GERM-LINE; STRAINS; GENOTYPE; INVITRO; SPERM; DNA
AB Transgenic mice are increasingly used as animal models for studies of gene function and regulation of mammalian genes. Although there has been continuous and remarkable progress in the development of transgenic technology over several decades, many aspects of the resulting transgenic model's phenotype cannot be completely predicted. For example, it is well known that as a consequence of the random insertion of the injected DNA construct, several founder mice of the new line need to be analyzed for possible differences in phenotype secondary to different insertion sites. The Knock out technique for transgenic production disrupts a specific gene by insertion or homologous recombination creating a null expression or replacement of the gene with a marker to localize it expression. This modification could result in pleiotropic phenotype if the gene is also expressed in tissues other than the target organs. Although the future breeding performance of the newly created model is critical to many studies, it is rarely anticipated that the new integrations could modify the reproductive profile of the new transgenic line. To date, few studies have demonstrated the difference between the parent strain's reproductive performance and the newly developed transgenic model. This study was designed to determine whether a genetic modification, knock out (KO) or transgenics, not anticipated to affect reproductive performance could affect the resulting reproductive profile of the newly developed transgenic mouse. More specifically, this study is designed to study the impact of the genetic modification on the ability of gametes to be fertilized in vitro. We analyzed the reproductive performance of mice with different background strains: FVB/N, C57BL/6 (129Sv/J x C57Bl/6)F1 and outbred CD1(A (R)) and compared them to mice of the same strain carrying a transgene or KO which was not anticipated to affect fertility. In vitro Fertilization was used to analyze the fertility of the mice. Oocytes from superovulated females were inseminated with sperm of same background. Fertility rate was considered as the percentage of two cell embryos scored 24 h after insemination. The data collected from this study shows that the fertilization rate is affected (reduced to half fold) in some of the transgenic mice compared to the respective Wild Type (WT) mice. For the WT the average fertility rate ranged from 80% (C57BL/6), 90% (FVB/N), 45% (129Sv/J x C57Bl/6)F1 and 43% (CD1). For transgenic mice it was 52% (C57BL/6), 65% (FVB/N), 22% (129Sv/J x C57Bl/6)F1 and 25% (CD1).
C1 [Vasudevan, Kuzhalini; Raber, James; Sztein, Jorge] NEI, Genet Engn Core Facil, NIH, Rockville, MD USA.
RP Sztein, J (reprint author), NIAID, ARTiCS, CMB, NIH, Bldg TWB 2,Room 201D,12441 Parklawn Dr, Bethesda, MD 20892 USA.
EM vasudevk@mail.nih.gov; szteinj@niaid.nih.gov
RI Sztein, Jorge/B-7165-2012;
OI Sztein, Jorge Mario/0000-0001-7047-2634
FU National Eye Institute, National Institutes of Health
FX The authors thank Christine Force for technical assistance. This study
was funded by National Eye Institute, National Institutes of Health.
NR 45
TC 11
Z9 11
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
J9 TRANSGENIC RES
JI Transgenic Res.
PD AUG
PY 2010
VL 19
IS 4
BP 587
EP 594
DI 10.1007/s11248-009-9336-2
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 624TM
UT WOS:000279844300007
PM 19844803
ER
PT J
AU Clump, DA
Yu, JJ
Cho, YJ
Gao, R
Jett, J
Zot, H
Cunnick, JM
Snyder, B
Clump, AC
Dodrill, M
Gannett, P
Coad, JE
Shurina, R
Figg, WD
Reed, E
Flynn, DC
AF Clump, David A.
Yu, Jing Jie
Cho, YoungJin
Gao, Rui
Jett, John
Zot, Henry
Cunnick, Jess M.
Snyder, Brandi
Clump, Anne C.
Dodrill, Melissa
Gannett, Peter
Coad, James E.
Shurina, Robert
Figg, W. Douglas
Reed, Eddie
Flynn, Daniel C.
TI A Polymorphic Variant of AFAP-110 Enhances cSrc Activity
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID PLECKSTRIN-HOMOLOGY DOMAIN; ACTIN-FILAMENT INTEGRITY; OVARIAN-CANCER
CELLS; INOSITOL PHOSPHATES; SIGNALING PROTEINS; TYROSINE KINASE;
ACTIVATED SRC; PH DOMAIN; PHOSPHORYLATION; ABILITY
AB Enhanced expression and activity of cSrc are associated with ovarian cancer progression. Generally, cSrc does not contain activating mutations; rather, its activity is increased in response to signals that affect a conformational change that releases its auto-inhibition. In this report, we analyzed ovarian cancer tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110 activates cSrc through a direct interaction that releases it from its autoinhibited conformation. Immunohistochemical analysis revealed a concomitant increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP-110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide polymorphism that resulted in a change of Ser403 to Cys403. In cells that express enhanced levels of cSrc, AFAP-110(403C) directed the activation of cSrc and the formation of podosomes independently of input signals, in contrast to wild-type AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data indicate a mechanism by which an inherited genetic variation could influence ovarian cancer progression and could be used to predict the response to targeted therapy.
C1 [Clump, David A.; Yu, Jing Jie; Cho, YoungJin; Cunnick, Jess M.; Snyder, Brandi; Clump, Anne C.; Dodrill, Melissa; Flynn, Daniel C.] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
[Clump, David A.; Cho, YoungJin; Clump, Anne C.; Dodrill, Melissa] W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA.
[Yu, Jing Jie; Snyder, Brandi] W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
[Gao, Rui; Figg, W. Douglas] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Jett, John; Gannett, Peter] W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA.
[Zot, Henry] Univ W Georgia, Dept Biol, Carrollton, GA USA.
[Cunnick, Jess M.; Coad, James E.] W Virginia Univ, Dept Pathol, Morgantown, WV 26506 USA.
[Shurina, Robert] Wheeling Jesuit Univ, Dept Biol, Wheeling, WV USA.
[Reed, Eddie] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, CoCHP, Atlanta, GA USA.
RP Flynn, DC (reprint author), Commonwealth Med Coll, 501 Madison Ave, Scranton, PA 18510 USA.
EM dflynn@tcmedc.org
RI Gannett, Peter/J-3347-2015; Figg Sr, William/M-2411-2016
OI Gannett, Peter/0000-0002-7859-5468;
FU National Institutes of Health [CA60731, RR16440]; Pardee Foundation;
West Virginia University
FX This work was supported by grants from the National Institutes of Health
(CA60731 and RR16440), the Pardee Foundation (D.C.F.), and the West
Virginia University Medical Scientists Training Program (D.A.C.). The
authors declare no conflict of interest.
NR 36
TC 3
Z9 5
U1 1
U2 1
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD AUG
PY 2010
VL 3
IS 4
BP 276
EP U93
DI 10.1593/tlo.10106
PG 12
WC Oncology
SC Oncology
GA 736LE
UT WOS:000288495400008
PM 20689769
ER
PT J
AU Galperin, MY
Koonin, EV
AF Galperin, Michael Y.
Koonin, Eugene V.
TI From complete genome sequence to 'complete' understanding?
SO TRENDS IN BIOTECHNOLOGY
LA English
DT Review
ID BINDING PROTEINS; YJGF/YER057C/UK114 FAMILY; FUNCTIONAL ANNOTATIONS;
CRYSTAL-STRUCTURE; TRANSFER-RNA; DATABASE; EVOLUTION; GENE; BACTERIA;
ENZYMES
AB The rapidly accumulating genome sequence data allow researchers to address fundamental biological questions that were not even asked just a few years ago. A major problem in genomics is the widening gap between the rapid progress in genome sequencing and the comparatively slow progress in the functional characterization of sequenced genomes. Here we discuss two key questions of genome biology: whether we need more genomes, and how deep is our understanding of biology based on genomic analysis. We argue that overly specific annotations of gene functions are often less useful than the more generic, but also more robust, functional assignments based on protein family classification. We also discuss problems in understanding the functions of the remaining 'conserved hypothetical' genes.
C1 [Galperin, Michael Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM galperin@ncbi.nlm.nih.gov
RI Galperin, Michael/B-5859-2013
OI Galperin, Michael/0000-0002-2265-5572
FU National Library of Medicine at the U.S. National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Library of Medicine at the U.S. National Institutes of Health.
NR 80
TC 76
Z9 78
U1 4
U2 28
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0167-7799
J9 TRENDS BIOTECHNOL
JI Trends Biotechnol.
PD AUG
PY 2010
VL 28
IS 8
BP 398
EP 406
DI 10.1016/j.tibtech.2010.05.006
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 638NY
UT WOS:000280902800002
PM 20647113
ER
PT J
AU Clemens, JQ
Calhoun, EA
Litwin, MS
Walker-Corkery, E
Markossian, T
Kusek, JW
McNaughton-Collins, M
AF Clemens, J. Quentin
Calhoun, Elizabeth A.
Litwin, Mark S.
Walker-Corkery, Elizabeth
Markossian, Talar
Kusek, John W.
McNaughton-Collins, Mary
CA Urologic Pelvic Pain Collaborative
TI A Survey of Primary Care Physician Practices in the Diagnosis and
Management of Women With Interstitial Cystitis/Painful Bladder Syndrome
SO UROLOGY
LA English
DT Article
ID SYNDROME/INTERSTITIAL CYSTITIS; PREVALENCE; POPULATION; SYMPTOMS; TIME;
PAIN; MEN
AB OBJECTIVES To describe the practice patterns among primary care physicians' (PCPs) managing patients with symptoms suggestive of interstitial cystitis/painful bladder syndrome (IC/PBS).
METHODS We developed a clinical vignette describing a woman with typical IC/PBS symptoms to elicit questions about etiology, management strategies, and familiarity with this syndrome. We mailed the questionnaire to 556 PCPs, including academicians and community physicians, in Boston, Los Angeles, and Chicago.
RESULTS We received 290 completed questionnaires (response rate, 52%). Nineteen percent of respondents reported they had "never" seen a patient like the one described in the vignette. Two-thirds of respondents correctly identified the hallmark symptom of IC/PBS (bladder pain/pressure). Regarding etiology, 90% correctly indicated that IC/PBS was a noninfectious disease, 76% correctly reported that it was not caused by a sexually transmitted infection, and 61% correctly indicated that it was not caused by a psychiatric illness. Common treatments included antibiotics and nonsteroidal anti-inflammatory agents. Referrals were often made to a specialist.
CONCLUSIONS Although most PCPs indicate familiarity with IC/PBS, they manage the condition infrequently. They also appear to have significant knowledge deficits about the clinical characteristics of IC/PBS, and they indicate variable practice patterns in the diagnosis and treatment of the condition. Educational efforts directed at PCPs will likely improve the care of patients with IC/PBS. UROLOGY 76: 323-329, 2010. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Clemens, J. Quentin] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI 48109 USA.
Univ Illinois, Sch Publ Hlth, Chicago, IL USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA.
Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Clemens, JQ (reprint author), Univ Michigan, Med Ctr, Dept Urol, 1500 Med Ctr Dr,Taubman Ctr 3875, Ann Arbor, MI 48109 USA.
EM qclemens@umich.edu
FU National Institutes of Health [U01 DK65187, DK 65277, DK 65257]
FX This research was funded by grants (U01 DK65187, DK 65277, and DK 65257)
from the National Institutes of Health.
NR 16
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD AUG
PY 2010
VL 76
IS 2
BP 323
EP 328
DI 10.1016/j.urology.2009.12.047
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 638BR
UT WOS:000280865300023
PM 20303575
ER
PT J
AU McDermott, MM
Ferrucci, L
Guralnik, JM
Dyer, AR
Liu, KA
Pearce, WH
Clark, E
Liao, YH
Criqui, MH
AF McDermott, Mary M.
Ferrucci, Luigi
Guralnik, Jack M.
Dyer, Alan R.
Liu, Kiang
Pearce, William H.
Clark, Elizabeth
Liao, Yihua
Criqui, Michael H.
TI The ankle-brachial index is associated with the magnitude of impaired
walking endurance among men and women with peripheral arterial disease
SO VASCULAR MEDICINE
LA English
DT Article
DE ankle-brachial index; intermittent claudication; peripheral arterial
disease
ID INTERMITTENT CLAUDICATION; FUNCTIONAL IMPAIRMENT; 6-MINUTE WALK;
CAPACITY; EXERCISE; TESTS
AB Previous reports suggest that the severity of peripheral arterial disease (PAD), measured by the ankle-brachial index (ABI), is not associated with the magnitude of walking impairment, measured by treadmill testing. These prior studies have had small sample sizes and included only PAD participants with symptoms of intermittent claudication. We studied the association of the ABI with diverse measures of walking performance in a cross-sectional study of 156 participants with PAD with and without intermittent claudication symptoms. Outcomes included the Gardner-Skinner treadmill test, 6-minute walk, 4-meter walking velocity at usual and fastest pace, and the walking impairment questionnaire (WIQ). Adjusting for age, sex, race, comorbidities, leg symptoms, and other confounders, lower ABI values were associated with shorter distance achieved in the 6-minute walk (ABI < 0.50: 286 meters; ABI 0.50-0.70: 316 meters; ABI 0.71-0.95: 355 meters, p trend < 0.001), shorter maximal treadmill walking time (ABI < 0.50: 6.0 minutes; ABI 0.50-0.70: 6.9 minutes; ABI 0.71-0.95: 8.3 minutes, p trend = 0.009), and lower WIQ distance scores (p trend = 0.007) among PAD participants. The ABI was not associated significantly with walking velocity over 4 meters, treadmill time to onset of leg symptoms, or the WIQ speed or stair-climbing scores. In conclusion, among 156 participants with PAD with and without intermittent claudication, lower ABI values are associated significantly with poorer walking endurance, assessed by three distinct measures. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00106327.
C1 [McDermott, Mary M.; Dyer, Alan R.; Liu, Kiang; Pearce, William H.; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi; Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA.
[Clark, Elizabeth] Mt Sinai Med Ctr, Chicago, IL USA.
[Criqui, Michael H.] Univ Calif San Diego, La Jolla, CA 92093 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung and Blood Institute [R01-HL073551]; National Center
for Research Resources, National Institutes of Health (NIH) [RR-00048];
National Institutes on Aging, NIH
FX Supported by R01-HL073551 from the National Heart, Lung and Blood
Institute and by grant #RR-00048 from the National Center for Research
Resources, National Institutes of Health (NIH). Supported in part by the
Intramural Research Program, National Institutes on Aging, NIH.
NR 29
TC 20
Z9 21
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD AUG
PY 2010
VL 15
IS 4
BP 251
EP 257
DI 10.1177/1358863X10365181
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 640VB
UT WOS:000281080700001
PM 20511294
ER
PT J
AU Waki, K
Freed, EO
AF Waki, Kayoko
Freed, Eric O.
TI Macrophages and Cell-Cell Spread of HIV-1
SO VIRUSES-BASEL
LA English
DT Review
DE HIV-1; macrophage; synapse; transmission
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; MURINE
LEUKEMIA-VIRUS; CD4(+) T-CELLS; PLASMA-MEMBRANE; VIROLOGICAL SYNAPSE;
IMMUNOLOGICAL SYNAPSE; INTRACELLULAR TRAFFICKING; DENDRITIC CELLS;
BIOLOGICAL PHENOTYPE
AB Macrophages have been postulated to play an important role in the pathogenesis of HIV-1 infection. Their ability to cross the blood-brain barrier and their resistance to virus-induced cytopathic effects allows them to serve as reservoirs for long-term infection. Thus, exploring the mechanisms of virus transmission from macrophages to target cells such as other macrophages or T lymphocytes is central to our understanding of HIV-1 pathogenesis and progression to AIDS, and is vital to the development of vaccines and novel antiretroviral therapies. This review provides an overview of the current understanding of cell-cell transmission in macrophages.
C1 [Waki, Kayoko; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM wakik@mail.nih.gov; efreed@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Intramural
AIDS Targeted Antiviral Program
FX We thank V. Piguet, Q. Sattentau, and S. Subramaniam for permission to
reproduce figures and members of Freed laboratory for helpful
discussions and critical reading of the manuscript. Research in Freed
laboratory is supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and by the
Intramural AIDS Targeted Antiviral Program.
NR 100
TC 20
Z9 21
U1 3
U2 14
PU MDPI AG
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD AUG
PY 2010
VL 2
IS 8
BP 1603
EP 1620
DI 10.3390/v2081603
PG 18
WC Virology
SC Virology
GA 658FX
UT WOS:000282477000008
PM 21552427
ER
PT J
AU Greten, TF
AF Greten, T. F.
TI First standard chemotherapy for cholangiocellular carcinoma
SO ZEITSCHRIFT FUR GASTROENTEROLOGIE
LA German
DT Editorial Material
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Greten, TF (reprint author), NCI, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0044-2771
J9 Z GASTROENTEROL
JI Z. Gastroent.
PD AUG
PY 2010
VL 48
IS 8
BP 850
EP 851
DI 10.1055/s-0029-1245417
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 635GM
UT WOS:000280643600007
PM 20687022
ER
PT J
AU Gao, XJ
O'Brien, TR
Welzel, TM
Marti, D
Qi, Y
Goedert, JJ
Phair, J
Pfeiffer, R
Carrington, M
AF Gao, Xiaojiang
O'Brien, Thomas R.
Welzel, Tania M.
Marti, Darlene
Qi, Ying
Goedert, James J.
Phair, John
Pfeiffer, Ruth
Carrington, Mary
TI HLA-B alleles associate consistently with HIV heterosexual transmission,
viral load, and progression to AIDS, but not susceptibility to infection
SO AIDS
LA English
DT Article
DE AIDS; AIDS progression; HIV; HIV transmission; human leukocyte antigen;
MHC diversity; viral load
ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSFUSION RECIPIENTS; RNA LEVELS;
PLASMA; COUPLES; RISK
AB Objective: HLA class I polymorphism is known to affect the rate of progression to AIDS after infection with HIV-1. Here we test the consistency of HLA-B allelic effects on progression to AIDS, heterosexual HIV transmission, and 'set point' viral levels.
Methods: We used adjusted Cox proportional hazard models in previously published relative hazard values for the effect of HLA-B alleles on progression to AIDS (n = 1089). The transmission study included 303 HIV-1-infected men with hemophilia and their 323 female sex partners (Multicenter Hemophilia Cohort Study cohort). Among 259 HIV-1 seroconverters (Multicenter AIDS Cohort Study cohort), HIV RNA levels at 'set point' were determined in stored plasma samples by a reverse-transcription polymerase chain reaction assay. HLA-B genotyping was performed by sequence-specific oligonucleotide hybridization and DNA sequencing.
Results: Several HLA-B alleles showed consistent associations for AIDS risk, infectivity, and 'set point' HIV RNA. HLA-B*35 was associated with more rapid progression to AIDS (relative hazard 1.39; P = 0.008), greater infectivity (odds ratio 3.14; P = 0.002), and higher HIV RNA (P = 0.01), whereas the presence of either B*27 or B*57 associated with slower progression to AIDS (B*27: relative hazard 0.49, P< 0.001; B*57: relative hazard 0.40, P< 0.0001), less infectivity (odds ratio 0.22 and 0.31, respectively, though not significant), and lower viral levels (P< 0.0001). Importantly, HLA-B polymorphism in female partners was not associated with susceptibility to HIV-1 infection.
Conclusion: HLA-B polymorphisms that affect the risk of AIDS may also alter HIV-1 infectivity, probably through the common mechanism of viral control, but they do not appear to protect against infection in our cohort. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Gao, Xiaojiang; Marti, Darlene; Qi, Ying; Carrington, Mary] SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[O'Brien, Thomas R.; Welzel, Tania M.; Goedert, James J.; Pfeiffer, Ruth] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Phair, John] Northwestern Univ, Sch Med, Chicago, IL USA.
[Gao, Xiaojiang; Marti, Darlene; Qi, Ying; Carrington, Mary] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
RP Carrington, M (reprint author), SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, POB B,Bldg 560,Room 21-89, Frederick, MD 21702 USA.
EM carringt@ncifcrf.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research; National Institute of Allergy and Infectious Diseases;
National Cancer Institute; National Heart, Lung, and Blood Institute
[UO1-AI-35042, 5-M01-RR-00052, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,
UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]
FX We would like to thank Dr Pat Martin for helpful comments regarding this
article. This project has been funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.; The MACS is
funded by the National Institute of Allergy and Infectious Diseases,
with additional supplemental funding from the National Cancer Institute;
and the National Heart, Lung, and Blood Institute: UO1-AI-35042,
5-M01-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,
UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041.
NR 23
TC 27
Z9 27
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2010
VL 24
IS 12
BP 1835
EP 1840
DI 10.1097/QAD.0b013e32833c3219
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 622WT
UT WOS:000279697400004
PM 20588164
ER
PT J
AU Mureith, MW
Chang, JJ
Lifson, JD
Ndung'u, T
Altfeld, M
AF Mureith, Marianne W.
Chang, J. Judy
Lifson, Jeffrey D.
Ndung'u, Thumbi
Altfeld, Marcus
TI Exposure to HIV-1-encoded Toll-like receptor 8 ligands enhances monocyte
response to microbial encoded Toll-like receptor 2/4 ligands
SO AIDS
LA English
DT Article; Proceedings Paper
CT 5th IAS Conference on HIV Pathogenesis
CY JUL 21, 2009
CL Cape Town, SOUTH AFRICA
SP IAS
DE HIV-1; lipopolysaccharide; microbial translocation; monocytes; Toll-like
receptors
ID ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; IMMUNE
ACTIVATION; HIV-INFECTION; SIGNALING PATHWAYS; TLR AGONISTS; CD4(+);
TRANSLOCATION; TOLERANCE; SYNERGY
AB Background: Chronic HIV-1 infection is characterized by high levels of persistent immune activation. Both HIV-1-encoded Toll-like receptor 7/8 (TLR7/8) ligands and TLR ligands encoded by products of microbial translocation have been implicated in inducing and sustaining immune activation in infected individuals, but the consequences of simultaneous exposure to different TLR ligands are not well understood.
Objective: To examine the impact of preexposure of monocytes to HIV-1-encoded TLR8 ligands on their ability to respond to subsequent stimulation with microbial TLR2/4 ligands.
Method: Stable monocytic cell lines (THP-1-Blue-CD14 cells) or primary monocytes were stimulated with ligands for TLR2, TLR4, and TLR8, including chemically inactivated HIV-1, alone, or in sequential combinations. Responses by THP-1 cells to TLR stimulation were quantified using Quanti-Blue colometric assay, and TLR-induced tumor necrosis factor-alpha production of primary monocytes was quantified by intracellular cytokine staining using flow cytometry.
Results: The exposure of monocytes to HIV-1 or HIV-1-derived TLR8 ligands sensitized these cells for TLR4 stimulation, resulting in a significantly higher response to lipopolysaccharide compared to cells that were not prestimulated with TLR8 ligands or HIV-1.
Conclusion: TLR crosstalk can enhance the pro-inflammatory monocytes response to products of microbial translocation and might play an important role in the modulation of immune function in HIV-1 infection. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Altfeld, Marcus] Harvard Univ, Sch Med, Ragon Inst MGH, MIT & Harvard, Charlestown, MA 02129 USA.
[Mureith, Marianne W.; Ndung'u, Thumbi; Altfeld, Marcus] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Med Sch, Durban, South Africa.
[Mureith, Marianne W.; Ndung'u, Thumbi; Altfeld, Marcus] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Med Sch, Durban, South Africa.
[Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Ragon Inst MGH, MIT & Harvard, 149 13th St,6th floor, Charlestown, MA 02129 USA.
EM maltfeld@partners.org
OI Ndung'u, Thumbi/0000-0003-2962-3992
FU Howard Hughes Medical Institute; NIAID NIH HHS [R21 AI071806-01A2, R21
AI071806, P01 AI074415, R21 AI071806-02, P01 AI074415-01A20001]; PHS HHS
[HHSN266200400088C]
NR 28
TC 20
Z9 24
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2010
VL 24
IS 12
BP 1841
EP 1848
DI 10.1097/QAD.0b013e32833ad89a
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 622WT
UT WOS:000279697400005
PM 20588172
ER
PT J
AU Komati, S
Shaw, PA
Stubbs, N
Mathibedi, MJ
Malan, L
Sangweni, P
Metcalf, JA
Masur, H
Hassim, S
AF Komati, Stephanus
Shaw, Pamela A.
Stubbs, Nomso
Mathibedi, Monkwe J.
Malan, Lizette
Sangweni, Phumelele
Metcalf, Julia A.
Masur, Henry
Hassim, Shaheen
TI Tuberculosis risk factors and mortality for HIV-infected persons
receiving antiretroviral therapy in South Africa
SO AIDS
LA English
DT Article
DE death; HIV/AIDS; outcome; South Africa; tuberculosis
ID COHORT; ASSOCIATION; INITIATION; ADULTS; IMPACT
AB Objective: To determine important risk factors for and impact of tuberculosis on survival in HIV-infected patients starting antiretroviral therapy (ART) in South Africa.
Design: Prospective trial of 1771 HIV-infected patients with either CD4 cell count less than 200 cells/mu l or a prior AIDS-defining illness, enrolled in randomized trial of four antiretroviral regimens.
Methods: Data collected from patient records.
Results: A history of tuberculosis at study entry was reported by 27% of patients and correlated with poor baseline health status. A history of tuberculosis at baseline was associated with subsequent tuberculosis and death during ART, but was not itself an independent risk factor for poor outcome. Tuberculosis was diagnosed during ART in 14% of patients and was more frequent during the first 3 months. Tuberculosis during therapy was independently associated with increased hazard of other AIDS-defining events and death, regardless of when during ART tuberculosis occurred. ART that consistently suppressed circulating viremia reduced but did not eliminate tuberculosis risk.
Conclusion: In HIV-infected patients who started ART at low CD4 cell counts, tuberculosis at baseline was a predictor of death, but was not independent of other factors indicating poor baseline health status. Tuberculosis during follow-up was, in contrast, an independent predictor of death even after adjustments for baseline risk factors, including CD4 cell count and viral load. Virologic failure during ART was associated with a 55% increase in risk of tuberculosis. Thus, tuberculosis is a major marker for poor outcome both at baseline and during ART and is not completely eliminated by fully suppressive ART. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Masur, Henry] NIH Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA.
[Shaw, Pamela A.; Metcalf, Julia A.; Masur, Henry] NIAID, Bethesda, MD 20892 USA.
[Komati, Stephanus; Stubbs, Nomso; Mathibedi, Monkwe J.; Malan, Lizette; Sangweni, Phumelele; Hassim, Shaheen] S African Natl Def Force, Pretoria, South Africa.
RP Masur, H (reprint author), NIH Clin Ctr, Dept Crit Care Med, NIH, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM hmasur@nih.gov
FU National Institutes of Health
FX The present study was funded by the National Institutes of Health. The
authors acknowledge the help of the South African Medical Services, the
Phidisa staff, and the study volunteers.
NR 19
TC 21
Z9 21
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2010
VL 24
IS 12
BP 1849
EP 1855
DI 10.1097/QAD.0b013e32833a2507
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 622WT
UT WOS:000279697400006
PM 20622529
ER
PT J
AU Polis, CB
Wawer, MJ
Kiwanuka, N
Laeyendecker, O
Kagaayi, J
Lutalo, T
Nalugoda, F
Kigozi, G
Serwadda, D
Gray, RH
AF Polis, Chelsea B.
Wawer, Maria J.
Kiwanuka, Noah
Laeyendecker, Oliver
Kagaayi, Joseph
Lutalo, Tom
Nalugoda, Fred
Kigozi, Godfrey
Serwadda, David
Gray, Ronald H.
TI Effect of hormonal contraceptive use on HIV progression in female HIV
seroconverters in Rakai, Uganda
SO AIDS
LA English
DT Article; Proceedings Paper
CT 17th Conference on Retroviruses and Opportunistic Infections
CY FEB 16-19, 2010
CL San Francisco, CA
DE family planning; HIV progression; hormonal contraception; survival
analysis; Uganda
ID HAZARDS REGRESSION-MODEL; DISEASE PROGRESSION; CHEMOKINE RECEPTOR;
RANDOMIZED-TRIAL; AIDS-PREVENTION; COMMUNITY TRIAL; WOMEN; MORTALITY;
PREGNANCY; RISK
AB Objective: To assess the association between hormonal contraceptive use and HIV progression.
Design: A retrospective analysis of 625 female HIV seroconverters from a Ugandan cohort study.
Methods: Multivariate Cox regression analyses incorporating time-varying hormonal contraceptive exposure were used to estimate the adjusted hazard ratios of death, and a composite outcome of AIDS or death, associated with hormonal contraceptive use. Sensitivity analyses included lagging hormonal contraceptive exposure, varying comparison groups, and separately assessing effects of oral and injectable contraceptives.
Results: A total of 27.5% of women reported ever using hormonal contraception. Of 625 women, 104 (16.6%) died and 291 (46.6%) progressed to AIDS or death during observation. Time-varying hormonal contraceptive use was not associated with an increased hazard of death as compared with nonuse of hormonal contraception (adjusted hazard ratio 0.76, 95% confidence interval 0.41-1.39, P = 0.37), and was associated with a significantly reduced hazard of progression to AIDS or death (adjusted hazard ratio 0.70, 95% confidence interval 0.50-0.97, P = 0.03). None of the sensitivity analyses suggested an adverse effect of hormonal contraception on HIV progression.
Conclusion: Hormonal contraceptive use was not associated with faster progression to death, and was associated with a reduced hazard of progression to the composite outcome of AIDS or death. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Polis, Chelsea B.; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kagaayi, Joseph; Lutalo, Tom; Nalugoda, Fred; Kigozi, Godfrey] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda.
[Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Laeyendecker, Oliver] Johns Hopkins Sch Med, Baltimore, MD USA.
[Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Polis, CB (reprint author), 615 N Wolfe St, Baltimore, MD 21205 USA.
EM cpolis@jhsph.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Polis, Chelsea/0000-0002-1031-7074; Laeyendecker,
Oliver/0000-0002-6429-4760
FU FIC NIH HHS [5D43TW00010, D43 TW000010]; Intramural NIH HHS [Z99
AI999999, ZIA AI000361-28]; NICHD NIH HHS [5P30HD06826]; PHS HHS [R01
A134265, R01 A134826]
NR 31
TC 19
Z9 19
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 JUL 31
PY 2010
VL 24
IS 12
BP 1937
EP 1944
DI 10.1097/QAD.0b013e32833b3282
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 622WT
UT WOS:000279697400016
PM 20502314
ER
PT J
AU Suzuki, S
Kulkarni, AB
AF Suzuki, Shigeki
Kulkarni, Ashok B.
TI Extracellular heat shock protein HSP90 beta secreted by MG63
osteosarcoma cells inhibits activation of latent TGF-beta 1
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Extracellular HSP90 beta; MG63 cell; Latent TGF-beta activation;
TGF-beta 1; Osteosarcoma
ID GROWTH-FACTOR-BETA; MOLECULAR-WEIGHT COMPLEX; TGF-BETA; TRANSFORMING
GROWTH-FACTOR-BETA-1; HUMAN-PLATELETS; EXPRESSION; BINDING; CANCER;
PURIFICATION; HSP90-ALPHA
AB Transforming growth factor-beta 1 (TGF-beta 1) is secreted as a latent complex, which consists of latency-associated peptide (LAP) and the mature ligand. The release of the mature ligand from LAP usually occurs through conformational change of the latent complex and is therefore considered to be the first step in the activation of the TGF-beta signaling pathway. So far, factors such as heat, pH changes, and proteolytic cleavage are reportedly involved in this activation process, but the precise molecular mechanism is still far from clear. Identification and characterization of the cell surface proteins that bind to LAP are important to our understanding of the latent TGF-beta activation process. In this study, we have identified heat shock protein 90 beta (HSP90 beta) from the cell surface of the MG63 osteosarcoma cell line as a LAP binding protein. We have also found that MG63 cells secrete HSP90 beta into extracellular space which inhibits the activation of latent TGF-beta 1, and that there is a subsequent decrease in cell proliferation. TGF-beta 1 -mediated stimulation of MG63 cells resulted in the increased cell surface expression of HSP90 beta. Thus, extracellular HSP90 beta is a negative regulator for the activation of latent TGF-beta 1 modulating TGF-beta signaling in the extracellular domain. Published by Elsevier Inc.
C1 [Suzuki, Shigeki; Kulkarni, Ashok B.] NIDCR, Funct Genom Sect, LCDB, NIH, Bethesda, MD 20892 USA.
RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Sect, LCDB, NIH, 30 Convent Dr,Room 130,MSC 4395, Bethesda, MD 20892 USA.
EM ak40m@nih.gov
FU Intramural Division of the National Institute of Dental and Craniofacial
Research, National Institutes of Health
FX We thank Drs. Kathy Flanders, Lalage Wakefield and Yoshihiko Yamada for
their critical reading of this manuscript, and Shelagh Powers for expert
editorial assistance. This work was supported by the Intramural Division
of the National Institute of Dental and Craniofacial Research, National
Institutes of Health.
NR 34
TC 20
Z9 21
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 30
PY 2010
VL 398
IS 3
BP 525
EP 531
DI 10.1016/j.bbrc.2010.06.112
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 638CB
UT WOS:000280867400033
PM 20599762
ER
PT J
AU Lopez, GY
Reitman, ZJ
Solomon, D
Waldman, T
Bigner, DD
McLendon, RE
Rosenberg, SA
Samuels, Y
Yan, H
AF Lopez, Giselle Y.
Reitman, Zachary J.
Solomon, David
Waldman, Todd
Bigner, Darell D.
McLendon, Roger E.
Rosenberg, Steven A.
Samuels, Yardena
Yan, Hai
TI IDH1(R132) mutation identified in one human melanoma metastasis, but not
correlated with metastases to the brain
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Isocitrate dehydrogenase 1; Isocitrate dehydrogenase 2; Melanoma; Brain
tumors metastases
ID IDH1; NEOPLASMS; LEUKEMIA; GLIOMAS; CANCERS
AB Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to at-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP + to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1(R132) or the homologous IDH2(R172). Melanomas share some genetic features with IDH 1/2-mutated gliomas, such as frequent TP53 mutation. We sought to test whether melanoma is associated with IDH1/2 mutations. Seventy-eight human melanoma samples were analyzed for IDH1(R132) and IDH2(R172) mutation status. A somatic, heterozygous IDH1 c.C394T (p.R132C) mutation was identified in one human melanoma metastasis to the lung. Having identified this mutation in one metastasis, we sought to test the hypothesis that certain selective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH1/2, regardless of primary tumor site. To address this, we analyzed IDH1(R132) and IDH2(R172) mutation status 53 metastatic brain tumors, including nine melanoma metastases. Results revealed no mutations in any samples. This lack of mutations would suggest that mutations in IDH1(R132) or IDH2(R172) may be necessary for the formation of tumors in a cell-lineage dependent manner, with a particularly strong selective pressure for mutations in progressive gliomas; this also suggests the lack of a particular selective pressure for growth in brain tissue in general. Studies on the cell-lineages of tumors with IDH1/2 mutations may help clarify the role of these mutations in the development of brain tumors. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lopez, Giselle Y.; Reitman, Zachary J.; Bigner, Darell D.; McLendon, Roger E.; Yan, Hai] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Pediat Brain Tumor Fdn, Durham, NC 27710 USA.
[Lopez, Giselle Y.; Reitman, Zachary J.; Bigner, Darell D.; McLendon, Roger E.; Yan, Hai] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Solomon, David; Waldman, Todd] Georgetown Univ, Sch Med, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Rosenberg, Steven A.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Yan, H (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Pediat Brain Tumor Fdn, DUMC 3156,199B MSRBI,Res Dr, Durham, NC 27710 USA.
EM giselle.lopez@duke.edu; zachary.reitman@duke.e-du; das67@georgetown.edu;
waldmant@georgetown.e-du; bigne001@mc.duke.edu; roger.mclendon@duke.edu;
samuelsy@mail.nih.gov; yan00002@mc.duke.edu
OI Lopez, Giselle/0000-0001-5435-6668
FU National Human Genome Research Institute; National Cancer Institute,
National Institutes of Health, USA; NIH [R01 CA118822]
FX We thank Kristin E. Yates for technical assistance. This work is
supported by the Intramural Research Programs of the National Human
Genome Research Institute and the National Cancer Institute, National
Institutes of Health, USA, and by NIH grant R01 CA118822.
NR 10
TC 21
Z9 21
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 30
PY 2010
VL 398
IS 3
BP 585
EP 587
DI 10.1016/j.bbrc.2010.06.125
PG 3
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 638CB
UT WOS:000280867400044
PM 20603105
ER
PT J
AU Phillips, D
Reilley, MJ
Aponte, AM
Wang, GH
Boja, E
Gucek, M
Balaban, RS
AF Phillips, Darci
Reilley, Matthew J.
Aponte, Angel M.
Wang, Guanghui
Boja, Emily
Gucek, Marjan
Balaban, Robert S.
TI Stoichiometry of STAT3 and Mitochondrial Proteins IMPLICATIONS FOR THE
REGULATION OF OXIDATIVE PHOSPHORYLATION BY PROTEIN-PROTEIN INTERACTIONS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEART; CELL; PHOSPHOPROTEOME; DYNAMICS; BIOLOGY
AB The signal transducer and activator of transcription 3 (STAT3) is a transcription factor and downstream product of cytokine and growth factor pathways. Among members of the STAT family, STAT3 has garnered particular interest due to its role in cancer and development. Recently, it was proposed that STAT3 regulates cardiac ATP generation in vivo through protein interaction with the mitochondrial complexes of oxidative phosphorylation, specifically Complexes I/II. For this mechanism to work effectively, the cellular ratio of Complexes I/II and STAT3 must approach one. However, using three different proteomic approaches in cardiac tissue, we determined the ratio of Complexes I/II and STAT3 to be similar to 10(5). This finding suggests that direct protein interaction between Complexes I/II and STAT3 cannot be required for optimal ATP production, nor can it dramatically modulate oxidative phosphorylation in vivo. Thus, STAT3 is likely altering mitochondrial function via transcriptional regulation or indirect signaling pathways that warrant further investigation.
C1 [Phillips, Darci; Reilley, Matthew J.; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Aponte, Angel M.; Wang, Guanghui; Boja, Emily; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), 9000 Rockville Pike,Bldg 10,Rm B1D 416, Bethesda, MD 20892 USA.
EM balabanr@nhlbi.nih.gov
FU National Institutes of Health Division of Intramural Research
FX This work was supported, in whole or in part, by the National Institutes
of Health Division of Intramural Research.
NR 22
TC 48
Z9 48
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 30
PY 2010
VL 285
IS 31
BP 23532
EP 23536
DI 10.1074/jbc.C110.152652
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400002
PM 20558729
ER
PT J
AU Ryan, PE
Sivadasan-Nair, N
Nau, MM
Nicholas, S
Lipkowitz, S
AF Ryan, Philip E.
Sivadasan-Nair, Nina
Nau, Marion M.
Nicholas, Sarah
Lipkowitz, Stanley
TI The N Terminus of Cbl-c Regulates Ubiquitin Ligase Activity by
Modulating Affinity for the Ubiquitin-conjugating Enzyme
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; EGF RECEPTOR; PROTEIN
UBIQUITINATION; ALLOSTERIC ACTIVATION; ANTIGEN RECEPTOR;
DOWN-REGULATION; BINDING-SITE; RING-TYPE; V-SRC
AB Cbl proteins are ubiquitin ligases (E3s) that play a significant role in regulating tyrosine kinase signaling. There are three mammalian family members: Cbl, Cbl-b, and Cbl-c. All have a highly conserved N-terminal tyrosine kinase binding domain, a catalytic RING finger domain, and a C-terminal proline-rich domain that mediates interactions with Src homology 3 (SH3) containing proteins. Although both Cbl and Cbl-b have been studied widely, little is known about Cbl-c. Published reports have demonstrated that the N terminus of Cbl and Cbl-b have an inhibitory effect on their respective E3 activity. However, the mechanism for this inhibition is still unknown. In this study we demonstrate that the N terminus of Cbl-c, like that of Cbl and Cbl-b, inhibits the E3 activity of Cbl-c. Furthermore, we map the region responsible for the inhibition to the EF-hand and SH2 domains. Phosphorylation of a critical tyrosine (Tyr-341) in the linker region of Cbl-c by Src or a phosphomimetic mutation of this tyrosine (Y341E) is sufficient to increase the E3 activity of Cbl-c. We also demonstrate for the first time that phosphorylation of Tyr-341 or the Y341E mutation leads to a decrease in affinity for the ubiquitin-conjugating enzyme (E2), UbcH5b. The decreased affinity of the Y341E mutant Cbl-c for UbcH5b results in a more rapid turnover of bound UbcH5b coincident with the increased E3 activity. These data suggest that the N terminus of Cbl-c contributes to the binding to the E2 and that phosphorylation of Tyr-341 leads to a decrease in affinity and an increase in the E3 activity of Cbl-c.
C1 [Ryan, Philip E.; Sivadasan-Nair, Nina; Nau, Marion M.; Nicholas, Sarah; Lipkowitz, Stanley] NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA.
[Ryan, Philip E.] George Washington Univ, Inst Biomed Sci, Washington, DC 20037 USA.
RP Lipkowitz, S (reprint author), NCI, LCMB, CCR, NIH, Bldg 37,Rm 2066,37 Convent Dr, Bethesda, MD 20892 USA.
EM lipkowis@mail.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 48
TC 24
Z9 29
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 JUL 30
PY 2010
VL 285
IS 31
BP 23687
EP 23698
DI 10.1074/jbc.M109.091157
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400019
PM 20525694
ER
PT J
AU Malik, M
Shukla, A
Amin, P
Niedelman, W
Lee, J
Jividen, K
Phang, JM
Ding, JH
Suh, KS
Curmi, PMG
Yuspa, SH
AF Malik, Mariam
Shukla, Anjali
Amin, Palak
Niedelman, Wendy
Lee, Jessica
Jividen, Kasey
Phang, Juanita M.
Ding, Jinhui
Suh, Kwang S.
Curmi, Paul M. G.
Yuspa, Stuart H.
TI S-Nitrosylation Regulates Nuclear Translocation of Chloride
Intracellular Channel Protein CLIC4
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; HUMAN BREAST-CANCER; ION CHANNEL; PROTEOMIC
ANALYSIS; TUMOR GRADE; IN-VITRO; EXPRESSION; APOPTOSIS; CELLS;
KERATINOCYTES
AB Nuclear translocation of chloride intracellular channel protein CLIC4 is essential for its role in Ca(2+)-induced differentiation, stress-induced apoptosis, and modulating TGF-beta signaling in mouse epidermal keratinocytes. However, post-translational modifications on CLIC4 that govern nuclear translocation and thus these activities remain to be elucidated. The structure of CLIC4 is dependent on the redox environment, in vitro, and translocation may depend on reactive oxygen and nitrogen species in the cell. Here we show that NO directly induces nuclear translocation of CLIC4 that is independent of the NO-cGMP pathway. Indeed, CLIC4 is directly modified by NO through S-nitrosylation of a cysteine residue, as measured by the biotin switch assay. NO enhances association of CLIC4 with the nuclear import proteins importin alpha and Ran. This is likely a result of the conformational change induced by S-nitrosylated CLIC4 that leads to unfolding of the protein, as exhibited by CD spectra analysis and trypsinolysis of the modified protein. Cysteine mutants of CLIC4 exhibit altered nitrosylation, nuclear residence, and stability, compared with the wild type protein likely as a consequence of altered tertiary structure. Moreover, tumor necrosis factor alpha-induced nuclear translocation of CLIC4 is dependent on nitric-oxide synthase activity. Inhibition of nitric-oxide synthase activity inhibits tumor necrosis factor alpha-induced nitrosylation and association with importin alpha and Ran and ablates CLIC4 nuclear translocation. These results suggest that S-nitrosylation governs CLIC4 structure, its association with protein partners, and thus its intracellular distribution.
C1 [Suh, Kwang S.; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Phang, Juanita M.; Curmi, Paul M. G.] Univ New S Wales, Sch Phys, Sydney, NSW 2052, Australia.
[Phang, Juanita M.; Curmi, Paul M. G.] St Vincents Hosp, Ctr Appl Med Res, Sydney, NSW 2010, Australia.
[Ding, Jinhui] NIA, Sect Bioinformat & Computat Biol, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Suh, Kwang S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Tissue Bank, Hackensack, NJ 07601 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Rm 4068A1,37 Convent Dr, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
RI Curmi, Paul/G-7185-2011; Shukla, Anjali/G-4046-2014;
OI Curmi, Paul/0000-0001-5762-7638; Jividen, Kasey/0000-0003-1022-5038;
Amin, Palak/0000-0001-5617-8703
FU National Cancer Institute; Australian Research Council; The Australian
Nuclear Science and Technology Organization
FX This work was supported, by the National Institutes of Health Intramural
Program of the National Cancer Institute and by grants from the
Australian Research Council (to P.M.G.C.). J.M.P. was supported by a
scholarship from The Australian Nuclear Science and Technology
Organization.
NR 48
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 JUL 30
PY 2010
VL 285
IS 31
BP 23818
EP 23828
DI 10.1074/jbc.M109.091611
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400032
PM 20504765
ER
PT J
AU Ishikura, S
Weissman, AM
Bonifacino, JS
AF Ishikura, Shuhei
Weissman, Allan M.
Bonifacino, Juan S.
TI Serine Residues in the Cytosolic Tail of the T-cell Antigen Receptor
alpha-Chain Mediate Ubiquitination and Endoplasmic Reticulum-associated
Degradation of the Unassembled Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ER-ASSOCIATED DEGRADATION; QUALITY-CONTROL; LIGASE; PROTEASOME; SUBUNIT;
HRD1; UBIQUITYLATION; DESTRUCTION; PROMOTES; LYSINE
AB The T-cell antigen receptor (TCR) alpha-chain (TCR alpha) is a type I integral membrane protein that becomes ubiquitinated and targeted to the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway when it fails to assemble into the heteromeric TCR complex. Remarkably, TCR alpha has a cytosolic tail of only five amino acid residues (i.e. RLWSS), none of which is the conventional ubiquitin acceptor, lysine. Herein we report that substitution of two conserved serine residues in the cytosolic tail of TCR alpha to alanine decreased ubiquitination, whereas placement of additional serine residues enhanced it. Moreover, replacement of the cytosolic serine residues by other ubiquitinatable residues (i.e. cysteine, threonine, or lysine) allowed ubiquitination to take place. Serine-dependent ubiquitination perfectly correlated with targeting of TCR alpha for ERAD. We also found that this ubiquitination was mediated by the ER-localized ubiquitin ligase, HRD1. These findings indicate that serine-dependent, HRD1-mediated ubiquitination targets TCR alpha to the ERAD pathway.
C1 [Ishikura, Shuhei; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHD, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
[Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
FU National Institutes of Health Intramural AIDS Targeted Antiviral Program
(IATAP); NICHD and NCI
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural AIDS Targeted Antiviral Program (IATAP) and the
Intramural Programs of NICHD and NCI.
NR 48
TC 39
Z9 39
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 JUL 30
PY 2010
VL 285
IS 31
BP 23916
EP 23924
DI 10.1074/jbc.M110.127936
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400042
PM 20519503
ER
PT J
AU Ranguelova, K
Chatterjee, S
Ehrenshaft, M
Ramirez, DC
Summers, FA
Kadiiska, MB
Mason, RP
AF Ranguelova, Kalina
Chatterjee, Saurabh
Ehrenshaft, Marilyn
Ramirez, Dario C.
Summers, Fiona A.
Kadiiska, Maria B.
Mason, Ronald P.
TI Protein Radical Formation Resulting from Eosinophil Peroxidase-catalyzed
Oxidation of Sulfite
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MYELOPEROXIDASE COMPOUND-I; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE;
SULFUR-DIOXIDE; MOLYBDENUM COFACTOR; THYROID PEROXIDASE; SO5-RADICALS;
OXIDASE; THIOCYANATE; ANION
AB Eosinophil peroxidase (EPO) is an abundant heme protein in eosinophils that catalyzes the formation of cytotoxic oxidants implicated in asthma, allergic inflammatory disorders, and cancer. It is known that some proteins with peroxidase activity (horseradish peroxidase and prostaglandin hydroperoxidase) can catalyze oxidation of bisulfite (hydrated sulfur dioxide), leading to the formation of sulfur trioxide anion radical ((center dot)SO(3)(-)). This free radical further reacts with oxygen to form peroxymonosulfate anion radical ((center dot)O(3)SOO(center dot)) and the very reactive sulfate anion radical (SO(4)((sic))), which is nearly as strong an oxidant as the hydroxyl radical. However, the ability of EPO to generate reactive sulfur radicals has not yet been reported. Here we demonstrate that eosinophil peroxidase/H(2)O(2) is able to oxidize bisulfite, ultimately forming the sulfate anion radical (SO(4)((sic))), and that these reactive intermediates can oxidize target proteins to protein radicals, thereby initiating protein oxidation. We used immuno-spin trapping and confocal microscopy to study protein oxidation by EPO/H(2)O(2) in the presence of bisulfite in a pure enzymatic system and in human promyelocytic leukemia HL-60 clone 15 cells, maturated to eosinophils. Polyclonal antiserum raised against the spin trap 5,5dimethyl- 1-pyrroline N-oxide (DMPO) detected the presence of DMPO covalently attached to the proteins resulting from the DMPO trapping of protein free radicals. We found that sulfite oxidation mediated by EPO/H(2)O(2) induced the formation of radical-derived DMPO spin-trapped human serum albumin and, to a lesser extent, of DMPO-EPO. These studies suggest that EPO-dependent oxidative damage may play a role in tissue injury in bisulfite-exacerbated eosinophilic inflammatory disorders.
C1 [Ranguelova, Kalina; Kadiiska, Maria B.; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Ramirez, Dario C.] Oklahoma Med Res Fdn, Free Radical Biol & Aging Res Program, Oklahoma City, OK 73104 USA.
RP Ranguelova, K (reprint author), NIEHS, Pharmacol Lab, NIH, MD F0-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM RanguelovaK@niehs.nih.gov
RI RAMIREZ, DARIO/K-3312-2013
OI RAMIREZ, DARIO/0000-0001-6725-3326
FU National Institutes of Health, NIEHS
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program, NIEHS.
NR 57
TC 21
Z9 21
U1 2
U2 11
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 JUL 30
PY 2010
VL 285
IS 31
BP 24195
EP 24205
DI 10.1074/jbc.M109.069054
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400069
PM 20501663
ER
PT J
AU Yang, JH
Shelat, NY
Bush, CA
Cisar, JO
AF Yang, Jinghua
Shelat, Nirav Y.
Bush, C. Allen
Cisar, John O.
TI Structure and Molecular Characterization of Streptococcus pneumoniae
Capsular Polysaccharide 10F by Carbohydrate Engineering in Streptococcus
oralis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COAGGREGATION RECEPTOR POLYSACCHARIDES; CELL-SURFACE POLYSACCHARIDE;
ACTINOMYCES-NAESLUNDII; WALL POLYSACCHARIDES; BIOSYNTHETIC LOCI;
C-POLYSACCHARIDE; NMR; IDENTIFICATION; RECOGNITION; ASSIGNMENT
AB Although closely related at the molecular level, the capsular polysaccharide (CPS) of serotype 10F Streptococcus pneumoniae and coaggregation receptor polysaccharide (RPS) of Streptococcus oralis C104 have distinct ecological roles. CPS prevents phagocytosis of pathogenic S. pneumoniae, whereas RPS of commensal S. oralis functions as a receptor for lectin-like adhesins on other members of the dental plaque biofilm community. Results from high resolution NMR identified the recognition region of S. oralis RPS (i.e. Galf beta 1-6GalNAc beta 1-3Gal alpha) in the hexasaccharide repeat of S. pneumoniae CPS10F. The failure of this polysaccharide to support fimbriae-mediated adhesion of Actinomyces naeslundii was explained by the position of Galf, which occurred as a branch in CPS10F rather than within the linear polysaccharide chain, as in RPS. Carbohydrate engineering of S. oralis RPS with wzy from S. pneumoniae attributed formation of the Galf branch in CPS10F to the linkage of adjacent repeating units through sub terminal GalNAc in Galf beta 1-6GalNAc beta 1-3Gal alpha rather than through terminal Galf, as in RPS. A gene (wcrD) from serotype 10A S. pneumoniae was then used to engineer a linear surface polysaccharide in S. oralis that was identical to RPS except for the presence of a beta 1-3 linkage between Galf and GalNAc beta 1-3Gal alpha. This polysaccharide also failed to support adhesion of A. naeslundii, thereby establishing the essential role of beta 1-6-linked Galf in recognition of adjacent GalNAc beta 1-3Gal alpha in wild-type RPS. These findings, which illustrate a molecular approach for relating bacterial polysaccharide structure to function, provide insight into the possible evolution of S. oralis RPS from S. pneumoniae CPS.
C1 [Yang, Jinghua; Cisar, John O.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Shelat, Nirav Y.; Bush, C. Allen] Univ Maryland, Dept Chem & Biochem, Baltimore, MD 21250 USA.
RP Cisar, JO (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 3A-301,30 Convent Dr, Bethesda, MD 20892 USA.
EM john.cisar@nih.gov
FU NIDCR, National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of the NIDCR, National Institutes of Health.
NR 31
TC 9
Z9 9
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 JUL 30
PY 2010
VL 285
IS 31
BP 24217
EP 24227
DI 10.1074/jbc.M110.123562
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 630RT
UT WOS:000280291400071
PM 20507989
ER
PT J
AU Bunting, SF
Nussenzweig, A
AF Bunting, Samuel F.
Nussenzweig, Andre
TI Dangerous Liaisons: Fanconi Anemia and Toxic Nonhomologous End Joining
in DNA Crosslink Repair
SO MOLECULAR CELL
LA English
DT Editorial Material
ID PATHWAY; GENOME
AB The proper choice of repair pathway is critical to tolerating various types of DNA damage. In a recent issue of Molecular Cell, Adamo et al. (2010), along with a second report (Pace et al., 2010), describe how the Fanconi anemia (FA) pathway is involved in preventing aberrant DNA repair. These studies suggest a potentially significant new opportunity for the treatment of FA.
C1 [Bunting, Samuel F.; Nussenzweig, Andre] Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Nussenzweig, A (reprint author), Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
NR 10
TC 13
Z9 14
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 30
PY 2010
VL 39
IS 2
BP 164
EP 166
DI 10.1016/j.molcel.2010.07.016
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 634IR
UT WOS:000280574800003
PM 20670885
ER
PT J
AU Govind, CK
Qiu, HF
Ginsburg, DS
Ruan, C
Hofmeyer, K
Hu, CH
Swaminathan, V
Workman, JL
Li, B
Hinnebusch, AG
AF Govind, Chhabi K.
Qiu, Hongfang
Ginsburg, Daniel S.
Ruan, Chun
Hofmeyer, Kimberly
Hu, Cuihua
Swaminathan, Venkatesh
Workman, Jerry L.
Li, Bing
Hinnebusch, Alan G.
TI Phosphorylated Pol II CTD Recruits Multiple HDACs, Including Rpd3C(S),
for Methylation-Dependent Deacetylation of ORF Nucleosomes
SO MOLECULAR CELL
LA English
DT Article
ID RNA-POLYMERASE-II; HISTONE DEACETYLASE; TRANSCRIPTIONAL ACTIVATION;
TERMINAL DOMAIN; CODING REGIONS; IN-VIVO; SACCHAROMYCES-CEREVISIAE;
CRYPTIC TRANSCRIPTION; GENE ACTIVITY; COMPLEX
AB Methylation of histone H3 by Set1 and Set2 is required for deacetylation of nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are cotranscriptionally recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5-phosphorylated Pol II and histones in extracts, but only the histone interactions require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation activities, their cotranscriptional recruitment is stimulated by the phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing cotranscriptional histone eviction. A strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylation is important for nucleosome eviction.
C1 [Govind, Chhabi K.; Qiu, Hongfang; Ginsburg, Daniel S.; Hofmeyer, Kimberly; Hu, Cuihua; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
[Govind, Chhabi K.] Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA.
[Ruan, Chun; Li, Bing] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
[Swaminathan, Venkatesh; Workman, Jerry L.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
RP Govind, CK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
EM govind@oakland.edu; ahinnebusch@nih.gov
OI Venkatesh, Swaminathan/0000-0001-9837-1501
FU NIH; Welch Foundation [I-1713]; American Heart Association
FX We thank Joe Reese and Steven Hahn for HDA and kin28-as mutant strains
and David Stillman for Rpd3 antibodies. This work was supported in part
by the Intramural Research Program of the NIH. B.L. is supported by the
Welch Foundation (I-1713) and the American Heart Association and is a
W.A. "Tex" Moncrief, Jr. Scholar in Medical Research.
NR 48
TC 113
Z9 115
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 30
PY 2010
VL 39
IS 2
BP 234
EP 246
DI 10.1016/j.molcel.2010.07.003
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 634IR
UT WOS:000280574800010
PM 20670892
ER
PT J
AU Onodera, T
Sakai, T
Hsu, JC
Matsumoto, K
Chiorini, JA
Yamada, KM
AF Onodera, Tomohiro
Sakai, Takayoshi
Hsu, Jeff Chi-feng
Matsumoto, Kazue
Chiorini, John A.
Yamada, Kenneth M.
TI Btbd7 Regulates Epithelial Cell Dynamics and Branching Morphogenesis
SO SCIENCE
LA English
DT Article
ID FIBRONECTIN; TUBULOGENESIS; LUNG; POLARITY; DOMAIN; ROLES
AB During embryonic development, many organs form by extensive branching of epithelia through the formation of clefts and buds. In cleft formation, buds are delineated by the conversion of epithelial cell-cell adhesions to cell-matrix adhesions, but the mechanisms of cleft formation are not clear. We have identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7 provides a mechanistic link between the extracellular matrix and cleft propagation through its highly focal expression leading to local regulation of Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments show that Btbd7 is required for branching of embryonic mammalian salivary glands and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue remodeling and formation of branched organs.
C1 [Onodera, Tomohiro; Sakai, Takayoshi; Hsu, Jeff Chi-feng; Matsumoto, Kazue; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Sakai, Takayoshi] Osaka Univ, Grad Sch Dent, Dept Oral Facial Disorders, Suita, Osaka 5650871, Japan.
[Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Sakai, T (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM sakai@dent.osaka-u.ac.jp; kyamada@mail.nih.gov
RI Onodera, Tomohiro/G-1686-2012;
OI Yamada, Kenneth/0000-0003-1512-6805
FU Japan Society for the Promotion of Science (JSPS) [21390534]; NIH, NIDCR
FX We thank M. Hoffman, M. Larsen, and K. Musselmann for advice. T.O. was
supported by a fellowship from the Japan Society for the Promotion of
Science (JSPS). This work was supported in part by the Intramural
Research Program of the NIH, NIDCR, and by Grants-in-Aid for Scientific
Research (B) (21390534) from the JSPS to T. S. The SAGE data sets are
available at the Gene Expression Omnibus (GEO) database under accession
number GSE22374.
NR 25
TC 59
Z9 62
U1 2
U2 21
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 JUL 30
PY 2010
VL 329
IS 5991
BP 562
EP 565
DI 10.1126/science.1191880
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 633EX
UT WOS:000280483500036
PM 20671187
ER
PT J
AU Nam, JM
Kwon, D
AF Nam, Jun-Mo
Kwon, Deukwoo
TI Comments on 'Non-inferiority tests for clustered matched-pair data'
Reply
SO STATISTICS IN MEDICINE
LA English
DT Letter
C1 [Nam, Jun-Mo] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Kwon, Deukwoo] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Nam, JM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JUL 30
PY 2010
VL 29
IS 17
BP 1859
EP 1860
DI 10.1002/sim.3970
PG 2
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 633WT
UT WOS:000280538400009
ER
PT J
AU Nahin, RL
Dahlhamer, JM
Stussman, BJ
AF Nahin, Richard L.
Dahlhamer, James M.
Stussman, Barbara J.
TI Health need and the use of alternative medicine among adults who do not
use conventional medicine
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID CARE UTILIZATION; UNITED-STATES; ETHNIC-DIFFERENCES; USE COMPLEMENTARY;
DISPARITIES; ACCESS; THERAPIES; PATTERNS; SERVICES; DETERMINANTS
AB Background: We hypothesize that a substantial portion of individuals who forgo conventional care in a given year turn to some form of alternative medicine. This study also examines whether individuals who use only alternative medicine will differ substantially in health and sociodemographic status from individuals using neither alternative medicine nor conventional care in a given year. To identify those factors that predict alternative medicine use in those not using conventional care, we employed the socio-behavioral model of healthcare utilization.
Methods: The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in-person from 31,044 adults throughout the 50 states and the District of Columbia.
Results: 19.3% of adults (38.3 million) did not use conventional care in a 12 month period, although 39.5% of these individuals (14.7 million) reported having one or more problems with their health. Of those not using conventional care, 24.8% (9.5 million) used alternative medicine. Users of alternative medicine had more health needs and were more likely to delay conventional care because of both cost and non-cost factors compared to those not using alternative medicine. While individual predisposing factors (gender, education) were positively associated with alternative medicine use, enabling factors (poverty status, insurance coverage) were not.
Conclusions: We found that a quarter of individuals who forgo conventional care in a given year turn towards alternative medicine. Our study suggests that the potential determinants of using only alternative medicine are multifactorial. Future research is needed to examine the decision process behind an individual's choice to use alternative medicine but not conventional medicine and the clinical outcomes of this choice.
C1 [Nahin, Richard L.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Dahlhamer, James M.; Stussman, Barbara J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Nahin, RL (reprint author), NIH, Natl Ctr Complementary & Alternat Med, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM nahinr@mail.nih.gov
OI Nahin, Richard/0000-0002-3682-4816
NR 48
TC 20
Z9 21
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JUL 29
PY 2010
VL 10
AR 220
DI 10.1186/1472-6963-10-220
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 662IU
UT WOS:000282801800001
PM 20670418
ER
PT J
AU Jang, H
Arce, FT
Ramachandran, S
Capone, R
Lal, R
Nussinov, R
AF Jang, Hyunbum
Arce, Fernando Teran
Ramachandran, Srinivasan
Capone, Ricardo
Lal, Ratnesh
Nussinov, Ruth
TI Structural Convergence Among Diverse, Toxic beta-Sheet Ion Channels
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID PROTEIN MISFOLDING DISEASES; AMYLOID PEPTIDE CHANNELS;
ALZHEIMERS-DISEASE; ZN2+-SENSITIVE CHANNEL; COMMON MECHANISM;
LIPID-BILAYERS; 3D STRUCTURE; CONGO RED; FRAGMENT; OLIGOMERS
AB Recent studies show that an array of beta-sheet peptides, including N-terminally truncated A beta peptides (A beta(11-42/17-42)), K3 (a beta(2)-microglobulin fragment), and protegrin-1 (PG-1) peptides form ion channel-like structures and elicit single channel ion conductance when reconstituted in lipid bilayers and induce cell damage through cell calcium overload. Striking similarities are observed in the dimensions of these toxic channels irrespective of their amino acid sequences. However, the intriguing question of preferred channel sizes is still unresolved. Here, exploiting ssNMR-based, U-shaped, beta-strand-turn-beta-strand coordinates, we modeled truncated A beta peptide (p3) channels with different sizes (12- to 36-mer). Molecular dynamics (MD) simulations show that optimal channel sizes of the ion channels presenting toxic ionic flux range between 16- and 24-mer. This observation is in good agreement with channel dimensions imaged by AFM for A beta(9-42), K3 fragment, and PG-1 channels and highlights the bilayer-supported preferred toxic beta-channel sizes and organization, regardless of the peptide sequence.
C1 [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
RP Lal, R (reprint author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM rlal@ucsd.edu; ruthnu@helix.nih.gov
RI Capone, Ricardo/D-1943-2010
OI Capone, Ricardo/0000-0002-7327-9837
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH (NIA); NIH National Cancer Institute, Center
for Cancer Research
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH National Cancer Institute, Center for Cancer Research. This
project has been funded by the NIH (NIA) extramural program (RL). All
simulations had been performed using the high-performance computational
facilities of the Biowulf PC/Linux cluster at the National Institutes of
Health, Bethesda, MD (http://biowulf.nih.gov).
NR 54
TC 43
Z9 43
U1 2
U2 19
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 JUL 29
PY 2010
VL 114
IS 29
BP 9445
EP 9451
DI 10.1021/jp104073k
PG 7
WC Chemistry, Physical
SC Chemistry
GA 627VJ
UT WOS:000280071400014
PM 20608696
ER
PT J
AU Schmidt, AC
AF Schmidt, Alexander C.
TI Response to Dengue Fever -- The Good, the Bad, and the Ugly?.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID INFECTION; VACCINE
C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
NR 5
TC 23
Z9 25
U1 0
U2 2
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 JUL 29
PY 2010
VL 363
IS 5
BP 484
EP 487
DI 10.1056/NEJMcibr1005904
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 632GS
UT WOS:000280411300016
PM 20818870
ER
PT J
AU Hibbard, JU
Wilkins, I
Sun, LP
Gregory, K
Haberman, S
Hoffman, M
Kominiarek, MA
Reddy, U
Bailit, J
Branch, DW
Burkman, R
Quintero, VHG
Hatjis, CG
Landy, H
Ramirez, M
VanVeldhuisen, P
Troendle, J
Zhang, J
AF Hibbard, Judith U.
Wilkins, Isabelle
Sun, Liping
Gregory, Kimberly
Haberman, Shoshana
Hoffman, Matthew
Kominiarek, Michelle A.
Reddy, Uma
Bailit, Jennifer
Branch, D. Ware
Burkman, Ronald
Quintero, Victor Hugo Gonzalez
Hatjis, Christos G.
Landy, Helain
Ramirez, Mildred
VanVeldhuisen, Paul
Troendle, James
Zhang, Jun
CA Consortium Safe Labor
TI Respiratory Morbidity in Late Preterm Births
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID NEAR-TERM INFANTS; NEONATAL-MORTALITY; CESAREAN DELIVERY; UNITED-STATES;
RATES; RISK; COMPLICATIONS; EPIDEMIOLOGY; OUTCOMES
AB Context Late preterm births (34(0)/(7)-36(6)/(7) weeks) account for an increasing proportion of prematurity-associated short-term morbidities, particularly respiratory, that require specialized care and prolonged neonatal hospital stays.
Objective To assess short-term respiratory morbidity in late preterm births compared with term births in a contemporary cohort of deliveries in the United States.
Design, Setting, and Participants Retrospective collection of electronic data from 12 institutions (19 hospitals) across the United States on 233 844 deliveries between 2002 and 2008. Charts were abstracted for all neonates with respiratory compromise admitted to a neonatal intensive care unit (NICU), and late preterm births were compared with term births in regard to resuscitation, respiratory support, and respiratory diagnoses. A multivariate logistic regression analysis compared infants at each gestational week, controlling for factors that influence respiratory outcomes.
Main Outcome Measures Respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, respiratory failure, and standard and oscillatory ventilator support.
Results Of 19 334 late preterm births, 7055 (36.5%) were admitted to a NICU and 2032 had respiratory compromise. Of 165 993 term infants, 11 980 (7.2%) were admitted to a NICU, 1874 with respiratory morbidity. The incidence of respiratory distress syndrome was 10.5% (390/3700) for infants born at 34 weeks' gestation vs 0.3% (140/41 764) at 38 weeks. Similarly, incidence of transient tachypnea of the newborn was 6.4%(n = 236) for those born at 34 weeks vs 0.4% (n = 155) at 38 weeks, pneumonia was 1.5% (n = 55) vs 0.1% (n = 62), and respiratory failure was 1.6% (n = 61) vs 0.2% (n = 63). Standard and oscillatory ventilator support had similar patterns. Odds of respiratory distress syndrome decreased with each advancing week of gestation until 38 weeks compared with 39 to 40 weeks (adjusted odds ratio [OR] at 34 weeks, 40.1; 95% confidence interval [CI], 32.0-50.3 and at 38 weeks, 1.1; 95% CI, 0.9-1.4). At 37 weeks, odds of respiratory distress syndrome were greater than at 39 to 40 weeks (adjusted OR, 3.1; 95% CI, 2.5-3.7), but the odds at 38 weeks did not differ from 39 to 40 weeks. Similar patterns were noted for transient tachypnea of the newborn (adjusted OR at 34 weeks, 14.7; 95% CI, 11.7-18.4 and at 38 weeks, 1.0; 95% CI, 0.8-1.2), pneumonia (adjusted OR at 34 weeks, 7.6; 95% CI, 5.2-11.2 and at 38 weeks, 0.9; 95% CI, 0.6-1.2), and respiratory failure (adjusted OR at 34 weeks, 10.5; 95% CI, 6.9-16.1 and at 38 weeks, 1.4; 95% CI, 1.0-1.9).
Conclusion In a contemporary cohort, late preterm birth, compared with term delivery, was associated with increased risk of respiratory distress syndrome and other respiratory morbidity. JAMA. 2010;304(4):419-425 www.jama.com
C1 [Hibbard, Judith U.] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA.
[Sun, Liping; Reddy, Uma; Troendle, James; Zhang, Jun] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Gregory, Kimberly] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Haberman, Shoshana] Maimonides Hosp, Brooklyn, NY 11219 USA.
[Hoffman, Matthew] Christiana Care Hlth Syst, Newark, DE USA.
[Kominiarek, Michelle A.] Indiana Univ Clarian Hlth, Indianapolis, IN USA.
[Reddy, Uma] NICHHD, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA.
[Bailit, Jennifer] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Branch, D. Ware] Intermt Healthcare, Salt Lake City, UT USA.
[Branch, D. Ware] Univ Utah, Salt Lake City, UT USA.
[Burkman, Ronald] Tufts Univ, Springfield, MA USA.
[Quintero, Victor Hugo Gonzalez] Univ Miami, Miami, FL USA.
[Hatjis, Christos G.] Akron City Hosp, Summa Hlth Syst, Akron, OH USA.
[Landy, Helain] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Ramirez, Mildred] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[VanVeldhuisen, Paul] EMMES Corp, Rockville, MD USA.
RP Hibbard, JU (reprint author), Univ Illinois, Dept Obstet & Gynecol, 820 S Wood St,M-C 808, Chicago, IL 60612 USA.
EM jhibbar@uic.edu
FU Eunice Shriver Kennedy National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX This study was supported by the Intramural Research Program of the
Eunice Shriver Kennedy National Institute of Child Health and Human
Development, National Institutes of Health, through contract
HHSN267200603425C.
NR 23
TC 173
Z9 176
U1 4
U2 19
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 28
PY 2010
VL 304
IS 4
BP 419
EP 425
DI 10.1001/jama.2010.1015
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 631MA
UT WOS:000280350100025
ER
PT J
AU Shemesh, N
Ozarslan, E
Adiri, T
Basser, PJ
Cohen, Y
AF Shemesh, Noam
Oezarslan, Evren
Adiri, Tal
Basser, Peter J.
Cohen, Yoram
TI Noninvasive bipolar double-pulsed-field-gradient NMR reveals signatures
for pore size and shape in polydisperse, randomly oriented,
inhomogeneous porous media
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID DIFFUSION-TENSOR MRI; SPIN-ECHO; SELF-DIFFUSION; MAGNETIC-FIELD;
EXPERIMENTAL PARAMETERS; TISSUE MICROSTRUCTURE; SIGNAL DECAY;
DIFFRACTION; SUPPRESSION; ANISOTROPY
AB Noninvasive characterization of pore size and shape in opaque porous media is a formidable challenge. NMR diffusion-diffraction patterns were found to be exceptionally useful for obtaining such morphological features, but only when pores are monodisperse and coherently placed. When locally anisotropic pores are randomly oriented, conventional diffusion NMR methods fail. Here, we present a simple, direct, and general approach to obtain both compartment size and shape even in such settings and even when pores are characterized by internal field gradients. Using controlled porous media, we show that the bipolar-double-pulsed-field-gradient (bp-d-PFG) methodology yields diffusion-diffraction patterns from which pore size can be directly obtained. Moreover, we show that pore shape, which cannot be obtained by conventional methods, can be directly inferred from the modulation of the signal in angular bp-d-PFG experiments. This new methodology significantly broadens the types of porous media that can be studied using noninvasive diffusion-diffraction NMR. (C) 2010 American Institute of Physics. [doi:10.1063/1.3454131]
C1 [Shemesh, Noam; Adiri, Tal; Cohen, Yoram] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel.
[Oezarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20814 USA.
RP Cohen, Y (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel.
EM ycohen@post.tau.ac.il
RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011;
OI Ozarslan, Evren/0000-0003-0859-1311; Shemesh, Noam/0000-0001-6681-5876
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH
FX P.J.B. and E.O. were supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. Y.C. and N.S. were partially supported by the CONNECT
consortium administered by the European Commission under Framework
Package 7.
NR 47
TC 29
Z9 29
U1 1
U2 24
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUL 28
PY 2010
VL 133
IS 4
AR 044705
DI 10.1063/1.3454131
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 637YM
UT WOS:000280854600050
PM 20687674
ER
PT J
AU Fawzi, NL
Ying, JF
Torchia, DA
Clore, GM
AF Fawzi, Nicolas L.
Ying, Jinfa
Torchia, Dennis A.
Clore, G. Marius
TI Kinetics of Amyloid beta Monomer-to-Oligomer Exchange by NMR Relaxation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ALZHEIMERS-DISEASE; EXPERIMENTAL CONSTRAINTS; CHEMICAL-EXCHANGE;
ALPHA-SYNUCLEIN; PROTEIN; FIBRILS; ENHANCEMENT; VISUALIZATION;
AGGREGATION; ASSOCIATION
AB Recent studies have implicated non-fibrillar oligomers of the amyloid beta (A beta) peptide as the primary toxic species in Alzheimer's disease. Detailed structural and kinetic characterization of these states, however, has been difficult. Here we use NMR relaxation measurements to address the kinetics of exchange between monomeric and large, polymorphic oligomeric species of A beta(1-40). (15)N and (1)H(N) R(2) data at multiple magnetic fields were recorded for several peptide concentrations subsequent to the establishment of a stable pseudo-equilibrium between monomeric and NMR-invisible soluble oligomeric species. The increase in (15)N and (1)H(N) R(2) rates as a function of protein concentration is independent of nucleus and magnetic field and shows only a small degree of variation along the peptide chain. This phenomenon is due to a lifetime broadening effect arising from the unidirectional conversion of monomer to the NMR-invisible oligomeric species ("dark" state). At a total A beta(1-40) concentration of 300 mu M, the apparent first-order rate constant for this process is similar to 3 s(-1). Fitting the McConnell equations for two dipolar-coupled spins in two-site exchange to transfer-of-saturation profiles at two radiofrequency field strengths gives an estimate for k(off) of 73 s(-1) and transiently bound monomer (1)H(N) R(2) rates of up to 42 000 s(-1) in the tightly bound central hydrophobic region and similar to 300 s(-1) in the disordered regions, such as the first nine residues. The fraction of peptide within the "dark" oligomeric state undergoing exchange with free monomer is calculated to be similar to 3%.
C1 [Fawzi, Nicolas L.; Ying, Jinfa; Torchia, Dennis A.; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008; Fawzi, Nicolas/E-2555-2013
OI Clore, G. Marius/0000-0003-3809-1027; Fawzi, Nicolas/0000-0001-5483-0577
FU NIDDK; NIH
FX We thank M. Doucleff for help with the early part of this work; A.
Szabo, A. Bax, R. Tycko, C. Bewley, D. Baber, and D. Garrett for
discussions. This work was supported by the intramural program of NIDDK
and the AIDS Targeted Antiviral Program of the NIH Director (to G.M.C.).
NR 33
TC 67
Z9 67
U1 3
U2 43
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 JUL 28
PY 2010
VL 132
IS 29
BP 9948
EP 9951
DI 10.1021/ja1048253
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 629VH
UT WOS:000280227700006
PM 20604554
ER
PT J
AU Hsu, DT
Zak, V
Mahony, L
Sleeper, LA
Atz, AM
Levine, JC
Barker, PC
Ravishankar, C
McCrindle, BW
Williams, RV
Altmann, K
Ghanayem, NS
Margossian, R
Chung, WK
Border, WL
Pearson, GD
Stylianou, MP
Mital, S
AF Hsu, Daphne T.
Zak, Victor
Mahony, Lynn
Sleeper, Lynn A.
Atz, Andrew M.
Levine, Jami C.
Barker, Piers C.
Ravishankar, Chitra
McCrindle, Brian W.
Williams, Richard V.
Altmann, Karen
Ghanayem, Nancy S.
Margossian, Renee
Chung, Wendy K.
Border, William L.
Pearson, Gail D.
Stylianou, Mario P.
Mital, Seema
CA Pediat Heart Network Investigators
TI Enalapril in Infants With Single Ventricle Results of a Multicenter
Randomized Trial
SO CIRCULATION
LA English
DT Article
DE trials; angiotensin; heart defects; congenital; heart failure;
pediatrics
ID CONGESTIVE-HEART-FAILURE; FONTAN OPERATION; SOMATIC GROWTH; RIGHT SHUNT;
CHILDREN; CAPTOPRIL; PALLIATION; SECONDARY; DISEASE
AB Background-Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown.
Methods and Results-The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg . kg(-1) . d(-1)) or placebo who were followed up until 14 months of age. The primary end point was weight-for-age z score at 14 months. The primary analysis was intention to treat. A total of 185 infants completed the study. There were 24 and 21 withdrawals or deaths in the enalapril and placebo groups, respectively (P=0.74). Weight-for-age z score was not different between the enalapril and placebo groups (mean +/- SE -0.62 +/- 0.13 versus -0.42 +/- 0.13, P=0.28). There were no significant group differences in height-for-age z score, Ross heart failure class, brain natriuretic peptide concentration, Bayley scores of infant development, or ventricular ejection fraction. The incidence of death or transplantation was 13% and did not differ between groups. Serious adverse events occurred in 88 patients in the enalapril group and 87 in the placebo group.
Conclusions-Administration of enalapril to infants with single-ventricle physiology in the first year of life did not improve somatic growth, ventricular function, or heart failure severity. The results of this randomized trial do not support the routine use of enalapril in this population.
C1 [Hsu, Daphne T.; Altmann, Karen; Mital, Seema] Columbia Univ, Div Pediat Cardiol, Med Ctr, New York, NY USA.
[Chung, Wendy K.] Columbia Univ, Med Ctr, Div Mol Genet, New York, NY USA.
[Zak, Victor; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA.
[Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Atz, Andrew M.] Med Univ S Carolina, Div Pediat Cardiol, Charlestown, MA USA.
[Levine, Jami C.; Margossian, Renee] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Barker, Piers C.] Duke Univ, Med Ctr, Div Pediat Cardiol, Durham, NC USA.
[Ravishankar, Chitra] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA.
[Williams, Richard V.] Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada.
[Williams, Richard V.] Primary Childrens Med Ctr, Div Pediat Cardiol, Salt Lake City, UT 84103 USA.
[Ghanayem, Nancy S.] Childrens Hosp Wisconsin, Div Pediat Cardiol, Milwaukee, WI 53201 USA.
[Border, William L.] Cincinnati Childrens Hosp, Div Pediat Cardiol, Cincinnati, OH USA.
[Pearson, Gail D.; Stylianou, Mario P.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Hsu, DT (reprint author), Childrens Hosp Montefiore, Div Pediat Cardiol, 3415 Bainbridge Ave, Bronx, NY 10457 USA.
EM dhsu@montefiore.org
OI Hsu, Daphne/0000-0002-2654-0430
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292,
HL068290, HL068288, HL085057]; Food and Drug Administration Office of
Orphan Products Development
FX This study was supported by U01 grants from the National Heart, Lung,
and Blood Institute of the National Institutes of Health (HL068269,
HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288,
and HL085057) and the Food and Drug Administration Office of Orphan
Products Development.
NR 28
TC 83
Z9 84
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 27
PY 2010
VL 122
IS 4
BP 333
EP U39
DI 10.1161/CIRCULATIONAHA.109.927988
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 631CN
UT WOS:000280324300004
PM 20625111
ER
PT J
AU Peacock, WF
Braunwald, E
Abraham, W
Albert, N
Burnett, J
Christenson, R
Collins, S
Diercks, D
Fonarow, G
Hollander, J
Kellerman, A
Gheorghiade, M
Kirk, D
Levy, P
Maisel, A
Massie, BM
O'Connor, C
Pang, P
Shah, M
Sopko, G
Stevenson, L
Storrow, A
Teerlink, J
AF Peacock, W. Frank
Braunwald, Eugene
Abraham, William
Albert, Nancy
Burnett, John
Christenson, Rob
Collins, Sean
Diercks, Deborah
Fonarow, Greg
Hollander, Judd
Kellerman, Art
Gheorghiade, Mihai
Kirk, Doug
Levy, Phil
Maisel, Alan
Massie, Barry M.
O'Connor, Christopher
Pang, Peter
Shah, Monica
Sopko, George
Stevenson, Lynne
Storrow, Alan
Teerlink, John
TI National Heart, Lung, and Blood Institute Working Group on Emergency
Department Management of Acute Heart Failure Research Challenges and
Opportunities
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE emergency medicine; heart failure; research
ID IN-HOSPITAL MORTALITY; NATRIURETIC PEPTIDE; PRACTICE GUIDELINES; CARDIAC
TROPONIN; RATE-VARIABILITY; ACUTE DYSPNEA; DIAGNOSIS; TRIAL;
READMISSION; ASSOCIATION
AB This paper details the substance and recommendations arising from a meeting convened by the National Heart, Lung, and Blood Institute in August 2009, to assess the challenges and opportunities of emergency department management of acute heart failure syndrome (AHFS). The assembled faculty represented a large cross section of medical professionals spanning the medical management continuum of patients presenting with acute heart failure and included heart failure cardiologists, emergency physicians, laboratory medicine specialists, nurses, and bench scientists. Their recommendations include proposals regarding the design and conduct of emergency department-based clinical trials, suggestions regarding the development of improved methods for early detection and monitoring of AHFS, and potential needs for expanding translational and applied AHFS focused research and biotechnology. We anticipate that this review will serve as a starting point for future investigations across the spectrum of funding sources. (J Am Coll Cardiol 2010;56:343-51) (c) 2010 by the American College of Cardiology Foundation
C1 [Peacock, W. Frank; Albert, Nancy] Cleveland Clin, Emergency Med Inst, Cleveland, OH 44195 USA.
[Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Burnett, John] Mayo Fdn, Rochester, MN USA.
[Abraham, William] Ohio State Univ, Columbus, OH 43210 USA.
[Christenson, Rob] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Collins, Sean] Univ Cincinnati, Cincinnati, OH USA.
[Diercks, Deborah; Kirk, Doug] Univ Calif, Davis Med Ctr, Sacramento, CA USA.
[Fonarow, Greg] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hollander, Judd] Univ Penn, Philadelphia, PA 19104 USA.
[Kellerman, Art] Emory Sch Med, Atlanta, GA USA.
[Gheorghiade, Mihai; Pang, Peter] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Levy, Phil] Wayne State Univ, Sch Med, Detroit, MI USA.
[Maisel, Alan] Univ Calif San Diego, San Diego, CA 92103 USA.
[Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Massie, Barry M.; Teerlink, John] San Francisco VA Med Ctr, San Francisco, CA USA.
[Shah, Monica; Sopko, George] NHLBI, Bethesda, MD 20892 USA.
[O'Connor, Christopher] Duke Univ, Durham, NC USA.
[Stevenson, Lynne] Harvard Univ, Sch Med, Boston, MA USA.
[Storrow, Alan] Vanderbilt Univ, Nashville, TN USA.
RP Peacock, WF (reprint author), Cleveland Clin, Emergency Med Inst, Desk E-19,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM Peacocw@ccf.org
RI Max, Mad/E-5238-2010; Teerlink, John/D-2986-2012;
OI Max, Mad/0000-0001-6966-6829; Hollander, Judd/0000-0002-1318-2785
FU National Heart, Lung, and Blood Institute
FX Vanderbilt University, Nash ville, Tennessee. The meeting that this
manuscript was derived from was completely and solely supported by the
National Heart, Lung, and Blood Institute. For full author disclosures,
please see the end of this paper. Jay Cohn, MD, served as Guest Editor
for this paper.
NR 56
TC 35
Z9 35
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 27
PY 2010
VL 56
IS 5
BP 343
EP 351
DI 10.1016/j.jacc.2010.03.051
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 628IH
UT WOS:000280109400001
PM 20650354
ER
PT J
AU Xu, Q
Park, Y
Huang, X
Hollenbeck, A
Blair, A
Schatzkin, A
Chen, H
AF Xu, Q.
Park, Y.
Huang, X.
Hollenbeck, A.
Blair, A.
Schatzkin, A.
Chen, H.
TI Physical activities and future risk of Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID URIC-ACID LEVELS; ALZHEIMER-DISEASE; ACTIVITY SCALE; PLASMA URATE;
ELDERLY PASE; LIMB-USE; EXERCISE; DIET; HEALTH; MORTALITY
AB Objective: To prospectively investigate the relationship between physical activity and Parkinson disease (PD).
Methods: We evaluated physical activity in relation to PD among 213,701 participants of the NIH-AARP Diet and Health Study cohort. Physical activities over 4 periods (ages 15-18, 19-29, and 35-39, and in the past 10 years) were noted in 1996-1997, and physician-diagnosed PD was reported on the 2004-2006 follow-up questionnaire. Only cases diagnosed after 2000 (n = 767) were included in the analyses.
Results: Higher levels of moderate to vigorous activities at ages 35-39 or in the past 10 years as reported in 1996-1997 were associated with lower PD occurrence after 2000 with significant dose-response relationships. The multivariate odds ratios (OR) between the highest vs the lowest levels were 0.62 (95% CI confidence interval [CI] 0.48-0.81, p for trend 0.005) for ages 35-39 and 0.65 (95% CI 0.51-0.83, p for trend 0.0001) for in the past 10 years. Further analyses showed that individuals with consistent and frequent participation in moderate to vigorous activities in both periods had approximately a 40% lower risk than those who were inactive in both periods. Moderate to vigorous activities at earlier ages or light activities were not associated with PD. Finally, the association between higher moderate to vigorous physical activities and lower PD risk was demonstrated in a metaanalysis of prospective studies.
Conclusions: Although we cannot exclude the possibility that less participation in physical activity is an early marker of PD, epidemiologic evidence suggests that moderate to vigorous exercise may protect against PD. Neurology (R) 2010;75:341-348
C1 [Xu, Q.; Chen, H.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Park, Y.; Schatzkin, A.] Natl Canc Inst, Nutr Epidemiol Branch, Rockville, MD USA.
[Blair, A.] Natl Canc Inst, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA.
[Hollenbeck, A.] AARP, Washington, DC USA.
RP Chen, H (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU National Institute of Environmental Health Sciences [Z01-ES-101986];
National Cancer Institute [Z01 CP010196-02]
FX Supported by the intramural research program of the NIH, the National
Institute of Environmental Health Sciences (Z01-ES-101986), and the
National Cancer Institute (Z01 CP010196-02). Dr. Xu and Dr. Park report
no disclosures. Dr. Huang has served as a consultant for Easton
Associate, Public Healthcare, Teva Pharmaceutical Industries Ltd., and
the National Institute of Environmental Health Sciences; holds patent US
6,916,823 (issued 2005): Method of treatment of dopamine-related
dysfunction (plus foreign patents) and has filed a patent regarding
Early detection of Parkinson's disease using novel motor signs; receives
research support from the NIH/NINDS (NS060722 [ PI]), the Pennsylvania
Tobacco Settlement Fund, and Huck Institute of Penn State University;
and holds stock in BioValve Technologies, Inc. Dr. Hollenbeck serves on
the Scientific Advisory Committee of the Love/Avon Army of Women and is
a full-time salaried employee of AARP. Dr. Blair is a Scientist Emeritus
at the National Cancer Institute and serves on the editorial advisory
boards of the Scandinavian Journal of Work Environment and Health, the
American Journal of Industrial Medicine, and the Journal of Agricultural
Safety and Health; and served as the Interim Director of the
Occupational Cancer Research Centre in Toronto, Canada. Dr. Schatzkin is
an employee of the NIH National Cancer Institute and serves as Principal
Investigator of the NIH-AARP Diet and Health Study. Dr. Chen receives
NIH intramural funding (Z01-ES-101986) and serves on the editorial board
of the International Journal of Molecular Epidemiology and Genetics.
NR 32
TC 82
Z9 87
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 27
PY 2010
VL 75
IS 4
BP 341
EP 348
DI 10.1212/WNL.0b013e3181ea1597
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 631KU
UT WOS:000280346400010
PM 20660864
ER
PT J
AU Laguna-Torres, VA
Gomez, J
Aguilar, PV
Ampuero, JS
Munayco, C
Ocana, V
Perez, J
Gamero, ME
Arrasco, JC
Paz, I
Chavez, E
Cruz, R
Chavez, J
Mendocilla, S
Gomez, E
Antigoni, J
Gonzalez, S
Tejada, C
Chowell, G
Kochel, TJ
AF Alberto Laguna-Torres, Victor
Gomez, Jorge
Aguilar, Patricia V.
Ampuero, Julia S.
Munayco, Cesar
Ocana, Victor
Perez, Juan
Gamero, Maria E.
Carlos Arrasco, Juan
Paz, Irmia
Chavez, Edward
Cruz, Rollin
Chavez, Jaime
Mendocilla, Silvia
Gomez, Elizabeth
Antigoni, Juana
Gonzalez, Sofia
Tejada, Cesar
Chowell, Gerardo
Kochel, Tadeusz J.
CA Peru Influenza Working Grp
TI Changes in the Viral Distribution Pattern after the Appearance of the
Novel Influenza A H1N1 (pH1N1) Virus in Influenza-Like Illness Patients
in Peru
SO PLOS ONE
LA English
DT Article
AB Background: We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009.
Methods: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR).
Results: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case.
Conclusions: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.
C1 [Alberto Laguna-Torres, Victor; Aguilar, Patricia V.; Ampuero, Julia S.; Perez, Juan; Gamero, Maria E.; Kochel, Tadeusz J.] US Naval Med Res Ctr Detachment, Dept Virol, Lima, Peru.
[Gomez, Jorge; Munayco, Cesar; Carlos Arrasco, Juan] Minist Salud, Direcc Gen Epidemiol, Lima, Peru.
[Ocana, Victor] Minist Salud, Direcc Reg Salud Piura, Piura, Peru.
[Paz, Irmia] Univ Nacl San Agustin, Arequipa, Peru.
[Chavez, Edward] Ctr Med Mil 32 Brigada Infanteri Ejercito, Trujillo, Peru.
[Cruz, Rollin] Jefatura Salud Ejercito Peru, Lima, Peru.
[Chavez, Jaime] Direcc Reg Salud Callao, Lima, Peru.
[Mendocilla, Silvia] Minist Salud, Hosp Daniel Alcides Carr Callao, Callao, Peru.
[Gomez, Elizabeth] Minist Salud, Direcc Reg Salud Puno, Puno, Peru.
[Antigoni, Juana] Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru.
[Gonzalez, Sofia] Ctr Med Naval, Callao, Peru.
[Tejada, Cesar] Minist Salud, Hosp Santa Rosa Lima, Lima, Peru.
[Chowell, Gerardo] Arizona State Univ, Math & Computat Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ USA.
[Chowell, Gerardo] NIH, Div Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Laguna-Torres, VA (reprint author), US Naval Med Res Ctr Detachment, Dept Virol, Lima, Peru.
EM alberto.laguna@med.navy.mil
RI Munayco, Cesar/G-9990-2013; Chowell, Gerardo/F-5038-2012
OI Munayco, Cesar/0000-0001-7872-8913; Chowell, Gerardo/0000-0003-2194-2251
FU Ministry of Health of Peru; United States Dpartment of Defense
[10107_09_LI]; [62787A.873.H.B000]
FX The study was funded by the Ministry of Health of Peru and the United
States Dpartment of Defense Global Emerging Infections Systems grant
number 10107_09_LI. The Naval Medical Research Center participation was
under Protocol NMRCD.2002.0019 in compliance with all applicable federal
regulations governing the protection of human subjects. This work was
supported and funded by work unit number No. 62787A.873.H.B000. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 15
TC 16
Z9 16
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 JUL 27
PY 2010
VL 5
IS 7
AR e11719
DI 10.1371/journal.pone.0011719
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 631TQ
UT WOS:000280371800002
PM 20668548
ER
PT J
AU Neubert, FX
Mars, RB
Buch, ER
Olivier, E
Rushworth, MFS
AF Neubert, Franz-Xaver
Mars, Rogier B.
Buch, Ethan R.
Olivier, Etienne
Rushworth, Matthew F. S.
TI Cortical and subcortical interactions during action reprogramming and
their related white matter pathways
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE connectivity; diffusion-weighted imaging; inhibition; transcranial
magnetic stimulation; cognitive control
ID MEDIAL FRONTAL-CORTEX; PRIMARY MOTOR CORTEX; VENTRAL PREMOTOR CORTEX;
COGNITIVE CONTROL; SUBTHALAMIC NUCLEUS; FUNCTIONAL CONNECTIVITY;
INDIVIDUAL-DIFFERENCES; RESPONSE-INHIBITION; HUMANS; AREA
AB The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control-the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they "inhibit" habitual motor responses when environmental changes mean a different response should be made. However, whether such "inhibition" can be equated with inhibitory physiological interactions has been unclear, as has the areas' relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFG's inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus.
C1 [Neubert, Franz-Xaver; Mars, Rogier B.; Buch, Ethan R.; Olivier, Etienne; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Mars, Rogier B.; Buch, Ethan R.; Rushworth, Matthew F. S.] Univ Oxford, John Radcliffe Hosp, Funct Magnet Resonance Imaging Brain Ctr, Oxford OX3 9DU, England.
[Buch, Ethan R.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Olivier, Etienne] Catholic Univ Louvain, Inst Neurosci, B-1200 Brussels, Belgium.
RP Neubert, FX (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
EM franz.xaver.neubert@gmail.com
RI Buch, Ethan/G-1981-2011
FU German National Academic Foundation; European Community; Royal Society;
Bourse d'excellence Wallonie-Bruxelles International; Medical Research
Council of the United Kingdom
FX This work was supported by the German National Academic Foundation (to
F.-X.N.), a Marie Curie Intra-European Fellowship within the Sixth
European Community Framework Programme (to R.B.M.), a Royal Society
International Incoming Short Visits grant (to E.O. and M. F. S. R.), a
Bourse d'excellence Wallonie-Bruxelles International (to E.O.), and the
Medical Research Council of the United Kingdom (to R.B.M. and M.F.S.R.).
NR 24
TC 137
Z9 138
U1 2
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 JUL 27
PY 2010
VL 107
IS 30
BP 13240
EP 13245
DI 10.1073/pnas.1000674107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634RW
UT WOS:000280602800013
PM 20622155
ER
PT J
AU Felts, RL
Narayan, K
Estes, JD
Shi, D
Trubey, CM
Fu, J
Hartnell, LM
Ruthel, GT
Schneider, DK
Nagashima, K
Bess, JW
Bavari, S
Lowekamp, BC
Bliss, D
Lifson, JD
Subramaniam, S
AF Felts, Richard L.
Narayan, Kedar
Estes, Jacob D.
Shi, Dan
Trubey, Charles M.
Fu, Jing
Hartnell, Lisa M.
Ruthel, Gordon T.
Schneider, Douglas K.
Nagashima, Kunio
Bess, Julian W., Jr.
Bavari, Sina
Lowekamp, Bradley C.
Bliss, Donald
Lifson, Jeffrey D.
Subramaniam, Sriram
TI 3D visualization of HIV transfer at the virological synapse between
dendritic cells and T cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 3D imaging; cell-cell contact; electron tomography; viral entry;
neutralizing antibodies
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOLOGICAL SYNAPSE; INFECTIOUS SYNAPSE;
TRANSMISSION; TYPE-1; SPREAD; CYTOSKELETON; MICROVILLI; MICROSCOPY;
RESISTANT
AB The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4(+) T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4(+) T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.
C1 [Felts, Richard L.; Narayan, Kedar; Shi, Dan; Fu, Jing; Hartnell, Lisa M.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Nagashima, Kunio] NCI, Electron Microscopy Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Estes, Jacob D.; Trubey, Charles M.; Schneider, Douglas K.; Bess, Julian W., Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Ruthel, Gordon T.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Lowekamp, Bradley C.; Bliss, Donald] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
RI Fu, Jing/D-8512-2012;
OI Fu, Jing/0000-0002-7752-5417
FU National Cancer Institute [HHSN261200800001E]; IATAP program; National
Institute of General Medical Sciences
FX This work was supported by funds from the intramural program of the
National Cancer Institute and the IATAP program (to S. S.) and federal
funds from the National Cancer Institute under Contract
HHSN261200800001E (to J.D.L.). R. L. F. was supported in part by a
Pharmacology Research Associate Fellowship from the National Institute
of General Medical Sciences.
NR 38
TC 93
Z9 93
U1 5
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 JUL 27
PY 2010
VL 107
IS 30
BP 13336
EP 13341
DI 10.1073/pnas.1003040107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634RW
UT WOS:000280602800029
PM 20624966
ER
PT J
AU Deng, L
Velikovsky, CA
Xu, G
Iyer, LM
Tasumi, S
Kerzic, MC
Flajnik, MF
Aravind, L
Pancer, Z
Mariuzza, RA
AF Deng, Lu
Velikovsky, C. Alejandro
Xu, Gang
Iyer, Lakshminarayan M.
Tasumi, Satoshi
Kerzic, Melissa C.
Flajnik, Martin F.
Aravind, L.
Pancer, Zeev
Mariuzza, Roy A.
TI A structural basis for antigen recognition by the T cell-like
lymphocytes of sea lamprey
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE crystal structure; T-cell receptor; variable lymphocyte receptor;
evolution; antigen binding
ID MONOCLONAL-ANTIBODIES; ALIGNMENT ALGORITHM; IMMUNE RECEPTORS; COMPLEX;
PROTEIN; DIVERSITY; EVOLUTION; DOMAIN; DIVERSIFICATION; VERTEBRATE
AB Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called "variable lymphocyte receptors" (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like gamma delta T-cell receptors (TCRs) but unlike alpha beta TCRs, can recognize antigens directly, without a requirement for processing orantigen-presenting molecules. Thus, these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and gamma delta TCRs, and the exclusive expression on the lymphocyte surface that is unique to alpha beta and gamma delta TCRs.
C1 [Xu, Gang; Tasumi, Satoshi; Pancer, Zeev] Univ Maryland, Sch Med, Inst Marine & Environm Technol, Dept Biochem & Mol Biol, Baltimore, MD 21202 USA.
[Deng, Lu; Velikovsky, C. Alejandro; Kerzic, Melissa C.; Mariuzza, Roy A.] Univ Maryland, Inst Biosci & Biotechnol Res, WM Keck Lab Struct Biol, Rockville, MD 20850 USA.
[Deng, Lu; Velikovsky, C. Alejandro; Kerzic, Melissa C.; Mariuzza, Roy A.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
[Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Flajnik, Martin F.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Pancer, Z (reprint author), Univ Maryland, Sch Med, Inst Marine & Environm Technol, Dept Biochem & Mol Biol, Baltimore, MD 21202 USA.
EM pancer@umbi.umd.edu; mariuzza@carb.nist.gov
OI Flajnik, Martin Francis/0000-0002-2792-5084
FU National Institutes of Health [AI065610, AI083892, RR006603]; National
Science Foundation [MCB-0614672]; National Library of Medicine of the
National Institutes of Health
FX We thank H. Robinson (Brookhaven National Synchrotron Light Source) for
X-ray data collection. Support for beamline X29 comes from the Offices
of Biological and Environmental Research and of Basic Energy Sciences of
the US Department of Energy and from the National Center for Research
Resources of the National Institutes of Health. This study was supported
by National Institutes of Health Grants AI065610 (to R. A. M.), AI083892
(to Z.P. and R. A. M.), and RR006603 (to M. F. F.) and by National
Science Foundation Grant MCB-0614672 (to Z.P.). L. M. I. and L. A. were
supported by the National Library of Medicine of the National Institutes
of Health.
NR 35
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U1 0
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 JUL 27
PY 2010
VL 107
IS 30
BP 13408
EP 13413
DI 10.1073/pnas.1005475107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634RW
UT WOS:000280602800041
PM 20616002
ER
PT J
AU Duplantis, BN
Osusky, M
Schmerk, CL
Ross, DR
Bosio, CM
Nano, FE
AF Duplantis, Barry N.
Osusky, Milan
Schmerk, Crystal L.
Ross, Darrell R.
Bosio, Catharine M.
Nano, Francis E.
TI Essential genes from Arctic bacteria used to construct stable,
temperature-sensitive bacterial vaccines
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE psychrophile; Colwellia; Francisella; Mycobacterium
ID FRANCISELLA-TULARENSIS; INTRACELLULAR PATHOGEN; GENOME SEQUENCE;
DNA-LIGASE; NOVICIDA; COLD; IDENTIFICATION; MYCOBACTERIA; REPLICATION;
LIBRARY
AB All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 degrees C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis.
C1 [Duplantis, Barry N.; Osusky, Milan; Schmerk, Crystal L.; Ross, Darrell R.; Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada.
[Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Nano, FE (reprint author), Univ Victoria, Dept Biochem & Microbiol, POB 3055, Victoria, BC V8W 3P6, Canada.
EM fnano@uvic.ca
RI Bosio, Catharine/D-7456-2015
FU Bill and Melinda Gates Foundation [22851]; National Institutes of
Allergy and Infectious Diseases [5R01 AI056212-02]; Natural Sciences and
Engineering Council of Canada; Canadian Institutes of Health Research
[MOP 89812]
FX We thank L. S. D. Anthony for assistance with the animal infections, and
R. Verrall (Defence Research and Development Canada, Halifax, NS,
Canada) for Arctic Ocean samples. This work was supported by Grant 22851
from the Bill and Melinda Gates Foundation Grand Challenges Program,
Grant 5R01 AI056212-02 from the National Institutes of Allergy and
Infectious Diseases, the Natural Sciences and Engineering Council of
Canada, and Grant MOP 89812 from the Canadian Institutes of Health
Research (to F.E.N.).
NR 27
TC 12
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U1 3
U2 14
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 JUL 27
PY 2010
VL 107
IS 30
BP 13456
EP 13460
DI 10.1073/pnas.1004119107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634RW
UT WOS:000280602800049
PM 20624965
ER
PT J
AU Hong, LE
Hodgkinson, CA
Yang, YH
Sampath, H
Ross, TJ
Buchholz, B
Salmeron, BJ
Srivastava, V
Thaker, GK
Goldman, D
Stein, EA
AF Hong, L. Elliot
Hodgkinson, Colin A.
Yang, Yihong
Sampath, Hemalatha
Ross, Thomas J.
Buchholz, Brittany
Salmeron, Betty Jo
Srivastava, Vibhuti
Thaker, Gunvant K.
Goldman, David
Stein, Elliot A.
TI A genetically modulated, intrinsic cingulate circuit supports human
nicotine addiction
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genetics; imaging; smoking; functional connectivity; nAChR
ID GENOME-WIDE ASSOCIATION; MESSENGER-RNA; LUNG-CANCER; HUMAN BRAIN;
ACETYLCHOLINE-RECEPTORS; FUNCTIONAL CONNECTIVITY; DOPAMINERGIC
TERMINALS; PSYCHIATRIC-DISORDERS; DRUG-ABUSE; DEPENDENCE
AB Whole-genome searches have identified nicotinic acetylcholine receptor alpha 5-alpha 3-beta 4 subunit gene variants that are associated with smoking. How genes support this addictive and high-risk behavior through their expression in the brain remains poorly understood. Here we show that a key alpha 5 gene variant Asp398Asn is associated with a dorsal anterior cingulate-ventral striatum/extended amygdala circuit, such that the "risk allele" decreases the intrinsic resting functional connectivity strength in this circuit. Importantly, this effect is observed independently in nonsmokers and smokers, although the circuit strength distinguishes smokers from nonsmokers, predicts addiction severity in smokers, and is not secondary to smoking per se, thus representing a trait-like circuitry biomarker. This same circuit is further impaired in people with mental illnesses, who have the highest rate of smoking. Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development.
C1 [Hong, L. Elliot; Sampath, Hemalatha; Buchholz, Brittany; Thaker, Gunvant K.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
[Yang, Yihong; Ross, Thomas J.; Salmeron, Betty Jo; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
[Hodgkinson, Colin A.; Srivastava, Vibhuti; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
RP Hong, LE (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
EM ehong@mprc.umaryland.edu
RI Ross, Thomas/B-7469-2008; Goldman, David/F-9772-2010; Salmeron, Betty
Jo/M-1793-2016
OI Ross, Thomas/0000-0002-7745-3572; Goldman, David/0000-0002-1724-5405;
Salmeron, Betty Jo/0000-0003-1699-9333
FU National Institutes of Health [MH70644, MH79172, MH49826, MH77852,
MH68580, M01-RR16500, N01-DA-5-9909]; National Institute on Drug Abuse
and National Institute on Alcohol Abuse and Alcoholism; Maryland
Cigarette Restitution Fund
FX This study was supported by National Institutes of Health Grants
MH70644, MH79172, MH49826, MH77852, MH68580, M01-RR16500, and
N01-DA-5-9909; the National Institute on Drug Abuse and National
Institute on Alcohol Abuse and Alcoholism Intramural Research Programs;
and the Maryland Cigarette Restitution Fund Program.
NR 56
TC 75
Z9 77
U1 1
U2 8
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 JUL 27
PY 2010
VL 107
IS 30
BP 13509
EP 13514
DI 10.1073/pnas.1004745107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634RW
UT WOS:000280602800058
PM 20643934
ER
PT J
AU Cai, HQ
Das, S
Kamimura, Y
Long, Y
Parent, CA
Devreotes, PN
AF Cai, Huaqing
Das, Satarupa
Kamimura, Yoichiro
Long, Yu
Parent, Carole A.
Devreotes, Peter N.
TI Ras-mediated activation of the TORC2-PKB pathway is critical for
chemotaxis
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ADENYLYL-CYCLASE; LEADING-EDGE; SIGNAL RELAY; DICTYOSTELIUM-DISCOIDEUM;
HUMAN NEUTROPHILS; CELL-MOVEMENT; LIVING CELLS; G-PROTEINS;
CHEMOATTRACTANT; KINASE
AB In chemotactic cells, G protein-coupled receptors activate Ras proteins, but it is unclear how Ras-associated pathways link extracellular signaling to cell migration. We show that, in Dictyostelium discoideum, activated forms of RasC prolong the time course of TORC2 (target of rapamycin [Tor] complex 2)-mediated activation of a myristoylated protein kinase B (PKB; PKBR1) and the phosphorylation of PKB substrates, independently of phosphatidylinositol-(3,4,5)-trisphosphate. Paralleling these changes, the kinetics of chemoattractant-induced adenylyl cyclase activation and actin polymerization are extended, pseudopodial activity is increased and mislocalized, and chemotaxis is impaired. The effects of activated RasC are suppressed by deletion of the TORC2 subunit PiaA. In vitro RasC(Q62L)-dependent PKB phosphorylation can be rapidly initiated by the addition of a PiaA-associated immunocomplex to membranes of TORC2-deficient cells and blocked by TOR-specific inhibitor PP242. Furthermore, TORC2 binds specifically to the activated form of RasC. These results demonstrate that RasC is an upstream regulator of TORC2 and that the TORC2-PKB signaling mediates effects of activated Ras proteins on the cytoskeleton and cell migration.
C1 [Cai, Huaqing; Kamimura, Yoichiro; Long, Yu; Devreotes, Peter N.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
[Das, Satarupa; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Devreotes, PN (reprint author), Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
EM pnd@jhmi.edu
OI Das, Satarupa/0000-0002-4217-9972
FU National Institutes of Health (NIH) [GM 28007, GM 34933]; NIH, National
Cancer Institute, Center for Cancer Research; Helen Hay Whitney
postdoctoral fellowship
FX This work was supported by National Institutes of Health (NIH) grants GM
28007 and GM 34933 to P.N. Devreotes and by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. H. Cai is a recipient of Helen Hay Whitney postdoctoral
fellowship.
NR 43
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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 JUL 26
PY 2010
VL 190
IS 2
BP 233
EP 245
DI 10.1083/jcb.201001129
PG 13
WC Cell Biology
SC Cell Biology
GA 634OR
UT WOS:000280593300009
PM 20660630
ER
PT J
AU Dauner, JG
Pan, YJ
Hildesheim, A
Harro, C
Pinto, LA
AF Dauner, Joseph G.
Pan, Yuanji
Hildesheim, Allan
Harro, Clayton
Pinto, Ligia A.
TI Characterization of the HPV-specific memory B cell and systemic antibody
responses in women receiving an unadjuvanted HPV16 L1 VLP vaccine
SO VACCINE
LA English
DT Article
DE HPV; VLP; Vaccination; Humoral response
ID VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS TYPE-16;
MONOCLONAL-ANTIBODIES; CERVICAL-CANCER; RUBELLA-VIRUS; PROPHYLACTIC
VACCINATION; COMBINATION VACCINES; AVIDITY MATURATION; CONJUGATE
VACCINE; IMMUNE-RESPONSES
AB Human papillomavirus (HPV)-specific antibodies are proposed to be the correlate of protection afforded by HPV L1 virus-like particle (VLP) vaccines Previous studies have characterized the systemic antibody response to immunization in terms of both the quantity and the ability to neutralize HPV Here, we have adapted a generalized memory B cell ELISPOT to the HPV16 system and expanded the analysis of the systemic antibody response to include an avidity measurement of HPV 1.1 VIP-specific antibodies We show the results of the memory B cell ELISPOT significantly correlated with IgG and neutralizing antibody titers, but not with the avidity measurement This is the first comprehensive study to correlate a variety of humoral aspects potentially associated with protective immunity following vaccination with a HPV16 L1 VLP vaccine. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Dauner, Joseph G.; Pan, Yuanji; Pinto, Ligia A.] NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Harro, Clayton] Johns Hopkins Univ, Ctr Immunizat Res, Baltimore, MD 21205 USA.
RP Pinto, LA (reprint author), NCI, HPV Immunol Lab, SAIC Frederick Inc, Bldg 469,Room 202, Frederick, MD 21702 USA.
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. 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 40
TC 15
Z9 15
U1 0
U2 3
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 JUL 26
PY 2010
VL 28
IS 33
BP 5407
EP 5413
DI 10.1016/j.vaccine.2010.06.018
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 639VF
UT WOS:000281002200004
PM 20591543
ER
PT J
AU Wang, YH
Azevedo, M
Saif, LJ
Gentsch, JR
Glass, RI
Jiang, BM
AF Wang, Yuhuan
Azevedo, Marli
Saif, Linda J.
Gentsch, Jon R.
Glass, Roger I.
Jiang, Baoming
TI Inactivated rotavirus vaccine induces protective immunity in gnotobiotic
piglets
SO VACCINE
LA English
DT Article
DE Inactivated rotavirus vaccine; CDC-9; Piglets
ID SECRETING CELL RESPONSES; WA HUMAN ROTAVIRUS; IMMUNIZATION INTERVALS;
SEVERE DIARRHEA; PIGS; IMMUNOGENICITY; MICE; EFFICACY; SAFETY; LIVE
AB Live oral rotavirus vaccines that are effective in middle and high Income countries have been much less immunogenic and effective among infants in resource-limited settings Several hypotheses might explain this difference, including neutralization of the vaccine by high levels of maternal antibody in serum and breast milk, severe malnutrition, and interference by other flora and viruses in the gut. We have pursued development of an alternative parenteral rotavirus vaccine with the goal of inducing comparable levels of immunogerucity and efficacy in populations throughout the world regardless of their income levels In the present study, we assessed the immunogenicity and protection of a candidate inactivated rotavirus vaccine (IRV), the human strain CDC-9 (G1P[8]) formulated with aluminum phosphate, against rotavirus infection in gnotobiotic piglets Three doses of IRV induced high titers of rotavirus-specific IgG and neutralizing activity in the sera of gnotobiotic piglets and protection against shedding of rotavirus antigen following oral challenge with a homologous virulent human strain Wa (G1P[8]) Our findings demonstrate the proof of concept for an IRV in a large animal model and provide evidence and justification for further clinical development as an alternative candidate vaccine Published by Elsevier Ltd
C1 [Wang, Yuhuan; Gentsch, Jon R.; Glass, Roger I.; Jiang, Baoming] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA.
[Azevedo, Marli; Saif, Linda J.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Wooster, OH 44691 USA.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Jiang, BM (reprint author), Natl Ctr Immunizat & Resp Dis, Gastroenteritis & Resp Viruses Lab Branch, MS G04,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
FU Cooperative Research and Development Agreement with Sanofi Pasteur,
Lyon, France
FX We thank Charles Humphrey for performing electron microscopy analysis
and Harry Greenberg for providing the monoclonal antibody 1A10. This
study was supported in part by a Cooperative Research and Development
Agreement with Sanofi Pasteur, Lyon, France.
NR 36
TC 24
Z9 29
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 26
PY 2010
VL 28
IS 33
BP 5432
EP 5436
DI 10.1016/j.vaccine.2010.06.006
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 639VF
UT WOS:000281002200008
PM 20558244
ER
PT J
AU Wang, XS
Agarwala, R
Capra, JA
Chen, ZG
Church, DM
Ciobanu, DC
Li, ZS
Lu, L
Mozhui, K
Mulligan, MK
Nelson, SF
Pollard, KS
Taylor, WL
Thomason, DB
Williams, RW
AF Wang, Xusheng
Agarwala, Richa
Capra, John A.
Chen, Zugen
Church, Deanna M.
Ciobanu, Daniel C.
Li, Zhengsheng
Lu, Lu
Mozhui, Khyobeni
Mulligan, Megan K.
Nelson, Stanley F.
Pollard, Katherine S.
Taylor, Williams L.
Thomason, Donald B.
Williams, Robert W.
TI High-throughput sequencing of the DBA/2J mouse genome
SO BMC BIOINFORMATICS
LA English
DT Meeting Abstract
CT 9th Annual UT-ORNL-KBRIN Bioinformatics Summit
CY MAR 19-21, 2010
CL Cadiz, KY
SP Univ Texas, Oak Ridge Natl Lab, Kentucky Biomed Res Infrastructure Network
C1 [Wang, Xusheng; Li, Zhengsheng; Lu, Lu; Mozhui, Khyobeni; Mulligan, Megan K.; Taylor, Williams L.; Thomason, Donald B.; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38163 USA.
[Agarwala, Richa; Church, Deanna M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Capra, John A.; Pollard, Katherine S.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA.
[Chen, Zugen; Nelson, Stanley F.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Ciobanu, Daniel C.] Univ Nebraska, Lincoln, NE 68588 USA.
EM rwilliam@nb.uthsc.edu
RI Nelson, Stanley/D-4771-2009
NR 2
TC 11
Z9 12
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 23
PY 2010
VL 11
SU 4
AR O7
DI 10.1186/1471-2105-11-S4-O7
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 645GB
UT WOS:000281439400008
ER
PT J
AU D'Souza, W
Stonik, JA
Murphy, A
Demosky, SJ
Sethi, AA
Moore, XL
Chin-Dusting, J
Remaley, AT
Sviridov, D
AF D'Souza, Wilissa
Stonik, John A.
Murphy, Andrew
Demosky, Steven J.
Sethi, Amar A.
Moore, Xiao L.
Chin-Dusting, Jaye
Remaley, Alan T.
Sviridov, Dmitri
TI Structure/Function Relationships of Apolipoprotein A-I Mimetic Peptides
Implications for Antiatherogenic Activities of High-Density Lipoprotein
SO CIRCULATION RESEARCH
LA English
DT Article
DE mimetic peptides; high-density lipoprotein; atherosclerosis
ID AMPHIPATHIC HELICAL PEPTIDES; CASSETTE TRANSPORTER A1; E-NULL MICE;
CHOLESTEROL EFFLUX; ENDOTHELIAL-CELLS; CELLULAR CHOLESTEROL;
ANTIINFLAMMATORY PROPERTIES; INFLAMMATORY RESPONSE; ANTIOXIDANT
ACTIVITY; OXIDATIVE STRESS
AB Rationale: Apolipoprotein (apoA)-I mimetic peptides are a promising type of antiatherosclerosis therapy, but how the structural features of these peptides relate to the multiple antiatherogenic functions of HDL is poorly understood.
Objective: To establish structure/function relationships of apoA-I mimetic peptides with their antiatherogenic functions.
Methods and Results: Twenty-two bihelical apoA-I mimetic peptides were investigated in vitro for the capacity and specificity of cholesterol efflux, inhibition of inflammatory response of monocytes and endothelial cells, and inhibition of low-density lipoprotein (LDL) oxidation. It was found that mean hydrophobicity, charge, size of hydrophobic face, and angle of the link between the helices are the major factors determining the efficiency and specificity of cholesterol efflux. The peptide with optimal parameters was more effective and specific toward cholesterol efflux than human apoA-I. Charge and size of hydrophobic face were also the major factors affecting antiinflammatory properties, and the presence of cysteine and histidine residues was the main factor determining antioxidant properties. There was no significant correlation between capacities of the peptides to support individual functions; each function had its own optimal set of features.
Conclusions: None of the peptides was equally effective in all the antiatherogenic functions tested, suggesting that different functions of HDL may have different mechanisms and different structural requirements. The results do suggest, however, that rationalizing the design of apoA-I mimetic peptides may improve their therapeutic value and may lead to a better understanding of mechanisms of various antiatherogenic functions of HDL. (Circ Res. 2010;107:217-227.)
C1 [D'Souza, Wilissa; Murphy, Andrew; Moore, Xiao L.; Chin-Dusting, Jaye; Sviridov, Dmitri] Baker Heart & Diabet Inst, Melbourne, Vic 8008, Australia.
[Stonik, John A.; Demosky, Steven J.; Sethi, Amar A.; Remaley, Alan T.] NHLBI, Lipoprot Sect, NIH, Bethesda, MD 20892 USA.
RP Sviridov, D (reprint author), Baker Heart & Diabet Inst, POB 6492,St Kilda Rd, Melbourne, Vic 8008, Australia.
EM aremaley1@cc.nih.gov; Dmitri.Sviridov@Bakeridi.edu.au
FU National Heart Foundation of Australia [G 07M 3165]; National Health and
Medical Research Council of Australia; NIH; Danish Agency for Science,
Technology and Innovation
FX This study was supported by a grant from the National Heart Foundation
of Australia (G 07M 3165 to D. S. and J.C.-D.) and a postgraduate award
from the National Health and Medical Research Council of Australia (to
W.D.). D.S. and J.C.-D. are Fellows of the National Health and Medical
Research Council of Australia. Research performed by A.T.R. was
supported by intramural research funds from the NIH. A.A.S. was
supported by the Danish Agency for Science, Technology and Innovation.
NR 39
TC 41
Z9 42
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD JUL 23
PY 2010
VL 107
IS 2
BP 217
EP U110
DI 10.1161/CIRCRESAHA.110.216507
PG 22
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 629LV
UT WOS:000280201200008
PM 20508181
ER
PT J
AU Kajstura, J
Urbanek, K
Perl, S
Hosoda, T
Zheng, HQ
Ogorek, B
Ferreira-Martins, J
Goichberg, P
Rondon-Clavo, C
Sanada, F
D'Amario, D
Rota, M
del Monte, F
Orlic, D
Tisdale, J
Leri, A
Anversa, P
AF Kajstura, Jan
Urbanek, Konrad
Perl, Shira
Hosoda, Toru
Zheng, Hanqiao
Ogorek, Barbara
Ferreira-Martins, Joao
Goichberg, Polina
Rondon-Clavo, Carlos
Sanada, Fumihiro
D'Amario, Domenico
Rota, Marcello
del Monte, Federica
Orlic, Donald
Tisdale, John
Leri, Annarosa
Anversa, Piero
TI Cardiomyogenesis in the Adult Human Heart
SO CIRCULATION RESEARCH
LA English
DT Article
DE myocyte regeneration; cell lifespan; DNA repair; ploidy; cell fusion
ID CARDIAC STEM-CELLS; PROGENITOR CELLS; IN-VIVO; INFARCTED MYOCARDIUM;
CARDIOMYOCYTE RENEWAL; POLYARTERITIS-NODOSA; ACTIVATION; MYOCYTES;
HYPERTROPHY; MULTIPOTENT
AB Rationale: The ability of the human heart to regenerate large quantities of myocytes remains controversial, and the extent of myocyte renewal claimed by different laboratories varies from none to nearly 20% per year.
Objective: To address this issue, we examined the percentage of myocytes, endothelial cells, and fibroblasts labeled by iododeoxyuridine in postmortem samples obtained from cancer patients who received the thymidine analog for therapeutic purposes. Additionally, the potential contribution of DNA repair, polyploidy, and cell fusion to the measurement of myocyte regeneration was determined.
Methods and Results: The fraction of myocytes labeled by iododeoxyuridine ranged from 2.5% to 46%, and similar values were found in fibroblasts and endothelial cells. An average 22%, 20%, and 13% new myocytes, fibroblasts, and endothelial cells were generated per year, suggesting that the lifespan of these cells was approximately 4.5, 5, and 8 years, respectively. The newly formed cardiac cells showed a fully differentiated adult phenotype and did not express the senescence-associated protein p16(INK4a). Moreover, measurements by confocal microscopy and flow cytometry documented that the human heart is composed predominantly of myocytes with 2n diploid DNA content and that tetraploid and octaploid nuclei constitute only a small fraction of the parenchymal cell pool. Importantly, DNA repair, ploidy formation, and cell fusion were not implicated in the assessment of myocyte regeneration.
Conclusions: Our findings indicate that the human heart has a significant growth reserve and replaces its myocyte and nonmyocyte compartment several times during the course of life. (Circ Res. 2010; 107:305-315.)
C1 [Kajstura, Jan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA.
NHLBI, NIH, Bethesda, MD 20892 USA.
Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Inst, Boston, MA 02115 USA.
RP Kajstura, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, 75 Francis St, Boston, MA 02115 USA.
EM jkajstura@partners.org; panversa@partners.org
RI Hosoda, Toru/G-1873-2010;
OI Hosoda, Toru/0000-0002-7273-0630; Ferreira-Martins,
Joao/0000-0002-5491-9421
FU National Institutes of Health
FX This work was supported by National Institutes of Health grants.
NR 49
TC 174
Z9 182
U1 1
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD JUL 23
PY 2010
VL 107
IS 2
BP 305
EP U307
DI 10.1161/CIRCRESAHA.110.223024
PG 43
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 629LV
UT WOS:000280201200017
PM 20522802
ER
PT J
AU Liu, J
Majumdar, A
Liu, JL
Thompson, LH
Seidman, MM
AF Liu, Jia
Majumdar, Alokes
Liu, Jilan
Thompson, Lawrence H.
Seidman, Michael M.
TI Sequence Conversion by Single Strand Oligonucleotide Donors via
Non-homologous End Joining in Mammalian Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HELIX-FORMING OLIGONUCLEOTIDES; FANCONI-ANEMIA FIBROBLASTS; ZINC-FINGER
NUCLEASES; BREAK REPAIR PATHWAY; HOMOLOGOUS RECOMBINATION; DNA-REPAIR;
2'-O-(2-AMINOETHYL) RESIDUES; MRE11-RAD50-NBS1 COMPLEX;
SACCHAROMYCES-CEREVISIAE; RAD51 RECOMBINATION
AB Double strand breaks (DSBs) can be repaired by homology independent nonhomologous end joining (NHEJ) pathways involving proteins such as Ku70/80, DNAPKcs, Xrcc4/Ligase 4, and the Mre11/Rad50/Nbs1 (MRN) complex. DSBs can also be repaired by homology-dependent pathways (HDR), in which the MRN and CtIP nucleases produce single strand ends that engage homologous sequences either by strand invasion or strand annealing. The entry of ends into HDR pathways underlies protocols for genomic manipulation that combine site-specific DSBs with appropriate informational donors. Most strategies utilize long duplex donors that participate by strand invasion. Work in yeast indicates that single strand oligonucleotide (SSO) donors are also active, over considerable distance, via a single strand annealing pathway. We examined the activity of SSO donors in mammalian cells at DSBs induced either by a restriction nuclease or by a targeted interstrand cross-link. SSO donors were effective immediately adjacent to the break, but activity declined sharply beyond similar to 100 nucleotides. Overexpression of the resection nuclease CtIP increased the frequency of SSO-mediated sequence modulation distal to the break site, but had no effect on the activity of an SSO donor adjacent to the break. Genetic and in vivo competition experiments showed that sequence conversion by SSOs in the immediate vicinity of the break was not by strand invasion or strand annealing pathways. Instead these donors competed for ends that would have otherwise entered NHEJ pathways.
C1 [Liu, Jia; Majumdar, Alokes; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Liu, Jilan] Mission Res Inc, Baltimore, MD 21224 USA.
[Thompson, Lawrence H.] Lawrence Livermore Natl Lab, Biosci & Biotechnol Div, Livermore, CA 94551 USA.
RP Seidman, MM (reprint author), 251 Bayview Blvd,BRC 5B133, Baltimore, MD 21224 USA.
EM seidmanm@grc.nia.nih.gov
FU National Institutes of Health; NIA; Fanconi Anemia Research Foundation
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program, NIA, and by the Fanconi Anemia
Research Foundation, through a R&D contract with MedStar Research
Institute.
NR 94
TC 13
Z9 13
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 JUL 23
PY 2010
VL 285
IS 30
BP 23196
EP 23205
DI 10.1074/jbc.M110.123844
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 626WX
UT WOS:000279999900054
PM 20489199
ER
PT J
AU Mizuno, N
Jao, CC
Langen, R
Steven, AC
AF Mizuno, Naoko
Jao, Christine C.
Langen, Ralf
Steven, Alasdair C.
TI Multiple Modes of Endophilin-mediated Conversion of Lipid Vesicles into
Coated Tubes IMPLICATIONS FOR SYNAPTIC ENDOCYTOSIS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BIN/AMPHIPHYSIN/RVS BAR DOMAIN; MEMBRANE CURVATURE; STRUCTURAL BASIS;
ELECTRON-MICROSCOPY; MICELLE TRANSITION; DYNAMIN; AMPHIPHYSIN;
MECHANISM; INVAGINATION; SYNAPTOJANIN
AB Endophilin A1 is a BAR (Bin/amphiphysin/Rvs) protein abundant in neural synapses that senses and induces membrane curvature, contributing to neck formation in presynaptic endocytic vesicles. To investigate its role in membrane remodeling, we used cryoelectron microscopy to characterize structural changes induced in lipid vesicles by exposure to endophilin. The vesicles convert rapidly to coated tubules whose morphology reflects the local concentration of endophilin. Their diameters and curvature resemble those of synaptic vesicles in situ. Three-dimensional reconstructions of quasicylindrical tubes revealed arrays of BAR dimers, flanked by densities that we equate with amphipathic helices whose folding and membrane insertion were attested by EPR. We also observed the compression of bulbous coated tubes into 70-angstrom-wide cylindrical micelles, which appear to mimic the penultimate (hemi-fission) stage of endocytosis. Our findings suggest that the adaptability of endophilin-lipid interactions underlies dynamic changes of endocytic membranes.
C1 [Mizuno, Naoko; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jao, Christine C.; Langen, Ralf] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
RP Steven, AC (reprint author), NIAMS, Struct Biol Res Lab, NIH, Bldg 50,Rm 1517, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU NIAMS; National Institutes of Health [GM063915]
FX This work was supported, in whole or in part, by the Intramural Research
Program of NIAMS, National Institutes of Health and by National
Institutes of Health Grant GM063915 (to R. L.).
NR 49
TC 29
Z9 29
U1 1
U2 11
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 JUL 23
PY 2010
VL 285
IS 30
BP 23349
EP 23356
DI 10.1074/jbc.M110.143776
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 626WX
UT WOS:000279999900068
PM 20484046
ER
PT J
AU Smith, DL
Klein, EY
McKenzie, FE
Laxminarayan, R
AF Smith, David L.
Klein, Eili Y.
McKenzie, F. Ellis
Laxminarayan, Ramanan
TI Prospective strategies to delay the evolution of anti-malarial drug
resistance: weighing the uncertainty
SO MALARIA JOURNAL
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; ANTIBIOTIC-RESISTANCE; BIOLOGICAL COST; MALARIA;
ARTEMISININ; TRANSMISSION; MUTATIONS; MALAWI; LIMITS
AB Background: The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty.
Methods: Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models.
Results: Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT) for malaria was estimated, and a policy of multiple first-line therapies (MFTs) was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases.
Conclusions: At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults.
C1 [Smith, David L.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
[Smith, David L.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
[Klein, Eili Y.; Laxminarayan, Ramanan] Resources Future Inc, Washington, DC 20036 USA.
[Klein, Eili Y.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Laxminarayan, Ramanan] Princeton Univ, Princeton Environm Inst, Princeton, NJ 08544 USA.
[McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Smith, DL (reprint author), Univ Florida, Emerging Pathogens Inst, Bartram Carr Hall,Room 614,POB 118525, Gainesville, FL 32611 USA.
EM davesmith@ufl.edu
RI Klein, Eili/C-3745-2012; Smith, David/L-8850-2013;
OI Smith, David/0000-0003-4367-3849; Klein, Eili/0000-0002-1304-5289
FU Bill & Melinda Gates Foundation [4481]
FX This research was supported by Grant #4481, "Shaping the Global Subsidy
for Anti-malarial Drugs" from the Bill & Melinda Gates Foundation to
Ramanan Laxminarayan, Resources for the Future. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript. Preliminary findings were presented at a
conference, "Anti-malarial Drug Strategies: Getting the Most from
Anti-malarial Drugs," Prestana Kruger Lodge, Kruger National Park, South
Africa, March 30-April 3, 2008. The authors gratefully acknowledge all
the participants of that conference for their feedback and suggestions.
The authors also thank Maciej Boni for his comments on earlier drafts.
NR 27
TC 20
Z9 21
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD JUL 23
PY 2010
VL 9
AR 217
DI 10.1186/1475-2875-9-217
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 657LK
UT WOS:000282414000002
PM 20653960
ER
PT J
AU Biggs, JE
Lu, VB
Stebbing, MJ
Balasubramanyan, S
Smith, PA
AF Biggs, James E.
Lu, Van B.
Stebbing, Martin J.
Balasubramanyan, Sridhar
Smith, Peter A.
TI Is BDNF sufficient for information transfer between microglia and dorsal
horn neurons during the onset of central sensitization?
SO MOLECULAR PAIN
LA English
DT Review
ID PERIPHERAL-NERVE INJURY; TUMOR-NECROSIS-FACTOR; RAT SPINAL-CORD;
SUBSTANTIA-GELATINOSA NEURONS; ROOT GANGLION-CELLS; EXCITATORY
SYNAPTIC-TRANSMISSION; ROSTRAL VENTROMEDIAL MEDULLA; CHRONIC
CONSTRICTION INJURY; LAMINA-II NEURONS; NEUROPATHIC PAIN
AB Peripheral nerve injury activates spinal microglia. This leads to enduring changes in the properties of dorsal horn neurons that initiate central sensitization and the onset of neuropathic pain. Although a variety of neuropeptides, cytokines, chemokines and neurotransmitters have been implicated at various points in this process, it is possible that much of the information transfer between activated microglia and neurons, at least in this context, may be explicable in terms of the actions of brain derived neurotrophic factor (BDNF). Microglial-derived BDNF mediates central sensitization in lamina I by attenuating inhibitory synaptic transmission. This involves an alteration in the chloride equilibrium potential as a result of down regulation of the potassium-chloride exporter, KCC2. In lamina II, BDNF duplicates many aspects of the effects of chronic constriction injury (CCI) of the sciatic nerve on excitatory transmission. It mediates an increase in synaptic drive to putative excitatory neurons whilst reducing that to inhibitory neurons. CCI produces a specific pattern of changes in excitatory synaptic transmission to tonic, delay, phasic, transient and irregular neurons. A very similar 'injury footprint' is seen following long-term exposure to BDNF. This review presents new information on the action of BDNF and CCI on lamina II neurons, including the similarity of their actions on the kinetics and distributions of subpopulations of miniature excitatory postsynaptic currents (mEPSC). These findings raise the possibility that BDNF functions as a final common path for a convergence of perturbations that culminate in the generation of neuropathic pain.
C1 [Biggs, James E.; Balasubramanyan, Sridhar; Smith, Peter A.] Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada.
[Biggs, James E.; Smith, Peter A.] Univ Alberta, Ctr Neurosci, Edmonton, AB, Canada.
[Lu, Van B.] NIAAA, Lab Mol Physiol, NIH, Rockville, MD 20852 USA.
[Stebbing, Martin J.] RMIT Univ, Sch Med Sci, Bundoora, Vic, Australia.
RP Smith, PA (reprint author), Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada.
EM peter.a.smith@ualberta.ca
OI Lu, Van/0000-0002-4880-6455
FU Canadian Institutes of Health Research (CIHR) [81089]; Alberta Heritage
Foundation for Medical Research (AHFMR)
FX We thank Aaron Lai for carrying out ELISA measurements of BDNF
concentrations in organotypic cultures and JihuanYin for art work in
Figure 1. Supported by the Canadian Institutes of Health Research (CIHR;
Funding reference # 81089). VBL received studentship awards from CIHR
and from the Alberta Heritage Foundation for Medical Research (AHFMR).
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U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD JUL 23
PY 2010
VL 6
AR 44
DI 10.1186/1744-8069-6-44
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 658JE
UT WOS:000282485500003
PM 20653959
ER
PT J
AU Vuletic, T
Babic, SD
Ivek, T
Grgicin, D
Tomic, S
Podgornik, R
AF Vuletic, T.
Babic, S. Dolanski
Ivek, T.
Grgicin, D.
Tomic, S.
Podgornik, R.
TI Structure and dynamics of hyaluronic acid semidilute solutions: A
dielectric spectroscopy study
SO PHYSICAL REVIEW E
LA English
DT Article
ID ELECTROSTATIC PERSISTENCE LENGTH; BROAD FREQUENCY-RANGE; FLEXIBLE
POLYELECTROLYTES; BIOLOGICAL-SYSTEMS; RELAXATION; SUSPENSIONS;
DISPERSION; PARTICLES; BEHAVIOR; DILUTE
AB Dielectric spectroscopy is used to investigate fundamental length scales describing the structure of hyaluronic acid sodium salt (Na-HA) semidilute aqueous solutions. In salt-free regime, the length scale of the relaxation mode detected in MHz range scales with HA concentration as c(HA)(-0.5) and corresponds to the de Gennes-Pfeuty-Dobrynin correlation length of polyelectrolytes in semidilute solution. The same scaling was observed for the case of long, genomic DNA. Conversely, the length scale of the mode detected in kilohertz range also varies with HA concentration as c(HA)(-0.5) which differs from the case of DNA (c(DNA)(-0.25)). The observed behavior suggests that the relaxation in the kilohertz range reveals the de Gennes-Dobrynin renormalized Debye screening length, and not the average size of the chain, as the pertinent length scale. Similarly, with increasing added salt the electrostatic contribution to the HA persistence length is observed to scale as the Debye length, contrary to scaling pertinent to the Odijk-Skolnick-Fixman electrostatic persistence length observed in the case of DNA. We argue that the observed features of the kilohertz range relaxation are due to much weaker electrostatic interactions that lead to the absence of Manning condensation as well as a rather high flexibility of HA as compared to DNA.
C1 [Vuletic, T.; Babic, S. Dolanski; Ivek, T.; Grgicin, D.; Tomic, S.] Inst Za Fiziku, Zagreb, Croatia.
[Podgornik, R.] Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 61000, Slovenia.
[Podgornik, R.] Univ Ljubljana, Inst Biophys, Sch Med, Ljubljana 61000, Slovenia.
[Podgornik, R.] J Stefan Inst, Ljubljana, Slovenia.
[Podgornik, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, NIH, Bethesda, MD USA.
RP Vuletic, T (reprint author), Inst Za Fiziku, Zagreb, Croatia.
EM tvuletic@ifs.hr
RI Ivek, Tomislav/D-5298-2011; Tomic, Silvia/D-5466-2011; Podgornik,
Rudolf/C-6209-2008
OI Podgornik, Rudolf/0000-0002-3855-4637
FU Croatian Ministry of Science, Education and Sports [035-0000000-2836];
Slovenian Research Agency [P1-0055, J1-0908]; NIH, Eunice Kennedy
Shriver National Institute of Child Health and Human Development
FX We would like to thank P. A. Pincus for a valuable and illuminating
discussion. This work was supported by the Croatian Ministry of Science,
Education and Sports under Grant No. 035-0000000-2836 (Strongly
correlated inorganic, organic and biomaterials). R.P. would like to
acknowledge the financial support by the Slovenian Research Agency under
Contracts No. P1-0055 (Biophysics of Polymers, Membranes, Gels, Colloids
and Cells) and No. J1-0908 (Active media nanoactuators with dispersion
forces). This study was in part supported by the Intramural Research
Program of the NIH, Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 37
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U2 14
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD JUL 23
PY 2010
VL 82
IS 1
AR 011922
DI 10.1103/PhysRevE.82.011922
PN 1
PG 10
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 629XE
UT WOS:000280233300006
PM 20866663
ER
PT J
AU Jovanovic, K
Pastor, AM
O'Donovan, MJ
AF Jovanovic, Ksenija
Pastor, Angel M.
O'Donovan, Michael J.
TI The Use of PRV-Bartha to Define Premotor Inputs to Lumbar Motoneurons in
the Neonatal Spinal Cord of the Mouse
SO PLOS ONE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; RETROGRADE TRANSSYNAPTIC TRANSPORT; PSEUDORABIES
VIRUS; RENSHAW CELLS; MOTOR-NEURONS; COMMISSURAL INTERNEURONS;
SUPRACHIASMATIC NUCLEUS; FLUORESCENT PROTEIN; AUTONOMIC CIRCUITS;
LOCOMOTOR-ACTIVITY
AB Background: The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV) Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons.
Methodology/Principal Findings: Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA) and gastrocnemius (GC). As revealed by combined immunocytochemistry and confocal microscopy, 24-32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32-40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals) were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8-12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells.
Conclusions/Significance: The study establishes the time window for virally - labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of the lumbar neural networks.
C1 [Jovanovic, Ksenija; O'Donovan, Michael J.] Natl Inst Neurol Disorders & Stroke, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Jovanovic, Ksenija] Hosp Nacl Paraplejicos, Lab Reparac Neural & Biomat, Toledo, Spain.
[Pastor, Angel M.] Univ Seville, Dept Fisiol & Zool, Fac Biol, Seville, Spain.
RP Jovanovic, K (reprint author), Natl Inst Neurol Disorders & Stroke, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM ODonovM@ninds.nih.gov
RI o'donovan, michael/A-2357-2015
OI o'donovan, michael/0000-0003-2487-7547
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, Maryland; MICINN-FEDER, Spain
[PET2008-0226, BFU2009-07121]
FX The study was funded by the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke, National Institutes of
Health, Bethesda, Maryland to Michael O'Donovan and the grants
PET2008-0226 and BFU2009-07121 from MICINN-FEDER, Spain to Angel M.
Pastor. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
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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 JUL 23
PY 2010
VL 5
IS 7
AR e11743
DI 10.1371/journal.pone.0011743
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 630AQ
UT WOS:000280243800017
PM 20668534
ER
PT J
AU Mangone, M
Manoharan, AP
Thierry-Mieg, D
Thierry-Mieg, J
Han, T
Mackowiak, SD
Mis, E
Zegar, C
Gutwein, MR
Khivansara, V
Attie, O
Chen, K
Salehi-Ashtiani, K
Vidal, M
Harkins, TT
Bouffard, P
Suzuki, Y
Sugano, S
Kohara, Y
Rajewsky, N
Piano, F
Gunsalus, KC
Kim, JK
AF Mangone, Marco
Manoharan, Arun Prasad
Thierry-Mieg, Danielle
Thierry-Mieg, Jean
Han, Ting
Mackowiak, Sebastian D.
Mis, Emily
Zegar, Charles
Gutwein, Michelle R.
Khivansara, Vishal
Attie, Oliver
Chen, Kevin
Salehi-Ashtiani, Kourosh
Vidal, Marc
Harkins, Timothy T.
Bouffard, Pascal
Suzuki, Yutaka
Sugano, Sumio
Kohara, Yuji
Rajewsky, Nikolaus
Piano, Fabio
Gunsalus, Kristin C.
Kim, John K.
TI The Landscape of C. elegans 3 ' UTRs
SO SCIENCE
LA English
DT Article
ID HISTONE MESSENGER-RNA; CAENORHABDITIS-ELEGANS; GENOME; TRANSCRIPTOME;
MECHANISMS; EXPRESSION; WORMBASE; RESOURCE; BIOLOGY; PROTEIN
AB Three-prime untranslated regions (3'UTRs) of metazoan messenger RNAs (mRNAs) contain numerous regulatory elements, yet remain largely uncharacterized. Using polyA capture, 3' rapid amplification of complementary DNA (cDNA) ends, full-length cDNAs, and RNA-seq, we defined similar to 26,000 distinct 3'UTRs in Caenorhabditis elegans for similar to 85% of the 18,328 experimentally supported protein-coding genes and revised similar to 40% of gene models. Alternative 3'UTR isoforms are frequent, often differentially expressed during development. Average 3'UTR length decreases with animal age. Surprisingly, no polyadenylation signal (PAS) was detected for 13% of polyadenylation sites, predominantly among shorter alternative isoforms. Trans-spliced (versus non-trans-spliced) mRNAs possess longer 3'UTRs and frequently contain no PAS or variant PAS. We identified conserved 3'UTR motifs, isoform-specific predicted microRNA target sites, and polyadenylation of most histone genes. Our data reveal a rich complexity of 3'UTRs, both genome-wide and throughout development.
C1 [Mangone, Marco; Mis, Emily; Zegar, Charles; Gutwein, Michelle R.; Attie, Oliver; Chen, Kevin; Piano, Fabio; Gunsalus, Kristin C.] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA.
[Manoharan, Arun Prasad; Han, Ting; Khivansara, Vishal; Kim, John K.] Univ Michigan, Dept Human Genet, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Thierry-Mieg, Danielle; Thierry-Mieg, Jean] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Mackowiak, Sebastian D.; Chen, Kevin; Rajewsky, Nikolaus] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
[Salehi-Ashtiani, Kourosh; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Salehi-Ashtiani, Kourosh; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Salehi-Ashtiani, Kourosh; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Harkins, Timothy T.] Roche Appl Sci, Indianapolis, IN 46250 USA.
[Bouffard, Pascal] Roche Appl Sci, Life Sci 454, Branford, CT 06405 USA.
[Suzuki, Yutaka; Sugano, Sumio] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo 1088639, Japan.
[Kohara, Yuji] Natl Inst Genet, Ctr Genet Resource Informat, Genome Biol Lab, Mishima, Shizuoka 4118540, Japan.
[Piano, Fabio; Gunsalus, Kristin C.] NYU, Abu Dhabi, U Arab Emirates.
RP Piano, F (reprint author), NYU, Dept Biol, Ctr Genom & Syst Biol, 1009 Silver Ctr, New York, NY 10003 USA.
EM fp1@nyu.edu; kcg1@nyu.edu; jnkim@umich.edu
RI THIERRY-MIEG, Jean/F-1975-2017;
OI THIERRY-MIEG, Jean/0000-0002-0396-6789; Salehi-Ashtiani,
Kourosh/0000-0002-6521-5243; Mangone, Marco/0000-0001-7551-8793
FU NIH [U01-HG004276, R00HG004515, R01GM088565]; Ministry of Education,
Culture, Sports, Science and Technology of Japan; Muscular Dystrophy
Association; Pew Charitable Trusts; DFCI Strategic Initiative;
Helmholtz-Alliance on Systems Biology (Max Delbruck Centrum Systems
Biology Network); NIH; National Library of Medicine
FX This work was supported in part by grants from NIH (U01-HG004276) to F.
P., K. C. G., J.K.K., and N.R.; NIH grant (R00HG004515) to K. C.;
Grants-in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology of Japan to Y.K., S.S., and
Y.S.; NIH (R01GM088565), Muscular Dystrophy Association and the Pew
Charitable Trusts to J.K.K.; a gift from the Ellison Foundation to M. V.
and Institute Sponsored Research funds from the DFCI Strategic
Initiative in support of the CCSB; the Helmholtz-Alliance on Systems
Biology (Max Delbruck Centrum Systems Biology Network) to S. D. M.; and
the Intramural Research Program of NIH, National Library of Medicine to
J.T.-M. and D. T.-M. We thank J. V. Moran, T. Blumenthal, A. Billi, D.
Mecenas, and B. Bargmann for discussions; T. Shin'I and Exelixis for C.
elegans cDNA traces; and, for technical assistance, T. Nawy and B. Brown
(statistical analysis); R. Sachidanandam, R. Lyons, and S. Genik (deep
sequencing); P. MacMenamin and D. Schaub (3'UTRome database); M. Morris
(data submission); and L. Huang (stage analysis). 3'UTRome data sets are
available from NCBI Trace Archive, dbEST, Sequence Read Archive, Gene
Expression Omnibus, and modENCODE (8). See supporting online materials
and methods for details. Annotations are displayed at NCBI AceView
(www.aceview.org) (9) and www.UTRome.org (12).
NR 23
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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 JUL 23
PY 2010
VL 329
IS 5990
BP 432
EP 435
DI 10.1126/science.1191244
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 629KJ
UT WOS:000280196500035
PM 20522740
ER
PT J
AU Huson, HJ
Parker, HG
Runstadler, J
Ostrander, EA
AF Huson, Heather J.
Parker, Heidi G.
Runstadler, Jonathan
Ostrander, Elaine A.
TI A genetic dissection of breed composition and performance enhancement in
the Alaskan sled dog
SO BMC GENETICS
LA English
DT Article
ID MULTILOCUS GENOTYPE DATA; DOMESTIC DOG; INFERENCE; MULTIPLE; ORIGIN
AB Background: The Alaskan sled dog offers a rare opportunity to investigate the development of a dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped purebred dog breeds. Sled dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure.
Results: We observe that the Alaskan sled dog has a unique molecular signature and that the genetic profile is sufficient for identifying dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic.
Conclusion: We have established a genetic breed profile for the Alaskan sled dog, identified profile variance between sprint and distance dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled dog.
C1 [Huson, Heather J.; Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Huson, Heather J.; Runstadler, Jonathan] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA.
RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU NCRR [5P20RR016466]; National Human Genome Research Institute
FX We acknowledge the INBRE grant 5P20RR016466 from NCRR and we thank the
Intramural program of the National Human Genome Research Institute for
their support. We also thank Kenneth and Lori Chezik, Dr. Dawn Brown,
Greg Sellentin, and Deborah McGrath for sharing their expertise and
review of the performance phenotype rating criteria. We acknowledge Greg
Sellentin for his contribution of dog photos. We appreciate collection
assistance from Danielle Dillon, Keiko Herrick, Lori Gildehaus, Ian
Herriott, and the kennel owners and handlers and we gratefully
acknowledge the sled dog owners who have generously contributed
performance ratings and canine DNA samples to our study.
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PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD JUL 22
PY 2010
VL 11
AR 71
DI 10.1186/1471-2156-11-71
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 662BJ
UT WOS:000282781300001
PM 20649949
ER
PT J
AU Anatriello, E
Ribeiro, JMC
de Miranda-Santos, IKF
Brandao, LG
Anderson, JM
Valenzuela, JG
Maruyama, SR
Silva, JS
Ferreira, BR
AF Anatriello, Elen
Ribeiro, Jose M. C.
de Miranda-Santos, Isabel K. F.
Brandao, Lucinda G.
Anderson, Jennifer M.
Valenzuela, Jesus G.
Maruyama, Sandra R.
Silva, Joao S.
Ferreira, Beatriz R.
TI An insight into the sialotranscriptome of the brown dog tick,
Rhipicephalus sanguineus
SO BMC GENOMICS
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; HISTAMINE-BINDING PROTEINS; SALIVARY-GLAND
TRANSCRIPTS; PATHWAY INHIBITOR TFPI; BUG RHODNIUS-PROLIXUS; ADULT FEMALE
MOSQUITO; IXODES-SCAPULARIS; SOFT TICK; HAEMAPHYSALIS-LONGICORNIS;
DERMACENTOR-ANDERSONI
AB Background: Rhipicephalus sanguineus, known as the brown dog tick, is a common ectoparasite of domestic dogs and can be found worldwide. R. sanguineus is recognized as the primary vector of the etiological agent of canine monocytic ehrlichiosis and canine babesiosis. Here we present the first description of a R. sanguineus salivary gland transcriptome by the production and analysis of 2,034 expressed sequence tags (EST) from two cDNA libraries, one consctructed using mRNA from dissected salivary glands from female ticks fed for 3-5 days (early to mid library, RsSGL1) and the another from ticks fed for 5 days (mid library, RsSGL2), identifying 1,024 clusters of related sequences.
Results: Based on sequence similarities to nine different databases, we identified transcripts of genes that were further categorized according to function. The category of putative housekeeping genes contained similar to 56% of the sequences and had on average 2.49 ESTs per cluster, the secreted protein category contained 26.6% of the ESTs and had 2.47 EST's/clusters, while 15.3% of the ESTs, mostly singletons, were not classifiable, and were annotated as "unknown function". The secreted category included genes that coded for lipocalins, proteases inhibitors, disintegrins, metalloproteases, immunomodulatory and antiinflammatory proteins, as Evasins and Da-p36, as well as basic-tail and 18.3 kDa proteins, cement proteins, mucins, defensins and antimicrobial peptides. Comparison of the abundance of ESTs from similar contigs of the two salivary gland cDNA libraries allowed the identification of differentially expressed genes, such as genes coding for Evasins and a thrombin inhibitor, which were over expressed in the RsSGL1 (early to mid library) versus RsSGL2 (mid library), indicating their role in inhibition of inflammation at the tick feeding site from the very beginning of the blood meal. Conversely, sequences related to cement (64P), which function has been correlated with tick attachment, was largely expressed in the mid library.
Conclusions: Our survey provided an insight into the R. sanguineus sialotranscriptome, which can assist the discovery of new targets for anti-tick vaccines, as well as help to identify pharmacologically active proteins.
C1 [Ferreira, Beatriz R.] Univ Sao Paulo, Dept Maternal & Child & Publ Hlth Nursing, Ribeirao Preto Sch Nursing, BR-14049900 Ribeirao Preto, SP, Brazil.
[Anatriello, Elen; de Miranda-Santos, Isabel K. F.; Brandao, Lucinda G.; Maruyama, Sandra R.; Silva, Joao S.] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto, SP, Brazil.
[Ribeiro, Jose M. C.; Anderson, Jennifer M.; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[de Miranda-Santos, Isabel K. F.] Embrapa Recursos Genet & Biotecnol, BR-70770900 Brasilia, DF, Brazil.
[Brandao, Lucinda G.] Univ Paulista, BR-16018280 Aracatuba, SP, Brazil.
RP Ferreira, BR (reprint author), Univ Sao Paulo, Dept Maternal & Child & Publ Hlth Nursing, Ribeirao Preto Sch Nursing, BR-14049900 Ribeirao Preto, SP, Brazil.
EM brferrei@usp.br
RI Silva, Joao/A-4484-2008; Ferreira, Beatriz/C-2003-2012; Maruyama,
Sandra/G-1171-2012; de Miranda Santos, Isabel/B-7597-2012; Brandao,
Lenine/J-5334-2013; Anatriello, Elen/N-1429-2015; de Miranda Santos,
Isabel/D-5261-2016;
OI Ferreira, Beatriz/0000-0002-6781-2236; de Miranda Santos,
Isabel/0000-0002-0438-4430; Maruyama, Sandra/0000-0001-6807-1452;
Ribeiro, Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Fundacao de Amparo a
Pesquisa do Estado de Sao Paulo - FAPESP [2004/09992-7]; Conselho
Nacional de Desenvolvimento Cient fico e Tecnologico - CNPq
[130780/2005-7]
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, by the Fundacao de
Amparo a Pesquisa do Estado de Sao Paulo - FAPESP (2004/09992-7) and by
the Conselho Nacional de Desenvolvimento Cient fico e Tecnologico -
CNPq. E. A. was supported by a scholarship from CNPq (130780/2005-7).
The authors thank Dr. G. H. Bechara for the tick specimens used to
generate the RsSGL2 library (FCAV-UNESP), and Dr. A. E. Proudfoot and
Dr. A. Frauenschuh for some of the ESTs employed in the work. Because
J.M.C. Ribeiro is a government employee and this is a government work,
the work is in the public domain in the United States. Notwithstanding
any other agreements, the NIH reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices. You can
establish rights outside of the U.S. subject to a government use
license.
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 22
PY 2010
VL 11
AR 450
DI 10.1186/1471-2164-11-450
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 662DM
UT WOS:000282787400005
PM 20650005
ER
PT J
AU Suzuki, S
Urano, E
Hashimoto, C
Tsutsumi, H
Nakahara, T
Tanaka, T
Nakanishi, Y
Maddali, K
Han, Y
Hamatake, M
Miyauchi, K
Pommie, Y
Beutler, JA
Sugiura, W
Fuji, H
Hoshino, T
Itotani, K
Nomura, W
Narumi, T
Yamamoto, N
Komano, JA
Tamamura, H
AF Suzuki, Shintaro
Urano, Emiko
Hashimoto, Chic
Tsutsumi, Hiroshi
Nakahara, Toru
Tanaka, Tomohiro
Nakanishi, Yuta
Maddali, Kasthuraiah
Han, Yan
Hamatake, Makiko
Miyauchi, Kosuke
Pommie, Yves
Beutler, John A.
Sugiura, Wataru
Fuji, Hideyoshi
Hoshino, Tyuji
Itotani, Kyoko
Nomura, Wataru
Narumi, Tetsuo
Yamamoto, Naoki
Komano, Jun A.
Tamamura, Hirokazu
TI Peptide HIV-1 Integrase Inhibitors from HIV-1 Gene Products
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; PREINTEGRATION
COMPLEXES; VIRAL INTEGRASE; STRAND TRANSFER; PROTEIN; DESIGN; VPR;
CELLS; DNA
AB Anti-HIV peptides with inhibitory activity against HIV-1 integrase (IN) have been found in overlapping peptide libraries derived from HIV-1 gene products. In a strand transfer assay using IN, inhibitory active peptides with certain sequential motifs related to Vpr- and Env-derived peptides were found. The addition of an octa-arginyl group to the inhibitory peptides caused a remarkable inhibition of the strand transfer and 3'-end-processing reactions catalyzed by IN and significant inhibition against HIV replication.
C1 [Suzuki, Shintaro; Hashimoto, Chic; Tsutsumi, Hiroshi; Nakahara, Toru; Tanaka, Tomohiro; Nakanishi, Yuta; Itotani, Kyoko; Nomura, Wataru; Narumi, Tetsuo; Tamamura, Hirokazu] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Med Chem, Chiyoda Ku, Tokyo 1010062, Japan.
[Urano, Emiko; Han, Yan; Hamatake, Makiko; Miyauchi, Kosuke; Sugiura, Wataru; Yamamoto, Naoki; Komano, Jun A.] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan.
[Maddali, Kasthuraiah; Pommie, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fuji, Hideyoshi; Hoshino, Tyuji] Chiba Univ, Grad Sch Pharmaceut Sci, Dept Phys Chem, Inage Ku, Chiba 2638522, Japan.
[Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Tamamura, H (reprint author), Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Med Chem, Chiyoda Ku, 2-3-10 Kandasurugadai, Tokyo 1010062, Japan.
EM tarnamura.mr@tmd.ac.jp
RI Beutler, John/B-1141-2009; Nomura, Wataru/F-5812-2015; Tsutsumi,
Hiroshi/L-8761-2016;
OI Beutler, John/0000-0002-4646-1924; Tsutsumi,
Hiroshi/0000-0003-3780-7871; Nomura, Wataru/0000-0001-8348-7544
FU Ministry of Education, Culture, Sports, Science, and Technology of
Japan; Japanese Ministry of Health, Labor, and Welfare; National Cancer
Institute, Center for Cancer Research; JSPS
FX We thank Prof. A. Iwamoto's group of the Institute of Medical Science at
the University of Tokyo for the peptide libraries and Dr. M. Nicklaus
from NCI/NIH for providing the modeled structure of full-length HIV-1
IN. T.T. is supported by JSPS research fellowships for young scientists.
This work was supported in part by Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and Technology
of Japan, and Health and Labor Sciences Research Grants from Japanese
Ministry of Health, Labor, and Welfare. K.M. and Y.P. are supported by
the Intramural Program of the National Cancer Institute, Center for
Cancer Research.
NR 25
TC 23
Z9 23
U1 0
U2 5
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 JUL 22
PY 2010
VL 53
IS 14
BP 5356
EP 5360
DI 10.1021/jm1003528
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 623ZZ
UT WOS:000279787200026
PM 20586421
ER
PT J
AU Jin, X
Costa, RM
AF Jin, Xin
Costa, Rui M.
TI Start/stop signals emerge in nigrostriatal circuits during sequence
learning
SO NATURE
LA English
DT Article
ID DOPAMINE NEURONS ENCODE; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE;
SYNAPTIC PLASTICITY; BASAL GANGLIA; IN-VIVO; STRIATUM; REPRESENTATION;
PATTERN; TIME
AB Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson's and Huntington's diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.
C1 [Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-2780156 Oeiras, Portugal.
RP Costa, RM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM ruicosta@fchampalimaud.org
OI Costa, Rui/0000-0003-0495-8374
FU NIAAA Division of Intramural Clinical and Biological Research; Institute
Gulbenkian de Ciencia; European Research Council [243393]
FX We thank Y. Li for the RGS9-Cre mice, C. Gerfen for the TH-Cre mice, K.
Nakazawa for the NMDAR1-loxP mice, F. Tecuapetla and S. Lima for help in
the optogenetics experiment, G. Luo for genotyping, and D. Lovinger, G.
Cui, C. French, C. Gremel and E. Dias-Ferreira for comments on the
manuscript. This research was supported by the NIAAA Division of
Intramural Clinical and Biological Research, the Champalimaud
Neuroscience Programme at Institute Gulbenkian de Ciencia and European
Research Council Grant 243393 to R.M.C.
NR 40
TC 180
Z9 181
U1 3
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 457
EP 462
DI 10.1038/nature09263
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200028
PM 20651684
ER
PT J
AU Qi, HH
Sarkissian, M
Hu, GQ
Wang, ZB
Bhattacharjee, A
Gordon, DB
Gonzales, M
Lan, F
Ongusaha, PP
Huarte, M
Yaghi, NK
Lim, H
Garcia, BA
Brizuela, L
Zhao, KJ
Roberts, TM
Shi, Y
AF Qi, Hank H.
Sarkissian, Madathia
Hu, Gang-Qing
Wang, Zhibin
Bhattacharjee, Arindam
Gordon, D. Benjamin
Gonzales, Michelle
Lan, Fei
Ongusaha, Pat P.
Huarte, Maite
Yaghi, Nasser K.
Lim, Huijun
Garcia, Benjamin A.
Brizuela, Leonardo
Zhao, Keji
Roberts, Thomas M.
Shi, Yang
TI Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and
craniofacial development
SO NATURE
LA English
DT Article
ID LINKED MENTAL-RETARDATION; STRUCTURAL INSIGHTS; NERVOUS-SYSTEM; HUMAN
GENOME; CELL-CYCLE; GENES; TRANSCRIPTION; CHROMATIN; METHYLATION; FAMILY
AB X-linked mental retardation (XLMR) is a complex human disease that causes intellectual disability(1). Causal mutations have been found in approximately 90 X-linked genes(2); however, molecular and biological functions of many of these genetically defined XLMR genes remain unknown. PHF8 (PHD (plant homeo domain) finger protein 8) is a JmjC domain-containing protein and its mutations have been found in patients with XLMR and craniofacial deformities. Here we provide multiple lines of evidence establishing PHF8 as the first mono-methyl histone H4 lysine 20 (H4K20me1) demethylase, with additional activities towards histone H3K9me1 and me2. PHF8 is located around the transcription start sites (TSS) of similar to 7,000 RefSeq genes and in gene bodies and intergenic regions (non-TSS). PHF8 depletion resulted in upregulation of H4K20me1 and H3K9me1 at the TSS and H3K9me2 in the non-TSS sites, respectively, demonstrating differential substrate specificities at different target locations. PHF8 positively regulates gene expression, which is dependent on its H3K4me3-binding PHD and catalytic domains. Importantly, patient mutations significantly compromised PHF8 catalytic function. PHF8 regulates cell survival in the zebrafish brain and jaw development, thus providing a potentially relevant biological context for understanding the clinical symptoms associated with PHF8 patients. Lastly, genetic and molecular evidence supports a model whereby PHF8 regulates zebrafish neuronal cell survival and jaw development in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB, which functions downstream of multiple signalling and developmental pathways(3). Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR.
C1 [Qi, Hank H.; Lan, Fei; Huarte, Maite; Yaghi, Nasser K.; Lim, Huijun; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Qi, Hank H.; Lim, Huijun; Shi, Yang] Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA.
[Sarkissian, Madathia; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Hu, Gang-Qing; Wang, Zhibin; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Bhattacharjee, Arindam; Gordon, D. Benjamin; Brizuela, Leonardo] Agilent Technol, Santa Clara, CA 95051 USA.
[Gonzales, Michelle; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Ongusaha, Pat P.] Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA.
[Ongusaha, Pat P.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA.
RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM Thomas_Roberts@dfci.harvard.edu; yshi@hms.harvard.edu
RI HU, GANGQING/K-5849-2012; Huarte, Maite/J-6903-2014
OI Huarte, Maite/0000-0003-3753-6493
FU Ruth L. Kirschstein-National Service [T32 NS007473, T32 CA09031-32];
Harvard SHURP; Agency for Science, Technology and Research (A*STAR);
National Science Foundation [CBET-0941143]; NIH [GM 071004, NCI118487,
CA50661]; Ellison Foundation
FX We thank Shi laboratory members for helpful discussions and N.
Mosammaparast and S. Chen for providing the nucleosomes. We thank G.
Rosenfeld for sharing unpublished PHF8 results, and G. Rosenfeld, A.
Schier and P. Hinds for discussions. H.H.Q. is a recipient of Ruth L.
Kirschstein-National Service Research Award (T32 NS007473 and T32
CA09031-32). N.K.Y. was supported by Harvard SHURP (Summer Honors
Undergraduate Research Program). H.L. is a recipient of the Agency for
Science, Technology and Research (A*STAR) National Science Scholarship.
This work was supported by grants from the National Science Foundation
(CBET-0941143) to B.A.G.; NIH (GM 071004 and NCI118487) to Y. S.; a
Senior Scholar Grant from the Ellison Foundation, and an NIH PO1 grant
(CA50661) to T.M.R.
NR 39
TC 130
Z9 137
U1 3
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 503
EP U11
DI 10.1038/nature09261
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200039
PM 20622853
ER
PT J
AU Hamburg, MA
Collins, FS
AF Hamburg, Margaret A.
Collins, Francis S.
TI The Path to Personalized Medicine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Hamburg, Margaret A.] US FDA, Silver Spring, MD USA.
[Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Hamburg, MA (reprint author), US FDA, Silver Spring, MD USA.
NR 5
TC 593
Z9 608
U1 19
U2 199
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 JUL 22
PY 2010
VL 363
IS 4
BP 301
EP 304
DI 10.1056/NEJMp1006304
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 628RU
UT WOS:000280139300001
PM 20551152
ER
PT J
AU Kumar, R
Seibold, MA
Aldrich, MC
Williams, LK
Reiner, AP
Colangelo, L
Galanter, J
Gignoux, C
Hu, DL
Sen, S
Choudhry, S
Peterson, EL
Rodriguez-Santana, J
Rodriguez-Cintron, W
Nalls, MA
Leak, TS
O'Meara, E
Meibohm, B
Kritchevsky, SB
Li, RL
Harris, TB
Nickerson, DA
Fornage, M
Enright, P
Ziv, E
Smith, LJ
Liu, KA
Gonzalez-Burchard, E
AF Kumar, Rajesh
Seibold, Max A.
Aldrich, Melinda C.
Williams, L. Keoki
Reiner, Alex P.
Colangelo, Laura
Galanter, Joshua
Gignoux, Christopher
Hu, Donglei
Sen, Saunak
Choudhry, Shweta
Peterson, Edward L.
Rodriguez-Santana, Jose
Rodriguez-Cintron, William
Nalls, Michael A.
Leak, Tennille S.
O'Meara, Ellen
Meibohm, Bernd
Kritchevsky, Stephen B.
Li, Rongling
Harris, Tamara B.
Nickerson, Deborah A.
Fornage, Myriam
Enright, Paul
Ziv, Elad
Smith, Lewis J.
Liu, Kiang
Gonzalez-Burchard, Esteban
TI Genetic Ancestry in Lung-Function Predictions
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID AFRICAN-AMERICANS; POPULATION-STRUCTURE; PULMONARY-FUNCTION;
NATURAL-HISTORY; ADMIXTURE; RACE; ASTHMA; DISEASE; HEALTH; PREVALENCE
AB BACKGROUND
Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American.
METHODS
We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations.
RESULTS
African ancestry was inversely related to forced expiratory volume in 1 second (FEV(1)) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants.
CONCLUSIONS
Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity.
C1 [Kumar, Rajesh] Childrens Mem Hosp, Div Allergy & Immunol, Chicago, IL 60614 USA.
[Colangelo, Laura; Smith, Lewis J.; Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Seibold, Max A.] Natl Jewish Hlth, Denver, CO USA.
[Aldrich, Melinda C.; Galanter, Joshua; Gignoux, Christopher; Hu, Donglei; Sen, Saunak; Choudhry, Shweta; Ziv, Elad; Gonzalez-Burchard, Esteban] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Williams, L. Keoki; Peterson, Edward L.] Henry Ford Hlth Syst, Detroit, MI USA.
[Reiner, Alex P.; O'Meara, Ellen; Nickerson, Deborah A.] Univ Washington, Seattle, WA 98195 USA.
[Rodriguez-Santana, Jose] Pediat Pulm Program San Juan, San Juan, PR USA.
[Rodriguez-Cintron, William] Univ Puerto Rico, Sch Med, San Juan Vet Affairs Med Ctr, San Juan, PR 00936 USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Meibohm, Bernd] Univ Tennessee, Hlth Sci Ctr, Coll Pharm, Memphis, TN USA.
[Li, Rongling] Univ Tennessee, Hlth Sci Ctr, Coll Med, Memphis, TN USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX USA.
[Enright, Paul] Univ Arizona, Coll Publ Hlth, Tucson, AZ USA.
RP Kumar, R (reprint author), Childrens Mem Hosp, Div Allergy & Immunol, 2300 Childrens Plaza,Box 60, Chicago, IL 60614 USA.
EM rkumar@childrensmemorial.org
RI Aldrich, Melinda/C-7783-2013; Ziv, Elad/L-5396-2014;
OI Smith, Lewis J/0000-0002-4728-1562; Kritchevsky,
Stephen/0000-0003-3336-6781; Galanter, Joshua/0000-0002-2561-6384
FU National Heart, Lung, and Blood Institute (NHLBI), National Institutes
of Health (NIH) [N01-HC-48047, N01-HC-48050, N01-HC-95095]; NIH
[HL078885, HL088133, AI077439, ES015794, K23HL093023-01, R01 HL71862,
R01 HL71017, R01 AG032136, R01 AI79139, R01 AI61774, R01 HL79055];
Robert Wood Johnson Foundation Amos Medical Faculty; Flight Attendant
Medical Research Institute; American Asthma Foundation; Tobacco-Related
Disease Research Program [15KT-0008]; NHLBI [N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295]; National Institute of Neurological Disorders and Stroke;
National Institute on Aging (NIA), Longevity Consortium [U19 AG023122,
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Center for
Research Resources [U54-RR020278]
FX Supported by contracts (N01-HC-48047 through 48050 and N01-HC-95095)
from the National Heart, Lung, and Blood Institute (NHLBI), National
Institutes of Health (NIH), as well as grants from the NIH (HL078885,
HL088133, AI077439, and ES015794, to Dr. Burchard; K23HL093023-01, to
Dr. Kumar; R01 HL71862, R01 HL71017, and R01 AG032136, to Dr. Reiner;
and R01 AI79139, R01 AI61774, and R01 HL79055, to Dr. Williams), the
Robert Wood Johnson Foundation Amos Medical Faculty Development Program
and the Flight Attendant Medical Research Institute (to Dr. Burchard),
the American Asthma Foundation (to Dr. Williams), and the
Tobacco-Related Disease Research Program (New Investigator Award
15KT-0008, to Dr. Choudhry). The CHS was supported by NHLBI grants
(N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, and U01 HL080295), with additional
funding from the National Institute of Neurological Disorders and Stroke
and a grant from the National Institute on Aging (NIA) (U19 AG023122
from the Longevity Consortium). The CARe Consortium was supported in
part by a grant from the NHLBI (with a full description of the funding
available at
http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx). Health ABC
was supported in part by the Intramural Research Program of the NIH and
by the NIA, through contracts (N01-AG-6-2101, N01-AG-6-2103, and
N01-AG-6-2106), and by a grant from the National Center for Research
Resources (U54-RR020278) for the genotyping.
NR 47
TC 92
Z9 93
U1 0
U2 8
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 JUL 22
PY 2010
VL 363
IS 4
BP 321
EP 330
DI 10.1056/NEJMoa0907897
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 628RU
UT WOS:000280139300005
PM 20647190
ER
PT J
AU Al-Souhibani, N
Al-Ahmadi, W
Hesketh, JE
Blackshear, PJ
Khabar, KSA
AF Al-Souhibani, N.
Al-Ahmadi, W.
Hesketh, J. E.
Blackshear, P. J.
Khabar, K. S. A.
TI The RNA-binding zinc-finger protein tristetraprolin regulates AU-rich
mRNAs involved in breast cancer-related processes
SO ONCOGENE
LA English
DT Article
DE posttranscriptional control; AU-rich elements; RNA-binding proteins; RNA
stability; tristetraprolin
ID UROKINASE PLASMINOGEN-ACTIVATOR; ENDOTHELIAL GROWTH-FACTOR;
POSTTRANSCRIPTIONAL REGULATION; PROGNOSTIC-FACTOR; GENE-EXPRESSION; HUR;
RECEPTOR; ELEMENTS; CELL; CYCLOOXYGENASE-2
AB Tristetraprolin (TTP or ZFP36) is a tandem CCCH zinc-finger RNA-binding protein that regulates the stability of certain AU-rich element (ARE) mRNAs. Recent work suggests that TTP is deficient in cancer cells when compared with normal cell types. In this study we found that TTP expression was lower in invasive breast cancer cells (MDAMB231) compared with normal breast cell lines MCF12A and MCF-10. TTP targets were probed using a novel approach by expressing the C124R zinc-finger TTP mutant that functions as dominant negative and increases target mRNA expression. In contrast to wild-type TTP, C124R TTP was able to increase certain ARE-mRNA expressions in serum-stimulated breast cancer cells. Using an ARE-gene microarray, novel targets of TTP regulation were identified, namely, urokinase plasminogen activator (uPA), uPA receptor and matrix metalloproteinase-1, all known to have prominent roles in breast cancer invasion and metastasis. Expression of these targets was upregulated in tumorigenic types, particularly in highly invasive MDAMB231. The mRNA half-lives of these TTP-regulated genes were increased in TTP-knockout embryonic mouse fibroblasts, as assessed using real-time polymerase chain reaction, whereas forced restoration of TTP by transfection led to a reduction in their mRNA levels. RNA immunoprecipitation confirmed an association of TTP, but not C124R, with these target transcripts. Moreover, TTP reduced, whereas the mutant C124R TTP increased, the activity of reporter constructs fused to target ARE. As a result of TTP regulation, invasiveness of MDAMB231 cells was reduced. The data suggest that TTP, in a 30 untranslated region- and ARE-dependent manner, regulates an important subset of cancer-related genes that are involved in cellular growth, invasion and metastasis. Oncogene ( 2010) 29, 4205-4215; doi: 10.1038/onc.2010.168; published online 24 May 2010
C1 [Al-Souhibani, N.; Al-Ahmadi, W.; Khabar, K. S. A.] King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, Riyadh 11211, Saudi Arabia.
[Hesketh, J. E.] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Blackshear, P. J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA.
RP Khabar, KSA (reprint author), King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, P3354, Riyadh 11211, Saudi Arabia.
EM khabar@kfshrc.edu.sa
RI Khabar, Khalid/A-4772-2011
OI Khabar, Khalid/0000-0003-1003-9788
FU King Khalid Foundation, Riyadh
FX This study is a part of the Newcastle University doctoral thesis
requirements of NA-S. NA-S was supported by a PhD scholarship from King
Khalid Foundation, Riyadh. We acknowledge Dr Wi S Lai for TTP plasmids
and for the knockout MEF line. We also acknowledge Mr Maher Al-Saif for
his technical assistance.
NR 45
TC 51
Z9 51
U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUL 22
PY 2010
VL 29
IS 29
BP 4205
EP 4215
DI 10.1038/onc.2010.168
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 628VL
UT WOS:000280151500008
PM 20498646
ER
PT J
AU Peercy, BE
Sherman, AS
AF Peercy, Bradford E.
Sherman, Arthur S.
TI How Pancreatic beta-Cells Discriminate Long and Short Timescale cAMP
Signals
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; DEPENDENT PROTEIN-KINASE;
GLUCAGON-LIKE PEPTIDE-1; ADENYLYL-CYCLASE; AMP; CA2+; OSCILLATIONS;
DIFFUSION; COMPARTMENTS; ACTIVATION
AB The translocation of catalytic protein kinase A (cPKA) in response to cyclic-adenosine mono-phosphate (cAMP) depends on the pattern of stimulus applied to the cell. Experiments with IBMX have shown that 1), sustained cAMP elevation is more effective than oscillations of cAMP at getting cPKA into the nucleus; and 2), cPKA enters the nucleus by diffusion. We constructed mathematical models of cAMP activation of cPKA and their diffusion in order to study nuclear translocation of cPKA, and conclude that hindered diffusion of cPKA through the nuclear membrane by a rapid-binding process, but not globally reduced diffusion, can explain the experimental data: Perturbation analysis suggests that normal physiological oscillations of glucose would not result in nuclear translocation, but chronically high glucose that produces extended calcium plateaus and/or chronic glucagonlike peptide-1 stimulation could result in elevated levels of nuclear cPKA.
C1 [Sherman, Arthur S.] NIDDK, NIH, Neurosci Ctr Excellence, Bethesda, MD 20892 USA.
[Peercy, Bradford E.] Univ Maryland, Dept Math & Stat, Baltimore, MD 21201 USA.
RP Sherman, AS (reprint author), NIDDK, NIH, Neurosci Ctr Excellence, Bethesda, MD 20892 USA.
EM asherman@nih.gov
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases
FX A.S. was supported and B.P. supported (in part) by the Intramural
Research Program of the National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 30
TC 1
Z9 1
U1 0
U2 2
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 JUL 21
PY 2010
VL 99
IS 2
BP 398
EP 406
DI 10.1016/j.bpj.2010.04.043
PG 9
WC Biophysics
SC Biophysics
GA 629GD
UT WOS:000280182300011
PM 20643057
ER
PT J
AU Jung, HH
Jung, HJ
Milescu, M
Lee, CW
Lee, S
Lee, JY
Eu, YJ
Kim, HH
Swartz, KJ
Kim, JI
AF Jung, Hyun Ho
Jung, Hoi Jong
Milescu, Mirela
Lee, Chul Won
Lee, Seungkyu
Lee, Ju Yeon
Eu, Young-Jae
Kim, Ha Hyung
Swartz, Kenton J.
Kim, Jae Il
TI Structure and Orientation of a Voltage-Sensor Toxin in Lipid Membranes
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DEPENDENT K+ CHANNEL; GATING MODIFIER; TARANTULA TOXINS;
SODIUM-CHANNELS; MOLECULAR DETERMINANTS; PENETRATION DEPTH; SCORPION
TOXIN; ZINC FINGERS; SPIDER VENOM; ION CHANNELS
AB Amphipathic protein toxins from tarantula venom inhibit voltage-activated potassium (Kv) channels by binding to a critical helix-turn-helix motif termed the voltage sensor paddle. Although these toxins partition into membranes to bind the paddle motif, their structure and orientation within the membrane are unknown. We investigated the interaction of a tarantula toxin named SGTx with membranes using both fluorescence and NMR spectroscopy. Depth-dependent fluorescence-quenching experiments with brominated lipids suggest that Trp(30) in SGTx is positioned -9 A from the center of the bilayer. NMR spectra reveal that the inhibitor cystine knot structure of the toxin does not radically change upon membrane partitioning. Transferred cross-saturation NMR experiments indicate that the toxin's hydrophobic protrusion contacts the hydrophobic core of the membrane, whereas most surrounding polar residues remain at interfacial regions of the bilayer. The inferred orientation of the toxin reveals a twofold symmetry in the arrangement of basic and hydrophobic residues, a feature that is conserved among tarantula toxins. These results have important implications for regions of the toxin involved in recognizing membranes and voltage-sensor paddles, and for the mechanisms by which tarantula toxins alter the activity of different types of ion channels.
C1 [Jung, Hyun Ho; Jung, Hoi Jong; Lee, Seungkyu; Lee, Ju Yeon; Eu, Young-Jae; Kim, Jae Il] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
[Milescu, Mirela; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lee, Chul Won] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
[Lee, Chul Won] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Kim, Ha Hyung] Chung Ang Univ, Coll Pharm, Seoul 156756, South Korea.
RP Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
EM jikim@gist.ac.kr
FU 21st Century Frontier Research Program [M103KV010006-06K2201-00610];
Ministry of Health and Welfare, Republic of Korea [A080712]; National
Institute of Neurological Disorders and Stroke, National Institutes of
Health, Bethesda, MD
FX This study was supported by grants from the Brain Research Center of the
21st Century Frontier Research Program (M103KV010006-06K2201-00610), the
BioImaging Research Center at the Gwangju Institute of Science and
Technology, the Korea Healthcare technology R & D Project, Ministry of
Health and Welfare, Republic of Korea (A080712), and the Intramural
Research Program within the National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, MD.
NR 56
TC 16
Z9 17
U1 1
U2 5
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 JUL 21
PY 2010
VL 99
IS 2
BP 638
EP 646
DI 10.1016/j.bpj.2010.04.061
PG 9
WC Biophysics
SC Biophysics
GA 629GD
UT WOS:000280182300038
PM 20643084
ER
PT J
AU Barda-Saad, M
Shirasu, N
Pauker, MH
Hassan, N
Perl, O
Balbo, A
Yamaguchi, H
Houtman, JCD
Appella, E
Schuck, P
Samelson, LE
AF Barda-Saad, Mira
Shirasu, Naoto
Pauker, Maor H.
Hassan, Nirit
Perl, Orly
Balbo, Andrea
Yamaguchi, Hiroshi
Houtman, Jon C. D.
Appella, Ettore
Schuck, Peter
Samelson, Lawrence E.
TI Cooperative interactions at the SLP-76 complex are critical for actin
polymerization
SO EMBO JOURNAL
LA English
DT Article
DE actin polymerization; lymphocyte activation; signalling complexes;
SLP-76
ID T-CELL-RECEPTOR; APC CONTACT SITE; SIGNAL-TRANSDUCTION; ANTIGEN
RECEPTOR; ADAPTER PROTEIN; PHOSPHOLIPASE C-GAMMA-1; IMMUNOLOGICAL
SYNAPSE; IMMUNE SYNAPSE; ACTIVATION; CYTOSKELETON
AB T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1: Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation. The EMBO Journal (2010) 29, 2315-2328. doi:10.1038/emboj.2010.133; Published online 18 June 2010
C1 [Barda-Saad, Mira; Pauker, Maor H.; Hassan, Nirit; Perl, Orly] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[Shirasu, Naoto; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Balbo, Andrea; Schuck, Peter] NIH, Lab Bioengn & Phys Sci, NIBIB, Bethesda, MD 20892 USA.
[Yamaguchi, Hiroshi; Appella, Ettore] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Houtman, Jon C. D.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
RP Barda-Saad, M (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Bldg 204,Rm 210, IL-52900 Ramat Gan, Israel.
EM bardasm@mail.biu.ac.il
OI Schuck, Peter/0000-0002-8859-6966
FU NCI; NIBIB, NIH; Israel Science Foundation [971/08, 1659/08]
FX We thank Dr Alex Braiman for his help with the calcium measurement
analysis and Uriel Kaaro for his help in the operation of the FACS
sorting. This work was supported, in part, by the Intramural Research
Program of NCI and NIBIB, NIH and in part by the Israel Science
Foundation (grants no. 971/08 and 1659/08).
NR 55
TC 61
Z9 61
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD JUL 21
PY 2010
VL 29
IS 14
BP 2315
EP 2328
DI 10.1038/emboj.2010.133
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 628UP
UT WOS:000280148500008
PM 20562827
ER
PT J
AU Folkers, GK
Fauci, AS
AF Folkers, Gregory K.
Fauci, Anthony S.
TI Controlling and Ultimately Ending the HIV/AIDS Pandemic A Feasible Goal
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ANTIRETROVIRAL THERAPY; PROSPECTIVE COHORT; LIFE EXPECTANCY; HIV;
TRANSMISSION; INDIVIDUALS
C1 [Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A-03,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 15
TC 17
Z9 18
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 21
PY 2010
VL 304
IS 3
BP 350
EP 351
DI 10.1001/jama.2010.957
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 628HV
UT WOS:000280107500029
PM 20639573
ER
PT J
AU Dagdug, L
Vazquez, MV
Berezhkovskii, AM
Bezrukov, SM
AF Dagdug, Leonardo
Vazquez, Marco-Vinicio
Berezhkovskii, Alexander M.
Bezrukov, Sergey M.
TI Unbiased diffusion in tubes with corrugated walls
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID TRANSPORT
AB This study is devoted to unbiased motion of a point Brownian particle in a tube with corrugated walls made of conical sections of a varying length. Effective one-dimensional description in terms of the generalized Fick-Jacobs equation is used to derive a formula which gives the effective diffusion coefficient of the particle as a function of the geometric parameters of the tube. Comparison with the results of Brownian dynamics simulations allows us to establish the domain of applicability of both the one-dimensional description and the formula for the effective diffusion coefficient. (C) 2010 American Institute of Physics. [doi:10.1063/1.3431756]
C1 [Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Dagdug, Leonardo; Vazquez, Marco-Vinicio] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico.
RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM bezrukos@mail.nih.gov
FU NIH, Center for Information Technology; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This study was supported by the Intramural Research Program of the NIH,
Center for Information Technology, and Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 19
TC 28
Z9 28
U1 0
U2 6
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUL 21
PY 2010
VL 133
IS 3
AR 034707
DI 10.1063/1.3431756
PG 3
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 634QB
UT WOS:000280596900048
PM 20649350
ER
PT J
AU Ryabov, Y
Gutina, A
Feldman, Y
Frunza, S
Frunza, L
Schonhals, A
AF Ryabov, Yaroslav
Gutina, Anna
Feldman, Yuri
Frunza, Stefan
Frunza, Ligia
Schoenhals, Andreas
TI Comment on "Investigating hydration dependence of dynamics of confined
water: Monolayer, hydration water, and Maxwell-Wagner processes" [J.
Chem. Phys. 128, 154503 (2008)]
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Editorial Material
ID DIELECTRIC-RELAXATION; ROTATIONAL FLUCTUATIONS; MOLECULAR-SIEVES; POROUS
GLASSES; SYSTEMS
C1 [Ryabov, Yaroslav] NIH, Ctr Informat Technol, Div Computat Biosci, Bethesda, MD 20892 USA.
[Gutina, Anna; Feldman, Yuri] Hebrew Univ Jerusalem, Dept Appl Phys, IL-91904 Jerusalem, Israel.
[Frunza, Stefan; Frunza, Ligia] Natl Inst Mat Phys, R-077125 Magurele, Romania.
[Schoenhals, Andreas] BAM Fed Inst Mat Res & Testing, D-12200 Berlin, Germany.
RP Ryabov, Y (reprint author), NIH, Ctr Informat Technol, Div Computat Biosci, 12A-2041,South Dr,MSC 5624, Bethesda, MD 20892 USA.
EM yurif@vms.huji.ac.il
RI Schoenhals, Andreas/E-4194-2010; Frunza, Ligia/C-3923-2011; Frunza,
Stefan/C-3920-2011
NR 14
TC 5
Z9 5
U1 1
U2 14
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUL 21
PY 2010
VL 133
IS 3
AR 037101
DI 10.1063/1.3451102
PG 2
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 634QB
UT WOS:000280596900060
PM 20649362
ER
PT J
AU Michan, S
Li, Y
Chou, MMH
Parrella, E
Ge, HY
Long, JM
Allard, JS
Lewis, K
Miller, M
Xu, W
Mervis, RF
Chen, J
Guerin, KI
Smith, LEH
McBurney, MW
Sinclair, DA
Baudry, M
de Cabo, R
Longo, VD
AF Michan, Shaday
Li, Ying
Chou, Maggie Meng-Hsiu
Parrella, Edoardo
Ge, Huanying
Long, Jeffrey M.
Allard, Joanne S.
Lewis, Kaitlyn
Miller, Marshall
Xu, Wei
Mervis, Ronald F.
Chen, Jing
Guerin, Karen I.
Smith, Lois E. H.
McBurney, Michael W.
Sinclair, David A.
Baudry, Michel
de Cabo, Rafael
Longo, Valter D.
TI SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CALORIE RESTRICTION; TRANSCRIPTION FACTOR; CELL-SURVIVAL; DEACETYLASE
SIRT1; DENDRITIC GROWTH; MEMORY FORMATION; GENE-EXPRESSION; KNOCKOUT
MICE; C-REL; BRAIN
AB Conservation of normal cognitive functions relies on the proper performance of the nervous system at the cellular and molecular level. The mammalian nicotinamide-adenine dinucleotide-dependent deacetylase SIRT1 impacts different processes potentially involved in the maintenance of brain integrity, such as chromatin remodeling, DNA repair, cell survival, and neurogenesis. Here we show that SIRT1 is expressed in neurons of the hippocampus, a key structure in learning and memory. Using a combination of behavioral and electro-physiological paradigms, we analyzed the effects of SIRT1 deficiency and overexpression on mouse learning and memory as well as on synaptic plasticity. We demonstrated that the absence of SIRT1 impaired cognitive abilities, including immediate memory, classical conditioning, and spatial learning. In addition, we found that the cognitive deficits in SIRT1 knock-out (KO) mice were associated with defects in synaptic plasticity without alterations in basal synaptic transmission or NMDA receptor function. Brains of SIRT1-KO mice exhibited normal morphology and dendritic spine structure but displayed a decrease in dendritic branching, branch length, and complexity of neuronal dendritic arbors. Also, a decrease in extracellular signal-regulated kinase 1/2 phosphorylation and altered expression of hippocampal genes involved in synaptic function, lipid metabolism, and myelination were detected in SIRT1-KO mice. In contrast, mice with high levels of SIRT1 expression in brain exhibited regular synaptic plasticity and memory. We conclude that SIRT1 is indispensable for normal learning, memory, and synaptic plasticity in mice.
C1 [Longo, Valter D.] Univ So Calif, Andrus Gerontol Ctr, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA.
[Michan, Shaday; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs, Boston, MA 02115 USA.
[Chen, Jing; Guerin, Karen I.; Smith, Lois E. H.] Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
[Michan, Shaday] Inst Nacl Salud, Inst Geriatria, Mexico City 04510, DF, Mexico.
[Li, Ying; Chou, Maggie Meng-Hsiu; Xu, Wei; Baudry, Michel; Longo, Valter D.] Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA.
[Li, Ying; Parrella, Edoardo; Ge, Huanying; Longo, Valter D.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Mervis, Ronald F.] Univ S Florida, Coll Med, Dept Neurosurg & Brain Repair, Ctr Excellence Aging & Brain Repair, Tampa, FL 33612 USA.
[Mervis, Ronald F.] NeuroStruct Res Labs Inc, Tampa, FL 33137 USA.
[McBurney, Michael W.] Univ Ottawa, Dept Med, Ottawa Hlth Res Inst, Ottawa, ON K1H 8M5, Canada.
RP Longo, VD (reprint author), Univ So Calif, Andrus Gerontol Ctr, Dept Mol & Computat Biol, 3715 McClintock Ave, Los Angeles, CA 90089 USA.
EM decabora@grc.nia.nih.gov; vlongo@usc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Sinclair,
David/0000-0002-9936-436X; , rafael/0000-0003-2830-5693
FU University of Southern California National Institutes of Health (NIH)
Alzheimer's Disease Research Center; The Intramural Research Program of
the NIH/National Institute on Aging (NIA); Canadian Institutes of Health
Research; Juvenile Diabetes Research Foundation; Children's Hospital
Boston, Manton Center; NIH/NIA; NIH/National Institute of Neurological
Disorders and Stroke; NIH/National Eye Institute [EY017017, EY017017
04S1]; Glenn Foundation for Medical Research to Harvard Medical School
FX This research was supported by the University of Southern California
National Institutes of Health (NIH) Alzheimer's Disease Research Center
(V.D.L.), The Intramural Research Program of the NIH/National Institute
on Aging (NIA) (R.d.C.), the Canadian Institutes of Health Research
(M.W.M.), Juvenile Diabetes Research Foundation and Children's Hospital
Boston, Manton Center (J.C.), and grants from NIH/NIA and NIH/National
Institute of Neurological Disorders and Stroke (D.A.S.), NIH/National
Eye Institute (EY017017 and EY017017 04S1), Roche Foundation for Anemia
Research, and the MacTel Foundation (L.E.H.S.).D.A.S.is a senior scholar
of the Ellison Medical Foundation. The mouse transgenic and behavioral
work was supported by a gift from the Glenn Foundation for Medical
Research to Harvard Medical School.
NR 67
TC 145
Z9 154
U1 5
U2 19
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 JUL 21
PY 2010
VL 30
IS 29
BP 9695
EP 9707
DI 10.1523/JNEUROSCI.0027-10.2010
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 629NL
UT WOS:000280206500006
PM 20660252
ER
PT J
AU Kazanis, I
Lathia, JD
Vadakkan, TJ
Raborn, E
Wan, RQ
Mughal, MR
Eckley, DM
Sasaki, T
Patton, B
Mattson, MP
Hirschi, KK
Dickinson, ME
Ffrench-Constant, C
AF Kazanis, Ilias
Lathia, Justin D.
Vadakkan, Tegy J.
Raborn, Eric
Wan, Ruiqian
Mughal, Mohamed R.
Eckley, D. Mark
Sasaki, Takako
Patton, Bruce
Mattson, Mark P.
Hirschi, Karen K.
Dickinson, Mary E.
Ffrench-Constant, Charles
TI Quiescence and Activation of Stem and Precursor Cell Populations in the
Subependymal Zone of the Mammalian Brain Are Associated with Distinct
Cellular and Extracellular Matrix Signals
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ADULT SUBVENTRICULAR ZONE; NEUROGENIC REGIONS; VASCULAR NICHE; DENTATE
GYRUS; GERMINAL ZONE; TENASCIN-C; FOREBRAIN; GROWTH; MOUSE; INTEGRINS
AB The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularized compared to non-neurogenic periventricular areas, within which NSCs and precursors exhibit distinct behavior. Here, we investigate the possible mechanisms by which extracellular matrix molecules and their receptors might regulate this differential behavior. We show that NSCs and precursors proceed through mitosis in the same domains within the SEZ of adult male mice-albeit with NSCs nearer ependymal cells-and that distance from the ventricle is a stronger limiting factor for neurogenic activity than distance from blood vessels. Furthermore, we show that NSCs and precursors are embedded in a laminin-rich extracellular matrix, to which they can both contribute. Importantly, they express differential levels of extracellular matrix receptors, withNSCsexpressing low levels of alpha 6 beta 1 integrin, syndecan-1, and lutheran, and in vivo blocking of beta 1 integrin selectively induced the proliferation and ectopic migration of precursors. Finally, when NSCs are activated to reconstitute the niche after depletion of precursors, expression of laminin receptors is upregulated. These results indicate that the distinct behavior of adult NSCs and precursors is not necessarily regulated via exposure to differential extracellular signals, but rather via intrinsic regulation of their interaction with their microenvironment.
C1 [Kazanis, Ilias; Lathia, Justin D.; Ffrench-Constant, Charles] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Lathia, Justin D.; Wan, Ruiqian; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Vadakkan, Tegy J.; Dickinson, Mary E.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA.
[Raborn, Eric; Hirschi, Karen K.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Raborn, Eric; Hirschi, Karen K.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Raborn, Eric; Hirschi, Karen K.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Sasaki, Takako] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Patton, Bruce] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA.
[Ffrench-Constant, Charles] Queens Med Res Inst, Ctr Regenerat Med, MRC, Edinburgh EH16 4TJ, Midlothian, Scotland.
[Eckley, D. Mark] NIA, Genet Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Kazanis, I (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM ik255@cam.ac.uk
RI KAZANIS, ILIAS/B-5198-2011; Mattson, Mark/F-6038-2012; Eckley,
Mark/M-3526-2014;
OI Eckley, Mark/0000-0003-2296-5164; KAZANIS, ILIAS/0000-0003-1035-0584
FU National Institutes of Health (NIH) [NS40759]; National Science
Foundation [9876771]; Wellcome Trust and the Medical Research Council;
National Institute of Biomedical Imaging and Bioengineering Quantum
[1P20EB00706]; National Institute on Aging Intramural Research Program
FX J.D.L. was supported by the National Institutes of Health
(NIH)-Cambridge Graduate Partnership Program. B.L.P. is supported by
grants from the NIH (NS40759) and National Science Foundation (9876771).
C.ff.-C. is supported by the Wellcome Trust and the Medical Research
Council. This work was supported by the National Institutes of
Health-National Institute of Biomedical Imaging and Bioengineering
Quantum Grant Project (1P20EB00706) and the National Institute on Aging
Intramural Research Program. We thank Dr. Badrinath Roysam for sharing
the FARSIGHT software and Dr. L. Sorokin (University of Lund, Lund,
Sweden) and Dr. J. Miner (Washington University, St. Louis, MO) for the
kind offer of antibodies.
NR 51
TC 85
Z9 87
U1 1
U2 8
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 JUL 21
PY 2010
VL 30
IS 29
BP 9771
EP 9781
DI 10.1523/JNEUROSCI.0700-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 629NL
UT WOS:000280206500013
PM 20660259
ER
PT J
AU Guerrerio, AL
Berg, JM
AF Guerrerio, Anthony L.
Berg, Jeremy M.
TI Design of Single-Stranded Nucleic Acid Binding Peptides Based on
Nucleocapsid CCHC-Box Zinc-Binding Domains
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID UNIVERSAL MINICIRCLE SEQUENCE; MINIMAL ACTIVE DOMAIN; MURINE
LEUKEMIA-VIRUS; DNA-BINDING; IMMUNODEFICIENCY-VIRUS; FINGER PROTEIN; NMR
STRUCTURE; TRANSCRIPTION FACTORS; KINETOPLAST DNA; PENTANUCLEOTIDE
D(ACGCC)
AB The solution structures of nucleocapsid (NC)-like CCHC zinc-binding domains bound to nucleic acid targets have revealed that these domains bind guanosine residues within single-stranded nucleic acids. Here, we have performed initial studies examining the potential use of NC-like CCHC zinc-binding domains as modules to construct single-stranded nucleic acid binding peptides. The affinity for guanosine-containing single-stranded deoxyribooligonucleotides increases with the number of CCHC domains in the peptide. The length of the linker between domains affects the spacing of guanosine residues in oligonucleotides that are preferentially bound. These studies provide a proof of principle that NC-like CCHC zinc-binding domains can be utilized as a basis for designing peptides that bind specific single-stranded nucleic acid sequences.
C1 [Guerrerio, Anthony L.; Berg, Jeremy M.] Johns Hopkins Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Berg, Jeremy M.] NIDDK, Bethesda, MD 20892 USA.
RP Berg, JM (reprint author), Johns Hopkins Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM bergj@mail.nih.gov
OI Berg, Jeremy/0000-0003-3022-0963
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of General Medical Sciences
FX This work was supported by the intramural research program at the
National Institute of Diabetes and Digestive and Kidney Diseases and by
the National Institute of General Medical Sciences. We thank Drs.
Gregory J. Gatto, Jr., and Barbara Amann for advice and assistance.
NR 49
TC 3
Z9 3
U1 0
U2 2
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 JUL 21
PY 2010
VL 132
IS 28
BP 9638
EP 9643
DI 10.1021/ja910942v
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 628AQ
UT WOS:000280086800039
PM 20586464
ER
PT J
AU Zhang, YL
Li, QA
Rodriguez, LG
Gildersleeve, JC
AF Zhang, Yalong
Li, Qian
Rodriguez, Luis G.
Gildersleeve, Jeffrey C.
TI An Array-Based Method To Identify Multivalent Inhibitors
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID LECTIN PA-IL; PSEUDOMONAS-AERUGINOSA; CARBOHYDRATE MICROARRAY;
TN-ANTIGEN; GALACTOPHILIC LECTIN; VACCINE DEVELOPMENT; GLYCAN
MICROARRAYS; SERUM ANTIBODIES; SPECIFICITY; BINDING
AB Carbohydrate protein interactions play a critical role in a variety of biological processes, and agonists/antagonists of these interactions are useful as biological probes and therapeutic agents. Most carbohydrate-binding proteins achieve tight binding through formation of a multivalent complex. Therefore, both ligand structure and presentation contribute to recognition. Since there are many potential combinations of structure, spacing, and orientation to consider and the optimal one cannot be predicted, high-throughput approaches for analyzing carbohydrate protein interactions and designing inhibitors are appealing. In this report, we develop a strategy to vary neoglycoprotein density on a surface of a glycan array. This feature of presentation was combined with variations in glycan structure and glycan density to produce an array with approximately 600 combinations of glycan structure and presentation. The unique array platform allows one to distinguish between different types of multivalent complexes on the array surface. To illustrate the advantages of this format, it was used to rapidly identify multivalent probes for various lectins. The new array was first tested with several plant lectins, including concanavalin A (conA), Vicia villosa isolectin B4 (VVL-B(4)), and Ricinus communis agglutinin (RCA120). Next, it was used to rapidly identify potent multivalent inhibitors of Pseudomonas aeruginosa lectin I (PA-IL), a key protein involved in opportunistic infections of P. aeruginosa, and mouse macrophage galactose-type lectin (mMGL-2), a protein expressed on antigen presenting cells that may be useful as a vaccine targeting receptor. An advantage of the approach is that structural information about the lectin/receptor is not required to obtain a multivalent inhibitor/probe.
C1 [Zhang, Yalong; Li, Qian; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Rodriguez, Luis G.] NCI Frederick, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Adv Technol Program, Frederick, MD 21702 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, 376 Boyles St,Bldg 376, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
RI Gildersleeve, Jeffrey/N-3392-2014
FU NIH, NCI
FX We thank Professor Lara Mahal for the generous gift of PA-IL. We thank
the Optical Microscopy and Analysis Laboratory, SAIC-Frederick, Inc.,
Advanced Technology Program for use of the confocal microscope. This
research was supported by the Intramural Research Program of the NIH,
NCI.
NR 60
TC 47
Z9 47
U1 1
U2 15
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 JUL 21
PY 2010
VL 132
IS 28
BP 9653
EP 9662
DI 10.1021/ja100608w
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA 628AQ
UT WOS:000280086800041
PM 20583754
ER
PT J
AU Taplin, SH
Abraham, L
Geller, BM
Yankaskas, BC
Buist, DSM
Smith-Bindman, R
Lehman, C
Weaver, D
Carney, PA
Barlow, WE
AF Taplin, Stephen H.
Abraham, L.
Geller, B. M.
Yankaskas, B. C.
Buist, D. S. M.
Smith-Bindman, R.
Lehman, C.
Weaver, D.
Carney, P. A.
Barlow, W. E.
TI Effect of Previous Benign Breast Biopsy on the Interpretive Performance
of Subsequent Screening Mammography
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID UNITED-STATES; MANAGEMENT RECOMMENDATIONS; REPLACEMENT THERAPY;
INDIVIDUAL WOMEN; CANCER; SPECIFICITY; SENSITIVITY; ACCURACY;
CONCORDANCE; DISEASE
AB Most breast biopsies will be negative for cancer. Benign breast biopsy can cause changes in the breast tissue, but whether such changes affect the interpretive performance of future screening mammography is not known.
We prospectively evaluated whether self-reported benign breast biopsy was associated with reduced subsequent screening mammography performance using examination data from the mammography registries of the Breast Cancer Surveillance Consortium from January 2, 1996, through December 31, 2005. A positive interpretation was defined as a recommendation for any additional evaluation. Cancer was defined as any invasive breast cancer or ductal carcinoma in situ diagnosed within 1 year of mammography screening. Measures of mammography performance (sensitivity, specificity, and positive predictive value 1 [PPV1]) were compared both at woman level and breast level in the presence and absence of self-reported benign biopsy history. Referral to biopsy was considered a positive interpretation to calculate positive predictive value 2 (PPV2). Multivariable analysis of a correct interpretation on each performance measure was conducted after adjusting for registry, year of examination, patient characteristics, months since last mammogram, and availability of comparison film. Accuracy of the mammogram interpretation was measured using area under the receiver operating characteristic curve (AUC). All statistical tests were two-sided.
A total of 2 007 381 screening mammograms were identified among 799 613 women, of which 14.6% mammograms were associated with self-reported previous breast biopsy. Multivariable adjusted models for mammography performance showed reduced specificity (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.73 to 0.75, P < .001), PPV2 (OR = 0.85, 95% CI = 0.79 to 0.92, P < .001), and AUC (AUC 0.892 vs 0.925, P < .001) among women with self-reported benign biopsy. There was no difference in sensitivity or PPV1 in the same adjusted models, although unadjusted differences in both were found. Specificity was lowest among women with documented fine needle aspiration-the least invasive biopsy technique (OR = 0.58, 95% CI = 0.55 to 0.61, P < .001). Repeating the analysis among women with documented biopsy history, unilateral biopsy history, or restricted to invasive cancers did not change the results.
Self-reported benign breast biopsy history was associated with statistically significantly reduced mammography performance. The difference in performance was likely because of tissue characteristics rather than the biopsy itself.
C1 [Taplin, Stephen H.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Abraham, L.; Buist, D. S. M.] Grp Hlth Res Inst, Seattle, WA USA.
[Geller, B. M.] Univ Vermont, Vermont Canc Ctr, Burlington, VT USA.
[Weaver, D.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Yankaskas, B. C.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Smith-Bindman, R.] Univ Calif San Francisco, Dept Radiol, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Smith-Bindman, R.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Med, San Francisco, CA 94143 USA.
[Lehman, C.] Univ Washington, Dept Radiol & Canc Res & Biostat, Seattle, WA 98195 USA.
[Barlow, W. E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Carney, P. A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA.
[Carney, P. A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
RP Taplin, SH (reprint author), 6130 Execut Blvd,MSC 7344,EPN 4005, Rockville, MD 20852 USA.
EM taplins@mail.nih.gov
FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082,
U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]
FX This study was supported by a National Cancer Institute-funded Breast
Cancer Surveillance Consortium (BCSC) co-operative agreement (U01CA63740
K Kerlikowske, U01CA86076 D Miglioretti, U01CA86082 T Onega, U01CA63736
G Cutter, U01CA70013 B Geller, U01CA69976 R Rosenberg, U01CA63731 D
Buist, U01CA70040 B Yankaskas) and direct salary support for the first
author through the National Cancer Institute.
NR 32
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U1 1
U2 3
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 JUL 21
PY 2010
VL 102
IS 14
BP 1040
EP 1051
DI 10.1093/jnci/djq233
PG 12
WC Oncology
SC Oncology
GA 630JO
UT WOS:000280269400010
PM 20601590
ER
PT J
AU Zhao, YD
Wang, E
Liu, H
Rotunno, M
Koshiol, J
Marincola, FM
Landi, MT
McShane, LM
AF Zhao, Yingdong
Wang, Ena
Liu, Hui
Rotunno, Melissa
Koshiol, Jill
Marincola, Francesco M.
Landi, Maria Teresa
McShane, Lisa M.
TI Evaluation of normalization methods for two-2channel microRNA
microarrays
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID STEM-CELLS; CANCER; DIFFERENTIATION; ARRAY
AB Background: MiR arrays distinguish themselves from gene expression arrays by their more limited number of probes, and the shorter and less flexible sequence in probe design. Robust data processing and analysis methods tailored to the unique characteristics of miR arrays are greatly needed. Assumptions underlying commonly used normalization methods for gene expression microarrays containing tens of thousands or more probes may not hold for miR microarrays. Findings from previous studies have sometimes been inconclusive or contradictory. Further studies to determine optimal normalization methods for miR microarrays are needed.
Methods: We evaluated many different normalization methods for data generated with a custom-made two channel miR microarray using two data sets that have technical replicates from several different cell lines. The impact of each normalization method was examined on both within miR error variance (between replicate arrays) and between miR variance to determine which normalization methods minimized differences between replicate samples while preserving differences between biologically distinct miRs.
Results: Lowess normalization generally did not perform as well as the other methods, and quantile normalization based on an invariant set showed the best performance in many cases unless restricted to a very small invariant set. Global median and global mean methods performed reasonably well in both data sets and have the advantage of computational simplicity.
Conclusions: Researchers need to consider carefully which assumptions underlying the different normalization methods appear most reasonable for their experimental setting and possibly consider more than one normalization approach to determine the sensitivity of their results to normalization method used.
C1 [Rotunno, Melissa; Koshiol, Jill; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhao, Yingdong; McShane, Lisa M.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Wang, Ena; Liu, Hui; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov; McShaneL@ctep.nci.nih.gov
NR 19
TC 10
Z9 10
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 21
PY 2010
VL 8
AR 69
DI 10.1186/1479-5876-8-69
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 657WE
UT WOS:000282448800001
PM 20663154
ER
PT J
AU Druey, KM
Greipp, PR
AF Druey, Kirk M.
Greipp, Philip R.
TI Narrative Review: The Systemic Capillary Leak Syndrome
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; OF-THE-LITERATURE; CLARKSONS-DISEASE;
POEMS-SYNDROME; MONOCLONAL GAMMOPATHY; COMPARTMENT SYNDROME;
SCHNITZLERS-SYNDROME; BARRIER FUNCTION; PROINFLAMMATORY CYTOKINES;
MULTIPLE-MYELOMA
AB The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia. Its cause is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these. Fewer than 150 cases of SCLS have been reported, but the condition is probably underrecognized because of its nonspecific symptoms and signs and high mortality rate. Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis and muscle compartment syndromes, and venous thromboembolism. Shock and edema reverse almost as quickly as they begin, at which time patients are at risk for death from flash pulmonary edema during rapid fluid remobilization. Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema. Acute episodes are treated with vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, to prevent the sequelae of underperfusion. Between episodes, patients may be treated with theophylline and terbutaline, which clinical experience suggests may reduce the severity and frequency of acute episodes. Prognosis is uncertain, but patients who survive an initial severe SCLS episode are estimated to have a 10-year survival rate greater than 70%. Much remains to be learned about SCLS, and clinicians should consider the diagnosis in patients with unexplained edema, increased hematocrit, and hypotension.
C1 [Druey, Kirk M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
Mayo Clin, Coll Med, Rochester, MN USA.
RP Druey, KM (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,Room 11N242, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [AI001083 LAD]
FX Grant Support: In part by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, grant AI001083 LAD (Dr. Druey).
NR 90
TC 74
Z9 88
U1 2
U2 5
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 20
PY 2010
VL 153
IS 2
BP 90
EP W32
DI 10.7326/0003-4819-153-2-201007200-00005
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 628DU
UT WOS:000280095400004
PM 20643990
ER
PT J
AU Allred, AF
Wu, GA
Wulan, T
Fischer, KF
Holbrook, MR
Tesh, RB
Wang, D
AF Allred, Adam F.
Wu, Guang
Wulan, Tuya
Fischer, Kael F.
Holbrook, Michael R.
Tesh, Robert B.
Wang, David
TI VIPR: A probabilistic algorithm for analysis of microbial detection
microarrays
SO BMC BIOINFORMATICS
LA English
DT Article
ID PATHOGEN-DETECTION MICROARRAY; DNA MICROARRAYS; OLIGONUCLEOTIDE
MICROARRAY; IDENTIFICATION; VIRUSES; ENTEROVIRUSES; HYBRIDIZATION;
FLAVIVIRUSES; ARRAY
AB Background: All infectious disease oriented clinical diagnostic assays in use today focus on detecting the presence of a single, well defined target agent or a set of agents. In recent years, microarray-based diagnostics have been developed that greatly facilitate the highly parallel detection of multiple microbes that may be present in a given clinical specimen. While several algorithms have been described for interpretation of diagnostic microarrays, none of the existing approaches is capable of incorporating training data generated from positive control samples to improve performance.
Results: To specifically address this issue we have developed a novel interpretive algorithm, VIPR (Viral Identification using a PRobabilistic algorithm), which uses Bayesian inference to capitalize on empirical training data to optimize detection sensitivity. To illustrate this approach, we have focused on the detection of viruses that cause hemorrhagic fever (HF) using a custom HF-virus microarray. VIPR was used to analyze 110 empirical microarray hybridizations generated from 33 distinct virus species. An accuracy of 94% was achieved as measured by leave-one-out cross validation. Conclusions
VIPR outperformed previously described algorithms for this dataset. The VIPR algorithm has potential to be broadly applicable to clinical diagnostic settings, wherein positive controls are typically readily available for generation of training data.
C1 [Allred, Adam F.; Wu, Guang; Wulan, Tuya; Wang, David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Allred, Adam F.; Wu, Guang; Wulan, Tuya; Wang, David] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Fischer, Kael F.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
[Holbrook, Michael R.; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
[Holbrook, Michael R.] NIH, Integrated Res Facil, Div Clin Med, Frederick, MD 21702 USA.
RP Wang, D (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
EM davewang@borcim.wustl.edu
RI Fischer, Kael/F-7756-2015
OI Fischer, Kael/0000-0002-7547-330X
FU National Institutes of Health [U01 AI070374]
FX This work was supported by National Institutes of Health grant U01
AI070374. We would like to thank Gary Stormo, Bill Shannon, and Rob
Culverhouse for useful discussions.
NR 25
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U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 20
PY 2010
VL 11
AR 384
DI 10.1186/1471-2105-11-384
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 645GV
UT WOS:000281441400002
PM 20646301
ER
PT J
AU Goldstein, E
Cowling, BJ
O'Hagan, JJ
Danon, L
Fang, VJ
Hagy, A
Miller, JC
Reshef, D
Robins, J
Biedrzycki, P
Lipsitch, M
AF Goldstein, Edward
Cowling, Benjamin J.
O'Hagan, Justin J.
Danon, Leon
Fang, Vicky J.
Hagy, Angela
Miller, Joel C.
Reshef, David
Robins, James
Biedrzycki, Paul
Lipsitch, Marc
TI Oseltamivir for treatment and prevention of pandemic influenza A/H1N1
virus infection in households, Milwaukee, 2009
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID SERIAL INTERVAL; HOSPITALIZATION; TRANSMISSION
AB Background: During an influenza pandemic, a substantial proportion of transmission is thought to occur in households. We used data on influenza progression in individuals and their contacts collected by the City of Milwaukee Health Department (MHD) to study the transmission of pandemic influenza A/H1N1 virus in 362 households in Milwaukee, WI, and the effects of oseltamivir treatment and chemoprophylaxis.
Methods: 135 households had chronological information on symptoms and oseltamivir usage for all household members. The effect of oseltamivir treatment and other factors on the household secondary attack rate was estimated using univariate and multivariate logistic regression with households as the unit of analysis. The effect of oseltamivir treatment and other factors on the individual secondary attack rate was estimated using univariate and multivariate logistic regression with individual household contacts as the unit of analysis, and a generalized estimating equations approach was used to fit the model to allow for clustering within households.
Results: Oseltamivir index treatment on onset day or the following day (early treatment) was associated with a 42% reduction (OR: 0.58, 95% CI: 0.19, 1.73) in the odds of one or more secondary infections in a household and a 50% reduction (OR: 0.5, 95% CI: 0.17, 1.46) in the odds of a secondary infection in individual contacts. The confidence bounds are wide due to a small sample of households with early oseltamivir index usage - in 29 such households, 5 had a secondary attack. Younger household contacts were at higher risk of infection (OR: 2.79, 95% CI: 1.50-5.20).
Conclusions: Early oseltamivir treatment may be beneficial in preventing H1N1pdm influenza transmission; this may have relevance to future control measures for influenza pandemics. Larger randomized trials are needed to confirm this finding statistically.
C1 [Goldstein, Edward; O'Hagan, Justin J.; Danon, Leon; Miller, Joel C.; Robins, James; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Cowling, Benjamin J.; Fang, Vicky J.] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Danon, Leon] Univ Warwick, Inst Math, Coventry CV4 7AL, W Midlands, England.
[Danon, Leon] Univ Warwick, Dept Biol, Coventry CV4 7AL, W Midlands, England.
[Hagy, Angela; Biedrzycki, Paul] Milwaukee Hlth Dept, Milwaukee, WI USA.
[Reshef, David] Univ Oxford, Oxford, England.
[Miller, Joel C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Goldstein, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
EM egoldste@hsph.harvard.edu
RI Cowling, Benjamin/C-4263-2009; Danon, Leon/J-6324-2012; Miller,
Joel/C-4229-2015;
OI Cowling, Benjamin/0000-0002-6297-7154; Danon, Leon/0000-0002-7076-1871;
Miller, Joel/0000-0003-4426-0405; Lipsitch, Marc/0000-0003-1504-9213
FU US National Institutes of Health [5U01GM076497, 1U54GM088558]; Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX This work was funded by the US National Institutes of Health Models of
Infectious Disease Agent Study Cooperative Agreements 5U01GM076497 and
1U54GM088558 to ML for the Harvard Center for Communicable Disease
Dynamics (ML, EG, JO), and by the RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health (JCM).
NR 20
TC 23
Z9 24
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD JUL 20
PY 2010
VL 10
AR 211
DI 10.1186/1471-2334-10-211
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 666SH
UT WOS:000283138900001
PM 20642862
ER
PT J
AU Gilchrist, DA
Adelman, K
AF Gilchrist, Daniel A.
Adelman, Karen
TI moonshine Illuminates a Developmental Role for Regulated Transcription
Elongation
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID INITIATION
C1 [Gilchrist, Daniel A.; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
OI Gilchrist, Daniel/0000-0003-1668-2790
FU Intramural NIH HHS [ZIA ES101987-04]
NR 10
TC 0
Z9 0
U1 0
U2 0
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 JUL 20
PY 2010
VL 19
IS 1
BP 9
EP 10
DI 10.1016/j.devcel.2010.07.003
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 632ZP
UT WOS:000280469100005
PM 20643345
ER
PT J
AU Park, HS
Ahn, C
Fung, DT
Ren, YP
Zhang, LQ
AF Park, Hyung-Soon
Ahn, Chulhyun
Fung, David T.
Ren, Yupeng
Zhang, Li-Qun
TI A knee-specific finite element analysis of the human anterior cruciate
ligament impingement against the femoral intercondylar notch
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Anterior cruciate ligament (ACL); Noncontact ACL injury; ACL
impingement; Finite element analysis
ID ACL IMPINGEMENT; MODEL; BIOMECHANICS; INJURIES; JOINT
AB This work presents a finite element analysis of anterior cruciate ligament (ACL) impingement against the intercondylar notch during tibial external rotation and abduction, as a mechanism of noncontact ACL injuries. Experimentally, ACL impingement was measured in a cadaveric knee in terms of impingement contact pressure and six degrees-of-freedom tibiofemoral kinematics. Three-dimensional geometries of the ACL, femur and tibia were incorporated into the finite element model of the individual knee specimen. A fiber-reinforced model was adopted, which accounts for the anisotropy, large deformation, nonlinearity and incompressibility of the ACL. With boundary conditions specified based on the experimental tibiofemoral kinematics, the finite element analysis showed that impingement between the ligament and the lateral wall of intercondylar notch could occur when qthe knee at 45 degrees was externally rotated at 29.1 degrees and abducted at 10.0 degrees. Strong contact pressure and tensile stress occurred at the impinging and nonimpinging sides of the ligament, respectively. The impingement force and contact area estimated from the model matched their counterparts from the corresponding cadaver experiment. The modeling and experimental approach provides a useful tool to characterize potential ACL impingement on a knee-specific basis, which may help elucidate the ACL injury mechanism and develop more effective treatments. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Park, Hyung-Soon; Ahn, Chulhyun; Fung, David T.; Ren, Yupeng; Zhang, Li-Qun] Rehabil Inst Chicago, Chicago, IL 60611 USA.
[Zhang, Li-Qun] Northwestern Univ, Dept Orthopaed Surg, Evanston, IL 60208 USA.
[Ahn, Chulhyun; Ren, Yupeng; Zhang, Li-Qun] Northwestern Univ, Dept Phys Med & Rehabil, Evanston, IL 60208 USA.
[Fung, David T.; Zhang, Li-Qun] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA.
[Park, Hyung-Soon] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD USA.
RP Zhang, LQ (reprint author), Rehabil Inst Chicago, 345 E Super St,Room 1406, Chicago, IL 60611 USA.
EM l-zhang@northwestern.edu
RI Park, Hyung-Soon/B-3334-2010
OI Park, Hyung-Soon/0000-0003-4274-7420
FU NIH [R01-AR056050, R01-HD044295, R01-AR045634]
FX The authors acknowledge the support of the NIH including the Extramural
(R01-AR056050, R01-HD044295 and R01-AR045634) and the Intramural
(NIH/CRC) programs.
NR 30
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U1 1
U2 8
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 JUL 20
PY 2010
VL 43
IS 10
BP 2039
EP 2042
DI 10.1016/j.jbiomech.2010.03.015
PG 4
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 630YR
UT WOS:000280313300031
PM 20413123
ER
PT J
AU Raymont, V
Salazar, AM
Lipsky, R
Goldman, D
Tasick, G
Grafman, J
AF Raymont, V.
Salazar, A. M.
Lipsky, R.
Goldman, D.
Tasick, G.
Grafman, J.
TI Correlates of posttraumatic epilepsy 35 years following combat brain
injury
SO NEUROLOGY
LA English
DT Article
ID PENETRATING HEAD-INJURY; POST-TRAUMATIC EPILEPSY; MECHANICAL INJURY;
SEIZURES; SOFTWARE; GENETICS; GENES; RISK
AB Background: The Vietnam Head Injury Study (VHIS) is a prospective, longitudinal follow-up of 1,221 Vietnam War veterans with mostly penetrating head injuries (PHIs). The high prevalence (45%-53%) of posttraumatic epilepsy (PTE) in this unique cohort makes it valuable for study.
Methods: A standardized multidisciplinary neurologic, cognitive, behavioral, and brain imaging evaluation was conducted on 199 VHIS veterans plus uninjured controls, some 30 to 35 years after injury, as part of phase 3 of this study.
Results: The prevalence of seizures (87 patients, 43.7%) was similar to that found during phase 2 evaluations 20 years earlier, but 11 of 87 (12.6%) reported very late onset of PTE after phase 2 (more than 14 years after injury). Those patients were not different from patients with earlier-onset PTE in any of the measures studied. Within the phase 3 cohort, the most common seizure type last experienced was complex partial seizures (31.0%), with increasing frequency after injury. Of subjects with PTE, 88% were receiving anticonvulsants. Left parietal lobe lesions and retained ferric metal fragments were associated with PTE in a logistic regression model. Total brain volume loss predicted seizure frequency.
Conclusions: Patients with PHI carry a high risk of PTE decades after their injury, and so require long-term medical follow-up. Lesion location, lesion size, and lesion type were predictors of PTE. Neurology (R) 2010;75:224-229
C1 [Raymont, V.; Salazar, A. M.; Grafman, J.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Raymont, V.; Tasick, G.] Henry M Jackson Fdn, Natl Naval Med Ctr, Vietnam Head Injury Study, Bethesda, MD USA.
[Raymont, V.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Lipsky, R.] Inova Fairfax Hosp, Inova Hlth Syst, Dept Neurosci, Falls Church, VA USA.
[Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Grafman, Jordan
H./0000-0001-8645-4457; Lipsky, Robert/0000-0001-7753-1473
FU United States Army Medical Research and Material Command; National
Institute on Alcohol Abuse and Alcoholism intramural research program;
UD Department of Defense; US Army Medical Research and Material Command;
National Institute of Neurological Disorders and Stroke intramural
research program
FX Dr. Raymont was supported by a project grant from the United States Army
Medical Research and Material Command and administered by the Henry M.
Jackson Foundation (DAMD17-01-1-0675). Dr. Salazar is CEO and Chairman
of Oncovir, Inc., in which he owns stock; serves on the editorial board
of the Journal of Neurology Neurosurgery & Psychiatry; and may accrue
revenue on a patent re: Method for Preparation of large batches of
Poly-ICLC. Dr. Lipsky serves as a field editor for Amino Acids and on
the editorial board of CNS and Neurological Disorders-Drug Targets; may
accrue revenue on a patents re: A Missense Variant (P10L) of the
Melanopsin (OPN4) Gene in Seasonal Affective Disorder and re: Methods
for detecting nucleic acid sequence variation; was supported by the
National Institute on Alcohol Abuse and Alcoholism intramural research
program; and receives research support from the UD Department of
Defense. Dr. Goldman is supported by the National Institute on Alcohol
Abuse and Alcoholism intramural research program. Ms. Tasick was
supported by a project grant from the US Army Medical Research and
Material Command and administered by the Henry M. Jackson Foundation
(DAMD17-01-1-0675). Dr. Grafman is supported by the National Institute
of Neurological Disorders and Stroke intramural research program; and
serves as Coeditor of Cortex.
NR 40
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U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 20
PY 2010
VL 75
IS 3
BP 224
EP 229
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 628ES
UT WOS:000280097900007
PM 20644150
ER
PT J
AU Sugimoto, C
Watanabe, S
Naruse, T
Kajiwara, E
Shiino, T
Umano, N
Ueda, K
Sato, H
Ohgimoto, S
Hirsch, V
Villinger, F
Ansari, AA
Kimura, A
Miyazawa, M
Suzuki, Y
Yamamoto, N
Nagai, Y
Mori, K
AF Sugimoto, Chie
Watanabe, Satoru
Naruse, Taeko
Kajiwara, Eiji
Shiino, Teiichiro
Umano, Natsuko
Ueda, Kayoko
Sato, Hirotaka
Ohgimoto, Shinji
Hirsch, Vanessa
Villinger, Francois
Ansari, Aftab A.
Kimura, Akinori
Miyazawa, Masaaki
Suzuki, Yasuo
Yamamoto, Naoki
Nagai, Yoshiyuki
Mori, Kazuyasu
TI Protection of Macaques with Diverse MHC Genotypes against a Heterologous
SIV by Vaccination with a Deglycosylated Live-Attenuated SIV
SO PLOS ONE
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTE RESPONSES; CLASS-I;
SIVMAC239 REPLICATION; RHESUS MACAQUES; CELL RESPONSES; VIRAL LOAD;
AIDS; NEUTRALIZATION; INFECTION
AB HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc), following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a successful HIV vaccine against diverse isolates.
C1 [Sugimoto, Chie; Watanabe, Satoru; Shiino, Teiichiro; Ueda, Kayoko; Sato, Hirotaka; Yamamoto, Naoki; Mori, Kazuyasu] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan.
[Sugimoto, Chie; Watanabe, Satoru; Ueda, Kayoko; Sato, Hirotaka; Mori, Kazuyasu] Natl Inst Biomed Innovat, Tsukuba Primate Res Ctr, Tsukuba, Ibaraki, Japan.
[Sugimoto, Chie; Suzuki, Yasuo; Mori, Kazuyasu] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan.
[Naruse, Taeko; Kimura, Akinori] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pathogenesis, Div Med Sci,Chiyoda Ku, Tokyo, Japan.
[Kajiwara, Eiji; Umano, Natsuko; Miyazawa, Masaaki] Kinki Univ, Sch Med, Dept Immunol, Osaka 589, Japan.
[Ohgimoto, Shinji] Osaka City Univ, Grad Sch Med, Dept Virol, Abeno Ku, Osaka 558, Japan.
[Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Villinger, Francois; Ansari, Aftab A.; Mori, Kazuyasu] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Suzuki, Yasuo] Chubu Univ, Coll Life & Hlth Sci, Dept Biomed Sci, Aichi, Japan.
[Nagai, Yoshiyuki] RIKEN, Ctr Res Network Infect Dis, Chiyoda Ku, Tokyo, Japan.
RP Sugimoto, C (reprint author), Tulane Natl Primate Res Ctr, Div Immunol, Covington, LA USA.
EM mori@nibio.go.jp
FU Health Sciences Research Grants; Ministry of Health, Labor, and Welfare
in Japan; Ministry of Education, Culture, Sports, Science and Technology
in Japan
FX This work was supported by AIDS research grants from the Health Sciences
Research Grants, from the Ministry of Health, Labor, and Welfare in
Japan, and from the Ministry of Education, Culture, Sports, Science and
Technology in Japan. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 31
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 20
PY 2010
VL 5
IS 7
AR e11678
DI 10.1371/journal.pone.0011678
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628II
UT WOS:000280109700010
PM 20652030
ER
PT J
AU Compton, ELR
Taylor, EM
Mindell, JA
AF Compton, Emma L. R.
Taylor, Erin M.
Mindell, Joseph A.
TI The 3-4 loop of an archaeal glutamate transporter homolog experiences
ligand-induced structural changes and is essential for transport
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE conformational change; mechanism; neurotransmitter; transporters
ID DEPENDENT ASPARTATE TRANSPORTER; REENTRANT LOOP;
BACILLUS-STEAROTHERMOPHILUS; PYROCOCCUS-HORIKOSHII; EXTRACELLULAR GATE;
NA+/H+ ANTIPORTER; ESCHERICHIA-COLI; SUBSTRATE; GLT-1; BINDING
AB Glutamatergic synaptic transmission is terminated by members of the excitatory amino acid transporter (EAAT) family of proteins that remove glutamate from the synaptic cleft by transporting it into surrounding glial cells. Recent structures of a bacterial homolog suggest that major motions within the transmembrane domain translocate the substrate across the membrane. However, the events leading to this large structural rearrangement are much less clear. Two reentrant loops have been proposed to act as extracellular and intracellular gates, but whether other regions of these proteins play a role in the transport process is unknown. We hypothesized that transport-related conformational changes could change the solvent accessibilities of affected residues, as reflected in protease sensitivity or small-molecule reactivity. In the model system Glt(Ph), an archaeal EAAT homologue from Pyrococcus horikoshii, limited trypsin proteolysis experiments initially identified a site in the long extracellular loop that stretches between helices 3 and 4 that becomes protected from proteolysis in the presence of a substrate, L-aspartate, or an inhibitor, DL-TBOA in the presence of Na(+), the cotransported ion. Using a combination of site-directed cysteine-scanning mutagenesis and fluorescein-5-maleimide labeling we found that positions throughout the loop experience these ligand-induced conformational changes. By selectively cleaving the 3-4 loop (via introduced Factor Xa sites) we demonstrate that it plays a vital role in the transport process; though structurally intact, the cleaved proteins are unable to transport aspartate. These results inculcate the 3-4 loop as an important player in the transport process, a finding not predicted by any of the available crystal structures of Glt(Ph).
C1 [Compton, Emma L. R.; Taylor, Erin M.; Mindell, Joseph A.] NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mindell, JA (reprint author), NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM mindellj@ninds.nih.gov
OI Mindell, Joseph/0000-0002-6952-8247
FU NIH, NINDS
FX We thank Howard Jaffe of the NINDS Protein/Peptide Facility for
performing N-terminal protein sequencing, Candace Pfefferkorn for
undertaking pilot experiments, Patricia Curran for expert technical
support, and Kenton Swartz and Mark Mayer for critical readings of the
manuscript. We also wish to acknowledge the invaluable contributions of
the inventors of cysteine and all of its uses. This work was supported
by the Intramural Research Program of the NIH, NINDS.
NR 29
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U1 0
U2 6
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 JUL 20
PY 2010
VL 107
IS 29
BP 12840
EP 12845
DI 10.1073/pnas.1003046107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628TJ
UT WOS:000280144500026
PM 20615993
ER
PT J
AU Perez-Victoria, FJ
Abascal-Palacios, G
Tascon, I
Kajava, A
Magadan, JG
Pioro, EP
Bonifacino, JS
Hierro, A
AF Perez-Victoria, F. Javier
Abascal-Palacios, Guillermo
Tascon, Igor
Kajava, Andrey
Magadan, Javier G.
Pioro, Erik P.
Bonifacino, Juan S.
Hierro, Aitor
TI Structural basis for the wobbler mouse neurodegenerative disorder caused
by mutation in the Vps54 subunit of the GARP complex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Golgi apparatus; vesicle trafficking; protein stability; X-ray
crystallography
ID MOTOR-NEURON DISEASE; TETHERING COMPLEX; LYSOSOMAL STORAGE; CATHEPSIN-D;
EARLY ENDOSOME; SNARE TLG1P; LATE GOLGI; VESICLE; EXOCYST; MODEL
AB The multisubunit Golgi-associated retrograde protein (GARP) complex is required for tethering and fusion of endosome-derived transport vesicles to the trans-Golgi network. Mutation of leucine-967 to glutamine in the Vps54 subunit of GARP is responsible for spinal muscular atrophy in the wobbler mouse, an animal model of amyotrophic lateral sclerosis. The crystal structure at 1.7 angstrom resolution of the mouse Vps54 C-terminal fragment harboring leucine-967, in conjunction with comparative sequence analysis, reveals that Vps54 has a continuous alpha-helical bundle organization similar to that of other multisubunit tethering complexes. The structure shows that leucine-967 is buried within the alpha-helical bundle through predominantly hydrophobic interactions that are critical for domain stability and folding in vitro. Mutation of this residue to glutamine does not prevent integration of Vps54 into the GARP complex but greatly reduces the half-life and levels of the protein in vivo. Severely reduced levels of mutant Vps54 and, consequently, of the whole GARP complex underlie the phenotype of the wobbler mouse.
C1 [Perez-Victoria, F. Javier; Magadan, Javier G.; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Abascal-Palacios, Guillermo; Tascon, Igor; Hierro, Aitor] Ctr Cooperat Res Biosci BioGUNE, Struct Biol Unit, Derio 48160, Spain.
[Kajava, Andrey] Univ Montpellier, Ctr Natl Rech Sci, Ctr Rech Biochim Macromol, F-34293 Montpellier, France.
[Pioro, Erik P.] Cleveland Clin, Neurol Inst, Neuromuscular Ctr, Cleveland, OH 44195 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov; ahierro@cicbiogune.es
RI Hierro, Aitor/F-9998-2011; Castilla, Joaquin/E-6952-2012; Kajava,
Andrey/E-1107-2014;
OI Hierro, Aitor/0000-0002-7721-1581; Kajava, Andrey/0000-0002-2342-6886;
Bonifacino, Juan S./0000-0002-5673-6370
FU Carlos III Health Institute [PI081739]; National Institute of Child
Health and Human Development; Basque Government [BFI08.53]; Spanish
Ministry of Science and Innovation
FX We thank the staff of the European Synchrotron Radiation Facility
(Grenoble, France) for assistance with X-ray data collection under the
Block Allocation Group MX-924. We are very grateful to Adriana L. Rojas
for discussion and comments on the manuscript. This research was
supported by the Carlos III Health Institute Grant PI081739 (to A.H.)
and the intramural program of the National Institute of Child Health and
Human Development (to J.S.B.). G.A.-P. has been supported by fellowship
from the Basque Government (BFI08.53). A.H. is the recipient of a "Ramon
y Cajal" contract from the Spanish Ministry of Science and Innovation.
NR 41
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U2 6
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 JUL 20
PY 2010
VL 107
IS 29
BP 12860
EP 12865
DI 10.1073/pnas.1004756107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628TJ
UT WOS:000280144500030
PM 20615984
ER
PT J
AU Voortman, J
Lee, JH
Killian, JK
Suuriniemi, M
Wang, YH
Lucchi, M
Smith, WI
Meltzer, P
Wang, YS
Giaccone, G
AF Voortman, Johannes
Lee, Jih-Hsiang
Killian, Jonathan Keith
Suuriniemi, Miia
Wang, Yonghong
Lucchi, Marco
Smith, William I., Jr.
Meltzer, Paul
Wang, Yisong
Giaccone, Giuseppe
TI Array comparative genomic hybridization-based characterization of
genetic alterations in pulmonary neuroendocrine tumors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE carcinoid; cell line; gene dosage; small cell lung carcinoma; therapy
ID CELL LUNG-CANCER; CARCINOID-TUMORS; IN-VITRO; DNA; EXPRESSION;
DELETIONS; MODELS; MICROARRAYS; IMBALANCES; INHIBITOR
AB The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.
C1 [Voortman, Johannes; Lee, Jih-Hsiang; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Meltzer, Paul] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lucchi, Marco] Univ Pisa, Cardiac & Thorac Dept, Div Thorac Surg, I-56120 Pisa, Italy.
[Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; LUCCHI,
MARCO/0000-0001-9909-6820
NR 48
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U1 1
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 20
PY 2010
VL 107
IS 29
BP 13040
EP 13045
DI 10.1073/pnas.1008132107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628TJ
UT WOS:000280144500061
PM 20615970
ER
PT J
AU Wong, WPS
Tiano, JP
Liu, SH
Hewitt, SC
May, C
Dalle, S
Katzenellenbogen, JA
Katzenellenbogen, BS
Korach, KS
Mauvais-Jarvis, F
AF Wong, Winifred P. S.
Tiano, Joseph P.
Liu, Suhuan
Hewitt, Sylvia C.
Le May, Cedric
Dalle, Stephane
Katzenellenbogen, John A.
Katzenellenbogen, Benita S.
Korach, Kenneth S.
Mauvais-Jarvis, Franck
TI Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the
insulin promoter and favors insulin synthesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diabetes; islet
ID PANCREATIC BETA-CELLS; DIABETES-MELLITUS; GENE-EXPRESSION;
MESSENGER-RNA; IN-VIVO; GLUCOSE; TRANSCRIPTION; RAT; PREGNANCY; ISLETS
AB Estrogen receptors (ERs) protect pancreatic islet survival in mice through rapid extranuclear actions. ER alpha also enhances insulin synthesis in cultured islets. Whether ERa stimulates insulin synthesis in vivo and, if so, through which mechanism(s) remain largely unknown. To address these issues, we generated a pancreas-specific ERa knockout mouse (PER alpha KO(-/-)) using the Cre-loxP strategy and used a combination of genetic and pharmacologic tools in cultured islets and beta cells. Whereas 17 beta-estradiol (E2) treatment up-regulates pancreatic insulin gene and protein content in control ER alpha lox/lox mice, these E2 effects are abolished in PER alpha KO(-/-) mice. We find that E2-activated ER alpha increases insulin synthesis by enhancing glucose stimulation of the insulin promoter activity. Using a knock-in mouse with a mutated ER alpha eliminating binding to the estrogen response elements (EREs), we show that E2 stimulation of insulin synthesis is independent of the ERE. We find that the extranuclear ER alpha interacts with the tyrosine kinase Src, which activates extracellular signal-regulated kinases(1/2), to increase nuclear localization and binding to the insulin promoter of the transcription factor NeuroD1. This study supports the importance of ERa in beta cells as a regulator of insulin synthesis in vivo.
C1 [Wong, Winifred P. S.; Tiano, Joseph P.; Liu, Suhuan; Le May, Cedric; Mauvais-Jarvis, Franck] Northwestern Univ, Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Liu, Suhuan; Mauvais-Jarvis, Franck] Northwestern Univ, Sch Med, Dept Med, Comprehens Ctr Obes, Chicago, IL 60611 USA.
[Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Dalle, Stephane] Inst Genom Fonct, Inst Natl Sante & Rech Med, U661, F-34094 Montpellier, France.
[Katzenellenbogen, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
[Katzenellenbogen, Benita S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
RP Mauvais-Jarvis, F (reprint author), Northwestern Univ, Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
EM f-mauvais-jarvis@northwestern.edu
RI Le May, cedric/D-2691-2009;
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health (NIH) [RO1 DK074970, P50 HD044405, R37
DK15556, CA18119]; Juvenile Diabetes Research Foundation [1-2006-837];
March of Dimes Birth Defects Foundation [6-FY07-312]; National Institute
of Environmental Health Sciences [Z01ES70065]; Juvenile Diabetes
Research Foundation; Endocrinology Training Grant [T32 DK007169]
FX We thank Surabhi Bhatt for technical assistance. This reseach was
supported by grants from the National Institutes of Health (NIH; RO1
DK074970, P50 HD044405), the Juvenile Diabetes Research Foundation
(1-2006-837), and the March of Dimes Birth Defects Foundation
(6-FY07-312) (to F.M.J.). The synthesis and characterization of PPT and
EDC were funded by NIH Grants R37 DK15556 (to J.A.K.) and CA18119 (to
B.S.K.). The generation of the ERalox/lox mice was funded by the
National Institute of Environmental Health Sciences, Division of
Intramural Research Grant Z01ES70065 (to K.S.K.). C.L.M. was the
recipient of a Juvenile Diabetes Research Foundation postdoctoral
fellowship, and J.T. was a trainee funded by Endocrinology Training
Grant T32 DK007169.
NR 31
TC 56
Z9 59
U1 0
U2 6
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 JUL 20
PY 2010
VL 107
IS 29
BP 13057
EP 13062
DI 10.1073/pnas.0914501107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628TJ
UT WOS:000280144500064
PM 20616010
ER
PT J
AU Monosov, IE
Sheinberg, DL
Thompson, KG
AF Monosov, Ilya E.
Sheinberg, David L.
Thompson, Kirk G.
TI Paired neuron recordings in the prefrontal and inferotemporal cortices
reveal that spatial selection precedes object identification during
visual search
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE attention; cognition; object recognition; perception
ID INFERIOR TEMPORAL CORTEX; FRONTAL EYE FIELD; NATURAL SCENES; ATTENTION;
RECOGNITION; PERCEPTION; INTERFERENCE; MONKEY; LOCUS; AREAS
AB We addressed the question of how we locate and identify objects in complex natural environments by simultaneously recording single neurons from two brain regions that play different roles in this familiar activity-the frontal eye field (FEF), an area in the prefrontal cortex that is involved in visual spatial selection, and the inferotemporal cortex (IT), which is involved in object recognition-in monkeys performing a covert visual search task. Although the monkeys reported object identity, not location, neural activity specifying target location was evident in FEF before neural activity specifying target identity in IT. These two distinct processes were temporally correlated implying a functional linkage between the end stages of "where" and "what" visual processing and indicating that spatial selection is necessary for the formation of complex object representations associated with visual perception.
C1 [Monosov, Ilya E.; Thompson, Kirk G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Sheinberg, David L.] Brown Univ, Dept Neurosci, Providence, RI 02906 USA.
RP Monosov, IE (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM ilya.monosov@gmail.com
FU National Eye Institute, National Institutes of Health
FX We thank Drs. Ethan S. Bromberg-Martin, Bruce G. Cumming, Okihide
Hikosaka, Masaharu Yasuda, Robert H. Wurtz, and Jeffrey D. Schall for
helpful discussion and M. K. Smith, G. Tansey, D. Parker, B. Nagy, and
J. W. McClurkin for technical assistance. This work was supported by the
intramural research program at the National Eye Institute, National
Institutes of Health.
NR 40
TC 19
Z9 19
U1 3
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 JUL 20
PY 2010
VL 107
IS 29
BP 13105
EP 13110
DI 10.1073/pnas.1002870107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628TJ
UT WOS:000280144500072
PM 20615946
ER
PT J
AU Gorospe, M
Srikantan, S
Abdelmohsen, K
Marasa, BS
AF Gorospe, Myriam
Srikantan, Subramanya
Abdelmohsen, Kotb
Marasa, Bernard S.
TI Response to Comment on "Increased MKK4 Abundance with Replicative
Senescence Is Linked to the Joint Reduction of Multiple MicroRNAs"
SO SCIENCE SIGNALING
LA English
DT Letter
ID TUMOR SUPPRESSION; PROTEIN-KINASE; PRAK
AB Moens and colleagues express concern that our report of phosphorylation of p38-regulated/activated protein kinase (PRAK) at Ser93 in senescent cells may be incorrect as a result of their inability to detect phosphorylated PRAK with the same antibody. We provide additional characterization of the antibody that we used and show that there is a 42-kilodalton phosphoprotein detected by this antibody, but that this phosphoprotein may not be PRAK.
C1 [Gorospe, Myriam; Srikantan, Subramanya; Abdelmohsen, Kotb; Marasa, Bernard S.] NIA, Lab Cellular & Mol Biol, IRP, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, Lab Cellular & Mol Biol, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen,
Kotb/0000-0001-6240-5810
NR 6
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD JUL 20
PY 2010
VL 3
IS 131
AR lc2
DI 10.1126/scisignal.3131lc2
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 628NI
UT WOS:000280126700002
ER
PT J
AU Kubler-Kielb, J
Vinogradov, E
Mocca, C
Pozsgay, V
Coxon, B
Robbins, JB
Schneerson, R
AF Kubler-Kielb, Joanna
Vinogradov, Evgeny
Mocca, Christopher
Pozsgay, Vince
Coxon, Bruce
Robbins, John B.
Schneerson, Rachel
TI Immunochemical studies of Shigella flexneri 2a and 6, and Shigella
dysenteriae type 1 O-specific polysaccharide-core fragments and their
protein conjugates as vaccine candidates
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Shigella; LPS; Vaccine; Conjugate
ID ESCHERICHIA-COLI; LIPOPOLYSACCHARIDE; IMMUNOGENICITY; GLUCOSYLATION;
ACETYLATION; ANTIBODIES; ANTIGENS; EFFICACY; REGION; MICE
AB There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of a Shigella vaccines is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates. This finding is now extended to the O-SPC of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1. The structures of O-SPC, containing core plus 1-4 O-SP repeat units (RUs), were analyzed by NMR and mass spectroscopy. The first RUs attached to the cores of S. flexneri 2a and 6 LPS were different from the following RUs in their O-acetylation and/or glucosylation. Conjugates of core plus more than 1 RU were necessary to induce LPS antibodies in mice. The resulting antibody levels were comparable to those induced by the full length O-SP conjugates. In S. dysenteriae type 1, the first RU was identical to the following RUs, with the exception that the GIcNAc was bound to the core in the beta-configuration, while in all other RUs the GIcNAc was present in the a-configuration. In spite of this difference, conjugates of S. dysenteriae type 1 core with 1, 2, or 3 RUs induced LPS antibodies in mice with levels statistically higher than those of the full size O-SP conjugates. O-SPC conjugates are easy to prepare, characterize, and standardize, and their clinical evaluation is planned. Published by Elsevier Ltd.
C1 [Kubler-Kielb, Joanna; Mocca, Christopher; Pozsgay, Vince; Coxon, Bruce; Robbins, John B.; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Vinogradov, Evgeny] CNR, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada.
RP Kubler-Kielb, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kielbj@mail.nih.gov
OI Vinogradov, Evgeny/0000-0002-5364-1376
FU NIH, NICHD
FX This research was supported by the Intramural Research Program of the
NIH, NICHD. The authors thank Chunyan Guo for technical assistance.
NR 28
TC 17
Z9 19
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD JUL 19
PY 2010
VL 345
IS 11
BP 1600
EP 1608
DI 10.1016/j.carres.2010.05.006
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 631WA
UT WOS:000280380100013
PM 20542498
ER
PT J
AU Stern, MD
AF Stern, Michael D.
TI Patrimony and the Evolution of Risk-Taking
SO PLOS ONE
LA English
DT Article
ID GAMBLING BEHAVIOR; PREFERENCES; PSYCHOLOGY; TASK
AB The propensity to make risky choices has a genetic component, and recent studies have identified several specific genes that contribute to this trait. Since risk-taking often appears irrational or maladaptive, the question arises how (or if) natural selection favors risk-taking. Here we show, using a stochastic simulation of selection between two hypothetical species, "R'' (risk-seeking) and "A'' (risk-averse) that, when expected reproductive fitness of the individual is unaffected by the making of the risky choice (winnings balanced by losses) natural selection (taken to the point of extinction) favors the risk-averse species. However, the situation is entirely reversed if offspring are permitted to inherit a small fraction of the parent's increased or decreased fitness acquired through risk-taking. This seemingly Lamarckian form of inheritance actually corresponds to the human situation when property or culture are transmitted in families. In the presence of this "cultural inheritance'', the long-shot risk-taking species was overwhelmingly favored, even when 90% of individuals were rendered sterile by a losing choice. Given this strong effect in a minimal model, it is important to consider the co-evolution of genes and culture when interpreting the genetics of risk-taking. This conclusion applies, in principle, to any species where parental resources can directly affect the fecundity of offspring. It might also be relevant to the effects of epigenetic inheritance, if the epigenetic state of zygotes can be affected by parental experiences.
C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
RP Stern, MD (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
EM sternm@grc.nia.nih.gov
FU National Institute on Aging of the National Institutes of Health
FX This work was entirely supported by the Intramual Research Program of
the National Institute on Aging of the 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 27
TC 4
Z9 4
U1 0
U2 12
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 JUL 19
PY 2010
VL 5
IS 7
AR e11656
DI 10.1371/journal.pone.0011656
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 627TK
UT WOS:000280065600018
PM 20668653
ER
PT J
AU Wang, TJ
Zhang, F
Richards, JB
Kestenbaum, B
van Meurs, JB
Berry, D
Kiel, DP
Streeten, EA
Ohlsson, C
Koller, DL
Peltonen, L
Cooper, JD
O'Reilly, PF
Houston, DK
Glazer, NL
Vandenput, L
Peacock, M
Shi, J
Rivadeneira, F
McCarthy, MI
Anneli, P
de Boer, IH
Mangino, M
Kato, B
Smyth, DJ
Booth, SL
Jacques, PF
Burke, GL
Goodarzi, M
Cheung, CL
Wolf, M
Rice, K
Goltzman, D
Hidiroglou, N
Ladouceur, M
Wareham, NJ
Hocking, LJ
Hart, D
Arden, NK
Cooper, C
Malik, S
Fraser, WD
Hartikainen, AL
Zhai, GJ
Macdonald, HM
Forouhi, NG
Loos, RJF
Reid, DM
Hakim, A
Dennison, E
Liu, YM
Power, C
Stevens, HE
Jaana, L
Vasan, RS
Soranzo, N
Bojunga, J
Psaty, BM
Lorentzon, M
Foroud, T
Harris, TB
Hofman, A
Jonsson, JO
Cauley, JA
Uitterlinden, AG
Gibson, Q
Jarvelin, MR
Karasik, D
Siscovick, DS
Econs, MJ
Kritchevsky, SB
Florez, JC
Todd, JA
Dupuis, J
Hypponen, E
Spector, TD
AF Wang, Thomas J.
Zhang, Feng
Richards, J. Brent
Kestenbaum, Bryan
van Meurs, Joyce B.
Berry, Diane
Kiel, Douglas P.
Streeten, Elizabeth A.
Ohlsson, Claes
Koller, Daniel L.
Peltonen, Leena
Cooper, Jason D.
O'Reilly, Paul F.
Houston, Denise K.
Glazer, Nicole L.
Vandenput, Liesbeth
Peacock, Munro
Shi, Julia
Rivadeneira, Fernando
McCarthy, Mark I.
Anneli, Pouta
de Boer, Ian H.
Mangino, Massimo
Kato, Bernet
Smyth, Deborah J.
Booth, Sarah L.
Jacques, Paul F.
Burke, Greg L.
Goodarzi, Mark
Cheung, Ching-Lung
Wolf, Myles
Rice, Kenneth
Goltzman, David
Hidiroglou, Nick
Ladouceur, Martin
Wareham, Nicholas J.
Hocking, Lynne J.
Hart, Deborah
Arden, Nigel K.
Cooper, Cyrus
Malik, Suneil
Fraser, William D.
Hartikainen, Anna-Liisa
Zhai, Guangju
Macdonald, Helen M.
Forouhi, Nita G.
Loos, Ruth J. F.
Reid, David M.
Hakim, Alan
Dennison, Elaine
Liu, Yongmei
Power, Chris
Stevens, Helen E.
Jaana, Laitinen
Vasan, Ramachandran S.
Soranzo, Nicole
Bojunga, Joerg
Psaty, Bruce M.
Lorentzon, Mattias
Foroud, Tatiana
Harris, Tamara B.
Hofman, Albert
Jonsson, John-Olov
Cauley, Jane A.
Uitterlinden, Andre G.
Gibson, Quince
Jarvelin, Marjo-Riitta
Karasik, David
Siscovick, David S.
Econs, Michael J.
Kritchevsky, Stephen B.
Florez, Jose C.
Todd, John A.
Dupuis, Josee
Hyppoenen, Elina
Spector, Timothy D.
TI Common genetic determinants of vitamin D insufficiency: a genome-wide
association study
SO LANCET
LA English
DT Article
ID D-BINDING PROTEIN; RANDOMIZED CONTROLLED-TRIALS; LEMLI-OPITZ-SYNDROME; D
DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; PLASMA-CONCENTRATIONS; D
SUPPLEMENTATION; CANCER RISK; METAANALYSIS; CALCIUM
AB Background Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.
Methods We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants.
Findings Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-22) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2-16, p=1.0x10(-26)) compared with those in the lowest quartile.
Interpretation Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency.
C1 [Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kiel, Douglas P.; Cheung, Ching-Lung; Karasik, David] Hebrew SeniorLife, Inst Aging Res, Genet Epidemiol Program, Boston, MA USA.
[Wang, Thomas J.; Florez, Jose C.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Thomas J.; Kiel, Douglas P.; Vasan, Ramachandran S.; Dupuis, Josee] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Zhang, Feng; Mangino, Massimo; Kato, Bernet; Hart, Deborah; Zhai, Guangju; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Richards, J. Brent; Ladouceur, Martin] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Goltzman, David] McGill Univ, Ctr Hlth, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent; Goltzman, David; Ladouceur, Martin] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent; Ladouceur, Martin] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent; Ladouceur, Martin] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ H3T 1E2, Canada.
[Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Harborview Med Ctr, Kidney Res Inst, Div Nephrol, Seattle, WA 98104 USA.
[Glazer, Nicole L.; Rice, Kenneth; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98104 USA.
[Glazer, Nicole L.; Rice, Kenneth; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.
[Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA.
[van Meurs, Joyce B.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Gibson, Quince] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Klin Genet, Rotterdam, Netherlands.
[van Meurs, Joyce B.; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] NGI, Sponsored NCHA, Rotterdam, Netherlands.
[Berry, Diane; Power, Chris; Hyppoenen, Elina] UCL, Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, London, England.
[Berry, Diane; Power, Chris; Hyppoenen, Elina] Ctr Paediat Epidemiol & Biostat, London, England.
[Streeten, Elizabeth A.; Shi, Julia] Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA.
[Ohlsson, Claes; Vandenput, Liesbeth; Lorentzon, Mattias] Univ Gothenburg, Inst Med, Dept Internal Med, Sahlgrenska Acad, Gothenburg, Sweden.
[Jonsson, John-Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden.
[Koller, Daniel L.; Peacock, Munro; Foroud, Tatiana; Econs, Michael J.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Peltonen, Leena; Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England.
[Peltonen, Leena] Univ Helsinki, Helsinki, Finland.
[Peltonen, Leena] Inst Mol Med Finland, Natl Inst Hlth & Welf, Helsinki, Finland.
[Cooper, Jason D.; Smyth, Deborah J.; Stevens, Helen E.; Todd, John A.] Univ Cambridge, JDRF WT Diabet & Inflammat Lab, Cambridge, England.
[O'Reilly, Paul F.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, Fac Med, London, England.
[Houston, Denise K.; Liu, Yongmei; Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
[Burke, Greg L.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[McCarthy, Mark I.] Univ Oxford, OCDEM, Oxford, England.
[McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Arden, Nigel K.; Cooper, Cyrus] Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Oxford, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
[Anneli, Pouta; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer USDA, Boston, MA 02111 USA.
[Goodarzi, Mark] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
[Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA.
[Cheung, Ching-Lung] ASTAR, Genome Inst Singapore Computat & Math Biol, Singapore, Singapore.
[Hidiroglou, Nick] Hlth Canada, Ottawa, ON K1A 0L2, Canada.
[Wareham, Nicholas J.; Forouhi, Nita G.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Hocking, Lynne J.; Macdonald, Helen M.; Reid, David M.] Univ Aberdeen, Div Appl Med, Bone & Musculoskeletal Res Programme, Aberdeen, Scotland.
[Arden, Nigel K.; Cooper, Cyrus; Dennison, Elaine] Univ Southampton, MRC Epidemiol Resource Ctr, Southampton, Hants, England.
[Malik, Suneil] Publ Hlth Agcy Canada, Off Biotechnol Genom & Populat Hlth, Toronto, ON, Canada.
[Fraser, William D.] Univ Liverpool, Unit Clin Chem, Sch Clin Sci, Liverpool L69 3BX, Merseyside, England.
[Hartikainen, Anna-Liisa] Univ Oulu, Dept Obstet & Gynaecol, Oulu, Finland.
[Jaana, Laitinen; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Hakim, Alan] Whipps Cross Univ Hosp, Dept Rheumatol, London, England.
[Jaana, Laitinen] Finnish Inst Occupat Hlth, Oulu, Finland.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Bojunga, Joerg] Klinikum Johann Wolfgang Goethe Univ, Frankfurt, Germany.
[Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
RP Spector, TD (reprint author), Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Hosp Campus,1st Floor S Wing Block 4,We, London SE1 7EH, England.
EM tjwang@partners.org; e.hypponen@ich.ucl.ac.uk; tim.spector@kcl.ac.uk
RI CHEUNG, Ching-Lung/C-2529-2012; Spector, Tim/F-6533-2012; Rice,
Kenneth/A-4150-2013; Hypponen, Elina/B-2596-2014; Rivadeneira,
Fernando/O-5385-2015; Osborne, Nicholas/N-4915-2015; mangino,
massimo/F-5134-2011;
OI Dupuis, Josee/0000-0003-2871-3603; Kritchevsky,
Stephen/0000-0003-3336-6781; Kiel, Douglas/0000-0001-8474-0310; Karasik,
David/0000-0002-8826-0530; Forouhi, Nita/0000-0002-5041-248X; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Vandenput,
Liesbeth/0000-0002-1712-6131; Cauley, Jane A/0000-0003-0752-4408;
Cheung, Ching Lung/0000-0002-6233-9144; Ramachandran,
Vasan/0000-0001-7357-5970; Rice, Kenneth/0000-0001-5779-4495; Hypponen,
Elina/0000-0003-3670-9399; Rivadeneira, Fernando/0000-0001-9435-9441;
Osborne, Nicholas/0000-0002-6700-2284; mangino,
massimo/0000-0002-2167-7470; Soranzo, Nicole/0000-0003-1095-3852; smyth,
deborah/0000-0002-6330-2669; Hocking, Lynne J/0000-0002-2414-2826
FU Novartis; Roche; Amgen; NIH/NHLBI [N01-HC-25195]; American Heart
Association; US Department of Agriculture, Agricultural Research Service
[58-1950-7-707]; National Institute of Aging [AG14759]; National
Institute of Arthritis, Musculoskeletal, and Skin Diseases; National
Institute on Aging [R01 AR/AG 41398]; Affymetrix Inc [N02-HL-6-4278];
Robert Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center; Wellcome Trust;
Arthritis Research Campaign; European Community [FP7/2007-2013,
HEALTH-F2-2008-201865-GEFOS, 200800, OA /(FP7/2007-2013),
HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; UK Department of Health via
the National Institute for Health Research (NIHR) comprehensive
Biomedical Research Centre; Biotechnology and Biological Sciences
Research Council [G20234]; National Eye Institute (NEI) via an
NIH/Center for Inherited Disease Research (CIDR); Netherlands
Organization of Scientific Research (NWO) [175.010.2005.011,
911-03-012]; Research Institute for Diseases in the Elderly [014-93-015:
RIDE2]; Netherlands Genomics Initiative/NWO [050-060-810]; European
Commission [HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2008-00-TREAT-OA];
Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands
Organization for the Health Research and Development; Research Institute
for Diseases in the Elderly; Ministry of Education, Culture and Science;
Ministry for Health, Welfare and Sports; European Commission;
Municipality of Rotterdam
FX TJW has served on the scientific advisory board of Diasorin. DKH has
received honoraria from Abbott Nutrition. MW has received consultancy
fees, honoraria, and speakers' fees from Abbott and Genzyme. DMR has
acted as a consultant for Novartis, Roche, Pfizer, Amgen, Shire, Merck,
and Servier, has received speakers' fees from Novartis, Roche, and
Amgen, and owns stock in GlaxoSmithKline and Astra Zeneca. ML(2) has
received lecture fees from Novartis and Sanofi-Aventis. All other
authors declare that they have no conflicts of interest.; Framingham
Heart Study The Framingham Heart Study of the National Heart, Lung and
Blood Institute (NHLBI) of the US National Institutes of Health (NIH)
and Boston University School of Medicine is supported by the NIH/NHLBI
contract N01-HC-25195. The present study received support from the
American Heart Association, the US Department of Agriculture,
Agricultural Research Service (under Cooperative Agreement No
58-1950-7-707), and the National Institute of Aging (AG14759). DK was
supported by a grant from the National Institute of Arthritis,
Musculoskeletal, and Skin Diseases and the National Institute on Aging
(R01 AR/AG 41398). The analyses reflect intellectual input and resource
development from the Framingham Heart Study investigators participating
in the SNP Health Association Resource project. This work was partly
supported by a contract with Affymetrix Inc for genotyping services
(Contract No N02-HL-6-4278). A portion of this research used the Linux
Cluster for Genetic Analysis, which is funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. Twins UK and Chingford The study was
funded by the Wellcome Trust, Arthritis Research Campaign, European
Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement
HEALTH-F2-2008-201865-GEFOS and Seventh Framework Programme grant 200800
Treat OA /(FP7/2007-2013), ENGAGE project grant agreement
HEALTH-F4-2007-201413, and the FP.5 GenomEUtwin Project
(QLG2-CT-2002-01254). The study also receives support from the UK
Department of Health via the National Institute for Health Research
(NIHR) comprehensive Biomedical Research Centre award to Guy's & St
Thomas' NHS Foundation Trust in partnership with King's College London.
TDS is an NIHR senior investigator. The project also received support
from a Biotechnology and Biological Sciences Research Council project
grant. (G20234). The authors acknowledge the funding and support of the
National Eye Institute (NEI) via an NIH/Center for Inherited Disease
Research (CIDR) genotyping project. We thank the staff from the
Genotyping Facilities at the Wellcome Trust Sanger Institute for sample
preparation, quality control, and genotyping; Le Centre National de
Genotypage, France, for genotyping; Duke University, NC, USA, for
genotyping; and the Finnish Institute of Molecular Medicine, Finnish
Genome Center, University of Helsinki. Genotyping was also done by CIDR
as part of an NEI/NIH project grant. The Rotterdam Study This study was
funded by the Netherlands Organization of Scientific Research (NWO)
Investments (175.010.2005.011, 911-03-012), the Research Institute for
Diseases in the Elderly (014-93-015: RIDE2), the Netherlands Genomics
Initiative/NWO project 050-060-810, and the European Commission
(HEALTH-F2-2008-201865-GEFOS, and HEALTH-F2-2008-00-TREAT-OA). The
Rotterdam Study is funded by Erasmus Medical Center and Erasmus
University, Rotterdam, Netherlands Organization for the Health Research
and Development, the Research Institute for Diseases in the Elderly, the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam. We thank the staff from the Rotterdam Study,
and the participating general practitioners and pharmacists.
NR 34
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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 JUL 17
PY 2010
VL 376
IS 9736
BP 180
EP 188
DI 10.1016/S0140-6736(10)60588-0
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 630YP
UT WOS:000280313100025
PM 20541252
ER
PT J
AU Amaral, AFS
Rothman, N
Kogevinas, M
Calle, M
Guey, LT
Garcia-Closas, M
Silverman, DT
Chanock, S
Real, FX
Malats, N
AF Amaral, A. F. S.
Rothman, N.
Kogevinas, M.
Calle, M.
Guey, L. T.
Garcia-Closas, M.
Silverman, D. T.
Chanock, S.
Real, F. X.
Malats, N.
TI Selenoproteins and bladder cancer risk: A case-control study
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Amaral, A. F. S.; Guey, L. T.; Real, F. X.; Malats, N.] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
[Rothman, N.; Garcia-Closas, M.; Silverman, D. T.; Chanock, S.] NCI, Bethesda, MD 20892 USA.
[Kogevinas, M.] Municipal Inst Med Res, Barcelona, Spain.
[Calle, M.] Univ Vic, Victoria, BC, Canada.
RI Calle, M.Luz/D-2704-2015; Kogevinas, Manolis/C-3918-2017; Amaral,
Andre/A-7662-2008
OI Calle, M.Luz/0000-0001-9334-415X; Amaral, Andre/0000-0002-0369-9449
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUL 17
PY 2010
VL 196
SU S
BP S52
EP S52
DI 10.1016/j.toxlet.2010.03.207
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471300157
ER
PT J
AU Germolec, D
AF Germolec, D.
TI Evidence for the immunotoxicity of perfluorinated compounds
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Germolec, D.] NIEHS, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
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 JUL 17
PY 2010
VL 196
SU S
BP S30
EP S30
DI 10.1016/j.toxlet.2010.03.137
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471300093
ER
PT J
AU Kapetanovic, IM
Muzzio, M
Mccormick, DL
Mohammed, A
Rao, CV
Kopelovich, L
AF Kapetanovic, I. M.
Muzzio, M.
Mccormick, D. L.
Mohammed, A.
Rao, C. V.
Kopelovich, L.
TI Biodisposition of CP31398 in rat toxicology and efficacy studies
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Kapetanovic, I. M.; Kopelovich, L.] NCI, NIH, Bethesda, MD 20892 USA.
[Muzzio, M.; Mccormick, D. L.] IIT Res Inst, Chicago, IL USA.
[Mohammed, A.; Rao, C. V.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 JUL 17
PY 2010
VL 196
SU S
BP S106
EP S106
DI 10.1016/j.toxlet.2010.03.377
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471300322
ER
PT J
AU Ramdhan, DH
Kamijima, M
Wang, D
Ito, Y
Yanagiba, Y
Hayashi, Y
Naito, H
Gonzalez, FJ
Nakajima, T
AF Ramdhan, D. H.
Kamijima, M.
Wang, D.
Ito, Y.
Yanagiba, Y.
Hayashi, Y.
Naito, H.
Gonzalez, F. J.
Nakajima, T.
TI Differential response to trichloroethylene-induced hepatosteatosis in
wild-type and PPAR alpha-humanized mice
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Ramdhan, D. H.; Wang, D.; Yanagiba, Y.; Hayashi, Y.; Naito, H.; Nakajima, T.] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan.
[Kamijima, M.; Ito, Y.] Nagoya City Univ, Grad Sch Med, Nagoya, Aichi, Japan.
[Gonzalez, F. J.] NCI, US NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUL 17
PY 2010
VL 196
SU S
BP S210
EP S210
DI 10.1016/j.toxlet.2010.03.709
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471301181
ER
PT J
AU Shah, YM
Gonzalez, FJ
AF Shah, Y. M.
Gonzalez, F. J.
TI The role of miRNAs in PPARalpha induced hepatocellular carcinomas
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Shah, Y. M.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Gonzalez, F. J.] Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUL 17
PY 2010
VL 196
SU S
BP S28
EP S28
DI 10.1016/j.toxlet.2010.03.127
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471300085
ER
PT J
AU Sinha, R
Ferrucci, L
Cross, AJ
AF Sinha, R.
Ferrucci, L.
Cross, A. J.
TI Red and processed meat intake and risk of colorectal adenoma and
carcinoma from a molecular epidemiological point of view
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
C1 [Sinha, R.; Ferrucci, L.; Cross, A. J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
NR 0
TC 0
Z9 0
U1 0
U2 3
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 JUL 17
PY 2010
VL 196
SU S
BP S5
EP S5
DI 10.1016/j.toxlet.2010.03.039
PG 1
WC Toxicology
SC Toxicology
GA V25II
UT WOS:000208471300016
ER
PT J
AU Han, SJ
Makareeva, E
Kuznetsova, NV
DeRidder, AM
Sutter, MB
Losert, W
Phillips, CL
Visse, R
Nagase, H
Leikin, S
AF Han, Sejin
Makareeva, Elena
Kuznetsova, Natalia V.
DeRidder, Angela M.
Sutter, Mary Beth
Losert, Wolfgang
Phillips, Charlotte L.
Visse, Robert
Nagase, Hideaki
Leikin, Sergey
TI Molecular Mechanism of Type I Collagen Homotrimer Resistance to
Mammalian Collagenases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRIPLE-HELICAL COLLAGEN; PEPTIDE-BOND HYDROLYSIS;
EHLERS-DANLOS-SYNDROME; C-TERMINAL DOMAIN; OSTEOGENESIS IMPERFECTA;
FIBROBLAST COLLAGENASE; EXTRACELLULAR-MATRIX; ALPHA-2(I) CHAIN;
OSTEO-SARCOMA; GELATINASE-A
AB Type I collagen cleavage is crucial for tissue remodeling, but its homotrimeric isoform is resistant to all collagenases. The homotrimers occur in fetal tissues, fibrosis, and cancer, where their collagenase resistance may play an important physiological role. To understand the mechanism of this resistance, we studied interactions of alpha 1(I)(3) homotrimers and normal alpha 1(I)(2)alpha 2(I) heterotrimers with fibroblast collagenase (MMP-1). Similar MMP-1 binding to the two isoforms and similar cleavage efficiency of unwound alpha 1(I) and alpha 2(I) chains suggested increased stability and less efficient unwinding of the homotrimer triple helix at the collagenase cleavage site. The unwinding, necessary for placing individual chains inside the catalytic cleft of the enzyme, was the rate-limiting cleavage step for both collagen isoforms. Comparative analysis of the homo-and heterotrimer cleavage kinetics revealed that MMP-1 binding promotes stochastic helix unwinding, resolving the controversy between different models of collagenase action.
C1 [Han, Sejin; Makareeva, Elena; Kuznetsova, Natalia V.; DeRidder, Angela M.; Sutter, Mary Beth; Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Han, Sejin; Losert, Wolfgang] Univ Maryland, Inst Phys Sci & Technol, Dept Phys, College Pk, MD 20742 USA.
[Han, Sejin; Losert, Wolfgang] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA.
[Phillips, Charlotte L.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA.
[Visse, Robert; Nagase, Hideaki] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Div Rheumatol, London W6 8LH, England.
RP Leikin, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 9,Rm 1E-127, Bethesda, MD 20892 USA.
EM leikins@mail.nih.gov
RI Makareeva, Elena/F-5183-2011; Leikin, Sergey/A-5518-2008;
OI Leikin, Sergey/0000-0001-7095-0739; Phillips,
Charlotte/0000-0002-7761-3783
FU National Institutes of Health NICHD; NIDDK [DK069522]; National Science
Foundation [PHY-0750371]; Wellcome Trust [075473]
FX This work was supported, in whole or in part, by National Institutes of
Health NICHD Intramural Research Program grant (to S.L.) and NIDDK Grant
DK069522 (to C.L.P.). This work was also supported by National Science
Foundation Grant PHY-0750371 (to W.L.) and Wellcome Trust Program Grant
075473 (to H.N.).
NR 48
TC 48
Z9 50
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 16
PY 2010
VL 285
IS 29
BP 22276
EP 22281
DI 10.1074/jbc.M110.102079
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 622YF
UT WOS:000279702200040
PM 20463013
ER
PT J
AU Holmes, EC
AF Holmes, Edward C.
TI The RNA Virus Quasispecies: Fact or Fiction?
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE RNA virus; quasispecies; natural selection; lethal mutagenesis;
robustness
ID DIGITAL ORGANISMS; MUTATION-RATE; EVOLUTION; POPULATION; EXTINCTION
C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Holmes, Edward/0000-0001-9596-3552
NR 18
TC 30
Z9 31
U1 1
U2 7
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 JUL 16
PY 2010
VL 400
IS 3
BP 271
EP 273
DI 10.1016/j.jmb.2010.05.032
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 633ET
UT WOS:000280483100001
PM 20493194
ER
PT J
AU Ventura, CL
Malachowa, N
Hammer, CH
Nardone, GA
Robinson, MA
Kobayashi, SD
DeLeo, FR
AF Ventura, Christy L.
Malachowa, Natalia
Hammer, Carl H.
Nardone, Glenn A.
Robinson, Mary Ann
Kobayashi, Scott D.
DeLeo, Frank R.
TI Identification of a Novel Staphylococcus aureus Two-Component Leukotoxin
Using Cell Surface Proteomics
SO PLOS ONE
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; WALL ASSOCIATED PROTEINS;
NUCLEOTIDE-SEQUENCE; GAMMA-HEMOLYSIN; POLYMORPHONUCLEAR LEUKOCYTES;
GEL-ELECTROPHORESIS; VIRULENCE; GENES; INFECTIONS; LUKF
AB Staphylococcus aureus is a prominent human pathogen and leading cause of bacterial infection in hospitals and the community. Community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 are highly virulent and, unlike hospital strains, often cause disease in otherwise healthy individuals. The enhanced virulence of CA-MRSA is based in part on increased ability to produce high levels of secreted molecules that facilitate evasion of the innate immune response. Although progress has been made, the factors that contribute to CA-MRSA virulence are incompletely defined. We analyzed the cell surface proteome (surfome) of USA300 strain LAC to better understand extracellular factors that contribute to the enhanced virulence phenotype. A total of 113 identified proteins were associated with the surface of USA300 during the late-exponential phase of growth in vitro. Protein A was the most abundant surface molecule of USA300, as indicated by combined Mascot score following analysis of peptides by tandem mass spectrometry. Unexpectedly, we identified a previously uncharacterized two-component leukotoxin-herein named LukS-H and LukF-G (LukGH)-as two of the most abundant surface-associated proteins of USA300. Rabbit antibody specific for LukG indicated it was also freely secreted by USA300 into culture media. We used wild-type and isogenic lukGH deletion strains of USA300 in combination with human PMN pore formation and lysis assays to identify this molecule as a leukotoxin. Moreover, LukGH synergized with PVL to enhance lysis of human PMNs in vitro, and contributed to lysis of PMNs after phagocytosis. We conclude LukGH is a novel two-component leukotoxin with cytolytic activity toward neutrophils, and thus potentially contributes to S. aureus virulence.
C1 [Ventura, Christy L.; Malachowa, Natalia; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Hammer, Carl H.; Nardone, Glenn A.; Robinson, Mary Ann] NIAID, Res Technol Branch, NIH, Rockville, MD USA.
RP Ventura, CL (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
EM fdeleo@niaid.nih.gov
OI Ventura, Christy/0000-0002-5084-1567; DeLeo, Frank/0000-0003-3150-2516
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
TC 96
Z9 96
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 16
PY 2010
VL 5
IS 7
AR e11634
DI 10.1371/journal.pone.0011634
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 626QE
UT WOS:000279980800019
PM 20661294
ER
PT J
AU Olivotto, I
Maron, BJ
Appelbaum, E
Harrigan, CJ
Salton, C
Gibson, CM
Udelson, JE
O'Donnell, C
Lesser, JR
Manning, WJ
Maron, MS
AF Olivotto, Iacopo
Maron, Barry J.
Appelbaum, Evan
Harrigan, Caitlin J.
Salton, Carol
Gibson, C. Michael
Udelson, James E.
O'Donnell, Christopher
Lesser, John R.
Manning, Warren J.
Maron, Martin S.
TI Spectrum and Clinical Significance of Systolic Function and Myocardial
Fibrosis Assessed by Cardiovascular Magnetic Resonance in Hypertrophic
Cardiomyopathy
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; LATE GADOLINIUM ENHANCEMENT; DELAYED
ENHANCEMENT; DYSFUNCTION; PREVALENCE; ECHOCARDIOGRAPHY; IMPAIRMENT;
PROFILE; FLOW
AB In hypertrophic cardiomyopathy (HCM), the clinical significance attributable to the broad range of left ventricular (LV) systolic function, assessed as the ejection fraction (EF), is incompletely resolved. We evaluated the EF using cardiovascular magnetic resonance (CMR) imaging in a large cohort of patients with HCM with respect to the clinical status and evidence of left ventricular remodeling with late gadolinium enhancement (LGE). CMR imaging was performed in 310 consecutive patients, aged 42 +/- 17 years. The EF in patients with HCM was 71 +/- 10% (range 28% to 89%), exceeding that of 606 healthy controls without cardiovascular disease (66 +/- 5%, p <0.001). LGE reflecting LV remodeling showed an independent, inverse relation to the EF (B-0.69, 95% confidence interval -0.86 to -0.52; p <0.001) and was greatest in patients with an EF <50%, in whom it constituted a median value of 29% of the LV volume (interquartile range 16% to 40%). However, the substantial subgroup with low-normal EF values of 50% to 65% (n = 45; 15% of the whole cohort), who were mostly asymptomatic or mildly symptomatic (37 or 82% with New York Heart Association functional class I to II), showed substantial LGE (median 5% of LV volume, interquartile range 2% to 10%). This overlapped with the subgroup with systolic dysfunction and significantly exceeded that of patients with an EF of 66% to 75% and >75% (median 2% of the LV volume, interquartile range 1.5% to 4%; p <0.01). In conclusion, in a large cohort of patients with HCM, a subset of patients with low-normal EF values (50% to 65%) was identified by contrast-enhanced CMR imaging as having substantial degrees of LGE, suggesting a transition phase, potentially heralding advanced LV remodeling and systolic dysfunction, with implications for clinical surveillance and management. (C) 2010 Published by Elsevier Inc. (Am J Cardiol 2010;106:261-267)
C1 [Olivotto, Iacopo] Azienda Osped Univ Careggi, Referral Ctr Myocardial Dis, Florence, Italy.
[Maron, Barry J.; Lesser, John R.] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA.
[Appelbaum, Evan; Salton, Carol; Gibson, C. Michael; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA USA.
[Appelbaum, Evan; Harrigan, Caitlin J.; Salton, Carol; Gibson, C. Michael; Manning, Warren J.] Harvard Univ, Sch Med, PERFUSE Core & Angiog Lab, Boston, MA USA.
[Appelbaum, Evan; Harrigan, Caitlin J.; Salton, Carol; Gibson, C. Michael; Manning, Warren J.] Harvard Univ, Sch Med, Data Coordinating Ctr, Boston, MA USA.
[Udelson, James E.; Maron, Martin S.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
[O'Donnell, Christopher] Framingham Heart Ctr, NHLBI, Framingham, MA USA.
RP Olivotto, I (reprint author), Azienda Osped Univ Careggi, Referral Ctr Myocardial Dis, Florence, Italy.
EM olivottoi@aou-careggi.toscana.it
NR 30
TC 61
Z9 65
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2010
VL 106
IS 2
BP 261
EP 267
DI 10.1016/j.amjcard.2010.03.020
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 628OY
UT WOS:000280131100020
PM 20599013
ER
PT J
AU Steiner, AZ
D'Aloisio, AA
DeRoo, LA
Sandler, DP
Baird, DD
AF Steiner, Anne Z.
D'Aloisio, Aimee A.
DeRoo, Lisa A.
Sandler, Dale P.
Baird, Donna D.
TI Association of Intrauterine and Early-Life Exposures With Age at
Menopause in the Sister Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE diethylstilbestrol; menopause; pregnancy; prenatal exposure delayed
effects; risk factors
ID PREMATURE OVARIAN FAILURE; DIETHYLSTILBESTROL IN-UTERO; BRITISH BIRTH
COHORT; NATURAL MENOPAUSE; RISK-FACTORS; GERM-CELLS; WOMEN;
REPRODUCIBILITY; FOLLICLES; VALIDITY
AB Oocytes are formed in utero; menopause occurs when the oocyte pool is depleted. The authors hypothesized that early-life events could affect the number of a woman's oocytes and determine age at menopause. To test their hypothesis, the authors conducted a secondary analysis of baseline data from 22,165 participants in the Sister Study (2003-2007) who were aged 35-59 years at enrollment. To estimate the association between early-life events and age at natural menopause, the authors used Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals, adjusting for current age, race/ethnicity, education, childhood family income, and smoking history. Earlier menopause was associated with in-utero diethylstilbestrol exposure (hazard ratio (HR) = 1.45, 95% confidence interval (CI): 1.27, 1.65). Suggestive associations included maternal prepregnancy diabetes (HR = 1.33, 95% CI: 0.89, 1.98) and low birth weight (HR = 1.09, 95% CI: 0.99, 1.20). Having a mother aged 35 years or older at birth appeared to be associated with a later age at menopause (HR = 0.95, 95% CI: 0.89, 1.01). Birth order, in-utero smoke exposure, and having been breastfed were not related to age at menopause. In-utero and perinatal events may subsequently influence age at menopause.
C1 [Steiner, Anne Z.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA.
[D'Aloisio, Aimee A.; DeRoo, Lisa A.; Sandler, Dale P.; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Steiner, AZ (reprint author), Univ N Carolina, Sch Med, Dept Obstet & Gynecol, CB 7570,Old Clin Bldg, Chapel Hill, NC 27599 USA.
EM asteiner@med.unc.edu
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health, National Institute of Environmental
Health Sciences [ZO1 ES 044005]; University of North Carolina Women's
Reproductive Health Research Center [K12 HD 050113]
FX This work was supported, in part, by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences (grant ZO1 ES 044005), and the University of North
Carolina Women's Reproductive Health Research Center (grant K12 HD
050113).
NR 35
TC 22
Z9 22
U1 0
U2 4
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 JUL 15
PY 2010
VL 172
IS 2
BP 140
EP 148
DI 10.1093/aje/kwq092
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 630HM
UT WOS:000280263900004
PM 20534821
ER
PT J
AU Vira, S
Mekhedov, E
Humphrey, G
Blank, PS
AF Vira, Shaleen
Mekhedov, Elena
Humphrey, Glen
Blank, Paul S.
TI Fluorescent-labeled antibodies: Balancing functionality and degree of
labeling
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Antibody; Avidity; Fluorophore/protein ratio; Kinetic ELISA; Global
fitting; Optimal labeling
ID SURFACE-IMMOBILIZED ANTIGEN; LINKED-IMMUNOSORBENT-ASSAY;
MONOCLONAL-ANTIBODIES; PLASMON RESONANCE; FLOW-CYTOMETRY;
ISOTHIOCYANATE; CONJUGATION; BINDING; MEMBRANES; FLUOROCHROMES
AB A critical assumption in using labeled antibodies is that the conjugation reaction has no deleterious effects on antibody avidity. This study demonstrates that this assumption need not hold true and presents a methodology to quantitatively determine the degree of inactivation and/or changes in antibody-antigen binding that can occur with conjugation. Fluorescein isothiocyanate (FITC) was conjugated to a mouse monoclonal antibody, Fc125, against hemagglutinin (HA) using varying fluorophore/protein (F:P) labeling ratios. Antibody binding, as a function of the F:P labeling ratio, was evaluated using a kinetic enzyme-linked immunosorbent assay (ELISA) and analyzed using global fitting. A two-parameter adjustment of the antibody concentration and the maximum rate was sufficient to describe the rate changes. The concentration parameter dominated the rate changes, consistent with the hypothesis that the coupling reaction inactivated an increasing fraction of the antibody population with a smaller change (similar to 15% at the highest F:P ratio) in antibody-antigen binding. An optimal F:P ratio that minimized both inactivation and unlabeled antibody was calculated. This procedure can be used to prepare functional, labeled antibody reagents with defined activity and can aid in quantitative applications where the stoichiometry and functionality of the labeled antibody are critical. Published by Elsevier Inc.
C1 [Vira, Shaleen; Mekhedov, Elena; Humphrey, Glen; Blank, Paul S.] Eunice Kennedy Shriver NICHHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Blank, PS (reprint author), Eunice Kennedy Shriver NICHHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM blankp@mail.nih.gov
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported by the Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 44
TC 42
Z9 43
U1 0
U2 14
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 JUL 15
PY 2010
VL 402
IS 2
BP 146
EP 150
DI 10.1016/j.ab.2010.03.036
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 606KM
UT WOS:000278423900005
PM 20362543
ER
PT J
AU Minton, AP
AF Minton, Allen P.
TI Analysis of membrane binding equilibria of peripheral proteins:
Allowance for excluded area of bound protein (vol 397, pg 247, 2010)
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Correction
C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUL 15
PY 2010
VL 402
IS 2
BP 206
EP 206
DI 10.1016/j.ab.2010.03.023
PG 1
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 606KM
UT WOS:000278423900016
ER
PT J
AU Lih, FB
Titus, MA
Mohler, JL
Tomer, KB
AF Lih, Fred Bjorn
Titus, Mark A.
Mohler, James L.
Tomer, Kenneth B.
TI Atmospheric Pressure Photoionization Tandem Mass Spectrometry of
Androgens in Prostate Cancer
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID LIQUID-CHROMATOGRAPHY; ELECTROSPRAY-IONIZATION; DUTASTERIDE; CASTRATION;
TRIAL; TESTOSTERONE; INHIBITOR; PROFILES; SERUM; CYP17
AB Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-alpha-androstanedione required detection of a novel parent ion, [M + 15](+). The nature of this parent ion was explored, and the method was applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization.
C1 [Lih, Fred Bjorn; Tomer, Kenneth B.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Titus, Mark A.; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
RP Tomer, KB (reprint author), NIEHS, NIH, US Dept HHS, MD F0-03,POB 12233, Res Triangle Pk, NC 27709 USA.
RI Tomer, Kenneth/E-8018-2013
FU National Institute of Environmental Health Sciences/National institutes
of Health [ES 050167]; National Cancer Center [PO1 NCI-CA-77739,
CA016156]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Environmental Health Sciences/National
institutes of Health (ES 050167) and Grants PO1# NCI-CA-77739 to J.L.M.
and CA016156 National Cancer Center Support Grant to Roswell Park Cancer
Institute.
NR 27
TC 14
Z9 14
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD JUL 15
PY 2010
VL 82
IS 14
BP 6000
EP 6007
DI 10.1021/ac100460x
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 623GU
UT WOS:000279727800013
PM 20560527
ER
PT J
AU Keene, AM
Balasubramanian, R
Lloyd, J
Shainberg, A
Jacobson, KA
AF Keene, Athena M.
Balasubramanian, Ramachandran
Lloyd, John
Shainberg, Asher
Jacobson, Kenneth A.
TI Multivalent dendrimeric and monomeric adenosine agonists attenuate cell
death in HL-1 mouse cardiomyocytes expressing the A(3) receptor
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Cardioprotection; Nucleoside; G protein-coupled receptor; Dendrimers;
Polymeric drugs; HL-1 cells
ID RHEUMATOID-ARTHRITIS; LUNG INJURY; KAPPA-B; CARDIOPROTECTION;
OVEREXPRESSION; REPERFUSION; ANTAGONISTS; PHYSIOLOGY; ISCHEMIA; PATHWAYS
AB Multivalent dendrimeric conjugates of GPCR ligands may have increased potency or selectivity in comparison to monomeric ligands, a phenomenon that was tested in a model of cytoprotection in mouse HL-1 cardiomyocytes. Quantitative RT-PCR indicated high expression levels of endogenous A(1) and A(2A) adenosine receptors (ARs), but not of A(2B) and A(3)ARs. Activation of the heterologously expressed human A(3)AR in HL-1 cells by AR agonists significantly attenuated cell damage following 4 h exposure to H2O2 (750 mu M) but not in untransfected cells. The A(3) agonist IB-MECA (EC50 3.8 mu M) and the non-selective agonist NECA (EC50 3.9 mu M) protected A(3) AR-transfected cells against H2O2 in a concentration-dependent manner, as determined by lactate dehydrogenase release. A generation 5.5 PAMAM (polyamidoamine) dendrimeric conjugate of a N-6-chain-functionalized adenosine agonist was synthesized and its mass indicated an average of 60 amide-linked nucleoside moieties out of 256 theoretical attachment sites. It non-selectively activated the A3AR to inhibit forskolin-stimulated cAMP formation (IC50 66 nM) and, similarly, protected A(3)-transfected HL-1 cells from apoptosis-inducing H2O2 with greater potency (IC50 35 nM) than monomeric nucleosides. Thus, a PAMAM conjugate retained AR binding affinity and displayed greatly enhanced cardioprotective potency. Published by Elsevier Inc.
C1 [Keene, Athena M.; Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA.
[Lloyd, John] NIDDK, Mass Spectrometry Facil, LBC, NIH, Bethesda, MD 20892 USA.
[Shainberg, Asher] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes and Digestive and Kidney Diseases.
We thank Lena Yoo (NIDDK) for proofreading this manuscript.
NR 41
TC 11
Z9 11
U1 0
U2 1
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 JUL 15
PY 2010
VL 80
IS 2
BP 188
EP 196
DI 10.1016/j.bcp.2010.03.020
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 599UN
UT WOS:000277939300005
PM 20346920
ER
PT J
AU Carroll, HD
Kann, MG
Sheetlin, SL
Spouge, JL
AF Carroll, Hyrum D.
Kann, Maricel G.
Sheetlin, Sergey L.
Spouge, John L.
TI Threshold Average Precision (TAP-k): a measure of retrieval designed for
bioinformatics
SO BIOINFORMATICS
LA English
DT Article
ID SEQUENCE COMPARISON METHODS; PROTEIN-SEQUENCE; ROC ANALYSIS; BLAST;
PERFORMANCE; ACCURACY; SEARCHES; AREA
AB Motivation: Since database retrieval is a fundamental operation, the measurement of retrieval efficacy is critical to progress in bioinformatics. This article points out some issues with current methods of measuring retrieval efficacy and suggests some improvements. In particular, many studies have used the pooled receiver operating characteristic for n irrelevant records (ROC(n)) score, the area under the ROC curve (AUC) of a 'pooled' ROC curve, truncated at n irrelevant records. Unfortunately, the pooled ROC(n) score does not faithfully reflect actual usage of retrieval algorithms. Additionally, a pooled ROC(n) score can be very sensitive to retrieval results from as little as a single query.
Methods: To replace the pooled ROC(n) score, we propose the Threshold Average Precision (TAP-k), a measure closely related to the well-known average precision in information retrieval, but reflecting the usage of E-values in bioinformatics. Furthermore, in addition to conditions previously given in the literature, we introduce three new criteria that an ideal measure of retrieval efficacy should satisfy.
Results: PSI-BLAST, GLOBAL, HMMER and RPS-BLAST provided examples of using the TAP-k and pooled ROC(n) scores to evaluate sequence retrieval algorithms. In particular, compelling examples using real data highlight the drawbacks of the pooled ROC(n) score, showing that it can produce evaluations skewing far from intuitive expectations. In contrast, the TAP-k satisfies most of the criteria desired in an ideal measure of retrieval efficacy.
C1 [Carroll, Hyrum D.; Sheetlin, Sergey L.; Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Kann, Maricel G.] Univ Maryland, Baltimore, MD 21250 USA.
RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM spouge@ncbi.nlm.nih.gov
RI Kann, Maricel/E-5701-2012
FU National Institutes of Health (NIH) [1K22CA143148]; NIH, National
Library of Medicine
FX National Institutes of Health (NIH) (1K22CA143148 to M.G.K.); Intramural
Research Program of the NIH, National Library of Medicine (in part).
NR 27
TC 14
Z9 15
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 JUL 15
PY 2010
VL 26
IS 14
BP 1708
EP 1713
DI 10.1093/bioinformatics/btq270
PG 6
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 620BQ
UT WOS:000279474400005
PM 20505002
ER
PT J
AU Bozdag, S
Li, AG
Wuchty, S
Fine, HA
AF Bozdag, Serdar
Li, Aiguo
Wuchty, Stefan
Fine, Howard A.
TI FastMEDUSA: a parallelized tool to infer gene regulatory networks
SO BIOINFORMATICS
LA English
DT Article
ID EXPRESSION
AB Motivation: In order to construct gene regulatory networks of higher organisms from gene expression and promoter sequence data efficiently, we developed FastMEDUSA. In this parallelized version of the regulatory network-modeling tool MEDUSA, expression and sequence data are shared among a user-defined number of processors on a single multi-core machine or cluster. Our results show that FastMEDUSA allows a more efficient utilization of computational resources. While the determination of a regulatory network of brain tumor in Homo sapiens takes 12 days with MEDUSA, FastMEDUSA obtained the same results in 6 h by utilizing 100 processors.
C1 [Bozdag, Serdar; Li, Aiguo; Wuchty, Stefan; Fine, Howard A.] NINDS, Neurooncol Branch, NCI, Bethesda, MD 20892 USA.
[Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
FU National Institutes of Health; National Cancer Institute
FX Intramural Research Program of the National Institutes of Health;
National Cancer Institute.
NR 10
TC 11
Z9 11
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JUL 15
PY 2010
VL 26
IS 14
BP 1792
EP 1793
DI 10.1093/bioinformatics/btq275
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 620BQ
UT WOS:000279474400022
PM 20513661
ER
PT J
AU Romagnoli, R
Baraldi, PG
Carrion, MD
Cruz-Lopez, O
Tolomeo, M
Grimaudo, S
Di Cristina, A
Pipitone, MR
Balzarini, J
Brancale, A
Hamel, E
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Carrion, Maria Dora
Cruz-Lopez, Olga
Tolomeo, Manlio
Grimaudo, Stefania
Di Cristina, Antonietta
Pipitone, Maria Rosaria
Balzarini, Jan
Brancale, Andrea
Hamel, Ernest
TI Substituted 2-(3 ',4 ',5 '-trimethoxybenzoyl)-benzo[b]thiophene
derivatives as potent tubulin polymerization inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Antiproliferative agents; Tubulin polymerization inhibitors;
Microtubules; Antitumor
ID ANTIMITOTIC AGENTS; BIOLOGICAL EVALUATION; MEDICINAL CHEMISTRY;
ANTITUBULIN AGENTS; COLCHICINE; CANCER; COMBRETASTATIN-A-4; MECHANISM;
PROTEINS; ANALOGS
AB The central role of microtubules in cell division and mitosis makes them a particularly important target for anticancer agents. On our early publication, we found that a series of 2-(3',4',5'-trimethoxybenzoyl)-3-aminobenzo[b]thiophenes exhibited strong antiproliferative activity in the submicromolar range and significantly arrested cells in the G2-M phase of the cell cycle and induced apoptosis. In order to investigate the importance of the amino group at the 3-position of the benzo[b] thiophene skeleton, the corresponding 3-unsubstituted and methyl derivatives were prepared. A novel series of inhibitors of tubulin polymerization, based on the 2-(3,4,5-trimethoxybenzoyl)-benzo[b] thiophene molecular skeleton with a methoxy substituent at the C-4, C-5, C-6 or C-7 position on the benzene ring, was evaluated for antiproliferative activity against a panel of five cancer cell lines, for inhibition of tubulin polymerization and for cell cycle effects. Replacing the methyl group at the C-3 position resulted in increased activity compared with the corresponding 3-unsubstituted counterpart. The structure-activity relationship established that the best activities were obtained with the methoxy group placed at the C-4, C-6 or C-7 position. Most of these compounds exhibited good growth inhibition activity and arrest K562 cells in the G2-M phase via microtubule depolymerization. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Carrion, Maria Dora; Cruz-Lopez, Olga] Univ Ferrara, Dipartimento Sci Farmaceut, I-44121 Ferrara, Italy.
[Tolomeo, Manlio; Grimaudo, Stefania; Di Cristina, Antonietta; Pipitone, Maria Rosaria] Univ Palermo, Dipartimento Biomed Med Interna & Specialist, Palermo, Italy.
[Balzarini, Jan] Rega Inst, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium.
[Brancale, Andrea] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3NB, S Glam, Wales.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato Mortara 17-19, I-44121 Ferrara, Italy.
EM rmr@unife.it; baraldi@unife.it
RI antonietta, di cristina/I-9251-2012; Brancale, Andrea/N-9445-2014;
Carrion, M. Dora/G-8638-2015; Romagnoli, Romeo/G-9887-2015; Baraldi,
Pier Giovanni/B-7933-2017; Cruz-Lopez, Olga /F-3060-2017;
OI Brancale, Andrea/0000-0002-9728-3419; Carrion, M.
Dora/0000-0002-6794-3949; PIPITONE, Rosaria Maria/0000-0002-6721-3962;
Grimaudo, Stefania/0000-0003-3225-4112
FU GOA [10/014]
FX Financial support was provided by GOA (Krediet no. 10/014) of the K. U.
Leuven. The authors would like to thank Mrs. Lizette van Berckelaer, Dr.
Alberto Casolari and Elisa Durini for technical assistance.
NR 30
TC 26
Z9 27
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2010
VL 18
IS 14
BP 5114
EP 5122
DI 10.1016/j.bmc.2010.05.068
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 623MN
UT WOS:000279744700029
PM 20579891
ER
PT J
AU Nishizawa, R
Nishiyama, T
Hisaichi, K
Hirai, K
Habashita, H
Takaoka, Y
Tada, H
Sagawa, K
Shibayama, S
Maeda, K
Mitsuya, H
Nakai, H
Fukushima, D
Toda, M
AF Nishizawa, Rena
Nishiyama, Toshihiko
Hisaichi, Katsuya
Hirai, Keisuke
Habashita, Hiromu
Takaoka, Yoshikazu
Tada, Hideaki
Sagawa, Kenji
Shibayama, Shiro
Maeda, Kenji
Mitsuya, Hiroaki
Nakai, Hisao
Fukushima, Daikichi
Toda, Masaaki
TI Discovery of orally available spirodiketopiperazine-based CCR5
antagonists
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE CCR5; Chemokine; Anti HIV
ID HIV-1 INFECTION; RECEPTOR; ENTRY; CORECEPTOR; COFACTOR; DISEASE; POTENT
AB Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Nishizawa, Rena; Nishiyama, Toshihiko; Hisaichi, Katsuya; Hirai, Keisuke; Habashita, Hiromu; Nakai, Hisao; Toda, Masaaki] Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka 6188585, Japan.
[Tada, Hideaki; Shibayama, Shiro; Fukushima, Daikichi] Ono Pharmaceut Co Ltd, Tsukuba Res Inst, Ibaraki 300424, Japan.
[Takaoka, Yoshikazu] Ono Pharmaceut Co Ltd, Fukui Res Inst, Fukui 9138538, Japan.
[Sagawa, Kenji] Ono Pharmaceut Co Ltd, Osaka 5410056, Japan.
[Maeda, Kenji; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 8600811, Japan.
[Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Nishizawa, R (reprint author), Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka 6188585, Japan.
EM r.nishizawa@ono.co.jp
NR 19
TC 10
Z9 10
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2010
VL 18
IS 14
BP 5208
EP 5223
DI 10.1016/j.bmc.2010.05.057
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 623MN
UT WOS:000279744700039
PM 20542438
ER
PT J
AU Kozaka, T
Nakagawa-Goto, K
Shi, QA
Lai, CY
Hamel, E
Bastow, KF
Brossi, A
Lee, KH
AF Kozaka, Takashi
Nakagawa-Goto, Kyoko
Shi, Qian
Lai, Chin-Yu
Hamel, Ernest
Bastow, Kenneth F.
Brossi, Arnold
Lee, Kuo-Hsiung
TI Antitumor agents 273. Design and synthesis of N-alkyl-thiocolchicinoids
as potential antitumor agents
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE N-Alkylthiocolchinoids; Antitumor agents; Tubulin polymerization
ID COLCHICINE; DERIVATIVES
AB As a part of our continuing study of colchicinoids as therapeutically useful antitumor drugs, thiocolchicine derivatives, including their phosphate and other water soluble salts, were synthesized and evaluated for inhibition of tubulin polymerization and for in vitro cytotoxicity. Three compounds, 7, 10, and 11, showed potent inhibition of tubulin assembly (IC(50) = 0.88-1.1 mu M). In addition, compound 7, a water soluble succinic acid salt of N-deacetylthiocolchicine ( 4), showed potent cytotoxicity against a panel of tumor cell lines, suggesting it might be a potential lead to be developed as a therapeutic antitumor agent. Compound 8, a water soluble succinic acid salt of N,N-dimethyl-N-deacetylthiocolchicine ( 5), showed selective activities against HCT-8 and SK-BR-3 cells. N,N-Diethyl-N-deacetylthiocolchicine ( 6) seemed not to be a substrate for the P-gp efflux pump, based on the similar ED(50) values obtained against P-gp over-expressing KBvin (0.0146 mu g/mL) cells and the parent KB (0.0200 mu g/mL) cell line. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Kozaka, Takashi; Nakagawa-Goto, Kyoko; Shi, Qian; Lai, Chin-Yu; Brossi, Arnold; Lee, Kuo-Hsiung] Univ N Carolina, Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
[Hamel, Ernest] NIH, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[Bastow, Kenneth F.] Univ N Carolina, Eshelman Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
RP Lee, KH (reprint author), Univ N Carolina, Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
EM khlee@unc.edu
RI GOTO, Kyoko/D-8389-2015
OI GOTO, Kyoko/0000-0002-1642-6538
FU National Cancer Institute, NIH [CA17625]
FX This study was supported by NIH grant CA17625 from the National Cancer
Institute awarded to K.H. Lee.
NR 13
TC 6
Z9 6
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUL 15
PY 2010
VL 20
IS 14
BP 4091
EP 4094
DI 10.1016/j.bmcl.2010.05.081
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 617CQ
UT WOS:000279258800022
PM 20542428
ER
PT J
AU Cheruku, P
Keffer, JL
Dogo-Isonagie, C
Bewley, CA
AF Cheruku, Pradeep
Keffer, Jessica L.
Dogo-Isonagie, Cajetan
Bewley, Carole A.
TI Motualevic acids and analogs: Synthesis and antimicrobial
structure-activity relationships
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Antibacterial; Gram-positive bacteria; Marine natural product; Dibromo
olefin
ID GRAM-POSITIVE INFECTIONS; NATURAL-PRODUCTS; ANTIBACTERIAL; DAPTOMYCIN;
DISCOVERY
AB Synthesis of the marine natural products motualevic acids A, E, and analogs in which modi. cations have been made to the omega-brominated lipid (E)-14,14-dibromotetra-deca-2,13-dienoic acid or amino acid unit are reported, together with antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Enterococcus faecium, and vancomycin-resistant Enterococcus. Published by Elsevier Ltd.
C1 [Cheruku, Pradeep; Keffer, Jessica L.; Dogo-Isonagie, Cajetan; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
RI Cheruku, Pradeep/A-2176-2012;
OI Keffer, Jessica/0000-0002-0302-3588
FU NIH Intramural Research Program (NIDDK)
FX We thank J. R. Lloyd and N. Whittaker for mass spectral data. This work
was supported by the NIH Intramural Research Program (NIDDK) and the
Intramural AIDS Targeted Antiviral Program, Office of the Director, NIH
(C.A.B).
NR 21
TC 4
Z9 4
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 JUL 15
PY 2010
VL 20
IS 14
BP 4108
EP 4111
DI 10.1016/j.bmcl.2010.05.073
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 617CQ
UT WOS:000279258800026
PM 20538459
ER
PT J
AU Li, AG
Bozdag, S
Kotliarov, Y
Fine, HA
AF Li, Aiguo
Bozdag, Serdar
Kotliarov, Yuri
Fine, Howard A.
TI GliomaPredict: a clinically useful tool for assigning glioma patients to
specific molecular subtypes
SO BMC MEDICAL INFORMATICS AND DECISION MAKING
LA English
DT Article
ID GENE-EXPRESSION; CLASSIFICATION; SUBCLASSES; PATHWAYS
AB Background: Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine.
Results: We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework.
Conclusions: GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.
C1 [Li, Aiguo; Bozdag, Serdar; Kotliarov, Yuri; Fine, Howard A.] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
RI Kotliarov, Yuri/B-6938-2017
NR 16
TC 10
Z9 10
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6947
J9 BMC MED INFORM DECIS
JI BMC Med. Inform. Decis. Mak.
PD JUL 15
PY 2010
VL 10
AR 38
DI 10.1186/1472-6947-10-38
PG 5
WC Medical Informatics
SC Medical Informatics
GA 667NJ
UT WOS:000283199900001
PM 20633285
ER
PT J
AU Weaver, KE
Rowland, JH
Bellizzi, KM
Aziz, NM
AF Weaver, Kathryn E.
Rowland, Julia H.
Bellizzi, Keith M.
Aziz, Noreen M.
TI Forgoing Medical Care Because of Cost Assessing Disparities in
Healthcare Access Among Cancer Survivors Living in the United States
SO CANCER
LA English
DT Article
DE cancer; healthcare disparities; long-term survivors; health services
accessibility
ID COLORECTAL-CANCER; PREVENTIVE CARE; OPPORTUNITIES; BARRIERS; QUALITY;
AGE
AB BACKGROUND: Many US cancer survivors live years after diagnosis, which emphasizes the importance of healthcare access for survivors. It is not known whether having cancer has an impact on disparities in healthcare access that are present in the general population. The objective of this study was to examine the prevalence of forgoing care because of financial concerns in a representative sample of US adults to determine whether cancer history and race/ethnicity are associated with the likelihood of forgoing medical care. METHODS: Data from the US National Health Interview Survey (NHS) from 2003 to 2006 were used to identify 6602 adult cancer survivors and 104,364 individuals who had no history of cancer. Self-reports of forgoing medical care services because of cost were analyzed according to cancer history and race/ethnicity using multivariate logistic regression. RESULTS: The prevalence of forgoing care because of cost among cancer survivors was 7.8% for medical care, 9.9% for prescription medications, 11.3% for dental care, and 2.7% for mental healthcare. Cancer survivors aged <65 years were more likely to delay or forgo all types of medical care compared with adults who did not have a history of cancer. Hispanic and black cancer survivors were more likely to forgo prescription medications and dental care than white survivors. Disparities among cancer survivors largely were reflective of those in the general adult population. CONCLUSIONS: More than 2 million US cancer survivors did not get 1 or more needed medical services because of financial concerns during the studied period. Future research needs to examine the impact of forgoing care on survivors' quality of life and survival. Cancer 2010;116:3493-504. Published 2010 by the American Cancer Society*
C1 [Weaver, Kathryn E.; Rowland, Julia H.; Aziz, Noreen M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Weaver, Kathryn E.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA.
[Bellizzi, Keith M.] Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT USA.
RP Weaver, KE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM keweaver@wfubmc.edu
FU NCI NIH HHS [HHSN261200900553P, L30 CA153405-01]
NR 21
TC 65
Z9 66
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2010
VL 116
IS 14
BP 3493
EP 3504
DI 10.1002/cncr.25209
PG 12
WC Oncology
SC Oncology
GA 623PM
UT WOS:000279754300025
PM 20549763
ER
PT J
AU Barkan, D
El Touny, LH
Michalowski, AM
Smith, JA
Chu, I
Davis, AS
Webster, JD
Hoover, S
Simpson, RM
Gauldie, J
Green, JE
AF Barkan, Dalit
El Touny, Lara H.
Michalowski, Aleksandra M.
Smith, Jane Ann
Chu, Isabel
Davis, Anne Sally
Webster, Joshua D.
Hoover, Shelley
Simpson, R. Mark
Gauldie, Jack
Green, Jeffrey E.
TI Metastatic Growth from Dormant Cells Induced by a Col-I-Enriched
Fibrotic Environment
SO CANCER RESEARCH
LA English
DT Article
ID INVASIVE DUCTAL CARCINOMA; BREAST-CANCER; TUMOR DORMANCY; BONE-MARROW;
EXPRESSION; MICROENVIRONMENT; PROLIFERATION; PHENOTYPE; KINASE;
MICROMETASTASIS
AB Breast cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy seems to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. We now show that the induction of fibrosis, associated with deposition of type I collagen (Col-I) in the in vivo metastatic microenvironment, induces dormant D2.0R cells to form proliferative metastatic lesions through beta 1-integrin signaling. In vitro studies using a three-dimensional culture system modeling dormancy showed that Col-I induces quiescent D2.0R cells to proliferate through beta 1-integrin activation of SRC and focal adhesion kinase, leading to extracellular signal-regulated kinase (ERK)-dependent myosin light chain phosphorylation by myosin light chain kinase and actin stress fiber formation. Blocking beta 1-integrin, Src, ERK, or myosin light chain kinase by short hairpin RNA or pharmacologic approaches inhibited Col-I-induced activation of this signaling cascade, cytoskeletal reorganization, and proliferation. These findings show that fibrosis with Col-I enrichment at the metastatic site may be a critical determinant of cytoskeletal reorganization in dormant tumor cells, leading to their transition from dormancy to metastatic growth. Thus, inhibiting Col-I production, its interaction with beta 1-integrin, and downstream signaling of beta 1-integrin may be important strategies for preventing or treating recurrent metastatic disease. Cancer Res; 70(14); 5706-16. (C)2010 AACR.
C1 [Barkan, Dalit; El Touny, Lara H.; Michalowski, Aleksandra M.; Chu, Isabel; Webster, Joshua D.; Hoover, Shelley; Simpson, R. Mark; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Davis, Anne Sally] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Smith, Jane Ann; Gauldie, Jack] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
EM jegreen@nih.gov
OI Davis, Anne/0000-0001-5711-3936
FU NIH, Center for Cancer Research, National Cancer Institute; Canadian
Institutes of Health Research
FX This research was supported by the Intramural Program of NIH, Center for
Cancer Research, National Cancer Institute, and the Canadian Institutes
of Health Research.
NR 40
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U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2010
VL 70
IS 14
BP 5706
EP 5716
DI 10.1158/0008-5472.CAN-09-2356
PG 11
WC Oncology
SC Oncology
GA 626GV
UT WOS:000279955300007
PM 20570886
ER
PT J
AU Huff, LM
Sackett, DL
Poruchynsky, MS
Fojo, T
AF Huff, Lyn M.
Sackett, Dan L.
Poruchynsky, Marianne S.
Fojo, Tito
TI Microtubule-Disrupting Chemotherapeutics Result in Enhanced
Proteasome-Mediated Degradation and Disappearance of Tubulin in Neural
Cells
SO CANCER RESEARCH
LA English
DT Article
ID PERIPHERAL NERVOUS-SYSTEM; CANCER-CELLS; CENTROMERE DYNAMICS; CYCLE
REGULATION; BETA-TUBULINS; VINCRISTINE; NEUROPATHY; MECHANISM; TARGET;
DRUGS
AB We sought to examine the effects of microtubule-targeting agents (MTA) on neural cells to better understand the problem of neurotoxicity, their principal side effect, and to possibly develop a model of clinical toxicity. Studies showed that microtubule-depolymerizing agents (MDA) not only disassembled microtubules in neural HCN2 cells but also led to rapid disappearance of tubulin, and that this was specific for MDAs. Tubulin levels decreased to 20% as early as 8 hours after adding vincristine, and to 1% to 30% (mean, 9.8 +/- 7.6%; median of 7%) after 100 nmol/L vincristine for 24 hours. This disappearance was reversible. An increase in both glu-terminated and acetylated tubulin, markers of stable tubulin, preceded reaccumulation of soluble tubulin, suggesting a priority for stabilizing tubulin first as microtubules before replenishing the soluble pool. Similar results were shown with other MDAs. Furthermore, microtubule reassembly did not arise from a central focus but instead appeared to involve dispersed nucleation, as evidenced by the appearance of small, stable microtubule stubs throughout the cytoplasm. In contrast, experiments with four nonneural "normal" cell lines and four cancer cell lines resulted in microtubule destabilization but only modest tubulin degradation. Evidence for proteasome-mediated degradation was obtained by demonstrating that adding a proteasome inhibitor before vincristine prevented tubulin disappearance. In summary, MDAs lead to rapid disappearance of tubulin in neural but not in other normal or cancer cells. These results underscore the fine control that occurs in neural cells and may further our understanding of neurotoxicity following MDAs. Cancer Res; 70(14); 5870-9. (C)2010 AACR.
C1 [Huff, Lyn M.; Poruchynsky, Marianne S.; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Bethesda, MD USA.
RP Huff, LM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lyn@mail.nih.gov; tfojo@helix.nih.gov
FU National Cancer Institute, NIH (Bethesda, MD)
FX Intramural Research Program, National Cancer Institute, NIH (Bethesda,
MD).
NR 34
TC 11
Z9 11
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2010
VL 70
IS 14
BP 5870
EP 5879
DI 10.1158/0008-5472.CAN-09-4281
PG 10
WC Oncology
SC Oncology
GA 626GV
UT WOS:000279955300023
PM 20587529
ER
PT J
AU Ahn, RW
Chen, F
Chen, HM
Stern, ST
Clogston, JD
Patri, AK
Raja, MR
Swindell, EP
Parimi, V
Cryns, VL
O'Halloran, TV
AF Ahn, Richard W.
Chen, Feng
Chen, Haimei
Stern, Stephan T.
Clogston, Jeffrey D.
Patri, Anil K.
Raja, Meera R.
Swindell, Elden P.
Parimi, Vamsi
Cryns, Vincent L.
O'Halloran, Thomas V.
TI A Novel Nanoparticulate Formulation of Arsenic Trioxide with Enhanced
Therapeutic Efficacy in a Murine Model of Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHASE-II TRIAL; CELLS IN-VITRO; LIPOSOMES; TUMORS; AS2O3; ENCAPSULATION;
PATTERNS; SUBTYPES; DRUGS; VIVO
AB Purpose: The clinical success of arsenic trioxide (As(2)O(3)) in hematologic malignancies has not been replicated in solid tumors due to poor pharmacokinetics and dose-limiting toxicity. We have developed a novel nanoparticulate formulation of As(2)O(3) encapsulated in liposomal vesicles or "nanobins" [(NB(Ni, As)] to overcome these hurdles. We postulated that nanobin encapsulation of As(2)O(3) would improve its therapeutic index against clinically aggressive solid tumors, such as triple-negative breast carcinomas.
Experimental Design: The cytotoxicity of NB(Ni, As), the empty nanobin, and free As(2)O(3) was evaluated against a panel of human breast cancer cell lines. The plasma pharmacokinetics of NB(Ni, As) and free As(2)O(3) were compared in rats to measure drug exposure. In addition, the antitumor activity of these agents was evaluated in an orthotopic model of human triple-negative breast cancer.
Results: The NB(Ni, As) agent was much less cytotoxic in vitro than free As(2)O(3) against a panel of human breast cancer cell lines. In contrast, NB(Ni, As) dramatically potentiated the therapeutic efficacy of As(2)O(3) in vivo in an orthotopic model of triple-negative breast cancer. Reduced plasma clearance, enhanced tumor uptake, and induction of tumor cell apoptosis were observed for NB(Ni, As).
Conclusions: Nanobin encapsulation of As(2)O(3) improves the pharmacokinetics and antitumor efficacy of this cytotoxic agent in vivo. Our findings demonstrate the therapeutic potential of this nanoscale agent and provide a foundation for future clinical studies in breast cancer and other solid tumors. Clin Cancer Res; 16(14); 3607-17. (C) 2010 AACR.
C1 [O'Halloran, Thomas V.] Northwestern Univ, Dept Chem, Chem Life Proc Inst, Evanston, IL 60208 USA.
[Chen, Feng; Cryns, Vincent L.] Northwestern Univ, Dept Med, Cell Death Regulat Lab, Chicago, IL 60611 USA.
[Chen, Feng; Cryns, Vincent L.] Northwestern Univ, Dept Cell & Mol Biol, Cell Death Regulat Lab, Evanston, IL 60208 USA.
[Parimi, Vamsi] Northwestern Univ, Pathol Core Facil, Feinberg Sch Med, Evanston, IL 60208 USA.
[Ahn, Richard W.; Chen, Feng; Chen, Haimei; Raja, Meera R.; Swindell, Elden P.; Parimi, Vamsi; Cryns, Vincent L.; O'Halloran, Thomas V.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Stern, Stephan T.; Clogston, Jeffrey D.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP O'Halloran, TV (reprint author), Northwestern Univ, Dept Chem, Chem Life Proc Inst, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM v-cryns@northwestern.edu; t-ohalloran@northwestern.edu
RI Parimi, Vamsi/P-5675-2014; Nanotechnology Characterization Lab,
NCL/K-8454-2012
FU NIH [R01GM054111]; Center of Cancer Nanotechnology Excellence
[U54CA119341]; Robert H. Lurie Comprehensive Cancer Center
[P30CA060553]; CDMRP Breast Cancer Research Program [BC073413,
BC076723]; Breast Cancer Research Foundation; Malkin Fellowship;
National Cancer Institute, NIH [HHSN261200800001E]
FX NIH grants R01GM054111, The Center of Cancer Nanotechnology Excellence
U54CA119341, and the Robert H. Lurie Comprehensive Cancer Center Core
Grant P30CA060553; the CDMRP Breast Cancer Research Program BC073413 and
BC076723, the Breast Cancer Research Foundation, and the Malkin
Fellowship. NCL work was funded in whole or in part with federal funds
from the National Cancer Institute, NIH, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 42
TC 39
Z9 40
U1 0
U2 19
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 JUL 15
PY 2010
VL 16
IS 14
BP 3607
EP 3617
DI 10.1158/1078-0432.CCR-10-0068
PG 11
WC Oncology
SC Oncology
GA 625NW
UT WOS:000279903100010
PM 20519360
ER
PT J
AU Fakih, MG
Fetterly, G
Egorin, MJ
Muindi, JR
Espinoza-Delgado, I
Zwiebel, JA
Litwin, A
Holleran, JL
Wang, KS
Diasio, RB
AF Fakih, Marwan G.
Fetterly, Gerald
Egorin, Merrill J.
Muindi, Josephia R.
Espinoza-Delgado, Igor
Zwiebel, James A.
Litwin, Alan
Holleran, Julianne L.
Wang, Kangsheng
Diasio, Robert B.
TI A Phase I, Pharmacokinetic, and Pharmacodynamic Study of Two Schedules
of Vorinostat in Combination with 5-Fluorouracil and Leucovorin in
Patients with Refractory Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITORS; THYMIDYLATE SYNTHASE GENE; HUMAN
COLON-CANCER; DISSEMINATED COLORECTAL-CANCER; MESSENGER-RNA LEVELS;
CELL-LINES; ANTICANCER AGENTS; HDAC INHIBITION; EXPRESSION; FLUOROURACIL
AB Purpose: We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat x 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks.
Experimental Design: Vorinostat doses were escalated in a standard 3 x 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m(2) i.v. over 2 hours followed by FU 400 mg/m(2) i.v. bolus and 2,400 mg/m(2) over 46 hours (sLV5FU2).
Results: Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU.
Conclusions: The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily x 3 or 600 mg orally twice daily x 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. Clin Cancer Res; 16(14); 3786-94. ((c))2010 AACR.
C1 [Fakih, Marwan G.; Fetterly, Gerald; Muindi, Josephia R.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Litwin, Alan] Roswell Pk Canc Inst, Dept Radiol, Buffalo, NY 14263 USA.
[Fakih, Marwan G.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Buffalo, NY 14260 USA.
[Egorin, Merrill J.; Holleran, Julianne L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Egorin, Merrill J.; Holleran, Julianne L.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA.
[Egorin, Merrill J.; Holleran, Julianne L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Espinoza-Delgado, Igor; Zwiebel, James A.] NIH, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Wang, Kangsheng; Diasio, Robert B.] Mayo Clin, Ctr Canc, Rochester, MN USA.
RP Fakih, MG (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA.
EM marwan.fakih@roswellpark.org
FU National Cancer Institute [N01-CO-124001, 25XS115-Task Order 2, P30
CA47904]; Institutional Cancer Center [CA16056]
FX Cancer Therapy Evaluation Program, the National Cancer Institute;
Institutional Cancer Center Support Grant CA16056; American Cancer
Society Grant MRSG-04-270-01; NCI contract N01-CO-124001, subcontract
25XS115-Task Order 2; and NCI grant P30 CA47904.
NR 38
TC 22
Z9 23
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2010
VL 16
IS 14
BP 3786
EP 3794
DI 10.1158/1078-0432.CCR-10-0547
PG 9
WC Oncology
SC Oncology
GA 625NW
UT WOS:000279903100028
PM 20463088
ER
PT J
AU Vaishampayan, UN
Burger, AM
Sausville, EA
Heilbrun, LK
Li, J
Horiba, MN
Egorin, MJ
Ivy, P
Pacey, S
LoRusso, PM
AF Vaishampayan, Ulka N.
Burger, Angelika M.
Sausville, Edward A.
Heilbrun, Lance K.
Li, Jing
Horiba, M. Naomi
Egorin, Merrill J.
Ivy, Percy
Pacey, Simon
LoRusso, Patricia M.
TI Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of the
Combination of Sorafenib and Tanespimycin
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; SHOCK-PROTEIN 90; PHASE-II TRIAL; SOLID TUMORS;
MOLECULAR CHAPERONE; RESPONSE CRITERIA; MELANOMA MODELS; ANTITUMOR
AGENT; B-RAF; HSP90
AB Purpose: Heat shock protein (Hsp) 90 inhibition affects the Raf kinase signaling pathway and could enhance antitumor effects of sorafenib, a Raf kinase inhibitor. The combination of sorafenib and tanespimycin [17-allyl-amino-geldanamycin (17-AAG); NSC 330507/KOS-953] was evaluated in a phase I trial with the primary objective of defining a phase II dose.
Patients and Methods: The dose cohorts consisted of fixed continuous oral dosing of 400 mg sorafenib twice daily, starting at 14 days before tanespimycin, which was administered intravenously at escalating doses (starting at 300 mg/m, 2 with 50 mg/m(2) increments), on days 1, 8, and 15 in a 28-day cycle. Toxicity was assessed weekly, and response was evaluated every two cycles.
Results: Twenty-seven toxicity-evaluable patients were enrolled and treated at four dose levels. Predominant primary malignancies were renal cancer (12), melanoma (6), and colorectal cancer (4). Dose-limiting toxicities of grade 4 transaminitis and grade 3 hand-foot syndrome in one patient each were observed at 450 mg/m(2) of tanespimycin. One hundred fourteen cycles were administered with a median of four cycles (range 1-17 cycles). Plasma concentrations of sorafenib and metabolites reached steady state after 7 days. Tanespimycin did not alter sorafenib concentrations. Pharmacodynamics showed a decrease in Hsp90 levels and induction of Hsp70. Clinical efficacy was observed in 9 of 12 renal cancer patients and 4 of 6 melanoma patients
Conclusions: Recommended phase II doses of this combination are 400 mg sorafenib twice daily and 400 mg/m2 tanespimycin on days 1, 8, and 15, every 28 days. Clinical and pharmacodynamic activity was observed in kidney cancer and melanoma. Clin Cancer Res; 16(14); 3795-804. ((c))2010 AACR.
C1 [Vaishampayan, Ulka N.; Burger, Angelika M.; Li, Jing; LoRusso, Patricia M.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Med, Detroit, MI 48201 USA.
[Vaishampayan, Ulka N.; Burger, Angelika M.; Li, Jing; LoRusso, Patricia M.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Pharmacol, Detroit, MI 48201 USA.
[Heilbrun, Lance K.] Barbara Ann Karmanos Canc Inst, Biostat Unit, Detroit, MI USA.
[Sausville, Edward A.; Horiba, M. Naomi] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Egorin, Merrill J.] Univ Pittsburgh, Dept Med, Inst Canc, Pittsburgh, PA USA.
[Egorin, Merrill J.] Univ Pittsburgh, Dept Pharmacol, Inst Canc, Pittsburgh, PA 15261 USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program Branch, Bethesda, MD 20892 USA.
[Pacey, Simon] Royal Marsden Hosp, London SW3 6JJ, England.
RP Vaishampayan, UN (reprint author), Wayne State Univ, Karmanos Canc Inst, Hudson Webber Canc Res Ctr, 4th Floor,4100 John R, Detroit, MI 48201 USA.
EM vaishamu@karmanos.org
FU NIH [5UO1CA062487-14, UO1CA099168, 2MO1RR016500-006]; Cancer Center
[CA-22543]; National Cancer Institute Translational Research Initiative
[26XS162 (P6972)]
FX NIH grant 5UO1CA062487-14, NIH grant UO1CA099168, 2MO1RR016500-006, and
Cancer Center Support Grant CA-22543. Sorafenib/BAY43-9006 and
tanespimycin (17-AAG) were supplied by National Cancer Institute, Cancer
Therapy Evaluation Program, and correlatives were supported by the
National Cancer Institute Translational Research Initiative grant
26XS162 (P6972). The initial version of the protocol was designed in the
2004 ECCO-AACR-ASCO Workshop, "Methods in Clinical Cancer Research,"
Flims, Switzerland. M.J. Egorin is the recipient of an ASCO Cancer
Foundation Translational Research Professorship.
NR 34
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Z9 24
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2010
VL 16
IS 14
BP 3795
EP 3804
DI 10.1158/1078-0432.CCR-10-0503
PG 10
WC Oncology
SC Oncology
GA 625NW
UT WOS:000279903100029
PM 20525756
ER
PT J
AU Humblet, O
Williams, PL
Korrick, SA
Sergeyev, O
Emond, C
Birnbaum, LS
Burns, JS
Altshul, L
Patterson, DG
Turner, WE
Lee, MM
Revich, B
Hauser, R
AF Humblet, Olivier
Williams, Paige L.
Korrick, Susan A.
Sergeyev, Oleg
Emond, Claude
Birnbaum, Linda S.
Burns, Jane S.
Altshul, Larisa
Patterson, Donald G., Jr.
Turner, Wayman E.
Lee, Mary M.
Revich, Boris
Hauser, Russ
TI Predictors of Serum Dioxin, Furan, and PCB Concentrations among Women
from Chapaevsk, Russia
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS PCBS; AIR-FORCE VETERANS; DIBENZO-P-DIOXINS;
US POPULATION; BODY BURDEN; HUMAN-MILK; EXPOSURE; HEALTH;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; POLLUTION
AB Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs.
C1 [Humblet, Olivier; Korrick, Susan A.; Burns, Jane S.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Korrick, Susan A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Korrick, Susan A.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Sergeyev, Oleg] Samara State Med Univ, Dept Phys Educ & Hlth, Samara, Russia.
[Sergeyev, Oleg] Chapaevsk Med Assoc, Chapaevsk, Russia.
[Emond, Claude] Univ Montreal, Fac Med, Dept Environm & Occupat Hlth, Montreal, PQ H3C 3J7, Canada.
[Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIH, Natl Toxicol Program, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Altshul, Larisa] Environm Hlth & Engn Inc, Needham, MA USA.
[Patterson, Donald G., Jr.] EnviroSolut Consulting Inc, Jasper, GA USA.
[Turner, Wayman E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Pediat, Pediat Endocrinol Div, Worcester, MA USA.
[Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA.
[Revich, Boris] Russian Acad Sci, Ctr Demog & Human Ecol, Inst Forecasting, Moscow, Russia.
RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1405, Boston, MA 02115 USA.
EM rhauser@hohp.harvard.edu
RI Sergeyev, Oleg/H-8854-2013;
OI Sergeyev, Oleg/0000-0002-5745-3348; Lee, Mary/0000-0002-7204-4884
FU U.S. EPA [R82943701]; NIEHS [ES014370, ES00002, 5T32-ES07069-28];
NIEHS/NFIGRI [5T32ES016645-02]
FX We gratefully thank the study participants and the staff of the
Chapaevsk Medical Association. This work was funded by U.S. EPA grant
R82943701 and NIEHS grants ES014370, ES00002, and 5T32-ES07069-28. O.H.
is supported by 5T32ES016645-02 from NIEHS/NFIGRI. M.M.L. is a member of
the UMass DERC (DK32520). The research described in this article has
been reviewed by the National Institute of Environmental Health Sciences
and approved for publication. Approval does not signify that the
contents necessarily reflect the views of the Agency, nor does the
mention of trade names or commercial products constitute endorsement or
recommendation for use. The opinions expressed in this manuscript are
those of the authors and do not necessarily reflect the official opinion
of the Centers for Disease Control and Prevention. C.E. is an
International Consultant and the President of BioSimulation Consulting
Inc. L.A. is a consultant for Environmental Health and Engineering, Inc.
D.G.P. is a consultant for Axys Analytical Solutions, Fluid Management
Systems, Inc., and Trium Environmental Solutions. The other authors
declare they have no competing financial interest.
NR 33
TC 14
Z9 15
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD JUL 15
PY 2010
VL 44
IS 14
BP 5633
EP 5640
DI 10.1021/es100976j
PG 8
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 623NF
UT WOS:000279747100054
PM 20578718
ER
PT J
AU Silva, CM
Sato, S
Margolis, RN
AF Silva, Corinne M.
Sato, Sheryl
Margolis, Ronald N.
TI No time to lose: workshop on circadian rhythms and metabolic disease
SO GENES & DEVELOPMENT
LA English
DT News Item
DE Circadian; rhythms; metabolism; core clock; peripheral clocks
ID DORSOMEDIAL HYPOTHALAMIC NUCLEUS; SLEEP PHASE SYNDROME; PERIPHERAL
CLOCKS; EXPRESSION; PACEMAKER; REVEALS; PHOSPHORYLATION; CONSEQUENCES;
DEADENYLASE; COMPONENTS
AB The objective of the workshop was to gain a better understanding of the link between circadian rhythms and human health and disease. The impacts of circadian rhythms on metabolic gene regulation, as well as the effect of nutrient uptake and balance on the molecular components of the clock, were discussed. Topics included the neural circuitry underlying the central clock; the effect of the environment and diet on the central clock as well as peripheral, tissue-specific clocks; and the transcriptional, post-transcriptional, and post-translational (e. g., epigenomic) mechanisms through which these signals are transduced. Evidence presented during the meeting demonstrated that circadian rhythms and metabolism are intricately linked, and that disruption in these rhythms have profound consequences-many times leading to metabolic disease. The mechanisms by which circadian rhythms are maintained and the cross-talk with metabolic signaling are just beginning to be elucidated. However, the interactions between these fields and the knowledge learned will clearly have a profound impact on our understanding of metabolic disease and lead to novel therapeutic approaches in the future
C1 [Silva, Corinne M.; Sato, Sheryl; Margolis, Ronald N.] NIDDKD, Div Diabet Endocrinol & Metab Dis, Natl Inst Diabet, NIH, Bethesda, MD 20892 USA.
RP Silva, CM (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, Natl Inst Diabet, NIH, Bethesda, MD 20892 USA.
EM silvacm@mail.nih.gov
NR 52
TC 8
Z9 8
U1 1
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUL 15
PY 2010
VL 24
IS 14
BP 1456
EP 1464
DI 10.1101/gad.1948310
PG 9
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 626BS
UT WOS:000279941500002
PM 20634312
ER
PT J
AU Lim, J
Zhou, M
Veenstra, TD
Morrison, DK
AF Lim, Junghwa
Zhou, Ming
Veenstra, Timothy D.
Morrison, Deborah K.
TI The CNK1 scaffold binds cytohesins and promotes insulin pathway
signaling
SO GENES & DEVELOPMENT
LA English
DT Article
DE Protein scaffold; signal transduction; insulin pathway
ID NUCLEOTIDE EXCHANGE FACTORS; DOMAIN-CONTAINING PROTEIN; MEMBRANE
GLYCOPROTEIN PC-1; BREAST-CANCER CELLS; RAF ACTIVATION; RECEPTOR;
DROSOPHILA; FAMILY; TRANSDUCTION; DOWNSTREAM
AB Protein scaffolds play an important role in signal transduction, regulating the localization of signaling components and mediating key protein interactions. Here, we report that the major binding partners of the Connector Enhancer of KSR 1 (CNK1) scaffold are members of the cytohesin family of Arf guanine nucleotide exchange factors, and that the CNK1 cytohesin interaction is critical for activation of the PI3K/AKT cascade downstream from insulin and insulin-like growth factor 1 (IGF-1) receptors. We identified a domain located in the C-terminal region of CNK1 that interacts constitutively with the coiled-coil domain of the cytohesins, and found that CNK1 facilitates the membrane recruitment of cytohesin-2 following insulin stimulation. Moreover, through protein depletion and rescue experiments, we found that the CNK1 cytohesin interaction promotes signaling from plasma membrane-bound Arf GTPases to the phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) to generate a PIP(2)-rich microenvironment that is critical for the membrane recruitment of insulin receptor substrate 1 (IRS1) and signal transmission to the PI3K/AKT cascade. These findings identify CNK1 as a new positive regulator of insulin signaling.
C1 [Lim, Junghwa; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Zhou, Ming; Veenstra, Timothy D.] SAIC, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, DHHS
[N01-CO-1240]
FX We thank Dan Ritt and Suzanne Specht for excellent technical assistance,
and members of the Laboratory of Cell and Developmental Signaling for
helpful discussions and comments. This project was supported with
federal funds from the National Cancer Institute, National Institutes of
Health, DHHS, in part under contract N01-CO-1240.
NR 40
TC 39
Z9 39
U1 1
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUL 15
PY 2010
VL 24
IS 14
BP 1496
EP 1506
DI 10.1101/gad.1904610
PG 11
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 626BS
UT WOS:000279941500007
PM 20634316
ER
PT J
AU Acuna-Alonzo, V
Flores-Dorantes, T
Kruit, JK
Villarreal-Molina, T
Arellano-Campos, O
Hunemeier, T
Moreno-Estrada, A
Ortiz-Lopez, MG
Villamil-Ramirez, H
Leon-Mimila, P
Villalobos-Comparan, M
Jacobo-Albavera, L
Ramirez-Jimenez, S
Sikora, M
Zhang, LH
Pape, TD
Granados-Silvestre, MD
Montufar-Robles, I
Tito-Alvarez, AM
Zurita-Salinas, C
Bustos-Arriaga, J
Cedillo-Barron, L
Gomez-Trejo, C
Barquera-Lozano, R
Vieira, JP
Granados, J
Romero-Hidalgo, S
Huertas-Vazquez, A
Gonzalez-Martin, A
Gorostiza, A
Bonatto, SL
Rodriguez-Cruz, M
Wang, L
Tusie-Luna, T
Aguilar-Salinas, CA
Lisker, R
Moises, RS
Menjivar, M
Salzano, FM
Knowler, WC
Bortolini, MC
Hayden, MR
Baier, LJ
Canizales-Quinteros, S
AF Acuna-Alonzo, Victor
Flores-Dorantes, Teresa
Kruit, Janine K.
Villarreal-Molina, Teresa
Arellano-Campos, Olimpia
Huenemeier, Tabita
Moreno-Estrada, Andres
Guadalupe Ortiz-Lopez, Ma
Villamil-Ramirez, Hugo
Leon-Mimila, Paola
Villalobos-Comparan, Marisela
Jacobo-Albavera, Leonor
Ramirez-Jimenez, Salvador
Sikora, Martin
Zhang, Lin-Hua
Pape, Terry D.
de Angeles Granados-Silvestre, Ma
Montufar-Robles, Isela
Tito-Alvarez, Ana M.
Zurita-Salinas, Camilo
Bustos-Arriaga, Jose
Cedillo-Barron, Leticia
Gomez-Trejo, Celta
Barquera-Lozano, Rodrigo
Vieira-Filho, Joao P.
Granados, Julio
Romero-Hidalgo, Sandra
Huertas-Vazquez, Adriana
Gonzalez-Martin, Antonio
Gorostiza, Amaya
Bonatto, Sandro L.
Rodriguez-Cruz, Maricela
Wang, Li
Tusie-Luna, Teresa
Aguilar-Salinas, Carlos A.
Lisker, Ruben
Moises, Regina S.
Menjivar, Marta
Salzano, Francisco M.
Knowler, William C.
Catira Bortolini, M.
Hayden, Michael R.
Baier, Leslie J.
Canizales-Quinteros, Samuel
TI A functional ABCA1 gene variant is associated with low HDL-cholesterol
levels and shows evidence of positive selection in Native Americans
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID OBESITY-RELATED COMORBIDITIES; PIMA-INDIANS; MEXICAN POPULATION;
DIABETES-MELLITUS; HEPATIC STEATOSIS; R230C VARIANT; DISEASE; GENOME;
PLASMA; PREVALENCE
AB It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P < 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.
C1 [Acuna-Alonzo, Victor; Flores-Dorantes, Teresa; Villarreal-Molina, Teresa; Villamil-Ramirez, Hugo; Leon-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramirez-Jimenez, Salvador; Tusie-Luna, Teresa; Canizales-Quinteros, Samuel] Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Biol Mol & Med Genom, Mexico City 14000, DF, Mexico.
[Arellano-Campos, Olimpia; Aguilar-Salinas, Carlos A.] INCMNSZ, Dept Endocrinol & Metab, Mexico City 14000, DF, Mexico.
[Granados, Julio] INCMNSZ, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico.
[Lisker, Ruben] INCMNSZ, Direct Res, Mexico City 14000, DF, Mexico.
[Acuna-Alonzo, Victor; Gomez-Trejo, Celta; Barquera-Lozano, Rodrigo; Gorostiza, Amaya] ENAH, Mol Genet Lab, Mexico City 14030, DF, Mexico.
[Kruit, Janine K.; Zhang, Lin-Hua; Pape, Terry D.; Hayden, Michael R.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z4, Canada.
[Huenemeier, Tabita; Salzano, Francisco M.; Catira Bortolini, M.] Univ Fed Rio Grande do Sul, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil.
[Moreno-Estrada, Andres] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Guadalupe Ortiz-Lopez, Ma; de Angeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Menjivar, Marta] Univ Nacl Autonoma Mexico, Fac Chem, Dept Biol, Mexico City 04510, DF, Mexico.
[Guadalupe Ortiz-Lopez, Ma; de Angeles Granados-Silvestre, Ma; Montufar-Robles, Isela] Hosp Juarez Mexico, Mol Endocrinol Lab, Mexico City, DF, Mexico.
[Sikora, Martin] CEXS UPF PRBB, UPF CSIC, Inst Evolutionary Biol, Barcelona 374908003, Spain.
[Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo] Labs Zurita & Zurita, N-12120 Quito, Ecuador.
[Bustos-Arriaga, Jose; Cedillo-Barron, Leticia] IPN, CINVESTAV, Dept Mol Biomed, Mexico City 07360, DF, Mexico.
[Vieira-Filho, Joao P.; Moises, Regina S.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, BR-04034970 Sao Paulo, Brazil.
[Romero-Hidalgo, Sandra] Inst Nacl Med Genom, Dept Computat Genom, Mexico City 01900, DF, Mexico.
[Huertas-Vazquez, Adriana] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
[Gonzalez-Martin, Antonio; Gorostiza, Amaya] Univ Complutense Madrid, Fac Biol, Dept Zool & Phys Anthropol, E-28040 Madrid, Spain.
[Bonatto, Sandro L.] Pontificia Univ Catolica Rio Grande do Sul, Fac Biol Sci, BR-90619900 Porto Alegre, RS, Brazil.
[Rodriguez-Cruz, Maricela] Mexican Inst Social Secur, Natl Med Ctr 21 Century, Pediat Hosp, Unit Med Res Nutr, Mexico City 06725, DF, Mexico.
[Wang, Li] Chinese Acad Sci, Inst Genet & Dev Biol, Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China.
[Knowler, William C.; Baier, Leslie J.] NIDDK, NIH, Phoenix, AZ 85014 USA.
RP Canizales-Quinteros, S (reprint author), Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Biol Mol & Med Genom, 15 Colonia Secc 16, Mexico City 14000, DF, Mexico.
EM cani@servidor.unam.mx
RI Arellano, Olimpia/A-8497-2012; Acuna Alonzo, Victor/E-2312-2013; Lisker,
Ruben/N-3094-2013; Gonzalez-Martin, Antonio/A-5489-2015; Sikora,
Martin/C-8609-2015; Salzano, Francisco/L-7916-2015; Hayden,
Michael/D-8581-2011; Bonatto, Sandro/A-1240-2010; Evolution and
Conservation Biology, UCM Group /K-9382-2014
OI Acuna Alonzo, Victor/0000-0003-2205-7625; Lisker,
Ruben/0000-0003-4272-5766; Gonzalez-Martin, Antonio/0000-0003-0276-0778;
Sikora, Martin/0000-0003-2818-8319; Hayden, Michael/0000-0001-5159-1419;
Bonatto, Sandro/0000-0002-0064-467X;
FU Consejo Nacional de Ciencia y Tecnologia (CONACYT) Mexico [69856];
Fundacion Mexicana para la Salud-Silanes [660]; National Institute of
Digestive and Kidney Diseases (NIDDK), NIH; Canadian Institutes of
Health Research (CIHR); Michael Smith Foundation for Health Research
(MSFHR)
FX This research was supported by grant 69856 from the Consejo Nacional de
Ciencia y Tecnologia (CONACYT) Mexico, and partly supported by grant 660
from the Fundacion Mexicana para la Salud-Silanes; by the Intramural
Research Program of the National Institute of Digestive and Kidney
Diseases (NIDDK), NIH; and by a grant of the Canadian Institutes of
Health Research (CIHR). V. A.-A., T.F.-D., M. V.-C. and L.J.-A. were
supported by fellowships from CONACYT, Mexico. J.K.K. was supported by
fellowships of the Michael Smith Foundation for Health Research (MSFHR)
and the CIHR. M. R. H. holds a Canada Research Chair in Human Genetics.
NR 54
TC 48
Z9 51
U1 1
U2 21
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 JUL 15
PY 2010
VL 19
IS 14
BP 2877
EP 2885
DI 10.1093/hmg/ddq173
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 619ZP
UT WOS:000279469100012
PM 20418488
ER
PT J
AU Wang, XS
Pankratz, VS
Fredericksen, Z
Tarrell, R
Karaus, M
McGuffog, L
Pharaoh, PD
Ponder, BA
Dunning, AM
Peock, S
Cook, M
Oliver, C
Frost, D
Sinilnikova, OM
Stoppa-Lyonnet, D
Mazoyer, S
Houdayer, C
Hogervorst, FBL
Hooning, MJ
Ligtenberg, MJ
Spurdle, A
Chenevix-Trench, G
Schmutzler, RK
Wappenschmidt, B
Engel, C
Meindl, A
Domchek, SM
Nathanson, KL
Rebbeck, TR
Singer, CF
Gschwantler-Kaulich, D
Dressler, C
Fink, A
Szabo, CI
Zikan, M
Foretova, L
Claes, K
Thomas, G
Hoover, RN
Hunter, DJ
Chanock, SJ
Easton, DF
Antoniou, AC
Couch, FJ
AF Wang, Xianshu
Pankratz, V. Shane
Fredericksen, Zachary
Tarrell, Robert
Karaus, Mary
McGuffog, Lesley
Pharaoh, Paul D. P.
Ponder, Bruce A. J.
Dunning, Alison M.
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Sinilnikova, Olga M.
Stoppa-Lyonnet, Dominique
Mazoyer, Sylvie
Houdayer, Claude
Hogervorst, Frans B. L.
Hooning, Maartje J.
Ligtenberg, Marjolijn J.
Spurdle, Amanda
Chenevix-Trench, Georgia
Schmutzler, Rita K.
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy R.
Singer, Christian F.
Gschwantler-Kaulich, Daphne
Dressler, Catherina
Fink, Anneliese
Szabo, Csilla I.
Zikan, Michal
Foretova, Lenka
Claes, Kathleen
Thomas, Gilles
Hoover, Robert N.
Hunter, David J.
Chanock, Stephen J.
Easton, Douglas F.
Antoniou, Antonis C.
Couch, Fergus J.
CA EMBRACE
GEMO
HEBON
kCon Fab
TI Common variants associated with breast cancer in genome-wide association
studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation
carriers
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ESTROGEN-RECEPTOR; CONFER SUSCEPTIBILITY; GENETIC-VARIATION; ALLELES;
PREDISPOSITION; INVESTIGATORS; POLYMORPHISM; CONSORTIUM; COMPLEX; MODEL
AB Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 x 10(-3)) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutation carriers from nine centers. Associations with breast cancer risk were assessed using Cox models weighted for penetrance. Eight SNPs in BRCA1 carriers and 12 SNPs in BRCA2 carriers, representing an enrichment over the number expected, were significantly associated with breast cancer risk (P(trend) < 0.01). The minor alleles of rs6138178 in SNRPB and rs6602595 in CAMK1D displayed the strongest associations in BRCA1 carriers (HR = 0.78, 95% CI: 0.69-0.90, P(trend) = 3.6 x 10(-4) and HR = 1.25, 95% CI: 1.10-1.41, P(trend) = 4.2 x 10(-4)), whereas rs9393597 in LOC134997 and rs12652447 in FBXL7 showed the strongest associations in BRCA2 carriers (HR = 1.55, 95% CI: 1.25-1.92, P(trend) = 6 x 10(-5) and HR = 1.37, 95% CI: 1.16-1.62, P(trend) = 1.7 x 10(-4)). The magnitude and direction of the associations were consistent with the original GWAS. In subsequent risk assessment studies, the loci appeared to interact multiplicatively for breast cancer risk in BRCA1 and BRCA2 carriers. Promising candidate SNPs from GWAS were identified as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. Upon further validation, these SNPs together with other genetic and environmental factors may improve breast cancer risk assessment in these populations.
C1 [Couch, Fergus J.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[McGuffog, Lesley; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.
[Pharaoh, Paul D. P.; Ponder, Bruce A. J.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France.
[Stoppa-Lyonnet, Dominique; Houdayer, Claude; GEMO] Univ Paris 05, Inst Curie, Serv Genet Oncol, INSERM U509, Paris, France.
[Mazoyer, Sylvie] Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France.
[Hogervorst, Frans B. L.; HEBON] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands.
[Hooning, Maartje J.] Rotterdam Family Canc Clin, Dept Med Oncol, Erasmus, Netherlands.
[Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Spurdle, Amanda; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[kCon Fab] Peter MacCallum Canc Inst, KConFab Kathleen Cunningham Fdn Consortium Res Fa, Melbourne, Vic 3002, Australia.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
[Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, D-8000 Munich, Germany.
[Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Philadelphia, PA 19104 USA.
[Singer, Christian F.; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese] Med Univ Vienna, Vienna, Austria.
[Zikan, Michal] Charles Univ Prague, Fac Med 1, Dept Biochem & Expt Oncol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Thomas, Gilles; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hunter, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Chanock, Stephen J.] NCI, Adv Technol Ctr, Gaithersburg, MD USA.
RP Couch, FJ (reprint author), Mayo Clin, Coll Med, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA.
EM couch.fergus@mayo.edu
RI Spurdle, Amanda/A-4978-2011; Hoogerbrugge, Nicoline/O-1016-2013;
GLADIEFF, Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013;
OI Spurdle, Amanda/0000-0003-1337-7897; GLADIEFF,
Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474;
Eeles, Rosalind/0000-0002-3698-6241; Nathanson,
Katherine/0000-0002-6740-0901; Dunning, Alison
Margaret/0000-0001-6651-7166; Evans, Gareth/0000-0002-8482-5784
FU Cancer Research UK [11174, C1287/A10118, C1287/A8874, C5047/A8385,
A10123, 10118]; Intramural NIH HHS; NCI NIH HHS [P50 CA116201, R01
CA122340, R01 CA128978]
NR 29
TC 38
Z9 39
U1 4
U2 9
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 JUL 15
PY 2010
VL 19
IS 14
BP 2886
EP 2897
DI 10.1093/hmg/ddq174
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 619ZP
UT WOS:000279469100013
PM 20418484
ER
PT J
AU Lindor, NM
Rabe, KG
Petersen, GM
Chen, H
Bapat, B
Hopper, J
Young, J
Jenkins, M
Potter, J
Newcomb, P
Templeton, A
LeMarchand, L
Grove, J
Burgio, MR
Haile, R
Green, J
Woods, MO
Seminara, D
Limburg, PJ
Thibodeau, SN
AF Lindor, Noralane M.
Rabe, Karl G.
Petersen, Gloria M.
Chen, Helen
Bapat, Bharati
Hopper, John
Young, Joanne
Jenkins, Mark
Potter, John
Newcomb, Polly
Templeton, Allyson
LeMarchand, Loic
Grove, John
Burgio, Michael R.
Haile, Robert
Green, Jane
Woods, Michael O.
Seminara, Daniela
Limburg, Paul J.
Thibodeau, Stephen N.
TI Parent of origin effects on age at colorectal cancer diagnosis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE imprinting; gender; pseudoautosomal; X-linked
ID TURNER-SYNDROME; IMPRINTED GENES; IDENTIFICATION; STRATEGIES; PHENOTYPE;
CRITERIA; RISK
AB Genomic imprinting refers to a parent-of-origin specific effect on gene expression. At least 1% of genes in the human genome are modulated in this manner. We sought evidence for genomic imprinting in colorectal cancer by studying the ages at diagnosis in the offspring of 2,061 parent-child pairs in which both parent and child were affected by nonsyndromic colorectal cancer. Families were ascertained through the colon Cancer Family Registry [http://epi.grants.cancer.gov/CFR/ http://epi.grants.cancer.gov/CFR/] from both population-based and clinic-based sources. We found that the affected offspring of affected fathers were on average younger than offspring of affected mothers (55.8 vs. 53.7 years; p = 0.0003), but when divided into sons and daughters, this difference was driven entirely by younger age at diagnosis in daughters of affected fathers compared to sons (52.3 years vs. 55.1 years; p = 0.0004). A younger age at diagnosis in affected daughters of affected fathers was also observable in various subsets including families that met Amsterdam II Criteria, families that did not meet Amsterdam Criteria, and in families with documented normal DNA mismatch repair in tumors. Imprinting effects are not expected to be affected by the sex of the offspring. Possible explanations for these unexpected findings include: an imprinted gene on the pseudoautosomal regions of the X chromosome; (0 an imprinted autosomal gene that affects a sex-specific pathway; or (iii) an X-linked gene unmasked because of colonic tissue-specific preferential inactivation of the maternal X chromosome.
C1 [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA.
[Rabe, Karl G.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Petersen, Gloria M.] Mayo Clin, Div Epidemiol, Rochester, MN USA.
[Chen, Helen] Mayo Clin, Dept Hlth Sci Res Res Comp Facil, Rochester, MN USA.
[Bapat, Bharati] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Hopper, John; Jenkins, Mark] Univ Melbourne, Melbourne, Vic, Australia.
[Young, Joanne] Queensland Inst Med Res, Familial Canc Lab, Brisbane, Qld 4006, Australia.
[Potter, John; Newcomb, Polly; Templeton, Allyson] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[LeMarchand, Loic; Grove, John] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Burgio, Michael R.] Sci Consulting Grp Inc, Gaithersburg, MD USA.
[Haile, Robert] Univ So Calif, Human Canc Genet Program, Los Angeles, CA USA.
[Green, Jane; Woods, Michael O.] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada.
[Seminara, Daniela] NCI, Dept Canc Biol, Div Canc Control & Populat Sci, Clin & Genet Epidemiol Res Branch,NIH, Bethesda, MD 20892 USA.
[Limburg, Paul J.] Mayo Clin, Div Gastroenterol, Rochester, MN USA.
[Thibodeau, Stephen N.] Mayo Clin, Div Lab Genet, Rochester, MN USA.
RP Lindor, NM (reprint author), Mayo Fdn, E7B, Rochester, MN 55905 USA.
EM nlindor@mayo.edu
RI Bapat, Bharati/B-5839-2014; Jenkins, Mark/P-7803-2015
OI Potter, John/0000-0001-5439-1500; Jenkins, Mark/0000-0002-8964-6160
FU National Cancer Institute, National Institutes of Health [CA-95-011];
Australian Colorectal Cancer Family Registry [UO1 CA097735]; USC
Familial Colorectal Neoplasia Collaborative Group [UO1 CA074799]; Mayo
Clinic Cooperative Family Registry for Colon Cancer Studies [UO1
CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer
[UO1 CA074783]; Seattle Colorectal Cancer Family Registry [UO1
CA074794]; University of Hawaii Colorectal Cancer Family Registry [UO1
CA074806]; University of California, Irvine Informatics Center [UO1
CA078296]
FX Grant sponsor: National Cancer Institute, National Institutes of Health;
Grant number: RFA #CA-95-011; Grant sponsor: Australian Colorectal
Cancer Family Registry; Grant number: UO1 CA097735; Grant sponsor: USC
Familial Colorectal Neoplasia Collaborative Group; Grant number: UO1
CA074799; Grant sponsor: Mayo Clinic Cooperative Family Registry for
Colon Cancer Studies; Grant number: UO1 CA074800; Grant sponsor: Ontario
Registry for Studies of Familial Colorectal Cancer; Grant number: UO1
CA074783; Grant sponsor: Seattle Colorectal Cancer Family Registry;
Grant number: UO1 CA074794; Grant sponsor: University of Hawaii
Colorectal Cancer Family Registry; Grant number: UO1 CA074806; Grant
sponsor: University of California, Irvine Informatics Center; Grant
number: UO1 CA078296
NR 19
TC 4
Z9 4
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2010
VL 127
IS 2
BP 361
EP 366
DI 10.1002/ijc.25037
PG 6
WC Oncology
SC Oncology
GA 612RC
UT WOS:000278919000012
PM 19904757
ER
PT J
AU Shiba, Y
Romer, W
Mardones, GA
Burgos, PV
Lamaze, C
Johannes, L
AF Shiba, Yoko
Roemer, Winfried
Mardones, Gonzalo A.
Burgos, Patricia V.
Lamaze, Christophe
Johannes, Ludger
TI AGAP2 regulates retrograde transport between early endosomes and the TGN
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Shiga toxin; Arf; ArfGAP; ARAP; Mannose 6-phosphate receptor; TGN46;
Cholera toxin; Clathrin; Retromer; VSVG; Transferrin
ID MANNOSE 6-PHOSPHATE RECEPTORS; GTPASE-ACTIVATING PROTEIN; TO-GOLGI
TRANSPORT; TOXIN B-SUBUNIT; SHIGA-TOXIN; COPI VESICLES; EARLY/RECYCLING
ENDOSOMES; INTRACELLULAR MOVEMENT; CELL-SURFACE; ARF GAPS
AB The retrograde transport route links early endosomes and the TGN. Several endogenous and exogenous cargo proteins use this pathway, one of which is the well-explored bacterial Shiga toxin. ADP-ribosylation factors (Arfs) are similar to 20 kDa GTP-binding proteins that are required for protein traffic at the level of the Golgi complex and early endosomes. In this study, we expressed mutants and protein fragments that bind to Arf-GTP to show that Arf1, but not Arf6 is required for transport of Shiga toxin from early endosomes to the TGN. We depleted six Arf1-specific ARF-GTPase-activating proteins and identified AGAP2 as a crucial regulator of retrograde transport for Shiga toxin, cholera toxin and the endogenous proteins TGN46 and mannose 6-phosphate receptor. In AGAP2-depleted cells, Shiga toxin accumulates in transferrin-receptor-positive early endosomes, suggesting that AGAP2 functions in the very early steps of retrograde sorting. A number of other intracellular trafficking pathways are not affected under these conditions. These results establish that Arf1 and AGAP2 have key trafficking functions at the interface between early endosomes and the TGN.
C1 [Shiba, Yoko; Roemer, Winfried; Lamaze, Christophe; Johannes, Ludger] Inst Curie, Ctr Rech, Traff Signaling & Delivery Lab, F-75248 Paris 05, France.
[Shiba, Yoko; Roemer, Winfried; Lamaze, Christophe; Johannes, Ludger] CNRS, UMR144, F-75700 Paris, France.
[Mardones, Gonzalo A.; Burgos, Patricia V.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Mardones, Gonzalo A.; Burgos, Patricia V.] Univ Austral Chile, Dept Physiol, Valdivia 5099200, Chile.
RP Johannes, L (reprint author), Inst Curie, Ctr Rech, Traff Signaling & Delivery Lab, 26 Rue Ulm, F-75248 Paris 05, France.
EM johannes@curie.fr
FU Association pour la Recherche Contre le Cancer [3143]; Agence Nationale
pour la Recherche; NICHD (NIH); Association pour la Recherche sur le
Cancer
FX We would like to thank Philippe Chavrier, Kazuhisa Nakayama, Jean
Salamero, and Franck Perez, Michel Bornens, and Paul Randazzo for
reagents. The work was supported by grants from Association pour la
Recherche Contre le Cancer (3143) and Agence Nationale pour la Recherche
(Programme blanc), the intramural program of NICHD (NIH), and by a
fellowship from Association pour la Recherche sur le Cancer to Y.S.
Deposited in PMC for release after 12 months.
NR 59
TC 11
Z9 11
U1 1
U2 8
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUL 15
PY 2010
VL 123
IS 14
BP 2381
EP 2390
DI 10.1242/jcs.057778
PG 10
WC Cell Biology
SC Cell Biology
GA 629BE
UT WOS:000280168200005
PM 20551179
ER
PT J
AU Santiago, ML
Benitez, RL
Montano, M
Hasenkrug, KJ
Greene, WC
AF Santiago, Mario L.
Benitez, Robert L.
Montano, Mauricio
Hasenkrug, Kim J.
Greene, Warner C.
TI Innate Retroviral Restriction by Apobec3 Promotes Antibody Affinity
Maturation In Vivo
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID B-CELL ACTIVATION; MURINE LEUKEMIA-VIRUS; FRIEND-VIRUS; VIF PROTEIN;
HIV-1 VIF; ANTIVIRAL ACTIVITY; IMMUNE-RESPONSES; GERMINAL-CENTERS;
RESISTANCE GENE; ENZYME APOBEC3G
AB Apobec3/Rfv3 is an innate immune factor that promotes the neutralizing Ab response against Friend retrovirus (FV) in infected mice. Based on its evolutionary relationship to activation-induced deaminase, Apobec3 might directly influence Ab class switching and affinity maturation independently of viral infection. Alternatively, the antiviral activity of Apobec3 may indirectly influence neutralizing Ab responses by reducing early FV-induced pathology in critical immune compartments. To distinguish between these possibilities, we immunized wild-type and Apobec3-deficient C57BL/6 (B6) mice with (4-hydroxy-3-nitrophenyl) acetyl (NP) hapten and evaluated the binding affinity of the resultant NP-specific Abs. These studies revealed similar affinity maturation of NP-specific IgG1 Abs between wild-type and Apobec3-deficient mice in the absence of FV infection. In contrast, hapten-specific Ab affinity maturation was significantly compromised in Apobec3-deficient mice infected with FV. In highly susceptible (B6 x A.BY) F-1 mice, the B6 Apobec3 gene protected multiple cell types in the bone marrow and spleen from acute FV infection, including erythroid, B, T, and myeloid cells. In addition, B6 Apobec3 deficiency was associated with elevated Ig levels, but decreased induction of splenic germinal center B cells and plasmablasts during acute FV infection. These data suggest that Apobec3 indirectly influences FV-specific neutralizing Ab responses by reducing virus-induced immune dysfunction. These findings raise the possibility that enabling Apobec3 activity during acute infection with human pathogenic retroviruses, such as HIV-1, may similarly facilitate stronger virus-specific neutralizing Ab responses. The Journal of Immunology, 2010, 185: 1114-1123.
C1 [Santiago, Mario L.] Univ Colorado Denver, Div Infect Dis, Aurora, CO 80045 USA.
[Santiago, Mario L.] Univ Colorado Denver, Dept Microbiol, Aurora, CO 80045 USA.
[Santiago, Mario L.] Univ Colorado Denver, Integrated Dept Immunol, Aurora, CO 80045 USA.
[Greene, Warner C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
[Greene, Warner C.] Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94158 USA.
[Greene, Warner C.] Univ Calif San Francisco, Dept Immunol, San Francisco, CA 94158 USA.
[Benitez, Robert L.; Montano, Mauricio; Greene, Warner C.] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Santiago, ML (reprint author), Univ Colorado Denver, Div Infect Dis, Mail Stop B168,12700 E 19th Ave, Aurora, CO 80045 USA.
EM mario.santiago@ucdenver.edu
OI Santiago, Mario L./0000-0001-7792-2706
FU National Institutes of Health [R56 AI-0841230, R01 A065329]
FX This work was supported by National Institutes of Health Grants R56
AI-0841230 (to M. L. S.) and R01 A065329 (to W. C. G.).
NR 61
TC 19
Z9 19
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2010
VL 185
IS 2
BP 1114
EP 1123
DI 10.4049/jimmunol.1001143
PG 10
WC Immunology
SC Immunology
GA 622PH
UT WOS:000279675200039
PM 20566830
ER
PT J
AU Cardenas, I
Means, RE
Aldo, P
Koga, K
Lang, SM
Booth, C
Manzur, A
Oyarzun, E
Romero, R
Mor, G
AF Cardenas, Ingrid
Means, Robert E.
Aldo, Paulomi
Koga, Kaori
Lang, Sabine M.
Booth, Carmen
Manzur, Alejandro
Oyarzun, Enrique
Romero, Roberto
Mor, Gil
TI Viral Infection of the Placenta Leads to Fetal Inflammation and
Sensitization to Bacterial Products Predisposing to Preterm Labor
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTOR-3; MURINE GAMMAHERPESVIRUS 68; HERPES-SIMPLEX-VIRUS;
DOUBLE-STRANDED-RNA; INFLUENZA-A VIRUS; NF-KAPPA-B; INTRAUTERINE
INFECTION; TROPHOBLAST RESPONSES; ADENOASSOCIATED VIRUS; IN-VIVO
AB Pandemics pose a more significant threat to pregnant women than to the nonpregnant population and may have a detrimental effect on the well being of the fetus. We have developed an animal model to evaluate the consequences of a viral infection characterized by lack of fetal transmission. The experiments described in this work show that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental deficiencies. Furthermore, we demonstrate that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labor. It is critical to take into consideration the fact that during pregnancy it is not only the maternal immune system responding, but also the fetal/placental unit. Our results further support the immunological role of the placenta and the fetus affecting the global response of the mother to microbial infections. This is relevant for making decisions associated with treatment and prevention during pandemics. The Journal of Immunology, 2010, 185: 1248-1257.
C1 [Mor, Gil] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA.
[Means, Robert E.; Lang, Sabine M.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Booth, Carmen] Yale Univ, Sch Med, Dept Comparat Med, New Haven, CT 06520 USA.
[Manzur, Alejandro; Oyarzun, Enrique] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
[Romero, Roberto] Eunice Kennedy Shriver NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48201 USA.
RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,LSOG 305A, New Haven, CT 06520 USA.
EM gil.mor@yale.edu
FU National Institutes of Health [NICDH P01HD054713, 3N01 HD23342]; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX This work was in part supported by grants from the National Institutes
of Health (NICDH P01HD054713 and 3N01 HD23342) and the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health,
Department of Health and Human Services.
NR 84
TC 78
Z9 79
U1 1
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2010
VL 185
IS 2
BP 1248
EP 1257
DI 10.4049/jimmunol.1000289
PG 10
WC Immunology
SC Immunology
GA 622PH
UT WOS:000279675200054
PM 20554966
ER
PT J
AU Martin, JF
Perry, JSA
Jakhete, NR
Wang, X
Bielekova, B
AF Martin, Jayne F.
Perry, Justin S. A.
Jakhete, Neha R.
Wang, Xiang
Bielekova, Bibiana
TI An IL-2 Paradox: Blocking CD25 on T Cells Induces IL-2-Driven Activation
of CD56(bright) NK Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; REMITTING MULTIPLE-SCLEROSIS;
RECEPTOR-ALPHA-CHAIN; PERIPHERAL-BLOOD; INTERFERON-BETA; IN-VIVO;
DACLIZUMAB; EXPRESSION; ANTIBODY; DISEASE
AB Daclizumab (Dac), an Ab against the IL-2R alpha-chain, inhibits brain inflammation in patients with multiple sclerosis, while expanding CD56(bright) immunoregulatory NK cells in vivo. We hypothesized that this unexpected expansion is paradoxically IL-2 driven; caused by the increased availability of T cell-derived IL-2 for NK cell signaling. To this end, we performed ex vivo functional analyses of CD56(bright) NK cells and T cells from patients in clinical trials with Dac. We developed in vitro models to investigate mechanisms for ex vivo observations. We observed that Dac treatment caused decreased numbers and proliferation of FoxP3(+) T regulatory cells (Tregs), a model T cell population known to be dependent on IL-2 for proliferation and survival. As anticipated, Dac therapy inhibited IL-2 signaling in all T cells; however, we also observed functional adaptation of T cells to low IL-2 signal in vivo, characterized by the concomitant enhancement of IL-7 signaling on all T cells and parallel increase of CD127 expression by Tregs. In contrast, IL-2 signaling on CD56(bright) NK cells was not inhibited by Dac and their in vivo proliferation and cytotoxicity actually increased. Mechanistic studies indicated that the activation of CD56(bright) NK cells was likely IL-2 driven, as low doses of IL-2, but not IL-15, mimicked this activation in vitro. Our study provides insight into the role that IL-2 and CD25 play in functional regulation of two important immunoregulatory cell populations in humans: FoxP3(+) Tregs and CD56(bright) NK cells. The Journal of Immunology, 2010, 185: 1311-1320.
C1 [Martin, Jayne F.; Perry, Justin S. A.; Jakhete, Neha R.; Wang, Xiang; Bielekova, Bibiana] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5C103,10 Ctr Dr,MSC1400, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
FU National Institutes of Health, National Institute for Neurological
Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute for Neurological
Disorders and Stroke.
NR 31
TC 65
Z9 67
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2010
VL 185
IS 2
BP 1311
EP 1320
DI 10.4049/jimmunol.0902238
PG 10
WC Immunology
SC Immunology
GA 622PH
UT WOS:000279675200061
PM 20543101
ER
PT J
AU Crain, MJ
Chernoff, MC
Oleske, JM
Brogly, SB
Malee, KM
Borum, PR
Meyer, WA
Mitchell, WG
Moye, JH
Ford-Chatterton, HM
Van Dyke, RB
Seage, GR
AF Crain, Marilyn J.
Chernoff, Miriam C.
Oleske, James M.
Brogly, Susan B.
Malee, Kathleen M.
Borum, Peggy R.
Meyer, William A., III
Mitchell, Wendy G.
Moye, John H.
Ford-Chatterton, Heather M.
Van Dyke, Russell B.
Seage, George R., III
TI Possible Mitochondrial Dysfunction and Its Association with
Antiretroviral Therapy Use in Children Perinatally Infected with HIV
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID REVERSE-TRANSCRIPTASE INHIBITORS; BLOOD MONONUCLEAR-CELLS;
RESPIRATORY-CHAIN DISORDERS; NUCLEOSIDE ANALOGS; CLINICAL-TRIALS;
UNINFECTED CHILDREN; PEDIATRIC-PATIENTS; LACTIC-ACIDOSIS; MTDNA LEVELS;
DNA LEVELS
AB Background. Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection.
Methods. Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquete Perinatale Francaise criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression.
Results. Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction.
Conclusions. Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.
C1 [Crain, Marilyn J.] Univ Alabama, Sch Med, Birmingham, AL USA.
[Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chernoff, Miriam C.; Brogly, Susan B.; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Oleske, James M.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Malee, Kathleen M.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Borum, Peggy R.] Univ Florida, Gainesville, FL USA.
[Meyer, William A., III] Quest Diagnost, Baltimore, MD USA.
[Moye, John H.] NICHHD, Bethesda, MD 20892 USA.
[Mitchell, Wendy G.] Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Los Angeles, CA USA.
[Ford-Chatterton, Heather M.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Van Dyke, Russell B.] Tulane Univ, New Orleans, LA 70118 USA.
RP Crain, MJ (reprint author), UAB, Sch Med, 1600 7th Ave S,306A CHB, Birmingham, AL 35233 USA.
EM mcrain@peds.uab.edu
RI Oleske, James/C-1951-2016;
OI Oleske, James/0000-0003-2305-5605; moye, john/0000-0001-9976-8586
FU NCRR NIH HHS [M01 RR005096, RR05096]; NIAID NIH HHS [5 U01 AI41110, 1
U01 AI068616, AI068632, U01 AI041110, U01 AI068616, U01 AI068632, U01
AI068632-03]; NICHD NIH HHS [HHSN267200800001C]; NIDDK NIH HHS
[HHSN267200800001G]; PHS HHS [HHSN267200800001C, N01-3-3345]
NR 48
TC 13
Z9 13
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2010
VL 202
IS 2
BP 291
EP 301
DI 10.1086/653497
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 612VL
UT WOS:000278932900014
PM 20533872
ER
PT J
AU Polikov, VS
Hong, JS
Reichert, WM
AF Polikov, Vadim S.
Hong, Jau-Shyong
Reichert, William M.
TI Soluble factor effects on glial cell reactivity at the surface of
gel-coated microwires
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Glial scar; Gliosis; Neural precursors; Fibroblast growth factor; BFGF;
Serum; Soluble factors; Cell culture; Basal lamina
ID NEURAL STEM-CELLS; OLIGODENDROCYTE PRECURSOR CELLS; LEUKEMIA INHIBITORY
FACTOR; CILIARY NEUROTROPHIC FACTOR; FIBROBLAST GROWTH FACTOR-2;
FIBRILLARY ACIDIC PROTEIN; NERVOUS-SYSTEM; BRAIN-INJURY; SPINAL-CORD;
IN-VIVO
AB A basal lamina gel preparation was incorporated into a modified neuroinflammation cell culture model to test the system as a characterization tool for surface-modified microwires. The extent of gliosis at the surface of gel-coated microwires was quantified in response to titrating the cell culture with a number of soluble factors reported to be involved in reactive gliosis. Positive control conditions (1% FBS, 10 ng/ml bFGF, Neural Basal medium with B27 supplement) induced a layer of GFAP-expressing astrocytes to accumulate on all gel-coated microwires. Serum, inflammatory cytokines IL-l alpha and IL-1 beta and the neural progenitor cell (NPC) proliferating growth factors bFGF and PDGF all increased the number of reactive cells on the gel, in agreement with their reported roles in cell activation, migration and proliferation at the site of injury. Technically, this study shows that a fetal neuron-glia culture system is well suited for characterizing the impact of electrode coatings designed to mitigate implant-associated gliosis, and for screening the effect of multiple soluble factors that promote and/or inhibit implant-associated gliosis. Scientifically, this study points to essential roles of serum and inflammatory factors to induce NPC activation and migration to the site of injury, where growth factors like bFGF and PDGF induce proliferation of cells that will eventually form the glial scar. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Polikov, Vadim S.; Reichert, William M.] Duke Univ, Durham, NC 27708 USA.
[Hong, Jau-Shyong] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
RP Reichert, WM (reprint author), Duke Univ, 136 Hudson Hall,Box 90281, Durham, NC 27708 USA.
EM reichert@duke.edu
FU NIEHS; Hong Lab; NS [R21NS057131]
FX VSP and WMR thank the NIEHS and the Hong Lab for their generosity and
support of this study. This work was funded by NS R21NS057131 (WMR).
NR 56
TC 7
Z9 7
U1 1
U2 10
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 JUL 15
PY 2010
VL 190
IS 2
BP 180
EP 187
DI 10.1016/j.jneumeth.2010.05.002
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630EV
UT WOS:000280256700004
PM 20470825
ER
PT J
AU Park, OK
Yoo, KY
Lee, CH
Choi, JH
Hwang, IK
Park, JH
Kwon, YG
Kim, YM
Won, MH
AF Park, Ok Kyu
Yoo, Ki-Yeon
Lee, Choong Hyun
Choi, Jung Hoon
Hwang, In Koo
Park, Jun Hong
Kwon, Young-Guen
Kim, Young-Myeong
Won, Moo-Ho
TI Arylalkylamine N-acetyltransferase (AANAT) is expressed in astrocytes
and melatonin treatment maintains AANAT in the gerbil hippocampus
induced by transient cerebral ischemia
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Ischemia/reperfusion; Hippocampus; Melatonin; Arylalkylamine
N-acetyltransferase; Astrocytes
ID DELAYED NEURONAL DEATH; OXIDATIVE STRESS; FOREBRAIN ISCHEMIA; CA1
REGION; MESSENGER-RNA; RAT-BRAIN; PYRAMIDAL CELLS; FOCAL ISCHEMIA;
PINEAL-GLAND; TIME-COURSE
AB Melatonin is synthesized from serotonin by the action of arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase. In this study, we observed cellular changes of arylalkylamine N-acetyltransferase (EC 2.3.1.87: AANAT) in the hippocampal CA1 region at various time points after ischemia/reperfusion. In vehicle-treated sham group, AANAT immunoreaction was detected in pyramidal neurons of the CA1 region. AANAT immunoreactivity in the neurons was highest 2 days and disappeared from 4 days after ischemia/reperfusion. From 3 days after ischemia/reperfusion, AANAT immunoreaction was expressed in astrocytes in the strata oriens and radiatum of the CA1 region. AANAT protein and mRNA levels were significantly increased 2 days after ischemia/reperfusion, and markedly decreased from 5 days after ischemia/reperfusion. The repeated administration of melatonin (10 mg/kg, i.p.) 3 times (once a day) to gerbils before ischemia/reperfusion significantly reduced ischemia-induced hyperactivity as well as neuronal death compared to those in the vehicle-treated ischemia group. Melatonin treatment also maintained AANAT immunoreactivity and its protein levels in the CA1 region after ischemia/reperfusion. These results suggest that the reduction of AANAT in ischemic CM region is associated with delayed neuronal death following transient ischemia, and melatonin treatment shows neuroprotection with maintenance of AANAT levels in the ischemic CA1 region. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Hwang, In Koo] Seoul Natl Univ, Dept Anat & Cell Biol, Coll Vet Med, Seoul 151742, South Korea.
[Hwang, In Koo] Seoul Natl Univ, Res Inst Vet Sci, Seoul 151742, South Korea.
[Park, Ok Kyu; Yoo, Ki-Yeon; Lee, Choong Hyun; Choi, Jung Hoon; Won, Moo-Ho] Hallym Univ, Dept Anat & Neurobiol, Coll Med, Chunchon 200702, South Korea.
[Park, Ok Kyu; Yoo, Ki-Yeon; Lee, Choong Hyun; Choi, Jung Hoon; Won, Moo-Ho] Hallym Univ, Inst Neurodegenerat & Neuroregenerat, Coll Med, Chunchon 200702, South Korea.
[Park, Jun Hong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kwon, Young-Guen] Yonsei Univ, Dept Biochem, Coll Sci, Seoul 120749, South Korea.
[Kim, Young-Myeong] Kangwon Natl Univ, Vasc Syst Res Ctr, Sch Med, Chunchon 200701, South Korea.
[Kim, Young-Myeong] Kangwon Natl Univ, Dept Mol & Cellular Biochem, Sch Med, Chunchon 200701, South Korea.
RP Hwang, IK (reprint author), Seoul Natl Univ, Dept Anat & Cell Biol, Coll Vet Med, Seoul 151742, South Korea.
EM vetmed2@snu.ac.kr; mhwon@hallym.ac.kr
FU Korea Ministry of Education, Science and Technology (Medical &
Bio-material Research Center); Korean Government (MOEHRD)
[KRF-2006-E00142]
FX The authors would like to thank Mr. Suek Han, Seung Uk Lee and Ms. Hyun
Sook Kim for their technical help in this study. This work was supported
by the Regional Core Research Program funded by the Korea Ministry of
Education, Science and Technology (Medical & Bio-material Research
Center) and by the Korea Research Foundation Grant funded by the Korean
Government (MOEHRD) (KRF-2006-E00142).
NR 47
TC 8
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD JUL 15
PY 2010
VL 294
IS 1-2
BP 7
EP 17
DI 10.1016/j.jns.2010.04.013
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 621IZ
UT WOS:000279571100002
PM 20488463
ER
PT J
AU Kanda, A
Stambolian, D
Chen, W
Curcio, CA
Abecasis, GR
Swaroop, A
AF Kanda, Atsuhiro
Stambolian, Dwight
Chen, Wei
Curcio, Christine A.
Abecasis, Goncalo R.
Swaroop, Anand
TI Age-related macular degeneration-associated variants at chromosome 10q26
do not significantly alter ARMS2 and HTRA1 transcript levels in the
human retina
SO MOLECULAR VISION
LA English
DT Article
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; GENE-EXPRESSION;
SUSCEPTIBILITY; RISK; POLYMORPHISM; DISEASE; CFH; MACULOPATHY;
MECHANISMS
AB Purpose: Multiple studies demonstrate a strong association between three variants at chromosome 10q26 - rs10490924, del443ins54, and rs11200638 - near the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HTRA1) genes with susceptibility to age-related macular degeneration (AMD). In different reports, the del443ins54 and rs11200638 variants are suggested to affect ARMS2 mRNA stability and/or HTRA1 mRNA expression, respectively. The goal of this study is to examine whether these AMD-associated variants alter expression levels of ARMS2 and HTRA1 in human retina samples.
Methods: Genomic DNA and total RNA were obtained from 35 human retinas (three young controls, average age=32 years; twenty aged controls, average age=72 years; and twelve AMD retinas, average age=77 years) using standard procedures. As ARMS2 exhibits higher expression in the human placenta, we also included eighteen placenta samples in our analysis. Four polymorphisms - rs2736911, rs10490924, del443ins54, and rs11200638 - were genotyped by PCR followed by sequencing. Expression of ARMS2, HTRA1 and three endogenous control genes (rRNA [rRNA], hypoxanthine phosphoribosyltransferase 1 [HPRT1], and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) was measured by real-time quantitative RT-PCR using Taqman gene expression or SYBR Green assays.
Results: ARMS2 and HTRA1 mRNA levels did not show a significant difference in expression among the control (young and elderly) and AMD retinas. No association of del443ins54 and rs11200638 variants was detected with mRNA expression levels of ARMS2 or HTRA1 in the retina. Human placenta samples showed high variability in expression levels.
Conclusions: We did not find association between AMD susceptibility variants at 10q26 and steady-state expression levels of either ARMS2 or HTRA1 in the human retina.
C1 [Kanda, Atsuhiro; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol & Human Genet, Philadelphia, PA 19104 USA.
[Chen, Wei; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Curcio, Christine A.] Univ Alabama, Dept Ophthalmol, Birmingham, AL 35294 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 6-338,MSC0610,6 Ctr Dr, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Abecasis, Goncalo/B-7840-2010;
OI Abecasis, Goncalo/0000-0003-1509-1825; Swaroop,
Anand/0000-0002-1975-1141
FU National Eye Institute; Foundation Fighting Blindness; Research to
Prevent Blindness; International Retinal Research Foundation
FX We thank Matthew Brooks, Tiziana Cogliati and members of the Swaroop
laboratory for advice and comments. This work was supported by
intramural funds and grants from the National Eye Institute, The
Foundation Fighting Blindness, and Research to Prevent Blindness. Also,
this work was supported from International Retinal Research Foundation
(C.C.).
NR 35
TC 32
Z9 32
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUL 15
PY 2010
VL 16
IS 145-50
BP 1317
EP 1323
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 643GN
UT WOS:000281283700001
PM 20664794
ER
PT J
AU Fang, F
Xu, Q
Park, Y
Huang, XM
Hollenbeck, A
Blair, A
Schatzkin, A
Kamel, F
Chen, HL
AF Fang, Fang
Xu, Qun
Park, Yikyung
Huang, Xuemei
Hollenbeck, Albert
Blair, Aaron
Schatzkin, Arthur
Kamel, Freya
Chen, Honglei
TI Depression and the Subsequent Risk of Parkinson's Disease in the
NIH-AARP Diet and Health Study
SO MOVEMENT DISORDERS
LA English
DT Article
DE depression; Parkinson's disease; odds ratio
ID COHORT; SYSTEM; ANTIDEPRESSANTS; EPIDEMIOLOGY; POPULATION; PATHOLOGY;
DOPAMINE; REGISTER; ILLNESS; BRAIN
AB We conducted a case-control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH-AARP Diet and Health Study follow-up survey. Physician-diagnosed depression and PD were self-reported with information on the year of diagnosis in the following categories: before 1985, 1985-1994, 1995-1999, and 2000-present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995-1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985-1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% Cl = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD. (C) 2010 Movement Disorder Society
C1 [Fang, Fang; Xu, Qun; Kamel, Freya; Chen, Honglei] NIEHS, Epidemiol Branch, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA.
[Fang, Fang] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Park, Yikyung; Schatzkin, Arthur] Natl Canc Inst, Nutr Epidemiol Branch, Rockville, MD USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol Radiol Neurosurg Pharmacol Kinesiol &, Hershey, PA 17033 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, US Dept HHS, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615; Chen,
Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU NIH, National Institute of Environmental Health Sciences
[Z01-ES-101986]; National Institute of Cancer [Z01-CP010196-02]; NIH
[NS060722]
FX The study was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (Z01-ES-101986) and
the National Institute of Cancer (Z01-CP010196-02). Dr. Huang is
supported by NIH extramural grant (NS060722). The authors thank the
participants of the NIH-AARP Diet and Health Study for their
contributions. We also thank Dr. Xuguang Guo for programming advice.
NR 28
TC 28
Z9 31
U1 3
U2 7
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 JUL 15
PY 2010
VL 25
IS 9
BP 1157
EP 1162
DI 10.1002/mds.23092
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 636YN
UT WOS:000280781500007
PM 20310050
ER
PT J
AU Schmid, MC
Mrowka, SW
Turchi, J
Saunders, RC
Wilke, M
Peters, AJ
Ye, FQ
Leopold, DA
AF Schmid, Michael C.
Mrowka, Sylwia W.
Turchi, Janita
Saunders, Richard C.
Wilke, Melanie
Peters, Andrew J.
Ye, Frank Q.
Leopold, David A.
TI Blindsight depends on the lateral geniculate nucleus
SO NATURE
LA English
DT Article
ID VISUAL RESPONSE PROPERTIES; SUPERIOR COLLICULUS; AREA MT; STRIATE
CORTEX; MACAQUE MONKEY; GANGLION-CELLS; AFFERENT BASIS; PROJECTION;
NEURONS; ACTIVATION
AB Injury to the primary visual cortex (V1) leads to the loss of visual experience. Nonetheless, careful testing shows that certain visually guided behaviours can persist even in the absence of visual awareness(1-4). The neural circuits supporting this phenomenon, which is often termed blindsight, remain uncertain(4). Here we demonstrate that the thalamic lateral geniculate nucleus (LGN) has a causal role in V1-independent processing of visual information. By comparing functional magnetic resonance imaging (fMRI) and behavioural measures with and without temporary LGN inactivation, we assessed the contribution of the LGN to visual functions of macaque monkeys (Macaca mulatta) with chronic V1 lesions. Before LGN inactivation, high-contrast stimuli presented to the lesion-affected visual field (scotoma) produced significant V1-independent fMRI activation in the extrastriate cortical areas V2, V3, V4, V5/middle temporal (MT), fundus of the superior temporal sulcus (FST) and lateral intraparietal area (LIP) and the animals correctly located the stimuli in a detection task. However, following reversible inactivation of the LGN in the V1-lesioned hemisphere, fMRI responses and behavioural detection were abolished. These results demonstrate that direct LGN projections to the extrastriate cortex have a critical functional contribution to blindsight. They suggest a viable pathway to mediate fast detection during normal vision.
C1 [Schmid, Michael C.; Mrowka, Sylwia W.; Turchi, Janita; Saunders, Richard C.; Wilke, Melanie; Peters, Andrew J.; Leopold, David A.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
[Ye, Frank Q.; Leopold, David A.] NEI, Neurophysiol Imaging Facil, NIMH, NINDS, Bethesda, MD 20892 USA.
RP Schmid, MC (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr, Bethesda, MD 20892 USA.
EM schmidmicha@gmail.com
RI Schmid, Michael/G-1867-2010;
OI Schmid, Michael/0000-0003-1424-130X; Peters, Andrew/0000-0001-9351-1456;
Leopold, David/0000-0002-1345-6360
FU NIMH; NINDS; NEI
FX We thank A. Maier and D. McMahon for comments on the manuscript; S.
Smirnakis, R. Berman, R. Wurtz, B. Richmond, S. Guderian and M.
Fukushima for discussions; C. Zhu and H. Merkle for magnetic resonance
coil construction; K. Smith, N. Phipps, J. Yu, G. Dold, D. Ide and T.
Talbot for technical assistance; D. Sheinberg for developing visual
stimulation software; and members of the Brian Wandell laboratory for
developing and sharing mrVista software. This work was supported by the
Intramural Research Programme of the NIMH, the NINDS, and the NEI.
NR 30
TC 127
Z9 129
U1 8
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 373
EP 377
DI 10.1038/nature09179
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100050
PM 20574422
ER
PT J
AU Song, H
Hu, JX
Chen, W
Elliott, G
Andre, P
Gao, B
Yang, YZ
AF Song, Hai
Hu, Jianxin
Chen, Wen
Elliott, Gene
Andre, Philipp
Gao, Bo
Yang, Yingzi
TI Planar cell polarity breaks bilateral symmetry by controlling ciliary
positioning
SO NATURE
LA English
DT Article
ID LEFT-RIGHT ASYMMETRY; NODAL EXPRESSION; GENE-EXPRESSION; SITUS-INVERSUS;
LEFTWARD FLOW; PATHWAYS; MOUSE; ESTABLISHMENT; POLARIZATION; REGULATOR
AB Defining the three body axes is a central event of vertebrate morphogenesis. Establishment of left-right (L-R) asymmetry in development follows the determination of dorsal-ventral and anterior-posterior (A-P) body axes 1,2, although the molecular mechanism underlying precise L-R symmetry breaking in reference to the other two axes is still poorly understood. Here, by removing both Vangl1 and Vangl2, the two mouse homologues of a Drosophila core planar cell polarity (PCP) gene Van Gogh (Vang), we reveal a previously unrecognized function of PCP in the initial breaking of lateral symmetry. The leftward nodal flow across the posterior notochord (PNC) has been identified as the earliest event in the de novo formation of L-R asymmetry(3,4). We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry. In the absence of Vangl1 and Vangl2, cilia are positioned randomly around the centre of the PNC cells and nodal flow is turbulent, which results in disrupted L-R asymmetry. PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells. Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.
C1 [Song, Hai; Hu, Jianxin; Chen, Wen; Andre, Philipp; Gao, Bo; Yang, Yingzi] 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, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
FU National Human Genome Research Institute
FX We thank members of the Yang laboratory for stimulating discussion; M.
Kuehn, A. Kumar and J. Regard for critical reading of the manuscript; J.
Fekecs and D. Leja for preparing the graphics; D. Wu for teaching us to
dissect the mouse cochlea; and M. Kelley for the anti-Vangl2 antibodies.
This study is supported by the intramural research programme of National
Human Genome Research Institute.
NR 32
TC 141
Z9 141
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 378
EP U130
DI 10.1038/nature09129
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100051
PM 20562861
ER
PT J
AU Stonnington, CM
Chu, C
Kloppel, S
Jack, CR
Ashburner, J
Frackowiak, RSJ
AF Stonnington, Cynthia M.
Chu, Carlton
Kloeppel, Stefan
Jack, Clifford R., Jr.
Ashburner, John
Frackowiak, Richard S. J.
CA Alzheimer Dis Neuroimaging
TI Predicting clinical scores from magnetic resonance scans in Alzheimer's
disease
SO NEUROIMAGE
LA English
DT Article
DE Alzheimer's disease; Multivariate; Machine learning; Relevance vector
regression; MMSE; DRS; AVLT; ADAS-Cog
ID MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY;
PATTERN-CLASSIFICATION; APOLIPOPROTEIN-E; BRAIN ATROPHY; RATING-SCALE;
MRI; DIAGNOSIS; AD; SEGMENTATION
AB Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3 months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set: 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE. ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Stonnington, Cynthia M.] Mayo Clin, Div Adult Psychiat, Dept Psychiat & Psychol, Scottsdale, AZ 85259 USA.
[Stonnington, Cynthia M.; Chu, Carlton; Kloeppel, Stefan; Ashburner, John] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London, England.
[Chu, Carlton] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Kloeppel, Stefan] Univ Clin Freiburg, Dept Psychiat & Psychotherapy, Sect Gerontopsychiat & Neuropsychol & Freiburg Br, Freiburg, Germany.
[Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Frackowiak, Richard S. J.] CHU Vaudois, Serv Neurol, CH-1011 Lausanne, Switzerland.
[Frackowiak, Richard S. J.] IRCCS Santa Lucia, Lab Neuroimaging, Rome, Italy.
RP Stonnington, CM (reprint author), Mayo Clin, Div Adult Psychiat, Dept Psychiat & Psychol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM stonnington.cynthia@mayo.edu
RI Jack, Clifford/F-2508-2010; Frackowiak, Richard/I-1809-2013; Ashburner,
John/I-3757-2013; Frackowiak, Richard/H-4383-2011
OI Jack, Clifford/0000-0001-7916-622X; Ashburner, John/0000-0001-7605-2518;
Frackowiak, Richard/0000-0002-3151-822X
FU Wellcome Trust [075696 2/04/2]; Mayo Clinic; National Institute on Aging
[P50 AG16574, U01 AG06786, AG11378]; Robert H. and Clarice Smith and
Abigail Van Buren Alzheimer's Disease Research Program; Mayo Foundation;
Alzheimer's disease Neuroimaging Initiative (ADNI); National Institutes
of Health [U01 AG024904]; National Institute on Aging, the National
Institute of Biomedical Imaging and Bioengineering
FX This work was supported by the Wellcome Trust (grant 075696 2/04/2 to
R.S.J.F.), Mayo Clinic (grant to C.M.S.), the National Institute on
Aging (grants P50 AG16574, U01 AG06786, and AG11378 to Mayo Clinic
Rochester, MN), the Robert H. and Clarice Smith and Abigail Van Buren
Alzheimer's Disease Research Program, and the Alexander Family
Alzheimer's Disease Research Professorship of the Mayo Foundation (to
Mayo Clinic Rochester, MN), Alzheimer's disease Neuroimaging Initiative
(ADNI; Principal Investigator: Michael Weiner; National Institutes of
Health grant U01 AG024904); ADNI is funded by the National Institute on
Aging, the National Institute of Biomedical Imaging and Bioengineering.
The authors thank Kewei Chen, PhD, Justin Venditti, and Eric Reiman, MD
for help with the ADNI data set and thoughtful suggestions.
NR 48
TC 87
Z9 88
U1 2
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2010
VL 51
IS 4
BP 1405
EP 1413
DI 10.1016/j.neuroimage.2010.03.051
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 601EV
UT WOS:000278042000013
PM 20347044
ER
PT J
AU Robinson, OJ
Frank, MJ
Sahakian, BJ
Cools, R
AF Robinson, Oliver J.
Frank, Michael J.
Sahakian, Barbara J.
Cools, Roshan
TI Dissociable responses to punishment in distinct striatal regions during
reversal learning
SO NEUROIMAGE
LA English
DT Article
ID NUCLEUS-ACCUMBENS; ORBITOFRONTAL CORTEX; REWARD PREDICTION; DORSOLATERAL
STRIATUM; PARKINSONS PATIENTS; DOPAMINE NEURONS; DECISION-MAKING; BASAL
GANGLIA; HUMAN BRAIN; BEHAVIOR
AB Adaptive behavior depends on the ability to flexibly alter our choices in response to changes in reward and punishment contingencies. One brain region frequently implicated in such behavior is the striatum. However, this region is functionally diverse and there are a number of apparent inconsistencies across previous studies. For instance, how can significant BOLD responses in the ventral striatum during punishment-based reversal learning be reconciled with the frequently demonstrated role of the ventral striatum in reward processing? Here we attempt to address this question by separately examining BOLD responses during reversal learning driven by reward and during reversal learning driven by punishment. We demonstrate simultaneous valence-specific and valence-nonspecific signals in the striatum, with the posterior dorsal striatum responding only to unexpected reward, and the anterior ventral striatum responding to both unexpected punishment as well as unexpected reward. These data help to reconcile conflicting findings from previous studies by showing that distinct regions of the striatum exhibit dissociable responses to punishment during reversal learning. Published by Elsevier Inc.
C1 [Robinson, Oliver J.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England.
[Robinson, Oliver J.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England.
[Robinson, Oliver J.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Frank, Michael J.] Brown Univ, Dept Cognit & Linguist Sci, Dept Psychol, Brown Inst Brain Sci,Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Cools, Roshan] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, Dept Psychiat,Med Ctr, NL-6525 ED Nijmegen, Netherlands.
RP Robinson, OJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, POB 189,Level E4,Hills Rd, Cambridge CB2 2QQ, England.
EM oliver.j.robinson@googlemail.com
RI Robinson, Oliver/B-3646-2011; Cools, Roshan/D-1905-2010
OI Robinson, Oliver/0000-0002-3100-1132;
FU Medical Research Council; Wellcome Trust [076274/Z/04/Z]; Gates
Cambridge Trust
FX This work was completed within the University of Cambridge Behavioural
and Clinical Neuroscience Institute, funded by a joint award from the
Medical Research Council and the Wellcome Trust. Additional funding for
this study came from Wellcome Trust Programme Grant 076274/Z/04/Z
awarded to T.W.R., B. J. Everitt, A. C. Roberts, and B. J. Sahakian.
M.J.C. is supported by the Gates Cambridge Trust. We thank the nurses
and administrative staff at the Wellcome Trust Clinical Research
Facility (Addenbrooke's Hospital, Cambridge, UK) and all participants.
NR 55
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Z9 37
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2010
VL 51
IS 4
BP 1459
EP 1467
DI 10.1016/j.neuroimage.2010.03.036
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 601EV
UT WOS:000278042000019
PM 20303408
ER
PT J
AU Frost, NA
Shroff, H
Kong, HH
Betzig, E
Blanpied, TA
AF Frost, Nicholas A.
Shroff, Hari
Kong, Huihui
Betzig, Eric
Blanpied, Thomas A.
TI Single-Molecule Discrimination of Discrete Perisynaptic and Distributed
Sites of Actin Filament Assembly within Dendritic Spines
SO NEURON
LA English
DT Article
ID LONG-TERM POTENTIATION; CLATHRIN-MEDIATED ENDOCYTOSIS; AMPA-RECEPTORS;
LOCALIZATION MICROSCOPY; HIPPOCAMPAL-NEURONS; ARP2/3 COMPLEX;
NERVOUS-SYSTEM; F-ACTIN; PLASTICITY; DYNAMICS
AB Within dendritic spines, actin is presumed to anchor receptors in the postsynaptic density and play numerous roles regulating synaptic transmission. However, the submicron dimensions of spines have hindered examination of actin dynamics within them and prevented live-cell discrimination of perisynaptic actin filaments. Using photoactivated localization microscopy, we measured movement of individual actin molecules within living spines. Velocity of single actin molecules along filaments, an index of filament polymerization rate, was highly heterogeneous within individual spines. Most strikingly, molecular velocity was elevated in discrete, well-separated foci occurring not principally at the spine tip, but in subdomains throughout the spine, including the neck. Whereas actin velocity on filaments at the synapse was substantially elevated, at the endocytic zone there was no enhanced polymerization activity. We conclude that actin subserves spatially diverse, independently regulated processes throughout spines. Perisynaptic actin forms a uniquely dynamic structure well suited for direct, active regulation of the synapse.
C1 [Frost, Nicholas A.; Kong, Huihui; Blanpied, Thomas A.] Univ Maryland, Sch Med, Dept Physiol & Program Neurosci, Baltimore, MD 21201 USA.
[Shroff, Hari; Betzig, Eric] Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
[Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, Bethesda, MD 20892 USA.
RP Blanpied, TA (reprint author), Univ Maryland, Sch Med, Dept Physiol & Program Neurosci, Baltimore, MD 21201 USA.
EM tblanpied@som.umaryland.edu
RI Kong, Huihui/F-9024-2012; Shroff, Hari/E-7247-2016;
OI Shroff, Hari/0000-0003-3613-8215; Blanpied, Thomas/0000-0003-4957-557X
FU Summer Training in Aging Research Topics Mental Health (Start-MH)
fellowship; NIGMS [T32GM008181]; NRSA [F30MH086185]; NIMH [R01MH080046];
Dana Foundation; Katherine D. and Theodore J. Carski Foundation
FX We thank the following for supplying plasmids: S. McKinney
(mEos2-actin), B. Imhof (GFP-actin), G. Patterson (PA-GFP), M. Rizzo
(cerulean), J. Lippincott-Schwartz (tdEos-paxillin), D. Bredt
(PSD-95-GFP), R.Y. Tsien (tdTomato, mCherry), G. Feng (GKAP), and M.
Davidson (Dronpa). We thank also J. Kerr and H. Lu for helpful
discussions, and M. Ehlers, J. Bear, and S. Thompson for comments on the
manuscript. Support was provided by a Summer Training in Aging Research
Topics Mental Health (Start-MH) fellowship; Training Grant NIGMS
T32GM008181, and NRSA F30MH086185 (NAF) and NIMH R01MH080046; the Dana
Foundation; and the Katherine D. and Theodore J. Carski Foundation
(TAB). E.B. is coowner of Hestzig LLC, which has exclusively licensed
PALM technology to Carl Zeiss MicroImaging, GmbH.
NR 67
TC 122
Z9 123
U1 1
U2 27
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 15
PY 2010
VL 67
IS 1
BP 86
EP 99
DI 10.1016/j.neuron.2010.05.026
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 629SW
UT WOS:000280221000011
PM 20624594
ER
PT J
AU Bromberg-Martin, ES
Matsumoto, M
Hikosaka, O
AF Bromberg-Martin, Ethan S.
Matsumoto, Masayuki
Hikosaka, Okihide
TI Distinct Tonic and Phasic Anticipatory Activity in Lateral Habenula and
Dopamine Neurons
SO NEURON
LA English
DT Article
ID MIDBRAIN DOPAMINE; NUCLEUS-ACCUMBENS; REWARD PREDICTION; AVERSIVE
STIMULI; MONKEY MIDBRAIN; RESPONSES; BEHAVIOR; SIGNAL; MOTIVATION;
SALIENCE
AB Dopamine has a crucial role in anticipation of motivational events. To investigate the underlying mechanisms of this process, we analyzed the activity of dopamine neurons and one of their major sources of input, neurons in the lateral habenula, while animals anticipated upcoming behavioral tasks. We found that lateral habenula and dopamine neurons anticipated tasks in two distinct manners. First, neurons encoded the timing distribution of upcoming tasks through gradual changes in their tonic activity. This tonic signal encoded rewarding tasks in preference to punishing tasks and was correlated with classic phasic coding of motivational value. Second, neurons transmitted a phasic signal marking the time when a task began. This phasic signal encoded rewarding and punishing tasks in similar manners, as though reflecting motivational salience. Our data suggest that the habenula-dopamine pathway motivates anticipation through a combination of tonic reward-related and phasic salience-related signals.
C1 [Bromberg-Martin, Ethan S.; Matsumoto, Masayuki; Hikosaka, Okihide] NIH, Sensorimotor Res Lab, Natl Eye Inst, Bethesda, MD 20892 USA.
[Matsumoto, Masayuki] Kyoto Univ, Primate Res Inst, Aichi 4848506, Japan.
RP Bromberg-Martin, ES (reprint author), NIH, Sensorimotor Res Lab, Natl Eye Inst, Bldg 10, Bethesda, MD 20892 USA.
EM bromberge@mail.nih.gov
FU National Eye Institute
FX We thank H. Nakahara, S. Kaveri, T. Yang, L. Paninski, S. Hong, M.
Yasuda, S. Yamamoto, Y. Tachibana, and H. Kim for valuable discussions.
This work was supported by the intramural research program at the
National Eye Institute.
NR 52
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Z9 61
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 15
PY 2010
VL 67
IS 1
BP 144
EP 155
DI 10.1016/j.neuron.2010.06.016
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 629SW
UT WOS:000280221000015
PM 20624598
ER
PT J
AU Stone, JH
Merkel, PA
Spiera, R
Seo, P
Langford, CA
Hoffman, GS
Kallenberg, CGM
Clair, EWS
Turkiewicz, A
Tchao, NK
Webber, L
Ding, L
Sejismundo, LP
Mieras, K
Weitzenkamp, D
Ikle, D
Seyfert-Margolis, V
Mueller, M
Brunetta, P
Allen, NB
Fervenza, FC
Geetha, D
Keogh, KA
Kissin, EY
Monach, PA
Peikert, T
Stegeman, C
Ytterberg, SR
Specks, U
AF Stone, John H.
Merkel, Peter A.
Spiera, Robert
Seo, Philip
Langford, Carol A.
Hoffman, Gary S.
Kallenberg, Cees G. M.
Clair, E. William St.
Turkiewicz, Anthony
Tchao, Nadia K.
Webber, Lisa
Ding, Linna
Sejismundo, Lourdes P.
Mieras, Kathleen
Weitzenkamp, David
Ikle, David
Seyfert-Margolis, Vicki
Mueller, Mark
Brunetta, Paul
Allen, Nancy B.
Fervenza, Fernando C.
Geetha, Duvuru
Keogh, Karina A.
Kissin, Eugene Y.
Monach, Paul A.
Peikert, Tobias
Stegeman, Coen
Ytterberg, Steven R.
Specks, Ulrich
CA RAVE-ITN Res Grp
TI Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTIBODY-ASSOCIATED VASCULITIS; GRANULOMATOSIS ETANERCEPT TRIAL;
WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; SYSTEMIC VASCULITIDES;
CELL-ACTIVATION; B-CELLS; THERAPY; INDUCTION; REMISSION
AB Background: Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen.
Methods: We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months.
Results: Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events.
Conclusions: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)
N Engl J Med 2010;363:221-32.
C1 [Specks, Ulrich] Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Merkel, Peter A.; Kissin, Eugene Y.; Monach, Paul A.] Boston Univ, Med Ctr, Boston, MA USA.
[Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA.
[Seo, Philip; Sejismundo, Lourdes P.; Geetha, Duvuru] Johns Hopkins Univ, Baltimore, MD USA.
[Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Groningen, Netherlands.
[Clair, E. William St.; Allen, Nancy B.] Duke Univ, Durham, NC USA.
[Turkiewicz, Anthony] Univ Alabama, Birmingham, AL USA.
[Tchao, Nadia K.; Seyfert-Margolis, Vicki; Mueller, Mark] Immune Tolerance Network, Bethesda, MD USA.
[Webber, Lisa; Ding, Linna] NIAID, Bethesda, MD 20892 USA.
[Seyfert-Margolis, Vicki] US FDA, Rockville, MD 20857 USA.
[Brunetta, Paul] Genentech Inc, San Francisco, CA 94080 USA.
[Weitzenkamp, David; Ikle, David] Rho, Raleigh, NC USA.
RP Specks, U (reprint author), Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA.
EM specks.ulrich@mayo.edu
OI Carey, John/0000-0001-7292-2328
FU National Institute of Allergy and Infectious Diseases [N01-AI-15416,
ITN021AI]; Mayo Clinic and Foundation; National Center for Research
Resources (NCRR) [RR024150-01, RR025005, K24 AR049185, K23 AR052820];
Boston University; National Institutes of Health [RR 025771, M01
RR00533, K24 AR02224]; Arthritis Foundation
FX Supported by a grant from the National Institute of Allergy and
Infectious Diseases to the Immune Tolerance Network (N01-AI-15416;
protocol no. ITN021AI). Genentech and Biogen provided the study
medications and partial funding. At the Mayo Clinic and Foundation, the
trial was supported by a Clinical and Translational Science Award from
the National Center for Research Resources (NCRR) (RR024150-01); at
Johns Hopkins University, by grants from the NCRR (RR025005) and career
development awards (K24 AR049185, to Dr. Stone, and K23 AR052820, to Dr.
Seo); and at Boston University, by a Clinical and Translational Science
Award (RR 025771), grants from the National Institutes of Health (M01
RR00533) and a career development award (K24 AR02224, to Dr. Merkel),
and an Arthritis Foundation Investigator Award (to Dr. Monach).
Enzyme-linked immunosorbent assay kits for antineutrophil cytoplasmic
antibody were provided by Euroimmun (Lubeck, Germany).
NR 35
TC 748
Z9 784
U1 2
U2 32
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 JUL 15
PY 2010
VL 363
IS 3
BP 221
EP 232
DI 10.1056/NEJMoa0909905
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 625AR
UT WOS:000279864200005
PM 20647199
ER
PT J
AU Chew, EY
Ambrosius, WT
Davis, MD
Danis, RP
Gangaputra, S
Greven, CM
Hubbard, L
Esser, BA
Lovato, JF
Perdue, LH
Goff, DC
Cushman, WC
Ginsberg, HN
Elam, MB
Genuth, S
Gerstein, HC
Schubart, U
Fine, LJ
AF Chew, Emily Y.
Ambrosius, Walter T.
Davis, Matthew D.
Danis, Ronald P.
Gangaputra, Sapna
Greven, Craig M.
Hubbard, Larry
Esser, Barbara A.
Lovato, James F.
Perdue, Letitia H.
Goff, David C., Jr.
Cushman, William C.
Ginsberg, Henry N.
Elam, Marshall B.
Genuth, Saul
Gerstein, Hertzel C.
Schubart, Ulrich
Fine, Lawrence J.
CA ACCORD Study Grp
ACCORD Eye Study Grp
TI Effects of Medical Therapies on Retinopathy Progression in Type 2
Diabetes.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BLOOD-PRESSURE CONTROL; MICROVASCULAR COMPLICATIONS; GLUCOSE CONTROL;
CONTROLLED-TRIAL; MACULAR EDEMA; HARD EXUDATE; MELLITUS; RISK
AB Background: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.
Methods: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy.
Results: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29).
Conclusions: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)
N Engl J Med 2010;363:233-44.
C1 [Chew, Emily Y.] NEI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Ambrosius, Walter T.; Greven, Craig M.; Lovato, James F.; Perdue, Letitia H.; Goff, David C., Jr.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Davis, Matthew D.; Danis, Ronald P.; Gangaputra, Sapna; Hubbard, Larry; Esser, Barbara A.] Univ Wisconsin, Madison, WI 53706 USA.
[Cushman, William C.; Elam, Marshall B.] Vet Affairs Med Ctr, Memphis, TN USA.
[Ginsberg, Henry N.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Genuth, Saul] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada.
[Schubart, Ulrich] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Fine, Lawrence J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, NIH, Clin Res Ctr, Bldg 10,Rm 3-2531,10 Ctr Dr,Mail Stop Ctr 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
RI Friedewald, William/C-8034-2011
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of Health; National
Institute of Diabetes and Digestive and Kidney Diseases; National Eye
Institute; National Institute on Aging; Centers for Disease Control and
Prevention; General Clinical Research Centers; Merck and money;
Novartis; Takeda; Sanofi-Aventis; Bristol-Myers Squibb; King
Pharmaceuticals; Daiichi-Sankyo; Gilead; Theravance; Pharmacopeia;
Sciele; GlaxoSmithKline; Merck; Abbott-AstraZeneca; Roche; Isis-Genzyme;
Pfizer; Regeneron-Sanofi-Aventis
FX Supported by contracts (N01-HC-95178, N01-HC-95179, N01-HC-95180,
N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035,
and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute
and the National Institutes of Health, with additional support from the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Eye Institute, the National Institute on Aging, and the Centers
for Disease Control and Prevention. General Clinical Research Centers
provided support at many sites. The following companies donated study
medications, equipment, or supplies: Abbott Laboratories, Amylin
Pharmaceutical, AstraZeneca Pharmaceuticals, Bayer HealthCare, Closer
Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals,
Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare,
SanofiAventis U.S., and Takeda Pharmaceuticals.; Dr. Goff reports
receiving grant support or pending grant support from Merck and money
for serving as a data and safety monitoring board member for a trial of
a diabetes medication from Takeda; Dr. Cushman, consulting fees from
Novartis, Takeda, Sanofi-Aventis, Bristol-Myers Squibb, King
Pharmaceuticals, Daiichi-Sankyo, Gilead, Theravance, Pharmacopeia, and
Sciele and grant support or pending grant support from Novartis,
GlaxoSmithKline, and Merck; Dr. Ginsberg, advisory fees from Merck,
Merck-Schering Plough, and Bristol-Myers SquibbAstraZeneca; consulting
fees from Merck, Abbott-AstraZeneca, Bristol-Myers Squibb, Roche,
Isis-Genzyme, GlaxoSmithKline, Novartis, Pfizer, and
Regeneron-Sanofi-Aventis; grant support or pending grant support from
Merck, Isis-Genzyme, Roche, and AstraZeneca; payment for development of
education presentations from Pfizer; and payment for travel and
accommodation expenses from all these companies; Dr. Elam, payment for
development of education presentations from Pfizer, Abbott
Pharmaceuticals, and Merck-Schering Plough; and Dr. Gerstein, consulting
fees from Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo Nordisk,
AstraZeneca, Bristol-Myers Squibb, Roche, Medtronic, Merck, Bayer,
Bioavail, and Jansen Ortho; grant support or pending grant support from
Sanofi-Aventis, GlaxoSmithKline, Novo Nordisk, Merck, Pronova, and
Roche; honoraria from Sanofi-Aventis, GlaxoSmithKline, Solvay,
Boehringer Ingelheim, Servier, Bayer, Eli Lilly, Novo Nordisk, and
Takeda; and payment for travel and accommodation expenses from all these
companies; Dr. Schubart reports participating in trials sponsored by
Sanofi-Aventis, Merck, and Johnson & Johnson. No other potential
conflict of interest relevant to this article was reported.
NR 27
TC 381
Z9 399
U1 0
U2 38
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 JUL 15
PY 2010
VL 363
IS 3
BP 233
EP 244
DI 10.1056/NEJMoa1001288
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 625AR
UT WOS:000279864200006
ER
PT J
AU Severe, P
Juste, MAJ
Ambroise, A
Eliacin, L
Marchand, C
Apollon, S
Edwards, A
Bang, H
Nicotera, J
Godfrey, C
Gulick, RM
Johnson, WD
Pape, JW
Fitzgerald, DW
AF Severe, Patrice
Juste, Marc Antoine Jean
Ambroise, Alex
Eliacin, Ludger
Marchand, Claudel
Apollon, Sandra
Edwards, Alison
Bang, Heejung
Nicotera, Janet
Godfrey, Catherine
Gulick, Roy M.
Johnson, Warren D., Jr.
Pape, Jean William
Fitzgerald, Daniel W.
TI Early versus Standard Antiretroviral Therapy for HIV-Infected Adults in
Haiti.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; RANDOMIZED-TRIAL; CLINICAL-TRIALS;
COTE-DIVOIRE; SOUTH-AFRICA; TUBERCULOSIS; AIDS; COHORT; PROPHYLAXIS;
PROGRESSION
AB Background: For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.
Methods: We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support.
Results: Between 2005 and 2008, a total of 816 participants -- 408 per group -- were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P=0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P=0.01).
Conclusions: Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)
N Engl J Med 2010;363:257-65.
C1 [Fitzgerald, Daniel W.] Weill Cornell Med Coll, Ctr Global Hlth, Div Infect Dis, Dept Med, New York, NY 10065 USA.
[Severe, Patrice; Juste, Marc Antoine Jean; Ambroise, Alex; Eliacin, Ludger; Marchand, Claudel; Apollon, Sandra; Pape, Jean William] GHESKIO, Port Au Prince, Haiti.
[Edwards, Alison; Bang, Heejung] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Nicotera, Janet] Vanderbilt Univ, Dept Pediat, Nashville, TN USA.
[Godfrey, Catherine] NIAID, Bethesda, MD 20892 USA.
RP Fitzgerald, DW (reprint author), Weill Cornell Med Coll, Ctr Global Hlth, Div Infect Dis, Dept Med, Rm A-421,1300 York Ave, New York, NY 10065 USA.
EM dfitzgerald@gheskio.org
FU National Institute of Allergy and Infectious Diseases [AI58257, AI69421,
AI51966]; Fogarty International Center [TW006896, TW006901, TW 00018];
Fondation Merieux
FX Supported in part by grants from the National Institute of Allergy and
Infectious Diseases (AI58257, AI69421, and AI51966) and from the Fogarty
International Center (TW006896, TW006901, and TW 00018). Support for
antiretroviral medications was provided by the Global Fund to Fight
AIDS, Tuberculosis, and Malaria, GlaxoSmithKline, and Abbott. Laboratory
training and infrastructure were supported by a grant from Fondation
Merieux.
NR 34
TC 209
Z9 217
U1 0
U2 10
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 JUL 15
PY 2010
VL 363
IS 3
BP 257
EP 265
DI 10.1056/NEJMoa0910370
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 625AR
UT WOS:000279864200008
PM 20647201
ER
PT J
AU Fishler, T
Li, YY
Wang, RH
Kim, HS
Sengupta, K
Vassilopoulos, A
Lahusen, T
Xu, X
Lee, MH
Liu, Q
Elledge, SJ
Ried, T
Deng, CX
AF Fishler, T.
Li, Y-Y
Wang, R-H
Kim, H-S
Sengupta, K.
Vassilopoulos, A.
Lahusen, T.
Xu, X.
Lee, M-H
Liu, Q.
Elledge, S-J
Ried, T.
Deng, C-X
TI Genetic instability and mammary tumor formation in mice carrying
mammary-specific disruption of Chk1 and p53
SO ONCOGENE
LA English
DT Article
DE Chk1; mitotic catastrophe; genome integrity; mammary cancer; SB-218078
ID CELL-CYCLE CHECKPOINT; CONDITIONAL KNOCKOUT MICE; C-NEU ONCOGENE;
PHASE-I TRIAL; DNA-DAMAGE; SPINDLE CHECKPOINT; BREAST-CANCER; BRCA1;
KINASE; INHIBITOR
AB Checkpoint kinase 1 (Chk1) is a key element in the DNA-damage response pathway that is required for maintaining genomic stability. To study the potential role of Chk1 in mammary tumorigenesis, we disrupted it using a Cre/loxP system. We showed that although Chk1 heterozygosity caused abnormal development of the mammary gland, it was not sufficient to induce tumorigenesis. Simultaneous deletion of one copy of p53 failed to rescue the developmental defects; however, it synergistically induced mammary tumor formation in Chk(;)(1+/-) MMTV-Cre animals with a median time to tumor latency of about 10 months. Chk1 deficiency caused a preponderance of abnormalities, including prolongation, multipolarity, misalignment, mitotic catastrophe and loss of spindle checkpoint, that are accompanied by reduced expression of several cell cycle regulators, including Mad2. On the other hand, we also showed that Chk1 deficiency inhibited mammary tumor formation in mice carrying a homozygous deletion of p53, uncovering a complex relationship between Chk1 and p53. Furthermore, inhibition of Chk1 with a specific inhibitor, SB-218078, or acute deletion of Chk1 using small hairpin RNA killed mammary tumor cells effectively. These data show that Chk1 is critical for maintaining genome integrity and serves as a double-edged sword for cancer: although its inhibition kills cancer cells, it also triggers tumorigenesis when favorable mutations are accumulated for cell growth. Oncogene (2010) 29, 4007-4017; doi:10.1038/onc.2010.163; published online 17 May 2010
C1 [Deng, C-X] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Sengupta, K.; Ried, T.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Q.; Elledge, S-J] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10 Rm 9N105, Bethesda, MD 20892 USA.
EM chuxiad@bdg10.niddk.nih.gov
RI deng, chuxia/N-6713-2016
FU National Institute of Diabetes, Digestive and Kidney Diseases, National
Institutes of Health, USA
FX We gratefully acknowledge members of Deng laboratory for a critical
reading of the article. This work was supported by the Intramural
Research Program of the National Institute of Diabetes, Digestive and
Kidney Diseases, National Institutes of Health, USA.
NR 48
TC 26
Z9 27
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL 15
PY 2010
VL 29
IS 28
BP 4007
EP 4017
DI 10.1038/onc.2010.163
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 625JW
UT WOS:000279892400002
PM 20473325
ER
PT J
AU Takizawa, M
Kim, JS
Tessarollo, L
McNeil, N
Waldschmidt, TJ
Casellas, R
Ried, T
Janz, S
AF Takizawa, M.
Kim, J. S.
Tessarollo, L.
McNeil, N.
Waldschmidt, T. J.
Casellas, R.
Ried, T.
Janz, S.
TI Genetic reporter system for oncogenic Igh-Myc translocations in mice
SO ONCOGENE
LA English
DT Article
DE mouse plasmacytoma T(12;15) translocation; human Burkitt lymphoma
t(8;14)(q24;q32) translocation; green fluorescence protein
ID CLASS SWITCH RECOMBINATION; C-MYC; CHROMOSOMAL TRANSLOCATIONS; B-CELL;
BALB/C PLASMACYTOMAS; DNA-REPAIR; IN-VIVO; T(12/15); AID; HYPERMUTATION
AB The Myc-deregulating chromosomal T(12; 15)(Igh-Myc) translocation, the hallmark mutation of inflammation-and interleukin 6-dependent mouse plasmacytoma (PCT), is the premier model of cancer-associated chromosomal translocations because it is the only translocation in mice that occurs spontaneously (B lymphocyte lineage) and with predictably high incidence (similar to 85% of PCT), and has a direct counterpart in humans: Burkitt lymphoma t(8;14)(q24;q32) translocation. Here, we report on the development of a genetic system for the detection of T(12;15)(Igh-Myc) translocations in plasma cells of a mouse strain in which an enhanced green fluorescent protein (GFP)-encoding reporter gene has been targeted to Myc. Four of the PCTs that developed in the newly generated translocation reporter mice, designated iGFP(5/Myc), expressed GFP consequent to naturally occurring T(12;15) translocation. GFP expression did not interfere with tumor development or the deregulation of Myc on derivative 12 of translocation, der (12), because the reporter gene was allocated to the reciprocal product of translocation, der (15). Although the described reporter gene approach requires refinement before T(12;15) translocations can be quantitatively detected in vivo, including in B lymphocyte lineage cells that have not yet completed malignant transformation, our findings provide proof of principle that reporter gene tagging of oncogenes in gene-targeted mice can be used to elucidate unresolved questions on the occurrence, distribution and trafficking of cells that have acquired cancer-causing chromosomal translocations of great relevance for humans. Oncogene (2010) 29, 4113-4120; doi:10.1038/onc.2010.150; published online 10 May 2010
C1 [Waldschmidt, T. J.; Janz, S.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52246 USA.
[Takizawa, M.; Kim, J. S.] NCI, Genet Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Takizawa, M.; Casellas, R.] Natl Inst Arthrit & Musculoskeletal Dis, Bethesda, MD USA.
[Tessarollo, L.] NCI, Mouse Canc Genet Program, CCR, Bethesda, MD 20892 USA.
[McNeil, N.; Ried, T.] NCI, Genet Branch, CCR, NIH, Bethesda, MD 20892 USA.
RP Janz, S (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, 500 Newton Rd,1046C ML, Iowa City, IA 52246 USA.
EM siegfried-janz@uiowa.edu
FU NIH; National Cancer Institute [P50CA097274]
FX We thank our colleagues from NCI and NIAID, NIH for their contributions
to this project: Tina Willington, Vaishali Jarral and Wendy DuBois for
genotyping and assistance with the mouse experiments; Eileen Southon for
gene targeting; Dr Alexander L Kovalchuk for advice on PCR analysis and
providing primers; Drs Sung Sup Park and Santiago Silva for
contributions to early stages of this project; and Drs Michael Potter
and Beverly Mock for stimulating discussion and laboratory support. For
assistance with transfer, cryopreservation, maintenance and rederivation
of mice under SPF conditions, we thank: Ling Hu, CCOM, Iowa City, Iowa;
the staff of the Jackson Laboratory, Bar Harbor, Maine; and the Office
of Animal Resources, CCOM, particularly Dr Kem Singletary and James
Hynes. We also thank Lorraine Tygrett, CCOM for assistance with flow
cytometry. This work was supported, in part, by the Intramural Research
Program of the NIH (LT, RC, TR) and Award Number P50CA097274 from the
National Cancer Institute (SJ).
NR 31
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUL 15
PY 2010
VL 29
IS 28
BP 4113
EP 4120
DI 10.1038/onc.2010.150
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 625JW
UT WOS:000279892400011
PM 20453890
ER
PT J
AU Maris, JM
Morton, CL
Gorlick, R
Kolb, EA
Lock, R
Carol, H
Keir, ST
Reynolds, CP
Kang, MH
Wu, JR
Smith, MA
Houghton, PJ
AF Maris, John M.
Morton, Christopher L.
Gorlick, Richard
Kolb, E. Anders
Lock, Richard
Carol, Hernan
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Wu, Jianrong
Smith, Malcolm A.
Houghton, Peter J.
TI Initial Testing of the Aurora Kinase A Inhibitor MLN8237 by the
Pediatric Preclinical Testing Program (PPTP)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE preclinical testing; developmental therapeutics; MLN8237
ID XENOGRAFT MODELS; CANCER MODELS; DRUG TARGETS; IN-VIVO; N-MYC;
CHECKPOINT; PROTEIN; AGENTS; CELLS; GENE
AB Background. MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis. Procedures. MLN8237 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM to 10 mu M and was tested against the PPTP in vivo panels at a dose of 20 mg/kg administered orally twice daily x 5 days. Treatment duration was 6 weeks for solid tumor xenografts and 3 weeks for ALL xenografts. Results. MLN8237 had a median IC(50) of 61 nM against the PPTP in vitro panel. The ALL cell lines were more sensitive and the rhabdomyosarcoma cell lines less sensitive than the remaining PPTP cell lines. In vivo, MLN8237 induced significant differences in event-free survival (EFS) distributions compared to controls in 32/40 (80%) solid tumor models and all (6/6) ALL models. Maintained complete responses (CRs) were observed in 3 of 7 neuroblastoma xenografts, and all 6 evaluable ALL xenografts achieved CR (n = 4) or maintained CR (n = 2) status. Maintained CRs were observed among single xenografts in other panels, including the Wilms tumor, rhabdoid tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and medulloblastoma. Conclusions. The in vivo activity observed against the neuroblastoma panel far exceeds that observed for standard agents evaluated against the panel by the PPTP. High levels of in vivo activity were also observed against the ALL xenograft panel. These data support expedited clinical development of MLN8237 in childhood cancer. Pediatr Blood Cancer 2010;55:26-34. (C) 2010 Wiley-Liss, Inc.
C1 [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Morton, Christopher L.; Wu, Jianrong; Houghton, Peter J.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Maris, JM (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM maris@chop.edu
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA 108786]
FX This work was supported by NO1-CM-42216, CA21765, and CA 108786 from the
National Cancer Institute and used MLN8237 supplied by Millennium
Pharmaceuticals, Inc. In addition to the authors represents work
contributed by the following: Sherry Ansher, Catherine A. Billups,
Joshua Courtright, Edward Favours, Henry S. Friedman, Debbie
Payne-Turner, Charles Stopford, Chandra Tucker, Amy E. Watkins, Joe
Zeidner, Ellen Zhang, and Jian Zhang. Children's Cancer Institute
Australia for Medical Research is affiliated with the University of New
South Wales and Sydney Children's Hospital.
NR 34
TC 106
Z9 114
U1 1
U2 12
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL 15
PY 2010
VL 55
IS 1
BP 26
EP 34
DI 10.1002/pbc.22430
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 601BJ
UT WOS:000278032700011
PM 20108338
ER
PT J
AU Carey, MA
Bradbury, JA
Rebolloso, YD
Graves, JP
Zeldin, DC
Germolec, DR
AF Carey, Michelle A.
Bradbury, J. Alyce
Rebolloso, Yvette D.
Graves, Joan P.
Zeldin, Darryl C.
Germolec, Dori R.
TI Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral
Infection in Mice
SO PLOS ONE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; G-CSF; ALLERGIC INFLAMMATION;
IMMUNE-RESPONSE; DEFICIENT MICE; VIRUS; HYPOTHERMIA; CYCLOOXYGENASES;
PROSTAGLANDINS; GRANULOCYTE
AB Background: We previously demonstrated that cyclooxygenase (COX)-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice.
Methodology/Principal Findings: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560), a COX-2 inhibitor (celecoxib) or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU) and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL) fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control.
Conclusions/Significance: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.
C1 [Carey, Michelle A.; Bradbury, J. Alyce; Rebolloso, Yvette D.; Graves, Joan P.; Zeldin, Darryl C.; Germolec, Dori R.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Carey, MA (reprint author), NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health
FX Supported by the Intramural Research Program of the National Institute
of Environmental Health Sciences, 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 40
TC 23
Z9 24
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 15
PY 2010
VL 5
IS 7
AR e11610
DI 10.1371/journal.pone.0011610
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625VR
UT WOS:000279924500012
PM 20657653
ER
PT J
AU Screpanti, E
Santaguida, S
Nguyen, T
Silvestri, R
Gussio, R
Musacchio, A
Hamel, E
De Wulf, P
AF Screpanti, Emanuela
Santaguida, Stefano
Nguyen, Tam
Silvestri, Romano
Gussio, Rick
Musacchio, Andrea
Hamel, Ernest
De Wulf, Peter
TI A Screen for Kinetochore-Microtubule Interaction Inhibitors Identifies
Novel Antitubulin Compounds
SO PLOS ONE
LA English
DT Article
ID NDC80 COMPLEX; CELL-LINES; TUBULIN; COLCHICINE; AGENTS; VINBLASTINE;
BINDING; CANCER; DRUGS
AB Background: Protein assemblies named kinetochores bind sister chromatids to the mitotic spindle and orchestrate sister chromatid segregation. Interference with kinetochore activity triggers a spindle checkpoint mediated arrest in mitosis, which frequently ends in cell death. We set out to identify small compounds that inhibit kinetochore-microtubule binding for use in kinetochore-spindle interaction studies and to develop them into novel anticancer drugs.
Methodology/Principal Findings: A fluorescence microscopy-based in vitro assay was developed to screen compound libraries for molecules that prevented the binding of a recombinant human Ndc80 kinetochore complex to taxol-stabilized microtubules. An active compound was identified that acted at the microtubule level. More specifically, by localizing to the colchicine-binding site in ab-tubulin the hit compound prevented the Ndc80 complex from binding to the microtubule surface. Next, structure-activity analyses distinguished active regions in the compound and led to the identification of highly potent analogs that killed cancer cells with an efficacy equaling that of established spindle drugs.
Conclusions/Significance: The compound identified in our screen and its subsequently identified analogs represent new antitubulin chemotypes that can be synthetically developed into a novel class of antimitotic spindle drugs. In addition, they are stereochemically unique as their R- and S-isomers mimic binding of colchicine and podophyllotoxin, respectively, two antitubulin drugs that interact differently with the tubulin interface. Model-driven manipulation of our compounds promises to advance insight into how antitubulin drugs act upon tubulin. These advances in turn may lead to tailor-made colchicine site agents which would be valuable new assets to fight a variety of tumors, including those that have become resistant to the (antispindle) drugs used today.
C1 [Screpanti, Emanuela; Santaguida, Stefano; Musacchio, Andrea; De Wulf, Peter] European Inst Oncol, Dept Expt Oncol, Milan, Italy.
[Nguyen, Tam; Gussio, Rick] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA.
[Silvestri, Romano] Univ Roma La Sapienza, Dept Med Chem & Technol, Rome, Italy.
[Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA.
RP Screpanti, E (reprint author), European Inst Oncol, Dept Expt Oncol, IFOM IEO Campus, Milan, Italy.
EM peter.dewulf@ifom-ieo-campus.it
RI santaguida, stefano/G-2716-2010;
OI Santaguida, Stefano/0000-0002-1501-6190; De Wulf,
Peter/0000-0001-9772-5881; Silvestri, Romano/0000-0003-2489-0178;
Musacchio, Andrea/0000-0003-2362-8784
FU Istituto Pasteur - Fondazione Cenci Bolognetti; Progetti di Ricerca di
Universita-Anno; Universita di Roma; Associazione Italiana per la
Ricerca sul Cancro; Association of International Cancer Research;
Fondazione Italiana per la Ricerca sul Cancro
FX This research was supported by grants from the Istituto Pasteur -
Fondazione Cenci Bolognetti
(http://www.istitutopasteur.it/site/index.php), and Progetti di Ricerca
di Universita-Anno 2008, Universita di Roma "La Sapienza''
(http://www.uniroma1.it/) to RS, grant 4535 from the Associazione
Italiana per la Ricerca sul Cancro (http://www.AIRC.it) to AM, and grant
08-0465 from the Association of International Cancer Research
(http://www.AICR.org.uk) to PDW. ES and SS acknowledge a post-doctoral
and doctoral fellowship, respectively, from the Fondazione Italiana per
la Ricerca sul Cancro (http://www.fondazionefirc.it). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 23
TC 11
Z9 12
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 15
PY 2010
VL 5
IS 7
AR e11603
DI 10.1371/journal.pone.0011603
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625VR
UT WOS:000279924500007
PM 20657644
ER
PT J
AU Gao, XH
Yu, LD
Castro, L
Moore, AB
Hermon, T
Bortner, C
Sifre, M
Dixon, D
AF Gao, Xiaohua
Yu, Linda
Castro, Lysandra
Moore, Alicia B.
Hermon, Tonia
Bortner, Carl
Sifre, Maria
Dixon, Darlene
TI An endocrine-disrupting chemical, fenvalerate, induces cell cycle
progression and collagen type I expression in human uterine leiomyoma
and myometrial cells
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Leiomyoma; Myometrium; Fenvalerate; Cell growth; ECM; Collagen type I
ID HORMONE REPLACEMENT THERAPY; PYRETHROID INSECTICIDES;
EXTRACELLULAR-MATRIX; TUMOR-GROWTH; IGF-I; ESTROGEN; FIBROIDS;
PROLIFERATION; ETIOLOGY; KINASE
AB Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 mu M) had a stimulatory effect on the growth of both cell lines at 24 h compared with controls by MIS (p < 0.01) and BrdU (p < 0.01) assays in hormonally responsive uterine leiomyoma (UtLM) cells and normal uterine smooth muscle cells (UtSMC). Flow cytometry results showed that Fen enhanced the escape of cells from the G(0)-G(1) checkpoint and promoted progression of both cell types into the S phase. An Annexin V assay showed that Fen had an anti-apoptotic effect on both cell types. By Real-time PCR, we found that collagen I mRNA expression increased (p < 0.05) in Fen-treated cells compared to controls, although it was greater in UtLM tumor cells. Accordingly. Fen increased (p < 0.05) collagen I protein levels in both cell lysate and supernatant when compared to controls. To further test the mechanism of Fen's effects, transactivation and competitive binding assays were done. The results showed Fen did not significantly stimulate luciferase activity at concentrations of 0.1 mu M, 1.0 mu M or 10.0 mu M in either of the cell types. Competitive binding assays revealed that the affinity of Fen binding to estrogen receptors (ERs) was non-detectable compared to E-2. Our data show that Fen can stimulate the growth of both UtLM cells and UtSMC, which involves a combination of enhanced cell cycle progression and inhibition of apoptosis. Also this compound can increase collagen I expression, at both mRNA and protein levels. Interestingly, the ER is less likely involved in either the hyperplasia or extracellular matrix (ECM) overproduction induced by Fen. Our results indicate that Fen exposure could be considered a novel risk factor for uterine fibroids through molecular mechanisms that do not directly involve the ERs. Published by Elsevier Ireland Ltd.
C1 [Gao, Xiaohua; Yu, Linda; Castro, Lysandra; Moore, Alicia B.; Hermon, Tonia; Dixon, Darlene] NIEHS, Comparat Pathobiol Grp, Cellular & Mol Pathol Branch, NTP,NIH,DHHS, Res Triangle Pk, NC 27709 USA.
[Bortner, Carl; Sifre, Maria] NIEHS, Flow Cytometly Ctr, Lab Signal Transduct, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Dixon, D (reprint author), NIEHS, Comparat Pathobiol Grp, Cellular & Mol Pathol Branch, NTP,NIH,DHHS, POB 12233,MDC2-09-C254,111 TW Alexander Dr,Bldg 1, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
RI Gao, Xiaohua/D-2699-2012
FU NIH, National Institute of Environmental Health Sciences
FX The authors kindly thank Dr. Gordon Flake and Ms. Retha Newbold for
their critical review of this manuscript. We also thank Dr. Grace E.
Kissling in the Biostatistics Branch, NIEHS for statistical data
analysis, and Kathleen A. Wallace in the Environmental Carcinogenesis
Division of the USEPA (Research Triangle Park, NC) for her expert
technical support on fluorescence polarization. This research was
supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences.
NR 46
TC 16
Z9 16
U1 2
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
EI 1879-3169
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUL 15
PY 2010
VL 196
IS 3
BP 133
EP 141
DI 10.1016/j.toxlet.2010.03.004
PG 9
WC Toxicology
SC Toxicology
GA 617VY
UT WOS:000279311200001
PM 20230880
ER
PT J
AU Hall, KD
AF Hall, Kevin D.
TI Mathematical modelling of energy expenditure during tissue deposition
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Mathematical modelling; Energy expenditure; Tissue deposition; Weight
gain
ID MAINTENANCE REQUIREMENTS; PROTEIN DEPOSITION; GROWING PIGS; BODY-WEIGHT;
FAT; COST; EFFICIENCY; OBESITY; GROWTH
AB Predicting the magnitude and rate of weight gain for a given increase of energy intake requires a model of whole-body energy expenditure that includes the energy cost of tissue deposition. Here, I introduce a mathematical framework for modelling energy expenditure that elucidates conceptual problems with the classical Kielanowski method for estimating the efficiencies of body fat and protein deposition. An alternative approach uses the theoretical biochemical efficiencies for protein and fat synthesis in combination with models of energy expenditure that include body fat and protein turnover costs. I illustrate this alternative approach using a simple mathematical model applied to previously published data from growing rats and human infants and compare the simple model results with the classical Kielanowski model. While both models fit the data reasonably well (R(2) > 0.87 in rats and R(2) > 0.67 in infants), the Kielanowski method resulted in parameter estimates that varied widely across experiments, had poor precision, and occasionally produced efficiency estimates greater than 1. In contrast, the new method provided precise parameter values and revealed consistencies across different experiments. The proposed mathematical framework has implications for interpreting studies of animal nutrition as well as providing a roadmap for future modelling efforts.
C1 NIDDKD, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDKD, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
RI Hall, Kevin/F-2383-2010
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases (NIH/NIDDK)
FX The present study was supported by the Intramural Research Program of
the National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases (NIH/NIDDK).
NR 20
TC 23
Z9 23
U1 1
U2 11
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUL 14
PY 2010
VL 104
IS 1
BP 4
EP 7
DI 10.1017/S0007114510000206
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 623NM
UT WOS:000279748400002
PM 20132585
ER
PT J
AU Vikram, B
AF Vikram, Bhadrasain
TI Conventional and High-Dose Radiation in Treating Early Prostate Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 NCI, Clin Radiat Oncol Branch, Rockville, MD 20852 USA.
RP Vikram, B (reprint author), NCI, Clin Radiat Oncol Branch, Rockville, MD 20852 USA.
EM vikramb@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2010
VL 304
IS 2
BP 155
EP 155
DI 10.1001/jama.2010.927
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624IN
UT WOS:000279811000012
PM 20628123
ER
PT J
AU Korn, EL
Freidlin, B
Mooney, M
AF Korn, Edward L.
Freidlin, Boris
Mooney, Margaret
TI Bias and Trials Stopped Early for Benefit
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID BREAST-CANCER; TRASTUZUMAB
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Mooney, Margaret] NCI, CTEP, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 5
TC 6
Z9 6
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2010
VL 304
IS 2
BP 157
EP 158
DI 10.1001/jama.2010.932
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624IN
UT WOS:000279811000017
PM 20628125
ER
PT J
AU Migueles, SA
Connors, M
AF Migueles, Stephen A.
Connors, Mark
TI Long-term Nonprogressive Disease Among Untreated HIV-Infected
Individuals Clinical Implications of Understanding Immune Control of HIV
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; VIRAL REPLICATION
CAPACITY; LOW-LEVEL VIREMIA; HLA-C ALLELES; ANTIRETROVIRAL THERAPY;
ELITE SUPPRESSORS; TYPE-1 INFECTION; HIV-1-INFECTED PATIENTS; LYMPHOCYTE
ACTIVATION
AB As of 2008, more than 33 million adults and children have been estimated to be living with human immunodeficiency virus (HIV). Among them are rare patients (<0.5%) who have remained clinically well without antiretroviral therapy after almost 20 years of infection. They maintain stable CD4 cell counts and suppressed HIV replication to levels comparable with those measured in patients receiving combination antiretroviral therapy. No known epidemiologic or behavioral factors are predictive of untreated, nonprogressive HIV infection; however, host genetics and immune response factors, most specifically HLA antigen class I-restricted HIV-specific CD8 T cells, appear to be primarily responsible for this remarkable phenotype in a majority of these individuals. These patients offer hope that durable control of HIV infection is possible and can provide important insight to inform the development of the next generation of HIV/AIDS vaccines and immune-based therapies. This article reviews clinical features of these unique patients and discusses them in the context of nonprogressors enrolled in other cohorts. Potential mechanisms underlying nonprogressive HIV infection and scientific discoveries, facilitated by the participation of these patients in clinical trials, of relevance to the design of an efficacious HIV/AIDS vaccine are also highlighted. JAMA. 2010; 304(2): 194-201 www.jama.com
C1 [Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-07, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 67
TC 66
Z9 66
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2010
VL 304
IS 2
BP 194
EP 201
DI 10.1001/jama.2010.925
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624IN
UT WOS:000279811000026
PM 20628133
ER
PT J
AU Drazen, JM
de Leeuw, PW
Laine, C
Mulrow, C
DeAngelis, CD
Frizelle, FA
Godlee, F
Haug, C
Hebert, PC
James, A
Kotzin, S
Marusic, A
Reyes, H
Rosenberg, J
Sahni, P
Van der Weyden, MB
Zhaori, G
AF Drazen, Jeffrey M.
de Leeuw, Peter W.
Laine, Christine
Mulrow, Cynthia
DeAngelis, Catherine D.
Frizelle, Frank A.
Godlee, Fiona
Haug, Charlotte
Hebert, Paul C.
James, Astrid
Kotzin, Sheldon
Marusic, Ana
Reyes, Humberto
Rosenberg, Jacob
Sahni, Peush
Van der Weyden, Martin B.
Zhaori, Getu
TI Toward More Uniform Conflict Disclosures The Updated ICMJE Conflict of
Interest Reporting Form
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kotzin, Sheldon] Natl Lib Med, Bethesda, MD 20894 USA.
RP Mulrow, C (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA.
EM cmulrow@mail.acponline.org
RI Marusic, Ana/E-7683-2013
OI Marusic, Ana/0000-0001-6272-0917
NR 0
TC 13
Z9 13
U1 0
U2 3
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 JUL 14
PY 2010
VL 304
IS 2
BP 212
EP 213
DI 10.1001/jama.2010.918
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624IN
UT WOS:000279811000032
PM 20595375
ER
PT J
AU Jain, L
Sissung, TM
Danesi, R
Kohn, EC
Dahut, WL
Kummar, S
Venzon, D
Liewehr, D
English, BC
Baum, CE
Yarchoan, R
Giaccone, G
Venitz, J
Price, DK
Figg, WD
AF Jain, Lokesh
Sissung, Tristan M.
Danesi, Romano
Kohn, Elise C.
Dahut, William L.
Kummar, Shivaani
Venzon, David
Liewehr, David
English, Bevin C.
Baum, Caitlin E.
Yarchoan, Robert
Giaccone, Giuseppe
Venitz, Juergen
Price, Douglas K.
Figg, William D.
TI Hypertension and hand-foot skin reactions related to VEGFR2 genotype and
improved clinical outcome following bevacizumab and sorafenib
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ANTITUMOR-ACTIVITY; TARGETED THERAPY; DOMAIN
RECEPTOR; PROSTATE-CANCER; ANGIOGENESIS; POLYMORPHISMS; TOXICITIES;
TRIAL
AB Background: Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes.
Methods: Toxicities (>= grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes.
Results: Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136).
Conclusions: This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.
C1 [Jain, Lokesh; Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jain, Lokesh; Venitz, Juergen] Virginia Commonwealth Univ, Dept Pharmaceut, Sch Pharm, Richmond, VA 23298 USA.
[Sissung, Tristan M.; Kohn, Elise C.; Dahut, William L.; Kummar, Shivaani; Giaccone, Giuseppe; Price, Douglas K.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Danesi, Romano] Univ Pisa, Dept Internal Med, I-56126 Pisa, Italy.
[Venzon, David; Liewehr, David] Natl Canc Inst, Biostat & Data Management Sect, Rockville, MD 20852 USA.
[English, Bevin C.; Baum, Caitlin E.; Figg, William D.] NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016; Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU National Cancer Institute, National Institutes of Health, Bethesda, MD
FX This study was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health, Bethesda,
MD. We thank our data managers Cynthia Graves, Sonja Crandon, Qinghua Ge
(Roger), Shveta Tiwari, and Kathleen Wyvill, and most of all, our
patients who participated in these trials. 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 organization imply endorsement by the
U.S. Government.
NR 23
TC 51
Z9 51
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-9966
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD JUL 14
PY 2010
VL 29
AR 95
DI 10.1186/1756-9966-29-95
PG 8
WC Oncology
SC Oncology
GA 656NO
UT WOS:000282343700001
PM 20630084
ER
PT J
AU Thakker-Varia, S
Jean, YY
Parikh, P
Sizer, CF
Ayer, JJ
Parikh, A
Hyde, TM
Buyske, S
Alder, J
AF Thakker-Varia, Smita
Jean, Ying Y.
Parikh, Payal
Sizer, Caroline F.
Ayer, Jennifer Jernstedt
Parikh, Ankit
Hyde, Thomas M.
Buyske, Steven
Alder, Janet
TI The Neuropeptide VGF Is Reduced in Human Bipolar Postmortem Brain and
Contributes to Some of the Behavioral and Molecular Effects of Lithium
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; ELEMENT-BINDING PROTEIN; NORMAL HUMAN
CORTEX; NEUROTROPHIC FACTOR; MAJOR DEPRESSION; ANIMAL-MODELS;
CYTOARCHITECTONIC DEFINITION; ELECTROCONVULSIVE SEIZURES; NEUROPATHOLOGY
CONSORTIUM; HIPPOCAMPAL-FORMATION
AB Recent studies demonstrate that the neuropeptide VGF (nonacronymic) is regulated in the hippocampus by antidepressant therapies and animal models of depression and that acute VGF treatment has antidepressant-like activity in animal paradigms. However, the role of VGF in human psychiatric disorders is unknown. We now demonstrate using in situ hybridization that VGF is downregulated in bipolar disorder in the CA region of the hippocampus and Brodmann's area 9 of the prefrontal cortex. The mechanism of VGF in relation to LiCl was explored. Both LiCl intraperitoneally and VGF intracerebroventricularly reduced latency to drink in novelty-induced hypophagia, and LiCl was not effective in VGF(+/-) mice, suggesting that VGF may contribute to the effects of LiCl in this behavioral procedure that responds to chronic antidepressant treatment. VGF by intrahippocampal injection also had novel activity in an amphetamine-induced hyperlocomotion assay, thus mimicking the actions of LiCl injected intraperitoneally in a system that phenocopies manic-like behavior. Moreover, VGF(+/-) mice exhibited increased locomotion after amphetamine treatment and did not respond to LiCl, suggesting that VGF is required for the effects of LiCl in curbing the response to amphetamine. Finally, VGF delivered intracerebroventricularly in vivo activated the same signaling pathways as LiCl and is necessary for the induction of mitogen-activated protein kinase and Akt by LiCl, thus lending insight into the molecular mechanisms underlying the actions of VGF. The dysregulation of VGF in bipolar disorder as well as the behavioral effects of the neuropeptide similar to LiCl suggests that VGF may underlie the pathophysiology of bipolar disorder.
C1 [Alder, Janet] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Robert Wood Johnson Sch Publ Hlth 357A, Piscataway, NJ 08854 USA.
[Hyde, Thomas M.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat, Piscataway, NJ 08854 USA.
RP Alder, J (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Robert Wood Johnson Sch Publ Hlth 357A, 675 Hoes Lane W, Piscataway, NJ 08854 USA.
EM alderja@umdnj.edu
OI Alder, Janet/0000-0002-5694-4946; Buyske, Steven/0000-0001-8539-5416
FU National Alliance for Research on Schizophrenia and Depression;
Foundation of the University of Medicine and Dentistry of New Jersey
FX This work was funded by a grant from the National Alliance for Research
on Schizophrenia and Depression and the Foundation of the University of
Medicine and Dentistry of New Jersey. We thank Sujata Kumar for help
with silver grain counting of the frontal cortex, Dr. Chung-Lin Chang
(Senior Veterinarian) for necropsy of LiCl-treated mice, and Michael
Ansonoff for assistance with repeated-measures ANOVA. VGF+/-
mice were generated by Regeneron and provided by Dr. Steve Salton.
Postmortem tissue was provided from the brain collection of the Stanley
Medical Research Institute, courtesy of Drs. Michael B. Knable, E.
Fuller Torrey, Maree J. Webster, Serge Weis, and Robert H. Yolken.
NR 93
TC 22
Z9 24
U1 1
U2 3
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 JUL 14
PY 2010
VL 30
IS 28
BP 9368
EP 9380
DI 10.1523/JNEUROSCI.5987-09.2010
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 625MJ
UT WOS:000279899100005
PM 20631166
ER
PT J
AU Lynall, ME
Bassett, DS
Kerwin, R
McKenna, PJ
Kitzbichler, M
Muller, U
Bullmore, ET
AF Lynall, Mary-Ellen
Bassett, Danielle S.
Kerwin, Robert
McKenna, Peter J.
Kitzbichler, Manfred
Muller, Ulrich
Bullmore, Edward T.
TI Functional Connectivity and Brain Networks in Schizophrenia
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GRAPH-THEORETICAL ANALYSIS; SMALL-WORLD NETWORKS; RESTING-STATE FMRI;
CEREBRAL-CORTEX; COGNITIVE NEUROSCIENCE; DISCONNECTION SYNDROME;
PSYCHIATRIC-DISORDERS; LIKELIHOOD ESTIMATION; ALZHEIMERS-DISEASE;
DEFAULT NETWORK
AB Schizophrenia has often been conceived as a disorder of connectivity between components of large-scale brain networks. We tested this hypothesis by measuring aspects of both functional connectivity and functional network topology derived from resting-state fMRI time series acquired at 72 cerebral regions over 17 min from 15 healthy volunteers (14 male, 1 female) and 12 people diagnosed with schizophrenia (10 male, 2 female). We investigated between-group differences in strength and diversity of functional connectivity in the 0.06-0.125 Hz frequency interval, and some topological properties of undirected graphs constructed from thresholded interregional correlation matrices. In people with schizophrenia, strength of functional connectivity was significantly decreased, whereas diversity of functional connections was increased. Topologically, functional brain networks had reduced clustering and small-worldness, reduced probability of high-degree hubs, and increased robustness in the schizophrenic group. Reduced degree and clustering were locally significant in medial parietal, premotor and cingulate, and right orbitofrontal cortical nodes of functional networks in schizophrenia. Functional connectivity and topological metrics were correlated with each other and with behavioral performance on a verbal fluency task. We conclude that people with schizophrenia tend to have a less strongly integrated, more diverse profile of brain functional connectivity, associated with a less hub-dominated configuration of complex brain functional networks. Alongside these behaviorally disadvantageous differences, however, brain networks in the schizophrenic group also showed a greater robustness to random attack, pointing to a possible benefit of the schizophrenia connectome, if less extremely expressed.
C1 [Lynall, Mary-Ellen; Bassett, Danielle S.; Kitzbichler, Manfred; Muller, Ulrich; Bullmore, Edward T.] Univ Cambridge, Dept Psychiat, Cambridge CB2 0SZ, England.
[Lynall, Mary-Ellen; Bassett, Danielle S.; Kitzbichler, Manfred; Muller, Ulrich; Bullmore, Edward T.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 0SZ, England.
[Bassett, Danielle S.] NIMH, Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Bassett, Danielle S.] Univ Cambridge, Dept Phys, Biol Soft Syst Sector, Cambridge CB3 0HE, England.
[Kerwin, Robert] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
[McKenna, Peter J.] Ctr Invest Red Salut Mental, Barcelona 08840, Spain.
[Bullmore, Edward T.] GlaxoSmithKline, Clin Unit Cambridge, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
RP Bullmore, ET (reprint author), Univ Cambridge, Dept Psychiat, Herchel Smith Bldg Brain & Mind Sci,Cambridge Bio, Cambridge CB2 0SZ, England.
EM etb23@cam.ac.uk
RI Bullmore, Edward/C-1706-2012;
OI Bullmore, Edward/0000-0002-8955-8283; Lynall,
Mary-Ellen/0000-0002-1939-7525; McKenna, Peter/0000-0001-5474-1144
FU National Institute of Mental Health; National Institute of Biomedical
Imaging and Bioengineering; Bristol Myers Squibb; National Institutes of
Health; Instituto de Salud Carlos III, Centro de Investigacion en Red de
Salut Mental, CIBERSAM
FX This research was supported by a Human Brain Project grant from the
National Institute of Mental Health and the National Institute of
Biomedical Imaging and Bioengineering. Data acquisition was supported by
a grant from Bristol Myers Squibb. D.S.B. was supported by the National
Institutes of Health-Cambridge Graduate Partnership Program. P.J.M. was
supported by the Instituto de Salud Carlos III, Centro de Investigacion
en Red de Salut Mental, CIBERSAM. We thank Dr. Rebecca Jones for her
contribution to patient recruitment, and Glyn Johnson for supervising
fMRI acquisition at the BUPA Lea Hospital (Cambridge, UK).
NR 74
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U2 105
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 JUL 14
PY 2010
VL 30
IS 28
BP 9477
EP 9487
DI 10.1523/JNEUROSCI.0333-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 625MJ
UT WOS:000279899100015
PM 20631176
ER
PT J
AU Orjuela-Sanchez, P
Karunaweera, ND
da Silva-Nunes, M
da Silva, NS
Scopel, KKG
Goncalves, RM
Amaratunga, C
Sa, JM
Socheat, D
Fairhust, RM
Gunawardena, S
Thavakodirasah, T
Galapaththy, GLN
Abeysinghe, R
Kawamoto, F
Wirth, DF
Ferreira, MU
AF Orjuela-Sanchez, Pamela
Karunaweera, Nadira D.
da Silva-Nunes, Monica
da Silva, Natal S.
Scopel, Kezia K. G.
Goncalves, Raquel M.
Amaratunga, Chanaki
Sa, Juliana M.
Socheat, Duong
Fairhust, Rick M.
Gunawardena, Sharmini
Thavakodirasah, Thuraisamy
Galapaththy, Gawrie L. N.
Abeysinghe, Rabindra
Kawamoto, Fumihiko
Wirth, Dyann F.
Ferreira, Marcelo U.
TI Single-nucleotide polymorphism, linkage disequilibrium and geographic
structure in the malaria parasite Plasmodium vivax: prospects for
genome-wide association studies
SO BMC GENETICS
LA English
DT Article
ID BRAZILIAN AMAZON REGION; CHLOROQUINE RESISTANCE; POPULATION-STRUCTURE;
TRANSMISSION DYNAMICS; MOLECULAR MARKERS; NATURAL-SELECTION; ALLELIC
DIVERSITY; GENETIC-STRUCTURE; HAPLOTYPE BLOCKS; RURAL AMAZONIA
AB Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized.
Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance.
Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.
C1 [Orjuela-Sanchez, Pamela; da Silva-Nunes, Monica; da Silva, Natal S.; Scopel, Kezia K. G.; Goncalves, Raquel M.; Ferreira, Marcelo U.] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508900 Sao Paulo, Brazil.
[Karunaweera, Nadira D.; Gunawardena, Sharmini] Univ Colombo, Fac Med, Dept Parasitol, Colombo 8, Sri Lanka.
[da Silva-Nunes, Monica] Univ Fed Acre, Ctr Hlth Sci, BR-69915900 Rio Branco, Acre, Brazil.
[Scopel, Kezia K. G.] Univ Fed Juiz de Fora, Inst Biol Sci, BR-36036330 Juiz De Fora, MG, Brazil.
[Amaratunga, Chanaki; Sa, Juliana M.; Fairhust, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Socheat, Duong] Natl Malaria Ctr, Phnom Penh 1, Cambodia.
[Thavakodirasah, Thuraisamy; Galapaththy, Gawrie L. N.; Abeysinghe, Rabindra] Minist Hlth, Colombo 10, Sri Lanka.
[Kawamoto, Fumihiko] Oita Univ, Inst Sci Res, Dept Social & Environm Med, Oita 8795593, Japan.
[Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Ferreira, MU (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508900 Sao Paulo, Brazil.
EM muferrei@usp.br
RI Ferreira, Marcelo/G-8289-2011; da Silva-Nunes, Monica/A-1885-2008; da
Silva, Natal Santos/E-9579-2015
OI Ferreira, Marcelo/0000-0002-5293-9090; da Silva, Natal
Santos/0000-0002-0856-1748
FU National Institutes of Health (NIH) [RO1 AI 075416-01, 5R03TW007966-02];
DFW; National Institute of Allergy and Infectious Diseases (NIAID);
Conselho Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq)
[470570/2006-7]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(FAPESP) [05/51988-0, 07/51199-0]
FX This research was supported by funds from the National Institutes of
Health (NIH) grants RO1 AI 075416-01 to MUF and 5R03TW007966-02 to NK
and DFW, the Intramural Research Program of the National Institute of
Allergy and Infectious Diseases (NIAID), NIH, to RMF, the Conselho
Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq) grant
470570/2006-7 to MUF, and the Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo (FAPESP) grants 05/51988-0 and 07/51199-0 to MUF. POS, NSS and
MUF receive or received scholarships from CNPq and MdSN, KKGS and RMG
receive or received scholarships from FAPESP. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. We thank the patients from all field
sites for their enthusiastic cooperation, the field work collaborators
Rosely S. Malafronte and Adamilson Luis de Souza for their support in
Brazil, Suon Seila and Sreng Sokunthea for their support in Cambodia,
and H. Van Thien for his support in Vietnam, Maria Jose Menezes, Melissa
da Silva Bastos and Michelle Cristina Brandi (University of Sao Paulo,
Brazil) for excellent laboratory support, Apua Paquola for help in
computational analyses and Cassiano Nunes Pereira for artwork.
NR 58
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U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD JUL 13
PY 2010
VL 11
AR 65
DI 10.1186/1471-2156-11-65
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 632CL
UT WOS:000280397700001
PM 20626846
ER
PT J
AU Freedman, JE
Larson, MG
Tanriverdi, K
O'Donnell, CJ
Morin, K
Hakanson, AS
Vasan, RS
Johnson, AD
Iafrati, MD
Benjamin, EJ
AF Freedman, Jane E.
Larson, Martin G.
Tanriverdi, Kahraman
O'Donnell, Christopher J.
Morin, Kristine
Hakanson, Amanda S.
Vasan, Ramachandran S.
Johnson, Andrew D.
Iafrati, Mark D.
Benjamin, Emelia J.
TI Relation of Platelet and Leukocyte Inflammatory Transcripts to Body Mass
Index in the Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE genes; epidemiology; leukocytes; platelets
ID GENE-EXPRESSION PROFILES; GENOME-WIDE ASSOCIATION; PERIPHERAL-BLOOD;
CELLS; PATTERNS; DISEASES; HUMANS; AORTA
AB Background-Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported.
Methods and Results-On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes. A multivariable stepwise regression model was used to assess clinical correlates of quantitative RNA expression. For specific inflammatory platelet-derived transcripts, including ICAM1, IFNG, IL1R1, IL6, MPO, COX2, TNF, TLR2, and TLR4, there were significant associations with higher body mass index (BMI). Compared with platelets, fewer leukocyte-derived transcripts were associated with BMI or other cardiovascular risk factors. Select transcripts were found to be highly heritable, including GPIBA and COX1. Almost uniformly, heritable transcripts were not those associated with BMI.
Conclusions-Inflammatory transcripts derived from platelets, particularly those part of the nuclear factor kappa B pathway, are associated with BMI, whereas others are heritable. This is the first study, using a large community-based cohort, to demonstrate clinical correlates of gene expression and is consistent with the hypothesis that specific peripheral-blood transcripts play a role in the pathogenesis of coronary heart disease and its risk factors. (Circulation. 2010; 122: 119-129.)
C1 [Freedman, Jane E.] Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA 02118 USA.
[Hakanson, Amanda S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Iafrati, Mark D.] Tufts Med Ctr, Div Vasc Surg, Boston, MA USA.
[Larson, Martin G.; O'Donnell, Christopher J.; Hakanson, Amanda S.; Vasan, Ramachandran S.; Johnson, Andrew D.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Freedman, JE (reprint author), Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Inst, 700 Albany St,W-507, Boston, MA 02118 USA.
EM freedmaj@bu.edu
RI Johnson, Andrew/G-6520-2013;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU [N01-HC 25195]; [HL087201]; [HL092577-01A1]; [HL076784]; [AG028321]
FX The Framingham Heart Study is supported by N01-HC 25195; this work was
also supported by HL087201 (Dr Freedman) and HL092577-01A1, HL076784,
and AG028321 (Dr Benjamin).
NR 33
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 13
PY 2010
VL 122
IS 2
BP 119
EP U52
DI 10.1161/CIRCULATIONAHA.109.928192
PG 25
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 624FI
UT WOS:000279801700004
PM 20606121
ER
PT J
AU Chen, C
Yang, SL
Chen, FQ
Ni, L
Ma, F
Lin, F
Xiao, XA
Zeldin, DC
Wang, DW
AF Chen, Chen
Yang, Shenglan
Chen, Fuqiong
Ni, Li
Ma, Fei
Lin, Fan
Xiao, Xiao
Zeldin, Darryl C.
Wang, Dao Wen
TI MiR-21*Exhibits Cardiovascular Protection in Chronic Heart Failure by
Targeting MYBPC3
SO CIRCULATION
LA English
DT Meeting Abstract
CT World Congress of Cardiology Scientific Sessions
CY JUN 16-19, 2010
CL Beijing, PEOPLES R CHINA
C1 [Chen, Chen; Yang, Shenglan; Chen, Fuqiong; Ni, Li; Ma, Fei; Lin, Fan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430074, Peoples R China.
[Chen, Chen; Yang, Shenglan; Chen, Fuqiong; Ni, Li; Ma, Fei; Lin, Fan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Gene Therapy Ctr, Wuhan 430074, Peoples R China.
[Xiao, Xiao] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA.
[Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
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U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 13
PY 2010
VL 122
IS 2
MA P102
BP E132
EP E132
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 624FI
UT WOS:000279801702081
ER
PT J
AU Zhang, X
Khan, M
Orosz, A
Zhang, HL
Scott, L
Davidson, C
Soorappan, R
Wang, XH
Litwin, S
Benjamin, I
AF Zhang, Xiu
Khan, Muhammad
Orosz, Andras
Zhang, Huali
Scott, Lensey
Davidson, Chris
Soorappan, Raj
Wang, Xiaohui
Litwin, Sheldon
Benjamin, Ivor
TI Activation of Heat Shock Factor 1 by Doxycycline in rtTA/caHSF1
Transgenic Mouse Reduces Cardiac Injury Caused by Ischemia Reperfusion
SO CIRCULATION
LA English
DT Meeting Abstract
CT World Congress of Cardiology Scientific Sessions
CY JUN 16-19, 2010
CL Beijing, PEOPLES R CHINA
C1 [Zhang, Xiu; Khan, Muhammad; Zhang, Huali; Scott, Lensey; Davidson, Chris; Soorappan, Raj; Wang, Xiaohui; Litwin, Sheldon; Benjamin, Ivor] Univ Utah, Salt Lake City, UT USA.
[Orosz, Andras] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 13
PY 2010
VL 122
IS 2
MA 0424
BP E99
EP E99
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 624FI
UT WOS:000279801701383
ER
PT J
AU Sheehan, FT
AF Sheehan, Frances T.
TI The instantaneous helical axis of the subtalar and talocrural joints: a
non-invasive in vivo dynamic study
SO JOURNAL OF FOOT AND ANKLE RESEARCH
LA English
DT Article
ID ANKLE JOINT; COMPUTED-TOMOGRAPHY; KINEMATICS; PHASE; KNEE; MRI;
STANDARDIZATION; ARTHROPLASTY; MOBILITY; COMPLEX
AB Background: An understanding of rear-foot (talocrural and subtalar joints) kinematics is critical for diagnosing foot pathologies, designing total ankle implants, treating rear-foot injuries and quantifying gait abnormalities. The majority of kinematic data available have been acquired through static cadaver work or passive in vivo studies. The applicability of these data to dynamic in vivo situations remains unknown. Thus, the purpose of this study was to fully quantify subtalar, talocrural and calcaneal-tibial in vivo kinematics in terms of the instantaneous helical axis (IHA) in twenty-five healthy ankles during a volitional activity that simulated single-leg toe-raises with partial-weight support, requiring active muscle control.
Methods: Subjects were each placed supine in a 1.5 T MRI and asked to repeat this simulated toe-raise while a full sagittal-cine-phase contrast (dynamic) MRI dataset was acquired. From the cine-phase contrast velocity a full kinematic description for each joint was derived.
Results: Nearly all motion quantified at the calcaneal-tibial joint was attributable to the talocrural joint. The subtalar IHA orientation and position were highly variable; whereas, the talocrural IHA orientation and position were extremely consistent.
Conclusion: The talocrural was well described by the IHA and could be modeled as a fixed-hinge joint, whereas the subtalar could not be.
C1 NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Sheehan, FT (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bldg 10, Bethesda, MD 20892 USA.
EM fsheehan@cc.nih.gov
RI sheehan, frances/B-6962-2009
FU International Foot and Ankle Biomechanics meeting (iFAB) in Bologna;
Diagnostic Radiology Department at the National Institutes of Health;
NIH (CC); NIH (NICHD)
FX A presentation based on this work won the Best Paper Award at the 2008
International Foot and Ankle Biomechanics meeting (iFAB) in Bologna. I
wish to thank Andrea R. Seisler and Tracy Rausch for the assistance in
device design & fabrication along with data collection. I would like to
thank Steven Stanhope, PhD, for guidance throughout the project. I would
also like to thank Bonnie Damaska, Jamie Fraunhaffer, Jere McLucas and
the Diagnostic Radiology Department at the National Institutes of Health
for their support and research time. Any opinions, findings, and
conclusions or recommendations expressed in this material are those of
the author and do not necessarily reflect the views of the National
Institutes of Health or the US Public Health Service. This research was
supported in part by the Intramural Research Program of the NIH, (CC and
NICHD).
NR 34
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U1 3
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-1146
J9 J FOOT ANKLE RES
JI J. Foot Ankle Res.
PD JUL 13
PY 2010
VL 3
AR 13
DI 10.1186/1757-1146-3-13
PG 10
WC Orthopedics
SC Orthopedics
GA 838WG
UT WOS:000296323600001
PM 20626876
ER
PT J
AU Cannon, RO
AF Cannon, Richard O., III
TI Coronary Slow-Flow Phenomenon or Syndrome Y A Microvascular Angina
Awaiting Recognition Reply
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
C1 NHLBI, NIH, Translat Med Branch, Bethesda, MD 20892 USA.
RP Cannon, RO (reprint author), NHLBI, NIH, Translat Med Branch, Bldg 10-CRC,Room 5-3330 10 Ctr Dr, Bethesda, MD 20892 USA.
EM cannonr@nih.gov
NR 2
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 13
PY 2010
VL 56
IS 3
BP 240
EP 240
DI 10.1016/j.jacc.2009.11.100
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 620SO
UT WOS:000279520200013
ER
PT J
AU Schellinger, PD
Bryan, RN
Caplan, LR
Detre, JA
Edelman, RR
Jaigobin, C
Kidwell, CS
Mohr, JP
Sloan, M
Sorensen, AG
Warach, S
AF Schellinger, P. D.
Bryan, R. N.
Caplan, L. R.
Detre, J. A.
Edelman, R. R.
Jaigobin, C.
Kidwell, C. S.
Mohr, J. P.
Sloan, M.
Sorensen, A. G.
Warach, S.
TI Evidence-based guideline: The role of diffusion and perfusion MRI for
the diagnosis of acute ischemic stroke Report of the Therapeutics and
Technology Assessment Subcommittee of the American Academy of Neurology
SO NEUROLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN ACTIVATOR; SUSPECTED ACUTE STROKE; OF-HEALTH STROKE;
THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; HYPERACUTE STROKE;
INTRACEREBRAL HEMORRHAGE; CEREBRAL-ISCHEMIA; CT; VOLUME
AB Objective: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke.
Methods: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI.
Results and Recommendations: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U). Neurology(R) 2010;75:177-185
C1 [Schellinger, P. D.; Warach, S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Schellinger, P. D.] Univ Erlangen Nurnberg, Dept Neurol, D-8520 Erlangen, Germany.
[Detre, J. A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Bryan, R. N.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Caplan, L. R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Edelman, R. R.] Northwestern Univ, Dept Radiol, Evanston, IL USA.
[Jaigobin, C.] Toronto Gen Hosp, Div Neurol, Toronto, ON, Canada.
[Kidwell, C. S.] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Mohr, J. P.] Columbia Univ, New York, NY USA.
[Sloan, M.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA.
[Sorensen, A. G.] MGH, Dept Radiol, Boston, MA USA.
RP Schellinger, PD (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA.
EM guidelines@aan.com
RI Bryan, R. Nick/P-1661-2014
FU NCI NIH HHS [CA137254]; NCRR NIH HHS [P41RR002305]; NHLBI NIH HHS
[N01-HC-95178, R01 HL102119]; NIA NIH HHS [R01AG034682]; NICHD NIH HHS
[R24 HD050836, R24 HD050838, R24HD050836]; NIDA NIH HHS [R03 DA027098,
R21DA025882]; NIDDK NIH HHS [R01 DK085615]; NIMH NIH HHS [R01MH080729];
NINDS NIH HHS [K24 NS058386, P30 NS045839, R01 NS060653, R01 NS061572,
R01 NS063925, R01NS057400, R01NS063925, R01NS38477, R21NS061119,
T32NS054575]
NR 40
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U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 13
PY 2010
VL 75
IS 2
BP 177
EP 185
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 628GW
UT WOS:000280103900014
PM 20625171
ER
PT J
AU Berezhkovskii, AM
Barzykin, AV
AF Berezhkovskii, A. M.
Barzykin, A. V.
TI Extended narrow escape problem: Boundary homogenization-based analysis
SO PHYSICAL REVIEW E
LA English
DT Article
ID PERIODIC POROUS MATERIALS; CELL-CULTURES; PART I; DIFFUSION;
MICRODOMAINS; EIGENVALUE; AUTOCRINE; MEMBRANE; SURFACES; DOMAINS
AB Diffusion of particles in confined domains with absorbing spots on the otherwise reflecting boundaries is ubiquitous in nature and technology. Because of nonuniform boundary conditions, the problem of finding the mean first passage time (MFPT) of the particle to one of the spots is extremely complicated. We show how the difficulties can be overcome by means of boundary homogenization when the domain is a circular disk whose boundary contains n nonoverlapping identical absorbing arcs, which may occupy an arbitrary fraction of the boundary. We find the MFPT as a function of the fraction of the boundary occupied by the arcs (i) for n evenly spaced arcs and (ii) for two arcs arbitrarily located on the boundary. As the arc length tends to zero, our approximate solution reduces to the known asymptotic formula for the MFPT rigorously derived in studies devoted of the narrow escape problem.
C1 [Berezhkovskii, A. M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Barzykin, A. V.] Royal Bank Scotland, London EC2M 4AA, England.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
FU NIH, Center for Information Technology
FX We are grateful to Yurii Makhnovskii, Stas Shvartsman, and Vladimir
Zitserman for useful discussions. A.M.B. was supported by the Intramural
Research Program of the NIH, Center for Information Technology.
NR 39
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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 JUL 13
PY 2010
VL 82
IS 1
AR 011114
DI 10.1103/PhysRevE.82.011114
PN 1
PG 5
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 624LK
UT WOS:000279819900003
PM 20866572
ER
PT J
AU Steer, CD
Smith, GD
Emmett, PM
Hibbeln, JR
Golding, J
AF Steer, Colin D.
Smith, George Davey
Emmett, Pauline M.
Hibbeln, Joseph R.
Golding, Jean
TI FADS2 Polymorphisms Modify the Effect of Breastfeeding on Child IQ
SO PLOS ONE
LA English
DT Article
ID FATTY-ACID-COMPOSITION; GENETIC-VARIANTS; FISH INTAKE; US COHORT;
PREGNANCY; N-3; CLUSTER; MILK; PHOSPHOLIPIDS; EPIDEMIOLOGY
AB Background: Breastfeeding is important for child cognitive development. A study by Caspi et al has suggested that rs174575 within the FADS2 gene moderates this effect so that children homozygous in the minor allele (GG genotype) have similar IQs irrespective of feeding method.
Methods and Principal Findings: In our study of 5934 children aged 8 years, no genetic main effect with IQ was found for rs174575. However, an interaction with this polymorphism was observed such that breastfed GG children performed better than their formula fed counterparts by an additional 5.8 points [1.4, 10.1] (interaction p = 0.0091). Interaction results were attenuated by about 10% after adjustment for 7 factors. This study also investigated rs1535, another FADS2 polymorphism in linkage disequilibrium with rs174575, together with performance and verbal IQ, finding similar results although effect sizes were generally reduced.
Conclusions and Significance: This study did not replicate the findings of Caspi et al. In contrast to their study, GG children exhibited the greatest difference between feeding methods such that breastfed children performed similarly irrespective of child genotype whereas formula fed GG children performed worse than other children on formula milk. Further studies are required to replicate these findings.
C1 [Steer, Colin D.; Emmett, Pauline M.; Golding, Jean] Univ Bristol, Dept Community Based Med, Ctr Child & Adolescent Hlth, Bristol, Avon, England.
[Smith, George Davey] Univ Bristol, MRC, Ctr Causal Analyses Translat Epidemiol, Bristol, Avon, England.
[Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD USA.
RP Steer, CD (reprint author), Univ Bristol, Dept Community Based Med, Ctr Child & Adolescent Hlth, Bristol, Avon, England.
EM Colin.Steer@bristol.ac.uk
RI Davey Smith, George/A-7407-2013;
OI Davey Smith, George/0000-0002-1407-8314; Monsalve, Beatriz
Elena/0000-0002-5994-866X; Emmett, Pauline/0000-0003-1076-4779; Golding,
Jean/0000-0003-2826-3307
FU National Oceanic and Atmospheric Administration; Waterloo Foundation; UK
Medical Research Council; Wellcome Trust; University of Bristol
FX National Oceanic and Atmospheric Administration and the Waterloo
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.; We are
extremely grateful to all the families who took part in this study, the
midwives for their help in recruiting them, and the whole ALSPAC team,
which includes interviewers, computer and laboratory technicians,
clerical workers, research scientists, volunteers, managers,
receptionists and nurses. The UK Medical Research Council, the Wellcome
Trust and the University of Bristol currently provide core support for
ALSPAC. This publication is the work of the authors and Colin Steer and
Jean Golding will serve as guarantors for the contents of this paper.
NR 36
TC 41
Z9 42
U1 0
U2 20
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 JUL 13
PY 2010
VL 5
IS 7
AR e11570
DI 10.1371/journal.pone.0011570
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 624MG
UT WOS:000279822300020
PM 20644632
ER
PT J
AU Raz-Prag, D
Grimes, WN
Fariss, RN
Vijayasarathy, C
Campos, MM
Bush, RA
Diamond, JS
Sieving, PA
AF Raz-Prag, Dorit
Grimes, William N.
Fariss, Robert N.
Vijayasarathy, Camasamudram
Campos, Maria M.
Bush, Ronald A.
Diamond, Jeffrey S.
Sieving, Paul A.
TI Probing potassium channel function in vivo by intracellular delivery of
antibodies in a rat model of retinal neurodegeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Kir; peptide carrier; Pep-1; retinal bipolar cells; Muller cells
ID PROTEIN-KINASE-C; SCOTOPIC THRESHOLD RESPONSE; ADAPTED CAT RETINA; ROD
BIPOLAR CELLS; RCS RAT; MULLER CELLS; VERTEBRATE RETINA; NEGATIVE
RESPONSE; PROXIMAL PORTION; GLIAL-CELLS
AB Inward rectifying potassium (Kir) channels participate in regulating potassium concentration (K(+)) in the central nervous system (CNS), including in the retina. We explored the contribution of Kir channels to retinal function by delivering Kir antibodies (Kir-Abs) into the rat eye in vivo to interrupt channel activity. Kir-Abs were coupled to a peptide carrier to reach intracellular epitopes. Functional effects were evaluated by recording the scotopic threshold response (STR) and photopic negative response (PhNR) of the electroretinogram (ERG) noninvasively with an electrode on the cornea to determine activity of the rod and cone pathways, respectively. Intravitreal delivery of Kir2.1-Ab coupled to the peptide carrier diminished these ERG responses equivalent to dimming the stimulus 10- to 100-fold. Immunohistochemistry (IHC) showed Kir2.1 immunostaining of retinal bipolar cells (BCs) matching the labeling pattern obtained with conventional IHC of applying Kir2.1-Ab to fixed retinal sections postmortem. Whole-cell voltage-clamp BC recordings in rat acute retinal slices showed suppression of barium-sensitive Kir2.1 currents upon inclusion of Kir2.1-Ab in the patch pipette. The in vivo functional and structural results implicate a contribution of Kir2.1 channel activity in these electronegative ERG potentials. Studies with Kir4.1-Ab administered in vivo also suppressed the ERG components and showed immunostaining of Muller cells. The strategy of administering Kir antibodies in vivo, coupled to a peptide carrier to facilitate intracellular delivery, identifies roles for Kir2.1 and Kir4.1 in ERG components arising in the proximal retina and suggests this approach could be of further value in research.
C1 [Raz-Prag, Dorit; Vijayasarathy, Camasamudram; Bush, Ronald A.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD 20892 USA.
[Grimes, William N.; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Fariss, Robert N.; Campos, Maria M.] NIH, Biol Imaging Core Facil, Bethesda, MD 20892 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sieving, PA (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD 20892 USA.
EM paulsieving@nei.nih.gov
RI Diamond, Jeffrey/C-1835-2015
OI Diamond, Jeffrey/0000-0002-1770-2629
FU National Institute on Deafness and Other Communication Disorders;
National Eye Institute; National Institute of Neurological Disease and
Stroke
FX We thank Laura J. Frishman for helpful discussions. The work was
supported by the National Institutes of Health Intramural Research
Programs of the National Institute on Deafness and Other Communication
Disorders, the National Eye Institute, and the National Institute of
Neurological Disease and Stroke.
NR 56
TC 13
Z9 13
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 13
PY 2010
VL 107
IS 28
BP 12710
EP 12715
DI 10.1073/pnas.0913472107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 624TD
UT WOS:000279843200057
PM 20616020
ER
PT J
AU Llewellyn, DJ
Lang, IA
Langa, KM
Muniz-Terrera, G
Phillips, CL
Cherubini, A
Ferrucci, L
Melzer, D
AF Llewellyn, David J.
Lang, Iain A.
Langa, Kenneth M.
Muniz-Terrera, Graciela
Phillips, Caroline L.
Cherubini, Antonio
Ferrucci, Luigi
Melzer, David
TI Vitamin D and Risk of Cognitive Decline in Elderly Persons
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID SERUM 25-HYDROXYVITAMIN-D LEVELS; RANDOMIZED CONTROLLED-TRIALS; D
SUPPLEMENTATION; OLDER-ADULTS; D DEFICIENCY; PARATHYROID-HORMONE;
ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; UNITED-STATES; DEMENTIA
AB Background: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia.
Methods: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH] D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing.
Results: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25 (OH) D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH) D (>= 75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH) D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH) D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH) D deficient compared with those with sufficient levels of 25(OH) D. No significant association was observed for Trail-Making Test A.
Conclusion: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.
C1 [Llewellyn, David J.; Lang, Iain A.; Melzer, David] Univ Exeter, Peninsula Med Sch, Publ Hlth & Epidemiol Grp, Exeter EX2 5DW, Devon, England.
[Langa, Kenneth M.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Langa, Kenneth M.] Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor, MI USA.
[Muniz-Terrera, Graciela] MRC, Biostat Unit, Cambridge CB2 2BW, England.
[Phillips, Caroline L.; Ferrucci, Luigi] NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA.
[Cherubini, Antonio] Perugia Univ Hosp & Med Sch, Inst Gerontol & Geriatr, Perugia, Italy.
RP Llewellyn, DJ (reprint author), Univ Exeter, Royal Devon & Exeter Hosp, Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.llewellyn@pms.ac.uk
RI Lang, Iain/B-8255-2008;
OI Lang, Iain/0000-0002-8473-2350; Cherubini, Antonio/0000-0003-0261-9897;
Melzer, David/0000-0002-0170-3838
FU Italian Ministry of Health; United States National Institute on Aging
(NIA); NIA [R01 AG027010]; National Health Service; MRC
FX The InCHIANTI study is supported in part by the Italian Ministry of
Health and by the United States National Institute on Aging (NIA). Dr
Langa was supported by NIA grant R01 AG027010. Dr Lang is an Academic
Speciality Registrar in Public Health supported by the National Health
Service South-West Region Public Health Training Scheme. Dr
Muniz-Terrera is funded by an MRC Career Development Award in
Biostatistics.
NR 40
TC 192
Z9 201
U1 5
U2 29
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 JUL 12
PY 2010
VL 170
IS 13
BP 1135
EP 1141
DI 10.1001/archinternmed.2010.173
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624DY
UT WOS:000279797700010
PM 20625021
ER
PT J
AU Honig, D
DeRouchey, J
Jungmann, R
Koch, C
Plank, C
Radler, JO
AF Hoenig, Daniel
DeRouchey, Jason
Jungmann, Ralf
Koch, Christian
Plank, Christian
Raedler, Joachim O.
TI Biophysical Characterization of Copolymer-Protected Gene Vectors
SO BIOMACROMOLECULES
LA English
DT Article
ID CROSS-CORRELATION SPECTROSCOPY; FLUORESCENCE CORRELATION SPECTROSCOPY;
IN-VIVO; NONVIRAL VECTORS; TRANSFECTION EFFICIENCY; FORCE MICROSCOPE;
THERAPY PROGRESS; DNA POLYPLEXES; PEI COMPLEXES; PROTON SPONGE
AB A copolymer-protected gene vector (COPROG) is a three-component gene delivery system consisting of a preformed DNA and branched polyethylenimine (bPEI) complex subsequently modified by the addition of a copolymer (P6YE5C) incorporating both poly(ethylene glycol) (PEG) and anionic peptides. Using fluorescence correlation spectroscopy (FCS) and atomic force microscopy (AFM), we characterized and compared the self-assembly of bPEI/DNA particles and COPROG complexes. In low salt buffer, both bPEI/DNA and COPROG formulations form stable nanoparticles with hydrodynamic radii between 60-120 nm. COPROG particles, as compared to bPEI/DNA, show greatly improved particle stability to both physiological salt as well as low pH conditions. Binding stoichiometry of the three-component COPROG system was investigated by dual-color fluorescence cross-correlation spectroscopy (FCCS). It was found that a significant fraction of P6YE5C copolymer aggregates with excess bPEI forming bPEI/P6YE5C "ghost complexes" with no DNA inside. The ratio of ghost particles to COPROG complexes is about 4: I. In addition, we find a large fraction of excess P6YE5C copolymer, which remains unbound in solution. We observe a 2-4-fold enhanced reporter gene expression with COPROG formulations at various equivalents as compared to bPEI-DNA alone. We believe that both complex stabilization as well as the capture of excess bPEI into ghost particles induced by the copolymer is responsible for the improvement in gene expression.
C1 [DeRouchey, Jason] NICHHD, Program Phys Biol, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA.
[Hoenig, Daniel; Raedler, Joachim O.] Univ Munich, Soft Condensed Matter Grp, D-80539 Munich, Germany.
[Jungmann, Ralf] Tech Univ Munich, D-85748 Garching, Germany.
[Koch, Christian; Plank, Christian] Tech Univ Munich, Inst Expt Oncol, D-81675 Munich, Germany.
RP DeRouchey, J (reprint author), NICHHD, Program Phys Biol, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA.
EM deroucja@mail.nih.gov; joachim.raedler@physik.uni-muenchen.de
RI DeRouchey, Jason/C-5907-2011; Plank, Christian/F-9628-2011; Jungmann,
Ralf/A-6357-2015
OI DeRouchey, Jason/0000-0002-3624-4432; Jungmann, Ralf/0000-0003-4607-3312
FU German Federal Ministry of Education and Research; Nanosystems
Initiative Munich; BMBF [0312019A]; ESF; Elite Network of Bavaria
(IDK-CompInt); Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health
FX The authors thank F. C. Simmel and the Physics of Biomolecular Systems
and Bionanotechnology Laboratory for use of the AFM. Funding by the
German Federal Ministry of Education and Research as well as by
Nanosystems Initiative Munich is gratefully acknowledged. J.O.R. and
C.P. acknowledge funding through BMBF Project 0312019A. J.O.R. also
acknowledges a travel fund by the ESF. J.D. was supported in part by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health. R.J. was supported by the Elite Network of Bavaria
(IDK-CompInt).
NR 43
TC 10
Z9 11
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD JUL 12
PY 2010
VL 11
IS 7
BP 1802
EP 1809
DI 10.1021/bm1002569
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 622QS
UT WOS:000279679300015
PM 20672861
ER
PT J
AU Schwander, M
Kachar, B
Muller, U
AF Schwander, Martin
Kachar, Bechara
Mueller, Ulrich
TI The cell biology of hearing
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID OUTER HAIR-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; SYNDROME TYPE IIA;
MYOSIN-VIIA GENE; USHER-SYNDROME PROTEINS; COCHLEAR SENSORY CELLS;
ACTIN-BUNDLING PROTEIN; ANKLE-LINK COMPLEX; INNER-EAR; TIP-LINK
AB Mammals have an astonishing ability to sense and discriminate sounds of different frequencies and intensities. Fundamental for this process are mechanosensory hair cells in the inner ear that convert sound-induced vibrations into electrical signals. The study of genes that are linked to deafness has provided insights into the cell biological mechanisms that control hair cell development and their function as mechanosensors.
C1 [Schwander, Martin; Mueller, Ulrich] Scripps Res Inst, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
[Schwander, Martin; Mueller, Ulrich] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
[Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
RP Muller, U (reprint author), Scripps Res Inst, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
EM umueller@scripps.edu
FU NIDCD [DC007704, DC005965]; NIDCD Division of Intramural Research;
Skaggs Institute for Chemical Biology; Dorris Neuroscience Center
FX This work was funded by NIDCD grants DC007704 and DC005965 (to U.
Muller), NIDCD Division of Intramural Research (to B. Kachar), the
Skaggs Institute for Chemical Biology (to U. Muller), and the Dorris
Neuroscience Center (to U. Muller).
NR 152
TC 106
Z9 108
U1 3
U2 31
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 JUL 12
PY 2010
VL 190
IS 1
BP 9
EP 20
DI 10.1083/jcb.201001138
PG 12
WC Cell Biology
SC Cell Biology
GA 624CC
UT WOS:000279792700004
PM 20624897
ER
PT J
AU Kim, SC
Becker, S
Dieffenbach, C
Hanewall, BS
Hankins, C
Lo, YR
Mellors, JW
O'Reilly, K
Paxton, L
Roffenbender, JS
Warren, M
Piot, P
Dybul, MR
AF Kim, Susan C.
Becker, Stephen
Dieffenbach, Carl
Hanewall, Blair S.
Hankins, Catherine
Lo, Ying-Ru
Mellors, John W.
O'Reilly, Kevin
Paxton, Lynn
Roffenbender, Jason S.
Warren, Mitchell
Piot, Peter
Dybul, Mark R.
TI Planning for pre-exposure prophylaxis to prevent HIV transmission:
challenges and opportunities
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Editorial Material
ID INFECTION; AFRICA
AB There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting.
C1 [Kim, Susan C.; Roffenbender, Jason S.; Dybul, Mark R.] Georgetown Univ, ONeill Inst Natl & Global Hlth Law, Washington, DC 20057 USA.
[Becker, Stephen; Hanewall, Blair S.] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Dieffenbach, Carl] NIAID, Washington, DC USA.
[Hankins, Catherine] Joint United Nations Programme HIV AIDS, Geneva, Switzerland.
[Lo, Ying-Ru; O'Reilly, Kevin] World Hlth Org, Geneva, Switzerland.
[Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA.
[Paxton, Lynn] Ctr Dis Control & Prevent, Washington, DC USA.
[Warren, Mitchell] AIDS Vaccine Advocacy Coalit, New York, NY USA.
[Piot, Peter] Univ London Imperial Coll Sci Technol & Med, Inst Global Hlth, London, England.
[Dybul, Mark R.] George W Bush Inst, Dallas, TX USA.
RP Kim, SC (reprint author), Georgetown Univ, ONeill Inst Natl & Global Hlth Law, Washington, DC 20057 USA.
EM sck3@law.georgetown.edu
OI Hankins, Catherine/0000-0002-1642-8592
FU PHS HHS [1U01A 1068633]
NR 25
TC 32
Z9 34
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL 12
PY 2010
VL 13
AR 24
DI 10.1186/1758-2652-13-24
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 839CO
UT WOS:000296342500001
PM 20624303
ER
PT J
AU Aid, S
Parikh, N
Palumbo, S
Bosetti, F
AF Aid, Saba
Parikh, Nishant
Palumbo, Sara
Bosetti, Francesca
TI Neuronal overexpression of cyclooxygenase-2 does not alter the
neuroinflammatory response during brain innate immune activation
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Cyclooxygenase-2; Microglia; Neuron; Neuroinflammation; Cytokines;
Lipopolysaccharide
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; TRANSGENIC
MICE; INDUCIBLE CYCLOOXYGENASE; GENE-EXPRESSION; NEURODEGENERATION;
LIPOPOLYSACCHARIDE; INHIBITION; DEFICIENT; MICROGLIA
AB Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases and cyclooxygenases (COX)-1 and -2 are key regulators of innate immune responses. We recently demonstrated that COX-1 deletion attenuates, whereas COX-2 deletion enhances, the neuroinflammatory response, blood-brain barrier permeability and leukocyte recruitment during lipopolysaccharide (LPS)-induced innate immune activation. Here, we used transgenic mice, which overexpressed human COX-2 via neuron-specific Thy-1 promoter (TgCOX-2), causing elevated prostaglandins (PGs) levels. We tested whether neuronal COX-2 overexpression affects the glial response to a single intracerebroventricular injection of LPS, which produces a robust neuroinflammatory reaction. Relative to non-transgenic controls (NTg). 7 month-old TgCOX-2 did not show any basal neuroinflammation, as assessed by gene expression of markers of inflammation and oxidative stress, neuronal damage, as assessed by Fluoro-jadeB staining, or systemic inflammation, as assessed by plasma levels of IL-1 beta and corticosterone. Twenty-four hours after LPS injection, all mice showed increased microglial activation, as indicated by Iba1 immunostaining, neuronal damage, mRNA expression of cytokines (TNF-alpha, IL-6), reactive oxygen expressing enzymes (iNOS and NADPH oxidase subunits), endogenous COX-2, cPLA(2) and mPGES-1, and hippocampal and cortical IL-1 beta levels. However, the increases were similar in TgCOX-2 and NTg. In NTg, LPS increased brain PGE(2) to the levels observed in TgCOX-2. These results suggest that PGs derived from neuronal COX-2 do not play a role in the neuroinflammatory response to acute activation of brain innate immunity. This is likely due to the direct effect of LPS on glial rather than neuronal cells. Published by Elsevier Ireland Ltd.
C1 [Aid, Saba; Parikh, Nishant; Palumbo, Sara; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
RI palumbo, sara/B-1603-2013
OI palumbo, sara/0000-0002-3809-6058
FU National Institute on Aging, National Institutes of Health
FX We thank Dr. Katrin Andreasson for providing breeding pairs for the
TgCOX-2 and NTg mice. This work was entirely supported by the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health.
NR 41
TC 6
Z9 7
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD JUL 12
PY 2010
VL 478
IS 3
BP 113
EP 118
DI 10.1016/j.neulet.2010.04.076
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 620UK
UT WOS:000279525700001
PM 20451580
ER
PT J
AU Liao, CZ
Nicklaus, MC
AF Liao, Chenzhong
Nicklaus, Marc C.
TI Tautomerism and Magnesium Chelation of HIV-1 Integrase Inhibitors: A
Theoretical Study
SO CHEMMEDCHEM
LA English
DT Article
DE chelates; density functional calculations; HIV-1 integrase; inhibitors;
tautomerism
ID BETA-DIKETO ACIDS; CRYSTAL-STRUCTURES; STRAND TRANSFER; ACTIVE-SITE;
DRUG DESIGN; VIRAL-DNA; BINDING; MODEL; MECHANISM
AB The tautomerism and corresponding transition states of four authentic HIV-1 integrase (IN) inhibitor prototype structures, alpha,gamma-diketo acid, alpha,gamma-diketotriazole, dihydroxypyrimidine carboxamide and 4-quinolone-3-carboxylic acid, were investigated at the B3LYP/6-311 + + G(d,p) level in vacuum and in aqueous solvent models. To study the possible chelating modes of these tautomers with two magnesium ions-a process important for inhibition-we modeled an assembly of three formic acids, four water molecules and two Mg(2+) ions as a template mimicking the binding site of IN. The DFT calculation results show that deprotonated enolized or phenolic hydroxy groups of specific tautomers in water lead to the most stable complexes, with the two magnesium ions separated by a distance of approximately 3.70 to 3.74 angstrom, and with each magnesium ion at the center of an octahedron., The drug candidate GS-9137 (Gilead), based on the 4-quinolone-3-carboxylic acid scaffold, and its analogues form similar but different chelating modes. When one Water molecule in the complex is replaced by a methanol molecule, which mimics the terminal 3'-OH of viral DNA, a good chelating complex is retained. This supports the hypothesis that, in the binding site of IN after 3'-processing, the terminal-3'-OH of viral DNA interacts with one Mg(2+) by chelation.
C1 [Liao, Chenzhong; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS NCI Frederick, Frederick, MD 21702 USA.
RP Liao, CZ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS NCI Frederick, 376 Boyles St, Frederick, MD 21702 USA.
EM mn1@helix.nih.gov
RI Nicklaus, Marc/N-4183-2014;
OI Nicklaus, Marc/0000-0002-4775-7030
FU Intramural NIH HHS [Z01 BC010524-05]
NR 40
TC 9
Z9 9
U1 0
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD JUL 10
PY 2010
VL 5
IS 7
BP 1053
EP 1066
DI 10.1002/cmdc.201000039
PG 14
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 629GM
UT WOS:000280183300008
PM 20533499
ER
PT J
AU Truog, RD
Miller, FG
AF Truog, Robert D.
Miller, Franklin G.
TI Counterpoint: Are Donors After Circulatory Death Really Dead, and Does
It Matter? No and Not Really
SO CHEST
LA English
DT Editorial Material
C1 [Truog, Robert D.] Childrens Hosp, MSICU Off, Div Crit Care Med, Dept Anesthesia, Boston, MA 02115 USA.
[Truog, Robert D.] Harvard Univ, Sch Med, Div Med Eth, Dept Global Hlth & Social Med, Boston, MA USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Truog, RD (reprint author), Childrens Hosp, MSICU Off, Div Crit Care Med, Dept Anesthesia, Bader 6,300 Longwood Ave, Boston, MA 02115 USA.
EM robert.truog@childrens.harvard.edu
NR 11
TC 16
Z9 16
U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL 10
PY 2010
VL 138
IS 1
BP 16
EP 18
DI 10.1378/chest.10-0657
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 625MX
UT WOS:000279900500006
PM 20605813
ER
PT J
AU Negrini, S
Zoppoli, G
Andorno, E
Picciotto, A
Indiveri, F
AF Negrini, Simone
Zoppoli, Gabriele
Andorno, Enzo
Picciotto, Antonino
Indiveri, Francesco
TI Iodized Oil Pleural Effusion in a Patient Previously Treated With
Transarterial Chemoembolization for Hepatocellular Carcinoma
SO CHEST
LA English
DT Article
ID COMPLICATIONS
AB Transarterial chemoembolization (TACE) is a nonsurgical therapeutic option for the control of hepatocellular carcinoma (HCC) in patients with cirrhosis. Although less invasive than surgical approaches, this procedure can have severe side effects, with both local and extrahepatic complications, mostly related to treatment-induced ischemic damage. Here, we describe the case of a cirrhotic female patient affected by multinodular HCC, who presented with sudden onset dyspnea and chest pain. After a thorough follow-up, her condition was found to be due to iodinized oil pleural effusion following diaphragm rupture by a fistula. This had developed from a sterile abscess formed on the site of a previously performed TACE. We discuss the differential diagnosis and the management of this case, which, to our knowledge, has never been described as a late side effect of TACE. CHEST 2010; 138(1):193-195
C1 [Negrini, Simone; Zoppoli, Gabriele; Picciotto, Antonino; Indiveri, Francesco] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy.
[Andorno, Enzo] San Martino Univ Hosp Genoa, Div Gen & Transplant Surg, Genoa, Italy.
[Zoppoli, Gabriele] Natl Canc Inst, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD USA.
RP Negrini, S (reprint author), Univ Genoa, Dept Internal Med, Vle Benedetto XV 6, I-16132 Genoa, Italy.
EM negrini@unige.it
RI Zoppoli, Gabriele/B-6935-2016;
OI Zoppoli, Gabriele/0000-0003-3890-5588; NEGRINI,
Simone/0000-0003-1267-4320
NR 5
TC 4
Z9 5
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL 10
PY 2010
VL 138
IS 1
BP 193
EP 195
DI 10.1378/chest.09-2213
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 625MX
UT WOS:000279900500031
PM 20605818
ER
PT J
AU Moody, TW
Berna, MJ
Mantey, S
Sancho, V
Ridnour, L
Wink, DA
Chan, D
Giaccone, G
Jensen, RT
AF Moody, Terry W.
Berna, Marc J.
Mantey, Samuel
Sancho, Veronica
Ridnour, Lisa
Wink, David A.
Chan, Daniel
Giaccone, Giuseppe
Jensen, Robert T.
TI Neuromedin B receptors regulate EGF receptor tyrosine phosphorylation in
lung cancer cells
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Lung cancer; Neuromedin B; Epidermal growth factor receptor;
Transactivation; Reactive oxygen species
ID GROWTH-FACTOR RECEPTOR; GASTRIN-RELEASING-PEPTIDE; MAMMALIAN BOMBESIN
RECEPTORS; SMOOTH-MUSCLE-CELLS; HIGH-AFFINITY; AUTOCRINE GROWTH; RAT-1
CELLS; NECK-CANCER; LINES; GEFITINIB
AB Neuromedin B (NMB), a member of the bombesin family of peptides, is an autocrine growth factor for many lung cancer cells. The present study investigated the ability of NMB to cause transactivation of the epidermal growth factor (EGF) receptor in lung cancer cells. By Western blot, addition of NMB or related peptides to NCI-H1299 human non-small cell lung cancer (NSCLC) cells, caused phosphorylation of Tyr(1068) of the EGF receptor. The signal was amplified using NCI-H1299 cells stably transected with NMB receptors. The transactivation of the EGF receptor or the tyrosine phosphorylation of ERK caused by NMB-like peptides was inhibited by AG1478 or gefitinib (tyrosine kinase inhibitors) and NMB receptor antagonist PD168368 but not the GRP receptor antagonist, BW2258U89. The transactivation of the EGF receptor caused by NMB-like peptides was inhibited by GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), or transforming growth factor (TGF)alpha antibody. The transactivation of the EGF receptor and the increase in reactive oxygen species caused by NMB-like peptides was inhibited by N-acetylcysteine (NAC) or Tiron. Gefitinib inhibited the proliferation of NCI-H1299 cells and its sensitivity was increased by the addition of PD168368. The results indicate that the NMB receptor regulates EGF receptor transactivation by a mechanism dependent on Src as well as metalloprotease activation and generation of reactive oxygen species. Published by Elsevier B.V.
C1 [Moody, Terry W.] NCI, Dept Hlth & Human Serv, CCR, Off Director, Bethesda, MD 20892 USA.
[Berna, Marc J.; Mantey, Samuel; Sancho, Veronica; Jensen, Robert T.] NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA.
[Ridnour, Lisa; Wink, David A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Chan, Daniel] Univ Colorado, Dept Med, Ctr Canc, Aurora, CO USA.
[Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Dept Hlth & Human Serv, CCR, Off Director, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU NIDDK, NIH; NCI, NIH
FX The authors thank Dr. N. Gonzalez for helpful discussions. This research
was partially supported by the intramural research funds of the NIDDK
and NCI, of NIH.
NR 40
TC 25
Z9 26
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD JUL 10
PY 2010
VL 637
IS 1-3
BP 38
EP 45
DI 10.1016/j.ejphar.2010.03.057
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612EF
UT WOS:000278878900006
PM 20388507
ER
PT J
AU Baker, SG
Cappuccio, A
Potter, JD
AF Baker, Stuart G.
Cappuccio, Antonio
Potter, John D.
TI Research on Early-Stage Carcinogenesis: Are We Approaching Paradigm
Instability?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID MOLECULAR-ORIGINS; SOMATIC MUTATION; CANCER; CELLS; HYPOMETHYLATION;
MORPHOSTATS; MALIGNANCY; GENES; MICE
C1 [Baker, Stuart G.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Cappuccio, Antonio] Inst Curie, Paris, France.
[Potter, John D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
OI Potter, John/0000-0001-5439-1500
NR 28
TC 26
Z9 27
U1 0
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2010
VL 28
IS 20
BP 3215
EP 3218
DI 10.1200/JCO.2010.28.5460
PG 4
WC Oncology
SC Oncology
GA 622CW
UT WOS:000279637600004
PM 20547997
ER
PT J
AU Sparano, JA
Vrdoljak, E
Rixe, O
Xu, BH
Manikhas, A
Medina, C
Da Costa, SCV
Ro, J
Rubio, G
Rondinon, M
Manga, GP
Peck, R
Poulart, V
Conte, P
AF Sparano, Joseph A.
Vrdoljak, Eduard
Rixe, Oliver
Xu, Binghe
Manikhas, Alexey
Medina, Carlos
Ventilari Da Costa, Susanne Crocamo
Ro, Jungsil
Rubio, Gonzalo
Rondinon, Monica
Perez Manga, Gumersindo
Peck, Ronald
Poulart, Valerie
Conte, Pierfranco
TI Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus
Capecitabine in Patients With Metastatic Breast Cancer Previously
Treated With an Anthracycline and a Taxane
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EPOTHILONE-B ANALOG; 1ST-LINE THERAPY; CLINICAL-TRIAL; MULTICENTER;
BMS-247550; RESISTANT; MONOTHERAPY; MECHANISMS; EFFICACY; SAFETY
AB Purpose We sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.
Patients and Methods A total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) or capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death.
Results There was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible.
Conclusion This study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.
C1 Montefiore Einstein Canc Ctr, Bronx, NY USA.
Univ Hosp Split, Ctr Oncol, Split, Croatia.
NCI, Bethesda, MD 20892 USA.
Chinese Acad Med Sci, Canc Hosp, Beijing 100037, Peoples R China.
St Petersburg City Oncol Ctr, St Petersburg, Russia.
Hosp Britan & Hosp Frances, Buenos Aires, DF, Argentina.
Interhosp III, Rio De Janeiro, Brazil.
Natl Canc Ctr, Seoul, South Korea.
Univ Gen Hosp Gregorio Maranon, Madrid, Spain.
Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
Bristol Myers Squibb Co, Braine Lalleud, Belgium.
Univ Hosp, Dept Hematol & Oncol, Modena, Italy.
RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 1825 Eastchester Rd, Bronx, NY 10461 USA.
EM jsparano@montefiore.org
RI CONTE, PIERFRANCO/F-7418-2014
OI CONTE, PIERFRANCO/0000-0002-5210-5344
FU Bristol-Myers Squibb
FX Supported by Bristol-Myers Squibb.
NR 27
TC 111
Z9 112
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 JUL 10
PY 2010
VL 28
IS 20
BP 3256
EP 3263
DI 10.1200/JCO.2009.24.4244
PG 8
WC Oncology
SC Oncology
GA 622CW
UT WOS:000279637600010
PM 20530276
ER
PT J
AU Rodriguez-Santiago, B
Malats, N
Rothman, N
Armengol, L
Garcia-Closas, M
Kogevinas, M
Villa, O
Hutchinson, A
Earl, J
Marenne, G
Jacobs, K
Rico, D
Tardon, A
Carrato, A
Thomas, G
Valencia, A
Silverman, D
Real, FX
Chanock, SJ
Perez-Jurado, LA
AF Rodriguez-Santiago, Benjamin
Malats, Nuria
Rothman, Nathaniel
Armengol, Lluis
Garcia-Closas, Montse
Kogevinas, Manolis
Villa, Olaya
Hutchinson, Amy
Earl, Julie
Marenne, Gaelle
Jacobs, Kevin
Rico, Daniel
Tardon, Adonina
Carrato, Alfredo
Thomas, Gilles
Valencia, Alfonso
Silverman, Debra
Real, Francisco X.
Chanock, Stephen J.
Perez-Jurado, Luis A.
TI Mosaic Uniparental Disomies and Aneuploidies as Large Structural
Variants of the Human Genome
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID COPY-NUMBER-VARIATION; LOW-LEVEL MOSAICISM; SOMATIC MOSAICISM;
CHROMOSOME INSTABILITY; SEGMENTAL DUPLICATIONS; HUMAN TISSUES; HUMAN
BRAIN; CANCER; HYBRIDIZATION; MECHANISMS
AB Mosaicism is defined as the coexistence of cells with different genetic composition within an individual, caused by postzygotic somatic mutation. Although somatic mosaicism for chromosomal abnormalities is a well-established cause of developmental and somatic disorders and has also been detected in different tissues, its frequency and extent in the adult normal population are still unknown. We provide here a genome-wide survey of mosaic genomic variation obtained by analyzing Illumina 1M SNP array data from blood or buccal DNA samples of 1991 adult individuals from the Spanish Bladder Cancer/EPICURO genome-wide association study. We found mosaic abnormalities in autosomes in 1.7% of samples, including 23 segmental uniparental disomies, 8 complete trisomies, and 11 large (1.5-37 Mb) copy-number variants. Alterations were observed across the different autosomes with recurrent events in chromosomes 9 and 20. No case-control differences were found in the frequency of events or the percentage of cells affected, thus indicating that most rearrangements found are not central to the development of bladder cancer. However, five out of six events tested were detected in both blood and bladder tissue from the same individual, indicating an early developmental origin. The high cellular frequency of the anomalies detected and their presence in normal adult individuals suggest that this type of mosaicism is a widespread phenomenon in the human genome. Somatic mosaicism should be considered in the expanding repertoire of inter- and intraindividual genetic variation, some of which may cause somatic human diseases but also contribute to modifying inherited disorders and/or late-onset multifactorial traits.
C1 [Rodriguez-Santiago, Benjamin; Villa, Olaya; Real, Francisco X.; Perez-Jurado, Luis A.] Univ Pompeu Fabra, Dept Ciencias Expt Salut, E-08003 Barcelona, Spain.
[Rodriguez-Santiago, Benjamin; Villa, Olaya; Perez-Jurado, Luis A.] CIBERER, E-08003 Barcelona, Spain.
[Malats, Nuria; Earl, Julie; Marenne, Gaelle; Rico, Daniel; Valencia, Alfonso; Real, Francisco X.] Ctr Nacl Invest Oncol, E-28029 Madrid, Spain.
[Rothman, Nathaniel; Garcia-Closas, Montse; Silverman, Debra; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Armengol, Lluis] qGenomics, Quantitat Genom Med Lab, E-08003 Barcelona, Spain.
[Kogevinas, Manolis] Hosp del Mar, IMIM, Municipal Inst Med Res, E-08003 Barcelona, Spain.
[Kogevinas, Manolis; Tardon, Adonina] Ctr Res Environm Epidemiol CREAL, E-08003 Barcelona, Spain.
[Kogevinas, Manolis] CIBERESP, E-08003 Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, G-11521 Athens, Greece.
[Jacobs, Kevin; Thomas, Gilles; Chanock, Stephen J.] SAIC Frederick, Core Genotyping Facil, Frederick, MD 21702 USA.
[Tardon, Adonina] Univ Oviedo, Dept Epidemiol & Med Prevent, E-33003 Oviedo, Spain.
[Carrato, Alfredo] Hosp Gen Univ Elche, Mol Oncol Grp, E-03203 Elche, Spain.
[Perez-Jurado, Luis A.] Hosp Univ Vall Hebron, Programa Med Mol & Genet, E-08035 Barcelona, Spain.
[Perez-Jurado, Luis A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Perez-Jurado, LA (reprint author), Univ Pompeu Fabra, Dept Ciencias Expt Salut, E-08003 Barcelona, Spain.
EM luis.perez@upf.edu
RI Malats, Nuria/H-7041-2015; Valencia, Alfonso/I-3127-2015; Perez Jurado,
Luis Alberto/M-7706-2015; Kogevinas, Manolis/C-3918-2017; Real,
Francisco X/H-5275-2015; Garcia-Closas, Montserrat /F-3871-2015
OI Malats, Nuria/0000-0003-2538-3784; Valencia,
Alfonso/0000-0002-8937-6789; Rodriguez-Santiago,
Benjamin/0000-0003-1167-3852; Real, Francisco X/0000-0001-9501-498X;
Rico, Daniel/0000-0002-6561-2310; Garcia-Closas, Montserrat
/0000-0003-1033-2650
FU NCI Division of Cancer Epidemiology and Genetics; Asociacion Espanola
Contra el Cancer; EU [LSHG-CT-2006-037627,
HEALTH-STREP-2006-037739-DropTop, 201663-UROMOL, 201333-DEC-anBIO];
Fondo de Investigacion Sanitaria [PI076832, PI061614]; Consolider
ONCOBIO; National Institutes of Health [R01 CA089715-06A2]; Red Tematica
de Investigacion Cooperativa en Cancer; Fundacio La Marato de TV3; Fondo
Investigacion Sanitaria [FIS CD06/00019, FI09/00205]
FX We thank D. Pastor, A. Alfaro, M. Marquez, T. Lobato, F. Fernandez, M.
Tora, J. Lloreta, C. Guerrero, C. Ampurdanes, A. Itsara, K. Wang, and M.
Salido for technical assistance, as well as D.G. Pisano, E. Andres, R.
Diaz-Uriarte, G. Gomez, A. Gonzalez-Neira, G. Pita, and I. Cusco for
critical comments. This work was supported by the Intramural Research
Program of the NCI Division of Cancer Epidemiology and Genetics (to
N.R., D.S., and S.J.C.), the Asociacion Espanola Contra el Cancer (to
F.X.R., N.M., and L.A.P.-J.), EU-6FP grants LSHG-CT-2006-037627 (to
L.A.P.-J.) and HEALTH-STREP-2006-037739-DropTop (to N.M. and F.X.R.),
Fondo de Investigacion Sanitaria grants PI076832 (to L.A.P.-J.) and
PI061614 (to F.X.R.), Consolider ONCOBIO (to F.X.R.), National
Institutes of Health grant R01 CA089715-06A2 (to N.M. and F.X.R.), Red
Tematica de Investigacion Cooperativa en Cancer (to N.M. and A.C.),
Fundacio La Marato de TV3 (to N.M.), and EU-7FP grant agreements
#201663-UROMOL (to N.M. and F.X.R.) and #201333-DEC-anBIO (to N.M.).
B.R.-S. and G.M. were supported by a postdoctoral fellowship (FIS
CD06/00019) and a predoctoral fellowship (FI09/00205) of the Fondo
Investigacion Sanitaria, respectively.
NR 39
TC 66
Z9 67
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 9
PY 2010
VL 87
IS 1
BP 129
EP 138
DI 10.1016/j.ajhg.2010.06.002
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 627HD
UT WOS:000280029200014
PM 20598279
ER
PT J
AU Adam, RD
Nigam, A
Seshadri, V
Martens, CA
Farneth, GA
Morrison, HG
Nash, TE
Porcella, SF
Patel, R
AF Adam, Rodney D.
Nigam, Anuranjini
Seshadri, Vishwas
Martens, Craig A.
Farneth, Gregory A.
Morrison, Hilary G.
Nash, Theodore E.
Porcella, Stephen F.
Patel, Rima
TI The Giardia lamblia vsp gene repertoire: characteristics, genomic
organization, and evolution
SO BMC GENOMICS
LA English
DT Article
ID VARIANT SURFACE PROTEIN; CYSTEINE-RICH PROTEIN; ANTIGENIC VARIATION;
EXPRESSION; INTESTINALIS; TROPHOZOITES; PARASITE; REPEATS; FAMILY;
PALMITOYLATION
AB Background: Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP) genes may contribute to this prolonged infection. Only one is expressed at a time, and switching expression from one gene to another occurs by an epigenetic mechanism.
Results: The WB Giardia isolate has been sequenced at 10x coverage and assembled into 306 contigs as large as 870 kb in size. We have used this assembly to evaluate the genomic organization and evolution of the vsp repertoire. We have identified 228 complete and 75 partial vsp gene sequences for an estimated repertoire of 270 to 303, making up about 4% of the genome. The vsp gene diversity includes 30 genes containing tandem repeats, and 14 vsp pairs of identical genes present in either head to head or tail to tail configurations (designated as inverted pairs), where the two genes are separated by 2 to 4 kb of non-coding DNA. Interestingly, over half the total vsp repertoire is present in the form of linear gene arrays that can contain up to 10 vsp gene members. Lastly, evidence for recombination within and across minor clades of vsp genes is provided.
Conclusions: The data we present here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.
C1 [Adam, Rodney D.] Univ Arizona, Dept Med, Coll Med, Tucson, AZ 85721 USA.
[Adam, Rodney D.; Nigam, Anuranjini; Seshadri, Vishwas; Patel, Rima] Univ Arizona, Coll Med, Dept Immunobiol, Tucson, AZ USA.
[Martens, Craig A.; Farneth, Gregory A.; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, RTB,NIH,Rocky Mt Labs, Hamilton, MT USA.
[Morrison, Hilary G.] MBL, Josephine Bay Paul Ctr, Woods Hole, MA USA.
[Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Adam, RD (reprint author), Univ Arizona, Dept Med, Coll Med, Tucson, AZ 85721 USA.
EM adamr@u.arizona.edu
OI Morrison, Hilary/0000-0003-0281-326X
FU NIH/NIAID [AI43273]; NIH, National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX This work was funded in part by NIH/NIAID grant AI43273 and in part by
the Intramural Research Program of the NIH, National Institute of
Allergy and Infectious Diseases, National Institutes of Health. The
funding bodies had no role in data analysis, writing or decision for
submission. We appreciate the work of Anita Mora on the graphics for the
figures.
NR 54
TC 29
Z9 31
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 9
PY 2010
VL 11
AR 424
DI 10.1186/1471-2164-11-424
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 662CZ
UT WOS:000282786000002
PM 20618957
ER
PT J
AU Wang, HB
Chen, RY
Sharp, GB
Brown, K
Smith, K
Ding, GW
Jin, X
Xu, JJ
Dong, RL
Wang, N
AF Wang, Haibo
Chen, Ray Y.
Sharp, Gerald B.
Brown, Katherine
Smith, Kumi
Ding, Guowei
Jin, Xia
Xu, Junjie
Dong, Ruiling
Wang, Ning
TI Mobility, risk behavior and HIV/STI rates among female sex workers in
Kaiyuan City, Yunnan Province, China
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID SEXUALLY-TRANSMITTED-DISEASES; HIV TRANSMISSION; SOUTH-AFRICA;
INFECTION; PREVALENCE; CAMBODIA; INTERVENTION; ACQUISITION; INCREASES;
HIV/AIDS
AB Background: The mobility of female sex workers (FSWs) is a factor in the geographic spread of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study describes FSW mobility patterns in a high risk area of China to identify factors associated with increased mobility, and to study the incidence and prevalence of HIV/STIs in this group.
Methods: 270 FSWs recruited from a baseline cross-sectional study were invited to participate in a one-year monthly follow-up cohort study in Kaiyuan City, Yunnan Province, China from 2006 to 2007. Laboratory tests were conducted for HIV/STIs at baseline, 6 and 12 months.
Results: A total of 117 (43.3%) FSWs moved to another city during the year. Risk factors for increased mobility included being from another city within Yunnan (adjusted hazard ratio [AHR] 1.67, 95% confidence interval [CI] 1.09-2.56), being from outside Yunnan (AHR 1.58, 95% CI 1.04-2.54), and working in lower risk entertainment establishments (AHR 1.55, 95% CI 1.03-2.35). HIV-positive subjects, drug users and FSWs in higher risk venue were less likely to change residence, less likely to use condoms with clients, and earned less per client, but had more working locations and more clients each month.
Conclusions: The least mobile FSWs were from Kaiyuan, worked in higher risk venues, were more likely to use drugs and be HIV-infected. Because FSWs characteristics differ according to the venue at which they work, future prevention work should tailor programs according to venue with a particular focus on FSWs in higher risk venues.
C1 [Brown, Katherine; Smith, Kumi; Ding, Guowei; Jin, Xia; Wang, Ning] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, Beijing 100050, Peoples R China.
[Chen, Ray Y.; Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Xu, Junjie] China Med Univ, Affiliated Hosp 1, Minist Hlth, Key Lab Immunol AIDS, Shenyang 110001, Peoples R China.
[Dong, Ruiling] Shenzhen Port Hosp, Shenzhen Int Travel Hlth Care Ctr, Shenzhen 518033, Peoples R China.
RP Wang, N (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, 27 Nanwei Rd, Beijing 100050, Peoples R China.
EM wangnbj@163.com
OI Chen, Ray/0000-0001-6344-1442
FU National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of Health [U19 AI51915-05]
FX This study was supported by the Comprehensive International Program of
Research on AIDS (CIPRA) grant from the National Institute of Allergy
and Infectious Diseases, U.S. National Institutes of Health (U19
AI51915-05).
NR 29
TC 17
Z9 20
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD JUL 9
PY 2010
VL 10
AR 198
DI 10.1186/1471-2334-10-198
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 666RN
UT WOS:000283136300001
PM 20615260
ER
PT J
AU Rovsing, L
Rath, MF
Lund-Andersen, C
Klein, DC
Moller, M
AF Rovsing, Louise
Rath, Martin F.
Lund-Andersen, Casper
Klein, David C.
Moller, Morten
TI A neuroanatomical and physiological study of the non-image forming
visual system of the cone-rod homeobox gene (Crx) knock out mouse
SO BRAIN RESEARCH
LA English
DT Article
DE Circadian; Melanopsin; Suprachiasmatic; Activity; Temperature
ID RETINAL GANGLION-CELLS; PARAVENTRICULAR NUCLEUS AREA; PINEAL-GLAND;
SUPRACHIASMATIC NUCLEUS; CIRCADIAN PHOTORECEPTION; TEMPERATURE
REGULATION; SPACED DATA; MELANOPSIN; LIGHT; MICE
AB The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-/-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit morphology as in the wild type mouse. In addition, the SCN contain vasoactive intestinal peptide-, vasopressin-, and gastrin-releasing peptide-immunoreactive neurons as present in the wild type. Anterograde in vivo tracings from the retina of the Crx(-/-) and wild type mouse showed that the retinohypothalamic projection to the SCN and the central optic pathways were similar in both animals. Telemetric monitoring of the running activity and temperature revealed that both the Crx(-/-) and wild type mouse exhibited diurnal rhythms with a 24-h period, which could be phase changed by light. However, power spectral analysis revealed that both rhythms in the Crx(-/-) mouse were less robust than those in the wild type. The normal development of the SCN and the central visual pathways in the Crx(-/-) mouse suggests that a modulatory input from the photoreceptors in the peripheral retina to the retinal melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/)- mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse. (C) 2010 Published by Elsevier B.V.
C1 [Rovsing, Louise; Rath, Martin F.; Lund-Andersen, Casper; Moller, Morten] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark.
[Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Moller, M (reprint author), Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, Room 24-3-43,Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
EM morm@sund.ku.dk
RI Rovsing, Louise/E-3225-2014;
OI Rath, Martin/0000-0002-4047-6324
FU Lundbeck Foundation; Danish Medical Research Council [271-07-0412]; Novo
Nordisk Foundation; Carlsberg Foundation; Fonden til Laegevidenskabens
Fremme; Simon Fougner Hartmanns Familiefond; Danish Eye Health Society
(Vaem om Synet); Division of Intramural Research of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
FX This study was supported by the Lundbeck Foundation, the Danish Medical
Research Council (grant number 271-07-0412), the Novo Nordisk
Foundation, the Carlsberg Foundation, Fonden til Laegevidenskabens
Fremme, Simon Fougner Hartmanns Familiefond, the Danish Eye Health
Society (Vaem om Synet), and the Division of Intramural Research of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. The authors wish to express their appreciation to Dr.
Connie Cepko for providing the Crx-/- mice.
NR 53
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUL 9
PY 2010
VL 1343
BP 54
EP 65
DI 10.1016/j.brainres.2010.04.066
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 624GU
UT WOS:000279806000007
PM 20438719
ER
PT J
AU Lorsch, JR
Dever, TE
AF Lorsch, Jon R.
Dever, Thomas E.
TI Molecular View of 43 S Complex Formation and Start Site Selection in
Eukaryotic Translation Initiation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID 40S RIBOSOMAL-SUBUNIT; GTP EXCHANGE FACTORS; TRANSFER-RNA; CODON
SELECTION; CRYSTAL-STRUCTURE; BETA-SUBUNIT; IN-VIVO;
SACCHAROMYCES-CEREVISIAE; CONFORMATIONAL-CHANGE; ELONGATION-FACTORS
AB A central step to high fidelity protein synthesis is selection of the proper start codon. Recent structural, biochemical, and genetic analyses have provided molecular insights into the coordinated activities of the initiation factors in start codon selection. A molecular model is emerging in which start codon recognition is linked to dynamic reorganization of factors on the ribosome and structural changes in the ribosome itself.
C1 [Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Dever, Thomas E.] Eunice Kennedy Shriver NICHD, 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; tdever@nih.gov
OI Dever, Thomas/0000-0001-7120-9678; Lorsch, Jon/0000-0002-4521-4999
FU National Institutes of Health [GM62128]; NICHD, National Institutes of
Health; Human Frontier Science Program
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM62128 (to J.R.L.) and by the Intramural Research Program
of the NICHD, National Institutes of Health (to T. E. D.). This work was
also supported by a grant from the Human Frontier Science Program (to
J.R.L.). This is the third article in the Thematic Minireview Series on
Protein Synthesis. This minireview will be reprinted in the 2010
Minireview Compendium, which will be available in January, 2011.
NR 49
TC 46
Z9 47
U1 0
U2 6
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 JUL 9
PY 2010
VL 285
IS 28
BP 21203
EP 21207
DI 10.1074/jbc.R110.119743
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 620RD
UT WOS:000279516100003
PM 20444698
ER
PT J
AU Lee, S
Miller, M
Shuman, JD
Johnson, PF
AF Lee, Sook
Miller, Maria
Shuman, Jon D.
Johnson, Peter F.
TI CCAAT/Enhancer-binding Protein beta DNA Binding Is Auto-inhibited by
Multiple Elements That Also Mediate Association with p300/CREB-binding
Protein (CBP)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HYDROPHOBIC CLUSTER-ANALYSIS; C/EBP-BETA; TRANSCRIPTION FACTOR;
STRUCTURAL BASIS; LEUCINE-ZIPPER; NF-M; MYELOMONOCYTIC CELLS; CELLULAR
SENESCENCE; V-MYB; PHOSPHORYLATION
AB Signaling through Ras GTPases controls the activity of many transcription factors including CCAAT/enhancer-binding protein (C/EBP beta), which regulates oncogenic H-Ras(V12)-induced senescence and growth arrest. Here we report that C/EBP beta (LAP) DNA binding is inhibited by N-terminal sequences and derepressed by oncogenic Ras signaling. Sequence and mutational analyses showed that auto-repression involves two LXXLF (phi XX phi phi)-like motifs (LX1 and LX2) and a third element, auto-inhibitory domain (AID), located within conserved region CR5. LX1 is a critical component of the transactivation domain and has been shown to mediate C/EBP beta binding to the TAZ2 region of p300/CREB-binding protein coactivators. C/EBP beta auto-repression also involves a C-terminal regulatory domain (CRD) adjacent to the leucine zipper. CRD contains a third phi XX phi phi motif (LX3) and a short sequence, KQL, which has similarity to a region in the protein-binding site of TAZ2. The C/EBP beta N- and C-terminal domains physically associate in a manner that requires the basic region and CRD. We propose a model in which the regulatory sequences form a hydrophobic core that reciprocally inhibits DNA binding and transactivation. We also suggest a mechanism for C/EBP beta derepression involving several recently identified modifications within AID and CRD. Finally, we show that association of activatedC/EBP beta with p300/CREB-binding protein requires the LX2 and AID auto-inhibitory elements. Thus, the N-terminal regulatory elements have dual roles in auto-inhibition and coactivator binding.
C1 [Lee, Sook; Shuman, Jon D.; Johnson, Peter F.] NCI Frederick, Lab Canc Prevent, NIH, Frederick, MD 21702 USA.
[Miller, Maria] NCI Frederick, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
RP Johnson, PF (reprint author), NCI Frederick, Lab Canc Prevent, NIH, Bldg 539,Rm 122, Frederick, MD 21702 USA.
EM johnsope@mail.nih.gov
RI Johnson, Peter/A-1940-2012; Miller, Maria/I-1636-2013;
OI Johnson, Peter/0000-0002-4145-4725; Miller, Maria/0000-0003-0252-5348;
Shuman, Jon/0000-0001-8412-9087
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 55
TC 19
Z9 19
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 JUL 9
PY 2010
VL 285
IS 28
BP 21399
EP 21410
DI 10.1074/jbc.M110.128413
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 620RD
UT WOS:000279516100026
PM 20452968
ER
PT J
AU Li, M
Chen, CA
Davies, DR
Chiu, TK
AF Li, Min
Chen, Changqing
Davies, David R.
Chiu, Thang K.
TI Induced-fit Mechanism for Prolyl Endopeptidase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DIPEPTIDYL-PEPTIDASE-IV; FIBROBLAST ACTIVATION PROTEIN; POSTPROLINE
CLEAVING ENZYME; CRYSTAL-STRUCTURE; SUBSTRATE-SPECIFICITY;
PORPHYROMONAS-GINGIVALIS; SERRATIA-MARCESCENS; GLYCEMIC CONTROL;
STRUCTURAL BASIS; RAT-BRAIN
AB Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the beta-propeller and alpha/beta-hydrolase domains; addition of substrate to preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases.
C1 [Chiu, Thang K.] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA.
[Li, Min; Davies, David R.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Changqing] Chinese Acad Sci, Shanghai Res Ctr Biotechnol, Shanghai 200233, Peoples R China.
RP Chiu, TK (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, 1901 Perdido St, New Orleans, LA 70112 USA.
EM tchiu@lsuhsc.edu
FU United States Department of Energy, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX The use of the Advanced Photon Source was supported by United States
Department of Energy, Office of Basic Energy Sciences, Contract
W-31-109-Eng-38.
NR 67
TC 33
Z9 33
U1 1
U2 13
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 JUL 9
PY 2010
VL 285
IS 28
BP 21487
EP 21495
DI 10.1074/jbc.M109.092692
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 620RD
UT WOS:000279516100035
PM 20444688
ER
PT J
AU Fer, ND
Shoemaker, RH
Monks, A
AF Fer, Nicole D.
Shoemaker, Robert H.
Monks, Anne
TI Adaphostin toxicity in a sensitive non-small cell lung cancer model is
mediated through Nrf2 signaling and heme oxygenase 1
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
ID ANTIOXIDANT-RESPONSIVE ELEMENT; HUMAN NEUROBLASTOMA-CELLS; HUMAN
LEUKEMIA-CELLS; OXIDATIVE STRESS; PHOSPHATIDYLINOSITOL 3-KINASE;
IN-VITRO; INDUCTION; APOPTOSIS; KINASE; ACTIVATION
AB Background: Preclinical toxicity of adaphostin has been related to oxidative stress. This study investigated the regulatory mechanism underlying adaphostin induction of heme oxygenase 1 (HMOX1) which plays a significant role in modulation of drug-induced toxicity in the non-small cell lung cancer cell line model, NCI-H522.
Methods: The transcriptional response of NCI-H522 to adaphostin prominently involved oxidative stress genes, particularly HMOX1. Reactive oxygen species (ROS) involvement was additionally established by generation of ROS prior to modulation of adaphostin-toxicity with antioxidants. To identify up-stream regulatory elements of HMOX1, immunofluorescence was used to evaluate nuclear translocation of the transcription factor, NF-E2-related factor 2 (Nrf2), in the presence of adaphostin. The PI3-kinase inhibitor, wortmannin, was employed as a pharmacological inhibitor of this process.
Results: Generation of ROS provided a substantial foundation for the sensitivity of NCI-H522 to adaphostin. However, in contrast to leukemia cell lines, transcriptional response to oxidative stress was associated with induction of HMOX1, which was dependent on nuclear translocation of the transcription factor, Nrf2. Pretreatment of cells with wortmannin inhibited translocation of Nrf2 and induction of HMOX1. Wortmannin pretreatment was also able to diminish adaphostin induction of HMOX1, and as a consequence, enhance the toxicity of adaphostin to NCI-H522.
Conclusions: Adaphostin-induced oxidative stress in NCI-H522 was mediated through nuclear translocation of Nrf2 leading to upregulation of HMOX1. Inhibition of Nrf2 translocation by wortmannin inhibited this cytoprotective response, and enhanced the toxicity of adaphostin, suggesting that inhibitors of the PI3K pathway, such as wortmannin, might augment the antiproliferative effects of adaphostin in solid tumors that depend on the Nrf2/ARE pathway for protection against oxidative stress.
C1 [Fer, Nicole D.; Monks, Anne] NCI Frederick, Lab Funct Genom, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Shoemaker, Robert H.] NCI Frederick, Sreening Technol Branch, Frederick, MD 21702 USA.
RP Monks, A (reprint author), NCI Frederick, Lab Funct Genom, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA.
EM monksa@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract 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.;
This research was supported by the Developmental Therapeutics Program in
the Division of Cancer Treatment and Diagnosis of the National Cancer
Institute.
NR 30
TC 8
Z9 8
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-9966
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD JUL 9
PY 2010
VL 29
AR 91
DI 10.1186/1756-9966-29-91
PG 7
WC Oncology
SC Oncology
GA 656NK
UT WOS:000282343300001
PM 20618971
ER
PT J
AU Smogorzewska, A
Desetty, R
Saito, TT
Schlabach, M
Lach, FP
Sowa, ME
Clark, AB
Kunkel, TA
Harper, JW
Colaiacovo, MP
Elledge, SJ
AF Smogorzewska, Agata
Desetty, Rohini
Saito, Takamune T.
Schlabach, Michael
Lach, Francis P.
Sowa, Mathew E.
Clark, Alan B.
Kunkel, Thomas A.
Harper, J. Wade
Colaiacovo, Monica P.
Elledge, Stephen J.
TI A Genetic Screen Identifies FAN1, a Fanconi Anemia-Associated Nuclease
Necessary for DNA Interstrand Crosslink Repair
SO MOLECULAR CELL
LA English
DT Article
ID HOLLIDAY JUNCTION RESOLVASES; CANCER SUSCEPTIBILITY GENE; FANCD2
MONOUBIQUITINATION; CAENORHABDITIS-ELEGANS; DAMAGE RESPONSE; STRAND
BREAKS; RECOMBINATION; PATHWAY; PROTEIN; PHOSPHORYLATION
AB The Fanconi anemia (FA) pathway is responsible for interstrand crosslink repair. At the heart of this pathway is the FANCI-FAND2 (ID) complex, which, upon ubiquitination by the FA core complex, travels to sites of damage to coordinate repair that includes nucleolytic modification of the DNA surrounding the lesion and translesion synthesis. How the ID complex regulates these events is unknown. Here we describe a shRNA screen that led to the identification of two nucleases necessary for crosslink repair, FAN1 (KIAA1018) and EXDL2. FAN1 colocalizes at sites of DNA damage with the ID complex in a manner dependent on FAN1's ubiquitin-binding domain (UBZ), the ID complex, and monoubiquitination of FANCD2. FAN1 possesses intrinsic 5'-3' exonuclease activity and endonuclease activity that cleaves nicked and branched structures. We propose that FAN1 is a repair nuclease that is recruited to sites of crosslink damage in part through binding the ubiquitinated ID complex through its UBZ domain.
C1 [Smogorzewska, Agata; Schlabach, Michael; Elledge, Stephen J.] Harvard Univ, Sch Med,Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Genet,Dept Med,Div Genet, Boston, MA 02115 USA.
[Smogorzewska, Agata] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Smogorzewska, Agata; Desetty, Rohini; Lach, Francis P.] Rockefeller Univ, Lab Genome Maintenance, New York, NY 10065 USA.
[Sowa, Mathew E.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Smogorzewska, A (reprint author), Harvard Univ, Sch Med,Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Genet,Dept Med,Div Genet, Boston, MA 02115 USA.
EM asmogorzewska@rockefeller.edu; selledge@genetics.med.harvard.edu
RI Smogorzewska, Agata/B-8891-2011; Saito, Takamune/G-2294-2014
OI Saito, Takamune/0000-0002-4447-4115
FU National Institutes of Health (NIH) [R01GM072551]; CMCR
[1U19A1067751-01]; Giovanni Armenise-Harvard Foundation; Division of
Intramural Research of the National Institute of Environmental Health
Sciences, NIH [Z01 ES065089]; Burroughs Wellcome Fund; [T32CA09216]
FX We thank Jen Svendsen and members of the Elledge lab for protocols and
discussion. Special thanks to Alberto Ciccia for insightful suggestions
and comments. This work is supported by grants from the National
Institutes of Health (NIH) and CMCR grant #1U19A1067751-01 to S.J.E.,
NIH grant R01GM072551 and a Giovanni Armenise-Harvard Foundation award
to M.P.C., a NIH grant to J.W.H., and Project Z01 ES065089 to T.A.K., in
the Division of Intramural Research of the National Institute of
Environmental Health Sciences, NIH. A.S. was supported by T32CA09216 to
the Pathology Department at the Massachusetts General Hospital and by
Burroughs Wellcome Fund Career Award for Medical Scientists and is an
Irma T. Hirschl scholar. S.J.E. is an investigator of the Howard Hughes
Medical Institute.
NR 52
TC 174
Z9 187
U1 0
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 9
PY 2010
VL 39
IS 1
BP 36
EP 47
DI 10.1016/j.molcel.2010.06.023
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 628RT
UT WOS:000280139200006
PM 20603073
ER
PT J
AU Han, YW
Mizuuchi, K
AF Han, Yong-Woon
Mizuuchi, Kiyoshi
TI Phage Mu Transposition Immunity: Protein Pattern Formation along DNA by
a Diffusion-Ratchet Mechanism
SO MOLECULAR CELL
LA English
DT Article
ID TARGET IMMUNITY; STRAND-TRANSFER; B-PROTEIN; BACTERIOPHAGE-MU; COMPLEX;
PLASMID; FLEXIBILITY
AB DNA transposons integrate into host chromosomes with limited target sequence specificity. Without mechanisms to avoid insertion into themselves, transposons risk self-destruction. Phage Mu avoids this problem by transposition immunity, involving MuA-transposase and MuB ATP-dependent DNA-binding protein. MuB-bound DNA acts as an efficient transposition target, but MuA clusters bound to Mu DNA ends activate the MuB-ATPase and dissociate MuB from their neighborhood before target site commitment, making the regions near Mu ends a poor target. This MuA-cluster-MuB interaction requires formation of DNA loops between the MuA- and the MuB-bound DNA sites. At early times, MuB clusters are disassembled via loops with smaller average size, and at later times, MuA clusters find distantly located MuB clusters by forming loops with larger average sizes. We demonstrate that iterative loop formation/disruption cycles with intervening diffusional steps result in larger DNA loops, leading to preferential insertion of the transposon at sites distant from the transposon ends.
C1 [Han, Yong-Woon; Mizuuchi, Kiyoshi] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM kmizu@helix.nih.gov
FU NIDDK; NIH; HHS; US Government
FX We are grateful to Vassili Ivanov for his help with the microscope
system used for this study and to Vassili Ivanov, Eric Greene, Robert
Craigie, and Wei Yang for helpful discussion. This work was supported by
the intramural research fund for NIDDK, NIH, HHS, US Government.
NR 23
TC 17
Z9 17
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 9
PY 2010
VL 39
IS 1
BP 48
EP 58
DI 10.1016/j.molcel.2010.06.013
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 628RT
UT WOS:000280139200007
PM 20603074
ER
PT J
AU Csordas, G
Varnai, P
Golenar, T
Roy, S
Purkins, G
Schneider, TG
Balla, T
Hajnoczky, G
AF Csordas, Gyoergy
Varnai, Peter
Golenar, Tuende
Roy, Swati
Purkins, George
Schneider, Timothy G.
Balla, Tamas
Hajnoczky, Gyorgy
TI Imaging Interorganelle Contacts and Local Calcium Dynamics at the
ER-Mitochondrial Interface
SO MOLECULAR CELL
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; SIGNAL TRANSMISSION; RYANODINE RECEPTORS;
RAT-LIVER; CA2+; DETERMINANTS; MICRODOMAINS; APOPTOSIS; CHANNELS;
BIOLOGY
AB The ER-mitochondrial junction provides a local calcium signaling domain that is critical for both matching energy production with demand and the control of apoptosis. Here, we visualize ER-mitochondrial contact sites and monitor the localized [Ca(2+)] changes ([Ca(2+)](ER-mt)) using drug-inducible fluorescent interorganelle linkers. We show that all mitochondria have contacts with the ER, but plasma membrane (PM)-mitochondrial contacts are less frequent because of interleaving ER stacks in both RBL-2H3 and H9c2 cells. Single mitochondria display discrete patches of ER contacts and show heterogeneity in the ER-mitochondrial Ca(2+) transfer. Pericam-tagged linkers revealed IP(3)-induced ([Ca(2+)](ER-mt)) signals that exceeded 9 mu M and endured buffering bulk cytoplasmic [Ca(2+)] increases. Altering linker length to modify the space available for the Ca(2+) transfer machinery had a biphasic effect on [Ca(2+)](ER-mt) signals. These studies provide direct evidence for the existence of high-Ca(2+) microdomains between the ER and mitochondria and suggest an optimal gap width for efficient Ca2+ transfer.
C1 [Csordas, Gyoergy; Golenar, Tuende; Roy, Swati; Purkins, George; Schneider, Timothy G.; Hajnoczky, Gyorgy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Varnai, Peter] Semmelweis Univ, Dept Physiol, Budapest, Hungary.
[Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Hajnoczky, G (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
EM gyorgy.hajnoczky@jefferson.edu
OI Balla, Tamas/0000-0002-9077-3335
FU Thomas Jefferson Pilot Research Award; NIH [DK051526, RC2AA019416];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health; Hungarian Scientific
Research Fund [OTKA NF-68563]; Medical Research Council of Hungary [ETT
494/2009]
FX The authors thank Sudipto Das for his expert technical help. This work
was supported by a Thomas Jefferson Pilot Research Award to G.C. and by
NIH grants (DK051526 and RC2AA019416) to G.H. The research of T.B. was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development of the
National Institutes of Health. P.V. was supported by grants from the
Hungarian Scientific Research Fund (OTKA NF-68563) and the Medical
Research Council (ETT 494/2009) of Hungary.
NR 39
TC 213
Z9 216
U1 3
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 9
PY 2010
VL 39
IS 1
BP 121
EP 132
DI 10.1016/j.molcel.2010.06.029
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 628RT
UT WOS:000280139200013
PM 20603080
ER
PT J
AU Jugessur, A
Shi, M
Gjessing, HK
Lie, RT
Wilcox, AJ
Weinberg, CR
Christensen, K
Boyles, AL
Daack-Hirsch, S
Nguyen, TT
Christiansen, L
Lidral, AC
Murray, JC
AF Jugessur, Astanand
Shi, Min
Gjessing, Hakon Kristian
Lie, Rolv Terje
Wilcox, Allen James
Weinberg, Clarice Ring
Christensen, Kaare
Boyles, Abee Lowman
Daack-Hirsch, Sandra
Nguyen, Truc Trung
Christiansen, Lene
Lidral, Andrew Carl
Murray, Jeffrey Clark
TI Maternal Genes and Facial Clefts in Offspring: A Comprehensive Search
for Genetic Associations in Two Population-Based Cleft Studies from
Scandinavia
SO PLOS ONE
LA English
DT Article
ID MILLER-DIEKER-SYNDROME; SPONDYLOCARPOTARSAL SYNOSTOSIS SYNDROME;
TUMOR-SUPPRESSOR GENE; CANDIDATE-GENE; ORAL CLEFTS; SKELETAL
DEVELOPMENT; GENOME-SCAN; PALATE; LIP; MICE
AB Background: Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.
Methodology/Principal Findings: Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects [1]. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects. Two complementary statistical methods, TRIMM and HAPLIN, were used to detect multi-marker effects in population-based samples from Norway (562 case-parent and 592 control-parent triads) and Denmark (235 case-parent triads). We analyzed isolated cleft lip with or without cleft palate (iCL/P) and isolated cleft palate only (iCP) separately and assessed replication by looking for genes detected in both populations by both methods. In iCL/P, neither TRIMM nor HAPLIN detected more genes than expected by chance alone; furthermore, the selected genes were not replicated across the two methods. In iCP, however, FLNB was identified by both methods in both populations. Although HIC1 and ZNF189 did not fully satisfy our stringency criterion for replication, they were strongly associated with iCP in TRIMM analyses of the Norwegian triads.
Conclusion/Significance: Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.
C1 [Jugessur, Astanand; Gjessing, Hakon Kristian] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Jugessur, Astanand] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Shi, Min; Weinberg, Clarice Ring] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Gjessing, Hakon Kristian; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Lie, Rolv Terje; Nguyen, Truc Trung] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
[Wilcox, Allen James; Boyles, Abee Lowman] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Christensen, Kaare; Christiansen, Lene; Murray, Jeffrey Clark] Univ So Denmark, Dept Epidemiol, Odense, Denmark.
[Daack-Hirsch, Sandra] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA.
[Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Biol Sci, Iowa City, IA USA.
RP Jugessur, A (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
EM jeff-murray@uiowa.edu
RI Christensen, Kaare/C-2360-2009; Gjessing, Hakon/A-5871-2012;
OI Christensen, Kaare/0000-0002-5429-5292; Boyles,
Abee/0000-0002-8711-2077; Wilcox, Allen/0000-0002-3376-1311
FU National Institutes of Health (NIH) [N01-HG-65403, DE08559, P60 DE13076,
NIH P30 ES05605, RO1 DE-11948-04]; National Institute of Environmental
Health Sciences; Norwegian Research Council [NFR 177522]
FX Center for Inherited Disease Research (CIDR) is fully funded through a
federal contract from the National Institutes of Health (NIH) to The
Johns Hopkins University, Contract Number N01-HG-65403. This research
was supported in part by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences; by NIH grants
DE08559, P60 DE13076, NIH P30 ES05605, and RO1 DE-11948-04; and by the
Norwegian Research Council (NFR 177522). We also thank the US National
Institute of Dental and Craniofacial Research (NIDCR) for underwriting a
significant proportion of the genotyping costs by CIDR. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 47
TC 19
Z9 19
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 9
PY 2010
VL 5
IS 7
AR e11493
DI 10.1371/journal.pone.0011493
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 623CM
UT WOS:000279715300008
PM 20634891
ER
PT J
AU Kuka, M
Baronio, R
Valentini, S
Monaci, E
Muzzi, A
Aprea, S
De Gregorio, E
D'Oro, U
AF Kuka, Mirela
Baronio, Roberta
Valentini, Sara
Monaci, Elisabetta
Muzzi, Alessandro
Aprea, Susanna
De Gregorio, Ennio
D'Oro, Ugo
TI Src Kinases Are Required for a Balanced Production of IL-12/IL-23 in
Human Dendritic Cells Activated by Toll-Like Receptor Agonists
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR-BETA; T-HELPER-CELLS; TYROSINE KINASES; C-REL;
DIFFERENTIATION; INTERLEUKIN-23; PROTEIN; INFLAMMATION; CYTOKINE; TLR
AB Background: Pathogen recognition by dendritic cells (DC) is crucial for the initiation of both innate and adaptive immune responses. Activation of Toll-like Receptors (TLRs) by microbial molecular patterns leads to the maturation of DC, which present the antigen and activate T cells in secondary lymphoid tissues. Cytokine production by DC is critical for shaping the adaptive immune response by regulating T helper cell differentiation. It was previously shown by our group that Src kinases play a key role in cytokines production during TLR4 activation in human DC.
Principal Findings: In this work we investigated the role of Src kinases during different TLRs triggering in human monocyte-derived DC (MoDC). We found that Src family kinases are important for a balanced production of inflammatory cytokines by human MoDC upon stimulation of TLR3 and 8 with their respective agonists. Disruption of this equilibrium through pharmacological inhibition of Src kinases alters the DC maturation pattern. In particular, while expression of IL-12 and other inflammatory cytokines depend on Src kinases, the induction of IL-23 and co-stimulatory molecules do not. Accordingly, DC treated with Src inhibitors are not compromised in their ability to induce CD4 T cell proliferation and to promote the Th17 subset survival but are less efficient in inducing Th1 differentiation.
Conclusions: We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases.
C1 [Kuka, Mirela; Baronio, Roberta; Valentini, Sara; Monaci, Elisabetta; Muzzi, Alessandro; Aprea, Susanna; De Gregorio, Ennio; D'Oro, Ugo] Novartis Vaccines, Siena, Italy.
RP Kuka, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM ugo.doro@novartis.com
RI De Gregorio, Ennio/J-8073-2012;
OI KUKA, MIRELA/0000-0001-9418-1559
FU European Network of Excellence DC-THERA [LSHB-CT-2004-512074]; Novartis
Vaccines and Diagnostics; DC-THERA
FX This work was partially supported by the European Network of Excellence
DC-THERA (contract number LSHB-CT-2004-512074). Mirela Kuka was
supported by a Fellowship from the DC-THERA network. The DC-THERA
Network had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Novartis Vaccines
and Diagnostics partially funded this work, and approved all the
author's decision about study design, data collection and analysis, and
decision to publish.
NR 37
TC 7
Z9 8
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 9
PY 2010
VL 5
IS 7
AR e11491
DI 10.1371/journal.pone.0011491
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 623CM
UT WOS:000279715300006
PM 20634889
ER
PT J
AU Oleksyk, TK
Nelson, GW
An, P
Kopp, JB
Winkler, CA
AF Oleksyk, Taras K.
Nelson, George W.
An, Ping
Kopp, Jeffrey B.
Winkler, Cheryl A.
TI Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles
and Haplotypes: Evidence of Historical Selection in Africa
SO PLOS ONE
LA English
DT Article
ID RECENT POSITIVE SELECTION; NATURAL-SELECTION; HUMAN-POPULATIONS; HUMAN
GENOME; LINKAGE DISEQUILIBRIUM; DIABETES-MELLITUS; GENETICS; AMERICANS;
SOFTWARE; GENOTYPE
AB MYH9 was recently identified as renal susceptibility gene (OR 3-8, p<10(-8)) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (>= 60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12-23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50-80%), less frequent in populations from the Middle East (9-27%) and Europe (0- 9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (F(ST)) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; F(ST) ranged from 0.27-0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (F(ST(CEU vs. YRI)) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (F(ST) = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations.
C1 [Oleksyk, Taras K.] Univ Puerto Rico, Dept Biol, Mayaguez, PR USA.
[Nelson, George W.; An, Ping; Winkler, Cheryl A.] SAIC Frederick, Lab Genom Divers, Frederick, MD USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
RP Oleksyk, TK (reprint author), Univ Puerto Rico, Dept Biol, Mayaguez, PR USA.
EM winklerc@mail.nih.gov
RI Rinaldi2, Carlos/D-4479-2011; Taras, Oleksyk/J-8805-2013;
OI Taras, Oleksyk/0000-0002-8148-3918; Kopp, Jeffrey/0000-0001-9052-186X
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E, RO1 DK 070941, RO1 RFA-CA-09-003]; National
Institute for Diabetes, Digestive, and Kidney Diseases [ZO-1 DK043308]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E, the Intramural Research Programs of the
National Institute for Diabetes, Digestive, and Kidney Diseases (ZO-1
DK043308), and by a grant from the NIH (RO1 DK 070941 (BIF)) and (RO1
RFA-CA-09-003 (CAW)). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 20
Z9 21
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 9
PY 2010
VL 5
IS 7
AR e11474
DI 10.1371/journal.pone.0011474
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 623CM
UT WOS:000279715300002
PM 20634883
ER
PT J
AU Volkow, ND
Wang, GJ
Tomasi, D
Telang, F
Fowler, JS
Pradhan, K
Jayne, M
Logan, J
Goldstein, RZ
Alia-Klein, N
Wong, C
AF Volkow, Nora D.
Wang, Gene-Jack
Tomasi, Dardo
Telang, Frank
Fowler, Joanna S.
Pradhan, Kith
Jayne, Millard
Logan, Jean
Goldstein, Rita Z.
Alia-Klein, Nelly
Wong, Christopher
TI Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues
Exposure in Cocaine Abusers
SO PLOS ONE
LA English
DT Article
ID DOPAMINE SYSTEM REGULATION; NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR;
EXTRACELLULAR DOPAMINE; INTRAVENOUS COCAINE; GLUCOSE-UTILIZATION;
ADDICTION; DEPENDENCE; STRIATUM; RATS
AB Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and (18)FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
[Volkow, Nora D.; Tomasi, Dardo; Telang, Frank; Jayne, Millard] NIAAA, Lab Neuroimaging, Bethesda, MD USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Pradhan, Kith; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015;
OI Logan, Jean/0000-0002-6993-9994
FU National Institutes of Health; Department of Energy (DOE)
[DE-AC01-76CH00016]
FX Research was supported by the National Institutes of Health Intramural
Research Program (NIAAA) and by the Department of Energy (DOE)
(DE-AC01-76CH00016). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 32
Z9 33
U1 1
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 JUL 9
PY 2010
VL 5
IS 7
AR e11509
DI 10.1371/journal.pone.0011509
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 623CM
UT WOS:000279715300020
PM 20634975
ER
PT J
AU Zhang, XW
Bearer, EL
Boulat, B
Hall, FS
Uhl, GR
Jacobs, RE
AF Zhang, Xiaowei
Bearer, Elaine L.
Boulat, Benoit
Hall, F. Scott
Uhl, George R.
Jacobs, Russell E.
TI Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain
SO PLOS ONE
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; DEFORMATION-BASED MORPHOMETRY; PREPULSE
INHIBITION DEFICITS; VIVO H-1-NMR SPECTROSCOPY; MEDIAL PREFRONTAL
CORTEX; TENSOR-BASED MORPHOMETRY; VENTRAL TEGMENTAL AREA; IN-VIVO;
SEROTONIN-TRANSPORTER; ALZHEIMERS-DISEASE
AB The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here.
C1 [Zhang, Xiaowei; Bearer, Elaine L.; Boulat, Benoit; Jacobs, Russell E.] CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 USA.
[Bearer, Elaine L.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Hall, F. Scott; Uhl, George R.] Natl Inst Drug Abuse, Intramural Res Program, Mol Neurobiol Branch, Baltimore, MD USA.
RP Zhang, XW (reprint author), CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 USA.
EM rjacobs@caltech.edu
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU Beckman Institute; NINDS [RO1 NS062184, RO1 NS046810]; NIDA
[R01DA18184]; NCRR [U24 RR021760]; National Institute on Drug Abuse,
Intramural Research Program
FX The project was funded in part by the Beckman Institute, NINDS RO1
NS062184 and RO1 NS046810 (E.L.B.), NIDA R01DA18184, and NCRR U24
RR021760 Mouse BIRN (R.E.J.) and, in part, by the National Institute on
Drug Abuse, Intramural Research Program (G.R.U. and F.S.H.). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 129
TC 30
Z9 31
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 9
PY 2010
VL 5
IS 7
AR e11506
DI 10.1371/journal.pone.0011506
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 623CM
UT WOS:000279715300017
PM 20634895
ER
PT J
AU Trono, D
Van Lint, C
Rouzioux, C
Verdin, E
Barre-Sinoussi, F
Chun, TW
Chomont, N
AF Trono, Didier
Van Lint, Carine
Rouzioux, Christine
Verdin, Eric
Barre-Sinoussi, Francoise
Chun, Tae-Wook
Chomont, Nicolas
TI HIV Persistence and the Prospect of Long-Term Drug-Free Remissions for
HIV-Infected Individuals
SO SCIENCE
LA English
DT Review
ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; RALTEGRAVIR
INTENSIFICATION; DISEASE PROGRESSION; CELLULAR RESERVOIRS; ANTIVIRAL
THERAPY; EXTENDED PERIODS; LATENT RESERVOIR; VIRUS-INFECTIONS; VALPROIC
ACID
AB HIV infection can persist in spite of efficacious antiretroviral therapies. Although incomplete inhibition of viral replication may contribute to this phenomenon, this is largely due to the early establishment of a stable reservoir of latently infected cells. Thus, life-long antiviral therapy may be needed to control HIV. Such therapy is prone to drug resistance and cumulative side effects and is an unbearable financial burden for regions of the world hit hardest by the epidemic. This review discusses our current understanding of HIV persistence and the limitations of potential approaches to eradicate the virus and accordingly pleads for a joint multidisciplinary effort toward two highly related goals: the development of an HIV prophylactic vaccine and the achievement of long-term drug-free remissions in HIV-infected individuals.
C1 [Trono, Didier] Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland.
[Trono, Didier] Ecole Polytech Fed Lausanne, Frontiers in Genet Program, CH-1015 Lausanne, Switzerland.
[Van Lint, Carine] Univ Libre Bruxelles, IBMM, B-6041 Gosselies, Belgium.
[Rouzioux, Christine] Univ Paris 05, CHU Necker, F-75743 Paris, France.
[Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Barre-Sinoussi, Francoise] Inst Pasteur, Dept Virol, Unit Regulat Retroviral Infect, F-75015 Paris, France.
[Chun, Tae-Wook] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chomont, Nicolas] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
RP Trono, D (reprint author), Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland.
EM Didier.trono@epfl.ch
RI Barre-Sinoussi, Francoise/G-8355-2011;
OI Verdin, Eric/0000-0003-3703-3183
FU Swiss National Science Foundation; National Institutes of Health;
Belgian National Fund for Scientific Research; Programme of Excellence
"Cibles" of the Walloon Region; Agence Nationale de Recherche sur le
Syndrome d'Immuno-Deficience Acquis (SIDA); SIDACTION (Ensemble Contre
le SIDA); AMfAR (the Foundation for AIDS Research)
FX We thank Marie-Capucine Penicaud, from the International AIDS Society,
for coordinating the launching of this review, and the Swiss National
Science Foundation, the National Institutes of Health, the Belgian
National Fund for Scientific Research, the Programme of Excellence
"Cibles" of the Walloon Region, the Agence Nationale de Recherche sur le
Syndrome d'Immuno-Deficience Acquis (SIDA), SIDACTION (Ensemble Contre
le SIDA), AMfAR (the Foundation for AIDS Research), and other agencies
and foundations supporting work in our laboratories.
NR 74
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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 JUL 9
PY 2010
VL 329
IS 5988
BP 174
EP 180
DI 10.1126/science.1191047
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 622CB
UT WOS:000279635200037
PM 20616270
ER
PT J
AU Gahlay, G
Gauthier, L
Baibakov, B
Epifano, O
Dean, J
AF Gahlay, Gagandeep
Gauthier, Lyn
Baibakov, Boris
Epifano, Olga
Dean, Jurrien
TI Gamete Recognition in Mice Depends on the Cleavage Status of an Egg's
Zona Pellucida Protein
SO SCIENCE
LA English
DT Article
ID SPERM RECEPTOR ACTIVITY; MOUSE SPERM; FERTILIZATION; ZP3; BINDING;
INACTIVATION; FERTILITY; GLYCANS; GENE
AB At fertilization, mouse sperm bind to the zona pellucida (which consists of glycoproteins ZP1, ZP2, and ZP3) that surrounds eggs. A ZP2 cleavage model of gamete recognition requires intact ZP2, and a glycan release model postulates that zona glycans are ligands for sperm. These two models were tested by replacing endogenous protein with ZP2 that cannot be cleaved (Zp2(Mut)) or with ZP3 lacking implicated O glycans (Zp3(Mut)). Sperm bound to two-cell Zp2(Mut) embryos despite fertilization and cortical granule exocytosis. Contrary to prediction, sperm fertilized Zp3(Mut) eggs. Sperm at the surface of the zona pellucida remained acrosome-intact for more than 2 hours and were displaced by additional sperm. These data indicate that sperm-egg recognition depends on the cleavage status of ZP2 and that binding at the surface of the zona is not sufficient to induce sperm acrosome exocytosis.
C1 [Gahlay, Gagandeep; Gauthier, Lyn; Baibakov, Boris; Epifano, Olga; Dean, Jurrien] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Dean, J (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jurrien@helix.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of NIH,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 18
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U1 0
U2 10
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 JUL 9
PY 2010
VL 329
IS 5988
BP 216
EP 219
DI 10.1126/science.1188178
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 622CB
UT WOS:000279635200049
PM 20616279
ER
PT J
AU Vicente, DA
Henry, LR
Hahm, G
Soballe, PW
Smart, D
AF Vicente, Diego A.
Henry, Leonard R.
Hahm, George
Soballe, Peter W.
Smart, DeeDee
TI Axillary sentinel lymph node biopsy after mastectomy: a case report
SO WORLD JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
ID RECURRENT BREAST-CANCER; CARCINOMA; SURGERY
AB Background: Sentinel lymph node biopsy has been established as the preferred method for staging early breast cancer. A prior history of mastectomy is felt to be a contraindication.
Case presentation: A patient with recurrent breast cancer in her skin flap was discovered to have positive axillary sentinel nodes by sentinel lymph node biopsy five years after mastectomy for ductal carcinoma in situ.
Conclusion: A prior history of mastectomy may not be an absolute contraindication to sentinel lymph node biopsy.
C1 [Vicente, Diego A.; Henry, Leonard R.; Hahm, George] Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA.
[Henry, Leonard R.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Soballe, Peter W.] USN, San Diego Med Ctr, Dept Surg, San Diego, CA 92152 USA.
[Smart, DeeDee] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Vicente, DA (reprint author), Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA.
EM diegoavicente@gmail.com
NR 25
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U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7819
J9 WORLD J SURG ONCOL
JI World J. Surg. Oncol.
PD JUL 9
PY 2010
VL 8
AR 59
DI 10.1186/1477-7819-8-59
PG 3
WC Oncology; Surgery
SC Oncology; Surgery
GA 630XT
UT WOS:000280309700001
PM 20618969
ER
PT J
AU Kato, GJ
Sachdev, V
AF Kato, Gregory J.
Sachdev, Vandana
TI Diastolic dysfunction in sickle cell
SO BLOOD
LA English
DT Editorial Material
ID OBSTRUCTIVE SLEEP-APNEA; RISK-FACTOR; DISEASE; DEATH; DESATURATION;
HYPERTENSION; CHILDREN; ANEMIA
C1 [Kato, Gregory J.; Sachdev, Vandana] NIH, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NIH, Bethesda, MD 20892 USA.
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006012-01, ZIA HL006012-02, ZIA HL006014-01,
ZIA HL006014-02]
NR 10
TC 1
Z9 1
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 JUL 8
PY 2010
VL 116
IS 1
BP 1
EP 2
DI 10.1182/blood-2010-04-279919
PG 2
WC Hematology
SC Hematology
GA 622DX
UT WOS:000279641400001
PM 20616222
ER
PT J
AU Bullock, GC
Delehanty, LL
Talbot, AL
Gonias, SL
Tong, WH
Rouault, TA
Dewar, B
Macdonald, JM
Chruma, JJ
Goldfarb, AN
AF Bullock, Grant C.
Delehanty, Lorrie L.
Talbot, Anne-Laure
Gonias, Sara L.
Tong, Wing-Hang
Rouault, Tracey A.
Dewar, Brian
Macdonald, Jeffrey M.
Chruma, Jason J.
Goldfarb, Adam N.
TI Iron control of erythroid development by a novel aconitase-associated
regulatory pathway
SO BLOOD
LA English
DT Article
ID MITOCHONDRIAL ACONITASE; DEFICIENCY ANEMIA; CHRONIC DISEASE; RAT-LIVER;
PROTEIN; ERYTHROPOIESIS; IDENTIFICATION; TRANSFERRIN; HOMEOSTASIS;
INHIBITION
AB Human red cell differentiation requires the action of erythropoietin on committed progenitor cells. In iron deficiency, committed erythroid progenitors lose responsiveness to erythropoietin, resulting in hypoplastic anemia. To address the basis for iron regulation of erythropoiesis, we established primary hematopoietic cultures with transferrin saturation levels that restricted erythropoiesis but permitted granulopoiesis and megakaryopoiesis. Experiments in this system identified as a critical regulatory element the aconitases, multifunctional iron-sulfur cluster proteins that metabolize citrate to isocitrate. Iron restriction suppressed mitochondrial and cytosolic aconitase activity in erythroid but not granulocytic or megakaryocytic progenitors. An active site aconitase inhibitor, fluorocitrate, blocked erythroid differentiation in a manner similar to iron deprivation. Exogenous isocitrate abrogated the erythroid iron restriction response in vitro and reversed anemia progression in iron-deprived mice. The mechanism for aconitase regulation of erythropoiesis most probably involves both production of metabolic intermediates and modulation of erythropoietin signaling. One relevant signaling pathway appeared to involve protein kinase C alpha/beta, or possibly protein kinase C delta, whose activities were regulated by iron, isocitrate, and erythropoietin. (Blood. 2010; 116(1): 97-108)
C1 [Bullock, Grant C.; Delehanty, Lorrie L.; Talbot, Anne-Laure; Gonias, Sara L.; Goldfarb, Adam N.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA.
[Tong, Wing-Hang; Rouault, Tracey A.] NICHHD, Program Mol Med, Bethesda, MD 20892 USA.
[Dewar, Brian; Macdonald, Jeffrey M.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA.
[Chruma, Jason J.] Univ Virginia, Dept Chem, Charlottesville, VA USA.
RP Goldfarb, AN (reprint author), Univ Virginia, Sch Med, Dept Pathol, POB 800904, Charlottesville, VA 22908 USA.
EM ang3x@virginia.edu
FU Ruth L. Kirschstein National Research Service; National Institutes of
Health [F32 HL0860046]; University of Virginia; University of Virginia
Cancer Center; NCI Cancer Center [P30 CA44579]; Ivy Foundation; National
Institute of Diabetes and Digestive and Kidney Diseases [R01 DK079924];
Roche Foundation for Anemia Research
FX This work was supported by a Ruth L. Kirschstein National Research
Service Award, by the National Institutes of Health (grant F32
HL0860046), and by a University of Virginia K12 Clinical Translational
Career Development Award (G. C. B.); by the University of Virginia
Cancer Center through the James and Rebecca Craig Cancer Research
Scholars Award and the NCI Cancer Center Support (grant P30 CA44579), by
the Biomedical Innovation Fund of the Ivy Foundation (J.J.C.); by the
National Institute of Diabetes and Digestive and Kidney Diseases (grant
R01 DK079924; A.N.G.); and by the Roche Foundation for Anemia Research.
NR 50
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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 JUL 8
PY 2010
VL 116
IS 1
BP 97
EP 108
DI 10.1182/blood-2009-10-251496
PG 12
WC Hematology
SC Hematology
GA 622DX
UT WOS:000279641400016
PM 20407036
ER
PT J
AU Sundaram, N
Tailor, A
Mendelsohn, L
Wansapura, J
Wang, XD
Higashimoto, T
Pauciulo, MW
Gottliebson, W
Kalra, VK
Nichols, WC
Kato, GJ
Malik, P
AF Sundaram, Nambirajan
Tailor, Anitaben
Mendelsohn, Laurel
Wansapura, Janaka
Wang, Xunde
Higashimoto, Tomoyasu
Pauciulo, Michael W.
Gottliebson, William
Kalra, Vijay K.
Nichols, William C.
Kato, Gregory J.
Malik, Punam
TI High levels of placenta growth factor in sickle cell disease promote
pulmonary hypertension
SO BLOOD
LA English
DT Article
ID MOUSE MODEL; HEMOLYSIS; ASSOCIATION; EXPRESSION; RECEPTOR; ENDOTHELIN-1;
INFLAMMATION; HEMOGLOBIN; ACTIVATION; MORTALITY
AB Pulmonary hypertension is associated with reduced nitric oxide bioavailability and early mortality in sickle cell disease (SCD). We previously demonstrated that placenta growth factor (PlGF), an angiogenic factor produced by erythroid cells, induces hypoxia-independent expression of the pulmonary vasoconstrictor endothelin-1 in pulmonary endothelial cells. Using a lentivirus vector, we simulated erythroid expression of PlGF in normal mice up to the levels seen in sickle mice. Consequently, endothelin-1 production increased, right ventricle pressures increased, and right ventricle hypertrophy and pulmonary changes occurred in the mice within 8 weeks. These findings were corroborated in 123 patients with SCD, in whom plasma PlGF levels were significantly associated with anemia, endothelin-1, and tricuspid regurgitant velocity; the latter is reflective of peak pulmonary artery pressure. These results illuminate a novel mechanistic pathway linking hemolysis and erythroid hyperplasia to increased PlGF, endothelin-1, and pulmonary hypertension in SCD, and suggest that strategies that block PlGF signaling may be therapeutically beneficial. This trial was registered at http://clinicaltrials.gov as #NCT00011648. (Blood. 2010; 116(1): 109-112)
C1 [Tailor, Anitaben; Mendelsohn, Laurel; Wang, Xunde; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Sundaram, Nambirajan; Higashimoto, Tomoyasu; Malik, Punam] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Wansapura, Janaka] Cincinnati Childrens Hosp Med Ctr, Div Radiol, Cincinnati, OH 45229 USA.
[Pauciulo, Michael W.; Nichols, William C.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.
[Gottliebson, William] Cincinnati Childrens Hosp Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA.
[Kalra, Vijay K.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[Malik, Punam] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Inst, Div Hematol Oncol, Cincinnati, OH 45229 USA.
RP Kato, GJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10CRC,Rm 5-5140, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov; Punam.Malik@cchmc.org
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[1RO1 70135, U54 HL-06-008]; Division of Intramural Research, National
Heart, Lung, and Blood Institute
FX This work was supported in part by National Institutes of
Health/National Heart, Lung, and Blood Institute (1RO1 70135 and U54
HL-06-008; P. M). A. T., L. M., X. W., and G.J.K. were supported by the
Division of Intramural Research, National Heart, Lung, and Blood
Institute.
NR 27
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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 JUL 8
PY 2010
VL 116
IS 1
BP 109
EP 112
DI 10.1182/blood-2009-09-244830
PG 4
WC Hematology
SC Hematology
GA 622DX
UT WOS:000279641400017
PM 20335221
ER
PT J
AU Shanker, A
AF Shanker, Anil
TI Adaptive control of innate immunity
SO IMMUNOLOGY LETTERS
LA English
DT Review
DE Adaptive immunity; Innate immunity; T cells; NK cells; Inflammation;
Activation; Effector response
ID REGULATORY T-CELLS; NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR;
IFN-GAMMA; PROTECTIVE IMMUNITY; CEREBROSPINAL-FLUID; ADIPOSE-TISSUE;
LYMPH-NODES; RESPONSES; ACTIVATION
AB The mechanisms by which the immune system responds to an infection or disease depend on a complex interplay between the elements of innate and adaptive immunity. While most of the focus so far has been on the innate instruction of the adaptive immune responses, considerable evidence now suggests an equally important adaptive control of the innate immunity. Several studies yield new insights into how the adaptive immunity by initiating an antigen-specific response can compensate, suppress and activate innate responses at the site of tissue antigen. Here we discuss recent advances in our understanding of the adaptive control of immune effector functions in various pathological and physiological conditions. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Shanker, Anil] NCI, Expt Immunol Lab, Canc & Inflammat Program, SAIC Frederick,NIH, Frederick, MD 21702 USA.
[Shanker, Anil] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Shanker, A (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, SAIC Frederick,NIH, POB B,Bldg 560,Room 31-27, Frederick, MD 21702 USA.
EM shankera@mail.nih.gov
OI Shanker, Anil/0000-0001-6372-3669
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
Research was supported [in part] by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.; The author thanks Francesco M. Marincola
(Clinical Center, NIH), Gonzalo de la Rosa (NCI-Frederick) and Susan L
Swain (Trudeau Institute, NY) for critical reading of the manuscript and
helpful suggestions.
NR 68
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U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD JUL 8
PY 2010
VL 131
IS 2
BP 107
EP 112
DI 10.1016/j.imlet.2010.04.002
PG 6
WC Immunology
SC Immunology
GA 622YR
UT WOS:000279703800001
PM 20394777
ER
PT J
AU Ferreira, RS
Simeonov, A
Jadhav, A
Eidam, O
Mott, BT
Keiser, MJ
McKerrow, JH
Maloney, DJ
Irwin, JJ
Shoichet, BK
AF Ferreira, Rafaela S.
Simeonov, Anton
Jadhav, Ajit
Eidam, Oliv
Mott, Bryan T.
Keiser, Michael J.
McKerrow, James H.
Maloney, David J.
Irwin, John J.
Shoichet, Brian K.
TI Complementarity Between a Docking and a High-Throughput Screen in
Discovering New Cruzain Inhibitors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PROTEIN-LIGAND BINDING; MOLECULAR DOCKING; PROMISCUOUS INHIBITORS;
CYSTEINE PROTEASE; COMPOUND LIBRARIES; TRYPANOSOMA-CRUZI; SCORING
FUNCTIONS; FALSE POSITIVES; IDENTIFICATION; AGGREGATION
AB Virtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On work up, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the Use-positives to which both techniques are individually prone.
C1 [Simeonov, Anton; Jadhav, Ajit; Mott, Bryan T.; Maloney, David J.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Ferreira, Rafaela S.] Univ Calif San Francisco, Grad Program Chem & Chem Biol, San Francisco, CA 94158 USA.
[Ferreira, Rafaela S.; Eidam, Oliv; Keiser, Michael J.; Irwin, John J.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
[Ferreira, Rafaela S.; McKerrow, James H.] Univ Calif San Francisco, Sandler Ctr Basic Res Parasit Dis, San Francisco, CA 94158 USA.
RP Simeonov, A (reprint author), NIH, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov; shoichet@cgl.ucsf.edu
RI Ferreira, Rafaela/L-9841-2014; Keiser, Michael/F-2825-2016;
OI Ferreira, Rafaela/0000-0003-3324-0601; Keiser,
Michael/0000-0002-1240-2192; Irwin, John/0000-0002-1195-6417
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; NHGRI; NIH [GM59957]; Sandler Center for
Basic Research in Parasitic Diseases
FX We thank Julie Zorn for help with mass spectrometry. This research was
supported in part by the Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research and by the Intramural
Research Program of NHGRI, NIH, by NIH grant GM59957 (to B.K.S.), and by
the Sandler Center for Basic Research in Parasitic Diseases (to J.H.M.).
We thank OpenEye Scientific Software for software licenses including
Omega and OE-Chem.
NR 58
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U1 2
U2 33
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 JUL 8
PY 2010
VL 53
IS 13
BP 4891
EP 4905
DI 10.1021/jm100488w
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 617LM
UT WOS:000279282300007
PM 20540517
ER
PT J
AU Kim, HS
Wainer, IW
AF Kim, Hee Seung
Wainer, Irving W.
TI Simultaneous analysis of liposomal doxorubicin and doxorubicin using
capillary electrophoresis and laser induced fluorescence
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article; Proceedings Paper
CT 20th International Symposium on Pharmaceutical and Biomedical Analysis
CY MAR 01-04, 2009
CL Agra, INDIA
DE Doxorubicin; Liposomal doxorubicin; Capillary electrophoresis; Laser
induced fluorescence; Stability
ID BREAST-CANCER; SUBCELLULAR-FRACTIONS; PHARMACOKINETICS; TLC-D99; MYOCET
AB A method based on a capillary electrophoresis with laser induced fluorescence detection was developed and validated for simultaneous separation of doxorubicin (DOX) and liposomal encapsulated DOX The separation was accomplished using a fused silica capillary (60 cm in total length, 75 mu m I.D.) and potassium phosphate buffer [12.5 mM, pH 7.4] as the running buffer. The effect of sample preparation conditions on maintaining liposomal integrity was also investigated. The limit of detection for DOX was 0.1 mu g/ml and the precision and accuracy of CE/LIF method was within the ranges of FDA guidelines. The validated method was successfully used to quantify DOX in human plasma using a direct injection of a 4-fold dilution of spiked liposomal DOX in human plasma. (C) 2009 Published by Elsevier B.V.
C1 [Kim, Hee Seung] NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Kim, HS (reprint author), NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM hskjay@hotmail.com
FU Intramural NIH HHS [Z01 AG000297-06]
NR 12
TC 18
Z9 18
U1 2
U2 42
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JUL 8
PY 2010
VL 52
IS 3
SI SI
BP 372
EP 376
DI 10.1016/j.jpba.2009.06.028
PG 5
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 572NA
UT WOS:000275838300007
PM 19625153
ER
PT J
AU Moaddel, R
Musyimi, HK
Sanghvi, M
Bashore, C
Frazier, CR
Khadeer, M
Bhatia, P
Wainer, IW
AF Moaddel, Ruin
Musyimi, Harrison K.
Sanghvi, Mitesh
Bashore, Charlene
Frazier, Chester R.
Khadeer, Mohammad
Bhatia, Prateek
Wainer, Irving W.
TI Synthesis and characterization of a cellular membrane affinity
chromatography column containing histamine 1 and P2Y(1) receptors: A
multiple G-protein coupled receptor column
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article; Proceedings Paper
CT 20th International Symposium on Pharmaceutical and Biomedical Analysis
CY MAR 01-04, 2009
CL Agra, INDIA
DE Affinity chromatography; Drug discovery; Receptor screening;
Anti-histamines; Membrane receptors
ID STATIONARY PHASES
AB A cellular membrane affinity chromatography (CMAC) column has been created using cellular membrane fragments from a 1321N1 cell line stably transfected with the P2Y(1) receptor. The CMAC(1321N1(P2Y1)) column contained functional P2Y(1) and histamine I receptors, which independently bound receptor-specific ligands. The data obtained with the CMAC(1321N1(P2Y1)) column demonstrate that multiple-G-protein coupled receptor (GPCR) columns can be developed and used to probe interactions with the immobilized receptors and that endogenously expressed GPCRs can be used to create CMAC columns. The results also establish that the histamine 1 receptor can be immobilized with retention of ligand-specific binding. Published by Elsevier B.V.
C1 [Moaddel, Ruin; Musyimi, Harrison K.; Sanghvi, Mitesh; Bashore, Charlene; Frazier, Chester R.; Khadeer, Mohammad; Bhatia, Prateek; Wainer, Irving W.] NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Moaddel, R (reprint author), NIA, NIH, Biomed Res Ctr 8B131, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM moaddelru@mail.nih.gov
RI Sanghvi, Mitesh/C-6740-2013
FU Intramural NIH HHS [ZIA AG000295-13, Z99 AG999999]
NR 11
TC 9
Z9 9
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JUL 8
PY 2010
VL 52
IS 3
SI SI
BP 416
EP 419
DI 10.1016/j.jpba.2009.06.035
PG 4
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 572NA
UT WOS:000275838300014
PM 19608372
ER
PT J
AU Doyle, AD
Yamada, KM
AF Doyle, Andrew D.
Yamada, Kenneth M.
TI CELL BIOLOGY Sensing tension
SO NATURE
LA English
DT Editorial Material
ID FORCE; BINDING; SENSOR
C1 [Doyle, Andrew D.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Doyle, AD (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM andrew.doyle@nih.gov; kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
NR 10
TC 5
Z9 5
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 192
EP 193
DI 10.1038/466192a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800024
PM 20613830
ER
PT J
AU Manolio, TA
AF Manolio, Teri A.
TI Genomewide Association Studies and Assessment of the Risk of Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID WIDE ASSOCIATION; MACULAR DEGENERATION; SUSCEPTIBILITY LOCI;
PROSTATE-CANCER; COMMON VARIANTS; GENETIC-VARIANTS; CROHNS-DISEASE;
BREAST-CANCER; HAPLOTYPE MAP; LARGE-SCALE
C1 NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
RP Manolio, TA (reprint author), NHGRI, Off Populat Genom, Bldg 31,Rm 4B-09,31 Ctr Dr,MSC 2152, Bethesda, MD 20892 USA.
EM manolio@nih.gov
NR 74
TC 624
Z9 651
U1 11
U2 85
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 JUL 8
PY 2010
VL 363
IS 2
BP 166
EP 176
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 621JY
UT WOS:000279574100009
PM 20647212
ER
PT J
AU Santhanam, AN
Baker, AR
Hegamyer, G
Kirschmann, DA
Colburn, NH
AF Santhanam, A. N.
Baker, A. R.
Hegamyer, G.
Kirschmann, D. A.
Colburn, N. H.
TI Pdcd4 repression of lysyl oxidase inhibits hypoxia-induced breast cancer
cell invasion
SO ONCOGENE
LA English
DT Article
DE PDCD4; lysyl oxidase; breast cancer; hypoxia
ID TUMOR-SUPPRESSOR PDCD4; INITIATION-FACTOR 4A; NF-KAPPA-B; TRANSFORMATION
SUPPRESSOR; PROTEIN PDCD4; INDUCIBLE FACTOR-1-ALPHA; EUKARYOTIC
TRANSLATION; AP-1 TRANSACTIVATION; COLORECTAL-CANCER; GENE-EXPRESSION
AB Metastasis to bone, liver and lungs is the primary cause of death in breast cancer patients. Our studies have revealed that the novel tumor suppressor Pdcd4 inhibits breast cancer cell migration and invasion in vitro. Loss of Pdcd4 in human nonmetastatic breast cancer cells increased the expression of lysyl oxidase (LOX) mRNA. LOX is a hypoxia-inducible amine oxidase, the activity of which enhances breast cancer cell invasion in vitro and in vivo. Specific inhibition of LOX activity by beta-aminopropionitrile or small interfering RNA decreased the invasiveness of T47D and MCF7 breast cancer cells attenuated for Pdcd4 function. Most significantly, loss of Pdcd4 augments hypoxia induction of LOX as well. Conversely, overexpression of Pdcd4 significantly reversed the hypoxia induction of LOX expression in T47D cells attenuated for Pdcd4. However, Pdcd4 did not affect hypoxia-inducible factor-1 (HIF-1) protein expression or HIF-1-responsive element-luciferase activity in response to hypoxia, suggesting that Pdcd4 regulation of LOX occurs through an HIF-independent mechanism. Nevertheless, the loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness. Oncogene (2010) 29, 3921-3932; doi:10.1038/onc.2010.158; published online 24 May 2010
C1 [Santhanam, A. N.; Baker, A. R.; Hegamyer, G.; Colburn, N. H.] NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Kirschmann, D. A.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Childrens Mem Res Ctr,Canc Biol & Epigen Program, Chicago, IL 60611 USA.
RP Santhanam, AN (reprint author), NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Boyles St, Frederick, MD 21702 USA.
EM santhanama@ncifcrf.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Drs Giovanni Melillo and Annamaria Rapisarda (Tumor Hypoxia
Laboratory, NCI-Frederick) for helpful suggestions and for the use of
reagents and hypoxia chambers. We also thank members of the Gene
Regulation Section, Laboratory of Cancer Prevention, for helpful
discussions. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 62
TC 31
Z9 36
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUL 8
PY 2010
VL 29
IS 27
BP 3921
EP 3932
DI 10.1038/onc.2010.158
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 621SL
UT WOS:000279603200005
PM 20498644
ER
PT J
AU Merrins, MJ
Fendler, B
Zhang, M
Sherman, A
Bertram, R
Satin, LS
AF Merrins, Matthew J.
Fendler, Bernard
Zhang, Min
Sherman, Arthur
Bertram, Richard
Satin, Leslie S.
TI Metabolic Oscillations in Pancreatic Islets Depend on the Intracellular
Ca2+ Level but Not Ca2+ Oscillations
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PULSATILE INSULIN-SECRETION; CYTOPLASMIC FREE CA2+; MOUSE BETA-CELLS;
GLUCOSE-INDUCED OSCILLATIONS; INDUCED ELECTRICAL-ACTIVITY;
OXYGEN-CONSUMPTION; ATP/ADP RATIO; K+ CHANNELS; IN-VIVO; CALCIUM
OSCILLATIONS
AB Plasma insulin is pulsatile and reflects oscillatory insulin secretion from pancreatic islets. Although both islet Ca2+ and metabolism oscillate, there is disagreement over their interrelationship, and whether they can be dissociated. In some models of islet oscillations, Ca2+ must oscillate for metabolic oscillations to occur, whereas in others metabolic oscillations can occur without Ca2+ oscillations. We used NAD(P)H fluorescence to assay oscillatory metabolism in mouse islets stimulated by 11.1 mM glucose. After abolishing Ca2+ oscillations with 200 mu M diazoxide, we observed that oscillations in NAD(P)H persisted in 34% of islets (n = 101). In the remainder of the islets (66%) both Ca2+ and NAD(P)H oscillations were eliminated by diazoxide. However, in most of these islets NAD(P)H oscillations could be restored and amplified by raising extracellular KCl, which elevated the intracellular Ca2+ level but did not restore Ca2+ oscillations. Comparatively, we examined islets from ATP-sensitive K+ (K-ATP) channel-deficient SUR1(-/-) mice. Again NAD(P)H oscillations were evident even though Ca2+ and membrane potential oscillations were abolished. These observations are predicted by the dual oscillator model, in which intrinsic metabolic oscillations and Ca2+ feedback both contribute to the oscillatory islet behavior, but argue against other models that depend on Ca2+ oscillations for metabolic oscillations to occur.
C1 [Merrins, Matthew J.; Satin, Leslie S.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Merrins, Matthew J.; Satin, Leslie S.] Univ Michigan, Sch Med, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA.
[Fendler, Bernard] Florida State Univ, Dept Phys, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
[Zhang, Min] Virginia Commonwealth Univ, Dept Pharmacol, Richmond, VA USA.
[Sherman, Arthur] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Satin, LS (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
EM lsatin@umich.edu
OI Merrins, Matthew J./0000-0003-1599-9227
FU National Institutes of Health [RO1-DK46409]; National Institute of
Diabetes and Digestive and Kidney Diseases [F32-DK085960]; American
Heart Association [AHA-0715126]; National Science Foundation
[DMS-0613179, DMS-0917664]
FX This work is supported by the National Institutes of Health (RO1-DK46409
to L.S.S.), the National Institute of Diabetes and Digestive and Kidney
Diseases (F32-DK085960 to M.J.M.), the American Heart Association
(AHA-0715126 to B.F.), and the National Science Foundation (DMS-0613179;
DMS-0613179 and DMS-0917664 to R.B.).
NR 57
TC 27
Z9 27
U1 0
U2 5
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 JUL 7
PY 2010
VL 99
IS 1
BP 76
EP 84
DI 10.1016/j.bpj.2010.04.012
PG 9
WC Biophysics
SC Biophysics
GA 623EL
UT WOS:000279720800014
PM 20655835
ER
PT J
AU Nestorovich, EM
Karginov, VA
Berezhkovskii, AM
Bezrukov, SM
AF Nestorovich, Ekaterina M.
Karginov, Vladimir A.
Berezhkovskii, Alexander M.
Bezrukov, Sergey M.
TI Blockage of Anthrax PA63 Pore by a Multicharged High-Affinity Toxin
Inhibitor
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES;
PROTECTIVE ANTIGEN CHANNEL; VOLTAGE-DEPENDENT BLOCK; SINGLE-CHANNEL;
PROTEIN TRANSLOCATION; CRYSTAL-STRUCTURE; LETHAL TOXIN; ACIDIFICATION
AB Single channels of Bacillus anthracis protective antigen, PA(63), were reconstituted into planar lipid membranes and their inhibition by cationic aminopropylthio-beta-cyclodextrin, AmPr beta CD, was studied. The design of the highly efficient inhibitor, the sevenfold symmetrical cyclodextrin molecule chemically modified to add seven positive charges, was guided by the symmetry and predominantly negative charge of the PA(63) pore. The protective action of this compound has been demonstrated earlier at both single-molecule and whole-organism levels. In this study, using noise analysis, statistics of time-resolved single-channel closure events, and multichannel measurements, we find that AmPr beta CD action is bimodal. The inhibitor, when added to the cis side of the membrane, blocks the channel reversibly. At high salt concentrations, the AmPr beta CD blockage of the channel is well described as a two-state Markov process, in which both the on- and off-rates are functions of the salt concentration, whereas the applied voltage affects only the off-rate. At salt concentrations smaller than 1.5 M, the second mode of AmPr beta CD action on the channel is discovered: addition of the inhibitor enhances voltage gating, making the closed states of the channel more favorable. The effect depends on the lipid composition of the membrane.
C1 [Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, Bethesda, MD USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Karginov, Vladimir A.] Innovat Biol, Herndon, VA USA.
RP Nestorovich, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, Bethesda, MD USA.
EM nestoroe@mail.nih.gov
FU National Institutes of Health; Center for Information Technology; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases
(NIAID)
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, the Center for Information Technology,
and the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, and the National Institute of Allergy and Infectious
Diseases (NIAID) Intramural Biodefense Research grant for institutes
other than NIAID. V.A.K. is an employee and shareholder of Innovative
Biologics, Inc.
NR 37
TC 31
Z9 31
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JUL 7
PY 2010
VL 99
IS 1
BP 134
EP 143
DI 10.1016/j.bpj.2010.03.070
PG 10
WC Biophysics
SC Biophysics
GA 623EL
UT WOS:000279720800020
PM 20655841
ER
PT J
AU McHale, K
Mabuchi, H
AF McHale, Kevin
Mabuchi, Hideo
TI Intramolecular Fluorescence Correlation Spectroscopy in a Feedback
Tracking Microscope
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID 3-DIMENSIONAL PARTICLE TRACKING; PHOTON STATISTICS; MOLECULE;
FLUCTUATIONS; DYNAMICS; FCS
AB We derive the statistics of the signals generated by shape fluctuations of large molecules studied by feedback tracking microscopy. We account for the influence of intramolecular dynamics on the response of the tracking system and derive a general expression for the fluorescence autocorrelation function that applies when those dynamics are linear. We show that in comparison to traditional fluorescence correlation spectroscopy, tracking provides enhanced sensitivity to translational diffusion, molecular size, heterogeneity, and long-timescale decays. We demonstrate our approach using a three-dimensional tracking microscope to study genomic A-phage DNA molecules with various fluorescence label configurations.
C1 [McHale, Kevin; Mabuchi, Hideo] Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA.
[McHale, Kevin] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP McHale, K (reprint author), Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA.
EM mchalek@gmail.com
NR 31
TC 1
Z9 1
U1 1
U2 6
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 JUL 7
PY 2010
VL 99
IS 1
BP 313
EP 322
DI 10.1016/j.bpj.2010.03.045
PG 10
WC Biophysics
SC Biophysics
GA 623EL
UT WOS:000279720800039
PM 20655860
ER
PT J
AU Ellacott, KLJ
Morton, GJ
Woods, SC
Tso, P
Schwartz, MW
AF Ellacott, Kate L. J.
Morton, Gregory J.
Woods, Stephen C.
Tso, Patrick
Schwartz, Michael W.
TI Assessment of Feeding Behavior in Laboratory Mice
SO CELL METABOLISM
LA English
DT Article
ID BODY-WEIGHT; GLUCOSE-HOMEOSTASIS; SPEED CONGENICS; ENERGY-BALANCE;
C57BL/6J MICE; FOOD-INTAKE; MOUSE; OBESITY; LEPTIN; RATS
AB The global obesity epidemic has heightened the need for an improved understanding of how body weight is controlled, and research using mouse models is critical to this effort. In this perspective, we provide a conceptual framework for investigation of feeding behavior in this species, with an emphasis on factors that influence study design, data interpretation, and relevance to feeding behavior in humans. Although we focus on the mouse, the principles presented can be applied to most other animal models. This document represents the current consensus view of investigators from the National Institutes of Health (NIH)-funded Mouse Metabolic Phenotyping Centers (MMPCs).
C1 [Ellacott, Kate L. J.] Vanderbilt Univ, Med Ctr, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
[Ellacott, Kate L. J.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Mouse Metab Phenotyping Ctr, Seattle, WA 98109 USA.
[Morton, Gregory J.; Schwartz, Michael W.] Diabet & Obes Ctr Excellence, Dept Med, Seattle, WA 98109 USA.
[Woods, Stephen C.; Tso, Patrick] Univ Cincinnati, Mouse Metab Phenotyping Ctr, Cincinnati, OH 45267 USA.
[Woods, Stephen C.; Tso, Patrick] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA.
[Woods, Stephen C.; Tso, Patrick] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA.
RP Ellacott, KLJ (reprint author), Vanderbilt Univ, Med Ctr, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
EM kate.ellacott@vanderbilt.edu
RI Schwartz, Michael/H-9950-2012;
OI Ellacott, Kate/0000-0001-5261-7465
FU NIH [U24 DK059637]
FX The authors thank members of the MMPC for their helpful discussion and
careful reading of the manuscript. The MMPC is funded by NIH grant U24
DK059637. M.W.S. is a member of a scientific advisory board for Pfizer,
Inc.
NR 50
TC 46
Z9 46
U1 1
U2 8
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 JUL 7
PY 2010
VL 12
IS 1
BP 10
EP 17
DI 10.1016/j.cmet.2010.06.001
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 623PI
UT WOS:000279753900005
PM 20620991
ER
PT J
AU Tang, WK
Li, DY
Li, CC
Esser, L
Dai, RM
Guo, LA
Xia, D
AF Tang, Wai Kwan
Li, Dongyang
Li, Chou-chi
Esser, Lothar
Dai, Renming
Guo, Liang
Xia, Di
TI A novel ATP-dependent conformation in p97 N-D1 fragment revealed by
crystal structures of disease-related mutants
SO EMBO JOURNAL
LA English
DT Article
DE p97; VCP; IBMPFD; structure; conformational change
ID INCLUSION-BODY MYOPATHY; VALOSIN-CONTAINING PROTEIN; AAA-ATPASE;
FRONTOTEMPORAL DEMENTIA; PAGET-DISEASE; CLPAP PROTEASE; VCP MUTATIONS;
UBIQUITIN; BINDING; P97/VCP
AB Mutations in p97, a major cytosolic AAA (ATPases associated with a variety of cellular activities) chaperone, cause inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). IBMPFD mutants have single amino-acid substitutions at the interface between the N-terminal domain (N-domain) and the adjacent AAA domain (D1), resulting in a reduced affinity for ADP. The structures of p97 N-D1 fragments bearing IBMPFD mutations adopt an atypical N-domain conformation in the presence of Mg(2+) center dot ATP gamma S, which is reversible by ADP, showing for the first time the nucleotide-dependent conformational change of the N-domain. The transition from the ADP-to the ATP gamma S-bound state is accompanied by a loop-to-helix conversion in the N-D1 linker and by an apparent re-ordering in the N-terminal region of p97. X-ray scattering experiments suggest that wild-type p97 subunits undergo a similar nucleotide-dependent N-domain conformational change. We propose that IBMPFD mutations alter the timing of the transition between nucleotide states by destabilizing the ADP-bound form and consequently interfere with the interactions between the N-domains and their substrates. The EMBO Journal (2010) 29, 2217-2229. doi:10.1038/emboj.2010.104; Published online 28 May 2010
C1 [Tang, Wai Kwan; Li, Dongyang; Esser, Lothar; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Li, Chou-chi; Dai, Renming] NCI, Intramural Res Support Program, SAIC Frederick, NIH, Frederick, MD 21701 USA.
[Guo, Liang] IIT, BioCAT Adv Photon Source, Argonne Natl Lab, Argonne, IL USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 2122C, Bethesda, MD 20892 USA.
EM dixia@helix.nih.gov
RI Tang, Wai Kwan/A-6158-2012
FU NIH, National Cancer Institute, Center for Cancer Research; Natural
Science Foundation of China [30628006]
FX We thank the staff of the SER-CAT beamline at APS, ANL for their
assistance with data collection. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. We acknowledge the Natural Science
Foundation of China (Program 30628006) for its support to the Tongji
University, China and to DX. Our special thanks go to Drs. Susan
Gottesman, Michael Maurizi, and Yihong Ye for critical reading of the
manuscript. We also thank George Leiman for editorial assistance.
NR 46
TC 64
Z9 66
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD JUL 7
PY 2010
VL 29
IS 13
BP 2217
EP 2229
DI 10.1038/emboj.2010.104
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 622AO
UT WOS:000279630600013
PM 20512113
ER
PT J
AU Cummings, DM
Belluscio, L
AF Cummings, Diana M.
Belluscio, Leonardo
TI Continuous Neural Plasticity in the Olfactory Intrabulbar Circuitry
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID UNILATERAL NARIS OCCLUSION; TYROSINE-HYDROXYLASE EXPRESSION; DEPENDENT
SYNAPTIC PLASTICITY; ODOR-DEPRIVED RATS; STRUCTURAL PLASTICITY; GRANULE
CELLS; TUFTED CELLS; BULB; SYSTEM; DEPRIVATION
AB In the mammalian brain each olfactory bulb contains two mirror-symmetric glomerular maps linked through a set of reciprocal intrabulbar projections. These projections connect isofunctional odor columns through synapses in the internal plexiform layer (IPL) to produce an intrabulbar map. Developmental studies show that initially intrabulbar projections broadly target the IPL on the opposite side of the bulb and refine postnatally to their adult precision by 7 weeks of age in an activity-dependent manner (Marks et al., 2006). In this study, we sought to determine the capacity of intrabulbar map to recover its precision after disruption. Using reversible naris closure in both juvenile and adult mice, we distorted the intrabulbar map and then removed the blocks for varying survival periods. Our results reveal that returning normal olfactory experience can indeed drive the re-refinement of intrabulbar projections but requires 9 weeks. Since activity also affects olfactory sensory neurons (OSNs) (Suh et al., 2006), wefurther examined the consequence of activity deprivation on P2-expressing OSNs and their associated glomeruli. Our findings indicate that while naris closure caused a marked decrease in P2-OSN number and P2-glomerular volume, axonal convergence was not lost and both were quickly restored within 3 weeks. By contrast, synaptic contacts within the IPL also decreased with sensory deprivation but required at least 6 weeks to recover. Thus, we conclude that recovery of the glomerular map precedes and likely drives the refinement of the intrabulbar map while IPL contacts recover gradually, possibly setting the pace for intrabulbar circuit restoration.
C1 [Belluscio, Leonardo] NINDS, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Belluscio, L (reprint author), NINDS, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 3A-116,35 Convent Dr,MSC 3703, Bethesda, MD 20892 USA.
EM belluscl@ninds.nih.gov
FU National Institutes of Health-National Institute of Neurological
Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health-National Institute of Neurological
Disorders and Stroke.
NR 46
TC 23
Z9 25
U1 0
U2 4
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 JUL 7
PY 2010
VL 30
IS 27
BP 9172
EP 9180
DI 10.1523/JNEUROSCI.1717-10.2010
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 621MA
UT WOS:000279581700016
PM 20610751
ER
PT J
AU Nguyen, MQ
Marks, CA
Belluscio, L
Ryba, NJP
AF Nguyen, Minh Q.
Marks, Carolyn A.
Belluscio, Leonardo
Ryba, Nicholas J. P.
TI Early Expression of Odorant Receptors Distorts the Olfactory Circuitry
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROTEIN GAMMA-SUBUNIT; SENSORY MAP; MOUSE; NEURONS; SYSTEM; BULB;
PROJECTIONS; REPRESENTATIONS; NEUROGENESIS; GLOMERULI
AB The odor response properties of a mammalian olfactory sensory neuron (OSN) are determined by the tightly regulated expression of a single member of a very large family of odorant receptors (ORs). The OR also plays an important role in focusing the central projections of all OSNs expressing that particular receptor to a pair of stereotypic locations (glomeruli) in each olfactory bulb (OB), thus creating a spatial map of odor responses in the brain. Here we show that when initiated late in neural development, transgenic expression of one OR in almost all OSNs has little influence on the architecture of the OB in mice. In contrast, early OR-transgene expression (mediated by the G gamma 8-promoter) in 50-70% of OSNs grossly distorts the morphology of glomeruli and alters the projection patterns of many residual OSNs not expressing the transgene. Interestingly, this disruption of targeting persists in adult animals despite the downregulation of G gamma 8 and transgenic OR expression that occurs as olfactory neurogenesis declines. Indeed, functional imaging studies reveal a dramatic decrease in the complexity of responses to odorants in adult G gamma 8-transgenic OR mice. Thus, we show that initiation of transgenic OR expression early in the development of OSNs, rather than just the extent of transgene expression, determines its effectiveness at modifying OB anatomy and function. Together, these data imply that OR-expression timing needs to be very tightly controlled to achieve the precise wiring and function of the mammalian olfactory system.
C1 [Nguyen, Minh Q.; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
[Marks, Carolyn A.; Belluscio, Leonardo] NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA.
[Marks, Carolyn A.] Karolinska Inst, Div Mol Neurobiol, Dept Neurosci, SE-17177 Stockholm, Sweden.
RP Nguyen, MQ (reprint author), Bldg 49,Room 1A16,49 Convent Dr, Bethesda, MD 20892 USA.
EM mn143p@nih.gov
FU National Institutes of Health; National Institute of Dental and
Craniofacial Research; National Institute of Neurological Disorders and
Stroke
FX This research was supported by the intramural research program of the
National Institutes of Health and National Institute of Dental and
Craniofacial Research (N.J.P.R.), and National Institute of Neurological
Disorders and Stroke (L.B.). We thank Mark Hoon and members of our
laboratories for valuable comments. M.Q.N. designed the study, performed
experiments, analyzed data, and wrote the manuscript; C. A. M. performed
experiments and analyzed data; L. B. designed the study and analyzed
data; and N.J.P.R. designed the study, analyzed data, and wrote the
manuscript.
NR 32
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U1 0
U2 0
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 JUL 7
PY 2010
VL 30
IS 27
BP 9271
EP 9279
DI 10.1523/JNEUROSCI.1502-10.2010
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 621MA
UT WOS:000279581700027
PM 20610762
ER
PT J
AU Plaza, A
Keffer, JL
Bifulco, G
Lloyd, JR
Bewley, CA
AF Plaza, Alberto
Keffer, Jessica L.
Bifulco, Giuseppe
Lloyd, John R.
Bewley, Carole A.
TI Chrysophaentins A-H, Antibacterial Bisdiarylbutene Macrocycles That
Inhibit the Bacterial Cell Division Protein FtsZ
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MARINE ACTINOMYCETE; ESCHERICHIA-COLI; SMALL-MOLECULE; ANTIBIOTICS;
TARGET; INSIGHTS
AB Eight new antimicrobial natural products named chrysophaentins A-H belonging to a new structural class have been isolated from the marine chrysophyte alga Chtysophaeum taylori. Their structures were determined by extensive 2D NMR and MS techniques and are characterized by the presence of two polyhalogenated, polyoxygenated omega,omega'-diarylbutene units connected by two ether bonds to form the suite of macrocyclic natural products Chrysophaentin A, the most potent of these antibiotics, inhibited the growth of clinically relevant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MIC(50) 1 5 +/- 0.7 mu g/mL), multidrug-resistant S aureus (1 3 +/- 0.4 mu g/mL), and vancomycin-resistant Enterococcus faecium (MIC(50) 2.9 +/- 0.8 mu g/mL) In vitro enzyme assays and transmission electron microscopy showed chrysophaentin A to inhibit the GTPase activity of the bacterial cytoskeletal protein FtsZ with an IC(50) value of 6 7 +/- 1.7 mu g/mL, as well as GTP-induced formation of FtsZ protofilaments. Saturation Transfer Difference (STD) NMR experiments further confirmed chrysophaentin A binds to FtsZ, and NMR competition experiments with GTP gamma S showed chrysophaentin A and GTP to bind competitively to FtsZ Last, molecular docking simulations provided a low energy model in which chrysophaentin A binds in and occludes a large portion of the GTP binding site of FtsZ in a manner that is consistent with the binding epitope determined by STD NMR.
C1 [Plaza, Alberto; Keffer, Jessica L.; Lloyd, John R.; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Bifulco, Giuseppe] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Salerno, Italy.
RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RI Bifulco, Giuseppe/A-5413-2011;
OI Bifulco, Giuseppe/0000-0002-1788-5170; zaraat,
javad/0000-0001-5341-7481; Keffer, Jessica/0000-0002-0302-3588
FU NIH; Office of the Director, NIH
FX We thank K. Thurber and R Tycko for assistance with and use of the
Morgani TEM, M Bewley and M Clore for help with collections, and W.
Fenical and W Gerwick for helpful discussions on chrysophyte algae. This
work was supported by the NIH Intramural Research Program (NIDDK), and
the Intramural AIDS Targeted Antiviral Program, Office of the Director,
NIH (C A.B).
NR 31
TC 44
Z9 47
U1 3
U2 21
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 JUL 7
PY 2010
VL 132
IS 26
BP 9069
EP 9077
DI 10.1021/ja102100h
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 621FP
UT WOS:000279561200064
PM 20536175
ER
PT J
AU Nussenblatt, RB
Meinert, CL
AF Nussenblatt, Robert B.
Meinert, Curtis L.
TI The status of clinical trials: Cause for concern
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
AB Background: Americans see clinical research as important, with over 15 million American residents participating in NIH-sponsored studies in 2008 and growing yearly.
Methods: Documents reporting NIH supported Clinical Research projects were reviewed.
Results: When compared with other studies, the number of interventional Phase III and Phase IV trials have decreased from 20% to 4.4% from 1994-2008.
Conclusions: This finding most likely has occurred for several reasons. One reason is that the physician lacks an infrastructure for designing and carrying out trials. This lack is because of an absence of a coordinated effort to train clinical trialists. It is clear that the Nation needs a more purposeful approach to developing and maintaining the infrastructure for designing and conducting clinical trials. Building it de novo trial by trial is profoundly inefficient, to say nothing about time consuming and error prone.
C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Meinert, Curtis L.] Johns Hopkins Ctr Clin Trials, Baltimore, MD 21205 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
NR 12
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 7
PY 2010
VL 8
AR 65
DI 10.1186/1479-5876-8-65
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 629AO
UT WOS:000280166600001
PM 20609234
ER
PT J
AU Zhao, HY
Brown, PH
Balbo, A
Fernandez-Alonso, MD
Polishchuck, N
Chaudhry, C
Mayer, ML
Ghirlando, R
Schuck, P
AF Zhao, Huaying
Brown, Patrick H.
Balbo, Andrea
del Carmen Fernandez-Alonso, Maria
Polishchuck, Natasha
Chaudhry, Charu
Mayer, Mark L.
Ghirlando, Rodolfo
Schuck, Peter
TI Accounting for Solvent Signal Offsets in the Analysis of Interferometric
Sedimentation Velocity Data
SO MACROMOLECULAR BIOSCIENCE
LA English
DT Article
DE analytical ultracentrifugation; modeling; nanoparticles; rayleigh
interferometry; size-distribution
ID SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; LAMM
EQUATION; PROTEINS; BOUNDARY; BINDING; MACROMOLECULES; DISTRIBUTIONS;
COEFFICIENTS; AGGREGATION
AB Sedimentation velocity (SV) analytical ultracentrifugation has re-emerged as an important tool in the characterization of biological macromolecules and nanoparticles. The computational analysis of the evolution of the macromolecular concentration profile allows the characterization of many hydrodynamic and thermodynamic properties of the macromolecules and their interactions. The Rayleigh interference optical system is often the detection method of choice, for its usually superior data quality and the wide applicability of refractive index sensitive detection. However, the interference optical system is also sensitive to the redistribution of co-solvent molecules, which are not of primary experimental interest. In principle, their contribution can be eliminated by an exact geometric and compositional match of the sample solution and the reference solution, achieving the complete optical subtraction of unwanted buffer signals. Unfortunately, in practice, this can often not be perfectly achieved for various reasons, leading to signal offsets arising from unmatched sedimentation of solvent components. If unrecognized, this can lead to significant misfit, accompanied by significant errors in the macromolecular sedimentation parameters. In the present work, we describe an approach of computationally accounting for signals from sedimenting buffer components through explicitly modeling their redistribution with Lamm Equation solutions, implemented in the software SEDFIT. We demonstrate how this can restore the SV analysis to yield a high quality fit of the data and to provide correct macromolecular sedimentation parameters.
C1 [Zhao, Huaying; Brown, Patrick H.; Balbo, Andrea; del Carmen Fernandez-Alonso, Maria; Polishchuck, Natasha; Schuck, Peter] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Chaudhry, Charu; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhao, HY (reprint author), NIBIB, Lab Bioengn & Phys Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaoh3@mail.nih.gov
RI Ghirlando, Rodolfo/A-8880-2009; Zhao, Huaying/F-5716-2012;
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering; National
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute of Child Health and Human Development at the National
Institutes of Health, Bethesda, MD, USA
FX This research was supported by the Intramural Research Programs of the
National Institute of Biomedical Imaging and Bioengineering, National
Institute of Diabetes and Digestive and Kidney Diseases, and the
National Institute of Child Health and Human Development at the National
Institutes of Health, Bethesda, MD, USA.
NR 40
TC 9
Z9 9
U1 0
U2 7
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1616-5187
J9 MACROMOL BIOSCI
JI Macromol. Biosci.
PD JUL 7
PY 2010
VL 10
IS 7
SI SI
BP 736
EP 745
PG 10
WC Biochemistry & Molecular Biology; Materials Science, Biomaterials;
Polymer Science
SC Biochemistry & Molecular Biology; Materials Science; Polymer Science
GA 629ES
UT WOS:000280178400010
PM 20480511
ER
PT J
AU Yap, ML
Mio, K
Ali, S
Minton, A
Kanamaru, S
Arisaka, F
AF Yap, Moh Lan
Mio, Kazuhiro
Ali, Said
Minton, Allen
Kanamaru, Shuji
Arisaka, Fumio
TI Sequential Assembly of the Wedge of the Baseplate of Phage T4 in the
Presence and Absence of Gp11 as Monitored by Analytical
Ultracentrifugation
SO MACROMOLECULAR BIOSCIENCE
LA English
DT Article
DE analytical ultracentrifugation; bacteriophage; c(s) analysis;
self-assembly; tracer sedimentation equilibrium
ID SIZE-DISTRIBUTION ANALYSIS; BACTERIOPHAGE-T4 BASEPLATE; GENETIC-CONTROL;
MORPHOGENESIS; PART
AB The baseplate wedge of bacteriophage T4 consists of seven gene products, namely, gp11, gp10, gp7, gp8, gp6, gp53, and gp25, which assemble strictly in this order with an exception that gp11 can bind to gp10 at any stage of the assembly. In this study, all the seven corresponding genes are expressed as recombinant proteins and all the possible combinations of the gene products are tested for interactions by analytical ultracentrifugation. No interactions among gene products that violate the strict sequential binding are observed except that gp6, gp53, and gp25 interact with each other weakly, but significantly. However, when gp6 is previously bound to the precursor complex, only gp53 binds to gp6 strongly and then gp25 binds to complete the wedge formation. This result indicates that the strict sequential association is based on the conformational change of the complex upon addition of each gene product. The binding constant between subunits in the intermediate complexes is too high to be measured. In fact, the binding of gp11 to gp10 is so tight that the binding constant could not be determined by trace sedimentation equilibrium. Also, no indication of dissociation of the intermediate complexes is found in sedimentation velocity, which indicates that other subunit interactions in the intermediate complexes are also strong. The 43.7 S complex, which formed upon addition of gp53, is a hexamer of the wedge complex and resembles the star-shaped baseplate. The s-value of the baseplate-like complex decreased to 40.6 S upon association with gp11 in spite of the increased molecular weight, which is reflected in the sharper edges of the baseplate-like structure which would have a higher friction.
C1 [Yap, Moh Lan; Ali, Said; Kanamaru, Shuji; Arisaka, Fumio] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
[Mio, Kazuhiro] Natl Inst Adv Ind Sci & Technol, BIRC, Koto Ku, Tokyo 1350064, Japan.
[Minton, Allen] NIDDK, Lab Biochem & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Arisaka, F (reprint author), Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Midori Ku, B-9 4259 Nagatsuta, Yokohama, Kanagawa 2268501, Japan.
EM farisaka@bio.titech.ac.jp
OI Minton, Allen/0000-0001-8459-1247
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan
[16087204, 21770164]
FX This work was supported in part by a Grant-in-Aid for Scientific
Research in Priority Areas (no. 16087204) and a Grant-in-Aid for Young
Scientist (A) (no. 21770164) to S.K. from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan.
NR 18
TC 2
Z9 2
U1 0
U2 1
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1616-5187
EI 1616-5195
J9 MACROMOL BIOSCI
JI Macromol. Biosci.
PD JUL 7
PY 2010
VL 10
IS 7
SI SI
BP 808
EP 813
DI 10.1002/mabi.201000042
PG 6
WC Biochemistry & Molecular Biology; Materials Science, Biomaterials;
Polymer Science
SC Biochemistry & Molecular Biology; Materials Science; Polymer Science
GA 629ES
UT WOS:000280178400019
PM 20593364
ER
PT J
AU Balakumaran, A
Pawelczyk, E
Ren, JQ
Sworder, B
Chaudhry, A
Sabatino, M
Stroncek, D
Frank, JA
Robey, PG
AF Balakumaran, Arun
Pawelczyk, Edyta
Ren, Jiaqiang
Sworder, Brian
Chaudhry, Aneeka
Sabatino, Marianna
Stroncek, David
Frank, Joseph A.
Robey, Pamela G.
TI Superparamagnetic Iron Oxide Nanoparticles Labeling of Bone Marrow
Stromal (Mesenchymal) Cells Does Not Affect Their "Stemness''
SO PLOS ONE
LA English
DT Article
ID IN-VIVO; FERUMOXIDES; TRACKING; OSTEOGENESIS; TRAFFICKING; FIBROBLASTS;
EXPRESSION; MOUSE; MRI
AB Superparamagnetic iron oxide nanoparticles (SPION) are increasingly used to label human bone marrow stromal cells (BMSCs, also called "mesenchymal stem cells'') to monitor their fate by in vivo MRI, and by histology after Prussian blue (PB) staining. SPION-labeling appears to be safe as assessed by in vitro differentiation of BMSCs, however, we chose to resolve the question of the effect of labeling on maintaining the "stemness'' of cells within the BMSC population in vivo. Assays performed include colony forming efficiency, CD146 expression, gene expression profiling, and the "gold standard'' of evaluating bone and myelosupportive stroma formation in vivo in immuncompromised recipients. SPION-labeling did not alter these assays. Comparable abundant bone with adjoining host hematopoietic cells were seen in cohorts of mice that were implanted with SPION-labeled or unlabeled BMSCs. PB+ adipocytes were noted, demonstrating their donor origin, as well as PB+ pericytes, indicative of self-renewal of the stem cell in the BMSC population. This study confirms that SPION labeling does not alter the differentiation potential of the subset of stem cells within BMSCs.
C1 [Balakumaran, Arun; Sworder, Brian; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Pawelczyk, Edyta; Chaudhry, Aneeka; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Ren, Jiaqiang; Sabatino, Marianna; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Balakumaran, A (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
EM balakumarana@nidcr.nih.gov
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; Sworder, Brian/0000-0002-5902-5507
FU National Institute of Dental and Craniofacial Research; Clinical Center,
IRP, NIH, Department of Health and Human Services
FX This study was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research and the Clinical
Center, IRP, NIH, Department of Health and Human Services. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 25
TC 53
Z9 54
U1 1
U2 12
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 JUL 7
PY 2010
VL 5
IS 7
AR e11462
DI 10.1371/journal.pone.0011462
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621OQ
UT WOS:000279589300010
PM 20628641
ER
PT J
AU Noben-Trauth, K
Latoche, JR
Neely, HR
Bennett, B
AF Noben-Trauth, Konrad
Latoche, Joseph R.
Neely, Harold R.
Bennett, Beth
TI Phenotype and Genetics of Progressive Sensorineural Hearing Loss (Snhl1)
in the LXS Set of Recombinant Inbred Strains of Mice
SO PLOS ONE
LA English
DT Article
ID QUANTITATIVE TRAIT LOCI; MOUSE; IMPAIRMENT; INHERITANCE
AB Progressive sensorineural hearing loss is the most common form of acquired hearing impairment in the human population. It is also highly prevalent in inbred strains of mice, providing an experimental avenue to systematically map genetic risk factors and to dissect the molecular pathways that orchestrate hearing in peripheral sensory hair cells. Therefore, we ascertained hearing function in the inbred long sleep (ILS) and inbred short sleep (ISS) strains. Using auditory-evoked brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements, we found that ISS mice developed a high-frequency hearing loss at twelve weeks of age that progressed to lower frequencies by 26 weeks of age in the presence of normal endocochlear potentials and unremarkable inner ear histology. ILS mice exhibited milder hearing loss, showing elevated thresholds and reduced DPOAEs at the higher frequencies by 26 weeks of age. To map the genetic variants that underlie this hearing loss we computed ABR thresholds of 63 recombinant inbred stains derived from the ISS and ILS founder strains. A single locus was linked to markers associated with ISS alleles on chromosome 10 with a highly significant logarithm of odds (LOD) score of 15.8. The 2-LOD confidence interval spans,4 Megabases located at position 54-60 Mb. This locus, termed sensorineural hearing loss 1 (Snhl1), accounts for approximately 82% of the phenotypic variation. In summary, this study identifies a novel hearing loss locus on chromosome 10 and attests to the prevalence and genetic heterogeneity of progressive hearing loss in common mouse strains.
C1 [Noben-Trauth, Konrad; Latoche, Joseph R.; Neely, Harold R.] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD USA.
[Bennett, Beth] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD USA.
EM nobentk@nidcd.nih.gov
FU National Institutes of Health (NIH) [RO1AA08940]; University of Colorado
FX This work was supported by the Intramural Research Program at the
National Institutes of Health (NIH) (KNT), by funds from the University
of Colorado and grants from the NIH (RO1AA08940, BB) www.nih.gov. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 21
TC 13
Z9 13
U1 1
U2 6
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 JUL 7
PY 2010
VL 5
IS 7
AR e11459
DI 10.1371/journal.pone.0011459
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621OQ
UT WOS:000279589300007
PM 20628639
ER
PT J
AU Padayatty, SJ
Sun, AY
Chen, Q
Espey, MG
Drisko, J
Levine, M
AF Padayatty, Sebastian J.
Sun, Andrew Y.
Chen, Qi
Espey, Michael Graham
Drisko, Jeanne
Levine, Mark
TI Vitamin C: Intravenous Use by Complementary and Alternative Medicine
Practitioners and Adverse Effects
SO PLOS ONE
LA English
DT Article
ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; RECOMMENDED DIETARY ALLOWANCE;
ACUTE OXALATE NEPHROPATHY; ACID-INDUCED HEMOLYSIS; TERMINAL HUMAN
CANCER; ASCORBIC-ACID; EXPERIMENTAL POLIOMYELITIS; SUPPLEMENTAL
ASCORBATE; SUPPORTIVE TREATMENT; HYDROGEN-PEROXIDE
AB Background: Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U. S. and associated side effects are unknown.
Methods and Findings: We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U. S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.
Conclusions: High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.
C1 [Padayatty, Sebastian J.; Sun, Andrew Y.; Espey, Michael Graham; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA.
[Chen, Qi; Drisko, Jeanne] Univ Kansas, Med Ctr, Program Integrat Med, Kansas City, KS 66103 USA.
RP Padayatty, SJ (reprint author), NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA.
EM MarkL@intra.niddk.nih.gov
RI Padayatty, Sebastian/A-8581-2012; Chen, Qi/D-8278-2015
OI Padayatty, Sebastian/0000-0001-8758-3170; Chen, Qi/0000-0002-7173-8411
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This work was supported in part by the Intramural Research Program,
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 66
Z9 69
U1 2
U2 12
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 JUL 7
PY 2010
VL 5
IS 7
AR e11414
DI 10.1371/journal.pone.0011414
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621OQ
UT WOS:000279589300002
PM 20628650
ER
PT J
AU Toh, S
Rossouw, JE
Hernan, MA
AF Toh, Sengwee
Rossouw, Jacques E.
Hernan, Miguel A.
TI Menopausal Hormone Therapy and Risk for Cardiovascular Disease in the
WHI Trial RESPONSE
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Toh, Sengwee] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.
[Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA.
[Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Toh, S (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.
RI Toh, Sengwee/D-7567-2017
OI Toh, Sengwee/0000-0002-5160-0810
NR 4
TC 0
Z9 0
U1 0
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 6
PY 2010
VL 153
IS 1
BP 61
EP 62
DI 10.7326/0003-4819-153-1-201007060-00022
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 620GS
UT WOS:000279487700019
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Risk for Venous Thromboembolism in Patients With Superficial Venous
Thrombosis
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 NHLBI, Bethesda, MD 20824 USA.
RP Lauer, MS (reprint author), NHLBI, Bethesda, MD 20824 USA.
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 6
PY 2010
VL 153
IS 1
BP 62
EP 62
DI 10.7326/0003-4819-153-1-201007060-00023
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 620GS
UT WOS:000279487700020
PM 20621914
ER
PT J
AU Chuang, CY
Lord, MS
Melrose, J
Rees, MD
Knox, SM
Freeman, C
Iozzo, RV
Whitelock, JM
AF Chuang, Christine Y.
Lord, Megan S.
Melrose, James
Rees, Martin D.
Knox, Sarah M.
Freeman, Craig
Iozzo, Renato V.
Whitelock, John M.
TI Heparan Sulfate-Dependent Signaling of Fibroblast Growth Factor 18 by
Chondrocyte-Derived Perlecan
SO BIOCHEMISTRY
LA English
DT Article
ID PLATE CHONDROCYTES; BONE-FORMATION; FGF RECEPTORS; PROLIFERATION;
DIFFERENTIATION; CARTILAGE; CHONDROGENESIS; BINDING; MATRIX; CELLS
AB Perlecan is a large multidomain proteoglycan that is essential for normal cartilage development. In this study, perlecan was localized in the pericellular matrix of hypertrophic chondrocytes in developing human cartilage rudiments. Perlecan immunopurified from medium conditioned by cultured human fetal chondrocytes was found to be substituted with heparan sulfate (HS), chondroitin sulfate (CS), and keratan sulfate (KS). Ligand and carbohydrate engagement (LACE) assays demonstrated that immunopurified chondrocyte-derived perlecan formed HS-dependent ternary complexes with fibroblast growth factor (Kin 2 and either FGF receptors (FGFRs) 1 or 3; however, these complexes were not biologically active in the BaF32 cell system. Chondrocyte-derived perlecan also formed HS-dependent ternary complexes with FGF18 and FGFR3. The proliferation of BaF32 cells expressing FGFR3 was promoted by chondrocyte-derived perlecan in the presence of FGF IS, and this activity was reduced by digestion of the HS with either heparinase III or mammalian heparanase. These data suggest that FGF2 and -18 bind to discrete structures on the HS chains attached to chondrocyte-derived perlecan which modulate the growth Factor activities. The presence and activity of mammalian heparanase may be important in the turnover of HS and subsequent signaling required for the establishment and maintenance of functional osteo-chondral junctions in long bone growth.
C1 [Chuang, Christine Y.; Lord, Megan S.; Whitelock, John M.] Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.
[Melrose, James] Univ Sydney, Royal N Shore Hosp, Raymond Purves Res Labs, Kolling Inst Med Res, St Leonards, NSW 2065, Australia.
[Rees, Martin D.] Univ New S Wales, Ctr Vasc Res, Fac Med, Sydney, NSW 2052, Australia.
[Knox, Sarah M.] Natl Inst Dent & Craniofacial Res, Morphogenesis Unit, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Freeman, Craig] Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia.
[Iozzo, Renato V.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Pathol Anat & Cell Biol, Canc Cell Biol & Signaling Program, Philadelphia, PA 19107 USA.
RP Lord, MS (reprint author), Univ New S Wales, Grad Sch Biomed Engn, Level 5,Samuels Bldg, Sydney, NSW 2052, Australia.
EM m.lord@unsw.edu.au
RI Lord, Megan/D-4673-2013;
OI Lord, Megan/0000-0002-0506-9811; Knox, Sarah/0000-0002-7567-083X; Rees,
Martin/0000-0002-3564-5736; Iozzo, Renato/0000-0002-5908-5112
FU Australian Government under the ARC [LP0455407]
FX These studies were supported by the Australian Government under the ARC
Linkage grant scheme (Grant LP0455407).
NR 46
TC 52
Z9 53
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 6
PY 2010
VL 49
IS 26
BP 5524
EP 5532
DI 10.1021/bi1005199
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 616GO
UT WOS:000279197300014
PM 20507176
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Screening Asymptomatic Subjects for Subclinical Atherosclerosis Not So
Obvious
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE screening; prevention; atherosclerosis; imaging
ID RANDOMIZED CONTROLLED-TRIAL; PROSTATE-CANCER; CORONARY CALCIUM;
BREAST-CANCER; MORTALITY; DISEASE; MEN; PREVENTION; EVENTS; TIME
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 25
TC 24
Z9 24
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 6
PY 2010
VL 56
IS 2
BP 106
EP 108
DI 10.1016/j.jacc.2010.01.059
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 617WW
UT WOS:000279313600003
PM 20620725
ER
PT J
AU Levy, MZ
Chavez, FSM
del Carpio, JGC
Vilhena, DA
McKenzie, FE
Plotkin, JB
AF Levy, Michael Z.
Malaga Chavez, Fernando S.
Cornejo del Carpio, Juan G.
Vilhena, Daril A.
McKenzie, F. Ellis
Plotkin, Joshua B.
TI Rational spatio-temporal strategies for controlling a Chagas disease
vector in urban environments
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE disease ecology; vector-borne disease; control theory; Chagas disease;
Triatoma infestans; urban
ID TRIATOMA-INFESTANS HEMIPTERA; TRYPANOSOMA-CRUZI INFECTION; NORTHWESTERN
ARGENTINA; GENETIC ALGORITHMS; POPULATIONS; REINFESTATION; ELIMINATION;
REDUVIIDAE; CHILDREN
AB The rational design of interventions is critical to controlling communicable diseases, especially in urban environments. In the case of the Chagas disease vector Triatoma infestans, successful control is stymied by the return of the insect after the effectiveness of the insecticide wanes. Here, we adapt a genetic algorithm, originally developed for the travelling salesman problem, to improve the spatio-temporal design of insecticide campaigns against T. infestans, in a complex urban environment. We find a strategy that reduces the expected instances of vector return 34-fold compared with the current strategy of sequential insecticide application to spatially contiguous communities. The relative success of alternative control strategies depends upon the duration of the effectiveness of the insecticide, and it shows chaotic fluctuations in response to unforeseen delays in a control campaign. We use simplified models to analyse the outcomes of qualitatively different spatio-temporal strategies. Our results provide a detailed procedure to improve control efforts for an urban Chagas disease vector, as well as general guidelines for improving the design of interventions against other disease agents in complex environments.
C1 [Levy, Michael Z.; Vilhena, Daril A.; Plotkin, Joshua B.] Univ Penn, Dept Biol, Carolyn Lynch Labs 219, Philadelphia, PA 19104 USA.
[Levy, Michael Z.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Levy, Michael Z.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Malaga Chavez, Fernando S.; Cornejo del Carpio, Juan G.] Minist Salud, Direcc Reg, Arequipa, Peru.
RP Levy, MZ (reprint author), Univ Penn, Dept Biol, Carolyn Lynch Labs 219, Philadelphia, PA 19104 USA.
EM mzlevy@gmail.com
RI Plotkin, Joshua/E-6947-2013
FU NIH [K01 AI079162-02, P50 AI074285-03]; Burroughs Wellcome Fund; James
S. McDonnell Foundation; Alfred P. Sloan Foundation; David and Lucile
Packard Foundation; [NIH-NIDDK-08-007]
FX We thank Robert Gilman, Caryn Bern, Eleazar Cordova, Cesar Naquira,
Hector Garcia, Lance Waller, Scott Duke-Sylvester, David Smith, Natalie
Bowman, Cecile Viboud, Rajan Patel, Megan Christenson, Nicole Salemno,
the croquisistas and all who helped on the ground in Arequipa, and
members of the Plotkin lab. Funding for this study came from NIH K01
AI079162-02, NIH P50 AI074285-03 and NIH-NIDDK-08-007. J.B.P. also
acknowledges funding from the Burroughs Wellcome Fund, the James S.
McDonnell Foundation, the Alfred P. Sloan Foundation and the David and
Lucile Packard Foundation.
NR 32
TC 10
Z9 10
U1 0
U2 4
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD JUL 6
PY 2010
VL 7
IS 48
BP 1061
EP 1070
DI 10.1098/rsif.2009.0479
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 600MU
UT WOS:000277991600005
PM 20061346
ER
PT J
AU Stack, JC
Welch, JD
Ferrari, MJ
Shapiro, BU
Grenfell, BT
AF Stack, J. Conrad
Welch, J. David
Ferrari, Matt J.
Shapiro, Beth U.
Grenfell, Bryan T.
TI Protocols for sampling viral sequences to study epidemic dynamics
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE phylodynamics; epidemics; simulation
ID POPULATION-DYNAMICS; MEASLES EPIDEMICS; MOLECULAR EPIDEMIOLOGY;
INFERENCE; MODEL; EVOLUTION; VIRUS; HISTORY; EXTINCTION; SKYLINE
AB With more emphasis being put on global infectious disease monitoring, viral genetic data are being collected at an astounding rate, both within and without the context of a long-term disease surveillance plan. Concurrent with this increase have come improvements to the sophisticated and generalized statistical techniques used for extracting population-level information from genetic sequence data. However, little research has been done on how the collection of these viral sequence data can or does affect the efficacy of the phylogenetic algorithms used to analyse and interpret them. In this study, we use epidemic simulations to consider how the collection of viral sequence data clarifies or distorts the picture, provided by the phylogenetic algorithms, of the underlying population dynamics of the simulated viral infection over many epidemic cycles. We find that sampling protocols purposefully designed to capture sequences at specific points in the epidemic cycle, such as is done for seasonal influenza surveillance, lead to a significantly better view of the underlying population dynamics than do less-focused collection protocols. Our results suggest that the temporal distribution of samples can have a significant effect on what can be inferred from genetic data, and thus highlight the importance of considering this distribution when designing or evaluating protocols and analysing the data collected thereunder.
C1 [Stack, J. Conrad; Ferrari, Matt J.; Shapiro, Beth U.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Welch, J. David] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Stack, J. Conrad; Welch, J. David; Ferrari, Matt J.; Grenfell, Bryan T.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA.
RP Stack, JC (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM stack@psu.edu
OI Shapiro, Beth/0000-0002-2733-7776
FU National Institutes of Health [R01 GM083983-01, R01 GM083603-01]; Bill
and Melinda Gates Foundation; Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX J.C.S., B.S. and B.G. were supported by the National Institutes of
Health (R01 GM083983-01) as was D.W. (R01 GM083603-01). B.G. and M.F.
also were supported by the Bill and Melinda Gates Foundation, and the
RAPIDD programme of the Science and Technology Directorate, Department
of Homeland Security and the Fogarty International Center, National
Institutes of Health.
NR 32
TC 20
Z9 20
U1 1
U2 7
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD JUL 6
PY 2010
VL 7
IS 48
BP 1119
EP 1127
DI 10.1098/rsif.2009.0530
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 600MU
UT WOS:000277991600010
PM 20147314
ER
PT J
AU Dotson, VM
Beydoun, MA
Zonderman, AB
AF Dotson, Vonetta M.
Beydoun, May A.
Zonderman, Alan B.
TI Recurrent depressive symptoms and the incidence of dementia and mild
cognitive impairment
SO NEUROLOGY
LA English
DT Article
ID PRODROMAL ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E GENOTYPE; CARDIOVASCULAR
HEALTH; GERIATRIC DEPRESSION; CLINICAL SYMPTOMS; RISK-FACTORS;
COMMUNITY; SAMPLE; COHORT; BRAIN
AB Objective: A history of depression has been linked to an increased dementia risk. This risk may be particularly high in recurrent depression due to repeated brain insult. We investigated whether there is a dose-dependent relationship between the number of episodes of elevated depressive symptoms (EDS) and the risk for mild cognitive impairment (MCI) and dementia.
Methods: A total of 1,239 older adults from the Baltimore Longitudinal Study of Aging were followed for a median of 24.7 years. Diagnoses of MCI and dementia were made based on prospective data. Participants completed the Center for Epidemiologic Studies Depression Scale at 1- to 2-year intervals and were considered to have an EDS if their score was >= 16. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazards models were conducted to examine the risk of MCI and dementia by number of EDS.
Results: We observed a monotonic increase in risk for all-cause dementia and Alzheimer disease as a function of the number of EDS. Each episode was associated with a 14% increase in risk for all-cause dementia. Having 1 EDS conferred an 87%-92% increase in dementia risk, while having 2 or more episodes nearly doubled the risk. Recurrence of EDS did not increase the risk of incident MCI.
Conclusions: Our findings support the hypothesis that depression is a risk factor for dementia and suggest that recurrent depression is particularly pernicious. Preventing the recurrence of depression in older adults may prevent or delay the onset of dementia. Neurology (R) 2010; 75: 27-34
C1 [Dotson, Vonetta M.; Beydoun, May A.; Zonderman, Alan B.] NIA, NIH, IRP, Baltimore, MD 21224 USA.
RP Dotson, VM (reprint author), Univ Florida, Dept Clin & Hlth Psychol, POB 100165, Gainesville, FL 32610 USA.
EM vonetta@phhp.ufl.edu
RI Dotson, Vonetta/K-6090-2015;
OI Dotson, Vonetta/0000-0002-3043-3320; Zonderman, Alan
B/0000-0002-6523-4778
FU NIH/NIA
FX Supported by the Intramural Research Program of the NIH/NIA.
NR 41
TC 110
Z9 114
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 6
PY 2010
VL 75
IS 1
BP 27
EP 34
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 620HQ
UT WOS:000279490200007
PM 20603482
ER
PT J
AU Bjork, JM
Smith, AR
Chen, G
Hommer, DW
AF Bjork, James M.
Smith, Ashley R.
Chen, Gang
Hommer, Daniel W.
TI Adolescents, Adults and Rewards: Comparing Motivational Neurocircuitry
Recruitment Using fMRI
SO PLOS ONE
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EVENT-RELATED FMRI;
ORBITOFRONTAL CORTEX; BRAIN ACTIVITY; RISK-TAKING; CHILDHOOD; CHILDREN;
REGIONS; ANTICIPATION; NEUROSCIENCE
AB Background: Adolescent risk-taking, including behaviors resulting in injury or death, has been attributed in part to maturational differences in mesolimbic incentive-motivational neurocircuitry, including ostensible oversensitivity of the nucleus accumbens (NAcc) to rewards.
Methodology/Principal Findings: To test whether adolescents showed increased NAcc activation by cues for rewards, or by delivery of rewards, we scanned 24 adolescents (age 12-17) and 24 adults age (22-42) with functional magnetic resonance imaging while they performed a monetary incentive delay (MID) task. The MID task was configured to temporally disentangle potential reward or potential loss anticipation-related brain signal from reward or loss notification-related signal. Subjects saw cues signaling opportunities to win or avoid losing $0, $.50, or $5 for responding quickly to a subsequent target. Subjects then viewed feedback of their trial success after a variable interval from cue presentation of between 6 to 17 s. Adolescents showed reduced NAcc recruitment by reward-predictive cues compared to adult controls in a linear contrast with non-incentive cues, and in a volume-of-interest analysis of signal change in the NAcc. In contrast, adolescents showed little difference in striatal and frontocortical responsiveness to reward deliveries compared to adults.
Conclusions/Significance: In light of divergent developmental difference findings between neuroimaging incentive paradigms (as well as at different stages within the same task), these data suggest that maturational differences in incentive-motivational neurocircuitry: 1) may be sensitive to nuances of incentive tasks or stimuli, such as behavioral or learning contingencies, and 2) may be specific to the component of the instrumental behavior (such as anticipation versus notification).
C1 [Bjork, James M.] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
[Smith, Ashley R.; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Chen, Gang] NIMH, NIH, Bethesda, MD 20892 USA.
RP Bjork, JM (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
EM jbjork@mail.nih.gov
OI Bjork, James/0000-0003-0593-3291; Lauwereyns, Jan/0000-0003-0551-2550
FU National Institute on Alcohol Abuse and Alcoholism
FX This research was sponsored by intramural research funds of the National
Institute on Alcohol Abuse and Alcoholism
(http://www.niaaa.nih.gov/ResearchInformation/IntramuralResearch/AboutDI
CBR/). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 108
Z9 109
U1 4
U2 20
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 JUL 6
PY 2010
VL 5
IS 7
AR e11440
DI 10.1371/journal.pone.0011440
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 620TI
UT WOS:000279522500008
PM 20625430
ER
PT J
AU Kirkness, EF
Haas, BJ
Sun, WL
Braig, HR
Perotti, MA
Clark, JM
Lee, SH
Robertson, HM
Kennedy, RC
Elhaik, E
Gerlach, D
Kriventseva, EV
Elsik, CG
Graur, D
Hill, CA
Veenstra, JA
Walenz, B
Tubio, JMC
Ribeiro, JMC
Rozas, J
Johnston, JS
Reese, JT
Popadic, A
Tojo, M
Raoult, D
Reed, DL
Tomoyasu, Y
Krause, E
Mittapalli, O
Margam, VM
Li, HM
Meyer, JM
Johnson, RM
Romero-Severson, J
VanZee, JP
Alvarez-Ponce, D
Vieira, FG
Aguade, M
Guirao-Rico, S
Anzola, JM
Yoon, KS
Strycharz, JP
Unger, MF
Christley, S
Lobo, NF
Seufferheld, MJ
Wang, NK
Dasch, GA
Struchiner, CJ
Madey, G
Hannick, LI
Bidwell, S
Joardar, V
Caler, E
Shao, RF
Barker, SC
Cameron, S
Bruggner, RV
Regier, A
Johnson, J
Viswanathan, L
Utterback, TR
Sutton, GG
Lawson, D
Waterhouse, RM
Venter, JC
Strausberg, RL
Berenbaum, MR
Collins, FH
Zdobnov, EM
Pittendrigh, BR
AF Kirkness, Ewen F.
Haas, Brian J.
Sun, Weilin
Braig, Henk R.
Perotti, M. Alejandra
Clark, John M.
Lee, Si Hyeock
Robertson, Hugh M.
Kennedy, Ryan C.
Elhaik, Eran
Gerlach, Daniel
Kriventseva, Evgenia V.
Elsik, Christine G.
Graur, Dan
Hill, Catherine A.
Veenstra, Jan A.
Walenz, Brian
Tubio, Jose Manuel C.
Ribeiro, Jose M. C.
Rozas, Julio
Johnston, J. Spencer
Reese, Justin T.
Popadic, Aleksandar
Tojo, Marta
Raoult, Didier
Reed, David L.
Tomoyasu, Yoshinori
Krause, Emily
Mittapalli, Omprakash
Margam, Venu M.
Li, Hong-Mei
Meyer, Jason M.
Johnson, Reed M.
Romero-Severson, Jeanne
VanZee, Janice Pagel
Alvarez-Ponce, David
Vieira, Filipe G.
Aguade, Montserrat
Guirao-Rico, Sara
Anzola, Juan M.
Yoon, Kyong S.
Strycharz, Joseph P.
Unger, Maria F.
Christley, Scott
Lobo, Neil F.
Seufferheld, Manfredo J.
Wang, NaiKuan
Dasch, Gregory A.
Struchiner, Claudio J.
Madey, Greg
Hannick, Linda I.
Bidwell, Shelby
Joardar, Vinita
Caler, Elisabet
Shao, Renfu
Barker, Stephen C.
Cameron, Stephen
Bruggner, Robert V.
Regier, Allison
Johnson, Justin
Viswanathan, Lakshmi
Utterback, Terry R.
Sutton, Granger G.
Lawson, Daniel
Waterhouse, Robert M.
Venter, J. Craig
Strausberg, Robert L.
Berenbaum, May R.
Collins, Frank H.
Zdobnov, Evgeny M.
Pittendrigh, Barry R.
TI Genome sequences of the human body louse and its primary endosymbiont
provide insights into the permanent parasitic lifestyle
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID SUCKING LICE PHTHIRAPTERA; DNA-BINDING PROTEIN; DROSOPHILA-MELANOGASTER;
APIS-MELLIFERA; MOLECULAR EVOLUTION; HONEY-BEE; INSECTICIDE RESISTANCE;
ANOPHELES-GAMBIAE; PEDICULUS-HUMANUS; EPIDEMIC TYPHUS
AB As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.
C1 [Sun, Weilin; Robertson, Hugh M.; Li, Hong-Mei; Johnson, Reed M.; Berenbaum, May R.; Pittendrigh, Barry R.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA.
[Kirkness, Ewen F.; Haas, Brian J.; Walenz, Brian; Hannick, Linda I.; Bidwell, Shelby; Joardar, Vinita; Caler, Elisabet; Johnson, Justin; Viswanathan, Lakshmi; Utterback, Terry R.; Sutton, Granger G.; Venter, J. Craig; Strausberg, Robert L.] J Craig Venter Inst, Rockville, MD 20850 USA.
[Braig, Henk R.] Bangor Univ, Sch Biol Sci, Bangor LL57 2UW, Gwynedd, Wales.
[Perotti, M. Alejandra] Univ Reading, Sch Biol Sci, Reading RG6 6AS, Berks, England.
[Clark, John M.; Yoon, Kyong S.; Strycharz, Joseph P.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA.
[Lee, Si Hyeock] Seoul Natl Univ, Dept Agr Biotechnol, Seoul, South Korea.
[Kennedy, Ryan C.; Romero-Severson, Jeanne; Unger, Maria F.; Christley, Scott; Lobo, Neil F.; Madey, Greg; Bruggner, Robert V.; Regier, Allison; Collins, Frank H.] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Kennedy, Ryan C.; Christley, Scott; Madey, Greg; Bruggner, Robert V.; Regier, Allison] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA.
[Elhaik, Eran; Graur, Dan] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
[Gerlach, Daniel; Kriventseva, Evgenia V.; Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
[Gerlach, Daniel; Kriventseva, Evgenia V.; Waterhouse, Robert M.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland.
[Elsik, Christine G.; Reese, Justin T.; Anzola, Juan M.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA.
[Hill, Catherine A.; Margam, Venu M.; Meyer, Jason M.; VanZee, Janice Pagel] Purdue Univ, Dept Entomol, W Lafayette, IN 47907 USA.
[Wang, NaiKuan] Chung Hwa Coll Med Technol, Tainan 700, Taiwan.
[Dasch, Gregory A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Struchiner, Claudio J.] Univ Estado Rio de Janeiro, Inst Social Med, BR-4365 Rio De Janeiro, Brazil.
[Struchiner, Claudio J.] Univ Estado Rio de Janeiro, Escola Nacl Saude Publ Sergio Arouca Fundacao Osw, BR-4365 Rio De Janeiro, Brazil.
[Shao, Renfu; Barker, Stephen C.] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia.
[Cameron, Stephen] Australian Natl Insect Collect & Commonwealth Sci, Canberra, ACT 2601, Australia.
[Lawson, Daniel] European Bioinformat Inst, Hinxton CB10 1SD, Cambs, England.
[Zdobnov, Evgeny M.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Romero-Severson, Jeanne; Unger, Maria F.; Lobo, Neil F.; Collins, Frank H.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Seufferheld, Manfredo J.] Dept Crop Sci, Urbana, IL 61801 USA.
[Rozas, Julio; Alvarez-Ponce, David; Vieira, Filipe G.; Aguade, Montserrat; Guirao-Rico, Sara] Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain.
[Veenstra, Jan A.] Univ Bordeaux, Ctr Neurosci Integrat & Cognit, CNRS, F-33405 Talence, France.
[Tubio, Jose Manuel C.] Univ Santiago de Compostela, Complexo Hosp, Serv Hematol, Santiago De Compostela 15706, Spain.
[Ribeiro, Jose M. C.] NCI, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Johnston, J. Spencer] Texas A&M Univ, Dept Entomol, College Stn, TX 77843 USA.
[Popadic, Aleksandar] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
[Tojo, Marta] Univ Santiago de Compostela, Complexo Hosp, Serv Anat Patol, Santiago De Compostela 15706, Spain.
[Raoult, Didier] Unite Rickettsies, F-13385 Marseille 05, France.
[Reed, David L.] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
[Tomoyasu, Yoshinori; Krause, Emily] Kansas State Univ, Dept Entomol, Manhattan, KS 66502 USA.
[Tomoyasu, Yoshinori; Krause, Emily] Kansas State Univ, Div Biol, Manhattan, KS 66502 USA.
[Mittapalli, Omprakash] Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Entomol, Wooster, OH 44691 USA.
RP Pittendrigh, BR (reprint author), Univ Illinois, Dept Entomol, 320 Morrill Hall, Urbana, IL 61801 USA.
EM pittendr@illinois.edu
RI Elsik, Christine/C-4120-2017; Tomoyasu, Yoshinori/D-3061-2017;
Guirao-Rico, Sara/F-4145-2016; Rozas, Julio/A-1733-2009; Margam,
Venu/E-5876-2010; Romero-Severson, Jeanne/B-5259-2011; Johnson,
Reed/H-3742-2011; Veenstra, Jan/B-4610-2008; Zdobnov,
Evgeny/K-1133-2012; Braig, Henk/I-5477-2013; Struchiner,
Claudio/M-9360-2013; Cameron, Stephen/A-3742-2008; Tubio,
Jose/H-5076-2015; Garrett Vieira, Filipe/B-9464-2015; Waterhouse,
Robert/A-1858-2010
OI Alvarez-Ponce, David/0000-0002-8729-1036; Ribeiro,
Jose/0000-0002-9107-0818; Elsik, Christine/0000-0002-4248-7713;
Tomoyasu, Yoshinori/0000-0001-9824-3454; Dasch,
Gregory/0000-0001-6090-1810; Hannick, Linda/0000-0002-8018-8466;
Gerlach, Daniel/0000-0001-9338-3765; Lawson, Daniel/0000-0001-7765-983X;
Yoon, Kyong/0000-0002-1866-1339; Aguade, Montserrat/0000-0002-3884-7800;
Veenstra, Jan/0000-0002-2783-0018; Guirao-Rico,
Sara/0000-0001-9896-4665; Rozas, Julio/0000-0002-6839-9148;
Romero-Severson, Jeanne/0000-0003-4112-7238; Johnson,
Reed/0000-0002-2431-0180; Braig, Henk/0000-0001-9592-1141; Cameron,
Stephen/0000-0002-6694-4130; Tubio, Jose/0000-0003-3540-2459; Garrett
Vieira, Filipe/0000-0002-8464-7770; Waterhouse,
Robert/0000-0003-4199-9052
NR 68
TC 218
Z9 232
U1 4
U2 79
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 JUL 6
PY 2010
VL 107
IS 27
BP 12168
EP 12173
DI 10.1073/pnas.1003379107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621JI
UT WOS:000279572100025
PM 20566863
ER
PT J
AU Aiba, Y
Kometani, K
Hamadate, M
Moriyama, S
Sakaue-Sawano, A
Tomura, M
Luche, H
Fehling, HJ
Casellas, R
Kanagawa, O
Miyawaki, A
Kurosaki, T
AF Aiba, Yuichi
Kometani, Kohei
Hamadate, Megumi
Moriyama, Saya
Sakaue-Sawano, Asako
Tomura, Michio
Luche, Herve
Fehling, Hans Joerg
Casellas, Rafael
Kanagawa, Osami
Miyawaki, Atsushi
Kurosaki, Tomohiro
TI Preferential localization of IgG memory B cells adjacent to contracted
germinal centers
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE immunoglobulin; immunological memory
ID PRIMARY IMMUNE-RESPONSE; IN-VIVO; MICE; VISUALIZATION; HYPERMUTATION;
EXPRESSION; ANTIBODIES; RECEPTORS; INDUCTION; SELECTION
AB It has long been presumed that after leaving the germinal centers (GCs), memory B cells colonize the marginal zone or join the recirculating pool. Here we demonstrate the preferential localization of nitrophenol-chicken gamma-globulin-induced CD38(+)IgG1(+) memory B cells adjacent to contracted GCs in the spleen. The memory B cells in this region proliferated after secondary immunization, a response that was abolished by depletion of CD4(+) T cells. We also found that these IgG1(+) memory B cells could present antigen on their surface, and that this activity was required for their activation. These results implicate this peri-GC region as an important site for survival and reactivation of memory B cells.
C1 [Aiba, Yuichi; Kometani, Kohei; Hamadate, Megumi; Moriyama, Saya; Kurosaki, Tomohiro] RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Kanagawa 2300045, Japan.
[Moriyama, Saya; Kurosaki, Tomohiro] Osaka Univ, Grad Sch Frontier Biosci, Lab Lymphocyte Differentiat, Suita, Osaka 5650871, Japan.
[Sakaue-Sawano, Asako; Miyawaki, Atsushi] RIKEN Brain Sci Inst, Lab Cell Funct & Dynam, Wako, Saitama 3510198, Japan.
[Tomura, Michio; Kanagawa, Osami] RIKEN Res Ctr Allergy & Immunol, Lab Autoimmune Regulat, Kanagawa 2300045, Japan.
[Luche, Herve; Fehling, Hans Joerg] Univ Clin Ulm, Inst Immunol, D-89081 Ulm, Germany.
[Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kurosaki, Tomohiro] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Lymphocyte Differentiat, Suita, Osaka 5650871, Japan.
RP Kurosaki, T (reprint author), RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Kanagawa 2300045, Japan.
EM kurosaki@rcai.riken.jp
RI Kurosaki, Tomohiro/D-1306-2009; Miyawaki, Atsushi/K-3569-2014;
OI Kurosaki, Tomohiro/0000-0002-6352-304X; Miyawaki,
Atsushi/0000-0002-2329-3235; LUCHE, Herve/0000-0003-4309-8338
FU Ministry of Education, Culture, Sports, Science, and Technology in
Japan; Japan Science and Technology Agency, Core Research of Evolutional
and Technology
FX We thank Dr. K. A. Pape and Dr. M. K. Jenkins (Department of
Microbiology, Center for Immunology, University of Minnesota Medical
School, Minneapolis) for providing us with the E alpha GFP construct,
Dr. T. Okada for discussions, and Dr. P. D. Burrows for critical reading
of our manuscript. This work was supported by grants to Y.A. and T.K.
from the Ministry of Education, Culture, Sports, Science, and Technology
in Japan and by a grant to T.K. from Japan Science and Technology
Agency, Core Research of Evolutional and Technology.
NR 26
TC 46
Z9 47
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 6
PY 2010
VL 107
IS 27
BP 12192
EP 12197
DI 10.1073/pnas.1005443107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621JI
UT WOS:000279572100029
PM 20547847
ER
PT J
AU Hou, X
Kumar, A
Lee, C
Wang, B
Arjunan, P
Dong, LJ
Maminishkis, A
Tang, ZS
Li, Y
Zhang, F
Zhang, SZ
Wardega, P
Chakrabarty, S
Liu, BY
Wu, ZJ
Colosi, P
Fariss, RN
Lennartsson, J
Nussenblatt, R
Gutkind, JS
Cao, YH
Li, XR
AF Hou, Xu
Kumar, Anil
Lee, Chunsik
Wang, Bin
Arjunan, Pachiappan
Dong, Lijin
Maminishkis, Arvydas
Tang, Zhongshu
Li, Yang
Zhang, Fan
Zhang, Shi-Zhuang
Wardega, Piotr
Chakrabarty, Sagarika
Liu, Baoying
Wu, Zhijian
Colosi, Peter
Fariss, Robert N.
Lennartsson, Johan
Nussenblatt, Robert
Gutkind, J. Silvio
Cao, Yihai
Li, Xuri
TI PDGF-CC blockade inhibits pathological angiogenesis by acting on
multiple cellular and molecular targets
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE choroidal neovascularization; glycogen synthase kinase-3 beta; vascular
biology; retinal neovascularization; ocular disease
ID GROWTH-FACTOR-CC; INTRAVITREAL INJECTION; ALPHA-RECEPTOR; VEGF;
FIBROBLASTS; BEVACIZUMAB; CELLS; BETA; ACTIVATION; PATHWAYS
AB The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological function of PDGF-CC and the underlying cellular and molecular mechanisms remain largely unexplored. Here, using different animal models, we report that PDGF-CC inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed both choroidal and retinal neovascularization. Importantly, we revealed that PDGF-CC targeting acted not only on multiple cell types important for pathological angiogenesis, such as vascular mural and endothelial cells, macrophages, choroidal fibroblasts and retinal pigment epithelial cells, but also on the expression of other important angiogenic genes, such as PDGF-BB and PDGF receptors. At a molecular level, we found that PDGF-CC regulated glycogen synthase kinase (GSK)-3 beta phosphorylation and expression both in vitro and in vivo. Activation of GSK3 beta impaired PDGF-CC-induced angiogenesis, and inhibition of GSK3 beta abolished the antiangiogenic effect of PDGF-CC blockade. Thus, we identified PDGF-CC as an important candidate target gene for antiangiogenic therapy, and PDGF-CC inhibition may be of therapeutic value in treating neovascular diseases.
C1 [Hou, Xu; Kumar, Anil; Lee, Chunsik; Arjunan, Pachiappan; Dong, Lijin; Maminishkis, Arvydas; Tang, Zhongshu; Li, Yang; Zhang, Fan; Chakrabarty, Sagarika; Liu, Baoying; Wu, Zhijian; Colosi, Peter; Fariss, Robert N.; Nussenblatt, Robert; Li, Xuri] NEI, NIH, Bethesda, MD 20892 USA.
[Hou, Xu] Fourth Mil Med Univ, Xijing Hosp, Eye Inst Chinese Peoples Liberat Army, Dept Ophthalmol, Xian 710032, Peoples R China.
[Wang, Bin; Zhang, Shi-Zhuang] Weifang Med Univ, Affiliated Hosp, Med Imaging Ctr, Dept Radiol, Weifang 261042, Peoples R China.
[Wardega, Piotr; Lennartsson, Johan] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden.
[Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Cao, Yihai] Karolinska Inst, Dept Microbiol, S-17177 Stockholm, Sweden.
RP Li, XR (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM lixur@nei.nih.gov
RI Gutkind, J. Silvio/A-1053-2009; Kumar, Anil/K-8504-2012
FU American Health Assistance Foundation; National Institutes of Health,
National Eye Institute
FX This research was supported in part by the Macular Degeneration
Research, a program of the American Health Assistance Foundation, and
the Intramural Research Program of the National Institutes of Health,
National Eye Institute.
NR 29
TC 33
Z9 36
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 JUL 6
PY 2010
VL 107
IS 27
BP 12216
EP 12221
DI 10.1073/pnas.1004143107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621JI
UT WOS:000279572100033
PM 20566880
ER
PT J
AU Traynor, BJ
Nalls, M
Lai, SL
Gibbs, RJ
Schymick, JC
Arepalli, S
Hernandez, D
van der Brug, MP
Johnson, JO
Dillman, A
Cookson, M
Moglia, C
Calvo, A
Restagno, G
Mora, G
Chio, A
AF Traynor, Bryan J.
Nalls, Michael
Lai, Shiao-Lin
Gibbs, Raphael J.
Schymick, Jennifer C.
Arepalli, Sampath
Hernandez, Dena
van der Brug, Marcel P.
Johnson, Janel O.
Dillman, Allissa
Cookson, Mark
Moglia, Cristina
Calvo, Andrea
Restagno, Gabriella
Mora, Gabriele
Chio, Adriano
TI Kinesin-associated protein 3 (KIFAP3) has no effect on survival in a
population-based cohort of ALS patients
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE amyotrophic lateral sclerosis; Italian; survival analysis; genome-wide
association study; gene expression quantitative trait loci mapping
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGNOSIS; EXPRESSION
AB It was recently reported that rs1541160 on chromosome 1q24.2 has a marked effect on survival of amyotrophic lateral sclerosis (ALS) patients by influencing KIFAP3 expression. The cohorts used in that study were collected from ALS specialty clinics. We attempted to replicate these findings in a population-based cohort of 504 Italian ALS patients. None of 140 SNPs genotyped within the KIFAP3 locus (including rs1541160) had an effect on survival (log-rank P value for rs1541160 = 0.47) or on gene expression in that region. These data illustrate the complexities associated with analyzing ALS phenotypes for association.
C1 [Traynor, Bryan J.; Lai, Shiao-Lin; Schymick, Jennifer C.; Johnson, Janel O.] NIA, Neuromuscular Dis Res Grp, Bethesda, MD 20892 USA.
[Nalls, Michael; Gibbs, Raphael J.; Arepalli, Sampath; Hernandez, Dena] NIA, Mol Genet Sect, Bethesda, MD 20892 USA.
[van der Brug, Marcel P.; Dillman, Allissa; Cookson, Mark] NIA, Neurogenet Lab, Cell Biol & Gene Express Unit, Bethesda, MD 20892 USA.
[Lai, Shiao-Lin; Gibbs, Raphael J.; Hernandez, Dena] Inst Neurol, Dept Mol Neurosci, London WC1 3BG, England.
[Lai, Shiao-Lin; Gibbs, Raphael J.; Hernandez, Dena] Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1 3BG, England.
[Lai, Shiao-Lin] Chang Gung Univ Hosp, Chiayi, Taiwan.
[Lai, Shiao-Lin] Coll Med, Chiayi, Taiwan.
[van der Brug, Marcel P.] Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA.
[Moglia, Cristina; Calvo, Andrea; Chio, Adriano] Univ Turin, Dept Neurosci, I-10126 Turin, Italy.
[Restagno, Gabriella] Azienda Osped Osped Infantile Regina Margherita S, Dept Clin Pathol, Mol Genet Unit, I-10126 Turin, Italy.
[Mora, Gabriele] Fdn Salvatore Maugeri, I-20138 Milan, Italy.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Grp, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016; Moglia,
Cristina/K-4142-2016;
OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222;
Chio, Adriano/0000-0001-9579-5341
FU Ministero della Salute, Ricerca Sanitaria Finalizzata; Fondazione Vialli
e Mauro for ALS, Torino; Regione Piemonte, Progetti Finalizzati;
National Institutes of Health, National Institute on Aging
[Z01-AG000949-02]; National Institute of Neurological Disorders and
Stroke; Packard Center for ALS Research at Hopkins; ALS Association
FX This work was supported by Ministero della Salute, Ricerca Sanitaria
Finalizzata 2007 (to A. Chio, G. R., and G. M.), Fondazione Vialli e
Mauro for ALS, Torino (to A. Chio and G. M.), and Regione Piemonte,
Progetti Finalizzati (to G. R.), and the Intramural Research Program of
the National Institutes of Health, National Institute on Aging
(Z01-AG000949-02), National Institute of Neurological Disorders and
Stroke, the Packard Center for ALS Research at Hopkins (to B.J.T.), and
the ALS Association (to B.J.T.).
NR 18
TC 19
Z9 19
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 JUL 6
PY 2010
VL 107
IS 27
BP 12335
EP 12338
DI 10.1073/pnas.0914079107
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621JI
UT WOS:000279572100053
PM 20566859
ER
PT J
AU Chen, G
Shriner, D
Zhou, J
Doumatey, A
Huang, HX
Gerry, NP
Herbert, A
Christman, MF
Chen, YX
Dunston, GM
Faruque, MU
Rotimi, CN
Adeyemo, A
AF Chen, Guanjie
Shriner, Daniel
Zhou, Jie
Doumatey, Ayo
Huang, Hanxia
Gerry, Norman P.
Herbert, Alan
Christman, Michael F.
Chen, Yuanxiu
Dunston, Georgia M.
Faruque, Mezbah U.
Rotimi, Charles N.
Adeyemo, Adebowale
TI Development of admixture mapping panels for African Americans from
commercial high-density SNP arrays
SO BMC GENOMICS
LA English
DT Article
ID NUCLEOTIDE-POLYMORPHISM PANEL; DISEASE-GENE DISCOVERY; CANDIDATE LOCUS;
ANCESTRY; RISK; POPULATIONS; MAP; SUSCEPTIBILITY; HYPERTENSION;
ASSOCIATION
AB Background: Admixture mapping is a powerful approach for identifying genetic variants involved in human disease that exploits the unique genomic structure in recently admixed populations. To use existing published panels of ancestry-informative markers (AIMs) for admixture mapping, markers have to be genotyped de novo for each admixed study sample and samples representing the ancestral parental populations. The increased availability of dense marker data on commercial chips has made it feasible to develop panels wherein the markers need not be predetermined.
Results: We developed two panels of AIMs (similar to 2,000 markers each) based on the Affymetrix Genome-Wide Human SNP Array 6.0 for admixture mapping with African American samples. These two AIM panels had good map power that was higher than that of a denser panel of similar to 20,000 random markers as well as other published panels of AIMs. As a test case, we applied the panels in an admixture mapping study of hypertension in African Americans in the Washington, D. C. metropolitan area.
Conclusions: Developing marker panels for admixture mapping from existing genome-wide genotype data offers two major advantages: (1) no de novo genotyping needs to be done, thereby saving costs, and (2) markers can be filtered for various quality measures and replacement markers (to minimize gaps) can be selected at no additional cost. Panels of carefully selected AIMs have two major advantages over panels of random markers: (1) the map power from sparser panels of AIMs is higher than that of similar to 10-fold denser panels of random markers, and (2) clusters can be labeled based on information from the parental populations. With current technology, chip-based genome-wide genotyping is less expensive than genotyping similar to 20,000 random markers. The major advantage of using random markers is the absence of ascertainment effects resulting from the process of selecting markers. The ability to develop marker panels informative for ancestry from SNP chip genotype data provides a fresh opportunity to conduct admixture mapping for disease genes in admixed populations when genome-wide association data exist or are planned.
C1 [Chen, Guanjie; Shriner, Daniel; Zhou, Jie; Doumatey, Ayo; Huang, Hanxia; Rotimi, Charles N.; Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Gerry, Norman P.; Christman, Michael F.] Coriell Inst Med Res, Camden, NJ 08103 USA.
[Herbert, Alan] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
[Chen, Yuanxiu; Dunston, Georgia M.; Faruque, Mezbah U.] Howard Univ, Natl Human Genome Ctr, Washington, DC 20060 USA.
RP Adeyemo, A (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM adeyemoa@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU NIGMS/MBRS/SCORE [S06GM008016-320107, S06GM008016-380111]; National
Center for Research Resources (NCRR), a component of the National
Institutes of Health (NIH) [2M01RR010284]; Center for Research on
Genomics and Global Health (CRGGH); National Human Genome Research
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases; Center for Information Technology; Office of the Director at
the National Institutes of Health [Z01HG200362]
FX The study was supported by grants S06GM008016-320107 to CNR and
S06GM008016-380111 to AA, both from the NIGMS/MBRS/SCORE Program.
Participant enrollment was carried out at the Howard University General
Clinical Research Center (GCRC), supported by grant number 2M01RR010284
from the National Center for Research Resources (NCRR), a component of
the National Institutes of Health (NIH). The contents of this
publication are solely the responsibility of the authors and do not
necessarily represent the official view of NCRR or NIH. Additional
support was provided by the Coriell Institute for Medical Research. This
research was supported by the Intramural Research Program of the Center
for Research on Genomics and Global Health (CRGGH). The CRGGH is
supported by the National Human Genome Research Institute, the National
Institute of Diabetes and Digestive and Kidney Diseases, the Center for
Information Technology, and the Office of the Director at the National
Institutes of Health (Z01HG200362).
NR 41
TC 9
Z9 9
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 5
PY 2010
VL 11
AR 417
DI 10.1186/1471-2164-11-417
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 662CR
UT WOS:000282785000003
PM 20602785
ER
PT J
AU Drazen, JM
de Leeuw, PW
Laine, C
Mulrow, C
DeAngelis, CD
Frizelle, FA
Godlee, F
Haug, C
Hebert, PC
James, A
Kotzin, S
Marusic, A
Reyes, H
Rosenberg, J
Sahni, P
Van der Weyden, MB
Zhaori, G
AF Drazen, Jeffrey M.
de Leeuw, Peter W.
Laine, Christine
Mulrow, Cynthia
DeAngelis, Catherine D.
Frizelle, Frank A.
Godlee, Fiona
Haug, Charlotte
Hebert, Paul C.
James, Astrid
Kotzin, Sheldon
Marusic, Ana
Reyes, Humberto
Rosenberg, Jacob
Sahni, Peush
Van der Weyden, Martin B.
Zhaori, Getu
TI Toward more uniform conflict disclosures: the updated ICMJE Conflict of
Interest Reporting Form
SO CHINESE MEDICAL JOURNAL
LA English
DT Editorial Material
C1 [Mulrow, Cynthia] Amer Coll Physicians, Philadelphia, PA 19106 USA.
[Kotzin, Sheldon] Natl Lib Med, Bethesda, MD 20894 USA.
RP Mulrow, C (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA.
EM cmulrow@mail.acponline.org
RI Marusic, Ana/E-7683-2013
OI Marusic, Ana/0000-0001-6272-0917
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD JUL 5
PY 2010
VL 123
IS 13
BP 1621
EP 1622
DI 10.3760/cma.j.issn.0366-6999.2010.13.001
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 628AC
UT WOS:000280085300001
PM 20819617
ER
PT J
AU Darrah, PA
Hegde, ST
Patel, DT
Lindsay, RWB
Chen, L
Roederer, M
Seder, RA
AF Darrah, Patricia A.
Hegde, Sonia T.
Patel, Dipti T.
Lindsay, Ross W. B.
Chen, Linda
Roederer, Mario
Seder, Robert A.
TI IL-10 production differentially influences the magnitude, quality, and
protective capacity of Th1 responses depending on the vaccine platform
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID LEISHMANIA-MAJOR INFECTION; T-CELL RESPONSES; DENDRITIC CELLS; T(H)1
CELLS; IMMUNITY; ADJUVANTS; RECEPTOR; MICE; INTERLEUKIN-10; EFFICACY
AB The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4(+) T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4(+) T cell production of interferon (IFN) gamma, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-gamma(+) IL-2(+)TNF(+) Th1 cells, a high frequency of IL-10-producing CD4(+) T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4(+) T cells.
C1 [Darrah, Patricia A.; Hegde, Sonia T.; Patel, Dipti T.; Lindsay, Ross W. B.; Chen, Linda; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rseder@mail.nih.gov
OI Hegde, Sonia/0000-0001-6426-0096
FU National Institute of Allergy and Infectious Diseases, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 35
TC 46
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U1 0
U2 2
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 JUL 5
PY 2010
VL 207
IS 7
BP 1421
EP 1433
DI 10.1084/jem.20092532
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 619XX
UT WOS:000279464700008
PM 20530206
ER
PT J
AU Walter, JE
Rucci, F
Patrizi, L
Recher, M
Regenass, S
Paganini, T
Keszei, M
Pessach, I
Lang, PA
Poliani, PL
Giliani, S
Al-Herz, W
Cowan, MJ
Puck, JM
Bleesing, J
Niehues, T
Schuetz, C
Malech, H
DeRavin, SS
Facchetti, F
Gennery, AR
Andersson, E
Kamani, NR
Sekiguchi, J
Alenezi, HM
Chinen, J
Dbaibo, G
ElGhazali, G
Fontana, A
Pasic, S
Detre, C
Terhorst, C
Alt, FW
Notarangelo, LD
AF Walter, Jolan E.
Rucci, Francesca
Patrizi, Laura
Recher, Mike
Regenass, Stephan
Paganini, Tiziana
Keszei, Marton
Pessach, Itai
Lang, Philipp A.
Poliani, Pietro Luigi
Giliani, Silvia
Al-Herz, Waleed
Cowan, Morton J.
Puck, Jennifer M.
Bleesing, Jack
Niehues, Tim
Schuetz, Catharina
Malech, Harry
DeRavin, Suk See
Facchetti, Fabio
Gennery, Andrew R.
Andersson, Emma
Kamani, Naynesh R.
Sekiguchi, JoAnn
Alenezi, Hamid M.
Chinen, Javier
Dbaibo, Ghassan
ElGhazali, Gehad
Fontana, Adriano
Pasic, Srdjan
Detre, Cynthia
Terhorst, Cox
Alt, Frederick W.
Notarangelo, Luigi D.
TI Expansion of immunoglobulin-secreting cells and defects in B cell
tolerance in Rag-dependent immunodeficiency
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; OMENN-SYNDROME; V(D)J RECOMBINATION;
BONE-MARROW; T-CELLS; HOMEOSTATIC PROLIFERATION; LYMPHOCYTE DEVELOPMENT;
POSITIVE SELECTION; ESCAPE TOLERANCE; MURINE MODEL
AB The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro-B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP-keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4(+) T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell-activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations.
C1 [Walter, Jolan E.; Rucci, Francesca; Patrizi, Laura; Recher, Mike; Pessach, Itai; Andersson, Emma; Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Div Immunol, Sch Med, Boston, MA 02115 USA.
[Walter, Jolan E.; Rucci, Francesca; Patrizi, Laura; Recher, Mike; Pessach, Itai; Andersson, Emma; Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Manton Ctr Orphan Dis Res, Sch Med, Boston, MA 02115 USA.
[Keszei, Marton; Detre, Cynthia; Terhorst, Cox] Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Regenass, Stephan; Fontana, Adriano] Univ Zurich Hosp, Div Clin Immunol, CH-8091 Zurich, Switzerland.
[Paganini, Tiziana; Giliani, Silvia] Univ Brescia, Pediat Clin, Nocivelli Inst Mol Med, I-25123 Brescia, Italy.
[Poliani, Pietro Luigi; Facchetti, Fabio] Univ Brescia, Dept Pathol, I-25123 Brescia, Italy.
[Lang, Philipp A.] Univ Toronto, Dept Immunol, Ontario Canc Inst, Campbell Inst Breast Canc Res, Toronto, ON M5G 2M9, Canada.
[Al-Herz, Waleed; Alenezi, Hamid M.] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait 70459, Kuwait.
[Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, Sch Med, San Francisco, CA 94143 USA.
[Cowan, Morton J.; Puck, Jennifer M.] UCSF Childrens Hosp, San Francisco, CA 94143 USA.
[Bleesing, Jack] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA.
[Niehues, Tim] Univ Dusseldorf, Helios Klinikum Krefeld Acad Hosp, Ctr Child Hlth & Adolescence, D-02151 Dusseldorf, Germany.
[Schuetz, Catharina] Univ Hosp Ulm, Dept Pediat & Adolescent Med, D-89070 Ulm, Germany.
[Malech, Harry; DeRavin, Suk See] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
[Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Kamani, Naynesh R.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Sekiguchi, JoAnn] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Chinen, Javier] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA.
[Dbaibo, Ghassan] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut 11072020, Lebanon.
[ElGhazali, Gehad] King Fahad Med City, Fac Med, Dept Immunol, Riyadh 11525, Saudi Arabia.
[Pasic, Srdjan] Mother & Child Hlth Inst Serbia, Dept Pediat Immunol, Belgrade 11070, Serbia.
RP Notarangelo, LD (reprint author), Harvard Univ, Childrens Hosp, Div Immunol, Sch Med, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; luigi.notarangelo@childrens.harvard.edu
RI Facchetti, Fabio/E-7190-2010; Poliani, Pietro Luigi/E-8145-2010; Keszei,
Marton/F-3295-2014; Notarangelo, Luigi/F-9718-2016;
OI Facchetti, Fabio/0000-0003-4975-2388; Poliani, Pietro
Luigi/0000-0002-5662-8978; Keszei, Marton/0000-0002-1158-2179;
Notarangelo, Luigi/0000-0002-8335-0262; Sekiguchi,
JoAnn/0000-0002-7178-4258; Malech, Harry/0000-0001-5874-5775
FU National Institutes of Health [P01 AI076210-01A1, U54AI082973-01,
AI063058]; American Academy of Allergy, Asthma and Immunology, American
Thoracic Society; GlaxoSmithKline; Manton Foundation; Dubai Harvard
Foundation for Medical Research; Jeffrey Model Diagnostic Center for
Primary Immunodeficiencies at Children's Hospital Boston, Fondazione
CARIPLO; University of California; San Francisco Jeffrey Model
Diagnostic Center for Primary Immunodeficiencies; Swiss National Science
Foundation (SNF/SSMBS) [PASMP3-127678/1]
FX This work was partially contributed to by the National Institutes of
Health Grants P01 AI076210-01A1 (to L.D. Notarangelo, F.W. Alt, and C.
Terhorst), U54AI082973-01 (to M.J. Cowan, J.M. Puck, and L.D.
Notarangelo) and AI063058 (to J. Sekiguchi), the 2008 Fellows Career
Development Award by the American Academy of Allergy, Asthma and
Immunology, American Thoracic Society and GlaxoSmithKline (to J.E.
Walter), the Manton Foundation, the Dubai Harvard Foundation for Medical
Research, the Jeffrey Model Diagnostic Center for Primary
Immunodeficiencies at Children's Hospital Boston, Fondazione CARIPLO (to
P.L. Poliani), and the University of California, San Francisco Jeffrey
Model Diagnostic Center for Primary Immunodeficiencies. M. Recher was
supported by grant PASMP3-127678/1 from the Swiss National Science
Foundation (SNF/SSMBS).
NR 77
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U1 0
U2 3
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 JUL 5
PY 2010
VL 207
IS 7
BP 1541
EP 1554
DI 10.1084/jem.20091927
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 619XX
UT WOS:000279464700017
PM 20547827
ER
PT J
AU Mehra, V
Musib, R
Schito, ML
AF Mehra, V.
Musib, R.
Schito, M. L.
TI Towards developing standardized protocols for evaluation of cellular
mucosal immune responses - Recommendations from a DAIDS/NIH workshop,
June 15-16, 2009
SO VACCINE
LA English
DT Editorial Material
DE Mucosal immunity; HIV/SIV; Systems biology
ID YELLOW-FEVER VACCINE; FEMALE GENITAL-TRACT; T-CELLS; INFECTION; HIV;
IMMUNOGENICITY; INFLAMMATION; LYMPHOCYTES; IMMUNOLOGY
AB Although 80% of HIV infections occur through mucosal routes and vaccine strategies need to be designed for inducing protective immune responses at the site of the viral entry, it has proven to be very challenging to measure these responses. A 2-day workshop was convened by Division of AIDS, National Institutes of Health on June 15-16, 2009 to address the challenges encountered in the evaluation of mucosal T cell immune responses. The goal of the workshop was to obtain recommendations/consensus for developing standardized protocols for the assessment of mucosal immunity. This report summarizes the areas of consensus and recommendations that should assist in developing standardized methodologies for the evaluation of mucosal immune responses.
C1 [Mehra, V.] NIAID, Preclin Res & Dev Branch, Vaccine Res Program, Div AIDS,NIH,HHS, Bethesda, MD USA.
[Musib, R.; Schito, M. L.] NIAID, Henry M Jackson Fdn Advancement Mil Med, Vaccine Res Program, Div AIDS,NIH,HHS, Bethesda, MD USA.
RP Schito, ML (reprint author), 6700-B Rockledge Dr,Room 5255, Bethesda, MD 20892 USA.
EM schitom@niaid.nih.gov
FU PHS HHS [HHSN272200800014C]
NR 22
TC 3
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U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 5
PY 2010
VL 28
IS 30
BP 4689
EP 4694
DI 10.1016/j.vaccine.2010.04.092
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 631KO
UT WOS:000280345700002
PM 20470800
ER
PT J
AU Patel, V
Valentin, A
Kulkarni, V
Rosati, M
Bergamaschi, C
Jalah, R
Alicea, C
Minang, JT
Trivett, MT
Ohlen, C
Zhao, J
Robert-Guroff, M
Khan, AS
Draghia-Akli, R
Felber, BK
Pavlakis, GN
AF Patel, Vainav
Valentin, Antonio
Kulkarni, Viraj
Rosati, Margherita
Bergamaschi, Cristina
Jalah, Rashmi
Alicea, Candido
Minang, Jacob T.
Trivett, Matthew T.
Ohlen, Claes
Zhao, Jun
Robert-Guroff, Marjorie
Khan, Amir S.
Draghia-Akli, Ruxandra
Felber, Barbara K.
Pavlakis, George N.
TI Long-lasting humoral and cellular immune responses and mucosal
dissemination after intramuscular DNA immunization
SO VACCINE
LA English
DT Article
DE DNA vaccine; AIDS vaccine; Rhesus macaque; SAL; PBMC; Rectal mucosa;
Humoral immune response; Cellular immune response; IFN-gamma; TNF alpha;
IL-12; Adjuvant; Immunology
ID SIMIAN IMMUNODEFICIENCY VIRUS; PRIME-BOOST IMMUNIZATION; ELECTROPORATION
IN-VIVO; T-LYMPHOCYTE RESPONSES; RHESUS MACAQUES; HIV-1 DNA; PLASMID
DNA; CANDIDATE VACCINE; GENE-TRANSFER; IMMUNOGENICITY EVALUATION
AB Naive Indian rhesus macaques were immunized with a mixture of optimized plasmid DNAs expressing several Sly antigens using in vivo electroporation via the intramuscular route. The animals were monitored for the development of Sly-specific systemic (blood) and mucosal (bronchoalveolar lavage) cellular and humoral immune responses. The immune responses were of great magnitude, broad (Gag, Pol, Nef, Tat and Vif), long-lasting (up to 90 weeks post third vaccination) and were boosted with each subsequent immunization, even after an extended 90-week rest period. The Sly-specific cellular immune responses were consistently more abundant in bronchoalveolar lavage (BAL) than in blood, and were characterized as predominantly effector memory CD4(+) and CDS(+) T cells in BAL and as both central and effector memory T cells in blood. Sly-specific T cells containing Granzyme B were readily detected in both blood and BAL, suggesting the presence of effector cells with cytolytic potential. DNA vaccination also elicited long-lasting systemic and mucosal humoral immune responses, including the induction of Gag-specific IgA. The combination of optimized DNA vectors and improved intramuscular delivery by in vivo electroporation has the potential to elicit both cellular and humoral responses and dissemination to the periphery, and thus to improve DNA immunization efficacy. Published by Elsevier Ltd.
C1 [Jalah, Rashmi; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Patel, Vainav; Valentin, Antonio; Rosati, Margherita; Bergamaschi, Cristina; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Minang, Jacob T.; Trivett, Matthew T.; Ohlen, Claes] NCI, AIDS & Canc Virus Program, SAIC, Frederick, MD 21702 USA.
[Zhao, Jun; Robert-Guroff, Marjorie] NCI, Immune Biol Retroviral Infect Sect, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Khan, Amir S.; Draghia-Akli, Ruxandra] Inovio Biomed Corp, Blue Bell, PA 19422 USA.
RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, POB B,Bldg 535,Room 206, Frederick, MD 21702 USA.
EM felberb@mail.nih.gov; pavlakig@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank D. Weiss, J. Treece, I. Kalisz and their staff at Advanced
BioScience Laboratories, Inc., Kensington, MD, V. Coalter for expert
help, T. Demberg and P. Kozlowski for advice, and T. Jones for editorial
assistance. This work was supported by the Intramural Research Program
of NIH, National Cancer Institute, Center for Cancer Research.
NR 80
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U1 0
U2 3
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 JUL 5
PY 2010
VL 28
IS 30
BP 4827
EP 4836
DI 10.1016/j.vaccine.2010.04.064
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 631KO
UT WOS:000280345700021
PM 20451642
ER
PT J
AU Sanne, I
Orrell, C
Fox, MP
Conradie, F
Ive, P
Zeinecker, J
Cornell, M
Heiberg, C
Ingram, C
Panchia, R
Rassool, M
Gonin, R
Stevens, W
Truter, H
Dehlinger, M
van der Horst, C
McIntyre, J
Wood, R
AF Sanne, Ian
Orrell, Catherine
Fox, Matthew P.
Conradie, Francesca
Ive, Prudence
Zeinecker, Jennifer
Cornell, Morna
Heiberg, Christie
Ingram, Charlotte
Panchia, Ravindre
Rassool, Mohammed
Gonin, Rene
Stevens, Wendy
Truter, Handre
Dehlinger, Marjorie
van der Horst, Charles
McIntyre, James
Wood, Robin
CA CIPRA-SA Study Team
TI Nurse versus doctor management of HIV-infected patients receiving
antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial
SO LANCET
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY-CARE; EXPERIENCE; RESOURCES;
SURVIVAL; AFRICA
AB Background Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients.
Methods This randomised non-inferiority trial was undertaken at two South African primary-care clinics. HIV-positive individuals with a CD4 cell count of less than 350 cells per mu L or WHO stage 3 or 4 disease were randomly assigned to nurse-monitored or doctor-monitored ART care. Patients were randomly assigned by stratified permuted block randomisation, and neither the patients nor those analysing the data were masked to assignment. The primary objective was a composite endpoint of treatment-limiting events, incorporating mortality, viral failure, treatment-limiting toxic effects, and adherence to visit schedule. Analysis was by intention to treat. Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95% CI for the hazard ratio that was less than 1.40. This study is registered with ClinicalTrials.gov, number NCT00255840.
Findings 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care; all participants were analysed. 371 (46%) patients reached an endpoint of treatment failure: 192 (48%) in the nurse group and 179 (44%) in the doctor group. The hazard ratio for composite failure was 1.09 (95% CI 0.89-1.33), which was within the limits for non-inferiority. After a median follow-up of 120 weeks (IQR 60-144), deaths (ten vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and programme losses (70 vs 63) were similar in nurse and doctor groups, respectively.
Interpretation Nurse-monitored ART is non-inferior to doctor-monitored therapy. Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART.
C1 [Sanne, Ian; Conradie, Francesca; Ive, Prudence; Ingram, Charlotte; Panchia, Ravindre; Rassool, Mohammed; Stevens, Wendy; Truter, Handre] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.
[Orrell, Catherine] Univ Cape Town, Desmond Tutu HIV Ctr, IIDMM, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[Fox, Matthew P.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA.
[Gonin, Rene] Westat Corp, Rockville, IN USA.
[Dehlinger, Marjorie] NIAID, Bethesda, MD 20892 USA.
[van der Horst, Charles] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[McIntyre, James] Anova Hlth Inst, Johannesburg, South Africa.
RP Orrell, C (reprint author), Univ Cape Town, Desmond Tutu HIV Ctr, IIDMM, Fac Hlth Sci, Werner Beit Bldg N,Anzio Rd, ZA-7925 Cape Town, South Africa.
EM catherine.orrell@hiv-research.org.za
RI Wood, Robin/G-8509-2011;
OI Fox, Matthew/0000-0001-9887-0634; Orrell, Catherine/0000-0003-1134-7475;
Cornell, Morna/0000-0001-7149-8799
FU National Institutes of Allergy and Infectious Diseases, the National
Institutes of Health [1U19A153217-01]; US Agency for International
Development (USAID) [674-A-00-08-00007-00]; National Institute of
Allergy And Infectious Diseases [K01AI083097, P30-AI50410]; Gauteng and
Western Cape Provincial Health Authorities; CIPRA-SA Study Team;
Endpoint Review Committee
FX Funding for the CIPRA-SA trial was provided by the Division of AIDS
(DAIDS) of the National Institutes of Allergy and Infectious Diseases,
the National Institutes of Health, through grant number 1U19A153217-01.
Funding was also provided by the US Agency for International Development
(USAID) under the terms of agreement 674-A-00-08-00007-00 with Right to
Care (RTC). The project was also supported by Awards K01AI083097 and
P30-AI50410 from the National Institute of Allergy And Infectious
Diseases. We would like to acknowledge the support of the Gauteng and
Western Cape Provincial Health Authorities, the work of the CIPRA-SA
Study Team, the Endpoint Review Committee (Gary Maartens and David
Spencer), and especially the contribution of our patients. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the Division of AIDS, the National
Institute of Allergy and Infectious Diseases, the National Institutes of
Health, USAID, or other parties.
NR 39
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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 JUL 3
PY 2010
VL 376
IS 9734
BP 33
EP 40
DI 10.1016/S0140-6736(10)60894-X
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624SR
UT WOS:000279841600022
PM 20557927
ER
PT J
AU Masson, MJ
Collins, LA
Carpenter, LD
Graf, ML
Ryan, PM
Bourdi, M
Pohl, LR
AF Masson, Mary Jane
Collins, Lindsay A.
Carpenter, Leah D.
Graf, Mary L.
Ryan, Pauline M.
Bourdi, Mohammed
Pohl, Lance R.
TI Pathologic role of stressed-induced glucocorticoids in drug-induced
liver injury in mice
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Drug-induced liver injury; Stress; RU486; Acetaminophen; Halothane
ID CULTURED MOUSE HEPATOCYTES; INDUCED HEPATOTOXICITY; ACETAMINOPHEN
HEPATOTOXICITY; HYPERSENSITIVITY SYNDROME; CONCANAVALIN-A; MURINE MODEL;
HEPATITIS-C; MITOCHONDRIAL; ACTIVATION; MECHANISM
AB We previously reported that acetaminophen (APAP)-induced liver injury (AILI) in mice is associated with a rise in serum levels of the glucocorticoid (GC), corticosterone. In the current study, we provide evidence that endogenous GC play a pathologic role in AILI. Specifically, pretreatment of mice with the GC receptor (GCR) inhibitor, RU486 (mifepristrone), protected normal but not adrenalectomized mice from AILI, while pretreatment with dexamethasone, a synthetic GC, exacerbated AILI. RU486 did not affect the depletion of whole liver reduced GSH or the formation of APAP-protein adducts. It also had no effects on the formation of reactive oxygen species or the depletion of mitochondrial GSH or ATP. While RU486 pretreatment also protected against halothane-induced liver injury, it exacerbated concanavalin A (ConA)- and carbon tetrachloride (CCl(4))-induced liver injury, demonstrating the complexity of GC effects in different types of liver injury. Conclusion: These results suggest that under certain conditions, elevated levels of GC might represent a previously unappreciated risk factor for liver injury caused by APAP and other drugs through the diverse biological processes regulated by GCR. Published by Elsevier Inc.
C1 [Masson, Mary Jane; Collins, Lindsay A.; Carpenter, Leah D.; Graf, Mary L.; Ryan, Pauline M.; Bourdi, Mohammed; Pohl, Lance R.] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Masson, MJ (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, 10 Ctr Dr,Bldg 10,Room 8N110, Bethesda, MD 20892 USA.
EM massonm@nhlbi.nih.gov; lindsay.a.collins@gmail.com; lcarpent@umd.edu;
graft@nhbli.nih.gov; ryanp3@nhlbi.nih.gov; bourdim@nih.gov;
pohll@nih.gov
FU NIH; NHLBI
FX This research was supported by the Intramural Research Program of the
NIH and the NHLBI.
NR 45
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U2 4
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 JUL 2
PY 2010
VL 397
IS 3
BP 453
EP 458
DI 10.1016/j.bbrc.2010.05.126
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 626OF
UT WOS:000279974600015
PM 20510877
ER
PT J
AU Tang, TTT
Badger, JD
Roche, PA
Roche, KW
AF Tang, Tina Tze-Tsang
Badger, John D., II
Roche, Paul A.
Roche, Katherine W.
TI Novel Approach to Probe Subunit-specific Contributions to
N-Methyl-D-aspartate (NMDA) Receptor Trafficking Reveals a Dominant Role
for NR2B in Receptor Recycling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SYNAPTIC PLASTICITY; C-TERMINUS; ENDOCYTOSIS; EXPRESSION; MOLECULES;
SYNAPSES; BINDING
AB N-Methyl-D-aspartate (NMDA) receptors are expressed at excitatory synapses throughout the brain and are essential for neuronal development and synaptic plasticity. Functional NMDA receptors are tetramers, typically composed of NR1 and NR2 subunits (NR2A-D). NR2A and NR2B are expressed in the forebrain and are thought to assemble as diheteromers (NR1/NR2A, NR1/NR2B) and triheteromers (NR1/NR2A/NR2B). NR2A and NR2B contain cytosolic domains that regulate distinct postendocytic sorting events, with NR2A sorting predominantly into the degradation pathway, and NR2B preferentially trafficking through the recycling pathway. However, the interplay between these two subunits remains an open question. We have now developed a novel approach based on the dimeric feature of the alpha- and beta-chains of the human major histocompatibility complex class II molecule. We created chimeras of alpha- and beta-chains with the NR2A and NR2B C termini and evaluated endocytosis of dimers. Like chimeric proteins containing only a single NR2A or NR2B C-terminal domain, major histocompatibility complex class II-NR2A homodimers sort predominantly to late endosomes, whereas NR2B homodimers traffic to recycling endosomes. Interestingly, NR2A/NR2B heterodimers traffic preferentially through the recycling pathway, and NR2B is dominant in regulating dimer trafficking in both heterologous cells and neurons. In addition, the recycling of NR2B-containing NMDARs in wild-type neurons is not significantly different from NR2A(-/-) neurons. These data support a dominant role for NR2B in regulating the trafficking of triheteromeric NMDARs in vivo. Furthermore, our molecular approach allows for the direct and selective evaluation of dimeric assemblies and can be used to define dominant trafficking domains in other multisubunit protein complexes.
C1 [Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Tang, Tina Tze-Tsang] Univ Bristol, Sch Med Sci, Dept Anat, Med Res Council,Ctr Synapt Plast, Bristol BS8 1TD, Avon, England.
RP Roche, KW (reprint author), NINDS, Receptor Biol Sect, NIH, Bldg 35,Rm 2C903, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
OI Roche, Katherine/0000-0001-7282-6539
FU NINDS, National Institutes of Health; NCI, National Institutes of Health
FX This work was supported by the Intramural Research Program of NINDS and
NCI, National Institutes of Health.
NR 20
TC 14
Z9 15
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 JUL 2
PY 2010
VL 285
IS 27
BP 20975
EP 20981
DI 10.1074/jbc.M110.102210
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 616SH
UT WOS:000279228600061
PM 20427279
ER
PT J
AU Plaza, A
Bifulco, G
Masullo, M
Lloyd, JR
Keffer, JL
Colin, PL
Hooper, JNA
Bell, LJ
Bewley, CA
AF Plaza, Alberto
Bifulco, Giuseppe
Masullo, Milena
Lloyd, John R.
Keffer, Jessica L.
Colin, Patrick L.
Hooper, John N. A.
Bell, Lori J.
Bewley, Carole A.
TI Mutremdamide A and Koshikamides C-H, Peptide Inhibitors of HIV-1 Entry
from Different Thennella Species
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID ANTIFUNGAL CYCLIC-PEPTIDES; SPONGE THEONELLA SP; HETERONUCLEAR
COUPLING-CONSTANTS; CYANOBACTERIUM NOSTOC SP; CONSTITUENT AMINO-ACIDS;
MARINE SPONGE; MICROSCLERODERMA SP; RELATIVE CONFIGURATION;
ABSOLUTE-CONFIGURATION; ORGANIC-COMPOUNDS
AB A new sulfated cyclic depsipeptide, termed mutremdamide A, and six new highly N-methylated peptides, termed koshikam ides C-H, were isolated from different deep-water specimens of Theonella swinhoei and Theonella cupola. Their structures were determined using extensive 2D NMR, ESI, or CDESI and QTOF-MS/MS experiments and absolute configurations established by quantum mechanical calculations, advanced Marley's method, and chiral H PLC. Mutremdamide A displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid and a new N(delta)-carbamoyl-beta-sulfated asparagine. Koshikamides C-E are linear undecapeptides, and koshikamides F-H are 17-residue depsipeptides containing a 10-residue macrolactone. Koshikamides F and G differ from B and II in part by the presence of the conjugated unit 2-(3-amino-5-oxopyrrolidin-2-ylidene)propanoic acid. Cyclic koshikamides F and H inhibited HIV-1 entry at low micromolar concentrations while their linear counterparts were inactive. The Theonella collections studied here are distinguished by co-occurrence of mutremdamide A, koshikamides, and theonellamides, the combination of which appears to define a new Theonella chemotype that can be found in deeper waters.
C1 [Plaza, Alberto; Lloyd, John R.; Keffer, Jessica L.; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Bifulco, Giuseppe; Masullo, Milena] Univ Salerno, Dipartimento Sci Farmaceut, I-84084 Salerno, Italy.
[Hooper, John N. A.] Queensland Museum, Brisbane, Qld 4101, Australia.
RP Bewley, CA (reprint author), NIDDKD, 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; Hooper, John/0000-0003-1722-5954;
Keffer, Jessica/0000-0002-0302-3588
FU Intramural AIDS Targeted Antiviral Program; Office of the Director, NIH;
NIH Intramural Research Program (NIDDK)
FX We thank H. Baker for HIV-1 neutralization assays; the AIDS Research and
Reference Reagent Program, Division of AIDS, NIAID, NIH, for reagents
and cell lines used in the HIV-1 neutralization assays; and M. Kelly and
the National Cancer Institute for identification of T. cupola. The
underwater photograph of T. swinhoei was provided by co-author P. L.
Colin, and the cover art was designed by M. Garraffo. This work was
supported by the Intramural AIDS Targeted Antiviral Program, Office of
the Director, NIH (C.A.B.), and the NIH Intramural Research Program
(NIDDK).
NR 34
TC 29
Z9 30
U1 0
U2 19
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 JUL 2
PY 2010
VL 75
IS 13
BP 4344
EP 4355
DI 10.1021/jo100076g
PG 12
WC Chemistry, Organic
SC Chemistry
GA 614BV
UT WOS:000279030900002
PM 20402515
ER
PT J
AU Duncan, B
Nazarov-Stoica, C
Surls, J
Kehl, M
Bona, C
Casares, S
Brumeanu, TD
AF Duncan, Beverly
Nazarov-Stoica, Cristina
Surls, Jacqueline
Kehl, Margaret
Bona, Constantin
Casares, Sofia
Brumeanu, Teodor-D.
TI Double Negative (CD3(+)4(-)8(-)) TCR alpha beta Splenic Cells from Young
NOD Mice Provide Long-Lasting Protection against Type 1 Diabetes
SO PLOS ONE
LA English
DT Article
ID REGULATORY T-CELLS; INVARIANT NKT CELLS; VERSUS-HOST-DISEASE;
GAMMA-DELTA; IN-VIVO; SUPPRESSOR CELLS; INTERFERON-GAMMA; CUTTING EDGE;
ANTIGEN; MOUSE
AB Background: Double negative CD3(+)4(-)8(-) TCR alpha beta splenic cells (DNCD3) can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic beta-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes.
Methodology/Principal Findings: DNCD3 splenic cells from young NOD mice (1) provided long-lasting protection against diabetes transfer in NOD/Scid immunodeficient mice, (2) proliferated and differentiated in the spleen and pancreas of NOD/Scid mice and pre-diabetic NOD mice into IL-10-secreting T-R-1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3(+)(CD4(-)CD8(-))CD28(+)CD69(+)CD25(low) Foxp3(-) iCTLA-4(-)TCR alpha beta(+) with a predominant V beta 13 gene usage.
Conclusions/Significance: These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4(+)CD25(high) Foxp3(+)T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.
C1 [Duncan, Beverly] NCI, NIH, Bethesda, MD 20892 USA.
[Nazarov-Stoica, Cristina; Surls, Jacqueline; Kehl, Margaret; Casares, Sofia; Brumeanu, Teodor-D.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Bona, Constantin] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA.
[Casares, Sofia] USN, Med Res Ctr, Silver Spring, MD USA.
RP Duncan, B (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM tbrumeanu@usuhs.edu
RI e-, a/F-9947-2012
FU National Institutes of Health [DK61927, DK61326, DK077521,
JDRF-12002-1151]
FX This work was supported by grants from the National Institutes of Health
(DK61927 & DK61326) to T.-D.B., and (DK077521 and JDRF-12002-1151) to S.
C. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 74
TC 19
Z9 21
U1 1
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 JUL 2
PY 2010
VL 5
IS 7
AR e11427
DI 10.1371/journal.pone.0011427
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 619YH
UT WOS:000279465700012
PM 20625402
ER
PT J
AU Li, P
Burke, S
Wang, JX
Chen, XF
Ortiz, M
Lee, SC
Lu, D
Campos, L
Goulding, D
Ng, BL
Dougan, G
Huntly, B
Gottgens, B
Jenkins, NA
Copeland, NG
Colucci, F
Liu, PT
AF Li, Peng
Burke, Shannon
Wang, Juexuan
Chen, Xiongfeng
Ortiz, Mariaestela
Lee, Song-Choon
Lu, Dong
Campos, Lia
Goulding, David
Ng, Bee Ling
Dougan, Gordon
Huntly, Brian
Gottgens, Bertie
Jenkins, Nancy A.
Copeland, Neal G.
Colucci, Francesco
Liu, Pentao
TI Reprogramming of T Cells to Natural Killer-Like Cells upon Bcl11b
Deletion
SO SCIENCE
LA English
DT Article
ID H-2-DEFICIENT LYMPHOMA VARIANTS; IN-VITRO; NK CELLS; DIFFERENTIATION;
RECOGNITION; EXPRESSION; SURVIVAL; PATHWAY; VIVO
AB T cells develop in the thymus and are critical for adaptive immunity. Natural killer (NK) lymphocytes constitute an essential component of the innate immune system in tumor surveillance, reproduction, and defense against microbes and viruses. Here, we show that the transcription factor Bcl11b was expressed in all T cell compartments and was indispensable for T lineage development. When Bcl11b was deleted, T cells from all developmental stages acquired NK cell properties and concomitantly lost or decreased T cell-associated gene expression. These induced T-to-natural killer (ITNK) cells, which were morphologically and genetically similar to conventional NK cells, killed tumor cells in vitro, and effectively prevented tumor metastasis in vivo. Therefore, ITNKs may represent a new cell source for cell-based therapies.
C1 [Li, Peng; Burke, Shannon; Wang, Juexuan; Ortiz, Mariaestela; Lee, Song-Choon; Lu, Dong; Campos, Lia; Goulding, David; Ng, Bee Ling; Dougan, Gordon; Liu, Pentao] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Burke, Shannon; Colucci, Francesco] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England.
[Colucci, Francesco] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
[Chen, Xiongfeng] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Huntly, Brian; Gottgens, Bertie] Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cell Biol, Proteos 138673, Singapore.
RP Liu, PT (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
EM pl2@sanger.ac.uk
RI Colucci, Francesco/F-2844-2010; ASTAR, IMCB/E-2320-2012; huntly,
brian/E-6725-2014;
OI Colucci, Francesco/0000-0001-5193-6376; huntly,
brian/0000-0003-0312-161X; Gottgens, Berthold/0000-0001-6302-5705
FU Wellcome Trust; MRC; BBSRC
FX This work is supported by the Wellcome Trust to P. Liu, from MRC and
BBSRC to F. Colucci, and by MRC to B. Huntly. We thank core facilities
at Sanger Institute (RSF and microarray), Babraham Institute and CIMR
for technical support. Microarray data have been submitted to GEO (Gene
Expression Ominibus). Accession number: GSE21016. A patent application
has been filed by the Wellcome Trust for production and application of
ITNKs (U. K. patent application No. 0912287. U. S. Provisional
Application No. 61/225779), and P. L. and P. L. are listed as authors on
this application. A Mouse/Tissue Transfer Agreement is required for the
use of PLBD mice.
NR 26
TC 138
Z9 138
U1 1
U2 25
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 JUL 2
PY 2010
VL 329
IS 5987
BP 85
EP 89
DI 10.1126/science.1188063
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 619BL
UT WOS:000279402700038
PM 20538915
ER
PT J
AU Luchicchi, A
Lecca, S
Carta, S
Pillolla, G
Muntoni, AL
Yasar, S
Goldberg, SR
Pistis, M
AF Luchicchi, Antonio
Lecca, Salvatore
Carta, Stefano
Pillolla, Giuliano
Muntoni, Anna L.
Yasar, Sevil
Goldberg, Steven R.
Pistis, Marco
TI Effects of fatty acid amide hydrolase inhibition on neuronal responses
to nicotine, cocaine and morphine in the nucleus accumbens shell and
ventral tegmental area: involvement of PPAR-alpha nuclear receptors
SO ADDICTION BIOLOGY
LA English
DT Article
DE Cocaine; dopamine neurons; electrophysiology; nicotine; nucleus
accumbens; peroxisome proliferator-activated receptor-alpha
ID BRAIN REWARD PROCESSES; DOPAMINE NEURONS; ENDOCANNABINOID SYSTEM;
CANNABINOID RECEPTOR; ANANDAMIDE HYDROLYSIS; SYNAPTIC PLASTICITY;
KNOCKOUT MICE; ESTER URB597; ACTIVATION; RATS
AB The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N-acylethanolamine (NAE) anandamide and the endogenous non-cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine-induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine-induced drug self-administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine-induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine-, cocaine- or morphine-induced actions in the ShNAc. Experiments involved single-unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1-receptors and alpha-type peroxisome proliferator-activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine-induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.
C1 [Pistis, Marco] Univ Cagliari, Ctr Excellence Neurobiol Addictf, BB Brodie Dept Neurosci, I-09042 Monserrato, CA, Italy.
[Muntoni, Anna L.] Univ Cagliari, CNR, Neurosci Inst Cagliari, I-09124 Cagliari, Italy.
[Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
[Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD USA.
RP Pistis, M (reprint author), Univ Cagliari, Ctr Excellence Neurobiol Addictf, BB Brodie Dept Neurosci, I-09042 Monserrato, CA, Italy.
EM mpistis@unica.it
RI Pistis, Marco/A-3773-2013;
OI Pistis, Marco/0000-0002-4622-3205; Luchicchi,
Antonio/0000-0002-0189-4347; Pillolla, Giuliano/0000-0002-6797-4905
FU Philip Morris USA and Philip Morris International; Division of Geriatric
Medicine and Gerontology of Johns Hopkins University School of Medicine;
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services
FX This study was supported in part by a grant from Philip Morris USA and
Philip Morris International; by the Division of Geriatric Medicine and
Gerontology of Johns Hopkins University School of Medicine; and by the
Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, Department of Health and Human Services.
NR 55
TC 32
Z9 32
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2010
VL 15
IS 3
BP 277
EP 288
DI 10.1111/j.1369-1600.2010.00222.x
PG 12
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 606AX
UT WOS:000278393800004
PM 20477753
ER
PT J
AU Bjork, K
Terasmaa, A
Sun, H
Thorsell, A
Sommer, WH
Heilig, M
AF Bjoerk, Karl
Terasmaa, Anton
Sun, Hui
Thorsell, Annika
Sommer, Wolfgang H.
Heilig, Markus
TI Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum
mediated by opioid receptors
SO ADDICTION BIOLOGY
LA English
DT Article
DE Dopamine; ethanol; opioids; signal transduction; striatum
ID BEHAVIOR; RAT; ALCOHOLISM
AB The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators of such interactions are poorly understood. Here we report that an acute ethanol challenge induces a robust phosphorylation of two key signal transduction kinases, AKT and DARPP-32, in the striatum of mice. Ethanol-induced AKT phosphorylation was blocked by the opioid receptor antagonist naltrexone but unaffected by blockade of dopamine D2 receptors via sulpiride. In contrast, DARPP-32 phosphorylation was abolished by both antagonists. These data suggest that ethanol acts via two distinct but potentially synergistic striatal signaling cascades. One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs.
C1 [Bjoerk, Karl; Terasmaa, Anton; Sun, Hui; Thorsell, Annika; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Sommer, Wolfgang H.] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
RI Terasmaa, Anton/I-3312-2015;
OI Terasmaa, Anton/0000-0002-5139-1764; Heilig, Markus/0000-0003-2706-2482;
Sommer, Wolfgang/0000-0002-5903-6521; Thorsell,
Annika/0000-0003-3535-3845
FU NIAAA
FX This study was supported by intramural funding from NIAAA.
NR 12
TC 17
Z9 17
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2010
VL 15
IS 3
BP 299
EP 303
DI 10.1111/j.1369-1600.2010.00212.x
PG 5
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 606AX
UT WOS:000278393800006
PM 20456289
ER
PT J
AU Orio, L
Wee, S
Newman, AH
Pulvirenti, L
Koob, GF
AF Orio, Laura
Wee, Sunmee
Newman, Amy H.
Pulvirenti, Luigi
Koob, George F.
TI The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037
decrease progressive ratio responding for methamphetamine in rats with
extended-access
SO ADDICTION BIOLOGY
LA English
DT Article
DE D(3) receptor; dependence; dopamine; methamphetamine; partial agonist;
self-administration
ID FUNCTIONALIZED LINKING CHAINS; CONDITIONED PLACE PREFERENCE; HUMAN
COCAINE FATALITIES; ENHANCED BRAIN REWARD; FOOD-SEEKING BEHAVIOR; D-3
RECEPTOR; DRUG-ADDICTION; PSYCHOSTIMULANT ADDICTION; INDUCED
REINSTATEMENT; INCREASED MOTIVATION
AB Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1-10 mg/kg, i.v) and the D3 antagonist PG01037 (8-32 mg/kg, s.c.) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1-hour sessions 3 days/week) or extended access (long access, LgA; 6 hour sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed ('breakpoint') for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg, and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake.
C1 [Orio, Laura; Wee, Sunmee; Pulvirenti, Luigi; Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Newman, Amy H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Orio, L (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, 10550 N Torrey Pines Rd,SP30-2410, La Jolla, CA 92037 USA.
EM lorio@scripps.edu
RI Orio, Laura/F-4827-2016; koob, george/P-8791-2016
OI Orio, Laura/0000-0002-9614-4062;
FU NIDA [DA10072]; NIH; Pearson Center for Alcoholism and Addiction
Research; MICINN; Fulbright Program for postdoctoral Fulbright Award
[FU-2006-0200]
FX This study was supported by NIDA grant DA10072 (G.F.K.),
NIDA.-Intramural Research Program, NIH (A.H.N.) and the Pearson Center
for Alcoholism and Addiction Research. L.O. thanks Spanish MICINN,
F.E.C.Y.T., and Fulbright Program for postdoctoral Fulbright Award
(FU-2006-0200). This is publication number 20493 of the Scripps Research
Institute. First author current address: Laboratorio de Psicobiologia.
Facultad de Psicologia. Universidad Complutense de Madrid; lorio@
psi.ucm.es.
NR 84
TC 25
Z9 25
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2010
VL 15
IS 3
BP 312
EP 323
DI 10.1111/j.1369-1600.2010.00211.x
PG 12
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 606AX
UT WOS:000278393800008
PM 20456290
ER
PT J
AU Diskin, B
Thomas, JL
Nielsen, EJ
Nishikawa, H
White, JA
AF Diskin, Boris
Thomas, James L.
Nielsen, Eric J.
Nishikawa, Hiroaki
White, Jeffery A.
TI Comparison of Node-Centered and Cell-Centered Unstructured Finite-Volume
Discretizations: Viscous Fluxes
SO AIAA JOURNAL
LA English
DT Article; Proceedings Paper
CT 47th AIAA Aerospace Sciences Meeting and Exhibit Including the New
Horizons Forum and Aerospace Exposition
CY JAN 05-08, 2009
CL Orlando, FL
SP AIAA
ID NONUNIFORM MESHES; TURBULENT FLOWS; GRIDS; SCHEMES
AB Finite-volume discretization schemes for viscous fluxes on general grids are compared using node-centered and cell-centered approaches. The grids range from regular grids to highly irregular grids, including random perturbations of the grid nodes. Accuracy and complexity are studied for four nominally second-order accurate schemes: a node-centered scheme and three cell-centered schemes (a node-averaging scheme and two schemes using least-squares face-gradient reconstruction). The two least-squares schemes use either a nearest-neighbor or an adaptive-compact stencil at a face. The node-centered and least-squares schemes have similarly low levels of complexity. The node-averaging scheme has the highest complexity and can fail to converge to the exact solution when clipping of the node-averaged values is used. On highly anisotropic grids, typical of those encountered in grid adaptation, the least-squares schemes, the node-averaging scheme without clipping, and the node-centered scheme demonstrate similar second-order accuracies per degree of freedom. On anisotropic grids over a curved body, typical of turbulent flow simulations, the node-centered scheme is second-order accurate. The node-averaging scheme may degenerate on mixed-element grids. The least-squares schemes have to be amended to maintain second-order accuracy by either introducing a local approximate mapping or modifying the stencil to reflect the direction of strong coupling. Overall, the accuracies of the node-centered and the best cell-centered schemes are comparable at an equivalent number of degrees of freedom on isotropic and curved anisotropic grids. On stretched, randomly perturbed grids in a rectangular geometry, both gradient and discretization errors for all schemes are orders of magnitude higher than corresponding errors on regular grids.
C1 [Diskin, Boris; Nishikawa, Hiroaki] NIA, Hampton, VA 23666 USA.
[Thomas, James L.; Nielsen, Eric J.; White, Jeffery A.] NASA, Langley Res Ctr, Computat AeroSci Branch, Hampton, VA 23681 USA.
RP Diskin, B (reprint author), Univ Virginia, Dept Mech & Aerosp Engn, 100 Explorat Way, Charlottesville, VA 22904 USA.
EM bdiskin@nianet.org; James.L.Thomas@nasa.gov; Eric.J.Nielsen@nasa.gov;
hiro@nianet.org; Jeffery.A.White@nasa.gov
RI Nishikawa, Hiroaki/M-1247-2016
OI Nishikawa, Hiroaki/0000-0003-4472-5313
NR 25
TC 20
Z9 21
U1 0
U2 3
PU AMER INST AERONAUTICS ASTRONAUTICS
PI RESTON
PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA
SN 0001-1452
EI 1533-385X
J9 AIAA J
JI AIAA J.
PD JUL
PY 2010
VL 48
IS 7
BP 1326
EP 1338
DI 10.2514/1.44940
PG 13
WC Engineering, Aerospace
SC Engineering
GA 619GG
UT WOS:000279416600005
ER
PT J
AU Tungsiripat, M
KitchB, D
Glesby, MJ
Gupta, SK
Mellors, JW
Moran, L
Jones, L
Alston-Smith, B
Rooney, JF
Aberg, JA
AF Tungsiripat, Marisa
KitchB, Douglas
Glesby, Marshall J.
Gupta, Samir K.
Mellors, John W.
Moran, Laura
Jones, Lynne
Alston-Smith, Beverly
Rooney, James F.
Aberg, Judith A.
TI A pilot study to determine the impact on dyslipidemia of adding
tenofovir to stable background antiretroviral therapy: ACTG 5206
SO AIDS
LA English
DT Article
ID CLINICAL-TRIALS GROUP; HIV-INFECTED SUBJECTS; RANDOMIZED-TRIAL;
FENOFIBRATE; COMBINATION; EFFICACY; SAFETY; HAART; DF
AB Several studies have reported improvement in lipids after antiretroviral therapy switches to tenofovir disoproxil fumarate (TDF)-containing regimens. We assessed lipid-lowering effects of TDF by adding it to a stable antiretroviral therapy regimen in this double-blind, placebo-controlled crossover study. We demonstrated that nonhigh-density lipoprotein cholesterol, low-density lipoprotein cholestrol, and total cholestrol improved significantly over TDF vs. placebo treatment in HIV-infected individuals with dyslipidemia. Adding TDF to stable, virologically suppressive antiretroviral therapy regimens improved lipid parameters, supporting a lipid-lowering effect of TDF.
C1 [Tungsiripat, Marisa] Cleveland Clin, Cleveland, OH 44195 USA.
[Tungsiripat, Marisa] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[KitchB, Douglas] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Glesby, Marshall J.] Weill Cornell Med Coll, New York, NY USA.
[Gupta, Samir K.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Mellors, John W.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Moran, Laura] ACTG Operat Ctr, Silver Spring, MD USA.
[Jones, Lynne] Frontier Sci & Technol Res Fdn Inc, Amherst, MA USA.
[Alston-Smith, Beverly] NIAID, Bethesda, MD 20892 USA.
[Rooney, James F.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Aberg, Judith A.] NYU, Sch Med, New York, NY USA.
RP Tungsiripat, M (reprint author), Cleveland Clin, G21,9500 Euclid, Cleveland, OH 44195 USA.
EM tungsim@ccf.org
FU National Institute of Allergy and Infectious Diseases [AI38558,
AI068636]; Gilead Sciences; Merck
FX This multicenter trial was conducted by the AIDS Clinical Trials Group
(ACTG) funded by the National Institute of Allergy and Infectious
Diseases (AI38558 and AI068636). Pharmaceutical support provided by
Gilead Sciences, Inc.; M.T.: AI-070078 and AI-069501 to Case Western
Reserve University. D.W.K.: AI-068634 to SDAC/Harvard School of Public
Health. M.J.G.: AI078884 and AI069419 to Weill Cornell Medical College.
S.K.G.: AI-25859 to Indiana University. J.W.M.: AI-069494 to University
of Pittsburgh. J.A.A.: AI-27665, AI069532, and M01RR00096 to New York
University. S.K.G.: Gilead Sciences: Speaker's fees, consultant fees,
and grant support. J.W.M.: Gilead Sciences: Consultant. Merck:
Consultant and grant support. Chimerix: Consultant. RFS Pharmaceuticals:
Owns stock options. J.F.R.: employee of Gilead Sciences. J.A.A.: Gilead
Sciences: Advisory Board, Clinical Trial support, CME sponsored events
Honorarium.
NR 14
TC 29
Z9 29
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 JUL
PY 2010
VL 24
IS 11
BP 1781
EP 1784
DI 10.1097/QAD.0b013e32833ad8b4
PG 4
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 618ZW
UT WOS:000279396600022
PM 20495438
ER
PT J
AU McFarland, W
Abu-Raddad, LJ
Mahfoud, Z
DeJong, J
Riedner, G
Forsyth, A
Khoshnood, K
AF McFarland, Willi
Abu-Raddad, Laith J.
Mahfoud, Ziyad
DeJong, Jocelyn
Riedner, Gabriele
Forsyth, Andrew
Khoshnood, Kaveh
TI HIV/AIDS in the Middle East and North Africa: new study methods,
results, and implications for prevention and care
SO AIDS
LA English
DT Article
ID FEMALE SEX WORKERS; RISK BEHAVIORS; HIV PREVALENCE; DRUG-USERS; EGYPT;
CAIRO
C1 [McFarland, Willi] San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA.
[McFarland, Willi] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Abu-Raddad, Laith J.] Cornell Univ, Qatar Fdn, Weill Cornell Med Coll, Education City, Doha, Qatar.
[Abu-Raddad, Laith J.] Cornell Univ, Weill Cornell Med Coll, Dept Publ Hlth, Ithaca, NY USA.
[Mahfoud, Ziyad; DeJong, Jocelyn] Amer Univ Beirut, Fac Hlth Sci, Beirut, Lebanon.
[Riedner, Gabriele] WHO, Reg Off Eastern Mediterranean, Cairo, Egypt.
[Forsyth, Andrew] NIMH, NIH, Bethesda, MD 20892 USA.
[Khoshnood, Kaveh] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT USA.
RP McFarland, W (reprint author), San Francisco Dept Publ Hlth, 25 Van Ness Ave, San Francisco, CA 94102 USA.
EM Willi_McFarland@hotmail.com
OI Abu-Raddad, Laith/0000-0003-0790-0506
FU Ford Foundation (Cairo Regional Office); EMRO of the WHO; NIMH of the US
NIH
FX This supplement was made possible by the Faculty of Health Sciences of
the AUB through hosting regional workshops to build scientific writing
capacity, donating faculty time and mentorship, and providing scientific
guidance to bring the articles herein to fruition. The authors are also
grateful to the AUB for their gracious hospitality, the serenity
afforded by the use of their campus, and their attentive logistical
support. Funding for the production of this supplement was provided by
the Ford Foundation (Cairo Regional Office), the EMRO of the WHO, and
the NIMH of the US NIH. Individual studies presented within this
supplement were supported by the institutions and organizations
indicated within each article.
NR 13
TC 5
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL
PY 2010
VL 24
SU 2
BP S1
EP S4
DI 10.1097/01.aids.0000386728.49059.92
PG 4
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 622WQ
UT WOS:000279697100001
PM 20610944
ER
PT J
AU Mikovits, JA
Huang, Y
Pfost, MA
Lombardi, VC
Bertolette, DC
Hagen, KS
Ruscetti, FW
AF Mikovits, Judy A.
Huang, Ying
Pfost, Max A.
Lombardi, Vincent C.
Bertolette, Daniel C.
Hagen, Kathryn S.
Ruscetti, Francis W.
TI Distribution of Xenotropic Murine Leukemia Virus-Related Virus (XMRV)
Infection in Chronic Fatigue Syndrome and Prostate Cancer
SO AIDS REVIEWS
LA English
DT Review
DE Biological amplification; Molecular enrichment; XMRV; Chronic fatigue
syndrome; Prostate cancer; New retrovirus
ID DEFINITION; PREVALENCE; RETROVIRUS; CELLS
AB In 2006, sequences described as xenotropic murine leukemia virus-related virus (XMRV) were discovered in prostate cancer patients. In October 2009, we published the first direct isolation of infectious XMRV from humans and the detection of infectious XMRV in patients with chronic fatigue syndrome. In that study, a combination of classic retroviral methods were used including: DNA polymerase chain reaction and reverse transcriptase polymerase chain reaction for gag and env, full length genomic sequencing, immunoblotting for viral protein expression in activated peripheral blood mononuclear cells, passage of infectious virus in both plasma and peripheral blood mononuclear cells to indicator cell lines, and detection of antibodies to XMRV in plasma. A combination of these methods has since allowed us to confirm infection by XMRV in 85% of the 101 patients that were originally studied. Since 2009, seven studies, predominantly using DNA polymerase chain reaction of blood products or tumor tissue, have reported failures to detect XMRV infection in patients with either prostate cancer or chronic fatigue syndrome. A review of the current literature on XMRV supports the importance of applying multiple independent techniques in order to determine the presence of this virus. Detection methods based upon the biological and molecular amplification of XMRV, which is usually present at low levels in unstimulated blood cells and plasma, are more sensitive than assays for the virus by DNA polymerase chain reaction of unstimulated peripheral blood mononuclear cells. When we examined patient blood samples that had originally tested negative by DNA polymerase chain reaction by more sensitive methods, we observed that they were infected with XMRV; thus, the DNA polymerase chain reaction tests provided false negative results. Therefore, we conclude that molecular analyses using DNA from unstimulated peripheral blood mononuclear cells or from whole blood are not yet sufficient as stand-alone assays for the identification of XMRV-infected individuals. Complementary methods are reviewed, that if rigorously followed, will likely show a more accurate snapshot of the actual distribution of XMRV infection in humans. (AIDS Rev. 2010;12:149-52)
C1 [Mikovits, Judy A.] Univ Nevada, Appl Res Facil, Whittemore Peterson Inst, Reno, NV 89557 USA.
[Huang, Ying; Bertolette, Daniel C.; Ruscetti, Francis W.] NCI, Lab Expt Immunol, Canc & Inflammat Program, Frederick, MD 21701 USA.
RP Mikovits, JA (reprint author), Univ Nevada, Appl Res Facil, Whittemore Peterson Inst, Rm 401 MS199,1664 N Virginia St, Reno, NV 89557 USA.
EM judym@wpinstitute.org
NR 25
TC 12
Z9 12
U1 1
U2 3
PU PERMANYER PUBL
PI BARCELONA
PA MALLORCA, 310, BARCELONA, 00000, SPAIN
SN 1139-6121
J9 AIDS REV
JI Aids Rev.
PD JUL-SEP
PY 2010
VL 12
IS 3
BP 149
EP 152
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 651II
UT WOS:000281921000003
PM 20842203
ER
PT J
AU Urv, TK
Zigman, WB
Silverman, W
AF Urv, Tiina K.
Zigman, Warren B.
Silverman, Wayne
TI Psychiatric Symptoms in Adults With Down Syndrome and Alzheimer's
Disease
SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; ADAPTIVE-BEHAVIOR; MENTAL-RETARDATION;
INTELLECTUAL DISABILITY; NEUROPSYCHIATRIC SYMPTOMS; MALADAPTIVE
BEHAVIORS; OLDER-PEOPLE; DEMENTIA; AGE; INDIVIDUALS
AB Changes in psychiatric symptoms related to specific stages of dementia were investigated in 224 adults 45 years of age or older with Down syndrome. Findings indicate that psychiatric symptoms are a prevalent feature of dementia in the population with Down syndrome and that clinical presentation is qualitatively similar to that seen in Alzheimer's disease within the general population. Psychiatric symptoms related to Alzheimer's disease vary by the type of behavior and stage of dementia, but do not seem to be influenced by sex or level of premorbid intellectual impairment. Some psychiatric symptoms may be early indicators of Alzheimer's disease and may appear prior to substantial changes in daily functioning. Improvements in understanding the progression of dementia in individuals with Down syndrome may lead to improved diagnosis and treatment.
C1 [Urv, Tiina K.] NICHHD, Bethesda, MD USA.
[Zigman, Warren B.] New York State Inst Basic Res Dev Disabil, New York, NY USA.
RP Urv, TK (reprint author), NICHD, Bethesda, MD 20892 USA.
EM urvtiin@mail.nih.gov
FU NICHD NIH HHS [P30 HD024061, P01 HD035897]
NR 56
TC 15
Z9 15
U1 1
U2 16
PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES
PI WASHINGTON
PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA
SN 1944-7515
J9 AJIDD-AM J INTELLECT
JI AJIDD-Am. J. Intellect. Dev. Disabil.
PD JUL
PY 2010
VL 115
IS 4
BP 265
EP 276
DI 10.1352/1944-7558-115.4.265
PG 12
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 624VE
UT WOS:000279849100001
PM 20597723
ER
PT J
AU Fessler, MB
Jaramillo, R
Crockett, PW
Zeldin, DC
AF Fessler, M. B.
Jaramillo, R.
Crockett, P. W.
Zeldin, D. C.
TI Relationship of serum cholesterol levels to atopy in the US population
SO ALLERGY
LA English
DT Article
DE atopy; cholesterol; high density lipoprotein; immunoglobulin E; low
density lipoprotein
ID MYOCARDIAL-INFARCTION; HDL CHOLESTEROL; LIPOPROTEINS; ADULTS; LIPIDS;
LDL; APOLIPOPROTEINS; ALLERGY
AB P>Background:
Cholesterol promotes Th2 immunity and allergic inflammation in rodents; whether this occurs in humans is unclear. Reports of both direct and inverse associations between serum cholesterol and atopy in different populations suggest that race and/or other demographic variables may modify these relationships.
Aims of the study:
To determine the relationships between levels of three serum cholesterol measures [total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and non-HDL-C] and atopy in a sample representative of the US population.
Methods:
Cross-sectional study of 6854 participants aged >= 6 years from the 2005-2006 National Health and Nutrition Examination Survey.
Results:
In the overall population, adjusted odds ratios (AORs) per two-standard deviation increase in TC and non-HDL-C for biochemical atopy (defined as >= 1 allergen-specific IgE to 19 allergens) were 1.17 [95% confidence interval (CI), 1.00-1.38] and 1.19 (95% CI, 1.03-1.39), respectively. Interactions by race were noted for the two relationships (interaction P = 0.004 and P = 0.009, respectively) with non-Hispanic Whites (NHWs) having direct relationships [TC: AOR 1.27 (95% CI, 1.03-1.57); non-HDL-C: AOR 1.27 (95% CI, 1.03-1.56)] and non-Hispanic Blacks (NHBs) inverse relationships [TC: AOR 0.77 (95% CI, 0.62-0.95); non-HDL-C: AOR 0.86 (95% CI, 0.69-1.08)]. The adjusted HDL-C-atopy relationship was nonsignificant for NHWs and inverse for NHBs [AOR 0.77 (95% CI, 0.61-0.96)]. Relationships were independent of body mass index and serum C-reactive protein and unmodified by corticosteroid or statin usage. Results were similar using current hay fever/allergy as the atopy outcome.
Conclusions:
There are marked inter-racial differences in the relationship between serum cholesterol and atopy in the US population.
C1 [Fessler, M. B.; Zeldin, D. C.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Jaramillo, R.; Crockett, P. W.] SRA Int, Durham, NC USA.
RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA.
EM fesslerm@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES102005,
Z01 ES025041]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (Z01
ES102005 and Z01 ES025041).
NR 17
TC 10
Z9 10
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD JUL
PY 2010
VL 65
IS 7
BP 859
EP 864
DI 10.1111/j.1398-9995.2009.02287.x
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA 604QP
UT WOS:000278293900006
PM 20015326
ER
PT J
AU Boyce, CK
Hotton, CL
AF Boyce, C. Kevin
Hotton, Carol L.
TI "PROTOTAXITES WAS NOT A TAPHONOMIC ARTIFACT"
SO AMERICAN JOURNAL OF BOTANY
LA English
DT Letter
C1 [Boyce, C. Kevin] Univ Chicago, Dept Geophys Sci, Chicago, IL 60637 USA.
[Hotton, Carol L.] Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20560 USA.
[Hotton, Carol L.] NLM NCBI, NIH, Bethesda, MD USA.
RP Boyce, CK (reprint author), Univ Chicago, Dept Geophys Sci, 5734 S Ellis Ave, Chicago, IL 60637 USA.
NR 4
TC 8
Z9 9
U1 4
U2 11
PU BOTANICAL SOC AMER INC
PI ST LOUIS
PA PO BOX 299, ST LOUIS, MO 63166-0299 USA
SN 0002-9122
J9 AM J BOT
JI Am. J. Bot.
PD JUL
PY 2010
VL 97
IS 7
BP 1073
EP 1073
DI 10.3732/ajb.1000104
PG 1
WC Plant Sciences
SC Plant Sciences
GA 621BM
UT WOS:000279548600001
PM 21616858
ER
PT J
AU Chahal, H
Johnson, C
Tandri, H
Jain, A
Hundley, WG
Barr, RG
Kawut, SM
Lima, JAC
Bluemke, DA
AF Chahal, Harjit
Johnson, Craig
Tandri, Harikrishna
Jain, Aditya
Hundley, W. Gregory
Barr, R. Graham
Kawut, Steven M.
Lima, Joao A. C.
Bluemke, David A.
TI Relation of Cardiovascular Risk Factors to Right Ventricular Structure
and Function as Determined by Magnetic Resonance Imaging (Results from
the Multi-Ethnic Study of Atherosclerosis)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID PULMONARY HEMODYNAMICS; CARDIAC-HYPERTROPHY; CIGARETTE-SMOKING; SYSTOLIC
FUNCTION; GRADIENT-ECHO; HUMAN-HEART; MASS; HYPERTENSION; GENDER; VOLUME
AB The effect of cardiovascular risk factors on the left ventricle is well known but their effect on right ventricle has not been studied using advanced imaging techniques. The purpose of the present study was to determine the relation between the cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images from 4,204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis were analyzed. Multivariate linear regression models were used to study the cross-sectional association between individual RV parameters and risk factors. All RV parameters, except for ejection fraction, decreased with age (p <0.0001). The RV mass was positively associated with systolic blood pressure (+0.4 g, p <0.0001) and high-density lipoprotein cholesterol (+0.2 g, p <0.0001). It was inversely related with diastolic blood pressure (-0.3 g, p <0.0001) and total cholesterol (-0.2 g, p <0.01). The RV end-diastolic volume was positively associated with systolic blood pressure (+1.6 ml, p <0.01) and high-density lipoprotein cholesterol (+1.8 ml, p <0.0001). It was inversely related with diastolic blood pressure (-2.2 ml, p <0.01), total cholesterol (-1.4 ml, p <0.0001), current smoking (-2.7 ml, p <0.05), and diabetes mellitus (-3.1 ml, p <0.01). The RV ejection fraction was positively associated with systolic blood pressure (+1.0%, p <0.0001), high-density lipoprotein cholesterol (+0.4%, p <0.0001) and inversely with diastolic blood pressure (-0.7%, p <0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and high-density lipoprotein cholesterol, are associated with subclinical changes in the RV mass and volume. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:110-116)
C1 [Chahal, Harjit; Jain, Aditya; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Tandri, Harikrishna; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Johnson, Craig] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Hundley, W. Gregory] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27103 USA.
[Barr, R. Graham] Columbia Univ, Dept Med & Epidemiol, Med Ctr, New York, NY USA.
[Kawut, Steven M.] Univ Penn, Dept Med & Epidemiol, Philadelphia, PA 19104 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
EM bluemked@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-95159 through N01-HC-95169, R01 HL086719]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 and R01 HL086719 from the National Heart, Lung, and Blood
Institute, Bethesda, Maryland.
NR 30
TC 34
Z9 34
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2010
VL 106
IS 1
BP 110
EP 116
DI 10.1016/j.amjcard.2010.02.022
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 622JX
UT WOS:000279659700020
PM 20609657
ER
PT J
AU Mercken, EM
de Cabo, R
AF Mercken, Evi M.
de Cabo, Rafael
TI A toast to your health, one drink at a time
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Editorial Material
ID ENDOTHELIAL-CELLS; OXIDATIVE STRESS; RESVERATROL
C1 [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, 51 Bayview Blvd,Suite 100,Room 9C218, Baltimore, MD 21224 USA.
EM decabora@mail.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
NR 10
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL 1
PY 2010
VL 92
IS 1
BP 1
EP 2
DI 10.3945/ajcn.2010.29834
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 612YX
UT WOS:000278943100001
PM 20504971
ER
PT J
AU Shomaker, LB
Tanofsky-Kraff, M
Savastano, DM
Kozlosky, M
Columbo, KM
Wolkoff, LE
Zocca, JM
Brady, SM
Yanovski, SZ
Crocker, MK
Ali, A
Yanovski, JA
AF Shomaker, Lauren B.
Tanofsky-Kraff, Marian
Savastano, David M.
Kozlosky, Merel
Columbo, Kelli M.
Wolkoff, Laura E.
Zocca, Jaclyn M.
Brady, Sheila M.
Yanovski, Susan Z.
Crocker, Melissa K.
Ali, Asem
Yanovski, Jack A.
TI Puberty and observed energy intake: boy, can they eat!
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID BODY-COMPOSITION; AFRICAN-AMERICAN; CHILDREN; GIRLS; WOMEN; EXPENDITURE;
ADOLESCENTS; BULIMIA; PATTERN; GROWTH
AB Background: Anecdotal reports suggest that adolescent males consume large quantities of food to meet the growth demands of pubertal development. However, limited experimental data exist to support this impression.
Objective: The objective was to measure energy intakes of youth at different pubertal stages.
Design: Participants were 204 volunteers (50.5% male) aged 817 y. Pubertal development was categorized by physical examination into prepuberty (males: testes < 4 mL; females: Tanner breast stage 1), early-midpuberty (males: testes = 4-12 mL; females: Tanner breast stages 2-3), or late puberty (males: testes >12 mL; females: Tanner breast stages 4-5). Energy intake was measured as consumption from a 9835-kcal food array during 2 lunchtime meals.
Results: Males consumed more energy than did females across all pubertal stages (P < 0.001). Intake increased with pubertal development (P < 0.001), but the timing and magnitude of change varied by sex (P = 0.02). Males' unadjusted energy intake was greater in late puberty (mean +/- SE: 1955 +/- 70 kcal) than in prepuberty (1287 +/- 90 kcal) or early-midpuberty (1413 6 92 kcal) (P < 0.001). Females' unadjusted energy intake tended to be lower among prepubertal girls (905 +/- 140 kcal) than among females in early-midpuberty (1278 +/- 82 kcal, P = 0.07) or late puberty (1388 +/- 68 kcal, P = 0.01). After adjustment for fat-free mass, fat mass, height, overweight status, race, and meal instruction, the main effect of sex (P < 0.001) remained significant, but the effect of puberty was not significant (P = 0.66).
Conclusions: The observed intake patterns are congruent with known sexual dimorphisms for body composition, peak growth velocity, and pubertal development. Consistent with their higher energy requirements, males can consume significantly larger amounts of food than females, especially during later puberty. This trial was registered at clinicaltrials.gov as NCT00320177. Am J Clin Nutr 2010; 92: 123-9.
C1 [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Savastano, David M.; Columbo, Kelli M.; Wolkoff, Laura E.; Zocca, Jaclyn M.; Brady, Sheila M.; Yanovski, Susan Z.; Crocker, Melissa K.; Ali, Asem; Yanovski, Jack A.] Eunice Kennedy Shriver NICHHD, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Columbo, Kelli M.; Wolkoff, Laura E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Yanovski, Susan Z.] NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, NIH, Hatfield Clin Res Ctr, 9000 Rockville Pike,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU NIH Intramural Research Program [Z01-HD-00641]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD);
National Center on Minority Health and Health Disparities; Office of
Behavioral and Social Sciences Research (JAY); Uniformed Services
University of the Health Sciences [R072IC]; National Institute of
Diabetes and Digestive and Kidney Diseases [1R01DK080906]; NICHD
[1F32HD056762]
FX Supported by NIH Intramural Research Program grant Z01-HD-00641 from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) with supplemental funding from the National Center
on Minority Health and Health Disparities and the Office of Behavioral
and Social Sciences Research (JAY); grant R072IC from the Uniformed
Services University of the Health Sciences and grant 1R01DK080906 from
the National Institute of Diabetes and Digestive and Kidney Diseases
(MT-K); and National Research Service Award 1F32HD056762 from NICHD
(LBS).
NR 33
TC 26
Z9 26
U1 0
U2 8
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL 1
PY 2010
VL 92
IS 1
BP 123
EP 129
DI 10.3945/ajcn.2010.29383
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 612YX
UT WOS:000278943100018
PM 20504975
ER
PT J
AU Caulfield, LE
Putnick, DL
Zavaleta, N
Lazarte, F
Albornoz, C
Chen, P
DiPietro, JA
Bornstein, MH
AF Caulfield, Laura E.
Putnick, Diane L.
Zavaleta, Nelly
Lazarte, Fabiola
Albornoz, Carla
Chen, Ping
DiPietro, Janet A.
Bornstein, Marc H.
TI Maternal gestational zinc supplementation does not influence multiple
aspects of child development at 54 mo of age in Peru
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; FETAL HEART-RATE; PREGNANCY; BEHAVIOR;
STABILITY; STRESS; WOMEN
AB Background: Zinc is necessary for central nervous system development, and maternal zinc status has been associated with developmental differences in offspring.
Objective: The objective was to evaluate differences in cognitive, social, and behavioral function in Peruvian children at 54 mo of age whose mothers participated during pregnancy in a zinc supplementation trial.
Design: We attempted to follow up 205 children from a prenatal zinc supplementation trial and present data on 184 (90%) children-86 whose mothers took 25 mg zinc/d in addition to 60 mg iron and 250 mu g folic acid and 98 whose mothers took iron and folic acid only. Following a standardized protocol, we assessed children's intelligence, language and number skills, representational ability, interpersonal understanding, and adaptive behavior and behavioral adjustment. We also assessed aspects of the mother (eg, age, education, verbal intelligence, stresses, and social support in parenting) and the home environment [HOME (Home Observation for the Measurement of the Environment) inventory].
Results: No differences were observed between any of the tests used to characterize cognitive, social, or behavioral development (P > 0.05). Child sex, parity, or treatment compliance did not modify the effects of supplementation on any outcomes.
Conclusion: The addition of zinc to prenatal supplements did not influence developmental outcomes in Peruvian children when assessed at 4.5 y of age. Am J Clin Nutr 2010; 92: 130-6.
C1 [Caulfield, Laura E.; Chen, Ping] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD 21205 USA.
[DiPietro, Janet A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA.
[Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver NICHHD, NIH, Bethesda, MD USA.
[Zavaleta, Nelly; Lazarte, Fabiola; Albornoz, Carla] Inst Invest Nutr, Lima, Peru.
RP Caulfield, LE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Room W2041,615 N Wolfe St, Baltimore, MD 21205 USA.
EM lcaulfie@jhsph.edu
OI Putnick, Diane/0000-0002-6323-749X
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Nestle Research Foundation; USDA CSREES/NRI
FX Supported by HD 042675. MHB and DLP are employed by the NIH, and their
collaboration was supported by the Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development. The original prenatal supplementation trial was supported
by grants from the Nestle Research Foundation and USDA CSREES/NRI.
NR 39
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U1 1
U2 2
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL 1
PY 2010
VL 92
IS 1
BP 130
EP 136
DI 10.3945/ajcn.2010.29407
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 612YX
UT WOS:000278943100019
PM 20484451
ER
PT J
AU Gallicchio, L
Helzlsouer, KJ
Chow, WH
Freedman, DM
Hankinson, SE
Hartge, P
Hartmuller, V
Harvey, C
Hayes, RB
Horst, RL
Koenig, KL
Kolonel, LN
Laden, F
McCullough, ML
Parisi, D
Purdue, MP
Shu, XO
Snyder, K
Stolzenberg-Solomon, RZ
Tworoger, SS
Varanasi, A
Virtamo, J
Wilkens, LR
Xiang, YB
Yu, K
Zeleniuch-Jacquotte, A
Zheng, W
Abnet, CC
Albanes, D
Bertrand, K
Weinstein, SJ
AF Gallicchio, Lisa
Helzlsouer, Kathy J.
Chow, Wong-Ho
Freedman, D. Michal
Hankinson, Susan E.
Hartge, Patricia
Hartmuller, Virginia
Harvey, Chinonye
Hayes, Richard B.
Horst, Ronald L.
Koenig, Karen L.
Kolonel, Laurence N.
Laden, Francine
McCullough, Marjorie L.
Parisi, Dominick
Purdue, Mark P.
Shu, Xiao-Ou
Snyder, Kirk
Stolzenberg-Solomon, Rachael Z.
Tworoger, Shelley S.
Varanasi, Arti
Virtamo, Jarmo
Wilkens, Lynne R.
Xiang, Yong-Bing
Yu, Kai
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Abnet, Christian C.
Albanes, Demetrius
Bertrand, Kimberly
Weinstein, Stephanie J.
TI Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design
and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer
Cancers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; cohort studies; methods; neoplasms; prospective
studies; vitamin D
ID BASE-LINE CHARACTERISTICS; PROSTATE-CANCER; BREAST-CANCER; SERUM
25-HYDROXYVITAMIN-D; POSTMENOPAUSAL WOMEN; MORTALITY-RATES;
OVARIAN-CANCER; MALE SMOKERS; D DEFICIENCY; US WOMEN
AB The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974-2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50-< 75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations.
C1 [Gallicchio, Lisa; Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD 21202 USA.
[Gallicchio, Lisa; Helzlsouer, Kathy J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Chow, Wong-Ho; Freedman, D. Michal; Hartge, Patricia; Purdue, Mark P.; Stolzenberg-Solomon, Rachael Z.; Yu, Kai; Abnet, Christian C.; Albanes, Demetrius; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hankinson, Susan E.; Laden, Francine; Tworoger, Shelley S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hankinson, Susan E.; Laden, Francine; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA USA.
[Hankinson, Susan E.; Laden, Francine; Bertrand, Kimberly] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hartmuller, Virginia] Sci Consulting Grp Inc, Gaithersburg, MD USA.
[Harvey, Chinonye] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hayes, Richard B.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA.
[Hayes, Richard B.; Koenig, Karen L.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Kolonel, Laurence N.; Wilkens, Lynne R.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Parisi, Dominick; Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Varanasi, Arti] Westat Corp, Rockville, MD USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Gallicchio, L (reprint author), Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, 227 St Paul Pl,6th Floor, Baltimore, MD 21202 USA.
EM lgallic@mdmercy.com
RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Purdue,
Mark/C-9228-2016;
OI Abnet, Christian/0000-0002-3008-7843; Purdue, Mark/0000-0003-1177-3108;
Tworoger, Shelley/0000-0002-6986-7046; Hayes,
Richard/0000-0002-0918-661X; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI
[R01 CA098661, P01 CA055075, P01 CA87969, R01 CA49449, R01 CA082838];
NCI [R37 CA54281, P01 CA33619, R01 CA063464, N01PC35137]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Health Professionals Follow-up Study and the Nurses'
Health Study were supported by the NCI (grants P01 CA055075, P01
CA87969, R01 CA49449, and R01 CA082838). The Multiethnic Cohort Study
was supported by the NCI (grants R37 CA54281, P01 CA33619, R01 CA063464,
and N01PC35137). The Shanghai Men's Health Study was supported by the
NCI (grant R01 CA82729). The Shanghai Women's Health Study was supported
by the NCI (grants R37 CA70867 and N02-CP-11010-66). The Prostate, Lung,
Colorectal and Ovarian Cancer Screening Trial was supported by contracts
from the NCI to the University of Colorado, Denver, Colorado (grant
N01-CN-25514); Georgetown University, Washington, DC (grant
N01-CN25522); the Pacific Health Research Institute, Honolulu, Hawaii
(grant N01-CN-25515); the Henry Ford Health System, Detroit, Michigan
(grant N01-CN-25512); the University of Minnesota, Minneapolis,
Minnesota (grant N01CN- 25513); Washington University, St. Louis,
Missouri (grant NO1-CN-25516); the University of Pittsburgh, Pittsburgh,
Pennsylvania (grant N01-CN-25511); the University of Utah, Salt Lake
City, Utah (grant N01-CN-25524); the Marshfield Clinic Research
Foundation, Marshfield, Wisconsin (grant N01-CN-25518); the University
of Alabama, Birmingham, Alabama (grant NO1-CN-75022); Westat, Inc.,
Rockville, Maryland (grant N01-CN-25476); and the University of
California, Los Angeles, Los Angeles, California (grant NO1-CN-25404).
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was
supported by funding provided by the Intramural Research Program of the
NCI and US Public Health Service contracts (grants N01CN- 45165,
N01-RC-45035, and N01-RC-37004). CLUE was supported by the National
Institute on Aging (grant U01 AG018033) and the NCI (grant R01 CA105069
and K07 CA73790). The participation of CLUE investigators was also
supported by an NCI contract awarded to Mercy Medical Center through the
University of Hawaii (Honolulu, Hawaii). The Cancer Prevention Study II
Nutrition Cohort was supported by the American Cancer Society (Atlanta,
Georgia). The authors thank Dr. Karen Phinney of the National Institute
of Standards and Technology for providing the Vitamin D in Human Serum
(SRM 972) used in this work. This paper is based, at least in part, on
information provided by the Maryland Cancer Registry, Maryland
Department of Health and Mental Hygiene. Dr. Ronald L. Horst is the
president and chief executive officer of Heartland Assays, Inc. (Ames,
Iowa).
NR 52
TC 44
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U1 3
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 JUL 1
PY 2010
VL 172
IS 1
BP 10
EP 20
DI 10.1093/aje/kwq116
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400003
PM 20562188
ER
PT J
AU McCullough, ML
Weinstein, SJ
Freedman, DM
Helzlsouer, K
Flanders, WD
Koenig, K
Kolonel, L
Laden, F
Le Marchand, L
Purdue, M
Snyder, K
Stevens, VL
Stolzenberg-Solomon, R
Virtamo, J
Yang, G
Yu, K
Zheng, W
Albanes, D
Ashby, J
Bertrand, K
Cai, H
Chen, Y
Gallicchio, L
Giovannucci, E
Jacobs, EJ
Hankinson, SE
Hartge, P
Hartmuller, V
Harvey, C
Hayes, RB
Horst, RL
Shu, XO
AF McCullough, Marjorie L.
Weinstein, Stephanie J.
Freedman, D. Michal
Helzlsouer, Kathy
Flanders, W. Dana
Koenig, Karen
Kolonel, Laurence
Laden, Francine
Le Marchand, Loic
Purdue, Mark
Snyder, Kirk
Stevens, Victoria L.
Stolzenberg-Solomon, Rachael
Virtamo, Jarmo
Yang, Gong
Yu, Kai
Zheng, Wei
Albanes, Demetrius
Ashby, Jason
Bertrand, Kimberly
Cai, Hui
Chen, Yu
Gallicchio, Lisa
Giovannucci, Edward
Jacobs, Eric J.
Hankinson, Susan E.
Hartge, Patricia
Hartmuller, Virginia
Harvey, Chinonye
Hayes, Richard B.
Horst, Ronald L.
Shu, Xiao-Ou
TI Correlates of Circulating 25-Hydroxyvitamin D
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE body mass index; cohort studies; diet; dietary supplements; ethnic
groups; exercise; seasons; vitamin D
ID VITAMIN-D STATUS; D INSUFFICIENCY; DIETARY-INTAKE; BODY-FAT; ELDERLY
POPULATION; US POPULATION; UNITED-STATES; D DEFICIENCY; WOMEN;
DETERMINANTS
AB Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.
C1 [McCullough, Marjorie L.; Stevens, Victoria L.; Jacobs, Eric J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Weinstein, Stephanie J.; Freedman, D. Michal; Purdue, Mark; Stolzenberg-Solomon, Rachael; Yu, Kai; Albanes, Demetrius; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Helzlsouer, Kathy; Gallicchio, Lisa] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Helzlsouer, Kathy; Gallicchio, Lisa] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Flanders, W. Dana] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Koenig, Karen; Chen, Yu; Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Koenig, Karen; Chen, Yu; Hayes, Richard B.] NYU, Sch Med, Dept Med, New York, NY USA.
[Koenig, Karen; Chen, Yu; Hayes, Richard B.] NYU, Inst Canc, New York, NY USA.
[Kolonel, Laurence; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Laden, Francine; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Laden, Francine; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Laden, Francine; Bertrand, Kimberly; Giovannucci, Edward; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Snyder, Kirk; Ashby, Jason] Informat Management Serv Inc, Silver Spring, MD USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Yang, Gong; Zheng, Wei; Cai, Hui; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hartmuller, Virginia] Sci Consulting Grp Inc, Gaithersburg, MD USA.
[Harvey, Chinonye] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
RP McCullough, ML (reprint author), Amer Canc Soc, Epidemiol Res Program, 6D,250 Williams St, Atlanta, GA 30303 USA.
EM marji.mccullough@cancer.org
RI Kattelmann, Kendra/E-8225-2013; Albanes, Demetrius/B-9749-2015
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI
[R01 CA098661]; NCI [P01 CA055075, P01 CA87969, R01 CA49449, R01
CA082838, R37 CA54281, P01 CA33619, R01 CA063464, N01PC35137, R01
CA82729, R37 CA70867, N02-CP-11010-66, N01-CN-25514, N01-CN-25522];
Pacific Health Research Institute, Honolulu, Hawaii [N01CN- 25515];
Henry Ford Health System, Detroit, Michigan [N01-CN-25512]; University
of Minnesota, Minneapolis, Minnesota [N01-CN-25513]; Washington
University, St. Louis, Missouri [NO1CN- 25516]; University of
Pittsburgh, Pittsburgh, Pennsylvania [N01-CN-25511]; University of Utah,
Salt Lake City, Utah [N01-CN-25524]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Health Professionals Follow-up Study and the Nurses'
Health Study were supported by the NCI (grants P01 CA055075, P01
CA87969, R01 CA49449, and R01 CA082838). The Multiethnic Cohort Study
was supported by the NCI (grants R37 CA54281, P01 CA33619, R01 CA063464,
and N01PC35137). The Shanghai Men's Health Study was supported by the
NCI (grant R01 CA82729). The Shanghai Women's Health Study was supported
by the NCI (grants R37 CA70867 and N02-CP-11010-66). The Prostate, Lung,
Colorectal, Ovarian Cancer Screening Trial was supported by contracts
from the NCI to the University of Colorado, Denver, Colorado (grant
N01-CN-25514); Georgetown University, Washington, DC (grant
N01-CN-25522); the Pacific Health Research Institute, Honolulu, Hawaii
(grant N01CN- 25515); the Henry Ford Health System, Detroit, Michigan
(grant N01-CN-25512); the University of Minnesota, Minneapolis,
Minnesota (grant N01-CN-25513); Washington University, St. Louis,
Missouri (grant NO1CN- 25516); the University of Pittsburgh, Pittsburgh,
Pennsylvania (grant N01-CN-25511); the University of Utah, Salt Lake
City, Utah (grant N01-CN-25524); the Marshfield Clinic Research
Foundation, Marshfield, Wisconsin (grant N01-CN-25518); the University
of Alabama at Birmingham, Birmingham, Alabama (grant NO1-CN-75022);
Westat, Inc., Rockville, Maryland (grant N01-CN-25476); and the
University of California, Los Angeles, Los Angeles, California (grant
NO1-CN-25404). The Alpha-Tocopherol, Beta-Carotene Cancer Prevention
Study was supported by funding provided by the Intramural Research
Program of the NCI and US Public Health Service contracts (grants
N01-CN-45165, N01-RC-45035, and N01-RC-37004). CLUE was supported by the
National Institute on Aging (grant U01 AG018033) and the NCI (grant R01
CA105069 and K07 CA73790). The participation of CLUE investigators was
also supported by an NCI contract awarded to Mercy Medical Center
through the University of Hawaii (Honolulu, Hawaii). The Cancer
Prevention Study II Nutrition Cohort was supported by the American
Cancer Society (Atlanta, Georgia). The authors thank Dr. Karen Phinney
of the National Institute of Standards and Technology for providing the
Vitamin D in Human Serum (SRM 972) used in this work. This report is
based, at least in part, on information provided by the Maryland Cancer
Registry, Maryland Department of Health and Mental Hygiene. Dr. Ronald
L. Horst is the president and chief executive officer of Heartland
Assays, Inc. (Ames, Iowa).
NR 52
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 21
EP 35
DI 10.1093/aje/kwq113
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400004
PM 20562191
ER
PT J
AU Zeleniuch-Jacquotte, A
Gallicchio, L
Hartmuller, V
Helzlsouer, KJ
McCullough, ML
Setiawan, VW
Shu, XO
Weinstein, SJ
Weiss, JM
Arslan, AA
De Vivo, I
Gao, YT
Hayes, RB
Henderson, BE
Horst, RL
Koenig, KL
Patel, AV
Purdue, MP
Snyder, K
Steplowski, E
Yu, K
Zheng, W
Hankinson, SE
AF Zeleniuch-Jacquotte, Anne
Gallicchio, Lisa
Hartmuller, Virginia
Helzlsouer, Kathy J.
McCullough, Marjorie L.
Setiawan, V. Wendy
Shu, Xiao-Ou
Weinstein, Stephanie J.
Weiss, Jocelyn M.
Arslan, Alan A.
De Vivo, Immaculata
Gao, Yu-Tang
Hayes, Richard B.
Henderson, Brian E.
Horst, Ronald L.
Koenig, Karen L.
Patel, Alpa V.
Purdue, Mark P.
Snyder, Kirk
Steplowski, Emily
Yu, Kai
Zheng, Wei
Hankinson, Susan E.
TI Circulating 25-Hydroxyvitamin D and Risk of Endometrial Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; endometrial neoplasms; prospective studies;
vitamin D
ID VITAMIN-D; BREAST-CANCER; SERUM; POPULATION; WOMEN; EXPRESSION;
MORTALITY; ESTROGENS; COHORT; DIET
AB A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-< 75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the < 25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the >= 100 nmol/L category (P-trend = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was >= 100 nmol/L, and for stratified analyses, >= 75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer.
C1 [Zeleniuch-Jacquotte, Anne; Arslan, Alan A.; Hayes, Richard B.; Koenig, Karen L.] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne; Arslan, Alan A.; Hayes, Richard B.; Koenig, Karen L.] NYU, Sch Med, Inst Canc, New York, NY 10016 USA.
[Gallicchio, Lisa; Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Gallicchio, Lisa; Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hartmuller, Virginia] Sci Consulting Grp Inc, Gaithersburg, MD USA.
[McCullough, Marjorie L.; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Setiawan, V. Wendy; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Weinstein, Stephanie J.; Weiss, Jocelyn M.; Purdue, Mark P.; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Snyder, Kirk; Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA.
[De Vivo, Immaculata; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[De Vivo, Immaculata; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Zeleniuch-Jacquotte, A (reprint author), NYU, Sch Med, Dept Environm Med, 650 1st Ave,Room 539, New York, NY 10016 USA.
EM anne.jacquotte@nyumc.org
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI;
NCI [R01 CA098661, P01 CA055075, P01 CA87969, R01 CA49449, R01 CA082838,
R37 CA54281, P01 CA33619, R01 CA063464, N01PC35137, R37 CA70867,
N02-CP11010- 66, N01-CN-25514]; Georgetown University, Washington, DC
[N01-CN-25522]; Pacific Health Research Institute, Honolulu, Hawaii
[N01-CN-25515]; Henry Ford Health System, Detroit, Michigan [N01CN-
25512]; University of Minnesota, Minneapolis, Minnesota [N01-CN-25513]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland), and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Nurses' Health Study was supported by the NCI (grants P01
CA055075, P01 CA87969, R01 CA49449, and R01 CA082838). The Multiethnic
Cohort Study was supported by the NCI (grants R37 CA54281, P01 CA33619,
R01 CA063464, and N01PC35137). The Shanghai Women's Health Study was
supported by the NCI (grants R37 CA70867 and N02-CP11010- 66). The
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial was
supported by contracts from the NCI to the University of Colorado,
Denver, Colorado (grant N01-CN-25514); Georgetown University,
Washington, DC (grant N01-CN-25522); the Pacific Health Research
Institute, Honolulu, Hawaii (grant N01-CN-25515); the Henry Ford Health
System, Detroit, Michigan (grant N01CN- 25512); the University of
Minnesota, Minneapolis, Minnesota (grant N01-CN-25513); Washington
University, St. Louis, Missouri (grant NO1-CN-25516); the University of
Pittsburgh, Pittsburgh, Pennsylvania (grant N01-CN25511); the University
of Utah, Salt Lake City, Utah (grant N01-CN-25524); the Marshfield
Clinic Research Foundation, Marshfield, Wisconsin (grant N01-CN-25518);
the University of Alabama, Birmingham, Alabama (grant NO1-CN-75022);
Westat, Inc., Rockville, Maryland (grant N01-CN-25476); and the
University of California, Los Angeles, California (grant NO1-CN-25404).
CLUE was supported by the National Institute on Aging (grant U01
AG018033) and the National Cancer Institute (grants R01 CA105069 and K07
CA73790). The participation of CLUE investigators was also supported by
an NCI contract awarded to Mercy Medical Center through the University
of Hawaii (Honolulu, Hawaii). The Cancer Prevention Study II Nutrition
Cohort was supported by the American Cancer Society (Atlanta, Georgia).
The authors thank Dr. Karen Phinney of the National Institute of
Standards and Technology for providing the vitamin D in human serum (SRM
972) used in this work. Members of the VDPP Endometrial Cancer Writing
Committee: Anne Zeleniuch-Jacquotte, Lisa Gallicchio, Virginia
Hartmuller, Kathy J. Helzlsouer, Marjorie L. McCullough, V. Wendy
Setiawan, Xiao-Ou Shu, Stephanie J. Weinstein, Jocelyn M. Weiss, and
Susan E. Hankinson. This report is based at least in part on information
provided by the Maryland Cancer Registry, Maryland Department of Health
and Mental Health. Dr. Ronald L. Horst is the President and Chief
Executive Officer of Heartland Assays, Inc.
NR 39
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 36
EP 46
DI 10.1093/aje/kwq114
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400005
PM 20562189
ER
PT J
AU Gallicchio, L
Moore, LE
Stevens, VL
Ahn, J
Albanes, D
Hartmuller, V
Setiawan, VW
Helzlsouer, KJ
Yang, G
Xiang, YB
Shu, XO
Snyder, K
Weinstein, SJ
Yu, K
Zeleniuch-Jacquotte, A
Zheng, W
Cai, QY
Campbell, DS
Chen, Y
Chow, WH
Horst, RL
Kolonel, LN
McCullough, ML
Purdue, MP
Koenig, KL
AF Gallicchio, Lisa
Moore, Lee E.
Stevens, Victoria L.
Ahn, Jiyoung
Albanes, Demetrius
Hartmuller, Virginia
Setiawan, V. Wendy
Helzlsouer, Kathy J.
Yang, Gong
Xiang, Yong-Bing
Shu, Xiao-Ou
Snyder, Kirk
Weinstein, Stephanie J.
Yu, Kai
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Cai, Qiuyin
Campbell, David S.
Chen, Yu
Chow, Wong-Ho
Horst, Ronald L.
Kolonel, Laurence N.
McCullough, Marjorie L.
Purdue, Mark P.
Koenig, Karen L.
TI Circulating 25-Hydroxyvitamin D and Risk of Kidney Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; cohort studies; kidney neoplasms; prospective
studies; vitamin D
ID RENAL-CELL CARCINOMA; VITAMIN-D STATUS; OCCUPATIONAL SUNLIGHT EXPOSURE;
BREAST-CANCER; ULTRAVIOLET-B; MORTALITY; POPULATION; RADIATION; US
AB Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of >= 75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically.
C1 [Gallicchio, Lisa; Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD 21202 USA.
[Gallicchio, Lisa; Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Stevens, Victoria L.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Moore, Lee E.; Albanes, Demetrius; Weinstein, Stephanie J.; Yu, Kai; Chow, Wong-Ho; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ahn, Jiyoung; Zeleniuch-Jacquotte, Anne; Chen, Yu; Koenig, Karen L.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Ahn, Jiyoung; Zeleniuch-Jacquotte, Anne; Chen, Yu] NYU, Inst Canc, New York, NY USA.
[Hartmuller, Virginia] Sci Consulting Grp Inc, Gaithersburg, MD USA.
[Setiawan, V. Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
[Yang, Gong; Shu, Xiao-Ou; Zheng, Wei; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Snyder, Kirk; Campbell, David S.] Informat Management Serv Inc, Silver Spring, MD USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
RP Gallicchio, L (reprint author), Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, 227 St Paul Pl,6th Floor, Baltimore, MD 21202 USA.
EM lgallic@mdmercy.com
RI Kattelmann, Kendra/E-8225-2013; Albanes, Demetrius/B-9749-2015; Purdue,
Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); NCI [R01
CA098661, R37 CA54281, P01 CA33619, R01 CA063464, N01-PC35137, R01
CA82729, R37 CA70867, N02-CP11010- 66]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Multiethnic Cohort Study was supported by the NCI (grants
R37 CA54281, P01 CA33619, R01 CA063464, and N01-PC35137). The Shanghai
Men's Health Study was supported by the NCI (grant R01 CA82729). The
Shanghai Women's Health Study was supported by the NCI (grants R37
CA70867 and N02-CP11010- 66). The Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial was supported by contracts from the NCI to the
University of Colorado, Denver, Colorado (grant N01-CN-25514);
Georgetown University, Washington, DC (grant N01-CN-25522); the Pacific
Health Research Institute, Honolulu, Hawaii (grant N01-CN-25515); the
Henry Ford Health System, Detroit, Michigan (grant N01CN- 25512); the
University of Minnesota, Minneapolis, Minnesota (grant N01-CN-25513);
Washington University, St. Louis, Missouri (grant NO1-CN-25516); the
University of Pittsburgh, Pittsburgh, Pennsylvania (grant N01-CN25511);
the University of Utah, Salt Lake City, Utah (grant N01-CN-25524); the
Marshfield Clinic Research Foundation, Marshfield, Wisconsin (grant
N01-CN-25518); the University of Alabama, Birmingham, Alabama (grant
NO1-CN-75022); Westat, Inc., Rockville, Maryland (grant N01-CN-25476);
and the University of California, Los Angeles, Los Angeles, California
(grant NO1-CN-25404). The Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study was supported by funding provided by the Intramural
Research Program of the NCI and US Public Health Service contracts
(N01-CN-45165, N01-RC-45035, N01-RC37004). CLUE was supported by the
National Institute on Aging (grant U01 AG018033) and the NCI (grants R01
CA105069, K07 CA73790). The participation of CLUE investigators was also
supported by an NCI contract awarded to Mercy Medical Center through the
University of Hawaii (Honolulu, Hawaii). The Cancer Prevention Study II
Nutrition Cohort was supported by the American Cancer Society (Atlanta,
Georgia).
NR 39
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 47
EP 57
DI 10.1093/aje/kwq115
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400006
PM 20562187
ER
PT J
AU Purdue, MP
Freedman, DM
Gapstur, SM
Helzlsouer, KJ
Laden, F
Lim, U
Maskarinec, G
Rothman, N
Shu, XO
Stevens, VL
Zeleniuch-Jacquotte, A
Albanes, D
Bertrand, K
Weinstein, SJ
Yu, K
Irish, L
Horst, RL
Hoffman-Bolton, J
Giovannucci, EL
Kolonel, LN
Snyder, K
Willett, W
Arslan, AA
Hayes, RB
Zheng, W
Xiang, YB
Hartge, P
AF Purdue, Mark P.
Freedman, D. Michal
Gapstur, Susan M.
Helzlsouer, Kathy J.
Laden, Francine
Lim, Unhee
Maskarinec, Gertraud
Rothman, Nathaniel
Shu, Xiao-Ou
Stevens, Victoria L.
Zeleniuch-Jacquotte, Anne
Albanes, Demetrius
Bertrand, Kimberly
Weinstein, Stephanie J.
Yu, Kai
Irish, Lonn
Horst, Ronald L.
Hoffman-Bolton, Judith
Giovannucci, Edward L.
Kolonel, Laurence N.
Snyder, Kirk
Willett, Walter
Arslan, Alan A.
Hayes, Richard B.
Zheng, Wei
Xiang, Yong-Bing
Hartge, Patricia
TI Circulating 25-Hydroxyvitamin D and Risk of Non-Hodgkin Lymphoma
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE calcifediol; calcitrol; case-control studies; cohort studies;
25-hydroxyvitamin D 2; lymphoma; non-Hodgkin; prospective studies;
vitamin D
ID ULTRAVIOLET-RADIATION EXPOSURE; VITAMIN-D-RECEPTOR; SUN EXPOSURE;
UNITED-STATES; SUNLIGHT; MORTALITY; CANCERS
AB Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects.
C1 [Purdue, Mark P.; Freedman, D. Michal; Rothman, Nathaniel; Albanes, Demetrius; Weinstein, Stephanie J.; Yu, Kai; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Helzlsouer, Kathy J.; Hoffman-Bolton, Judith] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Laden, Francine; Willett, Walter] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Laden, Francine; Bertrand, Kimberly; Giovannucci, Edward L.; Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Lim, Unhee; Maskarinec, Gertraud; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
[Zeleniuch-Jacquotte, Anne; Arslan, Alan A.; Hayes, Richard B.] NYU, Inst Canc, Sch Med, New York, NY USA.
[Irish, Lonn; Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China.
RP Purdue, MP (reprint author), NCI, 6120 Execut Blvd,EPS 8114, Rockville, MD 20852 USA.
EM purduem@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI;
NCI [R01 CA098661, P01 CA055075, P01 CA87969, R01 CA49449, R01 CA082838,
R37 CA54281, P01 CA33619, R01 CA063464, N01PC35137, R01 CA82729, R37
CA70867, N02-CP-11010-66]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Health Professionals Follow-up Study and the Nurses'
Health Study were supported by the NCI (grants P01 CA055075, P01
CA87969, R01 CA49449, and R01 CA082838). The Multiethnic Cohort Study
was supported by the NCI (grants R37 CA54281, P01 CA33619, R01 CA063464,
and N01PC35137). The Shanghai Men's Health Study was supported by the
NCI (grant R01 CA82729). The Shanghai Women's Health Study was supported
by the NCI (grants R37 CA70867 and N02-CP-11010-66). The Prostate, Lung,
Colorectal and Ovarian Cancer Screening Trial was supported by contracts
from the NCI to the University of Colorado, Denver, Colorado (grant
N01-CN-25514); Georgetown University, Washington, DC (grant N01CN-
25522); the Pacific Health Research Institute (grant N01-CN-25515); the
Henry Ford Health System (grant N01-CN-25512); the University of
Minnesota, Minneapolis, Minnesota (grant N01-CN-25513); Washington
University, St. Louis, Missouri (grant NO1-CN-25516); the University of
Pittsburgh, Pittsburgh, Pennsylvania (grant N01-CN25511); the University
of Utah, Salt Lake City, Utah (grant N01-CN-25524); the Marshfield
Clinic Research Foundation, Marshfield, Wisconsin (grant N01-CN25518);
the University of Alabama, Birmingham, Alabama (grant NO1-CN-75022);
Westat, Inc., Rockville, Maryland (grant N01-CN-25476); and the
University of California, Los Angeles, Los Angeles, California (grant
NO1-CN-25404). The Alpha-Tocopherol, Beta-Carotene Cancer Prevention
Study was supported by funding provided by the Intramural Research
Program of the NCI and US Public Health Service contracts (N01-CN-45165,
N01-RC-45035, N01-RC-37004). CLUE was supported by the National
Institute on Aging (grant U01 AG018033) and the NCI (grants R01
CA105069, K07 CA73790). The participation of CLUE investigators was also
supported by an NCI contract awarded toMercy Medical Center through the
University of Hawaii (Honolulu, Hawaii). The Cancer Prevention Study II
Nutrition Cohort was supported by the American Cancer Society (Atlanta,
Georgia).
NR 36
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 58
EP 69
DI 10.1093/aje/kwq117
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400007
PM 20562184
ER
PT J
AU Zheng, W
Danforth, KN
Tworoger, SS
Goodman, MT
Arslan, AA
Patel, AV
McCullough, ML
Weinstein, SJ
Kolonel, LN
Purdue, MP
Shu, XO
Snyder, K
Steplowski, E
Visvanathan, K
Yu, K
Zeleniuch-Jacquotte, A
Gao, YT
Hankinson, SE
Harvey, C
Hayes, RB
Henderson, BE
Horst, RL
Helzlsouer, KJ
AF Zheng, Wei
Danforth, Kim N.
Tworoger, Shelley S.
Goodman, Marc T.
Arslan, Alan A.
Patel, Alpa V.
McCullough, Marjorie L.
Weinstein, Stephanie J.
Kolonel, Laurence N.
Purdue, Mark P.
Shu, Xiao-Ou
Snyder, Kirk
Steplowski, Emily
Visvanathan, Kala
Yu, Kai
Zeleniuch-Jacquotte, Anne
Gao, Yu-Tang
Hankinson, Susan E.
Harvey, Chinonye
Hayes, Richard B.
Henderson, Brian E.
Horst, Ronald L.
Helzlsouer, Kathy J.
TI Circulating 25-Hydroxyvitamin D and Risk of Epithelial Ovarian Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; cohort studies; ovarian neoplasms; prospective
studies; vitamin D
ID VITAMIN-D-RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; DAIRY-PRODUCTS;
MORTALITY-RATES; DOWN-REGULATION; POOLED ANALYSIS; 12 COHORT; GROWTH;
CELLS; WOMEN
AB A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50-< 75 nmol/L, no statistically significant associations were observed for < 37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5-< 50 (OR = 1.03, 95% CI: 0.75, 1.41), or >= 75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of >= 25 kg/m(2) (P-interaction < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women.
C1 [Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Vanderbilt Ingram Canc Ctr,Med Ctr,Sch Med, Nashville, TN 37203 USA.
[Danforth, Kim N.; Weinstein, Stephanie J.; Purdue, Mark P.; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tworoger, Shelley S.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA.
[Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Goodman, Marc T.; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA.
[Patel, Alpa V.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Snyder, Kirk; Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Harvey, Chinonye] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hayes, Richard B.] NYU Med Ctr, New York, NY 10016 USA.
[Henderson, Brian E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Visvanathan, Kala; Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
RP Zheng, W (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Vanderbilt Ingram Canc Ctr,Med Ctr,Sch Med, 2525 W End Ave,8th Floor, Nashville, TN 37203 USA.
EM wei.zheng@vanderbilt.edu
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI;
NCI [R01 CA098661, P01 CA87969, R01 CA49449, P50 CA105009, R37 CA54281,
P01 CA33619, R01 CA063464, N01-PC35137, R37 CA70867, N02-CP-11010-66,
N01-CN25514]; Georgetown University, Washington, DC [N01-CN-25522];
Pacific Health Research Institute, Honolulu, Hawaii [N01-CN-25515];
Henry Ford Health System, Detroit, Michigan [N01-CN-25512]; University
of Minnesota, Minneapolis, Minnesota [N01-CN-25513]; Washington
University, St. Louis, Missouri [NO1-CN-25516]; University of
Pittsburgh, Pittsburgh, Pennsylvania [N01-CN-25511]; University of Utah,
Salt Lake City, Utah [N01-CN25524]; Marshfield Clinic Research
Foundation, Marshfield, Wisconsin [N01-CN-25518]; University of Alabama,
Birmingham, Alabama [NO1-CN-75022]; Westat, Inc., Rockville, Maryland
[N01-CN-25476]; University of California, Los Angeles, California
[NO1-CN-25404]; National Institute on Aging [U01 AG018033]; American
Cancer Society (Atlanta, Georgia)
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland), and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Nurses' Health Study was supported by the NCI (grants P01
CA87969, R01 CA49449, and P50 CA105009). The Multiethnic Co-hort Study
was supported by the NCI (grants R37 CA54281, P01 CA33619, R01 CA063464,
and N01-PC35137). The Shanghai Women's Health Study was supported by the
NCI (grants R37 CA70867 and N02-CP-11010-66). The Prostate, Lung,
Colorectal, and Ovarian Cancer Screening Trial was supported by
contracts from the NCI to the University of Colorado, Denver, Colorado
(grant N01-CN25514); Georgetown University, Washington, DC (grant
N01-CN-25522); the Pacific Health Research Institute, Honolulu, Hawaii
(grant N01-CN-25515); the Henry Ford Health System, Detroit, Michigan
(grant N01-CN-25512); the University of Minnesota, Minneapolis,
Minnesota (grant N01-CN-25513); Washington University, St. Louis,
Missouri (grant NO1-CN-25516); the University of Pittsburgh, Pittsburgh,
Pennsylvania (grant N01-CN-25511); the University of Utah, Salt Lake
City, Utah (grant N01-CN25524); the Marshfield Clinic Research
Foundation, Marshfield, Wisconsin (grant N01-CN-25518); the University
of Alabama, Birmingham, Alabama (grant NO1-CN-75022); Westat, Inc.,
Rockville, Maryland (grant N01-CN-25476); and the University of
California, Los Angeles, California (grant NO1-CN-25404). CLUE was
supported by the National Institute on Aging (grant U01 AG018033) and
the NCI (grants R01 CA105069 and K07 CA73790). The participation of CLUE
was also supported by an NCI contract awarded to Mercy Medical Center
through the University of Hawaii (Honolulu, Hawaii). The Cancer
Prevention Study II Nutrition Cohort was supported by the American
Cancer Society (Atlanta, Georgia).
NR 46
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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
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 70
EP 80
DI 10.1093/aje/kwq118
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400008
PM 20562186
ER
PT J
AU Stolzenberg-Solomon, RZ
Jacobs, EJ
Arslan, AA
Qi, D
Patel, AV
Helzlsouer, KJ
Weinstein, SJ
McCullough, ML
Purdue, MP
Shu, XO
Snyder, K
Virtamo, J
Wilkins, LR
Yu, K
Zeleniuch-Jacquotte, A
Zheng, W
Albanes, D
Cai, QY
Harvey, C
Hayes, R
Clipp, S
Horst, RL
Irish, L
Koenig, K
Le Marchand, L
Kolonel, LN
AF Stolzenberg-Solomon, Rachael Z.
Jacobs, Eric J.
Arslan, Alan A.
Qi, Dai
Patel, Alpa V.
Helzlsouer, Kathy J.
Weinstein, Stephanie J.
McCullough, Marjorie L.
Purdue, Mark P.
Shu, Xiao-Ou
Snyder, Kirk
Virtamo, Jarmo
Wilkins, Lynn R.
Yu, Kai
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Albanes, Demetrius
Cai, Qiuyin
Harvey, Chinonye
Hayes, Richard
Clipp, Sandra
Horst, Ronald L.
Irish, Lonn
Koenig, Karen
Le Marchand, Loic
Kolonel, Laurence N.
TI Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; cohort studies; pancreatic neoplasms; prospective
studies; vitamin D
ID BASE-LINE CHARACTERISTICS; VITAMIN-D STATUS; CELLS IN-VITRO;
BREAST-CANCER; UNITED-STATES; MALE SMOKERS; D ANALOGS; MORTALITY;
INSULIN; PROLIFERATION
AB Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-< 75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (>= 100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.
C1 [Stolzenberg-Solomon, Rachael Z.; Weinstein, Stephanie J.; Purdue, Mark P.; Yu, Kai; Albanes, Demetrius; Hayes, Richard] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Jacobs, Eric J.; Patel, Alpa V.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne; Koenig, Karen] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Qi, Dai; Shu, Xiao-Ou; Zheng, Wei; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
[Helzlsouer, Kathy J.; Clipp, Sandra] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Helzlsouer, Kathy J.; Clipp, Sandra] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Snyder, Kirk; Irish, Lonn] Informat Management Serv Inc, Silver Spring, MD USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Wilkins, Lynn R.; Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Harvey, Chinonye] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
RP Stolzenberg-Solomon, RZ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20852 USA.
EM rs221z@nih.gov
RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI;
NCI [R01 CA098661, R37 CA54281, P01 CA33619, R01 CA063464, N01-PC35137,
R01 CA82729, R37 CA70867, N02-CP11010-66, N01-CN-25514, N01-CN-25522]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Multiethnic Cohort Study was supported by the NCI (grants
R37 CA54281, P01 CA33619, R01 CA063464, and N01-PC35137). The Shanghai
Men's Health Study was supported by the NCI (grant R01 CA82729). The
Shanghai Women's Health Study was supported by the NCI (grants R37
CA70867 and N02-CP11010-66). The Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial was supported by contracts from the NCI to the
University of Colorado, Denver, Colorado (grant N01-CN-25514);
Georgetown University, Washington, DC (grant N01-CN-25522); the Pacific
Health Research Institute, Honolulu, Hawaii (grant N01-CN-25515); the
Henry Ford Health System, Detroit, Michigan (grant N01CN- 25512); the
University of Minnesota, Minneapolis, Minnesota (grant N01-CN-25513);
Washington University, St. Louis, Missouri (grant NO1-CN-25516); the
University of Pittsburgh, Pittsburgh, Pennsylvania (grant N01-CN25511);
the University of Utah, Salt Lake City, Utah (grant N01-CN-25524); the
Marshfield Clinic Research Foundation, Marshfield, Wisconsin (grant
N01-CN-25518); the University of Alabama, Birmingham, Alabama (grant
NO1-CN-75022); Westat, Inc., Rockville, Maryland (grant N01-CN-25476);
and the University of California, Los Angeles, Los Angeles, California
(grant NO1-CN-25404). The Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study was supported by funding provided by the Intramural
Research Program of the NCI and US Public Health Service contracts
(grants N01-CN-45165, N01-RC-45035, and N01RC- 37004). CLUE was
supported by the National Institute on Aging (grant U01 AG018033) and
the NCI (grant R01 CA105069 and K07 CA73790). The participation of CLUE
investigators was also supported by an NCI contract awarded to Mercy
Medical Center through the University of Hawaii (Honolulu, Hawaii). The
Cancer Prevention Study II Nutrition Cohort was supported by the
American Cancer Society (Atlanta, Georgia).
NR 49
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 81
EP 93
DI 10.1093/aje/kwq120
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400009
PM 20562185
ER
PT J
AU Abnet, CC
Chen, Y
Chow, WH
Gao, YT
Helzlsouer, KJ
Le Marchand, L
McCullough, ML
Shikany, JM
Virtamo, J
Weinstein, SJ
Xiang, YB
Yu, K
Zheng, W
Albanes, D
Arslan, AA
Campbell, DS
Campbell, PT
Hayes, RB
Horst, RL
Kolonel, LN
Nomura, AMY
Purdue, MP
Snyder, K
Shu, XO
AF Abnet, Christian C.
Chen, Yu
Chow, Wong-Ho
Gao, Yu-Tang
Helzlsouer, Kathy J.
Le Marchand, Loic
McCullough, Marjorie L.
Shikany, James M.
Virtamo, Jarmo
Weinstein, Stephanie J.
Xiang, Yong-Bing
Yu, Kai
Zheng, Wei
Albanes, Demetrius
Arslan, Alan A.
Campbell, David S.
Campbell, Peter T.
Hayes, Richard B.
Horst, Ronald L.
Kolonel, Laurence N.
Nomura, Abraham M. Y.
Purdue, Mark P.
Snyder, Kirk
Shu, Xiao-Ou
TI Circulating 25-Hydroxyvitamin D and Risk of Esophageal and Gastric
Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; cohort studies; esophageal neoplasms; prospective
studies; stomach neoplasms; vitamin D
ID VITAMIN-D STATUS; MORTALITY; US
AB Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (< 25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-< 75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of < 25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers.
C1 [Abnet, Christian C.; Chow, Wong-Ho; Weinstein, Stephanie J.; Yu, Kai; Albanes, Demetrius; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Chen, Yu; Arslan, Alan A.; Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Chen, Yu] NYU, Sch Med, Dept Med, New York, NY USA.
[Chen, Yu; Arslan, Alan A.; Hayes, Richard B.] NYU, Inst Canc, New York, NY USA.
[McCullough, Marjorie L.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Shikany, James M.] Univ Alabama, Dept Prevent Med, Birmingham, AL USA.
[Le Marchand, Loic; Kolonel, Laurence N.; Nomura, Abraham M. Y.] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
[Campbell, David S.; Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
[Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Suite 320,6120 Execut Blvd, Bethesda, MD 20852 USA.
EM christian.abnet@nih.gov
RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Purdue,
Mark/C-9228-2016
OI Abnet, Christian/0000-0002-3008-7843; Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland); National
Institutes of Health, Division of Cancer Epidemiology and Genetics, NCI;
NCI [R01 CA098661, R37 CA54281, P01 CA33619, R01 CA063464, N01-PC35137,
R01 CA82729, R37 CA70867, N02-CP11010-66, N01-CN-25514, N01-CN-25522,
N01-CN-25513, NO1-CN-25516, N01-CN25511, N01-CN-25524, N01-CN-25518,
NO1-CN-75022, N01-CN-25476]
FX This work was supported by the Extramural Research Program of the
National Institutes of Health, Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI) (Bethesda, Maryland) and the
Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, NCI. The New York
University Women's Health Study was supported by the NCI (grant R01
CA098661). The Multiethnic Cohort Study was supported by the NCI (grants
R37 CA54281, P01 CA33619, R01 CA063464, and N01-PC35137). The Shanghai
Men's Health Study was supported by the NCI (grant R01 CA82729). The
Shanghai Women's Health Study was supported by the NCI (grants R37
CA70867 and N02-CP11010-66). The Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial was supported by contracts from the NCI to the
University of Colorado, Denver, Colorado (grant N01-CN-25514);
Georgetown University, Washington, DC (grant N01-CN-25522); the Pacific
Health Research Institute, Honolulu, Hawaii (grant N01-CN-25515); the
Henry Ford Health System, Detroit, Michigan (grant N01CN-25512); the
University of Minnesota, Minneapolis, Minnesota (grant N01-CN-25513);
Washington University, St. Louis, Missouri (grant NO1-CN-25516); the
University of Pittsburgh, Pittsburgh, Pennsylvania (grant N01-CN25511);
the University of Utah, Salt Lake City, Utah (grant N01-CN-25524); the
Marshfield Clinic Research Foundation, Marshfield, Wisconsin (grant
N01-CN-25518); the University of Alabama, Birmingham, Alabama (grant
NO1-CN-75022); Westat, Inc., Rockville, Maryland (grant N01-CN-25476);
and the University of California, Los Angeles, Los Angeles, California
(grant NO1-CN-25404). The Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study was supported by funding provided by the Intramural
Research Program of the NCI and US Public Health Service contracts
(N01-CN-45165, N01-RC-45035, N01-RC37004). CLUE was supported by the
National Institute on Aging (grant U01 AG018033) and the NCI (grants R01
CA105069, K07 CA73790). The participation of CLUE investigators was also
supported by an NCI contract awarded to Mercy Medical Center through the
University of Hawaii (Honolulu, Hawaii). The Cancer Prevention Study II
Nutrition Cohort was supported by the American Cancer Society (Atlanta,
Georgia).
NR 20
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2010
VL 172
IS 1
BP 94
EP 106
DI 10.1093/aje/kwq121
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 616BS
UT WOS:000279183400010
PM 20562192
ER
PT J
AU Fong, TL
Klontz, KC
Canas-Coto, A
Casper, SJ
Durazo, FA
Davern, TJ
Hayashi, P
Lee, WM
Seeff, LB
AF Fong, Tse-Ling
Klontz, Karl C.
Canas-Coto, Alejandro
Casper, Steven J.
Durazo, Francisco A.
Davern, Timothy J., II
Hayashi, Paul
Lee, William M.
Seeff, Leonard B.
TI Hepatotoxicity Due to Hydroxycut: A Case Series
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID WEIGHT-LOSS SUPPLEMENTS; GREEN TEA; LIVER-INJURY; AUTOIMMUNE-HEPATITIS;
CAUSALITY ASSESSMENT
AB OBJECTIVES: Muscletech Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada) was a popular weight-loss supplement that was recalled by the manufacturer in May 2009 on the basis of reports of hepatotoxicity associated with this supplement. We sought to characterize the clinical presentation of Hydroxycut-associated liver injury and to adjudicate these cases for causal association with Hydroxycut.
METHODS: We assessed the causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study.
RESULTS: Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized, and three of eight patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed eight cases as definite, five highly likely, two probable, and two were considered to be possible.
CONCLUSIONS: Hydroxycut has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight-loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.
C1 [Fong, Tse-Ling] Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, Los Angeles, CA 90033 USA.
[Klontz, Karl C.; Casper, Steven J.] US FDA, Ctr Food Safety & Appl Nutr, Bethesda, MD 20014 USA.
[Canas-Coto, Alejandro; Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Durazo, Francisco A.] Univ Calif Los Angeles, Div Digest & Liver Dis, Los Angeles, CA USA.
[Davern, Timothy J., II] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Hayashi, Paul] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Seeff, Leonard B.] NIH, Liver Dis Res Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
[Durazo, Francisco A.; Davern, Timothy J., II; Lee, William M.] NIDDK, Bethesda, MD 20892 USA.
RP Fong, TL (reprint author), Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, 1510 San Pablo St ,2-F, Los Angeles, CA 90033 USA.
EM tselingf@usc.edu
FU NIDDK NIH HHS [U01 DK065238, U01 DK065184, U01 DK065176, U01 DK083027,
U01 DK065201, U01 DK065211, U01 DK083023, U01 DK082992, U01 DK083020]
NR 29
TC 47
Z9 47
U1 3
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUL
PY 2010
VL 105
IS 7
BP 1561
EP 1566
DI 10.1038/ajg.2010.5
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 620ZD
UT WOS:000279541200015
PM 20104221
ER
PT J
AU Lampl, M
Gotsch, F
Kusanovic, JP
Gomez, R
Nien, JK
Frongillo, EA
Romero, R
AF Lampl, Michelle
Gotsch, Francesca
Kusanovic, Juan Pedro
Gomez, Ricardo
Kae Nien, Jyh
Frongillo, Edward A.
Romero, Roberto
TI Sex Differences in Fetal Growth Responses to Maternal Height and Weight
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Article
ID LOW-BIRTH-WEIGHT; GESTATIONAL-AGE; INTRAUTERINE GROWTH; PROSPECTIVE
COHORT; MALE PREDOMINANCE; PLACENTAL VOLUME; RISK-FACTORS; PREGNANCY;
GENDER; GAIN
AB Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3,495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n = 1,814 males, n = 1,681 females) with birth gestational age, maternal parity, and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth before 18 gestational weeks of age (P = 0.006), and prepregnancy maternal weight and body mass index subsequently had influence (P < 0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (P = 0.003) and more responsive to maternal height among lighter mothers (P <= 0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 g occurred among neonates of the shortest and lightest mothers (P = 0.08), compared to 150 and 191 g among short and heavy mothers, and tall and light-weight mothers, respectively (P = 0.01). Sex differences in response to maternal size are under-appreciated sources of variation in fetal growth studies and may reflect differential growth strategies. Am. J. Hum. Biol. 22:431-443, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Lampl, Michelle] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA.
[Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Lampl, Michelle] Emory Univ, Predict Hlth Ctr Hlth Discover, Atlanta, GA 30322 USA.
[Kusanovic, Juan Pedro] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA.
[Gomez, Ricardo; Kae Nien, Jyh] Pontificia Univ Catolica Chile, Sotero del Rio Hosp, Ctr Perinatal Diag & Res, Puente Alto, Chile.
[Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
RP Lampl, M (reprint author), Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA.
EM mlampl@emory.edu
RI Lampl, Michelle/B-1619-2013
FU Perinatology Research Branch; Division of Intramural Research; Eunice
Kennedy Shriven; National Institute of Child Health and Human
Development; NIH; DHHS
FX Contract grant sponsors: Perinatology Research Branch; Division of
Intramural Research; Eunice Kennedy Shriven; National Institute of Child
Health and Human Development; NIH; DHHS.
NR 76
TC 29
Z9 31
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1042-0533
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD JUL-AUG
PY 2010
VL 22
IS 4
BP 431
EP 443
DI 10.1002/ajhb.21014
PG 13
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA 612DZ
UT WOS:000278878300001
PM 19950190
ER
PT J
AU Tejero, ME
Voruganti, VS
Cai, GW
Cole, SA
Laston, S
Wenger, CR
Mac Cluer, JW
Dyke, B
Devereux, R
Ebbesson, SO
Fabsitz, RR
Howard, BV
Comuzzie, AG
AF Elizabeth Tejero, M.
Voruganti, V. S.
Cai, Guowen
Cole, Shelley A.
Laston, Sandra
Wenger, Charlotte R.
Mac Cluer, Jean W.
Dyke, Bennet
Devereux, Richard
Ebbesson, Sven O.
Fabsitz, Richard R.
Howard, B. V.
Comuzzie, A. G.
TI Pleiotropic Effects on Subclasses of HDL, Adiposity, and Glucose
Metabolism in Adult Alaskan Eskimos
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; HEART-DISEASE;
RISK-FACTORS; LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE;
GENETIC-DETERMINANTS; INSULIN-RESISTANCE; BIVARIATE LINKAGE; OBESITY
AB The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 +/- 0.11 for LDL(2) (intermediate) and 0.89 +/- 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation. Am. J. Hum. Biol. 22:444-448, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Elizabeth Tejero, M.] INMEGEN, Lab Genom Enfermedades Metab Cardiovasc & Nutr, Mexico City 01900, DF, Mexico.
[Elizabeth Tejero, M.; Voruganti, V. S.; Cai, Guowen; Cole, Shelley A.; Laston, Sandra; Wenger, Charlotte R.; Mac Cluer, Jean W.; Dyke, Bennet; Comuzzie, A. G.] SW Fdn Biomed Res, San Antonio, TX 78284 USA.
[Devereux, Richard; Ebbesson, Sven O.] Norton Sound Hlth Corp, Nome, AK USA.
[Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA.
[Howard, B. V.] MedStar Res Inst, Hyattsville, MD USA.
RP Tejero, ME (reprint author), INMEGEN, Lab Genom Enfermedades Metab Cardiovasc & Nutr, Perifer 4124,Torre Zafiro 2,6To Piso, Mexico City 01900, DF, Mexico.
EM etejero@inmegen.gob.mx
FU NIH [RR13556]; [HL082458]; [HL064244]; [MH059490]; [M10RR0047-34]
FX Contract grant numbers: HL082458, HL064244, MH059490, and M10RR0047-34;
Contract Grant sponsor: NIH U01HLO49 Research Facilities Improvement
Program; Contract grant number: RR13556
NR 39
TC 4
Z9 4
U1 0
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1042-0533
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD JUL-AUG
PY 2010
VL 22
IS 4
BP 444
EP 448
DI 10.1002/ajhb.21015
PG 5
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA 612DZ
UT WOS:000278878300002
PM 19950191
ER
PT J
AU Elias, PM
Menon, G
Wetzel, BK
Williams, JW
AF Elias, Peter M.
Menon, Gopinathan
Wetzel, Bruce K.
Williams, John (Jack) W.
TI Barrier Requirements as the Evolutionary "Driver" of Epidermal
Pigmentation in Humans
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Article
ID HUMAN-SKIN COLOR; SINGLE NUCLEOTIDE POLYMORPHISMS;
MELANOCYTE-STIMULATING HORMONE; FIBROBLAST-GROWTH-FACTOR; UVB-INDUCED
ALTERATIONS; PERMEABILITY BARRIER; ULTRAVIOLET-RADIATION; VITAMIN-D;
ATOPIC-DERMATITIS; KIT-LIGAND
AB Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have "driven" the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [approximate to 1.5-0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed approximate to 1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor double right arrow KIT; FOXn1 double right arrow FGF2; IL-1 alpha, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. Am. J. Hum. Biol. 22:526-537,2010. (C)2010 Wiley-Liss, Inc.
C1 [Elias, Peter M.] VA Med Ctr, Dermatol Serv, San Francisco, CA 94121 USA.
[Elias, Peter M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Menon, Gopinathan] Calif Acad Sci, Dept Ornithol & Mammal, San Francisco, CA 94118 USA.
[Wetzel, Bruce K.] Natl Inst Gen Med Sci, Baltimore, MD USA.
[Williams, John (Jack) W.] Univ Wisconsin, Dept Geog, Madison, WI 53706 USA.
RP Elias, PM (reprint author), VA Med Ctr, Dermatol Serv 190, 4150 Clement St, San Francisco, CA 94121 USA.
EM eliasp@derm.ucsf.edu
FU NIH [AR019098, AI059311]; Medical Research Service, Department of
Veterans Affairs, San Francisco, CA
FX Contract grant sponsor: NIH, Contract grant numbers: AR019098, AI059311;
Contract grant sponsor: Medical Research Service, Department of Veterans
Affairs, San Francisco, CA.
NR 119
TC 20
Z9 21
U1 2
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1042-0533
EI 1520-6300
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD JUL-AUG
PY 2010
VL 22
IS 4
BP 526
EP 537
DI 10.1002/ajhb.21043
PG 12
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA 612DZ
UT WOS:000278878300014
PM 20209486
ER
PT J
AU Calof, AL
Kawauchi, S
Santos, R
Lopez-Burks, ME
Hoang, MP
Kitzes, LM
Lao, T
Lechner, MS
Hallgrimsson, B
Daniel, JA
Nussenzweig, A
Lander, AD
AF Calof, Anne L.
Kawauchi, Shimako
Santos, Rosaysela
Lopez-Burks, Martha E.
Hoang, Michelle P.
Kitzes, Leonard M.
Lao, Taotao
Lechner, Mark S.
Hallgrimsson, Benedikt
Daniel, Jeremy A.
Nussenzweig, Andre
Lander, Arthur D.
TI Insights Into Cornelia de Lange Syndrome From the Nipbl-Mutant Mouse
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Meeting Abstract
CT 11th International Congress on Cleft Lip and Palate and Related
Craniofacial Anomalies
CY SEP 10-13, 2009
CL Fortaleza, BRAZIL
C1 [Calof, Anne L.; Kawauchi, Shimako; Santos, Rosaysela; Kitzes, Leonard M.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA.
[Calof, Anne L.; Kawauchi, Shimako; Lopez-Burks, Martha E.; Hoang, Michelle P.; Lander, Arthur D.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
[Calof, Anne L.; Kawauchi, Shimako; Santos, Rosaysela; Lopez-Burks, Martha E.; Hoang, Michelle P.; Lander, Arthur D.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA.
[Calof, Anne L.; Kawauchi, Shimako; Santos, Rosaysela; Kitzes, Leonard M.] Univ Calif Irvine, Ctr Hearing Res, Irvine, CA 92717 USA.
[Calof, Anne L.; Lander, Arthur D.] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92717 USA.
[Lao, Taotao; Lechner, Mark S.] Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA.
[Hallgrimsson, Benedikt] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada.
[Daniel, Jeremy A.; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RI Calof, Anne/A-8644-2013; Hallgrimsson, Benedikt/A-9616-2008; Daniel,
Jeremy/S-4729-2016
OI Calof, Anne/0000-0003-3676-2499; Hallgrimsson,
Benedikt/0000-0002-7192-9103; Daniel, Jeremy/0000-0002-1981-5571
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2010
VL 152A
IS 7
BP 1633
EP 1633
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 628JG
UT WOS:000280115000012
ER
PT J
AU Mahon, PB
Stutz, AM
Seifuddin, F
Huo, YQ
Goes, FS
Jancic, D
Judy, JT
DePaulo, JR
Gershon, ES
McMahon, FJ
Zandi, PP
Potash, JB
Willour, VL
AF Mahon, Pamela B.
Stuetz, Adrian M.
Seifuddin, Fayaz
Huo, Yuqing
Goes, Fernando S.
Jancic, Dubravka
Judy, Jennifer T.
DePaulo, J. Raymond, Jr.
Gershon, Elliot S.
McMahon, Francis J.
Zandi, Peter P.
Potash, James B.
Willour, Virginia L.
TI Case-Control Association Study of TGOLN2 in Attempted Suicide
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE suicidal behavior; bipolar disorder; major depression
ID GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; EARLY-ONSET; GENOTYPE
IMPUTATION; MAJOR DEPRESSION; MENTAL-DISORDERS; LINKAGE SCAN;
SUBSTANCE-P; BEHAVIOR; GENETICS
AB Family, twin, and adoption studies provide convincing evidence for a genetic contribution to suicidal behavior. The heritability for suicidal behavior depends in part on the transmission of psychiatric disorders, such as mood disorders and substance use disorders, but is also partly independent of them. Three linkage studies using the attempted suicide phenotype in pedigrees with bipolar disorder, major depression, or alcoholism have provided consistent evidence that 2p11-12 harbors a susceptibility gene for attempted suicide. A microarray expression study using postmortem brain samples has implicated a gene from the 2p11-12 candidate region, the trans-Golgi network protein 2 (TGOLN2) gene, as being consistently up-regulated in suicide cases as compared to controls. Here, we present a TGOLN2 case control control association study using nine single nucleotide polymorphisms (SNPs). These nine SNPs, which include seven tag SNPs and two coding SNPs, have been genotyped in 517 mood disorder subjects with a history of attempted suicide and 515 normal controls. Allelic and genotypic analyses of the case control sample did not provide evidence for association with the attempted suicide phenotype. Eight of the nine SNPs provided supportive evidence for association (P-values ranging from 0.008 to 0.03) when we compared the attempted suicide cases with a history of alcoholism to the attempted suicide cases without a history of alcoholism. However, this association finding was not replicated in an independent sample. Taken together, these analyses do not provide support for the hypothesis that common genetic variation in TGOLN2 contributes significantly to the risk for attempted suicide in subjects with major mood disorders. (C) 2010 Wiley-Liss, Inc.
C1 [Mahon, Pamela B.; Seifuddin, Fayaz; Huo, Yuqing; Goes, Fernando S.; Jancic, Dubravka; Judy, Jennifer T.; DePaulo, J. Raymond, Jr.; Potash, James B.; Willour, Virginia L.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Stuetz, Adrian M.] European Mol Biol Lab, Dept Genome Biol, Heidelberg, Germany.
[Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Willour, VL (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Meyer 4-132,600 N Wolfe St, Baltimore, MD 21287 USA.
EM willour@jhmi.edu
OI Stuetz, Adrian/0000-0001-7650-3470; McMahon, Francis/0000-0002-9469-305X
FU National Institute of Mental Health [MH079240]; American Foundation for
Suicide Prevention; Margaret Price Investigatorships; NIMH;
Massachusetts General Hospital [MH 63420]
FX Grant sponsor: National Institute of Mental Health; Grant number:
MH079240; Grant sponsor: American Foundation for Suicide Prevention.
Pamela B. Mahon and Adrian M. Stutz contributed equally to this work.;
This work was supported by grants from the National Institute of Mental
Health (MH079240 to V.L.W.) and the American Foundation for Suicide
Prevention to V.L.W. Dr. Willour and Dr. Potash were also supported by
Margaret Price Investigatorships. Some DNA samples were prepared and
distributed by Rutgers University under a contract from the NIMH. We are
grateful to the many interviewers and diagnosticians who contributed to
this project, and to the families who devoted their time and effort to
the study. The Bipolar Disorder Phenome Group consists of Francis
McMahon, Jo Steele, Justin Pearl, Layla Kassem, Victor Lopez from the
Genetic Basis of Mood and Anxiety Disorders Unit, Mood and Anxiety
Program, National Institute of Mental Health, National Institutes of
Health, Bethesda, MD; James Potash, Dean MacKinnon, Erin Miller,
Jennifer Toolan from the Department of Psychiatry, Johns Hopkins School
of Medicine, Baltimore, MD; Peter Zandi from the Department of Mental
Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
Thomas Schulze from the Division of Genetic Epidemiology in Psychiatry,
Central Institute of Mental Health, Ruprecht-Karls-University of
Heidelberg, Mannheim, Germany; Evaristus Nwulia from the Department of
Psychiatry, Howard University Hospital, Washington, DC; Sylvia Simpson
from the Department of Psychiatry, University of Colorado at Denver,
Denver, CO. Acknowledgement for Bipolar Disorder Biomaterials and
Clinical Data: Data and biomaterials were collected in four projects
that participated in the National Institute of Mental Health (NIMH)
Bipolar Disorder Genetics Initiative. From 1991 to 1998, the Principal
Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, U01 MH46282, John Nurnberger, M.D., Ph.D., Marvin
Miller, M.D., and Elizabeth Bowman, M.D.; Washington University, St.
Louis, MO, U01 MH46280, Theodore Reich, M.D., Allison Goate, Ph.D., and
John Rice, Ph.D.; Johns Hopkins University, Baltimore, MD U01 MH46274,
J. Raymond DePaulo Jr, M.D., Sylvia Simpson, M.D., MPH, and Colin Stine,
Ph.D.; NIMH Intramural Research Program, Clinical Neurogenetics Branch,
Bethesda, MD, Elliot Gershon, M.D., Diane Kazuba, B.A., and Elizabeth
Maxwell, M.S.W. Data and biomaterials were collected as part of ten
projects that participated in the National Institute of Mental Health
(NIMH) Bipolar Disorder Genetics Initiative. From 1999 to 2003, the
Principal Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, R01 MH59545, John Nurnberger, M.D., Ph.D., Marvin J.
Miller, M.D., Elizabeth S. Bowman, M.D., N. Leela Rau, M.D., P. Ryan
Moe, M.D., Nalini Samavedy, M.D., Rif El-Mallakh, M.D. (at University of
Louisville), Husseini Manji, M.D. (at Wayne State University), Debra A.
Glitz, M.D. (at Wayne State University), Eric T. Meyer, M.S., Carrie
Smiley, R.N., Tatiana Foroud, Ph.D., Leah Flury, M.S., Danielle M. Dick,
Ph.D., Howard Edenberg, Ph.D.; Washington University, St. Louis, MO, R01
MH059534, John Rice, Ph.D., Theodore Reich, M.D., Allison Goate, Ph.D.,
Laura Bierut, M.D.; Johns Hopkins University, Baltimore, MD, R01
MH59533, Melvin McInnis M.D., J. Raymond DePaulo Jr, M.D., Dean F.
MacKinnon, M.D., Francis M. Mondimore, M.D., James B. Potash, M.D.,
Peter P. Zandi, Ph.D., Dimitrios Avramopoulos, and Jennifer Payne;
University of Pennsylvania, PA, R01 MH59553, Wade Berrettini M.D.,Ph.D.;
University of California at Irvine, CA, R01 MH60068, William Byerley
M.D., and Mark Vawter M.D.; University of Iowa, IA, R01 MH059548,
William Coryell and Raymond Crowe M.D.; ; University f Chicago, IL, R01
MH59535, Elliot Gershon, M.D., Judith Badner Ph.D., Francis McMahon
M.D., Chunyu Liu Ph.D., Alan Sanders M.D., Maria Caserta, Steven
Dinwiddie M.D., Tu Nguyen, Donna Harakal; University of California at
San Diego, CA, R01 MH59567, John Kelsoe, M.D., Rebecca McKinney, B.A.;
Rush University, IL, R01 MH059556, William Scheftner M.D., Howard M.
Kravitz, D.O., M.P.H., Diana Marta, B.S., Annette Vaughn-Brown, MSN, RN,
and Laurie Bederow, MA; NIMH Intramural Research Program, Bethesda, MD,
1Z01MH002810-01, Francis J. McMahon, M.D., Layla Kassem, PsyD, Sevilla
Detera-Wadleigh, Ph.D., Lisa Austin, Ph.D., Dennis L. Murphy, M.D.
Acknowledgement for Depression Sample Biomaterials and Clinical Data:
Data and biomaterials were collected in six projects that participated
in the National Institute of Mental Health (NIMH) Genetics of Recurrent
Early-Onset Depression (GenRED) project. From 1999 to 2003, the
Principal Investigators and Co-Investigators were: New York State
Psychiatric Institute, New York, NY, R01 MH060912, Myrna M. Weissman,
Ph.D. and James K. Knowles, M.D., Ph.D.; University of Pittsburgh,
Pittsburgh, PA, R01 MH060866, George S. Zubenko, M.D., Ph.D. and Wendy
N. Zubenko, Ed.D., R.N., C.S.; Johns Hopkins University, Baltimore, R01
MH059552, J. Raymond DePaulo, M.D., Melvin G. McInnis, M.D., and Dean
MacKinnon, M.D.; University of Pennsylvania, Philadelphia, PA, RO1
MH61686, Douglas F. Levinson, M.D. (GenRED coordinator), Madeleine M.
Gladis, Ph.D., Kathleen Murphy-Eberenz, Ph.D., and Peter Holmans, Ph.D.
(University of Wales College of Medicine); University of Iowa, Iowa
City, IW, R01 MH059542, Raymond R. Crowe, M.D. and William H. Coryell,
M.D.; Rush University Medical Center, Chicago, IL, R01 MH059541-05,
William A. Scheftner, M.D. Rush-Presbyterian. Acknowledgement for
Control Sample Biomaterials and Clinical Data: Control subjects from the
National Institute of Mental Health Schizophrenia Genetics Initiative
(NIMH-GI), data and biomaterials are being collected by the "Molecular
Genetics of Schizophrenia II" (MGS-2) collaboration. The investigators
and coinvestigators are: ENH/Northwestern University, Evanston, IL,
MH059571, Pablo V. Gejman, M.D. (Collaboration Coordinator; PI), Alan R.
Sanders, M.D.; Emory University School of Medicine, Atlanta, GA,MH59587,
Farooq Amin, M.D. (PI); Louisiana State University Health Sciences
Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN, BC, MSN
(PI); University of California-Irvine, Irvine, CA,MH60870, William
Byerley, M.D. (PI); Washington University, St. Louis, MO, U01, MH060879,
C. Robert Cloninger, M.D. (PI); University of Iowa, Iowa, IA,MH59566,
Raymond Crowe, M.D. (PI), Donald Black, M.D.; University of Colorado,
Denver, CO, MH059565, Robert Freedman, M.D. (PI); University of
Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson M.D. (PI);
University of Queensland, Queensland, Australia, MH059588, Bryan Mowry,
M.D. (PI); Mt. Sinai School of Medicine, New York, NY,MH59586, Jeremy
Silverman, Ph.D. (PI). In addition, cord blood samples were collected by
V L Nimgaonkar's group at the University of Pittsburgh, as part of a
multi-institutional collaborative research project with J Smoller, M.D.,
D.Sc. and P Sklar, M.D., Ph.D. (Massachusetts General Hospital) (grant
MH 63420).
NR 41
TC 2
Z9 2
U1 3
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL
PY 2010
VL 153B
IS 5
BP 1016
EP 1023
DI 10.1002/ajmg.b.31068
PG 8
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 617CZ
UT WOS:000279259700004
PM 20468057
ER
PT J
AU Pinheiro, AP
Bulik, CM
Thornton, LM
Sullivan, PF
Root, TL
Bloss, CS
Berrettini, WH
Schork, NJ
Kaye, WH
Bergen, AW
Magistretti, P
Brandt, H
Crawford, S
Crow, S
Fichter, MM
Goldman, D
Halmi, KA
Johnson, C
Kaplan, AS
Keel, PK
Klump, KL
La Via, M
Mitchell, JE
Strober, M
Rotondo, A
Treasure, J
Woodside, DB
AF Pinheiro, Andrea Poyastro
Bulik, Cynthia M.
Thornton, Laura M.
Sullivan, Patrick F.
Root, Tammy L.
Bloss, Cinnamon S.
Berrettini, Wade H.
Schork, Nicholas J.
Kaye, Walter H.
Bergen, Andrew W.
Magistretti, Pierre
Brandt, Harry
Crawford, Steve
Crow, Scott
Fichter, Manfred M.
Goldman, David
Halmi, Katherine A.
Johnson, Craig
Kaplan, Allan S.
Keel, Pamela K.
Klump, Kelly L.
La Via, Maria
Mitchell, James E.
Strober, Michael
Rotondo, Alessandro
Treasure, Janet
Woodside, D. Blake
TI Association Study of 182 Candidate Genes in Anorexia Nervosa
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE single nucleotide polymorphisms; probands; anorexia nervosa; bulimia
nervosa
ID GENOME-WIDE ASSOCIATION; GLUCAGON-LIKE PEPTIDE-2; POPULATION-BASED TWIN;
FALSE DISCOVERY RATE; BODY-MASS INDEX; EATING-DISORDERS;
BULIMIA-NERVOSA; RISK-FACTORS; PSYCHIATRIC-DISORDERS; NICOTINE
DEPENDENCE
AB We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN. (C) 2010 Wiley-Liss, Inc.
C1 [Pinheiro, Andrea Poyastro; Bulik, Cynthia M.; Thornton, Laura M.; Sullivan, Patrick F.; Root, Tammy L.; La Via, Maria] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Bulik, Cynthia M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Bloss, Cinnamon S.; Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Berrettini, Wade H.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Kaye, Walter H.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Magistretti, Pierre] Univ Lausanne, Dept Psychiat, Brain Mind Inst EPFL Lausanne, Ctr Psychiat Neurosci,Med Sch, Lausanne, Switzerland.
[Brandt, Harry; Crawford, Steve] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Crow, Scott] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Fichter, Manfred M.] Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany.
[Fichter, Manfred M.] Univ Munich, Dept Psychiat, D-8000 Munich, Germany.
[Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
[Halmi, Katherine A.] Cornell Univ, Weill Med Coll, Westchester Div, New York Presbyterian Hosp, White Plains, NY USA.
[Johnson, Craig] Laureate Psychiat Clin & Hosp, Tulsa, OK USA.
[Kaplan, Allan S.; Woodside, D. Blake] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Kaplan, Allan S.; Woodside, D. Blake] Toronto Gen Hosp, Univ Hlth Network, Dept Psychiat, Toronto, ON, Canada.
[Keel, Pamela K.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
[Klump, Kelly L.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA.
[Mitchell, James E.] Neuropsychiat Res Inst, Fargo, ND USA.
[Mitchell, James E.] Univ N Dakota, Sch Med & Hlth Sci, Dept Clin Neurosci, Grand Forks, ND 58201 USA.
[Strober, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Rotondo, Alessandro] Univ Pisa, Pisa, Italy.
[Treasure, Janet] Kings Coll London, Inst Psychiat, Eating Disorders Sect, London WC2R 2LS, England.
[Woodside, D. Blake] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
RP Bulik, CM (reprint author), Univ N Carolina, Dept Psychiat, 101 Manning Dr,CB 7160, Chapel Hill, NC 27599 USA.
EM cbulik@med.unc.edu; wkaye@ucsd.edu
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644;
Treasure, Janet/0000-0003-0871-4596
FU National Institutes of Health (NIH) [MH66117, 1U54RR025204-01,
T32MH076694]; Price Foundation of Geneva Switzerland
FX Grant sponsor: National Institutes of Health (NIH); Grant numbers:
MH66117, 1U54RR025204-01, T32MH076694.; The authors thank the Price
Foundation for the support of the clinical collection of participants'
data and biospecimens, genotyping, and data analysis. The authors thank
the staff of the Price Foundation Collaborative Group for their efforts
in participant screening and clinical assessments. The authors are
indebted to the participating families for their contribution of time
and effort in support of this study. This work was supported by the
Price Foundation of Geneva Switzerland. Dr. Strober received support for
his contribution to this manuscript in part by the Franklin Mint Chair
in Eating Disorders. Dr. Schork and Dr. Bloss are supported in part by
National Institutes of Health grant (NIH 1U54RR025204-01). Dr. Root is
supported by National Institutes of Health grant (T32MH076694).
NR 65
TC 44
Z9 48
U1 4
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL
PY 2010
VL 153B
IS 5
BP 1070
EP 1080
DI 10.1002/ajmg.b.31082
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 617CZ
UT WOS:000279259700010
PM 20468064
ER
PT J
AU Clark, EAS
Mele, L
Wapner, RJ
Spong, CY
Sorokin, Y
Peaceman, A
Iams, JD
Leveno, KJ
Harper, M
Caritis, SN
Miodovnik, M
Mercer, BM
Thorp, JM
Ramin, SM
Carpenter, M
Rouse, DJ
AF Clark, Erin A. S.
Mele, Lisa
Wapner, Ronald J.
Spong, Catherine Y.
Sorokin, Yoram
Peaceman, Alan
Iams, Jay D.
Leveno, Kenneth J.
Harper, Margaret
Caritis, Steve N.
Miodovnik, Menachem
Mercer, Brian M.
Thorp, John M.
Ramin, Susan M.
Carpenter, Marshall
Rouse, Dwight J.
CA Eunice Kennedy Shriver Natl Inst
TI Association of fetal inflammation and coagulation pathway gene
polymorphisms with neurodevelopmental delay at age 2 years
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE gene polymorphism; neurodevelopmental delay; single-nucleotide
polymorphism
ID CEREBRAL-PALSY; ANTENATAL CORTICOSTEROIDS; INTERLEUKIN-4 RECEPTOR;
PRETERM INFANTS; ALPHA-GENE; ATOPY; SINGLE; ASTHMA
AB OBJECTIVE: The purpose of this study was to evaluate the association between fetal inflammation and coagulation gene single-nucleotide polymorphisms (SNPs) and neurodevelopmental delay at age 2 years.
STUDY DESIGN: We conducted a case-controlled secondary analysis of a randomized trial of single-vs multiple-course corticosteroids. Multiplex assay assessed 46 SNPs. Cases had mental developmental and/or psychomotor delay at age 2 years. Control subjects had normal neurodevelopment.
RESULTS: One hundred twenty-five cases and 147 control subjects were analyzed. Allele frequencies were different between cases and control subjects for interleukin (IL) 1 beta-511 (P = .009), IL4R-148 (P = .03), IL6-174 (P = .02), and IL6-176 (P = .007). Genotype frequencies were different for IL1 beta-511 (P = .03) and IL6-174 (P = .04). Results for IL1 beta-511, IL4R-148, and IL6-176 remained significant after logistic regression analysis. IL1 beta-511 and IL6-176 minor alleles were associated with increased risk of neurodevelopmental delay (odds ratio, 3.1; 95% confidence interval [CI], 1.2-8.2 and 2.2; 95% CI, 1.2-3.9, respectively). IL4R-148 minor allele was protective (odds ratio, 0.6; 95% CI, 0.4-0.9).
CONCLUSION: Fetal SNPs in IL1 beta, IL-4R, and IL-6 may be associated with neurodevelopmental delay at age 2 years.
C1 [Clark, Erin A. S.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Peaceman, Alan] Northwestern Univ, Chicago, IL 60611 USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Harper, Margaret] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Miodovnik, Menachem] Columbia Univ, New York, NY USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Ramin, Susan M.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Mele, Lisa] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Clark, EAS (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, Suite 2B200,0N 1900 E, Salt Lake City, UT 84132 USA.
EM erin.clark@hsc.utah.edu
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD21410, HD27869, HD27917, HD27860, HD27915, HD34116,
HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512,
HD36801]; National Center for Research Resources [M01-RR-000080]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (HD21410, HD27869, HD27917,
HD27860, HD27915, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544,
HD40545, HD40560, HD40512, HD40485, and HD36801) and M01-RR-000080 from
the National Center for Research Resources.
NR 22
TC 1
Z9 1
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2010
VL 203
IS 1
AR 83.e1
DI 10.1016/j.ajog.2010.01.047
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 617WZ
UT WOS:000279313900034
PM 20417488
ER
PT J
AU Klein, R
Blodi, BA
Meuer, SM
Myers, CE
Chew, EY
Klein, BEK
AF Klein, Ronald
Blodi, Barbara A.
Meuer, Stacy M.
Myers, Chelsea E.
Chew, Emily Y.
Klein, Barbara E. K.
TI The Prevalence of Macular Telangiectasia Type 2 in the Beaver Dam Eye
Study
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; JUXTAFOVEOLAR RETINAL TELANGIECTASIS;
AGE-RELATED MACULOPATHY; VISUAL-ACUITY; MONOZYGOTIC TWINS; 10-YEAR
INCIDENCE; POPULATION; CLASSIFICATION; DEGENERATION; PROGRESSION
AB PURPOSE: To examine the prevalence of macular telangiectasia type 2 and lesions characterizing it.
DESIGN: Population-based cohort study.
METHODS: SETTING: City and township of Beaver Dam, 1988-1990. STUDY POPULATION: A total of 4790 people 43-86 years of age. OBSERVATION PROCEDURE(S): Grading from stereoscopic fundus photographs to measure macular telangiectasia type 2. MAIN OUTCOME MEASURE: Prevalent macular telangiectasia type 2.
RESULTS: Macular telangiectasia type 2 was present at baseline in 0.1% of the population (95% confidence interval [CI] 0.09, 0.1). The frequencies of loss of retinal transparency, crystals in the inner retinal layers, blunted retinal vessels, localized intraretinal pigment migration in the juxtafoveolar region, and presence of yellow deposits and lamellar holes in the foveal area in those without macular telangiectasia type 2 varied from 0.06% for retinal telangiectatic vessels to 1.2% for lamellar holes. Smoking was associated with pigment clumping (odds ratio [OR] per pack year 1.02; 95% CI 1.00, 1.03; P = .02), retinal pigment epithelial (RPE) depigmentation (OR 1.02 per pack year; 95%CI 1.00, 1.04; P = .02), loss of transparency (OR 1.02 per pack year; 95% Cl 1.00, 1.03; P = .008), and the presence of a yellow spot in the fovea (OR 2.24 current vs past or never smoker; 95% Cl 1.29, 3.89; P = .004), but not with presence of macular telangiectasia type 2 (OR 2.72; 95% Cl 0.45, 16.28; P = .27).
CONCLUSIONS: The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought. These data are useful in estimating the burden of this condition in the population. The role of smoking in the development of macular telangiectasia type 2 requires further study. (Am J Ophthalmol 2010;150:55-62. (C) 2010 by Elsevier Inc. All rights reserved.)
C1 [Klein, Ronald; Blodi, Barbara A.; Meuer, Stacy M.; Myers, Chelsea E.; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53726 USA.
[Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
RP Klein, R (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, 610 N Walnut St,Room 417 WARF, Madison, WI 53726 USA.
EM kleinr@epi.ophth.wisc.edu
OI Klein, Ronald/0000-0002-4428-6237
FU NATIONAL INSTITUTE OF HEALTH, BETHESDA, MARYLAND [EY006594]; Lowy
Medical Foundation; Research to Prevent Blindness, New York, New York;
National Institutes of Health [EY006594, DK073217, EY016379, HL069979]
FX THIS RESEARCH IS SUPPORTED BY GRANT NO. EY006594 FROM THE NATIONAL
INSTITUTE OF HEALTH, BETHESDA, MARYLAND; by a grant from the Lowy
Medical Foundation for the MAC TEL Project; and, in part, by Senior
Scientific Investigator Awards from Research to Prevent Blindness, New
York, New York (R.K., B.K.). Dr R. Klein receives grant support from the
National Institutes of Health (grants DK073217, EY016379, EY006594, and
HL069979). Dr B.E. Klein receives grant support from the National
Institutes of Health (EY016379, EY006594). Involved in design and
conduct of the study (R.K.); collection, management, analysis, and
interpretation of the data (R.K., B.B., S.M., CM., E.C., B.K.); and
preparation, review, and/or approval of the manuscript (R.K., B.B.,
S.M., CM., E.C., B.K.). Institutional Review Board approval was granted
by the Health Sciences Institutional Review Board at the University of
Wisconsin, Madison. Written informed consent for the use and disclosure
of protected health information, compliant with the provisions of HIPAA;
was obtained from all subjects before being enrolled in the study.
NR 34
TC 32
Z9 32
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUL
PY 2010
VL 150
IS 1
BP 55
EP 62
DI 10.1016/j.ajo.2010.02.013
PG 8
WC Ophthalmology
SC Ophthalmology
GA 624FW
UT WOS:000279803200011
PM 20609708
ER
PT J
AU Bi, YM
Gao, YM
Ehirchiou, D
Cao, CZ
Kikuiri, T
Le, A
Shi, ST
Zhang, L
AF Bi, Yanming
Gao, Yamei
Ehirchiou, Driss
Cao, Chunzhang
Kikuiri, Takashi
Le, Anh
Shi, Songtao
Zhang, Li
TI Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MEVALONATE PATHWAY; ZOLEDRONIC ACID; IN-VITRO; BONE; CANCER; OSTEOCLAST;
APOPTOSIS; DEXAMETHASONE; DOCETAXEL; THERAPY
AB Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a morbid bone disease linked to long-term bisphosphonate use. Despite its broad health impact, mechanistic study is lacking. In this study, we have established a mouse model of BONJ-like disease based on the equivalent clinical regimen in myeloma patients, a group associated with high risk of BONJ. We demonstrate that the murine BONJ-like disease recapitulates major clinical and radiographical manifestations of the human disease, including characteristic features of osseous sclerosis, sequestra, avascular, and radiopaque alveolar bone in the jaw that persists beyond a normal course of wound healing following tooth extraction. We find that long-term administration of bisphosphonates results in an increase in the size and number of osteoclasts and the formation of giant osteoclast-like cells within the alveolar bone. We show that the development of necrotic bone and impaired soft tissue healing in our mouse model is dependent on long-term use of high-dose bisphosphonates, immunosuppressive and chemotherapy drugs, as well as mechanical trauma. Most importantly, we demonstrate that bisphosphonate is the major cause of BONJ-like disease in mice, mediated in part by its ability to suppress osseous angiogenesis and bone remodeling. The availability of this novel mouse model of BONJ-like disease will help elucidate the pathophysiology of BONJ and ultimately develop novel approaches for prevention and treatment of human BONJ. (Am J Pathol 2010, 177:280-290; DOI: 10.2353/ajpath.2010.090592)
C1 [Gao, Yamei; Ehirchiou, Driss; Cao, Chunzhang; Zhang, Li] Univ Maryland, Sch Med, Dept Physiol, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
[Bi, Yanming] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Kikuiri, Takashi; Le, Anh; Shi, Songtao] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA.
RP Zhang, L (reprint author), Univ Maryland, Sch Med, Dept Physiol, Ctr Vasc & Inflammatory Dis, 800 W Baltimore St, Baltimore, MD 21201 USA.
EM lizhang@som.umaryland.edu
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, National Institutes of Health; NIH [HL054710,
AI078365]
FX Supported in part by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research, National Institutes of
Health and NIH grants HL054710 and AI078365.
NR 26
TC 61
Z9 64
U1 1
U2 8
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2010
VL 177
IS 1
BP 280
EP 290
DI 10.2353/ajpath.2010.090592
PG 11
WC Pathology
SC Pathology
GA 624GM
UT WOS:000279805100030
PM 20472893
ER
PT J
AU Hasko, G
Pacher, P
AF Hasko, Gyoergy
Pacher, Pal
TI Endothelial Nrf2 activation: a new target for resveratrol?
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
ID VASCULAR OXIDATIVE STRESS; SMALL-MOLECULE ACTIVATORS; NF-KAPPA-B;
CALORIC RESTRICTION; LIFE-SPAN; CARDIOVASCULAR COMPLICATIONS;
NITRIC-OXIDE; TNF-ALPHA; IN-VIVO; CELLS
C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Ln,MSC-9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
NR 44
TC 16
Z9 17
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2010
VL 299
IS 1
BP H10
EP H12
DI 10.1152/ajpheart.00436.2010
PG 3
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 612HT
UT WOS:000278888400002
PM 20472762
ER
PT J
AU Ungvari, Z
Bagi, Z
Feher, A
Recchia, FA
Sonntag, WE
Pearson, K
de Cabo, R
Csiszar, A
AF Ungvari, Zoltan
Bagi, Zsolt
Feher, Attila
Recchia, Fabio A.
Sonntag, William E.
Pearson, Kevin
de Cabo, Rafael
Csiszar, Anna
TI Resveratrol confers endothelial protection via activation of the
antioxidant transcription factor Nrf2
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE endothelial cell; gracilis; resveratrol; nuclear factor-E(2)-related
factor-2
ID VASCULAR OXIDATIVE STRESS; NECROSIS-FACTOR-ALPHA; MITOCHONDRIAL
SUPEROXIDE-PRODUCTION; SMALL-MOLECULE ACTIVATORS; NITRIC-OXIDE SYNTHASE;
SMOOTH-MUSCLE-CELLS; KAPPA-B ACTIVATION; TNF-ALPHA; CALORIC RESTRICTION;
CORONARY-ARTERIES
AB Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 299: H18-H24, 2010. First published April 23, 2010; doi:10.1152/ajpheart.00260.2010.-Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood. Using a nuclear factor-E(2)-related factor-2 (Nrf2)/antioxidant response element-driven luciferase reporter gene assay, we found that in cultured coronary arterial endothelial cells, resveratrol, in a dose-dependent manner, significantly increases transcriptional activity of Nrf2. Accordingly, resveratrol significantly upregulates the expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, gamma-glutamylcysteine synthetase, and heme oxygenase-1. Resveratrol treatment also significantly attenuated high glucose (30 mM)-induced mitochondrial and cellular oxidative stress (assessed by flow cytometry using MitoSox and dihydroethidine staining). The aforementioned effects of resveratrol were significantly attenuated by the small interfering RNA downregulation of Nrf2 or the overexpression of Kelch-like erythroid cell-derived protein 1, which inactivates Nrf2. To test the effects of resveratrol in vivo, we used mice fed a high-fat diet (HFD), which exhibit increased vascular oxidative stress associated with an impaired endothelial function. In HFD-fed Nrf2(+/+) mice, resveratrol treatment attenuates oxidative stress (assessed by the Amplex red assay), improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring caspase-3 activity and DNA fragmentation) in branches of the femoral artery. In contrast, the aforementioned endothelial protective effects of resveratrol were diminished in HFD-fed Nrf2(-/-) mice. Taken together, our results indicate that resveratrol both in vitro and in vivo confers endothelial protective effects which are mediated by the activation of Nrf2.
C1 [Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Bagi, Zsolt; Feher, Attila; Recchia, Fabio A.] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Pearson, Kevin; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Pearson, Kevin] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA.
[Recchia, Fabio A.] Scuola St Anna, Sector Med, Pisa, Italy.
RP Ungvari, Z (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM zoltan-ungvari@ouhsc.edu
RI Recchia, Fabio/F-2315-2010; de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institutes of Health (NIH) [HL-077256, P01-AG-11370]; American
Diabetes Association; American Federation for Aging Research
FX This work was supported by National Institutes of Health (NIH) Grants
HL-077256 and P01-AG-11370 and grants from the American Diabetes
Association (to Z. Ungvari), the American Federation for Aging Research
(to A. Csiszar), and the Intramural Research Program of the NIH (to R.
de Cabo).
NR 48
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U1 5
U2 40
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2010
VL 299
IS 1
BP H18
EP H24
DI 10.1152/ajpheart.00260.2010
PG 7
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 612HT
UT WOS:000278888400005
PM 20418481
ER
PT J
AU Nayeem, MA
Zeldin, DC
Boegehold, MA
Morisseau, C
Marowsky, A
Ponnoth, DS
Roush, KP
Falck, JR
AF Nayeem, Mohammed A.
Zeldin, Darryl C.
Boegehold, Matthew A.
Morisseau, Christophe
Marowsky, Anne
Ponnoth, Dovenia S.
Roush, Kevin P.
Falck, John R.
TI Modulation by salt intake of the vascular response mediated through
adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide
hydrolase
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE K-ATP channels; relaxation; contraction; adenosine
ID SENSITIVE K+ CHANNELS; RAT PREGLOMERULAR MICROVESSELS;
SMOOTH-MUSCLE-CELLS; EPOXYEICOSATRIENOIC ACIDS; NITRIC-OXIDE;
BLOOD-PRESSURE; HYPERPOLARIZING FACTOR; RESISTANCE ARTERIES; POTASSIUM
CHANNELS; CYTOCHROME P4502C
AB Nayeem MA, Zeldin DC, Boegehold MA, Morisseau C, Marowsky A, Ponnoth DS, Roush KP, Falck JR. Modulation by salt intake of the vascular response mediated through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase. Am J Physiol Regul Integr Comp Physiol 299: R325-R333, 2010. First published April 28, 2010; doi: 10.1152/ajpregu.00823.2009.-High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% NaCl (HS) or 0.45% NaCl (NS) diet for 4-5 wks, concentration-response curves for ACh, 5'-N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A(2A) adenosine receptor (A(2A) AR) agonist] were obtained with N-omega-nitro-L-arginine methyl ester (L-NAME; nitric oxide inhibitor, 10(-4) M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10(-5) M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10(-5) M], dibromo-dodecenyl-methylsulfimide [DDMS; CYP omega-hydroxylase (CYP4A blocker), 10(-5) M], glibenclamide (K-ATP channel blocker; 10(-5) M) and 5-hydroxyde-canoate (5-HD; mitochondrial-K-ATP channel blocker, 10(-4) M). HS dose response to ACh (10(-7) - 10(-5) M) was not different from NS (P > 0.05). Relaxation to 10(-6) M NECA was greater in the HS group (28.4 +/- 3.9%) than in the NS group (4.1 +/- 2.3%). Relaxation to 10(-6) M CGS-21680 was also greater in HS (27.9 +/- 4.5%) than in NS (4.9 +/- 2.2%). L-NAME was able to block the dose response of ACh (10(-7) - 10(-5) M) equally in both HS and NS (P > 0.05), whereas L-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 +/- 2.0%) and 5-HD (to 8.9 +/- 2.2%), and also abolished by glibenclamide (-1.0 +/- 5.9%). In NS, the CGS-21680 response was increased by AUDA (to 26.3 +/- 3.4%) and DDMS (to 27.2 +/- 3.0%). Compared with NS, HS vessels showed increased CYP2J2 and A(2A) AR expression (46 and 74% higher, respectively) but decreased sEH, CYP4A, and A(1) AR expression (75, 30, and 55% lower, respectively). These data suggest that in mice fed NS-containing diet, upregulation of arterial A(1) receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A(2A) receptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.
C1 [Nayeem, Mohammed A.; Boegehold, Matthew A.; Ponnoth, Dovenia S.; Roush, Kevin P.] W Virginia Univ, Dept Physiol & Pharmacol, Ctr Cardiovasc & Resp Sci, Morgantown, WV 26506 USA.
[Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Durham, NC USA.
[Morisseau, Christophe] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Morisseau, Christophe] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA.
[Marowsky, Anne] Inst Pharmakol & Toxikol, Zurich, Switzerland.
[Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
RP Nayeem, MA (reprint author), W Virginia Univ, Dept Physiol & Pharmacol, Ctr Cardiovasc & Resp Sci, 3051 Robert C Byrd Hlth Sci Ctr N,1 Med Ctr Dr PO, Morgantown, WV 26506 USA.
EM mnayeem@hsc.wvu.edu
RI Nayeem, Mohammed/A-3949-2017;
OI Nayeem, Mohammed/0000-0002-7827-4760; Falck, John/0000-0002-9219-7845
FU National Heart, Lung, and Blood Institute [HL-027339, HL-094447];
American Heart Association [2250298]; National Institute of General
Medical Sciences [GM-31278]; National Institute of Environmental Health
Sciences/National Institutes of Health [Z01-ES-025034]
FX This study was supported by National Heart, Lung, and Blood Institute
Grants HL-027339 (to S. J. Mustafa) and HL-094447 (to S. J. Mustafa and
M. A. Nayeem, coinvestigator), American Heart Association Grant 2250298
(to M. A. Boegehold), National Institute of General Medical Sciences
Grant GM-31278 (to J. R. Falck Jr), and the Intramural Research Program
of the National Institute of Environmental Health Sciences/National
Institutes of Health Grant Z01-ES-025034 (to D. C. Zeldin).
NR 56
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U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD JUL
PY 2010
VL 299
IS 1
BP R325
EP R333
DI 10.1152/ajpregu.00823.2009
PG 9
WC Physiology
SC Physiology
GA 616FR
UT WOS:000279194900034
PM 20427718
ER
PT J
AU Insel, T
Cuthbert, B
Garvey, M
Heinssen, R
Pine, DS
Quinn, K
Sanislow, C
Wang, P
AF Insel, Thomas
Cuthbert, Bruce
Garvey, Marjorie
Heinssen, Robert
Pine, Daniel S.
Quinn, Kevin
Sanislow, Charles
Wang, Philip
TI Research Domain Criteria (RDoC): Toward a New Classification Framework
for Research on Mental Disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID SCHIZOPHRENIA
C1 [Insel, Thomas; Cuthbert, Bruce; Garvey, Marjorie; Heinssen, Robert; Pine, Daniel S.; Quinn, Kevin; Sanislow, Charles; Wang, Philip] NIMH, Bethesda, MD 20892 USA.
RP Cuthbert, B (reprint author), NIMH, 6001 Execut Blvd,MSC 9632, Bethesda, MD 20892 USA.
EM bcuthber@mail.nih.gov
NR 8
TC 1275
Z9 1286
U1 18
U2 110
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2010
VL 167
IS 7
BP 748
EP 751
DI 10.1176/appi.ajp.2010.09091379
PG 4
WC Psychiatry
SC Psychiatry
GA 619KO
UT WOS:000279429300006
PM 20595427
ER
PT J
AU Cornwell, BR
Salvadore, G
Colon-Rosario, V
Latov, DR
Holroyd, T
Carver, FW
Coppola, R
Manji, HK
Zarate, CA
Grillon, C
AF Cornwell, Brian R.
Salvadore, Giacomo
Colon-Rosario, Veronica
Latov, David R.
Holroyd, Tom
Carver, Frederick W.
Coppola, Richard
Manji, Husseini K.
Zarate, Carlos A., Jr.
Grillon, Christian
TI Abnormal Hippocampal Functioning and Impaired Spatial Navigation in
Depressed Individuals: Evidence From Whole-Head Magnetoencephalography
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID MORRIS WATER TASK; MOOD DISORDERS; THETA-RHYTHM; MEMORY; PERFORMANCE;
GLUCOCORTICOIDS; NEUROGENESIS; METAANALYSIS; IMPAIRMENTS; DIFFERENCE
AB Objective: Dysfunction of the hippocampus has long been suspected to be a key component of the pathophysiology of major depressive disorder. Despite evidence of hippocampal structural abnormalities in depressed patients, abnormal hippocampal functioning has not been demonstrated. The authors aimed to link spatial navigation deficits previously documented in depressed patients to abnormal hippocampal functioning using a virtual reality navigation task.
Method: Whole-head magnetoencephalography (MEG) recordings were collected while participants (19 patients diagnosed with major depressive disorder and 19 healthy subjects matched by gender and age) navigated a virtual Morris water maze to find a hidden platform; navigation to a visible platform served as a control condition. Behavioral measures were obtained to assess navigation performance. Theta oscillatory activity (4-8 Hz) was mapped across the brain on a voxel-wise basis using a spatial-filtering MEG source analysis technique.
Results: Depressed patients performed worse than healthy subjects in navigating to the hidden platform. Robust group differences in theta activity were observed in right medial temporal cortices during navigation, with patients exhibiting less engagement of the anterior hippocampus and parahippocampal cortices relative to comparison subjects. Left posterior hippocampal theta activity was positively correlated with individual performance within each group.
Conclusions: Consistent with previous findings, depressed patients showed impaired spatial navigation. Dysfunction of right anterior hippocampus and parahippocampal cortices may underlie this deficit and stem from structural abnormalities commonly found in depressed patients. (Am J Psychiatry 2010; 167:836-844)
C1 [Cornwell, Brian R.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
NIMH, Magnetoencephalog Core Facil, Bethesda, MD 20892 USA.
RP Cornwell, BR (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM cornwellb@mail.nih.gov
FU NIMH, National Institutes of Health; National Alliance for Research on
Schizophrenia and Depression
FX Supported by the NIMH Intramural Research Program, National Institutes
of Health, and a National Alliance for Research on Schizophrenia and
Depression award to Dr. Zarate.
NR 40
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U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2010
VL 167
IS 7
BP 836
EP 844
DI 10.1176/appi.ajp.2009.09050614
PG 9
WC Psychiatry
SC Psychiatry
GA 619KO
UT WOS:000279429300018
PM 20439387
ER
PT J
AU Becker, KG
AF Becker, Kevin G.
TI AUTISM AND URBANIZATION
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Letter
ID ENVIRONMENTAL MERCURY RELEASE; TEXAS; PREVALENCE; DISORDER; ASTHMA;
RATES
C1 NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
RP Becker, KG (reprint author), NIA, Gene Express & Genom Unit, NIH, Suite 100,Room 4B122,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM beckerk@grc.nia.nih.gov
OI Becker, Kevin/0000-0002-6794-6656
FU Intramural NIH HHS
NR 11
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U1 0
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1156
EP 1157
DI 10.2105/AJPH.2009.191007
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000001
PM 20466946
ER
PT J
AU Mabry, PL
Marcus, SE
Clark, PI
Leischow, SJ
Mendez, D
AF Mabry, Patricia L.
Marcus, Stephen E.
Clark, Pamela I.
Leischow, Scott J.
Mendez, David
TI Systems Science: A Revolution in Public Health Policy Research
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID DYNAMICS; IMPACT
C1 [Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Marcus, Stephen E.] NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA.
[Clark, Pamela I.] Univ Maryland, Sch Publ Hlth, Dept Publ & Community Hlth, College Pk, MD 20742 USA.
[Leischow, Scott J.] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA.
[Leischow, Scott J.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Mendez, David] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA.
RP Mabry, PL (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31,Room B1-C19,MSC 2027, Bethesda, MD 20892 USA.
EM mabryp@od.nih.gov
NR 13
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U1 1
U2 5
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1161
EP 1163
DI 10.2105/AJPH.2010.198176
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000007
PM 20530757
ER
PT J
AU Marcus, SE
Leischow, SJ
Mabry, PL
Clark, PI
AF Marcus, Stephen E.
Leischow, Scott J.
Mabry, Patricia L.
Clark, Pamela I.
TI Lessons Learned From the Application of Systems Science to Tobacco
Control at the National Cancer Institute
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Marcus, Stephen E.] NCI, NIH, Bethesda, MD 20892 USA.
[Leischow, Scott J.] Univ Arizona, Coll Med, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Leischow, Scott J.] Univ Arizona, Coll Publ Hlth, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Clark, Pamela I.] Univ Maryland, Sch Publ Hlth, Dept Publ & Community Hlth, College Pk, MD 20742 USA.
RP Marcus, SE (reprint author), Natl Inst Gen Med Sci, NIH, 45 Ctr Dr,Room 2As 55A,MSC 6200, Bethesda, MD 20892 USA.
EM marcusst@mail.nih.gov
NR 7
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U1 0
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PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1163
EP 1165
DI 10.2105/AJPH.2010.198721
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000008
PM 20530758
ER
PT J
AU Fee, E
AF Fee, Elizabeth
TI Jules Schevitz (1897-1922): Boy Wonder From Brooklyn
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Biographical-Item
C1 Natl Lib Med, Div Hist Med, NIH, Bethesda, MD 20894 USA.
RP Fee, E (reprint author), Natl Lib Med, Div Hist Med, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
NR 1
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PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1205
EP 1205
DI 10.2105/AJPH.2009.185736
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000013
PM 20466948
ER
PT J
AU Fee, E
Bu, LP
AF Fee, Elizabeth
Bu, Liping
TI The Origins of Public Health Nursing: The Henry Street Visiting Nurse
Service
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Fee, Elizabeth] Natl Lib Med, Div Hist Med, NIH, Bethesda, MD USA.
[Bu, Liping] Alma Coll, Dept Hist, Alma, MI USA.
RP Fee, E (reprint author), Care of Chang BB, Hist Med Div, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM changb@mail.nih.gov
NR 3
TC 7
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U1 0
U2 0
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1206
EP 1207
DI 10.2105/AJPH.2009.186049
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000014
PM 20466947
ER
PT J
AU Levy, DT
Mabry, PL
Graham, AL
Orleans, CT
Abrams, DB
AF Levy, David T.
Mabry, Patricia L.
Graham, Amanda L.
Orleans, C. Tracy
Abrams, David B.
TI Exploring Scenarios to Dramatically Reduce Smoking Prevalence: A
Simulation Model of the Three-Part Cessation Process
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID NICOTINE REPLACEMENT THERAPIES; TOBACCO-CONTROL; PUBLIC-HEALTH;
CIGARETTE USE; SMOKERS QUIT; POLICIES; ABSTINENCE; DEATHS; IMPACT;
METAANALYSIS
AB Objectives. We used a simulation model to analyze whether the Healthy People 2010 goal of reducing smoking prevalence from the current 19.8% rate to 12% by 2010 could be accomplished by increasing quit attempts, increasing the use of treatments, or increasing the effectiveness of treatment.
Methods. We expanded on previous versions of the tobacco control simulation model SimSmoke to assess the effects of an increase in quit attempts, treatment use, and treatment effectiveness to reduce smoking prevalence. In the model, we considered increases in each of these parameters individually and in combination.
Results. Individually, 100% increases in quit attempts, treatment use, and treatment effectiveness reduced the projected 2020 prevalence to 13.9%, 16.7%, and 15.9%, respectively. With a combined 100% increase in all components, the goal of a 12% adult smoking prevalence could be reached by 2012.
Conclusions. If we are to come close to reaching Healthy People 2010 goals in the foreseeable future, we must not only induce quit attempts but also increase treatment use and effectiveness. Simulation models provide a useful tool for evaluating the potential to reach public health targets. (Am J Public Health. 2010; 100:1253-1259. doi:10.2105/AJPH.2009.166785)
C1 [Levy, David T.] Pacific Inst Res & Evaluat, Calverton, MD 20705 USA.
[Levy, David T.] Univ Baltimore, Baltimore, MD 21201 USA.
[Mabry, Patricia L.; Abrams, David B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Graham, Amanda L.] Amer Legacy Fdn, Steven A Schroeder Inst Tobacco Res & Policy Stud, Washington, DC USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA.
RP Levy, DT (reprint author), Pacific Inst Res & Evaluat, 11720 Beltsville Dr,Suite 900, Calverton, MD 20705 USA.
EM levy@pire.org
OI Graham, Amanda/0000-0003-3036-9653
FU National Tobacco Cessation Collaborative's Consumer Demand Roundtable;
National Institutes of Health, Office of Behavioral and Social Sciences
Research (OBSSR) [HHSN 276200700294P]; Robert Wood Johnson Foundation
(RWJF); Cancer Intervention and Surveillance Modeling Network (CISNET)
of the Division of Cancer Control and Population Sciences, National
Cancer Institute [UO1-CA97450-02]
FX This article was conducted under the auspices of the National Tobacco
Cessation Collaborative's Consumer Demand Roundtable and was supported
by funds provided by the National Institutes of Health, Office of
Behavioral and Social Sciences Research (OBSSR, contract # HHSN
276200700294P) and the Robert Wood Johnson Foundation (RWJF). David T.
Levy also received funding from the Cancer Intervention and Surveillance
Modeling Network (CISNET) of the Division of Cancer Control and
Population Sciences, National Cancer Institute (grant UO1-CA97450-02).
NR 56
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PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2010
VL 100
IS 7
BP 1253
EP 1259
DI 10.2105/AJPH.2009.166785
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 610SO
UT WOS:000278756000022
PM 20466969
ER
PT J
AU DiGiulio, DB
Romero, R
Kusanovic, JP
Gomez, R
Kim, CJ
Seok, KS
Gotsch, F
Mazaki-Tovi, S
Vaisbuch, E
Sanders, K
Bik, EM
Chaiworapongsa, T
Oyarzun, E
Relman, DA
AF DiGiulio, Daniel B.
Romero, Roberto
Kusanovic, Juan Pedro
Gomez, Ricardo
Kim, Chong Jai
Seok, Kimberley S.
Gotsch, Francesca
Mazaki-Tovi, Shali
Vaisbuch, Edi
Sanders, Katherine
Bik, Elisabeth M.
Chaiworapongsa, Tinnakorn
Oyarzun, Enrique
Relman, David A.
TI Preterm premature rupture of the membranes: current approaches to
evaluation and management
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
ID AMNIOTIC-FLUID INTERLEUKIN-6; POLYMERASE-CHAIN-REACTION; FETAL
INFLAMMATORY RESPONSE; BLOOD-CELL COUNT; ACTIVATING PEPTIDE-1
INTERLEUKIN-8; HUMAN SUBGINGIVAL PLAQUE; RAPID DIAGNOSTIC-TESTS;
TUMOR-NECROSIS-FACTOR; REAL-TIME PCR; INTRAAMNIOTIC INFECTION
C1 [Romero, Roberto; Kusanovic, Juan Pedro; Kim, Chong Jai; Gotsch, Francesca; Mazaki-Tovi, Shali; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA.
[Romero, Roberto; Kusanovic, Juan Pedro; Kim, Chong Jai; Gotsch, Francesca; Mazaki-Tovi, Shali; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, Bethesda, MD USA.
[DiGiulio, Daniel B.; Seok, Kimberley S.; Sanders, Katherine; Bik, Elisabeth M.; Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[DiGiulio, Daniel B.; Relman, David A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Romero, Roberto; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp,Detroit Med Ctr, Detroit, MI 48201 USA.
[Gomez, Ricardo] Hosp Dr Sotero del Rio, CEDIP Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Santiago, Chile.
[Gomez, Ricardo; Oyarzun, Enrique] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Sanders, Katherine; Bik, Elisabeth M.; Relman, David A.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, 3990 John R,4 Brush S, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; relman@stanford.edu
FU National Institute of Child Health and Human Development, NIH, DHHS;
March of Dimes Foundation; NIH [NIH DP1OD000964]
FX This work was supported, in part, by the Intramural Research Program of
the National Institute of Child Health and Human Development, NIH, DHHS,
and by a grant from the March of Dimes Foundation to DAR. DAR is
supported by an NIH Director's Pioneer Award (NIH DP1OD000964).
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PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUL
PY 2010
VL 64
IS 1
BP 38
EP 57
DI 10.1111/j.1600-0897.2010.00830.x
PG 20
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 606BP
UT WOS:000278395800008
PM 20331587
ER
PT J
AU Wright, RJ
Visness, CM
Calatroni, A
Grayson, MH
Gold, DR
Sandel, MT
Lee-Parritz, A
Wood, RA
Kattan, M
Bloomberg, GR
Burger, M
Togias, A
Witter, FR
Sperling, RS
Sadovsky, Y
Gern, JE
AF Wright, Rosalind J.
Visness, Cynthia M.
Calatroni, Agustin
Grayson, Mitchell H.
Gold, Diane R.
Sandel, Megan T.
Lee-Parritz, Aviva
Wood, Robert A.
Kattan, Meyer
Bloomberg, Gordon R.
Burger, Melissa
Togias, Alkis
Witter, Frank R.
Sperling, Rhoda S.
Sadovsky, Yoel
Gern, James E.
TI Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine
Responses in an Inner-City Cohort
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE psychological stress; cord blood; cytokines; innate; adaptive
ID RESPIRATORY SYNCYTIAL VIRUS; T-REGULATORY CELLS; IMMUNE-RESPONSES;
AIRWAY INFLAMMATION; DENDRITIC CELLS; ASTHMA; MATURATION; PREGNANCY;
ALLERGENS; CHILDREN
AB Rationale: Stress-elicited disruption of immunity begins in utero.
Objectives: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).
Methods: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).
Measurements and Main Results Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-a to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced
Conclusions Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.
C1 [Wright, Rosalind J.; Gold, Diane R.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Med Sch, Boston, MA 02115 USA.
[Wright, Rosalind J.; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Visness, Cynthia M.; Calatroni, Agustin] Rho Inc, Chapel Hill, NC USA.
[Sandel, Megan T.; Lee-Parritz, Aviva] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Grayson, Mitchell H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Kattan, Meyer] Columbia Univ, Med Ctr, New York, NY USA.
[Wood, Robert A.; Witter, Frank R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Burger, Melissa; Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Bloomberg, Gordon R.] Washington Univ, St Louis Sch Med, St Louis, MO USA.
[Sperling, Rhoda S.] Mt Sinai Sch Med, New York, NY USA.
[Sadovsky, Yoel] Magee Womens Res Inst, Pittsburgh, PA USA.
[Togias, Alkis] NIAID, Bethesda, MD 20892 USA.
RP Wright, RJ (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM rerjw@channing.harvard.edu
OI Lee-Parritz, Aviva/0000-0003-4655-7720
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-AI-25482]; National Center for
Research Resources, National Institutes of Health [RR00052, M01RR00533,
M01RR00071, 5 UL1RR024992-02]; National Institutes of Health [R01
HL080674]; Genentech
FX Supported by the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, under contracts NO1-AI-25496 and
NO1-AI-25482, and by the National Center for Research Resources,
National Institutes of Health grants RR00052, M01RR00533, M01RR00071,
and 5 UL1RR024992-02. During preparation of this manuscript R.J.W. was
also supported by National Institutes of Health grant R01 HL080674.;
R.J.W. does not have a financial relationship with a commercial entity
that has an interest in the subject of this manuscript. C.M.V. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. A.C. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. M.H.G. received 550,001-$100,000 from
Genentech as an investigator-initiated research grant. D.R.G. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. M.T.S. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. At-P. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. R.A.W. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. M.K. does not have a financial relationship
with a commercial entity that has an interest in the subject of this
manuscript. G.R.B. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. M.B. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. AT. is an employee of the National Institutes of Health.
F.R.W. does not have a financial relationship with a commercial entity
that has an interest in the subject of this manuscript. R.S.S. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. Y.S. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. J.E.G. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript.
NR 59
TC 93
Z9 94
U1 4
U2 12
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL 1
PY 2010
VL 182
IS 1
BP 25
EP 33
DI 10.1164/rccm.200904-0637OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 623AP
UT WOS:000279709200007
PM 20194818
ER
PT J
AU Cho, HY
Gladwell, W
Wang, XT
Chorley, B
Be, D
Reddy, SP
Kleeberger, SR
AF Cho, Hye-Youn
Gladwell, Wesley
Wang, Xuting
Chorley, Brian
Be, Douglas
Reddy, Sekhar P.
Kleeberger, Steven R.
TI Nrf2-regulated PPAR gamma Expression Is Critical to Protection against
Acute Lung Injury in Mice
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE antioxidant response element; hyperoxia; inflammation; siRNA; 15d-PGJ(2)
ID ACTIVATED-RECEPTOR-GAMMA; OBSTRUCTIVE PULMONARY-DISEASE; ANTIOXIDANT
RESPONSE ELEMENTS; NRF2 ENHANCES SUSCEPTIBILITY;
INFLAMMATORY-BOWEL-DISEASE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2);
AIRWAY INFLAMMATION; ALLERGIC INFLAMMATION; HEME OXYGENASE-1;
GENE-EXPRESSION
AB Rationale: The NF-E2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is essential for protection against oxidative injury and inflammation including hyperoxia-induced acute lung injury. Microarray expression profiling revealed that lung peroxisome proliferator activated receptor gamma (PPAR gamma) induction is suppressed in hyperoxia-susceptible Nrf2-deficient (Nrf2(-/-)) mice compared with wild-type (Nrf2(+/+)) mice. PPAR gamma has pleiotropic beneficial effects including antiinflammation in multiple tissues.
Objectives: We tested the hypothesis that PPAR gamma is an important determinant of pulmonary responsivity to hyperoxia regulated by Nrf2.
Methods: A computational bioinformatic method was applied to screen potential AREs in the Pparg promoter for Nrf2 binding. The functional role of a potential ARE was investigated by in vitro promoter analysis. A role for PPAR gamma in hyperoxia-induced acute lung injury was determined by temporal silencing of PPART via intranasal delivery of PPAR-y-specific interference RNA and by administration of a PPAR gamma ligand 15-deoxy-Delta(12,14) prostaglandin J(2) in mice.
Measurements and Main Results: Deletion or site-directed mutagenesis of a potential ARE spanning -784/-764 sequence significantly attenuated hyperoxia-increased Pparg promoter activity in airway epithelial cells overexpressing Nrf2, indicating that the -784/-764 ARE is critical for Nrf2-regulated PPAR gamma expression. Mice with decreased lung PPAR gamma by specific interference RNA treatment had significantly augmented hyperoxia-induced pulmonary inflammation and injury. 15 Deoxy-Delta(12,14)- prostaglandin J(2) administration significantly reduced hyperoxia-induced lung inflammation and edema in Nrf2(+/+), but not in Nrf2(-/-) mice.
Conclusions: Results indicate for the first time that Nrf2-driven PPAR gamma induction has an essential protective role in pulmonary oxidant injury. Our observations provide new insights into the therapeutic potential of PPAR gamma in airway oxidative inflammatory disorders.
C1 [Cho, Hye-Youn; Gladwell, Wesley; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Wang, Xuting; Chorley, Brian; Be, Douglas] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Reddy, Sekhar P.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA.
EM cho2@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health, Department of Health and Human Services [HL66109]
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, and in part by grant HL66109
(S.P.R.).
NR 81
TC 67
Z9 74
U1 0
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL
PY 2010
VL 182
IS 2
BP 170
EP 182
DI 10.1164/rccm.200907-1047OC
PG 13
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 629NN
UT WOS:000280206700008
PM 20224069
ER
PT J
AU Mahavadi, P
Korfei, M
Henneke, I
Liebisch, G
Schmitz, G
Gochuico, BR
Markart, P
Bellusci, S
Seeger, W
Ruppert, C
Guenther, A
AF Mahavadi, Poornima
Korfei, Martina
Henneke, Ingrid
Liebisch, Gerhard
Schmitz, Gerd
Gochuico, Bernadette R.
Markart, Philipp
Bellusci, Saverio
Seeger, Werner
Ruppert, Clemens
Guenther, Andreas
TI Epithelial Stress and Apoptosis Underlie Hermansky-Pudlak
Syndrome-associated Interstitial Pneumonia
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE pulmonary surfactant; biogenesis of lysosome-related organelle complex;
adaptor protein-3; apoptosis; cathepsin D
ID ENDOPLASMIC-RETICULUM STRESS; LYSOSOME-RELATED ORGANELLES;
CHEDIAK-HIGASHI-SYNDROME; PULMONARY-FIBROSIS; OXIDATIVE STRESS;
PROTEIN-C; HERMANSKY-PUDLAK-SYNDROME-1 HPS1; COMPLEX-3 BLOC-3; SYNDROME
TYPE-1; II PNEUMOCYTES
AB Rationale. The molecular mechanisms underlying Hermansky-Pudlak syndrome associated interstitial pneumonia (HPSIP) are poorly understood but, as in idiopathic pulmonary fibrosis, may be linked to chronic alveolar epithelial type II cell (AECII) injury.
Objectives: We studied the development of fibrosis and the role of AECII injury in various murine models of HPS.
Methods: HPS1, HPS2, and HPS6 monomutant mice, and HPS1/2 and HPS1/6 double-mutant and genetic background mice, were killed at 3 and 9 months of age. Quantitative morphometry was undertaken in lung sections stained with hemalaun eosin. The extent of lung fibrosis was assessed by trichrome staining and hydroxyproline measurement. Surfactant lipids were analyzed by electrospray ionization mass spectrometry. Surfactant proteins, apoptosis, and lysosomal and endoplasmic reticulum stress markers were studied by Western blotting and immunohistochemistry. Cell proliferation was measured by water-soluble tetrazolium salt-1 and bromodeoxyuridine assays.
Measurements and Main Results: Spontaneous and slowly progressive HPSIP was observed in HPS1/2 double mutants, but not in other HPS mutants, with subpleural onset at 3 months and full-blown fibrosis at 9 months. In these mice, extensive surfactant abnormalities were encountered in AECII and were paralleled by early lysosomal stress (cathepsin D induction), late endoplasmic reticulum stress (activating transcription factor-4 [ATF4], C/EBP homologous protein [CHOP] induction), and marked apoptosis. These findings were fully corroborated in human HPSIP. In addition, cathepsin D overexpression resulted in apoptosis of MLE-12 cells and increased proliferation of NIH 3T3 fibroblasts incubated with conditioned medium of the transfected cells.
Conclusions: Extensively impaired surfactant trafficking and secretion underlie lysosomal and endoplasmic reticulum stress with apoptosis of AECII in HPSIP, thereby causing the development of HPSIP.
C1 [Mahavadi, Poornima; Korfei, Martina; Henneke, Ingrid; Markart, Philipp; Seeger, Werner; Ruppert, Clemens; Guenther, Andreas] Univ Giessen, Lung Ctr, Dept Internal Med 2, D-35392 Giessen, Germany.
[Liebisch, Gerhard; Schmitz, Gerd] Univ Regensburg, Inst Clin Chem & Lab Med, D-93042 Regensburg, Germany.
[Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Guenther, Andreas] Lung Clin Waldhof Elgershausen, Greifenstein, Germany.
RP Guenther, A (reprint author), Univ Giessen, Lung Ctr, Dept Internal Med 2, Klin Str 36, D-35392 Giessen, Germany.
EM Guenther@uglc.de
RI Liebisch, Gerhard/G-6130-2010;
OI Liebisch, Gerhard/0000-0003-4886-0811; Schmitz, Gerd/0000-0002-1325-1007
FU European Commission; European Lipidomics Initiative; German Research
Council; National Human Genome Research Institute, National Institutes
of Health, Bethesda, MD
FX Supported by research grants from the European Commission through FP7
(European IPF Network [www.pulmonary-fibrosis.net] and European
Lipidomics Initiative [www.lipidomics.net]), the German Research Council
(Clinical Research Group 118 "Lung Fibrosis" and Excellence Cluster
"Cardiopulmonary System" [www.eccps.de]), and in part by the Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health, Bethesda, MD.
NR 61
TC 32
Z9 32
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL
PY 2010
VL 182
IS 2
BP 207
EP 219
DI 10.1164/rccm.200909-1414OC
PG 13
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 629NN
UT WOS:000280206700012
PM 20378731
ER
PT J
AU Balamayooran, G
Batra, S
Fessler, MB
Happel, KI
Jeyaseelan, S
AF Balamayooran, Gayathriy
Batra, Sanjay
Fessler, Michael B.
Happel, Kyle I.
Jeyaseelan, Samithamby
TI Mechanisms of Neutrophil Accumulation in the Lungs Against Bacteria
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Review
DE bacterial pneumonia; lung inflammation; acute lung injury
ID TUMOR-NECROSIS-FACTOR; ESCHERICHIA-COLI PNEUMONIA; COMMUNITY-ACQUIRED
PNEUMONIA; ACUTE ETHANOL INTOXICATION; INNATE IMMUNE-RESPONSES;
PULMONARY HOST-DEFENSE; NF-KAPPA-B; MYELOID DIFFERENTIATION FACTOR-88;
STIMULATING FACTOR RESPONSE; CONTAINING ADAPTER PROTEIN
AB Bacterial lung diseases are a major cause of morbidity and mortality both in immunocompromised and in immunocompetent individuals. Neutrophil accumulation, a pathological hallmark of bacterial diseases, is critical to host defense, but may also cause acute lung injury/acute respiratory distress syndrome. Toll-like receptors, nucleotide-binding oligomerization domain (NOD)-like receptors, transcription factors, cytokines, and chemokines play essential roles in neutrophil sequestration in the lungs. This review highlights our current understanding of the role of these molecules in the lungs during bacterial infection and their therapeutic potential. We also discuss emerging data on cholesterol and ethanol as environmentally modifiable factors that may impact neutrophil-mediated pulmonary innate host defense. Understanding the precise molecular mechanisms leading to neutrophil influx in the lungs during bacterial infection is critical for the development of more effective therapeutic and prophylactic strategies to control the excessive host response to infection.
C1 [Balamayooran, Gayathriy; Batra, Sanjay; Jeyaseelan, Samithamby] Louisiana State Univ, Dept Pathobiol Sci, Lab Lung Biol, Baton Rouge, LA 70803 USA.
[Balamayooran, Gayathriy; Batra, Sanjay; Jeyaseelan, Samithamby] Louisiana State Univ, Ctr Expt Infect Dis Res, Baton Rouge, LA 70803 USA.
[Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Happel, Kyle I.; Jeyaseelan, Samithamby] LSU Hlth Sci Ctr, Dept Med, Pulm & Crit Care Med Sect, New Orleans, LA USA.
RP Jeyaseelan, S (reprint author), Louisiana State Univ, Dept Pathobiol Sci, Lab Lung Biol, Baton Rouge, LA 70803 USA.
EM jey@lsu.edu
RI Sawant, Kirti/H-3778-2013
FU American Lung Association [RG-22442-N]; Flight Attendant Medical
Research Institute [YCSA-062466]; National Institutes of Health [R01
HL-091958, K08 AA15163]; NIH/NIEHS
FX This work was supported by a research grant from the American Lung
Association (RG-22442-N to S.J.), a scientist award from the Flight
Attendant Medical Research Institute (YCSA-062466 to S.J.). grants from
the National Institutes of Health (R01 HL-091958 to S.J., K08 AA15163 to
K.I.H.); and the Intramural Research Program of the NIH/NIEHS (to
M.B.F.).
NR 142
TC 50
Z9 50
U1 0
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL
PY 2010
VL 43
IS 1
BP 5
EP 16
DI 10.1165/rcmb.2009-0047TR
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 623BX
UT WOS:000279713400002
PM 19738160
ER
PT J
AU Fayad, LM
Wang, X
Salibi, N
Barker, PB
Jacobs, MA
Machado, AJ
Weber, KL
Bluemke, DA
AF Fayad, Laura M.
Wang, Xin
Salibi, Nouha
Barker, Peter B.
Jacobs, Michael A.
Machado, Antonio J.
Weber, Kristy L.
Bluemke, David A.
TI A Feasibility Study of Quantitative Molecular Characterization of
Musculoskeletal Lesions by Proton MR Spectroscopy at 3 T
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE bone mass; MRI; MR spectroscopy; musculoskeletal neoplasm; soft-tissue
mass
ID SOFT-TISSUE TUMORS; IN-VIVO QUANTIFICATION; INTERNAL REFERENCE; BREAST;
MUSCLE; BRAIN; WATER; BONE; METABOLITES; CONTRAST
AB OBJECTIVE. The purpose of this study is to establish the feasibility and potential value of measuring the concentration of choline-containing compounds by proton MR spectroscopy (MRS) in musculoskeletal lesions at 3 T.
SUBJECTS AND METHODS. Thirty-three subjects with 34 musculoskeletal lesions (four histologically proven malignant, 13 histologically proven benign or proven benign by follow-up analysis, and 17 posttreatment fibrosis with documented stability for 6-36 months) underwent single-voxel 3-T MRS studies. In each case, both water-suppressed and water-un-suppressed scans were obtained. The quality of the scans was recorded as excellent, adequate, or nondiagnostic, and the choline concentration was measured using water as the internal reference. The choline concentrations of benign and malignant lesions were compared using the Mann-Whitney test.
RESULTS. Spectral quality was excellent in 26 cases, adequate in four cases, and nondiagnostic in four cases. For malignant lesions (three sarcomas), the choline concentrations were 1.5, 2.9, and 3.8 mmol/kg, respectively. For five benign lesions (two neurofibromas, two schwannomas, and one enchondroma), the choline concentrations were 0.11, 0.28, 0.13, 0.8, and 1.2 mmol/kg, respectively. For seven benign lesions (two hematomas, two bone cysts, one lipoma, one giant cell tumor, and one pigmented villonodular synovitis), the spectra showed negligible choline content. For three posttreatment fibrosis cases, the choline concentration range was 0.2-0.4 mmol/kg. For the remaining 12 posttreatment fibrosis cases, the spectra showed negligible choline content. Average choline concentrations were different for malignant and benign lesions (2.7 vs 0.5 mmol/kg; p = 0.01).
CONCLUSION. The measurement of choline concentration within musculoskeletal lesions by MRS is feasible using an internal water-referencing method at 3 T and has potential for characterizing lesions for malignancy.
C1 [Fayad, Laura M.; Wang, Xin; Barker, Peter B.; Machado, Antonio J.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Salibi, Nouha] Siemens Healthcare USA, Res Collaborat, MR Spect, Earth City, MO USA.
[Jacobs, Michael A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Div MR Res, Baltimore, MD 21205 USA.
[Weber, Kristy L.] Johns Hopkins Med Inst, Dept Orthopaed Surg, Baltimore, MD 21287 USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Fayad, LM (reprint author), Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Wolfe St,MRI 143C, Baltimore, MD 21287 USA.
EM lfayad1@jhmi.edu
RI Jacobs, Michael/G-2901-2010; wang, xin/I-3395-2013;
OI wang, xin/0000-0002-9519-8413; Bluemke, David/0000-0002-8323-8086
FU Society of Body CT; MRI; William M. G. Gatewood Fellowship [2007]; GE
Healthcare-Association of University Radiologists Radiology Research
Academic Fellowship [2008]; National Institutes of Health [1R01CA100184,
P50CA103175]
FX This work was supported by the Society of Body CT and MRI (2004 Young
Investigator's Award), the 2007 William M. G. Gatewood Fellowship, the
2008 GE Healthcare-Association of University Radiologists Radiology
Research Academic Fellowship, and the National Institutes of Health
(grants 1R01CA100184 and P50CA103175).
NR 26
TC 19
Z9 19
U1 2
U2 3
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUL
PY 2010
VL 195
IS 1
BP W69
EP W75
DI 10.2214/AJR.09.3718
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 613RQ
UT WOS:000278998200049
PM 20566784
ER
PT J
AU Miller, DL
Simon, SL
Thierry-Chef, I
Land, CE
AF Miller, Donald L.
Simon, Steven L.
Thierry-Chef, Isabelle
Land, Charles E.
TI Stochastic and Deterministic Risk in Children Undergoing
Neurointerventional Procedures
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Letter
ID INTERVENTIONAL RADIOLOGY PROCEDURES; RAD-IR; NEURORADIOLOGY; CANCER
C1 [Miller, Donald L.] Natl Naval Med Ctr, Bethesda, MD USA.
[Miller, Donald L.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
[Simon, Steven L.; Land, Charles E.] NCI, Bethesda, MD 20892 USA.
[Thierry-Chef, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
RP Miller, DL (reprint author), Natl Naval Med Ctr, Bethesda, MD USA.
NR 13
TC 1
Z9 1
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUL
PY 2010
VL 195
IS 1
BP W87
EP W88
DI 10.2214/AJR.09.4180
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 613RQ
UT WOS:000278998200055
PM 20566788
ER
PT J
AU Gillespie, BW
Merion, RM
Ortiz-Rios, E
Tong, L
Shaked, A
Brown, RS
Ojo, AO
Hayashi, PH
Berg, CL
Abecassis, MM
Ashworth, AS
Friese, CE
Hong, JC
Trotter, JF
Everhart, JE
AF Gillespie, B. W.
Merion, R. M.
Ortiz-Rios, E.
Tong, L.
Shaked, A.
Brown, R. S.
Ojo, A. O.
Hayashi, P. H.
Berg, C. L.
Abecassis, M. M.
Ashworth, A. S.
Friese, C. E.
Hong, J. C.
Trotter, J. F.
Everhart, J. E.
CA A2ALL Study Grp
TI Database Comparison of the Adult-to-Adult Living Donor Liver
Transplantation Cohort Study (A2ALL) and the SRTR US Transplant Registry
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Data validation; database; live donor transplantation; liver
transplantation; quality assessment
ID IMMUNOSUPPRESSION REGIMENS; RECIPIENTS; ALLOCATION; REGRESSION;
REJECTION; MORBIDITY; OUTCOMES; CLAIMS
AB Data submitted by transplant programs to the Organ Procurement and Transplantation Network (OPTN) are used by the Scientific Registry of Transplant Recipients (SRTR) for policy development, performance evaluation and research. This study compared OPTN/SRTR data with data extracted from medical records by research coordinators from the nine-center A2ALL study. A2ALL data were collected independently of OPTN data submission (48 data elements among 785 liver transplant candidates/recipients; 12 data elements among 386 donors). At least 90% agreement occurred between OPTN/SRTR and A2ALL for 11/29 baseline recipient elements, 4/19 recipient transplant or follow-up elements and 6/12 donor elements. For the remaining recipient and donor elements, > 10% of values were missing in OPTN/SRTR but present in A2ALL, confirming that missing data were largely avoidable. Other than variables required for allocation, the percentage missing varied widely by center. These findings support an expanded focus on data quality control by OPTN/SRTR for a broader variable set than those used for allocation. Center-specific monitoring of missing values could substantially improve the data.
C1 [Gillespie, B. W.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Merion, R. M.; Tong, L.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Ortiz-Rios, E.] US Hlth Resources & Serv Adm, Div Transplantat, US Dept HHS, Bethesda, MD USA.
[Shaked, A.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Brown, R. S.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Ojo, A. O.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Hayashi, P. H.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA.
[Berg, C. L.] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA USA.
[Abecassis, M. M.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA.
[Ashworth, A. S.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA.
[Friese, C. E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Hong, J. C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Trotter, J. F.] Univ Colorado, Dept Surg, Aurora, CO USA.
[Everhart, J. E.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA.
RP Gillespie, BW (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
EM bgillesp@umich.edu
RI Abecassis, Michael/F-7977-2011
FU National Institute of Diabetes & Digestive & Kidney Diseases; Health
Resources and Services Administration (HRSA); American Society of
Transplant Surgeons (ASTS); National Institutes of Health (NIDDK)
[U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484,
U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531]
FX This study was supported by National Institute of Diabetes & Digestive &
Kidney Diseases through cooperative agreements (listed below).
Additional support was provided by Health Resources and Services
Administration (HRSA), and the American Society of Transplant Surgeons
(ASTS). This study was supported in part by the National Institutes of
Health (NIDDK grant numbers U01-DK62536, U01-DK62444, U01-DK62467,
U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498,
U01-DK62505, U01-DK62531). The following individuals were instrumental
in the planning, conduct and/or care of patients enrolled in this study
at each of the participating institutions as follows: Columbia
University Health Sciences, New York, NY (DK62483). PI: Jean C. Emond,
MD; Co-PI: Robert S. Brown, Jr., MD, MPH; study coordinators: Rudina
Odeh-Ramadan, PharmD; Scott Heese, BA; Northwestern University, Chicago,
IL (DK62467). PI: Michael M.I. Abecassis, MD, MBA; Co-PI: Laura M.
Kulik, MD; study coordinator: Patrice Al-Saden, RN, CCRC; University of
Pennsylvania Health System, Philadelphia, PA (DK62494): PI: Abraham
Shaked, MD, PhD; Co-PI: Kim M. Olthoff, MD; Study Coordinators: Brian
Conboy, PA, MBA; Mary Shaw, RN, BBA; University of Colorado Health
Sciences Center, Denver, CO (DK62536). PI: Gregory T. Everson, MD;
Co-PI: Igal Kam, MD; study coordinators: Carlos Garcia, BS, Anastasia
Krajec, RN; University of California Los Angeles, Los Angeles, CA
(DK62496). PI: Johnny C. Hong, MD; Co-PI: Ronald W. Busuttil, MD, PhD;
study coordinator: Janet Mooney, RN, BSN; University of California San
Francisco, San Francisco, CA (DK62444). PI: Chris E. Freise, MD, FACS;
Co-PI: Norah A. Terrault, MD; study coordinator: Dulce MacLeod, RN;
Vivian Tan, MD; University of Michigan Medical Center, Ann Arbor, MI
(DK62498). PI: Robert M. Merion, MD; DCC Staff: Anna S.F. Lok, MD;
Akinlolu O. Ojo, MD, PhD; Brenda W. Gillespie, PhD; Margaret
Hill-Callahan, BS, LSW; Terese Howell, BS; Lan Tong, MS; Tempie H.
Shearon, MS; Karen A. Wisniewski, MPH; Monique Lowe, BS; Abby Smith, BA;
University of North Carolina, Chapel Hill, NC (DK62505). PI: Paul H.
Hayashi, MD, MPH; study coordinator: Tracy Russell, MA; University of
Virginia (DK62484). PI: Carl L. Berg, MD; Co-PI: Timothy L. Pruett, MD;
study coordinator: Jaye Davis, RN; Medical College of Virginia
Hospitals, Virginia Commonwealth University, Richmond, VA (DK62531). PI:
Robert A. Fisher, MD, FACS; Co-PI: Mitchell L. Shiffman, MD; study
coordinators: Andrea Lassiter; April Ashworth, RN; National Institute of
Diabetes and Digestive and Kidney Diseases, Division of Digestive
Diseases and Nutrition, Bethesda, MD. James E. Everhart, MD, MPH;
Leonard B. Seeff, MD; Patricia R. Robuck, PhD; Jay H. Hoofnagle, MD.
Supplemental data included here have been supplied by the Arbor Research
Collaborative for Health as the contractor for the Scientific Registry
of Transplant Recipients (SRTR). The interpretation and reporting of
these data are the responsibility of the author(s) and in no way should
be seen as an official policy of or interpretation by the SRTR or the
U.S. Government.
NR 22
TC 26
Z9 26
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2010
VL 10
IS 7
BP 1621
EP 1633
DI 10.1111/j.1600-6143.2010.03039.x
PG 13
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 615SD
UT WOS:000279155900020
PM 20199501
ER
PT J
AU Kalil, AC
Mattei, J
Florescu, DF
Sun, J
Kalil, RS
AF Kalil, A. C.
Mattei, J.
Florescu, D. F.
Sun, J.
Kalil, R. S.
TI Recommendations for the Assessment and Reporting of Multivariable
Logistic Regression in Transplantation Literature
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Review
DE Logistic; multivariable; regression; transplantation
ID QUALITY-OF-LIFE; BRONCHIOLITIS OBLITERANS SYNDROME; ORTHOTOPIC
LIVER-TRANSPLANTATION; CHRONIC ALLOGRAFT NEPHROPATHY; LEFT-VENTRICULAR
HYPERTROPHY; CLINICAL-PREDICTION RULES; STEM-CELL TRANSPLANTATION;
CORONARY-ARTERY-DISEASE; BONE-MINERAL DENSITY; RISK-FACTORS
AB Multivariable logistic regression is an important method to evaluate risk factors and prognosis in solid organ transplant literature. We aimed to assess the quality of this method in six major transplantation journals. Eleven analytical criteria and four documentation criteria were analyzed for each selected article that used logistic regression. A total of 106 studies (6%) out of 1,701 original articles used logistic regression analyses from January 1, 2005 to January 1, 2006. The analytical criteria and their respective reporting percentage among the six journals were: Linearity (25%); Beta coefficient (48%); Interaction tests (19%); Main estimates (98%); Ovefitting prevention (84%); Goodness-of-fit (3.8%); Multicolinearity (4.7%); Internal validation (3.8%); External validation (8.5%). The documentation criteria were reported as follows: Selection of independent variables (73%); Coding of variables (9%); Fitting procedures (49%); Statistical program (65%). No significant differences were found among different journals or between general versus subspecialty journals with respect to reporting quality. We found that the report of logistic regression is unsatisfactory in transplantation journals. Because our findings may have major consequences for the care of transplant patients and for the design of transplant clinical trials, we recommend a practical solution for the use and reporting of logistic regression in transplantation journals.
C1 [Kalil, A. C.; Florescu, D. F.] Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE 68198 USA.
[Mattei, J.] Hosp Nossa Senhora Conceicao, Porto Alegre, RS, Brazil.
[Sun, J.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Kalil, R. S.] Univ Iowa Hosp & Clin, Div Nephrol, Iowa City, IA 52242 USA.
RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE 68198 USA.
EM akalil@unmc.edu
FU National Heart and Lung and Blood Institute (NHLBI ) [5K23 HL08410-02];
National Kidney Foundation (NKF)
FX We thank Ms. Elaine Litton for providing outstanding administrative
work. R.S.K. is supported by a grant from the National Heart and Lung
and Blood Institute (NHLBI # 5K23 HL08410-02) and by a Clinician
Scientist Award from the National Kidney Foundation (NKF). Funding
sources: None.
NR 120
TC 13
Z9 15
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2010
VL 10
IS 7
BP 1686
EP 1694
DI 10.1111/j.1600-6143.2010.03141.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 615SD
UT WOS:000279155900027
PM 20642690
ER
PT J
AU Mills, LA
Nakigoz, G
Gray, RH
Quinn, TC
Reynolds, SJ
AF Mills, Lisa A.
Nakigoz, Gertrude
Gray, Ronald H.
Quinn, Thomas C.
Reynolds, Steven J.
TI Utility of Point-of-Care Malaria Rapid Diagnostic Tests Response
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Letter
C1 [Mills, Lisa A.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Nakigoz, Gertrude] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Quinn, Thomas C.; Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Mills, LA (reprint author), Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
EM lmills@ke.cdc.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUL
PY 2010
VL 83
IS 1
BP 208
EP 208
DI 10.4269/ajtmh.2010.10-0114b
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 618OU
UT WOS:000279366300039
ER
PT J
AU Brown, PN
Chan, M
Betz, JM
AF Brown, Paula N.
Chan, Michael
Betz, Joseph M.
TI Optimization and single-laboratory validation study of a
high-performance liquid chromatography (HPLC) method for the
determination of phenolic Echinacea constituents
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Echinacea; Phenolic; Chromatography; Method validation; Quality control
ID DIETARY-SUPPLEMENTS; COMMON COLD
AB Three species of Echinacea (Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida) are commonly used for medicinal purposes. The phenolic compounds caftaric acid, cichoric acid, echinacoside, cynarin, and chlorogenic acid are among the phytochemical constituents that may be responsible for the purported beneficial effects of the herb. Although methods for the analysis for these compounds have been published, documentation of their validity was inadequate as the accuracy and precision for the detection and quantification of these phenolics was not systematically determined and/or reported. To address this issue, the high-performance liquid chromatography method, originally developed by the Institute for Nutraceutical Advancement (INA), was reviewed, optimized, and validated for the detection and quantification of these phenolic compounds in Echinacea roots and aerial parts.
C1 [Brown, Paula N.; Chan, Michael] British Columbia Inst Technol, Burnaby, BC V5G 3H2, Canada.
[Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Brown, PN (reprint author), British Columbia Inst Technol, 3700 Willingdon Ave, Burnaby, BC V5G 3H2, Canada.
EM Paula_Brown@bcit.ca
NR 25
TC 9
Z9 11
U1 2
U2 12
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUL
PY 2010
VL 397
IS 5
BP 1883
EP 1892
DI 10.1007/s00216-010-3763-z
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 611IY
UT WOS:000278810000030
PM 20467727
ER
PT J
AU Gray, TR
Barnes, AJ
Huestis, MA
AF Gray, Teresa R.
Barnes, Allan J.
Huestis, Marilyn A.
TI Effect of hydrolysis on identifying prenatal cannabis exposure
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article; Proceedings Paper
CT 6th International Conference on Instrumental Methods of Analysis
CY OCT 04-08, 2009
CL Athens, GREECE
DE Cannabinoids; Meconium; Hydrolysis; Glucuronide conjugates;
beta-glucuronidase
ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; MAJOR METABOLITES; MASS-SPECTROMETRY;
GC-MS; MECONIUM; DELTA(9)-TETRAHYDROCANNABINOL; DELTA(9)-THC; URINE;
PHARMACOKINETICS; QUANTIFICATION
AB Identification of prenatal cannabis exposure is important due to potential cognitive and behavioral consequences. A two-dimensional gas chromatography-mass spectrometry method for cannabinol, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8 beta,11-dihydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) quantification in human meconium was developed and validated. Alkaline, enzymatic, and enzyme-alkaline tandem hydrolysis conditions were optimized with THC- and THCCOOH-glucuronide reference standards. Limits of quantification ranged from 10 to 15 ng/g, and calibration curves were linear to 500 ng/g. Bias and intra-day and inter-day imprecision were < 12.3%. Hydrolysis efficiencies were analyte-dependent; THC-glucuronide was effectively cleaved by enzyme, but not base. Conversely, THCCOOH-glucuronide was most sensitive to alkaline hydrolysis. Enzyme-alkaline tandem hydrolysis maximized efficiency for both glucuronides. Identification of cannabinoid-positive meconium specimens nearly doubled following alkaline and enzyme-alkaline hydrolysis. Although no 11-OH-THC glucuronide standard is available, enzymatic hydrolysis improved 11-OH-THC detection in authentic specimens. Maximal identification of cannabis-exposed neonates and the widest range of cannabis biomarkers are achieved with enzyme-alkaline tandem hydrolysis.
C1 [Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS [ZIA DA000433-11]
NR 17
TC 12
Z9 12
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUL
PY 2010
VL 397
IS 6
BP 2335
EP 2347
DI 10.1007/s00216-010-3772-y
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 619TK
UT WOS:000279453000036
PM 20517601
ER
PT J
AU Ye, XY
Luke, BT
Johann, DJ
Ono, A
Prieto, DA
Chan, KC
Issaq, HJ
Veenstra, TD
Blonder, J
AF Ye, Xiaoying
Luke, Brian T.
Johann, Donald J., Jr.
Ono, Akira
Prieto, DaRue A.
Chan, King C.
Issaq, Haleem J.
Veenstra, Timothy D.
Blonder, Josip
TI Optimized Method for Computing (18)O/(16)O Ratios of Differentially
Stable-Isotope Labeled Peptides in the Context of Postdigestion (18)O
Exchange/Labeling
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID VIRUS TYPE-1 GAG; CATALYZED O-16-TO-O-18 EXCHANGE; QUANTITATIVE
PROTEOMICS DATA; MASS-SPECTROMETRY; MEMBRANE-PROTEINS; IDENTIFICATION;
SOFTWARE; TRYPSIN; MULTIMERIZATION; ELECTROSPRAY
AB Differential (18)O/(16)O stable isotope labeling of peptides that relies on enzyme-catalyzed oxygen exchange at their carboxyl termini in the presence of H(2)(18)O has been widely used for relative quantitation of peptides/proteins. The role of tryptic proteolysis in bottom-up shotgun proteomics and low reagent costs have made trypsin-catalyzed (18)O postdigestion exchange a convenient and affordable stable isotope labeling approach. However, it is known that trypsin-catalyzed (18)O exchange at the carboxyl terminus is in many instances inhomogeneous/incomplete. The extent of the (18)O exchange/incorporation fluctuates from peptide to peptide mostly due to variable enzyme-substrate affinity. Thus, accurate calculation and interpretation of peptide ratios are analytically complicated and in some regard deficient. Therefore, a computational approach capable of improved measurement of actual (18)O incorporation for each differentially labeled peptide pair is needed. In this regard, we have developed an algorithmic method that relies on the trapezoidal rule to integrate peak intensities of all detected isotopic species across a particular peptide ion over the retention time, which fits the isotopic manifold to Poisson distributions. Optimal values for manifold fitting were calculated and then (18)O/(16)O ratios derived via evolutionary programming. The algorithm is tested using trypsin-catalyzed (18)O postdigestion exchange to differentially label bovine serum albumin (BSA) at a priori determined ratios. Both accuracy and precision are improved utilizing this rigorous mathematical approach. We further demonstrate the effectiveness of this method to accurately calculate (18)O/(16)O ratios in a large scale proteomic quantitation of detergent resistant membrane microdomains (DM/Ms) isolated from cells expressing wild-type HIV-1 Gag and its nonmyristylated mutant.
C1 [Ye, Xiaoying; Prieto, DaRue A.; Chan, King C.; Issaq, Haleem J.; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Luke, Brian T.] NCI, Adv Biomed Comp Ctr, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Johann, Donald J., Jr.] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Ono, Akira] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48109 USA.
RP Blonder, J (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA.
EM blonder@ncifcrf.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E, 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
Contracts HHSN261200800001E and 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
United States Government.
NR 36
TC 12
Z9 12
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD JUL 1
PY 2010
VL 82
IS 13
BP 5878
EP 5886
DI 10.1021/ac101284c
PG 9
WC Chemistry, Analytical
SC Chemistry
GA 617AO
UT WOS:000279253300064
PM 20540505
ER
PT J
AU Ozden, O
Black, BL
Ashwell, CM
Tipsmark, CK
Borski, RJ
Grubb, BJ
AF Ozden, Ozkan
Black, Betty L.
Ashwell, Christopher M.
Tipsmark, Christian K.
Borski, Russell J.
Grubb, Brenda J.
TI Developmental Profile of Claudin-3,-5, and-16 Proteins in the Epithelium
of Chick Intestine
SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY
BIOLOGY
LA English
DT Article
DE claudin proteins; tight junctions; intestine; goblet cells; chick embryo
ID TIGHT JUNCTION PROTEINS; SUBCELLULAR-LOCALIZATION; DIFFERENTIAL
EXPRESSION; MOUSE; OVEREXPRESSION; STRANDS; HYDROCORTISONE;
HETEROGENEITY; PARACELLIN-1; THYROXINE
AB Proteins in the claudin family are a main component of tight junctions and form a seal that modulates paracellular transport in intestinal epithelium. This research tests the hypothesis that claudins 3, 5, and 16 will appear in the epithelium of embryonic intestine during functional differentiation. Immunohistochemistry is utilized to explore the developmental patterns of claudin-3, -5, and -16 proteins in the epithelium of embryonic chick intestine from 9 days prior to hatching through the early post-hatch period. These claudin proteins either changed their cellular localization or first appeared around the time of hatching. After hatching, claudin-3 expression was prominent in basal lateral regions of the epithelium along the entire villus, but was absent from crypts. Claudin-5 was expressed most strongly in the crypt and lower villus epithelium within junctional complexes, whereas immunostaining of claudin-16 was localized within goblet cells of the upper villus region. The relative mRNA levels of claudin-3, -5, and -16 showed similar patterns; transcript levels rose between 18 and 20 days of development, then dropped by 2 days post-hatch. Results of this work indicate that the claudin proteins assume their final locations within the epithelium around the time of hatching, suggesting that in addition to their known barrier and fence functions within tight junctions, these claudins may have additional roles in the differentiation and/or physiological function of chick intestine. The localization of claudin-16 to goblet cells and its distribution in the more mature cells of the upper villus region suggest an unexpected role in goblet cell maturation and mucus secretion. Anat Rec, 293:1175-1183, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Black, Betty L.; Borski, Russell J.; Grubb, Brenda J.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA.
[Ozden, Ozkan] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ashwell, Christopher M.] N Carolina State Univ, Dept Poultry Sci, Raleigh, NC 27695 USA.
[Tipsmark, Christian K.] Univ So Denmark, Inst Biol, Odense M, Denmark.
RP Black, BL (reprint author), N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA.
EM betty_black@ncsu.edu
FU North Carolina Agricultural Research Service [NC06726]
FX Grant sponsor: North Carolina Agricultural Research Service; Grant
number: NC06726.
NR 43
TC 9
Z9 11
U1 5
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1932-8486
J9 ANAT REC
JI Anat. Rec.
PD JUL
PY 2010
VL 293
IS 7
BP 1175
EP 1183
DI 10.1002/ar.21163
PG 9
WC Anatomy & Morphology
SC Anatomy & Morphology
GA 630ZU
UT WOS:000280316800009
PM 20583258
ER
PT J
AU Macellini, S
Ferrari, PF
Bonini, L
Fogassi, L
Paukner, A
AF Macellini, Sara
Ferrari, Pier Francesco
Bonini, Luca
Fogassi, Leonardo
Paukner, Annika
TI A modified mark test for own-body recognition in pig-tailed macaques
(Macaca nemestrina)
SO ANIMAL COGNITION
LA English
DT Article
DE Mirror self-recognition; Mark test; Pigtail macaque; Macaca nemestrina
ID MIRROR-SELF-RECOGNITION; MONKEYS CEBUS-APELLA; PAN-TROGLODYTES; IMAGE
RESPONSES; CHIMPANZEES; THEMSELVES; GORILLAS; BEHAVIOR
AB Classic mirror self-recognition mark tests involve familiarizing the subject with its mirror image, surreptitiously applying a mark on the subject's eyebrow, nose, or ear, and measuring self-directed behaviors toward the mark. For many non-human primate species, however, direct gaze at the face constitutes an aggressive and threatening signal. It is therefore possible that monkeys fail the mark test because they do not closely inspect their faces in a mirror and hence they have no expectations about their physical appearance. In the current study, we prevented two pig-tailed macaques (Macaca nemestrina) from seeing their own faces in a mirror, and we adopted a modified version of the classic mark test in which monkeys were marked on the chest, a body region to which they normally have direct visual access but that in the current study was visible only via a mirror. Neither monkey tried to touch the mark on its chest, possibly due to a failure to understand the mirror as a reflective surface. To further the monkeys' understanding of the mirror image, we trained them to reach for food using the mirror as the only source of information. After both monkeys had learned mirror-mediated reaching, we replicated the mark test. In this latter phase of the study, only one monkey scratched the red dye on the chest once. The results are consistent with other findings suggesting that monkeys are not capable of passing a mark test and imply that face and body recognition rely on the same cognitive abilities.
C1 [Macellini, Sara; Bonini, Luca; Fogassi, Leonardo] Univ Parma, Dipartimento Neurosci, Sez Fisiol, I-43100 Parma, Italy.
[Ferrari, Pier Francesco; Fogassi, Leonardo] Univ Parma, Dipartimento Psicol, I-43100 Parma, Italy.
[Macellini, Sara; Ferrari, Pier Francesco] Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy.
[Paukner, Annika] NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA.
RP Macellini, S (reprint author), Univ Parma, Dipartimento Neurosci, Sez Fisiol, Via Volturno 39, I-43100 Parma, Italy.
EM sara.macellini@nemo.unipr.it
FU Intramural NIH HHS [Z99 HD999999]
NR 36
TC 9
Z9 11
U1 3
U2 21
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1435-9448
J9 ANIM COGN
JI Anim. Cogn.
PD JUL
PY 2010
VL 13
IS 4
BP 631
EP 639
DI 10.1007/s10071-010-0313-1
PG 9
WC Behavioral Sciences; Zoology
SC Behavioral Sciences; Zoology
GA 611IZ
UT WOS:000278810100004
PM 20148344
ER
PT J
AU Hasan, R
Baird, DD
Herring, AH
Olshan, AF
Funk, MLJ
Hartmann, KE
AF Hasan, Reem
Baird, Donna D.
Herring, Amy H.
Olshan, Andrew F.
Funk, Michele L. Jonsson
Hartmann, Katherine E.
TI Patterns and Predictors of Vaginal Bleeding in the First Trimester of
Pregnancy
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Miscarriage; Vaginal Bleeding
ID GESTATIONAL-AGE; 1ST-TRIMESTER; ULTRASOUND; BIRTH; OUTCOMES; RISK
AB PURPOSE: Although first-trimester vaginal bleeding is an alarming symptom, few studies have investigated the prevalence and predictors of early bleeding. This study characterizes first trimester bleeding, setting aside bleeding that occurs at time of miscarriage.
METHODS: Participants (n = 4539) were women ages 18 to 45 enrolled in Right From the Start, a community-based pregnancy study (2000-2008). Bleeding information included timing, heaviness, duration, color, and associated pain. Life table analyses were used to describe gestational timing of bleeding. Factors associated with bleeding were investigated by the use of multiple logistic regression with multiple imputation for missing data.
RESULTS: Approximately one fourth of participants (n = 1207) reported bleeding (n = 1656 episodes), but only 8% of women with bleeding reported heavy bleeding. Of the spotting and light bleeding episodes (n = 1555), 28% were associated with pain. Among heavy episodes (n = 100), 54% were associated with pain. Most episodes lasted less than 3 days, and most occurred between gestational weeks 5 to 8. Twelve percent of women with bleeding and 13% of those without experienced miscarriage. Maternal characteristics associated with bleeding included fibroids and prior miscarriage.
CONCLUSIONS: Consistent with the hypothesis that bleeding is a marker for placental dysfunction, bleeding is most likely to be observed around the time of the luteal-placental shift. Ann Epidemiol 2010;20:524-531. Published by Elsevier Inc.
C1 [Hasan, Reem; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Hasan, Reem; Olshan, Andrew F.; Funk, Michele L. Jonsson] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Herring, Amy H.; Olshan, Andrew F.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA.
RP Hasan, R (reprint author), NIEHS, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA.
EM reem_hasan@med.unc.edu
RI Jonsson Funk, Michele/F-6885-2011; Baird, Donna/D-5214-2017
OI Jonsson Funk, Michele/0000-0002-3756-7540; Baird,
Donna/0000-0002-5544-2653
FU National Institute of Child and Human Development [5R01HD043883,
5R01HD049675]; American Water Works Association Research Foundation
[2579]; National Institute of Environmental Health Sciences [P30ES10126]
FX The field research was supported in part by grants from the National
Institute of Child and Human Development (5R01HD043883 and 5R01HD049675)
and the American Water Works Association Research Foundation (2579).
Additional funds were provided by the National Institute of
Environmental Health Sciences (Intramural Research Program and
P30ES10126).
NR 21
TC 17
Z9 18
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUL
PY 2010
VL 20
IS 7
BP 524
EP 531
DI 10.1016/j.annepidem.2010.02.006
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 614FZ
UT WOS:000279042100004
PM 20538195
ER
PT J
AU Doubeni, CA
Laiyemo, AO
Young, AC
Klabunde, CN
Reed, G
Field, TS
Fletcher, RH
AF Doubeni, Chyke A.
Laiyemo, Adeyinka O.
Young, Angela C.
Klabunde, Carrie N.
Reed, George
Field, Terry S.
Fletcher, Robert H.
TI Primary Care, Economic Barriers to Health Care, and Use of Colorectal
Cancer Screening Tests Among Medicare Enrollees Over Time
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE Colorectal cancer; cancer screening tests; health care disparities; cost
of health care; insurance; health; physician's practice patterns
ID UNITED-STATES; PREVENTIVE SERVICES; INSURANCE; PATIENT; POPULATION;
PATTERNS; ADULTS; PARTICIPATION; COLONOSCOPY; DISPARITIES
AB PURPOSE Colorectal cancer (CRC) screening remains underutilized. The objective of this study was to examine the impact of primary care and economic barriers to health care on CRC testing relative to the 2001 Medicare expansion of screening coverage.
METHODS Medicare Current Beneficiary Survey data were use to study community-dwelling enrollees aged 65 to 80 years, free of renal disease and CRC, and who participated in the survey in 2000 (n = 8,330), 2003 (n = 7,889), or 2005 (n = 7,614). Three outcomes were examined: colonoscopy/sigmoidoscopy within 5 years (recent endoscopy), endoscopy more than 5 years previously, and fecal occult blood test (FOBT) within 2 years.
RESULTS Endoscopy use increased and FOBT use decreased during the 6-year period, with no significant independent differences between those receiving care from primary care physicians and those receiving care from other physicians. Beneficiaries without a usual place of health care were the least likely to undergo CRC testing, and that gap widened with time: adjusted odds ratio (AOR) = 0.27 (95% confidence interval [CI], 0.19-0.39) for FOBT, and AOR = 0.35 (95% CI, 0.27-0.46) for endoscopy in 2000 compared with AOR = 0.18 (95% CI, 0.11-0.30) for FOBT and AOR = 0.22 (95% CI, 0.17-0.30) for endoscopy in 2005. Disparities in use of recent endoscopy by type of health insurance coverage in both 2000 and 2005 were greater for enrollees with a high school education or higher than they were for less-educated enrollees. There were no statistically significant differences by delayed care due to cost after adjustment for health insurance.
CONCLUSION Despite expanding coverage for screening, complex CRC screening disparities persisted based on differences in the usual place and cost of health care, type of health insurance coverage, and level of education.
C1 [Doubeni, Chyke A.; Young, Angela C.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA.
[Doubeni, Chyke A.; Field, Terry S.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Clin, Worcester, MA USA.
[Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Reed, George] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA.
[Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
RP Doubeni, CA (reprint author), Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, 55 Lake Ave N, Worcester, MA 01655 USA.
EM Chyke.Doubeni@umassmed.edu
OI Doubeni, Chyke/0000-0001-7495-0285
FU National Cancer Institute [5K01CA127118-03]
FX Dr Doubeni is supported by a National Cancer Institute career
development award (5K01CA127118-03).
NR 46
TC 33
Z9 33
U1 2
U2 5
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
J9 ANN FAM MED
JI Ann. Fam. Med.
PD JUL-AUG
PY 2010
VL 8
IS 4
BP 299
EP 307
DI 10.1370/afm.1112
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 634YQ
UT WOS:000280622600004
PM 20644184
ER
PT J
AU Varghese, S
Xu, HI
Bartlett, D
Hughes, M
Pingpank, JF
Beresnev, T
Alexander, HR
AF Varghese, Sheelu
Xu, Hui
Bartlett, David
Hughes, Marybeth
Pingpank, James F.
Beresnev, Tatiana
Alexander, H. Richard, Jr.
TI Isolated Hepatic Perfusion with High-Dose Melphalan Results in Immediate
Alterations in Tumor Gene Expression in Patients with Metastatic Ocular
Melanoma
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID LOCAL CHROMATIN-STRUCTURE; UVEAL MELANOMA; NECROSIS-FACTOR; ARTERIAL
CHEMOEMBOLIZATION; LIVER METASTASES; TYROSINASE; PROGNOSIS; REPAIR; MITF
AB Patients with ocular melanoma liver metastases have a poor prognosis, treatment options are limited, and median survival is less than 1 year. In this study, we characterized the early molecular changes that occur in tumors immediately after vascular isolation perfusion with melphalan with hyperthermia in patients with hepatic metastases from ocular melanoma.
Patients underwent treatment on a clinical trial using a 60-min hyperthermic isolated hepatic perfusion (IHP) with melphalan. Microarray analysis was performed in 28 tumor samples obtained intraoperatively of which 12 were pre- and 16 were post-IHP. Various statistical analyses were performed to identify differentially expressed genes and gene categories between the groups.
Median survival of 17 treated patients was 11.9 months. Unsupervised hierarchical clustering of all tumors resulted in separation of pre and post-IHP samples into two distinct groups. Analysis of genes showed that the Ras GTPase activator, ecotropic viral integration site 5 (EVI5), and several other melanoma-associated genes were overexpressed in pre-IHP tumors. In post-IHP samples the overexpression of a DNA replication associated gene, replication factor C (RFC5), was significantly associated with shortened survival (P < 0.003). Other major gene ontology categories identified in the post-IHP tumor samples were DNA-directed RNA polymerase activity and chromatin remodeling, both important categories involved in DNA replication and repair.
These results demonstrate that acute changes in gene expression patterns occur in tumors immediately after treatment with melphalan administered via hyperthermic IHP. Rapid activation of DNA synthesis and repair pathways may be a mechanism of acquired tumor resistance in patients with ocular melanoma.
C1 [Varghese, Sheelu; Alexander, H. Richard, Jr.] Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA.
[Varghese, Sheelu; Alexander, H. Richard, Jr.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Xu, Hui; Bartlett, David; Hughes, Marybeth; Pingpank, James F.; Beresnev, Tatiana] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bartlett, David; Pingpank, James F.] Univ Pittsburgh, Dept Surg, Div Surg Oncol, Med Ctr, Pittsburgh, PA USA.
RP Varghese, S (reprint author), Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA.
EM HRAlexander@smail.umaryland.edu
FU Marlene and Stewart Greenebaum Cancer Center, University of Maryland
School of Medicine, Baltimore, Maryland; Center for Cancer Research,
NCI, Bethesda, Maryland
FX Funding support from the Marlene and Stewart Greenebaum Cancer Center,
University of Maryland School of Medicine, Baltimore, Maryland, and
Center for Cancer Research, NCI, Bethesda, Maryland. The authors thank
Ethan Hagan for technical assistance. Microarray analyses were performed
using BRB ArrayTools 3.6 software package developed by Dr. Richard Simon
of the NCI. The authors have no conflict of interests relevant to this
article to report.
NR 28
TC 10
Z9 10
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2010
VL 17
IS 7
BP 1870
EP 1877
DI 10.1245/s10434-010-0998-z
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 613ZN
UT WOS:000279024200022
PM 20221901
ER
PT J
AU Mosca, M
Tani, C
Aringer, M
Bombardieri, S
Boumpas, D
Brey, R
Cervera, R
Doria, A
Jayne, D
Khamashta, MA
Kuhn, A
Gordon, C
Petri, M
Rekvig, OP
Schneider, M
Sherer, Y
Shoenfeld, Y
Smolen, JS
Talarico, R
Tincani, A
van Vollenhoven, RF
Ward, MM
Werth, VP
Carmona, L
AF Mosca, M.
Tani, C.
Aringer, M.
Bombardieri, S.
Boumpas, D.
Brey, R.
Cervera, R.
Doria, A.
Jayne, D.
Khamashta, M. A.
Kuhn, A.
Gordon, C.
Petri, M.
Rekvig, O. P.
Schneider, M.
Sherer, Y.
Shoenfeld, Y.
Smolen, J. S.
Talarico, R.
Tincani, A.
van Vollenhoven, R. F.
Ward, M. M.
Werth, V. P.
Carmona, L.
TI European League Against Rheumatism recommendations for monitoring
patients with systemic lupus erythematosus in clinical practice and in
observational studies
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Review
ID RISK-FACTORS; ANTIPHOSPHOLIPID ANTIBODIES; DISEASE-ACTIVITY; RENAL
FLARES; CYCLOPHOSPHAMIDE; NEPHRITIS; COHORT; INFECTIONS; PREVALENCE;
WOMEN
AB Objectives To develop recommendations for monitoring patients with systemic lupus erythematosus (SLE) in clinical practice and observational studies and to develop a standardised core set of variables to monitor SLE.
Methods We followed the European League Against Rheumatism (EULAR) standardised procedures for guideline development. The following techniques were applied: nominal groups, Delphi surveys for prioritisation, small group discussion, systematic literature review and two Delphi rounds to obtain agreement. The panel included rheumatologists, internists, dermatologists, a nephrologist and an expert related to national research agencies. The level of evidence and grading of recommendations were determined according to the Levels of Evidence and Grades of Recommendations of the Oxford Centre for Evidence-Based Medicine.
Results A total of 10 recommendations have been developed, covering the following aspects: patient assessment, cardiovascular risk factors, other risk factors (osteoporosis, cancer), infection risk (screening, vaccination, monitoring), frequency of assessments, laboratory tests, mucocutaneous involvement, kidney monitoring, neuropsychological manifestations and ophthalmology assessment. A 'core set' of minimal variables for the assessment and monitoring of patients with SLE in clinical practice was developed that included some of the recommendations. In addition to the recommendations, indications for specific organ assessments that were viewed as part of good clinical practice were discussed and included in the flow chart.
Conclusions A set of recommendations for monitoring patients with SLE in routine clinical practice has been developed. The use of a standardised core set to monitor patients with SLE should facilitate clinical practice, as well as the quality control of care for patients with SLE, and the collection and comparison of data in observational studies.
C1 [Mosca, M.; Tani, C.; Bombardieri, S.; Talarico, R.] Univ Pisa, Rheumatol Unit, Dept Internal Med, I-56126 Pisa, Italy.
[Aringer, M.] Tech Univ Dresden, Univ Clin Ctr Carl Gustav Carus, Dresden, Germany.
[Boumpas, D.] Univ Crete, Sch Med, Iraklion, Greece.
[Brey, R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Neurol, San Antonio, TX 78229 USA.
[Cervera, R.] Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Catalonia, Spain.
[Doria, A.] Univ Padua, Div Rheumatol, Padua, Italy.
[Jayne, D.] Addenbrookes Hosp, Renal Unit, Cambridge, England.
[Khamashta, M. A.] St Thomas Hosp, Rayne Inst, Lupus Res Unit, London SE1 7EH, England.
[Kuhn, A.] Univ Munster, Dept Dermatol, D-4400 Munster, Germany.
[Gordon, C.] Univ Birmingham, Sch Immun & Infect, Birmingham, W Midlands, England.
[Petri, M.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA.
[Rekvig, O. P.] Univ Tromso, Inst Med Biol, Dept Biochem, Fac Med, Tromso, Norway.
[Schneider, M.] Univ Dusseldorf, Clin Endocrinol Diabetol & Rheumatol, Dusseldorf, Germany.
[Sherer, Y.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Hosp Management, IL-69978 Tel Aviv, Israel.
[Shoenfeld, Y.] Chaim Sheba Med Ctr, Dept Med B, IL-52621 Tel Hashomer, Israel.
[Shoenfeld, Y.] Chaim Sheba Med Ctr, Ctr Autoimmune Dis, IL-52621 Tel Hashomer, Israel.
[Shoenfeld, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Smolen, J. S.] Med Univ Vienna, Dept Rheumatol, Vienna, Austria.
[Tincani, A.] Spedali Civil Brescia, UO Reumatol & Immunol Clin, I-25125 Brescia, Italy.
[Tincani, A.] Univ Brescia, Brescia, Italy.
[van Vollenhoven, R. F.] Karolinska Inst, Stockholm, Sweden.
[Ward, M. M.] NIAMSD, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA.
[Carmona, L.] Soc Espanola Reumatol, Res Unit, Madrid, Spain.
RP Mosca, M (reprint author), Univ Pisa, Osped S Chiara, Via Roma 67, I-56126 Pisa, Italy.
EM marta.mosca@int.med.unipi.it
RI Tincani, Angela/E-7608-2010; Carmona, Loreto/A-2748-2014;
OI Carmona, Loreto/0000-0002-4401-2551; Aringer, Martin/0000-0003-4471-8375
FU Intramural NIH HHS [Z99 AR999999]
NR 49
TC 127
Z9 139
U1 2
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUL
PY 2010
VL 69
IS 7
BP 1269
EP 1274
DI 10.1136/ard.2009.117200
PG 6
WC Rheumatology
SC Rheumatology
GA 622MD
UT WOS:000279667000004
PM 19892750
ER
PT J
AU Ryan, JG
Masters, SL
Booty, MG
Habal, N
Alexander, JD
Barham, BK
Remmers, EF
Barron, KS
Kastner, DL
Aksentijevich, I
AF Ryan, J. G.
Masters, S. L.
Booty, M. G.
Habal, N.
Alexander, J. D.
Barham, B. K.
Remmers, E. F.
Barron, K. S.
Kastner, D. L.
Aksentijevich, I.
TI Clinical features and functional significance of the P369S/R408Q variant
in pyrin, the familial Mediterranean fever protein
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID GENE MUTATION; MEFV; AMYLOIDOSIS; ENVIRONMENT; PENETRANCE; FREQUENCY;
DIAGNOSIS; ARTHRITIS; CRITERIA; DISEASES
AB Objectives Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance.
Methods A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions.
Results A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1.
Conclusions P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.
C1 [Ryan, J. G.] NIAMSD, Magnuson Clin Ctr, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA.
[Habal, N.; Barham, B. K.] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Barron, K. S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Ryan, JG (reprint author), NIAMSD, Magnuson Clin Ctr, Genet & Genom Branch, NIH, Bldg 10,10C101C, Bethesda, MD 20892 USA.
EM johngryan@gmail.com
RI Masters, Seth/N-2886-2013;
OI Masters, Seth/0000-0003-4763-576X; Booty, Matthew/0000-0002-0835-3439
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health.
NR 33
TC 35
Z9 35
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUL
PY 2010
VL 69
IS 7
BP 1383
EP 1388
DI 10.1136/ard.2009.113415
PG 6
WC Rheumatology
SC Rheumatology
GA 622MD
UT WOS:000279667000024
PM 19934105
ER
PT J
AU Cho, CS
Kato, GJ
Yang, SH
Bae, SW
Lee, JS
Gladwin, MT
Rhee, SG
AF Cho, Chun-Seok
Kato, Gregory J.
Yang, Seung Ha
Bae, Sung Won
Lee, Jong Seo
Gladwin, Mark T.
Rhee, Sue Goo
TI Hydroxyurea-Induced Expression of Glutathione Peroxidase 1 in Red Blood
Cells of Individuals with Sickle Cell Anemia
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID NITRIC-OXIDE; SUPEROXIDE-DISMUTASE; VASCULAR FUNCTION; FETAL-HEMOGLOBIN;
PEROXIREDOXIN-II; DISEASE; MICE; ERYTHROCYTE; CYSTEINE; ACID
AB Chronic redox imbalance in erythrocytes of individuals with sickle cell disease (SCD) contributes to oxidative stress and likely underlies common etiologies of hemolysis. We measured the amounts of six antioxidant enzymes-SOD1, catalase, glutathione peroxidase 1 (GPx1), as well as peroxiredoxins (Prxs) I, II, and VI-in red blood cells (RBCs) of SCD patients and control subjects. The amounts of SOD1 and Prx VI were reduced by about 17% and 20%, respectively, in SCD RBCs compared with control cells. The amounts of Prx II and GPx1 did not differ between SCD and normal RBCs. However, about 18% of Prx II was inactivated in SCD RBCs as a result of oxidation to sulfinic Prx II, whereas inactive Prx II was virtually undetectable in control cells. Furthermore, GPx1 activity was reduced by about 33% in SCD RBCs, and the loss of activity was correlated with hemolysis in SCD patients. RBCs from SCD patients taking hydroxyurea demonstrated 90% higher GPx1 activity than did those from untreated SCD patients, with no differences seen for the other catalytic antioxidants. Hydroxyurea induced GPx1 expression in multiple cultured cell lines in a manner dependent on both p53 and NO-cGMP signaling pathways. GPx1 expression represents a previously unrecognized potential benefit of hydroxyurea treatment in SCD patients. Antioxid. Redox Signal. 13, 1-11.
C1 [Cho, Chun-Seok; Yang, Seung Ha; Bae, Sung Won; Rhee, Sue Goo] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
[Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Jong Seo] Youngin Ab Frontier Co Ltd, Seoul, South Korea.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
RP Rhee, SG (reprint author), Ewha Womans Univ, Div Life & Pharmaceut Sci, 11-1 Daehyun Dong, Seoul 120750, South Korea.
EM rheesg@ewha.ac.kr
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Korean Science and Engineering Foundation [2006-05106,
M10642040001-07N4204-00110]; Division of Intramural Research of the
National Institutes of Health
FX This study was supported by grants from the Korean Science and
Engineering Foundation (National Honor Scientist Program grant
2006-05106 and Bio R&D program grant M10642040001-07N4204-00110) to S.
G. R. Support was provided to G.J.K. and M. T. W. by the Division of
Intramural Research of the National Institutes of Health. We acknowledge
the contributions of James Nichols and Laurel Mendelsohn for nursing and
technical assistance in specimen procurement and processing. We thank
the patients who provided specimens and data for this study.
NR 51
TC 17
Z9 20
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD JUL
PY 2010
VL 13
IS 1
BP 1
EP 11
DI 10.1089/ars.2009.2978
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 599LT
UT WOS:000277915000001
PM 19951064
ER
PT J
AU Panayiotidis, MI
Franco, R
Bortner, CD
Cidlowski, JA
AF Panayiotidis, Mihalis I.
Franco, Rodrigo
Bortner, Carl D.
Cidlowski, John A.
TI Ouabain-induced perturbations in intracellular ionic homeostasis
regulate death receptor-mediated apoptosis
SO APOPTOSIS
LA English
DT Article
DE Ouabain; Calcium; Na(+)-K(+)-ATPase; Apoptosis; Apoptotic volume
decrease; Fas ligand
ID VASCULAR SMOOTH-MUSCLE; PROGRAMMED CELL-DEATH; PLASMA-MEMBRANE
DEPOLARIZATION; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CULTURED
CORTICAL-NEURONS; SODIUM-PUMP INHIBITION; RATIO BLOCKS APOPTOSIS;
HELIX-ASPERSA NEURONS; PROXIMAL TUBULE CELLS; FAS-INDUCED APOPTOSIS
AB Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na(+)-K(+)-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested to be associated with apoptosis. We report here that the Na(+)-K(+)-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H(2)O(2), thapsigargin or UV-C implicating a role for the Na(+)-K(+)-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca(2+) homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the intracellular Ca(2+) levels in response to H(2)O(2), thapsigargin or UV-C. FasL-induced alterations in Ca(2+) were not abolished in Ca(2+)-free medium but incubation of cells with BAPTA-AM inhibited both Ca(2+) perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the Na(+)-K(+)-ATPase activity during apoptosis is linked to perturbations in cell Ca(2+) homeostasis that modulate apoptosis induced by the activation of Fas by FasL.
C1 [Panayiotidis, Mihalis I.; Franco, Rodrigo; Bortner, Carl D.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, MD F3-07,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM panagiotidism@yahoo.com; rfrancocruz2@unl.edu; cidlows1@niehs.nih.gov
RI Franco, Rodrigo/D-9470-2013;
OI Franco, Rodrigo/0000-0003-3241-8615; Panagiotidis,
Mihalis/0000-0002-1130-5972
FU NIH/ NIEHS
FX We acknowledge Dr. Elizabeth Murphy and Dr. Gary St. J. Bird for the
internal review and comments on this manuscript. We appreciate MS. Maria
Sifre, for technical support in the flow cytometry studies. The research
was supported by the Intramural Research Program of the NIH/ NIEHS.
NR 111
TC 16
Z9 18
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
J9 APOPTOSIS
JI Apoptosis
PD JUL
PY 2010
VL 15
IS 7
BP 834
EP 849
DI 10.1007/s10495-010-0494-8
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 616ED
UT WOS:000279190700008
PM 20422450
ER
PT J
AU Thambisetty, M
Simmons, A
Velayudhan, L
Hye, A
Campbell, J
Zhang, Y
Wahlund, LO
Westman, E
Kinsey, A
Guntert, A
Proitsi, P
Powell, J
Causevic, M
Killick, R
Lunnon, K
Lynham, S
Broadstock, M
Choudhry, F
Howlett, DR
Williams, RJ
Sharp, SI
Mitchelmore, C
Tunnard, C
Leung, R
Foy, C
O'Brien, D
Breen, G
Furney, SJ
Ward, M
Kloszewska, I
Mecocci, P
Soininen, H
Tsolaki, M
Vellas, B
Hodges, A
Murphy, DGM
Parkins, S
Richardson, JC
Resnick, SM
Ferrucci, L
Wong, DF
Zhou, Y
Muehlboeck, S
Evans, A
Francis, PT
Spenger, C
Lovestone, S
AF Thambisetty, Madhav
Simmons, Andrew
Velayudhan, Latha
Hye, Abdul
Campbell, James
Zhang, Yi
Wahlund, Lars-Olof
Westman, Eric
Kinsey, Anna
Guntert, Andreas
Proitsi, Petroula
Powell, John
Causevic, Mirsada
Killick, Richard
Lunnon, Katie
Lynham, Steven
Broadstock, Martin
Choudhry, Fahd
Howlett, David R.
Williams, Robert J.
Sharp, Sally I.
Mitchelmore, Cathy
Tunnard, Catherine
Leung, Rufina
Foy, Catherine
O'Brien, Darragh
Breen, Gerome
Furney, Simon J.
Ward, Malcolm
Kloszewska, Iwona
Mecocci, Patrizia
Soininen, Hilkka
Tsolaki, Magda
Vellas, Bruno
Hodges, Angela
Murphy, Declan G. M.
Parkins, Sue
Richardson, Jill C.
Resnick, Susan M.
Ferrucci, Luigi
Wong, Dean F.
Zhou, Yun
Muehlboeck, Sebastian
Evans, Alan
Francis, Paul T.
Spenger, Christian
Lovestone, Simon
TI Association of Plasma Clusterin Concentration With Severity, Pathology,
and Progression in Alzheimer Disease
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID PHOSPHORYLATED TAU-PROTEIN; GENOME-WIDE ASSOCIATION; REFERENCE TISSUE
MODEL; A-BETA-DEPOSITION; CEREBROSPINAL-FLUID; AMYLOID FORMATION;
IDENTIFIES VARIANTS; SPATIAL CONSTRAINT; APOLIPOPROTEIN-J;
EARLY-DIAGNOSIS
AB Context: Blood-based analytes may be indicators of pathological processes in Alzheimer disease ( AD).
Objective: To identify plasma proteins associated with AD pathology using a combined proteomic and neuro-imaging approach.
Design: Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model.
Setting: A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging.
Participants: Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging.
Main Outcome Measures: Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid.
Results: Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques.
Conclusions: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
C1 [Lovestone, Simon] Kings Coll London, Inst Psychiat, Dept Psychol Med, Dept Old Age Psychiat,Natl Inst Hlth Res Biomed R, London SE5 8AF, England.
[Campbell, James; O'Brien, Darragh; Ward, Malcolm] Proteome Sci, Cobham, England.
[Zhang, Yi; Wahlund, Lars-Olof; Westman, Eric] Karolinska Inst, Karolinska Univ Hosp, Sect Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
[Broadstock, Martin; Choudhry, Fahd; Howlett, David R.; Williams, Robert J.; Sharp, Sally I.; Francis, Paul T.] Kings Coll London, Wolfson Ctr Age Related Disorders, London SE5 8AF, England.
[Mitchelmore, Cathy] Roskilde Univ Ctr, Dept Sci, Eucaryot Cell Biol Res Grp, Roskilde, Denmark.
[Kloszewska, Iwona] Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland.
[Mecocci, Patrizia] Univ Perugia, Dept Clin & Expt Med, Sect Gerontol & Geriatr, I-06100 Perugia, Italy.
[Soininen, Hilkka] Univ Kuopio, Dept Neurol, Kuopio, Finland.
[Soininen, Hilkka] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol, GR-54006 Thessaloniki, Greece.
[Vellas, Bruno] Hop Toulouse, Dept Internal & Geriatr Med, Toulouse, France.
[Richardson, Jill C.] GlaxoSmithKline Inc, Neurosci CEDD, Synapt Plast & Neural Network Dynam DPU, Harlow, Essex, England.
[Resnick, Susan M.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Wong, Dean F.; Zhou, Yun] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Muehlboeck, Sebastian; Evans, Alan] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Spenger, Christian] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
RP Lovestone, S (reprint author), Kings Coll London, Inst Psychiat, Dept Psychol Med, Dept Old Age Psychiat,Natl Inst Hlth Res Biomed R, De Crespigny Pk, London SE5 8AF, England.
EM simon.lovestone@kcl.ac.uk
RI Lovestone, Simon/E-8725-2010; Williams, Robert/A-9180-2008; Simmons,
Andrew/B-8848-2008; Hodges, Angela/C-5676-2011; Furney,
Simon/C-6248-2011; Francis, Paul/A-9199-2008; Powell, John/G-4412-2011;
Sharp, Sally/G-7978-2011; Westman, Eric/H-5771-2011; Breen,
Gerome/A-5540-2010; Lunnon, Katie/C-4638-2012
OI Killick, Richard/0000-0002-8815-3436; Williams,
Robert/0000-0002-2369-1989; Simmons, Andrew/0000-0003-2306-5811; Furney,
Simon/0000-0002-8920-6800; Powell, John/0000-0001-6124-439X; Sharp,
Sally/0000-0003-1363-5219; Breen, Gerome/0000-0003-2053-1792; Lunnon,
Katie/0000-0001-7570-6065
FU European Union; Alzheimer's Research Trust; National Institute for
Health Research (NIHR) Biomedical Research Centre for Mental Health at
the South London; Maudsley National Health Service (NHS) Foundation
Trust; King's College London; Bupa Foundation; Alzheimer's Society;
National Institutes of Health; Acadia; Avid; Bristol-Myers Squibb; GE;
Intracellular; Johnson Johnson; Eli Lilly; Merck; Orexigen; Otsuka;
Roche; Sanofi-Aventis
FX The AddNeuroMed study was funded by the European Union as part of the
FP6 InnoMed program. The authors also received funding from the
Alzheimer's Research Trust, the National Institute for Health Research
(NIHR) Biomedical Research Centre for Mental Health at the South London
and Maudsley National Health Service (NHS) Foundation Trust and King's
College London, the Bupa Foundation, and the Alzheimer's Society
(fellowship to Dr Thambisetty).; Financial Disclosure: Intellectual
property has been registered on the use of plasma proteins, including
clusterin, for use as biomarkers for AD by King's College London and
Proteome Sciences, with Drs Lovestone and Thambisetty and others named
as inventors. Dr Wong has grant support and/or contracts from the
National Institutes of Health, Acadia, Avid, Bristol-Myers Squibb, GE,
Intracellular, Johnson & Johnson, Eli Lilly, Merck, Orexigen, Otsuka,
Roche, and Sanofi-Aventis.
NR 47
TC 182
Z9 186
U1 0
U2 22
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JUL
PY 2010
VL 67
IS 7
BP 739
EP 748
PG 10
WC Psychiatry
SC Psychiatry
GA 620RU
UT WOS:000279517800010
PM 20603455
ER
PT J
AU Jayasundera, T
Branham, KEH
Othman, M
Rhoades, WR
Karoukis, AJ
Khanna, H
Swaroop, A
Heckenlively, JR
AF Jayasundera, Thiran
Branham, Kari E. H.
Othman, Mohammad
Rhoades, William R.
Karoukis, Athanasios J.
Khanna, Hemant
Swaroop, Anand
Heckenlively, John R.
TI RP2 Phenotype and Pathogenetic Correlations in X-Linked Retinitis
Pigmentosa
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID NORTH-AMERICAN COHORT; LINKAGE ANALYSIS; PLASMA-MEMBRANE; RPGR
MUTATIONS; PROTEIN RP2; FAMILIES; GENE; IDENTIFICATION
AB Objectives: To assess the phenotype of patients with X-linked retinitis pigmentosa (XLRP) with RP2 mutations and to correlate the findings with their genotype.
Methods: Six hundred eleven patients with RP were screened for RP2 mutations. From this screen, 18 patients with RP2 mutations were evaluated clinically with standardized electroretinography, Goldmann visual fields, and ocular examinations. In addition, 7 well-documented cases from the literature were used to augment genotype-phenotype correlations.
Results: Of 11 boys younger than 12 years, 10 (91%) had macular involvement and 9 (82%) had best-corrected visual acuity worse than 20/50. Two boys from different families (aged 8 and 12 years) displayed a choroideremia-like fundus, and 9 boys (82%) were myopic (mean error, -7.97 diopters [D]). Of 10 patients with electroretinography data, 9 demonstrated severe rod-cone dys-function. All 3 female carriers had macular atrophy in 1 or both eyes and were myopic (mean, 6.23 D). All 9 nonsense and frameshift and 5 of 7 missense mutations (71%) resulted in severe clinical presentations.
Conclusions: Screening of the RP2 gene should be prioritized in patients younger than 16 years characterized by X-linked inheritance, decreased best-corrected visual acuity (eg, >20/40), high myopia, and early-onset macular atrophy. Patients exhibiting a choroideremia-like fundus without choroideremia gene mutations should also be screened for RP2 mutations.
Clinical Relevance: An identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.
C1 [Jayasundera, Thiran; Branham, Kari E. H.; Othman, Mohammad; Rhoades, William R.; Karoukis, Athanasios J.; Khanna, Hemant; Swaroop, Anand; Heckenlively, John R.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA.
[Swaroop, Anand] NIH, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
RP Heckenlively, JR (reprint author), Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM jrheck@umich.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU Foundation Fighting Blindness; National Eye Institute Intramural
Research Program; National Eye Institute [R01 EY007961]
FX This research was supported by grants from the Foundation Fighting
Blindness and the National Eye Institute Intramural Research Program (Dr
Swaroop) and by grant R01 EY007961 from the National Eye Institute.
NR 35
TC 25
Z9 25
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUL
PY 2010
VL 128
IS 7
BP 915
EP 923
PG 9
WC Ophthalmology
SC Ophthalmology
GA 625DB
UT WOS:000279871900019
PM 20625056
ER
PT J
AU Hammond, MEH
Hayes, DF
Dowsett, M
Allred, DC
Hagerty, KL
Badve, S
Fitzgibbons, PL
Francis, G
Goldstein, NS
Hayes, M
Hicks, DG
Lester, S
Love, R
Mangu, PB
McShane, L
Miller, K
Osborne, CK
Paik, S
Perlmutter, J
Rhodes, A
Sasano, H
Schwartz, JN
Sweep, FCG
Taube, S
Torlakovic, EE
Valenstein, P
Viale, G
Visscher, D
Wheeler, T
Williams, RB
Wittliff, JL
Wolff, AC
AF Hammond, M. Elizabeth H.
Hayes, Daniel F.
Dowsett, Mitch
Allred, D. Craig
Hagerty, Karen L.
Badve, Sunil
Fitzgibbons, Patrick L.
Francis, Glenn
Goldstein, Neil S.
Hayes, Malcolm
Hicks, David G.
Lester, Susan
Love, Richard
Mangu, Pamela B.
McShane, Lisa
Miller, Keith
Osborne, C. Kent
Paik, Soonmyung
Perlmutter, Jane
Rhodes, Anthony
Sasano, Hironobu
Schwartz, Jared N.
Sweep, Fred C. G.
Taube, Sheila
Torlakovic, Emina Emilia
Valenstein, Paul
Viale, Giuseppe
Visscher, Daniel
Wheeler, Thomas
Williams, R. Bruce
Wittliff, James L.
Wolff, Antonio C.
TI American Society of Clinical Oncology/College of American Pathologists
Guideline Recommendations for Immunohistochemical Testing of Estrogen
and Progesterone Receptors in Breast Cancer (Unabridged Version)
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID CENTRALLY REVIEWED EXPRESSION; TAMOXIFEN ADJUVANT THERAPY; RABBIT
MONOCLONAL-ANTIBODY; LIGAND-BINDING ASSAY; PREDICTING RESPONSE; FORMALIN
FIXATION; ENDOCRINE THERAPY; HORMONAL-THERAPY; PREMENOPAUSAL VIETNAMESE;
AROMATASE INHIBITORS
AB Purpose.-To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.
Methods.-The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.
Results.-Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria.
Recommendations.-The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials. (Arch Pathol Lab Med. 2010;134:e48-e72)
C1 [Hammond, M. Elizabeth H.] ASCO, Canc Policy & Clin Affairs, Alexandria, VA 22314 USA.
Univ Utah, Sch Med, Salt Lake City, UT USA.
Washington Univ, Sch Med, St Louis, MO USA.
Univ Michigan, Ctr Comprehens Canc, Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA.
St Joseph Mercy Hosp, Gemini Grp, Ann Arbor, MI 48104 USA.
Adv Diagnost Lab, Redford, MI USA.
Presbyterian Hosp, Charlotte, NC USA.
Indiana Univ, Bloomington, IN USA.
St Jude Med Ctr, Fullerton, CA USA.
Univ Rochester, Rochester, NY USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NCI, Bethesda, MD 20892 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Ohio State Univ, Columbus, OH 43210 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Delta Pathol Grp, Shreveport, LA USA.
Univ Louisville, Louisville, KY 40292 USA.
Royal Marsden Hosp, London SW3 6JJ, England.
Natl External Qual Assessment Serv, Sheffield, S Yorkshire, England.
Univ W England, Bristol BS16 1QY, Avon, England.
Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada.
Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan.
Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands.
European Inst Oncol, Milan, Italy.
Univ Milan, Milan, Italy.
RP Hammond, MEH (reprint author), ASCO, Canc Policy & Clin Affairs, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
RI Sweep, C.G.J./H-8096-2014; Rhodes, Anthony/O-9062-2014; Wolff,
A.P./L-4767-2015
OI Rhodes, Anthony/0000-0002-1187-0939;
NR 93
TC 280
Z9 298
U1 4
U2 16
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUL
PY 2010
VL 134
IS 7
BP E48
EP E72
PG 25
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 622BQ
UT WOS:000279633900001
PM 20586616
ER
PT J
AU Drinkard, BE
Keyser, RE
Paul, SM
Arena, R
Plehn, JF
Yanovski, JA
Di Prospero, NA
AF Drinkard, Bart E.
Keyser, Randall E.
Paul, Scott M.
Arena, Ross
Plehn, Jonathan F.
Yanovski, Jack A.
Di Prospero, Nicholas A.
TI Exercise Capacity and Idebenone Intervention in Children and Adolescents
With Friedreich Ataxia
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Exercise; Friedreich Ataxia; Idebenone [substance name]; Rehabilitation
ID HIGH-DOSE IDEBENONE; IMPEDANCE CARDIOGRAPH DEVICE; PLACEBO-CONTROLLED
TRIAL; CARDIAC-OUTPUT; IN-VIVO; THORACIC BIOIMPEDANCE; HEALTHY-CHILDREN;
HEART-FAILURE; RATING-SCALE; HYPERTROPHY
AB Drinkard BE, Keyser RE, Paul SM, Arena R, Plehn JF, Yanovski JA, Di Prospero NA. Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia. Arch Phys Med Rehabil 2010;91:1044-50.
Objective: To determine the exercise capacity of children and adolescents with Friedreich's Ataxia (FA) and to evaluate the effects of 6 months of idebenone treatment on exercise capacity.
Design: Exploratory endpoint in a randomized double-blind, placebo-controlled, phase II clinical trial designed to investigate the effects of idebenone on a biomarker of oxidative stress.
Setting: Exercise physiology laboratory in a single clinical research center.
Participants: Ambulatory subjects (N=48; age range, 9-17y) with genetically confirmed FA.
Intervention: Idebenone administered orally 3 times a day for a total daily dose of approximately 5, 15, and 45mg/kg or matching placebo for 6 months.
Main Outcome Measures: Peak oxygen consumption per unit time (peak VO(2)) and peak work rate (WR) were measured during incremental exercise testing at baseline and after treatment. Echocardiography and neurologic assessments were also completed before and after treatment.
Results: Baseline mean peak VO(2) SD was 746 +/- 246mL/min (16.2 +/- 5.8mL/kg/min), and WR was 40 +/- 23W for all subjects. Peak VO(2) and WR were correlated with short guanine-adenine-adenine allele length and neurologic function. Relative left ventricular wall thickness was increased but left ventricular ejection fraction was normal in most subjects; there was no relationship between any exercise and echocardiographic measures. There were no significant changes in mean peak VO(2) or WR after idebenone treatment at any dose level relative to placebo.
Conclusions: Exercise capacity in children and adolescents with FA was significantly impaired. The basis for the impairment appears to be multifactorial and correlated to the degree of neurologic impairment. Although idebenone has previously been shown potentially to improve features of FA, idebenone treatment did not increase exercise capacity relative to placebo.
C1 [Drinkard, Bart E.; Keyser, Randall E.; Paul, Scott M.] NIH, Dept Rehabil Med, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Plehn, Jonathan F.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Yanovski, Jack A.] NICHHD, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA.
[Di Prospero, Nicholas A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Keyser, Randall E.] George Mason Univ, Ctr Study Chron Illness & Disabil, Fairfax, VA 22030 USA.
[Arena, Ross] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
[Arena, Ross] Virginia Commonwealth Univ, Dept Physiol, Richmond, VA USA.
[Arena, Ross] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA.
RP Drinkard, BE (reprint author), NIH, Dept Rehabil Med, Hatfield Clin Res Ctr, Bldg 10,Room 1-1469,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Bart_Drinkard@nih.gov
RI Arena, Ross/A-3141-2008;
OI Arena, Ross/0000-0002-6675-1996; Paul, Scott/0000-0003-1274-6670;
Yanovski, Jack/0000-0001-8542-1637
FU National Institutes of Health/National Institute of Neurological
Disorders and Stroke/National Heart, Lung, and Blood Institute
FX Supported by the National Institutes of Health/National Institute of
Neurological Disorders and Stroke/National Heart, Lung, and Blood
Institute intramural research funds.
NR 45
TC 13
Z9 13
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUL
PY 2010
VL 91
IS 7
BP 1044
EP 1050
DI 10.1016/j.apmr.2010.04.007
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 625PM
UT WOS:000279907400006
PM 20599042
ER
PT J
AU Hong, JJ
Schrump, DS
Hughes, MS
AF Hong, Jenny J.
Schrump, David S.
Hughes, Marybeth S.
TI Image of the Month Cystic Parathyroid Adenoma
SO ARCHIVES OF SURGERY
LA English
DT Editorial Material
C1 [Hughes, Marybeth S.] NCI, Surg Branch, NIH, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Hughes, MS (reprint author), NCI, Surg Branch, NIH, Hatfield Clin Res Ctr, CRC Bldg 10,Room 4W-5940, Bethesda, MD 20892 USA.
EM hughesm@mail.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD JUL
PY 2010
VL 145
IS 7
BP 705
EP 706
PG 2
WC Surgery
SC Surgery
GA 626VA
UT WOS:000279994200016
PM 20644137
ER
PT J
AU Lam, CSP
Chen, MH
Lacey, SM
Yang, QO
Sullivan, LM
Xanthakis, V
Safa, R
Smith, HM
Peng, XY
Sawyer, DB
Vasan, RS
AF Lam, Carolyn S. P.
Chen, Ming-Huei
Lacey, Sean M.
Yang, Qiong
Sullivan, Lisa M.
Xanthakis, Vanessa
Safa, Radwan
Smith, Holly M.
Peng, Xuyang
Sawyer, Douglas B.
Vasan, Ramachandran S.
TI Circulating Insulin-Like Growth Factor-1 and Its Binding Protein-3
Metabolic and Genetic Correlates in the Community
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE epidemiology; growth factors; insulin resistance; risk factors
ID FACTOR BINDING-PROTEIN-3 CONCENTRATIONS; IMPROVES GLYCEMIC CONTROL;
IGF-I; BLOOD-PRESSURE; LIFE-STYLE; ESSENTIAL-HYPERTENSION;
GLUCOSE-HOMEOSTASIS; RANCHO-BERNARDO; SERUM; AGE
AB Objective-The metabolic and genetic correlates of circulating insulin-like growth factor-1 (IGF-1) and its main circulating carrier, IGF-1-binding-protein-3 (IGFBP-3), are unclear.
Methods and Results-We measured serum IGF-1 and IGFBP-3 concentrations in a sample of the Framingham Heart Study (N=3977, aged 40 +/- 9 years, 46% male) and evaluated their relations to cardiovascular risk factors using multivariable regression. Serum IGF-1 was inversely correlated with age, body mass index, total cholesterol, the presence of diabetes, alcohol consumption, and glomerular filtration rate (all P<0.01), whereas the ratio of IGF-1: IGFBP-3 was lower in women and inversely related to age, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, and alcohol consumption (all P<0.0001). Circulating IGF-1 correlated negatively with insulin resistance (homeostatic model assessment) (r=-0.1; P<0.0001) and was lower in participants with more components of the metabolic syndrome (Adult Treatment Panel III criteria) (P<0.0001). Additive genetic factors (heritability) accounted for 43% and 39% of the variation of IGF-1 and IGFBP-3, respectively (both P<10(-27)).
Conclusion-Our cross-sectional observations in a large community-based sample link lower circulating IGF-1 to greater metabolic risk burden and underscore substantial genetic influences on IGF-1 concentrations. Prospective studies are warranted to elucidate whether lower IGF-1 concentrations predict greater metabolic risk longitudinally. (Arterioscler Thromb Vasc Biol. 2010; 30: 1479-1484.)
C1 [Lam, Carolyn S. P.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Lacey, Sean M.; Yang, Qiong; Sullivan, Lisa M.; Xanthakis, Vanessa] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA.
[Smith, Holly M.; Peng, Xuyang; Sawyer, Douglas B.] Vanderbilt Univ, Nashville, TN USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM vasan@bu.edu
RI Yang, Qiong/G-5438-2014;
OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan,
Lisa/0000-0003-0726-7149
FU National Heart, Lung and Blood Institute [N01-HC-25195]; NIH
[R01-HL-077477]
FX This work was supported by the National Heart, Lung and Blood Institute
(contract N01-HC-25195) and NIH grant R01-HL-077477 (to R. S. V.).
NR 50
TC 28
Z9 31
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2010
VL 30
IS 7
BP 1479
EP U513
DI 10.1161/ATVBAHA.110.203943
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 611WW
UT WOS:000278856600028
PM 20378848
ER
PT J
AU Vosters, JL
Landek-Salgado, MA
Kimura, H
Tak, PP
Caturegli, P
Yin, H
Swaim, WD
Chiorini, JA
AF Vosters, Jelle L.
Landek-Salgado, Melissa A.
Kimura, Hiroaki
Tak, Paul P.
Caturegli, Patrizio
Yin, Hongen
Swaim, William D.
Chiorini, John A.
TI The enigmatic role of interleukin-12 in the pathogenesis of Sjogren's
syndrome: comment on the article by Vosters et al Reply
SO ARTHRITIS AND RHEUMATISM
LA English
DT Letter
ID TRANSGENIC MICE
C1 [Vosters, Jelle L.; Yin, Hongen; Swaim, William D.] NIH, Bethesda, MD 20892 USA.
[Vosters, Jelle L.; Tak, Paul P.] Univ Amsterdam, Amsterdam, Netherlands.
[Landek-Salgado, Melissa A.; Kimura, Hiroaki; Caturegli, Patrizio] Johns Hopkins Sch Med, Baltimore, MD USA.
[Caturegli, Patrizio] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
RP Vosters, JL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUL
PY 2010
VL 62
IS 7
BP 2180
EP 2181
DI 10.1002/art.27482
PG 2
WC Rheumatology
SC Rheumatology
GA 661VM
UT WOS:000282758500041
ER
PT J
AU Neufeld, EB
Yu, ZX
Springer, D
Yu, Q
Balaban, RS
AF Neufeld, Edward B.
Yu, Zu-Xi
Springer, Danielle
Yu, Qing
Balaban, Robert S.
TI The renal artery ostium flow diverter: Structure and potential role in
atherosclerosis
SO ATHEROSCLEROSIS
LA English
DT Article
DE Renal artery ostium; Collagen; Elastin; LDL retention; Two-photon
microscopy; Doppler ultrasound; Atherosclerosis
ID BLOOD VELOCITY PROFILES; LOW-DENSITY-LIPOPROTEIN; LESIONS;
PROTEOGLYCANS; STENOSIS; CHILDREN; IDENTIFICATION; ASSOCIATION
AB Initiation of renal atherosclerosis occurs primarily at the caudal region of the renal artery ostium. To date, no mechanism for initiation of atherosclerosis at this site has been substantiated. Herein, we identify a renal artery flow diverter on the caudal wall of the renal artery ostium that directs flow into the renal artery and selectively retains LDL, an initial step in atherosclerosis. High-resolution ultrasound revealed the generation of flow eddies by the caudal diverter in vivo, consistent with a role in directing aortic flow to the renal artery. Two-photon excitation en face microscopy of the diverter revealed a substantial reduction in the elastic lamina exposing potential retention sites for LDL. Fluorescent LDL was selectively retained by the renal artery diverter, consistent with its molecular structure. We propose that the rigid macromolecular structure of the renal artery ostium diverter is required for its vascular function and contributes to the initiation of renal atherosclerosis by the retention of LDL. Published by Elsevier Ireland Ltd.
C1 [Neufeld, Edward B.; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Yu, Qing] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Neufeld, EB (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM neufelde@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 20
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2010
VL 211
IS 1
BP 153
EP 158
DI 10.1016/j.atherosclerosis.2010.01.024
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 620VV
UT WOS:000279530000029
PM 20149375
ER
PT J
AU Zhou, W
Chen, KH
Cao, WJ
Zeng, JW
Liao, H
Zhao, L
Guo, XM
AF Zhou, Wei
Chen, Kuang-Hueih
Cao, Wenjing
Zeng, Jingwei
Liao, Hua
Zhao, Li
Guo, Xiaomei
TI Mutation of the protein kinase A phosphorylation site influences the
anti-proliferative activity of mitofusin 2
SO ATHEROSCLEROSIS
LA English
DT Article
DE Mitofusin 2; Mutation; Vascular smooth muscle cells; Proliferation;
Neointimal hyperplasia
ID MUSCLE-CELL PROLIFERATION; MITOCHONDRIAL FUSION; SKELETAL-MUSCLE;
EXPRESSION; DEATH; OVEREXPRESSION; ACTIVATION; APOPTOSIS; OBESITY; P53
AB Objective: Mitofusin 2 (Mfn2) is an important suppressor of vascular smooth muscle cell (VSMC) proliferation. It contains a protein kinase A (PKA) phosphorylation site at serine 442 (S442) and can be phosphorylated by PKA. This study examined the role of phosphorylating specific sites on the regulation of Mfn2 protein activity in vitro and in vivo.
Methods and results: We introduced two mutations at S442 in rat Mfn2, and investigated their effects using cultured rat VSMCs and the balloon injury model. Our results indicated that, in VSMCs, Mfn2 expression and mitochondrial morphology are affected by adenoviral-mediated overexpression of the two Mfn2 mutant proteins in the same way as the wild-type Mfn2 protein. Specifically, overexpression of the protein harboring the phospho-deficient mutation Mfn2-S442A (serine replaced by alanine at residue 442) increased the inhibitory effects of Mfn2 on proliferation of VSMCs in culture, and neointimal hyperplasia and restenosis in the rat carotid artery balloon injury model at days 14 after injury. On the other hand, the phospho-mimetic mutation Mfn2-S442D (serine replaced by aspartic acid at residue 442) led to loss of growth suppressor activity.
Conclusions: These results suggest that this specific PKA phosphorylation site plays a key role in Mfn2-mediated suppression of VSMC growth, which is independent of its effects on modulation of mitochondrial morphology. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Zhou, Wei; Zeng, Jingwei; Liao, Hua; Zhao, Li; Guo, Xiaomei] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Cardiol, Tongji Med Coll, Wuhan 430030, Peoples R China.
[Chen, Kuang-Hueih] NIA, Immunol Lab, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Cao, Wenjing] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Clin Lab, Wuhan 430030, Peoples R China.
RP Guo, XM (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Dept Cardiol, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM xmguo59@gmail.com
FU National Natural Science Foundation, China [30672206, 30600233]
FX This study was supported by China grants from the National Natural
Science Foundation (grant numbers: 30672206 and 30600233).
NR 30
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U1 0
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2010
VL 211
IS 1
BP 216
EP 223
DI 10.1016/j.atherosclerosis.2010.02.012
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 620VV
UT WOS:000279530000040
PM 20303493
ER
PT J
AU Aboyans, V
Kamineni, A
Allison, MA
McDermott, MM
Crouse, JR
Ni, HY
Szklo, M
Criqui, MH
AF Aboyans, Victor
Kamineni, Aruna
Allison, Matthew A.
McDermott, Mary McGrae
Crouse, John R.
Ni, Hanyu
Szklo, Moyses
Criqui, Michael H.
TI The epidemiology of subclavian stenosis and its association with markers
of subclinical atherosclerosis: The Multi-Ethnic Study of
Atherosclerosis (MESA)
SO ATHEROSCLEROSIS
LA English
DT Article
DE Subclavian artery; Blood pressure; Atherosclerosis; Epidemiology
ID PERIPHERAL ARTERIAL-DISEASE; BLOOD-PRESSURE-MEASUREMENTS; ANKLE-BRACHIAL
INDEX; CARDIOVASCULAR RISK; PRIMARY-CARE; POPULATION; PREVALENCE;
DIFFERENCE; SURGERY; EQUATIONS
AB Background: Recent studies indicate that subclavian stenosis (SS), diagnosed by a large systolic blood pressure difference (SBPD) between the right and left brachial arteries, is associated with cardiovascular disease (CVD) risk factors and outcomes. We sought to describe the epidemiology of SS and determine its association with markers of subclinical CVD in the baseline cohort of the Multi-Ethnic Study of Atherosclerosis.
Methods: We defined SS by an absolute SBPD >= 15 mmHg. Peripheral artery disease (PAD) was defined by an ankle-brachial index <= 0.90. The coronary artery calcium score (CAC) and the common carotid artery intima-media thickness (CCA-IMT) were measured by computed tomography and B-mode ultrasound, respectively. Odds ratios for the associations of SS with risk factors and subclinical disease were estimated using logistic regression.
Results: Of 6743 subjects studied, 307 participants (4.6%) had SS, with a higher prevalence in women(5.1%) than men (3.9%), and in African Americans (7.4%) and non-Hispanic whites (5.1%) than Hispanic (1.9%) or Chinese (1.0%) participants (p < 0.01). In a model including age, gender, ethnicity, traditional and novel CVD risk factors, significant associations with SS were observed for C-reactive protein (highest vs. three lower quartiles: OR = 1.41; 95% CI: 1.06-1.87) and brachial artery pulse pressure (OR = 1.12/10 mmHg; 95% CI: 1.03-1.21). Adjusted for age, gender, ethnicity, traditional and novel CVD risk factors, SS was significantly associated with PAD(OR = 2.35; 1.55-3.56), with CCA-IMT (highest vs. the lower three quartiles: OR = 1.32; 1.00-1.75), and high CAC (score > 100 vs. score = 0; OR = 1.43; 1.03-2.01).
Conclusions: The subclavian stenosis is positively associated with other markers of subclinical atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Aboyans, Victor] Dupuytren Univ Hosp, Dept Thorac & Cardiovasc Surg & Vasc Med, F-87042 Limoges, France.
[Aboyans, Victor; Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Aboyans, Victor] Univ Limoges, EA3174, Limoges, France.
[Kamineni, Aruna] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[McDermott, Mary McGrae] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Crouse, John R.] Wake Forest Univ Hlth Sci, Dept Internal Med Endocrinol, Winston Salem, NC USA.
[Ni, Hanyu] NHLBI, Bethesda, MD 20892 USA.
[Szklo, Moyses] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Criqui, Michael H.] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
RP Aboyans, V (reprint author), Dupuytren Univ Hosp, Dept Thorac & Cardiovasc Surg & Vasc Med, 2 Ave Martin Luther King, F-87042 Limoges, France.
EM vaboyans@ucsd.edu
OI Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165,
N01-HC-95169]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood
Institute. The authors thank the other investigators, the staff, and the
participants of the MESA study for their valuable contributions. A full
list of participating MESA investigators and institutions can be found
at http://www.mesa-nhlbi.org.
NR 30
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U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2010
VL 211
IS 1
BP 266
EP 270
DI 10.1016/j.atherosclerosis.2010.01.013
PG 5
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 620VV
UT WOS:000279530000048
PM 20138280
ER
PT J
AU Alevizos, I
Illei, GG
AF Alevizos, Ilias
Illei, Gabor G.
TI MicroRNAs in Sjogren's syndrome as a prototypic autoimmune disease
SO AUTOIMMUNITY REVIEWS
LA English
DT Review
DE Biomarker; Autoimmunity; Epigenetics; Exocrine dysfunction; Pathogenesis
ID FIBROBLAST-LIKE SYNOVIOCYTES; RHEUMATOID-ARTHRITIS; IMMUNE-SYSTEM;
EXPRESSION; CELLS; LUPUS; PATHOGENESIS; MECHANISM; EXOSOME; TISSUE
AB MicroRNAs are endogenous non-coding RNAs, approximately 22 nucleotides in length They regulate gene expression and are important in a wide range of physiological and pathological processes MicroRNA expression is tightly regulated during hematopoiesis and lymphoid cell differentiation and disruption of the entire microRNA network or selected microRNAs may lead to dysregulated immune responses Abnormalities in microRNA expression related to inflammatory cytokines. Th-17 and regulatory T cells as well as B cells have been described in several autoimmune diseases Sjogren's syndrome is characterized by features of systemic autoimmunity and chronic inflammation and dysfunction in exocrine organs Its clinical characteristics along with the relatively easy access to the target tissue and its product makes Sjogren's syndrome appealing to study many aspects of microRNAs in a systemic autoimmune disease, such as their potential as diagnostic or prognostic biomarkers and their role in pathogenesis of autoimmunity, inflammation or organ dysfunction Encouraging preliminary data from pilot studies in Sjogren's syndrome demonstrate the potential of microRNAs as putative diagnostic and prognostic biomarker candidates which should be tested in larger more definite studies. Combining the comparison of microRNA expression profiles between various clinical subsets of Sjogren's syndrome with bioinformatic modeling tools may predict formerly unsuspected pathways which may contribute to the disease process and lead to the generation of testable novel hypothesis of pathogenesis. Published by Elsevier B V.
C1 [Alevizos, Ilias; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, Bethesda, MD USA.
RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, Bethesda, MD USA.
FU Intramural NIH HHS [ZIA DE000704-10]
NR 34
TC 37
Z9 38
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9972
J9 AUTOIMMUN REV
JI Autoimmun. Rev.
PD JUL
PY 2010
VL 9
IS 9
SI SI
BP 618
EP 621
DI 10.1016/j.autrev.2010.05.009
PG 4
WC Immunology
SC Immunology
GA 632YI
UT WOS:000280465400008
PM 20457282
ER
PT J
AU Lu, QJ
Renaudineau, Y
Cha, S
Ilei, G
Brooks, WH
Selmi, C
Tzioufas, A
Pers, JO
Bombardieri, S
Gershwin, ME
Gay, S
Youinou, P
AF Lu, Qianjin
Renaudineau, Yves
Cha, Seunghee
Ilei, Gabor
Brooks, Wesley H.
Selmi, Carlo
Tzioufas, Athanasios
Pers, Jacques-Olivier
Bombardieri, Stefano
Gershwin, M. Eric
Gay, Steffen
Youinou, Pierre
TI Epigenetics in autoimmune disorders: Highlights of the 10th Sjogren's
Syndrome Symposium
SO AUTOIMMUNITY REVIEWS
LA English
DT Review
DE Epigenetics; Sjogren's syndrome; Rheumatoid arthritis; Autoimmune
diseases
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DNA METHYLATION; RHEUMATOID-ARTHRITIS;
SYNOVIAL TISSUE; EXPRESSION; CELLS; FIBROBLASTS; MICRORNAS; PATHWAY;
GENES
AB During the 10th International Symposium on Sjogren's Syndrome held in Brest. France, from October 1-3, 2009 (http //www sjogrensymposium-brest2009 org). the creation of an international epigenetic autoimmune group has been proposed to establish gold standards and to launch collaborative studies During this "epigenetics session", leading experts in the field presented and discussed the most recent developments of this topic in Sjogren's Syndrome research The "Brest epigenetic task force" was born and has scheduled a meeting in Ljubljana, Slovenia during the 7th Autoimmunity congress in May 2010 The following is a report of that session (C) 2010 Elsevier B.V All rights reserved
C1 [Lu, Qianjin] Epigenet Res Ctr, Dept Dermatol, Changsha, Hunan, Peoples R China.
[Renaudineau, Yves; Pers, Jacques-Olivier; Youinou, Pierre] Univ Brest, Immunol Lab, Brest, France.
[Cha, Seunghee] Univ Florida, Dept Oral & Maxillofacial Surg, Gainesville, FL 32611 USA.
[Ilei, Gabor] NIH, Sjogrens Syndrome Clin, Bethesda, MD 20892 USA.
[Brooks, Wesley H.] Moffitt Res Inst, Expt HTS, Tampa, FL USA.
[Selmi, Carlo] Univ Milan, IRCCS Ist Clin Humanitas, I-20122 Milan, Italy.
[Tzioufas, Athanasios] Univ Athens, Dept Pathophysiol, GR-10679 Athens, Greece.
[Bombardieri, Stefano] Univ Pisa, Rheumatol Unit, I-56100 Pisa, Italy.
[Gay, Steffen] Univ Zurich, Dept Rheumatol, CH-8006 Zurich, Switzerland.
RP Youinou, P (reprint author), Brest Univ Med Sch Hosp, Immunol Lab, BP 824, F-29609 Brest, France.
OI Renaudineau, Yves/0000-0001-5098-5002
FU NIDCR NIH HHS [R01 DE019644]
NR 29
TC 29
Z9 30
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9972
J9 AUTOIMMUN REV
JI Autoimmun. Rev.
PD JUL
PY 2010
VL 9
IS 9
SI SI
BP 627
EP 630
DI 10.1016/j.autrev.2010.05.011
PG 4
WC Immunology
SC Immunology
GA 632YI
UT WOS:000280465400010
PM 20452464
ER
PT J
AU Strunk, DR
Brotman, MA
DeRubeis, RJ
AF Strunk, Daniel R.
Brotman, Melissa A.
DeRubeis, Robert J.
TI The process of change in cognitive therapy for depression: Predictors of
early inter-session symptom gains
SO BEHAVIOUR RESEARCH AND THERAPY
LA English
DT Article
DE Cognitive therapy; Depression; Adherence; Therapeutic alliance; Patient
ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT;
BEHAVIOR-THERAPY; SUDDEN GAINS; PSYCHOTHERAPY PROCESS; NATIONAL
INSTITUTE; WORKING ALLIANCE; RATING-SCALE; MEDICATIONS; ADHERENCE
AB Although cognitive therapy for depression is an efficacious treatment, questions about the aspects of the therapy that are most critical to successful implementation remain. In a sample of 60 cognitive therapy patients with moderate to severe depression, we examined three aspects of therapists' adherence to cognitive therapy techniques, the patients' facilitation or inhibition of these techniques, and the therapeutic alliance as predictors of session-to-session symptom improvement across the first five therapy sessions. Two elements of therapist adherence (viz., cognitive methods and negotiating content/structuring sessions) emerged as the strongest predictors of symptom improvement. Patient facilitation or inhibition of therapist adherence also predicted subsequent symptom change. Neither adherence to behavioral methods/homework nor the therapeutic alliance was a significant predictor in parallel analyses. Although alliance scores did not predict subsequent symptom change, they were significantly predicted by prior symptom change. These findings support the model of change that motivates cognitive therapy for depression, and they highlight the potential role of patient facilitation of therapists' adherence in treatment response. Published by Elsevier Ltd.
C1 [Strunk, Daniel R.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Brotman, Melissa A.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[DeRubeis, Robert J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA.
RP Strunk, DR (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA.
EM strunk.20@osu.edu
RI Brotman, Melissa/H-7409-2013; Strunk, Daniel/F-4153-2011
OI Strunk, Daniel/0000-0002-7444-0741
FU NIMH NIH HHS [R10 MH055875-05, R10 MH055877, R10 MH055877-05]
NR 49
TC 54
Z9 54
U1 3
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0005-7967
J9 BEHAV RES THER
JI Behav. Res. Ther.
PD JUL
PY 2010
VL 48
IS 7
BP 599
EP 606
DI 10.1016/j.brat.2010.03.011
PG 8
WC Psychology, Clinical
SC Psychology
GA 614FW
UT WOS:000279041800004
PM 20362978
ER
PT J
AU Salat, J
Paesen, GC
Rezacova, P
Kotsyfakis, M
Kovarova, Z
Sanda, M
Majtan, J
Grunclova, L
Horka, H
Andersen, JF
Brynda, J
Horn, M
Nunn, MA
Kopacek, P
Kopecky, J
Mares, M
AF Salat, Jiri
Paesen, Guido C.
Rezacova, Pavlina
Kotsyfakis, Michalis
Kovarova, Zuzana
Sanda, Miloslav
Majtan, Juraj
Grunclova, Lenka
Horka, Helena
Andersen, John F.
Brynda, Jiri
Horn, Martin
Nunn, Miles A.
Kopacek, Petr
Kopecky, Jan
Mares, Michael
TI Crystal structure and functional characterization of an immunomodulatory
salivary cystatin from the soft tick Ornithodoros moubata
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE cathepsin; cystatin; Ornithodoros moubata; parasite; peptidase inhibitor
ID DIPEPTIDYL PEPTIDASE-I; IXODES-SCAPULARIS; ANTIGEN PRESENTATION;
SIALOSTATIN-L; INHIBITION; PROTEASES; PROTEIN; MODEL; SPECIFICITY;
REFINEMENT
AB The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 angstrom (1 angstrom = 0.1 nm) and was used to describe the structure inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-12, and proliferation of antigen-specific CD4(+) T-cells. This suggests that OmC2 may suppress the host's adaptive immune response. Immunization of mice with OmC2 significantly suppressed the survival of O. moubata in infestation experiments. We conclude that OmC2 is a promising target for the development of a novel anti-tick vaccine to control O. moubata populations and combat the spread of associated diseases.
C1 [Salat, Jiri; Kotsyfakis, Michalis; Grunclova, Lenka; Horka, Helena; Kopacek, Petr; Kopecky, Jan] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
[Salat, Jiri; Grunclova, Lenka; Horka, Helena; Kopacek, Petr; Kopecky, Jan] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
[Paesen, Guido C.; Majtan, Juraj; Nunn, Miles A.] Ctr Ecol & Hydrol, Oxford OX1 3SR, England.
[Rezacova, Pavlina; Kovarova, Zuzana; Sanda, Miloslav; Brynda, Jiri; Horn, Martin; Mares, Michael] Acad Sci Czech Republic, Inst Organ Chem & Biochem, CR-16610 Prague 6, Czech Republic.
[Rezacova, Pavlina; Brynda, Jiri] Acad Sci Czech Republic, Inst Mol Genet, Prague 16610 6, Czech Republic.
[Kotsyfakis, Michalis; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Kovarova, Zuzana] Charles Univ Prague, Fac Sci, Dept Biochem, Prague 12843 2, Czech Republic.
RP Salat, J (reprint author), Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Branisovska 31, CR-37005 Ceske Budejovice, Czech Republic.
EM george@paru.cas.cz; mares@uochb.cas.cz
RI Mares, Michael/B-2413-2009; Nunn, Miles/E-9233-2010; Maloy Rezacova,
Pavlina/G-3600-2014; Kopacek, Petr/G-8414-2014; Langhansova, Helena
/G-9292-2014; Kotsyfakis, Michail/G-9525-2014; Kopecky, Jan/G-9347-2014;
Brynda, Jiri/G-2760-2014; Horn, Martin/A-8701-2008;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Horn,
Martin/0000-0001-9110-2018; Majtan, Juraj/0000-0002-7268-1584
FU Grant Agency of the Academy of Sciences of the Czech Republic
[KJB500960702, IAA600960811]; Grant Agency of the Czech Republic
[P207/10/2183]; Research Center LC06009 [Z60220518, 740550506,
MSM-123100003]; UK Natural Environment Research Council
FX This work was supported by the Grant Agency of the Academy of Sciences
of the Czech Republic [grant numbers KJB500960702, IAA600960811], the
Grant Agency of the Czech Republic [grant number P207/10/2183], Research
Center LC06009 [research projects Z60220518, 740550506 and
MSM-123100003] and by the UK Natural Environment Research Council.
NR 40
TC 23
Z9 23
U1 2
U2 11
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 JUL 1
PY 2010
VL 429
BP 103
EP 112
DI 10.1042/BJ20100280
PN 1
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 619GY
UT WOS:000279418500011
PM 20545626
ER
PT J
AU Lu, JJ
Meng, LH
Shankavaram, UT
Zhua, CH
Tong, LJ
Chen, G
Lin, LP
Weinstein, JN
Ding, J
AF Lu, Jin-Jian
Meng, Ling-Hua
Shankavaram, Uma T.
Zhua, Cai-Hua
Tong, Lin-Jiang
Chen, Guang
Lin, Li-Ping
Weinstein, John N.
Ding, Jian
TI Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces
apoptosis in c-MYC-overexpressing tumor cells
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Dihydroartemisinin; NCI-60; c-MYC; Apoptosis; GSK 3 beta
ID IN-VITRO; ANTIMALARIAL ARTESUNATE; COLORECTAL-CARCINOMA; HISTONE
GAMMA-H2AX; PROTEIN STABILITY; CANCER-CELLS; GROWTH; ARTEMISININ;
EXPRESSION; ACTIVATION
AB Artemisinin and its derivatives (ARTS) are effective antimalarial drugs and also possess profound anticancer activity. However, the mechanism accounted for its distinctive activity in tumor cells remains unelucidated. We computed Pair wise Pearson correlation coefficients to identify genes that show significant correlation with ARTs activity in NCI-55 cell lines using data obtained from studies with HG-U133A Affymetrix chip. We found c-myc is one of the genes that showed the highest positive correlation coefficients among the probe sets analyzed (r = 0.585, P < 0.001). Dihydroartemisinin (DHA), the main active metabolite of ARTs, induced significant apoptosis in HL-60 and HCT116 cells that express high levels of c-MYC. Stable knockdown of c-myc abrogated DHA-induced apoptosis in HCT116 cells. Conversely, forced expression of c-myc in NIH3T3 cells sensitized these cells to DHA-induced apoptosis. Interestingly. DHA irreversibly down-regulated the protein level of c-MYC in DHA-sensitive HCT116 cells, which is consistent to persistent G1 phase arrest induced by DHA. Further studies demonstrated that DHA accelerated the degradation of c-MYC protein and this process was blocked by pretreatment with the proteasome inhibitor MG-132 or GSK 3 beta inhibitor LiCl in HCT116 cells. Taken together, ARTs might be useful in the treatment of c-MYC-overexpressing tumors. We also suggest that c-MYC may potentially be a biomarker candidate for prediction of the antitumor efficacies of ARTS. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lu, Jin-Jian; Meng, Ling-Hua; Zhua, Cai-Hua; Tong, Lin-Jiang; Chen, Guang; Lin, Li-Ping; Ding, Jian] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China.
[Shankavaram, Uma T.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
RP Meng, LH (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China.
EM lhmeng@mail.shcnc.ac.cn; jding@mail.shcnc.ac.cn
FU National Natural Science of China [30701026, 30721005]; National Science
& Technology Major Project "Key New Drug Creation and Manufacturing
Program" [2009ZX09301-001]
FX This work was supported by the National Natural Science of China (nos.
30701026 and 30721005), National Science & Technology Major Project "Key
New Drug Creation and Manufacturing Program" (2009ZX09301-001). We thank
Dr. Qin Chen and Dr. Zhi-Xiang Zhang for their help in the real-time PCR
assay. We also thank Dr. Yi Jiang for his help in establishing DHA
resistant HCT116/R cell line.
NR 48
TC 46
Z9 52
U1 1
U2 16
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 JUL 1
PY 2010
VL 80
IS 1
BP 22
EP 30
DI 10.1016/j.bcp.2010.02.016
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 593XW
UT WOS:000277497600003
PM 20206143
ER
PT J
AU Csordas, G
Varnai, P
Golenar, T
Roy, S
Purkins, G
Balla, T
Hajnoczky, G
AF Csordas, Gyoergy
Varnai, Peter
Golenar, Tuende
Roy, Swati
Purkins, George
Balla, Tamas
Hajnoczky, Gyoergy
TI Calcium signalling and ER-mitochondrial communication
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
CT 16th European Bioenergetics Conference
CY JUL 17-22, 2010
CL Old Lib Univ Warsaw, Warsaw, POLAND
SP Nencki Inst Expt Biol, Section of Bioenergetics of the Polish Biochemical Soc
HO Old Lib Univ Warsaw
C1 [Csordas, Gyoergy; Golenar, Tuende; Roy, Swati; Purkins, George; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Varnai, Peter] Semmelweis Univ Budapest, Dept Physiol, Budapest, Hungary.
[Balla, Tamas] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA.
EM gyorgy.hajnoczky@jefferson.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2010
VL 1797
SU S
BP 121
EP 121
DI 10.1016/j.bbabio.2010.04.361
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 622KR
UT WOS:000279662500336
ER
PT J
AU Youle, RJ
AF Youle, Richard J.
TI Role of the mitochondrial kinase Pink1 in Parkin recruitment and
mitophagy
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
CT 16th European Bioenergetics Conference
CY JUL 17-22, 2010
CL Old Lib Univ Warsaw, Warsaw, POLAND
SP Nencki Inst Expt Biol, Section of Bioenergetics of the Polish Biochemical Soc
HO Old Lib Univ Warsaw
C1 [Youle, Richard J.] NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2010
VL 1797
SU S
BP 141
EP 141
DI 10.1016/j.bbabio.2010.04.421
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 622KR
UT WOS:000279662500393
ER
PT J
AU Biancalana, M
Koide, S
AF Biancalana, Matthew
Koide, Shohei
TI Molecular mechanism of Thioflavin-T binding to amyloid fibrils
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Review
DE Cross-beta; Amyloid dye; Protein design; Molecular dynamics simulation;
Molecular recognition; Self-assembly
ID SELF-ASSEMBLY MIMICS; CONGO RED; ALZHEIMERS-DISEASE; DYNAMICS
SIMULATIONS; ATOMIC STRUCTURES; BETA; INSULIN; PROTEIN; SHEET;
AGGREGATION
AB Intense efforts to detect, diagnose, and analyze the kinetic and structural properties of amyloid fibrils have generated a powerful toolkit of amyloid-specific molecular probes. Since its first description in 1959, the fluorescent dye Thioflavin-T (ThT) has become among the most widely used "gold standards" for selectively staining and identifying amyloid fibrils both in vivo and in vitro. The large enhancement of its fluorescence emission upon binding to fibrils makes ThT a particularly powerful and convenient tool. Despite its widespread use in clinical and basic science applications, the molecular mechanism for the ability of ThT to recognize diverse types of amyloid fibrils and for the dye's characteristic fluorescence has only begun to be elucidated. Here, we review recent progress in the understanding of ThT-fibril interactions at an atomic resolution. These studies have yielded important insights into amyloid structures and the processes of fibril formation, and they also offer guidance for designing the next generation of amyloid assembly diagnostics, inhibitors, and therapeutics. (C) 2010 Elsevier BM. All rights reserved.
C1 [Koide, Shohei] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
[Biancalana, Matthew] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Biancalana, Matthew] MRC Ctr, Ctr Prot Engn, Cambridge CB2 0QH, England.
RP Koide, S (reprint author), Univ Chicago, Dept Biochem & Mol Biol, 929 E 57th St, Chicago, IL 60637 USA.
EM skoide@uchicago.edu
OI Biancalana, Matthew/0000-0002-1078-1838; Koide,
Shohei/0000-0001-5473-4358
FU NIH-Cambridge
FX M. Biancalana thanks the NIH-Cambridge Scholars Program for support.
NR 66
TC 355
Z9 358
U1 39
U2 238
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD JUL
PY 2010
VL 1804
IS 7
BP 1405
EP 1412
DI 10.1016/j.bbapap.2010.04.001
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 609OZ
UT WOS:000278667700001
PM 20399286
ER
PT J
AU de Castro, S
Maruoka, H
Hong, KL
Kilbey, SM
Costanzi, S
Hechler, B
Brown, GG
Gachet, C
Harden, TK
Jacobson, KA
AF de Castro, Sonia
Maruoka, Hiroshi
Hong, Kunlun
Kilbey, S. Michael, II
Costanzi, Stefano
Hechler, Beatrice
Brown, Garth G., Jr.
Gachet, Christian
Harden, T. Kendall
Jacobson, Kenneth A.
TI Functionalized Congeners of P2Y(1) Receptor Antagonists: 2-Alkynyl
(N)-Methanocarba 2 '-Deoxyadenosine 3 ',5 '-Bisphosphate Analogues and
Conjugation to a Polyamidoamine (PAMAM) Dendrimer Carrier
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; A(3) ADENOSINE RECEPTOR; BETA(2)-ADRENERGIC
RECEPTOR; NUCLEOTIDE RECEPTORS; PLATELET-AGGREGATION; CRYSTAL-STRUCTURE;
ENHANCED POTENCY; CLICK CHEMISTRY; DRUG DISCOVERY; MICE
AB The P2Y(1) receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3 ',5 '-bisphosphate antagonists of the P2Y(1) receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N-6-methyl-(N)-methanocarba-2 '-deoxyadenosine-3 ',5 '-bisphosphates containing extended 2-alkynyl chains was designed, and binding all at the human (h) P2Y(1) receptor detertmined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K-i 23 nM) and extended amine congener 15 (K-i 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended epsilon-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y(1) receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y(1) receptor modeling and ligand docking. Attempted P2Y(1) antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to produce a multivalent conjugate exhibiting a desired biological effect, i.e., antithrombotic action.
C1 [Jacobson, Kenneth A.] NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
[Costanzi, Stefano] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Brown, Garth G., Jr.] PerkinElmer Inc, Waltham, MA 02451 USA.
[Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
[Hong, Kunlun; Kilbey, S. Michael, II] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
[Hechler, Beatrice; Gachet, Christian] Univ Strasbourg, INSERM, UMR S949, EFS Alsace, Strasbourg, France.
RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009; Costanzi,
Stefano/G-8990-2013; Hong, Kunlun/E-9787-2015; Hechler,
Beatrice/D-4227-2017; Gachet, Christian/H-9156-2016;
OI de castro, sonia/0000-0002-3838-6856; Jacobson,
Kenneth/0000-0001-8104-1493; Hong, Kunlun/0000-0002-2852-5111; Costanzi,
Stefano/0000-0003-3183-7332
FU National Institute of General Medical Sciences [GM38213]; Scientific
User Facilities Division, Office of Basic Energy Sciences, U.S.
Department of Energy; Ministerio de Educacien y Ciencia (Spain); Asubio
Pharmaceuticals; NIH, National Institute of Diabetes and Digestive and
Kidney Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes and Digestive and Kidney Diseases,
and a grant (GM38213) from the National Institute of General Medical
Sciences. We thank Dr. John Lloyd and Dr. Noel Whittaker (NIDDK) for the
mass spectral determinations. Research conducted at the Center for
Nanophase Materials Sciences at Oak Ridge National Laboratory is
sponsored by the Scientific User Facilities Division, Office of Basic
Energy Sciences, U.S. Department of Energy. S. de Castro thanks
Ministerio de Educacien y Ciencia (Spain) for financial support. H.
Maruoka thanks Asubio Pharmaceuticals for financial support.
NR 47
TC 13
Z9 13
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD JUL
PY 2010
VL 21
IS 7
BP 1190
EP 1205
DI 10.1021/bc900569u
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 627GS
UT WOS:000280028100010
PM 20565071
ER
PT J
AU Tost, H
Lipska, BK
Vakkalanka, R
Lemaitre, H
Callicott, JH
Mattay, VS
Kleinman, JE
Marenco, S
Weinberger, DR
AF Tost, Heike
Lipska, Barbara K.
Vakkalanka, Radhakrishna
Lemaitre, Herve
Callicott, Joseph H.
Mattay, Venkata S.
Kleinman, Joel E.
Marenco, Stefano
Weinberger, Daniel R.
TI No Effect of a Common Allelic Variant in the Reelin Gene on Intermediate
Phenotype Measures of Brain Structure, Brain Function, and Gene
Expression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Gene expression; intermediate phenotype study; neuroimaging; neuronal
development; reelin; schizophrenia
ID SCHIZOPHRENIA; ASSOCIATION; MECHANISMS; DISEASE; DISC1; RISK
AB Background: A recent genome-wide association study linked a common variant in RELN (rs7341475G) with risk for schizophrenia in women. In the largest neuroimaging intermediate phenotype study reported so far, we evaluated the effect of rs7341475 on an extended array of different neuroscientific measures.
Methods: Brain structure was evaluated with voxel-based morphometry and diffusion tensor imaging. Brain function during working memory was examined with functional magnetic resonance imaging. The RELN expression was determined in postmortem brain tissue of the dorsolateral prefrontal cortex and hippocampus. A total of 736 datasets were examined (voxel-based morphometry: n = 230, diffusion tensor imaging: n = 93, functional magnetic resonance imaging: n = 308, RELN expression: n = 105).
Results: Our analyses did not provide evidence for a significant main effect of gene or gene x sex interaction effect on any of the examined measures.
Conclusions: This study does not suggest a significant impact of rs7341475 on brain structure, function, and RELN expression, arguing that this single nucleotide polymorphism and others linked with it do not affect brain measures related to the biology of schizophrenia.
C1 [Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Natl Inst Hlth,Dept Hlth & Human Serv,IRP, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Natl Inst Hlth,Dept Hlth & Human Serv,IRP, 10 Ctr Dr,Room 3C103, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
RI Marenco, Stefano/A-2409-2008; Callicott, Joseph/C-9102-2009;
OI Marenco, Stefano/0000-0002-2488-2365; Callicott,
Joseph/0000-0003-1298-3334; Lemaitre, Herve/0000-0002-5952-076X
FU National Institute of Mental Health, National Institutes of Health
(NIH); Deutsche Forschungsgemeinschaft-NIH
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(NIH), and a Deutsche Forschungsgemeinschaft-NIH scholarship grant to
HT.
NR 20
TC 11
Z9 12
U1 1
U2 2
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 JUL 1
PY 2010
VL 68
IS 1
BP 105
EP 107
DI 10.1016/j.biopsych.2010.02.023
PG 3
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 616KH
UT WOS:000279207800014
PM 20434133
ER
PT J
AU Pavletic, SZ
Kumar, S
Mohty, M
de Lima, M
Foran, JM
Pasquini, M
Zhang, MJ
Giralt, S
Bishop, MR
Weisdorf, D
AF Pavletic, Steven Z.
Kumar, Shaji
Mohty, Mohamad
de Lima, Marcos
Foran, James M.
Pasquini, Marcelo
Zhang, Mei-Jie
Giralt, Sergio
Bishop, Michael R.
Weisdorf, Daniel
TI NCI First International Workshop on the Biology, Prevention, and
Treatment of Relapse after Allogeneic Hematopoietic Stem Cell
Transplantation: Report from the Committee on the Epidemiology and
Natural History of Relapse following Allogeneic Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic hematorpoietic stem cell transplantation; Relapse
ID VERSUS-HOST-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA;
BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; CHRONIC
LYMPHOCYTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; NON-HODGKIN-LYMPHOMA;
HLA-IDENTICAL SIBLINGS; UMBILICAL-CORD BLOOD; CHRONIC MYELOGENOUS
LEUKEMIA
AB Allogeneic hematopoietic stem cell transplantation (alloHSCT) is increasingly being used for treatment of hematologic malignancies, and the immunologic graft-versus-tumor effect (GVT) provides its therapeutic effectiveness. Disease relapse remains a cause of treatment failure in a significant proportion of patients undergoing alloHSCT without improvements over the last 2-3 decades. We summarize here current data and outline future research regarding the epidemiology, risk factors, and outcomes of relapse after alloHSCT. Although some factors (eg, disease status at alloHSCT or graft-versus-host disease [GVHD] effects) are common, other disease-specific factors may be unique. The impact of reduced-intensity regimens on relapse and survival still need to be assessed using contemporary supportive care and comparable patient populations. The outcome of patients relapsing after an alloHSCT generally remains poor even though interventions including donor leukocyte infusions can benefit some patients. Trials examining targeted therapies along with improved safety of alloHSCT may result in improved outcomes, yet selection bias necessitates prospective assessment to gauge the real contribution of any new therapies. Ongoing chronic GVHD (cGVHD) or other residual post-alloHSCT morbidities may limit the applicability of new therapies. Developing strategies to promptly identify patients as alloHSCT candidates, while malignancy is in a more treatable stage, could decrease relapses rates after alloHSCT. Better understanding and monitoring of minimal residual disease posttransplant could lead to novel preemptive treatments of relapse. Analyses of larger cohorts through multicenter collaborations or registries remain essential to probe questions not amenable to single center or prospective studies. Studies need to provide data with detail on disease status, prior treatments, biologic markers, and posttransplant events. Stringent statistical methods to study relapse remain an important area of research. The opportunities for improvement in prevention and management of post-alloHSCT relapse are apparent, but clinical discipline in their careful study remains important. Biol Blood Marrow Transplant 16: 871-890 (2010) (C) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights received.
C1 [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN 55455 USA.
[Pavletic, Steven Z.; Bishop, Michael R.] NCI, Bethesda, MD 20892 USA.
[Kumar, Shaji] Mayo Clin, Rochester, MN USA.
[Mohty, Mohamad] CHU Nantes, F-44035 Nantes, France.
[Mohty, Mohamad] Univ Nantes, INSERM, U892, Nantes, France.
[de Lima, Marcos; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Foran, James M.] Univ Alabama, Birmingham, AL USA.
[Pasquini, Marcelo; Zhang, Mei-Jie] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
RP Weisdorf, D (reprint author), Univ Minnesota, MMC 480, Minneapolis, MN 55455 USA.
EM weisd001@umn.edu
RI Kumar, Shaji/A-9853-2008
OI Kumar, Shaji/0000-0001-5392-9284
FU National Cancer Institute
FX This work was supported by the National Cancer Institute.
NR 244
TC 49
Z9 49
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2010
VL 16
IS 7
BP 871
EP 890
DI 10.1016/j.bbmt.2010.04.004
PG 20
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 618PG
UT WOS:000279367500001
PM 20399876
ER
PT J
AU Fall-Dickson, JM
Mitchell, SA
Marden, S
Ramsay, ES
Guadagnini, JP
Wu, TX
John, LS
Pavletic, SZ
AF Fall-Dickson, Jane M.
Mitchell, Sandra A.
Marden, Susan
Ramsay, Edward S.
Guadagnini, Jean-Pierre
Wu, Tianxia
John, Lena St.
Pavletic, Steven Z.
CA Natl Inst Hlth
TI Oral Symptom Intensity, Health-Related Quality of Life, and Correlative
Salivary Cytokines in Adult Survivors of Hematopoietic Stem Cell
Transplantation with Oral Chronic Graft-versus-Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Oral chronic graft-versus-host disease; Quality of life; Symptoms
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; RADIATION-INDUCED
XEROSTOMIA; CLINICAL-TRIALS; NECK-CANCER; T-CELLS; MODULATED
RADIOTHERAPY; FUNCTIONAL ASSESSMENT; B-CELLS; FACT-G
AB Oral chronic graft-versus-host disease (cGVHD) is a frequent, clinically significant sequela of allogeneic hematopoietic stem cell transplantation (HSCT). This study was designed to elucidate relationships among clinical characteristics of oral cGVHD and related oral pain and oral dryness, salivary proinflammatory cytokine interleukin (IL)-6 and IL-1 alpha concentrations, and health-related quality of life (HRQL). An understanding of the characteristics and correlates of oral cGVHD manifestations and related symptoms, such as oral dryness, is fundamental to the development of therapeutic interventions. Oral cGVHD severity was assessed with the Oral Mucositis Rating Scale (OMRS). Oral pain and perceived intensity of oral dryness were self-reported via a visual analog scale and a numeric rating scale, respectively. HRQL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G). Salivary IL-1 alpha and IL-6 concentrations were measured by enzyme-linked immunosorbent assay. All 42 adult subjects (59% males) had clinician-assessed oral cGVHD by the OMRS scale (mean score, 18.38 +/- 12.99; range, 2-46). Oral dryness (in 43% of subjects; mean OMRS score, 2.56 +/- 3.45; range, 0-10) was more prevalent than oral pain (8%; mean score, 0.13 +/- 0.47). Salivary IL-6 was associated with oral cGVHD severity (r = 0.49; P < .01), oral ulceration (r = 0.38; P = .04), and erythema (r = 0.63; P < .01). FACT-G total score and physical and emotional well-being subscale scores were meaningfully lower than U.S. population normative values. Participants with more severe oral cGVHD manifestations had significantly inferior social/family well being (r = -0.49; P < .01). Oral dryness was associated with higher salivary IL-1 alpha (r = 0.41; P = .04) and, controlling for cGVHD severity, with lower HRQL (r = -0.41; P = .03). Subjects with moderate to severe oral dryness tended to report the poorest overall HRQL. This study provides preliminary evidence of the relationship between oral dryness and HRQL, the contribution of oral cGVHD to inferior HRQL, and the association between IL-6 and oral cGVHD severity, ulceration, and erythema. The high prevalence of oral dryness and its relationship to HRQL in a sample of subjects with oral cGVHD underscores the importance of improving our evaluation and management of this symptom in long-term survivors of allogeneic HSCT. The positive associations between IL-6 and oral cGVHD severity and erythema, as well as the positive trend with oral ulceration, warrant further exploration of this cytokine as a potential biomarker of active oral cGVHD. Bid Blood Marrow Transplant 16: 948-956 (2010) (C) Published by Elsevier Inc.
C1 [Fall-Dickson, Jane M.; John, Lena St.] NINR, Mucosal Injury Unit, Symptom Management Branch, NIH, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Marden, Susan] NINR, Off Extramural Programs, NIH, Bethesda, MD 20892 USA.
[Guadagnini, Jean-Pierre] Natl Inst Dent & Craniofacial Res, Dent Serv, NIH, Bethesda, MD USA.
[Wu, Tianxia] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Fall-Dickson, JM (reprint author), NINR, Mucosal Injury Unit, Symptom Management Branch, NIH, 10 Clin Res Ctr,Room 2NE 1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dicksonj@mail.nih.gov
FU NCI
FX The authors thank Dr. Mary E. Kerr, National Institute of Nursing
Research, and Dr. Joan K. Austin, Indiana University School of Nursing,
for useful discussions regarding manuscript development. They also thank
Dr. Matin Imanguli, DDS, formerly of the Experimental Transplantation
and immunology Branch, National Cancer Institute (NCI) for saliva sample
acquisition; Sherri Gollins, BS and Sharon Mitchell, National Institute
of Dental and Craniofacial Research (NIDCR), for assistance with the
saliva collection; and Dr Gabor Illei, NIDCR, for
submandibular/sublingual saliva sample acquisition from healthy
volunteers. We also acknowledge with gratitude the subjects in the
NCI-sponsored Chronic Graft-versus-Host Disease Natural History Protocol
(clinicaltrials.gov #NCT00331968).
NR 56
TC 15
Z9 18
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2010
VL 16
IS 7
BP 948
EP 956
DI 10.1016/j.bbmt.2010.01.017
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 618PG
UT WOS:000279367500007
PM 20139026
ER
PT J
AU Chatterjee, K
Lin-Gibson, S
Wallace, WE
Parekh, SH
Lee, YJ
Cicerone, MT
Young, MF
Simon, CG
AF Chatterjee, Kaushik
Lin-Gibson, Sheng
Wallace, William E.
Parekh, Sapun H.
Lee, Young Jong
Cicerone, Marcus T.
Young, Marian F.
Simon, Carl G., Jr.
TI The effect of 3D hydrogel scaffold modulus on osteoblast differentiation
and mineralization revealed by combinatorial screening
SO BIOMATERIALS
LA English
DT Article
DE Tissue engineering; Hydrogels; Osteoblast; Combinatorial methods; Matrix
stiffness; Graded tissues
ID CELL-INTERACTIONS; MC3T3-E1 CELLS; STEM-CELLS; GRADIENTS; BIOMATERIALS;
EXPRESSION; SPECTROSCOPY; INTERFACE; LIBRARIES; SURFACES
AB Cells are known to sense and respond to the physical properties of their environment and those of tissue scaffolds. Optimizing these cell material interactions is critical in tissue engineering. In this work, a simple and inexpensive combinatorial platform was developed to rapidly screen three-dimensional (3D) tissue scaffolds and was applied to screen the effect of scaffold properties for tissue engineering of bone. Differentiation of osteoblasts was examined in poly(ethylene glycol) hydrogel gradients spanning a 30-fold range in compressive modulus (approximate to 10 kPa to approximate to 300 kPa). Results demonstrate that material properties (gel stiffness) of scaffolds can be leveraged to induce cell differentiation in 3D culture as an alternative to biochemical cues such as soluble supplements, immobilized biomolecules and vectors, which are often expensive, labile and potentially carcinogenic. Gel moduli of approximate to 225 kPa and higher enhanced osteogenesis. Furthermore, it is proposed that material-induced cell differentiation can be modulated to engineer seamless tissue interfaces between mineralized bone tissue and softer tissues such as ligaments and tendons. This work presents a combinatorial method to screen biological response to 3D hydrogel scaffolds that more closely mimics the 3D environment experienced by cells in vivo. Published by Elsevier Ltd.
C1 [Chatterjee, Kaushik; Lin-Gibson, Sheng; Wallace, William E.; Parekh, Sapun H.; Lee, Young Jong; Cicerone, Marcus T.; Simon, Carl G., Jr.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA.
[Chatterjee, Kaushik; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Simon, CG (reprint author), Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA.
EM carl.simon@nist.gov
RI Lee, Young Jong/B-7129-2008
OI Lee, Young Jong/0000-0001-7754-3001
FU National Research Council of the National Academy of Sciences; NIST,
NIH/NIBIB [R21 EB006497-01]; Intramural Program of the NIH/NIDCR
(National Institute of Dental and Craniofacial Research)
FX Authors gratefully acknowledge technical assistance from Kathy Flynn
(NIST) and Ed Parry (ADA-NIST) and insightful discussions with Kathryn
L. Beers (NIST). This research was performed while K.C. and S.H.P. held
Research Associateship Awards from the National Research Council of the
National Academy of Sciences in the Joint NIH-NIBIB/NIST and the NIST
Postdoctoral Programs, respectively (National Institutes of
Health-National Institute of Biomedical Imaging and
Bioengineering/National Institute of Standards and Technology). This
work was supported by NIST, NIH/NIBIB R21 EB006497-01 and the Intramural
Program of the NIH/NIDCR (National Institute of Dental and Craniofacial
Research). The "standard deviation" (S.D.) is the same as the "combined
standard uncertainty of the mean" for the purposes of this work. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of NIH, NIBIB, NIDCR or NIST.
This article, a contribution of NIST, is not subject to US copyright.
Certain equipment and instruments or materials are identified in the
paper to adequately specify the experimental details. Such
identification does not imply recommendation by NIST, nor does it imply
the materials are necessarily the best available for the purpose.
NR 45
TC 112
Z9 114
U1 5
U2 70
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD JUL
PY 2010
VL 31
IS 19
BP 5051
EP 5062
DI 10.1016/j.biomaterials.2010.03.024
PG 12
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 606YW
UT WOS:000278466100002
PM 20378163
ER
PT J
AU Yu, QS
Holloway, HW
Luo, WM
Lahiri, DK
Brossi, A
Greig, NH
AF Yu, Qian-sheng
Holloway, Harold W.
Luo, Weiming
Lahiri, Debomoy K.
Brossi, Arnold
Greig, Nigel H.
TI Long-acting anticholinesterases for myasthenia gravis: synthesis and
activities of quaternary phenylcarbamates of neostigmine, pyridostigmine
and physostigmine
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Myasthenia gravis; Pyridostigmine; Neostigmine; N-Phenylcarbamate
analogues of; (-)-physostigmine; (-)-Phenserine; (-)-Cymserine;
Congenital myasthenic syndromes
ID CHOLINESTERASE-INHIBITORS; ALZHEIMERS-DISEASE; CLINICAL
PHARMACOKINETICS; SELECTIVE INHIBITORS; BUTYRYLCHOLINESTERASE;
ACETYLCHOLINESTERASE; PHENSERINE; KINETICS; ANALOGS; RECOGNITION
AB The N-monophenylcarbamate analogues of neostigmine methyl sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-methylammonium analogues of (-)-phenserine (12), (-)-tolserine (14), (-)-cymserine (16) and (-)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5-8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis. Published by Elsevier Ltd.
C1 [Yu, Qian-sheng; Holloway, Harold W.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Biomed Res Ctr,NIH, Baltimore, MD 21224 USA.
[Luo, Weiming] MedStar Res Inst, Hyattsville, MD 20782 USA.
[Lahiri, Debomoy K.] Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA.
[Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Biomed Res Ctr,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Greign@grc.nia.nih.gov
FU National Institute on Aging; National Institutes of Health; National
Institutes of health [AG18379, AG18884]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health, and by
National Institutes of health grants (AG18379 and AG18884) to D. K. L.
The authors are grateful for the aid and input of Scott MacDonald,
Advanced Chemistry Development, Inc., Toronto, ON, Canada, for
determination of Log D values of charged compounds. Animal studies were
undertaken on an approved protocol in accord with the Animal Care and
Use Committees of the Intramural Research Program, National Institute on
Aging, and followed National Institutes of Health guidelines. The
authors declare no conflicts of interest relating to the described
research.
NR 42
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Z9 20
U1 2
U2 24
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 JUL 1
PY 2010
VL 18
IS 13
BP 4687
EP 4693
DI 10.1016/j.bmc.2010.05.022
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 613VN
UT WOS:000279011000010
PM 20627738
ER
PT J
AU Bokesch, HR
Cartner, LK
Fuller, RW
Wilson, JA
Henrich, CJ
Kelley, JA
Gustafson, KR
McMahon, JB
McKee, TC
AF Bokesch, Heidi R.
Cartner, Laura K.
Fuller, Richard W.
Wilson, Jennifer A.
Henrich, Curtis J.
Kelley, James A.
Gustafson, Kirk R.
McMahon, James B.
McKee, Tawnya C.
TI Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine
crinoids
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Marine natural products; Napthopyrones; Crinoids; ABCG2
ID CANCER RESISTANCE PROTEIN; ABCG2
AB Five new naphthopyrones (1-5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4H-naphtho[2,3-b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether (6-11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with <60% inhibition of ABCG2-mediated transport as compared to the positive control fumitremorgin C. None of the linear naphthopyrones inhibited ABCG2-mediated efflux. Published by Elsevier Ltd.
C1 [Bokesch, Heidi R.; Cartner, Laura K.; Fuller, Richard W.; Wilson, Jennifer A.; Henrich, Curtis J.; Gustafson, Kirk R.; McMahon, James B.; McKee, Tawnya C.] NCI, Mol Targets Lab, Frederick, MD 21702 USA.
[Bokesch, Heidi R.; Cartner, Laura K.; Henrich, Curtis J.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Kelley, James A.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
RP McKee, TC (reprint author), NCI, Mol Targets Lab, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E and has been supported in part by the
Intramural Research Program of NIH, National Cancer Institute, Center
for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. We
thank D. Newman (NPB) for the contract collection, and T. McCloud for
extractions.
NR 13
TC 5
Z9 6
U1 1
U2 7
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 JUL 1
PY 2010
VL 20
IS 13
BP 3848
EP 3850
DI 10.1016/j.bmcl.2010.05.057
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 609GT
UT WOS:000278644700002
PM 20627559
ER
PT J
AU Topol, I
Collins, J
Nemukhin, A
AF Topol, Igor
Collins, Jack
Nemukhin, Alexander
TI Modeling spectral tuning in monomeric teal fluorescent protein mTFP1
SO BIOPHYSICAL CHEMISTRY
LA English
DT Article
DE Teal fluorescent protein mTFP1; Photoabsorption spectra; Quantum
calculations; Mutation influence
ID GREEN; CHROMOPHORE; BEHAVIOR; COLOR; GFP
AB We present results of theoretical studies of the variants of the monomeric teal fluorescent protein from Clavularia coral (mTFP1) which present promising members from the GFP family. Predictions of quantum chemical approaches including density functional theory and semiempirical approximations are presented for the model systems which mimic the chromophores in different environments We describe the excitation energy spectrum of the cyan mTFP1 fluorescent protein with the original chromophore and with chromophore mutants Tyr67His and Tyr67Trp (C) 2010 Elsevier B.V All rights reserved
C1 [Topol, Igor; Collins, Jack] SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Ft Detrick, MD 21702 USA.
[Nemukhin, Alexander] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
[Nemukhin, Alexander] Russian Acad Sci, NM Emanuel Inst Biochem Phys, Moscow 119334, Russia.
RP Topol, I (reprint author), SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Ft Detrick, MD 21702 USA.
RI Nemukhin, Alexander/P-9662-2015
FU Advanced Biomedical Computing Center; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; Russian Foundation
for Basic Research [10-03-00085]; U.S. Government
FX We thank the staff and administration of the Advanced Biomedical
Computing Center for their support of this project. We thank Dr. Brian
Luke for very helpful comments This project has been funded in whole or
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract number HHSN261200800001E The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organization imply
endorsement by the U.S. Government. This work is partly supported by the
Russian Foundation for Basic Research (project # 10-03-00085).
NR 13
TC 13
Z9 13
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-4622
J9 BIOPHYS CHEM
JI Biophys. Chem.
PD JUL
PY 2010
VL 149
IS 3
BP 78
EP 82
DI 10.1016/j.bpc.2010.04.002
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA 609NH
UT WOS:000278663000002
PM 20442006
ER
PT J
AU Baker, SG
Darke, AK
Pinsky, P
Parnes, HL
Kramer, BS
AF Baker, Stuart G.
Darke, Amy K.
Pinsky, Paul
Parnes, Howard L.
Kramer, Barnett S.
TI Transparency and reproducibility in data analysis: the Prostate Cancer
Prevention Trial
SO BIOSTATISTICS
LA English
DT Article
DE Categorical data; Maximum likelihood; Missing data; Multinomial-Poisson
transformation; Propensity-to-be-missing score; Randomized trials
ID FINASTERIDE
AB With the analysis of complex, messy data sets, the statistics community has recently focused attention on "reproducible research," namely research that can be readily replicated by others. One standard that has been proposed is the availability of data sets and computer code. However, in some situations, raw data cannot be disseminated for reasons of confidentiality or because the data are so messy as to make dissemination impractical. For one such situation, we propose 2 steps for reproducible research: (i) presentation of a table of data and (ii) presentation of a formula to estimate key quantities from the table of data. We illustrate this strategy in the analysis of data from the Prostate Cancer Prevention Trial, which investigated the effect of the drug finasteride versus placebo on the period prevalence of prostate cancer. With such an important result at stake, a transparent analysis was important.
C1 [Baker, Stuart G.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Darke, Amy K.] Fred Hutchinson Canc Res Ctr, Ctr Stat, Seattle, WA 98109 USA.
[Pinsky, Paul] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, Execut Plaza N 3131,6130 Execut Blvd,Mail Stop Co, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU National Cancer Institute, Division of Cancer Prevention
[5U10CA037429-25]; Southwest Oncology Group CCOP Research Base,
PCPT/PCPT LTFU, and SELECT Programs; National Institutes of Health
FX National Cancer Institute, Division of Cancer Prevention
(5U10CA037429-25); Southwest Oncology Group CCOP Research Base,
PCPT/PCPT LTFU, and SELECT Programs; Division of Cancer Prevention in
the National Cancer Institute and the National Institutes of Health.
NR 7
TC 2
Z9 2
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2010
VL 11
IS 3
BP 413
EP 418
DI 10.1093/biostatistics/kxq004
PG 6
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 609WQ
UT WOS:000278689300012
PM 20173101
ER
PT J
AU Zhang, H
Olschwang, S
Yu, K
AF Zhang, Hong
Olschwang, Sylviane
Yu, Kai
TI Statistical inference on the penetrances of rare genetic mutations based
on a case-family design
SO BIOSTATISTICS
LA English
DT Article
DE Case-family design; Penetrance; Proportional hazards model; Rare
mutation; Unobserved risk factors
ID KIN-COHORT
AB We propose a formal statistical inference framework for the evaluation of the penetrance of a rare genetic mutation using family data generated under a kin-cohort type of design, where phenotype and genotype information from first-degree relatives (sibs and/or offspring) of case probands carrying the targeted mutation are collected. Our approach is built upon a likelihood model with some minor assumptions, and it can be used for age-dependent penetrance estimation that permits adjustment for covariates. Furthermore, the derived likelihood allows unobserved risk factors that are correlated within family members. The validity of the approach is confirmed by simulation studies. We apply the proposed approach to estimating the age-dependent cancer risk among carriers of the MSH2 or MLH1 mutation.
C1 [Zhang, Hong; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Zhang, Hong] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China.
[Olschwang, Sylviane] INSERM, U891, F-13009 Marseille, France.
[Olschwang, Sylviane] Inst J Paoli I Calmettes, Dept Oncogenet, F-13009 Marseille, France.
RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM yuka@mail.nih.gov
RI Olschwang, Sylviane/G-2716-2013
FU National Institutes of Health; Natural Science Foundation of China
[10701067]; Institut National du Cancer
FX Intramural Program of the National Institutes of Health to H.Z. and
K.Y.; Natural Science Foundation of China (10701067) to H.Z.; Institut
National du Cancer to S.O.
NR 14
TC 3
Z9 3
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2010
VL 11
IS 3
BP 519
EP 532
DI 10.1093/biostatistics/kxq009
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 609WQ
UT WOS:000278689300020
PM 20179148
ER
PT J
AU Kim, S
Sundaram, R
Louis, GMB
AF Kim, Sungduk
Sundaram, Rajeshwari
Louis, Germaine M. Buck
TI Joint modeling of intercourse behavior and human fecundability using
structural equation models
SO BIOSTATISTICS
LA English
DT Article
DE Conception; Fecundity; Intercourse; Latent variables; Markov chain Monte
Carlo; Menstrual cycle; Posterior distribution; Structural equation
model
ID BAYESIAN-ANALYSIS; HUMAN-FERTILITY; CONCEPTION; PREGNANCY; TIME;
FREQUENCY; OVULATION; WINDOW
AB Human fecundability is defined as the probability of conception during a menstrual cycle among couples at risk for pregnancy. It is highly relevant for understanding human reproduction and represents a series of highly interrelated and timed processes. The statistical literature has recognized the need to incorporate both biological and behavioral factors (Barrett and Marshall, 1969; Dunson and Stanford, 2005) when modeling conception probabilities, given that intercourse during the fertile window is a necessary but not sufficient criterion for conception. The heterogeneity of behaviors such as the timing and frequency of intercourse in a menstrual cycle needs to be considered when estimating conception. Here we propose a joint model of intercourse behavior and human fecundability through a classic conception probability model and a structural equation model (SEM) to accommodate intercourse during the menstrual cycle. The SEM part of the proposed model allows the dependency between intercourse behaviors on consecutive days in a menstrual cycle to vary across days. Consequently, the proposed model can accommodate not only a broad variety of intercourse patterns and dependency structures but also general covariate effects. Finally, we present a detailed analysis of the New York State Angler Cohort Prospective Pregnancy Study to illustrate the proposed methodology.
C1 [Kim, Sungduk; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
RP Sundaram, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM sundaramr2@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490; Sundaram,
Rajeshwari/0000-0002-6918-5002
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX Intramural research program of National Institutes of Health; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 26
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Z9 3
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2010
VL 11
IS 3
BP 559
EP 571
DI 10.1093/biostatistics/kxq006
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 609WQ
UT WOS:000278689300024
PM 20173100
ER
PT J
AU Loeb, S
Carter, HB
Schaeffer, EM
Ling, SM
Kettermann, A
Ferrucci, L
Metter, EJ
AF Loeb, Stacy
Carter, H. Ballentine
Schaeffer, Edward M.
Ling, Shari M.
Kettermann, Anna
Ferrucci, Luigi
Metter, E. Jeffrey
TI Bone mineral content and prostate cancer risk: data from the Baltimore
Longitudinal Study of Aging
SO BJU INTERNATIONAL
LA English
DT Article
DE bone density; prostate cancer; metastases; risk; calcium
ID CALCIUM INTAKE; DENSITY; MEN; PROGRESSION; INCIDENT; HORMONE; HEALTH;
MASS
AB OBJECTIVE
To determine whether there might be differences in bone mineral content (BMC) between men who develop life-threatening prostate cancer and those who do not, as bone is a common site of prostate cancer metastases.
SUBJECTS AND METHODS
From 1973 to 1984, BMC was serially measured in 519 participants (778 observations) as part of a longitudinal study of ageing. We examined the association between serial BMC measurements with the development of overall and high-risk prostate cancer over the next one to three decades. For all prostate cancer cases, BMC was censored at the time of diagnosis.
RESULTS
During a median (range) overall follow-up of 21.1 (0.2-35.0) years after the last BMC measurement, 76 (14.6%) men were later diagnosed with prostate cancer (18 high-risk and 58 not high-risk). BMC declined with age to a greater extent in healthy controls than among men diagnosed with prostate cancer (P = 0.018, likelihood ratio test), and tended to decline less in high-risk than non-high-risk cases.
CONCLUSION
The distribution of BMC was significantly different between men who did and did not develop prostate cancer, over an extended follow-up. Specifically, BMC appeared to decline to a greater extent with age among healthy controls than in men with prostate cancer, especially high-risk disease. The biology underlying the lesser decline in BMC among men with prostate cancer remains unclear, but suggests that host factors in the bony milieu might be associated with prostate cancer development and progression.
C1 [Loeb, Stacy; Carter, H. Ballentine; Schaeffer, Edward M.; Kettermann, Anna] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Ling, Shari M.; Ferrucci, Luigi; Metter, E. Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
RP Loeb, S (reprint author), 600 N Wolfe St,Marburg 1, Baltimore, MD 21287 USA.
EM stacyloeb@gmail.com
OI Loeb, Stacy/0000-0003-3933-9207
FU National Institute of Health, National Institute on Ageing
FX This research was supported by the Intramural Research Program of the
National Institute of Health, National Institute on Ageing.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUL
PY 2010
VL 106
IS 1
BP 28
EP 31
DI 10.1111/j.1464-410X.2009.09109.x
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 607PA
UT WOS:000278516600005
PM 20067459
ER
PT J
AU Chanock, SJ
AF Chanock, Stephen J.
TI The DARC side of GWAS
SO BLOOD
LA English
DT Editorial Material
ID GENOMEWIDE ASSOCIATION
C1 Natl Canc Inst, Bethesda, MD 20892 USA.
RP Chanock, SJ (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA.
NR 7
TC 1
Z9 1
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 JUL 1
PY 2010
VL 115
IS 26
BP 5285
EP 5286
PG 3
WC Hematology
SC Hematology
GA 619MV
UT WOS:000279435200003
PM 20595521
ER
PT J
AU Schnabel, RB
Baumert, J
Barbalic, M
Dupuis, J
Ellinor, PT
Durda, P
Dehghan, A
Bis, JC
Illig, T
Morrison, AC
Jenny, NS
Keaney, JF
Gieger, C
Tilley, C
Yamamoto, JF
Khuseyinova, N
Heiss, G
Doyle, M
Blankenberg, S
Herder, C
Walston, JD
Zhu, YY
Vasan, RS
Klopp, N
Boerwinkle, E
Larson, MG
Psaty, BM
Peters, A
Ballantyne, CM
Witteman, JCM
Hoogeveen, RC
Benjamin, EJ
Koenig, W
Tracy, RP
AF Schnabel, Renate B.
Baumert, Jens
Barbalic, Maja
Dupuis, Josee
Ellinor, Patrick T.
Durda, Peter
Dehghan, Abbas
Bis, Joshua C.
Illig, Thomas
Morrison, Alanna C.
Jenny, Nancy S.
Keaney, John F., Jr.
Gieger, Christian
Tilley, Cathy
Yamamoto, Jennifer F.
Khuseyinova, Natalie
Heiss, Gerardo
Doyle, Margaret
Blankenberg, Stefan
Herder, Christian
Walston, Jeremy D.
Zhu, Yanyan
Vasan, Ramachandran S.
Klopp, Norman
Boerwinkle, Eric
Larson, Martin G.
Psaty, Bruce M.
Peters, Annette
Ballantyne, Christie M.
Witteman, Jacqueline C. M.
Hoogeveen, Ron C.
Benjamin, Emelia J.
Koenig, Wolfgang
Tracy, Russell P.
TI Duffy antigen receptor for chemokines (Darc) polymorphism regulates
circulating concentrations of monocyte chemoattractant protein-1 and
other inflammatory mediators
SO BLOOD
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BLOOD-GROUP; DISEASE; ANTIGEN/RECEPTOR; CELLS;
GENE; ATHEROSCLEROSIS; CCR2; IDENTIFICATION; RECRUITMENT
AB To identify the genetic basis of circulating concentrations of monocyte chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses for MCP-1 in 3 independent cohorts (n = 9598). The strongest association was for serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the gene for Duffy antigen receptor for chemokines, a known vascular reservoir of proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10(-323)). This association was supported by family-based genetic linkage at a locus encompassing the DARC gene (genome-wide P = 8.0 * 10(-13)). Asp42Gly accounted for approximately 20% of the variability in serum MCP-1 concentrations and also was associated with serum concentrations of interleukin-8 and RANTES. While exploring a lack of association between this polymorphism and EDTA plasma MCP-1 concentrations (P = .82), we determined that both clotting and exogenous heparan sulfate (unfractionated heparin) released substantial amounts of MCP-1 from Darc. Quantitative immuno-flow cytometry failed to identify meaningful Asp42Gly-associated differences in Darc expression, suggesting that a functional change is responsible for the differential cytokine binding. We conclude that Asp42Gly is a major regulator of erythrocyte Darc-mediated cytokine binding and thereby the circulating concentrations of several proinflammatory cytokines. We have also identified for the first time 2 mechanisms for the release of reservoir chemokines with possible clinical implications. (Blood. 2010; 115(26):5289-5299)
C1 [Benjamin, Emelia J.] Boston Univ, Sch Med, Framingham Heart Study,Dept Med, Whitaker Cardiovasc Inst,Sect Prevent Med, Framingham, MA 01702 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Med,Sect Cardiol, Framingham, MA 01702 USA.
[Schnabel, Renate B.; Dupuis, Josee; Keaney, John F., Jr.; Yamamoto, Jennifer F.; Vasan, Ramachandran S.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Boston, MA USA.
[Schnabel, Renate B.; Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Gutenberg Heart Study, Mainz, Germany.
[Baumert, Jens; Illig, Thomas; Gieger, Christian; Klopp, Norman; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Barbalic, Maja; Morrison, Alanna C.; Heiss, Gerardo; Boerwinkle, Eric; Ballantyne, Christie M.; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Barbalic, Maja; Morrison, Alanna C.; Heiss, Gerardo; Boerwinkle, Eric; Ballantyne, Christie M.; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Dupuis, Josee; Yamamoto, Jennifer F.; Zhu, Yanyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham, MA 01702 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Durda, Peter; Jenny, Nancy S.; Tilley, Cathy; Doyle, Margaret; Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Dehghan, Abbas; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Khuseyinova, Natalie; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89081 Ulm, Germany.
[Herder, Christian] Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.
[Walston, Jeremy D.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Walston, Jeremy D.] Johns Hopkins Univ, Johns Hopkins Geriatr Ctr, Baltimore, MD USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Grp Hlth, Seattle, WA 98101 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Framingham, MA 01702 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study,Dept Med, Whitaker Cardiovasc Inst,Sect Prevent Med, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM ronh@bcm.tmc.edu; emelia@bu.edu; wolfgang.koenig@uniklinik-ulm.de;
russell.tracy@uvm.edu
RI Peters, Annette/A-6117-2011; Schnabel, Renate/F-6527-2014;
OI Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336;
Gieger, Christian/0000-0001-6986-9554; Dehghan,
Abbas/0000-0001-6403-016X; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970
FU NCRR NIH HHS [1S10RR163736-01A1, UL1RR025005]; NHGRI NIH HHS
[U01HG004402]; NHLBI NIH HHS [2K24HL04334, HL064753, HL076784, HL093328,
K24 HL105780, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022, R01 HL077449, R01 HL104156,
R01HL086694, R01HL087641, R01HL59367]; NIA NIH HHS [AG028321]; NIDA NIH
HHS [R21 DA027021]; NIDDK NIH HHS [DK080739]; NINDS NIH HHS [6R01-NS
17950]
NR 46
TC 55
Z9 55
U1 0
U2 9
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 JUL 1
PY 2010
VL 115
IS 26
BP 5289
EP 5299
DI 10.1182/blood-2009-05-221382
PG 11
WC Hematology
SC Hematology
GA 619MV
UT WOS:000279435200005
PM 20040767
ER
PT J
AU Harvey, RC
Mullighan, CG
Chen, IM
Wharton, W
Mikhail, FM
Carroll, AJ
Kang, HN
Liu, W
Dobbin, KK
Smith, MA
Carroll, WL
Devidas, M
Bowman, WP
Camitta, BM
Reaman, GH
Hunger, SP
Downing, JR
Willman, CL
AF Harvey, Richard C.
Mullighan, Charles G.
Chen, I-Ming
Wharton, Walker
Mikhail, Fady M.
Carroll, Andrew J.
Kang, Huining
Liu, Wei
Dobbin, Kevin K.
Smith, Malcolm A.
Carroll, William L.
Devidas, Meenakshi
Bowman, W. Paul
Camitta, Bruce M.
Reaman, Gregory H.
Hunger, Stephen P.
Downing, James R.
Willman, Cheryl L.
TI Rearrangement of CRLF2 is associated with mutation of JAK kinases,
alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in
pediatric B-progenitor acute lymphoblastic leukemia
SO BLOOD
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; MINIMAL RESIDUAL DISEASE; IN-VITRO;
MYELOPROLIFERATIVE DISORDERS; CLINICAL-SIGNIFICANCE; RISK
CLASSIFICATION; MOLECULAR-GENETICS; CELL DEVELOPMENT; COMPETING RISK;
RECEPTOR
AB Gene expression profiling of 207 uniformly treated children with high-risk B-progenitor acute lymphoblastic leukemia revealed 29 of 207 cases (14%) with markedly elevated expression of CRLF2 (cytokine receptor-like factor 2). Each of the 29 cases harbored a genomic rearrangement of CRLF2: 18 of 29 (62%) had a translocation of the immunoglobulin heavy chain gene IGH@ on 14q32 to CRLF2 in the pseudoautosomal region 1 of Xp22.3/Yp11.3, whereas 10 (34%) cases had a 320-kb interstitial deletion centromeric of CRLF2, resulting in a P2RY8-CRLF2 fusion. One case had both IGH@-CRLF2 and P2RY8-CRLF2, and another had a novel CRLF2 rearrangement. Only 2 of 29 cases were Down syndrome. CRLF2 rearrangements were significantly associated with activating mutations of JAK1 or JAK2, deletion or mutation of IKZF1, and Hispanic/Latino ethnicity (Fisher exact test, P < .001 for each). Within this cohort, patients with CRLF2 rearrangements had extremely poor treatment outcomes compared with those without CRLF2 rearrangements (35.3% vs 71.3% relapse-free survival at 4 years; P < .001). Together, these observations suggest that activation of CRLF2 expression, mutation of JAK kinases, and alterations of IKZF1 cooperate to promote B-cell leukemogenesis and identify these pathways as important therapeutic targets in this disease. This trial was registered at www.clinicaltrials.gov as #NCT00005603. (Blood. 2010;115(26):5312-5321)
C1 [Harvey, Richard C.; Chen, I-Ming; Wharton, Walker; Kang, Huining; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Chen, I-Ming; Wharton, Walker; Kang, Huining; Willman, Cheryl L.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Chen, I-Ming; Wharton, Walker; Kang, Huining; Willman, Cheryl L.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Chen, I-Ming; Carroll, Andrew J.; Carroll, William L.; Devidas, Meenakshi; Bowman, W. Paul; Camitta, Bruce M.; Reaman, Gregory H.; Hunger, Stephen P.; Willman, Cheryl L.] Childrens Oncol Grp, Arcadia, CA USA.
[Mullighan, Charles G.; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Mikhail, Fady M.; Carroll, Andrew J.] Univ Alabama, Dept Genet, Birmingham, AL USA.
[Liu, Wei] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA.
[Dobbin, Kevin K.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Carroll, William L.] NYU, Med Ctr, Dept Pediat, New York, NY 10003 USA.
[Carroll, William L.] NYU, Med Ctr, Dept Hematol, New York, NY 10003 USA.
[Carroll, William L.] NYU, Med Ctr, Dept Oncol, New York, NY 10003 USA.
[Carroll, William L.] NYU, Med Ctr, Ctr Canc, New York, NY 10003 USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA.
[Bowman, W. Paul] Cook Childrens Med Ctr, Ft Worth, TX USA.
[Camitta, Bruce M.] Med Coll Wisconsin, Dept Pediat Hematol Oncol & Transplantat, Milwaukee, WI 53226 USA.
[Reaman, Gregory H.] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA.
[Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Childrens Hosp, Dept Pediat, Aurora, CO USA.
[Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Ctr Canc, Aurora, CO USA.
RP Willman, CL (reprint author), Univ New Mexico, Ctr Canc, MSC08 4630 1, Albuquerque, NM 87131 USA.
EM charles.mullighan@stjude.org; hunger.stephen@tchden.org;
cwillman@salud.unm.edu
OI Harvey, Richard/0000-0002-4904-9767; Mullighan,
Charles/0000-0002-1871-1850
FU National Institutes of Health [U01 CA114762]; National Cancer Institute
[U10CA98543]; American Lebanese Syrian Associated Charities; National
Childhood Cancer Foundation; Leukemia & Lymphoma Society [7388-06]; COG
[U24 CA114766, CA114766]; Pew Scholar award
FX This work was supported by National Institutes of Health Department of
Health and Human Services: National Cancer Institute Strategic
Partnerships to Evaluate Cancer Gene Signatures Program National Cancer
Institute (U01 CA114762; principal investigator, C.L.W.) and National
Cancer Institute (U10CA98543, supporting the COG and Statistical Center,
principal investigator, G.H.R.), the American Lebanese Syrian Associated
Charities (J.R.D.), the National Childhood Cancer Foundation, COG (cell
banking grant U24 CA114766, G.H.R.), and a Leukemia & Lymphoma Society
Specialized Center of Research (program grant 7388-06, principal
investigator, C.L.W.). This work was supported in part by grants to the
COG (CA114766 and a supplement to that grant for the Therapeutically
Applicable Research to Generate Effective Targets project) and a Pew
Scholar award (C.G.M.). S.P.H. is the Ergen Family Chair in Pediatric
Cancer. Optimization of FISH probes was performed at the University of
New Mexico Cancer Center Fluorescence Microscopy Facility (supported as
detailed on the webpage:
http://hsc.unm.edu/crtc/microscopy/Facility.html).
NR 42
TC 202
Z9 209
U1 2
U2 9
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 JUL 1
PY 2010
VL 115
IS 26
BP 5312
EP 5321
DI 10.1182/blood-2009-09-245944
PG 10
WC Hematology
SC Hematology
GA 619MV
UT WOS:000279435200007
PM 20139093
ER
PT J
AU Rahimi, Z
Mozafari, H
Shahriari-Ahmadi, A
Alimogaddam, K
Ghavamzadeh, A
Aznab, M
Mansouri, K
Rezaei, M
Parsian, A
AF Rahimi, Zohreh
Mozafari, Hadi
Shahriari-Ahmadi, Ali
Alimogaddam, Kamran
Ghavamzadeh, Ardeshir
Aznab, Mozafar
Mansouri, Kamran
Rezaei, Mansour
Parsian, Abbas
TI Deep venous thrombosis and thrombophilic mutations in western Iran:
association with factor V Leiden
SO BLOOD COAGULATION & FIBRINOLYSIS
LA English
DT Article
DE deep venous thrombosis; factor V Leiden; methylenetetrahydrofolate
reductase c.677C > T; prevalence; prothrombin g.20210G > A; western Iran
ID METHYLENETETRAHYDROFOLATE-REDUCTASE GENE; PLASMA PROTHROMBIN LEVELS;
COAGULATION-FACTOR-V; ACTIVATED PROTEIN-C; VEIN THROMBOSIS; G20210A
MUTATION; COMMON MUTATION; RISK-FACTORS; THROMBOEMBOLISM; PREVALENCE
AB The aim of present study was to investigate the prevalence of factor V Leiden (FVL) c.1691G>A, prothrombin g. 20210G>A and methylenetetrahydrofolate reductase (MTHFR) c.677C>T in deep vein thrombosis (DVT) patients and their possible association with DVT in western Iran. Eighty DVT patients with the mean age of 42.07 +/- 13.0 years including 44 women and 36 men and 100 sex-matched healthy individuals with the mean age of 37.63 +/- 13.3 years from Kermanshah Province of Iran with ethnic background of Kurd were studied for FVL c.1691G>A, prothrombin g. 20210G>A and MTHFR c.677C>T by PCR-restriction fragment length polymorphism (RFLP) method using MnlI, HindIII and HinfI restriction enzymes, respectively. Prevalence of FVL was 11.4% in patients and 2% in control group. A significant association was found between FVL mutation and DVT with odds ratio (OR) of 6.3 [95% confidence interval (CI) U1.32-30.05; P = 0.012]. The prevalence of prothrombin g. 20210G>A variant in patients (3.8%) was nonsignificantly higher than control individuals (1.0%; OR 3.8; 95% CI = 0.39-37.81; P = 0.32). The prevalence of MTHFR c.677C>T in patients was 38.7% that was not statistically different from control group (44% P = 0.12). Venous thrombosis in legs was the most frequent clinical manifestation (n = 75), corresponding to 93.8% of the thromboembolism, followed by pulmonary thromboembolism (6.2%). We have, for the first time, determined the prevalence of inherited thrombophilia in a homogenous ethnic group of DVT patients and shown that FVL may be a risk factor for DVT in western Iran. Blood Coagul Fibrinolysis 21:385-388 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Rahimi, Zohreh; Mozafari, Hadi; Mansouri, Kamran] Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Kermanshah, Iran.
[Rahimi, Zohreh] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran.
[Shahriari-Ahmadi, Ali; Aznab, Mozafar] Kermanshah Univ Med Sci, Sch Med, Dept Hematol & Oncol, Kermanshah, Iran.
[Alimogaddam, Kamran; Ghavamzadeh, Ardeshir] Univ Tehran Med Sci, Shariati Hosp, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran.
[Rezaei, Mansour] Kermanshah Univ Med Sci, Sch Med, Dept Biostat, Kermanshah, Iran.
[Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA.
RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, POB 67148-69914,Daneshgah Ave, Kermanshah, Iran.
EM zrahimi@kums.ac.ir
OI Rahimi, Zohreh/0000-0001-7589-3307; Rezaei, Mansour/0000-0002-6446-7289
NR 23
TC 12
Z9 14
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0957-5235
J9 BLOOD COAGUL FIBRIN
JI Blood Coagul. Fibrinolysis
PD JUL
PY 2010
VL 21
IS 5
BP 385
EP 388
DI 10.1097/MBC.0b013e328330e69a
PG 4
WC Hematology
SC Hematology
GA 619AZ
UT WOS:000279400400001
PM 20479641
ER
PT J
AU Shimamura, A
Alter, BP
AF Shimamura, Akiko
Alter, Blanche P.
TI Pathophysiology and management of inherited bone marrow failure
syndromes (vol 24, pg 101, 2010)
SO BLOOD REVIEWS
LA English
DT Correction
C1 [Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Shimamura, Akiko] Seattle Childrens Hosp, Seattle, WA USA.
[Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Shimamura, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA.
EM ashimamu@fhcrc.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0268-960X
J9 BLOOD REV
JI Blood Rev.
PD JUL-SEP
PY 2010
VL 24
IS 4-5
BP 201
EP 201
DI 10.1016/j.blre.2010.06.005
PG 1
WC Hematology
SC Hematology
GA 643SC
UT WOS:000281317900007
ER
PT J
AU Makareeva, E
Han, S
Vera, J
Sackett, D
Holmbeck, K
McBride, DJ
Phillips, CL
Schwarze, U
Pace, JM
Byer, PH
Visse, R
Nagase, H
Leikin, S
AF Makareeva, E.
Han, S.
Vera, J.
Sackett, D.
Holmbeck, K.
McBride, D. J.
Phillips, C. L.
Schwarze, U.
Pace, J. M.
Byer, P. H.
Visse, R.
Nagase, H.
Leikin, S.
TI Cancer cells secrete MMP-resistant isoform of type I collagen
SO BONE
LA English
DT Meeting Abstract
CT 9th International Meeting on Cancer Induced Bone Disease
CY OCT 28-31, 2009
CL Arlington, VA
ID TUMOR INVASION; MATRIX METALLOPROTEINASES; BIOPSY FRAGMENTS; METASTASIS
C1 [Makareeva, E.; Han, S.; Vera, J.; Sackett, D.; Holmbeck, K.; Leikin, S.] NIH, Bethesda, MD 20892 USA.
[McBride, D. J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Phillips, C. L.] Univ Missouri, Columbia, MO USA.
[Schwarze, U.; Pace, J. M.; Byer, P. H.] Univ Washington, Seattle, WA 98195 USA.
[Visse, R.; Nagase, H.] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol, London, England.
NR 6
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2010
VL 47
SU 2
BP S297
EP S297
DI 10.1016/j.bone.2010.01.243
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 632SV
UT WOS:000280449200069
ER
PT J
AU Yin, J
Zhang, L
Quadri, R
Munasinghe, J
Kelly, K
AF Yin, J.
Zhang, L.
Quadri, R.
Munasinghe, J.
Kelly, K.
TI AZD2171 inhibits the development and progression of bone and brain
metastasis in a mouse metastasis model
SO BONE
LA English
DT Meeting Abstract
CT 9th International Meeting on Cancer Induced Bone Disease
CY OCT 28-31, 2009
CL Arlington, VA
C1 [Yin, J.; Zhang, L.; Quadri, R.; Munasinghe, J.; Kelly, K.] NCI, 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 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2010
VL 47
SU 2
BP S279
EP S280
DI 10.1016/j.bone.2010.01.353
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 632SV
UT WOS:000280449200035
ER
PT J
AU Chung, CY
Licznerski, P
Alavian, KN
Simeone, A
Lin, ZC
Martin, E
Vance, J
Isacson, O
AF Chung, Chee Yeun
Licznerski, Pawel
Alavian, Kambiz N.
Simeone, Antonio
Lin, Zhicheng
Martin, Eden
Vance, Jeffery
Isacson, Ole
TI The transcription factor orthodenticle homeobox 2 influences axonal
projections and vulnerability of midbrain dopaminergic neurons
SO BRAIN
LA English
DT Article
DE axon; protection; Parkinson's disease; neuropeptides; transcription
factor
ID CYCLASE-ACTIVATING POLYPEPTIDE; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE;
VENTRAL MIDBRAIN; PACAP; DIFFERENTIATION; EXPRESSION; BRAIN
AB Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease. Here, we demonstrate elevated expression of the transcription factor orthodenticle homeobox 2 in A10 dopaminergic neurons of embryonic and adult mouse, primate and human midbrain. Overexpression of orthodenticle homeobox 2 using lentivirus increased levels of known A10 elevated genes, including neuropilin 1, neuropilin 2, slit2 and adenylyl cyclase-activating peptide in both MN9D cells and ventral mesencephalic cultures, whereas knockdown of endogenous orthodenticle homeobox 2 levels via short hairpin RNA reduced expression of these genes in ventral mesencephalic cultures. Lack of orthodenticle homeobox 2 in the ventral mesencephalon of orthodenticle homeobox 2 conditional knockout mice caused a reduction of midbrain dopaminergic neurons and selective loss of A10 dopaminergic projections. Orthodenticle homeobox 2 overexpression protected dopaminergic neurons in ventral mesencephalic cultures from Parkinson's disease-relevant toxin, 1-methyl-4-phenylpyridinium, whereas downregulation of orthodenticle homeobox 2 using short hairpin RNA increased their susceptibility. These results show that orthodenticle homeobox 2 is important for establishing subgroup phenotypes of post-mitotic midbrain dopaminergic neurons and may alter neuronal vulnerability.
C1 [Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Isacson, Ole] Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA.
[Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Isacson, Ole] Harvard Univ, McLean Hosp, NINDS Udall Ctr Excellence Parkinsons Dis Res, Belmont, MA 02478 USA.
[Chung, Chee Yeun; Isacson, Ole] Harvard NeuroDiscovery Ctr, Boston, MA 02114 USA.
[Simeone, Antonio] SEMM European Sch Mol Med Naples Site, I-80145 Naples, Italy.
[Simeone, Antonio] CEINGE Biotecnol Avanzate, Naples, Italy.
[Simeone, Antonio] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy.
[Lin, Zhicheng] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA.
[Lin, Zhicheng] McLean Hosp, Mailman Neurosci Res Ctr, Belmont, MA 02478 USA.
[Martin, Eden; Vance, Jeffery] Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA.
[Martin, Eden; Vance, Jeffery] Univ Miami, NINDS Udall Ctr Excellence Parkinsons Dis Res, Miami, FL 33136 USA.
RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, 115 Mill St, Belmont, MA 02478 USA.
EM isacson@hms.harvard.edu
RI Alavian, Kambiz/D-7720-2012;
OI Alavian, Kambiz/0000-0002-0653-3057
FU NIH/NINDS [P50 (NS39793)]; Parkinson's Disease Udall Research Centres of
Excellence to McLean/Harvard Medical School; Michael Stern Foundation
for Parkinson's Disease Research; Orchard Foundation; Consolidated
Anti-Aging Foundation; Harold and Ronna Cooper Family; Stem Cell Project
of Fondazione Roma, Rome Italy; National Institutes of Health [NS39764]
FX This study was conducted at McLean Hospital. NIH/NINDS P50 (NS39793) to
O.I.; Parkinson's Disease Udall Research Centres of Excellence to
McLean/Harvard Medical School, the Michael Stern Foundation for
Parkinson's Disease Research, the Orchard Foundation, the Consolidated
Anti-Aging Foundation, Harold and Ronna Cooper Family; Stem Cell Project
of Fondazione Roma, Rome Italy to A. S.; National Institutes of Health
Grant NS39764.
NR 22
TC 26
Z9 27
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2010
VL 133
BP 2022
EP 2031
DI 10.1093/brain/awq142
PN 7
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 620BL
UT WOS:000279473900015
PM 20573704
ER
PT J
AU Kasperaviciute, D
Catarino, CB
Heinzen, EL
Depondt, C
Cavalleri, GL
Caboclo, LO
Tate, SK
Jamnadas-Khoda, J
Chinthapalli, K
Clayton, LMS
Shianna, KV
Radtke, RA
Mikati, MA
Gallentine, WB
Husain, AM
Alhusaini, S
Leppert, D
Middleton, LT
Gibson, RA
Johnson, MR
Matthews, PM
Hosford, D
Heuser, K
Amos, L
Ortega, M
Zumsteg, D
Wieser, HG
Steinhoff, BJ
Krarmer, G
Hansen, J
Dorn, T
Kantanen, AM
Gjerstad, L
Peuralinna, T
Hernandez, DG
Eriksson, KJ
Kalviainen, RK
Doherty, CP
Wood, NW
Pandolfo, M
Duncan, JS
Sander, JW
Delanty, N
Goldstein, DB
Sisodiya, SM
AF Kasperaviciute, Dalia
Catarino, Claudia B.
Heinzen, Erin L.
Depondt, Chantal
Cavalleri, Gianpiero L.
Caboclo, Luis O.
Tate, Sarah K.
Jamnadas-Khoda, Jenny
Chinthapalli, Krishna
Clayton, Lisa M. S.
Shianna, Kevin V.
Radtke, Rodney A.
Mikati, Mohamad A.
Gallentine, William B.
Husain, Aatif M.
Alhusaini, Saud
Leppert, David
Middleton, Lefkos T.
Gibson, Rachel A.
Johnson, Michael R.
Matthews, Paul M.
Hosford, David
Heuser, Kjell
Amos, Leslie
Ortega, Marcos
Zumsteg, Dominik
Wieser, Heinz-Gregor
Steinhoff, Bernhard J.
Kraermer, Guernter
Hansen, Joerg
Dorn, Thomas
Kantanen, Anne-Mari
Gjerstad, Leif
Peuralinna, Terhi
Hernandez, Dena G.
Eriksson, Kai J.
Kalviainen, Reetta K.
Doherty, Colin P.
Wood, Nicholas W.
Pandolfo, Massimo
Duncan, John S.
Sander, Josemir W.
Delanty, Norman
Goldstein, David B.
Sisodiya, Sanjay M.
TI Common genetic variation and susceptibility to partial epilepsies: a
genome-wide association study
SO BRAIN
LA English
DT Article
DE partial epilepsy; genome-wide association; genetics; common variants
ID ENVIRONMENTAL-FACTORS; 16P13.11 PREDISPOSE; POPULATION; LOCI; TWIN;
METAANALYSIS; ETIOLOGY; SEIZURES; DISEASES; LINKAGE
AB Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio < 1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.
C1 [Kasperaviciute, Dalia; Catarino, Claudia B.; Caboclo, Luis O.; Tate, Sarah K.; Jamnadas-Khoda, Jenny; Chinthapalli, Krishna; Clayton, Lisa M. S.; Duncan, John S.; Sander, Josemir W.; Sisodiya, Sanjay M.] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England.
[Catarino, Claudia B.; Duncan, John S.; Sander, Josemir W.; Sisodiya, Sanjay M.] Natl Soc Epilepsy, Gerrards Cross SL9 0RJ, Bucks, England.
[Heinzen, Erin L.; Shianna, Kevin V.; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA.
[Depondt, Chantal; Pandolfo, Massimo] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, B-1070 Brussels, Belgium.
[Cavalleri, Gianpiero L.; Alhusaini, Saud; Delanty, Norman] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Radtke, Rodney A.; Husain, Aatif M.] Duke Univ, Dept Med Neurol, Sch Med, Durham, NC 27710 USA.
[Mikati, Mohamad A.; Gallentine, William B.] Duke Univ, Div Paediat Neurol, Sch Med, Durham, NC 27710 USA.
[Leppert, David; Middleton, Lefkos T.; Gibson, Rachel A.; Matthews, Paul M.; Hosford, David; Amos, Leslie] GlaxoSmithKline Inc, Drug Discovery, Div Genet, Res Triangle Pk, NC 27709 USA.
[Leppert, David] Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
[Middleton, Lefkos T.; Johnson, Michael R.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Clin Neurosci, London W12 0NN, England.
[Heuser, Kjell; Gjerstad, Leif] Oslo Univ Hosp, Rikshosp, Dept Neurol, Oslo, Norway.
[Ortega, Marcos; Zumsteg, Dominik; Wieser, Heinz-Gregor; Duncan, John S.] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Steinhoff, Bernhard J.] Kork Epilepsy Ctr, Kehl, Germany.
[Kraermer, Guernter; Hansen, Joerg; Dorn, Thomas] Swiss Epilepsy Ctr, CH-8008 Zurich, Switzerland.
[Kantanen, Anne-Mari; Kalviainen, Reetta K.] Kuopio Univ Hosp, Kuopio Epilepsy Ctr, SF-70210 Kuopio, Finland.
[Gjerstad, Leif] Univ Oslo, Fac Med, Oslo, Norway.
[Peuralinna, Terhi] Univ Helsinki, Helsinki, Finland.
[Peuralinna, Terhi] Univ Helsinki, Dept Neurol, Cent Hosp, Helsinki, Finland.
[Hernandez, Dena G.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Eriksson, Kai J.] Univ Tampere, Tampere Univ Hosp, Paediat Neurol Unit, FIN-33101 Tampere, Finland.
[Eriksson, Kai J.] Univ Tampere, Paediat Res Ctr, FIN-33101 Tampere, Finland.
[Kalviainen, Reetta K.] Univ Eastern Finland, Inst Clin Med, Dept Neurol, Kuopio, Finland.
[Doherty, Colin P.] St James Hosp Dublin, Dept Neurol, Dublin, Ireland.
[Wood, Nicholas W.] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Sander, Josemir W.] Netherlands Fdn, Epilepsy Inst, SEIN, NL-2103 SW Heemstede, Netherlands.
RP Sisodiya, SM (reprint author), UCL Inst Neurol, Dept Clin & Expt Epilepsy, Queen Sq, London WC1N 3BG, England.
EM d.goldstein@duke.edu; s.sisodiya@ion.ucl.ac.uk
RI Kasperaviciute, Dalia/D-1493-2009; Chinthapalli, Vamsi/A-8759-2011;
Catarino, Claudia/A-7719-2010; Sander, Josemir/C-1576-2008; Cavalleri,
Gianpiero/A-6632-2010; Delanty, Norman/F-8756-2011; Caboclo, Luis
Otavio/G-6880-2012; Wood, Nicholas/C-2505-2009
OI Delaney, Norman/0000-0002-3953-9842; Matthews, Paul
M/0000-0002-1619-8328; Catarino, Claudia/0000-0002-6528-7570; Sander,
Josemir/0000-0001-6041-9661; Cavalleri, Gianpiero/0000-0002-9802-0506;
Wood, Nicholas/0000-0002-9500-3348
FU Medical Research Council [G0400126]; Wellcome Trust [084730]; UCLH CRDC
[F136]; National Institute for Health Research [08-08-SCC]; National
Society for Epilepsy; Department of Health's NIHR Biomedical Research
Centres; Irish patient cohort was supported by the Irish Higher
Education Authority [PRTLI3]; Science Foundation Ireland
[08/RFP/GEN1538]; GlaxoSmithKline; Funds National de la Recherche
Scientifique [FC 63574/3.4.620.06 F]; Fondation Erasme; Universite Libre
de Bruxelles; Muscular Dystrophy Association, USA; Irish Institute of
Clinical Neurosciences; National Institutes of Health, USA
FX This work was supported by grants from the Medical Research Council
(G0400126); The Wellcome Trust (084730); UCLH CRDC (F136); the National
Institute for Health Research (08-08-SCC); the National Society for
Epilepsy. This work was partly undertaken at UCLH/UCL, which received a
proportion of funding from the Department of Health's NIHR Biomedical
Research Centres funding scheme; The collection of the Irish patient
cohort was supported by the Irish Higher Education Authority Programme
for Research in Third Level Institutions (PRTLI3); phenotyping by a
Science Foundation Ireland Research Frontiers Programme award
(08/RFP/GEN1538); GlaxoSmithKline funded the recruitment and phenotypic
data collection of the GenEpA Consortium samples used in this study and
contributed to the genotyping costs associated with their study; the
collection of the Belgian patients was supported by the Funds National
de la Recherche Scientifique, grant no. FC 63574/3.4.620.06 F and the
Fondation Erasme, Universite Libre de Bruxelles; Funding support for
Study of Irish Amyotrophic Lateral Sclerosis was provided by Muscular
Dystrophy Association, USA; Irish Institute of Clinical Neurosciences
Travel Award; and National Institutes of Health, USA and the genotyping
of samples was provided by the National Institute of Neurological
Disorders and Stroke (NINDS). The dataset used for the analyses
described in this manuscript was obtained from the NINDS Database found
at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number
phs000127.v1.p1.
NR 41
TC 72
Z9 73
U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2010
VL 133
BP 2136
EP 2147
DI 10.1093/brain/awq130
PN 7
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 620BL
UT WOS:000279473900024
PM 20522523
ER
PT J
AU Murrow, LM
Garimella, SV
Jones, TL
Caplen, NJ
Lipkowitz, S
AF Murrow, Lyndsay M.
Garimella, Sireesha V.
Jones, Tamara L.
Caplen, Natasha J.
Lipkowitz, Stanley
TI Identification of WEE1 as a potential molecular target in cancer cells
by RNAi screening of the human tyrosine kinome
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE RNAi screen; Breast cancer; Tyrosine kinase; WEE1; Apoptosis
ID NEGATIVE BREAST-CANCER; DNA-DAMAGE; GENE-EXPRESSION; PROTEIN-KINASES;
CHECKPOINT; APOPTOSIS; CHK1; INHIBITORS; PD0166285; P53
AB Breast cancers can be classified into those that express the estrogen (ER) and progesterone (PR) receptors, those with ERBB2 (HER-2/Neu) amplification, and those without expression of ER, PR, or amplification of ERBB2 (referred to as triple-negative or basal-like breast cancer). In order to identify potential molecular targets in breast cancer, we performed a synthetic siRNA-mediated RNAi screen of the human tyrosine kinome. A primary RNAi screen conducted in the triple-negative/basal-like breast cancer cell line MDA-MB231 followed by secondary RNAi screens and further studies in this cell line and two additional triple-negative/basal-like breast cancer cell lines, BT20 and HCC1937, identified the G2/M checkpoint protein, WEE1, as a potential therapeutic target. Similar sensitivity to WEE1 inhibition was observed in cell lines from all subtypes of breast cancer. RNAi-mediated silencing or small compound inhibition of WEE1 in breast cancer cell lines resulted in an increase in gamma H2AX levels, arrest in the S-phase of the cell cycle, and a significant decrease in cell proliferation. WEE1-inhibited cells underwent apoptosis as demonstrated by positive Annexin V staining, increased sub-G1 DNA content, apoptotic morphology, caspase activation, and rescue by the pan-caspase inhibitor, Z-VAD-FMK. In contrast, the non-transformed mammary epithelial cell line, MCF10A, did not exhibit any of these downstream effects following WEE1 silencing or inhibition. These results identify WEE1 as a potential molecular target in breast cancer.
C1 [Murrow, Lyndsay M.; Garimella, Sireesha V.; Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jones, Tamara L.; Caplen, Natasha J.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lipkowitz, S (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM lipkowis@mail.nih.gov
RI Caplen, Natasha/H-2768-2016
OI Caplen, Natasha/0000-0002-0001-9460
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Marion Nau for critical reading of this manuscript. Financial
Support This research was supported by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 40
TC 45
Z9 48
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2010
VL 122
IS 2
BP 347
EP 357
DI 10.1007/s10549-009-0571-2
PG 11
WC Oncology
SC Oncology
GA 611JF
UT WOS:000278810700005
PM 19821025
ER
PT J
AU Munson, JC
Kreider, M
Chen, Z
Christie, JD
Kimmel, SE
AF Munson, Jeffrey C.
Kreider, Maryl
Chen, Zhen
Christie, Jason D.
Kimmel, Stephen E.
TI Effect of treatment guidelines on the initial management of idiopathic
pulmonary fibrosis
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE corticosteroids; idiopathic pulmonary fibrosis; pharmacoepidemiology;
treatment guidelines
ID CONTROLLED TRIAL; ALVEOLITIS; CYCLOPHOSPHAMIDE; PREDNISONE; SURVIVAL;
THERAPY; DISEASE; RISK; UK
AB center dot Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease with no known aetiology and no proven treatment. Despite the absence of efficacy data, many physicians treat IPF with corticosteroids either as monotherapy or in combination with a cytotoxic agent.
center dot Specialty society guidelines published in 1999 and 2000 recognize that treatment may not be appropriate for all patients with IPF, but recommend that if treatment is to be initiated, a combination of corticosteroids with a cytotoxic agent is preferred over corticosteroids alone.
center dot It is not known how the use of corticosteroids and cytotoxic agents in the treatment of IPF has changed over time and whether published guidelines have altered prescribing practices.
WHAT THIS STUDY ADDS
center dot The results of this study demonstrate a modest but statistically significant reduction in the overall use of corticosteroids since the publication of treatment guidelines. At the same time, there was a more pronounced increase in the combined use of corticosteroids and cytotoxic agents consistent with recommendations.
center dot Even with the increase in the use of combination therapy, corticosteroid monotherapy remained the most commonly prescribed regimen among treated patients.
center dot Given the lack of established benefit and the risks associated with corticosteroid therapy, the reasons for the continued use of corticosteroid monotherapy in the majority of treated patients warrant further investigation.
AIMS
To assess the impact of specialty society guidelines on the use of corticosteroids and cytotoxic agents in the initial management of patients with idiopathic pulmonary fibrosis.
METHODS
A retrospective cohort study of 941 patients with an incident diagnosis of IPF was conducted using a large medical records database. The primary outcome was a new prescription for corticosteroids with or without a cytotoxic agent within 30 days of diagnosis. The primary exposure was whether diagnosis occurred before or after the publication of treatment guidelines. Logistic regression was used to control for changes in population demographics and disease characteristics across time.
RESULTS
In total, 187 patients (19.9%) received a new corticosteroid prescription within 30 days of diagnosis. Fewer patients received corticosteroids after the publication of guidelines (22.2% vs. 17.7%; adjusted OR for steroid use after the publication of guidelines 0.65, 95% confidence interval 0.46, 0.92, P = 0.014). Among the 187 patients treated with corticosteroids, 22 (11.8%) also received a cytotoxic agent. The use of cytotoxic agents among users of corticosteroids increased significantly after the publication of guidelines (5.1% vs. 19.3%) with a fully adjusted OR = 4.71 (95% CI 1.56, 14.21, P = 0.006).
CONCLUSIONS
Since the publication of treatment guidelines, there has been a small reduction in the overall use of corticosteroids. Consistent with these guidelines, the use of cytotoxic agents among those prescribed corticosteroids has increased significantly; however, the use of these agents remains uncommon.
C1 [Munson, Jeffrey C.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Munson, Jeffrey C.; Kreider, Maryl; Christie, Jason D.] Hosp Univ Penn, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA.
[Chen, Zhen] NIH, Bethesda, MD 20892 USA.
[Kimmel, Stephen E.] Hosp Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
RP Munson, JC (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 718 Blockley Hall,Guardian Dr, Philadelphia, PA 19104 USA.
EM jeffrey.munson@uphs.upenn.edu
FU Gilead Sciences Inc, Seattle WA; National Institutes of Health
[T32-GM075766-02, UL1-RR024134]; Ruth Kirchstein National Research
Service [1F32-HL092741-01]
FX JM, ZC, and JC have no competing interests to declare. MK is the PI on a
clinical trial sponsored by Gilead Sciences Inc, Seattle WA. SK has
performed research and done consulting work funded by various
pharmaceutical companies, none directly related to the topic of this
manuscript.; During the conduct of this study, JM received support from
the National Institutes of Health in the form of an institutional
training grant (T32-GM075766-02) and a Ruth Kirchstein National Research
Service Award (1F32-HL092741-01). This study was also supported in part
by a Clinical and Translational Science Award from the National
Institutes of Health (UL1-RR024134).
NR 28
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0306-5251
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD JUL
PY 2010
VL 70
IS 1
BP 118
EP 125
DI 10.1111/j.1365-2125.2010.03670.x
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 609GK
UT WOS:000278643800015
PM 20642554
ER
PT J
AU Aliyu, ZY
Suleiman, A
Attah, E
Mamman, AI
Babadoko, A
Nouraie, M
Mendelsohn, L
Kato, GJ
Gordeuk, VR
Gladwin, MT
AF Aliyu, Zakari Y.
Suleiman, Aisha
Attah, Ester
Mamman, Aisha I.
Babadoko, Aliyu
Nouraie, Mehdi
Mendelsohn, Laurel
Kato, Gregory J.
Gordeuk, Victor R.
Gladwin, Mark T.
TI NT-proBNP as a marker of cardiopulmonary status in sickle cell anaemia
in Africa
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE sickle cell disease; N-terminal pro-brain natriuretic peptide;
six-minute walk; haemolysis; Africa
ID BRAIN NATRIURETIC PEPTIDE; 6-MINUTE WALK TEST; PRIMARY
PULMONARY-HYPERTENSION; LEFT-VENTRICULAR DYSFUNCTION; STANDARDS
COMMITTEE; OF-ECHOCARDIOGRAPHY; RISK-FACTOR; DISEASE; DEATH;
RECOMMENDATIONS
AB P>N-terminal (NT) pro-brain natriuretic peptide (proBNP) >= 160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross-sectional study at Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria, we studied 133 hydroxycarbamide-naive Nigerian sickle cell anaemia patients aged 18-52 years at steady-state and 65 healthy controls. Twenty-six percent of patients versus 5% of controls had NT-proBNP >= 160 ng/l (P = 0 center dot 0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT-proBNP. After adjustment for haemoglobin concentration, elevated NT-proBNP concentration was associated with an estimated 7 center dot 8-fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1 center dot 5-32 center dot 6; P = 0 center dot 005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5 center dot 6-fold increase in the odds of functional impairment (95% confidence interval 1 center dot 5-21 center dot 0; P = 0 center dot 011). In conclusion, NT-proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.
C1 [Aliyu, Zakari Y.; Nouraie, Mehdi; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20001 USA.
[Aliyu, Zakari Y.] Taraba State Specialist Hosp, Jalingo, Nigeria.
[Suleiman, Aisha; Attah, Ester; Mamman, Aisha I.; Babadoko, Aliyu] Ahmadu Bello Univ, Teaching Hosp, Shika Zaria, Nigeria.
[Mendelsohn, Laurel; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 1840 7th St NW, Washington, DC 20001 USA.
EM vgordeuk@howard.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL005075-04, ZIA HL005075-05]; NCRR NIH HHS [M01
RR010284-135214]; NHLBI NIH HHS [1 R01 HL079912-03, 2 R25 HL003679-08,
R01 HL079912, R01 HL079912-04, R25 HL003679, R25 HL003679-10, U54
HL090508, U54 HL090508-02S2]
NR 23
TC 6
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2010
VL 150
IS 1
BP 102
EP 107
DI 10.1111/j.1365-2141.2010.08195.x
PG 6
WC Hematology
SC Hematology
GA 608XD
UT WOS:000278618400012
PM 20408845
ER
PT J
AU Alter, BP
Giri, N
Savage, SA
Peters, JA
Loud, JT
Leathwood, L
Carr, AG
Greene, MH
Rosenberg, PS
AF Alter, Blanche P.
Giri, Neelam
Savage, Sharon A.
Peters, June A.
Loud, Jennifer T.
Leathwood, Lisa
Carr, Ann G.
Greene, Mark H.
Rosenberg, Philip S.
TI Malignancies and survival patterns in the National Cancer Institute
inherited bone marrow failure syndromes cohort study
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE bone marrow failure; Fanconi anaemia; dyskeratosis congenita; leukaemia;
solid tumours
ID DIAMOND-BLACKFAN ANEMIA; FANCONI-ANEMIA; DYSKERATOSIS-CONGENITA;
TELOMERE LENGTH; MUTATIONS; REGISTRY; HEAD
AB P>Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST). The natural history of FA is well characterised; hazard rates in the other syndromes have not yet been quantified. An open cohort was established at the National Cancer Institute (NCI) in 2002. Patients enrolled prior to December, 2007 were followed up to December, 2008. Diagnoses were confirmed with standard tests. Age-associated risks of adverse events were calculated. Most patients in each syndrome survived to young adulthood. Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients. The NCI cohort provides the first direct quantitative comparison of timing and magnitude of cancer risk in the IBMFS. The findings demonstrate that both FA and DC are major cancer susceptibility syndromes. The IBMFS, historically considered paediatric disorders, have important management implications for physicians treating adult patients.
C1 [Alter, Blanche P.; Giri, Neelam; Savage, Sharon A.; Peters, June A.; Loud, Jennifer T.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Leathwood, Lisa; Carr, Ann G.] WESTAT Corp, Rockville, MD 20850 USA.
RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S Room 7020, Rockville, MD 20852 USA.
EM alterb@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU National Institute of Health (NIH) [N02-CP-11019, N02-CP-65504,
N02-CP-65501, N02-CP-31003]; National Cancer Institute
FX We are grateful to all the patients who participated in the National
Cancer Institute inherited bone marrow failure syndromes cohort, to the
physicians who referred the patients, and to our colleagues in the
Clinical Genetics Branch of the NCI, and the subspecialty clinics at the
National Institutes of Health for their evaluations of the patients.
Study management was provided by Sara Glashofer of Westat (Rockville,
MD), through NIH contracts N02-CP-11019, N02-CP-65504, and N02-CP-65501.
Observed-to-expected ratios were provided by Jeremy Miller at
Information Management Systems (Silver Spring, MD), through NIH contract
N02-CP-31003. This work was supported in part by the Intramural Program
of the National Institutes of Health and the National Cancer Institute.
NR 27
TC 116
Z9 117
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2010
VL 150
IS 2
BP 179
EP 188
DI 10.1111/j.1365-2141.2010.08212.x
PG 10
WC Hematology
SC Hematology
GA 619OD
UT WOS:000279438600006
PM 20507306
ER
PT J
AU Rosenberg, PS
Zeidler, C
Bolyard, AA
Alter, BP
Bonilla, MA
Boxer, LA
Dror, Y
Kinsey, S
Link, DC
Newburger, PE
Shimamura, A
Welte, K
Dale, DC
AF Rosenberg, Philip S.
Zeidler, Cornelia
Bolyard, Audrey A.
Alter, Blanche P.
Bonilla, Mary A.
Boxer, Laurence A.
Dror, Yigal
Kinsey, Sally
Link, Daniel C.
Newburger, Peter E.
Shimamura, Akiko
Welte, Karl
Dale, David C.
TI Stable long-term risk of leukaemia in patients with severe congenital
neutropenia maintained on G-CSF therapy
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE severe congenital neutropenia; acute myeloid leukaemia; myelodysplastic
syndromes; granulocyte colony-stimulating factor
ID CANCER
AB P>In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. Long-term, the annual risk of MDS/AML attained a plateau (2 center dot 3%/year after 10 years). This risk now appears similar to, rather than higher than, the risk of AML in Fanconi anaemia and dyskeratosis congenita.
C1 [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Zeidler, Cornelia; Welte, Karl] Hannover Med Sch, Kinderklin, D-30623 Hannover, Germany.
[Bolyard, Audrey A.; Dale, David C.] Univ Washington, Dept Med, Seattle, WA USA.
[Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD 20852 USA.
[Bonilla, Mary A.] St Josephs Childrens Hosp, Paterson, NJ USA.
[Boxer, Laurence A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Dror, Yigal] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Kinsey, Sally] St James Univ Hosp, Leeds, W Yorkshire, England.
[Link, Daniel C.] Washington Univ, Div Bone Marrow Transplantat, Sch Med, St Louis, MO USA.
[Newburger, Peter E.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8020, Rockville, MD 20852 USA.
EM rosenbep@mail.nih.gov
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics; NIH [2R24AI049393]; German Ministry for Education and
Research, BMBF [01 GM0618]
FX We thank the patients and doctors for participating in the registry, and
the data collection centres in Seattle, WA, and Hannover, Germany, for
maintaining the registry. This research was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Division of Cancer Epidemiology and Genetics; NIH Grant 2R24AI049393; a
gift from the Amgen Foundation; and a grant for the Rare Diseases
Program 'German Network on Congenital Bone Marrow Failure Syndromes' by
the German Ministry for Education and Research, BMBF Grant 01 GM0618.
NR 10
TC 69
Z9 72
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2010
VL 150
IS 2
BP 196
EP 199
DI 10.1111/j.1365-2141.2010.08216.x
PG 4
WC Hematology
SC Hematology
GA 619OD
UT WOS:000279438600008
PM 20456363
ER
PT J
AU Nouraie, M
Reading, NS
Campbell, A
Minniti, CP
Rana, SR
Luchtman-Jones, L
Kato, GJ
Gladwin, MT
Castro, OL
Prchal, JT
Gordeuk, VR
AF Nouraie, Mehdi
Reading, Noel S.
Campbell, Andrew
Minniti, Caterina P.
Rana, Sohail R.
Luchtman-Jones, Lori
Kato, Gregory J.
Gladwin, Mark T.
Castro, Oswaldo L.
Prchal, Josef T.
Gordeuk, Victor R.
TI Association of G6PD202A,376G with lower haemoglobin concentration but
not increased haemolysis in patients with sickle cell anaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE sickle cell anaemia; G6PD; haemolysis; alpha-thalassaemia; haemoglobin
concentration
ID ALPHA-THALASSEMIA; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; G6PD
DEFICIENCY; MALARIA SUSCEPTIBILITY; FETAL-HEMOGLOBIN; DISEASE;
POPULATION; SEVERITY; JAMAICA; CONGO
AB P>The genetic bases of the highly variable degrees of anaemia and haemolysis in persons with Hb SS are not fully known, but several studies have indicated that G6PD deficiency is not a factor. The G6PD202A and G6PD376G alleles and alpha-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD202A,376G (G6PD A-) was defined as hemizygosity for both alleles in males and homozygosity in females. Among the participants 41% were receiving hydroxycarbamide. The prevalence of G6PD202A,376G was 13 center dot 6% in males and 3 center dot 3% in females with an overall prevalence of 8 center dot 7%. G6PD202A,376G was associated with a 10 g/l decrease in haemoglobin concentration (P = 0 center dot 008) but not with increased haemolysis as measured by lactate dehydrogenase, bilirubin, aspartate-aminotransferase, reticulocyte count or a haemolytic component derived from these markers (P > 0 center dot 09). Similar results were found within a sub-group of children who were not receiving hydroxycarbamide. By comparison, single and double alpha-globin deletions were associated with progressively higher haemoglobin concentrations (P = 0 center dot 005 for trend), progressively lower values for haemolytic component (P = 0 center dot 007), and increased severe pain episodes (P < 0 center dot 001). In conclusion, G6PD202A,376G may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.
C1 [Nouraie, Mehdi; Rana, Sohail R.; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA.
[Reading, Noel S.] ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA.
[Campbell, Andrew] Univ Michigan, Med Ctr, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
[Minniti, Caterina P.; Kato, Gregory J.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA.
[Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Prchal, Josef T.] Univ Utah, Salt Lake City, UT USA.
RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM vgordeuk@howard.edu
RI Kato, Gregory/I-7615-2014; Reading, Noel/J-8911-2016
OI Kato, Gregory/0000-0003-4465-3217; Reading, Noel/0000-0003-0806-5661
FU NHLBI [2 R25 HL003679-08, 1 R01 HL079912-02]; NCRR, NIH, Bethesda, MD
[2MOI RR10284-10]; National Institutes of Health
FX Supported in part by grant nos. 2 R25 HL003679-08 and 1 R01 HL079912-02
from NHLBI, by Howard University GCRC grant no 2MOI RR10284-10 from
NCRR, NIH, Bethesda, MD, and by the intramural research program of the
National Institutes of Health.
NR 37
TC 11
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2010
VL 150
IS 2
BP 218
EP 225
DI 10.1111/j.1365-2141.2010.08215.x
PG 8
WC Hematology
SC Hematology
GA 619OD
UT WOS:000279438600011
PM 20507315
ER
PT J
AU Galor, A
Feuer, W
Kempen, JH
Kacmaz, RO
Liesegang, TL
Suhler, EB
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Thorne, JE
AF Galor, Anat
Feuer, William
Kempen, John H.
Kacmaz, R. Oktay
Liesegang, Teresa L.
Suhler, Eric B.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Thorne, Jennifer E.
TI Adverse effects of smoking on patients with ocular inflammation
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CIGARETTE-SMOKING; RISK-FACTORS; EYE DISEASE; THERAPY; UVEITIS;
EPIDEMIOLOGY; EPISCLERITIS; PREVALENCE; PREDICTORS; SCLERITIS
AB Background To evaluate how smoking affects the time to disease quiescence and time to disease recurrence in patients with ocular inflammation.
Methods A retrospective cohort study of patients with ocular inflammation who were followed longitudinally and had smoking information available in the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study database.
Results Among 2676 patients with active ocular inflammation, smokers were more likely to have bilateral ocular disease and poorer visual acuity on presentation compared with non-smokers and previous smokers. In a multivariate analysis, there was no statistically significant difference in the time to disease quiescence between groups. However, the median time to recurrence of ocular inflammation was statistically significantly longer for non-smokers (9.4 months) and for previous smokers (10.7 months) than for current smokers (7.8 months) (p=0.02). The RR of ocular inflammation recurrence was higher for smokers than for non-smokers (adjusted HR 1.19, 95% CI 1.03 to 1.37) and tended towards significance in previous smokers (adjusted HR 1.11, 95% CI 0.93 to 1.35).
Conclusions Smoking was associated with an increased likelihood of bilateral ocular inflammation and reduced vision upon presentation, and an increased risk of recurrence compared with not smoking. These results suggest that patients with ocular inflammation should be counselled to stop smoking as part of routine management.
C1 [Galor, Anat; Feuer, William] Univ Miami, Bascom Palmer Eye Inst, Coral Gables, FL 33124 USA.
[Galor, Anat] Univ Penn, Dept Ophthalmol, Miami Vet Adm Med Ctr, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Dept Ophthalmol, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Liesegang, Teresa L.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
RP Thorne, JE (reprint author), Wilmer Eye Inst, 550 N Broadway,Suite 700, Baltimore, MD 21287 USA.
EM jthorne@jhmi.edu
FU National Eye Institute [EY014943]; Bascom Palmer Eye Institute [P30
EY014801]; Research to Prevent Blindness; Paul and Evanina Mackall
Foundation; US Department of Veterans' Affairs; National Eye Institute
FX This study was supported primarily by National Eye Institute Grant
EY014943 (to JHK). Data analysis was supported by core center grant P30
EY014801 (Bascom Palmer Eye Institute), from the National Eye Institute,
unrestricted funds from Research to Prevent Blindness, and the Paul and
Evanina Mackall Foundation. JHK is a Research to Prevent Blindness James
S. Adams Special Scholar Award recipient. DAJ and JTR are Research to
Prevent Blindness Senior Scientific Investigator Award recipients. JET
is a Research to Prevent Blindness Harrington Special Scholar Award
recipient. GAL-C was previously supported by, and RBN continues to be
supported by, intramural funds of the National Eye Institute. AG and EBS
receive support from the US Department of Veterans' Affairs.
NR 23
TC 17
Z9 17
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2010
VL 94
IS 7
BP 848
EP 853
DI 10.1136/bjo.2009.174466
PG 6
WC Ophthalmology
SC Ophthalmology
GA 621GR
UT WOS:000279564400008
PM 20606023
ER
PT J
AU Karev, GP
AF Karev, G. P.
TI Replicator Equations and the Principle of Minimal Production of
Information
SO BULLETIN OF MATHEMATICAL BIOLOGY
LA English
DT Article
DE Production of information; KL-divergence; Replicator equation; Global
demography; Quasispecies equation
ID CROSS-ENTROPY MINIMIZATION; STATISTICAL-MECHANICS; NATURAL-SELECTION;
POPULATIONS; DYNAMICS; PATTERNS; MODELS
AB Many complex systems in mathematical biology and other areas can be described by the replicator equation. We show that solutions of a wide class of replicator equations minimize the KL-divergence of the initial and current distributions under time-dependent constraints, which in their turn, can be computed explicitly at every instant due to the system dynamics. Therefore, the Kullback principle of minimum discrimination information, as well as the maximum entropy principle, for systems governed by the replicator equations can be derived from the system dynamics rather than postulated. Applications to the Malthusian inhomogeneous models, global demography, and the Eigen quasispecies equation are given.
C1 NIH, Lockheed Martin MSD, Bethesda, MD 20894 USA.
RP Karev, GP (reprint author), NIH, Lockheed Martin MSD, Bldg 38A,Rm 5N511N,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM karev@ncbi.nlm.nih.gov
NR 37
TC 10
Z9 10
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0092-8240
J9 B MATH BIOL
JI Bull. Math. Biol.
PD JUL
PY 2010
VL 72
IS 5
BP 1124
EP 1142
DI 10.1007/s11538-009-9484-9
PG 19
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 627TL
UT WOS:000280065700004
PM 20146021
ER
PT J
AU Cook, KM
Figg, WD
AF Cook, Kristina M.
Figg, William D.
TI Angiogenesis Inhibitors: Current Strategies and Future Prospects
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Article
ID ENDOTHELIAL-GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; CELL LUNG-CANCER;
TYROSINE KINASE INHIBITORS; PHASE-III TRIAL; FARNESYL-PROTEIN
TRANSFERASE; METASTATIC COLORECTAL-CANCER; VASCULAR-PERMEABILITY FACTOR;
SUPPRESSES TUMOR-GROWTH; FACTOR EXPRESSION
AB Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth. An extensive array of compounds is currently in preclinical development, with many now entering the clinic and/or achieving approval from the US Food and Drug Administration. Several regulatory and signaling molecules governing angiogenesis are of interest, including growth factors (eg, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor), receptor tyrosine kinases, and transcription factors such as hypoxia inducible factor, as well as molecules involved in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling. Pharmacologic agents have been identified that target these pathways, yet for some agents (notably thalidomide), an understanding of the specific mechanisms of antitumor action has proved elusive. The following review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy. CA Cancer J Clin 2010;60:222-243. (C) 2010 American Cancer Society, Inc.
C1 [Cook, Kristina M.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch & Affiliates, NIH, Bethesda, MD 20892 USA.
[Cook, Kristina M.] Univ New S Wales, Adult Canc Program, Lowy Canc Res Ctr, Sydney, NSW, Australia.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch & Affiliates, NIH, 10 Ctr Dr,9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016;
OI Cook, Kristina/0000-0002-0503-7166
FU Intramural NIH HHS [Z01 SC006538-14]
NR 205
TC 212
Z9 228
U1 5
U2 40
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-9235
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD JUL-AUG
PY 2010
VL 60
IS 4
BP 222
EP 243
DI 10.3322/caac.20075
PG 22
WC Oncology
SC Oncology
GA 625CU
UT WOS:000279870900004
PM 20554717
ER
PT J
AU Annunziata, CM
Stavnes, HT
Kleinberg, L
Berner, A
Hernandez, LF
Birrer, MJ
Steinberg, SM
Davidson, B
Kohn, EC
AF Annunziata, Christina M.
Stavnes, Helene Tuft
Kleinberg, Lilach
Berner, Aasmund
Hernandez, Lidia F.
Birrer, Michael J.
Steinberg, Seth M.
Davidson, Ben
Kohn, Elise C.
TI Nuclear Factor kappa B Transcription Factors Are Coexpressed and Convey
a Poor Outcome in Ovarian Cancer
SO CANCER
LA English
DT Article
DE nuclear factor kappa B; ovarian cancer; immunohistochemistry; survival;
p50; matrix metalloproteinase 9; prognosis
ID DOSE-INTENSE PACLITAXEL; PROMOTES TUMOR-GROWTH; INITIAL THERAPY;
CARCINOMA; CYCLOPHOSPHAMIDE; ANGIOGENESIS; PROGRESSION; METASTASIS;
TRANSITION; EXPRESSION
AB BACKGROUND: Recent work has suggested a role for nuclear factor kappa B (NF-kappa B) in the propagation of ovarian cancer cell lines, but the significance and mechanism of NF-kappa B in ovarian cancer is unknown. The authors hypothesized that the NF-kappa B pathway is over activated in aggressive ovarian cancers. METHODS: The levels of 3 NF-kappa B transcription factors, the activating inhibitors of NF-kappa B (I kappa B) kinases, and the NF-kappa B target matrix metalloproteinase 9 (MMP9) were assessed by immunohistochemistry in specimens of ovarian cancer that were obtained at diagnosis from a cohort of 33 patients who subsequently received combined paclitaxel, cisplatin, and cyclophosphamide. Associations were made between NF-kappa B pathway proteins and outcome. The validation of coexpression was performed at the gene level in 2 independently collected cohorts of 185 and 153 ovarian cancers. RESULTS: The presence of NF-kappa B proteins in newly diagnosed advanced ovarian cancers was established, and a potential association with overall survival was identified. Transcription factors p65 and v-rel reticuloendotheliosis viral oncogene homolog B (RelB) were coexpressed with I kappa B kinase alpha, 1 component of a key trimolecular regulatory complex. Coexpression of the NF-kappa B machinery suggested activity of NF-kappa B signaling in these ovarian tumors. A significant association of p50 with poor overall survival was observed (P = .02). MMP9 expression had the opposite association, in which patients who had tumors without MMP9 staining had the poorest prognosis (P = .01), and this association held true at the gene expression level in an independently collected cohort of 185 ovarian cancers. CONCLUSIONS: The deregulation of NF-kappa B activity may influence outcome in women who receive standard therapy for advanced ovarian cancer. Modification of the NF-kappa B pathway may present an opportunity to improve outcome in the subset of women who have pathway activity. Cancer 2010;116:3276-84. (C) 2070 American Cancer Society.
C1 [Annunziata, Christina M.; Hernandez, Lidia F.; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stavnes, Helene Tuft; Kleinberg, Lilach; Berner, Aasmund; Davidson, Ben] Rikshosp Univ Hosp, Div Pathol, Norwegian Radium Hosp, Oslo, Norway.
[Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Davidson, Ben] Univ Oslo, Fac Div, Radiumhosp Med Fac, Oslo, Norway.
RP Annunziata, CM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM annunzic@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU Center for Cancer Research, NCI; Marsha Rivkin Foundation for Ovarian
Cancer Research; Norwegian Cancer Society; Health Region of
South-Eastern Norway
FX Supported by the Intramural Program of the Center for Cancer Research,
NCI (Drs. Annunziata and Kohn), the Marsha Rivkin Foundation for Ovarian
Cancer Research (Dr. Annunziata), and by grants from the Norwegian
Cancer Society and the Health Region of South-Eastern Norway (Dr.
Davidson).
NR 28
TC 70
Z9 75
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 1
PY 2010
VL 116
IS 13
BP 3276
EP 3284
DI 10.1002/cncr.25190
PG 9
WC Oncology
SC Oncology
GA 616KS
UT WOS:000279208900028
PM 20564628
ER
PT J
AU Gao, R
Price, DK
Dahut, WL
Reed, E
Figg, WD
AF Gao, Rui
Price, Douglas K.
Dahut, William L.
Reed, Eddie
Figg, William D.
TI Genetic polymorphisms in XRCC1 associated with radiation therapy in
prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE DNA excision repair; BER; XRCC1; prostate cancer; radiotherapy; genetic
polymorphism; haplotype
ID SINGLE NUCLEOTIDE POLYMORPHISMS; DNA-REPAIR GENES; POLY(ADP-RIBOSE)
POLYMERASE; LUNG-CANCER; CELL-LINES; RADIOTHERAPY; RISK; DAMAGE;
RADIOSENSITIVITY; HAPLOTYPES
AB Radiation therapy is a potentially curative, important treatment option in localized prostate cancer. However, at 8 years after radiation therapy, even in the best risk subset of patients, approximately 10% of patients will experience clinical disease recurrence. The identification of molecular markers of treatment success or failure may allow for the development of strategies to further improve treatment outcomes. Herein, we investigated five molecular markers of DNA repair. 513 patients with castrate-resistant prostate cancer (CRPC), including 284 patients who received radiotherapy, 229 patients without radiotherapy and 152 healthy individuals were genotyped for five polymorphisms in DNA excision repair genes: ERCC1 N118N (500C>T), XPD K751Q (2282A>C), XRCC1 R194W (685C>T), XRCC1 R399Q (1301G>A) and PARP1 V762A (2446T>C). The distribution of genetic polymorphisms in the patients with CRPC and in healthy controls was compared, and the association between the polymorphisms and overall survival was investigated. The polymorphisms evaluated did not show differences between the patient group and the healthy controls, nor did they show a trend toward an association with survival. However, in the radiation treated subgroup, the median survival time was associated with the XRCC1 haplotype. The median survival time was 11.75 years for patients with the R399Q AA/R194W CC haplotype, 12.17 years for patients with the R399Q AG/R194W CC haplotype, 6.665 years for patients with the R399Q AG/R194W CT haplotype, and 6.21 years for patients with the R399Q GG/R194W CT haplotype (p = 0.034). This association was not found when all patients were investigated. We conclude that the genetic polymorphisms in XRCC1 may affect the outcome in patients who received radiotherapy for localized prostate cancer.
C1 [Gao, Rui; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
[Gao, Rui; Price, Douglas K.; Dahut, William L.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gao, Rui] Univ Maryland, College Pk, MD 20742 USA.
[Reed, Eddie] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 33
TC 19
Z9 19
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUL 1
PY 2010
VL 10
IS 1
BP 13
EP 18
DI 10.4161/cbt.10.1.12172
PG 6
WC Oncology
SC Oncology
GA 621PS
UT WOS:000279593900003
PM 20495366
ER
PT J
AU Cardenas-Navia, LI
Cruz, P
Lin, JC
Rosenberg, SA
Samuels, Y
AF Cardenas-Navia, L. Isabel
Cruz, Pedro
Lin, Jimmy C.
Rosenberg, Steven A.
Samuels, Yardena
CA NISC Comparative Sequencing
TI Novel somatic mutations in heterotrimeric G proteins in melanoma
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE heterotrimeric G proteins; GNG10; GNAZ; melanoma
ID COUPLED RECEPTORS; CANCER INVASION; ALPHA-SUBUNIT; G12 FAMILY;
POLYMORPHISM; METASTASIS; BETA-3-SUBUNIT; ACTIVATION; EXPRESSION;
REVEALS
AB Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate signals between G-protein coupled receptors and their downstream pathways, and have been shown to be mutated in cancer. In particular, GNAQ was found to be frequently mutated in blue nevi of the skin and uveal melanoma, acting as an oncogene in its mutated form. To further examine the role of heterotrimeric G proteins in melanoma, we performed a comprehensive mutational analysis of the 35 genes in the heterotrimeric G protein gene family in a panel of 80 melanoma samples. Somatic alterations in a G protein subunit were detected in 17% of samples spanning seven genes. The highest rates of somatic, non-synonymous mutations were found in GNG10 and GNAZ, neither of which has been previously reported to be mutated in melanoma. Our study is the first systematic analysis of the heterotrimeric G proteins in melanoma and indicates that multiple mutated heterotrimeric G proteins may be involved in melanoma progression.
C1 [Cardenas-Navia, L. Isabel; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Cruz, Pedro] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU National Human Genome Research Institute; National Cancer Institute,
National Institutes of Health
FX We thank members of the NISC Comparative Sequencing Program for
providing leadership in the generation of the sequence data analyzed
here. Funded by the National Human Genome Research Institute and
National Cancer Institute, National Institutes of Health.
NR 30
TC 8
Z9 9
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUL 1
PY 2010
VL 10
IS 1
BP 33
EP 37
DI 10.4161/cbt.10.1.11949
PG 5
WC Oncology
SC Oncology
GA 621PS
UT WOS:000279593900006
PM 20424519
ER
PT J
AU Sun, HH
Pisle, S
Gardner, ER
Figg, WD
AF Sun, Haihao
Pisle, Stephen
Gardner, Erin R.
Figg, William D.
TI Bioluminescent imaging study FAK inhibitor, PF-562,271, preclinical
study in PC3M-luc-C6 local implant and metastasis xenograft models
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE prostate cancer; in vivo; luciferase; focal adhesion kinase
ID FOCAL-ADHESION KINASE; PROSTATE-CANCER; IN-VIVO; BONE METASTASES;
PATHOGENESIS; EXPRESSION; PHENOTYPE
AB Focal adhesion kinase (FAK) is essential in regulating integrin signaling pathways responsible for cell survival and proliferation, as well as motility, making FAK a distinctive target in the field of anticancer drug development, especially with regards to metastatic disease.(1) Our objective was to demonstrate tumor growth inhibition by PF-562,271, a selective inhibitor of FAK and FAK2, or Pyk2,(2) in mouse xenograft models, both subcutaneous and metastatic, employing the human prostate cancer cell line PC3M-luc-C6, a modified PC3M cell line that expresses luciferase. After 2 weeks of treatment with PF-562,271, 25 mg/kg PO BID 5x/wk, the subcutaneous model showed a 62% tumor growth inhibition compared to control based on tumor measurements (p < 0.05), with a 88 vs. a 490% increase in bioluminescent signal for treatment and control respectively (p < 0.05). In the metastasis model, the percent change from baseline, after 18 days of treatment, of the treatment group was 2,854 vs. 14,190% for the vehicle (p < 0.01). These results show that PF-562,271 has a potent effect on metastatic prostate cancer growth in vivo.
C1 [Sun, Haihao; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
[Pisle, Stephen; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gardner, Erin R.] NCI Frederick, SAIC Frederick, Clin Pharmacol Program, Frederick, MD USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds From
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E (E.R.G.). This work was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 15
TC 19
Z9 21
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUL 1
PY 2010
VL 10
IS 1
BP 38
EP 43
DI 10.4161/cbt.10.1.11993
PG 6
WC Oncology
SC Oncology
GA 621PS
UT WOS:000279593900007
PM 20495381
ER
PT J
AU Gibson, TM
Weinstein, SJ
Mayne, ST
Pfeiffer, RM
Selhub, J
Taylor, PR
Virtamo, J
Albanes, D
Stolzenberg-Solomon, R
AF Gibson, Todd M.
Weinstein, Stephanie J.
Mayne, Susan T.
Pfeiffer, Ruth M.
Selhub, Jacob
Taylor, Philip R.
Virtamo, Jarmo
Albanes, Demetrius
Stolzenberg-Solomon, Rachael
TI A prospective study of one-carbon metabolism biomarkers and risk of
renal cell carcinoma
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Folate; Renal cell carcinoma; Biological markers; Nested case-control
study; B vitamins
ID CANCER-RISK; UNITED-STATES; FOLATE INTAKE; PANCREATIC-CANCER;
CIGARETTE-SMOKING; BLOOD FOLATE; VEGETABLES; PLASMA; HOMOCYSTEINE;
FRUITS
AB Previous studies have found associations between one-carbon metabolism factors and risk of several cancers, but little is known regarding renal cell carcinoma (RCC). We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a prospective study of Finnish male smokers aged 50-69 at baseline.
Prediagnostic folate, vitamin B(6), vitamin B(12), cysteine, riboflavin, and homocysteine concentrations were measured in fasting serum from 224 incident RCC cases and 224 controls (matched on age and date of serum collection). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders.
Serum folate tended to be inversely associated with RCC, compared to the first quartile, the odds ratios (95% CI) for subsequent quartiles were 0.62 (0.35-1.08), 0.52 (0.29-0.93), and 0.67 (0.37-1.20) (P-trend = 0.19). When modeled as a threshold effect, subjects in the lowest serum folate quartile (a parts per thousand currency sign6.64 nmol/l), which corresponds to deficient folate status, had a significant increased RCC risk (OR = 1.68, 95% CI 1.06-2.65) compared to those with higher serum folate. The other one-carbon metabolism biomarkers were not associated with RCC.
This study in male smokers suggests that deficient folate status may increase risk of RCC, but confirmation is needed in other epidemiologic studies that include women and non-smokers.
C1 [Gibson, Todd M.; Weinstein, Stephanie J.; Pfeiffer, Ruth M.; Taylor, Philip R.; Albanes, Demetrius; Stolzenberg-Solomon, Rachael] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Gibson, Todd M.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
[Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
RP Gibson, TM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM gibsontm@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015
FU NIH, National Cancer Institute [TU2-CA-105666]; National Cancer
Institute, Department of Health and Human Services [N01-CN-45165,
N01-RC-45035, N01-RC-37004]
FX This research was supported in part by the Intramural Research Program
of the NIH and the National Cancer Institute and by grant TU2-CA-105666.
Additionally, this research was supported by Public Health Service
contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National
Cancer Institute, Department of Health and Human Services.
NR 46
TC 15
Z9 16
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2010
VL 21
IS 7
BP 1061
EP 1069
DI 10.1007/s10552-010-9534-5
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 608WE
UT WOS:000278615900009
PM 20383577
ER
PT J
AU Chang, CM
Schroeder, JC
Olshan, AF
Dunphy, CH
Huang, WY
Baric, RS
Conway, K
Cerhan, JR
Lynch, CF
Rothman, N
Cantor, KP
Blair, A
AF Chang, Cindy M.
Schroeder, Jane C.
Olshan, Andrew F.
Dunphy, Cherie H.
Huang, Wen-Yi
Baric, Ralph S.
Conway, Kathleen
Cerhan, James R.
Lynch, Charles F.
Rothman, Nathaniel
Cantor, Kenneth P.
Blair, Aaron
TI A case-control study of tobacco use and other non-occupational risk
factors for lymphoma subtypes defined by t(14;18) translocations and
bcl-2 expression
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Bcl-2; Epidemiology; Lymphoma; Molecular genes; Non-Hodgkin; Tobacco;
Translocation (genetics); FISH; t(14;18)
ID NON-HODGKINS-LYMPHOMA; IN-SITU HYBRIDIZATION; EPIDEMIOLOGY CONSORTIUM
INTERLYMPH; POLYMERASE-CHAIN-REACTION; CIGARETTE-SMOKING; FOLLICULAR
LYMPHOMA; POOLED ANALYSIS; UNITED-STATES; PERIPHERAL-BLOOD; DIAGNOSIS
AB We re-evaluated reported associations between tobacco use and other factors and non-Hodgkin lymphoma (NHL) t(14; 18)-subtypes based on fluorescence in situ hybridization (FISH) assays believed to be more sensitive than polymerase chain reaction (PCR), previously used for detecting t(14; 18).
Commercial FISH assays and bcl-2 immunostaining were performed on paraffin sections to determine t(14; 18) and bcl-2 case-subtypes. Polytomous logistic regression models estimated associations between NHL case-subtypes (versus 1,245 population-based controls) and tobacco use as well as other factors.
Adjusting for age, state, and proxy status, t(14; 18)-negative NHL was associated with any tobacco use (vs. no tobacco use, OR = 1.9, 95% CI = 1.0-3.5), including current smoking (vs. no cigarette use, OR = 1.9, 95% CI = 1.1-3.2). Tobacco exposures were not clearly associated with t(14; 18)-positive NHL or bcl-2 case-subtypes. Hair-dye use and family history of a hemolymphatic cancer were associated with t(14; 18)-negative NHL, but the number of exposed cases was small.
The association between t(14; 18)-negative NHL and cigarette smoking was unexpected given previous evidence of associations between smoking and follicular lymphoma (which is largely t(14; 18)-positive). Future studies characterizing additional molecular characteristics of t(14; 18)-negative NHL may help determine whether the association with smoking may have been causal versus an artifact of chance or bias.
C1 [Chang, Cindy M.] NCI, Infect & Immunoepidemiol Branch, Rockville, MD USA.
[Schroeder, Jane C.; Olshan, Andrew F.; Baric, Ralph S.; Conway, Kathleen] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Dunphy, Cherie H.] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Huang, Wen-Yi; Rothman, Nathaniel; Cantor, Kenneth P.; Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Cerhan, James R.] Mayo Clin, Rochester, MN USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
RP Chang, CM (reprint author), NCI, Infect & Immunoepidemiol Branch, Rockville, MD USA.
EM changcm@mail.nih.gov
RI Chang, Cindy/G-4514-2010;
OI Cerhan, James/0000-0002-7482-178X
FU UNC Lineberger Comprehensive Cancer Center; National Institutes of
Health [P30ES10126]; National Cancer Institute [R03 CA71617-01]
FX This study was supported in part by the UNC Lineberger Comprehensive
Cancer Center (Population Sciences Research Award), the Intramural
Program of the National Institutes of Health (Environmental Health
Sciences (P30ES10126)) and the National Cancer Institute (R03
CA71617-01). Special thanks to Sophia Wang and Charles Rabkin from the
National Cancer Institute, David W. Cowan, Stephen Oglesbee, Georgette
Dent, and Boyd Yount from UNC-Chapel Hill, Clarice Weinberg from the
National Institute of Environmental Health Sciences, and Paige Tolbert
from Emory University.
NR 41
TC 8
Z9 8
U1 1
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2010
VL 21
IS 7
BP 1147
EP 1154
DI 10.1007/s10552-010-9531-8
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 608WE
UT WOS:000278615900017
PM 20232134
ER
PT J
AU Gage, JC
Schiffman, M
Solomon, D
Wheeler, CM
Castle, PE
AF Gage, Julia C.
Schiffman, Mark
Solomon, Diane
Wheeler, Cosette M.
Castle, Philip E.
TI Comparison of Measurements of Human Papillomavirus Persistence for
Postcolposcopic Surveillance for Cervical Precancerous Lesions
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; UNDETERMINED SIGNIFICANCE;
INTRAEPITHELIAL NEOPLASIA; CYTOLOGY INTERPRETATIONS; RANDOMIZED-TRIAL;
BETHESDA SYSTEM; CANCER; WOMEN; RISK
AB Objective: Following guidelines, women evaluated by colposcopy, but not found to have a precancerous lesion, could be tested again at 12 months for carcinogenic human papillomavirus (HPV). Compared with pooled-probe testing, measuring HPV genotype-specific persistence might better predict subsequent grade 3 cervical intraepithelial neoplasia (CIN3).
Methods: For women enrolled in the immediate colposcopy arm of the Atypical squamous cells of undetermined significance (ASCUS) and Low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS), who underwent enrollment colposcopy but were without prevalently detected CIN2 or worse (CIN2+; n = 671), we compared 1-year HPV persistence, as measured by a pooled HPV genotype test (hybrid capture 2; hc2) versus a research PCR HPV genotyping test (line blot assay; LBA) as predictors of "missed prevalent" or possibly incident CIN3 diagnosed between 12 and 24 months.
Results: Thirty-two (4.8%) women were diagnosed with subsequent CIN3. Testing repeatedly hc2-positive (hc2+) was more common (49.0%) than genotype-specific persistence as detected by LBA (30.3%, P < 0.01). Although absolute risks of CIN3 following repeat hc2+ or genotype-specific persistence were similar (8.8% versus 8.4%, P = 0.86), repeat hc2+ was more sensitive for identifying CIN3 than genotype-specific persistence (90.6% versus 53.1%, P < 0.01). Among 329 women repeatedly hc2+, women with persistent HPV16 were at higher risk of CIN3 than non-HPV16-persistent women (23.1% versus 7.0%, P < 0.01).
Conclusions: For postcolposcopy management, 1-year HPV persistence as measured by hc2 would recall more women but was more sensitive and similarly predictive for CIN3 in the following year than detection of genotype-specific persistence by LBA.
Impact: Although find little utility for measuring type-specific persistence, testing for persistent HPV16 might be clinically useful. Cancer Epidemiol Biomarkers Prev; 19(7); 1668-74. (C) 2010 AACR.
C1 [Gage, Julia C.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Gage, Julia C.; Schiffman, Mark; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Sch Med, Albuquerque, NM 87131 USA.
[Wheeler, Cosette M.] Univ New Mexico, Dept Obstet & Gynecol, Hlth Sci Ctr, Sch Med, Albuquerque, NM 87131 USA.
RP Gage, JC (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7013, Rockville, MD 20852 USA.
EM gagej@mail.nih.gov
FU National Cancer Institute, NIH, Department of Health and Human Services
[CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159,
CN-55105]
FX Intramural program of the National Cancer Institute, NIH, Department of
Health and Human Services, and contracts CN-55153, CN-55154, CN-55155,
CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105.
NR 26
TC 11
Z9 12
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1668
EP 1674
DI 10.1158/1055-9965.EPI-09-1286
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100001
PM 20615884
ER
PT J
AU Castle, PE
Schiffman, M
Wheeler, CM
Wentzensen, N
Gravitt, PE
AF Castle, Philip E.
Schiffman, Mark
Wheeler, Cosette M.
Wentzensen, Nicolas
Gravitt, Patti E.
TI Human Papillomavirus Genotypes in Cervical Intraepithelial Neoplasia
Grade 3
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; CARCINOGENIC
HUMAN-PAPILLOMAVIRUS; MILDLY ABNORMAL-CYTOLOGY; DNA-POSITIVE WOMEN;
UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; LESION CYTOLOGY;
LINEAR-ARRAY; RISK
AB Background: There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer.
Methods: The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the 2-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results on cervical specimens. The genotyping results were ranked hierarchically according to cancer risk: HPV16 > other carcinogenic HPV > noncarcinogenic HPV > PCR negative.
Results: Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the five most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multiparity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively; P = 0.0003, Kruskal-Wallis).
Conclusions: HPV16-positive CIN3 was more commonly diagnosed in younger women (versus older women), with consensus diagnosis (versus some disagreement between reviewers), and in smokers (versus nonsmokers), and was less commonly diagnosed in multiparous women compared CIN3 positive for other carcinogenic HPV genotypes.
Impact: In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASCUS and LSIL cytology should shift to older ages, possibly permitting later age at first screening. Cancer Epidemiol Biomarkers Prev; 19(7); 1675-81. (C) 2010 AACR.
C1 [Castle, Philip E.; Schiffman, Mark; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
FU National Cancer Institute, NIH Department of Health and Human Services
[CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159,
CN-55105]; NIH, National Cancer Institute
FX The ALTS was supported by the National Cancer Institute, NIH Department
of Health and Human Services contracts CN-55153, CN-55154, CN-55155,
CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105. Some of the
equipment and supplies used in these studies were donated or provided at
reduced cost by Digene Corporation, Gaithersburg, MD; Cytyc Corporation,
Marlborough, MA; National Testing Laboratories, Fenton, MO; DenVu,
Tucson, AZ; TriPath Imaging, Inc., Burlington, NC; and Roche Molecular
Systems Inc., Alameda, CA. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute.
NR 31
TC 34
Z9 36
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1675
EP 1681
DI 10.1158/1055-9965.EPI-10-0251
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100002
PM 20615885
ER
PT J
AU Dubrow, R
Darefsky, AS
Park, Y
Mayne, ST
Moore, SC
Kilfoy, B
Cross, AJ
Sinha, R
Hollenbeck, AR
Schatzkin, A
Ward, MH
AF Dubrow, Robert
Darefsky, Amy S.
Park, Yikyung
Mayne, Susan T.
Moore, Steven C.
Kilfoy, Briseis
Cross, Amanda J.
Sinha, Rashmi
Hollenbeck, Albert R.
Schatzkin, Arthur
Ward, Mary H.
TI Dietary Components Related to N-Nitroso Compound Formation: A
Prospective Study of Adult Glioma
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION;
HISTOLOGY-SPECIFIC ANALYSIS; RETIRED-PERSONS DIET; PRIMARY BRAIN-TUMORS;
DRINKING-WATER; MEAT INTAKE; ENDOGENOUS FORMATION; NATIONAL-INSTITUTES;
CANCER PREVENTION
AB Background: N-nitroso compounds (NOC) are found in processed meat and are formed endogenously from intake of nitrite and nitrate. Endogenous NOC formation is antagonized by nitrosation inhibitors in fruit and vegetables (e. g., vitamin C) and promoted by heme in red meat. It has been hypothesized that a diet resulting in high exposure to NOCs increases adult glioma risk.
Methods: Using proportional hazards models, we tested this hypothesis among 545,770 participants in the prospective NIH-AARP Diet and Health Study, which assessed dietary intake at baseline (1995-1996) with a comprehensive food frequency questionnaire, and at ages 12 to 13 years with an abbreviated food frequency questionnaire.
Results: During follow-up through 2003, 585 participants were diagnosed with glioma. We found no significant trends in glioma risk for consumption of processed or red meat, nitrate, or vitamin C or E. We found significant positive trends for nitrite intake from plant sources (hazard ratio for quintile 5 versus quintile 1, 1.59; 95% confidence interval, 1.20-2.10; P for trend = 0.028) and, unexpectedly, for fruit and vegetable intake (hazard ratio, 1.42; 95% confidence interval, 1.08-1.86; P for trend = 0.0081). Examination of interactions between dietary intakes (e. g., nitrite and vitamin C) and a limited analysis of diet at ages 12 to 13 years provided no support for the NOC hypothesis.
Conclusions: Our results suggest that consumption of processed or red meat, nitrite, or nitrate does not increase adult glioma risk, and that consumption of fruit and vegetables, vitamin C, or vitamin E does not reduce risk.
Impact: Our results, in agreement with the only previous prospective analysis, cast doubt on the NOC hypothesis in relation to dietary intake and adult glioma risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1709-22. (C) 2010 AACR.
C1 [Dubrow, Robert; Darefsky, Amy S.; Mayne, Susan T.] Yale Univ, Yale Sch Publ Hlth, Sch Med, New Haven, CT 06520 USA.
[Park, Yikyung; Moore, Steven C.; Kilfoy, Briseis; Cross, Amanda J.; Sinha, Rashmi; Schatzkin, Arthur; Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Dubrow, R (reprint author), Yale Univ, Yale Sch Publ Hlth, Sch Med, 60 Coll St,POB 208034, New Haven, CT 06520 USA.
EM robert.dubrow@yale.edu
RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Sinha, Rashmi/G-7446-2015;
Moore, Steven/D-8760-2016;
OI Sinha, Rashmi/0000-0002-2466-7462; Moore, Steven/0000-0002-8169-1661;
Park, Yikyung/0000-0002-6281-489X
FU NIH, National Cancer Institute
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute.
NR 55
TC 23
Z9 23
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1709
EP 1722
DI 10.1158/1055-9965.EPI-10-0225
PG 14
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100006
PM 20570910
ER
PT J
AU Galeone, C
Tavani, A
Pelucchi, C
Turati, F
Winn, DM
Levi, F
Yu, GP
Morgenstern, H
Kelsey, K
Dal Maso, L
Purdue, MP
McClean, M
Talamini, R
Hayes, RB
Franceschi, S
Schantz, S
Zhang, ZF
Ferro, G
Chuang, SC
Boffetta, P
La Vecchia, C
Hashibe, M
AF Galeone, Carlotta
Tavani, Alessandra
Pelucchi, Claudio
Turati, Federica
Winn, Deborah M.
Levi, Fabio
Yu, Guo-Pei
Morgenstern, Hal
Kelsey, Karl
Dal Maso, Luigino
Purdue, Mark P.
McClean, Michael
Talamini, Renato
Hayes, Richard B.
Franceschi, Silvia
Schantz, Stimson
Zhang, Zuo-Feng
Ferro, Gilles
Chuang, Shu-Chun
Boffetta, Paolo
La Vecchia, Carlo
Hashibe, Mia
TI Coffee and Tea Intake and Risk of Head and Neck Cancer: Pooled Analysis
in the International Head and Neck Cancer Epidemiology Consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID UPPER-AERODIGESTIVE TRACT; FOOD FREQUENCY QUESTIONNAIRE; ORAL-CANCER;
PHARYNGEAL CANCER; LARYNGEAL-CANCER; OROPHARYNGEAL CANCER; DIETARY
INDICATORS; ALCOHOL; SMOKING; CONSUMPTION
AB Background: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results.
Methods: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders.
Results: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94-0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47-0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30-0.71 for oral cavity; OR, 0.58; 95% CI, 0.41-0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37-1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64-1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89-1.11 for drinkers versus nondrinkers).
Conclusions: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx.
Impact: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance. Cancer Epidemiol Biomarkers Prev; 19(7); 1723-36. (C) 2010 AACR.
C1 [Hashibe, Mia] Univ Utah, Sch Med, Div Publ Hlth, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA.
[Galeone, Carlotta; Tavani, Alessandra; Pelucchi, Claudio; Turati, Federica; La Vecchia, Carlo] Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy.
[Galeone, Carlotta; Turati, Federica; La Vecchia, Carlo] Univ Milan, Dipartimento Med Lavoro Clin Lavoro Luigi Devoto, Sez Stat Med & Biometria Giulio A Maccacaro, Milan, Italy.
[Winn, Deborah M.; Purdue, Mark P.] NCI, Bethesda, MD 20892 USA.
[Levi, Fabio] CHU Vaudois, Inst Univ Med Sociale & Prevent, CH-1011 Lausanne, Switzerland.
[Levi, Fabio] Univ Lausanne, Lausanne, Switzerland.
[Yu, Guo-Pei; Schantz, Stimson] New York Eye & Ear Infirm, New York, NY 10003 USA.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Kelsey, Karl] Brown Univ, Providence, RI 02912 USA.
[Dal Maso, Luigino; Talamini, Renato] Aviano Canc Ctr, I-33081 Aviano, Italy.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Franceschi, Silvia; Ferro, Gilles; Hashibe, Mia] Int Agcy Res Canc, F-69372 Lyon, France.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Chuang, Shu-Chun] Univ London Imperial Coll Sci Technol & Med, London, England.
RP Hashibe, M (reprint author), Univ Utah, Sch Med, Div Publ Hlth, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA.
EM mia.hashibe@utah.edu
RI Chuang, Shu-Chun/N-3358-2013; Purdue, Mark/C-9228-2016; Turati,
Federica/K-3841-2016;
OI Purdue, Mark/0000-0003-1177-3108; Turati, Federica/0000-0002-5841-5773;
dal maso, luigino/0000-0001-6163-200X; La Vecchia,
Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X
FU NIH, National Cancer Institute (NCI) [R03CA113157, CA100679, CA78609];
Italian Association for Research on Cancer; Swiss Cancer League,
Switzerland [KFS1069-09-2000]; Italian League against Cancer; Italian
Ministry of Research; Swiss League against Cancer; Swiss Research
against Cancer/Oncosuisse [KFS-700 and OCS-1633]; NIH [P50CA90388,
R01DA11386, R03CA77954, T32CA09142, U01CA96134, R21ES011667,
R01CA51845]; University of California at Los Angeles Jonsson
Comprehensive Cancer Center; NCI, NIH, United States; NCI; Fondazione
del Monte di Lombardia
FX We thank Dr. Patrizia Lettieri for bibliographic research. C. Galeone
was supported during her permanence at International Agency for Research
on Cancer by "Fondazione del Monte di Lombardia."; This International
Head and Neck Cancer Epidemiology Consortium was supported by NIH,
National Cancer Institute (NCI) grant R03CA113157. The individual
studies were funded by the following grants. Milan study: Italian
Association for Research on Cancer. France study: Swiss Cancer League,
Switzerland (KFS1069-09-2000). Aviano and Italy multicenter studies:
Italian Association for Research on Cancer, Italian League against
Cancer, and Italian Ministry of Research. Swiss study: Swiss League
against Cancer and the Swiss Research against Cancer/Oncosuisse (KFS-700
and OCS-1633). Los Angeles study: NIH (P50CA90388, R01DA11386,
R03CA77954, T32CA09142, U01CA96134, and R21ES011667) and the Alper
Research Program for Environmental Genomics of the University of
California at Los Angeles Jonsson Comprehensive Cancer Center. Boston
study: NIH NCI (CA100679 and CA78609). U.S. multicenter study: The
Intramural Program of the NCI, NIH, United States. Memorial
Sloan-Kettering Cancer Center study: NIH (R01CA51845). Puerto Rico
study: Intramural Research Program of the NIH and the NCI.
NR 62
TC 30
Z9 32
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1723
EP 1736
DI 10.1158/1055-9965.EPI-10-0191
PG 14
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100007
PM 20570908
ER
PT J
AU Chu, LW
Meyer, TE
Li, QZ
Menashe, I
Yu, K
Rosenberg, PS
Huang, WY
Quraishi, SM
Kaaks, R
Weiss, JM
Hayes, RB
Chanock, SJ
Hsing, AW
AF Chu, Lisa W.
Meyer, Tamra E.
Li, Qizhai
Menashe, Idan
Yu, Kai
Rosenberg, Philip S.
Huang, Wen-Yi
Quraishi, Sabah M.
Kaaks, Rudolf
Weiss, Jocelyn M.
Hayes, Richard B.
Chanock, Stephen J.
Hsing, Ann W.
TI Association between Genetic Variants in the 8q24 Cancer Risk Regions and
Circulating Levels of Androgens and Sex Hormone-Binding Globulin
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; COLORECTAL-CANCER; CHROMOSOME
8Q24; SUSCEPTIBILITY LOCUS; MULTIPLE LOCI; IDENTIFICATION; TESTOSTERONE;
SCAN; MEN
AB Background: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.
Methods: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3 alpha diol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels.
Results: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05).
Conclusions: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels.
Impact: These results might provide some clues for the strong link between 8q24 and prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1848-54. (C) 2010 AACR.
C1 [Chu, Lisa W.; Meyer, Tamra E.; Menashe, Idan; Yu, Kai; Rosenberg, Philip S.; Huang, Wen-Yi; Quraishi, Sabah M.; Weiss, Jocelyn M.; Hayes, Richard B.; Chanock, Stephen J.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chu, Lisa W.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
[Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China.
[Kaaks, Rudolf] German Natl Canc Ctr, Div Canc Epidemiol, Heidelberg, Germany.
RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA.
EM HsingA@mail.nih.gov
OI Hayes, Richard/0000-0002-0918-661X
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, Department of Health and
Human Services
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics and contracts from the Division of Cancer Prevention, National
Cancer Institute, NIH, Department of Health and Human Services.
NR 29
TC 10
Z9 10
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1848
EP 1854
DI 10.1158/1055-9965.EPI-10-0101
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100021
PM 20551303
ER
PT J
AU Zhang, LP
Ji, ZY
Guo, WH
Hubbard, AE
Galvan, N
Xin, KX
Azuma, M
Smith, MT
Tang, XJ
Qiu, CY
Ge, YC
Hua, M
Ruan, XL
Li, SH
Xie, YX
Li, LY
Huang, HL
Rothman, N
Shen, M
Freeman, LB
Blair, A
Alter, BP
Moore, LE
Hayes, RB
Hauptmann, M
Stewart, P
Fraumeni, JF
Lan, Q
Vermeulen, R
Reiss, B
Liu, SW
Xiong, J
Kim, S
Rappaport, SM
AF Zhang, Luoping
Ji, Zhiying
Guo, Weihong
Hubbard, Alan E.
Galvan, Noe
Xin, Kerry X.
Azuma, Mariko
Smith, Martyn T.
Tang, Xiaojiang
Qiu, Chuangyi
Ge, Yichen
Hua, Ming
Ruan, Xiaolin
Li, Senhua
Xie, Yuxuan
Li, Laiyu
Huang, Hanlin
Rothman, Nathaniel
Shen, Min
Freeman, Laura Beane
Blair, Aaron
Alter, Blanche P.
Moore, Lee E.
Hayes, Richard B.
Hauptmann, Michael
Stewart, Patricia
Fraumeni, Joseph F., Jr.
Lan, Qing
Vermeulen, Roel
Reiss, Boris
Liu, Songwang
Xiong, Jun
Kim, Sungkyoon
Rappaport, Stephen M.
TI Occupational Exposure to Formaldehyde, Hematotoxicity and
Leukemia-Specific Chromosome Changes in Cultured Myeloid Progenitor
Cells - Response
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
C1 [Zhang, Luoping; Ji, Zhiying; Guo, Weihong; Hubbard, Alan E.; Galvan, Noe; Xin, Kerry X.; Azuma, Mariko; Smith, Martyn T.; Rappaport, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Hua, Ming; Ruan, Xiaolin; Li, Senhua; Xie, Yuxuan; Li, Laiyu; Huang, Hanlin] Guangdong Poisoning Control Ctr, Guangzhou, Guangdong, Peoples R China.
[Rothman, Nathaniel; Shen, Min; Freeman, Laura Beane; Blair, Aaron; Alter, Blanche P.; Moore, Lee E.; Hayes, Richard B.; Hauptmann, Michael; Stewart, Patricia; Fraumeni, Joseph F., Jr.; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Vermeulen, Roel; Reiss, Boris] Univ Utrecht, IRAS, Utrecht, Netherlands.
[Liu, Songwang] Qiaotou Hosp, Dongguan, Guangdong, Peoples R China.
[Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China.
[Kim, Sungkyoon; Rappaport, Stephen M.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
NR 0
TC 3
Z9 3
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2010
VL 19
IS 7
BP 1884
EP 1885
DI 10.1158/1055-9965.EPI-10-0547
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 621OU
UT WOS:000279590100028
ER
PT J
AU Lee, S
Yagita, H
Sayers, TJ
Celis, E
AF Lee, Sujin
Yagita, Hideo
Sayers, Thomas J.
Celis, Esteban
TI Optimized combination therapy using bortezomib, TRAIL and TLR agonists
in established breast tumors
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Breast tumors; Balb-neuT mice; Bortezomib; alpha-DR5; CpG
ID APOPTOSIS-INDUCING LIGAND; PROTEASOME INHIBITOR BORTEZOMIB;
MULTIPLE-MYELOMA; MALIGNANT GLIOMA; RECEPTOR AGONIST; PEPTIDE VACCINE;
T-CELLS; CPG-DNA; CANCER; ANTIBODY
AB TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, which can induce apoptosis in various tumor cells by engaging the receptors, DR4 and DR5. Bortezomib (Velcade) is a proteasome inhibitor that has been approved for patients with multiple myeloma. There is some experimental evidence in preclinical models that bortezomib can enhance the susceptibility of tumors to TRAIL-induced apoptosis. In this study, we investigated the effects of TRAIL-induced death using an agonistic antibody to the TRAIL receptor DR5 (alpha-DR5) in combination with bortezomib administered to mice previously injected with breast cancer cells (TUBO). This combination had some beneficial therapeutic effect, which was significantly enhanced by the co-administration of a Toll-like receptor 9 agonist (CpG). In contrast, single agent treatments had little effect on tumor growth. In addition, we evaluated the effect of combination with alpha-DR5, bortezomib, and CpG in the prevention/treatment of spontaneous mammary tumors in Balb-neuT mice. In this model, which is more difficult to treat, we observed dramatic antitumor effects of alpha-DR5, bortezomib and CpG combination therapy. Since such a mouse model more accurately reflects the immunological tolerance that exists in human cancer, our results strongly suggest that these combination strategies could be directly applied to the therapy for cancer patients.
C1 [Lee, Sujin; Celis, Esteban] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA.
[Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1138421, Japan.
[Sayers, Thomas J.] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc Inflammat Program,Ctr Canc Res, Frederick, MD 21702 USA.
RP Lee, S (reprint author), Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, 2015 Uppergate Dr NE,Room 510, Atlanta, GA 30322 USA.
EM sujin.lee@emory.edu
RI Sayers, Thomas/G-4859-2015
FU National Cancer Institute, National Institutes of Health [R01CA80782,
R01CA103921, NO1-CO-12400, HSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, R01CA80782
and R01CA103921 (E. Celis), under contracts NO1-CO-12400 and
HSN261200800001E (T. Sayers). The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial products
or organizations imply endorsement by the US Government. This Research
was supported (in part) by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 33
TC 10
Z9 11
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD JUL
PY 2010
VL 59
IS 7
BP 1073
EP 1081
DI 10.1007/s00262-010-0834-0
PG 9
WC Oncology; Immunology
SC Oncology; Immunology
GA 589HC
UT WOS:000277136700010
PM 20213120
ER
PT J
AU Morgan, RA
Dudley, ME
Rosenberg, SA
AF Morgan, Richard A.
Dudley, Mark E.
Rosenberg, Steven A.
TI Adoptive Cell Therapy Genetic Modification to Redirect Effector Cell
Specificity
SO CANCER JOURNAL
LA English
DT Review
DE human gene transfer; T-cell receptors (TCRs); chimeric antigen receptors
(CARs); tumor regression
ID TUMOR-INFILTRATING LYMPHOCYTES; CHIMERIC ANTIGEN RECEPTOR; SERIOUS
ADVERSE EVENT; METASTATIC MELANOMA; LENTIVIRAL VECTORS;
ANTITUMOR-ACTIVITY; CANCER REGRESSION; IN-VIVO; ENGINEERED LYMPHOCYTES;
ENHANCED SURVIVAL
AB Building on the principals that the adoptive transfer of T cells can lead to the regression of established tumors in humans, investigators are now further manipulating these cells using genetic engineering. Two decades of human gene transfer experiments have resulted in the translation of laboratory technology into robust clinical applications. The purpose of this review is to give the reader an introduction to the 2 major approaches being developed to redirect effector T-cell specificity. Primary human T cells can be engineered to express exogenous T-cell receptors or chimeric antigen receptors directed against multiple human tumor antigens. Initial clinical trial results have demonstrated that both T-cell receptor-and chimeric antigen receptor-engineered T cells can be administered to cancer patients and mediate tumor regression.
C1 [Morgan, Richard A.; Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
NR 67
TC 60
Z9 63
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2010
VL 16
IS 4
BP 336
EP 341
DI 10.1097/PPO.0b013e3181eb3879
PG 6
WC Oncology
SC Oncology
GA 635QV
UT WOS:000280672100008
PM 20693844
ER
PT J
AU Fewkes, NM
Mackall, CL
AF Fewkes, Natasha M.
Mackall, Crystal L.
TI Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune
Therapies for Cancer
SO CANCER JOURNAL
LA English
DT Review
DE gamma c cytokines; IL-7; IL-15; IL-21; cancer immunotherapy
ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; RECOMBINANT HUMAN INTERLEUKIN-21;
RECEPTOR-BETA CHAIN; IN-VIVO; DENDRITIC CELLS; HOMEOSTATIC
PROLIFERATION; ADOPTIVE IMMUNOTHERAPY; NK CELLS; PHASE-I
AB Cytokines that signal through the common-gamma chain are potent growth factors for T cells and natural killer cells. Interleukin (IL)-2, the gamma c prototype, can mediate antitumor effects as a single agent or in the context of multimodality regimens but is limited by side effects and a propensity for expansion of regulatory T cells. IL-7, IL-15, and IL-21 each possess properties that can be exploited in the context of immunotherapy for cancer. Each has been demonstrated to mediate potent vaccine adjuvant effects in tumor models, and each can enhance the effectiveness of adoptive immunotherapies. Although the overlap among the agents is significant, IL-7 is uniquely immunorestorative and preferentially augments reactivity of naive populations, IL-15 potently augments reactivity of CD8(+) memory cells and natural killer cells, and IL-21 preferentially expands the inflammatory Th17 subset and may limit terminal differentiation of effector CD8(+) cells. Clinical trials of IL-7 and IL-21 have already been completed and, so far, demonstrate safety and biologic activity of these agents. Clinical trials of IL-15 are expected soon. Ultimately, these agents are expected to be most effective in the context of multimodal immunotherapy regimens, and careful clinical trial design will be needed to efficiently identify the proper doses, regimens, and settings in which to exploit their biologic properties for therapeutic gain.
C1 [Fewkes, Natasha M.] Univ Oxford, Dunn Sch Pathol, Oxford OX1 2JD, England.
[Fewkes, Natasha M.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Mackall, CL (reprint author), 0 CRC 1W-3750,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA.
EM mackallc@mail.nih.gov
NR 116
TC 33
Z9 33
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2010
VL 16
IS 4
BP 392
EP 398
DI 10.1097/PPO.0b013e3181eacbc4
PG 7
WC Oncology
SC Oncology
GA 635QV
UT WOS:000280672100016
PM 20693852
ER
PT J
AU Szymanska, K
Moore, LE
Rothman, N
Chow, WH
Waldman, F
Jaeger, E
Waterboer, T
Foretova, L
Navratilova, M
Janout, V
Kollarova, H
Zaridze, D
Matveev, V
Mates, D
Szeszenia-Dabrowska, N
Holcatova, I
Bencko, V
Le Calvez-Kelm, F
Villar, S
Pawlita, M
Boffetta, P
Hainaut, P
Brennan, P
AF Szymanska, K.
Moore, L. E.
Rothman, N.
Chow, W. H.
Waldman, F.
Jaeger, E.
Waterboer, T.
Foretova, L.
Navratilova, M.
Janout, V.
Kollarova, H.
Zaridze, D.
Matveev, V.
Mates, D.
Szeszenia-Dabrowska, N.
Holcatova, I.
Bencko, V.
Le Calvez-Kelm, F.
Villar, S.
Pawlita, M.
Boffetta, P.
Hainaut, P.
Brennan, P.
TI TP53, EGFR, and KRAS mutations in relation to VHL inactivation and
lifestyle risk factors in renal-cell carcinoma from central and eastern
Europe
SO CANCER LETTERS
LA English
DT Article
DE TP53 mutations; VHL; EGFR; Cancer; Renal carcinoma
ID TUMOR-SUPPRESSOR GENE; P53 EXPRESSION; CANCER; PVHL; RNA
AB Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Szymanska, K.; Le Calvez-Kelm, F.; Villar, S.; Boffetta, P.; Hainaut, P.; Brennan, P.] Int Agcy Res Canc, F-69008 Lyon, France.
[Moore, L. E.; Rothman, N.; Chow, W. H.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Waldman, F.; Jaeger, E.] Univ Calif San Francisco, UCSF Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Waterboer, T.] German Canc Res Ctr, Infect & Canc Program, Heidelberg, Germany.
[Foretova, L.; Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, V.; Kollarova, H.] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic.
[Zaridze, D.; Matveev, V.] Russian Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Mates, D.] Inst Publ Hlth, Bucharest, Romania.
[Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Holcatova, I.; Bencko, V.] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
RP Brennan, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69008 Lyon, France.
EM gep@iarc.fr
RI Pawlita, Labor/C-9720-2011; Zaridze, David/K-5605-2013; Hainaut, Pierre
/B-6018-2012; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska,
Neonila/F-7190-2010; Waterboer, Tim/G-1252-2010;
OI Hainaut, Pierre /0000-0002-1303-1610; mates, dana/0000-0002-6219-9807;
Pawlita, Michael/0000-0002-4720-8306
FU European Commission [IC15-CT98-0332]; National Cancer Institute, NIH
[CA102600]; International Agency for Research on Cancer
FX This work was supported by a Grant from the European Commission's
INCO-COPERNICUS Program (Contract IC15-CT98-0332) and in part by the
Intramural Research Program of the National Cancer Institute, NIH
(Contract CA102600, EJ).; Katarzyna Szymanska undertook the work
reported in this paper during the tenure of a Postdoctoral Fellowship
awarded by the International Agency for Research on Cancer.
NR 19
TC 11
Z9 12
U1 0
U2 0
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 JUL 1
PY 2010
VL 293
IS 1
BP 92
EP 98
DI 10.1016/j.canlet.2009.11.024
PG 7
WC Oncology
SC Oncology
GA 602RG
UT WOS:000278155900011
PM 20137853
ER
PT J
AU Gheeya, J
Johansson, P
Chen, QR
Dexheimer, T
Metaferia, B
Song, YK
Wei, JS
He, JB
Pommier, Y
Khan, J
AF Gheeya, Jinesh
Johansson, Peter
Chen, Qing-Rong
Dexheimer, Thomas
Metaferia, Belhu
Song, Young K.
Wei, Jun S.
He, Jianbin
Pommier, Yves
Khan, Javed
TI Expression profiling identifies epoxy anthraquinone derivative as a DNA
topoisomerase inhibitor
SO CANCER LETTERS
LA English
DT Article
DE Neuroblastoma; Anti-cancer drug; Microarray; cMAP; Topoisomerase; EAD
ID I INHIBITORS; KAPPA-B; NEUROBLASTOMA; CLEAVAGE; HELENALIN; INDUCTION;
CANCER; CELLS
AB To discover novel drugs for neuroblastoma treatment, we have previously screened a panel of drugs and identified 30 active agents against neuroblastoma cells. Here we performed microarray gene expression analysis to monitor the impact of these agents on a neuroblastoma cell line and used the connectivity map (cMAP) to explore putative mechanism of action of unknown drugs. We first compared the expression profiles of 10 compounds shared in both our dataset and cMAP database and observed the high connectivity scores for 7 of 10 matched drugs regardless of the differences of cell lines utilized. The screen of cMAP for uncharacterized drugs indicated the signature of Epoxy anthraquinone derivative (EAD) matched the profiles of multiple known DNA targeted agents (topoisomerase I/II inhibitors, DNA intercalators. and DNA alkylation agents) as predicted by its structure. Similar result was obtained by querying against our internal NB-cMAP (http://pob.abcc.ncifcrf.gov/cgi-bin/cMAP), a database containing the profiles of 30 active drugs. These results suggest that Epoxy anthraquinone derivative may inhibit neuroblastoma cells by targeting DNA replication inhibition. Experimental data also demonstrate that Epoxy anthraquinone derivative indeed induces DNA double-strand breaks through DNA alkylation and inhibition of topoisomerase activity. Our study indicates that Epoxy anthraquinone derivative may be a novel DNA topoisomerase inhibitor that can be potentially used for treatment of neuroblastoma or other cancer patients. Published by Elsevier Ireland Ltd.
C1 [Gheeya, Jinesh; Johansson, Peter; Chen, Qing-Rong; Metaferia, Belhu; Song, Young K.; Wei, Jun S.; He, Jianbin; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD USA.
[Dexheimer, Thomas; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Khan, J (reprint author), NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD USA.
EM khanjav@mail.nih.gov
RI Khan, Javed/P-9157-2014; Johansson, Peter/K-1053-2014;
OI Khan, Javed/0000-0002-5858-0488; Johansson, Peter/0000-0001-7015-5452;
Gheeya, Jinesh/0000-0002-5246-6262
FU NIH, Center for Cancer Research, National Cancer Institute
FX We thank Sophic Systems Alliance (East Falmouth, MA) for helping to
develop NB-cMAP database. We thank Drs. Adam Cheuk and Patricia Tsang
for their technical assistance in cell viability assay. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
government. This work was supported by the NIH Intramural Program,
Center for Cancer Research, National Cancer Institute.
NR 25
TC 16
Z9 17
U1 2
U2 5
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 JUL 1
PY 2010
VL 293
IS 1
BP 124
EP 131
DI 10.1016/j.canlet.2010.01.004
PG 8
WC Oncology
SC Oncology
GA 602RG
UT WOS:000278155900015
PM 20133050
ER
PT J
AU Roth, MJ
Katki, HA
Wei, WQ
Qiao, YL
Bagni, R
Wang, GQ
Whitby, D
Dong, ZW
Gail, MH
Limburg, PJ
Giffen, CA
Taylor, PR
Dawsey, SM
AF Roth, Mark J.
Katki, Hormuzd A.
Wei, Wen-Qiang
Qiao, You-Lin
Bagni, Rachel
Wang, Guo-Qing
Whitby, Denise
Dong, Zhi-Wei
Gail, Mitchell H.
Limburg, Paul J.
Giffen, Carol A.
Taylor, Philip R.
Dawsey, Sanford M.
TI Serum Cytokine Analysis in a Positive Chemoprevention Trial: Selenium,
Interleukin-2, and an Association with Squamous Preneoplastic Disease
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID REGULATORY T-CELLS; RISK CHINESE POPULATION; ESOPHAGEAL CANCER;
COLORECTAL-CANCER; PERIPHERAL-BLOOD; GENE-EXPRESSION; IMMUNE-RESPONSE;
LINXIAN; DYSPLASIA; SELENOMETHIONINE
AB This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that, among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine downregulated interleukin (IL)-2 by 9% (P = 0.04), whereas celecoxib downregulated IL-7 by 11% (P = 0.006) and upregulated IL-13 by 17% (P = 0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall [odds ratio (OR), 1.47; P = 0.03] and among those with mild dysplasia at t0 (OR, 2.53; P = 0.001). An increase in IL-2 tertile from baseline to t10 was also nonsignificantly associated with worsening dysplasia for all participants (OR, 1.32; P = 0.098) and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR, 2.0; P = 0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR, 2.52; P = 0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, whereas celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10-month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect in reducing the levels of IL-2. Cancer Prev Res; 3(7); 810-7. (C) 2010 AACR.
C1 [Roth, Mark J.; Dawsey, Sanford M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Katki, Hormuzd A.; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wei, Wen-Qiang; Qiao, You-Lin; Wang, Guo-Qing; Dong, Zhi-Wei] Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100037, Peoples R China.
[Bagni, Rachel; Whitby, Denise] NCI, AIDS & Canc Virus Program, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA.
[Limburg, Paul J.] Mayo Clin, Ctr Canc, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Giffen, Carol A.] Informat Management Serv Inc, Silver Spring, MD USA.
RP Roth, MJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320,MSC 7232, Bethesda, MD 20892 USA.
EM mr166i@nih.gov
RI Qiao, You-Lin/B-4139-2012; Katki, Hormuzd/B-4003-2015
OI Qiao, You-Lin/0000-0001-6380-0871;
FU National Cancer Institute, NIH
FX Intramural Research Program of the National Cancer Institute, NIH. 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 45
TC 0
Z9 0
U1 0
U2 19
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUL
PY 2010
VL 3
IS 7
BP 810
EP 817
DI 10.1158/1940-6207.CAPR-09-0269
PG 8
WC Oncology
SC Oncology
GA 621EJ
UT WOS:000279556900003
PM 20587703
ER
PT J
AU Pinsky, PF
Fleshman, J
Mutch, M
Rall, C
Charabaty, A
Seligson, D
Dry, S
Umar, A
Schoen, RE
AF Pinsky, Paul F.
Fleshman, James
Mutch, Matt
Rall, Christopher
Charabaty, Aline
Seligson, David
Dry, Sarah
Umar, Asad
Schoen, Robert E.
TI One Year Recurrence of Aberrant Crypt Foci
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ADENOMA PREVENTION; COLONOSCOPY; HISTORY
AB Aberrant crypt foci (ACF) are putative precursors of colorectal adenomas and have been postulated as a potential biomarker for colorectal cancer. Few studies have followed subjects after ACF removal to monitor recurrence. Subjects enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were recruited for a study of ACF. A standardized protocol using magnified endoscopy and mucosal staining with methylene blue was implemented to detect rectal ACF. After removal of all baseline ACF, subjects returned 1 year later and recurrent ACF were observed and biopsied. A total of 434 of 505 (86%) subjects observed at baseline returned for the year 1 exam. The mean number of ACF at year 1 was strongly correlated with the number at baseline; subjects with 0, 1, 2 to 3, 4 to 6, and 7+ ACF at baseline had a mean of 1.2, 1.4, 1.7, 3.0, and 5.5 ACF, respectively, at year 1. ACF prevalence and mean count at year 1 (61% and 1.93, respectively), were only slightly lower than the corresponding values at year 0 (69% and 2.25, respectively). The locations of ACF at year 1 and baseline were significantly correlated. Of 96 ACF assessed for histology, 70 (73%) were hyperplastic and none were dysplastic. After removal of ACF at baseline, ACF counts 1 year later were only slightly reduced and were significantly correlated with the baseline ACF count. The results of this study do not support a role for ACF in clinical practice. Cancer Prev Res; 3(7); 839-43. (C) 2010 AACR.
C1 [Pinsky, Paul F.; Umar, Asad] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Fleshman, James; Mutch, Matt] Washington Univ, St Louis, MO USA.
[Rall, Christopher] Marshfield Res Clin, Marshfield, WI USA.
[Charabaty, Aline] Georgetown Univ, Washington, DC USA.
[Seligson, David; Dry, Sarah] Univ Calif Los Angeles, Los Angeles, CA USA.
[Schoen, Robert E.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 15
TC 8
Z9 8
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUL
PY 2010
VL 3
IS 7
BP 839
EP 843
DI 10.1158/1940-6207.CAPR-09-0257
PG 5
WC Oncology
SC Oncology
GA 621EJ
UT WOS:000279556900006
PM 20570885
ER
PT J
AU Guigon, CJ
Fozzatti, L
Lu, CX
Willingham, MC
Cheng, SY
AF Guigon, Celine J.
Fozzatti, Laura
Lu, Changxue
Willingham, Mark C.
Cheng, Sheue-yann
TI Inhibition of mTORC1 signaling reduces tumor growth but does not prevent
cancer progression in a mouse model of thyroid cancer
SO CARCINOGENESIS
LA English
DT Article
ID HORMONE-BETA-RECEPTOR; MAMMALIAN TARGET; AKT ACTIVATION; BREAST-CANCER;
CYCLIN D1; PTEN LOSS; CARCINOMA; RAPAMYCIN; PATHWAY; PHOSPHORYLATION
AB Selective drugs targeting dysregulated oncogenic pathways are promising cancer therapies. Because the mammalian target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in human follicular thyroid cancer (FTC), we hypothesized that its inhibition could block cancer development and progression. We, therefore, analyzed the effect of a treatment with a specific mTORC1 inhibitor (RAD001) in a faithful mouse model of FTC with constitutive mTORC1 activation (TR beta(PV/PV)Pten(+/-) mice). The treatment did not prevent capsular and vascular invasion of the thyroid and the occurrence of lung metastasis. However, it substantially decelerated thyroid tumor growth, thereby prolonging TR beta(PV/PV)Pten(+/-) mouse life span. RAD001 efficiently inhibited mTORC1 activity, as shown by the reduced phosphorylation of its downstream targets involved in the activity of the translation machinery, such as ribosomal S6 kinase (p70(S6K)), eukaryotic translation initiation factor 4E binding protein (4E-BP1) and the eukaryotic translation initiation factors eIF-4B and eIF-4G. Whereas mTORC1 signaling inhibition did not alter cell apoptosis, it induced a significant decrease in cell proliferation that was associated with the reduced abundance and altered activity of key regulators of cell cycle progression. Altogether, our data indicate that mTORC1 signaling plays a major role in the integration of the mitogenic signal in FTC. Therefore, our preclinical study with a relevant mouse model of FTC demonstrates for the first time that RAD001 efficaciously stabilizes cancer growth although it does not prevent its fatal outcome. In conclusion, our work underscores that in the treatment of FTC patients, RAD001 can only be used in combination with drugs and therapies inducing tumor shrinkage and blocking metastasis.
C1 [Guigon, Celine J.; Fozzatti, Laura; Lu, Changxue; Cheng, Sheue-yann] Natl Canc Inst, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA.
RP Cheng, SY (reprint author), Natl Canc Inst, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
NR 43
TC 14
Z9 15
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2010
VL 31
IS 7
BP 1284
EP 1291
DI 10.1093/carcin/bgq059
PG 8
WC Oncology
SC Oncology
GA 620BD
UT WOS:000279473100016
PM 20299527
ER
PT J
AU Hur, W
Rhim, H
Jung, CK
Kim, JD
Bae, SH
Jang, JW
Yang, JM
Oh, ST
Kim, DG
Wang, HJ
Lee, SB
Yoon, SK
AF Hur, Wonhee
Rhim, Hyangshuk
Jung, Chan Kwon
Kim, Jin Dong
Bae, Si Hyun
Jang, Jeong Won
Yang, Jin Mo
Oh, Seong-Taek
Kim, Dong Goo
Wang, Hee Jung
Lee, Sean Bong
Yoon, Seung Kew
TI SOX4 overexpression regulates the p53-mediated apoptosis in
hepatocellular carcinoma: clinical implication and functional analysis
in vitro
SO CARCINOGENESIS
LA English
DT Article
ID SEX-DETERMINING REGION; TUMOR-SUPPRESSOR GENE; PROSTATE-CANCER CELLS;
HMG-BOX PROTEIN; P53 GENE; TRANSCRIPTIONAL ACTIVATOR; COLORECTAL-CANCER;
DNA-DAMAGE; EXPRESSION; IDENTIFICATION
AB Background and aims: The underlying molecular mechanisms of hepatocellular carcinoma (HCC) remain poorly understood due to its complex development process. The human T cell-specific transcription factor sex-determining region Y-related high-mobility group (HMG) box 4 (SOX4) has been linked to development and tumorigenesis. In this study, we characterized the roles of SOX4 in regulation of the p53 transcription activity and evaluated the expression patterns and prognostic value of the transcription factor SOX4 in HCC. Methods: The expression levels of human SOX4 were examined in HCC samples obtained from 58 patients having curative partial hepatectomy. The interaction and effects of SOX4 on the p53 pathway were assessed in HCC cell lines. Luciferase reporter assay to examine p53-mediated transcription of target genes was performed. The association of SOX4 expression level with tumor recurrence and overall survival was evaluated. Results: We showed that the HMG box domain of SOX4 interacted with p53, resulting in the inhibition of p53-mediated transcription by the Bax promoter. More importantly, SOX4 overexpression led to a significant repression of p53-induced Bax expression and subsequent repression of p53-mediated apoptosis induced by gamma-irradiation. In clinicopathological analysis, nuclear overexpression of SOX4 was observed in 37 out of 58 (63.8%) HCC samples, and this correlated with diminished risk of recurrence (P = 0.014) and improved overall survival time (P = 0.045) in HCC patients. Conclusion: These results suggest that SOX4 contributes to hepatocarcinogenesis by inhibiting p53-mediated apoptosis and that its overexpression might be a useful prognostic marker for survival after surgical resection.
C1 [Hur, Wonhee; Kim, Jin Dong; Bae, Si Hyun; Jang, Jeong Won; Yang, Jin Mo; Yoon, Seung Kew] Catholic Univ Korea, Dept Internal Med, Seoul 137701, South Korea.
[Hur, Wonhee; Kim, Jin Dong; Bae, Si Hyun; Jang, Jeong Won; Yang, Jin Mo; Yoon, Seung Kew] Catholic Univ Korea, WHO Collaborating Ctr Viral Hepatitis, Seoul 137701, South Korea.
[Rhim, Hyangshuk] Catholic Univ Korea, Catholic Res Inst Med Sci, Res Inst Mol Genet, Seoul 137701, South Korea.
[Jung, Chan Kwon] Catholic Univ Korea, Dept Hosp Pathol, Seoul 137701, South Korea.
[Oh, Seong-Taek; Kim, Dong Goo] Catholic Univ Korea, Dept Surg, Seoul 137701, South Korea.
[Wang, Hee Jung] Ajou Univ, Sch Med, Dept Surg, Suwon 443721, South Korea.
[Lee, Sean Bong] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Yoon, SK (reprint author), Catholic Univ Korea, Dept Internal Med, Seoul 137701, South Korea.
EM yoonsk@catholic.ac.kr
OI Kim, Jin Dong/0000-0001-9660-6303
FU Ministry of Science and Technology, Korea [FG-08-12-05]
FX 21C Frontier Functional Human Genome Project from the Ministry of
Science and Technology, Korea (FG-08-12-05).
NR 53
TC 42
Z9 45
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2010
VL 31
IS 7
BP 1298
EP 1307
DI 10.1093/carcin/bgq072
PG 10
WC Oncology
SC Oncology
GA 620BD
UT WOS:000279473100018
PM 20400479
ER
PT J
AU Gonzalez, FJ
Conney, AH
AF Gonzalez, Frank J.
Conney, Allan H.
TI Harry V. Gelboin, 1929-2010 OBITUARY
SO CARCINOGENESIS
LA English
DT Biographical-Item
C1 [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Conney, Allan H.] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan L Cullman Lab Canc Res, Piscataway, NJ 08854 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2010
VL 31
IS 7
BP 1308
EP 1309
DI 10.1093/carcin/bgq093
PG 2
WC Oncology
SC Oncology
GA 620BD
UT WOS:000279473100019
ER
PT J
AU Chin-Dusting, JPF
Vaisman, BL
Khong, SML
Remaley, AT
Andrews, KL
AF Chin-Dusting, J. P. F.
Vaisman, B. L.
Khong, S. M. L.
Remaley, A. T.
Andrews, K. L.
TI Overexpression of arginase II worsens endothelial dysfunction and
atherosclerosis while arginase I overexpression may have
cardioprotective effects
SO CARDIOVASCULAR RESEARCH
LA English
DT Meeting Abstract
CT Conference on Frontiers in Cardiovascular Biology
CY JUL 16-19, 2010
CL Berlin, GERMANY
C1 [Chin-Dusting, J. P. F.; Khong, S. M. L.; Andrews, K. L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Vaisman, B. L.; Remaley, A. T.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL
PY 2010
VL 87
SU 1
BP S130
EP S131
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 653RJ
UT WOS:000282114100399
ER
PT J
AU Tripathi, BK
Zelenka, PS
AF Tripathi, Brajendra K.
Zelenka, Peggy S.
TI Cdk5 A regulator of epithelial cell adhesion and migration
SO CELL ADHESION & MIGRATION
LA English
DT Article
DE Cdk5; Src; Rho; stress fibers; epithelial cells; cell adhesion; cell
migration
AB Cell adhesion is a fundamental property of epithelial cells required for anchoring, migration and survival. During cell migration, the formation and disruption of adhesion sites is stringently regulated by integration of multiple, sequential signals acting in distinct regions of the cell. Recent findings implicate cyclin dependent kinase 5 (Cdk5) in the signaling pathways that regulate cell adhesion and migration of a variety of cell types. Experiments with epithelial cell lines indicate that Cdk5 activity exerts its effects by limiting Src activity in regions where Rho activity is required for stress fiber contraction and by phosphorylating the talin head to stabilize nascent focal adhesions. Both pathways regulate cell migration by increasing adhesive strength.
C1 [Tripathi, Brajendra K.; Zelenka, Peggy S.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Zelenka, PS (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM zelenkap@nei.nih.gov
NR 29
TC 8
Z9 8
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6918
J9 CELL ADHES MIGR
JI Celll Adhes. Migr.
PD JUL-SEP
PY 2010
VL 4
IS 3
BP 333
EP 336
DI 10.4161/cam.4.3.11131
PG 4
WC Cell Biology
SC Cell Biology
GA V21VJ
UT WOS:000208234800002
PM 20190570
ER
PT J
AU Schuster, A
Schilling, T
De Laurenzi, V
Koch, AF
Seitz, S
Staib, F
Teufel, A
Thorgeirsson, SS
Galle, PR
Melino, G
Stremmel, W
Krammer, PH
Muller, M
AF Schuster, Andre
Schilling, Tobias
De Laurenzi, Vincenzo
Koch, Andreas F.
Seitz, Sarah
Staib, Frank
Teufel, Andreas
Thorgeirsson, Snorri S.
Galle, Peter R.
Melino, Gerry
Stremmel, Wolfgang
Krammer, Peter H.
Mueller, Martina
TI Delta Np73 beta is oncogenic in hepatocellular carcinoma by blocking
apoptosis signaling via death receptors and mitochondria
SO CELL CYCLE
LA English
DT Article
DE apoptosis; hepatocellular carcinoma; therapy response; dominant negative
p73; p53 family
ID TUMOR-SUPPRESSOR P53; INDUCED CELL-DEATH; WILD-TYPE P53; BINDING-SITE;
DNA-DAMAGE; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; P73; GENE; P63
AB Background and Aims: p73 belongs to the p53 family of transcription factors known to regulate cell cycle and apoptosis. The Trp73 gene has two promoters that drive the expression of two major p73 isoform subfamilies: TA and Delta N. In general, TAp73 isoforms show proapoptotic activities, whereas members of the N-terminally truncated (Delta N) p73 subfamily that lack the transactivation domain show antiapoptotic functions. We found that upregulation of Delta Np73 in hepatocellular carcinoma (HCC) correlated with reduced survival. Here, we investigated the molecular mechanisms accounting for the oncogenic role of Delta Np73 in HCC.
Results:Delta Np73 beta can directly interfere with the transcriptional activation function of the TA (containing the transactivation domain) isoforms of the p53 family and consequently inhibit transactivation of proapoptotic target genes. Interference of Delta Np73 beta with apoptosis-/chemosensitivity takes place at several levels of apoptosis signaling. Delta Np73 beta negatively regulates the genes encoding for the death receptors CD95, TNF-R1, TRAIL-R2 and TNFRSF18. Furthermore, Delta Np73 beta represses the genes encoding caspase-2, -3, -6, -8 and -9.
Concomitantly, Delta Np73 beta inhibits apoptosis emanating from mitochondria. Conclusions: Thus, Delta Np73 expression in HCC selects against both the death receptor and the mitochondrial apoptosis activity of the TA isoforms. Our data suggest that Delta Np73 isoforms repress apoptosis-related genes of the extrinsic and intrinsic apoptosis signaling pathways thereby contributing to chemoresistance. The clinical importance of these data is evidenced by our finding that the Delta Np73 beta target gene signature can predict the prognosis of patients suffering from HCC.
C1 [Schuster, Andre; Koch, Andreas F.; Seitz, Sarah; Stremmel, Wolfgang; Mueller, Martina] Univ Heidelberg Hosp, Dept Internal Med 4, Heidelberg, Germany.
[Schilling, Tobias] Univ Heidelberg Hosp, Dept Internal Med & Clin Chem 1, Heidelberg, Germany.
[De Laurenzi, Vincenzo] Univ G dAnnunzio, Fdn G DAnnunzio CeSI, Dipartimento Sci Biomed, Chieti, Italy.
[Staib, Frank; Teufel, Andreas; Galle, Peter R.] Univ Hosp, Dept Internal Med 1, Mainz, Germany.
[Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Melino, Gerry] Univ Rome, Dept Expt Med & Biochem Sci, IDI IRCCS, Biochem Lab, Rome, Italy.
[Melino, Gerry] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England.
[Krammer, Peter H.] German Canc Res Ctr, Tumor Immunol Program, Heidelberg, Germany.
RP Muller, M (reprint author), Univ Heidelberg Hosp, Dept Internal Med 4, Heidelberg, Germany.
EM Martina_Mueller-Schilling@med.uni-heidelberg.de
FU Deutsche Forschungsgemeinschaft; Transregional Collaborative Research
Centre [SFB/TRR77]; Tumorzentrum Heidelberg/Mannheim; Helmholtz
Association; Forschungsschwerpunktrogramm Baden-Wurttemberg; AIRC
FX This work was supported by grants of the Deutsche
Forschungsgemeinschaft, Transregional Collaborative Research Centre
SFB/TRR77 to M. M. and P. H. K. the Tumorzentrum Heidelberg/Mannheim to
M. M. and P. H. K. the Helmholtz Alliance on Immunotherapy of Cancer
funded by the Initiative and Networking Fund of the Helmholtz
Association to M. M. and P. H. K. the Forschungsschwerpunktrogramm
Baden-Wurttemberg to M. M., and the AIRC to V. D. L.
NR 50
TC 18
Z9 18
U1 1
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2010
VL 9
IS 13
BP 2629
EP 2639
DI 10.4161/cc.9.13.12110
PG 11
WC Cell Biology
SC Cell Biology
GA 642IX
UT WOS:000281205400037
PM 20581467
ER
PT J
AU Tomashevski, A
Webster, DR
Grammas, P
Gorospe, M
Kruman, II
AF Tomashevski, A.
Webster, D. R.
Grammas, P.
Gorospe, M.
Kruman, I. I.
TI Cyclin-C-dependent cell-cycle entry is required for activation of
non-homologous end joining DNA repair in postmitotic neurons
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE neuron; DNA repair; cell cycle; DNA damage; apoptosis
ID DOUBLE-STRAND BREAKS; PROTEIN-KINASE; ATAXIA-TELANGIECTASIA; CATALYTIC
SUBUNIT; RAT NEURONS; DEATH; APOPTOSIS; PATHWAY; DAMAGE; EXPRESSION
AB It is commonly believed that neurons remain in G(0) phase of the cell cycle indefinitely. Cell-cycle re-entry, however, is known to contribute to neuronal apoptosis. Moreover, recent evidence demonstrates the expression of cell-cycle proteins in differentiated neurons under physiological conditions. The functional roles of such expression remain unclear. Since DNA repair is generally attenuated by differentiation in most cell types, the cell-cycle-associated events in postmitotic cells may reflect the need to re-enter the cell cycle to activate DNA repair. We show that cyclin-C-directed, pRb-dependent G(0) exit activates the non-homologous end joining pathway of DNA repair (NHEJ) in postmitotic neurons. Using RNA interference, we found that abrogation of cyclin-C-mediated exit from G(0) compromised DNA repair but did not initiate apoptosis. Forced G(1) entry combined with prevention of G(1)-->S progression triggered NHEJ activation even in the absence of DNA lesions, but did not induce apoptosis in contrast to unrestricted progression through G(1)-->S. We conclude that G(0)-->G(1) transition is functionally significant for NHEJ repair in postmitotic neurons. These findings reveal the importance of cell-cycle activation for controlling both DNA repair and apoptosis in postmitotic neurons, and underline the particular role of G(1)-->S progression in apoptotic signaling, providing new insights into the mechanisms of DNA damage response (DDR) in postmitotic neurons. Cell Death and Differentiation (2010) 17, 1189-1198; doi:10.1038/cdd.2009.221; published online 29 January 2010
C1 [Tomashevski, A.; Grammas, P.; Kruman, I. I.] Texas Tech Univ, Hlth Sci Ctr, Garrison Inst Aging, Lubbock, TX 79430 USA.
[Webster, D. R.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA.
[Grammas, P.; Kruman, I. I.] Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA.
[Gorospe, M.] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA.
RP Kruman, II (reprint author), Texas Tech Univ, Hlth Sci Ctr, Garrison Inst Aging, Lubbock, TX 79430 USA.
EM inna.kruman@ttuhsc.edu
FU Garrison Institute on Aging, TTUHSC; NIA-IRP, NIH
FX We thank Raul Perez-Olle for helpful discussions and P Makhov for the
pGL3 basic vector. This work was supported by the Garrison Institute on
Aging, TTUHSC. MG was funded by the NIA-IRP, NIH.
NR 40
TC 15
Z9 16
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JUL
PY 2010
VL 17
IS 7
BP 1189
EP 1198
DI 10.1038/cdd.2009.221
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 610IU
UT WOS:000278726100013
PM 20111042
ER
PT J
AU Li, XR
AF Li, Xuri
TI VEGF-B: a thing of beauty
SO CELL RESEARCH
LA English
DT Editorial Material
ID GROWTH-FACTOR-B; MYOCARDIAL HYPERTROPHY; ENDOTHELIAL-CELLS;
ANGIOGENESIS; MICE; RECEPTOR-1; EXPRESSION; SURVIVAL; ACID
C1 NEI, NIH, Rockville, MD 20852 USA.
RP Li, XR (reprint author), NEI, NIH, Rockville, MD 20852 USA.
EM lixur@nei.nih.gov
FU Intramural NIH HHS [Z01 EY000447-01, Z99 EY999999]
NR 15
TC 9
Z9 12
U1 0
U2 7
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD JUL
PY 2010
VL 20
IS 7
BP 741
EP 744
DI 10.1038/cr.2010.77
PG 4
WC Cell Biology
SC Cell Biology
GA 627YB
UT WOS:000280079500003
PM 20531376
ER
PT J
AU Gan, QA
Chepelev, I
Wei, G
Tarayrah, L
Cui, KR
Zhao, KJ
Chen, X
AF Gan, Qiang
Chepelev, Iouri
Wei, Gang
Tarayrah, Lama
Cui, Kairong
Zhao, Keji
Chen, Xin
TI Dynamic regulation of alternative splicing and chromatin structure in
Drosophila gonads revealed by RNA-seq
SO CELL RESEARCH
LA English
DT Article
DE Transcription; alternative splicing; differentiation; testis; ovary;
Drosophila
ID GERMLINE STEM-CELLS; SOMATIC SEXUAL-DIFFERENTIATION; BAG-OF-MARBLES;
GENE-EXPRESSION; X-CHROMOSOME; SELF-RENEWAL; EXUPERANTIA GENE; H3K4
METHYLATION; BINDING-PROTEIN; MELANOGASTER
AB Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type (WT) gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles (bam) mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Drosophila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. The GEO accession number for the raw and analyzed RNA-seq data is GSE16960.
C1 [Gan, Qiang; Tarayrah, Lama; Chen, Xin] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Chepelev, Iouri; Wei, Gang; Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Chen, X (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles St, Baltimore, MD 21218 USA.
EM xchen32@jhu.edu
RI Wei, Gang/A-3291-2011; Gan, Qiang/K-9605-2013
FU March of Dimes Foundation [05-FY09-88]; NICHD, NIH [R00HD055052]; Edward
Mallinckrodt, Jr. Foundation; Johns Hopkins University; Division of
Intramural Research, the National Heart, Lung and Blood Institute, NIH
FX We would like to thank Drs Allan Spradling (Carnegie Institution, USA),
Karen Beemon and Mark Van Doren (The Johns Hopkins University, USA), and
Chen lab members for critical readings and suggestions on the
manuscript. We thank Dr Dustin E Schones (National Institutes of Health,
USA) for help to set up the initial data analysis pipeline, and Caitlin
Choi and Ankit Vartak for technical assistance with the PCR experiments.
This work is supported in part by Research Grant No. 05-FY09-88 from the
March of Dimes Foundation, the R00HD055052 NIH Pathway to Independence
Award from NICHD, the 49th Mallinckrodt Scholar Award from the Edward
Mallinckrodt, Jr. Foundation, support from the Johns Hopkins University
(XC) and the Division of Intramural Research, the National Heart, Lung
and Blood Institute, NIH (KZ).
NR 107
TC 49
Z9 55
U1 1
U2 21
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD JUL
PY 2010
VL 20
IS 7
BP 763
EP 783
DI 10.1038/cr.2010.64
PG 21
WC Cell Biology
SC Cell Biology
GA 627YB
UT WOS:000280079500006
PM 20440302
ER
PT J
AU Secundino, N
Kimblin, N
Peters, NC
Lawyer, P
Capul, AA
Beverley, SM
Turco, SJ
Sacks, D
AF Secundino, Nagila
Kimblin, Nicola
Peters, Nathan C.
Lawyer, Phillip
Capul, Althea A.
Beverley, Stephen M.
Turco, Salvatore J.
Sacks, David
TI Proteophosphoglycan confers resistance of Leishmania major to midgut
digestive enzymes induced by blood feeding in vector sand flies
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID PHLEBOTOMUS-PAPATASI; VIRULENCE FACTOR; LIPOPHOSPHOGLYCAN; DONOVANI;
PHOSPHOGLYCAN; EXPRESSION; PARASITES; PROMASTIGOTES; TRANSMISSION;
PURIFICATION
AB Leishmania synthesize abundant phosphoglycan-containing molecules made up of [Gal-Man-PO(4)] repeating units, including the surface lipophosphoglycan (LPG), and the surface and secreted proteophosphoglycan (PPG). The vector competence of Phlebotomus duboscqi and Lutzomyia longipalpis sand flies was tested using L. major knockout mutants deficient in either total phosphoglycans (lpg2- or lpg5A-/5B-) or LPG alone (lpg1-) along with their respective gene add-back controls. Our results confirm that LPG, the major cell surface molecule of Leishmania promastigotes known to mediate attachment to the vector midgut, is necessary to prevent the loss of infection during excretion of the blood meal remnants from a natural vector, P. duboscqi, but not an unnatural vector, L. longipalpis. Midgut digestive enzymes induced by blood feeding pose another potential barrier to parasite survival. Our results show that 36-72 h after the infective feed, all parasites developed well except the lpg2- and lpg5A-/5B- mutants, which showed significantly reduced survival and growth. Protease inhibitors promoted the early survival and growth of lpg2- in the blood meal. PPG was shown to be the key molecule conferring resistance to midgut digestive enzymes, as it prevented killing of lpg2- promastigotes exposed to midgut lysates prepared from blood-fed flies. The protection was not associated with inhibition of enzyme activities, but with cell surface acquisition of the PPG, which appears to function similar to mammalian mucins to protect the surface of developing promastigotes against proteolytic damage.
C1 [Secundino, Nagila; Kimblin, Nicola; Peters, Nathan C.; Lawyer, Phillip; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Capul, Althea A.; Beverley, Stephen M.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Turco, Salvatore J.] Univ Kentucky, Med Ctr, Dept Biochem, Lexington, KY 40536 USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
OI Beverley, Stephen/0000-0001-5319-0811
FU NIAID, NIH [AI031078]
FX This research was supported in part by the Intramural Research Program
of the NIAID, NIH, and in part by NIAID Grant Support (SMB and SJT
AI031078).
NR 37
TC 17
Z9 17
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD JUL
PY 2010
VL 12
IS 7
BP 906
EP 918
DI 10.1111/j.1462-5822.2010.01439.x
PG 13
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 607PS
UT WOS:000278518900005
PM 20088949
ER
PT J
AU Lafdil, F
Miller, AM
Ki, SH
Gao, B
AF Lafdil, Fouad
Miller, Andrew M.
Ki, Sung Hwan
Gao, Bin
TI Th17 cells and their associated cytokines in liver diseases
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Review
DE IL-17; IL-22; hepatitis; alcoholic liver disease; liver cancer
ID REGULATORY T-CELLS; HEPATOCELLULAR-CARCINOMA PATIENTS; CHRONIC
HEPATITIS-B; C VIRUS-INFECTION; NONALCOHOLIC STEATOHEPATITIS; AUTOIMMUNE
CHOLANGITIS; MEDIATED HEPATITIS; INNATE IMMUNITY; INTERLEUKIN-17; INJURY
AB T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria as well as in the pathogenesis of autoimmune disease. The functions of Th17 cells are mediated via the production of several cytokines including interleukin (IL)-17 and IL-22. Recent studies show that the frequency of IL-17(+) cells is significantly elevated in a variety of chronic liver diseases including alcoholic liver disease, viral hepatitis and hepatocellular carcinoma. IL-17 receptor is expressed virtually on all types of liver cells, while IL-22 receptor expression is restricted to epithelial cells including hepatocytes in the liver. IL-17 seems to play an important role in inducing liver inflammation via stimulating multiple types of liver nonparenchymal cells to produce proinflammatory cytokines and chemokines, while IL-22 appears to be an important factor in promoting hepatocyte survival and proliferation. Cellular & Molecular Immunology (2010) 7, 250-254; doi:10.1038/cmi.2010.5; published online 22 March 2010
C1 [Lafdil, Fouad; Miller, Andrew M.; Ki, Sung Hwan; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Lafdil, Fouad] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France.
[Lafdil, Fouad] Univ Paris 12, Fac Med, Creteil, France.
RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
FU NIAAA, NIH
FX This work was supported by the intramural program of NIAAA, NIH.
NR 59
TC 48
Z9 61
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1672-7681
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JUL
PY 2010
VL 7
IS 4
BP 250
EP 254
DI 10.1038/cmi.2010.5
PG 5
WC Immunology
SC Immunology
GA 620GQ
UT WOS:000279487500002
PM 20305686
ER
PT J
AU Hu, GL
Liu, Y
Li, H
Zhao, DK
Yang, LQ
Shen, JG
Hong, XJ
Cao, XT
Wang, QQ
AF Hu, Guili
Liu, Yang
Li, Hong
Zhao, Dekuang
Yang, Liuqing
Shen, Jiangen
Hong, Xuejun
Cao, Xuetao
Wang, Qingqing
TI Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma
elicits a potent antitumor effect
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Article
DE adenovirus; B lymphoma; gene transfer; LIGHT/TNFSF14
ID NON-HODGKINS-LYMPHOMA; IMPROVES THERAPEUTIC-EFFICACY; IN-VIVO;
COSTIMULATORY FUNCTION; TUMOR IMMUNOGENICITY; ESTABLISHED TUMORS;
LYMPHOTOXIN-BETA; CD54 EXPRESSION; ICAM-1 CD54; LYMPHOCYTES
AB Here, we investigated the antitumor effect of adenovirus-mediated gene transfer of LIGHT, the tumor-necrosis factor (TNF) superfamily member also known as TNFSF14, in the murine A20 B-cell lymphoma. LIGHT gene modification resulted in upregulated expression of Fas and the accessory molecule-intercellular adhesion molecule-1 (ICAM-1) on A20 cells and led to enhanced A20 cell apoptosis. LIGHT-modified A20 cells effectively stimulated the proliferation of T lymphocytes and interferon (IFN)-gamma production in vitro. Immunization of BALB/c mice with a LIGHT-modified A20 cell vaccine efficiently elicited protective immunity against challenge with the parental tumor cell line. Adenovirus-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against pre-existing A20 cell lymphoma in BALB/c mice. This adenovirus-mediated LIGHT therapy induced substantial splenic natural killer (NK) and cytotoxic T lymphocyte (CTL) activity, enhanced tumor infiltration by inflammatory cells and increased chemokine expression of CC chemokine ligand 21 (CCL21), IFN-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig) from tumor tissues. Thus, adenovirus-mediated LIGHT therapy might have potential utility for the prevention and treatment of B-cell lymphoma. Cellular & Molecular Immunology (2010) 7, 296-305; doi:10.1038/cmi.2010.15; published online 26 April 2010
C1 [Hu, Guili; Liu, Yang; Zhao, Dekuang; Yang, Liuqing; Shen, Jiangen; Hong, Xuejun; Cao, Xuetao; Wang, Qingqing] Zhejiang Univ, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China.
[Li, Hong] NIEHS, Mol & Cellular Biol Grp, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Cao, Xuetao] Second Mil Med Univ, Inst Immunol, Shanghai, Peoples R China.
[Cao, Xuetao] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai, Peoples R China.
RP Wang, QQ (reprint author), Zhejiang Univ, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China.
EM wqq@zju.edu.cn
RI Zhao, Dekuang/H-5671-2015
OI Zhao, Dekuang/0000-0002-7251-2481
FU National Natural Science Foundation of China [30328011, 30872377];
National Basic Research Program of China [2004CB518802]; Science and
Technology Department of Zhejiang Province [2008C23044]
FX We thank Professor Yangxin Fu of The University of Chicago for the gift
of Ad LIGHT. This work was supported by grants from the National Natural
Science Foundation of China (30328011 and 30872377), the National Basic
Research Program of China (2004CB518802) and the Science and Technology
Department of Zhejiang Province (2008C23044). We would like to
acknowledge Jianping Pan and Dajing Xia for helpful suggestions and
discussions.
NR 36
TC 4
Z9 6
U1 0
U2 4
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JUL
PY 2010
VL 7
IS 4
BP 296
EP 305
DI 10.1038/cmi.2010.15
PG 10
WC Immunology
SC Immunology
GA 620GQ
UT WOS:000279487500009
PM 20418899
ER
PT J
AU Ito, Y
AF Ito, Yoichiro
TI Spiral column configuration for protein separation by high-speed
countercurrent chromatography
SO CHEMICAL ENGINEERING AND PROCESSING
LA English
DT Article
DE Configuration; Countercurrent chromatography; Coil planet centrifuge;
Spiral disk assembly; spiral tube assembly; protein separation; polymer
phase system
ID HYDRODYNAMIC BEHAVIOR; SOLVENT SYSTEMS; RESOLUTION; SUPPORT
AB of the stationary phase of aqueous-aqueous polymer phase systems is improved by a spiral column configuration which utilizes the radially acting centrifugal force along the spiral pitch to retain the heavier phase in the outer portion and the lighter phase in the inner portion of the spiral channel. For the separation of proteins which has low mass transfer rates, the system needs further modification of the separation channel to interrupt the laminar flow and enhance mixing of the two phases.
Two spiral column assemblies were developed, one using a disk with spiral grooves and the other, the spiral tube support which accommodates the multiple spiral layers made from a single piece of fluorinated plastic tubing. In the spiral disk assembly, the best protein separation is achieved by the mixer-settler system which vigorously mixes two phases by vibrating glass beads placed in every other section of barricaded spiral channel, while in the spiral tube assembly the partition efficiency of proteins is enhanced by compressing the tubing to interrupt the laminar flow of the mobile phase. In both systems protein samples were well resolved by choosing the suitable elution modes. Published by Elsevier B.V
C1 NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 23
TC 17
Z9 17
U1 1
U2 8
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0255-2701
J9 CHEM ENG PROCESS
JI Chem. Eng. Process.
PD JUL
PY 2010
VL 49
IS 7
SI SI
BP 782
EP 792
DI 10.1016/j.cep.2009.08.003
PG 11
WC Energy & Fuels; Engineering, Chemical
SC Energy & Fuels; Engineering
GA 653SN
UT WOS:000282117100018
PM 20823942
ER
PT J
AU Kozikowski, AP
Cho, SJ
Jensen, NH
Allen, JA
Svennebring, AM
Roth, BL
AF Kozikowski, Alan P.
Cho, Sung Jin
Jensen, Niels H.
Allen, John A.
Svennebring, Andreas M.
Roth, Bryan L.
TI HTS and Rational Drug Design to Generate a Class of 5-HT2C-Selective
Ligands for Possible Use in Schizophrenia
SO CHEMMEDCHEM
LA English
DT Article
DE 5-HT2C; CNS; drug discovery; medicinal chemistry; schizophrenia
ID SEROTONIN 5-HT2C RECEPTOR; ANTIOBESITY AGENTS; AGONISTS; BEHAVIOR;
COCAINE; OBESITY; MODELS; RATS; MICE
C1 [Kozikowski, Alan P.; Cho, Sung Jin; Svennebring, Andreas M.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Drug Discovery Program, Chicago, IL 60612 USA.
[Jensen, Niels H.; Allen, John A.; Roth, Bryan L.] Univ N Carolina, Div Med Chem & Nat Prod, Dept Pharmacol, Comprehens Canc Ctr,Med Sch,Ctr Neurobiol, Chapel Hill, NC 27599 USA.
[Jensen, Niels H.; Allen, John A.; Roth, Bryan L.] Univ N Carolina, Div Med Chem & Nat Prod, Dept Psychiat, Comprehens Canc Ctr,Med Sch,Ctr Neurobiol, Chapel Hill, NC 27599 USA.
[Jensen, Niels H.; Allen, John A.; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
RP Kozikowski, AP (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Drug Discovery Program, Chicago, IL 60612 USA.
EM kozikowa@uic.edu
RI Roth, Bryan/F-3928-2010; Allen, John/D-6141-2011;
OI zaraat, javad/0000-0001-5341-7481
FU NIH [R01 DA022317, R01 MH61887, N01 MH80032, U19 MH82441]; Korean
Government [KRF-2007-357-C00071]; NIDA; NICHD [T32HD040127]; UNC
Neurodevelopmental Disorders Research Center
FX This work was supported by NIH grants R01 DA022317 (A.P.K.) and R01
MH61887, N01 MH80032, and U19 MH82441 (B.L.R.). S.J.C. was supported by
the Korea Research Foundation Grant funded by the Korean Government
(KRF-2007-357-C00071) and the NIDA fellowship (2006-2007). J.A.A. was
supported by fellowship NICHD T32HD040127 and the UNC Neurodevelopmental
Disorders Research Center. We thank Drs. Arsen Gaysin and Rong He for
technical assistance. We thank Barbara Caldarone for reviewing the
article and providing comments.
NR 26
TC 13
Z9 14
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD JUL
PY 2010
VL 5
IS 8
BP 1221
EP 1225
DI 10.1002/cmdc.201000186
PG 5
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 640OQ
UT WOS:000281061300005
PM 20533502
ER
PT J
AU Ferlin, MG
Bortolozzi, R
Brun, P
Castagliuolo, I
Hamel, E
Basso, G
Viola, G
AF Ferlin, Maria Grazia
Bortolozzi, Roberta
Brun, Paola
Castagliuolo, Ignazio
Hamel, Ernest
Basso, Giuseppe
Viola, Giampietro
TI Synthesis and in vitro Evaluation of 3H-Pyrrolo[3,2-f]quinolin-9-one
Derivatives That Show Potent and Selective Anti-leukemic Activity
SO CHEMMEDCHEM
LA English
DT Article
DE anticancer agents; antiproliferative activity; apoptosis;
pyrroloquinolinones; tubulin
ID CELL-DEATH; APOPTOSIS; BCL-2; PHOSPHATIDYLSERINE; MITOCHONDRIA;
GENERATION; CASPASES; TUBULIN; UPDATE; AGENTS
AB A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI(50) values in the nanomolar range. The active compounds strongly blocked tubulin assembly and colchicine binding to tubulin. Their activities were equal to or greater than that of the reference compound combretastatin A-4. Flow cytometry studies showed that the two most active compounds arrested Jurkat cells in the G(2)/M cell-cycle phase in a concentration-dependent manner. This effect was associated with apoptosis, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and cleavage of the enzyme poly(ADP-ribose) polymerase.
C1 [Ferlin, Maria Grazia] Univ Padua, Dept Pharmaceut Sci, Fac Pharm, I-35131 Padua, Italy.
[Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Dept Pediat, Lab Oncohematol, I-35131 Padua, Italy.
[Brun, Paola; Castagliuolo, Ignazio] Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35131 Padua, Italy.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Ferlin, MG (reprint author), Univ Padua, Dept Pharmaceut Sci, Fac Pharm, Via Marzolo 5, I-35131 Padua, Italy.
EM mariagrazia.ferlin@unipd.it
RI Bortolozzi, Roberta/D-4950-2015; CASTAGLIUOLO, IGNAZIO/K-9963-2016;
Viola, Giampietro/I-4095-2012
OI Bortolozzi, Roberta/0000-0002-3357-4815; CASTAGLIUOLO,
IGNAZIO/0000-0001-9888-7030; BASSO, GIUSEPPE/0000-0002-2634-9302; Viola,
Giampietro/0000-0001-9329-165X
FU Italian Ministry of Education, University and Research (MIUR)
FX This work was supported by grants from the Italian Ministry of
Education, University and Research (MIUR).
NR 26
TC 14
Z9 14
U1 0
U2 2
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD JUL
PY 2010
VL 5
IS 8
BP 1373
EP 1385
DI 10.1002/cmdc.201000180
PG 13
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 640OQ
UT WOS:000281061300022
PM 20629070
ER
PT J
AU Gollenberg, AL
Lynch, CD
Jackson, LW
McGuinness, BM
Msall, ME
AF Gollenberg, A. L.
Lynch, C. D.
Jackson, L. W.
McGuinness, B. M.
Msall, M. E.
TI Concurrent validity of the parent-completed Ages and Stages
Questionnaires, 2nd Ed. with the Bayley Scales of Infant Development II
in a low-risk sample
SO CHILD CARE HEALTH AND DEVELOPMENT
LA English
DT Article
DE child development; developmental screening; diagnostic tests;
sensitivity and specificity
ID AUDITORY MILESTONE SCALE; PRETERM INFANTS; FOLLOW-UP; PEDIATRIC
PRACTICE; PREMATURITY; CHILDREN; IMPACT; INDEX
AB Background
This study assessed the concurrent validity of the Ages and Stages Questionnaire (ASQ) compared with Bayley Scales of Infant Development II (BSID II) amongst children aged 24 months.
Methods
Data were collected from 53 infants and mothers who participated in the New York State Angler Cohort Child Development Study. Parents completed the 24-month ASQ to assess communication, personal-social, problem-solving ability, and fine and gross motor control. The BSID II was administered by a clinical psychologist at the 24-month home visit for cognitive and psychomotor assessment. The ASQ was scored using age-specific norms of < 2 SDs below any domain mean to define failure. A BSID II score of < 85 indicated mild or severe delay, while a score of < 70 suggested a severe delay.
Results
Scores on the ASQ communication and personal-social domains were moderately correlated with the BSID II Mental Scale (R = 0.52, P < 0.001; R = 0.45, P < 0.01) and ASQ gross motor with the BSID II Motor Scale (R = 0.46, P < 0.01), whereas ASQ problem-solving and fine motor domains were not significantly correlated with BSID II scores. The ASQ had a sensitivity of 100% and specificity of 87% at 24 months (n = 40) for severely delayed status.
Conclusions
Results suggest the ASQs provide a simple, valid, and cost-effective method for clinicians and field-based researchers to reduce the number of standardized assessments required to identify developmentally delayed infants at age 24 months. Future studies should further assess the validity of the ASQs in larger, more diverse populations of infants.
C1 [Gollenberg, A. L.] NICHHD, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Gollenberg, A. L.; Msall, M. E.] Univ Chicago, Comer Childrens Hosp, Dept Pediat, LaRabida Childrens Hosp, Chicago, IL 60637 USA.
[Gollenberg, A. L.; Msall, M. E.] JP Kennedy Res Ctr Intellectual & Dev Disabil, Chicago, IL USA.
[Lynch, C. D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Jackson, L. W.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[McGuinness, B. M.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Gollenberg, AL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Biostat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20892 USA.
EM gollenba@mail.nih.gov
FU Great Lakes Protection Fund [RM 791-3021]; Agency for Toxic Substances
and Disease Registry [H75/ATH 298328]; Gerber Foundation; Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health
FX This work was supported, in part, by grants from the Great Lakes
Protection Fund (RM 791-3021), the Agency for Toxic Substances and
Disease Registry (H75/ATH 298328), and the Gerber Foundation as well as
intramural funds from the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health.
NR 22
TC 38
Z9 40
U1 0
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0305-1862
J9 CHILD CARE HLTH DEV
JI Child Care Health Dev.
PD JUL
PY 2010
VL 36
IS 4
BP 485
EP 490
DI 10.1111/j.1365-2214.2009.01041.x
PG 6
WC Psychology, Developmental; Pediatrics
SC Psychology; Pediatrics
GA 609GU
UT WOS:000278644800005
PM 20030657
ER
PT J
AU Davis, JK
Thomas, PJ
Thomas, JW
AF Davis, Jamie K.
Thomas, Pamela J.
Thomas, James W.
CA NISC Comparative Sequencing Progra
TI A W-linked palindrome and gene conversion in New World sparrows and
blackbirds
SO CHROMOSOME RESEARCH
LA English
DT Article
DE palindrome; gene conversion; sex chromosome
ID SEVERE HEMOPHILIA-A; MALE-SPECIFIC REGION; FACTOR-VIII GENE;
SEX-CHROMOSOMES; Y-CHROMOSOMES; X-CHROMOSOME; EVOLUTIONARY STRATA;
SEQUENCE ALIGNMENT; DNA-SEQUENCES; GENOMIC DNA
AB A hallmark feature of the male-specific region of the human Y chromosome is the presence of large and near-identical palindromes. These palindromes are maintained in a state of near identity via gene conversion between the arms of the palindrome, and both neutral and selection-based theories have been proposed to explain their enrichment on the human Y and X chromosomes. While those proposed theories would be applicable to sex chromosomes in other species, it has not been established whether near-identical palindromes are a common feature of sex chromosomes in a broader range of taxa, including other tetrapods. Here, we report the genomic sequencing and features of a 279-kb region of the non-recombining portion of the W chromosome spanning the CHD1W locus in a New World sparrow, the white-throated sparrow (Zonotrichia albicollis), and the corresponding region on the Z chromosome. As has been observed for other Y and W chromosomes, we detected a high repetitive element content (51%) and low gene content on the white-throated sparrow W chromosome. In addition, we identified a 22-kb near-identical (> 99%) palindrome on the W chromosome that flanks the 5' end of the CHD1W gene. Signatures of gene conversion were readily detected between the arms of this palindrome, as was the presence of this palindrome in other New World sparrows and blackbirds. Near-identical palindromes are therefore present on the avian W chromosome and may persist due to the same forces proposed for the enrichment of these elements on the human sex chromosomes.
C1 [Davis, Jamie K.; Thomas, James W.] Emory Univ, Dept Human Genet, Sch Med, Atlanta, GA 30322 USA.
[Thomas, Pamela J.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Thomas, Pamela J.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Thomas, JW (reprint author), Emory Univ, Dept Human Genet, Sch Med, Atlanta, GA 30322 USA.
EM jthomas@genetics.emory.edu
FU National Institutes of Health [1R21MH082046]; National Human Genome
Research Institute of the National Institutes of Health
FX The authors thank Judith E. Mank for helpful comments and discussions,
Mario Caceres for comments, Cheryl T. Strauss for technical writing
edits, Donna L. Maney for the dark-eyed junco DNA, Greg K. Tharp for
computer support, the BC Cancer Agency Genome Sciences Centre,
Vancouver, Canada, for generation of the BAC-end sequences, and members
of the NIH Sequencing Center including E.D. Green, R. Blakesley, G.
Bouffard, and J. McDowell. DNA samples (excluding the dark-eyed junco)
were provided by The Burke Museum of Natural History and Culture. J.K.D.
and J.W.T. were supported by a grant from the National Institutes of
Health (1R21MH082046), and the NIH Intramural Sequencing Center was
supported in part by the Intramural Research Program of the National
Human Genome Research Institute of the National Institutes of Health.
NR 52
TC 7
Z9 7
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD JUL
PY 2010
VL 18
IS 5
BP 543
EP 553
DI 10.1007/s10577-010-9134-y
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 628MY
UT WOS:000280125500002
PM 20535633
ER
PT J
AU Ashikaga, H
Leclercq, C
Wang, J
Kass, DA
McVeigh, ER
AF Ashikaga, Hiroshi
Leclercq, Christophe
Wang, Jiangxia
Kass, David A.
McVeigh, Elliot R.
TI Hemodynamic Improvement in Cardiac Resynchronization Does Not Require
Improvement in Left Ventricular Rotation Mechanics Three-Dimensional
Tagged MRI Analysis
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE MRI; tagging; ventricular function; mechanics; torsional deformation
ID DILATED CARDIOMYOPATHY; TORSIONAL DEFORMATION; HEART-FAILURE; PACING
SITE; THERAPY; RELAXATION; DYSSYNCHRONY; TACHYCARDIA; RECOIL; VOLUME
AB Background-Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics.
Methods and Results-In dogs with left bundle branch block and pacing-induced heart failure (n = 7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity.
Conclusions-CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. (Circ Cardiovasc Imaging. 2010; 3: 456-463.)
C1 [Ashikaga, Hiroshi; Kass, David A.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 20287 USA.
[Ashikaga, Hiroshi; McVeigh, Elliot R.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
[Leclercq, Christophe] Univ Rennes, Dept Cardiol, Rennes, France.
[Wang, Jiangxia] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[McVeigh, Elliot R.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
RP Ashikaga, H (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, 600 N Wolfe St,Carnegie 568, Baltimore, MD 20287 USA.
EM hashika1@jhmi.edu
OI Ashikaga, Hiroshi/0000-0003-3689-6892
FU National Heart, Lung, and Blood Institute [P50-HL52307, P01-HL077180,
Z01-HL004609]; French Federation of Cardiology
FX This work was supported by National Heart, Lung, and Blood Institute
grants P50-HL52307 and P01-HL077180 (to D. A. K.) and Z01-HL004609 (to
E. R. M.) and the French Federation of Cardiology (to C. L.).
NR 29
TC 7
Z9 8
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JUL
PY 2010
VL 3
IS 4
BP 456
EP U142
DI 10.1161/CIRCIMAGING.109.906305
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 628UW
UT WOS:000280149200015
PM 20478988
ER
PT J
AU Reed, SD
Whellan, DJ
Li, YH
Friedman, JY
Ellis, SJ
Pina, IL
Settles, SJ
Davidson-Ray, L
Johnson, JL
Cooper, LS
O'Connor, CM
Schulman, KA
AF Reed, Shelby D.
Whellan, David J.
Li, Yanhong
Friedman, Joelle Y.
Ellis, Stephen J.
Pina, Ileana L.
Settles, Sharon J.
Davidson-Ray, Linda
Johnson, Johanna L.
Cooper, Lawton S.
O'Connor, Christopher M.
Schulman, Kevin A.
CA HF-ACTIOn Investigators
TI Economic Evaluation of the HF-ACTION (Heart Failure: A Controlled Trial
Investigating Outcomes of Exercise Training) Randomized Controlled Trial
An Exercise Training Study of Patients With Chronic Heart Failure
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE costs and cost analysis; exercise therapy; heart failure; cost-benefit
analysis
ID VALSARTAN
AB Background-Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) assigned 2331 outpatients with medically stable heart failure to exercise training or usual care. We compared medical resource use and costs incurred by these patients during follow-up.
Methods and Results-Extensive data on medical resource use and hospital bills were collected throughout the trial for estimates of direct medical costs. Intervention costs were estimated using patient-level trial data, administrative records, and published unit costs. Mean follow-up was 2.5 years. There were 2297 hospitalizations in the exercise group and 2332 in the usual care group (P=0.92). The mean number of inpatient days was 13.6 (standard deviation [SD], 27.0) in the exercise group and 15.0 (SD, 31.4) in the usual care group (P=0.23). Other measures of resource use were similar between groups, except for trends indicating that fewer patients in the exercise group underwent high-cost inpatient procedures. Total direct medical costs per participant were an estimated $50 857 (SD, $81 488) in the exercise group and $56 177 (SD, $92 749) in the usual care group (95% confidence interval for the difference, $-12 755 to $1547; P=0.10). The direct cost of exercise training was an estimated $1006 (SD, $337). Patient time costs were an estimated $5018 (SD, $4600).
Conclusions-The cost of exercise training was relatively low for the health care system, but patients incurred significant time costs. In this economic evaluation, there was little systematic benefit in terms of overall medical resource use with this intervention.
C1 [Reed, Shelby D.; Whellan, David J.; Li, Yanhong; Friedman, Joelle Y.; Ellis, Stephen J.; Settles, Sharon J.; Davidson-Ray, Linda; O'Connor, Christopher M.; Schulman, Kevin A.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA.
[Reed, Shelby D.; Whellan, David J.; Johnson, Johanna L.; O'Connor, Christopher M.; Schulman, Kevin A.] Duke Univ, Sch Med, Dept Med, Durham, NC 27715 USA.
[Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA.
[Pina, Ileana L.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA.
[Cooper, Lawton S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Reed, SD (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM shelby.reed@duke.edu
FU National Heart, Lung, and Blood Institute [5U01HL063747, 5U01HL066461,
5U01HL068973, 5U01HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494,
5U01HL064257, 5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491,
5U01HL064264]; National Institute on Aging [R37AG018915, P60AG010484]
FX HF-ACTION was funded by grants 5U01HL063747, 5U01HL066461, 5U01HL068973,
5U01HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494, 5U01HL064257,
5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491, and 5U01HL064264
from the National Heart, Lung, and Blood Institute and grants
R37AG018915 and P60AG010484 from the National Institute on Aging.
NR 19
TC 18
Z9 18
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2010
VL 3
IS 4
BP 374
EP 381
DI 10.1161/CIRCOUTCOMES.109.907287
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 628NC
UT WOS:000280125900007
PM 20551371
ER
PT J
AU Kalogeropoulos, A
Psaty, BM
Vasan, RS
Georgiopoulou, V
Smith, AL
Smith, NL
Kritchevsky, SB
Wilson, PWF
Newman, AB
Harris, TB
Butler, J
AF Kalogeropoulos, Andreas
Psaty, Bruce M.
Vasan, Ramachandran S.
Georgiopoulou, Vasiliki
Smith, Andrew L.
Smith, Nicholas L.
Kritchevsky, Stephen B.
Wilson, Peter W. F.
Newman, Anne B.
Harris, Tamara B.
Butler, Javed
CA Cardiovasc Hlth Study
TI Validation of the Health ABC Heart Failure Model for Incident Heart
Failure Risk Prediction The Cardiovascular Health Study
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; epidemiology; elderly
ID HIGH BLOOD-PRESSURE; CLINICAL CHARACTERISTICS; SCIENTIFIC STATEMENT;
PREVENTION; PREVALENCE; PROGNOSIS; MORTALITY; EPIDEMIOLOGY; ASSOCIATION;
DYSFUNCTION
AB Background-The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.
Methods and Results-Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5%) participants developed heart failure over 5 years versus 364 (6.8%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2% versus 2.8%, 9.0% versus 7.0%, 15.9% versus 13.7%, and 24.6% versus 30.8% for the < 5%, 5% to 10%, 10% to 20%, and > 20% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5% to 10% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.
Conclusions-The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts. (Circ Heart Fail. 2010;3:495-502.)
C1 [Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Andrew L.; Wilson, Peter W. F.; Butler, Javed] Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30322 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Div Gerontol & Geriatr Med, Winston Salem, NC 27109 USA.
[Newman, Anne B.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Butler, J (reprint author), Emory Univ Hosp, Div Cardiol, 1365 Clifton Rd NE,Ste AT430, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Library, Woodruff Health/A-6096-2012; Newman, Anne/C-6408-2013;
Kalogeropoulos, Andreas/A-9494-2009;
OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos,
Andreas/0000-0002-1284-429X; Ramachandran, Vasan/0000-0001-7357-5970;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133,
U01-HL080295]; National Institute of Neurological Disorders and Stroke;
Clinical and Translational Science [UL1-RR025008]
FX The research reported in this article was supported by contract numbers
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC-45133, and grant number U01-HL080295
from the National Heart, Lung, and Blood Institute, with additional
contributions from the National Institute of Neurological Disorders and
Stroke. A full list of the CHS investigators and institutions can be
found at http://www.chs-nhlbi.org/pi.htm. This project also was
partially funded by an Emory University Heart and Vascular Board grant
entitled "Novel Risk Markers and Prognosis Determination in Heart
Failure" and Public Health Service grant UL1-RR025008 from the Clinical
and Translational Science Award program, National Institutes of Health,
National Center for Research Resources.
NR 38
TC 25
Z9 26
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JUL
PY 2010
VL 3
IS 4
BP 495
EP U55
DI 10.1161/CIRCHEARTFAILURE.109.904300
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 628KN
UT WOS:000280118600005
PM 20427700
ER
PT J
AU O'Shea, J
AF O'Shea, J.
TI PLASTICITY OF TH 17 T CELLS: IMPLICATIONS FOR HUMAN DISEASE
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [O'Shea, J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2010
VL 28
IS 4
BP 598
EP 598
PG 1
WC Rheumatology
SC Rheumatology
GA 653JP
UT WOS:000282086800034
ER
PT J
AU Colbert, RA
AF Colbert, R. A.
TI ENTHESITIS-RELATED ARTHRITIS: IS IT JUVENILE SPONDYLOARTHRITIS?
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Colbert, R. A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2010
VL 28
IS 4
BP 605
EP 605
PG 1
WC Rheumatology
SC Rheumatology
GA 653JP
UT WOS:000282086800054
ER
PT J
AU Layh-Schmitt, G
Colbert, RA
AF Layh-Schmitt, G.
Colbert, R. A.
TI EFFECT OF HLA-B27 EXPRESSION ON RANKL AND TNF-ALPHA INDUCED OSTEOCLAST
DEVELOPMENT IN TRANSGENIC RATS
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Layh-Schmitt, G.; Colbert, R. A.] NIAMS, Pediat Translat Res Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2010
VL 28
IS 4
BP 616
EP 616
PG 1
WC Rheumatology
SC Rheumatology
GA 653JP
UT WOS:000282086800088
ER
PT J
AU Gul, A
Kirino, Y
Ustek, D
Ombrello, MJ
Cosan, F
Yang, B
Gadina, M
O'Shea, J
Kastner, DL
Remmers, EF
AF Gul, Ahmet
Kirino, Yohei
Ustek, Duran
Ombrello, Michael J.
Cosan, Fulya
Yang, Barbara
Gadina, Massimo
O'Shea, John
Kastner, Daniel L.
Remmers, Elaine F.
TI GENETIC PREDISPOSITION FOR LOW IL-10 EXPRESSION IS ASSOCIATED WITH
BEHCET'S DISEASE
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Gul, Ahmet; Ustek, Duran; Cosan, Fulya] Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey.
[Kirino, Yohei; Ombrello, Michael J.; Kastner, Daniel L.; Remmers, Elaine F.] NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA.
[Yang, Barbara; Gadina, Massimo] NIAMSD, Translat Immunol Sect, Off Sci & Technol, Bethesda, MD 20892 USA.
[O'Shea, John] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
RI Ustek, Duran/C-3484-2009
OI Ustek, Duran/0000-0002-0060-2859
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2010
VL 28
IS 4
SU 60
BP S130
EP S131
PG 2
WC Rheumatology
SC Rheumatology
GA 663EN
UT WOS:000282865900097
ER
PT J
AU Henderson, C
Pham, H
Joyal, E
Chapelle, D
Hoffman, P
Plass, N
Stone, D
Sen, HN
Yazici, Y
Goldbach-mansky, R
AF Henderson, Cailin
Pham, Hang
Joyal, Elizabeth
Chapelle, Dawn
Hoffman, Patrycja
Plass, Nikki
Stone, Debbie
Sen, Hatice Nida
Yazici, Yusuf
Goldbach-mansky, Raphaela
TI CLINICAL CHARACTERISTICS AND SERUM CYTOKINES IN A US COHORT OF PATIENTS
WITH BEHCET'S DISEASE AT THE NIH
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Henderson, Cailin; Pham, Hang; Joyal, Elizabeth; Chapelle, Dawn; Hoffman, Patrycja; Plass, Nikki; Stone, Debbie; Sen, Hatice Nida; Yazici, Yusuf; Goldbach-mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA.
NEI, NIH, Bethesda, MD 20892 USA.
NYU, New York, NY 10003 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2010
VL 28
IS 4
SU 60
BP S129
EP S129
PG 1
WC Rheumatology
SC Rheumatology
GA 663EN
UT WOS:000282865900092
ER
PT J
AU Khleif, SN
Doroshow, JH
Hait, WN
AF Khleif, Samir N.
Doroshow, James H.
Hait, William N.
CA AACR-FDA-NCI Canc Biomarkers Colla
TI AACR-FDA-NCI Cancer Biomarkers Collaborative Consensus Report: Advancing
the Use of Biomarkers in Cancer Drug Development
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NEGATIVE BREAST-CANCER; GENE-EXPRESSION; VALIDATION; CHALLENGES;
SIGNATURE; ONCOLOGY; WOMEN
AB Recent discoveries in cancer biology have greatly increased our understanding of cancer at the molecular and cellular level, but translating this knowledge into safe and effective therapies for cancer patients has proved to be challenging. There is a growing imperative to modernize the drug development process by incorporating new techniques that can predict the safety and effectiveness of new drugs faster, with more certainty, and at lower cost. Biomarkers are central to accelerating the identification and adoption of new therapies, but currently, many barriers impede their use in drug development and clinical practice. In 2007, the AACR-FDA-NCI Cancer Biomarkers Collaborative stepped into the national effort to bring together disparate stakeholders to clearly delineate these barriers, to develop recommendations for integrating biomarkers into the cancer drug development enterprise, and to set in motion the necessary action plans and collaborations to see the promise of biomarkers come to fruition, efficiently delivering quality cancer care to patients. Clin Cancer Res; 16(13); 3299-318. (C) 2010 AACR.
C1 [Hait, William N.] Johnson & Johnson Family Co, Ortho Biotech Oncol R&D, Raritan, NJ 08869 USA.
[Khleif, Samir N.; Doroshow, James H.] Johnson & Johnson Family Co, NCI, Raritan, NJ 08869 USA.
RP Hait, WN (reprint author), Johnson & Johnson Family Co, Ortho Biotech Oncol R&D, 920 Route 202, Raritan, NJ 08869 USA.
EM WHait@ITS.JNJ.COM
RI Bast, Robert/E-6585-2011
OI Bast, Robert/0000-0003-4621-8462
FU NCI NIH HHS [U01 CA152990]
NR 35
TC 104
Z9 109
U1 0
U2 14
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 JUL 1
PY 2010
VL 16
IS 13
BP 3299
EP 3318
DI 10.1158/1078-0432.CCR-10-0880
PG 20
WC Oncology
SC Oncology
GA 619AR
UT WOS:000279399200001
PM 20501613
ER
PT J
AU Sethi, AA
Sampson, M
Warnick, R
Muniz, N
Vaisman, B
Nordestgaard, BG
Tybjaerg-Hansen, A
Remaley, AT
AF Sethi, Amar A.
Sampson, Maureen
Warnick, Russell
Muniz, Nehemias
Vaisman, Boris
Nordestgaard, Borge G.
Tybjaerg-Hansen, Anne
Remaley, Alan T.
TI High Pre-beta(1) HDL Concentrations and Low Lecithin: Cholesterol
Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic
Heart Disease and Independent of HDL-Cholesterol
SO CLINICAL CHEMISTRY
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; SANDWICH
ENZYME-IMMUNOASSAY; INTIMA-MEDIA THICKNESS; APOLIPOPROTEIN-A-I;
CARDIOVASCULAR-DISEASE; PARTICLE-SIZE; PRE-BETA; HUMAN PLASMA;
ASSOCIATION
AB BACKGROUND: We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.
METHODS: Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women >= 735 mg/L; men >= 619 mg/L) or low HDL-C (n = 42; women <= 387 mg/L; men <= 341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-beta(1) HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin: cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay.
RESULTS: Pre-beta(1) HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/ L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) mu mol.L-1.h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) mu mol.L-1.h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) HDL in the high-HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61-0.81) for predicting IHD, which increased to 0.92 (0.87-0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001).
CONCLUSIONS: IHD was associated with high pre-beta(1) HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease. (c) 2010 American Association for Clinical Chemistry
C1 [Sethi, Amar A.; Vaisman, Boris; Remaley, Alan T.] NHLBI, NIH, Lipoprot Metab Sect, Bethesda, MD 20892 USA.
[Sampson, Maureen] Ctr Clin, Dept Lab Med, Bethesda, MD USA.
[Warnick, Russell] Berkeley HeartLab, Burlingame, CA USA.
[Muniz, Nehemias] Quantimetrix, Redondo Beach, CA USA.
[Nordestgaard, Borge G.] Univ Copenhagen, Herlev Hosp, Fac Hlth Sci, Copenhagen Univ Hosp, Copenhagen, Denmark.
[Nordestgaard, Borge G.; Tybjaerg-Hansen, Anne] Univ Copenhagen, Copenhagen City Heart Study, Fac Hlth Sci, Copenhagen Univ Hosp, Copenhagen, Denmark.
[Tybjaerg-Hansen, Anne] Univ Copenhagen, Rigshosp, Fac Hlth Sci, Copenhagen Univ Hosp, DK-2100 Copenhagen, Denmark.
RP Sethi, AA (reprint author), Pacific Biomarkers, 220 W Harrison St, Seattle, WA 98119 USA.
EM amars@pacbio.com
FU Danish Agency for Science, Technology and Innovation and National Heart,
Lung, and Blood Institute (NHLBI), NIH; Danish Heart Foundation;
European Union [037631]
FX A.A. Sethi, Danish Agency for Science, Technology and Innovation and
National Heart, Lung, and Blood Institute (NHLBI), NIH; M. Sampson,
NHLBI, NIH; B. Vaisman, NHLBI, NIH; A.T. Remaley, NHLBI, NIH; A.
Tybjarg-Hansen, Danish Heart Foundation and a Specific Targeted Research
Project grant from the European Union, Sixth Framework Program Priority
(FP-2005-LIFESCIHEALTH-6) contract 037631; B.G. Nordestgaard, Danish
Heart Foundation.
NR 42
TC 42
Z9 46
U1 0
U2 0
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2010
VL 56
IS 7
BP 1128
EP 1137
DI 10.1373/clinchem.2009.139931
PG 10
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 617DA
UT WOS:000279259800017
PM 20511449
ER
PT J
AU Stenholm, S
Koster, A
Alley, DE
Visser, M
Maggio, M
Harris, TB
Egan, JM
Bandinelli, S
Guralnik, JM
Ferrucci, L
AF Stenholm, Sari
Koster, Annemarie
Alley, Dawn E.
Visser, Marjolein
Maggio, Marcello
Harris, Tamara B.
Egan, Josephine M.
Bandinelli, Stefania
Guralnik, Jack M.
Ferrucci, Luigi
TI Adipocytokines and the metabolic syndrome among older persons with and
without obesity: the InCHIANTI study
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID HOMEOSTASIS MODEL ASSESSMENT; INSULIN-RESISTANCE SYNDROME;
BODY-COMPOSITION; NORMAL-WEIGHT; SYSTEMIC INFLAMMATION; PLASMA
ADIPONECTIN; PHYSICAL-ACTIVITY; FAT ACCUMULATION; ADIPOKINE LEVELS;
VISCERAL FAT
AB Objectives Adipose tissue-derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non-obese persons.
Design Cross-sectional population-based InCHIANTI study.
Subjects A total of 944 community-dwelling adults aged 65 years and older living in Tuscany, Italy.
Measurements Obesity was defined as body mass index >= 30 kg/m(2) and MetS as >= 3 of the ATP-III criteria. Circulating levels of C-reactive protein, interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-18, tumour necrosis factor (TNF)-alpha R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA-IR).
Results The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA-IR, IL-1ra, TNF-alpha R1 and adiponectin (P < 0.05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (P for trend 0.002) and non-obese persons (P for trend 0.001) independent of insulin resistance.
Conclusions Non-obese and obese individuals who develop an intense pro-inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation.
C1 [Stenholm, Sari; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21225 USA.
[Stenholm, Sari] Natl Inst Hlth & Welf, Div Welf & Hlth Policies, Helsinki, Finland.
[Koster, Annemarie; Harris, Tamara B.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, EMGO Inst, VU Univ Med Ctr,Inst Hlth Sci, Amsterdam, Netherlands.
[Maggio, Marcello] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy.
[Egan, Josephine M.] NIA, Clin Invest Lab, Baltimore, MD 21225 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
RP Stenholm, S (reprint author), NIA, Clin Res Branch, Harbor Hosp 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA.
EM stenholmsm@mail.nih.gov
RI Stenholm, Sari/G-6940-2011
FU Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on
Aging [263 MD 9164, 263 MD 821336]; National Institute on Aging,
National Institutes of Health, Baltimore, Maryland; Finnish Academy
[125494]
FX The InCHIANTI Study baseline (1998-2000) was supported as a 'targeted
project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the US National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336) and by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health, Baltimore, Maryland.
This work was also supported by grant from the Finnish Academy (no.
125494 SS). None of the sponsoring institutions interfered with the
collection, analysis, presentation, or interpretation of the data
reported here.
NR 50
TC 26
Z9 29
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD JUL
PY 2010
VL 73
IS 1
BP 55
EP 65
DI 10.1111/j.1365-2265.2009.03742.x
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 612QR
UT WOS:000278917100009
PM 19878507
ER
PT J
AU Porter, BO
Ouedraogo, GL
Hodge, JN
Smith, MA
Pau, A
Roby, G
Kwan, R
Bishop, RJ
Rehm, C
Mican, J
Sereti, I
AF Porter, Brian O.
Ouedraogo, G. Laissa
Hodge, Jessica N.
Smith, Margo A.
Pau, Alice
Roby, Gregg
Kwan, Richard
Bishop, Rachel J.
Rehm, Catherine
Mican, JoAnn
Sereti, Irini
TI D-Dimer and CRP levels are elevated prior to antiretroviral treatment in
patients who develop IRIS
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Immune reconstitution inflammatory syndrome; Immune restoration disease;
Antiretroviral therapy; Unmasking IRIS; Paradoxical IRIS; Biomarker;
D-dimer; C-reactive protein
ID RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNE RESTORATION DISEASE;
RISK-FACTORS; INFECTED PATIENTS; CRYPTOCOCCAL MENINGITIS;
GRAVES-DISEASE; SOUTH-AFRICA; HIV PATIENTS; THERAPY; TUBERCULOSIS
AB Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naive patients with baseline CD4 T cell counts <= 100 cells/mu L who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. D-Dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann Whitney and Fishers exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking = 8, paradoxical = 7, autoimmune=1. Pre-ART D-dimer and CRP were higher in IRIS cases versus controls (D-dimer: 0.89 mg/L versus 0.66 mg/L, p=0.037; CRP: 0.74 mg/L versus 0.39 mg/L, p=0.022), while D-dimer was higher in unmasking cases at IRIS onset (2.04 mg/L versus 0.36 mg/L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS. Published by Elsevier Inc.
C1 [Porter, Brian O.; Hodge, Jessica N.; Pau, Alice; Roby, Gregg; Rehm, Catherine; Mican, JoAnn; Sereti, Irini] Natl Inst Allergy & Infect Dis NIAD, NIH, Bethesda, MD USA.
[Ouedraogo, G. Laissa] NCI, SAIC Frederick Inc, Clin Monitoring Res Program, Frederick, MD 21702 USA.
[Bishop, Rachel J.] NEI, NIH, Bethesda, MD USA.
[Smith, Margo A.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Kwan, Richard] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIH, Ctr Clin, Bldg 10,Room 11B07A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; Clinical Center
of the National Institutes of Health in Bethesda, Maryland; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX We thank Rebecca DerSimonian for performing HLA genotypic comparative
analyses, Khanh Nghiem and Mary Vailati for coordinating plasma analyses
through the NIH Department of Laboratory Medicine, as well as the staff
and patients of Outpatient Clinic 8 at the NIH Clinical Center.; This
work was supported by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases and the Clinical Center of
the National Institutes of Health in Bethesda, Maryland. Additionally,
this project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
These data were presented in part at the 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town,
South Africa, on July 19-22, 2009.
NR 31
TC 31
Z9 33
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUL
PY 2010
VL 136
IS 1
BP 42
EP 50
DI 10.1016/j.clim.2010.02.010
PG 9
WC Immunology
SC Immunology
GA 613CP
UT WOS:000278954300005
PM 20227921
ER
PT J
AU Lantos, PM
Charini, WA
Medoff, G
Moro, MH
Mushatt, DM
Parsonnet, J
Sanders, JW
Baker, CJ
AF Lantos, Paul M.
Charini, William A.
Medoff, Gerald
Moro, Manuel H.
Mushatt, David M.
Parsonnet, Jeffrey
Sanders, John W.
Baker, Carol J.
TI Final Report of the Lyme Disease Review Panel of the Infectious Diseases
Society of America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID ANTIBIOTIC-TREATMENT; GUIDELINES; DIAGNOSIS; THERAPY; TRIAL
AB In April 2008, the Infectious Diseases Society of America (IDSA) entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. This agreement ended the Attorney General's investigation into the process by which the guidelines were developed. The IDSA agreed to convene an independent panel to conduct a one-time review of the guidelines. The Review Panel members, vetted by an ombudsman for potential conflicts of interest, reviewed the entirety of the 2006 guidelines, with particular attention to the recommendations devoted to post-Lyme disease syndromes. After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.
C1 [Lantos, Paul M.] Duke Univ, Med Ctr, Durham, NC USA.
[Charini, William A.] Lawrence Gen Hosp, Lawrence, MA USA.
[Medoff, Gerald] Washington Univ, Sch Med, St Louis, MO USA.
[Moro, Manuel H.] NIH, Bethesda, MD 20892 USA.
[Mushatt, David M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Parsonnet, Jeffrey] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Baker, Carol J.] Baylor Coll Med, Houston, TX 77030 USA.
[Sanders, John W.] USN, Med Res Ctr Detachment, Lima, Peru.
RP Lantos, PM (reprint author), DUMC 100800, Durham, NC 27710 USA.
EM paul.lantos@duke.edu
FU Infectious Diseases Society of America
FX The Infectious Diseases Society of America.
NR 14
TC 42
Z9 43
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2010
VL 51
IS 1
BP 1
EP 5
DI 10.1086/654809
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 605VM
UT WOS:000278375100001
PM 20504239
ER
PT J
AU Kelly, RJ
Gulley, JL
Giaccone, G
AF Kelly, Ronan J.
Gulley, James L.
Giaccone, Giuseppe
TI Targeting the Immune System in Non-Small-Cell Lung Cancer: Bridging the
Gap Between Promising Concept and Therapeutic Reality
SO CLINICAL LUNG CANCER
LA English
DT Review
DE Dendritic cells; Immunomodulation; T lymphocytes; Vaccines
ID 1E10 ANTIIDIOTYPE VACCINE; BLP25 LIPOSOME VACCINE; GROWTH-FACTOR-BETA;
PHASE-I TRIAL; DENDRITIC CELLS; CARCINOEMBRYONIC ANTIGEN; BACTERIAL-DNA;
HUMAN MUC1; T-CELLS; MONOCLONAL-ANTIBODIES
AB Developing effective immunotherapy for lung cancer is a daunting but hugely attractive challenge. Until recently, non-small-cell lung cancer (NSCLC) was thought of as a nonimmunogenic tumor, but there is now evidence highlighting the integral role played by both inflammatory and immunologic responses in lung carcinogenesis. Despite recent encouraging preclinical and phase I/II data, there are a paucity of phase III trials showing a clear clinical benefit for vaccines in lung cancer. There are many difficulties to overcome before the development of a successful therapy. Perhaps a measurable immune response may not translate into a clinically meaningful or radiologic response. Patient,selection may also be a problem for ongoing clinical studies. The majority of trials for lung cancer vaccines are focused on patients with an advanced stage of the disease, however, the ideal candidates may be patients with a lower tumor burden and stage I or II disease Selecting the exact antigens to target is also difficult. It will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors use. This review discusses the most promising active immunotherapy using protein/peptide vaccines, whole cell vaccines, and dendrite cell vaccines and examines current phase I and II clinical trial data on some novel nonspecific immunomodulating agents
C1 [Kelly, Ronan J.; Gulley, James L.; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Giaccone, Giuseppe/E-8297-2017
OI Gulley, James/0000-0002-6569-2912; Giaccone,
Giuseppe/0000-0002-5023-7562
FU Intramural NIH HHS [Z01 BC010666-03]
NR 96
TC 16
Z9 17
U1 0
U2 5
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1525-7304
J9 CLIN LUNG CANCER
JI Clin. Lung Cancer
PD JUL
PY 2010
VL 11
IS 4
BP 228
EP 237
DI 10.3816/CLC.2010.n.029
PG 10
WC Oncology
SC Oncology
GA 620JS
UT WOS:000279496400003
PM 20630824
ER
PT J
AU Shin, HW
Kang, SY
Hallett, M
Sohn, YH
AF Shin, Hae-Won
Kang, Suk Y.
Hallett, Mark
Sohn, Young H.
TI Extended surround inhibition in idiopathic paroxysmal kinesigenic
dyskinesia
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Paroxysmal kinesigenic dyskinesia; TMS; Motor control; Inhibition
ID FOCAL HAND DYSTONIA; INTRACORTICAL INHIBITION; MODULATION; ACTIVATION;
MUSCLE
AB Objective: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent attacks of dyskinesia, in which movement of one body part produces involuntary movements of other body parts. Surround inhibition (SI), a mechanism for suppression of unwanted movements, could be deficient in these patients. To test this idea, we performed a transcranial magnetic stimulation (TMS) study in drug-naive patients with PKD.
Methods: TMS was set to be triggered by self-initiated flexion of the index finger at different intervals. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest. Normalized MEP amplitudes of the patients' self-triggered TMS sessions at different intervals were compared to those of the controls.
Results: During index finger flexion, MEP amplitudes from the little finger muscle were unchanged in both the patients and normal subjects, however, post-movement MEP enhancement observed in the normal subjects was absent in patients with PKD. These results suggest that the functional operation of SI is itself preserved, but that post-movement excitation of surrounding muscles is deficient in PKD.
Conclusions: This finding may represent that the operation of SI is extended to the post-movement period, perhaps as a compensatory mechanism for preventing unwanted movement in surrounding muscles.
Significance: While many types of impaired inhibition have been described previously in PKD, this is the first possible example of increased inhibition. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Shin, Hae-Won; Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Dept Neurol, Coll Med, Seoul 120752, South Korea.
[Shin, Hae-Won; Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea.
[Shin, Hae-Won] Univ Ulsan, Coll Med, Dept Neurol, Parkinson & Alzheimer Ctr,Asan Med Ctr, Seoul, South Korea.
[Kang, Suk Y.] Hallym Univ, Coll Med, Kangnam Sacred Heart Hosp, Dept Neurol, Seoul, South Korea.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Sohn, YH (reprint author), Yonsei Univ, Dept Neurol, Coll Med, 134 Shinchon Dong, Seoul 120752, South Korea.
EM yhsohn62@yuhs.ac
FU Yonsei University
FX This work was supported by the Brain Korea 21 Project for Medical
Science, Yonsei University.
NR 20
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD JUL
PY 2010
VL 121
IS 7
BP 1138
EP 1141
DI 10.1016/j.clinph.2010.02.001
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 603QE
UT WOS:000278222300022
PM 20202900
ER
PT J
AU Atkinson, AJ
Lyster, PM
AF Atkinson, A. J., Jr.
Lyster, P. M.
TI Systems Clinical Pharmacology
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID DRUG DISCOVERY; PHYSIOLOGY; BIOMARKER; BIOLOGY; MODELS
C1 [Atkinson, A. J., Jr.] Northwestern Univ, Dept Mol Pharmacol & Biochem, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lyster, P. M.] NIGMS, Ctr Bioinformat & Computat Biol, NIH, Bethesda, MD USA.
RP Atkinson, AJ (reprint author), Northwestern Univ, Dept Mol Pharmacol & Biochem, Feinberg Sch Med, Chicago, IL 60611 USA.
EM Art_Atkinson@msn.com
NR 20
TC 10
Z9 10
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUL
PY 2010
VL 88
IS 1
BP 3
EP 6
DI 10.1038/clpt.2010.88
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 617IC
UT WOS:000279273200001
PM 20562885
ER
PT J
AU Berg, JM
Rogers, ME
Lyster, PM
AF Berg, J. M.
Rogers, M. E.
Lyster, P. M.
TI Systems Biology and Pharmacology
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
AB Drug action depends not only on the direct consequences of the interaction between the drug and its target but also on other consequences within the complex physiological system that is the human body. The national institute of general medical sciences (NIGMS) has brought together investigators from the emerging field of systems biology with pharmacologists to explore possible avenues for utilizing the concepts of systems biology to explore problems in pharmaceutical action and drug discovery.
C1 [Berg, J. M.; Rogers, M. E.; Lyster, P. M.] NIGMS, Bethesda, MD USA.
RP Berg, JM (reprint author), NIGMS, Bethesda, MD USA.
EM bergj@nigms.nih.gov
OI Berg, Jeremy/0000-0003-3022-0963
NR 3
TC 15
Z9 15
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUL
PY 2010
VL 88
IS 1
BP 17
EP 19
DI 10.1038/clpt.2010.69
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 617IC
UT WOS:000279273200003
PM 20562889
ER
PT J
AU Holland, MG
Schwope, DM
Stoppacher, R
Gillen, S
Huestis, MA
AF Holland, M. G.
Schwope, D. M.
Stoppacher, R.
Gillen, S.
Huestis, M. A.
TI Postmortem Redistribution of delta-9-tetrahydrocannabinol (THC),
11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH)
SO CLINICAL TOXICOLOGY
LA English
DT Meeting Abstract
C1 [Holland, M. G.] SUNY Upstate Med Univ, Syracuse, NY USA.
[Holland, M. G.] Upstate New York Poison Ctr, Syracuse, NY USA.
[Schwope, D. M.; Huestis, M. A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Stoppacher, R.; Gillen, S.] Onondaga Cty Med Examiners Off, Syracuse, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1556-3650
J9 CLIN TOXICOL
JI Clin. Toxicol.
PD JUL
PY 2010
VL 48
IS 6
MA 231
BP 652
EP 652
PG 1
WC Toxicology
SC Toxicology
GA 671HY
UT WOS:000283492900249
ER
PT J
AU Hon, YY
Chamberlain, CE
Kleiner, DE
Ring, MS
Hale, DA
Kirk, AD
Mannon, RB
AF Hon, Yuen Yi
Chamberlain, Christine E.
Kleiner, David E.
Ring, Michael S.
Hale, Douglas A.
Kirk, Allan D.
Mannon, Roslyn B.
TI Evaluation of tacrolimus abbreviated area-under-the-curve monitoring in
renal transplant patients who are potientially at risk for adverse
events
SO CLINICAL TRANSPLANTATION
LA English
DT Article
DE abbreviated AUC; biopsy-proven acute rejection; tacrolimus
immunosuppression; therapeutic drug monitoring; trough concentration
ID KIDNEY-TRANSPLANTATION; MYCOPHENOLIC-ACID; COMBINATION THERAPY; ACUTE
REJECTION; TROUGH LEVELS; RECIPIENTS; PHARMACOKINETICS;
IMMUNOSUPPRESSION; CYCLOSPORINE; SIROLIMUS
AB In a cohort of 32 renal transplant patients who are potentially at risk for adverse events, we compared tacrolimus (TAC) abbreviated AUC values calculated by a method developed in Asians (AUCw) with those derived for Caucasians (AUCa). The relationships between TAC trough (C0), abbreviated AUC, and biopsy results were also assessed. Forty-eight AUCs and 15 associated biopsies were evaluated. For AUCs obtained only from Caucasian patients, median AUCw value was lower than that of AUCa (104 vs. 115 ng x h/mL, n = 29, p < 0.0001). AUCs obtained from the two methods for all patients correlated with C0 (r(s) > 0.72, n = 48, p < 0.0001). Median AUCw (72.9 vs. 174 ng x h/mL, p = 0.043) and AUCa (81.0 vs. 203 ng x h/mL, p = 0.043) were lower in patients experiencing biopsy-proven acute rejection (AR) than those with normal histology. C0 tended to be lower in biopsies showing AR > 6 months post-transplant (5.80 vs. 11.0 ng/mL, p = 0.110). Thus, lower abbreviated AUCs were obtained for Caucasians using a method developed in Asians. C0 correlated well with abbreviated AUCs. Lower C0 and AUC appeared to be associated with biopsy-proven AR > 6 months post-transplant. Further prospective evaluation of TAC AUC and C0 monitoring in a larger cohort of patients is warranted.
C1 [Ring, Michael S.; Hale, Douglas A.; Kirk, Allan D.; Mannon, Roslyn B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD USA.
[Hon, Yuen Yi; Chamberlain, Christine E.] NIDDK, Dept Pharm, Ctr Clin, NIH, Bethesda, MD USA.
[Kleiner, David E.] NIDDK, Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD USA.
RP Hon, YY (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N-257,MSC 1196,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chon@cc.nih.gov
RI Kirk, Allan/B-6905-2012;
OI Kleiner, David/0000-0003-3442-4453
FU NIH, Clinical Center Pharmacy Department,; National Institute of
Diabetes and Digestive and Kidney Diseases Transplantation Branch, and
National Cancer Institute Laboratory of Pathology
FX This research was supported by the Intramural Research Program of the
NIH, Clinical Center Pharmacy Department, National Institute of Diabetes
and Digestive and Kidney Diseases Transplantation Branch, and National
Cancer Institute Laboratory of Pathology. There was no commercial
sponsorship.
NR 30
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0902-0063
J9 CLIN TRANSPLANT
JI Clin. Transplant.
PD JUL-AUG
PY 2010
VL 24
IS 4
BP 557
EP 563
DI 10.1111/j.1399-0012.2009.01143.x
PG 7
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 639RI
UT WOS:000280991700024
PM 19925470
ER
PT J
AU Park, Y
Killen, M
AF Park, Yoonjung
Killen, Melanie
TI When is peer rejection justifiable? Children's understanding across two
cultures
SO COGNITIVE DEVELOPMENT
LA English
DT Article
DE Social judgment; Peer interaction; Cultural comparison; Social-cognitive
domain theory
ID SOCIAL IDENTITY; GROUP EXCLUSION; VICTIMIZATION; INCLUSION; BEHAVIOR;
VIOLENCE; KINDERGARTEN; STEREOTYPES; ADOLESCENTS; ADJUSTMENT
AB This study investigated how Korean (N = 397) and U.S. (N = 333) children and adolescents (10 and 13 years of age) evaluated personality (aggression, shyness) and group (gender, nationality) characteristics as a basis for peer rejection in three contexts (friendship rejection, group exclusion, victimization). Overall, peer rejection based on group membership was viewed as more unfair than peer rejection based on personality traits. Children viewed friendship rejection as more legitimate than group exclusion or victimization and used more personal choice reasoning for friendship rejection than for rejection in any other context. Although there were a few cultural differences, overall, the findings provided support for the cultural generalizability of social reasoning about peer rejection. Published by Elsevier Inc.
C1 [Killen, Melanie] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Park, Y (reprint author), NICHD, Sect Child & Family Res, NIH, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
EM parkyoon@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [T32 HD007542]
NR 58
TC 16
Z9 16
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-2014
J9 COGNITIVE DEV
JI Cogn. Dev.
PD JUL-SEP
PY 2010
VL 25
IS 3
BP 290
EP 301
DI 10.1016/j.cogdev.2009.10.004
PG 12
WC Psychology, Developmental; Psychology, Experimental
SC Psychology
GA 653GZ
UT WOS:000282078700008
PM 21076660
ER
PT J
AU Andreotti, AH
Schwartzberg, PL
Joseph, RE
Berg, LJ
AF Andreotti, Amy H.
Schwartzberg, Pamela L.
Joseph, Raji E.
Berg, Leslie J.
TI T-Cell Signaling Regulated by the Tec Family Kinase, Itk
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID BRUTONS TYROSINE KINASE; PLECKSTRIN HOMOLOGY DOMAIN; X-LINKED
AGAMMAGLOBULINEMIA; INTERMOLECULAR SELF-ASSOCIATION; SH2 DOMAIN;
POSITIVE SELECTION; SRC-FAMILY; C-SRC; PHOSPHATIDYLINOSITOL 3-KINASE;
INTERLEUKIN-17A AND-17F
AB The Tec family tyrosine kinases regulate lymphocyte development, activation, and differentiation. In T cells, the predominant Tec kinase is Itk, which functions downstream of the T-cell receptor to regulate phospholipase C-gamma. This review highlights recent advances in our understanding of Itk kinase structure and enzymatic regulation, focusing on Itk protein domain interactions and mechanisms of substrate recognition. We also discuss the role of Itk in the development of conventional versus innate T-cell lineages, including both alpha beta and gamma delta T-cell subsets. Finally, we describe the complex role of Itk signaling in effector T-cell differentiation and the regulation of cytokine gene expression. Together, these data implicate Itk as an important modulator of T-cell signaling and function.
C1 [Andreotti, Amy H.; Joseph, Raji E.] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.
[Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20814 USA.
[Berg, Leslie J.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
RP Andreotti, AH (reprint author), Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.
EM amyand@iastate.edu
FU National Institutes of Health [AI37584, AI46564, AI043957, AI075150];
NHGRI/NIH
FX This work was supported by grants from the National Institutes of Health
(AI37584 and AI46564 to LJB and AI043957 and AI075150 to AHA) and by
intramural funds from the NHGRI/NIH (PLS). We thank Julia Fekecs for
assistance with graphic illustrations.
NR 156
TC 53
Z9 53
U1 0
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD JUL
PY 2010
VL 2
IS 7
AR a002287
DI 10.1101/cshperspect.a002287
PG 21
WC Cell Biology
SC Cell Biology
GA 625GM
UT WOS:000279883100010
PM 20519342
ER
PT J
AU Liu, WL
Sohn, HW
Tolar, P
Pierce, SK
AF Liu, Wanli
Sohn, Hae Won
Tolar, Pavel
Pierce, Susan K.
TI It's All About Change: The Antigen-driven Initiation of B-Cell Receptor
Signaling
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID RESONANCE ENERGY-TRANSFER; RESPONSES IN-VIVO; SYNAPSE FORMATION; CLONAL
SELECTION; LIVING CELLS; LIPID RAFTS; LYMPH-NODE; SUBCAPSULAR SINUS;
IMMUNE-RESPONSE; PLASMA-CELL
AB B-cell responses are initiated by the binding of foreign antigens to the clonally distributed B-cell receptors (BCRs) resulting in the triggering of signaling cascades that activate a variety of genes associated with B-cell activation. Although we now understand the molecular nature of the signaling pathways in considerable detail what remains only poorly understood are the mechanisms by which the information that antigen has bound to the BCR ectodomain is transduced across the B-cell membrane to the BCR cytoplasmic domains to trigger signaling. To a large part this gap in knowledge is because of the paucity of techniques to temporally and spatially resolve changes in the behavior of the BCR that occur within several seconds of antigen binding. With the advent of new live-cell imaging technologies we are gaining our first clear views of the events that lead up to the triggering of BCR signaling cascades. These events may provide potential new targets for therapeutic intervention in disease involving hyper or chronic activation of B cells.
C1 [Liu, Wanli; Sohn, Hae Won; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Tolar, Pavel] Natl Inst Med Res, London NW7 1AA, England.
RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM spierce@niaid.nih.gov
RI liu, wanli/H-5690-2011
OI liu, wanli/0000-0003-2624-6802
FU Intramural NIH HHS [Z01 AI000898-08]; Medical Research Council
[MC_U117597138]
NR 54
TC 12
Z9 12
U1 1
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD JUL
PY 2010
VL 2
IS 7
AR a002295
DI 10.1101/cshperspect.a002295
PG 12
WC Cell Biology
SC Cell Biology
GA 625GM
UT WOS:000279883100011
PM 20591989
ER
PT J
AU Ma, Y
Kiesewetter, DO
Lang, LX
Gu, DY
Chen, XY
AF Ma, Ying
Kiesewetter, Dale O.
Lang, Lixin
Gu, Dongyu
Chen, Xiaoyuan
TI Applications of LC-MS in PET Radioligand Development and Metabolic
Elucidation
SO CURRENT DRUG METABOLISM
LA English
DT Review
DE Positron emission tomography (PET); Radiopharmaceutical; LC/MS/MS;
Metabolite
ID TANDEM MASS-SPECTROMETRY; 5-HT1A RECEPTOR RADIOLIGAND; HUMAN PLASMA;
IN-VIVO; RAT HEPATOCYTES; RADIOACTIVE METABOLITES; IDENTITY
CONFIRMATION; MUSCARINIC RECEPTOR; BRAIN UPTAKE; DOPAMINE D2
AB Positron emission tomography (PET) is a very sensitive molecular imaging technique that when employed with an appropriate radioligand has the ability to quantititate physiological processes in a non-invasive manner. Since the imaging technique detects all radioactive emissions in the field of view, the presence and biological activity of radiolabeled metabolites must be determined for each radioligand in order to validate the utility of the radiotracer for measuring the desired physiological process. Thus, the identification of metabolic profiles of radiolabeled compounds is an important aspect of design, development, and validation of new radiopharmaceuticals and their applications in drug development and molecular imaging. Metabolite identification for different chemical classes of radiopharmaceuticals allows rational design to minimize the formation and accumulation of metabolites in the target tissue, either through enhanced excretion or minimized metabolism. This review will discuss methods for identifying and quantitating metabolites during the pre-clinical development of radiopharmaceuticals with special emphasis on the application of LC/MS.
C1 [Ma, Ying; Kiesewetter, Dale O.; Lang, Lixin; Gu, Dongyu; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA.
EM dk7k@nih.gov; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH), U.S.A
FX Financial support for this work was provided by the intramural program
of the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), a component of the National Institutes of Health (NIH), U.S.A.
NR 51
TC 10
Z9 10
U1 0
U2 9
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2002
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PD JUL
PY 2010
VL 11
IS 6
BP 483
EP 493
PG 11
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 628OO
UT WOS:000280130100001
PM 20540692
ER
PT J
AU Nayak, L
Iwamoto, FM
AF Nayak, Lakshmi
Iwamoto, Fabio M.
TI Primary Brain Tumors in the Elderly
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Elderly; Glioma; Glioblastoma; Oligodendroglioma; Astrocytoma; Primary
central nervous system lymphoma; Meningioma; Primary brain tumor;
Chemotherapy; Radiotherapy
ID NERVOUS-SYSTEM LYMPHOMA; PRIMARY CNS LYMPHOMA; RADIOTHERAPY PLUS
CONCOMITANT; GLIOBLASTOMA-MULTIFORME; RADIATION-THERAPY; MALIGNANT
GLIOMAS; PHASE-II; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE;
NATURAL-HISTORY
AB The incidence of primary brain tumors is highest in elderly patients, and advanced age often is a negative prognostic factor. Nevertheless, large randomized studies in this population are scarce. Elderly patients with primary brain tumors also present unique challenges, such as the presence of multiple comorbidities and polypharmacy, decreased tolerance to chemotherapy, and an increased risk for radiation-induced neurotoxicity. This review gives an overview of the treatment options for older patients with glioblastoma and other gliomas, primary central nervous system lymphomas (PCNSLs), and meningiomas. Selected elderly glioblastoma patients with good performance status may benefit from aggressive treatment with surgical resection, radiotherapy, and possibly chemotherapy. For older patients with PCNSLs, high-dose methotrexate-based chemotherapy should be the mainstay option; whole-brain radiation therapy should be avoided in chemosensitive tumors because of the high risk of irreversible and progressive neurotoxicity. Meningiomas often may be followed up in elderly patients, as they usually are asymptomatic and have a slow growth rate. Treatment for elderly patients with primary brain tumors should be individualized, and age alone should not preclude the use of more aggressive treatments.
C1 [Iwamoto, Fabio M.] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
[Nayak, Lakshmi] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
RP Iwamoto, FM (reprint author), NINDS, Neurooncol Branch, NCI, NIH, 9030 Old Georgetown Rd,Room 221, Bethesda, MD 20892 USA.
EM nayakl@mskcc.org; iwamotofm@mail.nih.gov
NR 49
TC 2
Z9 2
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
EI 1534-6293
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD JUL
PY 2010
VL 10
IS 4
BP 252
EP 258
DI 10.1007/s11910-010-0110-x
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 602AZ
UT WOS:000278111800001
PM 20461477
ER
PT J
AU Niswander, LM
Kim, SY
AF Niswander, Lisa M.
Kim, Su Young
TI Stratifying Osteosarcoma: Minimizing and Maximizing Therapy
SO CURRENT ONCOLOGY REPORTS
LA English
DT Article
DE Osteosarcoma; Risk stratification; Targeted therapy
ID GROWTH-FACTOR RECEPTOR; OSTEOGENIC-SARCOMA; PEDIATRIC-PATIENTS; SOLID
TUMORS; CANCER; INTEGRIN; OPPORTUNITIES; ANGIOGENESIS; CHEMOTHERAPY;
METASTASIS
AB Patients who are newly diagnosed with osteosarcoma face a daunting year of medical and surgical therapy, often filled with hospitalizations and changes in lifestyle. Fortunately, the majority of patients endure this struggle to become long-term survivors. However, follow-up studies of cancer survivors are revealing the sequelae of this curative therapy. Just as disturbingly, there remains a large subset of patients for whom conventional therapy is inadequate and who succumb to disease. In this review, we propose that therapeutic strategies for osteosarcoma patients must rely on stratification of patients into risk categories, in order to minimize therapy for some, while expanding treatment for others. We then focus on two molecular targets for the treatment of patients with high-risk osteosarcoma.
C1 [Niswander, Lisa M.; Kim, Su Young] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Kim, SY (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC 1w-3750, Bethesda, MD 20892 USA.
EM kimsuyou@mail.nih.gov
NR 36
TC 10
Z9 13
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3790
J9 CURR ONCOL REP
JI Curr. Oncol. Rep.
PD JUL
PY 2010
VL 12
IS 4
BP 266
EP 270
DI 10.1007/s11912-010-0106-3
PG 5
WC Oncology
SC Oncology
GA 723IO
UT WOS:000287500300008
PM 20473649
ER
PT J
AU Einhorn, PT
Davis, BR
Wright, JT
Rahman, M
Whelton, PK
Pressel, SL
AF Einhorn, Paula T.
Davis, Barry R.
Wright, Jackson T., Jr.
Rahman, Mahboob
Whelton, Paul K.
Pressel, Sara L.
CA ALLHAT Cooperative Res Grp
TI ALLHAT: still providing correct answers after 7 years
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
DE ACE inhibitors; alpha blockers; antihypertensive therapy; calcium
channel blockers; diuretics; thiazides
ID HEART-ATTACK TRIAL; LIPID-LOWERING TREATMENT;
CONVERTING-ENZYME-INHIBITOR; JOINT NATIONAL COMMITTEE; HIGH
BLOOD-PRESSURE; PROSPECTIVELY-DESIGNED OVERVIEWS; VENTRICULAR EJECTION
FRACTIONS; MAJOR CARDIOVASCULAR EVENTS; RANDOMIZED CONTROLLED-TRIAL;
GLOMERULAR-FILTRATION-RATE
AB Purpose of review
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is re-evaluated considering information from recent subgroup and exploratory analyses, other new clinical trials, and meta-analyses. The ALLHAT analyses specifically emphasize heart failure findings, results in Black participants and those with chronic kidney disease, selection and doses of thiazide and similar diuretics, and the association of antihypertensive drug use with new-onset diabetes and its cardiovascular consequences.
Recent findings
The initial ALLHAT conclusion, that thiazide diuretics are superior to angiotensin-converting enzyme inhibitors (ACEIs), calcium antagonists (CCBs) and alpha-blockers in preventing one or more major clinical outcomes, including heart failure and stroke, and unsurpassed in significantly preventing any cardiovascular or renal outcome, has been further validated for patients with diabetes, renal disease, and/or metabolic syndrome. The evidence is even more compelling for Black patients. New-onset diabetes associated with thiazides did not increase cardiovascular outcomes. The diuretic was superior to all in preventing heart failure with preserved left-ventricular ejection fraction (LVEF) and similar to the ACEI in preventing heart failure with impaired LVEF. It was also unsurpassed in preventing atrial fibrillation.
Summary
The totality of evidence re-affirms the initial ALLHAT conclusion that thiazide and similar diuretics (at evidence-based doses) are the preferred first-step therapy in most patients with hypertension.
C1 [Davis, Barry R.; Pressel, Sara L.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA.
[Wright, Jackson T., Jr.; Rahman, Mahboob] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Whelton, Paul K.] Loyola Univ Med Ctr & Hlth Syst, Maywood, IL USA.
RP Pressel, SL (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA.
EM Sara.L.Pressel@uth.tmc.edu
FU NHLBI NIH HHS [N01-HC-35130]
NR 68
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
EI 1531-7080
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD JUL
PY 2010
VL 25
IS 4
BP 355
EP 365
DI 10.1097/HCO.0b013e32833a8828
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 608FY
UT WOS:000278569800011
PM 20520537
ER
PT J
AU Strober, W
Zhang, FP
Kitani, A
Fuss, I
Fichtner-Feigl, S
AF Strober, Warren
Zhang, Fuping
Kitani, Atsushi
Fuss, Ivan
Fichtner-Feigl, Stefan
TI Proinflammatory cytokines underlying the inflammation of Crohn's disease
SO CURRENT OPINION IN GASTROENTEROLOGY
LA English
DT Article
DE Crohn's disease; interferon-gamma; interleukin-12; interleukin-17;
interleukin-22; interleukin-23; T helper cell 1 response; T helper cell
17 response; tumor necrosis factor-like ligand 1A
ID MEDIATED INTESTINAL INFLAMMATION; T-CELLS; EXPERIMENTAL COLITIS;
BOWEL-DISEASE; MONOCLONAL-ANTIBODY; ULCERATIVE-COLITIS; TH17 CELLS;
TGF-BETA; RESPONSES; IL-23
AB Purpose of review
To encapsulate our current understanding of the proinflammatory cytokines responsible for the inflammation underlying Crohn's disease and the prospect of using this information to devise therapy for this condition based on inhibition of these cytokines.
Recent findings
Current research is shedding new light on the role of both T helper cell (Th)1 and Th17 responses in the pathogenesis of Crohn's disease. Initial studies conducted a decade ago highlighted the view that Crohn's disease inflammation is caused by an interleukin-12-driven Th1 response, which resulted in the generation of interferon-gamma, which then served as the main inflammatory mediator. In recent years, however, this view has been largely eclipsed by studies, conducted mainly in murine models, showing that a Th17 response is the main cause of Crohn's disease inflammation through the production of interleukin-17. Now, a somewhat more balanced view is emerging, which holds that interferon-gamma is still a major proinflammatory cytokine in Crohn's disease, although it may arise from both the Th1 and Th17-mediated responses at different phases of the inflammatory process.
Summary
The new findings continue to support the idea that anti-interleukin-12p40, an antibody that inhibits both the Th1 and Th17 response, is logically the most potent anticytokine for the treatment of Crohn's disease.
C1 [Strober, Warren; Zhang, Fuping; Kitani, Atsushi; Fuss, Ivan] NIAID, Mucosal Immun Sect, Lab Host Def, Bethesda, MD 20892 USA.
[Fichtner-Feigl, Stefan] Univ Regensberg, Dept Surg, Regensburg, Germany.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Lab Host Def, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM Wstrober@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000872-09, Z99 AI999999]
NR 35
TC 46
Z9 49
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0267-1379
J9 CURR OPIN GASTROEN
JI Curr. Opin. Gastroenterol.
PD JUL
PY 2010
VL 26
IS 4
BP 310
EP 317
DI 10.1097/MOG.0b013e328339d099
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 613YO
UT WOS:000279021500003
PM 20473158
ER
PT J
AU Goldin, LR
Slager, SL
Caporaso, NE
AF Goldin, Lynn R.
Slager, Susan L.
Caporaso, Neil E.
TI Familial chronic lymphocytic leukemia
SO CURRENT OPINION IN HEMATOLOGY
LA English
DT Article
DE chronic lymphocytic leukemia; familial; germline genes; monoclonal
B-cell lymphocytosis
ID B-CELL LYMPHOCYTOSIS; POPULATION-BASED SAMPLES; NON-HODGKIN-LYMPHOMA;
LYMPHOPROLIFERATIVE DISORDERS; 1ST-DEGREE RELATIVES; SUSCEPTIBILITY
GENES; MUTATION STATUS; RISK; CLL; AGGREGATION
AB Purpose of review
Families with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature and strong familial aggregation has been seen in population studies. However, predisposing germline mutations have not been identified. We will discuss the spectrum of conditions associated with CLL in families and the advances in identifying the underlying susceptibility genes.
Recent findings
Familial CLL does not appear to differ substantially from sporadic CLL in terms of prognostic markers and clinical outcome, although it may be associated with more indolent disease. The precursor condition, monoclonal B-cell lymphocytosis, also aggregates in CLL families. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for susceptibility loci but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated several genes as being important in CLL but more studies are needed. Results from whole-genome association studies are promising.
Summary
The ability to conduct large-scale genomic studies in unrelated CLL patients and in high-risk CLL families will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate causal pathways.
C1 [Goldin, Lynn R.; Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Slager, Susan L.] Mayo Clin, Rochester, MN USA.
RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7008,MSC 7236, Bethesda, MD 20892 USA.
EM goldinl@mail.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH),
Bethesda, Maryland, USA; NIH [CA118444]
FX This article is based upon work supported by the Intramural Program of
the National Cancer Institute, National Institutes of Health (NIH),
Bethesda, Maryland, USA, and by NIH grant #CA118444.
NR 56
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1065-6251
J9 CURR OPIN HEMATOL
JI Curr. Opin. Hematol.
PD JUL
PY 2010
VL 17
IS 4
BP 350
EP 355
DI 10.1097/MOH.0b013e328338cd99
PG 6
WC Hematology
SC Hematology
GA 613ZJ
UT WOS:000279023700013
PM 20389242
ER
PT J
AU Keele, BF
AF Keele, Brandon F.
TI Identifying and characterizing recently transmitted viruses
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE acute infection; HIV; simian immunodeficiency virus; transmitted virus;
viral evolution
ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; HIV-1 INFECTION;
HETEROSEXUAL TRANSMISSION; SELECTIVE TRANSMISSION; DISEASE PROGRESSION;
TYPE-1 INFECTION; RHESUS MACAQUES; IMMUNE ESCAPE; SIV INFECTION
AB Purpose of review
Improvements in sequencing approaches and robust mathematical modeling have dramatically increased information on viral genetics during acute infection with HIV and simian immunodeficiency virus, providing unprecedented insight into viral transmission and viral/immune interactions.
Recent findings
Overall viral genetic diversity is reduced significantly during mucosal transmission. Remarkably, in the vast majority of sexual transmissions, this diversity is reduced to a single viral variant that establishes the initial productive clinical infection. By identifying and enumerating transmitted/founder viruses, researchers can begin to define the characteristics that are necessary and sufficient for successful viral replication within a new host.
Summary
Acute HIV infection is a critical window of opportunity for vaccine and therapeutic intervention. New sequencing technologies and mathematical modeling of transmission and early evolution have provided a clearer understanding of the number of founder viruses that establish infection, the rapid generation of diversity in these viruses and the subsequent evasion of host immunity. The information gained by identifying transmitted viruses, monitoring the initial host responses to these viruses and then identifying mechanisms of viral escape could provide better strategies for vaccine development, preexposure prophylaxis, microbicides, or other therapeutic interventions.
C1 NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21701 USA.
RP Keele, BF (reprint author), NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Rm 408,Bldg 535, Frederick, MD 21701 USA.
EM keelebf@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN266200400088C]
FX The author is grateful to Jacob Estes and Jeff Lifson for many valuable
suggestions to this manuscript. The author was supported with federal
funds from the National Cancer Institute, National Institutes of Health
under contract HHSN266200400088C.
NR 65
TC 30
Z9 33
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD JUL
PY 2010
VL 5
IS 4
BP 327
EP 334
DI 10.1097/COH.0b013e32833a0b9b
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NJ
UT WOS:000295508200011
PM 20543609
ER
PT J
AU Kim, SY
Janeway, K
Pappo, A
AF Kim, Su Y.
Janeway, Katherine
Pappo, Alberto
TI Pediatric and wild-type gastrointestinal stromal tumor: new therapeutic
approaches
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE molecular targeting; pediatric gastrointestinal stromal tumor; rare
disorders
ID OF-THE-LITERATURE; IMATINIB MESYLATE; SARCOMA GROUP; YOUNG-ADULTS;
SOFT-TISSUE; PHASE-III; MUTATIONS; BIOLOGY; KIT; CHILDREN
AB Purpose of review
Pediatric gastrointestinal stromal tumor is an uncommon tumor, the rarity of which has made both laboratory research studies and clinical management very difficult. As we learn more about this disorder, what is emerging is that this rare cancer is markedly different in children and adults. One of the main biological differences is that pediatric patients lack activating mutations in the oncogenes that drive tumor formation in adults. The natural history of this disease also appears to be more indolent in children than in adults. In this review, we will discuss the differences between children and adults with gastrointestinal stromal tumor and some new potential therapeutic agents.
Recent findings
This review discusses recent advances and the rationale for several recently identified molecular targets. In addition, we discuss the formation of a clinic at the National Institutes of Health that is dedicated to the study of this rare disorder.
Summary
Collaborative efforts are underway to better define the natural history and clinical course of pediatric patients with gastrointestinal stromal tumor. When combined with innovative genomic and molecular studies, these dual approaches will allow for notable advances in this field.
C1 [Kim, Su Y.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Janeway, Katherine] Boston Childrens Hosp, Boston, MA USA.
[Pappo, Alberto] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
RP Kim, SY (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC 1W-3750, Bethesda, MD 20892 USA.
EM kimsuyou@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011196-01]
NR 28
TC 7
Z9 8
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD JUL
PY 2010
VL 22
IS 4
BP 347
EP 350
DI 10.1097/CCO.0b013e32833aaae7
PG 4
WC Oncology
SC Oncology
GA 615QL
UT WOS:000279150200010
PM 20485167
ER
PT J
AU Speranza, G
Doroshow, JH
Kummar, S
AF Speranza, Giovanna
Doroshow, James H.
Kummar, Shivaani
TI Adenocarcinoma of the small bowel: changes in the landscape?
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE adenocarcinoma; chemotherapy; small bowel cancer
ID DOUBLE-BALLOON ENTEROSCOPY; SMALL-INTESTINE; MICROSATELLITE INSTABILITY;
PROGNOSTIC-FACTORS; CAPSULE ENDOSCOPY; COMBINATION CHEMOTHERAPY;
GASTROINTESTINAL-TRACT; SURGICAL-MANAGEMENT; PHASE-II; 5-FLUOROURACIL
AB Purpose of review
Small bowel adenocarcinoma (SBA) is a rare cancer with a poor prognosis and little information to guide its management. In recent years, improved diagnostic imaging and an increase in reported experience with use of chemotherapy may alter the way we manage SBA. This review will summarize recent advances in characterization, imaging, and treatment of SBA.
Recent findings
Recent advances in less invasive imaging tools may permit earlier and increased diagnosis of SBA. Surgery remains the mainstay of treatment, and the role of adjuvant chemotherapy is still unclear. However, the use of adjuvant therapy is increasing. Chemotherapy with newer regimens may provide clinical benefit in the metastatic setting. Nearly all results are from retrospective studies. Targeted therapies have not been extensively studied.
Summary
The rarity of the disease and difficulty in diagnosis contribute to the lack of prospective trials evaluating therapies for SBA. Retrospective studies suggest a benefit for combination chemotherapy regimens. Prospective evaluation of newer chemotherapeutic agents and targeted therapies is needed to improve outcomes in this disease.
C1 [Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Speranza, Giovanna; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Kummar, S (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,10-13N240G, Bethesda, MD 20892 USA.
EM kummars@mail.nih.gov
FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research
of the National Cancer Institute; NIH, National Cancer Institute, Center
for Cancer Research
FX This paper was written with support from the Division of Cancer
Treatment and Diagnosis and the Center for Cancer Research of the
National Cancer Institute. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the United States
Government. This work was supported by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 43
TC 6
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD JUL
PY 2010
VL 22
IS 4
BP 387
EP 393
DI 10.1097/CCO.0b013e32833a86fe
PG 7
WC Oncology
SC Oncology
GA 615QL
UT WOS:000279150200017
PM 20485170
ER
PT J
AU Mattai, AK
Hill, JL
Lenroot, RK
AF Mattai, Anand K.
Hill, Julia L.
Lenroot, Rhoshel K.
TI Treatment of early-onset schizophrenia
SO CURRENT OPINION IN PSYCHIATRY
LA English
DT Article
DE adolescent; antipsychotic; child; schizophrenia
ID RANDOMIZED CONTROLLED-TRIAL; ULTRA-HIGH RISK; SPECTRUM DISORDERS TEOSS;
2ND-GENERATION ANTIPSYCHOTICS; DOUBLE-BLIND; ADVERSE EVENTS;
YOUNG-PEOPLE; FOLLOW-UP; CHILDREN; ADOLESCENTS
AB Purpose of review
Treatment of children who develop schizophrenia in childhood and early adolescence presents unique considerations. There has been increasing attention to the importance of early intervention and whether treatment effects may be affected by brain development.
Recent findings
Several recent trials support the use of antipsychotics for treatment of schizophrenia in children and adolescents. Clozapine shows greater efficacy in children and adolescents than it has in adults. A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. Data regarding effects of antipsychotics on brain development in children and young adolescents with schizophrenia are sparse, although one report found no difference between effects of clozapine and olanzapine on cortical thickness.
Summary
Although psychosocial interventions are an important adjunctive treatment, antipsychotic medications continue to be the mainstay of treatment. Careful monitoring of metabolic side effects and age-appropriate intervention is particularly important, as children and adolescents appear to be more likely to develop metabolic abnormalities such as pronounced weight gain, which may significantly impact adherence as well as lead to other health issues.
C1 [Hill, Julia L.; Lenroot, Rhoshel K.] Prince Wales Med Res Inst, Randwick, NSW 2031, Australia.
[Hill, Julia L.; Lenroot, Rhoshel K.] Univ New S Wales, Sydney, NSW 2052, Australia.
[Mattai, Anand K.; Lenroot, Rhoshel K.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Lenroot, RK (reprint author), Prince Wales Med Res Inst, Corner Barker & Easy St, Randwick, NSW 2031, Australia.
EM R.lenroot@unsw.edu.au
RI Hill, Julia/A-4028-2012
FU National Institute of Mental Health
FX This work was supported by the Intramural Program of the National
Institute of Mental Health.
NR 66
TC 23
Z9 25
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7367
J9 CURR OPIN PSYCHIATR
JI Curr. Opin. Psychiatr.
PD JUL
PY 2010
VL 23
IS 4
BP 304
EP 310
DI 10.1097/YCO.0b013e32833b027e
PG 7
WC Psychiatry
SC Psychiatry
GA 607WD
UT WOS:000278537100002
PM 20502331
ER
PT J
AU Kolch, M
Ludolph, AG
Plener, PL
Fangerau, H
Vitiello, B
Fegert, JM
AF Koelch, Michael
Ludolph, Andrea G.
Plener, Paul L.
Fangerau, Heiner
Vitiello, Benedetto
Fegert, Joerg M.
TI Safeguarding Children's Rights in Psychopharmacological Research:
Ethical and Legal Issues
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Review
DE Ethics; psychopharmacology; research; children and adolescents
ID SEROTONIN REUPTAKE INHIBITORS; TRULY INDEPENDENT RESEARCH;
CLINICAL-TRIALS; PEDIATRIC PSYCHOPHARMACOLOGY; OFF-LABEL; ADOLESCENT
PSYCHOPHARMACOLOGY; MULTIMODAL TREATMENT; DEVELOPING-COUNTRIES;
INFORMED-CONSENT; DEVELOPING-WORLD
AB Objective: Research on psychopharmacological treatment in children and adolescents is the subject of ongoing ethical discussion, as minors with mental disorders constitute a vulnerable patient group. Considering the important legislative changes in pediatric research over the past decade in both the US and Western Europe, there is a need to review recent developments in this area.
Method: Based on a systematic literature review, a hermeneutical analysis focusing the main issues of ethics in child and adolescent psychopharmacology is provided. Legal and regulatory aspects of psychopharmacological research in children are compared between the US and Europe. Relevant issues were informed assent and consent to research participation, minimal risk and burden of research, ethics of pharmacogenetics, research on "me-too" medications, and justice in global research. Additionally, the concern about undue influence of financial interests in research is also addressed.
Conclusion: Incentives for the conduct of clinical trials with children comparable to those contained in US legislation are now provided in the EU. Research to develop "me-too" preparations may have no significant benefit for children, but can cause research burden and detract from clinically more important projects by utilizing limited investigator time and patient resources. Thus far, pharmacogenetic studies may bring more individualized treatment approaches into child psychiatry but they remain at present a promise for the future. Finally, the issues of avoiding undue influence from funders and conflicts of interest remain a prominent concern which can be solved by declaring conflicts and publishing all results of studies extensively.
C1 [Koelch, Michael; Ludolph, Andrea G.; Plener, Paul L.; Fegert, Joerg M.] Univ Hosp Ulm, Dept Child & Adolescent Psychiat & Psychotherapy, D-89075 Ulm, Germany.
[Fangerau, Heiner] Univ Ulm, Inst Hist Philosophy & Eth Med, D-89069 Ulm, Germany.
[Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA.
RP Kolch, M (reprint author), Univ Hosp Ulm, Dept Child & Adolescent Psychiat & Psychotherapy, Steinhovelstr 5, D-89075 Ulm, Germany.
EM michael.koelch@uniklinik-ulm.de
RI Ludolph, Andrea/G-2567-2014
FU Eli Lilly International Foundation; German Ministries for Family
Affairs, Senior Citizens, Women and Youth; Schweizer Bundesamt fur
Justiz; Boehringer Ingelheim; Janssen-Cilag; University of Rostock;
DGKJPP; UCB; Europ ische Akademie; UCB/Celltech; Medice and Janssen;
UCB/Celltech and Medice; Volkswagen foundation; Eberhardt foundation;
Eli Lilly Foundation; Janssen; Celltech/USB; Aventis; Bayer; Bristol-MS;
JJ; Lilly; Medice; Novartis; Pfizer; Ratiopharm; Sanofi-Synthelabo;
Servier; VFA & Generikaverband; Vatican; NIMH; AACAP; DFG; EU; European
Academy
FX M. Koelch is an employee of the University Hospital of Ulm. He received
an unrestricted grant by the Eli Lilly International Foundation for
studies on information of minors involved in clinical research. MK
received further research grants in the last five years by German
Ministries for Family Affairs, Senior Citizens, Women and Youth, and for
Research and Education (BMFFSJ, BMBF), Schweizer Bundesamt fur Justiz,
Boehringer Ingelheim,. Clinical investigator or principal investigator
in trials of Eli Lilly, Astra Zeneca, Janssen-Cilag. Travel grants or
payments for lectures by Janssen-Cilag, University of Rostock, DGKJPP,
UCB, Europ ische Akademie, various non-profit organizations. No
stockholder or share-holder in pharmaceutical industry.; A.G. Ludolph
reports having received lecture fees from UCB/Celltech, Medice and
Janssen, and research funding from UCB/Celltech and Medice. She is
involved in clinical trials with Bohringer Ingelheim, Eli Lilly,
Janssen-Cilag.; J.M. Fegert got unrestricted research grants from State
and national governmental organizations and from the Volkswagen
foundation, the Eberhardt foundation, from Eli Lilly Foundation, from
Janssen and from Celltech/USB. Travel grants from or served as a
consultant for Aventis, Bayer, Bristol-MS, J&J, Celltech/USB, Lilly,
Medice, Novartis, Pfizer, Ratiopharm, Sanofi-Synthelabo; Servier, VFA &
Generikaverband, the Vatican, NIMH, AACAP, DFG, EU and European Academy.
He was involved in clinical trials with Janssen, Medice, Lilly, Astra
Zeneca and serves DSMB for Pfizer. No shares and no direct affiliation
with a pharmaceutical company.
NR 106
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PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD JUL
PY 2010
VL 16
IS 22
BP 2398
EP 2406
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 633BD
UT WOS:000280473600002
PM 20513231
ER
PT J
AU Chattopadhyay, PK
Roederer, M
AF Chattopadhyay, Pratip K.
Roederer, Mario
TI Good Cell, Bad Cell: Flow Cytometry Reveals T-cell Subsets Important in
HIV Disease
SO CYTOMETRY PART A
LA English
DT Review
DE flow cytometry; HIV; T-cells
ID ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTER AIDS COHORT; CD38
ANTIGEN-EXPRESSION; LYMPHOCYTE-ACTIVATION; PROGRAMMED DEATH-1; IMMUNE
ACTIVATION; INFECTED PATIENTS; PD-1 EXPRESSION; HTLV-III/LAV; VIRAL LOAD
AB Flow cytometry is a key technology in the study of HIV disease. In this article, we review various cellular markers that can be measured in the setting of pathogenesis or vaccination studies, including markers of activation, differentiation, senescence, immune suppression, and function In addition, we discuss important considerations for making these measurements Finally, we examine how flow cytometry studies have taught researchers about the disease process, and the potential for flow cytometry technology to guide treatment decisions and evaluate vaccine candidates in the future Published 2010 Wiley-Liss, Inc dagger
C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD USA.
RP Chattopadhyay, PK (reprint author), NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Room 5509,40 Convent Dr, Bethesda, MD USA.
RI Chattopadhyay, Pratip/B-9227-2008;
OI Chattopadhyay, Pratip/0000-0002-5457-9666
FU Intramural NIH HHS [Z99 AI999999]
NR 97
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Z9 38
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD JUL
PY 2010
VL 77A
IS 7
SI SI
BP 614
EP 622
DI 10.1002/cyto.a.20905
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 621LZ
UT WOS:000279581600004
PM 20583275
ER
PT J
AU Lugli, E
Roederer, M
Cossarizza, A
AF Lugli, Enrico
Roederer, Mario
Cossarizza, Andrea
TI Data Analysis in Flow Cytometry: The Future Just Started
SO CYTOMETRY PART A
LA English
DT Review
DE polychromatic flow cytometry, data analysis, lymphocytes; T cells;
immune system
ID PRINCIPAL COMPONENT ANALYSIS; T-CELLS; CLUSTER-ANALYSIS; DISTRIBUTION
DIFFERENCES/; MULTIPARAMETER DATA; POSITIVE CELLS; IDENTIFICATION;
EXPRESSION; CLASSIFICATION; HETEROGENEITY
AB In the last 10 years, a tremendous progress characterized flow cytometry in its different aspects. In particular, major advances have been conducted regarding the hardware/instrumentation and reagent development, thus allowing fine cell analysis up to 20 parameters As a result, this technology generates very complex damsels that demand for the development of optimal tools of analysis Recently, many independent research groups approached the problem by using both supervised and unsupervised methods In this article, we will review the new developments concerning the use of bioinformatics for polychromatic flow cytometry and propose what should be done to unravel the enormous heterogeneity of the cells we interrogate each day. Published 2010 Inc dagger
C1 [Lugli, Enrico] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Cossarizza, Andrea] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41125 Modena, Italy.
RP Lugli, E (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
OI Cossarizza, Andrea/0000-0002-5381-1558
FU National Institutes of Health, Vaccine Research Center, National
Institutes of Allergy and Infectious Diseases; Istituto Superiore di
Sanita', Rome, Italy [30G 62, 40G 62]; MIUR
FX Grant Sponsor This work was sponsored by the Intramural Research program
of the National Institutes of Health, Vaccine Research Center, National
Institutes of Allergy and Infectious Diseases (EL and M R), and by VI
Programma Nazionale di Ricerca sull'AIDS 2006 (Istituto Superiore di
Sanita', Rome, Italy), grants No 300 62 and 40G 62 to AC, and by a grant
from MIUR - PRIN 2008 (Project: 'Regulation of Lon protease expression
in response to oxidative damage to mitochondria') to A C
NR 43
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U1 3
U2 33
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD JUL
PY 2010
VL 77A
IS 7
SI SI
BP 705
EP 713
DI 10.1002/cyto.a.20901
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 621LZ
UT WOS:000279581600013
PM 20583274
ER
PT J
AU Britton, JC
Stewart, SE
Killgore, WDS
Rosso, IM
Price, LM
Gold, AL
Pine, DS
Wilhelm, S
Jenike, MA
Rauch, SL
AF Britton, Jennifer C.
Stewart, S. Evelyn
Killgore, William D. S.
Rosso, Isabelle M.
Price, Lauren M.
Gold, Andrea L.
Pine, Daniel S.
Wilhelm, Sabine
Jenike, Michael A.
Rauch, Scott L.
TI AMYGDALA ACTIVATION IN RESPONSE TO FACIAL EXPRESSIONS IN PEDIATRIC
OBSESSIVE-COMPULSIVE DISORDER
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE OCD; fMRI; neuroimaging; anxiety disorder; fear; disgust
ID GENERALIZED SOCIAL PHOBIA; MEDIAL PREFRONTAL CORTEX;
POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL
GLUCOSE-METABOLISM; BRAIN ACTIVATION; MAJOR DEPRESSION; EMOTIONAL FACES;
ANTIDEPRESSANT TREATMENT; SYMPTOM PROVOCATION
AB Background: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OLD,) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916-920]. Methods: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N = 12) and a HC sample (N = 17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. Results: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. Conclusions: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific. Depression and Anxiety 27:643-651, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Britton, Jennifer C.; Pine, Daniel S.] NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Britton, Jennifer C.; Killgore, William D. S.; Rosso, Isabelle M.; Price, Lauren M.; Gold, Andrea L.; Rauch, Scott L.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA.
[Stewart, S. Evelyn; Wilhelm, Sabine; Jenike, Michael A.; Rauch, Scott L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stewart, S. Evelyn] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Gold, Andrea L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
RP Britton, JC (reprint author), NIH, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 15K, Bethesda, MD 20892 USA.
EM brittonjen@mail.nih.gov
RI Britton, Jennifer/J-4501-2013; Stewart, Evelyn/K-6961-2014;
OI Gold, Andrea/0000-0003-4447-776X; Killgore, William/0000-0002-5328-0208;
Stewart, S. Evelyn/0000-0002-0994-6383
FU David Judah Fund; National Institutes of Health; National Institute of
Mental Health
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsors: David Judah Fund; The Intramural
Research Program of the National Institutes of Health and the National
Institute of Mental Health.
NR 71
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U1 4
U2 11
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUL
PY 2010
VL 27
IS 7
BP 643
EP 651
DI 10.1002/da.20718
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 622KY
UT WOS:000279663900003
PM 20602430
ER
PT J
AU Kim, P
Leckman, JF
Mayes, LC
Newman, MA
Feldman, R
Swain, JE
AF Kim, Pilyoung
Leckman, James F.
Mayes, Linda C.
Newman, Michal-Ann
Feldman, Ruth
Swain, James E.
TI Perceived quality of maternal care in childhood and structure and
function of mothers' brain
SO DEVELOPMENTAL SCIENCE
LA English
DT Article
ID PARENTAL BONDING INSTRUMENT; MIRROR-NEURON SYSTEM; INTERGENERATIONAL
TRANSMISSION; INFANT SYNCHRONY; ORBITOFRONTAL CORTEX; HIPPOCAMPAL
VOLUME; STRESS REACTIVITY; SOCIAL COGNITION; HUMAN AMYGDALA; BEHAVIOR
AB Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers.
C1 [Kim, Pilyoung] NIMH, Anxiety Program, NIH, Bethesda, MD 20892 USA.
[Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Newman, Michal-Ann; Feldman, Ruth; Swain, James E.] Yale Univ, Sch Med, Ctr Child Study, Yale Program Risk Resilience & Recovery, New Haven, CT 06520 USA.
[Mayes, Linda C.] Anna Freud Ctr, London, England.
[Feldman, Ruth] Bar Ilan Univ, Susan Gonda Brain Sci Ctr, IL-52100 Ramat Gan, Israel.
[Swain, James E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Kim, P (reprint author), NIMH, Anxiety Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Pilyoung.kim@nih.gov
RI Swain, James/F-7270-2013
OI Swain, James/0000-0001-8440-0658
FU NIMH NIH HHS [T32 MH018268]
NR 74
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U1 2
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1363-755X
J9 DEVELOPMENTAL SCI
JI Dev. Sci.
PD JUL
PY 2010
VL 13
IS 4
BP 662
EP 673
DI 10.1111/j.1467-7687.2009.00923.x
PG 12
WC Psychology, Developmental; Psychology, Experimental
SC Psychology
GA 611FQ
UT WOS:000278797600013
PM 20590729
ER
PT J
AU Pociot, F
Akolkar, B
Concannon, P
Erlich, HA
Julier, C
Morahan, G
Nierras, CR
Todd, JA
Rich, SS
Nerup, J
AF Pociot, Flemming
Akolkar, Beena
Concannon, Patrick
Erlich, Henry A.
Julier, Cecile
Morahan, Grant
Nierras, Concepcion R.
Todd, John A.
Rich, Stephen S.
Nerup, Jorn
TI Genetics of Type 1 Diabetes: What's Next?
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MAJOR HISTOCOMPATIBILITY COMPLEX; PANCREATIC
BETA-CELL; REGULATORY T-CELLS; EXTENDED HUMAN MHC; SUSCEPTIBILITY LOCUS;
MULTIPLEX FAMILIES; TYROSINE-PHOSPHATASE; AUTOIMMUNE-DISEASE; RISING
INCIDENCE
C1 [Pociot, Flemming; Nerup, Jorn] Hagedorn Res Inst, Dept Genome Biol, Gentofte, Denmark.
[Pociot, Flemming] Lund Univ, CRC, Malmo, Sweden.
[Akolkar, Beena] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Concannon, Patrick; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Concannon, Patrick] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Erlich, Henry A.] Roche Mol Syst, Pleasanton, CA USA.
[Julier, Cecile] INSERM, Ctr Natl Genotypage, U730, Evry, France.
[Morahan, Grant] Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Perth, WA 6009, Australia.
[Nierras, Concepcion R.] Juvenile Diabet Res Fdn Int, New York, NY USA.
[Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn Wellcome Trust Diabet & I, Cambridge Inst Med Res,Dept Med Genet, Cambridge CB2 2QQ, England.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
RP Pociot, F (reprint author), Hagedorn Res Inst, Dept Genome Biol, Gentofte, Denmark.
EM fpoc@hagedorn.dk
OI Concannon, Patrick/0000-0002-5801-1859; Pociot,
Flemming/0000-0003-3274-5448
FU National Institute of Allergy and Infectious Diseases (NIAID); National
Human Genome Research Institute (NHGRI); National Institute of Child
Health and Human Development (NICHD); Wellcome Trust; National Institute
for Health Research Cambridge Biomedical Centre; Juvenile Diabetes
Research Foundation International (JDRF); National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) [U01 DK062418]
FX This research uses resources provided by the Type 1 Diabetes Genetics
Consortium, a collaborative clinical study sponsored by the National
Institute of Allergy and Infectious Diseases (NIAID), National Human
Genome Research Institute (NHGRI), National Institute of Child Health
and Human Development (NICHD), the Wellcome Trust and the National
Institute for Health Research Cambridge Biomedical Centre, the Juvenile
Diabetes Research Foundation International (JDRF), and Grant U01
DK062418 from the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK).
NR 82
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U2 18
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUL
PY 2010
VL 59
IS 7
BP 1561
EP 1571
DI 10.2337/db10-0076
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 621WD
UT WOS:000279615100001
PM 20587799
ER
PT J
AU Pop-Busui, R
Evans, GW
Gerstein, HC
Fonseca, V
Fleg, JL
Hoogwerf, BJ
Genuth, S
Grimm, RH
Corson, MA
Prineas, R
AF Pop-Busui, Rodica
Evans, Gregory W.
Gerstein, Hertzel C.
Fonseca, Vivian
Fleg, Jerome L.
Hoogwerf, Byron J.
Genuth, Saul
Grimm, Richard H.
Corson, Marshall A.
Prineas, Ronald
CA ACCORD Study Grp
TI Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action
to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
SO DIABETES CARE
LA English
DT Article
ID INTENSIVE INSULIN THERAPY; NERVOUS-SYSTEM FUNCTION; BLOOD-GLUCOSE
CONTROL; COMPLICATIONS; NEUROPATHY; DISEASE; TYPE-1; ASSOCIATION;
MELLITUS; OUTCOMES
AB OBJECTIVE - Intensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.
RESEARCH DESIGN AND METHODS - CAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates.
RESULTS - During a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55-2.14 times as likely to die as participants without CAN, depending on the CAN definition used (P < 0.02 for all). The effect of allocation to the intensive group on all-cause and CVD mortality was similar in participants with or without CAN at baseline (P-interaction > 0.7).
CONCLUSIONS - Whereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
C1 [Pop-Busui, Rodica] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
[Evans, Gregory W.; Prineas, Ronald] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Gerstein, Hertzel C.] McMaster Univ Hamilton Hlth Sci, Hamilton, ON, Canada.
[Fonseca, Vivian] Tulane Univ, Endocrinol Sect, New Orleans, LA 70118 USA.
[Fleg, Jerome L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hoogwerf, Byron J.] Cleveland Clin, Cleveland, OH 44106 USA.
[Genuth, Saul] Case Western Reserve Univ, Div Endocrinol, Cleveland, OH 44106 USA.
[Grimm, Richard H.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
[Corson, Marshall A.] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA.
RP Pop-Busui, R (reprint author), Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
EM rpbusui@umich.edu
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases; National
Institutes of Health, National Institute on Aging; National Institutes
of Health, National Eye Institute; Centers for Disease Control and
Prevention; General Clinical Research Centers
FX This work was supported by contracts and interagency agreements
(N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182,
N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the
National Heart, Lung, and Blood Institute; by other components of the
National Institutes of Health, including the National Institute of
Diabetes and Digestive and Kidney Diseases, the National Institute on
Aging, and the National Eye Institute; by the Centers for Disease
Control and Prevention; and by General Clinical Research Centers. The
following companies provided study medications, equipment, or supplies:
Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer
HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals,
Merck, Novartis, Novo Nordisk, Omron Healthcare, sanofi-aventis, and
Schering-Plough.
NR 25
TC 125
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U1 1
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2010
VL 33
IS 7
BP 1578
EP 1584
DI 10.2337/dc09-0125
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 656SL
UT WOS:000282356800033
PM 20215456
ER
PT J
AU Liu, JK
Fox, CS
Hickson, D
Sarpong, D
Ekunwe, L
May, WD
Hundley, GW
Carr, JJ
Taylor, HA
AF Liu, Jiankang
Fox, Caroline S.
Hickson, DeMarc
Sarpong, Daniel
Ekunwe, Lynette
May, Warren D.
Hundley, Gregory W.
Carr, J. Jeffery
Taylor, Herman A.
TI Pericardial Adipose Tissue, Atherosclerosis, and Cardiovascular Disease
Risk Factors The Jackson Heart Study
SO DIABETES CARE
LA English
DT Article
ID METABOLIC SYNDROME; EPICARDIAL FAT; CORONARY ATHEROSCLEROSIS;
ASSOCIATION; OBESITY
AB OBJECTIVE - Pericardial adipose tissue (PAT), a regional fat depot that surrounds the heart, is associated with an unfavorable cardiometabolic risk factor profile. The associations among PAT, cardiometabolic risk factors, and coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) in African American populations have not been explored.
RESEARCH DESIGN AND METHODS - A total of 1,414 African Americans (35% men; mean +/- SD age 58 +/- 11 years) drawn from the Jackson Heart Study (JHS) underwent multidetector computed tomography assessment of abdominal visceral adipose tissue (VAT) and PAT between 2007 and 2009. Cardiometabolic risk factors, CAC, and AAC were examined in relation to increments of PAT and VAT.
RESULTS - PAT was significantly correlated with BMI, waist circumference, and VAT (r = 0.35, 0.46, and 0.69; all P < 0.0001). PAT (per 1-SD increase) was associated with elevated levels of systolic blood pressure (P < 0.04), fasting glucose, triglycerides, and C-reactive protein and lower levels of HDL (all P values<0.0001). PAT was also associated with metabolic syndrome (odds ratio [OR] 1.89; P < 0.0001), hypertension (1.48; P < 0.0006), and diabetes (1.40; P < 0.04); all associations were diminished after further adjustment for VAT (most P > 0.05). However, the association of PAT with CAC but not with AAC remained significant (OR 1.34 [95% Cl 1.10-1.64]; P < 0.004) after multivariable and VAT adjustment.
CONCLUSIONS - PAT is significantly correlated with most cardiometabolic risk factors and CAC in the JHS cohort. The results suggest that PAT is an important VAT depot that may exert a local effect on the coronary vasculature.
C1 [Liu, Jiankang; Hickson, DeMarc; Sarpong, Daniel; Ekunwe, Lynette; Taylor, Herman A.] Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39217 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[May, Warren D.] Jackson State Univ, Univ Mississippi, Med Ctr, Dept Prevent Med, Jackson, MS USA.
[Hundley, Gregory W.; Carr, J. Jeffery] Wake Forest Univ, Bowman Gray Sch Med, Dept Cardiol & Radiol, Winston Salem, NC USA.
RP Liu, JK (reprint author), Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39217 USA.
EM jliu@medicine.umsmed.edu
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Center on Minority Health and Health Disparities; National
Heart, Lung, and Blood Institute [N01-HC-95170, N01-HC-95171,
N01-C-95172]
FX The Jackson Heart Study is supported by the National Heart, Lung, and
Blood Institute and the National Center on Minority Health and Health
Disparities. Funding for H.A.T. was provided under contracts
N01-HC-95170, N01-HC-95171, and N01-C-95172 from the National Heart,
Lung, and Blood Institute and the National Center on Minority Health and
Health Disparities.
NR 21
TC 35
Z9 37
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2010
VL 33
IS 7
BP 1635
EP 1639
DI 10.2337/dc10-0245
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 656SL
UT WOS:000282356800044
PM 20413524
ER
PT J
AU Bian, L
Hanson, RL
Muller, YL
Ma, L
Kobes, S
Knowler, WC
Bogardus, C
Baier, LJ
AF Bian, L.
Hanson, R. L.
Muller, Y. L.
Ma, L.
Kobes, S.
Knowler, W. C.
Bogardus, C.
Baier, L. J.
CA MAGIC Investigators
TI Variants in ACAD10 are associated with type 2 diabetes, insulin
resistance and lipid oxidation in Pima Indians
SO DIABETOLOGIA
LA English
DT Article
DE Acyl-coenzyme A dehydrogenase 10; Association; Insulin resistance;
Linkage disequilibrium; Lipid oxidation; Pima Indians; Type 2 diabetes
ID GENOME
AB A prior genome-wide association study in Pima Indians identified a variant within the ACAD10 gene that is associated with early-onset type 2 diabetes. Acyl-coenzyme A dehydrogenase 10 (ACAD10) catalyses mitochondrial fatty acid beta-oxidation, which plays a pivotal role in developing insulin resistance and type 2 diabetes. Therefore, ACAD10 was analysed as a positional and biological candidate for type 2 diabetes.
Twenty-three SNPs were genotyped in 1,500 Pima Indians to determine the linkage disequilibrium pattern across ACAD10. Association with type 2 diabetes was determined by genotyping four tag single nucleotide polymorphisms (SNPs) in a population-based sample of 3,501 full-heritage Pima Indians; two associated SNPs were further genotyped in a second population-based sample of 3,723 American Indians. Associations with quantitative traits were assessed in 415 non-diabetic full heritage Pima individuals who had been metabolically phenotyped.
SNPs rs601663 and rs659964 were associated with type 2 diabetes in the full-heritage Pima Indian sample (p = 0.04 and 0.0006, respectively), and rs659964 was further associated with type 2 diabetes in the second American Indian sample (p = 0.04). Combination of these two samples provided the strongest evidence for association (p = 0.009 and 0.00007, for rs601663 and rs659964, respectively). Quantitative trait analyses identified nominal associations with both lower lipid oxidation rate and larger subcutaneous abdominal adipocyte size, which is consistent with the known physiology of ACAD10, and also identified associations with increased insulin resistance.
We propose that ACAD10 variation may increase type 2 diabetes susceptibility by impairing insulin sensitivity via abnormal lipid oxidation.
C1 [Bian, L.; Hanson, R. L.; Muller, Y. L.; Ma, L.; Kobes, S.; Knowler, W. C.; Bogardus, C.; Baier, L. J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 445 N 5th St,Suite 210, Phoenix, AZ 85004 USA.
EM lbaier@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institutes of Health (NIH); American Diabetes
Association
FX This study was supported by the intramural research programme of the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health (NIH). L. Bian is supported by a
mentor grant (to C. Bogardus) from the American Diabetes Association. We
thank all the participants from the Gila River Indian Community. We
thank J.E. Foley and P. Thuillez (both are from NIDDK, NIH) for their
work in determining lipolysis within the isolated adipocytes.
NR 10
TC 10
Z9 10
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2010
VL 53
IS 7
BP 1349
EP 1353
DI 10.1007/s00125-010-1695-y
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 602DM
UT WOS:000278118700013
PM 20390405
ER
PT J
AU Gorden, P
Lupsa, BC
Chong, AY
Lungu, AO
AF Gorden, P.
Lupsa, B. C.
Chong, A. Y.
Lungu, A. O.
TI Is there a human model for the 'metabolic syndrome' with a defined
aetiology?
SO DIABETOLOGIA
LA English
DT Letter
DE Insulin resistance; Leptin; Lipodystrophy; Metabolic syndrome
ID PROVISIONAL REPORT; CONSULTATION; DEFINITION; ADULTS; OBESE
C1 [Gorden, P.; Lupsa, B. C.; Chong, A. Y.; Lungu, A. O.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Gorden, P (reprint author), NIDDK, Clin Endocrinol Branch, NIH, MSC 1612,Room CRC 6-5940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM phillipg@intra.niddk.nih.gov
FU Intramural NIH HHS [Z99 DK999999]
NR 11
TC 11
Z9 11
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2010
VL 53
IS 7
BP 1534
EP 1536
DI 10.1007/s00125-010-1719-7
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 602DM
UT WOS:000278118700031
PM 20401463
ER
PT J
AU Aggarwal, M
Sommers, JA
Morris, C
Brosh, RM
AF Aggarwal, Monika
Sommers, Joshua A.
Morris, Christa
Brosh, Robert M., Jr.
TI Delineation of WRN helicase function with EXO1 in the replicational
stress response
SO DNA REPAIR
LA English
DT Article
DE Werner syndrome; Helicase; RecQ; rad50; Replicational stress; Genomic
instability
ID WERNER-SYNDROME PROTEIN; DOUBLE-STRAND BREAKS; HUMAN EXONUCLEASE 1;
S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; RECQ HELICASES;
DNA-REPAIR; HOMOLOGOUS RECOMBINATION; POLYMORPHIC VARIANT; FORK
PROGRESSION
AB The WRN gene defective in the premature aging disorder Werner syndrome encodes a helicase/exonuclease. We examined the ability of WRN to rescue DNA damage sensitivity of a yeast mutant defective in the Rad50 subunit of Mre11-Rad50-Xrs2 nuclease complex implicated in homologous recombination repair. Genetic studies revealed WRN operates in a yEXO1-dependent pathway to rescue rad50 sensitivity to methylmethane sulfonate (MMS). WRN helicase, but not exonuclease, is required for MMS resistance. WRN missense mutations in helicase or RecQ C-terminal domains interfered with the ability of WRN to rescue rad50 MMS sensitivity. WRN does not rescue rad50 ionizing radiation (IR) sensitivity, suggesting that WRN, in collaboration with yEXO1, is tailored to relieve replicational stress imposed by alkylated base damage. WRN and yEXO1 are associated with each other in vivo. Purified WRN stimulates hEXO1 nuclease activity on DNA substrates associated with a stalled or regressed replication fork. We propose WRN helicase operates in an EXO1-dependent pathway to help cells survive replicational stress. In contrast to WRN, BLM helicase defective in Bloom's syndrome failed to rescue rad50 MMS sensitivity, but partially restored IR resistance, suggesting a delineation of function by the human RecQ helicases. Published by Elsevier B.V.
C1 [Aggarwal, Monika; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA.
[Morris, Christa] NIA, Flow Cytometry Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Rm 06B125, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU Intramural NIH HHS [ZIA AG000741-09, Z01 AG000752-01]
NR 51
TC 14
Z9 14
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD JUL 1
PY 2010
VL 9
IS 7
BP 765
EP 776
DI 10.1016/j.dnarep.2010.03.014
PG 12
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 626KF
UT WOS:000279964200005
PM 20447876
ER
PT J
AU Akbari, M
Solvang-Garten, K
Hanssen-Bauer, A
Lieske, NV
Pettersen, HS
Pettersen, GK
Wilson, DM
Krokan, HE
Otterlei, M
AF Akbari, Mansour
Solvang-Garten, Karin
Hanssen-Bauer, Audun
Lieske, Nora Valeska
Pettersen, Henrik Sahlin
Pettersen, Grete Klippenvag
Wilson, David M., III
Krokan, Hans E.
Otterlei, Marit
TI Direct interaction between XRCC1 and UNG2 facilitates rapid repair of
uracil in DNA by XRCC1 complexes
SO DNA REPAIR
LA English
DT Article
DE Base excision repair; XRCC1; UNG2; DNA repair complexes; Replication
associated repair
ID BASE EXCISION-REPAIR; STRAND-BREAK REPAIR; SISTER-CHROMATID EXCHANGE;
POLY(ADP-RIBOSE) POLYMERASE; PHYSICALLY INTERACTS; MOLECULAR-CLONING;
REPLICATION FOCI; CELL-EXTRACTS; LIGASE-III; IN-VITRO
AB Uracil-DNA glycosylase, UNG2, interacts with PCNA and initiates post-replicative base excision repair (BER) of uracil in DNA. The DNA repair protein XRCC1 also co-localizes and physically interacts with PCNA. However, little is known about whether UNG2 and XRCC1 directly interact and participate in a same complex for repair of uracil in replication foci. Here, we examine localization pattern of these proteins in live and fixed cells and show that UNG2 and XRCC1 are likely in a common complex in replication foci. Using pull-down experiments we demonstrate that UNG2 directly interacts with the nuclear localization signal-region (NLS) of XRCC1. Western blot and functional analysis of immunoprecipitates from whole cell extracts prepared from S-phase enriched cells demonstrate the presence of XRCC1 complexes that contain UNG2 in addition to separate XRCC1 and UNG2 associated complexes with distinct repair features. XRCC1 complexes performed complete repair of uracil with higher efficacy than UNG2 complexes. Based on these results, we propose a model for a functional role of XRCC1 in replication associated BER of uracil. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Akbari, Mansour; Solvang-Garten, Karin; Hanssen-Bauer, Audun; Lieske, Nora Valeska; Pettersen, Henrik Sahlin; Pettersen, Grete Klippenvag; Krokan, Hans E.; Otterlei, Marit] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway.
[Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Otterlei, M (reprint author), Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway.
EM marit.otterlei@ntnu.no
RI Pettersen, Henrik Sahlin/B-9901-2011;
OI Akbari, Mansour/0000-0002-6490-7766
FU Research Council of Norway; St. Olav's Hospital, Trondheim, Norway;
Norwegian Cancer Society; Svanhild and Arne Must Fund; European Union;
NIH, National Institute on Aging, USA
FX We would like to thank Ruth Haaland Krokan and Nina-Beate Liabakk for
technical assistance. This work is supported by The Research Council of
Norway, The National Programme for Research in Functional Genomics in
Norway (FUGE) in The Research Council of Norway, The Cancer Fund at St.
Olav's Hospital, Trondheim, Norway, The Norwegian Cancer Society, The
Svanhild and Arne Must Fund for Medical Research, Norway, Integrated
Project on DNA Repair Supported by European Union and the Intramural
Research Program of the NIH, National Institute on Aging, USA.
NR 47
TC 28
Z9 28
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD JUL 1
PY 2010
VL 9
IS 7
BP 785
EP 795
DI 10.1016/j.dnarep.2010.04.002
PG 11
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 626KF
UT WOS:000279964200007
PM 20466601
ER
PT J
AU Rossi, ML
Ghosh, AK
Kulikowicz, T
Croteau, DL
Bohr, VA
AF Rossi, Marie L.
Ghosh, Avik K.
Kulikowicz, Tomasz
Croteau, Deborah L.
Bohr, Vilhelm A.
TI Conserved helicase domain of human RecQ4 is required for strand
annealing-independent DNA unwinding
SO DNA REPAIR
LA English
DT Article
DE DNA repair; Aging; RecQ helicase; Helicases; Replication protein A
ID ROTHMUND-THOMSON-SYNDROME; REPLICATION PROTEIN-A; WERNER-SYNDROME
PROTEIN; SYNDROME GENE-PRODUCT; NUCLEOTIDE EXCISION-REPAIR;
BLOOMS-SYNDROME PROTEIN; FLAP ENDONUCLEASE-1; CATALYTIC-ACTIVITIES;
SECONDARY STRUCTURE; GENOMIC STABILITY
AB Humans have five members of the well conserved RecQ helicase family: RecQ1, Bloom syndrome protein (BLM), Werner syndrome protein (WRN), RecQ4, and RecQ5, which are all known for their roles in maintaining genome stability. BLM, WRN, and RecQ4 are associated with premature aging and cancer predisposition. Of the three, RecQ4's biological and cellular roles have been least thoroughly characterized. Here we tested the helicase activity of purified human RecQ4 on various substrates. Consistent with recent results, we detected ATP-dependent RecQ4 unwinding of forked duplexes. However, our results provide the first evidence that human RecQ4's unwinding is independent of strand annealing, and that it does not require the presence of excess ssDNA. Moreover, we demonstrate that a point mutation of the conserved lysine in the Walker A motif abolished helicase activity, implying that not the N-terminal portion, but the helicase domain is solely responsible for the enzyme's unwinding activity. In addition, we demonstrate a novel stimulation of RecQ4's helicase activity by replication protein A, similar to that of RecQ1, BLM, WRN, and RecQ5. Together, these data indicate that specific biochemical activities and protein partners of RecQ4 are conserved with those of the other RecQ helicases. Published by Elsevier B.V.
C1 [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM BohrV@grc.nia.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This work was supported entirely by funds from the Intramural Research
Program of the National Institutes of Health, National Institute on
Aging.
NR 67
TC 40
Z9 40
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD JUL 1
PY 2010
VL 9
IS 7
BP 796
EP 804
DI 10.1016/j.dnarep.2010.04.003
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 626KF
UT WOS:000279964200008
PM 20451470
ER
PT J
AU Jacobson, KA
Boeynaems, JM
AF Jacobson, Kenneth A.
Boeynaems, Jean-Marie
TI P2Y nucleotide receptors: promise of therapeutic applications
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID HUMAN P2Y(14) RECEPTOR; PLATELET-AGGREGATION; DENDRITIC CELLS;
EXTRACELLULAR NUCLEOTIDES; MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS;
NEUROPATHIC PAIN; HDL ENDOCYTOSIS; KNOCKOUT MICE; ANTAGONISTS
AB Extracellular nucleotides, such as ATP and UTP, have distinct signaling roles through a class of G-protein-coupled receptors, termed P2Y. The receptor ligands are typically charged molecules of low bioavailability and stability in vivo. Recent progress in the development of selective agonists and antagonists for P2Y receptors and study of knockout mice have led to new drug concepts based on these receptors. The rapidly accelerating progress in this field has already resulted in drug candidates for cystic fibrosis, dry eye disease and thrombosis. On the horizon are novel treatments for cardiovascular diseases, inflammatory diseases and neurodegeneration.
C1 [Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Boeynaems, Jean-Marie] Univ Libre Bruxelles, Inst Interdisciplinary Res, B-1070 Brussels, Belgium.
[Boeynaems, Jean-Marie] Erasme Univ Hosp, Dept Lab Med, B-1070 Brussels, Belgium.
RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z99 DK999999, ZIA DK031116-22]
NR 91
TC 76
Z9 79
U1 1
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD JUL
PY 2010
VL 15
IS 13-14
BP 570
EP 578
DI 10.1016/j.drudis.2010.05.011
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 627JB
UT WOS:000280034200010
PM 20594935
ER
PT J
AU Konno, Y
Kamino, H
Moore, R
Lih, F
Tomer, KB
Zeldin, DC
Goldstein, JA
Negishi, M
AF Konno, Yoshihiro
Kamino, Hiroki
Moore, Rick
Lih, Fred
Tomer, Kenneth B.
Zeldin, Darryl C.
Goldstein, Joyce A.
Negishi, Masahiko
TI The Nuclear Receptors Constitutive Active/Androstane Receptor and
Pregnane X Receptor Activate the Cyp2c55 Gene in Mouse Liver
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID ARACHIDONIC-ACID METABOLISM; CYTOCHROME-P450 CYP GENES; ANDROSTANE
RECEPTOR; GLUCOCORTICOID-RECEPTOR; TRANSCRIPTIONAL REGULATION; PHENYTOIN
INDUCTION; BLOOD-PRESSURE; EXPRESSION; MICE; CAR
AB Mouse CYP2C55 has been characterized as an enzyme that catalyzes synthesis of 19-hydroxyeicosatetraenoic acid (19-HETE), an arachidonic acid metabolite known to have important physiological functions such as regulation of renal vascular tone and ion transport. We have now found that CYP2C55 is induced by phenobarbital (PB) and pregnenolone 16 alpha-carbonitrile (PCN) in both mouse kidney and liver. The nuclear xenobiotic receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) regulate these drug inductions: CYP2C55 mRNA was increased 25-fold in PB-treated Car(+/+) but not in Car(-/-) mice and was induced in Pxr(+/+) but not Pxr(-/-) mice after PCN treatment. Cell-based promoter analysis and gel shift assays identified the DNA sequence (-1679)TGAACCCAGTTGAACT(-1664) as a DR4 motif that regulates CAR- and PXR-mediated transcription of the Cyp2c55 gene. Chronic PB treatment increased hepatic microsomal CYP2C55 protein and serum 19-HETE levels. These findings indicate that CAR and PXR may play a role in regulation of drug-induced synthesis of 19-HETE in the mouse.
C1 [Konno, Yoshihiro; Kamino, Hiroki; Moore, Rick; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Goldstein, Joyce A.] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Lih, Fred; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
RI Goldstein, Joyce/A-6681-2012; Tomer, Kenneth/E-8018-2013
FU National Institutes of Health National Institute of Environmental Health
[Z01-ES7100501, Z01-ES025034, Z01-ES050167, Z01-ES02124]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Institute of Environmental
Health Sciences [Grants Z01-ES7100501, Z01-ES025034, Z01-ES050167,
Z01-ES02124] (to M.N., D.C.Z., K.B.T., and J.A.G., respectively).
NR 42
TC 6
Z9 6
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD JUL
PY 2010
VL 38
IS 7
BP 1177
EP 1182
DI 10.1124/dmd.110.032334
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 631WU
UT WOS:000280382100021
PM 20371638
ER
PT J
AU Park, SH
Blackstone, C
AF Park, Seong H.
Blackstone, Craig
TI Further assembly required: construction and dynamics of the endoplasmic
reticulum network
SO EMBO REPORTS
LA English
DT Review
DE endoplasmic reticulum; hereditary spastic paraplegia; morphology;
reticulon; shaping
ID HEREDITARY SPASTIC PARAPLEGIA; AMYOTROPHIC-LATERAL-SCLEROSIS;
MEMBRANE-PROTEINS; NUCLEAR-ENVELOPE; LIVING CELLS; ER; ATLASTIN;
MICROTUBULES; ORGANIZATION; MECHANISMS
AB The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, ribosome-studded peripheral sheets and an interconnected network of smooth tubules extending throughout the cell. Although protein biosynthesis, transport and quality control in the ER have been studied extensively, mechanisms underlying the notably diverse architecture of the ER have only emerged recently; this review highlights these new findings and how they relate to ER functional specializations. Several protein families, including reticulons and DP1/REEPs/Yop1, harbour hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1 family of dynamin-related GTPases mediate the formation of three-way junctions that characterize the tubular ER network, and additional classes of hydrophobic hairpin-containing ER proteins interact with and remodel the microtubule cytoskeleton. Flat ER sheets have a different complement of proteins implicated in shaping, cisternal stacking and microtubule interactions. Finally, several shaping proteins are mutated in hereditary spastic paraplegias, emphasizing the particular importance of proper ER morphology and distribution for highly polarized cells.
C1 [Park, Seong H.; Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Neurogenet Branch, NIH, Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX The authors were supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 51
TC 68
Z9 68
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD JUL
PY 2010
VL 11
IS 7
BP 515
EP 521
DI 10.1038/embor.2010.92
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 618YJ
UT WOS:000279392000010
PM 20559323
ER
PT J
AU Geisbert, TW
Hensley, LE
Geisbert, JB
Leung, A
Johnson, JC
Grolla, A
Feldmann, H
AF Geisbert, Thomas W.
Hensley, Lisa E.
Geisbert, Joan B.
Leung, Anders
Johnson, Joshua C.
Grolla, Allen
Feldmann, Heinz
TI Postexposure Treatment of Marburg Virus Infection
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID EBOLA HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; PROTECTION; VECTORS
AB Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis virus-based vaccine is administered 20-30 min after infection with Marburg virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection.
C1 [Geisbert, Thomas W.] Boston Univ, Sch Med, Natl Emerging Infect Dis Labs Inst, Boston, MA 02118 USA.
[Hensley, Lisa E.; Johnson, Joshua C.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Leung, Anders; Grolla, Allen] Publ Hlth Agcy Canada, Winnipeg, MB, Canada.
[Feldmann, Heinz] NIH, Hamilton, MT USA.
RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Natl Emerging Infect Dis Labs Inst, 620 Albany St,Rm 401B, Boston, MA 02118 USA.
EM geisbert@bu.edu
OI Johnson, Joshua/0000-0002-5677-3841
FU Defense Threat Reduction Agency; Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; National Microbiology Laboratory of the Public
Health Agency of Canada
FX Funding was provided by the Defense Threat Reduction Agency, the
Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and the National
Microbiology Laboratory of the Public Health Agency of Canada.
NR 14
TC 34
Z9 36
U1 0
U2 2
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUL
PY 2010
VL 16
IS 7
BP 1119
EP 1122
DI 10.3201/eid1607.100159
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 620TG
UT WOS:000279522200011
PM 20587184
ER
PT J
AU Safronetz, D
Lopez, JE
Sogoba, N
Traore', SF
Raffel, SJ
Fischer, ER
Ebihara, H
Branco, L
Garry, RF
Schwan, TG
Feldmann, H
AF Safronetz, David
Lopez, Job E.
Sogoba, Nafomon
Traore', Sekou F.
Raffel, Sandra J.
Fischer, Elizabeth R.
Ebihara, Hideki
Branco, Luis
Garry, Robert F.
Schwan, Tom G.
Feldmann, Heinz
TI Detection of Lassa Virus, Mali
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID WEST-AFRICA; FEVER; RODENTIA
AB To determine whether Lassa virus was circulating in southern Mali, we tested samples from small mammals from 3 villages, including Soromba, where in 2009 a British citizen probably contracted a lethal Lassa virus infection. We report the isolation and genetic characterization of Lassa virus from an area previously unknown for Lassa fever.
C1 [Feldmann, Heinz] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Sogoba, Nafomon; Traore', Sekou F.] Univ Bamako, Bamako, Mali.
[Branco, Luis; Garry, Robert F.] Tulane Sch Med, New Orleans, LA USA.
[Branco, Luis] Autoimmune Technol LLC, New Orleans, LA USA.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
OI Branco, Luis/0000-0001-8161-0182
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. All laboratory work with potentially infectious
materials was conducted in a Biosafety Level 4 facility at the Rocky
Mountain Laboratories.
NR 15
TC 30
Z9 30
U1 0
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUL
PY 2010
VL 16
IS 7
BP 1123
EP 1126
DI 10.3201/eid1607.100146
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 620TG
UT WOS:000279522200012
PM 20587185
ER
PT J
AU Lang, PJ
AF Lang, Peter J.
TI Emotion and Motivation: Toward Consensus Definitions and a Common
Research Purpose
SO EMOTION REVIEW
LA English
DT Article
DE emotion theory; motivation; threat and reward; William James
AB Historically, the hypothesis driving emotion research has been that emotion's data-base-in language, physiology, and behavior-is organized around specific mental states, as reflected in evaluative language. It is suggested that this approach has not greatly advanced a natural science of emotion and that the developing motivational model of emotion defines a better path: emotion is an evolved trait founded on motivational neural circuitry shared by mammalian species, primitively prompting heightened perceptual processing and reflex mobilization for action to appetitive or threatening survival cues. As the field moves forward with increasingly sophisticated measurement technology and assessing more complex affective functioning, scientific understanding of human emotion will proceed best within the framework of this mammalian brain model.
C1 [Lang, Peter J.] Univ Florida, Ctr Study Emot & Attent, Gainesville, FL 32611 USA.
RP Lang, PJ (reprint author), Univ Florida, NIMH Ctr Study Emot & Attent, POB 112766, Gainesville, FL 32611 USA.
EM plang@phhp.ufl.edu
NR 40
TC 35
Z9 42
U1 4
U2 24
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1754-0739
J9 EMOT REV
JI Emot. Rev.
PD JUL
PY 2010
VL 2
IS 3
BP 229
EP 233
DI 10.1177/1754073910361984
PG 5
WC Psychology, Multidisciplinary
SC Psychology
GA V24CM
UT WOS:000208388500008
ER
PT J
AU Neumann, S
Huang, WW
Eliseeva, E
Titus, S
Thomas, CJ
Gershengorn, MC
AF Neumann, Susanne
Huang, Wenwei
Eliseeva, Elena
Titus, Steve
Thomas, Craig J.
Gershengorn, Marvin C.
TI A Small Molecule Inverse Agonist for the Human Thyroid-Stimulating
Hormone Receptor
SO ENDOCRINOLOGY
LA English
DT Article
ID THYROTROPIN RECEPTOR; MONOCLONAL-ANTIBODY; TSH RECEPTOR; ANTAGONIST;
MODULATORS; DOMAIN
AB Small molecule inverse agonists for the TSH receptor (TSHR) may be used as probes of the role of basal (or agonist-independent or constitutive) signaling and may have therapeutic potential as orally active drugs to inhibit basal signaling in patients with thyroid cancer and in some patients with hyperthyroidism. We describe the first small-molecule ligand [1;2-(3-((2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one] that exhibits inverse agonist properties at TSHR. 1 inhibits basal and TSH-stimulated signaling, measured as cAMP production, by TSHRs in HEK-EM 293 cells stably expressing wild-type TSHRs; the antagonism of TSH-mediated signaling is competitive. 1 also inhibits basal signaling by wild-type TSHRs, and four constitutively active mutants of TSHR expressed transiently in HEK-EM 293 cells. 1 was active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs where it inhibited basal levels of mRNA transcripts for thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR. These data serve as proof of principle that small, drug-like molecules can inhibit basal signaling by TSHR. We suggest that this small molecule is a lead compound for the development of higher-potency inverse agonists that can be used as probes of TSHR biology with therapeutic potential. (Endocrinology 151: 3454-3459, 2010)
C1 [Gershengorn, Marvin C.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Huang, Wenwei; Titus, Steve; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Human Genome Research Institute, National Institutes of Health;
National Institutes of Health
FX This research was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
National Human Genome Research Institute, National Institutes of Health
and the Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research.
NR 24
TC 18
Z9 20
U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUL
PY 2010
VL 151
IS 7
BP 3454
EP 3459
DI 10.1210/en.2010-0199
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 614IK
UT WOS:000279049300047
PM 20427476
ER
PT J
AU Karev, GP
AF Karev, Georgiy P.
TI Principle of Minimum Discrimination Information and Replica Dynamics
SO ENTROPY
LA English
DT Article
DE replicator equation; selection system; model reduction; discrimination
information; cross-entropy
ID MAXIMUM-ENTROPY PRODUCTION; GAME DYNAMICS; SELECTION; THEOREM
AB Dynamics of many complex systems can be described by replicator equations (RE). Here we present an effective method for solving a wide class of RE based on reduction theorems for models of inhomogeneous communities. The solutions of the RE minimize the discrimination information of the initial and current distributions at each point of the system trajectory, not only at the equilibrium, under time-dependent constraints. Applications to inhomogeneous versions of some conceptual models of mathematical biology (logistic and Ricker models of populations and Volterra' models of communities) are given.
C1 NIH, Lockheed Martin MSD, Bethesda, MD 20894 USA.
RP Karev, GP (reprint author), NIH, Lockheed Martin MSD, 38A,Rm 5N511N,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM karev@ncbi.nlm.nih.gov
NR 19
TC 8
Z9 8
U1 0
U2 1
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1099-4300
J9 ENTROPY-SWITZ
JI Entropy
PD JUL
PY 2010
VL 12
IS 7
BP 1673
EP 1695
DI 10.3390/e12071673
PG 23
WC Physics, Multidisciplinary
SC Physics
GA 631LC
UT WOS:000280347300002
ER
PT J
AU Mace-Aime, G
Couve, S
Khassenov, B
Rosselli, F
Saparbaev, MK
AF Mace-Aime, Gaetane
Couve, Sophie
Khassenov, Bekbolat
Rosselli, Filippo
Saparbaev, Murat K.
TI The Fanconi Anemia Pathway Promotes DNA Glycosylase-Dependent Excision
of Interstrand DNA Crosslinks
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Review
DE psoralen; interstrand crosslinks; Fanconi anemia; oxidative DNA damage;
base excision repair; DNA glycosylase
ID INCISION REPAIR PATHWAY; CELL NUCLEAR ANTIGEN; CHROMOSOMAL-ABERRATIONS;
IONIZING-RADIATION; ENDONUCLEASE-VIII; OXIDATIVE DAMAGE;
MAMMALIAN-CELLS; STRAND BREAKS; MAJOR ROLES; NEIL1 DNA
AB Fanconi anemia (FA) is a recessive cancer prone syndrome featuring bone marrow failure and hypersensitivity to DNA interstrand crosslinks (ICLs) and, to a milder extension, to ionizing radiation and oxidative stress. Recently, we reported that human oxidative DNA glycosylase, NEIL1 excises with high efficiency the unhooked crosslinked oligomer within three-stranded DNA repair intermediate induced by photoactivated psoralen exposure. Complete reconstitution of repair of the ICL within a three-stranded DNA structure shows that it is processed in the short-patch base excision repair (BER) pathway. To examine whether the DNA damage hypersensitivity in FA cells follows impaired BER activities, we measured DNA glycosylase and AP endonuclease activities in cell-free extracts from wild-type, FA, and FA-corrected cells. We showed that immortalized lymphoid cells of FA complementation Groups A, C, and D and from control cells from normal donors contain similar BER activities. Intriguingly, the cellular level of NEIL1 protein strongly depends on the intact FA pathway suggesting that the hypersensitivity of FA cells to ICLs may, at least in part, arise from downregulation or degradation of NEIL1. Consistent with this result, plasmid-based expression of the FLAG-tagged NEIL1 protein partially complements the hypersensitivity FA cells to the crosslinking agents exposures, suggesting that NEIL1 specifically complements impaired capability of FA cells to repair ICLs and oxidative DNA damage. These findings shed light to how the FA pathway may regulate DNA repair proteins and bring explanation for the long-time disputed problem of the oxidative stress sensitive phenotype of FA cells. Environ. Mol. Mutagen. 51:508-519, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Mace-Aime, Gaetane; Rosselli, Filippo] Univ Paris 11, CNRS, Grp UMR8200, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France.
[Couve, Sophie; Saparbaev, Murat K.] Univ Paris 11, CNRS, Grp UMR 8126, Reparat ADN,Inst Cancerol Gustave Roussy, F-94805 Villejuif, France.
[Khassenov, Bekbolat] Natl Biotechnol Ctr, Dept Genet & Biochem Microorganisms, Astana, Kazakhstan.
RP Rosselli, F (reprint author), Univ Paris 11, CNRS, Grp UMR8200, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France.
EM rosselli@igr.fr; smurat@igr.fr
RI Saparbaev, Murat/N-3225-2015;
OI Saparbaev, Murat/0000-0002-4630-1074; Khassenov,
Bekbolat/0000-0003-4572-948X
FU Fondation Pour la Recherche Medicale [EQUIPES FRM 2007]; FP6 Euroatom
Grant RISC-RAD [FI6R-CT-2003-508842]; CNRS GRDE 182: Institut National
du Cancer (INCa); Association Pour la Recherche sur le Cancer (ARC);
Electricite de France (EDF); National Center for Biotechnology of the
Republic of Kazakhstan; La Ligue Contre le Cancer "Equipe Labellisee
2006 et 2009"; INCA; C.N.R.S; Science Committee of the Ministry of
Education and Science of the Republic of Kazakhstan
FX Grant sponsors: Fondation Pour la Recherche Medicale; Grant Number:
EQUIPES FRM 2007; FP6 Euroatom Grant RISC-RAD; Grant Numbers:
FI6R-CT-2003-508842, CNRS GRDE 182: Institut National du Cancer (INCa),
Association Pour la Recherche sur le Cancer (ARC), Electricite de France
(EDF), National Center for Biotechnology of the Republic of Kazakhstan,
La Ligue Contre le Cancer "Equipe Labellisee 2006 et 2009".; The authors
thank Dr. J. Laval, Dr. J.-C. Ehrhart, and Dr. V. Ogryzko for helpful
discussions. They also thank Hiroshi Ide (Hiroshima University, Japan)
and Haruhiko Sugimura (University School of Medicine, Hamamatsu, Japan)
for plasmid constructs, and Grigory Dianov (MRC, Harwell, Oxfordshire,
UK) and Dmitry Zharkov (ICBFM, Novosibirsk, Russia) for the recombinant
proteins. S.C.. BK., and M.K.S. designed and performed all of the
biochemical and mass spectrometry experiments. G.M.-A. and F.R. designed
and performed all of the cell culture. Western blot, siRNA, and survival
experiments. M.K.S. wrote the manuscript. All authors discussed the
results and contributed to the manuscript. G.M.-A.. S.C., and B.K. were
supported by postdoctoral fellowships from the INCA. C.N.R.S., and
Science Committee of the Ministry of Education and Science of the
Republic of Kazakhstan, respectively.
NR 66
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Z9 12
U1 1
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUL
PY 2010
VL 51
IS 6
SI SI
BP 508
EP 519
DI 10.1002/em.20548
PG 12
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 627DI
UT WOS:000280019000004
PM 20120016
ER
PT J
AU Ladou, J
Castleman, B
Frank, A
Gochfeld, M
Greenberg, M
Huff, J
Joshi, TK
Landrigan, PJ
Lemen, R
Myers, J
Soffritti, M
Soskolne, CL
Takahashi, K
Teitelbaum, D
Terracini, B
Watterson, A
AF Ladou, Joseph
Castleman, Barry
Frank, Arthur
Gochfeld, Michael
Greenberg, Morris
Huff, James
Joshi, Tushar Kant
Landrigan, Philip J.
Lemen, Richard
Myers, Jonny
Soffritti, Morando
Soskolne, Colin L.
Takahashi, Ken
Teitelbaum, Daniel
Terracini, Benedetto
Watterson, Andrew
TI The Case for a Global Ban on Asbestos
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE asbestos; asbestos cancer pandemic; asbestos-related diseases; ban;
cancer; chrysotile; controlled use; disinformation; mesothelioma;
product defense
ID CHRYSOTILE ASBESTOS; MALIGNANT MESOTHELIOMA; PUBLIC-HEALTH;
INTERNATIONAL-ORGANIZATIONS; OCCUPATIONAL-EXPOSURE; CANCER-MORTALITY;
LUNG-CANCER; RISK; DISEASE; ASSOCIATION
AB BACKGROUND: All forms of asbestos are now banned in 52 countries. Safer products have replaced many materials that once were made with it. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products, and in those that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos is often exempted from the ban. In fact, chrysotile has accounted for > 95% of all the asbestos used globally.
OBJECTIVE: We examined and evaluated the literature used to support the exemption of chrysotile asbestos from the ban and how its exemption reflects the political and economic influence of the asbestos mining and manufacturing industry.
DISCUSSION: All forms of asbestos, including chrysotile, are proven human carcinogens. All forms cause malignant mesothelioma and lung and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers. No exposure to asbestos is without risk. Illnesses and deaths from asbestos exposure are entirely preventable.
CONCLUSIONS: All countries of the world have an obligation to their citizens to join in the international endeavor to ban the mining, manufacture, and use of all forms of asbestos. An international ban is urgently needed. There is no medical or scientific basis to exempt chrysotile from the worldwide ban of asbestos.
C1 [Ladou, Joseph] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
[Castleman, Barry] Environm Consultant, Garrett Pk, MD USA.
[Frank, Arthur] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
[Gochfeld, Michael] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, Piscataway, NJ 08854 USA.
[Huff, James] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Joshi, Tushar Kant] Ctr Occupat & Environm Hlth, New Delhi, India.
[Landrigan, Philip J.] Mt Sinai Sch Med, Global Hlth Program, New York, NY USA.
[Lemen, Richard] NIOSH, Canton, GA USA.
[Myers, Jonny] Univ Cape Town, Ctr Occupat & Environm Hlth Res, ZA-7925 Cape Town, South Africa.
[Soffritti, Morando] European Fdn Oncol & Environm Sci, Bologna, Italy.
[Soskolne, Colin L.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada.
[Takahashi, Ken] Univ Occupat & Environm Hlth, Dept Epidemiol, Kitakyushu, Fukuoka 807, Japan.
[Teitelbaum, Daniel] Univ Colorado, Sch Publ Hlth, Denver, CO 80202 USA.
[Terracini, Benedetto] Univ Turin, Ctr Canc Prevent, Turin, Italy.
[Watterson, Andrew] Univ Stirling, Occupat & Environm Hlth Res Grp, Stirling FK9 4LA, Scotland.
RP Ladou, J (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
EM joeladou@aol.com
NR 98
TC 53
Z9 55
U1 4
U2 19
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2010
VL 118
IS 7
BP 897
EP 901
DI 10.1289/ehp.1002285
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 619MX
UT WOS:000279435400015
PM 20601329
ER
PT J
AU Van Hee, VC
Adar, SD
Szpiro, AA
Barr, RG
Roux, AD
Bluemke, DA
Sheppard, L
Gill, EA
Bahrami, H
Wassel, C
Sale, MM
Siscovick, DS
Rotter, JI
Rich, SS
Kaufman, JD
AF Van Hee, Victor C.
Adar, Sara D.
Szpiro, Adam A.
Barr, R. Graham
Roux, Ana Diez
Bluemke, David A.
Sheppard, Lianne
Gill, Edward A.
Bahrami, Hossein
Wassel, Christina
Sale, Michele M.
Siscovick, David S.
Rotter, Jerome I.
Rich, Stephen S.
Kaufman, Joel D.
TI Common Genetic Variation, Residential Proximity to Traffic Exposure, and
Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE AGTR1; ALOX15; cardiac structure; cardiac MRI; gene-environment
interactions; left ventricular mass; traffic; air pollution
ID PARTICULATE AIR-POLLUTION; HEART-RATE-VARIABILITY; LONG-TERM EXPOSURE;
PARTICLE CONCENTRATIONS; ENVIRONMENT INTERACTION; LINKAGE
DISEQUILIBRIUM; CARDIOVASCULAR EVENTS; SPATIAL VARIABILITY; MISSING
VALUES; ASSOCIATION
AB BACKGROUND: Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways.
OBJECTIVE: We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM.
METHODS: This was a cross-sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders.
RESULTS: After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9-10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity.
CONCLUSIONS: Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways.
C1 [Van Hee, Victor C.] Univ Washington, Harborview Med Ctr, Occupat & Environm Med Program, Dept Environm & Occupat Hlth Sci, Seattle, WA 98104 USA.
[Van Hee, Victor C.; Gill, Edward A.; Siscovick, David S.; Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA 98104 USA.
[Adar, Sara D.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA.
[Szpiro, Adam A.; Sheppard, Lianne] Univ Washington, Dept Biostat, Seattle, WA 98104 USA.
[Barr, R. Graham] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
[Barr, R. Graham] Columbia Univ, Dept Epidemiol, Med Ctr, New York, NY USA.
[Roux, Ana Diez] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Bluemke, David A.] NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Bahrami, Hossein] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Bahrami, Hossein] Johns Hopkins Sch Med, Dept Cardiol, Baltimore, MD USA.
[Wassel, Christina] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA.
[Sale, Michele M.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Dept Med Genet, Los Angeles, CA 90048 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
RP Van Hee, VC (reprint author), Univ Washington, Harborview Med Ctr, Occupat & Environm Med Program, Dept Environm & Occupat Hlth Sci, Box 359739,325 9th Ave, Seattle, WA 98104 USA.
EM vvanhee@u.washington.edu
RI Kaufman, Joel/B-5761-2008; Adar, Sara/L-2278-2016;
OI Kaufman, Joel/0000-0003-4174-9037; Adar, Sara/0000-0001-8383-485X;
Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165,
N01-HC-95169, R01 HL077612, HL070151, HL071205, HL071251-52,
HL071258-59, T32HL07902]; U.S. Environmental Protection Agency
[RD831697]; National Institute of Environmental Health Sciences
[P50ES015915, P30ES07033, K24ES013195]
FX This study was supported by National Heart, Lung, and Blood Institute
contracts N01-HC-95159 through N01-HC-95165, N01-HC-95169, R01 HL077612,
HL070151, HL071205, HL071251-52, HL071258-59, and T32HL07902; U.S.
Environmental Protection Agency Science to Achieve Results grant
RD831697; and National Institute of Environmental Health Sciences grants
P50ES015915, P30ES07033, and K24ES013195.
NR 61
TC 19
Z9 19
U1 0
U2 10
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2010
VL 118
IS 7
BP 962
EP 969
DI 10.1289/ehp.0901535
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 619MX
UT WOS:000279435400025
PM 20308035
ER
PT J
AU Ranguelova, K
Bonini, MG
Mason, RP
AF Ranguelova, Kalina
Bonini, Marcelo G.
Mason, Ronald P.
TI (Bi)sulfite Oxidation by Copper,Zinc-Superoxide Dismutase:
Sulfite-Derived, Radical-Initiated Protein Radical Formation
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE ESR spin trapping; immuno-spin trapping; sulfite radicals; sulfite
toxicity
ID CU,ZN SUPEROXIDE-DISMUTASE; CU,ZN-SUPEROXIDE DISMUTASE;
HORSERADISH-PEROXIDASE; CATALYZED OXIDATION; HYDROGEN-PEROXIDE;
ELECTRON-TRANSFER; AQUEOUS-SOLUTION; SULFUR-DIOXIDE; ANION; AUTOXIDATION
AB BACKGROUND: Sulfur dioxide, formed during the combustion of fossil fuels, is a major air pollutant near large cities. Its two ionized forms in aqueous solution, sulfite and (bi)sulfite, are widely used as preservatives and anti-oxidants to prevent food and beverage spoilage. (Bi)sulfite can be oxidized by peroxidases to form the very reactive sulfur trioxide anion radical ((center dot)SO(3)(-)). This free radical further reacts with oxygen to form the peroxy-monosulfate anion radical ((-)O(3)SOO(center dot)) and sulfate anion radical (SO(4)(center dot-)).
OBJECTIVE: To explore the critical role of these radical intermediates in further oxidizing biomolecules, we examined the ability of copper, zinc- superoxide dismutase (Cu,Zn-SOD) to initiate this radical chain reaction, using human serum albumin (HSA) as a model target.
METHODS: We used electron paramagnetic resonance, optical spectroscopy, oxygen uptake, and immuno-spin trapping to study the protein oxidations driven by sulfite-derived radicals.
RESULTS: We found that when Cu, Zn-SOD reacted with (bi)sulfite, (center dot)SO(3)(-) was produced, with the concomitant reduction of SOD-Cu(II) to SOD-Cu(I). Further, we demonstrated that sulfite oxidation mediated by Cu, Zn-SOD induced the formation of radical-derived 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin-trapped HSA radicals.
CONCLUSIONS: The present study suggests that protein oxidative damage resulting from (bi) sulfite oxidation promoted by Cu, Zn-SOD could be involved in oxidative damage and tissue injury in (bi)sulfite-exacerbated allergic reactions.
C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Med, Chicago, IL USA.
RP Ranguelova, K (reprint author), NIEHS, Pharmacol Lab, NIH, Dept Hlth & Human Serv, F0-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM RanguelovaK@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 39
TC 17
Z9 19
U1 6
U2 28
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2010
VL 118
IS 7
BP 970
EP 975
DI 10.1289/ehp.0901533
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 619MX
UT WOS:000279435400026
PM 20348042
ER
PT J
AU Vinikoor, LC
Larson, TC
Bateson, TF
Birnbaum, L
AF Vinikoor, Lisa C.
Larson, Theodore C.
Bateson, Thomas F.
Birnbaum, Linda
TI Exposure to Asbestos-Containing Vermiculite Ore and Respiratory Symptoms
among Individuals Who Were Children While the Mine Was Active in Libby,
Montana
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE asbestos; children; Libby; Montana; respiratory symptoms; spirometry;
vermiculite ore
ID AIR-POLLUTION; ENVIRONMENTAL EXPOSURE; PLEURAL MESOTHELIOMA; TREMOLITE
ACTINOLITE; MORTALITY; CHILDHOOD; MORBIDITY; ABNORMALITIES; POPULATION;
DISEASE
AB BACKGROUND: Libby, Montana, was home to the largest vermiculite ore mine in the United States. The processing, use, and transport of the ore, which was contaminated with amphibole asbestos, led to generalized contamination of the community. The mine closed in 1990.
OBJECTIVES: We examined the prevalence of respiratory symptoms in 2000-2001 and their association with history of vermiculite exposure among people who were <= 18 years of age when the mine closed.
METHODS: Information on respiratory symptoms and exposure history was collected by questionnaire in 2000-2001, at which time participants were 10-29 years old. Logistic regression was used to model the associations between exposures and outcomes adjusted for age, sex, and tobacco smoke exposure.
RESULTS: Of the 1,003 individuals included in the study, 10.8% reported usually having a cough, 14.5% reported experiencing shortness of breath when walking up a slight hill or hurrying on level ground, and 5.9% reported having coughed up bloody phlegm in the past year. These respiratory symptoms were positively associated with frequently handling vermiculite insulation compared with never handling vermiculite insulation. We found no association between vermiculite insulation in the house and respiratory symptoms. Respiratory symptoms were associated with other vermiculite exposures as well, and the number and frequency of these activities showed a positive trend with usually having a cough. We found no association between any of the activities and abnormal spirometry.
CONCLUSIONS: These data suggest that residents of Libby, Montana, who were children when the mine closed experienced some respiratory symptoms associated with asbestos-contaminated vermiculite exposure.
C1 [Vinikoor, Lisa C.] US EPA, Res Triangle Pk, NC 27711 USA.
[Larson, Theodore C.] Agcy Tox Subst & Dis Registry, Atlanta, GA USA.
[Bateson, Thomas F.] US EPA, Washington, DC 20460 USA.
[Birnbaum, Linda] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Vinikoor, LC (reprint author), US EPA, MD B243-01,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA.
EM vinikoor.lisa@epa.gov
NR 30
TC 21
Z9 22
U1 5
U2 17
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2010
VL 118
IS 7
BP 1033
EP 1038
DI 10.1289/ehp.0901680
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 619MX
UT WOS:000279435400037
PM 20332072
ER
PT J
AU Birnbaum, LS
Schroeder, JC
Tilson, HA
AF Birnbaum, Linda S.
Schroeder, Jane C.
Tilson, Hugh A.
TI A Repeat Call for the Banning of Asbestos
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID MESOTHELIOMA
C1 [Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov; schroederjc@niehs.nih.gov;
tilsonha@niehs.nih.gov
NR 18
TC 2
Z9 2
U1 0
U2 1
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2010
VL 118
IS 7
BP A280
EP A281
DI 10.1289/ehp.1002419
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 619MX
UT WOS:000279435400001
PM 20601328
ER
PT J
AU Basso, O
Wilcox, A
AF Basso, Olga
Wilcox, Allen
TI Mortality Risk Among Preterm Babies Immaturity Versus Underlying
Pathology
SO EPIDEMIOLOGY
LA English
DT Article
ID WEIGHT-SPECIFIC MORTALITY; FOR-GESTATIONAL-AGE; BIRTH-WEIGHT;
UNITED-STATES; INFLAMMATORY RESPONSE; PERINATAL-MORTALITY; TEMPORAL
TRENDS; FETAL-GROWTH; OUTCOMES; INFANTS
AB Background: Deaths among preterm births are presumably due to both immaturity and the conditions that cause preterm birth. Their relative contributions are unknown.
Methods: Using US birth certificates (1995-2002), we estimated what portion of preterm neonatal mortality may be attributable to immaturity alone. Twins have elevated mortality, yet they usually have lower mortality than singletons at most preterm weeks. Twinning itself is a cause of early birth. Thus, at any given preterm week, singletons are more likely than twins to have pathologic causes of preterm delivery. If any such cause is associated with a mortality risk higher than that conferred by twinning, it is possible for singletons to have higher mortality than twins at some preterm weeks. Thus, mortality of twins at those weeks comes closer to describing the risk due to immaturity itself. To exclude high-risk babies, we focused on singletons and twins least likely to have suffered fetal growth disruptions (ie, those with "optimal" birth weight). At each gestational week from 24 to 36, we identified (for twins and singletons separately) the 500-gram weight category with the lowest neonatal mortality, and selected the lower of the 2 mortality rates.
Results: Using the above as our best estimates of mortality due to immaturity alone, we calculated that about half the mortality of singleton preterm babies was due to the pathologies that cause early delivery.
Conclusions: Factors that cause preterm birth apparently contribute a large proportion of preterm mortality. If so, the prevention of preterm mortality requires more than the postponement of delivery.
C1 [Basso, Olga; Wilcox, Allen] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Basso, O (reprint author), McGill Univ, Dept Obstet & Gynecol, Royal Victoria Hosp, 687 Pine Ave W,Room F9-05, Montreal, PQ H3A 1A1, Canada.
EM olga.basso@mcgill.ca
RI Basso, Olga/E-5384-2010;
OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311
FU NIH, National Institute of Environmental Health Sciences [Z01 ES044003]
FX Supported by the Intramural program of the NIH, National Institute of
Environmental Health Sciences (Z01 ES044003).
NR 40
TC 31
Z9 31
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2010
VL 21
IS 4
BP 521
EP 527
DI 10.1097/EDE.0b013e3181debe5e
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 614EQ
UT WOS:000279038600015
PM 20407380
ER
PT J
AU Albert, PS
Harel, O
Perkins, N
Browne, R
AF Albert, Paul S.
Harel, Ofer
Perkins, Neil
Browne, Richard
TI Use of Multiple Assays Subject to Detection Limits With Regression
Modeling in Assessing the Relationship Between Exposure and Outcome
SO EPIDEMIOLOGY
LA English
DT Article
AB Background: The goal of many studies in environmental epidemiology is to assess the relationship between chemical exposure and disease outcome. Often various assays can be used to measure a particular environmental exposure, with some assays being more invasive or expensive than others.
Methods: We consider the situation in which 2 assays can be used to measure an environmental exposure. The first assay has measurement error and is subject to a lower detection limit (LOD), and the second assay has less measurement error and is not subject to a lower LOD. In this situation, the first assay is less invasive or less expensive and is measured in all study participants, whereas the second assay is more invasive or more expensive and is only measured in a subset of individuals. We develop a flexible class of regression models that incorporates both sets of assay measurements and allows for continuous or binary outcomes. We explore different design strategies for selecting the subset of patients in whom to measure the second assay. One design strategy is to measure the second more invasive or expensive assay only when the first assay is below LOD. We compare these designs with a simple design in which the second assay is measured in a random subset of patients without regard to the results of the first assay.
Results: We develop estimation approaches for these regression models. We demonstrate through simulations that there are efficiency advantages of measuring the second assay in at least a fraction of cases in which the first assay is above LOD. We illustrate the methodology by using data from a study examining the effect of environmental polychlorinated biphenyl exposure on the risk of endometriosis.
Conclusion: The proposed methodology has good statistical properties and will be a useful methodological technique for studying the effect of exposure on outcome when exposure assays are subject to LOD.
C1 [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20906 USA.
[Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Perkins, Neil] Eunice Kennedy Shriver Natl Inst Child Hlth, Epidemiol Branch, Div Epidemiol Stat & Prevent, Rockville, MD USA.
[Browne, Richard] SUNY Buffalo, Dept Clin Lab Sci, Buffalo, NY 14260 USA.
RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B05F, Bethesda, MD 20906 USA.
EM albertp@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733
FU Long Range Initiative of the American Chemistry Council; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institutes of Health
FX Supported partially by the Long Range Initiative of the American
Chemistry Council and funding from the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health.
NR 8
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2010
VL 21
SU 4
BP S35
EP S43
DI 10.1097/EDE.0b013e3181ce9eed
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 614FB
UT WOS:000279039700006
PM 20386105
ER
PT J
AU Browne, RW
Whitcomb, BW
AF Browne, Richard W.
Whitcomb, Brian W.
TI Procedures for Determination of Detection Limits Application to
High-performance Liquid Chromatography Analysis of Fat-soluble Vitamins
in Human Serum
SO EPIDEMIOLOGY
LA English
DT Article
ID PARTLY NONPARAMETRIC APPROACH; BIOLOGICAL VARIATION; ASSAYS; ERROR; HPLC
AB Background: Problems in the analysis of laboratory data commonly arise in epidemiologic studies in which biomarkers subject to lower detection thresholds are used. Various thresholds exist including limit of detection (LOD), limit of quantification (LOQ), and limit of blank (LOB). Choosing appropriate strategies for dealing with data affected by such limits relies on proper understanding of the nature of the detection limit and its determination. In this paper, we demonstrate experimental and statistical procedures generally used for estimating different detection limits according to standard procedures in the context of analysis of fat-soluble vitamins and micronutrients in human serum.
Methods: Fat-soluble vitamins and micronutrients were analyzed by high-performance liquid chromatography with diode array detection. A simulated serum matrix blank was repeatedly analyzed for determination of LOB parametrically by using the observed blank distribution as well as nonparametrically by using ranks. The LOD was determined by combining information regarding the LOB with data from repeated analysis of standard reference materials (SRMs), diluted to low levels; from LOB to 2-3 times LOB. The LOQ was determined experimentally by plotting the observed relative standard deviation (RSD) of SRM replicates compared with the concentration, where the LOQ is the concentration at an RSD of 20%.
Results: Experimental approaches and example statistical procedures are given for determination of LOB, LOD, and LOQ. These quantities are reported for each measured analyte.
Conclusion: For many analyses, there is considerable information available below the LOQ. Epidemiologic studies must understand the nature of these detection limits and how they have been estimated for appropriate treatment of affected data.
C1 [Browne, Richard W.] SUNY Buffalo, Dept Biotech, Buffalo, NY 14214 USA.
[Browne, Richard W.] SUNY Buffalo, Clin Sci Lab, Buffalo, NY 14214 USA.
[Whitcomb, Brian W.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Whitcomb, Brian W.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA.
RP Browne, RW (reprint author), SUNY Buffalo, Dept Biotech, 26 Cary Hall, Buffalo, NY 14214 USA.
EM rwbrowne@buffalo.edu
FU American Chemistry Council; National Institute of Child Health and Human
Development [ADB-N01-HD-4-3394]
FX Supported in part by the American Chemistry Council and by an intramural
contract with the National Institute of Child Health and Human
Development (Contract No. ADB-N01-HD-4-3394).
NR 15
TC 12
Z9 12
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2010
VL 21
SU 4
BP S4
EP S9
DI 10.1097/EDE.0b013e3181ce9a61
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 614FB
UT WOS:000279039700002
PM 20220523
ER
PT J
AU Kang, L
Vexler, A
Tian, LL
Cooney, M
Louis, GMB
AF Kang, Le
Vexler, Albert
Tian, Lili
Cooney, Maureen
Louis, Germaine M. Buck
TI Empirical and Parametric Likelihood Interval Estimation for Populations
With Many Zero Values Application for Assessing Environmental Chemical
Concentrations and Reproductive Health
SO EPIDEMIOLOGY
LA English
DT Article
ID CONFIDENCE-INTERVALS; LOGNORMAL DATA; ENDOMETRIOSIS; EXPOSURE; SUBJECT;
SAMPLES; MODELS; LIMIT
AB Background: Understanding the health effects associated with environmental chemicals is challenging when individuals have concentrations at or below the laboratory limits of detection as well as when the values may round to zero or are presented in the form of 0 to substitute for missing values, which may result in many zeros in the database. Comparison of mean concentrations between individuals with and without disease necessitates estimation procedures that allow for data with many zero values. The main aim of this article is to propose and examine parametric and distribution-free methods for comparing data sets containing many zero observations. An important application of this approach is related to assessing environmental chemical concentrations and reproductive health.
Methods: We extended the empirical likelihood technique for estimating confidence intervals (CIs) in data sets with many zeros. We examined the proposed empirical likelihood interval estimations via a broad Monte Carlo study that compares the proposed method with parametric techniques. Certain characteristics of Monte Carlo simulations were chosen to be close to parameters of the real data set. We applied the method to a cohort study comprising 84 women aged 18-40 years who had undergone laparoscopy between 1999 and 2000 in whom serum concentrations of 2 organochlorine pesticides-Aldrin and beta-Benzene hexachloride (beta-BHC) were measured using gas chromatography with electron capture.
Results: When applied to the cohort study, the method produced efficient 95% CIs, allowing for the comparison of mean serum Aldrin concentrations for women with and without endometriosis (0.000338, 0.003561) and (0.000803, 0.004211), respectively. Mean beta-BHC concentrations also could be compared (0.000493, 0.005869) and (0.000680, 0.003807) based on individuals with and without the disease, respectively. Differences in mean concentrations for Aldrin and beta-BHC could be estimated (-0.001563, 0.003025) and (-0.003522, 0.002890), respectively.
Conclusions: We found the empirical likelihood method for estimating CIs robust when data sets contain many zeros. In so doing, mean concentrations of Aldrin or beta-BHC did not differ by endometriosis diagnosis.
C1 [Kang, Le; Vexler, Albert; Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
[Cooney, Maureen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA.
RP Kang, L (reprint author), SUNY Buffalo, Dept Biostat, 249 Farber Hall,3435 Main St, Buffalo, NY 14214 USA.
EM lekang@buffalo.edu
RI Kang, Le/G-6935-2012;
OI Buck Louis, Germaine/0000-0002-1774-4490
FU American Chemistry Council; Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX Supported in part by the American Chemistry Council and the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development.
NR 15
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2010
VL 21
SU 4
BP S58
EP S63
DI 10.1097/EDE.0b013e3181d7eb68
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 614FB
UT WOS:000279039700009
PM 21422967
ER
PT J
AU Nie, L
Chu, HT
Liu, CL
Cole, SR
Vexler, A
Schisterman, EF
AF Nie, Lei
Chu, Haitao
Liu, Chenglong
Cole, Stephen R.
Vexler, Albert
Schisterman, Enrique F.
TI Linear Regression With an Independent Variable Subject to a Detection
Limit
SO EPIDEMIOLOGY
LA English
DT Article
ID MEASUREMENT ERROR; MODELS
AB Background: Linear regression with a left-censored independent variable X due to limit of detection (LOD) was recently considered by 2 groups of researchers: Richardson and Ciampi (Am J Epidemiol. 2003; 157: 355-363), and Schisterman et al (Am J Epidemiol. 2006; 163: 374-383).
Methods: Both groups obtained consistent estimators for the regression slopes by replacing left-censored X with a constant, that is, the expectation of X given X below LOD E(X vertical bar X= 1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. Published by Elsevier Ltd.
C1 [Ren, J. S.; Freedman, N. D.; Kamangar, F.; Dawsey, S. M.; Schatzkin, A.; Abnet, C. C.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Hollenbeck, A. R.] Knowledge Management, AARP, Washington, DC USA.
RP Abnet, CC (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA.
EM abnetc@mail.nih.gov
RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015
OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health. Cancer incidence data from
Georgia were collected by the Georgia Center for Cancer Statistics,
Department of Epidemiology, Rollins School of Public Health, Emory
University. Cancer incidence data from California were collected by the
California Department of Health Services, Cancer Surveillance Section.
Cancer incidence data from Michigan were collected by the Michigan
Cancer Surveillance Program, Community Health Administration, State of
Michigan. The Florida cancer incidence data used in this report were
collected by the Florida Cancer Data System under contract to the
Department of Health (DOH). The views expressed herein are solely those
of the authors and do not necessarily reflect those of the contractor or
DOH. Cancer incidence data from Louisiana were collected by the
Louisiana Tumor Registry, Louisiana State University Medical Center in
New Orleans. Cancer incidence data from New Jersey were collected by the
New Jersey State Cancer Registry, Cancer Epidemiology Services, New
Jersey State Department of Health and Senior Services. Cancer incidence
data from North Carolina were collected by the North Carolina Central
Cancer Registry. Cancer incidence data from Pennsylvania were supplied
by the Division of Health Statistics and Research, Pennsylvania
Department of Health, Harrisburg, Pennsylvania. The Pennsylvania
Department of Health specifically disclaims responsibility for any
analyses, interpretations or conclusions. Cancer incidence data from
Arizona were collected by the Arizona Cancer Registry, from Nevada by
the Nevada Central Cancer registry, and from Texas by the Texas Cancer
Registry.; We appreciate all the participants in the NIH-AARP Diet and
Health Study for their outstanding cooperation.
NR 47
TC 39
Z9 40
U1 1
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD JUL
PY 2010
VL 46
IS 10
BP 1873
EP 1881
DI 10.1016/j.ejca.2010.03.025
PG 9
WC Oncology
SC Oncology
GA 627JO
UT WOS:000280035500029
PM 20395127
ER
PT J
AU Heyerdahl, SL
Rozenberg, J
Jamtgaard, L
Rishi, V
Varticovski, L
Akah, K
Scudiero, D
Shoemaker, RH
Karpova, TS
Day, RN
McNally, JG
Vinson, C
AF Heyerdahl, Sarah L.
Rozenberg, Julian
Jamtgaard, Louis
Rishi, Vikas
Varticovski, Lyuba
Akah, Kelly
Scudiero, Dominic
Shoemaker, Robert H.
Karpova, Tatiana S.
Day, Richard N.
McNally, James G.
Vinson, Charles
TI The arylstibonic acid compound NSC13746 disrupts B-ZIP binding to DNA in
living cells
SO EUROPEAN JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE B-ZIP domain; VBP; FRAP; arylstibonic acid; antimony; DNA binding
ID RED FLUORESCENT PROTEIN; TRANSCRIPTION FACTORS; LEUCINE-ZIPPER;
LOCALIZATION; BZIP; TRANSLOCATION; ACTIVATION; CHROMATIN; LEUKEMIA; JUN
AB The inhibition of DNA binding of basic leucine zipper (B-ZIP) transcription factors is a clinically relevant molecular target. Our laboratory has previously reported two methods of inhibiting B-ZIP DNA binding in solution: 1) an arylstibonic acid compound that binds to the basic region, stabilizes the B-ZIP dimer, and prevents B-ZIP DNA binding and 2) dominant negative proteins, termed A-ZIPs, that heterodimerize with B-ZIP domains in a leucine zipper-dependent manner. To determine if these two agents also inhibit DNA binding in live cells, GFP-tagged B-ZIP domains and mCherry-tagged A-ZIP domains were transfected into NIH3T3 cells to assess protein localization and Fluorescence Recovery After nuclear Photobleaching (FRAP). FRAP, showed that all six GFP-B-ZIP domains examined recovered faster in the nucleus in the presence of drug that we interpret represents an inhibition of DNA binding. Faster recovery in the presence of the A-ZIP was leucine zipper dependent. The arylstibonic also induced a cytoplasmic localization of all B-ZIP domains while the A-ZIPs induced a leucine zipper-dependent cytoplasmic localization. Thus, the change in cellular localization of B-ZIP domains could be used as a high-throughput assay for inhibitors of B-ZIP DNA binding. Additionally, the arylstibonic acid compound was cytostatic in clear cell sarcoma cells, which express a chimera between the B-ZIP domain of ATF-1 and N-terminal activation domain of EWS but not in K562 cells that express a non-B-ZIP containing chimeric protein BCR-ABL. These studies suggest that arylstibonic acid compounds or other small molecules capable of inhibiting B-ZIP DNA binding could be valuable anticancer agents. Published by Elsevier GmbH.
C1 [Heyerdahl, Sarah L.; Rozenberg, Julian; Jamtgaard, Louis; Rishi, Vikas; Akah, Kelly; Vinson, Charles] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Scudiero, Dominic] Sci Applicat Int Corp, Frederick, MD 21702 USA.
[Shoemaker, Robert H.] NCI, Dev Therapeut Program, DCTD, Frederick, MD 21702 USA.
[Karpova, Tatiana S.; McNally, James G.] NCI, Imaging Core Facil, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Varticovski, Lyuba] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA.
[Day, Richard N.] Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA 22908 USA.
RP Vinson, C (reprint author), NCI, Metab Branch, NIH, Bldg 37,Room 3128, Bethesda, MD 20892 USA.
EM Vinsonc@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400]
FX We thank Dr. Diana Stavreva for the GFP-GR plasmid and Alan Epstein,
Department of Pathology, USC Keck School of Medicine for the EWS-ATF1
cell line. This project has been funded in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract N01-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. government.
This research was conducted in partial fulfillment of the Johns Hopkins
University/National Cancer Institute, Center for Cancer Research degree
in Molecular Targets and Drug Discovery Technologies (Heyerdahl, SL).
NR 37
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-9335
J9 EUR J CELL BIOL
JI Eur. J. Cell Biol.
PD JUL
PY 2010
VL 89
IS 7
BP 564
EP 573
DI 10.1016/j.ejcb.2009.11.029
PG 10
WC Cell Biology
SC Cell Biology
GA 609FA
UT WOS:000278639900008
PM 20362353
ER
PT J
AU Valent, P
Akin, C
Sperr, WR
Horny, HP
Metcalfe, DD
AF Valent, Peter
Akin, Cem
Sperr, Wolfgang R.
Horny, Hans-Peter
Metcalfe, Dean D.
TI Refinements in response criteria in systemic mastocytosis: reply to a
proposal
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Letter
C1 [Valent, Peter; Sperr, Wolfgang R.] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, A-1090 Vienna, Austria.
[Akin, Cem] Harvard Univ, Sch Med, Boston, MA USA.
[Horny, Hans-Peter] Inst Pathol Ansbach, Ansbach, Germany.
[Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Valent, P (reprint author), Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM peter.valent@meduniwien.ac.at
OI Akin, Cem/0000-0001-6301-4520
NR 5
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0902-4441
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD JUL
PY 2010
VL 85
IS 1
BP 88
EP 89
DI 10.1111/j.1600-0609.2010.01462.x
PG 2
WC Hematology
SC Hematology
GA 612RM
UT WOS:000278920100015
PM 20456489
ER
PT J
AU Schaubert, KL
Price, DA
Salkowitz, JR
Sewell, AK
Sidney, J
Asher, TE
Blondelle, SE
Adams, S
Marincola, FM
Joseph, A
Sette, A
Douek, DC
Ayyavoo, V
Storkus, W
Leung, MY
Ng, HL
Yang, OO
Goldstein, H
Wilson, DB
Kan-Mitchell, J
AF Schaubert, Keri L.
Price, David A.
Salkowitz, Janelle R.
Sewell, Andrew K.
Sidney, John
Asher, Tedi E.
Blondelle, Sylvie E.
Adams, Sharon
Marincola, Francesco M.
Joseph, Aviva
Sette, Alessandro
Douek, Daniel C.
Ayyavoo, Velpandi
Storkus, Walter
Leung, Ming-Ying
Ng, Hwee L.
Yang, Otto O.
Goldstein, Harris
Wilson, Darcy B.
Kan-Mitchell, June
TI Generation of robust CD8(+) T-cell responses against subdominant
epitopes in conserved regions of HIV-1 by repertoire mining with
mimotopes
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Agonist peptide; CD8(+) CTL; HIV vaccine; In vitro immunization
ID COMBINATORIAL PEPTIDE LIBRARIES; HLA-B; LYMPHOCYTE RESPONSES;
BINDING-AFFINITY; SIV INFECTION; VIRAL ESCAPE; ANTIGEN; VACCINE;
RECOGNITION; RECEPTOR
AB HLA-A*0201-restricted virus-specific CD8(+) CTL do not appear to control HIV effectively in vivo. To enhance the immunogenicity of a highly conserved subdominant epitope, TV9 (TLNAWVKVV, p24 Gag(19-27)), mimotopes were designed by screening a large combinatorial nonapeptide library with TV9-specific CTL primed in vitro from healthy donors. A mimic peptide with a low binding affinity to HLA-A*0201, TV9p6 (KINAWIKVV), was studied further. Parallel cultures of in vitro-primed CTL showed that TV9p6 consistently activated cross-reactive and equally functional CTL as measured by cytotoxicity, cytokine production and suppression of HIV replication in vitro. Comparison of TCRB gene usage between CTL primed from the same donors with TV9 or TV9p6 revealed a degree of clonal overlap in some cases and an example of a conserved TCRB sequence encoded distinctly at the nucleotide level between individuals (a "public" TCR); however, in the main, distinct clonotypes were recruited by each peptide antigen. These findings indicate that mimotopes can mobilize functional cross-reactive clonotypes that are less readily recruited from the naive T-cell pool by the corresponding WT epitope. Mimotope-induced repertoire diversification could potentially override subdominance under certain circumstances and enhance vaccine-induced responses to conserved but poorly immunogenic determinants within the HIV proteome.
C1 [Schaubert, Keri L.; Salkowitz, Janelle R.; Kan-Mitchell, June] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA.
[Schaubert, Keri L.; Salkowitz, Janelle R.; Kan-Mitchell, June] Univ Texas El Paso, Border Biomed Res Inst, El Paso, TX 79968 USA.
[Schaubert, Keri L.; Kan-Mitchell, June] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Price, David A.; Asher, Tedi E.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Price, David A.; Sewell, Andrew K.] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff, S Glam, Wales.
[Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA USA.
[Blondelle, Sylvie E.; Wilson, Darcy B.] Torrey Pines Inst Mol Studies, San Diego, CA USA.
[Blondelle, Sylvie E.; Wilson, Darcy B.] Mixture Sci Inc, San Diego, CA USA.
[Adams, Sharon; Marincola, Francesco M.] NIH, Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA.
[Joseph, Aviva; Goldstein, Harris] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Joseph, Aviva; Goldstein, Harris] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Ayyavoo, Velpandi] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Storkus, Walter] Univ Pittsburgh, Dept Immunol, Inst Canc, Pittsburgh, PA USA.
[Storkus, Walter] Univ Pittsburgh, Dept Dermatol, Inst Canc, Pittsburgh, PA 15260 USA.
[Leung, Ming-Ying] Univ Texas El Paso, Dept Math Sci, El Paso, TX 79968 USA.
[Ng, Hwee L.; Yang, Otto O.] Univ Calif Los Angeles, Ctr Hlth Sci, Dept Med, Los Angeles, CA 90024 USA.
[Ng, Hwee L.; Yang, Otto O.] Univ Calif Los Angeles, Ctr Hlth Sci, AIDS Inst, Los Angeles, CA 90024 USA.
RP Kan-Mitchell, J (reprint author), Univ Texas El Paso, Dept Biol Sci, Biol Sci Bldg 4-128,500 W Univ Ave, El Paso, TX 79968 USA.
EM jkanmitchell@utep.edu
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Storkus, Walter/0000-0001-8961-4444;
Sewell, Andrew/0000-0003-3194-3135
FU Michigan Life Sciences Corridor Program [1659]; NIH [R01-AI064069,
R01-AI77413]; NCRR [5G12RR008124]; AIDS and Infectious Disease Science
Center, NIH [R43DA021175, R44DA015212]
FX This study was supported by the Michigan Life Sciences Corridor Program
1659 (J. K.-M.), NIH R01-AI064069 and R01-AI77413 (J. K.-M.), and NCRR
5G12RR008124 (J. K.-M.). We acknowledge support to S. E. B. and D. B. W.
from the AIDS and Infectious Disease Science Center, NIH R43DA021175 (S.
E. B.) and NIH R44DA015212 (D. B. W.). D. A. P. is a Medical Research
Council (UK) Senior Clinical Fellow.
NR 49
TC 8
Z9 8
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUL
PY 2010
VL 40
IS 7
BP 1950
EP 1962
DI 10.1002/eji.200940079
PG 13
WC Immunology
SC Immunology
GA 629SS
UT WOS:000280220600025
PM 20432235
ER
PT J
AU Rosario, M
Bridgeman, A
Quakkelaar, ED
Quigley, MF
Hill, BJ
Knudsen, ML
Ammendola, V
Ljungberg, K
Borthwick, N
Im, EJ
McMichael, AJ
Drijfhout, JW
Greenaway, HY
Venturi, V
Douek, DC
Colloca, S
Liljestrom, P
Nicosia, A
Price, DA
Melief, CJM
Hanke, T
AF Rosario, Maximillian
Bridgeman, Anne
Quakkelaar, Esther D.
Quigley, Maire F.
Hill, Brenna J.
Knudsen, Maria L.
Ammendola, Virginia
Ljungberg, Karl
Borthwick, Nicola
Im, Eung-Jun
McMichael, Andrew J.
Drijfhout, Jan W.
Greenaway, Hui Yee
Venturi, Vanessa
Douek, Daniel C.
Colloca, Stefano
Liljestrom, Peter
Nicosia, Alfredo
Price, David A.
Melief, Cornelis J. M.
Hanke, Tomas
TI Long peptides induce polyfunctional T cells against conserved regions of
HIV-1 with superior breadth to single-gene vaccines in macaques
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE HIV vaccines; Macaques; Prime-boost; Synthetic long peptides; T cells
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CERVICAL-CANCER PATIENTS;
HEALTHY-VOLUNTEERS; SIV INFECTION; VIRAL LOAD; RESPONSES; CD8(+); DNA;
IMMUNOGENICITY; IMMUNITY
AB A novel T-cell vaccine strategy designed to deal with the enormity of HIV-1 variation is described and tested for the first time in macaques to inform and complement approaching clinical trials. T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most conserved regions of the HIV-1, proteome and thus both targets diverse clades in the population and reduces the chance of escape in infected individuals, was delivered using six different vaccine modalities: plasmid DNA (D), attenuated human (A) and chimpanzee (C) adenoviruses, modified vaccinia virus Ankara (M), synthetic long peptides, and Semliki Forest virus replicons. We confirmed that the initial DDDAM regimen, which mimics one of the clinical schedules (DDDCM), is highly immunogenic in macaques. Furthermore, adjuvanted synthetic long peptides divided into sub-pools and delivered into anatomically separate sites induced T-cell responses that were markedly broader than those elicited by traditional single-open-reading-frame genetic vaccines and increased by 30% the overall response magnitude compared with DDDAM. Thus, by improving both the HIV-1-derived immunogen and vector regimen/delivery, this approach could induce stronger, broader, and theoretically more protective T-cell responses than vaccines previously used in humans.
C1 [Rosario, Maximillian; Bridgeman, Anne; Borthwick, Nicola; Im, Eung-Jun; McMichael, Andrew J.; Hanke, Tomas] Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England.
[Quakkelaar, Esther D.; Drijfhout, Jan W.; Melief, Cornelis J. M.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands.
[Quigley, Maire F.; Hill, Brenna J.; Douek, Daniel C.; Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Knudsen, Maria L.; Ljungberg, Karl; Liljestrom, Peter] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Ammendola, Virginia; Colloca, Stefano; Nicosia, Alfredo] Okairos Srl, Rome, Italy.
[Greenaway, Hui Yee; Venturi, Vanessa] Univ New S Wales, Computat Biol Unit, Ctr Vasc Res, Kensington, NSW 2033, Australia.
[Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
RP Hanke, T (reprint author), Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England.
EM tomas.hanke@imm.ox.ac.uk
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Liljestrom, Peter/0000-0002-2132-0981;
Ljungberg, Karl/0000-0001-7192-6204
FU Medical Research Council (MRC UK); Dutch Cancer Society [RUL 2000-2200];
Australian Research Council (ARC) [DP0452362]; National Institute of
Allergy and Infectious Diseases, NIH (USA); Swedish Research Council
FX This work was supported by the Medical Research Council (MRC UK), the
Dutch Cancer Society grant RUL 2000-2200, the Australian Research
Council (ARC; DP0452362), the National Institute of Allergy and
Infectious Diseases, NIH (USA), and the Swedish Research Council. DAP is
an MRC UK Senior Clinical Fellow; T.H. is a Jenner Institute
Investigator; V.V. is an ARC Future Fellow; M.F.Q. is a Marie Curie
International Outgoing Research Fellow. The authors would like to thank
David Watkins for tissue typing the animals and the International AIDS
Vaccine Initiative (IAVI) for providing the HIVconsv-derived peptides.
NR 56
TC 45
Z9 46
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUL
PY 2010
VL 40
IS 7
BP 1973
EP 1984
DI 10.1002/eji.201040344
PG 12
WC Immunology
SC Immunology
GA 629SS
UT WOS:000280220600027
PM 20468055
ER
PT J
AU Vamecq, J
Maurois, P
Pages, N
Bac, P
Stables, JP
Gressens, P
Stanicki, D
Eynde, JJV
AF Vamecq, Joseph
Maurois, Pierre
Pages, Nicole
Bac, Pierre
Stables, James P.
Gressens, Pierre
Stanicki, Dimitri
Eynde, Jean Jacques Vanden
TI 1,2-Ethane bis-1-amino-4-benzamidine is active against several brain
insult and seizure challenges through anti-NMDA mechanisms targeting the
H-3-TCP binding site and antioxidant action
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Bis-benzamidines; 1,2-Ethane bis-1-amino-4-benzamidine; (EBAB);
Ibotenate challenge; seizure tests; (TCP)-T-3-binding site; Magnesium
deficiency-dependent; audiogenic seizures (MDDAS)
ID IN-VITRO; LINKED BISBENZAMIDINES; CELL-DEATH; RAT-BRAIN; RECEPTOR; MICE;
MODEL; NEUROPROTECTION; ANTICONVULSANT; MK-801
AB Five bis-benzamidines were screened towards murine magnesium deficiency-dependent audiogenic seizures, unravelling two compounds with efficacious doses 50 (ED50) less than 10 mg/kg. They were also screened against maximal electroshock and subcutaneous pentylenetetrazole-induced seizures, and explored for superoxide -scavenging activity. 1,2-Ethane bis-1-amino-4-benzamidine (EBAB) was selected and evaluated in 6 Hz seizure test (ED50 = 49 mg/kg) and at 4 mu g/kg in focal cerebral ibotenate poisoning in pups (sizes of both white and grey matter wounds were halved). EBAB was further tested on NMDA-induced seizures in mice (ED50 = 6 mg/kg) and on H-3-TC-binding to a rodent cerebral preparation (IC50 = 1.4 mu M). Taken as a whole, present data emphasise the suitability of bis-benzamidines as templates for designing brain protective compounds. (c) 2010 Elsevier Masson SAS. All rights reserved.
C1 [Vamecq, Joseph] Univ Lille 2, Res Branch, Fac Med, Inserm Univ 045131, F-59800 Lille, France.
[Vamecq, Joseph] Ctr Hosp Reg & Univ Lille, Ctr Biol & Pathol Pierre Marie Degand, Dept Biochim & Biol Mol, Lab Endocrinol Metab Nutr & Oncol, F-59037 Lille, France.
[Maurois, Pierre; Pages, Nicole; Bac, Pierre] Univ Paris 11, Fac Pharm, F-92290 Chatenay Malabry, France.
[Maurois, Pierre; Pages, Nicole; Bac, Pierre] CNRS, UMR 8162, IFR 13, Ctr Chirurg Marie Lannelongue, Le Plessis Robinson, France.
[Pages, Nicole] Univ Strasbourg 1, Fac Pharm, Toxicol Lab, Illkirch Graffenstaden, France.
[Stables, James P.] NINDS, Preclin Pharmacol Sect, Epilepsy Branch, DCDND,NIH,Neurosci Ctr, Rockville, MD 20892 USA.
[Gressens, Pierre] Hop Robert Debre, INSERM, U676, F-75019 Paris, France.
[Gressens, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR02, Paris, France.
[Gressens, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR25, Paris, France.
[Stanicki, Dimitri; Eynde, Jean Jacques Vanden] Univ Mons, Organ Chem Lab, B-7000 Mons, Belgium.
RP Vamecq, J (reprint author), Univ Lille 2, Res Branch, Fac Med, Inserm Univ 045131, F-59800 Lille, France.
EM joseph.vamecq@inserm.fr
OI Gressens, Pierre/0000-0002-0909-4221
FU Belgian F.R.I.A. (Fonds pour la formation de la Recherche dans
l'Industrie et l'Agriculture)
FX DS was sponsored by the Belgian F.R.I.A. (Fonds pour la formation de la
Recherche dans l'Industrie et l'Agriculture).
NR 37
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUL
PY 2010
VL 45
IS 7
BP 3101
EP 3110
DI 10.1016/j.ejmech.2010.03.044
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 609AF
UT WOS:000278626400049
PM 20427101
ER
PT J
AU Nayak, TK
Regino, CAS
Wong, KJ
Milenic, DE
Garmestani, K
Baidoo, KE
Szajek, LP
Brechbiel, MW
AF Nayak, Tapan K.
Regino, Celeste A. S.
Wong, Karen J.
Milenic, Diane E.
Garmestani, Kayhan
Baidoo, Kwamena E.
Szajek, Lawrence P.
Brechbiel, Martin W.
TI PET imaging of HER1-expressing xenografts in mice with
Y-86-CHX-AaEuro(3)-DTPA-cetuximab
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE PET imaging; HER1; Cetuximab; Radioimmunoimaging; Y-86
ID METASTATIC COLORECTAL-CANCER; COPPER-64-LABELED MONOCLONAL-ANTIBODY;
CETUXIMAB PLUS IRINOTECAN; EGFR EXPRESSION; RECEPTOR-BINDING; TYROSINE
KINASE; KRAS MUTATIONS; BIODISTRIBUTION; CARCINOMA; DOSIMETRY
AB Cetuximab is a recombinant, human/mouse chimeric IgG(1) monoclonal antibody that binds to the epidermal growth factor receptor (EGFR/HER1). Cetuximab is approved for the treatment of patients with HER1-expressing metastatic colorectal cancer. Limitations in currently reported radiolabeled cetuximab for PET applications prompted the development of Y-86-CHX-AaEuro(3)-DTPA-cetuximab as an alternative for imaging HER1-expressing cancer. Y-86-CHX-AaEuro(3)-DTPA-cetuximab can also serve as a surrogate marker for Y-90 therapy.
Bifunctional chelate, CHX-AaEuro(3)-DTPA was conjugated to cetuximab and radiolabeled with Y-86. In vitro immunoreactivity was assessed in HER1-expressing A431 cells. In vivo biodistribution, PET imaging and noncompartmental pharmacokinetics were performed in mice bearing HER1-expressing human colorectal (LS-174T and HT29), prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor xenografts. Receptor blockage was demonstrated by coinjection of either 0.1 or 0.2 mg cetuximab.
Y-86-CHX-AaEuro(3)-DTPA-cetuximab was routinely prepared with a specific activity of 1.5-2 GBq/mg and in vitro cell-binding in the range 65-75%. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the radiotracer and clearance from nonspecific organs. In LS-174T tumor-bearing mice injected with Y-86-CHX-AaEuro(3)-DTPA-cetuximab alone, Y-86-CHX-AaEuro(3)-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake values at 3 days were 29.3 +/- 4.2, 10.4 +/- 0.5 and 6.4 +/- 0.3%ID/g, respectively, demonstrating dose-dependent blockage of the target. Tumors were clearly visualized 1 day after injecting 3.8-4.0 MBq Y-86-CHX-AaEuro(3)-DTPA-cetuximab. Quantitative PET revealed the highest tumor uptake in LS-174T (29.55 +/- 2.67%ID/cm(3)) and the lowest tumor uptake in PC-3 (15.92 +/- 1.55%ID/cm(3)) xenografts at 3 days after injection. Tumor uptake values quantified by PET were closely correlated (r (2) = 0.9, n = 18) with values determined by biodistribution studies.
This study demonstrated the feasibility of preparation of high specific activity Y-86-CHX-AaEuro(3)-DTPA-cetuximab and its application for quantitative noninvasive PET imaging of HER1-expressing tumors. Y-86-CHX-AaEuro(3)-DTPA-cetuximab offers an attractive alternative to previously labeled cetuximab for PET and further investigation for clinical translation is warranted.
C1 [Nayak, Tapan K.; Regino, Celeste A. S.; Milenic, Diane E.; Garmestani, Kayhan; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Wong, Karen J.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Szajek, Lawrence P.] NIH, PET Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), 10 Ctr Dr,MSC 1002,Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM tapann@gmail.com; martinwb@mail.nih.gov
OI Nayak, Tapan/0000-0002-3706-6092
FU National Institutes of Health, National Cancer Institute; Center for
Cancer Research; United States Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the United States Department of Health and Human
Services. We are also grateful to Jurgen Seidel and Michael Green
(National Cancer Institute, National Institutes of Health, Bethesda, MD)
for technical input on the operations of NIH ATLAS small-animal PET
scanner.
NR 38
TC 37
Z9 37
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUL
PY 2010
VL 37
IS 7
BP 1368
EP 1376
DI 10.1007/s00259-009-1370-z
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 611PV
UT WOS:000278833100014
PM 20155263
ER
PT J
AU Schlett, CL
Kwait, DC
Mahabadi, AA
Bamberg, F
O'Donnell, CJ
Fox, CS
Hoffmann, U
AF Schlett, Christopher L.
Kwait, Dylan C.
Mahabadi, Amir A.
Bamberg, Fabian
O'Donnell, Christopher J.
Fox, Caroline S.
Hoffmann, Udo
TI Simple area-based measurement for multidetector computed tomography to
predict left ventricular size
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Multidetector computed tomography; Left ventricle; Left ventricular
size; Cardio-thoracic ratio; Direct transverse cardiac diameter;
Framingham Heart Study
ID ACUTE PULMONARY-EMBOLISM; CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION;
CARDIOTHORACIC RATIO; CHEST-PAIN; MORTALITY; MASS; CT; FRAMINGHAM;
SURVIVAL
AB Measures of left ventricular (LV) mass and dimensions are independent predictors of morbidity and mortality. We determined whether an axial area-based method by computed tomography (CT) provides an accurate estimate of LV mass and volume.
A total of 45 subjects (49% female, 56.0 +/- 12 years) with a wide range of LV geometry underwent contrast-enhanced 64-slice CT. LV mass and volume were derived from 3D data. 2D images were analysed to determine LV area, the direct transverse cardiac diameter (dTCD) and the cardiothoracic ratio (CTR). Furthermore, feasibility was confirmed in 100 Framingham Offspring Cohort subjects.
2D measures of LV area, dTCD and CTR were 47.3 +/- 8 cm(2), 14.7 +/- 1.5 cm and 0.54 +/- 0.05, respectively. 3D-derived LV volume (end-diastolic) and mass were 148.9 +/- 45 cm(3) and 124.2 +/- 34 g, respectively. Excellent inter- and intra-observer agreement were shown for 2D LV area measurements (both intraclass correlation coefficients (ICC) = 0.99, p < 0.0001) and could be confirmed on non-contrast CT. The measured 2D LV area was highly correlated to LV volume, mass and size (r = 0.68; r = 0.73; r = 0.82; all p < 0.0001, respectively). On the other hand, CTR was not correlated to LV volume, mass, size or 2D LV area (all p > 0.27).
Compared with traditionally used CTR, LV size can be accurately predicted based on a simple and highly reproducible axial LV area-based measurement.
C1 [Schlett, Christopher L.; Kwait, Dylan C.; Mahabadi, Amir A.; Bamberg, Fabian; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Schlett, Christopher L.; Kwait, Dylan C.; Mahabadi, Amir A.; Bamberg, Fabian; Fox, Caroline S.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Bamberg, Fabian] Univ Munich, Munich, Germany.
[Bamberg, Fabian] Univ Hosp Munich, Dept Clin Radiol, Munich, Germany.
[O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Blood Insts Framingham Heart St, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
FU National Heart, Lung and Blood Institute [N01-HC-25195]; National
Institute of Health (NIH) [R01 HL080053]; Siemens Medical Solutions;
German Federal Ministry of Education and Research; Foundation of German
Business, Berlin
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (N01-HC-25195), National Institute of
Health (NIH, R01 HL080053), and in part by Siemens Medical Solutions.
Christopher Schlett was supported by grants from the German Federal
Ministry of Education and Research, and Foundation of German Business,
Berlin.
NR 29
TC 14
Z9 14
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD JUL
PY 2010
VL 20
IS 7
BP 1590
EP 1596
DI 10.1007/s00330-010-1720-z
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 607RA
UT WOS:000278522800006
PM 20204649
ER
PT J
AU Tsivian, M
Moreira, DM
Caso, JR
Mouraviev, V
Madden, JF
Bratslavsky, G
Robertson, CN
Albala, DM
Polascik, TJ
AF Tsivian, Matvey
Moreira, Daniel M.
Caso, Jorge R.
Mouraviev, Vladimir
Madden, John F.
Bratslavsky, Gennady
Robertson, Cary N.
Albala, David M.
Polascik, Thomas J.
TI Predicting Occult Multifocality of Renal Cell Carcinoma
SO EUROPEAN UROLOGY
LA English
DT Article
DE Renal cell carcinoma; Nephron-sparing surgery; Partial nephrectomy;
Multifocal; Occult; Multicentricity
ID PARTIAL NEPHRECTOMY; HISTOLOGICAL PATTERN; FAMILY-HISTORY; TUMORS;
SURVIVAL; OUTCOMES; CANCER; FEASIBILITY; CANDIDATES; ACCURACY
AB Background: Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.
Objective: Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC.
Design, setting, and participants: We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties.
Interventions: All patients underwent radical nephrectomy.
Measurements: Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms.
Results and limitations: The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively.
Conclusions: Our data suggest that occult multifocal RCC is more frequently associated with small (2-4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Tsivian, Matvey; Moreira, Daniel M.; Caso, Jorge R.; Mouraviev, Vladimir; Robertson, Cary N.; Albala, David M.; Polascik, Thomas J.] Duke Univ, Med Ctr, Dept Surg, Div Urol, Durham, NC 27710 USA.
[Madden, John F.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Polascik, TJ (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Urol, DUMC 2804, Durham, NC 27710 USA.
EM polas001@mc.duke.edu
NR 31
TC 13
Z9 14
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD JUL
PY 2010
VL 58
IS 1
BP 118
EP 126
DI 10.1016/j.eururo.2010.03.011
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 606HR
UT WOS:000278414100018
PM 20346577
ER
PT J
AU Owen, N
Healy, GN
Matthews, CE
Dunstan, DW
AF Owen, Neville
Healy, Genevieve N.
Matthews, Charles E.
Dunstan, David W.
TI Too Much Sitting: The Population Health Science of Sedentary Behavior
SO EXERCISE AND SPORT SCIENCES REVIEWS
LA English
DT Review
DE environmental and social change; TV time; breaks in sedentary time;
accelerometer measurement; blood glucose; triglycerides; metabolic
health
ID TELEVISION VIEWING TIME; INTENSITY PHYSICAL-ACTIVITY; METABOLIC RISK;
CARDIOVASCULAR-DISEASE; ENERGY-EXPENDITURE; LIFE-STYLE; AUSTRALIAN
ADULTS; PLASMA-GLUCOSE; UNITED-STATES; OBESITY
AB OWEN, N., G.N. HEALY, C.E. MATTHEWS, and D.W. DUNSTAN. Too much sitting: the population health science sedentary behavior. Exerc. Sport Sci. Rev., Vol. 38, No. 3, pp. 105-113, 2010. Even when adults meet physical activity guidelines, sitting for prolonged periods can compromise metabolic health. Television (TV) time and objective measurement studies show associations, and breaking up sedentary time is beneficial. Sitting time, TV time, and time sitting in automobiles increase premature mortality risk. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required.
C1 [Owen, Neville; Healy, Genevieve N.] Univ Queensland, Canc Prevent Res Ctr, Sch Populat Hlth, Brisbane, Qld, Australia.
[Owen, Neville; Healy, Genevieve N.; Dunstan, David W.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Owen, N (reprint author), Univ Queensland, Canc Prevent Res Ctr, Sch Populat Hlth, Level 3,Publ Hlth Bldg,Herston Rd, Herston, Qld 4006, Australia.
EM n.owen@sph.uq.edu.au
RI Healy, Genevieve/A-7408-2008; Dunstan, David/E-8473-2010; Owen,
Neville/F-8329-2010; Owen, Neville/K-5986-2012; matthews,
Charles/E-8073-2015;
OI Healy, Genevieve/0000-0001-7093-7892; Dunstan,
David/0000-0003-2629-9568; matthews, Charles/0000-0001-8037-3103; Owen,
Neville/0000-0003-2784-4820
FU Queensland Health; National Health and Medical Research Council (NHMRC)
[301200, 569940, 569861]; National Heart Foundation of Australia [PH 08B
3905]; Victorian Health Promotion Foundation
FX N. Owen is supported by a Queensland Health Core Research Infrastructure
grant and by a National Health and Medical Research Council (NHMRC)
Program grant funding (no. 301200; no. 569940). G.N. Healy is supported
by an NHMRC (no. 569861)/National Heart Foundation of Australia (PH 08B
3905) Postdoctoral Fellowship. D.W. Dunstan is supported by a Victorian
Health Promotion Foundation Public Health Research Fellowship.
NR 52
TC 614
Z9 629
U1 35
U2 218
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0091-6331
J9 EXERC SPORT SCI REV
JI Exerc. Sport Sci. Rev.
PD JUL
PY 2010
VL 38
IS 3
BP 105
EP 113
DI 10.1097/JES.0b013e3181e373a2
PG 9
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 623RJ
UT WOS:000279759200003
PM 20577058
ER
PT J
AU Zhang, K
Johnson, B
Pennell, D
Ray, W
Sebastianelli, W
Slobounov, S
AF Zhang, K.
Johnson, B.
Pennell, D.
Ray, W.
Sebastianelli, W.
Slobounov, S.
TI Are functional deficits in concussed individuals consistent with white
matter structural alterations: combined FMRI & DTI study
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE Mild traumatic brain injury (MTBI); Functional magnetic resonance
imaging (FMRI); Diffusion tensor imaging (DTI); Fractional Anisotropy
(FA); White matter (WM)
ID TRAUMATIC BRAIN-INJURY; DIFFUSE AXONAL INJURY; HEAD-INJURY; TENSOR;
MILD; ABNORMALITIES; IMAGES; MRI
AB There is still controversy in the literature whether a single episode of mild traumatic brain injury (MTBI) results in short-term functional and/or structural deficits as well as any induced long-term residual effects. With the inability of traditional structural brain imaging techniques to accurately diagnosis MTBI, there is hope that more advanced applications like functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) will be more specific in diagnosing MTBI. In this study, 15 subjects who have recently suffered from sport-related MTBI and 15 age-matched normal controls underwent both fMRI and DTI to investigate the possibility of traumatic axonal injury associated with functional deficits in recently concussed but asymptomatic individuals. There are several findings of interest. First, MTBI subjects had a more disperse brain activation pattern with additional increases in activity outside of the shared regions of interest (ROIs) as revealed by FMRI blood oxygen level-dependent (BOLD) signals. The MTBI group had additional activation in the left dorsal-lateral prefrontal cortex during encoding phase of spatial navigation working memory task that was not observed in normal controls. Second, neither whole-brain analysis nor ROI analysis showed significant alteration of white matter (WM) integrity in MTBI subjects as evidenced by fractional anisotropy FA (DTI) data. It should be noted, however, there was a larger variability of fractional anisotropy (FA) in the genu, and body of the corpus callosum in MTB subjects. Moreover, we observed decreased diffusivity as evidenced by apparent diffusion coefficient (ADC) at both left and right dorsolateral prefrontal cortex (DL-PFC) in MTBI subjects (P < 0.001). There was also a positive correlation (P < 0.05) between ADC and % change of fMRI BOLD signals at DL-PFC in MTBI subjects, but not in normal controls. Despite these differences we conclude that overall, no consistent findings across advanced brain imaging techniques (fMRI and DTI) were observed. Whether the lack of consistency across research techniques (fMRI & DTI) is due to time frame of scanning, unique nature of MTBI and/or technological issues involved in FA and Apparent Diffusion Coefficient (ADC) quantification is yet to be determined.
C1 [Slobounov, S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Zhang, K.; Johnson, B.; Slobounov, S.] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
[Ray, W.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
[Pennell, D.] Penn State Univ, Chandlee Lab, Social Life & Engn Sci Imaging Ctr, University Pk, PA 16802 USA.
[Sebastianelli, W.; Slobounov, S.] Penn State Univ, Ctr Sport Med, University Pk, PA 16802 USA.
[Sebastianelli, W.; Slobounov, S.] Penn State Univ, Hershey Med Sch, University Pk, PA 16802 USA.
RP Slobounov, S (reprint author), NINDS, NIH, MSC10 Ctr Dr, Bethesda, MD 20892 USA.
EM sms18@psu.edu
FU NIH [RO1 NS056227-01A2]
FX This study was supported by NIH Grant RO1 NS056227-01A2 "Identification
of Athletes at Risk for Traumatic Brain Injury'' awarded to Dr.
Slobounov, PI.
NR 45
TC 83
Z9 84
U1 2
U2 22
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD JUL
PY 2010
VL 204
IS 1
BP 57
EP 70
DI 10.1007/s00221-010-2294-3
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 610MO
UT WOS:000278737200006
PM 20496060
ER
PT J
AU Mizelle, JC
Forrester, L
Hallett, M
Wheaton, LA
AF Mizelle, J. C.
Forrester, Larry
Hallett, Mark
Wheaton, Lewis A.
TI Theta frequency band activity and attentional mechanisms in visual and
proprioceptive demand
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE EEG; Theta band; Sensorimotor control
ID ANTERIOR CINGULATE CORTEX; PRIMATE PREFRONTAL CORTEX; EVENT-RELATED
FMRI; WORKING-MEMORY; POSTERIOR CINGULATE; SPATIAL ATTENTION; MOTOR
AREAS; BRAIN; INTEGRATION; ACTIVATION
AB In a companion manuscript we reported reduced electroencephalographic (EEG) activation at traditional sensorimotor areas in knee movements with high levels of task difficulty modulated by varying visual and proprioceptive sensory demands. Given that reduced cortical activity with more complex tasks is counter-intuitive, we suggested that high order cognitive-motor areas may show increased EEG activation to compensate for the observed decrease in sensorimotor regions. To test this hypothesis, we evaluated theta band activation at anterior frontal regions in a secondary analysis of our previous data. Unlike activation at sensorimotor areas, anterior frontal responses increased with each level of task difficulty as modulated by precision of visual targeting and/or proprioceptive demands from adding masses to the leg. Activity was increased as both unimodal visual and proprioceptive requirements became more demanding, but showed greater sensitivity to visual over proprioceptive processing requirements. Each level of bimodal task demands showed increasing activation, which was consistently greater when modulated through visual demands. These results are consistent with our hypothesis of increased contribution of anterior frontal regions for motor control in lower extremity movements with increasing sensory demands and further support different mechanisms for internally and externally guided movement.
C1 [Mizelle, J. C.; Wheaton, Lewis A.] Georgia Inst Technol, Sch Appl Physiol, Atlanta, GA 30332 USA.
[Mizelle, J. C.; Forrester, Larry] Baltimore Dept Vet Affairs, Baltimore, MD USA.
[Mizelle, J. C.; Forrester, Larry; Wheaton, Lewis A.] Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA.
[Forrester, Larry] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Wheaton, LA (reprint author), Georgia Inst Technol, Sch Appl Physiol, 281 Ferst Dr,Room 104, Atlanta, GA 30332 USA.
EM lewis.wheaton@ap.gatech.edu
RI Wheaton, Lewis /B-4482-2009
OI Wheaton, Lewis /0000-0003-0771-0294
FU Veterans Affairs 2008 Pre-Doctoral Associated Health Rehabilitation
Research Fellowship Program; National Institutes of Health National
Center for Medical Rehabilitation Research [T32-HD041899-01A1]; Veterans
Affairs Center for Excellence in Exercise and Robotics for Neurological
Disorders [COEB3688R]; Veterans Affairs Stroke Research Enhancement;
Veterans Affairs Rehabilitation Research and Development, Advanced
Research Career Development [B3390K]; Baltimore Veterans Affairs
Geriatrics Research, Education, and Clinical Center; NINDS Intramural
Research Program
FX This study was supported by the Veterans Affairs 2008 Pre-Doctoral
Associated Health Rehabilitation Research Fellowship Program; National
Institutes of Health National Center for Medical Rehabilitation Research
T32 Award (#T32-HD041899-01A1); Veterans Affairs Center for Excellence
in Exercise and Robotics for Neurological Disorders (COE#B3688R);
Veterans Affairs Stroke Research Enhancement Award Program; Veterans
Affairs Rehabilitation Research and Development, Advanced Research
Career Development Award (B3390K); Baltimore Veterans Affairs Geriatrics
Research, Education, and Clinical Center. Dr. Hallett is supported by
the NINDS Intramural Research Program.
NR 52
TC 5
Z9 5
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD JUL
PY 2010
VL 204
IS 2
BP 189
EP 197
DI 10.1007/s00221-010-2297-0
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 616FX
UT WOS:000279195500005
PM 20532491
ER
PT J
AU Nita-Lazar, M
Rebustini, I
Walker, J
Kukuruzinska, MA
AF Nita-Lazar, Mihai
Rebustini, Ivan
Walker, Janice
Kukuruzinska, Maria A.
TI Hypoglycosylated E-cadherin promotes the assembly of tight junctions
through the recruitment of PP2A to adherens junctions
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Adherens junctions; E-cadherin N-glycosylation; PP2A; Tight junctions
ID PROTEIN PHOSPHATASE 2A; N-GLYCOSYLATION GENE; CELL-CELL-ADHESION;
ACTIN-FILAMENTS; ALPHA-CATENIN; BETA-CATENIN; COMPLEX; INVOLVEMENT;
EXPRESSION; POLARITY
AB Epithelial cell cell adhesion is controlled by multiprotein complexes that include E-cadherin-mediated adherens junctions (AJs) and ZO-1-containing tight junctions (TJs). Previously, we reported that reduction of E-cadherin N-glycosylation in normal and cancer cells promoted stabilization of AJs through changes in the composition and cytoskeletal association of E-cadherin scaffolds. Here, we show that enhanced interaction of hypoglycosylated E-cadherin-containing AJs with protein phosphatase 2A (PP2A) represents a mechanism for promoting TJ assembly. In MDCK cells, attenuation of cellular N-glycosylation with siRNA to DPAGT1, the first gene in the N-glycosylation pathway, reduced N-glycosylation of surface E-cadherin and resulted in increased recruitment of stabilizing proteins gamma-catenin, alpha-catenin, vinculin and PP2A to AJs. Greater association of PP2A with AJs correlated with diminished binding of PP2A to ZO-1 and claudin- 1 and with increased pools of serine-phosphorylated ZO-1 and claudin-1. More ZO-1 was found in complexes with occludin and claudin-1, and this corresponded to enhanced transepithelial resistance (TER), indicating physiological assembly of TJs. Similar maturation of AJs and TJs was detected after transfection of MDCK cells with the hypoglycosylated E-cadherin variant, V13. Our data indicate that E-cadherin N-glycans coordinate the maturity of AJs with the assembly of TJs by affecting the association of PP2A with these junctional complexes. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Nita-Lazar, Mihai; Kukuruzinska, Maria A.] Boston Univ, Med Ctr, Dept Mol & Cell Biol, Boston, MA 02118 USA.
[Rebustini, Ivan] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA.
[Walker, Janice] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
RP Kukuruzinska, MA (reprint author), Boston Univ, Med Ctr, Dept Mol & Cell Biol, Boston, MA 02118 USA.
EM mkukuruz@bu.edu
RI Nita-Lazar, Mihai/Q-2206-2016
OI Nita-Lazar, Mihai/0000-0002-5099-1311
FU NIH [DE010183, DE015304, R24 EY 014798]
FX We thank A. Sue Menko for helpful discussions and for the use of
confocal facility. This work was supported by NIH Grants DE010183 (MAK)
and DE015304 (MAK) and R24 EY 014798 (A. Sue Menko).
NR 57
TC 23
Z9 24
U1 1
U2 7
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD JUL 1
PY 2010
VL 316
IS 11
BP 1871
EP 1884
DI 10.1016/j.yexcr.2010.02.008
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 606JZ
UT WOS:000278422600010
PM 20156436
ER
PT J
AU Cao, XG
Liu, M
Tuo, JS
Shen, DF
Chan, CC
AF Cao, Xiaoguang
Liu, Melissa
Tuo, Jingsheng
Shen, Defen
Chan, Chi-Chao
TI The effects of quercetin in cultured human RPE cells under oxidative
stress and in Ccl2/Cx3cr1 double deficient mice
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE quercetin; RPE; age-related macular degeneration; oxidative stress;
inflammation; apoptosis; AMD mouse model
ID RETINAL-PIGMENT EPITHELIUM; MITOCHONDRIAL-DNA DAMAGE; MACULAR
DEGENERATION; HYDROGEN-PEROXIDE; IN-VITRO; LUNG INFLAMMATION; ACID
HYDROPEROXIDE; LIPID-PEROXIDATION; GENE-EXPRESSION; OUTER SEGMENTS
AB Quercetin, a member of the flavonoid family, is one of the most prominent dietary antioxidants. This study investigates the mechanisms for the effects of quercetin on cultured human RPE cells and in Ccl2/Cx3cr1 double knock-out (DKO) mice, which spontaneously develop progressive retinal lesions mimicking age-related macular degeneration (AMD). In the in vitro experiment, cultured ARPE-19 cells were exposed to 1 mM H(2)O(2) with or without 50 mu M quercetin for 2 h. Cellular viability, mitochondrial function, and apoptosis were assessed using crystal violet staining, MTT assay, and comet assay, respectively. Apoptotic molecular transcripts of BCL-2, BAX, MUD, CASPASE-3 and CASPASE-9 were measured by RQ-PCR. COX activity and nitric oxide (NO) level were determined in the supernatant of the culture medium. Quercetin treatment protected ARPE-19 cells from H(2)O(2)-induced oxidative injury, enhanced BCL-2 transcript levels, increased the BCL-2/BAX ratio, suppressed the transcription of proapoptotic factors such as BAX, FADD, CASPASE-3 and CASPASE-9, inhibited the transcription of inflammatory factors such as TNF-alpha, COX-2 and INOS, and decreased the levels of COX and NO in the culture medium. In the in vivo experiment, DKO and C57/B6 mice were treated with 25 mg/kg/day quercetin by intraperitoneal injection daily for two months. Funduscopy was performed monthly. After two months, serum was collected to measure NADP(+)/NADPH, COX, PGE-2, and NO levels. The eyes were harvested for histology and A2E measurement. Ocular transcripts of Bcl-2, Bax, Cox-2, Inos, Tnf-alpha, Fas, Fast and Caspase-3 were detected by RQ-PCR. Quercetin treatment did not reverse the progression of retinal lesions in DKO mice funduscopically or histologically. Although quercetin treatment could recover systemic anti-oxidative capacity, suppress the systemic expression of NO, COX and PGE-2, and decrease ocular A2E levels, it could not effectively suppress the transcripts of the ocular inflammatory factors Trif-a, Cox-2 and Inos, or the pro-apoptotic factors Fas, FasL and Caspase-3 in DKO mice. Our data demonstrate that quercetin can protect human RPE cells from oxidative stress in vitro via inhibition of pro-inflammatory molecules and direct inhibition of the intrinsic apoptosis pathway. However, quercetin (25 mg/kg/day) does not improve the retinal AMD-like lesions in the Ccl2(-/-)/Cx3cr1(-/-) mice, likely due to its insufficient suppression of the inflammatory and apoptosis pathways in the eye. Published by Elsevier Ltd.
C1 [Cao, Xiaoguang; Liu, Melissa; Tuo, Jingsheng; Shen, Defen; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Cao, Xiaoguang] Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU National Eye Institute, NIH
FX The study was supported by the Intramural Research Program of the
National Eye Institute, NIH.
NR 89
TC 26
Z9 28
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUL
PY 2010
VL 91
IS 1
BP 15
EP 25
DI 10.1016/j.exer.2010.03.016
PG 11
WC Ophthalmology
SC Ophthalmology
GA 611HP
UT WOS:000278804700003
PM 20361964
ER
EF