FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Spitz, MR
Amos, CI
Bierut, LJ
Caporaso, NE
AF Spitz, Margaret R.
Amos, Christopher I.
Bierut, Laura J.
Caporaso, Neil E.
TI Cotinine Conundrum-A Step Forward but Questions Remain
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID RECEPTOR SUBUNIT GENES; LUNG-CANCER; NICOTINE DEPENDENCE; SUSCEPTIBILITY
LOCUS; RISK; ASSOCIATION; SMOKERS; CARCINOGEN; VARIANTS; SMOKING
C1 [Spitz, Margaret R.] Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Spitz, MR (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, 1 Baylor Plaza,MS BCM305,Ste 450A8,Cullen Bldg, Houston, TX 77030 USA.
EM spitz@bcm.edu
FU NCI NIH HHS [U19 CA148127, R01CA121197, P50 CA70907, P50 CA070907,
P01CA089392, R01CA127219]; NHGRI NIH HHS [U01 HG004422]
NR 19
TC 6
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 10
BP 720
EP 722
DI 10.1093/jnci/djs211
PG 3
WC Oncology
SC Oncology
GA 944KH
UT WOS:000304199600001
PM 22534783
ER
PT J
AU Prorok, PC
Miller, AB
Kramer, BS
AF Prorok, Philip C.
Miller, Anthony B.
Kramer, Barnett S.
TI Re: Prostate Cancer Screening in the Randomized Prostate, Lung,
Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after
13 Years of Follow-up Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
[Kramer, Barnett S.] NCI, Off Director, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Prorok, PC (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Ste 3132, Bethesda, MD 20892 USA.
EM prorokp@mail.nih.gov
NR 2
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 10
BP 793
EP 794
DI 10.1093/jnci/djs206
PG 2
WC Oncology
SC Oncology
GA 944KH
UT WOS:000304199600014
ER
PT J
AU Rao, E
Jiang, C
Ji, M
Huang, X
Iqbal, J
Lenz, G
Wright, G
Staudt, LM
Zhao, Y
McKeithan, TW
Chan, WC
Fu, K
AF Rao, E.
Jiang, C.
Ji, M.
Huang, X.
Iqbal, J.
Lenz, G.
Wright, G.
Staudt, L. M.
Zhao, Y.
McKeithan, T. W.
Chan, W. C.
Fu, K.
TI The miRNA-17 similar to 92 cluster mediates chemoresistance and enhances
tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation
SO LEUKEMIA
LA English
DT Article
DE miR-17 similar to 92 cluster; mantle cell lymphoma; PHLPP2; PTEN;
PI3K/AKT pathway
ID MICRORNA CLUSTER; MALIGNANT-LYMPHOMA; EXPRESSION; GENE; PROLIFERATION;
MIR-17-92; BIM; PROMOTES; IDENTIFICATION; AMPLIFICATION
AB The median survival of patients with mantle cell lymphoma (MCL) ranges from 3 to 5 years with current chemotherapeutic regimens. A common secondary genomic alteration detected in MCL is chromosome 13q31-q32 gain/amplification, which targets a microRNA (miRNA) cluster, miR-17 similar to 92. On the basis of gene expression profiling, we found that high level expression of C13orf25, the primary transcript from which these miRNAs are processed, was associated with poorer survival in patients with MCL (P = 0.021). We demonstrated that the protein phosphatase PHLPP2, an important negative regulator of the PI3K/AKT pathway, was a direct target of miR-17 similar to 92 miRNAs, in addition to PTEN and BIM. These proteins were down-modulated in MCL cells with overexpression of the miR-17 similar to 92 cluster. Overexpression of miR-17 similar to 92 activated the PI3K/AKT pathway and inhibited chemotherapy-induced apoptosis in MCL cell lines. Conversely, inhibition of miR-17 similar to 92 expression suppressed the PI3K/AKT pathway and inhibited tumor growth in a xenograft MCL mouse model. Targeting the miR-17 similar to 92 cluster may therefore provide a novel therapeutic approach for patients with MCL.
C1 [Rao, E.; Jiang, C.; Ji, M.; Huang, X.; Iqbal, J.; McKeithan, T. W.; Chan, W. C.; Fu, K.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Rao, E.; Jiang, C.; Ji, M.; Huang, X.; Iqbal, J.; McKeithan, T. W.; Chan, W. C.; Fu, K.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA.
[Rao, E.; Zhao, Y.] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Transplantat Biol Res Div, Beijing, Peoples R China.
[Rao, E.] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China.
[Lenz, G.] Charite, Dept Hematol Oncol & Tumor Immunol, D-13353 Berlin, Germany.
[Lenz, G.; Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wright, G.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Fu, K (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
EM kfu@unmc.edu
RI Lenz, Georg/I-6844-2012; Huang, Xin/P-8103-2014;
OI Huang, Xin/0000-0001-6778-8849; McKeithan, Timothy/0000-0003-2242-3074
FU National Institutes of Health [U01 CA114778]; Lymphoma Research
Foundation/Millennium Pharmaceuticals, Inc.; UNMC Eppley Cancer Center;
China Scholarship Council
FX This work was supported in part by the National Institutes of Health
grant U01 CA114778 to WCC; the Lymphoma Research Foundation/Millennium
Pharmaceuticals, Inc. Clinical Investigator Career Development Award to
KF; and UNMC Eppley Cancer Center Pilot Grant to KF; MJ and XH are
supported by a scholarship from the China Scholarship Council.
NR 51
TC 80
Z9 85
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2012
VL 26
IS 5
BP 1064
EP 1072
DI 10.1038/leu.2011.305
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 940IP
UT WOS:000303883500026
PM 22116552
ER
PT J
AU Moore, CR
Liu, Y
Shao, C
Covey, LR
Morse, HC
Xie, P
AF Moore, C. R.
Liu, Y.
Shao, C.
Covey, L. R.
Morse, H. C., III
Xie, P.
TI Specific deletion of TRAF3 in B lymphocytes leads to B-lymphoma
development in mice
SO LEUKEMIA
LA English
DT Letter
ID MULTIPLE-MYELOMA; CELL HOMEOSTASIS; PATHWAYS; ABNORMALITIES; MUTATIONS;
SURVIVAL; RECEPTOR; KINASE; NIK
C1 [Moore, C. R.; Liu, Y.; Covey, L. R.; Xie, P.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
[Shao, C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[Morse, H. C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
RP Moore, CR (reprint author), Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
EM xiep@rci.rutgers.edu
OI Morse, Herbert/0000-0002-9331-3705; Shao, Changshun/0000-0003-2618-9342
FU Intramural NIH HHS [ZIA AI000858-12]; NCI NIH HHS [R01 CA158402, P30
CA072720, P30CA072720]
NR 15
TC 16
Z9 18
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2012
VL 26
IS 5
BP 1122
EP 1127
DI 10.1038/leu.2011.309
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 940IP
UT WOS:000303883500037
PM 22033491
ER
PT J
AU Burd, CJ
Ward, JM
Crusselle-Davis, VJ
Kissling, GE
Phadke, D
Shah, RR
Archer, TK
AF Burd, Craig J.
Ward, James M.
Crusselle-Davis, Valerie J.
Kissling, Grace E.
Phadke, Dhiral
Shah, Ruchir R.
Archer, Trevor K.
TI Analysis of Chromatin Dynamics during Glucocorticoid Receptor Activation
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTORS; IN-VIVO; REGULATORY ELEMENTS; NUCLEAR RECEPTORS;
BREAST-CANCER; MMTV PROMOTER; GENE; COACTIVATORS; COMPLEX; BINDING
AB Steroid hormone receptors initiate a genetic program tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structure through formaldehyde-assisted isolation of regulatory elements (FAIRE). We looked at dynamic changes in FAIRE signals during GR activation specifically at regions of receptor interaction. We found a distribution of GR-responsive regions with diverse responses to activation and chromatin modulation. The majority of GR binding regions demonstrate increases in FAIRE signal in response to ligand. However, the majority GR-responsive regions shared a similar FAIRE signal in the basal chromatin state, suggesting a common chromatin structure for GR recruitment. Supporting this notion, global FAIRE sequencing (seq) data indicated an enrichment of signal surrounding the GR binding site prior to activation. Brg-1 knockdown showed response element-specific effects of ATPase-dependent chromatin remodeling. FAIRE induction was universally decreased by Brg-1 depletion, but to varying degrees in a target specific manner. Taken together, these data suggest classes of nuclear receptor response regions that react to activation through different chromatin regulatory events and identify a chromatin structure that classifies the majority of response elements tested.
C1 [Burd, Craig J.; Crusselle-Davis, Valerie J.; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Chromatin & Gene Express Grp, Mol Carcinogenesis Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Kissling, Grace E.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA.
[Phadke, Dhiral; Shah, Ruchir R.] SRA Int, Durham, NC USA.
RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Chromatin & Gene Express Grp, Mol Carcinogenesis Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
EM archer1@niehs.nih.gov
OI Burd, Craig/0000-0002-6899-6751
FU NIH, National Institute of Environmental Health Sciences [Z01
ES071006-11]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (Z01
ES071006-11).
NR 46
TC 20
Z9 20
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2012
VL 32
IS 10
BP 1805
EP 1817
DI 10.1128/MCB.06206-11
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 939TP
UT WOS:000303840100004
PM 22451486
ER
PT J
AU Postnikov, YV
Kurahashi, T
Zhou, M
Bustin, M
AF Postnikov, Yuri V.
Kurahashi, Toshihiro
Zhou, Ming
Bustin, Michael
TI The Nucleosome Binding Protein HMGN1 Interacts with PCNA and Facilitates
Its Binding to Chromatin
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NUCLEAR ANTIGEN PCNA; CHROMOSOMAL-PROTEINS; DNA-DAMAGE; HISTONE H1;
MISMATCH REPAIR; LIVING CELLS; IN-VIVO; REPLICATION; ACTIVATION;
MOBILITY
AB Proliferating cell nuclear antigen (PCNA) is a ubiquitous protein that interacts with multiple partners and regulates nuclear activities, including chromatin assembly, histone modifications, replication, and DNA damage repair. The role of specific partners in regulating PCNA activities is not fully understood. Here we identify the nucleosome binding protein HMGN1 as a new PCNA-interacting protein that enhances the binding of PCNA to chromatin but not to purified DNA. Two tetrapeptides in the conservative domain of HMGN1 contain amino acids necessary for the binding of HMGN1 to PCNA. Deletion of both tetrapeptides abolishes the HMGN1-PCNA interaction. PCNA preferentially binds to the linker DNA adjacent to an HMGN-containing nucleosome. In living cells, loss of HMGN1 decreases the rate of PCNA recruitment to damaged DNA sites. Our study identifies a new factor that facilitates the interaction of PCNA with chromatin and provides insights into mechanisms whereby nucleosome binding architectural proteins affect the cellular phenotype.
C1 [Postnikov, Yuri V.; Kurahashi, Toshihiro; Bustin, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Zhou, Ming] NCI, Lab Prote & Analyt Technol, NIH, Frederick, MD 21701 USA.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA.
EM bustin@helix.nih.gov
RI Bustin, Michael/G-6155-2015
FU Center for Cancer Research, NCI, NIH; NCI, NIH [N01-CO-12400]; JSPS from
the Japanese Biomedical and Behavioral Research at NIH
FX This project was supported by the Center for Cancer Research, intramural
program of the NCI, NIH, by contract number N01-CO-12400 granted by NCI,
NIH, and by a JSPS research fellowship from the Japanese Biomedical and
Behavioral Research at NIH to T.K. The yeast RFC and human RFC
preparations were generous gifts from Paul Modrich (Duke University).
NR 48
TC 10
Z9 10
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2012
VL 32
IS 10
BP 1844
EP 1854
DI 10.1128/MCB.06429-11
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 939TP
UT WOS:000303840100007
PM 22393258
ER
PT J
AU Bhatt, S
Xiao, Z
Meng, ZJ
Katzenellenbogen, BS
AF Bhatt, Shweta
Xiao, Zhen
Meng, Zhaojing
Katzenellenbogen, Benita S.
TI Phosphorylation by p38 Mitogen-Activated Protein Kinase Promotes
Estrogen Receptor alpha Turnover and Functional Activity via the SCFSkp2
Proteasomal Complex
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BREAST-CANCER-CELLS; HUMAN PROGESTERONE-RECEPTORS; UBIQUITIN LIGASE;
TAMOXIFEN RESISTANCE; AROMATASE INHIBITORS; GENE-EXPRESSION; ER-ALPHA;
TRANSCRIPTIONAL ACTIVITY; ENDOCRINE RESISTANCE; 26S PROTEASOME
AB The nuclear hormone receptor estrogen receptor alpha (ER alpha) mediates the actions of estrogens in target cells and is a master regulator of the gene expression and proliferative programs of breast cancer cells. The presence of ER alpha in breast cancer cells is crucial for the effectiveness of endocrine therapies, and its loss is a hallmark of endocrine-insensitive breast tumors. However, the molecular mechanisms underlying the regulation of the cellular levels of ER alpha are not fully understood. Our findings reveal a unique cellular pathway involving the p38 mitogen-activated protein kinase (p38MAPK) -mediated phosphorylation of ER alpha at Ser-294 that specifies its turnover by the SCFSkp2 proteasome complex. Consistently, we observed an inverse relationship between ER alpha and Skp2 or active p38MAPK in breast cancer cell lines and human tumors. ER alpha regulation by Skp2 was cell cycle stage dependent and critical for promoting the mitogenic effects of estradiol via ER alpha. Interestingly, by the knockdown of Skp2 or the inhibition of p38MAPK, we restored functional ER alpha protein levels and the control of gene expression and proliferation by estrogen and antiestrogen in ER alpha-negative breast cancer cells. Our findings highlight a novel pathway with therapeutic potential for restoring ER alpha and the responsiveness to endocrine therapy in some endocrine-insensitive ER alpha-negative breast cancers.
C1 [Katzenellenbogen, Benita S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
[Bhatt, Shweta] Univ Illinois, Dept Biochem, Urbana, IL USA.
[Xiao, Zhen; Meng, Zhaojing] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Katzenellenbogen, BS (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
EM katzenel@uiuc.edu
FU NIH (National Center for Complementary and Alternative Medicines
[NCCAM]) [1 P50 AT006268]; NIH (Office of Dietary Supplements [ODS]);
NIH (National Cancer Institute [NCI]) [HHSN261200800001E]; Breast Cancer
Research Foundation
FX This work was supported by a grant from the NIH (1 P50 AT006268 [B.S.K.]
from the National Center for Complementary and Alternative Medicines
[NCCAM], the Office of Dietary Supplements [ODS], and the National
Cancer Institute [NCI]). This work was also supported by a grant from
The Breast Cancer Research Foundation (B.S.K.) and in part with federal
funds from the National Cancer Institute, NIH, under contract
HHSN261200800001E (Z.X. and Z.M.).
NR 59
TC 23
Z9 26
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2012
VL 32
IS 10
BP 1928
EP 1943
DI 10.1128/MCB.06561-11
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 939TP
UT WOS:000303840100014
PM 22431515
ER
PT J
AU Gegonne, A
Tai, XG
Zhang, JH
Wu, G
Zhu, JJ
Yoshimoto, A
Hanson, J
Cultraro, C
Chen, QR
Guinter, T
Yang, ZH
Hathcock, K
Singer, A
Rodriguez-Canales, J
Tessarollo, L
Mackem, S
Meerzaman, D
Buetow, K
Singer, DS
AF Gegonne, Anne
Tai, Xuguang
Zhang, Jinghui
Wu, Gang
Zhu, Jianjian
Yoshimoto, Aki
Hanson, Jeffrey
Cultraro, Constance
Chen, Qing-Rong
Guinter, Terry
Yang, Zhihui
Hathcock, Karen
Singer, Alfred
Rodriguez-Canales, Jaime
Tessarollo, Lino
Mackem, Susan
Meerzaman, Daoud
Buetow, Ken
Singer, Dinah S.
TI The General Transcription Factor TAF7 Is Essential for Embryonic
Development but Not Essential for the Survival or Differentiation of
Mature T Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; INSERTIONAL MUTAGENESIS; PROMOTER; INITIATION;
ZEBRAFISH; COMPLEX; EMBRYOGENESIS; MACHINERY; SIGNALS; BINDING
AB TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH, and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days postcoitus. Mouse embryonic fibroblasts with TAF7 deleted cease transcription globally and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or for their egress into the periphery. TAF7 deletion in peripheral CD4 T cells affects only a small number of transcripts. However, T cells with TAF7 deleted are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation.
C1 [Gegonne, Anne; Tai, Xuguang; Guinter, Terry; Hathcock, Karen; Singer, Alfred; Singer, Dinah S.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Jinghui; Wu, Gang; Cultraro, Constance; Yang, Zhihui; Meerzaman, Daoud; Buetow, Ken] NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hanson, Jeffrey; Rodriguez-Canales, Jaime] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhu, Jianjian; Yoshimoto, Aki; Mackem, Susan] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Chen, Qing-Rong] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM singerd@mail.nih.gov
OI Rodriguez-Canales, Jaime/0000-0002-0885-2377
FU U.S. National Institutes of Health, the National Cancer Institute and
the Center for Cancer Research
FX This study was supported by the Intramural Research Program of the U.S.
National Institutes of Health, the National Cancer Institute and the
Center for Cancer Research.
NR 39
TC 14
Z9 14
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2012
VL 32
IS 10
BP 1984
EP 1997
DI 10.1128/MCB.06305-11
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 939TP
UT WOS:000303840100018
PM 22411629
ER
PT J
AU Hastings, CE
Fisher, CA
McCabe, MA
AF Hastings, Clare E.
Fisher, Cheryl A.
McCabe, Margaret A.
CA Natl Clin Res Nursing Consortium
TI Clinical research nursing: A critical resource in the national research
enterprise
SO NURSING OUTLOOK
LA English
DT Article
DE Clinical research; Research nursing; Clinical trials; Good Clinical
Practice
AB Translational clinical research has emerged as an important priority for the national research enterprise, with a clearly stated mandate to more quickly deliver prevention strategies, treatments and cures based on scientific innovations to the public. Within this national effort, a lack of consensus persists concerning the need for clinical nurses with expertise and specialized training in study implementation and the delivery of care to research participants. This paper reviews efforts to define and document the role of practicing nurses in implementing studies and coordinating clinical research in a variety of clinical settings, and differentiates this clinical role from the role of nurses as scientists and principal investigators. We propose an agenda for building evidence that having nurses provide and coordinate study treatments and procedures can potentially improve research efficiency, participant safety, and the quality of research data. We also provide recommendations for the development of the emerging specialty of clinical research nursing. Cite this article: Hastings, C. E., Fisher, C. A., & McCabe, M. A. (2012, JUNE). Clinical research nursing: A critical resource in the national research enterprise. Nursing Outlook, 60(3), 149-156. doi:10.1016/j.outlook.2011.10.003.
C1 [Hastings, Clare E.; Fisher, Cheryl A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[McCabe, Margaret A.] Boston Childrens Hosp, Boston, MA USA.
RP Hastings, CE (reprint author), NIH, Ctr Clin, Bldg 10,Room 6-1484,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM chastings@cc.nih.gov
FU Clinical Center, from the National Center for Research Resources, a
component of the National Institutes of Health [MO1-RR02172]; Children's
Hospital Boston, General Clinical Research Center
FX This work was supported in part by the Intramural Research Program of
the NIH, Clinical Center (Hastings and Fisher), Grant Number
MO1-RR02172, from the National Center for Research Resources, a
component of the National Institutes of Health, and the Children's
Hospital Boston, General Clinical Research Center (McCabe).
NR 0
TC 13
Z9 14
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD MAY-JUN
PY 2012
VL 60
IS 3
BP 149
EP 156
DI 10.1016/j.outlook.2011.10.003
PG 8
WC Nursing
SC Nursing
GA 944DK
UT WOS:000304178400008
PM 22172370
ER
PT J
AU Colburn, NH
Bobe, G
Mentor-Marcel, R
Hartman, TJ
Chapkin, R
Lanza, E
Milner, J
Kim, Y
Cross, A
Young, MR
AF Colburn, Nancy H.
Bobe, Gerd
Mentor-Marcel, Roycelynn
Hartman, Terryl J.
Chapkin, Robb
Lanza, Elaine
Milner, John
Kim, Young
Cross, Amanda
Young, Matthew R.
TI DIETARY PREVENTION OF COLON CARCINOGENESIS AND DISCOVERY OF PREDICTIVE
BIOMARKERS
SO PHARMACEUTICAL BIOLOGY
LA English
DT Meeting Abstract
C1 [Colburn, Nancy H.; Bobe, Gerd; Mentor-Marcel, Roycelynn; Young, Matthew R.] NCI, CCR, NIH, Lab Canc Prevent, Frederick, MD 21702 USA.
[Bobe, Gerd; Mentor-Marcel, Roycelynn] NCI, Prevent Oncol Program Canc Prevent Fellowship, Rockville, MD USA.
[Hartman, Terryl J.] Penn State Univ, State Coll, PA USA.
[Chapkin, Robb] Texas A&M Univ, College Stn, TX USA.
[Milner, John; Kim, Young] NCI, Canc Prevent Div, Rockville, MD USA.
[Cross, Amanda] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM colburna@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD MAY
PY 2012
VL 50
IS 5
BP 627
EP 628
PG 2
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 943GN
UT WOS:000304108700265
ER
PT J
AU Hicks, J
Luchsinger, S
Killday, B
Kostikin, P
Muhammad, A
Arnason, J
Berrue, F
Kirby, C
Knagge, K
Zhao, JP
Khan, I
Goedecke, T
Pauli, G
Luo, WB
Benesi, A
Popplewel, W
Gustafson, K
Karakach, T
Burton, I
O'Neil-Johnson, M
Colson, K
AF Hicks, Josh
Luchsinger, Sarah
Killday, Brian
Kostikin, Pavel
Muhammad, Asim
Arnason, John
Berrue, Fabrice
Kirby, Chris
Knagge, Kevin
Zhao, Jianping
Khan, Ikhlas
Goedecke, Tanja
Pauli, Guido
Luo, Wenbin
Benesi, Alan
Popplewel, Wendy
Gustafson, Kirk
Karakach, Tobias
Burton, Ian
O'Neil-Johnson, Mark
Colson, Kim
TI MULTILAB METHOD VALIDATION OF BLUEBERRY LEAF EXTRACT BY NMR: QUALITATIVE
AND QUANTITATIVE
SO PHARMACEUTICAL BIOLOGY
LA English
DT Meeting Abstract
C1 [Hicks, Josh; Luchsinger, Sarah; Killday, Brian; Kostikin, Pavel; Colson, Kim] Bruker BioSpin, Billerica, MA 01821 USA.
[Muhammad, Asim; Arnason, John] U Ottawa, Ottawa, ON K1N 6N5, Canada.
[Berrue, Fabrice] U PEI, Charlottetown, PE C1A 4P3, Canada.
[Kirby, Chris] Agr & Agri Food Canada, Charlottetown, PE C1A 4N6, Canada.
[Knagge, Kevin] Murdock Res Inst, Kannapolis, NC 28081 USA.
[Zhao, Jianping; Khan, Ikhlas] U Mississippi, Oxford, MS 38677 USA.
[Goedecke, Tanja; Pauli, Guido] U Illinois Chicago, Chicago, IL 60680 USA.
[Luo, Wenbin; Benesi, Alan] Penn State U, University Pk, PA 16802 USA.
[Popplewel, Wendy; Gustafson, Kirk] NCI, Frederick, MD 21702 USA.
[Karakach, Tobias; Burton, Ian] NRC, Halifax, NS B3H 3Z1, Canada.
[O'Neil-Johnson, Mark] Sequoia Sci, St Louis, MO 63114 USA.
EM kim.colson@bruker-biospin.com
NR 0
TC 0
Z9 0
U1 2
U2 12
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD MAY
PY 2012
VL 50
IS 5
BP 641
EP 641
PG 1
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 943GN
UT WOS:000304108700306
ER
PT J
AU Pacher, P
AF Pacher, Pal
TI NONPSYCHOACTIVE CONSTITUENTS FROM CANNABIS SATIVA (MARIJUANA):
THERAPEUTIC POTENTIAL IN INFLAMMATORY DISORDERS AND DIABETES
SO PHARMACEUTICAL BIOLOGY
LA English
DT Meeting Abstract
C1 [Pacher, Pal] NIAAA, NIH, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD 20852 USA.
EM pacher@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD MAY
PY 2012
VL 50
IS 5
BP 643
EP 643
PG 1
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 943GN
UT WOS:000304108700312
ER
PT J
AU Rackley, S
Pao, M
Seratti, GF
Gin, N
Rasimas, JJ
Alter, BP
Savage, SA
AF Rackley, Sandra
Pao, Maryland
Seratti, Guillermo F.
Gin, Neelam
Rasimas, J. J.
Alter, Blanche P.
Savage, Sharon A.
TI Neuropsychiatric Conditions Among Patients with Dyskeratosis Congenita:
A Link with Telomere Biology?
SO PSYCHOSOMATICS
LA English
DT Article
ID CELL TRANSPLANTATION; LENGTH; SCHIZOPHRENIA; DISORDERS; MALIGNANCIES;
DISEASE; STRESS; CANCER
AB Background: Dyskeratosis congenita (DC), an inherited bone marrow failure syndrome (IBMFS), is caused by defects in telomere biology, which result in very short germ line telomeres. Telomeres, long nucleotide repeats and a protein complex at chromosome ends, are essential for chromosomal stability. Several association studies suggest that short telomeres are associated with certain psychiatric disorders, including mood disorders and schizophrenia. There are two cases in the literature of schizophrenia and DC occurring as co-morbid conditions. We noted that many patients with DC in our cohort had neuropsychiatric conditions. Methods: Subjects were participants in NCI's IBMFS prospective cohort study. Psychiatric evaluation was incorporated into our clinical assessment in January 2009. Fourteen DC or DC-like patients, including six children, were evaluated in this study through in person interview by either a psychiatrist specialized in psychosomatic medicine or a child and adolescent psychiatrist. Results: Three of the six pediatric subjects and five of the eight adults had a neuropsychiatric condition such as a mood, anxiety, or adjustment disorder, intellectual disability, attention deficit hyperactivity disorder, or pervasive developmental disorders. The lifetime occurrence of any of these disorders in our study was 83% in pediatric subjects and 88% in adults. Notably, the literature reports neuropsychiatric conditions in 25% and 38% in chronically ill children and adults, respectively. Conclusion: This pilot study suggests that patients with DC may have higher rates of neuropsychiatric conditions than the general population or other chronically ill individuals. This potential link between very short telomeres and neuropsychiatric conditions warrants further study. (Psychosomatics 2012; 53:230-235)
C1 [Seratti, Guillermo F.; Gin, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Rackley, Sandra] Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC 20010 USA.
[Pao, Maryland] NIMH, Off Clin Director, Bethesda, MD 20892 USA.
[Rasimas, J. J.] Penn State Coll Med, Dept Psychiat, Hershey, PA USA.
[Rasimas, J. J.] NIMH, Expt & Therapeut Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7018, Rockville, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU Westat, Inc. (NIH) [N02-CP-11019, N02-CP-65504, N02-CP-65501]; National
Cancer Institute; National Institute of Mental Health, National
Institutes of Health
FX The authors thank the patients and families who have generously
contributed to their understanding of dyskeratosis congenita and
telomere biology disorders. Lisa Leathwood, RN, Westat, Inc. (NIH
contracts N02-CP-11019, N02-CP-65504 and N02-CP-65501) provided
outstanding study support. This work was funded by the intramural
research programs of the National Cancer Institute and the National
Institute of Mental Health, National Institutes of Health.
NR 27
TC 8
Z9 9
U1 1
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD MAY-JUN
PY 2012
VL 53
IS 3
BP 230
EP 235
PG 6
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 941MV
UT WOS:000303968200004
PM 22458992
ER
PT J
AU Wallwork, RS
Fortgang, R
Hashimoto, R
Weinberger, DR
Dickinson, D
AF Wallwork, R. S.
Fortgang, R.
Hashimoto, R.
Weinberger, D. R.
Dickinson, D.
TI Searching for a consensus five-factor model of the Positive and Negative
Syndrome Scale for schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Symptoms; Cognition; PANSS
ID CONFIRMATORY FACTOR-ANALYSIS; ONSET SCHIZOPHRENIA; SYMPTOM DIMENSIONS;
PANSS; VALIDATION; PSYCHOSIS; STABILITY; VALIDITY; RISK
AB Although the developers of the Positive and Negative Syndrome Scale (PANSS) grouped items into three subscales, factor analyses indicate that a five-factor model better characterizes PANSS data. However, lack of consensus on which model to use limits the comparability of PANSS variables across studies. We counted "votes" from published factor analyses to derive consensus models. One of these combined superior fit in our Caucasian sample (n=458, CFI=.970), and in distinct Japanese sample (n=164, CFI=.964), relative to the original three-subscale model, with a sorting of items into factors that was highly consistent across the studies reviewed. Published by Elsevier B.V.
C1 [Wallwork, R. S.; Fortgang, R.; Weinberger, D. R.; Dickinson, D.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Hashimoto, R.] Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka, Japan.
[Weinberger, D. R.] Japan Sci & Technol Agcy JST, CREST, Saitama, Japan.
[Weinberger, D. R.] Johns Hopkins Med Ctr, Lieber Inst Brain Dev, Baltimore, MD USA.
RP Dickinson, D (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 7SE-5335, Bethesda, MD 20892 USA.
EM Dwight.Dickinson@nih.gov
RI Hashimoto, Ryota/P-8572-2014
OI Hashimoto, Ryota/0000-0002-5941-4238
FU National Institute of Mental Health
FX Funding for this study was provided by the Intramural Research Program
of the National Institute of Mental Health; the NIMH IRP had no further
role in study design; in the collection, analysis and interpretation of
data; in the writing of the report; and in the decision to submit the
paper for publication.
NR 42
TC 122
Z9 124
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAY
PY 2012
VL 137
IS 1-3
BP 246
EP 250
DI 10.1016/j.schres.2012.01.031
PG 5
WC Psychiatry
SC Psychiatry
GA 941AI
UT WOS:000303933800040
PM 22356801
ER
PT J
AU Geldmacher, C
Koup, RA
AF Geldmacher, Christof
Koup, Richard A.
TI Pathogen-specific T cell depletion and reactivation of opportunistic
pathogens in HIV infection
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID SIMIAN IMMUNODEFICIENCY VIRUS; MUCOSAL HOMING RECEPTOR; HUMAN
LYMPHOID-TISSUE; HUMAN-PAPILLOMAVIRUS; SIV INFECTION; MEMORY CD4(+);
INTEGRIN ALPHA(4)BETA(7); ANTIRETROVIRAL THERAPY;
GASTROINTESTINAL-TRACT; DISEASE PROGRESSION
AB During HIV infection, it is unclear why different opportunistic pathogens cause disease at different CD4 T cell count thresholds. Early work has shown that CD4 T cell depletion is influenced both by cellular activation status and expression of viral entry receptors. More recently, functional characteristics; of the CD4 T cells, such as cytokine and chemokine production, have also been shown to influence cellular susceptibility to HIV. Here, we examine how functional differences in pathogen-specific CD4 T cells could lead to their differential loss during HIV infection. This may have implications for when different opportunistic infections occur, and a better understanding of the mechanisms for functional imprinting of antigen-specific T cells may lead to improvements in design of vaccines against HIV and opportunistic pathogens.
C1 [Geldmacher, Christof] Univ Munich LMU, Div Infect Dis & Trop Med, Med Ctr, Munich, Germany.
[Geldmacher, Christof] Univ Munich LMU, Natl Ctr Infect Dis Germany, Med Ctr, Munich, Germany.
[Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Geldmacher, C (reprint author), Univ Munich LMU, Div Infect Dis & Trop Med, Med Ctr, Munich, Germany.
EM geldmacher@lrz.uni-muenehen.de
FU Intramural NIH HHS [ZIA AI005014-10, ZIA AI005015-10]
NR 92
TC 14
Z9 14
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD MAY
PY 2012
VL 33
IS 5
BP 207
EP 214
DI 10.1016/j.it.2012.01.011
PG 8
WC Immunology
SC Immunology
GA 942UV
UT WOS:000304076400002
PM 22398371
ER
PT J
AU Manolio, TA
Weis, BK
Cowie, CC
Hoover, RN
Hudson, K
Kramer, BS
Berg, C
Collins, R
Ewart, W
Gaziano, JM
Hirschfeld, S
Marcus, PM
Masys, D
McCarty, CA
McLaughlin, J
Patel, AV
Peakman, T
Pedersen, NL
Schaefer, C
Scott, JA
Sprosen, T
Walport, M
Collins, FS
AF Manolio, Teri A.
Weis, Brenda K.
Cowie, Catherine C.
Hoover, Robert N.
Hudson, Kathy
Kramer, Barnett S.
Berg, Chris
Collins, Rory
Ewart, Wendy
Gaziano, J. Michael
Hirschfeld, Steven
Marcus, Pamela M.
Masys, Daniel
McCarty, Catherine A.
McLaughlin, John
Patel, Alpa V.
Peakman, Tim
Pedersen, Nancy L.
Schaefer, Catherine
Scott, Joan A.
Sprosen, Timothy
Walport, Mark
Collins, Francis S.
TI New Models for Large Prospective Studies: Is There a Better Way?
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE cohort studies; epidemiology; prospective studies
ID GENOME-WIDE ASSOCIATION; PROSPECTIVE COHORT; DESIGN; GENES; FEASIBILITY;
RECRUITMENT; ENVIRONMENT; PROSTATE
AB Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the "UK Biobank," which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which "process" expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.
C1 [Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Weis, Brenda K.; Kramer, Barnett S.] NIH, Div Program Coordinat Planning & Strateg Initiat, Bethesda, MD 20892 USA.
[Cowie, Catherine C.] NIDDK, Bethesda, MD USA.
[Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hudson, Kathy; Collins, Francis S.] NIH, Off Director, Bethesda, MD 20892 USA.
[Berg, Chris] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Collins, Rory] Univ Oxford, Epidemiol Studies Unit, Oxford, England.
[Ewart, Wendy] MRC, London, England.
[Gaziano, J. Michael] Boston VA Med Ctr, Boston, MA USA.
[Hirschfeld, Steven] NICHHD, Bethesda, MD 20892 USA.
[Marcus, Pamela M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Masys, Daniel] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA.
[McCarty, Catherine A.] Essentia Inst Hlth Res, Duluth, MN USA.
[McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada.
[McLaughlin, John] Ontario Inst Canc Res, Toronto, ON, Canada.
[Patel, Alpa V.] Amer Canc Soc, Canc Prevent Study 3, Atlanta, GA 30329 USA.
[Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Schaefer, Catherine] Kaiser Permanente Program Genes Environm & Hlth, Oakland, CA USA.
[Scott, Joan A.] Natl Coalit Hlth Profess Educ Genet, Washington, DC USA.
[Sprosen, Timothy] Univ London Imperial Coll Sci Technol & Med, London, England.
[Walport, Mark] Wellcome Trust Res Labs, London, England.
RP Manolio, TA (reprint author), NHGRI, Off Populat Genom, 5635 Fishers Lane,Suite 3058,MSC 9307, Bethesda, MD 20892 USA.
EM manolio@nih.gov
RI McLaughlin, John/E-4577-2013;
OI Walport, Mark/0000-0001-7220-5273
FU Medical Research Council [MC_QA137853]
NR 29
TC 43
Z9 45
U1 1
U2 17
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 MAY 1
PY 2012
VL 175
IS 9
BP 859
EP 866
DI 10.1093/aje/kwr453
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 937IU
UT WOS:000303653000001
PM 22411865
ER
PT J
AU Tsilidis, KK
Travis, RC
Appleby, PN
Allen, NE
Lindstrom, S
Schumacher, FR
Cox, D
Hsing, AW
Ma, J
Severi, G
Albanes, D
Virtamo, J
Boeing, H
Bueno-de-Mesquita, HB
Johansson, M
Quiros, JR
Riboli, E
Siddiq, A
Tjonneland, A
Trichopoulos, D
Tumino, R
Gaziano, JM
Giovannucci, E
Hunter, DJ
Kraft, P
Stampfer, MJ
Giles, GG
Andriole, GL
Berndt, SI
Chanock, SJ
Hayes, RB
Key, TJ
AF Tsilidis, Konstantinos K.
Travis, Ruth C.
Appleby, Paul N.
Allen, Naomi E.
Lindstrom, Sara
Schumacher, Fredrick R.
Cox, David
Hsing, Ann W.
Ma, Jing
Severi, Gianluca
Albanes, Demetrius
Virtamo, Jarmo
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Johansson, Mattias
Ramon Quiros, J.
Riboli, Elio
Siddiq, Afshan
Tjonneland, Anne
Trichopoulos, Dimitrios
Tumino, Rosario
Gaziano, J. Michael
Giovannucci, Edward
Hunter, David J.
Kraft, Peter
Stampfer, Meir J.
Giles, Graham G.
Andriole, Gerald L.
Berndt, Sonja I.
Chanock, Stephen J.
Hayes, Richard B.
Key, Timothy J.
TI Interactions Between Genome-wide Significant Genetic Variants and
Circulating Concentrations of Insulin-like Growth Factor 1, Sex
Hormones, and Binding Proteins in Relation to Prostate Cancer Risk in
the National Cancer Institute Breast and Prostate Cancer Cohort
Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE gene-environment interaction; gonadal steroid hormones; insulin-like
growth factor binding protein 3; insulin-like growth factor I; molecular
epidemiology; prostatic neoplasms
ID STEROID-HORMONES; FACTOR-I; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; FREE
TESTOSTERONE; SUBSEQUENT RISK; SERUM ANDROGENS; ASSOCIATION; 8Q24;
IDENTIFICATION
AB Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.
C1 [Tsilidis, Konstantinos K.; Travis, Ruth C.; Appleby, Paul N.; Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Lindstrom, Sara; Albanes, Demetrius; Giovannucci, Edward; Kraft, Peter; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cox, David] Ctr Leon Berard, Lyon Canc Res Ctr, INSERM U1052, F-69373 Lyon, France.
[Cox, David; Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Hsing, Ann W.; Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ma, Jing; Giovannucci, Edward; Hunter, David J.; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Ma, Jing; Gaziano, J. Michael; Giovannucci, Edward; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA.
[Severi, Gianluca; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Severi, Gianluca; Giles, Graham G.] Univ Melbourne, Ctr Mol Genet Environm & Analyt Epidemiol, Melbourne, Vic, Australia.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Ramon Quiros, J.] Publ Hlth & Hlth Planning Directorate, Asturias, Spain.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy.
[Tumino, Rosario] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Lindstrom, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA.
RP Tsilidis, KK (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
EM kostas.tsilidis@ceu.ox.ac.uk
RI Cox, David/A-2023-2009; Albanes, Demetrius/B-9749-2015
OI Cox, David/0000-0002-2152-9259;
FU US National Cancer Institute [U01-CA98233-07, U01-CA98710-06,
U01-CA98216-06, U01-CA98758-07]; US National Institutes of Health;
Australian National Health and Medical Research Council [209057, 251553,
450104]; Cancer Research UK
FX This study was supported by the US National Cancer Institute (grant
U01-CA98233-07 to Dr. David J. Hunter, grant U01-CA98710-06 to Dr.
Michael J. Thun, grant U01-CA98216-06 to Drs. Elio Riboli and Rudolf
Kaaks, and grant U01-CA98758-07 to Dr. Brian E. Henderson) and by a
grant from the Intramural Research Program of the US National Institutes
of Health. The Melbourne Collaborative Cohort Study was supported by
grants 209057, 251553, and 450104 from the Australian National Health
and Medical Research Council and by infrastructure provided by Cancer
Council Victoria. Dr. Konstantinos K. Tsilidis was supported by Cancer
Research UK.
NR 42
TC 9
Z9 9
U1 0
U2 10
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 MAY 1
PY 2012
VL 175
IS 9
BP 926
EP 935
DI 10.1093/aje/kwr423
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 937IU
UT WOS:000303653000010
PM 22459122
ER
PT J
AU Williams, PL
Seage, GR
Van Dyke, RB
Siberry, GK
Griner, R
Tassiopoulos, K
Yildirim, C
Read, JS
Huo, YL
Hazra, R
Jacobson, DL
Mofenson, LM
Rich, K
AF Williams, Paige L.
Seage, George R., III
Van Dyke, Russell B.
Siberry, George K.
Griner, Raymond
Tassiopoulos, Katherine
Yildirim, Cenk
Read, Jennifer S.
Huo, Yanling
Hazra, Rohan
Jacobson, Denise L.
Mofenson, Lynne M.
Rich, Kenneth
CA Pediat HIV AIDS Cohort Study
TI A Trigger-based Design for Evaluating the Safety of In Utero
Antiretroviral Exposure in Uninfected Children of Human Immunodeficiency
Virus-Infected Mothers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE antiretroviral; asymptotic relative efficiency; HIV-exposed; infants;
outcome-dependent sampling; safety; surveillance
ID PERSISTENT MITOCHONDRIAL DYSFUNCTION; MEDICATION-RELATED HARM; PERINATAL
EXPOSURE; UNITED-STATES; HIV; TRANSMISSION; WOMEN; INFANTS; PREGNANCY;
DRUGS
AB The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.
C1 [Williams, Paige L.; Seage, George R., III; Griner, Raymond; Tassiopoulos, Katherine; Yildirim, Cenk; Huo, Yanling; Jacobson, Denise L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Seage, George R., III; Tassiopoulos, Katherine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Van Dyke, Russell B.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
[Siberry, George K.; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Read, Jennifer S.] Dept Hlth & Human Serv, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Off Secretary, Washington, DC USA.
[Rich, Kenneth] Univ Illinois, Chicago, IL USA.
RP Williams, PL (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 665 Huntington Ave,FXB-607, Boston, MA 02115 USA.
EM paige@sdac.harvard.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Deafness and Other Communication Disorders;
National Heart, Lung, and Blood Institute; National Institute of
Neurological Disorders and Stroke; National Institute on Alcohol Abuse
and Alcoholism, through Harvard University School of Public Health [U01
HD052102-04]; Tulane University School of Medicine [U01 HD052104-01]
FX The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, with
co-funding from the National Institute of Allergy and Infectious
Diseases, the National Institute on Drug Abuse, the National Institute
of Mental Health, the National Institute of Deafness and Other
Communication Disorders, the National Heart, Lung, and Blood Institute,
the National Institute of Neurological Disorders and Stroke, and the
National Institute on Alcohol Abuse and Alcoholism, through cooperative
agreements with the Harvard University School of Public Health (U01
HD052102-04) (Principal Investigator: George Seage; Project Director:
Julie Alperen) and the Tulane University School of Medicine (U01
HD052104-01) (Principal Investigator: Russell Van Dyke; Co-Principal
Investigator: Kenneth Rich; Project Director: Patrick Davis). Data
management services were provided by Frontier Science and Technology
Research Foundation (Principal Investigator: Suzanne Siminski), and
regulatory services and logistical support were provided by Westat, Inc
(Principal Investigator: Julie Davidson).
NR 40
TC 17
Z9 17
U1 0
U2 4
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 MAY 1
PY 2012
VL 175
IS 9
BP 950
EP 961
DI 10.1093/aje/kwr401
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 937IU
UT WOS:000303653000012
PM 22491086
ER
PT J
AU Avila, N
Crocker, M
Millo, C
Niyyati, M
VanRyzin, C
Dwyer, A
Merke, D
AF Avila, N.
Crocker, M.
Millo, C.
Niyyati, M.
VanRyzin, C.
Dwyer, A.
Merke, D.
TI Ectopic Adrenal Rest Tissue in Patients With Congenital Adrenal
Hyperplasia: Imaging Characteristics and Localization
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Roentgen-Ray-Society
CY APR 29-MAY 04, 2012
CL Vancouver, CANADA
SP Amer Roentgen Ray Soc
C1 [Avila, N.] Washington DC Vet Affairs Med Ctr, Washington, DC USA.
[Avila, N.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Crocker, M.] Childrens Hosp, Boston, MA 02115 USA.
[Millo, C.; Niyyati, M.; VanRyzin, C.; Merke, D.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[VanRyzin, C.; Merke, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM nilo.avila@va.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY
PY 2012
VL 198
IS 5
SU S
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 937OI
UT WOS:000303667400719
ER
PT J
AU Linguraru, M
Sandberg, J
Petrick, N
Summers, R
AF Linguraru, M.
Sandberg, J.
Petrick, N.
Summers, R.
TI Hepatic Volumetric Nomograms From Automated Analysis of Abdominal CT
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Roentgen-Ray-Society
CY APR 29-MAY 04, 2012
CL Vancouver, CANADA
SP Amer Roentgen Ray Soc
C1 [Linguraru, M.; Sandberg, J.; Summers, R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Petrick, N.] Food & Drug Adm Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM rms@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2012
VL 198
IS 5
SU S
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 937OI
UT WOS:000303667400126
ER
PT J
AU Liu, J
Hua, J
Yao, J
White, J
Summers, R
AF Liu, J.
Hua, J.
Yao, J.
White, J.
Summers, R.
TI Computer-Aided Detection of Lymphadenopathy in Contrast-Enhanced
Abdominal CT
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Roentgen-Ray-Society
CY APR 29-MAY 04, 2012
CL Vancouver, CANADA
SP Amer Roentgen Ray Soc
C1 [Liu, J.; Hua, J.; Yao, J.; White, J.; Summers, R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM rms@nih.gov
NR 0
TC 0
Z9 0
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 MAY
PY 2012
VL 198
IS 5
SU S
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 937OI
UT WOS:000303667400456
ER
PT J
AU Valle-Onate, R
Ward, MM
Kerr, GS
AF Valle-Onate, Rafael
Ward, Michael M.
Kerr, Gail S.
TI Physical Therapy and Surgery
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 9th Annual Research and Education Meeting of Spondyloarthritis Research
and Treatment Network (SPARTAN)
CY JUL 29-30, 2011
CL Portland, OR
DE Total hip arthroplasty; Physical therapy; Ankylosing spondylitis
ID TOTAL HIP-ARTHROPLASTY; CAUDA-EQUINA SYNDROME; ANKYLOSING-SPONDYLITIS;
HETEROTOPIC OSSIFICATION; ECTOPIC OSSIFICATION; REPLACEMENT;
INVOLVEMENT; PREVENTION; REHABILITATION; RADIOTHERAPY
AB Physical therapy and orthopedic surgery are important components in the treatment of ankylosing spondylitis (AS). Supervised physical therapy is more effective than individual or unsupervised exercise in improving symptoms, but controlled trials suggest that combined inpatient and outpatient therapy provides the greatest improvement. Recommendations for exercise are universal, but the best types and sequence of therapies are not known. Total hip replacement is the surgery most commonly performed for AS, with good long-term implant survival. Heterotopic ossification may occur no more frequently after hip replacement in patients with AS than in patients with other diseases. Corrective spinal surgery is rarely performed and requires specialized centers and experienced surgeons.
C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20893 USA.
[Valle-Onate, Rafael] Univ Sabana, Mil Hosp Sch Med, Bogota, Colombia.
[Kerr, Gail S.] Vet Affairs Med Ctr, Dept Med Serv, Washington, DC 20422 USA.
RP Ward, MM (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20893 USA.
EM wardm1@mail.nih.gov
FU Intramural NIH HHS [Z01 AR041153-03]
NR 42
TC 2
Z9 2
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD MAY
PY 2012
VL 343
IS 5
BP 353
EP 356
DI 10.1097/MAJ.0b013e3182514080
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 937OH
UT WOS:000303667300004
PM 22543536
ER
PT J
AU Tse, SML
Burgos-Vargas, R
Colbert, RA
AF Tse, Shirley M. L.
Burgos-Vargas, Ruben
Colbert, Robert A.
TI Juvenile Spondyloarthritis Treatment Recommendations
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 9th Annual Research and Education Meeting of Spondyloarthritis Research
and Treatment Network (SPARTAN)
CY JUL 29-30, 2011
CL Portland, OR
DE Juvenile spondyloarthritis; Enthesitis-related arthritis; Axial
ID SOCIETY CLASSIFICATION CRITERIA; ANTITUMOR NECROSIS FACTOR;
PLACEBO-CONTROLLED TRIAL; ANKYLOSING-SPONDYLITIS; DOUBLE-BLIND;
RADIOGRAPHIC PROGRESSION; AXIAL SPONDYLOARTHRITIS; RHEUMATOID-ARTHRITIS;
IDIOPATHIC ARTHRITIS; RANDOMIZED-TRIAL
AB No specific recommendations for the treatment of juvenile spondyloarthritis have been established. Important differences exist in how spondyloarthritis begins and progresses in children and adults, supporting the need for pediatric-specific recommendations. Recently published recommendations for the treatment of juvenile arthritis consider children with sacroiliitis in a separate group and allow for more accelerated institution of a tumor necrosis factor inhibitor depending on disease activity and prognostic factors that derive primarily from studies of other forms of juvenile arthritis. There is a need to develop measures of disease activity and prognosis specific for juvenile spondyloarthritis that reflect spinal disease, as well as other major clinical features, such as enthesitis, before significant progress can be made in this area.
C1 [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20893 USA.
[Tse, Shirley M. L.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Burgos-Vargas, Ruben] Hosp Gen Mexico City, Mexico City, DF, Mexico.
RP Colbert, RA (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20893 USA.
EM colbertra@mac.com
FU Intramural NIH HHS [ZIA AR041184-02]
NR 41
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD MAY
PY 2012
VL 343
IS 5
BP 367
EP 370
DI 10.1097/MAJ.0b013e3182514043
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 937OH
UT WOS:000303667300008
PM 22543540
ER
PT J
AU Reveille, JD
Ximenes, A
Ward, MM
AF Reveille, John D.
Ximenes, Antonio
Ward, Michael M.
TI Economic Considerations of the Treatment of Ankylosing Spondylitis
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 9th Annual Research and Education Meeting of Spondyloarthritis Research
and Treatment Network (SPARTAN)
CY JUL 29-30, 2011
CL Portland, OR
DE Spondyloarthritis; Ankylosing spondylitis; Psoriatic arthritis;
Economics; Anti-TNF treatment
ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; TOTAL
HIP-ARTHROPLASTY; LOW-DOSE INFLIXIMAB; COST-OF-ILLNESS;
RHEUMATOID-ARTHRITIS; WORK DISABILITY; RISK-FACTORS; DOUBLE-BLIND;
ETANERCEPT
AB Ankylosing spondylitis (AS) is associated with both significant direct and indirect costs, which vary by country, and have generally increased dramatically since the introduction of anti-tumor necrosis factor therapy. The cost-effectiveness of biologic agents is controversial, although cost-effectiveness studies need to consider the potential impact of anti-tumor necrosis factor treatments on work ability. Alternatives to reduce costs associated with biologics have been examined, including on-demand dosing and lower dose alternatives. Other treatment measures, such as total hip arthroplasty and physical therapy, are also effective in reducing pain and improving function in patients with AS, although the optimal type or combination of physical therapy treatment modalities, the optimal frequency and duration of treatment and whether therapy is equally effective in stable disease and uncontrolled AS need to be determined. No studies have examined differences in patient outcomes based on subspecialty care. Establishing an evidence base for these questions would help inform policy decisions to design the most cost-effective measures to treat AS.
C1 [Reveille, John D.] Univ Texas Houston Hlth Sci Ctr, Div Rheumatol, Houston, TX 77030 USA.
[Ximenes, Antonio] Hosp Geral Goiania, Div Rheumatol, Goiania, Go, Brazil.
[Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Reveille, JD (reprint author), Univ Texas Houston Hlth Sci Ctr, Div Rheumatol, MSB 5-270,6431 Fannin, Houston, TX 77030 USA.
EM john.d.reveille@uth.tmc.edu
FU Intramural NIH HHS [ZIA AR041153-07]; NIAID NIH HHS [1U01AI090909-01,
U01 AI090909]; NIAMS NIH HHS [P01 AR052915]; PHS HHS [P01-052915-01]
NR 42
TC 13
Z9 14
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD MAY
PY 2012
VL 343
IS 5
BP 371
EP 374
DI 10.1097/MAJ.0b013e3182514093
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 937OH
UT WOS:000303667300009
PM 22543541
ER
PT J
AU Geller, B
Luby, JL
Joshi, P
Wagner, KD
Emslie, G
Walkup, JT
Axelson, DA
Bolhofner, K
Robb, A
Wolf, DV
Riddle, MA
Birmaher, B
Nusrat, N
Ryan, ND
Vitiello, B
Tillman, R
Lavori, P
AF Geller, Barbara
Luby, Joan L.
Joshi, Paramjit
Wagner, Karen Dineen
Emslie, Graham
Walkup, John T.
Axelson, David A.
Bolhofner, Kristine
Robb, Adelaide
Wolf, Dwight V.
Riddle, Mark A.
Birmaher, Boris
Nusrat, Nasima
Ryan, Neal D.
Vitiello, Benedetto
Tillman, Rebecca
Lavori, Philip
TI A Randomized Controlled Trial of Risperidone, Lithium, or Divalproex
Sodium for Initial Treatment of Bipolar I Disorder, Manic or Mixed
Phase, in Children and Adolescents
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID SSRI-RESISTANT DEPRESSION; PLACEBO-CONTROLLED TRIAL; GLOBAL ASSESSMENT
SCALE; DOUBLE-BLIND; KIDDIE SCHEDULE; RISK; ANTIDEPRESSANTS;
SCHIZOPHRENIA; PHENOMENOLOGY; METAANALYSIS
AB Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents.
Objective: To investigate which medication to administer first to antimanic medication-naive subjects.
Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6- to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5US sites from 2003 to 2008 into a controlled, randomized, no-patientchoice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments.
Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 mu g/mL), and risperidone (4-6 mg).
Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents.
Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics: 100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) mu g/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; chi(2)(1) = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; chi(2)(1) = 28.3, P < .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (chi(2)(1) = 6.4, P =. 011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F-1,F-212 = 45.5, P < .001; F-1,F-212 = 39.1, P < .001; and F-1,F-213 = 191.4, P < .001, respectively) and vs divalproex sodium (F-1,F-212 = 34.7, P <.001; F-1,F-212 = 45.3, P <.001; and F-1,F-213 = 209.4, P < .001, respectively). The thyrotropin level increased in subjects taking lithium (t(62) = 11.3, P < .001).
Conclusions: Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects.
C1 [Geller, Barbara; Luby, Joan L.; Bolhofner, Kristine; Tillman, Rebecca] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
[Joshi, Paramjit; Robb, Adelaide; Nusrat, Nasima] Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC 20010 USA.
[Wagner, Karen Dineen; Wolf, Dwight V.] Univ Texas Med Branch, Dept Psychiat, Galveston, TX USA.
[Emslie, Graham] Univ Texas SW, Dept Psychiat, Dallas, TX USA.
[Walkup, John T.; Riddle, Mark A.] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Axelson, David A.; Birmaher, Boris; Ryan, Neal D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Lavori, Philip] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
RP Geller, B (reprint author), Washington Univ, Dept Psychiat, 660 S Euclid, St Louis, MO 63110 USA.
EM gellerb@wustl.edu
FU NIMH [U01 MH064846, U01 MH064850, U01 MH064851, U01 MH064868, U01
MH064869, U01 MH064887, U01 MH064911, R01 MH051481]; National Alliance
for Research on Schizophrenia and Depression; CHADS; Biobehavioral
Diagnostics, Inc; Eli Lilly; Forest; GlaxoSmithKline; Shire; Somerset;
Bristol Meyers Squibb; McNeil Pediatrics; Merck Scherring Plough;
Janssen; Sepracor; Supernus; Otsuka; Pfizer; Johnson and Johnson;
Merck/Scherring Plough
FX Dr Geller reports the following for the work under consideration: a
grant from NIMH; support for travel to meetings from NIMH; payment for
writing or reviewing the manuscript from NIMH; and provision of writing
assistance, equipment, or administrative support from NIMH. Dr Geller
also reports the following from outside the submitted work: consultancy
for NIMH and the US Food and Drug Administration (FDA) Federal Advisory
Committees; employment at Washington University in St Louis, Missouri;
grants from NIMH; payment for lectures from Vanderbilt University and
the International Review of Bipolar Disorder; payment for manuscript
preparation from NIMH; royalties from Guilford Press; travel,
accommodations, and meeting expenses from NIMH and FDA for service on
Federal Advisory Committees; payment from Massachusetts Medical Society
for Journal Watch in Psychiatry Associate Editorship. Dr Luby reports
the following for the work under consideration: grant from NIMH and
provision of medicines from Abbott. Dr Luby also reports the following
from outside the submitted work: employment at Washington University
School of Medicine in St Louis, Missouri; grants/grants pending from
NIMH, National Alliance for Research on Schizophrenia and Depression,
and CHADS; and royalties from Guilford Press. Dr Joshi reports the
following from the work under consideration: a grant from NIMH; support
for travel to meetings from NIMH; provision of medicines from Abbott. Dr
Joshi also reports the following from outside the submitted work:
employment at Children's National Medical Center in Washington, DC. Dr
Wagner reports the following from the work under consideration: grant
from NIMH and provision of medicines from Abbott. Dr Wagner also reports
the following from outside the submitted work: consultancy for Forest,
American Institute of Biological Sciences, Krog and Partners, and
National Institutes of Health; employment at University of Texas Medical
Branch in Galveston; payment for lectures from American Psychiatric
Association, Letters and Sciences, American Society of Clinical
Psychopharmacology, Toledo Hospital, American Academy of Child and
Adolescent Psychiatry, Madison Institute of Medicine, Mexican
Psychiatric Association, Contemporary Forums, Doctors Hospital at
Renaissance, CME LLC, Nevada Psychiatric Association, and Quantia
Communications; payment for manuscript preparation from Guilford
Publications, Health and Wellness Education Partners, American
Psychiatric Publishing Inc, Springer Publishing, CMP Medica, UBM Medica,
and Wolters Kluver Health; payment from Physician's Postgraduate Press,
Inc, for serving as deputy editor of the Journal of Clinical Psychiatry.
Dr Wagner also sits on the Scientific Advisory Board of the Child and
Adolescent Bipolar Foundation and on the Scientific Advisory Board of
the Depression and Bipolar Support Alliance. Dr Emslie reports the
following from the work under consideration: a grant from NIMH and
provision of medicines from Abbott. Dr Emslie also reports the following
from outside the submitted work: consultancy for Biobehavioral
Diagnostics, Inc, Eli Lilly, Forest, GlaxoSmithKline, Pfizer, Shire,
Validus, and Wyeth; employment at University of Texas Southwestern
Medical Center; grants/grants pending from NIMH, Biobehavioral
Diagnostics, Inc, Eli Lilly, Forest, GlaxoSmithKline, Shire, and
Somerset; payment for lectures, including service on speakers bureaus
from Forest; and receiving payment for manuscript preparation from
British Medical Journal Online.; Dr Walkup reports the following for the
work under consideration: a grant from NIMH; support for travel to
meetings from NIMH; and provision of medicines from Abbott. Dr Axelson
reports the following for the work under consideration: a grant from
NIMH. Ms Bolhofner reports the following for the work under
consideration: a grant from NIMH. Ms Bolhofner also reports the
following from outside the submitted work: employment at Washington
University in St Louis, Missouri, and grants from NIMH. Dr Robb reports
the following for the work under consideration: a grant from NIMH;
support for travel to meetings from NIMH; provision of medicines from
Abbott; and payment for serving as clinical pharmacologist for the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. Dr Robb also reports the following from outside the
submitted work: board membership at Lilly, Bristol Myers Squibb, Otsuka,
Shinogi, and McNeil Pediatrics; consultancy for Lundbeck; employment at
Children's National Medical Center; expert testimony for a case on
antipsychotic use; grants/grants pending from Bristol Meyers Squibb,
McNeil Pediatrics, Merck Scherring Plough, GlaxoSmithKline, Janssen,
Sepracor, Supernus, Otsuka, Pfizer, Johnson and Johnson, and Forest;
payment for service on speakers bureaus from Bristol Myers Squibb,
Lilly, and McNeil Pediatrics; royalties from Epocrates; payment for
development of education presentations from University of Minnesota,
American Academy of Child & Adolescent Psychiatry, and American Academy
of Pediatrics; stock/stock options from Lilly, Pfizer, Johnson and
Johnson, GlaxoSmithKline, and 3M. Dr Robb also sits on the Children and
Adults with Attention-Deficit/Hyperactivity Disorder professional
advisory board and program committee for the American Psychiatric
Association annual meeting, and her husband sits on American Epilepsy
Society Board and Scientific Committee for Child Neurology Society. Dr
Wolf reports the following for the work under consideration: a grant
from NIMH. Dr Riddle reports the following for the work under
consideration: a grant from NIMH and provision of medicines from Abbott.
Dr Riddle also reports the following from outside the submitted work:
employment at Johns Hopkins University; expert testimony for Teva
Canada; and receiving aripiprazole for an NIMH study. Dr Birmaher
reports the following for the work under consideration: a grant from
NIMH. Dr Birmaher also reports the following from outside the submitted
work: consultancy for Schering Plough, Dey Pharma, Forest, and Jazz
Pharmaceuticals; and royalties from Random House and Lippincott Williams
and Wilkins. Dr Nusrat reports the following for the work under
consideration: a grant from NIMH; support for travel to meetings from
NIMH; and provision of medicines from Abbott. Dr Nusrat also reports the
following from outside the submitted work: employment at Children's
National Medical Center and grants/grants pending from Merck/Scherring
Plough, GlaxoSmithKline, Janssen, Sepracor, Supernus, Otsuka, Pfizer,
Johnson and Johnson, and Forest. Dr Ryan reports the following for the
work under consideration: a grant from NIMH; support for travel to
meetings from NIMH; and provision of medicines from Abbott. Dr Ryan also
reports the following from outside the submitted work: employment at the
University of Pittsburgh and the University of Pittsburgh Medical
Center. Ms Tillman reports the following for the work under
consideration: a grant from NIMH and payment for writing or reviewing
the manuscript from NIMH.; Ms Tillman also reports the following from
outside the submitted work: employment at Washington University in St
Louis and receiving travel/accommodations/meeting expenses from NIMH. Dr
Lavori reports the following for the work under consideration: a grant
from NIMH.; This work was supported by NIMH grants U01 MH064846, U01
MH064850, U01 MH064851, U01 MH064868, U01 MH064869, U01 MH064887, U01
MH064911, and R01 MH051481.
NR 37
TC 69
Z9 69
U1 5
U2 25
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 MAY
PY 2012
VL 69
IS 5
BP 515
EP 528
DI 10.1001/archgenpsychiatry.2011.1508
PG 14
WC Psychiatry
SC Psychiatry
GA 937QB
UT WOS:000303672000011
PM 22213771
ER
PT J
AU Lipsky, LM
Iannotti, RJ
AF Lipsky, Leah M.
Iannotti, Ronald J.
TI Associations of Television Viewing With Eating Behaviors in the 2009
Health Behaviour in School-aged Children Study
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; BODY-MASS INDEX; SOFT DRINK CONSUMPTION;
SEDENTARY LIFE-STYLE; FAST-FOOD INTAKE; PHYSICAL-ACTIVITY;
UNITED-STATES; NATIONAL-HEALTH; ENERGY-INTAKE; INTERDISCIPLINARY
INTERVENTION
AB Objective: To examine associations of television viewing with eating behaviors in a representative sample of US adolescents.
Design: Cross-sectional survey.
Setting: Public and private schools in the United States during the 2009-2010 school year.
Participants: A total of 12 642 students in grades 5 to 10 (mean [SD] age, 13.4[0.09] years; 86.5% participation).
Main Exposures: Television viewing (hours per day) and snacking while watching television (days per week).
Main Outcome Measures: Eating (>= 1 instance per day) fruit, vegetables, sweets, and sugary soft drinks; eating at a fast food restaurant (>= 1 d/wk); and skipping breakfast (>= 1 d/wk).
Results: Television viewing was inversely related to intake of fruit (adjusted odds ratio, 0.92; 95% CI, 0.88-0.96) and vegetables (0.95; 0.91-1.00) and positively related to intake of candy (1.18; 1.14-1.23) and fast food (1.14; 1.09-1.19) and skipping breakfast (1.06; 1.02-1.10) after adjustment for socioeconomic factors, computer use, and physical activity. Television snacking was related to increased intake of fruit (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10), candy (1.20; 1.16-1.24), soda (1.15; 1.11-1.18), and fast food (1.09; 1.06-1.13), independent of television viewing. The relationships of television viewing with fruit and vegetable intake and with skipping breakfast were essentially unchanged after adjustment for television snacking; the relationships with intake of candy, soda, and fast food were moderately attenuated. Age and race/ethnicity modified relationships of television viewing with soda and fast food intake and with skipping breakfast.
Conclusion: Television viewing was associated with a cluster of unhealthy eating behaviors in US adolescents after adjustment for socioeconomic and behavioral covariates. Arch Pediatr Adolesc Med. 2012; 166(5): 465-472
C1 [Lipsky, Leah M.; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Ste 7B13, Bethesda, MD 20852 USA.
EM lipskylm@mail.nih.gov
OI Lipsky, Leah/0000-0003-2645-4388
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HHSN2672008000009C]; Maternal and Child Health Bureau of
the Health Resources and Services Administration
FX This research was funded by grant HHSN2672008000009C from the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development and the Maternal and Child Health
Bureau of the Health Resources and Services Administration.
NR 68
TC 26
Z9 27
U1 7
U2 40
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD MAY
PY 2012
VL 166
IS 5
SI SI
BP 465
EP 472
PG 8
WC Pediatrics
SC Pediatrics
GA 937PB
UT WOS:000303669300011
PM 22566548
ER
PT J
AU Scott, I
Webster, BR
Li, JH
Sack, MN
AF Scott, Iain
Webster, Bradley R.
Li, Jian H.
Sack, Michael N.
TI Identification of a molecular component of the mitochondrial
acetyltransferase programme: a novel role for GCN5L1
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1);
mitochonclrial metabolism; protein acetylation; sirtuin 3 (SIRT3)
ID FATTY-ACID OXIDATION; SIRT3; DEACETYLATION; PROTEIN; ACETYLATION;
RESTRICTION; SIRTUINS; BIOLOGY; ENZYME
AB SIRT3 (sirtuin 3) modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondria] protein acetylation is controlled by a counter-regulatory program has remained elusive. In the present study we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1 [GCN5 (general control of amino acid synthesis 5)-like 1; also known as Bloc l s1] counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology with a prokaryotic acetyltransferase. Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics. The results of the present study identify GCN5L1 as a critical prokaryote-derived component of the mitochondria] acetyltransferase programme.
C1 [Scott, Iain; Webster, Bradley R.; Li, Jian H.; Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
RI Li, Jianhua/B-7671-2011
OI Li, Jianhua/0000-0002-5744-3182
FU Division of Intramural Research of the NHLBI (National Heart, Lung and
Blood Institute), NIH (National Institutes of Health)
FX This work was supported by the Division of Intramural Research of the
NHLBI (National Heart, Lung and Blood Institute), NIH (National
Institutes of Health).
NR 23
TC 69
Z9 74
U1 0
U2 9
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD MAY 1
PY 2012
VL 443
BP 655
EP 661
DI 10.1042/BJ20120118
PN 3
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 941DP
UT WOS:000303944200007
PM 22309213
ER
PT J
AU Freidlin, B
Korn, EL
AF Freidlin, B.
Korn, E. L.
TI Assessing causal relationships between treatments and clinical outcomes:
always read the fine print
SO BONE MARROW TRANSPLANTATION
LA English
DT Review
DE randomized clinical trials; observational studies; causal inference;
competing risks; non-randomized comparisons
ID HIGH-DOSE CHEMOTHERAPY; RENAL-CELL CARCINOMA; PHASE-III TRIAL;
METASTATIC COLORECTAL-CANCER; CORONARY-HEART-DISEASE; INTRACRANIAL
ARTERIAL BYPASS; VITAMIN-E CONSUMPTION; BREAST-CANCER; LUNG-CANCER;
ARTHROSCOPIC SURGERY
AB Changes in clinical practice should be driven by relevant and reliable evidence. Hence, adoption of a new therapy requires demonstrating that it provides (causes) benefit. Such evidence is generally obtained from intent-to-treat analyses of randomized clinical trials (RCTs). In this paper, we review other approaches to assessing the causal relationship between treatments and outcomes: (1) inference from non-randomized (observational) studies, (2) analysis of randomized studies where patients received treatments other than those to which they were randomized and (3) analysis of studies where the outcome of interest is sometimes unobservable because of a competing event (competing risks). We conclude that for the practice-changing demonstration of a favorable benefit-to-risk ratio, the gold standard is the intent-to-treat analysis of RCTs. At the same time, we illustrate how careful application of special statistical methods for assessment of treatment-outcome causation can be instrumental in complementing existing randomized evidence and guiding design of future research. Bone Marrow Transplantation (2012) 47, 626-632; doi:10.1038/bmt.2011.119; published online 30 May 2011
C1 [Freidlin, B.; Korn, E. L.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, EPN 8122,Room 8122,6130 Execut Plaza, Bethesda, MD 20892 USA.
EM freidlinb@ctep.nci.nih.gov
NR 70
TC 2
Z9 2
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAY
PY 2012
VL 47
IS 5
BP 626
EP 632
DI 10.1038/bmt.2011.119
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 940WJ
UT WOS:000303923500003
PM 21625225
ER
PT J
AU Williams, KM
Ostrow, LW
Loeb, DM
Chung, T
Cohn, RD
Corse, AM
Mammen, AL
Chen, AR
AF Williams, K. M.
Ostrow, L. W.
Loeb, D. M.
Chung, T.
Cohn, R. D.
Corse, A. M.
Mammen, A. L.
Chen, A. R.
TI Immunohistochemistry of affected tissue may guide cGVHD treatment
decisions
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE cGVHD; rituximab; CD20; myositits
ID VERSUS-HOST-DISEASE; POLYMYOSITIS; MUSCLE; RITUXIMAB
AB Chronic graft-vs-host disease (cGVHD) myositis is a rare complication of hematopoietic SCT, for which the pathogenesis and optimal therapy are unclear. We performed immunohistochemistry on muscle biopsies from pediatric cGVHD myositis and typical cases of autoimmune dermatomyositis and polymyositis. The immunostaining pattern of cGVHD myositis was distinct from that of typical cases of autoimmunity. There was a high proportion of CD20+ and CD68+ cells, and the best therapeutic response was achieved with rituximab (anti-CD20). These results suggest that cGVHD myositis may be mediated by different leukocytes than similar autoimmune diseases and that treatment may be optimized by targeting the specific cellular infiltrates identified in affected tissue. Bone Marrow Transplantation (2012) 47, 731-733; doi:10.1038/bmt.2011.164; published online 19 September 2011
C1 [Williams, K. M.] NCI, Dept Pediat Hematol Oncol, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Ostrow, L. W.; Loeb, D. M.; Chung, T.; Cohn, R. D.; Corse, A. M.; Mammen, A. L.; Chen, A. R.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
RP Williams, KM (reprint author), NCI, Dept Pediat Hematol Oncol, Expt Transplantat & Immunol Branch, NIH, Bldg 10 CRC,Room 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM williaki@mail.nih.gov
FU NCI NIH HHS [P30 CA006973]
NR 11
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAY
PY 2012
VL 47
IS 5
BP 731
EP 733
DI 10.1038/bmt.2011.164
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 940WJ
UT WOS:000303923500018
PM 21927032
ER
PT J
AU Tan, HY
Chen, AG
Kolachana, B
Apud, JA
Mattay, VS
Callicott, JH
Chen, Q
Weinberger, DR
AF Tan, Hao Yang
Chen, Anthony G.
Kolachana, Bhaskar
Apud, Jose A.
Mattay, Venkata S.
Callicott, Joseph H.
Chen, Qiang
Weinberger, Daniel R.
TI Effective connectivity of AKT1-mediated dopaminergic working memory
networks and pharmacogenetics of anti-dopaminergic treatment
SO BRAIN
LA English
DT Article
DE antipsychotics; functional MRI; prefrontal cortex; schizophrenia;
striatum
ID DORSOLATERAL PREFRONTAL CORTEX; CATECHOL-O-METHYLTRANSFERASE;
MONOZYGOTIC TWINS DISCORDANT; NEUROPSYCHOLOGICAL DYSFUNCTION; COGNITIVE
IMPAIRMENTS; STRIATAL DOPAMINE; GENETIC-VARIATION; BASAL GANGLIA; COMT
GENOTYPE; HUMAN BRAIN
AB Working memory is a limited capacity system that integrates and manipulates information across brief periods of time, engaging a network of prefrontal, parietal and subcortical brain regions. Genetic control of these heritable brain processes have been suggested by functional genetic variations influencing dopamine signalling, which affect prefrontal activity during complex working memory tasks. However, less is known about genetic control over component working memory cortical-subcortical networks in humans, and the pharmacogenetic implications of dopamine-related genes on cognition in patients receiving anti-dopaminergic drugs. Here, we examined predictions from basic models of dopaminergic signalling in cortical and corticalsubcortical circuitries implicated in dissociable working memory maintenance and manipulation processes. We also examined pharmacogenetic effects on cognition in the context of anti-dopaminergic drug therapy. Using dynamic causal models of functional magnetic resonance imaging in normal subjects (n = 46), we identified differentiated effects of functional polymorphisms in COMT, DRD2 and AKT1 genes on prefrontal-parietal and prefrontal-striatal circuits engaged during maintenance and manipulation, respectively. Cortical synaptic dopamine monitored by the COMT Val158Met polymorphism influenced prefrontal control of both parietal processing in working memory maintenance and striatal processing in working memory manipulation. DRD2 and AKT1 polymorphisms implicated in DRD2 signalling influenced only the prefrontal-striatal network associated with manipulation. In the context of anti-psychotic drugs, the DRD2 and AKT1 polymorphisms altered dose-response effects of anti-psychotic drugs on cognition in schizophrenia (n = 111). Thus, we suggest that genetic modulation of DRD2-AKT1-related prefrontal-subcortical circuits could at least in part influence cognitive dysfunction in psychosis and its treatment.
C1 [Tan, Hao Yang; Chen, Anthony G.; Kolachana, Bhaskar; Apud, Jose A.; Mattay, Venkata S.; Callicott, Joseph H.; Chen, Qiang; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Chen, Qiang; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
RP Tan, HY (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs, Bethesda, MD 20892 USA.
EM haoyangtan@gmail.com; drweinberger@libd.org
RI Callicott, Joseph/C-9102-2009
OI Callicott, Joseph/0000-0003-1298-3334
FU National Institute of Mental Health
FX This work was funded by the National Institute of Mental Health
Intramural Research Program.
NR 56
TC 28
Z9 28
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD MAY
PY 2012
VL 135
BP 1436
EP 1445
DI 10.1093/brain/aws068
PN 5
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 937JE
UT WOS:000303654000010
PM 22525159
ER
PT J
AU Thomas, C
Kveraga, K
Huberle, E
Karnath, HO
Bar, M
AF Thomas, Cibu
Kveraga, Kestutis
Huberle, Elisabeth
Karnath, Hans-Otto
Bar, Moshe
TI Enabling global processing in simultanagnosia by psychophysical biasing
of visual pathways
SO BRAIN
LA English
DT Article
DE brain circuits; cerebral ischaemia; visual system; dorsal stream;
neurological disorders
ID SPATIAL-FREQUENCY CHANNELS; LATERAL GENICULATE-NUCLEUS; MACAQUE STRIATE
CORTEX; TOP-DOWN FACILITATION; FUNCTIONAL-ANATOMY; PARVOCELLULAR
CONTRIBUTIONS; DORSAL SIMULTANAGNOSIA; GANGLION-CELLS; EYE-MOVEMENTS;
PERCEPTION
AB A fundamental aspect of visual cognition is our disposition to see the 'forest before the trees'. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the 'forest' but not the 'trees' (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventral visual pathway, the primary recognition pathway, is intact in these patients. Here, we enabled global processing in patients with simultanagnosia using a psychophysical technique, which allowed us to bias stimuli such that they are processed predominantly by the intact ventral visual pathway. Our findings reveal that the impairment in global processing that characterizes simultanagnosia stems from a disruption in the processing of low-spatial frequencies through the dorsal pathway. These findings advance our understanding of the relationship between visuospatial attention and perception and reveal the neural mechanism mediating the disposition to see the 'forest before the trees'.
C1 [Thomas, Cibu; Kveraga, Kestutis; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Thomas, Cibu; Kveraga, Kestutis; Bar, Moshe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Huberle, Elisabeth; Karnath, Hans-Otto] Univ Tubingen, Hertie Inst Clin Brain Res, Ctr Neurol, Div Neuropsychol, D-72074 Tubingen, Germany.
[Huberle, Elisabeth] Cty Hosp Lucerne, Dept Neurol, CH-6000 Luzern, Switzerland.
[Karnath, Hans-Otto] Georgia Inst Technol, Ctr Adv Brain Imaging, Atlanta, GA 30332 USA.
[Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel.
RP Thomas, C (reprint author), NIH, 10 Ctr Dr,MSC 1240,Bldg 10,Room 3N228, Bethesda, MD 20892 USA.
EM cibu.thomas@nih.gov
FU Bundesministerium fur Bildung und Forschung (BMBF-Verbund) [01GW0654];
National Institutes of Health [R01EY019477]
FX Bundesministerium fur Bildung und Forschung (BMBF-Verbund Grant Number
01GW0654 to H-O.K.) and by the National Institutes of Health (Grant
Number R01EY019477 to M.B.).
NR 54
TC 12
Z9 12
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD MAY
PY 2012
VL 135
BP 1578
EP 1585
DI 10.1093/brain/aws066
PN 5
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 937JE
UT WOS:000303654000022
PM 22418740
ER
PT J
AU Saslow, D
Solomon, D
Lawson, HW
Killackey, M
Kulasingam, SL
Cain, J
Garcia, FAR
Moriarty, AT
Waxman, AG
Wilbur, DC
Wentzensen, N
Downs, LS
Spitzer, M
Moscicki, AB
Franco, EL
Stoler, MH
Schiffman, M
Castle, PE
Myers, ER
Comm, AAACCG
AF Saslow, Debbie
Solomon, Diane
Lawson, Herschel W.
Killackey, Maureen
Kulasingam, Shalini L.
Cain, Joanna
Garcia, Francisco A. R.
Moriarty, Ann T.
Waxman, Alan G.
Wilbur, David C.
Wentzensen, Nicolas
Downs, Levi S., Jr.
Spitzer, Mark
Moscicki, Anna-Barbara
Franco, Eduardo L.
Stoler, Mark H.
Schiffman, Mark
Castle, Philip E.
Myers, Evan R.
Comm, Acs-Asccp-Ascp Cervical Canc Guideline
TI American Cancer Society, American Society for Colposcopy and Cervical
Pathology, and American Society for Clinical Pathology screening
guidelines for the prevention and early detection of cervical cancer
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Review
ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL
SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL
INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY;
LONG-TERM RISK; WOMEN 30 YEARS; COST-EFFECTIVENESS
AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012. (C) 2012 American Cancer Society.
C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30322 USA.
[Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, Reg Network, New York, NY 10021 USA.
[Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Cain, Joanna] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA.
[Garcia, Francisco A. R.] Univ Arizona, Ctr Excellence Womens Hlth, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
[Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA.
[Waxman, Alan G.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
[Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Masonic Canc Ctr, Dept Obstet Gynecol & Womens Hlth,Div Gynecol Onc, Minneapolis, MN 55455 USA.
[Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
[Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA.
[Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Castle, Philip E.] Amer Soc, Clin Pathol Inst, Washington, DC USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Comm, Acs-Asccp-Ascp Cervical Canc Guideline] Steering Comm, Data Grp, Working Grp 1 2 3A 3B 4 5 6, Valdosta, GA USA.
[Saslow, Debbie; Castle, Philip E.; Comm, Acs-Asccp-Ascp Cervical Canc Guideline] Writing Comm, New York, NY USA.
[Cain, Joanna] Working Grp 2, Stanford, CA USA.
[Waxman, Alan G.] Working Grp 3A, Menlo Pk, CA USA.
[Garcia, Francisco A. R.; Moriarty, Ann T.] Working Grp 6, Atlanta, GA USA.
RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA.
EM debbie.saslow@cancer.org
RI Colgan, Terence/J-2339-2016;
OI Franco, Eduardo/0000-0002-4409-8084
FU Qiagen; Roche; Gen-Probe, Inc; BD; Abbott Laboratories; Roche Molecular
Systems; Merck, Inc; GlaxoSmithKline (GSK), Inc.; National Institute of
Allergy and Infectious Diseases
FX The following reported no financial relationships or potential conflicts
of interest to disclose: D. Saslow, E. Partridge, B. Holladay, W.
Kinney, H. Lawson, K. Noller, K. Poole, R. Smith, P. Fontaine, A.
Herzig, M. Killackey, S. Kulasingam, D. McCoy, W. Brewster, J. Cain, D.
Chelmow, V. King, R. Pretorius, B. Winkler, I. Eltoum, J. Kim, N.
Wentzensen, L. Downs, S. Greening, H. Haefner, L. Zephyrin, M.
Chevarie-Davis, D. Ekwueme, T. Colgan, M. Henry, S. Massad, K. Simon. P.
Castle receives payment for service on the Data Monitoring and Safety
Board for Merck Sharp & Dohme and has received free or discounted human
papillomavirus tests for research from Qiagen and Roche. C. Cohen serves
as a speaker for Merck, Inc, and receives honoraria. M. Edelson's spouse
is employed by and receives a salary from Merck and Company. F. Garcia
is employed by the University of Arizona, which holds contracts for the
performance of research with Roche Pharmaceutical/Roche Molecular;
Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton,
Dickson and Company (BD); and MediSpectra/LUMA. He also serves on the
Speakers' Bureau for Qiagen and receives honoraria. J. Cuzick serves on
advisory boards and as an ad hoc consultant for Qiagen; Roche;
Gen-Probe, Inc; BD; and Abbott Laboratories, with research funds
provided to his institution from Qiagen; Roche; Gen-Probe, Inc; BD; and
Abbott Laboratories. P. Gravitt has acted as a member of the Women's
Health Advisory Board for Qiagen Corporation and has received research
funding from Roche Molecular Systems and Merck, Inc within the last 5
years. E. Myers received research support for investigations for
Gen-Probe, Inc, and from GlaxoSmithKline (GSK), Inc. He served as a
speaker for and received honoraria from Gen-Probe, Inc, and has served
as a consultant for and received honoraria from Gen-Probe, Inc; Merck
and Company; and GSK. M. Schiffman holds a research agreement to serve
as a medical monitor in the National Cancer Institute (NCI) vaccine
trial through GSK; he also receives research support from Qiagen for
careHPV research in Nigeria. D. Solomon serves as a medical monitor for
the NCI's Costa Rica HPV Vaccine Trial; the trial receives vaccine from
GSK. M. Stoler received fees for serving as a consultant to Merck
Research Laboratories; Roche; Ventana Medical Systems, Inc; BD; Hologic;
MTM Laboratories; and Gen-Probe, Inc. D. Mody conducted lectures and
workshops for the College of American Pathologists, American Society for
Clinical Pathology, and the American Society of Cytopathology (ASC), for
which she received honoraria and/or travel expenses. G. Birdsong's
employer receives funding for contracted research performed by him for
BD Diagnostics. C. Wheeler is an employee of University of New Mexico,
which is contracted by GSK for its vaccine trials and receives
equipment/reagents from Roche Molecular Systems, Inc, for human
papillomavirus genotyping. D. Wilbur serves on the scientific advisory
board for Corista, LLC. T. Darragh received ThinPrep supplies for
research from Hologic. She also serves on an advisory board for
OncoHealth Corporation and has received stock options as payment and
serves on the advisory board of Arbor Vita Corporation. E. Mayeaux
serves on the speakers' advisory board for both Merck, Inc, and
PharmaDerm and receives honoraria from both companies for his service.
M. Spitzer serves as a speaker for both Merck, Inc, and Qiagen and
receives honoraria. K.; Ault received clinical research grants from the
National Institute of Allergy and Infectious Diseases; Gen-Probe, Inc;
Merck, Inc; and Roche and served as a site principal investigator for
the research. All grants were provided to his employer, Emory
University. E. Franco received honorarium as a Study Steering Committee
member for GSK; he also serves on the advisory boards of Merck, Inc;
Roche; and Gen-Probe, Inc, from which he receives honoraria and has
acted as an ad hoc consultant for Merck, Inc; Roche; Gen-Probe, Inc; and
Qiagen, for which honoraria were paid to compensate for time away and
work performed. M. Gold received honorarium for serving as a speaker and
consultant for Hologic. W. Huh serves as a consultant to Roche; Qiagen;
Merck, Inc; and Inovio Pharmaceuticals, Inc and receives honoraria from
all 4 companies. A-B. Moscicki received honorarium for serving as a
consultant to an advisory board for Merck, Inc. M. Einstein has advised
or participated in educational speaking activities, but does not receive
an honorarium from any companies. His employer, Montefiore Medical
Center, has received payment for his time spent on activities for Merck,
Inc; GSK; Roche; Bristol-Myers Squibb; Hologic; Advaxis, Inc; Aura
Biosciences, Inc; Inovio Pharmaceuticals, Inc; Photocure ASA;
NeoDiagnostix, Inc; and PDS Biotechnology Corporation. Montefiore has
received grant funding for research related to the costs of those Merck,
GSK, Roche, Advaxis, and Hologic clinical trials for which Dr. Einstein
served as the Montefiore principal investigator. A. Moriarty received
honorarium as a speaker for ASC. R. Guido has acted as the local
principal investigator for a multicenter study (contracted research) for
IKONOsys. A. Waxman receives honoraria and expenses for teaching related
to the subject matter in this article from nonprofit professional
organizations and governmental agencies and contractors. He is on the
executive committee of the board of directors of the American Society
for Colposcopy and Cervical Pathology; he lectures for them and
codirects some of their courses and receives honoraria and expenses for
these functions. He also lectures and directs courses for the American
College/Congress of Obstetricians and Gynecologists on subjects related
to this article and receives honoraria from them. Both organizations are
nonprofit professional organizations. He has also received honoraria and
expenses from the State of Alaska Department of Health and Social
Services and several Alaska Native corporations (Southcentral
Foundation, SouthEast Alaska Regional Health Corporation, Arctic Slope
Regional Corporation, and Yukon-Kuskokwim Health Corporation) and the
Breast Cancer Detection Center of Alaska for lecturing on material
related to this article. He also received honoraria from the Center for
Health Training, a contractor to Title X agencies for lecturing for the
Texas Department of State Health Services. He also received a $200
honorarium from Quadrant HealthCom, Inc for writing an article related
to cervical cancer screening for the journal OBG Management.
NR 156
TC 357
Z9 378
U1 14
U2 54
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD MAY-JUN
PY 2012
VL 62
IS 3
BP 147
EP 172
DI 10.3322/caac.21139
PG 26
WC Oncology
SC Oncology
GA 937NO
UT WOS:000303665400003
PM 22422631
ER
PT J
AU Partridge, AH
Elmore, JG
Saslow, D
McCaskill-Stevens, W
Schnitt, SJ
AF Partridge, Ann H.
Elmore, Joann G.
Saslow, Debbie
McCaskill-Stevens, Worta
Schnitt, Stuart J.
TI Challenges in ductal carcinoma in situ risk communication and
decision-making Report From an American Cancer Society and National
Cancer Institute Workshop
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Review
ID INVASIVE BREAST-CANCER; QUALITY-OF-LIFE; THE-SCIENCE CONFERENCE;
PSYCHOLOGICAL MORBIDITY; INFORMED DECISION; RETHINKING TNM; PERCEIVED
RISK; NORTH-AMERICA; WOMEN; DIAGNOSIS
AB In September 2010, the American Cancer Society and National Cancer Institute convened a conference to review current issues in ductal carcinoma in situ (DCIS) risk communication and decision-making and to identify directions for future research. Specific topics included patient and health care provider knowledge and attitudes about DCIS and its treatment, how to explain DCIS to patients given the heterogeneity of the disease, consideration of nomenclature changes, and the usefulness of decision tools/aids. This report describes the proceedings of the workshop in the context of the current literature and discusses future directions. Evidence suggests that there is a lack of clarity about the implications and risks of a diagnosis of DCIS among patients, providers, and researchers. Research is needed to understand better the biology and mechanisms of the progression of DCIS to invasive breast cancer and the factors that predict those subtypes of DCIS that do not progress, as well as efforts to improve the communication and informed decision-making surrounding DCIS. CA Cancer J Clin 2012. (C) 2012 American Cancer Society.
C1 [Partridge, Ann H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med, Boston, MA 02215 USA.
[Elmore, Joann G.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA.
[Saslow, Debbie] Amer Canc Soc, Atlanta, GA 30329 USA.
[McCaskill-Stevens, Worta] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Schnitt, Stuart J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
RP Partridge, AH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med, 450 Brookline Ave, Boston, MA 02215 USA.
EM ann_partridge@dfci.harvard.edu
FU NCATS NIH HHS [UL1 TR000423]
NR 63
TC 15
Z9 17
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD MAY-JUN
PY 2012
VL 62
IS 3
BP 203
EP 210
DI 10.3322/caac.21140
PG 8
WC Oncology
SC Oncology
GA 937NO
UT WOS:000303665400005
PM 22488610
ER
PT J
AU Klionsky, DJ
Hurley, JH
AF Klionsky, Daniel J.
Hurley, James H.
TI Self-eating with your fingers
SO CELL RESEARCH
LA English
DT Editorial Material
ID MEMBRANE CURVATURE; CRYSTAL-STRUCTURE; BECLIN 1; AUTOPHAGY; DOMAIN;
BINDING; PHOSPHORYLATION; MACROAUTOPHAGY; PROTEINS; ATG14L
AB BECN1 plays a central role in determining cell fate, acting as a balance point in the decision to undergo autophagy or apoptosis. Three distinct structural domains allow BECN1 to interact with several other proteins. Recent crystallographic data provide insight into the nature of the coiled-coil and evolutionarily conserved domains.
C1 [Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Klionsky, Daniel J.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
[Hurley, James H.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Klionsky, DJ (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
EM klionsky@umich.edu; hurley@helix.nih.gov
FU NIH, NIDDK; NIH [GM53396]
FX R Stanley is thanked for discussions. Research in the Hurley lab is
supported by the Intramural Program of the NIH, NIDDK. DJK is supported
by NIH grant GM53396.
NR 20
TC 2
Z9 2
U1 1
U2 11
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 MAY
PY 2012
VL 22
IS 5
BP 783
EP 785
DI 10.1038/cr.2012.39
PG 3
WC Cell Biology
SC Cell Biology
GA 936SY
UT WOS:000303611500001
PM 22410794
ER
PT J
AU O'Connell, ML
Birkenkamp, KE
Kleiner, DE
Folio, LR
Holland, SM
Olivier, KN
AF O'Connell, Meghan L.
Birkenkamp, Kate E.
Kleiner, David E.
Folio, Les R.
Holland, Steven M.
Olivier, Kenneth N.
TI Lung Manifestations in an Autopsy-Based Series of Pulmonary or
Disseminated Nontuberculous Mycobacterial Disease
SO CHEST
LA English
DT Article
ID AVIUM-INTRACELLULARE; CYSTIC-FIBROSIS; INFECTION; COMPLEX; PREVALENCE;
FEATURES
AB Background: Comparisons of lung manifestations in primary pulmonary vs disseminated nontuberculous myeobacterial disease have not been well described. The clinical, histopathologic, and radiologic disease manifestations of primary pulmonary or disseminated nontuberculous mycobacterial disease were compared in an autopsy series.
Methods: Medical and microbiologic records, autopsy reports, histopathologic slides of the lungs, and chest CT scans were reviewed on patients at the National Institutes of Health with nontuberculous mycobacterial disease who died between 1996 and 2010.
Results: The 11 patients with primary pulmonary nontuberculous mycobacterial disease were predominantly female (n = 9), with symptom onset at median 50 (range 35, 71) years and time from onset until death of 12 (3, 34) years. Bronchiectasis with cavity formation and necrotizing bronchocentric granulomatous inflammation predominated but extrapulmonary infection was absent. The five patients with disseminated disease and systemic immune defects were all men with age at onset of 2 (0.33, 33) years and time from onset of disease until death of 9 (1, 31) years. Miliary nodules and/or consolidation with poorly formed granulomatous inflammation were noted in the three disseminated patients with mycobacterial lung involvement. Significant extrapulmonary infection was noted in all five with a relative paucity of lung findings.
Conclusions: Nontuberculous mycobacteria can cause progressive, fatal disease. Primary pulmonary disease is bronchocentric and lacks extrathoracic infection consistent with impaired airway surface defenses. In contrast, fatal disseminated infections involving the lung have hematogenous spread, extensive extrathoracic disease, and a distinct pulmonary histopathology consistent with systemic immune dysfunction. CHEST 2012; 141(5):1203-1209
C1 [Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Folio, Les R.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Olivier, KN (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 10,Room 11N234, Bethesda, MD 20892 USA.
EM olivierk@niaid.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute; National Institutes of Health Clinical Center
FX This research was supported by the Intramural Research Programs of the
National Institute of Allergy and Infectious Diseases, the National
Cancer Institute, and the National Institutes of Health Clinical Center.
NR 25
TC 15
Z9 15
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 MAY
PY 2012
VL 141
IS 5
BP 1203
EP 1209
DI 10.1378/chest.11-0425
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 940PO
UT WOS:000303905700017
PM 22194586
ER
PT J
AU Remaley, AT
AF Remaley, Alan T.
TI A 54-Year-Old Diabetic Man with Low Serum Cholesterol Commentary
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Remaley, AT (reprint author), NIH, Dept Lab Med, Bldg 10,Rm 2C-433, Bethesda, MD 20892 USA.
EM aremaley1@cc.nih.gov
NR 2
TC 0
Z9 0
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 MAY
PY 2012
VL 58
IS 5
BP 830
EP 830
DI 10.1373/clinchem.2012.182147
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 937YZ
UT WOS:000303701400010
PM 22544858
ER
PT J
AU Molitoris, BA
Okusa, MD
Palevsky, PM
Kimmel, PL
Star, RA
AF Molitoris, Bruce A.
Okusa, Mark D.
Palevsky, Paul M.
Kimmel, Paul L.
Star, Robert A.
TI Designing Clinical Trials in Acute Kidney Injury
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID ACUTE-RENAL-FAILURE; MORTALITY
C1 [Kimmel, Paul L.; Star, Robert A.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
[Molitoris, Bruce A.] Indiana Univ, Dept Med, Indianapolis, IN USA.
[Molitoris, Bruce A.] Roudebush VA Med Ctr, Indianapolis, IN USA.
[Okusa, Mark D.] Univ Virginia Hlth Syst, Div Nephrol, Charlottesville, VA USA.
[Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
RP Kimmel, PL (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM KimmelP@extra.niddk.nih.gov
OI Palevsky, Paul/0000-0002-7334-5400
NR 10
TC 7
Z9 7
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAY
PY 2012
VL 7
IS 5
BP 842
EP 843
DI 10.2215/CJN.12801211
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 937AZ
UT WOS:000303632700021
PM 22442185
ER
PT J
AU Palevsky, PM
Molitoris, BA
Okusa, MD
Levin, A
Waikar, SS
Wald, R
Chertow, GM
Murray, PT
Parikh, CR
Shaw, AD
Go, AS
Faubel, SG
Kellum, JA
Chinchilli, VM
Liu, KD
Cheung, AK
Weisbord, SD
Chawla, LS
Kaufman, JS
Devarajan, P
Toto, RM
Hsu, CY
Greene, T
Mehta, RL
Stokes, JB
Thompson, AM
Thompson, BT
Westenfelder, CS
Tumlin, JA
Warnock, DG
Shah, SV
Xie, YN
Duggan, EG
Kimmel, PL
Star, RA
AF Palevsky, Paul M.
Molitoris, Bruce A.
Okusa, Mark D.
Levin, Adeera
Waikar, Sushrut S.
Wald, Ron
Chertow, Glenn M.
Murray, Patrick T.
Parikh, Chirag R.
Shaw, Andrew D.
Go, Alan S.
Faubel, Sarah G.
Kellum, John A.
Chinchilli, Vernon M.
Liu, Kathleen D.
Cheung, Alfred K.
Weisbord, Steven D.
Chawla, Lakhmir S.
Kaufman, James S.
Devarajan, Prasad
Toto, Robert M.
Hsu, Chi-yuan
Greene, Tom
Mehta, Ravindra L.
Stokes, John B.
Thompson, Aliza M.
Thompson, B. Taylor
Westenfelder, Christof S.
Tumlin, James A.
Warnock, David G.
Shah, Sudhir V.
Xie, Yining
Duggan, Emily G.
Kimmel, Paul L.
Star, Robert A.
TI Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK
Workshop on Trial Methodology
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; ACUTE-RENAL-FAILURE; CARDIAC-SURGERY;
CONSENSUS CONFERENCE; SEVERE SEPSIS; OUTCOMES; NETWORK; MORTALITY;
VETERANS; SURVIVAL
AB Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis. Clin J Am Soc Nephrol 7: 844-850, 2012. doi: 10.2215/CJN.12791211
C1 [Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Kimmel, PL (reprint author), NIDDK, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM KimmelP@extra.niddk.nih.gov
OI Murray, Patrick/0000-0001-8516-1839
NR 41
TC 38
Z9 38
U1 0
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAY
PY 2012
VL 7
IS 5
BP 844
EP 850
DI 10.2215/CJN.12791211
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 937AZ
UT WOS:000303632700022
PM 22442182
ER
PT J
AU Okusa, MD
Molitoris, BA
Palevsky, PM
Chinchilli, VM
Liu, KD
Cheung, AK
Weisbord, SD
Faubel, S
Kellum, JA
Wald, R
Chertow, GM
Levin, A
Waikar, SS
Murray, PT
Parikh, CR
Shaw, AD
Go, AS
Chavvla, LS
Kaufman, JS
Devarajan, P
Toto, RM
Hsu, CY
Greene, TH
Mehta, RL
Stokes, JB
Thompson, AM
Thompson, BT
Westenfelder, CS
Tumlin, JA
Warnock, DG
Shah, SV
Xie, YN
Duggan, EG
Kimmel, PL
Star, RA
AF Okusa, Mark D.
Molitoris, Bruce A.
Palevsky, Paul M.
Chinchilli, Vernon M.
Liu, Kathleen D.
Cheung, Alfred K.
Weisbord, Steven D.
Faubel, Sarah
Kellum, John A.
Wald, Ron
Chertow, Glenn M.
Levin, Adeera
Waikar, Sushrut S.
Murray, Patrick T.
Parikh, Chirag R.
Shaw, Andrew D.
Go, Alan S.
Chavvla, Lakhmir S.
Kaufman, James S.
Devarajan, Prasad
Toto, Robert M.
Hsu, Chi-yuan
Greene, Tom H.
Mehta, Ravindra L.
Stokes, John B.
Thompson, Aliza M.
Thompson, B. Taylor
Westenfelder, Christof S.
Tumlin, James A.
Warnock, David G.
Shah, Sudhir V.
Xie, Yining
Duggan, Emily G.
Kimmel, Paul L.
Star, Robert A.
TI Design of Clinical Trials in Acute Kidney Injury: A Report from an NIDDK
Workshop-Prevention Trials
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; CORONARY-ANGIOGRAPHY;
SODIUM-BICARBONATE; RANDOMIZED-TRIAL; OUTCOMES; INTERVENTION; SALINE
AB AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI. Clin J Ant Soc Nephrol 7: 851-855,2012. doi: 10.2215/CJN.12811211
C1 [Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Kimmel, PL (reprint author), NIDDK, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM KimmelP@extra.niddk.nih.gov
OI Murray, Patrick/0000-0001-8516-1839
NR 20
TC 22
Z9 22
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAY
PY 2012
VL 7
IS 5
BP 851
EP 855
DI 10.2215/CJN.12811211
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 937AZ
UT WOS:000303632700023
PM 22442188
ER
PT J
AU Molitoris, BA
Okusa, MD
Palevsky, PM
Chawla, LS
Kaufman, JS
Devarajan, P
Toto, RM
Hsu, CY
Greene, TH
Faubel, SG
Kellum, JA
Wald, R
Chertow, GM
Levin, A
Waikar, SS
Murray, PT
Parikh, CR
Shaw, AD
Go, AS
Chinchilli, VM
Liu, KD
Cheung, AK
Weisbord, SD
Mehta, RL
Stokes, JB
Thompson, AM
Thompson, BT
Westenfelder, CS
Turnin, JA
Warnock, DG
Shah, SV
Xie, YN
Duggan, EG
Kimmel, PL
Star, RA
AF Molitoris, Bruce A.
Okusa, Mark D.
Palevsky, Paul M.
Chawla, Lakhmir S.
Kaufman, James S.
Devarajan, Prasad
Toto, Robert M.
Hsu, Chi-yuan
Greene, Tom H.
Faubel, Sarah G.
Kellum, John A.
Wald, Ron
Chertow, Glenn M.
Levin, Adeera
Waikar, Sushrut S.
Murray, Patrick T.
Parikh, Chirag R.
Shaw, Andrew D.
Go, Alan S.
Chinchilli, Vernon M.
Liu, Kathleen D.
Cheung, Alfred K.
Weisbord, Steven D.
Mehta, Ravindra L.
Stokes, John B.
Thompson, Aliza M.
Thompson, B. Taylor
Westenfelder, Christof S.
Turnin, James A.
Warnock, David G.
Shah, Sudhir V.
Xie, Yining
Duggan, Emily G.
Kimmel, Paul L.
Star, Robert A.
TI Design of Clinical Trials in AKI: A Report from an NIDDK Workshop.
Trials of Patients with Sepsis and in Selected Hospital Settings
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; ACUTE TUBULAR-NECROSIS;
CARDIAC-SURGERY; OUTCOMES; DISEASE; MULTICENTER; MORTALITY; DIAGNOSIS;
SURVIVAL
AB AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients. Clin J Am Soc Nephrol 7: 856-860, 2012. doi: 10.2215/CJN.12821211
C1 [Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Kimmel, PL (reprint author), NIDDK, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM KimmelP@extra.niddk.nih.gov
OI Murray, Patrick/0000-0001-8516-1839
NR 27
TC 16
Z9 16
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAY
PY 2012
VL 7
IS 5
BP 856
EP 860
DI 10.2215/CJN.12821211
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 937AZ
UT WOS:000303632700024
PM 22442184
ER
PT J
AU Dorman, JS
Valdez, R
Liu, TB
Wang, C
Rubinstein, WS
O'Neill, SM
Acheson, LS
Ruffin, MT
Khoury, MJ
AF Dorman, Janice S.
Valdez, Rodolfo
Liu, Tiebin
Wang, Catharine
Rubinstein, Wendy S.
O'Neill, Suzanne M.
Acheson, Louise S.
Ruffin, Mack T.
Khoury, Muin J.
TI Health beliefs among individuals at increased familial risk for type 2
diabetes: Implications for prevention
SO DIABETES RESEARCH AND CLINICAL PRACTICE
LA English
DT Article
DE Family history; Health beliefs; Diabetes; Coronary heart disease; Stroke
ID LIFE-STYLE INTERVENTION; CORONARY-HEART-DISEASE; SCREENING TOOL;
CAROTID-ARTERY; IMPACT TRIAL; HISTORY; MELLITUS; PERCEPTIONS;
POPULATION; STROKE
AB Aim: To evaluate perceived risk, control, worry, and severity about diabetes, coronary heart disease (CHD) and stroke among individuals at increased familial risk of diabetes.
Methods: Data analyses were based on the Family Healthware (TM) Impact Trial. Baseline health beliefs were compared across three groups: (1) no family history of diabetes, CHD or stroke (n = 836), (2) family history of diabetes alone (n = 267), and (3) family history of diabetes and CHD and/or stroke (n = 978).
Results: After adjusting for age, gender, race, education and BMI, scores for perceived risk for diabetes (p < 0.0001), CHD (p < 0.0001) and stroke (p < 0.0001) were lowest in Group 1 and highest in Group 3. Similar results were observed about worry for diabetes (p < 0.0001), CHD (p < 0.0001) and stroke (p < 0.0001). Perceptions of control or severity for diabetes, CHD or stroke did not vary across the three groups.
Conclusions: Among individuals at increased familial risk for diabetes, having family members affected with CHD and/or stroke significantly influenced perceived risk and worry. Tailored lifestyle interventions for this group that assess health beliefs and emphasize approaches for preventing diabetes, as well as its vascular complications, may be an effective strategy for reducing the global burden of these serious but related chronic disorders. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Dorman, Janice S.] Univ Pittsburgh, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15261 USA.
[Valdez, Rodolfo; Liu, Tiebin; Khoury, Muin J.] Ctr Dis Control, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Wang, Catharine] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA.
[Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Dept Med, Div Genet, Evanston, IL USA.
[Rubinstein, Wendy S.] Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA.
[Rubinstein, Wendy S.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[O'Neill, Suzanne M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Acheson, Louise S.] Case Western Reserve Univ, Dept Family Med, Div Res, Cleveland, OH 44106 USA.
[Acheson, Louise S.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Acheson, Louise S.] Case Comprehens Canc Ctr, Cleveland, OH USA.
[Ruffin, Mack T.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA.
RP Dorman, JS (reprint author), Univ Pittsburgh, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15261 USA.
EM jsd@pitt.edu
OI Ruffin, Mack/0000-0001-8336-478X; Wang, Catharine/0000-0001-8584-2781
FU Centers for Disease Control; Association for Prevention Teaching and
Research [ENH-U50/CCU300860 TS-1216]; American Association of Medical
Colleges [UM-U36/CCU319276 MM-0789, CWR-U36/CCU319276 MM0630]; National
Cancer Institute [K07 CA086958, NCT00164658]
FX Sources of support: The Family Healthware (TM) Impact Trial (FHITr) was
supported through cooperative agreements between the Centers for Disease
Control and the Association for Prevention Teaching and Research
(ENH-U50/CCU300860 TS-1216) and the American Association of Medical
Colleges (Grants UM-U36/CCU319276 MM-0789 and CWR-U36/CCU319276 MM0630).
Drs. Acheson (K07 CA086958) and Wang (K07 CA131103) also received salary
support from the National Cancer Institute. Trial Registration:
NCT00164658 'Evaluating Tools for Health Promotion and Disease
Prevention'.
NR 49
TC 10
Z9 11
U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-8227
J9 DIABETES RES CLIN PR
JI Diabetes Res. Clin. Pract.
PD MAY
PY 2012
VL 96
IS 2
BP 156
EP 162
DI 10.1016/j.diabres.2011.12.017
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 937OO
UT WOS:000303668000020
PM 22257420
ER
PT J
AU Dmitriev, AA
Kashuba, VI
Haraldson, K
Senchenko, VN
Pavlova, TV
Kudryavtseva, AV
Anedchenko, EA
Krasnov, GS
Pronina, IV
Loginov, VI
Kondratieva, TT
Kazubskaya, TP
Braga, EA
Yenamandra, SP
Ignatjev, I
Ernberg, I
Klein, G
Lerman, MI
Zabarovsky, ER
AF Dmitriev, Alexey A.
Kashuba, Vladimir I.
Haraldson, Klas
Senchenko, Vera N.
Pavlova, Tatiana V.
Kudryavtseva, Anna V.
Anedchenko, Ekaterina A.
Krasnov, George S.
Pronina, Irina V.
Loginov, Vitalij I.
Kondratieva, Tatiana T.
Kazubskaya, Tatiana P.
Braga, Eleonora A.
Yenamandra, Surya P.
Ignatjev, Ilya
Ernberg, Ingemar
Klein, George
Lerman, Michael I.
Zabarovsky, Eugene R.
TI Genetic and epigenetic analysis of non-small cell lung cancer with
NotI-microarrays
SO EPIGENETICS
LA English
DT Article
DE epigenetics; lung cancer; biomarkers; tumor-suppressor gene;
NotI-microarrays; methylation; RT-qPCR; methylation specific microarrays
ID TUMOR-SUPPRESSOR GENE; HUMAN-CHROMOSOME 3; HOMOZYGOUS DELETION REGION;
REAL-TIME PCR; HUMAN GENOME; PROMOTER HYPERMETHYLATION; EPITHELIAL
MALIGNANCIES; DNA METHYLATION; SHORT ARM; 3P21.3
AB This study aimed to clarify genetic and epigenetic alterations that occur during lung carcinogenesis and to design perspective sets of newly identified biomarkers. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI clones associated with genes for hybridization with 40 paired normal/tumor DNA samples of primary lung tumors: 28 squamous cell carcinomas (SCC) and 12 adenocarcinomas (ADC). The NotI-microarray data were confirmed by qPCR and bisulfite sequencing analyses. Forty-four genes showed methylation and/or deletions in more than 15% of non-small cell lung cancer (NSCLC) samples. In general, SCC samples were more frequently methylated/deleted than ADC. Moreover, the SCC alterations were observed already at stage I of tumor development, whereas in ADC many genes showed tumor progression specific methylation/deletions. Among genes frequently methylated/deleted in NSCLC, only a few were already known tumor suppressor genes: RBSP3 (CTDSPL), VHL and THRB. The RPL32, LOC285205, FGD5 and other genes were previously not shown to be involved in lung carcinogenesis. Ten methylated genes, i.e., IQSEC1, RBSP3, ITGA9, FOXP1, LRRN1, GNAI2, VHL, FGD5, ALDH1L1 and BCL6 were tested for expression by qPCR and were found downregulated in the majority of cases. Three genes (RBSP3, FBLN2 and ITGA9) demonstrated strong cell growth inhibition activity. A comprehensive statistical analysis suggested the set of 19 gene markers, ANKRD28, BHLHE40, CGGBP1, RBSP3, EPHB1, FGD5, FOXP1, GORASP1/TTC21, IQSEC1, ITGA9, LOC285375, LRRC3B, LRRN1, MITF, NKIRAS1/RPL15, TRH, UBE2E2, VHL, WNT7A, to allow early detection, tumor progression, metastases and to discriminate between SCC and ADC with sensitivity and specificity of 80-100%.
C1 [Dmitriev, Alexey A.; Kashuba, Vladimir I.; Haraldson, Klas; Pavlova, Tatiana V.; Yenamandra, Surya P.; Ignatjev, Ilya; Ernberg, Ingemar; Klein, George; Zabarovsky, Eugene R.] Karolinska Inst, Dept Microbiol, Stockholm, Sweden.
[Dmitriev, Alexey A.; Senchenko, Vera N.; Pavlova, Tatiana V.; Kudryavtseva, Anna V.; Anedchenko, Ekaterina A.; Krasnov, George S.; Zabarovsky, Eugene R.] Engelhardt Inst Mol Biol, Moscow, Russia.
[Kashuba, Vladimir I.] Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine.
[Pronina, Irina V.; Loginov, Vitalij I.; Braga, Eleonora A.] Russian State Genet Ctr GosNIIgenetika, Moscow, Russia.
[Kondratieva, Tatiana T.; Kazubskaya, Tatiana P.] RAMS, Blokhin Canc Res Ctr, Moscow, Russia.
[Lerman, Michael I.] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA.
[Zabarovsky, Eugene R.] Linkoping Univ, Inst Klin & Expt Med, Linkoping, Sweden.
RP Zabarovsky, ER (reprint author), Karolinska Inst, Dept Microbiol, Stockholm, Sweden.
EM eugzab@ki.se
RI Dmitriev, Alexey/D-6109-2011; Senchenko, Vera/C-8992-2014; Kudryavtseva,
Anna/C-9032-2014; Krasnov, George/E-6529-2014; Braga,
Eleonora/P-5574-2016;
OI Dmitriev, Alexey/0000-0002-6827-9584; Senchenko,
Vera/0000-0002-3119-515X; Kudryavtseva, Anna/0000-0002-3722-8207;
Krasnov, George/0000-0002-6493-8378
FU Swedish Cancer Society; Swedish Institute; Swedish Research Council;
Karolinska Institute [02.740.11.5227, 16.552.11.7034]; Russian Ministry
of Education and Science; Russian Foundation for Basic Research
[10-04-01213-a, 11-04-00269]; UICC
FX We would like to thank Dr. Nina Oparina for helpful discussion of our
results. This work was supported by research grants from the Swedish
Cancer Society, the Swedish Institute, the Swedish Research Council and
Karolinska Institute, State Contracts 02.740.11.5227 and 16.552.11.7034
with the Russian Ministry of Education and Science, grants 10-04-01213-a
and 11-04-00269 from the Russian Foundation for Basic Research and by a
UICC International Cancer Technology Transfer Fellowship to DAA.
NR 52
TC 31
Z9 36
U1 2
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD MAY
PY 2012
VL 7
IS 5
BP 502
EP 513
DI 10.4161/epi.19801
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 935NB
UT WOS:000303524700011
PM 22491060
ER
PT J
AU Peltsverger, MY
Butler, PW
Alberobello, AT
Smith, S
Guevara, Y
Dubaz, OM
Luzon, JA
Linderman, J
Celi, FS
AF Peltsverger, Maya Y.
Butler, Peter W.
Alberobello, Anna Teresa
Smith, Sheila
Guevara, Yanina
Dubaz, Ornella M.
Luzon, Javier A.
Linderman, Joyce
Celi, Francesco S.
TI The-258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase
gene is associated with a shift in the pattern of secretion of thyroid
hormones following a TRH-induced acute rise in TSH
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID IODOTHYRONINE DEIODINASE; THR92ALA POLYMORPHISM; INSULIN-RESISTANCE;
THYROTROPIN; THYROXINE; DIO2; 3,5,3'-TRIIODOTHYRONINE; IDENTIFICATION;
5'-DEIODINASE; PARAMETERS
AB Objective: Type 2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The -258A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of -258A/G polymorphism on intrathyroidal thyroxine (T-4) to triiodothyronine (T-3) conversion and thyroid hormone (TH) secretion pattern, we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland.
Design: Retrospective analysis.
Methods: The TH secretion in response to 500 mu g i.v. TRH injection was studied in 45 healthy volunteers.
Results: Twenty-six subjects (16 females and ten males, 32.8 +/- 10.4 years) were homozygous for the ancestral (-258A/A) allele and 19 (11 females and eight males, 31.1 +/- 10.9 years) were carriers of the (-258G/x) variant. While no differences in the peak TSH and T-3 levels were observed, carriers of the -258G/x allele showed a blunted rise in free T-4 (FT4; P < 0.01). The -258G/x92Thr/Thr haplotype, compared with the other groups, had lower TSH values at 60 min (P < 0.03). No differences were observed between genotypes in baseline TH levels.
Conclusions: The -258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated FT4 secretion with a normal T3 release from the thyroid gland consistent with a shift in the reaction equilibrium toward the product. These data indicate that the -258G DIO2 polymorphism causes changes in the pattern of hormone secretion. These findings are a proof of concept that common polymorphisms in DIO2 can subtly affect the circulating levels of TH and might modulate the TH homeostasis.
C1 [Peltsverger, Maya Y.; Butler, Peter W.; Alberobello, Anna Teresa; Smith, Sheila; Guevara, Yanina; Dubaz, Ornella M.; Luzon, Javier A.; Linderman, Joyce; Celi, Francesco S.] NIDDK, Diabet Endocrinol & Obes Branch, CRC, Bethesda, MD 20892 USA.
[Peltsverger, Maya Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Branch, NIH, CRC, Bethesda, MD USA.
[Butler, Peter W.] Baystate Med Ctr, Endocrine & Diabet Div, Springfield, MA USA.
RP Celi, FS (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, CRC, Bldg 10,RM 6-3940,10 Ctr Dr,MSC 1613, Bethesda, MD 20892 USA.
EM fc93a@nih.gov
FU National Institute of Diabetes, Digestive, and Kidney Diseases
[Z01-DK047057-01, Z01-DK047057-02]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes, Digestive, and Kidney Diseases, programs
Z01-DK047057-01 and Z01-DK047057-02.
NR 26
TC 10
Z9 10
U1 0
U2 5
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD MAY
PY 2012
VL 166
IS 5
BP 839
EP 845
DI 10.1530/EJE-11-1073
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 939ZS
UT WOS:000303860400009
PM 22307573
ER
PT J
AU Chen, ZM
Janes, K
Chen, C
Doyle, T
Bryant, L
Tosh, DK
Jacobson, KA
Salvemini, D
AF Chen, Zhoumou
Janes, Kali
Chen, Collin
Doyle, Tim
Bryant, Leesa
Tosh, Dilip K.
Jacobson, Kenneth A.
Salvemini, Daniela
TI Controlling murine and rat chronic pain through A(3) adenosine receptor
activation
SO FASEB JOURNAL
LA English
DT Article
DE IB-MECA; MRS1898; paclitaxel; oxaliplatin; bortezomib
ID ISCHEMIC BRAIN-INJURY; PERIPHERAL NEUROPATHY; SYNAPTIC-TRANSMISSION;
RHEUMATOID-ARTHRITIS; INTERNATIONAL UNION; INFLAMMATORY PAIN;
CELL-LINES; CANCER; AGONISTS; TARGET
AB Clinical management of chronic neuropathic pain is limited by marginal effectiveness and unacceptable side effects of current drugs. We demonstrate A(3) adenosine receptor (A(3)AR) agonism as a new target-based therapeutic strategy. The development of mechanoallodynia in a well-characterized mouse model of neuropathic pain following chronic constriction injury of the sciatic nerve was rapidly and dose-dependently reversed by the A(3)AR agonists: IB-MECA, its 2-chlorinated analog (Cl-IB-MECA), and the structurally distinct MRS1898. These effects were naloxone insensitive and thus are not opioid receptor mediated. IB-MECA was >= 1.6-fold more efficacious than morphine and >5-fold more potent. In addition, IB-MECA was equally efficacious as gabapentin (Neurontin) or amitriptyline, but respectively >350- and >75-fold more potent. Besides its potent standalone ability to reverse established mechanoallodynia, IB-MECA significantly increased the antiallodynic effects of all 3 analgesics. Moreover, neuropathic pain development in rats caused by widely used chemotherapeutics in the taxane (paclitaxel), platinum-complex (oxaliplatin), and proteasome-inhibitor (bortezomib) classes was blocked by IB-MECA without antagonizing their antitumor effect. A(3)AR agonist effects were blocked with A(3)AR antagonist MRS1523, but not with A(1)AR (DPCPX) or A(2)AAR (SCH-442416) antagonists. Our findings provide the scientific rationale and pharmacological basis for therapeutic development of A(3)AR agonists for chronic pain.-Chen, Z., Janes, K., Chen, C., Doyle, T., Bryant, L., Tosh, D. K., Jacobson, K. A., Salvemini, D. Controlling murine and rat chronic pain through A(3) adenosine receptor activation. FASEB J. 26, 1855-1865 (2012). www.fasebj.org
C1 [Chen, Zhoumou; Janes, Kali; Chen, Collin; Doyle, Tim; Bryant, Leesa; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD USA.
RP Salvemini, D (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 S Grand Blvd, St Louis, MO 63104 USA.
EM salvemd@slu.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU U.S. National Institutes of Health (NIH) [R01 DA024074]; St. Louis
University; NIH National Institute of Diabetes and Digestive and Kidney
Diseases
FX The authors are grateful to Dr. Gary Bennett, (McGill University,
Montreal, QC, Canada) for critically reviewing our work. This work was
supported by U.S. National Institutes of Health (NIH) grant R01 DA024074
(D. S.), St. Louis University President Research Funds (D. S.), and the
NIH National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Program (K.A.J.). The authors report no conflicts of
interest.
NR 58
TC 39
Z9 39
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD MAY
PY 2012
VL 26
IS 5
BP 1855
EP 1865
DI 10.1096/fj.11-201541
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 937TD
UT WOS:000303680800014
PM 22345405
ER
PT J
AU Gilchrist, DA
Fromm, G
dos Santos, G
Pham, LN
McDaniel, IE
Burkholder, A
Fargo, DC
Adelman, K
AF Gilchrist, Daniel A.
Fromm, George
dos Santos, Gilberto
Pham, Linh N.
McDaniel, Ivy E.
Burkholder, Adam
Fargo, David C.
Adelman, Karen
TI Regulating the regulators: the pervasive effects of Pol II pausing on
stimulus-responsive gene networks
SO GENES & DEVELOPMENT
LA English
DT Article
DE gene expression; transcription elongation; polymerase pausing; gene
networks
ID RNA-POLYMERASE-II; EMBRYONIC STEM-CELLS; B FACTOR RELISH; TRANSCRIPTION
ELONGATION; DROSOPHILA-MELANOGASTER; P-TEFB; PROMOTER; ACTIVATION; NELF;
COMPLEX
AB The expression of many metazoan genes is regulated through controlled release of RNA polymerase II (Pol II) that has paused during early transcription elongation. Pausing is highly enriched at genes in stimulus-responsive pathways, where it has been proposed to poise downstream targets for rapid gene activation. However, whether this represents the major function of pausing in these pathways remains to be determined. To address this question, we analyzed pausing within several stimulus-responsive networks in Drosophila and discovered that paused Pol II is much more prevalent at genes encoding components and regulators of signal transduction cascades than at inducible downstream targets. Within immune-responsive pathways, we found that pausing maintains basal expression of critical network hubs, including the key NF-kappa B transcription factor that triggers gene activation. Accordingly, loss of pausing through knockdown of the pause-inducing factor NELF leads to broadly attenuated immune gene activation. Investigation of murine embryonic stem cells revealed that pausing is similarly widespread at genes encoding signaling components that regulate self-renewal, particularly within the MAPK/ERK pathway. We conclude that the role of pausing goes well beyond poising-inducible genes for activation and propose that the primary function of paused Pol II is to establish basal activity of signal-responsive networks.
C1 [Gilchrist, Daniel A.; Fromm, George; dos Santos, Gilberto; Pham, Linh N.; McDaniel, Ivy E.; 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.
EM adelmank@niehs.nih.gov
OI Gilchrist, Daniel/0000-0003-1668-2790
FU NIH, National Institute of Environmental Health Sciences [Z01 ES101987]
FX We thank the Adelman laboratory members for their helpful suggestions on
this manuscript, and Neal Silverman and Svenja Stoven for generously
providing expression constructs. This research was supported by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (Z01 ES101987).
NR 42
TC 52
Z9 54
U1 0
U2 14
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 MAY 1
PY 2012
VL 26
IS 9
BP 933
EP 944
DI 10.1101/gad.187781.112
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 935RW
UT WOS:000303538900007
PM 22549956
ER
PT J
AU Kim, YJ
Bao, H
Bonanno, L
Zhang, B
Serpe, M
AF Kim, Young-Jun
Bao, Hong
Bonanno, Liana
Zhang, Bing
Serpe, Mihaela
TI Drosophila Neto is essential for clustering glutamate receptors at the
neuromuscular junction
SO GENES & DEVELOPMENT
LA English
DT Article
DE glutamatergic synapses; postsynaptic density; glutamate receptor;
synapse assembly; auxiliary subunits; Drosophila; neuromuscular junction
ID PRESYNAPTIC NEUROTRANSMITTER RELEASE; KAINATE RECEPTORS; AUXILIARY
SUBUNITS; TRANSMEMBRANE PROTEIN; SYNAPTIC PLASTICITY; TERMINAL DOMAIN;
AMPA RECEPTORS; ACTIVE ZONES; LOCALIZATION; MELANOGASTER
AB Neurotransmitter receptor recruitment at postsynaptic specializations is key in synaptogenesis, since this step confers functionality to the nascent synapse. The Drosophila neuromuscular junction (NMJ) is a glutamatergic synapse, similar in composition and function to mammalian central synapses. Various mechanisms regulating the extent of postsynaptic ionotropic glutamate receptor (iGluR) clustering have been described, but none are known to be essential for the initial localization and clustering of iGluRs at postsynaptic densities (PSDs). We identified and characterized the Drosophila neto (neuropilin and tolloid-like) as an essential gene required for clustering of iGluRs at the NMJ. Neto colocalizes with the iGluRs at the PSDs in puncta juxtaposing the active zones. neto loss-of-function phenotypes parallel the loss-of-function defects described for iGluRs. The defects in neto mutants are effectively rescued by muscle-specific expression of neto transgenes. Neto clustering at the Drosophila NMJ coincides with and is dependent on iGluRs. Our studies reveal that Drosophila Neto is a novel, essential component of the iGluR complexes and is required for iGluR clustering, organization of PSDs, and synapse functionality.
C1 [Kim, Young-Jun; Bonanno, Liana; Serpe, Mihaela] NICHHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Bao, Hong; Zhang, Bing] Univ Oklahoma, Dept Zool, Norman, OK 73019 USA.
RP Serpe, M (reprint author), NICHHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM serpemih@mail.nih.gov
FU NIH; NIH/NINDS [R01NS06878]; NSF [IOS-0822236, IOS-1025556]
FX We thank Ed Giniger, Mark Mayer, Chi-Hon Lee, Alan Hinnebusch, Kevin
Cook, and Mike O'Connor for helpful discussions and suggestions. We are
grateful to Aaron DiAntonio, David Featherstone, and Nicholas Harden for
antibodies. We thank Peter Nguyen for technical assistance. This work
was supported in part by the Intramural Research Program at NIH. H.B.
and B.Z. were supported by grants from NIH/NINDS (R01NS06878) and NSF
(IOS-0822236 and IOS-1025556).
NR 74
TC 16
Z9 16
U1 0
U2 9
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 MAY 1
PY 2012
VL 26
IS 9
BP 974
EP 987
DI 10.1101/gad.185165.111
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 935RW
UT WOS:000303538900010
PM 22499592
ER
PT J
AU Cabral, WA
Barnes, AM
Adeyemo, A
Cushing, K
Chitayat, D
Porter, FD
Panny, SR
Gulamali-Majid, F
Tishkoff, SA
Rebbeck, TR
Gueye, SM
Bailey-Wilson, JE
Brody, LC
Rotimi, CN
Marini, JC
AF Cabral, Wayne A.
Barnes, Aileen M.
Adeyemo, Adebowale
Cushing, Kelly
Chitayat, David
Porter, Forbes D.
Panny, Susan R.
Gulamali-Majid, Fizza
Tishkoff, Sarah A.
Rebbeck, Timothy R.
Gueye, Serigne M.
Bailey-Wilson, Joan E.
Brody, Lawrence C.
Rotimi, Charles N.
Marini, Joan C.
TI A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4%
of African Americans causes lethal recessive osteogenesis imperfecta
SO GENETICS IN MEDICINE
LA English
DT Article
DE founder mutation; LEPRE1; osteogenesis imperfecta; West Africa
ID DISEASE; COLLAGEN; FREQUENCY; DEFICIENCY; CRTAP
AB Purpose: Deficiency of prolyl 3-hydroxylase 1, encoded by LEPRE1, causes recessive osteogenesis imperfecta (01). We previously identified a LEPRE1 mutation exclusively in African Americans and contemporary West Africans. We hypothesized that this allele originated in West Africa and was introduced to the Americas with the Atlantic slave trade. We aimed to determine the frequency of carriers for this mutation among African Americans and West Africans, and the mutation origin and age.
Methods: Genomic DNA was screened for the mutation using PCR and restriction digestion, and a custom TaqMan genomic single-nucleotide polymorphism assay. The mutation age was estimated using microsatellites and short tandem repeats spanning 4.2 Mb surrounding LEPRE1 in probands and carriers.
Results: Approximately 0.4% (95% confidence interval: 0.22-0.68%) of Mid-Atlantic African Americans carry this mutation, estimating recessive OI in 1/260,000 births in this population. In Nigeria and Ghana, 1.48% (95% confidence interval: 0.95-2.30%) of unrelated individuals are heterozygous carriers, predicting that 1/18,260 births will be affected with recessive 01, equal to the incidence of de novo dominant OI. The mutation was not detected in Africans from surrounding countries. All carriers shared a haplotype of 63-770 Kb, consistent with a single founder for this mutation. Using linkage disequilibrium analysis, the mutation was estimated to have originated between 650 and 900 years before present (1100-1350 CE).
Conclusion: We identified a West African founder mutation for recessive OI in LEPRE1. Nearly 1.5% of Ghanians and Nigerians are carriers. The estimated age of this allele is consistent with introduction to North America via the Atlantic slave trade (1501-1867 CE).
C1 [Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
[Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Cushing, Kelly; Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Chitayat, David] Mt Sinai Hosp, Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON M5G 1X5, Canada.
[Chitayat, David] Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada.
[Chitayat, David] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Porter, Forbes D.] NICHHD, Program Dev Genet & Endocrinol, NIH, Bethesda, MD 20892 USA.
[Panny, Susan R.] Maryland Dept Hlth & Mental Hyg, Off Genet & Children Special Hlth Care Needs, Baltimore, MD USA.
[Gulamali-Majid, Fizza] Maryland Dept Hlth & Mental Hyg, Labs Adm, Baltimore, MD USA.
[Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
[Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Abramson Canc Ctr, Philadelphia, PA USA.
[Gueye, Serigne M.] Hop Gen Grand Yoff, Dept Urol Androl, Dakar, Senegal.
[Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
RP Marini, JC (reprint author), NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Adeyemo,
Adebowale/0000-0002-3105-3231
FU National Institute of Child Health and Human Development; NHGRI;
[R01-GM076637-05]; [DP1-OD-006445-01]; [R01-CA085074]; [P50-CA105641]
FX The authors thank the members of the Ostrander Lab (National Human
Genome Research Institute, NHGRI) and Peter Chines (NHGRI) for
assistance with microsatellite genotyping and haplotype data analysis.
For assistance with African sample preparation, we thank William Beggs,
Amy Walker, Teo Tran, Charnita Zeigler-Johnson, and Elaine Spangler at
the University of Pennsylvania. For providing access to the Maryland
Department of Mental Health and Hygiene newborn metabolic screening
cards, we thank John M. DeBoy. We also thank David Eltis, coeditor of
the Transatlantic Slave Trade database, for critical reading of the
manuscript. This work was supported by the intramural research programs
of the National Institute of Child Health and Human Development (J.C.M,
F.D.P) and the NHGRI (C.N.R, L.C.B, J.E.B.-W.), as well as grant support
to S.A.T. (R01-GM076637-05 and DP1-OD-006445-01) and T.R.R (R01-CA085074
and P50-CA105641).
NR 40
TC 22
Z9 22
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD MAY
PY 2012
VL 14
IS 5
BP 543
EP 551
DI 10.1038/gim.2011.44
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 939BM
UT WOS:000303781800007
PM 22281939
ER
PT J
AU Logan, RA
AF Logan, Robert A.
TI Health Literacy Through The National Library Of Medicine
SO HEALTH AFFAIRS
LA English
DT Letter
C1 Natl Lib Med, Bethesda, MD 20894 USA.
RP Logan, RA (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAY
PY 2012
VL 31
IS 5
DI 10.1377/hlthaff.2012.0378
PG 1
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 940EP
UT WOS:000303873100040
PM 22566460
ER
PT J
AU Eisenhofer, G
Vocke, CD
Elkahloun, A
Huynh, TT
Prodanov, T
Lenders, JWM
Timmers, HJ
Benhammou, JN
Linehan, WM
Pacak, K
AF Eisenhofer, G.
Vocke, C. D.
Elkahloun, A.
Huynh, T. -T.
Prodanov, T.
Lenders, J. W. M.
Timmers, H. J.
Benhammou, J. N.
Linehan, W. M.
Pacak, K.
TI Genetic Screening for von Hippel-Lindau Gene Mutations in Non-syndromic
Pheochromocytoma: Low Prevalence and False-positives or Misdiagnosis
Indicate a Need for Caution
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE pheochromocytoma; paraganglioma; von Hippel-Lindau syndrome; mutation
testing; germline mutations; loss of heterozygosity
ID GERMLINE MUTATIONS; SPORADIC PHEOCHROMOCYTOMAS; PARAGANGLIOMA;
HEREDITARY; DISTINCT; DELETIONS; HYPOXIA; DISEASE
AB Genetic testing of tumor susceptibility genes is now recommended in most patients with pheochromocytoma or paraganglioma (PPGL), even in the absence of a syndromic presentation. Once a mutation is diagnosed there is rarely follow-up validation to assess the possibility of misdiagnosis. This study prospectively examined the prevalence of von Hippel-Lindau (VHL) gene mutations among 182 patients with non-syndromic PPGLs. Follow-up in positive cases included comparisons of biochemical and tumor gene expression data in 64 established VHL patients, with confirmatory genetic testing in cases with an atypical presentation. VHL mutations were detected by certified laboratory testing in 3 of the 182 patients with non-syndromic PPGLs. Two of the 3 had an unusual presentation of diffuse peritoneal metastases and substantial increases in plasma metanephrine, the metabolite of epinephrine. Tumor gene expression profiles in these 2 patients also differed markedly from those associated with established VHL syndrome. One patient was diagnosed with a partial deletion by Southern blot analysis and the other with a splice site mutation. Quantitative polymerase chain reaction, multiplex ligation-dependent probe amplification, and comparative genomic hybridization failed to confirm the partial deletion indicated by certified laboratory testing. Analysis of tumor DNA in the other patient with a splice site alteration indicated no loss of heterozygosity or second hit point mutation. In conclusion, VHL germline mutations represent a minor cause of non-syndromic PPGLs and misdiagnoses can occur. Caution should therefore be exercised in interpreting positive genetic test results as the cause of disease in patients with non-syndromic PPGLs.
C1 [Eisenhofer, G.] Univ Dresden, Inst Clin Chem & Lab Med, Div Clin Neurochem, D-01307 Dresden, Germany.
[Eisenhofer, G.] Univ Dresden, Dept Med 3, D-01307 Dresden, Germany.
[Vocke, C. D.; Benhammou, J. N.; Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Elkahloun, A.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Huynh, T. -T.; Prodanov, T.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Lenders, J. W. M.] Dept Internal Med, Nijmegen, Netherlands.
[Timmers, H. J.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
RP Eisenhofer, G (reprint author), Univ Dresden, Inst Clin Chem & Lab Med, Div Clin Neurochem, Fetscherstr 74, D-01307 Dresden, Germany.
EM Graeme.Eisenhofer@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015
FU Deutsche Forschungsgesellschaft; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Center for Cancer
Research, National Cancer Institute; National Human Genome Research
Institute, NIH
FX This work was supported by the Deutsche Forschungsgesellschaft and the
intramural programmes of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, the Center for Cancer Research,
National Cancer Institute, and the National Human Genome Research
Institute, NIH.
NR 25
TC 6
Z9 6
U1 1
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD MAY
PY 2012
VL 44
IS 5
BP 343
EP 348
DI 10.1055/s-0032-1304662
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 939AC
UT WOS:000303774500005
PM 22438210
ER
PT J
AU Timmers, HJLM
Taieb, D
Pacak, K
AF Timmers, H. J. L. M.
Taieb, D.
Pacak, K.
TI Current and Future Anatomical and Functional Imaging Approaches to
Pheochromocytoma and Paraganglioma
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Review
DE FDG PET; MIBG scintigraphy; FDOPA PET; FDA PET
ID POSITRON-EMISSION-TOMOGRAPHY; IN-111-PENTETREOTIDE SCINTIGRAPHY; NECK
PARAGANGLIOMAS; I-123 METAIODOBENZYLGUANIDINE; METASTATIC
PHEOCHROMOCYTOMA; OCTREOTIDE SCINTIGRAPHY; MIBG SCINTIGRAPHY; PET; HEAD;
LOCALIZATION
AB After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using I-123-metaiodobenzylguanidine or In-111-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[F-18]-fluorodopamine (F-18-FDA), 6-[F-18]-fluoro-L-3,4-dihydroxyphenylalanine (F-18-DOPA), and 2-[F-18]-fluoro-2-deoxy-D-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no 'gold-standard' imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.
C1 [Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Timmers, H. J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Taieb, D.] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, Marseille, France.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC 1E-3140,MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural NIH HHS [Z01 HD008735-08]
NR 45
TC 27
Z9 29
U1 0
U2 6
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD MAY
PY 2012
VL 44
IS 5
BP 367
EP 372
DI 10.1055/s-0031-1299712
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 939AC
UT WOS:000303774500009
PM 22399235
ER
PT J
AU Cowley, AW
Nadeau, JH
Baccarelli, A
Berecek, K
Fornage, M
Gibbons, GH
Harrison, DG
Liang, MY
Nathanielsz, PW
O'Connor, DT
Ordovas, J
Peng, WQ
Soares, MB
Szyf, M
Tolunay, HE
Wood, KC
Zhao, K
Galis, ZS
AF Cowley, Allen W., Jr.
Nadeau, Joseph H.
Baccarelli, Andrea
Berecek, Kathleen
Fornage, Myriam
Gibbons, Gary H.
Harrison, David G.
Liang, Mingyu
Nathanielsz, Peter W.
O'Connor, Daniel T.
Ordovas, Jose
Peng, Weiqun
Soares, Marcelo Bento
Szyf, Moshe
Tolunay, H. Eser
Wood, Katherine C.
Zhao, Keji
Galis, Zorina S.
TI Report of the National Heart, Lung, and Blood Institute Working Group on
Epigenetics and Hypertension
SO HYPERTENSION
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; DISEASE RISK; DEVELOPMENTAL
PLASTICITY; MISSING HERITABILITY; PRESSURE; SUSCEPTIBILITY; INHERITANCE;
GENE; MECHANISMS
C1 [Cowley, Allen W., Jr.] Med Coll Wisconsin, Dept Physiol, Ctr Cardiovasc, Milwaukee, WI 53226 USA.
[Nadeau, Joseph H.] Inst Syst Biol, Seattle, WA USA.
[Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Lab Environm Epigenet, Dept Environm Hlth,Exposure Epidemiol & Risk Prog, Boston, MA 02115 USA.
[Berecek, Kathleen] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham Comprehens Diabet Ctr, Birmingham, AL USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Gibbons, Gary H.] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Harrison, David G.] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Nathanielsz, Peter W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet Gynecol, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA.
[O'Connor, Daniel T.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Ordovas, Jose] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Ordovas, Jose] Ctr Nacl Invest Cardiovasc, Dept Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, Jose] IMDEA Alimentac, Madrid, Spain.
[Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Soares, Marcelo Bento] Northwestern Univ, Childrens Mem Res Ctr, Falk Brain Tumor Ctr, Chicago, IL 60611 USA.
[Szyf, Moshe] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
[Tolunay, H. Eser; Galis, Zorina S.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Wood, Katherine C.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Keji] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA.
RP Cowley, AW (reprint author), Med Coll Wisconsin, Dept Physiol, Ctr Cardiovasc, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM cowley@mcw.edu; jnadeau@systemsbiology.org
OI Baccarelli, Andrea/0000-0002-3436-0640; Nathanielsz,
Peter/0000-0001-8410-6280
FU National heart, Lung, and Blood Institute
FX The proceedings of the Epigenetics and Hypertension Working Group were
supported through funds provided by the National heart, Lung, and Blood
Institute.
NR 54
TC 47
Z9 48
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2012
VL 59
IS 5
BP 899
EP 905
DI 10.1161/HYPERTENSIONAHA.111.190116
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 938VH
UT WOS:000303760900014
PM 22431584
ER
PT J
AU Alderman, MH
Piller, LB
Ford, CE
Probstfield, JL
Oparil, S
Cushman, WC
Einhorn, PT
Franklin, SS
Papademetriou, V
Ong, ST
Eckfeldt, JH
Furberg, CD
Calhoun, DA
Davis, BR
AF Alderman, Michael H.
Piller, Linda B.
Ford, Charles E.
Probstfield, Jeffrey L.
Oparil, Suzanne
Cushman, William C.
Einhorn, Paula T.
Franklin, Stanley S.
Papademetriou, Vasilios
Ong, Stephen T.
Eckfeldt, John H.
Furberg, Curt D.
Calhoun, David A.
Davis, Barry R.
CA Antihypertensive & Lipid-Lowering
TI Clinical Significance of Incident Hypokalemia and Hyperkalemia in
Treated Hypertensive Patients in the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial
SO HYPERTENSION
LA English
DT Article
DE hypertension; hypokalemia; hyperkalemia; diuretic; calcium-channel
blocker; angiotensin-converting enzyme inhibitor
ID SERUM POTASSIUM; CARDIOVASCULAR EVENTS; BLOOD-PRESSURE; RISK; ALLHAT;
DIURETICS; INHIBITOR; DISEASE; BLOCKER; STROKE
AB Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine = 1.60, lisinopril = 3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C). (Hypertension. 2012;59:926-933.) . Online Data Supplement
C1 [Piller, Linda B.; Ford, Charles E.; Davis, Barry R.] Univ Texas Houston, Sch Publ Hlth, Coordinating Ctr Clin Trials, Houston, TX 77030 USA.
[Alderman, Michael H.] Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA.
[Probstfield, Jeffrey L.] Univ Washington, Clin Trials Serv Unit, Seattle, WA 98195 USA.
[Oparil, Suzanne; Calhoun, David A.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Einhorn, Paula T.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Franklin, Stanley S.] Univ Calif Irvine, Dept Med, Irvine, CA USA.
[Papademetriou, Vasilios] Vet Affairs Med Ctr Washington, Washington, DC USA.
[Ong, Stephen T.] Ong Med Ctr, Oxon Hill, MD USA.
[Eckfeldt, John H.] Univ Minnesota Hosp & Clin, Minneapolis, MN 55455 USA.
[Furberg, Curt D.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
RP Ford, CE (reprint author), Univ Texas Houston, Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler Dr,W-940, Houston, TX 77030 USA.
EM Charles.E.Ford@uth.tmc.edu
OI Papademetriou, Vasilios/0000-0002-2882-2757
FU National Heart, Lung, and Blood Institute [N01-HC-35130]; Pfizer, Inc.;
Sankyo; GlaxoSmithKline; Novartis; Amarin Pharmaceutical; Amylin
Pharmaceutical; Daiichi Sankyo Pharmaceutical; Forest-Pharmaceutical;
Johnson and Johnson; Luitpold; Pfizer; Roche; Sanofi Aventis; Takeda;
XOMA; Amgen; Daiichi Sankyo; Gilead; Merck; Abbott Laboratories;
Boehringer Ingelheim
FX This research was supported by contract number N01-HC-35130 from the
National Heart, Lung, and Blood Institute. The ALLHAT investigators
acknowledge contributions of study medications supplied by Pfizer, Inc
(amlodipine); AstraZeneca (atenolol and lisinopril); and Bristol-Myers
Squibb (pravastatin), as well as financial support by Pfizer, Inc.;
M.H.A. has received research grants from Sankyo. D.A.C. has consulted
for Eli Lilly and Novartis. W.C.C. has consulted for Daiichi Sankyo,
Novartis, Noven, Sanofi Aventis, Takeda, and Theravance, has received
honoraria from Bristol-Meyer Squibb, Daiichi Sankyo, Novartis, and
Sanofi-Aventis, and has received research grants from GlaxoSmithKline
and Novartis. B.R.D. has consulted for Amgen and Takeda. S.T.O. has
received honoraria from Novartis and has received research grants from
Amarin, Amylin, Daiichi Sankyo, Forest-Pharmaceuticals, GlaxoSmithKline,
Johnson and Johnson, Luitpold, Novartis, Pfizer, Roche, Sanofi Aventis,
Takeda, and XOMA. S.O. has consulted for Boehringer Ingelheim, Daiichi
Sankyo, Eli Lilly, Forest Laboratories, Forest Pharmaceuticals, NicOx,
Novartis, Omron Healthcare, Pfizer, and Schering Plough and has received
research grants from Amgen, Daiichi Sankyo, Gilead, Merck, and Takeda.
V.P. has received honoraria from Astra-Zeneca and Forest
Pharmaceuticals. J.L.P. has received research grants from Abbott
Laboratories, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi Aventis.
NR 20
TC 31
Z9 32
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2012
VL 59
IS 5
BP 926
EP +
DI 10.1161/HYPERTENSIONAHA.111.180554
PG 13
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 938VH
UT WOS:000303760900020
PM 22431578
ER
PT J
AU Shibao, C
Buchowski, MS
Chen, KY
Yu, C
Biaggioni, H
AF Shibao, Cyndya
Buchowski, Maciej S.
Chen, Kong Y.
Yu, Chang
Biaggioni, Halo
TI Chronic Sympathetic Attenuation and Energy Metabolism in Autonomic
Failure
SO HYPERTENSION
LA English
DT Article
DE autonomic failure; energy metabolism; energy expenditure
ID SPINAL-CORD-INJURY; NERVOUS-SYSTEM; ORTHOSTATIC HYPOTENSION; THERMOGENIC
RESPONSE; BLOOD-PRESSURE; VAGAL NERVE; HUMANS; EXPENDITURE;
RADIOIMMUNOASSAY; STIMULATION
AB The sympathetic nervous system regulates thermogenesis and energy homeostasis in humans. When activated it increases energy expenditure, particularly resting energy expenditure. Most human studies used acute infusion of beta-blockers as a model to eliminate sympathetic stimulation and to examine the contribution of the sympathetic nervous system to energy metabolism and balance. Clinically, however, it is also important to assess the effect of chronic sympathetic attenuation on energy metabolism. In this context, we hypothesized that resting energy expenditure is decreased in patients with autonomic failure who, by definition, have low sympathetic tone. We measured 24-hour energy expenditure using whole-room indirect calorimeter in 10 adults with chronic autonomic failure (6 women; age, 64.9 +/- 9.1 years; body mass index, 25.2 +/- 4.4 kg/m(2)) and 15 sedentary healthy controls of similar age and body composition (8 women; age, 63.1 +/- 4.0 years; body mass index, 24.4 +/- 3.9 kg/m(2)). In 4 patients, we eliminated residual sympathetic activity with the ganglionic bocker trimethaphan. We found that, after adjusting for body composition, resting energy expenditure did not differ between patients with autonomic failure and healthy controls. However, resting energy expenditure significantly decreased when residual sympathetic activity was eliminated. Our findings suggest that sympathetic tonic support of resting energy expenditure is preserved, at least in part, in pathophysiological models of chronic sympathetic attenuation. (Hypertension. 2012;59:985-990.)
C1 [Shibao, Cyndya; Biaggioni, Halo] Vanderbilt Univ, Sch Med, Div Clin Pharmacol & Auton Dysfunct Ctr, Nashville, TN 37240 USA.
[Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Div Gasteroenterol Energy Balance Lab, Nashville, TN USA.
[Yu, Chang] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN USA.
[Yu, Chang] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN USA.
[Chen, Kong Y.] NIDDK, Div Intramural Res, Natl Inst Hlth, Diabet Endocrinol & Obes Branch, Bethesda, MD USA.
RP Shibao, C (reprint author), 556 Robinson Res Bldg, Nashville, TN 37232 USA.
EM cyndya.shibao@vandebilt.edu
RI Buchowski, Maciej/A-2683-2008;
OI Buchowski, Maciej/0000-0002-0566-1743; Chen, Kong/0000-0002-0306-1904
FU American Heart Association; National Center for Research Resources,
National Institutes of Health [1UL1 RR024975]; National Institute of
Neurological Disorders and Stroke [U54 NS065736]; Office of Rare
Diseases Research; Rare Diseases Clinical Research Network [PO1
HL56693]; Vanderbilt Diabetes Research and Training Center [DK069465];
National Institutes of Health [K23 HL103976-01]; [DK020593]
FX C.S. is supported by National Institutes of Health grant K23 HL103976-01
and American Heart Association Clinical Research Program. M.S.B. was
supported in part by grant DK020593. Funding and/or programmatic support
for this project has been provided by Vanderbilt Clinical and
Translational Science Award grant 1UL1 RR024975 from the National Center
for Research Resources, National Institutes of Health, U54 NS065736 from
National Institute of Neurological Disorders and Stroke, the Office of
Rare Diseases Research, the Rare Diseases Clinical Research Network, PO1
HL56693, and Vanderbilt Diabetes Research and Training Center grant
DK069465.
NR 34
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2012
VL 59
IS 5
BP 985
EP 990
DI 10.1161/HYPERTENSIONAHA.111.190157
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 938VH
UT WOS:000303760900028
PM 22469621
ER
PT J
AU Battesti, A
Tsegaye, YM
Packer, DG
Majdalani, N
Gottesman, S
AF Battesti, A.
Tsegaye, Y. M.
Packer, D. G.
Majdalani, N.
Gottesman, S.
TI H-NS Regulation of IraD and IraM Antiadaptors for Control of RpoS
Degradation
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; OSMOTIC REGULATION; MOLECULAR ADAPTER; RNA-POLYMERASE;
SIGMA-FACTOR; PROTEIN; STPA; DNA; STABILITY; RSSB
AB RpoS, the master sigma factor during stationary phase and under a variety of stress conditions, is regulated at multiple levels, including regulated degradation. Degradation is dependent upon ClpXP and the RssB adaptor protein. H-NS, a nucleoid-associated protein, affects the regulated degradation of RpoS; in the absence of H-NS, RpoS is stable. The mechanisms involved in this regulation were not known. We have found that H-NS inhibits the expression of iraD and iraM, the genes coding for two anti-adaptor proteins that stabilize RpoS when overexpressed. The regulation by H-NS of iraM is independent from the previously demonstrated regulation by the PhoP/PhoQ two-component system. Moreover, differences in the behavior of several hats alleles are explained by a role for StpA, an H-NS-like protein, in the regulation of RpoS stability. This finding parallels recent observations for a role of StpA in regulation of RpoS stability in Salmonella.
C1 [Battesti, A.; Tsegaye, Y. M.; Packer, D. G.; Majdalani, N.; Gottesman, S.] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM susang@helix.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 37
TC 17
Z9 17
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD MAY
PY 2012
VL 194
IS 10
BP 2470
EP 2478
DI 10.1128/JB.00132-12
PG 9
WC Microbiology
SC Microbiology
GA 937WH
UT WOS:000303693400007
PM 22408168
ER
PT J
AU Gomes, MS
Hugo, FN
Hilgert, JB
Padilha, DMP
Simonsick, EM
Ferrucci, L
Reynolds, MA
AF Gomes, Maximiliano Schuenke
Hugo, Fernando Neves
Hilgert, Juliana Balbinot
Pereira Padilha, Dalva Maria
Simonsick, Eleanor Marie
Ferrucci, Luigi
Reynolds, Mark Allan
TI Validity of Self-reported History of Endodontic Treatment in the
Baltimore Longitudinal Study of Aging
SO JOURNAL OF ENDODONTICS
LA English
DT Article
DE Apical periodontitis; endodontic treatment; self-report; validity
ID CORONARY-HEART-DISEASE; ORAL-HEALTH; PERIODONTAL-DISEASE; APICAL
PERIODONTITIS; PERIAPICAL RADIOGRAPHY; CLINICAL EXAMINATION; POPULATION;
VALIDATION; QUESTIONNAIRE; RISK
AB Introduction: Self-reported history of endodontic treatment (SRHET) has been used as a simplified method to estimate the history of endodontic disease and treatment. This study aimed to quantify the validity of SRHET, as reported in the Baltimore Longitudinal Study of Aging (BLSA), as a method to identify individuals who experienced endodontic treatment (ET) and to identify individuals who present with apical periodontitis (AP). Methods: SRHET was collected through the BLSA questionnaire in 247 participants. Data on ET and AP were determined from panoramic radiographs. The total number of ET, AP, and missing teeth were recorded for each individual. The validity of SRHET was determined based on ET and AP separately. Accuracy, efficiency, sensitivity, specificity, positive and negative predictive values (+PV and -PV), and positive and negative likelihood ratios (+LR and -LR) were calculated according to standard methods. Results: After exclusions, 229 participants were available for ET analysis and 129 for AP analysis. The SRHET validity values were sensitivity (ET = 0.915, AP = 0.782), specificity (ET = 0.891, AP = 0.689), +PV (ET = 0.824, AP = 0.353), -PV (ET = 0.949, AP = 0.936), +LR (ET = 8.394, AP = 2.514), and -LR (ET = 0.095, AP = 0.316). Conclusions: SRHET was found to be a highly accurate method to predict ET but a weak predictor of the presence of AP among participants in the BLSA. (J Endod 2012;38:589-593)
C1 [Hugo, Fernando Neves; Hilgert, Juliana Balbinot; Pereira Padilha, Dalva Maria] Univ Fed Rio Grande do Sul, Sch Dent, Dept Community Dent, Porto Alegre, RS, Brazil.
[Gomes, Maximiliano Schuenke] Mil Police Rio Grande Sul, Med & Dent Ctr, Porto Alegre, RS, Brazil.
[Simonsick, Eleanor Marie; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Reynolds, Mark Allan] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA.
RP Gomes, MS (reprint author), Fed Univ Rio Grande Sul R Ramiro Barcelos, Sch Dent, BR-90035003 Porto Alegre, RS, Brazil.
EM endomax@gmail.com
RI Gomes, Maximiliano/O-1193-2015;
OI Gomes, Maximiliano/0000-0002-0394-5400; Hugo,
Fernando/0000-0003-2222-7719
FU NIH/NIA, National Institute on Aging; CAPES Foundation, Ministry of
Education of Brazil [1433/11-3]; Military Police, State Government of
Rio Grande do Sul, Brazil
FX Supported in part by the Intramural Research Program of the NIH/NIA,
National Institute on Aging; the CAPES Foundation, Ministry of Education
of Brazil (doctorate scholarship number 1433/11-3); and the Military
Police, State Government of Rio Grande do Sul, Brazil.
NR 35
TC 5
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0099-2399
J9 J ENDODONT
JI J. Endod.
PD MAY
PY 2012
VL 38
IS 5
BP 589
EP 593
DI 10.1016/j.joen.2012.02.006
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 940OY
UT WOS:000303904100005
PM 22515884
ER
PT J
AU Valencia, CA
Rhodenizer, D
Bhide, S
Chin, E
Littlejohn, MR
Keong, LM
Rutkowski, A
Bonnemann, C
Hegde, M
AF Valencia, C. Alexander
Rhodenizer, Devin
Bhide, Shruti
Chin, Ephrem
Littlejohn, Martin Robert
Keong, Lisa Mari
Rutkowski, Anne
Bonnemann, Carsten
Hegde, Madhuri
TI Assessment of Target Enrichment Platforms Using Massively Parallel
Sequencing for the Mutation Detection for Congenital Muscular Dystrophy
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID HYBRID SELECTION; GENERATION; CAPTURE; GENOME; DIAGNOSTICS; GENE
AB Sequencing individual genes by Sanger sequencing is a time-consuming and costly approach to resolve clinically heterogeneous genetic disorders. Panel testing offers the ability to efficiently and cost-effectively screen all of the genes for a particular genetic disorder. We assessed the analytical sensitivity and specificity of two different enrichment technologies, solution-based hybridization and microdroplet-based PCR target enrichment, in conjunction with next-generation sequencing (NGS), to identify mutations in 321 exons representing 12 different genes involved with congenital muscular dystrophies. Congenital muscular dystrophies present diagnostic challenges due to phenotypic variability, lack of standard access to and inherent difficulties with muscle immunohistochemical stains, and a general lack of clinician awareness. NGS results were analyzed across several parameters, including sequencing metrics and genotype concordance with Sanger sequencing. Genotyping data showed that both enrichment technologies produced suitable calls for use in clinical laboratories. However, microdroplet-based PCR target enrichment is more appropriate for a clinical laboratory, due to excellent sequence specificity and uniformity, reproducibility, high coverage of the target exons, and the ability to distinguish the active gene versus known pseudogenes. Regardless of the method, exons with highly repetitive and high GC regions are not well enriched and require Sanger sequencing for completeness. Our study demonstrates the successful application of targeted sequencing in conjunction with NGS to screen for mutations in hundreds of exons in a genetically heterogeneous human disorder. (J Mol Diagn 2012, 14: 233-246; DOI: 10.1016/j.jmoldx.2012.01.009)
C1 [Valencia, C. Alexander; Rhodenizer, Devin; Bhide, Shruti; Chin, Ephrem; Littlejohn, Martin Robert; Keong, Lisa Mari; Hegde, Madhuri] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Rutkowski, Anne] Cure CMD, Los Angeles, CA USA.
[Rutkowski, Anne] Kaiser So Calif Permanente Med Grp, Los Angeles, CA USA.
[Bonnemann, Carsten] NINDS, NIH, Bethesda, MD 20892 USA.
RP Hegde, M (reprint author), Whitehead Biomed Res Bldg,615 Michael St,Ste 301, Atlanta, GA 30322 USA.
EM mhegde@emory.edu
FU NIHRC [1NS 069541-01]; MDA [G6396330]; Public Health Service, NIH,
National Center for Research Resources [UL1 RR025008, KL2 R0025009, TL1
RR025010]
FX Supported by grants from NIHRC 1NS 069541-01 and MDA G6396330. In
addition, this research was supported in part by a Public Health Service
grant (UL1 RR025008, KL2 R0025009, or TL1 RR025010) from the Clinical
and Translational Science Award Program, NIH, National Center for
Research Resources.
NR 29
TC 28
Z9 28
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAY
PY 2012
VL 14
IS 3
BP 233
EP 246
DI 10.1016/j.jmoldx.2012.01.009
PG 14
WC Pathology
SC Pathology
GA 936UX
UT WOS:000303616600007
PM 22426012
ER
PT J
AU de Langen, AJ
Vincent, A
Velasquez, LM
van Tinteren, H
Boellaard, R
Shankar, LK
Boers, M
Smit, EF
Stroobants, S
Weber, WA
Hoekstra, OS
AF de Langen, Adrianus J.
Vincent, Andrew
Velasquez, Linda M.
van Tinteren, Harm
Boellaard, Ronald
Shankar, Lalitha K.
Boers, Maarten
Smit, Egbert F.
Stroobants, Sigrid
Weber, Wolfgang A.
Hoekstra, Otto S.
TI Repeatability of F-18-FDG Uptake Measurements in Tumors: A Metaanalysis
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE F-18-FDG; PET; repeatability; cancer
ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; ROI DEFINITION; FDG-PET;
RESPONSE ASSESSMENT; MALIGNANT-TUMORS; THERAPY RESPONSE; BREAST-CANCER;
UPTAKE VALUES; SOLID TUMORS
AB PET with the glucose analog F-18-FDG is increasingly used to monitor tumor response to therapy. To use quantitative measurements of tumor F-18-FDG uptake for assessment of tumor response, the repeatability of this quantitative metabolic imaging method needs to be established. Therefore, we determined the repeatability of different standardized uptake value (SUV) measurements using the available data. Methods: A systematic literature search was performed to identify studies addressing F-18-FDG repeatability in malignant tumors. The level of agreement between test and retest values of 2 PET uptake measures, maximum SUV (SUVmax) and mean SUV (SUVmean), was assessed with the coefficient of repeatability using generalized linear mixed-effects models. In addition, the influence of tumor volume on repeatability was assessed. Principal component transformation was used to compare the reproducibility of the 2 different uptake measures. Results: Five cohorts were identified for this metaanalysis. For SUVmax and SUVmean, datasets of 86 and 102 patients, respectively, were available. Percentage repeatability is a function of the level of uptake. SUVmean had the best repeatability characteristics; for serial PET scans, a threshold of a combination of 20% as well as 1.2 SUVmean units was most appropriate. After adjusting for uptake rate, tumor volume had minimal influence on repeatability. Conclusion: SUVmean had better repeatability performance than SUVmax. Both measures showed poor repeatability for lesions with low F-18-FDG uptake. We recommend the evaluation of biologic effects in PET by reporting a combination of minimal relative and absolute changes to account for test retest variability.
C1 [de Langen, Adrianus J.; Smit, Egbert F.] Vrije Univ Amsterdam Med Ctr, Dept Pulm Dis, NL-1007 MB Amsterdam, Netherlands.
[Vincent, Andrew; van Tinteren, Harm] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Biostat, Amsterdam, Netherlands.
[Velasquez, Linda M.] Bristol Myers Squibb Co, Princeton, NJ USA.
[Boellaard, Ronald; Hoekstra, Otto S.] Vrije Univ Amsterdam Med Ctr, Dept Nucl Med, NL-1007 MB Amsterdam, Netherlands.
[Boellaard, Ronald; Hoekstra, Otto S.] Vrije Univ Amsterdam Med Ctr, PET Res, NL-1007 MB Amsterdam, Netherlands.
[Shankar, Lalitha K.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA.
[Boers, Maarten] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.
[Stroobants, Sigrid] Univ Hosp Antwerpen, Dept Nucl Med, Antwerp, Belgium.
[Weber, Wolfgang A.] Univ Freiburg Klinikum, Nukl Med Klin, Freiburg, Germany.
RP de Langen, AJ (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Pulm Dis, POB 7057, NL-1007 MB Amsterdam, Netherlands.
EM j.delangen@vumc.nl
OI Boellaard, Ronald/0000-0002-0313-5686
NR 29
TC 67
Z9 67
U1 1
U2 10
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD MAY
PY 2012
VL 53
IS 5
BP 701
EP 708
DI 10.2967/jnumed.111.095299
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 939BU
UT WOS:000303782700011
PM 22496583
ER
PT J
AU Pavletic, AJ
Hnatiuk, O
AF Pavletic, Adriana J.
Hnatiuk, Oleh
TI Puzzling Dyspnea Caused by Respiratory Muscle Weakness
SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE
LA English
DT Article
DE ALS (Amyotrophic Lateral Sclerosis); Dyspnea; Neuromuscular Disorders;
Respiratory Muscles
AB Dyspnea is common in advanced stages of neuromuscular disorders, but it is infrequently the presenting symptom. However, dyspnea is a frequent complaint in a primary care setting but is rarely caused by a respiratory muscle weakness. Consequently, the diagnosis of respiratory muscle weakness often is delayed. First symptoms may occur when respiratory muscles are under increased load, such as when standing in the water higher than the chest, swimming, or in the supine position. We describe a patient in whom dyspnea was the first symptom of amyotrophic lateral sclerosis to remind clinicians of clinical features of respiratory muscle weakness and to help avoid the delay in diagnosis. (J Am Board Fam Med 2012;25:396-397.)
C1 [Pavletic, Adriana J.] NIMH, Off Clin Director, Bethesda, MD 20892 USA.
[Hnatiuk, Oleh] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP Pavletic, AJ (reprint author), NIMH, Off Clin Director, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM pavletia@mail.nih.gov
FU National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health.
NR 5
TC 2
Z9 2
U1 0
U2 1
PU AMER BOARD FAMILY MEDICINE
PI LEXINGTON
PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA
SN 1557-2625
J9 J AM BOARD FAM MED
JI J. Am. Board Fam. Med.
PD MAY-JUN
PY 2012
VL 25
IS 3
BP 396
EP 397
DI 10.3122/jabfm.2012.03.110220
PG 2
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 939KY
UT WOS:000303810600020
PM 22570404
ER
PT J
AU Figueroa, JD
Brinton, LA
AF Figueroa, Jonine D.
Brinton, Louise A.
TI Unraveling Genes, Hormones, and Breast Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID PREMENOPAUSAL WOMEN; SUSCEPTIBILITY LOCI; ASSOCIATION CONSORTIUM; SEX
STEROIDS; RISK; ESTROGENS; PROLACTIN; ANCESTRY
C1 [Figueroa, Jonine D.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Figueroa, JD (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Ste 550,Rm 5104,MSC 7234, Rockville, MD 20852 USA.
EM figueroaj@mail.nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU Intramural NIH HHS
NR 21
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 9
BP 641
EP 642
DI 10.1093/jnci/djs193
PG 2
WC Oncology
SC Oncology
GA 936PM
UT WOS:000303602500001
PM 22472542
ER
PT J
AU Umar, A
AF Umar, Asad
TI Is 15-LOX-1 a Tumor Suppressor?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CANCER CELLS; EXPRESSION; INFLAMMATION; GAMMA
C1 NCI, Gastrointestinal & Other Cancers Res Grp, Canc Prevent Div, Rockville, MD 20852 USA.
RP Umar, A (reprint author), NCI, Gastrointestinal & Other Cancers Res Grp, Canc Prevent Div, Execut Plaza N 2142,6130 Execut Blvd, Rockville, MD 20852 USA.
EM umara@mail.nih.gov
NR 11
TC 7
Z9 8
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 9
BP 645
EP 647
DI 10.1093/jnci/djs192
PG 3
WC Oncology
SC Oncology
GA 936PM
UT WOS:000303602500003
PM 22472307
ER
PT J
AU Timmers, HJLM
Chen, CC
Carrasquillo, JA
Whatley, M
Ling, A
Eisenhofer, G
King, KS
Rao, JU
Wesley, RA
Adams, KT
Pacak, K
AF Timmers, Henri J. L. M.
Chen, Clara C.
Carrasquillo, Jorge A.
Whatley, Millie
Ling, Alexander
Eisenhofer, Graeme
King, Kathryn S.
Rao, Jyotsna U.
Wesley, Robert A.
Adams, Karen T.
Pacak, Karel
TI Staging and Functional Characterization of Pheochromocytoma and
Paraganglioma by F-18-Fluorodeoxyglucose (F-18-FDG) Positron Emission
Tomography
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PET; MUTATIONS; LOCALIZATION; SDHB; DIAGNOSIS
AB Background Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of F-18-fluorodeoxyglucose positron emission tomography with computed tomography (F-18-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [I-123]-metaiodobenzylguanidine single photon emission CT (I-123-MIBG SPECT), CT, and magnetic resonance imaging (MRI).
Methods A total of 216 patients (106 men, 110 women, aged 45.2 +/- 14.9 years) with suspected PPGL underwent CT or MRI, F-18-FDG PET/CT, and I-123-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only.
Results Sixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of F-18-FDG was similar to that of I-123-MIBG but less than that of CT/MRI (sensitivity of F-18-FDG = 76.8%; of I-123-MIBG = 75.0%; of CT/MRI = 95.7%; F-18-FDG vs I-123-MIBG: difference = 1.8%, 95% confidence interval [CI] = 214.8% to 14.8%, P = .210; F-18-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for F-18-FDG, 91.8% for I-123-MIBG, and 90.2% for CT/MRI. F-18-FDG uptake was higher in succinate dehydrogenase complex-and von Hippel-Lindau syndrome-related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for F-18-FDG and CT/MRI than for I-123-MIBG (sensitivity of F-18-FDG = 82.5%; of I-123-MIBG = 50.0%; of CT/MRI = 74.4%; F-18-FDG vs I-123-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs I-123-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, F-18-FDG was more sensitive than CT/MRI (sensitivity of F-18-FDG = 93.7%; of CT/MRI = 76.7%; difference = 17.0%, 95% CI = 4.9% to 28.5%, P = .013).
Conclusions Compared with I-123-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by F-18-FDG PET. F-18-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL.
C1 [Timmers, Henri J. L. M.; Rao, Jyotsna U.] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Timmers, Henri J. L. M.; Rao, Jyotsna U.] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie] Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD USA.
[Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Ling, Alexander] Warren G Magnuson Clin Ctr, Dept Radiol & Imaging Sci, Bethesda, MD USA.
[Wesley, Robert A.] NIH, Biostat Serv, Bethesda, MD 20892 USA.
[Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, Nucl Med Sect, Dept Radiol, New York, NY 10021 USA.
[Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, Dept Med, Dept Clin Chem, Dresden, Germany.
[Eisenhofer, Graeme] Univ Dresden, Div Clin Neurochem, Dresden, Germany.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC 1E-3140,MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
OI Carrasquillo, Jorge/0000-0002-8513-5734
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development at the National Institutes of Health (NICHD/NIH); Pheo Para
Alliance; European Union [259735]
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development at the National Institutes of Health (NICHD/NIH) and Pheo
Para Alliance. The work leading to these results has received funding
from the European Union Seventh Framework Programme (FP7/2007-2013)
under grant agreement no. 259735.
NR 31
TC 70
Z9 73
U1 0
U2 9
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 MAY
PY 2012
VL 104
IS 9
BP 700
EP 708
DI 10.1093/jnci/djs188
PG 9
WC Oncology
SC Oncology
GA 936PM
UT WOS:000303602500011
PM 22517990
ER
PT J
AU Fojo, T
Amiri-Kordestani, L
Bates, SE
AF Fojo, Tito
Amiri-Kordestani, Laleh
Bates, Susan E.
TI Re: Potential Pitfalls of Crossover and Thoughts on Iniparib in
Triple-Negative Breast Cancer Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Fojo, Tito; Amiri-Kordestani, Laleh; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 9
BP 718
EP 718
DI 10.1093/jnci/djs166
PG 1
WC Oncology
SC Oncology
GA 936PM
UT WOS:000303602500016
ER
PT J
AU Engstrom, PF
AF Engstrom, Paul F.
TI Ten Years of Progress in Colon Cancer Therapy
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Engstrom, Paul F.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Engstrom, Paul F.] NCI, Bethesda, MD 20892 USA.
[Engstrom, Paul F.] Armed Forces Inst Pathol, Sci Advisory Board, Washington, DC 20306 USA.
RP Engstrom, PF (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
NR 1
TC 0
Z9 2
U1 0
U2 2
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD MAY
PY 2012
VL 10
IS 5
BP 574
EP 576
PG 3
WC Oncology
SC Oncology
GA 935YI
UT WOS:000303557700002
PM 22570287
ER
PT J
AU Bolduc, B
Shaughnessy, DP
Wolf, YI
Koonin, EV
Roberto, FF
Young, M
AF Bolduc, Benjamin
Shaughnessy, Daniel P.
Wolf, Yuri I.
Koonin, Eugene V.
Roberto, Francisco F.
Young, Mark
TI Identification of Novel Positive-Strand RNA Viruses by Metagenomic
Analysis of Archaea-Dominated Yellowstone Hot Springs
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROVIDES ACQUIRED-RESISTANCE; PROTEIN HOMOLOGY DETECTION; SHORT
PALINDROMIC REPEATS; STRUCTURE PREDICTION; VIRAL COMMUNITY;
IMMUNE-SYSTEMS; NATIONAL-PARK; CRISPR; EVOLUTION; DIVERSITY
AB There are no known RNA viruses that infect Archaea. Filling this gap in our knowledge of viruses will enhance our understanding of the relationships between RNA viruses from the three domains of cellular life and, in particular, could shed light on the origin of the enormous diversity of RNA viruses infecting eukaryotes. We describe here the identification of novel RNA viral genome segments from high-temperature acidic hot springs in Yellowstone National Park in the United States. These hot springs harbor low-complexity cellular communities dominated by several species of hyperthermophilic Archaea. A viral metagenomics approach was taken to assemble segments of these RNA virus genomes from viral populations isolated directly from hot spring samples. Analysis of these RNA metagenomes demonstrated unique gene content that is not generally related to known RNA viruses of Bacteria and Eukarya. However, genes for RNA-dependent RNA polymerase (RdRp), a hallmark of positive-strand RNA viruses, were identified in two contigs. One of these contigs is approximately 5,600 nucleotides in length and encodes a polyprotein that also contains a region homologous to the capsid protein of nodaviruses, tetraviruses, and birnaviruses. Phylogenetic analyses of the RdRps encoded in these contigs indicate that the putative archaeal viruses form a unique group that is distinct from the RdRps of RNA viruses of Eukarya and Bacteria. Collectively, our findings suggest the existence of novel positive-strand RNA viruses that probably replicate in hyperthermophilic archaeal hosts and are highly divergent from RNA viruses that infect eukaryotes and even more distant from known bacterial RNA viruses. These positive-strand RNA viruses might be direct ancestors of RNA viruses of eukaryotes.
C1 [Bolduc, Benjamin; Shaughnessy, Daniel P.; Young, Mark] Montana State Univ, Thermal Biol Inst, Bozeman, MT 59717 USA.
[Young, Mark] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA.
[Shaughnessy, Daniel P.; Young, Mark] Montana State Univ, Dept Plant Sci & Plant Pathol, Bozeman, MT 59717 USA.
[Bolduc, Benjamin] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA.
[Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Roberto, Francisco F.] Idaho Natl Lab, Idaho Falls, ID USA.
RP Young, M (reprint author), Montana State Univ, Thermal Biol Inst, Bozeman, MT 59717 USA.
EM myoung@montana.edu
FU National Science Foundation [DEB-0936178, EF-080220]; National
Aeronautics and Space Administration [NNA-08CN85A]; Department of Health
and Human Services (NIH, National Library of Medicine)
FX This work was supported by National Science Foundation grant numbers
DEB-0936178 and EF-080220 and National Aeronautics and Space
Administration grant number NNA-08CN85A. Y.I.W. and E.V.K. are supported
by the Department of Health and Human Services intramural program (NIH,
National Library of Medicine).
NR 75
TC 44
Z9 46
U1 1
U2 21
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5562
EP 5573
DI 10.1128/JVI.07196-11
PG 12
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100014
PM 22379100
ER
PT J
AU Heiss, BL
Maximova, OA
Thach, DC
Speicher, JM
Pletnev, AG
AF Heiss, Brian L.
Maximova, Olga A.
Thach, Dzung C.
Speicher, James M.
Pletnev, Alexander G.
TI MicroRNA Targeting of Neurotropic Flavivirus: Effective Control of Virus
Escape and Reversion to Neurovirulent Phenotype
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RNA RECOMBINATION; DENGUE TYPE-4; ENCEPHALITIS; REGION; PATHOGENICITY;
INTERFERENCE; RECOGNITION; ATTENUATION; MECHANISMS; EXPRESSION
AB Neurotropic flaviviruses can efficiently replicate in the developing and mature central nervous systems (CNS) of mice causing lethal encephalitis. Insertion of a single copy of a target for brain-expressed microRNAs (miRNAs) in the 3' noncoding region (3'NCR) of the flavivirus genome (chimeric tick-borne encephalitis virus/dengue virus) abolished virus neurovirulence in the mature mouse CNS. However, in the developing CNS of highly permissive suckling mice, the miRNA-targeted viruses can revert to a neurovirulent phenotype by accumulating deletions or mutations within the miRNA target sequence. Virus escape from miRNA-mediated suppression in the developing CNS was markedly diminished by increasing the number of miRNA target sites and by extending the distance between these sites in the virus genome. Insertion of multiple miRNA targets into the 3'NCR altered virus neuroinvasiveness, decreased neurovirulence and neuroinflammatory responses, and prevented neurodegeneration without loss of immunogenicity. Although the onset of encephalitis was delayed, a small number of suckling mice still succumbed to lethal intracerebral infection with the miRNA-targeted viruses. Sequence analysis of brain isolates from moribund mice revealed that the viruses escaped from miRNA-mediated suppression exclusively through the deletion of miRNA targets and viral genome sequence located between the two miRNA targets separated by the greatest distance. These findings offer a general strategy to control the reversion of virus to a virulent phenotype: a simultaneous miRNA targeting of the viral genome at many different functionally important regions could prevent virus escape from miRNA-based attenuation, since a deletion of the targeted genomic sequences located between the inserted miRNA binding sites would be lethal for the virus.
C1 [Heiss, Brian L.; Maximova, Olga A.; Thach, Dzung C.; Speicher, James M.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM apletnev@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases. We do not have a conflict of financial or other
interest.
NR 37
TC 26
Z9 27
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5647
EP 5659
DI 10.1128/JVI.07125-11
PG 13
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100022
PM 22419812
ER
PT J
AU Shukla, P
Nguyen, HT
Faulk, K
Mather, K
Torian, U
Engle, RE
Emerson, SU
AF Shukla, P.
Nguyen, H. T.
Faulk, K.
Mather, K.
Torian, U.
Engle, R. E.
Emerson, S. U.
TI Adaptation of a Genotype 3 Hepatitis E Virus to Efficient Growth in Cell
Culture Depends on an Inserted Human Gene Segment Acquired by
Recombination
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CIS-REACTIVE ELEMENT; HYPERVARIABLE REGION; ANIMAL RESERVOIRS; RNA
SEQUENCE; PATIENT; PROTEIN; REPLICATION; INFECTION; REVEALS; RELEASE
AB An infectious cDNA clone of a genotype 3 strain of hepatitis E virus adapted to growth in HepG2/C3A human hepatoma cells was constructed. This virus was unusual in that the hypervariable region of the adapted virus contained a 171-nucleotide insertion that encoded 58 amino acids of human S17 ribosomal protein. Analyses of virus from six serial passages indicated that genomes with this insert, although initially rare, were selected during the first passage, suggesting it conferred a significant growth advantage. RNA transcripts from this cDNA and the viruses encoded by them were infectious for cells of both human and swine origin, the major host species for this zoonotic virus. Mutagenesis studies demonstrated that the S17 insert was a major factor in cell culture adaptation. Introduction of 54 synonymous mutations into the insert had no detectable effect, thus implicating protein, rather than RNA, as the important component. Truncation of the insert by 50% decreased the levels of successful transfection by similar to 3-fold. Substitution of the S17 sequence by a different ribosomal protein sequence or by GTPase-activating protein sequence resulted in a partial enhancement of transfection levels, whereas substitution with 58 amino acids of green fluorescent protein had no effect. Therefore, both the sequence length and the amino acid composition of the insert were important. The S17 sequence did not affect transfection of human hepatoma cells when inserted into the hypervariable region of a genotype 1 strain, but this chimeric genome acquired a dramatic ability to replicate in hamster cells.
C1 [Emerson, S. U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 34
TC 58
Z9 59
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5697
EP 5707
DI 10.1128/JVI.00146-12
PG 11
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100026
PM 22398290
ER
PT J
AU Brock, LG
Karron, RA
Krempl, CD
Collins, PL
Buchholz, UJ
AF Brock, Linda G.
Karron, Ruth A.
Krempl, Christine D.
Collins, Peter L.
Buchholz, Ursula J.
TI Evaluation of Pneumonia Virus of Mice as a Possible Human Pathogen
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; HOUSE MICE; SEROLOGICAL SURVEY;
ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HEPARAN-SULFATE; GENOME SEQUENCE;
DENDRITIC CELLS; MUS-DOMESTICUS; MESSENGER-RNA
AB Pneumonia virus of mice (PVM), a relative of human respiratory syncytial virus (RSV), causes respiratory disease in mice. There is serologic evidence suggesting widespread exposure of humans to PVM. To investigate replication in primates, African green monkeys (AGM) and rhesus macaques (n = 4) were inoculated with PVM by the respiratory route. Virus was shed intermittently at low levels by a subset of animals, suggesting poor permissiveness. PVM efficiently replicated in cultured human cells and inhibited the type I interferon (IFN) response in these cells. This suggests that poor replication in nonhuman primates was not due to a general nonpermissiveness of primate cells or poor control of the IFN response. Seroprevalence in humans was examined by screening sera from 30 adults and 17 young children for PVM-neutralizing activity. Sera from a single child (6%) and 40% of adults had low neutralizing activity against PVM, which could be consistent with increasing incidence of exposure following early childhood. There was no cross-reaction of human or AGM sera between RSV and PVM and no cross-protection in the mouse model. In native Western blots, human sera reacted with RSV but not PVM proteins under conditions in which AGM immune sera reacted strongly. Serum reactivity was further evaluated by flow cytometry using unfixed Vero cells infected with PVM or RSV expressing green fluorescent protein (GFP) as a measure of viral gene expression. The reactivity of human sera against RSV-infected cells correlated with GFP expression, whereas reactivity against PVM-infected cells was low and uncorrelated with GFP expression. Thus, PVM specificity was not evident. Our results indicate that the PVM-neutralizing activity of human sera is not due to RSV- or PVM-specific antibodies but may be due to low-affinity, polyreactive natural antibodies of the IgG subclass. The absence of PVM-specific antibodies and restriction in nonhuman primates makes PVM unlikely to be a human pathogen.
C1 [Brock, Linda G.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Karron, Ruth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA.
[Krempl, Christine D.] Univ Wurzburg, Inst Virol & Immunbiol, D-8700 Wurzburg, Germany.
RP Buchholz, UJ (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ubuchholz@niaid.nih.gov
RI Krempl, Christine/O-2081-2015
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 73
TC 7
Z9 7
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5829
EP 5843
DI 10.1128/JVI.00163-12
PG 15
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100039
PM 22438539
ER
PT J
AU Wu, XL
Wang, C
O'Dell, S
Li, YX
Keele, BF
Yang, ZJ
Imamichi, H
Doria-Rose, N
Hoxie, JA
Connors, M
Shaw, GM
Wyatt, RT
Mascola, JR
AF Wu, Xueling
Wang, Charlene
O'Dell, Sijy
Li, Yuxing
Keele, Brandon F.
Yang, Zhongjia
Imamichi, Hiromi
Doria-Rose, Nicole
Hoxie, James A.
Connors, Mark
Shaw, George M.
Wyatt, Richard T.
Mascola, John R.
TI Selection Pressure on HIV-1 Envelope by Broadly Neutralizing Antibodies
to the Conserved CD4-Binding Site
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBTYPE-C INFECTION; RECOMBINANT
GLYCOPROTEIN-120 VACCINE; MULTIPLE SEQUENCE ALIGNMENT; HUMAN
MONOCLONAL-ANTIBODY; TYPE-1 INFECTION; HIGH-THROUGHPUT; EVOLUTION;
GP120; RESPONSES
AB The monoclonal antibody (MAb) VRC01 was isolated from a slowly progressing HIV-1-infected donor and was shown to neutralize diverse HIV-1 strains by binding to the conserved CD4 binding site (CD4bs) of gp120. To better understand the virologic factors associated with such antibody development, we characterized HIV-1 envelope (Env) variants from this donor and five other donors who developed broadly neutralizing antibodies. A total of 473 env sequences were obtained by single-genome amplification, and 100 representative env clones were expressed and tested for entry and neutralization sensitivity. While VRC01 neutralizes about 90% of the genetically diverse heterologous HIV-1 strains tested, only selective archival Env variants from the VRC01 donor were sensitive to VRC01 and all of the Env variants derived from the donor plasma were resistant, indicating strong antibody-based selection pressure. Despite their resistance to this broadly reactive MAb that partially mimics CD4, all Env variants required CD4 for entry. Three other CD4bs MAbs from the same donor were able to neutralize some VRC01 escape variants, suggesting that CD4bs antibodies continued to evolve in response to viral escape. We also observed a relatively high percentage of VRC01-resistant Env clones in the plasma of four of five additional broadly neutralizing donors, suggesting the presence of CD4bs-directed neutralizing antibodies in these donors. In total, these data indicate that the CD4bs-directed neutralizing antibodies exert ongoing selection pressure on the conserved CD4bs epitope of HIV-1 Env.
C1 [Wu, Xueling; Wang, Charlene; O'Dell, Sijy; Yang, Zhongjia; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Imamichi, Hiromi; Doria-Rose, Nicole; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Li, Yuxing; Wyatt, Richard T.] Scripps Res Inst, Dept Med & Microbial Sci, IAVI Ctr Neutralizing Antibodies TSRI, La Jolla, CA 92037 USA.
[Keele, Brandon F.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA.
[Hoxie, James A.; Shaw, George M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
FU Vaccine Research Center, NIAID, NIH; NIH [AI067854]; Bill & Melinda
Gates Foundation [37874]
FX Support for this work was provided by the Intramural Research Program of
the Vaccine Research Center, NIAID, NIH. G.M.S. was supported by grants
from the NIH (AI067854) and the Bill & Melinda Gates Foundation Grand
Challenges Program (37874).
NR 82
TC 45
Z9 46
U1 1
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5844
EP 5856
DI 10.1128/JVI.07139-11
PG 13
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100040
PM 22419808
ER
PT J
AU Yamamoto, T
Johnson, MJ
Price, DA
Wolinsky, DI
Almeida, JR
Petrovas, C
Nason, M
Yeh, WW
Shen, L
Roederer, M
Rao, SS
McDermott, AB
Lefebvre, F
Nabel, GJ
Haddad, EK
Letvin, NL
Douek, DC
Koup, RA
AF Yamamoto, Takuya
Johnson, Matthew J.
Price, David A.
Wolinsky, David I.
Almeida, Jorge R.
Petrovas, Constantinos
Nason, Martha
Yeh, Wendy W.
Shen, Ling
Roederer, Mario
Rao, Srinivas S.
McDermott, Adrian B.
Lefebvre, Francois
Nabel, Gary J.
Haddad, Elias K.
Letvin, Norman L.
Douek, Daniel C.
Koup, Richard A.
TI Virus Inhibition Activity of Effector Memory CD8(+) T Cells Determines
Simian Immunodeficiency Virus Load in Vaccinated Monkeys after Vaccine
Breakthrough Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CONVERGENT RECOMBINATION; IMMUNE-RESPONSES; HIV-1 INFECTION; SIV
INFECTION; RECEPTOR; VIREMIA; ESCAPE; DISEASE; USAGE
AB The goal of an effective AIDS vaccine is to generate immunity that will prevent human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress toward this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime-recombinant adenovirus serotype 5 (rAd5) boost vaccination with simian immunodeficiency virus strain mac239 (SIVmac239) Gag-Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8(+) T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8(+) T cells showed strong virus-inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8(+) T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8(+) T cells. The ability to elicit such virus-specific EM CD8(+) T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection.
C1 [Yamamoto, Takuya; Johnson, Matthew J.; Price, David A.; Wolinsky, David I.; Almeida, Jorge R.; Petrovas, Constantinos; Roederer, Mario; Rao, Srinivas S.; McDermott, Adrian B.; Nabel, Gary J.; Douek, Daniel C.; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nason, Martha] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
[Yeh, Wendy W.; Shen, Ling; Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Lefebvre, Francois; Haddad, Elias K.] VGTI FL, Port St Lucie, FL USA.
RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rkoup@mail.nih.gov
RI Yamamoto, Takuya/L-2642-2013; Price, David/C-7876-2013;
OI Yamamoto, Takuya/0000-0003-3753-1211; Price, David/0000-0001-9416-2737;
Ramos de Almeida, Jorge/0000-0002-5009-8478
FU Vaccine Research Center, NIAID, National Institutes of Health; Harvard
Medical School Center for AIDS Research [AI060354]; Bill & Melinda Gates
Foundation [OPP1032325]
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID, National Institutes of Health, Harvard
Medical School Center for AIDS Research grant AI060354, and
Collaboration for AIDS Vaccine Discovery (CAVD) grant number OPP1032325
from the Bill & Melinda Gates Foundation.
NR 33
TC 26
Z9 28
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5877
EP 5884
DI 10.1128/JVI.00315-12
PG 8
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100043
PM 22419810
ER
PT J
AU Boyer, PL
Clark, PK
Hughes, SH
AF Boyer, Paul L.
Clark, Patrick K.
Hughes, Stephen H.
TI HIV-1 and HIV-2 Reverse Transcriptases: Different Mechanisms of
Resistance to Nucleoside Reverse Transcriptase Inhibitors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL DRUG-RESISTANCE;
T-LYMPHOCYTES; DE-NOVO; MUTATIONS; EXCISION; EMERGENCE; SUBDOMAIN;
INFECTION; COMPLEX
AB As anti-HIV therapy becomes more widely available in developing nations, it is clear that drug resistance will continue to be a major problem. The related viruses HIV-1 and HIV-2 share many of the same resistance pathways to nucleoside reverse transcriptase inhibitors (NRTIs). However, clinical data suggest that while HIV-1 reverse transcriptase (RT) usually uses an ATP-dependent excision pathway to develop resistance to the nucleoside analog zidovudine (AZT), HIV-2 RT does not appear to use this pathway. We previously described data that suggested that wild-type (WT) HIV-2 RT has a much lower ability to excise AZT monophosphate (AZTMP) than does WT HIV-1 RT and suggested that this is the reason that HIV-2 RT more readily adopts an exclusion pathway against AZT triphosphate (AZTTP), while HIV-1 RT is better able to exploit the ATP-dependent pyrophosphorolysis mechanism. However, we have now done additional experiments, which show that while HIV-1 RT can adopt either an exclusion- or excision-based resistance mechanism against AZT, HIV-2 RT can use only the exclusion mechanism. All of our attempts to make HIV-2 RT excision competent did not produce an AZT-resistant RI but instead yielded RTs that were less able to polymerize than the WT. This suggests that the exclusion pathway is the only pathway available to HIV-2.
C1 [Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Clark, Patrick K.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
EM hughesst@mail.nih.gov
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; National Cancer Institute, NIH [HHSN26120080001E]
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Cancer Institute,
Center for Cancer Research, and in part with federal funds from the
National Cancer Institute, NIH, under contract HHSN26120080001E.
NR 40
TC 19
Z9 19
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5885
EP 5894
DI 10.1128/JVI.06597-11
PG 10
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100044
PM 22438533
ER
PT J
AU Howard, AR
Moss, B
AF Howard, Amanda R.
Moss, Bernard
TI Formation of Orthopoxvirus Cytoplasmic A-Type Inclusion Bodies and
Embedding of Virions Are Dynamic Processes Requiring Microtubules
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ACTIN-BASED MOTILITY; VACCINIA VIRUS A26; COWPOX VIRUS; INTRACELLULAR
MOVEMENT; MATURE VIRIONS; MAJOR PROTEIN; MATRIX; GENE; TRANSLATION;
PARTICLES
AB In cells infected with some orthopoxviruses, numerous mature virions (MVs) become embedded within large, cytoplasmic A-type inclusions (ATIs) that can protect infectivity after cell lysis. ATIs are composed of an abundant viral protein called ATIp, which is truncated in orthopoxviruses such as vaccinia virus (VACV) that do not form ATIs. To study ATI formation and occlusion of MVs within ATIs, we used recombinant VACVs that express the cowpox full-length ATIp or we transfected plasmids encoding ATIp into cells infected with VACV, enabling ATI formation. ATI enlargement and MV embedment required continued protein synthesis and an intact microtubular network. For live imaging of ATIs and MVs, plasmids expressing mCherry fluorescent protein fused to ATIp were transfected into cells infected with VACV expressing the viral core protein A4 fused to yellow fluorescent protein. ATIs appeared as dynamic, mobile bodies that enlarged by multiple coalescence events, which could be prevented by disrupting microtubules. Coalescence of ATIs was confirmed in cells infected with cowpox virus. MVs were predominantly at the periphery of Ails early in infection. We determined that coalescence contributed to the distribution of MVs within Ails and that microtubule-disrupting drugs abrogated coalescence-mediated MV embedment. In addition, MVs were shown to move from viral factories at speeds consistent with microtubular transport to the peripheries of ATIs, whereas disruption of microtubules prevented such trafficking. The data indicate an important role for microtubules in the coalescence of ATIs into larger structures, transport of MVs to Ails, and embedment of MVs within the ATI matrix.
C1 [Howard, Amanda R.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, NIAID, NIH
FX The work was supported by the Division of Intramural Research, NIAID,
NIH.
NR 33
TC 6
Z9 6
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5905
EP 5914
DI 10.1128/JVI.06997-11
PG 10
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100046
PM 22438543
ER
PT J
AU Xiao, S
Paldurai, A
Nayak, B
Samuel, A
Bharoto, EE
Prajitno, TY
Collins, PL
Samal, SK
AF Xiao, Sa
Paldurai, Anandan
Nayak, Baibaswata
Samuel, Arthur
Bharoto, Eny E.
Prajitno, Teguh Y.
Collins, Peter L.
Samal, Siba K.
TI Complete Genome Sequences of Newcastle Disease Virus Strains Circulating
in Chicken Populations of Indonesia
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FUSION PROTEIN; VIRULENCE
AB Eight highly virulent Newcastle disease virus (NDV) strains were isolated from vaccinated commercial chickens in Indonesia during outbreaks in 2009 and 2010. The complete genome sequences of two NDV strains and the sequences of the surface protein genes (F and HN) of six other strains were determined. Phylogenetic analysis classified them into two new subgroups of genotype VII in the class II cluster that were genetically distinct from vaccine strains. This is the first report of complete genome sequences of NDV strains isolated from chickens in Indonesia.
C1 [Xiao, Sa; Paldurai, Anandan; Nayak, Baibaswata; Samuel, Arthur; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Bharoto, Eny E.] Vaksindo Satwa Nusantara, Jakarta, Indonesia.
[Prajitno, Teguh Y.] Japfa Comfeed Indonesia, Jakarta, Indonesia.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU NIAID [N01A060009]; NIAID, NIH
FX This work was supported by NIAID contract N01A060009 (85% support) and
the NIAID, NIH, Intramural Research Program (15% support).
NR 8
TC 21
Z9 24
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5969
EP 5970
DI 10.1128/JVI.00546-12
PG 2
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100061
PM 22532534
ER
PT J
AU Wentzensen, N
AF Wentzensen, Nicolas
TI Screening for anal cancer: endpoints needed
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID CERVICAL-CANCER; INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS;
PREVENTION
C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
NR 8
TC 10
Z9 11
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAY
PY 2012
VL 13
IS 5
BP 438
EP 440
DI 10.1016/S1470-2045(12)70101-8
PG 4
WC Oncology
SC Oncology
GA 935HC
UT WOS:000303508700024
PM 22445258
ER
PT J
AU Madan, RA
Mohebtash, M
Arlen, PM
Vergati, M
Rauckhorst, M
Steinberg, SM
Tsang, KY
Poole, DJ
Parnes, HL
Wright, JJ
Dahut, WL
Schlom, J
Gulley, JL
AF Madan, Ravi A.
Mohebtash, Mahsa
Arlen, Philip M.
Vergati, Matteo
Rauckhorst, Myrna
Steinberg, Seth M.
Tsang, Kwong Y.
Poole, Diane J.
Parnes, Howard L.
Wright, John J.
Dahut, William L.
Schlom, Jeffrey
Gulley, James L.
TI Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in
metastatic castration-resistant prostate cancer: a phase 1
dose-escalation trial
SO LANCET ONCOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; IMMUNOTHERAPY; MELANOMA; SURVIVAL; CTLA-4;
AUTOIMMUNITY; PROGRESSION; CARCINOMA; BLOCKADE; SAFETY
AB Background Therapeutic cancer vaccines have shown activity in metastatic castration-resistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic T-lymphocyte-associated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigen-presenting cells. We aimed to assess the safety and tolerability of ipilimumab in combination with a poxviral-based vaccine targeting prostate-specific antigen (PSA) and containing transgenes for T-cell co-stimulatory molecule expression, including CD80.
Methods We did a phase 1 dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipilimumab in combination with a fixed dose of the PSA-Tricom vaccine. Patients with mCRPC received 2x10(8) plaque-forming units of recombinant vaccinia PSA-Tricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1x10(9) plaque-forming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. This study is registered with ClinicalTrials.gov, number NCT00113984.
Findings We completed enrolment with 30 patients (24 of whom had not been previously treated with chemotherapy) and we did not identify any dose-limiting toxic effects. Grade 1 and 2 vaccination-site reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immune-related adverse events. Grade 3 or 4 immune-related adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immune-related adverse events (two patients), and grade 4 neutropenia (one patient). Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapy-naive, 14 (58%) had PSA declines from baseline, of which six were greater than 50%.
Interpretation The use of a vaccine targeting PSA that also enhances co-stimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC.
C1 [Madan, Ravi A.; Mohebtash, Mahsa; Arlen, Philip M.; Vergati, Matteo; Rauckhorst, Myrna; Tsang, Kwong Y.; Poole, Diane J.; Schlom, Jeffrey; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Madan, Ravi A.; Arlen, Philip M.; Parnes, Howard L.; Wright, John J.; Dahut, William L.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU US National Institutes of Health; Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX US National Institutes of Health.; We acknowledge the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health, for its support of this study.
We also express appreciation to the professionals at the NIH Clinical
Center Blood Bank for their part in apheresis procedures for study
patients, and to the medical oncology fellows at the National Cancer
Institute for their attention to patient care. We thank Bonnie L Casey
and Debra Weingarten for their editorial assistance in the preparation
of this report.
NR 31
TC 148
Z9 149
U1 4
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAY
PY 2012
VL 13
IS 5
BP 501
EP 508
DI 10.1016/S1470-2045(12)70006-2
PG 8
WC Oncology
SC Oncology
GA 935HC
UT WOS:000303508700041
PM 22326924
ER
PT J
AU Galanis, E
Wu, WT
Cloughesy, T
Lamborn, K
Mann, B
Wen, PY
Reardon, DA
Wick, W
Macdonald, D
Armstrong, TS
Weller, M
Vogelbaum, M
Colman, H
Sargent, DJ
van den Bent, MJ
Gilbert, M
Chang, S
AF Galanis, Evanthia
Wu, Wenting
Cloughesy, Timothy
Lamborn, Kathleen
Mann, Bhupinder
Wen, Patrick Y.
Reardon, David A.
Wick, Wolfgang
Macdonald, David
Armstrong, Terri S.
Weller, Michael
Vogelbaum, Michael
Colman, Howard
Sargent, Daniel J.
van den Bent, Martin J.
Gilbert, Mark
Chang, Susan
TI Phase 2 trial design in neuro-oncology revisited: a report from the RANO
group
SO LANCET ONCOLOGY
LA English
DT Review
ID II CLINICAL-TRIALS; NEWLY-DIAGNOSED GLIOBLASTOMA; RANDOMIZED
DISCONTINUATION DESIGN; GLIOMAS RESPONSE ASSESSMENT; RECURRENT
GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; PROGNOSTIC-FACTORS; PLUS
TEMOZOLOMIDE; RADIATION-THERAPY; MALIGNANT GLIOMA
AB Advances in the management of gliomas, including the approval of agents such as temozolomide and bevacizumab, have created an evolving therapeutic landscape in glioma treatment, thus affecting our ability to reliably use historical controls to comparatively assess the activity of new therapies. Furthermore, the increasing availability of novel, targeted agents-which are competing for a small patient population, in view of the low incidence of primary brain tumours-draws attention to the need to improve the efficiency of phase 2 clinical testing in neuro-oncology to expeditiously transition the most promising of these drugs or combinations to potentially practice-changing phase 3 trials. In this report from the Response Assessment in Neurooncology (RANO) group, we review phase 2 trial designs that can address these challenges and capitalise on scientific and clinical advances in brain tumour treatment in neuro-oncology to accelerate and optimise the selection of drugs deserving further testing in phase 3 trials. Although there is still a small role for single-arm and non-comparative phase 2 designs, emphasis is placed on the potential role that comparative randomised phase 2 designs-such as screening designs, selection designs, discontinuation designs, and adaptive designs, including seamless phase 2/3 designs-can have. The rational incorporation of these designs, as determined by the specific clinical setting and the trial's endpoints or goals, has the potential to substantially advance new drug development in neuro-oncology.
C1 [Galanis, Evanthia] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA.
[Wu, Wenting; Sargent, Daniel J.] Mayo Clin, Dept Stat, Rochester, MN 55905 USA.
[Cloughesy, Timothy] Ronald Reagan UCLA Med Ctr, Neurooncol Program, Los Angeles, CA USA.
[Lamborn, Kathleen; Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Mann, Bhupinder] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Wen, Patrick Y.; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wick, Wolfgang] Univ Heidelberg, Dept Neurooncol, Heidelberg, Germany.
[Wick, Wolfgang] German Canc Res Ctr, D-6900 Heidelberg, Germany.
[Macdonald, David] London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada.
[Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Sch Nursing, Dept Integrated Care, Houston, TX USA.
[Armstrong, Terri S.; Gilbert, Mark] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Vogelbaum, Michael] Cleveland Clin, Dept Neurol Surg, Cleveland, OH 44106 USA.
[Colman, Howard] Univ Utah, Dept Neurosurg, Salt Lake City, UT USA.
[van den Bent, Martin J.] Erasmus Univ, Med Ctr, Dept Neurooncol, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands.
RP Galanis, E (reprint author), Mayo Clin, Dept Oncol, Rochester, MN 55905 USA.
EM galanis.evanthia@mayo.edu
FU Roche; Novartis; Amgen; AstraZeneca; Sanofi-Aventis; Genentech; Vascular
Biogenics; Esai; Exelixis; MSD; Boehinger-Ingelheim; Merck; Merck
Serono; Bayer Onyx; Myrexis; Schering
FX MJvdB has a consultant role with Roche, MSD, Siena Biotech, Antisense
Pharma, and Merck Ag; and has received honoraria from MSD and research
funding from Roche. MV has a consultant role with Merck, Bristol-Myers
Squibb, and Pharmaco-kinesis. TC has a consultant role with
Genentech/Roche, Lilly, Novartis, and Agio; and has received honoraria
from Merck. PYW has a consultant role with Novartis, Merck, and Stemline
Therapeutics; and has received honoraria from Merck and research support
from Novartis, Amgen, AstraZeneca, Sanofi-Aventis, Genentech, Vascular
Biogenics, Esai, and Exelixis. DAR has a consultant role with
Genentech/Roche, EMD Serono, and Merck/Schering; and has received
honoraria from Genentech/Roche, EMD Serono, and Merck/Schering. WWi has
a consultant role with Roche, Magforce, and MSD; and has received
honoraria from MSD and research funding from MSD and
Boehinger-Ingelheim. TSA has received honoraria from Merck and research
funding from Merck and Genentech. MW has a consultant role with Roche,
Merck, and SMD; and has received research funding from Roche and Merck
Serono. HC has a consultant role with Castle Biosciences and has
received research funding from Bayer Onyx and Myrexis. MG has a
consultant role with Genentech, Merck, and Abbott; and has received
honoraria and research funding from Merck and Genentech. SC has received
research funding from Novartis and Schering. DM has received honoraria
from Merck and Roche. EG, WWu, DJS, KL, and BM declare that they have no
conflicts of interest in relation to this manuscript.
NR 47
TC 23
Z9 23
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAY
PY 2012
VL 13
IS 5
BP E196
EP E204
PG 9
WC Oncology
SC Oncology
GA 935HC
UT WOS:000303508700016
PM 22554547
ER
PT J
AU Baskar, S
Wiestner, A
Wilson, WH
Pastan, I
Rader, C
AF Baskar, Sivasubramanian
Wiestner, Adrian
Wilson, Wyndham H.
Pastan, Ira
Rader, Christoph
TI Targeting malignant B cells with an immunotoxin against ROR1
SO MABS
LA English
DT Article
DE ROR1; immunotoxin; monoclonal antibody; chronic lymphocytic leukemia;
mantle cell lymphoma
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RECEPTOR TYROSINE KINASE; STABILIZED FV
FRAGMENTS; PSEUDOMONAS EXOTOXIN-A; RECOMBINANT IMMUNOTOXIN;
RFB4(DSFV)-PE38 BL22; HEMATOLOGIC MALIGNANCIES; MONOCLONAL-ANTIBODY;
CYTOTOXIC ACTIVITY; CLL CELLS
AB The selective cell surface expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) has made ROR1 a novel and promising target for therapeutic monoclonal antibodies (mAbs). Four mouse mAbs generated by hybridoma technology exhibited specific binding to human ROR1 (hROR1). Epitope mapping studies showed that two mAbs (2A2 and 2D11) recognized N-terminal epitopes in the extracellular region of ROR1 and the other two (1A1 and 1A7) recognized C-terminal epitopes. A ROR1-immunotoxin (BT-1) consisting of truncated Pseudomonas exotoxin A ( PE 38) and the V H and V L fragments of 2A2-IgG was made recombinantly. Both 2A2-IgG and BT-1 showed dose-dependent and selective binding to primary CLL and MCL cells and MCL cell lines. Kinetic analyses revealed 0.12-nM (2A2-IgG) to 65-nM (BT-1) avidity/affinity to hROR1, depicting bivalent and monovalent interactions, respectively. After binding to cell surface ROR1, 2A2-IgG and BT-1 were partially internalized by primary CLL cells and MCL cell lines, and BT-1 induced profound apoptosis of ROR1-expressing MCL cell lines in vitro (EC50 = 16 pM-16 nM), but did not affect ROR1-negative cell lines. Our data suggest that ROR1-immunotoxins such as BT-1 could serve as targeted therapeutic agents for ROR1-expressing B cell malignancies and other cancers.
C1 [Baskar, Sivasubramanian; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Baskar, S (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM baskars@mail.nih.gov
FU National Institutes of Health [National Cancer Institute and National
Heart, Lung and Blood Institute]
FX This work was funded by the Intramural Research Program of the National
Institutes of Health [National Cancer Institute and National Heart, Lung
and Blood Institute]. We thank Mr. Michael G. Kennedy and Dr. Jiahui
Yang for the generation of recombinant ROR1 proteins, Dr. Anders Rosen
for providing the 232-B4 cell line and Dr. William G. Telford and Ms.
Veena Kapoor for maintaining the flow cytometry core facility.
NR 51
TC 27
Z9 28
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD MAY-JUN
PY 2012
VL 4
IS 3
BP 349
EP 361
DI 10.4161/mabs.19870
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 938LT
UT WOS:000303735700007
PM 22531447
ER
PT J
AU Koay, CG
Ozarslan, E
Johnson, KM
Meyerand, ME
AF Koay, Cheng Guan
Oezarslan, Evren
Johnson, Kevin M.
Meyerand, M. Elizabeth
TI Sparse and optimal acquisition design for diffusion MRI and beyond
SO MEDICAL PHYSICS
LA English
DT Article
DE sparse design; optimal acquisition; diffusion MRI; multiple-shell
acquisition; 3D radial MRI; moderately greedy combinatorial search;
combinatorial optimization
ID FAST SPIN-ECHO; HUMAN BRAIN; WEIGHTED MRI; RESOLUTION; RECONSTRUCTION;
CONTRAST; OPTIMIZATION; ANGIOGRAPHY; FRAMEWORK; SCHEMES
AB Purpose: Diffusion magnetic resonance imaging (MRI) in combination with functional MRI promises a whole new vista for scientists to investigate noninvasively the structural and functional connectivity of the human brain-the human connectome, which had heretofore been out of reach. As with other imaging modalities, diffusion MRI data are inherently noisy and its acquisition time-consuming. Further, a faithful representation of the human connectome that can serve as a predictive model requires a robust and accurate data-analytic pipeline. The focus of this paper is on one of the key segments of this pipeline-in particular, the development of a sparse and optimal acquisition (SOA) design for diffusion MRI multiple-shell acquisition and beyond.
Methods: The authors propose a novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and a novel and effective semistochastic and moderately greedy combinatorial search strategy with simulated annealing to locate the optimum design or configuration. The goal of the optimality criteria is threefold: first, to maximize uniformity of the diffusion measurements in each shell, which is equivalent to maximal incoherence in angular measurements; second, to maximize coverage of the diffusion measurements around each radial line to achieve maximal incoherence in radial measurements for multiple-shell acquisition; and finally, to ensure maximum uniformity of diffusion measurement directions in the limiting case when all the shells are coincidental as in the case of a single-shell acquisition. The approach taken in evaluating the stability of various acquisition designs is based on the condition number and the A-optimal measure of the design matrix.
Results: Even though the number of distinct configurations for a given set of diffusion gradient directions is very large in general-e.g., in the order of 10(232) for a set of 144 diffusion gradient directions, the proposed search strategy was found to be effective in finding the optimum configuration. It was found that the square design is the most robust (i.e., with stable condition numbers and A-optimal measures under varying experimental conditions) among many other possible designs of the same sample size. Under the same performance evaluation, the square design was found to be more robust than the widely used sampling schemes similar to that of 3D radial MRI and of diffusion spectrum imaging (DSI).
Conclusions: A novel optimality criterion for sparse multiple-shell acquisition and quasimultiple-shell designs in diffusion MRI and an effective search strategy for finding the best configuration have been developed. The results are very promising, interesting, and practical for diffusion MRI acquisitions. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.3700166]
C1 [Koay, Cheng Guan; Johnson, Kevin M.; Meyerand, M. Elizabeth] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Oezarslan, Evren] NICHHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Oezarslan, Evren] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Meyerand, M. Elizabeth] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53705 USA.
RP Koay, CG (reprint author), Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53705 USA.
EM cgkoay@wisc.edu
RI Ozarslan, Evren/B-4858-2013
OI Ozarslan, Evren/0000-0003-0859-1311
FU National Institutes of Health [IRCMH090912-01]; Department of Defense in
the Center for Neuroscience and Regenerative Medicine (CNRM); Henry M.
Jackson Foundation (HJF)
FX C.G.K. dedicates this work to Pauline Toh and Eng Khoon Leong. Software
related to this work will be made available through the following URL:
http://sites.google.com/site/hispeedpackets. This work was supported in
part by the National Institutes of Health Grant No. IRCMH090912-01. E.O.
was supported by the Department of Defense in the Center for
Neuroscience and Regenerative Medicine (CNRM) and the Henry M. Jackson
Foundation (HJF).
NR 66
TC 11
Z9 11
U1 0
U2 7
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD MAY
PY 2012
VL 39
IS 5
BP 2499
EP 2511
DI 10.1118/1.3700166
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 936QE
UT WOS:000303604300020
PM 22559620
ER
PT J
AU Hewitt, SC
Li, LP
Grimm, SA
Chen, Y
Liu, LW
Li, Y
Bushel, PR
Fargo, D
Korach, KS
AF Hewitt, Sylvia C.
Li, Leping
Grimm, Sara A.
Chen, Yu
Liu, Liwen
Li, Yin
Bushel, Pierre R.
Fargo, David
Korach, Kenneth S.
TI Research Resource: Whole-Genome Estrogen Receptor alpha Binding in Mouse
Uterine Tissue Revealed by ChIP-Seq
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; GENE-EXPRESSION; PROGESTERONE-RECEPTOR; NULL
MUTATION; TARGET GENES; IN-VIVO; CELLS; EXPOSURE; UTERUS; HOXA10
AB To advance understanding of mechanisms leading to biological and transcriptional endpoints related to estrogen action in the mouse uterus, we have mapped ER alpha and RNA polymerase II (PolII) binding sites using chromatin immunoprecipitation followed by sequencing of enriched chromatin fragments. In the absence of hormone, 5184 ER alpha-binding sites were apparent in the vehicle-treated ovariectomized uterine chromatin, whereas 17,240 were seen 1 h after estradiol (E-2) treatment, indicating that some sites are occupied by unliganded ER alpha, and that ER alpha binding is increased by E-2. Approximately 15% of the uterine ER alpha-binding sites were adjacent to (<10 kb) annotated transcription start sites, and many sites are found within genes or are found more than 100 kb distal from mapped genes; however, the density (sites per base pair) of ER alpha-binding sites is significantly greater adjacent to promoters. An increase in quantity of sites but no significant positional differences were seen between vehicle and E-2-treated samples in the overall locations of ER alpha-binding sites either distal from, adjacent to, or within genes. Analysis of the PolII data revealed the presence of poised promoter-proximal PolII on some highly up-regulated genes. Additionally, corecruitment of PolII and ER alpha to some distal enhancer regions was observed. A de novo motif analysis of sequences in the ER alpha-bound chromatin confirmed that estrogen response elements were significantly enriched. Interestingly, in areas of ER alpha binding without predicted estrogen response element motifs, homeodomain transcription factor-binding motifs were significantly enriched. The integration of the ER alpha- and PolII-binding sites from our uterine sequencing of enriched chromatin fragments data with transcriptional responses revealed in our uterine microarrays has the potential to greatly enhance our understanding of mechanisms governing estrogen response in uterine and other estrogen target tissues. (Molecular Endocrinology 26: 887-898, 2012)
C1 [Hewitt, Sylvia C.; Li, Yin; Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Li, Leping; Bushel, Pierre R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Liu, Liwen] NIEHS, Biostat Branch, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Hewitt, SC (reprint author), NIEHS, Lab Reprod & Dev Toxicol, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM curtiss@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health [Z01ES70065, Z01ES101765]
FX This work was supported by National Institutes of Health Intramural
Research project numbers Z01ES70065 (to S.C.H., Y.L., and K.S.K.) and
Z01ES101765 (to L. Li).
NR 48
TC 36
Z9 37
U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2012
VL 26
IS 5
BP 887
EP 898
DI 10.1210/me.2011-1311
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 940BL
UT WOS:000303864900016
PM 22446102
ER
PT J
AU Li, M
Du, X
Villaruz, AE
Diep, BA
Wang, DC
Song, Y
Tian, YR
Hu, JH
Yu, FY
Lu, Y
Otto, M
AF Li, Min
Du, Xin
Villaruz, Amer E.
Diep, Binh An
Wang, Decheng
Song, Yan
Tian, Yueru
Hu, Jinhui
Yu, Fangyou
Lu, Yuan
Otto, Michael
TI MRSA epidemic linked to a quickly spreading colonization and virulence
determinant
SO NATURE MEDICINE
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; NASAL COLONIZATION; GENOME SEQUENCE; 2
HOSPITALS; INFECTIONS; EVOLUTION; ADHERENCE; CARRIAGE; STRAINS; EVASION
AB The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood(1). Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer(2), there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare(3,4) mobile genetic element-encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.
C1 [Villaruz, Amer E.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Li, Min; Du, Xin; Song, Yan; Tian, Yueru; Hu, Jinhui; Lu, Yuan] Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Lab Med, Shanghai 200433, Peoples R China.
[Diep, Binh An] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA.
[Wang, Decheng] Fudan Univ, Shanghai Med Coll, Inst Med Microbiol, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.
[Wang, Decheng] Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.
[Yu, Fangyou] Wenzhou Med Coll, Affiliated Hosp 1, Dept Lab Med, Wenzhou, Peoples R China.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yuanlu@hsh.stn.sh.cn; motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU China National Clinical Key Subject; National Natural Science Foundation
of China [30900026, 81171623]; Shanghai Pujiang Program [09PJ1402300];
National Institute of Allergy and Infectious Diseases, US National
Institutes of Health
FX This study was supported by a grant from the China National Clinical Key
Subject to Y.L., the National Natural Science Foundation of China
(grants 30900026 and 81171623) and the Shanghai Pujiang Program (grant
09PJ1402300) to M.L., and the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, US National
Institutes of Health (to M.O.).
NR 30
TC 98
Z9 120
U1 3
U2 41
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAY
PY 2012
VL 18
IS 5
BP 816
EP U217
DI 10.1038/nm.2692
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 938WE
UT WOS:000303763500050
PM 22522561
ER
PT J
AU Federoff, M
Jimenez-Rolando, B
Nalls, MA
Singleton, AB
AF Federoff, Monica
Jimenez-Rolando, Belen
Nalls, Michael A.
Singleton, Andrew B.
TI A large study reveals no association between APOE and Parkinson's
disease
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Parkinson's disease; Genetics; APOE
ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; DEMENTIA; ALLELE; METAANALYSIS;
POPULATION; PREVALENCE; ONSET; RISK
AB Background: Research focusing on the role of APOE in Parkinson's disease (PD) has been largely inconclusive. creating a broad discrepancy in association studies.
Objective: To elucidate the role of APOE alleles in PD risk by studying a large sample size and controlling for population substructure.
Patients and methods: In total, 3465 case and control samples were genotyped, obtained from the NINDS Neurogenetics repository.
Results: No significant differences in epsilon 4 dosages exist between PD cases and controls. The frequency of epsilon 4 carriers differed slightly between cases and controls at 24% (580/2412) and 26% (270/1053), respectively. Likewise, mean dosages of APOE 62 were not significantly different between cases and controls. APOE epsilon 2 carriers were observed at a frequency of 13.6% (329/2412) among cases and 15% (158/1053) among controls. Logistic regression models evaluating PD as possibly associated with epsilon 4 or epsilon 2 carrier status and allele dosages yielded no significant results. The mean MMSE score among all PD cases was 28.35 (SD = 2.58) and memory loss was reported in only 11.9% (105/879) of cases. Linear regression models comparing MMSE scores as predicted by epsilon 4 or epsilon 2 carrier status and allele dosages were not significant.
Conclusions: There is no association between APOE epsilon alleles and Parkinson's disease. Published by Elsevier Inc.
C1 [Federoff, Monica; Jimenez-Rolando, Belen; Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [Z01 AG000950-09]
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, Department
of Health and Human Services; project number Z01 AG000950-09. This study
used samples from the NINDS Human Genetics Resource Center DNA and Cell
Line Repository (http://ccr.coriell.org/ninds), as well as clinical
data.
NR 17
TC 26
Z9 27
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAY
PY 2012
VL 46
IS 2
BP 389
EP 392
DI 10.1016/j.nbd.2012.02.002
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 937BC
UT WOS:000303633000015
PM 22349451
ER
PT J
AU Matthews, E
Plotz, PH
Portaro, S
Parton, M
Elliott, P
Humbel, RL
Holton, JL
Keegan, BM
Hanna, MG
AF Matthews, E.
Plotz, P. H.
Portaro, S.
Parton, M.
Elliott, P.
Humbel, R. L.
Holton, J. L.
Keegan, B. M.
Hanna, M. G.
TI A case of necrotizing myopathy with proximal weakness and cardiomyopathy
SO NEUROLOGY
LA English
DT Editorial Material
ID SIGNAL RECOGNITION PARTICLE; IDIOPATHIC INFLAMMATORY MYOPATHY;
DIFFERENTIAL-DIAGNOSIS; BORRELIA-BURGDORFERI; CLINICAL-FEATURES; LYME
MYOSITIS; DERMATOMYOSITIS; POLYMYOSITIS; AUTOANTIBODIES; PATHOGENESIS
C1 [Matthews, E.; Portaro, S.; Parton, M.; Holton, J. L.; Hanna, M. G.] UCL, Inst Neurol, MRC Ctr Neuromuscular Dis, London, England.
[Plotz, P. H.] NIH, Bethesda, MD 20892 USA.
[Elliott, P.] Univ Coll London Hosp, Dept Cardiol, Heart Hosp, London, England.
[Humbel, R. L.] Immunopathol Lab, Esch Sur Alzette, Luxembourg.
[Portaro, S.] Univ Messina, AOU Policlin G Martino, Dept Neurosci Psychiat & Anesthesiol, Messina, Italy.
[Keegan, B. M.] Mayo Clin, Dept Neurol, Rochester, MN USA.
RP Hanna, MG (reprint author), UCL, Inst Neurol, MRC Ctr Neuromuscular Dis, London, England.
EM m.hanna@ucl.ac.uk
RI Hanna, Michael/B-1995-2009; Holton, Janice/F-6831-2011
OI Holton, Janice/0000-0002-3882-5249
FU Medical Research Council [G0601943]
NR 31
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY
PY 2012
VL 78
IS 19
BP 1527
EP 1532
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 939AW
UT WOS:000303776900016
PM 22565568
ER
PT J
AU Tang, BS
Lee, SM
Kim, HS
Shin, IS
Razjouyan, F
Wang, ST
Yao, ZS
Pastan, I
Dreher, MR
Paik, CH
AF Tang, Beom-Su
Lee, Sang-Myung
Kim, Hyung Sub
Shin, In Soo
Razjouyan, Faezeh
Wang, Shutao
Yao, Zhengsheng
Pastan, Ira
Dreher, Matthew R.
Paik, Chang H.
TI Combined-modality radioimmunotherapy: synergistic effect of paclitaxel
and additive effect of bevacizumab
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
ID METASTATIC BREAST-CANCER; INTERSTITIAL FLUID PRESSURE; B3
MONOCLONAL-ANTIBODY; BINDING-SITE BARRIER; REFRACTORY LOW-GRADE; SOLID
TUMORS; PHASE-I; COMPARATIVE BIODISTRIBUTION; CARCINOEMBRYONIC ANTIGEN;
BIOLOGICAL IMPEDIMENTS
AB Introduction: This study was undertaken to investigate the effect of paclitaxel and bevacizumab on the therapeutic efficacy of Y-90-labeled B3 monoclonal antibody, directed against Le(y) antigen, for the treatment of Le(y)-positive A431 tumors implanted subcutaneously in the right hind flank of nude mice.
Methods: When the tumor size reached similar to 200 mm(3), the mice received a single dose of intravenous (iv) Y-90-labeled B3 (60 mu Ci/150 mu g or 100 mu Ci/150 mu g B3), intraperitoneal paclitaxel (40 mg/kg) or iv bevacizumab (5 mg/kg) for monotherapy. To investigate the effect of combined therapies on survival, the mice were treated with two or three agents in the following combinations: Y-90-B3 on day 0 and paclitaxel on day 1; bevacizumab on -1 day and Y-90-B3 on day -1; bevacizumab on 1 day and paclitaxel on day 1; bevacizumab, Y-90-B3 and paclitaxel each at I-day intervals. The mice with no treatment were used as a control. The tumor volume at 1000 mm3 was used as a surrogate end point of survival.
Results: Compared to control animals, paclitaxel delayed tumor growth with a significantly longer median survival time (P<.001), whereas bevacizumab alone showed a less pronounced effect on a median survival time (P=.18). Y-90-B3 increased the median survival time in a dose-dependent manner (P<.05). The combined therapy of bevacizumab with paclitaxel produced a trend toward an increase of the median survival time compared to paclitaxel alone (P=.06), whereas bevacizumab combined with Y-90-B3 showed a statistically insignificant increase in the median survival time compared to Y-90-B3 alone (P=.25). The tumor sizes of all animals in these groups reached the surrogate end point of survival by day 35. In contrast, the combined therapy involving Y-90-B3 with paclitaxel showed a striking synergistic effect in shrinking tumors and prolonging the survival time (P<.001); on day 120, three of nine mice (33%) and six of six mice (100%) were alive without tumor when treated with 60 mu Ci Y-90-B3 and 100 mu Ci Y-90-B3, respectively. The addition of bevacizumab treatment 1 day before the combined therapy of 60 mu Ci Y-90-B3 with paclitaxel did not produce a statistically significant increase in survival when compared to the Y-90-B3 with paclitaxel (P>.10). Fluorescence microscopy analysis indicated that paclitaxel increased, whereas bevacizumab decreased, the accumulation and penetration of Alexa Fluor 647-B3 into tumor microenvironment compared to the control (P<.05).
Conclusion: Our findings on the paclitaxel effect support a hypothesis that the increased tumor accumulation and penetration of Y-90-B3 as well as the high radiosensitization of tumor cells by paclitaxel may be the major factors responsible for the synergistic effect of the combined therapy involving Y-90-B3 with paclitaxel. Published by Elsevier Inc.
C1 [Tang, Beom-Su; Lee, Sang-Myung; Kim, Hyung Sub; Shin, In Soo; Yao, Zhengsheng; Paik, Chang H.] NCI, Radiopharmaceut Lab, NIH, Bethesda, MD 20892 USA.
[Razjouyan, Faezeh; Wang, Shutao; Dreher, Matthew R.] NCI, Ctr Intervent Oncol Radiol & Imaging Sci, Clin Ctr, NIH, Bethesda, MD 20892 USA.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Paik, CH (reprint author), NCI, Radiopharmaceut Lab, NIH, Bethesda, MD 20892 USA.
EM cpaik@mail.nih.gov
FU Clinical Center, NIH; Center for Interventional Oncology, NIH
FX This research was supported by the intramural research program of
Clinical Center, NIH, and the Center for Interventional Oncology, NIH.
We thank Dr. Bradford Wood for his useful discussion and support of this
study. We also thank Dr. Insook Kim for her critical review and
editorial assistance of this manuscript.
NR 67
TC 0
Z9 0
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD MAY
PY 2012
VL 39
IS 4
BP 472
EP 483
DI 10.1016/j.nucmedbio.2011.10.020
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 939EP
UT WOS:000303790600004
ER
PT J
AU Haspel, RL
Atkinson, JB
Barr, FG
Kaul, KL
Leonard, DGB
O'Daniel, J
Rinder, HM
Scott, J
Sobel, ME
Speights, VO
AF Haspel, Richard L.
Atkinson, James B.
Barr, Frederic G.
Kaul, Karen L.
Leonard, Debra G. B.
O'Daniel, Julianne
Rinder, Henry M.
Scott, Joan
Sobel, Mark E.
Speights, V. O.
CA Training Residents Genomics Workin
TI TRIG on TRACK: educating pathology residents in genomic medicine
SO PERSONALIZED MEDICINE
LA English
DT Review
DE genomics; next-generation sequencing; pathology; post-graduate medical
education; residency training
ID HEALTH-CARE PROFESSIONALS; PERSONALIZED MEDICINE; INACTIVATING
MUTATIONS; AGENDA; ASSOCIATION; SIGNATURES; CARCINOMA; GENETICS; FUTURE
AB Genomic technologies are dramatically changing the practice of medicine. Next-generation sequencing has allowed prognostic stratification of cancer patients, personalized drug therapy and the identification of genetic risk factors for a multitude of diseases. As the physicians who oversee tissue- and laboratory-based diagnostic testing, pathologists must understand and utilize this new technology for the benefit of patients; however, only a minority of pathology residency programs currently provide training in genomics. In response to this urgent need, the Training Residents in Genomics (TRIG) Working Group has made significant progress towards creating, implementing, evaluating and disseminating a national curriculum in genomic pathology. Although presented in the context of pathology training, the approach described in this review can serve as model for education in genomic medicine of students, trainees or professionals in other areas of healthcare.
C1 [Atkinson, James B.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA.
[Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Kaul, Karen L.] N Shore Univ Hlth Syst, Dept Pathol & Lab Med, Evanston, IL USA.
[Leonard, Debra G. B.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
[O'Daniel, Julianne] Illumina Inc, San Diego, CA USA.
[Rinder, Henry M.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
[Scott, Joan] Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD USA.
[Sobel, Mark E.] Amer Soc Invest Pathol, Bethesda, MD USA.
[Speights, V. O.] Texas A&M Univ, Scott & White Mem Hosp, Dept Pathol, Hlth Sci Ctr, Temple, TX USA.
RP Haspel, RL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM rhaspel@bidmc.harvard.edu
NR 37
TC 6
Z9 6
U1 0
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD MAY
PY 2012
VL 9
IS 3
BP 287
EP 293
DI 10.2217/PME.12.6
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 937ZJ
UT WOS:000303702400008
ER
PT J
AU Boninger, ML
Brienza, D
Charlifue, S
Chen, YY
Curley, KC
Graves, DE
Groah, S
Heinemann, AW
Hudson, LM
Jackson, AB
Johnson, KL
Kalpakjian, CZ
Kusiak, A
Larson, KE
Agustin, TS
Sherwood, AM
Shinowara, N
Stripling, T
Tate, D
AF Boninger, M. L.
Brienza, D.
Charlifue, S.
Chen, Y-Y
Curley, K. C.
Graves, D. E.
Groah, S.
Heinemann, A. W.
Hudson, L. M.
Jackson, A. B.
Johnson, K. L.
Kalpakjian, C. Z.
Kusiak, A.
Larson, K. E.
Agustin, T. S.
Sherwood, A. M.
Shinowara, N.
Stripling, T.
Tate, D.
TI State of the Science Conference in Spinal Cord Injury Rehabilitation
2011: introduction
SO SPINAL CORD
LA English
DT Editorial Material
DE spinal cord injury; rehabilitation; research funding
ID MODEL SYSTEMS
C1 [Heinemann, A. W.] Northwestern Univ, Dept Phys Med & Rehabil, Ctr Rehabil Outcomes Res, Feinberg Sch Med,Rehabil Inst Chicago, Chicago, IL 60611 USA.
[Boninger, M. L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
[Boninger, M. L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA.
[Brienza, D.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Rehabil Engn Res Ctr Spinal Cord Injury, Pittsburgh, PA USA.
[Charlifue, S.] Craig Hosp, SCI Model Syst, Englewood, CO USA.
[Chen, Y-Y] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA.
[Curley, K. C.] USA, Telemed & Adv Technol Res Ctr, Med Res & Mat Command, ATTN MCMR RTC, Ft Detrick, MD USA.
[Curley, K. C.] Ctr Disaster & Humanitarian Assistance Med, Dept Sci & Med, Bethesda, MD USA.
[Curley, K. C.] Uniformed Serv Univ Hlth Sci, Dept Biomed Informat, Bethesda, MD 20814 USA.
[Curley, K. C.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA.
[Graves, D. E.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA.
[Groah, S.] Natl Rehabil Hosp, Washington, DC USA.
[Hudson, L. M.] Shepherd Ctr, SE Reg SCI Model Syst, Atlanta, GA USA.
[Jackson, A. B.] Univ Alabama Birmingham, Sch Med, Dept PM&R, Birmingham, AL USA.
[Johnson, K. L.] Univ Washington, Sch Med, Dept Rehabil Med, Div Rehabil Counseling, Seattle, WA 98195 USA.
[Kalpakjian, C. Z.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA.
[Kusiak, A.] US EPA, Off Res & Dev, Dept Vet Affairs, Washington, DC 20460 USA.
[Larson, K. E.] NSCIA, Elmhurst, NY USA.
[Agustin, T. S.] Natl Inst Disabil & Rehabil Res, OSERS US Dept Educ, Washington, DC USA.
[Sherwood, A. M.] Baylor Coll Med, Washington, DC USA.
[Shinowara, N.] NICHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD USA.
[Stripling, T.] Larkview Court, Fairfax Stn, VA USA.
[Tate, D.] Univ Michigan, Michigan Burlington Off Ctr, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA.
RP Heinemann, AW (reprint author), Northwestern Univ, Dept Phys Med & Rehabil, Ctr Rehabil Outcomes Res, Feinberg Sch Med,Rehabil Inst Chicago, 345 E Super St, Chicago, IL 60611 USA.
EM a-heinemann@northwestern.edu
RI Heinemann, Allen /K-6283-2012;
OI Heinemann, Allen /0000-0003-2782-7326; Sherwood,
Arthur/0000-0002-0110-4317; Boninger, Michael/0000-0001-6966-919X
FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153]
NR 2
TC 2
Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD MAY
PY 2012
VL 50
IS 5
SI SI
BP 342
EP 343
DI 10.1038/sc.2012.13
PG 2
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 938ZF
UT WOS:000303771700002
PM 22450887
ER
PT J
AU Boninger, M
French, J
Abbas, J
Nagy, L
Ferguson-Pell, M
Taylor, SJ
Rodgers, M
Saunders, N
Peckham, H
Marshall, R
Sherwood, A
AF Boninger, M.
French, J.
Abbas, J.
Nagy, L.
Ferguson-Pell, M.
Taylor, S. J.
Rodgers, M.
Saunders, N.
Peckham, H.
Marshall, R.
Sherwood, A.
TI Technology for mobility in SCI 10 years from now
SO SPINAL CORD
LA English
DT Article
DE spinal cord injury; mobility; assistive technology; International
Classification of Function
ID SPINAL-CORD-INJURY; VIRTUAL-REALITY; REHABILITATION; WALKING; DESIGN;
EXOSKELETONS; MULTICENTER; INTERFACE; MEDICINE; THERAPY
AB Objectives: To identify technological advances and that are likely to have a great impact on the quality of life and participation in individuals with spinal cord injury (SCI).
Methods: In this paper we use the International Classification of Function to frame a discussion on how technology is likely to impact SCI in 10 years. In addition, we discuss the implication of technological advances on future research.
Results/Conclusion: Although technology advances are exciting, a large challenge for the research community will be how to effectively apply and deploy this technology. Advances occurring in the next 10 years that reduce cost of technology may be more important to the population with SCI than brand new technologies. Social context is everything. As a research community we must advocate for better systems of care. Advocating now for better care will lead to a world in 2020 that is ready to adopt new technologies that are truly transformative. Spinal Cord (2012) 50, 358-363; doi:10.1038/sc.2011.165; published online 17 January 2012
C1 [Boninger, M.] UPMC Rehabil Inst, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
[Boninger, M.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA.
[French, J.] Neurotech Network, Tampa, FL USA.
[Abbas, J.] Arizona State Univ, Sch Biol & Hlth Syst Engn, Ctr Adapt Neural Syst, Tempe, AZ USA.
[Nagy, L.] MetroHlth Rehabil Inst Ohio, Community Advisory Board, Cleveland, OH USA.
[Ferguson-Pell, M.] Univ Alberta, Fac Rehabil Med, Edmonton, AB, Canada.
[Taylor, S. J.] Rehabil Inst Chicago, Chicago, IL 60611 USA.
[Rodgers, M.] Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA.
[Rodgers, M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Saunders, N.] Univ Melbourne, Dept Pharmacol, Parkville, Vic 3052, Australia.
[Peckham, H.] Case Western Reserve Univ, Dept Biomed Engn, Sch Med, Cleveland, OH 44106 USA.
[Peckham, H.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA.
[Marshall, R.] Univ Adelaide, Fac Hlth Sci, Sch Med, Adelaide, SA, Australia.
[Sherwood, A.] Natl Inst Disabil & Rehabil Res, US Dept Educ, Washington, DC USA.
RP Boninger, M (reprint author), UPMC Rehabil Inst, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA.
EM boninger@pitt.edu
OI Sherwood, Arthur/0000-0002-0110-4317; Saunders,
Norman/0000-0001-6660-7639; Boninger, Michael/0000-0001-6966-919X;
Abbas, James/0000-0002-3647-7041
NR 36
TC 3
Z9 3
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD MAY
PY 2012
VL 50
IS 5
SI SI
BP 358
EP 363
DI 10.1038/sc.2011.165
PG 6
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 938ZF
UT WOS:000303771700005
PM 22249329
ER
PT J
AU Bokkers, RPH
Hernandez, DA
Merino, JG
Mirasol, RV
van Osch, MJ
Hendrikse, J
Warach, S
Latour, LL
AF Bokkers, Reinoud P. H.
Hernandez, Daymara A.
Merino, Jose G.
Mirasol, Raymond V.
van Osch, Matthias J.
Hendrikse, Jeroen
Warach, Steven
Latour, Lawrence L.
CA Natl Inst Hlth Stroke Nat Hist Inv
TI Whole-Brain Arterial Spin Labeling Perfusion MRI in Patients With Acute
Stroke
SO STROKE
LA English
DT Article
DE acute stroke; cerebral hemodynamics; imaging; MRI; stroke management
ID NEPHROGENIC SYSTEMIC FIBROSIS; ACUTE ISCHEMIC-STROKE;
CEREBRAL-BLOOD-FLOW; TRANSIT-TIME; GADOLINIUM; INVERSION; SIGNAL; 3T
AB Background and Purpose-Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging.
Methods-Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion-perfusion mismatches.
Results-One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0-17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10-116] versus 114 [41-225] mL; P=0.01).
Conclusions-ASL can depict large perfusion deficits and perfusion-diffusion mismatches in correspondence with DSC. Our findings show that a fast 21/2-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents. (Stroke. 2012;43:1290-1294.)
C1 [Bokkers, Reinoud P. H.; Hendrikse, Jeroen] Univ Med Ctr Utrecht, Dept Radiol, NL-3584 CX Utrecht, Netherlands.
[Hernandez, Daymara A.; Merino, Jose G.; Mirasol, Raymond V.; Warach, Steven; Latour, Lawrence L.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD USA.
[van Osch, Matthias J.] Leiden Univ, CJ Gorter Ctr High Field MRI, Dept Radiol, Med Ctr, Leiden, Netherlands.
[Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA.
RP Bokkers, RPH (reprint author), Univ Med Ctr Utrecht, Dept Radiol, Heidelberglaan 100,HP E-01-132, NL-3584 CX Utrecht, Netherlands.
EM r.p.h.bokkers@umcutrecht.nl
OI Merino, Jose/0000-0002-6676-0008
FU Intramural Division of the National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda; Technology
Foundation STW, applied science division of The Netherlands Organisation
for Scientific Research; Dutch Ministry of Economic Affairs; Netherlands
Organization for Scientific Research [916-76-035]
FX This work was supported by the Intramural Division of the National
Institute of Neurological Disorders and Stroke, National Institutes of
Health, Bethesda, MD; Dr van Osch receives support from the Technology
Foundation STW, applied science division of The Netherlands Organisation
for Scientific Research, and the technology program of the Dutch
Ministry of Economic Affairs.; Dr Hendrikse receives support from the
Netherlands Organization for Scientific Research (grant 916-76-035).
NR 26
TC 43
Z9 47
U1 2
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2012
VL 43
IS 5
BP 1290
EP 1294
DI 10.1161/STROKEAHA.110.589234
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 936PO
UT WOS:000303602700028
PM 22426319
ER
PT J
AU Sanchez, R
Lee, TH
Wen, L
Montalvo, L
Schechterly, C
Colvin, C
Alter, HJ
Luban, NLC
Busch, MP
AF Sanchez, Rosa
Lee, Tzong-Hae
Wen, Li
Montalvo, Leilani
Schechterly, Cathy
Colvin, Camilla
Alter, Harvey J.
Luban, Naomi L. C.
Busch, Michael P.
TI Absence of transfusion-associated microchimerism in pediatric and adult
recipients of leukoreduced and gamma-irradiated blood components
SO TRANSFUSION
LA English
DT Article
ID VERSUS-HOST-DISEASE; POLYMERASE-CHAIN-REACTION; TRAUMA PATIENTS;
POSTOPERATIVE INFECTION; LYMPHOCYTE-RESPONSE; DONOR CELLS; SURVIVAL;
LONG; UPDATE; FETAL
AB BACKGROUND: Transfusion-associated microchimerism (TA-MC), the persistence of significant levels of donor white blood cells (WBCs) in blood recipients for prolonged periods, has been demonstrated after nonleukoreduced and leukoreduced transfusion to patients with severe traumatic injury. Development of TA-MC has not been rigorously studied in settings that do not involve massive trauma where the blood is leukoreduced and irradiated. STUDY DESIGN AND METHODS: A cohort of 409 prospectively followed medical and surgical adult and pediatric female recipients of leukoreduced and mostly irradiated allogeneic red blood cell and platelet transfusions were evaluated to determine development of TA-MC. Four- and 8-weeks-posttransfusion samples were analyzed using quantitative real-time polymerase chain reaction for Y-chromosome sequences in WBC DNA, the marker for microchimeric cells in female blood recipients. Repeat testing was performed on Y-chromosomepositive samples to confirm microchimerism (MC), and subsequent posttransfusion samples were tested to investigate persistence of MC. RESULTS: On initial testing, 40 of 207 (19%) adult and 44 of 202 (22%) pediatric female blood recipients demonstrated low-level MC. On repeat testing of these and additional specimens, 12 (3%) recipients demonstrated low-level transient MC, but none had persistent TA-MC similar to that seen in transfused trauma patients. CONCLUSION: Persistence of MC was not demonstrated in adult and pediatric recipients of leukoreduced and mostly irradiated blood components. The risk of TA-MC appears to be dependent on the clinical setting and is rare other than in patients sustaining severe traumatic injury.
C1 [Sanchez, Rosa] Blood Syst Res Inst, San Francisco, CA 94118 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Div Lab Med, Washington, DC 20052 USA.
Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
RP Sanchez, R (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA.
EM rsanchezrosen@bloodsystems.org
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[R01HL083388, R01HL67229]
FX This work was supported by Award Numbers R01HL083388 and R01HL67229 from
the National Heart, Lung, and Blood Institute, National Institutes of
Health. [Correction added after online publication 07-Oct-2011: Award
Numbers were updated.]
NR 45
TC 8
Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAY
PY 2012
VL 52
IS 5
BP 936
EP 945
DI 10.1111/j.1537-2995.2011.03366.x
PG 10
WC Hematology
SC Hematology
GA 940GB
UT WOS:000303876900005
PM 21981710
ER
PT J
AU Zeng, PB
Wang, JX
Huang, Y
Guo, XM
Li, JL
Wen, GX
Yang, TH
Yun, ZQ
He, M
Liu, Y
Yuan, YZ
Schulmann, J
Glynn, S
Ness, P
Jackson, JB
Shan, H
AF Zeng, Peibin
Wang, Jingxing
Huang, Yi
Guo, Xiaoming
Li, Julin
Wen, Guoxin
Yang, Tonghan
Yun, Zhongqiao
He, Miao
Liu, Yu
Yuan, Yuzhe
Schulmann, Jane
Glynn, Simone
Ness, Paul
Jackson, J. Brooks
Shan, Hua
CA NHLBI Retrovirus Epidemiology
TI The human immunodeficiency virus-1 genotype diversity and drug
resistance mutations profile of volunteer blood donors from Chinese
blood centers
SO TRANSFUSION
LA English
DT Article
ID REVERSE-TRANSCRIPTASE; SUBTYPE-B; ANTIRETROVIRAL THERAPY; 1-INFECTED
PATIENTS; EAST-ASIA; TYPE-1; HIV-1; PREVALENCE; PATTERNS; STRAINS
AB BACKGROUND: The global human immunodeficiency virus (HIV)-1 epidemic is becoming increasingly diverse and complex. Molecular epidemiologic characteristics were studied for HIV-1infected blood donors from five Chinese regions to determine genotype diversity and drug resistance mutations (DRMs) profile. STUDY DESIGN AND METHODS: HIV-1 confirmed-reactive serum samples were collected from 172 blood donors from five blood centers during 2007 to 2010. HIV-1 Pol including whole protease and partial reverse transcriptase genes was amplified, sequenced, and analyzed for the subtype determination and drug resistance profile description. RESULT: A total of 113 amplified sequences including 82 from Kunming blood center and 31 from four other blood centers had the following genotype characteristics: G (0.9%), B (2.7%), circulating recombinant form (CRF) 01_AE (32.7%), CRF07_BC (22.1%), and CRF08_BC (41.6%). Female donors represent 45.1% of all cases and 63.9% cases with DRMs. The prevalence of samples with potential low or higher resistance among Chinese blood donors is 4.4%. CONCLUSION: HIV-1 infection in Chinese blood donors is genetically diverse and the subtype distribution reflects that from the high-risk populations. Our results support continuous molecular epidemiologic surveillance for HIV-1 in blood donors as a part of a comprehensive HIV control program.
C1 [Wang, Jingxing] Chinese Acad Med Sci, Inst Blood Transfus, Chengdu 610052, Sichuan Provinc, Peoples R China.
Guangxi Blood Ctr, Liuzhou, Guangxi, Peoples R China.
Mianyang Blood Ctr, Mianyang, Sichuan, Peoples R China.
Urumqi City Blood Ctr, Urumqi, Xinjiang, Peoples R China.
Yunnan Kunming Blood Ctr, Kunming, Yunnan, Peoples R China.
Luoyang Blood Ctr, Luoyang, Henan, Peoples R China.
WESTAT Corp, Rockville, MD 20850 USA.
NHLBI, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Baltimore, MD USA.
RP Wang, JX (reprint author), Chinese Acad Med Sci, Inst Blood Transfus, 26 Hua Cai Rd, Chengdu 610052, Sichuan Provinc, Peoples R China.
EM jingxing_wang@vip.163.com
FU NHLBI Retroviral Epidemiology Donor Study-II [RFP-05-8067]
FX This work was supported by NHLBI Retroviral Epidemiology Donor Study-II
[RFP-05-8067].
NR 50
TC 13
Z9 15
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAY
PY 2012
VL 52
IS 5
BP 1041
EP 1049
DI 10.1111/j.1537-2995.2011.03415.x
PG 9
WC Hematology
SC Hematology
GA 940GB
UT WOS:000303876900016
PM 22044422
ER
PT J
AU Huvard, MJ
Schmid, P
Stroncek, DF
Flegel, WA
AF Huvard, Michael J.
Schmid, Pirmin
Stroncek, David F.
Flegel, Willy A.
TI Frequencies of SLC44A2 alleles encoding human neutrophil antigen-3
variants in the African American population
SO TRANSFUSION
LA English
DT Article
ID ACUTE LUNG INJURY; TRANSPORTER-LIKE PROTEIN-2; DONOR ANTIBODIES; TRALI;
5B
AB BACKGROUND: The human neutrophil antigen-3 (HNA-3) epitopes reside on the choline transporter-like protein-2 (CTL2). A single-nucleotide substitution (461G>A; Arg154Gln) on the CTL2 gene (SLC44A2) defines the allele SLC44A2*1, which expresses HNA-3a, and SLC44A2*2, which expresses HNA-3b; an additional substitution (457C>T; Leu153Phe) in SLC44A2*1:2 may impact genotyping systems. People who only express HNA-3b may develop anti-HNA-3a. These alloantibodies have been linked to severe transfusion-related acute lung injury, which may be a reason to screen blood donors for SLC44A2*2 homozygosity. For Caucasian and Asian populations, SLC44A2 allele frequencies are known. Our primary objective was to determine the SLC44A2 allele frequencies in the African American population. STUDY DESIGN AND METHODS: Purified DNA from 334 individuals (202 male, 132 female; 241 African American, 93 Caucasian) was collected. Two real-time polymerase chain reaction assays were developed to genotype all samples; results were confirmed by nucleotide sequencing. RESULTS: In 241 African American donors, the allele frequency of SLC44A2*1 was 93% (85%-<100%; 95% confidence intervals, Poisson distribution) while SLC44A2*2 was 7% (5%-10%). In 93 Caucasian donors, the allele frequency of SLC44A2*1 was 83% (71%-98%) and SLC44A2*2 was 17% (11%-24%), matching previously reported data for Caucasians but differing from African Americans (p < 0.001, Fisher's exact test). CONCLUSIONS: This study describes the allele frequencies of the three known HNA-3 variants in an African American population. We found that African Americans have a significantly lower probability of possessing the SLC44A2*2 allele and may thus be less likely to form the clinically relevant anti-HNA-3a.
C1 [Flegel, Willy A.] NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
FU NIH Clinical Center
FX This research was supported by the Intramural Research Program of the
NIH Clinical Center.
NR 23
TC 10
Z9 12
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAY
PY 2012
VL 52
IS 5
BP 1106
EP 1111
DI 10.1111/j.1537-2995.2011.03396.x
PG 6
WC Hematology
SC Hematology
GA 940GB
UT WOS:000303876900024
PM 22040064
ER
PT J
AU Chalancon, G
Ravarani, CNJ
Balaji, S
Martinez-Arias, A
Aravind, L
Jothi, R
Babu, MM
AF Chalancon, Guilhem
Ravarani, Charles N. J.
Balaji, S.
Martinez-Arias, Alfonso
Aravind, L.
Jothi, Raja
Babu, M. Madan
TI Interplay between gene expression noise and regulatory network
architecture
SO TRENDS IN GENETICS
LA English
DT Review
DE expression noise; gene regulatory network; persistence; phenotypic
variation; single-cell analysis; differentiation; development
ID DETERMINES CELL FATE; ESCHERICHIA-COLI; SINGLE-CELL; GENOMIC ANALYSIS;
DYNAMICS; VARIABILITY; TRANSCRIPTION; EVOLUTION; SELECTION; YEAST
AB Complex regulatory networks orchestrate most cellular processes in biological systems. Genes in such networks are subject to expression noise, resulting in isogenic cell populations exhibiting cell-to-cell variation in protein levels. Increasing evidence suggests that cells have evolved regulatory strategies to limit, tolerate or amplify expression noise. In this context, fundamental questions arise: how can the architecture of gene regulatory networks generate, make use of or be constrained by expression noise? Here, we discuss the interplay between expression noise and gene regulatory network at different levels of organization, ranging from a single regulatory interaction to entire regulatory networks. We then consider how this interplay impacts a variety of phenomena, such as pathogenicity, disease, adaptation to changing environments, differential cell-fate outcome and incomplete or partial penetrance effects. Finally, we highlight recent technological developments that permit measurements at the single-cell level, and discuss directions for future research.
C1 [Chalancon, Guilhem; Ravarani, Charles N. J.; Babu, M. Madan] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
[Balaji, S.] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Balaji, S.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Balaji, S.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Martinez-Arias, Alfonso] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Chalancon, G (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM guilhem@mrc-lmb.cam.ac.uk; madanm@mrc-lmb.cam.ac.uk
RI Martinez Arias, Alfonso/F-1966-2010; Jothi, Raja/G-3780-2015
FU Gates Cambridge Scholarship; Knox Trinity studentship; AFR; Medical
Research Council; EMBO; HFSP [RGY0073/2010]; European Research Council;
NIH, National Institute of Environmental Health Sciences
[1ZIAES102625-03]; NLM, NCBI
FX We thank Mania Buljan, Kai Kruse, Elizabeth Ing-Simmons and Andrew
Deonarine for helpful remarks. This work was supported by the Gates
Cambridge Scholarship and the Knox Trinity studentship (G.C.), the AFR
Grant Scheme (C.N.J.R.), the Medical Research Council (G.C., C.N.J.R.
and M.M.B.), EMBO young investigator program, HFSP (RGY0073/2010;
M.M.B.), European Research Council (AM.-A.) and the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(RJ: 1ZIAES102625-03) and NLM, NCBI (L.A.).
NR 125
TC 74
Z9 75
U1 5
U2 70
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD MAY
PY 2012
VL 28
IS 5
BP 221
EP 232
DI 10.1016/j.tig.2012.01.006
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 937BU
UT WOS:000303634800004
PM 22365642
ER
PT J
AU Shuch, B
Singer, EA
Bratslavsky, G
AF Shuch, Brian
Singer, Eric A.
Bratslavsky, Gennady
TI The Surgical Approach to Multifocal Renal Cancers: Hereditary Syndromes,
Ipsilateral Multifocality, and Bilateral Tumors
SO UROLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Renal cell carcinoma; Bilateral kidney cancer; Multifocal kidney cancer;
Hereditary kidney cancer
ID HOGG-DUBE-SYNDROME; NEPHRON-SPARING SURGERY; HIPPEL-LINDAU-DISEASE;
TUBEROUS SCLEROSIS COMPLEX; GENOME-WIDE ASSOCIATION; CELL-CARCINOMA;
PARTIAL NEPHRECTOMY; RADICAL NEPHRECTOMY; SIMPLE ENUCLEATION; UTERINE
FIBROIDS
AB Although the management of sporadic renal tumors is challenging enough, dealing with those with bilateral, multifocal, and hereditary kidney cancer adds an additional level of complexity. A clinician managing this patient population must understand the hereditary syndromes and the genetic testing available. Treating physicians must be familiar with enucleative surgery, complex or multiple tumor partial nephrectomy, complex renal reconstruction, re-operative renal surgery, and active surveillance strategies. With proper management, most patients affected with bilateral, multifocal, or hereditary RCC can have a long life expectancy while maintaining adequate renal function.
C1 [Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
[Shuch, Brian; Singer, Eric A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA.
EM bratslag@upstate.edu
NR 120
TC 14
Z9 16
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0094-0143
J9 UROL CLIN N AM
JI Urol. Clin. N. Am.
PD MAY
PY 2012
VL 39
IS 2
BP 133
EP +
DI 10.1016/j.ucl.2012.01.006
PG 17
WC Urology & Nephrology
SC Urology & Nephrology
GA 941EO
UT WOS:000303946700004
PM 22487757
ER
PT J
AU Siggeirsdottir, K
Aspelund, T
Jonsson, BY
Mogensen, B
Launer, LJ
Harris, TB
Sigurdsson, G
Gudnason, V
AF Siggeirsdottir, Kristin
Aspelund, Thor
Jonsson, Brynjolfur Y.
Mogensen, Brynjolfur
Launer, Lenore J.
Harris, Tamara B.
Sigurdsson, Gunnar
Gudnason, Vilmundur
TI Effect of vertebral fractures on function, quality of life and
hospitalisation the AGES-Reykjavik study
SO AGE AND AGEING
LA English
DT Article
DE vertebral fracture; health burden; osteoporotic fracture; strength; ADL;
quality of life; mobility; elderly
ID OSTEOPOROTIC FRACTURES; WOMEN; HEALTH; RISK; MEN; DISABILITY;
EPIDEMIOLOGY; PREVALENCE; MORTALITY; OUTCOMES
AB Objective: assess the effect of clinical vertebral and other osteoporotic fractures on function and the subsequent risk of hospitalisation.
Design: individuals from the prospective population-based cohort study Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were examined between 2002 and 2006 and followed up for 5.4 years.
Subjects: a total of 5,764 individuals, 57.7% women, born 1907-35, mean age 77.
Method: four groups with a verified fracture status were used; vertebral fractures, other osteoporotic fractures excluding vertebral, non-osteoporotic fractures and not-fractured were compared and analysed for the effect on mobility, strength, QoL, ADL, co-morbidity and hospitalisation.
Results: worst performance on functional tests was in the vertebral fracture group for women (P < 0.0001) and the other osteoporotic fractures group for men (P < 0.05). Both vertebral and other osteoporotic fractures, showed an increased risk of hospitalisation, HR = 1.4 (95% CI: 1.3-1.7) and 1.2 (95% CI: 1.1-1.2) respectively (P < 0.0001). Individuals with vertebral fractures had 50% (P < 0.0001) longer hospitalisation than not-fractured and 33% (P < 0.002) longer than the other osteoporotic fractures group.
Conclusion: individuals with a history of clinical vertebral fracture seem to carry the greatest health burden compared with other fracture groups, emphasising the attention which should be given to those individuals.
C1 [Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Jonsson, Brynjolfur Y.] Malmo Univ Hosp, Dept Orthopead, Malmo, Sweden.
[Mogensen, Brynjolfur; Sigurdsson, Gunnar] Landspitalinn Univ Hosp, Reykjavik, Iceland.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MA USA.
[Aspelund, Thor; Mogensen, Brynjolfur; Sigurdsson, Gunnar; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
RP Siggeirsdottir, K (reprint author), Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
EM kristin@hjarta.is
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
FU National Institutes of Health, USA [N01-AG-12100]; National Institute on
Aging; Hjartavernd (The Icelandic Heart Association); Althingi (The
Icelandic Parliament)
FX This study was funded by the National Institutes of Health, USA contract
N01-AG-12100, the National Institute on Aging Intramural Research
Program, Hjartavernd (The Icelandic Heart Association) and the Althingi
(The Icelandic Parliament).
NR 30
TC 6
Z9 6
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
J9 AGE AGEING
JI Age Ageing
PD MAY
PY 2012
VL 41
IS 3
BP 351
EP 357
DI 10.1093/ageing/afs003
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 933BU
UT WOS:000303335000013
PM 22367357
ER
PT J
AU Chen, WZ
Dimitrov, DS
AF Chen, Weizao
Dimitrov, Dimiter S.
TI Monoclonal Antibody-Based Candidate Therapeutics Against HIV Type 1
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Review
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES;
SINGLE-CHAIN ANTIBODY; N-TRIMER REGION; ENVELOPE GLYCOPROTEINS;
PASSIVE-IMMUNIZATION; IN-VITRO; SYNERGISTIC NEUTRALIZATION; CD4-BINDING
SITE; RHESUS-MONKEYS
AB Treatment of HIV-1 infection has been highly successful with small molecule drugs. However, resistance still develops. In addition, long-term use can lead to toxicity with unpredictable effects on health. Finally, current drugs do not lead to HIV-1 eradication. The presence of the virus leads to chronic inflammation, which can result in increased morbidity and mortality after prolonged periods of infection. Monoclonal antibodies (mAbs) have been highly successful during the past two decades for therapy of many diseases, primarily cancers and immune disorders. They are relatively safe, especially human mAbs that have evolved in humans at high concentrations to fight diseases and long-term use may not lead to toxicities. Several broadly neutralizing mAbs (bnmAbs) against HIV-1 can protect animals but are not effective when used for therapy of an established infection. We have hypothesized that HIV-1 has evolved strategies to effectively escape neutralization by full-size antibodies in natural infections but not by smaller antibody fragments. Therefore, a promising direction of research is to discover and exploit antibody fragments as potential candidate therapeutics against HIV-1. Here we review several bnmAbs and engineered antibody domains (eAds), their in vitro and in vivo antiviral efficacy, mechanisms used by HIV-1 to escape them, and strategies that could be effective to develop more powerful mAb-based HIV-1 therapeutics.
C1 [Chen, Weizao] NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA.
RP Chen, WZ (reprint author), NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Miller Dr Bldg 469,Room 144, Frederick, MD 21702 USA.
EM chenw3@mail.nih.gov
FU National Institutes of Health (NIH); National Cancer Institute; Center
for Cancer Research; Gates Foundation
FX We thank John Owens and Emily Streaker from our group for technical
assistance and helpful comments. This project was supported by the
Intramural AIDS Targeted Antiviral Program of the National Institutes of
Health (NIH), by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research, and by the Gates
Foundation (D.S.D.).
NR 87
TC 5
Z9 5
U1 0
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 2012
VL 28
IS 5
BP 425
EP 434
DI 10.1089/aid.2011.0226
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 933XY
UT WOS:000303401500001
PM 21827278
ER
PT J
AU Plaeger, SF
Collins, BS
Musib, R
Deeks, SG
Read, S
Embry, A
AF Plaeger, Susan F.
Collins, Brenda S.
Musib, Runa
Deeks, Steven G.
Read, Sarah
Embry, Alan
TI Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A
Workshop Summary
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; PLASMACYTOID DENDRITIC
CELLS; SIV INFECTION; ANTIRETROVIRAL THERAPY; SYSTEM ACTIVATION; TYPE-1
INFECTION; PROGNOSTIC VALUE; MEMORY; AIDS
AB With the advent of highly effective antiretroviral therapy (ART), infection with human immunodeficiency virus (HIV) has become a chronic disease rather than a death sentence. Nevertheless, effectively treated individuals have a higher than normal risk for developing noninfectious comorbidities, including cardiovascular and renal disease. Although traditional risk factors of aging as well as treatment toxicity contribute to this risk, many investigators consider chronic HIV-associated inflammation a significant factor in such end-organ disease. Despite effective viral suppression, chronic inflammation persists at levels higher than in uninfected people, yet the stimuli for the inflammation and the mechanism by which inflammation persists and promotes disease pathology remain incompletely understood. This critical gap in scientific understanding complicates and hampers effective decision making about appropriate medical intervention. To better understand the mechanism(s) of chronic immune activation in treated HIV disease, three questions need answers: (1) what is the cause of persistent immune activation during treated HIV infection, (2) what are the best surrogate markers of chronic immune activation in this setting, and (3) what therapeutic intervention(s) could prevent or reverse this process? The NIH sponsored and convened a meeting to discuss the state of knowledge concerning these questions and the best course for developing effective therapeutic strategies. This report summarizes the findings of that NIH meeting.
C1 [Plaeger, Susan F.; Read, Sarah; Embry, Alan] NIAID, Basic Sci Program, Div Aids, NIH,HHS, Bethesda, MD 20892 USA.
[Collins, Brenda S.] NIAID, Henry M Jackson Fdn Advancement Mil Med, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Musib, Runa] Henry M Jackson Fdn Advancement Mil Med, US Mil HIV Res Program, Rockville, MD USA.
[Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Plaeger, SF (reprint author), NIAID, Basic Sci Program, Div Aids, NIH,HHS, 6700-B Rockledge Dr,Room 4101, Bethesda, MD 20892 USA.
EM splaeger@niaid.nih.gov
FU National Institute of Allergies and Infectious Diseases; National
Institutes of Health; Department of Health and Human Services
[HHSN272200800012C]
FX This project has been funded in whole or in part with Federal funds from
the National Institute of Allergies and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
Contract No. HHSN272200800012C.
NR 63
TC 26
Z9 28
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 2012
VL 28
IS 5
BP 469
EP 477
DI 10.1089/aid.2011.0213
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 933XY
UT WOS:000303401500008
PM 21854232
ER
PT J
AU Ng, OT
Eyzaguirre, LM
Carr, JK
Chew, KK
Lin, L
Chua, A
Leo, YS
Redd, AD
Quinn, TC
Laeyendecker, O
AF Ng, Oon Tek
Eyzaguirre, Lindsay M.
Carr, Jean K.
Chew, Kuan Kiat
Lin, Li
Chua, Arlene
Leo, Yee Sin
Redd, Andrew D.
Quinn, Thomas C.
Laeyendecker, Oliver
TI Identification of New CRF51_01B in Singapore Using Full Genome Analysis
of Three HIV Type 1 Isolates
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID CIRCULATING RECOMBINANT FORM; THAILAND; CRF15-01B; CRF33-01B; SEQUENCE;
MALAYSIA
AB A recent HIV-1 molecular epidemiology survey in Singapore identified a novel CRF01_AE/B recombinant form, which accounted for 13 (11.9%) of 109 patient samples. Peripheral blood mononuclear cell DNA from three of these 13 patients was used to generate near full-length sequences to characterize the novel CRF01_AE/B recombinant form. The three isolates had a recombinant structure composed of CRF01_AE and subtype B, and shared identical breakpoints. As the three patients were not epidemiologically linked, this recombinant form has been designated CRF51_01B. Identification of the novel recombinant forms indicates ongoing active HIV-1 transmission in Singapore.
C1 [Ng, Oon Tek; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Med Inst, Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
[Ng, Oon Tek; Chew, Kuan Kiat; Lin, Li; Chua, Arlene; Leo, Yee Sin] Tan Tock Seng Hosp, Dept Infect Dis, Singapore, Singapore.
[Eyzaguirre, Lindsay M.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Redd, Andrew D.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
RP Ng, OT (reprint author), Johns Hopkins Univ, Sch Med, Rangos Bldg,Room 527,855 N Wolfe St, Baltimore, MD 21205 USA.
EM oong@jhsph.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760; Chua,
Arlene/0000-0001-6428-9083
FU Division of Intramural Research; NIAID; NIH; Singapore National Medical
Research Training Fellowship
FX A Singapore National Medical Research Training Fellowship grant provided
salary support for O.T. Ng. We acknowledge the physicians, staff, and
patients of the outpatient service at the Communicable Disease Centre,
Singapore, who made this study possible. Additional support was provided
by the Division of Intramural Research, NIAID, NIH. We thank Dr. Mark I.
C. Chen, Mr. Ridzwan Abdullah, and Ms. Tan Pei Ling for help with
patient recruitment and sample collection. O.T.N. and L.M.E. contributed
equally to this work. The sequences analyzed in this study have been
deposited in GenBank under accession numbers JN029801, JN029802, and
JN029803.
NR 12
TC 25
Z9 25
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 2012
VL 28
IS 5
BP 527
EP 530
DI 10.1089/aid.2011.0177
PG 4
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 933XY
UT WOS:000303401500015
PM 21902588
ER
PT J
AU Delis, F
Benveniste, H
Xenos, M
Grandy, D
Wang, GJ
Volkow, ND
Thanos, PK
AF Delis, Foteini
Benveniste, Helene
Xenos, Michalis
Grandy, David
Wang, Gene-Jack
Volkow, Nora D.
Thanos, Panayotis K.
TI Loss of Dopamine D2 Receptors Induces Atrophy in the Temporal and
Parietal Cortices and the Caudal Thalamus of Ethanol-Consuming Mice
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE D2 Receptors; Ethanol; Brain; MRI; Mouse
ID PRENATAL ALCOHOL EXPOSURE; MATTER VOLUME LOSS; GRAY-MATTER; HIPPOCAMPAL
VOLUME; AGONISTS PROTECT; HEAVY DRINKING; DEFICIENT MICE; BRAIN VOLUMES;
DEPENDENCE; INDIVIDUALS
AB Background: The need of an animal model of alcoholism becomes apparent when we consider the genetic diversity of the human populations, an example being dopamine D2 receptor (DRD2) expression levels. Research suggests that low DRD2 availability is associated with alcohol abuse, while higher DRD2 levels may be protective against alcoholism. This study aims to establish whether (i) the ethanol-consuming mouse is a suitable model of alcohol-induced brain atrophy and (ii) DRD2 protect the brain against alcohol toxicity. Methods: Adult Drd2+/+ and Drd2-/- mice drank either water or 20% ethanol solution for 6 months. At the end of the treatment period, the mice underwent magnetic resonance (MR) imaging under anesthesia. MR images were registered to a common space, and regions of interest were manually segmented. Results: We found that chronic ethanol intake induced a decrease in the volume of the temporal and parietal cortices as well as the caudal thalamus in Drd2-/- mice. Conclusions: The result suggests that (i) normal DRD2 expression has a protective role against alcohol-induced brain atrophy and (ii) in the absence of Drd2 expression, prolonged ethanol intake reproduces a distinct feature of human brain pathology in alcoholism, the atrophy of the temporal and parietal cortices.
C1 [Delis, Foteini; Wang, Gene-Jack; Thanos, Panayotis K.] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Delis, Foteini; Volkow, Nora D.; Thanos, Panayotis K.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA.
[Benveniste, Helene] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA.
[Xenos, Michalis] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Grandy, David] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
[Thanos, Panayotis K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA.
EM thanos@bnl.gov
OI Xenos, Michalis/0000-0001-8441-1306
FU NIAAA [AA 11034, AA07574, AA07611]
FX This work was supported by the NIAAA (AA 11034 & AA07574, AA07611). We
thank Vanessa Gopez for care of the animals, Michael Michaelides for MRI
scheduling, and Yu Ma for suggestions on MRI analysis.
NR 67
TC 5
Z9 5
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAY
PY 2012
VL 36
IS 5
BP 815
EP 825
DI 10.1111/j.1530-0277.2011.01667.x
PG 11
WC Substance Abuse
SC Substance Abuse
GA 933UJ
UT WOS:000303388500009
PM 22017419
ER
PT J
AU Bongard, RD
Myers, CR
Lindemer, BJ
Baumgardt, S
Gonzalez, FJ
Merker, MP
AF Bongard, Robert D.
Myers, Charles R.
Lindemer, Brian J.
Baumgardt, Shelley
Gonzalez, Frank J.
Merker, Marilyn P.
TI Coenzyme Q(1) as a probe for mitochondrial complex I activity in the
intact perfused hyperoxia-exposed wild-type and Nqo1-null mouse lung
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE pulmonary circulation; quinone; knockout mice; isolated perfused mouse
lung; NAD(P)H:quinone oxidoreductase 1; mass spectrometry
ID ARTERIAL ENDOTHELIAL-CELLS; PULMONARY-CIRCULATION; SUBMITOCHONDRIAL
PARTICLES; OXIDATIVE-PHOSPHORYLATION; DUROQUINONE REDUCTION;
ELECTRON-TRANSPORT; OXIDOREDUCTASE 1; INJURY SURVIVAL; MICE; NAD(P)H
AB Bongard RD, Myers CR, Lindemer BJ, Baumgardt S, Gonzalez FJ, Merker MP. Coenzyme Q1 as a probe for mitochondrial complex I activity in the intact perfused hyperoxia-exposed wild-type and Nqo1-null mouse lung. Am J Physiol Lung Cell Mol Physiol 302: L949-L958, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00251.2011.-Previous studies showed that coenzyme Q(1) (CoQ(1)) reduction on passage through the rat pulmonary circulation was catalyzed by NAD(P) H: quinone oxidoreductase 1 (NQO1) and mitochondrial complex I, but that NQO1 genotype was not a factor in CoQ(1) reduction on passage through the mouse lung. The aim of the present study was to evaluate the complex I contribution to CoQ(1) reduction in the isolated perfused wild-type (NQO1(+/+)) and Nqo1-null (NQO1(-/-))mouse lung. CoQ(1) reduction was measured as the steady-state pulmonary venous CoQ(1) hydroquinone (CoQ(1)H(2)) efflux rate during infusion of CoQ(1) into the pulmonary arterial inflow. CoQ(1)H(2) efflux rates during infusion of 50 mu M CoQ(1) were not significantly different for NQO1(+/+) and NQO1(-)/(-) lungs (0.80 +/- 0.03 and 0.68 +/- 0.07 mu mol.min(-1).g lung dry wt(-1), respectively, P > 0.05). The mitochondrial complex I inhibitor rotenone depressed CoQ(1)H(2) efflux rates for both genotypes (0.19 +/- 0.08 and 0.08 +/- 0.04 mu mol.min(-1).g lung dry wt(-1) for NQO1(+/+) and NQO1(-/-), respectively, P < 0.05). Exposure of mice to 100% O-2 for 48 h also depressed CoQ(1)H(2) efflux rates in NQO1(+/+) and NQO1 (-/-) lungs (0.43 +/- 0.03 and 0.11 +/- 0.04 mu mol.min(-1).g lung dry wt(-1), respectively, P < 0.05 by ANOVA). The impact of rotenone or hyperoxia on CoQ(1) redox metabolism could not be attributed to effects on lung wet-to-dry weight ratios, perfusion pressures, perfused surface areas, or total venous effluent CoQ(1) recoveries, the latter measured by spectrophotometry or mass spectrometry. Complex I activity in mitochondria-enriched lung fractions was depressed in hyperoxia-exposed lungs for both genotypes. This study provides new evidence for the potential utility of CoQ(1) as a nondestructive indicator of the impact of pharmacological or pathological exposures on complex I activity in the intact perfused mouse lung.
C1 [Merker, Marilyn P.] Zablocki Vet Affairs Med Ctr, Milwaukee, WI 53295 USA.
[Bongard, Robert D.] Med Coll Wisconsin, Dept Pulm Med, Milwaukee, WI 53295 USA.
[Myers, Charles R.; Merker, Marilyn P.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53295 USA.
[Lindemer, Brian J.; Baumgardt, Shelley; Merker, Marilyn P.] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53295 USA.
[Gonzalez, Frank J.] Natl Canc Inst, Milwaukee, WI 53295 USA.
RP Merker, MP (reprint author), Zablocki VAMC, Med Coll Wisconsin, Res Serv 151, Milwaukee, WI 53295 USA.
EM mmerker@mcw.edu
OI Myers, Charles/0000-0001-7956-3217
FU Department of Veterans Affairs (VA); National Cancer Institute
FX This work was supported by the Department of Veterans Affairs (VA
Medical Research Funds) and the National Cancer Institute Intramural
Research Program.
NR 53
TC 3
Z9 3
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD MAY
PY 2012
VL 302
IS 9
BP L949
EP L958
DI 10.1152/ajplung.00251.2011
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 936TW
UT WOS:000303613900015
PM 22268123
ER
PT J
AU Phillips, D
Covian, R
Aponte, AM
Glancy, B
Taylor, JF
Chess, D
Balaban, RS
AF Phillips, Darci
Covian, Raul
Aponte, Angel M.
Glancy, Brian
Taylor, Joni F.
Chess, David
Balaban, Robert S.
TI Regulation of oxidative phosphorylation complex activity: effects of
tissue-specific metabolic stress within an allometric series and acute
changes in workload
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE mitochondria; cytochrome oxidase; Complex V; F1-F0ATPase; oxygen
consumption; energy metabolism; heart; liver; murine; porcine; rabbit;
native gel electrophoresis; mass spectrometry; posttranslational
modifications; phosphorylation
ID CYTOCHROME-C-OXIDASE; PYRUVATE-DEHYDROGENASE ACTIVITY; MITOCHONDRIAL ATP
SYNTHASE; OXYGEN-CONSUMPTION; PROTEIN-PHOSPHORYLATION;
ENERGY-METABOLISM; CALCIUM-IONS; ELECTRON-TRANSFER; SKELETAL-MUSCLE;
RABBIT HEART
AB Phillips D, Covian R, Aponte AM, Glancy B, Taylor JF, Chess D, Balaban RS. Regulation of oxidative phosphorylation complex activity: effects of tissue-specific metabolic stress within an allometric series and acute changes in workload. Am J Physiol Regul Integr Comp Physiol 302: R1034-R1048, 2012. First published February 29, 2012; doi: 10.1152/ajpregu.00596.2011.-The concentration of mitochondrial oxidative phosphorylation complexes (MOPCs) is tuned to the maximum energy conversion requirements of a given tissue; however, whether the activity of MOPCs is altered in response to acute changes in energy conversion demand is unclear. We hypothesized that MOPCs activity is modulated by tissue metabolic stress to maintain the energy-metabolism homeostasis. Metabolic stress was defined as the observed energy conversion rate/maximum energy conversion rate. The maximum energy conversion rate was assumed to be proportional to the concentration of MOPCs, as determined with optical spectroscopy, gel electrophoresis, and mass spectrometry. The resting metabolic stress of the heart and liver across the range of resting metabolic rates within an allometric series (mouse, rabbit, and pig) was determined from MPOCs content and literature respiratory values. The metabolic stress of the liver was high and nearly constant across the allometric series due to the proportional increase in MOPCs content with resting metabolic rate. In contrast, the MOPCs content of the heart was essentially constant in the allometric series, resulting in an increasing metabolic stress with decreasing animal size. The MOPCs activity was determined in native gels, with an emphasis on Complex V. Extracted MOPCs enzyme activity was proportional to resting metabolic stress across tissues and species. Complex V activity was also shown to be acutely modulated by changes in metabolic stress in the heart, in vivo and in vitro. The modulation of extracted MOPCs activity suggests that persistent posttranslational modifications (PTMs) alter MOPCs activity both chronically and acutely, specifically in the heart. Protein phosphorylation of Complex V was correlated with activity inhibition under several conditions, suggesting that protein phosphorylation may contribute to activity modulation with energy metabolic stress. These data are consistent with the notion that metabolic stress modulates MOPCs activity in the heart.
C1 [Phillips, Darci; Covian, Raul; Glancy, Brian; Taylor, Joni F.; Chess, David; Balaban, Robert S.] NHLBI, Lab Cardiac Energet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Aponte, Angel M.] NHLBI, Prote Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, Lab Cardiac Energet, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room B1D-416,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsb@nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
FU National Institutes of Health Division of Intramural Research
FX This work was supported by the National Institutes of Health Division of
Intramural Research.
NR 92
TC 27
Z9 29
U1 0
U2 3
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 MAY
PY 2012
VL 302
IS 9
BP R1034
EP R1048
DI 10.1152/ajpregu.00596.2011
PG 15
WC Physiology
SC Physiology
GA 935UQ
UT WOS:000303547500002
PM 22378775
ER
PT J
AU Aravindhan, V
Mohan, V
Surendar, J
Rao, MM
Anuradha, R
Deepa, M
Babu, S
AF Aravindhan, Vivekanandhan
Mohan, Viswanathan
Surendar, Jayagopi
Rao, Maradana Muralidhara
Anuradha, Rajamanickam
Deepa, Mohan
Babu, Subash
TI Effect of Filarial Infection on Serum Inflammatory and Atherogenic
Biomarkers in Coronary Artery Disease (CURES-121)
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID URBAN-RURAL-EPIDEMIOLOGY; INTIMAL MEDIAL THICKNESS; LYMPHATIC
FILARIASIS; DECREASED PREVALENCE; HYGIENE HYPOTHESIS; ATHEROSCLEROSIS;
ADIPOCYTOKINES; ASSOCIATION; MORTALITY; HELMINTHS
AB Helminth infections can potentially confer protection against metabolic disorders, possibly through immunomodulation. In this study, the baseline prevalence of lymphatic filariasis (LF) among subjects without (AT = 236) and with (N = 217) coronary artery disease (CAD) was examined as part of the Chennai Urban Rural Epidemiological Study (CURES). The prevalence of LF was not significantly different between CAD(-) and CAD(+) subjects. The LF antigen load and antibody levels indicated comparable levels of infection and exposure between the groups. Within the CAD group, LF+ and LF- subjects had no significant difference in the intimal medial thickness and high-sensitivity C-reactive protein values. However, LF infection was associated with augmented levels of tumor necrosis factor-a and interleukin-6 among CAD(+) subjects. The LF infection had no effect on serum adipocytokine profile. In conclusion, unlike type-2 diabetes, there is no association between the prevalence of LF and CAD and also no evidence of protective immunomodulation of LF infection on CAD in the Asian Indian population.
C1 [Aravindhan, Vivekanandhan] Anna Univ, Lab Mol Immunol, AU KBC Res Ctr, Madras 600044, Tamil Nadu, India.
[Mohan, Viswanathan; Surendar, Jayagopi; Rao, Maradana Muralidhara; Deepa, Mohan] Madras Diabet Res Fdn, Madras, Tamil Nadu, India.
Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India.
[Anuradha, Rajamanickam; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, TB Res Ctr, Madras, Tamil Nadu, India.
[Babu, Subash] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Aravindhan, V (reprint author), Anna Univ, Lab Mol Immunol, AU KBC Res Ctr, MIT Campus, Madras 600044, Tamil Nadu, India.
EM cvaravindhan@yahoo.co.uk; drmohans@vsnl.net; surendarj85@gmail.com;
raoinfoster@gmail.com; anuvenil@gmail.com; deepa.mohan1@gmail.com;
sbabu@mail.nih.gov
OI Aravindhan, Vivekanandhan/0000-0002-5639-4948
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, through the
NIAID/TRC ICER; KB Chandrasekhar Research Foundation, India
FX This work received partial support from the Intramural Research Program
of the Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, through the
NIAID/TRC ICER program and KB Chandrasekhar Research Foundation, India.
NR 29
TC 2
Z9 2
U1 0
U2 2
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 MAY
PY 2012
VL 86
IS 5
BP 828
EP 833
DI 10.4269/ajtmh.2012.11-0773
PG 6
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 935WY
UT WOS:000303554100017
PM 22556082
ER
PT J
AU Hartley, DM
Barker, CM
Le Menach, A
Niu, TC
Gaff, HD
Reisen, WK
AF Hartley, David M.
Barker, Christopher M.
Le Menach, Arnaud
Niu, Tianchan
Gaff, Holly D.
Reisen, William K.
TI Effects of Temperature on Emergence and Seasonality of West Nile Virus
in California
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID CULEX-TARSALIS DIPTERA; LOUIS-ENCEPHALITIS-VIRUS; KERN COUNTY;
SOUTHEASTERN CALIFORNIA; HOST-SEEKING; TRANSMISSION; CULICIDAE; BIRDS;
MODEL; INFECTION
AB Temperature has played a critical role in the spatiotemporal dynamics of West Nile virus transmission throughout California from its introduction in 2003 through establishment by 2009. We compared two novel mechanistic measures of transmission risk, the temperature-dependent ratio of virus extrinsic incubation period to the mosquito gonotrophic period (BT), and the fundamental reproductive ratio (R-0) based on a mathematical model, to analyze spatiotemporal patterns of receptivity to viral amplification. Maps of BT and R-0 were created at 20-km scale and compared throughout California to seroconversions in sentinel chicken flocks at half-month intervals. Overall, estimates of BT and R-0 agreed with intensity of transmission measured by the frequency of sentinel chicken seroconversions. Mechanistic measures such as these are important for understanding how temperature affects the spatiotemporal dynamics of West Nile virus transmission and for delineating risk estimates useful to inform vector control agency intervention decisions and communicate outbreak potential.
C1 [Hartley, David M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA.
Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20057 USA.
NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
Georgetown Univ, Med Ctr, Imaging Sci & Informat Syst Ctr, Washington, DC 20057 USA.
Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA.
Resources Future Inc, Ctr Dis Dynam Econ & Policy, Washington, DC USA.
Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA.
RP Hartley, DM (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, 2115 Wisconsin Ave NW,Suite 603, Washington, DC 20057 USA.
EM Hartley@isis.georgetown.edu
RI Niu, Tianchan/E-9771-2011;
OI Hartley, David/0000-0001-5202-6278; , David/0000-0003-2589-2538
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Centers for
Disease Control and Prevention [U01EH000418]; National Institutes of
Allergy and Infectious Diseases, National Institues of Health [R01
AI55607]
FX This study was supported by the Research and Policy for Infectious
Disease Dynamics program of the Science and Technology Directorate,
Department of Homeland Security and the Fogarty International Center,
National Institutes of Health. Christopher M. Barker and William K.
Reisen are supported, in part, by Centers for Disease Control and
Prevention grant U01EH000418 to study the impacts of climate change on
mosquitoborne virus transmission, and National Institutes of Allergy and
Infectious Diseases, National Institues of Health grant R01 AI55607 to
model amplification of WNV.
NR 72
TC 33
Z9 33
U1 4
U2 30
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD MAY
PY 2012
VL 86
IS 5
BP 884
EP 894
DI 10.4269/ajtmh.2012.11-0342
PG 11
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 935WY
UT WOS:000303554100027
PM 22556092
ER
PT J
AU Skare, O
Jugessur, A
Lie, RT
Wilcox, AJ
Murray, JC
Lunde, A
Nguyen, TT
Gjessing, HK
AF Skare, Oivind
Jugessur, Astanand
Lie, Rolv Terje
Wilcox, Allen James
Murray, Jeffrey Clark
Lunde, Astrid
Truc Trung Nguyen
Gjessing, Hakon Kristian
TI Application of a Novel Hybrid Study Design to Explore Gene-Environment
Interactions in Orofacial Clefts
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Birth defects; orofacial cleft; cleft lip; cleft palate; genetic
epidemiology
ID GENOME-WIDE ASSOCIATION; CASE-PARENT TRIADS; ORAL CLEFTS; EXPOSURE
INFORMATION; MATERNAL SMOKING; BIRTH-DEFECTS; PALATE; RISK; LIP;
CONSUMPTION
AB Orofacial clefts are common birth defects with strong evidence for both genetic and environmental causal factors. Candidate gene studies combined with exposures known to influence the outcome provide a highly targeted approach to detecting GxE interactions. We developed a new statistical approach that combines the case-control and offspring-parent triad designs into a hybrid design to search for GxE interactions among 334 autosomal cleft candidate genes and maternal first-trimester exposure to smoking, alcohol, coffee, folic acid supplements, dietary folate and vitamin A. The study population comprised 425 case-parent triads of isolated clefts and 562 control-parent triads derived from a nationwide study of orofacial clefts in Norway (19962001). A full maximum-likelihood model was used in combination with a Wald test statistic to screen for statistically significant GxE interaction between strata of exposed and unexposed mothers. In addition, we performed pathway-based analyses on 28 detoxification genes and 21 genes involved in folic acid metabolism. With the possible exception of the T-box 4 gene (TBX4) and dietary folate interaction in isolated CPO, there was little evidence overall of GxE interaction in our data. This study is the largest to date aimed at detecting interactions between orofacial clefts candidate genes and well-established risk exposures.
C1 [Skare, Oivind; Jugessur, Astanand; Gjessing, Hakon Kristian] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Skare, Oivind; Lie, Rolv Terje; Lunde, Astrid; Gjessing, Hakon Kristian] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Jugessur, Astanand] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Lie, Rolv Terje; Truc Trung Nguyen] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
[Wilcox, Allen James] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Murray, Jeffrey Clark] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Murray, Jeffrey Clark] Univ Iowa, Dept Epidemiol & Biol Sci, Iowa City, IA 52242 USA.
RP Skare, O (reprint author), Univ Oslo, Dept Biostat, Pb 1122 Blindern, N-0317 Oslo, Norway.
EM oivind.skare@medisin.uio.no
RI Gjessing, Hakon/A-5871-2012; Skare, Oivind/C-6330-2016;
OI Skare, Oivind/0000-0001-8043-2820; Wilcox, Allen/0000-0002-3376-1311
FU National Institutes of Health [DE08559, P60 DE13076, NIH P30 ES05605,
RO1 DE-11948-04]; Norwegian Research Council [NFR 177522/V50]; National
Institute of Environmental Health Sciences (NIH/NIEHS); National
Institutes of Health (NIH) [N01-HG-65403]
FX This research was supported by the National Institutes of Health
(DE08559, P60 DE13076, NIH P30 ES05605, and RO1 DE-11948-04), the
Norwegian Research Council (NFR 177522/V50) and in part by the
Intramural Research Program of the National Institute of Environmental
Health Sciences (NIH/NIEHS). We thank all participating families who
made this study possible, and Dr. Abee L. Boyles for her comments on an
earlier draft of this manuscript. Genotyping services were provided by
the Center for Inherited Disease Research (CIDR), which is fully funded
through a federal contract from the National Institutes of Health (NIH)
to The Johns Hopkins University, Contract Number N01-HG-65403. We thank
Ivy McMullen, Corinne Boehm, Kim Doheny and other CIDR staff involved in
this project. We also thank the US National Institute of Dental and
Craniofacial Research (NIDCR) for underwriting a significant proportion
of the genotyping costs by CIDR.
NR 55
TC 4
Z9 5
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD MAY
PY 2012
VL 76
BP 221
EP 236
DI 10.1111/j.1469-1809.2012.00707.x
PN 3
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 924NE
UT WOS:000302697800004
PM 22497478
ER
PT J
AU Brenner, M
Laragione, T
Shah, A
Mello, A
Remmers, EF
Wilder, RL
Gulko, PS
AF Brenner, Max
Laragione, Teresina
Shah, Anish
Mello, Adriana
Remmers, Elaine F.
Wilder, Ronald L.
Gulko, Percio S.
TI Identification of Two New Arthritis Severity Loci That Regulate Levels
of Autoantibodies, Interleukin-1 beta, and Joint Damage in Pristane- and
Collagen-Induced Arthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID EARLY RHEUMATOID-ARTHRITIS; QUANTITATIVE TRAIT LOCI; HISTOCOMPATIBILITY
COMPLEX; DISEASE SEVERITY; II COLLAGEN; SYNOVIAL FIBROBLASTS;
SUSCEPTIBILITY LOCI; RECEPTOR ANTAGONIST; PANNUS FORMATION; MAJOR
ARTHRITIS
AB Objective Cia3 is a locus on rat chromosome 4 that regulates severity and joint damage in collagen- and pristane-induced arthritis (CIA and PIA). This study was undertaken to refine the Cia3 genecontaining interval toward gene identification and obtain insights into its mode of action. Methods Five DA.F344(Cia3) subcongenic rat strains were generated and studied using the PIA and CIA models. Levels of antibodies against type II collagen (both allo- and autoantibodies) were measured. Joints and synovial tissue were collected 32 days after the induction of PIA (chronic stage) for histologic and quantitative polymerase chain reaction analysis of interleukin-1 beta (IL-1 beta) and matrix metalloproteinase (MMP) levels. Results Three subcongenic strains sharing the centromeric Cia3d interval were protected and 2 subcongenic strains sharing the telomeric Cia3g interval, which did not overlap with Cia3d, were also protected, developing significantly less severe CIA and PIA. Normal joint architecture was preserved in DA.F344(Cia3) and DA.F344(Cia3d) congenic rats with PIA, while DA rats had pronounced synovial hyperplasia, angiogenesis, inflammatory infiltration, and bone or cartilage erosions. The DA.F344(Cia3d) and DA.F344(Cia3g) strains had significantly lower synovial levels of IL-1 beta (5-fold and nearly 2-fold, respectively [the latter not reaching statistical significance]), MMP-1 (expressed predominantly in DA rats), MMP-3 (79-fold and 8-fold, respectively), and MMP-14 (21-fold and 1.4-fold, respectively) and reduced levels of pathogenic autoantibodies against type II collagen, compared with DA rats. Conclusion We have identified 2 new arthritis severity and articular damage loci within Cia3. These loci regulate pathogenic processes in 2 different models of rheumatoid arthritis, and the identification of these genes has the potential to generate new targets for therapies aimed at reducing disease severity and articular damage, and may additionally have prognostic value.
C1 [Gulko, Percio S.] Feinstein Inst Med Res, Lab Expt Rheumatol, Ctr Genom & Human Genet, Manhasset, NY 11030 USA.
[Wilder, Ronald L.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Gulko, Percio S.] Elmezzi Grad Sch Mol Med N Shore LIJ, Manhasset, NY USA.
RP Gulko, PS (reprint author), Feinstein Inst Med Res, Lab Expt Rheumatol, Ctr Genom & Human Genet, 350 Community Dr,Room 139, Manhasset, NY 11030 USA.
EM pgulko@nshs.edu
OI Brenner, Max/0000-0002-8010-148X
FU NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases) [R01-AR-46213]; NIH (National Institute of Allergy and
Infectious Diseases) [R01-AI-54348]
FX Supported by grants to Dr. Gulko from the NIH (National Institute of
Arthritis and Musculoskeletal and Skin Diseases grant R01-AR-46213 and
National Institute of Allergy and Infectious Diseases grant
R01-AI-54348).
NR 49
TC 5
Z9 5
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
EI 1529-0131
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAY
PY 2012
VL 64
IS 5
BP 1369
EP 1378
DI 10.1002/art.33468
PG 10
WC Rheumatology
SC Rheumatology
GA 931SG
UT WOS:000303239000011
PM 22076633
ER
PT J
AU Baird, K
Fry, TJ
Steinberg, SM
Bishop, MR
Fowler, DH
Delbrook, CP
Humphrey, JL
Rager, A
Richards, K
Wayne, AS
Mackall, CL
AF Baird, Kristin
Fry, Terry J.
Steinberg, Seth M.
Bishop, Michael R.
Fowler, Daniel H.
Delbrook, Cynthia P.
Humphrey, Jennifer L.
Rager, Alison
Richards, Kelly
Wayne, Alan S.
Mackall, Crystal L.
TI Reduced-Intensity Allogeneic Stem Cell Transplantation in Children and
Young Adults with Ultrahigh-Risk Pediatric Sarcomas
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Pediatric soft tissue sarcoma; Allogeneic stem cell transplantation;
Reduced-intensity transplantation; Solid tumor
ID BONE-MARROW-TRANSPLANTATION; METASTATIC SOLID TUMORS; TOTAL-BODY
IRRADIATION; SOFT-TISSUE SARCOMAS; VERSUS-HOST-DISEASE; EWINGS-SARCOMA;
PROGNOSTIC-FACTORS; EUROPEAN INTERGROUP; ADVANCED NEUROBLASTOMA;
CONSOLIDATION THERAPY
AB Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation. Biol Blood Marrow Transplant 18: 698-707 (2012) Published by Elsevier Inc on behalf of American Society for Blood and Marrow Transplantation
C1 [Baird, Kristin; Fry, Terry J.; Delbrook, Cynthia P.; Richards, Kelly; Wayne, Alan S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bishop, Michael R.; Fowler, Daniel H.] NCI, Expt Immunol & Transplantat Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Humphrey, Jennifer L.] Univ S Carolina, Sch Med, Columbia, SC USA.
[Rager, Alison] NIH, Clin Res Training Program, Bethesda, MD 20892 USA.
[Rager, Alison] Duke Univ, Sch Med, Durham, NC USA.
RP Baird, K (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1W-3940, Bethesda, MD 20892 USA.
EM kbaird@mail.nih.gov
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. The authors are employees of the United States
Government, and as such, this work was done in that capacity. The views
expressed do not necessarily represent the views of the National
Institutes of Health or the United States Government. The authors thank
Ronald E. Gress for his thoughtful insights. We also acknowledge the
exhaustive efforts of Natasha Brunson, Keith O'Neil, Leon Schnabel,
Joanne Derdak, Barbara Wise, our clinical fellows, and nursing staff.
Finally, we express sincere gratitude to our patients and their
families.
NR 55
TC 10
Z9 10
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 MAY
PY 2012
VL 18
IS 5
BP 698
EP 707
DI 10.1016/j.bbmt.2011.08.020
PG 10
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 935YQ
UT WOS:000303558500007
PM 21896345
ER
PT J
AU Moreno, C
Hasin, DS
Arango, C
Oquendo, MA
Vieta, E
Liu, SM
Grant, BF
Blanco, C
AF Moreno, Carmen
Hasin, Deborah S.
Arango, Celso
Oquendo, Maria A.
Vieta, Eduard
Liu, Shangmin
Grant, Bridget F.
Blanco, Carlos
TI Depression in bipolar disorder versus major depressive disorder: results
from the National Epidemiologic Survey on Alcohol and Related Conditions
SO BIPOLAR DISORDERS
LA English
DT Article
DE bipolar disorder; clinical classifications; depression; epidemiology
ID COMORBIDITY SURVEY REPLICATION; WEEKLY SYMPTOMATIC STATUS; TEST-RETEST
RELIABILITY; II DISORDER; UNIPOLAR DEPRESSION; CLINICAL-FEATURES;
NATURAL-HISTORY; DSM-V; INTERVIEW; PREVALENCE
AB Moreno C, Hasin DS, Arango C, Oquendo MA, Vieta E, Liu S, Grant BF, Blanco C. Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Bipolar Disord 2012: 14: 271282. (C) 2012 The Authors. Journal compilation (C) 2012 John Wiley & Sons A/S. Objectives: To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative face-to-face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Results: Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequentand number of depressive symptoms per MDE was higheramong subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Conclusions: Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications.
C1 [Moreno, Carmen; Arango, Celso] Hosp Gen Univ Gregorio Maranon, Dept Psiquiatria Nino & Adolescente, Ctr Invest Biomed Red Salud Mental, CIBERSAM, Madrid 28009, Spain.
[Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Hasin, Deborah S.; Oquendo, Maria A.; Liu, Shangmin; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA.
[Vieta, Eduard] Univ Barcelona, Bipolar Disorders Program, Inst Neurosci, Hosp Clin,IDIBAPS,CIBERSAM, Barcelona, Spain.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA.
RP Moreno, C (reprint author), Hosp Gen Univ Gregorio Maranon, Dept Psiquiatria Nino & Adolescente, Ctr Invest Biomed Red Salud Mental, CIBERSAM, Ibiza 43, Madrid 28009, Spain.
EM cmoreno@hggm.es
RI Vieta, Eduard/I-6330-2013; Blanco, Carlos/I-4906-2013; Arango Lopez,
Celso/H-6433-2015;
OI Vieta, Eduard/0000-0002-0548-0053; Blanco, Carlos/0000-0001-6187-3057;
Arango Lopez, Celso/0000-0003-3382-4754; Moreno,
Carmen/0000-0003-0541-4846
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); NIAAA,
National Institutes of Health (NIH); NIH [DA019606, DA020783, DA023200,
MH076051, R01AA08159, R01DA018652, K05AA00161, MH 57910, MH 62185];
Alicia Koplowitz Foundation; American Foundation for Suicide Prevention;
New York State Psychiatric Institute; CIBER de Salud Mental, Spanish
Ministry of Science and Innovation, Instituto de Salud Carlos III
[CIBER07/09, CIBERSAM]; Fundacion Alicia Koplowitz; Centro de
Investigacion Biomedica en Red de Salud Mental (CIBERSAM); AstraZeneca;
Bristol-Myers Squibb; Caja Navarra; Comunidad de Madrid; Fundacion Mutua
Madrilena; Instituto de Salud Carlos III; CIBERSAM; NARSAD; Spanish
Ministry of Education; Spanish Ministry of Science and Innovation;
Spanish Ministry of Health; Stanley Foundation; Eli Lilly Co; Janssen;
Almirall; European 7th Framework Program; GlaxoSmithKline;
Janssen-Cilag; Novartis; Organon; Otsuka; Pfizer; Sanofi-aventis; Seny
Foundation; Servier; Spanish Ministry of Health, the Spanish Ministry of
Science and Innovation (CIBERSAM); Stanley Medical Research Institute
FX The National Epidemiologic Survey on Alcohol and Related Conditions was
sponsored by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and funded, in part, by the Intramural Program, NIAAA, National
Institutes of Health (NIH). This study was supported by NIH grants
DA019606, DA020783, DA023200, and MH076051 (CB); R01AA08159,
R01DA018652, and K05AA00161 (DSH); MH 57910 and MH 62185 (MAO); the
Alicia Koplowitz Foundation (CM); the American Foundation for Suicide
Prevention (CB); the New York State Psychiatric Institute (CB, DSH,
MAO); and the CIBER de Salud Mental (CIBER07/09, CIBERSAM), Spanish
Ministry of Science and Innovation, Instituto de Salud Carlos III (CM,
CA, EV).; CM has received grant/research support from Fundacion Alicia
Koplowitz and Centro de Investigacion Biomedica en Red de Salud Mental
(CIBERSAM); and has served as a consultant for Bristol-Myers Squibb. CA
has received grant/research support from AstraZeneca, Bristol-Myers
Squibb, Caja Navarra, Comunidad de Madrid, Fundacion Alicia Koplowitz,
Fundacion Mutua Madrilena, Instituto de Salud Carlos III, CIBERSAM,
NARSAD, the Spanish Ministry of Education, the Spanish Ministry of
Science and Innovation, the Spanish Ministry of Health, and the Stanley
Foundation; and has served as a consultant for AstraZeneca,
Bristol-Myers Squibb, Foundation Alicia Koplowitz, Fundacion Marcelino
Botin, Janssen, Pfizer, Servier, the Spanish Ministry of Health, and the
Spanish Ministry of Science and Innovation. MAO has received
unrestricted educational grants from Eli Lilly & Co., AstraZeneca, and
Janssen. EV has received grant/research support from Almirall,
AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., the European 7th
Framework Program, GlaxoSmithKline, Janssen-Cilag, Novartis, Organon,
Otsuka, Pfizer, Sanofi-aventis, Seny Foundation, Servier, the Spanish
Ministry of Education, Social Policy and Sports, the Spanish Ministry of
Health, the Spanish Ministry of Science and Innovation (CIBERSAM), and
the Stanley Medical Research Institute; and has served as a consultant
for AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Forest Research
Institute, Geodon Richter, GlaxoSmithKline, Janssen, Jazz, Johnson &
Johnson, Lundbeck, MSD, Novartis, Organon, Otsuka, Pfizer,
Sanofi-Aventis, Servier, Takeda, and UBC. CB has received research
support from GlaxoSmithKline, Eli Lilly & Co., and Pfizer. DSH, SL, and
BFG report no financial relationships with commercial interests.
NR 50
TC 34
Z9 35
U1 1
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAY
PY 2012
VL 14
IS 3
BP 271
EP 282
DI 10.1111/j.1399-5618.2012.01009.x
PG 12
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 934IO
UT WOS:000303438000006
PM 22548900
ER
PT J
AU Little, MP
Rajaraman, P
Curtis, RE
Devesa, SS
Inskip, PD
Check, DP
Linet, MS
AF Little, M. P.
Rajaraman, P.
Curtis, R. E.
Devesa, S. S.
Inskip, P. D.
Check, D. P.
Linet, M. S.
TI Authors' reply to Kundi and Davis and colleagues
SO BRITISH MEDICAL JOURNAL
LA English
DT Letter
ID MOBILE; RISK
C1 [Little, M. P.; Rajaraman, P.; Curtis, R. E.; Devesa, S. S.; Inskip, P. D.; Check, D. P.; Linet, M. S.] NCI, Rockville, MD 20852 USA.
RP Little, MP (reprint author), NCI, Rockville, MD 20852 USA.
EM mark.little@nih.gov
RI Check, David/J-7184-2015
OI Check, David/0000-0003-3887-0493
NR 6
TC 0
Z9 0
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BRIT MED J
JI Br. Med. J.
PD MAY 1
PY 2012
VL 344
AR e3088
DI 10.1136/bmj.e3088
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 939MZ
UT WOS:000303816700026
ER
PT J
AU Freeman, LEB
DeRoos, AJ
Koutros, S
Blair, A
Ward, MH
Alavanja, M
Hoppin, JA
AF Freeman, Laura E. Beane
DeRoos, Anneclaire J.
Koutros, Stella
Blair, Aaron
Ward, Mary H.
Alavanja, Michael
Hoppin, Jane A.
TI Poultry and livestock exposure and cancer risk among farmers in the
agricultural health study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Livestock; Poultry; Cancer; Cohort study; Agriculture
ID NON-HODGKINS-LYMPHOMA; LUNG-CANCER; MULTIPLE-MYELOMA;
OCCUPATIONAL-EXPOSURE; PET BIRDS; AVIAN EXPOSURE; MORTALITY; OPERATIONS;
ENDOTOXIN; WORKERS
AB The purpose of this study is to evaluate cancer risk associated with raising animals as commodities, which is associated with a variety of exposures, such as infectious agents and endotoxins.
Information was available for 49,884 male farmers in the Agricultural Health Study, who reported livestock and poultry production at enrollment (1993-1997). Cancer incidence data were obtained through annual linkage to state registries. Using Poisson regression analyses, we evaluated whether the number and type of animals raised on the farm impacted cancer risk.
Overall, 31,848 (63.8%) male farmers reported raising any animals. Lung cancer risk decreased with increasing number of livestock on the farm (p trend = 0.04) and with raising poultry (Relative Risk (RR) = 0.6; 95% confidence interval (CI): 0.4-0.97). Raising poultry was associated with an increased risk of colon cancer (RR = 1.4; 95% CI: 0.99-2.0) with further increased with larger flocks (p trend = 0.02). Risk of non-Hodgkin lymphoma was also elevated in those who raised poultry (RR = 1.6; 95% CI: 1.0-2.4), but there was no evidence of increased risk with larger flocks (p trend = 0.5). Raising sheep was associated with a significantly increased risk of multiple myeloma (RR = 4.9; 95% CI: 2.4-12.0). Performing veterinary services increased the risk of Hodgkin lymphoma (RR = 12.2; 95% CI: 1.6-96.3).
We observed an inverse association between raising poultry and livestock and lung cancer risk and some evidence of increased risk of specific lymphohematopoietic malignancies with specific types of animals and performing veterinary services. Further research into associations between raising animals and cancer risk should focus on identification of etiologic agents.
C1 [Freeman, Laura E. Beane; Koutros, Stella; Blair, Aaron; Ward, Mary H.; Alavanja, Michael] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Freeman, Laura E. Beane; Koutros, Stella; Blair, Aaron; Ward, Mary H.; Alavanja, Michael; Hoppin, Jane A.] Dept Hlth & Human Serv, Bethesda, MD USA.
[DeRoos, Anneclaire J.] Univ Washington, Seattle, WA 98195 USA.
[DeRoos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
RP Freeman, LEB (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7240, Bethesda, MD 20892 USA.
EM freemala@mail.nih.gov
FU National Institutes of Health (National Cancer Institute) [Z01
CP010119]; National Institutes of Health (National Institute of
Environmental Health Sciences) [Z01 ES049030]
FX This work was supported by funds from the Intramural Research Program of
the National Institutes of Health (National Cancer Institute Z01
CP010119 and the National Institute of Environmental Health Sciences Z01
ES049030). All data used in these analyses were based on AHS data
release P1REL201005.00.
NR 32
TC 17
Z9 18
U1 0
U2 15
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 2012
VL 23
IS 5
BP 663
EP 670
DI 10.1007/s10552-012-9921-1
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 934CI
UT WOS:000303418200001
ER
PT J
AU Reding, KW
Chen, C
Lowe, K
Doody, DR
Carlson, CS
Chen, CT
Houck, J
Weiss, LK
Marchbanks, PA
Bernstein, L
Spirtas, R
McDonald, JA
Strom, BL
Burkman, RT
Simon, MS
Liff, JM
Daling, JR
Malone, KE
AF Reding, Kerryn W.
Chen, Chu
Lowe, Kimberly
Doody, David R.
Carlson, Christopher S.
Chen, Christina T.
Houck, John
Weiss, Linda K.
Marchbanks, Polly A.
Bernstein, Leslie
Spirtas, Robert
McDonald, Jill A.
Strom, Brian L.
Burkman, Ronald T.
Simon, Michael S.
Liff, Jonathan M.
Daling, Janet R.
Malone, Kathleen E.
TI Estrogen-related genes and their contribution to racial differences in
breast cancer risk
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Genetic variation; Racial disparities; Gene-environment
interactions; Hormone therapy
ID HORMONE-REPLACEMENT THERAPY; AFRICAN-AMERICAN WOMEN; MULTILOCUS GENOTYPE
DATA; POPULATION-STRUCTURE; RECEPTOR STATUS; REPRODUCTIVE EXPERIENCES;
TUMOR CHARACTERISTICS; METABOLISM GENOTYPES; ENDOGENOUS HORMONES;
MULTIETHNIC COHORT
AB Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p (het) = 0.003) and within CYP17A1 (rs743572; p (het) = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.
C1 [Reding, Kerryn W.; Chen, Chu; Doody, David R.; Carlson, Christopher S.; Chen, Christina T.; Houck, John; Daling, Janet R.; Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Reding, Kerryn W.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
[Chen, Chu; Carlson, Christopher S.; Malone, Kathleen E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Lowe, Kimberly] Exponent, Seattle, WA USA.
[Weiss, Linda K.] NCI, Canc Ctr Program, Rockville, MD USA.
[Marchbanks, Polly A.; McDonald, Jill A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Spirtas, Robert] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Burkman, Ronald T.] Baystate Hlth, Dept Obstet & Gynecol, Springfield, MA USA.
[Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Liff, Jonathan M.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Reding, KW (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Mail Stop M4-B874, Seattle, WA 98109 USA.
EM kreding@u.washington.edu
FU National Institute of Child Health and Human Development; National
Cancer Institute, through Emory University [N01 HD 3-3168]; Fred
Hutchinson Cancer Research Center [N01 HD 2-3166]; Karmanos Cancer
Institute at Wayne State University [N01 HD 3-3174]; University of
Pennsylvania [N01 HD-3-3176]; University of Southern California [N01 HD
3-3175]; Centers for Disease Control and Prevention [Y01 HD 7022];
National Cancer Institute [R03 CA 123584]; Cancer Epidemiology and
Biostatistics Training Grant [2 T32 CA 09168]; NINR [K99NR012232]
FX The authors would like to thank the study participants for their
contribution to this research. The CARE study was supported by the
National Institute of Child Health and Human Development, with
additional support from the National Cancer Institute, through contracts
with Emory University (N01 HD 3-3168), the Fred Hutchinson Cancer
Research Center (N01 HD 2-3166), Karmanos Cancer Institute at Wayne
State University (N01 HD 3-3174), the University of Pennsylvania (N01
HD-3-3176), and the University of Southern California (N01 HD 3-3175)
and through an intraagency agreement with the Centers for Disease
Control and Prevention (Y01 HD 7022). The research generating the AIMs
data was supported by the National Cancer Institute (R03 CA 123584). KWR
was supported by the Cancer Epidemiology and Biostatistics Training
Grant (2 T32 CA 09168) and NINR grant K99NR012232. The findings and
conclusions in this report are those of the authors and do not
necessarily represent the official position of the National Institutes
of Health or the Centers for Disease Control and Prevention. This
research was supported by funding from the National Institute of Child
Health and Human Development with additional support from the Centers
for Disease Control and Prevention and the National Cancer Institute.
NR 72
TC 18
Z9 19
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 2012
VL 23
IS 5
BP 671
EP 681
DI 10.1007/s10552-012-9925-x
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 934CI
UT WOS:000303418200002
PM 22418777
ER
PT J
AU Dubrow, R
Darefsky, AS
Freedman, ND
Hollenbeck, AR
Sinha, R
AF Dubrow, Robert
Darefsky, Amy S.
Freedman, Neal D.
Hollenbeck, Albert R.
Sinha, Rashmi
TI Coffee, tea, soda, and caffeine intake in relation to risk of adult
glioma in the NIH-AARP Diet and Health Study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Glioma; Brain neoplasms; Coffee; Tea; Soda; Caffeine
ID BRAIN-TUMORS; ONSET GLIOMA; CANCER; COHORT; GLIOBLASTOMA; CONSUMPTION;
DITERPENES; CALIFORNIA; NUTRITION; CAFESTOL
AB We utilized the large, prospective NIH-AARP Diet and Health Study to further explore the hypothesis, suggested by two recent prospective cohort studies, that increased intake of coffee, tea, soda, and/or caffeine is associated with reduced adult glioma risk.
At baseline in 1995-1996, dietary intake, including coffee, tea, and soda, was assessed with a food frequency questionnaire. We used Cox proportional hazards models to calculate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for glioma risk in relation to beverage intake.
During follow-up of 545,771 participants through 2006, 904 participants were diagnosed with glioma. We found no trends of decreasing glioma risk with increasing intake of specific beverages or total caffeine. HR patterns for consumption of the caffeinated versus decaffeinated form of each beverage were inconsistent with a specific caffeine effect. HR patterns of reduced glioma risk for most categories of beverage intake greater than "none" prompted a post hoc analysis that revealed borderline-significant inverse associations for any versus no intake of tea (HR = 0.84; 95 % CI, 0.69-1.03), total coffee plus tea (HR = 0.70; 95 % CI, 0.48-1.03), and soda (HR = 0.82; 95 % CI, 0.67-1.01).
The borderline-significant inverse associations could be explained by a threshold effect in which any beverage intake above a low level confers a beneficial effect, most likely due to beverage constituents other than caffeine. They could also be explained by non-drinkers of these beverages sharing unknown extraneous characteristics associated with increased glioma risk, or by chance.
C1 [Dubrow, Robert; Darefsky, Amy S.] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT 06520 USA.
[Freedman, Neal D.; Sinha, Rashmi] NCI NIH DHHS, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Dubrow, R (reprint author), Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT 06520 USA.
EM robert.dubrow@yale.edu
RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098
FU NIH, National Cancer Institute
FX Cancer incidence data from the Atlanta metropolitan area were collected
by the Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University. Cancer incidence data
from California were collected by the California Department of Health
Services, Cancer Surveillance Section. Cancer incidence data from the
Detroit metropolitan area were collected by the Michigan Cancer
Surveillance Program, Community Health Administration, State of
Michigan. The Florida cancer incidence data used in this report were
collected by the Florida Cancer Data System 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, Division of
Public Health Services, Arizona Department of Health Services. Cancer
incidence data from Texas were collected by the Texas Cancer Registry,
Cancer Epidemiology and Surveillance Branch, Texas Department of State
Health Services. Cancer incidence data from Nevada were collected by the
Nevada Central Cancer Registry, Center for Health Data and Research,
Bureau of Health Planning and Statistics, State Health Division, State
of Nevada Department of Health and Human Services. We are indebted to
the participants in the NIH-AARP Diet and Health Study for their
outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace
Morrissey from Westat for study outcomes ascertainment and management
and Leslie Carroll and Jane Wang at Information Management Services for
data support and analysis. This research was supported [in part] by the
Intramural Research Program of the NIH, National Cancer Institute.
NR 27
TC 7
Z9 8
U1 0
U2 20
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 2012
VL 23
IS 5
BP 757
EP 768
DI 10.1007/s10552-012-9945-6
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 934CI
UT WOS:000303418200011
PM 22457000
ER
PT J
AU Faupel-Badger, JM
Wang, YP
Staff, AC
Karumanchi, SA
Stanczyk, FZ
Pollak, M
Hoover, RN
Troisi, R
AF Faupel-Badger, Jessica M.
Wang, Yuping
Staff, Anne Cathrine
Karumanchi, S. Ananth
Stanczyk, Frank Z.
Pollak, Michael
Hoover, Robert N.
Troisi, Rebecca
TI Maternal and cord steroid sex hormones, angiogenic factors, and
insulin-like growth factor axis in African-American preeclamptic and
uncomplicated pregnancies
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Preeclampsia; African-American; sFlt-1; IGF; Leptin; Prolactin
ID BREAST-CANCER RISK; FOR-GESTATIONAL-AGE; ANTIANGIOGENIC FACTORS; SOLUBLE
ENDOGLIN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; TYROSINE KINASE-1;
NULLIPAROUS WOMEN; PATHOGENESIS; ESTROGEN
AB A history of a preeclamptic pregnancy has been associated with subsequent increased risk of cardiovascular disease in the mother and decreased risk of breast cancer in both the mother and offspring. The concentrations of steroid sex hormones, angiogenic factors, and other proteins during pregnancy are important components of the in utero environment and may mediate the association of preeclampsia with later health outcomes. This study sought to compare an extensive profile of biological markers in both maternal and umbilical cord samples in preeclamptic and uncomplicated pregnancies of a predominantly African-American population.
Steroid sex hormones, angiogenic factors, and components of the insulin-like growth factor axis were measured in maternal and umbilical cord sera from 48 pregnancies complicated by preeclampsia and 43 uncomplicated pregnancies. Regression models estimated the associations of these markers with preeclampsia, after adjusting for maternal and gestational age.
Concentrations of androgens (testosterone p = 0.06 and androstenedione p = 0.08) and the anti-angiogenic factors soluble fms-like kinase 1 (p = 0.004) and soluble endoglin (p = 0.004) were higher in the maternal circulation of women diagnosed with preeclampsia. These findings also were noted when the analyses were restricted to only African-American participants (77% of overall study population). Furthermore, among African-Americans, cord insulin-like growth factor-1 was lower in preeclamptic pregnancies than in controls.
The associations of maternal androgens and anti-angiogenic factors with preeclampsia are consistent with prior reports from predominantly Caucasian populations. Alterations in these analytes as well as other maternal and fetal biomarkers in preeclampsia could mediate the associations of preeclampsia with later health consequences.
C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Bethesda, MD 20892 USA.
[Faupel-Badger, Jessica M.; Hoover, Robert N.; Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wang, Yuping] Louisiana State Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, Shreveport, LA 71105 USA.
[Staff, Anne Cathrine] Oslo Univ Hosp, Dept Obstet & Gynaecol, Ulleval, Norway.
[Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway.
[Karumanchi, S. Ananth] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada.
RP Faupel-Badger, JM (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, 6120 Execut Blvd EPS,Suite 150E,MSC 7105, Bethesda, MD 20892 USA.
EM badgerje@mail.nih.gov
RI Pollak, Michael/G-9094-2011
OI Pollak, Michael/0000-0003-3047-0604
FU National Cancer Institute (NCI), National Institutes of Health; Center
for Cancer Training, NCI
FX We would like to thank Lisa Philibert, RN and Kimberly Mandino, RN at
LSUHSC-Shreveport for patient recruitment and clinical data collection
for the study. We also thank Marianne Hyer and David Castenson at
Information Management Systems for their contributions to data
verification and analysis and Dr. Jun Zhang at NICHD for collaborating
with us on the parent study. This research was supported in part by the
intramural research program of the National Cancer Institute (NCI),
National Institutes of Health and the Center for Cancer Training, Cancer
Prevention Fellowship Program, NCI.
NR 40
TC 8
Z9 8
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 2012
VL 23
IS 5
BP 779
EP 784
DI 10.1007/s10552-012-9934-9
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 934CI
UT WOS:000303418200013
PM 22418778
ER
PT J
AU Kapetanovic, IM
Muzzio, M
McCormick, DL
Thompson, TN
Johnson, WD
Horn, TL
Mohammed, A
Rao, CV
Kopelovich, L
AF Kapetanovic, Izet M.
Muzzio, Miguel
McCormick, David L.
Thompson, Thomas N.
Johnson, William D.
Horn, Thomas L.
Mohammed, Altaf
Rao, Chinthalapally V.
Kopelovich, Levy
TI Pharmacokinetics and tissue and tumor exposure of CP-31398, a
p53-stabilizing agent, in rats
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE p53; Chemoprevention; Pharmacokinetics; Liver; Colon tumor; Rat
ID MUTANT P53; CANCER; RESTORATION; SUPPRESSION; THERAPY; MICE
AB CP-31398 (N'-[2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazolin-4-yl]-N,N-dimethylpropane-1,3-diamine hydrochloride) is one of the new class of agents that can stabilize the DNA-binding domain of p53 and thereby maintain the activity of p53 as a tumor suppressor and transcription factor. Through its activity as a p53 stabilizer, CP-31398 demonstrates significant cancer preventive and therapeutic activity in several in vivo animal models. The objective of the current study was to describe the pharmacokinetic profile and tissue distribution of this novel agent following intravenous or oral (gavage and dietary) administration.
CP-31398 was administered to male CD and F344 rats as a single intravenous bolus dose or by daily oral gavage dosing. Male F344 rats also received drug as an ad libitum dietary supplement. Plasma, liver, skin, colon, and colon tumor samples were collected after oral dosing. Concentrations of CP-31398 in plasma and tissue samples were analyzed using LC-MS/MS, and the resultant data were subjected to a non-compartmental pharmacokinetic analysis.
Bioavailability (12-32%), elimination half-life (14-20 h), clearance (4.2-4.8 l/h/kg), and volume of distribution (70-82 l/kg) were determined. Tissue levels of CP-31398 after oral (gavage or diet) administration were several orders of magnitude higher than were corresponding plasma concentrations; CP-31398 levels were especially high in colon and liver. Levels of CP-31398 in tissues were higher after gavage dosing than after dietary administration.
CP-31398 is bioavailable and has a relatively long elimination half-life, which supports the achievement of plasma steady-state levels with a once daily dosing regimen. CP-31398 exhibits a dramatically high volume of distribution, which is consistent with its tissue concentrations being much higher than corresponding plasma levels. It is accumulated in colon tumor tissues, albeit at lower concentrations than found in liver, skin, and colon.
C1 [Kapetanovic, Izet M.; Kopelovich, Levy] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Muzzio, Miguel; McCormick, David L.; Johnson, William D.; Horn, Thomas L.] IIT Res Inst, Life Sci Grp, Chicago, IL 60616 USA.
[Mohammed, Altaf; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Chemoprevent & Drug Dev, Oklahoma City, OK 73104 USA.
[Thompson, Thomas N.] R&D Serv Pharma Consulting, Omaha, NE 68154 USA.
RP Kapetanovic, IM (reprint author), NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, 6130 Executive Blvd,Rm 2116, Bethesda, MD 20892 USA.
EM kapetani@mail.nih.gov
FU National Cancer Institute, Department of Health and Human Services
[N01-CN-43304]
FX These studies were supported by contract number N01-CN-43304 from the
National Cancer Institute, Department of Health and Human Services.
NR 19
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD MAY
PY 2012
VL 69
IS 5
BP 1301
EP 1306
DI 10.1007/s00280-011-1811-9
PG 6
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 934CK
UT WOS:000303418500021
PM 22302406
ER
PT J
AU Yewdell, JW
Brooke, CB
AF Yewdell, Jonathan W.
Brooke, Christopher B.
TI Monocytes, viruses and metaphors Hanging the Trojan horse
SO CELL CYCLE
LA English
DT Editorial Material
ID CELLS
C1 [Yewdell, Jonathan W.; Brooke, Christopher B.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
FU Intramural NIH HHS
NR 7
TC 0
Z9 0
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAY 1
PY 2012
VL 11
IS 9
BP 1748
EP 1749
DI 10.4161/cc.20311
PG 2
WC Cell Biology
SC Cell Biology
GA 935OL
UT WOS:000303528500011
PM 22517432
ER
PT J
AU Yamane, H
Paul, WE
AF Yamane, Hidehiro
Paul, William E.
TI Memory CD4(+) T Cells: fate determination, positive feedback and
plasticity
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE T helper cell differentiation; Effector CD4(+) T cells; Memory CD4(+) T
cells; T cell plasticity; T helper lineage-specific transcription
factors; Positive feedback regulation by cytokines
ID TRANSCRIPTION FACTOR GATA-3; INTERFERON-GAMMA; IN-VIVO; PRODUCE
INTERLEUKIN-4; TH2 DIFFERENTIATION; HELPER-CELLS; IFN-GAMMA; EXPRESSION;
IL-4; RESPONSES
AB Na < ve CD4(+) T cells undergo massive cell proliferation upon encountering their cognate ligand. This proliferation depends upon appropriate cues from the antigen-presenting cells that have processed the antigen and present the peptide to the T cells, and requires the establishment of a cytokine environment that can support such proliferation. Expansion of antigen-specific CD4(+) T cells needs to be coupled with differentiation into one of several effector/regulatory phenotypes if the priming event is to result in cells that can initially act to control the particular pathogen that elicited the response, and later to serve as memory cells to insure an appropriate response upon reintroduction of the pathogen. Here, we discuss the initiation of T helper lineage commitment, the positive feedback regulation by the cytokine environment to enhance and stabilize the differentiation into distinct T helper subsets, and the biological significance of CD4(+) T cell plasticity and long-term CD4(+) T cell memory.
C1 [Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Yamane, H (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hyamane@niaid.nih.gov; wpaul@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX The work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA. We thank Dr. Ryoji Yagi for critical reading of the
manuscript.
NR 59
TC 15
Z9 16
U1 1
U2 14
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAY
PY 2012
VL 69
IS 10
BP 1577
EP 1583
DI 10.1007/s00018-012-0966-9
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 935HN
UT WOS:000303509800003
PM 22481436
ER
PT J
AU Hoffman, HJ
Dobie, RA
Ko, CW
Themann, CL
Murphy, WJ
AF Hoffman, Howard J.
Dobie, Robert A.
Ko, Chia-Wen
Themann, Christa L.
Murphy, William J.
TI Hearing Threshold Levels at Age 70 Years (65-74 Years) in the Unscreened
Older Adult Population of the United States, 1959-1962 and 1999-2006
SO EAR AND HEARING
LA English
DT Article
AB Objectives: To provide hearing threshold percentiles from unscreened older adults for creating new Annex B reference standards.
Design: Percentiles are calculated, and 95% confidence intervals for medians from two U. S. surveys are compared graphically.
Results: Median thresholds are lower (better) in the 1999-2006 National Health and Nutrition Examination Survey for men across all frequencies except 1 kHz. Results for women are similar; however, there is more overlap in confidence intervals across frequencies.
Conclusions: The prevalence of hearing impairment in older adults, age 70 years (65-74 years), is lower in 1999-2006 compared with 19591962, consistent with our earlier findings for younger adults.
C1 [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD 20892 USA.
[Dobie, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Otolaryngol Head & Neck Surg, San Antonio, TX 78229 USA.
[Ko, Chia-Wen] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Themann, Christa L.; Murphy, William J.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
RP Hoffman, HJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Suite 400A,Execut Plaza S Bldg,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM hoffmanh@nidcd.nih.gov
OI dobie, robert/0000-0003-3833-1772
FU National Institute on Deafness and Other Communication Disorders;
National Institute for Occupational Safety and Health
FX The National Health and Nutrition Examination Survey 1999-2006
audiometric data collection was funded with National Institute on
Deafness and Other Communication Disorders research contract funds via
an Interagency Agreement between the National Institute on Deafness and
Other Communication Disorders and the National Center for Health
Statistics. The National Institute for Occupational Safety and Health
provided funding for the audiometric testing equipment, training and
monitoring of technicians, and editing of preliminary data files. The
National Institute for Occupational Safety and Healt collaboration was
funded and managed via Interagency Agreements with the National
Institute on Deafness and Other Communication Disorders and the National
Center for Health Statistics. Audiometric testing was conducted in the
field by health technicians employed by Westat, Inc., under contract
with the National Center for Health Statistics.
NR 15
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
J9 EAR HEARING
JI Ear Hear.
PD MAY-JUN
PY 2012
VL 33
IS 3
BP 437
EP 440
DI 10.1097/AUD.0b013e3182362790
PG 4
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 934OT
UT WOS:000303454400013
PM 22080933
ER
PT J
AU Oh, JY
Choi, H
Lee, RH
Roddy, GW
Ylostalo, JH
Wawrousek, E
Prockop, DJ
AF Oh, Joo Youn
Choi, Hosoon
Lee, Ryang Hwa
Roddy, Gavin W.
Yloestalo, Joni H.
Wawrousek, Eric
Prockop, Darwin J.
TI Identification of the HSPB4/TLR2/NF-?B axis in macrophage as a
therapeutic target for sterile inflammation of the cornea
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE cornea; HSPB4; inflammation; macrophage; toll-like receptor 2
ID ALPHA-A-CRYSTALLIN; HEAT-SHOCK-PROTEIN; OXIDATIVE STRESS; CELLS;
SECRETONEURIN; RETINA; EYE; NEUROPEPTIDE; MECHANISMS; EXPRESSION
AB Sterile inflammation underlies many diseases of the cornea including serious chemical burns and the common dry eye syndrome. In search for therapeutic targets for corneal inflammation, we defined the kinetics of neutrophil infiltration in a model of sterile injury to the cornea and identified molecular and cellular mechanisms triggering inflammatory responses. Neutrophil infiltration occurred in two phases: a small initial phase (Phase I) that began within 15?min after injury, and a larger second phase (Phase II) that peaked at 2448?h. Temporal analysis suggested that the neuropeptide secretoneurin initiated Phase I without involvement of resident macrophages. Phase II was initiated by the small heat shock protein HSPB4 that was released from injured keratocytes and that activated resident macrophages via the TLR2/NF-?B pathway. The Phase II inflammation was responsible for vision-threatening opacity and was markedly suppressed by different means of inhibition of the HSPB4/TLR2/NF-?B axis: in mice lacking HSPB4 or TLR2, by antibodies to HSPB4 or by TNF-a stimulated gene/protein 6 that CD44-dependently inhibits the TLR2/NF-?B pathway. Therefore, our data identified the HSPB4/TLR2/NF-?B axis in macrophages as an effective target for therapy of corneal inflammation.
C1 [Oh, Joo Youn; Choi, Hosoon; Lee, Ryang Hwa; Roddy, Gavin W.; Yloestalo, Joni H.; Prockop, Darwin J.] Scott & White Mem Hosp & Clin, Coll Med, Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Temple, TX 76508 USA.
[Wawrousek, Eric] NEI, NIH, Bethesda, MD 20892 USA.
RP Prockop, DJ (reprint author), Scott & White Mem Hosp & Clin, Coll Med, Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Temple, TX 76508 USA.
EM prockop@medicine.tamhsc.edu
FU NIH [R21EY020962]
FX This study was supported in part by NIH grant R21EY020962. We gratefully
acknowledge help from Laura Quinlivan for assistance in animal
experiments.
NR 44
TC 16
Z9 16
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD MAY
PY 2012
VL 4
IS 5
BP 435
EP 448
DI 10.1002/emmm.201200221
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 935DK
UT WOS:000303498900009
PM 22359280
ER
PT J
AU Zannad, F
Stough, WG
Pocock, SJ
Sleight, P
Cushman, WC
Cleland, JG
McMurray, JJ
Lonn, E
Geller, NL
Wedel, H
Abadie, E
Alonso-Garcia, A
Pitt, B
AF Zannad, Faiez
Stough, Wendy Gattis
Pocock, Stuart J.
Sleight, Peter
Cushman, William C.
Cleland, John G. F.
McMurray, John J. V.
Lonn, Eva
Geller, Nancy L.
Wedel, Hans
Abadie, Eric
Alonso-Garcia, Angeles
Pitt, Bertram
TI Diabetes clinical trials: helped or hindered by the current shift in
regulatory requirements?
SO EUROPEAN HEART JOURNAL
LA English
DT Review
DE Diabetes mellitus; Cardiovascular disease; Clinical trials
ID AMERICAN-HEART-ASSOCIATION; INTENSIVE GLYCEMIC CONTROL; BLOOD-GLUCOSE
CONTROL; RANDOMIZED CONTROLLED-TRIALS; LONG-TERM COMPLICATIONS;
ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION;
THIAZOLIDINEDIONE THERAPY; VASCULAR COMPLICATIONS
AB Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs.
C1 [Zannad, Faiez] Nancy Univ, Hop Jeanne dArc, INSERM, Ctr Invest Clin 9501, F-54200 Nancy, France.
[Zannad, Faiez] Nancy Univ, Hop Jeanne dArc, Ctr Hosp Univ, Unite 961, F-54200 Nancy, France.
[Zannad, Faiez] Nancy Univ, Hop Jeanne dArc, Dept Cardiol, F-54200 Nancy, France.
[Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA.
[Pocock, Stuart J.] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England.
[Sleight, Peter] Univ Oxford, Nuffield Dept Med, Oxford OX3 9DU, England.
[Cushman, William C.] Univ Tennessee, Coll Med, Vet Affairs Med Ctr, Memphis, TN USA.
[Cleland, John G. F.] Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England.
[McMurray, John J. V.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland.
[McMurray, John J. V.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Lonn, Eva] McMaster Univ, Div Cardiol, Dept Med, Populat Hlth Res Inst, Hamilton, ON L8S 4L8, Canada.
[Geller, Nancy L.] NHLBI, Bethesda, MD 20892 USA.
[Wedel, Hans] Nord Sch Publ Hlth, Gothenburg, Sweden.
[Abadie, Eric] French Agcy Safety Hlth Prod AFSSAPS, Paris, France.
[Alonso-Garcia, Angeles] Sci Advice Working Party European Med Agcy, Madrid, Spain.
[Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA.
RP Zannad, F (reprint author), Nancy Univ, Hop Jeanne dArc, INSERM, Ctr Invest Clin 9501, F-54200 Nancy, France.
EM f.zannad@chu-nancy.fr
RI Stough, Wendy/R-4287-2016;
OI Stough, Wendy/0000-0001-8290-1205; Cleland, John/0000-0002-1471-7016;
mcmurray, john/0000-0002-6317-3975
FU Association de Recherche et d'Information en Cardiologie (ARISC) a
non-profit educational organization, in Nancy, France; Novartis; GSK;
Merck; FP7
FX This paper was generated from discussions during the 7th Global
Cardiovascular Clinical Trialists (CVCT) Forum held in Paris, France, in
December 2010. CVCT was organized by the Clinical Investigation Center
(CIC) Inserm, CHU, and University Henri Poincare of Nancy, France and
funded by an unrestricted educational grant from Association de
Recherche et d'Information en Cardiologie (ARISC) a non-profit
educational organization, in Nancy, France. ARISC had no involvement in
preparation, review, or approval of the manuscript for publication.; All
authors received travel expense reimbursement to attend the CVCT meeting
from INSERM, Centre d'Investigation Clinique, Centre Hospitalier
Universitaire, Nancy, France. Faiez Zannad: Pfizer, Inc. (Steering
Committee). W.G.S.: INSERM, Centre d'Investigation Clinique, Centre
Hospitalier Universitaire, Nancy, France (travel expense reimbursement
to attend CVCT 2010; professional/project management/administrative time
related to preparation of this paper). W.C.C.: Consultant to Takeda,
Novartis, Merck, Sanofi-Aventis, BMS, Gilead, Daiichi-Sankyo,
Theravance, and Noven; active or pending grants from Novartis, GSK, and
Merck. J.G.F.C.: Active or pending grant from FP7. H.W.: Roche (Steering
Committee member). B. P.: Consultant for Pfizer, Merck, Novartis,
Takeda, Astra Zeneca, Bayer.
NR 61
TC 12
Z9 12
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD MAY
PY 2012
VL 33
IS 9
BP 1049
EP U29
DI 10.1093/eurheartj/ehr437
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 937JD
UT WOS:000303653900011
PM 22422830
ER
PT J
AU Jann, MW
Spratlin, V
Momary, K
Zhang, HL
Turner, D
Penzak, SR
Wright, A
VanDenBerg, C
AF Jann, Michael W.
Spratlin, Vicky
Momary, Kathryn
Zhang, Hailing
Turner, David
Penzak, Scott R.
Wright, Alan
VanDenBerg, Chad
TI Lack of a pharmacokinetic drug-drug interaction with venlafaxine
extended-release/indinavir and desvenlafaxine extended-release/indinavir
SO EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE Drug interaction; Venlafaxine XR; Desvenlafaxine XR; Indinavir;
P-glycoprotein
ID P-GLYCOPROTEIN; GRAPEFRUIT JUICE; HIV-INFECTION; IN-VITRO; INDINAVIR;
METABOLITES; ABSORPTION; INHIBITORS; BARRIER; CYP2D6
AB To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers.
This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 +/- 8.0 years).
Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software.
Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects.
No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.
C1 [Jann, Michael W.; Spratlin, Vicky; Momary, Kathryn; Zhang, Hailing; Turner, David; Wright, Alan; VanDenBerg, Chad] Mercer Univ, Coll Pharm & Hlth Sci, Atlanta, GA 30341 USA.
[Penzak, Scott R.] NIH, Clin Pharmacokinet Lab, Bethesda, MD 20892 USA.
RP Jann, MW (reprint author), Mercer Univ, Coll Pharm & Hlth Sci, 3001 Mercer Univ Dr, Atlanta, GA 30341 USA.
EM jann_mw@mercer.edu
FU Pfizer, Inc.; Pfizer; Janssen Pharmaceuticals; Johnson/Johnson; Eli
Lilly; Coca Cola Company
FX This study was supported by Pfizer, Inc. through the
investigator-initiated research study program. Dr. Jann has received
research grants from Pfizer and Janssen Pharmaceuticals. Drs. Spratlin
and VanDenBerg have received research grants from Pfizer,
Johnson/Johnson, Eli Lilly, and the Coca Cola Company. Dr. Momary has
received research funding from Pfizer. Dr. Zhang, Dr. Penzak, Dr.
Wright, and Mr. Turner have nothing to disclose.
NR 26
TC 2
Z9 4
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0031-6970
J9 EUR J CLIN PHARMACOL
JI Eur. J. Clin. Pharmacol.
PD MAY
PY 2012
VL 68
IS 5
BP 715
EP 721
DI 10.1007/s00228-011-1180-7
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 934OD
UT WOS:000303452800028
PM 22173281
ER
PT J
AU Feifel, D
Shilling, PD
Belcher, AM
AF Feifel, David
Shilling, Paul D.
Belcher, Annabelle M.
TI The effects of oxytocin and its analog, carbetocin, on genetic deficits
in sensorimotor gating
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Schizophrenia; Antipsychotics; Prepulse inhibition; Brown-Norway; Animal
models
ID PREPULSE INHIBITION; SCHIZOPHRENIC-PATIENTS; CEREBROSPINAL-FLUID; RAT
STRAIN; BEHAVIOR; VASOPRESSIN; AUTISM; BRAIN; MODEL
AB Converging evidence from preclinical and clinical studies suggest that oxytocin has therapeutic potential for schizophrenia and other neuropsychiatric disorders. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating, an important brain function involved in filtering environmental information. We previously demonstrated that systemically administered oxytocin reversed psychostimulant-induced PPI deficits in rats suggesting that oxytocin can produce antipsychotic-like central effects. That finding was supported by a recent trial in humans, which found that intranasal oxytocin reduced symptoms of schizophrenia. The goal of this study was to extend this line of investigation by testing the effects of oxytocin, and a structural analog of oxytocin, carbetocin, on non-pharmacological deficits in PPI. In experiment 1, Brown Norway (BN) rats, a rat strain that has naturally low PPI, were given either saline or one of three doses of oxytocin (0.04-1.0 mg/kg, sc). In experiment 2, BN rats were given either saline, one of three doses of carbetocin (0.04-1.0 mg/kg) or oxytocin (1 mg/kg). PPI and acoustic startle response (ASR) of rats were tested. Oxytocin significantly increased PPI (P<0.01) and decreased ASR levels (P<0.01) in BN rats in a dose-dependent fashion. In contrast, carbetocin had no effect on PPI levels or ASR. The facilitation of BN PPI by oxytocin is similar to what we have previously observed with clozapine and thus further supports oxytocin having antipsychotic properties. In contrast to oxytocin, our data do not support the use of carbetocin as an antipsychotic drug. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.
C1 [Feifel, David; Shilling, Paul D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Belcher, Annabelle M.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Feifel, D (reprint author), Univ Calif San Diego, Dept Psychiat, 200 W Arbor Dr, San Diego, CA 92103 USA.
EM dfeifel@ucsd.edu
FU NIHM [R01MH080910-01A2]; Abbott Labs; Astra Zeneca; Bristol Myers
Squibb; Eli Lilly; Forest; Jansen; Merck; Otsuka; Pfizer; Sanofi;
Shinogi; Shire; Sunovion
FX Funding for this study was provided by NIHM Grant R01MH080910-01A2; the
NIMH had no further rote in study design; in the collection, analysis
and interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication.; In the past three years,
Dr. Feifel has received funds in return for one or more of the
following: conducting contracted research, conducting
investigator-initiated research, advisory board participation, and
speaking from the following pharmaceutical companies: Abbott Labs, Astra
Zeneca, Bristol Myers Squibb, Eli Lilly, Forest, Jansen, Merck, Otsuka,
Pfizer, Sanofi, Shinogi, Shire, and Sunovion. Dr. Feifel has no conflict
of interest. Dr. Belcher and Dr. Shilling declare that, except for
income received from their respective primary employers, no financial
support or compensation has been received from any individual or
corporate entity over the past three years for research or professional
service and there are no personal financial holdings that could be
perceived as constituting a potential conflict of interest.
NR 27
TC 18
Z9 21
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAY
PY 2012
VL 22
IS 5
BP 374
EP 378
DI 10.1016/j.euroneuro.2011.09.004
PG 5
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 935WJ
UT WOS:000303552600007
PM 21962914
ER
PT J
AU Plenz, D
AF Plenz, D.
TI Neuronal avalanches and coherence potentials
SO EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS
LA English
DT Article
ID SELF-ORGANIZED CRITICALITY; FOREST-FIRE MODEL; CORTICAL ACTIVITY;
SYNCHRONOUS SPIKING; NEURAL-NETWORKS; IN-VIVO; STIMULUS PROPERTIES;
CELLULAR-AUTOMATA; CROSS-CORRELATION; CEREBRAL-CORTEX
AB The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.
C1 NIMH, Sect Crit Brain Dynam, NIH, Rockville, MD 20852 USA.
RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, NIH, Rockville, MD 20852 USA.
EM plenzd@mail.nih.gov
FU National Institute of Mental Health, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, NIH. I thank Dr. Thiagarajan for
the branching parameter analysis in vivo and members of my group for
helpful discussions and critical reading of earlier versions of the
manuscript.
NR 147
TC 29
Z9 29
U1 2
U2 15
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1951-6355
EI 1951-6401
J9 EUR PHYS J-SPEC TOP
JI Eur. Phys. J.-Spec. Top.
PD MAY
PY 2012
VL 205
IS 1
BP 259
EP 301
DI 10.1140/epjst/e2012-01575-5
PG 43
WC Physics, Multidisciplinary
SC Physics
GA 933CU
UT WOS:000303337700017
ER
PT J
AU Lowell, SY
Reynolds, RC
Chen, G
Horwitz, B
Ludlow, CL
AF Lowell, Soren Y.
Reynolds, Richard C.
Chen, Gang
Horwitz, Barry
Ludlow, Christy L.
TI Functional connectivity and laterality of the motor and sensory
components in the volitional swallowing network
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE Swallowing; Neuroimaging; Functional connectivity; Correlations; fMRI
ID CEREBRAL CORTICAL REPRESENTATION; HUMAN PARIETAL OPERCULUM;
OROPHARYNGEAL DYSPHAGIA; CORTEX; STROKE; BRAIN; STIMULATION; ACTIVATION;
ADULTS; HUMANS
AB Functional neuroimaging has shown that multiple brain regions are active during volitional swallowing. Little is known, however, about which regions integrate motor execution and sensory feedback in the swallowing system. Although unilateral brain lesions in either hemisphere can produce swallowing deficits, some functional neuroimaging studies indicate that the left hemisphere has greater activation in certain sensory and motor-related swallowing regions. In this study, correlation coefficients were computed for five seed regions during volitional saliva swallowing to determine the functional relationships of these regions with the rest of the brain: the anterior and posterior insula, inferior frontal gyrus (BA44), primary sensory cortex (S1), and primary motor cortex (M1). A laterality index (LI) was derived that accounts for relative differences in total, positive connected voxels for the left/right hemisphere seeds. Clusters of significantly connected voxels were greater from the anterior and posterior insula than from the other three seed regions. Interactions of the insula with other brain regions were greater on the left than on the right during volitional swallowing. Group means showed laterality in the anterior insula (LI = 0.25) and the posterior insula (LI = 0.33). BA44 showed a lesser degree of difference in left versus right hemisphere interactions (LI = 0.12) while S1 did not show lateralization (LI = 0.02) and M1 showed some predominance of interactions in the right hemisphere (LI = -0.19). The greater connectivity from the left hemisphere insula to brain regions within and across hemispheres suggests that the insula is a primary integrative region for volitional swallowing in humans.
C1 [Lowell, Soren Y.] Syracuse Univ, Dept Commun Sci & Disorders, Syracuse, NY 13210 USA.
[Lowell, Soren Y.; Ludlow, Christy L.] Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA.
[Reynolds, Richard C.; Chen, Gang] NIMH, NIH, Bethesda, MD 20892 USA.
[Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA.
RP Lowell, SY (reprint author), Syracuse Univ, Dept Commun Sci & Disorders, 805 S Crouse Ave, Syracuse, NY 13210 USA.
EM slowell@syr.edu
OI Ludlow, Christy/0000-0002-2015-6171
FU Divisions of Intramural Research of the National Institute of
Neurological Disorders and Stroke; National Institute on Deafness and
Other Communication Disorders
FX We thank Adam Gerson for his assistance on initial methods for this
study. This research was supported by the Divisions of Intramural
Research of the National Institute of Neurological Disorders and Stroke
and of the National Institute on Deafness and Other Communication
Disorders.
NR 64
TC 20
Z9 25
U1 0
U2 7
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 MAY
PY 2012
VL 219
IS 1
BP 85
EP 96
DI 10.1007/s00221-012-3069-9
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 934VP
UT WOS:000303475100008
PM 22441258
ER
PT J
AU Yan, XX
Cai, Y
Zhang, XM
Luo, XG
Cai, HB
Rose, GM
Patrylo, PR
AF Yan, Xiao-Xin
Cai, Yan
Zhang, Xue-Mei
Luo, Xue-Gang
Cai, Huaibin
Rose, Gregory M.
Patrylo, Peter R.
TI BACE1 elevation is associated with aberrant limbic axonal sprouting in
epileptic CD1 mice
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Aberrant neuroplasticity; Temporal lobe epilepsy; Mossy fiber sprouting;
Dystrophic neurites; Beta-secretase; Alzheimer's disease
ID AMYLOID PRECURSOR PROTEIN; TEMPORAL-LOBE EPILEPSY; GATED
SODIUM-CHANNELS; ALZHEIMERS-DISEASE PATHOGENESIS; TRAUMATIC
BRAIN-INJURY; PILOCARPINE MODEL; BETA-SECRETASE; SYNAPTIC PLASTICITY;
MOSSY FIBER; NEURONAL-ACTIVITY
AB The brain is capable of remarkable synaptic reorganization following stress and injury, often using the same molecular machinery that governs neurodevelopment. This form of plasticity is crucial for restoring and maintaining network function. However, neurodegeneration and subsequent reorganization can also play a role in disease pathogenesis, as is seen in temporal lobe epilepsy and Alzheimer's disease. beta-Secretase-1 (BACE1) is a protease known for cleaving beta-amyloid precursor protein into beta-amyloid (A beta), a major constituent in amyloid plaques. Emerging evidence suggests that BACE1 is also involved with synaptic plasticity and nerve regeneration. Here we examined whether BACE1 immunoreactivity (IR) was altered in pilocarpine-induced epileptic CD1 mice in a manner consistent with the synaptic reorganization seen during epileptogenesis. BACE1-IR increased in the CA3 mossy fiber field and dentate inner molecular layer in pilocarpine-induced epileptic mice, relative to controls (saline-treated mice and mice 24-48 h after pilocarpine-status), and paralleled aberrant expression of neuropeptide Y. Regionally increased BACE1-IR also occurred in neuropil in hippocampal area CA1 and in subregions of the amygdala and temporal cortex in epileptic mice, colocalizing with increased IR for growth associated protein 43 (GAP43) and polysialylated-neural cell adhesion molecule (PSA-NCAM), but reduced IR for microtubule-associated protein 2 (MAP2). These findings suggest that BACE1 is involved in aberrant limbic axonal sprouting in a model of temporal lobe epilepsy, warranting further investigation into the role of BACE1 in physiological vs. pathological neuronal plasticity. Published by Elsevier Inc.
C1 [Yan, Xiao-Xin; Cai, Yan; Luo, Xue-Gang] Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
[Cai, Yan; Rose, Gregory M.; Patrylo, Peter R.] So Illinois Univ, Dept Physiol, Carbondale, IL 62901 USA.
[Yan, Xiao-Xin; Rose, Gregory M.; Patrylo, Peter R.] So Illinois Univ, Ctr Integrated Res Cognit & Neural Sci, Carbondale, IL 62901 USA.
[Zhang, Xue-Mei; Rose, Gregory M.; Patrylo, Peter R.] So Illinois Univ, Dept Anat, Carbondale, IL 62901 USA.
[Zhang, Xue-Mei] Harbin Med Univ, Affiliated Hosp 2, Dept Neurol, Harbin 150086, Peoples R China.
[Cai, Huaibin] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Yan, XX (reprint author), Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
EM yanxiaoxin@csu.edu.cn; ppatrylo@siumed.edu
RI Cai, Huaibin/H-3359-2013
OI Cai, Huaibin/0000-0002-8596-6108
FU National Institute of Health [1R21NS056371]; Illinois Department of
Public Health; Southern Illinois University Center for Alzheimer's
disease and related disorders; National Institute on Aging; Central
South University
FX This study was supported by the National Institute of Health
(1R21NS056371 to P.R.P., X.-X.Y.), the Illinois Department of Public
Health (X.-X.Y.), the Southern Illinois University Center for
Alzheimer's disease and related disorders (P.R.P., G.M.R, X.-X.Y.), the
intramural program of the National Institute on Aging (H.C) and the
Central South University (X.-X.Y.).
NR 95
TC 11
Z9 12
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 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD MAY
PY 2012
VL 235
IS 1
BP 228
EP 237
DI 10.1016/j.expneurol.2012.01.003
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 934FZ
UT WOS:000303430400024
PM 22265658
ER
PT J
AU Chen, CM
Hu, ZG
Liu, SB
Tseng, H
AF Chen, Chaomei
Hu, Zhigang
Liu, Shengbo
Tseng, Hung
TI Emerging trends in regenerative medicine: a scientometric analysis in
CiteSpace
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE CiteSpace; co-citation analysis; induced pluripotent stem cells;
regenerative medicine; scientometrics
ID PLURIPOTENT STEM-CELLS; REPROGRAMMING FACTORS; SCIENTIFIC LITERATURE;
HUMAN FIBROBLASTS; DEFINED FACTORS; RESEARCH FRONTS; GENERATION; MOUSE;
STATE; PATIENT
AB Introduction: Regenerative medicine involves research in a number of fields and disciplines such as stem cell research, tissue engineering and biological therapy in general. As research in these areas advances rapidly, it is critical to keep abreast of emerging trends and critical turns of the development of the collective knowledge.
Areas covered: A progressively synthesized network is derived from 35,963 original research and review articles that cite 3875 articles obtained from an initial topic search on regenerative medicine between 2000 and 2011. CiteSpace is used to facilitate the analysis of the intellectual structure and emerging trends.
Expert opinion: A major ongoing research trend is concerned with finding alternative reprogramming techniques as well as refining existing ones for induced pluripotent stem cells (iPSCs). A more recent emerging trend focuses on the structural and functional equivalence between iPSCs and human embryonic stem cells and potential clinical and therapeutic implications on regenerative medicine in a long run. The two trends overlap in terms of what they cite, but they are distinct and have different implications on future research. Visual analytics of the literature provides a valuable, timely, repeatable and flexible approach in addition to traditional systematic reviews so as to track the development of new emerging trends and identify critical evidence.
C1 [Chen, Chaomei] Drexel Univ, Coll Informat Sci & Technol, Philadelphia, PA 19104 USA.
[Hu, Zhigang; Liu, Shengbo] Dalian Univ Technol, WISELAB, Dalian, Peoples R China.
[Tseng, Hung] NIAMSD, NIH, Div Skin & Rheumat Dis, Bethesda, MD 20892 USA.
RP Chen, CM (reprint author), Drexel Univ, Coll Informat Sci & Technol, 3141 Chestnut St, Philadelphia, PA 19104 USA.
EM chaomei.chen@drexel.edu
RI Chen, Chaomei/A-1252-2007
OI Chen, Chaomei/0000-0001-8584-1041
NR 62
TC 45
Z9 56
U1 43
U2 307
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD MAY
PY 2012
VL 12
IS 5
BP 593
EP 608
DI 10.1517/14712598.2012.674507
PG 16
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 936ZA
UT WOS:000303627600009
PM 22443895
ER
PT J
AU Hill, MJ
Levens, ED
Levy, G
Ryan, ME
Csokmay, JM
DeCherney, AH
Whitcomb, BW
AF Hill, Micah J.
Levens, Eric D.
Levy, Gary
Ryan, Mary E.
Csokmay, John M.
DeCherney, Alan H.
Whitcomb, Brian W.
TI The use of recombinant luteinizing hormone in patients undergoing
assisted reproductive techniques with advanced reproductive age: a
systematic review and meta-analysis
SO FERTILITY AND STERILITY
LA English
DT Review
DE Recombinant luteinizing hormone; recombinant follicle stimulating
hormone; in vitro fertilization; assisted reproductive technologies;
advanced reproductive age
ID IN-VITRO FERTILIZATION; FOLLICLE-STIMULATING-HORMONE; PREMATURE
PROGESTERONE ELEVATION; HUMAN MENOPAUSAL GONADOTROPINS; CONTROLLED
OVARIAN STIMULATION; HIGHLY PURIFIED HMG; LH SUPPLEMENTATION;
CONTROLLED-TRIAL; PREGNANCY RATES; ANTAGONIST CYCLES
AB Objective: To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age.
Design: A systematic review and meta-analysis.
Setting: Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age.
Patient(s): Patients 35 years and older undergoing assisted reproduction.
Intervention(s): Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles.
Main Outcome Measure(s): Implantation and clinical pregnancy.
Result(s): Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E-2 on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83).
Conclusion(s): The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. (Fertil Steril (R) 2012;97:1108-14. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Hill, Micah J.; Levens, Eric D.; Levy, Gary; Csokmay, John M.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Levens, Eric D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Ryan, Mary E.] Natl Inst Hlth Lib, Bethesda, MD USA.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 1E-3140, Bethesda, MD 20892 USA.
EM Eric.Levens@Integramed.com
FU National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
FX Supported, in part, by the Program in Reproductive and Adult
Endocrinology, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland.
NR 44
TC 33
Z9 39
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAY
PY 2012
VL 97
IS 5
BP 1108
EP +
DI 10.1016/j.fertnstert.2012.01.130
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 934RA
UT WOS:000303461800029
PM 22365075
ER
PT J
AU Chen, LS
Saccone, NL
Culverhouse, RC
Bracci, PM
Chen, CH
Dueker, N
Han, Y
Huang, HY
Jin, GF
Kohno, T
Ma, JZ
Przybeck, TR
Sanders, AR
Smith, JA
Sung, YJ
Wenzlaff, AS
Wu, C
Yoon, D
Chen, YT
Cheng, YC
Cho, YS
David, SP
Duan, JB
Eaton, CB
Furberg, H
Goate, AM
Gu, DF
Hansen, HM
Hartz, S
Hu, ZB
Kim, YJ
Kittner, SJ
Levinson, DF
Mosley, TH
Payne, TJ
Rao, DC
Rice, JP
Rice, TK
Schwantes-An, TH
Shete, SS
Shi, JX
Spitz, MR
Sun, YV
Tsai, FJ
Wang, JC
Wrensch, MR
Xian, H
Gejman, PV
He, J
Hunt, SC
Kardia, SL
Li, MD
Lin, DX
Mitchell, BD
Park, T
Schwartz, AG
Shen, HB
Wiencke, JK
Wu, JY
Yokota, J
Amos, CI
Bierut, LJ
AF Chen, Li-Shiun
Saccone, Nancy L.
Culverhouse, Robert C.
Bracci, Paige M.
Chen, Chien-Hsiun
Dueker, Nicole
Han, Younghun
Huang, Hongyan
Jin, Guangfu
Kohno, Takashi
Ma, Jennie Z.
Przybeck, Thomas R.
Sanders, Alan R.
Smith, Jennifer A.
Sung, Yun Ju
Wenzlaff, Angie S.
Wu, Chen
Yoon, Dankyu
Chen, Ying-Ting
Cheng, Yu-Ching
Cho, Yoon Shin
David, Sean P.
Duan, Jubao
Eaton, Charles B.
Furberg, Helena
Goate, Alison M.
Gu, Dongfeng
Hansen, Helen M.
Hartz, Sarah
Hu, Zhibin
Kim, Young Jin
Kittner, Steven J.
Levinson, Douglas F.
Mosley, Thomas H.
Payne, Thomas J.
Rao, D. C.
Rice, John P.
Rice, Treva K.
Schwantes-An, Tae-Hwi
Shete, Sanjay S.
Shi, Jianxin
Spitz, Margaret R.
Sun, Yan V.
Tsai, Fuu-Jen
Wang, Jen C.
Wrensch, Margaret R.
Xian, Hong
Gejman, Pablo V.
He, Jiang
Hunt, Steven C.
Kardia, Sharon L.
Li, Ming D.
Lin, Dongxin
Mitchell, Braxton D.
Park, Taesung
Schwartz, Ann G.
Shen, Hongbing
Wiencke, John K.
Wu, Jer-Yuarn
Yokota, Jun
Amos, Christopher I.
Bierut, Laura J.
TI Smoking and Genetic Risk Variation Across Populations of European,
Asian, and African American Ancestry-A Meta-Analysis of Chromosome 15q25
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE smoking; genetics; meta-analysis; cross-population
ID LUNG-CANCER RISK; NICOTINE DEPENDENCE; CAUSAL VARIANTS; HEAVY SMOKING;
ASSOCIATION; POLYMORPHISMS; DISEASE; IDENTIFICATION; BEHAVIOR; CLUSTER
AB Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.251.42, P = 1.1 x 10-17 in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments. Genet. Epidemiol. 36:340351, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Chen, Li-Shiun; Przybeck, Thomas R.; Goate, Alison M.; Hartz, Sarah; Rice, John P.; Wang, Jen C.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Saccone, Nancy L.; Schwantes-An, Tae-Hwi] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Culverhouse, Robert C.; Xian, Hong] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Bracci, Paige M.] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Chen, Chien-Hsiun; Chen, Ying-Ting; Wu, Jer-Yuarn] Acad Sinica, Inst Biomed Sci, Natl Genotyping Ctr, Taipei, Taiwan.
[Chen, Chien-Hsiun; Wu, Jer-Yuarn] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan.
[Dueker, Nicole] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Han, Younghun; Shete, Sanjay S.; Spitz, Margaret R.; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Huang, Hongyan; Sung, Yun Ju; Rao, D. C.; Rice, Treva K.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jin, Guangfu; Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
[Kohno, Takashi] Natl Canc Ctr, Div Genome Biol, Tokyo, Japan.
[Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Sanders, Alan R.; Duan, Jubao; Gejman, Pablo V.] Univ Chicago, N Shore Univ Hlth Syst Res Inst, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA.
[Smith, Jennifer A.; Mosley, Thomas H.; Sun, Yan V.; Kardia, Sharon L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Wenzlaff, Angie S.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Dept Etiol, Beijing 100730, Peoples R China.
[Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Carcinogenesis Canc Inst, Beijing 100730, Peoples R China.
[Yoon, Dankyu; Kim, Young Jin] Seoul Natl Univ, Coll Nat Sci, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea.
[Yoon, Dankyu] Natl Inst Hlth, Ctr Immunol & Pathol, Seoul, South Korea.
[Cheng, Yu-Ching] Univ Maryland, Med Ctr, Dept Med, Baltimore, MD 21201 USA.
[Cho, Yoon Shin; Mitchell, Braxton D.] Natl Inst Hlth, Ctr Genome Sci, Seoul, South Korea.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
[David, Sean P.; Kim, Young Jin] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[David, Sean P.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[David, Sean P.; Eaton, Charles B.] Brown Univ, Dept Family Med, Providence, RI 02912 USA.
[Furberg, Helena] Mem Sloan Kettering Canc Ctr, Dept Epidemiol, New York, NY 10021 USA.
[Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100730, Peoples R China.
[Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, Dongfeng] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Hansen, Helen M.; Wrensch, Margaret R.; Wiencke, John K.] Helen Diller Family Canc Ctr, Neurol Surg Div Epidemiol, San Francisco, CA USA.
[Kittner, Steven J.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Payne, Thomas J.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tsai, Fuu-Jen] China Med Univ, Sch Postbaccalaureate Chinese Med, Taipei, Taiwan.
[He, Jiang] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Hunt, Steven C.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA.
[Park, Taesung] Seoul Natl Univ, Coll Nat Sci, Dept Stat, Seoul 151742, South Korea.
[Yokota, Jun] Natl Canc Ctr, Div Multistep Carcinogenesis, Tokyo, Japan.
RP Chen, LS (reprint author), Washington Univ, Sch Med, Dept Psychiat, Box 8134,660 S Euclid Ave, St Louis, MO 63110 USA.
EM chenli@psychiatry.wustl.edu
RI Tsai, Fuu-Jen/J-4140-2015;
OI David, Sean/0000-0002-4922-2603; Hartz, Sarah/0000-0002-5429-3799;
Mitchell, Braxton/0000-0003-4920-4744; Smith,
Jennifer/0000-0002-3575-5468
FU National Cancer Institute (NCI) [P01 CA089392]; National Human Genome
Research Institute (NHGRI) [U01 HG04422-01]; National Institute on Drug
Abuse (NIDA) [K02 DA021237]; NIDA [HHSN271200477471C,
HHSN271200477451C]; National Institutes of Health (NIH)
[HHSN268200782096]; NIH [MH61675, MH60879, MH81800, MH46276, MH46289,
MH46318, MH79469, MH79470, HHSN268200625226C]; Cancer Prevention
Research Institute of Texas [RP10043]; National Institutes of Health
Genes, Environment and Health Initiative [U01 HG004436]; GENEVA
consortium under GEI; Mid-Atlantic Nutrition and Obesity Research Center
[P30 DK072488]; Office of Research and Development, Medical Research
Service; Baltimore Geriatrics Research, Education, and Clinical Center
of the Department of Veterans Affairs; Division of Adult and Community
Health, Centers for Disease Control; National Institute of Neurological
Disorders and Stroke (NINDS); NIH Office of Research on Women's Health
[R01 NS45012, U01 NS069208-01]; Genetic Association Information Network
(GAIN); Paul Michael Donovan Charitable Foundation; National Center for
Research Resources [U54 RR020278]; National Heart Lung and Blood
Institute (NHLBI) of the National Institutes of Health [HL54457,
HL68737, HL087660]; NHLBI; National Human Genome Research Institute
[U01HG004402]; State Key Basic Research Program [2002CB512902]; Korea
National Institute of Health (Korea Center for Disease Control, Ministry
for Health, Welfare and Family Affairs), Republic of Korea; Consortium
for Large Scale Genome Wide Association Study; National Research
Foundation [KRF-2008-313-C00086]; Ministry of Education, Japan; Ministry
of Health, Labor and Welfare; Academia Sinica Genomic Medicine
Multicenter Study; National Science Council, Taiwan (National Clinical
Core) [NSC97-3112-B-001-014]; National Genotyping Center
[NSC97-3112-B-001-015]; National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, Maryland [U01HL072507];
National Institute of Environmental Health Sciences [R01 ES06717];
National Cancer Institute [R01 CA 52689]; National Heart, Lung, and
Blood Institute, National Institutes of Health, U.S. Department of
Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221];
[KL2RR024994]; [K08DA030398]; [R01DA026911]; [R03DA023166];
[R21DA033827]; [U10]; [UL1RR025005]; [DA 017441]; [02733]
FX Collaborative Genetic Study of Nicotine Dependence (COGEND): We thank
the subjects who participated in this study. We wish to thank Hilary
Davidson, Sherri Fisher, Tracey Richmond, and Heidi Kromrei for
administrative support; and Louis Fox for data analysis. The
Collaborative Genetic Study of Nicotine Dependence (COGEND) study
investigators are Laura Bierut (PI), Michael Brent, Naomi Breslau,
Robert Culverhouse, Alison Goate, Richard Grucza, Dorothy Hatsukami,
Anthony Hinrichs, Eric Johnson, Sharon Murphy, John Rice, Nancy Saccone,
Scott Saccone, Joe Henry Steinbach, Jerry Stitzel, and Jen-Chyong Wang.
MD Anderson: We are grateful for the invaluable contributions of
clinical information and tissue samples by the participants in this
study, as well as for the dedicated work of the research staff at
different clinical sites. Also, we wish to thank Dr. Qing Xu for
performing SNP-typing on our samples. Mid-south Tobacco Family Study
(MSTF): We are grateful for the invaluable contributions of clinical
information and tissue samples by the participants in this study, as
well as for the dedicated work of the research staff at different
clinical sites. Molecular Genetics of Schizophrenia: We thank the study
participants and the research staff at the study sites. Genetic
Epidemiology Network of America (GENOA): Mayo Clinic (Rochester Field
Center and Genotyping Center): Stephen T. Turner, Mariza de Andrade,
Julie Cunningham. University of Texas Health Sciences Center (DNA lab):
Eric Boerwinkle, Megan L. Grove-Gaona. University of Michigan (Analysis
Center): Patricia Peyser, Lawrence Bielak, Wei Zhao. Hypertension
Genetic Epidemiology Network (HyperGEN): University of Utah (Network
Coordinating Center, Field Center, and Molecular Genetics Lab): Steven
C. Hunt, Ph.D. (Network Director and Field Center P.I.); Mark F.
Leppert, Ph.D. (Molecular Genetics P.I.); Jean-Marc Lalouel, M.D., D.Sc;
Robert B. Weiss, Ph.D.; Roger R. Williams, M.D. (late); Janet Hood.
University of Alabama at Birmingham (Field Center): Cora E. Lewis, M.D.,
M.S.P.H. (P.I.); Albert Oberman, M.D., M.P.H.; Donna Arnett, Ph.D.;
Phillip Johnson; Christie Oden. Boston University (Field Center):
Richard H. Myers, Ph.D. (P.I.); R. Curtis Ellison, M.D.; Yuqing Zhang,
M.D.; Jemma B. Wilk, D.Sc.; Luc Djouss, M.D., D.Sc.; Jason M. Laramie;
Greta Lee Splansky, M.S. University of Minnesota (Field Center and
Biochemistry Lab): James S. Pankow, Ph.D. (Field Center P.I.); Michael
B. Miller, Ph.D.; Michael Li, Ph.D.; John H. Eckfeldt, M.D., Ph.D.;
Anthony a. Killeen, M.D., Ph.D.; Catherine Leiendecker-Foster, M.S.;
Jean Bucksa; Greg Rynders. University of North Carolina (Field Center):
Kari E. North, Ph.D. (P.I); Barry I. Freedman, M.D.; Gerardo Heiss, M.D.
Washington University (Data Coordinating Center): D.C. Rao, Ph.D.
(P.I.); Charles Gu, Ph.D.; Treva Rice, Ph.D; Aldi T. Kraja, D.Sc.,
Ph.D.; Gang Shi, Ph.D.; Yun Ju Sung, Ph.D.; Karen L. Schwander, M.S .;
Matthew Brown; Michael A. Province, Ph.D.; Ingrid Borecki, Ph.D. Weil
Cornell Medical College (Echo Reading Center): R.B. Devereux, M.D.;
Giovanni de Simone, M.D., Jonathan N. Bella, M.D. National Heart, Lung,
& Blood Institute: Cashell Jaquish, Ph.D.; Dina Paltoo, Ph.D. ARIC: The
authors thank the staff and participants of the ARIC study for their
important contributions. Japan: We thank Dr. Kouya Shiraishi for his
help on genotype data processing. GenSalt: The GenSalt Study Steering
Committee: Dongfeng Gu, JiangHe (Chair), James E. Hixson, Cashell E.
Jaquish, Depei Liu, DC Rao, Paul K. Whelton, and Zhijian Yao.; GenSalt
Collaborative Research Group: Tulane University Health Sciences Center,
NewOrleans, USA: Jiang He (I), LydiaA. Bazzano, Chung- Shiuan Chen, Jing
Chen, Lee Hamm, Paul Muntner, Kristi Reynolds, Jaqueline R. Reuben, Paul
K. Whelton, and Wenjie Yang. Washington University School of Medicine,
St. Louis, USA: DC Rao (PI), Matthew Brown, Charles Gu, Hongyan Huang,
Treva Rice, Karen Schwander, Gang Shi, and Yun Ju Sung. Chinese Academy
of Medical Sciences, Beijing, China: Dongfeng Gu (PI), Jie Cao, Jichun
Chen, Xiufang Duan, Jianfeng Huang, Jinghan Huang, Jianxin Li, Depei
Liu, Donghua Liu, Enchun Pan, YangWei, and Xiqui Wu. Shandong Academy
ofMedical Sciences, Shandong, China: Fanghong Lu (PI), Shikuan Jin,
Qingjie Meng, Fan Wu, and Yingxin Zhao; Shandong Center for Diseases
Control and Prevention, Shandong, China: Jixiang Ma (PI), Weika Li, and
Jiyu Zhang; Zhengzhou University: Dongsheng Hu (PI), Yaxin Ding,
HongweiWen, Meixi Zhang, and Weidong Zhang; Xinle Traditional
ChineseMedicine Hospital, Hebei, China: Xu Ji (PI), Rongyan Li, Haijun
Zu; Nanjing University of Medical Sciences, Jiangsu, China: Cailiang Yao
(PI), Yongchao Li, Chong Shen, and Jiayi Zhou; Xi'an Jiaotong
University, Shanxi, China: Jianjun Mu (PI), Enrang Chen, Qinzhou Huang,
and Man Wang. Chinese National Human Genome Center at Beijing: Zhi- Jian
Yao (PI), Shufeng Chen, Dongfeng Gu, Hongfan Li, Laiyuan Wang, Penghua
Zhang, Qi Zhao. University of Texas Health Sciences Center at Houston:
James E. Hixson (PI) and Lawrence C. Shimmin. National Heart, Lung, and
Blood Institute: Cashell E. Jaquish. Women's Health Initiative: This
manuscript was prepared in collaboration with investigators of the WHI
and has been reviewed and approved (MS1453) by the Women's Health
Initiative (WHI) Publications & Presentations Committee. The authors
thank Charles Kooperberg and the WHI investigators and staff and study
participants for making the program possible. WHI investigators are
listed at http://www.whiscience.org/ publications/WHI_investigators_
shortlist. pdf. Collaborative Genetic Study of Nicotine Dependence
(COGEND): The COGEND contribution was supported by the National Cancer
Institute (NCI; P01 CA089392), The National Human Genome Research
Institute (NHGRI; U01 HG04422-01), and the National Institute on Drug
Abuse (NIDA; K02 DA021237). COGEND genotyping was in part performed
under NIDA Contract HHSN271200477471C; phenotypic and genotypic data are
stored in the NIDA Center for Genetic Studies (NCGS) at
http://zork.wustl.edu/ under NIDA Contract HHSN271200477451C (PIs J
Tischfield and J Rice); genotyping services were also provided by the
Center for Inherited Disease Research (CIDR), which is fully funded
through a federal contract from the National Institutes of Health (NIH)
to The Johns Hopkins University, contract number HHSN268200782096. Dr.
LiShiun Chen was supported by KL2RR024994 and K08DA030398. Support was
also provided by R01DA026911, R03DA023166, and R21DA033827. MD Anderson:
Research was supported by NIH grants U19CA148127, R01CA121197S2,
R01CA141716, R01CA127219, CA121197, R01CA133996, P30CA16672, P50CA70907,
R01CA55769 and Cancer Prevention Research Institute of Texas grant
RP10043. Midsouth Tobacco Family Study (MSTF): This project is supported
in part by NIH Grant R01 DA012844 (PI: Ming Li). Wayne State University
and the Karmanos Cancer Institute: Family Health Study; Women's
Epidemiology of Lung Disease; EXHALE (Exploring Health Ancestry and Lung
Epidemiology): This research was supported through NIH grants
R01CA060691 and R01CA87895, and NIH contract PC35145.; University of
Maryland: GEOS: The GEOS Study was supported by the National Institutes
of Health Genes, Environment and Health Initiative (GEI) Grant U01
HG004436, as part of the GENEVA consortium under GEI, with additional
support provided by the Mid-Atlantic Nutrition and Obesity Research
Center (P30 DK072488); and the Office of Research and Development,
Medical Research Service, and the Baltimore Geriatrics Research,
Education, and Clinical Center of the Department of Veterans Affairs.
Genotyping services were provided by the Johns Hopkins University Center
for Inherited Disease Research (CIDR), which is fully funded through a
federal contract from the National Institutes of Health to the Johns
Hopkins University (contract number HHSN268200782096C). Assistance with
data cleaning was provided by the GENEVA Coordinating Center (U01 HG
004446; PI Bruce SWeir). Study recruitment and collection of datasets
were supported by a Cooperative Agreement with the Division of Adult and
Community Health, Centers for Disease Control and by grants from the
National Institute of Neurological Disorders and Stroke (NINDS) and the
NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01).
Molecular Genetics of Schizophrenia: This study was supported by NIH R01
grants (MH67257 to Nancy G. Buccola, MH59588 to Bryan J. Mowry, MH59571
to Pablo V. Gejman, MH59565 to Robert Freedman, MH59587 to Farooq Amin,
MH60870 to William F. Byerley, MH59566 to Donald W. Black, MH59586 to
Jeremy M. Silverman, MH61675 to Douglas F. Levinson, MH60879 to C.
Robert Cloninger, and MH81800 to Pablo V. Gejman), NIH U01 grants
(MH46276 to C. Robert Cloninger, MH46289 to Charles Kaufmann, MH46318 to
Ming T. Tsuang, MH79469 to Pablo V. Gejman, and MH79470 to Douglas F.
Levinson), the Genetic Association Information Network (GAIN), and by
The Paul Michael Donovan Charitable Foundation. Genotyping was carried
out by the Center for Genotyping and Analysis at the Broad Institute of
Harvard and MIT (Stacy Gabriel and Daniel B. Mirel), which is supported
by grant U54 RR020278 from the National Center for Research Resources.
Genotyping of half of the EA sample and almost all the AA sample was
carried out with support from GAIN. The GAIN quality control team
(Goncalo R. Abecasis and Justin Paschall) made important contributions
to the project. We thank Shaun Purcell for assistance with PLINK.
Genetic Epidemiology Network of America (GENOA): The Genetic
Epidemiology Network of Arteriopathy phenotyping and genome-wide
genotyping is supported by the National Heart Lung and Blood Institute
(NHLBI) of the National Institutes of Health (HL54457, HL68737, and
HL087660). Hypertension Genetic Epidemiology Network (HyperGEN): The
Hypertension Genetic Epidemiology Network is funded by cooperative
agreements (U10) with NHLBI: HL54471, HL54472, HL54473, HL54495,
HL54496, HL54497, HL54509, HL54515. ARIC: The Atherosclerosis Risk in
Communities Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute (NHLBI) contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694;
National Human Genome Research Institute contract U01HG004402; and
National Institutes of Health contract HHSN268200625226C. Infrastructure
was partly supported by Grant Number UL1RR025005, a component of the
National Institutes of Health and NIH Roadmap for Medical Research.;
Nanjing and Beijing: This work was supported by the Chinese National
Natural Science Foundation grant 30230080 (Hongbing Shen) and the State
Key Basic Research Program grants 2002CB512902 (Hongbing Shen). Dr.
Dongxin Lin was supported by State Key Basic Research Program grant
2004CB518701. KARE (Korea Association Resource): The KARE data analyzed
in this study were obtained from the Korean Genome Analysis Project
(4845-301) which was funded by a grant from the Korea National Institute
of Health (Korea Center for Disease Control, Ministry for Health,
Welfare and Family Affairs), Republic of Korea. The work of TP was
supported by the Consortium for Large Scale Genome Wide Association
Study, the National Research Foundation (KRF-2008-313-C00086) and the
Brain Korea 21 Project of the Ministry of Education, Japan:
Grants-in-Aid from the Ministry of Health, Labor and Welfare for the
3rd-term Comprehensive 10-year Strategy for Cancer Control and for
Cancer Research (19-9 and 19S-1). Taiwan: This study was supported by
Academia Sinica Genomic Medicine Multicenter Study and National Research
Program for Genomic Medicine, National Science Council, Taiwan (National
Clinical Core, NSC97-3112-B-001-014 and National Genotyping Center,
NSC97-3112-B-001-015). GenSalt: The Genetic Epidemiology Network of Salt
Sensitivity is supported by a cooperative agreement project Grant
(U01HL072507) from the National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, Maryland. University of
California San Francisco: This work was supported by the National
Institute of Environmental Health Sciences [R01 ES06717]; and the
National Cancer Institute [R01 CA 52689 to MW]. Women's Health
Initiative: The WHI program is funded by the National Heart, Lung, and
Blood Institute, National Institutes of Health, U.S. Department of
Health and Human Services through contracts N01WH22110, 24152, 32100-2,
32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26,
42129-32, and 44221. SPD is supported by DA 017441 and 02733. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. CONFLICT OF
INTEREST DISCLOSURE: LB Bierut, AM Goate, JP Rice, and JC Wang are
listed as inventors on Issued U.S. Patent. 8,080,371, "Markers for
Addiction" covering the use of certain SNPs in determining the
diagnosis, prognosis, and treatment of addiction. Ming Li serves as a
scientific advisor to ADial Pharmaceuticals.
NR 33
TC 38
Z9 39
U1 0
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2012
VL 36
IS 4
BP 340
EP 351
DI 10.1002/gepi.21627
PG 12
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 932VZ
UT WOS:000303319900006
PM 22539395
ER
PT J
AU Shi, JX
Li, P
AF Shi, Jianxin
Li, Peng
TI An Integrative Segmentation Method for Detecting Germline Copy Number
Variations in SNP Arrays
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE copy number variations; segmentation method; change point detection; B
allele frequency
ID HIDDEN-MARKOV MODEL; GENOTYPING DATA; CGH DATA; POPULATION; PLATFORMS;
SEQUENCES; DELETIONS; WAVES; MAP
AB Germline copy number variations (CNVs) are a major source of genetic variation in humans. In large-scale studies of complex diseases, CNVs are usually detected from data generated by single nucleotide polymorphism (SNP) genotyping arrays. In this paper, we develop an integrative segmentation method, SegCNV, for detecting CNVs integrating both log R ratio (LRR) and B allele frequency (BAF). Based on simulation studies, SegCNV had modestly better power to detect deletions and substantially better power to detect duplications compared with circular binary segmentation (CBS) that relies purely on LRRs; and it had better power to detect deletions and a comparable performance to detect duplications compared with PennCNV and QuantiSNP. In two Hapmap subjects with deep sequence data available as a gold standard, SegCNV detected more true short deletions than PennCNV and QuantiSNP. For 21 short duplications validated experimentally in the AGRE dataset, SegCNV, QuantiSNP, and PennCNV detected all of them while CBS detected only three. SegCNV is much faster than the HMM-based (where HMM is hidden Markov model) methods, taking only several seconds to analyze genome-wide data for one subject. Genet. Epidemiol. 36:373-383, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Shi, Jianxin; Li, Peng] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20854 USA.
RP Shi, JX (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20854 USA.
EM jianxin.shi@nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
at the National Institutes of Health; National Institute of Mental
Health [1U24MH081810]
FX The authors are supported by the Intramural Research Program, Division
of Cancer Epidemiology and Genetics, National Cancer Institute at the
National Institutes of Health. We gratefully acknowledge the resources
provided by the Autism Genetic Resource Exchange (AGRE) Consortium and
the participating AGRE families. The Autism Genetic Resource Exchange is
a program of Autism Speaks and is supported, in part, by grant
1U24MH081810 from the National Institute of Mental Health to C.M.L.
(PI). This study utilized the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD (http://biowulf.nih.gov). The authors declare no
conflicts of interest.
NR 25
TC 3
Z9 4
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2012
VL 36
IS 4
BP 373
EP 383
DI 10.1002/gepi.21631
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 932VZ
UT WOS:000303319900010
PM 22539397
ER
PT J
AU Rasmussen-Torvik, LJ
Guo, XQ
Bowden, DW
Bertoni, AG
Sale, MM
Yao, J
Bluemke, DA
Goodarzi, MO
Chen, YI
Vaidya, D
Raffel, LJ
Papanicolaou, GJ
Meigs, JB
Pankow, JS
AF Rasmussen-Torvik, Laura J.
Guo, Xiuqing
Bowden, Donald W.
Bertoni, Alain G.
Sale, Michele M.
Yao, Jie
Bluemke, David A.
Goodarzi, Mark O.
Chen, Y. Ida
Vaidya, Dhananjay
Raffel, Leslie J.
Papanicolaou, George J.
Meigs, James B.
Pankow, James S.
TI Fasting Glucose GWAS Candidate Region Analysis Across Ethnic Groups in
the Multiethnic Study of Atherosclerosis (MESA)
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE GWAS; fasting glucose; SNP
ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; PLASMA-GLUCOSE;
INSULIN-RESISTANCE; MTNR1B; POLYMORPHISM; VARIANT; GENE; INDIVIDUALS;
POPULATION
AB Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these single nucleotide polymorphisms (SNPs) and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian genome-wide association studies (GWAS) across multiple ethnicities in the Multiethnic Study of Atherosclerosis (MESA). Nondiabetic MESA participants with fasting glucose measured at the baseline exam and with GWAS genotyping were included; 2,349 Caucasians, 664 individuals of Chinese descent, 1,366 African Americans, and 1,171 Hispanics. Genotype data were generated from the Affymetrix 6.0 array and imputation in IMPUTE. Fasting glucose was regressed on SNP dosage data in each ethnic group adjusting for age, gender, MESA study center, and ethnic-specific principal components. SNPs from the three gene regions with the strongest associations to fasting glucose in previous Caucasian GWAS (MTNR1B / GCK / G6PC2) were examined in depth. There was limited power to replicate associations in other ethnic groups due to smaller allele frequencies and limited sample size; SNP associations may also have differed across ethnic groups due to differing linkage disequilibrium patterns with causal variants. rs10830963 in MTNR1B and rs4607517 in GCK demonstrated consistent magnitude and direction of association with fasting glucose across ethnic groups, although the associations were often not nominally significant. In conclusion, certain SNPs in MTNR1B and GCK demonstrate consistent effects across four racial and ethnic groups, narrowing the putative region for these causal variants. Genet. Epidemiol. 36:384-391, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Guo, Xiuqing; Yao, Jie; Goodarzi, Mark O.; Chen, Y. Ida; Raffel, Leslie J.] Med Genet Res Inst, Los Angeles, CA USA.
[Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27103 USA.
[Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Ctr Clin, NIH, Bethesda, MD USA.
[Vaidya, Dhananjay] Johns Hopkins Sch Med, Dept Gen Internal Med, Baltimore, MD USA.
[Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Div Gen Med, Boston, MA USA.
[Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Rasmussen-Torvik, LJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM ljrtorvik@northwestern.edu
OI Bluemke, David/0000-0002-8323-8086; Vaidya,
Dhananjay/0000-0002-7164-1601; Pankow, James/0000-0001-7076-483X
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159,
N01-HC-95169, R01HL071051, R01HL071205, R01HL071250, R01HL071251,
R01HL071252, R01HL071258, R01HL071259]; NIDDK [K24 DK080140]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI).
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. Genotyping was funded by the following
NHLBI grants: R01HL071051, R01HL071205, R01HL071250, R01HL071251,
R01HL071252, R01HL071258, R01HL071259. JBM is supported by NIDDK K24
DK080140.
NR 29
TC 14
Z9 15
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2012
VL 36
IS 4
BP 384
EP 391
DI 10.1002/gepi.21632
PG 8
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 932VZ
UT WOS:000303319900011
PM 22508271
ER
PT J
AU Murray, T
Taub, MA
Ruczinski, I
Scott, AF
Hetmanski, JB
Schwender, H
Patel, P
Zhang, TX
Munger, RG
Wilcox, AJ
Ye, XQ
Wang, H
Wu, T
Wu-Chou, YH
Shi, B
Jee, SH
Chong, S
Yeow, V
Murray, JC
Marazita, ML
Beaty, TH
AF Murray, Tanda
Taub, Margaret A.
Ruczinski, Ingo
Scott, Alan F.
Hetmanski, Jacqueline B.
Schwender, Holger
Patel, Poorav
Zhang, Tian Xiao
Munger, Ronald G.
Wilcox, Allen J.
Ye, Xiaoqian
Wang, Hong
Wu, Tao
Wu-Chou, Yah Huei
Shi, Bing
Jee, Sun Ha
Chong, Samuel
Yeow, Vincent
Murray, Jeffrey C.
Marazita, Mary L.
Beaty, Terri H.
TI Examining Markers in 8q24 to Explain Differences in Evidence for
Association With Cleft Lip With/Without Cleft Palate Between Asians and
Europeans
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE cleft lip with; without cleft palate; 8q24; genome-wide association;
imputation
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; CHROMOSOME 8Q24;
CANCER-RISK; POPULATION; VARIANTS
AB In a recent genome-wide association study (GWAS) from an international consortium, evidence of linkage and association in chr8q24 was much stronger among nonsyndromic cleft lip/palate (CL/P) case-parent trios of European ancestry than among trios of Asian ancestry. We examined marker information content and haplotype diversity across 13 recruitment sites (from Europe, United States, and Asia) separately, and conducted principal components analysis (PCA) on parents. As expected, PCA revealed large genetic distances between Europeans and Asians, and a north-south cline from Korea to Singapore in Asia, with Filipino parents forming a somewhat distinct Southeast Asian cluster. Hierarchical clustering of SNP heterozygosity revealed two major clades consistent with PCA results. All genotyped SNPs giving P < 10-6 in the allelic transmission disequilibrium test (TDT) showed higher heterozygosity in Europeans than Asians. On average, European ancestry parents had higher haplotype diversity than Asians. Imputing additional variants across chr8q24 increased the strength of statistical evidence among Europeans and also revealed a significant signal among Asians (although it did not reach genome-wide significance). Tests for SNP-population interaction were negative, indicating the lack of strong signal for 8q24 in families of Asian ancestry was not due to any distinct genetic effect, but could simply reflect low power due to lower allele frequencies in Asians. Genet. Epidemiol. 36:392399, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Murray, Tanda; Hetmanski, Jacqueline B.; Patel, Poorav; Zhang, Tian Xiao; Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Taub, Margaret A.; Ruczinski, Ingo; Schwender, Holger] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Scott, Alan F.] Johns Hopkins Sch Med, Inst Med Genet, Baltimore, MD USA.
[Schwender, Holger] TU Dortmund Univ, Fac Stat, Dortmund, Germany.
[Munger, Ronald G.] Utah State Univ, Logan, UT 84322 USA.
[Wilcox, Allen J.] NIEHS, NIH, Epidemiol Branch, Durham, NC USA.
[Ye, Xiaoqian] Wuhan Univ, Sch Stomatol, Wuhan 430072, Peoples R China.
[Ye, Xiaoqian] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Wang, Hong; Wu, Tao] Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China.
[Wu-Chou, Yah Huei] Chang Gung Mem Hosp, Tao Yuan, Taiwan.
[Shi, Bing] Sichuan Univ, W China Coll Stomatol, State Key Lab Oral Dis, Chengdu 610064, Peoples R China.
[Jee, Sun Ha] Yonsei Univ, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea.
[Chong, Samuel] Natl Univ Singapore, Singapore 117548, Singapore.
[Yeow, Vincent] KK Womens & Childrens Hosp, Singapore, Singapore.
[Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Childrens Hosp, Iowa City, IA 52242 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA.
RP Beaty, TH (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM tbeaty@jhsph.edu
RI Chong, Samuel/D-8098-2015;
OI Wilcox, Allen/0000-0002-3376-1311
FU National Human Genome Research Institute (NHGRI); US National Institutes
of Health (NIH) [HHSN268200782096C]; NIDCR [U01-DE-018993]; NIH,
National Institute of Environmental Health Sciences; [R01-DE-014581];
[R37-DE08559]; [R01-DE016148]; [P50-DE016215]; [R21-DE016930]
FX We sincerely thank all of the families at each recruitment site for
participating in this international study, and we gratefully acknowledge
the invaluable assistance of clinical, field, and laboratory staff whose
contributions made this work possible. Funding to support data
collection, genotyping, and analysis came from several sources, some to
individual investigators and some to the cleft consortium itself. The
International Cleft Consortium was part of the Gene, Environment
Association Studies (GENEVA) Consortium funded by the National Human
Genome Research Institute (NHGRI) to enhance communication and
collaboration among researchers conducting genome-wide studies of
complex diseases. Our group benefited greatly from the work and efforts
of the entire consortium, especially the Coordinating Center (directed
by B. Weir and C. Laurie of the University of Washington) in data
cleaning and preparation for submission to the Database for Genotypes
and Phenotypes (dbGaP). We also acknowledge the leadership of T. Manolio
of NHGRI and E. Harris of National Institute of Dental and Craniofacial
Research (NIDCR). Genotyping services were provided by the Center for
Inherited Disease Research (CIDR), funded through a federal contract
from the US National Institutes of Health (NIH) to Johns Hopkins
University (contract number HHSN268200782096C), and we wish to thank
Drs. K. Doheny, E. W. Pugh, and H. Ling in particular. The GWAS was
supported by the NIDCR through U01-DE-018993; "International Consortium
to Identify Genes & Interactions Controlling Oral Clefts," TH Beaty, PI.
Funding for individual investigators include: R01-DE-014581 (T.H.B.);
R37-DE08559 (J.C.M., M.L.M.), R01-DE016148 (M.L.M.), P50-DE016215
(J.C.M., M.L.M.), R21-DE016930 (M.L.M.). Smile Train Foundation
supported data collection in Chengdu (B.S.). This research was supported
in part by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (A.J.W.). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIDCR, nor the NIH.
NR 22
TC 12
Z9 13
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2012
VL 36
IS 4
BP 392
EP 399
DI 10.1002/gepi.21633
PG 8
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 932VZ
UT WOS:000303319900012
PM 22508319
ER
PT J
AU Sampson, JN
Jacobs, K
Wang, ZM
Yeager, M
Chanock, S
Chatterjee, N
AF Sampson, Joshua N.
Jacobs, Kevin
Wang, Zhaoming
Yeager, Meredith
Chanock, Stephen
Chatterjee, Nilanjan
TI A Two-Platform Design for Next Generation Genome-Wide Association
Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE GWAS; case-control study; power; study design; Omni2.5; imputation
ID CANCER SCREENING TRIAL; GENOTYPE IMPUTATION; SUSCEPTIBILITY LOCI;
MISSING GENOTYPES; METAANALYSIS; PROSTATE; RISK; PREVENTION; ACCURACY;
POWER
AB Genome-wide association studies (GWAS) have been successful in their search for common genetic variants associated with complex traits and diseases. With new advances in array technologies together with available genetic reference sets, the next generation of GWAS will extend the search for associations with uncommon SNPs (1% <= MAF <= 10%). Two possible approaches are genotyping all participants, a prohibitively expensive option for large GWAS, or using a combination of genotyping and imputation. Here, we consider a two platform method that genotypes all participants on a standard genotyping array, designed to identify common variants, and then supplements that data by genotyping only a small proportion of the participants on a platform that has higher coverage for uncommon SNPs. This subset of the study population is then included as part of the imputation reference set. To demonstrate the use of this two-platform design, we evaluate its potential efficiency using a newly available dataset containing 756 individuals genotyped on both the Illumina Human OmniExpress and Omni2.5 Quad. Although genotyping all individuals on the denser array would be ideal, we find that genotyping only 100 individuals on this array, in combination with imputation, leads to only a modest loss of power for detecting associations. However, the loss of power due to imputation can be more substantial if the relative risks for rare variants are significantly larger than those previously observed for common variants. Genet. Epidemiol. 36:400-408, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Sampson, Joshua N.; Chatterjee, Nilanjan] NCI, Biostat Branch, DCEG, Rockville, MD 20852 USA.
[Jacobs, Kevin; Wang, Zhaoming; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, DCEG, Gaithersburg, MD USA.
[Chanock, Stephen] NCI, Lab Translat Genom, Gaithersburg, MD USA.
RP Sampson, JN (reprint author), NCI, Biostat Branch, DCEG, 6120 Execut Blvd,8038 Rockville, Rockville, MD 20852 USA.
EM joshua.sampson@nih.gov
NR 40
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2012
VL 36
IS 4
BP 401
EP 409
DI 10.1002/gepi.21634
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 932VZ
UT WOS:000303319900013
ER
PT J
AU Kong, HDH
Oh, J
Deming, C
Conlan, S
Grice, EA
Beatson, MA
Nomicos, E
Polley, EC
Komarow, HD
Murray, PR
Turner, ML
Segre, JA
AF Kong, Heidi H.
Oh, Julia
Deming, Clay
Conlan, Sean
Grice, Elizabeth A.
Beatson, Melony A.
Nomicos, Effie
Polley, Eric C.
Komarow, Hirsh D.
Murray, Patrick R.
Turner, Maria L.
Segre, Julia A.
CA NISC Comparative Sequence Program
TI Temporal shifts in the skin microbiome associated with disease flares
and treatment in children with atopic dermatitis
SO GENOME RESEARCH
LA English
DT Article
ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; PARTY DIAGNOSTIC-CRITERIA;
ANTIMICROBIAL PEPTIDES; BINDING PROTEIN; SCORAD INDEX; ECZEMA;
COLONIZATION; EPIDERMIDIS; BACTERIAL; INFECTIONS
AB Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
C1 [Kong, Heidi H.; Beatson, Melony A.; Nomicos, Effie; Turner, Maria L.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Oh, Julia; Deming, Clay; Conlan, Sean; Grice, Elizabeth A.; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Polley, Eric C.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Komarow, Hirsh D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequence Program] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Murray, Patrick R.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Kong, HDH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@mail.nih.gov
RI Conlan, Sean/B-4401-2008;
OI Conlan, Sean/0000-0001-6848-3465; Kong, Heidi/0000-0003-4424-064X;
Grice, Elizabeth/0000-0003-3939-2200
FU NIH CC; NCI; NHGRI; National Institutes of Health [1UH2AR057504-01,
4UH3AR057504-02]; [1K99AR059222]
FX We thank Mark C. Udey, Eric Green, and Evan Snitkin for helpful
discussions; Pamela Thomas, Deborah Schoenfeld, Joie Davis, Roselyn
Epps, Celeste Nelson, and Donna Gaskins for underlying contributions;
and especially the patients and volunteers. This work was supported by
NIH CC, NCI, and NHGRI Intramural Research Programs, and in part by
1K99AR059222 (H.H.K.). Sequencing and clinical research support was
funded by grants from the National Institutes of Health Common Fund
Human Microbiome Project (1UH2AR057504-01 and 4UH3AR057504-02).
NR 55
TC 255
Z9 264
U1 7
U2 75
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2012
VL 22
IS 5
BP 850
EP 859
DI 10.1101/gr.131029.111
PG 10
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 933NU
UT WOS:000303369600005
PM 22310478
ER
PT J
AU Li, JF
Akagi, K
Hu, YJ
Trivett, AL
Hlynialuk, CJW
Swing, DA
Volfovsky, N
Morgan, TC
Golubeva, Y
Stephens, RM
Smith, DE
Symer, DE
AF Li, Jingfeng
Akagi, Keiko
Hu, Yongjun
Trivett, Anna L.
Hlynialuk, Christopher J. W.
Swing, Deborah A.
Volfovsky, Natalia
Morgan, Tamara C.
Golubeva, Yelena
Stephens, Robert M.
Smith, David E.
Symer, David E.
TI Mouse endogenous retroviruses can trigger premature transcriptional
termination at a distance
SO GENOME RESEARCH
LA English
DT Article
ID COPY NUMBER VARIATION; PEPT2 NULL MICE; TRANSPOSABLE ELEMENTS;
GENE-EXPRESSION; CHOROID-PLEXUS; ALTERNATIVE POLYADENYLATION; PARTICLE
GENES; HUMAN GENOME; HOST GENES; WILD-TYPE
AB Endogenous retrotransposons have caused extensive genomic variation within mammalian species, but the functional implications of such mobilization are mostly unknown. We mapped thousands of endogenous retrovirus (ERV) germline integrants in highly divergent, previously unsequenced mouse lineages, facilitating a comparison of gene expression in the presence or absence of local insertions. Polymorphic ERVs occur relatively infrequently in gene introns and are particularly depleted from genes involved in embryogenesis or that are highly expressed in embryonic stem cells. Their genomic distribution implies ongoing negative selection due to deleterious effects on gene expression and function. A polymorphic, intronic ERV at Slc15a2 triggers up to 49-fold increases in premature transcriptional termination and up to 39-fold reductions in full-length transcripts in adult mouse tissues, thereby disrupting protein expression and functional activity. Prematurely truncated transcripts also occur at Polr1a, Spon1, and up to similar to 5% of other genes when intronic ERV polymorphisms are present. Analysis of expression quantitative trait loci (eQTLs) in recombinant BxD mouse strains demonstrated very strong genetic associations between the polymorphic ERV in cis and disrupted transcript levels. Premature polyadenylation is triggered at genomic distances up to >12.5 kb upstream of the ERV, both in cis and between alleles. The parent of origin of the ERV is associated with variable expression of nonterminated transcripts and differential DNA methylation at its 5'-long terminal repeat. This study defines an unexpectedly strong functional impact of ERVs in disrupting gene transcription at a distance and demonstrates that ongoing retrotransposition can contribute significantly to natural phenotypic diversity.
C1 [Li, Jingfeng; Akagi, Keiko; Hlynialuk, Christopher J. W.; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
[Li, Jingfeng; Akagi, Keiko; Hlynialuk, Christopher J. W.; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Hu, Yongjun; Smith, David E.] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA.
[Trivett, Anna L.] NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA.
[Swing, Deborah A.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Volfovsky, Natalia; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, Frederick, MD 21702 USA.
[Morgan, Tamara C.; Golubeva, Yelena] NCI, Histotechnol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA.
[Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Biomed Informat, Columbus, OH 43210 USA.
RP Symer, DE (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
EM david.symer@osumc.edu
RI Symer, David/E-4173-2011
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; NIH [R01-GM035498]; National Cancer Institute
[HHSN261200800001E]; Ohio State University Comprehensive Cancer Center
FX We thank Drs. Albert de la Chapelle, Neal Copeland, and Maura Gillison
for helpful comments; Robert Williams, Lu Lu, and Jesse F. Ingels
(University of Tennessee) for help with the Gene Network and providing
several BxD RI mouse strain genomic DNA samples; Holly Morris, Rob
Koogle, and Sherry Rausch (National Cancer Institute) for superb
maintenance of our mouse colony; Xiaolin Wu and Hongling Liao (SAIC
Frederick) for assistance with exon microarray experiments; Clive Evans
(Virginia Bioinformatics Institute) for 454 sequencing; and Richard
Frederickson (SAIC Frederick) and Anthony Baker (OSU) for graphical
illustration. This project was supported by the Intramural Research
Program, Center for Cancer Research, National Cancer Institute, National
Institutes of Health (to J.L., K.A., A.L.T., D.A.S., T.C.M., D.E.Sy.);
NIH research grant R01-GM035498 (to Y.H. and D.E.Sm.); contract no.
HHSN261200800001E by the National Cancer Institute to SAIC, Inc. (to
N.V., T.C.M., Y.G., and R.M.S.); and by The Ohio State University
Comprehensive Cancer Center (to J.L., K.A., C.J.W.H., and D.E.Sy.). We
thank the Ohio Supercomputer Center for providing computational
resources (grant PAS0425-2 to K.A. and D.E.Sy.). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. NCI-Frederick and OSU are accredited by the Association
for Assessment and Accreditation of Laboratory Animal Care International
and follow the U.S. Public Health Service Policy for the Care and Use of
Laboratory Animals. Animal care was provided in accordance with the
procedures outlined in the "Guide for Care and Use of Laboratory
Animals" (National Research Council, 1996, National Academy Press,
Washington, DC). Mouse studies were performed following protocols
approved by the Animal Care and Use Committee, NCI Frederick or by the
Institutional Animal Care and Use Committee, OSU.
NR 73
TC 26
Z9 26
U1 1
U2 14
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2012
VL 22
IS 5
BP 870
EP 884
DI 10.1101/gr.130740.111
PG 15
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 933NU
UT WOS:000303369600007
PM 22367191
ER
PT J
AU Khil, PP
Smagulova, F
Brick, KM
Camerini-Otero, RD
Petukhova, GV
AF Khil, Pavel P.
Smagulova, Fatima
Brick, Kevin M.
Camerini-Otero, R. Daniel
Petukhova, Galina V.
TI Sensitive mapping of recombination hotspots using sequencing-based
detection of ssDNA
SO GENOME RESEARCH
LA English
DT Article
ID MEIOTIC RECOMBINATION; SACCHAROMYCES-CEREVISIAE; HOT-SPOTS; STRAND
EXCHANGE; DNA REVEALS; HUMAN-SPERM; MOUSE; YEAST; INITIATION; PROTEIN
AB Meiotic DNA double-stranded breaks (DSBs) initiate genetic recombination in discrete areas of the genome called recombination hotspots. DSBs can be directly mapped using chromatin immunoprecipitation followed by sequencing (ChIP-seq). Nevertheless, the genome-wide mapping of recombination hotspots in mammals is still a challenge due to the low frequency of recombination, high heterogeneity of the germ cell population, and the relatively low efficiency of ChIP. To overcome these limitations we have developed a novel method-single stranded DNA (ssDNA) sequencing (SSDS)-that specifically detects protein-bound single-stranded DNA at DSB ends. SSDS comprises a computational framework for the specific detection of ssDNA-derived reads in a sequencing library and a new library preparation procedure for the enrichment of fragments originating from ssDNA. The use of our technique reduces the nonspecific double-stranded DNA (dsDNA) background >10-fold. Our method can be extended to other systems where the identification of ssDNA or DSBs is desired.
C1 [Khil, Pavel P.; Brick, Kevin M.; Camerini-Otero, R. Daniel] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Smagulova, Fatima; Petukhova, Galina V.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM camerini@ncifcrf.gov; gpetukhova@usuhs.mil
RI Smagulova, Fatima/K-5459-2015;
OI Brick, Kevin/0000-0002-9596-6400; Smagulova, Fatima/0000-0001-6883-1968;
Khil, Pavel/0000-0002-4903-8777
FU NIDDK from the March of Dimes Foundation [5-FY07-667]; NIH from NIGMS
[1R01GM084104-01A1]; USUHS [FS71HU, R071HU, CS71HU]
FX We thank Peggy Hsieh and Michael Lichten for helpful discussion and
Shaila Sharmeen for help with high-throughput sequencing. This study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov). This research was supported by the NIDDK
Intramural Research Program; by Basil O'Connor Starter Scholar Research
Award Grant No. 5-FY07-667 from the March of Dimes Foundation (G.V.P.);
NIH grant 1R01GM084104-01A1 from NIGMS (G.V.P.); New Investigator
Start-up Grants FS71HU, R071HU, and CS71HU from USUHS (G.V.P.).
NR 30
TC 21
Z9 21
U1 1
U2 19
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2012
VL 22
IS 5
BP 957
EP 965
DI 10.1101/gr.130583.111
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 933NU
UT WOS:000303369600014
PM 22367190
ER
PT J
AU Filipovych, R
Resnick, SM
Davatzikos, C
AF Filipovych, Roman
Resnick, Susan M.
Davatzikos, Christos
TI JointMMCC: Joint Maximum-Margin Classification and Clustering of Imaging
Data
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Aging; clustering; magnetic resonance imaging (MRI); semi-supervised
classification
ID DIMENSIONAL PATTERN-CLASSIFICATION; MILD COGNITIVE IMPAIRMENT;
ALZHEIMERS-DISEASE; BIPOLAR DISORDER; BRAIN ATROPHY; OLDER-ADULTS; MCI
PATIENTS; SCHIZOPHRENIA; AD; DECLINE
AB A number of conditions are characterized by pathologies that form continuous or nearly-continuous spectra spanning from the absence of pathology to very pronounced pathological changes (e.g., normal aging, mild cognitive impairment, Alzheimer's). Moreover, diseases are often highly heterogeneous with a number of diagnostic subcategories or subconditions lying within the spectra (e.g., autism spectrum disorder, schizophrenia). Discovering coherent subpopulations of subjects within the spectrum of pathological changes may further our understanding of diseases, and potentially identify subconditions that require alternative or modified treatment options. In this paper, we propose an approach that aims at identifying coherent subpopulations with respect to the underlying MRI in the scenario where the condition is heterogeneous and pathological changes form a continuous spectrum. We describe a joint maximum-margin classification and clustering (JointMMCC) approach that jointly detects the pathologic population via semi-supervised classification, as well as disentangles heterogeneity of the pathological cohort by solving a clustering subproblem. We propose an efficient solution to the nonconvex optimization problem associated with JointMMCC. We apply our proposed approach to an medical resonance imaging study of aging, and identify coherent subpopulations (i.e., clusters) of cognitively less stable adults.
C1 [Filipovych, Roman; Davatzikos, Christos] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, Biomed Res Ctr 04B317, Baltimore, MD 21224 USA.
RP Filipovych, R (reprint author), Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA.
EM roman.filipovych@uphs.upenn.edu; christos.davatzikos@uphs.upenn.edu
FU National Institutes of Health (NIH), National Institute on Aging (NIA);
[R01-AG14971]; [N01-AG-3-2124]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute on Aging
(NIA), and R01-AG14971, N01-AG-3-2124, N01-AG-3-2124. Asterisk indicates
corresponding author.
NR 65
TC 6
Z9 7
U1 3
U2 12
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2012
VL 31
IS 5
BP 1124
EP 1140
DI 10.1109/TMI.2012.2186977
PG 17
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 935ES
UT WOS:000303502400012
PM 22328179
ER
PT J
AU Wang, SJ
McKenna, MT
Nguyen, TB
Burns, JE
Petrick, N
Sahiner, B
Summers, RM
AF Wang, Shijun
McKenna, Matthew T.
Nguyen, Tan B.
Burns, Joseph E.
Petrick, Nicholas
Sahiner, Berkman
Summers, Ronald M.
TI Seeing Is Believing: Video Classification for Computed Tomographic
Colonography Using Multiple-Instance Learning
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Computed tomographic colonography (CTC); multiple-instance learning;
semidefinite programming; video analysis
ID CT COLONOGRAPHY; AIDED DETECTION; POLYP DETECTION; VIRTUAL COLONOSCOPY;
OBJECT RECOGNITION; COLONIC POLYPS; SYSTEM; FEATURES; ENDOSCOPY;
EVOLUTION
AB In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods.
C1 [Wang, Shijun; McKenna, Matthew T.; Nguyen, Tan B.; Summers, Ronald M.] NIH, Bethesda, MD 20892 USA.
[Burns, Joseph E.] Univ Calif Irvine, Dept Radiol Sci, Orange, CA 92868 USA.
[Petrick, Nicholas; Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Summers, RM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU NIH Clinical Center; Food and Drug Administration
FX This work was supported by the Intramural Research Programs of the NIH
Clinical Center and the Food and Drug Administration. No official
endorsement by the National Institutes of Health or the Food and Drug
Administration of any equipment or product of any company mentioned in
the publication should be inferred. Asterisk indicates corresponding
author.
NR 53
TC 9
Z9 9
U1 0
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2012
VL 31
IS 5
BP 1141
EP 1153
DI 10.1109/TMI.2012.2187304
PG 13
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 935ES
UT WOS:000303502400013
PM 22552333
ER
PT J
AU Imboden, M
Bouzigon, E
Curjuric, I
Ramasamy, A
Kumar, A
Hancock, DB
Wilk, JB
Vonk, JM
Thun, GA
Siroux, V
Nadif, R
Monier, F
Gonzalez, JR
Wjst, M
Heinrich, J
Loehr, LR
Franceschini, N
North, KE
Altmuller, J
Koppelman, GH
Guerra, S
Kronenberg, F
Lathrop, M
Moffatt, MF
O'Connor, GT
Strachan, DP
Postma, DS
London, SJ
Schindler, C
Kogevinas, M
Kauffmann, F
Jarvis, DL
Demenais, F
Probst-Hensch, NM
AF Imboden, Medea
Bouzigon, Emmanuelle
Curjuric, Ivan
Ramasamy, Adaikalavan
Kumar, Ashish
Hancock, Dana B.
Wilk, Jemma B.
Vonk, Judith M.
Thun, Gian A.
Siroux, Valerie
Nadif, Rachel
Monier, Florent
Gonzalez, Juan R.
Wjst, Matthias
Heinrich, Joachim
Loehr, Laura R.
Franceschini, Nora
North, Kari E.
Altmueller, Janine
Koppelman, Gerard H.
Guerra, Stefano
Kronenberg, Florian
Lathrop, Mark
Moffatt, Miriam F.
O'Connor, George T.
Strachan, David P.
Postma, Dirkje S.
London, Stephanie J.
Schindler, Christian
Kogevinas, Manolis
Kauffmann, Francine
Jarvis, Debbie L.
Demenais, Florence
Probst-Hensch, Nicole M.
TI Genome-wide association study of lung function decline in adults with
and without asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; cohort studies; genome-wide association; lung function decline;
heterogeneity
ID OBSTRUCTIVE PULMONARY-DISEASE; S-TRANSFERASE M1; LARGE-SCALE;
GENERAL-POPULATION; CANDIDATE GENE; POLYMORPHISMS; LOCI; PHENOTYPES;
CHILDREN; VARIANTS
AB Background: Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung function.
Objective: We conducted the first genome-wide association study on the age-related decrease in FEV1 and its ratio to forced vital capacity (FVC) stratified a priori by asthma status.
Methods: Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV1 and FEV1/FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study).
Results: Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV1 decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 x 10(-6); replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV1/FVC ratio decrease in asthmatic participants (P = 5.3 x 10(-8)), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline.
Conclusions: Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status. (J Allergy Clin Immunol 2012;129:1218-28.)
C1 [Imboden, Medea; Curjuric, Ivan; Kumar, Ashish; Thun, Gian A.; Schindler, Christian; Probst-Hensch, Nicole M.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Imboden, Medea; Curjuric, Ivan; Kumar, Ashish; Thun, Gian A.; Schindler, Christian; Probst-Hensch, Nicole M.] Univ Basel, CH-4003 Basel, Switzerland.
[Bouzigon, Emmanuelle; Monier, Florent; Demenais, Florence] INSERM, UMRS 946, Paris, France.
[Bouzigon, Emmanuelle; Monier, Florent; Lathrop, Mark; Demenais, Florence] Fdn Jean Dausset, CEPH, Paris, France.
[Bouzigon, Emmanuelle; Monier, Florent; Demenais, Florence] Univ Paris 07, Inst Univ Hematol, Paris, France.
[Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
[Ramasamy, Adaikalavan; Jarvis, Debbie L.] MRC HPA Ctr Environm & Hlth, London, England.
[Kumar, Ashish] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Hancock, Dana B.; London, Stephanie J.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Hancock, Dana B.] Res Triangle Inst Int, Behav Hlth Epidemiol Program, Res Triangle Pk, NC USA.
[Wilk, Jemma B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA.
[Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp,Groningen Res Inst Asthma, NL-9700 AB Groningen, Netherlands.
[Siroux, Valerie] INSERM, U823, Team Environm Epidemiol Appl Reprod & Resp Hlth, Grenoble, France.
[Siroux, Valerie] Univ Grenoble 1, Grenoble, France.
[Nadif, Rachel; Kauffmann, Francine] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Resp & Environm Epidemiol Team, Villejuif, France.
[Nadif, Rachel; Kauffmann, Francine] Univ Paris 11, UMRS 1018, Villejuif, France.
[Gonzalez, Juan R.; Guerra, Stefano; Kogevinas, Manolis] Ctr Res Environm Epidemiol, Barcelona, Spain.
[Gonzalez, Juan R.; Guerra, Stefano; Kogevinas, Manolis] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Wjst, Matthias; Heinrich, Joachim] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Loehr, Laura R.; Franceschini, Nora] Univ N Carolina Chapel Hill, UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina Chapel Hill, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Altmueller, Janine] Univ Cologne, CCG, Cologne, Germany.
[Guerra, Stefano] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA.
[Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria.
[Lathrop, Mark] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France.
[O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London WC1E 7HU, England.
[Guerra, Stefano; Kogevinas, Manolis] IMIM Municipal Inst Med Res, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
RP Probst-Hensch, NM (reprint author), SwissTPH, Socinstr 57, CH-4002 Basel, Switzerland.
EM Nicole.Probst@unibas.ch
RI Ramasamy, Adaikalavan/G-2632-2010; Jarvis, Deborah/E-6494-2011; siroux,
valerie/N-1865-2013; Demenais, Florence/G-3298-2013; Kronenberg,
Florian/B-1736-2008; Schindler, Christian/D-3472-2015; Nadif,
Rachel/R-2876-2016; Kogevinas, Manolis/C-3918-2017;
OI London, Stephanie/0000-0003-4911-5290; Ramasamy,
Adaikalavan/0000-0002-7598-2892; Kumar, Ashish/0000-0002-7075-5930;
O'Connor, George/0000-0002-6476-3926; Hancock, Dana/0000-0003-2240-3604;
Demenais, Florence/0000-0001-8361-0936; Kronenberg,
Florian/0000-0003-2229-1120; Nadif, Rachel/0000-0003-4938-9339; Thun,
Gian Andri/0000-0003-4436-3455
FU National Institutes of Health/National Heart, Lung, and Blood Institute;
Flight Attendant Medical Research Institute; Netherlands Asthma
Foundation; Top Institute Pharma; AstraZeneca; French Agency of
Research; French Agency for Environmental and Occupational Health and
Safety; INSERM-Ministry of Research "Cohortes et Collections"
FX Disclosure of potential conflict of interest: J. B. Wilk has received
research support from the National Institutes of Health/National Heart,
Lung, and Blood Institute and the Flight Attendant Medical Research
Institute. G. H. Koppelman has received research support from the
Netherlands Asthma Foundation. D. S. Postma is a consultant for Nycomed
and has received research support from the Top Institute Pharma and
AstraZeneca. F. Kauffmann has received research support from the French
Agency of Research, French Agency for Environmental and Occupational
Health and Safety, and INSERM-Ministry of Research "Cohortes et
Collections." The rest of the authors declare that they have no relevant
conflicts of interest.
NR 62
TC 48
Z9 48
U1 1
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAY
PY 2012
VL 129
IS 5
BP 1218
EP 1228
DI 10.1016/j.jaci.2012.01.074
PG 11
WC Allergy; Immunology
SC Allergy; Immunology
GA 934CG
UT WOS:000303418000007
PM 22424883
ER
PT J
AU Liang, GQ
Barker, T
Xie, ZH
Charles, N
Rivera, J
Druey, KM
AF Liang, Genqing
Barker, Tolga
Xie, Zhihui
Charles, Nicolas
Rivera, Juan
Druey, Kirk M.
TI Naive T cells sense the cysteine protease allergen papain through
protease-activated receptor 2 and propel T(H)2 immunity
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Chemokines; basophils; chemotaxis; T(H)2; allergens
ID HELPER TYPE-2 RESPONSE; DENDRITIC CELLS; IN-VIVO; IL-4 PRODUCTION;
BASOPHILS; DIFFERENTIATION; EXPRESSION; COMPLEXES; CYTOKINES; CCL17
AB Background: Sensitization to protease allergens, such as papain, or helminth infection is associated with basophil recruitment to draining lymph nodes (LNs). Basophils have the capacity to present antigen to naive T cells and promote T(H)2 differentiation directly or indirectly through IL-4 production.
Objective: We studied how papain induces basophil migration to LNs and the contribution of various leukocytes to papain-induced immune responses.
Methods: We immunized mice in the footpad with papain and studied leukocyte recruitment and inflammatory cytokine and chemokine production in the draining popliteal LNs.
Results: Papain directly activated naive T cells through protease-activated receptor (PAR) 2 to initiate a chemokine/cytokine program that includes CCL17, CCL22, and IL-4. Papain-triggered innate immune responses were dependent on both CD4 T cells and PAR2 and were strongly reduced in the absence of CCR4, the primary receptor for CCL17/CCL22.
Conclusion: These results elucidate a novel innate allergen-recognition pathway mediated by naive T cells through PAR2, which provide an immediate source of chemokines and IL-4 upstream of basophils and antigen-restricted T(H)2 differentiation. PAR2 antagonism might thus hold promise for the treatment of allergic disease. (J Allergy Clin Immunol 2012;129:1377-86.)
C1 [Liang, Genqing; Barker, Tolga; Xie, Zhihui; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Charles, Nicolas; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 10 Ctr Dr,Rm 11N242, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; National Institute of Arthritis and Musculoskeletal
and Skin Diseases [AI000939]
FX Supported in part by the Intramural Research Programs of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases, and National Institute of Arthritis and Musculoskeletal and
Skin Diseases (grant no. AI000939 LAD to K. M. D.).
NR 38
TC 19
Z9 19
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAY
PY 2012
VL 129
IS 5
BP 1377
EP U282
DI 10.1016/j.jaci.2012.02.035
PG 23
WC Allergy; Immunology
SC Allergy; Immunology
GA 934CG
UT WOS:000303418000029
PM 22460072
ER
PT J
AU Udey, MC
AF Udey, Mark C.
TI Epidermal Langerhans cells tune skin reactivity to contact allergens
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID DERMAL DENDRITIC CELLS; T-CELLS; HYPERSENSITIVITY; DERMATITIS; DISTINCT;
SENSITIZATION; TOLERANCE; RESPONSES; ABLATION; IMMUNITY
AB Allergic contact dermatitis is a common disorder that has fascinated dermatologists and immunologists for decades. Extensive studies of contact sensitivity reactions in mice established a mechanistic paradigm that has been revisited in recent years, and the involvement of Langerhans cells (LCs), a population of epidermal dendritic cells, in immune responses to epicutaneously applied antigens has been questioned. In this issue of the JCI, Gomez de Aguero et al. describe an elegant series of experiments that implicate LCs in tolerance induction, positioning these cells as key regulators of immunologic barrier function.
C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA.
RP Udey, MC (reprint author), NCI, Dermatol Branch, CCR, NIH, Bldg 10,Room 12N238, Bethesda, MD 20892 USA.
EM udey@helix.nih.gov
FU Intramural NIH HHS
NR 23
TC 1
Z9 2
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAY
PY 2012
VL 122
IS 5
BP 1602
EP 1605
DI 10.1172/JCI63190
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 935BG
UT WOS:000303491400008
PM 22523061
ER
PT J
AU Estes, JD
AF Estes, Jacob D.
TI Enhancing immune responses to limit chronic immune activation during SIV
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID CD8 T-CELLS; CHRONIC INFECTION; RHESUS MACAQUES; PD-1 BLOCKADE;
VIRUS-INFECTION; HIV-INFECTION; EXPRESSION; VACCINATION; EXHAUSTION;
DISEASE
AB The persistent immune activation that is typical of HIV-1 and Sly infection results in exhaustion and dysfunction of T and B cells; in T cells, this is marked by increased expression and signaling through the inhibitory receptor programmed death-1 (PD-1). Targeting this exhaustion pathway could result in improved antiviral immune responses, but there have been concerns that it would also lead to increased inflammation and immunopathology. In this issue of the JCI, Dyavar Shetty et al. demonstrate that blocking PD-1 actually reduced proinflammatory responses and improved immunity in the gut of SIV-infected rhesus macaques, suggesting that this might have therapeutic potential to prevent opportunistic infections in HIV-infected patients.
C1 NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Estes, JD (reprint author), NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM estesj@mail.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; PHS
HHS [HHSN261200800001E]
NR 21
TC 5
Z9 5
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAY
PY 2012
VL 122
IS 5
BP 1611
EP 1614
DI 10.1172/JCI63389
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 935BG
UT WOS:000303491400011
PM 22523060
ER
PT J
AU Bibollet-Ruche, F
Heigele, A
Keele, BF
Easlick, JL
Decker, JM
Takehisa, J
Learn, G
Sharp, PM
Hahn, BH
Kirchhoff, F
AF Bibollet-Ruche, Frederic
Heigele, Anke
Keele, Brandon F.
Easlick, Juliet L.
Decker, Julie M.
Takehisa, Jun
Learn, Gerald
Sharp, Paul M.
Hahn, Beatrice H.
Kirchhoff, Frank
TI Efficient SIVcpz replication in human lymphoid tissue requires viral
matrix protein adaptation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 GROUP O; PRIMATE LENTIVIRUSES;
NONPANDEMIC HIV-1; WILD CHIMPANZEES; HUMAN TETHERIN; CELL-SURFACE;
EX-VIVO; GAG; INFECTION
AB SIVs infecting wild-living apes in west central Africa have crossed the species barrier to humans on at least four different occasions, one of which spawned the AIDS pandemic. Although the chimpanzee precursor of pandemic HIV-1 strains must have been able to infect humans, the capacity of SIVcpz strains to replicate in human lymphoid tissues (HLTs) is not known. Here, we show that SIVcpz strains from two chimpanzee subspecies are capable of replicating in human tonsillary explant cultures, albeit only at low titers. However, SIVcpz replication in HLT was significantly improved after introduction of a previously identified human-specific adaptation at position 30 in the viral Gag matrix protein. An Arg or Lys at this position significantly increased SIVcpz replication in HLT, while the same mutation reduced viral replication in chimpanzee-derived CD4(+) T cells. Thus, naturally occurring SIVcpz strains are capable of infecting HLTs, the major site of HIV-1 replication in vivo. However, efficient replication requires the acquisition of a host-specific adaptation in the viral matrix protein. These results identify Gag matrix as a major determinant of SIVcpz replication fitness in humans and suggest a critical role in the emergence of HIV/AIDS.
C1 [Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Heigele, Anke; Kirchhoff, Frank] Univ Ulm, Med Ctr, Inst Mol Virol, D-89081 Ulm, Germany.
[Keele, Brandon F.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Easlick, Juliet L.; Decker, Julie M.; Takehisa, Jun; Learn, Gerald] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Sharp, Paul M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Hahn, BH (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
EM bhahn@upenn.edu; frank.kirchhoff@uni-ulm.de
RI Sharp, Paul/F-5783-2010
OI Sharp, Paul/0000-0001-9771-543X
FU NIH [R21 AI080364, R01 A150529, R01 A158715, P30 Al27767]; Yerkes
Regional Primate Research Center [RR000165]; Bristol Myers Freedom;
Deutsche Forschungsgemeinschaft
FX We thank Matthias H. Kraus, Rebecca S. Rudicell, Martha Mayer, and
Birgit Ott for technical assistance. This work was supported in part by
the NIH (R21 AI080364, RO1 A150529, R01 A158715, P30 Al27767), the
Yerkes Regional Primate Research Center (RR000165), the Bristol Myers
Freedom to Discover Program, and the Deutsche Forschungsgemeinschaft.
NR 60
TC 15
Z9 15
U1 0
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAY
PY 2012
VL 122
IS 5
BP 1644
EP 1652
DI 10.1172/JCI61429
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 935BG
UT WOS:000303491400014
PM 22505456
ER
PT J
AU Khadra, A
Yan, ZH
Coddou, C
Tomic, M
Sherman, A
Stojilkovic, SS
AF Khadra, Anmar
Yan, Zonghe
Coddou, Claudio
Tomic, Melanija
Sherman, Arthur
Stojilkovic, Stanko S.
TI Gating properties of the P2X2a and P2X2b receptor channels: Experiments
and mathematical modeling
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID P2X(2) RECEPTOR; PERMEABILITY DYNAMICS; CYTOSOLIC DOMAIN; ION-CHANNEL;
DESENSITIZATION; IDENTIFICATION; TRANSDUCTION; ACTIVATION; EXPRESSION
AB Adenosine triphosphate (ATP)-gated P2X2 receptors exhibit two opposite activation-dependent changes, pore dilation and pore closing (desensitization), through a process that is incompletely understood. To address this issue and to clarify the roles of calcium and the C-terminal domain in gating, we combined biophysical and mathematical approaches using two splice forms of receptors: the full-size form (P2X2aR) and the shorter form missing 69 residues in the C-terminal domain (P2X2bR). Both receptors developed conductivity for N-methyl-D-glucamine within 2-6 s of ATP application. However, pore dilation was accompanied with a decrease rather than an increase in the total conductance, which temporally coincided with rapid and partial desensitization. During sustained agonist application, receptors continued to desensitize in calcium-independent and calcium-dependent modes. Calcium-independent desensitization was more pronounced in P2X2bR, and calcium-dependent desensitization was more pronounced in P2X2aR. In whole cell recording, we also observed use-dependent facilitation of desensitization of both receptors. Such behavior was accounted for by a 16-state Markov kinetic model describing ATP binding/unbinding and activation/desensitization. The model assumes that naive receptors open when two to three ATP molecules bind and undergo calcium-independent desensitization, causing a decrease in the total conductance, or pore dilation, causing a shift in the reversal potential. In calcium-containing media, receptor desensitization is facilitated and the use-dependent desensitization can be modeled by a calcium-dependent toggle switch. The experiments and the model together provide a rationale for the lack of sustained current growth in dilating P2X2Rs and show that receptors in the dilated state can also desensitize in the presence of calcium.
C1 [Khadra, Anmar; Sherman, Arthur] NIDDKD, Lab Biol Modeling, Bethesda, MD 20892 USA.
[Yan, Zonghe; Coddou, Claudio; Tomic, Melanija; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Khadra, Anmar] McGill Univ, Dept Physiol, Montreal, PQ H3A 1Y6, Canada.
RP Sherman, A (reprint author), NIDDKD, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM asherman@nih.gov
RI Tomic, Melanija/C-3371-2016
FU National Institutes of Health, National Institute of Child Health and
Human Development; National Institute of Diabetes and Digestive and
Kidney Diseases
FX The authors were supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Child Health and
Human Development (to Z. Yan, M. Tomic, C. Coddou, and S.S.
Stojilkovic), and National Institute of Diabetes and Digestive and
Kidney Diseases (to A. Khadra and A. Sherman).
NR 26
TC 13
Z9 13
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD MAY
PY 2012
VL 139
IS 5
BP 333
EP 348
DI 10.1085/jgp.201110716
PG 16
WC Physiology
SC Physiology
GA 934TF
UT WOS:000303468900002
PM 22547664
ER
PT J
AU Zhao, HY
Berger, AJ
Brown, PH
Kumar, J
Balbo, A
May, CA
Casillas, E
Laue, TM
Patterson, GH
Mayer, ML
Schuck, P
AF Zhao, Huaying
Berger, Anthony J.
Brown, Patrick H.
Kumar, Janesh
Balbo, Andrea
May, Carrie A.
Casillas, Ernesto, Jr.
Laue, Thomas M.
Patterson, George H.
Mayer, Mark L.
Schuck, Peter
TI Analysis of high-affinity assembly for AMPA receptor amino-terminal
domains
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID FLUORESCENCE CORRELATION SPECTROSCOPY; SEDIMENTATION
EQUILIBRIUM-ANALYSIS; PROTEIN-PROTEIN INTERACTIONS; ANALYTICAL
ULTRACENTRIFUGATION; DETECTED SEDIMENTATION; SUBUNIT ARRANGEMENT;
CRYSTAL-STRUCTURE; NMDA RECEPTORS; CELL-LINE; VELOCITY
AB Analytical ultracentrifugation (AUC) and steady-state fluorescence anisotropy were used to measure the equilibrium dissociation constant (K-d) for formation of dimers by the amino-terminal domains (ATDs) of the GluA2 and GluA3 subtypes of AMPA receptor. Previous reports on GluA2 dimerization differed in their estimate of the monomer-dimer K-d by a 2,400-fold range, with no consensus on whether the ATD forms tetramers in solution. We find by sedimentation velocity (SV) analysis performed using absorbance detection a narrow range of monomer-dimer K-d values for GluA2, from 5 to 11 nM for six independent experiments, with no detectable formation of tetramers and no effect of glycosylation or the polypeptide linker connecting the ATD and ligand-binding domains; for GluA3, the monomer-dimer K-d was 5.6 mu M, again with no detectable tetramer formation. For sedimentation equilibrium (SE) experiments, a wide range of K-d values was obtained for GluA2, from 13 to 284 nM, whereas for GluA3, the K-d of 3.1 mu M was less than twofold different from the SV value. Analysis of cell contents after the similar to 1-week centrifuge run by silver-stained gels revealed low molecular weight GluA2 breakdown products. Simulated data for SE runs demonstrate that the apparent K-d for GluA2 varies with the extent of proteolysis, leading to artificially high K-d values. SV experiments with fluorescence detection for GluA2 labeled with 5,6-carboxyfluorescein, and fluorescence anisotropy measurements for GluA2 labeled with DyLight405, yielded K-d values of 5 and 11 nM, consistent with those from SV with absorbance detection. However, the sedimentation coefficients measured by AUC using absorbance and fluorescence systems were strikingly different, and for the latter are not consistent with hydrodynamic protein models. Thus, for unknown reasons, the concentration dependence of sedimentation coefficients obtained with fluorescence detection SV may be unreliable, limiting the usefulness of this technique for quantitative analysis.
C1 [Berger, Anthony J.; Kumar, Janesh; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
[Casillas, Ernesto, Jr.; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, Bethesda, MD 20892 USA.
[May, Carrie A.; Laue, Thomas M.] Univ New Hampshire, Dept Biochem, Durham, NH 03824 USA.
RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mark.mayer@nih.gov; schuckp@mail.nih.gov
RI Zhao, Huaying/F-5716-2012; Mayer, Mark/H-5500-2013;
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Child Health and Human Development; National
Institute of Biomedical Imaging and Bioengineering, NIH, Department of
Health and Human Services
FX This work was supported by the intramural research programs of National
Institute of Child Health and Human Development and National Institute
of Biomedical Imaging and Bioengineering, NIH, Department of Health and
Human Services.
NR 55
TC 26
Z9 26
U1 0
U2 11
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD MAY
PY 2012
VL 139
IS 5
BP 371
EP 388
DI 10.1085/jgp.201210770
PG 18
WC Physiology
SC Physiology
GA 934TF
UT WOS:000303468900005
PM 22508847
ER
PT J
AU Kepka, DL
Ulrich, AK
Coronado, GD
AF Kepka, Deanna L.
Ulrich, Angela K.
Coronado, Gloria D.
TI Low Knowledge of the Three-Dose HPV Vaccine Series among Mothers of
Rural Hispanic Adolescents
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Hispanic mothers; Hispanic adolescents; HPV vaccine uptake; cervical
cancer; rural Hispanics; HPV vaccine education
ID HUMAN-PAPILLOMAVIRUS VACCINATION; UNITED-STATES; ACCEPTANCE
AB Background. Few previous investigations on correlates of HPV vaccine uptake have included Hispanics, a group known to have a disproportionately high risk of cervical cancer. Methods. Rural Hispanic mothers of daughters aged 9-17 (n=78) were recruited at local community events to participate in a standardized Spanish-language survey that examined factors related to vaccine uptake. Results. Approximately 35% of the mothers reported that their daughter had received at least one dose of the vaccine. Mothers who had heard of the HPV vaccine were more likely to have a vaccinated daughter (p<.01). Mothers who thought their daughter's father would approve were more likely to have a vaccinated daughter (p=.004). Contrary to expectation, parents who believed that only one injection is necessary were more likely to have a vaccinated daughter (p=.009). Conclusions. HPV vaccine education programs that target both parents are needed to ensure that Hispanic parents receive the complete HPV vaccine regimen.
C1 [Kepka, Deanna L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ulrich, Angela K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Coronado, Gloria D.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
RP Kepka, DL (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4017,Mail Stop Code 7344, Bethesda, MD 20892 USA.
EM deanna.kepka@nih.gov
FU AHRQ HHS [T32 HS013853]; NCI NIH HHS [U01 CA114633, R25 CA92408]
NR 18
TC 15
Z9 15
U1 1
U2 7
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD MAY
PY 2012
VL 23
IS 2
BP 626
EP 635
PG 10
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 934EY
UT WOS:000303427600013
PM 22643612
ER
PT J
AU Takai, S
Sabzevari, H
Farsaci, B
Schlom, J
Greiner, JW
AF Takai, Shinji
Sabzevari, Helen
Farsaci, Benedetto
Schlom, Jeffrey
Greiner, John W.
TI Distinct Effects of Saracatinib on Memory CD8(+) T Cell Differentiation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN CARCINOEMBRYONIC ANTIGEN; SRC/ABL KINASE INHIBITOR; CEA TRANSGENIC
MICE; IN-VIVO; INFLUENZA NUCLEOPROTEIN; ANTITUMOR IMMUNITY;
COMPLEX-FORMATION; DENDRITIC CELLS; SRC INHIBITOR; ACTIVATION
AB Immunologic memory involving CD8(+) T cells is a hallmark of an adaptive Ag-specific immune response and constitutes a critical component of protective immunity. Designing approaches that enhance long-term T cell memory would, for the most part, fortify vaccines and enhance host protection against infectious diseases and, perhaps, cancer immunotherapy. A better understanding of the cellular programs involved in the Ag-specific T cell response has led to new approaches that target the magnitude and quality of the memory T cell response. In this article, we show that T cells from TCR transgenic mice for the nucleoprotein of influenza virus NP68 exhibit the distinct phases-priming, expansion, contraction, and memory-of an Ag-specific T cell response when exposed in vitro to the cognate peptide. Saracatinib, a specific inhibitor of Src family kinases, administered at low doses during the expansion or contraction phases, increased CD62L(high)/CD44(high) central memory CD8(+) T cells and IFN-gamma production but suppressed immunity when added during the priming phase. These effects by saracatinib were not accompanied by the expected decline of Src family kinases but were accompanied by Akt-mammalian target of rapamycin suppression and/or mediated via another pathway. Increased central memory cells by saracatinib were recapitulated in mice using a poxvirus-based influenza vaccine, thus underscoring the importance of dose and timing of the inhibitor in the context of memory T cell differentiation. Finally, vaccine plus saracatinib treatment showed better protection against tumor challenge. The immune-potentiating effects on CD8(+) T cells by a low dose of saracatinib might afford better protection from pathogens or cancer when combined with vaccine. The Journal of Immunology, 2012, 188: 4323-4333.
C1 [Takai, Shinji; Sabzevari, Helen; Farsaci, Benedetto; Schlom, Jeffrey; Greiner, John W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10,Room 8B09,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jg117s@nih.gov
RI Farsaci, Benedetto/L-9837-2014
OI Farsaci, Benedetto/0000-0001-8275-2561
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 50
TC 4
Z9 4
U1 1
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
IS 9
BP 4323
EP 4333
DI 10.4049/jimmunol.1101439
PG 11
WC Immunology
SC Immunology
GA 932OH
UT WOS:000303299900024
PM 22450814
ER
PT J
AU Falanga, YT
Chaimowitz, NS
Charles, N
Finkelman, FD
Pullen, NA
Barbour, S
Dholaria, K
Faber, T
Kolawole, M
Huang, BN
Odom, S
Rivera, J
Carlyon, J
Conrad, DH
Spiegel, S
Oskeritzian, CA
Ryan, JJ
AF Falanga, Yves T.
Chaimowitz, Natalia S.
Charles, Nicolas
Finkelman, Fred D.
Pullen, Nicholas A.
Barbour, Suzanne
Dholaria, Kevin
Faber, Travis
Kolawole, Motunrayo
Huang, Bernice
Odom, Sandra
Rivera, Juan
Carlyon, Jason
Conrad, Daniel H.
Spiegel, Sarah
Oskeritzian, Carole A.
Ryan, John J.
TI Lyn but Not Fyn Kinase Controls IgG-Mediated Systemic Anaphylaxis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FC-EPSILON-RI; MAST-CELL ACTIVATION; CHRONIC ALLERGIC INFLAMMATION;
GAMMA-RIII; TYROSINE KINASE; NEGATIVE REGULATION; CYTOKINE PRODUCTION;
DEFICIENT MICE; IMPAIRED DEGRANULATION; LUPUS-ERYTHEMATOSUS
AB Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of Fc epsilon RI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to Fc gamma R stimulation by IgG/Ag complexes. We have investigated the contribution of Fyn and Lyn tyrosine kinases to Fc gamma RIIb and Fc gamma RIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). We found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38, and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils, and macrophages resulted in Fyn- and Lyn-regulated mediator release in vitro. Fc gamma R-mediated activation was enhanced in Lyn-deficient (knockout [KO]) cells, but decreased in Fyn KO cells, compared with wild-type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features whereas no change was observed for Fyn KO mice, compared with wild-type littermates. Intriguingly, we establish that mast cells account for most serum histamine in IgG-induced PSA. Taken together, our findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies. The Journal of Immunology, 2012, 188: 4360-4368.
C1 [Falanga, Yves T.; Pullen, Nicholas A.; Dholaria, Kevin; Faber, Travis; Kolawole, Motunrayo; Ryan, John J.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
[Chaimowitz, Natalia S.; Barbour, Suzanne; Huang, Bernice; Carlyon, Jason; Conrad, Daniel H.] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
[Charles, Nicolas] Univ Paris 07, Fac Med Xavier Bichat, INSERM, U699, F-75870 Paris 18, France.
[Finkelman, Fred D.] Cincinnati Vet Affairs Med Ctr, Res Serv, Cincinnati, OH 45220 USA.
[Finkelman, Fred D.] Univ Cincinnati, Coll Med, Div Immunol, Cincinnati, OH 45267 USA.
[Finkelman, Fred D.] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
[Odom, Sandra; Rivera, Juan] NIAMSD, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA.
[Spiegel, Sarah; Oskeritzian, Carole A.] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
RP Ryan, JJ (reprint author), Virginia Commonwealth Univ, Dept Biol, 1000 W Cary St, Richmond, VA 23284 USA.
EM jjryan@vcu.edu
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health; National Institutes of Health
[IR01AI59638, U19A1077435, KO1AR053186]; Veterans Affairs Merit Grant
FX This work was supported by the intramural research program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health (to J.R.), and National Institutes of
Health Grants IR01AI59638 and U19A1077435 (to JR.), KO1AR053186 (to
C.A.O.), and a Veterans Affairs Merit Grant (to F.D.F.).
NR 74
TC 16
Z9 16
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
IS 9
BP 4360
EP 4368
DI 10.4049/jimmunol.1003223
PG 9
WC Immunology
SC Immunology
GA 932OH
UT WOS:000303299900028
PM 22450804
ER
PT J
AU Luz, NF
Andrade, BB
Feijo, DF
Araujo-Santos, T
Carvalho, GQ
Andrade, D
Abanades, DR
Melo, EV
Silva, AM
Brodskyn, CI
Barral-Netto, M
Barral, A
Soares, RP
Ameida, RP
Bozza, MT
Borges, VM
AF Luz, Nivea F.
Andrade, Bruno B.
Feijo, Daniel F.
Araujo-Santos, Theo
Carvalho, Graziele Q.
Andrade, Daniela
Abanades, Daniel R.
Melo, Enaldo V.
Silva, Angela M.
Brodskyn, Claudia I.
Barral-Netto, Manoel
Barral, Aldina
Soares, Rodrigo P.
Ameida, Roque P.
Bozza, Marcelo T.
Borges, Valeria M.
TI Heme Oxygenase-1 Promotes the Persistence of Leishmania chagasi
Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN VISCERAL LEISHMANIASIS; TUMOR-NECROSIS-FACTOR; CARBON-MONOXIDE;
HEMOPHAGOCYTIC SYNDROME; DIFFERENTIAL-DIAGNOSIS; SUPEROXIDE-DISMUTASE;
MURINE MACROPHAGES; INTERFERON-GAMMA; VIRULENCE FACTOR; IMMUNE-RESPONSE
AB Visceral leishmaniasis (VL) remains a major public health problem worldwide. This disease is highly associated with chronic inflammation and a lack of the cellular immune responses against Leishmania. It is important to identify major factors driving the successful establishment of the Leishmatzia infection to develop better tools for the disease control. Heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, and its role in VL has not been investigated. In this study, we evaluated the role of HO-1 in the infection by Leishmatzia infantum chagasi, the causative agent of VL cases in Brazil. We found that L. chagasi infection or lipophosphoglycan isolated from promastigotes triggered HO-1 production by murine macrophages. Interestingly, cobalt protoporphyrin IX, an HO-1 inductor, increased the parasite burden in both mouse and human-derived macrophages. Upon L. chagasi infection, macrophages from Hmox1 knockout mice presented significantly lower parasite loads when compared with those from wild-type mice. Furthermore, upregulation of HO-1 by cobalt protoporphyrin IX diminished the production of TNF-alpha and reactive oxygen species by infected murine macrophages and increased Cu/Zn superoxide dismutase expression in human monocytes. Finally, patients with VL presented higher systemic concentrations of HO-1 than healthy individuals, and this increase of HO-1 was reduced after antileishmanial treatment, suggesting that HO-1 is associated with disease susceptibility. Our data argue that HO-1 has a critical role in the L. chagasi infection and is strongly associated with the inflammatory imbalance during VL. Manipulation of HO-1 pathways during VL could serve as an adjunctive therapeutic approach. The Journal of Immunology, 2012, 188: 4460-4467.
C1 [Luz, Nivea F.; Araujo-Santos, Theo; Carvalho, Graziele Q.; Andrade, Daniela; Abanades, Daniel R.; Brodskyn, Claudia I.; Barral-Netto, Manoel; Barral, Aldina; Borges, Valeria M.] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, BR-40295001 Salvador, BA, Brazil.
[Luz, Nivea F.; Araujo-Santos, Theo; Carvalho, Graziele Q.; Andrade, Daniela; Abanades, Daniel R.; Brodskyn, Claudia I.; Barral-Netto, Manoel; Barral, Aldina; Borges, Valeria M.] Univ Fed Bahia, BR-40110060 Salvador, BA, Brazil.
[Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Feijo, Daniel F.; Bozza, Marcelo T.] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Imunol, BR-21941590 Rio De Janeiro, Brazil.
[Melo, Enaldo V.; Silva, Angela M.; Ameida, Roque P.] Univ Fed Sergipe, Univ Hosp, Dept Med, BR-49010390 Aracaju, Brazil.
[Brodskyn, Claudia I.; Barral-Netto, Manoel; Barral, Aldina; Ameida, Roque P.; Borges, Valeria M.] Inst Nacl Ciencia & Tecnol Invest Imunol, BR-40110100 Salvador, BA, Brazil.
[Soares, Rodrigo P.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil.
RP Borges, VM (reprint author), Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil.
EM vborges@bahia.fiocruz.br
RI Andrade, Bruno/J-9111-2012; Barral Netto, Manoel/B-3904-2009;
Imunologia, Inct/I-2124-2013; Araujo-Santos, Theo/F-9807-2014; Borges,
Valeria/G-2009-2014;
OI Borges, Valeria/0000-0002-2775-5409; Andrade, Bruno/0000-0001-6833-3811;
Barral Netto, Manoel/0000-0002-5823-7903; Araujo-Santos,
Theo/0000-0001-9861-6660; Farias Luz, Nivea/0000-0003-1958-7043
FU Fundacao de Amparo a Pesquisa do Estado da Bahia; Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq); Instituto Nacional de
Ciencia e Tecnologia de Investigacao em Imunologia; Coordenacao de
Aperfeicoamento de Pessoal de Nivel Superior; National Institute for
Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported by Fundacao de Amparo a Pesquisa do Estado da
Bahia, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
(CNPq), and Instituto Nacional de Ciencia e Tecnologia de Investigacao
em Imunologia. N.F.L., D.F.F. TA-S., and G.Q.C. are recipients of CNPq
fellowships. D.A. received a fellowship from Coordenacao de
Aperfeicoamento de Pessoal de Nivel Superior. C.I.B., R.P.S., M.B.-N.,
A.B., R.P.A., M.T.B., and V.M.B. are senior investigators from CNPq. The
work of B.B.A. is supported by the intramural research program of the
National Institute for Allergy and Infectious Diseases, National
Institutes of Health.
NR 67
TC 20
Z9 20
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
IS 9
BP 4460
EP 4467
DI 10.4049/jimmunol.1103072
PG 8
WC Immunology
SC Immunology
GA 932OH
UT WOS:000303299900039
PM 22461696
ER
PT J
AU Guerrero-Beltran, CE
Mukhopadhyay, P
Horvath, B
Rajesh, M
Tapia, E
Garcia-Torres, I
Pedraza-Chaverri, J
Pacher, P
AF Enrique Guerrero-Beltran, Carlos
Mukhopadhyay, Partha
Horvath, Bela
Rajesh, Mohanraj
Tapia, Edilia
Garcia-Torres, Itzhel
Pedraza-Chaverri, Jose
Pacher, Pal
TI Sulforaphane, a natural constituent of broccoli, prevents cell death and
inflammation in nephropathy
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Sulforaphane; Natural compound; Nephropathy; Inflammation; Cell death;
Cisplatin
ID ISCHEMIA-REPERFUSION INJURY; RAT-KIDNEY MITOCHONDRIA;
ACUTE-RENAL-FAILURE; P38 MAP KINASE; NF-KAPPA-B; CISPLATIN
NEPHROTOXICITY; OXIDATIVE STRESS; ISOTHIOCYANATE SULFORAPHANE;
ISCHEMIA/REPERFUSION INJURY; IN-VITRO
AB Cisplatin (cis-diamminedichloroplatinum II, CIS) is a potent and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited because of dose-dependent nephrotoxicity. Cell death and inflammation play a key role in the development and progression of CIS-induced nephropathy. Sulforaphane (SFN), a natural constituent of cruciferous vegetables such as broccoli, Brussels sprouts, etc., has been shown to exert various protective effects in models of tissue injury and cancer. In this study, we have investigated the role of prosurvival, cell death and inflammatory signaling pathways using a rodent model of CIS-induced nephropathy, and explored the effects of SFN on these processes. Cisplatin triggered marked activation of stress signaling pathways [p53, Jun N-terminal kinase (JNK), and p38-alpha mitogen-activated protein kinase (MAPK)] and promoted cell death in the kidneys (increased DNA fragmentation, caspases-3/7 activity, terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling), associated with attenuation of various prosurvival signaling pathways [e.g., extracellular signal-regulated kinase (ERK) and p38-beta MAPK]. Cisplatin also markedly enhanced inflammation in the kidneys [promoted NF-kappa B activation, increased expression of adhesion molecules ICAM and VCAM, enhanced tumor necrosis factor-alpha (TNF-alpha) levels and inflammatory cell infiltration]. These effects were significantly attenuated by pretreatment of rodents with SFN. Thus, the cisplatin-induced nephropathy is associated with activation of various cell death and proinflammatory pathways (p53. JNK, p38-alpha, TNF-alpha and NF-kappa B) and impairments of key prosurvival signaling mechanisms (ERK and p38-beta). SFN is able to prevent the CIS-induced renal injury by modulating these pathways, providing a novel approach for preventing this devastating complication of chemotherapy. Published by Elsevier Inc.
C1 [Enrique Guerrero-Beltran, Carlos; Mukhopadhyay, Partha; Horvath, Bela; Rajesh, Mohanraj; Pedraza-Chaverri, Jose; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Enrique Guerrero-Beltran, Carlos; Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Dept Biol, Fac Quim, Mexico City 04510, DF, Mexico.
[Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1089 Budapest, Hungary.
[Tapia, Edilia] Inst Nacl Cardiol, Dept Nefrol, Mexico City 04510, DF, Mexico.
[Garcia-Torres, Itzhel] Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04510, DF, Mexico.
RP Pedraza-Chaverri, J (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
EM pedraza@unam.mx; pacher@mail.nih.gov
RI MUKHOPADHYAY, PARTHA/G-3890-2010; Horvath, Bela/A-7368-2009; Pacher,
Pal/B-6378-2008;
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108; Guerrero-Beltran, Carlos
Enrique/0000-0002-5001-0093; Garcia, Itzhel/0000-0002-3018-060X
FU NIH/NIAAA; Consejo Nacional de Ciencia y Tecnologia (CONACYT) [129838];
Direccion General de Asuntos del Personal Academic (DGAPA) [201910];
Hungarian Research Scientific Fund (OTKA) fellowship [MB08-A 80238]
FX Grants, sponsors and funding sources: This work was supported by the
Intramural Research Program of NIH/NIAAA (to Pacher P), Consejo Nacional
de Ciencia y Tecnologia (CONACYT) 129838 and Direccion General de
Asuntos del Personal Academic (DGAPA) 201910 (to Pedraza-Chaverri J).
Dr. Horvath was supported by a Hungarian Research Scientific Fund (OTKA)
fellowship (MB08-A 80238). The study sponsors had no role in the study
design, in the collection, analysis and interpretation of data; in the
writing of the manuscript; and in the decision to submit the manuscript
for publication.
NR 53
TC 37
Z9 38
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD MAY
PY 2012
VL 23
IS 5
BP 494
EP 500
DI 10.1016/j.jnutbio.2011.02.004
PG 7
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 937ED
UT WOS:000303640900011
PM 21684138
ER
PT J
AU Kaufmann, P
AF Kaufmann, Petra
TI Clinical research for neuropathies
SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
LA English
DT Article
DE clinical research; clinical trials; data sharing; neuropathy; research
infrastructure
AB The National Institutes of Health (NIH) has a long-standing commitment to neuropathy research. From 20052009, the NIH has committed US $115 million each year. A collaborative effort between researchers and patients can accelerate the translation of pre-clinical discoveries into better treatments for neuropathy patients. Clinical trials are needed to test these new treatments, but they can only be implemented in a timely fashion if patients with neuropathies are willing to participate. This perspective focuses on the value of having various outlets for informing both the patients and the physicians about existing clinical research opportunities and on the potential benefit of establishing patient registries to help with trial recruitment. Once data have been collected, there is a need to broadly share the data in order to inform future trials, and a first step would be to harmonize data collection by using Common Data Elements (CDEs).
C1 Natl Inst Neurol Disorders & Stroke, Off Clin Res, NSC, Bethesda, MD 20892 USA.
RP Kaufmann, P (reprint author), Natl Inst Neurol Disorders & Stroke, Off Clin Res, NSC, 6001 Execut Blvd,Room 2216, Bethesda, MD 20892 USA.
EM petra.kaufman@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1085-9489
J9 J PERIPHER NERV SYST
JI J. Peripher. Nerv. Syst.
PD MAY
PY 2012
VL 17
SU 2
SI SI
BP 40
EP 42
DI 10.1111/j.1529-8027.2012.00394.x
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 934JU
UT WOS:000303441200008
PM 22548622
ER
PT J
AU Kristinsson, SY
Goldin, L
Turesson, I
Hultcrantz, M
Bjorkholm, M
Landgren, O
AF Kristinsson, S. Y.
Goldin, L.
Turesson, I.
Hultcrantz, M.
Bjorkholm, M.
Landgren, O.
TI Family history of venous thromboembolism is associated with increased
risk for thrombosis in multiple myeloma: a population-based study
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Letter
ID DEEP-VEIN THROMBOSIS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY;
PLUS DEXAMETHASONE; THALIDOMIDE; LENALIDOMIDE; PREVENTION; SWEDEN
C1 [Kristinsson, S. Y.; Hultcrantz, M.; Bjorkholm, M.] Karolinska Univ Hosp, Div Hematol, Dept Med, Solna, Sweden.
[Goldin, L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Turesson, I.] Skane Univ Hosp, Malmo, Sweden.
[Landgren, O.] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
[Kristinsson, S. Y.; Hultcrantz, M.; Bjorkholm, M.] Karolinska Inst, Stockholm, Sweden.
RP Kristinsson, SY (reprint author), Karolinska Univ Hosp, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Intramural NIH HHS
NR 21
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD MAY
PY 2012
VL 10
IS 5
BP 962
EP 964
DI 10.1111/j.1538-7836.2012.04676.x
PG 3
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 934KK
UT WOS:000303442800030
PM 22372994
ER
PT J
AU Lin, YH
Salem, N
Wells, EM
Zhou, WY
Loewke, JD
Brown, JA
Lands, WEM
Goldman, LR
Hibbeln, JR
AF Lin, Yu Hong
Salem, Norman, Jr.
Wells, Ellen M.
Zhou, Weiyin
Loewke, James D.
Brown, James A.
Lands, William E. M.
Goldman, Lynn R.
Hibbeln, Joseph R.
TI Automated High-Throughput Fatty Acid Analysis of Umbilical Cord Serum
and Application to an Epidemiological Study
SO LIPIDS
LA English
DT Article
DE Gas chromatography; Automation; Robot; Fatty acid; Transesterification
ID GAS-CHROMATOGRAPHY; CONTROLLED-TRIAL; BLOOD-SERUM; TRANSESTERIFICATION;
CHILDHOOD; FISH; AGE; CONSUMPTION; PREVENTION; FINGERTIP
AB Large population studies show that polyunsaturated fatty acids are important for human health, but determining relationships between the health benefits and the fatty acid content has been hampered by the unavailability of labor-effective high-throughput technologies. An automated high throughput fatty acid analysis was developed from a previous procedure based on direct transesterification including the automation of chemical procedures, data acquisition and automatic data processing. The method was validated and applied to umbilical cord serum samples in an epidemiological study. The method was linear in the range of 1-600 mu g/mL serum with r (2) a parts per thousand yen0.99. The within-run CV was < 5.4% for 23 fatty acids and a range of recoveries over three concentrations were 76-119% in a low-lipid matrix with the exception of 14:0. The fatty acid concentration as measured by the robotic method for human plasma was in good agreement with the Lepage & Roy method. The fatty acid profile in umbilical cord serum from American subjects (n = 287) showed an average of 38.0, 24.9, 32.0 and 4.6% of total fatty acids for saturates, monounsaturates, n-6 and n-3 polyunsaturates, respectively. This is the first report of a complete, validated, cost-effective, automated, high throughput fatty acid measurement method along with application to a population-based study. Automated fatty acid analysis coupled with automated data processing greatly facilitates the high throughput, 72 samples transesterified in 6 h, required for large population-based studies.
C1 [Lin, Yu Hong; Salem, Norman, Jr.; Zhou, Weiyin; Loewke, James D.; Brown, James A.; Lands, William E. M.; Hibbeln, Joseph R.] NIAAA, Sec Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Wells, Ellen M.] Case Western Reserve Univ, Sch Med, Dept Environm Hlth Sci, Cleveland, OH 44106 USA.
[Wells, Ellen M.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Goldman, Lynn R.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Lin, YH (reprint author), NIAAA, Sec Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA.
EM yulin@mail.nih.gov
OI Wells, Ellen/0000-0002-7293-1395
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health; National Oceanic and Atmospheric Administration
FX This research was supported, in part, by the Intramural Research Program
of the National Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health; and the National Oceanic and Atmospheric
Administration. Thanks to Dr. Shui-Lin Niu for helping with the
preparation of the low lipid serum, and Mr. Brian Brown for his
assistance with manuscript editing.
NR 34
TC 19
Z9 20
U1 2
U2 17
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0024-4201
EI 1558-9307
J9 LIPIDS
JI Lipids
PD MAY
PY 2012
VL 47
IS 5
BP 527
EP 539
DI 10.1007/s11745-012-3661-6
PG 13
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 933IP
UT WOS:000303354400009
PM 22430941
ER
PT J
AU Linguraru, MG
Pura, JA
Pamulapati, V
Summers, RM
AF Linguraru, Marius George
Pura, John A.
Pamulapati, Vivek
Summers, Ronald M.
TI Statistical 4D graphs for multi-organ abdominal segmentation from
multiphase CT
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Multiphase CT; 4D graph; Multi-organ segmentation; Enhancement; Shape
ID AUTOMATED SEGMENTATION; PROBABILISTIC ATLAS; LIVER SEGMENTATION; IMAGE
SEGMENTATION; SHAPE PRIORS; MR-IMAGES; CUTS; MODEL; CLASSIFICATION;
CONSTRUCTION
AB The interpretation of medical images benefits from anatomical and physiological priors to optimize computer-aided diagnosis applications. Diagnosis also relies on the comprehensive analysis of multiple organs and quantitative measures of soft tissue. An automated method optimized for medical image data is presented for the simultaneous segmentation of four abdominal organs from 4D CT data using graph cuts. Contrast-enhanced CT scans were obtained at two phases: non-contrast and portal venous. Intra-patient data were spatially normalized by non-linear registration. Then 4D convolution using population training information of contrast-enhanced liver, spleen and kidneys was applied to multiphase data to initialize the 4D graph and adapt to patient-specific data. CT enhancement information and constraints on shape, from Parzen windows, and location, from a probabilistic atlas, were input into a new formulation of a 4D graph. Comparative results demonstrate the effects of appearance, enhancement, shape and location on organ segmentation. All four abdominal organs were segmented robustly and accurately with volume overlaps over 93.6% and average surface distances below 1.1 mm. Published by Elsevier B.V.
C1 [Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Linguraru, Marius George; Pura, John A.; Pamulapati, Vivek; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Linguraru, MG (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM mlingura@cnmc.org; rms@nih.gov
FU National Institutes of Health, Clinical Center
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, Clinical Center. The authors would
like to thank Ananda S. Chowdhury, PhD, Jesse K. Sandberg, Visal Desai
and Javed Aman for helping with the data analysis.
NR 62
TC 43
Z9 45
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD MAY
PY 2012
VL 16
IS 4
BP 904
EP 914
DI 10.1016/j.media.2012.02.001
PG 11
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA 937EP
UT WOS:000303642100012
PM 22377657
ER
PT J
AU Roberts, WC
Taylor, MA
Shirani, J
AF Roberts, William C.
Taylor, Marc A.
Shirani, Jamshid
TI Cardiac Findings at Necropsy in Patients With Chronic Kidney Disease
Maintained on Chronic Hemodialysis
SO MEDICINE
LA English
DT Article
ID STAGE RENAL-DISEASE; LONG-TERM HEMODIALYSIS; ABDOMINAL AORTIC
CALCIFICATION; CARDIOVASCULAR-DISEASE; DIALYSIS PATIENTS; VASCULAR
CALCIFICATION; ALL-CAUSE; MAINTENANCE HEMODIALYSIS; CLINICAL
EPIDEMIOLOGY; MITRAL-VALVE
AB Studies of multiple hearts at necropsy are lacking in patients who have been on chronic hemodialysis for chronic kidney disease (CKD). We studied at necropsy 120 patients who had been treated with hemodialysis for more than 1 year (mean, 5.25 +/- 4.33 yr). Their ages ranged from 24 to 81 years (mean, 53 yr); 91 (76%) were men. Calcific deposits were present in the heart at necropsy in 74 (62%) patients: in the epicardial coronary arteries in all 74 (62%); in the mitral annular region in 52 (42%) patients, and in the aortic valve cusps in 42 (35%) patients. The frequency and quantity of the cardiac calcific deposits were significantly greater in the older compared with the younger patients, and in those with longer durations of hemodialysis compared with those with shorter durations. Despite the calcific deposits, which were sometimes huge, only 47 (39%) patients had 1 or more coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaques, apparently no patient had clinical evidence of mitral stenosis, and 9 patients had clinical evidence of aortic valve stenosis. Thus, we found that CKD treated with hemodialysis is a major producer of cardiac calcific deposits, some of which can be massive. Only a minority of the calcific deposits, however, appeared to lead to cardiac dysfunction or myocardial ischemia during life.
C1 [Roberts, William C.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX 75246 USA.
[Roberts, William C.; Taylor, Marc A.; Shirani, Jamshid] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, 3500 Gaston Ave,Suite H-030, Dallas, TX 75246 USA.
EM wc.roberts@baylorhealth.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD; Baylor Health Care System Foundation, Dallas, TX
FX This study was supported by the National Heart, Lung, and Blood
Institute, Intramural Program, National Institutes of Health, Bethesda,
MD; and the Baylor Health Care System Foundation, Dallas, TX.
NR 55
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD MAY
PY 2012
VL 91
IS 3
BP 165
EP 178
DI 10.1097/MD.0b013e318256e076
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 936QK
UT WOS:000303604900006
PM 22549132
ER
PT J
AU Wu, MX
Yu, KF
Liu, AY
Ma, TF
AF Wu, Mi-Xia
Yu, Kai-Fun
Liu, Aiyi
Ma, Tie-Feng
TI Simultaneous optimal estimation in linear mixed models
SO METRIKA
LA English
DT Article
DE Least squares estimator; Analysis of variance estimator; Minimum
variance unbiased estimator; Linear mixed model
ID VARIANCE
AB Simultaneous optimal estimation in linear mixed models is considered. A necessary and sufficient condition is presented for the least squares estimator of the fixed effects and the analysis of variance estimator of the variance components to be of uniformly minimum variance simultaneously in a general variance components model. That is, the matrix obtained by orthogonally projecting the covariance matrix onto the orthogonal complement space of the column space of the design matrix is symmetric, each eigenvalue of the matrix is a linear combinations of the variance components and the number of all distinct eigenvalues of the matrix is equal to the the number of the variance components. Under this condition, uniformly optimal unbiased tests and uniformly most accurate unbiased confidence intervals are constructed for the parameters of interest. A necessary and sufficient condition is also given for the equivalence of several common estimators of variance components. Two examples of their application are given.
C1 [Wu, Mi-Xia] Beijing Univ Technol, Coll Appl Sci, Beijing 100124, Peoples R China.
[Yu, Kai-Fun; Liu, Aiyi] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA.
[Ma, Tie-Feng] SW Univ Finance & Econ, Sch Stat, Chengdu 611130, Sichuan, Peoples R China.
RP Wu, MX (reprint author), Beijing Univ Technol, Coll Appl Sci, Beijing 100124, Peoples R China.
EM wumixia@bjut.edu.cn
OI Liu, Aiyi/0000-0002-6618-5082
FU National Natural Science Foundation of China [10801005, 11026214];
Natural Science Foundation of Beijing [1102010]; Scientific Research
Foundation for the Returned Overseas Chinese Scholars, State Education
Ministry; Training Programme Foundation for the Beijing Municipal
Excellent Talents [PYZZ090421001156]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX Wu's research is partially supported by National Natural Science
Foundation of China (10801005, 11026214), Natural Science Foundation of
Beijing (1102010), Scientific Research Foundation for the Returned
Overseas Chinese Scholars, State Education Ministry and Training
Programme Foundation for the Beijing Municipal Excellent Talents
(PYZZ090421001156). Research of A. Liu and K. F. Yu is supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health. The authors are grateful to the two referees for their detailed
suggestions which considerably improved the quality of the paper.
NR 22
TC 1
Z9 2
U1 0
U2 7
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0026-1335
J9 METRIKA
JI Metrika
PD MAY
PY 2012
VL 75
IS 4
BP 471
EP 489
DI 10.1007/s00184-010-0337-1
PG 19
WC Statistics & Probability
SC Mathematics
GA 935GZ
UT WOS:000303508400003
ER
PT J
AU Ebmeier, SE
Tan, IS
Clapham, KR
Ramamurthi, KS
AF Ebmeier, Sarah E.
Tan, Irene S.
Clapham, Katie Rose
Ramamurthi, Kumaran S.
TI Small proteins link coat and cortex assembly during sporulation in
Bacillus subtilis
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID SPORE COAT; SUBCELLULAR-LOCALIZATION; MORPHOGENETIC PROTEIN;
PEPTIDOGLYCAN SYNTHESIS; ASPOROGENOUS MUTANTS; TRANSCRIPTION FACTOR;
ENDOSPORE FORMATION; GENE; MEMBRANE; CLONING
AB Mature spores of the bacterium Bacillus subtilis are encased by two concentric shells: an inner shell (the cortex), made of peptidoglycan; and an outer proteinaceous shell (the coat), whose basement layer is anchored to the surface of the developing spore via a 26-amino-acid-long protein called SpoVM. During sporulation, initiation of cortex assembly depends on the successful initiation of coat assembly, but the mechanisms that co-ordinate the morphogenesis of both structures are largely unknown. Here, we describe a sporulation pathway involving SpoVM and a 37-amino-acid-long protein named CmpA that is encoded by a previously un-annotated gene and is expressed under control of two sporulation-specific transcription factors (sE and SpoIIID). CmpA localized to the surface of the developing spore and deletion of cmpA resulted in cells progressing through the sporulation programme more quickly. Overproduction of CmpA did not affect normal growth or cell division, but delayed entry into sporulation and abrogated cortex assembly. In those cells that had successfully initiated coat assembly, CmpA was removed by a post-translational mechanism, presumably in order to overcome the sporulation inhibition it imposed. We propose a model in which CmpA participates in a developmental checkpoint that ensures the proper orchestration of coat and cortex morphogenesis by repressing cortex assembly until coat assembly successfully initiates.
C1 [Ebmeier, Sarah E.; Tan, Irene S.; Clapham, Katie Rose; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tan, Irene S.] Johns Hopkins Univ, NIH, Grad Partnerships Program, Baltimore, MD 21218 USA.
RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank S. Gottesman, D. Popham, V. Lee and members of the laboratory
for comments on the manuscript; R. Losick for helpful discussion and
advice; N. Majdalani and A. Battesti for training; K. Nagashima of the
Electron Microscopy Laboratory (NCI Frederick) for assistance with
electron microscopy; and the anonymous reviewer who notified us about
the SpoIIID binding site upstream of cmpA. This work was funded by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 66
TC 15
Z9 15
U1 2
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD MAY
PY 2012
VL 84
IS 4
BP 682
EP 696
DI 10.1111/j.1365-2958.2012.08052.x
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 936MO
UT WOS:000303594700007
PM 22463703
ER
PT J
AU Morgan, RA
AF Morgan, Richard A.
TI Human Tumor Xenografts: The Good, the Bad, and the Ugly
SO MOLECULAR THERAPY
LA English
DT Editorial Material
ID MOUSE MODELS; NUDE-MOUSE; MICE; CANCER; CELLS; METASTASIS
C1 NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, Bldg 10,CRC Room 3-5940,10 Ctr Dr,MSC1201, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
NR 23
TC 8
Z9 8
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
IS 5
BP 882
EP 884
DI 10.1038/mt.2012.73
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YS
UT WOS:000303484300002
PM 22549804
ER
PT J
AU Kariko, K
Muramatsu, H
Keller, JM
Weissman, D
AF Kariko, Katalin
Muramatsu, Hiromi
Keller, Jason M.
Weissman, Drew
TI Increased Erythropoiesis in Mice Injected With Submicrogram Quantities
of Pseudouridine-containing mRNA Encoding Erythropoietin
SO MOLECULAR THERAPY
LA English
DT Article
ID RED-CELL APLASIA; GENE-THERAPY; ANTIERYTHROPOIETIN ANTIBODIES;
RECOMBINANT ERYTHROPOIETIN; NUCLEOSIDE MODIFICATIONS; AUTOIMMUNE ANEMIA;
VACCINATION TRIAL; T-CELLS; EXPRESSION; ACTIVATION
AB Advances in the optimization of in vitro-transcribed mRNA are bringing mRNA-mediated therapy closer to reality. In cultured cells, we recently achieved high levels of translation with high-performance liquid chromatography (HPLC)-purified, in vitro-transcribed mRNAs containing the modified nucleoside pseudouridine. Importantly, pseudouridine rendered the mRNA non-immunogenic. Here, using erythropoietin (EPO)-encoding mRNA complexed with TransIT-mRNA, we evaluated this new generation of mRNA in vivo. A single injection of 100 ng (0.005 mg/kg) mRNA elevated serum EPO levels in mice significantly by 6 hours and levels were maintained for 4 days. In comparison, mRNA containing uridine produced 10-100-fold lower levels of EPO lasting only 1 day. EPO translated from pseudouridine-mRNA was functional and caused a significant increase of both reticulocyte counts and hematocrits. As little as 1 0 ng mRNA doubled reticulocyte numbers. Weekly injection of 100 ng of EPO mRNA was sufficient to increase the hematocrit from 43 to 57%, which was maintained with continued treatment. Even when a large amount of pseudouridine-mRNA was injected, no inflammatory cytokines were detectable in plasma. Using macaques, we could also detect significantly-increased serum EPO levels following intraperitoneal injection of rhesus EPO mRNA. These results demonstrate that HPLC-purified, pseudouridine-containing mRNAs encoding therapeutic proteins have great potential for clinical applications.
C1 [Kariko, Katalin; Muramatsu, Hiromi] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.
[Keller, Jason M.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Weissman, Drew] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
RP Kariko, K (reprint author), Univ Penn, Dept Neurosurg, 36th & Hamilton Walk, Philadelphia, PA 19104 USA.
EM kariko@mail.med.upenn.edu
FU National Institutes of Health [R01NS029331, R42HL87688, R01AI50484,
R21DE019059]
FX We thank Houping Ni for technical assistance, Magdolna Sebestyen (Roche
Madison, Madison, WI) for advice on the macaque study, and Mark Lewis
and Bioqual, Inc, Rockville, MD for performing the macaque studies. This
work was supported by National Institutes of Health (grant number
R01NS029331 and R42HL87688 to K.K.; R01AI50484 and R21DE019059 to D.W.).
K.K. and D.W. have formed a small biotech company RNARx that receives
funding from the National Institutes of Health (R42HL87688) to explore
the use of nucleoside-modified mRNA for gene therapy.
NR 34
TC 63
Z9 65
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
IS 5
BP 948
EP 953
DI 10.1038/mt.2012.7
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YS
UT WOS:000303484300010
PM 22334017
ER
PT J
AU Neschadim, A
Wang, JCM
Sato, T
Fowler, DH
Lavie, A
Medin, JA
AF Neschadim, Anton
Wang, James C. M.
Sato, Takeya
Fowler, Daniel H.
Lavie, Arnon
Medin, Jeffrey A.
TI Cell Fate Control Gene Therapy Based on Engineered Variants of Human
Deoxycytidine Kinase
SO MOLECULAR THERAPY
LA English
DT Article
ID VIRUS-THYMIDINE KINASE; DONOR T-CELLS; SUICIDE GENE; THYMIDYLATE
SYNTHASE; GANCICLOVIR RESISTANCE; VARICELLA-ZOSTER; STRUCTURAL BASIS;
FUSION PROTEIN; SAFETY SWITCH; HOST-DISEASE
AB The safety of cell therapy applications can be enhanced by the introduction of Cell Fate Control (CFC) elements, which encode pharmacologically controlled cellular suicide switches. CFC Gene Therapy (CFCGT) offers the possibility of establishing control over gene-modified cells (GMCs) with regards to their proliferation, differentiation, or function. However, enzymes commonly employed in these approaches often possess poor kinetics and high immunogenicity. We describe a novel CFCGT system based on engineered variants of human deoxyCytidine Kinase (dCK) that overcomes limitations of current modalities. Mutants of dCK with rationally designed active sites that make them thymidine-activating were stably introduced into cells by recombinant lentiviral vectors (LVs). Transduced cells maintained growth kinetics and function. These dCK mutants efficiently activate bromovinyl-deoxyuridine (BVdU), L-deoxythymidine (LdT), and L-deoxyuridine (LdU), which are otherwise not toxic to wild-type cells. We show that mutant dCK-expressing Jurkat, Molt-4, and U87mg cells could be efficiently eliminated in vitro and in xenogeneic leukemia and tumor models in vivo. We also describe a fusion construct of the thymidine-activating dCK to the cytoplasmic tail-truncated LNGFR molecule and applications to in vivo eradication of primary human T cells. This novel CFCGT system offers unique plasticity with respect to the wide range of prodrugs it can potentiate, and can be used as a reliable safety switch in cell and gene therapy.
C1 [Medin, Jeffrey A.] Univ Hlth Network, Toronto, ON M5G 2M1, Canada.
[Neschadim, Anton; Medin, Jeffrey A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Wang, James C. M.; Medin, Jeffrey A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada.
[Sato, Takeya] Tohoku Univ, Sendai, Miyagi 980, Japan.
[Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Lavie, Arnon] Univ Illinois, Chicago, IL USA.
RP Medin, JA (reprint author), Univ Hlth Network, 67 Coll St,4th Floor,Room 406, Toronto, ON M5G 2M1, Canada.
EM jmedin@uhnres.utoronto.ca
RI Lavie, Arnon/H-4927-2012;
OI Neschadim, Anton/0000-0003-1750-9703
FU CIHR
FX The authors acknowledge Sean P. Devine (Department of Medical
Biophysics, University of Toronto, Toronto, ON, Canada), Matthew Scaife
(Department of Medical Biophysics, University of Toronto), and Orlay
Lopez-Perez (University Health Network) for their assistance with
methods development. Funding for A.N. was provided by the CIHR Training
Program in Regenerative Medicine (TPRM). The authors declared no
conflict of interest.
NR 51
TC 9
Z9 10
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
IS 5
BP 1002
EP 1013
DI 10.1038/mt.2011.298
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YS
UT WOS:000303484300016
PM 22273576
ER
PT J
AU Abate-Daga, D
Rosenberg, SA
Morgan, RA
AF Abate-Daga, Daniel
Rosenberg, Steven A.
Morgan, Richard A.
TI Analysis of Gene Expression in Adoptively Transferred TCR-Engineered
Lymphocytes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Abate-Daga, Daniel; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 190
BP S75
EP S75
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600191
ER
PT J
AU Barese, CN
Krouse, AE
Metzger, ME
Sellers, S
Spenser, D
Farrell, T
Di Stasi, AB
Donahue, RE
Brenner, MK
Dunbar, CE
AF Barese, Cecilia N.
Krouse, Allen E.
Metzger, Mark E.
Sellers, Stephanie
Spenser, David
Farrell, Tom
Di Stasi, Antonio B.
Donahue, Robert E.
Brenner, Malcom K.
Dunbar, Cynthia E.
TI Inducible Caspase 9 as Safety Switch in Gene Therapies Targeting
Hematopoietic Stem Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Barese, Cecilia N.; Krouse, Allen E.; Metzger, Mark E.; Sellers, Stephanie; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Di Stasi, Antonio B.; Brenner, Malcom K.] Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 218
BP S85
EP S86
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600219
ER
PT J
AU Barrett, JA
Weber, G
Gerdemann, U
Kerkar, S
Muranski, P
Hensel, NF
Leen, A
Melenhorst, JJ
Bollard, CM
AF Barrett, John A.
Weber, Gerrit
Gerdemann, Ulrike
Kerkar, Sid
Muranski, Pawel
Hensel, Nancy F.
Leen, Ann
Melenhorst, Jos J.
Bollard, Cath M.
TI Donor T Cells Specific for Multiple Leukemia Antigens for Adoptive
Immunotherapy of Myeloid Leukemias after Stem Cell Transplantation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Barrett, John A.; Weber, Gerrit; Kerkar, Sid; Muranski, Pawel; Hensel, Nancy F.; Melenhorst, Jos J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Gerdemann, Ulrike; Leen, Ann; Bollard, Cath M.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 532
BP S205
EP S205
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600532
ER
PT J
AU Bauer, TR
Tuschong, LM
Russell, DW
Hickstein, DD
AF Bauer, Thomas R., Jr.
Tuschong, Laura M.
Russell, David W.
Hickstein, Dennis D.
TI Efficacy and Safety of the Foamy Viral Vector Delta Phi MscvCD18 in
Long-Term Follow-Up (4-6 years) of Four Dogs with Canine Leukocyte
Adhesion Deficiency
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Bauer, Thomas R., Jr.; Tuschong, Laura M.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Russell, David W.] Univ Washington, Div Hematol, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 221
BP S87
EP S87
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600222
ER
PT J
AU Cecchini, S
Virag, T
Kotin, R
AF Cecchini, Sylvain
Virag, Tamas
Kotin, Robert
TI Reproducible and Scalable Production Processes of Recombinant
Adeno-Associated Virus Compatible with Current Good Manufacturing
Practice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Cecchini, Sylvain; Virag, Tamas; Kotin, Robert] NHLBI, Mol Virol & Gene Therapy Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 588
BP S228
EP S228
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600588
ER
PT J
AU Chandler, RJ
Venditti, CP
AF Chandler, Randy J.
Venditti, Charles P.
TI Demonstration of Pre-Clinical Efficacy of rAAV8 Gene Transfer as a
Treatment for Methylmalonic Acidemia Using a Vector Suitable for Human
Clinical Trials
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 145
BP S58
EP S58
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600146
ER
PT J
AU Choi, U
Koontz, S
Malech, HL
AF Choi, Uimook
Koontz, Sherry
Malech, Harry L.
TI Comparison of Different Internal Promoter Performance in the CL20 SIN
HIV Lentivector Used To Correct Human X-Linked Chronic Granulomatous
Disease as Evaluated Ex Vivo and in NSG Mice Transplanted with
Transduced Patient CD34+Stem Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Choi, Uimook; Koontz, Sherry; Malech, Harry L.] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 7
BP S3
EP S4
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600008
ER
PT J
AU Cruz, C
Micklethwaite, K
Savoldo, B
Ku, S
Krance, R
Diouf, O
Kamble, R
Kennedy-Nasser, A
Barrett, J
Shpall, E
Heslop, H
Rooney, C
Brenner, M
Bollard, C
Dotti, G
AF Cruz, Conrad
Micklethwaite, Kenneth
Savoldo, Barbara
Ku, Stephanie
Krance, Robert
Diouf, Oumar
Kamble, Rammurti
Kennedy-Nasser, Alana
Barrett, John
Shpall, Elizabeth
Heslop, Helen
Rooney, Cliona
Brenner, Malcolm
Bollard, Catherine
Dotti, Gianpietro
TI Infusion of CD19-Directed/Multivirus-Specific CTLs Post HSCT for B Cell
Malignancies
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Cruz, Conrad; Micklethwaite, Kenneth; Savoldo, Barbara; Ku, Stephanie; Krance, Robert; Diouf, Oumar; Kamble, Rammurti; Kennedy-Nasser, Alana; Heslop, Helen; Rooney, Cliona; Brenner, Malcolm; Bollard, Catherine; Dotti, Gianpietro] Texas Childrens Hosp, Baylor Coll Med, Methodist Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Barrett, John] NHLBI, NIH, Bethesda, MD 20892 USA.
[Shpall, Elizabeth] UT MD Anderson Canc Ctr, Houston, TX USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 536
BP S207
EP S207
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600536
ER
PT J
AU Donsante, A
Haddad, MR
Kaler, SG
AF Donsante, Anthony
Haddad, Marie Reine
Kaler, Stephen G.
TI Directed Evolution To Create Choroid Plexus-Permissive AAV Capsid
Variants: Toward Novel Clinical Management of Lysosomal Storage
Disorders
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Donsante, Anthony] NICHHD, Program Mol Med, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 591
BP S229
EP S229
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600591
ER
PT J
AU Haddad, MR
Zerfas, PM
Donsante, A
Kaler, SG
AF Haddad, Marie Reine
Zerfas, Patricia M.
Donsante, Anthony
Kaler, Stephen G.
TI In Utero Brain-Directed AAV5 Gene Therapy Results in Rapid, Robust, and
Specific Transduction of Choroid Plexus Epithelia: Implications for
Rescue of Prenatal Lethal Mouse Models of Neurometabolic Disease
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Haddad, Marie Reine; Donsante, Anthony; Kaler, Stephen G.] NICHHD, Program Mol Med, NIH, Bethesda, MD 20892 USA.
[Zerfas, Patricia M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 164
BP S66
EP S66
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600165
ER
PT J
AU Hunter, MJ
Zhao, HF
Tuschong, LM
Kapoor, V
Burkholder, TH
Persons, DA
Hickstein, DD
AF Hunter, Michael J.
Zhao, Huifen
Tuschong, Laura M.
Kapoor, Veena
Burkholder, Tanya H.
Persons, Derek A.
Hickstein, Dennis D.
TI Human Versus Murine Phosphoglycerate Kinase (PGK) Promoter/Enhancer in
Canine Leukocyte Adhesion Deficiency
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Hunter, Michael J.; Tuschong, Laura M.; Kapoor, Veena; Hickstein, Dennis D.] NCI, NIH, Bethesda, MD 20892 USA.
[Zhao, Huifen; Persons, Derek A.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA.
[Burkholder, Tanya H.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 141
BP S57
EP S57
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600142
ER
PT J
AU Ikawa, Y
Uchiyama, T
Jagadeesh, J
Candotti, F
AF Ikawa, Yasuhiro
Uchiyama, Toru
Jagadeesh, Jayashree
Candotti, Fabio
TI Comparison of Safety and Effectiveness between Gamma-Retroviral,
Lentiviral and Foamy Virus Gene Transfer Vectors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Ikawa, Yasuhiro; Uchiyama, Toru; Jagadeesh, Jayashree; Candotti, Fabio] NHGRI, GMBB, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 493
BP S191
EP S191
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600493
ER
PT J
AU Kouprina, N
AF Kouprina, Natalay
TI Human Artificial Chromosome (HAC) Vector with a Conditional Centromere
for Correction of Genetic Deficiencies in Human Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Kouprina, Natalay] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 124
BP S50
EP S51
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600125
ER
PT J
AU Lee, YM
Jun, HS
Pan, CJ
Lin, SR
Wilson, LH
Mansfield, BC
Chou, JY
AF Lee, Young Mok
Jun, Hyun Sik
Pan, Chi-Jiunn
Lin, Su Ru
Wilson, Lane H.
Mansfield, Brian C.
Chou, Janice Y.
TI Prevention of Hepatocellular Adenoma and Correction of Metabolic
Abnormalities in Murine Glycogen Storage Disease Type la by Gene Therapy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Lee, Young Mok; Jun, Hyun Sik; Pan, Chi-Jiunn; Lin, Su Ru; Wilson, Lane H.; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Bethesda, MD USA.
RI Jun, Hyun Sik/C-6799-2013
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 132
BP S53
EP S54
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600133
ER
PT J
AU Li, LN
Levy, JR
Yang, Y
Dimitriadis, EK
Garcia, L
Kotin, RM
AF Li, Lina
Levy, Justin R.
Yang, Yu
Dimitriadis, Emilios K.
Garcia, Luis
Kotin, Robert M.
TI Closed-Ended Linear Duplex AAV (celdAAV) DNA for Non-Viral Gene Transfer
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Li, Lina; Levy, Justin R.; Yang, Yu; Kotin, Robert M.] NHLBI, Mol Virol & Gene Therapy Lab, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
[Garcia, Luis] INSERM, U974, Inst Myol, Paris, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 613
BP S236
EP S236
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600611
ER
PT J
AU Mingozzi, F
Chen, YF
Zhou, SZ
Murphy, S
Mezger, M
Donahue, R
Wright, F
Dunbar, C
High, K
AF Mingozzi, Federico
Chen, Yifeng
Zhou, Shangzhen
Murphy, Samuel
Mezger, Mark
Donahue, Robert
Wright, Fraser
Dunbar, Cynthia
High, Katherine
TI Pharmacological Modulation of Humoral Immunity in a Non-Human Primate
Model of AAV Gene Transfer for Hemophilia B
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Mingozzi, Federico; Chen, Yifeng; Zhou, Shangzhen; Murphy, Samuel; Wright, Fraser; High, Katherine] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Chen, Yifeng; High, Katherine] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
[Mezger, Mark; Donahue, Robert; Dunbar, Cynthia] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 556
BP S215
EP S215
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600556
ER
PT J
AU Senac, JS
Sysol, JR
Venditti, CP
AF Senac, Julien S.
Sysol, Justin R.
Venditti, Charles P.
TI Hepatocyte Therapy for MUT Methylmalonic Acidemia
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Senac, Julien S.; Sysol, Justin R.; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 146
BP S59
EP S59
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600147
ER
PT J
AU Shaw, KL
Sokolic, R
Mishra, S
Geiger, S
Garabedian, E
de Oliveira, S
Carbonaro, DA
Muul, L
Silvin, C
Jagadeesh, J
Fu, PY
Crooks, GM
Moore, T
Candotti, F
Kohn, DB
AF Shaw, Kit L.
Sokolic, Robert
Mishra, Suparna
Geiger, Sabine
Garabedian, Elizabeth
de Oliveira, Satiro
Carbonaro, Denise A.
Muul, Linda
Silvin, Chris
Jagadeesh, Jayashree
Fu, Pei-Yu
Crooks, Gay M.
Moore, Theodore
Candotti, Fabio
Kohn, Donald B.
TI Update on the US Clinical Gene Therapy Trial for Adenosine Deaminase
Deficient Severe Combined Immune Deficiency (ADA-SCID)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Shaw, Kit L.; Mishra, Suparna; Geiger, Sabine; de Oliveira, Satiro; Carbonaro, Denise A.; Fu, Pei-Yu; Crooks, Gay M.; Moore, Theodore; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sokolic, Robert; Garabedian, Elizabeth; Muul, Linda; Silvin, Chris; Jagadeesh, Jayashree; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
RI Sokolic, Robert/I-6072-2012
NR 0
TC 0
Z9 0
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 53
BP S22
EP S22
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600054
ER
PT J
AU Sweeney, CL
Merling, RK
Choi, U
Wang, HM
Holland, SM
Malech, HL
AF Sweeney, Colin L.
Merling, Randall K.
Choi, Uimook
Wang, Hongmei
Holland, Steven M.
Malech, Harry L.
TI Extreme Skewing of X-Chromosome Inactivation in Female Carriers of X-CGD
Can Be Reversed during iPSC Reprogramming To Restore Neutrophil Function
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Sweeney, Colin L.; Merling, Randall K.; Choi, Uimook; Wang, Hongmei; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 566
BP S219
EP S220
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600566
ER
PT J
AU Templeton, NS
Ko, E
Burgess, K
Phalon, C
Chen, L
Roberts, DD
Jay, CM
Brunicardi, FC
Maples, PB
Senzer, N
Nemunaitis, J
AF Templeton, Nancy S.
Ko, Eunhwa
Burgess, Kevin
Phalon, Connor
Chen, Li
Roberts, David D.
Jay, Chris M.
Brunicardi, F. C.
Maples, Phillip B.
Senzer, Neil
Nemunaitis, John
TI Recent Advances Using Small Molecule Targeting for Bilamellar
Invaginated Vesicle (BIV) Delivery
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Templeton, Nancy S.; Phalon, Connor; Chen, Li; Jay, Chris M.; Maples, Phillip B.; Senzer, Neil; Nemunaitis, John] Gradalis Inc, Dallas, TX USA.
[Ko, Eunhwa; Burgess, Kevin] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
[Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Brunicardi, F. C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Senzer, Neil; Nemunaitis, John] Mary Crowley Canc Res Ctr, Dallas, TX USA.
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 398
BP S155
EP S156
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600399
ER
PT J
AU Uchida, N
Tisdale, JF
AF Uchida, Naoya
Tisdale, John F.
TI A Hematopoietic Stem Cell Expansion Medium Increased Transduction
Efficiency for Human CD34+Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Uchida, Naoya; Tisdale, John F.] NHLBI, MCHB, NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 494
BP S191
EP S192
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600494
ER
PT J
AU Wellman, JA
Mingozzi, F
Ozelo, MC
Arruda, V
Podsakoff, G
Chen, YF
Konkle, BA
Blatt, PM
Hoots, K
Raffini, LJ
Rasko, J
Ragni, MV
High, KA
AF Wellman, Jennifer A.
Mingozzi, Federico
Ozelo, Margareth C.
Arruda, Valder
Podsakoff, Greg
Chen, Yifeng
Konkle, Barbara A.
Blatt, Philip M.
Hoots, Keith
Raffini, Leslie J.
Rasko, John
Ragni, Margaret V.
High, Katherine A.
TI Results from the Long-Term Follow-Up of Severe Hemophilia B Subjects
Previously Enrolled in a Clinical Study of AAV2-FIX Gene Transfer to the
Liver
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Wellman, Jennifer A.; Mingozzi, Federico; Arruda, Valder; Podsakoff, Greg; Chen, Yifeng; High, Katherine A.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA USA.
[Ozelo, Margareth C.] Univ Estadual Campinas, Campinas, Brazil.
[Konkle, Barbara A.] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Blatt, Philip M.] Duke Univ, Durham, NC USA.
[Hoots, Keith] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rasko, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
[Ragni, Margaret V.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[High, Katherine A.] HHMI, Chevy Chase, MD USA.
RI Ozelo, Margareth/K-5819-2012
OI Ozelo, Margareth/0000-0001-5938-0675
NR 0
TC 3
Z9 3
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 69
BP S28
EP S29
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600070
ER
PT J
AU Yang, SC
Karne, NK
Goff, SL
Black, MA
Xu, H
Bischof, D
Cornetta, K
Rosenberg, SA
Morgan, RA
Feldman, SA
AF Yang, Shicheng
Karne, Neel K.
Goff, Stephanie L.
Black, Mary A.
Xu, Hui
Bischof, Daniela
Cornetta, Kenneth
Rosenberg, Steven A.
Morgan, Richard A.
Feldman, Steven A.
TI A Simple and Effective Method To Generate Lentiviral Vectors for Ex Vivo
Gene Delivery to Mature Human Peripheral Blood Lymphocytes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Yang, Shicheng; Karne, Neel K.; Goff, Stephanie L.; Black, Mary A.; Xu, Hui; Rosenberg, Steven A.; Morgan, Richard A.; Feldman, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Yang, Shicheng] Duke Univ, Dept Surg, Durham, NC USA.
[Karne, Neel K.] SUNY Upstate Med Univ, Dept Surg Gen Surg, Syracuse, NY USA.
[Goff, Stephanie L.] Columbia Univ, Dept Surg, New York, NY USA.
[Bischof, Daniela; Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA.
[Cornetta, Kenneth] Indiana Univ Sch Med, Dept Immunol & Microbiol, Indianapolis, IN USA.
[Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 753
BP S290
EP S290
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600748
ER
PT J
AU Zhang, JY
Thorgeirsson, SS
Jessup, JM
AF Zhang, Jingyu
Thorgeirsson, Snorri S.
Jessup, J. Milburn
TI Allele-Specific Inhibition of Nanog Family Members Inhibits
Three-Dimensional (3-D) Growth of Human Colorectal Carcinoma (CRC) In
Vitro
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Zhang, Jingyu; Thorgeirsson, Snorri S.; Jessup, J. Milburn] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 473
BP S184
EP S184
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600474
ER
PT J
AU Zhang, L
Zheng, ZL
Yu, ZY
Dudley, ME
Falgout, JA
Restifo, NP
Rosenberg, SA
Morgan, RA
AF Zhang, Ling
Zheng, Zhili
Yu, Zhiya
Dudley, Mark E.
Falgout, Jeffery A.
Restifo, Nicholas P.
Rosenberg, Steven A.
Morgan, Richard A.
TI TGF-beta as a Modifier of Response to Adoptive Cell Therapy for
Melanoma: Enhanced Tumor Treatment in Animal Models and a Highly
Significant Correlation between Clinical Response and TGF-beta Genotypes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Zhang, Ling; Zheng, Zhili; Yu, Zhiya; Dudley, Mark E.; Falgout, Jeffery A.; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 534
BP S206
EP S206
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600534
ER
PT J
AU Zou, JZ
Sweeney, CL
Malech, HL
Cheng, LZ
AF Zou, Jizhong
Sweeney, Colin L.
Malech, Harry L.
Cheng, Linzhao
TI Generation of Integration-Free iPSCs from an X-CGD Patient's Blood Cells
as Clinically Relevant Target for Gene-Repair Using Designer ZFN or
TALEN
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Zou, Jizhong; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
[Sweeney, Colin L.; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 280
BP S110
EP S111
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600281
ER
PT J
AU Clarke, L
Zheng-Bradley, X
Smith, R
Kulesha, E
Xiao, CL
Toneva, I
Vaughan, B
Preuss, D
Leinonen, R
Shumway, M
Sherry, S
Flicek, P
AF Clarke, Laura
Zheng-Bradley, Xiangqun
Smith, Richard
Kulesha, Eugene
Xiao, Chunlin
Toneva, Iliana
Vaughan, Brendan
Preuss, Don
Leinonen, Rasko
Shumway, Martin
Sherry, Stephen
Flicek, Paul
CA 1000 Genomes Project Consortium
TI The 1000 Genomes Project: data management and community access
SO NATURE METHODS
LA English
DT Article
ID VARIANTS; FORMAT
AB The 1000 Genomes Project was launched as one of the largest distributed data collection and analysis projects ever undertaken in biology. In addition to the primary scientific goals of creating both a deep catalog of human genetic variation and extensive methods to accurately discover and characterize variation using new sequencing technologies, the project makes all of its data publicly available. Members of the project data coordination center have developed and deployed several tools to enable widespread data access.
C1 [Clarke, Laura; Zheng-Bradley, Xiangqun; Smith, Richard; Kulesha, Eugene; Toneva, Iliana; Vaughan, Brendan; Leinonen, Rasko; Flicek, Paul] European Bioinformat Inst, Cambridge, England.
[Xiao, Chunlin; Preuss, Don; Shumway, Martin; Sherry, Stephen] US Natl Inst Hlth, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD USA.
RP Flicek, P (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge, England.
EM flicek@ebi.ac.uk
RI Khurana, Ekta/C-4933-2013; Ding, Jun/G-3918-2011; Altshuler,
David/A-4476-2009; Rosenstiel, Philip/A-5137-2009; Ye, Kai/B-3640-2012;
Myers, Simon/A-6792-2015; Browning, Brian/A-1178-2010; Dahl,
Andreas/E-3783-2017;
OI Hinrichs, Angie/0000-0002-1697-1130; Keane, Thomas/0000-0001-7532-6898;
Zheng Bradley, Xiangqun/0000-0002-9324-2708; Sebat,
Jonathan/0000-0002-9087-526X; Leinonen, Rasko/0000-0002-2639-7187;
Haraksingh, Rajini/0000-0002-6644-8874; Vaughan,
Brendan/0000-0002-2199-1267; Herrero, Javier/0000-0001-7313-717X;
Clarke, Laura/0000-0002-5989-6898; Flicek, Paul/0000-0002-3897-7955;
McLaren, William/0000-0001-6218-1116; Walter,
Klaudia/0000-0003-4448-0301; Keenan, Stephen/0000-0002-9141-7690;
Altshuler, David/0000-0002-7250-4107; Rosenstiel,
Philip/0000-0002-9692-8828; Myers, Simon/0000-0002-2585-9626; Browning,
Brian/0000-0001-6454-6633; Dahl, Andreas/0000-0002-2668-8371; Kulesha,
Eugene/0000-0002-4285-6232; Zalunin, Vadim/0000-0002-7722-1958;
Radhakrishnan, Rajesh/0000-0001-7170-699X
FU Wellcome Trust [WT085532]; European Molecular Biology Laboratory; US
National Institutes of Health National Library of Medicine
FX For early work and support to the DCC, we thank Z. Iqbal, H. Khouri, F.
Cunningham, Y. Chen, W. McLaren, V. Zalunin, R. Radhakrishnan, D.
Smirnov, J. Paschall, Z. Belaia, R. Sanders, C. O'Sullivan, S. Keenan,
G. Ritchie and G. Cochrane. For maintenance of the EBI computer
infrastructure, we acknowledge J. Barker, V. Silventoinen, G. Kellman
and P. Jokinen. Funding support at the EBI is provided by the Wellcome
Trust (grant WT085532) and the European Molecular Biology Laboratory.
This research was supported in part by the Intramural Research Program
of the US National Institutes of Health National Library of Medicine.
NR 16
TC 92
Z9 96
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAY
PY 2012
VL 9
IS 5
BP 1
EP 4
DI 10.1038/NMETH.1974
PG 4
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 935TU
UT WOS:000303544800021
PM 22543379
ER
PT J
AU Pajevic, S
Plenz, D
AF Pajevic, Sinisa
Plenz, Dietmar
TI The organization of strong links in complex networks
SO NATURE PHYSICS
LA English
DT Article
ID SMALL-WORLD NETWORKS; NEURONAL AVALANCHES; TOPOLOGY; WEAK
AB Many complex systems reveal a small-world topology, which allows simultaneously local and global efficiency in the interaction between system constituents. Here, we report the results of a comprehensive study that investigates the relation between the clustering properties in such small-world systems and the strength of interactions between its constituents, quantified by the link weight. For brain, gene, social and language networks, we find a local integrative weight organization in which strong links preferentially occur between nodes with overlapping neighbourhoods; we relate this to global robustness of the clustering to removal of the weakest links. Furthermore, we identify local learning rules that establish integrative networks and improve network traffic in response to past traffic failures. Our findings identify a general organization for complex systems that strikes a balance between efficient local and global communication in their strong interactions, while allowing for robust, exploratory development of weak interactions.
C1 [Pajevic, Sinisa] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Plenz, Dietmar] NIH, Sect Crit Brain Dynam, Lab Syst Neurosci, Bethesda, MD 20892 USA.
RP Pajevic, S (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM pajevic@nih.gov
FU NIH of the NIMH; DCB/CIT
FX We thank M. Boguna and members of the Section on Critical Brain
Dynamics, NIMH, NIH, for constructive comments during this work. We also
thank S. Yu for providing some of the monkey data and J. Alstott for
Matlab implementation of one of the social network models. This work was
supported by the NIH Intramural Research Program of the NIMH and the
DCB/CIT.
NR 41
TC 17
Z9 19
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1745-2473
J9 NAT PHYS
JI Nat. Phys.
PD MAY
PY 2012
VL 8
IS 5
BP 429
EP 436
DI 10.1038/NPHYS2257
PG 8
WC Physics, Multidisciplinary
SC Physics
GA 936OF
UT WOS:000303599200025
ER
PT J
AU Maecker, HT
McCoy, JP
Nussenblatt, R
AF Maecker, Holden T.
McCoy, J. Philip
Nussenblatt, Robert
TI Reducing variability in flow cytometry
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Letter
C1 [Maecker, Holden T.] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
[McCoy, J. Philip; Nussenblatt, Robert] Natl Inst Hlth, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[McCoy, J. Philip] Natl Heart Lung & Blood Inst, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Nussenblatt, Robert] NEI, Natl Inst Hlth, Bethesda, MD 20893 USA.
RP Maecker, HT (reprint author), Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
EM maecker@stanford.edu
NR 4
TC 3
Z9 3
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD MAY
PY 2012
VL 12
IS 5
DI 10.1038/nri3158-c2
PG 1
WC Immunology
SC Immunology
GA 933ET
UT WOS:000303343300015
ER
PT J
AU Boyden, SE
Mahoney, LJ
Kawahara, G
Myers, JA
Mitsuhashi, S
Estrella, EA
Duncan, AR
Dey, F
DeChene, ET
Blasko-Goehringer, JM
Bonnemann, CG
Darras, BT
Mendell, JR
Lidov, HGW
Nishino, I
Beggs, AH
Kunkel, LM
Kang, PB
AF Boyden, Steven E.
Mahoney, Lane J.
Kawahara, Genri
Myers, Jennifer A.
Mitsuhashi, Satomi
Estrella, Elicia A.
Duncan, Anna R.
Dey, Friederike
DeChene, Elizabeth T.
Blasko-Goehringer, Jessica M.
Boennemann, Carsten G.
Darras, Basil T.
Mendell, Jerry R.
Lidov, Hart G. W.
Nishino, Ichizo
Beggs, Alan H.
Kunkel, Louis M.
Kang, Peter B.
TI Mutations in the satellite cell gene MEGF10 cause a recessive congenital
myopathy with minicores
SO NEUROGENETICS
LA English
DT Article
DE MEGF10; Whole genome sequencing; Linkage analysis; Congenital myopathy;
Satellite cells; Cleft palate
ID SKELETAL-MUSCLE REGENERATION; FIBER-TYPE DISPROPORTION;
MUSCULAR-DYSTROPHY; ZEBRAFISH; DISEASE; PROTEIN; CED-1; IDENTIFICATION;
SPECIFICATION; ORGANIZATION
AB We ascertained a nuclear family in which three of four siblings were affected with an unclassified autosomal recessive myopathy characterized by severe weakness, respiratory impairment, scoliosis, joint contractures, and an unusual combination of dystrophic and myopathic features on muscle biopsy. Whole genome sequence from one affected subject was filtered using linkage data and variant databases. A single gene, MEGF10, contained nonsynonymous mutations that co-segregated with the phenotype. Affected subjects were compound heterozygous for missense mutations c.976T > C (p.C326R) and c.2320T > C (p.C774R). Screening the MEGF10 open reading frame in 190 patients with genetically unexplained myopathies revealed a heterozygous mutation, c.211C > T (p.R71W), in one additional subject with a similar clinical and histological presentation as the discovery family. All three mutations were absent from at least 645 genotyped unaffected control subjects. MEGF10 contains 17 atypical epidermal growth factor-like domains, each of which contains eight cysteine residues that likely form disulfide bonds. Both the p.C326R and p.C774R mutations alter one of these residues, which are completely conserved in vertebrates. Previous work showed that murine Megf10 is required for preserving the undifferentiated, proliferative potential of satellite cells, myogenic precursors that regenerate skeletal muscle in response to injury or disease. Here, knockdown of megf10 in zebrafish by four different morpholinos resulted in abnormal phenotypes including unhatched eggs, curved tails, impaired motility, and disorganized muscle tissue, corroborating the pathogenicity of the human mutations. Our data establish the importance of MEGF10 in human skeletal muscle and suggest satellite cell dysfunction as a novel myopathic mechanism.
C1 [Darras, Basil T.; Kang, Peter B.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Boyden, Steven E.; Kunkel, Louis M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Boyden, Steven E.; Mahoney, Lane J.; Kawahara, Genri; Myers, Jennifer A.; Mitsuhashi, Satomi; Estrella, Elicia A.; Duncan, Anna R.; Dey, Friederike; DeChene, Elizabeth T.; Blasko-Goehringer, Jessica M.; Lidov, Hart G. W.; Beggs, Alan H.; Kunkel, Louis M.; Kang, Peter B.] Childrens Hosp, Div Genet, Program Genom, Boston, MA 02115 USA.
[Boyden, Steven E.; Mahoney, Lane J.; Kawahara, Genri; Myers, Jennifer A.; Mitsuhashi, Satomi; Estrella, Elicia A.; Duncan, Anna R.; Dey, Friederike; DeChene, Elizabeth T.; Blasko-Goehringer, Jessica M.; Lidov, Hart G. W.; Beggs, Alan H.; Kunkel, Louis M.; Kang, Peter B.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
[Mitsuhashi, Satomi; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, Tokyo, Japan.
[Boennemann, Carsten G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Mendell, Jerry R.] Nationwide Childrens Hosp, Ctr Gene Therapy Res Inst, Columbus, OH USA.
[Lidov, Hart G. W.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Beggs, Alan H.; Kunkel, Louis M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Kang, PB (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA.
EM peter.kang@childrens.harvard.edu
OI Beggs, Alan/0000-0001-8818-0568; Nishino, Ichizo/0000-0001-9452-112X
FU NIH [K08 NS048180, R01 AR044345, P50 NS40828]; Genise Goldenson Fund;
Children's Hospital Boston; Muscular Dystrophy Association [186796,
201302]; Bernard F. and Alva B. Gimbel Foundation; Lee and Penny
Anderson Family Foundation; Professor-Dr.Adolf-Schmidtmann-Stiftung; NIH
through the Intellectual and Developmental Disabilities Research Center
[P30 HD18655]
FX The authors thank the patients and their families for their
participation in this study, as well as Hal Schneider, Laura Moody,
Susan Kim, Sachiko Kajino, Kanako Goto, and Yukiko Hayashi for technical
assistance, Michael Lawlor and Pankaj Agrawal for helpful discussions,
Fedik Rahimov for critical reading of the manuscript, and Timothy Yu and
Christopher Walsh for contribution of control genome sequence data. This
work was supported by NIH K08 NS048180 (PBK), the Genise Goldenson Fund
(PBK), a Children's Hospital Boston Pilot Grant (PBK), Muscular
Dystrophy Association Research Grants 186796 (PBK) and 201302 (AHB), the
Bernard F. and Alva B. Gimbel Foundation (LMK), NIH R01 AR044345 (AHB),
the Lee and Penny Anderson Family Foundation (AHB), and the
Professor-Dr.-Adolf-Schmidtmann-Stiftung (FD). Microarray genotyping and
Sanger DNA sequencing experiments were performed in the Molecular
Genetics Core Facility at Children's Hospital Boston, supported by NIH
P30 HD18655 through the Intellectual and Developmental Disabilities
Research Center and NIH P50 NS40828 through the Neuromuscular Disease
Project. Electron microscopy was performed at the Harvard Medical School
EM Core Facility with the assistance of Maria Ericsson, Louise Trakimas,
and Elizabeth Benecchi.
NR 48
TC 18
Z9 20
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
J9 NEUROGENETICS
JI Neurogenetics
PD MAY
PY 2012
VL 13
IS 2
BP 115
EP 124
DI 10.1007/s10048-012-0315-z
PG 10
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA 933ZY
UT WOS:000303408600002
PM 22371254
ER
PT J
AU Callacondo, D
Garcia, HH
Gonzales, I
Escalante, D
Nash, TE
AF Callacondo, D.
Garcia, H. H.
Gonzales, I.
Escalante, D.
Nash, T. E.
CA Cysticercosis Working Grp Peru
TI High frequency of spinal involvement in patients with basal subarachnoid
neurocysticercosis
SO NEUROLOGY
LA English
DT Article
ID EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; FOLLOW-UP; CYSTICERCOSIS; DISEASE;
HYDROCEPHALUS; THERAPY
AB Objective: To determine the frequency of spinal neurocysticercosis (NCC) in patients with basal subarachnoid NCC compared with that in individuals with viable limited intraparenchymal NCC (<= 20 live cysts in the brain).
Methods: We performed a prospective observational case-control study of patients with NCC involving the basal cisterns or patients with only limited intraparenchymal NCC. All patients underwent MRI examinations of the brain and the entire spinal cord to assess spinal involvement.
Results: Twenty-seven patients with limited intraparenchymal NCC, and 28 patients with basal subarachnoid NCC were included in the study. Spinal involvement was found in 17 patients with basal subarachnoid NCC and in only one patient with limited intraparenchymal NCC (odds ratio 40.18, 95% confidence interval 4.74-340.31; p < 0.0001). All patients had extramedullary (intradural) spinal NCC, and the lumbosacral region was the most frequently involved (89%). Patients with extensive spinal NCC more frequently had ventriculoperitoneal shunt placement (7 of 7 vs 3 of 11; p = 0.004) and tended to have a longer duration of neurologic symptoms than those with regional involvement (72 months vs 24 months; p = 0.062).
Conclusions: The spinal subarachnoid space is commonly involved in patients with basal subarachnoid NCC, compared with those with only intraparenchymal brain cysts. Spinal cord involvement probably explains serious late complications including chronic meningitis and gait disorders that were described before the introduction of antiparasitic therapy. MRI of the spine should be performed in basal subarachnoid disease to document spinal involvement, prevent complications, and monitor for recurrent disease. Neurology (R) 2012;78:1394-1400
C1 [Nash, T. E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Callacondo, D.] Univ Peruana Cayetano Heredia, Labs Invest & Desarrollo, Lima, Peru.
[Callacondo, D.; Garcia, H. H.] Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru.
[Garcia, H. H.] Univ Peruana Cayetano Heredia, Ctr Global Hlth Tumbes, Lima, Peru.
[Garcia, H. H.; Gonzales, I.] Inst Nacl Ciencias Neurol, Dept Transmissible Dis, Cysticercosis Unit, Lima, Peru.
[Escalante, D.] RESOCENTRO, Lima, Peru.
RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
EM tnash@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH; Fogarty
International Center/NIH [D43 TW001140]
FX Supported in part by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, NIH, and by Fogarty
International Center/NIH (Training Grant D43 TW001140). H.H.G. is now a
Wellcome Trust International Senior Research Fellow.
NR 28
TC 19
Z9 19
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAY
PY 2012
VL 78
IS 18
BP 1394
EP 1400
DI 10.1212/WNL.0b013e318253d641
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 935DB
UT WOS:000303498000009
PM 22517102
ER
PT J
AU Bergman, HE
Hunt, YM
Augustson, E
AF Bergman, Hannah E.
Hunt, Yvonne M.
Augustson, Erik
TI Smokeless Tobacco Use in the United States Military: A Systematic Review
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Review
ID CARDIOVASCULAR-DISEASE; SMOKING-CESSATION; ORAL LEUKOPLAKIA;
ACTIVE-DUTY; AIR-FORCE; DUAL-USE; PERSONNEL; POPULATION; RECRUITS;
PREVALENCE
AB Smokeless tobacco (ST) use represents an important target for intervention in the U.S. military population because it impairs "military readiness" and harms the health of the military. This paper aims to provide a systematic review of ST studies conducted in the U.S. military population in order to assess the content of existing ST research in this population, provide estimates of prevalence and clinically relevant use patterns, and discuss how these findings might be used to guide future ST research among this population.
We reviewed articles published through December 2010 using PubMed and PsycINFO databases, Google Scholar, and any relevant articles' reference lists. Inclusion criteria included focus on a U.S. military sample, English language, measured tobacco use, and ST prevalence was reported or could be calculated. To the extent possible, each article was coded for demographics, socioeconomic status, prevalence, amount, frequency, and length of use, and quit intentions/attempts.
Thirty-nine articles met criteria for inclusion. Less than half focused primarily on ST use among military personnel. The remaining studies measured ST use in the context of other behaviors. Findings related to clinically relevant behaviors included a need for more cohort and intervention studies, a better understanding of ST use in combination with cigarettes (i.e., concurrent use), and identifying risk factors for ST initiation and use.
ST use is prevalent among military personnel, as is concurrent use of cigarettes and ST. We provide a number of recommendations to guide future research in this important, yet understudied, area.
C1 [Bergman, Hannah E.; Hunt, Yvonne M.; Augustson, Erik] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Bergman, HE (reprint author), Case Western Reserve Univ, Dept Psychol Sci, Psychol Program, 11220 Belleflower Rd,Mather Mem 109, Cleveland, OH 44106 USA.
EM hannah.bergman87@gmail.com
FU NCI, National Institutes of Health
FX The corresponding author was funded as a Cancer Research Training Award
Fellow at the NCI, National Institutes of Health, from September 2009 to
August 2011.
NR 56
TC 1
Z9 1
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD MAY
PY 2012
VL 14
IS 5
BP 507
EP 515
DI 10.1093/ntr/ntr216
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 933BS
UT WOS:000303334800001
PM 22123789
ER
PT J
AU Huskins, WC
Sullivan, CD
Wang, J
Aitken, M
Alexander, SR
Epstein, LG
Hoberman, A
Neufeld, E
Philipps, A
Shanley, TP
Szilagyi, P
Purucker, M
Barkin, SL
AF Huskins, W. Charles
Sullivan, Clare D.
Wang, Janey
Aitken, Mary
Alexander, Steven R.
Epstein, Leon G.
Hoberman, Alejandro
Neufeld, Ellis
Philipps, Anthony
Shanley, Thomas P.
Szilagyi, Peter
Purucker, Mary
Barkin, Shari L.
TI Tracking the impact of the National Institutes of Health Clinical and
Translational Science Awards on child health research: developing and
evaluating a measurement strategy
SO PEDIATRIC RESEARCH
LA English
DT Article
ID SUPPORT
C1 [Huskins, W. Charles] Mayo Clin, Div Pediat Infect Dis, Rochester, MN 55905 USA.
[Sullivan, Clare D.; Wang, Janey] Vanderbilt Inst Clin & Translat Res, Nashville, TN USA.
[Aitken, Mary] Arkansas Childrens Hosp Res Inst, Little Rock, AR USA.
[Alexander, Steven R.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Epstein, Leon G.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Hoberman, Alejandro] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
[Neufeld, Ellis] Childrens Hosp, Boston, MA 02115 USA.
[Neufeld, Ellis] Harvard Univ, Sch Med, Boston, MA USA.
[Philipps, Anthony] Univ Calif Davis, Dept Pediat, Sch Med, Sacramento, CA 95817 USA.
[Shanley, Thomas P.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Szilagyi, Peter] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Purucker, Mary] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA.
[Barkin, Shari L.] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN USA.
RP Huskins, WC (reprint author), Mayo Clin, Div Pediat Infect Dis, Rochester, MN 55905 USA.
EM huskins.charles@mayo.edu
OI Huskins, W. Charles/0000-0002-9989-175X
FU National Institutes of Health (NIH)/National Center for Research
Resources [UL1 RR024150, UL1 RR024975, UL1 RR029884, UL1 RR025744, UL1
RR025741, UL1 RR024153, UL1 RR025758, UL1 RR024146, UL1 RR024986, UL1
RR024160]
FX This publication was supported by National Institutes of Health
(NIH)/National Center for Research Resources Clinical and Translational
Science Award grant nos. UL1 RR024150 (Mayo Center for Translational
Science Activities, Mayo Clinic); UL1 RR024975 (Vanderbilt Institute for
Clinical and Translational Research, Vanderbilt University); UL1
RR029884 (Arkansas Center for Clinical and Translational Research,
University of Arkansas for Medical Sciences); UL1 RR025744 (The Stanford
Center for Clinical and Translational Education and Research, Stanford
University); UL1 RR025741 (Northwestern University Clinical and
Translational Sciences Institute, Northwestern University); UL1 RR024153
(University of Pittsburgh Clinical and Translational Science Institute,
University of Pittsburgh); UL1 RR025758 (Harvard Catalyst: The Harvard
Clinical and Translational Science Center, Harvard University); UL1
RR024146 (UC Davis Clinical and Translational Science Center, University
of California, Davis); UL1 RR024986 (Michigan Institute for Clinical and
Health Research, University of Michigan at Ann Arbor); and UL1 RR024160
(University of Rochester Clinical and Translational Sciences Institute,
University of Rochester School of Medicine and Dentistry). Its contents
are solely the responsibility of the authors and do not necessarily
represent the official views of the NIH.
NR 13
TC 3
Z9 3
U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD MAY
PY 2012
VL 71
IS 5
BP 619
EP 624
DI 10.1038/pr.2012.5
PG 6
WC Pediatrics
SC Pediatrics
GA 933PC
UT WOS:000303373300014
PM 22398699
ER
PT J
AU Pickens, CL
Cifani, C
Navarre, BM
Eichenbaum, H
Theberge, FR
Baumann, MH
Calu, DJ
Shaham, Y
AF Pickens, Charles L.
Cifani, Carlo
Navarre, Brittany M.
Eichenbaum, Hila
Theberge, Florence R.
Baumann, Michael H.
Calu, Donna J.
Shaham, Yavin
TI Effect of fenfluramine on reinstatement of food seeking in female and
male rats: implications for the predictive validity of the reinstatement
model
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Animal models; Fenfluramine; Diet; Food self-administration; Predictive
validity; Reinstatement; Relapse; Stress
ID ANXIOGENIC DRUG YOHIMBINE; RECEPTOR PARTIAL AGONIST;
CORTICOTROPIN-RELEASING FACTOR; CUE-INDUCED REINSTATEMENT;
STRESS-INDUCED RELAPSE; COCAINE-SEEKING; ALCOHOL DEPENDENCE;
SMOKING-CESSATION; ETHANOL-SEEKING; EATING BEHAVIOR
AB Relapse to old unhealthy eating habits while dieting is often provoked by stress or acute exposure to palatable foods. We adapted a rat reinstatement model, which is used to study drug relapse, to study mechanisms of relapse to palatable food seeking induced by food-pellet priming (non-contingent exposure to a small amount of food pellets) or injections of yohimbine (an alpha-2 adrenoceptor antagonist that causes stress-like responses in humans and non-humans). Here, we assessed the predictive validity of the food reinstatement model by studying the effects of fenfluramine, a serotonin releaser with known anorectic effects, on reinstatement of food seeking.
We trained food-restricted female and male rats to lever-press for 45-mg food pellets (3-h sessions) and first assessed the effect of fenfluramine (0.75, 1.5, and 3.0 mg/kg, i.p.) on food-reinforced responding. Subsequently, we extinguished the food-reinforced responding and tested the effect of fenfluramine (1.5 and 3.0 mg/kg) on reinstatement of food seeking induced by yohimbine injections (2 mg/kg, i.p.) or pellet priming (four non-contingent pellets).
Fenfluramine decreased yohimbine- and pellet-priming-induced reinstatement. As expected, fenfluramine also decreased food-reinforced responding, but a control condition in which we assessed fenfluramine's effect on high-rate operant responding indicated that the drug's effect on reinstatement was not due to performance deficits.
The present data support the predictive validity of the food reinstatement model and suggest that this model could be used to identify medications for prevention of relapse induced by stress or acute exposure to palatable food during dietary treatments.
C1 [Pickens, Charles L.; Cifani, Carlo; Navarre, Brittany M.; Eichenbaum, Hila; Theberge, Florence R.; Baumann, Michael H.; Calu, Donna J.; Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Pickens, CL (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM pickensc@nida.nih.gov; yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014;
OI Cifani, Carlo/0000-0001-6180-828X; Calu, Donna/0000-0003-2377-9494
FU National Institute on Drug Abuse
FX The work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. CLP, CC, and BMN equally contributed
to this paper.
NR 107
TC 19
Z9 19
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2012
VL 221
IS 2
BP 341
EP 353
DI 10.1007/s00213-011-2585-9
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 934PT
UT WOS:000303457600014
PM 22134478
ER
PT J
AU Nadyrov, E
Rozhko, A
Kravtsov, V
Mabuchi, K
Hatch, M
Nakamura, N
Nikonovich, S
Aleksanin, S
AF Nadyrov, Eldar
Rozhko, Alexander
Kravtsov, Viacheslav
Mabuchi, Kiyohiko
Hatch, Maureen
Nakamura, Nori
Nikonovich, Sergey
Aleksanin, Sergey
TI Karyopathological traits of thyrocytes and exposure to radioiodines in
Belarusian children and adolescents following the accident at the
Chernobyl nuclear power plant
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Article
DE Thyroid gland; Thyrocytes; Nuclear abnormalities; Chernobyl fallout;
Belarus
ID THYROID-CANCER; CARCINOMA; UKRAINE; CELLS
AB The Belarus-American (BelAm) thyroid study cohort consists of persons who were 0-18 years of age at the time of exposure to radioactive iodine fallout from the 1986 Chernobyl nuclear power plant accident and who have undergone serial thyroid screenings with referral for fine-needle aspiration biopsy (FNAB) using standardized criteria. We investigated thyrocyte nuclear abnormalities in cytological samples from FNABs in 75 BelAm subjects with single and multiple thyroid nodules and 47 nodular goiter patients from Leningrad, Russia, unexposed to Chernobyl fallout. Nuclear abnormalities examined included internuclear chromosome bridges and derivative nuclei with broken bridges (i.e., "tailed" nuclei), which are formed from dicentric and ring chromosomes and thus may be cellular markers of radiation exposure. Among subjects with single-nodular goiter, thyrocytes with bridges were present in 86.8% of the exposed BelAm cohort compared with 27.0% of unexposed controls. The average frequency of thyrocytes with bridges and with tailed nuclei was also significantly higher in the BelAm subjects than in controls. Among subjects with multinodular goiters, thyrocytes with bridges were present in 75.7% of exposed BelAm patients compared with 16.7% of unexposed controls; thyrocytes with tailed nuclei were observed in all of the BelAm subjects but in only 40% of controls, and the mean frequencies of bridges and tailed nuclei were significantly higher in the exposed group. Unusually, long bridges were detected in 29% of BelAm patients with single-nodular goiters and 35% of those with multinodular goiters, while no such abnormalities were observed among patients from the Leningrad region. In the exposed subjects from BelAm, we also found positive correlations between their estimated dose of Iodine-131 from Chernobyl fallout and the frequency of tailed nuclei (p = 0.008) and bridges (p = 0.09). Further study is needed to confirm that these phenomena represent consequences of radiation exposure in the human organism.
C1 [Mabuchi, Kiyohiko; Hatch, Maureen] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Nadyrov, Eldar; Rozhko, Alexander; Nikonovich, Sergey] Republican Res Ctr Radiat Med & Human Ecol, Gomel, Byelarus.
[Kravtsov, Viacheslav; Aleksanin, Sergey] EMERCOM Russia, Nikiforov Russian Ctr Emergency & Radiat Med, St Petersburg, Russia.
[Nakamura, Nori] Radiat Effects Res Fdn, Hiroshima, Japan.
RP Hatch, M (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM hatchm@mail.nih.gov
FU U.S. National Cancer Institute, NIH, DHHS; Department of Energy; U.S.
Nuclear Regulatory Program; Ministry of Health of the Republic of
Belarus
FX This work was supported by the Intramural Research Program of the U.S.
National Cancer Institute, NIH, DHHS, and the Department of Energy, with
initial funds for equipment provided by the U.S. Nuclear Regulatory
Program. Support has also been provided by the Ministry of Health of the
Republic of Belarus within the limits of Government program performance.
NR 16
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAY
PY 2012
VL 51
IS 2
BP 187
EP 193
DI 10.1007/s00411-012-0407-z
PG 7
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 934RQ
UT WOS:000303464400008
PM 22382464
ER
PT J
AU Little, MP
AF Little, Mark P.
TI Heterogeneity of variation of relative risk by age at exposure in the
Japanese atomic bomb survivors (vol 48, pg 253, 2009)
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Correction
C1 NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
EM mark.little@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAY
PY 2012
VL 51
IS 2
BP 223
EP 223
DI 10.1007/s00411-012-0408-y
PG 1
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 934RQ
UT WOS:000303464400012
ER
PT J
AU Toy, BC
Koo, E
Cukras, C
Meyerle, CB
Chew, EY
Wong, WT
AF Toy, Brian C.
Koo, Euna
Cukras, Catherine
Meyerle, Catherine B.
Chew, Emily Y.
Wong, Wai T.
TI TREATMENT OF NONNEOVASCULAR IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2
WITH INTRAVITREAL RANIBIZUMAB Results of a Phase II Clinical Trial
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE anti-VEGF; clinical trial; idiopathic macular telangiectasia; IMT2;
ranibizumab
ID OPTICAL COHERENCE TOMOGRAPHY; SUBRETINAL NEOVASCULARIZATION SECONDARY;
JUXTAFOVEOLAR RETINAL TELANGIECTASIS; BEVACIZUMAB AVASTIN; FOLLOW-UP;
MEMBRANE; THERAPY; MICROPERIMETRY; PREVALENCE; VEGF
AB Purpose: To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2.
Methods: Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography.
Results: The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 +/- 7.5 letters) and control fellow eyes (+2.2 +/- 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 +/- 20% for study eyes, +1 +/- 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 +/- 7.0% for study eyes and -2.9 +/- 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes.
Conclusion: Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2. RETINA 32:996-1006, 2012
C1 [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Off Sci Director, NIH, 6 Ctr Dr,Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute; Clinical Research Training Program; National
Institutes of Health; Pfizer Inc
FX Supported by the National Eye Institute Intramural Research Program. B.
C. Toy and E. Koo were supported by the Clinical Research Training
Program, a public-private partnership supported jointly by the National
Institutes of Health and Pfizer Inc (via a grant to the Foundation for
National Institutes of Health from Pfizer).
NR 36
TC 12
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAY
PY 2012
VL 32
IS 5
BP 996
EP 1006
DI 10.1097/IAE.0b013e31824690a8
PG 11
WC Ophthalmology
SC Ophthalmology
GA 935EQ
UT WOS:000303502200018
PM 22266930
ER
PT J
AU Taveira-DaSilva, AM
Moss, J
AF Taveira-DaSilva, A. M.
Moss, J.
TI Progress in the treatment of lymphangioleiomyomatosis: From bench to
bedside
SO REVISTA PORTUGUESA DE PNEUMOLOGIA
LA English
DT Editorial Material
DE Lymphangioleiomyomatosis; Sirolimus therapy; mTOR
ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS;
LUNG-FUNCTION; SIROLIMUS; MUTATIONS; RAPAMYCIN; TSC2
C1 [Taveira-DaSilva, A. M.; Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002541-17]
NR 17
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER DOYMA SL
PI BARCELONA
PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN
SN 0873-2159
J9 REV PORT PNEUMOL
JI Rev. Port. Pneumol.
PD MAY-JUN
PY 2012
VL 18
IS 3
BP 142
EP 144
DI 10.1016/j.rppneu.2012.02.005
PG 3
WC Respiratory System
SC Respiratory System
GA 934MT
UT WOS:000303449100007
PM 22480994
ER
PT J
AU Maas, S
AF Maas, Stefan
TI Base modification RNA Editing: Information recoding on the fly
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Editorial Material
ID SITES
C1 [Maas, Stefan] Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA.
RP Maas, S (reprint author), NIGMS, NIH, 45 Ctr Dr,MSC 6200, Bethesda, MD 20892 USA.
EM Stefan.Maas@nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2012
VL 23
IS 3
BP 243
EP 243
DI 10.1016/j.semcdb.2011.12.002
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 935UT
UT WOS:000303547800001
PM 22193702
ER
PT J
AU Rider, CV
Dourson, ML
Hertzberg, RC
Mumtaz, MM
Price, PS
Simmons, JE
AF Rider, Cynthia V.
Dourson, Michael L.
Hertzberg, Richard C.
Mumtaz, Moiz M.
Price, Paul S.
Simmons, Jane Ellen
TI Incorporating Nonchemical Stressors Into Cumulative Risk Assessments
SO TOXICOLOGICAL SCIENCES
LA English
DT Editorial Material
DE joint action; exposure; dose response; modeling
ID HEALTH; PESTICIDE; FRAMEWORK; EXPOSURES; AGGREGATE
AB The role of nonchemical stressors in modulating the human health risk associated with chemical exposures is an area of increasing attention. On 9 March 2011, a workshop titled "Approaches for Incorporating Nonchemical Stressors into Cumulative Risk Assessment" took place during the 50th Anniversary Annual Society of Toxicology Meeting in Washington D.C. Objectives of the workshop included describing the current state of the science from various perspectives (i.e., regulatory, exposure, modeling, and risk assessment) and presenting expert opinions on currently available methods for incorporating nonchemical stressors into cumulative risk assessments. Herein, distinct frameworks for characterizing exposure to, joint effects of, and risk associated with chemical and nonchemical stressors are discussed.
C1 [Rider, Cynthia V.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Dourson, Michael L.] Toxicol Excellence Risk Assessment TERA, Cincinnati, OH 45211 USA.
[Hertzberg, Richard C.] Biomath Consulting, Atlanta, GA 30322 USA.
[Mumtaz, Moiz M.] Agcy Tox Subst & Dis Registry, Atlanta, GA 30333 USA.
[Price, Paul S.] Dow Chem Co USA, Midland, MI 48674 USA.
[Simmons, Jane Ellen] US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Rider, CV (reprint author), NIEHS, Natl Toxicol Program, 111 TW Alexander Dr,POB 12233,MD K2-12, Res Triangle Pk, NC 27709 USA.
EM ridercv@niehs.nih.gov
NR 20
TC 4
Z9 4
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAY
PY 2012
VL 127
IS 1
BP 10
EP 17
DI 10.1093/toxsci/kfs088
PG 8
WC Toxicology
SC Toxicology
GA 935AT
UT WOS:000303490100002
PM 22345310
ER
PT J
AU Ramsey, SD
Zeliadt, SB
Blough, DK
Fedorenko, CR
Fairweather, ME
McDermott, CL
Penson, DF
Van Den Eeden, SK
Hamilton, AS
Arora, NK
AF Ramsey, Scott D.
Zeliadt, Steven B.
Blough, David K.
Fedorenko, Catherine R.
Fairweather, Megan E.
McDermott, Cara L.
Penson, David F.
Van Den Eeden, Stephen K.
Hamilton, Ann S.
Arora, Neeraj K.
TI Complementary and Alternative Medicine Use, Patient-reported Outcomes,
and Treatment Satisfaction Among Men With Localized Prostate Cancer
SO UROLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; PREVALENCE; THERAPY; CAPSURE;
BOTHER
AB OBJECTIVE To evaluate the association between complementary and alternative medicine (CAM) use, satisfaction with treatment, and patient-reported outcomes after treatment.
METHODS The Prostate CAncer Therapy Selection Study prospectively surveyed patients newly diagnosed with localized prostate cancer about their treatment decision-making process and outcomes. The Prostate CAncer Therapy Selection Study recruited patients from 3 geographic areas through hospital-based urology clinics and community urology practices.
RESULTS More than 700 patients completed the baseline and follow-up surveys. More than 50% of respondents reported using CAM; this decreased to 39% if prayer was excluded as a type of CAM. On multivariate analysis, factors related to communication with the treating physician, but not CAM use, were associated with treatment satisfaction. The likelihood of stability or improvement in urinary, bowel, and sexual function at 6 months was related to the choice of primary therapy but was unrelated to CAM use.
CONCLUSION In the present prospective observational study, CAM use was highly prevalent but unrelated to treatment satisfaction or changes in functional status. The effect of CAM on these endpoints remains to be established in comparative effectiveness studies. UROLOGY 79: 1034-1041, 2012. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA.
Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA.
RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA.
EM sramsey@fhcrc.org
FU National Cancer Institute [HHSN261200900582P, N01-PC-35142,
N01-PC-35139, N01-PC-35136]; Cancer Surveillance System of the Fred
Hutchinson Cancer Research Center; Fred Hutchinson Cancer Research
Center; State of Washington
FX This publication was supported by the National Cancer Institute (grants
HHSN261200900582P, N01-PC-35142, N01-PC-35139, and N01-PC-35136) and by
the Cancer Surveillance System of the Fred Hutchinson Cancer Research
Center, funded by contract N01-PC-35142 from the Surveillance,
Epidemiology, and End Results (SEER) Program of the National Cancer
Institute, with additional support from the Fred Hutchinson Cancer
Research Center and the State of Washington.
NR 28
TC 4
Z9 4
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD MAY
PY 2012
VL 79
IS 5
BP 1034
EP 1041
DI 10.1016/j.urology.2012.01.023
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 934TW
UT WOS:000303470600022
PM 22546381
ER
PT J
AU Xun, P
Liu, K
Loria, CM
Bujnowski, D
Shikany, JM
Schreiner, PJ
Sidney, S
He, K
AF Xun, Pengcheng
Liu, Kiang
Loria, Catherine M.
Bujnowski, Deborah
Shikany, James M.
Schreiner, Pamela J.
Sidney, Stephen
He, Ka
TI Folate intake and incidence of hypertension among American young adults:
a 20-y follow-up study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; ARTERY RISK DEVELOPMENT; BLOOD-PRESSURE;
FOLIC-ACID; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; CONTROLLED TRIAL;
NATIONAL-HEALTH; CARDIA; HOMOCYSTEINE
AB Background: Laboratory studies suggest that folate intake may decrease blood pressure (BP) through increasing nitric oxide synthesis in endothelial cells and/or reducing plasma homocysteine concentrations. However, human studies, particularly longitudinal data, are limited.
Objective: Our objective was to investigate whether dietary folate intake is associated with the 20-y incidence of hypertension.
Design: We prospectively followed 4400 men and women (African Americans and whites aged 18-30 y) without hypertension at base-line (1985) in the Coronary Artery Risk Development in Young Adults study 6 times, in 1987, 1990, 1992, 1995, 2000, and 2005. Diet was assessed by dietary-history questionnaire at baseline and in 1992 and 2005. Incident hypertension was defined as the first occurrence at any follow-up examination of systolic BP >= 140 mm Hg, diastolic BP >= 90 mm Hg, or use of antihypertensive medication.
Results: A total of 989 incident cases were identified during the 20-y follow-up. After adjustment for potential confounders, participants in the highest quintile of total folate intake had a significantly lower incidence of hypertension (HR: 0.48; 95% CI: 0.38, 0.62; P-trend < 0.01) than did those in the lowest quintile. The multivariable HRs for the same comparison were 0.33 (95% Cl: 0.22, 0.51; P-trend < 0.01) in whites and 0.54 (95% CI: 0.40, 0.75; P-trend < 0.01) in African Americans (P-interaction = 0.047). The inverse associations were confirmed in a subset of the cohort (n = 1445) with serum folate measured at baseline and in 1992 and 2000.
Conclusions: Higher folate intake in young adulthood was longitudinally associated with a lower incidence of hypertension later in life. This inverse association was more pronounced in whites. Additional studies are warranted to establish the causal inference. Am J Clin Nutr 2012;95:1023-30.
C1 [Xun, Pengcheng; Bujnowski, Deborah; He, Ka] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Xun, Pengcheng; Bujnowski, Deborah; He, Ka] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA.
[Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Sidney, Stephen] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA.
RP He, K (reprint author), Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, 2221 McGavran Greenberg,Campus Box 7461, Chapel Hill, NC 27599 USA.
EM kahe@unc.edu
RI Xun, Pengcheng/D-3411-2013
FU National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-95095]; [R01HL081572]
FX Supported in part by grant R01HL081572 (PX and KH); CARDIA was supported
by grants N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and
N01-HC-95095 from the National Heart, Lung, and Blood Institute.
NR 35
TC 11
Z9 13
U1 1
U2 7
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAY
PY 2012
VL 95
IS 5
BP 1023
EP 1030
DI 10.3945/ajcn.111.027250
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 930LK
UT WOS:000303140700006
PM 22492371
ER
PT J
AU Bailey, RL
Holden, J
Dwyer, JT
AF Bailey, Regan L.
Holden, Joanne
Dwyer, Johanna T.
TI Intakes of copper in nutrition surveys are falsely high Reply
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Letter
C1 [Bailey, Regan L.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Holden, Joanne] ARS, Nutrient Data Lab, USDA, Beltsville, MD USA.
RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAY
PY 2012
VL 95
IS 5
BP 1294
EP 1294
DI 10.3945/ajcn.112.035451
PG 1
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 930LK
UT WOS:000303140700044
ER
PT J
AU Pietrzak, RH
Goldstein, RB
Southwick, SM
Grant, BF
AF Pietrzak, Robert H.
Goldstein, Rise B.
Southwick, Steven M.
Grant, Bridget F.
TI Psychiatric Comorbidity of Full and Partial Posttraumatic Stress
Disorder Among Older Adults in the United States: Results From Wave 2 of
the National Epidemiologic Survey on Alcohol and Related Conditions
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Comorbidity; older adults; posttraumatic stress disorder
ID WORLD-WAR-II; PERSONALITY-DISORDER; COMBAT VETERANS; RISK-FACTORS;
PREVALENCE; TRAUMA; COMMUNITY; PTSD; IV; DISABILITY
AB Objectives: To present findings on the prevalence, correlates, and psychiatric comorbidity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition posttraumatic stress disorder (PTSD) and partial PTSD in a nationally representative sample of US. older adults. Design, Setting, and Participants: Face-to-face interviews with 9,463 adults age 60 years and older in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Measurements: Sociodemographic correlates; worst stressful experiences; comorbid lifetime mood, anxiety, substance use, and personality disorders; psychosocial functioning; and suicide attempts. Results: Lifetime prevalences +/- standard errors of PTSD and partial PTSD were 4.5% +/- 0.25 and 5.5% +/- 0.27, respectively. Rates were higher in women (5.7% +/- 0.37 and 6.5% +/- 0.39) than in men (3.1% +/- 0.31 and 4.3% +/- 0.37). Older adults with PTSD most frequently identified unexpected death of someone close, serious illness or injury to someone close, and their own serious or life-threatening illness as their worst stressful events. Older adults exposed to trauma but without full or partial PTSD and respondents with partial PTSD most often identified unexpected death of someone close, serious illness or injury to someone close, and indirect experience of 9/11 as their worst events. PTSD was associated with elevated odds of lifetime mood, anxiety, drug use, and borderline and narcissistic personality disorders and decreased psychosocial functioning. Partial PTSD was associated with elevated odds of mood, anxiety, and narcissistic and schizotypal personality disorders and poorer psychosocial functioning relative to older adults exposed to trauma but without full or partial PTSD. Conclusions: PTSD among older adults in the United States is slightly more prevalent than previously reported and is associated with considerable psychiatric comorbidity and psychosocial dysfunction. Partial PTSD is associated with significant psychiatric comorbidity, particularly with mood and other anxiety disorders. (Am J Geriatr Psychiatry 2012; 20:380-390)
C1 [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Natl Ctr Posttraumat Stress Disorder, VA Connecticut Healthcare Syst, Dept Psychiat,Sch Med, West Haven, CT 06516 USA.
[Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA.
RP Pietrzak, RH (reprint author), Yale Univ, Natl Ctr Posttraumat Stress Disorder, VA Connecticut Healthcare Syst, Dept Psychiat,Sch Med, 950 Campbell Ave 151-E, West Haven, CT 06516 USA.
EM robert.pietrzak@yale.edu
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institutes of Health, NIAAA; National Center for Posttraumatic Stress
Disorder; National Institute of Mental Health Summer Research Institute
in Geriatric Mental Health; CogState, Inc.
FX The National Epidemiologic Survey on Alcohol and Related Conditions is
funded by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA), with supplemental support from the National Institute on Drug
Abuse. This research was supported in part by the Intramural Program of
the National Institutes of Health, NIAAA. Preparation of this report was
supported in part by the National Center for Posttraumatic Stress
Disorder, the National Institute of Mental Health Summer Research
Institute in Geriatric Mental Health, and a private donation.; Dr.
Pietrzak receives partial salary support from CogState, Inc., for work
that bears no relationship to the present study.
NR 40
TC 45
Z9 47
U1 3
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAY
PY 2012
VL 20
IS 5
BP 380
EP 390
DI 10.1097/JGP.0b013e31820d92e7
PG 11
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 932MT
UT WOS:000303295900002
PM 22522959
ER
PT J
AU Pineda-Alvarez, DE
Solomon, BD
Roessler, E
Balog, JZ
Hadley, DW
Zein, WM
Brooks, BP
Muenke, M
AF Pineda-Alvarez, Daniel E.
Solomon, Benjamin D.
Roessler, Erich
Balog, Joan Z.
Hadley, Donald W.
Zein, Wadih M.
Brooks, Brian P.
Muenke, Maximilian
TI Patients within the broad holoprosencephaly spectrum have distinct and
subtle ophthalmologic anomalies: Response to Khan
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Letter
ID SONIC-HEDGEHOG; CORNEAL DIAMETER; MUTATIONS; PHENOTYPE; NANOPHTHALMOS;
VALIDATION; EXPRESSION; FOREBRAIN; GENOTYPE; CHILDREN
C1 [Pineda-Alvarez, Daniel E.; Solomon, Benjamin D.; Roessler, Erich; Balog, Joan Z.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Hadley, Donald W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Zein, Wadih M.; Brooks, Brian P.] NEI, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), Natl Human Genome Res, Med Genet Branch, Inst Natl Inst Hlth, 35 Convent Dr,Bldg 35 Room 1B202, Bethesda, MD 20814 USA.
EM mamuenke@mail.nih.gov
FU Intramural NIH HHS [ZIA HG000209-10]
NR 17
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAY
PY 2012
VL 158A
IS 5
BP 1244
EP 1245
DI 10.1002/ajmg.a.35207
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 928RH
UT WOS:000303000200045
PM 22645505
ER
PT J
AU Romero, R
Garite, TJ
Kim, MH
Quilligan, EJ
Bump, RC
Carson, SA
Copeland, LJ
Grobman, WA
Iams, JD
Jenkins, TR
Kilpatrick, SJ
Macones, GA
Parry, S
Phipps, MG
AF Romero, Roberto
Garite, Thomas J.
Kim, Moon H.
Quilligan, E. J.
Bump, Richard C.
Carson, Sandra A.
Copeland, Larry J.
Grobman, William A.
Iams, Jay D.
Jenkins, Todd R.
Kilpatrick, Sarah J.
Macones, George A.
Parry, Samuel
Phipps, Maureen G.
TI The new American Journal of Obstetrics & Gynecology, 5 years later:
looking back and moving forward
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID PELVIC-INFLAMMATORY-DISEASE; ELEVATED LIVER-ENZYMES; HEART-RATE; SEVERE
PREECLAMPSIA; AMNIOTIC-FLUID; UNITED-STATES; FETAL WEIGHT; PREGNANCY;
WOMEN; MANAGEMENT
C1 [Romero, Roberto; Garite, Thomas J.; Kim, Moon H.; Quilligan, E. J.; Bump, Richard C.; Carson, Sandra A.; Copeland, Larry J.; Grobman, William A.; Iams, Jay D.; Jenkins, Todd R.; Kilpatrick, Sarah J.; Macones, George A.; Parry, Samuel; Phipps, Maureen G.] NICHD, Perinatol Res Branch, Program Perinatal Res & Obstet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Program Perinatal Res & Obstet, NIH,DHHS, Bethesda, MD 20892 USA.
NR 141
TC 4
Z9 4
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 2012
VL 206
IS 5
BP 364
EP 373
DI 10.1016/j.ajog.2012.03.008
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 931JB
UT WOS:000303211100008
PM 22542111
ER
PT J
AU Laughon, SK
Branch, DW
Beaver, J
Zhang, J
AF Laughon, S. Katherine
Branch, D. Ware
Beaver, Julie
Zhang, Jun
TI Changes in labor patterns over 50 years
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE labor; labor curve; labor duration
ID GRAPHICOSTATISTICAL ANALYSIS; NULLIPAROUS WOMEN; ARREST
AB OBJECTIVE: The objective of the study was to examine differences in labor patterns in a modern cohort compared with the 1960s in the United States.
STUDY DESIGN: Data from pregnancies at term, in spontaneous labor, with cephalic, singleton fetuses were compared between the Collaborative Perinatal Project (CPP, n = 39,491 delivering 1959-1966) and the Consortium on Safe Labor (CSL; n = 98,359 delivering 2002-2008).
RESULTS: Compared with the CPP, women in the CSL were older (26.8 +/- 6.0 vs 24.1 +/- 6.0 years), heavier (body mass index 29.9 +/- 5.0 vs 26.3 +/- 4.1 kg/m(2)), had higher epidural (55% vs 4%) and oxytocin use (31% vs 12%), and cesarean delivery (12% vs 3%). First stage of labor in the CSL was longer by a median of 2.6 hours in nulliparas and 2.0 hours in multiparas, even after adjusting for maternal and pregnancy characteristics, suggesting that the prolonged labor is mostly due to changes in practice patterns.
CONCLUSION: Labor is longer in the modern obstetrical cohort. The benefit of extensive interventions needs further evaluation.
C1 [Laughon, S. Katherine; Beaver, Julie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Branch, D. Ware] Intermt Healthcare, Salt Lake City, UT USA.
[Branch, D. Ware] Univ Utah, Salt Lake City, UT USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, MOE, Shanghai 200030, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Childrens Environm Hlth, Xinhua Hosp, Shanghai 200030, Peoples R China.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
OI Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX The data included in this paper were partly obtained from the Consortium
on Safe Labor, supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (contract number
HHSN267200603425C). The other institutions in the Consortium on Safe
Labor are listed with the Acknowledgments section.
NR 15
TC 0
Z9 4
U1 3
U2 7
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 MAY
PY 2012
VL 206
IS 5
AR 419.e1
DI 10.1016/j.ajog.2012.03.003
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 931JB
UT WOS:000303211100019
PM 22542117
ER
PT J
AU Haskell, WL
Troiano, RP
Hammond, JA
Phillips, MJ
Strader, LC
Marquez, DX
Grant, SF
Ramos, E
AF Haskell, William L.
Troiano, Richard P.
Hammond, Jane A.
Phillips, Michael J.
Strader, Lisa C.
Marquez, David X.
Grant, Struan F.
Ramos, Erin
TI Physical Activity and Physical Fitness Standardizing Assessment with the
PhenX Toolkit
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID CARDIORESPIRATORY FITNESS; ACTIVITY QUESTIONNAIRE; OLDER-ADULTS;
VALIDATION; EXERCISE; PERFORMANCE; PREDICTION; MORTALITY; GENOMICS;
BEHAVIOR
AB The focus of the PhenX (Phenotypes and eXposures) Toolkit is to provide researchers whose expertise lies outside a particular area with key measures identified by experts for uniform use in large-scale genetic studies and other extensive epidemiologic efforts going forward. The current paper specifically addresses the PhenX Toolkit research domain of physical activity and physical fitness (PA/PF), which are often associated with health outcomes. A Working Group (WG) of content experts completed a 6-month consensus process in which they identified a set of 14 high-priority, low-burden, and scientifically supported measures. During this process, the WG considered self-reported and objective measures that included the latest technology (e.g., accelerometers, pedometers, and heart-rate monitors). They also sought the input of measurement experts and other members of the research community during their deliberations. A majority of the measures include protocols for children (or adolescents), adults, and older adults or are applicable to all ages.
Measures from the PA/PF domain and 20 other domains are publicly available and found at the PhenX Toolkit website, www.phenxtoolkit.org. The use of common measures and protocols across large studies enhances the capacity to combine or compare data across studies, benefiting both PA/PF experts and non-experts. Use of these common measures by the research community should increase statistical power and enhance the ability to answer scientific questions that previously might have gone unanswered. (Am J Prev Med 2012;42(5):486-492) (C) 2012 American Journal of Preventive Medicine
C1 [Haskell, William L.] Stanford Univ, Sch Med, Prevent Res Ctr, Dept Med, Palo Alto, CA 94304 USA.
[Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Ramos, Erin] NHGRI, NIH, Rockville, MD USA.
[Hammond, Jane A.; Phillips, Michael J.; Strader, Lisa C.] RTI Int, Res Triangle Pk, NC USA.
[Marquez, David X.] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA.
[Grant, Struan F.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Haskell, WL (reprint author), Stanford Univ, Sch Med, Prevent Res Ctr, Dept Med, 1070 Arastradero Rd,Suite 100, Palo Alto, CA 94304 USA.
EM whaskell@stanford.edu
RI Strader, Lisa/H-3083-2013;
OI Troiano, Richard/0000-0002-6807-989X
FU NHGRI [U01 HG004597-01]
FX This work was supported by NHGRI, Award No. U01 HG004597-01.
NR 35
TC 3
Z9 3
U1 2
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2012
VL 42
IS 5
BP 486
EP 492
DI 10.1016/j.amepre.2011.11.017
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 928ED
UT WOS:000302963300014
PM 22516489
ER
PT J
AU Thota, AB
Sipe, TA
Byard, GJ
Zometa, CS
Hahn, RA
McKnight-Eily, LR
Chapman, DP
Abraido-Lanza, AF
Pearson, JL
Anderson, CW
Gelenberg, AJ
Hennessy, KD
Duffy, FF
Vernon-Smiley, ME
Nease, DE
Williams, SP
AF Thota, Anilkrishna B.
Sipe, Theresa Ann
Byard, Guthrie J.
Zometa, Carlos S.
Hahn, Robert A.
McKnight-Eily, Lela R.
Chapman, Daniel P.
Abraido-Lanza, Ana F.
Pearson, Jane L.
Anderson, Clinton W.
Gelenberg, Alan J.
Hennessy, Kevin D.
Duffy, Farifteh F.
Vernon-Smiley, Mary E.
Nease, Donald E., Jr.
Williams, Samantha P.
CA Community Preventive Serv Task
TI Collaborative Care to Improve the Management of Depressive Disorders A
Community Guide Systematic Review and Meta-Analysis
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; OLDER MEDICAL INPATIENTS; UK PRIMARY-CARE;
PREVENTIVE-SERVICES; UNITED-STATES; QUALITY IMPROVEMENT; CHRONIC
ILLNESS; HEALTH-CARE; TASK-FORCE; INTERVENTION
AB Context: To improve the quality of depression management, collaborative care models have been developed from the Chronic Care Model over the past 20 years. Collaborative care is a multicomponent, healthcare system-level intervention that uses case managers to link primary care providers, patients, and mental health specialists. In addition to case management support, primary care providers receive consultation and decision support from mental health specialists (i.e., psychiatrists and psychologists). This collaboration is designed to (1) improve routine screening and diagnosis of depressive disorders; (2) increase provider use of evidence-based protocols for the proactive management of diagnosed depressive disorders; and (3) improve clinical and community support for active client/patient engagement in treatment goal-setting and self-management.
Evidence acquisition: A team of subject matter experts in mental health, representing various agencies and institutions, conceptualized and conducted a systematic review and meta-analysis on collaborative care for improving the management of depressive disorders. This team worked under the guidance of the Community Preventive Services Task Force, a nonfederal, independent, volunteer body of public health and prevention experts. Community Guide systematic review methods were used to identify, evaluate, and analyze available evidence.
Evidence synthesis: An earlier systematic review with 37 RCTs of collaborative care studies published through 2004 found evidence of effectiveness of these models in improving depression outcomes. An additional 32 studies of collaborative care models conducted between 2004 and 2009 were found for this current review and analyzed. The results from the meta-analyses suggest robust evidence of effectiveness of collaborative care in improving depression symptoms (standardized mean difference [SMD] = 0.34); adherence to treatment (OR = 2.22); response to treatment (OR = 1.78); remission of symptoms (OR = 1.74); recovery from symptoms (OR = 1.75); quality of life/functional status (SMD = 0.12); and satisfaction with care (SMD = 0.39) for patients diagnosed with depression (all effect estimates were significant).
Conclusions: Collaborative care models are effective in achieving clinically meaningful improvements in depression outcomes and public health benefits in a wide range of populations, settings, and organizations. Collaborative care interventions provide a supportive network of professionals and peers for patients with depression, especially at the primary care level. (Am J Prev Med 2012;42(5):525-538) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Thota, Anilkrishna B.; Sipe, Theresa Ann; Byard, Guthrie J.; Zometa, Carlos S.; Hahn, Robert A.] CDC, Community Guide Branch, Epidemiol & Anal Program Off, Off Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA.
[McKnight-Eily, Lela R.; Chapman, Daniel P.] CDC, Div Populat Hlth, Atlanta, GA 30333 USA.
[Vernon-Smiley, Mary E.] CDC, Div Adolescent & Sch Hlth, Atlanta, GA 30333 USA.
[Williams, Samantha P.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Williams, Samantha P.] CDC, Behav Intervent & Res Branch, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30333 USA.
[Abraido-Lanza, Ana F.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Pearson, Jane L.] NIMH, Bethesda, MD 20892 USA.
[Hennessy, Kevin D.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Anderson, Clinton W.] Amer Psychol Assoc, Washington, DC 20036 USA.
[Gelenberg, Alan J.] Penn State Hershey Med Ctr, Dept Psychiat, Hershey, PA USA.
[Duffy, Farifteh F.] Amer Psychiat Assoc, Arlington, VA USA.
[Nease, Donald E., Jr.] Amer Acad Family Phys, Denver, CO USA.
RP Thota, AB (reprint author), CDC, Community Guide Branch, Epidemiol & Anal Program Off, Off Surveillance Epidemiol & Lab Serv, 1600 Clifton Rd,Mailstop E69, Atlanta, GA 30333 USA.
EM athota@cdc.gov
RI Thota, Anilkrishna/J-1743-2012; Nease, Donald/B-6206-2013
OI Nease, Donald/0000-0001-8323-3720
FU Pfizer Pharmaceuticals
FX AJG is a major stock owner of Healthcare Technology Stystems, Inc.; he
consults to Dey Pharma, PGxHealth, Myriad Genetics, and Zynx Health; and
is the principal investigator on an investigator-initiated grant from
Pfizer Pharmaceuticals to Penn State. No other financial disclosures
were reported by the authors of this paper.
NR 76
TC 148
Z9 149
U1 8
U2 41
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2012
VL 42
IS 5
BP 525
EP 538
DI 10.1016/j.amepre.2012.01.019
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 928ED
UT WOS:000302963300020
PM 22516495
ER
PT J
AU Balshaw, DM
Kwok, RK
AF Balshaw, David M.
Kwok, Richard K.
TI Innovative Methods for Improving Measures of the Personal Environment
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 [Balshaw, David M.] NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA.
[Kwok, Richard K.] NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
RP Balshaw, DM (reprint author), NIEHS, Div Extramural Res & Training, MD K3-04,POB 12233, Res Triangle Pk, NC 27709 USA.
EM balshaw@niehs.nih.gov
RI Kwok, Richard/B-6907-2017
OI Kwok, Richard/0000-0002-6794-8360
NR 10
TC 3
Z9 3
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2012
VL 42
IS 5
BP 558
EP 559
DI 10.1016/j.amepre.2012.02.002
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 928ED
UT WOS:000302963300025
PM 22516500
ER
PT J
AU Epperson, CN
Steiner, M
Hartlage, SA
Eriksson, E
Schmidt, PJ
Jones, I
Yonkers, KA
AF Epperson, C. Neill
Steiner, Meir
Hartlage, S. Ann
Eriksson, Elias
Schmidt, Peter J.
Jones, Ian
Yonkers, Kimberly A.
TI Premenstrual Dysphoric Disorder: Evidence for a New Category for DSM-5
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Review
ID LATE LUTEAL-PHASE; POSTTRAUMATIC-STRESS-DISORDER; PLACEBO-CONTROLLED
TRIAL; COMMUNITY-BASED SAMPLE; POPULATION-BASED TWIN; LONG-TERM
TREATMENT; MENSTRUAL-CYCLE; SYMPTOM SEVERITY; MOOD DISORDER;
ENVIRONMENTAL-FACTORS
AB Premenstrual dysphoric disorder, which affects 2%-5% of premenopausal women, was included in Appendix B of DSMIV, "Criterion Sets and Axes Provided for Further Study." Since then, aided by the inclusion of specific and rigorous criteria in DSM-IV, there has been an explosion of research on the epidemiology, phenomenology, pathogenesis, and treatment of the disorder. In 2009, the Mood Disorders Work Group for DSM-5 convened a group of experts to examine the literature on premenstrual dysphoric disorder and provide recommendations regarding the appropriate criteria and placement for the disorder in DSM-5. Based on thorough review and lengthy discussion, the work group proposed that the information on the diagnosis, treatment, and validation of the disorder has matured sufficiently for it to qualify as a full category in DSM-5. A move to the position of category, rather than a criterion set in need of further study, will provide greater legitimacy for the disorder and encourage the growth of evidence-based research, ultimately leading to new treatments.
C1 [Epperson, C. Neill] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
Univ Penn, Perelman Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
McMaster Univ, Dept Psychiat, Hamilton, ON, Canada.
Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA.
Univ Gothenburg, Sahlgrenska Acad, Dept Pharmacol, Gothenburg, Sweden.
Univ Gothenburg, Sahlgrenska Acad, Inst Physiol & Neurosci, Gothenburg, Sweden.
NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales.
Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
RP Epperson, CN (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
EM cepp@upenn.edu
OI Steiner, Meir/0000-0001-7838-2246
FU Shire; Canadian Institutes of Health Research; APA; GlaxoSmithKline; Eli
Lilly; NIMH; National Institute on Drug Abuse
FX Dr. Epperson has received research support from Shire for an
investigator-initiated study, has received donation of products for
research purposes from Novartis, and holds equity in Johnson & Johnson
and Merck. Dr. Steiner has served as a consultant for AstraZeneca,
Azevan, Bayer Canada, and Servier, has received research grants from the
Canadian Institutes of Health Research, and has received honoraria from
AstraZeneca and the Society for Women's Health Research. Dr. Hartlage
received funding from APA to conduct secondary analyses of data sets on
premenstrual dysphoric disorder. Dr. Eriksson has served on advisory
boards for Lundbeck and Schering-Bayer and has received consultancy fees
and research grants from Lundbeck. Dr. Schmidt reports no financial
relationships with commercial interests. Dr. Jones has received
honoraria or consultancy fees from AstraZeneca, Eli Lilly,
GlaxoSmithKline, Janssen-Cilag, Lundbeck, and Sanofi-Aventis and has
received research funding from GlaxoSmithKline. Dr. Yonkers has received
research support from Eli Lilly, NIMH, and the National Institute on
Drug Abuse, study medication from Pfizer for an NIMH-funded trial, and
royalties from UpToDate; she also received funding from APA to conduct
secondary analyses of data sets on premenstrual dysphoric disorder.
NR 103
TC 63
Z9 66
U1 4
U2 16
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD MAY
PY 2012
VL 169
IS 5
BP 465
EP 475
DI 10.1176/appi.ajp.2012.11081302
PG 11
WC Psychiatry
SC Psychiatry
GA 932LJ
UT WOS:000303292300009
PM 22764360
ER
PT J
AU Robbins, IM
Moore, TM
Blaisdell, CJ
Abman, SH
AF Robbins, Ivan M.
Moore, Timothy M.
Blaisdell, Carol J.
Abman, Steven H.
TI Improving Outcomes for Pulmonary Vascular Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE clinical trials; pediatrics; pulmonary hypertension; pulmonary vascular
changes
ID ARTERIAL-HYPERTENSION; SURVIVAL; CHILDREN; FRANCE
AB Recognizing the importance of improving lung health through lung disease research, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of multidisciplinary experts for the following purpose: (1) to review the current scientific knowledge underlying the basis for treatment of adults and children with pulmonary vascular diseases (PVDs); (2) to identify gaps, barriers, and emerging scientific opportunities in translational PVD research and the means to capitalize on these opportunities; (3) to prioritize new research directions that would he expected to affect the clinical course of PVDs; and (4) to make recommendations to the NHLBI on how to fill identified gaps in adult and pediatric PVD clinical research. Workshop participants reviewed experiences from previous PVD clinical trials and ongoing clinical research networks with other lung disorders, including acute respiratory distress syndrome, chronic obstructive lung disease, and idiopathic pulmonary fibrosis, as well. Bioinformatics experts discussed strategies for applying cutting-edge health information technology to clinical studies. Participants in the workshop considered approaches in the following broad concept areas: (1) improved phenotyping to identify potential subjects for appropriate PVD clinical studies; (2) identification of potential new end points for assessing key outcomes and developing better-designed PVD clinical trial.; and (3) the establishment of priorities for specific clinical research needed to advance care of patients with various subsets of PVDs from childhood through adulthood. This report provides a summary of the objectives and recommendations to the NHLBI concentrating on clinical research efforts that are needed to better diagnose and treat PVDs.
C1 [Moore, Timothy M.] NHLBI, Div Lung Dis, Nihon Univ, Rockledge Ctr 2, Bethesda, MD 20892 USA.
[Robbins, Ivan M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Abman, Steven H.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA.
[Abman, Steven H.] Childrens Hosp, Denver, CO 80218 USA.
RP Moore, TM (reprint author), NHLBI, Div Lung Dis, Nihon Univ, Rockledge Ctr 2, Suite 10042,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM tim.moore@nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX This Workshop was supported by the National Heart, Lung, and Blood
Institute, National Institutes of Health.
NR 11
TC 9
Z9 9
U1 0
U2 3
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 MAY 1
PY 2012
VL 185
IS 9
BP 1015
EP 1020
DI 10.1164/rccm.201201-0049WS
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 930ZE
UT WOS:000303182700017
PM 22335936
ER
PT J
AU Yao, L
Gai, N
AF Yao, Lawrence
Gai, Neville
TI Fat-Corrected T2 Measurement as a Marker of Active Muscle Disease in
Inflammatory Myopathy
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE MRI; muscle; myopathy; myositis; T2
ID JUVENILE DERMATOMYOSITIS; ARTICULAR-CARTILAGE; MATHEMATICAL-THEORY;
RELAXATION-TIMES; SPIN-ECHO; WATER; QUANTIFICATION; IDEAL; T-2;
QUANTITATION
AB OBJECTIVE. We sought to improve the utility of T2 measurement as a marker of active muscle disease in patients with idiopathic inflammatory myopathy by correcting for T2 prolongations caused by fatty replacement of muscle that accompnaies chronic muscle damage.
SUBJECTS AND METHODS. Twenty-one patients with idiopathic inflammatory myopathy underwent a standardized MRI evaluation of the thighs. Fat fraction maps were calculated from dual-echo gradient-echo images. Fat-corrected T2 maps were generated from multiecho spin-echo images on the basis of a biexponential model that incorporated voxelwise fat fraction estimates. Semiautomated summaries of conventional and fat-corrected muscle T2 values were compared with one another and with standardized visual scores of muscle disease based on T1-weighted spin-echo and STIR images.
RESULTS. Fat-corrected muscle T2 maps showed lower mean values and greater histogram entropy than conventional T2 maps, as analyzed over a standardized portion of the thigh muscles. Conventional and fat-corrected T2 values correlated with visual scores of active muscle disease on STIR images and with the varying intensity of disease depicted with STIR in focal muscle regions.
CONCLUSION. MRI T2 maps of muscle can be corrected for varying fat content by combining the information from chemical shift-sensitive gradient-echo and multiecho spinecho images. Use of this strategy may prove useful in the study of idiopathic inflammatory myopathy and other diseases characterized by both muscle inflammation and atrophy.
C1 [Yao, Lawrence; Gai, Neville] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Yao, L (reprint author), NIH, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM lyao@cc.nih.gov
FU Clinical Center, National Institutes of Health
FX Supported in part by the Intramural Research Program at the Clinical
Center, National Institutes of Health.
NR 24
TC 14
Z9 14
U1 2
U2 6
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 MAY
PY 2012
VL 198
IS 5
BP W475
EP W481
DI 10.2214/AJR.11.7113
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 930TG
UT WOS:000303162800010
PM 22528929
ER
PT J
AU Sheehan, FT
Sipprell, WH
Boden, BP
AF Sheehan, Frances T.
Sipprell, William H., III
Boden, Barry P.
TI Dynamic Sagittal Plane Trunk Control During Anterior Cruciate Ligament
Injury
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE ACL injury; injury prevention; gender differences
ID QUADRICEPS FEMORIS MUSCLE; NEUROMUSCULAR CONTROL; COMPUTER-SIMULATION;
VIDEO ANALYSIS; KNEE INJURY; FOLLOW-UP; RISK; JOINT; MECHANISMS;
KINEMATICS
AB Background: Recent studies have demonstrated that trunk control likely plays a role in anterior cruciate ligament (ACL) injury. Yet, the majority of ACL research remains focused on the lower limb, with limited information on the trunk position at the time of injury.
Hypotheses: Athletes experiencing a noncontact ACL injury after a 1-legged landing position their center of mass (COM) more posterior from the base of support (BOS) at initial ground contact in comparison with uninjured athletes. The distance from the COM to the BOS (COM_BOS) is larger in female, as compared with male, athletes during 1-legged landing.
Study Design: Case control study; Level of evidence, 3.
Methods: Movie captures of 20 athletes performing a 1-legged landing maneuver resulting in a torn ACL were compared with matched (for gender, sport, and activity just before landing) movie captures of 20 athletes performing a similar maneuver that did not result in an ACL disruption (controls). The COM_BOS, trunk(G) angle, and limbG angle (both relative to the gravity vector) were measured in the sagittal plane at initial ground-foot contact. A 2-way ANOVA (injury status x gender) was used to examine the hypotheses.
Results: There was a significant difference in all 3 measures based on injury status but not on gender. The COM_BOS, normalized by femur length, and limbG angle were greater (Delta = 0.9, P < .001 and Delta = 16 degrees, P = .004, respectively), and the trunkG angle was smaller (Delta = 12 degrees, P = .016) in the participants who sustained an ACL injury as compared with controls. The average COM was calculated as 38 cm more posterior relative to the BOS in the participants who sustained an ACL injury as compared with controls.
Conclusion: Landing with the COM far posterior to the BOS may be a risk factor for noncontact ACL injury and potentially can be addressed in prevention programs.
C1 [Sheehan, Frances T.; Sipprell, William H., III; Boden, Barry P.] NIH, Funct & Appl Biomech Sect Rehabil Med, Bethesda, MD 20892 USA.
RP Boden, BP (reprint author), Orthopaed Ctr, 9420 Key W Ave,Suite 300, Rockville, MD 20850 USA.
EM bboden@starpower.net
RI sheehan, frances/B-6962-2009
FU National Institutes of Health (NIH); Clinical Center at the NIH
FX One or more of the authors has declared the following potential conflict
of interest or source of funding: This research was supported by the
Intramural Research Program of the National Institutes of Health (NIH)
and the Clinical Center at the NIH.
NR 32
TC 23
Z9 23
U1 1
U2 23
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD MAY
PY 2012
VL 40
IS 5
BP 1068
EP 1074
DI 10.1177/0363546512437850
PG 7
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 932XN
UT WOS:000303323900016
PM 22383659
ER
PT J
AU Danziger-Isakov, L
Mohanakumar, T
Heeger, P
Steward, N
Worley, S
Conrad, C
Faro, A
Goldfarb, S
Hayes, D
Schecter, M
Spencer, H
Visner, G
Williams, N
Ikle, D
Sweet, SC
AF Danziger-Isakov, L.
Mohanakumar, T.
Heeger, P.
Steward, N.
Worley, S.
Conrad, C.
Faro, A.
Goldfarb, S.
Hayes, D., Jr.
Schecter, M.
Spencer, H.
Visner, G.
Williams, N.
Ikle, D.
Sweet, S. C.
TI Antibodies to Self Antigens (Collagen V & K-alpha 1tubulin) in Pediatric
Lung Transplant
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Danziger-Isakov, L.; Worley, S.] Cleveland Clin, Cleveland, OH USA.
[Mohanakumar, T.; Steward, N.; Faro, A.; Sweet, S. C.] Washington Univ, St Louis, MO 63130 USA.
[Heeger, P.] Mt Sinai Med Ctr, New York, NY USA.
[Conrad, C.] Stanford Univ, Stanford, CA 94305 USA.
[Goldfarb, S.] Childrens Philadelphia, Philadelphia, PA USA.
[Visner, G.] Boston Childrens, Boston, MA USA.
[Williams, N.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 71
BP 48
EP 48
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235500072
ER
PT J
AU Chakkera, HA
Ayub, A
Gonwa, T
Knowler, WC
AF Chakkera, H. A.
Ayub, A.
Gonwa, T.
Knowler, W. C.
TI Validation of a Pretransplant Risk Score for New Onset Diabetes Mellitus
after Kidney Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Ayub, A.; Gonwa, T.] Mayo Clin, Jacksonville, FL USA.
[Knowler, W. C.] NIDDK, NIH, Phoenix, AZ USA.
NR 0
TC 1
Z9 1
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 MAY
PY 2012
VL 12
SU 3
SI SI
MA 153
BP 71
EP 71
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235500154
ER
PT J
AU Terrault, NA
Stravitz, RT
Lok, AS
Everson, GT
Brown, RS
Kulik, LB
Olthoff, KM
Saab, S
Rubinas, T
Argo, CK
Everhart, JE
Rodrigo, DR
AF Terrault, N. A.
Stravitz, R. T.
Lok, A. S.
Everson, G. T.
Brown, R. S., Jr.
Kulik, L. B.
Olthoff, K. M.
Saab, S.
Rubinas, T.
Argo, C. K.
Everhart, J. E.
Rodrigo, D. R.
TI Long-Term Hepatitis C (HCV) Graft Loss and Fibrosis Severity Is
Unrelated to Donor Type: Results from the Adult to Adult Living Donor
Liver Transplantation (A2ALL) Study
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Terrault, N. A.] UCSF, San Francisco, CA USA.
[Lok, A. S.; Rodrigo, D. R.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Everson, G. T.] Univ Colorado, Boulder, CO 80309 USA.
[Brown, R. S., Jr.] Columbia Univ, New York, NY 10027 USA.
[Olthoff, K. M.] Univ Penn, Philadelphia, PA 19104 USA.
[Saab, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Everhart, J. E.] NIDDK, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 270
BP 107
EP 107
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235500271
ER
PT J
AU Hall, E
Pfeiffer, R
Engels, E
Segev, D
AF Hall, E.
Pfeiffer, R.
Engels, E.
Segev, D.
TI Association of Induction Therapy with Cancer after Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Hall, E.; Segev, D.] Johns Hopkins, Baltimore, MD USA.
[Pfeiffer, R.; Engels, E.] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 528
BP 186
EP 186
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235501152
ER
PT J
AU Hall, E
Pfeiffer, R
Segev, D
Engels, E
AF Hall, E.
Pfeiffer, R.
Segev, D.
Engels, E.
TI Cumulative Incidence of Cancer after Solid Organ Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Hall, E.; Pfeiffer, R.; Engels, E.] NCI, Rockville, MD USA.
[Hall, E.; Segev, D.] Johns Hopkins, Baltimore, MD USA.
NR 0
TC 0
Z9 0
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 MAY
PY 2012
VL 12
SU 3
SI SI
MA 532
BP 187
EP 188
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235501156
ER
PT J
AU Burckart, GJ
Figg, WD
Brooks, MM
Green, D
Girnita, DM
Troutman, S
Chinnock, R
Canter, C
Addonizio, L
Bernstein, D
Kirklin, JK
Naftel, D
Price, DK
Zeevi, A
Webber, SA
AF Burckart, G. J.
Figg, W. D., II
Brooks, M. M.
Green, D.
Girnita, D. M.
Troutman, S.
Chinnock, R.
Canter, C.
Addonizio, L.
Bernstein, D.
Kirklin, J. K.
Naftel, D.
Price, D. K.
Zeevi, A.
Webber, S. A.
TI A Multi-Institutional Study of Outcomes after Pediatric Heart
Transplantation: Effect of ABCC2 Polymorphisms
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Burckart, G. J.; Green, D.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
[Figg, W. D., II; Troutman, S.; Price, D. K.] NCI, NIH, Bethesda, MD 20892 USA.
[Brooks, M. M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Girnita, D. M.; Zeevi, A.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA.
[Chinnock, R.] Washington Univ, Sch Med, Dept Pediat Cardiol, St Louis, MO USA.
[Canter, C.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Addonizio, L.] Stanford Univ, Div Pediat Cardiol, Palo Alto, CA 94304 USA.
[Bernstein, D.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Kirklin, J. K.; Naftel, D.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
NR 0
TC 0
Z9 0
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 MAY
PY 2012
VL 12
SU 3
SI SI
MA 820
BP 270
EP 270
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235502041
ER
PT J
AU Danziger-Isakov, L
Storch, G
Buller, R
Mason, S
Worley, S
Conrad, C
Faro, A
Goldfarb, S
Hayes, D
Schecter, M
Spencer, H
Visner, G
Williams, N
Ikle, D
Sweet, SC
AF Danziger-Isakov, L.
Storch, G.
Buller, R.
Mason, S.
Worley, S.
Conrad, C.
Faro, A.
Goldfarb, S.
Hayes, D., Jr.
Schecter, M.
Spencer, H.
Visner, G.
Williams, N.
Ikle, D.
Sweet, S. C.
TI Prospective Viral Recovery and Concordance between Nasopharyngeal &
Bronchoalveolar Lavage Specimens in Pediatric Lung Transplant
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Danziger-Isakov, L.; Worley, S.] Cleveland Clin, Cleveland, OH USA.
[Storch, G.; Buller, R.; Mason, S.; Faro, A.; Sweet, S. C.] Washington Univ, St Louis, MO 63130 USA.
[Conrad, C.] Lucile Packard Childrens, Palo Alto, CA USA.
[Goldfarb, S.] Childrens Philadelphia, Philadelphia, PA USA.
[Hayes, D., Jr.] Nationwide Childrens, Columbus, OH USA.
[Schecter, M.] Texas Childrens, Houston, TX USA.
[Visner, G.] Childrens Boston, Boston, MA USA.
[Williams, N.] NIH, Bethesda, MD USA.
[Ikle, D.] RHO Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 964
BP 309
EP 309
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235502185
ER
PT J
AU Ota, Y
Hisada, M
Cameron, AM
Zhang, X
Gao, B
Montgomery, RA
Williams, GM
Sun, Z
AF Ota, Y.
Hisada, M.
Cameron, A. M.
Zhang, X.
Gao, B.
Montgomery, R. A.
Williams, G. M.
Sun, Z.
TI Successful Transplantation of Reduced Sized Rat Alcoholic Fatty Livers
Made Possible by Mobilization of Host Stem Cells
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Ota, Y.; Hisada, M.; Cameron, A. M.; Zhang, X.; Montgomery, R. A.; Williams, G. M.; Sun, Z.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 1264
BP 399
EP 399
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235503167
ER
PT J
AU Singh, AA
Seavey, CN
Corcoran, PC
Hoyt, RF
Lewis, BGT
Thomas, ML
Ayares, D
Horvath, KA
Mohiuddin, MM
AF Singh, A. A.
Seavey, C. N.
Corcoran, P. C.
Hoyt, R. F.
Lewis, B. G. T.
Thomas, M. L.
Ayares, D.
Horvath, K. A.
Mohiuddin, M. M.
TI Increased Number of CD4+CD25 HIFOXP3+T Regulatory Cells in Recipient
Baboons Is Associated with Long-Term Pig Cardiac Xenograft Survival.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Singh, A. A.; Seavey, C. N.; Corcoran, P. C.; Horvath, K. A.; Mohiuddin, M. M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Hoyt, R. F.] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Lewis, B. G. T.; Thomas, M. L.] NIH, DVR, ORS, Bethesda, MD 20892 USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 1434
BP 448
EP 448
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235504009
ER
PT J
AU Mohiuddin, MM
Singh, AK
Corcoran, PC
Thomas, ML
Lewis, B
Hoyt, RF
Ayares, D
Reimann, KA
Horvath, KA
AF Mohiuddin, M. M.
Singh, A. K.
Corcoran, P. C.
Thomas, M. L.
Lewis, B.
Hoyt, R. F.
Ayares, D.
Reimann, K. A.
Horvath, K. A.
TI Co-Stimulation Blockade by Anti CD40 (Clone 2C10) Extends Graft Survival
Significantly and Has Multiple Advantages over Anti CD154 (5C8) and Anti
CD40 (3A8) Use in a Heterotopic Cardiac Xenotransplantation Model
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Mohiuddin, M. M.; Singh, A. K.; Corcoran, P. C.; Horvath, K. A.] NHLBI, NIH, Cardiothorac Surg Res Program, Bethesda, MD 20892 USA.
[Thomas, M. L.; Lewis, B.] NIH, ORS, DVR, Bethesda, MD 20892 USA.
[Hoyt, R. F.] NHLBI, NIH, LAMS, Bethesda, MD 20892 USA.
[Reimann, K. A.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 1719
BP 530
EP 531
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235504309
ER
PT J
AU Engels, EA
Preiksaitis, J
Zingone, A
Landgren, O
AF Engels, E. A.
Preiksaitis, J.
Zingone, A.
Landgren, O.
TI Circulating Antibody Free Light Chains and Risk of Posttransplant
Lymphoproliferative Disorder
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Epstein-Barr virus; immunology; lymphocyte activation; monoclonal
gammopathy of undertermined significance; posttransplant
lymphoproliferative disorder; tumor markers
ID EPSTEIN-BARR-VIRUS; ORGAN TRANSPLANT RECIPIENTS; MONOCLONAL GAMMOPATHY;
RHEUMATOID-ARTHRITIS; SERUM; EBV; LYMPHOMA; DISEASE; IMMUNOGLOBULINS;
INFLAMMATION
AB Posttransplant lymphoproliferative disorder (PTLD) is a major complication of solid-organ transplantation. With human immunodeficiency virus infection (an analogous immunosuppressive state), elevated kappa and lambda immunoglobulin free light chains (FLCs) in peripheral blood are associated with increased risk of lymphoma. To assess the role of B-cell dysfunction in PTLD, we measured circulating FLCs among Canadian transplant recipients, including 29 individuals with PTLD and 57 matched transplant recipients who were PTLD-free. Compared with controls, PTLD cases had higher kappa FLCs (median 1.53 vs. 1.07 times upper limit of normal) and lambda FLCs (1.03 vs. 0.68). Using samples obtained on average 3.5 months before PTLD diagnosis, cases were more likely to have polyclonal FLC elevations (i.e. elevated kappa and/or lambda with normal kappa/lambda ratio: odds ratio [OR] 4.2, 95%CI 1.115) or monoclonal elevations (elevated kappa and/or lambda with abnormal ratio: OR 3.0, 95%CI 0.518). Strong FLC-PTLD associations were also observed at diagnosis/selection. Among recipients with EpsteinBarr virus (EBV) DNA measured in blood, EBV DNAemia was associated with FLC abnormalities (ORs 6.2 and 3.2 for monoclonal and polyclonal elevations). FLC elevations are common in transplant recipients and associated with heightened PTLD risk. FLCs likely reflect B-cell dysfunction, perhaps related to EBV-driven lymphoproliferation.
C1 [Engels, E. A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Preiksaitis, J.] Univ Alberta, Dept Med, Div Infect Dis, Edmonton, AB, Canada.
[Zingone, A.; Landgren, O.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM engelse@exchange.nih.gov
FU National Cancer Institute
FX This study was funded by the intramural program of the National Cancer
Institute.
NR 32
TC 10
Z9 10
U1 1
U2 3
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 MAY
PY 2012
VL 12
IS 5
BP 1268
EP 1274
DI 10.1111/j.1600-6143.2011.03954.x
PG 7
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QT
UT WOS:000303235100025
PM 22300426
ER
PT J
AU Koulmanda, M
Qipo, A
Fan, Z
Smith, N
Auchincloss, H
Zheng, XX
Strom, TB
AF Koulmanda, M.
Qipo, A.
Fan, Z.
Smith, N.
Auchincloss, H.
Zheng, X. X.
Strom, T. B.
TI Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After
Short-Term Triple Therapy
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Islet allograft; nonhuman primate; transplantation; triple therapy
ID REGULATORY T-CELLS; ALLOGRAFT; TRANSPLANTATION; STREPTOZOTOCIN;
LYMPHOCYTES; TOLERANCE; PHENOTYPE; RESISTANT; REJECTION; BLOCKADE
AB Preclinical studies in nonhuman primates (NHP) are particularly useful to evaluate the safety and efficacy of new therapeutic proteins developed for use in clinical transplantation. We hypothesized that a treatment that selectively destroys activated cytopathic donor reactive T cells while sparing resting and immunoregulatory T cells in a mouse model might also produce long-term drug-free engraftment and tolerance without the hazards of lymphopenia in the challenging nonhuman primate islet allograft model. Short-term treatment with a regimen consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig cytolytic fusion proteins (triple therapy) posttransplantation results in prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow progressive loss of islet function in some recipients was not associated with obvious pathologic evidence of rejection.
C1 [Koulmanda, M.; Qipo, A.; Fan, Z.; Zheng, X. X.; Strom, T. B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Koulmanda, M.; Qipo, A.; Fan, Z.; Zheng, X. X.; Strom, T. B.] Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Dept Med, Transplant Inst, Boston, MA 02114 USA.
[Smith, N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Auchincloss, H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Auchincloss, H.] NIAID, Bethesda, MD 20892 USA.
[Zheng, X. X.] Univ Pittsburgh, Thomas Starzl Transplant Inst, Pittsburgh, PA USA.
RP Koulmanda, M (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
EM mkoulman@bidmc.harvard.edu
FU NIH [PO1 DK53087]; Juvenile Diabetes Research Foundation Center for
Islet Transplantation at Harvard Medical School
FX We thank Vaja Tchipashivili from the Joslin Diabetes Center for
providing monkey islets and Luba Zachachin for expert assistance with
tissue processing. This work was funded in part by the NIH PO1 DK53087
and the Juvenile Diabetes Research Foundation Center for Islet
Transplantation at Harvard Medical School.
NR 21
TC 10
Z9 10
U1 0
U2 2
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 MAY
PY 2012
VL 12
IS 5
BP 1296
EP 1302
DI 10.1111/j.1600-6143.2012.03973.x
PG 7
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QT
UT WOS:000303235100028
PM 22390179
ER
PT J
AU Sharma, V
Wikstrom, M
Kaila, VRI
AF Sharma, Vivek
Wikstrom, Marten
Kaila, Ville R. I.
TI Dynamic water networks in cytochrome cbb(3) oxidase
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article
DE Proton channel; Proton pumping; cbb(3)-type cytochrome c oxidase;
Continuum electrostatics; Density functional theory (DFT); Molecular
dynamics (MD) simulation
ID COPPER OXYGEN REDUCTASES; SITE-DIRECTED MUTAGENESIS; C-OXIDASE;
RHODOBACTER-SPHAEROIDES; MOLECULAR-DYNAMICS; ACTIVE-SITE; PROTON PUMP;
ELECTROSTATIC CALCULATIONS; BRADYRHIZOBIUM-JAPONICUM;
THERMUS-THERMOPHILUS
AB Heme-copper oxidases (HCOs) are terminal electron acceptors in aerobic respiration. They catalyze the reduction of molecular oxygen to water with concurrent pumping of protons across the mitochondrial and bacterial membranes. Protons required for oxygen reduction chemistry and pumping are transferred through proton uptake channels. Recently, the crystal structure of the first C-type member of the HCO superfamily was resolved [Buschmann et al. Science 329 (2010) 327-330], but crystallographic water molecules could not be identified. Here we have used molecular dynamics (MD) simulations, continuum electrostatic approaches, and quantum chemical cluster calculations to identify proton transfer pathways in cytochrome cbb(3). In MD simulations we observe formation of stable water chains that connect the highly conserved Glu323 residue on the proximal side of heme b(3) both with the N- and the P-sides of the membrane. We propose that such pathways could be utilized for redox-coupled proton pumping in the C-type oxidases. Electrostatics and quantum chemical calculations suggest an increased proton affinity of Glu323 upon reduction of high-spin heme b(3). Protonation of Glu323 provides a mechanism to tune the redox potential of heme b(3) with possible implications for proton pumping. (C) 2011 Published by Elsevier B.V.
C1 [Sharma, Vivek; Wikstrom, Marten] Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Programme Struct Biol & Biophys, FIN-00014 Helsinki, Finland.
[Kaila, Ville R. I.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Sharma, V (reprint author), Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Programme Struct Biol & Biophys, PB 65,Viikinkaari 1, FIN-00014 Helsinki, Finland.
EM vivek.sharma@helsinki.fi; marten.wikstrom@helsinki.fi;
ville.kaila@nih.gov
RI Sharma, Vivek/G-7383-2012;
OI Sharma, Vivek/0000-0002-8838-3151
FU Sigrid Juselius Foundation; Viikki Graduate School in Molecular
Biosciences; European Molecular Biology Organization (EMBO); National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases; Biocentrum Helsinki; Academy of Finland
FX V.S. is supported from Sigrid Juselius Foundation and Viikki Graduate
School in Molecular Biosciences. V.R.I.K. acknowledges the European
Molecular Biology Organization (EMBO) for a Long-Term Fellowship and the
Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases for
support. The research was supported by the Sigrid Juselius Foundation,
Biocentrum Helsinki and the Academy of Finland. The Center for
Scientific Computing (CSC), Finland, and the Biowulf cluster at NIH are
acknowledged for computing time.
NR 86
TC 8
Z9 8
U1 1
U2 22
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 MAY
PY 2012
VL 1817
IS 5
BP 726
EP 734
DI 10.1016/j.bbabio.2011.09.010
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 930YV
UT WOS:000303181800006
PM 21963365
ER
PT J
AU Haraldson, K
Kashuba, VI
Dmitriev, AA
Senchenko, VN
Kudryavtseva, AV
Pavlova, TV
Braga, EA
Pronina, IV
Kondratov, AG
Rynditch, AV
Lerman, MI
Zabarovsky, ER
AF Haraldson, Klas
Kashuba, Vladimir I.
Dmitriev, Alexey A.
Senchenko, Vera N.
Kudryavtseva, Anna V.
Pavlova, Tatiana V.
Braga, Eleonora A.
Pronina, Irina V.
Kondratov, Alexandr G.
Rynditch, Alla V.
Lerman, Michael I.
Zabarovsky, Eugene R.
TI LRRC3B gene is frequently epigenetically inactivated in several
epithelial malignancies and inhibits cell growth and replication
SO BIOCHIMIE
LA English
DT Article
DE Cancer; Tumor suppressor gene; NotI microarrays; Methylation; RT-qPCR
ID TUMOR-SUPPRESSOR GENE; DNA METHYLATION; LUNG-CANCER; PROMOTER
METHYLATION; HYPERMETHYLATION; MICROARRAYS; EXPRESSION; CARCINOMA;
DELETIONS; LEUKEMIA
AB Chromosome 3 specific NotI microarrays containing 180 NotI linking clones associated with 188 genes were hybridized to NotI representation probes prepared using matched tumor/normal samples from major epithelial cancers: breast (47 pairs), lung (40 pairs) cervical (43 pairs), kidney (34 pairs of clear cell renal cell carcinoma), colon (24 pairs), ovarian (25 pairs) and prostate (18 pairs). In all tested primary tumors (compared to normal controls) methylation and/or deletions was found. For the first time we showed that the gene LRRC3B was frequently methylated and/or deleted in breast carcinoma - 32% of samples, cervical - 35%, lung - 40%, renal - 35%, ovarian - 28%, colon - 33% and prostate cancer - 44%. To check these results bisulfite sequencing using cloned PCR products with representative two breast, one cervical, two renal, two ovarian and two colon cancer samples was performed. In all cases methylation was confirmed. Expression analysis using RT-qPCR showed that LRRC3B is strongly down-regulated at the latest stages of RCC and ovarian cancers. In addition we showed that LRRC3B exhibit strong cell growth inhibiting activity (more than 95%) in colony formation experiments in vitro in KRC/Y renal cell carcinoma line. All these data suggest that LRRC3B gene could be involved in the process of carcinogenesis as a tumor suppressor gene. (C) 2012 Elsevier Masson SAS. All rights reserved.
C1 [Haraldson, Klas; Kashuba, Vladimir I.; Dmitriev, Alexey A.; Senchenko, Vera N.; Pavlova, Tatiana V.; Zabarovsky, Eugene R.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
[Kashuba, Vladimir I.; Kondratov, Alexandr G.; Rynditch, Alla V.] Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine.
[Dmitriev, Alexey A.; Senchenko, Vera N.; Kudryavtseva, Anna V.; Zabarovsky, Eugene R.] RAS, VA Engelhardt Mol Biol Inst, Moscow 117901, Russia.
[Braga, Eleonora A.; Pronina, Irina V.] Russian State Genet Ctr, Moscow, Russia.
[Lerman, Michael I.] NIH, NHLBI, Hematol Branch, Bethesda, MD USA.
[Zabarovsky, Eugene R.] Linkoping Univ, Inst Klin & Expt Med, S-58183 Linkoping, Sweden.
RP Zabarovsky, ER (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
EM eugzab@ki.se
RI Dmitriev, Alexey/D-6109-2011; Senchenko, Vera/C-8992-2014; Kudryavtseva,
Anna/C-9032-2014; Braga, Eleonora/P-5574-2016
OI Dmitriev, Alexey/0000-0002-6827-9584; Senchenko,
Vera/0000-0002-3119-515X; Kudryavtseva, Anna/0000-0002-3722-8207;
FU Swedish Cancer Society; Swedish Institute; Swedish Research Council;
Karolinska Institute, State [02.740.11.5227, 16.552.11.7034]; Russian
Ministry of Education and Science; Russian Foundation for Basic Research
[10-04-01213-a, 11-04-00269]
FX This work was supported by research grants from the Swedish Cancer
Society, the Swedish Institute, the Swedish Research Council and
Karolinska Institute, State Contracts 02.740.11.5227 and 16.552.11.7034
with the Russian Ministry of Education and Science and by grants
10-04-01213-a and 11-04-00269 from the Russian Foundation for Basic
Research.
NR 33
TC 11
Z9 13
U1 0
U2 3
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
J9 BIOCHIMIE
JI Biochimie
PD MAY
PY 2012
VL 94
IS 5
BP 1151
EP 1157
DI 10.1016/j.biochi.2012.01.019
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 932LI
UT WOS:000303292200010
PM 22321817
ER
PT J
AU Oskvig, DB
Elkahloun, AG
Johnson, KR
Phillips, TM
Herkenham, M
AF Oskvig, Devon B.
Elkahloun, Abdel G.
Johnson, Kory R.
Phillips, Terry M.
Herkenham, Miles
TI Maternal immune activation by LPS selectively alters specific gene
expression profiles of interneuron migration and oxidative stress in the
fetus without triggering a fetal immune response
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Maternal immune activation; Inflammation; Cytokine; Lipopolysaccharide;
Schizophrenia; Autism; Microarray; Bioinformatics; Cortical
interneurons; GABA
ID AUTISM SPECTRUM DISORDERS; AUTOPHAGIC CELL-DEATH; LIPID-BINDING PROTEIN;
CORTICAL INTERNEURONS; BRAIN-DEVELOPMENT; TRANSCRIPTIONAL REGULATION;
INFLAMMATORY RESPONSE; HIPPOCAMPAL-NEURONS; PRENATAL INFECTION;
ALPHA-HEMOGLOBIN
AB Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism. Published by Elsevier Inc.
C1 [Oskvig, Devon B.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NIH, Div Intramural Res Programs, Microarray Core Facil, Bethesda, MD 20892 USA.
[Johnson, Kory R.] Natl Inst Neurol Disorders & Stroke, Bioinformat Sect, NIH, Bethesda, MD 20892 USA.
[Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Section, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Herkenham, M (reprint author), Bldg 35,Rm 1C913, Bethesda, MD 20892 USA.
EM herkenh@mail.nih.gov
OI Herkenham, Miles/0000-0003-2228-4238
FU National Institute of Mental Health, NIH
FX The research was supported by the Intramural Research Program, National
Institute of Mental Health, NIH.
NR 115
TC 44
Z9 46
U1 3
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD MAY
PY 2012
VL 26
IS 4
BP 623
EP 634
DI 10.1016/j.bbi.2012.01.015
PG 12
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 929PV
UT WOS:000303078800016
PM 22310921
ER
PT J
AU Johannesdottir, F
Aspelund, T
Siggeirsdottir, K
Jonsson, BY
Mogensen, B
Sigurdsson, S
Harris, TB
Gudnason, VG
Lang, TF
Sigurdsson, G
AF Johannesdottir, Fjola
Aspelund, Thor
Siggeirsdottir, Kristin
Jonsson, Brynjolfur Y.
Mogensen, Brynjolfur
Sigurdsson, Sigurdur
Harris, Tamara B.
Gudnason, Vilmundur G.
Lang, Thomas F.
Sigurdsson, Gunnar
TI Mid-Thigh Cortical Bone Structural Parameters, Muscle Mass and Strength,
and Association with Lower Limb Fractures in Older Men and Women
(AGES-Reykjavik Study)
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE Mid-thigh; Muscle-bone relationship; Aging; Fracture risk; CT
ID MINERAL DENSITY; TRABECULAR BONE; ELDERLY-MEN; POSTMENOPAUSAL WOMEN;
WHOLE-BODY; LOWER LEG; HIP; ADULTS; EXERCISE; HEALTH
AB In a cross-sectional study we investigated the relationship between muscle and bone parameters in the mid-thigh in older people using data from a single axial computed tomographic section through the mid-thigh. Additionally, we studied the association of these variables with incident low-trauma lower limb fractures. A total of 3,762 older individuals (1,838 men and 1,924 women), aged 66-96 years, participants in the AGES-Reykjavik study, were studied. The total cross-sectional muscular area and knee extensor strength declined with age similarly in both sexes. Muscle parameters correlated most strongly with cortical area and total shaft area (adjusted for age, height, and weight) but explained < 10 % of variability in those bone parameters. The increment in medullary area (MA) and buckling ratio (BR) with age was almost fourfold greater in women than men. The association between MA and muscle parameters was nonsignificant. During a median follow-up of 5.3 years, 113 women and 66 men sustained incident lower limb fractures. Small muscular area, low knee extensor strength, large MA, low cortical thickness, and high BR were significantly associated with fractures in both sexes. Our results show that bone and muscle loss proceed at different rates and with different gender patterns.
C1 [Mogensen, Brynjolfur; Sigurdsson, Gunnar] Landspitali Univ Hosp, IS-108 Reykjavik, Iceland.
[Aspelund, Thor; Siggeirsdottir, Kristin; Sigurdsson, Sigurdur; Gudnason, Vilmundur G.; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland.
[Jonsson, Brynjolfur Y.] Malmo Univ Hosp, Malmo, Sweden.
[Johannesdottir, Fjola; Aspelund, Thor; Mogensen, Brynjolfur; Gudnason, Vilmundur G.; Sigurdsson, Gunnar] Univ Iceland, Reykjavik, Iceland.
[Harris, Tamara B.] Natl Inst Aging, Bethesda, MD USA.
[Lang, Thomas F.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Sigurdsson, G (reprint author), Landspitali Univ Hosp, IS-108 Reykjavik, Iceland.
EM gunnars@landspitali.is
RI Lang, Thomas/B-2685-2012; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Lang, Thomas/0000-0002-3720-8038; Aspelund, Thor/0000-0002-7998-5433;
Gudnason, Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-1-2100]; NIA; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); memorial fund of Helga Jonsdottir
and Sigurlidi Kristjansson; University of Iceland
FX This study was funded by NIH contract N01-AG-1-2100, the NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), the
Althingi (the Icelandic Parliament), and the memorial fund of Helga
Jonsdottir and Sigurlidi Kristjansson. G.S. acknowledges support from
the University of Iceland Research Fund. The study was approved by the
Icelandic National Bioethics Committee (VSN 00-063). The researchers are
indebted to the participants for their willingness to participate in the
study.
NR 45
TC 15
Z9 15
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-967X
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD MAY
PY 2012
VL 90
IS 5
BP 354
EP 364
DI 10.1007/s00223-012-9585-6
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 928VX
UT WOS:000303017300002
PM 22451219
ER
PT J
AU Eheman, C
Henley, SJ
Ballard-Barbash, R
Jacobs, EJ
Schymura, MJ
Noone, AM
Pan, LP
Anderson, RN
Fulton, JE
Kohler, BA
Jemal, A
Ward, E
Plescia, M
Ries, LAG
Edwards, BK
AF Eheman, Christie
Henley, S. Jane
Ballard-Barbash, Rachel
Jacobs, Eric J.
Schymura, Maria J.
Noone, Anne-Michelle
Pan, Liping
Anderson, Robert N.
Fulton, Janet E.
Kohler, Betsy A.
Jemal, Ahmedin
Ward, Elizabeth
Plescia, Marcus
Ries, Lynn A. G.
Edwards, Brenda K.
TI Annual Report to the Nation on the status of cancer, 1975-2008,
featuring cancers associated with excess weight and lack of sufficient
physical activity
SO CANCER
LA English
DT Editorial Material
DE cancer; incidence; mortality; Surveillance; Epidemiology; and End
Results; the North American Association of Central Cancer Registries;
National Program of Cancer Registries; United States; obesity; physical
inactivity
ID BODY-MASS INDEX; UNITED-STATES; COLORECTAL-CANCER; BREAST-CANCER;
CHILDHOOD OBESITY; INCIDENCE RATES; COLON-CANCER; RISK-FACTORS;
LUNG-CANCER; EPIDEMIOLOGIC EVIDENCE
AB BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through collaboration between the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This year's report highlights the increased cancer risk associated with excess weight (overweight or obesity) and lack of sufficient physical activity (<150 minutes of physical activity per week). METHODS: Data on cancer incidence were obtained from the CDC, NCI, and NAACCR; data on cancer deaths were obtained from the CDC's National Center for Health Statistics. Annual percent changes in incidence and death rates (age-standardized to the 2000 US population) for all cancers combined and for the leading cancers among men and among women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2008 and mortality for 1975-2008) and short-term trends (1999-2008). Information was obtained from national surveys about the proportion of US children, adolescents, and adults who are overweight, obese, insufficiently physically active, or physically inactive. RESULTS: Death rates from all cancers combined decreased from 1999 to 2008, continuing a decline that began in the early 1990s, among men and among women in most racial and ethnic groups. Death rates decreased from 1999 to 2008 for most cancer sites, including the 4 most common cancers (lung, colorectum, breast, and prostate). The incidence of prostate and colorectal cancers also decreased from 1999 to 2008. Lung cancer incidence declined from 1999 to 2008 among men and from 2004 to 2008 among women. Breast cancer incidence decreased from 1999 to 2004 but was stable from 2004 to 2008. Incidence increased for several cancers, including pancreas, kidney, and adenocarcinoma of the esophagus, which are associated with excess weight. CONCLUSIONS: Although improvements are reported in the US cancer burden, excess weight and lack of sufficient physical activity contribute to the increased incidence of many cancers, adversely affect quality of life for cancer survivors, and may worsen prognosis for several cancers. The current report highlights the importance of efforts to promote healthy weight and sufficient physical activity in reducing the cancer burden in the United States.* Cancer 2012; 118: 2338-66. (C) 2012 American Cancer Society.
C1 [Eheman, Christie; Henley, S. Jane; Plescia, Marcus] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Ballard-Barbash, Rachel; Noone, Anne-Michelle; Ries, Lynn A. G.; Edwards, Brenda K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Jacobs, Eric J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Schymura, Maria J.; Kohler, Betsy A.] N Amer Assoc Cent Canc Registries, Springfield, IL USA.
[Schymura, Maria J.] New York State Canc Registry, Albany, NY USA.
[Pan, Liping; Fulton, Janet E.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Anderson, Robert N.] Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Atlanta, GA 30341 USA.
[Jemal, Ahmedin; Ward, Elizabeth] Amer Canc Soc, Surveillance & Hlth Policy Res Dept, Atlanta, GA 30329 USA.
RP Eheman, C (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,Mailstop F-69, Atlanta, GA 30341 USA.
EM cre1@cdc.gov
OI Henley, S Jane/0000-0002-2420-306X
FU Intramural CDC HHS [CC999999]
NR 134
TC 212
Z9 223
U1 11
U2 57
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAY 1
PY 2012
VL 118
IS 9
BP 2338
EP 2366
DI 10.1002/cncr.27514
PG 29
WC Oncology
SC Oncology
GA 929ES
UT WOS:000303044600003
PM 22460733
ER
PT J
AU Suh, KS
Malik, M
Shukla, A
Ryscavage, A
Wright, L
Jividen, K
Crutchley, JM
Dumont, RA
Fernandez-Salas, E
Webster, JD
Simpson, RM
Yuspa, SH
AF Suh, K. Stephen
Malik, Mariam
Shukla, Anjali
Ryscavage, Andrew
Wright, Lisa
Jividen, Kasey
Crutchley, John M.
Dumont, Rebecca A.
Fernandez-Salas, Ester
Webster, Joshua D.
Simpson, R. Mark
Yuspa, Stuart H.
TI CLIC4 is a tumor suppressor for cutaneous squamous cell cancer
SO CARCINOGENESIS
LA English
DT Article
ID CHLORIDE CHANNEL PROTEIN; ION-CHANNEL; NUCLEAR TRANSLOCATION; PROTEOMIC
ANALYSIS; INDUCED APOPTOSIS; CRYSTAL-STRUCTURE; REDOX REGULATION;
GENE-EXPRESSION; STEM-CELLS; DIFFERENTIATION
AB Chloride intracellular channel (CLIC) 4 is a member of a redox-regulated, metamorphic multifunctional protein family, first characterized as intracellular chloride channels. Current knowledge indicates that CLICs participate in signaling, cytoskeleton integrity and differentiation functions of multiple tissues. In metabolically stressed skin keratinocytes, cytoplasmic CLIC4 is S-nitrosylated and translocates to the nucleus where it enhances transforming growth factor-beta (TGF-beta) signaling by protecting phospho-Smad 2 and 3 from dephosphorylation. CLIC4 expression is diminished in multiple human epithelial cancers, and the protein is excluded from the nucleus. We now show that CLIC4 expression is reduced in chemically induced mouse skin papillomas, mouse and human squamous carcinomas and squamous cancer cell lines, and the protein is excluded from the nucleus. The extent of reduction in CLIC4 coincides with progression of squamous tumors from benign to malignant. Inhibiting antioxidant defense in tumor cells increases S-nitrosylation and nuclear translocation of CLIC4. Adenoviral-mediated reconstitution of nuclear CLIC4 in squamous cancer cells enhances TGF-beta-dependent transcriptional activity and inhibits growth. Adenoviral targeting of CLIC4 to the nucleus of tumor cells in orthografts inhibits tumor growth, whereas elevation of CLIC4 in transgenic epidermis reduces de novo chemically induced skin tumor formation. In parallel, overexpression of exogenous CLIC4 in squamous tumor orthografts suppresses tumor growth and enhances TGF-beta signaling. These results indicate that CLIC4 suppresses the growth of squamous cancers, that reduced CLIC4 expression and nuclear residence detected in cancer cells is associated with the altered redox state of tumor cells and the absence of detectable nuclear CLIC4 in cancers contributes to TGF-beta resistance and enhances tumor development.
C1 [Suh, K. Stephen; Malik, Mariam; Shukla, Anjali; Ryscavage, Andrew; Wright, Lisa; Jividen, Kasey; Crutchley, John M.; Dumont, Rebecca A.; Fernandez-Salas, Ester; Webster, Joshua D.; Simpson, R. Mark; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
RI Shukla, Anjali/G-4046-2014;
OI Jividen, Kasey/0000-0003-1022-5038
FU Center for Cancer Research, National Cancer Institute, USA
FX This work was supported by the Intramural research program of the Center
for Cancer Research, National Cancer Institute, USA.
NR 50
TC 10
Z9 12
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAY
PY 2012
VL 33
IS 5
BP 986
EP 995
DI 10.1093/carcin/bgs115
PG 10
WC Oncology
SC Oncology
GA 933DE
UT WOS:000303338800006
PM 22387366
ER
PT J
AU Barnes, KA
Nelson, SM
Cohen, AL
Power, JD
Coalson, RS
Miezin, FM
Vogel, AC
Dubis, JW
Church, JA
Petersen, SE
Schlaggar, BL
AF Barnes, Kelly Anne
Nelson, Steven M.
Cohen, Alexander L.
Power, Jonathan D.
Coalson, Rebecca S.
Miezin, Francis M.
Vogel, Alecia C.
Dubis, Joseph W.
Church, Jessica A.
Petersen, Steven E.
Schlaggar, Bradley L.
TI Parcellation in Left Lateral Parietal Cortex Is Similar in Adults and
Children
SO CEREBRAL CORTEX
LA English
DT Article
DE brain development; functional areas; functional connectivity; parietal
lobe
ID HUMAN CEREBRAL-CORTEX; BRAIN-DEVELOPMENT; WORKING-MEMORY; VISUAL-CORTEX;
STRUCTURAL CONNECTIVITY; DEVELOPMENTAL-CHANGES; ADOLESCENT BRAIN;
CORTICAL AREAS; DEFAULT MODE; NETWORKS
AB A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.
C1 [Barnes, Kelly Anne; Cohen, Alexander L.; Power, Jonathan D.; Coalson, Rebecca S.; Miezin, Francis M.; Vogel, Alecia C.; Dubis, Joseph W.; Church, Jessica A.; Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
[Nelson, Steven M.; Petersen, Steven E.] Washington Univ, Dept Psychol, St Louis, MO 63110 USA.
[Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Dept Radiol, St Louis, MO 63110 USA.
[Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Schlaggar, Bradley L.] Washington Univ, Dept Pediat, St Louis, MO 63110 USA.
RP Barnes, KA (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA.
EM kelly.barnes@nih.gov
RI Cohen, Alexander/A-6865-2009; Church, Jessica/L-2659-2016
OI Cohen, Alexander/0000-0001-6557-5866; Church,
Jessica/0000-0003-1369-9116
FU National Institutes of Health [NS007205-28, NS062489, NS053425,
HD057076, MH091512, NS06114, NS046424]; Simons Foundation Autism
Research Initiative
FX National Institutes of Health (grants NS007205-28 to K. A. B., NS062489
to A. L. C., NS053425, HD057076, and MH091512 to B. L. S., and NS06114
and NS046424 to S. E. P.); Simons Foundation Autism Research Initiative.
NR 67
TC 18
Z9 18
U1 2
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD MAY
PY 2012
VL 22
IS 5
BP 1148
EP 1158
DI 10.1093/cercor/bhr189
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 930SX
UT WOS:000303161400017
PM 21810781
ER
PT J
AU Mugnaini, C
Nocerino, S
Pedani, V
Pasquini, S
Tafi, A
De Chiaro, M
Bellucci, L
Valoti, M
Guida, F
Luongo, L
Dragoni, S
Ligresti, A
Rosenberg, A
Bolognini, D
Cascio, MG
Pertwee, RG
Moaddel, R
Maione, S
Di Marzo, V
Corelli, F
AF Mugnaini, Claudia
Nocerino, Stefania
Pedani, Valentina
Pasquini, Serena
Tafi, Andrea
De Chiaro, Maria
Bellucci, Luca
Valoti, Massimo
Guida, Francesca
Luongo, Livio
Dragoni, Stefania
Ligresti, Alessia
Rosenberg, Avraham
Bolognini, Daniele
Cascio, Maria Grazia
Pertwee, Roger G.
Moaddel, Ruin
Maione, Sabatino
Di Marzo, Vincenzo
Corelli, Federico
TI Investigations on the 4-Quinolone-3-Carboxylic Acid Motif Part 5:
Modulation of the Physicochemical Profile of a Set of Potent and
Selective Cannabinoid-2 Receptor Ligands through a Bioisosteric Approach
SO CHEMMEDCHEM
LA English
DT Article
DE bioisosteres; cannabinoids; quinolones; receptors; structure-activity
relationships
ID PHARMACOLOGICALLY ACTIVE METABOLITES; ENERGY DECOMPOSITION; DRUG
DISCOVERY; CB2 RECEPTORS; IN-VIVO; MOLECULAR-INTERACTIONS; MICROWAVE
IRRADIATION; ANTICANCER AGENTS; NEUROPATHIC PAIN; FORMALIN TEST
AB Three heterocyclic systems were selected as potential bioisosteres of the amide linker for a series of 1,6-disubstituted-4-quinolone-3-carboxamides, which are potent and selective CB2 ligands that exhibit poor water solubility, with the aim of improving their physicochemical profile and also of clarifying properties of importance for amide bond mimicry. Among the newly synthesized compounds, a 1,2,3-triazole derivative (1-(adamantan-1-yl)-4-[6-(furan-2-yl)-1,4-dihydro-4-oxo-1-pentylquinolin-3-yl]-1H-1,2,3-triazole) emerged as the most promising in terms of both physicochemical and pharmacodynamic properties. When assayed in vitro, this derivative exhibited inverse agonist activity, whereas, in the formalin test in mice, it produced analgesic effects antagonized by a well-established inverse agonist. Metabolic studies allowed the identification of a side chain hydroxylated derivative as its only metabolite, which, in its racemic form, still showed appreciable CB2 selectivity, but was 150-fold less potent than the parent compound.
C1 [Mugnaini, Claudia; Nocerino, Stefania; Pedani, Valentina; Pasquini, Serena; Tafi, Andrea; Bellucci, Luca; Corelli, Federico] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy.
[Valoti, Massimo; Dragoni, Stefania] Univ Siena, Dipartimento Neurosci, Sez Farmacol, I-53100 Siena, Italy.
[Ligresti, Alessia; Di Marzo, Vincenzo] CNR, Ist Chim Biomol, Endocannabinoid Res Grp, I-80078 Naples, Italy.
[De Chiaro, Maria; Guida, Francesca; Luongo, Livio; Maione, Sabatino] Univ Naples 2, Dipartimento Med Sperimentale, I-80138 Naples, Italy.
[Rosenberg, Avraham; Moaddel, Ruin] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Bolognini, Daniele; Cascio, Maria Grazia; Pertwee, Roger G.] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
RP Mugnaini, C (reprint author), Univ Siena, Dipartimento Farmaco Chim Tecnol, Via De Gasperi 2, I-53100 Siena, Italy.
EM claudia.mugnaini@unisi.it; federico.corelli@unisi.it
RI Ligresti, Alessia/B-7564-2015;
OI Luongo, Livio/0000-0002-1949-2039; Pertwee, Roger/0000-0003-3227-2783
FU US National Institute on Aging; US National Institutes of Health (NIH)
[DA-03672]
FX A.L. and V.D.M. thank Mr. Marco Allara (CNR, Pozzuoli, Italy) for
technical assistance. R.M. and A.R. thank the Intramural Research
Program of the US National Institute on Aging for financial support.
D.B., M.G.C. and R.G.P. thank the US National Institutes of Health (NIH)
for funding (grant no.: DA-03672).
NR 73
TC 11
Z9 11
U1 1
U2 16
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 MAY
PY 2012
VL 7
IS 5
BP 920
EP 934
DI 10.1002/cmdc.201100573
PG 15
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 931CP
UT WOS:000303192300018
PM 22383251
ER
PT J
AU Jia, LB
AF Jia, Libin
TI Cancer Complementary and Alternative Medicine Research at the US
National Cancer Institute
SO CHINESE JOURNAL OF INTEGRATIVE MEDICINE
LA English
DT Editorial Material
DE complementary and alternative medicine; Chinese medicine; cancer
research
ID PANCREATIC-CANCER; STEM-CELLS; EXPRESSION; CARCINOMA; 6-SHOGAOL; PHY906;
MICE
AB The United States National Cancer Institute (NCI) supports complementary and alternative medicine (CAM) research which includes different methods and practices (such as nutrition therapies) and other medical systems (such as Chinese medicine). In recent years, NCI has spent around $120 million each year on various CAM-related research projects on cancer prevention, treatment, symptom/side effect management and epidemiology. The categories of CAM research involved include nutritional therapeutics, pharmacological and biological treatments, mind-body interventions, manipulative and body based methods, alternative medical systems, exercise therapies, spiritual therapies and energy therapies on a range of types of cancer. The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) supports various intramural and extramural cancer CAM research projects. Examples of these cancer CAM projects are presented and discussed. In addition, OCCAM also supports international research projects.
C1 NCI, Off Canc Complementary & Alternat Med, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Jia, LB (reprint author), NCI, Off Canc Complementary & Alternat Med, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
EM libinj@mail.nih.gov
NR 20
TC 13
Z9 13
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1672-0415
J9 CHIN J INTEGR MED
JI Chin. J. Integr. Med.
PD MAY
PY 2012
VL 18
IS 5
BP 325
EP 332
DI 10.1007/s11655-011-0950-5
PG 8
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 933LD
UT WOS:000303362100002
PM 22241505
ER
PT J
AU Fan, XY
Upadhyaya, B
Wu, LM
Koh, C
Santin-Duran, M
Pittaluga, S
Uzel, G
Kleiner, D
Williams, E
Ma, CA
Bodansky, A
Oliveira, JB
Edmonds, P
Hornung, R
Wong, DW
Fayer, R
Fleisher, T
Heller, T
Prussin, C
Jain, A
AF Fan, Xiying
Upadhyaya, Bhaskar
Wu, Liming
Koh, Christopher
Santin-Duran, Monica
Pittaluga, Stefania
Uzel, Gulbu
Kleiner, David
Williams, Ester
Ma, Chi A.
Bodansky, Aaron
Oliveira, Joao B.
Edmonds, Pamela
Hornung, Ronald
Wong, Duane W.
Fayer, Ronald
Fleisher, Tom
Heller, Theo
Prussin, Calman
Jain, Ashish
TI CD40 agonist antibody mediated improvement of chronic Cryptosporidium
infection in patients with X-linked hyper IgM syndrome
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE X-linked hyper-IgM syndrome; CD40 ligand; CP-870,893; CD40-R
internalization
ID DENDRITIC CELLS; CD40-CD40L INTERACTIONS; IMMUNOLOGICAL FEATURES;
T-CELLS; PHASE-I; LIGAND; MICE; ACTIVATION; IMMUNODEFICIENCY; DEFICIENCY
AB X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist monoclonal antibody, in the treatment of two XHM patients with biliary Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restoring class switch recombination in XHM B cells and inducing cytokine secretion by monocytes. CP-870,893 infusions were well tolerated and showed significant activity in vivo, decreasing leukocyte concentration in peripheral blood. Although specific antibody responses were lacking, frequent dosing in one subject primed T cells to secrete IFN-g and suppressed oocyst shedding in the stool. Nevertheless, relapse occurred after discontinuation of therapy. The CD40 receptor was rapidly internalized following binding with CP-870,893, potentially explaining the limited capacity of CP-870,893 to mediate immune reconstitution. This study demonstrates that CP-870,893 suppressed oocysts shedding in XHM patients with biliary cryptosporidiosis. The continued study of CD40 agonists in XHM is warranted. Published by Elsevier Inc.
C1 [Fan, Xiying; Wu, Liming; Ma, Chi A.; Bodansky, Aaron; Edmonds, Pamela; Jain, Ashish] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Upadhyaya, Bhaskar; Prussin, Calman] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Williams, Ester; Oliveira, Joao B.; Fleisher, Tom] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Kleiner, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wong, Duane W.] Arizona Allergy Associates, Phoenix, AZ USA.
[Hornung, Ronald] NCI, SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21701 USA.
[Santin-Duran, Monica; Fayer, Ronald] USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA.
RP Jain, A (reprint author), NIAID, Lab Host Def, NIH, 10 Ctr Dr,Rm 5W 3950, Bethesda, MD 20892 USA.
EM ajain@nih.gov
OI Oliveira, Joao/0000-0001-9388-8173; Prussin, Calman/0000-0002-3917-3326;
Fan, Xiying/0000-0003-3090-381X; Kleiner, David/0000-0003-3442-4453
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
NIAID/NIH
FX The 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, and supported by the intramural program of
NIAID/NIH.
NR 38
TC 8
Z9 9
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD MAY
PY 2012
VL 143
IS 2
BP 152
EP 161
DI 10.1016/j.clim.2012.01.014
PG 10
WC Immunology
SC Immunology
GA 932KV
UT WOS:000303290900006
PM 22459705
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Conservative handling of missing data
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Letter
DE Incentives; ITT; LOCF; Missing at random; Worst rank analysis
ID CLINICAL-TRIALS
C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
[Berger, Vance W.] UMBC, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
NR 3
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAY
PY 2012
VL 33
IS 3
BP 460
EP 460
DI 10.1016/j.cct.2012.02.008
PG 1
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 930XM
UT WOS:000303178100002
PM 22366777
ER
PT J
AU Legro, RS
Kunselman, AR
Brzyski, RG
Casson, PR
Diamond, MP
Schlaff, WD
Christman, GM
Coutifaris, C
Taylor, HS
Eisenberg, E
Santoro, N
Zhang, HP
AF Legro, Richard S.
Kunselman, Allen R.
Brzyski, Robert G.
Casson, Peter R.
Diamond, Michael P.
Schlaff, William D.
Christman, Gregory M.
Coutifaris, Christos
Taylor, Hugh S.
Eisenberg, Esther
Santoro, Nanette
Zhang, Heping
CA NICHD Reprod Med Network
TI The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial:
Rationale and design of a double-blind randomized trial of clomiphene
citrate and letrozole for the treatment of infertility in women with
polycystic ovary syndrome
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Polycystic Ovary Syndrome; Infertility; Ovulation induction;
Hyperandrogenism; Clomiphene citrate; Letrozole
ID QUALITY-OF-LIFE; GENERAL PSYCHOMETRIC PROPERTIES; ADAPALENE GEL
0.3-PERCENT; FERTIQOL TOOL DEVELOPMENT; IN-VITRO FERTILIZATION;
SURROGATE END-POINTS; ACNE-VULGARIS; OVULATION INDUCTION; AROMATASE
INHIBITOR; INSULIN-RESISTANCE
AB Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50 mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5 mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (x5 days) or 7.5 mg of letrozole a day (x5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Legro, Richard S.] Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Penn State Coll Med, Hershey, PA 17033 USA.
[Kunselman, Allen R.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
[Casson, Peter R.] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT USA.
[Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
[Christman, Gregory M.] Univ Michigan, Dept Obstet, Ann Arbor, MI 48109 USA.
[Christman, Gregory M.] Univ Michigan, Dept Gynecol, Ann Arbor, MI 48109 USA.
[Coutifaris, Christos] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Taylor, Hugh S.] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA.
[Eisenberg, Esther] Eunice Kennedy Shriver NICHD, Reprod Sci Branch, Rockville, MD USA.
[Zhang, Heping] Yale Univ, Sch Med, Dept Biostat, New Haven, CT USA.
RP Legro, RS (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Penn State Coll Med, 500 Univ Dr,H103, Hershey, PA 17033 USA.
EM rsl1@psu.edu
OI Diamond, Michael/0000-0001-6353-4489
FU National Institutes of Health (NIH)/Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) [U10 HD27049,
U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10
HD055936, U10 HD055942, U10 HD055944, U54-HD29834]; National Institutes
of Health (NIH)/Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), General Clinical Research Center
[MO1RR10732, C06 RR016499]
FX This work was supported by National Institutes of Health (NIH)/Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) Grants U10 HD27049 (to C.C.); U10 HD38992 (to R.S.L.);
U10HD055925 (to H.Z.); U10 HD39005 (to M.P.D.); U10 HD33172 (to M.P.S.);
U10 HD38998 (to W.D.S); U10 HD055936 (to G.M.C.); U10 HD055942 (to
R.G.B.); and U10 HD055944 (to P.R.C.); U54-HD29834 (to the University of
Virginia Center for Research in Reproduction Ligand Assay and Analysis
Core of the Specialized Cooperative Centers Program in Reproduction and
Infertility Research); General Clinical Research Center Grants
MO1RR10732 and construction grant C06 RR016499 (to Pennsylvania State
University). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NICHD or NIH.
NR 48
TC 24
Z9 26
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAY
PY 2012
VL 33
IS 3
BP 470
EP 481
DI 10.1016/j.cct.2011.12.005
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 930XM
UT WOS:000303178100004
PM 22265923
ER
PT J
AU Brache, V
Sitruk-Ware, R
Williams, A
Blithe, D
Croxatto, H
Kumar, N
Kumar, S
Tsong, YY
Sivin, I
Nath, A
Sussman, H
Cochon, L
Miranda, MJ
Reyes, V
Faundes, A
Mishell, D
AF Brache, Vivian
Sitruk-Ware, Regine
Williams, Alistair
Blithe, Diana
Croxatto, Horacio
Kumar, Narender
Kumar, Sushma
Tsong, Yun-Yen
Sivin, Irving
Nath, Anita
Sussman, Heather
Cochon, Leila
Jose Miranda, Maria
Reyes, Veronica
Faundes, Anibal
Mishell, Daniel, Jr.
TI Effects of a novel estrogen-free, progesterone receptor modulator
contraceptive vaginal ring on inhibition of ovulation, bleeding patterns
and endometrium in normal women
SO CONTRACEPTION
LA English
DT Article
DE Progesterone receptor modulators; Ulipristal acetate; Contraceptive
vaginal ring; Ovulation inhibition; Follicular development;
PRM-associated endometrial changes
ID RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE MIFEPRISTONE; ULIPRISTAL ACETATE;
EMERGENCY CONTRACEPTION; DOUBLE-BLIND; CDB-2914; ANTIPROGESTINS;
ANTAGONISTS; LEVONORGESTREL; ESTRADIOL
AB Background: Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation.
Study Design: This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated.
Results: Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of ill "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%).
Conclusion: In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Brache, Vivian] Profamilia, Biomed Res Dept, Santo Domingo 10401, Dominican Rep.
[Sitruk-Ware, Regine; Kumar, Narender; Kumar, Sushma; Tsong, Yun-Yen; Sivin, Irving; Nath, Anita; Sussman, Heather] Populat Council, Ctr Biomed Res, New York, NY 10017 USA.
[Williams, Alistair] Univ Edinburgh, Dept Pathol, Edinburgh EH16 4SA, Midlothian, Scotland.
[Blithe, Diana] Natl Inst Child Hlth & Human Dev NICHD, NIH, Bethesda, MD 20892 USA.
[Croxatto, Horacio] Univ Santiago Chile, Santiago 32349, Chile.
[Jose Miranda, Maria; Reyes, Veronica] Inst Chileno Med Reprod ICMER, Santiago 8320165, Chile.
[Mishell, Daniel, Jr.] Univ So Calif, Keck Sch Med, Dept Ob Gyn, Los Angeles, CA 90033 USA.
RP Brache, V (reprint author), Profamilia, Biomed Res Dept, POB 1053, Santo Domingo 10401, Dominican Rep.
EM vbrache@gmail.com
OI Williams, Alistair/0000-0002-7085-4525
FU National Institute of Child Health and Human Development of the National
Institutes of Health [U54 HD 29990]
FX This study was supported by a grant from the National Institute of Child
Health and Human Development of the National Institutes of Health (grant
number U54 HD 29990). The authors would like to thank HRA Pharma, Paris,
France, for supplying ulipristal acetate for the study.
NR 35
TC 18
Z9 18
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0010-7824
J9 CONTRACEPTION
JI Contraception
PD MAY
PY 2012
VL 85
IS 5
BP 480
EP 488
DI 10.1016/j.contraception.2011.10.003
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 931AX
UT WOS:000303187500010
PM 22176795
ER
PT J
AU Rice, TW
Rubinson, L
Uyeki, TM
Vaughn, FL
John, BB
Miller, RR
Higgs, E
Randolph, AG
Smoot, BE
Thompson, BT
AF Rice, Todd W.
Rubinson, Lewis
Uyeki, Timothy M.
Vaughn, Frances L.
John, Benjamin B.
Miller, Russell R., II
Higgs, Elizabeth
Randolph, Adrienne G.
Smoot, B. Elizabeth
Thompson, B. Taylor
CA NHLBI ARDS Network
TI Critical illness from 2009 pandemic influenza A virus and bacterial
coinfection in the United States
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE bacterial coinfection; critical illness; mortality; pandemic H1N1
influenza
ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY
PRESSURE; H1N1 VIRUS; A(H1N1) INFECTION; ILL PATIENTS; VENTILATION;
PNEUMONIA; FAILURE; MEXICO
AB Objectives: The contribution of bacterial coinfection to critical illness associated with 2009 influenza A virus infection remains uncertain. The objective of this study was to determine whether bacterial coinfection increased the morbidity and mortality of 2009 influenza A.
Design: Retrospective and prospective cohort study.
Setting: Thirty-five adult U. S. intensive care units over the course of 1 yr.
Patients: Six hundred eighty-three critically ill adults with confirmed or probable 2009 influenza A.
Interventions: None.
Measurements and Main Results: A confirmed or probable case was defined as a positive 2009 influenza A test result or positive test for influenza A that was otherwise not subtyped. Bacterial coinfection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hrs of intensive care unit admission. The mean age was 45 +/- 16 yrs, mean body mass index was 32.5 +/- 11.1 kg/m(2), and mean Acute Physiology and Chronic Health Examination II score was 21 +/- 9, with 76% having at least one comorbidity. Of 207 (30.3%) patients with bacterial coinfection on intensive care unit admission, 154 had positive cultures with Staphylococcus aureus (n = 57) and Streptococcus pneumoniae (n = 19), the most commonly identified pathogens. Bacterial coinfected patients were more likely to present with shock (21% vs. 10%; p = .0001), require mechanical ventilation at the time of intensive care unit admission (63% vs. 52%; p = .005), and have longer duration of intensive care unit care (median, 7 vs. 6 days; p = .05). Hospital mortality was 23%; 31% in bacterial coinfected patients and 21% in patients without coinfection (p = .002). Immunosuppression (relative risk 1.57; 95% confidence interval 1.20-2.06; p = .0009) and Staphylococcus aureus at admission (relative risk 2.82; 95% confidence interval 1.76-4.51; p < .0001) were independently associated with increased mortality.
Conclusions: Among intensive care unit patients with 2009 influenza A, bacterial coinfection diagnosed within 72 hrs of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality. (Crit Care Med 2012; 40: 1487-1498)
C1 [Rice, Todd W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Rubinson, Lewis] HHS ASPR OPEO, Natl Disaster Med Syst, Salt Lake City, UT USA.
[Uyeki, Timothy M.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Salt Lake City, UT USA.
[Vaughn, Frances L.; John, Benjamin B.] HHS ASPR OPEO, Emergency Care Coordinat Ctr, Salt Lake City, UT USA.
[Miller, Russell R., II] Intermt Med Ctr, Salt Lake City, UT USA.
[Miller, Russell R., II] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Higgs, Elizabeth] NIAID, Div Clin Res, NIH, Boston, MA USA.
[Randolph, Adrienne G.] Childrens Hosp, Boston, MA 02115 USA.
[Smoot, B. Elizabeth] Harvard Univ, Sch Med, Boston, MA USA.
[Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Rice, TW (reprint author), Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
EM todd.rice@vanderbilt.edu
OI Randolph, Adrienne/0000-0002-3084-3071
FU NHLBI [N01-HR-56179]
FX Supported, in part, by NHLBI N01-HR-56179.
NR 35
TC 66
Z9 72
U1 2
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAY
PY 2012
VL 40
IS 5
BP 1487
EP 1498
DI 10.1097/CCM.0b013e3182416f23
PG 12
WC Critical Care Medicine
SC General & Internal Medicine
GA 930AE
UT WOS:000303106900012
PM 22511131
ER
PT J
AU Chertow, DS
AF Chertow, Daniel S.
TI Contribution of bacterial coinfection to severe influenza infection
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE bacteria; coinfection; critical illness; influenza; pathogenesis
ID PANDEMIC INFLUENZA; PNEUMONIA; VIRUS; ILLNESS
C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Chertow, DS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 16
TC 3
Z9 3
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAY
PY 2012
VL 40
IS 5
BP 1664
EP 1665
DI 10.1097/CCM.0b013e3182451fd8
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 930AE
UT WOS:000303106900042
PM 22511151
ER
PT J
AU Singer, EA
Kaushal, A
Turkbey, B
Couvillon, A
Pinto, PA
Parnes, HL
AF Singer, Eric A.
Kaushal, Aradhana
Turkbey, Baris
Couvillon, Anna
Pinto, Peter A.
Parnes, Howard L.
TI Active surveillance for prostate cancer: past, present and future
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE active surveillance; focal ablation; multiparametric MRI; prostate
cancer; prostate-specific antigen; screening; watchful waiting
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; RADICAL PROSTATECTOMY;
FOLLOW-UP; INITIAL TREATMENT; SCREENING TRIAL; BIOPSY; MEN; MORTALITY;
ANTIGEN
AB Purpose of review
This article reviews recent developments in the use of active surveillance for localized prostate cancer.
Recent findings
The treatment of localized prostate cancer continues to be a major challenge for urologic oncologists. Screening with prostate-specific antigen has resulted in increased numbers of low-risk prostate cancers being detected. Aggressive whole-gland therapy with surgery, or radiation therapy is associated with potentially life-altering treatment-related side effects such as urinary incontinence, bowel toxicity and erectile dysfunction. The goal of active surveillance is to avoid or delay the adverse events associated with prostate cancer therapy while still allowing for curative intervention in the future, if needed.
Summary
Active surveillance is a reasonable treatment option for many men with low-risk, and some men with intermediate-risk, prostate cancer. Additional research is needed to determine the optimal active surveillance inclusion criteria, monitoring schedule, and treatment triggers. It is hoped that advances in prostate imaging, biomarkers, and focal therapy will foster greater use of active surveillance in appropriately selected men to optimize quality-of-life without compromising cancer outcomes.
C1 [Parnes, Howard L.] NCI, Res Grp, Canc Prevent Div, Natl Canc Ctr, Bethesda, MD 20892 USA.
[Singer, Eric A.; Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Kaushal, Aradhana] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Turkbey, Baris] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Couvillon, Anna] NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA.
RP Parnes, HL (reprint author), NCI, Res Grp, Canc Prevent Div, Natl Canc Ctr, Bethesda, MD 20892 USA.
EM parnesh@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, MD
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, MD.
NR 68
TC 19
Z9 19
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAY
PY 2012
VL 24
IS 3
BP 243
EP 250
DI 10.1097/CCO.0b013e3283527f99
PG 8
WC Oncology
SC Oncology
GA 931LC
UT WOS:000303220400008
PM 22450149
ER
PT J
AU Singer, EA
Gupta, GN
Srinivasan, R
AF Singer, Eric A.
Gupta, Gopal N.
Srinivasan, Ramaprasad
TI Targeted therapeutic strategies for the management of renal cell
carcinoma
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE chromophobe; clear cell; hereditary leiomyomatosis and renal cell
carcinoma; hereditary papillary renal cancer; mammalian target of
rapamycin; papillary; renal cell carcinoma; targeted therapy; vascular
endothelial growth factor; von Hippel-Lindau
ID HOGG-DUBE-SYNDROME; PHASE-III TRIAL; TUBEROUS SCLEROSIS;
FUMARATE-HYDRATASE; INTERFERON-ALPHA; KIDNEY CANCER; PROGNOSTIC-FACTORS;
GENE FUSION; TRANSLOCATION; MUTATIONS
AB Purpose of review
This article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described.
Recent findings
The treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations.
Summary
Agents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.
C1 [Singer, Eric A.; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gupta, Gopal N.] Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA.
RP Srinivasan, R (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
EM ramasrin@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, MD, USA
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, MD, USA.
NR 59
TC 30
Z9 31
U1 0
U2 3
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 MAY
PY 2012
VL 24
IS 3
BP 284
EP 290
DI 10.1097/CCO.0b013e328351c646
PG 7
WC Oncology
SC Oncology
GA 931LC
UT WOS:000303220400014
PM 22343386
ER
PT J
AU Helfinstein, SM
Fox, NA
Pine, DS
AF Helfinstein, Sarah M.
Fox, Nathan A.
Pine, Daniel S.
TI Approach-Withdrawal and the Role of the Striatum in the Temperament of
Behavioral Inhibition
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE temperament; striatum; approach-withdrawal; anxiety; reinforcement
learning
ID MULTIPLE MEMORY-SYSTEMS; TEMPORAL DIFFERENCE MODELS; CAUDATE-NUCLEUS
LESIONS; DOPAMINE NEURONS; DECISION-MAKING; POSTNATAL-DEVELOPMENT;
REWARD PREDICTION; DORSAL STRIATUM; AMYGDALA MODULATION; SOCIAL
WITHDRAWAL
AB Behavioral inhibition is a temperament characterized in infancy and early childhood by a tendency to withdraw from novel or unfamiliar stimuli. Children exhibiting this disposition, relative to children with other dispositions, are more socially reticent, less likely to initiate interaction with peers, and more likely to develop anxiety over time. Until recently, a dominant model attributed this disposition to reductions in the threshold for engaging the circuitry supporting fear learning, particularly the amygdala. Recent work, however, also has implicated striatal circuitry and other regions that constitute components of a presumed reward system. A series of studies found that behaviorally inhibited adolescents display heightened activation of striatal structures to cues indicating an opportunity to receive reward. This article reviews evidence implicating dual roles for fear and reward circuitry in the expression of behavioral inhibition.
C1 [Fox, Nathan A.] Univ Maryland, Dept Human Dev, Inst Child Study, College Pk, MD 20742 USA.
[Pine, Daniel S.] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA.
RP Fox, NA (reprint author), Univ Maryland, Dept Human Dev, Inst Child Study, 3304 Benjamin Bldg 143, College Pk, MD 20742 USA.
EM fox@umd.edu
NR 114
TC 17
Z9 17
U1 4
U2 24
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 2012
VL 48
IS 3
BP 815
EP 826
DI 10.1037/a0026402
PG 12
WC Psychology, Developmental
SC Psychology
GA 932JK
UT WOS:000303287200021
PM 22148946
ER
PT J
AU Scott, RA
Chu, AY
Grarup, N
Manning, AK
Hivert, MF
Shungin, D
Tonjes, A
Yesupriya, A
Barnes, D
Bouatia-Naji, N
Glazer, NL
Jackson, AU
Kutalik, Z
Lagou, V
Marek, D
Rasmussen-Torvik, LJ
Stringham, HM
Tanaka, T
Aadahl, M
Arking, DE
Bergmann, S
Boerwinkle, E
Bonnycastle, LL
Bornstein, SR
Brunner, E
Bumpstead, SJ
Brage, S
Carlson, OD
Chen, H
Chen, YDI
Chines, PS
Collins, FS
Couper, DJ
Dennison, EM
Dowling, NF
Egan, JS
Ekelund, U
Erdos, MR
Forouhi, NG
Fox, CS
Goodarzi, MO
Grassler, J
Gustafsson, S
Hallmans, G
Hansen, T
Hingorani, A
Holloway, JW
Hu, FB
Isomaa, B
Jameson, KA
Johansson, I
Jonsson, A
Jorgensen, T
Kivimaki, M
Kovacs, P
Kumari, M
Kuusisto, J
Laakso, M
Lecoeur, C
Levy-Marchal, C
Li, G
Loos, RJF
Lyssenko, V
Marmot, M
Marques-Vidal, P
Morken, MA
Muller, G
North, KE
Pankow, JS
Payne, F
Prokopenko, I
Psaty, BM
Renstrom, F
Rice, K
Rotter, JI
Rybin, D
Sandholt, CH
Sayer, AA
Shrader, P
Schwarz, PEH
Siscovick, DS
Stancakova, A
Stumvoll, M
Teslovich, TM
Waeber, G
Williams, GH
Witte, DR
Wood, AR
Xie, WJ
Boehnke, M
Cooper, C
Ferrucci, L
Froguel, P
Groop, L
Kao, WHL
Vollenweider, P
Walker, M
Watanabe, RM
Pedersen, O
Meigs, JB
Ingelsson, E
Barroso, I
Florez, JC
Franks, PW
Dupuis, J
Wareham, NJ
Langenberg, C
AF Scott, Robert A.
Chu, Audrey Y.
Grarup, Niels
Manning, Alisa K.
Hivert, Marie-France
Shungin, Dmitry
Toenjes, Anke
Yesupriya, Ajay
Barnes, Daniel
Bouatia-Naji, Nabila
Glazer, Nicole L.
Jackson, Anne U.
Kutalik, Zoltan
Lagou, Vasiliki
Marek, Diana
Rasmussen-Torvik, Laura J.
Stringham, Heather M.
Tanaka, Toshiko
Aadahl, Mette
Arking, Dan E.
Bergmann, Sven
Boerwinkle, Eric
Bonnycastle, Lori L.
Bornstein, Stefan R.
Brunner, Eric
Bumpstead, Suzannah J.
Brage, Soren
Carlson, Olga D.
Chen, Han
Chen, Yii-Der Ida
Chines, Peter S.
Collins, Francis S.
Couper, David J.
Dennison, Elaine M.
Dowling, Nicole F.
Egan, Josephine S.
Ekelund, Ulf
Erdos, Michael R.
Forouhi, Nita G.
Fox, Caroline S.
Goodarzi, Mark O.
Graessler, Juergen
Gustafsson, Stefan
Hallmans, Goeran
Hansen, Torben
Hingorani, Aroon
Holloway, John W.
Hu, Frank B.
Isomaa, Bo
Jameson, Karen A.
Johansson, Ingegerd
Jonsson, Anna
Jorgensen, Torben
Kivimaki, Mika
Kovacs, Peter
Kumari, Meena
Kuusisto, Johanna
Laakso, Markku
Lecoeur, Cecile
Levy-Marchal, Claire
Li, Guo
Loos, Ruth J. F.
Lyssenko, Valeri
Marmot, Michael
Marques-Vidal, Pedro
Morken, Mario A.
Mueller, Gabriele
North, Kari E.
Pankow, James S.
Payne, Felicity
Prokopenko, Inga
Psaty, Bruce M.
Renstrom, Frida
Rice, Ken
Rotter, Jerome I.
Rybin, Denis
Sandholt, Camilla H.
Sayer, Avan A.
Shrader, Peter
Schwarz, Peter E. H.
Siscovick, David S.
Stancakova, Alena
Stumvoll, Michael
Teslovich, Tanya M.
Waeber, Gerard
Williams, Gordon H.
Witte, Daniel R.
Wood, Andrew R.
Xie, Weijia
Boehnke, Michael
Cooper, Cyrus
Ferrucci, Luigi
Froguel, Philippe
Groop, Leif
Kao, W. H. Linda
Vollenweider, Peter
Walker, Mark
Watanabe, Richard M.
Pedersen, Oluf
Meigs, James B.
Ingelsson, Erik
Barroso, Ines
Florez, Jose C.
Franks, Paul W.
Dupuis, Josee
Wareham, Nicholas J.
Langenberg, Claudia
TI No Interactions Between Previously Associated 2-Hour Glucose Gene
Variants and Physical Activity or BMI on 2-Hour Glucose Levels
SO DIABETES
LA English
DT Article
ID DIABETES PREVENTION PROGRAM; LIFE-STYLE INTERVENTION; COMMON VARIANTS;
TYPE-2; RISK; MELLITUS; ENVIRONMENT; TRAITS; POLYMORPHISMS; PROGRESSION
AB Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP x physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (beta = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 X 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12 mmol/allele, P <= 1.53 X 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P >= 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions. Diabetes 61:1291-1296, 2012
C1 [Scott, Robert A.; Barnes, Daniel; Brage, Soren; Ekelund, Ulf; Forouhi, Nita G.; Loos, Ruth J. F.; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Chu, Audrey Y.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chu, Audrey Y.; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Grarup, Niels; Hansen, Torben; Sandholt, Camilla H.; Pedersen, Oluf] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Fac Hlth Sci, Copenhagen, Denmark.
[Manning, Alisa K.; Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Grarup, Niels; Hansen, Torben; Sandholt, Camilla H.; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Shungin, Dmitry; Renstrom, Frida; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.
[Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden.
[Shungin, Dmitry; Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden.
[Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Integriertes Forsch & Behandlungszentrum IFB Adip, Leipzig, Germany.
[Yesupriya, Ajay; Dowling, Nicole F.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Bouatia-Naji, Nabila; Lecoeur, Cecile; Froguel, Philippe] Inst Pasteur, CNRS, UMR 8199, F-59019 Lille, France.
[Bouatia-Naji, Nabila; Lecoeur, Cecile; Levy-Marchal, Claire; Froguel, Philippe] Univ Lille Nord France, Lille, France.
[Glazer, Nicole L.] Boston Univ, Dept Med Prevent Med & Epidemiol, Boston, MA 02215 USA.
[Jackson, Anne U.; Stringham, Heather M.; Teslovich, Tanya M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Kutalik, Zoltan; Marek, Diana; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Marek, Diana; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Aadahl, Mette; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Arking, Dan E.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA.
[Arking, Dan E.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.; Erdos, Michael R.; Morken, Mario A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Bornstein, Stefan R.; Graessler, Juergen; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.
[Brunner, Eric; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Marmot, Michael] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Bumpstead, Suzannah J.] Wellcome Trust Sanger Inst, Cambridge, England.
[Carlson, Olga D.; Egan, Josephine S.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA.
[Chen, Yii-Der Ida; Goodarzi, Mark O.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Dennison, Elaine M.; Jameson, Karen A.; Sayer, Avan A.; Cooper, Cyrus] Univ Southampton, MRC, Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Fox, Caroline S.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark.
[Hu, Frank B.; Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Jonsson, Anna; Lyssenko, Valeri; Groop, Leif] Lund Univ, Diabet & Endocrinol Unit, Dept Clin Sci, Malmo, Sweden.
[Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Univ Eastern Finland, Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Levy-Marchal, Claire] Hop Robert Debre, INSERM, CIC EC 05, F-75019 Paris, France.
[Li, Guo] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Li, Guo] Univ Washington, Dept Med, Seattle, WA USA.
[Marques-Vidal, Pedro] CHU Vaudois, Inst Social & Prevent Med IUMSP, CH-1011 Lausanne, Switzerland.
[Mueller, Gabriele] Univ Dresden, Inst Med Informat & Biometry, Med Fac Carl Gustav Carus, Dresden, Germany.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Shrader, Peter; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Waeber, Gerard; Vollenweider, Peter] CHUV, Dept Internal Med, Lausanne, Switzerland.
[Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Wood, Andrew R.; Xie, Weijia] Peninsula Coll Med & Dent, Exeter, Devon, England.
[Cooper, Cyrus] Univ Oxford, Botnar Res Ctr, Oxford, England.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England.
[Barroso, Ines] Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Cambridge, England.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
RP Scott, RA (reprint author), Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
EM robert.scott@mrc-epid.cam.ac.uk
RI Marques-Vidal, Pedro/C-9449-2009; Li, Guo/E-5613-2012; Schwarz,
Peter/B-5127-2013; Holloway, John/B-5424-2009; Rice,
Kenneth/A-4150-2013; Brage, Soren/C-6415-2013; Colaus,
PsyColaus/K-6607-2013; Lagou, Vasiliki/N-8451-2013; Witte,
Daniel/C-1722-2008; Prokopenko, Inga/H-3241-2014; Grarup,
Niels/K-2807-2015; BOUATIA-NAJI, NABILA/D-5863-2013
OI Forouhi, Nita/0000-0002-5041-248X; Chen, Han/0000-0002-9510-4923;
Jorgensen, Torben/0000-0001-9453-2830; Marmot,
Michael/0000-0002-2431-6419; Payne, Felicity/0000-0003-4228-581X;
Pankow, James/0000-0001-7076-483X; Bergmann, Sven/0000-0002-6785-9034;
Rybin, Denis/0000-0002-3657-4829; Barnes, Daniel/0000-0002-3781-7570;
Marques-Vidal, Pedro/0000-0002-4548-8500; Kivimaki,
Mika/0000-0002-4699-5627; Aihie Sayer, Avan/0000-0003-1283-6457; Dupuis,
Josee/0000-0003-2871-3603; Kumari, Meena/0000-0001-9716-1035; Schwarz,
Peter/0000-0001-6317-7880; Shungin, Dmitry/0000-0001-7900-5856;
Holloway, John/0000-0001-9998-0464; Rice, Kenneth/0000-0001-5779-4495;
Bouatia-Naji, Nabila/0000-0001-5424-2134; Brage,
Soren/0000-0002-1265-7355; Witte, Daniel/0000-0002-0769-2922;
Prokopenko, Inga/0000-0003-1624-7457; Grarup, Niels/0000-0001-5526-1070;
FU British Heart Foundation [RG/07/008/23674]; Medical Research Council
[G0100222, G0701863, G0902037, G1002084, G19/35, G8802774,
MC_U106179471, MC_U106179473, MC_UP_A100_1003, MC_UP_A620_1014,
MC_UP_A620_1015]; NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [UL1
RR024148, UL1 RR025741]; NHLBI NIH HHS [T32 HL007575]; NIDDK NIH HHS
[K24 DK080140, P30 DK020572, P30 DK063491, R01 DK072041]
NR 28
TC 5
Z9 5
U1 0
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAY
PY 2012
VL 61
IS 5
BP 1291
EP 1296
DI 10.2337/db11-0973
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 930XW
UT WOS:000303179100042
PM 22415877
ER
PT J
AU Brown, RJ
Walter, M
Rother, KI
AF Brown, Rebecca J.
Walter, Mary
Rother, Kristina I.
TI Effects of Diet Soda on Gut Hormones in Youths With Diabetes
SO DIABETES CARE
LA English
DT Article
ID GLUCAGON-LIKE PEPTIDE-1; SWEET TASTE RECEPTORS; HEALTHY-SUBJECTS;
ARTIFICIAL SWEETENER; GLUCOSE-ABSORPTION; BODY-WEIGHT; FOOD-INTAKE;
HUMANS; EXPRESSION; SECRETION
AB OBJECTIVE-In patients with type 2 diabetes, but not type 1 diabetes, abnormal secretion of incretins in response to oral nutrients has been described. In healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study, we examined the effect of diet soda on gut hormones in youths with diabetes.
RESEARCH DESIGN AND METHODS-Subjects aged 12-25 years with type 1 diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (11 = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water, followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C-peptide, GLP-1., glucose-dependent insulinotropic peptide (GIP), and peptide Tyr-Tyr (PYY) were measured for 180 mm. Glucose and GLP-1 have previously been reported for the healthy control subjects.
RESULTS-GLP-1 area under the curve (AUC) was 43% higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes (P = 0.020), similar to control subjects (34% higher, P = 0.029), but was unaffected by diet soda in patients with type 2 diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically different between the two conditions in any group.
CONCLUSIONS-Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not affected by diet soda. The clinical significance of this increased GLP-1 secretion, and its absence in youths with type 2 diabetes, needs to be determined.
C1 [Brown, Rebecca J.; Walter, Mary; Rother, Kristina I.] NIDDK, Bethesda, MD USA.
RP Brown, RJ (reprint author), NIDDK, Bethesda, MD USA.
EM brownrebecca@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 28
TC 27
Z9 27
U1 5
U2 36
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 MAY
PY 2012
VL 35
IS 5
BP 959
EP 964
DI 10.2337/dc11-2424
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 931KN
UT WOS:000303218900006
PM 22410815
ER
PT J
AU Mychaleckyj, JC
Craven, T
Nayak, U
Buse, J
Crouse, JR
Elam, M
Kirchner, K
Lorber, D
Marcovina, S
Sivitz, W
Sperl-Hillen, J
Bonds, DE
Ginsberg, HN
AF Mychaleckyj, Josyf C.
Craven, Timothy
Nayak, Uma
Buse, John
Crouse, John R.
Elam, Marshall
Kirchner, Kent
Lorber, Daniel
Marcovina, Santica
Sivitz, William
Sperl-Hillen, JoAnn
Bonds, Denise E.
Ginsberg, Henry N.
TI Reversibility of Fenofibrate Therapy-Induced Renal Function Impairment
in ACCORD Type 2 Diabetic Participants
SO DIABETES CARE
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; INCREASES CREATININEMIA; PLASMA
HOMOCYSTEINE; SERUM CREATININE; MELLITUS; GEMFIBROZIL; COMBINATION;
PROGRESSION; EQUATION; PEOPLE
AB OBJECTIVE-To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy.
RESEARCH DESIGN AND METHODS-An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate post-trial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, >= 20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, <= 2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy.
RESULTS-At trial end, case subjects had the highest adjusted serum creatinine (+/- SE) mg/dL (1.11 +/- 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (+/- SE) ml/min/1.73 m(2) (68.4 +/- 1.0) versus control subjects (1.01 +/- 0.02; 74.8 +/- 1.3) and placebo subjects (0.98 +/- 0.01; 77.8 +/- 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 +/- 0.02) and eGFR still lower (77.8 +/- 1.0) than control subjects (0.90 +/- 0.02; 81.8 +/- 1.3) but not different from placebo subjects (0.99 +/- 0.01; 76.6 +/- 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes.
CONCLUSIONS-Participants with significant initial on-trial increases in serum creatinine (>= 20%) returned to the same level of renal function as participants receiving placebo while participants who had <= 2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.
C1 [Mychaleckyj, Josyf C.; Nayak, Uma] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Craven, Timothy] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Buse, John] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Crouse, John R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA.
[Elam, Marshall] Memphis VA Med Ctr, Memphis, TN USA.
[Kirchner, Kent] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA.
[Lorber, Daniel] New York Hosp, Lang Ctr Res & Educ, Div Endocrinol, Flushing, NY USA.
[Marcovina, Santica] Univ Washington, NW Lipid Metab & Diabet Res Labs, Seattle, WA 98195 USA.
[Sivitz, William] Univ Iowa Diabet Clin Res, Iowa City, IA USA.
[Sperl-Hillen, JoAnn] Hlth Partners Res Fdn, Minneapolis, MN USA.
[Bonds, Denise E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Ginsberg, Henry N.] Columbia Univ, Dept Med, New York, NY USA.
RP Mychaleckyj, JC (reprint author), Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
EM jcm6t@virginia.edu
FU Abbott Laboratories; 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
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute on Aging; National Eye Institute; Centers for Disease Control
and Prevention; General Clinical Research Centers; Novo Nordisk; Merck;
Eli Lilly; GSK; Johnson Johnson; MannKind
FX This investigator-initiated study was supported by a research grant from
Abbott Laboratories (J.C.M. and T.C.). The ACCORD Trial was supported by
grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181,
N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and
IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by
the National Institute of Diabetes and Digestive and Kidney Diseases;
the National Institute on Aging; the National Eye Institute; the Centers
for Disease Control and Prevention; and by the General Clinical Research
Centers. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca
Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare,
GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis
Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis U.S.,
and Takeda Pharmaceuticals provided study medications, equipment, or
supplies.; J.B. is an investigator (I), consultant (C) or both (I/C)
without any direct financial benefit to him under contracts between his
employer and the following companies: Amylin Pharmaceutical, Inc. (I/C);
Andromeda (I); AstraZeneca (C); Bayhill Therapeutics (C); Biodel (C);
Boehringer Ingelheim (I/C); Bristol-Myers Squibb (I/C); Catabasis (C);
Diartis (C); Elcelyx (C); Eli Lilly and Co. (I/C); Exsulin (C); GI
Dynamics (C); Halozyme, Inc. (I); Hoffman-LaRoche Inc. (I/C); Johnson &
Johnson (I); Lexicon (I); LipoScience (C); Medtronic Mini-Med, Inc. (I);
Merck (C); Metabolon (C); Novan (C); Novo Nordisk Pharmaceuticals, Inc.
(I/C); Osiris Therapeutics, Inc. (C); Orexigen (C); Pfizer, Inc. (I);
Sanofi (I); Tolerex (I); Transition Therapeutics (I); and TransPharma
(C). M.E. is a speaker and consultant for Abbott, Merck, and Schering
Plough. D.L. has received honoraria, consulting fees, and research
support from Novo Nordisk; consulting fees and research support from
Merck; research support from Eli Lilly, GSK, Johnson & Johnson, and
MannKind; owns stock in Merck and Biodel; and is a member of the board
of directors of Biodel. H.N.G. consults for Merck and Abbott, is a
speaker for Merck, and has research grant funding from Merck.
NR 19
TC 36
Z9 36
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAY
PY 2012
VL 35
IS 5
BP 1008
EP 1014
DI 10.2337/dc11-1811
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 931KN
UT WOS:000303218900014
PM 22432114
ER
PT J
AU Stefanovski, D
Youn, JH
Rees, M
Watanabe, RM
Ader, M
Ionut, V
Jackson, AU
Boehnke, M
Collins, FS
Bergman, RN
AF Stefanovski, Dark
Youn, Jang H.
Rees, Matthew
Watanabe, Richard M.
Ader, Marilyn
Ionut, Viorica
Jackson, Anne U.
Boehnke, Michael
Collins, Francis S.
Bergman, Richard N.
TI Estimating Hepatic Glucokinase Activity Using a Simple Model of Lactate
Kinetics
SO DIABETES CARE
LA English
DT Article
ID INSULIN SENSITIVITY; INTRAVENOUS GLUCOSE; GLYCOGEN-SYNTHESIS;
DIABETES-MELLITUS; LIVER-GLYCOGEN; METABOLISM; RESISTANCE; ASSOCIATION;
POPULATION; GLYCOLYSIS
AB OBJECTIVE-Glucokinase (GCK) acts as a component of the "glucose sensor" in pancreatic beta-cells and possibly in other tissues, including the brain. However, >99% of GCK in the body is located in the liver, where it serves as a "gatekeeper", determining the rate of hepatic glucose phosphorylation. Mutations in GCK are a cause of maturity-onset diabetes of the young (MODY), and GCKR, the regulator of GCK in the liver, is a diabetes susceptibility locus. In addition, several GCK activators are being studied as potential regulators of blood glucose. The ability to estimate liver GCK activity in vivo for genetic and pharmacologic studies may provide important physiologic insights into the regulation of hepatic glucose metabolism.
RESEARCH DESIGN AND METHODS-Here we introduce a simple, linear, two-compartment kinetic model that exploits lactate and glucose kinetics observed during the frequently sampled intravenous glucose tolerance test (FSIGT) to estimate liver GCK activity (K-GK), glycolysis (K-12), and whole body fractional lactate clearance (K-01).
RESULTS-To test our working model of lactate, we used cross-sectional FSIGT data on 142 nondiabetic individuals chosen at random from the Finland United States Investigation of NIDDM Genetics study cohort. Parameters KGK, K12, and K01 were precisely estimated. Median model parameter estimates were consistent with previously published values.
CONCLUSIONS-This novel model of lactate kinetics extends the utility of the FSIGT protocol beyond whole-body glucose homeostasis by providing estimates for indices pertaining to hepatic glucose metabolism, including hepatic GCK activity and glycolysis rate.
C1 [Stefanovski, Dark; Youn, Jang H.; Watanabe, Richard M.; Ader, Marilyn; Ionut, Viorica; Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
[Rees, Matthew; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Bergman, RN (reprint author), Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
EM richard.bergman@csmc.edu
FU National Institutes of Health [DK027619, DK029867, DK062370]
FX This work was supported by research grants from the National Institutes
of Health (DK027619, DK029867, and DK062370).
NR 37
TC 10
Z9 10
U1 0
U2 7
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 MAY
PY 2012
VL 35
IS 5
BP 1015
EP 1020
DI 10.2337/dc11-1540
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 931KN
UT WOS:000303218900015
PM 22456868
ER
PT J
AU Chen, LW
Hu, FB
Yeung, E
Tobias, DK
Willett, WC
Zhang, CL
AF Chen, Liwei
Hu, Frank B.
Yeung, Edwina
Tobias, Deirdre K.
Willett, Walter C.
Zhang, Cuilin
TI Prepregnancy Consumption of Fruits and Fruit Juices and the Risk of
Gestational Diabetes Mellitus A prospective cohort study
SO DIABETES CARE
LA English
DT Article
ID WOMEN; METAANALYSIS; VEGETABLES
AB OBJECTIVE-Examine the association of prepregnancy habitual consumption of fruits and fruit juices and gestational diabetes mellitus (GDM) risk.
RESEARCH DESIGN AND METHODS-A prospective study among women with at least one singleton pregnancy in the Nurses' Health Study II from 1991 to 2001.
RESULTS-Among 13,475 women, 860 reported a first diagnosis of GDM. The adjusted relative risks (RRs) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (95% Cl 0.65-0.98), 0.90 (0.73-1.10), 0.80 (0.64-1.00), and 0.93 (0.76-1.16), respectively. The corresponding RRs for fruit juice were 1.00, 0.82 (0.66-1.01), 0.78 (0.63-0.96), 0.84 (0.68-1.04), and 1.00 (0.81-1.23).
CONCLUSIONS-These data suggest that prepregnancy higher consumption of whole fruits is not associated with an increased GDM risk. The association between fruit juices and GDM risk appears to be nonlinear.
C1 [Yeung, Edwina; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Chen, Liwei] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, New Orleans, LA USA.
[Hu, Frank B.; Tobias, Deirdre K.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hu, Frank B.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hu, Frank B.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
EM zhangcu@mail.nih.gov
RI Yeung, Edwina/F-5992-2015
OI Yeung, Edwina/0000-0002-3851-2613
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health [CA-50385, DK-58845]; School
of Public Health, Louisiana State University Health Science Center
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, the National Institutes of Health (to L.C., E.Y., and
C.Z.), and the School of Public Health, Louisiana State University
Health Science Center. The Nurses' Health Study II was funded by
research grants CA-50385 and DK-58845 from the National Institutes of
Health.
NR 12
TC 6
Z9 6
U1 0
U2 5
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 MAY
PY 2012
VL 35
IS 5
BP 1079
EP 1082
DI 10.2337/dc11-2105
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 931KN
UT WOS:000303218900026
PM 22446174
ER
PT J
AU Dunn, JP
Kessler, RM
Feurer, ID
Volkow, ND
Patterson, BW
Ansari, MS
Li, R
Marks-Shulman, P
Abumrad, NN
AF Dunn, Julia P.
Kessler, Robert M.
Feurer, Irene D.
Volkow, Nora D.
Patterson, Bruce W.
Ansari, Mohammad S.
Li, Rui
Marks-Shulman, Pamela
Abumrad, Naji N.
TI Relationship of Dopamine Type 2 Receptor Binding Potential With Fasting
Neuroendocrine Hormones and Insulin Sensitivity in Human Obesity
SO DIABETES CARE
LA English
DT Article
ID NUCLEUS-ACCUMBENS; BRAIN ACTIVITY; FOOD-INTAKE; IN-VIVO; GHRELIN;
LEPTIN; REWARD; INCREASES; RESPONSES; STRIATUM
AB OBJECTIVE-Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity.
RESEARCH DESIGN AND METHODS-We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S-I) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [F-18] fallypride (radic ligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S-I was determined by modified oral glucose tolerance test.
RESULTS-Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S-I was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BM I, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand.
CONCLUSIONS-Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.
C1 [Dunn, Julia P.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Kessler, Robert M.; Ansari, Mohammad S.; Li, Rui] Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37212 USA.
[Feurer, Irene D.; Marks-Shulman, Pamela; Abumrad, Naji N.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA.
[Feurer, Irene D.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Patterson, Bruce W.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
RP Dunn, JP (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
EM julia.dunn@va.gov
FU National Institutes of Health from National Center for Research
Resources [UL1-RR-024975]; National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) [DK-20593]; NIDDK (Vanderbilt Digestive
Disease Research Center) [DK-058404]; Washington University Nutrition
and Obesity Research Center [P30-DK-56341]; National Institute of
Environmental Health Sciences [K12-ES-015855]; NIDDK [DK-70860]
FX This study was supported by National Institutes of Health Grants
UL1-RR-024975 from the National Center for Research Resources
(Vanderbilt Clinical and Translational Science Award), DK-20593 from the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK;
Vanderbilt Diabetes Research and Training Award), DK-058404 from the
NIDDK (Vanderbilt Digestive Disease Research Center), P30-DK-56341 from
the Washington University Nutrition and Obesity Research Center,
K12-ES-015855 from the National Institute of Environmental Health
Sciences (Vanderbilt Environmental Health Science Scholars Program) to
J.P.D., and DK-70860 from the NIDDK to N.N.A.
NR 40
TC 49
Z9 50
U1 2
U2 8
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 MAY
PY 2012
VL 35
IS 5
BP 1105
EP 1111
DI 10.2337/dc11-2250
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 931KN
UT WOS:000303218900031
PM 22432117
ER
PT J
AU Soerensen, M
Dato, S
Tan, QH
Thinggaard, M
Kleindorp, R
Beekman, M
Jacobsen, R
Suchiman, HED
de Craen, AJM
Westendorp, RGJ
Schreiber, S
Stevnsner, T
Bohr, VA
Slagboom, PE
Nebel, A
Vaupel, JW
Christensen, K
McGue, M
Christiansen, L
AF Soerensen, Mette
Dato, Serena
Tan, Qihua
Thinggaard, Mikael
Kleindorp, Rabea
Beekman, Marian
Jacobsen, Rune
Suchiman, H. Eka D.
de Craen, Anton J. M.
Westendorp, Rudi G. J.
Schreiber, Stefan
Stevnsner, Tinna
Bohr, Vilhelm A.
Slagboom, P. Eline
Nebel, Almut
Vaupel, James W.
Christensen, Kaare
McGue, Matt
Christiansen, Lene
TI Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage
signaling and repair and pro/antioxidant pathway genes: Cross sectional
and longitudinal studies
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Human longevity; Association study; Case-control data; Longitudinal
data; Candidate study
ID GENOME-WIDE ASSOCIATION; LIFE-SPAN; GHRELIN GENE; MUTANT MICE; KLOTHO
GENE; SURVIVAL; POLYMORPHISMS; CANCER; FOXO3A; AGE
AB Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways.
In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing.
In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing.
When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also in late life survival. In addition, rs207444 (XDH) presented the same direction of effect when inspecting the 6 SNPs from the longitudinal study in the case-control data, hence, suggesting an effect also in survival from middle age to old age.
No formal replications were observed when investigating the 11 SNPs from the case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans, although rs11571461 (RAD52) did show a supportive nonsignificant tendency (OR=1.162, 95% CI = 0.927-1.457). The same was true for rs10047589 (TNXRD1) (HR=0.758, 95% CI=0.543-1.058) when examining the 6 SNPs from the longitudinal study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563).
In conclusion, the present candidate gene based association study, the largest to date applying a pathway approach, not only points to potential new longevity loci, but also underlines the difficulties of replicating association findings in independent study populations and thus the difficulties in identifying universal longevity polymorphisms. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Jacobsen, Rune; Vaupel, James W.; Christensen, Kaare; McGue, Matt; Christiansen, Lene] Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, DK-5000 Odense C, Denmark.
[Soerensen, Mette; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark.
[Soerensen, Mette; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark.
[Dato, Serena] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, CS, Italy.
[Kleindorp, Rabea; Schreiber, Stefan; Nebel, Almut] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
[Kleindorp, Rabea; Schreiber, Stefan; Nebel, Almut] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany.
[Beekman, Marian; Suchiman, H. Eka D.; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands.
[Beekman, Marian; Suchiman, H. Eka D.; Slagboom, P. Eline] Leiden Univ, Med Ctr, Netherlands Consortium Hlth Aging, NL-2300 RC Leiden, Netherlands.
[de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands.
[Stevnsner, Tinna; Bohr, Vilhelm A.] Aarhus Univ, Dept Mol Biol & Genet, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Vaupel, James W.] Max Planck Inst Demog Res, D-18057 Rostock, Germany.
[McGue, Matt] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
RP Christiansen, L (reprint author), Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark.
EM lchristiansen@health.sdu.dk
RI Christensen, Kaare/C-2360-2009; Nebel, Almut/E-4196-2010;
Lindahl-Jacobsen, Rune/J-2985-2012; Schreiber, Stefan/B-6748-2008;
Soerensen, Mette/O-1817-2015; Slagboom, P. Eline/R-4790-2016; Suchiman,
H. Eka D./F-5024-2017;
OI Christensen, Kaare/0000-0002-5429-5292; Lindahl-Jacobsen,
Rune/0000-0002-4622-9826; Schreiber, Stefan/0000-0003-2254-7771;
Slagboom, P. Eline/0000-0002-2875-4723; Suchiman, H. Eka
D./0000-0002-7168-5516; Soerensen, Mette/0000-0001-5268-3366; Beekman,
Marian/0000-0003-0585-6206; dato, serena/0000-0003-2589-7929
FU Max-Planck Institute for Demographic Research (Rostock, Germany);
INTERREG; European Regional Development Fund; National Institute on
Aging [P01 AG08761]; Netherlands Consortium for Healthy Aging of the
Netherlands Genomics Initiative/Netherlands Organization for Scientific
Research (NWO) [050-060-810]; European Union [259679]; Novo Nordisk
Foundation; Aase and Ejnar Danielsen Foundation; Augustinus Foundation;
Brodrene Hartmann Foundation; King Christian the 10th Foundation; Einer
Willumsens Mindelegat Foundation; VELUX Foundation
FX This study was supported by the Max-Planck Institute for Demographic
Research (Rostock, Germany), the INTERREG 4 A programme
Syddanmark-Schleswig-K.E.R.N (by EU funds from the European Regional
Development Fund), the National Institute on Aging (P01 AG08761), a
Dutch grant from the Netherlands Consortium for Healthy Aging (Grant
050-060-810) in the framework of the Netherlands Genomics
Initiative/Netherlands Organization for Scientific Research (NWO), the
European Union's Seventh Framework Programme (FP7/2007-2011) under grant
agreement no 259679, the Novo Nordisk Foundation, the Aase and Ejnar
Danielsen Foundation, the Augustinus Foundation, the Brodrene Hartmann
Foundation, the King Christian the 10th Foundation and the Einer
Willumsens Mindelegat Foundation. The Danish Aging Research Center is
supported by a grant from the VELUX Foundation. Susanne Knudsen, Steen
Gregersen, Ulla Munk, Shuxia Li, Anne Mette Hedegaard Nielsen, Marlene
Graff Sorensen and Lene Elnegaard are thanked for excellent technical
work.
NR 62
TC 31
Z9 31
U1 1
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
J9 EXP GERONTOL
JI Exp. Gerontol.
PD MAY
PY 2012
VL 47
IS 5
BP 379
EP 387
DI 10.1016/j.exger.2012.02.010
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 929ZR
UT WOS:000303105200005
PM 22406557
ER
PT J
AU Liu, J
Zhou, L
Xiong, KM
Godlewski, G
Mukhopadhyay, B
Tam, J
Yin, S
Gao, P
Shan, X
Pickel, J
Bataller, R
O'Hare, J
Scherer, T
Buettner, C
Kunos, G
AF Liu, Jie
Zhou, Liang
Xiong, Keming
Godlewski, Grzegorz
Mukhopadhyay, Bani
Tam, Joseph
Yin, Shi
Gao, Peter
Shan, Xin
Pickel, James
Bataller, Ramon
O'Hare, James
Scherer, Thomas
Buettner, Christoph
Kunos, George
TI Hepatic Cannabinoid Receptor-1 Mediates Diet-Induced Insulin Resistance
via Inhibition of Insulin Signaling and Clearance in Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE NASH; Signal Transduction; Mouse Model; Liver Disease
ID ENDOPLASMIC-RETICULUM STRESS; INDUCED OBESE MICE; RANDOMIZED
CONTROLLED-TRIAL; BOUND TRANSCRIPTION FACTOR; CB1 RECEPTOR; ER STRESS;
CARDIOMETABOLIC RISK; DEGRADING ENZYME; ADIPOSE-TISSUE; GLUCOSE
AB BACKGROUND & AIMS: Obesity-related insulin resistance contributes to cardiovascular disease. Cannabinoid receptor-1 (CB1) blockade improves insulin sensitivity in obese animals and people, suggesting endocannabinoid involvement. We explored the role of hepatic CB1 in insulin resistance and inhibition of insulin signaling pathways. METHODS: Wild-type mice and mice with disruption of CB1 (CB1-/- mice) or with hepatocyte-specific deletion or transgenic overexpression of CB1 were maintained on regular chow or a high-fat diet (HFD) to induce obesity and insulin resistance. Hyperinsulinemic-euglycemic clamp analysis was used to analyze the role of the liver and hepatic CB1 in HFD-induced insulin resistance. The cellular mechanisms of insulin resistance were analyzed in mouse and human isolated hepatocytes using small interfering or short hairpin RNAs and lentiviral knockdown of gene expression. RESULTS: The HFD induced hepatic insulin resistance in wild-type mice, but not in CB1-/-mice or mice with hepatocyte-specific deletion of CB1. CB1-/-mice that overexpressed CB1 specifically in hepatocytes became hyperinsulinemic as a result of reduced insulin clearance due to down-regulation of the insulin-degrading enzyme. However, they had increased hepatic glucose production due to increased glycogenolysis, indicating hepatic insulin resistance; this was further increased by the HFD. In mice with hepatocytes that express CB1, the HFD or CB1 activation induced the endoplasmic reticulum stress response via activation of the Bip-PERK-eIF2 alpha protein translation pathway. In hepatocytes isolated from human or mouse liver, CB1 activation caused endoplasmic reticulum stress-dependent suppression of insulin-induced phosphorylation of akt-2 via phosphorylation of IRS1 at serine-307 and by inducing the expression of the serine and threonine phosphatase Phlpp1. Expression of CB1 was up-regulated in samples from patients with nonalcoholic fatty liver disease. CONCLUSIONS: Endocannabinoids contribute to diet-induced insulin resistance in mice via hepatic CB1-mediated inhibition of insulin signaling and clearance.
C1 [Liu, Jie; Zhou, Liang; Xiong, Keming; Godlewski, Grzegorz; Mukhopadhyay, Bani; Tam, Joseph; Yin, Shi; Gao, Peter; Shan, Xin; Kunos, George] NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA.
[Pickel, James] NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA.
[Bataller, Ramon] Inst Invest Biomed August Pi & Sunyer, Liver Unit, Barcelona, Spain.
[O'Hare, James; Scherer, Thomas; Buettner, Christoph] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Liu, J (reprint author), NIAAA, Lab Physiol Studies, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA.
EM jiel@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism
FX Supported by intramural funds from the National Institute on Alcohol
Abuse and Alcoholism.
NR 56
TC 56
Z9 56
U1 3
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAY
PY 2012
VL 142
IS 5
BP 1218
EP +
DI 10.1053/j.gastro.2012.01.032
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 930CK
UT WOS:000303113600040
PM 22307032
ER
PT J
AU Kim, SM
Leem, SH
Chu, IS
Park, YY
Kim, SC
Kim, SB
Park, ES
Lim, JY
Heo, J
Kim, YJ
Kim, DG
Kaseb, A
Park, YN
Wang, XW
Thorgeirsson, SS
Lee, JS
AF Kim, Soo Mi
Leem, Sun-Hee
Chu, In-Sun
Park, Yun-Yong
Kim, Sang Cheol
Kim, Sang-Bae
Park, Eun Sung
Lim, Jae Yun
Heo, Jeonghoon
Kim, Yoon Jun
Kim, Dae-Ghon
Kaseb, Ahmed
Park, Young Nyun
Wang, Xin Wei
Thorgeirsson, Snorri S.
Lee, Ju-Seog
TI Sixty-five gene-based risk score classifier predicts overall survival in
hepatocellular carcinoma
SO HEPATOLOGY
LA English
DT Article
ID HEPATITIS-B-VIRUS; THERAPEUTIC TARGETS; STAGING-SYSTEM; RECURRENCE;
EXPRESSION; CANCER; PROGNOSIS; LIMITATIONS; SIGNATURE; PATTERNS
AB Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy-to-use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (P = 5.6 x 10(-5), n = 100) and the second test cohort (P = 5.0 x 10(-5), n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = 0.001 for OS). Conclusion: The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets. (HEPATOLOGY 2011)
C1 [Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77054 USA.
[Kim, Soo Mi] Chonbuk Natl Univ, Dept Physiol, Med Sch & Hosp, Jeonju, South Korea.
[Leem, Sun-Hee] Dong A Univ, Dept Biol Sci, Pusan, South Korea.
[Chu, In-Sun; Kim, Sang Cheol] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Taejon, South Korea.
[Park, Eun Sung] Yonsei Univ, Coll Med, Inst Med Convergence, Seoul, South Korea.
[Lim, Jae Yun] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
[Heo, Jeonghoon] Kosin Univ, Coll Med, Pusan, South Korea.
[Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea.
[Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea.
[Kim, Dae-Ghon] Chonbuk Natl Univ, Dept Internal Med, Div Gastroenterol & Hepatol, Med Sch & Hosp, Jeonju, South Korea.
[Kaseb, Ahmed] Univ Texas MD Anderson Canc Ctr, Dept GI Med Oncol, Div Canc Med, Houston, TX 77030 USA.
[Park, Young Nyun] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea.
[Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Lee, JS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Unit 950,1515 Holcombe Blvd, Houston, TX 77054 USA.
EM jlee@mdanderson.org
RI Kim, Yoon Jun/J-2746-2012; Wang, Xin/B-6162-2009
FU University of Texas MD Anderson Cancer Center; NCI CCSG [CA106672]
FX Funded by the intramural faculty fund of the University of Texas MD
Anderson Cancer Center to J-S Lee; MD Anderson Cancer Center is
partially funded by NCI CCSG Core Grant CA106672. Microarray data:
GSE1898, GSE4024, GSE9843, GSE14520, GSE16757, and E-TABM-36.
NR 36
TC 27
Z9 27
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2012
VL 55
IS 5
BP 1443
EP 1452
DI 10.1002/hep.24813
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 929GN
UT WOS:000303049400015
PM 22105560
ER
PT J
AU Voltaggio, L
Murray, R
Lasota, J
Miettinen, M
AF Voltaggio, Lysandra
Murray, Rebecca
Lasota, Jerzy
Miettinen, Markku
TI Gastric schwannoma: a clinicopathologic study of 51 cases and critical
review of the literature
SO HUMAN PATHOLOGY
LA English
DT Review
DE Schwannoma; Stomach; Nerve sheath tumor; S100 protein; GFAP; Prognosis;
Chromosome 22; Polyploidy
ID GASTROINTESTINAL STROMAL TUMORS; NERVE SHEATH TUMORS; MALIGNANT
SCHWANNOMA; MELANOTIC SCHWANNOMA; BENIGN SCHWANNOMA; PDGFRA MUTATIONS;
DIGESTIVE-TRACT; STOMACH; FEATURES; PATIENT
AB Schwannoma is a rare gastrointestinal mesenchymal tumor, as the vast majority of gastric mesenchymal tumors are gastrointestinal stromal tumors. In this study, we analyzed clinicopathologically 51 gastric schwannomas. These tumors predominantly occurred in older adults with a marked female predominance (40 women and 11 men; median and mean ages, 60 and 58 years). They variably presented with gastric discomfort, bleeding, or rarely gastric outlet obstruction; and many were incidental findings during other medical procedures. The tumors ranged from 1 to 10.5 cm (median, 4.5 cm). The typical histologic features included spindle cells usually with microtrabecular architecture and focal nuclear atypia, and peritumoral lymphoid cuff, whereas features of soft tissue schwannomas, such as encapsulation, nuclear palisading, vascular hyalinization, and dilatation, were absent or infrequent. Median mitotic count was 2/50 high-power fields, with the highest count being 13/50 high-power fields. No malignant variants were recognized, and long-term follow-up did not reveal recurrences or metastases. Immunohistochemically, all examined tumors were S100 protein positive and most were also GFAP positive, whereas CD34 and NF68 were encountered rarely and all tumors were negative for HMB45, KIT, DOG1/Ano 1, smooth muscle actin, desmin, and synaptophysin. None of the 9 tumors studied contained gastrointestinal stromal tumor specific KIT or PDGFRA mutations. Fluorescence in situ hybridization studies revealed multiple signals with BCR probe (chromosome 22) and centromeric probes for chromosomes 2 and 18 suggesting polyploidy. These findings indicate that gastric schwannoma is a distinctive form of peripheral nerve sheath tumor that in many ways differs from soft tissue schwannoma. It should be distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the gastrointestinal tract, such as the S100 protein positive gastrointestinal clear cell sarcoma and metastatic melanoma. Published by Elsevier Inc.
C1 [Lasota, Jerzy; Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Voltaggio, Lysandra; Murray, Rebecca] George Washington Univ Hosp, Dept Pathol, Washington, DC 20037 USA.
[Miettinen, Markku] Armed Forces Inst Pathol, Silver Spring, MD 20306 USA.
RP Miettinen, M (reprint author), NCI, Lab Surg Pathol, Bethesda, MD 20892 USA.
EM Markku.Miettinen@nih.gov
FU National Institutes of Health; National Cancer Institute
FX This research was supported in part by the intramural research program
of the National Institutes of Health and the National Cancer Institute.
NR 42
TC 36
Z9 43
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 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD MAY
PY 2012
VL 43
IS 5
BP 650
EP 659
DI 10.1016/j.humpath.2011.07.006
PG 10
WC Pathology
SC Pathology
GA 932JY
UT WOS:000303288600005
PM 22137423
ER
PT J
AU Davidson, B
Stavnes, HT
Risberg, B
Nesland, JM
Wohlschlaeger, J
Yang, YQ
Shih, IM
Wang, TL
AF Davidson, Ben
Stavnes, Helene Tuft
Risberg, Bjorn
Nesland, Jahn M.
Wohlschlaeger, Jeremias
Yang, Yanqin
Shih, Ie-Ming
Wang, Tian-Li
TI Gene expression signatures differentiate adenocarcinoma of lung and
breast origin in effusions
SO HUMAN PATHOLOGY
LA English
DT Article
DE Gene expression array; Breast adenocarcinoma; Lung adenocarcinoma;
Serous effusions; Differential diagnosis
ID CARBONIC-ANHYDRASE-XII; MATRIX METALLOPROTEINASE-7; PLEURAL EFFUSION;
CANCER PATIENTS; POOR-PROGNOSIS; MESSENGER-RNA; ANTIGEN EVA; CARCINOMA;
NONSMALL; PROTEIN
AB Lung and breast adenocarcinoma at advanced stages commonly involve the serosal cavities, giving rise to malignant effusions. The aim of the present study was to compare the global gene expression patterns of metastases from these 2 malignancies, to expand and improve the diagnostic panel of biomarkers currently available for their differential diagnosis, as well as to define type-specific biological targets. Gene expression profiles of 7 breast and 4 lung adenocarcinoma effusions were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated lung from breast adenocarcinoma samples. We identified 289 unique probes that were significantly differentially expressed in the 2 cancers by greater than 2-fold using moderated t statistics, of which 65 and 224 were overexpressed in breast and lung adenocarcinoma, respectively. Genes overexpressed in breast adenocarcinoma included TFF1, TFF3, FOXA1, CA12, PITX1, RARRES1, CITED4, MYC, TFAP2A, EFHD1, TOB1, SPDEF, FASN, and TH. Genes overexpressed in lung adenocarcinoma included TITF1, SFTPG, MMP7, EVA1, GPR116, HOP, SCGB3A2, and MET. The differential expression of 15 genes was validated by quantitative real-time PCR, and differences in 8 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes breast adenocarcinoma from lung adenocarcinoma and identifies genes that are differentially expressed in these 2 tumor types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Davidson, Ben] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Pathol, Div Pathol, N-0310 Oslo, Norway.
[Davidson, Ben; Nesland, Jahn M.] Univ Oslo, Fac Med, N-0316 Oslo, Norway.
[Wohlschlaeger, Jeremias] Univ Hosp Essen, Dept Pathol & Neuropathol, Essen, Germany.
[Yang, Yanqin] NHLBI, Gene Express Core Facil, NIH, Bethesda, MD 20892 USA.
[Shih, Ie-Ming] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Shih, Ie-Ming; Wang, Tian-Li] Johns Hopkins Med Inst, Dept Gynecol Obstet & Oncol, Baltimore, MD 21205 USA.
RP Davidson, B (reprint author), Norwegian Radium Hosp, Oslo Univ Hosp, Dept Pathol, Div Pathol, N-0310 Oslo, Norway.
EM bend@medisin.uio.no; tlw@welch.jhu.edu
FU Norwegian Cancer Society; Research Foundation at the Norwegian Radium
Hospital; NIH [R01 CA103937]
FX This work was supported by grants from the Norwegian Cancer Society and
the Research Foundation at the Norwegian Radium Hospital as well as NIH
grant R01 CA103937.
NR 57
TC 5
Z9 5
U1 0
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 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD MAY
PY 2012
VL 43
IS 5
BP 684
EP 694
DI 10.1016/j.humpath.2011.06.015
PG 11
WC Pathology
SC Pathology
GA 932JY
UT WOS:000303288600009
PM 21937081
ER
PT J
AU Margalit, M
Yogev, L
Yavetz, H
Lehavi, O
Hauser, R
Botchan, A
Barda, S
Levitin, F
Weiss, M
Pastan, I
Wreschner, DH
Paz, G
Kleiman, SE
AF Margalit, M.
Yogev, L.
Yavetz, H.
Lehavi, O.
Hauser, R.
Botchan, A.
Barda, S.
Levitin, F.
Weiss, M.
Pastan, I.
Wreschner, D. H.
Paz, G.
Kleiman, S. E.
TI Involvement of the prostate and testis expression (PATE)-like proteins
in spermoocyte interaction
SO HUMAN REPRODUCTION
LA English
DT Article
DE human sperm; PATE genes; human spermatogenesis; TFP; Ly-6; uPAR
proteins; oolemma penetration
ID SPERM-EGG FUSION; ACROSOME REACTION; PLASMA-MEMBRANE; HUMAN-SPERMATOZOA;
FERTILIZING ABILITY; PHOSPHOLIPASE A(2); AZOOSPERMIC MEN; IN-VITRO;
PLASMINOGEN-ACTIVATOR; EQUATORIAL SEGMENT
AB The prostate and testis expression (PATE)-like family of proteins are expressed mainly in the male genital tract. They are localized in the sperm head and are homologous to SP-10, the acrosomal vesicle protein also named ACRV1. Our aim was to characterize the expression and functional role of three PATE-like proteins in the testis and ejaculated sperm.
The expression and localization of PATE-like proteins in human testis biopsies (n 95) and sperm cells were assessed by RTPCR, immunohistochemistry and immunofluorescence staining (at least 600 sperm cells per specimen). The function of the PATE protein was tested by the hemizona assay and hamster egg penetration test (HEPT).
PATE and PATE-M genes and proteins were present almost exclusively in germ cells in the testis: immunoflourescence showed that the percentage of germ cells positive for PATE, PATE-M and PATE-B was 85, 50 and 2, respectively. PATE and PATE-M proteins were localized in the equatorial segment of the sperm head, while PATE-B protein was localized in the post-acrosomal region. A polyclonal antibody (Ab, at 1:50 and 1:200 dilutions) against the PATE protein did not inhibit spermzona binding in the hemizona assay (hemizona index of 89.6 10 and 87 36, respectively). However, there was inhibition of spermoolemma fusion and penetration in the HEPT (penetration index: without Ab 7 3.9; Ab dilution of 1:100, 4 3.5; Ab dilution of 1:20, 0.6 1.2, P 0.001).
Our data suggest that PATE protein is involved in spermoolemma fusion and penetration but not spermzona binding.
C1 [Margalit, M.; Yogev, L.; Yavetz, H.; Lehavi, O.; Hauser, R.; Botchan, A.; Barda, S.; Paz, G.; Kleiman, S. E.] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Inst Study Fertil,Lis Matern Hosp, IL-69978 Tel Aviv, Israel.
[Levitin, F.; Wreschner, D. H.] Tel Aviv Univ, Dept Cell Res & Immunol, Ramat Aviv, Israel.
[Weiss, M.] Assaf Harofe Med Ctr, Dept Endocrinol, Zerifin, Israel.
[Pastan, I.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kleiman, SE (reprint author), Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Inst Study Fertil,Lis Matern Hosp, IL-69978 Tel Aviv, Israel.
EM ser@tasmc.health.gov.il
OI Barda, Shimi/0000-0001-6553-0350
FU Alan and Ada Selwyn Chair in Clinical Infertility Research and Molecular
Medicine (Melbourne, Australia); NIH, National Cancer Institute, Center
for Cancer Research
FX The research was carried out under the auspices of the Alan and Ada
Selwyn Chair in Clinical Infertility Research and Molecular Medicine
(Melbourne, Australia) granted to one of the authors (G.P.). This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 50
TC 7
Z9 7
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD MAY
PY 2012
VL 27
IS 5
BP 1238
EP 1248
DI 10.1093/humrep/des064
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 930TB
UT WOS:000303161900002
PM 22402205
ER
PT J
AU Kwon, S
Park, HS
Stanley, CJ
Kim, J
Kim, J
Damiano, DL
AF Kwon, Suncheol
Park, Hyung-Soon
Stanley, Christopher J.
Kim, Jung
Kim, Jonghyun
Damiano, Diane L.
TI A Practical Strategy for sEMG-Based Knee Joint Moment Estimation During
Gait and Its Validation in Individuals With Cerebral Palsy
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Cerebral palsy (CP); estimation of knee internal moment; muscular
cocontraction; sEMG-moment relationship
ID SINGLE-LIMB STANCE; FORCE MODEL; CROUCH GAIT; EMG; MUSCLES; PREVALENCE;
EXTENSION; CHILDREN; HIP; ELECTROMYOGRAPHY
AB Individuals with cerebral palsy have neurological deficits that may interfere with motor function and lead to abnormal walking patterns. It is important to know the joint moment generated by the patient's muscles during walking in order to assist the suboptimal gait patterns. In this paper, we describe a practical strategy for estimating the internal moment of a knee joint from surface electromyography (sEMG) and knee joint angle measurements. This strategy requires only isokinetic knee flexion and extension tests to obtain a relationship between the sEMG and the knee internal moment, and it does not necessitate comprehensive laboratory calibration, which typically requires a 3-D motion capture system and ground reaction force plates. Four estimation models were considered based on different assumptions about the functions of the relevant muscles during the isokinetic tests and the stance phase of walking. The performance of the four models was evaluated by comparing the estimated moments with the gold standard internal moment calculated from inverse dynamics. The results indicate that an optimal estimation model can be chosen based on the degree of cocontraction. The estimation error of the chosen model is acceptable (normalized root-mean-squared error: 0.15-0.29, R: 0.71-0.93) compared to previous studies (Doorenbosch and Harlaar, 2003; Doorenbosch and Harlaar, 2004; Doorenbosch, Joosten, and Harlaar, 2005), and this strategy provides a simple and effective solution for estimating knee joint moment from sEMG.
C1 [Park, Hyung-Soon; Stanley, Christopher J.; Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kwon, Suncheol] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea.
RP Park, HS (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM sun.kwon@kaist.ac.kr; parkhs@cc.nih.gov; stanleycj@cc.nih.gov;
kimj13@cc.nih.gov kimj13@cc.nih.gov; kimj13@cc.nih.gov kimj13@cc.nih.gov
RI Park, Hyung-Soon/B-3334-2010; Kim, Jung/C-1636-2011; Van Mulders,
Benjamin/P-1241-2014; Damiano, Diane/B-3338-2010
OI Park, Hyung-Soon/0000-0003-4274-7420; Damiano, Diane/0000-0002-2770-5356
FU Je Won Research Foundation; National Research Foundation of Korea (NRF);
Ministry of Education, Science and Technology [2011-0020934]; National
Institutes of Health [10-CC-0073]
FX This work was supported by the Je Won Research Foundation, the Happy
Tech. Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology under Grant
2011-0020934, and the Intramural Research Program at the National
Institutes of Health (Protocol #: 10-CC-0073). S. Kwon and H.-S. Park
equally contributed to the work. Asterisk indicates corresponding
author.
NR 43
TC 8
Z9 9
U1 0
U2 18
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD MAY
PY 2012
VL 59
IS 5
BP 1480
EP 1487
DI 10.1109/TBME.2012.2187651
PG 8
WC Engineering, Biomedical
SC Engineering
GA 931FJ
UT WOS:000303201000031
PM 22410952
ER
PT J
AU Yahiro, K
Tsutsuki, H
Ogura, K
Nagasawa, S
Moss, J
Noda, M
AF Yahiro, Kinnosuke
Tsutsuki, Hiroyasu
Ogura, Kohei
Nagasawa, Sayaka
Moss, Joel
Noda, Masatoshi
TI Regulation of Subtilase Cytotoxin-Induced Cell Death by an RNA-Dependent
Protein Kinase-Like Endoplasmic Reticulum Kinase-Dependent Proteasome
Pathway in HeLa Cells
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TOXIGENIC ESCHERICHIA-COLI; STRESS-SIGNALING PATHWAYS; INDUCED
APOPTOSIS; MAMMALIAN-CELLS; TRANSLATION; DEGRADATION; TRANSCRIPTION;
SURVIVAL; FAMILY; IRE1
AB Shiga-toxigenic Escherichia coli (STEC) produces subtilase cytotoxin (SubAB), which cleaves the molecular chaperone BiP in the endoplasmic reticulum (ER), leading to an ER stress response and then activation of apoptotic signaling pathways. Here, we show that an early event in SubAB-induced apoptosis in HeLa cells is mediated by RNA-dependent protein kinase (PKR)-like ER kinase (PERK), not activating transcription factor 6 (ATF6) or inositol-requiring enzyme 1(Ire1), two other ER stress sensors. PERK knockdown suppressed SubAB-induced eIF2 alpha phosphorylation, activating transcription factor 4 (ATF4) expression, caspase activation, and cytotoxicity. Knockdown of eIF2 alpha by small interfering RNA (siRNA) or inhibition of eIF2 alpha dephosphorylation by Sal003 enhanced SubAB-induced caspase activation. Treatment with proteasome inhibitors (i.e., MG132 and lactacystin), but not a general caspase inhibitor (Z-VAD) or a lysosome inhibitor (chloroquine), suppressed SubAB-induced caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage, suggesting that the ubiquitin-proteasome system controls events leading to caspase activation, i.e., Bax/Bak conformational changes, followed by cytochrome c release from mitochondria. Levels of ubiquitinated proteins in HeLa cells were significantly decreased by SubAB treatment. Further, in an early event, some antiapoptotic proteins, which normally turn over rapidly, have their synthesis inhibited, and show enhanced degradation via the proteasome, resulting in apoptosis. In PERK knockdown cells, SubAB-induced loss of ubiquitinated proteins was inhibited. Thus, SubAB-induced ER stress is caused by BiP cleavage, leading to PERK activation, not by accumulation of ubiquitinated proteins, which undergo PERK-dependent degradation via the ubiquitin-proteasome system.
C1 [Yahiro, Kinnosuke; Tsutsuki, Hiroyasu; Ogura, Kohei; Nagasawa, Sayaka; Noda, Masatoshi] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba, Japan.
[Nagasawa, Sayaka] Chiba Univ, Grad Sch Med, Dept Legal Med, Chiba, Japan.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba, Japan.
EM yahirok@faculty.chiba-u.jp
FU Ministry of Education, Science and Culture of Japan; Japan Science and
Technology Agency; National Institutes of Health, National Heart, Lung,
and Blood Institute
FX This work was supported by grants in aid for Scientific Research from
the Ministry of Education, Science and Culture of Japan and Improvement
of Research Environment for Young Researchers from the Japan Science and
Technology Agency. Joel Moss was supported by the Intramural Research
Program, National Institutes of Health, National Heart, Lung, and Blood
Institute.
NR 55
TC 5
Z9 5
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2012
VL 80
IS 5
BP 1803
EP 1814
DI 10.1128/IAI.06164-11
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 925VX
UT WOS:000302791100021
PM 22354021
ER
PT J
AU Marcsisin, RA
Campeau, SA
Lopez, JE
Barbour, AG
AF Marcsisin, Renee A.
Campeau, Shelley A.
Lopez, Job E.
Barbour, Alan G.
TI Alp, an Arthropod-Associated Outer Membrane Protein of Borrelia Species
That Cause Relapsing Fever
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE; ANTIGENIC VARIATION; SURFACE PROTEIN; MONOCLONAL-ANTIBODY;
LINEAR PLASMIDS; MOUSE MODEL; HERMSII; BURGDORFERI; SPIROCHETE;
EXPRESSION
AB Borrelia hermsii and other relapsing fever (RF) species are noted for their highly polymorphic surface antigens, the variable major proteins (VMP). Less is known about other surface proteins of these pathogens in either their vertebrate reservoirs or arthropod vectors. To further characterize these proteins, we elicited antibodies against VMP-less cells, noted antibody reactions against whole cells and cell components, and then subjected selected antigens to mass spectroscopy for amino acid sequencing for comparison against a B. hermsii genome database. One of the derived monoclonal antibodies, H0120, agglutinated spirochetes, and in Western blot analyses, it bound to a 14-kDa protein of whole cells and their membrane fractions but not after protease treatment. A search of open reading frames of the B. hermsii genome with extracted peptides identified the 14-kDa protein with bha128, a 453-nucleotide gene of the 175-kb linear plasmid. The bha128 gene was synthesized and expressed in Escherichia coli. The protein product was bound by antibody H0120. Genes homologous to bha128 occur in the RF species Borrelia turicatae, B. duttonii, and B. recurrentis but not in Lyme disease Borrelia species or other organisms. The following findings indicated an association of BHA128, renamed Alp, with the tick environment: (i) Alp was produced at higher levels at 23 degrees C than at 34 degrees C; (ii) almost all spirochetes in tick salivary glands were bound by the H0120 antibody, but only similar to 1% of spirochetes in the blood of infected mice were bound; and (iii) infected mice produced antibodies to several B. hermsii antigens but not detectably to native or recombinant Alp.
C1 [Marcsisin, Renee A.; Campeau, Shelley A.; Barbour, Alan G.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
[Marcsisin, Renee A.; Campeau, Shelley A.; Barbour, Alan G.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Marcsisin, Renee A.; Campeau, Shelley A.; Barbour, Alan G.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92717 USA.
[Lopez, Job E.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Barbour, AG (reprint author), Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
EM abarbour@uci.edu
OI Barbour, Alan/0000-0002-0719-5248
FU Public Health Service from the National Institute of Allergy and
Infectious Diseases [AI-24424]; patent royalties; National Institutes of
Health
FX This work was supported by Public Health Service grant AI-24424 from the
National Institute of Allergy and Infectious Diseases (A.G.B.), patent
royalties (A.G.B.), and intramural funds of the National Institutes of
Health (J.E.L.).
NR 57
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2012
VL 80
IS 5
BP 1881
EP 1890
DI 10.1128/IAI.06419-11
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 925VX
UT WOS:000302791100029
PM 22354035
ER
PT J
AU Haydon, AA
Herring, AH
Prinstein, MJ
Halpern, CT
AF Haydon, Abigail A.
Herring, Amy H.
Prinstein, Mitchell J.
Halpern, Carolyn Tucker
TI Beyond Age at First Sex: Patterns of Emerging Sexual Behavior in
Adolescence and Young Adulthood
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Oral sex; Anal sex; Latent class analysis; Nationally representative;
Noncoital; Sexuality development; Adolescent sexual behavior;
Sociodemographic differences
ID ORAL SEX; INTERCOURSE; PREVALENCE; HIV; PREDICTORS; GENDER; HEALTH;
RISK; PART
AB Purpose: Although the emergence of sexual expression during adolescence and early adulthood is nearly universal, little is known about patterns of initiation.
Methods: We used latent class analysis to group 12,194 respondents from waves I and IV of the National Longitudinal Study of Adolescent Health(Add Health) into one of five classes based on variety, timing, spacing, and sequencing of oral-genital, anal, and vaginal sex. Multinomial logistic regression models, stratified by biological sex, examined associations between sociodemographic characteristics and class membership.
Results: Approximately half of respondents followed a pattern characterized predominately by initiation of vaginal sex first, average age of initiation of approximately 16 years, and spacing of >1 year between initiation of the first and second behaviors; almost one-third initiated sexual activity slightly later but reported first experiences of oral-genital and vaginal sex within the same year. Classes characterized by postponement of sexual activity, initiation of only one type of behavior, or adolescent initiation of anal sex were substantially less common. Compared with white respondents, black respondents were more likely to appear in classes characterized by initiation of vaginal sex first. Respondents from lower socioeconomic backgrounds were more likely to be in classes distinguished by early/atypical patterns of initiation.
Conclusions: A small number of typical and atypical patterns capture the emergence of sexual behavior during adolescence, but these patterns reveal complex associations among different elements of emerging sexuality that should be considered in future research. (C) 2012 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Haydon, Abigail A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, AAAS APA Execut Branch, NIH, Bethesda, MD 20892 USA.
[Halpern, Carolyn Tucker] Univ N Carolina, Dept Maternal & Child Hlth, UNC Gillings Sch Global, Chapel Hill, NC USA.
[Herring, Amy H.; Halpern, Carolyn Tucker] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, UNC Gillings Sch Global, Chapel Hill, NC USA.
[Prinstein, Mitchell J.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
RP Haydon, AA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, AAAS APA Execut Branch, NIH, 6100 Execut Blvd,Room 8B07J,MSC 7510, Bethesda, MD 20892 USA.
EM aahaydon@gmail.com
RI Prinstein, Mitchell/F-7955-2013
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [P01-HD31921, 5 R24 HD050924, R01HD57046]
FX This research uses data from Add Health, a program project directed by
Kathleen Mullan Harris and designed by J. Richard Udry, Peter S.
Bearman, and Kathleen Mullan Harris at the University of North Carolina
at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, with
cooperative funding from 23 other federal agencies and foundations.
Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle
for assistance in the original design. Information on how to obtain the
Add Health data files is available on the Add Health Web site
(http://www.cpc.unc.edu/addhealth). No direct support was received from
grant P01-HD31921 for this analysis. This research was supported by
grant 5 R24 HD050924, Carolina Population Center, awarded to the
Carolina Population Center at the University of North Carolina at Chapel
Hill by the Eunice Kennedy Shriver National Institute of Child Health
and Human Development. Effort by A.A.H. and C.T.H. was supported by
grant R01HD57046, awarded to C.T.H. of the Carolina Population Center at
the University of North Carolina at Chapel Hill by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 28
TC 17
Z9 17
U1 4
U2 28
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD MAY
PY 2012
VL 50
IS 5
BP 456
EP 463
DI 10.1016/j.jadohealth.2011.09.006
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 930HP
UT WOS:000303128600007
PM 22525108
ER
PT J
AU Agwu, AL
Siberry, GK
Ellen, J
Fleishman, JA
Rutstein, R
Gaur, AH
Korthuis, PT
Warford, R
Spector, SA
Gebo, KA
AF Agwu, Allison L.
Siberry, George K.
Ellen, Jonathan
Fleishman, John A.
Rutstein, Richard
Gaur, Aditya H.
Korthuis, P. Todd
Warford, Robert
Spector, Stephen A.
Gebo, Kelly A.
TI Predictors of Highly Active Antiretroviral Therapy Utilization for
Behaviorally HIV-1-Infected Youth: Impact of Adult Versus Pediatric
Clinical Care Site
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Adolescents; Youth; Highly active antiretroviral therapy (HAART);
Disparities; Utilization; HIV Research Network; Clinical site
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; NAIVE PATIENTS;
UNITED-STATES; SPECIAL NEEDS; ADOLESCENTS; SERVICES; ADHERENCE; COHORT;
EXPERIENCE
AB Objectives: We evaluated highly active antiretroviral therapy (HAART) utilization in youth infected with HIV through risk behaviors who met treatment criteria for HAART. We assessed the impact of receiving care at an adult or pediatric HIV clinical site on initiation and discontinuation of the first HAART regimen in behaviorally infected youth (BIY).
Methods: This was a retrospective analysis of treatment-naive BIY, aged 12-24 years, who enrolled in the HIV Research Network between 2002 and 2008 and who met criteria for HAART. The outcomes were time from meeting criteria to initiation of HAART and time to discontinuation of the first HAART regimen. Analyses were conducted using Cox proportional hazards regression.
Results: Of 287 treatment-eligible youth, 198 (69%) received HAART; of these 198 youth, 58 (29.3%) subsequently discontinued HAART. In multivariable analyses, there was no significant difference in the time between meeting treatment criteria and initiating HAART for BIY followed at adult or pediatric HIV clinical sites. However, BIY followed at adult sites discontinued HAART sooner than BIY followed at pediatric HIV clinical sites (adjusted hazard ratio [AHR]: 3.19 [1.26-8.06]).
Conclusions: Two-thirds of treatment-eligible BIY in the HIV Research Network cohort initiated HAART; however, one-third who initiated HAART discontinued it during the study period. Identifying factors associated with earlier HAART initiation and sustainability can inform interventions to enhance HAART utilization among treatment-eligible youth. The finding of earlier HAART discontinuation for youth at adult care sites deserves further study. (C) 2012 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Agwu, Allison L.] Johns Hopkins Sch Med, Div Pediat Infect Dis, Dept Pediat, Johns Hopkins Med Inst, Baltimore, MD 21287 USA.
[Agwu, Allison L.; Gebo, Kelly A.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21287 USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Baltimore, MD 21287 USA.
[Ellen, Jonathan] Johns Hopkins Sch Med, Div Adolescent Med, Baltimore, MD 21287 USA.
[Fleishman, John A.] Agcy Hlth Care Res & Qual, Ctr Financing, Rockville, MD USA.
[Rutstein, Richard] Childrens Hosp Philadelphia, Div Gen Pediat, Philadelphia, PA 19104 USA.
[Gaur, Aditya H.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Warford, Robert] St Lukes Roosevelt Hosp, New York, NY 10032 USA.
[Spector, Stephen A.] Univ Calif San Diego, Div Pediat Infect Dis, La Jolla, CA 92093 USA.
[Spector, Stephen A.] Rady Childrens Hosp, Div Pediat Infect Dis, San Diego, CA USA.
RP Agwu, AL (reprint author), Johns Hopkins Sch Med, Div Pediat Infect Dis, Dept Pediat, Johns Hopkins Med Inst, 200 N Wolfe St,Room 3145, Baltimore, MD 21287 USA.
EM ageorg10@jhmi.edu
FU Agency for Healthcare Research and Quality [290-01-0012]; National
Institute on Aging, NIH [RO1 AG026250]; Johns Hopkins University;
National Institutes of Allergy and Infectious Diseases
[1K23AI084549-01A1]; Johns Hopkins Ross Clinician scientist Award;
National Institute on Drug Abuse [K23DA019809]; Health Resources and
Services Administration, Rockville, MD; Data Coordinating Center Johns
Hopkins University; Tibotec
FX The study was supported by the Agency for Healthcare Research and
Quality (290-01-0012) and the National Institute on Aging, NIH (RO1
AG026250). K.A.G. also received support from the Johns Hopkins
University Richard Ross Clinician Scientist Award.; A.L.A. is supported
by the National Institutes of Allergy and Infectious Diseases
(1K23AI084549-01A1) and the Johns Hopkins Ross Clinician scientist
Award. P.T.K. is supported by the National Institute on Drug Abuse
(K23DA019809).; Sponsoring Agencies: Agency for Healthcare Research and
Quality, Rockville, MD (Fred Hellinger, Ph.D.; John Fleishman, Ph.D.,
Irene Fraser, Ph.D.); Health Resources and Services Administration,
Rockville, MD (Robert Mills, Ph.D.); and Data Coordinating Center Johns
Hopkins University (Richard Moore, M.D., Jeanne Keruly, C.R.N.P., Kelly
Gebo, M.D., Cindy Voss, M.A., Bonnie Cameron, M.S.).; K.A.G. has
received research funding from Tibotec.
NR 36
TC 7
Z9 8
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD MAY
PY 2012
VL 50
IS 5
BP 471
EP 477
DI 10.1016/j.jadohealth.2011.09.001
PG 7
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 930HP
UT WOS:000303128600009
PM 22525110
ER
PT J
AU Krousel-Wood, M
Muntner, P
Carson, A
Anderson, AH
Delaune, E
Cushman, WC
Cutler, JA
Piller, LB
Goforth, GA
Whelton, PK
AF Krousel-Wood, Marie
Muntner, Paul
Carson, April
Anderson, Amanda H.
Delaune, Erin
Cushman, William C.
Cutler, Jeffrey A.
Piller, Linda B.
Goforth, Gary A.
Whelton, Paul K.
TI Hypertension Control Among Newly Treated Patients Before and After
Publication of the Main ALLHAT Results and JNC 7 Guidelines
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; JOINT NATIONAL COMMITTEE;
HIGH BLOOD-PRESSURE; ALPHA-BLOCKER; 7TH REPORT; CHLORTHALIDONE;
PREVENTION; OUTCOMES; TRENDS
AB Medication prescribing practice changed following the publications of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in 2002 and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) in 2003. Few data are available on changes in hypertension control rates for patients initiating antihypertensive treatment before and after these publications. The authors compared systolic and diastolic blood pressure (SBP and DBP) levels and hypertension control (SBP <140 mm Hg and DBP <90 mm Hg) rates in patients initiating antihypertensive treatment in a large managed care organization during 2 time periods: July 1, 2001, to June 30, 2002 (n=322); and July 1, 2003, to June 30, 2004 (n=323). The blood pressure reduction associated with antihypertensive medication initiation was similar in 20012002 and 20032004 (-11.9 and -10.5 mm Hg, respectively, P=.251 for SBP; -6.9 and -5.9 mm Hg, respectively, P=.160 for DBP). The mean SBP and DBP prior to treatment were significantly lower in 20032004 vs 20012002 (145.4 vs 151.3 mm Hg, P<.001 for SBP; 87.6 vs 90.1 mm Hg, P<.002 for DBP). Hypertension control rates increased from 38.0% to 50.2% (P=.005) from 20012002 to 20032004. Lower pretreatment SBP and DBP explained hypertension control improvement over time. In this real-world clinic population, antihypertensive treatment was initiated at lower blood pressure levels following publication of ALLHAT and JNC 7, resulting in substantial improvements in hypertension control rates. J Clin Hypertens (Greenwich). 2012; 14:277283. (c) 2012 Wiley Periodicals, Inc.
C1 [Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA 70121 USA.
[Krousel-Wood, Marie] Tulane Univ, New Orleans, LA 70118 USA.
[Muntner, Paul; Carson, April] Univ Alabama, Birmingham, AL USA.
[Anderson, Amanda H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Delaune, Erin] Louisiana Off Publ Hlth, Metairie, LA USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Cutler, Jeffrey A.] NHLBI, Bethesda, MD 20892 USA.
[Piller, Linda B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Goforth, Gary A.] Montgomery Ctr Family Med, Greenwood, SC USA.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
RP Krousel-Wood, M (reprint author), Ochsner Clin Fdn, Ctr Hlth Res, 1514 Jefferson Highway, New Orleans, LA 70121 USA.
EM mawood@ochsner.org
RI Krousel-Wood, Marie Antoinette/D-4718-2011
FU National Heart, Lung, and Blood Institute [NO1-HC-35130]; Pfizer, Inc.;
GlaxoSmithKline; King; Merck; Novartis
FX The ALLHAT study was supported by a contract NO1-HC-35130 with the
National Heart, Lung, and Blood Institute. The ALLHAT investigators
acknowledge contributions of study medications supplied by Pfizer, Inc,
(amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and
Bristol-Myers Squibb (pravastatin) and financial support provided by
Pfizer, Inc.; William C. Cushman has consulted for Calpis, Daiichi
Sankyo, Gilead Colorado, Novartis, Noven, Pharmacopeia, Sanofi Aventis,
Sciele, Takeda, Theravance; has received honoraria from Bristol-Myers
Squibb, Forest Pharmaceuticals, and King; and has received research
support from GlaxoSmithKline, King, Merck, and Novartis. Amanda H.
Anderson, April Carson, Jeffrey A. Cutler, Erin Delaune, Gary A.
Goforth, Marie Krousel-Wood, Paul Muntner, Linda B. Piller, and Paul K.
Whelton have no financial interests to disclose.
NR 15
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD MAY
PY 2012
VL 14
IS 5
BP 277
EP 283
DI 10.1111/j.1751-7176.2012.00609.x
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 931DX
UT WOS:000303196500002
PM 22533653
ER
PT J
AU Menotti-Raymond, M
David, VA
Weir, BS
O'Brien, SJ
AF Menotti-Raymond, Marilyn
David, Victor A.
Weir, Bruce S.
O'Brien, Stephen J.
TI A Population Genetic Database of Cat Breeds Developed in Coordination
with a Domestic Cat STR Multiplex
SO JOURNAL OF FORENSIC SCIENCES
LA English
DT Article
DE forensic science; domestic cat; simple tandem repeat; forensic typing
system; population genetic database; cat breeds
ID RADIATION HYBRID MAP; FELIS-CATUS; TRACE EVIDENCE; TYPING SYSTEM; HAIR;
DOG; TYROSINASE; GENOME; CANINE; INDIVIDUALIZATION
AB A simple tandem repeat (STR) PCR-based typing system developed for the genetic individualization of domestic cat samples has been used to generate a population genetic database of domestic cat breeds. A panel of 10 tetranucleotide STR loci and a gender-identifying sequence tagged site (STS) were co-amplified in genomic DNA of 1043 individuals representing 38 cat breeds. The STR panel exhibits relatively high heterozygosity in cat breeds, with an average 10-locus heterozygosity of 0.71, which represents an average of 38 breed-specific heterozygosities for the 10-member panel. When the entire set of breed individuals was analyzed as a single population, a heterozygosity of 0.87 was observed. Heterozygosities obtained for the 10 loci range from 0.72 to 0.96. The power for genetic individualization of domestic cat samples of the multiplex is high, with a probability of match (pm) of 6.2E-14, using a conservative ? = 0.05.
C1 [Menotti-Raymond, Marilyn; David, Victor A.; O'Brien, Stephen J.] NCI, Lab Genom Div, Frederick, MD 21702 USA.
[Weir, Bruce S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Div, Bldg 560,Room 11-38, Frederick, MD 21702 USA.
EM raymondm@mail.nih.gov
RI Weir, Bruce/A-2894-2013
FU National Institute of Justice, Office of Justice Programs, US Department
of Justice [1999-IJ-R-A079]; NIH [GM 75091]
FX Supported by an Interagency Grant (IAA # 1999-IJ-R-A079) awarded by the
National Institute of Justice, Office of Justice Programs, US Department
of Justice to the National Cancer Institute's Laboratory of Genomic
Diversity. BSW has been supported in part by NIH grant GM 75091. Points
of view in this document are those of the authors and do not necessarily
represent the official position or policies of the US Department of
Justice.
NR 36
TC 5
Z9 5
U1 0
U2 18
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-1198
J9 J FORENSIC SCI
JI J. Forensic Sci.
PD MAY
PY 2012
VL 57
IS 3
BP 596
EP 601
DI 10.1111/j.1556-4029.2011.02040.x
PG 6
WC Medicine, Legal
SC Legal Medicine
GA 928QX
UT WOS:000302999000004
PM 22268511
ER
PT J
AU Keim, SA
Daniels, JL
Siega-Riz, AM
Dole, N
Herring, AH
Scheidt, PC
AF Keim, Sarah A.
Daniels, Julie L.
Siega-Riz, Anna Maria
Dole, Nancy
Herring, Amy H.
Scheidt, Peter C.
TI Depressive Symptoms during Pregnancy and the Concentration of Fatty
Acids in Breast Milk
SO JOURNAL OF HUMAN LACTATION
LA English
DT Article
DE depression; postpartum depression; fatty acids; pregnancy; breast milk;
introduction
ID BLOOD-CELL MEMBRANES; POSTPARTUM DEPRESSION; DOCOSAHEXAENOIC ACID;
OMEGA-3-FATTY-ACIDS; SUPPLEMENTATION; CONSUMPTION; WOMEN; ESSENTIALITY;
PREDICTORS; LIPIDS
AB The aim of the present study was to examine the association between depressive symptoms in pregnancy and the concentration of long-chain polyunsaturated fatty acids (LCPUFAs) in breast milk. Women (n = 287) enrolled in the Pregnancy, Infection, and Nutrition Study completed the Center for Epidemiologic Studies Depression Scale in pregnancy (< 20 and 24-29 weeks) and had LCPUFAs measured in breast milk (4 months postpartum). Multiple linear regression was used to examine associations between depressive symptoms and breast milk LCPUFAs. Increasing depressive symptoms at < 20 weeks were associated with lower docosahexaenoic acid concentrations (adjusted beta = -1.15, 95% confidence interval = -2.12, -0.19). No similar associations were observed with other fatty acids nor between symptoms at 24-29 weeks and LCPUFAs. Depressive symptoms, even in the subclinical range, early in pregnancy are inversely associated with breast milk docosahexaenoic acid. This may have implications for the timing of screening and interventions for perinatal depression and the nutritional value of breast milk.
C1 [Keim, Sarah A.; Daniels, Julie L.; Siega-Riz, Anna Maria; Dole, Nancy] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Keim, Sarah A.; Scheidt, Peter C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, Bethesda, MD USA.
[Daniels, Julie L.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA.
[Siega-Riz, Anna Maria] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Siega-Riz, Anna Maria; Dole, Nancy; Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
RP Keim, SA (reprint author), 700 Childrens Dr, Columbus, OH 43205 USA.
EM keim.22@osu.edu
RI Keim, Sarah/F-8929-2013;
OI Keim, Sarah/0000-0003-3490-3649; Dole, Nancy/0000-0002-2113-7984
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD37584, HD39373]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK61981, DK56350]; National Institute of
Environmental Health Sciences, National Institutes of Health
[P30ES10126]; Carolina Population Center
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: This work was supported by
grants from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (HD37584, HD39373), the National Institute
of Diabetes and Digestive and Kidney Diseases (DK61981, DK56350), and
the National Institute of Environmental Health Sciences (P30ES10126) of
the National Institutes of Health, the Carolina Population Center, and
as part of the salary-supported activities of extramural staff of the
National Institute of Child Health and Human Development.
NR 33
TC 3
Z9 3
U1 2
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0890-3344
J9 J HUM LACT
JI J. Hum. Lact.
PD MAY
PY 2012
VL 28
IS 2
BP 189
EP 195
DI 10.1177/0890334411424727
PG 7
WC Nursing; Obstetrics & Gynecology; Pediatrics
SC Nursing; Obstetrics & Gynecology; Pediatrics
GA 930GO
UT WOS:000303125900018
PM 22223516
ER
PT J
AU Sanai, N
Polley, MY
McDermott, MW
Parsa, AT
Berger, MS
AF Sanai, Nader
Polley, Mei-Yin
McDermott, Michael W.
Parsa, Andrew T.
Berger, Mitchel S.
TI Untitled RESPONSE
SO JOURNAL OF NEUROSURGERY
LA English
DT Letter
ID RESECTION; EXTENT
C1 [Sanai, Nader] Barrow Neurol Inst, Phoenix, AZ 85013 USA.
[Polley, Mei-Yin] NCI, Rockville, MD USA.
[McDermott, Michael W.; Parsa, Andrew T.; Berger, Mitchel S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Sanai, N (reprint author), Barrow Neurol Inst, Phoenix, AZ 85013 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD MAY
PY 2012
VL 116
IS 5
BP 1167
EP 1168
DI 10.3171/2011.8.JNS11637c
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 929TO
UT WOS:000303088800043
ER
PT J
AU Eid, N
Ito, Y
Otsuki, Y
Mehta, GU
Lonser, RR
Oldfield, EH
AF Eid, Nabil
Ito, Yuko
Otsuki, Yoshinori
Mehta, Gautam U.
Lonser, Russell R.
Oldfield, Edward H.
TI Cushing disease
SO JOURNAL OF NEUROSURGERY
LA English
DT Letter
ID EGYPTIANS; HISTORY
C1 [Eid, Nabil; Ito, Yuko; Otsuki, Yoshinori] Osaka Med Coll, Osaka, Japan.
[Mehta, Gautam U.; Oldfield, Edward H.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Mehta, Gautam U.; Lonser, Russell R.] NINDS, Bethesda, MD 20892 USA.
RP Eid, N (reprint author), Osaka Med Coll, Osaka, Japan.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD MAY
PY 2012
VL 116
IS 5
BP 1168
EP 1168
DI 10.3171/2012.1.JNS1224
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 929TO
UT WOS:000303088800044
PM 22424567
ER
PT J
AU Major, JM
Yu, K
Chung, CC
Weinstein, SJ
Yeager, M
Wheeler, W
Snyder, K
Wright, ME
Virtamo, J
Chanock, S
Albanes, D
AF Major, Jacqueline M.
Yu, Kai
Chung, Charles C.
Weinstein, Stephanie J.
Yeager, Meredith
Wheeler, William
Snyder, Kirk
Wright, Margaret E.
Virtamo, Jarmo
Chanock, Stephen
Albanes, Demetrius
TI Genome-Wide Association Study Identifies Three Common Variants
Associated with Serologic Response to Vitamin E Supplementation in Men
SO JOURNAL OF NUTRITION
LA English
DT Article
ID PREVENTION TRIAL SELECT; PROSTATE-CANCER RISK; ALPHA-TOCOPHEROL;
LIPID-PEROXIDATION; RECOMBINATION HOTSPOTS; LINKAGE DISEQUILIBRIUM;
COLORECTAL-CANCER; BETA-CAROTENE; PLASMA; DISEASE
AB Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating alpha-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of alpha-tocopherol (50 mg/d) and had fasting serum. alpha-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to alpha-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 x 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 X 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 X 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum alpha-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., alpha-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology. J. Nutr. 142: 866-871, 2012.
C1 [Major, Jacqueline M.; Yu, Kai; Weinstein, Stephanie J.; Chanock, Stephen; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chung, Charles C.; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA.
[Wheeler, William; Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
[Wright, Margaret E.] Univ Illinois, Dept Pathol, Chicago, IL USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Albanes, D (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015
FU NIH; National Cancer Institute; Public Health Service from National
Cancer Institute, Department of Health and Human Services [N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C]
FX Supported in part by the Intramural Research Program of the NIH and the
National Cancer Institute. Additionally, the research was supported by
Public Health Service contracts (N01-CN-45165, N01-RC-45035,
N01-RC-37004, and HHSN261201000006C) from the National Cancer Institute,
Department of Health and Human Services.
NR 46
TC 8
Z9 11
U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2012
VL 142
IS 5
BP 866
EP 871
DI 10.3945/jn.111.156349
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 929TX
UT WOS:000303089700009
PM 22437554
ER
PT J
AU Pfeiffer, CM
Hughes, JP
Lacher, DA
Bailey, RL
Berry, RJ
Zhang, M
Yetley, EA
Rader, JI
Sempos, CT
Johnson, CL
AF Pfeiffer, Christine M.
Hughes, Jeffery P.
Lacher, David A.
Bailey, Regan L.
Berry, R. J.
Zhang, Mindy
Yetley, Elizabeth A.
Rader, Jeanne I.
Sempos, Christopher T.
Johnson, Clifford L.
TI Estimation of Trends in Serum and RBC Folate in the U.S. Population from
Pre- to Postfortification Using Assay-Adjusted Data from the NHANES
1988-2010
SO JOURNAL OF NUTRITION
LA English
DT Article
ID TOTAL HOMOCYSTEINE CONCENTRATIONS; FOLIC-ACID FORTIFICATION; BIO-RAD
RADIOASSAY; UNITED-STATES; ROUND-TABLE; MICROBIOLOGIC ASSAY;
VITAMIN-B-12 STATUS; NATIONAL-HEALTH; BLOOD FOLATE; LC-MS/MS
AB The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was <= 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups, The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and post-fortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact. J. Nutr. 142: 886-893, 2012.
C1 [Pfeiffer, Christine M.; Zhang, Mindy] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Hughes, Jeffery P.; Lacher, David A.; Johnson, Clifford L.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Bailey, Regan L.; Yetley, Elizabeth A.; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Berry, R. J.] CDC, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA.
[Rader, Jeanne I.] US FDA, College Pk, MD USA.
RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
EM cpfeiffer@cdc.gov
OI Berry, Robert/0000-0002-7162-5046
FU Office of Dietary Supplements, NIH
FX Supported by funding from the Office of Dietary Supplements, NIH. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the official views or positions of the CDC and
Prevention/Agency for Toxic Substances and Disease Registry, the NIH, or
the Department of Health and Human Services.
NR 29
TC 67
Z9 70
U1 1
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2012
VL 142
IS 5
BP 886
EP 893
DI 10.3945/jn.111.156919
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 929TX
UT WOS:000303089700012
PM 22437563
ER
PT J
AU Pfeiffer, CM
Hughes, JP
Durazo-Arvizu, RA
Lacher, DA
Sempos, CT
Zhang, M
Yetley, EA
Johnson, CL
AF Pfeiffer, Christine M.
Hughes, Jeffery P.
Durazo-Arvizu, Ramon A.
Lacher, David A.
Sempos, Christopher T.
Zhang, Mindy
Yetley, Elizabeth A.
Johnson, Clifford L.
TI Changes in Measurement Procedure from a Radioassay to a Microbiologic
Assay Necessitate Adjustment of Serum and RBC Folate Concentrations in
the US Population from the NHANES 1988-2010
SO JOURNAL OF NUTRITION
LA English
DT Article
ID BIO-RAD RADIOASSAY; WHOLE-BLOOD FOLATE; LC-MS/MS; INTERNATIONAL
STANDARD; ROUND-TABLE; VITAMIN-B-12; BIOMARKERS; HISTORY
AB The NHANES measured serum and RBC folate concentrations by using a radioassay during prefortification (1988-1994) and postfortification (1999-2006) periods followed by the use of a microbiologic assay (MBA) from 2007-2010. The MBA produces higher concentrations than does the radioassay and is considered to be more accurate. To allow for accurate long-term trending (1988-2010), we evaluated different regression models (linear, piecewise linear, and fractional polynomial) to assay-adjust the radioassay results to be comparable to the MBA results. The data used to derive the regression models originated from 2 crossover studies in which the 2 assays were applied to a set of 325 serum and 171 whole-blood samples. Fractional polynomial regression of logarithmically transformed data provided the best fit for serum folate. Linear regression of logarithmically transformed whole-blood data provided an equally good fit compared with the other models and was the simplest to apply for RBC folate. Prefortification serum and RBC folate geometric mean concentrations increased after adjustment from 13.0 to 16.7 nmol/L and from 403 to 747 nmol/L, respectively. Postfortification serum folate concentrations increased from similar to 30 to similar to 43 nmol/L, and RBC folate concentrations increased from similar to 600 to similar to 1100 nmol/L after adjustment, with some variation across survey cycles. The presented regression equations allow the estimation of more accurate prevalence estimates and long-term trends in blood folate concentrations in the U.S. population by using results that are equivalent to the MBA. This information will be useful to public health officials in the United States who are dealing with folic acid fortification issues. J. Nutr. 142: 894-900, 2012.
C1 [Hughes, Jeffery P.; Lacher, David A.; Johnson, Clifford L.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Pfeiffer, Christine M.; Zhang, Mindy] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Durazo-Arvizu, Ramon A.] Loyola Univ, Dept Prevent Med & Epidemiol, Chicago, IL 60611 USA.
[Sempos, Christopher T.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
EM cpfeiffer@cdc.gov
FU Office of Dietary Supplements, NIH
FX Supported by funding from the Office of Dietary Supplements, NIH. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the official views or positions of the
CDC/Agency for Toxic Substances and Disease Registry, the NIH, or the
Department of Health and Human Services.
NR 24
TC 12
Z9 12
U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2012
VL 142
IS 5
BP 894
EP 900
DI 10.3945/jn.111.156901
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 929TX
UT WOS:000303089700013
PM 22437557
ER
PT J
AU Wang, Q
McPherron, AC
AF Wang, Qian
McPherron, Alexandra C.
TI Myostatin inhibition induces muscle fibre hypertrophy prior to satellite
cell activation
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID SKELETAL-MUSCLE; PROLONGED ABSENCE; LATENT MYOSTATIN; ADDITION IS/IS;
MYOTUBE SIZE; STEM-CELLS; MASS; GROWTH; GENE; COUNTERPOINT
AB Muscle fibres are multinucleated post-mitotic cells that can change dramatically in size during adulthood. It has been debated whether muscle fibre hypertrophy requires activation and fusion of muscle stem cells, the satellite cells. Myostatin (MSTN) is a negative regulator of skeletal muscle growth during development and in the adult, and MSTN inhibition is therefore a potential therapy for muscle wasting diseases, some of which are associated with a depletion of satellite cells. Conflicting results have been obtained in previous analyses of the role of MSTN on satellite cell quiescence. Here, we inhibited MSTN in adult mice with a soluble activin receptor type IIB and analysed the incorporation of new nuclei using 5'-bromo-2'-deoxyuridine (BrdU) labelling by isolating individual myofibres. We found that satellite cells are activated by MSTN inhibition. By varying the dose and time course for MSTN inhibition, however, we found that myofibre hypertrophy precedes the incorporation of new nuclei, and that the overall number of new nuclei is relatively low compared to the number of total myonuclei. These results reconcile some of the previous work obtained by other methods. In contrast with previous reports, we also found that Mstn null mice do not have increased satellite cell numbers during adulthood and are not resistant to sarcopaenia. Our results support a previously proposed model of hypertrophy in which hypertrophy can precede satellite cell activation. Studies of the metabolic and functional effects of postnatal MSTN inhibition are needed to determine the consequences of increasing the cytoplasm/ myonuclear ratio after MSTN inhibition.
C1 [Wang, Qian; McPherron, Alexandra C.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP McPherron, AC (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 8D12A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mcpherrona@niddk.nih.gov
OI McPherron, Alexandra/0000-0002-5875-9154
FU NIH, NIDDK; NICHD
FX This work was supported by the Intramural Research Program of the NIH,
NIDDK. We thank Kathleen Savage for helpful discussions, Tingqing Guo
for help purifying ACVR2B:Fc, Onur Kanisicak and Shahragim Tajbakhsh for
technical advice, Bryan Millis for creating the macro for the imaging
analysis, Yunping Wu for help with confocal microscopy, and Kathryn
Wagner for comments on the manuscript. The Pax7 hybridoma developed by
A. Kawakami was obtained from the Developmental Studies Hybridoma Bank
developed under the auspices of the NICHD and maintained by The
University of Iowa, Department of Biology, Iowa City, IA 52242, USA.
NR 63
TC 44
Z9 44
U1 0
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD MAY
PY 2012
VL 590
IS 9
BP 2151
EP 2165
DI 10.1113/jphysiol.2011.226001
PG 15
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 931TJ
UT WOS:000303241900010
PM 22393251
ER
PT J
AU Saha, TD
Harford, T
Goldstein, RB
Kerridge, BT
Hasin, D
AF Saha, Tulshi D.
Harford, Thomas
Goldstein, Rise B.
Kerridge, Bradley T.
Hasin, Deborah
TI Relationship of Substance Abuse to Dependence in the U.S. General
Population
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE DISORDER; DSM-IV ALCOHOL;
HEALTH INTERVIEW SURVEY; ITEM RESPONSE THEORY; DIFFERENT PSYCHOACTIVE
SUBSTANCES; DRUG-DEPENDENCE; CANNABIS DEPENDENCE; CONSTRUCT-VALIDITY;
SCHEDULE AUDADIS
AB Objective: The diagnostic categories of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for substance abuse and dependence are commonly used in clinical work and research studies, but whether abuse and dependence represent two different syndromes has been debated. The purpose of this article is to investigate the relationship of substance abuse and dependence for cannabis, cocaine, stimulants and sedatives among lifetime users of these substances in the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey conducted in 2001-2002. Method: The multiple indicators multiple causes (MIMIC) model addresses three sets of relationships: those between (1) diagnostic criteria and latent factors, (2) latent factors and covariates, and (3) criteria and covariates. This approach allows for the detection of and compensation for noninvariance of the measurement of criteria across subgroups. Results: Compared with one-factor models, two-factor models (factors roughly corresponding to abuse and dependence) fit significantly better across all substances, with abuse and dependence factors highly correlated. The MIMIC model indicated that race/ethnicity, age, income, and marital status showed some differential relationships across substance groups, although most covariates showed similar associations to dependence and abuse factors. Noninvariance of criteria measurement by demographic covariates was most pronounced for cannabis abuse and dependence criteria. Conclusions: The general relationship of abuse to dependence was consistent across substances. Results were equivocal on the value of retaining separate factors; therefore, investigating the relationships of specific genetic variants and treatment outcomes to dimensional indicators of abuse, dependence, and measures combining these criteria is warranted. Measurement of cannabis abuse and dependence criteria appears most affected by demographic characteristics. (I Stud. Alcohol Drugs, 73, 368-378, 2012)
C1 [Saha, Tulshi D.; Goldstein, Rise B.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Harford, Thomas] Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Portsmouth, NH USA.
[Kerridge, Bradley T.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
[Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
RP Saha, TD (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3083,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM sahatd@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism from the National
Institute on Drug Abuse (NIDA); National Institutes of Health/NIDA
[5F31DA025377]
FX The National Institute on Alcohol Abuse and Alcoholism funded the
National Epidemiologic Survey on Alcohol and Related Conditions with
supplemental funding from the National Institute on Drug Abuse (NIDA).
Bradley T. Kerridge was supported by National Institutes of Health/NIDA
Fellowship 5F31DA025377.
NR 48
TC 5
Z9 5
U1 3
U2 13
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD MAY
PY 2012
VL 73
IS 3
BP 368
EP 378
PG 11
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 929UQ
UT WOS:000303091600004
PM 22456242
ER
PT J
AU Frazier, JA
Giuliano, AJ
Johnson, JL
Yakutis, L
Youngstrom, EA
Breiger, D
Sikich, L
Findling, RL
McClellan, J
Hamer, RM
Vitiello, B
Lieberman, JA
Hooper, SR
AF Frazier, Jean A.
Giuliano, Anthony J.
Johnson, Jacqueline L.
Yakutis, Lauren
Youngstrom, Eric A.
Breiger, David
Sikich, Linmarie
Findling, Robert L.
McClellan, Jon
Hamer, Robert M.
Vitiello, Benedetto
Lieberman, Jeffrey A.
Hooper, Stephen R.
TI Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia
Spectrum Disorders Study
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE early-onset; schizophrenia; neurocognition; outcomes; antipsychotics
ID DOUBLE-BLIND; 1ST-EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC-DRUGS; FOLLOW-UP;
CHILDHOOD; TEOSS; TRIAL; METAANALYSIS; ADOLESCENTS; MEDICATIONS
AB Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Results: Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Conclusions: Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(5):496-505. Clinical trial registry information Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703.
C1 [Frazier, Jean A.; Giuliano, Anthony J.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Giuliano, Anthony J.] Beth Israel Deaconess Med Ctr, Massachu setts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA USA.
[Johnson, Jacqueline L.; Youngstrom, Eric A.; Sikich, Linmarie; Hamer, Robert M.; Hooper, Stephen R.] Univ N Carolina, Chapel Hill, NC USA.
[Breiger, David; McClellan, Jon] Univ Washington, Seattle, WA USA.
[Lieberman, Jeffrey A.] Columbia Univ, Coll Physicians & Surgeons, New York, NY 10027 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
RP Frazier, JA (reprint author), Univ Massachusetts, Sch Med, Biotech 1,Suite 100,365 Plantat St, Worcester, MA 01605 USA.
EM Jean.Frazier@umassmed.edu
FU National Institute of Mental Health (NIMH) [U01MH61528, U01MH61464,
U01MH62726, U01MH61355]; Maternal Child Health Bureau [MCJ379154A];
Administration on Developmental Disabilities [90DD043003]; National
Institute of Health (NIH) [M01-RR00037]; University of North Carolina
[MH01-RR00046]; Bristol-Myers Squibb; GlaxoSmithKline; Janssen; Johnson
and Johnson; Neuropharm; Otsuka American; Seaside Therapeutics; Pfizer;
Abbot; Adrenex; Alexza; American Psychiatric Press; AstraZeneca;
Biovail; Forest; Guilford Press; Johns Hopkins University Press;
KemPharm Lilly; Lundbeck; Merck; National Institutes of Health;
Novatris; Noven; Organon; Otsuka; Physicians' Post-Graduate Press;
Rhodes; Roche; Sage; Sanofi-Aventis; Schering-Plough; Sepracore;
Shionogi; Shire; Solvay; Stanley Medical Research Institute; Sunovion;
Supernus; Transcept; Validus; WebMD; Wyeth; Acadia; Allergan; Alpharma;
Cenerx; Corcept; EnabledMD; Epix; Pepper-Hamilton; Solvey; F. Hoffman-La
Roche; Pepracor (Sunovion); Targacept; Allon; Eli Lilly and Co.;
Intercellular Therapies
FX Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) is
funded by the National Institute of Mental Health (NIMH) under
cooperative agreements U01MH61528 (LS), U01MH61464 (JM), U01MH62726
(JAF), and U01MH61355 (RLF), the Maternal Child Health Bureau
(#MCJ379154A), and the Administration on Developmental Disabilities
(#90DD043003). The research was conducted in National Institute of
Health (NIH) supported Clinical Research Centers at University of
Washington (M01-RR00037) and the University of North Carolina
(MH01-RR00046). Study drugs for TEOSS were supplied by Janssen and Eli
Lilly and Co.; Dr. Frazier has received research support from or
participated in clinical trials with Bristol-Myers Squibb,
GlaxoSmithKline, Janssen, Johnson and Johnson, Neuropharm, Otsuka
American, Seaside Therapeutics, and Pfizer. Dr. Findling has received
research support from, served as a consultant for, received royalties
from, and/or served on the speakers' bureau for Abbot, Adrenex, Alexza,
American Psychiatric Press, AstraZeneca, Biovail, Bristol-Myers Squibb,
Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press,
Johnson and Johnson, KemPharm Lilly, Lundbeck, Merck, National
Institutes of Health, Neuropharm, Novatris, Noven, Organon, Otsuka,
Pfizer, Physicians' Post-Graduate Press, Rhodes, Roche, Sage,
Sanofi-Aventis, Schering-Plough, Seaside Therapeutics, Sepracore,
Shionogi, Shire, Solvay, Stanley Medical Research Institute, Sunovion,
Supernus, Transcept, Validus, WebMD, and Wyeth. Dr. Hamer has received
research support, served as a consultant for, or served on a data safety
monitoring board/independent data monitoring committee for Acadia,
Allergan, Alpharma, AstraZeneca, Cenerx, Corcept, EnabledMD, Epix,
Johnson and Johnson, Novartis, epper-Hamilton, Pfizer, SAS Institute,
Schwartz, Solvey, Sanofi-Aventis, Takeda, Winston-Strawn (a law suit
involving Forest, Lundbeck, Sun, and Caraco), and Wyeth. He and/or his
spouse are stockholders in Bristol-Myers Squibb, Amgen, Eli Lilly and
Co., Genentech, Proctor and Gamble, and Sepracor. Dr. Hooper has
received research support from and served as a consultant for Eli Lilly
and Co. Dr. Lieberman has served on the advisory boards for Bioline,
Pierre Fabre, and PsychoGenics. He has received grant support from
Allon, GlaxoSmithKline, Eli Lilly and Co., Intercellular Therapies,
Merck, Novartis, Pfizer, F. Hoffman-La Roche, Pepracor (Sunovion), and
Targacept. He holds a patent from Repligen. Dr. McClellan has received
research support from Pfizer. Dr. Sikich has received research support
from or participated in clinical trials with Bristol-Myers Squibb,
Curemark, Pfizer, Olsuka, and Seaside Therapeutics. He has served as a
consultant for Sanofi Aventis and ABT Associates. He has received
software from Posit Science. Dr. Youngstrom has served on the data
safety monitoring board for Eli Lilly and Co. He has served as a
consultant for Otsuka. He has received travel support from Bristol-Myers
Squibb. Drs. Breiger, Giuliano, Johnson, and Vitiello, and Ms. Yakutis
report no biomedical financial interests or potential conflicts of
interest.
NR 55
TC 12
Z9 12
U1 10
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAY
PY 2012
VL 51
IS 5
BP 496
EP 505
DI 10.1016/j.jaac.2012.02.001
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 932NH
UT WOS:000303297300009
PM 22525956
ER
PT J
AU Wadiwala, MF
Sonawalla, A
Kamal, AK
AF Wadiwala, Muhammad Faisal
Sonawalla, Ambreen
Kamal, Ayeesha Kamran
TI What is the role of free radical scavengers in acute stroke?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Wadiwala, Muhammad Faisal; Kamal, Ayeesha Kamran] Aga Khan Univ, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr,Med Coll, Karachi, Pakistan.
[Wadiwala, Muhammad Faisal] Aga Khan Univ, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Natl Inst Neurol Disorders & Stroke,Med Coll, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr,Med Coll, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 1
TC 1
Z9 1
U1 0
U2 0
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD MAY
PY 2012
VL 62
IS 5
BP 512
EP 513
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 930VN
UT WOS:000303170200027
PM 22755325
ER
PT J
AU Richardson, ET
Luo, R
Fink, DL
Nutman, TB
Geisse, JK
Barry, M
AF Richardson, Eugene T.
Luo, Robert
Fink, Doran L.
Nutman, Thomas B.
Geisse, John K.
Barry, Michele
TI Transient Facial Swellings in a Patient With a Remote African Travel
History
SO JOURNAL OF TRAVEL MEDICINE
LA English
DT Article
ID LOA-LOA INFECTION; LOIASIS
AB We present a case of Loa loa infection in a patient, 21 years after visiting an endemic area for only 4 days. To our knowledge, this case represents the longest time for the diagnosis of loiasis to be made post-exposure in a traveler and emphasizes that even short exposures can place travelers at risk.
C1 [Richardson, Eugene T.] Stanford Univ, Med Ctr, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Luo, Robert] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Fink, Doran L.; Nutman, Thomas B.] NIAID, Bethesda, MD 20892 USA.
[Geisse, John K.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Geisse, John K.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
RP Richardson, ET (reprint author), Stanford Univ, Med Ctr, Dept Med, Sch Med, 300 Pasteur Dr,Grant S101, Stanford, CA 94305 USA.
EM etr@stanford.edu
FU Intramural NIH HHS [Z01 AI000439-24]
NR 9
TC 6
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1195-1982
J9 J TRAVEL MED
JI J. Travel Med.
PD MAY-JUN
PY 2012
VL 19
IS 3
BP 183
EP 185
DI 10.1111/j.1708-8305.2012.00612.x
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 931EJ
UT WOS:000303197900009
PM 22530826
ER
PT J
AU Murabito, JM
Yuan, R
Lunetta, KL
AF Murabito, Joanne M.
Yuan, Rong
Lunetta, Kathryn L.
TI The Search for Longevity and Healthy Aging Genes: Insights From
Epidemiological Studies and Samples of Long-Lived Individuals
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Longevity; Genetics; Epidemiological studies
ID GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; ONSET
ALZHEIMERS-DISEASE; LOWER-EXTREMITY FUNCTION; BONE-MINERAL DENSITY;
OLDER MALE TWINS; AGED 75 YEARS; NATURAL MENOPAUSE; LIFE-SPAN;
ENVIRONMENTAL-INFLUENCES
AB Genetic factors clearly contribute to exceptional longevity and healthy aging in humans, yet the identification of the underlying genes remains a challenge. Longevity is a complex phenotype with modest heritability. Age-related phenotypes with higher heritability may have greater success in gene discovery. Candidate gene and genome-wide association studies (GWAS) for longevity have had only limited success to date. The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium conducted a meta-analysis of GWAS data for longevity, defined as survival to age 90 years or older, that identified several interesting associations but none achieved genome-wide significance. A recent GWAS of longevity conducted in the Leiden Longevity Study identified the ApoE E4 isoform as deleterious to longevity that was confirmed in an independent GWAS of long-lived individuals of German descent. Notably, no other genetic loci for longevity have been identified in these GWAS. To examine the conserved genetic mechanisms between the mouse and humans for life span, we mapped the top Cohorts for Heart and Aging Research in Genomic Epidemiology GWAS associations for longevity to the mouse chromosomal map and noted that eight of the ten top human associations were located within a previously reported mouse life-span quantitative trait loci. This work suggests that the mouse and human may share mechanisms leading to aging and that the mouse model may help speed the understanding of how genes identified in humans affect the biology of aging. We expect these ongoing collaborations and the translational work with basic scientists to accelerate the identification of genes that delay aging and promote a healthy life span.
C1 [Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Murabito, Joanne M.] Boston Univ, Dept Med, Gen Internal Med Sect, Sch Med, Boston, MA 02215 USA.
[Yuan, Rong] Jackson Lab, Aging Ctr, Bar Harbor, ME 04609 USA.
[Lunetta, Kathryn L.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM murabito@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516; Lunetta,
Kathryn/0000-0002-9268-810X
FU National Institute on Aging [R01AG29451, P30 AG038070, AG034349]
FX This work was funded through grants from the National Institute on Aging
(R01AG29451, Drs J.M.M. and K. L. L.; P30 AG038070, Drs J.M.M. and R.Y.;
AG034349, Dr R.Y.).
NR 97
TC 54
Z9 55
U1 4
U2 18
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2012
VL 67
IS 5
BP 470
EP 479
DI 10.1093/gerona/gls089
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 930SC
UT WOS:000303158600005
PM 22499766
ER
PT J
AU Pilling, LC
Harries, LW
Powell, J
Llewellyn, DJ
Ferrucci, L
Melzer, D
AF Pilling, L. C.
Harries, L. W.
Powell, J.
Llewellyn, D. J.
Ferrucci, L.
Melzer, D.
TI Genomics and Successful Aging: Grounds for Renewed Optimism?
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Longevity; Genetics; Public health
ID ALZHEIMERS-DISEASE; GENE-EXPRESSION; MACULAR DEGENERATION;
CAENORHABDITIS-ELEGANS; ARTERY-DISEASE; MESSENGER-RNA; OLDER-PEOPLE;
VARIANTS; RISK; AGE
AB Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned.
Here, we review age-related disease associated single-nucleotide polymorphisms and identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control.
Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the "fine tuning" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively.
The emerging clearer picture of the genetic architecture of age-related diseases in humans is providing new insights into the underlying pathophysiological pathways involved. Translation of genomics into new approaches to prevention, tests and treatments to extend successful aging is therefore likely in the coming decades.
C1 [Pilling, L. C.; Powell, J.; Llewellyn, D. J.; Melzer, D.] Univ Exeter, Epidemiol & Publ Hlth Grp, Peninsula Coll Med & Dent, Exeter EX4 4QJ, Devon, England.
[Harries, L. W.] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Coll Med & Dent, Exeter EX4 4QJ, Devon, England.
[Ferrucci, L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Pilling, Luke/E-4917-2013; Harries, Lorna/D-2241-2014;
OI Pilling, Luke/0000-0002-3332-8454; Melzer, David/0000-0002-0170-3838
FU Dunhill Medical Trust [R69/0208]; University of Exeter; National
Institute on Aging, U.S. National Institutes of Health
FX Work on this review was supported by an unrestricted research grant from
the Dunhill Medical Trust (Drs. M. D. and L.D.J., Grant R69/0208) and by
internal University of Exeter funding. Dr. F. L. is supported by the
Intramural Research Program, National Institute on Aging, U.S. National
Institutes of Health.
NR 77
TC 10
Z9 11
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2012
VL 67
IS 5
BP 511
EP 519
DI 10.1093/gerona/gls091
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 930SC
UT WOS:000303158600010
PM 22454374
ER
PT J
AU Leishear, K
Ferrucci, L
Lauretani, F
Boudreau, RM
Studenski, SA
Rosano, C
Abbate, R
Gori, AM
Corsi, AM
Di Iorio, A
Guralnik, JM
Bandinelli, S
Newman, AB
Strotmeyer, ES
AF Leishear, Kira
Ferrucci, Luigi
Lauretani, Fulvio
Boudreau, Robert M.
Studenski, Stephanie A.
Rosano, Caterina
Abbate, Rosanna
Gori, Anna M.
Corsi, Anna M.
Di Iorio, Angelo
Guralnik, Jack M.
Bandinelli, Stefania
Newman, Anne B.
Strotmeyer, Elsa S.
TI Vitamin B12 and Homocysteine Levels and 6-Year Change in Peripheral
Nerve Function and Neurological Signs
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Vitamin B12; Homocysteine; Peripheral nerve function; Neurological signs
ID OLDER PERSONS; PHYSICAL PERFORMANCE; QUADRICEPS STRENGTH; ELDERLY
POPULATION; BODY-COMPOSITION; WOMENS HEALTH; FOLIC-ACID; AGE;
DYSFUNCTION; NEUROPATHY
AB Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms.
Participants aged 60 years and older at baseline (n = 678; 72.2 +/- 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (< 260 pmol/L) and high Hcy (>= 13 mu mol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up.
At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (< 1 mV) and 42.1% declined to poor nerve conduction velocity (< 40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5-19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms.
High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.
C1 [Leishear, Kira; Boudreau, Robert M.; Rosano, Caterina; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Unit, Parma, Italy.
[Studenski, Stephanie A.; Newman, Anne B.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA.
[Abbate, Rosanna] Univ Florence, Dept Med & Surg Crit Care, I-50121 Florence, Italy.
[Gori, Anna M.] Thrombosis Ctr, Dept Med & Surg Crit Care, Florence, Italy.
[Gori, Anna M.] Fdn Don Carlo Gnocchi Onlus IRCCS, Ctr S Maria Ulivi, Florence, Italy.
[Corsi, Anna M.] Tuscany Reg Agcy Hlth, Florence, Italy.
[Di Iorio, Angelo] Univ G dAnnunzio, Dept Med & Sci Aging, Chieti, Italy.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Bandinelli, Stefania] Azienda Santori Firenze, Geriatr Rehabil Unit, Florence, Italy.
RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellefield Ave,Room 515, Pittsburgh, PA 15213 USA.
EM strotmeyere@edc.pitt.edu
RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; Lauretani,
Fulvio/K-5115-2016
OI Newman, Anne/0000-0002-0106-1150; Gori,
annamaria.gori@unifi.it/0000-0001-6857-5861; Rosano,
Caterina/0000-0002-0909-1506; Strotmeyer, Elsa/0000-0002-4093-6036;
Rosano, Caterina/0000-0002-4271-6010; Boudreau,
Robert/0000-0003-0162-5187; Lauretani, Fulvio/0000-0002-5287-9972
FU National Institute on Aging (NIA) [N01-AG-919413, N01-AG-821336,
R01-AG027012, R01-AG029148]; NIA, National Institutes of Health; Italian
Ministry of Health [ICS-110.1/RS97.71]
FX This work was supported by National Institute on Aging (NIA) and the
Intramural Research Program, NIA, National Institutes of Health. The
InCHIANTI study was supported as a targeted project (ICS-110.1/RS97.71)
by the Italian Ministry of Health and by the NIA (contracts
N01-AG-919413 and N01-AG-821336; grants R01-AG027012 and R01-AG029148).
NR 40
TC 15
Z9 15
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2012
VL 67
IS 5
BP 537
EP 543
DI 10.1093/gerona/glr202
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 930SC
UT WOS:000303158600013
PM 22156506
ER
PT J
AU Oki, Y
Copeland, A
Romaguera, J
Fayad, L
Fanale, M
Faria, SD
Medeiros, LJ
Ivy, P
Younes, A
AF Oki, Yasuhiro
Copeland, Amanda
Romaguera, Jorge
Fayad, Luis
Fanale, Michelle
Faria, Silvana de Castro
Medeiros, L. Jeffrey
Ivy, Percy
Younes, Anas
TI Clinical experience with the heat shock protein-90 inhibitor,
tanespimycin, in patients with relapsed lymphoma
SO LEUKEMIA & LYMPHOMA
LA English
DT Letter
ID PHASE-I TRIAL; CELL-CYCLE ARREST; ADVANCED CANCER; ALK EXPRESSION;
KINASE; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; COMPLEX; AKT
C1 [Oki, Yasuhiro; Copeland, Amanda; Romaguera, Jorge; Fayad, Luis; Fanale, Michelle; Younes, Anas] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA.
[Faria, Silvana de Castro] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Imaging, Houston, TX 77030 USA.
[Medeiros, L. Jeffrey] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA.
[Ivy, Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Younes, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Unit 429,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM ayounes@mdanderson.org
FU NCI NIH HHS [5 R21 CA117070-02]
NR 14
TC 7
Z9 7
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD MAY
PY 2012
VL 53
IS 5
BP 990
EP 992
DI 10.3109/10428194.2011.631236
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA 929NA
UT WOS:000303070900040
PM 21988665
ER
PT J
AU Sastalla, I
Leppla, SH
AF Sastalla, Inka
Leppla, Stephen H.
TI Occurrence, recognition, and reversion of spontaneous,
sporulation-deficient Bacillus anthracis mutants that arise during
laboratory culture
SO MICROBES AND INFECTION
LA English
DT Review
DE Bacillus anthracis; Sporulation; spo0A; Mutation; Amerithrax
ID PROTECTIVE ANTIGEN; ILLEGITIMATE RECOMBINATION; EXPERIMENTAL
POPULATIONS; SUBTILIS; CLONING; STRAIN; GENE; BACTERIOPHAGE; SEQUENCE;
IDENTIFICATION
AB Bacillus anthracis is a spore-forming, soil-dwelling bacterium. This review describes the occurrence of spontaneous mutations leading to loss of sporulation and the selective pressures that can lead to their enrichment. We also discuss recognition of the associated phenotypes on solid medium, thereby allowing researchers to employ measures that either prevent or favor selection of sporulation-deficient mutants. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Sastalla, Inka; Leppla, Stephen H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Leppla, SH (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 33, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases.
NR 42
TC 2
Z9 2
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD MAY
PY 2012
VL 14
IS 5
BP 387
EP 391
DI 10.1016/j.micinf.2011.11.009
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 932CS
UT WOS:000303268600001
PM 22166343
ER
PT J
AU Moayeri, M
Sastalla, I
Leppla, SH
AF Moayeri, Mahtab
Sastalla, Inka
Leppla, Stephen H.
TI Anthrax and the inflammasome
SO MICROBES AND INFECTION
LA English
DT Review
DE Anthrax lethal toxin; Inflammasome; Caspase-1; Nlrp1; Nlrp1b; Bacillus
anthracis
ID TOXIN-INDUCED CYTOLYSIS; LETHAL FACTOR CLEAVES; END RULE PATHWAY;
BACILLUS-ANTHRACIS; CELL-DEATH; CASPASE-1 ACTIVATION; MURINE
MACROPHAGES; EDEMA TOXIN; PROTECTIVE ANTIGEN; KINASE-KINASE
AB Anthrax lethal toxin (LT), a major virulence determinant of anthrax disease, induces vascular collapse in mice and rats. LT activates the Nlrp1 inflammasome in macrophages and dendritic cells, resulting in caspase-1 activation, IL-1 beta and IL-18 maturation and a rapid cell death (pyroptosis). This review presents the current understanding of LT-induced activation of Nlrp1 in cells and its consequences for toxin-mediated effects in rodent toxin and spore challenge models. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Moayeri, Mahtab; Sastalla, Inka; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Moayeri, M (reprint author), NIAID, Lab Bacterial Dis, NIH, Bldg 33,Room 1W20B, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov; sastallai@niaid.nih.gov; sleppla@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases.
NR 78
TC 28
Z9 29
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
EI 1769-714X
J9 MICROBES INFECT
JI Microbes Infect.
PD MAY
PY 2012
VL 14
IS 5
BP 392
EP 400
DI 10.1016/j.micinf.2011.12.005
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 932CS
UT WOS:000303268600002
PM 22207185
ER
PT J
AU Mage, M
Dolan, M
Wang, R
Boyd, L
Revilleza, M
Robinson, H
Natarajan, K
Myers, N
Hansen, T
Margulies, D
AF Mage, Michael
Dolan, Michael
Wang, Rui
Boyd, Lisa
Revilleza, Maria
Robinson, Howard
Natarajan, Kannan
Myers, Nancy
Hansen, Ted
Margulies, David
TI The peptide-receptive transition state of MHC-I molecules: Insight from
structure and molecular dynamics
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 7th Biannual Workshop on Antigen Presentation
CY APR 24-27, 2012
CL Amsterdam, NETHERLANDS
C1 [Mage, Michael; Wang, Rui; Boyd, Lisa; Revilleza, Maria; Natarajan, Kannan; Margulies, David] NIAID, NIH, Immunol Lab, Mol Biol Sect, Bethesda, MD USA.
[Dolan, Michael] NIAID, NIH, Bioinformat & Computat Biosci Branch, Computat Biol Sect, Bethesda, MD USA.
[Robinson, Howard] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Myers, Nancy; Hansen, Ted] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD MAY
PY 2012
VL 51
IS 1
BP 24
EP 24
DI 10.1016/j.molimm.2012.02.064
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 934FT
UT WOS:000303429800059
ER
PT J
AU Roche, P
Furuta, K
Ishido, S
AF Roche, Paul
Furuta, Kazuyuki
Ishido, Satoshi
TI MHC-II crosslinking promotes lipid-raft dependent MHC-II clustering,
endocytosis, and degradation in dendritic cells
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 7th Biannual Workshop on Antigen Presentation
CY APR 24-27, 2012
CL Amsterdam, NETHERLANDS
C1 [Roche, Paul; Furuta, Kazuyuki] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD MAY
PY 2012
VL 51
IS 1
BP 29
EP 29
DI 10.1016/j.molimm.2012.02.078
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 934FT
UT WOS:000303429800072
ER
PT J
AU Yewdell, J
David, A
Dolan, B
Lu, XJ
Bennink, J
AF Yewdell, Jonathan
David, Alexandre
Dolan, Brian
Lu, Xiuju
Bennink, Jack
TI Will wonders never cease? Unraveling the Intricacies of the class I
processing pathway
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 7th Biannual Workshop on Antigen Presentation
CY APR 24-27, 2012
CL Amsterdam, NETHERLANDS
C1 [Yewdell, Jonathan; David, Alexandre; Dolan, Brian; Lu, Xiuju; Bennink, Jack] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD MAY
PY 2012
VL 51
IS 1
BP 37
EP 37
DI 10.1016/j.molimm.2012.02.105
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 934FT
UT WOS:000303429800099
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, D.
Volkow, N. D.
TI Aging and functional brain networks
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE aging; Alzheimer's disease; functional connectomes; connectivity
ID ALZHEIMERS-DISEASE; DOPAMINE ACTIVITY; WORKING-MEMORY; CONNECTIVITY;
DECLINE; AGE; IMPAIRMENT; PATTERNS; RESERVE; FMRI
AB Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging. Molecular Psychiatry (2012) 17, 549-558; doi:10.1038/mp.2011.81; published online 5 July 2011
C1 [Tomasi, D.; Volkow, N. D.] NIAAA, Bethesda, MD USA.
[Volkow, N. D.] NIDA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Lab Neuroimaging LNI NIAAA, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX This study was supported by the National Institutes of Alcohol Abuse and
Alcoholism (2RO1AA09481).
NR 56
TC 133
Z9 135
U1 5
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD MAY
PY 2012
VL 17
IS 5
BP 549
EP 558
DI 10.1038/mp.2011.81
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 930BN
UT WOS:000303110800010
ER
PT J
AU Lorincz, O
Toke, ER
Somogyi, E
Horkay, F
Chandran, PL
Douglas, JF
Szebeni, J
Lisziewicz, J
AF Lorincz, Orsolya
Toke, Eniko R.
Somogyi, Eszter
Horkay, Ferenc
Chandran, Preethi L.
Douglas, Jack F.
Szebeni, Janos
Lisziewicz, Julianna
TI Structure and biological activity of pathogen-like synthetic
nanomedicines
SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
LA English
DT Article
DE Vaccine; Immunotherapy; Immunity; DermaVir
ID GENE DELIVERY; COMPLEMENT ACTIVATION; POTENTIAL BARRIER; CATIONIC
LIPIDS; PLASMID DNA; IN-VITRO; COMPLEXES; HYPERSENSITIVITY;
POLYETHYLENIMINE; DERMAVIR
AB Here we characterize the structure, stability and intracellular mode of action of DermaVir nanomedicine that is under clinical development for the treatment of HIV/AIDS. This nanomedicine comprises pathogen-like pDNA/PEIm nanoparticles (NPs) having the structure and function resembling spherical viruses that naturally evolved to deliver nucleic acids to the cells. Atomic force microscopy demonstrated spherical 100 - 200 nm NPs with a smooth polymer surface protecting the pDNA in the core. Optical absorption determined both the NP structural stability and biological activity relevant to their ability to escape from the endosome and release the pDNA at the nucleus. Salt, pH and temperature influence nanomedicine shelf-life and intracellular stability. This approach facilitates the development of diverse polyplex nanomedicines where the delivered pDNA-expressed antigens induce immune responses to kill infected cells.
From the Clinical Editor: The authors investigated DermaVir nanomedicine comprised of pathogen-like pDNA/PEIm nanoparticles with structure and function resembling spherical viruses. DermaVir delivery of pDNA expresses antigens that induce immune responses to kill HIV infected cells. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Lorincz, Orsolya; Toke, Eniko R.; Somogyi, Eszter; Lisziewicz, Julianna] Genet Immun Kft, H-1045 Budapest, Hungary.
[Horkay, Ferenc; Chandran, Preethi L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD USA.
[Douglas, Jack F.] NIST, Div Polymers, Gaithersburg, MD 20899 USA.
[Szebeni, Janos] Bay Zoltan Fdn Appl Res, Nanomed Res & Educ Ctr, H-1089 Budapest, Hungary.
[Szebeni, Janos] Semmelweis Univ, H-1089 Budapest, Hungary.
[Lisziewicz, Julianna] Genet Immun LLC, Mclean, VA USA.
RP Lisziewicz, J (reprint author), Genet Immun Kft, Berlini U 47-49, H-1045 Budapest, Hungary.
EM lisziewj@geneticimmunity.com
FU NICHD, NIH; NKTH [CARPA777]; [HIKC05]; [DVCLIN01]
FX Dr. Julianna Lisziewicz holds shares in Genetic Immunity. This work was
supported by grants: HIKC05 and DVCLIN01 announced by the National
Office for Research and Technology (NKTH) in Hungary. Ferene Horkay and
Preethi L. Chandran acknowledge the support of the Intramural Research
Program of the NICHD, NIH. Janos Szebeni acknowledges the grant supports
FP7 "Anticarb," NKTH CARPA777.
NR 40
TC 15
Z9 15
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1549-9634
J9 NANOMED-NANOTECHNOL
JI Nanomed.-Nanotechnol. Biol. Med.
PD MAY
PY 2012
VL 8
IS 4
BP 497
EP 506
DI 10.1016/j.nano.2011.07.013
PG 10
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 930QI
UT WOS:000303153800014
PM 21839051
ER
PT J
AU Eskan, MA
Jotwani, R
Abe, T
Chmelar, J
Lim, JH
Liang, S
Ciero, PA
Krauss, JL
Li, FG
Rauner, M
Hofbauer, LC
Choi, EY
Chung, KJ
Hashim, A
Curtis, MA
Chavakis, T
Hajishengallis, G
AF Eskan, Mehmet A.
Jotwani, Ravi
Abe, Toshiharu
Chmelar, Jindrich
Lim, Jong-Hyung
Liang, Shuang
Ciero, Paul A.
Krauss, Jennifer L.
Li, Fenge
Rauner, Martina
Hofbauer, Lorenz C.
Choi, Eun Young
Chung, Kyoung-Jin
Hashim, Ahmed
Curtis, Michael A.
Chavakis, Triantafyllos
Hajishengallis, George
TI The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated
inflammatory bone loss
SO NATURE IMMUNOLOGY
LA English
DT Article
ID PERIODONTAL-DISEASES; IL-17 RECEPTOR; ADHESION CASCADE; INNATE IMMUNITY;
IN-VITRO; T-CELLS; NEUTROPHILS; MICE; RECRUITMENT; INTERLEUKIN-17
AB Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.
C1 [Eskan, Mehmet A.; Jotwani, Ravi; Abe, Toshiharu; Liang, Shuang; Ciero, Paul A.; Krauss, Jennifer L.; Li, Fenge; Hajishengallis, George] Univ Louisville, Sch Dent, Ctr Oral Hlth & Syst Dis, Louisville, KY 40292 USA.
[Chmelar, Jindrich; Lim, Jong-Hyung; Choi, Eun Young; Chung, Kyoung-Jin; Chavakis, Triantafyllos] Tech Univ Dresden, Dept Med, Div Vasc Inflammat Diabet & Kidney, D-01062 Dresden, Germany.
[Chmelar, Jindrich; Lim, Jong-Hyung; Choi, Eun Young; Chung, Kyoung-Jin; Chavakis, Triantafyllos] Tech Univ Dresden, Inst Physiol, D-01062 Dresden, Germany.
[Rauner, Martina; Hofbauer, Lorenz C.] Tech Univ Dresden, Dept Med, Div Endocrinol Diabet & Bone Dis, D-01062 Dresden, Germany.
[Choi, Eun Young] Univ Ulsan, Grad Sch, Dept Med, Seoul, South Korea.
[Choi, Eun Young; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Hashim, Ahmed; Curtis, Michael A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Immunol & Infect Dis, Blizard Inst, London, England.
[Eskan, Mehmet A.; Hajishengallis, George] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA.
RP Hajishengallis, G (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
EM geoh@upenn.edu
RI Rauner, Martina/A-1665-2015; Hofbauer, Lorenz/G-2490-2010
OI Hofbauer, Lorenz/0000-0002-8691-8423
FU US National Institutes of Health, National Cancer Institute; Deutsche
Forschungsgemeinschaft [SFB655/TPB10, CH279/5-1]; Medical Faculty of the
University of Dresden (MedDrive); Medical Research Council UK
[G0900408]; US National Institutes of Health [DE015254, DE018292,
DE021580, DE021685]
FX We thank T. Quertermous and R. Kundu (Stanford University School of
Medicine) for Edil3-/- mice; C. M. Ballantyne (Baylor College
of Medicine) for Itgal-/- mice; Amgen for
Il17ra-/- mice and mAb to IL-17 (M210); Novartis for LFA878;
Valentis for Del-1; and S. Gaffen for discussions and advice. Supported
by the Intramural Research Program of the US National Institutes of
Health, the National Cancer Institute (T. C.), Deutsche
Forschungsgemeinschaft (SFB655/TPB10 and CH279/5-1 to T. C.), the
Medical Faculty of the University of Dresden (MedDrive to K.-J.C.), the
Medical Research Council UK (G0900408 to M. A. C.) and the Extramural
Research Program of the US National Institutes of Health (DE015254,
DE018292, DE021580 and DE021685 to G.H.).
NR 48
TC 123
Z9 130
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAY
PY 2012
VL 13
IS 5
BP 465
EP U64
DI 10.1038/ni.2260
PG 10
WC Immunology
SC Immunology
GA 929GD
UT WOS:000303048400010
PM 22447028
ER
PT J
AU Dickendesher, TL
Baldwin, KT
Mironova, YA
Koriyama, Y
Raiker, SJ
Askew, KL
Wood, A
Geoffroy, CG
Zheng, BH
Liepmann, CD
Katagiri, Y
Benowitz, LI
Geller, HM
Giger, RJ
AF Dickendesher, Travis L.
Baldwin, Katherine T.
Mironova, Yevgeniya A.
Koriyama, Yoshiki
Raiker, Stephen J.
Askew, Kim L.
Wood, Andrew
Geoffroy, Cedric G.
Zheng, Binhai
Liepmann, Claire D.
Katagiri, Yasuhiro
Benowitz, Larry I.
Geller, Herbert M.
Giger, Roman J.
TI NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans
SO NATURE NEUROSCIENCE
LA English
DT Article
ID SPINAL-CORD-INJURY; TYROSINE-PHOSPHATASE-SIGMA; RETINAL GANGLION-CELLS;
OLIGODENDROCYTE-MYELIN GLYCOPROTEIN; CORTICOSPINAL TRACT REGENERATION;
OPTIC-NERVE REGENERATION; NOGO RECEPTOR; AXON REGENERATION; NEURITE
GROWTH; FUNCTIONAL RECEPTOR
AB In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as Rtn4r, Rtn4rI2 and Rtn4rI1, respectively), but not single mutants, showed enhanced axonal regeneration following retro-orbital optic nerve crush injury. The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptp sigma (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.
C1 [Dickendesher, Travis L.; Giger, Roman J.] Univ Michigan, Sch Med, Neurosci Program, Ann Arbor, MI 48109 USA.
[Dickendesher, Travis L.; Baldwin, Katherine T.; Mironova, Yevgeniya A.; Raiker, Stephen J.; Giger, Roman J.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA.
[Baldwin, Katherine T.; Mironova, Yevgeniya A.; Giger, Roman J.] Univ Michigan, Sch Med, Cellular & Mol Biol Program, Ann Arbor, MI USA.
[Koriyama, Yoshiki; Benowitz, Larry I.] Harvard Univ, Childrens Hosp, Sch Med, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Koriyama, Yoshiki; Benowitz, Larry I.] Harvard Univ, Childrens Hosp, Sch Med, Lab Neurosci Res Neurosurg, Boston, MA 02115 USA.
[Koriyama, Yoshiki; Benowitz, Larry I.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Raiker, Stephen J.] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Rochester, NY USA.
[Askew, Kim L.; Wood, Andrew] Pfizer Global Res & Dev, Neurosci Res Unit, Groton, CT USA.
[Geoffroy, Cedric G.; Zheng, Binhai] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA.
[Liepmann, Claire D.; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Benowitz, Larry I.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
[Giger, Roman J.] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA.
RP Giger, RJ (reprint author), Univ Michigan, Sch Med, Neurosci Program, Ann Arbor, MI 48109 USA.
EM rgiger@umich.edu
OI Geller, Herbert/0000-0002-7048-6144
FU Neuroscience Training Grant [T32EY017878]; University of Michigan;
Cellular and Molecular Biology Training Grant [T32GM007315]; National
Research Service Award Ruth Kirschstein Fellowship [F31NS061589]; New
York State Spinal Cord Injury Research Program; Dr. Miriam and Sheldon
G. Adelson Medical Foundation on Neural Repair and Rehabilitation; US
Department of Veterans Affairs [1I0IRX000229-01]; National Institute of
Neurological Disorders and Stroke [R56NSO47333]; National Eye Institute
FX We thank M. Tremblay for Rptp sigma-/- mice, M. Greenberg for
Ngr3-/- mice, B. Pierchala for p75NTR-/- mice, B.
Bates, D. Howland and M.L. Mercado for their assistance in the
generation and initial analysis of Ngr1-/-;
Ngr2-/-; Ngr3-/- mice, U. Rutishauser for Endo-N,
D. Figge and Y. Yasui for assistance in ELISA binding assays, Y. Yin for
training in optic nerve surgery, Y. Duan for generation of the RPTP
sigma(Igl-3)-Fc construct,). Barbieri for technical assistance and M.M.
Zaleska for project administration. This work was supported by
Neuroscience Training Grant T32EY017878 and the University of Michigan
Rackham Merit Fellowship (T.L.D.), Cellular and Molecular Biology
Training Grant T32GM007315 (K.T.B. and Y.A.M.), National Research
Service Award Ruth Kirschstein Fellowship F31NS061589 (S.J.R.), the New
York State Spinal Cord Injury Research Program, the Dr. Miriam and
Sheldon G. Adelson Medical Foundation on Neural Repair and
Rehabilitation, the US Department of Veterans Affairs (1I0IRX000229-01),
the National Institute of Neurological Disorders and Stroke
(R56NSO47333, R.J.G.) and the National Eye Institute (L.I.B.).
NR 48
TC 155
Z9 158
U1 4
U2 31
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAY
PY 2012
VL 15
IS 5
BP 703
EP 712
DI 10.1038/nn.3070
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 932DI
UT WOS:000303270200014
PM 22406547
ER
PT J
AU Hanover, JA
Krause, MW
Love, DC
AF Hanover, John A.
Krause, Michael W.
Love, Dona C.
TI Bittersweet memories: linking metabolism to epigenetics through
O-GlcNAcylation
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID EMBRYONIC STEM-CELLS; LINKED GLCNAC TRANSFERASE;
BETA-N-ACETYLGLUCOSAMINIDASE; THRIFTY PHENOTYPE HYPOTHESIS; POLYCOMB
GROUP GENES; INSULIN-RESISTANCE; CAENORHABDITIS-ELEGANS;
TETRATRICOPEPTIDE REPEATS; DROSOPHILA-MELANOGASTER; PROTEIN
GLYCOSYLATION
AB O-GlcNAcylation, which is a nutrient-sensitive sugar modification, participates in the epigenetic regulation of gene expression. The enzymes involved in O-linked beta-D-N-acetylglucosamine (O-GlcNAc) cycling - O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) - target key transcriptional and epigenetic regulators including RNA polymerase II, histones, histone deacetylase complexes and members of the Polycomb and Trithorax groups. Thus, O-GlcNAc cycling may serve as a homeostatic mechanism linking nutrient availability to higher-order chromatin organization. In response to nutrient availability, O-GlcNAcylation is poised to influence X chromosome inactivation and genetic imprinting, as well as embryonic development. The wide range of physiological functions regulated by O-GlcNAc cycling suggests an unexplored nexus between epigenetic regulation in disease and nutrient availability.
C1 [Hanover, John A.; Love, Dona C.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD USA.
RP Hanover, JA (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov; michaelkr@niddk.nih.gov; donalove@mail.nih.gov
OI Krause, Michael/0000-0001-6127-3940
FU National Institutes of Diabetes and Digestive and Kidney Diseases
FX The authors wish to thank P. Wang, M. Bond, T. Fukushige and K. Harwood
for helpful discussions. The work was supported by National Institutes
of Diabetes and Digestive and Kidney Diseases intramural funds.
NR 112
TC 162
Z9 162
U1 5
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
EI 1471-0080
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD MAY
PY 2012
VL 13
IS 5
BP 312
EP 321
DI 10.1038/nrm3334
PG 10
WC Cell Biology
SC Cell Biology
GA 930BW
UT WOS:000303111800014
PM 22522719
ER
PT J
AU Becker, RE
Greig, N
AF Becker, Robert E.
Greig, N.
TI ARE WE READY WITH A NEW TRIAL DESIGN?
SO NEUROBIOLOGY OF AGING
LA English
DT Meeting Abstract
CT 12th International Stockholm/Springfield Symposium on Advances in
Alzheimer Therapy
CY MAY 09-12, 2012
CL Stockholm, SWEDEN
C1 [Becker, Robert E.] Aristea Translat Med Corp, S Freeport, ME USA.
[Greig, N.] NIA, Baltimore, MD 21224 USA.
EM rebecker2008@comcast.net
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 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2012
VL 33
SU 1
MA 5
BP S3
EP S3
PG 1
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 930NX
UT WOS:000303147200006
ER
PT J
AU Yang, J
Eliasson, B
Smith, U
Cushman, SW
Sherman, AS
AF Yang, Jian
Eliasson, Bjorn
Smith, Ulf
Cushman, Samuel W.
Sherman, Arthur S.
TI The Size of Large Adipose Cells Is a Predictor of Insulin Resistance in
First-Degree Relatives of Type 2 Diabetic Patients
SO OBESITY
LA English
DT Article
ID ABDOMINAL ADIPOCYTE SIZE; FAT-CELLS; HUMAN-DISEASE; TISSUE; OBESITY;
EXPRESSION; INFLAMMATION; RECRUITMENT; SECRETION; NUMBER
AB Early studies reported that the size of adipose cells correlates with insulin resistance. However, a recent study comparing moderately obese, sensitive and resistant subjects, with comparable BMI (similar to 30), did not detect any significant difference in the size of the large cells, but rather a smaller proportion of large cells in the resistant subjects, suggesting impaired adipogenesis. We hypothesize that a decreased proportion, rather than the size, of large adipose cells is also associated with insulin resistance in first-degree relatives of type 2 diabetic patients. Thirty-five leaner (BMI 18-34) subjects who were relatively healthy were recruited. Insulin sensitivity was measured by the euglycemic, hyperinsulinemic clamp. Needle biopsies of abdominal subcutaneous fat were assayed for adipose cell size by fitting the cell size distribution with two exponentials and a Gaussian function. The fraction of large cells was defined as the area of the Gaussian peak and the size of the large cells was defined as its center (c(p)). Glucose infusion rate (GIR) and c were negatively correlated, but insulin sensitivity and the proportion of large cells were not correlated. BMI and c(p) were also strongly correlated, but a relationship of modest correlation between the cell size and insulin resistance was still significant after correcting for BMI. In contrast to moderately obese subjects, in the first-degree relatives of type 2 diabetic patients both BMI and the size of the large adipose cells predict the degree of insulin resistance; no correlation is found between the proportion of large adipose cells and insulin resistance.
C1 [Sherman, Arthur S.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Yang, Jian; Cushman, Samuel W.] NIDDK, Diabet Branch, NIH, Bethesda, MD USA.
[Yang, Jian] Univ S Alabama, Coll Med, Dept Physiol, Mobile, AL 36688 USA.
[Eliasson, Bjorn; Smith, Ulf] Univ Gothenburg, Dept Mol & Clin Med, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
RP Sherman, AS (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM jyang@usouthal.edu; arthur.sherman@nih.gov
OI Eliasson, Bjorn/0000-0003-2569-4160
FU Swedish Research Council; Novo Nordisk Foundation; Swedish Diabetes
Association; NIDDK, NIH
FX B.E. and U.S. were supported by the Swedish Research Council, the Novo
Nordisk Foundation, and the Swedish Diabetes Association. J. Y., S. C.,
and A. S. were supported by the Intramural Research Program of NIDDK,
NIH. We thank Junghyo Jo and Vipul Periwal (LBM, NIDDK) for the
insightful comments. We thank Tracey McLaughlin for permission to
reanalyze the data from a previous study.
NR 34
TC 29
Z9 29
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2012
VL 20
IS 5
BP 932
EP 938
DI 10.1038/oby.2011.371
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 932ND
UT WOS:000303296900002
PM 22240722
ER
PT J
AU Diamond, MP
Kruger, M
Santoro, N
Zhang, HP
Casson, P
Schlaff, W
Coutifaris, C
Brzyski, R
Christman, G
Carr, BR
McGovern, PG
Cataldo, NA
Steinkampf, MP
Gosman, GG
Nestler, JE
Carson, S
Myers, EE
Eisenberg, E
Legro, RS
AF Diamond, Michael P.
Kruger, Michael
Santoro, Nanette
Zhang, Heping
Casson, Peter
Schlaff, William
Coutifaris, Christos
Brzyski, Robert
Christman, Gregory
Carr, Bruce R.
McGovern, Peter G.
Cataldo, Nicholas A.
Steinkampf, Michael P.
Gosman, Gabriella G.
Nestler, John E.
Carson, Sandra
Myers, Evan E.
Eisenberg, Esther
Legro, Richard S.
CA Eunice Kennedy Shriver Natl Inst C
TI Endometrial Shedding Effect on Conception and Live Birth in Women With
Polycystic Ovary Syndrome
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 22, 2012
CL San Diego, CA
SP Soc Gynecol Invest
ID HORMONE PULSE-GENERATOR; ANDROGEN RECEPTOR EXPRESSION; HOMEOSTASIS
MODEL; GENE-EXPRESSION; MENSTRUAL-CYCLE; CLINICAL-TRIALS; PROGESTERONE;
SENSITIVITY; INFERTILITY; INHIBITION
AB OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS).
METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed).
RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001).
CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS.
C1 Wayne State Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Detroit, MI USA.
Univ Colorado, Dept Obstet & Gynecol, Aurora, CO USA.
Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
Univ Vermont, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Burlington, VT USA.
Univ Colorado Denver, Sch Med, Dept Obstet & Gynecol, Adv Reprod Med,Sect Reprod Endocrinol & Infertil, Aurora, CO USA.
Univ Penn, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Med Ctr, Philadelphia, PA 19104 USA.
Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA.
Univ Alabama, Birmingham, AL USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Virginia Commonwealth Univ, Dept Med, Sch Med, Richmond, VA 23298 USA.
Brown Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Warren Alpert Med Sch, Providence, RI 02912 USA.
Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Med Network, Reprod Sci Branch, Populat Res Ctr,NIH, Bethesda, MD USA.
Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Coll Med, Hershey, PA 17033 USA.
RP Diamond, MP (reprint author), 60 W Hancock, Detroit, MI 48201 USA.
EM mdiamond@med.wayne.edu
OI Diamond, Michael/0000-0001-6353-4489
FU NCRR NIH HHS [C06 RR016499, M01 RR000056, M01 RR010732, M01RR00056,
M01RR10732]; NICHD NIH HHS [HD55925, HD055942, HD055944, HD27011,
HD27049, HD33172, HD38988, HD38992, HD38997, HD38998, HD38999, HD39005,
HD55936, U01 HD038997, U10 HD027011, U10 HD027049, U10 HD033172, U10
HD038988, U10 HD038992, U10 HD038998, U10 HD038999, U10 HD039005, U10
HD055925, U10 HD055936, U10 HD055942, U10 HD055944]
NR 33
TC 22
Z9 25
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2012
VL 119
IS 5
BP 902
EP 908
DI 10.1097/AOG.0b013e31824da35c
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 930OW
UT WOS:000303150000004
PM 22525900
ER
PT J
AU Gabbe, SG
Landon, MB
Warren-Boulton, E
Fradkin, J
AF Gabbe, Steven G.
Landon, Mark B.
Warren-Boulton, Elizabeth
Fradkin, Judith
TI Promoting Health After Gestational Diabetes: A National Diabetes
Education Program Call to Action Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Gabbe, Steven G.; Landon, Mark B.] Ohio State Univ, Wexner Med Ctr, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Warren-Boulton, Elizabeth] Hager Sharp Inc, Washington, DC USA.
[Fradkin, Judith] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
RP Gabbe, SG (reprint author), Ohio State Univ, Wexner Med Ctr, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
NR 1
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2012
VL 119
IS 5
BP 1055
EP 1055
DI 10.1097/AOG.0b013e318253aa80
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 930OW
UT WOS:000303150000027
ER
PT J
AU Wei, H
Xiang, LM
Wayne, AS
Chertov, O
FitzGerald, DJ
Bera, TK
Pastan, I
AF Wei, Hui
Xiang, Laiman
Wayne, Alan S.
Chertov, Oleg
FitzGerald, David J.
Bera, Tapan K.
Pastan, Ira
TI Immunotoxin resistance via reversible methylation of the DPH4 promoter
is a unique survival strategy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA methylation; drug resistance; ADP-ribosylation; diphthamide
synthesis; epigenetic regulation
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOLOGIC MALIGNANCIES; DNA METHYLATION;
MYELODYSPLASTIC SYNDROME; RECOMBINANT IMMUNOTOXIN; RFB4(DSFV)-PE38 BL22;
PSEUDOMONAS EXOTOXIN; LYMPHOCYTIC-LEUKEMIA; GROUP-B; CANCER
AB HA22 is a recombinant immunotoxin composed of an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A. HA22 produced a high rate of complete remissions in drug-resistant hairy cell leukemia and has a lower response rate in pediatric acute lymphoblastic leukemia (ALL). To understand why patients with ALL have poorer responses, we isolated an ALL cell line that is resistant to killing by HA22. The resistance is unstable; without HA22 the cells revert to HA22 sensitivity in 4 mo. We showed that in the resistant cell line, HA22 is unable to ADP ribosylate and inactivate elongation factor-2 (EF2), owing to a low level of DPH4 mRNA and protein, which prevents diphthamide biosynthesis and renders EF2 refractory to HA22. Analysis of the promoter region of the DPH4 gene shows that the CpG island was hypomethylated in the HA22-sensitive cells, heavily methylated in the resistant cells, and reverted to low methylation in the revertant cells. Our data show that immunotoxin resistance is associated with reversible CpG island methylation and silencing of DPH4 gene transcription. Incubation of sensitive cells with the methylation inhibitor 5-azacytidine prevented the emergence of resistant cells, suggesting that this agent in combination with HA22 may be useful in the treatment of some cases of ALL.
C1 [Wei, Hui; Xiang, Laiman; Wayne, Alan S.; FitzGerald, David J.; Bera, Tapan K.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chertov, Oleg] NCI, Prot Chem Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; [HHSN261200800001E]
FX We thank Xiu-fen Liu for providing primers for DPH1 and DPH5 genes. This
work was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research, and was funded in part 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.
NR 45
TC 29
Z9 30
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 1
PY 2012
VL 109
IS 18
BP 6898
EP 6903
DI 10.1073/pnas.1204523109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100034
PM 22509046
ER
PT J
AU Devaiah, BN
Lewis, BA
Cherman, N
Hewitt, MC
Albrecht, BK
Robey, PG
Ozato, K
Sims, RJ
Singer, DS
AF Devaiah, Ballachanda N.
Lewis, Brian A.
Cherman, Natasha
Hewitt, Michael C.
Albrecht, Brian K.
Robey, Pamela G.
Ozato, Keiko
Sims, Robert J., III
Singer, Dinah S.
TI BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA
Polymerase II carboxy-terminal domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; P-TEFB; TRANSCRIPTION; ELONGATION;
PROGRESSION; INTERACTS; CYCLE; REPLICATION; RECRUITMENT; INHIBITION
AB The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt's lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.
C1 [Devaiah, Ballachanda N.; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Lewis, Brian A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Cherman, Natasha; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Ozato, Keiko] Natl Inst Dent & Craniofacial Res, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
[Hewitt, Michael C.; Albrecht, Brian K.; Sims, Robert J., III] Constellat Pharmaceut Inc, Cambridge, MA 02142 USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM dinah.singer@nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Drs. Andrew Stern, Kent Hunter, and Lou Staudt for critical
reading of the manuscript and members of the laboratory for discussions.
We also thank Dr. Anne Gegonne for help with the 5-flourouridine cell
staining. This research was supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research.
NR 37
TC 102
Z9 104
U1 2
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 MAY 1
PY 2012
VL 109
IS 18
BP 6927
EP 6932
DI 10.1073/pnas.1120422109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100039
PM 22509028
ER
PT J
AU Yang, CZ
Iyer, RR
Yu, ACH
Yong, RL
Park, DM
Weil, RJ
Ikejiri, B
Brady, RO
Lonser, RR
Zhuang, ZP
AF Yang, Chunzhang
Iyer, Rajiv R.
Yu, Albert C. H.
Yong, Raymund L.
Park, Deric M.
Weil, Robert J.
Ikejiri, Barbara
Brady, Roscoe O.
Lonser, Russell R.
Zhuang, Zhengping
TI beta-Catenin signaling initiates the activation of astrocytes and its
dysregulation contributes to the pathogenesis of astrocytomas
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE astrocyte activation; glioblastoma multiforme; wound healing; adherent
junction
ID CONTACT INHIBITION; CELL-MIGRATION; STEM-CELLS; IN-VITRO; EXPRESSION;
PATHWAY; DISEASE; GROWTH; CADHERIN; PROTEIN
AB Astrocytes are the most abundant cell of the CNS and demonstrate contact inhibition in which a nonproliferative, nonmotile cellular state is achieved once stable intercellular contacts are formed between mature cells. Cellular injury disrupts these intercellular contacts, causing a loss of contact inhibition and the rapid initiation of healing. Dysregulation of the molecular pathways involved in this process is thought to lead to an aggressive cellular state associated with neoplasia. We investigated whether a comparable correlation exists between the response of astrocytes to injury and the malignant phenotype of astrocytomas. We discovered that the loss of contact inhibition plays a critical role in the initiation and regulation of reactive astrocytes in the healing of wounds. In particular, injury of the astrocytes interrupts and destabilizes the cadherin-catenin complexes at the cell membrane leading to nuclear translocation of beta-catenin and characteristic changes associated with the activation of astrocytes. Similar signaling pathways are found to be active-but dysregulated-in astrocytomas. Inhibition of beta-catenin signaling diminished both the response of astrocytes to injury and induction of the malignant phenotype of astrocytomas. The findings shed light on a unique mechanism associated with the pathogenesis of astrocytomas and provide a model for the loss of contact inhibition that may broadly apply to understanding the mechanisms of tissue repair and tumorigenesis in the brain.
C1 [Yang, Chunzhang; Iyer, Rajiv R.; Yong, Raymund L.; Ikejiri, Barbara; Brady, Roscoe O.; Lonser, Russell R.; Zhuang, Zhengping] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Yu, Albert C. H.] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci,Minist Educ,Neurosci Res Inst, Dept Neurobiol,Minist Publ Hlth,Key Lab Neurosci, Beijing 100191, Peoples R China.
[Park, Deric M.] Univ Virginia, Hlth Sci Ctr, Dept Neurol Surg, Charlottesville, VA 22903 USA.
[Weil, Robert J.] Cleveland Clin, Neurol Inst, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Dept Neurosurg, Cleveland, OH 44195 USA.
RP Brady, RO (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM bradyr@ninds.nih.gov; lonserr@ninds.nih.gov; zhuangp@ninds.nih.gov
RI Park, Deric/C-5675-2013
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health; Melvin Burkhardt chair in neurosurgical oncology;
Karen Colina Wilson research endowment within the Brain Tumor and
Neuro-Oncology Center at the Cleveland Clinic Foundation
FX We thank Dr. Dragan Maric for the assistance in flowcytometry assay and
data analysis. This research was supported by the intramural research
program in the National Institute of Neurological Disorders and Stroke
at the National Institutes of Health; and by the Melvin Burkhardt chair
in neurosurgical oncology and the Karen Colina Wilson research endowment
within the Brain Tumor and Neuro-Oncology Center at the Cleveland Clinic
Foundation.
NR 39
TC 29
Z9 31
U1 1
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 1
PY 2012
VL 109
IS 18
BP 6963
EP 6968
DI 10.1073/pnas.1118754109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100045
PM 22505738
ER
PT J
AU Dolan, BP
Sharma, AA
Gibbs, JS
Cunningham, TJ
Bennink, JR
Yewdell, JW
AF Dolan, Brian P.
Sharma, Aditi A.
Gibbs, James S.
Cunningham, Tshaka J.
Bennink, Jack R.
Yewdell, Jonathan W.
TI MHC class I antigen processing distinguishes endogenous antigens based
on their translation from cellular vs. viral mRNA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID PROTEIN-SYNTHESIS; CYTOSOLIC PEPTIDES; CELLS; DEGRADATION; EXPRESSION;
IMMUNODOMINANCE; TRANSCRIPTION; LOCALIZATION; GENERATION; ANTIBODIES
AB To better understand the generation of MHC class I-associated peptides, we used a model antigenic protein whose proteasome-mediated degradation is rapidly and reversibly controlled by Shield-1, a cell-permeant drug. When expressed from a stably transfected gene, the efficiency of antigen presentation is similar to 2%, that is, one cell-surface MHC class I-peptide complex is generated for every 50 folded source proteins degraded upon Shield-1 withdrawal. By contrast, when the same protein is expressed by vaccinia virus, its antigen presentation efficiency is reduced similar to 10-fold to values similar to those reported for other vaccinia virus-encoded model antigens. Virus infection per se does not modify the efficiency of antigen processing. Rather, the efficiency difference between cellular and virus-encoded antigens is based on whether the antigen is synthesized from transgene- vs. virus-encoded mRNA. Thus, class I antigen-processing machinery can distinguish folded proteins based on the precise details of their synthesis to modulate antigen presentation efficiency.
C1 [Dolan, Brian P.; Sharma, Aditi A.; Gibbs, James S.; Cunningham, Tshaka J.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
FU Intramural NIH HHS
NR 32
TC 18
Z9 19
U1 0
U2 0
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 MAY 1
PY 2012
VL 109
IS 18
BP 7025
EP 7030
DI 10.1073/pnas.1112387109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100056
PM 22509014
ER
PT J
AU Schulze, K
Vargha-Khadem, F
Mishkin, M
AF Schulze, Katrin
Vargha-Khadem, Faraneh
Mishkin, Mortimer
TI Test of a motor theory of long-term auditory memory
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE evolution; mimic; arcuate fasciculus
ID SUPERIOR TEMPORAL SULCUS; SPEECH-PERCEPTION; RECOGNITION MEMORY; HUMAN
BRAIN; DEVELOPMENTAL AMNESIA; LANGUAGE PATHWAYS; PREMOTOR CORTEX; MIRROR
NEURONS; RHESUS-MONKEY; BROCAS AREA
AB Monkeys can easily form lasting central representations of visual and tactile stimuli, yet they seem unable to do the same with sounds. Humans, by contrast, are highly proficient in auditory long-term memory (LTM). These mnemonic differences within and between species raise the question of whether the human ability is supported in some way by speech and language, e. g., through subvocal reproduction of speech sounds and by covert verbal labeling of environmental stimuli. If so, the explanation could be that storing rapidly fluctuating acoustic signals requires assistance from the motor system, which is uniquely organized to chain-link rapid sequences. To test this hypothesis, we compared the ability of normal participants to recognize lists of stimuli that can be easily reproduced, labeled, or both (pseudowords, nonverbal sounds, and words, respectively) versus their ability to recognize a list of stimuli that can be reproduced or labeled only with great difficulty (reversed words, i.e., words played backward). Recognition scores after 5-min delays filled with articulatory-suppression tasks were relatively high (75-80% correct) for all sound types except reversed words; the latter yielded scores that were not far above chance (58% correct), even though these stimuli were discriminated nearly perfectly when presented as reversed-word pairs at short intrapair intervals. The combined results provide preliminary support for the hypothesis that participation of the oromotor system may be essential for laying down the memory of speech sounds and, indeed, that speech and auditory memory may be so critically dependent on each other that they had to coevolve.
C1 [Mishkin, Mortimer] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
[Schulze, Katrin; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, London WC1N 1EH, England.
RP Mishkin, M (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA.
EM mishkinm@mail.nih.gov
RI Schulze, Katrin/A-7385-2010
FU National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services; Medical Research Council
[G0300117/65439]; University College London [06CN05]
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services, as well as by the Medical
Research Council (G0300117/65439) and University College London Pump
Prime Grant 06CN05.
NR 63
TC 14
Z9 14
U1 1
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 1
PY 2012
VL 109
IS 18
BP 7121
EP 7125
DI 10.1073/pnas.1204717109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100072
PM 22511719
ER
PT J
AU Li, YP
Ramirez, S
Gottwein, JM
Scheel, TKH
Mikkelsen, L
Purcell, RH
Bukh, J
AF Li, Yi-Ping
Ramirez, Santseharay
Gottwein, Judith M.
Scheel, Troels K. H.
Mikkelsen, Lotte
Purcell, Robert H.
Bukh, Jens
TI Robust full-length hepatitis C virus genotype 2a and 2b infectious
cultures using mutations identified by a systematic approach applicable
to patient strains
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE RNA; neutralization; inhibitor; interferon; antiviral
ID CELL-CULTURE; IN-VITRO; GENETIC-VARIATION; HUH-7 CELLS; CDNA-CLONE;
REPLICATION; RNA; INHIBITOR; PROTEIN; POTENT
AB Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, and to date only the JFH1 (genotype 2a) recombinant replicates spontaneously in hepatoma cells and releases infectious virus. A JFH1 chimera with the 5' end through NS2 from another genotype 2a strain, J6, had enhanced infectivity. However, the full-length J6 clone (J6CF), which we previously found to be fully functional in vivo, was replication incompetent in vitro. Through a systematic approach of culturing J6 with minimal JFH1 sequences, we identified three mutations in NS3, NS4A, and NS5B that permitted full-length J6 propagation and adaptation with infectivity titers comparable to JFH1-based systems. The most efficient recombinant, J6cc, had six adaptive mutations and did not accumulate additional changes following viral passage. We demonstrated that HCV NS3/NS4A protease-, NS5A- and NS5B polymerase-directed drugs respectively inhibited full-length J6 infection dose dependently. Importantly, the three J6-derived mutations enabled culture adaptation of the genetically divergent isolate J8 (genotype 2b), which differed from the J6 nucleotide sequence by 24%. The most efficient recombinant, J8cc, had nine adaptive mutations and was genetically stable after viral passage. The availability of these robust JFH1-independent genotype 2a and 2b culture systems represents an important advance, and the approach used might permit culture development of other isolates, with implications for improved individualized treatments of HCV patients and for development of broadly efficient vaccines.
C1 [Purcell, Robert H.; Bukh, Jens] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M.; Scheel, Troels K. H.; Mikkelsen, Lotte; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, DK-2650 Hvidovre, Denmark.
[Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M.; Scheel, Troels K. H.; Mikkelsen, Lotte; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M.; Scheel, Troels K. H.; Mikkelsen, Lotte; Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen N, Denmark.
RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM RPURCELL@niaid.nih.gov; jbukh@sund.ku.dk
RI Ramirez, Santseharay/R-9257-2016;
OI Ramirez, Santseharay/0000-0003-3699-1814; Scheel,
Troels/0000-0003-1545-4067
FU Lundbeck Foundation; Danish Cancer Society; Novo Nordisk Foundation; A.
P. Moller og Hustru Chastine Mc-Kinney Mollers Fondation; Danish Council
for Independent Research - Medical Sciences; National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX We thank L. Ghanem, A. L. Sorensen, and B. Landt for technical
assistance; S. B. Serre and T. Carlsen for discussions; and J. O.
Nielsen and O. Andersen for providing valuable support (all from
Copenhagen University Hospital). We thank S. U. Emerson (National
Institutes of Health, Bethesda, MD), C. M. Rice (Rockefeller University)
and T. Wakita (National Institute of Infectious Diseases, Tokyo, Japan)
for providing reagents. This study was supported by research grants from
Lundbeck Foundation (to J. G. M., T. H. K. S., and J. B.); The Danish
Cancer Society (to J. M. G. and J. B.); The Novo Nordisk Foundation (to
J. M. G. and J. B.); The A. P. Moller og Hustru Chastine Mc-Kinney
Mollers Fondation (to J. B.); the Danish Council for Independent
Research - Medical Sciences (to Y.-P.L., S. R., and J. B.); and in part
by the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health (to R. H. P. and
J. B.). S. R. and T. K. H. S. are the recipients of Individual
Postdoctoral Stipends from the Danish Council for Independent Research -
Medical Sciences.
NR 67
TC 36
Z9 38
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 1
PY 2012
VL 109
IS 18
BP E1101
EP E1110
DI 10.1073/pnas.1203829109
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 936PI
UT WOS:000303602100011
PM 22467829
ER
PT J
AU Pellett, PE
Ablashi, DV
Ambros, PF
Agut, H
Caserta, MT
Descamps, V
Flamand, L
Gautheret-Dejean, A
Hall, CB
Kamble, RT
Kuehl, U
Lassner, D
Lautenschlager, I
Loomis, KS
Luppi, M
Lusso, P
Medveczky, PG
Montoya, JG
Mori, Y
Ogata, M
Pritchett, JC
Rogez, S
Seto, E
Ward, KN
Yoshikawa, T
Razonable, RR
AF Pellett, Philip E.
Ablashi, Dharam V.
Ambros, Peter F.
Agut, Henri
Caserta, Mary T.
Descamps, Vincent
Flamand, Louis
Gautheret-Dejean, Agnes
Hall, Caroline B.
Kamble, Rammurti T.
Kuehl, Uwe
Lassner, Dirk
Lautenschlager, Irmeli
Loomis, Kristin S.
Luppi, Mario
Lusso, Paolo
Medveczky, Peter G.
Montoya, Jose G.
Mori, Yasuko
Ogata, Masao
Pritchett, Joshua C.
Rogez, Sylvie
Seto, Edward
Ward, Katherine N.
Yoshikawa, Tetsushi
Razonable, Raymund R.
TI Chromosomally integrated human herpesvirus 6: questions and answers
SO REVIEWS IN MEDICAL VIROLOGY
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION;
POLYMERASE-CHAIN-REACTION; REPLICATION IN-VITRO; MAREKS-DISEASE VIRUS;
HHV-6 DNA; HUMAN-HERPESVIRUS-6 REACTIVATION; LIVER-TRANSPLANT; VIRAL
LOAD; HYPERSENSITIVITY-SYNDROME
AB Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Pellett, Philip E.] Wayne State Univ, Dept Immunol & Microbiol, Sch Med, Detroit, MI 48201 USA.
[Ablashi, Dharam V.; Loomis, Kristin S.; Pritchett, Joshua C.] HHV 6 Fdn, Santa Barbara, CA USA.
[Ambros, Peter F.] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria.
[Agut, Henri; Gautheret-Dejean, Agnes] Grp Hosp Pitie Salpetriere, Serv Virol, F-75634 Paris, France.
[Caserta, Mary T.] Univ Rochester, Sch Med, Dept Pediat, Rochester, NY 14642 USA.
[Descamps, Vincent] Bichat Claude Bernard Hosp, Dept Dermatol, Paris, France.
[Flamand, Louis] Univ Laval, Rheumatol & Immunol Res Ctr, Quebec City, PQ, Canada.
[Hall, Caroline B.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Hall, Caroline B.] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA.
[Kamble, Rammurti T.] Baylor Coll Med, Houston, TX 77030 USA.
[Kuehl, Uwe] Charite, Berlin, Germany.
[Lassner, Dirk] Inst Cardiac Diag & Treatment, Berlin, Germany.
[Lautenschlager, Irmeli] HUSLAB, Dept Virol, Helsinki, Finland.
[Lautenschlager, Irmeli] Univ Helsinki, Helsinki, Finland.
[Luppi, Mario] Univ Modena & Reggio Emilia, Emilia Romagna, Italy.
[Lusso, Paolo] NIAID, NIH, Bethesda, MD 20892 USA.
[Medveczky, Peter G.] Univ S Florida, Dept Mol Med, Tampa, FL USA.
[Montoya, Jose G.] Stanford Univ, Dept Infect Dis, Stanford, CA 94305 USA.
[Mori, Yasuko] Kobe Univ, Div Clin Virol, Kobe, Hyogo 657, Japan.
[Ogata, Masao] Oita Univ, Ctr Blood Transfus, Oita 87011, Japan.
[Rogez, Sylvie] CHRU Dupuytren, Dept Virol, Limoges, France.
[Seto, Edward] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL USA.
[Ward, Katherine N.] UCL, Dept Infect, London, England.
[Yoshikawa, Tetsushi] Fujita Hlth Univ, Dept Pediat, Toyoake, Aichi, Japan.
[Razonable, Raymund R.] Mayo Clin, Div Infect Dis, Rochester, MN 55905 USA.
RP Pellett, PE (reprint author), Wayne State Univ, Dept Immunol & Microbiol, Sch Med, 6225 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA.
EM ppellett@med.wayne.edu; razonable.raymund@mayo.edu
RI Medveczky, Peter/A-6846-2012; Luppi, Mario/J-3668-2016; Rogez,
Sylvie/O-8891-2016;
OI Luppi, Mario/0000-0002-0373-1154; Rogez, Sylvie/0000-0002-4092-7164;
Medveczky, Peter/0000-0002-1798-2595; Ogata, Masao/0000-0002-4896-5878;
Lassner, Dirk/0000-0003-0815-7013; Ambros, Peter F./0000-0002-5507-7211
FU HHV-6 Foundation
FX This project was supported by the HHV-6 Foundation. Several of the
co-authors have received research grants from the HHV-6 Foundation.
NR 88
TC 84
Z9 85
U1 1
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1052-9276
J9 REV MED VIROL
JI Rev. Med. Virol.
PD MAY
PY 2012
VL 22
IS 3
BP 144
EP 155
DI 10.1002/rmv.715
PG 12
WC Virology
SC Virology
GA 930EH
UT WOS:000303119600002
PM 22052666
ER
PT J
AU Kelly, DL
Raley, HG
Lo, S
Wright, K
Liu, F
McMahon, RP
Moolchan, ET
Feldman, S
Richardson, CM
Wehring, HJ
Heishman, SJ
AF Kelly, Deanna L.
Raley, Heather G.
Lo, Suzanne
Wright, Katherine
Liu, Fang
McMahon, Robert P.
Moolchan, Eric T.
Feldman, Stephanie
Richardson, Charles M.
Wehring, Heidi J.
Heishman, Stephen J.
TI Perception of Smoking Risks and Motivation to Quit Among
Nontreatment-Seeking Smokers With and Without Schizophrenia
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE smoking; schizophrenia; motivation; health risks
ID FAGERSTROM TOLERANCE QUESTIONNAIRE; CIGARETTE-SMOKING; MONETARY
REINFORCEMENT; TRANSDERMAL NICOTINE; EXTRINSIC MOTIVATION; PSYCHOTIC
DISORDER; CESSATION; OUTPATIENTS; REHABILITATION; DEPENDENCE
AB We examined perceived consequences/benefits of cigarette smoking and motivation for quitting in nontreatment-seeking smokers who had schizophrenia or schizoaffective disorder (N = 100) or had no Axis I psychiatric disorder (normals, N = 100).
Participants completed questionnaires and provided a breath carbon monoxide (CO) sample 10-15 minutes after smoking 1 preferred-brand cigarette. Primary assessments included the Smoking Consequences Questionnaire-Adult, the Reasons for Quitting Scale, and the Stages of Change.
There were no differences between the schizophrenia and control group in mean age of smoking onset (16.2 +/- 5.4 vs 15.6 +/- 5.5 y, P = .44), number of cigarettes daily (17.9 +/- 11.6 vs 17.0 +/- 7.9, P = 0.51), or in breath CO (28.0 +/- 14.5 vs 22.9 +/- 8.0 ppm, P = .61). Compared with normals, people with schizophrenia report greater stimulation/state enhancement (P < .0001) and social facilitation (P < .004) from smoking. People with schizophrenia had less appreciation of health risks associated with smoking than normal controls (P < .0001) and were less motivated to quit smoking than normal controls (P = .002), even though they were as likely to be in the preparation stage of change. Immediate reinforcement (P = .04) and health concerns (P = .002) were rated lower as motivators for considering quitting smoking in schizophrenia than normals. People with schizophrenia reported greater motivation to stop smoking due to social pressure/rewards than normals (P = .047).
This study underscores the degree to which people with schizophrenia perceive the state-enhancing effects of smoking and their lower appreciation for health risks of smoking compared with normal controls.
C1 [Kelly, Deanna L.; Raley, Heather G.; Wright, Katherine; Liu, Fang; McMahon, Robert P.; Feldman, Stephanie; Richardson, Charles M.; Wehring, Heidi J.] Univ Maryland, Baltimore Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
[Lo, Suzanne; Heishman, Stephen J.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
[Moolchan, Eric T.] Alkermes Inc, Cambridge, MA USA.
RP Kelly, DL (reprint author), Univ Maryland, Baltimore Sch Med, Maryland Psychiat Res Ctr, Box 21247, Baltimore, MD 21228 USA.
EM dkelly@mprc.umaryland.edu
RI McMahon, Robert/C-5462-2009
FU National Institutes of Health, National Institute on Drug Abuse;
National Institute on Drug Abuse Residential Research Support Services
[HHSN271200599091CADB, NO-1DA-5-9909]
FX Intramural Research Program of the National Institutes of Health,
National Institute on Drug Abuse, and National Institute on Drug Abuse
Residential Research Support Services Contract HHSN271200599091CADB,
NO-1DA-5-9909 (PI: Deanna L. Kelly).
NR 44
TC 17
Z9 17
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAY
PY 2012
VL 38
IS 3
BP 543
EP 551
DI 10.1093/schbul/sbq124
PG 9
WC Psychiatry
SC Psychiatry
GA 930VB
UT WOS:000303169000022
PM 21041835
ER
PT J
AU Knutson, KL
Zhao, XC
Mattingly, M
Galli, G
Cizza, G
AF Knutson, Kristen L.
Zhao, Xiongce
Mattingly, Megan
Galli, Giulia
Cizza, Giovanni
TI Predictors of sleep-disordered breathing in obese adults who are chronic
short sleepers
SO SLEEP MEDICINE
LA English
DT Article
DE Sleep-disordered breathing; Obese; Actigraphy; Subjective sleep quality;
Sleepiness; Apnea
ID MIDDLE-AGED ADULTS; CARDIOVASCULAR-DISEASE; DAYTIME SLEEPINESS; HEART
HEALTH; RISK-FACTOR; APNEA; PREVALENCE; INDEX; DURATION; STROKE
AB Background: Sleep disordered breathing (SDB) is common in obese adults, but not all obese adults have SDB. The aim of these analyses was to determine what predicted SDB in a sample of obese adults.
Methods: We conducted cross-sectional analysis of 139 obese men and women aged 18-50 years who are chronic short sleepers. Habitual sleep duration and sleep efficiency were estimated using two weeks of wrist actigraphy. Respiratory disturbance index (RDI) was assessed by a portable screening device. SDB was defined as RDI >= 15 events h (1). Subjective sleep quality, sleepiness, and sociodemographic characteristics were evaluated by questionnaires.
Results: Increased sleep duration from actigraphy was associated with reduced odds of SDB (OR 0.44 per hour, p = 0.043). Neither subjective sleep quality nor sleepiness was associated with SDB. Male sex, older age, and increased waist circumference were associated with increased odds of SDB.
Conclusions: In this sample of obese adults, subjective measures of sleep quality and sleepiness were not indicators of SDB. These results suggest that, in obese patients, physicians should not rely on subjective measures to determine who should be referred for a clinical sleep study. A wider use of portable apnea screening devices should be considered in nonsymptomatic, non-Hispanic white males. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Knutson, Kristen L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Zhao, Xiongce; Mattingly, Megan; Galli, Giulia; Cizza, Giovanni] NIDDK, Sect Neuroendocrinol Obes, Bethesda, MD USA.
[Galli, Giulia] Univ Hosp Pisa, Dept Endocrinol & Kidney, Pisa, Italy.
RP Knutson, KL (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave,MC6076, Chicago, IL 60637 USA.
EM kknutson@medicine.bsd.uchicago.edu; Zhao.Xiongce@nih.gov;
mattinglym@niddk.nih.gov; giulia.galli@nih.gov;
cizzag@intra.niddk.nih.gov
OI Knutson, Kristen/0000-0002-2751-6168
FU National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK);
Clinical Center, National Institutes of Health (NIH)
FX This study is supported by the Intramural Program of the National
Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) and the
Clinical Center, National Institutes of Health (NIH). This study is
conducted under the NIDDK protocol 06-DK-0036 and is listed in
ClinicalTrials.gov (identifier: NCT00261898). Statistical expertise and
a central sample handling and assays facility are provided by the NIDDK
Intramural Obesity Initiative of the NIH Clinical Center.
NR 27
TC 6
Z9 6
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
J9 SLEEP MED
JI Sleep Med.
PD MAY
PY 2012
VL 13
IS 5
BP 484
EP 489
DI 10.1016/j.sleep.2011.11.009
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 933FX
UT WOS:000303346800006
PM 22326831
ER
PT J
AU Sappol, M
AF Sappol, Michael
TI Anatomy as Spectacle: Public Exhibitions of the Body from 1700 to the
Present
SO SOCIAL HISTORY OF MEDICINE
LA English
DT Book Review
C1 [Sappol, Michael] Natl Lib Med, Bethesda, MD 20894 USA.
RP Sappol, M (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.
EM sappolm@mail.nlm.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0951-631X
J9 SOC HIST MED
JI Soc. Hist. Med.
PD MAY
PY 2012
VL 25
IS 2
BP 546
EP 548
DI 10.1093/shm/hks017
PG 3
WC History; History & Philosophy Of Science
SC History; History & Philosophy of Science
GA 933BK
UT WOS:000303334000020
ER
PT J
AU Chen, XJ
Summers, RM
Cho, M
Bagci, U
Yao, JY
AF Chen, Xinjian
Summers, Ronald M.
Cho, Monique
Bagci, Ulas
Yao, Jianhua
TI An Automatic Method for Renal Cortex Segmentation on CT Images:
Evaluation on Kidney Donors
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Kidney; renal cortex; automatic renal cortex segmentation; kidney donors
ID ENHANCED MR-ANGIOGRAPHY; SEMIAUTOMATED SEGMENTATION; GRAPH-CUTS;
ALGORITHMS; RENOGRAPHY; EXPERIENCE; AGREEMENT; MODELS
AB Rationale and Objectives: The aims of this study were to develop and validate an automated method to segment the renal cortex on contrast-enhanced abdominal computed tomographic images from kidney donors and to track cortex volume change after donation.
Materials and Methods: A three-dimensional fully automated renal cortex segmentation method was developed and validated on 37 arterial phase computed tomographic data sets (27 patients, 10 of whom underwent two computed tomographic scans before and after nephrectomy) using leave-one-out strategy. Two expert interpreters manually segmented the cortex slice by slice, and linear regression analysis and Bland-Altman plots were used to compare automated and manual segmentation. The true-positive and false-positive volume fractions were also calculated to evaluate the accuracy of the proposed method. Cortex volume changes in 10 subjects were also calculated.
Results: The linear regression analysis results showed that the automated and manual segmentation methods had strong correlations, with Pearson's correlations of 0.9529, 0.9309, 0.9283, and 0.9124 between intraobserver variation, interobserver variation, automated and user 1, and automated and user 2, respectively (P < .001 for all analyses). The Bland-Altman plots for cortex segmentation also showed that the automated and manual methods had agreeable segmentation. The mean volume increase of the cortex for the 10 subjects was 35.1 +/- 13.2% (P < .01 by paired t test). The overall true-positive and false-positive volume fractions for cortex segmentation were 90.15 +/- 3.11% and 0.85 +/- 0.05%. With the proposed automated method, the time for cortex segmentation was reduced from 20 minutes for manual segmentation to 2 minutes.
Conclusions: The proposed method was accurate and efficient and can replace the current subjective and time-consuming manual procedure. The computer measurement confirms the volume of renal cortex increases after kidney donation.
C1 [Chen, Xinjian; Summers, Ronald M.; Bagci, Ulas; Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Cho, Monique] NIDDK, Kidney Dis Branch, Bethesda, MD USA.
RP Yao, JY (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10,Room 1C515, Bethesda, MD 20892 USA.
EM jyao@cc.nih.gov
RI Bagci, Ulas/A-4225-2012; Chen, Xinjian/E-8592-2016;
OI Bagci, Ulas/0000-0001-7379-6829
FU National Institutes of Health Clinical Center
FX From the Radiology and Imaging Sciences Department, National Institutes
of Health Clinical Center, Building 10, Room 10515, Bethesda, MD
20892-1182 (X.C., R.M.S., U.B., J.Y.); and the Kidney Disease Branch,
National Institute of Diabetes and Digestive and Kidney Diseases,
Bethesda, Maryland (M.C.). Received September 26, 2011; accepted January
9, 2012. This paper was presented at the 2010 annual meeting of the
Radiological Society of North America as a scientific paper. This
research was supported by the Intramural Program of the National
Institutes of Health Clinical Center. Address correspondence to: J.Y.
e-mail: jyao@cc.nih.gov
NR 28
TC 8
Z9 9
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD MAY
PY 2012
VL 19
IS 5
BP 562
EP 570
DI 10.1016/j.acra.2012.01.005
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 929OR
UT WOS:000303075700009
PM 22341876
ER
PT J
AU Linguraru, MG
Sandberg, JK
Jones, EC
Petrick, N
Summers, RM
AF Linguraru, Marius George
Sandberg, Jesse K.
Jones, Elizabeth C.
Petrick, Nicholas
Summers, Ronald M.
TI Assessing Hepatomegaly: Automated Volumetric Analysis of the Liver
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Hepatomegaly; volumetric analysis; liver; segmentation; nomogram
ID SURGICAL DECISION-MAKING; MULTIDETECTOR ROW CT; COMPUTED-TOMOGRAPHY;
RIEDELS LOBE; ULTRASONIC DETERMINATION; OBSERVER VARIATION; SPLEEN
VOLUME; LIVING DONOR; SPIRAL CT; SIZE
AB Rationale and Objectives: The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly.
Materials and Methods: Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated.
Results: The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences (P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 +/- 0.25 and 2.32 +/- 0.75 L, respectively. One-way analysis of variance found that body surface area (P = .004) and gender (P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables (P > .18). H-score cutoffs of 0.92 and 1.08 L/m(2) were used to define mild and massive hepatomegaly (95% confidence interval, +/- 0.02 L/m(2)). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98.
Conclusions: Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.
C1 [Linguraru, Marius George; Sandberg, Jesse K.; Jones, Elizabeth C.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM mlingura@cnmc.org
FU National Institutes of Health, Clinical Center; US Food and Drug
Administration
FX From the Imaging Biomarkers and Computer-Aided Diagnosis Laboratory,
Radiology and Imaging Sciences, Clinical Center, National Institutes of
Health, Bethesda, Maryland (M.G.L., J.K.S., E.C.J., R.M.S.); The Sheikh
Zayed Institute for Pediatric Surgical Innovation, Children's National
Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010 (M.G.L.);
and the Center for Devices and Radiological Health, US Food and Drug
Administration, Silver Spring, Maryland (N.P.). Received September 26,
2011; accepted January 28, 2012. This work was supported in part by the
Intramural Research Programs of the National Institutes of Health,
Clinical Center, and the US Food and Drug Administration. The mention of
commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either actual or
implied endorsements of such products by the US Department of Health and
Human Services. Address correspondence to: M.G.L. e-mail:
mlingura@cnmc.org
NR 58
TC 8
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD MAY
PY 2012
VL 19
IS 5
BP 588
EP 598
DI 10.1016/j.acra.2012.01.015
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 929OR
UT WOS:000303075700012
PM 22361033
ER
PT J
AU Garces, A
Mcclure, EM
Hambidge, M
Krebs, NF
Mazariegos, M
Wright, LL
Moore, J
Carlo, WA
AF Garces, Ana
Mcclure, Elizabeth M.
Hambidge, Michael
Krebs, Nancy F.
Mazariegos, Manolo
Wright, Linda L.
Moore, Janet
Carlo, Waldemar A.
TI Training traditional birth attendants on the WHO Essential Newborn Care
reduces perinatal mortality
SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
LA English
DT Article
DE Developing countries; newborn care; perinatal mortality; stillbirths;
traditional birth attendants
ID NEONATAL DEATHS; STILLBIRTHS; COUNTRIES
AB Objectives. To evaluate the impact of birth attendant training using the World Health Organization Essential Newborn Care (ENC) course among traditional birth attendants, with a particular emphasis on the effect of acquisition of skills on perinatal outcomes. Design. Population-based, prospective, interventional pre-post design study. Setting. 11 rural clusters in Chimaltenango, Guatemala. Population. Health care providers. Methods. This study analyzed the effect of training and implementation of the ENC health care provider training course between September 2005 and December 2006. Outcome measures. The primary outcome measure was the rate of death from all causes in the first seven days after birth in fetuses/infants =1500g. Secondary outcome measures were overall rate of stillbirth, rate of perinatal death, which included stillbirths plus neonatal deaths in the first seven days in fetuses/infants =1500g. Results. Perinatal mortality decreased from 39.5/1000 pre-ENC to 26.4 post-ENC (RR 0.72; 95%CI 0.540.97). This reduction was attributable almost entirely to a decrease in the stillbirth rate of 21.4/1000 pre-Essential Newborn Care to 7.9/1000 post-ENC (RR 0.40; 95%CI 0.250.64). Seven-day neonatal mortality did not decrease (18.3/1000 to 18.6/1000; RR 1.05; 95%CI 0.701.57). Conclusion. Essential Newborn Care training reduced stillbirths in a population-based controlled study with deliveries conducted almost exclusively by traditional birth attendants. Scale-up of this intervention in other settings might help assess reproducibility and sustainability.
C1 [Garces, Ana; Mazariegos, Manolo] IMSALUD, Guatemala City, Guatemala.
[Mcclure, Elizabeth M.; Moore, Janet] RTI, Res Triangle Pk, NC USA.
[Hambidge, Michael; Krebs, Nancy F.] Univ Colorado Denver, Aurora, CO USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
[Carlo, Waldemar A.] Univ Alabama, Birmingham, AL USA.
RP Garces, A (reprint author), IMSALUD, 3Ra Calle A 6-56,Zona 10, Guatemala City, Guatemala.
EM anagarces@imsalud.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development) [NICHD U01 HD040657 UCD, U01 HD043464 UAB, U01 HD040636
RTI]
FX This study was funded by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD U01 HD040657 UCD; U01
HD043464 UAB; and U01 HD040636 RTI).
NR 12
TC 4
Z9 4
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-6349
J9 ACTA OBSTET GYN SCAN
JI Acta Obstet. Gynecol. Scand.
PD MAY
PY 2012
VL 91
IS 5
BP 593
EP 597
DI 10.1111/j.1600-0412.2012.01374.x
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 928RR
UT WOS:000303001500012
PM 22324644
ER
PT J
AU Litten, RZ
Egli, M
Heilig, M
Cui, CH
Fertig, JB
Ryan, ML
Falk, DE
Moss, H
Huebner, R
Noronha, A
AF Litten, Raye Z.
Egli, Mark
Heilig, Markus
Cui, Changhai
Fertig, Joanne B.
Ryan, Megan L.
Falk, Daniel E.
Moss, Howard
Huebner, Robert
Noronha, Antonio
TI Medications development to treat alcohol dependence: a vision for the
next decade
SO ADDICTION BIOLOGY
LA English
DT Review
DE Alcohol; alcohol dependence; alcohol use disorders; drug development;
medications
ID RANDOMIZED CONTROLLED-TRIAL; OPIOID RECEPTOR GENE; DOUBLE-BLIND; USE
DISORDERS; ETHANOL DRINKING; DRUG-DEPENDENCE; HEAVY-DRINKING;
UNITED-STATES; FUNCTIONAL POLYMORPHISM; ACHIEVING CONSILIENCE
AB More than 76 million people world-wide are estimated to have diagnosable alcohol use disorders (AUDs) (alcohol abuse or dependence), making these disorders a major global health problem. Pharmacotherapy offers promising means for treating AUDs, and significant progress has been made in the past 20 years. The US Food and Drug Administration approved three of the four medications for alcoholism in the last two decades. Unfortunately, these medications do not work for everyone, prompting the need for a personalized approach to optimize clinical benefit or more efficacious medications that can treat a wider range of patients, or both. To promote global health, the potential reorganization of the National Institutes of Health (NIH) must continue to support the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) vision of ensuring the development and delivery of new and more efficacious medications to treat AUDs in the coming decade. To achieve this objective, the NIAAA Medications Development Team has identified three fundamental long-range goals: (1) to make the drug development process more efficient; (2) to identify more efficacious medications, personalize treatment approaches, or both; and (3) to facilitate the implementation and adaptation of medications in real-world treatment settings. These goals will be carried out through seven key objectives. This paper describes those objectives in terms of rationale and strategy. Successful implementation of these objectives will result in the development of more efficacious and safe medications, provide a greater selection of therapy options and ultimately lessen the impact of this devastating disorder.
C1 [Litten, Raye Z.; Egli, Mark; Heilig, Markus; Cui, Changhai; Fertig, Joanne B.; Ryan, Megan L.; Falk, Daniel E.; Moss, Howard; Huebner, Robert; Noronha, Antonio] NIAAA, Bethesda, MD USA.
RP Litten, RZ (reprint author), NIAA, NIH, 5635 Fishers Lane,Room 2041, Rockville, MD 20852 USA.
EM rlitten@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
FU Intramural NIH HHS [Z99 AA999999]
NR 115
TC 78
Z9 81
U1 4
U2 19
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 MAY
PY 2012
VL 17
IS 3
BP 513
EP 527
DI 10.1111/j.1369-1600.2012.00454.x
PG 15
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 928QR
UT WOS:000302998400002
PM 22458728
ER
PT J
AU Schank, JR
Goldstein, AL
Rowe, KE
King, CE
Marusich, JA
Wiley, JL
Carroll, FI
Thorsell, A
Heilig, M
AF Schank, Jesse R.
Goldstein, Andrea L.
Rowe, Kelly E.
King, Courtney E.
Marusich, Julie A.
Wiley, Jenny L.
Carroll, F. Ivy
Thorsell, Annika
Heilig, Markus
TI The kappa opioid receptor antagonist JDTic attenuates alcohol seeking
and withdrawal anxiety
SO ADDICTION BIOLOGY
LA English
DT Article
DE Alcoholism; dynorphin; ethanol; reinstatement; self-administration;
stress
ID CORTICOTROPIN-RELEASING-FACTOR; N-TERMINAL KINASE; NOR-BINALTORPHIMINE;
COCAINE-SEEKING; PRIMING INJECTIONS; NUCLEUS-ACCUMBENS; AGONIST
U50,488H; ETHANOL INTAKE; DRUG-SEEKING; STRESS
AB The role of kappa-opioid receptors (KOR) in the regulation of alcohol-related behaviors is not completely understood. For example, alcohol consumption has been reported to increase following treatment with KOR antagonists in rats, but was decreased in mice with genetic deletion of KOR. Recent studies have further suggested that KOR antagonists may selectively decrease alcohol self-administration in rats following a history of dependence. We assessed the effects of the KOR antagonist JDTic on alcohol self-administration, reinstatement of alcohol seeking induced by alcohol-associated cues or stress, and acute alcohol withdrawal-induced anxiety (hangover anxiety). JDTic dose-dependently reversed hangover anxiety when given 48 hours prior to testing, a time interval corresponding to the previously demonstrated anxiolytic efficacy of this drug. In contrast, JDTic decreased alcohol self-administration and cue-induced reinstatement of alcohol seeking when administered 2 hours prior to testing, but not at longer pre-treatment times. For comparison, we determined that the prototypical KOR antagonist nor-binaltorphimine can suppress self-administration of alcohol at 2 hours pre-treatment time, mimicking our observations with JDTic. The effects of JDTic were behaviorally specific, as it had no effect on stress-induced reinstatement of alcohol seeking, self-administration of sucrose, or locomotor activity. Further, we demonstrate that at a 2 hours pre-treatment time JDTic antagonized the antinociceptive effects of the KOR agonist U50,488H but had no effect on morphine-induced behaviors. Our results provide additional evidence for the involvement of KOR in regulation of alcohol-related behaviors and provide support for KOR antagonists, including JDTic, to be evaluated as medications for alcoholism.
C1 [Schank, Jesse R.; Goldstein, Andrea L.; Rowe, Kelly E.; King, Courtney E.; Thorsell, Annika; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
[Marusich, Julie A.; Wiley, Jenny L.; Carroll, F. Ivy] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
RP Schank, JR (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,Bldg 10-CRC,Room 1-5330, Bethesda, MD 20892 USA.
EM jesse.schank@nih.gov
RI Shipper, Andrea/G-7407-2014;
OI Shipper, Andrea/0000-0003-2819-4276; Heilig, Markus/0000-0003-2706-2482;
Thorsell, Annika/0000-0003-3535-3845
FU National Institute on Alcohol Abuse and Alcoholism; National Institute
of Drug Abuse [DA09045]
FX The Authors would like to thank Dr. Andrea Cippitelli for methodological
advice. This research was funded by the National Institute on Alcohol
Abuse and Alcoholism Intramural Research Program and by National
Institute of Drug Abuse Grant #DA09045.
NR 59
TC 38
Z9 40
U1 1
U2 8
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 MAY
PY 2012
VL 17
IS 3
BP 634
EP 647
DI 10.1111/j.1369-1600.2012.00455.x
PG 14
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 928QR
UT WOS:000302998400013
PM 22515275
ER
PT J
AU Ghany, MG
Feld, JJ
Zhao, X
Heller, T
Doo, E
Rotman, Y
Nagabhyru, P
Koh, C
Kleiner, DE
Wright, EC
Liang, TJ
Hoofnagle, JH
AF Ghany, M. G.
Feld, J. J.
Zhao, X.
Heller, T.
Doo, E.
Rotman, Y.
Nagabhyru, P.
Koh, C.
Kleiner, D. E.
Wright, E. C.
Liang, T. J.
Hoofnagle, J. H.
TI Randomised clinical trial: the benefit of combination therapy with
adefovir and lamivudine for chronic hepatitis B
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID DIPIVOXIL; VIRUS; ENTECAVIR; RESISTANCE
AB Background
Combination antiviral therapy holds the promise of increasing response rates while decreasing antiviral resistance, but has yet to be shown to be beneficial or necessary in chronic hepatitis B.
Aim
To evaluate the benefit of combination therapy with adefovir and lamivudine versus adefovir alone in maintaining virological, biochemical and histological responses.
Methods
Patients with chronic hepatitis B with and without previous lamivudine therapy were randomised to receive adefovir alone (10 mg/daily) or adefovir and lamivudine (100 mg/daily) for up to 192 weeks. Study endpoints were (i) maintained virological (HBV DNA <500 copies/mL), biochemical and histological response, (ii) loss of HBeAg and (iii) loss of HBsAg.
Results
A total of 41 patients were enrolled, including 31 HBeAg -positive and 31 treatment-naive subjects. 30 patients remained on assigned therapy at 192 weeks. The percentage of patients achieving a combined maintained response was higher in the combination than the monotherapy arm, both at week 48 (59% vs. 26%, P = 0.06) and 192 (68% vs. 31%, P = 0.03). At week 192, 76% of the combination vs. 36% of the monotherapy group had loss of HBeAg (P = 0.03). One patient receiving adefovir cleared HBsAg. Adefovir resistance developed in 6 of 19 (32%) monotherapy but none of 22 combination treated patients (P = 0.03).
Conclusions
Extended combination therapy with lamivudine and adefovir is associated with a high rate of long-term virological and biochemical response. Adefovir monotherapy appears to be less effective mainly because of poor initial response and the ultimate development of antiviral resistance (Clinical. Trials.gov NCT00023309).
C1 [Ghany, M. G.; Feld, J. J.; Heller, T.; Doo, E.; Rotman, Y.; Nagabhyru, P.; Koh, C.; Liang, T. J.; Hoofnagle, J. H.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kleiner, D. E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Zhao, X.; Wright, E. C.] NIDDKD, Off Director, NIH, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), NIDDKD, Liver Dis Branch, NIH, Bldg 10,Room 9B 16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Cancer Institute, 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 Cancer Institute, National Institutes of Health.
NR 23
TC 13
Z9 14
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD MAY
PY 2012
VL 35
IS 9
BP 1027
EP 1035
DI 10.1111/j.1365-2036.2012.05059.x
PG 9
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 927HP
UT WOS:000302898400005
PM 22449251
ER
PT J
AU Mannelli, P
Peindl, K
Wu, LT
Patkar, AA
Gorelick, DA
AF Mannelli, Paolo
Peindl, Kathleen
Wu, Li-Tzy
Patkar, Ashwin A.
Gorelick, David A.
TI The Combination Very Low-Dose Naltrexone-Clonidine in the Management of
Opioid Withdrawal
SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
LA English
DT Article
DE addiction; detoxification; antagonist; adrenergic; pharmacotherapies
ID NALOXONE-PRECIPITATED WITHDRAWAL; OPIATE WITHDRAWAL; DETOXIFICATION;
METHADONE; LOFEXIDINE; ADDICTION; RECEPTORS
AB Background: The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives: We investigated the effects of a VLNTX-clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods: Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1-.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results: VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance: Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal.
C1 [Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA.
[Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
RP Mannelli, P (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 2218 Elder St,Suite 123, Durham, NC 27705 USA.
EM paolo.mannelli@duke.edu
FU Intramural NIH HHS; NIDA NIH HHS [DA15469, R21 DA015469, U10 DA013727]
NR 29
TC 1
Z9 1
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0095-2990
J9 AM J DRUG ALCOHOL AB
JI Am. J. Drug Alcohol Abuse
PD MAY
PY 2012
VL 38
IS 3
BP 200
EP 205
DI 10.3109/00952990.2011.644003
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 923RT
UT WOS:000302637200002
PM 22233189
ER
PT J
AU Shah, R
Diaz, SD
Arria, A
LaGasse, LL
Derauf, C
Newman, E
Smith, LM
Huestis, MA
Haning, W
Strauss, A
Della Grotta, S
Dansereau, LM
Roberts, MB
Neal, C
Lester, BM
AF Shah, Rizwan
Diaz, Sabrina D.
Arria, Amelia
LaGasse, Linda L.
Derauf, Chris
Newman, Elana
Smith, Lynne M.
Huestis, Marilyn A.
Haning, William
Strauss, Arthur
Della Grotta, Sheri
Dansereau, Lynne M.
Roberts, Mary B.
Neal, Charles
Lester, Barry M.
TI Prenatal Methamphetamine Exposure and Short-Term Maternal and Infant
Medical Outcomes
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE amphetamine; methamphetamine; drug; antenatal; neonate
ID LIFE-STYLE; AMPHETAMINE ADDICTION; PSYCHIATRIC-SYMPTOMS; INTRAUTERINE
GROWTH; PREGNANT-WOMEN; FETAL-GROWTH; ENVIRONMENT; ABUSE; DRUGS
AB Objective Examine maternal and infant medical outcomes of prenatal exposure to methamphetamine (MA).
Study Design Four hundred and twelve mother-infant pairs (204 MA-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. Exposure was determined by maternal self-report during this pregnancy and/or positive meconium toxicology. Maternal interviews assessed prenatal drug use, pregnancy course, and sociodemographic information. Medical chart reviews provided medical history, obstetric complications, infant outcomes, and discharge placement.
Results MA-using mothers were more likely to be poor, to have a psychiatric disorder/emotional illness and less prenatal care, and to be less likely to breast-feed their infant than comparison mothers. After adjusting for covariates, MA-exposed infants were more likely to exhibit poor suck, to have smaller head circumferences and length, to require neonatal intensive care unit (NICU) admission, and to be referred to child protective services (CPS). Several outcomes previously reported from studies that lacked adequate control groups or adjustment for covariates were not significantly different in this study.
Conclusion Prenatal MA exposure is associated with maternal psychiatric disorder/emotional illness, poor suck, NICU admission, and CPS involvement, and MA-exposed infants were less likely to be breast-fed; however, the absence of many serious complications, such as fetal distress, chronic hypertension, preeclampsia, placenta previa, abruptio placentae, and cardiac defects, suggests confounding variables influenced prior studies.
C1 [Diaz, Sabrina D.; Smith, Lynne M.] Harbor UCLA Med Ctr, LABiomed Inst, Los Angeles, CA USA.
[Diaz, Sabrina D.; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Shah, Rizwan] Iowa Hlth, Blank Hosp Reg Child Protect Ctr, Des Moines, IA USA.
[Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA.
[LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Roberts, Mary B.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI USA.
[Derauf, Chris; Haning, William; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Strauss, Arthur] Long Beach Mem Med Ctr, Miller Childrens Hosp, Long Beach, CA USA.
RP Diaz, SD (reprint author), Harbor UCLA Med Ctr, 1124 W Carson St,RB 1, Torrance, CA 90502 USA.
EM scopes@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265
FU National Institute on Drug Abuse [R01DA014918]; National Center on
Research Resources [M01RR00425, U54RR026136]
FX This study was supported by grants from the National Institute on Drug
Abuse (R01DA014918) and the National Center on Research Resources
(M01RR00425 and U54RR026136).
NR 37
TC 10
Z9 11
U1 2
U2 17
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAY
PY 2012
VL 29
IS 5
BP 391
EP 400
DI 10.1055/s-0032-1304818
PG 10
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 928DV
UT WOS:000302962200011
PM 22399214
ER
PT J
AU Shizukuda, Y
Smith, KP
Tripodi, DJ
Arena, R
Yau, YY
Bolan, CD
Waclawiw, MA
Leitman, SF
Rosing, DR
AF Shizukuda, Yukitaka
Smith, Kevin P.
Tripodi, Dorothy J.
Arena, Ross
Yau, Yu-Ying
Bolan, Charles D.
Waclawiw, Myron A.
Leitman, Susan F.
Rosing, Douglas R.
TI Changes in Exercise Capacity in Subjects with Cardiac Asymptomatic
Hereditary Hemochromatosis During a Follow-Up After 5 yrs
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Hereditary Hemochromatosis; Exercise Capacity; Cardiopulmonary Exercise
Test; Prospective Study
ID HEART-FAILURE; VENTILATORY EFFICIENCY; ECHOCARDIOGRAPHY; MANAGEMENT;
THRESHOLD; TREADMILL; INDEXES; STRESS; HFE
AB Shizukuda Y, Smith KP, Tripodi DJ, Arena R, Yau Y-Y, Bolan CD, Waclawiw MA, Leitman SF, Rosing DR: Changes in exercise capacity in subjects with cardiac asymptomatic hereditary hemochromatosis during a follow-up after 5 yrs. Am J Phys Med Rehabil 2012;91:418-424.
Objective: A long-term effect of hereditary hemochromatosis (HH) on aerobic exercise capacity (AEC) has not been well described.
Design: Forty-three HH and 21 volunteer control subjects who were asymptomatic underwent cardiopulmonary exercise testing using the Bruce protocol. AEC was assessed with minute ventilation ((V) over dotE), oxygen uptake ((V) over dotO(2)), and carbon dioxide production ((V) over dotCO(2)) at baseline and at a follow-up assessment after 5 yrs. A paired t test was used for analyses of normality data; otherwise, Wilcoxon's signed rank-sum test was used.
Results: Thirty-three HH subjects and 18 volunteer control subjects returned for a repeat cardiopulmonary exercise testing at the fifth-year follow-up (80% overall return rate). At the fifth-year follow-up, AEC was not different between the two groups. Compared with baseline measurements, exercise time, peak (V) over dotO(2), and the (V) over dotE/(V) over dotCO(2) slope did not differ statistically at the fifth-year follow-up between both groups. Iron depletion through phlebotomy for 5 yrs did not significantly affect AEC in newly diagnosed HH subjects at baseline (n = 14) and cardiac arrhythmias during exercise tended to decrease after 5 yrs of therapy in this group.
Conclusions: The AEC of asymptomatic HH subjects treated using conventional therapy is not statistically affected by the disease during a 5-yr period.
C1 [Shizukuda, Yukitaka] Univ Cincinnati, Dept Internal Med, Div Cardiovasc Dis, Cincinnati, OH 45267 USA.
[Shizukuda, Yukitaka; Smith, Kevin P.; Tripodi, Dorothy J.; Rosing, Douglas R.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Shizukuda, Yukitaka] Cincinnati VA Med Ctr, Cincinnati, OH USA.
[Arena, Ross] Univ New Mexico, Dept Orthopaed, Phys Therapy Program, Albuquerque, NM 87131 USA.
[Yau, Yu-Ying; Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bolan, Charles D.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Waclawiw, Myron A.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Shizukuda, Y (reprint author), Univ Cincinnati, Dept Internal Med, Div Cardiovasc Dis, 231 Albert Sabin Way,ML 0542, Cincinnati, OH 45267 USA.
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
FU Intramural NIH HHS [Z99 HL999999]; NCI NIH HHS [R01 CA094118]
NR 30
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD MAY
PY 2012
VL 91
IS 5
BP 418
EP 424
DI 10.1097/PHM.0b013e3182465f5f
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 929IH
UT WOS:000303054000006
PM 22311055
ER
PT J
AU Shavers, VL
Klein, WMP
Fagan, P
AF Shavers, Vickie L.
Klein, William M. P.
Fagan, Pebbles
TI Research on Race/Ethnicity and Health Care Discrimination: Where We Are
and Where We Need to Go
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Shavers, Vickie L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Fagan, Pebbles] Univ Hawaii, Canc Prevent & Control Program, Ctr Canc, Honolulu, HI 96822 USA.
RP Shavers, VL (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN Room 4005, Bethesda, MD 20892 USA.
EM shaversv@mail.nih.gov
NR 18
TC 15
Z9 15
U1 0
U2 10
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 MAY
PY 2012
VL 102
IS 5
BP 930
EP 932
DI 10.2105/AJPH.2012.300708
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 928FT
UT WOS:000302969300027
PM 22494001
ER
PT J
AU Shavers, VL
Fagan, P
Jones, D
Klein, WMP
Boyington, J
Moten, C
Rorie, E
AF Shavers, Vickie L.
Fagan, Pebbles
Jones, Dionne
Klein, William M. P.
Boyington, Josephine
Moten, Carmen
Rorie, Edward
TI The State of Research on Racial/Ethnic Discrimination in The Receipt of
Health Care
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID PERCEIVED RACIAL-DISCRIMINATION; AFRICAN-AMERICAN MEN;
BLACK-WOMENS-HEALTH; QUALITY-OF-CARE; ETHNIC-MINORITIES;
MEDICAL-STUDENTS; CULTURAL COMPETENCE; COMMUNITY SAMPLE; BLOOD-PRESSURE;
ASSOCIATION
AB Objectives. We conducted a review to examine current literature on the effects of interpersonal and institutional racism and discrimination occurring within health care settings on the health care received by racial/ethnic minority patients.
Methods. We searched the Psych Net, PubMed, and Scopus databases for articles on US populations published between January 1, 2008 and November 1, 2011. We used various combinations of the following search terms: discrimination, perceived discrimination, race, ethnicity, racism, institutional racism, stereotype, prejudice or bias, and health or health care. Fifty-eight articles were reviewed.
Results. Patient perception of discriminatory treatment and implicit provider biases were the most frequently examined topics in health care settings. Few studies examined the overall prevalence of racial/ethnic discrimination and none examined temporal trends. In general, measures used were insufficient for examining the impact of interpersonal discrimination or institutional racism within health care settings on racial/ethnic disparities in health care.
Conclusions. Better instrumentation, innovative methodology, and strategies are needed for identifying and tracking racial/ethnic discrimination in health care settings. (Am J Public Health. 2012;102:953-966. doi:10.2105/AJPH.2012.300773)
C1 [Shavers, Vickie L.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Fagan, Pebbles] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Boyington, Josephine] NHLBI, NIH, Bethesda, MD 20892 USA.
[Moten, Carmen] Natl Canc Inst Rockville, Ctr Reduce Canc Hlth Dispar, Rockville, MD USA.
[Rorie, Edward] Nova Res Co, Bethesda, MD USA.
RP Shavers, VL (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN Room 4005, Bethesda, MD 20892 USA.
EM shaversv@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 105
TC 71
Z9 72
U1 6
U2 43
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 MAY
PY 2012
VL 102
IS 5
BP 953
EP 966
DI 10.2105/AJPH.2012.300773
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 928FT
UT WOS:000302969300031
PM 22494002
ER
PT J
AU Zhong, MH
De Angelo, P
Osborne, L
Paniz-Mondolfi, AE
Geller, M
Yang, YF
Linehan, WM
Merino, MJ
Cordon-Cardo, C
Cai, DM
AF Zhong, Minghao
De Angelo, Patricia
Osborne, Lisa
Paniz-Mondolfi, Alberto E.
Geller, Matthew
Yang, Youfeng
Linehan, W. Marston
Merino, Maria J.
Cordon-Cardo, Carlos
Cai, Dongming
TI Translocation Renal Cell Carcinomas in Adults: A Single-institution
Experience
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE translocation renal cell carcinoma; TFE3; TFEB
ID OF-THE-LITERATURE; SOFT PART SARCOMA; TFE3 GENE FUSIONS; KIDNEY CANCER;
MELANOMA; MITF; NEOPLASMS; IMMUNOHISTOCHEMISTRY; DIAGNOSIS; ONCOGENE
AB Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20% to 40% of pediatric RCCs, with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathologic features of adult translocation RCC from a single institution. Using tissue microarray, immunohistochemistry, cytogenetic examination, and fluorescence in situ hybridization, we identified 6 (similar to 5%) cases of TFE3 translocation RCC and 1 (< 1%) case of TFEB translocation RCC in 121 consecutive adult RCC cases between 2001 and 2009. Our results suggest that weak TFE3 staining of a significant proportion of RCC cases may be because of expression of the full-length TFE3 protein rather than the chimeric fusion protein resulting from chromosomal translocation.
C1 [Zhong, Minghao; Cordon-Cardo, Carlos; Cai, Dongming] Mt Sinai Sch Med, New York, NY 10029 USA.
[Paniz-Mondolfi, Alberto E.] St Lukes Roosevelt Hosp, New York, NY USA.
[Geller, Matthew] Winthrop Univ Hosp, Mineola, NY 11501 USA.
[Zhong, Minghao] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ 07103 USA.
[De Angelo, Patricia; Osborne, Lisa] Univ Med & Dent New Jersey, New Jersey Med Sch, Inst Genom Med, Newark, NJ 07103 USA.
[Yang, Youfeng; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zhong, MH (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA.
EM minghaozhong@gmail.com
FU NJMS Pathology Department
FX This study was partly supported by the NJMS Pathology Department
Resident Research Fund.
NR 34
TC 28
Z9 32
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAY
PY 2012
VL 36
IS 5
BP 654
EP 662
DI 10.1097/PAS.0b013e31824f24a6
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 926EL
UT WOS:000302814000002
PM 22446944
ER
PT J
AU Eberle, FC
Song, JY
Xi, LQ
Raffeld, M
Harris, NL
Wilson, WH
Pittaluga, S
Jaffe, ES
AF Eberle, Franziska C.
Song, Joo Y.
Xi, Liqiang
Raffeld, Mark
Harris, Nancy Lee
Wilson, Wyndham H.
Pittaluga, Stefania
Jaffe, Elaine S.
TI Nodal Involvement by Cutaneous CD30-positive T-cell Lymphoma Mimicking
Classical Hodgkin Lymphoma
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE CD30-positive T-cell lymphoma; classical Hodgkin lymphoma; lymphomatoid
papulosis; mycosis fungoides; transformation; primary cutaneous
CD30-positive T-cell lymphoproliferative; disorder
ID REED-STERNBERG CELLS; MYCOSIS-FUNGOIDES; GENE REARRANGEMENTS; MOLECULAR
EVIDENCE; ACTIVATOR PROTEIN; DISEASE; PAPULOSIS; EXPRESSION; FEATURES;
ORIGIN
AB An association between classical Hodgkin lymphoma (cHL) and mycosis fungoides (MF) or lymphomatoid papulosis has been reported in the literature. However, there can be considerable morphologic and immunophenotypic overlap between cHL and nodal involvement by CD30-positive T-cell lymphoproliferative disorders (CD30-T-LPD). To examine this potential association, biopsies from patients with a history of MF or primary cutaneous CD30-T-LPD and lymph node biopsies reported as either CD30-positive T-cell lymphoma (TCL) with Hodgkin-like cells or cHL were retrieved from the authors' institution. Of 11 cases identified, 10 were considered CD30-positive TCL with Hodgkin-like cells, whereas 1 was confirmed as cHL upon review. Five cases originally diagnosed as cHL were revised as CD30-positive TCL. Cases of CD30-positive TCL with Hodgkin-like cells showed a male predominance (M:F, 4:1) with a median age of 53 years (range, 44 to 72 y). Nearly all patients (9/10) initially presented with skin lesions. In 7/10 patients the draining lymph node was involved, whereas in 3 cases this could not be confirmed. Tumor cells morphologically resembled Hodgkin/Reed-Sternberg cells; they were uniformly strongly positive for CD30, and CD15 was expressed in 9/10 (90%) cases. A T-cell derivation was confirmed by T-cell antigen expression (7/10) and clonal rearrangement of T-cell receptor genes (9/10). In 3 cases a common T-cell clone was identified in skin and lymph node. B-cell markers (CD20/PAX5) were consistently negative. In 1 case the diagnosis of cHL followed by lymphomatoid papulosis was confirmed, with Hodgkin/Reed-Sternberg cells expressing PAX5, CD30, and CD15. In situ hybridization studies for Epstein Barr virus were negative. We show that cHL is less often associated with MF and primary cutaneous CD30-T-LPD than previously thought and that the coexpression of CD30 and CD15 in these TCLs may lead to a mistaken diagnosis of cHL.
C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
EM ejaffe@mail.nih.gov
RI Song, Joo/E-5356-2016;
OI Song, Joo/0000-0003-3497-2513; Jaffe, Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute, NIH
FX Supported by funding from the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH. The authors have
disclosed that they have no significant relationships with, or financial
interest in, any commercial companies pertaining to this article.
NR 28
TC 16
Z9 16
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAY
PY 2012
VL 36
IS 5
BP 716
EP 725
DI 10.1097/PAS.0b013e3182487158
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 926EL
UT WOS:000302814000009
PM 22367293
ER
PT J
AU Cui, L
Wang, ZL
Jiang, HY
Parker, D
Wang, HY
Su, XZ
Cui, LW
AF Cui, Long
Wang, Zenglei
Jiang, Hongying
Parker, Daniel
Wang, Haiyan
Su, Xin-Zhuan
Cui, Liwang
TI Lack of Association of the S769N Mutation in Plasmodium falciparum SERCA
(PfATP6) with Resistance to Artemisinins
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IN-VITRO SENSITIVITY; MALARIA PARASITES; THALASSEMIC ERYTHROCYTES;
COMBINATION THERAPIES; NA+/H+ EXCHANGER; DRUG-RESISTANCE; POINT
MUTATIONS; MYANMAR BORDER; GENE; BINDING
AB The recent emergence of artemisinin (ART) resistance in Plasmodium falciparum in western Cambodia, manifested as delayed parasite clearance, is a big threat to the long-term efficacy of this family of antimalarial drugs. Among the multiple candidate genes associated with ART resistance in P. falciparum, the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase PfATP6 has been postulated as a specific target of ARTs. The PfATP6 gene harbors multiple single-nucleotide polymorphisms in field parasite populations, and S769N has been associated with decreased sensitivity to artemether in parasite populations from French Guiana. In this study, we used an allelic exchange strategy to engineer parasite lines carrying the S769N mutations in P. falciparum strain 3D7 and evaluated whether introduction of this mutation modulated parasite sensitivity to ART derivatives. Using three transgenic lines carrying the 769N mutation and two transgenic lines carrying the wild-type 769S as controls, we found that S769N did not affect PfATP6 gene expression. We compared the sensitivities of these parasite lines to three ART derivatives, artemether, artesunate, and dihydroartemisinin, in 18 biological experiments and detected no significant effect of the S769N mutation on parasite response to these ART derivatives. This study provides further evidence for the lack of association of PfATP6 with ART resistance.
C1 [Cui, Long; Wang, Zenglei; Parker, Daniel; Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Jiang, Hongying; Su, Xin-Zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Wang, Haiyan] Kansas State Univ, Dept Stat, Manhattan, KS 66506 USA.
RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
EM luc2@psu.edu
RI Parker, Daniel/B-5471-2013;
OI Parker, Daniel/0000-0002-5352-7338; Su, Xinzhuan/0000-0003-3246-3248
FU NIAID, NIH [1R21AI085518, U19AI089672]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by NIAID, NIH (1R21AI085518 and U19AI089672) and
by the Intramural Research Program of the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 64
TC 18
Z9 20
U1 0
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAY
PY 2012
VL 56
IS 5
BP 2546
EP 2552
DI 10.1128/AAC.05943-11
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 925VQ
UT WOS:000302790400046
PM 22354307
ER
PT J
AU Vanpouille, C
Lisco, A
Introini, A
Grivel, JC
Munawwar, A
Merbah, M
Schinazi, RF
Derudas, M
McGuigan, C
Balzarini, J
Margolis, L
AF Vanpouille, Christophe
Lisco, Andrea
Introini, Andrea
Grivel, Jean-Charles
Munawwar, Arshi
Merbah, Melanie
Schinazi, Raymond F.
Derudas, Marco
McGuigan, Christopher
Balzarini, Jan
Margolis, Leonid
TI Exploiting the Anti-HIV-1 Activity of Acyclovir: Suppression of Primary
and Drug-Resistant HIV Isolates and Potentiation of the Activity by
Ribavirin
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS;
REVERSE-TRANSCRIPTASE INHIBITOR; DUALLY INFECTED PERSONS; HSV
SUPPRESSION; HEPATITIS-C; RNA LEVELS; IN-VIVO; THERAPY; VALACYCLOVIR
AB Multiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infected ex vivo. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings.
C1 [Vanpouille, Christophe; Lisco, Andrea; Introini, Andrea; Grivel, Jean-Charles; Merbah, Melanie; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Munawwar, Arshi] All India Inst Med Sci, Dept Lab Med, Div Clin Microbiol, New Delhi, India.
[Schinazi, Raymond F.] Emory Univ, Sch Med, Vet Affairs Med Ctr, Ctr AIDS Res,Dept Pediat, Decatur, GA 30033 USA.
[Derudas, Marco; McGuigan, Christopher] Cardiff Univ, Sch Pharm, Cardiff, S Glam, Wales.
[Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium.
RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM margolis@helix.nih.gov
RI McGuigan, Chris/P-1580-2014; Schinazi, Raymond/B-6777-2017;
OI McGuigan, Chris/0000-0001-8409-710X; Introini,
Andrea/0000-0002-9929-8964
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; KU Leuven (GOA) [10/14]; NIH
[5P30-AI-50409]; Department of Veterans Affairs
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, and the KU Leuven (GOA no.
10/14). Also, this work was supported in part by NIH grant 5P30-AI-50409
(R. F. S.) and by the Department of Veterans Affairs (R.F.S.).
NR 45
TC 6
Z9 7
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAY
PY 2012
VL 56
IS 5
BP 2604
EP 2611
DI 10.1128/AAC.05986-11
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 925VQ
UT WOS:000302790400055
PM 22314523
ER
PT J
AU Schlett, CL
Ferencik, M
Kriegel, MF
Bamberg, F
Ghoshhajra, BB
Joshi, SB
Nagurney, JT
Fox, CS
Truong, QA
Hoffmann, U
AF Schlett, Christopher L.
Ferencik, Maros
Kriegel, Matthias F.
Bamberg, Fabian
Ghoshhajra, Brian B.
Joshi, Subodh B.
Nagurney, John T.
Fox, Caroline S.
Truong, Quynh A.
Hoffmann, Udo
TI Association of pericardial fat and coronary high-risk lesions as
determined by cardiac CT
SO ATHEROSCLEROSIS
LA English
DT Article
DE Coronary artery disease; Cardiac CT angiography; Peri-cardial fat;
Adipose tissue; Vulnerable plaque; High-risk lesions
ID EPICARDIAL ADIPOSE-TISSUE; MULTIDETECTOR COMPUTED-TOMOGRAPHY; VISCERAL
ABDOMINAL FAT; ACUTE CHEST-PAIN; ARTERY-DISEASE; INTRAVASCULAR
ULTRASOUND; ATHEROSCLEROTIC PLAQUE; NONINVASIVE ASSESSMENT; ANGIOGRAPHY;
CALCIFICATION
AB Objective: Pericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT.
Methods: We included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of -190 to -30 HU within the pericardial sac.
Results: Based on cardiac CT, 50% of the patients (n = 180) had no CAD, 46% (n = 165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0-179.4] cm(3) vs. 110.0 [81.5-137.4] cm(3), vs. 74.8 [58.2-111.7] cm(3), respectively p = 0.04 and p < 0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p < 0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor.
Conclusion: PAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Schlett, Christopher L.; Ghoshhajra, Brian B.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Ferencik, Maros; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Schlett, Christopher L.; Ferencik, Maros; Kriegel, Matthias F.; Ghoshhajra, Brian B.; Joshi, Subodh B.; Nagurney, John T.; Fox, Caroline S.; Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, 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, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
EM uhoffmann@partners.org
RI 王, 强/F-4212-2011
FU NHLBI NIH HHS [L30 HL093806, K23 HL098370]
NR 42
TC 25
Z9 25
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAY
PY 2012
VL 222
IS 1
BP 129
EP 134
DI 10.1016/j.atherosclerosis.2012.02.029
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 928DJ
UT WOS:000302960600020
PM 22417843
ER
PT J
AU Wassel, CL
Lamina, C
Nambi, V
Coassin, S
Mukamal, KJ
Ganesh, SK
Jacobs, DR
Franceschini, N
Papanicolaou, GJ
Gibson, Q
Yanek, LR
van der Harst, P
Ferguson, JF
Crawford, DC
Waite, LL
Allison, MA
Criqui, MH
McDermott, MM
Mehra, R
Cupples, LA
Hwang, SJ
Redline, S
Kaplan, RC
Heiss, G
Rotter, JI
Boerwinkle, E
Taylor, HA
Eraso, LH
Haun, M
Li, MY
Meisinger, C
O'Connell, JR
Shuldineri, AR
Tybjaerg-Hansen, A
Frikke-Schmidt, R
Kollerits, B
Rantner, B
Dieplinger, B
Stadler, M
Mueller, T
Haltmayer, M
Klein-Weigel, P
Summerer, M
Wichmann, HE
Asselbergs, FW
Navis, G
Leach, IM
Brown-Gentry, K
Goodloe, R
Assimes, TL
Becker, DM
Cooke, JP
Absher, DM
Olin, JW
Mitchell, BD
Reilly, MP
Mohler, ER
North, KE
Reiner, AP
Kronenberg, F
Murabito, JM
AF Wassel, Christina L.
Lamina, Claudia
Nambi, Vijay
Coassin, Stefan
Mukamal, Kenneth J.
Ganesh, Santhi K.
Jacobs, David R., Jr.
Franceschini, Nora
Papanicolaou, George J.
Gibson, Quince
Yanek, Lisa R.
van der Harst, Pim
Ferguson, Jane F.
Crawford, Dana C.
Waite, Lindsay L.
Allison, Matthew A.
Criqui, Michael H.
McDermott, Mary M.
Mehra, Reena
Cupples, L. Adrienne
Hwang, Shih-Jen
Redline, Susan
Kaplan, Robert C.
Heiss, Gerardo
Rotter, Jerome I.
Boerwinkle, Eric
Taylor, Herman A.
Eraso, Luis H.
Haun, Margot
Li, Mingyao
Meisinger, Christa
O'Connell, Jeffrey R.
Shuldineri, Alan R.
Tybjaerg-Hansen, Anne
Frikke-Schmidt, Ruth
Kollerits, Barbara
Rantner, Barbara
Dieplinger, Benjamin
Stadler, Marietta
Mueller, Thomas
Haltmayer, Meinhard
Klein-Weigel, Peter
Summerer, Monika
Wichmann, H. -Erich
Asselbergs, Folkert W.
Navis, Gerjan
Leach, Irene Mateo
Brown-Gentry, Kristin
Goodloe, Robert
Assimes, Themistocles L.
Becker, Diane M.
Cooke, John P.
Absher, Devin M.
Olin, Jeffrey W.
Mitchell, Braxton D.
Reilly, Muredach P.
Mohler, Emile R., III
North, Kari E.
Reiner, Alexander P.
Kronenberg, Florian
Murabito, Joanne M.
TI Genetic determinants of the ankle-brachial index: A meta-analysis of a
cardiovascular candidate gene 50K SNP panel in the candidate gene
association resource (CARe) consortium
SO ATHEROSCLEROSIS
LA English
DT Article
DE Ankle brachial index; Peripheral artery disease; Genetics; Candidate
gene array; Meta-analysis; Ethnicity
ID PERIPHERAL ARTERIAL-DISEASE; GENOME-WIDE ASSOCIATION; RISK LOCI;
APOLIPOPROTEIN(A) ISOFORMS; INSULIN-RESPONSE; FAMILY-HISTORY;
SUSCEPTIBILITY; LIPOPROTEIN(A); POPULATION; ATHEROTHROMBOSIS
AB Background: Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of similar to 50,000 SNPs across similar to 2100 candidate genes to identify genetic variants for ABI.
Methods and results: We studied subjects of European ancestry from 8 studies (n = 21,547, 55% women, mean age 44-73 years) and African American ancestry from 5 studies (n = 7267, 60% women, mean age 41-73 years) involved in the candidate gene association resource (CARe) consortium. In each ethnic group, additive genetic models were used (with each additional copy of the minor allele corresponding to the given beta) to test each SNP for association with continuous ABI (excluding ABI > 1.40) and PAD (defined as ABI < 0.90) using linear or logistic regression with adjustment for known PAD risk factors and population stratification. We then conducted a fixed-effects inverse-variance weighted meta-analyses considering a p < 2 x 10(-6) to denote statistical significance.
Results: In the European ancestry discovery meta-analyses, rs2171209 in SYTL3 (beta = -0.007, p = 6.02 x 10(-7)) and rs290481 in TCF7L2 (beta = -0.008, p = 7.01 x 10(-7)) were significantly associated with ABI. None of the SNP associations for PAD were significant, though a SNP in CYP2B6 (p = 4.99 x 10(-5)) was among the strongest associations. These 3 genes are linked to key PAD risk factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We sought replication in 6 population-based and 3 clinical samples (n = 15,440) for rs290481 and rs2171209. However, in the replication stage (rs2171209, p = 0.75; rs290481, p = 0.19) and in the combined discovery and replication analysis the SNP-ABI associations were no longer significant (rs2171209, p = 1.14 x 10(-3); rs290481, p = 8.88 x 10(-5)). In African Americans, none of the SNP associations for ABI or PAD achieved an experiment-wide level of significance.
Conclusions: Genetic determinants of ABI and PAD remain elusive. Follow-up of these preliminary findings may uncover important biology given the known gene-risk factor associations. New and more powerful approaches to PAD gene discovery are warranted. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Wassel, Christina L.; Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, La Jolla, CA 92093 USA.
[Lamina, Claudia; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Rantner, Barbara; Summerer, Monika; Kronenberg, Florian] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
[Nambi, Vijay] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Ganesh, Santhi K.] Univ Michigan Hlth Care Syst, Deparment Internal Med, Div Cardiovasc Med, Ann Arbor, MI USA.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA.
[Franceschini, Nora; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Gillings Global Sch Publ Hlth, Chapel Hill, NC USA.
[Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Gibson, Quince; O'Connell, Jeffrey R.; Shuldineri, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21201 USA.
[Yanek, Lisa R.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.
[van der Harst, Pim; Leach, Irene Mateo] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Ferguson, Jane F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Waite, Lindsay L.; Absher, Devin M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Mehra, Reena] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hwang, Shih-Jen] NHLBI, Framingham Heart Study, Ctr Populat Study, Framingham, MA USA.
[Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med, Boston, MA 02115 USA.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Taylor, Herman A.] Jackson State Univ, Jackson, MS USA.
[Eraso, Luis H.] Thomas Jefferson Univ Hosp, Jefferson Vasc Ctr, Philadelphia, PA 19107 USA.
[Li, Mingyao] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Shuldineri, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Tybjaerg-Hansen, Anne; Frikke-Schmidt, Ruth] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
[Rantner, Barbara] Innsbruck Med Univ, Dept Vasc Surg, Innsbruck, Austria.
[Dieplinger, Benjamin; Mueller, Thomas; Haltmayer, Meinhard] Konventhosp Barmherzige Brueder Linz, Dept Lab Med, Linz, Austria.
[Stadler, Marietta] Hietzing Hosp, Med Dept Metab Dis & Nephrol 3, Vienna, Austria.
[Klein-Weigel, Peter] DRK Kliniken Berlin Mitte, Klin Innere Med Schwerpunkt Angiol, Berlin, Germany.
[Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
[Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Asselbergs, Folkert W.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands.
[Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Assimes, Themistocles L.; Cooke, John P.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Olin, Jeffrey W.] Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.
[Olin, Jeffrey W.] Mt Sinai Sch Med, Marie Joseie & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA.
[Mohler, Emile R., III] Univ Penn, Div Cardiol, Vasc Med Sect, Perelman Sch Med, Philadelphia, PA 19104 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Reiner, Alexander P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Murabito, Joanne M.] NHLBI, Framingham Heart Study, Boston, MA USA.
RP Murabito, JM (reprint author), 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM Murabito@bu.edu
RI Ferguson, Jane/C-7154-2011; Crawford, Dana/C-1054-2012; Meisinger,
Christine/B-5358-2014; Kronenberg, Florian/B-1736-2008;
OI Mitchell, Braxton/0000-0003-4920-4744; Cooke, John/0000-0003-0033-9138;
Meisinger, Christa/0000-0002-9026-6544; Allison,
Matthew/0000-0003-0777-8272; Ferguson, Jane/0000-0001-6896-1025;
Kronenberg, Florian/0000-0003-2229-1120; Eraso,
Luis/0000-0002-7890-4902; Murabito, Joanne/0000-0002-0192-7516; Cupples,
L. Adrienne/0000-0003-0273-7965; Mehra, Reena/0000-0002-6222-2675
FU National Institutes of Health (NIH)/National Heart Lung and Blood
Institute (NHLBI) [HHSN268200625226C, 5215810-55000000041]
FX The Candidate Gene Association Resource (CARe) is supported by contract
number HHSN268200625226C from the National Institutes of Health
(NIH)/National Heart Lung and Blood Institute (NHLBI), and subcontract
number 5215810-55000000041 to C.L.W. A full listing of the grants and
contracts that have supported CARe is provided at
http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. Please see
information in supplementary information file for a complete list of
funding information for each study participating in this manuscript.
NR 38
TC 7
Z9 7
U1 0
U2 5
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 MAY
PY 2012
VL 222
IS 1
BP 138
EP 147
DI 10.1016/j.atherosclerosis.2012.01.039
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 928DJ
UT WOS:000302960600022
PM 22361517
ER
PT J
AU Sengupta, P
Lippincott-Schwartz, J
AF Sengupta, Prabuddha
Lippincott-Schwartz, Jennifer
TI Quantitative analysis of photoactivated localization microscopy (PALM)
datasets using pair-correlation analysis
SO BIOESSAYS
LA English
DT Article
DE pair-correlation; PALM; quantitative analysis; super-resolution
ID DRIVEN INTRAMOLECULAR DYNAMICS; GENETICALLY EXPRESSED PROBES;
FLUORESCENT PROTEIN; DIFFRACTION-LIMIT; CELL-MEMBRANES; RESOLUTION;
MOLECULES; TRACKING; NANOSCOPY; GFP
AB Pointillistic based super-resolution techniques, such as photoactivated localization microscopy (PALM), involve multiple cycles of sequential activation, imaging, and precise localization of single fluorescent molecules. A super-resolution image, having nanoscopic structural information, is then constructed by compiling all the image sequences. Because the final image resolution is determined by the localization precision of detected single molecules and their density, accurate image reconstruction requires imaging of biological structures labeled with fluorescent molecules at high density. In such image datasets, stochastic variations in photon emission and intervening dark states lead to uncertainties in identification of single molecules. This, in turn, prevents the proper utilization of the wealth of information on molecular distribution and quantity. A recent strategy for overcoming this problem is pair-correlation analysis applied to PALM. Using rigorous statistical algorithms to estimate the number of detected proteins, this approach allows the spatial organization of molecules to be quantitatively described.
C1 [Sengupta, Prabuddha; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MA USA.
RP Sengupta, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MA USA.
EM senguptp@mail.nih.gov
OI Sengupta, Prabuddha/0000-0001-7094-6967
FU Intramural NIH HHS [Z01 HD008850-01]
NR 54
TC 31
Z9 31
U1 2
U2 27
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD MAY
PY 2012
VL 34
IS 5
SI SI
BP 396
EP 405
DI 10.1002/bies.201200022
PG 10
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 927GS
UT WOS:000302895900012
PM 22447653
ER
PT J
AU Nandurdikar, RS
Maciag, AE
Holland, RJ
Cao, Z
Shami, PJ
Anderson, LM
Keefer, LK
Saavedra, JE
AF Nandurdikar, Rahul S.
Maciag, Anna E.
Holland, Ryan J.
Cao, Zhao
Shami, Paul J.
Anderson, Lucy M.
Keefer, Larry K.
Saavedra, Joseph E.
TI Structural modifications modulate stability of glutathione-activated
arylated diazeniumdiolate prodrugs
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Nitric oxide; Diazeniumdiolate prodrugs; JS-K; Glutathione; Anti-cancer
agents
ID JS-K; IN-VITRO; VIVO; CELLS
AB JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo anti-tumor activity. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Nandurdikar, Rahul S.; Holland, Ryan J.; Anderson, Lucy M.; Keefer, Larry K.] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
[Maciag, Anna E.; Cao, Zhao; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Shami, Paul J.] Univ Utah, Div Hematol & Hematol Malignancies, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
RP Nandurdikar, RS (reprint author), NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
EM nandurdikarr@mail.nih.gov; saavedjo@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E and by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. We thank Dr.
Sergey Tarasov and Ms. Marzena A. Dyba of the Biophysics Resource in the
Structural Biophysics Laboratory, NCI-Frederick, for assistance with the
high resolution mass spectrometry studies. We thank Mr. Ken Kosak of the
University of Utah for providing the Pluronics P123 formulation.
NR 7
TC 8
Z9 8
U1 1
U2 8
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 MAY 1
PY 2012
VL 20
IS 9
BP 3094
EP 3099
DI 10.1016/j.bmc.2012.02.045
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 928RW
UT WOS:000303002100036
PM 22480849
ER
PT J
AU Lovell, KM
Vasiljevik, T
Araya, JJ
Lozama, A
Prevatt-Smith, KM
Day, VW
Dersch, CM
Rothman, RB
Butelman, ER
Kreek, MJ
Prisinzano, TE
AF Lovell, Kimberly M.
Vasiljevik, Tamara
Araya, Juan J.
Lozama, Anthony
Prevatt-Smith, Katherine M.
Day, Victor W.
Dersch, Christina M.
Rothman, Richard B.
Butelman, Eduardo R.
Kreek, Mary Jeanne
Prisinzano, Thomas E.
TI Semisynthetic neoclerodanes as kappa opioid receptor probes
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Natural product; Salvinorin A; Salvia divinorum; Kappa opioid receptor;
Hallucinogen; Furan
ID SALVINORIN-A; SALVIA-DIVINORUM; NATURAL-PRODUCTS; RHESUS-MONKEYS;
LIGANDS; AGONIST; ANTAGONISTS; DITERPENES; COCAINE; TRANSFORMATIONS
AB Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as Grignard and Stille conditions, have met with limited success. We report a palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a boronic acid that occurs at neutral pH and ambient temperature to produce ketone analogs at C-12. To the best of our knowledge, this is the first reported usage of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through microwave irradiation. Previously, this synthetically challenging process has required multiple steps. Additionally, we report in this study that alkene 9 and aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2-yl analog of 1 (31) has similar affinity to 1. Collectively, these findings suggest that different aromatic groups appended directly to the decalin core may be well tolerated by KOP receptors, and may generate further ligands with affinity and activity at KOP receptors. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Lovell, Kimberly M.; Vasiljevik, Tamara; Araya, Juan J.; Prevatt-Smith, Katherine M.; Day, Victor W.; Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
[Lozama, Anthony] Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA.
[Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, IRP, DHHS, Baltimore, MD 21224 USA.
[Butelman, Eduardo R.; Kreek, Mary Jeanne] Rockefeller Univ, Lab Biol Addict Dis, New York, NY USA.
RP Prisinzano, TE (reprint author), Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
EM prisinza@ku.edu
FU National Institute on Drug Abuse [DA018151, DA05130, DA011113]; NIH
[GM008545]; National Science Foundation [CHE-0923449]; University of
Kansas; National Institute on Drug Abuse, NIH, DHHS
FX The authors thank the National Institute on Drug Abuse (DA018151 to TEP,
DA05130 to MJK, and DA011113 to ERB) and the NIH Dynamic Aspects of
Chemical Biology training grant (GM008545 to KML and KPS) for financial
support of ongoing research, and the National Science Foundation
(CHE-0923449) and the University of Kansas for funds to purchase the
x-ray instrumentation and computers. Portions of this work were
supported by the Intramural Research Program, National Institute on Drug
Abuse, NIH, DHHS. The content is the sole responsibility of the authors
and does not necessarily represent the official views of the National
Institute on Drug Abuse, National Institutes of Health, or the National
Science Foundation. The authors also thank Dr. Alfredo Ortega and Elihu
Bautista for the pictures of Salvia sp.
NR 51
TC 14
Z9 14
U1 0
U2 28
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 MAY 1
PY 2012
VL 20
IS 9
BP 3100
EP 3110
DI 10.1016/j.bmc.2012.02.040
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 928RW
UT WOS:000303002100037
PM 22464684
ER
PT J
AU Tadmor, T
Liphshitz, I
Aviv, A
Landgren, O
Barchana, M
Polliack, A
AF Tadmor, Tamar
Liphshitz, Irena
Aviv, Ariel
Landgren, Ola
Barchana, Micha
Polliack, Aaron
TI Increased incidence of chronic lymphocytic leukaemia and lymphomas in
patients with Merkel cell carcinoma - a population based study of 335
cases with neuroendocrine skin tumour
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Merkel cell carcinoma; haematological neoplasias; chronic; small cell
lymphocytic leukaemia (CLL; CLL); lymphomas; malignancies
ID POLYOMAVIRUS; CANCERS; RITUXIMAB
AB Merkel cell carcinoma (MCC) is a rare aggressive skin tumour that appears to be associated with a large number of other tumours. We collected all reported cases in Israel and estimated its association with other tumours, including haematological malignancies. The population based Israel Cancer Registry identified 335 patients with MCC diagnosed between1989 and 2010. Ninety-seven percent were in the Jewish population; median age at diagnosis for Jewish patients was 73.4 and 55.6 years for the Arab population. Other associated malignancies were encountered in 92 patients (27.4%) with MCC (90 Jews, two Arabs). Of the Jewish cases, 66 presented with an associated malignancy before, and 24 after, the diagnosis of MCC. Solid tumours were not significantly increased among patients with MCC. Thirty-one of these associated cancers (34.4%) were haemato-oncological malignancies, 24 were detected before and seven after the diagnosis of MCC. The standardized incidence ratio (SIR) for haematological malignancy was 3.67 for males and 3.62 for females, and the most frequent haemato-oncological neoplasias recorded were chronic lymphocytic leukaemia (45%) and lymphomas (29%). Although MCC is rare, clinicians should be aware of the possible association with B-cell lymphoproliferative disorders when evaluating patients with neuroendocrine skin tumours.
C1 [Tadmor, Tamar] Bnai Zion Med Ctr, Oncol Unit, IL-31048 Haifa, Israel.
[Liphshitz, Irena] Minist Hlth, Natl Canc Registry, Jerusalem, Israel.
[Aviv, Ariel] Emek Med Ctr, Oncol Unit, Afula, Israel.
[Landgren, Ola] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
[Barchana, Micha] Univ Haifa, Sch Publ Hlth, IL-31999 Haifa, Israel.
[Polliack, Aaron] Hadassah Univ Hosp, Dept Haematol, IL-91120 Jerusalem, Israel.
[Polliack, Aaron] Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel.
RP Tadmor, T (reprint author), Bnai Zion Med Ctr, Oncol Unit, 47 Golomb St, IL-31048 Haifa, Israel.
EM tamar.tadmor@b-zion.org.il
NR 24
TC 11
Z9 11
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 MAY
PY 2012
VL 157
IS 4
BP 457
EP 462
DI 10.1111/j.1365-2141.2012.09087.x
PG 6
WC Hematology
SC Hematology
GA 927UF
UT WOS:000302934900007
PM 22390778
ER
PT J
AU Rizzo, LV
Vallochi, AL
Belfort, R
Holland, GN
Nussenblatt, RB
AF Rizzo, Luiz Vicente
Vallochi, Adriana Lima
Belfort, Rubens
Holland, Gary N.
Nussenblatt, Robert B.
TI Toxoplasma gondii in the peripheral blood of patients with ocular
toxoplasmosis response
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Letter
C1 [Rizzo, Luiz Vicente] Hosp Israelita Albert Einstein, Sao Paulo, Brazil.
[Vallochi, Adriana Lima] Inst Oswaldo Cruz, BR-20001 Rio De Janeiro, Brazil.
[Belfort, Rubens] Univ Fed Sao Paulo, Escola Paulista Med, Dept Ophthalmol, Sao Paulo, Brazil.
[Holland, Gary N.] Univ Calif Los Angeles, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90024 USA.
[Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
[Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Rizzo, LV (reprint author), Av Albert Einstein 627-701, BR-05652000 Morumbi Sao Paulo, SP, Brazil.
EM lvrizzo@einstein.br
RI Rizzo, Luiz Vicente/B-4458-2009; Belfort Jr, Rubens/E-2252-2012
OI Belfort Jr, Rubens/0000-0002-8422-3898
NR 1
TC 0
Z9 0
U1 0
U2 3
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 MAY
PY 2012
VL 96
IS 5
BP 766
EP 766
DI 10.1136/bjophthalmol-2011-301237
PG 1
WC Ophthalmology
SC Ophthalmology
GA 927UX
UT WOS:000302936900034
ER
PT J
AU Ling, NXY
Lee, J
Ellis, M
Liao, ML
Mau, SL
Guest, D
Janssen, PH
Kovac, P
Bacic, A
Pettolino, FA
AF Ling, Naomi X. -Y.
Lee, Joanne
Ellis, Miriam
Liao, Ming-Long
Mau, Shaio-Lim
Guest, David
Janssen, Peter H.
Kovac, Pavol
Bacic, Antony
Pettolino, Filomena A.
TI An exo-beta-(1 -> 3)-D-galactanase from Streptomyces sp provides
insights into type II arabinogalactan structure
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE beta-D-Galactanases; Arabinogalactan-protein; Streptomyces sp.;
De-arabinosylated gum arabic; CAZy family GH 43
ID GUM-ARABIC GLYCOPROTEIN; METHYL BETA-GLYCOSIDES; O-GLYCOSYLATION CODES;
RAPHANUS-SATIVUS L; MOLECULAR CHARACTERIZATION; TRICHODERMA-VIRIDE;
BLOCKWISE APPROACH; ASPERGILLUS-NIGER; ACACIA-SENEGAL; PROTEINS
AB An exo-beta-(1 -> 3)-D-galactanase (SGalase1) that specifically cleaves the beta-(1 -> 3)-D-galactan backbone of arabinogalactan-proteins (AGPs) was isolated from culture filtrates of a soil Streptomyces sp. Internal peptide sequence information was used to clone and recombinantly express the gene in E. coli. The molecular mass of the isolated enzyme was similar to 45 kDa, similar to the 48.2 kDa mass predicted from the amino acid sequence. The pI, pH and temperature optima for the enzyme were similar to 7.45, 3.8 and 48 degrees C, respectively. The native and recombinant enzymes specifically hydrolysed beta-(1 -> 3)-D-galacto-oligo-or poly-saccharides from the upstream (non-reducing) end, typical of an exo-acting enzyme. A second homologous Streptomyces gene (SGalase2) was also cloned and expressed. SGalase2 was similar in size (47.9 kDa) and enzyme activity to SGalase1 but differed in its pH optimum (pH 5). Both SGalase1 and SGalase2 are predicted to belong to the CAZy glycosyl hydrolase family GH 43 based on activity, sequence homology and phylogenetic analysis. The K-m and V-max of the native exo-beta-(1 -> 3)-D-galactanase for de-arabinosylated gum arabic (dGA) were 19 mg/ml and 9.7 mu mol D-Gal/ min/mg protein, respectively. The activity of these enzymes is well suited for the study of type II galactan structures and provides an important tool for the investigation of the biological role of AGPs in plants. De-arabinosylated gum arabic (dGA) was used as a model to investigate the use of these enzymes in defining type II galactan structure. Exhaustive hydrolysis of dGA resulted in a limited number of oligosaccharide products with a trisaccharide of Gal(2)GlcA(1) predominating. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ling, Naomi X. -Y.; Lee, Joanne; Ellis, Miriam; Liao, Ming-Long; Mau, Shaio-Lim; Bacic, Antony; Pettolino, Filomena A.] Univ Melbourne, Plant Cell Biol Res Ctr, Sch Bot, Melbourne, Vic 3010, Australia.
[Bacic, Antony] Univ Melbourne, ARC Ctr Excellence Plant Cell Walls, Sch Bot, Melbourne, Vic 3010, Australia.
[Guest, David] Univ Sydney, Fac Agr Food & Nat Resources, Eveleigh, NSW 2015, Australia.
[Janssen, Peter H.] AgResearch Ltd, Grasslands Res Ctr, Palmerston North 4442, New Zealand.
[Kovac, Pavol] Inst Diabet & Digest & Kidney Dis NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Pettolino, FA (reprint author), CSIRO Plant Ind, Black Mt Labs, Canberra, ACT 2601, Australia.
EM Filomena.Pettolino@csiro.au
RI Pettolino, Filomena/I-1493-2012; Guest, David/A-9481-2011;
OI Guest, David/0000-0002-4138-5635; Lee, Joanne/0000-0003-0333-3524
FU Co-operative Research Centre (CRC) for Bioproducts; Melbourne
International Research Scholarship (MIRS)
FX Microbial isolation work for the source of enzyme was carried out by
Kathryn Davis (Department of Microbiology and Immunology, University of
Melbourne). All sample-derived tryptic peptide analyses were run by Dr.
Siria Natera, and the MS and MS/MS data were interpreted and de novo
sequenced by Ms. Kristina Ford and Dr. Siria Natera (School of Botany,
The University of Melbourne). This project was supported by funds from
the Co-operative Research Centre (CRC) for Bioproducts and Melbourne
International Research Scholarship (MIRS).
NR 69
TC 9
Z9 9
U1 1
U2 19
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 MAY 1
PY 2012
VL 352
BP 70
EP 81
DI 10.1016/j.carres.2012.02.033
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 925RF
UT WOS:000302778000009
PM 22464224
ER
PT J
AU Solier, S
Zhang, YW
Ballestrero, A
Pommier, Y
Zoppoli, G
AF Solier, S.
Zhang, Y. -W.
Ballestrero, A.
Pommier, Y.
Zoppoli, G.
TI DNA Damage Response Pathways and Cell Cycle Checkpoints in Colorectal
Cancer: Current Concepts and Future Perspectives for Targeted Treatment
SO CURRENT CANCER DRUG TARGETS
LA English
DT Review
DE Colorectal cancer; Chk2; cell cycle; DNA damage response; irinotecan;
oxaliplatin
ID GROWTH-FACTOR RECEPTOR; PEUTZ-JEGHERS-SYNDROME; PLATINUM-BASED
CHEMOTHERAPY; TOPOISOMERASE-I INHIBITORS; CHEK2 1100DELC MUTATION;
ANTICANCER DRUG SCREEN; HUMAN COLON-CANCER; POLY(ADP-RIBOSE) POLYMERASE;
MITOTIC CHECKPOINT; LUNG-CANCER
AB Although several drugs have been designed in the last few years to target specific key pathways and functions in colorectal cancer (CRC), the backbone of CRC treatment is still made up of compounds which rely on DNA damage to accomplish their role. DNA damage response (DDR) and checkpoint pathways are intertwined signaling networks that arrest cell cycle, recognize and repair genetic mistakes which arise during DNA replication and transcription, as well as through the exposure to chemical and physical agents that interact with nucleic acids. The good but highly variable activity of DNA damaging agents in the treatment of CRC suggests that intrinsic alterations in DDR pathways and cell cycle checkpoints may contribute differentially to the way cancer cells react to DNA damage. In the present review, our aim is to depict the recent advances in understanding the molecular basis of the activity of DNA damaging agents used for the treatment of CRC. We focus on the known and potential drug targets that are part of these complex and intertwined pathways. We describe the potential role of the checkpoints in CRC, and how their pharmacological manipulation could lead to chemopotentiation or synergism with currently used drugs. Novel therapeutic agents playing a role in DDR and checkpoint inhibition are assessed. We discuss the possible rationale for combining PARP inhibition with DNA damaging agents, and we address the link between DDR and EGFR pathways in CRC.
C1 [Solier, S.; Zhang, Y. -W.; Pommier, Y.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ballestrero, A.; Zoppoli, G.] Univ Genoa, Dept Internal Med DiMI, Genoa, Italy.
RP Zoppoli, G (reprint author), Avancorpo II Piano DiMI, Room 223,Vle Benedetto XV 6, I-16132 Genoa, Italy.
EM gabriele.zoppoli@unige.it
RI ZHANG, YONGWEI/E-6252-2012; Zoppoli, Gabriele/B-6935-2016
OI Zoppoli, Gabriele/0000-0003-3890-5588
FU AIRC [10570]
FX This work was in part supported by an AIRC "My First AIRC Grant", ID No.
10570.
NR 196
TC 10
Z9 12
U1 2
U2 17
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0096
J9 CURR CANCER DRUG TAR
JI Curr. Cancer Drug Targets
PD MAY
PY 2012
VL 12
IS 4
BP 356
EP 371
PG 16
WC Oncology
SC Oncology
GA 927ZZ
UT WOS:000302950600006
PM 22385513
ER
PT J
AU Andersen, JB
Thorgeirsson, SS
AF Andersen, Jesper B.
Thorgeirsson, Snorri S.
TI Genetic profiling of intrahepatic cholangiocarcinoma
SO CURRENT OPINION IN GASTROENTEROLOGY
LA English
DT Review
DE cholangiocarcinoma; extrahepatic cholangiocarcinoma; intrahepatic
cholangiocarcinoma
ID COMPARATIVE GENOMIC HYBRIDIZATION; PRIMARY SCLEROSING CHOLANGITIS;
MALIGNANT HUMAN CHOLANGIOCYTES; POTENTIAL THERAPEUTIC TARGETS;
CPG-ISLAND METHYLATION; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE;
K-RAS MUTATIONS; BILIARY-TRACT; EPIGENETIC ALTERATIONS
AB Purpose of review
Intrahepatic cholangiocarcinoma (ICC) is a treatment-refractory disease with a dismal outcome. Limited success in the clinical management and a persistent increase in the incidence world-wide have made ICC one of the most lethal and fastest growing malignancies. However, recent advancements in genome-wide technologies combined with the application of integrative multidimensional analytical approaches have begun to provide both detailed insight into the underlying biological traits of ICC and identified new therapeutic opportunities.
Recent findings
In comparison with other cancers, genomic studies of ICC have been limited. We and others have recently procured large cohorts of ICC patients intended for genome-wide analyses. In our study, samples from ICC patients were obtained from three cancer centers and subjected to integrated genetic and genomic analyses. We provided new insights into both pathogenesis and optimal treatment options demonstrating the presence of unique subclasses of patients, based partly on KRAS mutations and increased levels of receptor tyrosine kinase signaling. The group of patients with the worst prognosis was characterized by transcriptional enrichment of genes regulating inflammation and proteasome activities, suggesting a combination of tyrosine kinase inhibitors and anti-inflammatory drugs as a new therapeutic option for these patients.
Summary
We have critically examined the progress in genome-wide studies of ICC including genetic profiling, transcriptomics, and epigenomics. Current limitations in applying these technologies to archival samples and the insufficient access to fresh-frozen material are partly the cause of the delayed implementation of the omics-based investigations of ICC compared to other hepatobiliary diseases. Thus, selected candidate single-gene studies will also be discussed.
C1 [Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, CCR, NIH, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Center for Cancer Research, NCI, NIH
FX No potential conflict of interest related to this study was reported.
The study was supported by the Intramural Research Program of the Center
for Cancer Research, NCI, NIH.
NR 65
TC 39
Z9 41
U1 0
U2 7
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 MAY
PY 2012
VL 28
IS 3
BP 266
EP 272
DI 10.1097/MOG.0b013e3283523c7e
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 927YE
UT WOS:000302945700014
PM 22395571
ER
PT J
AU Metenou, S
Babu, S
Nutman, TB
AF Metenou, Simon
Babu, Subash
Nutman, Thomas B.
TI Impact of filarial infections on coincident intracellular pathogens:
Mycobacterium tuberculosis and Plasmodium falciparum
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE filarial infections; immunomodulation; malaria; tuberculosis
ID PATENT LYMPHATIC FILARIASIS; PARASITE-SPECIFIC ANERGY; T-CELLS;
IMMUNE-RESPONSES; BANCROFTIAN FILARIASIS; DENDRITIC CELLS; ANTIGEN
PRESENTATION; STAGE MALARIA; IMMUNOLOGICAL RESPONSIVENESS;
WUCHERERIA-BANCROFTI
AB Purpose of review
To examine the consequences of the immune modulation seen in chronic filarial infection on responses to intracellular pathogens (and their antigens) that are often co-endemic with filarial infections, namely Plasmodium and Mycobacterium tuberculosis.
Recent findings
Much of the recent data on filaria/mycobacteria or filaria/Plasmodium co-infection has focused on the modulation of mycobacteria-specific or malaria-specific responses by chronic filarial infection. As such, filarial infections very clearly alter the magnitude and quality of the mycobacteria-specific or malaria-specific cytokine responses, responses that have been typically associated with control of these intracellular pathogens.
Summary
Although phylogenetically distinct, mycobacteria and Plasmodium spp. often share the same geographical niche with filarial infections. The complex interplay between filarial parasites that are associated with immunomodulation and those microbial pathogens that require a proinflammatory or unmodulated response for their control is easily demonstrable ex vivo, but whether this interplay affects disease outcome in tuberculosis or malaria remains an open question.
C1 [Metenou, Simon; Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Babu, Subash] ICER, NIRT, Madras, Tamil Nadu, India.
RP Nutman, TB (reprint author), Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
RI Metenou, Simon/C-1101-2013
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; National Institutes of Health, USA
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, and National Institutes of Health, USA.
NR 68
TC 23
Z9 23
U1 0
U2 10
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 MAY
PY 2012
VL 7
IS 3
BP 231
EP 238
DI 10.1097/COH.0b013e3283522c3d
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 925TA
UT WOS:000302783200005
PM 22418448
ER
PT J
AU Nandy, K
AF Nandy, Kaustav
TI Interactive segmentation and tracking in optical microscopic images
SO CYTOMETRY PART A
LA English
DT Editorial Material
DE interactive segmentation; tissue segmentation; cell tracking; seeded
watershed algorithm; optical microscopy
ID CELLS
C1 NCI, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Adv Technol Program, Frederick, MD 21702 USA.
RP Nandy, K (reprint author), NCI, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Adv Technol Program, POB B, Frederick, MD 21702 USA.
EM nandyk@mail.nih.gov
FU PHS HHS [HHSN261200800001E]
NR 12
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD MAY
PY 2012
VL 81A
IS 5
BP 357
EP 359
DI 10.1002/cyto.a.22055
PG 3
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 928SN
UT WOS:000303004300003
PM 22499415
ER
PT J
AU Foulds, KE
Donaldson, M
Roederer, M
AF Foulds, Kathryn E.
Donaldson, Mitzi
Roederer, Mario
TI OMIP-005: Quality and phenotype of antigen-responsive rhesus macaque T
cells
SO CYTOMETRY PART A
LA English
DT Article
DE intracellular cytokine; T cells; vaccines; HIV
C1 [Foulds, Kathryn E.; Donaldson, Mitzi; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Foulds, KE (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5507, Bethesda, MD 20892 USA.
EM FouldsK@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH;
Collaboration for AIDS Vaccine Discovery (CAVD) [38650]
FX Grant sponsor: National Institute of Allergy and Infectious Diseases,
NIH (Intramural Research Program); Grant sponsor: Collaboration for AIDS
Vaccine Discovery (CAVD) award; Grant number: #38650;
NR 4
TC 8
Z9 8
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD MAY
PY 2012
VL 81A
IS 5
BP 360
EP 361
DI 10.1002/cyto.a.22008
PG 2
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 928SN
UT WOS:000303004300004
PM 22438313
ER
PT J
AU Lamoreaux, L
Koup, RA
Roederer, M
AF Lamoreaux, Laurie
Koup, Richard A.
Roederer, Mario
TI OMIP-009: Characterization of antigen-specific human T-cells
SO CYTOMETRY PART A
LA English
DT Article
DE intracellular cytokines; vaccines; T cells; HIV
C1 [Lamoreaux, Laurie; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Lamoreaux, L (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3613, Bethesda, MD 20892 USA.
EM llamorea@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH;
Collaboration for AIDS Vaccine Discovery (CAVD) [38650]
FX The authors thank Ellen Turk and Jennifer Fischer for assistance in
developing and optimizing the panel; Pratip Chattopadhyay and Joanne Yu
for advice in optimizing the multicolor panel and characterizing
reagents; and Steven Perfetto and Richard Nguyen for expert flow
cytometry advice. This work was supported by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
NIH, and the Collaboration for AIDS Vaccine Discovery (CAVD) award
#38650.
NR 3
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD MAY
PY 2012
VL 81A
IS 5
BP 362
EP 363
DI 10.1002/cyto.a.22042
PG 2
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 928SN
UT WOS:000303004300005
PM 22438322
ER
PT J
AU Orlov, NV
Weeraratna, AT
Hewitt, SM
Coletta, CE
Delaney, JD
Eckley, D
Shamir, L
Goldberg, IG
AF Orlov, Nikita V.
Weeraratna, Ashani T.
Hewitt, Stephen M.
Coletta, Christopher E.
Delaney, John D.
Mark Eckley, D.
Shamir, Lior
Goldberg, Ilya G.
TI Automatic detection of melanoma progression by histological analysis of
secondary sites
SO CYTOMETRY PART A
LA English
DT Article
DE melanoma progression; histopathological image analysis; nonparametric
image analysis; H&E data; tissue classification
ID FEATURE-SELECTION; CANCER DIAGNOSIS; IMAGE-ANALYSIS; CLASSIFICATION;
RECOGNITION; METASTASIS; PATHOLOGY; LYMPHOMA; FEATURES; TISSUES
AB We present results from machine classification of melanoma biopsies sectioned and stained with hematoxylin/eosin (H&E) on tissue microarrays (TMA). The four stages of melanoma progression were represented by seven tissue types, including benign nevus, primary tumors with radial and vertical growth patterns (stage I) and four secondary metastatic tumors: subcutaneous (stage II), lymph node (stage III), gastrointestinal and soft tissue (stage IV). Our experiment setup comprised 14,208 image samples based on 164 TMA cores. In our experiments, we constructed an HE color space by digitally deconvolving the RGB images into separate H (hematoxylin) and E (eosin) channels. We also compared three different classifiers: Weighted Neighbor Distance (WND), Radial Basis Functions (RBF), and k-Nearest Neighbors (kNN). We found that the HE color space consistently outperformed other color spaces with all three classifiers, while the different classifiers did not have as large of an effect on accuracy. This showed that a more physiologically relevant representation of color can have a larger effect on correct image interpretation than downstream processing steps. We were able to correctly classify individual fields of view with an average of 96% accuracy when randomly splitting the dataset into training and test fields. We also obtained a classification accuracy of 100% when testing entire cores that were not previously used in training (four random trials with one test core for each of 7 classes, 28 tests total). Because each core corresponded to a different patient, this test more closely mimics a clinically relevant setting where new patients are evaluated based on training with previous cases. The analysis method used in this study contains no parameters or adjustments that are specific to melanoma morphology, suggesting it can be used for analyzing other tissues and phenotypes, as well as potentially different image modalities and contrast techniques. Published 2012 Wiley Periodicals, Inc.
C1 [Orlov, Nikita V.; Coletta, Christopher E.; Delaney, John D.; Mark Eckley, D.; Goldberg, Ilya G.] NIA, NIH, Genet Lab, Baltimore, MD 21224 USA.
[Weeraratna, Ashani T.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA.
[Hewitt, Stephen M.] NCI, NIH, Tissue Array Res Program, Adv Technol Ctr, Bethesda, MD 20892 USA.
[Shamir, Lior] Lawrence Tech Univ, Dept Comp Sci, Southfield, MI USA.
RP Orlov, NV (reprint author), 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA.
EM norlov@nih.gov
RI Goldberg, Ilya/H-5307-2011;
OI Goldberg, Ilya/0000-0001-8514-6110; Hewitt, Stephen/0000-0001-8283-1788
FU NIH, National Institute on Aging [Z01: AG000685-02]
FX Grant sponsor: Intramural Research Program of the NIH, National
Institute on Aging; Grant number: Z01: AG000685-02
NR 53
TC 3
Z9 3
U1 0
U2 6
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 MAY
PY 2012
VL 81A
IS 5
BP 364
EP 373
DI 10.1002/cyto.a.22044
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 928SN
UT WOS:000303004300006
PM 22467531
ER
PT J
AU Tembhare, P
Yuan, CM
Xi, LQ
Marti, G
Raffeld, M
Stetler-Stevenson, M
AF Tembhare, Prashant
Yuan, Constance M.
Xi, Liqiang
Marti, Gerald
Raffeld, Mark
Stetler-Stevenson, Maryalice
TI Case study interpretation-Portland: Case 1
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
ID B-CELL LYMPHOCYTOSIS; LEUKEMIA; BIOLOGY; CLONES; MBL
C1 [Tembhare, Prashant] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Marti, Gerald] US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA.
RP Tembhare, P (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA.
EM tembharep@mail.nih.gov
FU NIH, NCI
FX Grant sponsor: Intramural Research Program of the NIH, NCI.
NR 8
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD MAY
PY 2012
VL 82B
IS 3
BP 177
EP 179
DI 10.1002/cyto.b.21012
PG 3
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 927VA
UT WOS:000302937200010
PM 22431420
ER
PT J
AU Blackburn, J
Ohazama, A
Kawasaki, K
Otsuka-Tanaka, Y
Liu, BG
Honda, K
Rountree, RB
Hu, YL
Kawasaki, M
Birchmeier, W
Schmidt-Ullrich, R
Kinoshita, A
Schutte, BC
Hammond, NL
Dixon, MJ
Sharpe, PT
AF Blackburn, James
Ohazama, Atsushi
Kawasaki, Katsushige
Otsuka-Tanaka, Yoko
Liu, Bigang
Honda, Kenya
Rountree, Ryan B.
Hu, Yinling
Kawasaki, Maiko
Birchmeier, Walter
Schmidt-Ullrich, Ruth
Kinoshita, Akira
Schutte, Brian C.
Hammond, Nigel L.
Dixon, Michael J.
Sharpe, Paul T.
TI The role of Irf6 in tooth epithelial invagination
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Ikk alpha; Irf6; Wnt; Incisor; Invagination; Epithelium; Tooth
development
ID NF-KAPPA-B; DER-WOUDE-SYNDROME; POPLITEAL PTERYGIUM SYNDROME;
GAMMA-SECRETASE INHIBITORS; IKK-ALPHA; TRANSCRIPTION FACTORS; GENE
INDUCTION; INTERFERON RESPONSES; SIGNALING PATHWAYS; TMJ DEVELOPMENT
AB Thickening and the subsequent invagination of the epithelium are an important initial step in Ectodermal organ development. Ikk alpha has been shown to play a critical role in controlling epithelial growth, since Ikk alpha mutant mice show protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium rather than invagination. We show here that mutation of the Interferon regulatory factor (11) family, Irf6 also results in evagination of incisor epithelium. In common with Ikk alpha mutants, Irf6 mutant evagination occurs in a NF-kappa B-independent manner and shows the same molecular changes as those in Ikk alpha mutants. Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk alpha and Irf6 mutant embryos. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Blackburn, James; Ohazama, Atsushi; Kawasaki, Katsushige; Otsuka-Tanaka, Yoko; Kawasaki, Maiko; Sharpe, Paul T.] Kings Coll London, Inst Dent, Dept Craniofacial Dev, London SE1 9RT, England.
[Blackburn, James; Ohazama, Atsushi; Kawasaki, Katsushige; Otsuka-Tanaka, Yoko; Kawasaki, Maiko; Sharpe, Paul T.] Kings Coll London, Inst Dent, Comprehens Biomed Res Ctr, London SE1 9RT, England.
[Liu, Bigang] Univ Texas MD Anderson Canc Ctr, Smithville, TX USA.
[Honda, Kenya] Univ Tokyo, Grad Sch Med, Dept Immunol, Tokyo, Japan.
[Honda, Kenya] Univ Tokyo, Fac Med, Tokyo 113, Japan.
[Rountree, Ryan B.] Amgen Inc, Dept Oncol, Seattle, WA USA.
[Hu, Yinling] NCI, Expt Immunol Lab, Inflammat & Tumorigenesis Sect, Frederick, MD 21701 USA.
[Kawasaki, Maiko] Niigata Univ, Grad Sch Med & Dent Sci, Dept Oral Hlth Sci, Course Oral Life Sci,Div Bioprosthodont, Niigata, Japan.
[Birchmeier, Walter] Max Delbruck Ctr Mol Med, Dept Canc Res, D-13092 Berlin, Germany.
[Schmidt-Ullrich, Ruth] Max Delbruck Ctr Mol Med, Dept Signal Transduct Tumor Cells, D-13092 Berlin, Germany.
[Kinoshita, Akira] Nagasaki Univ, Dept Human Genet, Grad Sch Biomed Sci, Nagasaki 852, Japan.
[Kinoshita, Akira; Schutte, Brian C.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
[Hammond, Nigel L.; Dixon, Michael J.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Life Sci, Manchester, Lancs, England.
[Hammond, Nigel L.; Dixon, Michael J.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Sch Dent, Manchester, Lancs, England.
[Ohazama, Atsushi] Showa Univ, Sch Dent, Dept Periodontol, Ohta Ku, Tokyo 142, Japan.
RP Ohazama, A (reprint author), Kings Coll London, Inst Dent, Dept Craniofacial Dev, Floor 27,Guys Tower, London SE1 9RT, England.
EM Atsushi.2.Ohazama@kcl.ac.uk; paul.sharpe@kcl.ac.uk
FU MRC; Ministry of Education, Culture, Sports, Science and Technology of
Japan [16592080]; JSPS; Nihon University; NIH [DE13513]
FX We would like to thank Amgen for Rip4 mutant mice, Ken Brady for TEM
analysis, Dr. Koyama for HistoneH4C plasmids (Ochiai et al., 2010;
Yasuda et al., 2010) and Tony Brain for SEM analysis. This work was
supported by the MRC and was partly funded by grants from the Ministry
of Education, Culture, Sports, Science and Technology of Japan (No.
16592080). K.K. is supported by JSPS International Program for Young
Researcher Overseas Visits. Y.O.-K. is supported by Nihon University.
S.C.A. and A.K. were supported by NIH DE13513.
NR 77
TC 10
Z9 10
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAY 1
PY 2012
VL 365
IS 1
BP 61
EP 70
DI 10.1016/j.ydbio.2012.02.009
PG 10
WC Developmental Biology
SC Developmental Biology
GA 928ZG
UT WOS:000303030400006
PM 22366192
ER
PT J
AU English, MA
Lei, L
Blake, T
Wincovitch, SM
Sood, R
Azuma, M
Hickstein, D
Liu, PP
AF English, Milton A.
Lei, Lin
Blake, Trevor
Wincovitch, Stephen M., Sr.
Sood, Raman
Azuma, Mizuki
Hickstein, Dennis
Liu, P. Paul
TI Incomplete splicing, cell division defects, and hematopoietic blockage
in dhx8 mutant zebrafish
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE dhx8 mutant zebrafish; hematopoiesis; cell division defects
ID HELICASE-LIKE PROTEIN; MESSENGER-RNA; DEFINITIVE HEMATOPOIESIS;
TRANSGENIC ZEBRAFISH; ENDOTHELIAL LINEAGES; FACTOR PRP22; EXPRESSION;
EMBRYO; GENE; SPLICEOSOME
AB Background: Vertebrate hematopoiesis is a complex developmental process that is controlled by genes in diverse pathways. To identify novel genes involved in early hematopoiesis, we conducted an ENU (N-ethyl-N-nitrosourea) mutagenesis screen in zebrafish. The mummy (mmy) line was investigated because of its multiple hematopoietic defects. Results: Homozygous mmy embryos lacked circulating blood cell types and were dead by 30 hr post-fertilization (hpf). The mmy mutants did not express myeloid markers and had significantly decreased expression of progenitor and erythroid markers in primitive hematopoiesis. Through positional cloning, we identified a truncation mutation in dhx8 in the mmy fish. dhx8 is the zebrafish ortholog of the yeast splicing factor prp22, which is a DEAH-box RNA helicase. mmy mutants had splicing defects in many genes, including several hematopoietic genes. mmy embryos also showed cell division defects as characterized by disorganized mitotic spindles and formation of multiple spindle poles in mitotic cells. These cell division defects were confirmed by DHX8 knockdown in HeLa cells. Conclusions: Together, our results confirm that dhx8 is involved in mRNA splicing and suggest that it is also important for cell division during mitosis. This is the first vertebrate model for dhx8, whose function is essential for primitive hematopoiesis in developing embryos. Developmental Dynamics 241:879889, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [English, Milton A.; Lei, Lin; Blake, Trevor; Wincovitch, Stephen M., Sr.; Sood, Raman; Liu, P. Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Azuma, Mizuki; Hickstein, Dennis; Liu, P. Paul] NCI, NIH, Bethesda, MD 20892 USA.
RP Liu, PP (reprint author), NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
EM pliu@mail.nih.gov
RI Liu, Paul/A-7976-2012
OI Liu, Paul/0000-0002-6779-025X
FU National Human Genome Research Institute; National Cancer Institute,
NIH; UNCF/Merck
FX Grant sponsor: Intramural Research Programs of the National Human Genome
Research Institute and National Cancer Institute, NIH.; This study was
supported by the Intramural Research Programs of the National Human
Genome Research Institute and National Cancer Institute, NIH. M.A.E. was
supported by a fellowship from UNCF/Merck. We thank Christine and
Bernard Thisse for in situ hybridization of dhx8 during embryonic
development 9Thisse and Thisse, 2008), Julia Fekecs for help with
graphics illustrations, and Abdel Elkahloun and Niraj S. Trivedi for
performing the microarray hybridizations and analysis.
NR 58
TC 9
Z9 9
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD MAY
PY 2012
VL 241
IS 5
BP 879
EP 889
DI 10.1002/dvdy.23774
PG 11
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 926VY
UT WOS:000302861200005
PM 22411201
ER
PT J
AU Mitterberger, MC
Kim, G
Rostek, U
Levine, RL
Zwerschke, W
AF Mitterberger, Maria C.
Kim, Geumsoo
Rostek, Ursula
Levine, Rodney L.
Zwerschke, Werner
TI Carbonic anhydrase III regulates peroxisome proliferator-activated
receptor-gamma 2
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Adipocyte; Adipogenesis; Aging; Caloric restriction; Carbonic anhydrase
Ill; Oxidative stress; Preadipocyte; PPAR gamma 2; FABP4
ID OXIDATIVE STRESS; GENE-EXPRESSION; S-THIOLATION; PPAR-GAMMA; ADIPOCYTE
DIFFERENTIATION; PHOSPHATASE-ACTIVITY; PROTEIN SULFHYDRYLS;
INSULIN-RESISTANCE; SKELETAL-MUSCLE; ENERGY-BALANCE
AB Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO2 have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII(-/-) MEFs compared with CAIII(+/+) cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) and CCAAT/enhancer binding protein-alpha. We found a considerable (approximately 1000-fold) increase in the PPAR gamma 2 expression in the CAIII(-/-) MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPAR gamma 2 and FABP4. When both CAIII and PPAR gamma 2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPAR gamma 2 gene expression. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Mitterberger, Maria C.; Rostek, Ursula; Zwerschke, Werner] Austrian Acad Sci, Inst Biomed Aging Res, Cell Metab & Differentiat Res Grp, A-6020 Innsbruck, Austria.
[Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Zwerschke, W (reprint author), Austrian Acad Sci, Inst Biomed Aging Res, Cell Metab & Differentiat Res Grp, Rennweg 10, A-6020 Innsbruck, Austria.
EM werner.zwerschke@oeaw.ac.at
RI Levine, Rodney/D-9885-2011
FU Austrian Academy of Sciences; National Heart, Lung, and Blood Institute
FX We are grateful to D. Trono (Lausanne, Switzerland) for the plasmid
pMD2.G and psPAX2. This work was supported by funding from the Austrian
Academy of Sciences (M.C.M., U.R., W.Z.) and by the Intramural Research
Program of the National Heart, Lung, and Blood Institute (G.K., R.L.L).
NR 49
TC 15
Z9 15
U1 0
U2 4
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 MAY 1
PY 2012
VL 318
IS 8
BP 877
EP 886
DI 10.1016/j.yexcr.2012.02.011
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 925MR
UT WOS:000302765800002
PM 22507175
ER
PT J
AU Simon, SL
Coleman, CN
Noska, MA
Bowman, T
AF Simon, Steven L.
Coleman, C. Norman
Noska, Michael A.
Bowman, Thomas
TI RESPONSE OF THE US DEPARTMENT OF HEALTH AND HUMAN SERVICES IN PROTECTING
CIVILIAN AMERICANS IN JAPAN DURING THE FUKUSHIMA NUCLEAR CRISIS
SO HEALTH PHYSICS
LA English
DT Article
DE operational topics; emergency planning; exposure, radiation; radiation
safety; emergency response
AB Following the earthquake and tsunami in northern Japan on 11 March 2011 and the ensuing damage to the Fukushima Daiichi Nuclear Power Plant complex, a request by the U. S. Ambassador to Japan to the U. S. Department of Health and Human Services (DHHS) Assistant Secretary for Preparedness and Response (ASPR) resulted in deployment of a five-person team of subject matter experts to the U. S. Embassy. The primary purpose of the deployment was to provide the U. S. Embassy in Tokyo with guidance on health and medical issues related to potential radiation exposure of U. S. citizens in Japan, including employees of the U. S. Department of State at consulates in Japan and American citizens living in or visiting Japan. At the request of the Government of Japan (GOJ), the deployed health team also assisted Japanese experts in their public health response to the radiation incident. Over a 3-wk period in Japan and continuing for weeks after their return to the U. S., the team provided expertise in the areas of medical and radiation oncology; health physics; assessment of radiation dose and cancer risk, particularly to U. S. citizens living in Tokyo and the surrounding areas; food and water contamination and the acceptable limits; countermeasures to exposure such as potassium iodide (KI); the use of KI and an offered donation from the United States;, evacuation and re-entry issues; and health/emergency-related communication strategies. This paper describes the various strategies used and observations made by the DHHS team during the first 2 mo after the Fukushima crisis began. Health Phys. 102(5):570-579; 2012
C1 [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Coleman, C. Norman] Dept Hlth & Human Serv, Off Preparedness & Emergency Operat, Washington, DC USA.
[Noska, Michael A.] US FDA, Silver Spring, MD USA.
[Bowman, Thomas] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU DHHS; NIH; NCI; NCI Division of Cancer Epidemiology
FX The authors are appreciative of support from the DHHS and individual
agencies they represent and especially Dr. Nicole Lurie, the DHHS
Assistant Secretary for Preparedness and Response. In addition, the
authors are appreciative of the support from the Directors of the NIH,
NCI, and the NCI Division of Cancer Epidemiology, the FDA Office of
International Programs, and the FDA Office of Crisis Management for
their logistic support. The authors gratefully acknowledge the
dedication and expertise of a team member, Jana Telfer of the CDC, in
the area of risk communications.
NR 24
TC 3
Z9 3
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD MAY
PY 2012
VL 102
IS 5
BP 570
EP 579
DI 10.1097/HP.0b013e31824c79e5
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 925VG
UT WOS:000302789300014
ER
PT J
AU Miller, TL
Borkowsky, W
DiMeglio, LA
Dooley, L
Geffner, ME
Hazra, R
McFarland, EJ
Mendez, AJ
Patel, K
Siberry, GK
Van Dyke, RB
Worrell, CJ
Jacobson, DL
AF Miller, T. L.
Borkowsky, W.
DiMeglio, L. A.
Dooley, L.
Geffner, M. E.
Hazra, R.
McFarland, E. J.
Mendez, A. J.
Patel, K.
Siberry, G. K.
Van Dyke, R. B.
Worrell, C. J.
Jacobson, D. L.
CA PHACS
TI Metabolic abnormalities and viral replication are associated with
biomarkers of vascular dysfunction in HIV-infected children
SO HIV MEDICINE
LA English
DT Article
DE children; HIV; AIDS; vascular dysfunction; cardiovascular risk factors;
biomarkers
ID INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; HUMAN IMMUNODEFICIENCY
VIRUS-1; BETA-CELL FUNCTION; ANTIRETROVIRAL THERAPY;
CARDIOVASCULAR-DISEASE; RISK-FACTORS; ENDOTHELIAL ACTIVATION;
MYOCARDIAL-INFARCTION; LONGITUDINAL CHANGES
AB Objectives
HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/ AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers.
Methods
A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded.
Results
The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P-and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM).
Conclusions
HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.
C1 [Miller, T. L.] Univ Miami, Miller Sch Med, Div Pediat Clin Res, Dept Pediat, Miami, FL 33101 USA.
[Borkowsky, W.] NYU, Sch Med, New York, NY USA.
[DiMeglio, L. A.] Indiana Univ Sch Med, Sect Pediat Endocrinol & Diabetol, Dept Pediat, Indianapolis, IN USA.
[Dooley, L.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Geffner, M. E.] USC, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA USA.
[Hazra, R.; Siberry, G. K.; Worrell, C. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[McFarland, E. J.] Univ Colorado, Dept Pediat, Denver Sch Med, Denver, CO 80202 USA.
[Mendez, A. J.] Univ Miami, Miller Sch Med, Diabet Res Inst, Dept Med,Div Endocrinol Diabet & Metab, Miami, FL 33101 USA.
[Patel, K.; Jacobson, D. L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Dept Epidemiol, Boston, MA 02115 USA.
[Van Dyke, R. B.] Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA.
RP Miller, TL (reprint author), Univ Miami, Batchelor Childrens Res Inst, Miller Sch Med, Div Pediat Clin Res,Dept Pediat D820, POB 016820, Miami, FL 33101 USA.
EM tracie.miller@miami.edu
OI DiMeglio, Linda/0000-0002-8033-6078
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Deafness and Other Communication Disorders;
National Heart Lung and Blood Institute; National Institute of
Neurological Disorders and Stroke; National Institute on Alcohol Abuse
and Alcoholism [U01 HD052102-04]; Tulane University School of Medicine
[U01 HD052104-01]; NIH/NCRR Colorado CTSI [UL1 RR025780]
FX The study was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development with co-funding from the National
Institute of Allergy and Infectious Diseases, the National Institute on
Drug Abuse, the National Institute of Mental Health, the National
Institute of Deafness and Other Communication Disorders, the National
Heart Lung and Blood Institute, the National Institute of Neurological
Disorders and Stroke, and the National Institute on Alcohol Abuse and
Alcoholism, through cooperative agreements with the Harvard University
School of Public Health (U01 HD052102-04) (Principal Investigator:
George R. Seage, III; Project Director: Julie Alperen) and the Tulane
University School of Medicine (U01 HD052104-01) (Principal Investigator:
Russell B. Van Dyke; Co-Principal Investigator: Kenneth Rich; Project
Director: Patrick Davis). Data management services were provided by
Frontier Science and Technology Research Foundation (Principal
Investigator: Suzanne Siminski), and regulatory services and logistical
support were provided by Westat, Inc. (Principal Investigator: Mercy
Swatson). This study was supported by NIH/NCRR Colorado CTSI Grant
Number UL1 RR025780. Its contents are the authors' sole responsibility.
NR 57
TC 26
Z9 27
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-2662
J9 HIV MED
JI HIV Med.
PD MAY
PY 2012
VL 13
IS 5
BP 264
EP 275
DI 10.1111/j.1468-1293.2011.00970.x
PG 12
WC Infectious Diseases
SC Infectious Diseases
GA 923LD
UT WOS:000302619900002
PM 22136114
ER
PT J
AU Mills, JL
Carter, TC
Kay, DM
Browne, ML
Brody, LC
Liu, AY
Romitti, PA
Caggana, M
Druschel, CM
AF Mills, James L.
Carter, Tonia C.
Kay, Denise M.
Browne, Marilyn L.
Brody, Lawrence C.
Liu, Aiyi
Romitti, Paul A.
Caggana, Michele
Druschel, Charlotte M.
TI Folate and vitamin B12-related genes and risk for omphalocele
SO HUMAN GENETICS
LA English
DT Article
ID NEURAL-TUBE DEFECTS; NEW-YORK-STATE; BIRTH-DEFECTS; PREVENTION;
GASTROSCHISIS; POLYMORPHISMS; SURVEILLANCE; METABOLISM; IMPACT
AB Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported to reduce omphalocele rates. Genetic factors are etiologically important in omphalocele as well; our pilot study showed a relationship with the folate metabolic enzyme gene methylenetetrahydrofolate reductase (MTHFR). We studied 169 non-aneuploid omphalocele cases and 761 unaffected, matched controls from all New York State births occurring between 1998 and 2005 to look for associations with single nucleotide polymorphisms (SNPs) known to be important in folate, vitamin B12, or choline metabolism. In the total study population, variants in the transcobalamin receptor gene (TCblR), rs2232775 (p.Q8R), and the MTHFR gene, rs1801131 (c.1298A > C), were significantly associated with omphalocele. In African-Americans, significant associations were found with SNPs in genes for the vitamin B12 transporter (TCN2) and the vitamin B12 receptor (TCblR). A SNP in the homocysteine-related gene, betaine-homocysteine S-methyltransferase (BHMT), rs3733890 (p.R239Q), was significantly associated with omphalocele in both African-Americans and Asians. Only the TCblR association in the total population remained statistically significant if Bonferroni correction was applied. The finding that transcobalamin receptor (TCblR) and transporter (TCN2) SNPs and a BHMT SNP were associated with omphalocele suggests that disruption of methylation reactions, in which folate, vitamin B12, and homocysteine play critical parts, may be a risk factor for omphalocele. Our data, if confirmed, suggest that supplements containing both folic acid and vitamin B12 may be beneficial in preventing omphaloceles.
C1 [Mills, James L.; Carter, Tonia C.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA.
[Kay, Denise M.; Caggana, Michele] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY 12201 USA.
[Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY 12180 USA.
[Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Dept Epidemiol & Biostat, Sch Publ Hlth, Rensselaer, NY 12144 USA.
[Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA 52242 USA.
RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
OI Kay, Denise/0000-0002-9928-2698; Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200703431C NICHD,
N01-DK-7-3431]
FX The authors thank April J. Atkins, Robert J. Sicko, and Emily C. McGrath
for laboratory and technical assistance. We are grateful to Sandra D.
Richardson for data management. This work was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health. Contract number: HHSN267200703431C NICHD No. N01-DK-7-3431.
NR 23
TC 8
Z9 8
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAY
PY 2012
VL 131
IS 5
BP 739
EP 746
DI 10.1007/s00439-011-1117-3
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 926FM
UT WOS:000302816700009
PM 22116453
ER
PT J
AU Judd, LL
Schettler, PJ
Akiskal, H
Coryell, W
Fawcett, J
Fiedorowicz, JG
Solomon, DA
Keller, MB
AF Judd, Lewis L.
Schettler, Pamela J.
Akiskal, Hagop
Coryell, William
Fawcett, Jan
Fiedorowicz, Jess G.
Solomon, David A.
Keller, Martin B.
TI Prevalence and clinical significance of subsyndromal manic symptoms,
including irritability and psychomotor agitation, during bipolar major
depressive episodes
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar; Major depressive episodes; Subsyndromal manic symptoms;
Irritability; Psychomotor agitation
ID BRANCH COLLABORATIVE PROGRAM; MIXED STATES; PSYCHOSOCIAL DISABILITY;
NATURAL-HISTORY; II DISORDERS; STEP-BD; VALIDATION; PSYCHOBIOLOGY;
DEFINITION; RECOVERY
AB Background: There is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of 'depressive mixed state.' This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined.
Methods: Bipolar (type I or II) patients with an MDE at intake (N =142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation.
Results: Subsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms.
Limitations: The findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment.
Conclusions: The presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Judd, Lewis L.; Akiskal, Hagop; Coryell, William; Fawcett, Jan; Solomon, David A.; Keller, Martin B.] NIMH, Collaborat Program Psychobiol Depress, Bethesda, MD USA.
[Judd, Lewis L.; Schettler, Pamela J.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Akiskal, Hagop] Vet Adm Hosp, San Diego, CA USA.
[Coryell, William; Fiedorowicz, Jess G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Fawcett, Jan] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA.
[Fiedorowicz, Jess G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Solomon, David A.] Brown Univ, Dept Psychiat & Human Behav, Sch Med, Providence, RI 02912 USA.
[Solomon, David A.] UpToDate Inc, Waltham, MA USA.
RP Judd, LL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM ljudd@ucsd.edu
FU National Institute of Mental (NIMH); Neurosearch
FX The initial funding source for the database utilized in this manuscript
was the National Institute of Mental (NIMH). The NIMH had no further
role in the design, analysis and interpretation of data; in the writing
of this report; and in the decision to submit the paper for
publication.; Drs. Judd, Akiskal, Coryell, and Fawcett declare that they
have no conflicts of interest or potential conflicts of interest. During
the past three years Dr. Schettler has provided statistical consulting
services to Brain Cell, Inc., Methylation Sciences, Novartis
BioVentures, and Clintara LLC. Dr. Fiedorowicz currently serves in an
unpaid capacity on a colleague's study that is supported by Neurosearch.
Dr. Solomon is an employee of UpToDate, Inc. During the past three years
Dr. Keller has served as a consultant to CENEREX, Forest Laboratories,
Medtronic, Organon, Pfizer, Sierra Neuropharmaceuticals, Shire, and
Wyeth; has served on the advisory boards for CENEREX, Forest
Laboratories, and Organon; and has conducted research using Pfizer and
Wyeth products.
NR 33
TC 37
Z9 37
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD MAY
PY 2012
VL 138
IS 3
BP 440
EP 448
DI 10.1016/j.jad.2011.12.046
PG 9
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 924AW
UT WOS:000302663900029
PM 22314261
ER
PT J
AU Oliveras-Rentas, RE
Kenworthy, L
Roberson, RB
Martin, A
Wallace, GL
AF Oliveras-Rentas, Rafael E.
Kenworthy, Lauren
Roberson, Richard B., III
Martin, Alex
Wallace, Gregory L.
TI WISC-IV Profile in High-Functioning Autism Spectrum Disorders: Impaired
Processing Speed is Associated with Increased Autism Communication
Symptoms and Decreased Adaptive Communication Abilities
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; IQ; Processing speed; Symptomatology; Adaptive behavior; ADHD;
Intelligence
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL
DISORDER; WECHSLER INTELLIGENCE SCALE; DIAGNOSTIC INTERVIEW; BEHAVIOR
SCALES; ADHD SYMPTOMS; CHILDREN; IQ; INDIVIDUALS; VINELAND
AB Changes in the Wechsler Intelligence Scales for Children-IV (WISC-IV) may affect the IQ profile characteristic of autism spectrum disorders (ASD). Moreover, the association of particular component cognitive abilities (unlike overall IQ) with symptomatology and adaptive functioning in ASD remains unclear. This archival study characterizes the WISC-IV IQ profile among 56 high-functioning (IQ > 70) children with ASD and correlates WISC-IV performance with ASD and ADHD symptomatology and adaptive functioning. The ASD WISC-IV profile included strengths on Matrix Reasoning and Similarities, weaknesses on Comprehension (which correlated negatively with social symptoms) and the subtests comprising the Processing Speed Index (Coding, Symbol Search). Processing speed task performance correlated negatively with communication symptoms and positively with communication abilities, indicating its importance to functional outcomes in ASD.
C1 [Roberson, Richard B., III; Martin, Alex; Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Oliveras-Rentas, Rafael E.; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA.
RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA.
EM gregwallace@mail.nih.gov
RI martin, alex/B-6176-2009;
OI Wallace, Gregory/0000-0003-0329-5054
FU Intramural NIH HHS [ZIA MH002920-03]
NR 56
TC 36
Z9 37
U1 8
U2 46
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD MAY
PY 2012
VL 42
IS 5
BP 655
EP 664
DI 10.1007/s10803-011-1289-7
PG 10
WC Psychology, Developmental
SC Psychology
GA 925OU
UT WOS:000302771500001
PM 21638108
ER
PT J
AU Cao, ZG
Zhang, H
Zhou, X
Han, XL
Ren, YS
Gao, T
Xiao, Y
de Crombrugghe, B
Somerman, MJ
Feng, JQ
AF Cao, Zhengguo
Zhang, Hua
Zhou, Xin
Han, Xianglong
Ren, Yinshi
Gao, Tian
Xiao, Yin
de Crombrugghe, Benoit
Somerman, Martha J.
Feng, Jian Q.
TI Genetic evidence for the vital function of osterix in cementogenesis
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE OSX; CEMENTUM; CEMENTOGENESIS; DMP1; TOOTH ROOT
ID TRANSCRIPTION FACTOR OSTERIX; HORMONE-RELATED PROTEIN; EPITHELIAL ROOT
SHEATH; BONE-FORMATION; OSTEOBLAST DIFFERENTIATION; TOOTH DEVELOPMENT;
IN-VITRO; DENTIN; EXPRESSION; MOUSE
AB To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of Osx and the formation of cellular cementum. We then generated 3.6-kilobase (kb) collagen type I (3.6-kb Col 1)-Osx transgenic mice, which displayed accelerated cementum formation versus wild-type (WT) controls. Importantly, the conditional deletion of Osx in the mesenchymal cells with two different Cre systems (the 2.3-kb Col 1 and an inducible CAGCre estrogen receptor [CreER]) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the Osx gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered scanning electron microscopy (SEM) and resin-casted SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support: (1) the mesenchymal origin of cellular cementum (from periodontal ligament [PDL] progenitor cells); (2) the vital role of OSX in controlling the formation of cellular cementum; and (3) the limited remodeling of cellular cementum in adult mice. (c) 2012 American Society for Bone and Mineral Research.
C1 [Cao, Zhengguo] Texas A&M Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX 75246 USA.
[Cao, Zhengguo] Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hu, Wuhan 430072, Peoples R China.
[Cao, Zhengguo] Wuhan Univ, Key Lab Oral Biomed, Minist Educ, Dept Periodontol,Sch & Hosp Stomatol, Wuhan 430072, Peoples R China.
[Zhou, Xin; de Crombrugghe, Benoit] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Xiao, Yin] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Somerman, Martha J.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Cao, ZG (reprint author), Texas A&M Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, 3302 Gaston Ave, Dallas, TX 75246 USA.
EM jfeng@bcd.tamhsc.edu
OI Xiao, Yin/0000-0003-1785-3491
FU NIH [DE018486]; National Natural Science Foundation of China [81170933]
FX This study was supported by grants from the NIH (DE018486 to JQF) and
the National Natural Science Foundation of China (81170933 to ZC).
NR 46
TC 37
Z9 39
U1 0
U2 18
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2012
VL 27
IS 5
BP 1080
EP 1092
DI 10.1002/jbmr.1552
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 927VW
UT WOS:000302939400012
PM 22246569
ER
PT J
AU Bhattacharyya, N
Wiench, M
Dumitrescu, C
Connolly, BM
Bugge, TH
Patel, HV
Gafni, RI
Cherman, N
Cho, M
Hager, GL
Collins, MT
AF Bhattacharyya, Nisan
Wiench, Malgorzata
Dumitrescu, Claudia
Connolly, Brian M.
Bugge, Thomas H.
Patel, Himatkumar V.
Gafni, Rachel I.
Cherman, Natasha
Cho, Monique
Hager, Gordon L.
Collins, Michael T.
TI Mechanism of FGF23 processing in fibrous dysplasia
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE FGF23; FIBROUS DYSPLASIA; McCUNE-ALBRIGHT SYNDROME; GNAS; Gsa;
ppGalNAcT3; FURIN; PHOSPHATE METABOLISM; RICKETS; OSTEOMALACIA;
PROCESSING
ID DOMINANT HYPOPHOSPHATEMIC RICKETS; FAMILIAL TUMORAL CALCINOSIS;
FIBROBLAST GROWTH FACTOR-23; PHOSPHATE HOMEOSTASIS; O-GLYCOSYLATION;
INDUCED OSTEOMALACIA; MINERAL METABOLISM; CLONING; FGF-23; BONE
AB Fibroblast growth factor-23 (FGF23) is a phosphate- and vitamin D-regulating hormone derived from osteoblasts/osteocytes that circulates in both active (intact, iFGF23) and inactive (C-terminal, cFGF23) forms. O-glycosylation by O-glycosyl transferase N-acetylgalactosaminyltransferase 3 (ppGalNAcT3) and differential cleavage by furin have been shown to be involved in regulating the ratio of active to inactive FGF23. Elevated iFGF23 levels are observed in a number of hypophosphatemic disorders, such as X-linked, autosomal recessive, and autosomal dominant hypophosphatemic rickets, whereas low iFGF23 levels are found in the hyperphosphatemic disorder familial tumoral calcinosis/hyperphosphatemic hyperostosis syndrome. Fibrous dysplasia of bone (FD) is associated with increased total FGF23 levels (cFGF23?+?iFGF23); however, classic hypophosphatemic rickets is uncommon. Our results suggest that it can be explained by increased FGF23 cleavage leading to an increase in inactive cFGF23 relative to active iFGF23. Given the fact that FD is caused by activating mutations in the small G-protein Gsa that results in increased cyclic adenosine monophosphate (cAMP) levels, we postulated that there may be altered FGF23 cleavage in FD and that the mechanism may involve alterations in cAMP levels and ppGalNacT3 and furin activities. Analysis of blood specimens from patients with FD confirmed that the elevated total FGF23 levels are the result of proportionally increased cFGF23 levels, consistent with less glycosylation and enhanced cleavage by furin. Analysis of primary cell lines of normal and mutation-harboring bone marrow stromal cells (BMSCs) from patients with FD demonstrated that BMSCs harboring the causative Gsa mutation had higher cAMP levels, lower ppGalNAcT3, and higher furin activity. These data support the model wherein glycosylation by ppGalNAcT3 inhibits FGF23 cleavage by furin and suggest that FGF23 processing is a regulated process that controls overall FGF23 activity in FD patients. (c) 2012 American Society for Bone and Mineral Research.
C1 [Bhattacharyya, Nisan; Dumitrescu, Claudia; Gafni, Rachel I.; Cherman, Natasha; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Wiench, Malgorzata; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Connolly, Brian M.; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Patel, Himatkumar V.] Natl Inst Diabet & Kidney Dis, Sect Biol Chem, NIH, Bethesda, MD USA.
[Cho, Monique] Natl Inst Diabet & Kidney Dis, Kidney Dis Branch, NIH, Bethesda, MD USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 218, Bethesda, MD 20892 USA.
EM mc247k@nih.gov
NR 34
TC 43
Z9 44
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2012
VL 27
IS 5
BP 1132
EP 1141
DI 10.1002/jbmr.1546
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 927VW
UT WOS:000302939400016
PM 22247037
ER
PT J
AU Barbour, KE
Houston, DK
Cummings, SR
Boudreau, R
Prasad, T
Sheu, Y
Bauer, DC
Tooze, JA
Kritchevsky, SB
Tylavsky, FA
Harris, TB
Cauley, JA
AF Barbour, Kamil E.
Houston, Denise K.
Cummings, Steven R.
Boudreau, Robert
Prasad, Tanushree
Sheu, Yahtyng
Bauer, Douglas C.
Tooze, Janet A.
Kritchevsky, Stephen B.
Tylavsky, Frances A.
Harris, Tamara B.
Cauley, Jane A.
CA Hlth ABC Study
TI Calciotropic hormones and the risk of hip and nonspine fractures in
older adults: The health ABC study
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE SERUM 25-HYDROXYVITAMIN D; PARATHYROID HORMONE; HIP FRACTURES; NONSPINE
FRACTURES
ID SERUM 25-HYDROXYVITAMIN D; VITAMIN-D DEFICIENCY; SECONDARY
HYPERPARATHYROIDISM; D SUPPLEMENTATION; BONE LOSS; WOMEN; ASSOCIATION;
MARKERS; MEN; DISABILITY
AB The effects of vitamin D and parathyroid hormone (PTH) levels on incident fracture remain uncertain. To test the hypothesis that increasing serum 25-hydroxyvitamin D [25(OH)D] and decreasing PTH levels are associated with decreased risk of hip and any nonspine fracture, we conducted a prospective cohort study among 2614 community-dwelling white and black participants, aged =70 years, from the Health, Aging and Body Composition (Health ABC) Study. Serum and plasma samples were drawn at year 2, which formed the baseline for this analysis. Serum 25(OH)D and intact PTH (1-84) were measured using radioimmunoassay with DiaSorin reagents and EDTA plasma with a two-site immunoradiometric assay kit, respectively. Incident fractures (hip and any nonspine) were assessed after year 2, every 6 months, by self-report and validated by radiology reports. The median (interquartile range) follow-up times for hip and any nonspine fractures were 6.4 (6.16.5) and 6.4 (5.56.5) years, respectively. Cox proportional hazards regression was used to estimate the hazard ratios (HR) with 95% confidence intervals (CI) for fracture. There were 84 hip and 247 nonspine fractures that occurred over the follow-up period. The multivariable adjusted HRs (95% CIs) of hip fracture for participants in the lowest (=17.78?ng/mL), second (17.79 to 24.36?ng/mL), and third quartiles (24.37 to 31.94?ng/mL) of 25(OH)D were 1.92 (0.97 to 3.83), 0.75 (0.32 to 1.72) and 1.86 (1.00 to 3.45), respectively, compared with participants in the highest 25(OH)D quartile (>31.94?ng/mL) (p trend?=?0.217). Additional adjustment for IL-6 (p?=?0.107), PTH (p?=?0.124), and hip areal bone mineral density (p?=?0.137) attenuated HRs of hip fracture in the lowest quartile by 16.3%, 17.4%, and 26.1%, respectively. There was no evidence of an association between 25(OH)D and any nonspine fractures, or between PTH and hip or any nonspine fractures. We found limited evidence to support an association between calciotropic hormones and hip and nonspine fractures in older men and women. (c) 2012 American Society for Bone and Mineral Research.
C1 [Barbour, Kamil E.; Boudreau, Robert; Prasad, Tanushree; Sheu, Yahtyng; Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA.
[Houston, Denise K.; Tooze, Janet A.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Sticht Ctr Aging, Dept Internal Med, Winston Salem, NC USA.
[Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Barbour, KE (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellefield Ave, Pittsburgh, PA 15213 USA.
EM barbourk@edc.pitt.edu
OI Boudreau, Robert/0000-0003-0162-5187; Kritchevsky,
Stephen/0000-0003-3336-6781; Cauley, Jane A/0000-0003-0752-4408
FU NIH, National Institute on Aging
FX The Health Aging and Body Composition Study (Health ABC) includes the
contract numbers N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106,
RO1-AG028050, RO1-NR012459, and WFUHS11200. This research was supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging.
NR 36
TC 6
Z9 7
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2012
VL 27
IS 5
BP 1177
EP 1185
DI 10.1002/jbmr.1545
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 927VW
UT WOS:000302939400021
PM 22228250
ER
PT J
AU Wentzensen, N
Gravitt, PE
Long, R
Schiffman, M
Dunn, ST
Carreon, JD
Allen, RA
Gunja, M
Zuna, RE
Sherman, ME
Gold, MA
Walker, JL
Wang, SS
AF Wentzensen, Nicolas
Gravitt, Patti E.
Long, Rodney
Schiffman, Mark
Dunn, S. Terence
Carreon, J. Daniel
Allen, Richard A.
Gunja, Munira
Zuna, Rosemary E.
Sherman, Mark E.
Gold, Michael A.
Walker, Joan L.
Wang, Sophia S.
TI Human Papillomavirus Load Measured by Linear Array Correlates with
Quantitative PCR in Cervical Cytology Specimens
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID REAL-TIME PCR; EARLY END-POINTS; VIRAL LOAD; NATURAL-HISTORY; CANCER;
DETERMINANTS; LESIONS; WOMEN; RISK; PROGRESSION
AB Carcinogenic human papillomavirus (HPV) infections are necessary causes of most anogenital cancers. Viral load has been proposed as a marker for progression to cancer precursors but has been confirmed only for HPV16. Challenges in studying viral load are related to the lack of validated assays for a large number of genotypes. We compared viral load measured by Linear Array (LA) HPV genotyping with the gold standard, quantitative PCR (Q-PCR). LA genotyping and Q-PCR were performed in 143 cytology specimens from women referred to colposcopy. LA signal strength was measured by densitometry. Correlation coefficients and receiver operating characteristic (ROC) analyses were used to evaluate analytical and clinical performance. We observed a moderate to strong correlation between the two quantitative viral load measurements, ranging from an R value of 0.61 for HPV31 to an R value of 0.86 for HPV52. We also observed agreement between visual LA signal strength evaluation and Q-PCR. Both quantifications agreed on the disease stages with highest viral load, which varied by type (cervical intraepithelial neoplasia grade 2 [CIN2] for HPV52, CIN3 for HPV16 and HPV33, and cancer for HPV18 and HPV31). The area under the curve (AUC) for HPV16 Q-PCR at the CIN3 cutoff was 0.72 (P = 0.004), and the AUC for HPV18 LA at the CIN2 cutoff was 0.78 (P = 0.04). Quantification of LA signals correlates with the current gold standard for viral load, Q-PCR. Analyses of viral load need to address multiple infections and type attribution to evaluate whether viral load has clinical value beyond the established HPV16 finding. Our findings support conducting comprehensive studies of viral load and cervical cancer precursors using quantitative LA genotyping data.
C1 [Wentzensen, Nicolas; Schiffman, Mark; Carreon, J. Daniel; Gunja, Munira; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 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.
[Long, Rodney] Natl Lib Med, Commun Engn Branch, Bethesda, MD USA.
[Dunn, S. Terence; Allen, Richard A.; Zuna, Rosemary E.; Walker, Joan L.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[Dunn, S. Terence; Allen, Richard A.; Zuna, Rosemary E.; Walker, Joan L.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA.
[Gold, Michael A.] Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Div Canc Etiol, Duarte, CA USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM wentzenn@mail.nih.gov
FU National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Cancer Institute.
NR 18
TC 15
Z9 15
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2012
VL 50
IS 5
BP 1564
EP 1570
DI 10.1128/JCM.06240-11
PG 7
WC Microbiology
SC Microbiology
GA 927II
UT WOS:000302900500011
PM 22337992
ER
PT J
AU Becker, A
Dark, T
Mason, T
Goodwin, B
AF Becker, A.
Dark, T.
Mason, T.
Goodwin, B.
TI 2005 Hurricane Surveillance: Measures to Reduce Carbon Monoxide
Poisoning in All Floridians
SO JOURNAL OF ENVIRONMENTAL HEALTH
LA English
DT Article
ID CARBOXYHEMOGLOBIN
AB The 2005 Florida hurricanes caused widespread power outages, increasing generator use that directly resulted in a surge in carbon monoxide (CO) poisonings. Of the 126 CO poisonings documented, 77% were related to generator use and 43% of these generators were placed outside but near a window. African-Americans and Latinos had a higher incidence of CO poisoning. The strength of the authors' study described here was the inclusion of the first responder network in one surveillance system for hurricane response. Notable advances have occurred since the authors' study, including CO poisoning listed as a reportable condition, regulation requiring CO detectors, CO generator warning labeling, and the development of a local surveillance and classification program for the county health departments. To prepare for future multiple hurricane seasons, comprehensive outreach should be focused at the local level through the first responder network and community groups to reduce CO poisonings in all populations.
C1 [Dark, T.] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Inst Publ Hlth, Tallahassee, FL 32307 USA.
[Mason, T.] Univ S Florida, Tampa, FL 33620 USA.
[Goodwin, B.] Natl Ctr Adv Translat Sci, Reno, NV USA.
RP Dark, T (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Inst Publ Hlth, Tallahassee, FL 32307 USA.
EM tyra.dark@famu.edu
FU Agency for Toxic Substances and Disease Registry [U61/ATU474148-3]
FX This work was funded by a grant received from the Agency for Toxic
Substances and Disease Registry (U61/ATU474148-3). Data were previously
reported in Becker et al., Florida Environmental Health Association
Journal, 195, 20-24.
NR 21
TC 0
Z9 0
U1 0
U2 2
PU NATL ENVIRON HEALTH ASSOC
PI DENVER
PA 720 S COLORADO BLVD SUITE 970, SOUTH TOWER, DENVER, CO 80246 USA
SN 0022-0892
J9 J ENVIRON HEALTH
JI J. Environ. Health
PD MAY
PY 2012
VL 74
IS 9
BP 16
EP 21
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 929UF
UT WOS:000303090500003
PM 22590847
ER
PT J
AU Soto, E
Romero, R
Kusanovic, JP
Ogge, G
Hussein, Y
Yeo, L
Hassan, SS
Kim, CJ
Chaiworapongsa, T
AF Soto, Eleazar
Romero, Roberto
Kusanovic, Juan Pedro
Ogge, Giovanna
Hussein, Youssef
Yeo, Lami
Hassan, Sonia S.
Kim, Chong Jai
Chaiworapongsa, Tinnakorn
TI Late-onset preeclampsia is associated with an imbalance of angiogenic
and anti-angiogenic factors in patients with and without placental
lesions consistent with maternal underperfusion
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Placental growth factor (PlGF); soluble endoglin (sEng); soluble
vascular endothelial growth factor receptor-1 (sVEGFR-1); soluble
vascular endothelial growth factor receptor-2 (sVEGFR-2); ischemic
placenta
ID ENDOTHELIAL GROWTH-FACTOR; UTERINE ARTERY DOPPLER; PREGNANCY-INDUCED
HYPERTENSION; FOR-GESTATIONAL-AGE; FACTOR RECEPTOR-1 CONCENTRATION;
TYROSINE KINASE-1 EXPRESSION; HEALTHY NULLIPAROUS WOMEN;
INNATE-IMMUNE-SYSTEM; SOLUBLE ENDOGLIN; UNITED-STATES
AB Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late-and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p < 0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p < 0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.
C1 [Soto, Eleazar; Romero, Roberto; Kusanovic, Juan Pedro; Ogge, Giovanna; Hussein, Youssef; Yeo, Lami; Hassan, Sonia S.; Kim, Chong Jai; Chaiworapongsa, Tinnakorn] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Soto, Eleazar; Kusanovic, Juan Pedro; Ogge, Giovanna; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA.
RP Chaiworapongsa, T (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; tchaiwor@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 154
TC 43
Z9 45
U1 0
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD MAY
PY 2012
VL 25
IS 5
BP 498
EP 507
DI 10.3109/14767058.2011.591461
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 926ZI
UT WOS:000302873200010
PM 21867402
ER
PT J
AU Palumbo, S
Toscano, CD
Parente, L
Weigert, R
Bosetti, F
AF Palumbo, Sara
Toscano, Christopher D.
Parente, Laura
Weigert, Roberto
Bosetti, Francesca
TI The cyclooxygenase-2 pathway via the PGE2 EP2 receptor contributes to
oligodendrocytes apoptosis in cuprizone-induced demyelination
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE arachidonic acid; cuprizone; cyclooxygenases; demyelination; EP2; myelin
ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; PROSTANOID RECEPTORS;
GENE-EXPRESSION; BRAIN; INHIBITORS; DISEASE; CELLS; COX-2; MODEL
AB Cyclooxygenases (COX)-1 and -2 are key enzymes required for the conversion of arachidonic acid to eicosanoids, potent mediators of inflammation. In patients with multiple sclerosis, COX-2 derived prostaglandins (PGs) are elevated in the CSF and COX-2 is up-regulated in demyelinating plaques. However, it is not known whether COX-2 activity contributes to oligodendrocyte death. In cuprizone-induced demyelination, oligodendrocyte apoptosis and a concomitant increase in the gene expression of COX-2 and PGE2-EP2 receptor precede histological demyelination. COX-2 and EP2 receptor were expressed by oligodendrocytes, suggesting a causative role for the COX-2/EP2 pathway in the initiation of oligodendrocyte death and demyelination. COX-2 gene deletion, chronic treatment with the COX-2 selective inhibitor celecoxib, or with the EP2 receptor antagonist AH6809 reduced cuprizone-induced oligodendrocyte apoptosis, the degree of demyelination and motor dysfunction. These data indicate that the PGE2 EP2 receptor contributes to oligodendrocyte apoptosis and open possible new therapeutic approaches for multiple sclerosis.
C1 [Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Parente, Laura; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Room 1S126 MSC 0947, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
RI palumbo, sara/B-1603-2013
OI palumbo, sara/0000-0002-3809-6058
FU NIH, National Institute on Aging; National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging and National Institute of Dental and
Craniofacial Research.
NR 43
TC 11
Z9 11
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2012
VL 121
IS 3
BP 418
EP 427
DI 10.1111/j.1471-4159.2011.07363.x
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 923JN
UT WOS:000302615700010
PM 21699540
ER
PT J
AU Boghossian, NS
Horbar, JD
Carpenter, JH
Murray, JC
Bell, EF
AF Boghossian, Nansi S.
Horbar, Jeffrey D.
Carpenter, Joseph H.
Murray, Jeffrey C.
Bell, Edward F.
CA Vermont Oxford Network
TI Major Chromosomal Anomalies among Very Low Birth Weight Infants in the
Vermont Oxford Network
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID NATURAL-HISTORY; PRETERM INFANTS; TRISOMY-18; SURVIVAL; MANAGEMENT;
MALFORMATIONS; PREVALENCE; RATES
AB Objective To examine prevalence, characteristics, interventions, and mortality of very low birth weight (VLBW) infants with trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), or triploidy.
Study design Infants with birth weight 401-1500 g admitted to centers of the Vermont Oxford Network during 1994-2009 were studied. A majority of the analyses are presented as descriptive data. Median survival times and their 95% CIs were estimated using the Kaplan-Meier approach.
Results Of 539 509 VLBW infants, 1681 (0.31%) were diagnosed with T21, 1416 (0.26%) with T18, 435 (0.08%) with T13, and 116 (0.02%) with triploidy. Infants with T18 were the most likely to be growth restricted (79.7%). Major surgery was reported for 30.4% of infants with T21, 9.2% with T18, 6.4% with T13, and 4.8% with triploidy. Hospital mortality occurred among 33.1% of infants with T21, 89.0% with T18, 92.4% with T13, and 90.5% with triploidy. Median survival time was 4 days (95% CI, 3-4) among infants with T18 and 3 days (95% CI, 2-4) among both infants with T13 and infants with triploidy.
Conclusion In this cohort of VLBW infants, survival among infants with T18, T13, or triploidy was very poor. This information can be used to counsel families. (J Pediatr 2012;160:774-80).
C1 [Boghossian, Nansi S.; Murray, Jeffrey C.; Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Horbar, Jeffrey D.; Carpenter, Joseph H.] Vermont Oxford Network, Burlington, VT USA.
[Horbar, Jeffrey D.] Univ Vermont, Dept Pediat, Burlington, VT USA.
RP Boghossian, NS (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res Eunice Kennedy S, 6100 Execut Blvd,Room 7B03C, Bethesda, MD 20892 USA.
EM nansi.boghossinan@nih.gov
FU NICHD NIH HHS [R01 HD057192, R01 HD052953]
NR 28
TC 7
Z9 8
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAY
PY 2012
VL 160
IS 5
BP 774
EP U318
DI 10.1016/j.jpeds.2011.11.005
PG 18
WC Pediatrics
SC Pediatrics
GA 928OQ
UT WOS:000302992800018
PM 22177989
ER
PT J
AU Carlo, WA
Goudar, SS
Pasha, O
Chomba, E
McClure, EM
Biasini, FJ
Wallander, JL
Thorsten, V
Chakraborty, H
Wright, LL
AF Carlo, Waldemar A.
Goudar, Shivaprasad S.
Pasha, Omrana
Chomba, Elwyn
McClure, Elizabeth M.
Biasini, Fred J.
Wallander, Jan L.
Thorsten, Vanessa
Chakraborty, Hrishikesh
Wright, Linda L.
TI Neurodevelopmental Outcomes in Infants Requiring Resuscitation in
Developing Countries
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PERINATAL-MORTALITY; NEONATAL ENCEPHALOPATHY; BIRTH ASPHYXIA; APGAR
SCORE; AGE; POPULATION; ADAPTATION; SUBSEQUENT; DISABILITY; KATHMANDU
AB Objective To determine whether resuscitation of infants who failed to develop effective breathing at birth increases survivors with neurodevelopmental impairment.
Study design Infants unresponsive to stimulation who received bag and mask ventilation at birth in a resuscitation trial and infants who did not require any resuscitation were randomized to early neurodevelopmental intervention or control groups. Infants were examined by trained neurodevelopmental evaluators masked to both their resuscitation history and intervention group. The 12-month neurodevelopmental outcome data for both resuscitated and non-resuscitated infants randomized to the control groups are reported.
Results The study provided no evidence of a difference between the resuscitated infants (n = 86) and the non-resuscitated infants (n = 115) in the percentage of infants at 12 months with a Mental Developmental Index <85 on the Bayley Scales of Infant Development-II (primary outcome; 18% versus 12%; P=.22) and in other neurodevelopmental outcomes.
Conclusions Most infants who received resuscitation with bag and mask ventilation at birth have 12-month neurodevelopmental outcomes in the reference range. Longer follow-up is needed because of increased risk for neurodevelopmental impairments. (J Pediatr 2012;160:781-85).
C1 [Carlo, Waldemar A.; Biasini, Fred J.] Univ Alabama Birmingham, Birmingham, AL 35233 USA.
[Carlo, Waldemar A.; Chomba, Elwyn] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Goudar, Shivaprasad S.] Jawaharlal Nehru Med Coll, Belgaum, India.
[Pasha, Omrana] Aga Kahn Univ Med Coll, Karachi, Pakistan.
[Chomba, Elwyn] Univ Zambia, Lusaka, Zambia.
[McClure, Elizabeth M.; Thorsten, Vanessa; Chakraborty, Hrishikesh] Res Triangle Inst Int, Durham, NC USA.
[Wallander, Jan L.] Univ Calif, Merced, CA USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Carlo, WA (reprint author), Univ Alabama Birmingham, 1700 6th Ave S 176F,Suite 9380R, Birmingham, AL 35233 USA.
EM wcarlo@peds.uab.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Global Network for Women's and Children's Health Research;
National Institute of Neurological Disorders and Stroke [HD43464,
HD42372, HD40607, HD40636]; Fogarty International Center [TW006703];
Division of Neonatology, Department of Pediatrics, University of Alabama
at Birmingham
FX Funded by the Eunice Kennedy Shriver National Institute of Child Health
and Human Development Global Network for Women's and Children's Health
Research and the National Institute of Neurological Disorders and Stroke
(grants HD43464, HD42372, HD40607, and HD40636) and the Fogarty
International Center (grant TW006703), and the Division of Neonatology,
Department of Pediatrics, University of Alabama at Birmingham. The
authors declare no conflicts of interest.
NR 24
TC 7
Z9 7
U1 2
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAY
PY 2012
VL 160
IS 5
BP 781
EP U324
DI 10.1016/j.jpeds.2011.10.007
PG 6
WC Pediatrics
SC Pediatrics
GA 928OQ
UT WOS:000302992800019
PM 22099522
ER
PT J
AU Koek, W
France, CP
Cheng, KJ
Rice, KC
AF Koek, Wouter
France, Charles P.
Cheng, Kejun
Rice, Kenner C.
TI Effects of the GABA(B) Receptor-Positive Modulators CGP7930 and rac-BHFF
in Baclofen- and gamma-Hydroxybutyrate-Discriminating Pigeons
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ALCOHOL-PREFERRING RATS; ALLOSTERIC MODULATOR; DIFFERENTIAL ANTAGONISM;
MOTIVATIONAL PROPERTIES; BINDING CHARACTERISTICS; TIME-COURSE; IN-VIVO;
GS39783; ACID; GHB
AB In vivo effects of GABA(B) receptor-positive modulators suggest them to have therapeutic potential to treat central nervous system disorders such as anxiety and drug abuse. Although these effects are thought to be mediated by positive modulation of GABA(B) receptors, such modulation has been examined primarily in vitro. This study further examined the in vivo properties of the GABA(B) receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF). In pigeons discriminating baclofen from saline, gamma-hydroxybutyrate (GHB) produced 100% baclofen-appropriate responding, and the GABA(B) antagonist 3-aminopropyl(dimethoxymethyl) phosphinic acid (CGP35348) blocked the effects of both drugs. CGP7930 and rac-BHFF produced at most 41 and 74% baclofen-appropriate responding, respectively, and enhanced the discriminative stimulus effects of baclofen, but not of GHB. In pigeons discriminating GHB from saline, CGP7930 and rac-BHFF produced at most 1 and 49% GHB-appropriate responding, respectively, and enhanced the effects of baclofen, but not of GHB. Enhancement of the discriminative stimulus effects of baclofen by rac-BHFF and CGP7930 is further evidence of their effectiveness as GABA(B) receptor-positive modulators in vivo. Furthermore, lack of complete substitution of the positive modulators rac-BHFF and CGP7930 for baclofen and GHB suggests that their discriminative stimulus effects differ from those of GABA(B) receptor agonists. Finally, together with converging evidence that the GABA(B) receptor populations mediating the effects of baclofen and GHB are not identical, the present findings suggest that these populations differ in their susceptibility to positive modulatory effects. Such differences could allow for more selective therapeutic targeting of the GABA(B) system.
C1 [Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Cheng, Kejun; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
RP Koek, W (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr,Mail Code 7792, San Antonio, TX 78229 USA.
EM koek@uthscsa.edu
FU National Institutes of Health National Institute on Drug Abuse [DA15692,
DA17918]; National Institute on Drug Abuse; National Institutes of
Health National Institute on Alcohol Abuse and Alcoholism
FX This work was supported by the National Institutes of Health National
Institute on Drug Abuse [Grants DA15692, DA17918]; the Intramural
Research Programs of the National Institute on Drug Abuse; and the
National Institutes of Health National Institute on Alcohol Abuse and
Alcoholism.
NR 47
TC 12
Z9 12
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAY
PY 2012
VL 341
IS 2
BP 369
EP 376
DI 10.1124/jpet.111.190975
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 927JM
UT WOS:000302903500007
PM 22319197
ER
PT J
AU Miller, AC
Rashid, RM
Falzon, L
Elamin, EM
Zehtabchi, S
AF Miller, Andrew C.
Rashid, Rashid M.
Falzon, Louise
Elamin, Elamin M.
Zehtabchi, Shahriar
TI Silver sulfadiazine for the treatment of partial-thickness burns and
venous stasis ulcers
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE burns; silver sulfadiazine; stasis dermatitis ulcer; wounds and injuries
ID TRIAL; WOUNDS; RATS
AB Background: For decades silver-containing antibiotics such as silver sulfadiazine (SSD) have been applied as standard topical therapy for patients with partial-thickness burns and venous stasis ulcers. This evidence-based review intends to answer the following research question: in ambulatory patients with partial-thickness burns or stasis dermatitis ulcers, does the use of topical SSD compared with nonantibiotic dressings improve mortality, wound healing, re-epithelialization, or infection rates?
Methods: MEDLINE, EMBASE, Cochrane Library, and other databases were searched. We considered trials that enrolled patients of any age with partial-thickness burns or venous stasis ulcers and randomized them to either topical SSD or placebo, saline-soaked gauze, paraffin gauze, sterile dry dressing, or nonantibiotic moist dressing. Outcomes included mortality, wound healing, speed of re-epithelialization, and infection rates.
Results: For burns, our search revealed 400 potential articles. No human studies met the inclusion criteria. Only 7 animal studies (1 mouse, 4 rat, and 2 pig) were relevant to the proposed question. These animal studies provided conflicting results. Whereas some support the use of SSD for treatment of partial-thickness burns, others question its effectiveness. For stasis dermatitis ulcer, the search identified 50 articles for review, of which 20 abstracts were reviewed, and one article met the inclusion criteria. This study did not show any significant improvement in the rate of complete healing in SSD group compared with placebo either at 4 weeks (relative risk 6.2, 95% confidence interval 0.8-48) or at 1 year (relative risk 5.2, 95% confidence interval 0.6-41.6) of follow-up.
Conclusion: There is insufficient evidence to either support or refute the routine use of SSD for ambulatory patients with either partial-thickness burns or stasis dermatitis ulcers to decrease mortality, prevent infection, or augment wound healing in human beings. (J Am Acad Dermatol 2012;66:e159-65.)
C1 [Miller, Andrew C.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Miller, Andrew C.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA.
[Rashid, Rashid M.] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX USA.
[Falzon, Louise] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, New York, NY USA.
[Elamin, Elamin M.] James A Haley Vet Hosp, Dept Pulm Crit Care & Sleep Med, Tampa, FL 33612 USA.
[Zehtabchi, Shahriar] Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY USA.
[Zehtabchi, Shahriar] Kings Cty Hosp Ctr, Brooklyn, NY USA.
RP Rashid, RM (reprint author), 6655 Travis,Suite 980, Houston, TX 77030 USA.
EM rashidrashid.mdphd@yahoo.com
OI Falzon, Louise/0000-0002-9449-6056; Miller, Andrew/0000-0001-8474-5090
NR 18
TC 11
Z9 11
U1 0
U2 11
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD MAY
PY 2012
VL 66
IS 5
BP E159
EP E165
DI 10.1016/j.jaad.2010.06.014
PG 7
WC Dermatology
SC Dermatology
GA 926UZ
UT WOS:000302858700004
PM 20724028
ER
PT J
AU Lau, YF
Wright, AR
Subbarao, K
AF Lau, Yuk-Fai
Wright, Amber R.
Subbarao, Kanta
TI The Contribution of Systemic and Pulmonary Immune Effectors to
Vaccine-Induced Protection from H5N1 Influenza Virus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD8(+) T-CELLS; A VIRUS; IMMUNOGLOBULIN-A; HETEROSUBTYPIC IMMUNITY;
ANTIBODY-RESPONSES; LOCAL IMMUNITY; H1N1 VACCINE; CROSS-REACT; B-CELLS;
LIVE
AB Live attenuated influenza vaccines (LAIVs) are effective in providing protection against influenza challenge in animal models and in preventing disease in humans. We previously showed that LAIVs elicit a range of immune effectors and that successful induction of pulmonary cellular and humoral immunity in mice requires pulmonary replication of the vaccine virus. An upper respiratory tract immunization (URTI) model was developed in mice to mimic the human situation, in which the vaccine virus does not replicate in the lower respiratory tract, allowing us to assess the protective efficacy of an H5N1 LAIV against highly pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity. Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza-specific lymphocytes are the main contributors to clearance of challenge virus from the lungs and that contributions of influenza-specific enzyme-linked immunosorbent assay (ELISA) antibodies in serum and splenic CD8(+) T cells were negligible. Complete protection from H5N1 challenge was achieved after two doses of H5N1 LAIV and was associated with maturation of the antibody response. Although passive transfer of sera from mice that received two doses of vaccine prevented lethality in naive recipients following challenge, the mice showed significant weight loss, with high pulmonary titers of the H5N1 virus. These data highlight the importance of mucosal immunity in mediating optimal protection against H5N1 infection. Understanding the requirements for effective induction and establishment of these protective immune effectors in the respiratory tract paves the way for a more rational and effective vaccine approach in the future.
C1 [Lau, Yuk-Fai; Wright, Amber R.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH Bethesda, Bethesda, MD USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH Bethesda, Bethesda, MD USA.
EM ksubbarao@niaid.nih.gov
FU National Institutes of Health (NIH); National Institute of Allergy and
Infectious Diseases (NIAID)
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH) and the National Institute of
Allergy and Infectious Diseases (NIAID).
NR 51
TC 11
Z9 11
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 9
BP 5089
EP 5098
DI 10.1128/JVI.07205-11
PG 10
WC Virology
SC Virology
GA 925RD
UT WOS:000302777800032
PM 22379093
ER
PT J
AU Pagan, I
Holmes, EC
Simon-Loriere, E
AF Pagan, Israel
Holmes, Edward C.
Simon-Loriere, Etienne
TI Level of Gene Expression Is a Major Determinant of Protein Evolution in
the Viral Order Mononegavirales
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID STRAND RNA VIRUSES; CODON USAGE BIAS; MOLECULAR EVOLUTION; SUBSTITUTION
RATES; HIGH-THROUGHPUT; P PROTEIN; YEAST; DISPENSABILITY;
IDENTIFICATION; CENTRALITY
AB Although the rate at which proteins change is a key parameter in molecular evolution, its determinants are poorly understood in viruses. A variety of factors, including gene length, codon usage bias, protein abundance, protein function, and gene expression level, have been shown to affect the rate of protein evolution in a diverse array of organisms. However, the role of these factors in viral evolution has yet to be addressed. The polar 3'-5' stepwise attenuation of transcription in the Mononegavirales, a group of single-strand negative-sense RNA viruses, provides a unique system to explore the determinants of protein evolution in viruses. We analyzed the relative importance of a variety of factors in shaping patterns of sequence variation in full-length genomes from 13 Mononegavirales species. Our analysis suggests that the level of gene expression, and by extension the relative genomic position of each gene, is a key determinant of the protein evolution in these viruses. This appears to be the consequence of selection for translational robustness, but not for translational accuracy, in highly expressed genes. The small genome size and number of proteins encoded by these viruses allowed us to identify other protein-specific factors that may also play a role in virus evolution, such as host-virus interactions and functional constraints. Finally, we explored the evolutionary pressures acting on noncoding regions in Mononegavirales genomes and observed that, despite being less constrained than coding regions, their evolutionary rates are also associated with genomic position.
C1 [Pagan, Israel; Holmes, Edward C.; Simon-Loriere, Etienne] 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 Pagan, I (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM jesusisrael.pagan@upm.es
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Holmes, Edward/0000-0001-9596-3552; ,
Etienne/0000-0001-8420-7743
FU Marie Curie Fellowship [PIOF-GA-2009-236470]; National Institutes of
Health [R01 GM080533-5]
FX This study was supported by a Marie Curie Fellowship PIOF-GA-2009-236470
to I.P. and National Institutes of Health grant R01 GM080533-5 to E.C.H.
NR 72
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 9
BP 5253
EP 5263
DI 10.1128/JVI.06050-11
PG 11
WC Virology
SC Virology
GA 925RD
UT WOS:000302777800045
PM 22345453
ER
PT J
AU Blazkova, J
Murray, D
Justement, JS
Funk, EK
Nelson, AK
Moir, S
Chun, TW
Fauci, AS
AF Blazkova, Jana
Murray, Danielle
Justement, J. Shawn
Funk, Emily K.
Nelson, Amy K.
Moir, Susan
Chun, Tae-Wook
Fauci, Anthony S.
TI Paucity of HIV DNA Methylation in Latently Infected, Resting CD4(+) T
Cells from Infected Individuals Receiving Antiretroviral Therapy
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CPG METHYLATION; TRANSCRIPTIONAL ACTIVITY; PLASMA VIREMIA; SUPPRESSION;
RESERVOIR; VECTORS
AB Maintenance of HIV latency in vitro has been linked to methylation of HIV DNA. However, examinations of the degree of methylation of HIV DNA in the latently infected, resting CD4(+) T cells of infected individuals receiving antiretroviral therapy have been limited. Here, we show that methylation of the HIV 5' long terminal repeat (LTR) in the latent viral reservoir of HIV-infected aviremic individuals receiving therapy is rare, suggesting that other mechanisms are likely involved in the persistence of viral latency.
C1 [Blazkova, Jana; Murray, Danielle; Justement, J. Shawn; Funk, Emily K.; Nelson, Amy K.; Moir, Susan; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chun, TW (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twchun@nih.gov
NR 13
TC 31
Z9 31
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 9
BP 5390
EP 5392
DI 10.1128/JVI.00040-12
PG 3
WC Virology
SC Virology
GA 925RD
UT WOS:000302777800060
PM 22345448
ER
PT J
AU San-Juan-Vergara, H
Sampayo-Escobar, V
Reyes, N
Cha, B
Pacheco-Lugo, L
Wong, T
Peeples, ME
Collins, PL
Castano, ME
Mohapatra, SS
AF San-Juan-Vergara, Homero
Sampayo-Escobar, Viviana
Reyes, Niradiz
Cha, Byeong
Pacheco-Lugo, Lisandro
Wong, Terianne
Peeples, Mark E.
Collins, Peter L.
Castano, Maria Eugenia
Mohapatra, Shyam S.
TI Cholesterol-Rich Microdomains as Docking Platforms for Respiratory
Syncytial Virus in Normal Human Bronchial Epithelial Cells (vol 86, pg
1832, 2012)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [San-Juan-Vergara, Homero] Fdn Univ Norte, Dept Med, Barranquilla, Colombia.
Univ S Florida, Dept Internal Med, Div Translat Med, Nanomed Res Ctr, Tampa, FL 33612 USA.
Univ Cartagena, Fac Med, Cartagena De Indias, Colombia.
Univ S Florida, Coll Med, Lisa Muma Weitz Lab Adv Microscopy & Cell Imaging, Tampa, FL USA.
Univ Simon Bolivar, Fac Med, Barranquilla, Colombia.
Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.
Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
James A Haley VA Hosp, Tampa, FL USA.
NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP San-Juan-Vergara, H (reprint author), Fdn Univ Norte, Dept Med, Barranquilla, Colombia.
RI Mohapatra, Shyam/C-2500-2012
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 9
BP 5408
EP 5408
DI 10.1128/JVI.00558-12
PG 1
WC Virology
SC Virology
GA 925RD
UT WOS:000302777800068
ER
PT J
AU Ferris, RL
Stefanika, P
Xi, LQ
Gooding, W
Seethala, RR
Godfrey, TE
AF Ferris, Robert L.
Stefanika, Patrick
Xi, Liqiang
Gooding, William
Seethala, Raja R.
Godfrey, Tony E.
TI Rapid molecular detection of metastatic head and neck squamous cell
carcinoma as an intraoperative adjunct to sentinel lymph node biopsy
SO LARYNGOSCOPE
LA English
DT Article
DE Sentinel node biopsy; molecular staging; oral cancer; metastasis;
real-time polymerase chain reaction; Level of Evidence: 4
ID ORAL-CAVITY; CANCER PATIENTS; ELEVATED LEVELS; MESSENGER-RNA;
DISSECTION; MICROMETASTASES; EXPRESSION; OROPHARYNX; MANAGEMENT
AB Objectives/Hypothesis: Clinical staging of early head and neck squamous cell carcinoma (SCCHN) is often inaccurate, leading to elective neck dissection to detect the 30% of patients with micrometastatic disease. Sentinel node biopsy accurately stages the regional lymphatics, but intraoperative pathology is only moderately sensitive, and final pathology takes several days to complete. To facilitate immediate neck dissection where necessary, we have identified several promising marker genes of SCCHN metastasis and developed a rapid, accurate, and automated quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) assay for intraoperative use.
Study Design: Prospective tissue collection, retrospective pathologic correlation with qRT-PCR.
Methods: From a 40-gene marker screen, we quantified expression of 11 potential tumor genes using a test set of primary tumors (n = 32) and metastatic (n 19) and benign (n 10) lymph nodes. Eight patients' paired primary tumor and metastatic nodes were included. A validation set of 442 grossly tumor-negative nodes was evaluated for expression of the most promising markers, comparing metastasis detection by qRT-PCR with pathologic analysis (hematoxylin and eosin and immunohistochemistry). A novel multiplexed, automated, single-tube qRT-PCR assay was used to analyze more than 100 lymph nodes using a two-marker, 35-minute assay to determine its negative predictive value.
Results: Based on expression of 11 tumor-associated genes from the marker screen, the two most promising markers of SCCHN metastasis in the test set, pemphigus vulgaris antigen (PVA) and tumor-associated calcium signal transducer 1 (TACSTD1), also known as epithelial cell adhesion molecule (EpCAM), were selected. Development of a multiplexed qRT-PCR assay for the detection of metastasis compared favorably with pathologic analysis in the additional 442-node set. A rapid, multiplexed assay using PVA and TACSTD1 demonstrated excellent reproducibility, linearity, and accuracy (approximate to 96% negative predictive value) for identifying positive (n 40) and negative (n 62) nodes in a validation subset.
Conclusions: Detection of metastatic SCCHN using multiplexed qRT-PCR can be rapid, accurate, and automated and may enable sentinel node biopsy to be used for intraoperative decision-making. PCR amplification of tumor marker genes is an effective method of intraoperative molecular staging of SCCHN and could more appropriately guide application of neck dissection in pN+ SCCHN patients, sparing 60% to 70% of pN0 patients from unnecessary neck dissection. This technique may also be used for identifying residual neck disease posttreatment, using outpatient fine-needle aspiration biopsy specimens.
C1 [Ferris, Robert L.] Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Pittsburgh, PA 15213 USA.
[Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA.
[Ferris, Robert L.] Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA 15213 USA.
[Seethala, Raja R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
[Xi, Liqiang] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Gooding, William] Univ Pittsburgh, Biostat Facil, Inst Canc, Pittsburgh, PA 15213 USA.
[Godfrey, Tony E.] Univ Rochester, Dept Surg, Rochester, NY USA.
[Stefanika, Patrick] Bratislava Univ, Dept Otolaryngol, Bratislava, Slovakia.
RP Ferris, RL (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Suite 500,203 Lothrop St, Pittsburgh, PA 15213 USA.
EM ferrl@upmc.edu
RI Godfrey, Tony/A-5572-2013;
OI Godfrey, Tony/0000-0002-3283-6983; Ferris, Robert/0000-0001-6605-2071
FU NCI, University of Pittsburgh Oral Cancer Center [R01 CA90665]
FX Funding was provided by NCI R01 CA90665 (R.L.F., T.E.G.), University of
Pittsburgh Oral Cancer Center pilot grant. The authors have no other
funding, financial relationships, or conflicts of interest to disclose.
NR 32
TC 15
Z9 16
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD MAY
PY 2012
VL 122
IS 5
BP 1020
EP 1030
DI 10.1002/lary.22467
PG 11
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 927XY
UT WOS:000302945100016
PM 22447185
ER
PT J
AU Neta, G
Yu, CL
Brenner, A
Gu, FY
Hutchinson, A
Pfeiffer, R
Sturgis, EM
Xu, L
Linet, MS
Alexander, BH
Chanock, S
Sigurdson, AJ
AF Neta, Gila
Yu, Chu-Ling
Brenner, Alina
Gu, Fangyi
Hutchinson, Amy
Pfeiffer, Ruth
Sturgis, Erich M.
Xu, Li
Linet, Martha S.
Alexander, Bruce H.
Chanock, Stephen
Sigurdson, Alice J.
TI Common genetic variants in the 8q24 region and risk of papillary thyroid
cancer
SO LARYNGOSCOPE
LA English
DT Article
DE 8q24; thyroid cancer; single nucleotide polymorphisms; Level of
Evidence: 3b
ID GENOME-WIDE ASSOCIATION; US RADIOLOGIC TECHNOLOGISTS; PROSTATE-CANCER;
SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; MULTIPLE LOCI; CARCINOMA
AB Objectives/Hypothesis: Single nucleotide polymorphisms (SNPs) in the 8q24 chromosomal region identified from genome-wide scans have been associated with the risk of several cancers, including breast (rs1562430), prostate (rs1447295), and colon (rs6983267). A genome-wide scan in 26 families with papillary thyroid cancer (PTC) also found susceptibility loci in 8q24, supporting a closer evaluation of this chromosomal region in relation to the risk of sporadic PTC.
Study Design: Case-control study.
Methods: We evaluated 157 tag SNPs in the 8q24 chromosomal region between 120.91 Mb and 128.78 Mb (including rs1562430, rs1447295, and rs6983267) in a case-control study of 344 PTC cases and 452 age and gender frequency-matched controls. We used logistic regression to estimate odds ratios and compute P values of linear trend for PTC with genotypes of interest. To account for multiple comparisons, we applied the false discovery rate (FDR) method.
Results: We did not find a significant association between rs1562430, rs1447295, or rs6983267 and PTC risk. We found that one SNP (rs4733616) was associated with PTC risk at P = .003, and 12 other SNPs were associated with PTC risk at P < .05. However, no SNPs remained significant after FDR correction.
Conclusions: Our findings do not support a strong association between SNPs in the 8q24 chromosomal region and risk of sporadic PTC, but several SNPs with small effects might exist.
C1 [Neta, Gila; Yu, Chu-Ling; Brenner, Alina; Linet, Martha S.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Gu, Fangyi] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Pfeiffer, Ruth] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Hutchinson, Amy] SAIC Frederick Inc, Core Genotyping Facil, NCI Frederick, Frederick, MD USA.
[Sturgis, Erich M.; Xu, Li] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA.
[Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Gaithersburg, MD USA.
RP Neta, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7049,6120 Execut Blvd, Bethesda, MD 20852 USA.
EM netagil@mail.nih.gov
RI Xu, Li/B-9535-2012; Gu, Fangyi/I-5957-2014
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; American Thyroid Association; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
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, and by a grant from the
American Thyroid Association (PI: E. M. Sturgis). 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
organizations imply endorsement by the US government. The authors have
no other funding, financial relationships, or conflicts of interest to
disclose.
NR 19
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD MAY
PY 2012
VL 122
IS 5
BP 1040
EP 1042
DI 10.1002/lary.23209
PG 3
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 927XY
UT WOS:000302945100019
PM 22275265
ER
PT J
AU Feng, X
Zhang, T
Ralston, E
Ludlow, CL
AF Feng, Xin
Zhang, Tan
Ralston, Evelyn
Ludlow, Christy L.
TI Differences in neuromuscular junctions of laryngeal and limb muscles in
rats
SO LARYNGOSCOPE
LA English
DT Article
DE Laryngeal muscle; neuromuscular junction; single fiber; cluster
fragments; gender difference; rat
ID ABDUCTOR SPASMODIC DYSPHONIA; MDX MOUSE; THYROARYTENOID MUSCLE;
MULTI-INNERVATION; BOTULINUM TOXIN; FIBERS; EXPRESSION; DIAPHRAGM;
FATIGUE; SYNAPSE
AB Objectives/Hypothesis: Laryngeal muscles are specialized for fine control of voice, speech, and swallowing, and may differ from limb muscles in many aspects. Because muscles and their controlling motor neurons communicate via neuromuscular junctions (NMJs), we hypothesized that NMJs in laryngeal muscles have specialized characteristics different from limb muscles.
Study Design: In vivo study.
Methods: Single muscle fibers from 12 Sprague-Dawley rats (six male, six female) were used to analyze the postsynaptic side of NMJs from laryngeal thyroarytenoid (TA), cricothyroid (CT), posterior cricoarytenoid (PCA), limb soleus (SOL), and extensor digitorum longus (EDL) muscles. NMJs were labeled with rhodamine-conjugated a-bungarotoxin. With confocal microscopy, we counted cluster fragments and measured the NMJ area, both absolute and normalized (corrected by muscle fiber diameter), for at least 10 single fibers from each muscle of each animal. Differences between genders were also compared.
Results: Cluster fragments of postsynaptic NMJs were more numerous in PCA and TA compared to CT, SOL, and EDL muscles (P <.01) in both male and female rats. NMJ cluster fragments were more numerous in female than in male rats only in the TA muscle (P <.01). The absolute area covered by the NMJs showed SOL > EDL > PCA > CT > TA (P <.01); however, with normalization the SOL EDL PCA > CT TA.
Conclusions: Differences found in NMJ surface and organization between laryngeal and limb muscle fibers may relate to specialized laryngeal muscle functions. Differences in NMJs between male and female rats were found only in the TA muscle, suggesting an underlying mechanism for some gender-specific laryngeal disorders related to abnormal TA muscle activity.
C1 [Feng, Xin] Wake Forest Univ, Bowman Gray Sch Med, Dept Otolaryngol, Winston Salem, NC 27157 USA.
[Feng, Xin; Ludlow, Christy L.] NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Tan; Ralston, Evelyn] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD USA.
[Ludlow, Christy L.] James Madison Univ, Dept Commun Sci & Disorders, Harrisonburg, VA 22807 USA.
RP Feng, X (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Otolaryngol, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM xfeng@wakehealth.edu
OI Ludlow, Christy/0000-0002-2015-6171
FU National Institute of Neurological Disorders and Stroke; National
Institute of Arthritis and Musculoskeletal and Skin Diseases; National
Institutes of Health; Department of Otolaryngology, Wake Forest
University School of Medicine; [U54 NS065701]
FX This work was supported by the Intramural Program of the National
Institute of Neurological Disorders and Stroke, National Institute of
Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, and by the Department of Otolaryngology, Wake Forest University
School of Medicine.; Dr. Ludlow is a consultant for Passy Muir Inc. and
Alfred Mann Foundation, and receives support from U54 NS065701. The
authors have no other funding, financial relationships, or conflicts of
interest to disclose.
NR 32
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD MAY
PY 2012
VL 122
IS 5
BP 1093
EP 1098
DI 10.1002/lary.23218
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 927XY
UT WOS:000302945100028
PM 22374515
ER
PT J
AU Shaked, A
Feng, S
Punch, J
Reyes, J
Levitsky, J
Klintmalm, G
Zimmerman, M
DesMarais, M
Kopeskie, H
Priore, A
Bridges, N
Sayre, P
AF Shaked, A.
Feng, S.
Punch, J.
Reyes, J.
Levitsky, J.
Klintmalm, G.
Zimmerman, M.
DesMarais, M.
Kopeskie, H.
Priore, A.
Bridges, N.
Sayre, P.
TI Initial Outcomes of ITN030ST: Early Post-Liver Transplant
Immunosuppression Withdrawal
SO LIVER TRANSPLANTATION
LA English
DT Meeting Abstract
CT 18th Annual International Congress on ILTS
CY MAY 16-19, 2012
CL San Francisco, CA
SP ILTS
C1 [Shaked, A.] UPenn, Philadelphia, PA USA.
[Feng, S.; DesMarais, M.; Sayre, P.] UCSF, San Francisco, CA USA.
[Punch, J.] U Michigan, Ann Arbor, MI USA.
[Reyes, J.] U Washington, Seattle, WA USA.
[Levitsky, J.] Northwestern, Chicago, IL USA.
[Klintmalm, G.] Baylor, Dallas, TX USA.
[Zimmerman, M.] U Colorado, Denver, CO USA.
[Kopeskie, H.] RhoFed, Chapel Hill, NC USA.
[Priore, A.; Bridges, N.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD MAY
PY 2012
VL 18
SU 1
BP S106
EP S106
PG 1
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 929EE
UT WOS:000303043200083
ER
PT J
AU Ramesh, A
Small, ST
Kloos, ZA
Kazura, JW
Nutman, TB
Serre, D
Zimmerman, PA
AF Ramesh, Akshaya
Small, Scott T.
Kloos, Zachary A.
Kazura, James W.
Nutman, Thomas B.
Serre, David
Zimmerman, Peter A.
TI The complete mitochondrial genome sequence of the filarial nematode
Wuchereria bancrofti from three geographic isolates provides evidence of
complex demographic history
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Filariasis; Mitochondrial genome; DNA sequence; Phylogeny
ID RNA SECONDARY STRUCTURE; ELONGATION-FACTOR TU; PHYLOGENETIC ANALYSIS;
POPULATION-GENETICS; PARASITIC NEMATODES; NECATOR-AMERICANUS; CODON
USAGE; TRNASCAN-SE; DNA; PROGRAM
AB Mitochondrial (mt) genome sequences have enabled comparison of population genetics and evolution for numerous free-living and parasitic nematodes. Here we define the complete mt genome of Wuchereria bancrofti through analysis of isolates from Papua New Guinea, India and West Africa. Sequences were assembled for each isolate and annotated with reference to the mt genome sequence for Brugia malayi. The length of the W. bancrofti mt genome is approximately 13,637 nucleotides, contains 2 ribosomal RNAs (rrns), 22 transfer RNAs (trns), 12 protein-coding genes, and is characterized by a 74.6% AT content. The W. bancrofti mt gene order is identical to that reported for Onchocerca volvulus, Dirofilaria immitis, Setaria digitata and B. malayi. In addition to using translational start codons identified previously in the mt protein-coding genes of other filarial nematodes, W. bancrofti appears to be unique in using TGT as a translational start codon. Similarly, use of incomplete stop codons in mt protein-coding genes appears to be more common in W. bancrofti than in other human filarial parasites. The complete mt genome sequence reported here provides new genetic markers for investigating phylogenetic and geographic relationships between isolates, and assessing population diversity within endemic regions. The sequence polymorphism enables new strategies to monitor the progress of public health interventions to control and eliminate this important human parasite. We illustrate the utility of this sequence and single nucleotide polymorphisms by inferring the divergence times between the three W. bancrofti isolates, suggesting predictions into their origin and migration. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Ramesh, Akshaya; Small, Scott T.; Kloos, Zachary A.; Kazura, James W.; Zimmerman, Peter A.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Ramesh, Akshaya; Zimmerman, Peter A.] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA.
[Nutman, Thomas B.] NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Serre, David] Cleveland Clin, Genom Med Inst, Cleveland, OH 44195 USA.
RP Zimmerman, PA (reprint author), Case Western Reserve Univ, Ctr Global Hlth & Dis, Biomed Res Bldg,Room E426,2109 Adelbert Rd, Cleveland, OH 44106 USA.
EM paz@case.edu
OI Zimmerman, Peter/0000-0002-5349-4513
FU National Institutes of Health [AI065717]; Fogarty International Center
[TW007872, AI007024]; Division of Intramural Research (DIR) of the
National Institute of Allergy and Infectious Diseases (NIAID)
FX We thank study participants in PNG, as well as Dr. S. Bennuru for his
assistance with primer design. We also thank Dr. R. Gutell for
generating the rrnS and rrnL secondary structure diagrams (Fig. S3a-c)
and the Broad Institute for access to the W. bancrofti mtDNA sequence
data. We acknowledge financial support for this study through grants
from the National Institutes of Health (AI065717 to J.W. Kazura and P.A.
Zimmerman), the Fogarty International Center (Ecology of Infectious
Diseases, TW007872 to P.A. Zimmerman, a T32 Postdoctoral Fellowship to
S.T. Small (AI007024), and support from the Division of Intramural
Research (DIR) of the National Institute of Allergy and Infectious
Diseases (NIAID) to Dr. T.B. Nutman.
NR 57
TC 20
Z9 20
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD MAY
PY 2012
VL 183
IS 1
BP 32
EP 41
DI 10.1016/j.molbiopara.2012.01.004
PG 10
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 929OL
UT WOS:000303075100005
PM 22326389
ER
PT J
AU Luo, JF
Gao, YT
Chow, WH
Shu, XO
Li, HL
Yang, G
Cai, QY
Li, GL
Rothman, N
Cai, H
Shrubsole, MJ
Franke, AA
Zheng, W
Dai, Q
AF Luo, Jianfeng
Gao, Yu-Tang
Chow, Wong-Ho
Shu, Xiao-ou
Li, Honglan
Yang, Gong
Cai, Qiuyin
Li, Guoliang
Rothman, Nathaniel
Cai, Hui
Shrubsole, Martha J.
Franke, Adrian A.
Zheng, Wei
Dai, Qi
TI Urinary polyphenols, glutathione S-transferases copy number variation,
and breast cancer risk: Results from the Shanghai women's health study
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE tea polyphenols; flavonol; flavanol; genomic polymorphism; interaction
ID GREEN TEA; GENETIC POLYMORPHISMS; COLORECTAL-CANCER; DIETARY
ISOTHIOCYANATES; MOLECULAR EPIDEMIOLOGY; GSTP1 POLYMORPHISMS; AMERICAN
WOMEN; BLACK TEA; GSTM1; GSTT1
AB In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione S-transferases (GSTs), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk. We conducted a study of 352 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 4070?yr at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real-time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes. Urinary excretion of flavonols and flavanols, particularly EGC (P?=?0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a P-value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol. The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer. Mol. Carcinog. (c) 2011 Wiley Periodicals, Inc.
C1 [Dai, Qi] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Sch Med,Inst Med & Publ Hl, Nashville, TN 37203 USA.
[Luo, Jianfeng] Fudan Univ, Dept Hlth Stat & Social Med, Key Lab Publ Hlth Safety, Minist Educ,Sch Publ Hlth, Shanghai 200433, Peoples R China.
[Gao, Yu-Tang; Li, Honglan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Franke, Adrian A.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
RP Dai, Q (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Sch Med,Inst Med & Publ Hl, 6th Floor,Suite 600,2525 W End Ave, Nashville, TN 37203 USA.
RI Shrubsole, Martha/K-5052-2015; LI, GUOLIANG/E-7359-2015
OI Shrubsole, Martha/0000-0002-5591-7575; LI, GUOLIANG/0000-0001-8493-4684
FU USPHS [R01CA106591, R37CA70867]; NIH [N02 CP1101066, S10 RR020890-01]
FX This study was supported by USPHS grant R01CA106591 and R37CA70867.
Biological sample collection in the parent study was supported in part
by NIH intramural program (N02 CP1101066) for the parent study. The
authors thank Laurie Custer for the skillful performance of LC/MS
assays. We also acknowledge the support by NIH grant S10 RR020890-01.
NR 54
TC 8
Z9 9
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD MAY
PY 2012
VL 51
IS 5
BP 379
EP 388
DI 10.1002/mc.20799
PG 10
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 923MI
UT WOS:000302623000002
PM 21557334
ER
PT J
AU Rakocevic, G
Floeter, MK
AF Rakocevic, Goran
Floeter, Mary Kay
TI Autoimmune stiff person syndrome and related myelopathies: Understanding
of electrophysiological and immunological processes
SO MUSCLE & NERVE
LA English
DT Review
DE anti-GAD antibodies; autoimmunity; GABA; paraneoplastic disorders; stiff
person syndrome
ID GLUTAMIC-ACID-DECARBOXYLASE; PARANEOPLASTIC NEUROLOGICAL SYNDROMES;
ANTI-GAD ANTIBODIES; DEPENDENT DIABETES-MELLITUS; CEREBELLAR GABAERGIC
TRANSMISSION; MATERNAL PASSIVE TRANSFER; PLACEBO-CONTROLLED TRIAL; CELL
LUNG-CARCINOMA; HUMAN MOTOR CORTEX; BREAST-CANCER
AB Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Impaired synaptic GABAergic inhibition resulting from intrathecal B-cellmediated clonal synthesis of autoantibodies against various presynaptic and synaptic proteins in the inhibitory neurons of the brain and spinal cord is believed to be an underlying pathogenic mechanism. SPS is most often idiopathic, but it can occur as a paraneoplastic condition. Despite evidence that anti-GAD and related autoantibodies impair GABA synthesis, the exact pathogenic mechanism of SPS is not fully elucidated. The strong association with several MHC-II alleles and improvement of symptoms with immune-modulating therapies support an autoimmune etiology of SPS. In this review, we discuss the clinical spectrum, neurophysiological mechanisms, and therapeutic options, including a rationale for agents that modulate B-cell function in SPS. Muscle Nerve, 2012
C1 [Rakocevic, Goran] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA.
[Floeter, Mary Kay] Natl Inst Neurol Disorders & Stroke, EMG Sect, NIH, Bethesda, MD USA.
RP Rakocevic, G (reprint author), Thomas Jefferson Univ, Dept Neurol, 900 Walnut St,Suite 200, Philadelphia, PA 19107 USA.
EM goran.rakocevic@jefferson.edu
FU National Institutes of Health, NINDS
FX This study was supported by a grant from the Intramural Research Program
of the National Institutes of Health, NINDS (to M.K.F.).
NR 165
TC 19
Z9 22
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD MAY
PY 2012
VL 45
IS 5
BP 623
EP 634
DI 10.1002/mus.23234
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 924WV
UT WOS:000302722900002
PM 22499087
ER
PT J
AU Shupp, JW
Petraitiene, R
Jaskille, AD
Pavlovich, AR
Matt, SE
Nguyen, DT
Kath, MA
Jeng, JC
Jordan, MH
Finkelman, M
Walsh, TJ
Shoham, S
AF Shupp, Jeffrey W.
Petraitiene, Ruta
Jaskille, Amin D.
Pavlovich, Anna R.
Matt, Sarah E.
Nguyen, Do T.
Kath, Melissa A.
Jeng, James C.
Jordan, Marion H.
Finkelman, Malcolm
Walsh, Thomas J.
Shoham, Shmuel
TI Early serum (1 -> 3)-beta-D-glucan levels in patients with burn injury
SO MYCOSES
LA English
DT Article
DE Diagnosis of candidemia; burn wound infection
ID INVASIVE FUNGAL-INFECTIONS; EARLY POSTBURN PERIOD; WOUND MANIPULATION;
DIAGNOSIS; GLUCAN; BLOOD; CANDIDIASIS; BACTEREMIA; ASSAY
AB Serum (1?3)-beta-D-glucan (BG) is increasingly used as diagnostic marker for invasive fungal infections. Exposure to gauze may lead to false-positive BG assays. The role of BG is unclear in thermally injured patients who frequently require extensive gauze coverage; therefore, we prospectively evaluated BG levels in burn-injured patients. Serum BG levels were measured in 18 burn patients immediately before application of the first dressing and 12 h after. Patients were stratified by extent of total body surface area (TBSA) requiring gauze coverage: <20%, 2039%, 4060% and >60%. BG levels were obtained from patients with non-burn trauma as controls. BG results were positive (>80 pg ml-1) in 9/18 (50%) patients at baseline and in 8/18 (44%) 12 h after application of the first dressing. BG levels were positive in 1/5 (20%) of patients with <20% TBSA requiring gauze and in 10/13 (77%) with =20% (P < 0.05). None of the control patients had positive BG at any time point and none of the patients had candidemia at baseline. Mean serum BG levels decreased (19.44 pg ml-1) after gauze placement. False-positive serum BG elevations are common in this patient population. Positivity correlates with extent of TBSA injured, but is not impacted by the gauze itself.
C1 [Shupp, Jeffrey W.; Jaskille, Amin D.; Pavlovich, Anna R.; Matt, Sarah E.; Kath, Melissa A.; Jeng, James C.; Jordan, Marion H.] Washington Hosp Ctr, Burn Ctr, Dept Surg, Washington, DC 20010 USA.
[Shupp, Jeffrey W.; Jaskille, Amin D.; Pavlovich, Anna R.; Matt, Sarah E.; Kath, Melissa A.; Jeng, James C.; Jordan, Marion H.; Shoham, Shmuel] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Nguyen, Do T.] Georgetown Univ, Sch Med, Washington, DC USA.
[Finkelman, Malcolm] Associates Cape Cod Inc, E Falmouth, MA USA.
[Petraitiene, Ruta; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Petraitiene, Ruta; Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Div Infect Dis, Dept Med,Weill Cornell Med Coll, New York, NY 10021 USA.
[Shoham, Shmuel] Washington Hosp Ctr, Infect Dis Sect, Dept Med, Washington, DC 20010 USA.
RP Shupp, JW (reprint author), 110 Irving St NW, Washington, DC 20010 USA.
EM jeffrey.w.shupp@medstar.net
NR 17
TC 1
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0933-7407
J9 MYCOSES
JI Mycoses
PD MAY
PY 2012
VL 55
IS 3
BP 224
EP 227
DI 10.1111/j.1439-0507.2011.02068.x
PG 4
WC Dermatology; Mycology
SC Dermatology; Mycology
GA 928PJ
UT WOS:000302994900017
PM 21771107
ER
PT J
AU Sengupta, I
Nadaud, PS
Helmus, JJ
Schwieters, CD
Jaroniec, CP
AF Sengupta, Ishita
Nadaud, Philippe S.
Helmus, Jonathan J.
Schwieters, Charles D.
Jaroniec, Christopher P.
TI Protein fold determined by paramagnetic magic-angle spinning solid-state
NMR spectroscopy
SO NATURE CHEMISTRY
LA English
DT Article
ID SITE-DIRECTED SPIN; RANGE STRUCTURAL RESTRAINTS;
NUCLEAR-MAGNETIC-RESONANCE; 3D STRUCTURE DETERMINATION; STAPHYLOCOCCAL
NUCLEASE; STRUCTURE REFINEMENT; DISTANCE RESTRAINTS; AMYLOID FIBRILS;
CHEMICAL-SHIFTS; RELAXATION
AB Biomacromolecules that are challenging for the usual structural techniques can be studied with atomic resolution by solid-state NMR spectroscopy. However, the paucity of distance restraints >5 angstrom, traditionally derived from measurements of magnetic dipole-dipole couplings between protein nuclei, is a major bottleneck that hampers such structure elucidation efforts. Here, we describe a general approach that enables the rapid determination of global protein fold in the solid phase via measurements of nuclear paramagnetic relaxation enhancements (PREs) in several analogues of the protein of interest containing covalently attached paramagnetic tags, without the use of conventional internuclear distance restraints. The method is demonstrated using six cysteine-EDTA-Cu2+ mutants of the 56-residue B1 immunoglobulin-binding domain of protein G, for which similar to 230 longitudinal backbone N-15 PREs corresponding to distances of similar to 10-20 angstrom were obtained. The mean protein fold determined in this manner agrees with the X-ray structure with a backbone atom root-mean-square deviation of 1.8 angstrom.
C1 [Sengupta, Ishita; Nadaud, Philippe S.; Helmus, Jonathan J.; Jaroniec, Christopher P.] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA.
[Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Jaroniec, CP (reprint author), Ohio State Univ, Dept Chem, 100 W 18th Ave, Columbus, OH 43210 USA.
EM jaroniec@chemistry.ohio-state.edu
RI Jaroniec, Christopher/A-4948-2008;
OI Jaroniec, Christopher/0000-0003-0364-2888
FU National Science Foundation [MCB-0745754]; National Institutes of Health
of the Center for Information Technology
FX This research was supported by the National Science Foundation (CAREER
award MCB-0745754 to C.P.J.). C.D.S. was supported by the National
Institutes of Health Intramural Research Program of the Center for
Information Technology. The GB1 plasmid was kindly provided by A.M.
Gronenborn.
NR 50
TC 47
Z9 47
U1 4
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1755-4330
J9 NAT CHEM
JI Nat. Chem.
PD MAY
PY 2012
VL 4
IS 5
BP 410
EP 417
DI 10.1038/NCHEM.1299
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 930BF
UT WOS:000303109700017
PM 22522262
ER
PT J
AU Denk, W
Briggman, KL
Helmstaedter, M
AF Denk, Winfried
Briggman, Kevin L.
Helmstaedter, Moritz
TI Structural neurobiology: missing link to a mechanistic understanding of
neural computation
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID SCANNING-ELECTRON-MICROSCOPY; WHOLE-CELL RECORDINGS; IN-VIVO;
FLUORESCENCE MICROSCOPY; CAENORHABDITIS-ELEGANS; NETWORK ACTIVITY;
NERVOUS-SYSTEM; NEURONS; SINGLE; BRAIN
AB High-resolution, comprehensive structural information is often the final arbiter between competing mechanistic models of biological processes, and can serve as inspiration for new hypotheses. In molecular biology, definitive structural data at atomic resolution are available for many macromolecules; however, information about the structure of the brain is much less complete, both in scope and resolution. Several technical developments over the past decade, such as serial block-face electron microscopy and trans-synaptic viral tracing, have made the structural biology of neural circuits conceivable: we may be able to obtain the structural information needed to reconstruct the network of cellular connections for large parts of, or even an entire, mouse brain within a decade or so. Given that the brain's algorithms are ultimately encoded by this network, knowing where all of these connections are should, at the very least, provide the data needed to distinguish between models of neural computation.
C1 [Denk, Winfried] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
[Briggman, Kevin L.] NINDS, Bethesda, MD 20892 USA.
[Helmstaedter, Moritz] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
RP Denk, W (reprint author), Max Planck Inst Med Res, Jahnstr 29, D-69120 Heidelberg, Germany.
EM denk@mpimf-heidelberg.mpg.de
RI denk, winfried/I-6627-2012
NR 84
TC 81
Z9 81
U1 3
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD MAY
PY 2012
VL 13
IS 5
BP 351
EP 358
DI 10.1038/nrn3169
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 929KC
UT WOS:000303059600013
PM 22353782
ER
PT J
AU Ibrahim, L
DiazGranados, N
Franco-Chaves, J
Brutsche, N
Henter, ID
Kronstein, P
Moaddel, R
Wainer, I
Luckenbaugh, DA
Manji, HK
Zarate, CA
AF Ibrahim, Lobna
DiazGranados, Nancy
Franco-Chaves, Jose
Brutsche, Nancy
Henter, Ioline D.
Kronstein, Phillip
Moaddel, Ruin
Wainer, Irving
Luckenbaugh, David A.
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI Course of Improvement in Depressive Symptoms to a Single Intravenous
Infusion of Ketamine vs Add-on Riluzole: Results from a 4-Week,
Double-Blind, Placebo-Controlled Study
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE antidepressant; depression; glutamate; ketamine; NMDA; riluzole
ID D-ASPARTATE ANTAGONIST; RESISTANT MAJOR DEPRESSION; MOOD DISORDERS;
RATING-SCALE; TRIAL; IDEATION; STATES
AB The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single-ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of >= 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n = 21) or placebo (n = 21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE = 2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone. Neuropsychopharmacology (2012) 37, 1526-1533; doi: 10.1038/npp.2011.338; published online 1 February 2012
C1 [Ibrahim, Lobna; DiazGranados, Nancy; Franco-Chaves, Jose; Brutsche, Nancy; Kronstein, Phillip; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[DiazGranados, Nancy] Univ Texas Hlth Sci Ctr, San Antonio, TX USA.
[Henter, Ioline D.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kronstein, Phillip] US FDA, Silver Spring, MD USA.
[Moaddel, Ruin; Wainer, Irving] NIA, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH, 10 Ctr Dr,CRC,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
(NIMH-NIH)
FX This study was supported in part by the Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health
(NIMH-NIH). The author(s) declare that, except for income received from
our primary employer, no financial support or compensation has been
received from any individual or corporate entity over the past 3 years
for research or professional service and there are no personal financial
holdings that could be perceived as constituting a potential conflict of
interest. A patent application for the use of ketamine in depression has
been submitted listing Drs Zarate and Manji among the inventors; they
have assigned their rights on the patent to the U. S. government, but
will share a percentage of any royalties that may be received by the
government.
NR 33
TC 115
Z9 117
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2012
VL 37
IS 6
BP 1526
EP 1533
DI 10.1038/npp.2011.338
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 927GY
UT WOS:000302896600019
PM 22298121
ER
PT J
AU Camp, MC
MacPherson, KP
Lederle, L
Graybeal, C
Gaburro, S
DeBrouse, LM
Ihne, JL
Bravo, JA
O'Connor, RM
Ciocchi, S
Wellman, CL
Luthi, A
Cryan, JF
Singewald, N
Holmes, A
AF Camp, Marguerite C.
MacPherson, Kathryn P.
Lederle, Lauren
Graybeal, Carolyn
Gaburro, Stefano
DeBrouse, Lauren M.
Ihne, Jessica L.
Bravo, Javier A.
O'Connor, Richard M.
Ciocchi, Stephane
Wellman, Cara L.
Luethi, Andreas
Cryan, John F.
Singewald, Nicolas
Holmes, Andrew
TI Genetic Strain Differences in Learned Fear Inhibition Associated with
Variation in Neuroendocrine, Autonomic, and Amygdala Dendritic
Phenotypes
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE gene; vmPFC; anxiety; depression; PTSD; infralimbic; stress
ID POSTTRAUMATIC-STRESS-DISORDER; DEPRESSIVE-LIKE BEHAVIOR;
HEART-RATE-VARIABILITY; PREFRONTAL CORTEX; RATE DYNAMICS; ADRENAL AXIS;
MICE; EXTINCTION; RECEPTOR; ANXIETY
AB Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors. Here, we performed a comprehensive examination of the extinction-impaired 129S1/SvImJ (S1) inbred mouse strain for multiple behavioral, autonomic, neuroendocrine, and corticolimbic neuronal morphology phenotypes. We found that S1 exhibited fear overgeneralization to ambiguous contexts and cues, impaired context extinction and impaired safety learning, relative to the (good-extinguishing) C57BL/6J (B6) strain. Fear overgeneralization and impaired extinction was rescued by treatment with the front-line anxiety medication fluoxetine. Telemetric measurement of electrocardiogram signals demonstrated autonomic disturbances in S1 including poor recovery of fear-induced suppression of heart rate variability. S1 with a history of chronic restraint stress displayed an attenuated corticosterone (CORT) response to a novel, swim stressor. Conversely, previously stress-naive S1 showed exaggerated CORT responses to acute restraint stress or extinction training, insensitivity to dexamethasone challenge, and reduced hippocampal CA3 glucocorticoid receptor mRNA, suggesting downregulation of negative feedback control of the hypothalamic-pituitary-adrenal axis. Analysis of neuronal morphology in key neural nodes within the fear and extinction circuit revealed enlarged dendritic arbors in basolateral amygdala neurons in S1, but normal infralimbic cortex and prelimbic cortex dendritic arborization. Collectively, these data provide convergent support for the utility of the S1 strain as a tractable model for elucidating the neural, molecular and genetic basis of persistent, excessive fear. Neuropsychopharmacology (2012) 37, 1534-1547; doi: 10.1038/npp.2011.340; published online 15 February 2012
C1 [Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD 21044 USA.
[Gaburro, Stefano; Singewald, Nicolas] Univ Innsbruck, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria.
[Bravo, Javier A.; Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland.
[O'Connor, Richard M.; Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol & Therapeut, Cork, Ireland.
[Ciocchi, Stephane; Luethi, Andreas] Friedrich Miescher Inst, CH-4002 Basel, Switzerland.
[Wellman, Cara L.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
RP Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Bethesda, MD 21044 USA.
EM holmesan@mail.nih.gov
RI Cryan, John/A-6950-2013
OI O'Connor, Richard/0000-0001-5351-8856; Reed,
Jessica/0000-0003-0550-7284; Cryan, John/0000-0001-5887-2723
FU NIAAA; Austrian Science Fund [F4410-B19]
FX We thank Daniela Pollak, Fred Helmstetter, and O Stiedl for valuable
discussions and methods advice, and Heather Cameron for RIA equipment.
This study was supported by the NIAAA Intramural Research Program and
the Austrian Science Fund (F4410-B19).
NR 62
TC 38
Z9 38
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2012
VL 37
IS 6
BP 1534
EP 1547
DI 10.1038/npp.2011.340
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 927GY
UT WOS:000302896600020
PM 22334122
ER
PT J
AU Budde, MD
Gold, E
Jordan, EK
Smith-Brown, M
Frank, JA
AF Budde, Matthew D.
Gold, Eric
Jordan, E. Kay
Smith-Brown, Melissa
Frank, Joseph A.
TI Phase contrast MRI is an early marker of micrometastatic breast cancer
development in the rat brain
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRI; phase contrast; vascular remodeling; brain metastasis; vessel
co-option; ferumoxides
ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; METASTASIS;
TUMORS; ANGIOGENESIS; HYPOXIA; MODEL; CELL; OXYGENATION
AB The early growth of micrometastatic breast cancer in the brain often occurs through vessel co-option and is independent of angiogenesis. Remodeling of the existing vasculature is an important step in the evolution of co-opting micrometastases into angiogenesis-dependent solid tumor masses. The purpose of this study was to determine whether phase contrast MRI, an intrinsic source of contrast exquisitely sensitive to the magnetic susceptibility properties of deoxygenated hemoglobin, could detect vascular changes occurring independent of angiogenesis in a rat model of breast cancer metastases to the brain. Twelve nude rats were administered 106 MDA-MB-231BRL brain-seeking breast cancer cells through intracardiac injection. Serial, multiparametric MRI of the brain was performed weekly until metastatic disease was detected. The results demonstrated that images of the signal phase (area under the receiver operating characteristic curve, 0.97) were more sensitive than T2* gradient echo magnitude images (area under the receiver operating characteristic curve, 0.73) to metastatic brain lesions. The difference between the two techniques was probably the result of the confounding effects of edema on the magnitude of the signal. A region of interest analysis revealed that vascular abnormalities detected with phase contrast MRI preceded tumor permeability measured with contrast-enhanced MRI by 12?weeks. Tumor size was correlated with permeability (R2?=?0.23, p?0.01), but phase contrast was independent of tumor size (R2?=?0.03). Histopathologic analysis demonstrated that capillary endothelial cells co-opted by tumor cells were significantly enlarged, but less dense, relative to the normal brain vasculature. Although co-opted vessels were vascular endothelial growth factor-negative, vessels within larger tumor masses were vascular endothelial growth factor-positive. In conclusion, phase contrast MRI is believed to be sensitive to vascular remodeling in co-opting brain tumor metastases independent of sprouting angiogenesis, and may therefore aid in preclinical studies of angiogenic-independent tumors or in the monitoring of continued tumor growth following anti-angiogenic therapy. Published 2011. This article is a US Government work and is in the public domain in the USA.
C1 [Budde, Matthew D.; Gold, Eric; Jordan, E. Kay; Smith-Brown, Melissa; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Budde, MD (reprint author), 9000 Rockville Pike,Bldg 10,B1N256, Bethesda, MD 20892 USA.
EM buddem@mail.nih.gov
FU Clinical Center at the National Institutes of Health, Bethesda, MD, USA
FX We thank Dr Diane Palmieri for providing the MDA-MB-231BRL cells. This
work was supported by the Intramural Research Program of the Clinical
Center at the National Institutes of Health, Bethesda, MD, USA.
NR 57
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD MAY
PY 2012
VL 25
IS 5
BP 726
EP 736
DI 10.1002/nbm.1786
PG 11
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 923KG
UT WOS:000302617600004
PM 21954124
ER
PT J
AU Zhang, J
Kim, S
Grewal, J
Albert, PS
AF Zhang, Jun
Kim, Sungduk
Grewal, Jagteshwar
Albert, Paul S.
TI Predicting large fetuses at birth: do multiple ultrasound examinations
and longitudinal statistical modelling improve prediction?
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE birthweight; fetal weight; large-for-gestational age; macrosomia;
prediction
ID FETAL WEIGHT; SINGLE; GROWTH; TERM
AB Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant size was classified as large-for-gestational age (LGA, >90th centile) and macrosomia (>4000 g) or not. We used a longitudinal random effects model with quadratic fixed and random effects to predict term LGA and macrosomia at birth. Receiver-operator curves and mean-squared error were used to measure accuracy of the prediction. Ultrasound examination around 37 weeks had the best accuracy in predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations at earlier gestations did not improve the accuracy. Adjusting for maternal characteristics had limited impact on the accuracy of prediction. Thus, a single ultrasound examination at late gestation close to birth is the simplest method currently available to predict LGA and macrosomia.
C1 [Albert, Paul S.] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, MOE, Xinhua Hosp, Shanghai 200030, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Childrens Environm Hlth, Xinhua Hosp, Shanghai 200030, Peoples R China.
[Zhang, Jun] Sch Publ Hlth, Shanghai, Peoples R China.
RP Albert, PS (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
EM albertp@mail.nih.gov
OI Grewal, Jagteshwar/0000-0002-0141-4876
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This research was supported in part by the intramural research programme
of Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 20
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAY
PY 2012
VL 26
IS 3
BP 199
EP 207
DI 10.1111/j.1365-3016.2012.01261.x
PG 9
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 921IL
UT WOS:000302471200004
PM 22471679
ER
PT J
AU Kharrazi, M
Pearl, M
Yang, J
DeLorenze, GN
Bean, CJ
Callaghan, WM
Grant, A
Lackritz, E
Romero, R
Satten, GA
Simhan, H
Torres, AR
Westover, JB
Yolken, R
Williamson, DM
AF Kharrazi, Martin
Pearl, Michelle
Yang, Juan
DeLorenze, Gerald N.
Bean, Christopher J.
Callaghan, William M.
Grant, Althea
Lackritz, Eve
Romero, Roberto
Satten, Glen A.
Simhan, Hyagriv
Torres, Anthony R.
Westover, Jonna B.
Yolken, Robert
Williamson, Dhelia M.
TI California Very Preterm Birth Study: design and characteristics of the
population- and biospecimen bank-based nested case-control study
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE Study design; California Very Preterm Birth Study
ID TUMOR-NECROSIS-FACTOR; SINGLE-NUCLEOTIDE POLYMORPHISMS; CYTOKINE GENE
POLYMORPHISMS; PROGESTERONE-RECEPTOR GENE; THAN-G POLYMORPHISM;
FACTOR-ALPHA GENE; PREMATURE-RUPTURE; AFRICAN-AMERICANS; FETAL
MEMBRANES; THROMBOPHILIC POLYMORPHISMS
AB Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from state-wide prenatal and newborn screening, 1100 VPTB cases and 796 control mother-infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.
C1 [Kharrazi, Martin] Calif Dept Publ Hlth, Program Res & Demonstrat Sect, Genet Dis Screening Program, Richmond, CA 94804 USA.
[Pearl, Michelle; Yang, Juan] Sequoia Fdn, La Jolla, CA USA.
[DeLorenze, Gerald N.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Bean, Christopher J.; Grant, Althea] Ctr Dis Control & Prevent, Div Blood Disorders, Atlanta, GA USA.
[Callaghan, William M.; Lackritz, Eve; Satten, Glen A.; Williamson, Dhelia M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI USA.
[Simhan, Hyagriv] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Torres, Anthony R.; Westover, Jonna B.] Utah State Univ, Ctr Persons Disabil, Logan, UT 84322 USA.
[Yolken, Robert] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Kharrazi, M (reprint author), Calif Dept Publ Hlth, Program Res & Demonstrat Sect, Genet Dis Screening Program, 850 Marina Bay Pkwy,Room F175,Mail Stop 8200, Richmond, CA 94804 USA.
EM marty.kharrazi@cdph.ca.gov
OI Satten, Glen/0000-0001-7275-5371
FU Centers for Disease Control and Prevention; March of Dimes Birth Defects
Foundation [21-FY05-1248]; Tobacco Related Disease Research Program
[8RT-0115]
FX This study was funded in part by the Centers for Disease Control and
Prevention and the March of Dimes Birth Defects Foundation (project
#21-FY05-1248). Project Baby's Breath, which created the initial
prenatal specimen bank used by this study, was funded by the Tobacco
Related Disease Research Program (grant #8RT-0115) (Drs Martin Kharrazi
and Gerald N. DeLorenze, Co-PIs). Drs John Harris and Gary Shaw were
responsible for the creation of the second prenatal specimen bank. Dr
George Cunningham was responsible for the creation of the newborn
specimen bank. California Birth Defects Monitoring Program staff
(Jennifer Nicholson, Brandy Stephenson, Butch Arciaga and Cori DeTarr)
conducted hospital abstraction under the supervision of Barbara
Warmerdam. Steve Graham and Oren Bergman conducted record linkage of the
screening and vital records data files. Megan Wier contributed to the
study design and the conduct of the study in its early phases. Angela
DiLaura and Marissa Root assisted with project coordination. Dr Michael
S. Kramer gave valuable input on the early development of the
abstraction form and F. Carol Bruce gave feedback on the conduct of the
study.
NR 86
TC 6
Z9 6
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAY
PY 2012
VL 26
IS 3
BP 250
EP 263
DI 10.1111/j.1365-3016.2011.01252.x
PG 14
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 921IL
UT WOS:000302471200009
PM 22471684
ER
PT J
AU Ito, T
Igarashi, H
Jensen, RT
AF Ito, Tetsuhide
Igarashi, Hisato
Jensen, Robert T.
TI Serum Pancreastatin The Long Sought Universal, Sensitive, Specific Tumor
Marker for Neuroendocrine Tumors?
SO PANCREAS
LA English
DT Editorial Material
ID CHROMOGRANIN-A; PEPTIDES; GASTRINOMAS; PROHORMONE; SURVIVAL; THERAPY;
PLASMA
C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20817 USA.
[Ito, Tetsuhide; Igarashi, Hisato] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20817 USA.
EM robertj@bdg10.niddk.nih.gov
FU Intramural NIH HHS [ZIA DK053200-19, Z99 DK999999]
NR 21
TC 16
Z9 19
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAY
PY 2012
VL 41
IS 4
BP 505
EP 507
DI 10.1097/MPA.0b013e318249a92a
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 928VD
UT WOS:000303014100001
PM 22504376
ER
PT J
AU Zhang, YH
Miura, K
Li, J
Tullo, G
Zhu, F
Hong, LX
Lin, TL
Su, XZ
Long, C
AF Zhang, Yanhui
Miura, Kazutoyo
Li, Jian
Tullo, Gregory
Zhu, Feng
Hong, Lingxian
Lin, Tianlong
Su, Xin-zhuan
Long, Carole
TI Macrophage migration inhibitory factor homolog from Plasmodium yoelii
modulates monocyte recruitment and activation in spleen during infection
SO PARASITOLOGY RESEARCH
LA English
DT Article
ID FACTOR MIF; FALCIPARUM-MALARIA; INDUCED ARTHRITIS; EXPRESSION; HEMOZOIN;
ANTIGEN; ANEMIA; CELLS; GLUCOCORTICOIDS; PHAGOCYTOSIS
AB Macrophage migration inhibitory factor (MIF) has been shown to be involved in the pathogenesis of severe malaria. Malaria parasites express an MIF homolog that may play a role in regulating host immune responses, and a recent study showed that overexpression of MIF reduced parasitemia in a mouse malaria model. Another recent study showed migration of monocytes to the spleen contributed to the control of blood stage infection. However, there are few papers describing the effect of MIF on monocyte recruitment/activation during the infection. We generated recombinant Plasmodium yoelii MIF (rPyMIF) and investigated its function on purified mouse CD11b(+) cells in vitro and monocyte responses in vivo. The result shows that rPyMIF protein bound to mouse CD11b(+) cells and inhibited their random migration in vitro. On the other hand, rPyMIF did not induce cytokine release from the cells directly or modulate lipopolysaccharide-induced cytokine release. Mice immunized with rPyMIF showed transient but significantly lower parasitemia than the control mice at day 3 after lethal Py17XL challenge. The total number of CD11b(+) cells in the spleens was significantly higher in rPyMIF-immunized group. Further investigation revealed that there were significantly higher numbers of recruited and activated monocytes in the spleens of rPyMIF immunization group on day 3. These results indicate that PyMIF potentially modulates monocyte recruitment and activation during infection of P. yoelii erythrocytic stages.
C1 [Zhang, Yanhui; Miura, Kazutoyo; Li, Jian; Tullo, Gregory; Su, Xin-zhuan; Long, Carole] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Yanhui; Li, Jian; Zhu, Feng; Hong, Lingxian; Su, Xin-zhuan] Xiamen Univ, State Key Lab Stress Cell Biol, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China.
[Lin, Tianlong] Fujian Acad Agr Sci, Fuzhou 350002, Fujian, Peoples R China.
RP Miura, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kmiura@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Basic
Research Program of China (973 Program) [2007CB513103]; Science Planning
Program of Fujian Province [2010 J1008]; 111 Project of Education of
China [B06016]
FX We thank Lubin Jiang and Cecilia Huaman for their technical help and the
animal facility in NIH Twinbrook 3 for taking care of the mice. We also
thank intramural editor Brenda Rae Marshall for editorial assistance.
This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and by grants from
the National Basic Research Program of China (973 Program) 2007CB513103,
from the Science Planning Program of Fujian Province (2010 J1008), and
from 111 Project of Education of China (no. B06016).
NR 31
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0932-0113
J9 PARASITOL RES
JI Parasitol. Res.
PD MAY
PY 2012
VL 110
IS 5
BP 1755
EP 1763
DI 10.1007/s00436-011-2696-6
PG 9
WC Parasitology
SC Parasitology
GA 926ES
UT WOS:000302814700021
PM 22015474
ER
PT J
AU Diesner, SC
Forster-Waldl, E
Olivera, A
Pollak, A
Jensen-Jarolim, E
Untersmayr, E
AF Diesner, Susanne C.
Foerster-Waldl, Elisabeth
Olivera, Ana
Pollak, Arnold
Jensen-Jarolim, Erika
Untersmayr, Eva
TI Perspectives on immunomodulation early in life
SO PEDIATRIC ALLERGY AND IMMUNOLOGY
LA English
DT Review
DE food allergy; immunomodulation; infection; newborns; sphingolipid; Th2;
Toll-like receptor
ID RESPIRATORY SYNCYTIAL VIRUS; INTESTINAL EPITHELIAL-CELLS; NEONATAL
DENDRITIC CELLS; SPHINGOSINE KINASE 1; CPG OLIGODEOXYNUCLEOTIDES;
IMMUNE-RESPONSES; ALLERGIC DISEASE; INNATE IMMUNITY; AIRWAY
INFLAMMATION; CORD BLOOD
AB The immune system early in life is characterized by immature activation and function of immune cells and a preponderance of Th2 cytokines. Together with other factors such as genetics and epigenetics, these immature immune responses might prone newborns susceptible to severe infections as well as allergic diseases. Immunomodulation therapy may have potential as therapeutic strategy against those disorders and might have implication in early-life interventions in the future. In this review, we will focus on two immunomodulatory substance classes, Toll-like receptor (TLR) ligands and sphingolipids, which are the focus of extensive research to date. Both TLRs and sphingolipid receptors have a very distinct distribution pattern and function on immune cells. Therefore, they can potentially modulate and balance immune responses, which might be in particular beneficial for the immaturity of the immune response early in life.
C1 [Diesner, Susanne C.; Jensen-Jarolim, Erika; Untersmayr, Eva] Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria.
[Diesner, Susanne C.; Foerster-Waldl, Elisabeth; Pollak, Arnold] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria.
[Olivera, Ana] NIAMS, Immunogenet Mol Lab, NIH, Bethesda, MD USA.
[Jensen-Jarolim, Erika] Med Univ Vienna, Messerli Res Inst, Vet Univ Vienna, A-1090 Vienna, Austria.
[Jensen-Jarolim, Erika] Univ Vienna, Vienna, Austria.
RP Untersmayr, E (reprint author), Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Waehringer Guertel 18-20,E3Q, A-1090 Vienna, Austria.
EM eva.untersmayr@meduniwien.ac.at
FU Austrian Science fund [P21884, P21577]; OeNB [13071]
FX This work is supported by the Austrian Science fund projects P21884 and
P21577 and the OeNB project 13071.
NR 111
TC 12
Z9 13
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0905-6157
EI 1399-3038
J9 PEDIAT ALLERG IMM-UK
JI Pediatr. Allergy Immunol.
PD MAY
PY 2012
VL 23
IS 3
BP 210
EP 223
DI 10.1111/j.1399-3038.2011.01259.x
PG 14
WC Allergy; Immunology; Pediatrics
SC Allergy; Immunology; Pediatrics
GA 927UA
UT WOS:000302934400002
PM 22299601
ER
PT J
AU Tildesley, MJ
Smith, G
Keeling, MJ
AF Tildesley, Michael J.
Smith, Gary
Keeling, Matt J.
TI Modeling the spread and control of foot-and-mouth disease in
Pennsylvania following its discovery and options for control
SO PREVENTIVE VETERINARY MEDICINE
LA English
DT Article
DE Foot and mouth disease; Spatial model; USA; Culling; Vaccination
ID H5N1 AVIAN INFLUENZA; 2001 UK FOOT; GREAT-BRITAIN; VACCINATION
STRATEGIES; NATURAL AEROSOLS; POULTRY FLOCK; FMD EPIDEMIC; OUTBREAK;
TRANSMISSION; VIRUS
AB In this paper, we simulate outbreaks of foot-and-mouth disease in the Commonwealth of Pennsylvania, USA - after the introduction of a state-wide movement ban - as they might unfold in the presence of mitigation strategies. We have adapted a model previously used to investigate FMD control policies in the UK to examine the potential for disease spread given an infection seeded in each county in Pennsylvania. The results are highly dependent upon the county of introduction and the spatial scale of transmission. Should the transmission kernel be identical to that for the UK, the epidemic impact is limited to fewer than 20 premises, regardless of the county of introduction. However, for wider kernels where infection can spread further, outbreaks seeded in or near the county with highest density of premises and animals result in large epidemics (>150 premises). Ring culling and vaccination reduce epidemic size, with the optimal radius of the rings being dependent upon the county of introduction. Should the kernel width exceed a given county-dependent threshold, ring culling is unable to control the epidemic. We find that a vaccinate-to-live policy is generally preferred to ring culling (in terms of reducing the overall number of premises culled), indicating that well-targeted control can dramatically reduce the risk of large scale outbreaks of foot-and-mouth disease occurring in Pennsylvania. (c) 2011 Elsevier B.V. All rights reserved.
C1 [Tildesley, Michael J.] Univ Warwick, Ctr Complex Sci, Coventry CV4 7AL, W Midlands, England.
[Tildesley, Michael J.] US Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Smith, Gary] Univ Penn, Sch Vet Med, New Bolton Ctr, Kennett Sq, PA 19348 USA.
[Keeling, Matt J.] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England.
RP Tildesley, MJ (reprint author), Univ Warwick, Ctr Complex Sci, Zeeman Bldg, Coventry CV4 7AL, W Midlands, England.
EM M.J.Tildesley@warwick.ac.uk
RI Keeling, Matt/J-9280-2012;
OI Keeling, Matt/0000-0003-4639-4765
FU Directorate of Science and Technology, U.S. Department of Homeland
Security, Chemical/Biological Division; National Institute of General
Medical Sciences [5U01GM-076426]; Science and Technology Directorate,
Department of Homeland Security [ST-108-000017]
FX This work was made possible by funding from the Research and Policy for
Infectious Disease Dynamics (RAPIDD) Program, Directorate of Science and
Technology, U.S. Department of Homeland Security, Chemical/Biological
Division, by award number 5U01GM-076426 from the National Institute of
General Medical Sciences and by the Foreign Animal Disease Modeling
program of the Science and Technology Directorate, Department of
Homeland Security (grant ST-108-000017). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of General Medical Sciences,
the National Institutes of Health or the Department of Homeland
Security.
NR 61
TC 6
Z9 7
U1 2
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-5877
EI 1873-1716
J9 PREV VET MED
JI Prev. Vet. Med.
PD MAY 1
PY 2012
VL 104
IS 3-4
BP 224
EP 239
DI 10.1016/j.prevetmed.2011.11.007
PG 16
WC Veterinary Sciences
SC Veterinary Sciences
GA 929AF
UT WOS:000303032900005
PM 22169708
ER
PT J
AU Knowles, MR
Leigh, MW
Carson, JL
Davis, SD
Dell, SD
Ferkol, TW
Olivier, KN
Sagel, SD
Rosenfeld, M
Burns, KA
Minnix, SL
Armstrong, MC
Lori, A
Hazucha, MJ
Loges, NT
Olbrich, H
Becker-Heck, A
Schmidts, M
Werner, C
Omran, H
Zariwala, MA
AF Knowles, Michael R.
Leigh, Margaret W.
Carson, Johnny L.
Davis, Stephanie D.
Dell, Sharon D.
Ferkol, Thomas W.
Olivier, Kenneth N.
Sagel, Scott D.
Rosenfeld, Margaret
Burns, Kimberlie A.
Minnix, Susan L.
Armstrong, Michael C.
Lori, Adriana
Hazucha, Milan J.
Loges, Niki T.
Olbrich, Heike
Becker-Heck, Anita
Schmidts, Miriam
Werner, Claudius
Omran, Heymut
Zariwala, Maimoona A.
CA Genetic Disorders Mucociliary
TI Mutations of DNAH11 in patients with primary ciliary dyskinesia with
normal ciliary ultrastructure
SO THORAX
LA English
DT Article
ID DYNEIN ARM DEFECTS; HEAVY-CHAIN; CHLAMYDOMONAS FLAGELLA; SITUS-INVERSUS;
GENE; ASYMMETRY; DOMAIN; DNAI1; MUTANT; INNER
AB Rationale Primary ciliary dyskinesia (PCD) is an autosomal recessive, genetically heterogeneous disorder characterised by oto-sino-pulmonary disease and situs abnormalities (Kartagener syndrome) due to abnormal structure and/or function of cilia. Most patients currently recognised to have PCD have ultrastructural defects of cilia; however, some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11).
Objectives To test further for mutant DNAH11 as a cause of PCD, DNAH11 was sequenced in patients with a PCD clinical phenotype, but no known genetic aetiology.
Methods 82 exons and intron/exon junctions in DNAH11 were sequenced in 163 unrelated patients with a clinical phenotype of PCD, including those with normal ciliary ultrastructure (n=58), defects in outer and/or inner dynein arms (n=76), radial spoke/central pair defects (n=6), and 23 without definitive ultrastructural results, but who had situs inversus (n=17), or bronchiectasis and/or low nasal nitric oxide (n=6). Additionally, DNAH11 was sequenced in 13 subjects with isolated situs abnormalities to see if mutant DNAH11 could cause situs defects without respiratory disease.
Results Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11; and two patients without ultrastructural analysis had biallelic mutations. All mutations were novel and private. None of the patients with dynein arm or radial spoke/central pair defects, or isolated situs abnormalities, had mutations in DNAH11. Of the 35 identified mutant alleles, 24 (69%) were nonsense, insertion/deletion or loss-of-function splice-site mutations.
Conclusions Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients.
C1 [Knowles, Michael R.; Burns, Kimberlie A.; Minnix, Susan L.; Armstrong, Michael C.; Lori, Adriana; Hazucha, Milan J.] UNC Sch Med, Dept Med, Chapel Hill, NC USA.
[Leigh, Margaret W.; Carson, Johnny L.; Davis, Stephanie D.] UNC Sch Med, Dept Pediat, Chapel Hill, NC USA.
[Dell, Sharon D.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada.
[Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Sagel, Scott D.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
[Rosenfeld, Margaret] Childrens Hosp & Reg Med Ctr, Seattle, WA USA.
[Loges, Niki T.; Becker-Heck, Anita; Schmidts, Miriam; Omran, Heymut] Univ Hosp, Dept Pediat & Adolescent Med, Freiburg, Germany.
[Loges, Niki T.; Olbrich, Heike; Becker-Heck, Anita; Werner, Claudius; Omran, Heymut] Univ Klinikum Munster, Klin & Poliklin Kinder & Jugendmed Allgemeine Pad, Munster, Germany.
[Loges, Niki T.; Becker-Heck, Anita] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany.
[Zariwala, Maimoona A.] UNC Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA.
RP Knowles, MR (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Sch Med, CB 7248,7123 Thurston Bowles Bldg, Chapel Hill, NC 27599 USA.
EM knowles@med.unc.edu
RI Schmidts, Miriam/A-3777-2012;
OI Schmidts, Miriam/0000-0002-1714-6749; Milla, Carlos/0000-0001-5515-3053
FU National Institute of Health [5 U54 HL096458-06]; Office of the
Director; ORDR; NHLBI; National Institutes of Health [5 R01HL071798];
Children's Discovery Institute; National Institute of Allergy and
Infectious Diseases; Flight Attendant Medical Research Institute;
Deutsche Forschungsgemeinschaft (DFG) [Om 6/4, GRK1104, SFB592]; US
Federal government from National Heart, Lung, and Blood Institute
[N01-HV-48194]; National Center of Research Resources [RR00046, UL1
RR025747, UL1 RR025780]; NHLBI [5 U54 HL096458-06, P01 HL034322]; CFF
[R026-CR07]; NIH Office of Rare Diseases Research (ORDR); [R01 HL08265]
FX MRK, MWL, JLC, MJH, SLM, SDD, TWF, KNO, SDS, MR, KEB, MCA, AL and MAZ
are supported by National Institute of Health research grant 5 U54
HL096458-06, funded by the Office of the Director, and supported by ORDR
and NHLBI, NIH. MRK and MAZ are supported by National Institutes of
Health grant 5 R01HL071798. TWF is supported by R01 HL08265 and
Children's Discovery Institute. KNO is supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases. JLC is supported by Clinical Innovator Award by Flight
Attendant Medical Research Institute. HO is supported by a grant from
the Deutsche Forschungsgemeinschaft (DFG Om 6/4, GRK1104, SFB592).
Resequencing was provided by the University of Washington, Department of
Genome Sciences, under US Federal government contract number
N01-HV-48194 from National Heart, Lung, and Blood Institute. This work
was supported in part by grants RR00046, UL1 RR025747 and UL1 RR025780
from the National Center of Research Resources, NHLBI P01 HL034322, NIH
and CFF R026-CR07. This consortium, Genetic Disorders of Mucociliary
Clearance is part of NIH Rare Diseases Clinical Research Network
(RDCRN). Funding and/or programmatic support for this project was
provided by grant 5 U54 HL096458-06 from the NHLBI and the NIH Office of
Rare Diseases Research (ORDR). The views expressed do not necessarily
reflect the official policies of the Department of Health and Human
Services; nor does mention by trade names, commercial practices, or
organisations imply endorsement by the U.S government.
NR 42
TC 51
Z9 54
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
EI 1468-3296
J9 THORAX
JI Thorax
PD MAY
PY 2012
VL 67
IS 5
BP 433
EP 441
DI 10.1136/thoraxjnl-2011-200301
PG 9
WC Respiratory System
SC Respiratory System
GA 928CX
UT WOS:000302959000014
PM 22184204
ER
PT J
AU Consonni, D
De Matteis, S
Pesatori, AC
Cattaneo, A
Cavallo, DM
Lubin, JH
Tucker, M
Bertazzi, PA
Caporaso, NE
Wacholder, S
Landi, MT
AF Consonni, Dario
De Matteis, Sara
Pesatori, Angela C.
Cattaneo, Andrea
Cavallo, Domenico M.
Lubin, Jay H.
Tucker, Margaret
Bertazzi, Pier Alberto
Caporaso, Neil E.
Wacholder, Sholom
Landi, Maria Teresa
TI Increased lung cancer risk among bricklayers in an Italian
population-based case-control study
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE epidemiology; occupational health; case-control study; pulmonary
neoplasms; construction industry
ID CONSTRUCTION-INDUSTRY; OCCUPATIONAL EXPOSURES; MORTALITY; SILICA;
HEALTH; WORK; CARCINOGENS; PREVENTION; COMMUNITY; UK
AB Background Bricklayers may be at increased risk of lung cancer, although a firm association has not been established. We examined this association within the EAGLE (Environment And Genetics in Lung cancer Etiology) study, a population-based casecontrol study conducted in Italy between 2002 and 2005.
Methods For men in selected occupations in the construction sector we calculated smoking-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). For bricklayers we estimated the population attributable fraction (PAF) and the attributable community risk (ACR).
Results We found increased lung cancer risk for bricklayers (OR 1.57, 95% CI 1.12-2.21; 147 cases, 81 controls). The PAF was 3.9% (95% CI 0.7-7.0), corresponding to an ACR of 4.1 cases annually per 100,000 men (95% CI 0.7-7.3) in the whole community. Among bricklayers, there were increased risks for squamous cell (OR 2.03, 95% CI 1.32-3.13, 56 exposed cases) and small cell carcinomas (OR 2.29, 95% CI 1.29-4.07, 21 exposed cases), while no excess (OR 1.06, 95% CI 0.68-1.65, 41 exposed cases) was found for adenocarcinoma.
Conclusions Our findings provide additional evidence of increased lung cancer risk in Italian bricklayers. The association is plausible because they are exposed to several carcinogens, notably crystalline silica. Am. J. Ind. Med. 55: 423-428, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Consonni, Dario; De Matteis, Sara; Pesatori, Angela C.; Bertazzi, Pier Alberto] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dept Prevent Med, Epidemiol Unit, I-20122 Milan, Italy.
[De Matteis, Sara; Pesatori, Angela C.; Cavallo, Domenico M.; Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy.
[Cattaneo, Andrea; Cavallo, Domenico M.] Univ Insubria, Dept Chem & Environm Sci, Como, Italy.
[De Matteis, Sara; Lubin, Jay H.; Tucker, Margaret; Caporaso, Neil E.; Wacholder, Sholom; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Consonni, D (reprint author), Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dept Prevent Med, Epidemiol Unit, Via San Barnaba, I-20122 Milan, Italy.
EM dario.consonni@unimi.it
RI Cavallo, Domenico Maria/F-9881-2013; Tucker, Margaret/B-4297-2015;
Cattaneo, Andrea/J-4791-2013; Consonni, Dario/K-7943-2016; bertazzi,
pietro alberto/D-5039-2017;
OI Cavallo, Domenico Maria/0000-0003-1853-2999; Cattaneo,
Andrea/0000-0002-2962-7259; Consonni, Dario/0000-0002-8935-3843;
bertazzi, pietro alberto/0000-0003-3475-2449; pesatori,
angela/0000-0002-0261-3252
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics, Bethesda, MD, USA; Lombardy Region
(Environmental Epidemiology Program), Milan, Italy; CARIPLO Foundation,
Milan, Italy; Istituto Nazionale per l'Assicurazione contro gli
Infortuni sul Lavoro, INAIL, Rome, Italy
FX The authors wish to thank Dr. Ester Bramati for helping to code
occupational histories. They also express their gratitude to all the
EAGLE study participants and collaborators (listed on the EAGLE website
at http://eagle.cancer.gov/), whose contribution made this study
possible. This work was supported by: Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics, Bethesda, MD, USA; Lombardy Region
(Environmental Epidemiology Program), Milan, Italy; CARIPLO Foundation,
Milan, Italy; Istituto Nazionale per l'Assicurazione contro gli
Infortuni sul Lavoro, INAIL, Rome, Italy.
NR 30
TC 4
Z9 4
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD MAY
PY 2012
VL 55
IS 5
BP 423
EP 428
DI 10.1002/ajim.22017
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 925XD
UT WOS:000302794500003
PM 22298231
ER
PT J
AU Epstein, DH
Preston, KL
AF Epstein, David H.
Preston, Kenzie L.
TI TGI Monday?: Drug-Dependent Outpatients Report Lower Stress and More
Happiness at Work than Elsewhere
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID DAILY-LIFE; NEGATIVE AFFECT; FOLLOW-UP; COCAINE; MOOD; SMOKING;
CONTRASTS; RESPONSES; PATTERNS; EXERCISE
AB In the general population, experience-sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25-week natural-history study, 79 employed methadone-maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance-disorder patients (for whom work may be a respite from drug-using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors). (Am J Addict 2012;21:189198)
C1 [Epstein, David H.; Preston, Kenzie L.] NIDA, Treatment Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Epstein, DH (reprint author), NIDA, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch, Room 01B-606,251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM depstein@intra.nida.nih.gov
RI Preston, Kenzie/J-5830-2013
OI Preston, Kenzie/0000-0003-0603-2479
FU Intramural NIH HHS [Z99 DA999999]
NR 34
TC 6
Z9 6
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
EI 1521-0391
J9 AM J ADDICTION
JI Am. J. Addict.
PD MAY-JUN
PY 2012
VL 21
IS 3
BP 189
EP 198
DI 10.1111/j.1521-0391.2012.00230.x
PG 10
WC Substance Abuse
SC Substance Abuse
GA 923IL
UT WOS:000302612900003
PM 22494220
ER
PT J
AU Stewart, PA
Vermeulen, R
Coble, JB
Blair, A
Schleiff, P
Lubin, JH
Attfield, M
Silverman, DT
AF Stewart, Patricia A.
Vermeulen, Roel
Coble, Joseph B.
Blair, Aaron
Schleiff, Patricia
Lubin, Jay H.
Attfield, Mike
Silverman, Debra T.
TI The Diesel Exhaust in Miners Study: V. Evaluation of the Exposure
Assessment Methods
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE diesel exhaust; elemental carbon; exposure assessment; mining
ID NONMETAL MINING FACILITIES; PARTICULATE MATTER; ELEMENTAL CARBON
AB Exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), was assessed for an epidemiologic study investigating the association between DE and mortality, particularly from lung cancer, among miners at eight mining facilities from the date of dieselization (1947-1967) through 1997. To provide insight into the quality of the estimates for use in the epidemiologic analyses, several approaches were taken to evaluate the exposure assessment process and the quality of the estimates. An analysis of variance was conducted to evaluate the variability of 1998-2001 REC measurements within and between exposure groups of underground jobs. Estimates for the surface exposure groups were evaluated to determine if the arithmetic means (AMs) of the REC measurements increased with increased proximity to, or use of, diesel-powered equipment, which was the basis on which the surface groups were formed. Estimates of carbon monoxide (CO) (another component of DE) air concentrations in 1976-1977, derived from models developed to predict estimated historical exposures, were compared to 1976-1977 CO measurement data that had not been used in the model development. Alternative sets of estimates were developed to investigate the robustness of various model assumptions. These estimates were based on prediction models using: (i) REC medians rather AMs, (ii) a different CO:REC proportionality than a 1:1 relation, and (iii) 5-year averages of historical CO measurements rather than modeled historical CO measurements and DE-related determinants. The analysis of variance found that in three of the facilities, most of the between-group variability in the underground measurements was explained by the use of job titles. There was relatively little between-group variability in the other facilities. The estimated REC AMs for the surface exposure groups rose overall from 1 to 5 mu g m(-3) as proximity to, and use of, diesel equipment increased. The alternative estimates overall were highly correlated (similar to 0.9) with the primary set of estimates. The median of the relative differences between the 1976-1977 CO measurement means and the 1976-1977 estimates for six facilities was 29%. Comparison of estimated CO air concentrations from the facility-specific prediction models with historical CO measurement data found an overall agreement similar to that observed in other epidemiologic studies. Other evaluations of components of the exposure assessment process found moderate to excellent agreement. Thus, the overall evidence suggests that the estimates were likely accurate representations of historical personal exposure levels to DE and are useful for epidemiologic analyses.
C1 [Stewart, Patricia A.; Vermeulen, Roel; Coble, Joseph B.; Blair, Aaron; Lubin, Jay H.; Silverman, Debra T.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Schleiff, Patricia; Attfield, Mike] US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA.
RP Silverman, DT (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM silvermd@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute
FX Division of Cancer Epidemiology and Genetics of the National Cancer
Institute.
NR 15
TC 13
Z9 13
U1 1
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD MAY
PY 2012
VL 56
IS 4
BP 389
EP 400
DI 10.1093/annhyg/mes020
PG 12
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA 926BP
UT WOS:000302806600003
ER
PT J
AU Nichols, JH
Loeb, S
Metter, EJ
Ferrucci, L
Carter, HB
AF Nichols, John H.
Loeb, Stacy
Metter, E. Jeffrey
Ferrucci, Luigi
Carter, H. Ballentine
TI The relationship between prostate volume and prostate-specific antigen
variability: data from the Baltimore Longitudinal Study of Aging and the
Johns Hopkins Active Surveillance Program
SO BJU INTERNATIONAL
LA English
DT Article
DE PSA; prostate volume; PSA variability
ID CANCER; SERUM; MORTALITY; VELOCITY; MEN; MRI
AB OBJECTIVE
To clarify the relationship between serial prostate-specific antigen (PSA) variability and prostate volume in both cancer-free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low-risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS).
MATERIALS AND METHODS
In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements.
PSA variability was calculated in ng/mL per year, and a linear mixed-effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time.
RESULTS
In a model with prostate volume, age and baseline PSA, there was no significant relationship between prostate volume and PSA variability (BLSA, P = 0.57; AS, P = 0.49).
Only baseline PSA showed a significant relationship to PSA yearly variability (PSAYV) (P < 0.001). Specifically, a one unit higher baseline PSA (ng/mL) corresponded on average to 0.09 and 0.06 ng/mL per year higher PSAYV in the BLSA and AS populations, respectively.
CONCLUSIONS
The results of the present study suggest that the primary driver of PSA variability is the baseline PSA level, rather than prostate volume.
Clinicians might consider the baseline PSA level to help predict the expected variability in serial PSA measurements.
C1 [Nichols, John H.] Johns Hopkins Univ Hosp, Sch Med, Baltimore, MD 21287 USA.
[Loeb, Stacy; Carter, H. Ballentine] Johns Hopkins Univ Hosp, Dept Urol, Baltimore, MD 21287 USA.
[Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Nichols, JH (reprint author), Johns Hopkins Univ Hosp, Sch Med, Urol Marburg 145,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jnicho22@jhmi.edu
OI Loeb, Stacy/0000-0003-3933-9207
FU National Institutes of Health, the National Institute on Aging; James
Buchanan Brady Urological Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, the National Institute on Aging,
and the James Buchanan Brady Urological Institute.
NR 15
TC 2
Z9 2
U1 0
U2 2
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 MAY
PY 2012
VL 109
IS 9
BP 1304
EP 1308
DI 10.1111/j.1464-410X.2011.10663.x
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 923JR
UT WOS:000302616100009
PM 22093443
ER
PT J
AU Oz, M
Isaev, D
Lorke, DE
Hasan, M
Petroianu, G
Shippenberg, TS
AF Oz, Murat
Isaev, Dmytro
Lorke, Dietrich E.
Hasan, Muhammed
Petroianu, Georg
Shippenberg, Toni S.
TI Methylene blue inhibits function of the 5-HT transporter
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE 5-HT transporter; methylene blue; HEK-293 cells
ID SPATIALLY-RESOLVED ANALYSIS; SEROTONIN TOXICITY; NITRIC-OXIDE;
FLUORESCENT SUBSTRATE; REAL-TIME; RECEPTORS; MICE; PARATHYROIDECTOMY;
ENCEPHALOPATHY; LOCALIZATION
AB BACKGROUND AND PURPOSE Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB on SERT. EXPERIMENTAL APPROACH Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP+), [ 3H] 5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. KEY RESULTS In EM4 cells expressing GFP-tagged human SERT (hSERT), MB concentration-dependently inhibited ASP+ accumulation (IC50: 1.4 +/- 0.3 mM). A similar effect was observed in N2A cells. Uptake of [ 3H] 5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT-evoked ion currents. Pretreatment with 8-Br-cGMP did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca2+ levels remained unchanged during MB application. Further experiments revealed that ASP+ binding to cell surface hSERT was reduced after MB treatment. In whole-cell radioligand experiments, exposure to MB (10 mM; 10 min) did not alter surface binding of the SERT ligand [ 125I] RTI-55. CONCLUSIONS AND IMPLICATIONS MB modulated SERT function and suggested that SERT may be an additional target upon which MB acts to produce 5-HT toxicity.
C1 [Oz, Murat; Isaev, Dmytro; Hasan, Muhammed] UAE Univ, Fac Med & Hlth Sci, Dept Pharmacol, Funct Lipid Branch, Al Ain, U Arab Emirates.
[Lorke, Dietrich E.] UAE Univ, Fac Med & Hlth Sci, Dept Anat, Al Ain, U Arab Emirates.
[Lorke, Dietrich E.; Petroianu, Georg] Florida Int Univ, Coll Med, Dept Cellular Biol & Pharmacol, Miami, FL 33199 USA.
[Shippenberg, Toni S.] Natl Inst Drug Abuse, Integrat Neurosci Sect, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Baltimore, MD USA.
RP Oz, M (reprint author), United Arab Emirates Univ, Dept Pharmacol, Funct Lipid Branch, Fac Med & Hlth Sci, Abu Dhabi, U Arab Emirates.
EM Murat_Oz@uaeu.ac.ae
RI Oz, Murat/E-2148-2012
FU NIH/NIDA; UAE University
FX This research was supported by the NIH/NIDA Intramural Research Program
and grants from the individual grants from UAE University. Authors would
like to thank Dr Harald Sitte of Medical University of Vienna for kindly
supplying hSERT cDNA.
NR 43
TC 7
Z9 8
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD MAY
PY 2012
VL 166
IS 1
SI SI
BP 168
EP 176
DI 10.1111/j.1476-5381.2011.01462.x
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 923FZ
UT WOS:000302606200015
PM 21542830
ER
PT J
AU Winkler, EAH
Gardiner, PA
Clark, BK
Matthews, CE
Owen, N
Healy, GN
AF Winkler, Elisabeth A. H.
Gardiner, Paul A.
Clark, Bronwyn K.
Matthews, Charles E.
Owen, Neville
Healy, Genevieve N.
TI Identifying sedentary time using automated estimates of accelerometer
wear time
SO BRITISH JOURNAL OF SPORTS MEDICINE
LA English
DT Article
ID PHYSICAL-ACTIVITY; UNITED-STATES; CALIBRATION; ADULTS; OUTPUT
AB Purpose The authors evaluated the accuracy of three automated accelerometer wear-time estimation algorithms against self-report. Direct effects on sedentary time (<100 cpm) and indirect effects on moderate-to-vigorous physical activity (MVPA, >= 1952 cpm) time were examined.
Methods A subsample from the 2004/2005 Australian Diabetes, Obesity and Lifestyle Study (n=148) completed activity logs and wore accelerometers for a total of 987 days. A published algorithm that allows movement within non-wear periods (Algorithm 1) was compared with one that allows less movement (Algorithm 2) or no movement (Algorithm 3). Implications for population estimates were examined using 2003/2004 US National Health and Nutrition Examination Survey data.
Results Mean difference per day between the criterion and estimated wear time was negligible for all three algorithms (<= 11 min), but 95% limits of agreement (LOA) were wide (+/->= 2 h). Respectively, the algorithms (1, 2 and 3) misclassified sedentary time as non-wear on 31.9%, 19.4% and 18% of days and misclassified non-wear time as sedentary on 42.8%, 43.7% and 51.3% of days. Use of Algorithm 2 (compared with Algorithm 1) affected population estimates of sedentary time (higher by 20 min/day) but not MVPA time. Agreement between Algorithms 1 and 2 was good for MVPA time (mean difference -0.08, LOA: -2.08, 1.91 min), but not for wear time or sedentary time.
Conclusion Accelerometer wear time can be estimated accurately on average; however, misclassification can be substantial for individuals. Algorithm choice affects estimates of sedentary time. Allowing very limited movement within non-wear periods can improve accuracy.
C1 [Winkler, Elisabeth A. H.; Gardiner, Paul A.; Clark, Bronwyn K.; Owen, Neville; Healy, Genevieve N.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Owen, Neville; Healy, Genevieve N.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
RP Winkler, EAH (reprint author), Univ Queensland, Canc Prevent Res Ctr, Sch Populat Hlth, Herston Rd, Herston, Qld 4006, Australia.
EM e.winkler@uq.edu.au
RI Clark, Bronwyn/F-8028-2010; Healy, Genevieve/A-7408-2008; Gardiner,
Paul/F-2751-2010; Owen, Neville/K-5986-2012; matthews,
Charles/E-8073-2015
OI Clark, Bronwyn/0000-0001-7527-4311; Owen, Neville/0000-0003-2784-4820;
Healy, Genevieve/0000-0001-7093-7892; Gardiner,
Paul/0000-0002-8072-2673; matthews, Charles/0000-0001-8037-3103
FU Queensland Health Core Research Infrastructure grant; NHMRC [569940,
569861]; Heart Foundation of Australia [PP 06B 2889]; Australian
Post-graduate Award; NHMRC/National Heart Foundation of Australia [PH
374 08B 3905]
FX BKC, PAG, GNH, EAHW and NO are supported by a Queensland Health Core
Research Infrastructure grant and by NHMRC Program Grant funding
(#569940). PAG is supported by a Heart Foundation of Australia (# PP 06B
2889). BKC is supported by an Australian Post-graduate Award. GNH is
also supported by a NHMRC (#569861)/National Heart Foundation of
Australia (PH 374 08B 3905) Postdoctoral Fellowship.
NR 20
TC 39
Z9 39
U1 2
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-3674
J9 BRIT J SPORT MED
JI Br. J. Sports Med.
PD MAY
PY 2012
VL 46
IS 6
BP 436
EP 442
DI 10.1136/bjsm.2010.079699
PG 7
WC Sport Sciences
SC Sport Sciences
GA 925CC
UT WOS:000302737100013
PM 21504965
ER
PT J
AU Riggs, ER
Church, DM
Hanson, K
Horner, VL
Kaminsky, EB
Kuhn, RM
Wain, KE
Williams, ES
Aradhya, S
Kearney, HM
Ledbetter, DH
South, ST
Thorland, EC
Martin, CL
AF Riggs, E. R.
Church, D. M.
Hanson, K.
Horner, V. L.
Kaminsky, E. B.
Kuhn, R. M.
Wain, K. E.
Williams, E. S.
Aradhya, S.
Kearney, H. M.
Ledbetter, D. H.
South, S. T.
Thorland, E. C.
Martin, C. L.
TI Towards an evidence-based process for the clinical interpretation of
copy number variation
SO CLINICAL GENETICS
LA English
DT Article
DE Cytogenetics; DNA copy number variation; evidence-based practice; gene
dosage; oligonucleotide array sequence analysis
ID EVIDENCE-BASED MEDICINE; MOWAT-WILSON-SYNDROME; EGAPP WORKING GROUP; RET
PROTOONCOGENE; HUMAN GENOME; HIRSCHSPRUNG DISEASE;
DEVELOPMENTAL-DISABILITIES; HEREDITARY NEUROPATHY; STRUCTURAL VARIATION;
PRESSURE PALSIES
AB The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.
C1 [Riggs, E. R.; Horner, V. L.; Kaminsky, E. B.; Williams, E. S.; Martin, C. L.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
[Church, D. M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Hanson, K.] Sequenom Inc, San Diego, CA USA.
[Kuhn, R. M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Wain, K. E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Aradhya, S.] GeneDx, Gaithersburg, MD USA.
[Kearney, H. M.; Thorland, E. C.] Mission Hlth Syst, Fullerton Genet Ctr, Asheville, NC USA.
[Ledbetter, D. H.] Geisinger Hlth Syst, Danville, PA USA.
[South, S. T.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[South, S. T.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[South, S. T.] ARUP Labs, Salt Lake City, UT USA.
RP Martin, CL (reprint author), Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Suite 301, Atlanta, GA 30322 USA.
EM christa.martin@emory.edu
FU NIH [HD064525]; NIH, National Library of Medicine
FX This work was supported, in part, by NIH Grant HD064525 ( D. H. L. and
C. L. M.) and by the Intramural Research Program of the NIH, National
Library of Medicine.
NR 53
TC 34
Z9 36
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD MAY
PY 2012
VL 81
IS 5
BP 403
EP 412
DI 10.1111/j.1399-0004.2011.01818.x
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 923KH
UT WOS:000302617700001
PM 22097934
ER
PT J
AU Ali, RA
Rehman, AU
Khan, SN
Husnain, T
Riazuddin, S
Friedman, TB
Ahmed, ZM
Riazuddin, S
AF Ali, R. A.
Rehman, A. U.
Khan, S. N.
Husnain, T.
Riazuddin, S.
Friedman, T. B.
Ahmed, Z. M.
Riazuddin, S.
TI DFNB86, a novel autosomal recessive non-syndromic deafness locus on
chromosome 16p13.3
SO CLINICAL GENETICS
LA English
DT Letter
ID MUTATIONS; MICE
C1 [Riazuddin, S.] Cincinnati Childrens Hosp, Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Mol Genet Lab,Childrens Hosp Res Fdn, Cincinnati, OH USA.
[Ali, R. A.; Khan, S. N.; Husnain, T.; Ahmed, Z. M.; Riazuddin, S.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Rehman, A. U.; Friedman, T. B.] NIDOCD, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD USA.
[Khan, S. N.; Riazuddin, S.] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Ahmed, Z. M.; Riazuddin, S.] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH 45221 USA.
[Ahmed, Z. M.; Riazuddin, S.] Univ Cincinnati, Cincinnati Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH 45221 USA.
[Ahmed, Z. M.; Riazuddin, S.] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH 45221 USA.
RP Riazuddin, S (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Mol Genet Lab,Childrens Hosp Res Fdn, Cincinnati, OH USA.
EM saima.riazuddin@cchmc.org; saima.riazuddin@cchmc.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015
FU Cincinnati Children's Hospital Research Foundation; National Institute
on Deafness and Other Communication Disorders (NIDCD/NIH)
[R00-DC009287-03]; RPB; Higher Education Commission, Islamabad;
EMRO/WHO-COMSTECH; Ministry of Science and Technology, Islamabad;
International Center for Genetic Engineering and Biotechnology, Trieste,
Italy [CRP/PAK08-01, 08/009]; NIDCD/NIH [DC00039-14]
FX The authors are grateful to the family for contributing to this study.
We thank Alejandro Schaffer for suggestions regarding statistical
analysis of our linkage data. We also thank Dennis Drayna and Changsoo
Kang for their critiques. This study was supported by the Cincinnati
Children's Hospital Research Foundation intramural research funds to Si.
R. and Z. M. A., the National Institute on Deafness and Other
Communication Disorders (NIDCD/NIH) research grant R00-DC009287-03 to Z.
A. Z. A. is also a recipient of RPB Career Development Award. Work in
Pakistan was supported by the Higher Education Commission, Islamabad,
EMRO/WHO-COMSTECH, Ministry of Science and Technology, Islamabad and the
International Center for Genetic Engineering and Biotechnology, Trieste,
Italy, under project CRP/PAK08-01 Contract no. 08/009 to Sh. R. This
study was also supported by intramural funds from the NIDCD/NIH
DC00039-14 to T. B. F.
NR 9
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD MAY
PY 2012
VL 81
IS 5
BP 498
EP 500
DI 10.1111/j.1399-0004.2011.01729.x
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 923KH
UT WOS:000302617700016
PM 22211675
ER
PT J
AU Nelson, EL
Konidaris, GD
Berthier, NE
Braun, MC
Novak, MFSX
Suomi, SJ
Novak, MA
AF Nelson, Eliza L.
Konidaris, George D.
Berthier, Neil E.
Braun, Maurine C.
Novak, Matthew F. S. X.
Suomi, Stephen J.
Novak, Melinda A.
TI Kinematics of reaching and implications for handedness in rhesus monkey
infants
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE handedness; reaching; kinematics; primate; infant
ID MACAQUES MACACA-MULATTA; CAPUCHINS CEBUS-APELLA; HAND PREFERENCES;
PREHENSION MOVEMENTS; NONHUMAN-PRIMATES; OBJECT SIZE; LOCATION; TASK
AB Kinematic studies of reaching in human infants using two-dimensional (2-D) and three-dimensional (3-D) recordings have complemented behavioral studies of infant handedness by providing additional evidence of early right asymmetries. Right hand reaches have been reported to be straighter and smoother than left hand reaches during the first year. Although reaching has been a popular measure of handedness in primates, there has been no systematic comparison of left and right hand reach kinematics. We investigated reaching in infant rhesus monkeys using the 2-D motion analysis software MaxTRAQ Lite+ (Innovision Systems). Linear mixed-effects models revealed that left hand reaches were smoother, but not straighter, than right hand reaches. An early left bias matches previous findings of a left hand preference for reaching in adult rhesus monkeys. Additional work using this kind of kinematic approach will extend our understanding of primate handedness beyond traditional studies measuring only frequency or bouts of hand use. (c) 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:460467, 2012.
C1 [Konidaris, George D.] Univ Massachusetts, Dept Comp Sci, Amherst, MA 01003 USA.
[Novak, Matthew F. S. X.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Dept Hlth & Human Serv, NIH, Poolesville, MD USA.
[Nelson, Eliza L.; Berthier, Neil E.; Braun, Maurine C.; Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
RP Nelson, EL (reprint author), Univ N Carolina Chapel Hill, Ctr Dev Sci, 100 E Franklin St,Suite 200,CB 8115, Chapel Hill, NC 27599 USA.
EM eliza_nelson@unc.edu
OI Nelson, Eliza/0000-0003-0058-8409
FU Division of Intramural Research, NICHD
FX Contract grant sponsor: Division of Intramural Research, NICHD.
NR 44
TC 1
Z9 1
U1 2
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0012-1630
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD MAY
PY 2012
VL 54
IS 4
BP 460
EP 467
DI 10.1002/dev.20604
PG 8
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA 919VM
UT WOS:000302358800010
PM 22031459
ER
PT J
AU Stang, A
Trabert, B
Wentzensen, N
Cook, MB
Rusner, C
Oosterhuis, JW
McGlynn, KA
AF Stang, A.
Trabert, B.
Wentzensen, N.
Cook, M. B.
Rusner, C.
Oosterhuis, J. W.
McGlynn, K. A.
TI Burden of extragonadal germ cell tumours in Europe and the United States
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Letter
C1 [Stang, A.; Rusner, C.] Univ Halle Wittenberg, Inst Clin Epidemiol, Fac Med, D-06097 Halle, Saale, Germany.
[Trabert, B.; Wentzensen, N.; Cook, M. B.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Oosterhuis, J. W.] Erasmus MC, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands.
RP Stang, A (reprint author), Univ Halle Wittenberg, Inst Clin Epidemiol, Fac Med, Magdeburger Str 8, D-06097 Halle, Saale, Germany.
EM andreas.stang@medizin.uni-halle.de
RI Cook, Michael/A-5641-2009; Trabert, Britton/F-8051-2015
OI Cook, Michael/0000-0002-0533-7302;
FU Intramural NIH HHS [Z01 CP010126-13]
NR 4
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2012
VL 48
IS 7
BP 1116
EP 1117
DI 10.1016/j.ejca.2012.02.061
PG 2
WC Oncology
SC Oncology
GA 925RU
UT WOS:000302779700020
PM 22425262
ER
PT J
AU Goedert, JJ
Pfeiffer, R
Zhu, MZ
Yang, XHR
Garcia-Closas, M
Lissowska, J
Kopp, WC
AF Goedert, James J.
Pfeiffer, Ruth
Zhu, Mingzhu
Yang, Xiaohong R.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Kopp, William C.
TI Peripheral blood immunologic phenotype of population-based breast cancer
cases and matched controls
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Letter
ID REGULATORY T-CELLS; RISK; CD4
C1 [Goedert, James J.; Pfeiffer, Ruth; Yang, Xiaohong R.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Zhu, Mingzhu; Kopp, William C.] SAIC Frederick Inc, Clin Support Lab, Frederick, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] Ctr Canc, Warsaw, Poland.
RP Goedert, JJ (reprint author), 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Lissowska,
Jolanta/0000-0003-2695-5799
FU Intramural NIH HHS [ZIA CP010214-01]
NR 10
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD MAY
PY 2012
VL 42
IS 5
BP 572
EP 574
DI 10.1111/j.1365-2362.2011.02610.x
PG 3
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 923KT
UT WOS:000302618900015
PM 22073930
ER
PT J
AU Prabakaran, P
Chen, WZ
Singarayan, MG
Stewart, CC
Streaker, E
Feng, Y
Dimitrov, DS
AF Prabakaran, Ponraj
Chen, Weizao
Singarayan, Maria G.
Stewart, Claudia C.
Streaker, Emily
Feng, Yang
Dimitrov, Dimiter S.
TI Expressed antibody repertoires in human cord blood cells: 454 sequencing
and IMGT/HighV-QUEST analysis of germline gene usage, junctional
diversity, and somatic mutations
SO IMMUNOGENETICS
LA English
DT Article
DE 454 Sequencing; IMGT/HighV-QUEST; Antibodyome; Human cord blood;
Antibody repertoire; IgM; Immunoglobulin; Antibody library
ID VARIABLE-REGION GENES; IMMUNOGLOBULIN REPERTOIRE; B-CELLS; IGM
ANTIBODIES; V-H; CHAIN; CDR-H3; LIBRARY; IDENTIFICATION; CONSTRUCTION
AB Human cord blood cell-derived IgM antibodies are important for the neonate immune responses and construction of germline-based immunoglobulin libraries. Several previous studies of a relatively small number of sequences found that they exhibit restrictions in the usage of germline genes and in the diversity of the variable heavy chain complementarity determining region 3 compared to adults. To further characterize such restrictions on a larger scale and to compare the early B-cell diversity to adult IgM repertoires, we performed 454 sequencing and IMGT/HighV-QUEST analysis of cord blood IG libraries from two babies and determined germline gene usage, V-D-J rearrangement, VHCDR3 diversity, and somatic mutations to characterize human neonate repertoire. Most of the germline subgroups were identified with frequencies comparable to those present in the adult IgM repertoire except for the IGHV1-2 gene that was preferentially expressed in the cord blood cells. The gene usage diversity contributed to 1,430 unique IGH V-D-J rearrangement patterns while the exonuclease trimming and N region addition at the V-D-J junctions along with gene diversity created a wide range of VHCDR3 with different lengths and sequence variability. We observed a lower degree of somatic mutations in the CDR and framework regions of antibodies from cord blood cells compared to adults. These results provide insights into the characteristics of human cord blood antibody repertoires, which have gene usage diversity and VHCDR3 lengths similar to that of the adult IgM repertoire but differ significantly in some of the gene usages, V-D-J rearrangements, junctional diversity, and somatic mutations.
C1 [Prabakaran, Ponraj; Chen, Weizao; Streaker, Emily; Feng, Yang; Dimitrov, Dimiter S.] Natl Canc Inst NCI Frederick, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA.
[Prabakaran, Ponraj; Streaker, Emily] NCI Frederick, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Stewart, Claudia C.] NCI Frederick, Lab Mol Technol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), Natl Canc Inst NCI Frederick, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM dimiter.dimitrov@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NIH,
National Cancer Institute [NO1-CO-12400]
FX We thank the Laboratory of Molecular Technology of SAIC-Frederick Inc.
for providing Roche 454 sequencing service. We are grateful to Eltaf
Alamyar and to the IMGT (R) team for providing access to
IMGT/HighV-QUEST. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, and by Federal funds from the NIH, National Cancer Institute,
under contract no. NO1-CO-12400. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does the mention of trade names,
commercial products, or organizations imply endorsement by the US
Government.
NR 61
TC 21
Z9 23
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
J9 IMMUNOGENETICS
JI Immunogenetics
PD MAY
PY 2012
VL 64
IS 5
BP 337
EP 350
DI 10.1007/s00251-011-0595-8
PG 14
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 925HC
UT WOS:000302750800001
PM 22200891
ER
PT J
AU Ayele, FT
Doumatey, A
Huang, HX
Zhou, J
Charles, B
Erdos, M
Adeleye, J
Balogun, W
Fasanmade, O
Johnson, T
Oli, J
Okafor, G
Amoah, A
Eghan, BA
Agyenim-Boateng, K
Acheampong, J
Adebamowo, CA
Herbert, A
Gerry, N
Christman, M
Chen, GJ
Shriner, D
Adeyemo, A
Rotimi, CN
AF Ayele, Fasil Tekola
Doumatey, Ayo
Huang, Hanxia
Zhou, Jie
Charles, Bashira
Erdos, Michael
Adeleye, Jokotade
Balogun, Williams
Fasanmade, Olufemi
Johnson, Thomas
Oli, Johnnie
Okafor, Godfrey
Amoah, Albert
Eghan, Benjamin A., Jr.
Agyenim-Boateng, Kofi
Acheampong, Joseph
Adebamowo, Clement A.
Herbert, Alan
Gerry, Norman
Christman, Michael
Chen, Guanjie
Shriner, Daniel
Adeyemo, Adebowale
Rotimi, Charles N.
TI Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and
IL-6 levels in African Americans
SO IMMUNOGENETICS
LA English
DT Article
DE Interleukin; Interleukin-10; Interleukin-1Ra; Interleukin-6; Genome-wide
association study; African American
ID C-REACTIVE PROTEIN; RECEPTOR ANTAGONIST GENE; PLASMA-LEVELS; PROMOTER
POLYMORPHISMS; INSULIN-RESISTANCE; CIRCULATING LEVELS;
DIABETES-MELLITUS; ADIPOSE-TISSUE; BLOOD-PRESSURE; WEST AFRICANS
AB Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p < 5 x 10(-8)) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p = 2.30 x 10(-10)). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p = 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p = 2.55 x 10(-7)), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 x 10(-6) to 1.75 x 10(-6)), and 23 SNPs near the IL1A gene (p = 1.22 x 10(-6) to 1.63 x 10(-6)). We also successfully replicated rs4251961 (p = 0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p = 8.63 x 10(-9)). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.
C1 [Ayele, Fasil Tekola; Doumatey, Ayo; Huang, Hanxia; Zhou, Jie; Charles, Bashira; Chen, Guanjie; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Erdos, Michael] NHGRI, Genome Technol Branch, Mol Genet Sect, NIH, Bethesda, MD 20892 USA.
[Adeleye, Jokotade; Balogun, Williams] Univ Ibadan, Dept Med, Ibadan, Nigeria.
[Fasanmade, Olufemi; Johnson, Thomas] Univ Lagos, Lagos, Nigeria.
[Oli, Johnnie; Okafor, Godfrey] Univ Nigeria, Teaching Hosp, Enugu, Nigeria.
[Amoah, Albert] Univ Ghana, Sch Med, Dept Med, Accra, Ghana.
[Eghan, Benjamin A., Jr.; Agyenim-Boateng, Kofi; Acheampong, Joseph] Univ Sci & Technol, Dept Med, Kumasi, Ghana.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Herbert, Alan] Boston Univ, Dept Genet & Genom, Boston, MA 02215 USA.
[Gerry, Norman; Christman, Michael] Coriell Inst Med Res, Camden, NJ USA.
RP Ayele, FT (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM ayeleft@mail.nih.gov; rotimic@mail.nih.gov
RI e-, a/F-9947-2012;
OI Adebamowo, Clement/0000-0002-6571-2880; Adeyemo,
Adebowale/0000-0002-3105-3231; Tekola-Ayele, Fasil/0000-0003-4194-9370
FU NIGMS/MBRS/SCORE [S06GM008016-320107, S06GM008016-380111]; National
Center for Research Resources (NCRR), a component of the National
Institutes of Health (NIH) [2M01RR010284]; National Human Genome
Research Institute, National Institutes of Health, in the Center for
Research in Genomics and Global Health [Z01HG200362]; Coriell Institute
for Biomedical Sciences
FX The study was supported by grants S06GM008016-320107 to CR 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), which is supported by grant number
2M01RR010284 from the National Center for Research Resources (NCRR), a
component of the National Institutes of Health (NIH). Additional support
was provided by the Coriell Institute for Biomedical Sciences. This
research was supported in part by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health,
in the Center for Research in Genomics and Global Health (Z01HG200362).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 53
TC 11
Z9 11
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
EI 1432-1211
J9 IMMUNOGENETICS
JI Immunogenetics
PD MAY
PY 2012
VL 64
IS 5
BP 351
EP 359
DI 10.1007/s00251-011-0596-7
PG 9
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 925HC
UT WOS:000302750800002
ER
PT J
AU Pai, VM
Kozlowski, M
Donahue, D
Miller, E
Xiao, XH
Chen, MY
Yu, ZX
Connelly, P
Jeffries, K
Wen, H
AF Pai, Vinay M.
Kozlowski, Megan
Donahue, Danielle
Miller, Elishiah
Xiao, Xianghui
Chen, Marcus Y.
Yu, Zu-Xi
Connelly, Patricia
Jeffries, Kenneth
Wen, Han
TI Coronary artery wall imaging in mice using osmium tetroxide and
micro-computed tomography (micro-CT)
SO JOURNAL OF ANATOMY
LA English
DT Article
DE apolipoprotein E; atherosclerosis; coronary artery wall; micro-computed
tomography; osmium
ID X-RAY MICROTOMOGRAPHY; KNOCKOUT MICE; APOLIPOPROTEIN-E; MOUSE EMBRYOS;
HYPERCHOLESTEROLEMIA; LESIONS
AB The high spatial resolution of micro-computed tomography (micro-CT) is ideal for 3D imaging of coronary arteries in intact mouse heart specimens. Previously, micro-CT of mouse heart specimens utilized intravascular contrast agents that hardened within the vessel lumen and allowed a vascular cast to be made. However, for mouse coronary artery disease models, it is highly desirable to image coronary artery walls and highlight plaques. For this purpose, we describe an ex vivo contrast-enhanced micro-CT imaging technique based on tissue staining with osmium tetroxide (OsO4) solution. As a tissue-staining contrast agent, OsO4 is retained in the vessel wall and surrounding tissue during the fixation process and cleared from the vessel lumens. Its high X-ray attenuation makes the artery wall visible in CT. Additionally, since OsO4 preferentially binds to lipids, it highlights lipid deposition in the artery wall. We performed micro-CT of heart specimens of 5- to 25-week-old C57BL/6 wild-type mice and 5- to 13-week-old apolipoprotein E knockout (apoE-/-) mice at 10 mu m resolution. The results show that walls of coronary arteries as small as 45 mu m in diameter are visible using a table-top micro-CT scanner. Similar image clarity was achieved with 1/2000th the scan time using a synchrotron CT scanner. In 13-week-old apoE mice, lipid-rich plaques are visible in the aorta. Our study shows that the combination of OsO4 and micro-CT permits the visualization of the coronary artery wall in intact mouse hearts.
C1 [Pai, Vinay M.; Kozlowski, Megan; Miller, Elishiah; Wen, Han] NHLBI, Imaging Phys Grp, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Chen, Marcus Y.] NHLBI, Adv Cardiovasc Imaging Grp, NIH, Bethesda, MD 20892 USA.
[Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA.
[Connelly, Patricia] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
[Jeffries, Kenneth] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Donahue, Danielle] NINDS, MIF, NIH, Bethesda, MD 20892 USA.
[Xiao, Xianghui] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
[Miller, Elishiah] Univ Texas El Paso, Dept Comp Sci, El Paso, TX 79968 USA.
RP Wen, H (reprint author), Room B1D416,Bldg 10,MSC 1061,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU Division of Intramural Research of the National Institutes of Health
[HL006142-01]; U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences [DE-AC02-06CH11357]
FX This research was funded by the Division of Intramural Research of the
National Institutes of Health (Project Number HL006142-01 to H.W.). Use
of the Advanced Photon Source at Argonne National Laboratory was
supported by the U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. No
conflicts of interest, financial or otherwise, are declared by the
author(s).
NR 23
TC 13
Z9 13
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-8782
J9 J ANAT
JI J. Anat.
PD MAY
PY 2012
VL 220
IS 5
BP 514
EP 524
DI 10.1111/j.1469-7580.2012.01483.x
PG 11
WC Anatomy & Morphology
SC Anatomy & Morphology
GA 922GX
UT WOS:000302536500009
PM 22360411
ER
PT J
AU Maglinte, GA
Hays, RD
Kaplan, RM
AF Maglinte, Gregory A.
Hays, Ron D.
Kaplan, Robert M.
TI US general population norms for telephone administration of the SF-36v2
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE SF-36; Health-related quality of life; General population norms;
Population survey; Factor analysis; Factor scoring coefficients
ID QUALITY-OF-LIFE; HEALTH SURVEY; SCORES; MODE
AB Objective: US general population norms for mail administration of the Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) were established in 1998. This article reports SF-36v2 telephone-administered norms collected in 2005-2006 for adults aged 35-89 years.
Study Design and Setting: The SF-36v2 was administered to 3,844 adults in the National Health Measurement Study (NHMS), a random-digit dial telephone survey. Scale scores and physical and mental component summary (PCS and MCS) scores were computed.
Results: When compared with 1998 norms (mean = 50.00, standard deviation [SD] = 10.00), SF-36v2 scores for the 2005-2006 general population tended to be higher: physical functioning (mean = 50.68, SD = 14.48); role limitations due to physical health problems (mean = 49.47, SD = 14.71); bodily pain (mean = 50.66, SD = 16.28); general health perceptions (mean = 50.10, SD = 16.87); vitality (mean = 53.71, SD = 15.35); social functioning (mean = 51.37, SD = 13.93); role limitations due to emotional problems (mean = 51.44, SD = 13.93); mental health (mean = 54.27, SD = 13.28); PCS (mean = 49.22, SD = 15.13); MCS (mean = 53.78, SD = 13.14). PCS and MCS factor scoring coefficients were similar to those previously reported for the 1998 norms. SF-36v2 norms for telephone administration were created.
Conclusion: The higher scores for NHMS data are likely due to the effect of telephone administration. The 2005-2006 norms can be used as a reference to interpret scale and component summary scores for telephone-administered surveys with the SF-36v2. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Maglinte, Gregory A.; Hays, Ron D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA.
[Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP Maglinte, GA (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA.
EM greg.maglinte@ucla.edu
RI Hays, Ronald/D-5629-2013
FU National Institute on Aging [P01-AG020679, P30AG021684, P30-AG028748];
NCMHD [P20MD000182]
FX This research was supported by a grant from the National Institute on
Aging (P01-AG020679). Hays and Kaplan were also supported in part by NIA
grants (P30AG021684 and P30-AG028748), and Hays had partial support from
NCMHD (P20MD000182).
NR 19
TC 23
Z9 24
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD MAY
PY 2012
VL 65
IS 5
BP 497
EP 502
DI 10.1016/j.jclinepi.2011.09.008
PG 6
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 920ZJ
UT WOS:000302447500007
PM 22269331
ER
PT J
AU Eberlein, M
Arnaoutakis, GJ
Yarmus, L
Feller-Kopman, D
Dezube, R
Chahla, MF
Bolukbas, S
Reed, RM
Klesney-Tait, J
Parekh, KR
Merlo, CA
Shah, AS
Orens, JB
Brower, RG
AF Eberlein, Michael
Arnaoutakis, George J.
Yarmus, Lonny
Feller-Kopman, David
Dezube, Rebecca
Chahla, Mayy F.
Bolukbas, Servet
Reed, Robert M.
Klesney-Tait, Julia
Parekh, Kalpaj R.
Merlo, Christian A.
Shah, Ashish S.
Orens, Jonathan B.
Brower, Roy G.
TI The effect of lung size mismatch on complications and resource
utilization after bilateral lung transplantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE lung transplantation; lung size mismatch; resource utilization; airway
complications
ID PRIMARY GRAFT DYSFUNCTION; AIRWAY COMPLICATIONS; PULMONARY-FIBROSIS;
UNITED-STATES; CAPACITY; IMPACT; DYSANAPSIS; PRESSURE; STRESS; FLOW
AB BACKGROUND: Oversizing the lung allograft, as estimated by a donor-to-recipient predicted total lung capacity (pTLC) ratio > 1.0, was associated with improved long-term survival after lung transplantation (LTx) but could be associated with increased post-operative complications and higher resource utilization.
METHODS: The prospectively maintained LTx database at The Johns Hopkins Hospital was retrospectively reviewed for bilateral LTx patients in the post-Lung Allocation Score (LAS) era. Patients were grouped by pTLC ratio 1.0 (undersized) or > 1.0 (oversized). Post-operative complications and hospital charges were analyzed.
RESULTS: The pTLC ratio was available for 70 patients: 31 were undersized and 39 oversized. Undersized patients had a higher LAS (40.4 vs 35.8, p = 0.009), were more often in the intensive care unit (ICU) pre-LTx (35% vs 10%, p = 0.01), and had a higher occurrence of primary graft dysfunction (POD; 25% vs 5%, p = 0.013) and tracheostomy (32% vs 10%, p = 0.02), longer index hospitalizations (20 [interquartile range (IQR), 10-46] vs 16 [IQR, 12-251 days, p = 0.048), and higher index; hospitalization charges ($176,247 [IQR, $137,646 $284,0 I 2] vs $158,492 [IQR, $136,250 4191,301], p = 0.04). After adjusting for LAS and pre-LTx ICU stay, a lower pTLC ratio remained associated with higher hospital charges (p = 0.049). Airway complications were more frequent and severe in undersized patients.
CONCLUSION: Oversized allografts were not associated with an increase in post-LTx complications. However, LTx recipients of undersized allografts were more likely to experience POD, tracheostomy, and had higner resource utilization. Higher acuity in the undersized group might explain these findings; however, multivariate models suggest an independent association between undersizing, PGD, and resource utilization. J Heart Lung Transplant 2012;31:492-500 (C) Published by Elsevier Inc. on behalf of the International Society for Heart and Lung Transplantation.
C1 [Eberlein, Michael; Yarmus, Lonny; Feller-Kopman, David; Merlo, Christian A.; Orens, Jonathan B.; Brower, Roy G.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Eberlein, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Dezube, Rebecca] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Arnaoutakis, George J.; Shah, Ashish S.] Johns Hopkins Univ, Sch Med, Div Cardiac Surg, Baltimore, MD USA.
[Chahla, Mayy F.] Johns Hopkins Univ, Sch Med, Div Hosp Med, Baltimore, MD USA.
[Bolukbas, Servet] Dr Horst Schmidt Klin, Dept Thorac Surg, Wiesbaden, Germany.
[Reed, Robert M.] Univ Maryland, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Klesney-Tait, Julia; Parekh, Kalpaj R.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
RP Eberlein, M (reprint author), Univ Iowa, Carver Coll Med, Div Pulm Crit Care & Occupat Med, 200 Hawkins Dr, Iowa City, IA 52242 USA.
EM michael-eberlein@uiowa.edu
RI Parekh, Kalpaj/E-4966-2012;
OI Shah, Ashish/0000-0002-1821-9110
NR 30
TC 29
Z9 29
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD MAY
PY 2012
VL 31
IS 5
BP 492
EP 500
DI 10.1016/j.healun.2011.12.009
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 925JE
UT WOS:000302756700009
PM 22325691
ER
PT J
AU Groninger, H
Phillips, JM
AF Groninger, Hunter
Phillips, Jayne M.
TI Gross Hematuria Assessment and Management at the End of Life
SO JOURNAL OF HOSPICE & PALLIATIVE NURSING
LA English
DT Article
DE goals of care; gross hematuria; hospice; palliative; pain management;
urology
ID URETHRAL CATHETERIZATION; FLEXIBLE CYSTOSCOPY; PAIN; EMBOLIZATION;
PATIENT; RELIEF
AB A distressing complication for patients and families, gross hematuria at the end of life challenges hospice and palliative care clinicians to utilize skills in medical and nursing management, communication and clarification of patient goals, and relief of symptom burden. Massive hemorrhage in the genitourinary tract can radically alter the terminal trajectory for patients and necessitate intensive interventions aimed at promoting comfort. Here, a case of gross hematuria in an adult hospice patient serves to broaching decision-making challenges and management strategies.
C1 [Groninger, Hunter; Phillips, Jayne M.] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Groninger, H (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, Bldg 10,Room 2-1733,MSC 1517, Bethesda, MD 20892 USA.
EM hunter.groninger@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 19
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1522-2179
J9 J HOSP PALLIAT NURS
JI J. Hosp. Palliat. Nurs.
PD MAY
PY 2012
VL 14
IS 3
BP 184
EP 188
DI 10.1097/NJH.0b013e31824fc169
PG 5
WC Nursing
SC Nursing
GA 925OH
UT WOS:000302770200003
PM 24826082
ER
PT J
AU Tayo, BO
Luke, A
McKenzie, CA
Kramer, H
Cao, G
Durazo-Arvizu, R
Forrester, T
Adeyemo, AA
Cooper, RS
AF Tayo, B. O.
Luke, A.
McKenzie, C. A.
Kramer, H.
Cao, G.
Durazo-Arvizu, R.
Forrester, T.
Adeyemo, A. A.
Cooper, R. S.
TI Patterns of sodium and potassium excretion and blood pressure in the
African Diaspora
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
DE blood pressure; sodium excretion; potassium excretion; African Diaspora
ID SALT INTAKE; DIETARY-SODIUM; CARDIOVASCULAR-DISEASE; RACIAL-DIFFERENCES;
HYPERTENSION; METAANALYSIS; ASSOCIATION; REDUCTION; CHILDREN; HUMANS
AB Habitual levels of dietary sodium and potassium are correlated with age-related increases in blood pressure (BP) and likely have a role in this phenomenon. Although extensive published evidence exists from randomized trials, relatively few large-scale community surveys with multiple 24-h urine collections have been reported. We obtained three 24-h samples from 2704 individuals from Nigeria, Jamaica and the United States to evaluate patterns of intake and within-person relationships with BP. The average (+/- s.d.) age and weight of the participants across all the three sites were 39.9 +/- 8.6 years and 76.1 +/- 21.2 kg, respectively, and 55% of the total participants were females. Sodium excretion increased across the East-West gradient (for example, 123.9 +/- 54.6, 134.1 +/- 48.8, 176.6 +/- 71.0 (+/- s.d.) mmol, Nigeria, Jamaica and US, respectively), whereas potassium was essentially unchanged (for example, 46.3 +/- 22.9, 40.7 +/- 16.1, 44.7 +/- 16.4 (+/- s.d.) mmol, respectively). In multivariate analyses both sodium (positively) and potassium (negatively) were strongly correlated with BP (P<0.001); quantitatively the association was stronger, and more consistent in each site individually, for potassium. The within-population day-to-day variation was also greater for sodium than for potassium. Among each population group, a significant correlation was observed between sodium and urine volume, supporting the prior finding of sodium as a determinant of fluid intake in free-living individuals. These data confirm the consistency with the possible role of dietary electrolytes as hypertension risk factors, reinforcing the relevance of potassium in these populations. Journal of Human Hypertension (2012) 26, 315-324; doi:10.1038/jhh.2011.39; published online 19 May 2011
C1 [Tayo, B. O.; Luke, A.; Kramer, H.; Cao, G.; Durazo-Arvizu, R.; Cooper, R. S.] Loyola Univ Chicago, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA.
[McKenzie, C. A.; Forrester, T.] Univ W Indies, Trop Metab Res Unit, Kingston 7, Jamaica.
[Adeyemo, A. A.] Univ Ibadan, Coll Med, Inst Child Hlth, Dept Pediat, Ibadan, Nigeria.
[Adeyemo, A. A.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
RP Cooper, RS (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Prevent Med & Epidemiol, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM rcooper@lumc.edu
OI Kramer, Holly/0000-0002-6374-837X; Adeyemo,
Adebowale/0000-0002-3105-3231
FU National Institutes of Health [R37HL045508, R01HL 053353]
FX This work was supported by the National Institutes of Health, grant
numbers R37HL045508 and R01HL 053353.
NR 38
TC 12
Z9 12
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD MAY
PY 2012
VL 26
IS 5
BP 315
EP 324
DI 10.1038/jhh.2011.39
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 925WD
UT WOS:000302791800005
PM 21593783
ER
PT J
AU Puronen, CE
Thompson, WL
Imamichi, H
Beq, S
Hodge, JN
Rehm, C
Parker, R
DerSimonian, R
Brenchley, JM
Sereti, I
AF Puronen, Camille E.
Thompson, William L.
Imamichi, Hiromi
Beq, Stephanie
Hodge, Jessica N.
Rehm, Catherine
Parker, Raphaelle
DerSimonian, Rebecca
Brenchley, Jason M.
Sereti, Irini
TI Decreased Interleukin 7 Responsiveness of T Lymphocytes in Patients With
Idiopathic CD4 Lymphopenia
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CELL HOMEOSTASIS; IL-7 PROMOTES; RECEPTOR; MEMORY; PROLIFERATION;
EXPRESSION; INCREASES; SUPPRESSION; MECHANISM; INFECTION
AB Background. Elevated serum interleukin 7 (IL-7) levels are observed in lymphopenic conditions, including idiopathic CD4 lymphopenia (ICL), which is characterized by CD4 lymphopenia in the absence of human immunodeficiency virus infection or other known immunodeficiency.
Methods. To test whether defective IL-7 signaling could be an etiologic or contributing factor in ICL, peripheral blood mononuclear cells from patients with ICL (median CD4 T-cell count, 160 cells/mu L) and healthy controls (median CD4 T-cell count, 582 cells/mu L) were evaluated for expression of IL-7R alpha chain (CD127) and intracellular phosphorylated STAT-5 (a marker of gamma c cytokine signaling) after cytokine stimulation. Gene expression was analyzed by real-time polymerase chain reaction following IL-7 stimulation.
Results. The percentage of CD4+CD127+ T cells was lower in patients with ICL, compared with controls (P < .001). Lower levels of STAT-5 phosphorylation after IL-7 stimulation were observed in both CD4 and CD8 T cells from patients with ICL, compared with controls (P < .001 and P = .017, respectively), that inversely correlated in CD4 T cells with serum IL-7 levels (r = -0.734, P = .013). Destabilization of p27(kip1), a critical step for IL-7-induced T-cell cycling, was decreased in patients with ICL, compared with controls (P = .004), after IL-7 stimulation.
Conclusions. These data suggest that diminished responsiveness to IL-7 in CD4 and CD8 T cells during ICL may be contributing to the dysregulation of T-cell homeostasis.
C1 [Puronen, Camille E.; Thompson, William L.; Imamichi, Hiromi; Hodge, Jessica N.; Rehm, Catherine; Parker, Raphaelle; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[DerSimonian, Rebecca] NIAID, Biostat Branch, NIH, Bethesda, MD 20892 USA.
[Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Beq, Stephanie] Cytheris SA, Issy Les Moulineaux, France.
RP Sereti, I (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10 Magnuson Clin Ctr,Room 11B07A, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases at the National
Institutes of Health (NIH); National Cancer Institute, NIH
[HHSN261200800001E]; NIH; Pfizer
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases at the
National Institutes of Health (NIH). Additionally, this project has also
been funded in part with federal funds from the National Cancer
Institute, NIH (grant HHSN261200800001E). C. E. P. was a participant in
the NIH Clinical Research Training Program, a public-private partnership
supported jointly by the NIH and Pfizer.
NR 37
TC 10
Z9 10
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2012
VL 205
IS 9
BP 1382
EP 1390
DI 10.1093/infdis/jis219
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 921QI
UT WOS:000302491800008
PM 22454463
ER
PT J
AU Hubbard, JJ
Greenwell-Wild, T
Barrett, L
Yang, J
Lempicki, RA
Wahl, SM
Asmuth, DM
Murphy, RL
Pollard, RB
Kottilil, S
AF Hubbard, Jonathan J.
Greenwell-Wild, Teresa
Barrett, Lisa
Yang, Jun
Lempicki, Richard A.
Wahl, Sharon M.
Asmuth, David M.
Murphy, Robert L.
Pollard, Richard B.
Kottilil, Shyam
TI Host Gene Expression Changes Correlating With Anti-HIV-1 Effects in
Human Subjects After Treatment With Peginterferon Alfa-2a
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; PEGYLATED INTERFERON;
RIBAVIRIN; REPLICATION; TRIAL; BETA
AB We investigated whether interferon-inducible genes (IFIGs) with known anti-human immunodeficiency virus (HIV) activity in vitro were associated with in vivo virological response in HIV infection. Nine untreated HIV-1-infected volunteers were treated for 12 weeks with peginterferon alfa-2a. A subset of IFIGs (23 of 47) increased compared with baseline through 6 weeks beyond therapy, and 10 of the 23 IFIGs significantly inversely correlated (r = 5 20.7; P < .05) with virological response. The strength of peginterferon alfa-2-ainduced IFIG response significantly correlated with declines in HIV load during treatment (r(2) = 0.87, p = .003). This study links HIV virological response to a specific IFIG subset, a potential prognostic indicator in peginterferon alfa-2a-treated patients with HIV infection.
C1 [Hubbard, Jonathan J.; Barrett, Lisa; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Greenwell-Wild, Teresa; Wahl, Sharon M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
[Yang, Jun; Lempicki, Richard A.] SAIC Frederick Inc, Frederick, MD USA.
[Asmuth, David M.; Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
[Murphy, Robert L.] Northwestern Univ, Evanston, IL USA.
RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 11N204,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Murphy,
Robert/0000-0003-3936-2052
FU National Institutes of Health (NIH) [1U01-AI068636, 1U01-AI068634,
1U01-AI069471, 1U01-AI069432, 1U01-AI069484, 201IC001, 204IC006]; NIH;
Pfizer Inc
FX This work was supported by the National Institutes of Health (NIH)
(grant 1U01-AI068636 to the ACTG; grant 1U01-AI068634 to the ACTG
Statistical and Data Analysis Center; grant 1U01-AI069471 to
Northwestern University; grant 1U01-AI069432 to University of
California, San Diego; grant 1U01-AI069484 to Duke University;
Immunology Support Laboratory grant 201IC001 to University of
California-Davis; and Immunology Support Laboratory grant 204IC006 to
University of Pittsburgh, and the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Disease and the
National Institute of Dental and Craniofacial Research). The
participation of J. J. H. was made possible by the Clinical Research
Training Program, a public-private partnership supported jointly by the
NIH and Pfizer Inc (via a grant to the foundation for NIH from Pfizer).
NR 15
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2012
VL 205
IS 9
BP 1443
EP 1447
DI 10.1093/infdis/jis211
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 921QI
UT WOS:000302491800015
PM 22454462
ER
PT J
AU Wheless, L
Kistner-Griffin, E
Jorgensen, TJ
Ruczinski, I
Berthier-Schaad, Y
Kessing, B
Hoffman-Bolton, J
Francis, L
Shugart, YY
Strickland, PT
Kao, WHL
Alani, RM
Smith, MW
Alberg, AJ
AF Wheless, Lee
Kistner-Griffin, Emily
Jorgensen, Timothy J.
Ruczinski, Ingo
Berthier-Schaad, Yvette
Kessing, Bailey
Hoffman-Bolton, Judith
Francis, Lesley
Shugart, Yin Yao
Strickland, Paul T.
Kao, W. H. Linda
Alani, Rhoda M.
Smith, Michael W.
Alberg, Anthony J.
TI A Community-Based Study of Nucleotide Excision Repair Polymorphisms in
Relation to the Risk of Non-Melanoma Skin Cancer
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID BASAL-CELL CARCINOMA; XERODERMA-PIGMENTOSUM; DNA-DAMAGE;
MOLECULAR-ORIGINS; COMMON VARIANTS; SUN EXPOSURE; GENE XPD; ASSOCIATION;
MELANOMA; PROTEIN
AB Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n = 900) were matched to controls (n = 900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
C1 [Kistner-Griffin, Emily; Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Wheless, Lee; Kistner-Griffin, Emily; Francis, Lesley; Alberg, Anthony J.] Med Univ S Carolina, Dept Med, Div Epidemiol & Biostat, Charleston, SC 29425 USA.
[Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA.
[Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Berthier-Schaad, Yvette; Kessing, Bailey] NCI Frederick, Lab Genom Divers, Frederick, MD USA.
[Berthier-Schaad, Yvette; Strickland, Paul T.; Kao, W. H. Linda; Alberg, Anthony J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Hoffman-Bolton, Judith] George W Comstock Ctr Publ Hlth Res & Prevent, Washington Cty, MD USA.
[Shugart, Yin Yao] NIMH, Div Intramural Res Programs, Rockville, MD 20857 USA.
[Strickland, Paul T.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Alani, Rhoda M.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA.
[Smith, Michael W.] SAIC Frederick Inc, Genet & Genom Grp, Adv Technol Program, NCI Frederick, Frederick, MD USA.
RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, 68 President St,MSC 955, Charleston, SC 29425 USA.
EM alberg@musc.edu
OI Alani, Rhoda/0000-0003-2741-2665
FU National Cancer Institute [R01 CA105069]; NIH/NCCR [TL1 RR029881]; Abney
Family Foundation; National Cancer Institute, National Institutes of
Health [N01-CO-12400]
FX This research was made possible by funding from the National Cancer
Institute (R01 CA105069), NIH/NCCR (TL1 RR029881), and the Abney Family
Foundation. 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. The project described in this
article has been funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
N01-CO-12400.
NR 42
TC 10
Z9 10
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
IS 5
BP 1354
EP 1362
DI 10.1038/jid.2012.4
PG 9
WC Dermatology
SC Dermatology
GA 926UA
UT WOS:000302856200011
PM 22336945
ER
PT J
AU Makrogiannis, S
Serai, S
Fishbein, KW
Schreiber, C
Ferrucci, L
Spencer, RG
AF Makrogiannis, Sokratis
Serai, Suraj
Fishbein, Kenneth W.
Schreiber, Catherine
Ferrucci, Luigi
Spencer, Richard G.
TI Automated quantification of muscle and fat in the thigh from water-,
fat-, and nonsuppressed MR images
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE body composition; image segmentation; thigh imaging
ID INTERMUSCULAR ADIPOSE-TISSUE; MAGNETIC-RESONANCE IMAGES; SEGMENTATION;
OBESITY
AB Purpose: To introduce and validate an unsupervised muscle and fat quantification algorithm based on joint analysis of water-suppressed (WS), fat-suppressed (FS), and water and fat (nonsuppressed) volumetric magnetic resonance imaging (MRI) of the mid-thigh region. Materials and Methods: We first segmented the subcutaneous fat by use of a parametric deformable model, then applied centroid clustering in the feature domain defined by the voxel intensities in WS and FS images to identify the intermuscular fat and muscle. In the final step we computed volumetric and area measures of fat and muscle. We applied this algorithm on datasets of water-, fat-, and nonsuppressed volumetric MR images acquired from 28 participants. Results: We validated our tissue composition analysis against fat and muscle area measurements obtained from semimanual analysis of single-slice mid-thigh computed tomography (CT) images of the same participants and found very good agreement between the two methods. Furthermore, we compared the proposed approach with a variant that uses nonsuppressed images only and observed that joint analysis of WS and FS images is more accurate than the nonsuppressed only variant. Conclusion: Our MRI algorithm produces accurate tissue quantification, is less labor-intensive, and more reproducible than the original CT-based workflow and can address interparticipant anatomic variability and intensity inhomogeneity effects.
C1 [Makrogiannis, Sokratis; Serai, Suraj; Fishbein, Kenneth W.; Schreiber, Catherine; Ferrucci, Luigi; Spencer, Richard G.] NIA, NIH, Baltimore, MD 21225 USA.
RP Makrogiannis, S (reprint author), NIA, NIH, 3001 S Hanover St,5th Fl, Baltimore, MD 21225 USA.
EM makrogianniss@mail.nih.gov
OI Fishbein, Kenneth/0000-0002-6353-4603
FU Intramural NIH HHS [Z99 AG999999]
NR 25
TC 15
Z9 15
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAY
PY 2012
VL 35
IS 5
BP 1152
EP 1161
DI 10.1002/jmri.22842
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 924WK
UT WOS:000302721800020
PM 22170747
ER
PT J
AU Madsen, DH
Jurgensen, HJ
Ingvarsen, S
Melander, MC
Vainer, B
Egerod, KL
Hald, A
Rono, B
Madsen, CA
Bugge, TH
Engelholm, LH
Behrendt, N
AF Madsen, Daniel H.
Jurgensen, Henrik J.
Ingvarsen, Signe
Melander, Maria C.
Vainer, Ben
Egerod, Kristoffer L.
Hald, Andreas
Rono, Birgitte
Madsen, Charlotte A.
Bugge, Thomas H.
Engelholm, Lars H.
Behrendt, Niels
TI Endocytic collagen degradation: a novel mechanism involved in protection
against liver fibrosis
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE matrix remodelling; uPARAP; Endo180; knockout mouse; mannose receptor;
liver disease model; endocytosis; matrix metalloproteinase; HSC; MRC2
ID MACROPHAGE MANNOSE RECEPTOR; HEPATIC STELLATE CELLS; MATRIX
METALLOPROTEINASES; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX;
TRANSMEMBRANE GLYCOPROTEIN; PROTEIN UPARAP/ENDO180; DENATURED COLLAGEN;
ENDOTHELIAL-CELLS; MEMBRANE-PROTEINS
AB Fibrosis of the liver and its end-stage, cirrhosis, represent major health problems worldwide. In these fibrotic conditions, activated fibroblasts and hepatic stellate cells display a net deposition of collagen. This collagen deposition is a major factor leading to liver dysfunction, thus making it crucially important to understand both the collagen synthesis and turnover mechanisms in this condition. Here we show that the endocytic collagen receptor, uPARAP/Endo180, is a major determinant in governing the balance between collagen deposition and degradation. Cirrhotic human livers displayed a marked up-regulation of uPARAP/Endo180 in activated fibroblasts and hepatic stellate cells located close to the collagen deposits. In a hepatic stellate cell line, uPARAP/Endo180 was shown to be active in, and required for, the uptake and intracellular degradation of collagen. To evaluate the functional importance of this collagen receptor in vivo, liver fibrosis was induced in uPARAP/Endo180-deficient mice and littermate wild-type mice by chronic CCl4 administration. A strong up-regulation of uPARAP/Endo180 was observed in wild-type mice, and a quantitative comparison of collagen deposits in the two groups of mice clearly revealed a fibrosis protective role of uPARAP/Endo180. This effect appeared to directly reflect the activity of the collagen receptor, since no compensatory events were noted when comparing the mRNA expression profiles of the two groups of mice in an array system focused on matrix-degrading components. This function of uPARAP/Endo180 defines a novel role of intracellular collagen turnover in fibrosis protection. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Madsen, Daniel H.; Jurgensen, Henrik J.; Ingvarsen, Signe; Melander, Maria C.; Madsen, Charlotte A.; Engelholm, Lars H.; Behrendt, Niels] Univ Copenhagen, Rigshosp, Finsen Lab, BRIC, DK-1168 Copenhagen, Denmark.
[Ingvarsen, Signe] Univ Copenhagen, Dept Biol, DK-1168 Copenhagen, Denmark.
[Vainer, Ben] Rigshosp, Dept Pathol, DK-2200 Copenhagen N, Denmark.
[Egerod, Kristoffer L.] Univ Copenhagen, Dept Neurosci & Pharmacol, DK-1168 Copenhagen, Denmark.
[Hald, Andreas; Rono, Birgitte] Univ Copenhagen, Dept Cellular & Mol Med, DK-1168 Copenhagen, Denmark.
[Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Behrendt, N (reprint author), Rigshosp, Copenhagen Bioctr, Finsen Lab BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark.
EM niels.behrendt@finsenlab.dk
RI Egerod, Kristoffer/D-9481-2012;
OI Egerod, Kristoffer/0000-0003-2781-1594; Madsen, Daniel
Hargboel/0000-0002-3183-6201; Engelholm, Lars/0000-0002-6616-1232
FU Danish Cancer Society; Danish Medical Research Council; Danish Cancer
Research Foundation; Lundbeck Foundation; Danish National Research
Foundation (Danish-Chinese Centre for Proteases and Cancer); European
Community [201279]; Grosserer Alfred Nielsen og Hustrus Foundation;
NIDCR; Copenhagen University Hospital; University of Copenhagen, Faculty
of Science
FX The excellent technical assistance of Suzanne K. Moller, Katharina H.
Stegmann, Agnieszka Ingvorsen and Mette M. Andersen and the expert
assistance at the Core facility for Integrated Microcopy, Faculty of
Health Sciences, University of Copenhagen, is gratefully acknowledged.
We thank Dr Marcos Rojkind for generously providing the CFSC-2G cells.
This work was supported by the Danish Cancer Society, the Danish Medical
Research Council, the Danish Cancer Research Foundation, the Lundbeck
Foundation, the Danish National Research Foundation (Danish-Chinese
Centre for Proteases and Cancer) and the European Community's Seventh
Framework Programme FP7/2007-2011 (under Grant Agreement No. 201279 to
NB), by the Lundbeck Foundation and the Grosserer Alfred Nielsen og
Hustrus Foundation (to LHE), and by the NIDCR Intramural Research
Program (to THB). The work was also supported by personal grants from
Copenhagen University Hospital (to DHM and HJJ), the Lundbeck Foundation
(to DHM) and the University of Copenhagen, Faculty of Science (to SI).
NR 59
TC 16
Z9 17
U1 1
U2 29
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD MAY
PY 2012
VL 227
IS 1
BP 94
EP 105
DI 10.1002/path.3981
PG 12
WC Oncology; Pathology
SC Oncology; Pathology
GA 921IF
UT WOS:000302470600011
PM 22294280
ER
PT J
AU Hautvast, GLTF
Salton, CJ
Chuang, ML
Breeuwer, M
O'Donnell, CJ
Manning, WJ
AF Hautvast, Gilion L. T. F.
Salton, Carol J.
Chuang, Michael L.
Breeuwer, Marcel
O'Donnell, Christopher J.
Manning, Warren J.
TI Accurate computer-aided quantification of left ventricular parameters:
Experience in 1555 cardiac magnetic resonance studies from the
Framingham Heart Study
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE segmentation; postprocessing; technique development; technical research
ID MR-IMAGES; SEGMENTATION; APPEARANCE; PROPAGATION
AB Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 +/- 1.7 min for an average of 221 +/- 36 myocardial contours per participant. This included 4.8 +/- 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 +/- 4.1 mL for end-diastolic volume, -0.3 +/- 2.9 mL for end-systolic volume, 0.7 +/- 3.1 mL for stroke volume, and 0.3 +/- 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Healthcare, Imaging Syst, MR, NL-5680 DA Best, Netherlands.
[Salton, Carol J.; Chuang, Michael L.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Salton, Carol J.; Chuang, Michael L.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Chuang, Michael L.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Breeuwer, Marcel] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Hautvast, GLTF (reprint author), Philips Healthcare, Imaging Syst, MR, Veenpluis 4-6, NL-5680 DA Best, Netherlands.
EM gilion.hautvast@philips.com; marcel.breeuwer@philips.com
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institutes of Health [N01-HC-25195, RO1
HL70279]; Philips Healthcare
FX Grant sponsor: National Heart, Lung and Blood Institute's Framingham
Heart Study; Grant number: N01-HC-25195; Grant sponsor: National
Institutes of Health; Grant number: N01-HC-25195 is a subcontract of RO1
HL70279; Grant sponsor: unrestricted grant from Philips Healthcare.
NR 25
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAY
PY 2012
VL 67
IS 5
BP 1478
EP 1486
DI 10.1002/mrm.23127
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 923KY
UT WOS:000302619400029
PM 22021128
ER
PT J
AU Guerreiro, RJ
Lohmann, E
Kinsella, E
Bras, JM
Luu, N
Gurunlian, N
Dursun, B
Bilgic, B
Santana, I
Hanagasi, H
Gurvit, H
Gibbs, JR
Oliveira, C
Emre, M
Singleton, A
AF Guerreiro, Rita Joao
Lohmann, Ebba
Kinsella, Emma
Bras, Jose Miguel
Luu, Nga
Gurunlian, Nicole
Dursun, Burcu
Bilgic, Basar
Santana, Isabel
Hanagasi, Hasmet
Gurvit, Hakan
Gibbs, Jesse Raphael
Oliveira, Catarina
Emre, Murat
Singleton, Andrew
TI Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3
mutation in a Turkish family with Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; NOTCH3; CADASIL; Exome sequencing
ID CADASIL PATIENTS; LEUKOENCEPHALOPATHY; DIAGNOSIS; SPECTRUM; STROKE
AB Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP. PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any additional pathogenic mutations. Although the complex history of disease in this family precluded us to establish segregation of the mutation found with disease, our results show that exome sequencing is a rapid, cost-effective and comprehensive tool to detect genetic mutations, allowing for the identification of unexpected genetic causes of clinical phenotypes. As etiological based therapeutics become more common, this method will be key in diagnosing and treating disease. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Singleton, Andrew] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Guerreiro, Rita Joao; Bras, Jose Miguel; Oliveira, Catarina] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Guerreiro, Rita Joao; Bras, Jose Miguel; Gurunlian, Nicole; Gibbs, Jesse Raphael] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Lohmann, Ebba; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat] Istanbul Univ, Dept Neurol, Istanbul Fac Med, Istanbul, Turkey.
[Kinsella, Emma] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales.
[Dursun, Burcu] Istanbul Univ, Inst Expt Med, Istanbul, Turkey.
[Santana, Isabel; Oliveira, Catarina] Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal.
RP Singleton, A (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A1014,35 Convent Dr, Bethesda, MD 20892 USA.
EM Singleta@mail.nih.gov
RI bilgic, basar/E-4821-2012; Singleton, Andrew/C-3010-2009; Bras,
Jose/A-1428-2011;
OI Bras, Jose/0000-0001-8186-0333; Oliveira, Catarina/0000-0001-6942-4328;
Santana, Isabel/0000-0002-8114-9434
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [Z01 AG000950-06]; National Institute on
Aging (NIA) [U24 AG21886]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services, project number Z01 AG000950-06.
Samples from the National Cell Repository for Alzheimer's Disease
(NCRAD), which receives government support under a cooperative agreement
grant (U24 AG21886) awarded by the National Institute on Aging (NIA),
were used in this study. We thank contributors, including the
Alzheimer's Disease Centers, who collected samples used in this study,
as well as patients and their families, whose help and participation
made this work possible. Samples from the Human Genetics Resource Center
DNA and Cell Line Repository (ccr.coriell.org) were also used.
NR 25
TC 6
Z9 8
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2012
VL 33
IS 5
AR 1008.e17
DI 10.1016/j.neurobiolaging.2011.10.009
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 921OF
UT WOS:000302486200033
PM 22153900
ER
PT J
AU Boyd, AS
Rodrigues, NP
Lui, KO
Fu, XM
Xu, Y
AF Boyd, Ashleigh S.
Rodrigues, Neil P.
Lui, Kathy O.
Fu, Xuemei
Xu, Yang
TI Concise Review: Immune Recognition of Induced Pluripotent Stem Cells
SO STEM CELLS
LA English
DT Article
DE Stem cells; Embryonic stem cells; Induced pluripotent stem cells; Cell
replacement therapy; Immunogenicity; Transplantation; Tolerance;
Rejection; Regenerative medicine
ID REGULATORY T-CELLS; LONG-TERM ACCEPTANCE; HUMAN SOMATIC-CELLS;
DIFFERENTIATED DERIVATIVES; COSTIMULATION BLOCKADE; CARDIAC ALLOGRAFTS;
DENDRITIC CELLS; DEFINED FACTORS; BLOCKING CD40; CD28 PATHWAYS
AB Autologous-induced pluripotent stem cells (iPSCs) may eventually be used in cell replacement therapies to treat a wide range of diseases and have been touted as a solution to the vexing problem of immune rejection in this context. Emerging evidence suggests, however, that ostensibly histocompatible iPSCs may be rejected following transplantation. Here, we review the mechanisms that contribute to immunogenicity in iPSCs and forward approaches to permit their acceptance in potential cell replacement therapies. STEM CELLS 2012;30:797803
C1 [Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, NIH, Ctr Biomed Res Excellence COBRE Stem Cell Biol, Roger Williams Canc Med Ctr,Sch Med, Providence, RI 02908 USA.
[Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA.
[Boyd, Ashleigh S.; Rodrigues, Neil P.] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA.
[Lui, Kathy O.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Boston, MA USA.
[Fu, Xuemei; Xu, Yang] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
[Fu, Xuemei] Chengdu Womens & Childrens Cent Hosp, Chengdu, Sichuan, Peoples R China.
RP Boyd, AS (reprint author), Boston Univ, NIH, COBRE, Roger Williams Canc Med Ctr,Sch Med,Prior Off 207, 825 Chalkstone Ave, Providence, RI 02908 USA.
EM asboyd@bu.edu; yangxu@ucsd.edu
RI Lui, Kathy O./E-4883-2015
OI Lui, Kathy O./0000-0002-1616-3643
FU NIH [P20RR018757]; Rhode Island Foundation; BD Biosciences; NSFC
[30872346]; California Institute for Regenerative Medicine [TR1-01277];
NIH COBRE at Roger Williams Medical Center
FX This work was supported by NIH Grant P20RR018757 (A.S.B. and N.P.R.),
Rhode Island Foundation (A.S.B.), BD Biosciences (N.P.R.), a NSFC Grant
30872346 (X.F.), and California Institute for Regenerative Medicine
Grant TR1-01277 (Y.X.). Additional support to A.S.B. and N.P.R.
laboratories is provided by the administrative and flow cytometry cores
within the NIH COBRE at Roger Williams Medical Center.
NR 53
TC 26
Z9 27
U1 1
U2 14
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 MAY
PY 2012
VL 30
IS 5
BP 797
EP 803
DI 10.1002/stem.1066
PG 7
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 923KD
UT WOS:000302617300001
PM 22419544
ER
PT J
AU Kele, J
Andersson, ER
Villaescusa, JC
Cajanek, L
Parish, CL
Bonilla, S
Toledo, EM
Bryja, V
Rubin, JS
Shimono, A
Arenas, E
AF Kele, Julianna
Andersson, Emma R.
Villaescusa, J. Carlos
Cajanek, Lukas
Parish, Clare L.
Bonilla, Sonia
Toledo, Enrique M.
Bryja, Vitezslav
Rubin, Jeffrey S.
Shimono, Akihiko
Arenas, Ernest
TI SFRP1 and SFRP2 Dose-Dependently Regulate Midbrain Dopamine Neuron
Development In Vivo and in Embryonic Stem Cells
SO STEM CELLS
LA English
DT Article
DE Embryonic stem cells; Neural differentiation; Developmental biology;
Parkinson's disease
ID FRIZZLED-RELATED PROTEIN-1; DISHEVELLED PHOSPHORYLATION; INCREASES
DIFFERENTIATION; INT-1 PROTOONCOGENE; PARKINSONS-DISEASE; SPEMANN
ORGANIZER; WNT/BETA-CATENIN; WNT ANTAGONIST; NERVOUS-SYSTEM; MOUSE
AB Secreted Frizzled related proteins (sFRPs) are a family of proteins that modulate Wnt signaling, which in turn regulates multiple aspects of ventral midbrain (VM) and dopamine (DA) neuron development. However, it is not known which Wnt signaling branch and what aspects of midbrain DA neuron development are regulated by sFRPs. Here, we show that sFRP1 and sFRP2 activate the Wnt/planar-cell-polarity/Rac1 pathway in DA cells. In the developing VM, sFRP1 and sFRP2 are expressed at low levels, and sFRP1-/- or sFRP2-/- mice had no detectable phenotype. However, compound sFRP1-/-;sFRP2-/- mutants revealed a Wnt/PCP phenotype similar to that previously described for Wnt5a-/- mice. This included an anteroposterior shortening of the VM, a lateral expansion of the Shh domain and DA lineage markers (Lmx1a and Th), as well as an accumulation of Nurr1+ precursors in the VM. In vitro experiments showed that, while very high concentrations of SFRP1 had a negative effect on cell survival, low/medium concentrations of sFRP1 or sFRP2 promoted the DA differentiation of progenitors derived from primary VM cultures or mouse embryonic stem cells (ESCs), mimicking the effects of Wnt5a. We thus conclude that the main function of sFRP1 and sFRP2 is to enhance Wnt/PCP signaling in DA cells and to regulate Wnt/PCP-dependent functions in midbrain development. Moreover, we suggest that lowmedium concentrations of sFRPs may be used to enhance the DA differentiation of ESCs and improve their therapeutic application. STEM CELLS 2012;30:865875
C1 [Kele, Julianna; Andersson, Emma R.; Villaescusa, J. Carlos; Cajanek, Lukas; Bonilla, Sonia; Toledo, Enrique M.; Bryja, Vitezslav; Arenas, Ernest] Karolinska Inst, Lab Mol Neurobiol Med Biochem & Biophys, S-17177 Stockholm, Sweden.
[Parish, Clare L.] Univ Melbourne, Florey Neurosci Inst, Parkville, Vic 3052, Australia.
[Parish, Clare L.] Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia.
[Rubin, Jeffrey S.] NCI CCR LCMB, MSC 4255, Bethesda, MD USA.
[Shimono, Akihiko] Natl Univ Singapore, Ctr Life Sci 02 07, Canc Sci Inst Singapore, Singapore, Singapore.
RP Arenas, E (reprint author), Karolinska Inst, Lab Mol Neurobiol Med Biochem & Biophys, Scheelevag 1, S-17177 Stockholm, Sweden.
EM Ernest.Arenas@ki.se
RI Parish, Clare/A-3380-2014; Toledo, Enrique/E-8860-2010; Bryja,
Vit?zslav/H-1925-2014; Andersson, Emma/J-4236-2012
OI Villaescusa, J. Carlos/0000-0001-9456-9828; Cajanek,
Lukas/0000-0003-2914-8589; Arenas, Ernest/0000-0003-0197-6577; Toledo,
Enrique/0000-0002-1460-4708; Bryja, Vit?zslav/0000-0002-9136-5085;
Andersson, Emma/0000-0002-8608-625X
FU Swedish Research Council (DBRM) [VR2008:2811, 3287]; European Union;
Swedish Foundation for Strategic Research (INGVAR and DBRM); Norwegian
Research Council; Karolinska Institute; National Health and Medical
Research Council (NHMRC), Australia; Swedish National Neuroscience
Network; FEBS; EMBO; Ministry of Education, Youth and Sports of the
Czech Republic [MSM0021622430]; NHMRC
FX We thank Carmen Ramirez-Castillejo, Helena Mira, and Carmen Salto, for
support and assistance; Alessandra Nanni for secretarial help; Johan
Glad for help with statistical analysis; Johnny Soderlund and Lottie
Jansson-Sjostrand for additional assistance. This work was supported by
grants from the Swedish Research Council (DBRM, VR2008:2811 and 3287),
European Union (Neurostemcell and Eurostemcell), Swedish Foundation for
Strategic Research (INGVAR and DBRM), Norwegian Research Council, and
Karolinska Institute, National Health and Medical Research Council
(NHMRC), Australia. J.K. was supported by the Swedish National
Neuroscience Network. J.C.V. was supported by a FEBS Long-Term
Fellowship. V. B. was supported by EMBO Installation Grant and Ministry
of Education, Youth and Sports of the Czech Republic (MSM0021622430).
C.L.P was supported by an NHMRC Career development Fellowship,
Australia. J.K. is currently affiliated with Ludwig Institute for Cancer
Research Ltd., Stockholm, Sweden; E.R.A. is currently affiliated with
Department of Cellular and Molecular Biology, Karolinska Institute,
Stockholm, Sweden; S.B. is currently affiliated with Instituto de
Biomedicina de Sevilla, Hospital Virgen del Rocio, Sevilla, Spain; V.B.
is currently affiliated with Institute of Experimental Biology, Faculty
of Science, Masaryk University, Brno, Czech Republic, and Institute of
Biophysics, Brno, Czech Republic.
NR 56
TC 23
Z9 24
U1 0
U2 11
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 MAY
PY 2012
VL 30
IS 5
BP 865
EP 875
DI 10.1002/stem.1049
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 923KD
UT WOS:000302617300008
PM 22290867
ER
PT J
AU Zheng, XF
Dumitru, R
Lackford, BL
Freudenberg, JM
Singh, AP
Archer, TK
Jothi, R
Hu, G
AF Zheng, Xiaofeng
Dumitru, Raluca
Lackford, Brad L.
Freudenberg, Johannes M.
Singh, Ajeet P.
Archer, Trevor K.
Jothi, Raja
Hu, Guang
TI Cnot1, Cnot2, and Cnot3 Maintain Mouse and Human ESC Identity and
Inhibit Extraembryonic Differentiation
SO STEM CELLS
LA English
DT Article
DE Ccr4-Not; Embryonic stem cell; Self-renewal; Pluripotency;
Extraembryonic differentiation
ID EMBRYONIC STEM-CELLS; MESSENGER-RNA METABOLISM; SELF-RENEWAL; CCR4-NOT
COMPLEX; TRANSCRIPTIONAL NETWORK; REGULATORY NETWORKS; SIGNALING
PATHWAYS; PLURIPOTENCY; SCREEN; BIOLOGY
AB Embryonic stem cell (ESC) identity and self-renewal is maintained by extrinsic signaling pathways and intrinsic gene regulatory networks. Here, we show that three members of the Ccr4-Not complex, Cnot1, Cnot2, and Cnot3, play critical roles in maintaining mouse and human ESC identity as a protein complex and inhibit differentiation into the extraembryonic lineages. Enriched in the inner cell mass of blastocysts, these Cnot genes are highly expressed in ESC and downregulated during differentiation. In mouse ESCs, Cnot1, Cnot2, and Cnot3 are important for maintenance in both normal conditions and the 2i/LIF medium that supports the ground state pluripotency. Genetic analysis indicated that they do not act through known self-renewal pathways or core transcription factors. Instead, they repress the expression of early trophectoderm (TE) transcription factors such as Cdx2. Importantly, these Cnot genes are also necessary for the maintenance of human ESCs, and silencing them mainly lead to TE and primitive endoderm differentiation. Together, our results indicate that Cnot1, Cnot2, and Cnot3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in mouse and human ESCs. STEM CELLS 2012;30:910922
C1 [Zheng, Xiaofeng; Dumitru, Raluca; Lackford, Brad L.; Singh, Ajeet P.; Archer, Trevor K.; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Freudenberg, Johannes M.; Jothi, Raja] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Hu, G (reprint author), NIEHS, Mol Carcinogenesis Lab, Bldg 101,Rm D-416,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM hug4@niehs.nih.gov
RI Singh, Ajeet/G-3935-2013; Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016
OI Hu, Guang/0000-0003-0437-4723
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01ES102745, Z01ES071006-11, 1ZIAES102625-02]
FX We thank Drs. Thomas Kunkel, Paul Wade, Carmen Williams (NIEHS), Rene
Maehr (UMass Med), and Guokai Chen (NHLBI) for providing insightful
comments and suggestions on the manuscript. We thank Dr. Austin Smith
for providing the Oct4GiP cells, Dr. Hitoshi Niwa for providing the
Cdx2-/- ESCs, Dr. Janet Rossant for providing the mouse TS
cells, Dr. G. Sebastiaan Winkler (University of Nottingham) and Dr. H.
Th. Marc Timmers (University Medical Centre, Utrecht) for providing the
Cnot1 antibody and technical guidance on detecting the Cnot proteins. We
thank the FACS, microarray, and animal facilities at NIEHS for
assistance with the experiments. This research was supported by the
National Institute of Environmental Health Sciences, National Institutes
of Health Intramural Research Program Z01ES102745 (to G.H.),
Z01ES071006-11 (to T.K.A.), and 1ZIAES102625-02 (to R.J.).
NR 66
TC 24
Z9 34
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD MAY
PY 2012
VL 30
IS 5
BP 910
EP 922
DI 10.1002/stem.1070
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 923KD
UT WOS:000302617300012
PM 22367759
ER
PT J
AU Lee, SB
Seo, D
Choi, D
Park, KY
Holczbauer, A
Marquardt, JU
Conner, EA
Factor, VM
Thorgeirsson, SS
AF Lee, Seung Bum
Seo, Daekwan
Choi, Dongho
Park, Kye-Yoon
Holczbauer, Agnes
Marquardt, Jens U.
Conner, Elizabeth A.
Factor, Valentina M.
Thorgeirsson, Snorri S.
TI Contribution of Hepatic Lineage Stage-Specific Donor Memory to the
Differential Potential of Induced Mouse Pluripotent Stem Cells
SO STEM CELLS
LA English
DT Article
DE Induced pluripotent stem cells; Donor memory; Hepatocyte lineage cells;
Hepatic differentiation
ID LIVER DEVELOPMENT; IPS CELLS; HEPATOCYTE DIFFERENTIATION; EPIGENETIC
MEMORY; GENE-EXPRESSION; DEFINED FACTORS; ONCOSTATIN-M; GENERATION;
SWI/SNF; METHYLATION
AB Recent studies suggested that induced pluripotent stem cells (iPSCs) retain a residual donor cell gene expression, which may impact their capacity to differentiate into cell of origin. Here, we addressed a contribution of a lineage stage-specific donor cell memory in modulating the functional properties of iPSCs. iPSCs were generated from hepatic lineage cells at an early (hepatoblast-derived, HB-iPSCs) and end stage (adult hepatocyte, AH-iPSCs) of hepatocyte differentiation as well as from mouse embryonic fibroblasts (MEFs-iPSCs) using a lentiviral vector encoding four pluripotency-inducing factors Oct4, Sox2, Klf4, and c-Myc. All resulting iPSC lines acquired iPSCs phenotype as judged by the accepted criteria including morphology, expression of pluripotency markers, silencing of transducing factors, capacity of multilineage differentiation in teratoma assay, and normal diploid karyotype. However, HB-iPSCs were more efficient in directed differentiation toward hepatocytic lineage as compared to AH-iPSCs, MEF-iPSCs, or mouse embryonic stem cells (mESCs). Extensive comparative transcriptome analyses of the early passage iPSCs, donor cells, and mESCs revealed that despite global similarities in gene expression patterns between generated iPSCs and mESCs, HB-iPSCs retained a transcriptional memory (seven upregulated and 17 downregulated genes) typical of the original cells. Continuous passaging of HB-iPSCs erased most of these differences including a superior capacity for hepatic redifferentiation. These results suggest that retention of lineage stage-specific donor memory in iPSCs may facilitate differentiation into donor cell type. The identified gene set may help to improve hepatic differentiation for therapeutic applications and contribute to the better understanding of liver development. STEM CELLS 2012;30:9971007
C1 [Lee, Seung Bum; Seo, Daekwan; Choi, Dongho; Holczbauer, Agnes; Marquardt, Jens U.; Conner, Elizabeth A.; Factor, Valentina M.; Thorgeirsson, Snorri S.] Natl Canc Inst, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Park, Kye-Yoon] Natl Inst Neurol Disorders & Stroke, Stem Cell Unit, NIH, Bethesda, MD 20892 USA.
[Choi, Dongho] Soonchunhyang Univ, Coll Med, Dept Surg, Seoul, South Korea.
RP Thorgeirsson, SS (reprint author), Natl Canc Inst, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4146, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
FU US National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Susan Garfiled and Langston Lim for the assistance with
confocal imaging and Barbara Taylor for the help with
fluorescence-activated cell sorting analysis. This research was
supported by the Intramural Research Program of the US National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 55
TC 29
Z9 29
U1 0
U2 6
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 MAY
PY 2012
VL 30
IS 5
BP 997
EP 1007
DI 10.1002/stem.1074
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 923KD
UT WOS:000302617300020
PM 22378611
ER
PT J
AU Masedunskas, A
Porat-Shliom, N
Weigert, R
AF Masedunskas, Andrius
Porat-Shliom, Natalie
Weigert, Roberto
TI Regulated Exocytosis: Novel Insights from Intravital Microscopy
SO TRAFFIC
LA English
DT Review
DE actin; cytoskeleton; exocrine secretion; in vivo imaging; intravital
microscopy; light microscopy; regulated exocytosis
ID REFLECTION FLUORESCENCE MICROSCOPY; ACINAR EPITHELIAL-CELLS; RAT
SUBMANDIBULAR-GLAND; FUSION PORE; 2-PHOTON MICROSCOPY; COMPOUND
EXOCYTOSIS; SECRETORY GRANULES; MULTIPHOTON MICROSCOPY; DIRECT
VISUALIZATION; VESICLE EXOCYTOSIS
AB Regulated exocytosis is a fundamental process that every secretory cell uses to deliver molecules to the cell surface and the extracellular space by virtue of membranous carriers. This process has been extensively studied using various approaches such as biochemistry, electrophysiology and electron microscopy. However, recent developments in time-lapse light microscopy have made possible imaging individual exocytic events, hence, advancing our understanding of this process at a molecular level. In this review, we focus on intravital microscopy (IVM), a light microscopy-based approach that enables imaging subcellular structures in live animals, and discuss its recent application to study regulated exocytosis. IVM has revealed differences in regulation and modality of regulated exocytosis between in vitro and in vivo model systems, unraveled novel aspects of this process that can be appreciated only in in vivo settings and provided valuable and novel information on its molecular machinery. In conclusion, we make the case for IVM being a mature technique that can be used to investigate the molecular machinery of several intracellular events under physiological conditions.
C1 [Masedunskas, Andrius; Porat-Shliom, Natalie; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Masedunskas, Andrius] Univ N Carolina, Dept Biol, Chapel Hill, NC 27514 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr 303A, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU NIH, National Institute of Dental and Craniofacial Research (NIDCR)
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research (NIDCR). We
apologize to those whose work could not be cited because of space
limitations.
NR 69
TC 12
Z9 12
U1 3
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD MAY
PY 2012
VL 13
IS 5
BP 627
EP 634
DI 10.1111/j.1600-0854.2012.01328.x
PG 8
WC Cell Biology
SC Cell Biology
GA 923LR
UT WOS:000302621300001
PM 22243493
ER
PT J
AU Lazny, R
Wolosewicz, K
Dauter, Z
Brzezinski, K
AF Lazny, Ryszard
Wolosewicz, Karol
Dauter, Zbigniew
Brzezinski, Krzysztof
TI (1RS, 2SR,
5SR)-9-Benzyl-2-[(1RS)-1-hydroxybenzyl]-9-azabicyclo[3.3.1]nonan-3-one
from synchrotron data
SO ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS
LA English
DT Article
AB In the crystal structure of the racemic title compound, C22H25NO2, solved and refined against sychrotron diffraction data, the hydroxy group and the carbonyl O atom participate in the formation of O-H center dot center dot center dot O hydrogen bonds between pairs of enantiomers related by a crystallographic centre of symmetry.
C1 [Lazny, Ryszard; Wolosewicz, Karol; Brzezinski, Krzysztof] Univ Bialystok, Inst Chem, Hurtowa 1, PL-15399 Bialystok, Poland.
[Dauter, Zbigniew; Brzezinski, Krzysztof] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA.
RP Lazny, R (reprint author), Univ Bialystok, Inst Chem, Hurtowa 1, PL-15399 Bialystok, Poland.
EM lazny@uwb.edu.pl
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]
NR 12
TC 5
Z9 5
U1 0
U2 6
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2056-9890
J9 ACTA CRYSTALLOGR E
JI Acta Crystallogr. Sect. E.-Crystallogr. Commun.
PD MAY
PY 2012
VL 68
BP O1367
EP +
DI 10.1107/S1600536812014754
PN 5
PG 8
WC Crystallography
SC Crystallography
GA V46AT
UT WOS:000209857800216
PM 22590261
ER
PT J
AU Lieberman, AP
Puertollano, R
Raben, N
Slaugenhaupt, S
Walkley, SU
Ballabio, A
AF Lieberman, Andrew P.
Puertollano, Rosa
Raben, Nina
Slaugenhaupt, Susan
Walkley, Steven U.
Ballabio, Andrea
TI Autophagy in lysosomal storage disorders
SO AUTOPHAGY
LA English
DT Review
DE autophagy; glycogenosis; Mucolipidosis Type IV; lysosomal storage
disorders; mucopolysaccharidoses; lysosomes; sphingolipidoses
ID MUCOLIPIDOSIS TYPE-IV; MULTIPLE SULFATASE DEFICIENCY; PICK-C DISEASE;
PHOSPHOTRANSFERASE ALPHA/BETA-SUBUNITS; NEURONAL CEROID-LIPOFUSCINOSIS;
ENZYME REPLACEMENT THERAPY; SINGLE MUSCLE-FIBERS; POMPE-DISEASE; MOUSE
MODEL; GAUCHER-DISEASE
AB Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as "autophagy disorders."
C1 [Ballabio, Andrea] Telethon Inst Genet & Med TIGEM, Naples, Italy.
[Ballabio, Andrea] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
[Ballabio, Andrea] Univ Naples Federico II, Dept Pediat, Naples, Italy.
[Lieberman, Andrew P.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Puertollano, Rosa; Raben, Nina] NIH, Bethesda, MD 20892 USA.
[Puertollano, Rosa] NHLBI, Cell Biol Lab, Bethesda, MD USA.
[Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, Bethesda, MD USA.
[Slaugenhaupt, Susan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Walkley, Steven U.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA.
RP Ballabio, A (reprint author), Telethon Inst Genet & Med TIGEM, Naples, Italy.
EM ballabio@tigem.it
OI BALLABIO, Andrea/0000-0003-1381-4604
FU NIH [R01 NS063967, HD045561]; NIH, National Heart, Lung, and Blood
Institute (NHLBI); Beyond Batten Disease Foundation; Telethon
Foundation; European Research Council (ERC) [250154]
FX We thank Dr. G. Diez-Roux for manuscript preparation, helpful
discussions and critical reading of the manuscript and C. Settembre for
critical reading of the manuscript. A. P. L. is supported by the NIH
grant R01 NS063967; R. P. is supported by the Intramural Research
Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI);
S. U. W. is supported by NIH grant HD045561; A. B. is supported by the
Beyond Batten Disease Foundation, the Telethon Foundation and the
European Research Council (ERC) grant #250154.
NR 132
TC 115
Z9 119
U1 3
U2 21
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD MAY
PY 2012
VL 8
IS 5
BP 719
EP 730
DI 10.4161/auto.19469
PG 12
WC Cell Biology
SC Cell Biology
GA 960QU
UT WOS:000305403800002
PM 22647656
ER
PT J
AU Codispoti, KET
Beason-Held, LL
Kraut, MA
O'Brien, RJ
Rudow, G
Pletnikova, O
Crain, B
Troncoso, JC
Resnick, SM
AF Codispoti, Kari-Elise T.
Beason-Held, Lori L.
Kraut, Michael A.
O'Brien, Richard J.
Rudow, Gay
Pletnikova, Olga
Crain, Barbara
Troncoso, Juan C.
Resnick, Susan M.
TI Longitudinal brain activity changes in asymptomatic Alzheimer disease
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE Amyloid; dementia; fMRI; neuropathology; PET; resting state; tau
AB Asymptomatic Alzheimer disease (ASYMAD) is characterized by normal cognition despite substantial AD pathology. To identify factors contributing to cognitive resilience, we compared early changes in regional cerebral blood flow (rCBF) in individuals subsequently diagnosed as ASYMAD with changes in cognitively impaired (CI) and normal older participants from the Baltimore Longitudinal Study of Aging. Participants underwent annual positron emission tomography (PET) rCBF measurements beginning 10.0 (SD 3.6) years before death and while cognitively intact. Based on clinical and autopsy information, subjects were grouped as cognitively normal (CN = 7), ASYMAD (n = 6), and CI (= 6). Autopsy material was analyzed using CERAD and Braak scores and quantitative stereologic measures of tau and amyloid. ASYMAD and CI groups had similar CERAD and Braak scores, similar amounts of beta-amyloid and tau in middle frontal (MFG), middle temporal (MTG), and inferior parietal (IP) regions, and more beta-amyloid than CN in precuneus, MFG, and IP areas. Voxel-based PET analysis identified similarities and differences in longitudinal rCBF change among groups across a 7.2-year interval. Both ASYMAD and CI groups showed similar longitudinal rCBF declines in precuneus, lingual, and MTG regions relative to CN. The CI also showed greater rCBF decreases in anterior and posterior cingulate, cuneus, and brainstem regions relative to ASYMAD and CN, whereas ASYMAD showed greater relative rCBF increases over time in medial temporal and thalamic regions relative to CI and CN. Our findings provide evidence of early functional alterations that may contribute to cognitive resilience in those who accumulate AD pathology but maintain normal cognition.
C1 [Codispoti, Kari-Elise T.; Rudow, Gay; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan C.] Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
[Beason-Held, Lori L.] NIA, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA.
[Kraut, Michael A.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21205 USA.
[O'Brien, Richard J.; Troncoso, Juan C.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
RP Codispoti, KET (reprint author), Johns Hopkins Univ, Dept Pathol, Div Neuropathol, 720 Rutland Ave,558 Ross Res Bldg, Baltimore, MD 21205 USA.
EM kcodisp1@jhmi.edu
FU Intramural Research Program of the NIH, National Institute on Aging;
Johns Hopkins Alzheimer Disease Research Center [P50AG05146];
Alzheimer's Association [IIRG-09134090]; Ruth L. Kirschstein National
Research Service Award [T32EB006351-05]; Research and Development
[N01-AG-3-2124]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging, the Johns Hopkins Alzheimer
Disease Research Center (P50AG05146), the Alzheimer's Association
(IIRG-09134090), the Ruth L. Kirschstein National Research Service Award
(T32EB006351-05), and by Research and Development Contract
N01-AG-3-2124. We are grateful to the BLSA participants and staff for
their dedication to these studies, the staff of the Johns Hopkins PET
facility for their assistance, and to Dr. Mony de Leon for his
thoughtful review of the manuscript.
NR 36
TC 6
Z9 6
U1 1
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD MAY
PY 2012
VL 2
IS 3
BP 221
EP 230
DI 10.1002/brb3.47
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V35UR
UT WOS:000209174000003
PM 22741095
ER
PT J
AU Bekker, LG
Beyrer, C
Quinn, TC
AF Bekker, Linda-Gail
Beyrer, Chris
Quinn, Thomas C.
TI Behavioral and Biomedical Combination Strategies for HIV Prevention
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; SUB-SAHARAN AFRICA; ACTIVE
ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED
CONTROLLED-TRIAL; FEMALE SEX WORKERS; HOMOSEXUAL BISEXUAL MEN;
HERPES-SIMPLEX-VIRUS; MALE CIRCUMCISION; HETEROSEXUAL TRANSMISSION
AB Around 2.5 million people become infected with HIV each year. This extraordinary toll on human life and public health worldwide will only be reversed with effective prevention. What's more, in the next few years, it is likely at least, that no single prevention strategy will be sufficient to contain the spread of the disease. There is a need for combination prevention as there is for combination treatment, including biomedical, behavioral, and structural interventions. Expanded HIV prevention must be grounded in a systematic analysis of the epidemic's dynamics in local contexts. Although 85% of HIV is transmitted sexually, effective combinations of prevention have been shown for people who inject drugs. Combination prevention should be based on scientifically derived evidence, with input and engagement from local communities that fosters the successful integration of care and treatment.
C1 [Bekker, Linda-Gail] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Beyrer, Chris] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Sect Int HIV STD Res, NIH, Bethesda, MD 20892 USA.
RP Bekker, LG (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
EM Linda-gail.bekker@hiv-research.org.za
NR 146
TC 0
Z9 0
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 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD MAY
PY 2012
VL 4
IS 5
AR a007435
DI 10.1101/cshperspect.a007435
PG 23
WC Cell Biology
SC Cell Biology
GA 995PV
UT WOS:000308024100007
ER
PT J
AU Ribeiro-Gomes, FL
Sacks, D
AF Ribeiro-Gomes, Flavia L.
Sacks, David
TI The influence of early neutrophil-Leishmania interactions on the host
immune response to infection
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Review
DE neutrophils; Leishmania; inflammation; immune response; sand fly;
apoptosis; dendritic cells; macrophages
ID MAJOR INFECTION; CUTANEOUS LEISHMANIASIS; POLYMORPHONUCLEAR LEUKOCYTES;
DONOVANI PROMASTIGOTES; EXTRACELLULAR TRAPS; MONOCLONAL-ANTIBODY;
SUSCEPTIBLE MICE; PARASITE BURDEN; LYMPH-NODES; IN-VIVO
AB Neutrophils are the first cells recruited to the dermal site of Leishrnania infection following injection by needle or sand fly bite. The role of neutrophils in either promoting or suppressing host immunity remains controversial. We discuss the events driving neutrophil recruitment, their interaction with the parasite and apoptotic fate, and the nature of their encounters with other innate cells. We suggest that the influence of the neutrophil response on infection outcome critically depends on the timing of their recruitment and the tissue environment in which it occurs.
C1 [Ribeiro-Gomes, Flavia L.; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
RI Ribeiro-Gomes, Flavia/F-7609-2015
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 59
TC 28
Z9 28
U1 0
U2 4
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD MAY
PY 2012
VL 2
AR UNSP 59
DI 10.3389/fcimb.2012.00059
PG 8
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 220ZU
UT WOS:000324627400005
PM 22919650
ER
PT J
AU Zheng, XF
Hu, G
AF Zheng, Xiaofeng
Hu, Guang
TI Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem
Cell Maintenance and Self-renewal
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Stem Cell Biology; Issue 63; Molecular Biology; Genetics; Embryonic stem
cell; ESC; self-renewal; differentiation; Oct4; GFP; reporter assay;
RNAi
AB Pluripotency and self-renewal are two defining characteristics of embryonic stem cells (ES cells). Understanding the underlying molecular mechanism will greatly facilitate the use of ES cells for developmental biology studies, disease modeling, drug discovery, and regenerative medicine (reviewed in(1,2)).
To expedite the identification and characterization of novel regulators of ES cell maintenance and self-renewal, we developed a fluorescence reporter-based assay to quantitatively measure the self-renewal status in mouse ES cells using the Oct4GiP cells(3). The Oct4GiP cells express the green fluorescent protein (GFP) under the control of the Oct4 gene promoter region(4,5). Oct4 is required for ES cell self-renewal, and is highly expressed in ES cells and quickly down-regulated during differentiation(6,7). As a result, GFP expression and fluorescence in the reporter cells correlates faithfully with the ES cell identity(5), and fluorescence-activated cell sorting (FACS) analysis can be used to closely monitor the self-renewal status of the cells at the single cell level(3,8).
Coupled with RNAi, the Oct4GiP reporter assay can be used to quickly identify and study regulators of ES cell maintenance and self-renewal(3,8). Compared to other methods for assaying self-renewal, it is more convenient, sensitive, quantitative, and of lower cost. It can be carried out in 96-or 384-well plates for large-scale studies such as high-throughput screens or genetic epistasis analysis. Finally, by using other lineage-specific reporter ES cell lines, the assay we describe here can also be modified to study fate specification during ES cell differentiation.
C1 [Zheng, Xiaofeng; Hu, Guang] Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
RP Hu, G (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
EM hug4@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health Intramural Research Program [Z01ES102745]
FX We thank Brad Lackford for reading and editing the manuscript. This
research was supported by the National Institute of Environmental Health
Sciences, National Institutes of Health Intramural Research Program
Z01ES102745 (to G. H.).
NR 19
TC 0
Z9 0
U1 0
U2 1
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAY
PY 2012
IS 63
AR UNSP e3987
DI 10.3791/3987
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PH
UT WOS:000209223000043
ER
PT J
AU Campos, NG
Castle, PE
Schiffman, M
Kim, JJ
AF Campos, Nicole G.
Castle, Philip E.
Schiffman, Mark
Kim, Jane J.
TI Policy Implications of Adjusting Randomized Trial Data for Economic
Evaluations: A Demonstration from the ASCUS-LSIL Triage Study
SO MEDICAL DECISION MAKING
LA English
DT Article
DE economic evaluation; randomized trial; bias; cervical cancer; human
papillomavirus
ID ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL LESION TRIAGE; UNDETERMINED
SIGNIFICANCE; HUMAN-PAPILLOMAVIRUS; COST-EFFECTIVENESS; CERVICAL
CYTOLOGY; RESEARCH DESIGNS; STRATEGIES; MANAGEMENT; ALTS
AB Background. Although the randomized controlled trial (RCT) is widely considered the most reliable method for evaluation of health care interventions, challenges to both internal and external validity exist. Thus, the efficacy of an intervention in a trial setting does not necessarily represent the real-world performance that decision makers seek to inform comparative effectiveness studies and economic evaluations. Methods. Using data from the ASCUS-LSIL Triage Study (ALTS), we performed a simplified economic evaluation of age-based management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) among women who were referred to the study with low-grade squamous intraepithelial lesions (LSIL). We used data from the trial itself to adjust for 1) potential lead time bias and random error that led to variation in the observed prevalence of CIN3 by study arm and 2) potential ascertainment bias among providers in the most aggressive management arm. Results. We found that using unadjusted RCT data may result in counterintuitive cost-effectiveness results when random error and/or bias are present. Following adjustment, the rank order of management strategies changed for 2 of the 3 age groups we considered. Conclusions. Decision analysts need to examine study design, available trial data, and cost-effectiveness results closely in order to detect evidence of potential bias. Adjustment for random error and bias in RCTs may yield different policy conclusions relative to unadjusted trial data.
C1 [Campos, Nicole G.; Kim, Jane J.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
[Campos, Nicole G.] Univ Miami, Ctr Excellence Hlth Dispar Res El Ctr, Sch Nursing & Hlth Studies, Coral Gables, FL 33124 USA.
[Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC USA.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Campos, NG (reprint author), POB 248153, Coral Gables, FL 33124 USA.
EM gastin@post.harvard.edu
FU National Cancer Institute [R01 CA93435]; National Institutes of
Health/National Cancer Institute; National Cancer Institute, National
Institutes of Health, Department of Health and Human Services [CN-55153,
CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55105]
FX Received 5 November 2010 from the Center for Health Decision Science,
Harvard School of Public Health, Boston, MA (NGC, JJK); Center of
Excellence for Health Disparities Research-El Centro, School of Nursing
and Health Studies, University of Miami, Coral Gables, FL (NGC);
American Society for Clinical Pathology Institute, Washington, DC (PEC);
and Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, Rockville, MD (MS). This work
was supported by the National Cancer Institute (R01 CA93435), the
National Institutes of Health/National Cancer Institute Intramural
Research Program, and the National Cancer Institute, National Institutes
of Health, Department of Health and Human Services (contract no.
CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159,
and CN-55105). PEC has received donations of HPV tests from Qiagen and
serves on a data safety and monitoring committee for Merck, the
manufacturer of Gardasil, for which he receives compensation. Revision
accepted for publication 31 August 2011.
NR 36
TC 4
Z9 4
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD MAY-JUN
PY 2012
VL 32
IS 3
BP 400
EP 427
DI 10.1177/0272989X11428516
PG 28
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 951ET
UT WOS:000304704300005
PM 22147881
ER
PT J
AU Fang, F
Umbach, DM
Xu, ZL
Ye, WM
Sandler, DP
Taylor, JA
Kamel, F
AF Fang, Fang
Umbach, David M.
Xu, Zongli
Ye, Weimin
Sandler, Dale P.
Taylor, Jack A.
Kamel, Freya
TI No association between DNA repair gene XRCC1 and amyotrophic lateral
sclerosis
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; DNA repair; XRCC1
ID POPULATION
AB Reduced DNA repair capacity may play a role in amyotrophic lateral sclerosis (ALS) etiology. We examined the association between ALS risk and single nucleotide polymorphisms (SNPs) in the gene x-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) utilizing data from a case-control study and 2 genome-wide association studies the study of Irish Amyotrophic Lateral Sclerosis and the National Institute of Neurological Disorders and Stroke (NINDS,) genome-wide study in Amyotrophic Lateral Sclerosis and Neurologically Normal Controls). Our results did not show any differences in the frequency of XRCC1 gene polymorphisms between ALS patients and controls free of any neurological disease. Published by Elsevier Inc.
C1 [Fang, Fang; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Fang, Fang; Xu, Zongli; Sandler, Dale P.; Taylor, Jack A.; Kamel, Freya] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Fang, F (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, S-17177 Stockholm, Sweden.
EM fang.fang@ki.se
OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615; xu,
zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398; Sandler,
Dale/0000-0002-6776-0018
FU NIH, National Institute of Environmental Health Sciences [Z01
ES49005-15]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (Z01
ES49005-15).
NR 5
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2012
VL 33
IS 5
AR 1015.e25
DI 10.1016/j.neurobiolaging.2010.07.004
PG 2
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 921OF
UT WOS:000302486200049
PM 20719408
ER
PT J
AU Huey, ED
Ferrari, R
Moreno, JH
Jensen, C
Morris, CM
Potocnik, F
Kalaria, RN
Tierney, M
Wassermann, EM
Hardy, J
Grafman, J
Momeni, P
AF Huey, Edward D.
Ferrari, Raffaele
Moreno, Jorge H.
Jensen, Christopher
Morris, Christopher M.
Potocnik, Felix
Kalaria, Rajesh N.
Tierney, Michael
Wassermann, Eric M.
Hardy, John
Grafman, Jordan
Momeni, Parastoo
TI FUS and TDP43 genetic variability in FTD and CBS
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Frontotemporal dementia; Corticobasal syndrome; Genetics; FUS; TDP-43
ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; TARDBP
MUTATIONS; TDP-43; DEMENTIA; DISEASE
AB This study aimed to evaluate genetic variability in the FUS and TDP-43 genes, known to be mainly associated with amyotrophic lateral sclerosis (ALS), in patients with the diagnoses of frontotemporal lobar degeneration (FTLD) and corticobasal syndrome (CBS). We screened the DNA of 228 patients for all the exons and flanking introns of FUS and TDP-43 genes. We identified 2 novel heterozygous missense mutations in FUS: P106L (g.22508384C>T) in a patient with behavioral variant frontotemporal dementia (bvFTD) and Q179H in several members of a family with behavioral variant FTD. We also identified the N267S mutation in TDP-43 in a CBS patient, previously only reported in 1 ALS family and 1 FTD patient. Additionally, we identified 2 previously reported heterozygous insertion and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180-4185 delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185-4186 insGAGGTG) in a patient with diagnosis of CBS. Not least, we have found a series of variants in FUS also in neurologically normal controls. In summary, we report that genetic variability in FUS and TDP-43 encompasses a wide range of phenotypes (including ALS, FTD, and CBS) and that there is substantial genetic variability in FUS gene in neurologically normal controls. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ferrari, Raffaele; Moreno, Jorge H.; Jensen, Christopher; Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA.
[Huey, Edward D.] Columbia Univ, Med Ctr, Taub Inst, New York, NY USA.
[Huey, Edward D.] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA.
[Huey, Edward D.; Tierney, Michael; Wassermann, Eric M.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Ferrari, Raffaele; Hardy, John] UCL, Inst Neurol, London, England.
[Morris, Christopher M.; Kalaria, Rajesh N.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Potocnik, Felix] Univ Stellenbosch, Dept Psychiat, Cape Town, South Africa.
[Hardy, John] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Grafman, Jordan] Kessler Fdn, Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ USA.
RP Momeni, P (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, 4C101-4C160-4C127,3601 4th St,STOP 9410, Lubbock, TX 79430 USA.
EM parastoo.momeni@ttuhsc.edu
RI Hardy, John/C-2451-2009;
OI Grafman, Jordan H./0000-0001-8645-4457
FU office of the Dean of the School of Medicine, Department of Internal
Medicine, at Texas Tech Health Sciences Center; South Plains Foundation;
NIH NINDS [5R00NS060766]; NINDS
FX Molecular genetics work was funded by the office of the Dean of the
School of Medicine, Department of Internal Medicine, at Texas Tech
Health Sciences Center and a grant from South Plains Foundation (PM).
This work was also supported by NIH NINDS grant 5R00NS060766 (EDH), and
the NINDS Intramural Research Program (JG). The authors thank Cynthia
Crews, Anne Leopold, and Karen DeTucci for the study coordination, Dr
Susan Bergeson for sharing her control DNA samples with PM for genetic
screening, Poorna Dharmasri for proofreading of the manuscript, and
Stephanie Cosentino for comments.
NR 26
TC 8
Z9 8
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2012
VL 33
IS 5
AR 1016.e9
DI 10.1016/j.neurobiolaging.2011.08.004
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 921OF
UT WOS:000302486200051
PM 21943958
ER
PT J
AU Takekoshi, T
Fang, L
Paragh, G
Hwang, ST
AF Takekoshi, T.
Fang, L.
Paragh, G.
Hwang, S. T.
TI CCR7-expressing B16 melanoma cells downregulate
interferon-gamma-mediated inflammation and increase lymphangiogenesis in
the tumor microenvironment
SO ONCOGENESIS
LA English
DT Article
DE melanoma; CCR7; IFN-gamma; lymphangiogenesis
AB The expression of the CC chemokine receptor-7 (CCR7) by cancers, including melanoma, augments lymph node (LN) metastasis, but little is known about its role in lymphangiogenesis and anti-tumor immunity. We injected control B16 murine melanoma cells (pLNCX2-B16) and CCR7-overexpressing B16 cells (CCR7-B16) in murine footpads and compared resulting tumors at the protein and mRNA level using immunostaining, Affymetrix gene microarray and quantitative reverse-transcriptase PCR. Although control and CCR7-B16 primary tumors were of similar size, LN metastasis was dramatically enhanced in CCR7-B16 tumors. Microarray analysis of leukocyte-depleted pLNCX2-B16 and CCR7-B16 tumor cell suspensions showed that three major groups of genes linked to interferon (IFN)-gamma signaling pathways (for example, STAT1, CXCR 9-11, CCL5 and CXCL10, major histocompatibility complex (MHC) I and MHC II) were downregulated in the CCR7-B16 tumor microenvironment, suggesting activation through CCR7 can downregulate pathways critical for host anti-tumor immunity. In addition, mRNA expression of the lymphatic marker podoplanin was upregulated in CCR7-B16 tumors by 3.35-fold versus control tumors. Anti-podoplanin monoclonal antibody staining revealed a three-fold increase in intratumoral CCL21-expressing lymphatic vessels, as well as a two-fold increase in the number of invading tumor cells per lymphatic vessel in CCR7-B16 versus control tumors. Enhanced anti-vascular endothelial growth factor C (VEGF-C) staining was present in CCR7-B16 versus control tumors, suggesting that VEGF-C may have a role in the CCR7-mediated lymphangiogenesis. In summary, CCR7-B16 tumors show a striking decrease in IFN-gamma-mediated inflammatory gene expression in contrast to increased expression of VEGF-C, CCL21 and podoplanin by lymphatic vessels. Enhanced lymphangiogenesis may contribute to the dramatic increase in LN metastasis that is observed in the CCR7-expressing tumors.
C1 [Takekoshi, T.; Paragh, G.; Hwang, S. T.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA.
[Takekoshi, T.; Paragh, G.; Hwang, S. T.] Froedtert Hosp, Milwaukee, WI 53226 USA.
[Fang, L.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
RP Hwang, ST (reprint author), Med Coll Wisconsin, Dept Dermatol, FEC 4100,9200W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM sthwang@mcw.edu
FU Advancing Healthier Wisconsin Research Funds; Advancing Healthier
Wisconsin Endowment of the Medical College of Wisconsin; Ann's Hope
Foundation for Melanoma; MCW/Froedtert Cancer Center Collaborative
Research Fellowship; Intramural Research Program of the National Cancer
Institute
FX We thank Dr Ryan E Sells, Dr Xuesong Wu, Mr Nathan Duncan and Dr
Tomotaka Mabuchi (Department of Dermatology, MCW) for their advice and
technical support. This study was supported by the Advancing Healthier
Wisconsin Research Funds, Advancing Healthier Wisconsin Endowment of the
Medical College of Wisconsin and The Ann's Hope Foundation for Melanoma
(to STH), an MCW/Froedtert Cancer Center Collaborative Research
Fellowship (to TT) and the Intramural Research Program of the National
Cancer Institute (STH and LF).
NR 24
TC 5
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD MAY
PY 2012
VL 1
AR UNSP e9
DI 10.1038/oncsis.2012.9
PG 9
WC Oncology
SC Oncology
GA V36NR
UT WOS:000209219000001
PM 23552640
ER
PT J
AU Malachowa, N
Kobayashi, SD
DeLeo, FR
AF Malachowa, Natalia
Kobayashi, Scott D.
DeLeo, Frank R.
TI Community-Associated Methicillin-Resistant Staphylococcus aureus and
Athletes
SO PHYSICIAN AND SPORTSMEDICINE
LA English
DT Article
DE antibiotics; CA-MRSA; hygiene; infection; innate immunity; MRSA;
resistance; Staphylococcus aureus
ID SOFT-TISSUE INFECTIONS; PANTON-VALENTINE LEUKOCIDIN; CASSETTE CHROMOSOME
MEC; INDUCIBLE CLINDAMYCIN RESISTANCE; MUPIROCIN RESISTANCE; VIRULENCE
DETERMINANTS; ALPHA-TOXIN; CUTANEOUS INFECTIONS; NASAL COLONIZATION;
DISK DIFFUSION
AB The remarkable ability of Staphylococcus aureus to develop antibiotic resistance in conjunction with the emergence of highly virulent and/or transmissible strains has established the pathogen as a leading cause of human bacterial infections worldwide. Historically, methicillin-resistant S aureus (MRSA) was found almost exclusively in hospitals and/or health care-related facilities. However, in the late 1990s, community-associated MRSA strains emerged in the United States and rapidly became the leading cause of community-associated bacterial infections. An enhanced understanding of the pathogenesis and epidemiology of this bacterium is fundamental for the prevention and/or treatment of community-associated MRSA infections. This review highlights salient features of S aureus biology that contribute to the exceptional ability of this pathogen to cause human disease, as well as discusses, in brief, the established approaches for treatment and prevention of infection.
C1 [Malachowa, Natalia; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The authors are supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. We thank Austin Athman (Visual and Medical Arts,
NIAID) for photography assistance.
NR 103
TC 4
Z9 4
U1 1
U2 16
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0091-3847
J9 PHYSICIAN SPORTSMED
JI Physician Sportsmed.
PD MAY
PY 2012
VL 40
IS 2
BP 13
EP 21
DI 10.3810/psm.2012.05.1960
PG 9
WC Primary Health Care; Orthopedics; Sport Sciences
SC General & Internal Medicine; Orthopedics; Sport Sciences
GA 107DU
UT WOS:000316195800001
PM 22759601
ER
PT J
AU Murcia, PR
Hughes, J
Battista, P
Lloyd, L
Baillie, GJ
Ramirez-Gonzalez, RH
Ormond, D
Oliver, K
Elton, D
Mumford, JA
Caccamo, M
Kellam, P
Grenfell, BT
Holmes, EC
Wood, JLN
AF Murcia, Pablo R.
Hughes, Joseph
Battista, Patrizia
Lloyd, Lucy
Baillie, Gregory J.
Ramirez-Gonzalez, Ricardo H.
Ormond, Doug
Oliver, Karen
Elton, Debra
Mumford, Jennifer A.
Caccamo, Mario
Kellam, Paul
Grenfell, Bryan T.
Holmes, Edward C.
Wood, James L. N.
TI Evolution of an Eurasian Avian-like Influenza Virus in Naive and
Vaccinated Pigs
SO PLOS PATHOGENS
LA English
DT Article
ID A VIRUS; HOST-RANGE; HEMAGGLUTININ; SWINE; TRANSMISSION; ORIGIN;
DYNAMICS; SPECIFICITY; PHYLOGENIES; PROGRAM
AB Influenza viruses are characterized by an ability to cross species boundaries and evade host immunity, sometimes with devastating consequences. The 2009 pandemic of H1N1 influenza A virus highlights the importance of pigs in influenza emergence, particularly as intermediate hosts by which avian viruses adapt to mammals before emerging in humans. Although segment reassortment has commonly been associated with influenza emergence, an expanded host-range is also likely to be associated with the accumulation of specific beneficial point mutations. To better understand the mechanisms that shape the genetic diversity of avian-like viruses in pigs, we studied the evolutionary dynamics of an Eurasian Avian-like swine influenza virus (EA-SIV) in naive and vaccinated pigs linked by natural transmission. We analyzed multiple clones of the hemagglutinin 1 (HA1) gene derived from consecutive daily viral populations. Strikingly, we observed both transient and fixed changes in the consensus sequence along the transmission chain. Hence, the mutational spectrum of intra-host EA-SIV populations is highly dynamic and allele fixation can occur with extreme rapidity. In addition, mutations that could potentially alter host-range and antigenicity were transmitted between animals and mixed infections were commonplace, even in vaccinated pigs. Finally, we repeatedly detected distinct stop codons in virus samples from co-housed pigs, suggesting that they persisted within hosts and were transmitted among them. This implies that mutations that reduce viral fitness in one host, but which could lead to fitness benefits in a novel host, can circulate at low frequencies.
C1 [Murcia, Pablo R.; Battista, Patrizia; Mumford, Jennifer A.; Wood, James L. N.] Univ Cambridge, Cambridge Infect Dis Consortium, Dept Vet Med, Cambridge, England.
[Murcia, Pablo R.; Hughes, Joseph] Univ Glasgow, MRC, Coll Med Vet & Life Sci, Ctr Virus Res,Inst Infect Inflammat & Immun, Glasgow, Lanark, Scotland.
[Lloyd, Lucy; Elton, Debra] Ctr Prevent Med, Anim Hlth Trust, Newmarket, Suffolk, England.
[Baillie, Gregory J.; Ormond, Doug; Oliver, Karen; Kellam, Paul] Wellcome Trust Sanger Inst, Cambridge, England.
[Ramirez-Gonzalez, Ricardo H.; Caccamo, Mario] Genome Anal Ctr, Norwich, Norfolk, England.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Murcia, PR (reprint author), Univ Cambridge, Cambridge Infect Dis Consortium, Dept Vet Med, Cambridge, England.
EM jlnw2@cam.ac.uk
RI Wood, James/A-1626-2008; Baillie, Gregory/F-9478-2013; Hughes,
Joseph/B-7711-2009;
OI Wood, James/0000-0002-0258-3188; Holmes, Edward/0000-0001-9596-3552;
Baillie, Gregory/0000-0002-6130-250X; Hughes,
Joseph/0000-0003-2556-2563; Ramirez Gonzalez, Ricardo
Humberto/0000-0001-5745-7085
FU Wellcome Trust; Veterinary Training and Research Initiative; Defra
[VT0105]; Alborada Trust; RAPIDD of the Science & Technology
Directorate, Department of Homeland Security; National Institutes of
Health [R01 GM080533-05]; Fogarty International Center, National
Institutes of Health
FX PRM was supported by the Wellcome Trust. LL and PB were funded by a
Veterinary Training and Research Initiative grant provided through Defra
(VT0105). The sequencing was funded by a programme grant from the
Wellcome Trust. JLNW is supported by the Alborada Trust. BTG and JLNW
were supported by the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. ECH was supported
by grant R01 GM080533-05 from 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 32
TC 29
Z9 29
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2012
VL 8
IS 5
AR e1002730
DI 10.1371/journal.ppat.1002730
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 959OS
UT WOS:000305322900058
PM 22693449
ER
PT J
AU Ferrer, RA
Shmueli, D
Bergman, HE
Harris, PR
Klein, WMP
AF Ferrer, Rebecca A.
Shmueli, Dikla
Bergman, Hannah E.
Harris, Peter R.
Klein, William M. P.
TI Effects of Self-Affirmation on Implementation Intentions and the
Moderating Role of Affect
SO SOCIAL PSYCHOLOGICAL AND PERSONALITY SCIENCE
LA English
DT Article
DE self-affirmation; implementation intentions; positive affect; alcohol;
health behavior change
AB Self-affirmation may offset defensiveness to threatening messages, increase intentions to engage in protective behaviors, and facilitate actual change. Relatively little is known about the conditions under which self-affirmation is most beneficial. The authors examined whether self-affirmation facilitates the forming of implementation intentions-plans to engage in specific steps that facilitate behavior change-and whether effects differ by affective state. Undergraduate female drinkers (N = 265) were self-affirmed or not prior to reading an article linking excessive alcohol consumption to breast cancer susceptibility. They then had the opportunity to report implementation intentions, by listing specific steps they planned to take to reduce consumption. Consistent with predictions, self-affirmation promoted formation of implementation intentions, an effect found only among individuals manifesting positive (as opposed to negative) affect following receipt of the message. Self-affirmation may facilitate behavior change by encouraging development of implementation intentions, an effect that is likely enhanced among those experiencing positive affect.
C1 [Ferrer, Rebecca A.; Shmueli, Dikla; Bergman, Hannah E.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Harris, Peter R.] Univ Sheffield, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England.
RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4083, Rockville, MD 20852 USA.
EM ferrerra@mail.nih.gov
NR 63
TC 12
Z9 13
U1 4
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1948-5506
EI 1948-5514
J9 SOC PSYCHOL PERS SCI
JI Soc. Psychol. Personal Sci.
PD MAY
PY 2012
VL 3
IS 3
BP 300
EP 307
DI 10.1177/1948550611419265
PG 8
WC Psychology, Social
SC Psychology
GA V32FF
UT WOS:000208936400007
ER
PT J
AU Simons-Morton, B
Kuntsche, E
AF Simons-Morton, Bruce
Kuntsche, Emmanuel
TI ADOLESCENT ESTIMATION OF PEER SUBSTANCE USE: WHY IT MATTERS
SO ADDICTION
LA English
DT Editorial Material
DE Drinking; overestimation; peers
ID BEHAVIOR; NORMS
C1 [Simons-Morton, Bruce] NICHHD, Prevent Res Branch, NIH, Bethesda, MD 20892 USA.
[Kuntsche, Emmanuel] Res Inst, Lausanne, Switzerland.
[Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands.
RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, NIH, Bethesda, MD 20892 USA.
EM mortonb@exchange.nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU Intramural NIH HHS [ZIA HD002110-18]
NR 10
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD MAY
PY 2012
VL 107
IS 5
BP 885
EP 886
DI 10.1111/j.1360-0443.2011.03744.x
PG 2
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 919QW
UT WOS:000302344500009
PM 22471569
ER
PT J
AU Evans-Lacko, SE
Baum, N
Danis, M
Biddle, A
Goold, S
AF Evans-Lacko, Sara E.
Baum, Nancy
Danis, Marion
Biddle, Andrea
Goold, Susan
TI Laypersons' Choices and Deliberations for Mental Health Coverage
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES
RESEARCH
LA English
DT Article
DE Mental health; Insurance; Health policy; Consumer preference
ID COMORBIDITY SURVEY REPLICATION; SOCIAL DISTANCE; ILLNESS; CARE;
SERVICES; PARITY; STIGMA; PREFERENCES; RESOURCES; ATTITUDES
AB Insurance coverage for mental health services has historically lagged behind other types of health services. We used a simulation exercise in which groups of laypersons deliberate about healthcare tradeoffs. Groups deciding for their "community" were more likely to select mental health coverage than individuals. Individual prioritization of mental health coverage, however, increased after group discussion. Participants discussed: value, cost and perceived need for mental health coverage, moral hazard and community benefit. A deliberative exercise in priority-setting led a significant proportion of persons to reconsider decisions about coverage for mental health services. Deliberations illustrated public-spiritedness, stigma and significant polarity of views.
C1 [Evans-Lacko, Sara E.] Kings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, London SE5 8AF, England.
[Baum, Nancy; Goold, Susan] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA.
[Danis, Marion] NIH, Sect Eth & Hlth Policy, Dept Clin Bioeth, Bethesda, MD 20892 USA.
[Danis, Marion] NIH, Bioeth Consultat Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Biddle, Andrea] Univ N Carolina, Chapel Hill, NC USA.
[Goold, Susan] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Goold, Susan] Univ Michigan, Bioeth Program, Ann Arbor, MI 48109 USA.
RP Evans-Lacko, SE (reprint author), Kings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, De Crespigny Pk, London SE5 8AF, England.
EM Sara.Evans-Lacko@iop.kcl.ac.uk
RI Evans-Lacko, Sara/A-8768-2011; Evans-Lacko, Sara/F-8489-2014;
OI Evans-Lacko, Sara/0000-0003-4691-2630; Evans-Lacko,
Sara/0000-0003-4691-2630; Biddle, Andrea/0000-0003-0273-7439; Goold,
Susan Dorr/0000-0002-0258-9774
FU Intramural NIH HHS [ZIA CL010529-04]
NR 49
TC 6
Z9 6
U1 0
U2 7
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0894-587X
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD MAY
PY 2012
VL 39
IS 3
BP 158
EP 169
DI 10.1007/s10488-011-0341-4
PG 12
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 919KC
UT WOS:000302323200002
PM 21452017
ER
PT J
AU Wei, Z
Range, R
Angerer, R
Angerer, L
AF Wei, Zheng
Range, Ryan
Angerer, Robert
Angerer, Lynne
TI Axial patterning interactions in the sea urchin embryo: suppression of
nodal by Wnt1 signaling
SO DEVELOPMENT
LA English
DT Article
DE Strongylocentrotus purpuratus; Wnt1; Embryonic axes; Nodal; Sea urchin
ID GENE REGULATORY NETWORK; NUCLEAR BETA-CATENIN; ORAL-ABORAL AXIS;
STRONGYLOCENTROTUS-PURPURATUS; ANIMAL-VEGETAL; ENDODERM; SPECIFICATION;
GASTRULATION; EXPRESSION; ECTODERM
AB Wnt and Nodal signaling pathways are required for initial patterning of cell fates along anterior-posterior (AP) and dorsal-ventral (DV) axes, respectively, of sea urchin embryos during cleavage and early blastula stages. These mechanisms are connected because expression of nodal depends on early Wnt/beta-catenin signaling. Here, we show that an important subsequent function of Wnt signaling is to control the shape of the nodal expression domain and maintain correct specification of different cell types along the axes of the embryo. In the absence of Wnt1, the posterior-ventral region of the embryo is severely altered during early gastrulation. Strikingly, at this time, nodal and its downstream target genes gsc and bra are expressed ectopically, extending posteriorly to the blastopore. They override the initial specification of posterior-ventral ectoderm and endoderm fates, eliminating the ventral contribution to the gut and displacing the ciliary band dorsally towards, and occasionally beyond, the blastopore. Consequently, in Wnt1 morphants, the blastopore is located at the border of the re-specified posterior-ventral oral ectoderm and by larval stages it is in the same plane near the stomodeum on the ventral side. In normal embryos, a Nodal-dependent process downregulates wnt1 expression in dorsal posterior cells during early gastrulation, focusing Wnt1 signaling to the posterior-ventral region where it suppresses nodal expression. These subsequent interactions between Wnt and Nodal signaling are thus mutually antagonistic, each limiting the range of the other's activity, in order to maintain and stabilize the body plan initially established by those same signaling pathways in the early embryo.
C1 [Wei, Zheng; Range, Ryan; Angerer, Robert; Angerer, Lynne] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20891 USA.
RP Angerer, L (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20891 USA.
EM langerer@mail.nih.gov
FU Division of Intramural Research in the National Institute for Dental and
Craniofacial Research of the National Institutes of Health [ZO1
DE000712]
FX This work was supported by the Division of Intramural Research in the
National Institute for Dental and Craniofacial Research of the National
Institutes of Health [ZO1 DE000712]. Deposited in PMC for release after
12 months.
NR 51
TC 9
Z9 9
U1 0
U2 17
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAY 1
PY 2012
VL 139
IS 9
BP 1662
EP 1669
DI 10.1242/dev.075051
PG 8
WC Developmental Biology
SC Developmental Biology
GA 919XV
UT WOS:000302366400013
PM 22438568
ER
PT J
AU Linehan, WM
AF Linehan, W. Marston
TI The Genetic Basis of Kidney Cancer: Implications for Management and Use
of Targeted Therapeutic Approaches
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID DISEASE; IDENTIFICATION; CARCINOMA
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bldg 10,CRC Rm 1-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural NIH HHS [ZIA BC011043-05, ZIA BC011028-05, ZIA BC011038-05];
NCI NIH HHS [Z01 BC011089-01, Z01 BC011043-01, Z01 BC011028-01, Z01
BC011038-01]
NR 11
TC 4
Z9 4
U1 0
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 MAY
PY 2012
VL 61
IS 5
BP 896
EP 898
DI 10.1016/j.eururo.2012.02.022
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 918RJ
UT WOS:000302267900017
PM 22386837
ER
PT J
AU Ribeiro, JMC
Labruna, MB
Mans, BJ
Maruyama, SR
Francischetti, IMB
Barizon, GC
Santos, IKFD
AF Ribeiro, Jose Marcos C.
Labruna, Marcelo B.
Mans, Ben J.
Maruyama, Sandra Regina
Francischetti, Ivo M. B.
Barizon, Gustavo Canavaci
de Miranda Santos, Isabel K. F.
TI The sialotranscriptome of Antricola delacruzi female ticks is compatible
with non-hematophagous behavior and an alternative source of food
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Antricola delacruzi; Hematophagy; Scavenging; Transcriptome; Salivary
glands; Bat guano
ID SERUM-AMYLOID-A; BAT-GUANO; IXODES-SCAPULARIS; SALIVARY-GLAND; SOFT
TICK; BOOPHILUS-MICROPLUS; INSECTIVOROUS BATS; SEQUENCE ALIGNMENT;
ANOPHELES-GAMBIAE; FEEDING-BEHAVIOR
AB The hosts for Antricola delacruzi ticks are insectivorous, cave-dwelling bats on which only larvae are found. The mouthparts of nymphal and adult A. delacruzi are compatible with scavenging feeding because the hypostome is small and toothless. How a single blood meal of a larva provides energy for several molts as well as for oviposition by females is not known. Adults of A. delacruzi possibly feed upon an unknown food source in bat guano, a substrate on which nymphal and adult stages are always found. Guano produced by insectivorous bats contains twice the amount of protein and 60 times the amount of iron as beef. In addition, bacteria and chitin-rich fungi proliferate on guano. Comparative data on the transcriptome of the salivary glands of A. delacruzi is nonexistent and would help to understand the physiological adaptations of salivary glands that accompany different sources of food as well as the steps taken by the Acari toward haematophagy, believed to have evolved from scavenging dead animals. Annotation of the transcriptome of salivary glands from female instars of A. delacruzi collected on guano categorized 5.7% of the clusters of expressed genes as putative secreted proteins. They included abundantly expressed TIL-domain-containing proteins (possible anti-microbials), an abundantly expressed protein similar to a serum amyloid found in the sialotranscriptomes of Ornithodoros spp., a savignygrin, a family of mucin/peritrophin/cuticle-like proteins, anti-microbials and an HIV envelope-like glycoprotein also found in soft ticks. When comparing the transcriptome of A. delacruzi with those of blood-feeding female soft and hard ticks some notable differences were observed; they consisted of the following transcripts over- or under-represented or absent in the sialotranscriptome of A. delacruzi that may reflect its source of food: ferritin, mucins with chitin-binding domains and TIL-domain-containing proteins versus lipocalins, basic tail proteins, metalloproteases, glycine-rich proteins and Kunitz protease inhibitors, respectively. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [de Miranda Santos, Isabel K. F.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto, SP, Brazil.
[Ribeiro, Jose Marcos C.; Francischetti, Ivo M. B.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Labruna, Marcelo B.] Univ Sao Paulo, Sch Vet Med, Dept Prevent Vet Med & Anim Hlth, Sao Paulo, Brazil.
[Mans, Ben J.] Onderstepoort Vet Inst, Agr Res Council, Onderstepoort, South Africa.
[Mans, Ben J.] Univ Pretoria, Dept Vet Trop Dis, ZA-0002 Pretoria, South Africa.
RP Santos, IKFD (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto Sch Med, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil.
EM imsantos@fmrp.usp.br
RI Maruyama, Sandra/G-1171-2012; Labruna, Marcelo/B-6241-2013; de Miranda
Santos, Isabel/B-7597-2012; Ghartouchent, malek/B-9088-2012; Ribeiro,
Jose/J-7011-2015; de Miranda Santos, Isabel/D-5261-2016;
OI Labruna, Marcelo/0000-0002-9675-3132; de Miranda Santos,
Isabel/0000-0002-0438-4430; Mans, Ben/0000-0002-0177-0029; Maruyama,
Sandra/0000-0001-6807-1452; Ribeiro, Jose/0000-0002-9107-0818
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP
[2009/53645-3, 2007/59357-4]; Brazilian National Science Foundation-CNPq
[559603/2009-6, 302832/2007-6]; Division of Intramural Research;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Fundacao de Amparo a Pesquisa do Estado
de Sao Paulo-FAPESP through a grant. No 2009/53645-3 to IKFMS, and a
scholarship to SRM (No 2007/59357-4): by the Brazilian National Science
Foundation-CNPq through grants No 559603/2009-6 and No 47194612010-9 to
IKFMS, and No 302832/2007-6 to MBL, and the Intramural Research Program
of the Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health.
NR 83
TC 21
Z9 23
U1 2
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD MAY
PY 2012
VL 42
IS 5
BP 332
EP 342
DI 10.1016/j.ibmb.2012.01.003
PG 11
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 921ZE
UT WOS:000302515800003
PM 22306723
ER
PT J
AU Hwang, SK
Minai-Tehrani, A
Yu, KN
Chang, SH
Kim, JE
Lee, KH
Park, J
Beck, GR
Cho, MH
AF Hwang, Soon-Kyung
Minai-Tehrani, Arash
Yu, Kyeong-Nam
Chang, Seung-Hee
Kim, Ji-Eun
Lee, Kee-Ho
Park, Jongsun
Beck, George R., Jr.
Cho, Myung-Haing
TI Carboxyl-terminal modulator protein induces apoptosis by regulating
mitochondrial function in lung cancer cells
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE CTMP; apoptosis; mitochondria; lung cancer cells
ID CYTOCHROME-C; OPA1; DYNAMICS; AKT; PROLIFERATION; MORPHOLOGY; MEMBRANE;
PKB/AKT; RELEASE; PATHWAY
AB Serine/threonine protein kinase 13 (PKB/Akt) is involved in cell survival and growth. Carboxyl-terminal modulator protein (CTMP), a novel Akt binding partner, prevents Akt activation at the plasma membrane in response to various stimuli, and thus possesses a tumor suppressor-like function. In a previous study, we have demonstrated that CTMP inhibits tumor progression by facilitating apoptosis in a mouse lung cancer model. However, the precise mechanism of CTMP-induced apoptosis remains to be elucidated. The present study was performed to examine the role of CTMP in mitochondrial-mediated apoptosis and regulation of mitochondrial function in human lung carcinoma cells. Our results showed that CTMP altered mitochondrial morphology and caused the release of cytochrome c by inhibiting OPA1 expression. Additionally, CTMP facilitated mitochondrial-mediated apoptosis by inhibiting heat-shock protein 27 and preventing cytochrome c interaction with Apaf-1. Our data suggest that CTMP may therefore play a critical role in mitochondrial-mediated apoptosis in lung cancer cells.
C1 [Hwang, Soon-Kyung; Minai-Tehrani, Arash; Yu, Kyeong-Nam; Chang, Seung-Hee; Kim, Ji-Eun; Cho, Myung-Haing] Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea.
[Hwang, Soon-Kyung] NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Kim, Ji-Eun; Cho, Myung-Haing] Seoul Natl Univ, Dept Nano Fus Technol, Grad Sch Convergence Sci & Technol, Seoul 151742, South Korea.
[Cho, Myung-Haing] Seoul Natl Univ, Grad Grp Tumor Biol, Seoul 151742, South Korea.
[Lee, Kee-Ho] Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Mol Oncol Lab, Seoul 139240, South Korea.
[Park, Jongsun] Chungnam Natl Univ, Dept Pharmacol, Res Inst Med Sci, Coll Med,Canc Res Inst,Daejeon Reg Canc Ctr, Taejon 301131, South Korea.
[Beck, George R., Jr.] Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA.
RP Cho, MH (reprint author), Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea.
EM mchotox@snu.ac.kr
RI CHO, Myung-Haing/B-7362-2014; Park, Jongsun/E-7465-2010
OI Park, Jongsun/0000-0002-4690-1854
FU National Research Foundation of the Ministry of Education, Science and
Technology in South Korea [NRF-2010-0000784, 2011-0019175,
NRF-2011-0000380]; Research Institute for Veterinary Science of Seoul
National University
FX This work was supported partially by a research grant (NRF-2010-0000784,
2011-0019175 and NRF-2011-0000380) from the National Research Foundation
of the Ministry of Education, Science and Technology in South Korea.
This study was also partially supported by the Research Institute for
Veterinary Science of Seoul National University.
NR 27
TC 4
Z9 4
U1 0
U2 5
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAY
PY 2012
VL 40
IS 5
BP 1515
EP 1524
DI 10.3892/ijo.2011.1319
PG 10
WC Oncology
SC Oncology
GA 918TG
UT WOS:000302273400022
PM 22200884
ER
PT J
AU Newhauser, WD
Scheurer, ME
Faupel-Badger, JM
Clague, J
Weitzel, J
Woods, KV
AF Newhauser, Wayne D.
Scheurer, Michael E.
Faupel-Badger, Jessica M.
Clague, Jessica
Weitzel, Jeffrey
Woods, Kendra V.
TI The Future Workforce in Cancer Prevention: Advancing Discovery,
Research, and Technology
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Cancer prevention; Training; Workforce; Technology; Research
ID CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; PROTON-BEAMS; HEALTH-CARE; RISK;
PROGRAM; RADIOTHERAPY; IRRADIATION; STUDENTS; COST
AB As part of a 2-day conference on October 15 and 16, 2009, a nine-member task force composed of scientists, clinicians, educators, administrators, and students from across the USA was formed to discuss research, discovery, and technology obstacles to progress in cancer prevention and control, specifically those related to the cancer prevention workforce. This article summarizes the task force's findings on the current state of the cancer prevention workforce in this area and its needs for the future. The task force identified two types of barriers impeding the current cancer prevention workforce in research, discovery, and technology from reaching its fullest potential: (1) limited cross-disciplinary research opportunities with underutilization of some disciplines is hampering discovery and research in cancer prevention, and (2) new research avenues are not being investigated because technology development and implementation are lagging. Examples of impediments and desired outcomes are provided in each of these areas. Recommended solutions to these problems are based on the goals of enhancing the current cancer prevention workforce and accelerating the pace of discovery and clinical translation.
C1 [Newhauser, Wayne D.] Louisiana State Univ, Dept Phys & Astron, Med Phys Program, Baton Rouge, LA 70803 USA.
[Newhauser, Wayne D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Scheurer, Michael E.] Baylor Coll Med, Dept Pediat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA.
[Clague, Jessica; Weitzel, Jeffrey] City Hope Natl Med Ctr, Div Clin Canc Genet, Dept Populat Sci, Duarte, CA 91010 USA.
[Woods, Kendra V.] Univ Texas MD Anderson Canc Ctr, Off Acad Affairs, Houston, TX 77030 USA.
RP Newhauser, WD (reprint author), Louisiana State Univ, Dept Phys & Astron, Med Phys Program, 202 Nicholson Hall, Baton Rouge, LA 70803 USA.
EM newhauser@lsu.edu
OI Scheurer, Michael/0000-0002-8379-6088
FU National Cancer Institute [1 R01 CA131463-01A1, R25T CA57730, R25T
CA085771]; National Institute of Health [K07CA131505]
FX We thank Drs. E. Grubbs, M. Hildebrandt, S. Chang, and S. Tomasovic for
the helpful discussions and Ms. K. Carnes and Ms. S. Wilson for the
assistance in preparing this manuscript. This work was funded in part by
a grant from the National Cancer Institute (awards 1 R01 CA131463-01A1,
R25T CA57730 and R25T CA085771) and by the National Institute of Health
(award K07CA131505).
NR 49
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAY
PY 2012
VL 27
SU 2
BP 128
EP 135
DI 10.1007/s13187-012-0328-1
PG 8
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 919QZ
UT WOS:000302344800003
ER
PT J
AU Harrop, JP
Nelson, DE
Kuratani, DG
Mullen, PD
Paskett, ED
AF Harrop, J. Phil
Nelson, David E.
Kuratani, Darrah Goo
Mullen, Patricia Dolan
Paskett, Electra D.
TI Translating Cancer Prevention and Control Research into the Community
Setting: Workforce Implications
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Cancer prevention; Cancer control; Community-based participatory
research; Dissemination; Cancer workforce
ID HEALTH-PROMOTION RESEARCH; OF-THE-LITERATURE; PARTICIPATORY RESEARCH;
UNITED-STATES; IMPLEMENTATION RESEARCH; DISSEMINATION; RECOMMENDATIONS;
INTERVENTIONS; DISPARITIES; SHORTAGE
AB A gap exists between cancer prevention research and its translation into community practice. Two strategies to reduce this gap are community-based participatory research (CBPR) and dissemination research. CBPR offers an avenue to engage academic and community partners, thereby providing mechanisms for joint learning and application of knowledge. Dissemination research examines the movement of evidence-based public health and clinical innovations to practice settings. While applying these approaches may reduce the gap between research and practice, the cancer prevention workforce may be inadequate in size, insufficiently trained, lack resources and incentives, or face structural barriers to effectively participate in CBPR and disseminate evidence-based research findings into practice. Information on translating cancer prevention information to communities and workforce implications was obtained from a panel of experts and through a review of the literature on CBPR and dissemination research. The expert panel and literature review identified major barriers to successfully conducting CBPR and dissemination research in community settings. Barriers included inadequate policies; insufficient networking and communication infrastructures; unsupportive research cultures, climates, and mindsets; inadequate researcher and practitioner education; and limited CBPR and dissemination research with adequate study designs. No specific estimates of the cancer prevention workforce were found; however, indirect evidence for a shortfall were identified. We recommend expanding CBPR training for academic and community partners; increasing funding for dissemination research and practice; supporting proven partnerships; and providing strategic coordination for government agencies, research institutions, nongovernmental organizations, and the private sector to foster better dissemination of information and integration of community-based cancer prevention and control programs and practices. Specific challenges and needs that must be addressed to improve the translation of cancer prevention research into community settings were identified.
C1 [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Coll Publ Hlth, Coll Med, Columbus, OH 43201 USA.
[Harrop, J. Phil] Ohio State Univ, Ctr Comprehens Canc, Div Hlth Serv Management & Policy, Coll Publ Hlth, Columbus, OH 43201 USA.
[Nelson, David E.] NCI, Rockville, MD 20852 USA.
[Kuratani, Darrah Goo] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Mullen, Patricia Dolan] Univ Texas Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA.
RP Paskett, ED (reprint author), Ohio State Univ, Ctr Comprehens Canc, Coll Publ Hlth, Coll Med, 1590 N High St,Suite 525, Columbus, OH 43201 USA.
EM Electra.Paskett@osumc.edu
NR 42
TC 3
Z9 3
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAY
PY 2012
VL 27
SU 2
BP 157
EP 164
DI 10.1007/s13187-012-0329-0
PG 8
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 919QZ
UT WOS:000302344800007
ER
PT J
AU Leckman, JF
Pine, DS
AF Leckman, James F.
Pine, Daniel S.
TI Editorial Commentary: Challenges and potential of DSM-5 and ICD-11
revisions
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Editorial Material
ID DISORDERS; CHILDREN; PSYCHOPATHOLOGY; ADOLESCENTS; PREVALENCE
C1 [Leckman, James F.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Leckman, James F.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Leckman, James F.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Leckman, James F.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
RP Leckman, JF (reprint author), Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
NR 27
TC 3
Z9 4
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD MAY
PY 2012
VL 53
IS 5
BP 449
EP 453
DI 10.1111/j.1469-7610.2012.02548.x
PG 5
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 921FF
UT WOS:000302462800001
PM 22486485
ER
PT J
AU Addington, AM
Rapoport, JL
AF Addington, Anjene M.
Rapoport, Judith L.
TI Annual Research Review: Impact of advances in genetics in understanding
developmental psychopathology
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Review
DE Developmental psychopathology; genetics; copy number variants; pre-natal
diagnosis; nosology; prevention
ID AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION;
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CHILDHOOD-ONSET SCHIZOPHRENIA;
SCAFFOLDING PROTEIN SHANK3; FRAGILE-X-SYNDROME; PSYCHIATRIC-DISORDERS;
MENTAL-RETARDATION; COMMON VARIANTS; MUTATIONS
AB It was hoped that diagnostic guidelines for, and treatment of, child psychiatric disorders in DSM-5 would be informed by the wealth of clinical genetic research related to neurodevelopmental disorders. In spite of remarkable advances in genetic technology, this has not been the case. Candidate gene, genome-wide association, and rare copy number variant (CNV) studies have been carried out for attention-deficit/hyperactivity disorder (ADHD), Autism, Tourettes Syndrome, and schizophrenia, with intriguing results, but environmental factors, incomplete penetrance, pleiotropy, and genetic heterogeneity, underlying any given phenotype have limited clinical translation. One promising approach may be the use of developmental brain imaging measures as more relevant phenotypes. This is particularly important, as subtle abnormalities in timing and expression of gene pathways underlying brain development may well link these disorders and be the ultimate target of treatments.
C1 [Addington, Anjene M.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Rapoport, JL (reprint author), 10 Ctr Dr,Room 3N202, Bethesda, MD 20892 USA.
EM rapoporj@mail.nih.gov
FU NIH
FX This manuscript is based on material funded by the NIH.
NR 96
TC 19
Z9 19
U1 2
U2 26
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD MAY
PY 2012
VL 53
IS 5
BP 510
EP 518
DI 10.1111/j.1469-7610.2011.02478.x
PG 9
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 921FF
UT WOS:000302462800005
PM 22067053
ER
PT J
AU Ferrari, PF
Vanderwert, RE
Paukner, A
Bower, S
Suomi, SJ
Fox, NA
AF Ferrari, Pier Francesco
Vanderwert, Ross E.
Paukner, Annika
Bower, Seth
Suomi, Stephen J.
Fox, Nathan A.
TI Distinct EEG Amplitude Suppression to Facial Gestures as Evidence for a
Mirror Mechanism in Newborn Monkeys
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID INFERIOR PARIETAL; PREMOTOR CORTEX; MOTOR CORTEX; MU-RHYTHMS; IMITATION;
EXECUTION; NEURONS; SYSTEM; OSCILLATIONS; PERCEPTION
AB At birth, human infants and newborns of other primate species demonstrate the capacity to attend and to respond to facial stimuli provided by a caregiver. Newborn infants are also capable of exhibiting a range of facial expressions. Identification of the neural underpinnings of these capacities represents a formidable challenge in understanding social development. One possible neuronal substrate is the mirror-neuron system assumed to activate shared motor cortical representations for both observation and production of actions. We tested this hypothesis by recording scalp EEG from 1- to 7-day-old newborn rhesus macaques who were observing and producing facial gestures. We found that 5-6 Hz EEG activity was suppressed both when the infants produced facial gestures and while they were observing facial gestures of a human experimenter, but not when they were observing nonbiological stimuli. These findings demonstrate the presence of neural reactivity for biological, communicatively relevant stimuli, which may be a likely signature of neuronal mirroring. The basic elements of the mirror-neuron system appear to operate from the very first days of life and contribute to the encoding of socially relevant stimuli.
C1 [Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Vanderwert, Ross E.; Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
[Paukner, Annika; Bower, Seth; Suomi, Stephen J.] NIH, Poolesville, MD USA.
RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Neurosci, Via Volturno 39, I-43100 Parma, Italy.
EM pierfrancesco.ferrari@unipr.it
OI Vanderwert, Ross/0000-0002-2280-8401
FU NIH [P01HD064653-01]; Division of Intramural Research, NICHD
FX We thank Giacomo Rizzolatti, Leonardo Fogassi, and Riitta Hari for
useful comments on an earlier version of the manuscript. This research
was supported by P01HD064653-01 NIH grant to F. P. F. and N. A. F. and
the Division of Intramural Research, NICHD.
NR 37
TC 34
Z9 36
U1 1
U2 15
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD MAY
PY 2012
VL 24
IS 5
BP 1165
EP 1172
PG 8
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 918NI
UT WOS:000302256300011
PM 22288390
ER
PT J
AU Baird, K
Booher, S
Comis, L
Joe, G
Steinberg, SM
Figg, WD
Spencer, SD
Takebe, N
Pavletic, S
Cowen, EW
AF Baird, K.
Booher, S.
Comis, L.
Joe, G.
Steinberg, S. M.
Figg, W. D.
Spencer, S. D.
Takebe, N.
Pavletic, S.
Cowen, E. W.
TI Imatinib mesylate for the treatment of sclerotic skin chronic
graft-versus-host disease
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Baird, K.; Booher, S.; Comis, L.; Joe, G.; Steinberg, S. M.; Figg, W. D.; Spencer, S. D.; Takebe, N.; Pavletic, S.; Cowen, E. W.] NIH, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 518
BP S88
EP S88
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900520
ER
PT J
AU Colmont, CS
Ben Ketah, A
Errington, R
Yee, CL
Udey, M
Vogel, JC
Patel, GK
AF Colmont, C. S.
Ben Ketah, A.
Errington, R.
Yee, C. L.
Udey, M.
Vogel, J. C.
Patel, G. K.
TI Human basal cell carcinoma tumor initiating cells express MDR1 and are
resistant to etoposide killing
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Errington, R.] Cardiff Univ, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
[Yee, C. L.; Udey, M.; Vogel, J. C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 124
BP S21
EP S21
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900123
ER
PT J
AU Cui, C
Childress, V
Piao, Y
Michel, M
Johnson, AA
Kunisada, M
Ko, MS
Kaestner, KH
Marmorstein, AD
Schlessinger, D
AF Cui, C.
Childress, V.
Piao, Y.
Michel, M.
Johnson, A. A.
Kunisada, M.
Ko, M. S.
Kaestner, K. H.
Marmorstein, A. D.
Schlessinger, D.
TI Forkhead transcription factor FoxA1 regulates sweat secretion through
Best2 and Nkcc1 ion transporters
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Cui, C.; Childress, V.; Piao, Y.; Michel, M.; Ko, M. S.; Schlessinger, D.] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Johnson, A. A.; Marmorstein, A. D.] Univ Arizona, Dept Ophthalmol & Vis Sci, Tucson, AZ USA.
[Kunisada, M.] Kobe Univ, Div Dermatol, Kobe, Hyogo 657, Japan.
[Kaestner, K. H.] Univ Penn, Dept Genet, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
RI Ko, Minoru/B-7969-2009
OI Ko, Minoru/0000-0002-3530-3015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 472
BP S80
EP S80
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900474
ER
PT J
AU Daily, K
Patel, VR
Rigor, P
Xie, X
Baldi, P
AF Daily, K.
Patel, V. R.
Rigor, P.
Xie, X.
Baldi, P.
TI MotifMap: Integrative genome-wide maps of regulatory motif sites for
model species
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Daily, K.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Daily, K.; Patel, V. R.; Rigor, P.; Xie, X.; Baldi, P.] UC Irvine, Dept Comp Sci, Irvine, CA USA.
[Daily, K.; Patel, V. R.; Rigor, P.; Xie, X.; Baldi, P.] UC Irvine, Inst Genom & Bioinformat, Irvine, CA USA.
[Baldi, P.] UC Irvine, Dept Dev & Cell Biol, Irvine, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 417
BP S71
EP S71
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900420
ER
PT J
AU Duverger, O
Zah, A
Isaac, J
Sun, H
Lian, JB
Berdal, A
Hwang, J
Morasso, MI
AF Duverger, O.
Zah, A.
Isaac, J.
Sun, H.
Lian, J. B.
Berdal, A.
Hwang, J.
Morasso, M. I.
TI Dissection of Dlx3 function in ectodermal appendage development: Impacts
of mesenchymal and epithelial-specific deletions on tooth development
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Duverger, O.; Zah, A.; Isaac, J.; Hwang, J.; Morasso, M. I.] NIAMS, NIH, Dev Skin Biol Sect, Bethesda, MD USA.
[Sun, H.] NIAMS, NIH, Biodata Min & Discovery Sect, Bethesda, MD USA.
[Lian, J. B.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA.
[Lian, J. B.] Univ Massachusetts, Sch Med, Dept Orthoped Surg, Worcester, MA 01655 USA.
[Berdal, A.] INSERM, Lab Mol Oral Physiopathol, UMRS 872, Paris, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 398
BP S68
EP S68
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900399
ER
PT J
AU Gaiser, MR
Lammermann, T
Feng, X
Igyarto, BZ
Kaplan, DH
Tessarollo, L
Germain, RN
Udey, MC
AF Gaiser, M. R.
Laemmermann, T.
Feng, X.
Igyarto, B. Z.
Kaplan, D. H.
Tessarollo, L.
Germain, R. N.
Udey, M. C.
TI EpCAM (CD326) enables epidermal Langerhans cell motility and migration
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Gaiser, M. R.; Feng, X.; Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gaiser, M. R.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany.
[Laemmermann, T.; Germain, R. N.] NIAID, Lab Syst Biol, Bethesda, MD 20892 USA.
[Igyarto, B. Z.; Kaplan, D. H.] Univ Minnesota, Dept Dermatol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Tessarollo, L.] NCI, Mouse Canc Genet Programm, Ctr Canc Res, Frederick, MD 21701 USA.
RI Kaplan, Daniel/N-2779-2013
OI Kaplan, Daniel/0000-0002-7851-7320
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 578
BP S98
EP S98
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900577
ER
PT J
AU Inozume, T
Furuta, J
Hanada, K
Shimada, S
AF Inozume, T.
Furuta, J.
Hanada, K.
Shimada, S.
TI Enhanced NGFR signal in melanoma cells suppresses the tumor recognition
by melanoma specific T cells
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Inozume, T.; Furuta, J.; Shimada, S.] Univ Yamanashi, Tamaho, Yamanashi, Japan.
[Hanada, K.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 571
BP S97
EP S97
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900573
ER
PT J
AU Khan, SG
Tamura, D
Rao, T
Zein, WM
Brooks, BP
Boyle, J
Ueda, T
DiGiovanna, JJ
Kraemer, KH
AF Khan, S. G.
Tamura, D.
Rao, T.
Zein, W. M.
Brooks, B. P.
Boyle, J.
Ueda, T.
DiGiovanna, J. J.
Kraemer, K. H.
TI Patients with the rare DNA repair disease overlap syndrome xeroderma
pigmentosum and trichothiodystrophy (XP/TTD) are at high risk for skin
and internal cancers
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Khan, S. G.; Tamura, D.; Rao, T.; Boyle, J.; Ueda, T.; DiGiovanna, J. J.; Kraemer, K. H.] NCI, Derm Branch, Bethesda, MD 20892 USA.
[Zein, W. M.; Brooks, B. P.] NEI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 412
BP S70
EP S70
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900412
ER
PT J
AU Kim, J
Hwang, J
Morasso, MI
AF Kim, J.
Hwang, J.
Morasso, M. I.
TI Dlx3 is a critical regulator on hair follicle differentiation and
development
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Kim, J.; Morasso, M. I.] NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 449
BP S76
EP S76
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900448
ER
PT J
AU Kiss, A
Koppel, AC
Anders, J
Cataisson, C
Yuspa, SH
Efimova, T
AF Kiss, A.
Koppel, A. C.
Anders, J.
Cataisson, C.
Yuspa, S. H.
Efimova, T.
TI Keratinocyte-specific p38 delta mitogen-activated protein kinase (MAPK)
deletion reveals a context and gender dependent regulation of skin
carcinogenesis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Kiss, A.; Koppel, A. C.; Efimova, T.] Washington Univ, Sch Med, St Louis, MO USA.
[Anders, J.; Cataisson, C.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 130
BP S22
EP S22
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900129
ER
PT J
AU Kong, HH
Oh, J
Conlan, S
Deming, C
Grice, EA
Turner, ML
Segre, JA
AF Kong, H. H.
Oh, J.
Conlan, S.
Deming, C.
Grice, E. A.
Turner, M. L.
Segre, J. A.
TI Temporal shifts in the skin microbiome associated with atopic dermatitis
disease flares and treatment
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Kong, H. H.; Turner, M. L.] NIH, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Oh, J.; Conlan, S.; Deming, C.; Grice, E. A.; Segre, J. A.] NHGRI, GMBB, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 665
BP S113
EP S113
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900668
ER
PT J
AU Kuschal, C
DiGiovanna, JJ
Khan, SG
Kraemer, KH
AF Kuschal, C.
DiGiovanna, J. J.
Khan, S. G.
Kraemer, K. H.
TI Restoration of XPC protein and induction of DNA repair in homozygous and
heterozygous xeroderma pigmentosum group C cells by readthrough of stop
codons using aminoglycoside compounds
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Kuschal, C.; DiGiovanna, J. J.; Khan, S. G.; Kraemer, K. H.] NCI, Derm Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 411
BP S70
EP S70
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900414
ER
PT J
AU Li, L
Ansbro, M
Shukla, S
Ambudkar, S
Blumberg, P
Yuspa, SH
AF Li, L.
Ansbro, M.
Shukla, S.
Ambudkar, S.
Blumberg, P.
Yuspa, S. H.
TI Identification of protein kinase C activating phorbol ester and ingenol
derivatives as candidates for cutaneous P-glycoprotein absorptive
transport across the epidermis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Li, L.; Ansbro, M.; Shukla, S.; Ambudkar, S.; Blumberg, P.; Yuspa, S. H.] NCI, LCBG, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 139
BP S24
EP S24
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900142
ER
PT J
AU Li, S
Liu, Y
Wang, J
Moss, J
Darling, TN
AF Li, S.
Liu, Y.
Wang, J.
Moss, J.
Darling, T. N.
TI Tuberous sclerosis skin tumor cells express high levels of cathepsins B,
K, and L
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Li, S.; Liu, Y.; Wang, J.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Moss, J.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 196
BP S33
EP S33
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900195
ER
PT J
AU Mabuchi, T
Singh, T
Takekoshi, T
Farber, J
Hwang, S
AF Mabuchi, T.
Singh, T.
Takekoshi, T.
Farber, J.
Hwang, S.
TI CCR6 is required for epidermal trafficking of (and IL22 production by)
gamma delta-low T cells in an IL23-induced model of psoriasiform
dermatitis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Mabuchi, T.; Takekoshi, T.; Hwang, S.] Med Coll WI, Milwaukee, WI USA.
[Singh, T.; Farber, J.] NIAID, Inflammat Biol Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 583
BP S99
EP S99
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900585
ER
PT J
AU Masaki, T
DiGiovanna, JJ
Wang, Y
Khan, SG
Hornyak, T
Lee, C
Kraemer, KH
AF Masaki, T.
DiGiovanna, J. J.
Wang, Y.
Khan, S. G.
Hornyak, T.
Lee, C.
Kraemer, K. H.
TI Mutation analysis of pre-malignant and malignant pigmented lesions in
xeroderma pigmentosum: The role of UV damage in melanoma induction
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Masaki, T.; DiGiovanna, J. J.; Wang, Y.; Khan, S. G.; Hornyak, T.; Kraemer, K. H.] NCI, Derm Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 732
BP S125
EP S125
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900731
ER
PT J
AU Miyagawa, F
Tagaya, Y
Ozato, K
Katz, SI
AF Miyagawa, F.
Tagaya, Y.
Ozato, K.
Katz, S. I.
TI IRF8 controls activation-induced cell death on CD8 T cells by regulating
Bcl2
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Miyagawa, F.; Tagaya, Y.; Ozato, K.; Katz, S. I.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 572
BP S97
EP S97
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900571
ER
PT J
AU Mohammed, J
Gunderson, A
Khong, L
Koubek, R
Udey, M
Glick, A
AF Mohammed, J.
Gunderson, A.
Khong, L.
Koubek, R.
Udey, M.
Glick, A.
TI Overexpression of TGF beta 1 in murine epidermis alters skin dendritic
cell homeostasis and enhances adaptive immunity
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Mohammed, J.; Gunderson, A.; Khong, L.; Koubek, R.; Glick, A.] Penn State Univ, University Pk, PA 16802 USA.
[Udey, M.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 609
BP S103
EP S103
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900610
ER
PT J
AU Motegi, S
Ishikawa, O
Udey, MC
AF Motegi, S.
Ishikawa, O.
Udey, M. C.
TI Expression of MFG-E8 in murine and human skin
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Motegi, S.; Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Motegi, S.; Ishikawa, O.] Gunma Univ, Grad Sch Med, Dept Dermatol, Maebashi, Gumma 371, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 184
BP S31
EP S31
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900183
ER
PT J
AU Nagao, K
Kobayashi, T
Moro, K
Kabashima, K
Ohyama, M
Cho, Y
Clausen, BE
Udey, MC
Amagai, M
AF Nagao, K.
Kobayashi, T.
Moro, K.
Kabashima, K.
Ohyama, M.
Cho, Y.
Clausen, B. E.
Udey, M. C.
Amagai, M.
TI Dendritic cell trafficking in skin is regulated by hair follicles via
chemokine production
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Nagao, K.; Kobayashi, T.; Moro, K.; Ohyama, M.; Amagai, M.] Keio Univ, Sch Med, Tokyo, Japan.
[Kabashima, K.] Kyoto Univ, Kyoto, Japan.
[Clausen, B. E.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Cho, Y.; Udey, M. C.] NCI, CCR, NIH, Bethesda, MD 20892 USA.
RI Kabashima, Kenji/G-2521-2014; Moro, Kazuyo/A-5987-2016
OI Kabashima, Kenji/0000-0002-0773-0554;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 585
BP S99
EP S99
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900586
ER
PT J
AU Okano, J
Lichti, U
Mamiya, S
Aronova, M
Zhang, G
Yuspa, SH
Hamada, H
Sakai, Y
Morasso, MI
AF Okano, J.
Lichti, U.
Mamiya, S.
Aronova, M.
Zhang, G.
Yuspa, S. H.
Hamada, H.
Sakai, Y.
Morasso, M. I.
TI Increased retinoic acid levels through ablation of Cyp26b1 determine the
processes of embryonic skin barrier formation and peridermal development
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Okano, J.; Morasso, M. I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA.
[Lichti, U.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Mamiya, S.; Hamada, H.] Osaka Univ, Dev Genet Grp, Grad Sch Frontier Biosci, Osaka, Japan.
[Aronova, M.; Zhang, G.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
[Sakai, Y.] Osaka Univ, Sch Med, Dept Plast Surg, Osaka, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 313
BP S53
EP S53
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900312
ER
PT J
AU Okiyama, N
Furumoto, Y
Villarroel, V
Gutermuth, J
Ghoreschi, K
Gadina, M
Katz, SI
AF Okiyama, N.
Furumoto, Y.
Villarroel, V.
Gutermuth, J.
Ghoreschi, K.
Gadina, M.
Katz, S. I.
TI Effective prevention and treatment of CD8 T cell-mediated
Graft-versus-host-like disease (GvHD) using a JAK inhibitor
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Okiyama, N.; Villarroel, V.; Gutermuth, J.; Katz, S. I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Furumoto, Y.; Gutermuth, J.; Ghoreschi, K.] NIAMS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 040
BP S7
EP S7
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900042
ER
PT J
AU Qian, Y
Jeong, JS
Maldonado, M
Evangelista, F
Qaqish, BF
Aoki, V
Hans, G
Rivitti, EA
Valenzuela, JG
Diaz, LA
AF Qian, Y.
Jeong, J. S.
Maldonado, M.
Evangelista, F.
Qaqish, B. F.
Aoki, V.
Hans-Filhio, G.
Rivitti, E. A.
Valenzuela, J. G.
Diaz, L. A.
TI Anti-Desmoglein 1 autoantibodies from Fogo Selvagem recognize LJM11, a
member of the "yellow" family of salivary proteins from Lutzomyia
longipalpis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Qian, Y.; Jeong, J. S.; Maldonado, M.; Evangelista, F.; Qaqish, B. F.; Diaz, L. A.] Univ N Carolina, Chapel Hill, NC USA.
[Aoki, V.; Rivitti, E. A.] Univ Sao Paulo, Sao Paulo, Brazil.
[Hans-Filhio, G.] Univ Mato Grosso do Sul, Mato Grosso, Brazil.
[Valenzuela, J. G.] NIAID, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 054
BP S9
EP S9
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900055
ER
PT J
AU Richardson, BS
Anderson, WF
Barnholtz-Sloan, JS
Tucker, MA
Gerstenblith, MR
AF Richardson, B. S.
Anderson, W. F.
Barnholtz-Sloan, J. S.
Tucker, M. A.
Gerstenblith, M. R.
TI Gender is an age-specific effect modifier for ulcerated malignant
melanomas
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Barnholtz-Sloan, J. S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA.
[Anderson, W. F.] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA.
[Tucker, M. A.] NCI, Human Genet Program, NIH, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 282
BP S48
EP S48
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900285
ER
PT J
AU Sekulic, A
Zismann, V
Froman, R
Allen, A
Huentleman, M
Paoloni, M
Neff, M
Davis, B
Cox, A
Duesbery, N
Xu, J
Bittner, M
Webb, C
Brown, K
LoRusso, P
Trent, J
AF Sekulic, A.
Zismann, V.
Froman, R.
Allen, A.
Huentleman, M.
Paoloni, M.
Neff, M.
Davis, B.
Cox, A.
Duesbery, N.
Xu, J.
Bittner, M.
Webb, C.
Brown, K.
LoRusso, P.
Trent, J.
TI Efforts to provide a comprehensive overview of genetic changes in canine
melanoma as a means to identify genetic correlates for drug response
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Sekulic, A.; Zismann, V.; Allen, A.; Huentleman, M.; Bittner, M.; Trent, J.] Tgen, Phoenix, AZ USA.
[Sekulic, A.] Mayo Clin, Scottsdale, AZ USA.
[Froman, R.; Neff, M.; Cox, A.; Duesbery, N.; Webb, C.] Van Andel Res Inst, Grand Rapids, MI USA.
[Paoloni, M.; Brown, K.] NCI, Bethesda, MD 20892 USA.
[Davis, B.] Tufts Univ, Medford, MA 02155 USA.
[Xu, J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA.
RI Webb, Craig/I-8123-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 781
BP S133
EP S133
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900782
ER
PT J
AU Singh, A
Trempus, CS
Morris, RJ
AF Singh, A.
Trempus, C. S.
Morris, R. J.
TI Identification of novel mutations in the candidate keratinocyte stem
cell regulatory gene, Bone Morphogenetic Protein 5
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Singh, A.; Morris, R. J.] Univ Minnesota, Hormel Inst, Lab Stem Cells & Canc, Austin, MN 55912 USA.
[Trempus, C. S.] NIEHS, Matrix Biol Grp, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 830
BP S142
EP S142
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900830
ER
PT J
AU Tan, X
Anzick, S
Khan, SG
Ueda, T
Stone, G
DiGiovanna, JJ
Tamura, D
Wattendorf, D
Walker, R
Meltzer, P
Kraemer, KH
AF Tan, X.
Anzick, S.
Khan, S. G.
Ueda, T.
Stone, G.
DiGiovanna, J. J.
Tamura, D.
Wattendorf, D.
Walker, R.
Meltzer, P.
Kraemer, K. H.
TI Chimeric 9p-22q transcript in a patient with melanoma and DNA repair
deficiency acts as a negative regulator of p14ARF
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Tan, X.; Khan, S. G.; Ueda, T.; DiGiovanna, J. J.; Tamura, D.; Kraemer, K. H.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
[Anzick, S.; Stone, G.; Walker, R.; Meltzer, P.] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Wattendorf, D.] USAF, Off Surgeon Gen, Washington, DC 20330 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 741
BP S127
EP S127
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900744
ER
PT J
AU Tomita, T
Putney, JW
AF Tomita, T.
Putney, J. W.
TI STIM1 and Orai1-mediated store-operated Ca2+ entry is critical for
Ca2+-switch-induced keratinocyte differentiation
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Tomita, T.; Putney, J. W.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 370
BP S63
EP S63
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900373
ER
PT J
AU Totonchy, MB
Tamura, D
Zalewski, C
Bradford, PT
DiGiovanna, JJ
Kraemer, KH
Brewer, CC
AF Totonchy, M. B.
Tamura, D.
Zalewski, C.
Bradford, P. T.
DiGiovanna, J. J.
Kraemer, K. H.
Brewer, C. C.
TI DNA repair is critical in maintaining neurologic integrity and hearing
function: A 40 yr longitudinal auditory analysis of patients with
xeroderma pigmentosum and trichothiodystrophy
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Totonchy, M. B.; Tamura, D.; DiGiovanna, J. J.; Kraemer, K. H.] NCI, Derm Branch, Bethesda, MD 20892 USA.
[Totonchy, M. B.] NIH, Bethesda, MD 20892 USA.
[Zalewski, C.; Brewer, C. C.] NIDCD, Otolaryngol Br, Bethesda, MD USA.
[Bradford, P. T.] NCI, Genet Epi Br, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 251
BP S43
EP S43
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900252
ER
PT J
AU Trempus, CS
Flake, GP
Kissling, GE
Stober, V
Zhuo, L
Kimata, K
Garantziotis, S
AF Trempus, C. S.
Flake, G. P.
Kissling, G. E.
Stober, V.
Zhuo, L.
Kimata, K.
Garantziotis, S.
TI Dysregulated wound healing in inter-alpha-trypsin inhibitor deficient
mice
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Trempus, C. S.; Stober, V.; Garantziotis, S.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Flake, G. P.] NIEHS, Comparat & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Kissling, G. E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Zhuo, L.; Kimata, K.] Aichi Med Univ, Nagakute, Aichi, Japan.
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 800
BP S137
EP S137
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900801
ER
PT J
AU Wheless, L
Kistner-Griffin, E
Jorgensen, TJ
Berthier-Schaad, Y
Kessing, B
Hoffman-Bolton, J
Shugart, YY
Kao, W
Strickland, PT
Francis, L
Alani, RM
Smith, MW
Alberg, AJ
AF Wheless, L.
Kistner-Griffin, E.
Jorgensen, T. J.
Berthier-Schaad, Y.
Kessing, B.
Hoffman-Bolton, J.
Shugart, Y. Y.
Kao, W.
Strickland, P. T.
Francis, L.
Alani, R. M.
Smith, M. W.
Alberg, A. J.
TI Gene-gene interactions between nucleotide excision repair RPA3 with XPC
and ERCC1 are associated with risk of nonmelanoma skin cancer
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Wheless, L.; Kistner-Griffin, E.; Francis, L.; Alberg, A. J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Berthier-Schaad, Y.] NCI, Frederick, MD 21701 USA.
[Shugart, Y. Y.] NIMH, Bethesda, MD 20892 USA.
[Alani, R. M.] Boston Univ, Boston, MA 02215 USA.
[Kessing, B.; Smith, M. W.] SAIC Frederick Inc, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 155
BP S26
EP S26
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900156
ER
PT J
AU Xiao, Y
Woo, W
Terunuma, A
Oro, AE
Vogel, JC
Brownell, I
AF Xiao, Y.
Woo, W.
Terunuma, A.
Oro, A. E.
Vogel, J. C.
Brownell, I.
TI A perivascular stem cell niche in the hair follicle
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 75th Annual Meeting of the Society-for-Investigative-Dermatology
CY MAY 09-12, 2012
CL Raleigh, NC
SP Soc Investigat Dermatol
C1 [Xiao, Y.; Terunuma, A.; Vogel, J. C.; Brownell, I.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Woo, W.; Oro, A. E.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2012
VL 132
SU 1
MA 467
BP S79
EP S79
PG 1
WC Dermatology
SC Dermatology
GA 926XV
UT WOS:000302866900466
ER
PT J
AU Rao, JS
Kellom, M
Kim, HW
Rapoport, SI
Reese, EA
AF Rao, Jagadeesh S.
Kellom, Matthew
Kim, Hyung-Wook
Rapoport, Stanley I.
Reese, Edmund A.
TI Neuroinflammation and Synaptic Loss
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Arachidonic acid; Cytokines; Drebrin; Synaptophysin; Excitotoxicity
ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; CYTOSOLIC PHOSPHOLIPASE
A(2); MILD COGNITIVE IMPAIRMENT; NF-KAPPA-B; ARACHIDONIC-ACID
METABOLISM; DENDRITIC SPINE PATHOLOGY; MESSENGER-RNA EXPRESSION;
CENTRAL-NERVOUS-SYSTEM; HIV-1 TRANSGENIC RATS
AB Neuroinflammation plays a critical role in the progression of many neurodegenerative, neuropsychiatric and viral diseases. In neuroinflammation, activated microglia and astrocytes release cytokines and chemokines as well as nitric oxide, which in turn activate many signal transduction pathways. The cytokines, interleukin-1 beta and tumor necrosis factor alpha, regulate transcription of a number of genes within the brain, which can lead to the formation of pro-inflammatory products of the arachidonic acid cascade. Formation of pro-inflammatory agents and associated cytotoxic products during neuroinflammation can be detrimental to neurons by altering synaptic proteins. Neuroinflammation as well as excitotoxic insults reduce synaptic markers such as synaptophysin and drebrin. Neurodegenerative, neuropsychiatric illnesses and viral infections are accompanied by loss of both pre- and post-synaptic proteins. These synaptic changes may contribute to the progressive cognitive decline and behavioral changes associated with these illnesses.
C1 [Rao, Jagadeesh S.; Kellom, Matthew; Kim, Hyung-Wook; Rapoport, Stanley I.; Reese, Edmund A.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Rm 1S126 MSC 0947, Bethesda, MD 20892 USA.
EM jrao@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health, Bethesda, MD
FX This research was entirely supported by the Intramural Research Programs
of the National Institute on Aging, National Institutes of Health,
Bethesda, MD 20892. We thank the National Cancer Institute (NCI), Center
for Cancer Research (CCR) Fellows Editorial Board for proofreading the
manuscript.
NR 98
TC 62
Z9 64
U1 0
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD MAY
PY 2012
VL 37
IS 5
BP 903
EP 910
DI 10.1007/s11064-012-0708-2
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 920LC
UT WOS:000302404900001
PM 22311128
ER
PT J
AU Lubet, RA
Clapper, ML
McCormick, DL
Pereira, MA
Chang, WCL
Steele, VE
Fischer, SM
Juliana, MM
Grubbs, CJ
AF Lubet, Ronald A.
Clapper, Margie L.
McCormick, David L.
Pereira, Michael A.
Chang, W-C L.
Steele, Vernon E.
Fischer, Susan M.
Juliana, M. Margaret
Grubbs, Clinton J.
TI Chemopreventive efficacy of Targretin in rodent models of urinary
bladder, colon/intestine, head and neck and mammary cancers
SO ONCOLOGY REPORTS
LA English
DT Article
DE cancer; Targretin; animal models; chemoprevention
ID LUNG CARCINOGENESIS; CELL-PROLIFERATION; PREVENTION; EXPRESSION;
LGD1069; CYCLOOXYGENASE-2; TRANSCRIPTION; BEXAROTENE; INHIBITORS;
APOPTOSIS
AB The chemopreventive efficacy of Targretin was evaluated in various rodent cancer models. In the rat model of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced urinary bladder cancer, it was found that Targretin administered in the diet (beginning one week after the last OH-BBN treatment) for 5.5 months increased the number and size of urinary bladder cancers. In the azoxymethane (AOM)-induced model of colon carcinogenesis (in which rats develop minimally invasive colonic cancers), Targretin was ineffective as a chemopreventive agent, decreasing neither tumor incidence nor multiplicity. Treatment of Min mice with Targretin for 45 days similarly failed to decrease the multiplicity of small intestinal tumors. Similarly, no preventive efficacy was noted for Targretin when the incidence of tumors in the head and neck model (squamous cell tongue tumors) induced by 4-nitroquinoline 1-oxide (4-NQO) were examined. In contrast, use of even a suboptimal dose of Targretin (40 ppm) in a sensitive breast cancer model [methylnitrosourea (MNU)-induced ER+ mammary cancers] reduced cancer multiplicity by 60%. Finally, based on the hypothesis that Targretin may decrease the expression of COX-2, the effects of Targretin and COX inhibitors were compared in these models. There was minimal overlap of efficacy. That is, models which were relatively susceptible to NSAIDs or COX-2 inhibitors tended not to be sensitive to Targretin and vice versa.
C1 [Lubet, Ronald A.; Steele, Vernon E.] NCI, Canc Prevent Div, Bethesda, MD 20852 USA.
[Clapper, Margie L.; Chang, W-C L.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA.
[Pereira, Michael A.] Ohio State Univ, Columbus, OH 43210 USA.
[McCormick, David L.] IIT Inst, Chicago, IL USA.
[Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Juliana, M. Margaret; Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL USA.
[Juliana, M. Margaret; Grubbs, Clinton J.] Univ Alabama, Dept Genet, Birmingham, AL USA.
RP Lubet, RA (reprint author), NCI, Canc Prevent Div, Execut Plaza N,Suite 2110,6130 Execut Blvd, Bethesda, MD 20852 USA.
EM lubetr@mail.nih.gov
FU NCI [HHSN261200433001C]
FX The authors wish to thank Jeanne Hale, Mary Jo Cagle, and Julie Gray for
their secretarial and editorial services. Research materials for the
studies were in part obtained by the NCI contract number
HHSN261200433001C.
NR 28
TC 4
Z9 4
U1 4
U2 8
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD MAY
PY 2012
VL 27
IS 5
BP 1400
EP 1406
DI 10.3892/or.2012.1673
PG 7
WC Oncology
SC Oncology
GA 917TX
UT WOS:000302202600016
PM 22307264
ER
PT J
AU Wang, XY
Chrysovergis, K
Bienstock, RJ
Shim, M
Eling, TE
AF Wang, Xingya
Chrysovergis, Kali
Bienstock, Rachelle J.
Shim, Minsub
Eling, Thomas E.
TI The H6D variant of NAG-1/GDF15 inhibits prostate xenograft growth in
vivo
SO PROSTATE
LA English
DT Article
DE NAG-1; GDF15; H6D; prostate cancer
ID BETA SUPERFAMILY MEMBER; CANCER CELLS; CRYSTAL-STRUCTURE;
BINDING-SPECIFICITY; TRANSGENIC MICE; CYCLIN D1; IGF-I; CYTOKINE-1;
INSULIN; PROTEIN
AB BACKGROUND Non-steroidal anti-inflammatory drug-activated gene (NAG-1), a divergent member of the transforming growth factor-beta superfamily, has been implicated in many cellular processes, including inflammation, early bone formation, apoptosis, and tumorigenesis. Recent clinical studies suggests that a C to G single nucleotide polymorphism at position 6 (histidine to aspartic acid substitution, or H6D) of the NAG-1 protein is associated with lower human prostate cancer incidence. The objective of the current study is to investigate the activity of NAG-1 H6D variant in prostate cancer tumorigenesis in vivo.
METHODS. Human prostate cancer DU145 cells expressing the H6D NAG-1 or wild-type (WT) NAG-1 were injected subcutaneously into nude mice and tumor growth was monitored. Serum and tumor samples were collected for subsequent analysis.
RESULTS. The H6D variant was more potent than the WT NAG-1 and inhibited tumor growth significantly compared to control mice. Mice with tumors expressing the WT NAG-1 have greater reduced both body weight and abdominal fat than mice with H6D variant tumors suggesting different activities of the WT NAG-1 and the H6D NAG-1. A significant reduction in adiponectin, leptin, and IGF-1 serum levels was observed in the tumor-bearing mice with a more profound reduction observed with expression of H6D variant. Cyclin D1 expression was suppressed in the tumors with a dramatic reduction observed in the tumor expressing the H6D variant.
CONCLUSION. Our data suggest that the H6D variant of NAG-1 inhibits prostate tumorigenesis by suppressing IGF-1 and cyclin D1 expression but likely additional mechanisms are operative. Prostate 72:677-689, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Wang, Xingya; Chrysovergis, Kali; Shim, Minsub; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Bienstock, Rachelle J.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM eling@niehs.nih.gov
OI Bienstock, Rachelle/0000-0001-5228-3610
FU NIH; National Institute of Environmental Health Sciences
FX Grant sponsor: Intramural Research Program of the NIH; Grant sponsor:
National Institute of Environmental Health Sciences.
NR 50
TC 7
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY
PY 2012
VL 72
IS 6
BP 677
EP 689
DI 10.1002/pros.21471
PG 13
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 911JG
UT WOS:000301712500011
PM 21809352
ER
PT J
AU Lee, YC
Chen, DY
Dodd, SJ
Bouraoud, N
Koretsky, AP
Krishnan, KM
AF Lee, Yi-Cheng
Chen, Der-Yow
Dodd, Stephen J.
Bouraoud, Nadia
Koretsky, Alan P.
Krishnan, Kannan M.
TI The Use of Silica Coated MnO Nanoparticles to Control MRI Relaxivity in
Response to Specific Physiological Changes
SO BIOMATERIALS
LA English
DT Article
DE Manganese enhanced MRI; MnO nanoparticle; Contrast agent; pH-responsive
ID MAGNETIC-RELAXATION SWITCH; RESONANCE-IMAGING MEMRI; CELLULAR MRI;
AGENT; ACTIVATION; SPIN
AB MnO nanoparticles have been tested to engineer a delayed increase in MRI T-1 relaxivity caused by cellular uptake via endocytosis into acidic compartments. Various coatings on core-shell structured MnO nanoparticles were tested for those that had the lowest T-1 relaxivity at pH 7.4, a pH where MnO does not dissolve into Mn2+ ions. The rate of dissolution and release of Mn2+ of the different coated MnO particles as well as changes in T-1 relaxivity were measured at pH 5, a pH routinely obtained in the endosomal-lysosomal pathway. Of a number of coatings, silica coated MnO (MnO@SiO2) had the lowest relaxivity at pH 7.4 (0.29 mM(-1) sec(-1)). About one third of the MnO dissolved within 20 min and the T-1 relaxivity increased to that of free Mn2+ (6.10 mM(-1) sec(-1)) after three days at pH 5. MRI of MnO@SiO2 particles injected into the rat brain showed time-dependent signal changes consistent with the in vitro rates. Thalamocortical tract-tracing could be observed due to the released Mn2+. Intravenous infusion of MnO@SiO2 particles showed little enhancement in any tissue except gallbladder. The gallbladder enhancement was interpreted to be due to endocytosis by liver cells and excretion of Mn2+ ions into the gallbladder. The MnO@SiO2 core-shell nanoparticles show the best potential for delaying the release of miti contrast until endocytosis into low pH compartments activate MRI contrast. The delayed enhancement may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be recycled by endocytosis. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Lee, Yi-Cheng; Krishnan, Kannan M.] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Chen, Der-Yow; Dodd, Stephen J.; Bouraoud, Nadia; Koretsky, Alan P.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Krishnan, KM (reprint author), Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
EM KoretskyA@ninds.nih.gov; kannanmk@uw.edu
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NINDS; NIH
FX The authors would like to acknowledge expertise of Ms. Kathryn Sharer.
This research was supported by the Intramural Research Program of the
NINDS, NIH.
NR 27
TC 30
Z9 30
U1 9
U2 67
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 MAY
PY 2012
VL 33
IS 13
BP 3560
EP 3567
DI 10.1016/j.biomaterials.2012.01.062
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 913XD
UT WOS:000301909800006
PM 22341582
ER
PT J
AU Groppa, S
Oliviero, A
Eisen, A
Quartarone, A
Cohen, LG
Mall, V
Kaelin-Lang, A
Mima, T
Rossi, S
Thickbroom, GW
Rossini, PM
Ziemann, U
Valls-Sole, J
Siebner, HR
AF Groppa, S.
Oliviero, A.
Eisen, A.
Quartarone, A.
Cohen, L. G.
Mall, V.
Kaelin-Lang, A.
Mima, T.
Rossi, S.
Thickbroom, G. W.
Rossini, P. M.
Ziemann, U.
Valls-Sole, J.
Siebner, H. R.
TI A practical guide to diagnostic transcranial magnetic stimulation:
Report of an IFCN committee
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Transcranial magnetic stimulation; Clinical neurophysiology;
Corticomotor conduction; Motor-evoked potentials
ID MOTOR EVOKED-POTENTIALS; INFLAMMATORY DEMYELINATING POLYNEUROPATHY;
CENTRAL-NERVOUS-SYSTEM; SILENT PERIOD; BRAIN-STIMULATION;
MULTIPLE-SCLEROSIS; CONSCIOUS HUMANS; CEREBRAL-CORTEX; NORMAL VALUES;
INTERHEMISPHERIC DIFFERENCES
AB Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Siebner, H. R.] Copenhagen Univ Hosp Hvidovre, DRCMR, DK-2650 Hvidovre, Denmark.
[Groppa, S.] Univ Kiel, Dept Neurol, D-2300 Kiel, Germany.
[Oliviero, A.] Hosp Nacl Paraplej, Toledo, Spain.
[Eisen, A.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada.
[Quartarone, A.] Univ Messina, Dept Neurosci Psychiat & Anesthesiol, Messina, Italy.
[Cohen, L. G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD USA.
[Mall, V.] Univ Freiburg, Dept Neuropediat & Muscle Disorders, D-79106 Freiburg, Germany.
[Kaelin-Lang, A.] Univ Bern, Inselspital, Dept Neurol, CH-3010 Bern, Switzerland.
[Mima, T.] Univ Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan.
[Rossi, S.] Univ Siena, Dipartimento Neurosci, Sez Neurol & Neurofisiol Clin, Policlin Le Scotte, I-53100 Siena, Italy.
[Thickbroom, G. W.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia.
[Rossini, P. M.] Catholic Univ, Inst Neurol, Pol Gemelli, Italy.
[Rossini, P. M.] IRCCS S Raffaele Pisana & Casa Cura S Raffaele Ca, Rome, Italy.
[Ziemann, U.] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany.
[Valls-Sole, J.] Univ Barcelona, Hosp Clin, Serv Neurol, Unitat EMG, E-08007 Barcelona, Spain.
RP Siebner, HR (reprint author), Copenhagen Univ Hosp Hvidovre, DRCMR, Kettegards Alle 30, DK-2650 Hvidovre, Denmark.
EM hartwig.siebner@drcmr.dk
RI Rossini, Paolo /D-4994-2013; Groppa, Sergiu/G-4606-2014; Siebner,
Hartwig/G-4052-2016;
OI Rossini, Paolo /0000-0003-2665-534X; QUARTARONE,
Angelo/0000-0003-1485-6590; Mima, Tatsuya/0000-0001-7787-4855; rossi,
simone/0000-0001-6697-9459
FU Intramural NIH HHS [ZIA NS002978-12]
NR 131
TC 192
Z9 195
U1 7
U2 54
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 MAY
PY 2012
VL 123
IS 5
BP 858
EP 882
DI 10.1016/j.clinph.2012.01.010
PG 25
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 916RS
UT WOS:000302121500007
PM 22349304
ER
PT J
AU Sato, K
Corbett, J
Mason, RP
Kadiiska, MB
AF Sato, Keizo
Corbett, Jean
Mason, Ronald P.
Kadiiska, Maria B.
TI In vivo evidence of free radical generation in the mouse lung after
exposure to Pseudomonas aeruginosa bacterium: An ESR spin-trapping
investigation
SO FREE RADICAL RESEARCH
LA English
DT Article
DE free radicals; mice; Pseudomonas aeruginosa pneumonia; NADPH-oxidase;
xanthine-oxidase
ID ENDOTHELIAL-CELL INJURY; XANTHINE-OXIDASE; LIPID-PEROXIDATION; OXIDATIVE
STRESS; GENE-EXPRESSION; NADPH OXIDASE; HOST-DEFENSE; NITRIC-OXIDE;
DESFERRIOXAMINE; RESONANCE
AB In the Pseudomonas aeruginosa-induced rodent pneumonia model, it is thought that free radicals are significantly associated with the disease pathogenesis. However, until now there has been no direct evidence of free radical generation in vivo. Here we used electron spin resonance (ESR) and in vivo spin trapping with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone to investigate free radical production in a murine model. We detected and identified generation of lipid-derived free radicals in vivo (a(N) = 14.86 +/- 0.03 G and a(H)beta = 2.48 +/- 0.09 G). To further investigate the mechanism of lipid radical production, we used modulating agents and knockout mice. We found that with GdCl3 (phagocytic toxicant), NADPH-oxidase knockout mice (Nox2(-/-)), allopurinol (xanthine-oxidase inhibitor) and Desferal (metal chelator), generation of lipid radicals was decreased; histopathological and biological markers of acute lung injury were noticeably improved. Our study demonstrates that lipid-derived free radical formation is mediated by NADPH-oxidase and xanthine-oxidase activation and that metal-catalysed hydroxyl radical-like species play important roles in lung injury caused by Pseudomonas aeruginosa.
C1 [Corbett, Jean; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Sato, Keizo] Kyushu Univ Hlth & Welf, Sch Pharmaceut Sci, Dept Biochem 1, Nobeoka, Japan.
RP Kadiiska, MB (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM kadiiska@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01 ES0501 39-13]
FX The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper. This research was
supported by the Intramural Research Program of the National Institutes
of Health and by the National Institute of Environmental Health Sciences
Grant Z01 ES0501 39-13.
NR 55
TC 2
Z9 2
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1071-5762
J9 FREE RADICAL RES
JI Free Radic. Res.
PD MAY
PY 2012
VL 46
IS 5
BP 645
EP 655
DI 10.3109/10715762.2012.667089
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 915KR
UT WOS:000302024100007
PM 22339444
ER
PT J
AU Abnet, CC
Wang, ZM
Song, X
Hu, N
Zhou, FY
Freedman, ND
Li, XM
Yu, K
Shu, XO
Yuan, JM
Zheng, W
Dawsey, SM
Liao, LM
Lee, MP
Ding, T
Qiao, YL
Gao, YT
Koh, WP
Xiang, YB
Tang, ZZ
Fan, JH
Chung, CC
Wang, CY
Wheeler, W
Yeager, M
Yuenger, J
Hutchinson, A
Jacobs, KB
Giffen, CA
Burdett, L
Fraumeni, JF
Tucker, MA
Chow, WH
Zhao, XK
Li, JM
Li, AL
Sun, LD
Wei, W
Li, JL
Zhang, P
Li, HL
Cui, WY
Wang, WP
Liu, ZC
Yang, X
Fu, WJ
Cui, JL
Lin, HL
Zhu, WL
Liu, M
Chen, X
Chen, J
Guo, L
Han, JJ
Zhou, SL
Huang, J
Wu, Y
Yuan, C
Huang, J
Ji, AF
Kul, JW
Fan, ZM
Wang, JP
Zhang, DY
Zhang, LQ
Zhang, W
Chen, YF
Ren, JL
Li, XM
Dong, JC
Xing, GL
Guo, ZG
Yang, JX
Mao, YM
Yuan, Y
Guo, ET
Zhang, W
Hou, ZC
Liu, J
Li, Y
Tang, S
Chang, J
Peng, XQ
Han, M
Yin, WL
Liu, YL
Hu, YL
Liu, Y
Yang, LQ
Zhu, FG
Yang, XF
Feng, XS
Wang, Z
Li, Y
Gao, SG
Liu, HL
Yuan, L
Jin, Y
Zhang, YR
Sheyhidin, I
Li, F
Chen, BP
Ren, SW
Liu, B
Li, D
Zhang, GF
Yue, WB
Feng, CW
Qige, QRW
Zhao, JT
Yang, WJ
Lei, GY
Chen, LQ
Li, EM
Xu, LY
Wu, ZY
Bao, ZQ
Chen, JL
Li, XC
Zhuang, X
Zhou, YF
Zuo, XB
Dong, ZM
Wang, LW
Fan, XP
Wang, J
Zhou, Q
Ma, GS
Zhang, QX
Liu, H
Jian, XY
Lian, SY
Wang, JS
Chang, FB
Lu, CD
Miao, JJ
Chen, ZG
Wang, R
Guo, M
Fan, ZL
Tao, P
Liu, TJ
Wei, JC
Kong, QP
Fan, L
Wang, XZ
Gao, FS
Wang, TY
Xie, D
Wang, L
Chen, SQ
Yang, WC
Hong, JY
Wang, L
Qiu, SL
Goldstein, AM
Yuan, ZQ
Chanock, SJ
Zhang, XJ
Taylor, PR
Wang, LD
AF Abnet, Christian C.
Wang, Zhaoming
Song, Xin
Hu, Nan
Zhou, Fu-You
Freedman, Neal D.
Li, Xue-Min
Yu, Kai
Shu, Xiao-Ou
Yuan, Jian-Min
Zheng, Wei
Dawsey, Sanford M.
Liao, Linda M.
Lee, Maxwell P.
Ding, Ti
Qiao, You-Lin
Gao, Yu-Tang
Koh, Woon-Puay
Xiang, Yong-Bing
Tang, Ze-Zhong
Fan, Jin-Hu
Chung, Charles C.
Wang, Chaoyu
Wheeler, William
Yeager, Meredith
Yuenger, Jeff
Hutchinson, Amy
Jacobs, Kevin B.
Giffen, Carol A.
Burdett, Laurie
Fraumeni, Joseph F., Jr.
Tucker, Margaret A.
Chow, Wong-Ho
Zhao, Xue-Ke
Li, Jiang-Man
Li, Ai-Li
Sun, Liang-Dan
Wei, Wu
Li, Ji-Lin
Zhang, Peng
Li, Hong-Lei
Cui, Wen-Yan
Wang, Wei-Peng
Liu, Zhi-Cai
Yang, Xia
Fu, Wen-Jing
Cui, Ji-Li
Lin, Hong-Li
Zhu, Wen-Liang
Liu, Min
Chen, Xi
Chen, Jie
Guo, Li
Han, Jing-Jing
Zhou, Sheng-Li
Huang, Jia
Wu, Yue
Yuan, Chao
Huang, Jing
Ji, Ai-Fang
Kul, Jian-Wei
Fan, Zhong-Min
Wang, Jian-Po
Zhang, Dong-Yun
Zhang, Lian-Qun
Zhang, Wei
Chen, Yuan-Fang
Ren, Jing-Li
Li, Xiu-Min
Dong, Jin-Cheng
Xing, Guo-Lan
Guo, Zhi-Gang
Yang, Jian-Xue
Mao, Yi-Ming
Yuan, Yuan
Guo, Er-Tao
Zhang, Wei
Hou, Zhi-Chao
Liu, Jing
Li, Yan
Tang, Sa
Chang, Jia
Peng, Xiu-Qin
Han, Min
Yin, Wan-Li
Liu, Ya-Li
Hu, Yan-Long
Liu, Yu
Yang, Liu-Qin
Zhu, Fu-Guo
Yang, Xiu-Feng
Feng, Xiao-Shan
Wang, Zhou
Li, Yin
Gao, She-Gan
Liu, Hai-Lin
Yuan, Ling
Jin, Yan
Zhang, Yan-Rui
Sheyhidin, Ilyar
Li, Feng
Chen, Bao-Ping
Ren, Shu-Wei
Liu, Bin
Li, Dan
Zhang, Gao-Fu
Yue, Wen-Bin
Feng, Chang-Wei
Qige, Qirenwang
Zhao, Jian-Ting
Yang, Wen-Jun
Lei, Guang-Yan
Chen, Long-Qi
Li, En-Min
Xu, Li-Yan
Wu, Zhi-Yong
Bao, Zhi-Qin
Chen, Ji-Li
Li, Xian-Chang
Zhuang, Xiang
Zhou, Ying-Fa
Zuo, Xian-Bo
Dong, Zi-Ming
Wang, Lu-Wen
Fan, Xue-Pin
Wang, Jin
Zhou, Qi
Ma, Guo-Shun
Zhang, Qin-Xian
Liu, Hai
Jian, Xin-Ying
Lian, Sin-Yong
Wang, Jin-Sheng
Chang, Fu-Bao
Lu, Chang-Dong
Miao, Jian-Jun
Chen, Zhi-Guo
Wang, Ran
Guo, Ming
Fan, Zeng-Lin
Tao, Ping
Liu, Tai-Jing
Wei, Jin-Chang
Kong, Qing-Peng
Fan, Lei
Wang, Xian-Zeng
Gao, Fu-Sheng
Wang, Tian-Yun
Xie, Dong
Wang, Li
Chen, Shu-Qing
Yang, Wan-Cai
Hong, Jun-Yan
Wang, Liang
Qiu, Song-Liang
Goldstein, Alisa M.
Yuan, Zhi-Qing
Chanock, Stephen J.
Zhang, Xue-Jun
Taylor, Philip R.
Wang, Li-Dong
TI Genotypic variants at 2q33 and risk of esophageal squamous cell
carcinoma in China: a meta-analysis of genome-wide association studies
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SUSCEPTIBILITY LOCI; CASP8 PROMOTER; CANCER-RISK; PLCE1; GENE;
ADENOCARCINOMA; POLYMORPHISMS; CASPASE-8; COMMON
AB Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P 5 10(8), and the strongest signal was rs13016963, with a combined odds ratio (95 confidence interval) of 1.29 (1.191.40) and P 7.63 10(10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
C1 [Abnet, Christian C.] NCI, Nutr Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA.
[Lee, Maxwell P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Chung, Charles C.; Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Jacobs, Kevin B.; Burdett, Laurie] SAIC Frederick, Core Genotyping Facil, NCI Frederick, Frederick, MD USA.
[Song, Xin; Zhao, Xue-Ke; Li, Jiang-Man; Li, Ai-Li; Zhang, Peng; Cui, Wen-Yan; Cui, Ji-Li; Lin, Hong-Li; Li, Xiu-Min; Guo, Zhi-Gang; Liu, Ya-Li; Hu, Yan-Long; Liu, Hai-Lin; Jin, Yan; Chen, Zhi-Guo; Wang, Tian-Yun; Yang, Wan-Cai; Yuan, Zhi-Qing; Wang, Li-Dong] Xinxiang Med Univ, Canc Res Ctr, Xinxiang 453003, Henan, Peoples R China.
[Song, Xin; Zhao, Xue-Ke; Li, Jiang-Man; Li, Hong-Lei; Wang, Wei-Peng; Liu, Zhi-Cai; Yang, Xia; Fu, Wen-Jing; Zhu, Wen-Liang; Liu, Min; Chen, Xi; Chen, Jie; Guo, Li; Han, Jing-Jing; Zhou, Sheng-Li; Huang, Jia; Wu, Yue; Yuan, Chao; Huang, Jing; Ji, Ai-Fang; Kul, Jian-Wei; Fan, Zhong-Min; Wang, Jian-Po; Zhang, Dong-Yun; Zhang, Lian-Qun; Dong, Jin-Cheng; Xing, Guo-Lan; Yang, Jian-Xue; Mao, Yi-Ming; Yuan, Yuan; Guo, Er-Tao; Zhang, Wei; Hou, Zhi-Chao; Liu, Jing; Li, Yan; Tang, Sa; Chang, Jia; Peng, Xiu-Qin; Yin, Wan-Li; Liu, Yu; Li, Dan; Yue, Wen-Bin; Zhuang, Xiang; Zhou, Ying-Fa; Wang, Lu-Wen; Fan, Xue-Pin; Wang, Jin; Wang, Ran; Guo, Ming; Wang, Li; Qiu, Song-Liang; Wang, Li-Dong] Zhengzhou Univ, Affiliated Hosp 1, Henan Key Lab Esophageal Canc Res, Zhengzhou 450052, Henan, Peoples R China.
[Ren, Jing-Li; Feng, Chang-Wei] Zhengzhou Univ, Affiliated Hosp 2, Dept Basic Oncol & Pathol, Zhengzhou 450052, Henan, Peoples R China.
[Zhou, Fu-You; Wang, Jian-Po; Zhang, Lian-Qun; Lu, Chang-Dong] Anyang Tumor Hosp, Dept Thorac Surg & Tumor Prevent Treatment, Anyang 455000, Henan, Peoples R China.
[Li, Xue-Min; Bao, Zhi-Qin; Chen, Ji-Li; Miao, Jian-Jun; Fan, Zeng-Lin; Fan, Lei] Cixian Hosp, Dept Pathol & Thorac Surg, Ctr Hlth Screening & Endoscopy, Cixian 056500, Hebei, Peoples R China.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA.
[Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
[Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Dept Epidemiol, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China.
[Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Wheeler, William; Giffen, Carol A.; Li, Xian-Chang] Informat Management Serv Inc, Silver Spring, MD USA.
[Li, Ai-Li; Lian, Sin-Yong] Tumor Hosp Linzhou, Dept Thorac Surg, Linzhou 456550, Henan, Peoples R China.
[Sun, Liang-Dan; Zuo, Xian-Bo; Zhang, Xue-Jun] Anhui Med Univ, Key Lab Dermatol, Minist Educ, Hefei 230032, Anhui, Peoples R China.
[Wei, Wu; Ji, Ai-Fang; Wang, Jin-Sheng] Changzhi Med Univ, Inst Hematol Dis, Changzhi 046000, Shanxi, Peoples R China.
[Wei, Wu; Ji, Ai-Fang; Wang, Jin-Sheng] Changzhi Med Univ, Dept Pathol, Changzhi 046000, Shanxi, Peoples R China.
[Li, Ji-Lin; Jian, Xin-Ying; Wei, Jin-Chang] Linzhou Esophageal Canc Hosp, Dept Pathol & Thorac Surg, Linzhou 456592, Henan, Peoples R China.
[Kul, Jian-Wei] Nanyang Med Coll, Affiliated Hosp 1, Dept Oncol, Nanyang 473058, Henan, Peoples R China.
[Zhang, Wei; Zhao, Jian-Ting] First Peoples Hosp Hebi, Dept Oncol, Hebi 458000, Henan, Peoples R China.
[Chen, Yuan-Fang] Hebi City Publ Hlth Bur, Dept Biostat, Hebi 458000, Henan, Peoples R China.
[Dong, Jin-Cheng] Qixian Commerce Bur, Hebi 456750, Henan, Peoples R China.
[Yang, Jian-Xue; Mao, Yi-Ming; Peng, Xiu-Qin; Feng, Xiao-Shan; Gao, She-Gan] Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Oncol, Luoyang 471003, Henan, Peoples R China.
[Han, Min; Zhu, Fu-Guo] First Peoples Hosp Shangqiu, Dept Gastroenterol & Thorac Surg, Shangqiu 476100, Henan, Peoples R China.
[Yang, Liu-Qin] Xinxiang Cent Hosp, Dept Radiotherapy, Xinxiang 453000, Henan, Peoples R China.
[Yang, Xiu-Feng] Hebi Dahejian Hosp, Dept Surg, Hebi 458000, Henan, Peoples R China.
[Wang, Zhou] Shandong Univ, Prov Hosp, Dept Thorac Surg, Jinan 250021, Shandong, Peoples R China.
[Li, Yin; Yuan, Ling] Zhengzhou Univ, Canc Hosp, Dept Thorac Surg & Radiotherapy, Zhengzhou 450008, Henan, Peoples R China.
[Zhang, Yan-Rui] Zhengzhou Univ, Dept Gastroenterol, Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China.
[Sheyhidin, Ilyar] Xinjiang Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Urumqi 830054, Xinjiang, Peoples R China.
[Sheyhidin, Ilyar] Xinjiang Med Univ, Med Res Ctr, Affiliated Hosp 1, Urumqi 830054, Xinjiang, Peoples R China.
[Li, Feng] Shihezi Univ, Sch Med, Dept Pathol, Shihezi 832002, Xinjiang, Peoples R China.
[Chen, Bao-Ping] Henan Univ, Huaihe Hosp, Dept Nephrol, Kaifeng 475000, Henan, Peoples R China.
[Ren, Shu-Wei] Xinyang Cent Hosp, Dept Oncol, Xinyang 464000, Henan, Peoples R China.
[Liu, Bin; Gao, Fu-Sheng] Capital Med Univ, Beijing Tongren Hosp, Dept Gastroenterol, Beijing 100176, Peoples R China.
[Li, Dan; Zhang, Gao-Fu; Liu, Tai-Jing] Red Cross Hosp Huojia, Dept Surg, Xinxiang 453800, Henan, Peoples R China.
[Yue, Wen-Bin] Puyang City Oil Field Hosp, Dept Oncol, Puyang 457000, Henan, Peoples R China.
[Qige, Qirenwang] Inner Mongolia Med Coll, Affiliated Hosp, Dept Internal Mongolia Med, Hohhot 010050, Inner Mongolia, Peoples R China.
[Yang, Wen-Jun] Ningxia Med Univ, Dept Biotechnol, Yinchuan 750004, Ningxia, Peoples R China.
[Lei, Guang-Yan] Tumor Hosp Shaanxi Prov, Dept Thorac Surg, Xian 710061, Shaanxi, Peoples R China.
[Chen, Long-Qi] Sichuan Univ, Dept Thorac & Cardiovasc Surg, W China Hosp, Chengdu 610041, Sichuan, Peoples R China.
[Li, En-Min; Xu, Li-Yan; Wu, Zhi-Yong] Shantou Univ, Dept Oncol Pathol, Coll Med, Shantou 515041, Guangdong, Peoples R China.
[Li, En-Min; Xu, Li-Yan; Wu, Zhi-Yong] Shantou Univ, Coll Med, Dept Biochem & Mol Biol, Shantou 515041, Guangdong, Peoples R China.
[Dong, Zi-Ming; Zhou, Qi; Zhang, Qin-Xian] Zhengzhou Univ, Basic Med Coll, Dept Pathol & Oncol, Zhengzhou 450052, Henan, Peoples R China.
[Ma, Guo-Shun] Neihuang Publ Hlth Bur, Dept Biostat, Anyang 4563000, Henan, Peoples R China.
[Liu, Hai] Third Peoples Hosp Yunnan Prov, Dept Gastroenterol, Kunming 650011, Yunnan, Peoples R China.
[Chang, Fu-Bao] Chinese Med Hosp Linzhou, Dept Thorac Surg, Linzhou 456550, Henan, Peoples R China.
[Tao, Ping] Langzhongshi Peoples Hosp, Dept Oncol Pathol, Langzhong 637400, Sichuan, Peoples R China.
[Kong, Qing-Peng] Chinese Acad Sci, State Key Lab Genet Resource & Evolut, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China.
[Wang, Xian-Zeng] Linzhou Peoples Hosp, Dept Thorac Surg, Linzhou 456550, Henan, Peoples R China.
[Xie, Dong] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Chen, Shu-Qing; Hong, Jun-Yan] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.
[Wang, Liang] Med Coll Wisconsin, MCW Canc Ctr, Dept Pathol, Milwaukee, WI 53226 USA.
RP Abnet, CC (reprint author), NCI, Nutr Epidemiol Branch, DCEG, NIH, EPS 320, Bethesda, MD 20892 USA.
EM abnetc@mail.nih.gov; ldwang@xxmu.edu.cn
RI Chen, Gang/G-2722-2010; Qiao, You-Lin/B-4139-2012; Tucker,
Margaret/B-4297-2015; Abnet, Christian/C-4111-2015; Freedman,
Neal/B-9741-2015;
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; ren, jingli/0000-0001-9891-0579;
Liao, Linda/0000-0002-1923-5294; Chen, Shuqing/0000-0002-0792-3735;
Yuan, Jian-Min/0000-0002-4620-3108
FU Xinxiang Medical University [2009-5]; National Natural Science
Foundations of China [30670956, 30971133]; 863 HighTech Key Projects
[2006AA02A403, 2007AA02Z161]; China Key Program on Basic Research
[2007CB516812]; Science and Technology Department [2009-8]; Health
Department [2009-10]; Education Department of Henan Province [2008-7];
Anhui Provincial Special Scientific Program [2007-7]; National Cancer
Institute [R01 CA82729, R37 CA70837, NO2-CP-11010, R01 CA55069, R35
CA53890, R01 CA80205, R01 CA144034, NO2-SC-66211, NO1-SC-91030,
HHSN261200477001C]; Vanderbilt University; Shanxi Cancer Hospital;
Institute, Taiyuan, Shanxi, China; Cancer Institute of the Chinese
Academy of Medical Sciences, Beijing, China; NIH, National Cancer
Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by the Xinxiang Medical University Key
Scientific Program (2009-5), the National Natural Science Foundations of
China (30670956, 30971133), 863 HighTech Key Projects (2006AA02A403,
2007AA02Z161), China Key Program on Basic Research (2007CB516812),
Special Scientific Programs from Science and Technology Department
(2009-8), Health Department (2009-10) and Education Department (2008-7)
of Henan Province and the Anhui Provincial Special Scientific Program
(2007-7). The Shanghai Men's Health Study (SMHS) was supported by the
National Cancer Institute extramural research grant (R01 CA82729). The
Shanghai Women's Health Study (SWHS) was supported by the National
Cancer Institute extramural research grant (R37 CA70837) and, partially
for biological sample collection, National Cancer Institute Intramural
Research Program contract NO2-CP-11010 with Vanderbilt University. The
Singapore Chinese Health Study (SCHS) was supported by the National
Cancer Institute extramural research grants (R01 CA55069, R35 CA53890,
R01 CA80205 and R01 CA144034). The Shanxi Upper Gastrointestinal Cancer
Genetics Project was supported by the National Cancer Institute
Intramural Research Program contract NO2-SC-66211 with the Shanxi Cancer
Hospital and Institute, Taiyuan, Shanxi, China. The Nutrition
Intervention Trials (NIT) were supported by National Cancer Institute
Intramural Research Program contracts NO1-SC-91030 and HHSN261200477001C
with the Cancer Institute of the Chinese Academy of Medical Sciences,
Beijing, China. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics.
NR 34
TC 25
Z9 27
U1 2
U2 45
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2012
VL 21
IS 9
BP 2132
EP 2141
DI 10.1093/hmg/dds029
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 919DU
UT WOS:000302302800018
PM 22323360
ER
PT J
AU Zwingenberger, AL
Vernau, W
Shi, CY
Yan, WS
Chen, XB
Gordon, IK
Kent, MS
AF Zwingenberger, Allison L.
Vernau, William
Shi, Changying
Yan, Wensheng
Chen, Xinbin
Gordon, Ira K.
Kent, Michael S.
TI Development and characterization of 5 canine B-cell lymphoma cell lines
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Canine; B-cell lymphoma; Cell line; Non-Hodgkin's
ID DNA-DAMAGE; MDM2; P53; MODELS; CANCER; DEGRADATION; CLEAVAGE; MASKING
AB Canine and human lymphoma share similar characteristics in disease development and response to therapy. Translational research can be furthered using tools such as canine cell lines to model therapeutic compounds and strategies. We developed 5 B-cell lymphoma cell lines from dogs with confirmed large B-cell lymphoma. These cell lines were CD3, CD18, CD20, and CD90 positive with variable CD79a, CD1c and CD34 expression. All cell lines were tumorigenic in Nu/nu mice and were wild type for p53. Canine lymphoma cell lines serve as an important resource for translational lymphoma research. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Zwingenberger, Allison L.; Shi, Changying; Yan, Wensheng; Chen, Xinbin; Kent, Michael S.] Univ Calif Davis, Dept Surg & Radiol Sci, Sch Vet Med, Davis, CA 95616 USA.
[Vernau, William] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Gordon, Ira K.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Zwingenberger, AL (reprint author), Univ Calif Davis, Dept Surg & Radiol Sci, Sch Vet Med, 1 Shields Ave, Davis, CA 95616 USA.
EM azwingen@ucdavis.edu
RI perumal, murugiah/D-1565-2012;
OI /0000-0002-8982-2558
FU Toni Wiebe Memorial Research Fund; UCD Cancer Center [NIH CA093373]
FX Toni Wiebe Memorial Research Fund and the UCD Cancer Center Core Support
Grant NIH CA093373. The above sponsors had no involvement in study
design, data collection, analysis, interpretation of data, writing of
the manuscript, or the decision to submit the manuscript for
publication.
NR 23
TC 3
Z9 3
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD MAY
PY 2012
VL 36
IS 5
BP 601
EP 606
DI 10.1016/j.leukres.2011.11.004
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 916QB
UT WOS:000302117200024
PM 22136758
ER
PT J
AU Vosters, JL
Roescher, N
Illei, GG
Chiorini, JA
Tak, PP
AF Vosters, J. L.
Roescher, N.
Illei, G. G.
Chiorini, J. A.
Tak, P. P.
TI TACI-Fc gene therapy improves autoimmune sialadenitis but not salivary
gland function in non-obese diabetic mice
SO ORAL DISEASES
LA English
DT Article
DE TACI-Fc; gene therapy; salivary gland; non-obese diabetic mice;
Sjogren's syndrome
ID PRIMARY SJOGRENS-SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR
FAMILY; MEMORY B-CELLS; RHEUMATOID-ARTHRITIS; TNF RECEPTOR; AUTOANTIBODY
PRODUCTION; CONTROLLED-TRIAL; IMAGE-ANALYSIS; MEMBERS APRIL
AB OBJECTIVE: Patients with Sjogren's syndrome (SS) show aberrant expression of the B cell-related mediators, B cell-activating factor (BAFF), and a proliferationinducing ligand (APRIL) in serum and salivary glands (SGs). We studied the biological effect of neutralizing these cytokines by local gene transfer of the common receptor transmembrane activator and CAML interactor (TACI) in an animal model of SS.
MATERIAL AND METHODS: A recombinant serotype 2 adeno-associated virus (rAAV2) encoding TACI-Fc was constructed, and its efficacy was tested in the SGs of nonobese diabetic mice. Ten weeks later, SG inflammation was evaluated and serum and SG tissue were analyzed for inflammatory markers including immunoglobulins (Ig) and cytokines.
RESULTS: AAV2-TACI-Fc gene therapy significantly reduced the number of inflammatory foci in the SG, owing to a decrease in IgD(+) cells and CD138(+) cells. Moreover, IgG and IgM levels, but not IgA levels, were reduced in the SG. Overall expression of mainly proinflammatory cytokines tended to be lower in AAV2-TACIFc- treated mice. Salivary flow was unaffected.
CONCLUSION: Although local expression of soluble TACI-Fc reduced inflammation and immunoglobulin levels in the SG, further research will have to prove whether dual blockade of APRIL and BAFF by TACI-Fc can provide a satisfying treatment for the clinical symptoms of patients. Oral Diseases (2012) 18, 365-374
C1 [Vosters, J. L.; Roescher, N.; Tak, P. P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands.
[Vosters, J. L.; Roescher, N.; Illei, G. G.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Vosters, JL (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, F4-105,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM j.l.vosters@amc.uva.nl
FU Dutch Arthritis Association [NR 07-1-406]; National Institutes of Health
(NIH), National Institute of Dental and Craniofacial Research (NIDCR)
FX The authors thank the NIH Fellows Editorial Board for critical review of
this manuscript and Scott A. Loiler (Arthrogen B. V., the Netherlands)
for designing the primers for TACI-ED construction. This work is
supported by a Dutch Arthritis Association grant [NR 07-1-406] to JLV
and National Institutes of Health (NIH), National Institute of Dental
and Craniofacial Research (NIDCR) intramural research grant to JAC and
NR. The authors declare no conflict of interest.
NR 56
TC 11
Z9 12
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD MAY
PY 2012
VL 18
IS 4
BP 365
EP 374
DI 10.1111/j.1601-0825.2011.01885.x
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 915DK
UT WOS:000302003800006
PM 22212434
ER
PT J
AU Doroshow, JH
Juhasz, A
Ge, Y
Holbeck, S
Lu, JM
Antony, S
Wu, YZ
Jiang, GJ
Roy, K
AF Doroshow, James H.
Juhasz, Agnes
Ge, Yun
Holbeck, Susan
Lu, Jiamo
Antony, Smitha
Wu, Yongzhong
Jiang, Guojian
Roy, Krishnendu
TI Antiproliferative mechanisms of action of the flavin dehydrogenase
inhibitors diphenylene iodonium and di-2-thienyliodonium based on
molecular profiling of the NCI-60 human tumor cell panel
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Diphenylene iodonium; Dithienyliodonium; Reactive oxygen; Stat
signaling; NADPH oxidase; NCI-60 tumor panel
ID INTESTINAL EPITHELIAL-CELLS; ACTIVATED PROTEIN-KINASE; JAK-STAT PATHWAY;
NADPH OXIDASE; CYCLE PROGRESSION; HYDROGEN-PEROXIDE; REDOX REGULATION;
GENE-EXPRESSION; CANCER-CELLS; MUSCLE CELLS
AB Flavoprotein-dependent reactive oxygen species (ROS) play a critical role in cytokine-mediated signal transduction in normal tissues and tumor cells. The flavoenzyme inhibitors diphenylene iodonium (DPI) and di-2-thienyliodonium (DTI) have been used to inhibit membrane-bound, flavoprotein-containing NADPH oxidases, including epithelial and leukocyte NADPH oxidases (Nox1-5 and Duox 1 and 2). Recent evidence suggests that DPI can decrease tumor cell proliferation; however, the molecular mechanisms involved remain poorly defined. To explore the mechanisms underlying DPI- and DTI-related tumor cell growth delay, we examined growth inhibition patterns produced by both agents in the NCI-60 tumor panel, and determined expression levels of Nox gene family members across these cell lines. Possible molecular targets were predicted using the COMPARE program. DPI was more potent than DTI (GI(50): 10 nM versus 10 mu M); DPI and DTI exposure produced unique patterns of growth inhibition when evaluated against the small molecule anticancer database of the National Cancer Institute. Growth inhibition profiling of DPI revealed a modest positive correlation with Nox1 levels; novel mechanisms of DPI and DTI action, including alterations in Stat, Erk1/2, and Akt pathways, were inferred by correlation with NCI-60 Affymetrix (R) array data. Exposure of HT-29 colon cancer cells, which express Nox1, to DPI and DTI confirmed their inhibitory effects on steady state ROS levels, and demonstrated decreased Stat, Erk1/2, and Akt signaling mediated by IL-4, IL-6, IL-13, and IL-22, possibly due to a concomitant increase in tumor cell phosphatase activity. These findings suggest that DPI and DTI may act therapeutically by altering ROS-related signal transduction. Published by Elsevier Inc.
C1 [Doroshow, James H.; Holbeck, Susan; Roy, Krishnendu] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Doroshow, James H.; Juhasz, Agnes; Ge, Yun; Lu, Jiamo; Antony, Smitha; Wu, Yongzhong; Jiang, Guojian] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov; juhasza@mail.nih.gov; Yun.Ge@fda.hhs.gov;
holbecks@mail.nih.gov; lujiamo@mail.nih.gov; antonys@mail.nih.gov;
wuy@mail.nih.gov; gjiang@mail.nih.gov; royk@navmed.nci.nih.gov
FU Center for Cancer Research; Division of Cancer Treatment and Diagnosis,
National Cancer Institute, National Institutes of Health
FX This work was supported in whole or in part with federal funds from the
Center for Cancer Research and the Division of Cancer Treatment and
Diagnosis, National Cancer Institute, National Institutes of Health. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government.
NR 51
TC 12
Z9 13
U1 0
U2 3
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 MAY 1
PY 2012
VL 83
IS 9
SI SI
BP 1195
EP 1207
DI 10.1016/j.bcp.2012.01.022
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 913WA
UT WOS:000301906900007
PM 22305747
ER
PT J
AU Lai, CY
Tian, LL
Schisterman, EF
AF Lai, Chin-Ying
Tian, Lili
Schisterman, Enrique F.
TI Exact confidence interval estimation for the Youden index and its
corresponding optimal cut-point
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
DE Confidence interval; ROC curve; Sensitivity and specificity; Youden
index; Optimal cut-point; Generalized pivotal quantity
ID GENERALIZED VARIABLE METHOD; NORMAL-POPULATIONS; ROC CURVES;
CORRELATION-COEFFICIENT; PAIRED AREAS; INFERENCES
AB In diagnostic studies, the receiver operating characteristic (ROC) curve and the area under the ROC curve are important tools in assessing the utility of biomarkers in discriminating between non-diseased and diseased populations. For classifying a patient into the non-diseased or diseased group, an optimal cut-point of a continuous biomarker is desirable. Youden's index (J), defined as the maximum vertical distance between the ROC curve and the diagonal line, serves as another global measure of overall diagnostic accuracy and can be used in choosing an optimal cut-point. The proposed approach is to make use of a generalized approach to estimate the confidence intervals of the Youden index and its corresponding optimal cut-point. Simulation results are provided for comparing the coverage probabilities of the confidence intervals based on the proposed method with those based on the large sample method and the parametric bootstrap method. Finally, the proposed method is illustrated via an application to a data set from a study on Duchenne muscular dystrophy (DMD). (C) 2010 Elsevier B.V. All rights reserved.
C1 [Lai, Chin-Ying; Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
[Schisterman, Enrique F.] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA.
RP Lai, CY (reprint author), SUNY Buffalo, Dept Biostat, 249 Farber Hall,3435 Main St,Bldg 26, Buffalo, NY 14214 USA.
EM clai2@buffalo.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU Intramural NIH HHS [Z01 HD008761-05]
NR 20
TC 17
Z9 17
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD MAY 1
PY 2012
VL 56
IS 5
SI SI
BP 1103
EP 1114
DI 10.1016/j.csda.2010.11.023
PG 12
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 910ZW
UT WOS:000301688100011
PM 27099407
ER
PT J
AU McCoy, MK
Cookson, MR
AF McCoy, Melissa K.
Cookson, Mark R.
TI Mitochondrial Quality Control and Dynamics in Parkinson's Disease
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID DROSOPHILA DJ-1 MUTANTS; DOMINANT OPTIC ATROPHY; INDUCED CELL-DEATH;
DOPAMINERGIC-NEURONS; OXIDATIVE STRESS; ALPHA-SYNUCLEIN;
PINK1/PARKIN-MEDIATED MITOPHAGY; SPORADIC PARKINSONS; MEDIATED
AUTOPHAGY; RESPIRATORY-CHAIN
AB Significance: Studies of sporadic cases, toxin models, and genetic causes of Parkinson's disease suggest that mitochondrial dysfunction may be an early feature of pathogenesis. Recent Advances: Compelling evidence of a causal relationship between mitochondrial function and disease was found with the identification of several genes for recessive parkinsonism, PINK1, DJ-1, and parkin. There is evidence that each of these regulates responses to cellular stresses, including oxidative stress and depolarization of the mitochondrial membrane. Specifically, PINK1 and parkin modulate mitochondrial dynamics by promoting autophagic removal of depolarized mitochondria. Mutations in all genes linked to Parkinson's disease lead to enhanced sensitivity to mitochondrial toxins and oxidative stress. Critical Issues: Both increased mitochondrial damage due to complex 1 inhibition, mishandling of calcium, oxidant stress, or impaired clearance of dysfunctional mitochondria would lead to the accumulation of nonfunctional organelles and could contribute to neuronal dysfunction. However, several unanswered questions remain about the underlying mechanism(s) involved. Future Directions: PINK1 and parkin have been demonstrated to regulate mitochondrial dynamics, but the pathways linking PINK1 activity to parkin function are still unclear and warrant further investigation. Antioxid. Redox Signal. 16, 869-882.
C1 [McCoy, Melissa K.; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 115
TC 36
Z9 36
U1 2
U2 18
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 MAY
PY 2012
VL 16
IS 9
BP 869
EP 882
DI 10.1089/ars.2011.4019
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 904VC
UT WOS:000301225200002
PM 21568830
ER
PT J
AU Stewart, DR
Pemov, A
Van Loo, P
Beert, E
Brems, H
Sciot, R
Claes, K
Pak, E
Dutra, A
Lee, CCR
Legius, E
AF Stewart, Douglas R.
Pemov, Alexander
Van Loo, Peter
Beert, Eline
Brems, Hilde
Sciot, Raf
Claes, Kathleen
Pak, Evgenia
Dutra, Amalia
Lee, Chyi-Chia Richard
Legius, Eric
TI Mitotic recombination of chromosome arm 17q as a cause of loss of
heterozygosity of NF1 in neurofibromatosis type 1-associated glomus
tumors
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID NERVE SHEATH TUMORS; ISOCHROMOSOME 17Q; GENE; INSTABILITY; MECHANISMS;
MUTATIONS; IDENTIFICATION; PATHOGENESIS; ANEUPLOIDY; LEUKEMIA
AB Neurofibromatosis type 1 (NF1) is a common, autosomal dominant, tumor-predisposition syndrome that arises secondary to mutations in NF1. Glomus tumors are painful benign tumors that originate from the glomus body in the fingers and toes due to biallelic inactivation of NF1. We karyotyped cultures from four previously reported and one new glomus tumor and hybridized tumor (and matching germline) DNA on Illumina HumanOmni1-Quad SNP arrays (similar to 1 x 10(6) SNPs). Two tumors displayed evidence of copy-neutral loss of heterozygosity of chromosome arm 17q not observed in the germline sample, consistent with a mitotic recombination event. One of these two tumors, NF1-G12, featured extreme polyploidy (near-tetraploidy, near-hexaploidy, or near-septaploidy) across all chromosomes. In the remaining four tumors, there were few cytogenetic abnormalities observed, and copy-number analysis was consistent with diploidy in all chromosomes. This is the first study of glomus tumors cytogenetics, to our knowledge, and the first to report biallelic inactivation of NF1 secondary to mitotic recombination of chromosome arm 17q in multiple NF1-associated glomus tumors. We have observed mitotic recombination in 22% of molecularly characterized NF1-associated glomus tumors, suggesting that it is a not uncommon mechanism in the reduction to homozygosity of the NF1 germline mutation in these tumors. In tumor NF1-G12, we hypothesize that mitotic recombination also unmasked (reduced to homozygosity) a hypomorphic germline allele in a gene on chromosome arm 17q associated with chromosomal instability, resulting in the extreme polyploidy. (C) 2012 Wiley Periodicals, Inc.
C1 [Stewart, Douglas R.; Pemov, Alexander] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Van Loo, Peter] Wellcome Trust Sanger Inst, Cambridge, England.
[Van Loo, Peter] VIB, Dept Mol & Dev Genet, Louvain, Belgium.
[Beert, Eline; Brems, Hilde; Legius, Eric] Catholic Univ Louvain, Dept Human Genet, B-3000 Louvain, Belgium.
[Sciot, Raf] Catholic Univ Louvain, Dept Pathol, B-3000 Louvain, Belgium.
[Pak, Evgenia] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Pak, Evgenia; Dutra, Amalia] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Stewart, DR (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7022B, Rockville, MD 20852 USA.
EM drstewart@mail.nih.gov
RI Van Loo, Peter/A-3287-2012; Lee, Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Van Loo, Peter/0000-0003-0292-1949
FU Division of Intramural Research of the National Human Genome Research
Institute (NHGRI); Division of Cancer Epidemiology and Genetics (DCEG)
of the National Cancer Institute; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; Fonds voor Wetenschappelijk
Onderzoek (FWO)-Vlaanderen [G.0578.06]; Cancer Foundation Stichting
tegen Kanker [C.0011-204-208]; KULeuven [GOA/11/010]; Vlaamse Liga tegen
Kanker
FX Supported by: The Division of Intramural Research of the National Human
Genome Research Institute (NHGRI), The Division of Cancer Epidemiology
and Genetics (DCEG) of the National Cancer Institute's Intramural
Research Program, The National Cancer Institute, National Institutes of
Health; Grant number: HHSN261200800001E; Fonds voor Wetenschappelijk
Onderzoek (FWO)-Vlaanderen; Grant number: G.0578.06; The Cancer
Foundation Stichting tegen Kanker; Grant number: C.0011-204-208;
KULeuven; Grant number: GOA/11/010; "Vlaamse Liga tegen Kanker".
NR 33
TC 10
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD MAY
PY 2012
VL 51
IS 5
BP 429
EP 437
DI 10.1002/gcc.21928
PG 9
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 903LN
UT WOS:000301118100002
PM 22250039
ER
PT J
AU Hirsch, D
Camps, J
Varma, S
Kemmerling, R
Stapleton, M
Ried, T
Gaiser, T
AF Hirsch, Daniela
Camps, Jordi
Varma, Sudhir
Kemmerling, Ralf
Stapleton, Mark
Ried, Thomas
Gaiser, Timo
TI A new whole genome amplification method for studying clonal evolution
patterns in malignant colorectal polyps
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID CHROMOSOMAL GAINS; CYTOGENETIC ANALYSIS; ARRAY CGH; HYBRIDIZATION;
PROGRESSION; CANCER; TUMORS; DNA; CARCINOMA; ADENOMA
AB To identify the genetic drivers of colorectal tumorigenesis, we applied array comparative genomic hybridization (aCGH) to 13 formalin-fixed paraffin-embedded (FFPE) samples of early, localized human colon adenocarcinomas arising in high-grade adenomas (so-called malignant polyps). These lesions are small and hence the amount of DNA is limited. Additionally, the quality of DNA is compromised due to the fragmentation as a consequence of formalin fixation. To overcome these problems, we optimized a newly developed isothermal whole genome amplification system (NuGEN Ovation (R) WGA FFPE System). Starting with 100 ng of FFPE DNA, the amplification system produced 4.01 +/- 0.29 mu g (mean +/- standard deviation) of DNA. The excellent quality of amplified DNA was further indicated by a high signal-to-noise ratio and a low derivative log2 ratio spread. Both, the amount of amplified DNA and aCGH performance were independent of the age of the FFPE blocks and the associated degradation of the extracted DNA. We observed losses of chromosome arms 5q and 18q in the adenoma components of the malignant polyp samples, while the embedded early carcinomas revealed losses of 8p, 17p, and 18, and gains of 7, 13, and 20. Aberrations detected in the adenoma components were invariably maintained in the embedded carcinomas. This approach demonstrates that using isothermally whole genome amplified FFPE DNA is technically suitable for aCGH. In addition to demonstrating the clonal origin of the adenoma and carcinoma part within a malignant polyp, the gain of chromosome arm 20q was an indicator for progression from adenoma to carcinoma. Published 2012 Wiley Periodicals, Inc.
C1 [Hirsch, Daniela; Camps, Jordi; Ried, Thomas; Gaiser, Timo] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Varma, Sudhir] HiThru Analyt, Bethesda, MD USA.
[Kemmerling, Ralf] Paracelsus Med Univ, Inst Pathol, Salzburg, Austria.
[Stapleton, Mark] NuGEN Technol Inc, San Carlos, CA USA.
RP Ried, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov; timo_gaiser@web.de
RI perumal, murugiah/D-1565-2012; Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
FU National Institutes of Health, National Cancer Institute; German
Academic Exchange Service; NuGEN
FX Supported by: The Intramural Research Program of the National Institutes
of Health, National Cancer Institute; RISE Program of the German
Academic Exchange Service.; DH received travel sponsoring from NuGEN to
the AACR Annual Meeting 2011. MS is employed by NuGEN, the manufacturer
of the Ovation (R) VR WGA FFPE System.
NR 30
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD MAY
PY 2012
VL 51
IS 5
BP 490
EP 500
DI 10.1002/gcc.21937
PG 11
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 903LN
UT WOS:000301118100009
PM 22334367
ER
PT J
AU Taverna, S
Flugy, A
Saieva, L
Kohn, EC
Santoro, A
Meraviglia, S
De Leo, G
Alessandro, R
AF Taverna, Simona
Flugy, Anna
Saieva, Laura
Kohn, Elise C.
Santoro, Alessandra
Meraviglia, Serena
De Leo, Giacomo
Alessandro, Riccardo
TI Role of exosomes released by chronic myelogenous leukemia cells in
angiogenesis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE exosomes; chronic myelogenous leukemia cells; endothelial cells; tumor
microenvironment
ID CHRONIC MYELOID-LEUKEMIA; VASCULAR ENDOTHELIAL-CELLS; TUMOR-GROWTH; K562
CELLS; CANCER; MICROVESICLES; MECHANISMS; JUNCTIONS; INHIBITION;
EXPRESSION
AB Our study is designed to assess if exosomes released from chronic myelogenous leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and beta-catenin from the endothelial cell surface. Functional characterization of exosomes isolated from CML patients confirmed the data obtained with exosomes derived from CML cell line. CML exosomes caused reorganization into tubes of HUVEC cells cultured on Matrigel. When added to Matrigel plugs in vivo, exosomes induced ingrowth of murine endothelial cells and vascularization of the Matrigel plugs. Our results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization.
C1 [Taverna, Simona; Flugy, Anna; Saieva, Laura; Meraviglia, Serena; De Leo, Giacomo; Alessandro, Riccardo] Univ Palermo, Dipartimento Biopatol & Biotecnol Med & Forensi, Sez Biol & Genet, I-90133 Palermo, Italy.
[Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Santoro, Alessandra] Osped Riuniti Villa Sofia Cervello, Lab Diagnost Integrata Oncoematol, Palermo, Italy.
RP Alessandro, R (reprint author), Univ Palermo, Dipartimento Biopatol & Biotecnol Med & Forensi, Sez Biol & Genet, Via Divisi 83, I-90133 Palermo, Italy.
EM ricale@unipa.it
FU Italian Association for Cancer Research (AIRC); University of Palermo;
MURST; Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Grant sponsors: Italian Association for Cancer Research (AIRC),
University of Palermo (International Cooperation), ex 60% MURST,
Intramural Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health
NR 47
TC 46
Z9 50
U1 3
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2012
VL 130
IS 9
BP 2033
EP 2043
DI 10.1002/ijc.26217
PG 11
WC Oncology
SC Oncology
GA 897XB
UT WOS:000300693100007
PM 21630268
ER
PT J
AU Liang, XS
Pfeiffer, RM
Wheeler, W
Maeder, D
Burdette, L
Yeager, M
Chanock, S
Tucker, MA
Goldstein, AM
Yang, XHR
AF Liang, Xueying Sharon
Pfeiffer, Ruth M.
Wheeler, William
Maeder, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
TI Genetic variants in DNA repair genes and the risk of cutaneous malignant
melanoma in melanoma-prone families with/without CDKN2A mutations
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE melanoma; cancer; genetics; DNA repair; association; pathway; CMM;
family
ID ASSOCIATION; CANCER; DAMAGE
AB Cutaneous malignant melanoma (CMM) is an etiologically heterogeneous disease with genetic, environmental (sun exposure) and host (pigmentation/nevi) factors and their interactions contributing to risk. Genetic variants in DNA repair genes may be particularly important since their altered function in response to sun exposure-related DNA damage maybe related to risk for CMM. However, systematic evaluations of genetic variants in DNA repair genes are limited, particularly in high-risk families. We comprehensively analyzed DNA repair gene polymorphisms and CMM risk in melanoma-prone families with/without CDKN2A mutations. A total of 586 individuals (183 CMM) from 53 families (23 CDKN2A (+), 30 CDKN2A (-)) were genotyped for 2964 tagSNPs in 131 DNA repair genes. Conditional logistic regression, conditioning on families, was used to estimate trend p-values, odds ratios and 95% confidence intervals for the association between CMM and each SNP separately, adjusted for age and sex. p-Values for SNPs in the same gene were combined to yield gene specific p-values. Two genes, POLN and PRKDC, were significantly associated with melanoma after Bonferroni correction for multiple testing (p = 0.0003 and 0.00035, respectively). DCLRE1B showed suggestive association (p = 0.0006). 28 similar to 56% of genotyped SNPs in these genes had single SNP p < 0.05. The most significant SNPs in POLN and PRKDC had similar effects in CDKN2A (+) and CDKN2A (-) families. Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations.
C1 [Liang, Xueying Sharon; Pfeiffer, Ruth M.; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Maeder, Dennis; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM royang@mail.nih.gov
RI Tucker, Margaret/B-4297-2015
FU NIH, NCI, DCEG
FX We are indebted to the participating families, whose generosity and
cooperation have made our study possible. We also acknowledge the
contributions to this work that were made by Virginia Pichler, Deborah
Zametkin, and Mary Fraser. This research was supported by the Intramural
Research Program of the NIH, NCI, DCEG.
NR 16
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2012
VL 130
IS 9
BP 2062
EP 2066
DI 10.1002/ijc.26231
PG 5
WC Oncology
SC Oncology
GA 897XB
UT WOS:000300693100010
PM 21671477
ER
PT J
AU Gage, JC
Ajenifuja, KO
Wentzensen, NA
Adepiti, AC
Eklund, C
Reilly, M
Hutchinson, M
Wacholder, S
Harford, J
Soliman, AS
Burk, RD
Schiffman, M
AF Gage, Julia C.
Ajenifuja, Kayode O.
Wentzensen, Nicolas A.
Adepiti, Akinfolarin C.
Eklund, Claire
Reilly, Mary
Hutchinson, Martha
Wacholder, Sholom
Harford, Joe
Soliman, Amr S.
Burk, Robert D.
Schiffman, Mark
TI The age-specific prevalence of human papillomavirus and risk of
cytologic abnormalities in rural Nigeria: Implications for
screen-and-treat strategies
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HPV prevalence; age; screening
ID CERVICAL INTRAEPITHELIAL NEOPLASIA; INTERNATIONAL INCIDENCE RATES;
GENOTYPE DISTRIBUTION; INFECTION; CANCER; WOMEN; CRYOTHERAPY; WORLDWIDE;
LESIONS; COHORT
AB Cervical screening for carcinogenic human papillomavirus (HPV) infection is being considered for low-income countries. Effectiveness requires targeted screening in older women in whom prevalent infections are more likely to be persistent and predictive of precancer. Some studies in West Africa have found unusually high HPV prevalences across all adult ages, which may reduce the positive predictive value (PPV) of HPV-based screening, if positivity in older women does not sufficiently predict elevated risk. We conducted a population-based study in rural Nigeria to identify HPV prevalence and associated cervical abnormalities. Using stratified random sampling, we enrolled women age 15+. Nonvirgins had a cervical exam including liquid-based cytology and PCR HPV DNA testing from residual cytology specimens. Two-thirds of invited women participated, and 14.7% had detectable carcinogenic HPV, a proportion that did not decline with age (p-trend = 0.36) and showed slight peaks in the 1529 and 6069 age groups. Among women of the age typically considered for screen-and-treat programs (3049 years), 12.8% were HPV positive, and the PPV for high-grade or worse cytology was 16.4%. Comparatively, women age < 30 were more likely to be HPV positive (18.9%, p = 0.03) with a lower PPV (4.2% p = 0.05). Among women age 50+ (typically excluded from screening in resource-poor settings because inexpensive treatment is not available), HPV positivity was 14.2% with a PPV of 13.9%. In Irun and similar settings where HPV does not decline with age, HPV-based screen-and-treat programs might be feasible for mid-adult women because prevalence is sufficiently low and positivity predicts elevated risk of more easily treated precancer.
C1 [Gage, Julia C.] NCI, Clin Genet Branch, DCEG, NIH,DHHS, Rockville, MD 20852 USA.
[Ajenifuja, Kayode O.; Adepiti, Akinfolarin C.] Obafemi Awolowo Univ, Dept Obstet Gynaecol & Perinatol, Ife, Nigeria.
[Eklund, Claire; Reilly, Mary; Hutchinson, Martha] Brown Univ, Women & Infants Hosp, Dept Pathol & Lab Med, Providence, RI USA.
[Harford, Joe] NCI, Off Int Affairs, NIH, DHHS, Rockville, MD 20852 USA.
[Soliman, Amr S.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pediat, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Gage, JC (reprint author), NCI, Clin Genet Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,MSC 7231, Rockville, MD 20852 USA.
EM gagej@mail.nih.gov
RI perumal, murugiah/D-1565-2012
FU National Cancer Institute [CA78527]; Einstein-Montefiore Center for AIDS
from the National Institutes of Health [AI-51519]; Einstein Cancer
Research Center from the National Cancer Institute [P30CA013330];
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services; NIH [HHSN261200900303P]
FX Grant sponsor: National Cancer Institute; Grant number: CA78527; Grant
sponsor: Einstein-Montefiore Center for AIDS from the National
Institutes of Health; Grant number: AI-51519; Grant sponsor: Einstein
Cancer Research Center from the National Cancer Institute; Grant number:
P30CA013330; This work was supported by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services and NIH contract
#HHSN261200900303P. The careHPV equipment and supplies used in our study
were donated by Qiagen Corporation (Gaithersburg, MD); careHPV is not
the subject of our report.
NR 29
TC 20
Z9 20
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2012
VL 130
IS 9
BP 2111
EP 2117
DI 10.1002/ijc.26211
PG 7
WC Oncology
SC Oncology
GA 897XB
UT WOS:000300693100016
PM 21630264
ER
PT J
AU Kolb, EA
Gorlick, R
Maris, JM
Keir, ST
Morton, CL
Wu, JR
Wozniak, AW
Smith, MA
Houghton, PJ
AF Kolb, E. Anders
Gorlick, Richard
Maris, John M.
Keir, Stephen T.
Morton, Christopher L.
Wu, Jianrong
Wozniak, Amy W.
Smith, Malcolm A.
Houghton, Peter J.
TI Combination testing (Stage 2) of the Anti-IGF-1 receptor antibody
IMC-A12 with rapamycin by the pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; IMC-A12; preclinical testing; rapamycin
ID GROWTH-FACTOR-II; RENAL-CELL CARCINOMA; HUMAN NEUROBLASTOMA; AUTOCRINE
GROWTH; TUMOR XENOGRAFTS; CANCER MODELS; IN-VIVO; RHABDOMYOSARCOMA;
CHEMOTHERAPY; TEMSIROLIMUS
AB Background IMC-A12, a fully human antibody that blocks ligand binding to the Type 1 insulin-like growth factor receptor, and rapamycin, a selective inhibitor of mTORC1 signaling, have both demonstrated significant antitumor activity against PPTP solid tumor models. Here we have evaluated antitumor activity of each agent individually and in combination against nine tumor models. Procedures. IMC-A12 was administered twice weekly and rapamycin was administered daily for 5 days per week for a planned 4 weeks. The impact of combining IMC-A12 with rapamycin was evaluated using two measures: (1) the "therapeutic enhancement'' measure, and (2) a linear regression model for time-to-event to formally evaluate for sub-and supra-additivity for the combination compared to the agents used alone. Results. Two osteosarcomas, and one Ewing sarcoma of the nine xenografts tested showed therapeutic enhancement. The combination effect was most dramatic for EW-5 for which PD2 responses of short duration were observed for both single agents and a prolonged PR response was observed for the combination. Both OS-2 and OS-9 showed significantly longer times to progression with the combination compared to either of the single agents, although objective response criteria were not met. Conclusions. The combination of IMC-A12 with rapamycin was well tolerated, and induced tumor responses that were superior to either single agent alone in several models. These studies confirm reports using other antibodies that inhibit IGF-1 receptor-mediated signaling that indicate enhanced therapeutic effect for this combination, and extend the range of histotypes to encompass additional tumors expressing IGF-1R where this approach may be effective. Pediatr Blood Cancer 2012;58:729-735. (C) 2011 Wiley Periodicals, Inc.
C1 [Kolb, E. Anders] Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, Wilmington, DE 19803 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Morton, Christopher L.; Wu, Jianrong; Wozniak, Amy W.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
RP Kolb, EA (reprint author), Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM eakolb@nemours.org
RI Houghton, Peter/E-3265-2011
FU National Cancer Institute [NO1-CM-42216, NO1-CM91001-03, CA21765,
CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
NO1-CM91001-03, CA21765, CA108786.
NR 31
TC 25
Z9 26
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2012
VL 58
IS 5
BP 729
EP 735
DI 10.1002/pbc.23157
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 901RM
UT WOS:000300984500012
PM 21630428
ER
PT J
AU Kolb, EA
Gorlick, R
Keir, ST
Maris, JM
Lock, R
Carol, H
Kurmasheva, RT
Reynolds, CP
Kang, MH
Wu, JR
Houghton, PJ
Smith, MA
AF Kolb, E. Anders
Gorlick, Richard
Keir, Stephen T.
Maris, John M.
Lock, Richard
Carol, Hernan
Kurmasheva, Raushan T.
Reynolds, C. Patrick
Kang, Min H.
Wu, Jianrong
Houghton, Peter J.
Smith, Malcolm A.
TI Initial testing (stage 1) by the pediatric preclinical testing program
of RO4929097, a ?-secretase inhibitor targeting notch signaling
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; Notch; preclinical testing
ID DIFFERENTIATION; LEUKEMIA; MODELS
AB RO4929097 is a potent and selective inhibitor of ?-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts. Pediatr Blood Cancer 2012; 58: 815818. (C) 2011 Wiley Periodicals, Inc.
C1 [Kolb, E. Anders] Alfred I DuPont Hosp Children, Dept Oncol, Wilmington, DE 19803 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[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.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kolb, EA (reprint author), Alfred I DuPont Hosp Children, Dept Oncol, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM eakolb@nemours.org
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013
OI Carol, Hernan/0000-0002-9443-8032;
FU National Cancer Institute [NO1-CM-42216, CA21765, CA16058, CA108786]
FX This work was supported by NO1-CM-42216, CA21765, CA16058, and CA108786
from the National Cancer Institute and used RO4929097 supplied by Roche
Pharmaceuticals, Inc. In addition to the authors this article represents
work contributed by the following: Sherry Ansher, Catherine A. Billups,
Joshua Courtright, Edward Favours, Henry S. Friedman, Danuta Gasinski,
Melissa Sammons, Chandra Tucker, Jianrong Wu, Joe Zeidner, Ellen Zhang,
and Jian Zhang. Children's Cancer Institute Australia for Medical
Research is affiliated with the University of New South Wales and Sydney
Children's Hospital.
NR 18
TC 12
Z9 13
U1 0
U2 3
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2012
VL 58
IS 5
BP 815
EP 818
DI 10.1002/pbc.23290
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 901RM
UT WOS:000300984500027
PM 22052798
ER
PT J
AU Lim, C
Sen, PK
Peddada, SD
AF Lim, Changwon
Sen, Pranab K.
Peddada, Shyamal D.
TI Accounting for uncertainty in heteroscedasticity in nonlinear regression
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Asymptotic normality; Dose-response study; Heteroscedasticity; Hill
model; M-estimation procedure; Preliminary test estimation; Toxicology
ID PARTIALLY LINEAR-MODELS; VARIANCE FUNCTION; LIKELIHOOD; ESTIMATORS;
SHRINKAGE; INFERENCE; ERRORS
AB Toxicologists and pharmacologists often describe toxicity of a chemical using parameters of a nonlinear regression model. Thus estimation of parameters of a nonlinear regression model is an important problem. The estimates of the parameters and their uncertainty estimates depend upon the underlying error variance structure in the model. Typically, a priori the researcher would not know if the error variances are homoscedastic (i.e., constant across dose) or if they are heteroscedastic (i.e., the variance is a function of dose). Motivated by this concern, in this paper we introduce an estimation procedure based on preliminary test which selects an appropriate estimation procedure accounting for the underlying error variance structure. Since outliers and influential observations are common in toxicological data, the proposed methodology uses M-estimators. The asymptotic properties of the preliminary test estimator are investigated: in particular its asymptotic covariance matrix is derived. The performance of the proposed estimator is compared with several standard estimators using simulation studies. The proposed methodology is also illustrated using a data set obtained from the National Toxicology Program. Published by Elsevier B.V.
C1 [Lim, Changwon; Peddada, Shyamal D.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Sen, Pranab K.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA.
[Sen, Pranab K.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
RP Peddada, SD (reprint author), NIEHS, Biostat Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM peddada@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU NIH, National Institute of Environmental Health Sciences [Z01
ES101744-04]
FX This research was supported, in part, by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences [Z01
ES101744-04]. We thank Drs. Gregg Dinse and Paramita Saha as well as the
editors and the referees for many important comments which helped to
improve the presentation of the manuscript.
NR 27
TC 7
Z9 7
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD MAY
PY 2012
VL 142
IS 5
BP 1047
EP 1062
DI 10.1016/j.jspi.2011.11.003
PG 16
WC Statistics & Probability
SC Mathematics
GA 896DW
UT WOS:000300546600003
PM 22345900
ER
PT J
AU Klauzinska, M
Baljinnyam, B
Raafat, A
Rodriguez-Canales, J
Strizzi, L
Greer, YE
Rubin, JS
Callahan, R
AF Klauzinska, Malgorzata
Baljinnyam, Bolormaa
Raafat, Ahmed
Rodriguez-Canales, Jaime
Strizzi, Luigi
Greer, Yoshimi Endo
Rubin, Jeffrey S.
Callahan, Robert
TI Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary
epithelial cells
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID BETA-CATENIN; TRANSGENIC MICE; WNT PATHWAY; GENE-EXPRESSION;
FAMILY-MEMBERS; TUMOR VIRUS; ACTIVATION; GLAND; LRP6; CARCINOGENESIS
AB Rspo2 was identified as a novel common integration site (CIS) for the mouse mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells. Co-expression of both genes resulted in an intermediate growth phenotype on plastic and had minor effects on the growth-promoting properties of Wnt1 in soft agar. However, individual Rspo2 and Wnt1 HC11 transfectants as well as the double transfectant were tumorigenic in athymic nude mice, with tumors from each line having distinctive histological characteristics. Rspo2 and Rspo2/Wnt1 tumors contained many spindle cells, consistent with an epithelialmesenchymal transformation (EMT) phenotype. When Rspo2 and Rspo2/Wnt1 tumor cells were transferred into naive mice, they exhibited greater metastatic activity than cells derived from Wnt1 tumors. For comparison, C57MG/Wnt1/Rspo2 co-transfectants exhibited invasive properties in three-dimensional (3D) Matrigel cultures that were not seen with cells transfected only with Wnt1 or Rspo2. Use of Dickkopf-1, a specific antagonist of the Wnt/beta-catenin pathway, or short hairpin RNA targeting beta-catenin expression demonstrated that the invasive activity was not mediated by beta-catenin. Our results indicate that Rspo2 and Wnt1 have mutually distinct effects on mammary epithelial cell growth and these effects are context-dependent. While Rspo2 and Wnt1 act synergistically in the beta-catenin pathway, other mechanisms are responsible for the invasive properties of stable double transfectants observed in 3D Matrigel cultures. J. Cell. Physiol. 227: 1960-1971, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Callahan, Robert] NCI, Oncogenet Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
[Baljinnyam, Bolormaa; Greer, Yoshimi Endo; Rubin, Jeffrey S.] NCI, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
[Rodriguez-Canales, Jaime] NCI, Laser Microdissect Core, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Strizzi, Luigi] Northwestern Univ, Childrens Mem Res Ctr, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Callahan, R (reprint author), NCI, Oncogenet Sect, Mammary Biol & Tumorigenesis Lab, NIH, 37 Convent Dr,Bldg 37,Rm 1118A, Bethesda, MD 20892 USA.
EM rc54d@nih.gov
OI Rodriguez-Canales, Jaime/0000-0002-0885-2377
FU NIH; National Cancer Institute; Center for Cancer Research
FX Contract grant sponsor: NIH.; Contract grant sponsor: National Cancer
Institute.; Contract grant sponsor: Center for Cancer Research.
NR 38
TC 13
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD MAY
PY 2012
VL 227
IS 5
BP 1960
EP 1971
DI 10.1002/jcp.22924
PG 12
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 879ZS
UT WOS:000299373900020
PM 21732367
ER
PT J
AU Robinette, SL
Holmes, E
Nicholson, JK
Dumas, ME
AF Robinette, Steven L.
Holmes, Elaine
Nicholson, Jeremy K.
Dumas, Marc E.
TI Genetic determinants of metabolism in health and disease: from
biochemical genetics to genome-wide associations
SO GENOME MEDICINE
LA English
DT Review
DE Metabonomics/metabolomics; Quantitative Trait Locus Mapping; Biochemical
Genetics; NMR; MS
ID QUANTITATIVE TRAIT LOCUS; MAGNETIC-RESONANCE-SPECTROSCOPY; TANDEM
MASS-SPECTROMETRY; SERUM LEPTIN LEVELS; SYSTEMS BIOLOGY; INBORN-ERRORS;
NMR-SPECTROSCOPY; H-1-NMR SPECTROSCOPY; SUSCEPTIBILITY LOCUS; PROFILING
PROCEDURES
AB Increasingly sophisticated measurement technologies have allowed the fields of metabolomics and genomics to identify, in parallel, risk factors of disease; predict drug metabolism; and study metabolic and genetic diversity in large human populations. Yet the complementarity of these fields and the utility of studying genes and metabolites together is belied by the frequent separate, parallel applications of genomic and metabolomic analysis. Early attempts at identifying co-variation and interaction between genetic variants and downstream metabolic changes, including metabolic profiling of human Mendelian diseases and quantitative trait locus mapping of individual metabolite concentrations, have recently been extended by new experimental designs that search for a large number of gene-metabolite associations. These approaches, including metabolomic quantitiative trait locus mapping and metabolomic genome-wide association studies, involve the concurrent collection of both genomic and metabolomic data and a subsequent search for statistical associations between genetic polymorphisms and metabolite concentrations across a broad range of genes and metabolites. These new data-fusion techniques will have important consequences in functional genomics, microbial metagenomics and disease modeling, the early results and implications of which are reviewed.
C1 [Robinette, Steven L.; Holmes, Elaine; Nicholson, Jeremy K.; Dumas, Marc E.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, London SW7 2AZ, England.
[Robinette, Steven L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Nicholson, JK (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, Sir Alexander Fleming Bldg,Exhibit Rd, London SW7 2AZ, England.
EM j.nicholson@imperial.ac.uk; m.dumas@imperial.ac.uk
RI Dumas, Marc/C-1736-2008; Nicholson, Jeremy/B-3395-2012
OI Dumas, Marc/0000-0001-9523-7024; Nicholson, Jeremy/0000-0002-8123-8349
FU NSF; Marshall Aid Commemoration Commission; Nestle [RDLS015375]; Agence
Nationale de la Recherche [ANR-08-GENO-030-02]; EU-FP7 EURATRANS
[HEALTH-F4-2010-241504]
FX SLR acknowledges support from the NSF Graduate Research Fellowship
Program and from the Marshall Aid Commemoration Commission. M-ED is
funded by Nestle (RDLS015375), Agence Nationale de la Recherche
(ANR-08-GENO-030-02), and EU-FP7 EURATRANS (HEALTH-F4-2010-241504).
NR 104
TC 16
Z9 16
U1 2
U2 31
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD APR 30
PY 2012
VL 4
AR 30
DI 10.1186/gm329
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 084WA
UT WOS:000314569200001
PM 22546284
ER
PT J
AU Xu, X
Veenstra, TD
AF Xu, Xia
Veenstra, Timothy D.
TI Concentration of endogenous estrogens and estrogen metabolites in the
NCI-60 human tumor cell lines
SO GENOME MEDICINE
LA English
DT Article
ID HUMAN-MELANOMA CELLS; PROGESTERONE-RECEPTORS; REPLACEMENT THERAPY;
CUTANEOUS MELANOMA; LUNG-CARCINOMA; BINDING-SITES; CANCER; AROMATASE;
ESTRADIOL; BREAST
AB Background: Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers.
Methods: In this study we systemically surveyed endogenous estrogen and estrogen metabolite levels in each of the NCI-60 human tumor cell lines, which include human breast, central nerve system, colon, ovarian, prostate, kidney and non-small cell lung cancers, as well as melanomas and leukemia. The absolute abundances of these metabolites were measured using a liquid chromatography-tandem mass spectrometry method that has been previously utilized for biological fluids such as serum and urine.
Results: Endogenous estrogens and estrogen metabolites were found in all NCI-60 human tumor cell lines and some were substantially elevated and exceeded the levels found in well known estrogen-dependent and estrogen receptor-positive tumor cells such as MCF-7 and T-47D. While estrogens were expected to be present at high levels in cell lines representing the female reproductive system (that is, breast and ovarian), other cell lines, such as leukemia and colon, also contained very high levels of these steroid hormones. The leukemia cell line RMPI-8226 contained the highest levels of estrone (182.06 pg/10(6) cells) and 17 beta-estradiol (753.45 pg/10(6) cells). In comparison, the ovarian cancer cell line with the highest levels of these estrogens contained only 19.79 and 139.32 pg/10(6) cells of estrone and 17 beta-estradiol, respectively. The highest levels of estrone and 17 beta-estradiol in breast cancer cell lines were only 8.45 and 87.37 pg/10(6) cells in BT-549 and T-47D cells, respectively.
Conclusions: The data provided evidence for the presence of significant amounts of endogenous estrogens and estrogen metabolites in cell lines not commonly associated with these steroid hormones. This broad discovery of endogenous estrogens and estrogen metabolites in these cell lines suggest that several human tumors may be beneficially treated using endocrine therapy aimed at estrogen biosynthesis and estrogen-related signaling pathways.
C1 [Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM veenstrat@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, 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 United States
Government.
NR 35
TC 7
Z9 7
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD APR 30
PY 2012
VL 4
AR 31
DI 10.1186/gm330
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 084WA
UT WOS:000314569200002
PM 22546321
ER
PT J
AU Soula, HA
Coulon, A
Beslon, G
AF Soula, Hedi A.
Coulon, Antoine
Beslon, Guillaume
TI Membrane microdomains emergence through non-homogeneous diffusion
SO BMC BIOPHYSICS
LA English
DT Article
DE Membrane domains; Non-homogeneous diffusion; Individual-based model
ID SINGLE-PARTICLE TRACKING; PLASMA-MEMBRANE; LIPID RAFTS; MONTE-CARLO;
CELL-MEMBRANES; CHOLESTEROL DEPLETION; ANOMALOUS DIFFUSION; LATERAL
DIFFUSION; MODEL MEMBRANES; PROTEIN DIFFUSION
AB Background: In the classical view, cell membrane proteins undergo isotropic random motion, that is a 2D Brownian diffusion that should result in an homogeneous distribution of concentration. It is, however, far from the reality: Membrane proteins can assemble into so-called microdomains (sometimes called lipid rafts) which also display a specific lipid composition. We propose a simple mechanism that is able to explain the colocalization of protein and lipid rafts.
Results: Using very simple mathematical models and particle simulations, we show that a variation of membrane viscosity directly leads to variation of the local concentration of diffusive particles. Since specific lipid phases in the membrane can account for diffusion variation, we show that, in such a situation, the freely diffusing proteins (or any other component) still undergo a Brownian motion but concentrate in areas of lower diffusion. The amount of this so-called overconcentration at equilibrium issimply related to the ratio of diffusion coefficients between zones of high and low diffusion. Expanding the model to include particle interaction, we show that inhomogeneous diffusion can impact particles clusterization as well. The clusters of particles were more numerous and appear for a lower value of interaction strength in the zones of low diffusion compared to zones of high diffusion.
Conclusion: Provided we assume stable viscosity heterogeneity in the membrane, our model propose a simple mechanism to explain particle concentration heterogeneity. It has also a non-trivial impact on density of particles when interaction is added. This could potentially have an impact on membrane chemical reactions and oligomerization.
C1 [Soula, Hedi A.] Univ Lyon, INSERM, UMR1060, F-69621 Villeurbanne, France.
[Beslon, Guillaume] Univ Lyon, CNRS INSA Lyon, LIRIS UMR5205, F-69621 Villeurbanne, France.
[Soula, Hedi A.; Beslon, Guillaume] INRIA, EPI BEAGLE, F-69603 Paris, France.
[Coulon, Antoine] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Soula, HA (reprint author), Univ Lyon, INSERM, UMR1060, F-69621 Villeurbanne, France.
EM hedi.soula@insa-lyon.fr
RI Beslon, Guillaume/D-7369-2014; Coulon, Antoine/A-9006-2012
FU Institut of Complex System of Rhones-Alphes (IXXI)
FX This work has been partly supported by the Institut of Complex System of
Rhones-Alphes (IXXI).
NR 60
TC 6
Z9 6
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2046-1682
J9 BMC BIOPHYS
JI BMC Biophys.
PD APR 30
PY 2012
VL 5
AR 6
DI 10.1186/2046-1682-5-6
PG 12
WC Biophysics
SC Biophysics
GA 059NR
UT WOS:000312712700001
PM 22546236
ER
PT J
AU Grewal, J
Wernicke, M
Zhang, J
AF Grewal, Jagteshwar
Wernicke, Meghan
Zhang, Jun
TI Early childhood development when second-trimester ultrasound dating
disagrees with last menstrual period: a prospective cohort study
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Gestational age discrepancy; Childhood development; Cognitive
functioning; LMP
ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH-RETARDATION; BIPARIETAL
DIAMETER; INCREASED RISK; PRETERM BIRTH; INFANTS; CHILDREN; PREGNANCY;
TERM; DISCREPANCY
AB Background: When an ultrasound-based estimate of gestational age (GA) is less (greater) than an estimate based on a definite last menstrual period, the fetus may grow slower (faster) than average. While the association between these discrepancies in GA estimates and adverse perinatal outcomes has been examined extensively, there is scant evidence about long-term effects, such as child neurodevelopment.
Methods: Using data from a prospective cohort study titled, NICHD Study of Successive Small-for-Gestational Age Births, we examined if GA discrepancies in early second trimester of pregnancy (17 weeks' gestation) are associated with: (1) impaired motor and mental function at 13 months (measured using Bayley Scales of Infant Development (Bayley)), and (2) impaired cognitive development at five years (assessed by Wechsler Preschool and Primary Scale of Intelligence - Revised Intelligence Quotient (WPPSI-R)) in the infant. The study population consisted of 572 (30% of the overall sample of 1,945) women who presented for prenatal care in Norway and Sweden between 1986 and 1988.
Results: Our results showed that GA discrepancies in early second trimester are significantly associated with birthweight. We found no significant relationship, however, with the Bayley development scores at 13 months and with the WPPSI-R IQ measures at five years.
Conclusions: GA discrepancies at 17 weeks' gestation are not associated child neurodevelopment. These discrepancies do, however, relate to birthweights, providing a basis for detecting fetal growth patterns early in the second trimester of pregnancy. Our study, however, was unable to evaluate the impact of first-trimester discrepancies on impaired neurodevelopment in the infant.
C1 [Grewal, Jagteshwar; Wernicke, Meghan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE & Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China.
RP Grewal, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Executive Blvd,Room 7B03G, Rockville, MD 20852 USA.
EM grewalja@mail.nih.gov
OI Grewal, Jagteshwar/0000-0002-0141-4876
FU Intramural Research Program of the 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 30
TC 0
Z9 0
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD APR 30
PY 2012
VL 12
AR 32
DI 10.1186/1471-2393-12-32
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 038ZG
UT WOS:000311212000001
PM 22545943
ER
PT J
AU Sraj, I
Szatmary, AC
Desai, SA
Marr, DWM
Eggleton, CD
AF Sraj, Ihab
Szatmary, Alex C.
Desai, Sanjay A.
Marr, David W. M.
Eggleton, Charles D.
TI Erythrocyte deformation in high-throughput optical stretchers
SO PHYSICAL REVIEW E
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; BLOOD-CELLS; RHEOLOGIC PROPERTIES; LASER TRAP;
SHEAR-FLOW; DEFORMABILITY; AGGREGATION; SIMULATION; MEMBRANES; TWEEZERS
AB Optical stretchers can be used to quantify elastic and homeostatic properties of cells. Because they can apply forces to cells without requiring direct contact, they may noninvasively measure mechanical properties related to cell and membrane health. Present-day optical stretchers are, however, limited to measurements on individual stationary cells, limiting throughput. To overcome this limitation and allow study of variations in cell populations, we recently developed and tested a microfluidic chamber that measures optical stretching parameters for erythrocytes under dynamic flowing conditions. The method uses a single linear diode laser bar and permitted measurements at low flow rates and higher throughput. Here, we numerically investigate the feasibility of further increasing the measurement rates of the optical stretcher in parameter domains where hydrodynamic and optical forces are of comparable magnitude. To do this we couple a recently implemented dynamic optical ray-tracing technique with a fluid-structure interaction solver to simulate the deformation of osmotically swollen erythrocytes in fluid flow of variable rate. Our results demonstrate that a detectable steady-state stretch is induced at nominal optical powers and flow rates. In addition, we find that flow rates can be increased significantly with no major effect on net cell stretch showing the feasibility of application of this technique at greatly increased throughputs.
C1 [Sraj, Ihab; Szatmary, Alex C.; Eggleton, Charles D.] Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA.
[Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Marr, David W. M.] Colorado Sch Mines, Dept Chem & Biol Engn, Golden, CO 80401 USA.
RP Eggleton, CD (reprint author), Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA.
EM eggleton@umbc.edu
RI Szatmary, Alex/K-1971-2012;
OI Szatmary, Alex/0000-0002-2986-5281; Sraj, Ihab/0000-0002-6158-472X
FU National Institutes of Health [R01 AI079347-01]
FX This research was funded by the National Institutes of Health Grant No.
R01 AI079347-01. We thank the Pittsburgh Supercomputing Center for
computational resources under DAC allocation MCB090098.
NR 45
TC 10
Z9 10
U1 3
U2 23
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 2470-0045
EI 2470-0053
J9 PHYS REV E
JI Phys. Rev. E
PD APR 30
PY 2012
VL 85
IS 4
AR 041923
DI 10.1103/PhysRevE.85.041923
PN 1
PG 9
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 967IF
UT WOS:000305899700003
PM 22680514
ER
PT J
AU Kim, SH
Xiao, S
Shive, H
Collins, PL
Samal, SK
AF Kim, Shin-Hee
Xiao, Sa
Shive, Heather
Collins, Peter L.
Samal, Siba K.
TI Replication, Neurotropism, and Pathogenicity of Avian Paramyxovirus
Serotypes 1-9 in Chickens and Ducks
SO PLOS ONE
LA English
DT Article
ID NEWCASTLE-DISEASE VIRUS; COMPLETE GENOME SEQUENCE;
HEMAGGLUTININ-NEURAMINIDASE PROTEINS; FUSION PROTEIN; PROTECTIVE
IMMUNITY; CLEAVAGE SITE; YUCAIPA; TURKEYS; INFECTION; VIRULENCE
AB Avian paramyxovirus (APMV) serotypes 1-9 have been isolated from many different avian species. APMV-1 (Newcastle disease virus) is the only well-characterized serotype, because of the high morbidity, mortality, and economic loss caused by highly virulent strains. Very little is known about the pathogenesis, replication, virulence, and tropism of the other APMV serotypes. Here, this was evaluated for prototypes strains of APMV serotypes 2-9 in cell culture and in chickens and ducks. In cell culture, only APMV-1, -3 and -5 induced syncytium formation. In chicken DF1 cells, APMV-3 replicated with an efficiency approaching that of APMV-1, while APMV-2 and -5 replicated to lower, intermediate titers and the others were much lower. Mean death time (MDT) assay in chicken eggs and intracerebral pathogenicity index (ICPI) test in 1-day-old SPF chicks demonstrated that APMV types 2-9 were avirulent. Evaluation of replication in primary neuronal cells in vitro as well as in the brains of 1-day-old chicks showed that, among types 2-9, only APMV-3 was neurotropic, although this virus was not neurovirulent. Following intranasal infection of 1-day-old and 2-week-old chickens, replication of APMV types 2-9 was mostly restricted to the respiratory tract, although APMV-3 was neuroinvasive and neurotropic (but not neurovirulent) and also was found in the spleen. Experimental intranasal infection of 3-week-old mallard ducks with the APMVs did not produce any clinical signs (even for APMV-1) and exhibited restricted viral replication of the APMVs (including APMV-1) to the upper respiratory tract regardless of their isolation source, indicating avirulence of APMV types 1-9 in mallard ducks. The link between the presence of a furin cleavage site in the F protein, syncytium formation, systemic spread, and virulence that has been well-established with APMV-1 pathotypes was not evident with the other APMV serotypes.
C1 [Kim, Shin-Hee; Xiao, Sa; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Shive, Heather] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Kim, SH (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU National Institute of Allergy and Infection Diseases (NIAID)
[N01A060009]; NIAID, National Institutes of Health Intramural Research
Program
FX This research was supported by National Institute of Allergy and
Infection Diseases (NIAID) contract no N01A060009 (85% support) and
NIAID, National Institutes of Health Intramural Research Program (15%
support). The views expressed herein do not necessarily reflect the
official policies of the Department of Health and Human Services, nor
does mention of trade names, commercial practices, or organizations
imply endorsement by the United States Government. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 45
TC 17
Z9 17
U1 1
U2 7
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 APR 30
PY 2012
VL 7
IS 4
AR e34927
DI 10.1371/journal.pone.0034927
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UL
UT WOS:000305340200007
PM 22558104
ER
PT J
AU Lea, WA
Simeonov, A
AF Lea, Wendy A.
Simeonov, Anton
TI Differential Scanning Fluorometry Signatures as Indicators of Enzyme
Inhibitor Mode of Action: Case Study of Glutathione S-Transferase
SO PLOS ONE
LA English
DT Article
ID PROMOTE PROTEIN STABILITY; ELECTROPHILE BINDING-SITE; THERMAL SHIFT
ASSAYS; PI CLASS GLUTATHIONE; SCHISTOSOMA-JAPONICUM; ETHACRYNIC-ACID;
CONFORMATIONAL STABILITY; 3-DIMENSIONAL STRUCTURE; SCREENING METHODS;
DRUG DISCOVERY
AB Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization.
C1 [Lea, Wendy A.; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
RP Lea, WA (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU Molecular Libraries of Initiative of the NIH Roadmap for Medical
Research; Intramural Research Program of the NHGRI, NIH
FX Funding by the Molecular Libraries of Initiative of the NIH Roadmap for
Medical Research, and the Intramural Research Program of the NHGRI, NIH,
is hereby gratefully acknowledged. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
TC 11
Z9 11
U1 2
U2 11
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 APR 30
PY 2012
VL 7
IS 4
AR e36219
DI 10.1371/journal.pone.0036219
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UL
UT WOS:000305340200051
PM 22558390
ER
PT J
AU Piskulic, D
Addington, J
Cadenhead, KS
Cannon, TD
Cornblatt, BA
Heinssen, R
Perkins, DO
Seidman, LJ
Tsuang, MT
Walker, EF
Woods, SW
McGlashan, TH
AF Piskulic, Danijela
Addington, Jean
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
Heinssen, Robert
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
McGlashan, Thomas H.
TI Negative symptoms in individuals at clinical high risk of psychosis
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Psychosis prodrome; Negative symptoms; Conversion to psychosis;
Longitudinal study; NAPLS1 project
ID EPISODE PSYCHOSIS; MENTAL STATES; SCHIZOPHRENIA; SCALE; PREDICTION;
TRANSITION; PRODROME
AB Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n = 138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Piskulic, Danijela] Univ Calgary, Mental Hlth Ctr Res & Educ, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB T2N 4Z6, Canada.
[Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol & Psychiat & Biobehav Sci, Los Angeles, CA USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
[Heinssen, Robert] NIMH, Schizophrenia Spectrum Disorders Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Woods, Scott W.; McGlashan, Thomas H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
RP Piskulic, D (reprint author), Univ Calgary, Mental Hlth Ctr Res & Educ, Hotchkiss Brain Inst, Dept Psychiat, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada.
EM dpiskuli@ucalgary.ca
FU National Institute of Mental Health [U01 MH066160, U01 MH066134, R01
MH60720, K24 MH76191, R01 MH065079, R01 MH061523, R01 MH066069, K23
MH01905, R18 MH 43518, R01 MH065562, P50 MH080272, R21MH075027,
RO1MH062066, K05MH01654]; Donaghue Foundation; Eli Lilly Co.
FX This work was supported by the National Institute of Mental Health
(grant numbers U01 MH066160 to SWW, U01 MH066134 to JA, R01 MH60720 and
K24 MH76191 to KSC, R01 MH065079 to TDC, R01 MH061523 to BAC, R01
MH066069 and K23 MH01905to DOP, R18 MH 43518 (MTT and LJS), R01 MH065562
and P50 MH080272 to LJS, R21MH075027 to MTT, RO1MH062066 to EFW,
K05MH01654 to THM); Donaghue Foundation (to SWW); and Eli Lilly & Co.
(to THM, JA, and DOP).
NR 26
TC 54
Z9 56
U1 3
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD APR 30
PY 2012
VL 196
IS 2-3
BP 220
EP 224
DI 10.1016/j.psychres.2012.02.018
PG 5
WC Psychiatry
SC Psychiatry
GA 962MG
UT WOS:000305548600009
PM 22445704
ER
PT J
AU Bedford, T
Rambaut, A
Pascual, M
AF Bedford, Trevor
Rambaut, Andrew
Pascual, Mercedes
TI Canalization of the evolutionary trajectory of the human influenza virus
SO BMC BIOLOGY
LA English
DT Article
ID A VIRUS; SEASONAL INFLUENZA; POSITIVE SELECTION; DYNAMICS; TRANSMISSION;
MODEL; H3N2; ESCAPE; IMPACT; DRIFT
AB Background: Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. However, despite strong pressure to evolve away from human immunity and to diversify in antigenic phenotype, H3N2 influenza shows paradoxically limited genetic and antigenic diversity present at any one time. Here, we propose a simple model of antigenic evolution in the influenza virus that accounts for this apparent discrepancy.
Results: In this model, antigenic phenotype is represented by a N-dimensional vector, and virus mutations perturb phenotype within this continuous Euclidean space. We implement this model in a large-scale individual-based simulation, and in doing so, we find a remarkable correspondence between model behavior and observed influenza dynamics. This model displays rapid evolution but low standing diversity and simultaneously accounts for the epidemiological, genetic, antigenic, and geographical patterns displayed by the virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis.
Conclusions: Selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable. In the model, the influenza population shows a 1- to 2-year timescale of repeatability, suggesting a window in which evolutionary dynamics could be, in theory, predictable.
C1 [Bedford, Trevor; Pascual, Mercedes] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Bedford, Trevor; Pascual, Mercedes] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
[Bedford, Trevor; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bedford, T (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM t.bedford@ed.ac.uk
OI Bedford, Trevor/0000-0002-4039-5794; Rambaut, Andrew/0000-0003-4337-3707
FU European Molecular Biology Organization
FX TB holds a Long-Term Fellowship from the European Molecular Biology
Organization. AR works as a part of the Interdisciplinary Centre for
Human and Avian Influenza Research (ICHAIR) and the University of
Edinburgh's Centre for Immunity, Infection and Evolution (CIIE). MP is
an investigator of the Howard Hughes Medical Institute.
NR 42
TC 31
Z9 31
U1 1
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD APR 30
PY 2012
VL 10
AR 38
DI 10.1186/1741-7007-10-38
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 957QO
UT WOS:000305178000001
PM 22546494
ER
PT J
AU Di, XD
Andrews, DMK
Tucker, CJ
Yu, LD
Moore, AB
Zheng, XL
Castro, L
Hermon, T
Xiao, H
Dixon, D
AF Di, Xudong
Andrews, Danica M. K.
Tucker, Charles J.
Yu, Linda
Moore, Alicia B.
Zheng, Xiaolin
Castro, Lysandra
Hermon, Tonia
Xiao, Hang
Dixon, Darlene
TI A high concentration of genistein down-regulates activin A, Smad3 and
other TGF-beta pathway genes in human uterine leiomyoma cells
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE activin A; genistein; leiomyoma; myometrium; oligonucleotide array
sequence analysis; Smad3 protein; transforming growth factor beta
ID GROWTH-FACTOR-BETA; BREAST-CANCER CELLS; HORMONE ANALOG THERAPY;
IN-VITRO; EXPRESSION; PROLIFERATION; MICROARRAY; METASTASIS; INHIBITION;
FIBROIDS
AB Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis (TM), we identified genes (up- or down-regulated, >= 1.5 fold, P <= 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 mu g/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta 2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that downregulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.
C1 [Di, Xudong; Yu, Linda; Moore, Alicia B.; Zheng, Xiaolin; Castro, Lysandra; Hermon, Tonia; Dixon, Darlene] Natl Inst Environm Hlth Sci, Mol Pathogenesis Grp, Natl Toxicol Program NTP, Labs Branch,NTP,NIH,DHHS, Res Triangle Pk, NC 27709 USA.
[Andrews, Danica M. K.; Tucker, Charles J.] Natl Inst Environm Hlth Sci, Microarray Grp, Mol Toxicol Lab, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
[Di, Xudong] Bur Hlth, Changzhou 213159, Peoples R China.
[Xiao, Hang] Nanjing Med Univ, Sch Publ Hlth, Dept Toxicol, Nanjing 210029, Jiangsu, Peoples R China.
RP Dixon, D (reprint author), Natl Inst Environm Hlth Sci, Mol Pathogenesis Grp, Natl Toxicol Program NTP, Labs Branch,NTP,NIH,DHHS, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
FU National Toxicology Program (NTP); NIH; National Institute of
Environmental Health Sciences (NIEHS)
FX The authors would like to thank Ms. Maria Sifre for her expert
assistance with the flow cytometry studies and acknowledge the editorial
assistance of the National Institutes of Health (NIH) Fellows Editorial
Board. This research was supported by the National Toxicology Program
(NTP) and the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (NIEHS). This article may be the work
product of an employee or group of employees of the NIEHS, NTP, NIH,
however, the statements, opinions or conclusions contained therein do
not necessarily represent the statements, opinions or conclusions of
NIEHS, NTP, NIH or the United States government.
NR 34
TC 15
Z9 16
U1 1
U2 8
PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
PI SEOUL
PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1226-3613
J9 EXP MOL MED
JI Exp. Mol. Med.
PD APR 30
PY 2012
VL 44
IS 4
BP 281
EP 292
DI 10.3858/emm.2012.44.4.024
PG 12
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 936UZ
UT WOS:000303616800004
PM 22228119
ER
PT J
AU Petrie, RJ
Gavara, N
Chadwick, RS
Yamada, KM
AF Petrie, Ryan J.
Gavara, Nuria
Chadwick, Richard S.
Yamada, Kenneth M.
TI Nonpolarized signaling reveals two distinct modes of 3D cell migration
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID LIVING CELLS; AMEBOID MOVEMENT; DIFFERENTIAL REGULATION;
EXTRACELLULAR-MATRIX; NONLINEAR ELASTICITY; RAC ACTIVATION; STRESS
FIBERS; LEADING-EDGE; ACTIN; FIBROBLASTS
AB We search in this paper for context-specific modes of three-dimensional (3D) cell migration using imaging for phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and active Rac1 and Cdc42 in primary fibroblasts migrating within different 3D environments. In 3D collagen, PIP3 and active Rac1 and Cdc42 were targeted to the leading edge, consistent with lamellipodia-based migration. In contrast, elongated cells migrating inside dermal explants and the cell-derived matrix (CDM) formed blunt, cylindrical protrusions, termed lobopodia, and Rac1, Cdc42, and PIP3 signaling was nonpolarized. Reducing RhoA, Rho-associated protein kinase (ROCK), or myosin II activity switched the cells to lamellipodia-based 3D migration. These modes of 3D migration were regulated by matrix physical properties. Specifically, experimentally modifying the elasticity of the CDM or collagen gels established that nonlinear elasticity supported lamellipodia-based migration, whereas linear elasticity switched cells to lobopodia-based migration. Thus, the relative polarization of intracellular signaling identifies two distinct modes of 3D cell migration governed intrinsically by RhoA, ROCK, and myosin II and extrinsically by the elastic behavior of the 3D extracellular matrix.
C1 [Petrie, Ryan J.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Gavara, Nuria; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD 20892 USA.
RP Petrie, RJ (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM petrier@mail.nih.gov; kyamada@mail.nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU National Institute of Dental and Craniofacial Research; National
Institute on Deafness and Other Communication Disorders at the National
Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Institute of Dental and Craniofacial Research and the National
Institute on Deafness and Other Communication Disorders at the National
Institutes of Health.
NR 79
TC 137
Z9 137
U1 4
U2 47
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 APR 30
PY 2012
VL 197
IS 3
BP 439
EP 455
DI 10.1083/jcb.201201124
PG 17
WC Cell Biology
SC Cell Biology
GA 934SU
UT WOS:000303467800012
PM 22547408
ER
PT J
AU Yuan, A
Xu, JF
Yue, QQ
Zheng, G
AF Yuan, Ao
Xu, Jinfeng
Yue, Qingqi
Zheng, Gang
TI Detecting case-control expression quantitative trait loci using locally
most powerful or maximin robust rank tests
SO STATISTICS IN MEDICINE
LA English
DT Article
DE case-control study; eQTL; gene expression; genome wide; locally most
powerful rank test; maximin efficiency robust test; quantitative trait
loci
ID GENE-EXPRESSION; NONPARAMETRIC TEST; ASSOCIATION TESTS; EFFICIENCY;
STATISTICS; LINKAGE
AB In testing genome-wide gene expression quantitative trait loci, efficiency robust statistical methods and their computational convenience are most relevant. For this purpose, we propose to use a modified locally most powerful rank test for the analysis of case-control expression data. This modified rank test statistic is computationally simple, robust for non-normally distributed expression data, and asymptotically locally most powerful. It depends on the specification of a location distribution form for data but is not sensitive to misspecifications. When such a location distribution form cannot be specified, we apply Gastwirth's maximin efficiency robust rank test to gene expression data to maximize the worst Pitman asymptotic relative efficiency among a family of location distributions. We conduct simulation studies to assess their performance and use an application to real data for illustration. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Yuan, Ao; Yue, Qingqi] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA.
[Xu, Jinfeng] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore.
[Zheng, Gang] DCVS Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA.
RP Yuan, A (reprint author), Howard Univ, Natl Human Genome Ctr, 2216 6th St NW, Washington, DC 20059 USA.
EM yuanao@hotmail.com
OI Xu, Jinfeng/0000-0002-3165-2015
FU National University of Singapore [R-155-000-112-112]; National Center
for Research Resources (NIH) [2G12RR003048]
FX Xu's work is supported by a grant from the National University of
Singapore (R-155-000-112-112). Yuan's work is supported in part by the
National Center for Research Resources (NIH grant no. 2G12RR003048). We
thank two referees and the associate editor for their very helpful
comments and insight, which greatly improved our presentation.
NR 40
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD APR 30
PY 2012
VL 31
IS 9
BP 887
EP 900
DI 10.1002/sim.4461
PG 14
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 923JO
UT WOS:000302615800007
PM 22173706
ER
PT J
AU Obolensky, OI
Wu, WW
Shen, RF
Yu, YK
AF Obolensky, O. I.
Wu, Wells W.
Shen, Rong-Fong
Yu, Yi-Kuo
TI Using dissociation energies to predict observability of b- and y-peaks
in mass spectra of short peptides
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID COLLISION-INDUCED DISSOCIATION; DENSITY-FUNCTIONAL THEORY;
SURFACE-INDUCED DISSOCIATION; MAIN FRAGMENTATION PATHWAYS; AMIDE
BOND-CLEAVAGE; FT-ICR MS; PROTONATED TRIPEPTIDES; GLY-XXX; KINETIC
METHOD; GAS-PHASE
AB RATIONALE: Peptide identification reliability can be improved by excluding from analysis those m/z peaks of candidate peptides which cannot be observed in practice due to various physical, chemical or thermodynamic considerations. We propose using dissociation energies (as opposed to proton affinities) as a predictor of observability of different m/z peaks in spectra of short peptides.
METHODS: Mass spectra of the tetrapeptides AAAA, AAFA, AAVA, AFAA, AVAA, AFFA, and AVVA were measured in the collision-induced dissociation (CID) activation mode on a grid of activation times 0.05 to 100 ms and normalized collision energy 10 to 35%. The lowest energy geometries and vibrational spectra were calculated for the precursor ions and their charged and neutral fragments using density functional theory (DFT) at the TPSS/6-31G(d, p) level. Dissociation energies were calculated for all fragmentation channels leading to b- or y-fragments.
RESULTS: It is demonstrated that m/z peaks observed in the mass spectra correspond to the fragmentation channels with the lowest dissociation energies. Using 50 kcal/mol as the cut-off value of dissociation energy, it was predicted that 28 out of 42 possible peaks in the b- and y-series of the seven tetrapeptides can be observed in mass spectra. In the experiments, 26 b- or y-peaks were observed, all of which are among the 28 predicted ones.
CONCLUSIONS: The use of dissociation energies generalizes the use of proton affinities for semi-quantitative predictions of relative intensities of different m/z peaks of short peptides. Further advances in this direction will pave the way for reliable quantitative predictions and, hence, for a significant improvement in robustness and accuracy of peptide and protein identification tools. Published in 2012 by John Wiley & Sons, Ltd.
C1 [Obolensky, O. I.; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Wu, Wells W.] NIA, NIH, Baltimore, MD 21224 USA.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Obolensky, OI (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM obolensk@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov
RI Obolensky, Oleg/A-5839-2008
OI Obolensky, Oleg/0000-0003-3315-1828
FU NIH, NLM
FX We thank Dr. Julia Laskin and Dr. Aleksey Ogurtsov for useful
discussions. This research was supported by the Intramural Research
Program of the NIH, NLM. The computations were carried out on the
Biowulf computer cluster at the National Institutes of Health, Bethesda,
MD, USA (http://biowulf.nih.gov).
NR 58
TC 3
Z9 3
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-4198
EI 1097-0231
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD APR 30
PY 2012
VL 26
IS 8
BP 915
EP 920
DI 10.1002/rcm.6180
PG 6
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 904FP
UT WOS:000301179800005
PM 22396027
ER
PT J
AU Kawel, N
Nacif, M
Zavodni, A
Jones, J
Liu, ST
Sibley, CT
Bluemke, DA
AF Kawel, Nadine
Nacif, Marcelo
Zavodni, Anna
Jones, Jacquin
Liu, Songtao
Sibley, Christopher T.
Bluemke, David A.
TI T1 mapping of the myocardium: intra-individual assessment of
post-contrast T1 time evolution and extracellular volume fraction at 3T
for Gd-DTPA and Gd-BOPTA
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE T1 mapping; Modified Look-Locker Inversion Recovery; Extracellular
volume fraction; ECV; Gadobenate dimeglumine; Gadopentetate dimeglumine
ID CARDIOVASCULAR MAGNETIC-RESONANCE; DOSE GADOBENATE DIMEGLUMINE;
GADOPENTETATE DIMEGLUMINE; PARTITION-COEFFICIENT; HEART; T-1; FIBROSIS;
HUMANS; BLOOD; LIVER
AB Purpose: Myocardial T1 relaxation time (T1 time) and extracellular volume fraction (ECV) are altered in patients with diffuse myocardial fibrosis. The purpose of this study was to perform an intra-individual assessment of normal T1 time and ECV for two different contrast agents.
Methods: A modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired at 3 T in 24 healthy subjects (8 men; 28 +/- 6 years) at mid-ventricular short axis pre-contrast and every 5 min between 5-45 min after injection of a bolus of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist (R)) (exam 1) and 0.1 mmol/kg gadobenate dimeglumine (Gd-BOPTA; Multihance (R)) (exam 2) during two separate scanning sessions. T1 times were measured in myocardium and blood on generated T1 maps. ECVs were calculated as (Delta R1(myocardium)/Delta R1(blood)) * (1-hematocrit).
Results: Mean pre-contrast T1 relaxation times for myocardium and blood were similar for both the first and second CMR exam (p > 0.5). Overall mean post-contrast myocardial T1 time was 15 +/- 2 ms (2.5 +/- 0.7%) shorter for Gd-DTPA at 0.15 mmol/kg compared to Gd-BOPTA at 0.1 mmol/kg (p < 0.01) while there was no significant difference for T1 time of blood pool (p > 0.05). Between 5 and 45 minutes after contrast injection, mean ECV values increased linearly with time for both contrast agents from 0.27 +/- 0.03 to 0.30 +/- 0.03 (p < 0.0001). Mean ECV values were slightly higher (by 0.01, p < 0.05) for Gd-DTPA compared to Gd-BOPTA. Inter-individual variation of ECV was higher (CV 8.7% [exam 1, Gd-DTPA] and 9.4% [exam 2, Gd-BOPTA], respectively) compared to variation of pre-contrast myocardial T1 relaxation time (CV 4.5% [exam 1] and 3.0% [exam 2], respectively). ECV with Gd-DTPA was highly correlated to ECV by Gd-BOPTA (r = 0.803; p < 0.0001).
Conclusion: In comparison to pre-contrast myocardial T1 relaxation time, variation in ECV values of normal subjects is larger. However, absolute differences in ECV between Gd-DTPA and Gd-BOPTA were small and rank correlation was high. There is a small and linear increase in ECV over time, therefore ideally images should be acquired at the same delay after contrast injection.
C1 [Kawel, Nadine; Nacif, Marcelo; Zavodni, Anna; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, NIH, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI Sibley, Christopher/C-9900-2013;
OI Bluemke, David/0000-0002-8323-8086
FU NIH
FX This study was supported by the NIH intramural research program.
NR 35
TC 49
Z9 50
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD APR 28
PY 2012
VL 14
AR 26
DI 10.1186/1532-429X-14-26
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 979FJ
UT WOS:000306801100001
PM 22540153
ER
PT J
AU Gyombolai, P
Pap, D
Turu, G
Catt, KJ
Bagdy, G
Hunyady, L
AF Gyombolai, Pal
Pap, Dorottya
Turu, Gabor
Catt, Kevin J.
Bagdy, Gyoergy
Hunyady, Laszlo
TI Regulation of endocannabinoid release by G proteins: A paracrine
mechanism of G protein-coupled receptor action
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Endocannabinoid; CB1; GPCR; Angiotensin II
ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CANNABINOID CB1 RECEPTOR;
SYMPATHO-ADRENOMEDULLARY OUTFLOW; MIDDLE CEREBRAL-ARTERY; ENDOGENOUS
CANNABINOIDS; ANGIOTENSIN-II; METABOTROPIC GLUTAMATE; NEOCORTICAL
INTERNEURONS; DIACYLGLYCEROL LIPASE; SYNAPTIC-TRANSMISSION
AB In the past years, the relationship between the endocannabinoid system (ECS) and other hormonal and neuromodulatory systems has been intensively studied. G protein-coupled receptors (GPCRs) can stimulate endocannabinoid (eCB) production via activation of G(q/11) proteins and, in some cases, G(s) proteins. In this review, we summarize the pathways through which GPCR activation can trigger eCB release, as well as the best known examples of this process throughout the body tissues. Angiotensin II-induced activation of AT(1) receptors, similar to other G(q/11)-coupled receptors, can lead to the formation of 2-arachidonoylglycerol (2-AG), an important eCB. The importance of eCB formation in angiotensin II action is supported by the finding that the hypertensive effect of angiotensin II, injected directly into the hypothalamic paraventricular nucleus of anaesthetized rats, can be abolished by AM251, an inverse agonist of CB1 cannabinoid receptors (CB(1)Rs). We conclude that activation of the ECS should be considered as a general consequence of the stimulation of GG(q/11)-coupled receptors, and may mediate some of the physiological effects of GPCRs. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Gyombolai, Pal; Turu, Gabor; Hunyady, Laszlo] Semmelweis Univ, Dept Physiol, Fac Med, H-1444 Budapest, Hungary.
[Pap, Dorottya; Bagdy, Gyoergy] Semmelweis Univ, Fac Pharm, H-1444 Budapest, Hungary.
[Catt, Kevin J.] NICHHD, Sect Hormonal Regulat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Bagdy, Gyoergy] Semmelweis Univ, Grp Neuropsychopharmacol & Neurochem, H-1444 Budapest, Hungary.
[Hunyady, Laszlo] Semmelweis Univ, Lab Neurobiochem & Mol Physiol, H-1444 Budapest, Hungary.
[Bagdy, Gyoergy; Hunyady, Laszlo] Hungarian Acad Sci, Budapest, Hungary.
RP Hunyady, L (reprint author), Semmelweis Univ, Dept Physiol, Fac Med, POB 259, H-1444 Budapest, Hungary.
EM hunyady@eok.sote.hu
OI Turu, Gabor/0000-0002-4421-3812; Bagdy, Gyorgy/0000-0001-8141-3410
FU Hungarian Science Foundation [OTKA NK-072661]; Hungarian Ministry of
Public Health [ETT 337/2009, ETT 318/2009]; EU [LSHM-CT-2004-503474];
[TAMOP-4.2.1.B-09/1/KMR-2010-0001]
FX The help provided by Jolan Jozan in the drawing of the figures is
greatly appreciated. This work was supported in part by Grants from the
Hungarian Science Foundation (OTKA NK-072661), the Hungarian Ministry of
Public Health (ETT 337/2009, ETT 318/2009),
TAMOP-4.2.1.B-09/1/KMR-2010-0001 and EU, LSHM-CT-2004-503474.
NR 89
TC 15
Z9 15
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD APR 28
PY 2012
VL 353
IS 1-2
SI SI
BP 29
EP 36
DI 10.1016/j.mce.2011.10.011
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 921YF
UT WOS:000302513300005
PM 22075205
ER
PT J
AU Majone, F
Jeang, KT
AF Majone, Franca
Jeang, Kuan-Teh
TI Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with
functional targeting of Ku80, not PKcs, XRCC4, or H2AX
SO CELL AND BIOSCIENCE
LA English
DT Article
DE HTLV-1; Tax; Ku80; PKcs; XRCC4; H2AX; DNA damage
ID DOUBLE-STRAND BREAKS; CELLULAR-TRANSFORMATION; GENE-EXPRESSION; DAMAGE
RESPONSE; REPAIR FACTORS; HISTONE H2AX; LIGASE-IV; ONCOPROTEIN;
INSTABILITY; INDUCTION
AB Background: Expression of the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein rapidily induces a significant increase of micronuclei (MN) and unstabilized DNA breaks in cells. Unstabilized DNA breaks can have free 3'-OH ends accessible to in situ addition of digoxygenin (DIG)-labeled dUTP using terminal deoxynucleotidyl transferase. In the present work, we used a GFP-Tax (green fluorescent protein) plasmid, which produces a functionally active GFP-tagged Tax protein, to detect the cellular target(s) for Tax which might mechanistically explain the clastogenic phenomenon. We examined the induction of MN and unstabilized DNA breaks in wild type cells and cells individually knocked out for Ku80, PKcs, XRCC4, and H2AX proteins. We also assessed in the same cells, the signal strengths produced by DIG-dUTP incorporation at the unstable DNA breaks in the presence and absence of Tax.
Results: Cells mutated for PKcs, XRCC4 and H2AX showed increased frequency of MN and unstabilized DNA breaks in response to the expression of Tax, while cells genetically mutated for Ku80 were refractory to Tax's induction of these cytogenetic effects. Moreover, by measuring the size of DIG-dUTP incorporation signal, which indicates the extent of unstable DNA ends, we found that Tax induces larger signals than those in control cells. However, in xrs-6 cells deficient for Ku80, this Tax effect was not seen.
Conclusions: The data here demonstrate that clastogenic DNA damage in Tax expressing cells is explained by Tax targeting of Ku80, but not PKcs, XRCC4 or H2AX, which are all proteins directly or indirectly related to the non-homologous end-joining (NHEJ) repair system. Of note, the Ku80 protein plays an important role at the initial stage of the NHEJ repair system, protecting and stabilizing DNA-breaks. Accordingly, HTLV-1 Tax is shown to interfere with a normal cellular protective mechanism for stabilizing DNA breaks. These DNA breaks, unprotected by Ku80, are unstable and are subject to erosion or end-to-end fusion, ultimately leading to additional chromosomal aberrations.
C1 [Majone, Franca] Dept Biol, I-35131 Padua, Italy.
[Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Majone, F (reprint author), Dept Biol, Via Bassi 58-B, I-35131 Padua, Italy.
EM franca.majone@unipd.it
FU Ministry of Education, University and Research [60A06-5770, 60A06-1802];
NIAID; Intramural AIDS Targeted Antiviral Program (IATAP) from the
office of the Director, NIH
FX We thank Renzo Mazzaro and Matteo Simonetti for preparation of figures.
This study was in part supported by Ministry of Education, University
and Research grants No. 60A06-5770 and 60A06-1802 to FM. Work in KTJ's
laboratory is supported in part by intramural funding from the NIAID and
from the Intramural AIDS Targeted Antiviral Program (IATAP) from the
office of the Director, NIH.
NR 31
TC 7
Z9 7
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD APR 27
PY 2012
VL 2
AR 15
DI 10.1186/2045-3701-2-15
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 011ZT
UT WOS:000309205800001
PM 22541714
ER
PT J
AU Grimsby, JL
Porneala, BC
Vassy, JL
Yang, QH
Florez, JC
Dupuis, J
Liu, TB
Yesupriya, A
Chang, MH
Ned, RM
Dowling, NF
Khoury, MJ
Meigs, JB
AF Grimsby, Jonna L.
Porneala, Bianca C.
Vassy, Jason L.
Yang, Quanhe
Florez, Jose C.
Dupuis, Josee
Liu, Tiebin
Yesupriya, Ajay
Chang, Man-Huei
Ned, Renee M.
Dowling, Nicole F.
Khoury, Muin J.
Meigs, James B.
CA MAGIC Investigators
TI Race-ethnic differences in the association of genetic loci with HbA(1c)
levels and mortality in US adults: the third National Health and
Nutrition Examination Survey (NHANES III)
SO BMC MEDICAL GENETICS
LA English
DT Article
ID IRON-DEFICIENCY ANEMIA; HISPANIC WHITE ADULTS; HEMOGLOBIN A(1C);
CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; HUMAN GENOME; GLYCATED
HEMOGLOBIN; RACIAL-DIFFERENCES; PLASMA-GLUCOSE; A1C LEVELS
AB Background: Hemoglobin A(1c) (HbA(1c)) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA(1c)-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA(1c) and 3) association of SNPs with mortality.
Methods: We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05.
Results: RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA(1c) in NHW (beta = 0.012 HbA(1c) increase per risk allele, p = 0.04) and MA (beta = 0.021, p = 0.005) but not NHB (beta = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71).
Conclusion: At many HbA(1c) loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA(1c)-associated variants on HbA(1c) levels varied by race-ethnicity, but did not influence mortality.
C1 [Grimsby, Jonna L.; Porneala, Bianca C.; Vassy, Jason L.; Florez, Jose C.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Grimsby, Jonna L.; Vassy, Jason L.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Yang, Quanhe; Yesupriya, Ajay; Chang, Man-Huei; Ned, Renee M.; Dowling, Nicole F.; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
EM jmeigs@partners.org
OI Dupuis, Josee/0000-0003-2871-3603
FU American Diabetes Association Mentored Post-Doctoral Fellowship Award;
National Institute for Diabetes and Digestive and Kidney Diseases
(NIDDK) [R01 DK078616]; NIDDK [K24 DK080140]; NIDDK Research Career
Award [K23 DK65978]; Massachusetts General Hospital Physician Scientist
Development Award; Doris Duke Charitable Foundation Clinical Scientist
Development Award
FX The data are from the NHANES III Public Use and Genetic Data Sets
(http://www.cdc.gov/nchs/nhanes/genetics/genetic.htm). Supported by an
American Diabetes Association Mentored Post-Doctoral Fellowship Award
(Dr. Grimsby), National Institute for Diabetes and Digestive and Kidney
Diseases (NIDDK) R01 DK078616 (Dr Meigs), NIDDK K24 DK080140 (Dr Meigs),
NIDDK Research Career Award K23 DK65978 (Dr Florez), a Massachusetts
General Hospital Physician Scientist Development Award, and a Doris Duke
Charitable Foundation Clinical Scientist Development Award (Dr Florez).
The MAGIC Investigators are listed in the on-line supplement. We thank
Sekar Kathiresan MD, for assistance in obtaining the NHANES III DNA that
we used for genotyping, and Peter Shrader MS for analytic assistance.
NR 56
TC 17
Z9 18
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD APR 27
PY 2012
VL 13
AR 30
DI 10.1186/1471-2350-13-30
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 000GA
UT WOS:000308373300001
PM 22540250
ER
PT J
AU Keller, JM
Noben-Trauth, K
AF Keller, James M.
Noben-Trauth, Konrad
TI Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with
frequency-specific effects on the hearing spectrum of NIH Swiss mice
SO BMC GENETICS
LA English
DT Article
DE NIH Swiss; Sensorineural hearing loss; Quantitative trait loci analyses;
Tonotopy; DPOAE
ID QUANTITATIVE TRAIT LOCI; OUTER HAIR-CELLS; MOUSE MODEL; LOSS DFNA36;
BEETHOVEN; COCHLEA; MAP
AB Background: The mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations.
Results: We identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum.
Conclusions: This study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea.
C1 [Keller, James M.; Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA.
RP Keller, JM (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA.
EM kellerjm@nidcd.nih.gov
FU NIDCD
FX We would like to thank Dr. Larry Leamy for his assistance calculating
Principal Components and for helpful discussions regarding their use in
our analyses. We would also like to thank Steven Raft and Richard
Chadwick for their comments regarding this manuscript. This work was
supported by the Intramural Program of NIDCD.
NR 30
TC 4
Z9 4
U1 0
U2 0
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 APR 27
PY 2012
VL 13
AR 32
DI 10.1186/1471-2156-13-32
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 986RA
UT WOS:000307360700001
PM 22540152
ER
PT J
AU Bonar, SL
Brydges, SD
Mueller, JL
McGeough, MD
Pena, C
Chen, D
Grimston, SK
Hickman-Brecks, CL
Ravindran, S
McAlinden, A
Novack, DV
Kastner, DL
Civitelli, R
Hoffman, HM
Mbalaviele, G
AF Bonar, Sheri L.
Brydges, Susannah D.
Mueller, James L.
McGeough, Matthew D.
Pena, Carla
Chen, Debbie
Grimston, Susan K.
Hickman-Brecks, Cynthia L.
Ravindran, Soumya
McAlinden, Audrey
Novack, Deborah V.
Kastner, Daniel L.
Civitelli, Roberto
Hoffman, Hal M.
Mbalaviele, Gabriel
TI Constitutively Activated NLRP3 Inflammasome Causes Inflammation and
Abnormal Skeletal Development in Mice
SO PLOS ONE
LA English
DT Article
ID OSTEOCLAST DIFFERENTIATION; CIAS1 MUTATIONS; GROWTH-PLATE; TNF-ALPHA;
BONE; DISEASE; CELLS; CRYSTALS; INCREASE; COLLAGEN
AB The NLRP3 inflammasome complex is responsible for maturation of the pro-inflammatory cytokine, IL-1 beta. Mutations in NLRP3 are responsible for the cryopyrinopathies, a spectrum of conditions including neonatal-onset multisystem inflammatory disease (NOMID). While excessive production of IL-1 beta and systemic inflammation are common to all cryopyrinopathy disorders, skeletal abnormalities, prominently in the knees, and low bone mass are unique features of patients with NOMID. To gain insights into the mechanisms underlying skeletal abnormalities in NOMID, we generated knock-in mice globally expressing the D301N NLRP3 mutation (ortholog of D303N in human NLRP3). NOMID mice exhibit neutrophilia in blood and many tissues, including knee joints, and high levels of serum inflammatory mediators. They also exhibit growth retardation and severe postnatal osteopenia stemming at least in part from abnormally accelerated bone resorption, attended by increased osteoclastogenesis. Histologic analysis of knee joints revealed abnormal growth plates, with loss of chondrocytes and growth arrest in the central region of the epiphyses. Most strikingly, a tissue "spike" was observed in the mid-region of the growth plate in the long bones of all NOMID mice that may be the precursor to more severe deformations analogous to those observed in NOMID patients. These findings provide direct evidence linking a NOMID-associated NLRP3-activating mutation to abnormalities of postnatal skeletal growth and bone remodeling.
C1 [Bonar, Sheri L.; Grimston, Susan K.; Hickman-Brecks, Cynthia L.; Novack, Deborah V.; Civitelli, Roberto; Mbalaviele, Gabriel] Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63130 USA.
[Brydges, Susannah D.; Mueller, James L.; McGeough, Matthew D.; Pena, Carla; Chen, Debbie; Hoffman, Hal M.] Univ Calif San Diego, Div Allergy Immunol & Rheumatol, La Jolla, CA 92093 USA.
[Brydges, Susannah D.; Mueller, James L.; McGeough, Matthew D.; Pena, Carla; Chen, Debbie; Hoffman, Hal M.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Brydges, Susannah D.; Mueller, James L.; McGeough, Matthew D.; Pena, Carla; Chen, Debbie; Hoffman, Hal M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Ravindran, Soumya; McAlinden, Audrey] Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO USA.
[Kastner, Daniel L.] NHGRI, Med Genet Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA.
RP Bonar, SL (reprint author), Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63130 USA.
EM gmbalavi@DOM.wustl.edu
OI McAlinden, Audrey/0000-0001-8433-4224; Novack,
Deborah/0000-0001-7101-5582; Civitelli, Roberto/0000-0003-4076-4315
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
NIH [RO1-AI52430]; National Institutes of Health/Core Center for
Musculoskeletal Biology and Medicine [5 P30 AR057235]; Arthritis
National Research Foundation
FX This work was supported by the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, extramural grants NIH RO1-AI52430,
the 5 P30 AR057235 National Institutes of Health/Core Center for
Musculoskeletal Biology and Medicine and the Arthritis National Research
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 32
TC 25
Z9 25
U1 0
U2 2
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 APR 27
PY 2012
VL 7
IS 4
AR e35979
DI 10.1371/journal.pone.0035979
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TJ
UT WOS:000305336000095
PM 22558291
ER
PT J
AU Krejci, P
Aklian, A
Kaucka, M
Sevcikova, E
Prochazkova, J
Masek, JK
Mikolka, P
Pospisilova, T
Spoustova, T
Weis, M
Paznekas, WA
Wolf, JH
Gutkind, JS
Wilcox, WR
Kozubik, A
Jabs, EW
Bryja, V
Salazar, L
Vesela, I
Balek, L
AF Krejci, Pavel
Aklian, Anie
Kaucka, Marketa
Sevcikova, Eva
Prochazkova, Jirina
Masek, Jan Kukla
Mikolka, Pavol
Pospisilova, Tereza
Spoustova, Tereza
Weis, MaryAnn
Paznekas, William A.
Wolf, Joshua H.
Gutkind, J. Silvio
Wilcox, William R.
Kozubik, Alois
Jabs, Ethylin Wang
Bryja, Vitezslav
Salazar, Lisa
Vesela, Iva
Balek, Lukas
TI Receptor Tyrosine Kinases Activate Canonical WNT/beta-Catenin Signaling
via MAP Kinase/LRP6 Pathway and Direct beta-Catenin Phosphorylation
SO PLOS ONE
LA English
DT Article
ID WNT; INSULIN; FGFR3; LRP6; MUTATIONS; DYSPLASIA; MECHANISM; CANCER
AB Receptor tyrosine kinase signaling cooperates with WNT/beta-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/beta-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate beta-catenin at Tyr142, which is known to increase cytoplasmic beta-catenin concentration via release of beta-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct beta-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling.
C1 [Krejci, Pavel; Aklian, Anie; Wilcox, William R.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Krejci, Pavel; Kaucka, Marketa; Sevcikova, Eva; Prochazkova, Jirina; Masek, Jan Kukla; Mikolka, Pavol; Pospisilova, Tereza; Spoustova, Tereza; Kozubik, Alois; Bryja, Vitezslav; Vesela, Iva; Balek, Lukas] Masaryk Univ, Dept Anim Physiol & Immunol, Inst Expt Biol, Brno, Czech Republic.
[Krejci, Pavel; Kozubik, Alois; Bryja, Vitezslav] Inst Biophys AS CR, Dept Cytokinet, Brno, Czech Republic.
[Weis, MaryAnn] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
[Paznekas, William A.; Jabs, Ethylin Wang] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Wolf, Joshua H.; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Wilcox, William R.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA.
[Salazar, Lisa] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
RP Krejci, P (reprint author), Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
EM krejcip@sci.muni.cz
RI Prochazkova, Jirina/D-7528-2012; Kozubik, Alois/H-1954-2014; Krejci,
Pavel/I-4285-2014; Bryja, Vit?zslav/H-1925-2014; Masek, Jan/I-9029-2014;
OI Bryja, Vit?zslav/0000-0002-9136-5085; Kaucka,
Marketa/0000-0002-8781-9769; Krejci, Pavel/0000-0003-0618-9134
FU National Institutes of Health (NIH) [5P01HD022657-21A]; NIH GCRC
[M01-RR00425]; Ministry of Education, Youth and Sports of the Czech
Republic [MSM0021622430]; Grant Agency of the Czech Republic
[301/09/0587, 204/09/H058, 204/09/J030, 305/11/0752]; Winnick Family
Research Scholars award; EMBO
FX This work was supported by: National Institutes of Health (NIH)
5P01HD022657-21A, NIH GCRC Grant M01-RR00425 (www.nih.gov/); Ministry of
Education, Youth and Sports of the Czech Republic (MSM0021622430)
(www.msmt.cz/); Grant Agency of the Czech Republic (301/09/0587,
204/09/H058, 204/09/J030, 305/11/0752) (www.gacr.cz); Winnick Family
Research Scholars award (WRW) (www.winnickfamilyfoundation.com); and
EMBO Installation grant (VB) (www.embo.org). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 24
TC 54
Z9 56
U1 0
U2 20
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 APR 27
PY 2012
VL 7
IS 4
AR e35826
DI 10.1371/journal.pone.0035826
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TJ
UT WOS:000305336000063
PM 22558232
ER
PT J
AU Marzi, A
Yoshida, R
Miyamoto, H
Ishijima, M
Suzuki, Y
Higuchi, M
Matsuyama, Y
Igarashi, M
Nakayama, E
Kuroda, M
Saijo, M
Feldmann, F
Brining, D
Feldmann, H
Takada, A
AF Marzi, Andrea
Yoshida, Reiko
Miyamoto, Hiroko
Ishijima, Mari
Suzuki, Yasuhiko
Higuchi, Megumi
Matsuyama, Yukie
Igarashi, Manabu
Nakayama, Eri
Kuroda, Makoto
Saijo, Masayuki
Feldmann, Friederike
Brining, Douglas
Feldmann, Heinz
Takada, Ayato
TI Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman
Primate Model of Ebola Hemorrhagic Fever
SO PLOS ONE
LA English
DT Article
ID VIRUS INFECTION; DEPENDENT ENHANCEMENT; MARBURG VIRUSES; GLYCOPROTEIN;
EPITOPES; IDENTIFICATION; MECHANISMS; RNA; GP
AB Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.
C1 [Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
[Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Nakayama, Eri; Kuroda, Makoto; Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Igarashi, Manabu] Hokkaido Univ, Res Ctr Zoonosis Control, Div Bioinformat, Sapporo, Hokkaido, Japan.
[Saijo, Masayuki] Natl Inst Infect Dis, Dept Virol 1, Tokyo, Japan.
[Feldmann, Friederike] NIAID, Off Operat Management, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
[Brining, Douglas] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
RP Marzi, A (reprint author), NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
EM atakada@czc.hokudai.ac.jp
RI Igarashi, Manabu/F-6871-2012; YOSHIDA, Reiko/F-6883-2012; Suzuki,
Yasuhiko/F-6890-2012; Takada, Ayato/A-6679-2012
FU Japan Initiative for Global Research Network on Infectious Diseases
(J-GRID); Ministry of Education, Culture, Sports, Science and Technology
(MEXT); Japan Science and Technology Agency Basic Research Programs;
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX This work was supported by the Japan Initiative for Global Research
Network on Infectious Diseases (J-GRID) and the Global COE Program from
the Ministry of Education, Culture, Sports, Science and Technology
(MEXT), and a Grant-in-Aid for JSPS Fellows Japan. The work was further
supported by Japan Science and Technology Agency Basic Research
Programs. Funding was also provided by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 36
TC 61
Z9 65
U1 4
U2 33
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 APR 27
PY 2012
VL 7
IS 4
AR e36192
DI 10.1371/journal.pone.0036192
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TJ
UT WOS:000305336000150
PM 22558378
ER
PT J
AU Mendez-Rios, JD
Martens, CA
Bruno, DP
Porcella, SF
Zheng, ZM
Moss, B
AF Mendez-Rios, Jorge D.
Martens, Craig A.
Bruno, Daniel P.
Porcella, Stephen F.
Zheng, Zhi-Ming
Moss, Bernard
TI Genome Sequence of Erythromelalgia-Related Poxvirus Identifies it as an
Ectromelia Virus Strain
SO PLOS ONE
LA English
DT Article
ID EPIDEMIC ERYTHROMELALGIA; INFECTIOUS ECTROMELIA; CAUSATIVE AGENT; MOUSE
SERUM; VACCINIA; ANTIBODY
AB Erythromelagia is a condition characterized by attacks of burning pain and inflammation in the extremeties. An epidemic form of this syndrome occurs in secondary students in rural China and a virus referred to as erythromelalgia-associated poxvirus (ERPV) was reported to have been recovered from throat swabs in 1987. Studies performed at the time suggested that ERPV belongs to the orthopoxvirus genus and has similarities with ectromelia virus, the causative agent of mousepox. We have determined the complete genome sequence of ERPV and demonstrated that it has 99.8% identity to the Naval strain of ectromelia virus and a slighly lower identity to the Moscow strain. Small DNA deletions in the Naval genome that are absent from ERPV may suggest that the sequenced strain of Naval was not the immediate progenitor of ERPV.
C1 [Mendez-Rios, Jorge D.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mendez-Rios, Jorge D.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Martens, Craig A.; Bruno, Daniel P.; Porcella, Stephen F.] NIAID, Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Mendez-Rios, JD (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research; NIAID; NIH
FX The word was supported by the Division of Intramural Research, NIAID,
NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 1
Z9 1
U1 1
U2 4
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 APR 27
PY 2012
VL 7
IS 4
AR e34604
DI 10.1371/journal.pone.0034604
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TJ
UT WOS:000305336000013
PM 22558090
ER
PT J
AU Wong, KA
Wilson, J
Russo, A
Wang, L
Okur, MN
Wang, XR
Martin, NP
Scappini, E
Carnegie, GK
O'Bryan, JP
AF Wong, Katy A.
Wilson, Jessica
Russo, Angela
Wang, Li
Okur, Mustafa Nazir
Wang, Xuerong
Martin, Negin P.
Scappini, Erica
Carnegie, Graeme K.
O'Bryan, John P.
TI Intersectin (ITSN) Family of Scaffolds Function as Molecular Hubs in
Protein Interaction Networks
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; CLATHRIN-MEDIATED ENDOCYTOSIS; BIMOLECULAR
FLUORESCENCE COMPLEMENTATION; ADAPTER PROTEIN; SIGNALING PATHWAYS; EPS15
HOMOLOGY; BINDING; MEMBRANE; DOMAINS; DYNAMIN
AB Members of the intersectin (ITSN) family of scaffold proteins consist of multiple modular domains, each with distinct ligand preferences. Although ITSNs were initially implicated in the regulation of endocytosis, subsequent studies have revealed a more complex role for these scaffold proteins in regulation of additional biochemical pathways. In this study, we performed a high throughput yeast two-hybrid screen to identify additional pathways regulated by these scaffolds. Although several known ITSN binding partners were identified, we isolated more than 100 new targets for the two mammalian ITSN proteins, ITSN1 and ITSN2. We present the characterization of several of these new targets which implicate ITSNs in the regulation of the Rab and Arf GTPase pathways as well as regulation of the disrupted in schizophrenia 1 (DISC1) interactome. In addition, we demonstrate that ITSN proteins form homomeric and heteromeric complexes with each other revealing an added level of complexity in the function of these evolutionarily conserved scaffolds.
C1 [Wong, Katy A.; Wilson, Jessica; Russo, Angela; Wang, Li; Okur, Mustafa Nazir; Wang, Xuerong; Carnegie, Graeme K.; O'Bryan, John P.] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60680 USA.
[Wong, Katy A.; Wilson, Jessica; Russo, Angela; Okur, Mustafa Nazir; Wang, Xuerong; O'Bryan, John P.] Univ Illinois, Coll Med, Cardiovasc Res Ctr, Chicago, IL USA.
[Wong, Katy A.; Wilson, Jessica; Russo, Angela; Okur, Mustafa Nazir; Wang, Xuerong; O'Bryan, John P.] Univ Illinois, Coll Med, UIC Canc Ctr, Chicago, IL USA.
[Okur, Mustafa Nazir] Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL USA.
[Martin, Negin P.; Scappini, Erica] NIEHS, Neurobiol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Wong, KA (reprint author), Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60680 USA.
EM obryanj@uic.edu
OI Martin, Negin/0000-0003-3166-8989
FU Foundation Jerome Lejeune; American Heart Association [11SDG5230003];
National Institutes of Health; National Institutes of Health [HL090651];
Department of Defense [PR080428]; St. Baldrick's Foundation
FX KAW was supported by a grant from the Foundation Jerome Lejeune, and LW
and GKC were supported by an American Heart Association grant
(11SDG5230003). These studies were supported by funds from the
intramural research program of the National Institutes of Health (JPO)
and by grants to JPO from the National Institutes of Health (HL090651),
Department of Defense (PR080428), the Foundation Jerome Lejeune, and the
St. Baldrick's Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 16
Z9 18
U1 0
U2 8
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 APR 27
PY 2012
VL 7
IS 4
AR e36023
DI 10.1371/journal.pone.0036023
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TJ
UT WOS:000305336000102
ER
EF